4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepine]-2'-ylamino)-3-fluorobenzoic acid | 1137213-46-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 嘧啶二氮卓类
• 英文名称: 4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepine]-2'-ylamino)-3-fluorobenzoic acid
• 英文别名: 4-[(9-cyclopentyl-5-methyl-6-oxospiro[8H-pyrimido[4,5-b][1,4]diazepine-7,1'-cyclobutane]-2-yl)amino]-3-fluorobenzoic acid
• CAS: 1137213-46-7
• 化学式: C₂₃H₂₆FN₅O₃
• 分子量: 439.49
• InChiKey: TVQPXOXHIHPBHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-氨基-4-甲基哌嗪 、 4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepine]-2'-ylamino)-3-fluorobenzoic acid 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepine]-2'-ylamino)-3-fluoro-N-(4-methylpiperazin-1-yl)benzamide
  参考文献：
  名称：

  [EN] PYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
  [FR] DÉRIVÉS DE PYRIMIDINE COMME INHIBITEURS DE PROTÉINE KINASES

  摘要：

  本发明涉及公式(VII)I的化合物，或其药学上可接受的盐或酯，其中：X为NR7；Y为O或N-(CH2)nR19；n为1、2或3；m为1或2；R1和R2分别独立地为H、烷基或环烷基；R4和R4'分别独立地为H或烷基；或者R4和R4'一起形成螺环烷基基团；R19为H、烷基、芳基或环烷基基团；R6为OR8或卤素；而R7和R8各自独立地为H或烷基。进一步方面涉及包括上述化合物的药物组合物以及其在治疗增殖性疾病等方面的用途。

  公开号：

  WO2009040556A1
• 作为产物：
  描述：

  2'-chloro-9'-cyclopentyl-5'-methyl-8',9'-dihydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepin]-6'(5'H)-one 、 3-氟-4-氨基苯甲酸 在 三氟乙酸 作用下， 以 2,2,2-三氟乙醇 为溶剂， 反应 138.0h， 以55%的产率得到4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepine]-2'-ylamino)-3-fluorobenzoic acid
  参考文献：
  名称：

  [EN] PYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
  [FR] DÉRIVÉS DE PYRIMIDINE COMME INHIBITEURS DE PROTÉINE KINASES

  摘要：

  本发明涉及公式(VII)I的化合物，或其药学上可接受的盐或酯，其中：X为NR7；Y为O或N-(CH2)nR19；n为1、2或3；m为1或2；R1和R2分别独立地为H、烷基或环烷基；R4和R4'分别独立地为H或烷基；或者R4和R4'一起形成螺环烷基基团；R19为H、烷基、芳基或环烷基基团；R6为OR8或卤素；而R7和R8各自独立地为H或烷基。进一步方面涉及包括上述化合物的药物组合物以及其在治疗增殖性疾病等方面的用途。

  公开号：

  WO2009040556A1

文献信息

• STRAIGHTFORWARD ENTRY TO 7-AZABICYCLO[2.2.1]HEPTANE-1-CARBONITRILES AND SUBSEQUENT SYNTHESIS OF EPIBATIDINE ANALOGUES
  申请人：STEVENS Christian

  公开号：US20090275616A1

  公开（公告）日：2009-11-05

  The present invention relates to a group of substituted-7-azabicyclo-[2.2.1]heptyl derivatives with biological activity. The present invention also relates to synthetic methods for producing said substituted-7-azabicyclo-[2.2.1]heptyl derivatives. The present invention also relates to certain intermediates for producing such substituted-7-azabicyclo-[2.2.1]heptyl derivatives, as well as a synthetic method for producing such intermediates. The present invention also relates to pharmaceutical compositions comprising such substituted-7-azabicyclo-[2.2.1]heptyl derivatives, as well as their use as medicaments for the treatment of diseases mediated by a Nicotinic Acetylcholine Receptor or a receptor being a member of the Neurotransmitter-gated Ion Channel Superfamily, such as pain, Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy and nicotine addiction.

  本发明涉及一组具有生物活性的取代-7-氮杂双环[2.2.1]庚基衍生物。本发明还涉及用于制备所述取代-7-氮杂双环[2.2.1]庚基衍生物的合成方法。本发明还涉及用于制备此类取代-7-氮杂双环[2.2.1]庚基衍生物的某些中间体，以及用于制备此类中间体的合成方法。本发明还涉及包含此类取代-7-氮杂双环[2.2.1]庚基衍生物的药物组合物，以及它们作为治疗由尼古丁乙酰胆碱受体或神经递质门控离子通道超家族成员介导的疾病的药物的用途，如疼痛、阿尔茨海默病、帕金森病、精神分裂症、癫痫和尼古丁成瘾。
• SUBSTITUTED 7-AZABICYCLO[2.2.1]HEPTYL DERIVATIVES USEFUL FOR MAKING PHARMACEUTICAL COMPOSITIONS
  申请人：STEVENS Christian

  公开号：US20100093807A1

  公开（公告）日：2010-04-15

  This invention provides 1-substituted-7-azabicyclo[2.2.1]heptyl derivatives, intermediates and methods for producing them, which are therapeutic agents useful for the prevention and treatment of central nervous system disorders and diseases mediated by a Nicotinic Acetylcholine Receptor such as Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy, pain, nicotine addiction and dementia.

  这项发明提供了1-取代-7-氮杂双环[2.2.1]庚基衍生物、中间体及其制备方法，这些治疗剂对预防和治疗由尼古丁乙酰胆碱受体介导的中枢神经系统疾病和疾病，如阿尔茨海默病、帕金森病、精神分裂症、癫痫、疼痛、尼古丁成瘾和痴呆症非常有用。
• PYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
  申请人：Hollick Jonathan James

  公开号：US20110046093A1

  公开（公告）日：2011-02-24

  The present invention relates to a compound of formula (VII)I, or a pharmaceutically acceptable salt or ester thereof, wherein: X is NR 7 ; Y is O or N—(CH 2 ) n R 19 ; n is 1, 2 or 3; m is 1 or 2; R 1 and R 2 are each independently H, alkyl or cycloalkyl; R 4 and R 4′ each independently H alkyl; or R 4 and R 4′ together form a spiro cycloalkyl group; R 19 is H, alkyl, aryl or a cycloalkyl group; R 6 is OR 8 or halogen; and R 7 and R 8 are each independently H or alkyl. Further aspects relate to pharmaceutical compositions comprising said compounds and use therefore in the treatment of proliferative disorders and the like.

  本发明涉及一种化合物，其化学式为(VII)I，或其药学上可接受的盐或酯，其中：X为NR7；Y为O或N-(CH2)nR19；n为1、2或3；m为1或2；R1和R2各自独立地为H、烷基或环烷基；R4和R4′各自独立地为H烷基；或R4和R4′共同形成一个螺环烷基；R19为H、烷基、芳基或环烷基；R6为OR8或卤素；R7和R8各自独立地为H或烷基。此外，该发明还涉及包含上述化合物的制药组合物以及其在治疗增生性疾病等方面的用途。
• Pyrimidine derivatives as protein kinase inhibitors
  申请人：Hollick Jonathan James

  公开号：US08563542B2

  公开（公告）日：2013-10-22

  The present invention relates to a compound of formula (VII)I, or a pharmaceutically acceptable salt or ester thereof, wherein: X is NR7; Y is O or N—(CH2)nR19; n is 1, 2 or 3; m is 1 or 2; R1 and R2 are each independently H, alkyl or cycloalkyl; R4 and R4′ each independently H alkyl; or R4 and R4′ together form a spiro cycloalkyl group; R19 is H, alkyl, aryl or a cycloalkyl group; R6 is OR8 or halogen; and R7 and R8 are each independently H or alkyl. Further aspects relate to pharmaceutical compositions comprising said compounds and use therefore in the treatment of proliferative disorders and the like.

  本发明涉及化合物式（VII）I，或其药学上可接受的盐或酯，其中：X是NR7；Y是O或N-（CH2）nR19；n为1、2或3；m为1或2；R1和R2分别独立地是氢、烷基或环烷基；R4和R4'分别独立地是氢、烷基；或者R4和R4'共同形成一个螺环烷基；R19是氢、烷基、芳基或环烷基；R6是OR8或卤素；R7和R8分别独立地是氢或烷基。另外，本发明还涉及包括所述化合物的制药组合物，并将其用于治疗增生性疾病等。
• LIGANDS FOR RHODIUM CATALYZED REDUCTIVE CARBONYLATION OF ALCOHOLS
  申请人：DOW GLOBAL TECHNOLOGIES LLC

  公开号：US20150025280A1

  公开（公告）日：2015-01-22

  A catalytic system for reductive carbonylation of an alcohol that includes a rhodium complex, an iodide-containing catalyst promoter, and a supporting phosphorus-containing bidentate ligand for the rhodium complex containing at least one aromatic substituent covalently attached to at least one phosphorus of the supporting phosphorus-containing bidentate ligand in an ortho position with an alkoxy substituent or an aryloxy substituent.

  一种还原羰基化醇的催化体系，包括一个铑配合物、含碘催化剂促进剂和支撑磷双齿配体，其中铑配合物至少含有一个芳基取代基共价连接到支持磷双齿配体的至少一个磷原子的邻位，其具有烷氧基取代基或芳氧基取代基。