Substituted pyridine and pyrazine compounds as PDE4 inhibitors

摘要

The invention provides a chemical entity of Formula (I);
wherein

R1, R2, R3, R4, Y and Z 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, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating peripheral disorders, including inflammatory and renal disorders.

主权项

1. A chemical entity of Formula (I): wherein: Z is N (nitrogen); R1 is —H; Y is —CH2—; R2 is a member selected from the group consisting of:
A) phenyl substituted with one or two Rd members, where each Rd is independently selected from the group consisting of: —CN, —CONH2, and —CO2C1-3alkyl;B) six-membered monocyclic heteroaromatic ring containing one or two nitrogen members unsubstituted or substituted with a member selected from the group consisting of: —CN, —OC1-3alkyl, —CONH2, —N(Rb)2, and —NH-cyclopropyl;C) five-membered monocyclic heteroaromatic ring containing two or three nitrogen members unsubstituted or substituted with one or two members each independently selected from the group consisting of —C1-3alkyl, —C1-3haloalkyl, —CH2ORb, —N(Rb)2, —NO2, —CO2CH3, and cyclopropyl; andD) oxazole optionally substituted with one or two Rb members; R3 is phenyl substituted with —Cl, —OC1-3alkyl, or —OC1-3haloalkyl; R4 is —C1-3alkyl; each Rb is independently —H or —CH3; wherein the chemical entity is selected from the group consisting of compounds of Formula (I), and pharmaceutically acceptable salts of compounds of Formula (I).