(2S,4R)-1-((S)-2-tert-butyl-4-oxo-4-(piperidin-1-yl)butanoyl)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)-4-(6-methoxy-3-phenylisoquinolin-1-yloxy)pyrrolidine-2-carboxamide | 1001667-23-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,4R)-1-((S)-2-tert-butyl-4-oxo-4-(piperidin-1-yl)butanoyl)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)-4-(6-methoxy-3-phenylisoquinolin-1-yloxy)pyrrolidine-2-carboxamide
• 英文别名: sovaprevir；(2S,4R)-1-((S)-2-tert-butyl-4-oxo-4-(piperidin-1-yl)butanoyl)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)-4-(7-methoxy-2-phenylquinolin-4-yloxy)pyrrolidine-2-carboxamide；(2S,4R)-N-[(1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-ethenylcyclopropyl]-1-[(2S)-3,3-dimethyl-2-(2-oxo-2-piperidin-1-ylethyl)butanoyl]-4-(7-methoxy-2-phenylquinolin-4-yl)oxypyrrolidine-2-carboxamide
• CAS: 1001667-23-7
• 化学式: C₄₃H₅₃N₅O₈S
• 分子量: 799.989
• InChiKey: MHFMTUBUVQZIRE-WINRQGAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  57
• 可旋转键数：
  14
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  173
• 氢给体数：
  2
• 氢受体数：
  9

制备方法与用途

Sofaprevir（ACH-1625，ACH-0141625）是一种强效的HCV NS3/4A抑制剂，目前正在用于治疗丙型肝炎的临床开发中。

反应信息

• 作为产物：
  描述：

  methyl (2S,4S)-4-(4-bromophenyl)sulfonyloxy-1-[(2S)-3,3-dimethyl-2-(2-oxo-2-piperidin-1-ylethyl)butanoyl]pyrrolidine-2-carboxylate 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 (2S,4R)-1-((S)-2-tert-butyl-4-oxo-4-(piperidin-1-yl)butanoyl)-N-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropyl)-4-(6-methoxy-3-phenylisoquinolin-1-yloxy)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  [EN] PROCESSES FOR PRODUCING SOVAPREVIR
  [FR] PROCESSUS INNOVANTS DE PRODUCTION DE SOVAPREVIR

  摘要：

  公开号：

  WO2014152928A3

文献信息

• 4-AMINO-4-OXOBUTANOYL PEPTIDES AS INHIBITORS OF VIRAL REPLICATION
  申请人：Phadke Avinash

  公开号：US20090048297A1

  公开（公告）日：2009-02-19

  The invention provides 4-amino-4-oxobutanoyl peptide compounds of Formula I and the pharmaceutically salts and hydrates thereof. The variables R 1 -R 9 , R 16 , R 18 , R 19 , n, M, n, M, and Z are defined herein. Certain compounds of Formula I are useful as antiviral agents. Certain 4-amino-4-oxobutanoyl peptide compounds disclosed herein are potent and/or selective inhibitors of viral replication, particularly Hepatitis C virus replication. The invention also provides pharmaceutical compositions containing one or more 4-amino-4-oxobutanoyl peptide compounds and one or more pharmaceutically acceptable carriers. Such pharmaceutical compositions may contain 4-amino-4-oxobutanoyl peptide compound as the only active agent or may contain a combination of 4-amino-4-oxobutanoyl peptide containing peptides compound and one or more other pharmaceutically active agents. The invention also provides methods for treating viral infections, including Hepatitis C infections, in mammals.

  该发明提供了Formula I的4-氨基-4-氧代丁酰肽化合物及其药用盐和水合物。变量R1-R9、R16、R18、R19、n、M和Z在此处定义。Formula I的某些化合物可用作抗病毒剂。本文披露的某些4-氨基-4-氧代丁酰肽化合物是有效和/或选择性抑制病毒复制的药物，特别是乙型肝炎病毒的复制。该发明还提供含有一种或多种4-氨基-4-氧代丁酰肽化合物和一种或多种药用载体的药物组合物。这种药物组合物可能仅含有4-氨基-4-氧代丁酰肽化合物作为唯一活性剂，也可能含有一种或多种其他药用活性剂与含有4-氨基-4-氧代丁酰肽的肽化合物的组合。该发明还提供了治疗哺乳动物病毒感染的方法，包括乙型肝炎感染。
• [EN] HEPATITIS C INHIBITOR TRI-PEPTIDES<br/>[FR] TRI-PEPTIDES INHIBITEURS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM CA LTD

  公开号：WO2000009543A2

  公开（公告）日：2000-02-24

  Racemates, diastereoisomers and optical isomers of a compound of formula (I) wherein B is H, a C6 or C10 aryl, C7-16 aralkyl; Het or (lower alkyl)-Het, all of which optionally substituted with C1-6 alkyl; C1-6 alkoxy; C1-6 alkanoyl; hydroxy; hydroxyalkyl; halo; haloalkyl; nitro; cyano; cyanoalkyl; amino optionally substituted with C1-6 alkyl; amido; or (lower alkyl)amide; or B is an acyl derivative of formula R4-C(O)-; a carboxyl of formula R4-O-C(O)-; an amide of formula R4-N(R5)-C(O)-; a thioamide of formula R4-N(R5)-C(S)-;or a sulfonyl of formula R4-SO2; R5 is H or C1-6 alkyl; and Y is H or C1-6 alkyl; R3 is C¿1-8? alkyl, C3-7 cycloalkyl, or C4-10 alkylcycloalkyl, all optionally substituted with hydroxy, C1-6 alkoxy, C1-6 thioalkyl, amido, (lower alkyl)amido, C6 or C10 aryl, or C7-16 aralkyl; R2 is CH2-R20, NH-R20, O-R20or S-R20, wherein R20 is a saturated or unsaturated C3-7 cycloalkyl or C4-10 (alkylcycloalkyl), all of which being optionally mono-, di- or tri-substituted with R21, or R20 is a C6 or C10 aryl or C7-14 aralkyl optionally substituted, or R20 is Het or (lower alkyl)-Het, both optionally substituted, Het or (lower alkyl)-Het; carboxyl; carboxy(lower alkyl); C6 or C10 aryl, C7-14 aralkyl or Het, said aryl, aralkyl or Het being optionally substituted; and R?1¿ is H; C¿1-6? alkyl, C3-7 cycloalkyl, C2-6 alkenyl, or C2-6 alkynyl, all optionally substituted with halogen; or a pharmaceutically acceptable salt or ester thereof.

  化合物式（I）的同分异构体、对映异构体和光学异构体，其中B为H、C6或C10芳基、C7-16芳基烷基；Het或（较低烷基）-Het，所有这些都可以用C1-6烷基、C1-6烷氧基、C1-6烷酰基、羟基、羟基烷基、卤素、卤素烷基、硝基、氰基、氰基烷基、氨基（可选用C1-6烷基取代）、酰胺或（较低烷基）酰胺、或B是公式R4-C（O）-的酰衍生物；公式R4-O-C（O）-的羧基；公式R4-N（R5）-C（O）-的酰胺；公式R4-N（R5）-C（S）-的硫酰胺；或公式R4-SO2的磺酰基；R5为H或C1-6烷基；Y为H或C1-6烷基；R3为C1-8烷基、C3-7环烷基或C4-10烷基环烷基，所有这些都可以用羟基、C1-6烷氧基、C1-6硫代烷基、酰胺、（较低烷基）酰胺、C6或C10芳基或C7-16芳基烷基取代；R2为CH2-R20、NH-R20、O-R20或S-R20，其中R20为饱和或不饱和的C3-7环烷基或C4-10（烷基环烷基），所有这些都可以选择性地单、双或三取代R21，或者R20是C6或C10芳基或C7-14芳基烷基，可以选择性地取代，或者R20是Het或（较低烷基）-Het，两者都可以选择性地取代，Het或（较低烷基）-Het；羧基；羧基（较低烷基）；C6或C10芳基、C7-14芳基烷基或Het，所述芳基、芳基烷基或Het均可选择性地取代；以及R1为H；C1-6烷基、C3-7环烷基、C2-6烯基或C2-6炔基，所有这些都可以选择性地取代卤素；或其药学上可接受的盐或酯。
• Processes for Producing sovaprevir
  申请人：Achillion Pharmaceuticals, Inc.

  公开号：US09115175B2

  公开（公告）日：2015-08-25

  The disclosure includes novel processes for producing Sovaprevir comprising adding compound E to F-1 to provide Sovaprevir. The disclosure further includes intermediates useful for producing Sovaprevir. The disclosure also include a novel crystalline form of Sovaprevir, Form F, and a method for preparing spray-dried amorphous Sovaprevir from crystalline Form F.

  本公开涉及生产Sovaprevir的新工艺，包括添加E化合物到F-1中以得到Sovaprevir。本公开还包括用于生产Sovaprevir的中间体。本公开还包括Sovaprevir的新晶体形式F，以及从晶体形式F制备喷雾干燥非晶态Sovaprevir的方法。
• 4-amino-4-oxobutanoyl Peptides as Inhibitors of Viral Replication
  申请人：Achillion Pharmaceuticals, Inc.

  公开号：EP2374812A2

  公开（公告）日：2011-10-12

  The invention provides 4-amino-4-oxobutanoyl peptide compounds of Formula I and the pharmaceutically salts and hydrates thereof. The variables R1-R9, R16, R18, R19, n, M, , n, M, , and Z are defined herein. Certain compounds of Formula I are useful as antiviral agents. Certain 4-amino-4-oxobutanoyl peptide compounds disclosed herein are potent and/ or selective inhibitors of viral replication, particularly Hepatitis C virus replication. The invention also provides pharmaceutical compositions containing one or more 4-amino-4-oxobutanoyl peptide compounds and one or more pharmaceutically acceptable carriers. Such pharmaceutical compositions may contain 4-amino-4-oxobutanoyl peptide compound as the only active agent or may contain a combination of 4-amino-4-oxobutanoyl peptide containing peptides compound and one or more other pharmaceutically active agents. The invention also provides methods for treating viral infections, including Hepatitis C infections, in mammals.

  本发明提供了式 I 的 4-氨基-4-氧代丁酰基肽化合物 及其药用盐和水合物。 变量 R1-R9、R16、R18、R19、n、M、、n、M、和 Z 在本文中定义。某些式 I 化合物可用作抗病毒剂。本文公开的某些 4-氨基-4-氧代丁酰基肽化合物是病毒复制，特别是丙型肝炎病毒复制的强效和/或选择性抑制剂。本发明还提供了含有一种或多种 4-氨基-4-氧代丁酰基肽化合物和一种或多种药学上可接受的载体的药物组合物。这种药物组合物可以含有4-氨基-4-氧代丁酰基肽化合物作为唯一的活性剂，也可以含有含4-氨基-4-氧代丁酰基肽化合物和一种或多种其他药物活性剂的组合。本发明还提供了治疗哺乳动物病毒感染（包括丙型肝炎感染）的方法。
• Chimeric antigen receptor (CAR) modulation
  申请人：TRUSTEES OF BOSTON UNIVERSITY

  公开号：US11059864B2

  公开（公告）日：2021-07-13

  The technology described herein is directed to CAR polypeptides and systems comprising repressible proteases. In combination with a specific protease inhibitor, the activity of said CAR polypeptides and systems and cells comprising them can be modulated. Also described herein are methods of using said CAR polypeptides and systems, for example to treat various diseases and disorders.

  本文所述技术针对的是包含可抑制蛋白酶的 CAR 多肽和系统。结合特定的蛋白酶抑制剂，可以调节所述 CAR 多肽和系统以及包含它们的细胞的活性。本文还描述了使用所述 CAR 多肽和系统的方法，例如用于治疗各种疾病和失调。