(S)-7-Amino-3-benzyloxycarbonylamino-2-hydroxy-heptanoic acid methyl ester | 1047403-21-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-7-Amino-3-benzyloxycarbonylamino-2-hydroxy-heptanoic acid methyl ester
• 英文别名: methyl (3S)-7-amino-2-hydroxy-3-(phenylmethoxycarbonylamino)heptanoate
• CAS: 1047403-21-3
• 化学式: C₁₆H₂₄N₂O₅
• 分子量: 324.377
• InChiKey: NVASESYSXJRGRL-LSLKUGRBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-7-Amino-3-benzyloxycarbonylamino-2-hydroxy-heptanoic acid methyl ester 在 10percent Pd/C 盐酸 、 sodium hydroxide 、 氢气 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 7-Amino-3-({1-[2-(carboxymethyl-amino)-3-cyclohexyl-propionyl]-3,3-dimethyl-pyrrolidine-2-carbonyl}-amino)-2-oxo-heptanoic acid
  参考文献：
  名称：

  Unique Overlap in the Prerequisites for Thrombin Inhibition and Oral Bioavailability Resulting in Potent Oral Antithrombotics

  摘要：

  Despite intense research over the last 10 years, aided by the availability of X-ray structures of enzyme-inhibitor complexes, only very few truly orally active thrombin inhibitors have been found. We conducted a comprehensive study starting with peptide transition state analogues (TSA). Both hydrophobic nonpeptide analogues as well as hydrophilic peptidic analogues were synthesized. The bioavailability in rats and dogs could be drastically altered depending on the overall charge distribution in the molecule. Compound 27, a tripeptide TSA inhibitor of thrombin, showed an oral bioavailability of 32% in rats and 71% in dogs, elimination half-lives being 58 and 108 min, respectively. The thrombin inhibition constant of compound 27 was 1.1 nM, and in an in vivo arterial flow model, the ED50 was 5.4 nmol/kg(.)min, comparable to known non-TSA inhibitors. A molecular design was found that combines antithrombotic efficiency with oral bioavailability at low dosages.

  DOI：

  10.1021/jm011110z
• 作为产物：
  描述：

  Nε-Boc-Nα-Cbz-L-赖氨酸 在 盐酸 、 苄基三乙基氯化铵 、 二异丁基氢化铝 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三乙胺 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 (S)-7-Amino-3-benzyloxycarbonylamino-2-hydroxy-heptanoic acid methyl ester
  参考文献：
  名称：

  Unique Overlap in the Prerequisites for Thrombin Inhibition and Oral Bioavailability Resulting in Potent Oral Antithrombotics

  摘要：

  Despite intense research over the last 10 years, aided by the availability of X-ray structures of enzyme-inhibitor complexes, only very few truly orally active thrombin inhibitors have been found. We conducted a comprehensive study starting with peptide transition state analogues (TSA). Both hydrophobic nonpeptide analogues as well as hydrophilic peptidic analogues were synthesized. The bioavailability in rats and dogs could be drastically altered depending on the overall charge distribution in the molecule. Compound 27, a tripeptide TSA inhibitor of thrombin, showed an oral bioavailability of 32% in rats and 71% in dogs, elimination half-lives being 58 and 108 min, respectively. The thrombin inhibition constant of compound 27 was 1.1 nM, and in an in vivo arterial flow model, the ED50 was 5.4 nmol/kg(.)min, comparable to known non-TSA inhibitors. A molecular design was found that combines antithrombotic efficiency with oral bioavailability at low dosages.

  DOI：

  10.1021/jm011110z

文献信息

• [EN] CYCLIC KETO-AMIDE COMPOUNDS AS CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF<br/>[FR] COMPOSÉS CÉTO-AMIDES CYCLIQUES UTILISÉS EN TANT QUE MODULATEURS DE LA CALPAÏNE, ET LEURS PROCÉDÉS DE PRODUCTION ET D'UTILISATION
  申请人：BLADE THERAPEUTICS INC

  公开号：WO2017156071A1

  公开（公告）日：2017-09-14

  The present technology relates to cyclic keto-amide compounds of general formulae I to XXXII, compositions and kits thereof as calpain modulators and methods useful for the treatment of various diseases or disorders such as fibrotic disease or cancer which are associated or mediated, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is also applicable to cyclic keto-amide compounds which inhibit myofibroblast differentiation.

  目前的技术涉及一般式I至XXXII的环状酮酰胺化合物，以及作为钙蛋白酶调节剂的组合物和试剂盒，以及用于治疗与钙蛋白酶（如CAPN1、CAPN2和/或CAPN9）相关或介导的各种疾病或紊乱的方法，如纤维化疾病或癌症。目前的技术还适用于抑制肌成纤维细胞分化的环状酮酰胺化合物。
• WO2008/97676
  申请人：——

  公开号：——

  公开（公告）日：——
• COMPOUNDS AND COMPOSITIONS AS CHANNEL ACTIVATING PROTEASE INHIBITORS
  申请人：Tully David C.

  公开号：US20100056756A1

  公开（公告）日：2010-03-04

  The invention provides compounds and pharmaceutical compositions thereof, which are useful for modulating channel activating proteases, and methods for, using such compounds to treat, ameliorate or prevent a condition associated with a channel activating protease, including but not limited to prostasin, PRSS22, TMPRSS11 (e.g., TMPRSS11B, TMPRSS11E), TMPRSS2, TMPRSS3, TMPRSS4 (MTSP-2), matriptase (MTSP-1), CAP2, CAP3, trypsin, cathepsin A, or neutrophil elastase.
• US8293915B2
  申请人：——

  公开号：US8293915B2

  公开（公告）日：2012-10-23