Substituted benzofuranyl and benzoxazolyl compounds and uses thereof
Inventors
Baloglu, Erkan • Shacham, Sharon • Senapedis, William • McCauley, Dilara • Landesman, Yosef • Golan, Gali • Kalid, Ori • Shechter, Sharon
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12331040-B2
Publication Date
2025-06-17
Expiration Date
Abstract
The invention generally relates to substituted benzofuranyl and substituted benzoxazolyl compounds, and more particularly to a compound represented by Structural Formula A: or a pharmaceutically acceptable salt thereof, wherein the variables are as defined and described herein. The invention also includes the synthesis and use of a compound of Structural Formula A, or a pharmaceutically acceptable salt or composition thereof, e.g., in the treatment of cancer (e.g., mantle cell lymphoma), and other diseases and disorders.
Core Innovation
The invention relates to compounds represented by Structural Formula V or VI, including pharmaceutically acceptable salts. The compounds are defined by substituent constraints in which R1a is selected from optionally substituted C6-C12 aryl or optionally substituted C5-C12 heteroaryl, R9a and R2 are each selected from optionally substituted aryl or optionally substituted heteroaryl, and m' is 1 or 2.
The disclosure includes benzofuran-containing acrylamide scaffolds, including (E)-acrylamide derivatives with 6-aminopyridin-3-yl or related aminopyridyl motifs and varied substituted benzofuran aryl/heteroaryl groups. The examples describe specific compounds and intermediates bearing chloro, fluoro, difluoro, trifluoromethyl, methoxy, morpholine-4-carbonyl, piperidine-1-carbonyl, pyrrolidine-1-carbonyl, azetidine-1-carbonyl, piperazine carbonyl, sulfonyl, and sulfonyl-type motifs, together with benzofuran-2-yl structural elements and heterocyclic variations.
Characterization is reported with 1H NMR and LCMS, together with yields, retention times, and m/z values for compounds and intermediates. The disclosure further describes synthetic relationships used to access the exemplified compounds, including Pd-catalyzed coupling, Boc deprotection, amide or acrylamide formation, and chiral resolution in some examples.
Claims Coverage
The consolidated claim coverage centers on one independent structural claim to compounds represented by Structural Formula V or VI, with constrained substituent selections for R1a, R9a, R2, and m' equal to 1 or 2, including pharmaceutically acceptable salts. The claim set further includes five inventive feature groupings by narrowing R2 and R9a, selecting from depicted chemical structures, adding therapeutic method language, and imposing a heterocycle substitution-count limitation.
Structural Formula V or VI compound scaffold
A compound represented by Structural Formula V or VI, where R1a is selected from optionally substituted C6-C12 aryl or optionally substituted C5-C12 heteroaryl, R9a is optionally substituted aryl or optionally substituted heteroaryl, R2 is optionally substituted aryl or optionally substituted heteroaryl, m' is 1 or 2, including pharmaceutically acceptable salts.
R2 selected from an enumerated heteroaryl set
R2 is selected from 6-aminopyridin-3-yl, pyridin-3-yl, pyridin-2-yl, 3,5-dimethylisoxazol-4-yl, and thiazol-4-yl.
R9a selected from a listed substituted aryl or heteroaryl group set
R9a is one of the listed substituted phenyl, pyridyl, pyrimidinyl, pyridazinyl, benzofuran-2-yl, and related groups described in the claim.
Selected from depicted chemical structures
The compound is selected from a set of depicted chemical structures, including compounds represented in attached chemical format files.
Therapeutic treatment by administration
A method of treating a subject with a disorder by administering a therapeutically effective amount of a compound of the scaffold or a pharmaceutically acceptable salt thereof, where the disorder is selected from cancer, a neurodegenerative disease, immune system disease, osteosarcoma, childhood rhabdomyosarcoma, or childhood Ewing's sarcoma.
Heterocycle substitution count constraint
A compound where the heterocycle formed by R11 and R12 together with the attached nitrogen is optionally substituted with 1, 2, 3 or 4 substituents independently selected from halo, hydroxyl, haloC1-C3 alkyl, (C1-C3) alkyl, and C1-C3 alkoxy.
Overall, the claims cover a Structural Formula V or VI compound family with constrained aryl/heteroaryl substituent selections at R1a, R2, and R9a, along with pharmaceutically acceptable salts. The scope is further narrowed by enumerated R2 and R9a options, selection from depicted structures, a therapeutic administration claim for specified disorders, and a substitution-count limitation on a defined heterocycle.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating a subject with cancer, a neurodegenerative disease, immune system disease, osteosarcoma, childhood rhabdomyosarcoma, or childhood Ewing's sarcoma by administering a therapeutically effective amount of a compound of the scaffold or a pharmaceutically acceptable salt thereof.
Treating a subject with a disorder by administering a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, where the disorder is cancer, a neurodegenerative disease, or an immune system disease.
Interested in licensing this patent?