Diphenyl substituted cyclohexane derivatives, useful as modulators of the estrogen receptors beta

A compound of formula (I):

• as a single isomer, a mixture of isomers or a racemic mixture of isomers;
• or a solvate or polymorph thereof, or a metabolite or prodrug thereof, or a pharmaceutically acceptable salt thereof,
• wherein:
• R is selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 alkenyl, C1-6 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkenyl, substituted or unsubstituted C3-8 aryl, substituted or unsubstituted C3-8 heteroaryl, substituted or unsubstituted C3-8 heteroalicyclyl, C1-6 haloalkyl, sulfonyl, —C(═Z)R4, —C(═Z)OR4, —C(═Z)NR4aR4b, —S(O)NR4aR4b, —S(O)2NR4aR4b, —P(═O)(OR4), and —CH2O(C═O)R4, wherein R4, R4a and R4b are selected from the groups defined below;
• R1a, R1b, R1c and R1d are separately selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkyl(C3-6 cycloalkyl), halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —C(Z)R4, —C(═Z)OR4, —C(═Z)NR4aR4b, —C(R4)═NR4a, —NR4aR4b, —N═CR4aR4b, —N(R4)C(═Z)R4, —N(R4)—C(═Z)NR4aR4b, —S(O)NR4aR4b, —S(O)2NR4aR4b, —N(R4)—S(═O)R4, —N(R4)S(═O)2R4, —OR4, SR4, and —OC(═Z)R4, wherein each R4, R4a, and R4b is separately selected from the groups defined below;
• or
• two of R1a, R1b, R1c, R1d and R3 (as defined below) on adjacent carbons, taken together with the two intervening carbons to which they are attached, form a C3-6 cycloalkenyl, aryl, heteroaryl or C2-6 heterocycloalkyl group;
• R2a, R2b, R2c and R2d are separately selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C1-6 alkyl(C3-6 cycloalkyl), halogen, C1-6 haloalkyl, C1-6 haloalkoxy, —CN, —C(═Z)OR4, —C(═Z)NR4aR4b, —C(R4)═NR4a, NR4aR4b, —N═CR4aR4b, —N(R4)—C(═Z)R4, —N(R4)—C(═Z)NR4aR4b, —S(O)NR4aR4b, —S(O)2NR4aR4b, —N(R4)—S(═O)R4, —N(R4)—S(═O)2R4, —OR4, —SR4, and —OC(═OZ)R4, wherein each R4, R4a and R4b is separately selected from the groups defined below;
• or
• two R2a, R2b, R2c and R2d on adjacent carbons taken together with the two intervening carbons to which they are attached, form a C3-6 cycloalkenyl, aryl, heteroaryl or C2-6 heterocycloalkyl group;
• R3 is selected from the group consisting of hydrogen, OR4, C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, halogen, —CN, —SR4, sulfonyl, —NR4aR4b, and C1-6 haloalkyl, wherein R4, R4a and R4b are selected from the groups defined below;
• R4, R4a and R4b are separately selected from the group consisting of hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, aryl, heteroaryl, C2-6 heterocycloalkyl;
• or
• R4a and R4b taken together with the nitrogen to which they are attached, form a C2-6 heterocycloalkyl group;
• or
• R4a and R4b taken together with the carbon to which they are attached, form a C3-6 cycloalkyl or C2-6 heterocycloalkyl group;
• Z is O (oxygen) or S (sulfur), and
• wherein each of said alkyl, alkenyl, alkynyl, cycloalkyl, alkoxy cycloalkenyl, aryl, heteroaryl and C2-6 heterocycloalkyl independently is optionally substituted by one or more substituent(s) independently selected from the group consisting of —CN, halogen, haloalkyl, —O(C1-6 alkyl), —NR4aR4b, —S(C1-6 alkyl), —O(C1-6 haloalkyl).