1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-methyl-1H-pyrrole-3-carboxylic acid | 723303-33-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-methyl-1H-pyrrole-3-carboxylic acid
• 英文别名: 1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-methyl-1H-pyrrol-3-carboxylic acid；1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-methylpyrrole-3-carboxylic acid
• CAS: 723303-33-1
• 化学式: C₁₈H₁₂Cl₃NO₂
• 分子量: 380.658
• InChiKey: NMQKEPWIZQBWPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-methyl-1H-pyrrole-3-carboxylic acid 在 N,N'-羰基二咪唑 、 氨 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-methyl-1H-pyrrol-3-carboxamide
  参考文献：
  名称：

  1,5-DIARYLPYRROLE DERIVATIVES, PREPARATION METHOD THEREOF AND APPLICATION OF SAME IN THERAPEUTICS

  摘要：

  该发明涉及具有以下结构式（I）的化合物：其中X，R1，R2，R3，R4，R5和R6如本文所定义。该发明还涉及一种制备所述化合物的方法以及在治疗中的应用。

  公开号：

  US20080015245A1
• 作为产物：
  描述：

  ethyl 1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-methyl-1H-pyrrole-3-carboxylate 在 sodium hydroxide 、 水 、 potassium carbonate 、 盐酸 作用下， 以 乙醇 、 乙酸乙酯 、 水 为溶剂， 反应 24.0h， 生成 1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-2-methyl-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  1,5-DIARYLPYRROLE DERIVATIVES, PREPARATION METHOD THEREOF AND APPLICATION OF SAME IN THERAPEUTICS

  摘要：

  该发明涉及具有以下结构式（I）的化合物：其中X，R1，R2，R3，R4，R5和R6如本文所定义。该发明还涉及一种制备所述化合物的方法以及在治疗中的应用。

  公开号：

  US20080015245A1

文献信息

• [EN] 1,5-DIARYL-PYRROLE-3-CARBOXAMIDE DERIVATIVES AND THEIR USE AS CANNABINOID RECEPTOR MODULATORS<br/>[FR] DERIVES DE 1,5-DIARYL-PYRROLE-3-CARBOXAMIDE ET LEUR UTILISATION EN TANT QUE MODULATEURS DES RECEPTEURS DES CANNABINOIDES
  申请人：ASTRAZENECA AB

  公开号：WO2004058249A1

  公开（公告）日：2004-07-15

  The present invention relates to a compound of formula (I) (A chemical formula should be inserted here - please see paper copy enclosed herewith) in which R1 and R2 independently represent phenyl, thienyl or pyridyl each of which is optionally substituted by one, two or three groups represented by Z; and R3 is H, a C1-3alkyl group, a C1-3alkoxymethyl group, trifluoromethyl, a hydroxyC1-3alkyl group, an aminoC1-3alkyl group, C1-3alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C1-3alkylcarbamoyl, acetyl, or hydrazinocarbonyl of formula -CONHNRaRb wherein Ra and Rb are as defined for R4 and R5 respectively; X is CO or SO2 ; Y is absent or represents NH optionally substituted by a C1-3alkyl group; R4 and R5 independently represent: a C1-6alkyl group; an (amino)C1-4alkyl- group in which the amino is optionally substituted by one or more C1-3alkyl groups; an optionally substituted non-aromatic C3-15carbocyclic group; a (C3-12cycloalkyl)C1-3alkyl- group; a group -(CH2)r(phenyl )s; naphthyl; anthracenyl; a saturated 5 to 8 membered heterocyclic group containing one nitrogen and optionally one of the following: oxygen, sulphur or an additional nitrogen wherein the heterocyclic group is optionally substituted ;1-adamantylmethyl; a group - (CH2)t Het where Het represents an aromatic heterocycle optionally substituted; or R4 represents H and R5 is as defined above; or R4 and R5 together with the nitrogen atom to which they are attached represent a saturated 5 to 8 membered heterocyclic group; R6 is H, a C1-3alkyl group, a C1-3alkoxymethyl group, trifluoromethyl, a hydroxyC1-3alkyl group, C1-3alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C1-3alkylcarbamoyl, acetyl, or hydrazinocarbonyl of formula -CONHNRaRb ; with provisos; to processes for preparing such compounds, to their use in the treatment of obesity, psychiatric and neurological disorders particularly obesity, to methods for their therapeutic use and to pharmaceutical compositions containing them.

  本发明涉及一种化合物，其化学式为（I），其中R1和R2分别独立表示苯基，噻吩基或吡啶基，每个基上均可选择性地取代一个、两个或三个由Z表示的基团；R3为H，C1-3烷基基团，C1-3烷氧甲基基团，三氟甲基，羟基C1-3烷基基团，氨基C1-3烷基基团，C1-3烷氧羰基，羧基，氰基，氨基甲酰基，一级或二级C1-3烷基甲酰基，乙酰基或化学式为-CONHNRaRb的肼基，其中Ra和Rb分别定义为R4和R5；X为CO或SO2；Y为空或表示NH，该氮原子可选择性地取代为C1-3烷基基团；R4和R5独立地表示：C1-6烷基基团；（氨基）C1-4烷基基团，其中氨基可选择性地取代为一个或多个C1-3烷基基团；可选择性取代的非芳香性C3-15碳环基团；（C3-12环烷基）C1-3烷基基团；基团-(CH2)r(苯) s；萘基；蒽基；含有一个氮原子并可选择性地含有以下之一的饱和的5到8个成员的杂环基团：氧，硫或另一个氮原子，其中杂环基团可选择性地取代；1-金刚烷基甲基；基团-(CH2)t Het，其中Het表示可选择性取代的芳香性杂环族；或者R4表示H，R5如上所定义；或者R4和R5与它们连接的氮原子一起表示饱和的5到8个成员的杂环基团；R6为H，C1-3烷基基团，C1-3烷氧甲基基团，三氟甲基，羟基C1-3烷基基团，C1-3烷氧羰基，羧基，氰基，氨基甲酰基，一级或二级C1-3烷基甲酰基，乙酰基或化学式为-CONHNRaRb的肼基；但需注意的是，本发明还涉及制备这种化合物的方法，以及它们在肥胖、精神和神经疾病特别是肥胖的治疗中的应用方法和包含它们的制药组合物。
• [EN] AQUEOUS DISPERSION COMPRISING STABLE NANOPARTICLES OF A WATER-INSOLUBLE PYRROLE CARBOXAMIDE AND EXCIPIENT LIKE MIDDLE CHAIN TRIGLYCERIDES<br/>[FR] DISPERSION AQUEUSE COMPRENANT DES NANOPARTICULES STABLES DE CARBOXAMIDE DE PYRROLE INSOLUBLE DANS L'EAU ET DES TRIGLYCERIDES A CHAINE MOYENNE DU TYPE EXCIPIENT
  申请人：ASTRAZENECA AB

  公开号：WO2004069227A1

  公开（公告）日：2004-08-19

  A process for the preparation of a stable dispersion of solid particles, in an aqueous medium comprising combining (a) a first solution comprising a substantially water-insoluble substance which is a pyrrole carboxamide compound of Formula I, a water-miscible organic solvent and an inhibitor with (b) an aqueous phase comprising water and optionally a stabiliser, thereby precipitating solid particles comprising the inhibitor and the substantially water-insoluble substance; and optionally removing the water-miscible organic solvent; wherein the inhibitor is a non-polymeric hydrophobic organic compound as defined in the description. Also claimed are stable dispersions obtainable by the process, solid particles obtainable by the process and use of such particles. The process provides a dispersion of solid particles in an aqueous medium, which particles exhibit reduced or substantially no particle growth mediated by Ostwald ripening. The process is particlularly suitable for the preparation of small (sub-micron) aqueous dispersions of a substantially water-insoluble pharmacologically active substance.

  一种制备固体颗粒在水性介质中的稳定分散体的方法，包括将（a）包含化学式I的一种基本不溶于水的物质、易溶于水的有机溶剂和抑制剂的第一溶液与（b）包含水和可选稳定剂的水相结合，从而沉淀出包含抑制剂和基本不溶于水的物质的固体颗粒；并可选择性地去除易溶于水的有机溶剂；其中抑制剂是根据说明中定义的非聚合疏水有机化合物。还声明了通过该方法获得的稳定分散体、通过该方法获得的固体颗粒以及使用这种颗粒。该方法提供了固体颗粒在水性介质中的分散体，这些颗粒表现出由奥斯瓦尔德成核引起的减少或基本无颗粒生长。该方法特别适用于制备基本不溶于水的药理活性物质的小（亚微米）水性分散体。
• 1,5-Diaryl-pyrrole-3-carboxamide derivatives and their use as cannabinoid receptor modulators
  申请人：Berggren Ingrid Kristina Anna

  公开号：US20060122230A1

  公开（公告）日：2006-06-08

  The present invention relates to a compound of formula (I) in which R 1 and R 2 independently represent phenyl, thienyl or pyridyl each of which is optionally substituted by one, two or three groups represented by Z; and R 3 is H, a C 1-3 alkyl group, a C 1-3 alkoxymethyl group, trifluoromethyl, a hydroxyC 1-3 alkyl group, an aminoC 1-3 alkyl group, C 1-3 alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C 1-3 alkylcarbamoyl, acetyl, or hydrazinocarbonyl of formula —CONHNR a R b wherein R a and R b are as defined for R 4 and R 5 respectively; X is CO or SO 2 ; Y is absent or represents NH optionally substituted by a C 1-3 alkyl group; R 4 and R 5 independently represent: a C 1-6 alkyl group; an (amino)C 1-4 alkyl-group in which the amino is optionally substituted by one or more C 1-3 alkyl groups; an optionally substituted non-aromatic C 3-15 carbocyclic group; a (C 3-12 cycloalkyl)C 1-3 alkyl-group; a group —(CH 2 ) r (phenyl) s ; naphthyl; anthracenyl; a saturated 5 to 8 membered heterocyclic group containing one nitrogen and optionally one of the following: oxygen, sulphur or an additional nitrogen wherein the heterocyclic group is optionally substituted; 1-adamantylmethyl; a group —(CH 2 ) t Het where Het represents an aromatic heterocycle optionally substituted; or R 4 represents H and R 5 is as defined above; or R 4 and R 5 together with the nitrogen atom to which they are attached represent a saturated 5 to 8 membered heterocyclic group; R 6 is H, a C 1-3 alkyl group, a C 1-3 alkoxymethyl group, trifluoromethyl, a hydroxyC 1-3 alkyl group, C 1-3 alkoxycarbonyl, carboxy, cyano, carbamoyl, mono or di C 1-3 alkylcarbamoyl, acetyl, or hydrazinocarbonyl of formula —CONHNR a R b ; with provisos; to processes for preparing such compounds, to their use in the treatment of obesity, psychiatric and neurological disorders particularly obesity, to methods for their therapeutic use and to pharmaceutical compositions containing them.

  本发明涉及一种化合物，其化学式为（I），其中R1和R2分别独立表示苯基，噻吩基或吡啶基，每个基团可选地被Z所代表的一个、两个或三个基团取代；而R3则表示H、C1-3烷基、C1-3烷氧甲基、三氟甲基、羟基C1-3烷基、氨基C1-3烷基、C1-3烷氧羰基、羧基、氰基、氨基甲酰基、一级或二级C1-3烷基甲酰基或肼基羰基，其中Ra和Rb分别如同R4和R5所定义；X为CO或SO2；Y为不存在或代表可选地被C1-3烷基取代的NH；而R4和R5独立地表示：C1-6烷基、（氨基）C1-4烷基，其中氨基可选地被一个或多个C1-3烷基取代，可选地被取代的非芳香性C3-15碳环基，（C3-12环烷基）C1-3烷基，基团—（CH2）r（苯基）s，萘基，蒽基，含有一个氮原子且可选地含有以下一种:氧、硫或另一个氮原子的饱和的5到8个成员杂环基，其中该杂环基可选地被取代；1-金刚烷甲基，基团—（CH2）tHet，其中Het代表可选地被取代的芳香性杂环；或者R4表示H，而R5如同上述所定义；或者R4和R5与它们所连接的氮原子一起表示一个饱和的5到8个成员杂环基；而R6表示H、C1-3烷基、C1-3烷氧甲基、三氟甲基、羟基C1-3烷基、C1-3烷氧羰基、羧基、氰基、氨基甲酰基、一级或二级C1-3烷基甲酰基或肼基羰基，其中Ra和Rb分别如同上述所定义；但需注意以下情况：本发明还涉及制备此类化合物的方法，以及将其用于治疗肥胖症、精神和神经疾病，特别是肥胖症的方法和含有它们的制药组合物。
• Aqueous dispersion comprising stable nanoparticles of a water-insoluble pyrrole carboxamide and excipient like middle chain triglycerides
  申请人：Lindfors Lennart

  公开号：US20060198893A1

  公开（公告）日：2006-09-07

  A process for the preparation of a stable dispersion of solid particles, in an aqueous medium comprising combining (a) a first solution comprising a substantially water-insoluble substance which is a pyrrole carboxamide compound of Formula I, a water-miscible organic solvent and an inhibitor with (b) an aqueous phase comprising water and optionally a stabiliser, thereby precipitating solid particles comprising the inhibitor and the substantially water-insoluble substance; and optionally removing the water-miscible organic solvent; wherein the inhibitor is a non-polymeric hydrophobic organic compound as defined in the description. Also claimed are stable dispersions prepared by the process, solid particles prepared by the process and use of such particles.

  一种制备稳定的固体颗粒分散液的方法，其中该分散液在水介质中，包括将（a）第一溶液与（b）水相结合，从而沉淀出包含抑制剂和基本上不溶于水的Formula I吡咯羧酰胺化合物的固体颗粒。第一溶液包括基本上不溶于水的物质、可溶于水的有机溶剂和抑制剂；水相包括水和可选的稳定剂；可选择去除可溶于水的有机溶剂；其中抑制剂是在描述中定义的非聚合疏水有机化合物。此外，还包括通过该方法制备的稳定分散液、通过该方法制备的固体颗粒以及使用这些颗粒的用途。
• 1,5-DIARYL-PYRROLE-3-CARBOXAMIDE DERIVATIVES AND THEIR USE AS CANNABINOID RECEPTOR MODULATORS
  申请人：AstraZeneca AB

  公开号：EP1578417A1

  公开（公告）日：2005-09-28