4(S)-(1-methylethyl)-3-<1-oxo-3-<2-<<(2,2,2-trichloroethoxy)carbonyl>amino>-4-thiazolyl>propyl>-2-oxazolidinone | 160447-19-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4(S)-(1-methylethyl)-3-<1-oxo-3-<2-<<(2,2,2-trichloroethoxy)carbonyl>amino>-4-thiazolyl>propyl>-2-oxazolidinone
• 英文别名: 4(S)-(1-Methylethyl)-3-{3-{2-[(2,2,2-trichloroethoxy)carbonylamino]-4-thiazolyl}-1-oxopropyl}-2-oxazolidinone；2,2,2-trichloroethyl N-[4-[3-oxo-3-[(4S)-2-oxo-4-propan-2-yl-1,3-oxazolidin-3-yl]propyl]-1,3-thiazol-2-yl]carbamate
• CAS: 160447-19-8
• 化学式: C₁₅H₁₈Cl₃N₃O₅S
• 分子量: 458.75
• InChiKey: DCYUBHVYQUADSD-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4(S)-(1-methylethyl)-3-<1-oxo-3-<2-<<(2,2,2-trichloroethoxy)carbonyl>amino>-4-thiazolyl>propyl>-2-oxazolidinone 在 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 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.25h， 生成 {4-[(R)-2-{[Dimethylcarbamoylmethyl-(1-hydroxy-cyclohexylmethyl)-carbamoyl]-methyl}-3-((S)-4-isopropyl-2-oxo-oxazolidin-3-yl)-3-oxo-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
• 作为产物：
  描述：

  3-(3-carboxy-1-oxopropyl)-4(S)-(1-methylethyl)-2-oxazolidinone 在 4-二甲氨基吡啶 、 草酰氯 、 氢溴酸 、 N,N-二异丙基乙胺 、 硫脲 作用下， 以 四氢呋喃 、 二氯甲烷 、 异丙醇 为溶剂， 反应 21.17h， 生成 4(S)-(1-methylethyl)-3-<1-oxo-3-<2-<<(2,2,2-trichloroethoxy)carbonyl>amino>-4-thiazolyl>propyl>-2-oxazolidinone
  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

文献信息

• Renin Inhibiting N-(2-Amino-2-oxoethyl)Butanediamide Derivatives
  申请人：BIO-MEGA/BOEHRINGER INGELHEIM RESEARCH INC.

  公开号：EP0589445A1

  公开（公告）日：1994-03-30

  Disclosed herein are compounds of the formula:         A-N(R¹)C(O)CH₂CHR²C(O)-B wherein A is R³R⁴NC(O)CH₂ wherein, for example, R³ is hydrogen or alkyl and R⁴ is hydrogen, alkyl or a substituted alkyl such as 2-(2-pyridinyl)ethyl, or R³ and R⁴ together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, morpholino or thiomorpholino; R¹ is, for example, benzyl, alkyl or a substituted alkyl such as cyclohexylmethyl; R² is, for example, alkyl, cycloalkylmethyl, 1H-imidazol-4-ylmethyl, 4-thiazolylmethyl or (2-amino-4-thiazolyl)methyl; and B is a renin substrate transition state analog, for example, [1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl]amino. The compounds inhibit renin activity and are indicated for the treatment of hypertension and congestive heart failure.

  这里公开的是式中的化合物： A-N(R¹)C(O)CH₂CHR²C(O)-B 其中 A 是 R³R⁴NC(O)CH₂，例如，R³是氢或烷基，R⁴是氢、烷基或取代的烷基，如 2-(2-吡啶基)乙基，或 R³ 和 R⁴ 与它们所连接的氮原子一起形成吡咯烷基、哌啶基、吗啉基或硫代吗啉基；R¹例如是苄基、烷基或取代的烷基，如环己基甲基；R²例如是烷基、环烷基甲基、1H-咪唑-4-基甲基、4-噻唑基甲基或（2-氨基-4-噻唑基）甲基；B是肾素底物过渡态类似物，例如[1(S)-(环己基甲基)-2(R),3(S)-二羟基-5-甲基己基]氨基。这些化合物可抑制肾素活性，适用于治疗高血压和充血性心力衰竭。
• N-(Hydroxyethyl)butanediamide derivatives as renin inhibitors
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：EP0589446B1

  公开（公告）日：1997-09-03
• US5523315A
  申请人：——

  公开号：US5523315A

  公开（公告）日：1996-06-04
• US5541163A
  申请人：——

  公开号：US5541163A

  公开（公告）日：1996-07-30
• US5554634A
  申请人：——

  公开号：US5554634A

  公开（公告）日：1996-09-10