Substituted cyclopenta[c]pyrroles as ABHD6 antagonists

Inventors

Yoshida, Atsushi • HYAKUTAKE, Ryuichi • Nagashima, Nozomu • MISU, Ryosuke • Mori, Shohei

Assignees

Ono Pharmaceutical Co Ltd

Abstract

A drug is provided, which containing, as an active ingredient, a compound having ABHD6 inhibitory activity in prevention and/or treatment of a disease associated with ABHD6. A compound of formula (I-A) or a pharmaceutically acceptable salt thereof has ABHD6 inhibitory activity and therefore is useful as a pharmaceutical ingredient having potent ABHD6 inhibitory activity in the prevention and/or treatment of a disease associated with ABHD6: in which all symbols represent the same meaning as the symbols described in the specification.

Core Innovation

The patent discloses ABHD6-targeting small molecules, including substituted cyclopenta[c]pyrrole compounds, stereodefined bicyclic lactam/amidine-type core compounds, and compounds defined by a chemical formula, or pharmaceutically acceptable salts thereof. The disclosure includes pyridazinyl amino substituents attached to a hexahydrocyclopenta[c]pyrrol-2(1H)-yl or related bicyclic framework, together with varied acyl/aryl-thienyl substituents and defined stereochemistry.

The compounds include formula-defined embodiments with substituent variables and preferred embodiments, as well as stereochemically defined substituted methanone structures and related reference intermediates. The disclosure includes pharmaceutical forms such as pharmaceutically acceptable salts and pharmaceutical compositions comprising a pharmaceutically acceptable carrier and the compound as an active ingredient.

The patent describes ABHD6 inhibitory activity, ABHD6 binding affinity determined by BRET, and ABHD6 selectivity versus MAGL and FAAH using ABPP in rat brain membranes. It further states use for prevention and/or treatment of diseases associated with ABHD6, including pain, neurological diseases, inflammatory diseases, autoimmune diseases, metabolic diseases, and malignant tumors, and reports an in vivo analgesic effect in a rat MIA model.

Claims Coverage

The independent claims cover formula-defined compounds, including pharmaceutically acceptable salts, and pharmaceutical compositions comprising a pharmaceutically acceptable carrier and the claimed compound as an active ingredient. Across the combined claim sets, the main inventive features are the formula-defined ABHD6-targeting compounds, stereochemically defined substituted methanone embodiments, and the corresponding pharmaceutical compositions.

Overall, the claim coverage centers on formula-defined ABHD6-targeting compounds, including stereochemically defined substituted methanone embodiments and pharmaceutically acceptable salts, together with pharmaceutical compositions that incorporate these compounds as active ingredients.

Stated Advantages

Documented Applications