2-(1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-phenylpiperazine-1-carbonyl)-1H-pyrazol-4-yl)acetonitrile | 1034592-72-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-phenylpiperazine-1-carbonyl)-1H-pyrazol-4-yl)acetonitrile
• 英文别名: 2-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-phenylpiperazine-1-carbonyl)pyrazol-4-yl]acetonitrile
• CAS: 1034592-72-7
• 化学式: C₂₈H₂₃Cl₂N₅O
• 分子量: 516.43
• InChiKey: JJKVOVGHJDQLCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  65.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-1 H-pyrazole-3-carboxylate 、 、 去甲哌替啶 、 2-(1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-phenylpiperazine-1-carbonyl)-1H-pyrazol-4-yl)acetonitrile 以to give 1-[1-(2-chloro-phenyl)-5-(4-chloro-phenyl)-4-methyl-1H-pyrazole-3-carbonyl]-4-phenyl-piperidine-4-carboxylic acid ethyl ester的产率得到1-[1-(2-chloro-phenyl)-5-(4-chloro-phenyl)-4-methyl-1H-pyrazole-3-carbonyl]-4-phenyl-piperidine-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  Modulators of CB1 Receptors

  摘要：

  式(I)的化合物抑制CB1受体的正常信号活动，因此可用于治疗由CB1受体信号活动介导的疾病或症状，例如肥胖和超重的治疗，预防体重增加，直接或间接与肥胖和超重相关的疾病和症状的治疗：其中A1是氢，-COOH或四唑基；p和q独立地为0或1；A3是苯基或环烷基，其中任一可选地用R4和/或R5取代；R4和R5独立地为-R9，-CN，-F，-Cl，-Br，-OR9，-NR7R8，-NR7COR6，-NR7SO2R6，-COR6，-SR9，-SOR9或-SO2R6；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为氢，C1-C4烷基，C1-C4烷氧基，C1-C4烷氧基（C1-C4烷基）-，环烷基或完全或部分氟化的C1-C4烷基；R1(i)为键；（ii）为式-（CH2）aB1（CH2）b的二价基团，其中a和b独立地为O，1，2或3，前提是a+b为1，2或3，B1为-CO-，-O-，-S-，-SO-，-SO2-，-CH2-，-CHCH3-，-CHOH-或-NR7-；或（iii）为从-C（R10）（R11）- *，-C（R10）（R11）-O- *，-C（R10）（R11）CH2- *，-C（R10）（R11）CH2- O- *，-CH2C（R10）（R11）- *，-CH2C（R10）（R11）-O- *，-CH2-O-C（R10）（R11）- *和-C（R10）（R11）-O-CH2- *中选择的二价基团，其中由星号表示的键连接到吡唑环；Z如规范中所定义；R10为氢，R11为（C1-C3）烷基或-OH；或R10和R11均为（C1-C3）烷基；或R10和R11与它们连接的碳原子一起形成（C3-C5）环烷基环。

  公开号：

  US20100144701A1
• 作为产物：
  描述：

  N-苯基哌嗪 、 5-(4-chlorophenyl)-1-(2-chlorophenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid 在 1-羟基苯并三唑 作用下， 以 二氯甲烷 为溶剂， 生成 2-(1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-phenylpiperazine-1-carbonyl)-1H-pyrazol-4-yl)acetonitrile
  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

• Modulators of CB1 Receptors
  申请人：Cooper Martin

  公开号：US20100144701A1

  公开（公告）日：2010-06-10

  Compounds of formula (I) suppress the normal signalling activity CB1 receptors, and are thus useful in the treatment of diseases or conditions which are mediated by CB1 receptor signalling activity, such as treatment of obesity and overweight, prevention of weigh gain, treatment of diseases and conditions directly or indirectly associated with obesity and overweight: wherein A 1 is hydrogen, —COOH,or tetrazolyl; p and q are independently 0 or 1; A3 is phenyl or cycloalkyl, either of which is optionally substituted with R 4 and/or R 5 ; R 4 and R 5 are 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 , or —SO 2 R 6 ; 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; R 9 is hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkoxy(C 1 -C 4 alkyl)-, cycloalkyl, or fully or partially fluorinated C 1 -C 4 alkyl; R 1 (i) a bond; (ii) a divalent radical of formula —(CH 2 ) a B 1 (CH 2 ) b wherein a and b are independently O, 1, 2 or 3 provided that a+b is 1, 2 or 3, and B 1 is —CO—, —O—, —S—, —SO—, —SO 2 —, —CH 2 —, —CHCH 3 —, —CHOH— or —NR 7 —; or (iii) a divalent radical selected from —C(R 10 )(R 11 )—*, —C(R 10 )(R 11 )—O—*, —C(R 10 )(R 11 )CH 2 —*, —C(R 10 )(R 11 )CH 2 —O—*, —CH 2 C(R 10 )(R 11 )—*, —CH 2 C(R 10 )(R 11 )—O—*, —CH 2 —O—C(R 10 )(R 11 )—* and —C(R 10 )(R 11 )—O—CH 2 —*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; Z is as defined in the specification; R 10 is hydrogen and R 11 is (C 1 -C 3 )alkyl or —OH; or R 10 and R 11 are both (C 1 -C 3 )alkyl; or R 10 and R 11 taken together with the carbon atom to which they are attached form a (C 3 -C 5 )cycloalkyl ring.

  式(I)的化合物抑制CB1受体的正常信号活动，因此可用于治疗由CB1受体信号活动介导的疾病或症状，例如肥胖和超重的治疗，预防体重增加，直接或间接与肥胖和超重相关的疾病和症状的治疗：其中A1是氢，-COOH或四唑基；p和q独立地为0或1；A3是苯基或环烷基，其中任一可选地用R4和/或R5取代；R4和R5独立地为-R9，-CN，-F，-Cl，-Br，-OR9，-NR7R8，-NR7COR6，-NR7SO2R6，-COR6，-SR9，-SOR9或-SO2R6；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为氢，C1-C4烷基，C1-C4烷氧基，C1-C4烷氧基（C1-C4烷基）-，环烷基或完全或部分氟化的C1-C4烷基；R1(i)为键；（ii）为式-（CH2）aB1（CH2）b的二价基团，其中a和b独立地为O，1，2或3，前提是a+b为1，2或3，B1为-CO-，-O-，-S-，-SO-，-SO2-，-CH2-，-CHCH3-，-CHOH-或-NR7-；或（iii）为从-C（R10）（R11）- *，-C（R10）（R11）-O- *，-C（R10）（R11）CH2- *，-C（R10）（R11）CH2- O- *，-CH2C（R10）（R11）- *，-CH2C（R10）（R11）-O- *，-CH2-O-C（R10）（R11）- *和-C（R10）（R11）-O-CH2- *中选择的二价基团，其中由星号表示的键连接到吡唑环；Z如规范中所定义；R10为氢，R11为（C1-C3）烷基或-OH；或R10和R11均为（C1-C3）烷基；或R10和R11与它们连接的碳原子一起形成（C3-C5）环烷基环。
• MODULATORS OF CB1 RECEPTORS
  申请人：7TM Pharma A/S

  公开号：EP2121659B1

  公开（公告）日：2013-05-15
• US8148404B2
  申请人：——

  公开号：US8148404B2

  公开（公告）日：2012-04-03
• [EN] MODULATORS OF CB1 RECEPTORS<br/>[FR] MODULATEURS DE RÉCEPTEURS CB1
  申请人：7TM PHARMA AS

  公开号：WO2008075019A1

  公开（公告）日：2008-06-26

  [EN] Compounds of formula (I) suppress the normal signalling activity CB1 receptors, and are thus useful in the treatment of diseases or conditions which are mediated by CB1 receptor signalling activity, such as treatment of obesity and overweight, prevention of weigh gain, treatment of diseases and conditions directly or indirectly associated with obesity and overweight: wherein A₁ is hydrogen, -COOH, or tetrazolyl; p and q are independently 0 or 1; A3 is phenyl or cycloalkyl, either of which is optionally substituted with R₄ and/or R₅; R₄ and R₅ are independently -R₉, -CN, -F, -Cl, -Br, -OR₉, -NR₇R₈, -NR₇COR₆, -NR₇SO₂R₆, -COR₆, -SR₉, -SOR₉, or -SO₂R₆; R₆ is C₁-C₄ alkyl, cycloalkyl, -CF₃ or -NR₇R₈; R₇ and R₈ are independently hydrogen, C₁-C₄ alkyl or cycloalkyl; R₉ is hydrogen, C₁-C₄ alkyl, C₁- C₄ alkoxy, C₁-C₄ alkoxy(C₁-C₄ alkyl)-, cycloalkyl, or fully or partially fluorinated C₁-C₄ alkyl; R₁ (i) a bond; (ii) a divalent radical of formula -(CH₂)_aB₁(CH₂)_b wherein a and b are independently O, 1, 2 or 3 provided that a+b is 1, 2 or 3, and B₁ is -CO-, -0-, -S-, -SO-, - SO₂-, -CH₂-, -CHCH₃-, -CHOH- or -NR₇-; or (iii) a divalent radical selected from - C(R₁₀)(R₁₁)-*, -C(R₁₀)(R₁₁)-O-*, -C(R₁₀)(R₁₁)CH₂-*, -C(R₁₀)(R₁₁)CH₂-O-*, -CH₂C(R₁₀)(R₁₁)-*, -CH₂C(R₁₀)(R₁₁)-O-*, -CH₂-O-C(R₁₀)(R₁₁)-* and -C(R₁₀)(R₁₁)-O-CH₂-*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; Z is as defined in the specification; R₁₀ is hydrogen and R₁₁ is (C₁-C₃)alkyl or -OH; or R₁₀ and R₁₁ are both (C₁-C₃)alkyl; or R₁₀ and R₁₁ taken together with the carbon atom to which they are attached form a (C₃-C₅)cycloalkyl ring.
  [FR] L'invention concerne des composés de formule (I) supprimant l'activité de signalisation normale des récepteurs CB1, et utilisées dans le traitement de maladies ou de troubles induits par ladite activité, notamment dans le traitement de l'obésité et du surpoids, dans la prévention de prise de poids, dans le traitement de maladies et de troubles directement ou indirectement associés à l'obésité et au surpoids. Dans cette formule, A₁ représente un hydrogène, -COOH, ou un tétrazolyle; p et q représentent de façon indépendante 0 ou 1; A₃ représente un phényle ou un cycloalkyle, chacun d'eux pouvant être substitués par R₄ et/ou R₅; R₄ et R₅ représentent de façon indépendante -R₉, -CN, -F, -Cl, -Br, -OR₉, -NR₇R₈, -NR₇COR₆, -NR₇SO₂R₆, -COR₆, -SR₉, -SOR₉, ou -SO₂R₆; R₆ représente un alkyle ou un cycloalkyle en C₁-C₄, -CF₃ ou -NR₇R₈; R₇ et R₈ représentent de façon indépendante un hydrogène, un alkyle ou un cycloalkyle en C₁-C4; R₉ représente un hydrogène, un alkyle en C₁-C₄, un alcoxy en C₁- C₄, un alcoxy en C₁-C₄ (alkyle en C₁-C₄)-, cycloalkyle, ou un alkyle en C₁-C₄ entièrement ou partiellement fluoré; R₁ (i) une liaison; (ii) un radical divalent de formule -(CH₂)_aB₁(CH₂)_b dans laquelle a et b représentent de façon indépendante 0, 1, 2 ou 3, à condition que a+b valent 1, 2 ou 3, et B₁ représente -CO-, -O-, -S-, -SO-, - SO₂-, -CH₂-, -CHCH₃-, -CHOH- ou -NR₇-; ou (iii) un radical divalent sélectionné parmi - C(R₁₀)(R₁₁)-*, -C(R₁₀)(R₁₁)-O-*, -C(R₁₀)(R₁₁)CH₂-*, -C(R₁₀)(R₁₁)CH₂-O-*, -CH₂C(R₁₀)(R₁₁)-*, -CH₂C(R₁₀)(R₁₁)-O-*, -CH₂-O-C(R₁₀)(R₁₁)-* et -C(R₁₀)(R₁₁)-O-CH₂-*, la liaison indiquée par une astérisque étant liée au cycle pyrazole; Z est tel que défini dans le descriptif; R₁₀ représente un hydrogène et R₁₁ un alkyle en (C₁-C₃) ou -OH; ou R₁₀ et R₁₁ représentent tous les deux un alkyle en (C₁-C₃); ou R₁₀ et R₁₁ forment avec l'atome de carbone auquel ils sont liés un cycle cycloalkyle en (C₃-C₅).
• 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.