5-(1,8-Dihydroxy-9-oxo-9,10-dihydro-anthracen-2-yl)-pentanoic acid methyl ester | 186394-36-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 英文名称: 5-(1,8-Dihydroxy-9-oxo-9,10-dihydro-anthracen-2-yl)-pentanoic acid methyl ester
• 英文别名: methyl 5-(1,8-dihydroxy-9-oxo-10H-anthracen-2-yl)pentanoate
• CAS: 186394-36-5
• 化学式: C₂₀H₂₀O₅
• 分子量: 340.376
• InChiKey: FIALOVSVBOBSHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(1,8-Dihydroxy-9-oxo-9,10-dihydro-anthracen-2-yl)-pentanoic acid methyl ester 在 盐酸羟胺 、 sodium methylate 作用下， 以 甲醇 为溶剂， 以21%的产率得到5-(1,8-Dihydroxy-9-oxo-9,10-dihydro-anthracen-2-yl)-pentanoic acid hydroxyamide
  参考文献：
  名称：

  Antipsoriatic Anthrones with Modulated Redox Properties. 4. Synthesis and Biological Activity of Novel 9,10-Dihydro-1,8-dihydroxy-9-oxo-2- anthracenecarboxylic and -hydroxamic Acids

  摘要：

  A novel series of carboxylic and hydroxamic acids based on 1,8-dihydroxy-9(10H)-anthracenone were synthesized from 8-hydroxy-1-methoxy-9,10-anthracenedione as the key intermediate and evaluated both in the bovine polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay and in the HaCaT keratinocyte proliferation assay for their enzyme inhibitory and antiproliferative activity, respectively. The most potent inhibitors in both assays were the N-methylated hydroxamic acids 5d-8d with straight chain alkyl spacers. Incorporation of these structural features on the anthracenone pharmacophore resulted in increased inhibitory activity against 5-LO while the antiproliferative activity was retained. In addition, prooxidant properties as measured by deoxyribose degradation and cytotoxicity as assessed by LDH release were largely reduced as compared with the antipsoriatic anthralin. Contrary to anthralin, antioxidant properties were observed as documented by the reactivity of the novel compounds against free radicals and inhibition of lipid peroxidation in model membranes.

  DOI：

  10.1021/jm9701785
• 作为产物：
  描述：

  5-(9,10-dihydro-1,8-dihydroxy-9,10-dioxo-2-anthracene)-valeronitrile 在 盐酸 、 硫酸 、 溶剂黄146 、 tin(ll) chloride 作用下， 反应 6.0h， 生成 5-(1,8-Dihydroxy-9-oxo-9,10-dihydro-anthracen-2-yl)-pentanoic acid methyl ester
  参考文献：
  名称：

  Antipsoriatic Anthrones with Modulated Redox Properties. 4. Synthesis and Biological Activity of Novel 9,10-Dihydro-1,8-dihydroxy-9-oxo-2- anthracenecarboxylic and -hydroxamic Acids

  摘要：

  A novel series of carboxylic and hydroxamic acids based on 1,8-dihydroxy-9(10H)-anthracenone were synthesized from 8-hydroxy-1-methoxy-9,10-anthracenedione as the key intermediate and evaluated both in the bovine polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay and in the HaCaT keratinocyte proliferation assay for their enzyme inhibitory and antiproliferative activity, respectively. The most potent inhibitors in both assays were the N-methylated hydroxamic acids 5d-8d with straight chain alkyl spacers. Incorporation of these structural features on the anthracenone pharmacophore resulted in increased inhibitory activity against 5-LO while the antiproliferative activity was retained. In addition, prooxidant properties as measured by deoxyribose degradation and cytotoxicity as assessed by LDH release were largely reduced as compared with the antipsoriatic anthralin. Contrary to anthralin, antioxidant properties were observed as documented by the reactivity of the novel compounds against free radicals and inhibition of lipid peroxidation in model membranes.

  DOI：

  10.1021/jm9701785

文献信息

• [EN] 2-SUBSTITUTED 1,8-DIHYDROXY-9(10H)-ANTRACENONE AS PROLIFERATION AND 5-LIPOXYGENASE INHIBITORS<br/>[FR] 1,8-DIHYDROXY-9(10H)-ANTHRACENONE SUBSTITUEE EN POSITION 2 UTILISEE COMME INHIBITEUR DE PROLIFERATION ET DE 5-LIPOXYGENASE
  申请人：TEVA PHARMACEUTICAL INDUSTRIES LTD.

  公开号：WO1996040623A1

  公开（公告）日：1996-12-19

  (EN) 2-substituted 1,8-dihydroxy-9(10H)-antrhacenones of general formula (I), therapeutic compositions containing at least one 2-substituted 1,8-dihydroxy-9(10H)-anthracenone compound and methods of treating inflammatory conditions especially psoriasis are provided. In said formula, Y represents a linear or branched chain alkyl group having 1 to 10 carbon atoms, a phenylalkyl group having 7 to 10 carbon atoms, a phenylacyl group having 7 to 10 carbon atoms, an amino group, or an amino group substituted with a linear or branched chain alkyl group having 1 to 10 carbon atoms; and X represents a hydroxyl group, an ester group substituted with a straight or branched chain alkyl group having 1 to 10 carbon atoms, an amino group, amino group substituted with a straight or branched chain alkyl group having 1 to 10 carbon atoms, a hydroxilamine group, or an N-alkyl substituted hydroxylamine, said N-alkyl being straight or branched chain and having 1 to 10 carbon atoms, with the proviso that when X is hydroxyl, Y is not an alkyl group having 1 to 3 carbon atoms or CH2 Phenyl-4.(FR) La présente invention concerne des 1,8-dihydroxy-9(10H)-anthracénones substituées en position 2 représentées par la formule générale (I), des compositions thérapeutiques contenant au moins un composé de 1,8-dihydroxy-9(10H)-anthracénone substituée en position 2 ainsi que des procédés de traitement d'états inflammatoires, et notamment du psoriasis. Dans la formule (I), Y représente un groupe alkyle à chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, un groupe phénylalkyle ayant de 7 à 10 atomes de carbone, un groupe phénylacyle ayant de 7 à 10 atomes de carbone, un groupe amino, ou un groupe amino substitué par un groupe alkyle à chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, et X représente un groupe hydroxyle, un groupe ester substitué par un groupe alkyle à chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, un groupe amino, un groupe amino amino substitué par un groupe alkyle à chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, un groupe hydroxylamine ou une hydroxylamine N-alkyle substituée, ledit N-alkyle étant une chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, à condition que lorsque X est hydroxyle, Y ne soit pas un groupe alkyle ayant de 1 à 3 atomes de carbone ou CH2 phényl-4.

  (EN) 2-取代的 1,8-二羟基-9(10H)-抗reneone般公式 (I)，至少含有一种2-取代的1,8-二羟基-9(10H)- Anthracen-one化合物的治疗组合物及治疗炎性病症，特别是湿药疹的方法。在所述公式中，Y表示直链或分链烷基（具有1至10个碳原子），苯基烷基（具有7至10个碳原子），苯基炔基（具有7至10个碳原子），氨基，或氨基取代的直链或分链烷基（具有1至10个碳原子）；而X表示羟基，羟基取代的直链或分链烷基（具有1至10个碳原子），氨基，氨基取代的直链或分链烷基（具有1至10个碳原子）， 羟氨基，或 N-甲基取代的羟氨基，此 N-甲基表示为直链或分链，具有1至10个碳原子，且申明，当X是羟基时，Y不是具有1至3个碳原子的烷基或 CH2-PhenYl-4。 (FR) Cette invention concerne des 1,8-dihydroxy-9(10H)-anthracénones substitués en position 2 représentés par la formule générale (I), des compositions thérapeutiques contenant au moins un composé de 1,8-dihydroxy-9(10H)-anthracénone substitué en position 2 ainsi que des procédés de traitement d'états inflammatoires, et notamment du psoriasis. Dans la formule (I), Y représente un groupe alkyle à chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, un groupe phénylalkyle ayant de 7 à 10 atomes de carbone, un groupe phénylacyle ayant de 7 à 10 atomes de carbone, un groupe amino, ou un groupe amino substitué par un groupe alkyle à chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, et X représente un groupe hydroxyle, un groupe ester substitué par un groupe alkyle à chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, un groupe amino, un groupe amino amino substitué par un groupe alkyle à chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, un groupe hydroxylamine ou une hydroxylamine N-alkyle substitué, ledit N-alkyle étant une chaîne linéaire ou ramifiée ayant de 1 à 10 atomes de carbone, à condition que lorsque X est hydroxyle, Y ne soit pas un groupe alkyle ayant de 1 à 3 atomes de carbone ou CH2 phényl-4.
• US5922891A
  申请人：——

  公开号：US5922891A

  公开（公告）日：1999-07-13
• Antipsoriatic Anthrones with Modulated Redox Properties. 4. Synthesis and Biological Activity of Novel 9,10-Dihydro-1,8-dihydroxy-9-oxo-2- anthracenecarboxylic and -hydroxamic Acids
  作者：Klaus Müller、Helge Prinz

  DOI：10.1021/jm9701785

  日期：1997.8.1

  A novel series of carboxylic and hydroxamic acids based on 1,8-dihydroxy-9(10H)-anthracenone were synthesized from 8-hydroxy-1-methoxy-9,10-anthracenedione as the key intermediate and evaluated both in the bovine polymorphonuclear leukocyte 5-lipoxygenase (5-LO) assay and in the HaCaT keratinocyte proliferation assay for their enzyme inhibitory and antiproliferative activity, respectively. The most potent inhibitors in both assays were the N-methylated hydroxamic acids 5d-8d with straight chain alkyl spacers. Incorporation of these structural features on the anthracenone pharmacophore resulted in increased inhibitory activity against 5-LO while the antiproliferative activity was retained. In addition, prooxidant properties as measured by deoxyribose degradation and cytotoxicity as assessed by LDH release were largely reduced as compared with the antipsoriatic anthralin. Contrary to anthralin, antioxidant properties were observed as documented by the reactivity of the novel compounds against free radicals and inhibition of lipid peroxidation in model membranes.