RSV antiviral pyrazolo- and triazolo-pyrimidine compounds

A compound of formula (I)

• and any stereochemically isomeric form thereof, wherein
• X is N or CR6 wherein R6 is hydrogen, halo or C1-4alkyl;
• R1 is CH3 or CH2CH3, and R1′ is hydrogen;
• or R1 and R1′ are taken together with the carbon atom to which they are attached to form cyclopropyl;
• and R2 is C3-6alkyl and R3 is C1-4alkyl;
• or the
• moiety is a radical of formula:
• wherein R1 is CH3 or CH2CH3, and R1′ is hydrogen;
• or R1′ is absent in radical (a-6);
• or R1 and R1′ are taken together with the carbon atom to which they are attached to form cyclopropyl;
• and radical (a-1) to (a-30) are optionally substituted with one or two substituents each independently selected from C1-2alkyl and halo;
• R4 is C1-6alkyl;
• C3-6alkenyl, polyhaloC1-4alkyl;
• C1-4alkyl substituted with one C3-6cycloalkyl;
• aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyl;
• oxetanyl optionally substituted with C1-4alkyl;
• Heteroaryl1;
• C3-6cycloalkyl;
• C3-6cycloalkyl substituted with one or two substituents each individually selected from hydroxy, halo, cyano, C1-4alkyl, C1-4alkyloxy, polyhaloC1-4alkyl, and polyhaloC1-4alkyloxy;
• or
• NR7R8 wherein R7 is selected from hydrogen and C1-4alkyl;
• R8 is C1-4alkyl or C3-6cycloalkyl;
• or R7 and R8 are taken together with the nitrogen to which they are attached to form azetidinyl, pyrrolidinyl or piperidinyl;
• R5 is C3-6cycloalkyl;
• Heteroaryl;
• Bicycle;
• naphthyl substituted with 1, 2 or 3 substituents each independently selected from halo and hydroxycarbonyl;
• phenyl substituted with 1, 2 or 3 substituents each independently selected from
• hydroxy;
• halo;
• C1-6alkyl;
• C1-6alkyl substituted with one, two or three substituents each independently selected from halo, hydroxy, hydroxycarbonyl, aminocarbonyl, Heterocycle, C3-6cycloalkyl, C3-6cycloalkyl substituted with one or two substituents each independently selected from C1-4alkyl, halo, hydroxycarbonyl, and C1-4alkyl substituted with hydroxycarbonyl;
• C3-6alkenyl;
• C3-6alkenyl substituted with one or two substituents selected from C1-6alkyl, hydroxy, hydroxycarbonyl and aminocarbonyl;
• C3-6alkynyl;
• C3-6alkynyl substituted with one hydroxycarbonyl;
• C3-6cycloalkyl;
• C3-6cycloalkyl substituted with one, two or three substituents each independently selected from C1-4alkyl, halo, hydroxycarbonyl, and C1-4alkyl substituted with hydroxycarbonyl;
• C3-6cycloalkenyl;
• C3-6cycloalkenyl substituted with one hydroxycarbonyl;
• C1-6alkyloxy optionally substituted with hydroxycarbonyl;
• polyhaloC1-4alkyl;
• polyhaloC1-4alkyloxy;
• cyano;
• nitro;
• B(OH)2;
• hydroxycarbonyl;
• CO—NHOH;
• CO—NR9R10;
• CO—NH—NR9R10;
• NR9R10;
• NH—CO—R11;
• NH—CO—O—R11;
• NH—CO—NH—R11;
• NH—CS—NH—R11;
• NH—C═(N—CN)—NH—R11;
• aminosulfonyl;
• mono- or di(C1-4alkyl)aminosulfonyl;
• Heterocycle;
• and
• spiro[3.3]heptanyl optionally substituted with hydroxycarbonyl;
• wherein
• R9 and R10 are each independently selected from hydrogen;
• C1-6alkyl;
• SO2—R12;
• and C1-6alkyl substituted with one or two substituents each independently selected from hydroxy, hydroxycarbonyl, C3-6cycloalkyl, C3-6cycloalkyl substituted with hydroxycarbonyl, C1-4alkylcarbonylamino, mono- or di(C1-4alkyl)amino, and Heterocycle;
• R11 is C1-6alkyl;
• C3-6alkenyl;
• C3-6cycloalkyl;
• Aryl;
• Heterocycle;
• or C1-6alkyl substituted with one substituent selected from C3-6cycloalkyl, C1-4alkyloxy, hydroxy, cyano, hydroxycarbonyl, aminocarbonyl, mono- or di(C1-4alkyl)aminocarbonyl, C1-4alkylcarbonylamino, and Heterocycle;
• R12 is C1-4alkyl, C3-6cycloalkyl, or C1-4alkyl substituted with one C3-6cycloalkyl,
• Heteroaryl is thienyl, imidazolyl, pyrazolyl, thiazolyl, pyridinyl, 1-benzopyrazolyl, 2,3-dihydro-1H-indolyl, 2-oxo-2,3-dihydro-1H-indolyl, quinolinyl, 2-oxo-quinolinyl, benzimidazolyl, cinnolinyl, or 2H-chromenyl, wherein each Heteroaryl is optionally substituted with one or two substituents each independently selected from C1-4alkyl, halo, amino, aminocarbonyl, and NH—CO—C3-6cycloalkyl;
• Heteroaryl1 is imidazolyl or pyrazolyl;
• wherein each Heteroaryl1 is optionally substituted with one or two substituents each independently selected from C1-4alkyl, halo and hydroxycarbonyl;
• Heterocycle is azetidinyl, tetrahydrofuranyl, pyrrolidinyl, furanyl, thienyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, isoxazolyl, 1,2,4-oxadiazolyl, 2,5-dihydro-1H-pyrrolyl, pyridinyl, pyrimidinyl, pyrazinyl, 2-oxo-azepanyl, 2,5-dioxopyrrolidinyl, or 3-oxo-2,3-dihydro-1,2-oxazolyl;
• wherein each Heterocycle is optionally substituted with one or two substituents each independently selected from C1-4alkyl, C3-6cycloalkyl, halo, hydroxyC1-4alkyl, polyhaloC1-4alkyl, hydroxycarbonyl, and C1-4alkyl substituted with hydroxycarbonyl;
• Aryl is phenyl substituted with one or two substituents each independently selected from hydrogen, halogen, C1-4alkyl, C1-4alkyloxy, and trifluoromethyl;
• Bicycle is 1,2,3,4-tetrahydronaphthalenyl, chromanyl or 2,3-dihydrobenzofuranyl;
• wherein each Bicycle is optionally substituted with one or two substituents each independently selected from C1-4alkyl, halo and hydroxycarbonyl;
• with the proviso that [7-ethyl-2-(3-thienyl)pyrazolo[1,5-a]pyrimidin-5-yl] (2-methyl-1-piperidinyl)-methanone and [7-ethyl-2-(2-pyridinyl)pyrazolo[1,5-a]pyrimidin-5-yl](2-methyl-1-piperidinyl)-methanone are not included;
• or a pharmaceutically acceptable acid addition salt thereof.