3-Ethyl-9-(4-fluoro-phenyl)-7-methyl-2,3,4,4a-tetrahydro-1H-3-aza-fluorene

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚和异茚
• 英文名称: 3-Ethyl-9-(4-fluoro-phenyl)-7-methyl-2,3,4,4a-tetrahydro-1H-3-aza-fluorene
• 英文别名: 2-Ethyl-5-(4-fluorophenyl)-7-methyl-1,3,4,9b-tetrahydroindeno[1,2-c]pyridine
• 化学式: C₂₁H₂₂FN
• 分子量: 307.411
• InChiKey: DKBBYFXUQKNCOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (4aR,10aR)-2-Ethyl-5-(4-fluoro-phenyl)-7-methyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]isoquinolin-5-ol 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 3-Ethyl-9-(4-fluoro-phenyl)-7-methyl-2,3,4,4a-tetrahydro-1H-3-aza-fluorene
  参考文献：
  名称：

  Structure-Activity Studies of 2,3,4,4a,5,9b-Hexahydroindeno[1,2-c]pyridines as Antispermatogenic Agents for Male Contraception

  摘要：

  Analogs of (4aRS,5SR,9bRS)-2-ethyl-2,3,4,4a,5,9b-hexahydro-7-methyl-5-p-tolyl-1H-indeno[1,2-c]pyridine (Sandoz 20-438, 10a; R(1) = ethyl, R(2) = R(3) = methyl, R(4) = H) have been synthesized and tested in mice for their ability to reduce testes weight and disrupt spermatogenesis. The activity was strongly dependent on stereoisomerism and chirality, consistent with a mechanism of action involving interaction with a specific macromolecule. It was affected by changes in the nitrogen substituent and most strikingly by changes in the p-substituent of the 5-aryl ring. A hydrogen, fluorine, hydroxy, or methoxy substituent led to loss of activity, whereas methyl (Sandoz 20-438, 10a), carboxylate (RTI-4587-054, 10k; R(1) = ethyl, R(2) = methyl, R(3) = COOH, R(4) = H), ester (RTI-4587-056, 12b; R(1) = ethyl, R(2) = methyl, R(3) = COOMe, R(4) = H), formyl (RTI-4587-030, 12i; R(1) = ethyl, R2 = methyl, R(3) = CHO, R(4) = H), or hydroxymethyl (RTI-4587-055, 12g; R(1) = ethyl, R(2) = methyl, R(3) = CH2OH, R(4) = H) groups resulted in antispermatogenic compounds. Methyl ester 12b was an effective antifertility agent, without apparent effects on mating, when given orally to male mice at 7-15 mg/kg daily for 35 days. Further evaluation of these compounds as male contraceptive agents and probes for study of spermatogenesis appears warranted.

  DOI：

  10.1021/jm00005a003

文献信息

• Structure-Activity Studies of 2,3,4,4a,5,9b-Hexahydroindeno[1,2-c]pyridines as Antispermatogenic Agents for Male Contraception
  作者：C. Edgar Cook、Mansukh C. Wani、Joseph M. Jump、Yue-W. Lee、Patricia A. Fail、Stephanie A. Anderson、Yu-Q. Gu、Vladimir Petrow

  DOI：10.1021/jm00005a003

  日期：1995.3

  Analogs of (4aRS,5SR,9bRS)-2-ethyl-2,3,4,4a,5,9b-hexahydro-7-methyl-5-p-tolyl-1H-indeno[1,2-c]pyridine (Sandoz 20-438, 10a; R(1) = ethyl, R(2) = R(3) = methyl, R(4) = H) have been synthesized and tested in mice for their ability to reduce testes weight and disrupt spermatogenesis. The activity was strongly dependent on stereoisomerism and chirality, consistent with a mechanism of action involving interaction with a specific macromolecule. It was affected by changes in the nitrogen substituent and most strikingly by changes in the p-substituent of the 5-aryl ring. A hydrogen, fluorine, hydroxy, or methoxy substituent led to loss of activity, whereas methyl (Sandoz 20-438, 10a), carboxylate (RTI-4587-054, 10k; R(1) = ethyl, R(2) = methyl, R(3) = COOH, R(4) = H), ester (RTI-4587-056, 12b; R(1) = ethyl, R(2) = methyl, R(3) = COOMe, R(4) = H), formyl (RTI-4587-030, 12i; R(1) = ethyl, R2 = methyl, R(3) = CHO, R(4) = H), or hydroxymethyl (RTI-4587-055, 12g; R(1) = ethyl, R(2) = methyl, R(3) = CH2OH, R(4) = H) groups resulted in antispermatogenic compounds. Methyl ester 12b was an effective antifertility agent, without apparent effects on mating, when given orally to male mice at 7-15 mg/kg daily for 35 days. Further evaluation of these compounds as male contraceptive agents and probes for study of spermatogenesis appears warranted.