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
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11807626-B2
Publication Date
2023-11-07
Expiration Date
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 concerns a compound having Formula I, or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, or a deuterated analog thereof. The compound is defined by a pyridazinone moiety with structural constraints on ring A, group E, linkage group L, and substituent group G. The disclosure includes selected structural components and extensive substituent variables with compatibility and attachment rules.
Ring A is selected as a 5-6 membered aromatic ring or a 4-7 membered nitrogen containing heterocycloalkyl, with substitution limits and an attachment rule stating that when ring A is a nitrogen containing heterocycloalkyl, the pyridazinone moiety is attached to a nitrogen atom of A. Group E is phenyl or a 5 or 6 membered heteroaryl with substitution limits, and when E is a 5 or 6 membered heteroaryl, O is not attached to a heteroatom of E. Linkage group L is absent, or one of specified linkage moieties.
Group G is selected from cycloalkyl, cycloalkenyl, bridged carbocylic rings, carbocyclic spiro rings, heterocyclic spiro rings, phenyl, heterocycloalkyl, heterocycloalkenyl, bridged heterocylic rings, or heteroaryl, each with defined substitution options. The disclosure also includes specific examples of substituted 4-chloro-5-substituted pyridazin-3(2H)-ones and related (R)-configured structures with heteroaryl substituents, together with compound representations in embedded images and structure files.
Claims Coverage
The consolidated content includes two independent claim groups: one independent compound claim directed to Formula I with defined structural variables, and one independent claim directed to a selected group of specific compounds. Across these claims, the main coverage is the Formula I scaffold with constrained ring selections, linkage options, and substituent-group definitions, plus selected specific structures shown in the document.
Formula I compound with constrained ring and substituent frameworks
A compound having Formula I, or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein A is a 5-6 membered aromatic ring or a 4-7 membered nitrogen containing heterocycloalkyl with substitution constraints and attachment rules, E is phenyl or a 5 or 6 membered heteroaryl with substitution constraints and an O-linkage restriction, L is absent or one of specified linkage moieties, and G is one of multiple enumerated cyclo/carbocyclic/heterocyclic/phenyl frameworks with defined substituent options.
Selected specific compound structures
A compound selected from the group consisting of specific compounds, or a pharmaceutically acceptable salt thereof.
Claim coverage is centered on Formula I compounds defined through constrained selections for A, E, L, and G, with substitution-variable and attachment rules. A second independent claim covers a selected group of specific compounds, including pharmaceutically acceptable salts.
Stated Advantages
CD73 inhibition as measured in enzymatic luciferase/CellTiter-Glo® and CHO-K1 stable human CD73 cell-based assays, with IC50 values reported.
Documented Applications
Methods of treating CD73-mediated diseases or conditions by administering an effective amount of a compound of Formula I to a subject.
Pharmaceutical compositions comprising the compound of Formula I together with a pharmaceutically acceptable carrier.
Use of the disclosed compound embodiments in CD73 inhibition testing, including luciferase/CellTiter-Glo® indirect assay measuring AMP conversion to adenosine and a CHO-K1 cell-based CD73 inhibition assay using stable human CD73 expression [procedural detail omitted for safety].
Interested in licensing this patent?