2-cyano-5-(azidomethyl)thiophene | 368426-18-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 2-cyano-5-(azidomethyl)thiophene
• 英文别名: 5-(azidomethyl)thiophene-2-carbonitrile
• CAS: 368426-18-0
• 化学式: C₆H₄N₄S
• 分子量: 164.191
• InChiKey: MQICAJNDHSFIOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-cyano-5-(azidomethyl)thiophene 在 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 12.0h， 生成 (5-Cyano-thiophen-2-ylmethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Novel, Potent Non-Covalent Thrombin Inhibitors Incorporating P3-Lactam Scaffolds

  摘要：

  Evolution of P-1-argininal inhibitor prototypes led to a series of non-covalent P-3-7-membered lactam inhibitors 1a-w, featuring novel peptidomimetic units that probe each of the S-1, S-2, and S-3 specificity pockets of thrombin. Rigid P-1-arginine surrogates possessing a wide range of basicity (calcd pK(a)'ssimilar toneutral-14) were surveyed. The design, synthesis, and biological activity of these targets are presented. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00010-0
• 作为产物：
  描述：

  5-溴甲基噻吩-2-甲腈 在 sodium azide 、 四丁基氯化铵 作用下， 以 苯 为溶剂， 反应 1.0h， 生成 2-cyano-5-(azidomethyl)thiophene
  参考文献：
  名称：

  基于P1位置上的2,5-噻吩并嘧啶的有效且可口服生物利用的凝血酶抑制剂：N-羧甲基-d-二苯丙氨酰基-1-脯氨酰[（5-5-基-2-噻吩基）甲基]酰胺的发现。

  摘要：

  凝血酶是凝血中的关键酶，一直是抗血栓治疗的目标。口服活性凝血酶抑制剂可为静脉和动脉血栓形成提供有效和安全的预防。我们对高效的基于苯甲am的凝血酶抑制剂LB30812（3，K（i）= 3 pM）进行了优化，以提高口服生物利用度。在P1位置研究的各种芳基idine胺中，2,5-噻吩基idine胺有效替代了苯amam，而不会损害凝血酶的抑制作用和口服吸收。通常，在N末端位置进行磺酰胺和磺酰胺衍生化可提供高效的凝血酶抑制剂，但具有适度的口服吸收，而可吸收性强的N-氨基甲酸酯衍生物在S9馏分中的代谢稳定性有限。目前的工作最终是发现含有N-羧甲基和2,5-噻吩啶的化合物22，该化合物表现出最有利的抗凝血和抗血栓形成活性以及口服生物活性（K（i）= 15 pM; F =在大鼠，狗和猴子中分别为43％，42％和15％）。在大鼠和兔子的静脉血栓形成模型中，以重量计，该化合物显示出比低分子量肝素依诺肝素更有效

  DOI：

  10.1021/jm030025j

文献信息

• Non-covalent inhibitors of urokinase and blood vessel formation
  申请人：Corvas International, Inc.

  公开号：US20020037857A1

  公开（公告）日：2002-03-28

  Novel compounds having activity as non-covalent inhibitors of urokinase and having activity in reducing or inhibiting blood vessel formation are provided. These compounds have Pi a group having an amidino or guanidino moiety or derivative thereof. These compounds are useful in vitro for monitoring plasminogen activator levels and in vivo in treatment of conditions which are ameliorated by inhibition of or decreased activity of urokinase and in treating pathologic conditions wherein blood vessel formation is related to a pathologic condition.

  提供了一种具有作为尿激酶非共价抑制剂活性并在减少或抑制血管形成方面具有活性的新化合物。这些化合物具有Pi基团，其中含有一个酰胺基团或鸟胺基团或其衍生物。这些化合物在体外用于监测纤溶酶原激活剂水平，在体内用于治疗通过抑制尿激酶或降低其活性而得到改善的病症，以及用于治疗血管形成与病理病变相关的病理状况。
• Thrombin inhibitors having a lactam at P3
  申请人：Corvas International, Inc.

  公开号：US06541467B1

  公开（公告）日：2003-04-01

  The present invention provides compounds having a lactam ring at P3 and at P1 have a six-membered heterocyclic ring having two ring nitrogen ring atoms and the remainder of the ring atoms carbon atoms. These compounds have biological activity as active and potent inhibitors of thrombin. Their pharmaceutically acceptable salts, pharmaceutical compositions thereof and methods of using these compounds and pharmaceutical compositions comprising these compounds as therapeutic agents for treatment of disease states in mammals which are characterized by abnormal thrombosis are also described.

  本发明提供了在P3处具有内酰胺环，在P1处具有一个含有两个环氮原子和其余环原子为碳原子的六元杂环环的化合物。这些化合物作为活性和有效的凝血酶抑制剂具有生物活性。还描述了它们的药用可接受盐、包括这些化合物的药物组合物以及使用这些化合物和包含这些化合物的药物组合物作为治疗哺乳动物疾病状态的治疗剂的方法。
• Novel process for preparing 5-aminomethyl-2-thiophenecarbonitrile hcl by one-pot reaction
  申请人：——

  公开号：US20040116714A1

  公开（公告）日：2004-06-17

  The present invention provides a novel process for preparing a compound represented by the above formula 7, which is an important intermediate for an oral thrombin inhibitor, by one-pot reaction. In accordance with the present invention, the above intermediate for the thrombin inhibitor may be obtained in a high yield.

  本发明提供了一种新的制备上述7式化合物的方法，该化合物是口服凝血酶抑制剂的重要中间体，通过一锅法反应制备。根据本发明，可以高产得到凝血酶抑制剂的上述中间体。
• Non-covalent thrombin inhibitors featuring p 3 -heterocycles with P 1 -monocyclic arginine surrogates
  作者：John E Reiner、Daniel V Siev、Gian-Luca Araldi、Jingrong Jean Cui、Jonathan Z Ho、Komandla Malla Reddy、Lala Mamedova、Phong H Vu、Kuen-Shan S Lee、Nathaniel K Minami、Tony S Gibson、Susanne M Anderson、Annette E Bradbury、Thomas G Nolan、J.Edward Semple

  DOI：10.1016/s0960-894x(02)00129-4

  日期：2002.4

  Investigations on P-2-P-3-heterocyclic dipeptide surrogates directed towards identification of an orally bioavailable thrombin inhibitor led us to pursue novel classes of achiral, non-covalent P-1-arginine derivatives. The design. synthesis. and biological activity of inhibitors NC1-NC30 that feature three classes of monocyclic P-1-arginine surrogates will be disclosed: (1) (hetero)aromatic amidines, amines and hydrox amidines, (2) 2-aminopyrazines. and (3) 2-aminopyrimidines and 2-aminotetrahydropyrimidines. (C) 2002 Elsevier Science Ltd. All rights reserved.
• NOVEL PROCESS FOR PREPARING 5-AMINOMETHYL-2-THIOPHENECARBONITRILE. HCL BY ONE-POT REACTION
  申请人：LG Life Sciences Ltd.

  公开号：EP1383758A1

  公开（公告）日：2004-01-28