[benzotriazol-1-yl(2-benzoyl-4-chloro-phenylcarbamoyl)-methyl]-carbamic acid benzyl ester | 676127-91-6

• 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: [benzotriazol-1-yl(2-benzoyl-4-chloro-phenylcarbamoyl)-methyl]-carbamic acid benzyl ester
• 英文别名: benzyl N-[1-(benzotriazol-1-yl)-2-(2-benzoyl-4-chloroanilino)-2-oxoethyl]carbamate
• CAS: 676127-91-6
• 化学式: C₂₉H₂₂ClN₅O₄
• 分子量: 539.978
• InChiKey: KLVDMKBRUZPDEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [benzotriazol-1-yl(2-benzoyl-4-chloro-phenylcarbamoyl)-methyl]-carbamic acid benzyl ester 在 劳森试剂 、 ammonium acetate 、 氨 、 一水合肼 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 46.0h， 生成
  参考文献：
  名称：

  Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

  摘要：

  The bromo and extra C-terminal domain (BET) family of bromodomains are involved in binding epigenetic marks on histone proteins, more specifically acetylated lysine residues. This paper describes the discovery and structure activity relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a potent, selective compound I-BET762 that is now under evaluation in a phase I/II clinical trial for nuclear protein in testis (NUT) midline carcinoma and other cancers.

  DOI：

  10.1021/jm401088k
• 作为产物：
  描述：

  2-(1H-苯并[d][1,2,3]噻唑-1-基)-2-(((苄氧基)羰基)氨基)乙酸 在 N-甲基吗啉 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 [benzotriazol-1-yl(2-benzoyl-4-chloro-phenylcarbamoyl)-methyl]-carbamic acid benzyl ester
  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

• [EN] BENZODIAZEPINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] DERIVES DE BENZODIAZEPINE ET COMPOSITIONS PHARMACEUTIQUES LES RENFERMANT
  申请人：ARROW THERAPEUTICS LTD

  公开号：WO2004026843A1

  公开（公告）日：2004-04-01

  Benzodiazepine derivative of formula (I), and pharmaceutically acceptable salts thereof, are found to be active against RSV. Formula (I) Wherein: - R1 represents C1-6 alkyl, aryl or heteroaryl; - R2 represents hydrogen or C1-6 alkyl; - 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, -CO2RI, -CONRIRII, -NH-CO-RI, -S(O)RI, -S(O)2RI, -NH-S(O)2RI, -S(O)NRIRII or -S(O)2NRIRII wherein each RI and RII is the same or different and represents hydrogen or C1-6 alkyl; - n is from 0 to 3; R4 represents hydrogen or C1-6 alkyl; - R6 represents C1-6 alkyl, aryl, heteroaryl, carbocyclyl, heterocyclyl, aryl-(C1-6 alkyl)-, heteroaryl-(C1-6 alkyl)-, carbocyclyl-(C1-6 alkyl)-, heterocyclyl-(C1-6 alkyl)-, aryl-C(O)-C(O)-, heteroaryl-C(O)-C(O)-, carbocyclyl-C(O)-C(O)-, heterocyclyl-C(O)-C(O)- or, -XR6; - X represents -CO-, -S(O)- or -S(0)2-; and - R6 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-(C 1-6hydroxyalkyl)-, heteroaryl-(C1-6 hydroxyalkyl)-, carbocyclyl-(C1-6 hydroxyalkyl)-, heterocyclyl-(C 1-6 hydroxyalkyl)-, aryl-(C 1-6alkyl)-O-, heteroaryl-(C 1-6alkyl)-O-, carbocyclyl-(C1-6 alkyl)-O-, heterocyclyl-(C1-6 alkyl)-O- or -NRIRII wherein each RI and RII 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)-.

  苯二氮卓衍生物的化学式（I）及其药学上可接受的盐被发现对RSV具有活性。化学式（I）其中：- R1代表C1-6烷基，芳基或杂芳基；- R2代表氢或C1-6烷基；- 每个R3相同或不同，代表卤素，羟基，C1-6烷基，C1-6烷氧基，C1-6烷硫基，C1-6卤代烷基，C1-6卤代烷氧基，氨基，单（C1-6烷基）氨基，二（C1-6烷基）氨基，硝基，氰基，-CO2RI，-CONRIRII，-NH-CO-RI，-S(O)RI，-S(O)2RI，-NH-S(O)2RI，-S(O)NRIRII或-S(O)2NRIRII其中每个RI和R...
• Benzodiazepine derivatives and pharmaceutical compositions containing them
  申请人：Carter Malcolm

  公开号：US20060040923A1

  公开（公告）日：2006-02-23

  Benzodiazepine derivative of formula (I), and pharmaceutically acceptable salts thereof, are found to be active against RSV. Formula (I) Wherein: —R 1 represents C 1-6 alkyl, aryl or heteroaryl; —R 2 represents hydrogen or C 1-6 alkyl; —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; R 4 represents hydrogen or C 1-6 alkyl; —R 6 represents C 1-6 alkyl, 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(O)—C(O)—, heteroaryl-C(O)—C(O)—, carbocyclyl-C(O)—C(O)—, heterocyclyl-C(O)—C(O)— or, —XR 6 ; —X represents —CO—, —S(O)— or —S(O) 2 —; and —R 6 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 hydroxyalkyl)-, heteroaryl-(C 1-6 hydroxyalkyl)-, carbocyclyl-(C 1-6 hydroxyalkyl)-, heterocyclyl-(C 1-6 hydroxyalkyl)-, 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)-.

  公式（I）的苯二氮平衍生物及其药学上可接受的盐被发现对RSV具有活性。公式（I）中：-R1表示C1-6烷基，芳基或杂环芳基；-R2表示氢或C1-6烷基；-每个R3相同或不同，表示卤素，羟基，C1-6烷基，C1-6烷氧基，C1-6烷硫基，C1-6卤代烷基，C1-6卤代烷氧基，氨基，单（C1-6烷基）氨基，双（C1-6烷基）氨基，硝基，氰基，-CO2R'，-CONR'R"，-NH-CO-R'，-S（O）R'，-S（O）2R'，-NH-S（O）2R'，-S（O）NR'R"或-S（O）2NR'R"，其中每个R'和R"相同或不同，表示氢或C1-6烷基；-n为0-3；-R4表示氢或C1-6烷基；-R6表示C1-6烷基，芳基，杂环芳基，碳环基，杂环基，芳基（C1-6烷基），杂环芳基（C1-6烷基），碳环基（C1-6烷基），杂环基（C1-6烷基），芳基-C（O）-C（O）-，杂环芳基-C（O）-C（O）-，碳环基-C（O）-C（O）-，杂环基-C（O）-C（O）-或-XR6；-X表示-CO-，-S（O）-或-S（O）2-；-R6表示C1-6烷基，羟基，C1-6烷氧基，C1-6烷硫基，芳基，杂环芳基，碳环基，杂环基，芳基（C1-6烷氧基），杂环芳基（C1-6烷氧基），碳环基（C1-6烷氧基），杂环基（C1-6烷氧基），芳基（C1-6羟基烷基），杂环芳基（C1-6羟基烷基），碳环基（C1-6羟基烷基），杂环基（C1-6羟基烷基），芳基（C1-6烷基）-O-，杂环芳基（C1-6烷基）-O-，碳环基（C1-6烷基）-O-，杂环基（C1-6烷基）-O-或-NR'R"，其中每个R'和R"相同或不同，表示氢，C1-6烷基，碳环基，杂环基，芳基，杂环芳基，芳基（C1-6烷基），杂环芳基（C1-6烷基），碳环基（C1-6烷基）或杂环基（C1-6烷基）。
• Benzodiazepine Derivatives and Pharmaceutical Compositions Containing Them
  申请人：Carter Malcolm

  公开号：US20100015063A1

  公开（公告）日：2010-01-21

  Benzodiazepine derivative of formula (I), and pharmaceutically acceptable salts thereof, are found to be active against RSV Formula (I) Wherein: —R 1 represents C 1-6 alkyl, aryl or heteroaryl; —R 2 represents hydrogen or C 1-6 alkyl; -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; R 4 represents hydrogen or C 1-6 alkyl; —R 6 represents C 1-6 alkyl, 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(O)—C(O)—, heteroaryl-C(O)—C(O)—, carbocyclyl-C(O)—C(O)—, heterocyclyl-C(O)—C(O)— or, —XR 6 ; —X represents —CO—, —S(O)— or —S(0) 2 —; and —R 6 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 hydroxyalkyl)-, heteroaryl-(C 1-6 hydroxyalkyl)-, carbocyclyl-(C 1-6 hydroxyalkyl)-, heterocyclyl-(C 1-6 hydroxyalkyl)-, 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)-.

  公式（I）的苯二氮平衍生物及其药学上可接受的盐被发现对RSV具有活性，其中： - —R1代表C1-6烷基，芳基或杂环芳基； - —R2代表氢或C1-6烷基； - 每个R3相同或不同，代表卤素，羟基，C1-6烷基，C1-6烷氧基，C1-6烷基硫基，C1-6卤代烷基，C1-6卤代烷氧基，氨基，单（C1-6烷基）氨基，二（C1-6烷基）氨基，硝基，氰基，—CO2R′，CONR′R″，—NH—CO—R′，—S（O）R′，—S（O）2R′，—NH—S（O）2R′，—S（O）NR′R″或—S（O）2NR′R″，其中每个R′和R″相同或不同，代表氢或C1-6烷基； - n为0至3； - R4代表氢或C1-6烷基； - —R6代表C1-6烷基，芳基，杂环芳基，碳环烷基，杂环烷基，芳基-(C1-6烷基)-，杂环芳基-(C1-6烷基)-，碳环烷基-(C1-6烷基)-，杂环烷基-(C1-6烷基)-，芳基-C（O）-C（O）-，杂环芳基-C（O）-C（O）-，碳环烷基-C（O）-C（O）-，杂环烷基-C（O）-C（O）-或—XR6; - —X代表-CO-，-S（O）-或-S（0）2-； - —R6代表C1-6烷基，羟基，C1-6烷氧基，C1-6烷基硫基，芳基，杂环芳基，碳环烷基，杂环烷基，芳基-(C1-6烷基)-，杂环芳基-(C1-6烷基)-，碳环烷基-(C1-6烷基)-，杂环烷基-(C1-6烷基)-，芳基-(C1-6羟基烷基)-，杂环芳基-(C1-6羟基烷基)-，碳环烷基-(C1-6羟基烷基)-，杂环烷基-(C1-6羟基烷基)-，芳基-(C1-6烷基)-O-，杂环芳基-(C1-6烷基)-O-，碳环烷基-(C1-6烷基)-O-，杂环烷基-(C1-6烷基)-O-或—NR′R″，其中每个R′和R″相同或不同，代表氢，C1-6烷基，碳环烷基，杂环烷基，芳基，杂环芳基，芳基-(C1-6烷基)-，杂环芳基-(C1-6烷基)-，碳环烷基-(C1-6烷基)-或杂环烷基-(C1-6烷基)-。
• BENZODIAZEPINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
  申请人：Arrow Therapeutics Limited

  公开号：EP1539716A1

  公开（公告）日：2005-06-15
• US7582624B2
  申请人：——

  公开号：US7582624B2

  公开（公告）日：2009-09-01