2-methylthieno[3,2-c][1]benzazepine-4(5H)-one | 71576-93-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2-methylthieno[3,2-c][1]benzazepine-4(5H)-one
• 英文别名: 2-methyl-4,9-dihydro-3-thia-9-azabenzo[f]azulen-10-one；2-Methyl-4,9-dihydro-3-thia-9-aza-benzo[f]azulen-10-one；2-methyl-5,10-dihydrothieno[3,2-c][1]benzazepin-4-one
• CAS: 71576-93-7
• 化学式: C₁₃H₁₁NOS
• 分子量: 229.302
• InChiKey: IHWCLXSXACICHM-UHFFFAOYSA-N

物化性质

• 熔点：
  218-221 °C(Solv: acetone (67-64-1))
• 沸点：
  320.1±31.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  57.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-methylthieno[3,2-c][1]benzazepine-4(5H)-one 在 sodium tetrahydroborate 、 potassium permanganate 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 5.5h， 生成 10-hydroxy-2-methyl-4-(4-methylpiperazin-1-yl)thieno[3,2-c][1]benzazepine
  参考文献：
  名称：

  苯并[5,6]环庚[1,2-b]噻吩和噻吩并[3,2-c]苯并氮杂衍生物的合成

  摘要：

  2-甲基-4-(4-甲基哌嗪-1-基)-10H-苯并[5,6]环庚[1,2-b]噻吩(5)和2-甲基-4-(4-)新系列甲基哌嗪-1-基)噻吩并[3,2-c][1]苯并氮杂衍生物6b-f是由2-甲基噻吩和邻苯二甲酸酐合成的。关键中间体2-甲基-4,5-二氢-10H-苯并[5,6]环庚[1,2-b]噻吩-4-酮(12)和2-甲基噻吩[3,2-c]的制备[1]苯并氮杂-4(5H),10-二酮(16)分别通过苯乙酸11的分子内脱水和异氰酸酯14的路易斯酸相关环化进行。

  DOI：

  10.1055/s-2002-20033
• 作为产物：
  描述：

  5-甲基-2-噻吩羰基苯甲酸 在 ammonium hydroxide 、 三氯化铝 、 sodium azide 、 copper(II) sulfate 、 三乙胺 、 锌 作用下， 以 邻二氯苯 、 丙酮 为溶剂， 反应 10.5h， 生成 2-methylthieno[3,2-c][1]benzazepine-4(5H)-one
  参考文献：
  名称：

  苯并[5,6]环庚[1,2-b]噻吩和噻吩并[3,2-c]苯并氮杂衍生物的合成

  摘要：

  2-甲基-4-(4-甲基哌嗪-1-基)-10H-苯并[5,6]环庚[1,2-b]噻吩(5)和2-甲基-4-(4-)新系列甲基哌嗪-1-基)噻吩并[3,2-c][1]苯并氮杂衍生物6b-f是由2-甲基噻吩和邻苯二甲酸酐合成的。关键中间体2-甲基-4,5-二氢-10H-苯并[5,6]环庚[1,2-b]噻吩-4-酮(12)和2-甲基噻吩[3,2-c]的制备[1]苯并氮杂-4(5H),10-二酮(16)分别通过苯乙酸11的分子内脱水和异氰酸酯14的路易斯酸相关环化进行。

  DOI：

  10.1055/s-2002-20033

文献信息

• [EN] SUBSTITUTED PIPERAZINES OF AZEPINES, OXAZEPINES, AND THIAZEPINES<br/>[FR] PIPERAZINES SUBSTITUTEES D'AZEPINES, D'OXAZEPINES, ET DE THIAZEPINES
  申请人：LILLY CO ELI

  公开号：WO2005026177A1

  公开（公告）日：2005-03-24

  Described herein are antipyschotic compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; R1 is hydrogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, or (C1-4) alkyl, wherein the (C1-4) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH2CH2OH, -CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C1-4) alkyl; R2 is H, halogen, (C1-6) fluoroalkyl, (C3-6) cycloalkyl, OR6, SR6, NO2, CN, COR6, C(O)OR6, C(OH)R6, CONR7R8, phenyl or (C1-6) alkyl, wherein the (C1-6) alkyl is unsubstituted or substituted with a hydroxy; R3 is hydrogen, (C 1-6)fluoroalkyl , (C3-6) cycloalkyl, (C 2-6) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C1-4)alkyl wherein (C1-4) alkyl is unsubstituted or substituted with a phenyl; R4 and R5 are independently selected from hydrogen, halogen, (C1-6) alkyl, (C1-6) fluoroalkyl, OR9, SR9, NO2, CN, or COR9; R6 is hydrogen, (C1-6) fluoroalkyl, or (C1-6) alkyl; R7 and R8 are independently hydrogen, or (C1-6) alkyl; R9 is hydrogen, (C1-6) fluoroalkyl, (C1-6) alkyl; Alk is (C1-4) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO2, or a bond; X is CH2, C=O, S, O, or SO2; Z is hydrogen, halogen, (C1-6) alkyl, (C1-6)fluoroalkyl, -OH, (C1-6) alkoxy, (C1-6) fluoroalkoxy, (C1-6) alkylthio, (C1-6) acyl, (C1-4)alkylsulfonyl, -OCF3, -NO2, - CN, carboxamido which may be substituted on the nitrogen by one or two (C1-4) alkyl groups, and -NH2 in which one of the hydrogens may be replaced by a (C1-4) alkyl group and the other hydrogen may be replaced by either a (C1-4) alkyl group, a (C1-6) acyl group, or a (C1-4) alkylsulfonyl group; the phenyl of R1, R2 or R3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R3 is unsubstituted or substituted with one to three substituents independently selected from Z; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

  本文描述了式(I)的抗精神病化合物，其中：是一个可选的苯并五元或六元芳香环，其中含有零至三个异原子，独立选择自N、O和S；R1是氢，(C1-6)氟烷基，(C3-6)环烷基，或(C1-4)烷基，其中(C1-4)烷基未取代或取代为羟基、甲氧基、乙氧基、OCH2CH2OH、-CN、咪唑烷-2-酮、苯基或四氮唑，其中四氮唑未取代或取代为(C1-4)烷基；R2是H、卤素、(C1-6)氟烷基、(C3-6)环烷基、OR6、SR6、NO2、CN、COR6、C(O)OR6、C(OH)R6、CONR7R8、苯基或(C1-6)烷基，其中(C1-6)烷基未取代或取代为羟基；R3是氢，(C1-6)氟烷基，(C3-6)环烷基，(C2-6)烯基，苯基，单环杂芳基，双环杂芳基，或(C1-4)烷基，其中(C1-4)烷基未取代或取代为苯基；R4和R5独立选择自氢、卤素、(C1-6)烷基、(C1-6)氟烷基、OR9、SR9、NO2、CN或COR9；R6是氢、(C1-6)氟烷基或(C1-6)烷基；R7和R8独立选择自氢或(C1-6)烷基；R9是氢、(C1-6)氟烷基或(C1-6)烷基；Alk是未取代或取代为羟基的(C1-4)烷基；Y是氧、硫、SO2或键；X是CH2、C=O、S、O或SO2；Z是氢、卤素、(C1-6)烷基、(C1-6)氟烷基、-OH、(C1-6)烷氧基、(C1-6)氟烷氧基、(C1-6)烷硫基、(C1-6)酰基、(C1-4)烷基磺酰基、-OCF3、-NO2、-CN、羧酰胺基，该羧酰胺基可在氮上被一个或两个(C1-4)烷基取代，以及-NH2，其中一个氢原子可被(C1-4)烷基取代，另一个氢原子可被(C1-4)烷基、(C1-6)酰基或(C1-4)烷基磺酰基取代；R1、R2或R3的苯基独立地未取代或取代为从Z中独立选择的一个至三个取代基；R3的单环杂芳基未取代或取代为从Z中独立选择的一个至三个取代基；R3的双环杂芳基未取代或取代为从Z中独立选择的一个至三个取代基；以及其盐、溶剂化合物和晶型形式。还描述了将式(I)的化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相情感障碍的药物，以及式(I)的药物配方。
• Substituted piperazines of azepines, oxazepines and thiazepines
  申请人：He Xiaoqiang John

  公开号：US20060270656A1

  公开（公告）日：2006-11-30

  Described herein are antipyschotic compounds of formula (I) wherein: is an optionally benzo-fused five or six member aromatic ring having zero to three hetero atoms independently selected from N, O, and S; R 1 is hydrogen, (C 1-6 ) fluoroalkyl, (C 3-6 ) cycloalkyl, or (C 1-4 ) alkyl, wherein the (C 1-4 ) alkyl is unsubstituted or substituted with hydroxy, methoxy, ethoxy, OCH 2 CH 2 OH, —CN, imidazolidin-2-one, phenyl, or tetrazole wherein tetrazole is unsubstituted or substituted with (C 1-4 ) alkyl; R 2 is H, halogen, (C 1-6 ) fluoroalkyl, (C 3-6 ) cycloalkyl, OR 6 , SR 6 , NO 2 , CN, COR 6 , C(O)OR 6 , C(OH)R 6 , CONR 7 R 8 , phenyl or (C 1-6 ) alkyl, wherein the (C 1-6 ) alkyl is unsubstituted or substituted with a hydroxy; R 3 is hydrogen, (C 1-6 )fluoroalkyl , (C 3-6 ) cycloalkyl, (C 2-6 ) alkenyl, phenyl, monocyclic heteroaromatic, bicyclic heteroaromatic, or (C 1-4 )alkyl wherein (C 1-4 ) alkyl is unsubstituted or substituted with a phenyl; R 4 and R 5 are independently selected from hydrogen, halogen, (C 1-6 ) alkyl, (C 1-6 ) fluoroalkyl, OR 9 , SR 9 , NO 2 , CN, or COR 9 ; R 6 is hydrogen, (C 1-6 ) fluoroalkyl, or (C 1-6 ) alkyl; R 7 and R 8 are independently hydrogen, or (C 1-6 ) alkyl; R 9 is hydrogen, (C 1-6 ) fluoroalkyl, (C 1-6 ) alkyl; Alk is (C 1-4 ) alkylene unsubstituted or substituted with a hydroxy; Y is oxygen, sulfur, SO 2 , or a bond; X is CH 2 , C═O, S, O, or SO 2 ; Z is hydrogen, halogen, (C 1-6 ) alkyl, (C 1-6 )fluoroalkyl, —OH, (C 1-6 ) alkoxy, (C 1-6 ) fluoroalkoxy, (C 1-6 ) alkylthio, (C 1-6 ) acyl, (C 1-4 )alkylsulfonyl, —OCF 3 , —NO 2 , —CN, carboxamido which may be substituted on the nitrogen by one or two (C 1-4 ) alkyl groups, and —NH 2 in which one of the hydrogens may be replaced by a (C 1-4 ) alkyl group and the other hydrogen may be replaced by either a (C 1-4 ) alkyl group, a (C 1-6 ) acyl group, or a (C 1-4 ) alkylsulfonyl group; the phenyl of R 1 , R 2 or R 3 is independently unsubstituted or substituted with one to three substituents independently selected from Z; the monocyclic heteroaromatic of R 3 is unsubstituted or substituted with one to three substituents independently selected from Z; the bicyclic heteroaromatic of R 3 is unsubstituted or substituted with one to three substituents independently selected from Z; and salts, solvates, and crystal forms thereof. Also described are the use of the compounds of formula (I) as antagonists of the dopamine D 2 receptor and as agents for the treatment of psychosis and bipolar disorders, and pharmaceutical formulations of the compounds of formula (I).

  本文描述了式(I)的抗精神病化合物，其中： - 是一个可选的苯并五元或六元芳香环，其具有0-3个杂原子，独立地选自N，O和S； - R1是氢，(C1-6)氟烷基，(C3-6)环烷基或(C1-4)烷基，其中(C1-4)烷基未取代或取代了羟基，甲氧基，乙氧基，OCH2CH2OH，—CN，咪唑啉-2-酮，苯基或四唑，其中四唑未取代或取代了(C1-4)烷基； - R2是H，卤素，(C1-6)氟烷基，(C3-6)环烷基，OR6，SR6，NO2，CN，COR6，C(O)OR6，C(OH)R6，CONR7R8，苯基或(C1-6)烷基，其中(C1-6)烷基未取代或取代了羟基； - R3是氢，(C1-6)氟烷基，(C3-6)环烷基，(C2-6)烯基，苯基，单环杂芳基，双环杂芳基或(C1-4)烷基，其中(C1-4)烷基未取代或取代了苯基； - R4和R5独立地选自氢，卤素，(C1-6)烷基，(C1-6)氟烷基，OR9，SR9，NO2，CN或COR9； - R6是氢，(C1-6)氟烷基或(C1-6)烷基； - R7和R8独立地是氢或(C1-6)烷基； - R9是氢，(C1-6)氟烷基或(C1-6)烷基； - Alk是(C1-4)烷基，未取代或取代了羟基； - Y是氧，硫，SO2或键； - X是CH2，C═O，S，O或SO2； - Z是氢，卤素，(C1-6)烷基，(C1-6)氟烷基，—OH，(C1-6)烷氧基，(C1-6)氟烷氧基，(C1-6)烷硫基，(C1-6)酰基，(C1-4)烷基磺酰基，—OCF3，—NO2，—CN，羧酰胺，其氮上可能通过一个或两个(C1-4)烷基取代，以及—NH2，在其中一个氢可能被(C1-4)烷基取代，另一个氢可能被(C1-4)烷基，(C1-6)酰基或(C1-4)烷基磺酰基取代； - R1，R2或R3的苯基独立地未取代或取代了1-3个Z取代基； - R3的单环杂芳基未取代或取代了1-3个Z取代基； - R3的双环杂芳基未取代或取代了1-3个Z取代基； - 还描述了该化合物的盐，溶剂化合物和晶体形式。 还描述了将式(I)化合物用作多巴胺D2受体拮抗剂和治疗精神病和双相障碍的药物，以及式(I)化合物的制剂。
• Thienobenzazepine derivatives, processes for their production and pharmaceutical compositions containing them
  申请人：SANDOZ AG

  公开号：EP0001401A1

  公开（公告）日：1979-04-18

  Thienabenzosepines of formula I, wherein R, is hydrogen, halogen. trifluoromethyl or alkyl, alkoxy. alkylthio, alkylsulfinyl or alkylsulfonyl, each of 1 to 4 carbon atoms. R2 is hydrogen, alkyl of 1 to 4 carbon atoms, hydroxyalkyl with a maximum of 4 carbon atoms, which may be acylated by an alkanoyl group of 2 to 18 carbon atoms of alkoxyalkyl with a maximum of 6 carbon atoms, and A is a radical of formula AI or All wherein R3 is hydrogen, halogen, trifluoromethylthio, trifluoromethylsulfinyl, trifluoromethylsulfonyl or alkyl, alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl, each of 1 to 4 carbon atoms. R4 is hydrogen or alkyl of 1 to 4 carbon atoms, with the proviso that one of R3 and R, is hydrogen and the other of R3 and R, is other than hydrogen, and R5 is halogen or alkyl of 1 to 4 carbon atoms, and their preparation. (I) are useful for treating psychotic disturbances, depressions or relaxing muscles.

  式 I 的噻吩并噻吩类化合物、 其中 R，是氢、卤素、三氟甲基或烷基、烷氧基、烷硫基、烷基亚磺酰基或烷基磺酰基，每个均为 1 至 4 个碳原子。 R2 是氢、1 至 4 个碳原子的烷基、最多 4 个碳原子的羟烷基（可被 2 至 18 个碳原子的烷酰基或最多 6 个碳原子的烷氧基烷基酰化），A 是式 AI 或 All 的基团。 其中 R3 是氢、卤素、三氟甲硫基、三氟甲基亚磺酰基、三氟甲基磺酰基或烷基、烷氧基、烷硫基、烷基亚磺酰基或烷基磺酰基，每个基团有 1 至 4 个碳原子。 R4 是氢或 1 至 4 个碳原子的烷基，但 R3 和 R 之一为氢，R3 和 R 之二为非氢，以及 R5 是卤素或 1 至 4 个碳原子的烷基，以及它们的制备方法。 (I) 可用于治疗精神紊乱、抑郁或放松肌肉。
• Hunziker; Fischer; Kipfer, European Journal of Medicinal Chemistry, 1981, vol. 16, # 5, p. 391 - 398
  作者：Hunziker、Fischer、Kipfer、et al.

  DOI：——

  日期：——
• HUNZIKER, F.;FISCHER, R.;KIPFER, P.;SCHMUTZ, J.;BUERKI, H. R.;FICHENBERGE+, EUR. J. MED. CHEM.-CHIM. THER., 1981, 16, N 5, 391-398
  作者：HUNZIKER, F.、FISCHER, R.、KIPFER, P.、SCHMUTZ, J.、BUERKI, H. R.、FICHENBERGE+

  DOI：——

  日期：——