2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-2-hydroxyacetic acid | 1352817-95-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-2-hydroxyacetic acid
• 英文别名: 2-(1-{[(Tert-butoxy)carbonyl]amino}cyclopropyl)-2-hydroxyacetic acid；2-hydroxy-2-[1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropyl]acetic acid
• CAS: 1352817-95-8
• 化学式: C₁₀H₁₇NO₅
• 分子量: 231.249
• InChiKey: LBZPEYHHWMRRMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-2-hydroxyacetic acid 在 甲醇 、 乙酰氯 作用下， 以 hexanes 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  [EN] NEW CATHEPSIN S PROTEASE INHIBITORS, USEFUL IN THE TREATMENT OF E.G. AUTOIMMUNE DISORDERS, ALLERGY AND CHRONIC PAIN CONDITIONS
  [FR] NOUVEAUX INHIBITEURS DE CATHEPSINE S PROTÉASE, UTILES DANS LE TRAITEMENT, PAR EX., DE MALADIES AUTO-IMMUNES, D'ALLERGIES ET DE DOULEURS CHRONIQUES

  摘要：

  式（I）的化合物，其中R2a和R2b分别为H、卤素、C1-C4烷基、C1-C4卤代烷基或C1-C4烷氧基，或者R2a和R2b与它们连接的碳原子一起形成C3-C6环烷基；R3为C5-C10烷基，可选择地用1-3个卤素、C1-C4卤代烷基、C1-C4烷氧基、C1-C4卤代烷氧基取代；或者R3为至少有2个氯或3个氟取代基的C2-C4烷基链；或者R3为C3-C7环烷基甲基，可选择地用1-3个C1-C4烷基、卤素、C1-C4卤代烷基、C1-C4烷氧基、C1-C4卤代烷氧基取代；R4为C1-C6烷基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6卤代烷氧基、C1-C6烷基氨基、C1-C6二烷基氨基或者；R4为Het或Carbocyclyl，其中任一者可选择地用1-3个取代基取代；n为1、2或3；用于预防或治疗以胰蛋白酶S的不适当表达或活化为特征的疾病。

  公开号：

  WO2011158197A1
• 作为产物：
  描述：

  methyl 2-hydroxy-2-[1-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopropyl]acetate 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-2-hydroxyacetic acid
  参考文献：
  名称：

  Potent ketoamide inhibitors of HCV NS3 protease derived from quaternized P1 groups

  摘要：

  Blood borne hepatitis C infections are the primary cause for liver cirrhosis and hepatocellular carcinoma. HCV NS3 protease, a pivotal enzyme in the replication cycle of HCV virus has been the primary target for development of new drug candidates. Boceprevir and telaprevir are two novel ketoamide derived inhibitors that are currently undergoing phase-III clinical trials. These inhibitors include ketoamide functionality as serine trap and have an acidic alpha-ketoamide center that undergoes epimerization under physiological conditions. Our initial attempts to arrest this epimerization by introducing quaternary amino acids at P-1 had resulted in significantly diminished activity. In this manuscript we describe alpha quaternized P-1 group that result in potent inhibitors in the enzyme assay and demonstrate cellular activity comparable to boceprevir. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.02.051

文献信息

• [EN] CYSTEINE PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA CYSTÉINE PROTÉASE
  申请人：MEDIVIR UK LTD

  公开号：WO2012172473A1

  公开（公告）日：2012-12-20

  Compounds of the formula (I) wherein One of A1 and A2 is N-CH3 and the other is CH; R1 is C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl or oxetan-3-yl, wherein C3-C6cycloalkyl is optionally substituted with one, two or three fluoro or with CF3; R2a and R2b are independently selected from H, halo, C1-C4alkyl, C1-C4haloalkyl and C1- C4alkoxy; R3 is CH3 or F; n is 1, 2, 3 or 4; or a pharmaceutically acceptable salt, hydrate or N-oxide thereof for the use in the prophylaxis and/or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

  式(I)的化合物，其中A1和A2中的一个是N-CH3，另一个是CH；R1是C1-C6烷基，C1-C6卤代烷基，C3-C6环烷基或氧杂环丙烷-3-基，其中C3-C6环烷基可选择地用一个、两个或三个氟代基或CF3取代；R2a和R2b分别选自H、卤素、C1-C4烷基、C1-C4卤代烷基和C1-C4烷氧基；R3是CH3或F；n为1、2、3或4；或其药学上可接受的盐、水合物或N-氧化物，用于预防和/或治疗由于cathepsin S的不适当表达或激活而表现出的疾病。
• CYSTEINE PROTEASE INHIBITORS
  申请人：Ayesa Susana

  公开号：US20130172232A1

  公开（公告）日：2013-07-04

  Compounds of the formula I wherein R 2a and R 2b are independently H, halo, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or C 1 -C 4 alkoxy, or R 2a and R 2b together with the carbon atom to which they are attached form a C 3 -C 6 cycloalkyl; R 3 is a C 5 -C 10 alkyl, optionally substituted with 1-3 substituents independently selected from halo, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; or R 3 is a C 2 -C 4 alkyl chain with at least 2 chloro or 3 fluoro substituents; or R 3 is C 3 -C 7 cycloalkylmethyl, optionally substituted with 1-3 substituents independently selected from C 1 -C 4 alkyl, halo, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy; R 4 is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylamino, C 1 -C 6 dialkylamino or; R 4 is Het or Carbocyclyl, either of which is optionally substituted with 1-3 substituents R 4 is Het, carbocyclyl, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 1 -C 6 haloalkoxy; n is 1, 2 or 3; for the use in the prophylaxis or treatment of a disorder characterised by inappropriate expression or activation of cathepsin S.

  化合物的公式为I，其中R2a和R2b独立地为H、卤素、C1-C4烷基、C1-C4卤代烷基或C1-C4烷氧基，或者R2a和R2b与它们连接的碳原子一起形成C3-C6环烷基；R3是C5-C10烷基，可选地被1-3个卤素、C1-C4卤代烷基、C1-C4烷氧基或C1-C4卤代烷氧基独立地取代；或者R3是具有至少2个氯或3个氟取代基的C2-C4烷基链；或者R3是C3-C7环烷基甲基，可选地被1-3个C1-C4烷基、卤素、C1-C4卤代烷基、C1-C4烷氧基或C1-C4卤代烷氧基独立地取代；R4是C1-C6烷基、C1-C6卤代烷基、C1-C6烷氧基、C1-C6卤代烷氧基、C1-C6烷基氨基、C1-C6二烷基氨基或者R4是Het或Carbocyclyl，它们中的任意一个可选地被1-3个取代基取代，其中R4是Het、carbocyclyl、C1-C6烷基、C1-C6卤代烷基、C1-C6烷氧基或C1-C6卤代烷氧基；n为1、2或3；用于预防或治疗由于cathepsin S不适当的表达或激活而表现出的障碍。
• Cysteine protease inhibitors
  申请人：Medivir UK Ltd

  公开号：EP2752404A1

  公开（公告）日：2014-07-09

  There is provided a process for the preparation of a compound of formula III, comprising the step of oxidising the compound of formula 2b wherein n is 2; R2a and R2b are independently H or F; R3 is 1-methylcyclopentylmethyl or 1-fluorocyclopentylmethyl; R3' is CH3 or F; R4 is C1-C6alkyl, C1-C6haloalkyl or C3-C6cycloalkyl, wherein C3-C6cycloalkyl is optionally substituted with methyl, CF3 or one or two fluoro. Compounds and processes used in the preparation of a compound of formula III are also provided.

  提供了一种制备式 III 化合物的工艺，包括氧化式 2b 化合物的步骤 其中 n 为 2；R2a 和 R2b 独立地为 H 或 F；R3 为 1-甲基环戊基甲基或 1-氟环戊基甲基；R3' 为 CH3 或 F；R4 为 C1-C6 烷基、C1-C6 卤代烷基或 C3-C6 环烷基，其中 C3-C6 环烷基任选被甲基、CF3 或一或二氟取代。还提供了用于制备式 III 化合物的化合物和工艺。
• NEW CATHEPSIN S PROTEASE INHIBITORS, USEFUL IN THE TREATMENT OF E.G. AUTOIMMUNE DISORDERS, ALLERGY AND CHRONIC PAIN CONDITIONS
  申请人：Medivir UK Ltd

  公开号：EP2582660B1

  公开（公告）日：2015-07-22
• US8859505B2
  申请人：——

  公开号：US8859505B2

  公开（公告）日：2014-10-14