Abstract:
The present invention relates to a compound of the formula: W-X-Q-Y-CH(R )-O-N=C(R )-A-COM, or 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 or > NCOR ; Y is optionally substituted phenyl, biphenyl, naphthyl, tetrahydronaphthyl, indolyl, pyridyl, or benzo[b]thienyl, thienyl, thiazolyl, or thiazolylphenyl; R is alkyl, cycloalkyl, alkoxyalkyl, aryl or arylalkyl, heteroaryl or heteroarylalkyl; R 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 , -NR R , -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.
Abstract translation:本发明涉及下式化合物:W-X-Q-Y-CH(R 1)-O-N = C(R 2)-A-COM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-,> NR 4或NCOR 5。 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; R 2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-三唑基,-NH-2-,3-或4-吡啶基和-NH- 抑制白细胞三烯生物合成的2-,4-或5-噻唑基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。
Abstract:
Compounds having formula (I) or a pharmaceutically acceptable salt thereof wherein W is selected from the group consisting of optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; R and R are one or more groups independently selected from hydrogen, alkyl, haloalkyl, alkoxy, and halogen; Z is selected from the group consisting of N-OH, N-O-A-COM, CH-COM, and CH-CH=N-O-A-COM wherein A is selected from the group consisting of alkylene, alkenylene, cycloalkylene, and optionally substituted alkylphenyl wherein the alkyl portion is of one to six carbon atoms, and M is selected from the group consisting of a pharmaceutically acceptable, metabolically cleavable group, -OR , and -NR R , inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis.
Abstract translation:具有式(I)化合物或其药学上可接受的盐,其中W选自任选取代的喹啉基,任选取代的苯并噻唑基,任选取代的苯并恶唑基,任选取代的苯并咪唑基,任选取代的喹喔啉基,任选取代的吡啶基,任选取代的嘧啶基,和 任选取代的噻唑基; R 1和R 2是一个或多个独立地选自氢,烷基,卤代烷基,烷氧基和卤素的基团; Z选自N-OH,NOA-COM,CH-COM和CH-CH = NOA-COM,其中A选自亚烷基,亚烯基,亚环烷基和任选取代的烷基苯基,其中烷基 部分为1至6个碳原子,M选自药学上可接受的,代谢可裂解基团-OR 3和-NR 4 R 5,抑制白三烯生物合成,并且可用于 治疗过敏和炎症疾病状态。 还公开了白三烯生物合成抑制组合物和抑制白三烯生物合成的方法。
Abstract:
Compounds having formula (I) or a pharmaceutically acceptable salt thereof wherein W and Y at each occurrence are the same and W is selected from the group consisting of optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; Y is selected from optionally substituted phenylene and optionally substituted (c) wherein the alkylene portion is of one to six carbon atoms; A is selected from alkylene, alkenylene, cycloalkylene, and optionally substituted (d) wherein the alkylene portion is of one to six carbon atoms: and M is selected from hydrogen, a pharmaceutically acceptable cation, a metabolically cleavable group, -OR , and -NR R , inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis in a mammal.
Abstract:
Compounds having formula (I), wherein W is the same at each occurrence and is selected from optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; R and R are independently selected from hydrogen, alkyl, haloalkyl, alkoxy, halogen; R is a valence bond or is selected from hydrogen and alkyl; X is a valence bond or is selected from alkylene, alkenylen, and alkynylene; and Z is selected from (a) COM, (b) CH=N-O-A-COM, (c) CH2-O-N=A-COM wherein A is selected from alkylene and cycloalkylene, and M is selected from (a) a pharmaceutically acceptable metabolically cleavable group, (b) -OR , (c) -NR R , (d) -NR SO2R , (e) -NH-Tetrazolyl, and (f) glycinyl inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis.
Abstract translation:具有式(I)的化合物,其中W在每次出现时相同,并且选自任选取代的喹啉基,任选取代的苯并噻唑基,任选取代的苯并恶唑基,任选取代的苯并咪唑基,任选取代的喹喔啉基,任选取代的吡啶基,任选取代的嘧啶基, 噻唑基; R 1和R 2独立地选自氢,烷基,卤代烷基,烷氧基,卤素; R 3是价键或选自氢和烷基; X是价键或选自亚烷基,烯基和亚炔基; 并且Z选自(a)COM,(b)CH = NOA-COM,(c)CH2-ON = A-COM其中A选自亚烷基和亚环烷基,M选自(a)药学上可接受的代谢 可裂解基团,(b)-OR 6,(c)-NR 7 R 8,(d)-NR 6 SO 2 R 9,(e)-NH-四唑基和(f) 甘氨酰抑制白三烯生物合成,可用于治疗过敏性和炎性疾病状态。 还公开了白三烯生物合成抑制组合物和抑制白三烯生物合成的方法。
Abstract:
Compounds having formula (I), wherein W is the same at each occurrence and is selected from optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; R?1 and R2¿ are independently selected from hydrogen, alkyl, haloalkyl, alkoxy, halogen; R3 is a valence bond or is selected from hydrogen and alkyl; X is a valence bond or is selected from alkylene, alkenylen, and alkynylene; and Z is selected from (a) COM, (b) CH=N-O-A-COM, (c) CH¿2?-O-N=A-COM wherein A is selected from alkylene and cycloalkylene, and M is selected from (a) a pharmaceutically acceptable metabolically cleavable group, (b) -OR?6¿, (c) -NR7R8, (d) -NR6SO2R9, (e) -NH-Tetrazolyl, and (f) glycinyl inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis.
Abstract:
The present invention relates to a compound of the formula: W-X-Q-Y-CH(R1)-O-N=C(R2)-A-COM, or 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-, > NR4 or > NCOR5; Y is optionally substituted phenyl, biphenyl, naphthyl, tetrahydronaphthyl, indolyl, pyridyl, or benzo[b]thienyl, thienyl, thiazolyl, or thiazolylphenyl; R1 is alkyl, cycloalkyl, alkoxyalkyl, aryl or arylalkyl, heteroaryl or heteroarylalkyl; R2 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?6, -NR6R7¿, -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.
Abstract:
Compounds having Formula (I) are useful for treating inflammation. Also disclosed are pharmaceutical compositions comprising compouns of Formula (I), and methods of inhibiting/treating inflammatory diseases in a mammal.
Abstract:
The invention relates to compounds having activity to inhibit lipoxygenase enzyme activity, to pharmaceutical compositions comprising these compounds, and to a medical method of treating. More particularly, this invention concerns certain substituted arylalkynyl- and ((heteroaryl)alkynyl)-N-hydroxy-ureas which inhibit leukotriene biosynthesis, to pharmaceutical compositions of these compounds and to a method of inhibiting leukotriene biosynthesis.
Abstract:
Compounds having formula (I) are useful for treating inflammation. Also disclosed are pharmaceutical compositions comprising compounds of formula (I), and methods of inhibiting/treating inflammatory diseases in a mammal.