1-(4-(methylamino)phenyl)piperidin-2-one | 444002-68-0

• 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: 1-(4-(methylamino)phenyl)piperidin-2-one
• 英文别名: 1-(4-methylaminophenyl)piperidin-2-one；1-[4-(Methylamino)phenyl]piperidin-2-one
• CAS: 444002-68-0
• 化学式: C₁₂H₁₆N₂O
• 分子量: 204.272
• InChiKey: APHVCOSZWWIXIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-(methylamino)phenyl)piperidin-2-one 在 4-二甲氨基吡啶 、 10% Pd(OH)₂ on C 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 叔丁醇 为溶剂， 生成 (S)-N-methyl-2-(4-methylbenzoyl)-N-(4-(2-oxopiperidin-1-yl)phenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032
• 作为产物：
  描述：

  哌啶酮 、 4-溴-N-甲基苯胺 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 甲苯 为溶剂， 生成 1-(4-(methylamino)phenyl)piperidin-2-one
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032

文献信息

• SUBSTITUTED NAPHTHYRIDINES AND USE THEREOF AS MEDICINES
  申请人：Hoffmann Matthias

  公开号：US20110201608A1

  公开（公告）日：2011-08-18

  The invention relates to new substituted naphthyridines of formula 1, as well as pharmacologically acceptable salts, diastereomers, enantiomers, racemates, hydrates or solvates thereof, wherein R 1 denotes a group A selected from among —O—R 3 , —NR 3 R 4 , —CR 3 R 4 R 5 , -(ethyne)-R 3 , —S—R 3 , —SO—R 3 and SO 2 —R 3 or R 1 denotes a group B selected from among C 6-10 -aryl, five- to ten-membered, mono- or bicyclic heteroaryl with 1-3 heteroatoms selected independently of one another from among N, O and S; while this heteroaryl is linked to the structure according to formula 1 via either a C atom or an N atom, three- to ten-membered, mono- or bicyclic, saturated or partially saturated heterocyclic group with 1-3 heteroatoms selected independently of one another from among N, O and S, while this heterocyclic group is linked to the structure according to formula 1 via either a C atom or an N atom, and 5- to 11-membered spiro group which may optionally contain 1, 2 or 3 heteroatoms selected independently of one another from among N, O and S, while this spiro group is linked to the structure according to formula 1 via either a C atom or an N atom, while this group B may optionally be substituted as described in claim 1 and wherein R 2 is and R 3 , R 4 , R 5 , R 6 , R 6′ , R 7 , R 8 , R 9 , R 10 , V, n and m may have the meanings given in claim 1 , as well as pharmaceutical compositions containing these compounds.

  该发明涉及公式1的新取代萘啉类化合物，以及其药理学上可接受的盐、对映体、对映异构体、外消旋体、水合物或溶剂合物，其中R1表示从以下选取的A基团，包括—O—R3、—NR3R4、—CR3R4R5、-(乙炔)-R3、—S—R3、—SO—R3和SO2—R3，或R1表示从以下选取的B基团，包括C6-10-芳基、含有1-3个异原子（N、O和S）的五至十元杂环芳基，而此杂环芳基通过碳原子或氮原子与公式1中的结构连接，含有1-3个异原子（N、O和S）的三至十元杂环饱和或部分饱和环族基团，而此杂环基团通过碳原子或氮原子与公式1中的结构连接，以及可能含有1、2或3个异原子（N、O和S）的五至十一元螺环基团，而此螺环基团通过碳原子或氮原子与公式1中的结构连接，其中该B基团可以选择地按照权利要求1中所述进行取代，R2为，R3、R4、R5、R6、R6′、R7、R8、R9、R10、V、n和m的含义如权利要求1中所述，以及含有这些化合物的药物组合物。
• Phenyl derivatives
  申请人：——

  公开号：US20040087582A1

  公开（公告）日：2004-05-06

  Novel compounds of the formula I in which W, X, Y, T, R 1 and R 2 are as defined in Patent claim 1, are inhibitors of coagulation factor Xa and can be employed for the prophylaxis and/or therapy of thromboembolic disorders. 1

  公式I中的新化合物，其中W、X、Y、T、R1和R2如专利权要求1所定义，是凝血因子Xa的抑制剂，可用于预防和/或治疗血栓栓塞疾病。
• PHENYL DERIVATIVES
  申请人：MERCK PATENT GmbH

  公开号：EP1351938A1

  公开（公告）日：2003-10-15
• AMINE DERIVATIVES HAVING NPY Y5 RECEPTOR ANTAGONISTIC ACTIVITY AND THE USES THEREOF
  申请人：OKUNO Takayuki

  公开号：US20100273842A1

  公开（公告）日：2010-10-28

  This invention provides an anorectic or anti-obesity composition comprising a compound of the formula (I): a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is optionally substituted lower alkyl, Y is —S(O) n — wherein n is 1 or 2, or —CO—, R 2 is hydrogen or lower alkyl, R 7 is hydrogen or lower alkyl, X is lower alkylene, lower alkenylene, arylene, cycloalkylene or the like, and Z is lower alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl or the like.
• US7199149B2
  申请人：——

  公开号：US7199149B2

  公开（公告）日：2007-04-03