Inhibitors of respiratory syncytial virus

A method of inhibiting replication of respiratory syncytial virus in a sample, comprising contacting the sample with an effective amount of a compound of formula (I):

• wherein:
• A and B are each independently aryl, heteroaryl, cycloalkyl or heterocycle;
• n is 0, 1, 2, 3, 4 or 5;
• R1 is selected from the group consisting of alkyl, halo, nitro, cyano, haloalkyl, amino, alkoxy, —SO2H, —SO2NHR′, CONHR′, aryl, heteroaryl, cycloalkyl and heterocycle;
• each R′ is independently selected from the group consisting of hydrogen and alkyl;
• X is a bond, —C(O)—, CH2 and SO2;
• R2 and R3 are independently selected from the group consisting of hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocycle, haloalkyl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, alkoxyalkyl and aminoalkyl, or R2 and R3 are taken together with the atom to which they are attached to form a heterocyclic ring;
• each aryl is independently selected from the group consisting of phenyl, naphthyl and anthracenyl;
• each heteroaryl is independently an aromatic 5-8 membered monocyclic ring having 1-3 heteroatoms, an 8-12 membered bicyclic ring having 1-6 heteroatoms, or an aromatic 11-14 membered tricyclic ring system having 1-9 heteroatoms, said heteroatoms each independently selected from the group consisting of O, N, S, P and Si;
• each cycloalkyl is independently a non-aromatic, saturated or partially unsaturated cyclic, bicyclic or tricyclic hydrocarbon group having 3 to 12 carbon atoms;
• and
• each heterocycle is independently:
• a nonaromatic, saturated or partially unsaturated 3-10 membered monocyclic ring system having 1-3 heteroatoms;
• a nonaromatic, saturated or partially unsaturated 8-12 membered bicyclic ring system having 1-6 heteroatoms;
• or a nonaromatic, saturated or partially unsaturated tricyclic ring system having 1-9 heteroatoms;
• said heteroatoms each independently selected from the group consisting of O, N, S, P and Si.

A pharmaceutical composition comprising a compound of formula (I) and a pharmaceutically acceptable carrier:

• wherein:
• A and B are each independently aryl, heteroaryl, cycloalkyl or heterocycle;
• n is 0, 1, 2, 3, 4 or 5;
• R1 is selected from the group consisting of alkyl, halo, nitro, cyano, haloalkyl, amino, alkoxy, —SO2H, —SO2NHR′, CONHR′, aryl, heteroaryl, cycloalkyl and heterocycle;
• each R′ is independently selected from the group consisting of hydrogen and alkyl;
• X is a bond, —C(O)—, CH2 and SO2;
• R2 and R3 are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, heterocycloalkyl, alkoxyalkyl and aminoalkyl, or R2 and R3 are taken together with the atom to which they are attached to form a heterocyclic ring;
• each aryl is independently selected from the group consisting of phenyl, naphthyl and anthracenyl;
• each heteroaryl is independently an aromatic 5-8 membered monocyclic ring having 1-3 heteroatoms, an 8-12 membered bicyclic ring having 1-6 heteroatoms, or an aromatic 11-14 membered tricyclic ring system having 1-9 heteroatoms, said heteroatoms each independently selected from the group consisting of O, N, S, P and Si;
• each cycloalkyl is independently a non-aromatic, saturated or partially unsaturated cyclic, bicyclic or tricyclic hydrocarbon group having 3 to 12 carbon atoms;
• and
• each heterocycle is independently:
• a nonaromatic, saturated or partially unsaturated 3-10 membered monocyclic ring system having 1-3 heteroatoms;
• a nonaromatic, saturated or partially unsaturated 8-12 membered bicyclic ring system having 1-6 heteroatoms;
• or a nonaromatic, saturated or partially unsaturated tricyclic ring system having 1-9 heteroatoms;
• said heteroatoms each independently selected from the group consisting of O, N, S, P and Si.

A compound of formula (III):

• wherein:
• A and B are each independently aryl, heteroaryl, cycloalkyl or heterocycle;
• n is 0, 1, 2, 3, 4 or 5;
• R1 is selected from the group consisting of C2-C6 alkyl, halo, cyano, haloalkyl, amino, alkoxy, —SO2H, —SO2NHR′, CONHR′, aryl, heteroaryl, cycloalkyl and heterocycle;
• each R′ is independently selected from the group consisting of hydrogen and alkyl;
• X is a bond, —C(O)—, CH2 and SO2;
• R2 and R3 are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, heterocycloalkyl, alkoxyalkyl and aminoalkyl, or R2 and R3 are taken together with the atom to which they are attached to form a heterocyclic ring;
• each aryl is independently selected from the group consisting of phenyl, naphthyl and anthracenyl;
• each heteroaryl is independently an aromatic 5-8 membered monocyclic ring having 1-3 heteroatoms, an 8-12 membered bicyclic ring having 1-6 heteroatoms, or an aromatic 11-14 membered tricyclic ring system having 1-9 heteroatoms, said heteroatoms each independently selected from the group consisting of O, N, S, P and Si;
• each cycloalkyl is independently a non-aromatic, saturated or partially unsaturated cyclic, bicyclic or tricyclic hydrocarbon group having 3 to 12 carbon atoms;
• and
• each heterocycle is independently:
• a nonaromatic, saturated or partially unsaturated 3-10 membered monocyclic ring system having 1-3 heteroatoms;
• a nonaromatic, saturated or partially unsaturated 8-12 membered bicyclic ring system having 1-6 heteroatoms;
• or a nonaromatic, saturated or partially unsaturated tricyclic ring system having 1-9 heteroatoms;
• said heteroatoms each independently selected from the group consisting of O, N, S, P and Si.

A compound selected from the group consisting of:

• 4-((1-(4-isopropylbenzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)-N-(3-methoxypropyl)benzamide;
• 4-((1-(4-bromobenzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)-N-(3-methoxypropyl)benzamide;
• 4-((1-(4-ethylbenzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)-N-(3-methoxypropyl)benzamide;
• 4-((1-(4-methylbenzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)-N-(oxetan-3-ylmethyl)benzamide;
• and
• 4-((1-(4-(dimethylamino)benzyl)-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)methyl)-N-(oxetan-3-ylmethyl)benzamide.