3-[1-(5-phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzonitrile | 851961-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-[1-(5-phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzonitrile
• 英文别名: 3-[-(5-Phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzonitrile；3-[1-[5-(2-phenylethynyl)pyridine-3-carbonyl]piperidin-4-yl]benzonitrile
• CAS: 851961-36-9
• 化学式: C₂₆H₂₁N₃O
• 分子量: 391.472
• InChiKey: SBLPCQRAYNSXLK-UHFFFAOYSA-N

物化性质

• 沸点：
  627.2±55.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  57
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-[1-(5-phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzonitrile 在 盐酸 、 氨 作用下， 以 甲醇 为溶剂， 反应 66.0h， 生成 3-[1-(5-phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzamidine hydrochloride
  参考文献：
  名称：

  Structure based design of 4-(3-aminomethylphenyl)piperidinyl-1-amides: novel, potent, selective, and orally bioavailable inhibitors of βII tryptase

  摘要：

  Tryptase is a serine protease found almost exclusively in mast cells. It has trypsin-like specificity, favoring cleavage of substrates with an arginine (or lysine) at the P1 position, and has optimal catalytic activity at neutral pH. Current evidence suggests tryptase beta is the most important form released during mast cell activation in allergic diseases. It is shown to have numerous pro-inflammatory cellular activities in vitro, and in animal models tryptase provokes broncho-constriction and induces a cellular inflammatory infiltrate characteristic of human asthma. Screening of in-house inhibitors of factor Xa (a closely related serine protease) identified beta-amidoester benzamidines as potent inhibitors of recombinant human betaII tryptase. X-ray structure driven template modification and exchange of the benzamidine to optimize potency and pharmacokinetic properties gave selective, potent and orally bioavailable 4-(3-aminomethyl phenyl)piperidinyl-1-amides.

  DOI：

  10.1016/j.bmc.2005.02.014
• 作为产物：
  描述：

  benzyl 4-(3-cyanophenyl)-5,6-dihydropyridine-1(2H)-carboxylate 在 palladium on activated charcoal 氢气 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 3-[1-(5-phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzonitrile
  参考文献：
  名称：

  Structure based design of 4-(3-aminomethylphenyl)piperidinyl-1-amides: novel, potent, selective, and orally bioavailable inhibitors of βII tryptase

  摘要：

  Tryptase is a serine protease found almost exclusively in mast cells. It has trypsin-like specificity, favoring cleavage of substrates with an arginine (or lysine) at the P1 position, and has optimal catalytic activity at neutral pH. Current evidence suggests tryptase beta is the most important form released during mast cell activation in allergic diseases. It is shown to have numerous pro-inflammatory cellular activities in vitro, and in animal models tryptase provokes broncho-constriction and induces a cellular inflammatory infiltrate characteristic of human asthma. Screening of in-house inhibitors of factor Xa (a closely related serine protease) identified beta-amidoester benzamidines as potent inhibitors of recombinant human betaII tryptase. X-ray structure driven template modification and exchange of the benzamidine to optimize potency and pharmacokinetic properties gave selective, potent and orally bioavailable 4-(3-aminomethyl phenyl)piperidinyl-1-amides.

  DOI：

  10.1016/j.bmc.2005.02.014

文献信息

• Chemical compounds
  申请人：——

  公开号：US20030187020A1

  公开（公告）日：2003-10-02

  Provided herein are novel and useful compounds having a tryptase inhibition activity, pharmaceutical compositions comprising such compounds, and methods treating subjects suffering from a condition, disease, or disorder that can be ameliorated by the administration of an inhibitor of tryptase, e.g., asthma and inflammatory diseases, to name only a few.

  本文提供了具有胰蛋白酶抑制活性的新颖和有用化合物，包括含有这些化合物的药物组合物，以及治疗患有可以通过给予胰蛋白酶抑制剂（例如哮喘和炎症性疾病等）而得到改善的疾病、疾病或紊乱的方法。
• 1-aroyl-piperidinyl benzamidines
  申请人：——

  公开号：US20020045613A1

  公开（公告）日：2002-04-18

  This invention relates to compounds of formula 1 which inhibit Factor Xa or tryptase, to pharmaceutical compositions containing the compounds, and to the use of the compounds for the treatment of patients suffering from conditions which can be ameliorated by the administration of an inhibitor of Factor Xa or tryptase.

  该发明涉及一种公式1的化合物，其能够抑制Xa因子或胰蛋白酶，以及含有这些化合物的药物组合物，以及利用这些化合物治疗患有可以通过给予Xa因子或胰蛋白酶抑制剂而得到改善的病患的方法。
• [EN] ARYLMETHYLAMINE DERIVATIVES FOR USE AS TRYPTASE INHIBITORS<br/>[FR] DERIVES D'ARYLMETHYLAMINE UTILISES COMME INHIBITEURS DE LA TRYPTASE
  申请人：AVENTIS PHARM PROD INC

  公开号：WO2001090101A1

  公开（公告）日：2001-11-29

  Provided herein are compounds of formula (I) wherein R1-4, n and Ar are as defined in claim 1, and their pharmaceutical compositions. These compounds are tryptase inhibitors and may be used in the treatment of e.g. asthma and inflammatory diseases.

  本发明提供了式(I)的化合物，其中R1-4、n和Ar如权利要求1所定义，以及它们的药物组成物。这些化合物是胰蛋白酶抑制剂，可用于治疗哮喘和炎症性疾病等疾病。
• 1-Aroyl-piperidinyl benzamidines
  申请人：AVENTIS PHARMACEUTICALS INC

  公开号：US20040220171A1

  公开（公告）日：2004-11-04

  This invention relates to compounds of formula 1 which inhibit Factor Xa or tryptase, to pharmaceutical compositions containing the compounds, and to the use of the compounds for the treatment of patients suffering from conditions which can be ameliorated by the administration of an inhibitor of Factor Xa or tryptase.

  本发明涉及式1化合物，其抑制因子Xa或胰蛋白酶，以及含有该化合物的药物组合物，以及使用该化合物治疗患有可通过给予因子Xa或胰蛋白酶抑制剂治疗的疾病的患者的用途。
• 1-AROYL-PIPERIDINYL BENZAMIDINES
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP1278732A1

  公开（公告）日：2003-01-29