8-chloro-5-nitro-2-(n-propyl-N-propionylamino)-1,2,3,4-tetrahydronaphthalene | 136905-99-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 8-chloro-5-nitro-2-(n-propyl-N-propionylamino)-1,2,3,4-tetrahydronaphthalene
• 英文别名: 8-chloro-5-nitro-2-(N-n-propyl-N-propionylamino)tetralin；N-(8-chloro-5-nitro-1,2,3,4-tetrahydronaphthalen-2-yl)-N-propylpropanamide
• CAS: 136905-99-2
• 化学式: C₁₆H₂₁ClN₂O₃
• 分子量: 324.807
• InChiKey: PRJXGRAELVDCHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  66.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-chloro-5-nitro-2-(n-propyl-N-propionylamino)-1,2,3,4-tetrahydronaphthalene 在 palladium on activated charcoal ammonium formate 作用下， 以 乙醇 为溶剂， 以88%的产率得到5-amino-2-(N-n-propyl-N-propionylamino)-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  5-, 6-, 7- and 8-amino-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalenes: centrally acting DA and 5-HT1A agonists

  摘要：

  5-, 6-, 7- and 8-Amino-2-(NN-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene were synthesized and compared with the corresponding phenolic compounds in vivo and in vitro for their effects on central serotonergic (5-HT1A) and dopaminergic (D2) systems. The 5- and 8-amino isomers surprisingly showed a 100-fold lower affinity for D2 and 5-HT1A receptors, respectively, than their corresponding phenols. This was also reflected in vivo. The 6-amino- and hydroxy-isomers were equipotent, while the 7-amino compound showed in vivo effects both on dopaminergic and serotonergic systems, the latter not being noticed in vitro. Intermediates 8-bromo-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene and 2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene-8-carboxylic acid methyl ester were also tested and found to be quite potent 5-HT1A agonists.

  DOI：

  10.1016/0223-5234(93)90028-d
• 作为产物：
  描述：

  8-chloro-2-(n-propylamino)-1,2,3,4-tetrahydronaphthalene 在 硫酸 、 硝酸 、 三乙胺 作用下， 以 硝基甲烷 、 二氯甲烷 为溶剂， 反应 0.17h， 生成 8-chloro-5-nitro-2-(n-propyl-N-propionylamino)-1,2,3,4-tetrahydronaphthalene
  参考文献：
  名称：

  5-, 6-, 7- and 8-amino-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalenes: centrally acting DA and 5-HT1A agonists

  摘要：

  5-, 6-, 7- and 8-Amino-2-(NN-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene were synthesized and compared with the corresponding phenolic compounds in vivo and in vitro for their effects on central serotonergic (5-HT1A) and dopaminergic (D2) systems. The 5- and 8-amino isomers surprisingly showed a 100-fold lower affinity for D2 and 5-HT1A receptors, respectively, than their corresponding phenols. This was also reflected in vivo. The 6-amino- and hydroxy-isomers were equipotent, while the 7-amino compound showed in vivo effects both on dopaminergic and serotonergic systems, the latter not being noticed in vitro. Intermediates 8-bromo-2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene and 2-(N,N-di-n-propylamino)-1,2,3,4-tetrahydronaphthalene-8-carboxylic acid methyl ester were also tested and found to be quite potent 5-HT1A agonists.

  DOI：

  10.1016/0223-5234(93)90028-d

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.

  化合物公式I的化合物或公式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）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。公式I的化合物适用于治疗中枢神经系统的疾病，特别是作为5-HT.sub.1A受体激动剂。
• Centrally acting 6,7,8,9-tetrahydro-3H-benz(e) indole heterocyclics
  申请人：The Upjohn Company

  公开号：US05650427A1

  公开（公告）日：1997-07-22

  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.

  一种化合物I的公式 ##STR1## 或公式I的药学上可接受的盐，其中R.sup.1是H，C.sub.1-C.sub.3烷基，--(CH.sub.2).sub.n CONH.sub.2，其中n为2到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是氢，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是氢，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到5，C.dbd.NOR.sup.2，2（4,5-二氢）噁唑基，或COR.sup.10，其中R.sup.10是H，R.sup.1，NR.sup.1 R.sup.2或CF.sub.3；R.sup.4是氢，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是氢，R.sup.1，OCH.sub.3，C（O）CH.sub.3或C（O）OR.sup.1；X是（a）一个价键，（b）CH.sub.2，或（c）O，S或NR.sup.5，其中R.sup.5是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是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是氢或卤素；但是当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。公式I的化合物适用于治疗中枢神经系统的疾病，尤其是作为5-HT.sub.1A受体激动剂。
• Centrally acting 6,7,8,9-tetrahydro-3H-benz(e)indole heterocyclics
  申请人：The Upjohn Company

  公开号：US05288748A1

  公开（公告）日：1994-02-22

  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 --R"--Ar where R" 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-thienyl or 3-thienyl; 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的药物可接受的盐，其中R.sup.1是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是氢，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"是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且R.sup.9是苯基，2-噻吩基或3-噻吩基; R.sup.3是氢，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是H，R.sup.1，NR.sup.1 R.sup.2或CF.sub.3; R.sup.4是氢，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是氢，R.sup.1，OCH.sub.3，C（O）CH.sub.3或C（O）OR.sup.1; X是（a）一个价键，（b）CH.sub.2，或（c）O，S或NR.sup.5，其中R.sup.5是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是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是氢或卤素; 前提是当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。公式I的化合物适用于治疗中枢神经系统的疾病，特别是作为5-HT.sub.1A受体激动剂。
• (S)- and (R)-8-(di-n-propylamino)-6,7,8,9-tetrahydro-3H-benz[e]indole-1-carbaldehyde: a new class of orally active 5-HT1A-receptor agonists
  作者：Peter Stjernloef、Maria Gullme、Thomas Elebring、Bengt Andersson、Haakan Wikstroem、Soeren Lagerquist、Kjell Svensson、Agneta Ekman、Arvid Carlsson、Staffan Sundell

  DOI：10.1021/jm00067a002

  日期：1993.7

  The enantiomers of 6,7,8,9-tetrahydro-N,N-di-n-propyl-3H-benz[e]indol-8-amine (S-(-)-2b and R-(+)-2b) and their corresponding 1-formyl analogs (S-(-)-6 and R-(+)-6) were prepared and evaluated pharmacologically for serotonergic and dopaminergic activity. The introduction of a formyl group in the 1-position shifted the pharmacological profile of 2b from a mixed D2/5-HT1A agonists to a selective 5-HT1A agonist (6). The enantiomers of 6 were agonists with full intrinsic activity and had an affinity comparable to that of 8-hydroxy-2-(di-n-propylamino)tetrahydronaphthalene (8-OH-DPAT). In contrast to 8-OH-DPAT, the enantiomers of compound 6 were found to have good oral availability.
• 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