N-((3R,4S)-6-Acetyl-3-hydroxy-2,2-dimethyl-chroman-4-yl)-acetamide | 128360-19-0

• 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-((3R,4S)-6-Acetyl-3-hydroxy-2,2-dimethyl-chroman-4-yl)-acetamide
• 英文别名: N-[(3R,4S)-6-acetyl-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]acetamide
• CAS: 128360-19-0
• 化学式: C₁₅H₁₉NO₄
• 分子量: 277.32
• InChiKey: FBINZVGXSZQPIL-UONOGXRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  6-Acetyl-3,4-dihydro-2,2-dimethyl-3,4-epoxy-2H-benzo[b]pyran 在 氨 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-((3R,4S)-6-Acetyl-3-hydroxy-2,2-dimethyl-chroman-4-yl)-acetamide
  参考文献：
  名称：

  4-（取代-羰基氨基）-2H-1-苯并吡喃的合成及降压活性。

  摘要：

  描述了口服给予有意识的自发性高血压大鼠的一系列新型4-（取代-羰基氨基）-2H-1-苯并吡喃-3-醇的合成和降压活性。对于具有在羰基侧翼的烷基，氨基或芳基的化合物，观察到最佳活性。在烷基和氨基系列中，最有效的化合物分别包含甲基和甲基氨基。已使用-86作为标记物，将几种类似物与cromakalim（1）对兔肠系膜动脉钾离子外流的作用进行了比较。每种化合物增强rub 86流出的能力与其降血压活性大致平行​​，因此这些类似物（如化合物（1））属于已归类为钾通道激活剂的一系列药物。

  DOI：

  10.1021/jm00171a051

文献信息

• 4-Acylaminobenzopyrans useful as anti-hypertensive agents
  申请人：Beecham Group p.l.c.

  公开号：US04481214A1

  公开（公告）日：1984-11-06

  Compounds of formula (I): ##STR1## wherein: either one of R.sub.1 and R.sub.2 is hydrogen and the other is selected from the class of C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxycarbonyl, C.sub.1-6 alkylcarbonyloxy, C.sub.1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C.sub.1-6 alkylsulphinyl, C.sub.1-6 alkylsulphonyl, C.sub.1-6 alkoxysulphinyl, C.sub.1-6 alkoxysulphonyl, C.sub.1-6 alkylcarbonylamino, C.sub.1-6 alkoxycarbonylamino, C.sub.1-6 alkyl-thiocarbonyl, C.sub.1-6 alkoxy-thiocarbonyl, C.sub.1-6 alkyl-thiocarbonyloxy, C.sub.1-6 alkyl-thiolmethyl, formyl or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C.sub.1-6 alkyl groups, or C.sub.1-6 alkylsulphinylamino, C.sub.1-6 alkylsulphonylamino C.sub.1-6 alkoxysulphinylamino or C.sub.1-6 alkoxysulphonylamino or ethylenyl terminally substituted by C.sub.1-6 alkylcarbonyl, nitro or cyano, or --C(C.sub.1-6 alkyl)NOH or --C(C.sub.1-6 alkyl)NNH.sub.2, or one of R.sub.1 and R.sub.2 is nitro, cyano or C.sub.1-3 alkylcarbonyl and the other is methoxy or amino optionally substituted by one or two C.sub.1-6 alkyl or by C.sub.2-7 alkanoyl; one of R.sub.3 and R.sub.4 is hydrogen or C.sub.1-4 alkyl and the other is C.sub.1-4 alkyl or R.sub.3 and R.sub.4 together with the carbon atom to which they are attached are C.sub.2-5 polymethylene; either R.sub.5 is hydroxy, C.sub.1-6 alkoxy or C.sub.2-7 acyloxy and R.sub.6 is hydrogen or R.sub.5 and R.sub.6 together are a bond; R.sub.7 is hydrogen, C.sub.1-6 alkyl optionally substituted by hydroxy, C.sub.1-6 alkoxy, C.sub.1-6 alkoxycarbonyl or carboxy, or C.sub.1-2 alkyl substituted by halogen, or C.sub.2-6 alkenyl; R.sub.8 is hydrogen or C.sub.1-6 alkyl; and X is oxygen or sulphur; the R.sub.8 --N--CX--R.sub.7 group being trans to the R.sub.5 group when R.sub.5 and R.sub.6 together are not a bond; or, when one or the other of R.sub.1 and R.sub.2 is an amino or an amino-containing group, a pharmaceutically acceptable salt thereof, having anti-hypertensive activity.

  式（I）的化合物：其中：R.sub.1和R.sub.2中的任意一个是氢，另一个选自C.sub.1-6烷基羰基，C.sub.1-6烷氧羰基，C.sub.1-6烷基羰氧基，C.sub.1-6烷基羟甲基，硝基，氰基，氯基，三氟甲基，C.sub.1-6烷基砜基，C.sub.1-6烷基磺酰基，C.sub.1-6烷氧基砜基，C.sub.1-6烷氧基磺酰基，C.sub.1-6烷基羰基氨基，C.sub.1-6烷氧羰基氨基，C.sub.1-6硫代烷基羰基，C.sub.1-6硫代烷氧基羰基，C.sub.1-6硫代烷基羰氧基，C.sub.1-6硫代烷硫基甲基，甲酰基或氨基砜基，氨基磺酰基或氨基羰基，氨基部分可选择地被一个或两个C.sub.1-6烷基基团取代，或C.sub.1-6烷基砜基氨基，C.sub.1-6烷基磺酰基氨基，C.sub.1-6烷氧基砜基氨基或C.sub.1-6烷氧基磺酰基氨基，或末端被C.sub.1-6烷基羰基，硝基或氰基取代的乙烯基，或--C(C.sub.1-6烷基)NOH或--C(C.sub.1-6烷基)NNH.sub.2，或R.sub.1和R.sub.2中的一个是硝基，氰基或C.sub.1-3烷基羰基，另一个是甲氧基或氨基，可选择地被一个或两个C.sub.1-6烷基或C.sub.2-7烷酰基取代；R.sub.3和R.sub.4中的一个是氢或C.sub.1-4烷基，另一个是C.sub.1-4烷基或R.sub.3和R.sub.4与它们连接的碳原子一起是C.sub.2-5聚亚甲基；R.sub.5是羟基，C.sub.1-6烷氧基或C.sub.2-7酰氧基，R.sub.6是氢或R.sub.5和R.sub.6一起是键合；R.sub.7是氢，C.sub.1-6烷基，可选择地被羟基，C.sub.1-6烷氧基，C.sub.1-6烷氧羰基或羧基取代，或被卤素取代的C.sub.1-2烷基，或C.sub.2-6烯基；R.sub.8是氢或C.sub.1-6烷基；X是氧或硫；当R.sub.5和R.sub.6一起不是键合时，R.sub.8--N--CX--R.sub.7基与R.sub.5基是反式的；或者，当R.sub.1和R.sub.2中的一个是氨基或含氨基的基团时，其药学上可接受的盐，具有抗高血压活性。
• Pharmaceutically active aminobenzopyrans
  申请人：BEECHAM GROUP PLC

  公开号：EP0095316A1

  公开（公告）日：1983-11-30

  Compounds of formula (I): wherein: either one of R, and R2 is hydrogen and the other is selected from the class of C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonyloxy, C1-6 alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C1-6 alkylsulphinyl, C1-6 alkylsulphonyl, C1-6 alkoxysulphinyl, C1-6 alkoxysulphonyl, C1-6 alkylcarbonylamino, C1-6 alkoxycarbonylamino, C1-6 alkyl- thiocarbonyl, C1-6 alkoxy-thiocarbonyl, C1-6 alkyl- thiocarbonyloxy, C1-6 alkyl-thiolmethyl, formyl or aminosulphinyl, aminosulphonyl or aminocarbonyl, the 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 R, 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; one of R3 and R4 is hydrogen or C1-4 alkyl and the other is C1-4 alkyl or R3 and R4 together with the carbon atom to which they are attached are C2-5 polymethylene; either Rs is hydroxy, C1-6 alkoxy or C2-7 acyloxy and R6 is hydrogen or R5 and R6 together are a bond; R7 is hydrogen, C1-6 alkyl optionally substituted by hydroxy, C1-6 alkoxy, C1-6 alkoxycarbonyl or carboxy, or C1-2 alkyl substituted by halogen, or C2.6 alkenyl; R8 is hydrogen or C1-6 alkyl; and X is oxygen or sulphur; the Re-N-CX-R7 group being trans to the R5 group when R5 and R6 together are not a bond; or, when one or the other of R, and R2 is an amino or an amino-containing group, a pharmaceutically acceptable salt thereof, having anti-hypertensive activity.

  式(I)化合物： 其中 R 和 R2 中的任一个是氢，另一个选自 C1-6 烷基羰基、C1-6 烷氧基羰基、C1-6 烷基羰氧基、C1-6 烷基羟甲基、硝基、氰基、氯基、三氟甲基、C1-6 烷基亚磺酰基、C1-6 烷基磺酰基、C1-6 烷氧基磺酰基、C1-6 烷基羰基、C1-6 烷氧基磺酰基、C1-6 烷基羰基C1-6烷基磺酰基、C1-6烷氧基磺酰基、C1-6烷氧基磺酰基、C1-6烷基羰基氨基、C1-6烷氧基羰基氨基、C1-6烷基硫代羰基、C1-6烷氧基硫代羰基、C1-6烷基硫代羰氧基、C1-6烷基硫醇甲基、甲酰基或氨基磺酰基、氨基磺酰基或氨基羰基，氨基可选择被一个或两个 C1-6 烷基取代，或 C1-6 烷基亚磺酰氨基、C1-6 烷基磺酰基氨基、C1-6 烷氧基亚磺酰基氨基或 C1-6 烷氧基磺酰基氨基或乙烯基最终被 C1-6 烷基羰基取代、硝基或氰基，或-C(C1-6 烷基)NOH 或-C(C1-6 烷基)NNH2，或 R 和 R2 中的一个是硝基、氰基或 C1-3 烷基羰基，另一个是甲氧基或被一个或两个 C1-6 烷基或 C2-7 烷酰基任选取代的氨基； R3 和 R4 中的一个是氢或 C1-4 烷基，另一个是 C1-4 烷基，或者 R3 和 R4 连同它们所连接的碳原子是 C2-5 聚亚甲基； Rs 为羟基、C1-6 烷氧基或 C2-7 乙酰氧基，R6 为氢，或 R5 和 R6 合在一起为键； R7 是氢、任选被羟基、C1-6 烷氧基、C1-6 烷氧羰基或羧基取代的 C1-6 烷基，或被卤素取代的 C1-2 烷基，或 C2.6 烯基； R8 是氢或 C1-6 烷基；以及 X是氧或硫；当R5和R6合在一起不是键时，Re-N-CX-R7基团反式为R5基团；或者，当R和R2中的一个或另一个是氨基或含氨基的基团时，其为药学上可接受的盐，具有抗高血压活性。
• US4481214A
  申请人：——

  公开号：US4481214A

  公开（公告）日：1984-11-06
• US4568692A
  申请人：——

  公开号：US4568692A

  公开（公告）日：1986-02-04
• Synthesis and antihypertensive activity of 4-(substituted-carbonylamino)-2H-1-benzopyrans
  作者：Valerie A. Ashwood、Frederick Cassidy、Martin C. Coldwell、John M. Evans、Thomas C. Hamilton、David R. Howlett、Duncan M. Smith、Geoffrey Stemp

  DOI：10.1021/jm00171a051

  日期：1990.9

  The synthesis and antihypertensive activity of a series of novel 4-(substituted-carbonylamino)-2H-1-benzopyran-3-ols, administered orally to conscious spontaneously hypertensive rats, are described. Optimum activity was observed for compounds with alkyl, amino, or aryl groups flanking the carbonyl group. Of the alkyl and amino series the most potent compounds contained the methyl and methylamino groups

  描述了口服给予有意识的自发性高血压大鼠的一系列新型4-（取代-羰基氨基）-2H-1-苯并吡喃-3-醇的合成和降压活性。对于具有在羰基侧翼的烷基，氨基或芳基的化合物，观察到最佳活性。在烷基和氨基系列中，最有效的化合物分别包含甲基和甲基氨基。已使用-86作为标记物，将几种类似物与cromakalim（1）对兔肠系膜动脉钾离子外流的作用进行了比较。每种化合物增强rub 86流出的能力与其降血压活性大致平行​​，因此这些类似物（如化合物（1））属于已归类为钾通道激活剂的一系列药物。