| 摘要 |
A 3-(1,2,4-thiadiazol-5-yl)-pyridazine derivative or its N-oxide forms, pharmaceutically acceptable acid addition salts and stereochemically isomeric forms thereof has the formula (I) wherein: R1 is hydrogen, alkyl, alkyloxy, alkylthio, amino, mono- or di-alkyl amino, Ar1, Ar1-NH-, cycloalkyl, 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 hydrogen, halo, alkyl, alkyloxy, trifluoromethyl, nitro, amino, cyano, azido, alkyloxyalkyl, alkylthio, alkyloxycarbonyl 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 -N(R7)-, -N(R7)-Alk1-X-, -N(R7)-Alk1-X-Alk2-, -O-Alk1-X-, -Alk1-X-Alk2-O- or -S-Alk1-; X is a direct bond, -O-, -S-, -C=O, -NR8- or Het2; R7 and R8 are independently hydrogen, alkyl or Ar2-methyl; Alk1 and Alk2 are independently alkanediyl; Ar1 and Ar2 are independently optionally substituted phenyl; Het1 is optionally substituted oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl or oxazolinyl; and Het2 is optionally alkyl substituted tetrahydrofuran, dioxane or dioxolane. A pharmaceutical composition thereof is useful for treating angiogenesis dependent disorders. |
