(4aS,9R,9aS)-3,7-Dimethyl-9-p-tolyl-2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorene

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (4aS,9R,9aS)-3,7-Dimethyl-9-p-tolyl-2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorene
• 英文别名: (4aS,5R,9bS)-2,7-dimethyl-5-(4-methylphenyl)-1,3,4,4a,5,9b-hexahydroindeno[1,2-c]pyridine
• 化学式: C₂₁H₂₅N
• 分子量: 291.436
• InChiKey: KWOCRVIFXSYJRP-NRSPTQNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (4aS,9R,9aS)-3,7-Dimethyl-9-p-tolyl-2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorene 在 氢氧化钾 、 氯甲酸乙酯 作用下， 生成 (4aRS,5SR,9bRS)-2,3,4,4a,5,9b-hexahydro-7-methyl-5-(4-methylphenyl)-1H-indeno<1,2-c>pyridine
  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
• 作为产物：
  描述：

  (4aR,9R,9aR)-3,7-Dimethyl-9-p-tolyl-2,3,4,4a,9,9a-hexahydro-1H-3-aza-fluorene; hydrochloride 在 氢氧化钾 作用下， 以 正丁醇 为溶剂， 生成 (4aS,9R,9aS)-3,7-Dimethyl-9-p-tolyl-2,3,4,4a,9,9a-hexahydro-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

• SPERMICIDAL AND/OR ANTIFUNGAL COMPOSITION AND METHODS OF USING THE SAME
  申请人：Cook Clarence Edgar

  公开号：US20090149490A1

  公开（公告）日：2009-06-11

  Hexahydroindenopyridine compounds are provided which act as spermicides and/or fungicides, spermicidal and/or fungicidal compositions containing the same, and methods for killing motile sperm and/or fungi using the compounds and compositions.

  提供了六氢吲哚吡啶化合物，可作为杀精剂和/或杀真菌剂，含有该化合物的杀精剂和/或杀真菌剂组合物，以及使用该化合物和组合物杀死活动精子和/或真菌的方法。
• US7544696B2
  申请人：——

  公开号：US7544696B2

  公开（公告）日：2009-06-09
• US8193213B2
  申请人：——

  公开号：US8193213B2

  公开（公告）日：2012-06-05
• 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.