SCH 602539 | 618385-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: SCH 602539
• 英文别名: Carbamic acid, ((1R,3aR,4aR,6R,8aR,9S,9aS)-9-((1E)-2-(2,3'-bipyridin)-6'-ylethenyl)dodecahydro-1-methyl-3-oxonaphtho(2,3-C)furan-6-yl)-, ethyl ester；ethyl N-[(1R,3aR,4aR,6R,8aR,9S,9aS)-1-methyl-3-oxo-9-[(E)-2-(5-pyridin-2-ylpyridin-2-yl)ethenyl]-3a,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-benzo[f][2]benzofuran-6-yl]carbamate
• CAS: 618385-42-5
• 化学式: C₂₈H₃₃N₃O₄
• 分子量: 475.588
• InChiKey: IHWKYASJAJITBL-MSGZWQTISA-N

物化性质

• 沸点：
  684.0±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Vorapaxar Bromide Impurity 、 三正丁基2-吡啶基锌 在 钯 作用下， 生成 SCH 602539
  参考文献：
  名称：

  Discovery of a vorapaxar analog with increased aqueous solubility

  摘要：

  An analog of the thrombin receptor antagonist vorapaxar (SCH 530348) with increased aqueous solubility, compound 9c (SCH 602539), was discovered through incorporation of polar substituents on the pyridine ring of the himbacine-derived lead series. This analog retained the excellent potency, pharmacokinetic and safety properties of vorapaxar while increasing the aqueous solubility by 20-fold. Also presented are in vivo evaluations of this compound in a cynomolgus monkey platelet aggregation assay and in a Folts model of thrombosis in anesthetized monkeys. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.009

文献信息

• THROMBIN RECEPTOR ANTAGONISTS
  申请人：Chackalamannil Samuel

  公开号：US20070179187A1

  公开（公告）日：2007-08-02

  Heterocyclic-substituted tricyclics of the formula or a pharmaceutically acceptable salt thereof, wherein: the dotted line represents an optional single bond; represents an optional double bond, n is 0-2; Q is cycloalkyl, optionally substituted by R 13 and R 14 ; R 13 and R 14 are independently selected from (C 1 -C 6 )alkyl, (C 3 -C 8 )cycloalkyl, —OH, (C 1 -C 6 )alkoxy, R 27 -aryl(C 1 -C 6 )alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halogen and haloalkyl; or R 13 and R 14 together form a spirocyclic or a heterospirocyclic ring of 3-6 atoms, Het is a mono- or bi-cyclic optionally substituted heteroaryl group; and B is a bond, alkylene, or optionally substituted alkenylene or alkynylene, wherein the remaining substituents are as defined in the specification, are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds. Combination therapy with other cardiovascular agents is also claimed.

  公式为Heterocyclic-substituted tricyclics或其药学上可接受的盐，其中：虚线代表可选的单键；代表可选的双键，n为0-2；Q为环烷基，可选地由R13和R14取代；R13和R14独立地选择自（C1-C6）烷基，（C3-C8）环烷基，—OH，（C1-C6）烷氧基，R27-芳基（C1-C6）烷基，杂芳基，杂芳基烷基，杂环基，杂环基烷基，卤素和卤基；或R13和R14一起形成3-6个原子的螺环或杂螺环；Het是一个单环或双环的可选取代杂芳基基团；B为键，烷基，或可选取代的烯烃基或炔基，其中其余取代基如规范中所定义。还公开了含有这些化合物的制药组合物以及通过给予这些化合物治疗与血栓形成、动脉粥样硬化、再狭窄、高血压、心绞痛、心律失常、心力衰竭和癌症相关的疾病的方法。还声称与其他心血管药物的联合治疗。
• IMMEDIATE-RELEASE TABLET FORMULATIONS OF A THROMBIN RECEPTOR ANTAGONIST
  申请人：Gupta Rajan

  公开号：US20080031943A1

  公开（公告）日：2008-02-07

  Immediate-release formulations for oral administration of a thrombin receptor antagonist are provided. Certain formulations of higher API loading demonstrate sufficient moisture uptake after storage at stressed conditions to retard dissolution. The formulations of the present invention incorporate either lower API loading or elevated disintegrant-to-API ratios, found necessary to achieve disintegration rates required for immediate-release performance.

  本发明提供了口服血栓素受体拮抗剂的即时释放制剂。高API负荷的某些配方在受到应力条件储存后表现出足够的吸湿性，以延缓溶解。本发明的配方采用较低的API负荷或升高的分散剂/ API比例，以实现所需的分散速率，以达到即时释放性能。
• Tricyclic thrombin receptor antagonists
  申请人：Schering Corporation

  公开号：EP1860106A1

  公开（公告）日：2007-11-28

  Claimed is a process for the manufacture of compounds of the following general formula (II): wherein Rx represent a group selected from COOCH2CH3, SO2CH3, CONHCH3, and COCH3, comprising the step of reacting the compound of the following formula (α-13) with a compound of the general formula Rx-X, wherein X represents a leaving group and wherein Rx is as defined above. Also claimed is a process for the manufacture of pharmaceutical compositions comprising compounds of the following formula (II) or pharmaceutically acceptable salts or solvates thereof.

  所要求的是一种制造下列通式(II)化合物的工艺： 其中 Rx 代表选自 COOCH2CH3、SO2CH3、CONHCH3 和 COCH3 的基团、 包括使下式（α-13）化合物反应的步骤 与通式 Rx-X 的化合物反应，其中 X 代表离去基团，Rx 如上所定义。 还要求一种制造药物组合物的工艺，该组合物包含下式(Ⅱ)化合物或其药学上可接受的盐或溶液。
• Immediate-release tablet formulations of a thrombin receptor antagonist
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2491922B1

  公开（公告）日：2017-01-04
• Methods for preventing and/or treating a cell proliferative disorder
  申请人：Liu Suxing

  公开号：US20070219154A1

  公开（公告）日：2007-09-20

  The present invention relates to methods for preventing and/or treating the growth and/or metastasis of a cell proliferative disorder. In particular, the methods include use of a protease activated receptor-1 (PAR-1) inhibitor.