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    • 65. 发明授权
    • 2,4-pentadienoic acid derivatives having retinoid-like biological
activity
    • 具有类视黄醇样生物活性的2,4-戊二烯酸衍生物
    • US5663367A
    • 1997-09-02
    • US656137
    • 1996-05-31
    • Vidyasagar VuligondaRoshantha A. Chandraratna
    • Vidyasagar VuligondaRoshantha A. Chandraratna
    • A61K31/35A61K31/20A61K31/23A61K31/38A61K31/47A61P17/00A61P43/00C07C57/50C07C69/618C07C215/02C07C215/18C07C311/58C07C335/06C07C403/00C07D277/22C07D311/58C07D333/54C07D335/06C07D333/12C07D307/40C07D307/56C07D333/22
    • C07D333/54A61K31/20A61K31/23C07C57/50C07C69/618C07D311/58C07D335/06
    • Compounds of Formula 1 ##STR1## wherein Z is selected from the group consisting of the radicals shown in Formula 2 and in Formula 3, ##STR2## Y is cycloalkyl or cycloalkenyl of 3 to 8 carbons optionally substituted with one or two R.sub.4 groups, or Y is selected from phenyl, pyridyl, thienyl, furyl, pyrrolyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, oxazolyl, and imidazolyl, said groups being optionally substituted with one or two R.sub.4 groups, the divalent Y radical being substituted by the Z and --CR.sub.1 .dbd.CR.sub.1 --CR.sub.1 .dbd.CR.sub.1 groups on adjacent carbons; X is S, O, or NR.sub.5 ; n is 1 or 2; R.sub.1 and R.sub.2 independently are H, lower alkyl or fluoroalkyl; R.sub.3 is hydrogen, lower alkyl, Cl or Br; R.sub.4 is lower alkyl, fluoroalkyl or halogen; R.sub.5 is H or lower alkyl, and B is hydrogen, COOH or a pharmaceutically acceptable salt thereof, COOR.sub.8, CONR.sub.9 R.sub.10, --CH.sub.2 OH, CH.sub.2 OR.sub.11, CH.sub.2 OCOR.sub.11, CHO, CH(OR.sub.12).sub.2, CHOR.sub.13 O, --COR.sub.7, CR.sub.7 (OR.sub.12).sub.2, CR.sub.7 OR.sub.13 O, or tri-lower alkylsilyl, where R.sub.7 is an alkyl, cycloalkyl or alkenyl group containing 1 to 5 carbons, R.sub.8 is an alkyl group of 1 to 10 carbons, a cycloalkyl group of 5 to 10 carbons or trimethylsilylalkyl where the alkyl group has 1 to 10 carbons, or R.sub.8 is phenyl or lower alkylphenyl, R.sub.9 and R.sub.10 independently are hydrogen, an alkyl group of 1 to 10 carbons, or a cycloalkyl group of 5-10 carbons, or phenyl or lower alkylphenyl, R.sub.11 is lower alkyl, phenyl or lower alkylphenyl, R.sub.12 is lower alkyl, and R.sub.13 is divalent alkyl radical of 2-5 carbons, have retinoid like biological activity.
    • 式1的化合物其中Z选自由式2和式3所示的基团组成的组。式3 Y是3至8个碳的环烷基或环烯基,任选地 被一个或两个R 4基取代,或Y选自苯基,吡啶基,噻吩基,呋喃基,吡咯基,哒嗪基,嘧啶基,吡嗪基,噻唑基,恶唑基和咪唑基,所述基团任选被一个或两个R 4基团取代,二价 Y基团被相邻碳上的Z和-CR1 = CR1-CR1 = CR1基团取代; X是S,O或NR5; n为1或2; R1和R2独立地为H,低级烷基或氟代烷基; R3是氢,低级烷基,Cl或Br; R4是低级烷基,氟烷基或卤素; R 5是H或低级烷基,B是氢,COOH或其药学上可接受的盐,COOR8,CONR9R10,-CH2OH,CH2OR11,CH2OCOR11,CHO,CH(OR12)2,CHOR13O,-COR7,CR7(OR12) CR 7OR 13 O或三低级烷基甲硅烷基,其中R 7为含有1至5个碳的烷基,环烷基或烯基,R 8为碳原子数1至10的烷基,碳原子数为5至10的环烷基或烷基具有的三甲基甲硅烷基烷基 1至10个碳,或R8为苯基或低级烷基苯基,R9和R10独立地为氢,1-10个碳原子的烷基或5-10个碳原子的环烷基,或苯基或低级烷基苯基,R11为低级烷基, 苯基或低级烷基苯基,R12为低级烷基,R13为2-5个碳原子的二价烷基,具有类视黄醇类生物活性。