(R)-3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one | 796038-21-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: (R)-3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one
• 英文别名: (R)-3-amino-5-phenyl-1,3-dihydro-2H-benzo[e][1,4]diazepin-2-one；(R)-3-Amino-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one；(3R)-3-amino-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 796038-21-6
• 化学式: C₁₅H₁₃N₃O
• 分子量: 251.288
• InChiKey: GLUWBSPUUGLXCW-CQSZACIVSA-N

物化性质

• 沸点：
  456.7±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以0.9 kg的产率得到3-氨基-5-苯基-1,3-二氢-2H-1,4-苯并二氮杂革-2-酮
  参考文献：
  名称：

  [EN] PROCESSES FOR THE PREPARATION OF BENZODIAZEPINE DERIVATIVES
  [FR] PROCÉDÉS POUR LA PRÉPARATION DE DÉRIVÉS DE BENZODIAZÉPINE

  摘要：

  本发明涉及用于制备生物活性分子的过程和中间体，特别是用于合成呼吸道合胞病毒(RSV)抑制剂的过程。本发明还涉及用于制备式(I)化合物的过程和中间体。特别是，本发明还涉及用于制备化合物(I-a)的过程和中间体。

  公开号：

  WO2018152413A1
• 作为产物：
  描述：

  (R,S)-N-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-3-phenyl-2-(3-phenylthioureido)propionamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以55%的产率得到(R)-3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one
  参考文献：
  名称：

  1,4-Benzodiazepines as Inhibitors of Respiratory Syncytial Virus. The Identification of a Clinical Candidate

  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 representing a serious threat to patient groups with poorly functioning or immature immune systems. Racemic 1,4-benzodiazepines show potent anti-RSV activity in vitro. Anti-RSV evaluation of 3-position R- and S-benzodiazepine enantiomers and subsequent optimization of this series resulted in selection of a clinical candidate. Antiviral activity was found to reside mainly in the S-enantiomer, and the R-enantiomers were consistently less active against RSV. Analogues of 1,4-(S)-benzodiazepine were synthesized as part of the lead optimization program at Arrow and tested in the XTT assay. From this exercise, (S)-1-(2-fluorophenyl)-3-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]-diazepin-3-yl)-urea, 17b (RSV-604) was identified as a clinical candidate, exhibiting potent anti-RSV activity in the XTT assay, which was confirmed in secondary assays. Compound 17b also possessed a good pharmacokinetic profile and has now progressed into the clinic.

  DOI：

  10.1021/jm060747l

文献信息

• Improved Synthesis of Capuramycin and Its Analogues
  作者：Yong Wang、Shajila Siricilla、Bilal A. Aleiwi、Michio Kurosu

  DOI：10.1002/chem.201302389

  日期：2013.10.4

  Capuramycin and its congeners are considered to be important lead molecules for the development of a new drug for multidrug‐resistant (MDR) Mycobacterium tuberculosis infections. Extensive structure–activity relationship studies of capuramycin to improve the efficacy have been limited because of difficulties in selectively chemically modifying the desired position(s) of the natural product with biologically

  卡普拉霉素及其同系物被认为是开发治疗多重耐药 (MDR)结核分枝杆菌感染新药的重要先导分子。由于难以用生物学上感兴趣的官能团选择性地化学修饰天然产物的所需位置，因此为提高功效而对辣椒霉素进行的广泛的结构-活性关系研究受到了限制。我们通过使用源自手性（氯-4-甲氧基苯基）（氯苯基）甲醇的新保护基团，针对尿苷脲基氮和伯醇，开发了卡普拉霉素及其类似物的高效合成方法。手性非外消旋(2,6-二氯-4-甲氧基苯基)(2,4-二氯苯基)甲醇衍生物是解析外消旋-3-氨基-1,3-二氢-5-苯基-2 H ‐1的有用试剂， 4-苯二氮卓-2-酮，其( S )构型异构体在提高卡普拉霉素的杀分枝杆菌活性方面发挥着重要作用。
• [EN] 4- BROMO - 5 - (2- CHLORO - BENZOYLAMINO) - 1H - PYRAZOLE - 3 - CARBOXYLIC ACID AMIDE DERIVATIVES AND RELATED COMPOUNDS AS BRADYKININ B1 RECEPTOR ANTAGONISTS FOR THE TREATMENT OF INFLAMMATORY DISEASES<br/>[FR] DERIVES AMIDES DE L'ACIDE CARBOXYLIQUE DE 4- BROMO - 5 - (2- CHLORO - BENZOYLAMINO) - 1H - PYRAZOLE 3 ET COMPOSES ASSOCIES EN TANT QU'ANTAGONISTES DE RECEPTEUR DE B1 DE LA BRADYKININE POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES
  申请人：ELAN PHARM INC

  公开号：WO2004098589A1

  公开（公告）日：2004-11-18

  Disclosed are compounds of formula I and II that are bradykinin B1 receptor antagonists and are useful for treating diseases, or relieving adverse symptoms associated with disease conditions, in mammals mediated by bradykinin B1 receptor. Certain of the compounds exhibit increased potency and are also expected to exhibit increased duration of action.

  公开的是化合物I和II的结构式，它们是激肽酶B1受体拮抗剂，适用于治疗哺乳动物中由激肽酶B1受体介导的疾病，或缓解与疾病状况相关的不良症状。其中某些化合物表现出增强的效力，并且预计还将表现出延长作用的特性。
• [EN] PROCESSES FOR THE RESOLUTION OF BENZODIAZEPIN-2-ONE AND BENZOAZEPIN-2-ONE DERIVATIVES<br/>[FR] PROCÉDÉ POUR LA RÉSOLUTION DE DÉRIVÉS BENZODIAZÉPIN-2-ONE ET BENZOAZÉPIN-2-ONE
  申请人：ENANTA PHARM INC

  公开号：WO2019094903A1

  公开（公告）日：2019-05-16

  The present invention relates to processes and intermediates useful in the preparation of biologically active molecules, especially in the synthesis of Respiratory Syncytial Virus (RSV) inhibitors. The present invention also relates to processes and intermediates for the preparation of compounds of Formula (1-0) and Formula (I):

  本发明涉及用于制备生物活性分子的过程和中间体，特别是合成呼吸道合胞病毒（RSV）抑制剂的过程。本发明还涉及用于制备Formula（1-0）和Formula（I）化合物的过程和中间体。
• BISFLUOROALKYL-1,4-BENZODIAZEPINONE COMPOUNDS
  申请人：GAVAI ASHVINIKUMAR V.

  公开号：US20120245151A1

  公开（公告）日：2012-09-27

  Disclosed are compounds of Formula (I) or prodrugs thereof; wherein: R 1 is —CH 2 CF 3 or —CH 2 CH 2 CF 3 ; R 2 is —CH 2 CF 3 , —CH 2 CH 2 CF 3 , or —CH 2 CH 2 CH 2 CF 3 ; R 3 is H or —CH 3 ; each R a is independently F, Cl, —CN, —OCH 3 , and/or —NHCH 2 CH 2 OCH 3 ; and z is zero, 1, or 2. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  揭示了Formula (I)的化合物或其前药；其中：R1为—CH2CF3或—CH2CH2CF3；R2为—CH2CF3，—CH2CH2CF3，或—CH2CH2CH2CF3；R3为H或—CH3；每个Rai独立地为F，Cl，—CN，—O ，和/或—NHCH2CH2O ；z为零，1或2。还揭示了使用这些化合物来抑制Notch受体的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或障碍方面是有用的，比如癌症。
• [EN] PRODRUGS OF 1,4-BENZODIAZEPINONE COMPOUNDS<br/>[FR] PROMÉDICAMENTS DE COMPOSÉS 1,4-BENZODIAZÉPINONES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014047391A1

  公开（公告）日：2014-03-27

  Disclosed are compounds of Formula (I) and salts thereof, wherein: a) R1 is H or CH3, and R2 is Ry; or b) R1 is Rx and R2 is H; wherein Rx and Ry are disclosed herein. Also disclosed are methods of using such compounds to inhibit the Notch receptor, and pharmaceutical compositions comprising such compounds. These compounds are prodrugs of compounds that are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as cancer.

  揭示了Formula (I)的化合物及其盐，其中：a) R1为H或CH3，R2为Ry；或b) R1为Rx，R2为H；其中Rx和Ry在此处披露。还披露了使用这些化合物抑制Notch受体的方法，以及包含这些化合物的药物组合物。这些化合物是用于治疗、预防或减缓多种治疗领域的疾病或障碍的化合物的前药，如癌症。