Antiviral pyrazolopiridinone compounds
Inventors
KONST, Zef • Lu, Yipin • Moreau, Robert Joseph • Rajapaksa, Naomi Samadara • SHEARN-NANCE, Galen • TULLY, David Charles • Turner, Michael Robert • Young, Joseph Michael • Zhao, Qian • Corkey, Britton K. • Metobo, Samuel E.
Assignees
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Publication Number
US-12338220-B2
Publication Date
2025-06-24
Expiration Date
Abstract
The invention provides compounds of Formula (I) as described herein, along with pharmaceutically acceptable salts, pharmaceutical compositions containing such compounds, and methods to use these compounds, salts and compositions for treating viral infections, particularly infections caused by herpesviruses.
Core Innovation
The invention relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, defined by a structural framework that includes a heteroaryl, heterocycloalkyl, or heterocyclyl fragment X and a linkage pattern through Y, L, Z, and A. The formula specifies attachment points indicated by * and **, variable ring and linker parameters m, n, p, q, and t, and allows single or double bond representation within the defined structure.
The structural definition includes broad but constrained substituent patterns for RB, R1, R2, R3, R5, R6, R10, R11, R12, R13, R14, R15, R16, and R17. The inputs describe optional ring formation between R1 and R2, ring formation within R5 and R6 sets, optional substitution of R10, and fused-ring formation through R17, while preserving the same Formula (I) scaffold.
The provided examples and partial descriptions identify substituted pyrazolo[3,4-c]pyridine-3-carboxamide derivatives, including N-(4-cyanobenzyl) compounds, sulfonyl-cyclopropyl substituted intermediates, and related stereochemical variants. The documents also describe characterized intermediates and compounds, including hydrazone intermediates, brominated derivatives, azide/amine variants, and chiral forms reported with LCMS, MS, 1H NMR, TLC, RP-HPLC, or SFC data.
Claims Coverage
The consolidated claim coverage centers on one broad independent Formula (I) claim family and dependent refinements present in the inputs. The inventive features combine the Formula (I) scaffold, defined attachment/linkage architecture, extensive substituent options, pharmaceutically acceptable salt forms, and in some items pharmaceutical composition and herpesvirus treatment method coverage.
Formula (I) compound framework with defined attachment architecture
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, defined by X, Y, L, Z, A, q, m, n, p, and t, with attachment points indicated by * and ** and with single or double bond representation in the formula.
Variable heteroaryl or heterocycle fragment X
X is selected from a 5-6 membered heteroaryl having 1 to 4 heteroatoms independently selected from N, O and S, or a 5-6 membered heterocycloalkyl or heterocyclyl containing 1 to 4 ring members independently selected from N, NH, NR17, O or S.
Defined linkage and linker pattern for Y, L, and Z
Y is a bond, O, or —O— with attachment to X and RB as indicated; L is a C1-C4 straight chain or branched alkylene linker; Z connects to LMC and L by defined attachment points; and A is a bond.
Extensive substituent scope for RB and variable groups
RB is H, C1-C6 alkyl, phenyl, pyridinyl, thiophenyl, pyrimidinyl, or a 5-8 membered cycloalkyl optionally substituted with R5 groups; R1 and R2 are H, C1-C3 alkyl, or C1-C3 alkyl substituted with OH groups, with optional cycloalkyl ring formation; and R3, R5, R6, R10, R11, R12, R13, R14, R15, R16, and R17 each have defined selectable substituent sets and ring-forming options.
Pharmaceutically acceptable salt form
The Formula (I) compound is expressly provided as a pharmaceutically acceptable salt thereof.
Pharmaceutical composition with carrier
A pharmaceutical composition comprising the Formula (I) compound together with at least one pharmaceutically acceptable carrier.
Method of treating herpesvirus infection
A method of treating a herpesvirus infection by administering to a patient a Formula (I) compound or a pharmaceutical composition containing that compound.
Herpesvirus selection for treatment method
The herpesvirus is selected from CMV, EBV, VZV, HSV-1, HSV-2, herpesvirus 6, human herpesvirus 7, and Kaposi's sarcoma-associated herpesvirus.
The consolidated claim scope is a broad Formula (I) compound family defined by X/Y/L/Z architecture, parameterized ring and linker variables, and extensive substituent rules for multiple positions, with additional coverage for pharmaceutically acceptable salts, carrier-containing pharmaceutical compositions, and herpesvirus treatment methods in the items that provide those claims.
Stated Advantages
Inhibit herpesvirus DNA polymerases.
Not incorporated by human polymerases.
Activity against GCV-resistant virus.
Documented Applications
Treating or preventing herpesvirus diseases or infections in humans, including immunocompromised settings.
Treating congenital CMV.
Genital herpes.
Oral herpes (cold sores).
Herpetic keratitis.
Neonatal herpes.
Herpes encephalitis.
Herpes zoster (shingles).
Infectious mononucleosis.
PTLD.
Castelman's disease.
Hemophagocytic lymphohistiocytosis.
Alzheimer’s disease.
Chronic fatigue syndrome (CFS).
Systemic lupus erythematosus (SLE).
Multiple sclerosis (MS).
Rheumatoid arthritis (RA).
Juvenile idiopathic arthritis (JIA).
Inflammatory bowel disease (IBD).
Celiac disease.
Type 1 diabetes.
Atherosclerosis.
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