(+)-7-Acetylamino-3,4-dihydro-3,4-epoxy-6-nitro-2,2-dimethyl-2H-1-benzopyran | 89316-80-3

• 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: (+)-7-Acetylamino-3,4-dihydro-3,4-epoxy-6-nitro-2,2-dimethyl-2H-1-benzopyran
• 英文别名: 7-Acetamido-3,4-dihydro-2,2-dimethyl-6-nitro-3,4-epoxy-2H-benzo-[b]pyran；7-Acetamido-3,4-epoxy-3,4-dihydro-2,2-dimethyl-6-nitro-2H-benzo[b]pyran；N-(2,2-dimethyl-6-nitro-1a,7b-dihydrooxireno[2,3-c]chromen-5-yl)acetamide
• CAS: 89316-80-3
• 化学式: C₁₃H₁₄N₂O₅
• 分子量: 278.265
• InChiKey: MFRYULPFXTWZOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  96.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+)-7-Acetylamino-3,4-dihydro-3,4-epoxy-6-nitro-2,2-dimethyl-2H-1-benzopyran 在 sodium hydroxide 、 氨 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 120.5h， 生成 N-((3R,4S)-7-Acetylamino-3-hydroxy-2,2-dimethyl-6-nitro-chroman-4-yl)-4-chloro-butyramide
  参考文献：
  名称：

  4-（环酰胺基）-2H-1-苯并吡喃的合成及降压活性。

  摘要：

  描述了口服给有意识的自发性高血压大鼠的一系列新型4-（环酰胺基）-2H-1-苯并吡喃-3-醇的合成和降压活性。内酰胺环大小，内酰胺环中杂原子的存在，在C（2）和C（3）处的取代，在C（3）和C（4）处的相对立体化学以及芳香族取代模式对血压降低的影响该系列的活性已经确定。这项工作的关键化合物2 [BRL 34915; （（+/-）-6-氰基-3,4-二氢-2,2-二甲基-反-4-（2-氧吡咯烷-1-基）-2H-1-苯并吡喃-3-醇]已经解决，发现降压活性主要存在于（-）对映体中。制备这类化合物的关键步骤是环酰胺阴离子对适当环氧化物的作用。另一种方法

  DOI：

  10.1021/jm00161a011

文献信息

• 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。
• Chroman-3-ol compounds
  申请人：Beecham Group p.l.c.

  公开号：US04644070A1

  公开（公告）日：1987-02-17

  Anti-hypertensive compounds of formula (I): ##STR1## wherein: 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.3-6 spiroalkyl; R.sub.5 is hydrogen, C.sub.1-3 alkyl or C.sub.1-8 acyl; and n is 1 or 2; the lactam group being trans to the OR.sub.5 group; or, when the other of R.sub.1 and R.sub.2 is amino, a pharmaceutically acceptable salt thereof.

  式(I)的降压化合物：##STR1## 其中：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，或者R.sub.3和R.sub.4与它们连接的碳原子一起是C.sub.3-6螺烷基；R.sub.5是氢、C.sub.1-3烷基或C.sub.1-8酰基；n为1或2；内酰胺基团与OR.sub.5基团相对；或者，当R.sub.1和R.sub.2中的另一个是氨基时，其药学上可接受的盐。
• 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.

  化合物的式子（I）：##STR1## 其中：R.sub.1和R.sub.2中的任意一个是氢，另一个选择自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烷基磺酰基，C.sub.1-6烷基磺酰基，C.sub.1-6烷氧基磺酰基，C.sub.1-6烷氧基磺酰基，C.sub.1-6烷基羰基氨基，C.sub.1-6烷氧基羰基氨基，C.sub.1-6硫代羰基烷基，C.sub.1-6硫代羰基烷氧基，C.sub.1-6烷基硫代羰基氧基，C.sub.1-6烷基硫代甲基，甲酰基或氨基磺酰基，氨基部分可以选择性地被一个或两个C.sub.1-6烷基取代，或C.sub.1-6烷基磺酰基氨基，C.sub.1-6烷基磺酰胺基C.sub.1-6烷氧基磺酰基氨基或C.sub.1-6烷氧基磺酰胺基或以C.sub.1-6烷基羰基，硝基或氰基末端取代的乙烯基，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，可以选择性地被一个或两个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与它们所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.6一起是一个键；R.sub.7是氢，C.sub.1-6烷基，可以选择性地被羟基，C.sub.1-6烷氧基，C.sub.1-6烷氧羰基或羧基取代，或由卤素取代的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.6一起不是键时，R.sub.8--N--CX--R.sub.7基团与R.sub.5基团是反式的；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。
• 4-Amino-benzo[b]pyran-3-ol derivatives
  申请人：Beecham Group p.l.c.

  公开号：US04542149A1

  公开（公告）日：1985-09-17

  Anti-hypertensive compounds of formula (I): ##STR1## wherein: 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.3-6 spiroalkyl; R.sub.5 is hydrogen, C.sub.1-3 alkyl or C.sub.1-8 acyl; and n is 1 or 2; the lactam group being trans to the OR.sub.5 group; or, when the other of R.sub.1 and R.sub.2 is amino, a pharmaceutically acceptable salt thereof.

  化合物（I）的降压化合物：##STR1## 其中：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，可以被一个或两个C.sub.1-6烷基或C.sub.2-7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，或者R.sub.3和R.sub.4与它们连接的碳原子一起是C.sub.3-6螺旋烷基; R.sub.5是氢，C.sub.1-3烷基或C.sub.1-8酰基; n为1或2; 内酰胺基在OR.sub.5基团的对面; 或者，当R.sub.1和R.sub.2中的另一个是氨基时，其药学上可接受的盐。
• Benzopyrans useful for treating hypertension
  申请人：Beecham Group p.l.c.

  公开号：US04568692A1

  公开（公告）日：1986-02-04

  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：##STR1## 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烷氧基羰基，C.sub.1-6烷基羰氧基，C.sub.1-6烷基羟甲基，硝基，氰基，氯代，三氟甲基，C.sub.1-6烷基亚磺酰基，C.sub.1-6烷基磺酰基，C.sub.1-6烷氧基亚磺酰基，C.sub.1-6烷氧基磺酰基，C.sub.1-6烷基羰基氨基，C.sub.1-6烷氧基羰基氨基，C.sub.1-6烷基硫代羰基，C.sub.1-6烷氧基硫代羰基，C.sub.1-6烷基硫代羰氧基，C.sub.1-6烷基硫甲基，甲酰基或氨基亚磺酰基，氨基磺酰基或氨基羰基，氨基基团可选择地被一个或两个C.sub.1-6烷基取代，或C.sub.1-6烷基亚磺酰氨基，C.sub.1-6烷基磺酰氨基，C.sub.1-6烷氧基亚磺酰氨基或C.sub.1-6烷氧基磺酰氨基或以C.sub.1-6烷基羰基，硝基或氰基为末端的乙烯基，或 -C（C.sub.1-6烷基）NOH或-C（C.sub.1-6烷基）NNH.sub.2中的一个为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.6一起是一个键; R.sub.7是氢，可选择地被羟基，C.sub.1-6烷氧基，C.sub.1-6烷氧基羰基或羧基取代的C.sub.1-6烷基，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.6一起不是键时，R.sub.8--N--CX--R.sub.7基团是与R.sub.5基团反向的; 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降压活性。