公开(公告)号：US5512581A

公开(公告)日：1996-04-30

申请号：US432491

申请日：1995-05-01

申请人： Dee W. Brooks ,  Pramila Bhatia ,  Teodozyi Kolasa

发明人： Dee W. Brooks ,  Pramila Bhatia ,  Teodozyi Kolasa

IPC分类号： A61K31/426 ,  A61K31/428 ,  A61K31/437 ,  A61K31/4406 ,  A61K31/4409 ,  A61K31/4433 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/498 ,  A61K31/505 ,  A61P11/00 ,  A61P11/06 ,  A61P17/06 ,  A61P19/02 ,  A61P19/06 ,  A61P27/14 ,  A61P43/00 ,  C07D213/30 ,  C07D215/14 ,  C07D215/22 ,  C07D215/227 ,  C07D215/36 ,  C07D235/12 ,  C07D239/26 ,  C07D241/42 ,  C07D263/56 ,  C07D277/24 ,  C07D277/64 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D513/04 ,  C07D215/12

CPC分类号： C07D213/30 ,  C07D215/14 ,  C07D215/227 ,  C07D215/36 ,  C07D235/12 ,  C07D239/26 ,  C07D241/42 ,  C07D263/56 ,  C07D277/24 ,  C07D277/64 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/12 ,  C07D513/04

摘要： The present invention relates to a compound of formulaW--X--Q--Y--CH(R.sup.1)--O--N.dbd.C(R.sup.2)--A--COMor a pharmaceutically acceptable salt thereof wherein W is optionally substituted aryl or heteroaryl; X is a valence bond, or methylene, divalent alkylene, alkenylene, alkynylene or alkyloxy; Q is a valence bond, or --O--, --S--, >NR.sup.4 or >NCOR.sup.5 ; Y is optionally substituted phenyl, biphenyl, naphthyl, tetrahydronaphthyl, indolyl, pyridyl, or benzo b!thienyl, thienyl, thiazolyl, or thiazolylphenyl; R.sup.1 is alkyl, cycloalkyl, alkoxyalkyl, aryl or arylalkyl, heteroaryl or heteroarylalkyl; R.sup.2 is hydrogen, alkyl or hydroxyalkyl; A is a valence bond or is selected from alkylene, alkenylene, alkynylene, cycloalkylene, phenylene, pyridylene, thienylene and furylene; and M is a pharmaceutically acceptable, metabolically cleavable group, --OR.sup.6, --NR.sup.6 R.sup.7, --NH-tetrazoyl, --NH-2-, 3-, or 4-pyridyl, and --NH-2-, 4-, or 5-thiazolyl which inhibit leukotriene biosynthesis and are useful in the treatment of inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method for inhibiting lipoxygenase activity and leukotriene biosynthesis.

摘要翻译： 本发明涉及式W-X-Q-Y-CH（R 1）-O-N = C（R 2）-A-COM的化合物或其药学上可接受的盐，其中W为任选取代的芳基或杂芳基; X是价键，或亚甲基，二价亚烷基，亚烯基，亚炔基或烷氧基; Q是价键，或-O-，-S-，> NR4或> NCOR5; Y是任选取代的苯基，联苯基，萘基，四氢萘基，吲哚基，吡啶基或苯并[b]噻吩基，噻吩基，噻唑基或噻唑基苯基; R 1是烷基，环烷基，烷氧基烷基，芳基或芳基烷基，杂芳基或杂芳基烷基; R2是氢，烷基或羟烷基; A是价键或选自亚烷基，亚烯基，亚炔基，亚环烷基，亚苯基，亚吡啶基，亚噻吩基和亚芳基; 并且M是药学上可接受的代谢可裂解基团-OR 6，-NR 6 R 7，-NH-四唑基，-NH-2-，3-或4-吡啶基和-NH-2-，4-或5-噻唑基 其抑制白细胞三烯生物合成并且可用于治疗炎性疾病状态。 还公开了白三烯生物合成抑制组合物和抑制脂氧合酶活性和白三烯生物合成的方法。

公开(公告)号：US5399699A

公开(公告)日：1995-03-21

申请号：US186410

申请日：1994-01-24

申请人： Teodozyi Kolasa ,  Pramila Bhatia ,  Dee W. Brooks

发明人： Teodozyi Kolasa ,  Pramila Bhatia ,  Dee W. Brooks

IPC分类号： C07D401/12 ,  C07D417/12 ,  C07D401/02 ,  A61K31/425 ,  A61K31/47 ,  C07D417/02

CPC分类号： C07D401/12 ,  C07D417/12

摘要： Compounds of the structure ##STR1## where A.sub.1 is alkylene or cycloalkylene; A.sub.2 is a valence bond, alkylene, or cycloalkylene; R.sub.1 is selected from hydrogen, alkylthio, optionally substituted phenylthio, optionally substituted phenylalkylthio, optionally substituted 2-, 3- and 4-pyridylthio, optionally substituted 2- and 3-thienylthio, and optionally substituted 2-thiazolylthio; R.sup.2 is selected from optionally substituted phenylalkyl and optionally substituted heteroarylakyl; R.sup.3 is selected from alkyl, alkoxy, optionally substituted phenyl, optionally substituted phenoxy, optionally substituted phenylalkyl, optionally substituted phenylalkoxy, optionally substituted naphthyl,optionally substituted naphthyloxy, optionally substituted naphthylalkyl, optionally substituted naphthylalkoxy, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy; R.sup.4 is selected from hydrogen and optionally substituted alkyl; and Z is selected from --COOB, --C(OB)R.sup.6 R.sup.6, --COOalkyl, --COOalkylaryl, --CONR.sup.5 R.sup.6, and --COR.sup.6 are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment of amelioration of allergic and inflammatory disease states.

摘要翻译： 其中A1是亚烷基或亚环烷基的结构的化合物; A2是价键，亚烷基或亚环烷基; R 1选自氢，烷硫基，任选取代的苯硫基，任选取代的苯基烷硫基，任选取代的2-，3-和4-吡啶硫基，任选取代的2-和3-噻吩硫基，以及任选取代的2-噻唑基硫基; R2选自任选取代的苯基烷基和任选取代的杂芳基; R 3选自烷基，烷氧基，任选取代的苯基，任选取代的苯氧基，任选取代的苯基烷基，任选取代的苯基烷氧基，任选取代的萘基，任选取代的萘基氧基，任选取代的萘基烷基，任选取代的萘基烷氧基，任选取代的杂芳基，任选取代的杂芳氧基， 杂芳基烷基和任选取代的杂芳基烷氧基; R4选自氢和任选取代的烷基; 并且Z选自-COOB，-C（OB）R 6 R 6，-COO烷基，-COO烷基芳基，-CONR 5 R 6和-COR 6是脂氧合酶的有效抑制剂，因此抑制白细胞三烯的生物合成。 这些化合物可用于治疗改善变态反应和炎性疾病状态。