1-Cyano-6,7,8,9-tetrahydro-N,N-dipropyl-8-amino-3H-benz[e]indole

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-Cyano-6,7,8,9-tetrahydro-N,N-dipropyl-8-amino-3H-benz[e]indole
• 英文别名: 8-Dipropylamino-6,7,8,9-tetrahydro-3H-benzo[e]indole-1-carbonitrile；8-(dipropylamino)-6,7,8,9-tetrahydro-3H-benzo[e]indole-1-carbonitrile
• 化学式: C₁₉H₂₅N₃
• 分子量: 295.428
• InChiKey: ODCNQSRYNGLVNW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  42.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  邻氯苯乙酸 在 AlCl₃ 盐酸 、 氯化亚砜 、 NaHSO₄ 作用下， 以 N-甲基乙酰胺 、 甲醇 、 乙醇 、 二氯甲烷 、 氨 、 水 、 乙腈 为溶剂， 生成 1-Cyano-6,7,8,9-tetrahydro-N,N-dipropyl-8-amino-3H-benz[e]indole
  参考文献：
  名称：

  Centrally acting 6,7,8,9-tetrahydro-3H-benz(e)indole heterocyclics

  摘要：

  Formula I的化合物或Formula I的药学上可接受的盐，其中R.sup.1为H，C.sub.1-C.sub.3烷基，--(CH.sub.2).sub.n CONH.sub.2，其中n为2至6，(CH2).sub.n-1-(4,4-二甲基哌啶-2,6-二酮基)，或环丙甲基；R.sup.2为氢，C.sub.1-C.sub.8烷基，C.sub.3-C.sub.8环烷基或与R.sup.1结合形成C.sub.3-C.sub.8环烷基，C.sub.2-C.sub.8烯基，C.sub.2-C.sub.8炔基，(CH.sub.2).sub.n--R"--Ar，其中R"为O，S或NH，3,3,3-三氟丙基，--(CH.sub.2).sub.m--R.sup.9，其中m为2或3，R.sup.9为苯基、2-噻吩基或3-噻吩基；R.sup.3为氢，C.sub.1-C.sub.3烷基，2,2,2-三氟乙基，3,3,3-三氟丙基，甲酰基，CN，卤素，CH.sub.2OR.sup.2，C(O)C(O)OR.sup.1，C(O)CO NR.sup.1 R.sup.2，--(CH.sub.2).sub.q--NR.sup.1 R.sup.2，其中q为0至5，C.dbd.NOR.sup.2，2(4,5-二氢)噁唑基，或COR.sup.10，其中R.sup.10为H，R.sup.1，NR.sup.1 R.sup.2或CF.sub.3；R.sup.4为氢，C.sub.1-C.sub.3烷基，环丙甲基，CF.sub.3，2,2,2-三氟乙基，CN，CONR.sup.1 R.sup.2，.dbd.O，2(4,5-二氢)咪唑基，2(4,5-二氢)噁唑基，2-噁唑基，3-噁二唑基，或3,3,3-三氟丙基；R.sup.5为氢，R.sup.1，OCH.sub.3，C(O)CH.sub.3或C(O)OR.sup.1；X为(a)一个价键，(b)CH.sub.2，或(c)O，S或NR.sup.5，其中R.sup.5为H，C.sub.1-C.sub.8烷基，C.sub.3-C.sub.8环烷基，苄基，COR.sup.6，其中R.sup.6为C.sub.1-C.sub.3烷基，苯基，或CONR.sup.7 R.sup.8，其中R.sup.7和R.sup.8独立地为H或C.sub.1-C.sub.3烷基；Z为氢或卤素；但当X为CH.sub.2时，R.sub.3和R.sub.4中至少有一个不是氢或C.sub.1-C.sub.3烷基。Formula I的化合物适用于治疗中枢神经系统疾病，特别是作为5-HT.sub.1A受体激动剂。

  公开号：

  US05288748A1

文献信息

• Centrally acting 6,7,8,9-tetrahydro-3H-benz(E)indole heterocyclics
  申请人：——

  公开号：US05461061A1

  公开（公告）日：1995-10-24

  A compound of Formula I ##STR1## or pharmaceutically acceptable salts of Formula I, where R.sup.1 is H, C.sub.1 -C.sub.3 alkyl, --(CH.sub.2).sub.n CONH.sub.2 where n is 2 to 6, (CH2).sub.n -1-(4,4-dimethylpiperidine-2,6-dione-yl), or cyclopropylmethyl; R.sup.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl or combined with R.sup.1 to form a C.sub.3 -C.sub.8 cycloalkyl, C.sub.2 -C.sub.8 alkenyl, C.sub.2 -C.sub.8 akynyl, (CH.sub.2).sub.n --X--Ar where X is O, S, or NH, 3,3,3-trifluoropropyl, --(CH.sub.2).sub.m --R.sup.9 where m is 2 or 3 and R.sup.9 is phenyl, 2-thiophenyl or 3-thiophenyl; R.sup.3 is hydrogen, C.sub.1 -C.sub.3 alkyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, formyl, CN, halogen, CH.sub.2 OR.sup.2, C(O)C(O)OR.sup.1, C(O)CO NR.sup.1 R.sup.2, --(CH.sub.2).sub.q --NR.sup.1 R.sup.2 where q is 0 to 5, C.dbd.NOR.sup.2, 2(4,5-dihydro)oxazolyl, or COR.sup.10 where R.sup.10 is H, R.sup.1, NR.sup.1 R.sup.2 or CF.sub.3 ; R.sup.4 is hydrogen, C.sub.1 -C.sub.3 alkyl, cyclopropylmethyl, CF.sub.3, 2,2,2-trifluoroethyl, CN, CONR.sup.1 R.sup.2, .dbd.O, 2(4,5-dihydro)imidazolyl, 2(4,5-dihydro)oxazolyl, 2-oxazolyl, 3-oxadiazolyl, or 3,3,3-trifluoropropyl; R.sup.5 is hydrogen, R.sup. 1, OCH.sub.3, C(O)CH.sub.3 or C(O)OR.sup.1 ; X is (a) a valence bond, (b) CH.sub.2, or (c) O, S or NR.sup.5 where R.sup.5 is H, C.sub.1 -C.sub.8 alkyl, C.sub.3 -C.sub.8 cycloalkyl, benzyl, COR.sup.6 where R.sup.6 is a C.sub.1 -C.sub.3 alkyl, phenyl, or CONR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 are independently H or C.sub.1 -C.sub.3 alkyl; and Z is a hydrogen or halogen; provided that when X is CH.sub.2, at least one of R.sub.3 and R.sub.4 is other than hydrogen or C.sub.1 -C.sub.3 alkyl. The compounds of Formula I are suitable for treating disorders of the central nervous system, particularly as 5-HT.sub.1A receptor agonists.

  公式I的化合物##STR1##或公式I的药用盐，其中R.sup.1为H、C.sub.1 -C.sub.3烷基、--(CH.sub.2).sub.n CONH.sub.2，其中n为2至6，(CH2).sub.n-1-(4,4-二甲基哌啶-2,6-二酮基)或环丙基甲基；R.sup.2为氢、C.sub.1 -C.sub.8烷基、C.sub.3 -C.sub.8环烷基或与R.sup.1结合形成C.sub.3 -C.sub.8环烷基、C.sub.2 -C.sub.8烯基、C.sub.2 -C.sub.8炔基、(CH.sub.2).sub.n--X--Ar，其中X为O、S或NH、3,3,3-三氟丙基、--(CH.sub.2).sub.m--R.sup.9，其中m为2或3，R.sup.9为苯基、2-噻吩基或3-噻吩基；R.sup.3为氢、C.sub.1 -C.sub.3烷基、2,2,2-三氟乙基、3,3,3-三氟丙基、甲酰基、CN、卤素、CH.sub.2 OR.sup.2、C(O)C(O)OR.sup.1、C(O)CO NR.sup.1 R.sup.2、--(CH.sub.2).sub.q--NR.sup.1 R.sup.2，其中q为0至5、C.dbd.NOR.sup.2、2(4,5-二氢)噁唑基或COR.sup.10，其中R.sup.10为H、R.sup.1、NR.sup.1 R.sup.2或CF.sub.3；R.sup.4为氢、C.sub.1 -C.sub.3烷基、环丙基甲基、CF.sub.3、2,2,2-三氟乙基、CN、CONR.sup.1 R.sup.2、.dbd.O、2(4,5-二氢)咪唑基、2(4,5-二氢)噁唑基、2-噁唑基、3-噁二唑基或3,3,3-三氟丙基；R.sup.5为氢、R.sup. 1、OCH.sub.3、C(O)CH.sub.3或C(O)OR.sup.1；X为(a)一个价键、(b)CH.sub.2或(c)O、S或NR.sup.5，其中R.sup.5为H、C.sub.1 -C.sub.8烷基、C.sub.3 -C.sub.8环烷基、苄基、COR.sup.6，其中R.sup.6为C.sub.1 -C.sub.3烷基、苯基或CONR.sup.7 R.sup.8，其中R.sup.7和R.sup.8独立地为H或C.sub.1 -C.sub.3烷基；Z为氢或卤素；但当X为CH.sub.2时，R.sub.3和R.sub.4中至少一个不是氢或C.sub.1 -C.sub.3烷基。公式I的化合物适用于治疗中枢神经系统疾病，特别是作为5-HT.sub.1A受体激动剂。
• 6,7,8,9-Tetrahydro-N,N-di-n-propyl-3H-benzindol-8-amines. Derivatives as Potent and Orally Active Serotonin 5-HT1A Receptor Agonists
  作者：Peter Stjernloef、Thomas Elebring、Jonas Nilsson、Bengt Andersson、Soeren Lagerkvist、Kjell Svensson、Agneta Ekman、Arvid Carlsson、Haakan Wikstroem

  DOI：10.1021/jm00046a010

  日期：1994.9

  Derivatives and isosteric derivatives of the potent 5-HT1A agonist 8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole- 1-carbaldehyde (5) were prepared and evaluated in vivo and in vitro for serotonergic and dopaminergic activity. The 1-cyano analog 8 was found to be almost equipotent to 5 and the previously described 2-cyano derivative 6, while a I-chloro and 1-(1,1,1-trifluoroethyl) substituent (9 and 10, respectively) formed less potent derivatives. The isosteric 6,7,8,9-tetrahydro-1H-benz[g]indoles 4 and 12-15 showed surprisingly low affinity or activity at both serotonergic and dopaminergic systems. The interpretations of these results by means of drug-receptor interactions at the 5-HT1A subtype are discussed. Compounds 6 and 8 were found to have high oral bioavailability in the rat (63% and 54%, respectively).
• Stjernloef Peter, Elebring Thomas, Nilsson Jonas, Andersson Bengt, Lagerk+, J. Med. Chem, 37 (1994) N 20, S 3263-3273
  作者：Stjernloef Peter, Elebring Thomas, Nilsson Jonas, Andersson Bengt, Lagerk+

  DOI：——

  日期：——
• NEW CENTRALLY ACTING 6,7,8,9-TETRAHYDRO-3H-BENZ(e)INDOLE HETEROCYCLICS
  申请人：THE UPJOHN COMPANY

  公开号：EP0510068A1

  公开（公告）日：1992-10-28
• 5 HT RECEPTOR MEDIATED NEUROGENESIS
  申请人：Barlow Carrolee

  公开号：US20100009983A1

  公开（公告）日：2010-01-14

  The instant disclosure describes methods for treating diseases and conditions of the central and peripheral nervous system by stimulating or increasing neurogenesis. The disclosure includes compositions and methods based on use of a 5HTR agent, in combination with one or more other neurogenic agents, or anti-astrogenic agent, to stimulate or activate the formation of new nerve cells.