NEUROACTIVE SUBSTITUTED CYCLOPENT[a]ANTHRACENES AS MODULATORS FOR GABA TYPE-A RECEPTORS

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof;
• wherein:
• R1 is H, ═O, ═CHCN, ═CHCO2Rz, where Rz is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-CN, β-OH, β-ORy, where Ry is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-NO2, spiroepoxy, or C(O)Rx, where Rx is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R2 is H, ═O, ═CHCN, ═CHCO2Rw, where Rw is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-CN, β-OH, β-ORv, where Rv is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-NO2, spiroepoxy, or C(O)Ru, where Ru is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R3 is H, ═O, ═CHCN, ═CHCO2Rt, where Rt is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, —CN, β-OH, β-ORs, where Rs is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl, β-NO2, spiroepoxy, or C(O)Rr, where Rr is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R4 is H, optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R5 is H, ═O, NH(CH3)2, NH(CH2CH3)2, CH2N(CH3)2, CH2N(CH2CH3)2, CO2Rq, where Rq is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, CH2ORp, where Rp is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, C(O)Ro, where Ro is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, C(O)NHRn, where Rn is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, CH2NHRm, where Rm is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, or ORl where Rl is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl;
• R6 is H, optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R7 is H, optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, or optionally substituted C2-C4 alkynyl;
• R8 is H, optionally substituted morpholinyl, or ORk, where Rk is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl;
• R9 is H, optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl;
• R10 is H, CH2N(CH3)2, CH2N(CH2CH3)2, CO2Rj, where Rj is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, CH2ORi, where Ri is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, C(O)Rh, where Rh is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, C(O)NHRg, where Rg is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl, or CH2NHRf, where Rf is optionally substituted C1-C4 alkyl, optionally substituted C2-C4 alkenyl, optionally substituted C2-C4 alkynyl, or optionally substituted aryl,
• R11 is H or C(O)Re, where Re is optionally substituted C1-C20 alkyl, optionally substituted C2-C20 alkenyl, or optionally substituted C2-C20 alkynyl;
• and,
• - - - denotes an optional, additional C—C bond, resulting in either a C═C bond between, C1-C2, C2-C3, C6-C6a, C6a-C7, or C9-C10, with the provisos that when present between:
• (i) C6a-C7, R7 is not present;
• (ii) C6-C6a, R7 is not present and either R5 or R6 is not present, and, when present, R5 is other than ═O;
• (iii) C1-C2, R1 is other than ═O, ═CHCN or ═CHCO2Rz, and R2 is other than ═O, ═CHCN or ═CHCO2Rw;
• and, (iv) C2-C3, R2 is other than ═O, ═CHCN or ═CHCO2Rw, and R3 is other than ═O, ═CHCN or ═CHCO2Rt.