Steroid receptor modulator compounds and methods

A pharmaceutical composition which modulates progesterone receptor or having glucocorticoid receptor antagonist activity comprising an effective amount of a progesterone receptor modulating or gtucocorticoid receptor antagonist compound of the formula:

• ##STR86## wherein:
• 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;
• 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.5 through R.sup.6 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, hcteroaryl, 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 or optionally substituted allyl, arylmethyl, SO.sub.2 R.sup.2 or S(O)R.sup.2 ;
• R.sup.9 and R.sup.10 each independently are hydogen, 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.14 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.16 is hydrogen, OH, OR.sup.17, SR.sup.17, NR.sup.2 R.sup.7, optionally substituted allyl, arylmethyl, alkynyl, alkenyl, aryl, heteroaryl or C.sub.1 -C.sub.10 alkyl, where R.sup.17 is a C.sub.1 -C.sub.10 alkyl or perfluoroalkyl, or is an optionally substituted allyl, arylmethyl, aryl or heteroaxyl, and where R.sup.2 and R.sup.7 have the definitions given above;
• R.sup.18 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.18 and R.sup.19 taken together can form a three- to seven-membered ring optionally substituted with hydrogen, F, OR.sup.2, or NR.sup.7 R.sup.8, where R.sup.2, R.sup.7 and R.sup.8 have the definitions given above;
• R.sup.20 is a C.sub.1 -C.sub.6 alkyl or an optionally substituted allyl, arylmethyl, alkenyl, aryl or heteroaryl;
• R.sup.21 is hydrogen, a C.sub.1 -C.sub.4 alkyl or optionally substituted allyl, arylmethyl, aryl or heteroaryl;
• R.sup.30 and R.sup.31 each independently are hydrogen, a C.sub.1 -C.sub.6 alkyl or an optionally substituted allyl, arylmethyl, aryl or heteroaryl, or R.sup.30 and R.sup.31 taken together can form a three- to seven-membered ring optionally substituted with hydrogen, F, Cl, OR.sup.2 or NR.sup.2 R.sup.7, where R.sup.2 and R.sup.7 have the definitions given above;
• the wavy line in the compounds of formula XVI represent an olefin bond in either the cis or trans configuration;
• the dotted lines in the structures depict optional double bonds;
• and
• a pharmaceutically acceptable carrier.

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

• ##STR87## wherein:
• R.sup.2 is hydrogen, a C.sub.1 -C.sub.4 or perfluoroalkyl, aryl, heteroaryl or optionally substituted allyl, arylmethyl, alkynyl or alkenyl;
• 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.5 through R.sup.6 each independently are hydogen, F, Cl, Br, I, NO.sub.2, CO.sub.2 II, CO.sub.2 R.sup.2, COR.sup.2, CN, CF.sub.3, CH.sub.2 OH, a C.sub.1 -C.sub.4 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 or optionally substituted allyl, arymethyl, 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, alklynyl 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.14 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.16 is hydrogen, OH, OR.sup.17, NR.sup.17, NR.sup.2 R.sup.7, optionally substituted allyl, arylmethyl, alkynyl, alkenyl, aryl, hcteroaryl or C.sub.1 -C.sub.10 alkyl, where R.sup.17 is a C.sub.1 -C.sub.10 alkyl or perfluoroalkyl, or is an optionally substituted allyl, arylmethyl, aryl or heteroaryl, and where R.sup.2 and R.sup.7 have the definitions given above;
• R.sup.18 and R.sup.19 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.18 and R.sup.19 taken together can form a three- to seven-membered ring optionally substituted with hydrogen, F, OR.sup.2, or NR.sup.7 R.sup.8, where R.sup.2, R.sup.7 and R.sup.8 have the definitions given above;
• R.sup.20 is a C.sub.1 -C.sub.6 alkyl or an optionally substituted allyl, arylmethyl, alkenyl, aryl or heteroaryl;
• R.sup.21 is hydrogen, a C.sub.1 -C.sub.4 alkyl or optionally substituted allyl, arylmethyl, aryl or heteroaryl;
• R.sup.30 and R.sup.31 each independently are hydrogen, a C.sub.1 -C.sub.6 alkyl or an optionally substituted allyl arylmethyl, aryl or heteroaryl, or R.sup.30 and R.sup.31 taken together can form a three- to seven-membered ring optionally substituted with hydrogen, F, Cl, OR.sup.2 or NR.sub.2 R.sup.7, where R.sup.2 and R.sup.7 have the definitions given above;
• the wavy line in the compounds of formula XVI represent an olefin bond in either the cis or trans configuration;
• and
• the dotted lines in the structures depict optional double.