3-[1-(5-phenylethynyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzamidine hydrochloride

• 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]-benzamidine hydrochloride
• 英文别名: 3-[1-[5-(2-phenylethynyl)pyridine-3-carbonyl]piperidin-4-yl]benzenecarboximidamide;hydrochloride
• 化学式: C₂₆H₂₄N₄O*ClH
• 分子量: 444.964
• InChiKey: GSNLUNOXVQEZAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.21
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  83.1
• 氢给体数：
  3
• 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]-benzamidine hydrochloride 在 钯 氢气 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以to give the title compound as a colourless oil (150 mg)的产率得到3-[1-(5-Phenylethyl-pyridine-3-carbonyl)-piperidin-4-yl]-benzamidine hydrochloride
  参考文献：
  名称：

  1-aroyl-piperidinyl benzamidines

  摘要：

  本发明涉及以下公式的化合物，其抑制因子Xa或胰蛋白酶，以及含有这些化合物的制药组合物，以及利用这些化合物治疗因子Xa或胰蛋白酶抑制剂治疗可以改善的病患的用途。

  公开号：

  US07947684B2
• 作为产物：
  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

文献信息

• 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
• US7947684B2
  申请人：——

  公开号：US7947684B2

  公开（公告）日：2011-05-24
• [EN] 1-AROYL-PIPERIDINYL BENZAMIDINES<br/>[FR] 1-AROYLE-PIPERIDINYLE BENZAMIDINES
  申请人：AVENTIS PHARM PROD INC

  公开号：WO2001081310A1

  公开（公告）日：2001-11-01

  This invention relates to compounds of formula (I) 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.
• Structure based design of 4-(3-aminomethylphenyl)piperidinyl-1-amides: novel, potent, selective, and orally bioavailable inhibitors of βII tryptase
  作者：Julian Levell、Peter Astles、Paul Eastwood、Jennifer Cairns、Olivier Houille、Suzanne Aldous、Gregory Merriman、Brian Whiteley、James Pribish、Mark Czekaj、Guyan Liang、Sebastien Maignan、Jean-Pierre Guilloteau、Alain Dupuy、Jane Davidson、Trevor Harrison、Andrew Morley、Simon Watson、Garry Fenton、Clive McCarthy、Joseph Romano、Rose Mathew、Darren Engers、Michael Gardyan、Keith Sides、Jennifer Kwong、Joseph Tsay、Sam Rebello、Liduo Shen、Jie Wang、Yongyi Luo、Odessa Giardino、Heng-Keang Lim、Keith Smith、Henry Pauls

  DOI：10.1016/j.bmc.2005.02.014

  日期：2005.4

  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.