denagliptin tosylate | 811432-66-3

• 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: denagliptin tosylate
• 英文别名: (2S,4S)-4-fluoro-1-[4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]-2-pyrrolidinecarbonitrile；(2S,4S)-1-[(2S)-2-amino-3,3-bis(4-fluorophenyl)propanoyl]-4-fluoropyrrolidine-2-carbonitrile;4-methylbenzenesulfonic acid
• CAS: 811432-66-3
• 化学式: C₇H₈O₃S*C₂₀H₁₈F₃N₃O
• 分子量: 545.582
• InChiKey: MSCWUTTUQLYJFT-QMBKNIKNSA-N

物化性质

• 熔点：
  241-245 °C (decomp)(Solv: isopropanol (67-63-0); water (7732-18-5))

计算性质

• 辛醇/水分配系数(LogP)：
  4.13
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  tert-butyl {(1S)-1-[bis(4-fluorophenyl)methyl]-2-[(2S)-cyano-(4S)-fluoro-1-pyrrolidinyl]-2-oxoethyl}carbamate 、 对甲苯磺酸 在 异丙醇 作用下， 反应 7.0h， 以91.9 kg的产率得到denagliptin tosylate
  参考文献：
  名称：

  大规模合成甲苯磺酸登格列汀的进展

  摘要：

  已经开发了甲苯磺酸登格列汀的大规模合成。通过改变步骤顺序（在后期进行脱水），从最初的规模化路线中提高了合成效率。合成的关键步骤是由正丙膦酸环酐介导的单步肽偶联/脱水。描述了将这种合成方法发展为稳健而实用的制造路线所面临的挑战。

  DOI：

  10.1021/op900178d

文献信息

• [EN] (2S,4S)-4-FLUORO-1-[4-FLUORO-BETA-(4-FLUOROPHENYL)-L-PHENYLALANYL]-2-PYRROLIDINECARBONITRILE P-TOLUENESULFONIC ACID SALT AND ANHYDROUS CRYSTALLINE FORMS THEREOF<br/>[FR] SEL D'ACIDE (2S,4S)-4-FLUORO-1-[4-FLUORO-BETA-(4-FLUOROPHENYL)-1-PHENYLALANYL]-2-PYRROLIDINECARBONITRILE P-TOLUENESULFONIQUE, ET CERTAINES DE SES FORMES CRRISTALLINES ANHYDRES
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005009956A1

  公开（公告）日：2005-02-03

  The present invention includes anhydrous crystalline forms of (2S,4S)-4-fluoro-1-[4-fluoro-beta-(4-fluorophenyl)-L-phenylalanyl]-2-pyrrolidinecarbonitrile p-toluenesulfonic acid salt.

  本发明包括(2S,4S)-4-氟-1-[4-氟-β-(4-氟苯基)-L-苯丙氨基]-2-吡咯烷碳腈对甲苯磺酸盐的无水结晶形式。
• (2S,4s)-4-fluoro-1-[4-fluoro-beta-(4-fluorophenyl)-I-phenylalanyl]-2-pyrrolidinecarbonitrile p-toluenesulfonic acid salt and anhydrous crystalline forms thereof
  申请人：Igo H David

  公开号：US20070066677A1

  公开（公告）日：2007-03-22

  The present invention includes anhydrous crystalline forms of (2S,4S)-4-fluoro-1-[4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]-2-pyrrolidinecarbonitrile p-toluenesulfonic acid salt.

  本发明涉及(2S,4S)-4-氟-1-[4-氟-β-(4-氟苯基)-L-苯丙氨基]-2-吡咯烷基氰酸盐的无水晶型态，其为对甲苯磺酸盐。
• (2S,4S)-4-fluoro-1-[4-fluoro-beta-(4-fluorophenyl)-L-phenylalanyl]-2-pyrrolidinecarbonitrile p-toluenesulfonic acid salt and anhydrous crystalline forms thereof
  申请人：SmithKline Beecham Corporation

  公开号：US07462641B2

  公开（公告）日：2008-12-09

  The present invention includes anhydrous crystalline forms of (2S,4S)-4-fluoro-1-[4-fluoro-β-(4-fluorophenyl)-L-phenylalanyl]-2-pyrrolidinecarbonitrile p-toluenesulfonic acid salt.

  本发明涉及(2S,4S)-4-氟-1-[4-氟-β-(4-氟苯基)-L-苯丙氨基]-2-吡咯烷羧腈对甲苯磺酸盐的无水晶体形式。
• MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO
  申请人：Jones Robert M.

  公开号：US20130023494A1

  公开（公告）日：2013-01-24

  The present invention relates to compounds of Formula (Ia) and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as a single agent or in combination with one or more additional pharmaceutical agents, such as, an inhibitor of DPP-IV, a biguanide, an SGLT2 inhibitor, or an alpha-glucosidase inhibitor, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing a blood incretin level; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

  本发明涉及式(Ia)化合物及其药学上可接受的盐、溶剂和水合物，可作为单一药剂或与一种或多种其他药物剂合用，例如DPP-IV抑制剂、双胍类药物、SGLT2抑制剂或α-葡萄糖苷酶抑制剂，用于治疗选择自：GPR119受体相关疾病；通过增加血液肠促素水平改善的状况；代谢相关疾病；2型糖尿病；肥胖症；以及相关并发症的障碍。
• Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
  申请人：Jones Robert M.

  公开号：US20140038889A1

  公开（公告）日：2014-02-06

  The present invention relates to the GPR119 agonist, 1-methylcyclopropyl 4-(5-fluoro-6-(2-methyl-6-(methylsulfonyl)pyridin-3-yloxy)pyrimidin-4-yloxy)piperidine-1-carboxylate (Compound 1): and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as single pharmaceutical agents 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 the 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激动剂，1-甲基环丙基4-(5-氟-6-(2-甲基-6-(甲基磺酰基)吡啶-3-氧基)嘧啶-4-氧基)哌啶-1-羧酸甲酯（化合物1）及其药学上可接受的盐、溶剂合物和水合物，它们可作为单一药物或与一个或多个其他药物联合使用，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、噻唑烷二酮或抗糖尿病肽类似物，用于治疗例如GPR119受体相关疾病；通过增加肠促素分泌改善的病症；通过增加血液肠促素水平改善的病症；低骨密度症状；神经系统疾病；代谢相关疾病；2型糖尿病；肥胖症及相关并发症。