Pro-drugs for the improved delivery of certain selected anti-inflammatory steroids

Claim 1

A pro-drug compound of the formula: ##STR36## wherein Z represents a member selected from the group consisting of ═O, β--OH and β--O--R 1 , wherein R 1 represents ##STR37## wherein R 4 represents a member selected from the group consisting of H and straight or branched C 1 -C 4 alkyl, and wherein R 2 and R 3 which may be the same or different, represent a member selected from the group consisting of H, straight or branched C 1 -C 8 alkyl, substituted C 1 -C 8 alkyl, wherein at least one of the hydrogen atoms therein is substituted by a member selected from the group consisting of --N(R 4 ) 2 , --CON(R 4 ) 2 , a halogen atom, --COOR 4 , --COOCH 2 N(R 4 ) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined as above, and wherein R 2 and R 3 further represent a member selected from the group consisting of ##STR38## wherein W represents a member selected from the group consisting of --N(R 4 ) 2 , --CON(R 4 ) 2 , a halogen atom, --COOR 4 , --COOCH 2 N(R 4 ) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined as above, with the proviso that R 2 and R 3 cannot simultaneously be H or wherein R 2 and R 3 taken together further represent a member selected from the group consisting of cyclic alkyl [-(CH 2 ) n -] and cyclic heteroalkyl, wherein one of the carbon atoms is substituted by a member selected from the group consisting of <N--R 4 , <N--COR 4 and --CO, wherein n is an integer of 5 to 7 and wherein R 4 is defined as above; wherein Q represents ##STR39## wherein R 4 is defined as above, and R 5 represents H, COOR 4 and --CON(R 4 ) 2 , wherein R 4 is defined as above, provided that the C 4 -C 5 double bond in formula (I) is subject to migration to the C 5 -C 6 position; and wherein with respect to ring (A) in formula (I), the bond between C 1 and C 2 can be a single or double bond: ##STR40## wherein Z represents a member selected from the group consisting of ═O and β--OH; wherein R 6 represents a member selected from the group consisting of H and ##STR41## with the proviso that one of said R 6 is H, wherein R 7 represents a member selected from the group consisting of a C 1 -C 12 straight, branched or cycloalkyl, a C 1 -C 12 straight, branched or cycloalkenyl, a substituted C 1 -C 12 straight, branched or cycloalkyl or alkenyl, ##STR42## --(CH 2 ) n --CON(R 2 ) 2 , wherein n is an integer of 1 to 6, a 2, 3 or 4 pyridyl, wherein at least one of the hydrogen atoms therein can be substituted by a member selected from the group consisting of --N(R 4 ) 2 , --CON(R 4 ) 2 , --SOR 4 , a halogen atom, --COOR 4 , --COOCH 2 N(R 4 ) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined above, ##STR43## wherein W is defined above; wherein Q represents ##STR44## wherein R 4 is defined as above and R 5 represents a member selected from the group consisting of H, COOR 4 and --CON(R 4 ) 2 , wherein R 4 is defined as above; wherein the bond between C 1 and C 2 in ring "A" of formula (II) can be a single or a double bond; and wherein, with respect to ring "A" in formula (II), the double bond between C 4 and C 5 is subject to migration to the C 5 -C 6 position.

Claim 25

A method for alleviating inflammation in or on a warm-blooded aniamal exhibiting an inflammatory response which comprises administering thereto, an anti-inflammatory effective amount of a pro-drug compound of the formula: ##STR54## wherein Z respresents a member selected from the group consisting of ═O, β--OH and β--O--R 1 , wherein R 1 represents ##STR55## wherein R 4 represents a member selected from the group consisting of H and straight or branched C 1 -C 4 alkyl, and wherein R 2 and R 3 which may be the same or different, represent a member selected from the group consisting of H, straight or branched C 1 -C 8 alkyl, substituted C 1 -C 8 alkyl, wherein at least one of the hydrogen atoms therein is substituted by a member selected from the group consisting of --N(R 4 ) 2 , --CON(R.sub. 4) 2 , a halogen atom, --COOR 4 , --COOCH 2 N(R 4 ) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined as above, and wherein R 2 and R 3 further represent a member selected from the group consisting of ##STR56## wherein W represents a member selected from the group consisting of --N(R.sub. 4 .sub. 2, --CON(R.sub. 4) 2 , a halogen atom, --COOR 4 , --COOCH 2 N(R.sub. 4) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined as above, with the proviso that R 2 and R 3 cannot simultaneously be H or wherein R 2 and R 3 taken together further represent a member selected from the group consisting of cyclic alkyl [--(CH 2 ) n --] and cyclic heteroalkyl, wherein one of the carbon atoms is substituted by a member selected from the group consisting of N--R 4 , N--COR 4 and --CO, wherein n is an integer of 5 to 7 and wherein R 4 is defined as above; wherein O represents ##STR57## wherein R 4 is defined as above, and R 5 represents H, COOR 4 and --CON(R.sub. 4) 2 , wherein R 4 is defined as above, provided the C 4 -C 5 double bond in formula (I) is subject to migration to the C 5 -C 6 position; and wherein with respect to ring (A) formula (I), the bond between C 1 and C 2 can be a single or double bond. ##STR58## wherein Z represents a member selected from the group consisting of ═O and β--OH; wherein R 6 represents a member selected from the group consisting of H and ##STR59## with the proviso that one of said R 6 is H, wherein R 7 represents a member selected from the group consisting of a C 1 -C 12 straight, branched or cycloalkyl, a C 1 -C 12 straight, branched or cycloalkenyl, a substituted C 1 -C 12 straight, branched or cycloalkyl or alkenyl, ##STR60## --(CH 2 ) n --CON(R 2 ) 2 , wherein n is an integer of 1 to 6, a 2, 3 or 4 pyridyl, wherein at least one of the hydrogen atoms therein can be substituted by a member selected from the group consisting of --N(R 4 ) 2 , --CON(R 4 ) 2 , --SOR 4 , a halogen atom, --COOR 4 , --COOCH 2 N(R 4 ) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined above, ##STR61## wherein W is defined above; wherein Q represents ##STR62## wherein R 4 is defined as above and R 5 represents a member selected from the group consisting of H, COOR 4 and --CON(R 4 ) 2 , wherein R 4 is defined as above; wherein the bond between C 1 and C 2 in ring "A" of formula (II) can be a single or a double bond; and wherein, with respect to ring "A" in formula (II), the double bond between C 4 and C 5 is subject to migration to the C 5 -C 6 position.

Claim 26

A method for alleviating inflammation in or on a warm-blooded aniamal exhibiting an inflammatory response which comprises administering thereto, an anti-inflammatory effective amount of a pro-drug compound of the formula: ##STR54## wherein Z respresents a member selected from the group consisting of ═O, β--OH and β--O--R 1 , wherein R 1 represents ##STR55## wherein R 4 represents a member selected from the group consisting of H and straight or branched C 1 -C 4 alkyl, and wherein R 2 and R 3 which may be the same or different, represent a member selected from the group consisting of H, straight or branched C 1 -C 8 alkyl, substituted C 1 -C 8 alkyl, wherein at least one of the hydrogen atoms therein is substituted by a member selected from the group consisting of --N(R 4 ) 2 , --CON(R.sub. 4) 2 , a halogen atom, --COOR 4 , --COOCH 2 N(R 4 ) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined as above, and wherein R 2 and R 3 further represent a member selected from the group consisting of ##STR56## wherein W represents a member selected from the group consisting of --N(R.sub. 4 .sub. 2, --CON(R.sub. 4) 2 , a halogen atom, --COOR 4 , --COOCH 2 N(R.sub. 4) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined as above, with the proviso that R 2 and R 3 cannot simultaneously be H or wherein R 2 and R 3 taken together further represent a member selected from the group consisting of cyclic alkyl [--(CH 2 ) n --] and cyclic heteroalkyl, wherein one of the carbon atoms is substituted by a member selected from the group consisting of N--R 4 , N--COR 4 and --CO, wherein n is an integer of 5 to 7 and wherein R 4 is defined as above; wherein O represents ##STR57## wherein R 4 is defined as above, and R 5 represents H, COOR 4 and --CON(R.sub. 4) 2 , wherein R 4 is defined as above, provided the C 4 -C 5 double bond in formula (I) is subject to migration to the C 5 -C 6 position; and wherein with respect to ring (A) formula (I), the bond between C 1 and C 2 can be a single or double bond. ##STR58## wherein Z represents a member selected from the group consisting of ═O and β--OH; wherein R 6 represents a member selected from the group consisting of H and ##STR59## with the proviso that one of said R 6 is H, wherein R 7 represents a member selected from the group consisting of a C 1 -C 12 straight, branched or cycloalkyl, a C 1 -C 12 straight, branched or cycloalkenyl, a substituted C 1 -C 12 straight, branched or cycloalkyl or alkenyl, ##STR60## --(CH 2 ) n --CON(R 2 ) 2 , wherein n is an integer of 1 to 6, a 2, 3 or 4 pyridyl, wherein at least one of the hydrogen atoms therein can be substituted by a member selected from the group consisting of --N(R 4 ) 2 , --CON(R 4 ) 2 , --SOR 4 , a halogen atom, --COOR 4 , --COOCH 2 N(R 4 ) 2 and --COOCH 2 --S--R 4 , wherein R 4 is defined above, ##STR61## wherein W is defined above; wherein Q represents ##STR62## wherein R 4 is defined as above and R 5 represents a member selected from the group consisting of H, COOR 4 and --CON(R 4 ) 2 , wherein R 4 is defined as above; wherein the bond between C 1 and C 2 in ring "A" of formula (II) can be a single or a double bond; and wherein, with respect to ring "A" in formula (II), the double bond between C 4 and C 5 is subject to migration to the C 5 -C 6 position.