N-4-cyanobenzoyl-beta-phenethyl-alpha,alpha-dimethyl-beta-alanine | 180181-50-4

• 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: N-4-cyanobenzoyl-beta-phenethyl-alpha,alpha-dimethyl-beta-alanine
• 英文别名: 3-[(4-cyanobenzoyl)amino]-2,2-dimethyl-5-phenylpentanoic acid
• CAS: 180181-50-4
• 化学式: C₂₁H₂₂N₂O₃
• 分子量: 350.417
• InChiKey: MUWQLVLLWTYRSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-4-cyanobenzoyl-beta-phenethyl-alpha,alpha-dimethyl-beta-alanine 在 palladium dihydroxide 硫化氢 、 ammonium acetate 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 碘甲烷 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 18.25h， 生成 {1-[3-(4-Carbamimidoyl-benzoylamino)-2,2-dimethyl-5-phenyl-pentanoyl]-piperidin-4-yl}-acetic acid
  参考文献：
  名称：

  GPIIb/IIIa Integrin Antagonists with the New Conformational Restriction Unit, Trisubstituted β-Amino Acid Derivatives, and a Substituted Benzamidine Structure

  摘要：

  Ethyl N- [3 -(2-fluoro-4-(thiazolidin-3-yl(imino)methyl)benzoyl)amino-2,2-dimethylpentanoyl]piperidine-4-acetate 40 (NSL-96184:) is a highly potent and orally active fibrinogen receptor antagonist, which is characterized by the presence of the trisubstituted beta-amino acid residue, 3 -ethyl-2,2-dimethyl-beta-alanine. This compound was developed on the basis of the SAR study of N-[3-(N-4-amidinobenzoyl)amino-2,2-dimethyl-3-phenylpropionyl]piperidine-4-acetic acid 1 (NSL-95301) with the derivatization focused on the central trisubstituted beta-amino acid unit as well as the basic amidinobenzoyl unit, and the esterification of the carboxyl group for prodrug composition, Compound 1, which was report;ed in our previous study, was discovered by the application of combinatorial chemistry. The molecular modeling study suggests that the trisubstituted beta-amino acid unit is responsible for fixing the molecule to its active conformation. Compound 40 showed an excellent profile in the in vitro and in vivo studies for its human platelet aggregation inhibitory activity and oral availability in guinea pigs. This oral availability largely depends on the modification of the amidino group with a cyclic secondary amine, i.e., thiazolidine in 40. In in vivo studies, the onset of the antiplatelet action of 40 is very fast after oral administration, whereas its duration of action is relatively short. These results suggest that 40 has an excellent therapeutic potential, especially for antithrombotic treatment in the acute phase. 3-Substituted-2,2-dimethyl-beta-amino acid residues would serve as new and useful linear templates to restrict the conformational flexibility of peptidomimetics.

  DOI：

  10.1021/jm980126v
• 作为产物：
  描述：

  3,3-dimethyl-4-(2'-phenylethyl)azetidin-2-one 在 盐酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 66.0h， 生成 N-4-cyanobenzoyl-beta-phenethyl-alpha,alpha-dimethyl-beta-alanine
  参考文献：
  名称：

  N- [2,2-二甲基-3-（N-（4-氰基苯甲酰基）氨基）壬酰基] -L-苯丙氨酸乙酯作为糜蛋白酶样丝氨酸蛋白酶的稳定酯型抑制剂：有效抑制α的结构要求-胰凝乳蛋白酶。

  摘要：

  我们介绍了一种新的强效抑制剂，N- [2,2-二甲基-3-（N-（4-氰基苯甲酰基）氨基）壬酰基] -L-苯丙氨酸乙酯（3），它优先抑制属于胰凝乳蛋白酶超家族的丝氨酸蛋白酶。 。该抑制剂尽管由稳定的乙酯结构组成，但通过充当酰化剂，对牛α-胰凝乳蛋白酶，人组织蛋白酶G和猪弹性蛋白酶显示出强大的抑制活性。计算出的针对α-胰凝乳蛋白酶的失活速率常数（运动）和酶抑制剂解离常数（Ki）分别为0.0028 s-1和0.0045 microM（运动/ Ki = 630 000 M-1 s-1）。这些动力学参数表明该抑制剂是有史以来最强大的α-胰凝乳蛋白酶灭活剂之一。根据3的类似物的结构-活性关系（SAR）和结构-稳定性关系研究，在分子的三个部分（即4-氰基苯基），β-氨基酸残基处的β-取代基上进行了修饰以及酯结构，我们认为3的强抑制活性归因于以下结构特征：（1）强制特定酰基酶形成的乙酯，（2）β位置的正

  DOI：

  10.1021/jm980562h

文献信息

• Fibrinogen receptor antagonist and pharmaceutical compositions
  申请人：Nippon Steel Corporation

  公开号：US05866592A1

  公开（公告）日：1999-02-02

  Compounds of the following general formula (I) and pharmaceutically acceptable salts thereof.

  以下一般式(I)的化合物及其药学上可接受的盐。
• Symmetrical anhydride-type serine protease inhibitors: Structure-activity relationship studies of human chymase inhibitors
  作者：Kiyoko Iijima、Jun Katada、Yoshio Hayashi

  DOI：10.1016/s0960-894x(99)00012-8

  日期：1999.2

  We prepared a potent and relatively selective human chymase inhibitor 9 (-), based on the study of SAR of a symmetrical anhydride-type serine protease inhibitor 1. Kinetic studies suggested that 9 (-) reacts with the Ser residue at the active site of the enzyme, forming a stable acyl enzyme complex. We also showed the importance of the tri-substituted beta-amino acid structure for the potent anti-enzymatic activity, (C) 1999 Elsevier Science Ltd. All rights reserved.
• FIBRINOGEN RECEPTOR ANTAGONISTS HAVING SUBSTITUTED (b)-AMINO ACID RESIDUES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
  申请人：Nippon Steel Corporation

  公开号：EP0800516B1

  公开（公告）日：2001-09-19
• JPH1149739A
  申请人：——

  公开号：JPH1149739A

  公开（公告）日：1999-02-23
• US5866592A
  申请人：——

  公开号：US5866592A

  公开（公告）日：1999-02-02