Tetrahydronaphthyridine and tetrahydropyrido[4,3-d]pyrimidine compounds and compositions thereof useful in the treatment of conditions associated with neurological and inflammatory disorders and dysfunctions

Inventors

Kelly, Michael G. • Kincaid, John • Kaub, Carl J.

Assignees

Evotec SE

Abstract

Fused heterocyclic compounds are disclosed that have formula 1: where A, B, L, N, R1, R3, R4′, Y and Z are as defined herein. The compounds and pharmaceutical compositions thereof are useful for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, cognitive disorders, anxiety, depression, and others.

Core Innovation

The patent discloses a family of compounds defined by formula 1 with variable substituents A and B, Y, W, Z, L, R1, R2, R2', R3, and R4 or —Z'-L'-R4. The scaffold includes A and B independently selected as CR2'R2', CO, or CS; Y as CR2'R2'; W as N; Z as O or NR2; and L as substituted or unsubstituted C1-C9 alkylene or substituted or unsubstituted C1-C9 heteroalkylene, with a separate variant in which L is a single bond.

The compounds further define R1 as a substituted or unsubstituted carbocyclic group or a substituted or unsubstituted heterocyclic group, R2 as hydrogen, C1-C6 alkyl, or C3-C8 cycloalkyl, each R2' as hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, aryl, or aralkyl, and R3 as substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, with a variant in which R3 is a carbocyclic group or a heterocyclic group. R4 is selected from a broad enumerated set including H, alkyl, —C(O)R20, —NR21C(O)R22, alkylamino, alkylthio, alkoxy, alkoxycarbonyl, alkylarylamino, arylalkyloxy, amino, aryl, arylalkyl, —SO2R23, substituted sulfanyl, aminosulfonyl, arylsulfonyl, dihydroxyphosphoryl, azido, carbamoyl, carboxyl, cyano, cycloalkyl, cycloheteroalkyl, dialkylamino, halo, heteroaryloxy, heteroaryl, heteroalkyl, hydroxy, nitro, and —SH.

The examples describe tetrahydro-pyrido[4,3-d]pyrimidin-amine scaffold members and related amino-substituted derivatives, including benzylamine, substituted benzylamine, and chiral ethylamine substituents. The examples include compounds with methoxy, chloro, fluoro, difluoro, trifluoromethyl, trifluoromethoxy, methanesulfonyl, phenoxy, and pyridinylmethyl or quinolinylmethyl patterns, and they are presented as specific structures and compound identifiers.

Claims Coverage

The claim coverage consists of two independent compound claims. Together, they define formula 1 compounds with detailed variable positions and substituent classes, and they also cover pharmaceutically acceptable salts, stereoisomers, tautomers, and isotopic variants.

Across the independent claims, the coverage centers on formula 1 compounds with variable atom and substituent positions, a defined R4 attachment group, and two linkage variants for L. Both claims expressly include pharmaceutically acceptable salts and stereochemical, tautomeric, and isotopic variants.

Stated Advantages

Documented Applications