| abstract |
The aminoguanidine and alkoxyguanidine derivative or a solvate, hydrate or pharmaceutically acceptable salt thereof has the formula I wherein: R' is optionally substituted alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl or heteroaryl; Z is -NR10SO2-, -SO2NR10-, -NR10C(RyRz)-, -C(RyRz)NR10-, -OSO2-, -SO2O-, -OC(RyRz)-, -C(RyRz)O-, -NR10CO- or -CONR10-; RY and RZ are independently hydrogen, alkyl, cycloalkyl, aryl, aralkyl, hydroxyalkyl, carboxyalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl or carboxy; R2, R3 and R4 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, heteroaryl, trifluoromethyl, halogen, hydroxyalkyl, cyano, nitro, carboxamido, -CO2RX, -CH2ORX or ORX, or when present on adjacent carbon atoms, R2 and R3 may also be taken together to form one of -CH =CH-CH=CH- or -(CH2)q'- while R4 is defined as above; q' is from 2 to 6 each RX is independently hydrogen or optionally unsaturated alkyl or cycloalkyl; Y is -O-, -NR10-, - S-, -CHR10- or a covalent bond; X is oxygen or NR9; R9 is hydrogen or optionally substituted alkyl, cycloalkyl or aryl; R6 is hydrogen, alkyl, aralkyl, aryl, hydroxyalkyl, aminoalkyl, monoalkylamino alkyl, dialkylamino alkyl or carboxyalkyl or R6 and R12 are taken together to form -(CH2)w; w is 1 to 5; R7 is hydrogen, alkyl, aralkyl, hydroxyalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, carboxyalkyl, hydroxy, alkoxy, aralkoxy, heteroaryloxy, mono or di alkylamino provided than n is other than zero when R7 is hydroxy, alkoxy, aralkoxy, aryloxy, heteroaryloxy or mono or di alkylamino; R8, R11 and R12 are independently hydrogen, alkyl, aralkyl, aryl, hydroxyalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl or carboxyalkyl or R7 and R8 are taken together to form -(CH2)y- while R11 and R12 are defined as above or R7 and R12 are taken together to form -CH2)q while R8 and R11 are defined as above or R8 and R11 are taken together to form -(CH2)r- while R7 and R12 are defined as above; r is 2-8; y is 0 to 2; q is 0 to 8; each R10 is independently hydrogen, alkyl, aralkyl, aryl, hydroxyalkyl, aminoalkyl, monoakylamino alkyl, dialkylamino alkyl or carboxyalkyl; Ra, Rb and Rc are independently hydrogen, alkyl, hydroxy, alkoxy, aryloxy, aralkoxy, alkoxycarbonyloxy, cyano or -CO2Rw; Rw is alkyl, cycloalkyl, phenyl, benzyl or a group of formula II; Rd and Re are independently hydrogen, alkyl, alkenyl or phenyl; Rf is hydrogen, alkyl, alkenyl or phenyl, Rg is hydrogen, alkyl, alkenyl or phenyl; Rh is aralkyl or alkyl; n is 0 to 8 and m is 0 to 4. A pharmaceutical composition thereof is useful for inhibiting proteolysis or for treating pancreatitis, thrombosis, ischemica, stroke, emphysema or inflammation. |