Histaprodifen | 222545-59-7

• 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: Histaprodifen
• 英文别名: 2-[2-(3,3-diphenylpropyl)-1H-imidazol-5-yl]ethanamine
• CAS: 222545-59-7
• 化学式: C₂₀H₂₃N₃
• 分子量: 305.423
• InChiKey: BPZGZNLONLANFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Histaprodifen 在 吡啶 、 N,N'-羰基二咪唑 、 diborane(6) 作用下， 以 四氢呋喃 为溶剂， 反应 21.0h， 生成 {2-[2-(3,3-Diphenyl-propyl)-1H-imidazol-4-yl]-ethyl}-(4-pyridin-2-yl-butyl)-amine
  参考文献：
  名称：

  组胺的Nα-咪唑基烷基和吡啶烷基烷基衍生物：高效组胺H（1）-受体激动剂的合成和体外评估。

  摘要：

  合成了一系列新的组胺苯丙胺的N（α）（）-咪唑基烷基和吡啶基烷基衍生物（6，2- [2-（3,3-二苯丙基）咪唑--4-基]乙胺）并评估为组胺H（1） -受体激动剂。标题化合物在豚鼠回肠的收缩性H（1）受体上表现出部分激动作用，并且至少与组胺等价。新衍生物的激动剂作用易于受到H（1）-受体拮抗剂美吡拉敏（2-100 nM）的阻滞。在咪唑系列中，suprahistaprodifen（51，[2- [2-（3,3-二苯丙基）-1H-咪唑-4-基]乙基]-[2-（1H-咪唑-4-基）乙基]酰胺，N（α）-2-[（（1H-咪唑-4-基）乙基]组己二酚）显示出有史以来最高的H（1）-受体激动剂效能（pEC（50）8.26，功效E（max） 96％）。烷基间隔物从乙基到丁基的延伸将活性从3630％（乙基，51）降低到163％（丁基，53）组胺效力。末端咪唑核交换成吡啶环产生具有相当高效力的化合物。当烷

  DOI：

  10.1021/jm0309147
• 作为产物：
  描述：

  4,4-二苯基丁腈 在 氯化亚砜 、 氨 、 一水合肼 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 Histaprodifen
  参考文献：
  名称：

  Histaprodifens：合成，药理学体外评价和新型的高活性和选择性组胺H（1）-受体激动剂的新型分子模型。

  摘要：

  通过将相应的亚氨酸甲酯5b与2-氧代-环戊基环合，从4,4-二苯基丁腈（4b）制备了一类新的组胺类似物，其特征是在咪唑核的2位上有一个3，3-二苯丙基取代基。在液氨中的4-邻苯二甲酰亚胺基-1-乙酸丁酯或2-氧代-1,4-丁二醇，然后进行标准反应。标题化合物分别对豚鼠回肠和内皮剥脱的主动脉的收缩性H（1）受体表现出部分激动作用，但10（组胺布洛芬; 2- [2-（3，3-二苯丙基）-1H-咪达唑-4）除外-基]乙胺），在回肠测定中是完全激动剂。虽然10与组胺（1）等价，但是甲基组蛋白（13）和二甲基组蛋白（14）的功能效价比1高出3-5（13）和2-3（14）。化合物10和13-17放松了预收缩的大鼠主动脉环（完整内皮），相对效力为3.3至28倍（与1相比），也表现出部分激动作用。激动剂的作用对选择性H（1）-受体拮抗剂美吡拉敏（pA（2）约9（几内亚猪）和pA（2）约8（大鼠主动脉）的封

  DOI：

  10.1021/jm991056a

文献信息

• Ring-substituted histaprodifen analogues as partial agonists for histamine H1 receptors: synthesis and structure–activity relationships
  作者：S Elz

  DOI：10.1016/s0223-5234(00)00105-7

  日期：2000.1

  Thirteen racemic benzene ring-substituted analogues of histaprodifen (8a; 2-[2-(3,3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine), a novel lead for potent and selective histamine H-1-receptor agonists, have been prepared from substituted 4,4-diphenylbutyronitriles 5 via cyclization of the corresponding methyl butyrimidates 6 with 2-oxo-4-phthalimido-1-butyl acetate in liquid ammonia, followed by deprotection. Nitriles 5 were accessible by alkylation of either substituted diphenylmethanes with 3-bromopropionitrile or diethyl malonate with substituted 1-chloro-diphenylmethanes and subsequent standard reactions. The title compounds 8 displayed partial agonism on contractile H-1 receptors of the guinea-pig ileum (E-max = 2-98% relative to histamine) and, compared with the endogenous agonist, were endowed with agonist potencies of 4-92%. The meta fluorinated (gc) and meta chlorinated (8f) analogues showed the highest relative potency in this series (95% confidence Limits 85-99% and 78-102%), but did not exceed the value of the lead 8a (99-124%). Compound 8c (2-[2-[3-(3-fluorophenyl)-3-phenylpropyl]-1H-imidazol-4-yl]ethanamine) was a partial agonist at contractile H-1 receptors of the guinea-pig aorta (relative potency 154% vs. 100% for histamine) and at relaxation-mediating endothelial H-1 receptors of the rat aorta (relative potency 556% vs. 100% for histamine) and matched with the functional behaviour of 8a. Agonism observed for each compound was sensitive to blockade by the selective H-1-receptor antagonist mepyramine (pA(2) approximate to 9 (guinea-pig) and pA(2) approximate to 8 (rat aorta)). All histaprodifen analogues 8 stimulated neither histaminergic H-2/H-3, nor cholinergic M-3 receptors. They displayed only low to moderate affinity for these sites (H-2: pD'(2), < 5; H-3/M-3: pA(2) < 6). With regard to the substitution pattern on the benzene ring, there was no correlation between the histaprodifen series and the corresponding derivatives of another selective H-1-receptor agonist, viz. 2-phenylhistamine. (C) 2000 Editions scientifiques et medicales Elsevier SAS.
• GPCR MODULATORS
  申请人：Board of Trustees of Michigan State University

  公开号：EP1885708A2

  公开（公告）日：2008-02-13
• IMPROVING THE TOLERABILITY OF MIRTAZAPINE AND A SECOND ACTIVE BY USING THEM IN COMBINATION
  申请人：Cypress Bioscience, Inc.

  公开号：EP2167096A1

  公开（公告）日：2010-03-31
• Aminergic pharmaceutical compositions and methods
  申请人：Dillon Patrick F.

  公开号：US20090156581A1

  公开（公告）日：2009-06-18

  Pharmaceutical compositions and method using aminergic compounds and complement compounds. Compositions are provided comprising: (a) a subefficacious amount of a non-adrenergic aminergic compound or of an adrenergic antagonist; and (b) a safe and effective amount of a complement compound. Methods are also provided comprising the administration of: (a) a low dose of a non-adrenergic aminergic compound or of any adrenergic antagonist; and (b) a safe and effective amount of a complement compound. Non-adrenergic aminergic compounds can comprise a histaminergic, dopaminergic, muscarinergic, serotoninergic, octopaminergic, or trace aminergic compound. Complement compounds include ascorbates, opioids, polycarboxylic acid chelators, resveratrols, cysteines, substituted derivatives and analogs thereof, and mixtures thereof. Preferred complements include ascorbates, particularly ascorbic acid. Methods include the treatment of: neurological and neural disorders; mood and behavior disorders; cardiac, vascular, and cardiovascular disorders; hypertension, headache; respiratory disorders; gastrointestinal disorders; obesity; asthma, allergy; smooth muscle contraction disorders; nasal or nasopharyngeal conditions; genitourinary disorders; ocular disorders, glaucoma; hormone- or neurotransmitter-release or -secretion disorders.
• TOLERABILITY OF MIRTAZAPINE AND A SECOND ACTIVE BY USING THEM IN COMBINATION
  申请人：Rao Srinivas

  公开号：US20090275562A1

  公开（公告）日：2009-11-05

  A reduction in the side effects of treating with an agent having combined 5HT 2 /5HT 3 and alpha-2 antagonistic activity is obtained by administering an agent having selective norepinephrine reuptake inhibitory or histamine H1 agonist activity. In some embodiments, the invention provides synergistic combinations of 5HT 2 /5HT 3 antagonist/alpha-2 antagonist and selective norepinephrine reuptake inhibitor or histamine H1 agonist.