Tricyclic derivatives, compositions and methods of use
AssigneeSchering Corporation
InventorsPauline C. Ting, Richard J. Friary, Wing C. Tom, Joe F. Lee, Vera A. Seidl
Life of this patent
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Abstract
Disclosed are compounds of Formula I: ##STR1## or a pharmaceutically acceptable salt or solvate thereof, wherein: R.sup.4 is alkenyl, alkoxy, or --OH. Also disclosed are pharmaceutical compositions containing compounds of Formula I, methods for inhibiting tumor necrosis factor-.alpha., and methods for treating septic shock, inflammation, or allergic disease.
Claims21
A compound of the Formula I:
- ##STR34## or a pharmaceutically acceptable salt or solvate thereof, wherein:
- each of T and U represents CH;
- one of V and W represents oxygen and the other represents --CH.sub.2 --;
- or each of V and W represent --CH.sub.2 --;
- R.sup.1 and R.sup.2 are each independently selected from the group consisting of H and halogen;
- R.sup.4 is alkenyl or alkoxy;
- represents an optional double bond;
- when is a double bond, Z represents --CH.dbd., or --CH.sub.2 C(R.sup.5).dbd., wherein R.sup.5 is H or lower alkyl;
- and R.sup.7 and R.sup.8 together represent OR.sup.9 ;
- when represents a single bond, Z represents --CH.sub.2 --, --CH.dbd.CH--, or --CH.sub.2 C(R.sup.5)(R.sup.6)--, wherein R.sup.5 and R.sup.6 are independently H or lower alkyl;
- and R.sup.7 and R.sup.8 are independently H, alkyl, alkenyl, alkynyl, aryl, alkaryl, aralkyl, cycloalkyl, --OR.sup.9 ;
- --C(O)OR.sup.10 ;
- --CH.sub.2 C(O)OR.sup.9 ;
- --C(O)R.sup.10 ;
- --SO.sub.2 R.sup.10 ;
- --(CH.sub.2).sub.n --N(CH.sub.3).sub.2, where n is 2 to 4;
- --(CH.sub.2).sub.m O(CH.sub.2).sub.j OH, where m and j are independently 2 or 3;
- ##STR35## R.sup.9 is H or lower alkyl;
- and R.sup.10 is alkyl or aryl.
A pharmaceutical composition comprising an effective amount of a compound of the following structure IA in combination with a pharmaceutically acceptable carrier:
- ##STR39##
A method of inhibiting tumor necrosis factor-.alpha. comprising administering to a mammal in need of such inhibition an effective anti-tumor necrosis factor amount of a compound having the following formula K:
- ##STR40## or a pharmaceutically acceptable salt or solvate thereof, wherein:
- each of T and U represents CH;
- one of V and W represents oxygen and the other represents --CH.sub.2 --;
- or each of V and W represents --CH.sub.2 --;
- R.sup.1 and R.sup.2 are each independently selected from the group consisting of H and halogen;
- R.sup.4 is H or alkyl;
- represents an optional double bond;
- when
- is a double bond, Z represents --CH.dbd., or --CH.sub.2 C(R.sup.5).dbd., wherein R.sup.5 is H or lower alkyl;
- and R.sup.7 and R.sup.8 together represent OR.sup.9 ;
- represents a single bond, Z represents --CH.sub.2 --, --CH.dbd.CH--, or --CH.sub.2 C(R.sup.5)(R.sup.6)--, wherein R.sup.5 and R.sup.6 are independently H or lower alkyl;
- and R.sup.7 and R.sup.8 are independently H, alkyl, alkenyl, alkynyl, aryl, alkaryl, aralkyl, cycloalkyl --OR.sup.9 ;
- --C(O)OR.sup.10 ;
- --CH.sub.2 C(O)OR.sup.9 ;
- --C(O)R.sup.10 ;
- --SO.sub.2 R.sup.10 ;
- --(CH.sub.2).sub.n --N(CH.sub.3).sub.2, where n is 2 to 4;
- --(CH.sub.2 .sub.)m O(CH.sub.2).sub.j OH, where m and j are
- independently 2 or 3;
- ##STR41## R.sup.9 is H or lower alkyl;
- and R.sup.10 is alkyl or aryl.
Dependencies are inferred from the claim text.