Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12264149-B2
Publication Date
2025-04-01
Expiration Date
Abstract
Disclosed herein are compounds and methods of treating diseases and/or conditions associated with FGFR inhibition.
Core Innovation
The invention relates to compounds of formula (I), or pharmaceutically acceptable salts thereof, defined by extensive structural variables including n and m, substituents R1 through R8, heteroaryl or aryl group Y, and ring-atom assignments Q5 through Q9. The scaffold allows spirocycloalkyl, spiroheterocycloalkyl, cycloalkyl, and bridged bicyclic ring formation, together with defined heteroatom and unsaturation patterns such as A = N or CH, Z = S(O)2 or S(O), and X = O, S, or NR.
The disclosure includes substituent definitions for optionally substituted groups and functional-group classes such as halogen, cyano, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, alkylthio, alkylamino, carbonyl, sulfonyl, and phosphonate-like moieties. The examples are described as substituted indazole-based heteroaromatic compounds and related heteroaromatic compounds with ethoxy-linked pyridyl, pyrimidyl, pyridazinyl, nicotinonitrile, piperazine, piperidine, azetidine, morpholine, diazaspiro, oxaazaspiro, and sulfonamide-containing motifs.
The examples are presented as specific structure-defined embodiments, including stereochemical variants such as (R), (S), (1R), and (1S), and named compounds with fluoro, chloro, methyl, methoxy, difluoro, trifluoromethyl, sulfone, sulfonamide, carboxamide, carboxylate, and carbonitrile substituents. Analytical characterization by LCMS and 1H NMR is reported for the examples, and the record also lists specific compound names corresponding to the described scaffold families.
Claims Coverage
The consolidated claim coverage centers on broad independent compound claims to formula (I) or pharmaceutically acceptable salts thereof, together with dependent and parallel claim material that narrows the scaffold and extends to composition and treatment claims. The recurring inventive features are the formula (I) scaffold, the ring-formation rules, the defined heteroatom and atom-pattern constraints, and the therapeutic use claims.
Compound of formula (i) scaffold
A compound of formula (I), or a pharmaceutically acceptable salt thereof, defined by n = 1, 2, or 3; m = 0, 1, 2, or 3; and variable definitions for R1, R2, R3, R4, R4', R5, R6, R7, R8, A, Z, X, Y, and Q5-Q9.
Spiro, cyclo, and bridged ring formation
R1 and R2 groups can form optionally substituted spirocycloalkyl or spiroheterocycloalkyl rings, cycloalkyl rings, and bridged bicyclic ring systems.
Defined heteroatom and atom-pattern constraints
A is N or CH; Z is S(O)2, S(O), O, NR3, or CR4R4'; X is O, S, or NR; Y is an optionally substituted 5- or 6-membered heteroaryl ring or an optionally substituted 6-membered aryl ring; and Q5, Q6, Q7, Q8, and Q9 are each independently N or CR5 with one or two positions being N.
Specific formula variants and substituent selections
Dependent claims refine the scaffold with specific formula variants such as IA-8, enumerated R9 substituent options, and fixed Q5-Q9 atom assignment patterns, including halogen and hydrogen selections.
Pharmaceutical composition and cancer treatment
Dependent claims cover a pharmaceutical composition comprising the compound and a pharmaceutically acceptable excipient, and a method of treating cancer by administering the compound or a pharmaceutically acceptable salt thereof.
Overall, the claims define a broad formula-based indazole scaffold with detailed ring, heteroatom, and substituent control, then narrow the scope through specific variants, atom-pattern selections, composition claims, and cancer-treatment claims.
Stated Advantages
FGFR4 inhibitor candidates provide isoform selectivity toward FGFR4 over FGFR1, FGFR2, and FGFR3, and broader kinase selectivity toward FGFR kinase over non-FGFR kinases.
The compounds are described as having CNS penetration, including blood-brain barrier crossing and CNS penetrance.
The compounds are described as having favorable pharmacokinetic/pharmacodynamic attributes, including high GI absorption, low clearance, and low drug-drug interaction potential.
Documented Applications
Therapeutic use for cancer, including specified cancer types and FGFR-mutant cancer.
Diagnostic and treatment decision frameworks for detecting FGFR dysregulation, including FGFR inhibitor resistance mutations, using FDA-approved assays, liquid biopsy concepts, circulating tumor DNA monitoring, pyrosequencing, immunohistochemistry, and break-apart FISH.
Treatment of cancer in a subject by administering the claimed compound or a pharmaceutically acceptable salt thereof, including urothelial carcinoma, breast carcinoma, endometrial adenocarcinoma, ovarian carcinoma, primary glioma, cholangiocarcinoma, gastric adenocarcinoma, non-small cell lung carcinoma, pancreatic exocrine carcinoma, oral, prostate, bladder, colorectal carcinoma, renal cell carcinoma, neuroendocrine carcinoma, myeloproliferative neoplasms, head and neck (squamous), melanoma, leiomyosarcoma, and sarcomas.
Interested in licensing this patent?