3-(N-4-cyanobenzoyl)amino-2,2-dimethyl-4-hexenoic acid | 208397-06-2

• 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: 3-(N-4-cyanobenzoyl)amino-2,2-dimethyl-4-hexenoic acid
• CAS: 208397-06-2
• 化学式: C₁₆H₁₈N₂O₃
• 分子量: 286.331
• InChiKey: HQICGTGVVOMKSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  21.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  90.19
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-(N-4-cyanobenzoyl)amino-2,2-dimethyl-4-hexenoic acid 在 硫化氢 、 ammonium acetate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 、 碘甲烷 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 {1-[3-(4-Carbamimidoyl-benzoylamino)-2,2-dimethyl-hex-5-enoyl]-piperidin-4-yl}-acetic acid methyl ester
  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：

  4-(2-propenyl)-3,3-dimethyl-2-azetidinone 在 氢氧化钾 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 89.0h， 生成 3-(N-4-cyanobenzoyl)amino-2,2-dimethyl-4-hexenoic 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