| abstract |
SUMMARY OF THE INVENTION The present invention relates to a somatostatin indopamine chimeric analog of formula (I) and their therapeutic use, which have both the in vivo effects of somatostatin and dopamine, including many that possess greater biological activity than natural somatostatin and dopamine analogs. A compound of Formula I wherein X is hydrogen, chloro, bromo, iodo, fluoro, -CN, or C 1-5 alkyl; R 1 is hydrogen, C 1-4 alkyl, allyl, alkenyl or -CN; R2 and R3 are independently hydrogen or absent, provided that when R2 and R3 are absent, there is a double bond between the two carbon atoms on which R2 and R3 are located; R 4 is hydrogen or -CH 3; Y is -O-, -C (O) -, -S-, -S (O) -, -S (O) 2 -, -SC (O) -, -OC (O) -, -S - (CH 2) SC (O) -, -N (R 5) -C (O) -, or -N (R 6) -; R 5, R 6, R 7 and R 8 are each independently hydrogen or C 1-5 alkyl; R6 is hydrogen or C1-C5 alkyl; m is 0 or 1; n is 0 to 10; L is - (CH 2) p C (O) - when Y is -S-, -S (O) -, -S (O) 2 -, -O- or -N (R 6) -. group; L is -C (O) - (CR 7 R 8) q -C (O) - when Y is -N (R 6) -, -O-, or -S-; L is - (Doc) t - when Y is -C (O) -, SC (O) -, -OC (O) - or -S- (CH 2) SC (O) -, -N (R 5) -C (O-) -; p is 1-10; q is 2-4; s is 1-10, t is 1-10 and Z is a somatostatin analog or monohydrogen, -OH, C 1-6 alkoxy, arylalkoxy, NH 2, or NR 9 R 10, wherein each R 9 and R 10 is independently hydrogen or C 1 -C 5 alkyl; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions containing the compounds. SHE |