Patent CA-2163158-A1 (CA)
Title: Methods for inhibiting bone loss
Inventor: GRESE TIMOTHY ALAN
IPC: A61K31/165
Filed: 1995-11-17
Abstract: The present invention provides methods for inhibiting bone loss comprising administering to a mammal in need of treatment a bone loss inhibiting amount of a compound of formula I or formula II       I wherein R1 is -H or is a bivalent moiety which distances L from the B-ring by 6-8 intervening atoms;   R2 is -H or selected from the group consisting of hydrogen, a straight or branched, saturated or unsaturated chain having 1-5 carbon atoms, a substituted or unsubstituted cycloalkyl group having 5-7 carbon atoms, a bivalent moiety which joins R3 and L to form a 5- to 7-membered heterocyclic ring, and halo-substituted derivatives of the foregoing;          R3 is absent or selected from the group consisting of hydrogen, a straight or branched, saturated or unsaturated chain having 1-5 carbon atoms, a substituted or unsubstituted bivalent moiety which joins R2 and L to form a 5- to 7-membered heterocyclic ring, and halo-substituted derivatives of the foregoing;          R4 is hydrogen or lower alkyl; R5 and R6 each are independently hydrogen, hydroxy, or a moiety which is converted to hydroxy in vivo;          L is -CON< or -N<; and the dotted line in the B-ring is an optional bond; or a pharmaceutically acceptable salt thereof; and   II wherein Q is a moiety having the formula   ; or ? R1 ? B ? R7 ? L ? G ;           R1 is absent or is a bivalent moiety which distances L from the B-ring by 6-8 intervening atoms;          R2 is absent or selected from the group consisting of hydrogen, a straight or branched, saturated or unsaturated chain having 1-5 carbon atoms, a substituted or unsubstituted cycloalkyl group having 5-7 carbon atoms, a bivalent moiety which joins R3 and L to form a 5- to 7-membered heterocyclic ring, and halo-substituted derivatives of the foregoing;          R3 is absent or selected from the group consisting of hydrogen, a straight or branched, saturated or unsaturated chain having 1-5 carbon atoms, a substituted or unsubstituted bivalent moiety which joins R2 and L to form a 5- to 7-membered heterocyclic ring, and halo-substituted derivatives of the foregoing;         L is -CON< or -N<; B is -O-, -S-, -CH2-phenyl-O-, -phenyl-O-, or -benzyl -O -;           R7 is absent or selected from the group consisting of straight- or branched-chain alkylene, straight- or branched-chain alkenylene, phenylene, and fluoro-substituted analogs of the foregoing;     G is a moiety which together with L forms a substituted or unsubstituted heterocyclic ring having at least one nitrogen atom or is selected from the group consisting of hydrogen, lower alkyl, lower alkenyl, lower alkynyl,  (C3-C7)cycloalkyl, halo(lower)alkyl, cyano(lower)alkyl, carboxy(lower)alkyl, (lower)alkoxycarbonyl(lower)alkyl,  (C6-C10)aryl,  (C7-C11)aryl akyl, di(lower)alkylamino(lower)alkyl, and fluoro-substituted analogs of the foregoing;          R4 is hydrogen or lower alkyl; R5 and R6 each are independently hydrogen, hydroxy, or a moiety which is converted to hydroxy in vivo;   Z is -O-, -S-, -CH2-, -NH-; or -N(CH3)-; and the dotted line in the B-ring is an optional bond; or a pharmaceutically acceptable salt thereof.