Angiogenesis inhibiting thiadiazolyl pyridazine derivatives

A method of inhibiting abnormal angiogenesis in a subject having a disease or disorder associated with abnormal angiogenesis, said disease or disorder selected from the group consisting of solid tumor growth, ocular neovascular diseases, neovascular glaucoma, diabetic retinopathy, retrolental fibroplasia, hemangiomas, angiofibromas, psoriasis, osteoarthritis, and rheumatoid arthritis, comprising administering to said subject an effective amount of a compound of formula (I),

• the N-oxide forms, the pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof, wherein
• R1 is hydrogen, C1-6alkyl, C1-6alkyloxy, C1-6alkylthio, amino, mono- or di(C1-6alkyl)amino, Ar1, Ar1—NH—, C3-6cycloalkyl, hydroxymethyl or benzyloxymethyl;
• R2 and R3 are hydrogen, or taken together may form a bivalent radical of formula —CH═CH—CH═CH—;
• R4, R5 and R6 are each independently selected from hydrogen, halo, C1-6alkyl, C1-6alkyloxy, trifluoromethyl, nitro, amino, cyano, azido, C1-6alkyloxyC1-6alkyl, C1-6alkylthio, C1-6alkyloxycarbonyl or Het1;
• or when R4 and R5 are adjacent to each other they may be taken together to form a radical of formula —CH═CH—CH═CH—;
• A is a bivalent radical of formula
• wherein X is a direct bond, —O—, —S—, C═O, —NR8— or Het2;
• R7 is hydrogen, C1-6alkyl or Ar2methyl;
• R8 is hydrogen, C1-6alkyl or Ar2 methyl;
• Alk1 is C1-6alkanediyl;
• Alk2 is C1-4alkanediyl;
• Ar1 is phenyl;
• phenyl substituted with 1, 2, or 3 substituents each independently selected from halo, C1-6alkyl, C1-6alkyloxy, trihalomethyl, amino or nitro;
• Ar’is phenyl;
• phenyl substituted with 1, 2 or 3 substituents each independently selected from halo, C1-6alkyl, C1-6alkyloxy, trihalomethyl, amino or nitro;
• Het1 is a monocyclic heterocycle selected from oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl or oxazolinyl;
• and each monocyclic heterocycle may optionally be substituted on a carbon atom with C1-4alkyl;
• and
• Het2 is tetrahydrofuran;
• a tetrahydrofuran substituted with C1-6alkyl;
• a dioxane;
• a dioxane substituted with C1-6alkyl;
• a dioxolane;
• or a dioxolane substituted with C1-6alkyl;
• wherein said effective amount comprises from 0.001 mg/kg to 10 mg/kg body weight.