4-[(1-pyrrolidinyl)methyl]benzoic acid hydrochloride | 193968-71-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[(1-pyrrolidinyl)methyl]benzoic acid hydrochloride
• 英文别名: 4-[2-(1-pyrrolidinyl)methyl]benzoic acid hydrochloride；4-(1-pyrrolidinylmethyl)benzoic acid hydrochloride；4-(Pyrrolidin-1-ylmethyl)benzoic acid hydrochloride；4-(pyrrolidin-1-ylmethyl)benzoic acid;hydrochloride
• CAS: 193968-71-7
• 化学式: C₁₂H₁₅NO₂*ClH
• mdl: MFCD15201458
• 分子量: 241.718
• InChiKey: YVBBCFWJPVGECC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.75
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(1-pyrrolidinyl)methyl]benzoic acid hydrochloride 在 N-甲基吗啉 、 sodium hydroxide 、 氯甲酸异丁酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 N-(N-(4-pyrrolidin-1-ylmethylbenzoyl)-L-phenylalanyl)-L-phenylalanol
  参考文献：
  名称：

  Synthesis and biological evaluation of Matijing-Su derivatives as potent anti-HBV agents

  摘要：

  A series of Matijing-Su (MTS, N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol) derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity in 2.2.15 cells. The IC50 of compounds 14a (0.71 mu M), 13c (2.85 mu M), 13b (4.37 mu M), etc. and the selective index of 13g (161.01), 13c (90.45), 13a (85.09) etc. of the inhibition on the replication of HBV DNA were better than those of the positive control lamivudine (IC50: 82.42 mu M, SI: 41.59). Compounds 13o, 13p, and 16a also exhibited significant anti-HBV activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.001
• 作为产物：
  描述：

  对甲基苯甲酸甲酯 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 水 、 potassium carbonate 、 potassium iodide 作用下， 以 四氯化碳 、 乙醇 为溶剂， 反应 12.0h， 生成 4-[(1-pyrrolidinyl)methyl]benzoic acid hydrochloride
  参考文献：
  名称：

  Synthesis and biological evaluation of Matijing-Su derivatives as potent anti-HBV agents

  摘要：

  A series of Matijing-Su (MTS, N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol) derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity in 2.2.15 cells. The IC50 of compounds 14a (0.71 mu M), 13c (2.85 mu M), 13b (4.37 mu M), etc. and the selective index of 13g (161.01), 13c (90.45), 13a (85.09) etc. of the inhibition on the replication of HBV DNA were better than those of the positive control lamivudine (IC50: 82.42 mu M, SI: 41.59). Compounds 13o, 13p, and 16a also exhibited significant anti-HBV activity. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.001

文献信息

• Antithrombotic diamines
  申请人：Eli Lilly and Company

  公开号：US06025382A1

  公开（公告）日：2000-02-15

  This application relates to the use as thrombin inhibitors, coagulation inhibitors and thromboembolic disorder agents of diamines of formula I as defined herein. It also provides novel compounds of formula I, processes and intermediates for their preparation, and pharmaceutical formulations comprising the novel compounds of formula I.

  该应用涉及将I式中所定义的二胺用作凝血酶抑制剂、凝血抑制剂和血栓栓塞性疾病药剂。它还提供了I式的新化合物，其制备方法和中间体，以及包含这些新化合物的药物配方。
• [EN] ANTITHROMBOTIC DIAMINES<br/>[FR] DIAMINES ANTITHROMBOTIQUES
  申请人：ELI LILLY AND COMPANY

  公开号：WO1997025033A1

  公开（公告）日：1997-07-17

  (EN) This application relates to the use as thrombin inhibitors, coagulation inhibitors and thromboembolic disorder agents of diamines of formula (I) as defined herein. It also provides novel compounds of formula (I), processes and intermediates for their preparation, and pharmaceutical formulations comprising the novel compounds of formula (I).(FR) La présente invention concerne l'utilisation, comme inhibiteurs de thrombine, inhibiteurs de coagulation et agents destinés aux désordres de la thromboembolie, de diamines de formule I telle qu'elle est définie dans la description. L'invention concerne aussi des composés nouveaux de formule I, des procédés et des produits intermédiaires pour leur préparation, et des formulations pharmaceutiques comprenant les composés nouveaux de formule I.

  该应用涉及使用公式（I）所定义的二胺作为凝血酶抑制剂、凝血抑制剂和血栓栓塞疾病药物的用途。它还提供了公式（I）的新化合物、其制备过程和中间体，以及包含公式（I）的新药物配方。
• Amine derivative
  申请人：Ishihara Yuji

  公开号：US20060128690A1

  公开（公告）日：2006-06-15

  The present invention provides a compound represented by the formula wherein Ar 1 is a cyclic group optionally having substituent(s); R is a hydrogen atom, an optionally halogenated C 1-6 alkyl, a phenyl optionally having substituent(s) or a pyridyl optionally having substituent(s); Ra 1 , Ra 2 , Ra 3 and Ra 4 are the same or different and each is a hydrogen atom, an optionally halogenated C 1-6 alkyl or the like; Ar is a monocyclic aromatic ring optionally having substituent(s); Y is an optionally halogenated alkylene group; and R 1 and R 2 are (1) the same or different and each is a hydrogen atom or a C 1-6 alkyl, (2) R 1 and R 2 form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom, or (3) R 1 and Y form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom, and R 2 is a hydrogen atom or a C 1-6 alkyl; provided that when the nitrogen-containing heterocycle formed by R 1 and R 2 together with the adjacent nitrogen atom is a piperazine, or when R is a C 1-4 alkyl, Ar 1 is a cyclic group having substituent(s), or a salt thereof, having a melanin-concentrating hormone antagonistic action and useful as an agent for the prophylaxis or treatment of obesity and the like.

  本发明提供了一种化合物，其表示为式子： 其中，Ar1是一个环状基团，可以具有取代基；R是氢原子，可选卤代的C1-6烷基，苯环，可以具有取代基，或者吡啶环，可以具有取代基；Ra1，Ra2，Ra3和Ra4相同或不同，每个都是氢原子，可选卤代的C1-6烷基或类似物；Ar是一个单环芳香环，可以具有取代基；Y是可选卤代的脂肪族烷基；R1和R2是（1）相同或不同，每个都是氢原子或C1-6烷基，（2）R1和R2与相邻的氮原子一起形成含氮杂环，可以具有取代基，或（3）R1和Y与相邻的氮原子一起形成含氮杂环，可以具有取代基，并且R2是氢原子或C1-6烷基；但是当R1和R2与相邻的氮原子一起形成哌嗪环，或当R是C1-4烷基，Ar1是具有取代基的环状基团或其盐时，该化合物具有黑色素浓集激素拮抗作用，可用作预防或治疗肥胖症等药物。
• AMINE DERIVATIVE
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1593667A1

  公开（公告）日：2005-11-09

  The present invention provides a compound represented by the formula wherein Ar1 is a cyclic group optionally having substituent(s); R is a hydrogen atom, an optionally halogenated C1-6 alkyl, a phenyl optionally having substituent(s) or a pyridyl optionally having substituent(s); Ra1, Ra2, Ra3 and Ra4 are the same or different and each is a hydrogen atom, an optionally halogenated C1-6 alkyl or the like; Ar is a monocyclic aromatic ring optionally having substituent(s); Y is an optionally halogenated alkylene group; and R1 and R2 are (1) the same or different and each is a hydrogen atom or a C1-6 alkyl, (2) R1 and R2 form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom, or (3) R1 and Y form a nitrogen-containing heterocycle optionally having substituent(s) together with the adjacent nitrogen atom, and R2 is a hydrogen atom or a C1-6 alkyl; provided that when the nitrogen-containing heterocycle formed by R1 and R2 together with the adjacent nitrogen atom is a piperazine, or when R is a C1-4 alkyl, Ar1 is a cyclic group having substituent(s), or a salt thereof, having a melanin-concentrating hormone antagonistic action and useful as an agent for the prophylaxis or treatment of obesity and the like.

  本发明提供了一种由式表示的化合物 其中 Ar1 是任选具有取代基的环状基团； R 是氢原子、任选卤化的 C1-6 烷基、任选具有取代基的苯基或任选具有取代基的吡啶基； Ra1、Ra2、Ra3 和 Ra4 相同或不同，各自为氢原子、任选卤代的 C1-6 烷基或类似物； Ar 是单环芳香环，可选择具有取代基； Y 是任选卤代亚烷基；以及 R1 和 R2 (1) 相同或不同，且各自为氢原子或 C1-6 烷基；(2) R1 和 R2 组成含氮杂环，可选择与相邻氮原子一起具有取代基；或 (3) R1 和 Y 组成含氮杂环，可选择与相邻氮原子一起具有取代基，且 R2 为氢原子或 C1-6 烷基； 条件是当 R1 和 R2 与相邻氮原子一起形成的含氮杂环是哌嗪时，或当 R 是 C1-4 烷基时，Ar1 是具有取代基的环状基团或其盐，具有黑色素浓缩激素拮抗作用，可用作预防或治疗肥胖症等的药物。
• Diamino Benzo[<i>b</i>]thiophene Derivatives as a Novel Class of Active Site Directed Thrombin Inhibitors. 5. Potency, Efficacy, and Pharmacokinetic Properties of Modified C-3 Side Chain Derivatives
  作者：Daniel J. Sall、Dianna L. Bailey、Jolie A. Bastian、John A. Buben、Nickolay Y. Chirgadze、Amy C. Clemens-Smith、Michael L. Denney、Matthew J. Fisher、Deborah D. Giera、Donetta S. Gifford-Moore、Richard W. Harper、Lea M. Johnson、Valentine J. Klimkowski、Todd J. Kohn、Ho-Shen Lin、Jefferson R. McCowan、Alan D. Palkowitz、Michael E. Richett、Gerald F. Smith、David W. Snyder、Kumiko Takeuchi、John E. Toth、Minsheng Zhang

  DOI：10.1021/jm9903388

  日期：2000.2.1

  A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit la led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271 x 10(6) L/mol, respectively) represent 2200- and 2900-fold increases in potency over the starting lead la. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of derivatives 28c and 31c were determined, and they compare favorably with the clinical agent H-R-1-[4aS,-8aS]perhydroisoquinolyl-prolyl-arginyl aldehyde (D-Piq-Pro-Arg-H; 32). The more potent members of this series have been studied in an arterial/venous shunt (AV shunt) model of thrombosis and were found to be efficacious in reducing clot formation. However, their efficacy is currently limited by their rapid and extensive distribution following administration.