Compounds and methods for CD73 modulation and indications therefor

Inventors

Shi, Songyuan • BUELL, JOHN • Guo, Zuojun • Ly, Cuong • Spevak, Wayne • Vander Wal, Mark • Walleshauser, Jack • Zhang, Chao • Zhang, Jiazhong

Assignees

Opna Bio SA

Abstract

Disclosed are compounds of Formula I:or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein R1, R2, R3, A, E, L, and G are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.

Core Innovation

The invention provides compounds, or pharmaceutically acceptable salts thereof, defined by a detailed multi-parameter structural formula with constrained substituent patterns and attachment rules. The core scaffold includes a pyridazinone-containing framework with a heteroaryl group G substituted with 0-3 T5 and 0-1 T3, and R2 is Cl, Br, CF3, or CN. The structure further defines T3, T5, R8, R9, T1, and Z1-Z5 with explicit allowed values and substitution limits.

T3 is limited to groups including (CH2)0-3-C(O)N(R8)R9, (CH2)0-3-N(R8)R9, (CH2)0-3-C(O)OR9, (CH2)0-3-cycloalkyl, (CH2)0-3-cycloalkenyl, (CH2)0-3-heterocycloalkyl, (CH2)0-3-heterocycloalkenyl, O-heterocycloalkyl optionally substituted with 4-chloropyridazin-3-one-5-yl, or (CH2)0-3-bridged carbocyclic ring. T5 is independently selected from halogen, hydroxyl, alkyl, alkenyl, alkynyl, CN, cyanoalkyl, alkoxyl, or alkoxyalkyl, subject to stated restrictions when attached to a heteroatom of G, and the claim also constrains how T3 and G may be attached.

The provided examples describe specific (R)-configured pyridazin-3(2H)-one compounds with chloropyridazinone cores, ether-linked cyclic amines, substituted pyridinyl and pyrazolyl/isoxazolyl motifs, and additional fluorinated or fused-ring variants. The examples also include diverse pendant groups such as pyrrolidine, piperidinyl, spiro, cycloalkyl, cycloalkenyl, and sulfonamide or nitrile-containing substituents, while the claim set frames the overall family as a structurally defined compound class with broader method-of-use context.

Claims Coverage

The consolidated claim coverage centers on one independent compound claim, with additional dependent claims refining the structure and extending to treatment methods. The independent claim defines a multi-parameter compound class with detailed substituent constraints across R2, G, T3, T5, R8, R9, T1, and Z1-Z5, and includes pharmaceutically acceptable salts.

The claim coverage is centered on a tightly defined compound class with explicit constraints on heteroaryl substitution, linker groups, and substituent sets, together with pharmaceutically acceptable salts. The claim set also extends to CD73-mediated disease or condition treatment by administering the claimed compound or a pharmaceutical composition.

Stated Advantages

Documented Applications