2-substituted benzimidazoles as selective androgen receptor modulators (SARMS)

A compound of formula (I)

• wherein
• R1 is selected from the group consisting of —(CH2)—(C2-4alkenyl), —(CH2)—(C2-4alkynyl), fluorinated lower alkyl, -(lower alkyl)-CN, —(CH2)-heteroaryl, —(CH2)-aryl, —SO2—(lower alkyl), —SO2— (phenyl), —SO2— (tolyl), —(CH2)-(fluorinated lower alkyl), -(lower alkyl)-C(O)—O-(lower alkyl), -(lower alkyl)-O-(lower alkyl), -(lower alkyl)-S(O)0-2-(lower alkyl) and -(lower alkyl)-O—Si(CH3)2(t-butyl);
• R2 and R3 are each independently selected from the group consisting of halogen, hydroxy, carboxy, lower alkyl, halogen substituted lower alkyl, lower alkoxy, halogen substituted lower alkoxy, cyano, nitro, amino, lower alkylamino, di(lower alkyl)amino, —C(O)-(lower alkyl), —C(O)-(lower alkoxy), —C(O)—NRARB, —S(O)0-2-(lower alkyl), —SO2—NRARB, —N(RA)—C(O)-(lower alkyl) and —N(RA)—C(O)-(halogen substituted lower alkyl);
• wherein each RA and RB is independently selected from hydrogen or lower alkyl;
• R4 is selected from the group consisting of alkenyl, alkynyl, aryl, —(C2-4alkyl)-aryl, heteroaryl and —(C2-4alkyl)-heteroaryl;
• wherein the alkenyl or alkynyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, carboxy, cyano, nitro, NRERF, NRE—C(O)-lower alkyl and phenyl;
• wherein RE and RF are each independently selected from hydrogen or lower alkyl;
• and wherein the phenyl is optionally substituted with one to four substituents independently selected from the group consisting of halogen, lower alkyl, lower alkoxy, hydroxy, carboxy, cyano, nitro, amino, (lower alkyl)amino and di(lower alkyl)amino;
• wherein the aryl or heteroaryl, whether alone or as part of a substituent group is optionally substituted with one or more substituents independently selected from the group consisting of halogen, hydroxy, carboxy, lower alkyl, lower alkoxy, fluorinated lower alkyl, fluorinated lower alkoxy, phenoxy, cyano, nitro, NRCRD and -(lower alkyl)-NRBRC, —C(O)-(lower alkyl), —C(O)-(lower alkoxy), —C(O)—NRCRD, —N(RC)—C(O)-(lower alkyl), —N(RC)—C(O)-(halogen substituted lower alkyl), —S(O)0-2-(lower alkyl) and —SO2—NRCRD;
• wherein each RC and RD is independently selected from hydrogen or lower alkyl;
• R5 is OR6;
• wherein R6 is selected from the group consisting of hydrogen, lower alkyl and —C(O)-(lower alkyl);
• alternatively, R4 and R5 are taken together with the atom to which they are bound to form a ring structure selected from the group consisting of 2-pyrrolidinyl, 2-tetrahydro-furanyl, 2-(2,5-dihydro-1H-pyrrolyl), 2-(2,5-dihydro-furanyl), 2-imidazolidinyl, 2-oxazolidinyl, 2-[1,3]dioxolanyl, 2-piperidinyl, 6-(1,2,3,6-tetrahydro-pyridinyl), 2-(1,2,3,6-tetrahydro-pyridinyl), 2-tetrahydropyranyl, 6-(3,6-dihydro-2H-pyranyl), 2-(3,6-dihydro-2H-pyranyl), 2-(hexahydro-pyrimidinyl), 2-[1,3]oxazinanyl and 2-[1,3]dioxanyl;
• wherein the ring structure is optionally substituted with one or more substituents independently selected from the group consisting of lower alkyl, -(lower alkyl)-OH and -(lower alkyl)-(halogen);
• and pharmaceutically acceptable salts thereof.