Claims for Patent: 6,288,120

Summary for Patent: 6,288,120

Title:	Prevention of loss and restoration of bone mass by certain prostaglandin agonists
Abstract:	Prostaglandin agonists of formula (I), in which, for example, A is a sulphonyl or acyl group, B is N or CH, M contains a ring and K and Q are linking groups, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits useful for the treatment of bone disorders including osteoporosis. ##STR1##
Inventor(s):	Cameron; Kimberly O. (East Lyme, CT), Ke; Hua Z. (Ledyard, CT), Lefker; Bruce A. (Gales Ferry, CT), Rosati; Robert L. (Mystic, CT), Thompson; David D. (Gales Ferry, CT)
Assignee:	Pfizer Inc. (New York, NY)
Application Number:	09/331,081
Patent Claims:	1. A compound having the Formula I ##STR30## or a pharmaceutically acceptable salt or prodrug thereof wherein A is (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.7)cycloalkyl or (C.sub.3 -C.sub.7 cycloalkyl(C.sub.1 -C.sub.6)alkyl, said A moieties optionally mono-, di- or tri-substituted on carbon independently with hydroxy, (C.sub.1 -C.sub.4)alkyl or halo; Q is --(C.sub.2 -C.sub.6)alkylene-W-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.3 -C.sub.8)alkylene-, said -(C.sub.3 -C.sub.8)alkylene- being straight chain with the proviso that (C.sub.3 -C.sub.3)alkylene may be optionally substituted with up to four substituents independently selected from fluoro or (C.sub.1 -C.sub.4)alkyl, --X-(C.sub.1 -C.sub.5)alkylene-, --(C.sub.1 -C.sub.5)alkylene-X-, --(C.sub.1 -C.sub.3)alkylene-X-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.2 -C.sub.4)alkylene-W-X-(C.sub.0 -C.sub.3)alkylene-, --(C.sub.0 -C.sub.4)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.2 -C.sub.5)alkylene-W-X-W-(C.sub.1 -C.sub.3)alkylene-, wherein the two occurrences of W are independent of each other, --(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-, --(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-(C.sub.0 -C.sub.5)alkylene-, --(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-, or --(C.sub.1 -C.sub.4)alkylene-ethenylene-X-(C.sub.0 -C.sub.3)alkylene-; W is oxy, thio, sulfino, sulfonyl, aminosulfonyl-, -mono-N-(C.sub.1 -C.sub.4)alkyleneaminosulfonyl-, sulfonylamino, N-(C.sub.1 -C.sub.4)alkylenesulfonylamino, carboxamido, N-(C.sub.1 -C.sub.4)alkylenecarboxamido, carboxamidooxy, N-(C.sub.1 -C.sub.4)alkylenecarboxamidooxy, carbamoyl, -mono-N-(C.sub.1 -C.sub.4)alkylenecarbamoyl, carbamoyloxy, or -mono-N-(C.sub.1 -C.sub.4)alkylenecarbamoyloxy, wherein said W alkyl groups are optionally substituted on carbon with one to three fluorines; X is a five or six membered aromatic ring optionally having one or two heteroatoms selected independently from oxygen, nitrogen, and sulfur; said ring optionally mono-, or di-substituted independently with halo, (C.sub.1 -C.sub.3)alkyl, trifluoromethyl, trifluoromethyloxy, difluoromethyloxy, hydroxyl, (C.sub.1 -C.sub.4)alkoxy, or carbamoyl; Z is carboxyl, (C.sub.1 -C.sub.6)alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl, 5-oxo-1,2,4-oxadiazolyl, (C.sub.1 -C.sub.4)alkylsulfonylcarbamoyl or phenylsulfonylcarbarnoyl; K is a bond, (C.sub.1 -C.sub.8)alkylene, thio(C.sub.1 -C.sub.4)alkylene or oxy(C.sub.1 -C.sub.4)alkylene, said (C.sub.1 -C.sub.8)alkylene optionally mono-unsaturated and wherein K is optionally mono-, di- or tri-substituted independently with fluoro, methyl or chloro; M is --Ar, --Ar.sup.1 --V--Ar.sup.2, --Ar.sup.1 --S--Ar.sup.2 or --Ar.sup.1 --O--Ar.sup.2 wherein Ar, Ar.sup.1 and Ar.sup.2 are each independently a partially saturated, fully saturated or fully unsaturated five to eight membered ring or, a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated five or six membered rings, taken independently; said Ar, Ar.sup.1 and Ar.sup.2 moieties optionally substituted, on one ring if the moiety is monocyclic, or one or both rings if the moiety is bicyclic, on carbon with up to three substituents independently selected from R.sup.1, R.sup.2 and R.sup.3 wherein R.sup.1, R.sup.2 and R.sup.3 are hydroxy, nitro, halo, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.4)alkoxy(C.sub.1 -C.sub.4)alkyl, (C.sub.1-C.sub.4)alkoxycarbonyl, (C.sub.1 -C.sub.7)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkanoyl, formyl, (C.sub.1 -C.sub.8)alkanoyl, (C.sub.1 -C.sub.6)alkanoyl(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.4)alkanoylamino, (C.sub.1 -C.sub.4)alkoxycarbonylamino, sulfonamido, (C.sub.1 -C.sub.4)alkylsulfonamido, amino, mono-N- or di-N,N-(C.sub.1 -C.sub.4)alkylamino, carbamoyl, mono-N- or di-N,N-(C.sub.1 -C.sub.4)alkylcarbamoyl, cyano, thiol, (C.sub.1 -C.sub.6)alkylthio, (C.sub.1 -C.sub.6)alkylsulfinyl, (C.sub.1 -C.sub.4)alkylsulfonyl or mono-N- or di-N,N-(C.sub.1 -C.sub.4)alkylaminosulfinyl; R.sup.1, R.sup.2 and R.sup.3 are optionally mono-, di- or tri-substituted on carbon independently with halo or hydroxy; and V is a bond or (C.sub.1 -C.sub.3)alkylene optionally mono- or di-substituted independently with hydroxy or fluoro with the proviso that when K is (C.sub.2 -C.sub.4)alkylene and M is Ar and Ar is cyclopent-1-yl, cyclohex-1-yl, cyclohept-1-yl or cyclooct-1-yl then said (C.sub.5 -C.sub.8)cycloalkyl substituents are not substituted at the one position with hydroxy. 2. A compound as recited in claim 1 wherein said A moieties optionally mono-, di-, or tri-substituted on carbon with fluoro; X is phenyl, thienyl, or thiazolyl said phenyl, thienyl or thiazolyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethoxy; W is oxy, thio or sulfonyl; Z is carboxyl, (C.sub.1 -C.sub.4)alkoxycarbonyl or tetrazolyl; K is methylene or ethylene; Ar, Ar.sup.1 and Ar.sup.2 are each independently (C.sub.5 -C.sub.7)cycloalkyl or phenyl; R.sup.1 is halo, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.7)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, said (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.7)alkyl, (C.sub.3 -C.sub.7)cycloalkyl or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, optionally mono-, di- or tri-substituted independently with hydroxy, fluoro or chloro; and R.sup.2 and R.sup.3 are chloro, fluoro, methyl, methoxy, difluoromethoxy, trifluoromethoxy or trifluoromethyl. 3. A compound as recited in claim 2 wherein A is (C.sub.1 -C.sub.3)alkyl; Q is --(C.sub.2 -C.sub.6)alkylene-W-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.4 -C.sub.8)alkylene-, said -(C.sub.4 -C.sub.8)alkylene- straight chain optionally substituted with up to four substituents independently selected from fluoro or (C.sub.1 -C.sub.4)alkyl, --X-(C.sub.2 -C.sub.5)alkylene-, --(C.sub.1 -C.sub.5)alkylene-X-, --(C.sub.1 -C.sub.3)alkylene-X-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.2 -C.sub.4)alkylene-W-X-(C.sub.0 -C.sub.3)alkylene-, or --(C.sub.0 -C.sub.4)alkylene-X-W-(C.sub.1 --C.sub.3)alkylene-; M is --Ar.sup.1 --V--Ar.sup.2 or --Ar.sup.1 --O--Ar.sup.2 wherein Ar.sup.1 and Ar.sup.2 are each phenyl; V is a bond or (C.sub.1 -C.sub.2)alkylene; R.sup.1 is chloro, fluoro, (C.sub.1 -C.sub.4)alkyl or (C.sub.1 -C.sub.4)alkoxy, said (C.sub.1 -C.sub.4)alkyl and (C.sub.1 -C.sub.4)alkoxy optionally mono-, di- or tri-substituted independently with hydroxy or fluoro; and R.sup.2 and R.sup.3 are each independently chloro or fluoro. 4. A compound as recited in claim 3 wherein the compound is 7-[(2'-Hydroxymethyl-biphenyl-4-ylmethyl)-methanesulfonyl-amino]-heptanoic acid or 7-[(2'-Chloro-biphenyl-4-ylmethyl)-methanesulfonyl-amino]-heptanoic acid. 5. A compound as recited in claim 3 wherein A is methyl; Q is n-hexylene; Z is carboxyl; K is methylene; and M is 4-(2-hydroxymethylphenyl)phenyl. 6. A compound as recited in claim 3 wherein A is methyl; Q is n-hexylene; Z is carboxyl; K is methylene; and M is 4-(2-chlorophenyl)phenyl. 7. A compound as recited in claim 1 wherein A is (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.6)cycloalkyl or (C.sub.3 -C.sub.6)cycloalkyl(C.sub.1 -C.sub.6)alkyl; X is phenyl, thienyl, or thiazolyl said phenyl, thienyl or thiazolyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl, methoxy, difluoromethoxy or trifluoromethyloxy; W is oxy, thio or sulfonyl; Z is carboxyl, (C.sub.1 -C.sub.4)alkoxycarbonyl or tetrazolyl; K is (C.sub.1 -C.sub.8)alkylene or oxy(C.sub.1 -C.sub.4)alkylene, said (C.sub.1 -C.sub.8)alkylene optionally mono-unsaturated and wherein K is optionally mono-, di- or tri-substituted independently with methyl, fluoro or chloro; M is --Ar, said --Ar is phenyl, naphthalenyl, 1,2,3,4-tetrahydronaphthalenyl, cyclohexyl, cyclopentyl, cyclobutyl or cycloheptyl; R.sup.1 is halo, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.7)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.1 -C.sub.7)alkanoyl or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, said (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.7)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.1 -C.sub.7)alkanoyl or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, optionally mono-, di- or tri-substituted independently with hydroxy, fluoro or chloro; and R.sup.2 and R.sup.3 are each independently hydroxy, halo, trifluoromethyl, (C.sub.1 -C.sub.7)alkyl, (C.sub.1 -C.sub.4)alkoxy, (C.sub.1 -C.sub.5)alkanoyl, cyano, (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, formyl, difluoromethoxy, trifluoromethoxy or carbamoyl. 8. A compound as recited in claim 7 wherein A is (C.sub.1 -C.sub.3)alkyl; K is (C.sub.1 -C.sub.8)alkylene; --Ar is phenyl, cyclopentyl or cyclohexyl; and R.sup.1, R.sup.2 and R.sup.3 are each independently hydroxy, halo, trifluoromethyl, difluoroethoxy, trifluoromethoxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.7)alkyl. 9. A compound as recited in claim 7 wherein A is (C.sub.1 -C.sub.3)alkyl; K is oxy(C.sub.1 -C.sub.4)alkylene; --Ar is phenyl cyclopentyl or cyclohexyl; and R.sup.1, R.sup.2 and R.sup.3 are each independently hydroxy, halo, trifluoromethyl, difluoromethoxy, trifluoromethoxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.7)alkyl. 10. A compound as recited in claim 7 wherein K is methylene; A is (C.sub.1 -C.sub.3)alkyl; M is --Ar and --Ar is phenyl cyclopentyl or cyclohexyl wherein --Ar is substituted with at least R.sup.1 ; R.sup.1 is (C.sub.1 -C.sub.7)alkyl or (C.sub.1 -C.sub.5)alkoxy, said (C.sub.1 -C.sub.7)alkyl or (C.sub.1 -C.sub.5)alkoxy optionally mono-, di- or tri-substituted independently with hydroxy or fluoro; and R.sup.2 and R.sup.3 are each independently chloro, fluoro, methyl, difluoromethoxy, trifluoromethoxy or trifluoromethyl. 11. A compound as recited in claim 10 wherein the compound is 7-{[4-(1-Hydroxy-hexyl)-benzyl]-methanesulfonyl-amino]-heptanoic acid, 7-[(4-Butyl-benzyl)-methanesulfonyl-amino]-heptanoic acid or (3-{[(4-Butyl-benzyl)-methanesulfonyl-amino]-methyl}-phenyl)-acetic acid. 12. A compound as recited in claim 10 wherein Q is -(C.sub.2 -C.sub.6)alkylene-W-(C.sub.1 -C.sub.3)alkylene-; and W is oxy. 13. A compound as recited in claim 10 wherein Q is -(C.sub.3 -C.sub.8)alkylene-, said -(C.sub.3 -C.sub.8)alkylene- optionally substituted with from one to four fluorines. 14. A compound as recited in claim 13 wherein A is methyl; Q is n-hexylene; Z is carboxyl; K is methylene; and M is 4-(1-hydroxy-n-hex-1-yl)phenyl. 15. A compound as recited in claim 13 wherein A is methyl; Q is n-hexylene; Z is carboxyl; K is methylene; and M is 4-(n-but-1-yl)phenyl. 16. A compound as recited in claim 10 wherein Q is --X-(C.sub.1 -C.sub.5)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 17. A compound as recited in claim 10 wherein Q is -(C.sub.1 -C.sub.5)alkylene-X-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 18. A compound as recited in claim 10 wherein Q is -(C.sub.1 -C.sub.3)alkylene-X-(C.sub.1 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 19. A compound as recited in claim 18 wherein A is methyl; Q is 3-methylenephenylmethyl; Z is carboxyl; K is methylene; and M is 4-(n-but-1-yl)phenyl. 20. A compound as recited in claim 10 wherein Q is -(C.sub.2 -C.sub.4)alkylene-W-X-(C.sub.0 -C.sub.3)alkylene-; X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy; and W is oxy. 21. A compound as recited in claim 10 wherein Q is -(C.sub.0 -C.sub.4)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-; X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy; and W is oxy. 22. A compound as recited in claim 10 wherein Q is -(C.sub.2 -C.sub.4)alkylene-W-X-W-(C.sub.1 -C.sub.3)alkylene-; W is oxy; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 23. A compound as recited in claim 10 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-; and M is --Ar and --Ar is phenyl. 24. A compound as recited in claim 10 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-(C.sub.0 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 25. A compound as recited in claim 10 wherein Q is -(C.sub.1 -C.sub.3)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-; W is oxy; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 26. A compound as recited in claim 10 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-. 27. A compound as recited in claim 10 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-X-(C.sub.0 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 28. A compound as recited in claim 8 wherein the compound is 7-{[3-(3-Chloro-phenyl)-propyl]-methanesulfonyl-amino}-heptanoic acid, 7-{[3-(3,5-Dichloro-phenyl)-propyl]-methanesulfonyl-amino}-heptanoic acid or 5-(3-{[3-(3-Chloro-phenyl)-propyl]-methanesulfonyl-amino}-propyl)-thiophene -2- carboxylic acid. 29. A compound as recited in claim 8 wherein Q is -(C.sub.2 -C.sub.6)alkylene-W-(C.sub.1 -C.sub.3)alkylene-; and W is oxy. 30. A compound as recited in claim 8 wherein Q is -(C.sub.3 -C.sub.8)alkylene-, said -(C.sub.3 -C.sub.8)alkylene- optionally substituted with from one to four fluorines. 31. A compound as recited in claim 30 wherein A is methyl; Q is n-hexylene; Z is carboxyl; K is propylene; and M is 3-chlorophenyl. 32. A compound as recited in claim 30 wherein A is methyl; Q is n-hexylene; Z is carboxyl; K is propylene; and M is 3,5-dichlorophenyl. 33. A compound as recited in claim 8 wherein Q is -X-(C.sub.1 -C.sub.5)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 34. A compound as recited in claim 8 wherein Q is -(C.sub.1 -C.sub.5)alkylene-X-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 35. A compound as recited in claim 34 wherein A is methyl; Q-Z is 3-(2-carboxylthien-5-yl)-n-propylene K is propylene; and M is 3-chlorophenyl. 36. A compound as recited in claim 8 wherein Q is -(C.sub.1 -C.sub.3)alkylene-X-(C.sub.1 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 37. A compound as recited in claim 8 wherein Q is -(C.sub.2 -C.sub.4)alkylene-W-X-(C.sub.0 -C.sub.3)alkylene-; X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy; and W is oxy. 38. A compound as recited in claim 8 wherein Q is -(C.sub.0 -C.sub.4)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-; X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy; and W is oxy. 39. A compound as recited in claim 8 wherein Q is -(C.sub.2 -C.sub.4)alkylene-W-X-W-(C.sub.1 -C.sub.3)alkylene-; W is oxy; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 40. A compound as recited in claim 8 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-; and M is --Ar and --Ar is phenyl. 41. A compound as recited in claim 8 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-(C.sub.0 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 42. A compound as recited in claim 8 wherein Q is -(C.sub.1 -C.sub.3)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-; W is oxy; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 43. A compound as recited in claim 8 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-. 44. A compound as recited in claim 8 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-X-(C.sub.0 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 45. A compound as recited in claim 9 wherein the compound is 7-{[2-(3,5-Dichloro-phenoxy)-ethyl]-methanesulfonyl-amino}-heptanoic acid, 5-(3-{[2-(3,5-Dichloro-phenoxy)-ethyl]-methanesulfonyl-amino}-propyl)-thiop hene-2-carboxylic acid or N-[2-(3,5-Dichloro-phenoxy)-ethyl]-N- [6-(1H-tetrazol-5-yl)-hexyl]-methanesulfonamide. 46. A compound as recited in claim 9 wherein Q is -(C.sub.2 -C.sub.6)alkylene-W-(C.sub.1 -C.sub.3)alkylene-; and W is oxy. 47. A compound as recited in claim 9 wherein Q is -(C.sub.3 -C.sub.8)alkylene-, said -(C.sub.3 -C.sub.8)alkylene- optionally substituted with from one to four fluorines. 48. A compound as recited in claim 47 wherein A is methyl; Q is n-hexylene; Z is carboxyl; K is oxyethylene; and M is 3,5-dichlorophenyl. 49. A compound as recited in claim 9 wherein Q is -X-(C.sub.1 -C.sub.5)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 50. A compound as recited in claim 9 wherein Q is -(C.sub.1 -C.sub.5)alkylene-X-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 51. A compound as recited in claim 50 wherein A is methyl; Q-Z is 3-(2-carboxylthien-5-yl)-n-propylene; K is oxyethylene; and M is 3,5-dichlorophenyl. 52. A compound as recited in claim 9 wherein Q is -(C.sub.1 -C.sub.3)alkylene-X-(C.sub.1 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 53. A compound as recited in claim 9 wherein Q is -(C.sub.2 -C.sub.4)alkylene-W-X-(C.sub.0 -C.sub.3)alkylene-; X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy; and W is oxy. 54. A compound as recited in claim 9 wherein Q is -(C.sub.0 -C.sub.4)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-; X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy; and W is oxy. 55. A compound as recited in claim 9 wherein Q is -(C.sub.2 -C.sub.4)alkylene-W-X-W-(C.sub.1 -C.sub.3)alkylene-; W is oxy; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 56. A compound as recited in claim 9 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-; and M is --Ar and --Ar is phenyl. 57. A compound as recited in claim 9 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-(C.sub.0 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 58. A compound as recited in claim 9 wherein Q is -(C.sub.1 -C.sub.3)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-; W is oxy; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 59. A compound as recited in claim 9 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-. 60. A compound as recited in claim 9 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-X-(C.sub.0 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 61. A compound as recited in claim 7 wherein A is (C.sub.1 -C.sub.3)alkyl; K is (C.sub.3 -C.sub.8)alkylene, said (C.sub.3 -C.sub.8)alkylene being mono-unsaturated; --Ar is phenyl cyclopentyl or cyclohexyl; and R.sup.1, R.sup.2 and R.sup.3 are each independently hydroxy, halo, trifluoromethyl, difluoromethoxy, trifluoromethoxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.7)alkyl. 62. A compound as recited in claim 61 wherein the compound is Trans-(4-{[3-(3,5-Dichloro-phenyl)-allyl]-methanesulfonyl-amino}-butoxy)-ac etic acid, Trans-N-[3-(3,5-Dichloro-phenyl)-allyl]-N-[6-(1H-tetrazolyl-5-yl)-hexyl]-me thanesulfonamide, Trans-5-(3-{[3-(3,5-Dichloro-phenyl)-allyl]-methanesulfonyl-amino}-propyl)- thiophene-2-carboxylic acid or Trans-[3-({[3-(3,5-Dichloro-phenyl)-allyl]-methanesulfonyl-amino}-methyl)-p henyl]-acetic acid. 63. A compound as recited in claim 61 wherein Q is -(C.sub.2 -C.sub.6)alkylene-W-(C.sub.1 -C.sub.3)alkylene-; and W is oxy. 64. A compound as recited in claim 63 wherein A is methyl; Q is methyloxy-n-butylene; Z is carboxyl; K is trans-2-n-propenylene; and M is 3,5-dichlorophenyl. 65. A compound as recited in claim 61 herein Q is -(C.sub.3 -C.sub.8)alkylene-, said -(C.sub.3 -C.sub.8)alkylene- optionally substituted with from one to four fluorines. 66. A compound as recited in claim 65 wherein A is methyl; Q is n-hexylene; Z is 5-(1H-tetrazolyl); K is trans-2-n-propenylene; and M is 3,5-dichlorophenyl. 67. A compound as recited in claim 61 wherein Q is -X-(C.sub.1 -C.sub.5)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 68. A compound as recited in claim 61 wherein Q is -(C.sub.1 -C.sub.5)alkylene-X-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 69. A compound as recited in claim 68 wherein A is methyl; Q-Z is 3-(2-carboxylthien-5-yl)-n-propylene; K is trans-2-n-propenylene; and M is 3,5-dichlorophenyl. 70. A compound as recited in claim 61 wherein Q is -(C.sub.1 -C.sub.3)alkylene-X-(C.sub.1 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 71. A compound as recited in claim 61 werein Q is -(C.sub.2 -C.sub.4)alkylene-W-X-(C.sub.0 -C.sub.3)alkylene-; X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy; and W is oxy. 72. A compound as recited in claim 61 wherein Q is -(C.sub.0 -C.sub.4)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-; X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy; and W is oxy. 73. A compound as recited in claim 61 wherein Q is -(C.sub.2 -C.sub.4)alkylene-W-X-W-(C.sub.1 -C.sub.3)alkylene-; W is oxy; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 74. A compound as recited in claim 61 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-; and M is --Ar and --Ar is phenyl. 75. A compound as recited in claim 61 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-(C.sub.0 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 76. A compound as recited in claim 61 wherein Q is -(C.sub.1 -C.sub.3)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-; W is oxy; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 77. A compound as recited in claim 61 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-. 78. A compound as recited in claim 61 wherein Q is -(C.sub.1 -C.sub.4)alkylene-ethenylene-X-(C.sub.0 -C.sub.3)alkylene-; and X is thienyl or phenyl; said phenyl and thienyl optionally mono- or di-substituted independently with fluoro, chloro, trifluoromethyl or methoxy. 79. A compound as recited in claim 47 wherein A is methyl; Q is n-hexylene; Z is 5-(1H-tetrazolyl); K is oxyethyl; and M is 3,5-dichlorophenyl. 80. A compound as recited in claim 70 wherein A is methyl; Q is 3-methylenephenylmethyl; Z is carboxyl; K is trans-2-n-propenylene; and M is 3,5-dichlorophenyl. 81. A method for treating a mammal having a condition which presents with low bone mass comprising administering to said mammal a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof. 82. The method as recited in claim 81 wherein osteoporosis, osteotomy, childhood idiopathic bone loss or bone loss associated with periodontitis is treated. 83. The method as recited in claim 82 wherein osteoporosis is treated in a human. 84. The method as recited in claim 81 wherein glucocorticoid-induced osteoporosis, hyperthyroidism-induced osteoporosis, immobilization-induced osteoporosis, heparin-induced osteoporosis or immunosuppressive-induced osteoporosis is treated. 85. A method for augmenting and maintaining bone mass in a mammal comprising administering to a mammal a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable or prodrug thereof. 86. The method as recited in claim 85 wherein bone healing following facial reconstruction, maxillary reconstruction or mandibular reconstruction is treated, vertebral synostosis is induced or long bone extension is enhanced, the healing rate of a bone graft is enhanced or prosthetic ingrowth is enhanced. 87. The method as recited in claim 85 wherein a bone fracture is treated in a human. 88. A pharmaceutical composition which comprises a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier. 89. The pharmaceutical composition as recited in claim 88 for the treatment of osteoporosis wherein the therapeutically effective amount is an osteoporosis treating amount. 90. A pharmaceutical composition for the augmentation of bone mass which comprises a bone mass augmenting amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier. 91. The pharmaceutical composition as recited in claim 90 for the treatment of a bone fracture wherein a bone fracture treating amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof is used. 92. A pharmaceutical composition for the treatment of a condition which presents with low bone mass in a mammal which comprises a low bone mass condition treating amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier. 93. A pharmaceutical composition comprising: a. a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof; b. a therapeutically effective amount of an anti-resolve agent; and c. a pharmaceutical carrier. 94. A pharmaceutical composition as recited in claim 93 wherein the anti-resorptive agent is droloxifene, raloxifene, tamoxifen, 4-hydroxy-tamoxifen, toremifene, centchroman, levormeloxifene, idoxifene, 6-(4-hydroxy-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-o l, {4-[2-(2-Aza-bicyclo[2.2. 1]hept-2-yl)-ethoxy]-phenyl}-[6-hydroxy-2-(4-hydroxy-phenyl)-benzo[b]thiop hen-3-yl]-methanone, Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetr ahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro -naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-nap hthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrahyd rohaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4"-fluorophenyl)-6-hydroxy-1,2,3,4-tetrah ydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetr ahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoqui noline or a pharmaceutically acceptable salt thereof. 95. A pharmaceutical composition as recited in claim 93 wherein the anti-resorptive agent is tiludronic acid, alendronic acid, ibandronic acid, risedronic acid, etidronic acid, clodronic acid, and pamidronic acid or a pharmaceutically acceptable salt thereof. 96. A method for treating a mammal having a condition which presents with low bone mass comprising administering to said mammal a. a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof; and b. a therapeutically effective amount of an anti-resorptive agent. 97. The method as recited in claim 96 wherein the anti-resorptive agent is droloxifene, raloxifene, tamoxifen, 4-hydroxy-tamoxifen, toremifene, centchroman, levormeloxifene, idoxifene, 6-(4-hydroxy-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-o l, {4-[2-(2-Aza-bicyclo[2.2. 1]hept-2-yl)-ethoxy]-phenyl}-[6-hydroxy-2-(4-hydroxy-phenyl)-benzo[b]thiop hen-3-yl]-methanone, Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetr ahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro -naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro-nap hthalene-2-ol; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrahyd rohaphthatene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4"-fluorophenyl)-6-hydroxy-1,2,3,4-tetrah ydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetr ahydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoqui noline or a pharmaceutically acceptable salt thereof. 98. The method as recited in claim 96 wherein the anti-resorptive agent is, tiludronic acid, alendronic acid, ibandronic acid, risedronic acid, etidronic acid, clodronic acid, and pamidronic acid or a pharmaceutically acceptable salt. 99. A kit comprising: a. a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier in a first unit dosage form; b. a therapeutically effective amount of an anti-resorptive agent and a pharmaceutically acceptable carrier in a second unit dosage form; and c. container means for containing soi first and second dosage forms. 100. The kit as recited in claim 99 wherein the anti-resorptive agent is droloxifene, raloxifene, tamoxifen, 4-hydroxy-tamoxifen, toremifene, centchroman, levormeloxifene, idoxifene, 6-(4-hydroxy-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzyl]-naphthalen-2-o l, {4-[2-(2-Aza-bicydo[2.2. 1]hept-2-yl)-ethoxy]-phenyl}-[6-hydroxy-2-(4-hydroxy-phenyl)-benzo[b]thiop hen-3-yl]-methanone, Cis-6-(4-fluoro-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetr ahydro-naphthalene-2-ol; (-)-Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydro -naphthalene-2-ol; Cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydr-onap hthalene-2-ot; Cis-1-[6'-pyrrolodinoethoxy-3'-pyridyl]-2-phenyl-6-hydroxy-1,2,3,4-tetrahyd rohaphthalene; 1-(4'-Pyrrolidinoethoxyphenyl)-2-(4"-fluorophenyl)-6-hydroxy-1,2,3,4-tetrah ydroisoquinoline; Cis-6-(4-hydroxyphenyl)-5-[4-(2-pipeddin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetra hydro-naphthalene-2-ol; or 1-(4'-Pyrrolidinolethoxyphenyl)-2-phenyl-6-hydroxy-1,2,3,4-tetrahydroisoqui noline or a pharmaceutically acceptable salt thereof. 101. The kit as recited in 99 wherein the anti-resorptive agent is tiludronic acid, alendronic acid, ibandronic acid, risedronic acid, etidronic acid, clodronic acid, and pamidronic acid or a pharmaceutically acceptable salt thereof. 102. A pharmaceutical composition comprising: a. a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof; b. a therapeutically effective amount of an anabolic agent other than a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof; and c. a pharmaceutical carrier. 103. The pharmaceutical composition as recited in claim 102 wherein the anabolic agent other than the claim 1 compound is IGF-1 optionally with IGF-1 binding protein 3 prostaglandin, prostaglandin agonist/antagonist, sodium fluoride, parathyroid hormone (PTH), active fragments of parathyroid hormone, growth hormone or growth hormone secretagogues or a pharmaceutically acceptable salt thereof. 104. A method for treating a mammal which presents with low bone mass comprising administering to said a. a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof; and b. a therapeutically effective amount of a bone anabolic agent other than a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof. 105. The method as recited in claim 104 wherein the anabolic agent other than the claim 1 compound is IGF-1, prostaglandin, prostaglandin agonist/antagonist, sodium fluoride, parathyroid hormone (PTH), active fragments of parathyroid hormone, growth hormone or growth hormone secretagogues or a pharmaceutically acceptable salt thereof. 106. A kit comprising: a. a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier in a first unit dosage form; b. a therapeutically effective amount of an anabolic agent other than a compound of claim 1 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier in a second unit dosage form; and c. container means for containing said first and second dosage forms. 107. The kit as recited in claim 106 wherein the anabolic agent other than the claim 1 compound is IGF-1, prostaglandin, prostaglandin agonist/antagonist, sodium fluoride, parathyroid hormone (PTH), active fragments of parathyroid hormone, growth hormone or growth hormone secretagogues or a pharmaceutically acceptable salt thereof. 108. A compound as recited in claim 1 wherein A is (C.sub.1 -C.sub.3)alkyl; Q is --(C.sub.3 -C.sub.5)alkylene-O-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.5 -C.sub.7)alkylene-, said -(C.sub.5 -C.sub.7)alkylene- optionally substituted with up to four substituents independently selected from fluoro or (C.sub.1 -C.sub.4)alkyl, --(C.sub.2 -C.sub.4)alkylene-X-, --(CH.sub.2)-meta-phenylene-O--(CH.sub.2)- optionally mono- or di-substituted independently with methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, chloro or fluoro or --(CH2)-meta-phenylene-(CH.sub.2)- optionally mono- or di-substituted independently with methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, chloro or fluoro; M is --Ar.sup.1 --V--Ar.sup.2 or --Ar.sup.1 --O--Ar.sup.2 ; V is a bond or --CH.sub.2 --; Z is carboxyl, (C.sub.1 -C.sub.4)alkoxycarbonyl or tetrazolyl; X is thienyl, thiazolyl, or furanyl; K is methylene; Ar.sup.1 is phenyl or (C.sub.5 -C.sub.7)cycloalkyl; Ar.sup.2 is (C.sub.5 -C.sub.7)cycloalkyl or phenyl; R.sup.1 is chloro, fluoro, (C.sub.1 -C.sub.4)alkyl or (C.sub.1 -C.sub.4)alkoxy, said (C.sub.1 -C.sub.4)alkyl and (C.sub.1 -C.sub.4)alkoxy optionally mono-, di- or tri-substituted independently with hydroxy or fluoro; and R.sup.2 and R.sup.3 are each independently, methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, chloro or fluoro. 109. A compound as recited in claim 108 wherein Q is --(CH2)-meta-phenylene-(CH.sub.2)-, M is --Ar.sup.1 --Ar.sup.2, Ar.sup.1 is phenyl; Ar.sup.2 is (C.sub.5 -C.sub.7)cycloalkyl or phenyl said Ar.sup.2 optionally mono- or di-substituted independently with R.sup.1 or R.sup.2 ; R.sup.1 is chloro, fluoro, methyl, methoxy, trifluoromethyl, difluoromethoxy or trifluoromethoxy; and R.sup.2 is methoxy, chloro or fluoro. 110. A compound as recited in claim 108 wherein Q is --(CH2)-meta-phenylene-O-(CH.sub.2)-, M is --Ar.sup.1 --Ar.sup.2, Ar.sup.1 is phenyl; Ar.sup.2 is (C.sub.5 -C.sub.7)cycloalkyl or phenyl said Ar.sup.2 optionally mono- or di-substituted independently with R.sup.1 or R.sup.2 ; R.sup.1 is chloro, fluoro, methyl, methoxy, trifluoromethyl, difluoromethoxy or trifluoromethoxy; and R.sup.2 is methoxy, chloro or fluoro. 111. A compound of claim 109 wherein A is methyl; Z is carboxyl; and M is 4-(cyclohexyl)phenyl. 112. A compound as recited in claim 109 wherein the compound is (3-{[(4-Cyclohexyl-benzyl)-methanesulfonyl-amino]-methyl}-phenyl)-acetic acid. 113. A compound as recited in claim 1 wherein A is (C.sub.1 -C.sub.3)alkyl; Q is -(C.sub.2 -C.sub.4)alkylene-X-; X is thiazolyl or furanyl; said thiazolyl or fuiranyl optionally mono- or di-substituted independently with methyl, methoxy, fluoro, chloro, trifluoromethyl, difluoromethoxy or trifluoromethoxy; K is oxy-ethylene or propylene, said propylene optionally being mono-unsaturated; M is --Ar, said --Ar is phenyl, cyclohexyl, cyclopentyl, cyclobutyl, or cycloheptyl; R.sup.1 is halo, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.7)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.1 -C.sub.7)alkanoyl or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, said (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.7)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.1 -C.sub.7)alkanoyl or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, optionally mono-, di- or tri-substituted independently with hydroxy, fluoro or chloro; and R.sup.2 and R.sup.3 are each independently methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy, chloro or fluoro. 114. A compound as recited in claim 113 wherein A is methyl; Z is carboxyl, or (C.sub.1 -C.sub.4)alkoxycarbonyl; Q is -propylene-X-; X is thiazolyl; K is oxy-ethylene or propylene; M is phenyl optionally mono- or di-substituted independently with fluoro, chloro, methoxy, methyl, difluoromethoxy, trifluoromethoxy or trifluoromethyl. 115. A compound as recited in claim 114 wherein Z is carboxyl; K is propylene; and M is 3-(chloro)phenyl. 116. A compound as recited in claims 114 wherein Z is carboxyl; K is oxy-ethylene; and M is 3,5-dichlorophenyl. 117. A compound as recited 113 in claim wherein the compound is a. 2-(3-{[2-(3,5-Dichloro-phenoxy)-ethyl]-methanesulfonyl-amino}-propyl)-thia zole-4-carboxylic acid or b. 2-(3-{[3-(3-Chloro-phenyl)-propyl]-methanesulfonyl-amino}-propyl)-thiazole -4-carboxylic acid. 118. A compound having the Formula IA ##STR31## or a pharmaceutically acceptable salt or prodrug thereof wherein A is (C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.7)cycloalkyl or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.6)alkyl, said A moieties optionally mono-, di- or tri-substituted on carbon independently with hydroxy, (C.sub.1 -C.sub.4)alkyl or halo; Q is --(C.sub.2 -C.sub.6)alkylene-W-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.3 -C.sub.8)alkylene-, said -(C.sub.3 -C.sub.8)alkylene- being straight chain with the proviso that (C.sub.3 -C.sub.8)alkylene may optionally substituted with up to four substituents independently selected from fluoro or (C.sub.1 -C.sub.4)alkyl, --X-(C.sub.1 -C.sub.5)alkylene-, --(C.sub.1 -C.sub.5)alkylene-X-, --(C.sub.1 -C.sub.3)alkylene-X-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.2 -C.sub.4)alkylene-W-X-(C.sub.0 -C.sub.3)alkylene-, --(C.sub.0 -C.sub.4)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.2 -C.sub.5)alkylene-W-X-W-(C.sub.1 -C.sub.3)alkylene-, wherein the two occurrences of W are independent of each other, --(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-, --(C.sub.1 --C.sub.4)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-(C.sub.0 -C.sub.5)alkylene-, --(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.0 -C.sub.2)alkylene-X-W-(C.sub.1 -C.sub.3)alkylene-, --(C.sub.1 -C.sub.4)alkylene-ethenylene-(C.sub.1 -C.sub.4)alkylene-, or --(C.sub.1 -C.sub.4)alkylene-ethenylene-X-(C.sub.0 -C.sub.3)alkylene-; W is oxy, thio, sulfino, sulfonyl, aminosulfonyl-, -mono-N-(C.sub.1 -C.sub.4)alkyleneaminosulfonyl-, sulfonylamino, N-(C.sub.1 -C.sub.4)alkylenesulfonylamino, carboxamido, N-(C.sub.1 -C.sub.4)alkylenecarboxamido, carboxamidooxy, N-(C.sub.1 -C.sub.4)alkylenecarboxamidooxy, carbamoyl, -mono-N-(C.sub.1 -C.sub.4)alkylenecarbamoyl, carbamoyloxy, or -mono-N-(C.sub.1 -C.sub.4)alkylenecarbamoyloxy, wherein said W alkyl groups are optionally substituted on carbon with one to three fluorines; X is tetrahydrofuranyl or a five or six membered aromatic ring optionally having one or two heteroatoms selected independently from oxygen, nitrogen, and sulfur; said ring optionally mono-, or di-substituted independently with halo, (C.sub.1 -C.sub.3)alkyl, trifluoromethyl, trifluoromethyloxy, difluoromethyloxy, hydroxyl, (C.sub.1 -C.sub.4)alkoxy, or carbamoyl; Z is carboxyl, (C.sub.1 -C.sub.6)alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl, 5-oxo-1,2,4-oxadiazolyl, 5-oxo-1,2,4-thiadiazolyl, (C.sub.1 -C.sub.4)alkylsulfonylcarbamoyl or phenylsulfonylcarbamoyl; K is a bond, (C.sub.1 -C.sub.8)alkylene, thio(C.sub.1 -C.sub.4)alkylene or oxy(C.sub.1 -C.sub.4)alkylene, said (C.sub.1 -C.sub.8)alkylene optionally mono-unsaturated and wherein K is optionally mono-, di- or tri-substituted independently with fluoro, methyl or chloro; M is --Ar, --Ar.sup.1 -V--Ar.sup.2, --Ar.sup.1 -S--Ar.sup.2, --Ar.sup.1 -O--Ar.sup.2, --Ar.sup.1 -S-(C.sub.1 -C.sub.3)--Ar.sup.2 --, --Ar.sup.1 -(C.sub.1 -C.sub.3)-S-Ar.sup.2 - or --Ar.sup.1 -(C.sub.1 -C.sub.3)-S-(C.sub.1 -C.sub.3)--Ar.sup.2, wherein Ar, Ar.sup.1 and Ar.sup.2 are each independently a partially saturated, fully saturated or fully unsaturated five to eight membered ring, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated five or six membered rings, taken independently; said Ar, Ar.sup.1 and Ar.sup.2 moieties optionally substituted, on one ring if the moiety is monocyclic, or one or both rings if the moiety is bicyclic, on carbon, nitrogen or sulfur with up to three substituents independently selected from R.sup.1, R.sup.2 and R.sup.3 wherein R.sup.1, R.sup.2 and R.sup.3 are oxo, hydroxy, nitro, halo, (C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.4)alkoxy(C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxycarbonyl, (C.sub.1 -C.sub.7)alkyl, (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkyl, (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.4)alkanoyl, formyl, (C.sub.1 -C.sub.8)alkanoyl, (C.sub.1 -C.sub.6)alkanoyl(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.4)alkanoylamino, (C.sub.1 -C.sub.4)alkoxycarbonylamino, sulfonamido, (C.sub.1 -C.sub.4)alkylsulfonamido, amino, mono-N- or di-N,N-(C.sub.1 -C.sub.4)alkylamino, carbamoyl, mono-N- or di-N,N-(C.sub.1 -C.sub.4)alkylcarbamoyl, cyano, thiol, (C.sub.1 -C.sub.6)alkylthio, (C.sub.1 -C.sub.6)alkylsulfinyl, (C.sub.1 -C.sub.4)alkylsulfonyl or mono-N- or di-N,N-(C.sub.1 -C.sub.4)alkylaminosulfinyl; R.sup.1, R.sup.2 and R.sup.3 are optionally mono-, di- or tri-substituted on carbon independently with halo or hydroxy; and V is a bond or (C.sub.1 -C.sub.3)alkylene optionally mono-unsaturated and optionally mono- or di-substituted independently with hydroxy or fluoro, with the proviso that when K is (C.sub.2 -C.sub.4)alkylene and M is Ar and Ar is cyclopent-1-yl, cyclohex-1-yl, cyclohept-1-yl or cyclooct-1-yl then said (C.sub.5 -C.sub.8)cycloalkyl substituents are not substituted at the one position with hydroxy. 119. A pharmaceutical composition comprising: a. a therapeutically effective amount of a compound of claim 118 or a pharmaceutically acceptable salt or prodrug thereof; b. a therapeutically effective amount of 2-(4-methoxy-phenyl)-3-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-benzo[b]thiop hen-6-ol or a pharmaceutically acceptable salt thereof or 3-[4-(1,2-diphenyl-but-1-enyl)-phenyl]-acrylic acid or a pharmaceutically acceptable salt thereof and c. a pharmaceutical carrier. 120. A method for treating a mammal having a condition which presents with low bone mass comprising administering to said mammal a. a therapeutically effective amount of a compound of claim 118 or a pharmaceutically acceptable salt or prodrug thereof; and b. a therapeutically effective amount of 2-(4-methoxy-phenyl)-3-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-benzo[b]thiop hen-6-ol or a pharmaceutically acceptable salt thereof or 3-[4-(1,2-diphenyl-but-1-enyl)-phenyl]-acrylic acid or pharmaceutically acceptable salt thereof. 121. A kit comprising: a. a therapeutically effective amount of a compound of claim 118 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier in a first unit dosage form; b. a therapeutically effective amount of 2-(4-methoxy-phenyl)-3-[4-(2-piperidin-1-yl-ethoxy)-phenoxy]-benzo[b]thiop hen-6-ol or a pharmaceutically acceptable salt thereof or 3-[4-(1,2-diphenyl-but-1-enyl)-phenyl]-acrylic acid or a pharamceutically acceptable salt thereof and a pharmaceutically acceptable carrier in a second unit dosage form; and c. container means for containing said first and second dosage forms. 122. A method for treating a mammal in need of kidney regeneration comprising administering to said mammal a therapeutically effective amount of a compound of claim 118 or a pharmaceutically acceptable salt or prodrug thereof. 123. A method for treating a mammal having a condition which presents with low bone mass comprising administering to said mammal a therapeutically effective amount of a compound of claim 118 or a pharmaceutically acceptable salt or prodrug thereof. 124. A pharmaceutical composition which comprises a therapeutically effective amount of a compound of claim 118 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier.

Details for Patent 6,288,120

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Nps Pharmaceuticals, Inc.	NATPARA	parathyroid hormone	For Injection	125511	01/23/2015		2016-12-20