{4-[(R)-3-(Benzyl-dimethylcarbamoylmethyl-carbamoyl)-2-((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-propyl]-thiazol-2-yl}-carbamic acid 2,2,2-trichloro-ethyl ester | 225378-75-6

• 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: {4-[(R)-3-(Benzyl-dimethylcarbamoylmethyl-carbamoyl)-2-((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-propyl]-thiazol-2-yl}-carbamic acid 2,2,2-trichloro-ethyl ester
• CAS: 225378-75-6
• 化学式: C₃₆H₅₂Cl₃N₅O₇S
• 分子量: 805.263
• InChiKey: YAFXPPALKOLEBX-OEXBRQEPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.95
• 重原子数：
  52.0
• 可旋转键数：
  18.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  161.4
• 氢给体数：
  4.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  {4-[(R)-3-(Benzyl-dimethylcarbamoylmethyl-carbamoyl)-2-((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-propyl]-thiazol-2-yl}-carbamic acid 2,2,2-trichloro-ethyl ester 在 盐酸 、 锌 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 (2R)-2-[(2-amino-1,3-thiazol-4-yl)methyl]-N'-benzyl-N-[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]-N'-[2-(dimethylamino)-2-oxoethyl]butanediamide
  参考文献：
  名称：

  Discovery of non-peptidic P 2 –P 3 butanediamide renin inhibitors with high oral efficacy

  摘要：

  A new series of non-peptidic renin inhibitors having a 2-substituted butanediamide moiety at the P-2 and P-3 positions has been identified. The optimized inhibitors have IC50 values of 0.8 to 1.4 nM and 2.5 to 7.6 nM in plasma renin assays at pH 6.0 and 7.4, respectively. When evaluated in the normotensive cynomolgus monkey model, two of the most potent inhibitors were orally active at a dose as low as 3 mg/kg. These potent renin inhibitors are characterized by oral bioavailabilities of 40 and 89% in the cynomolgus monkey. Inhibitor 3z (BILA 2157 BS) was selected as candidate for pre-development. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00265-x
• 作为产物：
  描述：

  3-[3-(2-Amino-4-thiazolyl)-1-oxopropyl]-4(S)-(1-methylethyl)-2-oxazolidinone 在 4-二甲氨基吡啶 、 lithium hydroxide 、 双氧水 、 sodium hexamethyldisilazane 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 三氟乙酸 为溶剂， 反应 56.5h， 生成 {4-[(R)-3-(Benzyl-dimethylcarbamoylmethyl-carbamoyl)-2-((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-propyl]-thiazol-2-yl}-carbamic acid 2,2,2-trichloro-ethyl ester
  参考文献：
  名称：

  Discovery of non-peptidic P 2 –P 3 butanediamide renin inhibitors with high oral efficacy

  摘要：

  A new series of non-peptidic renin inhibitors having a 2-substituted butanediamide moiety at the P-2 and P-3 positions has been identified. The optimized inhibitors have IC50 values of 0.8 to 1.4 nM and 2.5 to 7.6 nM in plasma renin assays at pH 6.0 and 7.4, respectively. When evaluated in the normotensive cynomolgus monkey model, two of the most potent inhibitors were orally active at a dose as low as 3 mg/kg. These potent renin inhibitors are characterized by oral bioavailabilities of 40 and 89% in the cynomolgus monkey. Inhibitor 3z (BILA 2157 BS) was selected as candidate for pre-development. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00265-x