N-(5,6,7,8-tetrahydro-6,8,8-trimethyl[1,6]naphthyridin-3yl)-3-cyano-4-methoxybenzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-(5,6,7,8-tetrahydro-6,8,8-trimethyl[1,6]naphthyridin-3yl)-3-cyano-4-methoxybenzamide
• 英文别名: 3-cyano-4-methoxy-N-(6,8,8-trimethyl-5,7-dihydro-1,6-naphthyridin-3-yl)benzamide
• 化学式: C₂₀H₂₂N₄O₂
• 分子量: 350.42
• InChiKey: RBWYYNWSVMSBAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-amino-6,8,8-trimethyl-5,6,7,8-tetrahydro[1,6]naphthyridine 、 3-氰基-4-甲氧基苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 N-(5,6,7,8-tetrahydro-6,8,8-trimethyl[1,6]naphthyridin-3yl)-3-cyano-4-methoxybenzamide
  参考文献：
  名称：

  The design of 8,8-Dimethyl[1,6]naphthyridines as potential anticonvulsant agents

  摘要：

  Starting from a series of 7-linked tetrahydroisoquinoline derivatives, as exemplified by SB-270664, a new series of 8,8-dimethylnaphthyridine compounds has been identified. SAR studies around these attractive leads have provided compounds such as 12 which display excellent anticonvulsant activity and an encouraging pharmacokinetic profile in vivo. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00288-9

文献信息

• Tetrahydronaphthyridinyl-carboxamides having anti-convulsant activity
  申请人：SmithKline Beecham p.l.c.

  公开号：US20020143029A1

  公开（公告）日：2002-10-03

  Compounds of formula (I) and pharmaceutically acceptable salts and solvates: 1 where R 1 is hydrogen, C 1-6 alkyl (optionally substituted by hydroxy or C 1-4 alkoxy), phenyl-C 1-4 alkyl-, C 1-6 alkenyl, C 1-6 alkynyl; R 2 is hydrogen or up to three substituents selected from halogen, NO 2 , CN, N 3 , CF 3 O—, CF 3 S—, CF 3 CO—, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, C 1-6 perfluoroalkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl-, C 1-6 alkylO—, C 1-6 alkylCO—, C 3-6 cycloalkylO—, C 3-6 cycloalkylCO—, C 3-6 cycloalkyl-C 1-4 alkylO—, C 3-6 cycloalkyl-C 1-4 alkylCO—, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C 1-4 alkyl-, C 1-6 alkylS—, C 1-6 alkylSO 2 —, (C 1-4 alkyl) 2 NSO 2 —, (C 1-4 alkyl)NHSO 2 —, (C 1-4 alkyl) 2 NCO—, (C 1-4 alkyl)NHCO— or CONH 2 ; or —NR 5 R 6 where R 5 is hydrogen or C 1-4 alkyl, and R 6 is hydrogen, C 1-4 alkyl, formyl, —CO 2 C 1-4 alkyl or —COC 1-4 alkyl; or two R 2 groups together form a carbocyclic ring that is saturated or unsaturated. R 3 groups and R 4 groups are each independently hydrogen or C 1-6 alkyl and/or the two R 3 groups and/or the two R 4 groups together form a C 3-6 spiroalkyl group, provided that at least one R 3 or R 4 group is not hydrogen; and X is selected from hydrogen, halogen, cyano, alkyl and alkoxy. are useful in the treatment and prophylaxis of epilepsy, migraine, and other disorders.

  公式（I）化合物及其药学上可接受的盐和溶剂化合物：其中R1为氢、C1-6烷基（可选地被羟基或C1-4烷氧基取代）、苯基-C1-4烷基、C1-6烯基、C1-6炔基；R2为氢或最多三个取代基，所选自卤素、NO2、CN、N3、CF3O—、CF3S—、CF3CO—、C1-6烷基、C1-6烯基、C1-6炔基、C1-6全氟烷基、C3-6环烷基、C3-6环烷基-C1-4烷基、C1-6烷氧基、C1-6烷基CO—、C3-6环烷基烷氧基、C3-6环烷基CO—、C3-6环烷基-C1-4烷氧基、C3-6环烷基-C1-4烷基CO—、苯基、苯氧基、苄氧基、苯甲酰基、苯基-C1-4烷基、C1-6烷基S—、C1-6烷基SO2—、（C1-4烷基）2NSO2—、（C1-4烷基）NHSO2—、（C1-4烷基）2NCO—、（C1-4烷基）NHCO—或CONH2；或—NR5R6，其中R5为氢或C1-4烷基，R6为氢、C1-4烷基、甲酰基、—CO2C1-4烷基或—COC1-4烷基；或两个R2基共同形成一个饱和或不饱和的碳环。R3基和R4基各自独立地为氢或C1-6烷基，或两个R3基和/或两个R4基共同形成一个C3-6螺环烷基，前提是至少有一个R3或R4基不是氢；X选自氢、卤素、氰基、烷基和烷氧基。这些化合物对于治疗和预防癫痫、偏头痛和其他疾病是有用的。
• TETRAHYDRONAPHTHYRIDINYL-CARBOXAMIDES HAVING ANTI-CONVULSANT ACTIVITY
  申请人：SmithKline Beecham plc

  公开号：EP1084122B1

  公开（公告）日：2003-10-22
• US6410555B1
  申请人：——

  公开号：US6410555B1

  公开（公告）日：2002-06-25
• US6762192B2
  申请人：——

  公开号：US6762192B2

  公开（公告）日：2004-07-13
• The design of 8,8-Dimethyl[1,6]naphthyridines as potential anticonvulsant agents
  作者：Nigel E Austin、Michael S Hadley、John D Harling、Frank P Harrington、Gregor J Macdonald、Darren J Mitchell、Graham J Riley、Tania O Stean、Geoffrey Stemp、Sharon C Stratton、Mervyn Thompson、Neil Upton

  DOI：10.1016/s0960-894x(03)00288-9

  日期：2003.5

  Starting from a series of 7-linked tetrahydroisoquinoline derivatives, as exemplified by SB-270664, a new series of 8,8-dimethylnaphthyridine compounds has been identified. SAR studies around these attractive leads have provided compounds such as 12 which display excellent anticonvulsant activity and an encouraging pharmacokinetic profile in vivo. (C) 2003 Elsevier Science Ltd. All rights reserved.