特波格雷 | 149979-74-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 特波格雷
• 英文名称: Terbogrel
• 英文别名: (E)-6-[3-[(N'-tert-butyl-N-cyanocarbamimidoyl)amino]phenyl]-6-pyridin-3-ylhex-5-enoic acid
• CAS: 149979-74-8
• 化学式: C₂₃H₂₇N₅O₂
• 分子量: 405.5
• InChiKey: XUTLOCQNGLJNSA-RGVLZGJSSA-N

物化性质

• 沸点：
  613.5±65.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  5

制备方法与用途

生物活性

Terbogrel 是一种可口服的 thromboxane A2 受体拮抗剂，和 thromboxane A2 synthase 的抑制剂，IC50 值均约为 10 nM。

靶点

IC50: apr 10 nM (thromboxane A2 receptor), appr 10 nM (thromboxane A2 synthase)

体外研究

Pretreatment of platelets with terbogrel 1 μM completely inhibits thrombin-induced thromboxane A2 formation (2±1 ng/mL) but does not result in any inhibition of platelet aggregation. Terbogrel (1 μM) completely inhibits U46619-induced platelet aggregation, and the IC ₅₀ value is 10 nM. Terbogrel inhibits both platelet aggregation and thromboxane A2 formation with an IC ₅₀ of about 10 nM. Terbogrel inhibits the thromboxane A2 synthase in human gel-filtered platelets with an IC ₅₀ value of 4.0 ± 0.5 nM. Terbogrel blocks the thromboxane A2/endoperoxide receptor on washed human platelets with an IC ₅₀ of 11 ± 6 nM (n = 2) and with an IC ₅₀ of 38 ± 1 nM (n = 15) in platelet-rich plasma. Terbogrel inhibits the collagen-induced platelet aggregation in human platelet-rich plasma and whole blood with an IC ₅₀ of 310 ± 18 nM (n = 8) and 52 ± 20 nM (n = 6), respectively.

体内研究

Terbogrel (0.1−3.0 mg/kg) demonstrates an impressive antithrombotic efficacy in rabbits. Terbogrel (10 mg/kg, po) is rapidly and well (90%) absorbed with a systemic availability of about 30% in rats.

反应信息

• 作为产物：
  描述：

  以45的产率得到特波格雷
  参考文献：
  名称：

  J. Med. Chem. 1999, 42, 1235-1249

  摘要：

  DOI：

文献信息

• Carboxylic acid amides, the preparation thereof, and their use as pharmaceutical compositions
  申请人：Boehringer Ingelheim Pharma GmbH & Co. KG

  公开号：US20040220169A1

  公开（公告）日：2004-11-04

  The present invention relates to new substituted carboxylic acid amides of general formula 1 wherein A, B and R 1 to R 5 are defined as in claim 1, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties. The compounds of the above general formula I as well as the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, and their stereoisomers have valuable pharmacological properties, particularly an antithrombotic activity and a factor Xa-inhibiting activity.

  本发明涉及一般式1的新取代羧酸酰胺，其中A、B和R1至R5如权利要求1中所定义，其互变异构体、对映异构体、非对映异构体、它们的混合物及其盐，特别是其与无机或有机酸或碱的生理上可接受的盐，具有有价值的性质。 上述一般式I的化合物以及其互变异构体、对映异构体、非对映异构体、它们的混合物及其盐，特别是其与无机或有机酸或碱的生理上可接受的盐，及其立体异构体具有有价值的药理学性质，特别是抗血栓活性和Xa因子抑制活性。
• [DE] NEUE CARBONSÄUREAMIDE, DEREN HERSTELLUNG UND DEREN VERWENDUNG ALS ARZNEIMITTEL<br/>[EN] NOVEL CARBOXAMIDES, THE PRODUCTION AND USE THEREOF AS MEDICAMENTS<br/>[FR] NOUVEAUX AMIDES D'ACIDE CARBOXYLIQUE, LEUR PRODUCTION ET LEUR UTILISATION EN TANT QUE MEDICAMENTS
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2004056784A1

  公开（公告）日：2004-07-08

  Gegenstand der vorliegenden Erfindung sind neue substituierte Carbonsäureamide der allgemeinen Formel (I), in der A, B und R1 bis R5 wie in Anspruch 1 definiert sind, deren Tautomere, deren Enantiomere, deren Diastereomere, deren Gemische und deren Salze, insbesondere deren physiologisch verträgliche Salze mit anorganischen oder organischen Säuren oder Basen, welche wertvolle Eigenschaften aufweisen. Die Verbindungen der obigen allgemeinen Formel (I) sowie deren Tautomere, deren Enantiomere, deren Diastereomere, deren Gemische und deren Salze, insbesondere deren physiologisch verträgliche Salze mit anorganischen oder organischen Säuren oder Basen, und deren Stereoisomere weisen wertvolle pharmakologische Eigenschaften auf, insbesondere eine antithrombotische Wirkung und eine Faktor Xa-inhibierende Wirkung.

  本发明涉及一种新的取代羧酰胺，其通式为(I)，其中A、B和R1至R5如权利要求1所定义，其互变异构体、对映异构体、非对映异构体、混合物和盐，特别是其与无机或有机酸或碱形成的生理相容盐，具有有价值的特性。上述通式(I)的化合物及其互变异构体、对映异构体、非对映异构体、混合物和盐，特别是其与无机或有机酸或碱形成的生理相容盐，以及其立体异构体具有有价值的药理特性，特别是抗血栓作用和Xa因子抑制作用。
• [DE] NEUE CARBONSÄUREAMIDE ALS FAKTOR XA-INHIBITOREN<br/>[EN] NOVEL CARBOXAMIDES FOR USE AS XA INHIBITORS<br/>[FR] NOUVEAUX CARBOXAMIDES COMME INHIBITEURS DU FACTEUR XA
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2005082895A1

  公开（公告）日：2005-09-09

  Gegenstand der vorliegenden Erfindung sind neue substituierte Carbonsäureamide der allgemeinen Formel (I), in der A, B und R1 bis R5 wie in Anspruch 1 definiert sind, deren Tautomere, deren Enantiomere, deren Diastereomere, deren Gemische und deren Salze, insbesondere deren physiologisch verträgliche Salze mit anorganischen oder organischen Säuren oder Basen, welche wertvolle Eigenschaften aufweisen. Die Verbindungen haben eine antithrombotische Wirkung uns sind Faktor Xa-Inhibitoren.

  The subject of the present invention is new substituted carboxylic acid amides of the general formula (I), in which A, B, and R1 to R5 are as defined in claim 1, their tautomers, their enantiomers, their diastereomers, their mixtures, and their salts, especially their physiologically acceptable salts with inorganic or organic acids or bases, which have valuable properties. The compounds have an antithrombotic effect and are Factor Xa inhibitors.
• New carboxylic acid amides, the preparation thereof and their use as medicaments
  申请人：Priepke Henning

  公开号：US20050203078A1

  公开（公告）日：2005-09-15

  The present invention relates to new substituted carboxylic acid amides of general formula wherein A, B and R 1 to R 5 are defined as in claim 1, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.

  本发明涉及一般式的新取代羧酸酰胺 其中A、B和R1至R5如权利要求1中定义，其互变异构体、对映体、非对映异构体、它们的混合物及其盐，特别是其与无机或有机酸或碱形成的生理上可接受的盐，具有有价值的性质。
• SUBSTITUTED PYRROLIDINE AMIDES, THE PRODUCTION THEREOF, AND THE USE THEREOF AS MEDICATIONS
  申请人：Gerlach Kai

  公开号：US20100099664A1

  公开（公告）日：2010-04-22

  The object of the present invention is novel substituted pyrrolidine amides of the general formula (I) in which D, L. E, G, J, M, L 1 , L 2 , R 4 , and R 5 are defined as in the specification, the tautomers, enantiomers, diastereomers, mixtures, and salts thereof, particularly physiologically tolerated salts with inorganic or organic acids or bases having valuable properties.

  本发明的对象是新颖的取代吡咯烷酰胺，其具有通式(I)，其中D、L、E、G、J、M、L1、L2、R4和R5如说明书所述定义，包括其互变异构体、对映异构体、非对映异构体、混合物以及盐，特别是具有宝贵性质的与无机或有机酸或碱的生理耐受盐。