Azaquinazoline inhibitors of atypical protein kinase C
Inventors
Breslin, Henry J. • Dorsey, Bruce D. • Dugan, Benjamin J. • Hudkins, Robert L. • Mesaros, Eugen F. • Ott, Gregory R. • Zificsak, Craig A. • Zulli, Allison L. • Tao, Ming • Fowler, Katherine M. • Morris, Emma L. • Pave, Gregoire A. • Roffey, Jonathan R. A. • Monck, Nathaniel J. T. • Soudy, Christelle N. • Olowoye, Ikeoluwa
Assignees
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Publication Number
US-9896446-B2
Publication Date
2018-02-20
Expiration Date
Abstract
The present application provides a compound of formula (I) or a salt thereof, wherein R7, R8, R9, G, and X are as defined herein. This application further describes compositions comprising the same. Compounds of formula (I) and their salts have aPKC inhibitory activity, and may be used to treat proliferative diseases.
Core Innovation
The invention is directed to substituted heteroaromatic amine compounds, or pharmaceutically acceptable salts thereof, centered on pyrido[3,4-d]pyrimidine cores linked to substituted pyridinyl and amine moieties. The disclosed compounds include piperazine, piperidine, pyrrolidinyl, morpholine, and pyrazole substituents, together with cyclopropyl, cyclobutyl, fluoro, chloro, difluoro, trifluoromethyl, and trifluoro-ethyl variations. The compound set is presented as specific named members within a common heteroaromatic amine family.
The documents further describe analytical characterization and structural depictions for the listed compounds. Reported data include LCMS or MS ion values, retention times, and 1H NMR spectra or peak assignments in solvents such as DMSO, CDCl3, and d6-DMSO. Some entries also include stereochemical designations, supporting identification of the specific compound members that share the same pyrido[3,4-d]pyrimidine-based framework.
The disclosure further presents specific named compounds and selected compound groups as pharmaceutically acceptable salts. In the portions that describe biological scope, the document identifies azaquinazoline small-molecule aPKC inhibitors and states use for treating aPKC-dependent disorders and proliferative diseases.
Claims Coverage
The consolidated claim coverage centers on one independent claim that recites a compound selected from a defined group of substituted heteroaromatic amines, together with pharmaceutically acceptable salts. Across the combined input, the inventive features are the specific pyrido[3,4-d]pyrimidine-based scaffold, the defined terminal heteroaryl/aryl amine substituents, and dependent pharmaceutical composition claims including a pharmaceutically acceptable excipient.
Selected substituted heteroaromatic amine compound group
A compound selected from a listed group of specifically named substituted heteroaromatic amines, including pyrido[3,4-d]pyrimidine-based structures and related heteroaromatic amines, or a pharmaceutically acceptable salt thereof.
Piperazinyl and related amine substitution on a pyrido[3,4-d]pyrimidine scaffold
The selected compounds include pyrido[3,4-d]pyrimidine cores substituted with piperazin-1-yl, piperidine, piperazine-containing, and related amine substituents, with additional heteroaryl or aryl amine linkages.
Cyclopropyl and cyclobutyl substituted variants
The covered set includes cyclopropyl- and cyclobutyl-containing members, including compounds with 5-cyclopropyl or 5-cyclobutyl substitution on the heteroaromatic scaffold.
Fluorinated, chlorinated, and pyrazolyl variants
The listed members include fluorinated and chlorinated substituents, including fluoro, difluoro, trifluoro, trifluoromethyl, and chloro/ethyl pyrazolyl or trifluoroethyl pyrazolyl patterns.
Pharmaceutical composition with pharmaceutically acceptable excipient
A pharmaceutical composition comprising the selected compound and a pharmaceutically acceptable excipient.
Pharmaceutically acceptable salt forms
The selected compounds are also claimed as pharmaceutically acceptable salts thereof.
Overall, the claims cover a defined set of substituted heteroaromatic amines built around a pyrido[3,4-d]pyrimidine scaffold with specific heteroaryl, piperazinyl, piperidine, cyclopropyl, cyclobutyl, fluorinated, chlorinated, and pyrazolyl variations, together with pharmaceutically acceptable salt forms and pharmaceutical compositions containing an excipient.
Stated Advantages
Treating aPKC-dependent disorders.
Treating proliferative diseases.
Documented Applications
Use for treating aPKC-dependent disorders.
Use for treating proliferative diseases.
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