4-methoxy N-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)benzamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-methoxy N-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)benzamide
• 英文别名: 4-methoxy-N-(2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl)benzamide
• 化学式: C₂₃H₁₉N₃O₃
• 分子量: 385.422
• InChiKey: AMZMREZQJXXMIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  79.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  benzyl N-[[(2-benzoylphenyl)carbamoyl](1H-1,2,3-benzotriazol-1-yl)methyl]carbamate 在 氨 、 氢溴酸 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.5h， 生成 4-methoxy N-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)benzamide
  参考文献：
  名称：

  1,4-Benzodiazepines as Inhibitors of Respiratory Syncytial Virus

  摘要：

  Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC50's less than 50 mu M. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.

  DOI：

  10.1021/jm051185t

文献信息

• PHARMACEUTICAL COMPOSITION COMPRISING A BENZODIAZEPINE DERIVATIVE AND AN INHIBITOR OF THE RSV FUSION PROTEIN
  申请人：Arrow Therapeutics Limited

  公开号：EP1727550B1

  公开（公告）日：2009-07-29
• Process for Preparing Benzodiazepines
  申请人：Dowdell Verity

  公开号：US20070293482A1

  公开（公告）日：2007-12-20

  A process for producing a compound which is a benzodiazepine derivative of formula: (I) wherein: represents or R 1 represents C 1-6 alkyl, aryl or heteroaryl; each R 3 is the same or different and represents halogen, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 haloalkyl, C 1-6 haloalkoxy, amino, mono(C 1-6 alkyl)amino, di(C 1-6 alkyl)amino, nitro, cyano, —CO 2 R′, —CONR′R″, —NH—CO—R′, —S(O)R′, —S(O) 2 R′, —NH—S(O) 2 R′, —S(O)NR′R″ or —S(O) 2 NR′R″, wherein each R′ and R″ is the same or different and represents hydrogen or C 1-6 alkyl; n is from 0 to 3; X represents —NH—, —N(C 1 -C 6 alkyl)-, —CO—, —CO—NR′—, —S(O)— or —S(O) 2 —, wherein R′ is hydrogen or a C 1 -C 6 alkyl group; and R 4 represents hydrogen; or —CO—R 4 ′ or —CO—NH—R 4 ′ , wherein R 4 ′ is a C 1 -C 6 alkyl, C 1 -C 6 hydroxyalkyl, aryl, heteroaryl, carbocyclyl or heterocyclyl group, which group is substituted by a C 1 -C 6 hydroxyalkyl, aryl, heteroaryl, carbocyclyl or heterocyclyl group or a —(C 1 -C 4 alkyl)-X 1 —(C 1 -C 4 alkyl)-X 2 —(C 1 -C 4 alkyl) group, wherein X 1 represents —O—, —S— or —NR′—, wherein R′ represents H or a C 1 -C 4 alkyl group and X 2 represents —CO—, —SO— or —SO 2 —; or R 4 ′ represents -A 1 -Y-A 2 , wherein: A 1 is an aryl, heteroaryl, carbocyclyl or heterocyclyl group; Y represents a direct bond or a C 1 -C 4 alkylene, —SO 2 —, —CO—, —O—, —S or —NR′—, wherein R′ is a C 1 -C 6 alkyl group; and A 2 is an aryl, heteroaryl, carbocyclyl or heterocyclyl group; or R 4 is a group selected from aryl-C(O)—C(O)—, heteroaryl-C(O)—C(O)—, carbocyclyl-C(O)—C(O)—, heterocyclyl-C(O)—C(O)— and -ZR 5 , wherein: Z represents —CO—, —S(O)— or —S(O) 2 ′; and R 5 represents C 1-6 alkyl, hydroxy, C 1-6 alkoxy, C 1-6 alkylthio, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C 1-6 alkyl)-, heteroaryl-(C 1-6 alkyl)-, carbocyclyl-(C 1-6 alkyl)-, heterocyclyl-(C 1-6 alkyl)-, aryl-(C 1-6 alkyl)-O—, heteroaryl-(C 1-6 alkyl)-O—, carbocyclyl-(C 1-6 alkyl)-O—, heterocyclyl-(C 1-6 alkyl)-O— or —NR′R″ wherein each R′ and R″ is the same or different and represents hydrogen, C 1-6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aryl-(C 1-6 alkyl)-, heteroaryl-(C 1-6 alkyl)-, carbocyclyl-(C 1-6 alkyl)- or heterocyclyl-(C 1-6 alkyl)-; or a pharmaceutically acceptable salt thereof; which process comprises: (a) subjecting a racemic benzodiazepine derivative of formula: (IIa): wherein R 1 , R 3 , R 4 , n and X are as defined above, and R 2 represents an amino protecting group, to crystallisation induced dynamic resolution to yield a benzodiazepine derivative of formula (II): wherein, R 1 , R 2 , R 3 , R 4 , n and X are as defined above; and (b) deprotecting the benzodiazepine derivative of formula (II) as defined above to yield a benzodiazepine derivative of formula (I) or a pharmaceutically acceptable form thereof as defined above.
• [EN] PROCESS FOR PREPARING BENZODIAZEPINES<br/>[FR] PROCEDE DE PREPARATION DE BENZODIAZEPINES
  申请人：ARROW THERAPEUTICS LTD

  公开号：WO2005090319A1

  公开（公告）日：2005-09-29

  A process for producing a compound which is a benzodiazepine derivative of formula: (I) wherein: represents or R1 represents C1-6 alkyl, aryl or heteroaryl; each R3 is the same or different and represents halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 haloalkyl, C1-6 haloalkoxy, amino, mono(C1-6 alkyl)amino, di(C1-6 alkyl)amino, nitro, cyano, -CO2R/, -CONR/R//, -NH-CO-R/, -S(O)R/, -S(O)2R/, -NH-S(O)2R/, -S(O)NR/R// or -S(O)2NR/R//, wherein each R/ and R// is the same or different and represents hydrogen or C1-6 alkyl; n is from 0 to 3; X represents -NH-, -N(C1-C6 alkyl)-, -CO-, -CO-NR/-, -S(O)- or -S(O)2-, wherein R/ is hydrogen or a C1-C6 alkyl group; and R4 represents hydrogen; or -CO-R4' or -CO-NH-R4', wherein R4' is a C1-C6 alkyl, C1-C6 hydroxyalkyl, aryl, heteroaryl, carbocyclyl or heterocyclyl group, which group is substituted by a C1-C6 hydroxyalkyl, aryl, heteroaryl, carbocyclyl or heterocyclyl group or a -(C1-C4 alkyl)-X1-(C1-C4 alkyl)-X2-(C1-C4 alkyl) group, wherein X1 represents -O-, -S- or -NR/-, wherein R/ represents H or a C1-C4 alkyl group and X2 represents -CO-, -SO- or -SO2-; or R4' represents -A1-Y-A2, wherein: Al is an aryl, heteroaryl, carbocyclyl or heterocyclyl group; Y represents a direct bond or a C1-C4 alkylene, -SO2-, -CO-, -O-, -S or -NR/-, wherein R/ is a C1-C6 alkyl group; and A2 is an aryl, heteroaryl, carbocyclyl or heterocyclyl group; or R4 is a group selected from aryl-C(O)-C(O)-, heteroaryl-C(O)-C(O)-, carbocyclyl-C(O)-C(O)-, heterocyclyl-C(O)-C(O)- and -ZR5, wherein: Z represents -CO-, -S(O)- or -S(O)2-; and R5 represents C1-6 alkyl, hydroxy, C1-6 alkoxy, C1-6 alkylthio, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, carbocyclyl-(C1-6 alkyl)-, heterocyclyl-(C1-6 alkyl)-, aryl-(C1-6 alkyl)-O-, heteroaryl-(C1-6 alkyl)-O-, carbocyclyl-(C1-6 alkyl)-O-, heterocyclyl-(C1-6 alkyl)-O- or -NR/R// wherein each R/ and R// is the same or different and represents hydrogen, C1-6 alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, aryl-(C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, carbocyclyl-(C1-6 alkyl)- or heterocyclyl-(C1-6 alkyl)-; or a pharmaceutically acceptable salt thereof; which process comprises: (a) subjecting a racemic benzodiazepine derivative of formula: (IIa): wherein R1, R3, R4, n and X are as defined above, and R2 represents an amino protecting group, to crystallisation induced dynamic resolution to yield a benzodiazepine derivative of formula (II): wherein, R1, R2, R3, R4, n and X are as defined above; and (b) deprotecting the benzodiazepine derivative of formula (II) as defined above to yield a benzodiazepine derivative of formula (I) or a pharmaceutically acceptable form thereof as defined above.
• 1,4-Benzodiazepines as Inhibitors of Respiratory Syncytial Virus
  作者：Malcolm C. Carter、Dagmar G. Alber、Robert C. Baxter、Sian K. Bithell、Jo Budworth、Ann Chubb、G. Stuart Cockerill、Verity C. L. Dowdell、Elisa A. Henderson、Sally J. Keegan、Richard D. Kelsey、Michael J. Lockyer、Jeremy N. Stables、Lara J. Wilson、Kenneth L. Powell

  DOI：10.1021/jm051185t

  日期：2006.4.1

  Respiratory syncytial virus (RSV) is the cause of one-fifth of all lower respiratory tract infections worldwide and is increasingly being recognized as a serious threat to patient groups with poorly functioning immune systems. Our approach to finding a novel inhibitor of this virus was to screen a 20 000-member diverse library in a whole cell XTT assay. Parallel assays were carried out in the absence of virus in order to quantify any associated cell toxicity. This identified 100 compounds with IC50's less than 50 mu M. A-33903 (18), a 1,4-benzodiazepine analogue, was chosen as the starting point for lead optimization. This molecule was moderately active and demonstrated good pharmacokinetic properties. The most potent compounds identified from this work were A-58568 (47), A-58569 (44), and A-62066 (46), where modifications to the aromatic substitution enhanced potency, and A-58175 (42), where the amide linker was modified.