2-((1r,4r)-4-(1-methylpiperidin-4-yloxy)cyclohexyloxy)-5-(methylsulfonyl)pyrazine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-((1r,4r)-4-(1-methylpiperidin-4-yloxy)cyclohexyloxy)-5-(methylsulfonyl)pyrazine
• 英文别名: 2-[4-(1-Methylpiperidin-4-yl)oxycyclohexyl]oxy-5-methylsulfonylpyrazine；2-[4-(1-methylpiperidin-4-yl)oxycyclohexyl]oxy-5-methylsulfonylpyrazine
• 化学式: C₁₇H₂₇N₃O₄S
• 分子量: 369.485
• InChiKey: KUUVVJVCDLFWPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  90
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-((1r,4r)-4-(1-methylpiperidin-4-yloxy)cyclohexyloxy)-5-(methylsulfonyl)pyrazine 在 N,N-二异丙基乙胺 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 3-isopropyl-5-(4-((1r,4r)-4-(5-(methylsulfonyl)pyrazin-2-yloxy)cyclohexyloxy)piperidin-1-yl)-1,2,4-oxadiazole
  参考文献：
  名称：

  [EN] MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO
  [FR] MODULATEURS DU RÉCEPTEUR DE GPR119 ET TRAITEMENT DE TROUBLES ASSOCIÉS

  摘要：

  本发明涉及式(Ia)的化合物及其药学上可接受的盐、溶剂和水合物，这些化合物可作为单一药剂或与一个或多个额外的药剂（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）结合使用，在治疗中发挥作用，例如治疗选择自：GPR119受体相关疾病；通过增加血液胰高血糖素水平改善的病症；与代谢相关的疾病；2型糖尿病；肥胖；以及相关并发症。

  公开号：

  WO2011127051A1
• 作为产物：
  描述：

  4-氯吡啶 在 盐酸 、 sodium tetrahydroborate 、 copper(I) trifluoromethanesulfonate benzene 、 potassium tert-butylate 、 N,N-二甲基乙二胺 、 sodium t-butanolate 作用下， 生成 2-((1r,4r)-4-(1-methylpiperidin-4-yloxy)cyclohexyloxy)-5-(methylsulfonyl)pyrazine
  参考文献：
  名称：

  Discovery of a novel trans-1,4-dioxycyclohexane GPR119 agonist series

  摘要：

  The design and optimization of a novel trans-1,4-dioxycyclohexane GPR119 agonist series is described. A lead compound 21 was found to be a potent and efficacious GPR119 agonist across species, and possessed overall favorable pharmaceutical properties. Compound 21 demonstrated robust acute and chronic regulatory effects on glycemic parameters in the diabetic or non-diabetic rodent models. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.102

文献信息

• 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。
• [EN] MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR DE GPR119 ET TRAITEMENT DE TROUBLES ASSOCIÉS
  申请人：ARENA PHARM INC

  公开号：WO2011127051A1

  公开（公告）日：2011-10-13

  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 pharmacetical 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)的化合物及其药学上可接受的盐、溶剂和水合物，这些化合物可作为单一药剂或与一个或多个额外的药剂（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）结合使用，在治疗中发挥作用，例如治疗选择自：GPR119受体相关疾病；通过增加血液胰高血糖素水平改善的病症；与代谢相关的疾病；2型糖尿病；肥胖；以及相关并发症。
• Discovery of a novel trans-1,4-dioxycyclohexane GPR119 agonist series
  作者：Sangdon Han、Sanju Narayanan、Sun Hee Kim、Imelda Calderon、Xiuwen Zhu、Andrew Kawasaki、Dawei Yue、Juerg Lehmann、Amy Wong、Daniel J. Buzard、Graeme Semple、Chris Carroll、Zhi-Liang Chu、Hussein Al-Sharmma、Hsin-Hui Shu、Shiu-Feng Tung、David J. Unett、Dominic P. Behan、Woo Hyun Yoon、Michael Morgan、Khawja A. Usmani、Chuan Chen、Abu Sadeque、James N. Leonard、Robert M. Jones

  DOI：10.1016/j.bmcl.2015.04.102

  日期：2015.8

  The design and optimization of a novel trans-1,4-dioxycyclohexane GPR119 agonist series is described. A lead compound 21 was found to be a potent and efficacious GPR119 agonist across species, and possessed overall favorable pharmaceutical properties. Compound 21 demonstrated robust acute and chronic regulatory effects on glycemic parameters in the diabetic or non-diabetic rodent models. (C) 2015 Elsevier Ltd. All rights reserved.