4,6-Di-tert-Butyl-2,2-Di-n-Butyl-5-Hydroxy-2,3-Dihydrobenzofuran | 157360-05-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 4,6-Di-tert-Butyl-2,2-Di-n-Butyl-5-Hydroxy-2,3-Dihydrobenzofuran
• 英文别名: 4,6-di-t-butyl-2,2-di-n-butyl-5-hydroxy-2,3-dihydrobenzofuran；4,6-di-t-butyl-5-hydroxy-2,2-di-n-butyl-2,3-dihydrobenzofuran；5-Benzofuranol, 2,2-dibutyl-4,6-bis(1,1-dimethylethyl)-2,3-dihydro-；2,2-dibutyl-4,6-ditert-butyl-3H-1-benzofuran-5-ol
• CAS: 157360-05-9
• 化学式: C₂₄H₄₀O₂
• 分子量: 360.58
• InChiKey: UYJVQPVZUMEFJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2,6-二叔丁基-4-甲氧基苯酚 在 lithium aluminium tetrahydride 、 碘代三甲硅烷 、 (CH₂)6N₄ 、 硫酸 、 三氟化硼乙醚 、 magnesium 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 110.5h， 生成 4,6-Di-tert-Butyl-2,2-Di-n-Butyl-5-Hydroxy-2,3-Dihydrobenzofuran
  参考文献：
  名称：

  Design and Synthesis of 4,6-Di-tert-butyl-2,3-dihydro-5-benzofuranols as a Novel Series of Antiatherogenic Antioxidants

  摘要：

  Antioxidants have been considered as potential antiatherogenic agents by inhibiting oxidation of low-density lipoprotein (LDL), albeit vitamin E, a natural antioxidant, has failed to show reduction on atherosclerosis in clinical trials. We have rationally designed and synthesized a novel series of antioxidants, 4,6-di-tert-butyl-2,3-dihydro-5-benzofuranols, to overcome the clinical limitation of vitamin E. In vitro, the compounds showed a potent inhibitory effect on lipid peroxidation detected as 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazin3-one (MCLA)-dependent chemiluminescence in linoleic acid autoxidation. They also inhibited the LDL oxidation induced by Cu2+, and the inhibition is more potent than that of vitamin E and probucol. In vivo, 4,6-di-tert-butyl-2,3-dihydro-2,2-dipentyl-5-benzofuranoI (BO-653, 1f), an optimal compound, showed the highest concentration in plasma and LDL fraction in Watanabe heritable hyperlipidemic rabbits, due to its high affinity to LDL. The isolated LDL samples from the If-treated rabbits showed potent resistibility to LDL oxidation. Compound If has been taken into clinical trials.

  DOI：

  10.1021/jm030062a

文献信息

• INTIMAL THICKENING INHIBITOR
  申请人：Chugai Seiyaku Kabushiki Kaisha

  公开号：EP0868913A1

  公开（公告）日：1998-10-07

  An intimal thickening inhibitory agent comprising, as an active ingredient, a compound represented by formula (1): wherein X represents an oxygen atom or a group of formula (2): wherein n represents an integer of from 0 to 2, R1 represents a hydrogen atom or an acyl group; R2 represents a hydrogen atom, a lower alkyl group or a lower alkenyl group; R3 represents a lower alkyl group; and R4, R5, and R6, which may be the same or different, each represent a hydrogen atom or a substituted or unsubstituted alkyl group; or R3 and R4 may be taken together to form a 5-membered ring; or R5 and R6 may be taken together to form a cycloalkyl group; provided that R6 is nil when R3 and R4 are taken together to form benzofuran or benzo[b]thiophene.

  一种内膜增厚抑制剂，其活性成分包括由式（1）代表的化合物： 其中 X 代表氧原子或式（2）的基团： 其中 n 代表 0 至 2 的整数、 R1 代表氢原子或酰基； R2 代表氢原子、低级烷基或低级烯基； R3 代表低级烷基； R4、R5 和 R6 可以相同或不同，各自代表氢原子或取代或未取代的烷基；或 R3 和 R4 组合在一起形成五元环；或 R5 和 R6 组合在一起形成环烷基；但当 R3 和 R4 组合在一起形成苯并呋喃或苯并[b]噻吩时，R6 为零。
• REMEDIES FOR RENAL DISEASES AND ORGAN-PRESERVING AGENTS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0950405A1

  公开（公告）日：1999-10-20

  Herein disclosed are therapeutic agents for renal diseases and organ preservatives containing a compound represented by the general formula (1): wherein X represents an oxygen atom or a group represented by the general formula (2): where n represents an integer from 0 to 2, R1 represents a hydrogen atom or an acyl group, R2 represents a hydrogen atom, a lower alkyl group or a lower alkenyl group, R3 represents a lower alkyl group, R4, R5 and R6, which may be the same or different, each represents a hydrogen atom or an optionally substituted alkyl group, and R6 further represents a formyl, carboxyl, lower alkoxycarbonyl or optionally substituted carbamoyl group, or R3 and R4 may be taken together to form a five-membered ring, or R5 and R6 may be taken together to form a cycloalkyl group, provided that when the five-membered ring formed by R3 and R4 and the benzene ring form benzofuran or benzo[b]thiophene, R6 is absent.

  这里公开的是含有通式（1）所代表的化合物的肾病治疗剂和器官防腐剂： 其中 X 代表氧原子或通式（2）所代表的基团： 其中 n 代表 0 至 2 的整数，R1 代表氢原子或酰基，R2 代表氢原子、低级烷基或低级烯基，R3 代表低级烷基，R4、R5 和 R6 可以相同或不同，各自代表氢原子或任选取代的烷基，R6 进一步代表甲酰基、羧基、低级烷氧基羰基或低级烷氧基羰基、羧基、低级烷氧基羰基或任选取代的氨基甲酰基，或 R3 和 R4 可结合在一起形成五元环，或 R5 和 R6 可结合在一起形成环烷基，但当 R3 和 R4 形成的五元环与苯环形成苯并呋喃或苯并[b]噻吩时，R6 不存在。
• PREVENTIVES/REMEDIES FOR ARTERIOSCLEROSIS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP0982029A1

  公开（公告）日：2000-03-01

  Herein disclosed are prophylactic/therapeutic agents for atherosclerosis containing a compound of general formula (1): wherein R1 represents a hydrogen atom or an acyl group, R2 represents a lower alkyl group, R3 represents a hydrogen atom or a lower alkyl group, and R4, R5 and R6 represent a hydrogen atom, an alkyl group, an alkenyl group, an alkynyl group or an aryl group, or R2 and R4 together with the oxygen atom may form a furan or dihydrofuran ring, or R5 and R6 may combine to form a cycloalkyl group or a heterosubstituted cycloalkyl group in which one or more methylene groups of the cycloalkyl group are replaced by oxygen, sulfur or alkyl-substituted nitrogen atoms, a possible optically active isomer or a pharmaceutically acceptable salt thereof, as an active ingredient.

  本发明公开了含有通式（1）化合物的动脉粥样硬化预防/治疗剂： 其中 R1 代表氢原子或酰基，R2 代表低级烷基，R3 代表氢原子或低级烷基，R4、R5 和 R6 代表氢原子、烷基、烯基、炔基或芳基，或 R2 和 R4 与氧原子一起可形成呋喃或二氢呋喃环、或 R5 和 R6 可结合形成环烷基或杂取代的环烷基，其中环烷基的一个或多个亚甲基被氧、硫或烷基取代的氮原子、可能的光学活性异构体或其药学上可接受的盐取代，作为活性成分。
• SEAMLESS SOFT CAPSULE PREPARATIONS CONTAINING DIHYDROBENZOFURAN DERIVATIVES
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1314424A1

  公开（公告）日：2003-05-28

  The invention provides seamless soft capsule formulations characterized by comprising dihydrobenzofuran derivatives represented by general formula (1): wherein R1 represents hydrogen or an acyl group, R2 represents hydrogen or a lower alkyl group and R3 and R4 may be the same or different and each represents one selected from the group consisting of hydrogen, optionally substituted alkyl groups, optionally substituted alkenyl groups, optionally substituted alkynyl groups, optionally substituted aryl groups and optionally substituted arylalkyl groups. The seamless soft capsule formulations provide excellent stability by adequately preventing degradation by oxidation and the like.

  本发明提供了无缝软胶囊制剂，其特征在于包含通式（1）所代表的二氢苯并呋喃衍生物： 其中 R1 代表氢或酰基，R2 代表氢或低级烷基，R3 和 R4 可以相同或不同，并且各自代表选自氢、任选取代的烷基、任选取代的烯基、任选取代的炔基、任选取代的芳基和任选取代的芳烷基组成的组中的一个。无缝软胶囊制剂具有极佳的稳定性，可充分防止氧化等降解作用。
• APOLIPO PROTEIN E SECRETION PROMOTERS
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP1428529A1

  公开（公告）日：2004-06-16

  A pharmaceutical composition comprising a compound represented by the following formula: which promote the secretion of ApoE, lower the onset frequency of acute coronary syndrome or relieve the symptom thereof, and lower intracellular lipid conten; and a method therefor are provided. Moreover, a use of a compound of formula (1) in manufacturing the above pharmaceutical composition is also provided.

  本发明提供了一种药物组合物，该药物组合物包含由下式代表的化合物： 本发明提供了一种药物组合物，该组合物能促进载脂蛋白的分泌，降低急性冠状动脉综合征的发病频率或缓解其症状，并降低细胞内脂质含量；还提供了一种使用该组合物的方法。此外，还提供了式(1)化合物在制造上述药物组合物中的用途。