1-(2-氯苯基)-4-甲基-5-(4-甲氧基苯基)-1H-吡唑-3-羧酸乙酯 | 501426-50-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(2-氯苯基)-4-甲基-5-(4-甲氧基苯基)-1H-吡唑-3-羧酸乙酯
• 英文名称: 1-(2-chlorophenyl)-4-methyl-5-(4-methoxyphenyl)-1H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: 1-(2-chloro-phenyl)-5-(4-methoxy-phenyl)-4-methyl-1H-pyrazole-3-carboxylic acid ethyl ester；Ethyl 1-(2-chlorophenyl)-5-(4-methoxyphenyl)-4-methylpyrazole-3-carboxylate
• CAS: 501426-50-2
• 化学式: C₂₀H₁₉ClN₂O₃
• 分子量: 370.835
• InChiKey: LUZYONGMXTXTQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  53.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-氯苯基)-4-甲基-5-(4-甲氧基苯基)-1H-吡唑-3-羧酸乙酯 在 氢氧化钾 、 氯化亚砜 作用下， 以 甲醇 、 甲苯 为溶剂， 生成
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationship, and Evaluation of SR141716 Analogues:  Development of Central Cannabinoid Receptor Ligands with Lower Lipophilicity

  摘要：

  Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented.

  DOI：

  10.1021/jm020157x
• 作为产物：
  描述：

  2-氯苯肼盐酸盐 、 草酸二乙酯 、 对甲氧基苯丙酮 在 lithium hexamethyldisilazane 、 溶剂黄146 作用下， 以 乙醚 、 乙醇 为溶剂， 以80%的产率得到1-(2-氯苯基)-4-甲基-5-(4-甲氧基苯基)-1H-吡唑-3-羧酸乙酯
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationship, and Evaluation of SR141716 Analogues:  Development of Central Cannabinoid Receptor Ligands with Lower Lipophilicity

  摘要：

  Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented.

  DOI：

  10.1021/jm020157x

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。
• WO2006/133926
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.
• Synthesis, Structure−Activity Relationship, and Evaluation of SR141716 Analogues:  Development of Central Cannabinoid Receptor Ligands with Lower Lipophilicity
  作者：Reeti Katoch-Rouse、Olga A. Pavlova、Tara Caulder、Alexander F. Hoffman、Alexey G. Mukhin、Andrew G. Horti

  DOI：10.1021/jm020157x

  日期：2003.2.1

  Exploration of the central CB1 cannabinoid receptors using positron emission tomography (PET) will allow for an understanding of the pharmacological and physiological role played by these receptors in the CNS. Current tracers are highly lipophilic compounds that exhibit very high nonspecific to specific binding ratios and as a result are inapt for use in humans. We have synthesized a series of less lipophilic analogues of SR141716 to serve as potential radioligands. Binding affinities of the series and a functional electrophysiological assay of three of our compounds have been presented.