Compounds and methods which modulate feeding behavior and related diseases

A compound of formula

• or a pharmaceutically acceptable salt thereof, wherein Y is C(R6);
• A is N—H;
• R6 is a hydrogen, —OH, halo, —CF3, —OCF3, (C1-C8)alkoxy, aryl, —NH2, —NH((C1-C8)alkyl), —N((C1-C8)alkyl)2, (C1-C8)alkyl, (C3-C10)cycloalkyl or —Z(Q) radical;
• R1 is a hydrogen, halo, —OH, —NO2, —NHOH, —CF3, —OCF3, (C1-C8)alkyl, (C3-C10)cycloalkyl, —Z((C1-C8)alkoxy), —Z(aryloxy), —Z(aryl), —Z(heteroaryl), —Z((C3-C10)cycloalkyl), —Z(NR5SO2R5), —Z(CON(R5)2), —Z(CO2R5), —Z(N(R5)2), —Z(NR5CON(R5)2), —Z(NR5 (CO)R5), —Z(NR5CO2R5), —Z(COR5), —Z(S(O)pR5) or —Z(Q) radical;
• R2 is a hydrogen, halo, —OH, —NO2, —CF3, —OCF3, (C1-C8)alkyl, (C3-C10)cycloalkyl, —Z((C1-C8)alkoxy), —Z(aryloxy), —Z(aryl), —Z(heteroaryl), —Z((C3-C10)cycloalkyl), —Z(NR5SO2R5), —Z(CON(R5)2), —Z(CO2R5), —Z(N(R5)2), —Z(NR5CON(R5)2), —Z(NR5 (CO)R5), —Z(NR5CO2R5), —Z(COR5), —Z(S(O)pR5) or —Z(Q) radical, provided that R2 is not an optionally substituted phenyl, pyridyl, pyrazinyl, pyrimidyl or pyridazinyl radical;
• R3 is a (C3-C10)cycloalkyl, (C1-C8)alkyl, —(C1-C8)alkyl)OH, (C1-C8)alkoxy-(C1-C8)alkyl-, —((C1-C8)alkyl)N(R5)2, —((C1-C8)alkyl)S(O)p ((C1-C8)alkyl), —(CH2)((C3-C10)cycloalkyl)k (CH2)mOH, —(CH2)m ((C3-C10)cycloalkyl)(CH2)mOH, —(CH2)m ((C3-C10)cycloalkyl)k (CH2)OH, —(CH2)((C3-C10)cycloalkyl)k (CH2)m (C1-C8)alkoxy, —(CH2)m ((C3-C10)cycloalkyl)(CH2)m (C1-C8)alkoxy, —(CH2)m ((C3-C10)cycloalkyl)k (CH2)(C1-C8)alkoxy, —(CH2)((C3-C10)cycloalkyl)k (CH2)mN(R5)2, —(CH2)m ((C3-C10)cycloalkyl)(CH2)mN(R5)2, —(CH2)m ((C3-C10)cycloalkyl)k (CH2)N(R5)2, —(CH2)m ((C3-C10)cycloalkyl)(CH2)mS(O)pR5, —D′(S(O)qR5), —D′(aryloxy), —D′(aryl), —D′(heteroaryl), —D′((C3-C10)cycloalkyl), —D′(NR5SO2R5), —D′(CON(R5)2), —D′(CO2R5), —D′(NR5CON(R5)2), —D′(NR5 (CO)R5), —D′(NR5CO2R5), —D′(COR5), —D′(Q), —D(aryloxy), —D(aryl), —D(heteroaryl), —D((C3-C10)cycloalkyl), —D(NR5SO2R5), —D(CON(R5)2), —D(CO2R5), —D(S(O)qR5), —D(NR5CON(R5)2), —D(NR5 (CO)R5), —D(NR5CO2R5), —D(COR5) or —(NR5)k—D—Q radical;
• X is a (C1-C8)alkyl, (C3-C10)cycloalkyl, —(NR5)k (C1-C8)alkyl)(C1-C8)alkoxy, —(NR5)k ((C1-C8)alkyl)aryloxy, —(NR5)((C1-C8)alkyl)kS(O)pR5, —(NR5)k ((C1-C8)alkyl)S(O)pR5, —(NR5)D(C1-C8)alkoxy, —(NR5)(CH2)m ((C3-C10)cycloalkyl)k (CH2)(C1-C8)alkoxy, —(NR5)k (CH2)((C3-C10)cycloalkyl)k (CH2)m (C1-C8)alkoxy, —(NR5)k (CH2)m ((C3-C10)cycloalkyl)(CH2)m (C1-C8)alkoxy, —(NR5)(CH2)m ((C3-C10)cycloalkyl)k (CH2)aryloxy, —(NR5)k (CH2)((C3-C10)cycloalkyl)k (CH2)maryloxy, —(NR5)k (CH2)m ((C3-C10)cycloalkyl)(CH2)maryloxy, —Z(S(O)qR5), —Z(aryl), —Z(heteroaryl), —Z((C3-C10)cycloalkyl), —Z(NR5SO2R5), —Z(CON(R5)2), —Z(CO2R5), —Z(N(R5)2), —Z(NR5CON(R5)2), —Z(NR5 (CO)R5), —Z(NR5CO2R5), —Z(COR5) or —Z(Q) radical;
• Q is a 4-membered to 10-membered heterocyclyl or heteroaryl ring optionally substituted with 1-2 radicals of R8;
• wherein each R8 is independently a —OH, halo, —CF3, —OCF3, (C1-C8)alkoxy, —NH2, —NH((C1-C8)alkyl), —N((C1-C8)alkyl)2, or (C1-C8)alkyl radical;
• each R5 is independently a hydrogen, —OH, (C1-C8)alkoxy, aryl, —NH2, —NH((C1-C8)alkyl), —N((C1-C8)alkyl)2, (C1-C8)alkyl or (C3-C10)cycloalkyl radical;
• D is —(CH2)m ((C3-C10)cycloalkyl)k (CH2)m— and D′ is —((C1-C8)alkyl)k—;
• Z is D(NR5)k, D′(NR5)k, (NR5)kD or (NR5)kD′;
• each k is independently 0 or 1;
• each m is independently an integer between 0 and 6;
• each p is independently an integer between 0 and 2;
• and
• each q is independently 1 or 2;
• and
• wherein each alkyl, aryl, heteroaryl, cycloalkyl, Q, alkoxy or aryloxy moiety of any of X, R1, R2, R3, R5, R6 and R8 is optionally substituted with one or more radicals of halo, —CF3, —OCF3, —Z(COOH), —Z(OH), —Z(NO2), —Z(SH), —(C1-C8)alkyl, —(C1-C8)acyloxy, —(C3-C10)cycloalkyl, —S—((C1-C8)alkyl)k-aryl, —((C1-C8)alkyl)k—SO2NH-aryl, —S—(C1-C8)alkyl, —Z((C1-C8)alkoxy), —Z(aryloxy), —Z(aryl), —Z(heteroaryl), —Z((C3-C10)cycloalkyl), —Z(NR9SO2R9), —Z(CON(R9)2), —Z(CO2R9), —Z(N(R9)2), —Z(NR9CON(R9)2), —Z(NR9 (CO)R9), —Z(NR9CO2R9), —Z(COR9), —Z(S(O)pR9) or —Z(Q), wherein each R9 is independently a hydrogen or (C1-C8)alkyl radical and wherein such aryl, heteroaryl, cycloalkyl and Q substituents are optionally substituted with one or more radicals of halo, —NO2, —CF3, —OCF3, —N(R9)2, —C(O)R9, —CO2R9, —OR9, —SR9 or (C1-C8)alkyl;
• and
• provided that the total number of aryl, heteroaryl, cycloalkyl, heterocyclyl and Q moieties in A, X, Y, R1, R2 and R3 is 0-4;
• and
• provided that:
• (a) when R1 is hydrogen, halo, alkyl, cycloalkyl, alkoxy or alkylthio, then (1) when R3 is methyl and R2 is acetyl or —COOCH3, X is not NH2 or trifluoromethylphenyl;
• (2) when R3 is methyl or —COOCH2CH3 and R2 is H, X is not methyl;
• and (3) when one of R2, or R3 is optionally substituted -ethyl-NR5CONHR5, X is not alkyl or cycloalkyl;
• (b) when A is N—H and R3 is aryl or heteroaryl, then R2 is not aryl or heteroaryl;
• and
• (c) when A is N—H or and R2 is H, then R3 is not optionally substituted phenyl which is substituted by —N(R5)—(C2-C6 alkyl)-N(R5)2 or —N(R5)—(C2-C6 alkyl)—Q.