Selective melanin concentrating hormone-1 (MCH1) receptor antagonists and uses thereof

A method of reducing the body mass of a subject in need of such reduction, which comprises administering to the subject an amount of a compound effective to reduce the body mass of the subject wherein the compound has the structure:

• wherein A is
• wherein each of Y1, Y2, Y3, Y4 and Y5 is independently —H;
• straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• —F, —Cl, —Br, or —I, NO2;
• —N3;
• —CN;
• —OR3, —OCOR3, —COR3, —CON(R3)2, or —COOR3;
• or any two of Y1, Y2, Y3, Y4 and Y5 present on adjacent carbon atoms can constitute a methylenedioxy group;
• wherein each X is independently S;
• O;
• or NR3;
• wherein R1 is —H;
• —NO2;
• —CN;
• straight chained or branched C1-C7alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• —N(R3)2;
• —OR3;
• —(CH2)pOR3;
• —COR3;
• —CO2R3;
• —CON(R3)2;
• or —CO2(CH2)nV;
• wherein R2 is —H;
• straight chained or branched C1-C7 alkyl, hydroxyalkyl, alkoxyalkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• C3-C10 cycloalkyl-C1-C10 alkyl, C2-C10 cycloalkyl-C1-C10-monofluoroalkyl or C3-C10 cycloalkyl-C1-C10-polyfluoroalkyl;
• —CN;
• —CH2XR3, CH2X(CH2)pNHR3, —(CH2)nNHR3, —CH2X(CH2)pN(R3)2, —CH2X(CH2)pN3, or —CH2X(CH2)pNHCXR7;
• —OR3;
• or wherein R2 and R3 together form a lactone ring;
• wherein each R3 is independently —H;
• straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• wherein R4 is
• wherein the dashed line represents a single bond or a double bond;
• wherein each R is independently —H;
• —F;
• straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• —N(R3)2;
• —NO2;
• —CN;
• —CO2R3;
• —OR or —CON(R3)2;
• wherein each V is independently aryl or heteroaryl, optionally substituted with one or more F;
• Cl;
• Br;
• I;
• COR3;
• CO2R3;
• —CON(R3)2;
• CN;
• —NO2;
• —N(R3)2;
• —OR3;
• —SR3;
• (CH2)qOR3;
• (CH2)qSR3;
• straight chained or branched C1-C7 alkyl, monofluoroalkyl, polyfluoroalkyl, aminoalkyl, or carboxamidoalkyl;
• straight chained or branched C2-C7 alkenyl, C2-C7 alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• wherein each R5 is —H;
• —NO2;
• —N3;
• —CN;
• straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3—C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• —N(R3)2;
• —OR3;
• —(CH2)pOR3;
• —COR3;
• —CO2R3;
• CON(R3)2;
• aryl or heteroaryl, wherein the aryl or heteroaryl is optionally substituted with one or more F;
• Cl;
• Br;
• I;
• COR3;
• CO2R3;
• —CON(R3)2;
• CN;
• —NO2;
• —N(R3)2;
• —OR3;
• —SR3;
• (CH2)qOR3;
• (CH2)qSR3;
• straight chained or branched C1-C7 alkyl, monofluoroalkyl, polyfluoroalkyl, aminoalkyl, or carboxamidoalkyl;
• straight chained or branched C2-C7 alkenyl, C2-C7 alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• wherein R6 is —H;
• straight chained or branched C3-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2∫C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• —N(R3)2;
• —OR3;
• —(CH2)pOR3;
• —COR3;
• —CO2R3;
• —CON(R3)2;
• aryl or heteroaryl, optionally substituted with one or more F;
• Cl;
• Br;
• I;
• COR3;
• CO2R3;
• —CON(R3)2;
• CN;
• —NO2;
• —N(R3)2;
• —OR3;
• —SR3;
• (CH2)qOR3;
• (CH2)qSR3;
• straight chained or branched C3-C7 alkyl, monofluoroalkyl, polyfluoroalkyl, aminoalkyl, or carboxamidoalkyl;
• straight chained or branched C2-C7 alkenyl, C2-C7 alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• wherein R7 is H;
• F;
• CL;
• Br;
• I;
• —NO2;
• —N3;
• —CN;
• straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• —N(R3)2;
• —OR3;
• —(CH2)pOR3;
• —COR3;
• CO2R3;
• or —CON(R3)2;
• wherein R8 is independently straight chained or branched C1-C7 alkyl, monofluoroalkyl or polyfluoroalkyl;
• straight chained or branched C2-C7 alkenyl or alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;
• wherein Z is naphthyl, quinolinyl, isoquinolinyl, quinazoliflyl, phthalazinyl, quinoxalinyl, indolyl, benzo[b]furaflyl, or benzo[b]thiopheflyl;
• wherein the naphthyl, quinolinyl, isoquinolinyl, quinazolinyl, phthalazinyl, quinoxalinyl, indolyl, benzo[b]furanyl, or benzo[b]thiopheflyl may be substituted with one or more F;
• Cl;
• Br;
• I;
• COR3;
• CO2R3;
• —CON(R3)2;
• CN;
• -—NO2;
• —N(R3)2;
• —OR3;
• —SR3;
• (CH2)qOR3;
• (CH2)qSR3;
• straight chained or branched C1-C3 alkyl, monofluoroalkyl, polyfluoroalkyl, aminoalkyl, or carboxamidoalkyl;
• straight chained or branched C2-C7 alkenyl, C2-C7 alkynyl;
• C3-C7 cycloalkyl, monofluorocycloalkyl, polyfluorocyclOalkYl or cycloalkenyl;
• wherein each m is independently an integer from 0 to 3 inclusive;
• wherein each n is independently an integer from 0 to 5 inclusive;
• wherein each p is independently an integer from 1 to 7 inclusive;
• wherein q is an integer from 1 to 3 inclusive;
• wherein r is an integer from 0 to 3 inclusive;
• wherein t is an integer from 2 to 6 inclusiver
• or a pharmaceutically acceptable salt thereof.