2-(4-tert-butylphenyl)-4-[4-(3-fluoro-4-nitrobenzyl)piperazin-1-yl]-1H-benzimidazole | 874279-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(4-tert-butylphenyl)-4-[4-(3-fluoro-4-nitrobenzyl)piperazin-1-yl]-1H-benzimidazole
• 英文别名: 2-(4-tert-butylphenyl)-4-(4-(3-fluoro-4-nitrobenzyl)piperazin-1-yl)-1H-benzo[d]imidazole；2-(4-tert-butyl-phenyl)-4-[4-(3-fluoro-4-nitro-benzyl)-piperazin-1-yl]-1H-benzoimidazole；2-(4-tert-butylphenyl)-4-[4-[(3-fluoro-4-nitrophenyl)methyl]piperazin-1-yl]-1H-benzimidazole
• CAS: 874279-41-1
• 化学式: C₂₈H₃₀FN₅O₂
• 分子量: 487.577
• InChiKey: YZXYFZZILSFLBC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-tert-butylphenyl)-4-[4-(3-fluoro-4-nitrobenzyl)piperazin-1-yl]-1H-benzimidazole 在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 生成 4-[4-(3-azido-4-nitrobenzyl)piperazin-1-yl]-2-(4-tert-butylphenyl)-1H-benzimidazole
  参考文献：
  名称：

  2-Phenyl-4-piperazinylbenzimidazoles: Orally active inhibitors of the gonadotropin releasing hormone (GnRH) receptor

  摘要：

  Antagonism of the gonadotropin releasing hormone (GnRH) receptor has shown positive clinical results in numerous reproductive tissue disorders such as endometriosis, prostate cancer and others. Traditional therapy has been limited to peptide agonists and antagonists. Recently, small molecule GnRH antagonists have emerged as potentially new treatments. This article describes the discovery of 2-phenyl-4-piperazinylbenzimidazoles as small molecule GnRH antagonists with nanomolar potency in in vitro binding and functional assays, excellent bioavailability (rat % F > 70) and demonstrated oral activity in a rat model having shown significant serum leuteinizing hormone (LH) suppression. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.024
• 作为产物：
  描述：

  2-(4-tert-butylphenyl)-4-(piperazin-1-yl)-1H-benzo[d]imidazole 、 3-氟-4-硝基苯甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 生成 2-(4-tert-butylphenyl)-4-[4-(3-fluoro-4-nitrobenzyl)piperazin-1-yl]-1H-benzimidazole
  参考文献：
  名称：

  2-Phenyl-4-piperazinylbenzimidazoles: Orally active inhibitors of the gonadotropin releasing hormone (GnRH) receptor

  摘要：

  Antagonism of the gonadotropin releasing hormone (GnRH) receptor has shown positive clinical results in numerous reproductive tissue disorders such as endometriosis, prostate cancer and others. Traditional therapy has been limited to peptide agonists and antagonists. Recently, small molecule GnRH antagonists have emerged as potentially new treatments. This article describes the discovery of 2-phenyl-4-piperazinylbenzimidazoles as small molecule GnRH antagonists with nanomolar potency in in vitro binding and functional assays, excellent bioavailability (rat % F > 70) and demonstrated oral activity in a rat model having shown significant serum leuteinizing hormone (LH) suppression. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.024

文献信息

• Gonadotropin releasing hormone receptor antagonists
  申请人：Garrick Michael Lloyd

  公开号：US20060019965A1

  公开（公告）日：2006-01-26

  The present invention relates to Gonadotropin Releasing Hormone (“GnRH”) (also known as Leutinizing Hormone Releasing Hormone) receptor antagonists.

  本发明涉及促性腺激素释放激素（“GnRH”）（也称为促黄体生成激素释放激素）受体拮抗剂。
• Discovery of 6-({4-[2-(4-<i>tert</i>-Butylphenyl)-1<i>H</i>-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024): An Orally Active Antagonist of the Gonadotropin Releasing Hormone Receptor (GnRH-R)
  作者：Jeffrey C. Pelletier、Murty V. Chengalvala、Joshua E. Cottom、Irene B. Feingold、Daniel M. Green、Diane B. Hauze、Christine A. Huselton、James W. Jetter、Gregory S. Kopf、Joseph T. Lundquist、Ronald L. Magolda、Charles W. Mann、John F. Mehlmann、John F. Rogers、Linda K. Shanno、William R. Adams、Cesario O. Tio、Jay E. Wrobel

  DOI：10.1021/jm801572m

  日期：2009.4.9

  A potent, highly insoluble, GnRH antagonist with a 2-phenyl-4-piperazinylbenzimidazole template and a quinoxaline-2,3-dione pharmacophore was modified to maintain GnRH antagonist activity and improve in vitro pharmaceutical properties. Structural changes to the quinoxaline-2,3-dione portion of the molecule resulted in several structures with improved properties and culminated in the discovery of 6-((4-[2-(4-tertbutylphenyl)-1H-benzimidazol-4-yl]piperazin-1-yl}methyl)quinoxaline (WAY-207024). The compound was shown to have excellent pharmacokinetic parameters and lowered rat plasma LH levels after oral administration.
• GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS
  申请人：Wyeth

  公开号：EP1758895A1

  公开（公告）日：2007-03-07
• US7696210B2
  申请人：——

  公开号：US7696210B2

  公开（公告）日：2010-04-13
• [EN] GONADOTROPIN RELEASING HORMONE RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEURS DE L'HORMONE DE LIBÉRATION DE GONADOTROPHINES
  申请人：WYETH CORP

  公开号：WO2006009734A1

  公开（公告）日：2006-01-26

  The present invention relates to Gonadotropin Releasing Hormone (“GnRH”) (also known as Leutinizing Hormone Releasing Hormone) receptor antagonists.