4-((S)-4-carboxy-2-{[6-((S)-3-methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}butyryl)piperazine-1-carboxylic acid butyl ester

• 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: 4-((S)-4-carboxy-2-{[6-((S)-3-methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}butyryl)piperazine-1-carboxylic acid butyl ester
• 英文别名: (4S)-5-(4-butoxycarbonylpiperazin-1-yl)-4-[[6-[(3S)-3-methoxypyrrolidin-1-yl]-2-phenylpyrimidine-4-carbonyl]amino]-5-oxopentanoic acid
• 化学式: C₃₀H₄₀N₆O₇
• 分子量: 596.684
• InChiKey: UQSSLAGCQOGIPL-GOTSBHOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  43
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  155
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  氯甲酸丁酯 在 palladium on activated charcoal 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 4-((S)-4-carboxy-2-{[6-((S)-3-methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}butyryl)piperazine-1-carboxylic acid butyl ester
  参考文献：
  名称：

  Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable and selective P2Y12 antagonists for inhibition of platelet aggregation

  摘要：

  2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y12 antagonists. Optimization of the carbon-linked or nitrogen-linked substituent at the 6-position of the pyrimidine ring provided compounds with excellent ex vivo potency in the platelet aggregation assay in human plasma. Compound 23u met the objectives for activity, selectivity and ADMET properties.

  DOI：

  10.1016/j.bmcl.2014.06.070

文献信息

• [EN] PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS D'ACIDE PHOSPHONIQUE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DU RÉCEPTEUR P2Y12
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2009069100A1

  公开（公告）日：2009-06-04

  The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

  这项发明涉及含有膦酸基团的2-苯基嘧啶衍生物，以及它们作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏-、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的疾病或状况中的使用，包括人类和其他哺乳动物中的血栓形成。（I）。
• PHOSPHONIC ACID DERIVATES AD THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
  申请人：Caroff Eva

  公开号：US20100261678A1

  公开（公告）日：2010-10-14

  The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y 12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).

  本发明涉及含有膦酸基团的2-苯基嘧啶衍生物及其作为P2Y12受体拮抗剂在治疗和/或预防外周血管、内脏、肝脏和肾脏血管、心血管和脑血管疾病或与血小板聚集有关的病症，包括人类和其他哺乳动物的血栓形成中的应用。(I)。
• US8518912B2
  申请人：——

  公开号：US8518912B2

  公开（公告）日：2013-08-27
• Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable and selective P2Y12 antagonists for inhibition of platelet aggregation
  作者：Eva Caroff、Emmanuel Meyer、Alexander Treiber、Kurt Hilpert、Markus A. Riederer

  DOI：10.1016/j.bmcl.2014.06.070

  日期：2014.9

  2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y12 antagonists. Optimization of the carbon-linked or nitrogen-linked substituent at the 6-position of the pyrimidine ring provided compounds with excellent ex vivo potency in the platelet aggregation assay in human plasma. Compound 23u met the objectives for activity, selectivity and ADMET properties.