Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases

An anti-viral compound having the formula:

• wherein:
• R1′ represents a radical selected from the group consisting of
• —NR5R6, —SO2NR7R8, hydroxyalkyl, hydroxyalkoxy, polyhydroxyalkyl, alkoxyalkoxy, polyfluoroalkyl, dialkylaminoalkyl, R9, —OR9,
• and HET;
• n being an integer from 1 to 4;
• R2 and R3 are each independently selected from the group consisting of straight or branched chain alkyl and hydrogen;
• R4 is a radical selected from the group consisting of a substituted or unsubstituted phenyl radical, an unsubstituted or substituted heterocyclic radical, and —NR12R13;
• R5 and R7 are independently selected from the group consisting of alkoxyalkyl, hydroxyalkyl, polyhydroxyalkyl, aralkyl, R9, —(C═O)R14 and —(C═O)R9;
• R6, R8, R12, and R13 are independently selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, polyfluoroalkyl, hydroxyalkyl, polyhydroxyalkyl, aralkyl, R9, —(C═O)R15 and —(C═O)R9;
• or R5 and R6 taken together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic radical, said heterocyclic radical optionally containing one to two additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or R7 and R8 taken together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic radical, said heterocyclic radical optionally containing one to two additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• said phenyl and heterocyclic radical substituents being at least one selected from the group consisting of alkyl, amino, hydroxy, carbonyl, monoalkylamino, dialkylamino, halogen, and alkoxy;
• R9 is a radical of the formula —W—O(C═O)—CH3, W being a straight- or branched-chain alkylene group of 1 to 6 carbon atoms;
• R10 and R11 are radicals independently selected from the group consisting of alkyl, halo, haloalkyl, and polyfluoroalkyl;
• HET represents an unsubstituted or substituted five to seven membered heterocyclic ring containing one to four heteroatoms independently selected from nitrogen, oxygen or sulfur, wherein the point of attachment to the heterocyclic ring is other than at a nitrogen atom, said heterocyclic ring substituents being one or more radicals selected from the group consisting of alkyl, amino, hydroxy, carbonyl, oxo, monoalkylamino, and dialkylamino, and wherein HET is other that pyridine when R1′ is in the 4- position.
• R14 is a hydroxyalkyl, alkoxyalkyl or cycloalkyl group;
• R15 is an alkyl, hydroxyalkyl, alkoxyalkyl or cycloalkyl group;
• and prodrugs and pharmaceutically acceptable salts of said compound.

An anti-viral compound having the formula:

• wherein Rb is selected from the group consisting of —CH2OCH3, —CH2OCH2CH3, —CH(CH3) OCH2CH3, —CH2—OCH2CH2—OCH3,
• —CH2—OCH2CH2—Si(CH3)3, —CH3, —CH2C6H5, —(CH2)2Si(CH3)3, —CON(RcRd)2, —CSN(RcRd)2, and —PO(NRcRd)2;
• Rc and Rd are independently selected from an alkyl group;
• R1″ represents a radical selected from the group consisting of
• —NR5R6, —SO2NR7R8, hydroxyalkyl, hydroxyalkoxy, polyhydroxyalkyl, alkoxyalkoxy, polyfluoroalkyl, dialkylaminoalkyl, R9, —OR9,
• and HET;
• n being an integer from 1 to 4;
• R2 and R3 are each independently selected from the group consisting of straight or branched chain alkyl and hydrogen;
• R4 is a radical selected from the group consisting of a substituted or unsubstituted phenyl radical, an unsubstituted or substituted heterocyclic radical, and —NR12R13;
• R5 and R7 are independently selected from the group consisting of alkoxyalkyl, hydroxyalkyl, polyhydroxyalkyl, aralkyl, R9, —(C═O)R14 and —(C═O)R9;
• R6, R8, R12, and R13 are independently selected from the group consisting of hydrogen, alkyl, alkoxyalkyl, polyfluoroalkyl, hydroxyalkyl, polyhydroxyalkyl, aralkyl, R9, —(C═O)R15 and —(C═O)R9;
• or R5 and R6 taken together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic radical, said heterocyclic radical optionally containing one to two additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• or R7 and R8 taken together with the nitrogen to which they are attached form a substituted or unsubstituted heterocyclic radical, said heterocyclic radical optionally containing one to two additional heteroatoms independently selected from the group consisting of nitrogen, oxygen, and sulfur;
• said phenyl and heterocyclic radical substituents being at least one selected from the group consisting of alkyl, amino, hydroxy, carbonyl, monoalkylamino, dialkylamino, halogen, and alkoxy;
• R9 is a radical of the formula —W—O(C═O)—CH3, W being a straight- or branched-chain alkylene group of 1 to 6 carbon atoms;
• R10 and R11 are radicals independently selected from the group consisting of alkyl, halo, haloalkyl, and polyfluoroalkyl;
• HET represents an unsubstituted or substituted five to seven membered heterocyclic ring containing one to four heteroatoms independently selected from nitrogen, oxygen or sulfur, wherein the point of attachment to the heterocyclic ring is other than at a nitrogen atom, said heterocyclic ring substituents being one or more radicals selected from the group consisting of alkyl, amino, hydroxy, carbonyl, oxo, monoalkylamino, and dialkylamino, and wherein HET is other than pyridine when R1″ is in the 4- position;
• R14 is a hydroxyalkyl, alkoxyalkyl or cycloalkyl group;
• R15 is an alkyl, hydroxyalkyl, alkoxyalkyl or cycloalkyl group;
• P is a protected formaldehyde group selected from the group consisting of
• wherein R16, R17, R18 and R19 are independently selected from the group consisting of hydrogen and alkyl;
• and prodrugs, isomers and pharmaceutically acceptable salts of said compound.