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    Indole-,benzofuran-,and benzothiophene-containing lipoxygenase-inhibiting compounds
    1.
    发明授权
    Indole-,benzofuran-,and benzothiophene-containing lipoxygenase-inhibiting compounds 失效
    含吲哚，苯并呋喃和苯并噻吩的脂氧合酶抑制化合物

    公开(公告)号：US5250565A

    公开(公告)日：1993-10-05

    申请号：US823411

    申请日：1992-01-21

    申请人： Dee W. Brooks ,  James B. Summers

    发明人： Dee W. Brooks ,  James B. Summers

    IPC分类号： C07D209/14 ,  C07D307/81 ,  C07D333/58 ,  A61K31/38 ,  A61K31/34 ,  C07D209/04 ,  C07D333/52

    CPC分类号： C07D209/14 ,  C07D307/81 ,  C07D333/58

    摘要： Pro-drugs of potent 5-lipoxygenase inhibiting compounds comprise compounds of the formula ##STR1## in which A is an alkylene or alkenylene group, X is oxygen, sulfur, sulfoxyl, or substituted nitrogen, and Y is a group which includes substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic aryl. R.sup.1 is an alkyl, alkenyl, amino, alkylamino, dialkylamino, or hydroxyamino group or an amine group bearing a metabolically cleavable leaving group. M is hydrogen, a pharmaceutically acceptable cation or a metabolically cleavable leaving group, with the proviso that either M or R.sup.1 must bear a metabolically cleavable leaving group.

    摘要翻译： 有效的5-脂氧合酶抑制化合物的前药包括其中A为亚烷基或亚烯基的式（IMAGE）化合物，X为氧，硫，亚砜基或取代的氮，Y为包括取代或未取代的基团 碳环或取代或未取代的杂环芳基。 R 1是烷基，烯基，氨基，烷基氨基，二烷基氨基或羟基氨基或具有代谢可切割离去基团的胺基。 M是氢，药学上可接受的阳离子或代谢可切割的离去基团，条件是M或R 1必须承载代谢可切割的离去基团。

    Lipoxygenase inhibiting compounds
    2.
    发明授权
    Lipoxygenase inhibiting compounds 失效
    脂氧合酶抑制化合物

    公开(公告)号：US5026729A

    公开(公告)日：1991-06-25

    申请号：US430841

    申请日：1989-11-02

    申请人： Dee W. Brooks ,  James B. Summers ,  James H. Holms

    发明人： Dee W. Brooks ,  James B. Summers ,  James H. Holms

    IPC分类号： C07C275/64

    CPC分类号： C07C275/64

    摘要： Compounds having 5- and 12-lipoxygenase inhibitory activity have the structure ##STR1## where A is straight or branched divalent alkylene of from one to four carbon atoms, R.sub.1 is methyl, amino, or alkylamino of from one to six carbon atoms and the substituent group R.sub.2 is C.sub.1 -C.sub.2 alkyl.The group R.sub.3 is one or more substituents selected from hydrogen, alkyl of from one to six carbon atoms, alkoxy of from one to six carbon atoms, thioalkoxy of from one to six carbon atoms, halogen, cyano, and trihalomethyl, and R.sub.4 is one or more substituents selected from hydrogen, alkyl of from one to six carbon atoms, alkoxy of from one to six carbon atoms, thioalkoxy of from one to six carbon atoms, hydroxy, halogen, cyano, and trihalomethyl, with the proviso that when R.sub.1 is amino and A is >CHCH.sub.3, R.sub.3 and R.sub.4 may not both be hydrogen.The group designated M is hydrogen, a pharmaceutically acceptable cation, or a metabolically cleavable group. Pharmaceutical compositions and a method of inhibiting 5- and 12-lipoxygenase activity are also disclosed.

    摘要翻译： 具有5-和12-脂氧合酶抑制活性的化合物具有结构，其中A是1-4个碳原子的直链或支链二价亚烷基，R1是甲基，氨基或1-6个碳原子的烷基氨基， 基团R2是C1-C2烷基。 基团R3是一个或多个选自氢，一至六个碳原子的烷基，一个至六个碳原子的烷氧基，一个至六个碳原子的硫代烷氧基，卤素，氰基和三卤甲基的取代基，R4是一个 或更多取代基选自氢，一至六个碳原子的烷基，一至六个碳原子的烷氧基，一至六个碳原子的硫代烷氧基，羟基，卤素，氰基和三卤代甲基，条件是当R1为 氨基和A是> CHCH 3，R 3和R 4可以不都是氢。 指定为M的基团是氢，可药用阳离子或代谢可裂解基团。 还公开了药物组合物和抑制5-和12-脂肪氧合酶活性的方法。

    Indole, benzofuran, benzothiophene containing lipoxygenase inhibiting compounds
    3.
    发明授权
    Indole, benzofuran, benzothiophene containing lipoxygenase inhibiting compounds 失效
    吲哚，苯并呋喃，苯并噻吩含脂氧合酶抑制化合物

    公开(公告)号：US4873259A

    公开(公告)日：1989-10-10

    申请号：US138073

    申请日：1988-01-11

    申请人： James B. Summers, Jr. ,  Bruce P. Gunn ,  Dee W. Brooks

    发明人： James B. Summers, Jr. ,  Bruce P. Gunn ,  Dee W. Brooks

    IPC分类号： C07D209/14 ,  C07D307/81 ,  C07D333/58

    CPC分类号： C07D333/58 ,  C07D209/14 ,  C07D307/81

    摘要： Compounds of the formula: ##STR1## wherein R.sub.1 is (1) hydrogen, (2) C.sub.1 to C.sub.4 alkyl, (3) C.sub.2 to C.sub.4 alkenyl, or (4) NR.sub.2 R.sub.3, wherein R.sub.2 and R.sub.3 are independently selected from (1) hydrogen, (2) C.sub.1 to C.sub.4 alkyl and (3) hydroxyl, but R.sub.2 and R.sub.3 are not simultaneously hydroxyl;wherein X is oxygen, sulfur, SO.sub.2, or NR.sub.4, wherein R.sub.4 is (1) hydrogen, (2) C.sub.1 to C.sub.6 alkyl, (3) C.sub.1 to C.sub.6 alkoyl, (4) aroyl, or (5) alkylsulfonyl;A is selected from C.sub.1 to C.sub.6 alkylene and C.sub.2 to C.sub.6 alkenylene;n is 1-5;Y is selected independently at each occurrence from (1) hydrogen, (2) halogen, (3) hydroxy, (4) cyano, (5) halosubstituted alkyl, (6) C.sub.1 to C.sub.12 alkyl, (7) C.sub.2 to C.sub.12 alkenyl, (8) C.sub.1 to C.sub.12 alkoxy, (9) C.sub.3 to C.sub.8 cycloalkyl, (10) C.sub.1 -C.sub.8 thioalkyl, (11) aryl, (12) aryloxy, (13) aroyl, (14) C.sub.1 to C.sub.12 arylalkyl, (15) C.sub.2 to C.sub.12 arylalkenyl, (16) C.sub.1 to C.sub.12 arylalkoxy, (17) C.sub.1 to C.sub.12 arylthioalkoxy, and substituted derivatives of (18) aryl, (19) aryloxy, (20) aroyl, (21) C.sub.1 to C.sub.12 arylalkyl, (22) C.sub.2 to C.sub.12 arylalkenyl, (23) C.sub.1 to C.sub.12 arylalkoxy, or (24) C.sub.1 to C.sub.12 arylthioalkoxy, wherein substituents are selected from halo, nitro, cyano, C.sub.1 to C.sub.12 alkyl, alkoxy, and halosubstituted alkyl;Z is oxygen or sulfur;and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C.sub.1 to C.sub.12 alkoyl, are potent inhibitors of 5- and/or 12-lipoxygenase enzymes.Also disclosed are lipoxygenase inhibiting compositions and a method for inhibiting lipoxygenase activity.

    摘要翻译： 其中R 1是（1）氢，（2）C 1至C 4烷基，（3）C 2至C 4链烯基或（4）NR 2 R 3，其中R 2和R 3独立地选自（1）氢 ，（2）C1至C4烷基和（3）羟基，但R2和R3不同时为羟基; 其中X是氧，硫，SO 2或NR 4，其中R 4是（1）氢，（2）C 1至C 6烷基，（3）C 1至C 6烷酰基，（4）芳酰基或（5）烷基磺酰基; A选自C1至C6亚烷基和C2至C6亚烯基; n为1-5; 在（1）氢，（2）卤素，（3）羟基，（4）氰基，（5）卤代烷基，（6）C1至C12烷基，（7）C2至C12烯基， （8）C1至C12烷氧基，（9）C3至C8环烷基，（10）C1-C8硫代烷基，（11）芳基，（12）芳氧基，（13）芳酰基，（14）C1至C12芳烷基，（15） （18）芳基，（19）芳氧基，（20）芳酰基，（21）C1〜C12芳基烷基，（22）C1〜C12芳基烷氧基，（17）C1〜C12芳基烷氧基，（17） ）C 2至C 12芳基烯基，（23）C 1至C 12芳基烷氧基或（24）C 1至C 12芳硫基烷氧基，其中取代基选自卤素，硝基，氰基，C 1至C 12烷基，烷氧基和卤代烷基; Z是氧或硫; 和M是氢，可药用阳离子，芳酰基或C 1至C 12烷酰基，是5-和/或12-脂氧合酶的有效抑制剂。 还公开了脂氧合酶抑制组合物和抑制脂氧合酶活性的方法。

    Heteroaryl N-hydroxy amides and ureas with polar substituents as 5-lipoxygenase inhibitors
    8.
    发明授权
    Heteroaryl N-hydroxy amides and ureas with polar substituents as 5-lipoxygenase inhibitors 失效

    公开(公告)号：US4992464A

    公开(公告)日：1991-02-12

    申请号：US430710

    申请日：1989-11-01

    申请人： Dee W. Brooks ,  James B. Summers ,  Karen E. Rodriques ,  Robert G. Maki ,  Joseph F. Dellaria ,  James H. Holms ,  Jimmie L. Moore

    发明人： Dee W. Brooks ,  James B. Summers ,  Karen E. Rodriques ,  Robert G. Maki ,  Joseph F. Dellaria ,  James H. Holms ,  Jimmie L. Moore

    IPC分类号： C07D209/14 ,  C07D307/81 ,  C07D333/58 ,  A61K31/38 ,  C07D333/56

    CPC分类号： C07D333/58 ,  C07D209/14 ,  C07D307/81

    摘要： Compounds, compositions a method of inhibiting lipoxygenase and treating related disorders are disclosed. The compounds are of the formula:Ar-A(R.sub.2).sub.n -N(OM)-CZ-R.sub.1whereinAr is ##STR1## where X is O, S, SO.sub.2 or NR.sub.3 ;R.sub.3 is hydrogen, alkyl, alkylaryl, alkoyl, alkylakoyl, aroyl or alkylaroyl;Y is hydrogen, halogen, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, arylalkenyl, --OR, --SR, --COOR, --COR, --CON(R).sub.2, --OCOR, --N(R).sub.2, --O(CH).sub.2, --SO.sub.2 R, --SO.sub.2 N(R).sub.2, --O(CH.sub.2).sub.p OR, --CN, --NO.sub.2, --O(CH).sub.p O(CH.sub.2).sub.p OR or --CF.sub.3 ;R is hydrogen, hydroxyl, alkyl, alkylaryl or aryl;m is 0 to 5;p is 1 to 4;A is C.sub.1 -C.sub.12 alkylene or C.sub.2 -C.sub.14 alkenylene;R.sub.2 is --OR, --SR, --COOR, --COR, --CON(R).sub.2, --OCOR, --N(R).sub.2, --O(CH.sub.2).sub.y CON(R).sub.2, --O(CH.sub.2).sup.y OR, --CN, --NO.sub.2, 1-tetrazolo, C.sub.4 -C.sub.8 cyclic amido, imidazolo, --O(CH.sub.2).sub.y O(CH.sub.2).sub.y OR, --CF.sub.3, --N(R) COCHR--NH(R), CONHCH(R)CO.sub.2 R, --OCOCHR-NH(R), --CR(NHR)CONR, --CR(NHR)COR, morpholino, --NH(CH.sub.2).sub.y OH, --N[(CH.sub.2).sub.y OH].sub.2, --N.sub.3, --SO.sub.2 N(R).sub.2, --N(R)COR, --N(R)COOR, --N(R)CON(R).sub.2, --C(.dbd.NOH)NHOH or --C(.dbd.NOH)NH.sub.2 where R is as defined above, y is 1 to 4 and --N(R).sub.2 can form a heterocyclic ring of 5-8 atoms;M is hydrogen, a pharmaceutically acceptable cation or a metabolically cleavable group;Z is oxygen or sulfur; andR.sub.1 us hydrogen, alkyl, alkenyl, --NR.sub.4 R.sub.5, --NCOR.sub.6 or --Q--(R.sub.2).sub.2 where R.sub.4 and R.sub.5 independently selected from the group consisting of hydrogen, hydroxyl, alkyl, substituted alkyl with 1-3 substituents selected from the group consisting of R.sub.2 as defined above, acyl, aryl and CON(R).sub.2 is as defined above, R.sub.6 is hydrogen alkyl, alkylaryl, aryl or NR.sub.4 R.sub.5 where R.sub.4 and R.sub.5 are as defined above and where NR.sub.4 R.sub.5 can form a heterocyclic ring of a 5-8 atoms, Q is alkyl, alkenyl or aryl and z is 0 to 3; provided when n is O, R.sub.1 is not hydrogen, alkyl, alkenyl, or NR.sub.4 R.sub.5 wherein R.sub.4 and R.sub.5 are as defined above; and the pharmaceutically acceptable salts thereof.

    Arylalkylether and arylalkylthioether inhibitors of lipoxygenase enzyme activity
    9.
    发明授权
    Arylalkylether and arylalkylthioether inhibitors of lipoxygenase enzyme activity 失效
    芳基烷基醚和芳烷基硫醚抑制剂的脂氧合酶活性

    公开(公告)号：US5183818A

    公开(公告)日：1993-02-02

    申请号：US750362

    申请日：1991-08-27

    申请人： Dee W. Brooks ,  Andrew O. Stewart ,  Jonathan G. Martin

    发明人： Dee W. Brooks ,  Andrew O. Stewart ,  Jonathan G. Martin

    IPC分类号： C07D307/38 ,  C07D307/42 ,  C07D333/16 ,  C07D333/34 ,  C07D333/56 ,  C07D495/04

    CPC分类号： C07D307/42 ,  C07D307/38 ,  C07D333/16 ,  C07D333/34 ,  C07D333/56 ,  C07D495/04

    摘要： The present invention provides compounds having the structureY-Het-[Q.sub.1 ]-X-[Q.sub.2 ]-Zwhich inhibit the catalytic action of lipoxygenase enzymes, particularly 5-lipoxygenase, and thereby reduce the biosynthesis of leukotrienes B.sub.4, C.sub.4, D.sub.4, and E.sub.4.In the generic formula given above, X is oxygen or sulfur and Het is a heteroaryl group selected from the group consisting of furyl, thienyl, 2-, 3-, and 4-pyridyl, 2- and 3-benzo[b]furyl, 2- and 3-benzo[b]thienyl and thienothienyl.Y is one or two substituents independently selected from hydrogen, hydroxy, halogen, cyano, alkyl, haloalkyl, alkoxy, alkylthio, alkoxyaryl), alkylthioaryl, arylalkoxy, arylalkylthio, aryloxy, arylthio, alkylamido, cycloalkyl, alkanoyl, alkoxycarbonyl, amino, alkylamino, dialkylamino, and the following groups wherein R, at each occurrence, is independently selected from hydrogen and alkyl of from one to six carbon atoms: --CRROR, --NRC(O)R, --NRC(O)OR, and --C(O)NRR.The group Q.sub.1 is absent or is divalent alkylene of from one to six carbon atoms, and Q.sub.2 is divalent alkylene from from two to ten carbon atoms.The group Z is N(OR.sub.1)COR.sub.2 where R.sub.1 is selected from hydrogen or a pharmaceutically suitable salt. R.sub.2 is selected from hydrogen; alkyl; cycloalkyl; amino; alkylamino, optionally substituted by hydroxyl, halogen, alkoxy or carboxyl; dialkylamino in which the alkyl groups are independently are optionally substituted by hydroxyl, halogen, alkoxy or carboxyl; cycloalkylamino; 2-hydroxyethylamino; N-morpholino; N-thiomorpholino; N-piperazine; N'-alkyl-N-piperazine and cyclopropylmethylamino.

    摘要翻译： 本发明提供具有抑制脂氧合酶，特别是5-脂氧合酶的催化作用的结构为Y-Het- [Q1] -X- [Q2] -Z的化合物，从而减少白三烯B4，C4，D4的生物合成， 和E4。 在上述通式中，X是氧或硫，Het是选自呋喃基，噻吩基，2-，3-和4-吡啶基，2-和3-苯并[b]呋喃基的杂芳基， 2-和3-苯并[b]噻吩基和噻吩并噻吩基。 Y是一个或两个独立地选自氢，羟基，卤素，氰基，烷基，卤代烷基，烷氧基，烷硫基，烷氧基芳基），烷基硫代芳基，芳基烷氧基，芳基烷硫基，芳氧基，芳硫基，烷基酰氨基，环烷基，烷酰基，烷氧基羰基，氨基，烷基氨基， 二烷基氨基和下列基团，其中R 1在每次出现时独立地选自氢和1至6个碳原子的烷基：-CRROR，-NRC（O）R，-NRC（O）OR和-C（O ）NRR。 基团Q1不存在或为1至6个碳原子的二价亚烷基，Q 2为2至10个碳原子的二价亚烷基。 基团Z是N（OR 1）COR 2，其中R 1选自氢或药学上合适的盐。 R2选自氢; 烷基; 环烷基 氨基; 任选被羟基，卤素，烷氧基或羧基取代的烷基氨基; 其中烷基独立的二烷基氨基任选被羟基，卤素，烷氧基或羧基取代; 环烷基氨基; 2-羟基乙基氨基; N-吗啉代; N-硫代吗啉代 N-哌嗪; N'-烷基-N-哌嗪和环丙基甲基氨基。