(5-{[({5-butyl-1-[5-methyl-4-(2-thienyl)pyrimidin-2-yl]-1H-pyrazol-4-yl}carbonyl)amino]methyl}-1H-imidazol-1-yl)acetic acid | 1019255-74-3

• 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
• 英文名称: (5-{[({5-butyl-1-[5-methyl-4-(2-thienyl)pyrimidin-2-yl]-1H-pyrazol-4-yl}carbonyl)amino]methyl}-1H-imidazol-1-yl)acetic acid
• 英文别名: 2-[5-[[[5-Butyl-1-(5-methyl-4-thiophen-2-ylpyrimidin-2-yl)pyrazole-4-carbonyl]amino]methyl]imidazol-1-yl]acetic acid
• CAS: 1019255-74-3
• 化学式: C₂₃H₂₅N₇O₃S
• 分子量: 479.563
• InChiKey: PSBCZUNMLKUTRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氯-5-甲基-4-(噻吩-2-基)嘧啶 在 吡啶 、 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 N,N-二异丙基乙胺 、 lithium hydroxide 、 肼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 (5-{[({5-butyl-1-[5-methyl-4-(2-thienyl)pyrimidin-2-yl]-1H-pyrazol-4-yl}carbonyl)amino]methyl}-1H-imidazol-1-yl)acetic acid
  参考文献：
  名称：

  Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes

  摘要：

  GPR142 is a G protein-coupled receptor that is predominantly expressed in pancreatic beta-cells. GPR142 agonists stimulate insulin secretion in the presence of high glucose concentration, so that they could be novel insulin secretagogues with reduced or no risk of hypoglycemia. We report here the optimization of HTS hit compound 1 toward a proof of concept compound 33, which showed potent glucose lowering effects during an oral glucose tolerance test in mice and monkeys.

  DOI：

  10.1021/ml400186z

文献信息

• N-aryl pyrazole compounds, compositions, and methods for their use
  申请人：Ogawa Yasuyuki

  公开号：US20080153778A1

  公开（公告）日：2008-06-26

  Compounds having formula I: where A 1 , A 2 , L, V, W, R 1 , R 2 , R 3 , R 4 and R 5 are as described herein, compositions thereof, and their use for the treatment or prevention of type 2 diabetes and type 2 diabetes-related conditions are provided herein.

  本文提供化学式为I的化合物，其中A1、A2、L、V、W、R1、R2、R3、R4和R5如本文所述，以及其组合物，并用于治疗或预防2型糖尿病和2型糖尿病相关疾病。
• N-ARYL PYRAZOLE COMPOUNDS FOR USE AGAINST DIABETES
  申请人：Amgen Inc.

  公开号：EP2079728A1

  公开（公告）日：2009-07-22
• US8022061B2
  申请人：——

  公开号：US8022061B2

  公开（公告）日：2011-09-20
• [EN] N-ARYL PYRAZOLE COMPOUNDS FOR USE AGAINST DIABETES<br/>[FR] COMPOSÉS DE N-ARYLPYRAZOLE À UTILISER CONTRE LE DIABÈTE
  申请人：AMGEN INC

  公开号：WO2008045484A1

  公开（公告）日：2008-04-17

  [EN] Compounds having formula I:where A¹, A², L, V, W, R¹, R², R³, R⁴ and R⁵ are as described herein, compositions thereof, and their use for the treatment or prevention of type 2 diabetes and type 2 diabetes-related conditions are provided herein.
  [FR] L'invention concerne des composés de formule I, dans laquelle A¹, A², L, V, W, R¹, R², R³, R⁴ et R⁵ ont la signification indiquée dans la description, des compositions de ceux-ci, et leur utilisation pour le traitement ou la prévention du diabète de type 2 et d'états associés au diabète de type 2.
• Potent and Orally Bioavailable GPR142 Agonists as Novel Insulin Secretagogues for the Treatment of Type 2 Diabetes
  作者：Narihiro Toda、Xiaolin Hao、Yasuyuki Ogawa、Kozo Oda、Ming Yu、Zice Fu、Yi Chen、Yongjae Kim、Mike Lizarzaburu、Sarah Lively、Shauna Lawlis、Michiko Murakoshi、Futoshi Nara、Nobuaki Watanabe、Jeff D. Reagan、Hui Tian、Angela Fu、Alykhan Motani、Qingxiang Liu、Yi-Jyun Lin、Run Zhuang、Yumei Xiong、Peter Fan、Julio Medina、Leping Li、Masanori Izumi、Ryo Okuyama、Satoshi Shibuya

  DOI：10.1021/ml400186z

  日期：2013.8.8

  GPR142 is a G protein-coupled receptor that is predominantly expressed in pancreatic beta-cells. GPR142 agonists stimulate insulin secretion in the presence of high glucose concentration, so that they could be novel insulin secretagogues with reduced or no risk of hypoglycemia. We report here the optimization of HTS hit compound 1 toward a proof of concept compound 33, which showed potent glucose lowering effects during an oral glucose tolerance test in mice and monkeys.