Steroid receptor modulator compounds and methods

A pharmaceutical composition which modulates progesterone receptor activity comprising an effective amount of a progesterone receptor modulating compound of the formula:

• ##STR86## wherein;
• R.sup.1 is a heteroaryl optionally substituted with a C.sub.1 -C.sub.4 alkyl, F, Cl, Br, NO.sub.2, CO.sub.2 H, CO.sub.2 R.sup.2, CHO, CN, CF.sub.3, CH.sub.2 OH or COCH.sub.3, where R.sup.2 is hydrogen, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, and where said R.sup.1 heteroaryl is attached to compounds of formulas I and X through a carbon or nitrogen atom;
• R.sup.3 is hydrogen, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, hydroxymethyl, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl;
• R.sup.4 through R.sup.5 each independently are hydrogen, F, Cl, Br, I, NO.sub.2, CO.sub.2 H, CO.sub.2 R.sup.2, COR.sup.2, CN, CF.sub.3, CH.sub.2 OH, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, OR.sup.2, SR.sup.2, S(O)R.sup.2, SO.sub.2 R.sup.2, SO.sub.3 H, S(NR.sup.2 R.sup.7)R.sup.2, S(O)(NR.sup.2 R.sup.7)R.sup.2, NR.sup.2 R.sup.7, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, where R.sup.2 has the definition given above, R.sup.7 is hydrogen, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, aryl, heteroaryl, optionally substituted allyl or arylmethyl, OR.sup.8 or NHR.sup.8, where R.sup.8 is hydrogen, a C.sub.1 -C.sub.6 alkyl or perfluoroalkyl, aryl, heteroaryl, optionally substituted allyl or arylmethyl, SO.sub.2 R.sup.2 or S(O)R.sup.2 ;
• R.sup.6 is hydrogen, F, Cl, Br, I, NO.sub.2, COR.sup.2, CN, CF.sub.3, CH.sub.2 OH, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, OR.sup.2, SR.sup.2, S(O)R.sup.2, SO.sub.2 R.sup.2, SO.sup.3 H, S(NR.sup.2 R.sup.7)R.sup.2, S(O)(NR.sup.2 R.sup.7)R.sup.2, NR.sup.2 R.sup.7, aryl heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, where R.sup.2 has the definition given above, R.sup.7 is hydrogen, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, aryl, heteroaryl, optionally substituted allyl or arylmethyl, OR.sup.8 or NHR.sup.8, where R.sup.8 is hydrogen, a C.sub.1 -C.sub.6 alkyl or perfluoroalkyl, aryl, heteroaryl, optionally substituted allyl or arylmethyl, SO.sub.2 R.sup.2 or S(O)R.sup.2 ;
• R.sup.9 and R.sup.10 each independently are hydrogen, a C.sub.1 -C.sub.6 alkyl or perfluoroalkyl, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, or R.sup.9 and R.sup.10 taken together can form a three- to seven-membered ring optionally substituted with hydrogen, F, OR.sup.2, or NR.sup.2 R.sup.7, where R.sup.2 and R.sup.7 have the definitions given above;
• R.sup.11 through R.sup.15 each independently are hydrogen, F, Cl, Br, I, NO.sub.2, CO.sub.2 H, CO.sub.2 R.sup.2, COR.sup.2, CN, CF.sub.3, CH.sub.2 OH, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, OR.sup.2, SR.sup.2, S(O)R.sup.2, SO.sub.2 R.sup.2, SO.sub.3 H, S(NR.sup.2 R.sup.7)R.sup.2, S(O)(NR.sup.2 R.sup.7)R.sup.2, NR.sup.2 R.sup.7, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, where R.sup.2, R.sup.7 and R.sup.8 have the definitions given above;
• X is CH.sub.2, O, S or NR.sup.7, where R.sup.7 has the definition given above;
• R.sup.21 is hydrogen, a C.sub.1 -C.sub.4 alkyl or optionally substituted allyl, arylmethyl, aryl or heteroaryl;
• the dotted lines in the structures depict optional double bonds, except that when there is a C.sub.3 -C.sub.4 double bond in the nitrogen bearing ring of compounds of formula II, then R.sup.11 through R.sup.15 cannot all be hydrogen and R.sup.3, R.sup.9 and R.sup.10 cannot all be methyl, and further except when R.sup.1 of the compounds of formula I is 4-pyridyl, then R.sup.3 through R.sup.6, R.sup.9 and R.sup.10 cannot all be hydrogen, and further yet except that R.sup.3 through R.sup.6 and R.sup.9 through R.sup.15 cannot all be hydrogen in the compounds of formula II;
• and
• a pharmaceutically acceptable carrier.

A method of treating a patient requiring progesterone receptor therapy comprising administering to a patient an effective amount of a progesterone receptor modulating compound having the formula:

• ##STR87## wherein:
• R.sup.1 is a heteroaryl optionally substituted with a C.sub.1 -C.sub.4 alkyl, F, Cl, Br, NO.sub.2, CO.sub.2 H, CO.sub.2 R.sup.2, CHO, CN, CF.sub.3, CH.sub.2 OH or COCH.sub.3, where R.sup.1 is hydrogen, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, and where said R.sup.1 heteroaryl is attached to compounds of formulas I and X through a carbon or nitrogen atom;
• R.sup.3 is hydrogen, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, hydroxymethyl, aryl, heteroaryl or optionally substituted allyl, arylmethyl, akynyl or alkenyl;
• R.sup.4 through R.sup.5 each independently are hydrogen, F, Cl, Br, I, NO.sub.2, CO.sub.2 H, CO.sub.2 R.sup.2, COR.sup.2, CN, CF.sub.3, CH.sub.2 OH, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, OR.sup.2, SR.sup.2, S(O)R.sup.2, SO.sub.2 R.sup.2, SO.sub.3 H, S(NR.sup.2 R.sup.7)R.sup.2, S(O)(NR.sup.2 R.sup.7)R.sup.2, NR.sup.2 R.sup.7, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, where R.sup.2 has the definition given above, R.sup.7 is hydrogen, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, aryl, heteroaryl, optionally substituted allyl or arylmethyl, OR.sup.8 or NHR.sup.8, where R.sup.8 is hydrogen, a C.sub.1 -C.sub.6 alkyl or perfluoroalkyl, aryl, hetoroaryl, optionally substituted allyl or arylmethyl, SO.sub.2 R.sup.2 or S(O)R.sup.2 ;
• R.sup.6 is hydrogen, F, Cl, Br, I, NO.sub.2, COR.sup.2, CN, CF.sub.3, CH.sub.2 OH, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, OR.sup.2, SR.sup.2, S(O)R.sup.2, SO.sub.2 R.sup.2, SO.sub.3 H, S(NR.sup.2 R.sup.7)R.sup.2, S(O)(NR.sup.2 R.sup.7)R.sup.2, NR.sup.2 R.sup.7, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, where R.sup.2 has the definition given above, R.sup.7 is hydrogen, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, aryl, heteroaryl, optionally substituted allyl or arylmethyl, OR.sup.8 or NHR.sup.8, where R.sup.8 is hydrogen, a C.sub.1 -C.sub.6 alkyl or perfluoroalkyl, aryl, heteroaryl, optionally substituted allyl or arylmethyl, SO.sub.2 R.sup.2 or S(O)R.sup.2 ;
• R.sup.9 and R.sup.10 each independently are hydrogen, a C.sub.1 -C.sub.6 alkyl or perfluoroalkyl, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, or R.sup.9 and R.sup.10 taken together can form a three- to seven-membered ring optionally substituted with hydrogen, F, OR.sup.2, or NR.sup.2 R.sup.7, where R.sup.2 and R.sup.7 have the definitions given above;
• R.sup.11 through R.sup.15 each independently are hydrogen, F, Cl, Br, I, NO.sub.2, CO.sub.2 H, CO.sub.2 R.sup.2, COR.sup.2, CN, CF.sub.3, CH.sub.2 OH, a C.sub.1 -C.sub.4 alkyl or perfluoroalkyl, OR.sup.2, SR.sup.2, S(O)R.sup.2, SO.sub.2 R.sup.2, SO.sub.3 H, S(NR.sup.2 R.sup.7)R.sup.2, S(O)(NR.sup.2 R.sup.7)R.sup.2, NR.sup.2 R.sup.7, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl, where R.sup.2, R.sup.7 and R.sup.8 have the definitions given above;
• X is CH.sub.2, O, S or NR.sup.7, where R.sup.7 has the definition given above;
• R.sup.21 is hydrogen, a C.sub.1 -C.sub.4 alkyl or optionally substituted allyl, arylmethyl, aryl or heteroaryl;
• and
• the dotted lines in the structures depict optional double bonds.