diphenyl(1H-1,2,3-triazol-4-yl)methanol | 50561-44-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diphenyl(1H-1,2,3-triazol-4-yl)methanol
• 英文别名: 4-(hydroxydiphenylmethyl)-1H-1,2,3-triazole；diphenyl(2H-triazol-4-yl)methanol
• CAS: 50561-44-9
• 化学式: C₁₅H₁₃N₃O
• 分子量: 251.288
• InChiKey: DOAAXYCBZJDQRJ-UHFFFAOYSA-N

物化性质

• 沸点：
  478.3±40.0 °C(Predicted)
• 密度：
  1.288±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  三光气 、 diphenyl(1H-1,2,3-triazol-4-yl)methanol 、 2-((4-fluorophenoxy)methyl)piperidine 在 N,N-二异丙基乙胺 、 4-二甲氨基吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以20%的产率得到(2-((4-fluorophenoxy)methyl)piperidin-1-yl)(4-(hydroxydiphenylmethyl)-2H-1,2,3-triazol-2-yl)methanone
  参考文献：
  名称：

  Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

  摘要：

  Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2 -AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4 -substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5 -position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting -induced refeeding of mice, thereby emulating the effect of cannabinoid' CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

  DOI：

  10.1021/acs.jmedchem.6b01482
• 作为产物：
  描述：

  二苯甲酮 在 copper(l) iodide 、 正丁基锂 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 diphenyl(1H-1,2,3-triazol-4-yl)methanol
  参考文献：
  名称：

  Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding

  摘要：

  Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported that triazole ureas can act as selective and CNS-active inhibitors for diacylglycerol lipases (DAGLs), enzymes responsible for the biosynthesis of 2-arachidonoylglycerol (2 -AG) that activates cannabinoid CB1 receptor. Here, we report the enantio- and diastereoselective synthesis and structure-activity relationship studies. We found that 2,4 -substituted triazole ureas with a biphenylmethanol group provided the most optimal scaffold. Introduction of a chiral ether substituent on the 5 -position of the piperidine ring provided ultrapotent inhibitor 38 (DH376) with picomolar activity. Compound 38 temporarily reduces fasting -induced refeeding of mice, thereby emulating the effect of cannabinoid' CB1-receptor inverse agonists. This was mirrored by 39 (DO34) but also by the negative control compound 40 (DO53) (which does not inhibit DAGL), which indicates the triazole ureas may affect the energy balance in mice through multiple molecular targets.

  DOI：

  10.1021/acs.jmedchem.6b01482

文献信息

• [FR] INHIBITEURS DES SÉRINE HYDROLASES DE TYPE N1- ET N2-CARBAMOYL-1,2,3-TRIAZOLE ET MÉTHODES ASSOCIÉES
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2012138877A1

  公开（公告）日：2012-10-11

  The present invention provides inhibitors of a wide variety of serine hydrolase enzymes. The inhibitors of the present invention are N1- and N2-carbamoyl-1,2,3-triazole compounds such as those of Formula (I): (Formula (I)) in which N1, N2 and N3 are the nitrogen atoms at positions 1, 2, and 3, respectively, of the triazole ring, and R4, R5, R6, and R7 in Formula (I) are as described herein. Methods of inhibiting serine hydrolase enzymes and methods of preparing carbamoyl-1,2,3-triazole compounds also are described.

  本发明提供了多种丝氨酸水解酶的抑制剂。本发明的抑制剂是N1-和N2-羰胺基-1,2,3-三唑化合物，如式（I）所示：（式（I）），其中N1、N2和N3分别为三唑环的1、2和3位置的氮原子，式（I）中的R4、R5、R6和R7如本文所述。还描述了抑制丝氨酸水解酶酶和制备羰胺基-1,2,3-三唑化合物的方法。
• N1- and N2-CARBAMOYL-1,2,3-TRIAZOLE SERINE HYDROLASE INHIBITORS AND METHODS
  申请人：Cravatt Benjamin

  公开号：US20140018318A1

  公开（公告）日：2014-01-16

  The present invention provides inhibitors of a wide variety of serine hydrolase enzymes. The inhibitors of the present invention are N1- and N2-carbamoyl-1,2,3-triazole compounds such as those of Formula (I): in which N1, N2, and N3 are the nitrogen atoms at positions 1, 2, and 3, respectively, of the triazole ring, and R 4 , R 5 , R 6 and R 7 in Formula (I) are as described herein. Methods of inhibiting serine hydrolase enzymes and methods of preparing carbamoyl-1,2,3-triazole compounds also are described.

  本发明提供了一种广泛的丝氨酸水解酶酶抑制剂。本发明的抑制剂是N1-和N2-氨基甲酰基-1,2,3-三唑化合物，例如公式（I）中的化合物：其中N1、N2和N3是三唑环的1、2和3位置的氮原子，公式（I）中的R4、R5、R6和R7如本文所述。还描述了抑制丝氨酸水解酶的方法和制备氨基甲酰基-1,2,3-三唑化合物的方法。
• IMIDAZOLE DERIVATIVES
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：EP0110996B1

  公开（公告）日：1986-09-03
• SULFUR-HETEROCYCLE EXCHANGE CHEMISTRY AND USES THEREOF
  申请人：University of Virginia Patent Foundation

  公开号：US20220214355A1

  公开（公告）日：2022-07-07

  Sulfonyl-triazole compounds and related sulfonyl-heterocycle compounds are described. The compounds can be used to identify reactive nucleophilic amino acid residues, such as reactive tyrosines and reactive lysines, in proteins and to modify the activity of proteins with reactive nucleophilic amino acid residues via the formation of protein adducts comprising a fragment of the compounds. Methods are also described for screening the compounds to identify ligands of proteins comprising a reactive lysine or a reactive tyrosine.
• US9108930B2
  申请人：——

  公开号：US9108930B2

  公开（公告）日：2015-08-18