3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanones as inhibitors of 11 (β)-HSD1

摘要

The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3,3-disubstituted-(8-aza-bicyclo[3.2.1]oct-8-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, 3,3-disubstituted-(6-aza-bicyclo[3.1.1]hept-6-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone, and 4,4-disubstituted piperidin-1-yl)-[5-(1H-pyrazol-4-yl)-thiophen-3-yl]-methanone compounds of the following formula that, inter alia, inhibit 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit 11β-hydroxysteroid dehydrogenase type 1; to treat disorders that are ameliorated by the inhibition of 11β-hydroxysteroid dehydrogenase type 1; to treat the metabolic syndrome, which includes disorders such as type 2 diabetes and obesity, and associated disorders including insulin resistance, hypertension, lipid disorders and cardiovascular disorders such as ischaemic (coronary) heart disease; to treat CNS disorders such as mild cognitive impairment and early dementia, including Alzheimer's disease; etc.

主权项

1. A compound of the following formula, or a pharmaceutically acceptable salt thereof: wherein:
-J1 and -J3 taken together form —CH2CH2—; -Q is pyrimidin-2-yl and has n substituents —RF;
n is independently 0 or 1;each —RF is independently —RZ, —F, —Cl, —CF3, —OH, —ORZ, —OCF3, —NH2, —NHRZZ, or —NRZZ2; each —RZ is independently unsubstituted saturated aliphatic C1-4alkyl; each —RZZ is independently saturated aliphatic C1-4alkyl; —Y is independently —OH or —CN; —RA1 is independently —H or —RAA; —RA2 is independently —H or —RAA; each —RAA is —RAA1; each —RAA1 is independently unsubstituted saturated aliphatic C1-4alkyl; —RB1 is independently —H or —RBB; —RB2 is independently —H or —RBB; each RBB is —RBB1; each —RBB1 is independently unsubstituted saturated aliphatic C1-4alkyl; —RN is independently —H or —RNN; and each —RNN is independently saturated aliphatic C1-4alkyl.