N-[(1R,2S,5S)-5-(tert-butylcarbamoyl)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide | 773840-38-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-[(1R,2S,5S)-5-(tert-butylcarbamoyl)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide
• 英文别名: N-[(1R,2S,5S)-5-(tert-butylcarbamoyl)-2-[(5-chloro-1H-indole-2-carbonyl)amino]cyclohexyl]-5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-2-carboxamide
• CAS: 773840-38-3
• 化学式: C₂₈H₃₅ClN₆O₃S
• 分子量: 571.143
• InChiKey: WBPYJSSVYPJIFA-PAXLWEDBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(1R,2S,5S)-5-(tert-butylcarbamoyl)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide 在 盐酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 以89.2 mg的产率得到N-[(1R,2S,5S)-5-(tert-butylcarbamoyl)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride
  参考文献：
  名称：

  Discovery of N-[(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(dimethylcarbamoyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride: A novel, potent and orally active direct inhibitor of factor Xa

  摘要：

  In the early 1990's, we reported on the low-molecular selective fXa inhibitor DX-9065a having two amidino groups. However, it had poor oral bioavailability due to its strong basic amidino groups. To obtain fXa inhibitors with improved oral bioavailability, we investigated various non-amidino fXa inhibitors and finally discovered cis-1,2-diaminocyclohexane derivative 4c to have potent fXa inhibition, promising anticoagulant activity, and good oral bioavailability, compared with amidino compound DX-9065a. In addition, we will discuss the influence of the third substituent on the cyclohexane ring on anti-fXa activity, anticoagulant activity, PK profile, and lipophilicity. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.037
• 作为产物：
  描述：

  tert-butyl [(1R,2S,5S)-5-(tert-butylcarbamoyl)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]carbamate 、 lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate 在 盐酸 、 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 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 N-[(1R,2S,5S)-5-(tert-butylcarbamoyl)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Discovery of N-[(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(dimethylcarbamoyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride: A novel, potent and orally active direct inhibitor of factor Xa

  摘要：

  In the early 1990's, we reported on the low-molecular selective fXa inhibitor DX-9065a having two amidino groups. However, it had poor oral bioavailability due to its strong basic amidino groups. To obtain fXa inhibitors with improved oral bioavailability, we investigated various non-amidino fXa inhibitors and finally discovered cis-1,2-diaminocyclohexane derivative 4c to have potent fXa inhibition, promising anticoagulant activity, and good oral bioavailability, compared with amidino compound DX-9065a. In addition, we will discuss the influence of the third substituent on the cyclohexane ring on anti-fXa activity, anticoagulant activity, PK profile, and lipophilicity. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.037

文献信息

• ETHYLENEDIAMINE DERIVATIVES
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1270557B1

  公开（公告）日：2012-07-25
• US7192968B2
  申请人：——

  公开号：US7192968B2

  公开（公告）日：2007-03-20
• US7935824B2
  申请人：——

  公开号：US7935824B2

  公开（公告）日：2011-05-03