1-(4,4'-dicyanodiphenylmethyl)-1H-imidazole

• 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: 1-(4,4'-dicyanodiphenylmethyl)-1H-imidazole
• 英文别名: 4-[α-(4-cyanophenyl)-(1-imidazolyl)methyl]-benzonitrile；4-[α-(4-cyanophenyl)-(1-imidazolyl)methyl]benzonitrile；4-[α-(4-cyanophenyl)-1-imidazolylmethyl]-benzonitrile；4-[alpha-(4-cyanophenyl)-1-imidazolylmethyl]-benzonitrile；4-[(4-Cyanophenyl)-imidazol-1-ylmethyl]benzonitrile
• 化学式: C₁₈H₁₂N₄
• 分子量: 284.32
• InChiKey: NRXVWQIGPASRKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  65.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4,4'-dicyanodiphenylmethyl)-1H-imidazole 生成 butanedioic acid;4-[(4-cyanophenyl)-imidazol-1-ylmethyl]benzonitrile
  参考文献：
  名称：

  BOWMAN, ROBERT M.;STEELE, RONALD E.;BROWNE, LESLIE J.

  摘要：

  DOI：
• 作为产物：
  描述：

  对氰基溴化苄 在 potassium tert-butylate 、 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 2.5h， 生成 1-(4,4'-dicyanodiphenylmethyl)-1H-imidazole
  参考文献：
  名称：

  Synthesis and structure–activity relationship of 1- and 2-substituted-1,2,3-triazole letrozole-based analogues as aromatase inhibitors

  摘要：

  A series of bis- and mono-benzonitrile or phenyl analogues of letrozole 1, bearing (1,2,3 and 1,2,5)-triazole or imidazole, were synthesized and screened for their anti-aromatase activities. The unsubstituted 1,2,3-triazole 10a derivative displayed inhibitory activity comparable with that of the aromatase inhibitor, letrozole I. Compound 10a, bearing a 1,2,3-triazole, is also 10000-times more tightly binding than the corresponding analogue 25 bearing a 1,2,5-triazole, which confirms the importance of a nitrogen atom at position 3 or 4 of the 5-membered ring needed for high activity. The effect on human epithelial adrenocortical carcinoma cell line (H295R) proliferation was also evaluated. The compound 10j (IC50 = 4.64 mu M), a letrozole 1 analogue bearing para-cyanophenoxymethylene-1,2,3-triazole decreased proliferation rates of H295R cells by 76 and 99% in 24 and 72 h respectively. Computer calculations, using quantum ab initio structures, suggest a possible correlation between anti-aromatase activity and the distance between the nitrogen in position 3 or 4 of triazole nitrogen and the cyano group nitrogen. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.074

文献信息

• [EN] USE OF AN AROMATASE INHIBITOR FOR THE TREATMENT OF HYPOGONADISM AND RELATED DISEASES<br/>[FR] UTILISATION D'UN INHIBITEUR D'AROMATASE POUR LE TRAITEMENT DE L'HYPOGONADISME ET DE MALADIES APPARENTÉES
  申请人：NOVARTIS AG

  公开号：WO2013036562A1

  公开（公告）日：2013-03-14

  This invention relates to a method of increasing testosterone levels and treating hypogonadism and related diseases with the aromatase inhibitor 4,4'-[fluoro-(1-H-1,2,4-triazol-1-yl)methylene]bisbenzonitrile. The present invention further relates to a method of increasing testosterone levels and treating hypogonadism and related diseases with the aromatase inhibitor 4,4'-[fluoro-(1-H-1,2,4-triazol-1-yl)methylene]bisbenzonitrile in a particular dosing regimen. The invention also relates to pharmaceutical compositions comprising said aromatase inhibitor 4,4'-[fluoro-(1-H-1,2,4-triazol-1-yl)methylene]bisbenzonitrile, optionally in combination with other active ingredients. Furthermore, the present invention relates to kits comprising said pharmaceutical compositions together with instructions how to administer them.

  本发明涉及一种使用芳香酶抑制剂4,4'-[氟-(1-H-1,2,4-三唑-1-基)亚甲基]双苯腈来提高睾酮水平并治疗低睾酮血症及相关疾病的方法。本发明进一步涉及在特定的剂量方案下，使用芳香酶抑制剂4,4'-[氟-(1-H-1,2,4-三唑-1-基)亚甲基]双苯腈来提高睾酮水平并治疗低睾酮血症及相关疾病的方法。本发明还涉及包含所述芳香酶抑制剂4,4'-[氟-(1-H-1,2,4-三唑-1-基)亚甲基]双苯腈的药物组合物，可选地与其他活性成分结合使用。此外，本发明还涉及包含所述药物组合物以及使用说明的试剂盒。
• Contraception in female primates without affecting the menstrual cycle
  申请人：Ciba-Geigy Corporation

  公开号：US05583128A1

  公开（公告）日：1996-12-10

  The invention relates to the use of aromatase inhibitors for contraception in female primates and to a method for contraception in female primates using such substances and to the use of those substances for the preparation of pharmaceutical compositions for contraception in female primates.

  该发明涉及在雌性灵长类动物中使用芳香化酶抑制剂进行避孕，以及使用这些物质进行雌性灵长类动物避孕的方法，以及利用这些物质制备用于雌性灵长类动物避孕的药物组合物。
• .alpha.-fluoro-.alpha.-tetrazolyl-phenylmethyl derivatives useful as
  申请人：Ciba-Geigy Corporation

  公开号：US05227393A1

  公开（公告）日：1993-07-13

  Compounds of formula I ##STR1## wherein Z, R, R.sub.1, R.sub.2 and X are as defined in the description, have valuable pharmaceutical properties and are effective especially against tumours. They are prepared in a manner known per se.

  式I的化合物，其中Z、R、R₁、R₂和X如描述中定义，具有宝贵的药理特性，特别对抗肿瘤有效。它们以已知的方式制备。
• Methods and compositions for the treatment of estrogen-dependent hyperproliferative uterine disorders
  申请人：Wang Changjin

  公开号：US20100087402A1

  公开（公告）日：2010-04-08

  The present invention relates to the treatment of estrogen-dependent hyperproliferative uterine disorders including endometriosis, uterine fibroids, endometrial hyperplasia, uterine cancer, and their related symptoms by intravaginally administering at least two active agents selected from an aromatase inhibitor, an antiinflammatory agent, and a uterine-selective estrogen receptor antagonist. This combination therapy reduces local estrogen production, blocks local estrogen action, and suppresses inflammation locally, resulting in starvation of the estrogen-dependent diseased tissues, relief of related symptoms, and retardation of disease progression. Intravaginal delivery maximizes local inhibition of estrogen production without significantly affecting systemic circulating estrogen levels. This results in enhanced clinical efficacy and reduced side effects.

  本发明涉及治疗依赖雌激素的子宫过度增生性疾病，包括子宫内膜异位症、子宫肌瘤、子宫内膜增生、子宫癌及其相关症状，通过阴道给药至少两种活性药物，所选药物包括芳香化酶抑制剂、抗炎药和子宫选择性雌激素受体拮抗剂。这种联合疗法降低了局部雌激素产生，阻断了局部雌激素作用，并在局部抑制了炎症，导致对依赖雌激素的疾病组织的饥饿，缓解相关症状，延缓疾病进展。阴道给药最大限度地抑制了局部雌激素产生，而不显著影响全身循环雌激素水平。这导致增强的临床疗效和减少的副作用。
• [EN] PHARMACEUTICAL COMBINATION FOR THE TREATMENT OF BENIGN PROSTATIC HYPERPLASIA COMTAINING A 5 ALPHA-REDUCTASE INHIBITOR
  申请人：MERCK & CO., INC.

  公开号：WO1992018132A1

  公开（公告）日：1992-10-29

  (EN) Disclosed is a new treatment for men with benign prostatic hyperplasia (BPH), involving combination therapy of a 5$g(a)-reductase inhibitor, e.g. a 17$g(b)-substituted non-azasteroid, 17$g(b)-acyl-3-carboxy-androst-3,5-diene, benzoylaminophenoxybutanoic acid derivative, fused benz(thio)amide or cinnamoylamide derivative, aromatic 1,2-diethers or thioethers, aromatic ortho acylaminophenoxy alkanoic acids, ortho thioalkylacylamino-phenoxy alkanoic acids, pharmaceutically acceptable salts and esters thereof, e.g. finsteride, in combination with an aromatase inhibitor, i.e., fadrazole, being 4-(5,6,7,8-tetra-hydroimidazo-[1,5-$g(a)]pyridin-5-yl)benzonitrile. The combination provides therapy at the molecular level for the underlying cause of the disease as well as providing symptomatic relief. Pharmaceutical compositions useful for treatment are also disclosed.(FR) On décrit un nouveau traitement destiné aux hommes souffrant d'hyperplasie prostatique bénigne (HPB), et qui comprend une thérapie d'association composée d'un inhibiteur de 5$g(a)-réductase, par exemple un dérivé d'acide benzoylaminophénoxybutanoïque, 17$g(b)-substitué non azastéroïde, 17$g(b)-acyl-3-carboxy-androst-3,5-diène, un dérivé de cinnamoylamide ou de benz(thio)amide fusionné, des thioéthers ou 1,2-diéthers aromatiques, des acides alcanoïques aromatiques d'ortho acylaminophénoxy, des acides alcanoïques d'ortho thioalkylacylamino-phénoxy, des sels et des esters pharmaceutiquement acceptables de ces éléments, par exemple de la finastéride, en association avec un inhibiteur d'aromatase, c'est-à-dire du fadrazole, étant composé de 4-(5,6,7,8-tétrahydro-imidazo-[1,5-$g(a)]pyridin-5-yle) benzonitrile. L'association constitue une thérapie au niveau moléculaire dirigée contre la cause sous-jacente de la maladie tout en produisant un soulagement symptomatique. Des compositions pharmaceutiques utilisées pour ce traitement sont aussi décrites.

  该专利公开了一种新的治疗良性前列腺增生（BPH）的方法，涉及使用5α-还原酶抑制剂的联合治疗，例如17β-取代的非阿扎斯特罗伊德类、17β-酰基-3-羧基-雄烯-3,5-二烯、苯甲酰氨基苯氧丁酸衍生物、融合苯（硫）酰胺或肉桂酰胺衍生物、芳香族1,2-二醚或硫醚、芳香族正交酰胺基苯氧基烷酸、正交硫烷基酰胺基苯氧基烷酸，以及其药学上可接受的盐和酯，例如非那雄胺，与芳香化酶抑制剂，即4-（5,6,7,8-四氢咪唑[1,5-a]吡啶-5-基）苯甲腈的联合使用。该联合疗法在分子水平上治疗疾病的根本原因，并提供症状缓解。还公开了用于治疗的药物组合。