Pro-drugs for CCK antagonists

Claim 1

A compound of the formula ##STR39## or a pharmaceutically acceptable salt thereof wherein: R 1 is a cycloalkyl or polycycloalkyl hydrocarbon of from three to twelve carbon atoms with from zero to four substituents each independently selected from the group consisting of a straight or branched alkyl of from one to about six carbon atoms, halogen, CN, OR*, SR*, CO 2 R*, CF 3 , NR 5 R 6 , and --(CH 2 ) n OR 5 wherein R* is hydrogen, straight or branched alkyl of from one to six carbon atoms, --(CH 2 ) n Ar, --COAr, --(CH 2 ) n OCOAr, or --(CH 2 ) n NR 5 COAr and R* may also independently be R** as defined below, and R** must be present once in formula I, and R** is attached to formula I through a metabolically labile bond, R 5 and R 6 are each independently hydrogen or alkyl of from one to six carbon atoms and n is an integer from zero to six; and R** is --(CH 2 ) n NR 5 R 6 , --(CH 2 ) n --B--D* wherein D* is O--COR*, CO 2 Ar 2 , (CH 2 ) n Ar 2 , OCOAr 2 , NR 5 COAr 2 , COAr 2 , CO 2 CH(R)--CO 2 R*, CO 2 --(CH 2 ) n OCOR* where Ar 2 is independently taken from Ar, where m is as defined below, CONHCH(R)CO 2 R* where R is a side chain of aspartic or glutamic acid, R is hydrogen only when B is not a bond, --CO 2 CH 2 CH 2 N + (R*) 3 X 1- when X 1- is a pharmaceutically acceptable counter anion, A is --(CH 2 ) n CO--, --SO 2 --, --S(═O)--, --NHCO--, --(CH 2 ) n --C(═O)--, ##STR40## --O--(CH 2 ) n CO-- or --HC═CHCO-- wherein n is an integer from zero to six; R 2 is CH 3 ; R 3 and R 4 are each independently selected from hydrogen, R 2 and --(CH 2 ) n , --B--D wherein: n' is an integer of from zero to three; B is a bond, --OCO(CH 2 ) n --, --O(CH 2 ) n --, --NHCO(CH 2 ) n --, --CONH(CH 2 ) n --, --NHCOCH═CH--, --COO(CH 2 ) n --, --CO(CH 2 ) n --, --S--(CH 2 ) n --, --S(═)--(CH 2 ) n --, --SO 2 --(CH 2 ) n --, --NHSO 2 --(CH 2 ) n --, --SO 2 NH--(CH 2 ) n --, ##STR41## wherein R 7 and R 8 are each independently selected from hydrogen and R 2 or together form a ring (CH 2 ) m wherein m is an integer of from 1 to 5 and n is as defined above; D is hydrogen, --COOR*, --CH 2 NR 5 R*, --CHR 2 NR 5 R*, --CH 2 OR*, --CHR 2 OR*, --CH 2 SR*, --CHR 2 SR*, --CONR 5 R 6 , --CONR 5 R*, an acid replacement selected from ##STR42## wherein R*, R 2 , R 5 , and R 6 are as defined above; R 9 is hydrogen or a straight or branched alkyl of from one to six carbon atoms, --(CH 2 ) n CO 2 R*, --(CH 2 ) n NR 5 R*, wherein n, R * , and R 5 are as defined above or taken from R 3 ; R 12 and R 13 are each independently hydrogen or are each independently taken with R 3 and R 4 , respectively, to form a moiety doubly bonded to the carbon atom; and Ar is a mono- or polycyclic unsubstituted or substituted carbo- aromatic or carbo- hydroaromatic moiety.