2015.08.28 02:22 Earthsophagus All the books in Lectures on Literature spoiled
2018.10.31 03:31 AnderLouis_ The Hemingway List
2009.07.07 15:00 noroom I Took a Picture: Give and get feedback on photography
2024.05.13 07:32 WDKilpackIII Epic Fantasy - Crown Prince: Book One of New Blood - W.D. Kilpack III
2024.05.13 01:28 greenlightxo Join our classic literature-themed book club
2024.04.25 10:32 Tiefblick Call for collaborators on fantasy manga art with aesthetic, moral and intellectual value / manifesto for better fiction
Popular entertainment (most fantasy & manga) | Art for the 21st century (golden mean) | Contemporary high art (Staubkunst1 et al.) |
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Take: - Outward form - Strong means - Vernal spirit | Gesamtkunstwerk Three pillars of creation: aesthetic, intellectual and moral aspiration Holistic art, integrating all attainable domains of human knowledge Aesthetics are paramount | Take: - Intellectual coherence - Deliberate proportions - Ethical responsibility |
- Unsophisticated, dumb humour, incoherent plots - Kitsch, i.e. excessive use of strongly evocative means for trivial purposes - Morally blind, reproducing flawed social norms | <-- current state of these | - Experimental, focussed on novelty rather than the big picture - Hyper-individualist, not appealing to the general population - Lost in semantics, i.e. overly focussed on (often political) statements rather than art for the sake of beauty |
Works | My thoughts on these |
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Manga & Anime: | |
Ghibli movies | enormous aesthetic value and moral insight, intellectually somewhat lacking (but made primarily for children) |
Tenshi no Tamago | aesthetically deep and intellectually curious, addressing the spiritual struggle of human existence in a bleak world, raising questions of faith, truth and illusion |
Angel Sanctuary | a just and beautiful reckoning with immoral societal purity codes around incest, curious exploration of gender norms |
Ghost in the Shell | aesthetically and somewhat intellectually impressive, asking deep questions related to the interaction of the “self” with technology and the future of consciousness |
Neon Genesis Evangelion (finale) | intellectually stimulating via fundamental philosophical questions raised regarding human togetherness, aesthetically stimulating use of Western classical music |
The opening of Elfen Lied | pretty artworks inspired by Gustav Klimt accompanied by a beautiful song inspired by Gregorian chant |
Selected hentai, yaoi, doujinshi and furry porn works | exemplifying the purely aesthetic insights found in sexual fiction |
Literature: | |
J.R.R. Tolkien’s legacy, including the Silmarillion, Hobbit and Lord of the Rings | deeply aesthetic and rich in moral wisdom (though with moral flaws owed to his time), intellectually meaningful by exploring philology in fiction |
Video Games: | |
Shadow of the Colossus | deeply aesthetic, evoking primal drives and intense natural and architectural beauty |
Guild Wars 2 | very beautiful in terms of landscapes and architecture, but intellectually unsophisticated and morally clueless |
Planescape Torment | proves that philosophy may be a fruitful basis for a fantasy video game, intellectually and aesthetically uniquely rewarding |
Baldur’s Gate | comparatively high literary standard for a fantasy video game, beautiful hand-drawn artworks, somewhat rich cultural basis thanks to D&D lore and some philosophically interesting themes |
The Elder Scrolls 3: Morrowind | rich in cultural aesthetics, interesting treatment of colonial history and its socio-political implications in a fantasy setting, unique landscape design |
Music: | |
Jeremy Soule | captures the beauty of landscapes and the joy of traveling (fictional worlds) |
2024.04.15 21:22 jefrye Recommending books based on “folklore”
[Reposting because formatting issues, and the images mean I can't make edits...sorry mods!] submitted by jefrye to TaylorSwift [link] [comments] Hi everyone! Reading is my main hobby, and in anticipation of “The Tortured Poets Department,” I wanted to share a list of (spoiler-free) book recommendations based on my favorite albums of all time by any artist: folklore and evermore. (This got long so evermore will be a separate post.) Both albums just feel very literary to me (probably a big reason why I love them so much), and even on first listen immediately reminded me of some of my favorite books. Since then, it’s been impossible not to make more connections with what I’ve been reading. I thought it would be fun to put together a list with recommendations for every track, and here it is! I tried to pick only books that I absolutely adore, so most of these are all-time favorites—but I also really wanted to go with books that felt like they matched the tracks, so a few less-than-favorites slipped through (though none that I actively dislike, except as honorable mentions). I picked books not necessarily because they match the exact “plot” of a given song, but because they might resonate with a lyric, or a theme, or the overall ~vibe~. For each one, I picked out a lyric that matches well, and then I also have a “similarities” section to explain what I think they have in common. In a few cases, the recommendations are literally perfect plot-wise, but I won’t tell you if it gives away a twist (I hate spoilers so I’m keeping this spoiler-free! I’m also not listing trigger warnings, in part because they can be spoiler-y, but mostly because I don’t remember everything that happens in each of these books well enough to ensure that I’m being thorough.). I’d love to hear if any other readers have recommendations of their own! Or, if you’ve read any of these, I’d be curious to know if you agree with my track pairing :) the 1In my defense, I have none / For never leaving well enough alonehttps://preview.redd.it/b9cfekqg1puc1.jpg?width=286&format=pjpg&auto=webp&s=580ec7b9115f6e8a75f4b675c51f4a941100fa3e Recommendation: Excellent Women by Barbara Pym Mildred Lathbury is one of those ‘excellent women’ who is often taken for granted. She is a godsend, ‘capable of dealing with most of the stock situations of life – birth, marriage, death, the successful jumble sales, the garden fete spoilt by bad weather’. As such, she often gets herself embroiled in other people’s lives – especially those of her glamorous new neighbours, the Napiers, whose marriage seems to be on the rocks. One cannot take sides in these matters, though it is tricky, especially as Mildred, teetering on the edge of spinsterhood, has a soft spot for dashing young Rockingham Napier.Similarities: Contemporary, upbeat, undercurrents of melancholy, themes of self-acceptance and quiet contentment Review: Very funny and a little sad, a bit like if Jane Austen wrote about a 30-something spinster who resigned herself to never marrying and was instead involved in everyone else’s business. Character-focused without much of a plot, but who needs a plot when you have an author like Pym. Honorable mention(s):
cardiganYou put me on and said I was your favoritehttps://preview.redd.it/atytz16h1puc1.jpg?width=292&format=pjpg&auto=webp&s=fdf5fcde5c547ff910a31c010cd52819d285f451 Recommendation: Madame Bovary by Gustave Flaubert (translated by Adam Thorpe) Emma Bovary is an avid reader of sentimental novels; brought up on a Normandy farm and convent-educated, she longs for the passion of romance. At first, Emma pins her hopes on marriage, but life with her well-meaning husband in the provinces leaves her bored and dissatisfied. She seeks escape through extravagant spending sprees and, eventually, adultery. As Emma pursues her impossible reverie she seals her own ruin and despair. Exquisite, moving, at times ferociously satirical and always psychologically acute, Madame Bovary remains one of the greatest, most beguiling novels ever written.Similarities: Whirling/spinning feeling, romantic, cozy, autumnal, dark, the eponymous Madame Bovary would absolutely identify with all the lyrics Review: Some of the most beautiful writing I’ve ever read: it feels cinematic, dreamlike, decadent, opulent, glamorous, gilded…in short, everything that Emma wants her life to be like. I knew how it would end but I was unprepared. Honorable mention(s):
the last great american dynastyShe had a marvelous time ruining everythinghttps://preview.redd.it/804s6d5i1puc1.jpg?width=298&format=pjpg&auto=webp&s=8201706e19a3185c1e1d5dd71029a460967353c9 Recommendation: Gone with the Wind by Margaret Mitchell Set against the dramatic backdrop of the American Civil War, Margaret Mitchell's magnificent historical epic is an unforgettable tale of love and loss, of a nation mortally divided and a people forever changed. Above all, it is the story of beautiful, ruthless Scarlett O'Hara and the dashing soldier of fortune, Rhett Butler.Similarities: Fast-paced, upbeat, precocious; featuring glamorous, devil-may-care women who cause an uproar Review: We all know it’s racist (the characters, which would be completely excusable, but also the book itself, which is the ~problematic~ part), but that doesn’t mean it’s not also brilliant and unbelievably entertaining. Almost every character is utterly despicable and it’s a thousand pages long, but the book’s impossible to put down. Honorable mention(s):
exile (feat. bon iver)I can see you starin', honey / Like he's just your understudy / Like you'd get your knuckles bloody for mehttps://preview.redd.it/6pbs7m9k1puc1.jpg?width=323&format=pjpg&auto=webp&s=4d6bd8ab44ae6cebd25b2b818b09d22f81c21455 Recommendation: Wuthering Heights by Emily Brontë Wuthering Heights is the tale of two families both joined and riven by love and hate. Cathy is a beautiful and wilful young woman torn between her soft-hearted husband and Heathcliff, the passionate and resentful man who has loved her since childhood. The power of their bond creates a maelstrom of cruelty and violence which will leave one of them dead and cast a shadow over the lives of their children. Emily Brontë's novel is a stunningly original and shocking exploration of obsessive passion.Similarities: gothic, dramatic, dark, cold, violent, obsessive, passionate; themes of jealousy and broken hearts Review: Wuthering Heights seems to be a love-it-or-hate-it kind of novel…and I love it, though it’s undeniably bizarre and populated by completely unlikeable characters. The atmosphere is incredible. The framing device and character names are confusing but they’re (mostly) supposed to be, so I always warn new readers that if you feel lost in the beginning it’s not you, it’ll all make sense when Emily wants it to. Honorable mention(s):
my tears ricochetIf I'm on fire, you'll be made of ashes too.https://preview.redd.it/t56y9hnk1puc1.jpg?width=291&format=pjpg&auto=webp&s=d697ef3443337ba29881b4b33e719e92995c36be Recommendation: The Count of Monte Cristo by Alexandre Dumas (translated by Robin Buss) Thrown in prison for a crime he has not committed, Edmond Dantès is confined to the grim fortress of If. There he learns of a great hoard of treasure hidden on the Isle of Monte Cristo and he becomes determined not only to escape, but also to unearth the treasure and use it to plot the destruction of the three men responsible for his incarceration. Dumas’ epic tale of suffering and retribution, inspired by a real-life case of wrongful imprisonment, was a hugely popular success when it was first serialized in the 1840s.Similarities: Vengeful, tragic, sweeping, a little melodramatic Review: The first section of the novel will always be my favorite, but the entire thing is a fantastically fun adventure. It’s a doorstopper, but so plot-heavy that I don’t recommend an abridgement. Honorable mention(s):
mirrorballI know they said the end is near / But I'm still on my tallest tiptoes / Spinning in my highest heels, love / Shining just for you.https://preview.redd.it/ltdi3g6l1puc1.jpg?width=294&format=pjpg&auto=webp&s=1ca7523514adeeb970992dbef45584c98159f48a Recommendation: The Night Circus by Erin Morgenstern The circus arrives without warning. No announcements precede it. It is simply there, when yesterday it was not. Within the black-and-white striped canvas tents is an utterly unique experience full of breathtaking amazements. It is called Le Cirque des Rêves, and it is only open at night.Similarities: Magical, glittering, romantic, atmospheric, vintage, dreamlike, fragile, slow Review: This novel is all about atmosphere—the plot is somewhat underwhelming and the characters are thin—but what an atmosphere it is. Morgenstern’s writing dazzles and enchants, and the love story is deeply romantic. Honorable mention(s):
sevenAnd I've been meaning to tell you / I think your house is hauntedhttps://preview.redd.it/ccq50pwl1puc1.jpg?width=300&format=pjpg&auto=webp&s=0d654e79fb42c5f93aef81e98398ee708d959e55 Recommendation: The Ocean at the End of the Lane by Neil Gaiman A middle-aged man returns to his childhood home to attend a funeral. Although the house he lived in is long gone, he is drawn to the farm at the end of the road, where, when he was seven, he encountered a most remarkable girl, Lettie Hempstock, and her mother and grandmother. He hasn't thought of Lettie in decades, and yet as he sits by the pond (a pond that she'd claimed was an ocean) behind the ramshackle old farmhouse, the unremembered past comes flooding back. And it is a past too strange, too frightening, too dangerous to have happened to anyone, let alone a small boy.Similarities: Bright, glittery, idyllic, nostalgic, whimsical, dreamlike, wistful, innocent, trusting, a little bit melancholy Review: The writing is beautiful and charming and the story itself is strangely compelling; it has an almost mythical feel to it, a bit like a fairytale for adults (even though the main character is a child for most of it). I think I will probably like this more when I reread it, now that I know what to expect; I was expecting something a bit more adult, more on the realism side of magical realism... But I still really liked it. Honorable mention(s):
augustBack when I was living for the hope of it allhttps://preview.redd.it/5imt3yem1puc1.jpg?width=286&format=pjpg&auto=webp&s=38b4a377400f33933d7152af67de8786baaf5849 Recommendation: The Bell Jar by Sylvia Plath The Bell Jar chronicles the crack-up of Esther Greenwood: brilliant, beautiful, enormously talented, and successful, but slowly going under—maybe for the last time. Sylvia Plath masterfully draws the reader into Esther's breakdown with such intensity that Esther's insanity becomes completely real and even rational, as probable and accessible an experience as going to the movies. Such deep penetration into the dark and harrowing corners of the psyche is an extraordinary accomplishment and has made The Bell Jar a haunting American classic.Similarities: Long summer days, sweltering heat, getting caught up in the moment, a twinge of sadness; “It was a queer, sultry summer, the summer they electrocuted the Rosenbergs, and I didn't know what I was doing in New York" Review: Plath’s prose is incredibly evocative and compelling, and I was completely caught up in Esther’s psyche. It’s not something I’d reread due to the subject matter, but I couldn’t put it down and would recommend it to those interested in psychological, sometimes disturbing character studies. this is me tryingIt's hard to be anywhere these days when all I want is youhttps://preview.redd.it/wn71ga2n1puc1.jpg?width=326&format=pjpg&auto=webp&s=16642a92ea091b236f0188e018691e01144df3f5 Recommendation: Jane Eyre by Charlotte Brontë As an orphan, Jane's childhood is full of trouble, but her stubborn independence and sense of self help her to steer through the miseries inflicted by cruel relatives and a brutal school. A position as governess at the Thornfield Hall promises a kind of freedom. But Thornfield is a house full of secrets, its master a passionate, tormented man, and before long Jane faces her greatest struggle in a choice between love and self-respect.Similarities: Nostalgic, dark, vulnerable, layered, slow Review: I love this book. It has a few slow places, but it’s very easy to read and, in the true spirit of a gothic romance, filled with several truly insane twists. I think it would be a great starting place for someone looking to get into Victorian or classic literature. Honorable mention(s):
illicit affairsYou showed me colors you know / I can't see with anyone elsehttps://preview.redd.it/ez4bxrmn1puc1.jpg?width=292&format=pjpg&auto=webp&s=cf7fec67ca42925dce7acf51e7eb2bf6b8979364 Recommendation: Two on a Tower by Thomas Hardy Lady Constantine breaks all the rules of decorum when she falls in love with beautiful youth Swithin St Cleeve, her social inferior and ten years her junior. Together, in an ancient monument converted into an astronomical observation tower, they create their own private universe - until the pressures of the outside world threaten to destroy it.Similarities: Messy, tragic, beautiful, sparkly, clandestine romance Review: I loved the writing style, atmosphere, and setting—as a kid I went through a phase of wanting to be an astronomer, and it never fully wore off. However, I will say that the characters are incredibly one-dimensional, the age gap is horrifying, and the ending is very bad (laughably so)....but come on, they fall in love on an astronomy tower. Can it get any more romantic than that? Honorable mention(s):
invisible stringTime, curious time / Gave me no compasses, gave me no signs / Were there clues I didn't see?https://preview.redd.it/g9d4yl5o1puc1.jpg?width=300&format=pjpg&auto=webp&s=1b93c1d830c67388c9312d84d9af54fe4c72ead6 Recommendation: Piranesi by Susanna Clarke Piranesi's house is no ordinary building: its rooms are infinite, its corridors endless, its walls are lined with thousands upon thousands of statues, each one different from all the others. Within the labyrinth of halls an ocean is imprisoned; waves thunder up staircases, rooms are flooded in an instant. But Piranesi is not afraid; he understands the tides as he understands the pattern of the labyrinth itself. He lives to explore the house.Similarities: Whimsical, childlike, fateful, optimistic, lighthearted Review: A perfect little puzzle of a book. I won’t say much because a large part of the joy of reading it the first time is in trying to unravel the mysteries within, but suffice to say that it’s a delightful, enchanting novel that’s nearly impossible to put down (and WOW Clarke nails character voice). Honorable mention(s):
mad womanYou made her like thathttps://preview.redd.it/3ufpmgpo1puc1.jpg?width=297&format=pjpg&auto=webp&s=63adc7cbeb66c28e947f816d868b1718d90d25f6 Recommendation: Gone Girl by Gillian Flynn Who are you? What have we done to each other?Similarities: Dark, poetic, bitter, vengeful….I can't explain my thought process without spoiling it Review: This is one of the only books on the list that I haven’t read/reread in the last few years, but I loved it in college. Flynn’s writing is equal parts beautiful and razor sharp, and she clearly has a lot to say. The big reveal definitely took me by surprise. (The movie is a faithful adaptation, so if you’ve seen it you already know the whodunnit.) In my opinion this really straddles the line between mystery and literary fiction. Honorable mention(s):
epiphanyJust one single glimpse of relief / To make some sense of what you've seenhttps://preview.redd.it/17lbnz4p1puc1.jpg?width=295&format=pjpg&auto=webp&s=b341c05a23885dcdb2b3722195256830aca155a8 Recommendation: All the Light We Cannot See by Anthony Doerr Marie-Laure lives in Paris near the Museum of Natural History, where her father works. When she is twelve, the Nazis occupy Paris and father and daughter flee to the walled citadel of Saint-Malo, where Marie-Laure’s reclusive great uncle lives in a tall house by the sea. With them they carry what might be the museum’s most valuable and dangerous jewel.Similarities: Quiet, ethereal, haunting, beautiful, tragic; war as a theme Review: Another book that I haven’t read in years; I liked it, but it’s not a favorite. At the time I remember struggling to connect to the characters or feel emotionally engaged; I expect I’d like it even less if I read it today due to how heavily romanticized and at times melodramatic I remember it being, which I've become more critical of as I've read more and gotten older. (If I wanted to be really mean I’d say it’s like if Hallmark set out to make a serious, romanceless war movie.) But the writing is undeniably beautiful. (Haven’t seen the Netflix series.) Honorable mention(s): All Quiet on the Western Front by Erich Maria Remarque: An infinitely better war novel, in part because it’s not romanticized (it’s pretty brutal), but that also means the tone doesn’t fit the song. This is the one I would actually recommend if I wasn't set on sticking to my rules for this list. bettyBut if I just showed up at your party / Would you have me? Would you want me?https://preview.redd.it/21yt91op1puc1.jpg?width=260&format=pjpg&auto=webp&s=2ce5a3dfc757f93a13460079797c543225df0f7f Recommendation: Anne of Green Gables by L. M. Montgomery When Anne Shirley "erupts" into the Cuthberts's lives, they don't realize how fond they will become of the red-haired orphan. Both entertained and exasperated by her constant chatter and imaginings, they soon find it hard to remember what Green Gables was like without its adopted daughter.Similarities: Unembellished, candid, unconventional, straightforward, bright, clean Review: I cried, I laughed, and I was thoroughly enchanted by Anne. I read them all as a kid and plan to reread them all soon (this is the only one I've gotten to so far). Honorable mention(s):
peaceOur coming-of-age has come and gone / Suddenly the summer, it's clear / I never had the courage of my convictionshttps://preview.redd.it/hj81ow4q1puc1.jpg?width=268&format=pjpg&auto=webp&s=dfed117d7aaf75f76d4cc0f48b84a969af751210 Recommendation: The Blue Castle by L.M. Montgomery At twenty-nine, Valancy has never been in love, and it seems romance has passed her by. Living with her overbearing mother and meddlesome aunt, she finds her only consolations in the forbidden books of John Foster and her daydreams of the Blue Castle. Then a letter arrives from Dr. Trent—and Valancy decides to throw caution to the winds. For the first time in her life Valancy does and says exactly what she wants. Soon she discovers a surprising new world, full of love and adventures far beyond her most secret dreams.Similarities: Tmid, cautious, wistful, romantic, placid; themes of doomed love, inadequacy, longing, dread, fear of being a burden; peace kind of sounds like being on a lake in the evening Review: Kind of over the top and ridiculous, but I love it anyway. Gorgeous nature writing and incredibly romantic, and has hidden depth when it comes to characterization. Honorable mention(s):
hoaxYou knew the hero died, so what's the movie for?https://preview.redd.it/8gf2f3jq1puc1.jpg?width=293&format=pjpg&auto=webp&s=77883759d558854e402e20e12e6a2fce5690f5f0 Recommendation: The Tenant of Wildfell Hall by Anne Brontë When a mysterious and beautiful young widow becomes the new tenant at Wildfell Hall, rumours immediately begin to swirl around her. Almost against his will, Gilbert Markham is drawn to the elusive and singular Helen Graham, but even as he falls in love, he finds himself divided from Helen by dark secrets and painful memories from her past life.Similarities: Quiet, broken down and broken-hearted, slow, regretful, lost love, widowhood Review: Absolutely incredible novel that is written in the most poetic language (primarily diary entries by Helen) and feels surprisingly modern. Avoid reading anything about it—including back-of-book blurbs, other descriptions on Goodreads, etc.—because almost all of them spoil the novel by revealing Helen’s secret, which is the end-of-book “twist.” the lakesWhat should be over burrowed under my skin / In heart-stopping waves of hurt.https://preview.redd.it/q5r0geyq1puc1.jpg?width=286&format=pjpg&auto=webp&s=7939b58bbdda9cac6f6bd445d7864f5f629752a1 Recommendation: Rebecca by Daphne du Maurier Last night I dreamt I went to Manderley again… Working as a paid companion to a bitter elderly lady, the timid heroine of Rebecca learns her place. Life is bleak until, on a trip to the South of France, she falls in love with Maxim de Winter, a handsome widower whose proposal takes her by surprise. Whisked from Monte Carlo to Manderley, Maxim's isolated Cornish estate, the friendless young bride begins to realise she barely knows her husband at all. And in every corner of every room is the phantom of his beautiful first wife, Rebecca. Rebecca is the haunting story of a woman consumed by love and the struggle to find her identity.Similarities: Romantic, poetic, picturesque, melodramatic, vintage, contemplative, undercurrents of sadness and tragedy Review: Talk about “calamitous love and insurmountable grief”… This is the best of gothic romance paired with the best of psychological suspense, and the result is brilliant. I think it’s impossible to read this and not be deeply emotionally affected, especially if you really read between the lines and pick up on the subtextual truths that the narrator refuses to admit. To top it off, it’s written in the most beautiful, poetic, hypnotic prose I’ve ever read. My favorite novel of all time. (None of the movies succeed in capturing the spirit of the novel; I think this is a novel that’s impossible to successfully adapt because it’s so interior.) Honorable mention(s):
Carolina(We can all agree this is part of the folkmore era, right?)Lost I was born, lonesome I came / Lonesome I'll always stayhttps://preview.redd.it/d47v0qks1puc1.jpg?width=300&format=pjpg&auto=webp&s=df52b19fcf9c9f8144ef6ef59c3a8cd6f40c1eab Recommendation: Annihilation by Jeff VanderMeer For thirty years, Area X has remained mysterious and remote behind its intangible border - an environmental disaster zone, though to all appearances an abundant wilderness. The Southern Reach, a secretive government agency, has sent eleven expeditions to investigate Area X. One has ended in mass suicide, another in a hail of gunfire, the eleventh in a fatal cancer epidemic. Now four women embark on the twelfth expedition into the unknown.***Similarities:***Haunting, atmospheric, nature writing, mysterious, kind of creepy Review: Absolutely amazing novel that’s primarily a character study of a woman who’s always felt more connected to nature than to other people. (I’ve seen and liked the movie, but they’re different.) Honorable mention(s):
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2024.04.12 12:46 Work-Live Advice on reading French literature in the original
2024.04.12 03:06 jedisalsohere Eighth Doctor Book Review #16 & 17: The Janus Conjunction and Beltempest
2024.04.11 21:12 cryinginthebenz Panoramic BestSellers By Re-Marks, 1000 pcs, glued and hung on wall !!
This was a super fun one and looks so cool by my ever growing bookshelf ✨ submitted by cryinginthebenz to Jigsawpuzzles [link] [comments] |
2024.04.10 23:54 CatsAndTrembling Greatest Book Published During Each Presidency (new, fixed version)
submitted by CatsAndTrembling to Presidents [link] [comments] |
2024.04.10 10:10 fsw820 I'm younger than that now: How did Game Science create Black Myth: Wukong (Original URL: https://www.bilibili.com/read/cv7260925/)
https://preview.redd.it/6ft4zsnazltc1.png?width=865&format=png&auto=webp&s=52e4febaa7155f26a297b87e802a49349f5fda16 submitted by fsw820 to BlackMythWukong [link] [comments] At 7pm on August 20, I went to a cinema in Hangzhou. Before the movie starts, a trailer for Black Myth: Wukong will be shown in the cinema. \Editor Zhu jiayin* (posted on August 20, 2020 at 16:00) *Chuapp(a Chinese media about games:https://www.chuapp.com/) Prologue February 25, 2018. Feng Ji flew back to Shenzhen from Shanghai. It was evening when he arrived in Shenzhen, and Feng Ji took a taxi back to his company from the airport. On the way back to work, he decided it was time to make a decision. ^((\Game Science have two studios, one in Shenzhen and the other in Hangzhou)*) Feng Ji called the other partners and asked them to come to the company for a meeting to discuss what to do next. At 2 o 'clock in the morning, Feng Ji wrote down three roads for everyone on the whiteboard in the conference room. "The first path is for everyone to concentrate on making a single-player action game; The second path is to make a popular RPG+SLG mobile game; The third way is to divide into two teams, one team to do mobile games, and five or six people(another team)are ready to do a single-player action game." Everyone took the third option. Before receiving Feng Ji's phone call, Yang Qi sent a microblog(like a tweet). He knew what Feng Ji was going to say, and he was waiting for the call. He wrote on his microblog: "The New Year begins to do something crazy, and 10 years in the gaming industry seems to be waiting for this day. I went out for a meeting in the midnight, and the trees of the whole community were whispering my name..." Yang Qi posted such a microblog that day 1 I was sitting in Feng Ji's office on August 16, 2020, listening to him tell me the above story. Then he thought for a moment and told me that the 2 a.m. meeting wasn't really a "turning point." "It's really not that dramatic." Feng Ji told me, "We have discussed this for a long time. And I was looking through the business plan we wrote when we were financing in 2016, you know? To write this thing for Financing, I looked the plan, found that there is a third of the content to write that we are going to do a single-player video game——I have now forgotten, and then I went to check the chat history... It really is." Feng Ji is the founder of Game Science studio. In 2014, Mr. Feng and several of his longtime colleagues who had created Asura left Tencent to form Game Science. ^((\Asura: 斗战神.)* *It literally means “god of fighting”, which is very close to “Victorious Fighting Buddha”, the title Wukong was awarded after finishing his journey. It’s a MMORPG they made at Tencent, also based on Journey to the West, but the style was too young and radical, and the beginning was good, but the follow-up update went wrong*) Several of the early works of Game Science were fashionable at the time. Yang Qi's art style is aamazing and prominent, and Feng Ji knows how to make the game more stylish. Their strategy is to find the most popular genres of games on the market, plus top-notch art, worldview, and stories. "100 heroes" is a card game, and "Red Tides" is an RTS, and Red Tides auto-chess...... It is an auto-chess. When the project was first launched, the auto-chess theme was in full swing, and the number of people online in the game was good, but after that, auto-chess seemed to be suddenly forgotten, and all the auto-chess game data was declining, and so were theirs. (*100 heroes and Red Tides: their mobile games**)** The character design of \"100 heroes\" is very cool In November 2017, two months after the open beta of "Red Tide", the company's partners felt that RPG+SLG seemed to be a project that could make money quickly. So they started making an RPG+SLG type game. The new game follows the worldview of Red Tides and uses the universe as a battlefield. Feng Ji is the chief planner of the game, and Yang Qi, the co-founder of Game Science, is the art director. By the beginning of 2018, Yang Qi had drawn a lot of concept drawings for this new game, and Feng Ji had already done some preliminary design. But Feng Ji didn't see anything interesting on this game. "I can't stand it anymore - you know what I mean, right?" Feng Ji said to me, "I can't stand it, which means that I don't really want to play this game." "Although we all think that sooner or later we will begin our single-player video game, sooner or later, we always feel that the time is not ripe, and we always feel that it is not the right time, for example, we don't have enough money, or ...... Anyway, we just want to wait for a moment.“ Feng Ji explained. But Yang Qi didn't want to wait any longer. "Once at dinner, Yang Qi resolutely proposed that the single-player video game must start now. Feng Ji told me, "He(Yang Qi)said that you can always find a reason not to start——there is not enough money / not enough people / conditions in all kinds are insufficient...... If you wait like this, you may never start. But he felt that if he didn't, the company might not be attractive enough to him...... So, we started to talk about it in earnest.” That afternoon, I met Yang Qi in Feng Ji's office. Compared to Feng Ji, his state seems calm and detached, and he seems to be accustomed to detaching himself and evaluating himself and the whole thing from the perspective of a third party. He pulled his mask down to his chin and smoked a cigarette with a fruity popping bead. We talked while smoking. I asked Yang Qi why he was so resolute in this matter, he said very easily: "We also waited for a while, we have made some other games, you know, you must live first." I asked him the question again. He thought about it for a moment, then told me seriously, "Because I don't think I can work like this for a few years...... My body couldn't bear it. For example, I used to rotate for several days without weariness, but now I have to sleep after staying up all day. Moreover, people's creative life is limited, and a person's golden time for creation may only be a few years, when you have experience, physical strength, and flexible brains...... This is your most precious time, and if you don't create something good at this time, you may never get another chance in this life......" After deciding to play a single-player video game, Yang Qi was "obviously in high spirits". At that time, Game Science didn't have their Hangzhou studio, and all the developers were working on the second floor of the Shenzhen office, and after that meeting, they vacated a small corner of the first floor for the project, and Yang Qi moved down the next day. This made Feng Ji feel very good. As the founder of Game Science, he felt a responsibility to the other "people who came out with him". He also wants to see his friends at work in high spirits——even just in high spirits. 2. Game Science's Hangzhou studio is located in an entrepreneurial industrial park on the outskirts of Hangzhou. The Pioneer Park is newly built, and there are small buildings in the Hui stylescattered in the park, with white walls and black tiles. I walked into the park on a hot summer afternoon, almost all the houses were empty probably because the COVID-19 is not over yet. There are some workers who are maintaining the roads. Game Science's new office in Hangzhou "Originally, it was said that there was Starbucks or something, but because of the COVID-19, it has not yet been settled.” Feng Ji said, pointing to a house in front of him which was obviously unopened. ^((\Hui style:)* 徽派风格. *It refers to the ancient architectural style of Anhui and Zhejiang provinces, mainly with wooden frames, white walls and green tiles, elegant and exquisite, with exquisite carvings*) Game Science has a small four-story building here. It was about 2 P.M. when I went, and their day was just getting started. Lights were off in the room, and almost everyone was lazily slumped in their chairs, looking like they were going to fall asleep at any moment. There are either animations or gameplay videos on the screen, or some unintelligible but cool interface. All of the windows had no curtains, and some had a few pieces of cardboard glued to them with scotch tape to keep them out of direct sunlight. "I haven't had time to install the curtains yet. Feng Ji led me upstairs. The second floor is a common area, with several treadmills and bicycles in the corner, and some tables and chairs in the middle. The third floor is empty, with a 70-inch monitor on the wall, and a few wooden knives and two shields in the corner. Feng Ji told me that they will do a preliminary inertial motion capture here, which will serve as a reference for the next step of more detailed optical motion capture. The fourth floor is his office, but he says he doesn't often stay upstairs. The single-player game team moved to Hangzhou in December 2018. Feng Ji likes the atmosphere of Hangzhou, the pace here is not as fast as Shenzhen, and the housing prices are not too high. As a relatively mature development company with sufficient development experience, Game Science avoids most of the risks in the game development process. Their core creative team have worked together for many years and know each other's abilities. They are familiar with the game development process and have experience developing successful games. They have always controlled the size of the project and have always maintained a very small team with a lot of experience and tacit understanding. In the beginning, there was no objection to what to do. By default, everyone wants to make an action game with weak network, focusing on combat experience, and fighting with cold weapon. Of course, there is a debate about the specific style, but the general direction has not changed. They talk every day, when they eat, and when they are at workstations. The style of the game, the character traits and a lot of details slowly form a consensus. At that time, Feng Ji was obsessed with "Dark Souls", and Yang Qi preferred "Monster Hunter", and the consensus was to make an action game with "a very strong sense of enemy oppression", "exquisite level structure", and "fragmented narrative with a mysterious style". Prior to this, the engines used by Game Science were Cocos and Unity, and the common characteristics of these two engines were simplicity and low learning cost. When it comes to new projects, the best option is Unreal. So everyone started learning the Unreal engine from scratch. Feng Ji learns how to move the camera, Yang Qi tries to build the scene and adjust the lighting, and another planner, the "village chief"(Jiang Baicun, Lead Game Designer), begins to build a white box, "where to set up blocks, how to paint the air wall". In May 2018, the pre-research team built the first basic scene to experiment with the most basic sense of fighting, AI and combo feel. Once successful, they decided to start experimenting with an experimental level that would show off the "final effect". They chose Huaguo Mountain. You'll see a scene in yesterday's(August 20, 2020)13-minute video of Black Myth: Wukong, where the protagonist walks by cloud, accompanied by a loong, and the background is a densely vegetated mountain peak, which is Huaguo Mountain. ^((\Huaguo Mountain:)* ***花果山****. It literally means mountain which was full filled with plants and fruits. It is where Sun Wukong was born, at the beginning of the story, Wukong became the king of the mountain, and here that he fought against the heavenly army when the Jade Place decided to wipe out his force.*) ^((\Loong: 龙.)* *The divine animal of China, totally different from dragon. The Loong in 2021 video Game Science released is a typical one*) Huaguo Mountain scene in the demo At the end of 2018, the Huaguo Mountain level was basically formed, and they realized the basic game functions. The protagonist was born and walked out of the cave——the Heavenly Soldiers are besieging Huaguo Mountain, the protagonist moves forward in battle, fights with a Heavenly General, and after the battle, the protagonist rises to the clouds and fights against the Heavenly army under the gaze of The Four Heavenly Kings. ^((\The Four Heavenly Kings: 四大天王.)* *The four protector gods in Chinese mythology, each with an unique weapon and appearance, guarding the four heavenly gates in the east, west, north and south*) "100,000 Heavenly Soldiers come over one by one, and the stick will become a very exaggerated state......" The group presented this level at the 2018 annual meeting. This part of the picture is shown at the end of the 13-minute video, and the state of the Heavenly Soldier now looks unnatural, and Feng Ji told me that they plan to redo this part. In the demonstration, the golden hoop stick in the Monkey King's hand can be made longer In 2019, the group grew to around 20 members, with the goal of "achieving a complete level". After discussion, it was decided that the level should at least "be of a quality that the player can experience". The name of this level is Heifeng Mountain. In "Journey to the West", Heifeng Mountain appeared in chapter 16 "Guanyin Temple's monk swindled the treasure, Heifeng Mountain's yaoguai stole the cassock". In the original novel, it is the first serious yaoguai / yaojing that Sun Wukong encountered on the way to get the Buddhist scriptures, and it is also the main content of the demonstration you see in the video. ^((\Heifeng Mountain:)* ***黑风山.****It literally means black winds mountain. That’s where Sun Wukong met the first decent yaiguai(different from those weak one)——the black bear*) ***(\Guanyin: 观音)****. The powerful bodhisattvas of Chinese Buddhism who helped Wukong many times on the way to the west. The bodhisattva has no gender, but in folklore, people have given Guanyin a female figure*) ^((\Yaiguai / yaijing: 妖怪/妖精.)* *Just like monster, kaiju, demon......*) 3. Although some preparations have been made, the Heifeng Mountain level is still harder to make than they imagined. "When you actually start it, it's really hard to make a level that has a narrative and allows the player to be emotionally engaged." Feng Ji told me, "There are many things in your heart, do you want the yaoguai to talk to you? What is this yaoguai doing when you are away? Why do you have to fight with him? I wonder if there should be some foreshadowing in the front?" All the "wants" are related to technology and industrial processes. Nowadays, originality is no longer the deciding factor for a high-investment commercial game, realization is more important. In reality, " realization" means several simultaneous workflows, each of which must be as efficient and quality as controllable as possible. If you want to do a short piece of engine-generated CG, the general process is as follows: first the literary planner writes the script, then the artist draws the 2D storyboard, and then builds a simple level model with a texture-free polygon model (because there are no textures, everything is white, which the developers call the level "white box"). Once you get the white box, you can make a dynamic storyboard inside. If you want to show a close-up of a character's face, you need to do it in motion capture, and they'll do it with an inertial motion capture device and then put it into the game to see how it looks. If there's something not right, you have to remove it and start again. If everything's OK, the optical motion capture can be submitted to produce the final product. During the game's development, there are countless production pipelines going on simultaneously. The larger the game and the more technologically advanced it is, the more uncontrollable it is. And if it gets out of control – whether quality or efficiency——it can end up being a disaster. They used Heifeng Mountain as a minimal workable model. Until everything was ensured, the development team was afraid to start a large-scale production. Feng Ji calculated the account for me very seriously, "For example, optical motion capture——a studio with 60 cameras, a team of dozens of people to serve you, the cost of a day is 200,000 to 300,000 RMB." If you say: 'I haven’t made up my mind today, so I won't do it yet.'——You still have to pay the money. ” Feng Ji showed me the playable version of the Heifeng Mountain level on the spot, and I also played it——the version is not very stable, and occasionally jumps out. He was a little nervous and keep reminding me that "the present feel is far from the best effect", "some skills have not been finalized", "the values need to be changed", "it is indeed not the final level, and there are still many details missing". Actually, I was surprised enough. There is no difference between the demo video and the actual playing. I heard that a streamer was quite excited after watching the demo of this game, and he sighed to his friends: "The 3A of China is coming!" The Heifeng Mountain boss battle in the demo But Feng Ji didn't want to mention the word "3A". On the one hand, he felt that this statement might attract some attacks, and on the other hand, he felt that the definition was completely imprecise ——"What do you mean by saying 3A? Of course we know what each A is, but the specific definition ...... Very vague.” "At least one A is that it costs a lot of money. I said, "Can you tell me about the cost of developing this game?" "You can think like this: if a player plays for one hour — not that they get stuck or die all the time, it's a relatively smooth gaming experience......," Feng Ji told me, "And the development cost per hour is 15 to 20 million RMB." 4. If you often go to Zhihu(a chinese app, just like Quora), you will see a series of questions related to "China" and "3A" every now and then, such as "Why doesn't China have 3A masterpieces?", or "When will China have 3A masterpieces?", and "Does China have to have 3A masterpieces?". These questions are full of good hopes, and some doubts about the fact that iron does not become steel - we already have the largest game company in the world, and we have such a profitable game industry—so why don't we have triple-A yet? Discussions about \"domestic games\" and \"triple-A\" always attract a lot of attention Sometimes, I think for a lot of people(including me), the "Triple A" is like a gold medal at the Olympics. There's a whole bunch of stuff behind it. Anyone who has been in the gaming industry for more than a year can easily say "what is between us and triple-A". But sometimes, you can't tell exactly what the problem is without doing it in person. If you watch the 13-minute promotional video carefully, you will realize that the monkey as the protagonist is silent most of the time—he doesn't speak, there are no close-ups of his face—all the characters have no close-ups of facial expressions. This inevitably makes people feel that the motive for the battle is not clear. Feng Ji said that this is actually a standard "technical problem". "There's an uncertain rumor that Naughty Dog has a 1:1 ratio of art and technical art. Feng Ji told me. You can think of technical art as "a badass person who understands both technology and art", which is not accurate, but not too wrong. Specifically, the job of Technical Art is to provide technical support to the art team and improve the quality and efficiency of art. To put it another way, if a job requires close collaboration between technology and art, then a technical art is needed. "One of the reasons why we wanted to find technical art was that we had to work on the story. Feng Ji said, "There are a lot of problems in motion capture, such as cohesion, environmental interaction, and alignment. Do you remember the battle with Ling Xuzi, that is, the wolf, at the end of the video?" ^((\Lingxuzi: 灵虚子.)* Black bear’s friend, also appeared in Heifeng Mountain. He wasn't a mighty yaiguai, in the original novel he was beaten to death by Wukong with just one hit. There's something strange about him, in the novel he is written as 凌虚子, but in the video it's written as****灵***虚子, the pronunciation of 凌 and 灵 is the same*) "Yes.” "Actually, the earliest version we designed was that the protagonist turned into a giant ape, and there would be a very exciting execution. The wolf pounced down from the roof, and the great ape held it up, grabbed its teeth with his hands, and pressed it to the ground, and then charge to the wolf. Feng Ji said, "Sounds good, doesn't it? Okay, as soon as the hand touches the teeth, it will be molded." We can't get the protagonist to stand in a stable position, so the teeth will come out of the fingers.” "Technical art is about solving these kinds of problems. "He can align the models and even determine what the material of each model is. In more advanced cases, the material of the tooth can even insert the flesh into the blood...... But we didn't do it well, we did it for two months, gave up, and changed the ending (that’s why another monkey appeared in the end). We delayed the design for several months this time, and in the end, we couldn't solve it." So, I didn't see the shot in the end. However, Feng Ji said that they did not want to give up, and sooner or later this execution would be made. Feng Ji told me a legend that in Naughty Dog, there is a separate button on each art's table. As soon as you press this button, a technical artist will come over and ask what the artist is having. "Is there a problem with the particle emitter, or does the fluid feel wrong? Or is there a problem interacting with the scene? I'll fix it on the spot.” Game Science knows the importance of technical art, but they don't have enough technical artists. Not only is there no game science, but there are not too many mature technical arts in China, and "they are all in big factories like Tencent and NetEase". But some of the problems were solved. In the promotional video, the monkey picked up a knife called "Red Tide". Feng Ji told me that it was not a pre-programmed animation. The monkey can walk over anywhere, clench the knife, pull it out of the ground and put it in the ear. The key here is to walk over and draw the knife. It took about two or three months for the development team to smooth out this movement, which most people are not aware of. Feng Ji stood up and demonstrated to me, "Have you played The Last of Us: Part 2? Have you ever noticed the movements of the characters in it? Like I'm sitting here, and the game prompts you to press a button, and you pick up an object——no matter where you're, whether you're facing something or sideways, the movement is very natural?" The rope in The Last of Us: Part 2 has a high degree of realism, whether it is bent in the player's hand or stretched and straightened, it is very natural I struggled to recall this inconspicuous detail in the game. Feng Ji continued. "We first thought it was to capture a few more movements, but then we found that the direction of the characters, especially the direction of the feet, is very subtle, if we only do frontal movements, what if the thing is on the side? Do you want to turn around? But there is no material for a smooth turn, and it is very strange to rely on procedural fusion——there are ways to achieve it without awkwardness, such as brute force cracking, I design 32 actions, just to take this knife, all directions are taken into account as much as possible. But in the game, you don't just have to hold a knife, you have to open a door, and you have to hold a hammer. If all actions are multiplied by 32, neither the production cost nor the amount of resources is acceptable.” Feng Ji continued, "Then we worked on methods, and watched the public speeches made by big manufacturers at GDC. Then we found out that Ubisoft had come up with a solution, which was "Motion Matching". The most powerful thing about this technology is that we only need to record a batch of basic motion animation data according to a set of rules, and then without any animator trimming, Motion Matching can automatically produce a complete set of smooth and natural character movements for you.” I asked, "Is this library open source?" "There are some opensource versions online, but they are very immature. We've made it production...... We pushed back the details of Ubisoft's various plans, and in some places Ubisoft didn't disclose the specific implementation method, we also managed to make it, such as what specifications to design the whole set of movements, how to realize some strange walking animations......" Feng Ji said, "But if you compare yourself with Assassin's Creed: Odyssey, or even bolder, with God of War or The Last of Us, you will find that you are just not as good as it." Their library of basic actions and corresponding math algorithms are a black box for you. But it's also their moat.” I asked him, "If you make all of this, it will be your moat?" "Of course——But they have a lot of iterations of generations, and there is no way to do this quickly." 5. They still have to keep making choices. For example, the style of play, is it going to be a Monster Hunter style game, or a God of War style game, or a Soul game? They found that each style corresponds to a different emphasis and detail. If you study God of War, the focus of development will be on the performance and execution, and if you study Monster Hunter, you will first have to solve the problem of large-scale enemy movements. If you're going to make a Soul game, you're dealing with character growth and duel-style combat——there are challenges in every direction, and the most important thing the development team wants to know is what the overall feel of the game will be for the player. They want to be sure about "how would the player describe our game?" This bothered them for a while, and then Feng Ji figured it out, "If we go to benchmark a very specific product...... You will naturally turn into a second-rate game. Even if you can pay tribute well, it will naturally make players feel like a second-rate game.” They began to consciously distance themselves from the best of the best. "I'll admit that they have probably the best solution for the current action game. Feng Ji said to me, "But we have to keep our distance from these games." They don't want players to directly associated Blackmyth Wukong with a certain design of a specific game. As a result, they abandoned their weapon parry and used the "Copperhead Iron Arm / Unbreakable body", they prowl by turning into a cicada. ^((\Copperhead Iron Arm:)* 铜头铁臂. *Now there is no accurate translation of this spell, in short, it means that the body is as hard as metal, almost unharmed. In the novel, the Monkey King's body has always been indestructible, but it needs to be used as an active skill here in game.*) ^((\Cicada: 蝉.)* *Wukong always turned himself into a cicada/a fly/a bat......to sneak into yaigauis’ caves*) In the demo, the Monkey King, who transforms into a golden cicada, will not be discovered by ordinary miscellaneous soldiers Level design is another issue, Feng Ji used to be very obsessed with the box-style design of "souls" games, the so-called box-style design, almost specifically refers to the sandbox-like levels achieved by Japanese games with highly accurate design. But by the end of 2019, as development progressed, the development team realized that Blackmyth Wukong wasn't a good fit for box-style level design. After discussion, the development team finally decided that if they wanted to express the grand epic sense of "Journey to the West", it was more appropriate to use multiple levels + teleportation to represent their big mythological world, so that each map could have more design ideas. But Feng Ji also retains the right to "make a certain sense of box court on a single map". "Of course, I will respect the requirements of art for realism. Many scenes in "Dark Souls" are churches, and you can design a lot of loops, up and down, but you can't force a lot of steps or elevators in the forest, ......right? So we will do it specifically, Heifeng Mountain is a little flat, and Leiyin Temple can be deeper...... But I still want to keep a certain amount of openness, so that players can still explore the map.” ^((\Leiyin Temple: 雷音寺.)* ^(\It literally means a temple with sound of thunder. It’s the destination of journey to the west in novel. And there are two Leiyin Temple, one is real, and another is created by the Yellow Eyebrow King(****黄眉大王**** to deceive Sun Wukong and his partners. The author called it "Little Leiyin" in his novel, Game Science translated it as "New west" in the TGA trailer. The Yellow Eyebrow King is a person who ran away from the Lei Yin Temple, his story is in chapter 65)*)*) Feng Ji was keen to tell me about the worldview and overall style of the game, but I decided not to reveal too much here. I can't make much of a judgment until I see the final presentation. This game is not a replica of "Journey to the West", and they don't want to continue the sharp style of "Asura" that subverts everything and challenges everything. They sometimes don't want to talk about Asura, and they seem to be a little worried about what players will say when they think of that game. But they still wanted to tie this game to their first game, Asura. For example, in the 13-minute video, the subtitle at the end is "After Baigu, go back to the west". (\Baigu: 白骨****. It literally means white bone, and Baigu yaiguai appears in chapter 27 of the novel. They adapted this part totally when creating Asura*. "Do you know why we say this?" Feng Ji said to me, " Asura players have a meme, called 'After Baigu, there is no Journey to the West'. We planned 5 chapters at that time, and the third chapter is called 'Goodbye Madame', and Madame refers to Mrs. Baigu——we did 3 chapter of the plot in total, and there was a plot animation and dubbing, which was very good, but it came to an abrupt end in the third chapter. The task descriptions later were all textual later. That's why players say that.” The CG of \"Goodbye Madame\" in \"Asura\" left a deep impression on players. On August 20, when the video was released, Yang Qi post a microblog on Weibo: "(This theme) is a burden for us for more than ten years. Many colleagues don't say it, but everyone knows that this knot is unavoidable. It's an honor to show you the progress of the development today, and we will do our best in the future, hope we will never disappoint you again.” I asked Feng Ji on WeChat: "Can you help me ask Yang Qi, why use the word 'again'?" Feng Ji replied to me: "He probably thinks that "Asure" has regrets. Then he added, "I have that too, but I don't have any resentment."” I asked, "Resentment? To whom?" Feng Ji said: "To me, I was not so brave at that time.” 6. I showed some of the articles I had written to a friend. I said to my friend, "I don't want people to feel like the whole development is very tough——like reportage in the '80s.” "It's okay. My friend said, "I still feel a little bitter, not very serious." "Then I'll change it. I said, "I'm afraid that some people will think they are bitter, but in fact they are really not bitter, and they are so happy." When chatting with Feng Ji and Yang Qi, I asked them, what are you most worried about after the video is released? Feng Ji said that his biggest concern is that the video does not get the response they expected and goes unnoticed. Yang Qi is worried that after the video is released, many manufacturers will poach people. But as a bystander, what worries me most is the suspicion and attack of public opinion on them——suspecting that this is CG, animation, and deception, accusing them of playing with feelings, swindling, and sadfishing. As of the morning of August 21, Yang Qi's trailer has been reposted nearly 100,000 times on Weibo, almost all of which are praises and praises It's not to blame the players. Every suspicion corresponds to at least a few cases that have occurred. Players deceived by fake propaganda——getting angry, and then cynical, believing that giving trust and enthusiasm is a dangerous thing to do. At the same time, "feelings" have become a derogatory term because they have been abused. There seems to be some kind of paradigm, when we say that some people decide to pursue their ideals, we have to express the choices and sacrifices they make, including some noble and sad keywords, some typical moments, like a lonely back walking towards the sunset. But Feng Ji and Yang Qi did not show bitterness, unwillingness, entanglement and sacrifice. Feng Ji's eyebrows fluttered when he talked about this game. He would start with a certain point, keep spreading, keep associating like Wikipedia, and talk farther and farther. And that's why I need to ask myself again, "does this article describe the joy they showed?" You know, when people are doing what they love, everything they see is so nice. At the end of that conversation, I don't know why, maybe because of a certain sentence, or some kind of opportunity, our conversation went in a strange direction. "Yang Qi used to tell me that if we walk on our knees now, we can walk to a mountain of gold and silver——that is, we can make a lot of money. If you can succeed by walking on your knees, I will kneel with you right away. You don't have to convince me, I really want to make money. Now the question is, what path can you tell me that can definitely make money in this kneeling way? "I really can't answer him. Feng Ji said to me, "Many people point to a product today and ask me, is it possible to succeed by just learning it and strengthening our strengths? But you also know that many people have better execution and resources than you, so how can you compare with them? So in the end, you still rely on your own intuition——you have to impress yourself first, only when your own intuition is strong, you are more likely to impress users." If you're not sensitive to something——let's put aside anything like Ego——you're not sensitive, and your iteration speed will lose to those who have more passion, then how can you succeed?" But even then, they may still not succeed in the end. Game development is a long-term ongoing project, especially for a game of this magnitude. There are still a lot of problems with the current promotional video, such as the fact that they have been developing it silently for two years, and the number of developers has changed from 7 to 30 now. In the future, they will spend at least two years to develop, there is still a lot of work to be done, a lot of people to join the team, and a lot more to happen. After the video was released, Feng Ji began to feel a little anxious. He told me on WeChat that he was a little worried about being held too high. "It's just that I don't really feel safe yet...... I'm just this kind of person——hard to be happy until things really happens." I told him he would get used to it—it wasn't just a pure blessing. Actually, it seems to me that maybe he doesn't realize it now, but it's already happened. All these praise and exclamation is exactly part of the matter and is the reward that the team deserves. I'm still willing to believe that. When you decide to do something you really like, good things happens. 7. A few days before the video was released, Game Science continued to release the teaser poster on its official Weibo. One per day, each poster is accompanied by a few sentences or a short poem. On August 19, the day before the trailer was released, they capitated the poster with the words:" I was so much older then,I'm younger than that, now." The \"poster\" is actually a video, accompanied by the sound of a bonfire burning and beeping, and the person in front of the camera is shaking a fan and staring at the campfire, you can find more images on their website: https://www.heishenhua.com/ This quote comes from the song "My Back Pages" by American folk superstar Bob Dylan. In this song, Bob Dylan cricitized and ridiculed his past without hesitation (Incredibly, he was only 23 years old at that time). The song has a total of 6 bars, and each bar is preceded by an introspection on his past, followed by this sentence. The last two bars go like this—— In a soldier's stance, I aimed my hand At the mongrel dogs who teach Fearing not that I'd become my enemy In the instant that I preach My existence led by confusion boats Mutiny from stern to bow Ahh, but I was so much older then I'm younger than that now Yes, my guard stood hard when abstract threats Too noble to neglect Deceived me into thinking I had something to protect Good and bad, I define these terms Quite clear, no doubt somehow Ahh, but I was so much older then I'm younger than that now Epilogue. |
2024.04.04 21:07 mikansana FERIA DE LIBROS - MUCHOS EN INGLES Y UN PAR EN ESPAÑOL
2024.04.03 22:42 DustOfTheEndless Books seen in HBO Girls
2024.03.28 18:40 CapOk2664 The loner reads his books...
2024.03.15 10:23 sundayquiz Friday 20 Question Quiz - Authors and General Knowledge
2024.03.15 10:22 sundayquiz Friday 20 Question Quiz - Authors and General Knowledge
2024.03.09 08:04 jtjdp Structure-Activity Relationships of the Benzimidazole Opioids: Nitazenes and Piperidinylbenzimidazolones (Cychlorphine, Brorphine, Bezitramide Derivs) [Vol 1]
Structure-Activity Relationships of the Benzimidazole Opioids: Nitazenes and Piperidinylbenzimidazolones (Cychlorphine, Brorphine, Bezitramide Derivs) - [Vol 1: Nitazenes]---------------------------------------------By: Oxycosmopolitan X.com/DuchessVonD Patreon.com/Oxycosmopolitan u/jtjdp AskChemistry ----------------------------------------- The world of chemistry pulsates with the creative energy of its practitioners. It is a realm where imagination takes flight, conjuring new molecules with the potential to revolutionize how we treat disease, understand life, or even alter the course of human history. However, the journey from conception to tangible reality is fraught with difficulty. Unexpected hurdles lie in wait. Transforming a dream molecule into a practical therapeutic is far from guaranteed. Failure awaits most ventures. These failures are studied, formulas improved. Failure breeds success. Success is founded in failure. “If you aren’t frustrated, you aren’t doing hard science.” Repeatedly beating one’s head against the wall is a hallmark of great scientists. Those with unmarred foreheads, like my own, are usually just mediocre. I’m too vain to be anything but mediocre. The modern chemist operates within a complex landscape. Gone are the days of unfettered exploration, where ideas could blossom unhindered. Instead, regulations and obligations hold sway, demanding careful consideration and responsible practice. Yet, amidst these constraints, a multitude of approaches exist to guide the design of these coveted molecules. One particularly reliable approach involves drawing inspiration from the success of existing structures. By studying molecules with established efficacy, the chemist embarks on a quest to improve upon their therapeutic potential through targeted molecular modifications. This journey of optimization, fueled by both creative vision and scientific rigor, lies at the heart of this fascinating field. Fifteen years ago, at the beginning of my chemical career, an era when I spent more time hitting on boys than I did the books, I was inspired by the resonant beauty of a different type of beau. It was neither furbaby, frat boy, or the cute nerd from the library: it was benzimidazole – my bundle of aromatic joy! More specifically, I was attracted to the NOP/ORL1 and μ-opioidergic potential [http://dx.doi.org/10.1021/bk-2013-1131.ch008] of the relatively niche 2-benzimidazolone derivatives that were first pioneered by Paul Janssen in the early 1960s. The marriage of 2-benzimidazolone resonance with the C4 position of piperidine gave birth to a scaffold with diverse pharmacology: the 4-(2-keto-1-benzimidazolyl)piperidines. Also referred to as piperidinylbenzimidazolones or the more “Charmed” nomenclature, 4-benzimidazolonepiperidines. The 4-(2-oxo-benzimidazolyl)piperidine scaffold was first utilized by Janssen to grow his portfolio of antipsychotic-neuroleptic agents. Janssen coupled the piperidinylbenzimidazolone moiety with a halogenated N-butyrophenone to form the dopamine antagonists benperidol, droperidol and domperidone. Concurrent with the discovery of neuroleptics of the benzimidazolone series were opioidergic members based on the same scaffold. There is significant overlap in Janssen’s diverse portfolio of dopamine antagonists with those of his opioid portfolio. Most of Janssen’s classical neuroleptic scaffolds are readily converted to highly selective μ-opioid receptor agonists by replacing the butyrophenone moiety with an opioactive moiety. The most active of these include: p-Halogenated benzyl (brorphine; clorphine) N-cyanoethyl + p-halo benzyl (cychlorphine, cybrorphine): analgesic activity up to 230 x morphine p-Methyl benzyl (warorphan): 130 x morphine Methadyl (R4847; etodesitramide): up to 200 x morphine Diphenylbutyronitrile (bezitramide, desitramide): 10-15 x morphine Diphenylpropyl (R5460): 60 x morphine Additional opioid-activating moieties are found in the following diagram (not a comprehensive list). [https://i.imgur.com/Lb3lHYE.jpg] [REFS: Janssen - Drugs Affecting the Central Nervous System, Vol 2 (1968) - A Burger, ed.; https://doi.org/10.1016/0014-2999(83)90331-x; https://doi.org/10.1016/0014-2999(77)90025-5; https://doi.org/10.1208/aapsj070234; https://doi.org/10.1016/s0960-894x(03)00665-6; https://doi.org/10.1248/cpb.49.1314] Janssen’s 2-benzimidazolone odyssey culminated in the clinical development of the long-acting analgesic bezitramide (100 x pethidine). Despite its potential, bezitramide was poorly soluble with low bioavailability and did not see widespread adoption. He would continue to utilize the scaffold in his psychiatric portfolio, but bezitramide was the last commercial venture in its class. Other members of the class, especially those derived from N-despropionyl bezitramide, are highly active opioid analgesics with potencies ranging from 10-230 x morphine. Research into the scaffold was revived by Kennedy et al. as a platform for developing biased μ-opioid receptor (μOR) agonists. [https://doi.org/10.1021/acs.jmedchem.8b01136] Several of the ligands from the 2018 study have appeared as designer drugs, including brorphine and the 5,6-dichloro congener SR-17018. The piperidinylbenzimidazolone series was initially developed alongside fentanyl – the most successful of Janssen’s opioid discoveries. The 2-benzimidazolones can be imagined as closed-ring analogs of the propionanilide substructure within the fentanyl molecule (see red arrow in the diagram below). The evolution of the piperidinylbenzimidazolones from their humble methadylic and fentanylic roots and their latter-day ethylenediamine derivatives is outlined in the following diagram: https://preview.redd.it/ptocngnmz8nc1.jpg?width=2402&format=pjpg&auto=webp&s=fdc327a99ef9c5a74a1aab830a293197e0eb24fd [https://i.imgur.com/4Qy3RRl.jpg] Members of the piperidinylbenzimidazolones, such as cychlorphine and its congeners, will be more fully explored in the second volume of this two-part series. The first volume is dedicated to members of the nitazene series: 2-benzylbenzimidazoles. —--------------------------------------------------------------------------------------------------------------------- Karma is a Benzimidazole, who doesn't play with balls (Deandra’s Version) Benzimidazole stands out as a prominent player in the realm of heterocyclic pharmacophores, earning the reputation as a privileged structure due to its frequent presence in bioactive molecules [https://doi.org/10.1016%2Fj.jscs.2016.08.001]. This unique aromatic scaffold emerges from the fusion of two aromatic rings: benzene and imidazole. As an amphoteric moiety, benzimidazole embodies characteristics of both acids and bases. Additionally, benzimidazoles have the ability to form salts, further broadening their potential. https://preview.redd.it/x3mldahxz8nc1.jpg?width=955&format=pjpg&auto=webp&s=6edae983dd7da7d0ca86b503866d355e27a9b839 [https://i.imgur.com/coC3yjd.jpg] This unique structure imbues its derivatives with interesting properties and diverse chemical reactivity. [https://doi.org/10.1016%2Fj.apsb.2022.09.010] The benzimidazole structure offers a unique combination of aromatic character and planarity, contributing significantly to its properties and reactivity. [https://doi.org/10.3390%2Fmolecules28145490] Both the benzene and imidazole rings exhibit aromaticity, granting them stability due to delocalization of π-electrons throughout the conjugated system. [https://doi.org/10.1039/B40509] This aromaticity also translates to a planar structure for the molecule, enabling crucial interactions with biological targets. This planarity facilitates π-π stacking, where the π-electron clouds of the benzimidazole ring overlap favorably with aromatic moieties present in the active sites of target receptors. These interactions, driven by transient electrostatic forces, contribute to the stabilization of the complex and enhance the binding affinity of the benzimidazole moiety to its target. [https://doi.org/10.1107%2FS1600536809027391] While the aromatic framework confers stability, the presence of nitrogen atoms in the imidazole ring introduces a degree of polarity. This polarity arises from the uneven distribution of electrons, rendering the molecule slightly basic. These nitrogen atoms also contribute to the amphoteric nature of benzimidazole. Depending on the reaction environment, the molecule can act as an acid by donating a proton (H+) from the NH group, or as a base by accepting a proton from an acidic species. The unique electronic distribution within the benzimidazole structure influences the reactivity profile of this versatile substrate. [http://dx.doi.org/10.2174/1570179420666221010091157] The positions 4, 5, 6, and 7 (relative to the imidazole ring) are electron-rich. This electron-rich character makes these positions susceptible to attack by electrophilic reagents, leading to reactions like nitration, halogenation, and sulfonation. Conversely, the 2-position exhibits electron deficiency due to the electron-withdrawing nature of the adjacent aromatic ring. This electron deficiency makes the 2-position a favorable target for nucleophiles, facilitating nucleophilic substitution reactions. This specific reactivity is particularly relevant in the context of 2-benzylbenzimidazoles, where the 2-position serves as the anchor point for the para-substituted benzyl moiety present in compounds like etonitazene. Benzimidazole generally displays resistance towards both oxidation and reduction reactions. However, under harsh conditions, the benzene ring can be susceptible to oxidation. Conversely, the aromatic character of the molecule contributes to its resistance towards reduction. The acid/base properties of benzimidazoles are due to the stabilization of the charged ion by the resonance effect. The substitution pattern of benzimidazole derivs (such as nitazenes) influences the reactivity of different regions of the molecule and alters its physicochemical properties. [https://doi.org/10.2174/1389557519666191122125453] The two nitrogens of benzimidazole have different properties and acidities, increasing the ring system’s electronic diversity and utility as a synthetic scaffold. The pyridine-like nitrogen, aza (–N=), is an electron donor (labeled N1 in diagram), while the pyrrole-like nitrogen, an amine (–NH–), acts as an electron acceptor (labeled N2). Benzimidzole’s nitrogens are somewhat less basic than the corresponding pair in plain vanilla imidazole. This makes benzimidazoles more soluble in polar solvents and less soluble in organics. Unsubstituted benzimidazole, for example, is soluble in hot water but poorly soluble in ether and insoluble in benzene. https://preview.redd.it/gcil3y0zz8nc1.jpg?width=878&format=pjpg&auto=webp&s=16f814d564613672a9e31534a74f991c11b8dffc [https://i.imgur.com/9DjyBfU.jpg] In unsubstituted benzimidazole, a rapid proton exchange occurs between the nitrogen atoms (–NH– and =N– see above figure). This phenomenon, known as tautomerism, gives rise to two equivalent forms of the molecule that exist in an equilibrium. The transformation can occur either between individual benzimidazole molecules or with the help of protic solvents like water. This exchange makes substituents at the C5 and C6 positions chemically identical. However, the magic fades once you introduce a substituent to the N1 nitrogen (N-substituted benzimidazoles). This disrupts the dance, locking the molecule into two distinct and isolatable forms, like twins that can finally be told apart. [https://doi.org/10.1016/0169-4758(90)90226-t90226-t)] As the nitazene species are highly substituted benzimidazoles, the position of the substituent along the C5-C6 benzene axis is just as critical to bioactivity as the nature of the substituent itself. The opioidergic activity of the C5-C6 regioisomers of the nitro nitazenes varies substantially. In the case of the series prototype etonitazene (5-nitro), shifting the nitro group from C5 to C6 results in an activity loss of nearly 100-fold. [https://doi.org/10.1039/J39660001511] [ABOVE: Anatomy of 2-benzylbenzimidazole prototype, etonitazene, featuring optimal substituents: 5-nitro (electron withdrawing group = EWG), 2-benzyl (p-ethoxy optimal), ethylenediamine side chain (diethylamino optimal)] [https://i.imgur.com/dF1ZnXz.jpeg] As with chemical reactivity, the solubility of substituted benzimidazoles varies. The aliphatic side chain (blue in diagram) and 2-benzyl substituent (green) of etonitazene contribute to a very high lipid solubility. The ionization constant of the diethylaminoethyl side chain (branching from the pyrrole nitrogen) contributes to greater acidic character compared to the unsubstituted benzimidazole. Combined with the increased lipophilicity, this translates to lower aqueous solubility and increased solubility in organic solvents. The ionization constants (pKa) for the nitrogens in etonitazene are as follows: pyrrole-type (N2) is 2.86 and that of the aminoethyl side-chain (N3) is 6.36. [https://doi.org/10.1111/j.2042-7158.1966.tb07782.x] https://preview.redd.it/9ky1ghx309nc1.jpg?width=3551&format=pjpg&auto=webp&s=5cb67cf4a5a1a5bb6a0a0bb928c8a8eca9d3eb66 [https://i.imgur.com/39pQFP9.jpeg] [ABOVE: The anatomy of piperidinylbenzimidazolone opioid analgesics. The 2-benzimidazolone core of series prototype (brorphine) attaches to C4 of the piperidine ring, forming the crucial 4-piperidinylbenzimidazolone core] ------------------------------------------------ History The path to fully synthetic opioids began with the elucidation of the chemical structure of morphine. [Mem. Proc. Manchester Lit. Philos. Soc. 1925, 69(10), 79] Before the vast array of analytical tools we take for granted today, pinpointing the exact structure of complex natural products like morphine was a major challenge. Gulland-Robinson (1925) and Schopf (1927) independently proposed the structure we now accept, but only the 1952 total synthesis of morphine by Gates and Tschudi [https://doi.org/10.1021/ja01124a538] confirmed it definitively. Just two years later, Elad and Ginsburg reported an intermediate convertible to morphine, solidifying the picture With a rudimentary framework of morphine’s structure, researchers sought an improved drug with better oral activity and less addiction potential. In 1929, a US National Research Council program embarked on this mission, systematically modifying the morphine molecule and establishing the structure-activity relationships (SAR) of the 4,5-epoxymorphinan class. This small group included Nathan B. Eddy and EL May, who would later become leaders in the field of addiction research. The aim of their 11-year odyssey was to discover improved analgesics through elucidation of simpler fragments of the morphine molecule. While contributing greatly to the structure-activity relationships of morphine derivatives, their ultimate goal of discovering less addictive narcotics was elusive. Two morphine analogs resulting from the project, desomorphine and metopon, demonstrated reduced dependence potential. Based on the recent emergence of Krokodil (homebake desomorphine) on the Russian exotic reptile market, it seems doubtful that the reduced addiction liability of desomorphine observed in rodents translates to humans. [NB Eddy, “The National Research Council Involvement in the Opiate Problem, 1928-1971” (1973)] Before the spindly 11-year odyssey of their American colleagues concluded, a series of discoveries at German pharma firm Hoechst AG would rock the field of analgesics like a blitzkrieg bukkake. Eisleb introduced the first fully synthetic opioid when he synthesized pethidine (meperidine) in 1937 [https://doi.org/10.1055/s-0028-1120563], followed by Schaumann’s elucidation of its morphine-like mechanism of action a year later. Later that same year (1938), Hoechst’s chief of R&D, Max Bockmuhl, and his eventual successor, Gustav Ehrhart, discovered morphine-like analgesia in a series of straight-chain diphenylpropylamine derivatives [https://doi.org/10.1002/jlac.19495610107]. The prototypes of this class, methadone and its α-methyl isomer isomethadone, would go on to inspire many of the first synthetic opioids introduced to the clinic (dipipanone, phenadoxone, dextromoramide, normethadone, LAAM, dextropropoxyphene). Aspects of this 3,3-diphenylpropylamine scaffold, such as the ethylamino side chain and the methadyl moiety, would be incorporated into the design of 2-benzylbenzimidazole and 2-benzimidazolone opioids. To learn more about the chemistry and pharmacology of methadone, isomethadone and other 3,3-diphenylpropylamine opioids, see my review here: [https://www.reddit.com/usejtjdp/comments/11jbjmy] ------------------------------------------------------------ Percocet in Peacetime The immediate postwar period ushered in an explosion of research dedicated to the elusive "Holy Grail" of analgesics: a pain reliever devoid of the dark side. These ideal analgesics would have fewer side effects, such as respiratory depression, constipation, sedation and dependence liability. In this “morphine python quest for the holy grail,” several key discoveries stand out. https://preview.redd.it/hya6t67b09nc1.jpg?width=5981&format=pjpg&auto=webp&s=6e8261d7228e5914df9ead6e0f0524fbe1baf40a [https://i.imgur.com/0hHsSz6.jpeg] The structural complexity of morphine presents a significant challenge to the natural product chemist. The cis-(1,3-diaxial) geometry of the iminoethano bridge (the top half of the piperidine; ring D) frustrated early attempts at total synthesis of this molecule and its relatives. Much of the early work, in fact, focused on construction of a “model hydrophenanthrene” scaffold containing the important quaternary center (corresponding to C13 in the morphinan skeleton). A cyclodehydration reaction developed in the course of this research provided a necessary tool for much of the subsequent work. The speculative scheme for the biological origins of morphine, as proposed by Robinson and Schopf in the mid-late 1920s, is likely to have inspired the successful synthetic scheme for prep’n of simpler versions of the morphine nucleus. These proposals detailed the cyclization of a benzylisoquinoline into the desired morphinan nucleus. Another 40 years would pass before these postulates were confirmed by studies involving the (in vivo) conversion of radiolabeled norlaudanosoline into morphine (in plant tissue). Using the postulates of Robinson-Schopf as templates, the young chemist Rudolph Grewe prepared a substituted 1-benzyloctahydroisoquinoline (known in industry as “octabase”). Grewe spent the better part of a decade (1942-49) tinkering with different cyclization conditions in order to convert octabase into the cis-(1,3-diaxial)-fused morphinan structure observed in morphine. This ring closure was accomplished via a carbonium ion mechanism and effected by heating octabase in concentrated phosphoric acid, yielding the morphinan nucleus – see (14R)-levorphanol in the above figure. Levorphanol was a useful addition to the clinicians toolkit. It was the first analgesic to pair supra-morphine potency with substantially reductions in dependence liability. Levorphanol has been used for decades as a tolerance-attenuation agent in high-dose morphine patients (attributed to levorphanol’s `incomplete cross-tolerance’ with other opioid analgesics). For a detailed review of Grewe Cyclization, see my reddit post: [https://www.reddit.com/AskChemistry/comments/p4z5sx/] While the holy grail of opioid analgesics devoid of side-effects remained elusive, the outlook among opioid researchers was one of optimism. The year 1952 saw the formal synthesis of morphine by Gates & Tschudi [https://doi.org/10.1021/ja01124a538]. Their achievement holds a distinguished position in the annals of organic chemistry, not just for being the first, but also for its impact on the field of natural product chemistry. This synthesis marked a pivotal moment in the field of total synthesis by showcasing the potential of the Diels-Alder reaction for the construction of complex structures. [https://doi.org/10.1021/ja01630a108] This powerful reaction, forming a cyclic structure from two simpler molecules, became a cornerstone in organic synthesis, employed in numerous subsequent syntheses of natural products and pharmaceuticals. A decade after Gates’ total synthesis, KW Bentley utilized [4+2] cycloaddition [https://doi.org/10.1016/j.ejmech.2020.112145] to systematically explore a series of Diels-Alder adducts of thebaine, i.e. 6,14-endoethenooripavines (“orvinols”). His discoveries in this class were so numerous, that they have been given their own class: the aptly named “Bentley Compounds.” [doi.org/10.1111/j.2042-7158.1964.tb07475.x] Bentley’s research resulted in several currently marketed drugs, including buprenorphine and dihydroetorphine (used primarily for opioid maintenance), and etorphine/diprenorphine (used in veterinary medicine). [https://doi.org/10.1016/B978-0-08-010659-5.50011-1] The Bentley series is noteworthy for high analgesic potency and their ability to substitute for opioid dependency with minimal side effects. Dihydroetorphine, upwards of 10,000 fold more potent than morphine, is used extensively in China as a maintenance medication and has an exemplary safety record. [https://doi.org/10.1111%2Fj.1527-3458.2002.tb00236.x] Total synthesis provided researchers access to the synthetic dextro-antipodes of morphine and the inactive enantiomers of related 4,5-epoxymorphinans. [https://doi.org/10.1039/JR9540003052] Access to the unnatural (+)-morphine enantiomer helped researchers elucidate the complex stereochemistry of the 4,5-epoxymorphinan nucleus, which remains the most popular class of opioids in modern pharmacopeia. [https://doi.org/10.1021/acschemneuro.0c00262] For a review of the history and chemistry of the morphinan superfamily, see my reddit post: [https://www.reddit.com/AskChemistry/comments/opnszl] In 1954, AH Beckett and AF Casy published one of the most influential theories of the early opioid era: the Beckett-Casy Postulate [https://doi.org/10.1111/j.2042-7158.1954.tb11033.x]. The researchers analyzed the structure-activity relationships of morphine-like agents and proposed a set of structural, steric, and electronic requirements that were shared among the opioid ligands of the era. This became a proto “opioid pharmacophore,” that is, a rough template of the structural requirements for high activity at the proposed “Morphine Receptor.” The existence of a common site of action among morphine-like agents was supported by what was known at the time: stereotypical “narcotic cues” demonstrated by animals upon administration of both semi-synthetic and fully synthetic analgesics (Straub tail, anti-mydriasis, respiratory depression, antidiarrheal, cough suppression). While the quantitative potency varies widely (i.e. fentanyl vs codeine), the qualitative effects of analgesia and the side-effects following drug administration are consistent across natural and synthetic morphine-like agents. This formed the basis of the theory of a common site of action. 1954 Beckett-Casy Postulate - early Model of the mu Opioid Receptor [https://i.imgur.com/epFABkr.jpg] While the proposed pharmacophore held a more humble understanding than modern receptor theories, the Beckett-Casy Postulate (also known as the “Morphine Rule”) was impressive given that the “analog models” of the era were still crafted by hand and often molded out of papier mache. The hypothesis provided a convenient rule of thumb used by drug designers to quickly determine the likelihood of a compound having morphine-like activity. Compounds conforming to the rule were explored further, while structures that didn’t obey were made to sleep in the doghouse until they learned proper manners. Their theory combined the earlier SARs of morphine derivatives elucidated by NB Eddy during the 1930s with those of the newfangled fully synthetic analgesics, such as methadone and pethidine. Core features essential for strong opioidergic activity (Beckett-Casy Postulate) [https://i.imgur.com/hEjeDlg.jpg] The following core structural features were determined to be essential for strong analgesic activity:
The figure below shows the structural features common to morphine (pentacyclic 4,5-epoxymorphinan) and prototypes from three important synthetic opioid classes: levorphanol (tetracyclic morphinan), pethidine (4-phenylpiperidine) and methadone (3,3-diphenylpropylamine). https://preview.redd.it/i54h2chp09nc1.jpg?width=3487&format=pjpg&auto=webp&s=9f0d22653daa1b44da5319307d22d973569d6d2b [https://i.imgur.com/hE0eAp4.jpeg] While the morphine rule offers a valuable framework for understanding opioid activity, there are exceptions and limitations. One of the first challenges to the universality of the Morphine Rule came from a key structural feature of the nitazenes: the diamine side chain. —--------------------------------------------------- Enter Nitazene… In 1957, researchers at CIBA (Hoffmann, Hunger, Kebrle, Rossi) found that a minimally substituted 2-benzylbenzimidazole, 1-(β-diethylaminoethyl)-2-benzylbenzimidazole, induced a Straub tail response in mice. The Straub tail reaction is a highly sensitive narcotic cue that is indicative of morphine-like mechanism of action. Despite lacking the potency-enhancing accouterments of etonitazene (5-nitro and p-ethoxybenzyl substituents), this homely-looking structure demonstrated analgesic activity on par with codeine (one-tenth morphine). This finding was of sufficient interest to spur elucidation of the structure-activity relationships of this novel series. And so the ugly duckling benzimidazole became the proteus of a dynasty. https://preview.redd.it/7734j43s09nc1.jpg?width=2116&format=pjpg&auto=webp&s=8972f550794ffeb2662aa14d9347f20d2ff81a49 [https://i.imgur.com/RoTsrOO.jpg] At the time of the discovery of the nitazenes, the diamine system was an uncommon structure within the opioids. Most clinical opioids are monoamines. One nitrogen to rule them all. In the morphinan class, nitrogen functionalization outside of the 17-amine position (the iminoethane bridge) is rare. The addition of multiple nitrogens into the morphinan nucleus has a deleterious effect on activity. At the same time as the discovery of the 2-benzylbenzimidazoles, researchers at American Cyanamid discovered a series of morphine-like diamine analgesics based on the N-(tert-aminoalkyl)-propionanilide scaffold, including phenampromide and diampromide (Pat # US2944081A; https://doi.org/10.1021/jo01061a049]. As with nitazenes, the design of the ampromide class was influenced by lessons learned from the 3,3-diphenylpropylamine series [https://doi.org/10.1002/jps.2600511131]. https://preview.redd.it/nwemwk5u09nc1.jpg?width=4375&format=pjpg&auto=webp&s=48c1e75b753a7a7d5956be815d9456a51a032200 [https://i.imgur.com/WEhPd6w.jpg] The nitazenes were the first opioid analgesics to successfully incorporate the diamine into a highly active μ opioid pharmacophore. This dynamic amine system contributes to the high activity observed in the series. It consists of two basic moieties: the pyrrole-like nitrogen incorporated into the aromatic benzimidazole system and a tertiary amine in the side chain. This diamine function endows them with the ability to exhibit both acidic and basic character depending on the surrounding environment. This is known as amphoterism. The benzimidazole ring system experiences a reduction in apparent basicity due to the electron-withdrawing nitro group substitution. In etonitazene, the benzimidazole amine has a pKa of 2.86. This translates to an estimated 22% of the molecule being protonated at physiological pH (7.4). Conversely, the side chain amine boasts a higher pKa of approximately 6.36. Furthermore, the nitazenes are highly lipid soluble, indicating rapid absorption and a distribution that favors the lipid rich CNS. This is exemplified by their lipophilic Log P range of approx 4.1 to 5.1, highlighting a pronounced preference for nonpolar environments. The nitazenes have greater lipid solubility than fentanyl, which possesses a Log P of 4.05. A comprehensive understanding of the acid-base properties and lipophilicity of these molecules is crucial for elucidating their pharmacological behavior. Their dual acidic and basic character allows for interactions in diverse environments, while their high lipophilicity facilitates penetration through biological membranes, contributing to their potent CNS-mediated effect. NITAZENE CHEMISTRY Of the variety of routes to benzimidazole derivatives, the most popular are modifications of the classical acid-catalyzed cyclocondensation of 1,2-phenylenediamine.derivs (first devised in the late 19th century). The Ladenburg-Phillips reaction is a versatile and efficient method for synthesizing benzimidazoles. It involves the condensation of an o-phenylenediamine with a carboxylic acid, ester, acid chloride, or anhydride, followed by cyclization. This reaction was first reported in the 1870s and has since been used to prepare a wide variety of benzimidazoles with different substitution patterns. Carbonyl equivalents such as carbonitriles, imino-ethers, or amidines can also be used. The reaction is catalyzed by HCl, polyphosphoric acid or boric acid. The Weidenhagen reaction can be adapted using Cu(II)-mediated oxidative cyclocondensation to prepare benzimidazoles. Synthesis of Nitazenes: [For a full review of nitazene synthetic methodology, see the full version of this article at Patreon.com/Oxycosmopolitan] -------------------END OF PART I----------------- To read the full version of this article, visit Patreon.com/Oxycosmopolitan |
2024.03.08 00:23 cerberus00 Madame Bovary has one of the most punchable characters ever.
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