2-(4-chlorobenzoyl)-4,4-diethylisoxazolidine-3,5-dione

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-chlorobenzoyl)-4,4-diethylisoxazolidine-3,5-dione
• 英文别名: 2-(4-chlorobenzoyl)-4,4-diethyl-1,2-oxazolidine-3,5-dione
• 化学式: C₁₄H₁₄ClNO₄
• 分子量: 295.722
• InChiKey: BGXQBKKMPCBDDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  63.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  二氯化二乙基丙二酰 在 盐酸 、 sodium carbonate 作用下， 以0.76 g (16.4%)的产率得到2-(4-chlorobenzoyl)-4,4-diethylisoxazolidine-3,5-dione
  参考文献：
  名称：

  Compounds for the control of hyperlipidemia using N-substituted

  摘要：

  一种用于控制哺乳动物高脂血症的异噁唑烷-3,5-二酮，具有以下结构式： 其中R.sup.1和R.sup.2各自是含有1至4个碳的烷基；R.sup.3是含有1至3个烷氧基的烷氧基苯甲酰基团，其中烷氧基含有1至4个碳原子，一种烷氧基苯甲酰基团，其中烷基团含有1至4个碳，一种卤代苯甲酰基团，或一种群 ##STR2## 其中R.sup.10和R.sup.11一起形成C.sub.3至C.sub.7烷基链，R.sup.12和R.sup.13各自是含有1至4个碳原子的烷基。

  公开号：

  US04946963A1

文献信息

• Isoxazolidine-3,5-diones, pharmaceutical compositions and method of
  申请人：The North Carolina Central Univ.

  公开号：US04999366A1

  公开（公告）日：1991-03-12

  A method of controlling hyperlipidemia in mammals which comprises adminstering to a mammal an amount effective to control hyperlipidemia of a compound having hypolipidemic activity and the structural formula: ##STR1## wherein R.sup.1 and R.sup.2, which may be the same or different provided both are not hydrogen when R.sup.3 is an alkenyl or cycloalkenyl group, are selected from the group consisting of hydrogen; alkyl of 1 to 18 carbons; substituted alkyl of 1 to 18 carbons; cycloalkyl of 4 to 10 ring carbon atoms; substituted cycloalky of 4 to 10 ring carbon stoms; alkoxy of 1 to 8 carbon atoms; amido; carbamoyl; acyloxy; alkoxycarbonyl; halogen, aryl and substituted aryl, or together R.sup.1 and R.sup.2 from a C.sub.3 to C.sub.7 alkylene group; and R.sup.3 is hydrogen; lower alkyl; substituted lower alkyl; cycloalkyl; substituted cyloalkyl; aryl; substituted aryl; a group --COR.sup.4 were R.sup.4 is hydrogen, lower alkyl, substituted lower alkyl, cycloalkyl, substituted cycloalkyl, aryl, or substituted aryl; a group --CONHR.sup.5 where R.sup.5 has the same meaning as R.sup.4 ; an alkoxycarbonyl group --CO.sub.2 R.sup.6 where R.sup.6 has the same meaning as R.sup.4 ; an alkenyl group --CR.sup.7 .dbd.CR.sup.8 R.sup.9 where R.sup.7, R.sup.8 and R.sup.9, which may be the same or different, have the same meaning as R.sup.4 ; a cycloalkenyl group ##STR2## where n is an integer from 3 to 8; or a group ##STR3## where R.sup.10 and R.sup.11 have the same meanings as R.sup.4 or together R.sup.10 and R.sup.11 form a C.sub.3 to C.sub.7 alkylene group, and R.sup.12 and R.sup.13, which may be the same or different, have the same meanings as R.sup.1 and R.sup.2, provided that R.sup.1 and R.sup.2 are not both hydrogen, the pharmaceutically acceptable salts, and mixtures thereof; and pharmaceutical compositions useful in practicing the method comprising the hypolipidemically active isoxazolidine-3,5-dione compounds and a pharmaceutically acceptable carrier.

  一种控制哺乳动物高脂血症的方法，包括向哺乳动物施用具有降脂活性的化合物，其结构式为：##STR1##其中R.sup.1和R.sup.2，可以相同也可以不同，当R.sup.3是烯丙基或环烯丙基时，两者都不是氢，从以下组中选择：氢; 1至18个碳的烷基; 1至18个碳的取代烷基; 4至10个环碳原子的环烷基; 取代的4至10个环碳原子的环烷基; 1至8个碳原子的烷氧基; 酰胺; 氨基甲酰; 酰氧基; 烷氧羰基; 卤素，芳基和取代芳基，或者R.sup.1和R.sup.2一起形成C.sub.3至C.sub.7烷基; R.sup.3是氢; 低烷基; 取代的低烷基; 环烷基; 取代的环烷基; 芳基; 取代的芳基; 一个--COR.sup.4的基团，其中R.sup.4是氢，低烷基，取代的低烷基，环烷基，取代的环烷基，芳基或取代的芳基; 一个--CONHR.sup.5基团，其中R.sup.5具有与R.sup.4相同的含义; 一个烷氧羰基基团--CO.sub.2R.sup.6，其中R.sup.6具有与R.sup.4相同的含义; 一个烯丙基基团--CR.sup.7 .dbd.CR.sup.8 R.sup.9，其中R.sup.7，R.sup.8和R.sup.9可以相同也可以不同，具有与R.sup.4相同的含义; 一个环烯丙基基团##STR2##其中n是从3到8的整数; 或者一个##STR3##其中R.sup.10和R.sup.11具有与R.sup.4相同的含义，或者一起形成C.sub.3至C.sub.7烷基，而R.sup.12和R.sup.13可以相同也可以不同，具有与R.sup.1和R.sup.2相同的含义，前提是R.sup.1和R.sup.2都不是氢，以及药学上可接受的盐和混合物; 以及在实践该方法时有用的具有降脂作用的异噁唑啉-3,5-二酮化合物和药学上可接受的载体的制药组合物。
• Isoxazolidine-3,5-diones in the treatment of hyperlipidemia
  申请人：THE UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL

  公开号：EP0321090A2

  公开（公告）日：1989-06-21

  A method of controlling hyperlipidemia in mammals which comprises administering to a mammal an amount effective to control hyperlipidemia of a compound having hypolipidemic activity and the structural formula: wherein R¹ and R², which may be the same or different provided both are not hydrogen when R³ is an alkenyl or cycloalkenyl group, are selected from the group consisting of hydrogen; alkyl of 1 to 18 carbons; substituted alkyl of 1 to 18 carbons; cycloalkyl of 4 to 10 ring carbon atoms; sub­stituted cycloalkyl of 4 to 10 ring carbon atoms; alkoxy of 1 to 8 carbon atoms; amido; carbamoyl; acyloxy; alkoxycarbonyl; halogen, aryl and substituted aryl, or together R¹ and R² form a C₃ to C₇ alkylene group; and R³ is hydrogen; lower alkyl; substituted lower alkyl; cycloalkyl; substituted cycloalkyl; aryl; substituted aryl; a group -COR⁴ where R⁴ is hydrogen, lower alkyl, substituted lower alkyl, cycloalkyl, substituted cycloalkyl, aryl, or substituted aryl; a group -CONHR⁵ where R⁵ has the same meaning as R⁴; an alkoxycarbonyl group -CO₂R⁶ where R⁶ has the same meaning as R⁴; an alkenyl group -CR⁷=CR⁸R⁹ where R⁷, R⁸ and R⁹, which may be the same or different, have the same meaning as R⁴; a cycloalkenyl group where n is an integer from 3 to 8; or a group where R¹⁰ and R¹¹ have the same meanings as R⁴ or together R¹⁰ and R¹¹ form a C₃ to C₇ alkylene group, and R¹² and R¹³, which may be the same or different, have the same meanings as R¹ and R², provided that R¹ and R² are not both hydrogen, the pharmaceutically acceptable salts, and mixtures thereof; and compounds and pharmaceutical composi­tions useful in practicing the method comprising the hypolipidemically active isoxazolidine-3,5-­dione compounds and a pharmaceutically acceptable carrier.

  一种控制哺乳动物高脂血症的方法，包括向哺乳动物施用有效量的具有降脂活性的化合物，该化合物的结构式如下： 其中R¹和R²可以相同或不同，条件是当R³是烯基或环烯基时，两者都不是氢，它们选自由下列组成的组：氢；1至18个碳原子的烷基；1至18个碳原子的取代烷基；1至18个碳原子的环烷基；4至18个碳原子的环烷基；4至18个碳原子的取代烷基；4至18个碳原子的环烷基；4 至 10 个环碳原子的环烷基；4 至 10 个环碳原子的取代环烷基；1 至 8 个碳原子的烷氧基；氨基；氨基甲酰基；酰氧基；烷氧基羰基；卤素、芳基和取代芳基，或 R¹ 和 R² 共同形成 C₃ 至 C₇ 亚烷基；以及 R³ 是氢；低级烷基；取代的低级烷基；环烷基；取代的环烷基；芳基；取代的芳基；基团 -COR⁴ 其中 R⁴ 是氢、低级烷基、取代的低级烷基、环烷基、取代的环烷基、芳基或取代的芳基；基团-CONHR⁵，其中 R⁵ 的含义与 R⁴ 相同； 烷氧羰基-CO₂R⁶，其中 R⁶ 的含义与 R⁴ 相同；烯基-CR⁷=CR⁸R⁹，其中 R⁷、R⁸ 和 R𠞙 可以相同或不同，其含义与 R⁴ 相同； 环烯基 其中 n 为 3 至 8 的整数；或一个基团 其中 R¹⁰ 和 R¹¹ 具有与 R⁴ 相同的含义，或者 R¹⁰ 和 R¹¹ 共同形成 C₃ 至 C₇ 亚烷基，并且 R¹² 和 R¹³ （可以相同或不同）具有与 R¹ 和 R² 相同的含义，前提是 R¹ 和 R² 不同时为氢、药学上可接受的盐、以及它们的混合物；以及用于实施本方法的化合物和药物组合物，包括具有降血脂活性的异噁唑烷-3,5-二酮化合物和药学上可接受的载体。
• ——
  作者：Tyrone Woodard、Manik L. Debnath、Rupendra Simlot、Robert A. Izydore、Dwayne L. Daniels、Oi T. Wong、Hamby ElSourady、Iris H. Hall

  DOI：10.1023/a:1016226317975

  日期：——

  A series of 2-benzoyl-4,4-dialkyl-3,5-isoxazolidinediones proved to have potent hypolipidemic activity, lowering both serum cholesterol and triglyceride levels at 10 or 20 mg/kg/day, IP and orally in rodents. 2-(3,4,5-Trimethoxybenzoyl)-4,4-diethyl-3,5-isoxazolidinedione (4) afforded the best hypolipidemic activity lowering normolipidemic CF1 mouse serum cholesterol levels 49% and serum triglyceride levels 34% at 20 mg/kg/day, IP. Compound 4 was selected as a typical derivative of the chemical class for further detailed studies. Serum cholesterol levels in normolipidemic Sprague Dawley male rats were reduced 45% after 8 weeks at 10 and 20 mg/kg/day of compound, orally. Serum triglyceride levels were reduced 38-49% at 10 and 20 mg/kg/day, orally. In vitro liver enzyme activities studies in normolipidemic CF1 mice showed the compound inhibited mitochondrial citrate exchange, acetyl CoA synthetase, HMG CoA reductase, acyl CoA cholesterol acyl transferase, acetyl CoA carboxylase, sn-glycerol-3-phosphate acyl transferase, phosphatidylate phosphohydrolase and heparin-induced lipoprotein lipase activities with increases in the activities of cholesterol ester hydrolase and ATP-dependent citrate lyase. Similar enzyme activities were inhibited in vivo except HMG CoA reductase activity was not inhibited in rat liver or small intestinal mucosa after 8 weeks drug administration. Cholesterol levels were reduced in tissues after 8 weeks administration of compound 4 in normolipidemic rats. Bile cholesterol and triglyceride levels were elevated after two weeks administration to rats at 20 mg/kg/day. Serum lipoprotein levels in normolipidemic and hyperlipidemic rats showed the cholesterol levels in VLDL and LDL fractions after 4, 6 and 8 weeks at 10 and 20 mg/kg/day were reduced whereas HDL-cholesterol levels were significantly elevated. Studies demonstrated that H-3-cholesterol and C-14-palmitic acid incorporation into lipids of the lipoprotein fraction was reduced by the drug but P-32-incorporation was generally elevated. The agent demonstrated no observable toxicity in rats after 8 weeks administration, orally. The acute toxicity study in normolipidemic mice at 20, 40 and 100 mg/kg/day, IP, demonstrated no observable harmful effects of the drug.
• IZYDORE, ROBERT A.;HALL, IRIS H.
  作者：IZYDORE, ROBERT A.、HALL, IRIS H.

  DOI：——

  日期：——
• US4946963A
  申请人：——

  公开号：US4946963A

  公开（公告）日：1990-08-07