N-[3,5-(bistrifluoromethyl)phenyl]-N'-cyano-O-phenylisourea | 250262-04-5

• 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: N-[3,5-(bistrifluoromethyl)phenyl]-N'-cyano-O-phenylisourea
• 英文别名: N-(3,5-bis(trifluoromethyl)phenyl)-N'-cyano-O-phenylisourea；phenyl N'-[3,5-bis(trifluoromethyl)phenyl]-N-cyanocarbamimidate
• CAS: 250262-04-5
• 化学式: C₁₆H₉F₆N₃O
• 分子量: 373.257
• InChiKey: NVIMVBZOIXJVST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  57.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[3,5-(bistrifluoromethyl)phenyl]-N'-cyano-O-phenylisourea 在 正丙胺 作用下， 以 二氯甲烷 为溶剂， 以28%的产率得到
  参考文献：
  名称：

  Substituted guanidines and diaminonitroethenes, their preparation and use

  摘要：

  该公式代表的胍和二氨基硝基乙烯衍生物，其中X，R.sup.1，R.sup.2，R.sup.3和R.sup.4在描述中有定义，描述了它们的组成以及制备这些化合物的方法。这些化合物在治疗中枢神经系统、心血管系统、肺部系统、消化系统和内分泌系统疾病中具有用途。

  公开号：

  US06147098A1
• 作为产物：
  描述：

  N-氰基羰亚胺二苯基酯 、 间二(三氟甲基)苯胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以73.6%的产率得到N-[3,5-(bistrifluoromethyl)phenyl]-N'-cyano-O-phenylisourea
  参考文献：
  名称：

  Arylcyanoguanidines as Activators of Kir6.2/SUR1K_ATP Channels and Inhibitors of Insulin Release

  摘要：

  Phenylcyanoguanidines substituted with lipophilic electron-withdrawing functional groups, e.g. N-cyano-N'-[3,5-bis-(trifluoromethyl)phenyl]-N"-(cyclopentyl)guanidine (10) and N-cyano-N'-(3,5-dichlorophenyl)-N"-(3-methylbutyl)guanidine (12) were synthesized and investigated for their ability to inhibit insulin release from beta cells, to repolarize beta cell membrane potential, and to relax precontracted rat aorta rings. Structural modifications gave compounds, which selectively inhibit insulin release from betaTC6 cells (e.g. compound 10: IC50 = 5.45 +/- 1.9 muM) and which repolarize betaTC3 beta cells (10: IC50 = 4.7 +/- 0.5 muM) without relaxation of precontracted aorta rings (10: IC50 > 300 muM). Inhibition of insulin release from rat islets was observed in the same concentration level as for betaTC6 cells (10: IC50 = 1.24 +/- 0.1 muM, 12: IC50 = 3.8 +/- 0.4 muM). Compound 10 (10 muM) inhibits calcium outflow and insulin release from perifused rat pancreatic islets. The mechanisms of action of 10 and 12 were further investigated. The compounds depolarize mitochondrial membrane from smooth muscle cells and beta cell and stimulate glucose utilization and mitochondrial respiration in isolated liver cells. Furthermore, 10 was studied in a patch clamp experiment and was found to activate Kir6.2/SUR1 and inhibit Kir6.2/SUR2B type of K-ATP channels. These studies indicate that the observed effects of the compounds on beta cells result from activation of K-ATP channels of the cell membrane in combination with a depolarization of mitochondrial membranes. It also highlights that small structural changes can dramatically shift the efficacy of the cyanoguanidine type of selective activators of Mr6.2/SUR2 potassium channels.

  DOI：

  10.1021/jm031018y

文献信息

• [EN] SUBSTITUTED GUANIDINES AND DIAMINONITROETHENES, THEIR PREPARATION AND USE<br/>[FR] GUANIDINES ET DIAMINONITROETHENES SUBSTITUEES, PREPARATION ET APPLICATIONS
  申请人：NOVO NORDISK A/S

  公开号：WO1999058497A1

  公开（公告）日：1999-11-18

  (EN) Guanidine and diaminonitroethene derivatives represented by formula (I), wherein X, R1, R2, R3 and R4 are defined in the description, compositions thereof and methods for preparing the compounds described. The compounds are useful in the treatment of diseases of central nervous system, the cardiovascular system, pulmonary system, the gastrointestinal system and the endocrinological system.(FR) Cette invention, qui a trait à des dérivés de guanidine et de diaminonitroéthène correspondant à la formule (I), X, R1, R2, R3 et R4 étant définis dans le descriptif, concerne également des compositions à base de ces substances ainsi que des procédés de préparation des composés décrits. Ces composés s'avèrent des plus utiles en matière de traitement de maladies du système nerveux central, du système cardio-vasculaire, du système pulmonaire, de l'appareil digestif et du système endocrinien.

  (中文) 本发明涉及公式(I)所代表的鸟氨酸和二氨基硝基乙烯衍生物，其中X、R1、R2、R3和R4在说明书中有定义，以及这些化合物的组合物和制备方法。这些化合物对于治疗中枢神经系统、心血管系统、肺系统、胃肠系统和内分泌系统的疾病非常有用。
• Phenylcyanoguanidines as inhibitors of glucose-induced insulin secretion from beta cells
  作者：Tina M Tagmose、John P Mogensen、Pia C Agerholm、Per O.G Arkhammar、Philip Wahl、Anne Worsaae、J.Bondo Hansen

  DOI：10.1016/s0960-894x(01)00297-9

  日期：2001.7

  3.5-Disubstituted-phenylcyanoguanidines have been identified as activators of SUR1/Kir6.2 potassium channels and as potent inhibitors of insulin release from pancreatic beta cells in vitro. (C) 2001 Elsevier Science Ltd. All rights reserved.
• SUBSTITUTED GUANIDINES AND DIAMINONITROETHENES, THEIR PREPARATION AND USE
  申请人：NOVO NORDISK A/S

  公开号：EP1077933A1

  公开（公告）日：2001-02-28
• US6147098A
  申请人：——

  公开号：US6147098A

  公开（公告）日：2000-11-14