5-(4-cyanophenyl)-6,7,8,9-tetrahydro-5H-imidazo<1,5-a>azepine | 102676-74-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 5-(4-cyanophenyl)-6,7,8,9-tetrahydro-5H-imidazo<1,5-a>azepine
• 英文别名: 5H-5-(4-cyanophenyl)-6,7,8,9-tetrahydroimidazo[1,5-a]azepine；4-(6,7,8,9-Tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)-benzonitrile；4-(6,7,8,9-tetrahydro-5H-imidazo[1,5-a]azepin-5-yl)benzonitrile
• CAS: 102676-74-4
• 化学式: C₁₅H₁₅N₃
• 分子量: 237.304
• InChiKey: IVAZIKNYMMXRJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-<5-<4-<(tert-butylamino)carbonyl>phenyl>-5-chloropent-1-yl>-1-(triphenylmethyl)-1H-imidazole 在 氯化亚砜 作用下， 反应 31.0h， 生成 5-(4-cyanophenyl)-6,7,8,9-tetrahydro-5H-imidazo<1,5-a>azepine
  参考文献：
  名称：

  Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease

  摘要：

  A new class of potent, selective, nonsteroidal inhibitors of aromatase have been discovered. The most potent member of this series is fadrozole hydrochloride, CGS 16949 A, 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile monohydrochloride, 26a. In addition, the 6,7-dihydropyrrolo[1,2-c]imidazole (21a) and the 6,7,8,9-tetrahydroimidazo[1,5-a]azepine (21b) analogues were synthesized and evaluated. CGS 16949 A's ability to selectively inhibit aromatase (IC50 = 4.5nM) over other cytochrome P-450 enzymes and suppress estrogen production when administered orally make it a suitable candidate to test the potential of an aromatase inhibitor in estrogen-dependent diseases including breast cancer.

  DOI：

  10.1021/jm00106a038

文献信息

• [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。
• Verwendung von bicyclischen Imidazol-Verbindungen zur Behandlung von Hyperaldosteronismus
  申请人：CIBA-GEIGY AG

  公开号：EP0366609A2

  公开（公告）日：1990-05-02

  Die Erfindung betrifft die Verwendung von gewissen bicyclischen Imidazol-­Verbindungen, wie 5-(p-Cyanphenyl)-5,6,7,8-tetrahydroimidazo[1,5-a]-­pyridin, oder pharmazeutisch verwendbaren, nicht-toxischen Salzen davon zur Behandlung von Hyperaldosteronismus, bzw. ein Verfahren zur Behand­lung von Hyperaldosteronismus unter Verwendung von solchen Verbindungen, bzw. die Verwendung dieser Verbindungen zur Herstellung von pharmazeu­tischen Präparaten für die Behandlung von Hyperaldosteronismus.

  本发明涉及某些双环咪唑化合物，如5-(对氰基苯基)-5,6,7,8-四氢咪唑并[1,5-a]-吡啶，或其药学上可接受的无毒盐用于治疗高醛固酮症，或使用此类化合物治疗高醛固酮症的方法，或使用这些化合物制造治疗高醛固酮症的药物组合物。
• Use of aromatese inhibitors for the reversal of female sexual phenotype in poultry
  申请人：MERCK & CO. INC.

  公开号：EP0433084A2

  公开（公告）日：1991-06-19

  Fertilized poultry embryos are treated with steroid biosynthesis inhibitors or antagonists which prevents the conversion of androgens to estrogens. By blocking the production of estrogens the genotypic female is converted into a phenotypic male. The phenotypic conversion of females to males gives the treated birds the advantage of male growth characteristics. A single administration of a steroid biosynthesis inhibitor or antagonist prior to about day 9 of embryonic incubation results in an irreversible change the sexual phenotype.

  用类固醇生物合成抑制剂或拮抗剂处理受精的家禽胚胎，可防止雄激素转化为雌激素。通过阻止雌激素的产生，基因型雌性就会转化为表型雄性。雌性向雄性的表型转换使接受治疗的鸟类具有雄性生长特征的优势。在胚胎孵化的第 9 天之前，只需注射一次类固醇生物合成抑制剂或拮抗剂，就会导致性表型发生不可逆的改变。
• Animal growth promotion with aromatase inhibitors
  申请人：MERCK & CO. INC.

  公开号：EP0479570A2

  公开（公告）日：1992-04-08

  Female prenatal, neonatal and postnatal animals are treated with compositions containing steroid biosynthesis inhibitors or antagonists which prevents the conversion of androgens to estrogens. The compositions are useful for improving growth and feed efficiency.

  雌性产前、新生和产后动物可使用含有类固醇生物合成抑制剂或拮抗剂的组合物进行治疗，以防止雄激素转化为雌激素。这些复合物可用于改善生长和提高饲料效率。
• Control of sex differentiation in fish
  申请人：MERCK & CO. INC.

  公开号：EP0514015A1

  公开（公告）日：1992-11-19

  Fish or shellfish eggs, fertilized embryos or hatched fry or shellfish are treated with steroid biosynthesis inhibitors or antagonists which prevents the conversion of androgens to estrogens. By blocking the production of estrogens the genotypic female is converted into a phenotypic male. The phenotypic conversion of females to males gives the treated fish the advantage of male growth characteristics. Such treatment will also allow the production of monosex populations of fish which can be used to limit reproduction and control overpopulation of specific aquatic environments. Steroid biosynthesis inhibitors and/or antagonists will also induce smoltification in salmon species.

  用类固醇生物合成抑制剂或拮抗剂处理鱼类或贝类的卵、受精胚胎或孵化的鱼苗或贝类，可防止雄激素转化为雌激素。通过阻止雌激素的产生，基因型雌性就会转化为表型雄性。雌性向雄性的表型转化使接受治疗的鱼类具有雄性生长特征的优势。这种处理方法还能产生单性鱼群，用于限制繁殖和控制特定水生环境中的过度繁殖。类固醇生物合成抑制剂和/或拮抗剂还能诱导鲑鱼物种的蜕皮。