(R)-7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,4-benzodiazepine-2-one | 50691-97-9

• 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)-7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,4-benzodiazepine-2-one
• 英文别名: (R)-7-chloro-3-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one；7-chloro-3-methyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one；2H-1,4-Benzodiazepin-2-one, 1,3-dihydro-7-chloro-3-methyl-5-phenyl-, (R)-；(3R)-7-chloro-3-methyl-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 50691-97-9
• 化学式: C₁₆H₁₃ClN₂O
• 分子量: 284.745
• InChiKey: SATGIBNNISQKBG-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,4-benzodiazepine-2-one 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 (R)-7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,4-benzodiazepine
  参考文献：
  名称：

  Gratton; Decorte; Moimas, Farmaco, Edizione Scientifica, 1985, vol. 40, # 3, p. 209 - 217

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氨基-5-氯二苯甲酮 在 盐酸 、 sodium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 水 为溶剂， 反应 18.0h， 生成 (R)-7-chloro-1,3-dihydro-3-methyl-5-phenyl-2H-1,4-benzodiazepine-2-one
  参考文献：
  名称：

  Discrimination between Enantiomers of Structurally Related Molecules:  Separation of Benzodiazepines by Molecularly Imprinted Polymers

  摘要：

  Molecular imprinting has been used to create synthetic receptor sites for a series of chiral benzodiazepines. A detailed HPLC analysis of binding properties using molecularly imprinted polymers (MIPs) as the stationary phase showed that binding, as measured by chromatographic retention, shows significant dependence on the chiral match or mismatch. In addition, the shape and spatial orientation of functionality of the imprinted binding site is also critical for recognition. Imprinted polymers, therefore, are not only able to discriminate between enantiomers of the imprinted molecule, they also demonstrate an ability to discriminate between a wide range of enantiomers of structurally related molecules that have not been imprinted. The ability of MIPs to discriminate between enantiomers of molecules in favor of the imprinted absolute configuration, even as the structural homology between the enantiomers and the original template decreases, indicates that the synthetic benzodiazepine receptors may serve as crude mimics of the natural receptor.

  DOI：

  10.1021/ja9926313

文献信息

• [EN] 1,3-DIHYDRO-1,4-BENZODIAZEPINE-2-THIONES FOR THE TREATMENT OF CNS RELATED DISEASES<br/>[FR] 1,3-DIHYDRO -1,4-BENZODIAZÉPINE-2-THIONES POUR LE TRAITEMENT DE MALADIES LIÉES AU SNC
  申请人：HOFFMANN LA ROCHE

  公开号：WO2018083051A1

  公开（公告）日：2018-05-11

  The present invention provides compounds that are muscarinic M1 receptor positive allosteric modulators (PAM) and useful in the treatment of diseases, mediated by the muscarinic M1 receptor, such as Alzheimer's disease, cognitive impairment, schizophrenia, pain or sleep disorders, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances.

  本发明提供了一类肌胆碱 M1 受体正向变构调节剂（PAM）化合物，可用于治疗由肌胆碱 M1 受体介导的疾病，如阿尔茨海默病、认知障碍、精神分裂症、疼痛或睡眠障碍，以及它们的制备、含有它们的制药组合物，以及它们作为治疗活性物质的用途。
• Lipase-Catalyzed Acetylation of 3-Substituted 2,3-Dihydro-1<i>H</i>-1,4-benzodiazepin-2-ones: Effect of temperature and conformation on enantioselectivity and configuration
  作者：Amir Avdagić、Andreja Lesac、Zsuzsa Majer、Miklòs Hollòsi、Vitomir Šunjić

  DOI：10.1002/hlca.19980810558

  日期：——

  due to the binding to the enzyme, in absolute (P)-conformation. Temperature dependence of enantioselectivity revealed inverse correlation of the E value of rac-9, and ee values for prochiral 16, with T[K], indicating prevalent contribution of the enthalpy term to enantioselection. Absolute conformation (M/P) and absolute configuration at C(3) of all products was determined by combining CD and 1H-NMR

  由醋酸乙烯酯/ AcOEt中通过固定化的催化乙酰化的对映选择性南极假丝酵母脂肪酶（诺维信435）。研究了外消旋-3-（羟甲基）-1,4-苯并二氮杂-2-酮7，9，14（Ñ数目; = 1 CH 2基团在链中的C（3）），20（n = 2）和前手性3,3-双（羟甲基）衍生物16。对映体过量（ee [％]）与底物的构象特性（相对构象，两个船状基态构象之间的能量差，环反转势垒）相关，如DNMR和MM2计算所确定。优先形成乙酸酯（+）- 8，（+）- 10，（+）- 15和（+）- 21的（3S）-对映体。在乙酸盐（-）- 17（ee 90.2％）的情况下，有利于（3R）-对映异构体的形成。在rac - 3（n = 0）中具有类人血样特性的C（3）OH基团不能被23种测试的脂肪酶和4种酯酶中的任何一种乙酰化。外消旋醇7，9，14，和20，优选的acetylationof（3小号） -对映体，存在于绝
• 1,3-dihydro-1,4-benzodiazepine-2-thiones for the treatment of CNS related diseases
  申请人：Hoffmann-La Roche Inc.

  公开号：US11021448B2

  公开（公告）日：2021-06-01

  The present invention provides compounds that are muscarinic M1 receptor positive allosteric modulators (PAM) and useful in the treatment of diseases, mediated by the muscarinic M1 receptor, such as Alzheimer's disease, cognitive impairment, schizophrenia, pain or sleep disorders, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances.

  本发明提供的化合物是毒蕈碱 M1 受体正性异位调节剂 (PAM)，可用于治疗由毒蕈碱 M1 受体介导的疾病，如阿尔茨海默氏症、认知障碍、精神分裂症、疼痛或睡眠障碍；本发明还提供了这些化合物的制造方法、含有这些化合物的药物组合物及其作为治疗活性物质的用途。
• 1,3-DIHYDRO-1,4-BENZODIAZEPINE-2-THIONES FOR THE TREATMENT OF CNS RELATED DISEASES
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3535253A1

  公开（公告）日：2019-09-11
• Discrimination between Enantiomers of Structurally Related Molecules:  Separation of Benzodiazepines by Molecularly Imprinted Polymers
  作者：Bradley R. Hart、Daniel J. Rush、Kenneth J. Shea

  DOI：10.1021/ja9926313

  日期：2000.1.1

  Molecular imprinting has been used to create synthetic receptor sites for a series of chiral benzodiazepines. A detailed HPLC analysis of binding properties using molecularly imprinted polymers (MIPs) as the stationary phase showed that binding, as measured by chromatographic retention, shows significant dependence on the chiral match or mismatch. In addition, the shape and spatial orientation of functionality of the imprinted binding site is also critical for recognition. Imprinted polymers, therefore, are not only able to discriminate between enantiomers of the imprinted molecule, they also demonstrate an ability to discriminate between a wide range of enantiomers of structurally related molecules that have not been imprinted. The ability of MIPs to discriminate between enantiomers of molecules in favor of the imprinted absolute configuration, even as the structural homology between the enantiomers and the original template decreases, indicates that the synthetic benzodiazepine receptors may serve as crude mimics of the natural receptor.