3,4-dihydro-6-hydroxy-N',N',2,5,7,8-hexamethyl-2H-1-benzopyran-2-carboxhydrazide

• 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: 3,4-dihydro-6-hydroxy-N',N',2,5,7,8-hexamethyl-2H-1-benzopyran-2-carboxhydrazide
• 英文别名: 6-hydroxy-N',N',2,5,7,8-hexamethyl-3,4-dihydrochromene-2-carbohydrazide
• 化学式: C₁₆H₂₄N₂O₃
• 分子量: 292.378
• InChiKey: LDRCMLNYKZFYFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  对甲苯磺酸甲酯 、 3,4-dihydro-6-hydroxy-N',N',2,5,7,8-hexamethyl-2H-1-benzopyran-2-carboxhydrazide 在 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 3.0h， 生成 [(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)carbonyl]-1,1,1-trimethylhydrazinium, inner salt
  参考文献：
  名称：

  Cardioselective Ammonium, Phosphonium, and Sulfonium Analogs of .alpha.-Tocopherol and Ascorbic Acid That Inhibit in Vitro and ex Vivo Lipid Peroxidation and Scavenge Superoxide Radicals

  摘要：

  Analogues of alpha-tocopherol and ascorbic acid with permanently cationic substituents, i.e., phosphonium (8, 9), sulfonium (11), acylhydrazinium (13, 14), and ammonium (1, 16, 21), were synthesized, and the 2R and 2S enantiomers of the alpha-tocopherol analogues 1, 8, 11, and 13 were separated. The compounds were found to scavenge lipoperoxyl and superoxide radicals in vitro and accumulate in heart tissue (cardioselectivity) as demonstrated by measurement of ex vivo inhibition of lipid peroxidation in mouse heart homogenates and confirmed by HPLC determination of drug concentrations for 1 and 11. The 2R and 2S enantiomers of 1 inhibited ex vivo lipid peroxidation to an equal extent. Thus the in vivo uptake into myocytes (cardioselectivity) is independent of the geometry at the chiral center and common to permanently cationic compounds.

  DOI：

  10.1021/jm00015a010
• 作为产物：
  描述：

  奎诺二甲基丙烯酸酯 、 偏二甲肼 在 氯甲酸乙酯 、 三乙胺 作用下， 生成 3,4-dihydro-6-hydroxy-N',N',2,5,7,8-hexamethyl-2H-1-benzopyran-2-carboxhydrazide
  参考文献：
  名称：

  Cardioselective Ammonium, Phosphonium, and Sulfonium Analogs of .alpha.-Tocopherol and Ascorbic Acid That Inhibit in Vitro and ex Vivo Lipid Peroxidation and Scavenge Superoxide Radicals

  摘要：

  Analogues of alpha-tocopherol and ascorbic acid with permanently cationic substituents, i.e., phosphonium (8, 9), sulfonium (11), acylhydrazinium (13, 14), and ammonium (1, 16, 21), were synthesized, and the 2R and 2S enantiomers of the alpha-tocopherol analogues 1, 8, 11, and 13 were separated. The compounds were found to scavenge lipoperoxyl and superoxide radicals in vitro and accumulate in heart tissue (cardioselectivity) as demonstrated by measurement of ex vivo inhibition of lipid peroxidation in mouse heart homogenates and confirmed by HPLC determination of drug concentrations for 1 and 11. The 2R and 2S enantiomers of 1 inhibited ex vivo lipid peroxidation to an equal extent. Thus the in vivo uptake into myocytes (cardioselectivity) is independent of the geometry at the chiral center and common to permanently cationic compounds.

  DOI：

  10.1021/jm00015a010

文献信息

• Hydrazide derivatives of 3,4-dihydro-2H-1-benzopyrans
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05545660A1

  公开（公告）日：1996-08-13

  This invention relates to novel hydrazide acyl hydrazinium derivatives of certain 3,4-dihydro-2H-1-benzopyrans of the formula ##STR1## the stereoisomers and mixtures thereof, their inner salts, and the pharmaceutically acceptable salts thereof wherein R is H or C.sub.1-6 alkyl, R.sub.1 is C.sub.1-6 alkyl, R.sub.2 is H or --C(O)R,R.sub.3 and R.sub.4 are independently C.sub.1-6 alkyl; R.sub.5 is C.sub.1-6 alkyl, or ##STR2## with R.sub.8 being H or halogeno, n is zero, 1, 2, or 3 and is a halide, --S(O).sub.3 R.sub.6, or nothing when the inner salt is formed R.sub.6 is H, C.sub.1-6 alkyl, phenyl or 4-methylphenyl, to the intermediates, processes and techniques for their preparation, to their ability to manifest the property of being free radical scavengers, and to their end-use application in the treatment of disease conditions capable of being ameliorated by free radical scavengers.

  这项发明涉及某些3,4-二氢-2H-1-苯并吡喃的新型肼酰肼盐衍生物，其化学式为##STR1## 其立体异构体及其混合物，它们的内盐，及其药学上可接受的盐，其中R为H或C.sub.1-6烷基，R.sub.1为C.sub.1-6烷基，R.sub.2为H或--C(O)R，R.sub.3和R.sub.4独立地为C.sub.1-6烷基；R.sub.5为C.sub.1-6烷基，或##STR2## 其中R.sub.8为H或卤素，n为零，1，2或3且为卤化物，--S(O).sub.3R.sub.6，或当形成内盐时为空，R.sub.6为H，C.sub.1-6烷基，苯基或4-甲基苯基，以及它们的中间体，制备它们的方法和技术，它们表现为自由基清除剂的性质，以及它们在治疗能够通过自由基清除剂改善的疾病状况中的最终应用。
• HYDRAZIDE DERIVATIVES OF 3,4-DIHYDRO-2H-1-BENZOPYRANS
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0635011B1

  公开（公告）日：1996-12-18
• US5545660A
  申请人：——

  公开号：US5545660A

  公开（公告）日：1996-08-13
• [EN] HYDRAZIDE DERIVATIVES OF 3,4-DIHYDRO-2H-1-BENZOPYRANS<br/>[FR] DERIVES D'HYDRAZIDE DE 3,4-DYHYDRO-2H-1-BENZOPYRANNES
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：WO1993020059A1

  公开（公告）日：1993-10-14

  (EN) This invention relates to novel hydrazide acyl hydrazinium derivatives of certain 3,4-dihydro-2H-1-benzopyrans of formula (1), the stereoisomers and mixtures thereof, their inner salts, and the pharmaceutically acceptable salts thereof wherein R is H or C1-6 alkyl, R1 is C1-6 alkyl, R2 is H or -C(O)R, R3 and R4 are independently C1-6 alkyl; R5 is C1-6 alkyl, or (a) with R8 being H or halogeno, n is zero, 1, 2, or 3 and X is a halide, -S(O)3R6, or nothing when the inner salt is formed, R6 is H, C1-6 alkyl, phenyl or 4-methylphenyl, to the intermediates, processes and techniques for their preparation, to their ability to manifest the property of being free radical scavengers, and to their end-use application in the treatment of disease conditions capable of being ameliorated by free radical scavengers.(FR) L'invention se rapporte à de nouveaux dérivés d'hydrazinium acyle d'hydrazide de certains 3,4-dyhydro-2H-1-benzopyrannes représentés par la formule (1), à leur stéréoisomères et à leur mélanges, à leur sels intérieurs, ainsi qu'à leurs sels acceptables pharmaceutiquement, dans laquelle R représente H ou C1-6 alkyle, R1 représente C1-6 alkyle, R2 représente H ou -C(O)R, R3 et R4 représente indépendamment C1-6 alkyle; R5 représente C1-6 alkyle ou la formule (a) dans laquelle R8 représente H ou halogeno, n est zéro, 1, 2, 3 et X représente un halogénure, -S(O)3R6 ou rien quand le sel intérieur est constitué, R6 représente H, C1-6 alkyle, phényle ou 4-méthylphényle. L'invention se rapporte également aux intermédiaires, aux procédés et aux techniques servant à leur préparation, ainsi qu'à leur capacité d'agir en tant que piégeurs de radicaux libres et à leur application finale dans le traitement d'états pathologiques pouvant s'améliorer au moyen de l'utilisation de piégeurs de radicaux libres.