Methods for inhibiting bone loss

A - Human Necessities – 61 – K

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Details

A61K 31/55 (2006.01) A61K 31/35 (2006.01) A61K 31/352 (2006.01) A61K 31/353 (2006.01) A61K 31/38 (2006.01) A61K 31/382 (2006.01) A61K 31/445 (2006.01) A61K 31/4453 (2006.01) A61K 31/453 (2006.01) A61K 31/4725 (2006.01) A61K 31/565 (2006.01)

Patent

CA 2163158

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 Image 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 Image II wherein Q is a moiety having the formula Image ; 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.

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