(S)-(+)2-ethynyl-3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyran-6-ol | 125133-62-2

• 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: (S)-(+)2-ethynyl-3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyran-6-ol
• 英文别名: 2-ethynyl-3,4-dihydro-2,5,7,8-tetramethyl-2H-6-benzopyranol；rac-3,4-dihydro-2-ethynyl-2,5,7,8-tetramethyl-2H-1-benzopyran-6ol；2-Ethynyl-2,5,7,8-tetramethyl-chroman-6-ol；2-ethynyl-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-ol
• CAS: 125133-62-2
• 化学式: C₁₅H₁₈O₂
• 分子量: 230.307
• InChiKey: BJWUYEGSLPUVHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  (1-重氮基-2-氧代丙基)膦酸二甲酯 、 (±)-6-hydroxy-2,5,7,8-tetramethylchroman-2-carbaldehyde 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以88%的产率得到(S)-(+)2-ethynyl-3,4-dihydro-2,5,7,8-tetramethyl-2H-benzopyran-6-ol
  参考文献：
  名称：

  Design and synthesis of novel neuroprotective 1,2-dithiolane/chroman hybrids

  摘要：

  Novel 1,2-dithiolane/chroman hybrids bearing heterocyclic rings such as 1,2,4- and 1,3,4-oxadiazole, 1,2,3-triazole and tetrazole were designed and synthesized. The neuroprotective activity of the new analogues was tested against oxidative stress-induced cell death of glutamate-challenged HT22 hippocampal neurons. Our results show that bioisosteric replacement of amide group in 2-position of the chroman moiety, by 1,3,4- oxadiazole did not affect activity. However, analogue 5 bearing the 1,2,4- oxadiazole moiety showed improved neuroprotective activity. The presence of nitrogen heterocycles strongly influences the neuroprotective activity of 5-substituted chroman derivatives, depending on the nature of heterocycle. Replacement of the amide group of the first generation analogues by 1,2,4- oxadiazole or 1,2,3-triazole resulted in significant improvement of the activity against glutamate induced oxidative stress. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.010

文献信息

• Treatment of mitochondrial diseases
  申请人：Walkinshaw Gail

  公开号：US20050065099A1

  公开（公告）日：2005-03-24

  The invention relates the method of treatment or amelioration of mitochondrial disorders such as Alzheimer's disease, Parkinson's disease, Friedreich's ataxia (FRDA), cerebellar ataxias, Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Myoclonic Epilepsy with Ragged Red Fibers (MERFF), amyotrophic lateral sclerosis (ALS), motor neuron diseases, Huntington's disease, macular degeneration, and epilepsy, with chroman derivatives of Formula I or Formula II as described herein.

  这项发明涉及治疗或改善线粒体疾病，如阿尔茨海默病、帕金森病、弗里德雷希共济失调症（FRDA）、小脑共济失调、勒伯遗传性视神经病变（LHON）、线粒体肌病、脑病、乳酸中毒、中风（MELAS）、带有红色纤维的肌阵挛性癫痫（MERFF）、肌萎缩侧索硬化症（ALS）、运动神经元疾病、亨廷顿病、黄斑变性和癫痫等疾病的治疗方法，所述方法使用本文描述的Formula I或Formula II的类胡萝卜素衍生物。
• Triazolo(4,3-A)(1,4)benzodiazepines and thieno
  申请人：Hoffmann-La Roche Inc.

  公开号：US04959361A1

  公开（公告）日：1990-09-25

  The invention relates to compounds of the formula ##STR1## wherein X is --CH.dbd.CH-- or S; R.sub.1 is lower alkyl, lower alkoxy or trifluoromethyl; R.sub.2 is hydrogen, lower alkyl, lower alkoxy, hydroxy or alkanoyloxy; R.sub.3 and R.sub.4, independently, are hydrogen, chlorine, fluorine, lower alkyl or lower alkoxy; s is an integer from 0 to 1, provided that when s is 1, R.sub.2 cannot be hydroxy, lower alkoxy or alkanoyloxy; R.sub.5 is a radical of the formula R.sub.6 --(CH.sub.2).sub.n -- or R.sub.7 --O--(CH.sub.2).sub.m -- wherein R.sub.6 and R.sub.7 are aryl or a heterocyclic radical, n is an integer of from 0 to 2 and m is an integer of from 1 to 2, provided that, when n is 0, R.sub.6 must be attached through a carbon to carbon bond, and provided that R.sub.7 is always attached through a carbon to oxygen bond, and, when at least one asymmetric carbon is present, its enantiomers and racemates, and pharmaceutically acceptable acid addition salts thereof. The compounds of formula I exhibit activity as platelet activating factor (PAF) antagonists and are, therefore, useful in disease states characterized by excess platelet activating factor or for the prevention and treatment of cardiovascular diseases, pulmonary diseases, immunological disorders, inflammatory diseases, dermatological disorders, shock or transplant rejection.

  本发明涉及公式##STR1##的化合物，其中X为--CH.dbd.CH--或S；R.sub.1为较低的烷基，较低的烷氧基或三氟甲基；R.sub.2为氢，较低的烷基，较低的烷氧基，羟基或脂肪酰氧基；R.sub.3和R.sub.4分别为氢，氯，氟，较低的烷基或较低的烷氧基；s为0至1的整数，但当s为1时，R.sub.2不能为羟基，较低的烷氧基或脂肪酰氧基；R.sub.5为公式R.sub.6 --(CH.sub.2).sub.n --或R.sub.7 --O--(CH.sub.2).sub.m --的基团，其中R.sub.6和R.sub.7为芳基或杂环基，n为0至2的整数，m为1至2的整数，但当n为0时，R.sub.6必须通过碳与碳键连接，且当至少存在一个不对称碳时，其对映异构体和外消旋体以及药学上可接受的酸加合物盐。公式I的化合物表现出血小板活化因子（PAF）拮抗剂的活性，因此在具有过多血小板活化因子的疾病状态或用于预防和治疗心血管疾病，肺部疾病，免疫障碍，炎症性疾病，皮肤疾病，休克或移植排斥反应等方面有用。
• 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。
• TREATMENT OF MITOCHONDRIAL DISEASES
  申请人：Ampere Life Sciences, Inc.

  公开号：US20130267538A1

  公开（公告）日：2013-10-10

  The invention relates the method of treatment or amelioration of mitochondrial disorders such as Alzheimer's disease, Parkinson's disease, Friedreich's ataxia (FRDA), cerebellar ataxias, Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, stroke (MELAS), Myoclonic Epilepsy with Ragged Red Fibers (MERFF), amyotrophic lateral sclerosis (ALS), motor neuron diseases, Huntington's disease, macular degeneration, and epilepsy, with chroman derivatives of Formula I or Formula II as described herein.

  本发明涉及使用式I或式II所描述的色酮衍生物的治疗或改善线粒体疾病的方法，例如阿尔茨海默病、帕金森病、弗里德雷希共济失调症（FRDA）、小脑共济失调、勒伯遗传性视神经病变（LHON）、线粒体肌病、脑病、乳酸中毒、中风（MELAS）、带红纤维的肌阵挛性癫痫（MERFF）、肌萎缩侧索硬化症（ALS）、运动神经元疾病、亨廷顿病、黄斑退化和癫痫。
• A novel approach to produce natural vitamin E making use of an asymmetric synthesis
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0320777A2

  公开（公告）日：1989-06-21

  A new approach to produce vitamin E in optically active pure form involving an asymmetric synthesis and novel intermediates therein.

  生产纯光学活性维生素 E 的新方法，涉及不对称合成及其新型中间体。