ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxylate | 917081-44-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxylate
• 英文别名: 5-(4-chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-hydroxymethyl-1H-pyrazole-3-carboxylic acid ethyl ester；ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-hydroxymethyl-1H-pyrazole-3-carboxylate；ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(hydroxymethyl)pyrazole-3-carboxylate
• CAS: 917081-44-8
• 化学式: C₁₉H₁₅Cl₃N₂O₃
• 分子量: 425.699
• InChiKey: NQBUUALGGAVGJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxylate 在 水 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 生成 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents

  摘要：

  The structural similarity between an MmpL3 inhibitor BM212, and a cannabinoid receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. Further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against Mycobacterium tuberculosis (H37Rv). The sila analogue 18a was found to be the most potent antimycobacterial compound (MIC, 31 ng/mL) from this series with an excellent selectivity index. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.07.009
• 作为产物：
  描述：

  ethyl 4-(bromomethyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-pyrazole-3-carboxylate 在 水 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 生成 ethyl 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-(hydroxymethyl)-1H-pyrazole-3-carboxylate
  参考文献：
  名称：

  [EN] FUSED PYRAZOLE DERIVATIVES AS CANNABINOID RECEPTOR MODULATORS
  [FR] DÉRIVÉS DE PYRAZOLE CONDENSÉS EN TANT QUE MODULATEURS DU RÉCEPTEUR CANNABINOÏDE

  摘要：

  本发明涉及一种新型的大麻素受体调节剂，其化学式为(I)，特别是大麻素1（CB1）或大麻素2（CB2）受体调节剂，以及用于治疗由大麻素受体调节的疾病、症状和/或疾患（如疼痛、神经退行性疾病、进食障碍、体重减轻或控制以及肥胖症）的用途。

  公开号：

  WO2009095752A1

文献信息

• [EN] FUSED PYRAZOLE DERIVATIVES AS CANNABINOID RECEPTOR MODULATORS<br/>[FR] DÉRIVÉS DE PYRAZOLE CONDENSÉS EN TANT QUE MODULATEURS DU RÉCEPTEUR CANNABINOÏDE
  申请人：GLENMARK PHARMACEUTICALS SA

  公开号：WO2009095752A1

  公开（公告）日：2009-08-06

  The present invention relates to novel cannabinoid receptor modulators of formula (I), in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2) receptor modulators, and uses thereof for treating diseases, conditions and/or disorders modulated by a cannabinoid receptor (such as pain, neurodegenrative disorders, eating disorders, weight loss or control, and obesity).

  本发明涉及一种新型的大麻素受体调节剂，其化学式为(I)，特别是大麻素1（CB1）或大麻素2（CB2）受体调节剂，以及用于治疗由大麻素受体调节的疾病、症状和/或疾患（如疼痛、神经退行性疾病、进食障碍、体重减轻或控制以及肥胖症）的用途。
• PYRAZOLE COMPOUNDS
  申请人：Shia Kak-Shan

  公开号：US20130085126A1

  公开（公告）日：2013-04-04

  Compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , and X are defined herein. Also disclosed are pharmaceutical compositions and methods related to use of these compounds.

  式（I）的化合物：其中R1、R2、R3、R4、R5和X在此处定义。还披露了与这些化合物的使用相关的药物组合物和方法。
• [EN] NOVEL PYRAZOLE DERIVATIVES WITH SILICON INCORPORATION<br/>[FR] NOUVEAUX DÉRIVÉS PYRAZOLES À SILICIUM INCORPORÉ
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2014181357A1

  公开（公告）日：2014-11-13

  Disclosed herein, novel sila analogs of pyrazole compounds of Formula-I and process for preparation thereof. Further the invention relates to pharmaceutical compositions comprising of novel sila analogs of pyrazole compounds of formula-I, which show better activity than other analogs as antiobesity molecules and also show antitubercular activities.

  本文披露了一种新型的嘧唑化合物Formula-I的硅类似物以及其制备方法。此外，本发明涉及包含新型嘧唑化合物Formula-I的硅类似物的制药组合物，这些组合物作为抗肥胖分子表现出比其他类似物更好的活性，并且还表现出抗结核活性。
• Cannabinoid Receptor Modulators
  申请人：Amengual Remi Alain

  公开号：US20080200527A1

  公开（公告）日：2008-08-21

  Compounds of formula (I), are cannabinoid CB1 receptors, useful, inter alia in the treatment of obesity: wherein A 1 is hydrogen, —COOH, or tetrazolyl, and A 2 is hydrogen, —COOH, tetrazolyl, —CN, —CF 3 , —COR 6 , —SO 2 R 6 , —OR 7 , —NR 7 R 8 , —NHCOR 6 , and —NR 7 SO 2 R 8 provided that one of A 1 and A 2 is either —COOH or tetrazolyl; p is 0 or 1 and A 3 is phenyl or cycloalkyl, either of which is optionally substituted with R 4 and/or R 5 ; q is 0 or 1; R 1 is a bond, or —(CH 2 ) a B 1 (CH 2 ) b — wherein a and b are independently 0, 1, 2 or 3 provided that a+b is not greater than 4, and B 1 is —CO—, —O—, —S—, —SO—, —SO 2 —, —CH 2 —, —CHOH— or —NR 7 —; R 2 is a bond, —CH 2 ) a B 1 (CH 2 ) b — or —[(CH 2 ) a B 1 (CH 2 ) b ] n -A 4 -[(CH 2 ) c B 2 (CH 2 ) d ] m — wherein a, b, and B 1 are as defined for R 1 ; B 2 is as defined for B 1 , c and d are independently 0, 1, 2 or 3; with the proviso that a+b+c+d is not greater than 6, n and m are independently 0 or 1 and A 4 is a monocarbocyclic or monoheterocyclic ring, having 3 to 8 ring atoms, optionally substituted with one or more of —F, —Cl, —Br, —CN, —CF 3 , C 1 -C 4 alkyl, cycloalkyl, —OR 9 , oxo or —NR 7 R 8 ; R 3 is hydrogen, C 1 -C 4 alkyl, cycloalkyl, —CF 3 , —OR 9 , —NR 7 R 8 , —(CH 2 ) s COR 6 , —(CH 2 ) s SO 2 R 6 , —(CH 2 ) s NR 7 COR 6 , —(CH 2 ) s NR 7 COOR 8 , —(CH 2 ) s NR 7 SO 2 R 6 , wherein s is 1, 2, 3 or 4; R 4 and R 5 independently —R 9 , —CN, —F, —Cl, —Br, —OR 9 , —NR 7 R 8 , —NR 7 COR 6 , —NR 7 SO 2 R 6 , —COR 6 , —SR 9 , —SOR 9 , —SO 2 R 6 , (C 1 -C 4 alkyl)OR 9 , —(C 1 -C 4 alkyl)NR 7 R 8 , —(C 1 -C 4 alkyl)NR 7 COR 6 , C 1 -C 4 alkyl)NR 7 COOR 8 , —(C 1 -C 4 alkyl)NR 7 SO 2 R 6 , —(C 1 -C 4 alkyl)COR 6 , —(C 1 -C 4 alkyl)SO 2 R 6 , —NR 7 COOR 8 , or [N—(C 1 -C 4 alkyl)]-tetrazolyl; R 6 is C 1 -C 4 alkyl, cycloalkyl, —CF 3 or —NR 7 R 8 ; R 7 and R 8 are independently hydrogen, C 1 -C 4 alkyl or cycloalkyl; and R 9 is hydrogen, C 1 -C 4 alkyl, cycloalkyl, fully or partially fluorinated C 1 -C 4 alkyl.

  公式（I）的化合物是大麻素CB1受体，可用于治疗肥胖症等疾病：其中A1是氢，-COOH或四唑基，而A2是氢，-COOH，四唑基，-CN，-CF3，-COR6，-SO2R6，-OR7，-NR7R8，-NHCOR6和-NR7SO2R8，前提是A1和A2中的一个是-COOH或四唑基；p为0或1，A3为苯基或环烷基，其中任意一个都可以用R4和/或R5取代；q为0或1；R1是键，或-（CH2）aB1（CH2）b-，其中a和b独立地为0、1、2或3，前提是a+b不大于4，B1是-CO-，-O-，-S-，-SO-，-SO2-，-CH2-，-CHOH-或-NR7-；R2是键，-（CH2）aB1（CH2）b-或-[(CH2)aB1(CH2)b]n-A4-[(CH2)cB2(CH2)d]m-，其中a、b和B1如R1所定义；B2如B1定义，c和d独立地为0、1、2或3；前提是a+b+c+d不大于6，n和m独立地为0或1，A4是具有3到8个环原子的单环芳烃或单环杂环，可选地取代一个或多个-F、-Cl、-Br、-CN、-CF3、C1-C4烷基、环烷基、-OR9、氧代或-NR7R8；R3是氢、C1-C4烷基、环烷基、-CF3、-OR9、-NR7R8、-（CH2）sCOR6、-（CH2）sSO2R6、-（CH2）sNR7COR6、-（CH2）sNR7COOR8、-（CH2）sNR7SO2R6，其中s为1、2、3或4；R4和R5独立地为-R9、-CN、-F、-Cl、-Br、-OR9、-NR7R8、-NR7COR6、-NR7SO2R6、-COR6、-SR9、-SOR9、-SO2R6、（C1-C4烷基）OR9、-（C1-C4烷基）NR7R8、-（C1-C4烷基）NR7COR6、C1-C4烷基）NR7COOR8、-（C1-C4烷基）NR7SO2R6、-（C1-C4烷基）COR6、-（C1-C4烷基）SO2R6、-NR7COOR8或[N-（C1-C4烷基）]-四唑基；R6是C1-C4烷基、环烷基、-CF3或-NR7R8；R7和R8独立地为氢、C1-C4烷基或环烷基；R9是氢、C1-C4烷基、环烷基、全氟或部分氟化的C1-C4烷基。
• Pentacycle derivatives as cannabinoid CB1 receptor ligands
  作者：Suk Ho Lee、Hee Jeong Seo、Min Ju Kim、Suk Youn Kang、Sung-Han Lee、Kwangwoo Ahn、MinWoo Lee、Ho-Kyun Han、Jeongmin Kim、Jinhwa Lee

  DOI：10.1016/j.bmcl.2009.10.015

  日期：2009.12

  Cannabinoid CB-1 receptors have been the focus of extensive studies since the first clinical results of rimonabant (SR141716) for the treatment of obesity and obesity-related metabolic disorders were reported in 2001. To further evaluate the properties of CB receptors, we have designed and efficiently prepared a series of pentacycle derivatives. Five of the new compounds which displayed high in vitro rCB1 binding affinities were assayed for binding to hCB2 receptor. Noticeably, 2-(5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-(5-methyl- 1,3,4-thiadiazol-2-yl)-1H-pyrazol-3-yl)-5-(1-(trifluoromethyl) cyclopropyl)-1,3,4-oxadiazole (16l) demonstrated good binding affinity and decent selectivity for rCB1 receptor (IC50 = 1.72 nM, hCB2/rCB1 = 142). (C) 2009 Elsevier Ltd. All rights reserved.