((R)-1-{(S)-2-[(2-Amino-thiazol-4-ylmethyl)-carbamoyl]-pyrrolidine-1-carbonyl}-2,2-dicyclohexyl-ethyl)-carbamic acid tert-butyl ester | 197893-48-4

• 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: ((R)-1-{(S)-2-[(2-Amino-thiazol-4-ylmethyl)-carbamoyl]-pyrrolidine-1-carbonyl}-2,2-dicyclohexyl-ethyl)-carbamic acid tert-butyl ester
• 英文别名: ((R)-2-{(S)-2-[(2-Amino-thiazol-4-ylmethyl)-carbamoyl]-pyrrolidin-1-yl}-1-dicyclohexylmethyl-2-oxo-ethyl)-carbamic acid tert-butyl ester；tert-butyl N-[(2R)-1-[(2S)-2-[(2-amino-1,3-thiazol-4-yl)methylcarbamoyl]pyrrolidin-1-yl]-3,3-dicyclohexyl-1-oxopropan-2-yl]carbamate
• CAS: 197893-48-4
• 化学式: C₂₉H₄₇N₅O₄S
• 分子量: 561.789
• InChiKey: GBZBLLVKJIQDQX-LADGPHEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ((R)-1-{(S)-2-[(2-Amino-thiazol-4-ylmethyl)-carbamoyl]-pyrrolidine-1-carbonyl}-2,2-dicyclohexyl-ethyl)-carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 (S)-1-((R)-2-Amino-3,3-dicyclohexyl-propionyl)-pyrrolidine-2-carboxylic acid (2-amino-thiazol-4-ylmethyl)-amide
  参考文献：
  名称：

  Discovery of a Novel, Selective, and Orally Bioavailable Class of Thrombin Inhibitors Incorporating Aminopyridyl Moieties at the P1 Position

  摘要：

  A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (K-i 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral Fl was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at Fl was a key step in our search for a clinical candidate.

  DOI：

  10.1021/jm970493r
• 作为产物：
  描述：

  Boc-D-Ala(dicHex)-Pro-OMe 在 lithium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 8.5h， 生成 ((R)-1-{(S)-2-[(2-Amino-thiazol-4-ylmethyl)-carbamoyl]-pyrrolidine-1-carbonyl}-2,2-dicyclohexyl-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of a Novel, Selective, and Orally Bioavailable Class of Thrombin Inhibitors Incorporating Aminopyridyl Moieties at the P1 Position

  摘要：

  A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (K-i 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral Fl was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at Fl was a key step in our search for a clinical candidate.

  DOI：

  10.1021/jm970493r