Selective CYP11B1 inhibitors for the treatment of cortisol dependent diseases

摘要

The present invention relates to compounds which selectively inhibit CYP11B1. Preferably, the compounds of the present invention do not substantially inhibit CYP11B2. Moreover, the compounds of the present invention do not substantially inhibit CYP17 and/or CYP19, either. Amongst other applications of the compounds of the present invention, they can be used for the treatment of Cushing's syndrome or metabolic disease.

主权项

1. A compound that selectively inhibits CYP11B1, wherein the compound
is a compound comprising pyridine and het groups of formula (2): wherein the pyridine group is bonded to a carbon in Het and wherein, Het is imidazolyl, pyridyl, isoxazolyl, or isothiazolyl, wherein Het is substituted with, C6-C13 aryl, and wherein C6-C13 aryl can optionally be substituted with R3, wherein where multiple substitution with R3 is possible, the substituents can be independently selected from R3, R3 is C1-C12 alkyl, haloalkyl, C1-C5 alkoxy, hydroxy, C6-C13 aryl, halogen, amino, amido, ester, ether, C(O)R4, OC(O)R4, SO2R4, SO2NHR4, CN, NO2 or OAc, R4 is H, OH, C1-C5 alkoxy, alkyl or aryl, R5 is H, R6 is H, C1-C12 alkyl, haloalkyl, cycloalkyl, C1-C5 alkoxy, hydroxy, halogen, alkenyl, cycloalkylene, alkynyl, naphthyl, furanyl, thiophen, benzo[b]thiophen, CN, NO2, OAc, amino, amido, C(O)R4, OC(O)R4, trityl; which may be unsubstituted or substituted further with R3, wherein where multiple substitution with R3 occurs, the substituents are independently selected from R3, R7 is H or a pharmaceutically acceptable derivative.