C-[1-(2-Chloro-pyrimidin-4-yl)-piperidin-4-yl]-methylamine | 876144-87-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: C-[1-(2-Chloro-pyrimidin-4-yl)-piperidin-4-yl]-methylamine
• 英文别名: (1-(2-Chloropyrimidin-4-yl)piperidin-4-yl)methanamine；[1-(2-chloropyrimidin-4-yl)piperidin-4-yl]methanamine
• CAS: 876144-87-5
• 化学式: C₁₀H₁₅ClN₄
• 分子量: 226.709
• InChiKey: VFMAOEDODJWCHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  C-[1-(2-Chloro-pyrimidin-4-yl)-piperidin-4-yl]-methylamine 、 3-[2-[2,4-Dichloro-phenyl)-ethoxy]-4-methoxy-benzoic acid 在 N-乙基吗啉 、 O-[(ethoxycarbonyl)cyanomethyleneamino]-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-{[1-(2-chloropyrimidin-4-yl)piperidin-4-yl]methyl}-3-[2-(2,4-dichlorophenyl)ethoxy]-4-methoxybenzamide
  参考文献：
  名称：

  Novel factor Xa inhibitors based on a benzoic acid scaffold and incorporating a neutral P1 ligand

  摘要：

  A series of novel, highly potent, achiral factor Xa inhibitors based on a benzoic acid scaffold and containing a chlorophenethyl moiety directed towards the protease S1 pocket is described. A number of structural features, such as the requirements of the P1, P4 and ester-binding pocket ligands were explored with respect to inhibition of factor Xa. Compound 46 was found to be the most potent compound in a series of antithrombotic secondary assays. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.059

文献信息

• New oxybenzamide derivatives useful for inhibiting factor Xa or VIIa
  申请人：——

  公开号：US20020198195A1

  公开（公告）日：2002-12-26

  The present invention relates to compounds comprising the following formula: R 0 —Q—X—Q′—W—U—V—G—M  (I) These compounds are useful as pharmacologically active compounds. They exhibit an antithrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardiovascular disorders such as thromboembolic diseases or restenoses. These compounds are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and/or factor VIIa (FVIIa), and can generally be used to treat, prevent, or cure conditions in which an undesired activity of factor Xa and/or factor VIIa is present, or where inhibition of factor Xa and/or factor VIIa is intended. The invention further relates to processes for the preparation of these compounds, methods of their use (e.g., as active ingredients in pharmaceuticals), and pharmaceutical preparations comprising them.

  本发明涉及包含以下公式的化合物： R 0 —Q—X—Q′—W—U—V—G—M  (I) 这些化合物作为药物活性化合物是有用的。它们展现出抗血栓作用，并适用于例如治疗和预防心血管疾病，如血栓栓塞性疾病或再狭窄。这些化合物是血液凝固酶因子Xa（FXa）和/或因子VIIa（FVIIa）的可逆性抑制剂，通常可用于治疗、预防或治愈存在因子Xa和/或因子VIIa不期望活性的情况，或旨在抑制因子Xa和/或因子VIIa的情况。本发明还涉及制备这些化合物的方法、它们的使用方法（例如，作为药品中的活性成分）以及包含它们的药物制剂。
• CETP INHIBITORS DERIVED FROM BENZOXAZOLE ARYLAMIDES
  申请人：HUNT Julianne A.

  公开号：US20100298288A1

  公开（公告）日：2010-11-25

  Compounds having the structure of Formula I1 including pharmaceutically acceptable salts of the compounds, are potent CETP (cholesterol ester transfer protein) inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis Atherosclerosis and its clinical consequences, coronary heart disease (CHD), stroke and penpheral vascular disease, represent a truly enormous burden to the health care systems of the industrialized world In formula I, A-B is an arylamide moiety

  具有I1式结构的化合物，包括化合物的药学上可接受的盐，是有效的CETP（胆固醇酯转移蛋白）抑制剂，可用于升高HDL-胆固醇，降低LDL-胆固醇，并用于治疗或预防动脉粥样硬化及其临床后果，如冠心病（CHD）、中风和周围血管疾病，对工业化国家的医疗保健系统构成巨大负担。在式I中，A-B是一个芳香酰胺基团。
• Structural Requirements for Factor Xa Inhibition by 3-Oxybenzamides with Neutral P1 Substituents:  Combining X-ray Crystallography, 3D-QSAR, and Tailored Scoring Functions
  作者：Hans Matter、David W. Will、Marc Nazaré,、Herman Schreuder、Volker Laux、Volkmar Wehner

  DOI：10.1021/jm049187l

  日期：2005.5.1

  The design, synthesis, and structure-activity relationship of 3-oxybenzamides as potent inhibitors of the coagulation protease factor Xa are described on the basis of X-ray structures, privileged structure motifs, and SAR information. A total of six X-ray structures of fXa/inhibitor complexes led us to identify the major protein-ligand interactions. The binding mode is characterized by a lipophilic dichlorophenyl substituent interacting with Tyr228 in the protease S1 pocket, while polar parts are accommodated in S4. This alignment in combination with docking allowed derivation of 3D-QSAR models and tailored scoring functions to rationalize biological affinity and provide guidelines for optimization. The resulting models showed good correlation coefficients and predictions of external test sets. Furthermore, they correspond to binding site topologies in terms of steric, electrostatic, and hydrophobic complementarity. Two approaches to derive tailored scoring functions combining binding site and ligand information led to predictive models with acceptable predictions of the external set. Good correlations to experimental affinities were obtained for both AFMoC (adaptation of fields for molecular comparison) and the novel TScore function. The SAR information from 3D-QSAR and tailored scoring functions agrees with all experimental data and provides guidelines and reasonable activity estimations for novel fXa inhibitors.
• OXYBENZAMIDES DERIVATIVES AS FACTOR XA INHIBITORS
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP1349847A1

  公开（公告）日：2003-10-08
• US8445480B2
  申请人：——

  公开号：US8445480B2

  公开（公告）日：2013-05-21