1-(5-([1,4'-bipiperidin]-1'-yl)-1,3,4-thiadiazol-2-yl)-3-(pyridin-2-yl)piperidin-3-ol | 1350900-56-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(5-([1,4'-bipiperidin]-1'-yl)-1,3,4-thiadiazol-2-yl)-3-(pyridin-2-yl)piperidin-3-ol
• 英文别名: 1-[5-(4-Piperidin-1-ylpiperidin-1-yl)-1,3,4-thiadiazol-2-yl]-3-pyridin-2-ylpiperidin-3-ol
• CAS: 1350900-56-9
• 化学式: C₂₂H₃₂N₆OS
• 分子量: 428.602
• InChiKey: GJPYKVNDRRCAEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  96.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-bromo-5-(4-piperidinopiperidino)-1,3,4-thiadiazole 、 3-(Pyridin-2-yl)piperidin-3-ol 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 三氟甲苯 为溶剂， 反应 3.0h， 生成 1-(5-([1,4'-bipiperidin]-1'-yl)-1,3,4-thiadiazol-2-yl)-3-(pyridin-2-yl)piperidin-3-ol
  参考文献：
  名称：

  Discovery of a Potent Thiadiazole Class of Histamine H₃ Receptor Antagonist for the Treatment of Diabetes

  摘要：

  A series of novel 2-piperidinopiperidine thiadiazoles were synthesized and evaluated as new leads of histamine H-3 receptor antagonists. The 4-(5-([1,4'-bipiperidin]-1'-yl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)morpholine (5u) displayed excellent potency and ex vivo receptor occupancy. Compound 5u was also evaluated in vivo for antidiabetic efficacy in STZ diet-induced obesity type 2 diabetic mice for 2 or 12 days. Non-fasting glucose levels were significantly reduced as compared with vehicle-treated mice. In addition, 5u dose dependently blocked the increase of HbA(1c) after 12 days of treatment.

  DOI：

  10.1021/ml200250t

文献信息

• Discovery of a Potent Thiadiazole Class of Histamine H₃ Receptor Antagonist for the Treatment of Diabetes
  作者：Ashwin U. Rao、Ning Shao、Robert G. Aslanian、Tin-Yau Chan、Sylvia J. Degrado、Li Wang、Brian McKittrick、Mary Senior、Robert E. West、Shirley M. Williams、Ren-Long Wu、Joyce Hwa、Bhuneshwari Patel、Shuqin Zheng、Christopher Sondey、Anandan Palani

  DOI：10.1021/ml200250t

  日期：2012.3.8

  A series of novel 2-piperidinopiperidine thiadiazoles were synthesized and evaluated as new leads of histamine H-3 receptor antagonists. The 4-(5-([1,4'-bipiperidin]-1'-yl)-1,3,4-thiadiazol-2-yl)-2-(pyridin-2-yl)morpholine (5u) displayed excellent potency and ex vivo receptor occupancy. Compound 5u was also evaluated in vivo for antidiabetic efficacy in STZ diet-induced obesity type 2 diabetic mice for 2 or 12 days. Non-fasting glucose levels were significantly reduced as compared with vehicle-treated mice. In addition, 5u dose dependently blocked the increase of HbA(1c) after 12 days of treatment.