4-hydroxy methyl all-trans retinoate | 38030-59-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 4-hydroxy methyl all-trans retinoate
• 英文别名: 4-(+/-)-hydroxy-(E)-methylretinoate；methyl 4-hydroxyretinoate；(13E)-3,7-dimethyl-9-(3-hydroxy-2,6,6-trimethylcyclohexenyl)-2,4,6,8-nontetraenoic acid methyl ester；Methyl-4-hydroxyretinoat；4-Hydroxyretinoic acid methyl ester；4-Hydroxymethylretinoat；4-Hydroxyretinoic Acid Methylester；methyl (2E,4E,6E,8E)-9-(3-hydroxy-2,6,6-trimethylcyclohexen-1-yl)-3,7-dimethylnona-2,4,6,8-tetraenoate
• CAS: 38030-59-0
• 化学式: C₂₁H₃₀O₃
• 分子量: 330.467
• InChiKey: RLAYPMFOLMBAIN-XPSLGPGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-hydroxy methyl all-trans retinoate 在 manganese(IV) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以84%的产率得到4-氧代全-反式-维甲酸甲基酯
  参考文献：
  名称：

  Retinoic acid metabolites. 1. Total synthesis of 4-hydroxy- and 4-oxoretinoic acid

  摘要：

  DOI：

  10.1021/jo00348a018
• 作为产物：
  描述：

  维A酸 在 manganese(IV) oxide 、 sodium tetrahydroborate 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 、 苯 为溶剂， 反应 25.25h， 生成 4-hydroxy methyl all-trans retinoate
  参考文献：
  名称：

  具有多种生物活性的新型视黄酸代谢阻断剂是人乳腺癌和前列腺癌细胞在体外的有效生长抑制剂，以及裸鼠中人乳腺癌的异种移植。

  摘要：

  新型视黄酸代谢阻断剂（RAMBAs）已经合成和表征。合成特征包括在全反式视黄酸（ATRA）和13-顺式视黄酸的C-4处引入亲核配体，以及修饰末端羧酸基团。我们的大多数化合物都是仓鼠肝微粒ATRA代谢酶的强效抑制剂。最有效的化合物是甲基（2E，4E，6E，8E）-9-（3-咪唑基-2,6,6-三甲基环己-1-烯基）-3,7-二甲基壬基-2，4,6,8-四烯酸酯（5）的IC（50）值为0.009 nM，比有名的RAMBA利拉唑（Liazal，IC（50）= 6000 nM）强666,667倍。出乎意料的是，化合物5的两种对映异构体的酶抑制活性之间基本没有差异。在MCF-7细胞增殖实验中，RAMBAs也以浓度依赖的方式增强ATRA介导的抗增殖活性。除了在微粒体制剂和完整的人类癌细胞（MCF-7，T47D和LNCaP）中作为ATRA代谢的高效抑制剂外，新型非典型RAMBAs还表现出多种生物学活性，

  DOI：

  10.1021/jm0401457

文献信息

• 一种烯酸杂质的制备方法
  申请人：重庆华邦胜凯制药有限公司

  公开号：CN112142635B

  公开（公告）日：2023-03-28

  本发明属于化学合成技术领域，具体涉及一种烯酸杂质的制备方法。所述杂质为(13E)‑3,7‑二甲基‑9‑【(3RS)‑3‑甲氧基‑2,6,6‑三甲基环己烯基】‑2,4,6,8‑壬四烯酸，所述制备方法为以(13E)‑3,7‑二甲基‑9‑(2,6,6‑三甲基环己烯基)‑2,4,6,8‑壬四烯酸为原料，在溶剂中通过酯化反应、氧化反应、还原反应、取代反应、水解反应得到一种烯酸杂质。所述方法具有合成路线短且清晰、纯化快速简便、所得产品纯度高的特点，可以用于维甲酸生产中杂质的定性和定量分析，从而提高维甲酸的质量标准，从而为安全用药提供重要的指导意义。
• [EN] 4-OXO-FENRETINIDE, ADMINISTERED ALONE AND IN COMBINATION WITH FENRETINIDE, AS PREVENTIVE AND THERAPEUTIC AGENT FOR CANCER<br/>[FR] 4-OXO-FENRETINIDE, ADMINISTRE SEUL ET EN COMBINAISON AVEC LE FENRETINIDE, COMME AGENT PREVENTIF ET THERAPEUTIQUE CONTRE LE CANCER
  申请人：IST NAZ STUD CURA DEI TUMORI

  公开号：WO2005092314A1

  公开（公告）日：2005-10-06

  A drug based on a metabolite of fenretinide, or N-(4­hydroxyphenyl)retinamide (4-HPR), specifically 4-oxo-N-(4­hydroxyphenyl)retinamide (4-oxo-4-HPR), is used in the treatment of different kinds of tumors, in particular in the treatment of ovarian carcinoma, breast tumor and neuroblastoma. The drug is more potent than fenretinide alone, and enhances the effects of fenretinide when administered together with fenretinide.

  一种基于芬烯酸代谢物或N-(4-羟基苯基)维甲酰胺(4-HPR)的药物，特别是4-氧代-N-(4-羟基苯基)维甲酰胺(4-oxo-4-HPR)，用于治疗不同类型的肿瘤，特别是卵巢癌、乳腺肿瘤和神经母细胞瘤。该药物比单独使用芬烯酸更具有强效，当与芬烯酸一起使用时，可以增强芬烯酸的效果。
• Novel deuterated Mnk1/2 protein degrader VNLG-152R analogs: Synthesis, In vitro Anti-TNBC activities and pharmacokinetics in mice
  作者：Puranik Purushottamachar、Elizabeth Thomas、Retheesh S. Thankan、Vincent C.O. Njar

  DOI：10.1016/j.ejmech.2022.114441

  日期：2022.8

  improved synthesis of lead Mnk1/2 protein degrader, VNLG-152R, 4-(±)-(1H-imidazole-1-yl)-N-(4-fluorophenyl)-(E)-retinamide (1) has been developed from commercially available 4-oxo-ATRA (8). This procedure was also utilized to synthesize the seven possible deuterated analogs of compound 1 (11–17). The deuterated analogs were either better or equipotent to 1 in in vitro antiproliferative activities against

  一种新的改进合成的铅 Mnk1/2 蛋白降解剂 VNLG-152R, 4-(±)-( 1H -imidazole -1-yl)- N -(4-fluorophenyl)-( E )-retinamide ( 1 )由市售的 4-oxo-ATRA ( 8 ) 开发而成。该程序还用于合成化合物1 ( 11 – 17 ) 的七种可能的氘代类似物。氘代类似物在体外更好或等效于1对 MDA-MB-231 和 MDA-MB-468 人 TNBC 细胞的抗增殖活性。Mnk1/2 降解剂与标准 TNBC 疗法（紫杉醇）同样有效。重要的是，Mnk1、peIF4E 及其相关下游靶标（包括细胞周期蛋白 D1 和 Bcl2）的表达在化合物1 /类似物 ( 11 – 17 ) 处理的 TNBC 细胞中显着降低，表明 Mnk1-eIF4E 信号传导受到抑制。更重要的是，我们发现氘代类似物12、16和17在向 CD-1
• Potent inhibition of retinoic acid metabolism enzyme(s) by novel azolyl retinoids
  作者：Vincent C.O Njar、Ivo P Nnane、Angela M.H Brodie

  DOI：10.1016/s0960-894x(00)00391-7

  日期：2000.9

  Novel (+/-)-4-azolyl retinoic acid analogues 4, 5, 7 and 8 have been designed and synthesized and have been shown to be powerful inhibitors of hamster microsomal all-trans-retinoic acid 4-hydroxylase enzyme(s). (+/-)-4-(1H-Imidazol-1-yl)retinoic acid (4) is the most potent inhibitor of this enzyme reported to date. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Free Radical Oxidation of (E)-Retinoic Acid by Prostaglandin H Synthase
  作者：Victor M. Samokyszyn、Tao Chen、Krishna Rao Maddipati、Thomas J. Franz、Paul A. Lehman、Roger V. Lloyd

  DOI：10.1021/tx00047a022

  日期：1995.7

  Cooxidative metabolism of all-trans (E)-retinoic acid (RA) by prostaglandin H synthase was investigated employing ram seminal vesicle microsomes (RSVM) or purified, RSVM-derived enzyme. RA was shown to undergo hydroperoxide [H2O2 or 5-phenyl-4-penten-1-yl hydroperoxide (PPHP)]- or arachidonic acid-dependent cooxidation by microsomal prostaglandin H (PGH) synthase as evidenced by UV spectroscopic analysis of reaction mixtures. Cooxidation of RA by microsomal or purified PGH synthase, using PPHP as substrate, was characterized by uptake of dioxygen which was first order with respect to enzyme concentration. Dioxygen uptake was inhibited by the peroxidase reducing substrate 2-methoxyphenol. In addition, O-2 uptake was inhibited by the spin trap nitrosobenzene. ESR spin trapping studies, using alpha-phenyl-N-tert-butylnitrone (PBN) as the spin trap, demonstrated the formation of RA-PBN adducts, characterized by hyperfine coupling constants of a(H) = 3.2 G and a(N) = 15.8 G. Reverse phase HPLC analysis of reaction mixtures demonstrated the formation of 4-hydroxy-RA, 5,6-epoxy-RA, 4-oxo-RA, (13Z)-retinoic acid, and other geometric isomers which were identified on the basis of cochromatography with synthetic standards, UV spectroscopy, and/or mass spectrometry. Mechanisms are proposed for the hydroperoxide-dependent, PGH synthase-catalyzed oxidation of RA that are consistent with these results.