| 401566-37-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• CAS: 401566-37-8
• 化学式: C₂₄H₃₃N₅O₄S
• 分子量: 487.623
• InChiKey: VLTCNQKTLCIDCQ-HKUYNNGSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  34.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  82.36
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 作用下， 以 甲醇 为溶剂， 反应 120.0h， 生成 3-{(2S,4S)-4-[4-(benzoxazol-2-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl}thiazolidine trihydrochloride
  参考文献：
  名称：

  Fused bicyclic heteroarylpiperazine-substituted l-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group

  摘要：

  Hypoglycemic agents with a mechanism of depeptidyl peptidase IV (DPP-4) inhibition are suitable for once daily oral dosing. It is difficult to strike a balance between inhibitory activity and duration of action in plasma for inhibitors bearing an electrophilic nitrile group. We explored fused bicyclic heteroarylpiperazine substituted at the gamma-position of the proline structure in the investigation of L-prolylthiazolidines lacking the electrophilic nitrile. Among them, 2-trifluoroquinolyl compound 8g is the most potent, long-lasting DPP-4 inhibitor (IC50 = 0.37 nmol/L) with high selectivity against other related peptidases. X-ray crystal structure determination of 8g indicates that CH-pi interactions generated between the quinolyl ring and the guanidinyl group of Arg358 enhances the DPP-4 inhibitory activity and selectivity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.033
• 作为产物：
  描述：

  (2S,4R)-4-羟基-2-(3-噻唑烷基羰基)-1-吡咯烷羧酸叔丁酯 在 三氧化硫吡啶 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 反应 5.0h， 生成
  参考文献：
  名称：

  Fused bicyclic heteroarylpiperazine-substituted l-prolylthiazolidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group

  摘要：

  Hypoglycemic agents with a mechanism of depeptidyl peptidase IV (DPP-4) inhibition are suitable for once daily oral dosing. It is difficult to strike a balance between inhibitory activity and duration of action in plasma for inhibitors bearing an electrophilic nitrile group. We explored fused bicyclic heteroarylpiperazine substituted at the gamma-position of the proline structure in the investigation of L-prolylthiazolidines lacking the electrophilic nitrile. Among them, 2-trifluoroquinolyl compound 8g is the most potent, long-lasting DPP-4 inhibitor (IC50 = 0.37 nmol/L) with high selectivity against other related peptidases. X-ray crystal structure determination of 8g indicates that CH-pi interactions generated between the quinolyl ring and the guanidinyl group of Arg358 enhances the DPP-4 inhibitory activity and selectivity. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.06.033