((R)-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)carbamic acid tert-butyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: ((R)-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl (R)-(4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxozepin-3-yl)carbamate；(R)-3-(tert-butoxycarbonyl-amino)-2,3-dihydro-1,5-benzoxazepin-4-one；((R)-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-carbamic acid tert-butyl ester；tert-butyl N-[(3R)-4-oxo-3,5-dihydro-2H-1,5-benzoxazepin-3-yl]carbamate
• 化学式: C₁₄H₁₈N₂O₄
• 分子量: 278.308
• InChiKey: STPHEUUFTOGKNY-SNVBAGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ((R)-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)carbamic acid tert-butyl ester 在 盐酸 、 氢氧化钾 、 四丁基溴化铵 、 乙酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 (+)-(R)-4-(3-{3-[8-oxo-9-(2-oxo-2-pyrrolidin-1-ylethyl)-6,7,8,9-tetrahydro-5-oxa-9-azabenzocyclohepten-7-yl]ureido}benzyloxycarbonylamino)butyric acid methyl ester
  参考文献：
  名称：

  Synthesis and structure-activity relationships of dual histamine H2 and gastrin receptor antagonists with modified benzodiazepine skeletons

  摘要：

  Three different types of dual histamine H-2 and gastrin receptor antagonists, e.g. those bearing a benzazepine, benzoxazepine, or benzothiazepine skeleton instead of the benzodiazepine one as a gastrin receptor antagonistic moiety were synthesized to reduce high hydrophobicity of parent compounds and evaluated for the dual activities. These skeletal modifications significantly potentiated the binding affinity of dual antagonists with histamine H-2, receptor but markedly diminished their binding affinity with the gastrin receptor and the gastrin versus CCK-A receptor selectivity. We evaluated in vivo gastric acid antisecretory activities for some representative compounds by the rat pylorus ligation method for 10 mg kg(-1) dose by oral route. However, they exerted only low inhibitory activities for oral dose with % inhibition values ranging between 32 and 53%. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00075-8
• 作为产物：
  描述：

  1-氟-2-硝基苯 在 palladium on activated charcoal 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.5h， 生成 ((R)-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)carbamic acid tert-butyl ester
  参考文献：
  名称：

  벤조[b][1,4]옥사제핀 유도체 및 이를 유효성분으로 포함하는 키나아제 관련 질환 치료용 약학적 조성물

  摘要：

  这是关于含有苯并[b][1,4]氧杂喹啉衍生物和其作为有效成分的治疗激酶相关疾病的药学组合物的内容，本发明提供的苯并[b][1,4]氧杂喹啉衍生物在一方面具有对ABL1、ABL2、AURKB、BRK、CDK11、CDK8、CDK9、CDKL2、CIT、DDR1、FLT3、FLT3、HIPK4、HUNK、JAK3、KIT、LOK、LTK、MET、MET、MLK2、MUSK、MYO3A、PAK3、PCTK3、PDGFRA、PDGFRB、RIPK1、TIE1和ZAK等一种或多种激酶的优异抑制活性，因此可用作激酶相关疾病的治疗药物。

  公开号：

  KR20200088945A

文献信息

• 벤조[b][1,4]옥사제핀 유도체 및 이를 유효성분으로 포함하는 키나아제 관련 질환 치료용 약학적 조성물
  申请人：VoronoiBio Inc. 보로노이바이오 주식회사(120180136950) Corp. No ▼ 120111-0875859BRN ▼146-81-00829

  公开号：KR20200088945A

  公开（公告）日：2020-07-24

  벤조[b][1,4]옥사제핀 유도체 및 이를 유효성분으로 포함하는 키나아제 관련 질환 치료용 약학적 조성물에 관한 것으로, 본 발명의 일 측면에서 제공하는 벤조[b][1,4]옥사제핀 유도체는 ABL1, ABL2, AURKB, BRK, CDK11, CDK8, CDK9, CDKL2, CIT, DDR1, FLT3, FLT3, HIPK4, HUNK, JAK3, KIT, LOK, LTK, MET, MET, MLK2, MUSK, MYO3A, PAK3, PCTK3, PDGFRA, PDGFRB, RIPK1, TIE1 및 ZAK으로 이루어지는 군으로부터 선택되는 1종 이상의 키나아제에 대해 우수한 억제 활성을 나타내므로, 키나아제 관련 질환의 치료제로 사용 가능한 효과가 있다.

  这是关于含有苯并[b][1,4]氧杂喹啉衍生物和其作为有效成分的治疗激酶相关疾病的药学组合物的内容，本发明提供的苯并[b][1,4]氧杂喹啉衍生物在一方面具有对ABL1、ABL2、AURKB、BRK、CDK11、CDK8、CDK9、CDKL2、CIT、DDR1、FLT3、FLT3、HIPK4、HUNK、JAK3、KIT、LOK、LTK、MET、MET、MLK2、MUSK、MYO3A、PAK3、PCTK3、PDGFRA、PDGFRB、RIPK1、TIE1和ZAK等一种或多种激酶的优异抑制活性，因此可用作激酶相关疾病的治疗药物。
• Benzazepinone derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05610153A1

  公开（公告）日：1997-03-11

  The invention relates to substituted 3-amino-1-arylalkyl-benzazepin-2-ones of the general formula ##STR1## wherein Ar is aryl; X is --O-- or --S(O).sub.n -- and n is 0, 1 or 2; X.sub.1 is C.sub.1 -C.sub.2 alkylene or a direct bond; R.sub.1 is hydrogen, lower alkyl, aryl-lower alkyl or acyl; R.sub.2 is lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, aryl-lower alkoxy-lower alkyl, aryl-lower alkyl or C.sub.3 -C.sub.7 cycloalkyl-lower alkyl; R.sub.3 is carboxy; lower alkoxycarbonyl; lower alkoxy-lower alkoxycarbonyl; aryl-lower alkoxycarbonyl; aryloxycarbonyl; carbamoyl; carbamoyl that (i) is monosubstituted by hydroxy, lower alkanesulfonyl, halo-lower alkanesulfonyl or by arylsulfonyl, (ii) is monosubstituted or disubstituted, the substituents being independent of one another, by lower alkyl, lower alkenyl, lower alkynyl or by phenyl-lower alkyl or (iii) is disubstituted by lower alkylene or by lower alkylene-Z.sub.1 -lower alkylene, Z.sub.1 being O, S or NH; 5-tetrazolyl; PO.sub.2 H.sub.2 ; PO.sub.3 H.sub.2 or SO.sub.3 H.sub.2 ; the ring A and aromatic radicals are, independently of one another, unsubstituted or mono- or poly-substituted by substituents selected from the group consisting of: lower alkyl, aryl-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy, aryl-lower alkoxy, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloalkyl-lower alkyl, nitro, halogen, trifluoromethyl, amino and amino that is monosubstituted or disubstituted, the substituents being independent of one another, by lower alkyl, aryl-lower alkyl or by aryl, or disubstituted by lower alkylene or by lower alkyleneoxy-lower alkylene; or a salt thereof; to processes for the preparation thereof; and to the use thereof as well as to pharmaceutical compositions that comprise compounds of formula (I) or pharmaceutically acceptable salts thereof.

  本发明涉及通式##STR1##中的替代3-氨基-1-芳基烷基-苯并[2,3-d]蒽-2-酮，其中Ar为芳基；X为--O--或--S(O).sub.n--，n为0、1或2；X.sub.1为C.sub.1-C.sub.2烷基或直接键；R.sub.1为氢、较低烷基、芳基-较低烷基或酰基；R.sub.2为较低烷基、羟基-较低烷基、较低烷氧基-较低烷基、芳基-较低烷氧基-较低烷基、芳基-较低烷基或C.sub.3-C.sub.7环烷基-较低烷基；R.sub.3为羧基；较低烷氧羰基；较低烷氧-较低烷氧羰基；芳基-较低烷氧羰基；芳氧羰基；氨基；氨基，其(i)被羟基、较低烷磺酰基、卤代较低烷磺酰基或芳基磺酰基单取代，(ii)被较低烷基、较低烯基、较低炔基或苯基-较低烷基单取代或双取代，取代基相互独立，或(iii)被较低烷基二取代或较低烷基-Z.sub.1-较低烷基二取代，Z.sub.1为O、S或NH；5-四唑基；PO.sub.2H.sub.2；PO.sub.3H.sub.2或SO.sub.3H.sub.2；环A和芳基分别独立地未取代或单取代或多取代，取代基选自：较低烷基、芳基-较低烷基、较低烷氧基-较低烷基、较低烷氧基、较低烷氧-较低烷氧、芳基-较低烷氧、C.sub.3-C.sub.7环烷基、C.sub.3-C.sub.7环烷基-较低烷基、硝基、卤素、三氟甲基、氨基和氨基，氨基被较低烷基、芳基-较低烷基或芳基单取代或双取代，取代基相互独立，或被较低烷基或较低烷氧基-较低烷基双取代；或其盐；以及其制备方法；以及其用途，以及包含通式(I)化合物或其药学上可接受的盐的药物组合物。
• Benzazepinone Nav1.7 blockers: Potential treatments for neuropathic pain
  作者：Scott B. Hoyt、Clare London、Hyun Ok、Edward Gonzalez、Joseph L. Duffy、Catherine Abbadie、Brian Dean、John P. Felix、Maria L. Garcia、Nina Jochnowitz、Bindhu V. Karanam、Xiaohua Li、Kathryn A. Lyons、Erin McGowan、D. Euan MacIntyre、William J. Martin、Birgit T. Priest、McHardy M. Smith、Richard Tschirret-Guth、Vivien A. Warren、Brande S. Williams、Gregory J. Kaczorowski、William H. Parsons

  DOI：10.1016/j.bmcl.2007.09.032

  日期：2007.11

  A series of benzazepinones were synthesized and evaluated as hNa(v)1.7 sodium channel blockers. Several compounds from this series displayed good oral bioavailability and exposure and were efficacious in a rat model of neuropathic pain.

  合成了一系列苯并ze庚酮，并将其评估为hNa（v）1.7钠通道阻滞剂。该系列中的几种化合物具有良好的口服生物利用度和暴露能力，并且在神经性疼痛的大鼠模型中有效。
• Substituted Benzodiazepinones, Benzoxazepinones and Benzothiazepinones as Sodium Channel Blockers
  申请人：Hoyt Scott B.

  公开号：US20100144715A1

  公开（公告）日：2010-06-10

  The present invention is directed to substituted benzodiazepinones, benzoxazepinones and benzothiazepinones compounds that are sodium channel blockers useful for the treatment of chronic and neuropathic pain. The compounds of the present invention are also useful for the treatment of other conditions, including disorders of the CNS such as anxiety, depression, epilepsy, manic depression and bipolar disorder. This invention also provides pharmaceutical compositions comprising a compound of the present invention, either alone, or in combination with one or more therapeutically active compounds, and a pharmaceutically acceptable carrier. This invention further comprises methods for the treatment of acute pain, chronic pain, visceral pain, inflammatory pain, neuropathic pain and disorders of the CNS including, but not limited to, epilepsy, manic depression, depression, anxiety and bipolar disorder comprising administering the compounds and pharmaceutical compositions of the present invention.

  本发明涉及替代苯二氮平酮、苯并噁唑酮和苯并噻唑酮化合物，它们是钠通道阻滞剂，可用于治疗慢性和神经病理性疼痛。本发明的化合物也可用于治疗其他疾病，包括中枢神经系统紊乱，如焦虑、抑郁、癫痫、躁郁症和双相障碍。本发明还提供了含有本发明化合物的药物组合物，可以单独使用或与一个或多个治疗活性化合物组合使用，并与药学上可接受的载体一起使用。本发明还包括治疗急性疼痛、慢性疼痛、内脏疼痛、炎症性疼痛、神经病理性疼痛和中枢神经系统紊乱的方法，包括但不限于癫痫、躁郁症、抑郁症、焦虑症和双相障碍，通过给予本发明的化合物和药物组合物进行治疗。
• WO2008/106077
  申请人：——

  公开号：——

  公开（公告）日：——