Pyrazolo[1,5-a]pyrimidines as antiviral compounds

A compound of formula (Id)

• or a pharmaceutically acceptable salt thereof,
• wherein
• W is
• R1 is H or C1-C6 alkyl,
• each R2 is independently selected from C1-C6 alkyl, R5O—, R6R7NC(O)—, R9C(O)N(R8)—, R10OC(O)—, R11C(O)O—, and halogen;
• R5, R6, R7 and R8 are independently selected from H and C1-C6 alkyl;
• R9, R10 and R11 are independently selected from C1-6 alkyl;
• any alkyl is optionally substituted by one or more F;
• or
• two R2 together form a methylenedioxy or ethylenedioxy biradical;
• R3 is C1-C6 alkyl;
• m is an integer of from 0 to 2;
• each R4 is independently selected from C1-C6 alkyl, R12O, halogen, R13R14NC(O)—, R16C(O)N(R15)—, R17OC(O)—, R18C(O)O—, R19S(O)2—, R20S(O)2N(H)—, NH2S(O)2—, R21C(O)—, N(R22)(R23)—, and —O—;
• R12, R13, R14, R15, R22, and R23 are independently selected from H and C1-C6 alkyl,
• R16, R17, R18, R19, R20, and R21 are independently selected from C1-6 alkyl;
• any alkyl is optionally substituted by one or more F;
• or
• two R4 attached to adjacent atoms of ring B form, together with the atoms to which they are attached, a 5- or 6-membered heterocyclic or carbocyclic ring, or a benzene ring;
• ring B is 5- or 6-membered heteroaryl or phenyl;
• provided that the compound is not:
• N-[(4-chlorophenyl)methyl]-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-[(4-methoxyphenyl)methyl]-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-[2-(4-chlorophenyl)ethyl]-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(p-tolylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(3-phenylpropyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• N-(1,3-benzodioxol-5-ylmethyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-[(4-fluorophenyl)methyl]-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(2-phenylpropyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-[2-(2,4-dimethoxyphenyl)ethyl]-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(2-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• N-benzyl-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-(4-bromophenyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(p-tolyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-(4-methoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(m-tolyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• N-(3-chlorophenyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-(3,4-dimethylphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-(4-fluorophenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-(4-ethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-(3-chloro-4-methyl-phenyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-(3,5-dimethylphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-phenyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-[4-[[3-(3,4-dimethoxy phenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-yl]amino]phenyl]acetamide
• N-(3,4-dichlorophenyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-(4-isopropylphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-(3-methoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine
• 3-(3,4-dimethoxyphenyl)-N-(4-ethylphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-(4-butylphenyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine, or
• N-(3,5-dichlorophenyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine.

A compound of formula (Ih)

• or a pharmaceutically acceptable salt thereof, wherein
• p is an integer of from 1 to 3;
• Z is N or CR2;
• R1 is H or C1-C6 alkyl;
• each R2 is independently selected from C1-C6 alkyl, R5O—, R6R7NC(O)—, R9C(O)N(R8)—, R10OC(O)—, R11C(O)O—, and halogen;
• R5, R6, R7 and R8 are independently selected from H and C1-C6 alkyl;
• R9, R10 and R11 are independently selected from C1-6 alkyl;
• any alkyl is optionally substituted by one or more F;
• or
• two R2 together form a methylenedioxy or ethylenedioxy biradical;
• no R2 is attached in ortho position on the phenyl ring;
• R3 is C1-C6 alkyl;
• m is an integer of from 0 to 2;
• each R4 is independently selected from C1-C6 alkyl, R12O, halogen, R13R14NC(O)—, R16C(O)N(R15)—, R17OC(O)—, R18C(O)O—, R19S(O)2—, R20S(O)2N(H)—, NH2S(O)2—, R21C(O)—, N(R22)(R23)—, and —O—;
• R12, R13, R14, R15, R22, and R23 are independently selected from H and C1-C6 alkyl,
• R16, R17, R18, R19, R20, and R21 are independently selected from C1-6 alkyl;
• any alkyl is optionally substituted by one or more F;
• or
• two R4 attached to adjacent atoms of ring B form, together with the atoms to which they are attached, a 5- or 6-membered heterocyclic or carbocyclic ring, or a benzene ring;
• ring B is 5- or 6-membered heteroaryl or phenyl;
• provided that the compound is not:
• N-benzyl-2,5-dimethyl-3-(p-tolyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(4-methoxyphenyl)-2,5-dimethyl-N-(pyridin-3-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(4-methoxyphenyl)-2,5-dimethyl-N-(pyridin-4-ylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• N-[(4-chlorophenyl)methyl]-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-[(4-methoxyphenyl)methyl]-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(p-tolylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• N-(1,3-benzodioxol-5-ylmethyl)-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-N-[(4-fluorophenyl)methyl]-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-benzyl-3-(4-fluorophenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-benzyl-3-(4-fluorophenyl)-5-methyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• N-benzyl-3-(4-chlorophenyl)-5-methyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 2,5-dimethyl-3-(p-tolyl)-N-(2-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 2,5-dimethyl-3-(p-tolyl)-N-(3-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(2-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(4-fluorophenyl)-2,5-dimethyl-N-(3-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(4-fluorophenyl)-2,5-dimethyl-N-(2-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• N-benzyl-3-(3,4-dimethoxyphenyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(4-chlorophenyl)-2,5-dimethyl-N-(2-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(4-chlorophenyl)-2,5-dimethyl-N-(3-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 3-(4-methoxyphenyl)-2,5-dimethyl-N-(3-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine, or
• 3-(4-methoxyphenyl)-2,5-dimethyl-N-(4-pyridylmethyl)pyrazolo[1,5-a]pyrimidin-7-amine.

A method of treatment of a viral infection, by administration of a therapeutically effective amount of a compound of formula (I)

• or a pharmaceutically acceptable salt thereof, wherein
• W is
• p is an integer of from 0 to 3,
• R1 is H or C1-C6 alkyl,
• ring A is phenyl or 5- or 6-membered heteroaryl;
• when ring A is phenyl, said phenyl is not substituted in ortho position;
• each R2 is independently selected from C1-C6 alkyl, R5O—, R6R7NC(O)—, R9C(O)N(R8)—, R10OC(O)—, R11C(O)O—, and halogen;
• R5, R6, R7 and R8 are independently selected from H and C1-C6 alkyl;
• R9, R10 and R11 are independently selected from C1-6 alkyl;
• any alkyl is optionally substituted by one or more F;
• or
• two R2 attached to adjacent carbon atoms together form a methylenedioxy or ethylenedioxy biradical;
• R3 is C1-C6 alkyl;
• m is an integer of from 0 to 2;
• each R4 is independently selected from C1-C6 alkyl, R12O, halogen, R13R14NC(O)—, R16C(O)N(R15)—, R17OC(O)—, R18C(O)O—, R19S(O)2—, R20S(O)2N(H)—, NH2S(O)2—, R21C(O)—, N(R22)(R23)—, and −O—;
• R12, R13, R14, R15, R22, and R23 are independently selected from H and C1-C6 alkyl,
• R16, R17, R18, R19, R20, and R21 are independently selected from C1-6 alkyl;
• any alkyl is optionally substituted by one or more F;
• or
• two R4 attached to adjacent atoms of ring B form, together with the atoms to which they are attached, a 5- or 6-membered heterocyclic or carbocyclic ring, or a benzene ring;
• ring B is 5- or 6-membered saturated or unsaturated carbocyclyl, 5- or 6-membered heteroaryl, or phenyl;
• to a mammal in need thereof,
• provided that the compound is not:
• N-(cyclohexylmethyl)-2,5-dimethyl-3-(p-tolyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• 2,5-dimethyl-N-phenyl-3-(p-tolyl)pyrazolo[1,5-a]pyrimidin-7-amine,
• N-benzyl-2,5-dimethyl-3-(p-tolyl)pyrazolo[1,5-a]pyrimidin-7-amine, or
• 2,5-dimethyl-N-phenethyl-3-(p-tolyl)pyrazolo[1,5-a]pyrimidin-7-amine.