1-benzyl-5-[4-(4-fluorophenyl)-1-hydroxy-1-(4-tert-butylaminocarbonylphenyl)butyl]-1H-imidazole | 147223-89-0

• 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-benzyl-5-[4-(4-fluorophenyl)-1-hydroxy-1-(4-tert-butylaminocarbonylphenyl)butyl]-1H-imidazole
• 英文别名: 1-benzyl-5-[4-(4-fluorophenyl)-1-hydroxy-1-(4-tert-butylaminocarbonylphenyl)butyl]-1-H-imidazole；4-[1-(3-benzylimidazol-4-yl)-4-(4-fluorophenyl)-1-hydroxybutyl]-N-tert-butylbenzamide
• CAS: 147223-89-0
• 化学式: C₃₁H₃₄FN₃O₂
• 分子量: 499.628
• InChiKey: YNROJSQZXHMZHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-benzyl-5-[4-(4-fluorophenyl)-1-hydroxy-1-(4-tert-butylaminocarbonylphenyl)butyl]-1H-imidazole 在 palladium-carbon ammonium formate 作用下， 以 乙醇 、 水 为溶剂， 生成 4-[4-(4-fluorophenyl)-1-hydroxy-1-(4-tert-butylaminocarbonylphenyl)butyl]-1H-imidazole
  参考文献：
  名称：

  Selective aromatase inhibiting 4(5)-imidazoles

  摘要：

  公式（Ia）和（Ib）的新4（5）-咪唑衍生物，其中R.sub.1和R.sub.2中的一个为CN，另一个为H，CH.sub.3，OCH.sub.3，NO.sub.2，NH.sub.2，CN，CF.sub.3，CHF.sub.2，CH.sub.2 F或卤素; R'为H或（II），其中R.sub.3为H，CH.sub.3或卤素; R.sub.4为H，R.sub.5为H或R.sub.4和R.sub.5共同形成键，n为1或2，y为0到2，它们的立体异构体及其无毒药物可接受的酸盐具有比它们的去甲肾上腺素酶抑制作用更具有选择性的芳香化酶抑制作用。本发明的化合物在治疗雌激素依赖性疾病，例如乳腺癌或良性前列腺增生症（BPH）方面具有价值。

  公开号：

  US05559141A1
• 作为产物：
  描述：

  1-(3-溴丙基)-4-氟苯 在 manganese(IV) oxide 、 正丁基锂 、 magnesium 作用下， 以 四氢呋喃 、 四氯乙烯 为溶剂， 反应 8.0h， 生成 1-benzyl-5-[4-(4-fluorophenyl)-1-hydroxy-1-(4-tert-butylaminocarbonylphenyl)butyl]-1H-imidazole
  参考文献：
  名称：

  Synthesis of new potent and selective aromatase inhibitors based on long-chained diarylalkylimidazole and diarylalkyltriazole molecule skeletons

  摘要：

  A series of long-chained diarylalkylimidazoles and diarylalkyltriazoles were synthesized and evaluated for the inhibitory potency for aromatase (estrogen synthetase) activity in human placental microsomes. The relative specificity of inhibition was evaluated by measuring the inhibition of cholesterol side-chain cleavage enzyme (desmolase) in human placental mitochondria and the inhibition of 7-ethoxycoumarin O-deethylase (a typical drug-metabolizing enzyme activity) in rat liver microsomes. The structural requirements including substituent effects for the strongest potency and for the highest specificity were delineated. alpha,omega-Diarylalkyltriazoles and imidazoles were the most interesting molecules, in which the geometric and optical isomerism displayed remarkable selectivity for aromatase inhibition. (C) 2000 Elsevier Science B.V. All rights reserved.

  DOI：

  10.1016/s0928-0987(00)00074-9

文献信息

• NEW SELECTIVE AROMATASE INHIBITING 4(5)-IMIDAZOLES
  申请人：ORION-YHTYMÄ OY

  公开号：EP0589975A1

  公开（公告）日：1994-04-06
• US5559141A
  申请人：——

  公开号：US5559141A

  公开（公告）日：1996-09-24
• [EN] NEW SELECTIVE AROMATASE INHIBITING 4(5)-IMIDAZOLES
  申请人：ORION-YHTYMÄ OY

  公开号：WO1992022537A1

  公开（公告）日：1992-12-23

  (EN) New 4(5)-imidazole derivatives of formula (Ia) and (Ib) wherein one of R1 and R2 is CN and the other one is H, CH3, OCH3, NO2, NH2, CN, CF3, CHF2, CH2F or halogen; R' is H or (II) where R3 is H, CH3 or halogen; R4 is H and R5 is H or R4 and R5 together form a bond, n is 1 or 2 and y is 0 to 2, their stereoisomers and their non-toxic pharmaceutically acceptable acid addition salts exhibit selective aromatase inhibiting properties, compared with their desmolase inhibiting properties. The compounds of the invention are valuable in the treatment of estrogen dependent diseases, e.g. breast cancer or benign prostatic hyperplasia (BPH).(FR) Nouveaux dérivés de 4(5)-imidazole répondant à la formule (Ia) et (Ib), dans laquelle R1 ou R2 représente CN alors que l'autre représente H, CH3, OCH3, NO2, NH2, CN, CF3, CHF2, CH2F ou halogène; R' représente H ou (II), où R3 représente H, CH3 ou halogène; R4 représente H et R5 représente H, ou R4 et R5, pris ensemble, forment une liaison; n est 1 ou 2 et y est compris entre 0 et 2; leurs stéréoisomères et leurs sels d'addition d'acide pharmaceutiquement acceptables et non toxiques, présentent des caractéristiques d'inhibition sélective d'aromatase, comparées à leurs caractéristiques d'inhibition de desmolase. Ces composés sont utilisés pour le traitement des maladies dépendant de l'oestrogène telles que le cancer du sein ou l'adénome prostatique.
• Synthesis of new potent and selective aromatase inhibitors based on long-chained diarylalkylimidazole and diarylalkyltriazole molecule skeletons
  作者：Arto Karjalainen、Arja Kalapudas、Marja Södervall、Olavi Pelkonen、Risto Lammintausta

  DOI：10.1016/s0928-0987(00)00074-9

  日期：2000.8

  A series of long-chained diarylalkylimidazoles and diarylalkyltriazoles were synthesized and evaluated for the inhibitory potency for aromatase (estrogen synthetase) activity in human placental microsomes. The relative specificity of inhibition was evaluated by measuring the inhibition of cholesterol side-chain cleavage enzyme (desmolase) in human placental mitochondria and the inhibition of 7-ethoxycoumarin O-deethylase (a typical drug-metabolizing enzyme activity) in rat liver microsomes. The structural requirements including substituent effects for the strongest potency and for the highest specificity were delineated. alpha,omega-Diarylalkyltriazoles and imidazoles were the most interesting molecules, in which the geometric and optical isomerism displayed remarkable selectivity for aromatase inhibition. (C) 2000 Elsevier Science B.V. All rights reserved.
• Selective aromatase inhibiting 4(5)-imidazoles
  申请人：Orion-yhtyma Oy

  公开号：US05559141A1

  公开（公告）日：1996-09-24

  New 4(5)-imidazole derivatives of formula (Ia) and (Ib) wherein one of R.sub.1 and R.sub.2 is CN and the other one is H, CH.sub.3, OCH.sub.3, NO.sub.2, NH.sub.2, CN, CF.sub.3, CHF.sub.2, CH.sub.2 F or halogen; R' is H or (II) where R.sub.3 is H, CH.sub.3 or halogen; R.sub.4 is H and R.sub.5 is H or R.sub.4 and R.sub.5 together form a bond, n is 1 or 2 and y is 0 to 2, their stereoisomers and their non-toxic pharmaceutically acceptable acid addition salts exhibit selective aromatase inhibiting properties, compared with their desmolase inhibiting properties. The compounds of the invention are valuable in the treatment of estrogen dependent diseases, e.g. breast cancer or benign prostatic hyperplasia (BPH).

  公式（Ia）和（Ib）的新4（5）-咪唑衍生物，其中R.sub.1和R.sub.2中的一个为CN，另一个为H，CH.sub.3，OCH.sub.3，NO.sub.2，NH.sub.2，CN，CF.sub.3，CHF.sub.2，CH.sub.2 F或卤素; R'为H或（II），其中R.sub.3为H，CH.sub.3或卤素; R.sub.4为H，R.sub.5为H或R.sub.4和R.sub.5共同形成键，n为1或2，y为0到2，它们的立体异构体及其无毒药物可接受的酸盐具有比它们的去甲肾上腺素酶抑制作用更具有选择性的芳香化酶抑制作用。本发明的化合物在治疗雌激素依赖性疾病，例如乳腺癌或良性前列腺增生症（BPH）方面具有价值。