Cycloalkyl-hydroxyl compounds and compositions for cholesterol management and related uses

摘要

The present invention relates to novel cycloalkyl-hydroxyl compounds, compositions comprising hydroxyl compounds, and methods useful for treating and preventing a variety of diseases and conditions such as, but not limited to aging, Alzheimer's Disease, cancer, cardiovascular disease, diabetic nephropathy, diabetic retinopathy, a disorder of glucose metabolism, dyslipidemia, dyslipoproteinemia, hypertension, impotence, inflammation, insulin resistance, lipid elimination in bile, obesity, oxysterol elimination in bile, pancreatitis, Parkinson's disease, a peroxisome proliferator activated receptor-associated disorder, phospholipid elimination in bile, renal disease, septicemia, Syndrome X, thrombotic disorder. Compounds and methods of the invention can also be used to modulate C reactive protein or enhance bile production in a patient. In certain embodiments, the compounds, compositions, and methods of the invention are useful in combination therapy with other therapeutics, such as hypocholesterolemic and hypoglycemic agents.

主权项

1. A compound of formula I:or a pharmaceutically acceptable salt thereof, wherein:
(a) each occurrence of m is independently an integer ranging from 0 to 5; (b) each occurrence of n is independently an integer ranging from 3 to 7; (c) X is (CH2)z or Ph, wherein z is an integer from 0 to 4; (d) each occurrence of R1 and R2 is independently (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, phenyl, benzyl, or R1 and R2 and the carbon to which they are both attached are taken together to form a (C3-C7)cycloakyl group; (e) each occurrence of R11 and R12 and the carbon to which they are both attached are taken together to form a (C3-C7)cycloakyl group; (f) each occurrence of Y1 and Y2 is independently (C1-C6)aikyl, OH, COOH, COORS, SO3H, wherein:
(i) R3 is (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, phenyl, or benzyl and is unsubstituted or substituted with one or more halo, OH, (C1-C6)alkoxy, or phenyl groups,(ii) each occurrence of R4 is independently H, (C1-C6)alkyl, (C2-C6)alkenyl, or (C2-C6)alkynyl and is unsubstituted or substituted with one or two halo, OH, C1-C6 alkoxy, or phenyl groups; and(iii) each occurrence of R5 is independently H, (C1-C6)alkyl, (C2-C6)alkenyl, or (C2-C6)alkynyl.