SUBSTITUTED PYRIDIN-4-ONES AND THEIR USE AS GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS.

摘要

GnRH receptor antagonists of formula (I) are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof, including stereosomers, prodrugs and pharmaceutically acceptable salts thereof, wherein: A is O or a bond; n is 1, 2, 3 or 4; R1 and R2 are the same or different and independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocycle, substituted heterocycle, heterocyclealkyl, susbstituted heterocyclealkyl, -C(R8)(=NR9) or -C(NR10R11)(=NR9); or R1 and R2 taken together with the nitrogen atom to which they are attached form a heterocycle or a substituted heterocycle; R3a and R3b are the same or different and, at each occurrence, independently hydrogen, alkyl, substituted alkyl, alkoxy, alkylthio, alkylamino, aryl, substituted aryl, arylakyl, substituted arylalkyl, heterocycle, substituted heterocycle, heterocyclealkyl, substituted heterocyclealkyl, -COOR12 or -CONR10R11; or R3ab and R3b taken together with the carbon atom to which they are attached form a homocycle, substituted homocycle, heterocycle or substituted heterocycle; or R3a and the carbon to which it is attached taken together with R1 and the nitrogen to which it is attached form a heterocycle or substituted heterocycle; R4 is hydrogen, alkyl or substituted alkyl; R5 is arylalkyl, substituted arylalkyl, heteroarylalkyl or substituted heteroalalkyl; R6 is aryl, substituted aryl, heteroaryl or substituted heteroaryl; R7 is hydrogen, alkyl or substituted alkyl; R8, R9, R10 and R11 are the same or different and, at each occurrence, independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heterocycle, substituted heterocycle, heterocyclealkyl or substituted heterocyclealkyl, and R12 is hydrogen, alkyl or substituted alkyl.