N-({4-[3-(trifluoromethyl)benzenesulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide | 1362155-28-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-({4-[3-(trifluoromethyl)benzenesulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide
• 英文别名: N-[[4-[3-(trifluoromethyl)phenyl]sulfonylphenyl]methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide
• CAS: 1362155-28-9
• 化学式: C₂₂H₁₆F₃N₃O₃S
• 分子量: 459.449
• InChiKey: ZLBUBPJKDMSFHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氮杂吲哚-2-甲酸 、 (4-((3-(trifluoromethyl)phenyl)sulfonyl)phenyl)methanamine 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.42h， 以25%的产率得到N-({4-[3-(trifluoromethyl)benzenesulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Structure-Based Discovery of Novel Amide-Containing Nicotinamide Phosphoribosyltransferase (Nampt) Inhibitors

  摘要：

  Crystal structures of several urea- and thiourea-derived compounds in complex with the nicotinamide phosphoribosyltransferase (Nampt) protein were utilized to design a potent amide-containing inhibitor bearing an aza-indole moiety (7, Nampt BC IC50 = 9.0 nM, A2780 cell proliferation IC50 = 10 nM). The Nampt-7 cocrystal structure was subsequently obtained and enabled the design of additional amide-containing inhibitors which incorporated various other fused 6,5-heterocyclic moieties and biaryl sulfone or sulfonamide motifs. Additional modifications of these molecules afforded many potent biaryl sulfone-containing Nampt inhibitors which also exhibited favorable in vitro ADME properties (microsomal and hepatocyte stability, MOCK permeability, plasma protein binding). An optimized compound (58) was a potent inhibitor of multiple cancer cell lines (IC50 <10 nM vs U251, HT1080, PC3, MiaPaCa2, and HCT116 lines), displayed acceptable mouse PK properties (F = 41%, CL = 52.4 mL/min/kg), and exhibited robust efficacy in a U251 mouse xenograft model.

  DOI：

  10.1021/jm4008664

文献信息

• [EN] MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR GPR119 ET TRAITEMENT DES TROUBLES QUI LUI SONT LIÉS
  申请人：ARENA PHARM INC

  公开号：WO2012040279A1

  公开（公告）日：2012-03-29

  The present invention relates to the GPR119 receptor agonists:3-fluoro-4-(5-fluoro-6-(4-(3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)-N,N-dimethylbenzamide; -fluoro-4-(5-fluoro-6-(4-(3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)-N-methylbenzamide; and 3-fluoro-4-(5-fluoro-6-(4-(3-(2-fluoropropan-2-yl)-1,2,4-oxadiazol-5-yl)piperidin-1-yl)pyrimidin-4-ylamino)benzamide, and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as a single pharmaceutical agent or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

  本发明涉及GPR119受体激动剂：3-氟-4-(5-氟-6-(4-(3-(2-氟丙基)-1,2,4-噁二唑-5-基)哌啶-1-基)嘧啶-4-基氨基)-N,N-二甲基苯甲酰胺；-氟-4-(5-氟-6-(4-(3-(2-氟丙基)-1,2,4-噁二唑-5-基)哌啶-1-基)嘧啶-4-基氨基)-N-甲基苯甲酰胺；以及3-氟-4-(5-氟-6-(4-(3-(2-氟丙基)-1,2,4-噁二唑-5-基)哌啶-1-基)嘧啶-4-基氨基)苯甲酰胺，以及其药学上可接受的盐、溶剂化合物和水合物，这些化合物可用作单一药物代理或与一个或多个额外的药物代理结合使用，例如DPP-IV抑制剂、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素类似物、磺脲类药物、SGLT2抑制剂、噻唑烷二酮类药物或抗糖尿病肽类似物，用于治疗例如从以下选择的疾病：GPR119受体相关疾病；通过增加胰高血糖素分泌而改善的疾病；通过增加血液中胰高血糖素水平而改善的疾病；低骨密度症状；神经系统疾病；代谢相关疾病；2型糖尿病；肥胖症；以及相关并发症的治疗。
• [EN] MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR GPR119 ET TRAITEMENT DE TROUBLES ASSOCIÉS
  申请人：ARENA PHARM INC

  公开号：WO2013055910A1

  公开（公告）日：2013-04-18

  The present invention relates to compounds of Formula (I) and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof,that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, an inhibitor of DPP-IV, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

  本发明涉及式(I)的化合物及其药学上可接受的盐、溶剂化合物、水合物和N-氧化物，这些化合物可作为单一药物代理或与一个或多个额外的药物代理结合使用，例如DPP-IV的抑制剂、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素类似物、磺脲类药物、SGLT2抑制剂、噻嗪二酮类药物或抗糖尿病肽类似物，用于治疗例如从以下选择的疾病中选择的疾病：GPR119受体相关疾病；通过增加促胰高血糖素分泌而改善的状况；通过增加血液促胰高血糖素水平而改善的状况；低骨量状况；神经系统疾病；与代谢相关的疾病；2型糖尿病；肥胖症；以及相关并发症。
• [EN] SALTS OF LORCASERIN WITH OPTICALLY ACTIVE ACIDS<br/>[FR] SELS DE LORCASÉRINE DOTÉS D'ACIDES OPTIQUEMENT ACTIFS
  申请人：ARENA PHARM INC

  公开号：WO2012030938A1

  公开（公告）日：2012-03-08

  Salts of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine with optically active acids, and pharmaceutical compositions comprising them that are useful for, inter alia, weight management.

  含有光学活性酸的8-氯-1-甲基-2,3,4,5-四氢-1H-3-苯并哌啶盐，以及包括它们的药物组合物，可用于诸如体重管理等用途。
• [EN] FAST-DISSOLVE DOSAGE FORMS OF 5-HT2C AGONISTS<br/>[FR] FORMES POSOLOGIQUES À DISSOLUTION RAPIDE D'AGONISTES DE 5-HT2C
  申请人：ARENA PHARM INC

  公开号：WO2012030951A1

  公开（公告）日：2012-03-08

  Salts of the 5-HT2C-receptor agonist (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine, and dosage forms comprising them that are useful for, inter alia, weight management.

  ( R ) -8-氯-1-甲基-2,3,4,5-四氢-1H-3-苯并哌啶的5-HT2C受体激动剂盐，以及包含它们的剂型，可用于体重管理等用途。
• [EN] NOVEL COMPOUNDS AND COMPOSITIONS FOR THE INHIBITION OF NAMPT<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITIONS POUR L'INHIBITION DE NAMPT
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2012031197A1

  公开（公告）日：2012-03-08

  The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

  本发明涉及用于抑制NAMPT的化合物和组合物，以及它们的合成、应用和解毒剂。本发明的一个示例化合物如下所示：