1-(2-chloro-phenyl)-5-(4-chloro-phenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid 4-bromo-benzylamide | 917081-48-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(2-chloro-phenyl)-5-(4-chloro-phenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid 4-bromo-benzylamide
• 英文别名: N-(4-bromobenzyl)-1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-(cyanomethyl)-1H-pyrazole-3-carboxamide；N-[(4-bromophenyl)methyl]-1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-(cyanomethyl)pyrazole-3-carboxamide
• CAS: 917081-48-2
• 化学式: C₂₅H₁₇BrCl₂N₄O
• 分子量: 540.246
• InChiKey: JDGFLFBQAWOEJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  70.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(2-chloro-phenyl)-5-(4-chloro-phenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid 4-bromo-benzylamide 在 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 三甲基氯硅烷 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.08h， 生成
  参考文献：
  名称：

  WO2006/133926

  摘要：

  公开号：
• 作为产物：
  描述：

  5-(4-chlorophenyl)-1-(2-chlorophenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid 、 对溴苄胺 在 1-羟基苯并三唑 作用下， 以 二氯甲烷 为溶剂， 生成 1-(2-chloro-phenyl)-5-(4-chloro-phenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid 4-bromo-benzylamide
  参考文献：
  名称：

  Exploring SAR features in diverse library of 4-cyanomethyl-pyrazole-3-carboxamides suitable for further elaborations as CB1 antagonists

  摘要：

  A chemically diverse library of secondary and tertiary 4-cyanomethyl-1,5-diphenyl-1H-pyrazole-3-carboxamides was synthesized to enable mapping of the SAR, in the eastern amide region, with regard to CB1 antagonist activity, This study was initiated as a prelude to the design and synthesis of possible CB1 antagonists that do not readily pass the blood-brain-barrier. In general a range of modi. cations were found to be tolerated in this part of the molecule, although polar and especially charged groups did to a degree reduce the CB1 antagonistic activity. Several compounds with single-digit or even sub-nanomolar potency, suitable for further elaboration of the nitrile moiety, were identified. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.11.047

文献信息

• 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。
• PYRAZOLE DERIVATES AS CANNABINOID RECEPTOR MODULATORS
  申请人：Carex SA

  公开号：EP1928859A1

  公开（公告）日：2008-06-11
• [EN] PYRAZOLE DERIVATES AS CANNABINOID RECEPTOR MODULATORS<br/>[FR] DERIVES DE PYRAZOLE UTILISES COMME MODULATEURS DU RECEPTEUR CANNABINOIDE
  申请人：CAREX SA

  公开号：WO2006133926A1

  公开（公告）日：2006-12-21

  [EN] Compounds of formula (I), are cannabinoid CB1 receptors, useful, inter alia in the treatment of obesity: (I) wherein A₁ is hydrogen, -COOH, or tetrazolyl, and A₂ is hydrogen, -COOH, tetrazolyl, -CN, -CF₃, -COR₆, -SO₂R₆, -OR₇, -NR₇R₈, -NHCOR₆, and -NR₇SO₂R₈ provided that one of A₁ and A₂ is either -COOH or tetrazolyl; p is O or 1 and A₃ is phenyl or cycloalkyl, either of which is optionally substituted with R₄ and/or R₅; q is O or 1 ; R₁ is a bond, or - (CH₂)_aB₁(CH₂)_b- wherein a and b are independently O, 1 , 2 or 3 provided that a+b is not greater than 4, and B₁ is -CO-, -0-, -S-, -SO-, -SO₂-, -CH₂-, -CHOH- or -NR₇-; R₂ is a bond, -(CH₂)_aB₁ (CH₂)_b- or -[(CH₂)_aB₁ (CH₂)_b]_n-A_4-[(CH₂)_cB₂(CH₂)d]m- wherein a, b, and B1 are as defined for R1; B2 is as defined for B1, 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 O or 1 and A₄ is a monocarbocyclic or monoheterocyclic ring, having 3 to 8 ring atoms, optionally substituted with one or more of -F, -Cl, -Br, -CN, -CF₃, C₁-C₄ alkyl, cycloalkyl, -OR₉, oxo or -NR₇R₈; R₃ is hydrogen, C₁-C₄ alkyl, cycloalkyl, -CF₃, -OR₉, -NR₇R₈, -(CH₂)SCOR₆, -(CH₂)SSO₂R₆, -(CH₂)SNR₇COR₆, -(CH₂)SNR₇COOR₈, -(CH₂)SNR7SO2R6, wherein s is 1 , 2, 3 or 4; R₄ and R₅ independently -R₉, -CN, -F, -Cl, -Br, -OR₉, -NR7R₈, -NR₇COR₆, -NR₇SO₂R₆, -COR₆, -SR₉, -SOR₉, -SO₂R₆, (C1-C₄ alkyl)OR₉, -(C₁-C₄ alkyl)NR₇R₈, -(C₁-C₄ alkyl)NR₇COR₆, C₁-C₄ alkyl)NR₇COOR₈, -(C₁-C₄ alkyl)NR₇SO₂R₆, -(C₁-C₄ alkyl)COR₆, -(C₁-C₄ alkyl)SO₂R₆, -NR₇COOR₈, or [N-(C₁-C₄ alkyl)]- tetrazolyl; R₆ is C₁-C₄ alkyl, cycloalkyl, -CF₃ or -NR₇R₈; R₇ and R₈ are independently hydrogen, C₁-C₄ alkyl or cycloalkyl and R₉ is hydrogen, C₁-C₄ alkyl, cycloalkyl, fully or partially fluorinated C₁-C₄ alkyl.
  [FR] L'invention concerne des composés représentés par la formule (I), qui sont de récepteurs cannabinoïdes CB1, utiles notamment pour le traitement de l'obésité: (I) A₁ représente hydrogène, -COOH, ou tétrazolyle, et A₂ représente hydrogène, -COOH, tétrazolyle, -CN, -CF₃, -COR₆, -SO₂R₆, -OR₇, -NR₇R₈, -NHCOR₆, et -NR₇SO₂R₈ à condition que A₁ ou A₂ représente soit COOH, soit tétrazolyle; p représente O ou 1, et A₃ représente phényle ou cycloalkyle, qui peuvent chacun être éventuellement substitués par R₄ et/ou R₅; q représente O ou 1; R₁ représente une liaison, ou - (CH₂)_aB₁(CH₂)_b-, a et b représentant séparément O, 1, 2 ou 3, à condition que a+b ne soit pas supérieur à 4, et B₁ représente -CO-, -0-, -S-, -SO-, -SO₂-, -CH₂-, -CHOH- ou -NR₇-; R₂ représente une liaison, -(CH₂)_aB₁ (CH₂)_b- ou -[(CH₂)_aB₁ (CH₂)_b]_n-A_4-[(CH₂)_cB₂(CH₂)d]m-, dans laquelle a, b, et B1 ont les mêmes définitions que dans R1; B2 correspond à la définition de B1, c et d représentent séparément 0,1, 2 ou 3; à condition que a+b+c+d ne soient pas supérieurs à 6, n et m représentent séparément O ou 1, et A₄ représente un cycle monocarbocyclique ou monohétérocyclique comprenant de 3 à 8 atomes, éventuellement substitué par un ou plusieurs des groupes suivants: -F, -Cl, -Br, -CN, -CF₃, C₁-C₄ alkyle, cycloalkyle, -OR₉, oxo ou -NR₇R₈; R₃ représente hydrogène, C₁-C₄ alkyle, cycloalkyle, -CF₃, -OR₉, -NR₇R₈, -(CH₂)SCOR₆, -(CH₂)SSO₂R₆, -(CH₂)SNR₇COR₆, -(CH₂)SNR₇COOR₈, -(CH₂)SNR₇SO₂R₆, dans lesquels s représente 1, 2, 3 ou 4; R₄ et R₅ représentent séparément -R₉, -CN, -F, -Cl, -Br, -OR₉, -NR7R₈, -NR₇COR₆, -NR₇SO₂R₆, -COR₆, -SR₉, -SOR₉, -SO₂R₆, (C1-C₄ alkyle)OR₉, -(C₁-C₄ alkyle)NR₇R₈, -(C₁-C₄ alkyle)NR₇COR₆, C₁-C₄ alkyle)NR₇COOR₈, -(C₁-C₄ alkyl)NR₇SO₂R₆, -(C₁-C₄ alkyl)COR₆, -(C₁-C₄ alkyl)SO₂R₆, -NR₇COOR₈, ou [N-(C₁-C₄ alkyle)]- tétrazolyle; R₆ représente C₁-C₄ alkyle, cycloalkyle, -CF₃ ou -NR₇R₈; R₇ et R₈ représentent séparément hydrogène, C₁-C₄ alkyle ou cycloalkyle, et R₉ représente hydrogène, C₁-C₄ alkyle, cycloalkyle, C₁-C₄ alkyle, entièrement ou partiellement fluoré.
• WO2006/133926
  申请人：——

  公开号：——

  公开（公告）日：——
• Exploring SAR features in diverse library of 4-cyanomethyl-pyrazole-3-carboxamides suitable for further elaborations as CB1 antagonists
  作者：Martin Cooper、Jean-Marie Receveur、Emelie Bjurling、Pia K. Nørregaard、Peter Aadal Nielsen、Niklas Sköld、Thomas Högberg

  DOI：10.1016/j.bmcl.2009.11.047

  日期：2010.1

  A chemically diverse library of secondary and tertiary 4-cyanomethyl-1,5-diphenyl-1H-pyrazole-3-carboxamides was synthesized to enable mapping of the SAR, in the eastern amide region, with regard to CB1 antagonist activity, This study was initiated as a prelude to the design and synthesis of possible CB1 antagonists that do not readily pass the blood-brain-barrier. In general a range of modi. cations were found to be tolerated in this part of the molecule, although polar and especially charged groups did to a degree reduce the CB1 antagonistic activity. Several compounds with single-digit or even sub-nanomolar potency, suitable for further elaboration of the nitrile moiety, were identified. (C) 2009 Elsevier Ltd. All rights reserved.