(3S)-3-氨基-N-环丙基-2-羟基庚酰胺盐酸盐 | 1137141-25-3

• 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: (3S)-3-氨基-N-环丙基-2-羟基庚酰胺盐酸盐
• 英文名称: (S)-3-amino-2-hydroxy-heptanoic acid cyclopropylamide hydrochloride salt
• 英文别名: Heptanamide, 3-amino-N-cyclopropyl-2-hydroxy-, (Hydrochloride) (1:1), (3S)-；(3S)-3-amino-N-cyclopropyl-2-hydroxyheptanamide;hydrochloride
• CAS: 1137141-25-3
• 化学式: C₁₀H₂₀N₂O₂*ClH
• 分子量: 236.742
• InChiKey: IHYTVEIDGGVQQH-GUORDYTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.57
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  75.4
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S)-3-氨基-N-环丙基-2-羟基庚酰胺盐酸盐 、 (1R,2S,5S)-3-((S)-2-(3-(1-((叔丁基磺酰基)甲基)环己基)脲基)- 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 生成 (1R,2S,5S)-3-((S)-2-(3-(1-((叔丁基磺酰基)甲基)环己基)脲基)-
  参考文献：
  名称：

  Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor

  摘要：

  Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (similar to 10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.

  DOI：

  10.1021/ml9000276
• 作为产物：
  描述：

  (3S)-3-((tert-butoxycarbonyl)amino)-1-(cyclopropylamino)-1-oxoheptan-2-yl acetate 在 水 、 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 (3S)-3-氨基-N-环丙基-2-羟基庚酰胺盐酸盐
  参考文献：
  名称：

  Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor

  摘要：

  Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (similar to 10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.

  DOI：

  10.1021/ml9000276

文献信息

• [EN] SULFUR COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE<br/>[FR] COMPOSES SOUFRES EN TANT QU'INHIBITEURS DE LA PROTEASE SERINE NS3 DU VIRUS DE L'HEPATITE C
  申请人：SCHERING CORP

  公开号：WO2005087731A1

  公开（公告）日：2005-09-22

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明揭示了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一实施例中，本发明揭示了包含这些化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Cyclic Sulfones as Novel P3-Caps for Hepatitis C Virus NS3/4A (HCV NS3/4A) Protease Inhibitors: Synthesis and Evaluation of Inhibitors with Improved Potency and Pharmacokinetic Profiles
  作者：Francisco Velázquez、Mousumi Sannigrahi、Frank Bennett、Raymond G. Lovey、Ashok Arasappan、Stéphane Bogen、Latha Nair、Srikanth Venkatraman、Melissa Blackman、Siska Hendrata、Yuhua Huang、Regina Huelgas、Patrick Pinto、Kuo-Chi Cheng、Xiao Tong、Andrew T. McPhail、F. George Njoroge

  DOI：10.1021/jm9016027

  日期：2010.4.22

  HCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to combat the infection. The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and efforts continue for the discovery of more potent compounds with improved pharmacokinetic profiles. A new series of HCV NS3 protease inhibitors having a cyclic sulfone P3-cap have been discovered. Compounds 43 and 44 showed K-i* values in the single-digit nM range and their cellular potency was improved by 10-fold compared to 1. The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration.
• WO2007/5838
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of potent sulfonamide P4-capped ketoamide second generation inhibitors of hepatitis C virus NS3 serine protease with favorable pharmacokinetic profiles in preclinical species
  作者：Stéphane L. Bogen、Ashok Arasappan、Francisco Velazquez、Melissa Blackman、Regina Huelgas、Weidong Pan、Elise Siegel、Latha G. Nair、Srikanth Venkatraman、Zhuyan Guo、Ronald Doll、Neng-Yang Shih、F. George Njoroge

  DOI：10.1016/j.bmc.2010.01.044

  日期：2010.3

  Hepatitis is a disease characterized by inflammation of the liver, usually producing swelling and, in many cases, permanent damage to liver tissues. Viral hepatitis C (HCV), a small (+)-RNA virus, infects chronically 3% of the world's population. Boceprevir, SCH 503034, (1) our first generation HCV inhibitor, has already established proof-of-concept and is currently in late stage (phase III) clinical trials. In view of the positive data from our first generation compound, further work aimed at optimizing its overall profile was undertaken. Herein, we report that extension of our earlier inhibitor to the P-4 pocket by introducing a new sulfonamide moiety and optimization of the P1/P-1' capping led to the discovery of a novel series of inhibitors of the HCV NS3 serine protease. Optimization of the P-1 residue significantly improved potency and selectivity. The combination of optimal moieties led to the discovery of compound 47 which, in addition to being a potent inhibitor of HCV subgenomic RNA replication, was also found to have good PK profile in rat, dog and monkey. (C) 2010 Elsevier Ltd. All rights reserved.
• Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor
  作者：Ashok Arasappan、Frank Bennett、Stephane L. Bogen、Srikanth Venkatraman、Melissa Blackman、Kevin X. Chen、Siska Hendrata、Yuhua Huang、Regina M. Huelgas、Latha Nair、Angela I. Padilla、Weidong Pan、Russell Pike、Patrick Pinto、Sumei Ruan、Mousumi Sannigrahi、Francisco Velazquez、Bancha Vibulbhan、Wanli Wu、Weiying Yang、Anil K. Saksena、Viyyoor Girijavallabhan、Neng-Yang Shih、Jianshe Kong、Tao Meng、Yan Jin、Jesse Wong、Paul McNamara、Andrew Prongay、Vincent Madison、John J. Piwinski、Kuo-Chi Cheng、Richard Morrison、Bruce Malcolm、Xiao Tong、Robert Ralston、F. George Njoroge

  DOI：10.1021/ml9000276

  日期：2010.5.13

  Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (similar to 10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.