N-[(3S,4S)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-yl]-2-chlorobenzamide | 157336-87-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-[(3S,4S)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-yl]-2-chlorobenzamide
• 英文别名: N-[(3S,4S)-6-Acetyl-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl]-2-chlorobenzamide；N-[(3S,4S)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-2-chlorobenzamide
• CAS: 157336-87-3
• 化学式: C₂₀H₂₀ClNO₄
• 分子量: 373.836
• InChiKey: KMBXNPJEKNKOQQ-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-[(3S,4S)-4-amino-3-hydroxy-2,2-dimethyl-3,4-dihydro-2 H-1-benzopyran-6-yl]ethan-1-one sulfuric acid 、 邻氯苯甲酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以78%的产率得到N-[(3S,4S)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydro-2H-1-benzopyran-4-yl]-2-chlorobenzamide
  参考文献：
  名称：

  [EN] PRODRUG COMPOUNDS
  [FR] COMPOSÉS DE TYPE PROMÉDICAMENT

  摘要：

  公式（Ia）或（Ib）的化合物，或其药学上可接受的盐，其中Q、R2、Ar、A和R1如权利要求1所定义。所述化合物是缝隙连接阻滞剂，可用于治疗或预防一系列疾病，包括偏头痛、癫痫、非癫痫性抽搐、脑损伤（包括中风、颅内出血和创伤引起的）、疼痛、神经退行性疾病或心血管疾病，包括心肌梗死、冠状动脉重建术或心绞痛。

  公开号：

  WO2015097461A1

文献信息

• Pharmaceutical composition containing bicyclic type compounds
  申请人：SmithKline Beecham p.l.c.

  公开号：US20010021780A1

  公开（公告）日：2001-09-13

  A compound of formula (I) or pharmaceutically acceptable salt thereof: 1 wherein: either Y is N and R 2 is hydrogen, or Y is C—R 1 where: either one of R 1 and R 2 is hydrogen and the other is selected from the class of hydrogen, C 3-8 cycloalkyl, C 1-6 alkyl optionally interrupted by oxygen or substituted by hydroxy, C 1-6 alkoxy or substituted aminocarbonyl, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, C 1-6 alkylcarbonyloxy, C 1-6 alkoxy, nitro, cyano, halo, trifluoromethyl, CF 3 S, or a group CF 3 —A—, where A is —CF 2 —, —CO—, —CH 2 —, CH(OH), SO 2 , SO, CH 2 —O, or CONH, or a group CF 2 H—A′-where A′ is oxygen, sulphur, SO, SO 2 , CF 2 , or CFH; trifluoromethoxy, C 1-6 alkylsulphinyl, perfluoro C 2-6 alkylsulphonyl, C 1-6 alkylsulphonyl, C 1-6 alkoxysulphinyl, C 1-6 alkoxysulphonyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, phosphono, arylcarbonyloxy, heteroarylcarbonyloxy, arylsulphinyl, heterarylsulphinyl, arylsulphonyl, heteroarylsulphonyl in which any aromatic moiety is optionally substituted, C 1-6 alkylcarbonylamino, C 1-6 alkoxycarbonylamino, C 1-6 alkyl-thiocarbonyl, C 1-6 alkoxy-thiocarbonyl, C 1-6 alkyl-thiocarbonyloxy, 1-mercapto C 2-7 alkyl, formyl, or aminosulphinyl, aminosulphonyl or aminocarbonyl, any amino moiety being optionally substituted by one or two C 1-6 alkyl groups, or C 1-6 alkylsulphinylamino, C 1-6 alkylsulphonylamino, C 1-6 alkoxysulphinylamino or C 1-6 alkoxysulphonylamino, or ethylenyl terminally substituted by C 1-6 alkylcarbonyl, nitro or cyano, or —C(C 1-6 alkyl)NOH or —C(C 1-6 alkyl)NNH 2 , or one of R 1 and R 2 is nitro, cyano or C 1-3 alkylcarbonyl and the other is methoxy or amino optionally substituted by one or two C 1-6 alkyl or by C 2-7 alkanoyl; or R 1 and R 2 together are —(CH 2 ) 4 — or —CH═CH—CH═CH—, or form an optionally substituted triazole or oxadiazole ring; one of R 3 and R 4 is hydrogen or C 1-4 alkyl and the other is C 1-4 alkyl, CF 3 or CH 2 X a where X a is fluoro, chloro, bromo, iodo, C 1-4 alkoxy, hydroxy, C 1-4 alkylcarbonyloxy, —S—C 1-4 alkyl, nitro, amino optionally substituted by one or two C 1-4 alkyl groups; cyano or C 1-4 alkoxycarbonyl or R 3 and R 4 together are C 2-5 polymethylene optionally substituted by C 1-4 alkyl; R 5 is C 1-6 alkylcarbonyloxy, benzoyloxy, ONO 2 , benzyloxy, phenyloxy or C 1-6 alkoxy and R 6 and R 9 are hydrogen or R 5 is hydroxy and R 6 is hydrogen or C 1-2 alkyl and R 9 is hydrogen; R 7 is heteroaryl or phenyl; both of which are optionally substituted one or more times independently with a group or atom selected from chloro, fluoro, bromo, iodo, nitro, amino optionally substituted once or twice by C 1-4 alkyl, cyano, azido, C 1-4 alkyl, C 1-4 alkoxy, trifluoromethoxy and trifluoromethyl; R 8 is hydrogen; C 1-6 alkyl, OR 9 or NHCOR 10 wherein R 9 is hydrogen, C 1-6 alkyl, formyl, C 1-6 alkanoyl, aroyl or aryl-C 1-6 alkyl and R 10 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, mono or di C 1-6 alkyl amino, amino, amino-C 1-6 alkyl, hydroxy-C 1-6 alkyl, halo-C 1-6 alkyl, C 1-6 acyloxy-C 1-6 alkyl, C 1-6 alkoxycarbonyl-C 1-6 -alkyl, aryl or heteroaryl; the R 8 —N—CO—R 7 group being cis to the R 5 group; and X is oxygen or NR 10 where R 10 is hydrogen or C 1-6 alkyl with the proviso that the compound is not racemic cis-4-benzoylamino-6-cyano-3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3-ol.

  式 (I) 的化合物或其药学上可接受的盐： 1 其中 Y 是 N 且 R 2 是氢，或 Y 是 C-R 1 其中 R 1 和 R 2 中的一个为氢，另一个选自氢、C 3-8 环烷基 1-6 烷基，可选择被氧打断或被羟基取代，C 1-6 烷氧基或取代的氨基羰基，C 1-6 烷羰基、C 1-6 烷氧羰基、C 1-6 烷基羰氧基，C 1-6 烷氧基、硝基、氰基、卤代、三氟甲基、CF 3 S，或一个基团 CF 3 -A-，其中 A 是-CF 2 -、-CO-、-CH 2 -、CH（OH）、SO 2 、SO、CH 2 -O，或 CONH，或一个基团 CF 2 H-A′-其中 A′为氧、硫、SO、SO 2 、CF 2 或 CFH；三氟甲氧基，C 1-6 烷基亚磺酰基、全氟 C 2-6 烷基磺酰基、C 1-6 烷基磺酰基，C 1-6 烷氧基亚磺酰基，C 1-6 烷氧基磺酰基、芳基、杂芳基、芳基羰基、杂芳基羰基、膦酰基、芳基羰酰氧基、杂芳基羰酰氧基、芳基亚砜基、杂芳基亚砜基、芳基磺酰基、杂芳基磺酰基（其中任何芳香族基团均被任选取代）、C. 1-6 烷基羰基氨基、C 1-6 烷氧羰基氨基、C 1-6 烷基硫代羰基，C 1-6 烷氧基硫代羰基，C 1-6 烷基硫代羰氧基，1-巯基 C 2-7 烷基、甲酰基或氨基亚磺酰基、氨基磺酰基或氨基羰基，其中任何氨基可选择被一个或两个 C 1-6 烷基或 C 1-6 烷基亚磺酰氨基、C 1-6 烷基磺酰氨基、C 1-6 烷氧基亚磺酰氨基或 C 1-6 烷氧基磺酰基氨基，或被 C 1-6 烷基羰基、硝基或氰基取代的乙烯基，或-C(C 1-6 烷基）NOH 或-C（C 1-6 烷基）NNH 2 或 R 1 和 R 2 是硝基、氰基或 C 1-3 烷基羰基，另一个是甲氧基或氨基，任选被一个或两个 C 1-6 烷基或 C 2-7 烷酰基取代；或 R 1 和 R 2 一起是-(CH 2 ) 4 - 或-CH═CH-CH═CH-，或形成任选取代的三唑或噁二唑环； R 3 和 R 4 是氢或 C 1-4 烷基，另一个是 C 1-4 烷基、CF 3 或 CH 2 X a 其中 X a 是氟、氯、溴、碘、C 1-4 烷氧基、羟基、C 1-4 烷基羰氧基、-S-C 1-4 烷基、硝基、被一个或两个 C 1-4 烷基；氰基或 C 1-4 烷氧羰基或 R 3 和 R 4 一起是 C 2-5 可选择被 C 1-4 烷基取代； R 5 是 C 1-6 烷基羰氧基、苯甲酰氧基、ONO 2 、苄氧基、苯氧基或 C 1-6 烷氧基和 R 6 和 R 9 为氢或 R 5 是羟基，R 6 是氢或 C 1-2 烷基，R 9 是氢； R 7 是杂芳基或苯基；二者均可任选被选自氯、氟、溴、碘、硝基的基团或原子一次或多次独立取代，这些基团或原子可任选被 C 1-4 烷基、氰基、叠氮基、C 1-4 烷基、C 1-4 烷氧基、三氟甲氧基和三氟甲基； R 8 是氢；C 1-6 烷基、OR 9 或 NHCOR 10 其中 R 9 是氢、C 1-6 烷基、甲酰基、C 1-6 烷酰基、芳基或芳基-C 1-6 烷基和 R 10 是氢、C 1-6 烷基 1-6 烷氧基、单或双 C 1-6 烷基氨基、氨基、氨基-C 1-6 烷基、羟基-C 1-6 烷基、卤代-C 1-6 烷基、C 1-6 酰氧基-C 1-6 烷基、C 1-6 烷氧基羰基-C 1-6 -烷基、芳基或杂芳基； R 8 -N-CO-R 7 基团与 R 5 基团的顺式； X 是氧或 NR 10 其中 R 10 是氢或 C 1-6 烷基，但该化合物不是外消旋顺式-4-苯甲酰基氨基-6-氰基-3,4-二氢-2,2-二甲基-2H-苯并[b]吡喃-3-醇。
• PHARMACEUTICAL COMPOSITION CONTAINING BICYCLIC TYPE COMPOUNDS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0673374A1

  公开（公告）日：1995-09-27
• PRODRUG COMPOUNDS
  申请人：Proximagen Limited

  公开号：EP3087062A1

  公开（公告）日：2016-11-02
• US5948811A
  申请人：——

  公开号：US5948811A

  公开（公告）日：1999-09-07
• [EN] PHARMACEUTICAL COMPOSITION CONTAINING BICYCLIC TYPE COMPOUNDS<br/>[FR] COMPOSITION PHARMACEUTIQUE CONTENANT DES COMPOSES DU TYPE BICYCLIQUE
  申请人：——

  公开号：WO1994013657A1

  公开（公告）日：1994-06-23

  [EN] A compound of formula (I) or pharmaceutically acceptable salt thereof wherein: either Y is N and R2 is hydrogen, or Y is C-R1 where: either one of R1 and R2 is hydrogen and the other is selected from the class of hydrogen, C3-8 cycloalkyl, C1-6 alkyl optionally interrupted by oxygen or substituted by hydroxy, C1-6 alkoxy or substituted aminocarbonyl, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkoxy, nitro, cyano, halo, trifluoromethyl, CF3S, or a group CF3-A-, where A is -CF2-, -CO-, -CH2-, CH(OH), SO2, SO, CH2-O, or CONH, or a group CF2H-A'- where A' is oxygen, sulphur, SO, SO2, CF2 or CFH; trifluoromethoxy, C1-6 alkylsulphinyl, perfluoro C2-6 alkylsulphonyl, C1-6 alkylsulphonyl, C1-6 alkoxysulphinyl, C1-6 alkoxysulphonyl, aryl, heteroaryl, arylcarbonyl, heteroarylcarbonyl, phosphono, arylcarbonyloxy, heteroarylcarbonyloxy, arylsulphinyl, heteroarylsulphinyl, arylsulphonyl, heteroarylsulphonyl in which any aromatic moiety is optionally substituted, C1-6 alkylcarbonylamino, C1-6 alkoxycarbonylamino, C1-6 alkyl-thiocarbonyl, C1-6 alkoxy-thiocarbonyl, C1-6 alkyl-thiocarbonyloxy, 1-mercapto C2-7 alkyl, formyl, or aminosulphinyl, aminosulphonyl or aminocarbonyl, any amino moiety being optionally substituted by one or two C1-6 alkyl groups, or C1-6 alkylsulphinylamino, C1-6 alkylsulphonylamino, C1-6 alkoxysulphinylamino or C1-6 alkoxysulphonylamino, or ethylenyl terminally substituted by C1-6 alkylcarbonyl, nitro or cyano, or -C(C1-6 alkyl)NOH or -C(C1-6 alkyl)NNH2, or one of R1 and R2 is nitro, cyano or C1-3 alkylcarbonyl and the other is methoxy or amino optionally substituted by one or two C1-6 alkyl or by C2-7 alkanoyl; or R1 and R2 together are -(CH2)4- or -CH CH-CH CH-, or form an optionally substituted triazole or oxadiazole ring; and X is oxygen or NR10 where R10 is hydrogen or C1-6 alkyl with the proviso that the compound is not racemic cis-4-benzoylamino-6-cyano-3,4-dihydro-2,2-dimethyl-2H-benzo[b]pyran-3-ol.
  [FR] L'invention se rapporte à un composé de la formule (I) ou à un sel pharmaceutiquement acceptable de celui-ci, dans laquelle soit Y représente N et R2 hydrogène, soit Y représente C-R1 où soit un chaînon de R1 et R2 représente hydrogène et l'autre chaînon est sélectionné à partir de la classe d'hydrogène, cycloalkyle C3-8, alkyle C1-6 éventuellement substitué interrompu par oxygène, ou substitué par hydroxy, alcoxy C1-6 ou aminocarbonyle substitué, alkylcarbonyle C1-6, alcoxycarbonyle C1-6, alkylcarbonyloxy C1-6, alcoxy C1-6, nitro, cyano, halo, trifluorométhyle, CF3S, ou un groupe CF3-A-, où A représente -CF2-, -CO-, -CH2-, CH(OH), SO2, SO, CH2-O, ou CONH, ou un groupe CF2H-A', où A' représente oxygène, soufre, SO, SO2, CF2 ou CFH; trifluorométhoxy, alkylsulphinyle C1-6, perfluoro C2-6 alkylsulphonyle, alkylsulphonyle C1-6, alcoxysulphinyle C1-6, alcoxysulphonyle C1-6, aryle, hétéroaryle, arylcarbonyle, hétéroarylcarbonyle,, phosphoro, arylcarbonyloxy, hétéroarylcarbonyloxy, arylsulphinyle, hétéroarylsuphinyle, arylsulphonyle, hétéroarylsulphonyle dans lequel toute fraction aromatique est éventuellement substituée, alkylecarbonylamino C1-6, alcoxycarbonylamino C1-6, alkyl-thiocarbonyle C1-6, alcoxythiocarbonyle C1-6, alkyl-thiocarbonyloxy C1-6, 1-mercapto C2-7 alkyle, formyle, ou aminosulphinyle, aminosulphonyle ou aminocarbonyle, toute fraction amino étant éventuellement substituée par un ou deux groupes alkyle C1-6, ou alkylsulphinylamino C1-6, alkylsulphonylamino C1-6, alcoxysulphinylamino C1-6 ou alcoxysulphonylamino C1-6, ou éthylène substitué en terminaison par alkylcarbonyle C1-6, nitro ou cyano, ou -C(C1-6alkyl)NOH ou -C(C1-6alkyl)NNH2, ou un chaînon de R1 et R2 représente nitro, cyano ou alkylcarbonyle C1-3 et l'autre chaînon représente méthoxy ou amino éventuellement substitué par un ou deux alkyle C1-6 ou par alcanoyle C2-7; ou R1 et R2 réunis représentent (CH2)4- ou -CH$(1,3)$CH-CH$(1,3)$CH-, ou forment un anneau d'oxadiazole ou triazole éventuellement substitué; et X représente oxygène ou NR10 où