(4-Chloro-phenyl)-[5-(3-chloro-phenyl)-1,2,3,9b-tetraaza-cyclopenta[a]naphthalen-7-yl]-(3-methyl-3H-imidazol-4-yl)-methanol | 280143-53-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (4-Chloro-phenyl)-[5-(3-chloro-phenyl)-1,2,3,9b-tetraaza-cyclopenta[a]naphthalen-7-yl]-(3-methyl-3H-imidazol-4-yl)-methanol
• 英文别名: (4-Chlorophenyl)-[5-(3-chlorophenyl)tetrazolo[1,5-a]quinolin-7-yl]-(3-methylimidazol-4-yl)methanol
• CAS: 280143-53-5
• 化学式: C₂₆H₁₈Cl₂N₆O
• 分子量: 501.375
• InChiKey: HTKBESMXWXJVMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-Chloro-phenyl)-[5-(3-chloro-phenyl)-1,2,3,9b-tetraaza-cyclopenta[a]naphthalen-7-yl]-(3-methyl-3H-imidazol-4-yl)-methanol 在 氯化亚砜 作用下， 生成 7-[Chloro-(4-chloro-phenyl)-(3-methyl-3H-imidazol-4-yl)-methyl]-5-(3-chloro-phenyl)-1,2,3,9b-tetraaza-cyclopenta[a]naphthalene
  参考文献：
  名称：

  Substituted azoloquinolines and -quinazolines as new potent farnesyl protein transferase inhibitors

  摘要：

  A series of (4-chlorophenyl)-alpha-(1-methyl-1H-imidazol-5-yl)azoloquinolines and -quinazolines was prepared. These compounds displayed potent Farnesyl Protein Transferase inhibitory activity and tetrazolo[1,5-a]quinazolines are promising agents for oral in vivo inhibition. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.080
• 作为产物：
  描述：

  N-[2-(3-chlorobenzoyl)-4-(4-chlorobenzoyl)phenyl]acetamide 在 正丁基锂 、 sodium azide 、 potassium tert-butylate 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 N,N-二甲基甲酰胺 为溶剂， 生成 (4-Chloro-phenyl)-[5-(3-chloro-phenyl)-1,2,3,9b-tetraaza-cyclopenta[a]naphthalen-7-yl]-(3-methyl-3H-imidazol-4-yl)-methanol
  参考文献：
  名称：

  Substituted azoloquinolines and -quinazolines as new potent farnesyl protein transferase inhibitors

  摘要：

  A series of (4-chlorophenyl)-alpha-(1-methyl-1H-imidazol-5-yl)azoloquinolines and -quinazolines was prepared. These compounds displayed potent Farnesyl Protein Transferase inhibitory activity and tetrazolo[1,5-a]quinazolines are promising agents for oral in vivo inhibition. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.080

文献信息

• 1,2-annelated quinoline derivatives
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US20030119843A1

  公开（公告）日：2003-06-26

  This invention concerns compounds of formula 1 the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein ═X 1 —X 2 —X 3 — is a trivalent radical,; >Y 1 —Y 2 — is a trivalent radical; r and s are each independently 0, 1, 2, 3, 4 or 5; t is 0, 1, 2 or 3; each R 1 and R 2 are independently hydroxy, halo, cyano, C 1-6 alkyl, trihalomethyl, trihalomethoxy, C 2-6 alkenyl, C 1-6 alkyloxy, hydroxyC 1-6 alkyloxy, C 1-6 alkylthio, C 1-6 alkyloxyC 1-6 alkyloxy, C 1-6 alkyloxycarbonyl, aminoC 1-6 alkyloxy, mono- or di(C 1-6 alkyl)amino, mono- or di(C 1-6 alkylaminoC 1-6 alkyloxy, aryl, arylC 1-6 alkyl, aryloxy or arylC 1-6 alkyloxy, hydroxycarbonyl, C 1-6 alkyloxycarbonyl; or two R 1 or R 2 on adjacent positions form together a bivalent radical; R 3 is hydrogen, halo, C 1-6 alkyl, cyano, haloC 1-6 alkyl, hydroxyC 1-6 alkyl, cyanoC 1-6 alkyl, aminoC 1-6 alkyl, C 1-6 alkyloxyC 1-6 alkyl, C 1-6 alkylthio-C 1-6 alkyl, aminocarbonylC 1-6 alkyl, hydroxycarbonyl, hydroxycarbonylC 1-6 alkyl, C 1-6 alkyoxycarbonylC 1-6 alkyl, C 1-6 alkylcarbonylC 1-6 alkyl, C 1-6 alkyloxycarbonyl, aryl, arylC 1-6 alkyloxyC 1-6 alkyl, mono- or di(C 1-6 alkyl)aminoC 1-6 alkyl, or a radical of formula —O—R 10 , —S—R 10 or —NR 11 R 12 ; R 4 is an optionally substituted imidazolyl; aryl is an optionally substituted phenyl or naphthalenyl; having farnesyl transferase and geranylgeranyl transferase inhibiting activity; their preparation, compositions containing them and their use as a medicine.

  本发明涉及公式1的化合物及其药学上可接受的酸盐和立体化学异构体，其中═X1—X2—X3—是三价基团; >Y1—Y2—是三价基团; r和s分别独立地为0、1、2、3、4或5; t为0、1、2或3; 每个R1和R2独立地为羟基、卤素、氰基、C1-6烷基、三卤甲基、三卤甲氧基、C2-6烯基、C1-6烷氧基、羟基C1-6烷氧基、C1-6烷基硫基、C1-6烷氧基C1-6烷氧基、C1-6烷氧基羰基、氨基C1-6烷氧基、单-或双(C1-6烷基)氨基、单-或双(C1-6烷基氨基C1-6烷氧基、芳基、芳基C1-6烷基、芳氧基或芳基C1-6烷氧基、羟基羧酸、C1-6烷氧羧酸; 或者相邻位置的两个R1或R2结合成一个二价基团; R3是氢、卤素、C1-6烷基、氰基、卤素C1-6烷基、羟基C1-6烷基、氰基C1-6烷基、氨基C1-6烷基、C1-6烷氧基C1-6烷基、C1-6烷基硫基-C1-6烷基、氨基羧酰基C1-6烷基、羟基羧酰基、羟基羧酰基C1-6烷基、C1-6烷氧羧酸C1-6烷基、C1-6烷基羧酰基C1-6烷基、C1-6烷氧羰基、芳基、芳基C1-6烷氧基C1-6烷基、单-或双(C1-6烷基)氨基C1-6烷基，或者是公式—O—R10、—S—R10或—NR11R12的基团; R4是可选择取代的咪唑基; 芳基是可选择取代的苯基或萘基; 具有法尼酰转移酶和戊二烯基戊二酰转移酶抑制活性; 它们的制备、含有它们的组合物以及它们作为药物的用途。
• 1,2-ANNELATED QUINOLINE DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1140935B1

  公开（公告）日：2003-05-14
• US6458800B1
  申请人：——

  公开号：US6458800B1

  公开（公告）日：2002-10-01
• US6914066B2
  申请人：——

  公开号：US6914066B2

  公开（公告）日：2005-07-05
• Substituted azoloquinolines and -quinazolines as new potent farnesyl protein transferase inhibitors
  作者：Patrick Angibaud、Xavier Bourdrez、David W. End、Eddy Freyne、Michel Janicot、Patricia Lezouret、Yannick Ligny、Geert Mannens、Siegrid Damsch、Laurence Mevellec、Christophe Meyer、Philippe Muller、Isabelle Pilatte、Virginie Poncelet、Bruno Roux、Gerda Smets、Jacky Van Dun、Pieter Van Remoortere、Marc Venet、Walter Wouters

  DOI：10.1016/j.bmcl.2003.08.080

  日期：2003.12

  A series of (4-chlorophenyl)-alpha-(1-methyl-1H-imidazol-5-yl)azoloquinolines and -quinazolines was prepared. These compounds displayed potent Farnesyl Protein Transferase inhibitory activity and tetrazolo[1,5-a]quinazolines are promising agents for oral in vivo inhibition. (C) 2003 Elsevier Ltd. All rights reserved.