Abstract: The present invention describes pyridazinone compounds of formula I 1

Abstract: The present invention describes pyridazinone compounds of formula I 1

Abstract: The present invention describes pyridazinone compounds of formula I which are cyclooxygenase (COX) inhibitors, and in particular, are selective inhibitors of cyclooxygenase-2 (COX-2). COX-2 is the inducible isoform associated with inflammation, as opposed to the constitutive isoform, cyclooxygenase-1 (COX-1) which is an important “housekeeping” enzyme in many tissues, including the gastrointestinal (GI) tract and the kidneys. The selectivity of these compounds for COX-2 minimizes the unwanted GI and renal side-effects seen with currently marketed non-steroidal anti-inflammatory drugs (NSAIDs).

Abstract: Compounds having Formula I 1

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.

Abstract: Compounds having the formula ##STR1## or a pharmaceutically acceptable salt thereof wherein Y is selected from halogen, alkyl, and haloalkyl; n is 0, 1, 2, or 3; X is absent or is alkylene; A is absent or is selected from optionally substituted alkylene, optionally substituted cycloalkylene, optionally substituted cycloalkylene wherein one or two of the carbon atoms is replaced with one or two heteroatoms independently selected from O, S, and N, optionally substituted alkenylene, and ##STR2## or R.sup.2 and A together define a saturated 5- to 8-membered optionally substituted carbocyclic or heterocyclic ring to which the group Z is attached; Z is selected from (a) hydrogen, (b) COM wherein M is selected from the group consisting of --OR.sup.5, a pharmaceutically acceptable cation, --NR.sup.7 R.sup.8, and a pharmaceutically acceptable, metabolically cleavable group, (c) --OR.sup.3, (d) tetrazolyl, (e) --CH(OR.sup.3)--CH.sub.2 OR.sup.9, (f) --CH(OR.sup.3)--CH.sub.2 --CH.sub.2 OR.sup.9, (g) --CH(OR.sup.

Abstract: Compounds having the formula: ##STR1## 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.sup.1 and R.sup.2 are independently selected from hydrogen, alkyl, halolalkyl, alkoxy, halogen; R.sup.3 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.dbd.N--O--A--COM, (c) CH.sub.2 --O--N.dbd.A--COM wherein A is selected from alkylene and cycloalkylene, and M is selected from (a) a pharmaceutically acceptable metabolically cleavable group, (b) --OR.sup.6, (c) --NR.sup.7 R.sup.8, (d) --NR.sup.6 SO.sub.2 R.sup.

Abstract: Compounds having the formula ##STR1## or a pharmaceutically acceptable salt thereof wherein Y is selected from halogen, alkyl, and haloalkyl; n is 0, 1, 2, or 3; A is selected from (a) optionally substituted alkylene, (b) optionally substituted cycloalkylene, (c) optionally substituted cycloalkylene wherein one or two of the carbon atoms is replaced with one or two heteroatoms independently selected from O, S, and N, (d) optionally substituted alkenylene and (e) ##STR2## X is absent or is alkylene; Z is selected from (a) hydrogen, (b) COM wherein M is selected from --OR.sup.4, --NR.sup.6 R.sup.7, and a pharmaceutically acceptable metabolically cleavable group, (c) --OR.sup.2, (d) tetrazolyl, (e) --CH(OR.sup.2)--CH.sub.2 OR.sup.8, (f) --CH(OR.sup.2)--CH.sub.2 --CH.sub.2 OR.sup.8, (g) --CH(OR.sup.2)--CH(OR.sup.8)--CH.sub.2 OR.sup.9, and (h).dbd.N--OR.sup.2 ; and R.sup.

Abstract: Compounds having the formula: ##STR1## 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.sup.1 and R.sup.2 are independently selected from hydrogen, alkyl, halolalkyl, alkoxy, halogen; R.sup.3 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.dbd.N--O--A--COM, (c) CH.sub.2 --O--N.dbd.A--COM wherein A is selected from alkylene and cycloalkylene, and M is selected from (a) a pharmaceutically acceptable metabolically cleavable group, (b) --OR.sup.6, (c) --NR.sup.7 R.sup.8, (d)--NR.sup.6 SO.sub.2 R.sup.

Abstract: The present invention provides a class of substituted indole and indene iminoxy derivatives of the formula ##STR1## which inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states.

Abstract: Described herein are compounds having the formula ##STR1## or a pharmaceutically acceptable salt thereof wherein L is selected from the group consisting of ##STR2## R.sup.2 is selected from (a) ##STR3## R.sup.3 is selected from optionally substituted phenyl, and optionally substituted pyridyl; Y is selected from halogen, alkyl, haloalkyl, alkoxy, pyridylmethoxy, thiazolylmethoxy, benzothiazolylmethoxy, quinolylmethoxy, and optionally substituted quinolylmethoxy; W is selected from hydrogen, alkyl, hydroxyalkyl, and hydroxy; A is absent or is selected from optionally substituted alkylene optionally substituted cycloalkylene, optionally substituted cycloalkylene wherein one or two of the carbon atoms is replaced with one or two heteroatoms independently selected from O, S, and N, and ##STR4## and X is absent or is alkylene; Z is selected from (a) hydrogen, (b) COM wherein M is selected from (b-1) a pharmaceutically acceptable metabolically cleavable group, (b-2)--OR.sup.10,(b-3)--O(CH.sub.2).sub.w --CH(OR.sup.

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 of the structure ##STR1## where p and q are zero or one, but cannot both be the same, M is a pharmaceutically acceptable cation or a metabolically cleavable group, B is a valence bond or a straight or branched alkylene group, R is alkyl, cycloalkyl or --NR.sup.1 R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl or alkanoyl, and A is optionally substituted carbocyclic aryl, furyl, benzo[b]furyl, thienyl, or benzo[b]thienyl 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.

Abstract: 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.

Abstract: Compounds of the structure ##STR1## wherein Z is selected from optionally substituted thienyl, thiazolyl, oxazolyl and furyl 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.

Abstract: Compounds of the structure ##STR1## where p and q are zero or one, but cannot both be the same, M is a pharmaceutically acceptable cation or a metabolically cleavable group, B is a valence bond or a straight or branched alkylene group, R is alkyl, cycloalkyl or --NR.sup.1 R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl or alkanoyl, and A is optionally substituted carbocyclic aryl, furyl, benzo[b]furyl, thienyl, or benzo[b]thienyl 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.

Abstract: The present invention provides certain substituted oxime ether compounds which inhibit lipoxygenase enzyme activity and are useful in the treatment of allergic and inflammatory disease states. The compounds of this invention have the structure ##STR1## where M is hydrogen, a pharmaceutically acceptable cation, or a pharmaceutically acceptable metabolically cleavable group; p and q are independently zero or one, with the provisos that (i) p and q may not both be the same; (ii) when p is one and q is zero, R is selected from the group consisting of hydrogen, straight or branched alkyl of from one to twelve carbon atoms, and cycloalkyl of from three to eight carbon atoms; and (iii) when p is zero and q is one, R is selected from the group consisting of hydrogen, alkyl of from one to twelve carbon atoms, cycloalkyl of from three to eight carbon atoms, and --NR.sub.1 R.sub.2.L.sub.

Abstract: The present invention relates to compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein Z is selected from optionally substituted phenyl, furyl, thienyl or thiazolyl; which inhibits leukotriene biosynthesis and is useful in the treatment of inflammatory disease states; also disclosed are leukotriene biosynthesis inhibiting compositions and a method for inhibiting 5-lipoxygenase activity and leukotriene biosynthesis.

Abstract: Substituted phenyl, naphthyl, and thienyl N-hydroxy urea compounds form a class of potent inhibitors of 5- and 12-lipoxygenase and are thus useful compounds in the treatment of inflammatory disease states where leukotrienes and other products of lipoxygenase enzyme activity are implicated.

Abstract: 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.