3-(N-n-propyl-N-propionylamino)-3,4-dihydro-2H-[1]benzopyran | 136906-11-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3-(N-n-propyl-N-propionylamino)-3,4-dihydro-2H-[1]benzopyran
• 英文别名: 3-(N-propionyl-N-n-propylamino)chroman；N-(3,4-dihydro-2H-chromen-3-yl)-N-propylpropanamide
• CAS: 136906-11-1
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: RXCJULSAWXAJQA-UHFFFAOYSA-N

物化性质

• 沸点：
  390.8±32.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(N-n-propyl-N-propionylamino)-3,4-dihydro-2H-[1]benzopyran 在 sodium hydroxide 、 LiAlH4 、 硝酸 、 锌 作用下， 以 乙醚 、 硝基甲烷 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 生成 6-amino-3-(N,N-di-n-propylamino)-3,4-dihydro-2H-[1]benzopyran
  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
• 作为产物：
  描述：

  3-propionylamino-chroman-4-one 在 10percent Pd/C lithium aluminium tetrahydride 、 氢气 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 3-(N-n-propyl-N-propionylamino)-3,4-dihydro-2H-[1]benzopyran
  参考文献：
  名称：

  Thiazoloindans and Thiazolobenzopyrans:  A Novel Class of Orally Active Central Dopamine (Partial) Agonists

  摘要：

  The 2-aminothiazole moiety has proven its value in medicinal chemistry as a stable and lipophilic bioisosteric replacement of a phenol group. This approach has provided dopamine (DA) agonists with good oral availability. To further explore its use in the development of DA agonists, we have combined the 2-aminothiazole moiety with 2-aminoindans and 3-aminobenzopyrans, which are known templates for DA agonists. In this study we have synthesized 6-amino-3-(N,N-di-n-propylamino)-3,4-dihydro-2H-thiazole[5,4-f]-[1]benzopyran (12) and 6-amino-2-(N,N-di-n-propylamino)thiazolo[4,5-f]indan (20) and several analogues (13, 17, and 21). The affinity of the thiazolobenzopyrans and thiazoloindans for DA receptors was evaluated, which revealed compound 20 to have high affinity for DA DQ receptors. In addition, the compounds were screened for their potential to inhibit lipid peroxidation, to determine their radical scavenging properties. Compounds 12, 20, and 21 were subjected to further pharmacological evaluation in a functional assay to determine intrinsic activity. Compound 20 was also studied with microdialysis (to determine effects on DA turnover in striatum) and in unilaterally 6-OH-DA lesioned rats (to determine their potential as DA agonists). These studies selected compound 20 (GMC 1111) as particularly interesting. Compound 20 caused a rotation activation in unilaterally B-OH-DA lesioned rats and an increase in DA turnover in rat striatum. This dual agonist/antagonist action is best accounted for by its partial agonism at striatal DA D-2 receptors. Interestingly, 20 displayed long-lasting activity and excellent oral availability in B-OH-DA lesioned rats, making this compound potentially useful for the treatment of Parkinson's disease.

  DOI：

  10.1021/jm000087z

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。
• 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。
• 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
• INDOLETETRALINS HAVING DOPAMINERGIC ACTIVITY
  申请人：THE UPJOHN COMPANY

  公开号：EP0690843A1

  公开（公告）日：1996-01-10
• US5288748A
  申请人：——

  公开号：US5288748A

  公开（公告）日：1994-02-22