4-(piperazin-1-yl)-1-trityl-1H-benzo[d]imidazole | 247083-12-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4-(piperazin-1-yl)-1-trityl-1H-benzo[d]imidazole
• 英文别名: 1-(1-tritylbenzimidazol-4-yl)piperazine；4-Piperazin-1-yl-1-tritylbenzimidazole
• CAS: 247083-12-1
• 化学式: C₃₀H₂₈N₄
• 分子量: 444.579
• InChiKey: IMRJYQQJJPTLSL-UHFFFAOYSA-N

物化性质

• 沸点：
  664.1±65.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(piperazin-1-yl)-1-trityl-1H-benzo[d]imidazole 在 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 27.0h， 生成 2-[4-[4-(benzimidazol-4(7)-yl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole
  参考文献：
  名称：

  Pd(0) Amination of Benzimidazoles as an Efficient Method towards New (Benzimidazolyl)piperazines with High Affinity for the 5-HT1A Receptor

  摘要：

  New (benzimidazolyl)amines have been synthesized from 4- and 6-bromobenzimidazole derivatives via palladium-mediated amination reactions. Among them, (benzimidazol-4(7)-yl)piperazine derivatives have been shown to be a new family of high affinity 5-HT1A receptor ligands. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00225-8
• 作为产物：
  描述：

  4-溴-1H-苯并咪唑 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 四丁基碘化铵 、 sodium hydride 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 5.0h， 生成 4-(piperazin-1-yl)-1-trityl-1H-benzo[d]imidazole
  参考文献：
  名称：

  Pd(0) Amination of Benzimidazoles as an Efficient Method towards New (Benzimidazolyl)piperazines with High Affinity for the 5-HT1A Receptor

  摘要：

  New (benzimidazolyl)amines have been synthesized from 4- and 6-bromobenzimidazole derivatives via palladium-mediated amination reactions. Among them, (benzimidazol-4(7)-yl)piperazine derivatives have been shown to be a new family of high affinity 5-HT1A receptor ligands. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00225-8

文献信息

• Benzimidazole derivatives. Part 5: Design and synthesis of new benzimidazole–arylpiperazine derivatives acting as mixed 5-HT1A/5-HT3 ligands
  作者：María L. López-Rodríguez、Bellinda Benhamú、M José Morcillo、Ignacio Tejada、David Avila、Isabel Marco、Lucio Schiapparelli、Diana Frechilla、Joaquín Del Río

  DOI：10.1016/j.bmc.2004.07.023

  日期：2004.10

  A series of new mixed benzimidazole-arylpiperazine derivatives were designed by incorporating in general structure III the pharmacophoric elements of 5-HT(1A) and 5-HT(3) receptors. Compounds 1-11 were synthesized and evaluated for binding affinity at both serotoninergic receptors, all of them exhibiting high 5-HT(3)R affinity (K(i)=10-62nM), and derivatives with an o-alkoxy group in the arylpiperazine

  通过在一般结构III中结合5-HT（1A）和5-HT（3）受体的药效学元素，设计了一系列新的混合苯并咪唑-芳基哌嗪衍生物。合成了化合物1-11，并评估了它们在两个5-羟色胺能受体上的结合亲和力，它们均显示出较高的5-HT（3）R亲和力（K（i）= 10-62nM），以及在化合物中具有邻烷氧基的衍生物芳基哌嗪环显示对5-HT（1A）R的纳摩尔亲和力（K（i）= 18-150nM）。此外，所有合成的化合物对α（1）-肾上腺素和多巴胺D（2）受体具有选择性（K（i）> 1000-10,000nM）。由于化合物3作为混合的5-HT（1A）/ 5-HT（3）配体对两个受体都具有高亲和力（5-HT（1A）：K（i）= 18.0 nM，5-HT（3）：K（i）＝ 27.2nM）。体外和体内发现表明，该化合物在5-HT（1A）Rs和5-HT（3）R拮抗剂中起部分激动剂的作用。这种新颖的混合5-HT（1A）/
• [EN] COMPOUNDS FOR BINDING PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9)<br/>[FR] COMPOSÉS SE LIANT À LA PROPROTÉINE CONVERTASE SUBTILISINE/KEXINE DE TYPE 9 (PCSK9)
  申请人：PORTOLA PHARM INC

  公开号：WO2017147328A1

  公开（公告）日：2017-08-31

  The present disclosure relates to novel compounds, methods, and compositions capable of binding to PCSK9, thereby modulating PCSK9 proprotein convertase enzyme activity. The compounds of the disclosure include compounds Formula (I).

  本公开涉及与PCSK9结合的新化合物、方法和组合物，从而调节PCSK9前蛋白酶酶活性。本公开的化合物包括化合物式（I）。
• Synthesis of New Serotonin 5-HT₇ Receptor Ligands. Determinants of 5-HT₇/5-HT_1A Receptor Selectivity
  作者：Rocío A. Medina、Jessica Sallander、Bellinda Benhamú、Esther Porras、Mercedes Campillo、Leonardo Pardo、María L. López-Rodríguez

  DOI：10.1021/jm8014553

  日期：2009.4.23

  We report the synthesis of a new set of compounds of general structure I (1-20) with structural modifications in the pharmacophoric elements of the previously reported lead UCM-5600. The new derivatives have been evaluated for binding affinity at 5-HT7 and 5-HT1A receptors. The influence of the different structural features in terms of 5-HT7/5-HT1A receptor affinity and selectivity was analyzed by computational simulations of the complexes between compounds I and beta(2)-based 3-D models of these receptors. Compound 18 (HYD1 = 1,3-dihydro-2H-indol-2-one; spacer = -(CH2)(4)-; HYD2 + HYD3 = 3,4-dihydroisoquinolin-2(1H)-yl) exhibits high 5-HT7R affinity (K-i = 7 nM) and selectivity over the 5-HT1AR (31-fold), and has been characterized as a partial agonist of the human 5-HT7R.
• Synthesis of new (benzimidazolyl)piperazines with affinity for the 5-HT1A receptor via Pd(0) amination of bromobenzimidazoles
  作者：María L López-Rodríguez、Alma Viso、Bellinda Benhamú、J.Luis Rominguera、Marta Murcia

  DOI：10.1016/s0960-894x(99)00384-4

  日期：1999.8

  The synthesis of a new family of (benzimidazolyl)piperazines has been developed through Pd(0) mediated amination of 4- and 6-bromobenzimidazole derivatives. Preliminary studies showed that some of these compounds are potent 5-HT1A receptor ligands. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 8. Computational Simulation of Ligand−Receptor Interaction of 5-HT_1AR Agonists with Selectivity over α₁-Adrenoceptors
  作者：María L. López-Rodríguez、Maria José Morcillo、Esther Fernández、Bellinda Benhamú、Ignacio Tejada、David Ayala、Alma Viso、Mercedes Campillo、Leonardo Pardo、Mercedes Delgado、Jorge Manzanares、José A. Fuentes

  DOI：10.1021/jm048999e

  日期：2005.4.1

  We have designed and synthesized a new series of arylpiperazines V exhibiting high 5-HT1AR affinity and selectivity over alpha(1)-adrenoceptors. The new selective 5-HT1AR ligands contain a hydantoin (m = 0) or diketopiperazine (m = 1) moiety and an arylpiperazine moiety separated by one methylene unit (n = 1). The aryl substituent of the piperazine moiety (Ar) consists of different benzofused rings mimicking the favorable voluminous substituents at ortho and meta positions predicted by 3D-QSAR analysis in the previously reported series I. In particular, (S)-2-[[4-(naphth-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-a]pyrazine [(S)-9, CSP-2503] (5-HT1A, K-i = 4.1 nM; alpha(1), Ki > 1000 nM) has been pharmacologically characterized as a 5-HT1AR agonist at somatodendritic and postsynaptic sites, endowed with anxiolytic properties. Ligand (S)-9 is predicted, in computer simulations, to bind Asp(3.32) in TMH 3, Thr(5.39) and Ser(5.42) in TMH 5, and Trp(6.48) in TMH 6. We propose that agonists modify, by means of an explicit hydrogen bond, the conformation of Trp(6.48) from pointing toward TMH 7, in the inactive gauche+ conformation, to pointing toward the ligand binding site, in the active trans conformation.