trans-5-methylene-3-nitro-2-(2,5-difluorophenyl)-tetrahydro-2H-pyran

• 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: trans-5-methylene-3-nitro-2-(2,5-difluorophenyl)-tetrahydro-2H-pyran
• 英文别名: trans-2-(2,5-difluorophenyl)-5-methylene-3-nitrotetrahydro-2H-pyran；(2S,3R)-2-(2,5-difluorophenyl)-5-methylidene-3-nitrooxane
• 化学式: C₁₂H₁₁F₂NO₃
• 分子量: 255.221
• InChiKey: VEHIHEPLGDQYLG-NEPJUHHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-5-methylene-3-nitro-2-(2,5-difluorophenyl)-tetrahydro-2H-pyran 在 sodium periodate 、 四氧化锇 、 硫酸 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 锌 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 水 为溶剂， 反应 43.5h， 生成 奥格列汀
  参考文献：
  名称：

  Omarigliptin (MK-3102): A Novel Long-Acting DPP-4 Inhibitor for Once-Weekly Treatment of Type 2 Diabetes

  摘要：

  In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.

  DOI：

  10.1021/jm401992e
• 作为产物：
  描述：

  2,5-二氟苯甲酰氯 在 sodium tetrahydroborate 、 sodium hydride 、 N,N-二异丙基乙胺 作用下， 生成 trans-5-methylene-3-nitro-2-(2,5-difluorophenyl)-tetrahydro-2H-pyran
  参考文献：
  名称：

  Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: Profile of clinical candidate (2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-amine (23)

  摘要：

  A series of novel tri-2,3,5-substituted tetrahydropyran analogs were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). Compound 23, which is very potent, selective, efficacious in the diabetes PD model, and has an excellent pharmacokinetic profile, is selected as a clinical candidate. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.061

文献信息

• [EN] 2-PHENYL-5-HETEROCYCLYL-TETRAHYDRO-2H-PYRAN-3-AMINE COMPOUNDS FOR USE IN THE TREATMENT OF DIABETES AND ITS ASSOCIATED DISORDERS<br/>[FR] COMPOSÉS DE 2-PHÉNYL-5-HÉTÉROCYCLYL-TÉTRAHYDRO-2H-PYRAN-3-AMINE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DU DIABÈTE ET DE SES TROUBLES ASSOCIÉS
  申请人：CADILA HEALTHCARE LTD

  公开号：WO2014061031A1

  公开（公告）日：2014-04-24

  The present invention relates to novel compounds of the general formula (I) their tautomeric forms, their enantiomers, their diastereoisomers, their pharmaceutically accepted salts, or pro-drugs thereof, which are useful for the treatment or prevention of diabetes mellitus (DM), obesity and other metabolic disorders. The invention also relates to process for the manufacture of said compounds, and pharmaceutical compositions containing them and their use.

  本发明涉及一般式(I)的新化合物，其互变异构体形式、其对映体、其二对映异构体、其药学上可接受的盐或其前药，用于治疗或预防糖尿病（DM）、肥胖和其他代谢紊乱。该发明还涉及制备所述化合物的方法，以及含有它们的药物组合物及其用途。
• 2-PHENYL-5-HETEROCYCLYL-TETRAHYDRO-2H-PYRAN-3-AMINE COMPOUNDS FOR USE IN THE TREATMENT OF DIABETES AND ITS ASSOCIATED DISORDERS
  申请人：CADILA HEALTHCARE LIMITED

  公开号：US20150246025A1

  公开（公告）日：2015-09-03

  The present invention relates to novel compounds of the general formula (I) their tautomeric forms, their enantiomers, their diastereoisomers, their pharmaceutically accepted salts, or pro-drugs thereof, which are useful for the treatment or prevention of diabetes mellitus (DM), obesity and other metabolic disorders. The invention also relates to process for the manufacture of said compounds, and pharmaceutical compositions containing them and their use.

  本发明涉及一种新颖的化合物，其通式为（I），其互变异构体形式，其对映异构体，其顺反异构体，其药学上可接受的盐或前药，用于治疗或预防糖尿病（DM），肥胖症和其他代谢性疾病。本发明还涉及制备所述化合物的方法，以及包含它们的药物组合物和它们的用途。
• EP2909199A1
  申请人：——

  公开号：EP2909199A1

  公开（公告）日：2015-08-26
• Novel tetrahydropyran analogs as dipeptidyl peptidase IV inhibitors: Profile of clinical candidate (2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-amine (23)
  作者：Tesfaye Biftu、Xiaoxia Qian、Ping Chen、Dennis Feng、Giovanna Scapin、Ying-Duo Gao、Jason Cox、Ranabir Sinha Roy、George Eiermann、Huabing He、Kathy Lyons、Gino Salituro、Sangita Patel、Alexander Petrov、Feng Xu、Shiyao Sherrie Xu、Bei Zhang、Charles Caldwell、Joseph K. Wu、Kathy Lyons、Ann E. Weber

  DOI：10.1016/j.bmcl.2013.07.061

  日期：2013.10

  A series of novel tri-2,3,5-substituted tetrahydropyran analogs were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the series provided inhibitors with good DPP-4 potency and selectivity over other peptidases (QPP, DPP8, and FAP). Compound 23, which is very potent, selective, efficacious in the diabetes PD model, and has an excellent pharmacokinetic profile, is selected as a clinical candidate. (C) 2013 Elsevier Ltd. All rights reserved.
• Omarigliptin (MK-3102): A Novel Long-Acting DPP-4 Inhibitor for Once-Weekly Treatment of Type 2 Diabetes
  作者：Tesfaye Biftu、Ranabir Sinha-Roy、Ping Chen、Xiaoxia Qian、Dennis Feng、Jeffrey T. Kuethe、Giovanna Scapin、Ying Duo Gao、Youwei Yan、Davida Krueger、Annette Bak、George Eiermann、Jiafang He、Jason Cox、Jacqueline Hicks、Kathy Lyons、Huaibing He、Gino Salituro、Sharon Tong、Sangita Patel、George Doss、Aleksandr Petrov、Joseph Wu、Shiyao Sherrie Xu、Charles Sewall、Xiaoping Zhang、Bei Zhang、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1021/jm401992e

  日期：2014.4.24

  In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development.