(4AR)-(10BR)-4,10b-dimethyl-8-allyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one | 176976-36-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (4AR)-(10BR)-4,10b-dimethyl-8-allyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one
• 英文别名: (4aR,10bR)-4,10b-dimethyl-8-prop-2-enyl-2,4a,5,6-tetrahydro-1H-benzo[f]quinolin-3-one
• CAS: 176976-36-6
• 化学式: C₁₈H₂₃NO
• 分子量: 269.387
• InChiKey: LMGNRNKZJXEILM-SJLPKXTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (4AR)-(10BR)-4,10b-dimethyl-8-allyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one 在 ruthenium trichloride 、 sodium periodate 作用下， 生成 (+)-(4AR)-(10BR)-4-methyl-8-carboxy-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one 、 (4AR)-(10BR)-4,10b-dimethyl-8-carboxymethyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one
  参考文献：
  名称：

  Synthesis and 5α-reductase inhibitory activity of 8-substituted benzo[ƒ]quinolinones derived from palladium mediated coupling reactions

  摘要：

  Benzoquinolinones have been shown to be potent, selective inhibitors of the Type I 5 alpha-reductase enzyme, which is responsible for the production of dihydrotestosterone from testosterone localized in the scalp. In an effort to identify compounds that demonstrate inhibition of both 5 alpha-reductase isozymes, we have employed 8-bromobenzoquinolinone as an advanced intermediate for participation in a variety of palladium mediated carbon-carbon bond forming reactions. By varying the 8-substituent it is possible to alter the selectivity profile of the series. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00035-3
• 作为产物：
  描述：

  烯丙基三丁基锡 、 (+)-(4aR)-(10bR)-4-methyl-8-bromo-10b-methyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one 在 四(三苯基膦)钯 作用下， 以90%的产率得到(4AR)-(10BR)-4,10b-dimethyl-8-allyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one
  参考文献：
  名称：

  Synthesis and 5α-reductase inhibitory activity of 8-substituted benzo[ƒ]quinolinones derived from palladium mediated coupling reactions

  摘要：

  Benzoquinolinones have been shown to be potent, selective inhibitors of the Type I 5 alpha-reductase enzyme, which is responsible for the production of dihydrotestosterone from testosterone localized in the scalp. In an effort to identify compounds that demonstrate inhibition of both 5 alpha-reductase isozymes, we have employed 8-bromobenzoquinolinone as an advanced intermediate for participation in a variety of palladium mediated carbon-carbon bond forming reactions. By varying the 8-substituent it is possible to alter the selectivity profile of the series. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00035-3

文献信息

• Method of preventing prostatic cancer development
  申请人：ELi Lilly and Company

  公开号：US05629007A1

  公开（公告）日：1997-05-13

  A series of benzoquinolin-3-ones are pharmaceuticals effective in preventing the development of prostatic cancer, or preventing or treating the metastasis to bone of prostatic cancer.

  一系列苯并喹啉-3-酮是一种有效的药物，可预防前列腺癌的发展，或预防或治疗前列腺癌转移到骨骼。
• Treatment and prevention of prostatic cancer metastasis
  申请人：Eli Lilly and Company

  公开号：US05635197A1

  公开（公告）日：1997-06-03

  A series of benzoquinolin-3-ones are pharmaceuticals effective in preventing the development of prostatic cancer, or preventing or treating the metastasis to bone of prostatic cancer.

  一系列苯并喹啉-3-酮是有效的药物，可预防前列腺癌的发展，或预防或治疗前列腺癌转移到骨骼。
• Methods for inhibiting bone loss
  申请人：Eli Lilly and Company

  公开号：US05550134A1

  公开（公告）日：1996-08-27

  The present invention provides methods of inhibiting bone loss in mammals via the administration to a mammal in need of such treatment an effective amount of a compound from a series of benzoquinolin-3-ones. Such compounds also are sequentially or concurrently coadministered with a bone antiresorptive agent or a bone anabolic agent.

  本发明提供了通过向需要此类治疗的哺乳动物施用一系列苯并喹啉-3-酮化合物的有效量来抑制哺乳动物的骨丢失的方法。这些化合物也可与骨抗吸收剂或骨促进剂顺序或同时联合使用。
• Compositions for inhibiting bone loss
  申请人：Eli Lilly and Company

  公开号：US05670514A1

  公开（公告）日：1997-09-23

  The present invention provides methods of inhibiting bone loss in mammals via the administration to a mammal in need of such treatment an effective amount of a compound from a series of benzoquinolin-3-ones. Such compounds also are sequentially or concurrently coadministered with a bone antiresorptive agent or a bone anabolic agent.

  本发明提供了一种通过向需要此类治疗的哺乳动物施用一系列苯并喹啉-3-酮类化合物的有效剂量来抑制哺乳动物骨质流失的方法。这些化合物也可以顺序或同时与骨抗吸收剂或骨阳性剂联合使用。
• 5 alpha-reductase Inhibitors
  申请人：ELI LILLY AND COMPANY

  公开号：EP0703221A1

  公开（公告）日：1996-03-27

  A series of benzoquinolin-3-ones are pharmaceuticals effective in treating conditions consequent on both Type I and Type II 5α -reductase. The compounds have the formula wherein R and R¹ both represent hydrogen or combine to form a bond;    R represents hydrogen or C₁-C₃ alkyl;    R³ represents methyl or ethyl;    R⁴ and -X-R⁵ each occupies one of the 7-, 8-and 9-positions;    R⁴ represents hydrogen, halo, methyl or ethyl;    X represents C₁-C₄ alkyl, C₂-C₄ alkenyl, C₂-C₄ alkynyl, a bond, -SO-, -SO₂-, -CO-Y-(CH₂)n-, -Y-CO-(CH₂)n, -CO-, -Z-(CH₂)n-, or -SO₃-; wherein X groups which are not symmetrical may be in either orientation;    Y represents -S-, -O-, or -NH-;    Z represents -O- or -S-;    n represents 0-3;    R⁵ represents phenyl, naphthalenyl, pyridinyl, pyrazinyl, pyridazinyl, pyrimidinyl, anthracenyl, acenaphthalenyl, thiazolyl, benzimidazolyl, indazolyl, thiophenyl, phenanthrenyl, quinolinyl, fluorenyl, isoquinolinyl, indanyl, benzopyranyl, indolyl, benzisoquinolinyl, benzindolyl, benzothiazolyl, benzothiophenyl, quinoxalinyl, benzoxazolyl, tetrazolyl, naphthothiazolyl, quinazolinyl, thiazolopyridinyl, pyridazinoquinazolinyl, benzisothiazolyl, benzodioxolyl, benzodioxinyl, diphenylmethyl or triphenylmethyl;    the above R⁵ groups are unsubstituted or substituted with 1-3 groups chosen from the group consisting of halo, trifluoromethyl, trifluoroethoxy, C₁-C₄ alkyl, trifluoromethoxy, hydroxy, C₁-C₃ alkoxy, nitro, C₁-C₃ alkylthio, C₁-C₆ alkanoyl, phenyl, oxo, phenoxy, phenylthio, C₁-C₃ alkylsulfinyl, C₁-C₃ alkylsulfonyl, cyano, amino, C₁-C₃ alkylamino, diphenylmethylamino, triphenylmethylamino, benzyloxy, benzylthio, (mono-halo, nitro or CF₃)benzyl(oxy or thio), di(C₁-C₃ alkyl, C₃-C₆ cycloalkyl, or C₄-C₈ cycloalkylalkyl)amino, (mono-C₁-C₃ alkyl, C₁-C₃ alkoxy or halo)-(phenyl, phenoxy, phenylthio, phenylsulfonyl or phenoxysulfonyl), C₂-C₆ alkanoylamino, benzoylamino, diphenylmethylamino(C₁-C₃ alkyl), aminocarbonyl, C₁-C₃ alkylaminocarbonyl, di(C₁-C₃ alkyl)aminocarbonyl, halo-C₁-C₆ alkanoyl, aminosulfonyl, C₁-C₃ alkylaminosulfonyl, di(C₁-C₃ alkyl)aminosulfonyl, phenyl(oxy or thio)(C₁-C₃ alkyl), (halo, C₁-C₃ alkyl or C₁-C₃ alkoxy)phenyl(oxy or thio) (C₁-C₃ alkyl), benzoyl, or (amino, C₁-C₃ alkylamino or di(C₁-C₃ alkyl)amino)(C₁-C₃ alkyl);    or an above R⁵ group is substituted with a morpholino(C₁-C₃ alkyl) group, a phenyl(C₁-C₃ alkyl)piperidinyl group, a phenyl(C₁-C₃ alkyl)-Piperidinylaminocarbonyl group, a C₂-C₆ alkanoylaminothiophenyl group, or a (amino, C₁-C₃ alkylamino or di(C₁-C₃ alkyl)amino)naphthalenylsulfonylamino group;    or R⁵ is a perhalophenyl group;    or a pharmaceutically acceptable salt thereof.

  一系列苯并喹啉-3-酮类化合物是治疗 I 型和 II 型 5α 还原酶所致疾病的有效药物。这些化合物的化学式为 其中 R 和 R¹ 均代表氢或结合成键； R 代表氢或 C₁-C₃ 烷基； R³ 代表甲基或乙基； R⁴ 和 -X-R⁵ 各占 7、8 和 9 位中的一个； R⁴ 代表氢、卤素、甲基或乙基； X 代表 C₁-C₄ 烷基、C₂-C₄ 烯基、C₂-C₄ 炔基、键、-SO-、-SO₂-、-CO-Y-(CH₂)n-、-Y-CO-(CH₂)n-、-CO-、-Z-(CH₂)n- 或-SO₃-；其中非对称的 X 基团可以是任一取向； Y 代表-S-、-O-或-NH-； Z 代表-O-或-S-； n 代表 0-3； R⁵ 代表苯基、萘基、吡啶基、吡嗪基、哒嗪基、嘧啶基、蒽基、苊烯基、噻唑基、苯并咪唑基、吲唑基、噻吩基、菲基、喹啉基、芴基、异喹啉基、茚基、苯并吡喃基、吲哚基苯并异喹啉基、苯并吲哚基、苯并噻唑基、苯并噻吩基、喹喔啉基、苯并噁唑基、四唑基、萘并噻唑基、喹唑啉基、噻唑并吡啶基、哒嗪并喹唑啉基、苯并异噻唑基、苯并二噁唑基、苯并二噁嗪基、二苯基甲基或三苯甲基； 上述 R⁵ 基团未被取代或被 1-3 个基团取代，这些基团选自卤代、三氟甲基三氟乙氧基、C₁-C₄ 烷基、三氟甲氧基、羟基、C₁-C₃ 烷氧基、硝基、C₁-C₃ 烷硫基、C₁-C₆ 烷酰基、苯基、氧代、苯氧基C₁-C₃烷基硫基、C₁-C₃烷基磺酰基、氰基、氨基、C₁-C₃烷基氨基、二苯基甲基氨基、三苯基甲基氨基、苄氧基、苄硫基、（单卤代、硝基或 CF₃）苄基（氧基或硫代）、二（C₁-C₃ 烷基、C₃-C₆ 环烷基或 C₄-C₈环烷基烷基）氨基、(单-C₁-C₃烷基、C₁-C₃烷氧基或卤代)-(苯基、苯氧基、苯硫基、苯磺酰基或苯氧基磺酰基)、C₂-C₆烷酰氨基、苯甲酰氨基、二苯基甲基氨基（C₁-C₃ 烷基），氨基羰基，C₁-C₃ 烷基氨基羰基，二（C₁-C₃ 烷基）氨基羰基，卤代-C₁-C₆ 烷酰基、氨基磺酰基、C₁-C₃ 烷基氨基磺酰基、二(C₁-C₃ 烷基)氨基磺酰基、苯基(氧基或硫代)(C₁-C₃ 烷基)、(卤代、C₁-C₃烷基或C₁-C₃烷氧基)苯基(氧基或硫代)(C₁-C₃烷基)、苯甲酰基或(氨基、C₁-C₃烷基氨基或二(C₁-C₃烷基)氨基)(C₁-C₃烷基)； 或上述 R⁵ 基团被吗啉基(C₁-C₃烷基)、苯基(C₁-C₃烷基)哌啶基、苯基(C₁-C₃烷基)-哌啶氨基羰基取代、C₂-C₆烷酰氨基噻吩基团，或 (氨基、C₁-C₃烷基氨基或二(C₁-C₃烷基)氨基)萘磺酰氨基基团； 或 R⁵ 是高卤苯基； 或其药学上可接受的盐。