5-(4-chloro-phenyl)-1-(2-chloro-phenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid [1-(4-bromo-phenyl)-ethyl]-amide | 1034265-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-chloro-phenyl)-1-(2-chloro-phenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid [1-(4-bromo-phenyl)-ethyl]-amide
• 英文别名: N-[1-(4-bromophenyl)ethyl]-1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-(cyanomethyl)pyrazole-3-carboxamide
• CAS: 1034265-68-3
• 化学式: C₂₆H₁₉BrCl₂N₄O
• 分子量: 554.273
• InChiKey: SFXPPTXTJWFHHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  5-(4-chloro-phenyl)-1-(2-chloro-phenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid [1-(4-bromo-phenyl)-ethyl]-amide 在 sodium azide 、 盐酸二甲胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以35%的产率得到1-(2-chloro-phenyl)-5-(4-chloro-phenyl)-4-(1H-tetrazol-5-ylmethyl)-1H-pyrazole-3-carboxylic acid [1-(4-bromo-phenyl)-ethyl]-amide
  参考文献：
  名称：

  WO2008/75012

  摘要：

  公开号：
• 作为产物：
  描述：

  5-(4-chlorophenyl)-1-(2-chlorophenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid 、 4-溴-α-甲基苄胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.25h， 以88%的产率得到5-(4-chloro-phenyl)-1-(2-chloro-phenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid [1-(4-bromo-phenyl)-ethyl]-amide
  参考文献：
  名称：

  WO2008/75012

  摘要：

  公开号：

文献信息

• CB1 RECEPTOR MODULATORS
  申请人：Cooper Martin

  公开号：US20100010061A1

  公开（公告）日：2010-01-14

  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, and A 2 is hydrogen, —COOH, or tetrazolyl, 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 3 is hydrogen, C 1 -C 4 alkyl, cycloalkyl, —CF 3 , or —OR 9 ; 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 , 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, —CF 3 , or cycloalkyl; R 9 is hydrogen, C 1 -C 4 alkyl, cycloalkyl, fully or partially fluorinated C 1 -C 4 alkyl; R 1 is (i) a bond, or (ii) —(CH 2 ) a B 1 (CH 2 ) b — wherein a and b are independently 0, 1, 2 or 3 provided that a+b is 1, 2 or 3; or (iii) —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 )—* or —C(R 10 )(R 11 )—O—CH 2 —*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; R 2 is a divalent radical of formula -Q 1 -A 4 -[Q 2 ] w - wherein Q1, A4 Q2 and w are as defined in the specification; and 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，因此在治疗由CB1受体信号活动介导的疾病或病症方面有用，例如治疗肥胖和超重，预防体重增加，直接或间接与肥胖和超重相关的疾病和病症的治疗：其中A1是氢，-COOH或四唑基，A2是氢，-COOH或四唑基，但A1和A2中的一个是-COOH或四唑基；p为0或1，A3是苯基或环烷基，其中任一种都可以被R4和/或R5取代；q为0或1；R3是氢，C1-C4烷基，环烷基，-CF3或-OR9；R4和R5独立地是-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独立地是氢，C1-C4烷基，-CF3或环烷基；R9是氢，C1-C4烷基，环烷基，完全或部分氟化的C1-C4烷基；R1是（i）键，或（ii）-（CH2）aB1（CH2）b-，其中a和b独立地为0、1、2或3，但a+b为1、2或3；或（iii）-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）- *或-C（R10）（R11）-O-CH2- *，其中星号表示连接到吡唑环的键；R2是式-Q1-A4-[Q2]w-的二价基团，其中Q1，A4，Q2和w在规范中定义；R10是氢，R11是（C1-C3）烷基或-OH；或R10和R11都是（C1-C3）烷基；或R10和R11与它们所连接的碳原子一起形成（C3-C5）环烷基环。
• CB1 receptor modulators
  申请人：7TM Pharma A/S

  公开号：US08124634B2

  公开（公告）日：2012-02-28

  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, and A2 is hydrogen, —COOH, or tetrazolyl, provided that one of A1 and A2 is either —COOH or tetrazolyl; p is 0 or 1 and A3 is phenyl or cycloalkyl, either of which is optionally substituted with R4 and/or R5; q is 0 or 1; R3 is hydrogen, C1-C4 alkyl, cycloalkyl, —CF3, or —OR9; R4 and R5 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, —CF3, or cycloalkyl; R9 is hydrogen, C1-C4 alkyl, cycloalkyl, fully or partially fluorinated C1-C4 alkyl; R1 is (i) a bond, or (ii) —(CH2)aB1(CH2)b— wherein a and b are independently 0, 1, 2 or 3 provided that a+b is 1, 2 or 3; or (iii) —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)—* or —C(R10)(R11)—O—CH2—*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; R2 is a divalent radical of formula -Q1-A4-[Q2]w- wherein Q1, A4 Q2 and w are as defined in the specification; and 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.

  化合物的公式（I）抑制CB1受体的正常信号活性，因此可用于治疗由CB1受体信号活性介导的疾病或病况，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病况的治疗。其中A1是氢、—COOH或四唑基，A2是氢、—COOH或四唑基，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，其中任一可选地取代R4和/或R5；q为0或1；R3为氢、C1-C4烷基、环烷基、—CF3或—OR9；R4和R5独立地为—R9、—CN、—F、—Cl、—Br、—OR9、—NR7R8、—NR7COR6、—NR7SO2R6、—COR6、—SR9、—SOR9或—SO2R6；R6为C1-C4烷基、环烷基、—CF3或—NR7R8；R7和R8独立地为氢、C1-C4烷基、—CF3或环烷基；R9为氢、C1-C4烷基、环烷基、完全或部分氟代的C1-C4烷基；R1为(i)键，或(ii) —(CH2)aB1(CH2)b—，其中a和b独立地为0、1、2或3，前提是a+b为1、2或3；或(iii) —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)—*或—C(R10)(R11)—O—CH2—*，其中星号表示连接到吡唑环的键；R2为公式-Q1-A4-[Q2]w-的二价基团，其中Q1、A4、Q2和w在说明书中定义；R10为氢，R11为（C1-C3）烷基或—OH；或R10和R11都为（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。
• US8124634B2
  申请人：——

  公开号：US8124634B2

  公开（公告）日：2012-02-28
• [EN] CB1 RECEPTOR MODULATORS<br/>[FR] MODULATEURS DE RÉCEPTEUR CB1
  申请人：7TM PHARMA AS

  公开号：WO2008075012A1

  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, and A₂ is hydrogen, -COOH, or tetrazolyl, 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; R₃ is hydrogen, C₁-C₄ alkyl, cycloalkyi, -CF₃, or -OR₉; R₄ and R₅ 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, -CF₃, or cycloaikyL R₉ is hydrogen, C₁-C₄ alkyl, cycloalkyl, fully or partially fluorinated C₁-C₄ alkyl; R₁ is (i) a bond, or (ii) -(CH₂)_aB₁(CH₂)_b- wherein a and b are independently O, 1, 2 or 3 provided that a+b is 1, 2 or 3; or (iii) -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)-* or -C(R₁₀)(R₁₁)-O-CH₂-*, wherein the bond indicated by an asterisk is attached to the pyrazole ring; R2 is a divalent radical of formula -Q₁A₄-[Q₂]w- wherein Q₁, A₄, Q₂ and w are as defined in the specification; and 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 qui sont utiles dans le traitement de maladies ou de troubles induits par l'activité de signalisation du récepteur CB1, 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 et A₂ représentent un hydrogène, -COOH, ou un tétrazolyle, à condition que l'un de A₁ et A₂ représente soit -COOH, soit un tétrazolyle; p prend la valeur de 0 ou 1 et A₃ représente un phényle ou un cycloalkyle, chacun d'eux pouvant être substitué par R₄ et/ou R₅; q prend la valeur de 0 ou 1; R₃ représente un hydrogène, un alkyle ou un cycloalkyle en C₁-C_4, -CF₃ ou -OR₉; 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-C_4, -CF₃ ou -NR₇R₈; R₇ et R₈ représentent de façon indépendante un hydrogène, un alkyle en C₁-C_4, -CF₃ ou un cycloalkyle; R₉ représente un hydrogène, un alkyle ou un cycloalkyle en C₁-C₄, un alkyle en C₁-C₄ entièrement ou partiellement fluoré; R₁ représente (i) une liaison, ou (ii) --(CH₂)_aB₁(CH₂)_b-, a et b représentant de façon indépendante 0, 1, 2 ou 3 à condition que a+b vale 1, 2 ou 3, ou (iii) -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)-* or -C(R₁₀)(R₁₁)-O-CH₂-*, la liaison indiquée par une astérisque étant liée au cycle pyrazole; R₂ représente un radical divalent de formule -Q₁A₄-[Q₂]w-, Q₁, A₄, Q₂ et w étant tels que définis dans la description; et 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).
• WO2008/75012
  申请人：——

  公开号：——

  公开（公告）日：——