The invention provides compounds of formula (I), their pharmaceutically acceptable salts and prodrugs thereof for use in preventing, inhibiting or treating a disease caused by a mutation in the gene coding for hydroxymethylbilane synthase, in particular for preventing, inhibiting or treating acute intermittent porphyria: (I) wherein: A is selected from N and CR.sup.10 (wherein R.sup.10 is H, —NO.sub.2, C.sub.1-6 haloalkyl or —C(O)R.sup.17 in which R.sup.17 is H or C.sub.1-6 alkyl); Z is selected from N and CR.sup.9 (wherein R.sup.9 is H, halogen (e.g. F, Cl, Br or I) or —OR.sup.16 in which R.sup.16 is H, C.sub.1-6 haloalkyl, or optionally substituted C.sub.1-6 alkyl); L is selected from —CH.sub.2—, —C(O)—, —CH(OH)—, —C(O)—NR′—, and —NR′—C(O)— (wherein R′ is H or C.sub.1-3 alkyl, e.g. —CH.sub.3); R.sup.1 is H; R.sup.2 is selected from H, halogen (e.g. F, Cl, Br or I), —NR.sup.11R.sup.12 (wherein R.sup.11 and R.sup.12 are independently selected from H and C.sub.1-6 alkyl or, together with the nitrogen atom to which they are attached, form a 5- or 6-membered saturated ring), and —OR13 (wherein R.sup.13 is H or C.sub.1-6 alkyl); R.sup.3 is selected from H, —CH.sup.2OH and —C(O)R.sup.14 (wherein R.sup.14 is H or C.sub.1-6 alkyl); R.sup.4 is selected from H, halogen (e.g. F, Cl, Br or I) and —OR.sup.15 (where R.sup.15 is H or C.sub.1-6 alkyl); R.sup.5 is selected from H and C.sub.1-6 alkyl; R.sup.6 is selected from H, —NO.sub.2 and halogen (e.g. F, Cl, Br or I); R.sup.7 is H; and R.sup.8 is selected from H, C.sub.1-6 alkyl, and halogen (e.g. F, Cl, Br or I); or wherein: R.sup.7 and R.sup.8 together with the intervening ring carbon atoms form an unsaturated ring, preferably an aryl ring.

##STR00001##

Provided are compositions and methods for treating osteoarthritis including intra-articular administration of a compound of Formula (I) ##STR00001##
including amorphous and polymorph forms thereof.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

Disclosed are compounds of Formulas (I), (II), (III), (IV), and (V): ##STR00001##
and/or a salt thereof, wherein R.sub.1 is —OH or —OP(O)(OH).sub.2, and X.sub.1, X.sub.2, X.sub.3, R.sub.2, R.sub.2a, R.sub.a, R.sub.b, and R.sub.c are defined herein. Also disclosed are methods of using such compounds as selective agonists for G protein-coupled receptor S1P.sub.1, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating, preventing, or slowing the progression of diseases or disorders in a variety of therapeutic areas, such as autoimmune diseases and vascular disease.

The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.

The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.

Pharmaceutical formulations and methods for the topical or transdermal delivery of 1isobutyl-1H-imidazo[4,5-c]-quinolin-4-amine or 1-(2-methylpropyl)-1H-imidazo[4,5 c]quinolin-4-amine, i.e., imiquimod, to treat genital/perianal warts with shorter durations of therapy than currently prescribed for the commercially available for Aldara® 5% imiquimod cream, as now approved by the U.S. Food & Drug Administration (“FDA”), are disclosed and described. More specifically, lower dosage strength imiquimod formulations to deliver an efficacious dose of imiquimod for treating genital/perianal warts with an acceptable safety profile and dosing regimens that are shorter and more convenient for patient use than the dosing regimen currently approved by the U.S. Food & Drug Administration (“FDA”) for Aldara® 5% imiquimod cream to treat genital/perianal warts are also disclosed and described.

Pharmaceutical formulations and methods for the topical or transdermal delivery of 1isobutyl-1H-imidazo[4,5-c]-quinolin-4-amine or 1-(2-methylpropyl)-1H-imidazo[4,5 c]quinolin-4-amine, i.e., imiquimod, to treat genital/perianal warts with shorter durations of therapy than currently prescribed for the commercially available for Aldara® 5% imiquimod cream, as now approved by the U.S. Food & Drug Administration (“FDA”), are disclosed and described. More specifically, lower dosage strength imiquimod formulations to deliver an efficacious dose of imiquimod for treating genital/perianal warts with an acceptable safety profile and dosing regimens that are shorter and more convenient for patient use than the dosing regimen currently approved by the U.S. Food & Drug Administration (“FDA”) for Aldara® 5% imiquimod cream to treat genital/perianal warts are also disclosed and described.

Provided herein are compounds and pharmaceutical compositions thereof for treating a birthmark in a subject in need thereof, wherein the compound is according to any one of formula (I), (II), (III), (IV), and (V). wherein, X.sup.1, X.sup.2, X.sup.3, R.sup.1, R.sup.2, R.sup.2a, R.sup.13, R.sup.13a, R.sup.23, R.sup.23a, R.sup.23b, R.sup.33, R.sup.33a, R.sup.33b, R.sup.43, R.sup.43a, R.sup.51, R.sup.53, R.sup.53a, R.sup.53b, bond “a”, and subscript n are described herein.

Provided herein are compounds and pharmaceutical compositions thereof for treating a birthmark in a subject in need thereof, wherein the compound is according to any one of formula (I), (II), (III), (IV), and (V). wherein, X.sup.1, X.sup.2, X.sup.3, R.sup.1, R.sup.2, R.sup.2a, R.sup.13, R.sup.13a, R.sup.23, R.sup.23a, R.sup.23b, R.sup.33, R.sup.33a, R.sup.33b, R.sup.43, R.sup.43a, R.sup.51, R.sup.53, R.sup.53a, R.sup.53b, bond “a”, and subscript n are described herein.