tert-butyl 4-(4,5-dimethyl-1,3-thiazol-2-yl)-1-piperazinecarboxylate | 675149-74-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(4,5-dimethyl-1,3-thiazol-2-yl)-1-piperazinecarboxylate
• 英文别名: Tert-butyl 4-(4,5-dimethyl-1,3-thiazol-2-yl)piperazine-1-carboxylate
• CAS: 675149-74-3
• 化学式: C₁₄H₂₃N₃O₂S
• 分子量: 297.422
• InChiKey: WFAYYBMHWZASBO-UHFFFAOYSA-N

物化性质

• 沸点：
  417.1±55.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  73.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4,5-dimethyl-1,3-thiazol-2-yl)-1-piperazinecarboxylate 生成 1-(4,5-二甲基-2-噻唑)-哌嗪
  参考文献：
  名称：

  Isosteric replacements for benzothiazoles and optimisation to potent Cathepsin K inhibitors free from hERG channel inhibition

  摘要：

  The discovery of nitrile compound 4, a potent inhibitor of Cathepsin K (Cat K) with good bioavailability in dog is described. The compound was used to demonstrate target engagement and inhibition of Cat K in an in vivo dog PD model. The margin to hERG ion channel inhibition was deemed too low for a clinical candidate and an optimisation program to find isosteres or substitutions on benzothiazole group led to the discovery of 20, 24 and 27; all three free from hERG inhibition. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.012
• 作为产物：
  描述：

  3-氯-2-丁酮 、 4-Boc-哌嗪-1-硫酰胺 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 17.0h， 以22%的产率得到tert-butyl 4-(4,5-dimethyl-1,3-thiazol-2-yl)-1-piperazinecarboxylate
  参考文献：
  名称：

  Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group

  摘要：

  A series of (4 beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl) piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.031

文献信息

• FIVE-MEMBERED HETEROCYCLIC COMPOUNDS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1541564A1

  公开（公告）日：2005-06-15

  The present invention provides a compound represented by the formula: wherein R1 is an optionally substituted 5-membered heterocyclic group; X, Y and V are the same or different and each is a bond, an oxygen atom, a sulfur atom and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is -(CH2)n-Z1- or -Z1-(CH2)n- (n is an integer of 0 to 8, Z1 is a bond, an oxygen atom, a sulfur atom and the like); ring B is a nitrogen-containing heterocycle optionally further having 1 to 3 substituents; W is a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; R2 is a hydrogen atom, a cyano group, -PO(OR9)(OR10) (R9 and R10 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, and R9 and R10 are optionally bonded to form an optionally substituted ring) and the like, or a salt thereof, which has a superior adipose tissue weight decreasing action, a hypoglycemic action and a hypolipidemic action, and which is useful as an agent for the prophylaxis or treatment of obesity, diabetes mellitus, hyperlipidemia, impaired glucose tolerance, hypertension and the like.

  本发明提供了一种由以下式表示的化合物： 其中R1是可选择地取代的5-成员杂环基团；X、Y和V相同或不同，每个都是键，氧原子，硫原子等；Q是具有1到20个碳原子的二价碳氢基团；环A是一个芳香环，可选择地进一步具有1到3个取代基；Z是-(CH2)n-Z1-或-Z1-( )n-（n是0到8的整数，Z1是键，氧原子，硫原子等）；环B是一个含氮杂环，可选择地进一步具有1到3个取代基；W是键或具有1到20个碳原子的二价碳氢基团；R2是氢原子，氰基，-PO(OR9)(OR10)（R9和R10相同或不同，每个是氢原子或可选择地取代的碳氢基团，R9和R10可选择地结合形成可选择地取代的环）等，或其盐，具有优越的减少脂肪组织重量的作用，降糖作用和降脂作用，并且作为预防或治疗肥胖症，糖尿病，高脂血症，糖耐量受损，高血压等的药剂是有用的。
• Five-membered heterocyclic compounds
  申请人：Momose Yu

  公开号：US20060135578A1

  公开（公告）日：2006-06-22

  The present invention provides a compound represented by the formula: wherein R 1 is an optionally substituted 5-membered heterocyclic group; X, Y and V are the same or different and each is a bond, an oxygen atom, a sulfur atom and the like; Q is a divalent hydrocarbon group having 1 to 20 carbon atoms; ring A is an aromatic ring optionally further having 1 to 3 substituents; Z is —(CH 2 ) n -Z 1 - or -Z 1 -(CH 2 ) n — (n is an integer of 0 to 8, Z 1 is a bond, an oxygen atom, a sulfur atom and the like); ring B is a nitrogen-containing heterocycle optionally further having 1 to 3 substituents; W is a bond or a divalent hydrocarbon group having 1 to 20 carbon atoms; R 2 is a hydrogen atom, a cyano group, —PO(OR 9 )(OR 10 ) (R 9 and R 10 are the same or different and each is a hydrogen atom or an optionally substituted hydrocarbon group, and R 9 and R 10 are optionally bonded to form an optionally substituted ring) and the like, or a salt thereof, which has a superior adipose tissue weight decreasing action, a hypoglycemic action and a hypolipidemic action, and which is useful as an agent for the prophylaxis or treatment of obesity, diabetes mellitus, hyperlipidemia, impaired glucose tolerance, hypertension and the like.

  本发明提供一种化合物，其化学式表示为：其中，R1为可选取的取代的5-成员杂环基；X、Y和V相同或不同，每个都是键，氧原子，硫原子等；Q为具有1到20个碳原子的二价碳氢基团；环A为芳香环，可选地进一步具有1到3个取代基；Z为—(CH2)n-Z1-或-Z1-( )n—（n为0到8的整数，Z1为键，氧原子，硫原子等）；环B为含氮杂环，可选地进一步具有1到3个取代基；W为键或具有1到20个碳原子的二价碳氢基团；R2为氢原子，氰基，—PO(OR9)(OR10)（R9和R10相同或不同，每个都是氢原子或可选取的取代的碳氢基团，R9和R10可选择性地结合形成可选取的取代环）等，或其盐，具有优异的减轻脂肪组织重量、降血糖和降血脂作用，可用作预防或治疗肥胖症、糖尿病、高脂血症、糖耐量受损、高血压等的药剂。
• US7368578B2
  申请人：——

  公开号：US7368578B2

  公开（公告）日：2008-05-06