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    Lipoxygenase and cyclooxygenase inhibiting compounds
    25.
    发明授权
    Lipoxygenase and cyclooxygenase inhibiting compounds 失效
    脂氧合酶和环加氧酶抑制化合物

    公开(公告)号：US5516789A

    公开(公告)日：1996-05-14

    申请号：US421125

    申请日：1995-04-12

    申请人： Clint D. W. Brooks ,  Andrew O. Stewart ,  Anwer Basha ,  Randy L. Bell

    发明人： Clint D. W. Brooks ,  Andrew O. Stewart ,  Anwer Basha ,  Randy L. Bell

    IPC分类号： C07C275/64 ,  C07D307/52 ,  C07D333/20 ,  C07D333/58 ,  C07D409/12 ,  A61K31/405 ,  C07D209/14

    CPC分类号： C07D409/12 ,  C07C275/64 ,  C07D307/52 ,  C07D333/20 ,  C07D333/58

    摘要： Compounds having the structure ##STR1## or a pharmaceutically acceptable salt thereof have activity as inhibitors of cylooxygenase and 5-lipoxygenase, reduce the biosynthesis of leukotrienes B.sub.4, C.sub.4, D.sub.4, and E.sub.4 and cylooxygenase products such as prostaglandins and thromboxane and are useful in the treatment of inflammatory and allergic disease states. The compounds have the structure indicated above wherein A is selected from (a) optinally substituted carbocyclic aryl, (b) optinally substituted furyl, (c) optinally substituted benzo[b]furyl, (d) optinally substituted thienyl, (e) optinally substituted pyridyloxy, (f) optinally substituted pyridylalkyl, (g) optinally substituted benzo[b]thienyl, (h) optinally substituted pyridyl, (i) optinally substituted quinolyl, and (j) optinally substituted indolyl; X is selected from (a) optionally substituted alkyl, (b) optinally substituted alkenyl, and (c) optinally substituted alkynyl; R.sup.1 and R.sup.2 are independently selected from hydrogen, hydroxy, and alkyl; and Z is a residue of a non-steroidal anti-inflammatory drug of the general formula Z--COOH.

    摘要翻译： 具有结构或其药学上可接受的盐的化合物具有作为环氧合酶和5-脂氧合酶抑制剂的活性，降低白细胞三烯B4，C4，D4和E4以及环加氧酶产物如前列腺素和血栓烷的生物合成，并且可用于 治疗炎症和过敏性疾病状态。 化合物具有上述结构，其中A选自（a）光学取代的碳环芳基，（b）光取代的呋喃基，（c）光取代的苯并[b]呋喃基，（d）最佳取代的噻吩基，（e） 吡啶基氧基，（f）选择性取代的吡啶基烷基，（g）最佳取代的苯并[b]噻吩基，（h）最佳取代的吡啶基，（i）最佳取代的喹啉基和（j） X选自（a）任选取代的烷基，（b）光学取代的烯基和（c）最佳取代的炔基; R 1和R 2独立地选自氢，羟基和烷基; Z为通式Z-COOH的非甾体抗炎药物的残基。

    ((4-alkoxypyran-4-yl) substituted) ether, arylalkyl-, arylalkenyl-, and arylalkynyl)urea inhibitors of 5-lipoxygenase
    26.
    发明授权
    ((4-alkoxypyran-4-yl) substituted) ether, arylalkyl-, arylalkenyl-, and arylalkynyl)urea inhibitors of 5-lipoxygenase 失效
    （（4-烷氧基吡喃-4-基）取代的）醚，芳基烷基 - ，芳基烯基 - 和芳基炔基）尿素抑制剂5-脂氧合酶

    公开(公告)号：US5446062A

    公开(公告)日：1995-08-29

    申请号：US152569

    申请日：1993-11-12

    申请人： Joseph F. Dellaria ,  Anwer Basha ,  Lawrence A. Black ,  Linda J. Chernesky ,  Wendy Lee

    发明人： Joseph F. Dellaria ,  Anwer Basha ,  Lawrence A. Black ,  Linda J. Chernesky ,  Wendy Lee

    IPC分类号： C07D309/10 ,  C07D405/12 ,  A61K31/35 ,  C07D405/10

    CPC分类号： C07D405/12 ,  C07D309/10

    摘要： Compounds of the structure ##STR1## where W is selected from ##STR2## where Q is oxygen or sulfur, R.sup.6 and R.sup.7 are hydrogen or alkyl, or R.sup.6 and R.sup.7, together with the nitrogen atoms to which they are attached, define a radical of formula ##STR3## Z is --CH.sub.2 --, oxygen, sulfur, or --NR.sup.9, L.sup.1 and L.sup.2 are selected from a valence bond, alkylene, propenylene, and propynylene; R.sup.1 and R.sup.2 are independently selected from alkyl, alkoxy, haloalkyl, halogen, cyano, amino, alkoxycarbonyl, and dialkylaminocarbonyl; Y is selected from oxygen, >NR.sup.10, and ##STR4## L.sup.3 is selected from alkylene of one to three carbon atoms, propenylene, propynylene, ##STR5## and R.sup.3, R.sup.4, and R.sup.5 are hydrogen or alkyl of one to four carbon atoms inhibit the synthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

    摘要翻译： 其中W选自的结构的化合物，其中Q是氧或硫，R6和R7是氢或烷基，或R6和R7与它们所连接的氮原子一起定义为 式Z是-CH 2 - ，氧，硫或-NR 9，L 1和L 2选自价键，亚烷基，亚丙烯基和亚丙炔基; R 1和R 2独立地选自烷基，烷氧基，卤代烷基，卤素，氰基，氨基，烷氧基羰基和二烷基氨基羰基; Y选自氧，> NR10，并且 L3选自1至3个碳原子的亚烷基，亚丙烯基，亚丙炔基，R 3，R 4和R 5是氢或1-4个碳原子的烷基抑制 白三烯的合成。 这些化合物可用于治疗或改善过敏性和炎性疾病状态。

    [Alkoxy-, alkenyloxy-, alkynyloxy-, and phenylmethyloxyalkoxycycloalkyl or alkoxycycloheteroalkyl]naphtho[2,3-c]furan-1(3H)-one inhibitors of 5-lipoxygenase
    27.
    发明授权
    [Alkoxy-, alkenyloxy-, alkynyloxy-, and phenylmethyloxyalkoxycycloalkyl or alkoxycycloheteroalkyl]naphtho[2,3-c]furan-1(3H)-one inhibitors of 5-lipoxygenase 失效
    烷氧基 - ，烯氧基 - ，炔氧基 - 和苯基甲氧基烷氧基环烷基或烷氧基环杂烷基]萘并[2,3-c]呋喃-1（3H） - 酮抑制剂5-脂氧合酶

    公开(公告)号：US5426111A

    公开(公告)日：1995-06-20

    申请号：US344774

    申请日：1994-11-23

    申请人： Joseph F. Dellaria ,  James D. Ratajczyk ,  Clint D. W. Brooks ,  Anwer Basha

    发明人： Joseph F. Dellaria ,  James D. Ratajczyk ,  Clint D. W. Brooks ,  Anwer Basha

    IPC分类号： C07C65/26 ,  C07D307/92 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D407/14 ,  C07D409/04 ,  C07D409/14 ,  A61K31/435 ,  C07C63/64 ,  C07D315/00 ,  C07D409/00

    CPC分类号： C07D307/92 ,  C07C65/26 ,  C07D405/04 ,  C07D405/14 ,  C07D407/12 ,  C07D407/14 ,  C07D409/04 ,  C07D409/14

    摘要： Compounds of formula ##STR1## Ar is selected from (a) phenyl, (b) phenyl substituted with one or more groups selected from halogen, cyano, alkyl, haloalkyl, alkoxy, and alkoxycarbonyl, (c) furyl, (d) furyl substituted with one or more groups selected from halogen, alkyl, and alkoxy, (e) pyridyl, (f) pyridyl substituted with one or more groups selected from halogen, alkyl, and alkoxy, (g) thienyl, and (h) thienyl substituted with one or more groups selected from halogen, alkyl, and alkoxy; L is selected from alkylene of one to three carbon atoms, alkenylene of two to three carbon atoms, and alkynylene of two to three carbon atoms, and ##STR2## wherein p is an integer of 1 to 4, inclusive, and R.sup.4 is selected from the group consisting of hydrogen, alkyl of one to four carbon atoms, halogen, haloalkyl of one to four carbon atoms, and alkoxy of one to six carbon atoms;R.sup.1 is alkyl; R.sup.2 is hydrogen or alkyl; m is 1 or 2; Z is oxygen or CHOR.sup.3, and n is 0 or 1 are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

    摘要翻译： 式（Ia）化合物选自（a）苯基，（b）被一个或多个选自卤素，氰基，烷基，卤代烷基，烷氧基和烷氧基羰基的基团取代的苯基，（c）呋喃基，（d （f）吡啶基，（f）被一个或多个选自卤素，烷基和烷氧基的基团取代的吡啶基，（g）噻吩基，和（h）被卤素，烷基和烷氧基取代的吡啶基， 被一个或多个选自卤素，烷基和烷氧基的基团取代的噻吩基; L选自1至3个碳原子的亚烷基，2至3个碳原子的亚烯基和2至3个碳原子的亚炔基，和其中p是1至4的整数，并且R 4选自 由氢，1-4个碳原子的烷基，卤素，1-4个碳原子的卤代烷基和1至6个碳原子的烷氧基组成的组; R1是烷基; R2是氢或烷基; m为1或2; Z是氧或CHOR3，n是0或1是脂氧合酶的有效抑制剂，从而抑制白细胞三烯的生物合成。 这些化合物可用于治疗或改善过敏性和炎性疾病状态。

    Pyrimido-pyrimidine lipoxygenase inhibiting compounds
    29.
    发明授权
    Pyrimido-pyrimidine lipoxygenase inhibiting compounds 失效
    嘧啶 - 嘧啶脂氧合酶抑制化合物

    公开(公告)号：US4963541A

    公开(公告)日：1990-10-16

    申请号：US314008

    申请日：1989-02-22

    申请人： Dee W. Brooks ,  Anwer Basha

    发明人： Dee W. Brooks ,  Anwer Basha

    IPC分类号： C07D487/04

    CPC分类号： C07D487/04

    摘要： Compounds of the formula: ##STR1## wherein A is selected from NR.sub.1 R.sub.2 and N(OR.sub.6)R.sub.2 ; and B and C are chloro when A is N(OR.sub.6)R.sub.2 or are independently selected from NHR.sub.3 and NR.sub.4 R.sub.5 where R.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5 are independently selected from the group consisting of alkyl, cycloalkyl and alkylaryl each of which may be unsubstituted or substituted with one or more substituents selected from the group consisting of hydroxy, OR, NRR, OCOR, OCONRR, NRCOR and NRCONRR where R is selected from the group consisting of hydrogen, alkyl, aryl, alkylaryl, alkoxy and hydroxy or R.sub.1 and R.sub.2 or R.sub.4 and R.sub.5 together can form a heteroaryl group and R.sub.6 is a member selected from the group consisting of hydrogen, alkyl, alkylaryl and trialkylsilyl; and the pharmaceutically acceptable salts thereof.These compounds are useful as inhibitors of lipoxygenase enzymes.

    摘要翻译： 下式的化合物：其中A选自NR1R2和N（OR6）R2; 当A为N（OR 6）R 2时，B和C为氯，或独立地选自NHR 3和NR 4 R 5，其中R 1，R 2，R 3，R 4和R 5独立地选自烷基，环烷基和烷芳基，其各自可以是 未取代或被一个或多个选自羟基，OR，NRR，OCOR，OCONRR，NRCOR和NRCONRR的取代基取代，其中R选自氢，烷基，芳基，烷基芳基，烷氧基和羟基或R 1和 R2或R4和R5一起可以形成杂芳基，R6是选自氢，烷基，烷基芳基和三烷基甲硅烷基的成员; 及其药学上可接受的盐。 这些化合物可用作脂氧合酶的抑制剂。