5-(氨基甲基)噻吩-3-甲腈 | 232280-88-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 5-(氨基甲基)噻吩-3-甲腈
• 英文名称: 2-aminomethyl-4-cyanothiophene
• 英文别名: 5-(aminomethyl)-3-thiophenecarbonitrile；5-aminomethyl-3-cyanothiophene；5-(Aminomethyl)thiophene-3-carbonitrile
• CAS: 232280-88-5
• 化学式: C₆H₆N₂S
• 分子量: 138.193
• InChiKey: OSDGTEZAPBYUQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  78
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-(氨基甲基)噻吩-3-甲腈 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 0.75h， 生成 N-[[(2R)-1-[4-(butylamino)-6-[(4-cyanothiophen-2-yl)methylamino]-1,3,5-triazin-2-yl]pyrrolidin-2-yl]methyl]-4-propylbenzenesulfonamide
  参考文献：
  名称：

  Discovery of Highly Potent and Selective Small Molecule ADAMTS-5 Inhibitors That Inhibit Human Cartilage Degradation via Encoded Library Technology (ELT)

  摘要：

  The metalloprotease ADAMTS-5 is considered a potential target for the treatment of osteoarthritis. To identify selective inhibitors of ADAMTS-5, we employed encoded library technology (ELT), which enables affinity selection of small molecule binders from complex mixtures by DNA tagging. Selection of ADAMTS-5 against a four-billion member ELT library led to a novel inhibitor scaffold not containing a classical zinc-binding functionality. One exemplar, (R)-N-((1-(4-(but-3-en-1-ylamino)-6-(((2-(thiophen-2-yl)thiazol-4-yl)methyl)amino)-1,3,5-triazin-2-yl)pyrrolidin-2-yl)methyl)-4-propylbenzenesulfonamide (8), inhibited ADAMTS-5 with IC50 = 30 nM, showing >50-fold selectivity against ADAMTS-4 and >1000-fold selectivity against ADAMTS-1, ADAMTS-13, MMP-13, and TACE. Extensive SAR studies showed that potency and physicochemical properties of the scaffold could be further improved. Furthermore, in a human osteoarthritis cartilage explant study, compounds 8 and 15f inhibited aggrecanase-mediated (374)ARGS neoepitope release from aggrecan and glycosaminoglycan in response to IL-1 beta/OSM stimulation. This study provides the first small molecule evidence for the critical role of ADAMTS-5 in human cartilage degradation.

  DOI：

  10.1021/jm300449x
• 作为产物：
  描述：

  5-(hydroxymethyl)thiophene-3-carbonitrile 在 叠氮磷酸二苯酯 、 palladium 10% on activated carbon 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 5-(氨基甲基)噻吩-3-甲腈
  参考文献：
  名称：

  [EN] PHARMACEUTICAL COMPOUNDS FOR THE TREATMENT OF COMPLEMENT MEDIATED DISORDERS
  [FR] COMPOSÉS PHARMACEUTIQUES POUR LE TRAITEMENT DE TROUBLES MÉDIÉS PAR LE COMPLÉMENT

  摘要：

  这份披露提供了用于治疗医学疾病的药物化合物，例如包括补体介导的疾病在内的补体Cl-介导的疾病。

  公开号：

  WO2020198062A1

文献信息

• [EN] PHARMACEUTICAL COMPOUNDS FOR THE TREATMENT OF COMPLEMENT MEDIATED DISORDERS<br/>[FR] COMPOSÉS PHARMACEUTIQUES POUR LE TRAITEMENT DE TROUBLES MÉDIÉS PAR LE COMPLÉMENT
  申请人：ACHILLION PHARMACEUTICALS INC

  公开号：WO2020198062A1

  公开（公告）日：2020-10-01

  This disclosure provides pharmaceutical compounds to treat medical disorders, such as complement-mediated disorders, including complement Cl -mediated disorders.

  这份披露提供了用于治疗医学疾病的药物化合物，例如包括补体介导的疾病在内的补体Cl-介导的疾病。
• Integrin receptors antagonists
  申请人：Abbott GmbH & Co. KG

  公开号：US07105508B1

  公开（公告）日：2006-09-12

  The invention relates to novel compounds which bind to integrin receptors, and to the preparation thereof and the use thereof as drugs.

  这项发明涉及结合到整合素受体的新化合物，以及其制备和作为药物的用途。
• Thrombin inhibitors
  申请人：Abbott GmbH & Co., KG

  公开号：US06740647B1

  公开（公告）日：2004-05-25

  Novel five-membered heterocyclic amidines, their preparation and use as competitive inhibitors of trypsin-like serine proteases, especially thrombin and kininogenases such as kallikrein. Pharmaceutical compositions which contain the compounds as active ingredients, and use of the compounds as thrombin inhibitors, anticoagulants and antiinflammatory agents.

  新型五元杂环胺基化物，其制备和用作胰蛋白酶样丝氨酸蛋白酶的竞争性抑制剂，特别是血栓素和激肽原酶如激肽原酶的抑制剂。含有这些化合物作为活性成分的药物组合物，以及将这些化合物用作血栓素抑制剂、抗凝剂和抗炎药剂。
• [EN] THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE THROMBINE
  申请人：LG CHEMICAL LTD

  公开号：WO2000039124A1

  公开（公告）日：2000-07-06

  The present invention relates to thrombin inhibitors of formula (I), wherein A, B, C, D, E, F and n have the meaning given in the description, that are useful as anticoagulants. In particular, this invention relates to peptide derivatives having high antithrombotic activity and high oral bioavailability.

  本发明涉及式(I)的凝血酶抑制剂，其中A、B、C、D、E、F和n具有描述中给定的含义，可用作抗凝剂。特别是，本发明涉及具有高抗血栓活性和高口服生物利用度的肽衍生物。
• Low-molecular serine proteases inhibitors comprising polyhydroxy-alkyl and polyhydroxy-cycloalkyl radicals
  申请人：——

  公开号：US20040048815A1

  公开（公告）日：2004-03-11

  The invention relates to novel amidines and quanidines, the production and use thereof and the use thereof as trypsine-type serine protease competitive inhibitors, especially thrombine and compliment proteases CIs and C1r. The invention also relates to pharmaceutical compositions which contain said compounds as active ingredients, in addition to the use of the compounds as thrombine inhibitors, anticoagulants, compliment inhibitors and anti-inflammatory agents. The novel compositions are characterised by the linkage of a serine protease inhibitor having amidine or quanidine functions with an alkyl radical having two or more hydroxyl functions, whereby said alkyl radical is derived from sugar derivates.Several sugar structural components or components derived from sugar can therefore be linked to each other. Said principle of linking sugar derivates enables oral active compounds to be obtained.

  本发明涉及新型的氨基脲和胍类化合物，其生产和使用以及作为胰蛋白酶类丝氨酸蛋白酶竞争性抑制剂的用途，特别是作为凝血酶和补体蛋白酶CIs和C1r的抑制剂。本发明还涉及含有所述化合物作为活性成分的制药组合物，以及将该化合物用作凝血酶抑制剂、抗凝剂、补体抑制剂和抗炎剂的用途。新型组合物的特点是将具有氨基脲或胍类功能的丝氨酸蛋白酶抑制剂与具有两个或更多羟基功能的烷基基团连接起来，所述烷基基团源自糖衍生物。因此，几种糖结构组分或从糖中衍生的组分可以相互连接。这种将糖衍生物连接起来的原理使得可以获得口服活性化合物。