2-methyl-2-(4-methylpentyl)chroman-6-ol | 1547258-93-4

• 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: 2-methyl-2-(4-methylpentyl)chroman-6-ol
• 英文别名: 2-Methyl-2-(4-methylpentyl)-3,4-dihydrochromen-6-ol；2-methyl-2-(4-methylpentyl)-3,4-dihydrochromen-6-ol
• CAS: 1547258-93-4
• 化学式: C₁₆H₂₄O₂
• 分子量: 248.365
• InChiKey: IGHJAWFSPCPFFM-UHFFFAOYSA-N

物化性质

• 沸点：
  369.1±31.0 °C(predicted)
• 密度：
  1.000±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  6-hydroxy-2-methyl-2-(4-methylpentyl)chroman-4-one 在 盐酸 、 锌 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 生成 2-methyl-2-(4-methylpentyl)chroman-6-ol
  参考文献：
  名称：

  Exploitation of the Ability of γ-Tocopherol to Facilitate Membrane Co-localization of Akt and PHLPP1 to Develop PHLPP1-Targeted Akt Inhibitors

  摘要：

  Previously, we reported that Akt inactivation by gamma-tocopherol (2) in PTEN-negative prostate cancer cells resulted from its unique ability to facilitate membrane co-localization of Akt and PHLPP1 (PH domain leucine-rich repeat protein phosphatase isoform 1), a Ser473-specific Akt phosphatase, through pleckstrin homology (PH) domain binding. This finding provided a basis for exploiting 2 to develop a novel class of PHLPP1-targeted Akt inhibitors. Here, we used 3 (gamma-VE5), a side chain-truncated 2 derivative, as a scaffold for lead optimization. The proof-of-concept of this structural optimization was obtained by 20, which exhibited higher antitumor efficacy than 3 in PTEN-negative cancer cells through PHLPP1-facilitated Akt inactivation. Like 3, 20 preferentially recognized the PH domains of Akt and PHLPP1, as its binding affinities for other PH domains, including those of ILK and PDK1, were an order-of-magnitude lower. Moreover, 20 was orally active in suppressing xenograft tumor growth in nude mice, which underlines the translational potential of this new class of Akt inhibitor in PTEN-deficient cancers.

  DOI：

  10.1021/jm501751b

文献信息

• AKT INACTIVATION BY TOCOPHERYL DERIVATIVES
  申请人：Chen Ching-Shih

  公开号：US20140031388A1

  公开（公告）日：2014-01-30

  Anticancer compounds according to formula I are described herein. wherein R 1 , R 2 , R 3 and R 4 are selected from H, CH 3 , OH, SH, OCH 3 , NHR′, halogen, CF 3 , N-linked pyrrolidine, and SO 2 NHR′, or any combination thereof; R 5 is an alkyl, alkenyl, or alkaryl group including from 4 to 11 carbons, X is selected from CH 2 , CHOH, C═O, S═O, O═S═O, and an oxetane ring, Y is selected from CH 2 , O, and NH, and R′ is a H, aryl, or a lower alkyl group, or pharmaceutically acceptable salts thereof. The compounds have been shown to facilitate site-specific dephosphorylation of Akt at Ser-473, thereby inactivating Akt and decreasing dysregulation of Akt signaling that can occur in cancer cells.

  根据公式 I，这里描述的抗癌化合物。其中 R1、R2、R3 和 R4 从 H、CH3、OH、SH、OCH3、NHR′、卤素、CF3、N-连接吡咯烷和SO2NHR′ 中选择，或其任意组合；R5 是包括 4 到 11 个碳的烷基、烯基或烷基芳基基团，X 从 CH2、CHOH、C═O、S═O、O═S═O 和氧杂环戒中选择，Y 从 CH2、O 和 NH 中选择，R′ 是 H、芳基或较低烷基基团，或其药用可接受盐。这些化合物已被证明有助于在 Ser-473 处促进 Akt 的位点特异性去磷酸化，从而使 Akt 失活，并减少癌细胞中可能发生的 Akt 信号传导失调。
• NOVEL USE OF SUBSTITUTED CHROMAN-6-OLS
  申请人：DSM IP ASSETS B.V.

  公开号：US20210030022A1

  公开（公告）日：2021-02-04

  The present invention is directed towards the use of substituted chroman-6-ols of formula (I) wherein R 1 and R 2 are independently from each other H or C 1-11 -alkyl or (CH 2 ) n —OH with n being an integer from 1 to 4, or R 1 and R 2 represent together a keto group, 10 A is CHR 3 or C(═O), and wherein R 3 , R 4 and R 6 are independently from each other H or C 1-4 -alkyl, and wherein R 5 is H or OH or C 1-4 -alkyl or C 1-4 -alkoxy, as antioxidants, especially in feed such as pet food and feed ingredients such as fish meal, insect meal and poultry meal, as well as PUFA-containing oil such as marine oil, microbial oil, fungal oil, algal oil and PUFA-containing plant oil. The present invention is further directed towards feed ingredients and feed for insects, aquatic and terrestrial animals comprising such substituted chroman-6-ols of formula (I).

  本发明涉及使用式(I)的取代基氧杂环己烯-6-醇，其中R1和R2分别独立地为H或C1-11-烷基或(CH2)n—OH，其中n为1至4的整数，或者R1和R2共同表示酮基，A为CHR3或C(═O)，其中R3、R4和R6分别独立地为H或C1-4-烷基，R5为H或OH或C1-4-烷基或C1-4-烷氧基，作为抗氧化剂，特别是在饲料中，如宠物食品和饲料成分，如鱼粉、昆虫粉和禽畜粉，以及富含PUFA的油，如海洋油、微生物油、真菌油、藻类油和富含PUFA的植物油。本发明还涉及含有式(I)的这种取代基氧杂环己烯-6-醇的饲料成分和用于昆虫、水生和陆生动物的饲料。
• [EN] CHROMAN-6-OLS WITH AN EXTENDED LIPOPHILIC SIDE CHAIN IN POSITION 2, THEIR MANUFACTURE AND USE<br/>[FR] CHROMAN-6-OLS À CHAÎNE LATÉRALE LIPOPHILE ÉTENDUE EN POSITION 2, LEUR FABRICATION ET LEUR UTILISATION
  申请人：DSM IP ASSETS BV

  公开号：WO2019185904A1

  公开（公告）日：2019-10-03

  The present invention is directed to a process for the manufacture of a compound of formula (III), comprising the step of reacting a compound of formula (I) with a compound of formula (II) in the presence of an acid catalyst and in a mixture of two solvents, wherein n is 1 or 2, and R1 and R3 are independently from each other H or C1-5-alkyl, and R2 is either H or C1-5-alkyl or C1-5-alkyloxy, preferably with the proviso that at least one of R1, R2 and R3 is H, and wherein the first of the two solvents is selected from ethylene carbonate, propylene carbonate, 1,2-butylene carbonate, gamma-butyrolactone and water, and the second of the two solvents is selected from hexane, cyclohexane, heptane, ortho-xylene, meta-xylene, para-xylene, mesitylene, pseudocumene, methyl tert-butyl ether, and toluene. The present invention is also directed to the compound of formula (III-3), as well as to the use of compounds of formula (III), especially to the use of compound of formula (III-3) and the use of compound of formula (III-4), as antioxidants, especially in feed, such as e.g. in feed for aquatic animals, in feed for terrestrial animals (especially pet food, feed for pigs and feed for poultry) and in feed for insects, and in feed ingredients, such as in fish meal, in poultry meal, in insect meal, and in PUFA-containing oils such as marine oil, microbial oil, fungal oil, algal oil and PUFA-containing plant oil The present invention is further directed towards feed and feed ingredients containing at least one compound of formula (III), especially containing a compound of formula (III-3) and/or a compound of formula (III-4).

  本发明涉及一种制备式（III）化合物的方法，包括在两种溶剂的混合物中，在酸催化剂的存在下，将式（I）化合物与式（II）化合物反应，其中n为1或2，R1和R3独立地为H或C1-5-烷基，R2为H或C1-5-烷基或C1-5-烷氧基，优选至少其中之一为H，其中第一种溶剂选自碳酸乙烯酯、碳酸丙烯酯、1,2-丁二酸酯、γ-丁内酯和水，第二种溶剂选自己烷、环己烷、庚烷、邻二甲苯、间二甲苯、对二甲苯、三甲苯、假叔丁醚和甲苯。本发明还涉及式（III-3）化合物的制备方法，以及化合物式（III）的用途，特别是化合物式（III-3）和化合物式（III-4）作为抗氧化剂的用途，特别是在饲料中的用途，例如在水生动物饲料、陆生动物饲料（特别是宠物食品、猪饲料和禽饲料）和昆虫饲料中，以及在饲料成分中，例如在鱼粉、禽粉、昆虫粉和富含PUFA的油中，例如海洋油、微生物油、真菌油、藻油和富含PUFA的植物油。本发明还涉及至少含有一种式（III）化合物的饲料和饲料成分，特别是含有化合物式（III-3）和/或化合物式（III-4）的饲料和饲料成分。
• CHROMAN-6-OLS WITH AN EXTENDED LIPOPHILIC SIDE CHAIN IN POSITION 2, THEIR MANUFACTURE AND USE
  申请人：DSM IP Assets B.V.

  公开号：EP3774757A1

  公开（公告）日：2021-02-17
• [EN] NOVEL USE OF SUBSTITUTED CHROMAN-6-OLS<br/>[FR] NOUVELLE UTILISATION DE CHROMAN-6-OLS SUBSTITUÉS
  申请人：DSM IP ASSETS BV

  公开号：WO2019185894A1

  公开（公告）日：2019-10-03

  The present invention is directed towards the use of substituted chroman-6- ols of formula (I) wherein R1 and R2 are independently from each other H or C1-11-alkyl or (CH2)n─OH with n being an integer from 1 to 4, or R1 and R2 represent together a keto group, 10 A is CHR3 or C(=O), and wherein R3, R4 and R6 are independently from each other H or C1-4-alkyl, and wherein R5 is H or OH or C1-4-alkyl or C1-4-alkoxy, as antioxidants, especially in feed such as pet food and feed ingredients such as fish meal, insect meal and poultry meal, as well as PUFA-containing oil such as marine oil, microbial oil, fungal oil, algal oil and PUFA-containing plant oil. The present invention is further directed towards feed ingredients and feed for insects, aquatic and terrestrial animals comprising such substituted chroman-6-ols of formula (I).