西鲁瑞韦 | 300832-84-2

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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
• 中文名称: 西鲁瑞韦
• 英文名称: ciluprevir
• 英文别名: BILN 2061；(1S,4R,6S,7Z,14S,18R)-14-(cyclopentyloxycarbonylamino)-18-[7-methoxy-2-[2-(propan-2-ylamino)-1,3-thiazol-4-yl]quinolin-4-yl]oxy-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid
• CAS: 300832-84-2
• 化学式: C₄₀H₅₀N₆O₈S
• 分子量: 774.938
• InChiKey: PJZPDFUUXKKDNB-KNINVFKUSA-N

物化性质

• 密度：
  1.37
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  55
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  210
• 氢给体数：
  4
• 氢受体数：
  12

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(1S,4R,6S,7Z,14S,18R)-14-cyclopentyloxycarbonylamino-18-[2-(2-isopropylamino-thiazol-4-yl)-7-methoxy-quinolin-4-yloxy]-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid methyl ester	681145-22-2	C41H52N6O8S	788.965
  ——	(Z)-(1S,4R,6S,14S,18R)-14-Cyclopentyloxycarbonylamino-18-(7-methoxy-2-methoxycarbonyl-quinolin-4-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid methyl ester	300831-74-7	C37H46N4O10	706.793
  ——	(1S,4R,6S,14S,18R)-18-[2-(2-bromoacetyl)-7-methoxyquinolin-4-yloxy]-14-cyclopentyloxycarbonylamino-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid methyl ester	300831-77-0	C37H45BrN4O9	769.69
  ——	(Z)-(1S,4R,6S,14S,18R)-14-tert-Butoxycarbonylamino-18-(7-methoxy-2-methoxycarbonyl-quinolin-4-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid methyl ester	300831-72-5	C36H46N4O10	694.782
  ——	(1S,4R,6S,7Z,14S,18S)-18-(4-bromo-benzenesulfonyloxy)-14-cyclopentyloxycarbonylamino-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid methyl ester	782479-05-4	C31H40BrN3O9S	710.643
  ——	(1S,4R,6S,7Z,14S,18S)-14-cyclopentyloxycarbonylamino-18-(4-nitro-benzoyloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid methyl ester	912291-95-3	C32H40N4O10	640.69
  ——	(1S,2R)-1-{[(2S,4S)-4-(4-bromo-benzenesulfonyloxy)-1-((S)-2-cyclopentyloxycarbonylamino-oct-7-enoyl)pyrrolidine-2-carbonyl]-amino}-2-vinylcyclopropanecarboxylic acid methyl ester	769167-58-0	C33H44BrN3O9S	738.697
  ——	4-nitro-benzoic acid 1-(2-cyclopentyloxycarbonylamino-non-8-enoyl)-5-(1-methoxycarbonyl-2-vinylcyclopropylcarbamoyl)-pyrrolidin-3-yl ester	912291-94-2	C34H44N4O10	668.744
  ——	(1S,4R,6S,7Z,14S,18S)-14-cyclopentyloxycarbonylamino-18-hydroxy-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid methyl ester	912291-96-4	C25H37N3O7	491.585
  ——	methyl (2S,6S,12Z,13aS,14aR,16aS)-6-[(tert-butoxycarbonyl)amino]-2-hydroxy-5,16-dioxo-1,2,3,6,7,8,9,10,11,13a,14,15,16,16a-tetradecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a(5H)-carboxylate	300831-46-3	C24H37N3O7	479.574

反应信息

• 作为产物：
  描述：

  (Z)-(1S,4R,6S,14S,18R)-14-Cyclopentyloxycarbonylamino-18-(7-methoxy-2-methoxycarbonyl-quinolin-4-yloxy)-2,15-dioxo-3,16-diaza-tricyclo[14.3.0.0^4,6]nonadec-7-ene-4-carboxylic acid methyl ester 在 lithium hydroxide 、 sodium hydroxide 、 氢溴酸 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 水 、 异丙醇 为溶剂， 反应 19.75h， 生成 西鲁瑞韦
  参考文献：
  名称：

  Synthesis of BILN 2061, an HCV NS3 Protease Inhibitor with Proven Antiviral Effect in Humans

  摘要：

  The synthesis of BILN 2061, an NS3 protease inhibitor with proven antiviral effect in humans, was accomplished in a convergent manner from four building blocks. The procedure described here was suitable for the preparation of multigram quantities of BILN 2061 for preclinical pharmacological evaluation.

  DOI：

  10.1021/ol0489907

文献信息

• HCV PROTEASE INHIBITORS AND USES THEREOF
  申请人：Niu Deqiang

  公开号：US20090176858A1

  公开（公告）日：2009-07-09

  The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

  本发明提供了化合物、药学上可接受的组合物以及使用它们的方法。
• Sulfone-Mediated S_NAr Reaction as a Powerful Tool for the Synthesis of 4-Quinolinyl Ethers and More—Application to the Synthesis of HCV NS3/4a Protease Inhibitor <b>BI 201420</b>
  作者：Nitinchandra D. Patel、Xudong Wei、Denis Byrne、Bikshandarkoil A. Narayanan、Scott Pennino、Max Sarvestani、Anjan Saha、Nizar Haddad、Suresh Kapadia、Jon C. Lorenz、Philomen DeCroos、Andrew Ye、Heewon Lee、Nelu Grinberg、Azad Hossain、Carl A. Busacca、Nathan K. Yee、Chris H. Senanayake

  DOI：10.1021/acs.joc.0c00554

  日期：2020.7.2

  An efficient general methodology for the synthesis of 4-quinolinyl ethers is demonstrated via a highly reactive SNAr reaction of 4-quinolinyl sulfones with a range of structurally diversified 1°, 2°, and 3° alcohols with a wide substrate scope and high yields. By adapting this methodology, a convergent synthesis of a complex target of HCV NS3/4a protease inhibitor BI 201420 was accomplished.

  通过4-喹啉基砜与一系列结构多样的1°，2°和3°醇的高反应性S N Ar反应，证明了合成4-喹啉基醚的有效通用方法，该方法具有广泛的底物范围和较高的产量。通过采用这种方法，可以完成HCV NS3 / 4a蛋白酶抑制剂BI 201420复杂靶标的融合合成。
• Acylaminoheteroaryl hepatitis C virus protease inhibitors
  申请人：Niu Deqiang

  公开号：US20080039470A1

  公开（公告）日：2008-02-14

  The present invention discloses compounds of formulae I and II, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明揭示了式I和II的化合物，或其药用可接受的盐、酯或前药：这些化合物抑制丝氨酸蛋白酶活性，特别是乙型肝炎病毒（HCV）NS3-NS4A蛋白酶的活性。因此，本发明的化合物干扰了乙型肝炎病毒的生命周期，并且也可用作抗病毒剂。本发明还涉及包含上述化合物的药物组合物，用于给患有HCV感染的受试者进行治疗。本发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的HCV感染的方法。
• [EN] MACROCYCLIC PEPTIDES ACTIVE AGAINST THE HEPATITIS C VIRUS<br/>[FR] PEPTIDES MACROCYCLIQUES ACTIFS CONTRE LE VIRUS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2004037855A1

  公开（公告）日：2004-05-06

  Compounds of formula (I): wherein R1 is (C1-8)alkyl, (C3-7)cycloalkyl, (C1-6)alkyl-(C3-7)cycloalkyl} or Het, which are all optionally substituted from 1 to 3 times with halo, cyano, nitro, O-(C1-6)alkyl, amido, amino or phenyl, or R1 is C6 or C10 aryl which is optionally substituted from 1 to 3 times with halo, cyano, nitro, (C1-6)alkyl, O-(C1-6)alkyl, amido, amino or phenyl; or a pharmaceutically acceptable salt thereof, useful as an inhibitor of the HCV NS3 protease.

  化合物的式子（I）：其中R1是（C1-8）烷基，（C3-7）环烷基，(C1-6)烷基-(C3-7)环烷基}或Het，它们都可以从1到3次地用卤素，氰基，硝基，O-（C1-6）烷基，酰胺，氨基或苯基进行取代，或者R1是C6或C10芳基，它可以从1到3次地用卤素，氰基，硝基，（C1-6）烷基，O-（C1-6）烷基，酰胺，氨基或苯基进行取代；或其药学上可接受的盐，作为HCV NS3蛋白酶的抑制剂。
• Novel Process for the Preparation of Nonracemic Long Chain alpha-Amino Acid Derivatives
  申请人：Jia Lanqi

  公开号：US20090036708A1

  公开（公告）日：2009-02-05

  The present invention provides a process for the preparation of a nonracemic a-amino acid derivative from an optically active N-acyl lactam using an organometallic reagent to effect the opening of the ring followed by reduction of the ketone carbonyl to an alcohol or a methylene, or by a reductive amination to an amine, or by a ketalization reaction.

  本发明提供了一种从手性N-酰基内酰胺中使用有机金属试剂开环，随后还原酮羰基为醇或亚甲基，或通过还原胺基化为胺，或通过缩酮反应制备非外消旋α-氨基酸衍生物的方法。