Substituted hydrindanes for the treatment of angiogenesis-dependent diseases

A method for controlling neovascularization in warm blooded animals, which comprises administering to the animal a pharmaceutically effective amount of a substituted hydrindane having the following structure ##STR7## where X is OH, OR.sub.1, OR.sub.2, OS(O).sub.2 R.sub.3, ON.dbd.CHR.sub.1, ON.dbd.CR.sub.1 R.sub.1, CN, R.sub.1, R.sub.2, CH(OH)R.sub.2, CH(OR.sub.1)R.sub.2, CH(OR.sub.2)R.sub.2, C(OH)R.sub.1 R.sub.1, C(OR.sub.1)R.sub.1 R.sub.1, C(OR.sub.2)R.sub.1 R.sub.1, C(OH)R.sub.1 R.sub.2, C(OR.sub.1)R.sub.1 R.sub.2, C(OR.sub.2)R.sub.1 R.sub.2, C(OH)R.sub.2 R.sub.2, C(OR.sub.1)R.sub.2 R.sub.2, C(OR.sub.2)R.sub.2 R.sub.2, S(.dbd.O).sub.n H, S(.dbd.O).sub.n R.sub.1, SR.sub.2, P(.dbd.O)R.sub.1 R.sub.1, P(.dbd.O)(OH).sub.2, P(.dbd.O)(OH)(OR.sub.1), P(.dbd.O)(OR.sub.1)(OR.sub.1), P(.dbd.O)(OH)(NH.sub.2), P(.dbd.O)(OR.sub.1)(NH.sub.2), P(.dbd.O)(OH)(NHR.sub.1), P(.dbd.O)(OH)(NR.sub.1 R.sub.1), P(.dbd.O)(OR.sub.1)(NHR.sub.1) P(.dbd.O)(OR.sub.1)(NR.sub.1 R.sub.1), NH.sub.2, NHR.sub.1, NHR.sub.2, NR.sub.1 R.sub.1, NR.sub.1 R.sub.2, NHOH, N(OH)R.sub.1, N(OH)R.sub.2, NH(OR.sub.1), NH(OR.sub.2), N(OR.sub.1)R.sub.2, N(OR.sub.2)R.sub.1, N(OR.sub.2)R.sub.2, N(OR.sub.1)R.sub.1, .sup..sym. S(R.sub.1)(R.sub.1)Q.sup..crclbar., .sup..sym. N(R.sub.1)(R.sub.1)(R.sub.1)Q.sup..crclbar. wherein Q.sup..crclbar. is a halide, sulfonate, or carboxylate anion;

• C(.dbd.O)R.sub.1, C(.dbd.O)R.sub.2, C(.dbd.O)NH.sub.2, C(.dbd.O)NHR.sub.1, C(.dbd.O)NR.sub.1 R.sub.1, C(.dbd.O)N(OH)R.sub.1, C(.dbd.O)N(OR.sub.1)R.sub.1, C(.dbd.O)N(OR.sub.2)R.sub.1 ;
• or ##STR8## n=0, 1 or 2;
• R.sub.1 is aryl, haloaryl, C.sub.1 -C.sub.10 alkyl, branched alkyl, cycloalkyl, aralkyl, carboxyalkyl or haloalkyl, optionally unsaturated and/or substituted with up to 6 OH, 6 OR.sub.3, or 6 OR.sub.2 ;
• or imidazolyl, triazolyl, thiadiazolyl, oxadiazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, or pyridyl, optionally substituted with up to three halogen or C.sub.1 -C.sub.6 alkyl groups;
• R.sub.2 is C(.dbd.O)H, C(.dbd.O)R.sub.1, C(.dbd.O)OR.sub.1, C(.dbd.O)OH, C(.dbd.O)NH.sub.2, C(.dbd.O)NHR.sub.1, C(.dbd.O)NR.sub.1 R.sub.1 ;
• R.sub.3 is aryl, haloaryl, C.sub.1 -C.sub.10 alkyl, branched alkyl, cycloalkyl, aralkyl, carboxyalkyl or haloalkyl optionally unsaturated and/or substituted with up to 6 OH;
• R.sub.4 is H, (.dbd.O), OR.sub.2, OR.sub.1, OH, .dbd.NOH, .dbd.NOR.sub.1, .dbd.NOR.sub.2 ;
• R.sub.5 and R.sub.6 are independently H, CH.sub.3 or CH.sub.2 CH.sub.3 ;
• Y is H, OH, OR.sub.1, OR.sub.2 or (.dbd.O), with the proviso that if Y is OH, then X is R.sub.1, R.sub.2, CH(OH)R.sub.2, CH(OR.sub.1)R.sub.2, CH(OR.sub.2)R.sub.2, C(OH)R.sub.1 R.sub.2, C(OR.sub.1)R.sub.1 R.sub.2, C(OR.sub.2)R.sub.1 R.sub.2, C(OH)R.sub.2 R.sub.2, C(OR.sub.1)R.sub.2 R.sub.2, C(OR.sub.2)R.sub.2 R.sub.2, and if Y is (.dbd.O) then X is R.sub.1, R.sub.2, CH(OH)R.sub.2, CH(OR.sub.1)R.sub.2, CH(OR.sub.2)R.sub.2, C(OH)R.sub.1 R.sub.2, C(OR.sub.1)R.sub.1 R.sub.2, C(OR.sub.2)R.sub.1 R.sub.2, C(OH)R.sub.2 R.sub.2, C(OR.sub.1)R.sub.2 R.sub.2, C(OR.sub.2)R.sub.2 R.sub.2, NH.sub.2, NHR.sub.1, NR.sub.1 R.sub.1, NHOH, N(OH)R.sub.1, NH(OR.sub.1), NH(OR.sub.2).sub.2, N(OR.sub.1 R)R.sub.1, or N(OR.sub.2)R.sub.1 ;
• R.sub.7 and R.sub.8 are independently H or C.sub.1 to C.sub.6 alkyl, branched alkyl, hydroxyalkyl, optionally unsaturated;
• or R.sub.7 and R.sub.8 together form a double bond;
• R.sub.1 R.sub.1 attached to the same C, S, P or N atom taken together can form a ring of from 3 through 7 members;
• and
• for those substituents containing more than one R.sub.1, R.sub.2, or R.sub.3 each R.sub.1, R.sub.2, or R.sub.3 may be the same or different;
• or a pharmaceutically acceptable salt or ester thereof.