Substituted 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole and 4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine compounds as GlyT1 inhibitors
Inventors
Basinger, Jillian • Bookser, Brett • Chen, Mi • Chung, DeMichael • Gupta, Varsha • Hudson, Andrew • Kaplan, Alan • Na, James • Renick, Joel • Santora, Vincent
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9708334-B2
Publication Date
2017-07-18
Expiration Date
Abstract
The invention provides a chemical entity of Formula (I), wherein R1, R2, R3, R4, R5 and X have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive treatments; modulating and treating disorders mediated by GlyT1 activity; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma-dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training, including animal skill training; and treating other disorders, including pain and alcohol-dependence.
Core Innovation
The patent discloses a class of small-molecule compounds defined by Formula I (I), or pharmaceutically acceptable salts thereof, with substituent groups R1, R2, R3, R4, R5, and X constrained to enumerated structures and fragment patterns. The compounds are based on pyrrolo[3,4-c]pyrazole and pyrazolo[4,3-c]pyridine cores in selected compounds recited in the independent claim sets, and the chemical space includes halogenated aryl, heteroaryl, carbonyl, sulfonyl, cyano, and ether/alkoxy substituents.
The disclosure further presents specifically named selected compounds, including pyrrolo[3,4-c]pyrazole derivatives and pyrazolo[4,3-c]pyridine derivatives with substituted benzonitrile, benzamide, benzoyl, and methanone motifs. The listed structures include fluorophenyl, difluorophenyl, fluoropyridyl, methylpyridinyl, trifluoropropan-2-yloxy, trifluoroethoxy, isopropoxy, methanesulfonyl, and ethanesulfonyl substituents, together with pharmaceutically acceptable salts thereof.
The document also provides example-based characterization for multiple specific compounds, including 1H NMR data in CDCl3 or DMSO-d6 and [M+H]+ mass values. Additional examples are stated to be prepared analogously to earlier described examples, and the partial content includes compound identity coverage for representative numbered examples and related analogs.
Claims Coverage
The provided claim coverage centers on three independent claim groupings: one broad Formula I compound definition and two independent selections of specifically listed compounds. Across these claims, the inventive features are structural and comprise a constrained heterocyclic core with enumerated substituent choices, together with explicit selected compound lists and pharmaceutically acceptable salts.
Formula I compound definition with enumerated substituents
A compound of Formula I (I), or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, and X are each selected according to the enumerated fragment patterns and substituent options explicitly defined in the claim.
Selected pyrrolo[3,4-c]pyrazole compounds
A compound selected from the group consisting of the specifically listed pyrrolo[3,4-c]pyrazole-containing small molecules, including substituted aryl, benzonitrile, benzamide, benzoyl, methanone, sulfonyl, and ether-containing motifs, together with pharmaceutically acceptable salts thereof.
Selected pyrazolo[4,3-c]pyridine compounds
A compound selected from the group consisting of the specifically listed pyrazolo[4,3-c]pyridine-containing small molecules, including tetrahydro and related fused-ring structures with substituted benzonitrile, benzamide, benzoyl, sulfonyl, and ether-containing motifs, together with pharmaceutically acceptable salts thereof.
Overall, claim coverage is directed to a Formula I chemical framework with tightly enumerated substituent options, plus two independent selected compound sets covering pyrrolo[3,4-c]pyrazole and pyrazolo[4,3-c]pyridine derivatives. The claims also extend to pharmaceutically acceptable salts, and the provided dependent language adds pharmaceutical composition scope with a pharmaceutically acceptable excipient and an effective amount.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
Interested in licensing this patent?