8-hydroxy-7-substituted quinolines as anti-viral agents

A compound of formula V

• wherein
• R1, R2, and R3 are independently hydrogen;
• X1 is
• a) phenyl substituted by one Cl, I, —CH2OH, ethyl, propyl, ethoxy, —O-benzyl, —O-phenyl, —SO2NH-indazoyl, or NO2;
• b) 2-methylphenyl,
• c) 2-bromophenyl,
• d) phenyl substituted by two substituents wherein one substituent is (Cl, Br, I, methyl or NO2, the other substituent is F, Cl, methyl, NO2, or methoxy;
• e) phenyl substituted by Cl, methyl, and methoxy,
• f) naphthyl substituted by F, Br, Cl, or OH;
• g) fluorenyl
• h) het, or
• i) 4-cyano-2,3,5,6-tetrafluorophenyl;
• and het is
• a) coumarinyl,
• b) indazoyl,
• c) indolyl,
• d) benzothiazolyl,
• e) benzothiadiazolyl, or
• f) quinolinyl.

A compound of formula IA

• wherein R0 is
• a) —(CH2)pW1X2,
• b) —(CH2)pW1CH2X1, or
• c) —(CH2)n—CH9—(CH2)nX1;
• wherein R1 is
• a) —H,
• b) —F,
• c) —Cl,
• d) —Br,
• e) —CF3, or
• f) —NO2;
• wherein R2 is
• a) —H,
• b) —C1-C3alkyl,
• c) —OH,
• d) —CF3,
• e) —CH═CH-furanyl,
• f) —CH═CH-phenyl substituted by zero (0) or one (1) R4,
• g) —CH═CH-pyridinyl,
• h) —(CH2)p-phenyl substituted by zero (0) or one (1) R4,
• i) —NHV1,
• j) —CH2NHV1, or
• k) —CH2Z1;
• wherein R3 is
• a) —H,
• b) —OH,
• c) —CF3, or
• d) —C1-C3alkyl;
• wherein R4 is
• a) —H
• b) —F,
• c) —C1,
• d) —Br,
• e) —NO2,
• f) —CF3,
• g) —W1—R10,
• h) —C1-C6 alkyl,
• i) —C3—C8 cycloalkyl,
• j) —(CH2)n-aryl,
• k) —CH2—C3-C8 cycloalkyl,
• l) —SO2NH-indazoyl,
• m) —CN,
• n) —I, or
• o) —CH2—OH;
• wherein R5 is
• a) —H,
• b) —F,
• c) —Cl,
• d) —Br,
• e) —W1—R10,
• f) —CF3,
• g) —C1-C6 alkyl,
• h) —C3-C8 cycloalkyl,
• i) —(CH2)n-aryl substituted by R6, or
• j) —CH2—C3-C8 cycloalkyl;
• wherein R6 is
• a) —H,
• b) —F,
• c) —Cl, or
• d) —Br;
• wherein R8 is
• a) —C1-C4 alkyl,
• b) —W1—H, or
• c) —CH2W1H;
• wherein R9 is
• a) —C1-C7 alkyl,
• b) —C3-C8 cycloalkyl,
• C) —C(O)R11,
• d) —C(O)NHR11,
• e) —CH(OH)R11,
• f) —CH2OH,
• g) —CO2R11, or
• h) -aryl;
• wherein R10 is
• a) —H,
• b) —C1-C6 alkyl,
• c) —C3-C8 cycloalkyl,
• d) —(CH2)n-aryl optionally substituted with F, Cl, CH2OH or —NO2,
• e) —CH2—C3-C8 cycloalkyl;
• wherein R11 is
• a) —C1-C7 alkyl,
• b) —C3-C8 cycloalkyl,
• c) —(CH2)nX1, or
• d) —CH2—C3-C8 cycloalkyl;
• wherein X1 is
• a) -aryl substituted by zero (0), one (1), two (2), or three (3) R4,
• b) -het substituted by zero (0), one (1) or two (2) R5,
• c) —C7-C8 alkyl, provided that when X1 is alkyl, R9 is not alkyl;
• d) —CH(OH)-phenyl,
• e) —S-phenyl,
• f) —NHSO2-phenyl substituted by one (1), two (2) or three (3) R4,
• g) —CN,
• h) —C3-C8 cycloalkyl substituted by ethoxy, t-butyl or two (2) R8, or
• i) -4-cyano-2,3,5,6-tetrafluoro-phenyl;
• wherein X2 is
• a) -aryl substituted by zero (0), one (1), two (2) or three (3) R4,
• b) —C1-C8 alkyl,
• c) —CH(OH)-phenyl, or
• d) —C3-C8 cycloalkyl substituted by zero (0), one (1) or two (2) R8;
• wherein W1 is
• a) oxygen, provided that when X1 or X2 is phenyl, W1 is not oxygen,
• b) —NH, or
• c) -sulfur,
• wherein V1 is
• a) —R11,
• b) —C(O)R11,
• c) —SO2R11, or
• d) —C(O)NHR11;
• wherein Z1 is
• a) —C1-C7 alkyl,
• b) —C3-C8 cycloalkyl,
• c) —C(O)R11,
• d) —C(O)NHR11, or
• e) —CO2R11;
• wherein -aryl is
• a) -phenyl,
• b) -naphthyl,
• c) -biphenyl,
• d) -tetrahydro-naphthyl, or
• e) fluorenyl;
• wherein -het is a 5-membered saturated or unsaturated ring having from one (1) to three (3) heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur,
• wherein -cycloalkyl is a saturated or unsaturated hydrocarbon ring, optionally fused to a benzene ring;
• wherein n is zero (0) to six (6), inclusive, provided that where X1 is a) or b), n is at least one;
• p is one (1), two (2) or three (3);
• or a pharmaceutically acceptable salt or N-oxide thereof.