Methyl N-(3-(4-cyanobenzyloxy)benzoyl)-DL-3-amino-4,4,4-trifluorobutyrate | 183014-66-6

• 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: Methyl N-(3-(4-cyanobenzyloxy)benzoyl)-DL-3-amino-4,4,4-trifluorobutyrate
• 英文别名: Methyl 3-[[3-[(4-cyanophenyl)methoxy]benzoyl]amino]-4,4,4-trifluorobutanoate
• CAS: 183014-66-6
• 化学式: C₂₀H₁₇F₃N₂O₄
• 分子量: 406.361
• InChiKey: HEUOTCOJHYIDLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  88.4
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  甲醇 、 Methyl N-(3-(4-cyanobenzyloxy)benzoyl)-DL-3-amino-4,4,4-trifluorobutyrate 在 盐酸 、 氨 作用下， 生成
  参考文献：
  名称：

  Design, synthesis, and in vitro activities of benzamide-core glycoprotein IIb/IIIa antagonists: 2,3-Diaminopropionic acid derivatives as surrogates of aspartic acid

  摘要：

  In an effort to discover novel nonpeptide glycoprotein IIb/IIIa (GPIIb/lIIa, alpha(IIb)/beta 3) inhibitors, we investigated RGD mimetics featuring a 3-substituted benzoic acid as the core, benzamidine as the basic moiety, and a series of beta- and alpha-substituted beta-alanine derivatives as aspartic acid surrogates. It was found that the use of beta-methyl beta-alanine slightly improved the anti-aggregant potency in human platelet-rich plasma over the unsubstituted beta-alanine compound, while alpha-substitution with a trifluoromethyl group resulted in considerable loss in activity. Significant enhancement (up to 100-fold) in potency was obtained when the beta-alanine was replaced with N-2-substituted L-2,3-diaminopropionic acid derivatives. Among the three types of cc-substituents (carbamate, amide, and sulfonamide) investigated, no apparent preference was observed with respect to in vitro potency. However, alkyl groups were more favorable than arylalkyl groups (Cbz) in the carbamate analogues. We also investigated piperidine, piperazine, and N-formamidinopiperidine as replacements for the benzamidine moiety. The former two replacements led to a drop in potency while the latter replacement resulted in maintenance of activity as compared with the corresponding benzamidine analogue. (C) 1997 The DuPont Merck Pharmaceutical Company. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00013-8
• 作为产物：
  描述：

  methyl 3-((4-cyanobenzyl)oxy)benzoate 在 lithium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 Methyl N-(3-(4-cyanobenzyloxy)benzoyl)-DL-3-amino-4,4,4-trifluorobutyrate
  参考文献：
  名称：

  Design, synthesis, and in vitro activities of benzamide-core glycoprotein IIb/IIIa antagonists: 2,3-Diaminopropionic acid derivatives as surrogates of aspartic acid

  摘要：

  In an effort to discover novel nonpeptide glycoprotein IIb/IIIa (GPIIb/lIIa, alpha(IIb)/beta 3) inhibitors, we investigated RGD mimetics featuring a 3-substituted benzoic acid as the core, benzamidine as the basic moiety, and a series of beta- and alpha-substituted beta-alanine derivatives as aspartic acid surrogates. It was found that the use of beta-methyl beta-alanine slightly improved the anti-aggregant potency in human platelet-rich plasma over the unsubstituted beta-alanine compound, while alpha-substitution with a trifluoromethyl group resulted in considerable loss in activity. Significant enhancement (up to 100-fold) in potency was obtained when the beta-alanine was replaced with N-2-substituted L-2,3-diaminopropionic acid derivatives. Among the three types of cc-substituents (carbamate, amide, and sulfonamide) investigated, no apparent preference was observed with respect to in vitro potency. However, alkyl groups were more favorable than arylalkyl groups (Cbz) in the carbamate analogues. We also investigated piperidine, piperazine, and N-formamidinopiperidine as replacements for the benzamidine moiety. The former two replacements led to a drop in potency while the latter replacement resulted in maintenance of activity as compared with the corresponding benzamidine analogue. (C) 1997 The DuPont Merck Pharmaceutical Company. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00013-8

文献信息

• Aromatic compounds containing basic and acidic termini useful as
  申请人：The Dupont Merck Pharmaceutical Company

  公开号：US05563158A1

  公开（公告）日：1996-10-08

  This invention relates to novel compounds containing basic and acidic termini, pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.

  这项发明涉及含有碱性和酸性末端的新化合物，包含这些化合物的药物组合物，制备这些化合物的方法，以及使用这些化合物的方法，单独或与其他治疗剂结合，用于抑制血小板聚集，作为溶栓剂，和/或用于治疗血栓栓塞性疾病。
• Design, synthesis, and in vitro activities of benzamide-core glycoprotein IIb/IIIa antagonists: 2,3-Diaminopropionic acid derivatives as surrogates of aspartic acid
  作者：Chu-Biao Xue、John Roderick、Sharon Jackson、Maria Rafalski、Arlene Rockwell、Shaker Mousa、Richard E. Olson、William F. DeGrado

  DOI：10.1016/s0968-0896(97)00013-8

  日期：1997.4

  In an effort to discover novel nonpeptide glycoprotein IIb/IIIa (GPIIb/lIIa, alpha(IIb)/beta 3) inhibitors, we investigated RGD mimetics featuring a 3-substituted benzoic acid as the core, benzamidine as the basic moiety, and a series of beta- and alpha-substituted beta-alanine derivatives as aspartic acid surrogates. It was found that the use of beta-methyl beta-alanine slightly improved the anti-aggregant potency in human platelet-rich plasma over the unsubstituted beta-alanine compound, while alpha-substitution with a trifluoromethyl group resulted in considerable loss in activity. Significant enhancement (up to 100-fold) in potency was obtained when the beta-alanine was replaced with N-2-substituted L-2,3-diaminopropionic acid derivatives. Among the three types of cc-substituents (carbamate, amide, and sulfonamide) investigated, no apparent preference was observed with respect to in vitro potency. However, alkyl groups were more favorable than arylalkyl groups (Cbz) in the carbamate analogues. We also investigated piperidine, piperazine, and N-formamidinopiperidine as replacements for the benzamidine moiety. The former two replacements led to a drop in potency while the latter replacement resulted in maintenance of activity as compared with the corresponding benzamidine analogue. (C) 1997 The DuPont Merck Pharmaceutical Company. Published by Elsevier Science Ltd.