rac-5-[(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2yl)ethynyl]-2-hydroxybenzoic acid methyl ester

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: rac-5-[(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2yl)ethynyl]-2-hydroxybenzoic acid methyl ester
• 英文别名: rac-5-[(3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethynyl]-2-hydroxybenzoic acid methyl ester；methyl 2-hydroxy-5-[2-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)ethynyl]benzoate
• 化学式: C₂₃H₂₄O₅
• 分子量: 380.441
• InChiKey: CQJQKSIANGNMQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  rac-5-[(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2yl)ethynyl]-2-hydroxybenzoic acid methyl ester 在 钯 hexane-diethyl ether 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以to give 0.5 g of colorless crystals with m.p. 108°-110°的产率得到rac-5-[2-(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2-yl)ethyl]-2hydroxybenzoic acid methyl ester
  参考文献：
  名称：

  Chromanes and their pharmaceutical compositions and methods

  摘要：

  式子为##STR1##的消旋化合物，其中A为--C.tbd.C--R.sub.6，--CH.sub.2 --CH.sub.2 --R.sub.7或##STR2##，其余变量如说明书中所定义，以及它们的对映体和盐被描述。式I的化合物表现出5-脂氧合酶抑制剂的活性，并抑制脂质过氧化。因此，它们在治疗由过度氧化代谢通过5-脂氧合酶途径引起或加重的疾病以及治疗炎症、关节炎、过敏、哮喘和牛皮癣方面非常有用。式I的化合物也可用于防止脂质过氧化，从而保护脂质膜免受氧化应激的影响。

  公开号：

  US05260294A1
• 作为产物：
  描述：

  (S)-(+)2-ethynyl-3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyran-6-ol 、 5-碘水杨酸甲酯 在 silica gel 、 ethyl acetate n-hexane 作用下， 以 二氯甲烷 为溶剂， 以to yield colorless crystals with m.p. 151°-153° C.的产率得到rac-5-[(3,4-Dihydro-6-hydroxy-2,5,7,8-tetramethyl-2H-1-benzopyran-2yl)ethynyl]-2-hydroxybenzoic acid methyl ester
  参考文献：
  名称：

  Chromanes and their pharmaceutical compositions and methods

  摘要：

  式子为##STR1##的消旋化合物，其中A为--C.tbd.C--R.sub.6，--CH.sub.2 --CH.sub.2 --R.sub.7或##STR2##，其余变量如说明书中所定义，以及它们的对映体和盐被描述。式I的化合物表现出5-脂氧合酶抑制剂的活性，并抑制脂质过氧化。因此，它们在治疗由过度氧化代谢通过5-脂氧合酶途径引起或加重的疾病以及治疗炎症、关节炎、过敏、哮喘和牛皮癣方面非常有用。式I的化合物也可用于防止脂质过氧化，从而保护脂质膜免受氧化应激的影响。

  公开号：

  US05260294A1

文献信息

• Pharmacologically active chromanes
  申请人：Hoffmann-La Roche Inc.

  公开号：US05132310A1

  公开（公告）日：1992-07-21

  Racemic Compounds of the formula ##STR1## A is --C.tbd.C--R.sub.6, --CH.sub.2 --CH.sub.2 --R.sub.7 or ##STR2## R.sub.1 is hydrogen or lower alkanoyl, R.sub.2, R.sub.3, and R.sub.4 independently are hydrogen or lower alkyl, R.sub.5 is lower alkyl, R.sub.6 is a heteroaromatic radical or an aromatic radical selected from phenyl, naphthyl or phenanthryl, which aromatic radical may optionally be substituted by one or more substituents selected from chlorine, fluorine, lower alkyl, lower alkoxy, phenyl lower alkoxy, lower alkanoyl, lower alkanoyloxy, hydroxy-lower alkyl, carboxy, lower alkoxycarbonyl, hydroxyimino lower alkyl, amino, amino lower alkyl, mono- or di-lower alkylamino, mono- or di-lower alkylamino-lower alkyl, lower alkanoylamino, aminocarbonyl, lower alkylaminocarbonyl, lower dialkylaminocarbonyl, trifluoroacetylamino, trifluoromethyl, hydroxy, pyridyl, or on adjacent carbons can be ##STR3## wherein R' is hydrogen, lower alkanoyl, trifluoroacetyl and R" hydrogen or lower alkyl, R.sub.7 is a heteroaromatic radical or an aromatic radical selected from phenyl, naphthyl or phenanthryl, which aromatic radical may optionally be substituted by one or more substituents selected from chlorine, fluorine, lower alkyl, lower alkoxy, phenyl-lower alkoxy of 2-7 carbon atoms, lower alkanoyl, lower alkanoyloxy, hydroxy-lower alkyl, carboxy, lower alkoxycarbonyl, amino, amino-lower alkyl, mono- or di-lower alkylamino, mono- or di-lower alkylamino-lower alkyl, lower alkanoylamino, aminocarbonyl, lower alkylaminocarbonyl, lower dialkylaminocarbonyl, trifluoroacetylamino, trifluoromethyl, hydroxy or pyridyl, or on adjacent carbons can be ##STR4## wherein R' is hydrogen, lower alkanoyl, trifluoroacetyl and R" hydrogen or lower alkyl, R.sub.8, R.sub.9, and R.sub.10, independently, are hydrogen, hydroxy, lower alkyl, lower alkoxy, hydroxy lower alkyl, fluorine, chlorine or lower alkanoyl provided that no more than one of R.sub.8, R.sub.9, and R.sub.10 is hydroxy, lower alkoxy, lower hydroxyalkyl, fluorine, chlorine or lower alkanoyl, and Y is CH or N, and their enantiomer and salts thereof are described. The compounds of formula I exhibit activity as inhibitors of 5-lipoxygenase and inhibit lipid peroxidation. They are, therefore, useful in the treatment of diseases caused or aggravated by excess oxidative metabolism of arachidonic acid via the 5-lipoxygenase pathway and in the treatment of inflammation, arthritis, allergies, asthma and psoriasis. The compounds of formula I can also be used to prevent peroxidation of lipids and thus protect lipid membranes from oxidative stress.

  式为##STR1##的外消旋化合物，其中A为--C.tbd.C--R.sub.6，--CH.sub.2--CH.sub.2--R.sub.7或##STR2##R.sub.1为氢或低烷酰基，R.sub.2、R.sub.3和R.sub.4独立地为氢或低烷基，R.sub.5为低烷基，R.sub.6为杂环芳基或苯基、萘基或菲基中选择的芳基，该芳基可以选择地由一个或多个取代基选自氯、氟、低烷基、低烷氧基、苯基低烷氧基、低烷酰基、低烷酰氧基、羟基-低烷基、羧基、低烷氧羰基、羟基亚胺-低烷基、氨基、氨基低烷基、单或二低烷基氨基、单或二低烷基氨基-低烷基、低烷酰氨基、氨基羰基、低烷基氨基羰基、低二烷基氨基羰基、三氟乙酰氨基、三氟甲基、羟基、吡啶基或相邻碳上可以为##STR3##，其中R'为氢、低烷酰基、三氟乙酰基，R"为氢或低烷基，R.sub.7为杂环芳基或苯基、萘基或菲基中选择的芳基，该芳基可以选择地由一个或多个取代基选自氯、氟、低烷基、低烷氧基、2-7个碳原子的苯基-低烷氧基、低烷酰基、低烷酰氧基、羟基-低烷基、羧基、低烷氧羰基、氨基、氨基低烷基、单或二低烷基氨基、单或二低烷基氨基-低烷基、低烷酰氨基、氨基羰基、低烷基氨基羰基、低二烷基氨基羰基、三氟乙酰氨基、三氟甲基、羟基或吡啶基，或相邻碳上可以为##STR4##，其中R'为氢、低烷酰基、三氟乙酰基，R"为氢或低烷基，R.sub.8、R.sub.9和R.sub.10独立地为氢、羟基、低烷基、低烷氧基、羟基低烷基、氟、氯或低烷酰基，前提是R.sub.8、R.sub.9和R.sub.10中最多只有一个为羟基、低烷氧基、低羟基烷基、氟、氯或低烷酰基，Y为CH或N，它们的对映体和盐被描述。公式I的化合物表现为5-脂氧合酶的抑制剂和抑制脂质过氧化。因此，它们在治疗由过量的通过5-脂氧合酶途径的花生四烯酸氧化代谢引起或加重的疾病以及治疗炎症、关节炎、过敏、哮喘和牛皮癣方面是有用的。公式I的化合物也可以用于预防脂质过氧化，从而保护脂质膜免受氧化应激的影响。
• US5015661A
  申请人：——

  公开号：US5015661A

  公开（公告）日：1991-05-14
• US5132310A
  申请人：——

  公开号：US5132310A

  公开（公告）日：1992-07-21
• US5260294A
  申请人：——

  公开号：US5260294A

  公开（公告）日：1993-11-09
• Chromanes and their pharmaceutical compositions and methods
  申请人：Hoffmann-La Roche Inc.

  公开号：US05015661A1

  公开（公告）日：1991-05-14

  Racemic Compounds of the formula ##STR1## A is --C.tbd.C--R.sub.6, --CH.sub.2 --CH.sub.2 --R.sub.7 or ##STR2## R.sub.1 is hydrogen or lower alkanoyl, R.sub.2, R.sub.3, and R.sub.4 independently are hydrogen or lower alkyl, R.sub.5 is lower alkyl, R.sub.6 is a heteroaromatic radical or an aromatic radical selected from phenyl, naphthyl or phenanthryl, which aromatic radical may optionally be substituted by one or more substituents selected from chlorine, fluorine, lower alkyl, lower alkoxy, phenyl lower alkoxy, lower alkanoyl, lower alkanoyloxy, hydroxy-lower alkyl, carboxy, lower alkoxycarbonyl, hydroxyimino lower alkyl, amino, amino lower alkyl, mono- or di-lower alkylamino, mono- or di-lower alkylamino-lower alkyl, lower alkanoylamino, aminocarbonyl, lower alkylaminocarbonyl, lower dialkylaminocarbonyl, trifluoroacetylamino, trifluoromethyl, hydroxy, pyridyl, or on adjacent carbons can be ##STR3## wherein R' is hydrogen, lower alkanoyl, trifluoroacetyl and R" hydrogen or lower alkyl, R.sub.7 is a heteroaromatic radical or an aromatic radical selected from phenyl, naphthyl or phenanthryl, which aromatic radical may optionally be substituted by one or more substituents selected from chlorine, fluorine, lower alkyl, lower alkoxy, phenyl-lower alkoxy of 2-7 carbon atoms, lower alkanoyl, lower alkanoyloxy, hydroxy-lower alkyl, carboxy, lower alkoxycarbonyl, amino, amino-lower alkyl, mono- or di-lower alkylamino, mono- or di-lower alkylamino-lower alkyl, lower alkanoylamino, aminocarbonyl, lower alkylaminocarbonyl, lower dialkylaminocarbonyl, trifluoroacetylamino, trifluoromethyl, hydroxy or pyridyl, or on adjacent carbons can be ##STR4## wherein R' is hydrogen, lower alkanoyl, trifluoroacetyl and R" hydrogen or lower alkyl, R.sub.8, R.sub.9, R.sub.10, independently, are hydrogen, hydroxy, lower alkyl, lower alkoxy, hydroxy lower alkyl, fluorine, chlorine or lower alkanoyl provided that no more than one of R.sub.8, R.sub.9, and R.sub.10 is hydroxy, lower alkoxy, lower hydroxyalkyl, fluorine, chlorine or lower alkanoyl, and Y is CH or N, and their enantiomer and salts thereof are described. The compounds of formula I exhibit activity as inhibitors of 5-lipoxygenase and inhibit lipid peroxidation. They are, therefore, useful in the treatment of diseases caused or aggravated by excess oxidative metabolism of arachidonic acid via the 5-lipoxygenase pathway and in the treatment of inflammation, arthritis, allergies, asthma and psoriasis. The compounds of formula I can also be used to prevent peroxidation of lipids and thus protect lipid membranes from oxidative stress.

  公式为##STR1##的消旋化合物。其中A为--C.tbd.C--R.sub.6，--CH.sub.2 --CH.sub.2 --R.sub.7或##STR2##，R.sub.1为氢或较低的烷酰基，R.sub.2、R.sub.3和R.sub.4独立地为氢或较低的烷基，R.sub.5为较低的烷基，R.sub.6为异芳基或苯基，萘基或苯并芘基中选择的芳基，该芳基可以选择性地被氯、氟、较低烷基、较低烷氧基、苯基较低烷氧基、较低烷酰基、较低烷酰氧基、羟基较低烷基、羧基、较低烷氧羰基、羟基亚胺较低烷基、氨基、氨基较低烷基、单烷基氨基或二烷基氨基、单烷基氨基或二烷基氨基较低烷基、较低烷酰胺基、氨基羰基、较低烷基氨基羰基、较低二烷基氨基羰基、三氟乙酰氨基、三氟甲基、羟基、吡啶基或相邻碳上的可以是##STR3##，其中R'为氢、较低烷酰基、三氟乙酰基，R"为氢或较低烷基，R.sub.7为异芳基或苯基，选择自苯基、萘基或苯并芘基的芳基，该芳基可以选择性地被氯、氟、较低烷基、较低烷氧基、苯基较低烷氧基（碳原子数为2-7）、较低烷酰基、较低烷酰氧基、羟基较低烷基、羧基、较低烷氧羰基、氨基、氨基较低烷基、单烷基氨基或二烷基氨基、单烷基氨基或二烷基氨基较低烷基、较低烷酰胺基、氨基羰基、较低烷基氨基羰基、较低二烷基氨基羰基、三氟乙酰氨基、三氟甲基、羟基或吡啶基，或相邻碳上的可以是##STR4##，其中R'为氢、较低烷酰基、三氟乙酰基，R"为氢或较低烷基，R.sub.8、R.sub.9、R.sub.10独立地为氢、羟基、较低烷基、较低烷氧基、羟基较低烷基、氟、氯或较低烷酰基，但R.sub.8、R.sub.9和R.sub.10中不超过一个为羟基、较低烷氧基、较低羟基烷基、氟、氯或较低烷酰基，Y为CH或N，描述了它们的对映体和盐。公式I的化合物表现出作为5-脂氧酶抑制剂的活性，并抑制脂质过氧化。因此，它们在治疗由于花生四烯酸通过5-脂氧酶途径的过度氧化代谢引起或加重的疾病以及治疗炎症、关节炎、过敏、哮喘和牛皮癣方面是有用的。公式I的化合物还可用于预防脂质过氧化，从而保护脂质膜免受氧化应激的影响。