9-chloro-7-(2-chlorophenyl)-6,7-dihydro-6-<(4-methylphenyl)sulfonyl>-5H-pyrimido<5,4-d><2>benzazepine | 76988-74-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 9-chloro-7-(2-chlorophenyl)-6,7-dihydro-6-<(4-methylphenyl)sulfonyl>-5H-pyrimido<5,4-d><2>benzazepine
• 英文别名: 9-Chloro-7-(2-chlorophenyl)-6,7-dihydro-6-[(4-methylphenyl)sulfonyl]-5H-pyrimido[5,4-d][2]benzazepine；9-chloro-7-(2-chlorophenyl)-6-(4-methylphenyl)sulfonyl-5,7-dihydropyrimido[5,4-d][2]benzazepine
• CAS: 76988-74-4
• 化学式: C₂₅H₁₉Cl₂N₃O₂S
• 分子量: 496.417
• InChiKey: HHIFCDLZVSFPEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  71.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-chloro-7-(2-chlorophenyl)-6,7-dihydro-6-<(4-methylphenyl)sulfonyl>-5H-pyrimido<5,4-d><2>benzazepine 生成 9-chloro-7-(2-chlorophenyl)-6,7-dihydro-6-<(4-methylphenyl)sulfonyl>-5H-pyrimido<5,4-d><2>benzazepine 3-oxide
  参考文献：
  名称：

  FRYER, R. I.;GILMAN, N. W.;TRYBULSKI, E. J.;WALSER, A.

  摘要：

  DOI：
• 作为产物：
  描述：

  9-氯-7-(2-氯苯基)-5H-嘧啶并[5,4-d][2]苯并氮杂卓 在 吡啶 、 4-二甲氨基吡啶 、 溶剂黄146 、 锌 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 生成 9-chloro-7-(2-chlorophenyl)-6,7-dihydro-6-<(4-methylphenyl)sulfonyl>-5H-pyrimido<5,4-d><2>benzazepine
  参考文献：
  名称：

  2-Benzazepines. 6. Synthesis and pharmacological properties of the metabolites of 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d][2]benzazepine

  摘要：

  The 2-benzazepine 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (1) has been selected for development as an anxiolytic agent. In support of this program, we have confirmed by chemical synthesis the structures of three in vitro (rat liver homogenate) metabolites of 1 and confirmed the structure of the major in vivo (dog and man) metabolite of 1, compound 2. Two of the metabolites, arising from hydroxylation of the pyrimidobenzazepine ring at the 5-position (2) and N-oxide formation at the 3-position of the pyrimidobenzazepine ring (3), were found to be as active as 1 in a series of pharmacological tests. The third metabolite, formed by hydroxylation of the 7-phenyl group in the 4-position (4), was found to be inactive in the same pharmacological screens.

  DOI：

  10.1021/jm00365a009

文献信息

• Pyrimido-2-benzazepines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04481142A1

  公开（公告）日：1984-11-06

  There is presented compounds of the formula ##STR1## wherein A is selected from the group consisting of ##STR2## R.sub.1 is selected from the group consisting of hydrogen, chlorine, bromine, lower alkyl, the group NR.sub.4 R.sub.5, the group --CH.sub.2 --CO--R.sub.7, the group--NH(CH.sub.2).sub.m NR.sub.8 R.sub.9, hydroxy, lower alkoxy, mercapto and lower alkyl mercapto; R.sub.2 is selected from the group consisting of hydrogen, amino and dilower alkyl amino; R.sub.3 is selected from the group consisting of hydrogen, lower acyloxy and hydroxy; X is selected from the group consisting of hydrogen, halogen, trifluoromethyl, ethyl, .alpha.-hydroxy ethyl and acetyl; Y is hydrogen or halogen; R.sub.4 and R.sub.5 are hydrogen or lower alkyl or together with their co-bonded nitrogen atom form a five to seven membered heterocyclic group; R.sub.7 is selected from the group consisting of hydroxy lower alkoxy and NR.sub.8 R.sub.9 ; R.sub.8 and R.sub.9 are hydrogen or lower alkyl; n is 0 or 1 and m is 1 to 7 with the limitations that (1) at least one of R.sub.1 and R.sub.2 are hydrogen, (2) when R.sub.3 is lower acyloxy or hydroxy, A is the group (a), X is hydrogen, halogen, trifluoromethyl, ethyl or acetyl and R.sub.1 is the group --NH(CH.sub.2).sub.m NR.sub.8 R.sub.9, then R.sub.8 and R.sub.9 are lower alkyl, (3) when A is group (d) and R.sub.1 is the group --NH(CH.sub.2).sub.m NR.sub.8 R.sub.9 then R.sub.8 and R.sub.9 are lower alkyl and (4) when n is 1, R.sub.1 is hydrogen, lower alkyl, lower alkoxy, chlorine, bromine or the group --CH.sub.2 --CO-- R.sub.7 with R.sub.7 as above then A is the group (a) or (b) and the pharmaceutically acceptable salts thereof. The compounds exhibit pharmacological activity as anxiolytics and sedatives. Also presented Are various novel intermediates and processes to produce the above end products.

  该文中介绍了一些化合物，其化学式为##STR1## 其中A从以下组中选择：##STR2## R1从以下组中选择：氢、氯、溴、低碳基、基团NR4R5、基团--CH2--CO--R7、基团--NH(CH2)mNR8R9、羟基、低烷氧基、巯基和低烷基巯基；R2从以下组中选择：氢、氨基和二低烷基氨基；R3从以下组中选择：氢、低酰氧基和羟基；X从以下组中选择：氢、卤素、三氟甲基、乙基、α-羟基乙基和乙酰基；Y为氢或卤素；R4和R5为氢或低烷基，或与它们共键合的氮原子形成五元至七元杂环基团；R7从以下组中选择：羟基低烷氧基和NR8R9；R8和R9为氢或低烷基；n为0或1，m为1至7，限制为：(1)R1和R2中至少有一个为氢；(2)当R3为低酰氧基或羟基时，A为(a)组，X为氢、卤素、三氟甲基、乙基或乙酰基，R1为基团--NH(CH2)mNR8R9，则R8和R9为低烷基；(3)当A为(d)组，R1为基团--NH(CH2)mNR8R9时，则R8和R9为低烷基；(4)当n为1，R1为氢、低烷基、低烷氧基、氯、溴或基团--CH2--CO--R7，其中R7如上所述，则A为(a)或(b)组及其药学上可接受的盐。这些化合物表现出抗焦虑和镇静的药理活性。此外，还介绍了各种新型中间体和生产上述终产品的工艺。
• Pyrimido-2-benzazepines and intermediates in their preparation
  申请人：Hoffmann-La Roche Inc.

  公开号：US04547581A1

  公开（公告）日：1985-10-15

  There is presented compounds of the formula ##STR1## wherein A is selected from the group consisting of ##STR2## R.sub.1 is selected from the group consisting of hydrogen, chlorine, bromine, lower alkyl, the group NR.sub.4 R.sub.5, the group --CH.sub.2 --CO--R.sub.7, the group --NH(CH.sub.2).sub.m NR.sub.8 R.sub.9, hydroxy, lower alkoxy, mercapto and lower alkyl mercapto; R.sub.2 is selected from the group consisting of hydrogen, amino and di-lower alkyl amino; R.sub.3 is selected from the group consisting of hydrogen, lower acyloxy and hydroxy; X is selected from the group consisting of hydrogen, halogen, trifluoromethyl, ethyl, .alpha.-hydroxy ethyl and acetyl; Y is hydrogen or halogen; R.sub.4 and R.sub.5 are hydrogen or lower alkyl or together with their co-bonded nitrogen atom form a five to seven membered heterocyclic group; R.sub.7 is selected from the group consisting of hydroxy lower alkoxy and NR.sub.8 R.sub.9 ; R.sub.8 and R.sub.9 are hydrogen or lower alkyl; n is 0 or 1 and m is 1 to 7 with the limitations that (1) at least one of R.sub.1 and R.sub.2 are hydrogen, (2) when R.sub.3 is lower acyloxy or hydroxy, A is the group (a), X is hydrogen, halogen, trifluoromethyl, ethyl or acetyl and R.sub.1 is the group --NH(CH.sub.2).sub.m NR.sub.8 R.sub.9, then R.sub.8 and R.sub.9 are lower alkyl, (3) when A is group (d) and R.sub.1 is the group --NH(CH.sub.2).sub.m NR.sub.8 R.sub.9 then R.sub.8 and R.sub.9 are lower alkyl and (4) when n is 1, R.sub.1 is hydrogen, lower alkyl, lower alkoxy, chlorine, bromine or the group --CH.sub.2 --CO--R.sub.7 with R.sub.7 as above then A is the group (a) or (b) and the pharmaceutically acceptable salts thereof. The compounds exhibit pharmacological activity as anxiolytics and sedatives. Also presented are various novel intermediates and processes to produce the above end products.

  该文献介绍了公式为##STR1##的化合物，其中A选自以下组中的一种：##STR2## R.sub.1选自以下组中的一种：氢、氯、溴、低烷基、基团NR.sub.4 R.sub.5、基团--CH.sub.2 --CO--R.sub.7、基团--NH(CH.sub.2).sub.m NR.sub.8 R.sub.9、羟基、低烷氧基、巯基和低烷基巯基；R.sub.2选自以下组中的一种：氢、氨基和二低烷基氨基；R.sub.3选自以下组中的一种：氢、低酰氧基和羟基；X选自以下组中的一种：氢、卤素、三氟甲基、乙基、α-羟乙基和乙酰基；Y为氢或卤素；R.sub.4和R.sub.5为氢或低烷基，或与它们的共键氮原子形成五元至七元杂环基团；R.sub.7选自以下组中的一种：羟基低烷氧基和NR.sub.8 R.sub.9；R.sub.8和R.sub.9为氢或低烷基；n为0或1，m为1至7，限制条件为（1）R.sub.1和R.sub.2中至少有一个为氢，（2）当R.sub.3为低酰氧基或羟基时，A为组（a），X为氢、卤素、三氟甲基、乙基或乙酰基，R.sub.1为基团--NH(CH.sub.2).sub.m NR.sub.8 R.sub.9，则R.sub.8和R.sub.9为低烷基，（3）当A为组（d）且R.sub.1为基团--NH(CH.sub.2).sub.m NR.sub.8 R.sub.9时，则R.sub.8和R.sub.9为低烷基，（4）当n为1，R.sub.1为氢、低烷基、低烷氧基、氯、溴或基团--CH.sub.2 --CO--R.sub.7（其中R.sub.7如上所述）时，A为组（a）或（b），以及其药学上可接受的盐。这些化合物表现出抗焦虑和镇静的药理活性。此外，还提供了各种新颖的中间体和生产上述终产品的过程。
• Benzazepin-Derivate, Verfahren und Zwischenprodukte zu deren Herstellung, deren Verwendung sowie diese enthaltende Arzneimittel
  申请人：F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft

  公开号：EP0014470A2

  公开（公告）日：1980-08-20

  Pyrimido-2-benzazepine der allgemeinen Formel worin A eine der Gruppen R1 Wasserstoff, Chlor, Brom, niederes Alkyl, die Gruppe NR4R5, die Gruppe -CH2-CO-R7, die Gruppe -NH(CH2)mNR8R9, Hydroxy, niederes Alkoxy, Mercapto oder niederes Alkylmercapto, R2 Wasserstoff, Amino oder Di-(nieder)-alkylamino, R Wasserstoff, niederes Acyloxy oder Hydroxy, X Wasserstoff, Halogen, Trifluormethyl, Aethyl, a-Hydroxyäthyl oder Acetyl, Y Wasserstoff oder Halogen, R4 und R5 je Wasserstoff oder niederes Alkyl oder, zusammen mit dem Stickstoffatom, einen 5- bis7-gliedrigen Heterocyclus, welcher ein Sauerstoff-oder Schwefelatom oder die Gruppe N-Niederalkyl enthalten kann, R7 Wasserstoff, niederes Alkoxy oder NR8R9, R6 und R9 je Wasserstoff oder niederes Alkyl, n 0 oder 1 und m 1 bis 7 bedeuten, mit der Massgabe, dass (i) mindestens eines von R1 und R2 Wasserstoff ist; (ii) wenn R3 niederes Acyloxy oder Hydroxy bedeutet, A Gruppe (a), X Wasserstoff, Halogen, Trifluormethyl, Aethyl oder Acetyl und, wenn R1 die Gruppe -NH(CH2)mNR8R9 bedeutet, R' und R9 je niederes Alkyl bedeuten; (iii) wenn A Gruppe (d) und R1 die Gruppe -NH(CH2)mNR8R9 bedeuten, R' und R9 je niederes Alkyl bedeuten; und (iv) wenn n 1 bedeutet, R1 Wasserstoff, niederes Alkyl, niederes Alkoxy, Chlor, Brom oder die Gruppe -CH2-CO-R7 (worin R7 obige Bedeutung besitzt) und A Gruppe (a) oder (b) bedeuten; und pharmazeutisch akzeptable Säureadditionssalze davon sind neu und pharmakologisch verwertbar als Anxiolytika und Sedativa. Diese Verbindungen und Salze können nach verschiedenen Methoden ausgehend von teilweise neuen Zwischenprodukten hergestellt werden.

  通式如下的嘧啶-2-苯并氮杂卓 其中 A 为以下基团之一 R1 是氢、氯、溴、低级烷基、基团 NR4R5、基团 -CH2-CO-R7、基团 -NH(CH2)mNR8R9、羟基、低级烷氧基、巯基或低级烷基巯基，R2 是氢、氨基或二(低级)烷基氨基，R 是氢、低级酰氧基或羟基，X 是氢、卤素、三氟甲基、乙基、a-羟乙基或乙酰基，Y 是氢或卤素、R4 和 R5 分别是氢或低级烷基，或与氮原子一起是 5 至 7 元杂环，该杂环可含有氧原子或硫原子或 N-低级烷基，R7 是氢、低级烷氧基或 NR8R9，R6 和 R9 分别是氢或低级烷基，n 是 0 或 1，m 是 1 至 7，但有以下限制条件： 1. (i) R1 和 R2 中至少有一个是氢 (ii) 当 R3 是低级酰氧基或羟基时，A 是(a)组，X 是氢、卤素、三氟甲基、乙基或乙酰基，当 R1 是基团 -NH(CH2)mNR8R9 时，R'和 R9 各自是低级烷基； (iii) 当 A 为基团(d)且 R1 为基团-NH(CH2)mNR8R9 时，R'和 R9 各为低级烷基；以及 (iv) 当 n 为 1 时，R1 为氢、低级烷基、低级烷氧基、氯、溴或基团 -CH2-CO-R7（其中 R7 如上定义），且 A 为基团 (a) 或 (b)； 及其药学上可接受的酸加成盐是新颖的、药理上可用作抗焦虑药和镇静剂的化合物。这些化合物和盐可以通过各种方法从部分新的中间体开始制备。
• TRYBULSKI, E. J.;FRYER, R. I.;REEDER, E.;WALSER, A.;BLOUNT, J., J. MED. CHEM., 1983, 26, N 11, 1596-1601
  作者：TRYBULSKI, E. J.、FRYER, R. I.、REEDER, E.、WALSER, A.、BLOUNT, J.

  DOI：——

  日期：——
• FRYER, R. I.;GILMAN, N. W.;TRYBULSKI, E. J.;WALSER, A.
  作者：FRYER, R. I.、GILMAN, N. W.、TRYBULSKI, E. J.、WALSER, A.

  DOI：——

  日期：——