2,6-dimethyl-n-((pyridin-4-yl)methyl)imidazo[1,2-b]pyridazin-8-amine and 2,5-dimethyl-n-[(pyridin-4-yl)methyl]pyrazolo[1,5-a]pyrimidin-7-amine derivatives for treating viral infections
Inventors
Assignees
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Publication Number
US-12319696-B2
Publication Date
2025-06-03
Expiration Date
Abstract
A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein one of X and Y is O and the other one is N; R1 is selected from halogen, CN, NH(CH3), N(CH3)2, C1-C4 alkoxy wherein the alkyl moiety of the C1-C4 alkoxy is optionally substituted by 1-3 halogens, and C1-C4 alkyl, wherein the C1-C4 alkyl is optionally substituted by 1-3 halogens, CN, NH(CH3), or N(CH3)2; and R2 is 3,4-dimethoxyphenyl or 1,3-dimethyl-1H-indazol-5-yl.
Core Innovation
The invention relates to pyrazolo[1,5-a]pyrimidin-7-amine derivatives of formula (I) or pharmaceutically acceptable salts thereof. In formula (I), one of X and Y is C and the other one is N, R1 is selected from fluoro and methyl, and R2 is 3,4-dimethoxyphenyl or 1,3-dimethyl-1H-indazol-5-yl.
The compounds are described for antiviral activity, including treatment of viral infection, RNA viral infection, and particularly non-enveloped single-stranded (+) RNA viruses. Therapeutic use is emphasized for enteroviral infection and picornaviruses, including in vitro antiviral inhibition across picornaviruses such as EV6, EV30, EV-D68, EV71, coxsackie B strains, and polio 1.
The disclosure also includes characterization and drug-like property assessment of example compounds, including 1H NMR, LCMS, and HPLC purity. Safety and disposition-related properties are supported by CYP3A4 inhibition IC50 values and by in vivo rat pharmacokinetics and related ADME parameters, including protein binding and microsomal metabolic stability.
Claims Coverage
The independent claim coverage centers on compounds of formula (I) with one of X and Y as C and the other as N, R1 limited to fluoro or methyl, and R2 limited to 3,4-dimethoxyphenyl or 1,3-dimethyl-1H-indazol-5-yl. The claim set includes pharmaceutically acceptable salts and dependent refinements that fix the X/Y assignment and select specific R1 and R2 values.
Compound of formula (I) with C/N ring-atom assignment
A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein one of X and Y is C and the other one is N.
Fluoro or methyl at R1
R1 is selected from fluoro and methyl.
Defined aromatic or heteroaryl R2 substituents
R2 is 3,4-dimethoxyphenyl or 1,3-dimethyl-1H-indazol-5-yl.
Compounds as pharmaceutically acceptable salts
A compound of formula (I) or a pharmaceutically acceptable salt thereof.
Fixed X=N and Y=C
In the compound, X is N, and Y is C.
R1 is fluoro
R1 is fluoro.
R2 is 3,4-dimethoxyphenyl
R2 is 3,4-dimethoxyphenyl.
Coverage is directed to pyrazolo[1,5-a]pyrimidin-7-amine compounds of formula (I) defined by the C/N assignment of X and Y, the R1 limitation to fluoro or methyl, and the R2 limitation to 3,4-dimethoxyphenyl or 1,3-dimethyl-1H-indazol-5-yl, including pharmaceutically acceptable salts. Dependent features further narrow the scope by fixing X and Y and selecting specific substituent values.
Stated Advantages
High antiviral activity combined with low or essentially negligible CYP3A4 inhibiting activity.
Reduced drug-drug interaction risk.
Documented Applications
Treatment of a picornaviral infection in a mammal by administering an effective amount of the compound or a pharmaceutically acceptable salt thereof.
Use in disorders linked to impaired, abnormal, or impaired autophagy via autophagy-modulating use.
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