(S)-Oxazepam | 40762-00-3

• 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: (S)-Oxazepam
• 英文别名: S-oxazepam；oxazepam；ZINC00000575；(3S)-7-chloro-3-hydroxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 40762-00-3
• 化学式: C₁₅H₁₁ClN₂O₂
• 分子量: 286.718
• InChiKey: ADIMAYPTOBDMTL-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  61.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-Oxazepam 以 乙醇 、 乙腈 为溶剂， 生成 舒宁
  参考文献：
  名称：

  对映体奥沙西ms的消旋动力学和对映体奥沙西m3-乙酸盐在大鼠肝微粒体和脑匀浆中的立体选择性水解。

  摘要：

  在装有Pirkle手性固定相的HPLC色谱柱上拆分奥沙西m的对映异构体和3-O-酰基，1-N-酰基-3-O-酰基和3-O-甲基醚衍生物的对映体。（R）-N-（3,5-二硝基苯甲酰基）苯基甘氨酸或（S）-N-（3,5-二硝基苯甲酰基）亮氨酸]通过离子键或共价键与γ-氨基丙基硅烷化二氧化硅的球形颗粒结合，并在装有聚-N-丙烯酰基-（S）-苯丙氨酸乙酯与硅胶共价键合（Chiraspher）。在所有测试的手性固定相上，使用不同溶剂组成的几种流动相和不同的色谱分辨率实现了分离。奥沙西m的拆分对映体经历消旋作用，而3-O-酰基和3-O-甲基衍生物的对映体是稳定的。奥沙西m对映异构体的消旋半衰期是通过在对映异构体拆分后立即（在30 s之内）在分光旋光仪上监测椭圆率随时间的变化来确定的，发现其变化取决于所使用的溶剂。通过简单而灵敏的CSP-HPLC方法测定了大鼠肝微粒体和大鼠脑匀浆中酯酶水解外消旋和对映体

  DOI：

  10.1002/jps.2600781002
• 作为产物：
  描述：

  舒宁 在 Chiralpak AGP column 作用下， 反应 0.5h， 生成 (-)3R-oxazepam 、 (S)-Oxazepam
  参考文献：
  名称：

  手性液相色谱-串联质谱法同时测定多种动物组织中的七种精神活性药物对映体

  摘要：

  在畜牧业中，非法使用抗精神病药已引起食品安全问题。本文首次提出了一种多残留的方法，可以同时对映选择性测定猪肉，牛肉和羔羊肌肉中的七种抗精神病药。研究了Chiralpak AGP对流动相中pH和有机改性剂变化的行为，并在30分钟内快速分离了所有分析物。所有对映异构体的校准曲线在1–250 ng g -1范围内均为线性，相关系数高于0.9931。目标化合物的回收率高于82.1％，重复性和中间精密度分别低于18.2％和17.4％。在三种基质中，检出限和定量限的范围为0.20至0.65 ng g -1和分别为0.40至1.00 ng g -1。所提出的方法可用于为手性抗精神病药的可靠风险评估提供更多信息。

  DOI：

  10.1016/j.foodchem.2019.125241

文献信息

• [EN] INDOLIN-2-ONE OR PYRROLO-PYRIDIN-2-ONE DERIVATIVES<br/>[FR] DÉRIVÉS D'INDOLIN-2-ONE OU DE PYRROLOPYRIDIN-2-ONE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015197567A1

  公开（公告）日：2015-12-30

  The present invention is concerned with 2-oxo-2,3-dihydro-indoles of general formula (I) wherein Ar1 is phenyl or a five or six membered heteroaryl group, containing one, two or three heteroatoms, selected from N, S or O, wherein the N-heteroatom in the heteroaryl group may be oxidized to N+-(O-); R1 is lower alkyl, halogen, cyano or cycloalkyl; Ar2 is a five or six membered heteroaryl group, containing one, two, three or four heteroatoms, selected from N, S or O, wherein the N-heteroatom in the heteroaryl group may be oxidized to N+-(O-), or is benzo[b]thiophenyl; R2 is hydrogen, lower alkyl, halogen, cyano, lower alkyl substituted by hydroxyl, lower alkyl substituted by halogen, lower alkyl substituted by amino, lower alkyl substituted by alkoxy, lower alkyl substituted by amide, or is cycloalkyl; X is CH or N; n is 1 or 2; m is 1 or 2; as well as with a pharmaceutically acceptable salt thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds may be used in the treatment of CNS diseases related to positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, neurodegenerative disease, sleep disturbances, chronic fatigue syndrome, stiffness, inflammatory disease, asthma, Huntington's disease, ADHD, amyotrophic lateral sclerosis, epilepsy, effects in arthritis, autoimmune disease, viral and fungal infections, cardiovascular diseases, ophthalmology and inflammatory retinal diseases and balance problems.

  本发明涉及一般式（I）的2-氧代-2,3-二氢吲哚，其中Ar1为苯基或含有一个、两个或三个异原子（N、S或O）的五元或六元杂环芳基，其中杂环芳基中的N-异原子可以被氧化为N+-(O-)；R1为低碳基、卤素、氰基或环烷基；Ar2为含有一个、两个、三个或四个异原子（N、S或O）的五元或六元杂环芳基，其中杂环芳基中的N-异原子可以被氧化为N+-(O-)，或者为苯并[ｂ]噻吩基；R2为氢、低碳基、卤素、氰基、被羟基取代的低碳基、被卤素取代的低碳基、被氨基取代的低碳基、被烷氧基取代的低碳基、被酰胺取代的低碳基，或者为环烷基；X为CH或N；n为1或2；m为1或2；以及其药学上可接受的盐、消旋体混合物、或其对映体和/或光学异构体和/或立体异构体。这些化合物可用于治疗与精神病（精神病）、精神分裂症的阳性和阴性症状、物质滥用、酒精和药物成瘾、强迫症、认知障碍、躁郁症、情感障碍、重度抑郁症、治疗难治性抑郁症、焦虑障碍、阿尔茨海默病、自闭症、帕金森病、慢性疼痛、边缘人格障碍、神经退行性疾病、睡眠障碍、慢性疲劳综合征、僵硬、炎症性疾病、哮喘、亨廷顿病、注意力缺陷多动障碍、肌萎缩侧索硬化症、癫痫、关节炎作用、自身免疫疾病、病毒和真菌感染、心血管疾病、眼科学和炎症性视网膜疾病以及平衡问题相关的中枢神经系统疾病的治疗。
• [EN] INDOLIN-2-ONE DERIVATIVES USEFUL IN THE TREATMENT OF CNS DISEASES<br/>[FR] DÉRIVÉS D'INDOLINE-2-ONE UTILES DANS LE TRAITEMENT DE MALADIES DU SYSTÈME NERVEUX CENTRAL
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017076932A1

  公开（公告）日：2017-05-11

  The present invention is concerned with indolin-2-one derivatives of general formula (I) wherein A is phenyl or a six membered heteroaryl group, containing one or two N atoms, selected from (II) R1 is S(0)2lower alkyl, S(0)2NR4R5, S(0)2cycloalkyl, S-lower alkyl or S(0)2-azetidin-l-yl; R4 and R5 are independently from each other hydrogen, lower alkyl or (CH2)2OCH3; or the group A-R1 may form together with two neighboring carbon atoms from the group A an additional fused ring, selected from (III) R 2 is hydrogen or cycloalkyl; R 3 is methyl or halogen; n is 1 or 2; X is N, N+0" or CH; --- the dotted line may be nothing or -CH2-; as well as with a pharmaceutically acceptable salt thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds may be used in the treatment of CNS diseases related to positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive- compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, neurodegenerative disease, sleep disturbances, chronic fatigue syndrome, stiffness, inflammatory disease, asthma, Huntington's disease, ADHD, amyotrophic lateral sclerosis, effects in arthritis, autoimmune disease, viral and fungal infections, cardiovascular diseases, ophthalmology and inflammatory retinal diseases and balance problems, epilepsy and neurodevelopmental disorders with co- morbid epilepsy.

  本发明涉及一种通式(I)的吲哚啉-2-酮衍生物，其中A为苯基或含有一个或两个N原子的六元杂环烃基，选自(II)中；R1为S(0)2较低烷基，S(0)2NR4R5，S(0)2环烷基，S-较低烷基或S(0)2-氮杂环丙烯基；R4和R5分别独立地为氢、较低烷基或(CH2)2OCH3；或者基团A-R1可以与基团A中的两个相邻碳原子一起形成一个来自(III)中选择的额外融合环；R2为氢或环烷基；R3为甲基或卤素；n为1或2；X为N、N+0"或CH；---虚线可以为无或- -；以及其药学上可接受的盐、外消旋混合物或其相应的对映体和/或光学异构体和/或立体异构体。这些化合物可用于治疗与精神病（精神病）、精神分裂症的阳性和阴性症状、物质滥用、酒精和药物成瘾、强迫-强迫性障碍、认知障碍、双相障碍、情绪障碍、重度抑郁症、治疗难治性抑郁症、焦虑障碍、阿尔茨海默病、自闭症、帕金森病、慢性疼痛、边缘人格障碍、神经退行性疾病、睡眠障碍、慢性疲劳综合征、僵硬、炎症性疾病、哮喘、亨廷顿病、注意力缺陷多动障碍、肌萎缩侧索硬化、关节炎效应、自身免疫疾病、病毒和真菌感染、心血管疾病、眼科学和炎症性视网膜疾病和平衡问题、癫痫和伴发癫痫的神经发育障碍相关的中枢神经系统疾病的治疗。
• [EN] INDOLIN-2-ONE DERIVATIVES FOR USE IN THE TREATMENT OF CNS AND RELATED DISORDERS<br/>[FR] DÉRIVÉS INDOLIN-2-ONE DESTINÉS À ÊTRE UTILISÉS DANS LE TRAITEMENT DU SNC ET DE TROUBLES APPARENTÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017076931A1

  公开（公告）日：2017-05-11

  The present invention is concerned with indolin-2-one derivatives of general formula (I) wherein A is phenyl or a six membered heteroaryl group, containing one or two N atoms, selected from or the oxygen atom may form together with two neighboring carbon atoms from the group A an additional fused ring, selected from or; R1 is hydrogen, lower alkyl, lower alkyl substitututed by halogen or oxetanyl; R2 is hydrogen, lower alkyl lower alkoxy, halogen or cycloalkyl; the dotted line is nothing or may be –CH2-; as well as with a pharmaceutically acceptable salt thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof. The compounds may be used in the treatment of CNS diseases related to positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive- compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, neurodegenerative disease, sleep disturbances, chronic fatigue syndrome, stiffness, inflammatory disease, asthma, Huntington's disease, ADHD, amyotrophic lateral sclerosis, effects in arthritis, autoimmune disease, viral and fungal infections, cardiovascular diseases, ophthalmology and inflammatory retinal diseases and balance problems, epilepsy and neurodevelopmental disorders with co morbid epilepsy.

  本发明涉及一般式（I）中的吲哚啉-2-酮衍生物，其中A是苯基或含有一个或两个N原子的六元杂环基，选择自或氧原子可与基团A中的两个相邻碳原子形成一个额外的融合环，选择自或；R1是氢、较低烷基、受卤素或氧乙烯基取代的较低烷基；R2是氢、较低烷基、较低烷氧基、卤素或环烷基；虚线是不存在或可能是-CH2-；以及其药学上可接受的盐、消旋混合物、相应的对映体和/或光学异构体和/或立体异构体。这些化合物可用于治疗与精神病（精神病）、精神分裂症的阳性和阴性症状、物质滥用、酒精和药物成瘾、强迫症、认知障碍、躁郁症、情感障碍、重度抑郁症、治疗难治性抑郁症、焦虑症、阿尔茨海默病、自闭症、帕金森病、慢性疼痛、边缘人格障碍、神经退行性疾病、睡眠障碍、慢性疲劳综合征、僵硬、炎症性疾病、哮喘、亨廷顿病、注意缺陷多动障碍、肌萎缩侧索硬化、关节炎、自身免疫疾病、病毒和真菌感染、心血管疾病、眼科学和炎症性视网膜疾病以及平衡问题、癫痫和伴发癫痫的神经发育障碍相关的中枢神经系统疾病的治疗。
• [EN] INDOLIN-2-ONE AND 1,3-DIHYDRO-PYRROLO[3,2-c]PYRIDIN-2-ONE DERIVATIVES<br/>[FR] DÉRIVÉS D'INDOLIN-2-ONE ET DE 1,3-DIHYDRO-PYRROLO[3,2-C]PYRIDIN-2-ONE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015177110A1

  公开（公告）日：2015-11-26

  The present invention is concerned with indolin-2-one and l,3-dihydro-pyrrolo[3,2-c]pyridin-2-one derivatives of general formula (I) wherein Ar1 is phenyl, pyridinyl or pyrimidinyl; Ar2 is a 5 or 6 membered heteroaryl group, containing 2 or 3 heteroatoms, selected from N, O or S; R1 is hydrogen, lower alkyl, halogen or lower alkoxy; R2 is hydrogen or lower alkyl; R3 is hydrogen, lower alkyl, lower alkyl substituted by hydroxy, cycloalkyl, oxetan-3-yl, pyridinyl, imidazolyl, pyrazolyl, pyrimidinyl, which rings may optionally substituted by lower alkyl, or is -(CH2)3-S(O)2-cyclopropyl; X is CH or N; n is 1 or 2; as well as with a pharmaceutically acceptable salts thereof, with a racemic mixture, or with its corresponding enantiomer and/or optical isomer and/or stereoisomer thereof, for use in the treatment of certain central nervous system disorders which are positive (psychosis) and negative symptoms of schizophrenia, substance abuse, alcohol and drug addiction, obsessive-compulsive disorders, cognitive impairment, bipolar disorders, mood disorders, major depression, treatment resistant depression, anxiety disorders, Alzheimer's disease, autism, Parkinson's disease, chronic pain, borderline personality disorder, sleep disturbances, chronic fatigue syndrome, stiffness, antiinflammatory effects in arthritis and balance problems.

  本发明涉及一般式(I)的吲哚啉-2-酮和1,3-二氢吡咯并[3,2-c]吡啶-2-酮衍生物，其中Ar1是苯基、吡啶基或嘧啶基；Ar2是含有2个或3个N、O或S杂原子的5或6元杂芳基团；R1是氢、低碳基、卤素或低烷氧基；R2是氢或低碳基；R3是氢、低碳基、低碳基取代的羟基、环烷基、氧杂环丙烯基、吡啶基、咪唑基、吡唑基、嘧啶基，这些环可能被低碳基取代，或者是-(CH2)3-S(O)2-环丙基；X是CH或N；n为1或2；以及其药学上可接受的盐、消旋混合物、对映体和/或光学异构体和/或立体异构体，用于治疗某些中枢神经系统疾病，包括精神病（正性症状和负性症状）、精神分裂症、物质滥用、酒精和药物成瘾、强迫症、认知障碍、双相情感障碍、情绪障碍、重度抑郁症、治疗难治性抑郁症、焦虑症、阿尔茨海默病、自闭症、帕金森病、慢性疼痛、边缘性人格障碍、睡眠障碍、慢性疲劳综合征、僵硬、关节炎中的抗炎作用和平衡问题。
• Use of biocompatible polymers for the preparation of a composition or a medical device
  申请人：Barritault Denis

  公开号：US20070141020A1

  公开（公告）日：2007-06-21

  The invention relates to a biocompatible polymer having general formula (I) AaXxYy, wherein: A denotes a monomer; X denotes an RCOOR′ group; Y denotes an O or N-sulphonate group which is fixed to A and which has either formula —ROS03R′ or —RNS03R′ in which R denotes an optionally branched and/or unsaturated aliphatic hydrocarbon chain which can contain one or more aromatic rings and R′ denotes a hydrogen atom or a cation; a denotes the number of monomers; x denotes the rate of substitution of the A monomers by the X groups; and y denotes the rate of substitution of the A monomers by the Y groups. More specifically, the invention relates to the use of said biocompatible polymers for the preparation of a pharmaceutical, dermatological or cosmetic composition or a medical device, which are intended to prevent, relieve and/or treat discomfort, distress, itches, irritations and/or pain and/or to protect tissues against same. In addition, in certain cases, the use of said biocompatible polymers for pain treatment can impact on the actual curing of certain diseases. Significant improvements and even cures have been observed in relation to chronic and painful diseases that are associated with alterations in the extracellular matrix regardless of the origin thereof.

  该发明涉及具有通式（I）AaXxYy的生物相容性聚合物，其中：A表示单体；X表示一个RCOOR′基团；Y表示固定在A上的O或N-磺酸盐基团，其具有以下式之一：—ROS03R′或—RNS03R′，其中R表示可选的支链和/或不饱和的脂肪烃链，可以含有一个或多个芳香环，R′表示氢原子或阳离子；a表示单体的数量；x表示A单体被X基团取代的速率；y表示A单体被Y基团取代的速率。更具体地，该发明涉及利用所述生物相容性聚合物制备用于预防、缓解和/或治疗不适、痛苦、瘙痒、刺激和/或疼痛的药物、皮肤科或化妆品组合物或医疗器械，以及用于保护组织免受同样问题的影响。此外，在某些情况下，利用所述生物相容性聚合物进行疼痛治疗可能会影响某些疾病的实际治愈。在与细胞外基质变化相关的慢性疾病方面观察到了显著的改善甚至治愈。