Claims for Patent: 6,492,412

Summary for Patent: 6,492,412

Title:	Prevention of loss and restoration of bone mass by certain prostaglandin agonists
Abstract:	Prostaglandin agonists, methods of using such prostaglandin agonists, pharmaceutical compositions containing such prostaglandin agonists and kits containing such prostaglandin agonists. The prostaglandin agonists are useful for the treatment of bone disorders including osteoporosis.
Inventor(s):	Cameron; Kimberly O. (East Lyme, CT), Ke; Hua Z. (Ledyard, NY), 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:	09/897,824
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.8)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-ethynylene--(C.sub.1 -C.sub.4)alkylene-, or --(C.sub.1 -C.sub.4)alkylene-ethynylene-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, 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 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 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 having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or, a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated five or six membered rings, taken independently, having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen; 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. 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 thienyl, thiazolyl, pyridyl, pyrimidyl, oxazolyl, furanyl, imidazolyl, isoxazolyl, pyrazinyl or pyrazolyl; 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 independently pyridyl or thienyl; 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 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 thienyl, pyridyl, thiazolyl, oxazolyl, isoxazolyl, benzo[b]furanyl, benzo[b]thiophenyl, indanyl, furanyl, benzo[1,3]dioxolyl, benzimidazolyl, benzisoxazolyl, 2,3-dihydrobenzo[1,4]dioxinyl, 2,3-dihydrobenzofuranyl, pyrazolyl, pyrimidyl, imidazolyl, quinolinyl, isoquinolinyl, benzoxazolyl, benzothiazolyl, indolyl, or chromanyl; 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. 5. A compound as recited in claim 4 wherein K is methylene; A is (C.sub.1 -C.sub.3)alkyl; M is --Ar and --Ar is thiazolyl, pyridyl, thienyl, oxazolyl, furanyl, 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. 6. A compound as recited in claim 5 wherein the compound is 7-{[5-(1-Hydroxy-hexyl)-thiopen-2-ylmethyl]-methanesulfonyl-amino{-heptanoi c acid. 7. A compound as recited in claim 5 wherein Q is --(C.sub.2 -C.sub.6)alkylene-W--(C.sub.1 -C.sub.3)alkylene-; and W is oxy. 8. A compound as recited in claim 5 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. 9. A compound as recited in claim 8 wherein A is methylsulfonyl; Q is n-hexylene; Z is carboxyl; K is methylene; and M is 5-(1-hydroxy-n-hexylene-1-yl)thien-2-yl. 10. A compound as recited in claim 5 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. 11. A compound as recited in claim 5 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. 12. A compound as recited in claim 5 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. 13. A compound as recited in claim 5 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. 14. A compound as recited in claim 5 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. 15. A compound as recited in claim 5 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. 16. A compound as recited in claim 5 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 thiazolyl, pyridyl or thienyl. 17. A compound as recited in claim 5 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. 18. A compound as recited in claim 5 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. 19. A compound as recited in claim 5 wherein Q is --(C.sub.1 -C.sub.4)alkylene-ethynylene--(C.sub.1 -C.sub.4)alkylene-. 20. A compound as recited in claim 5 wherein Q is --(C.sub.1 -C.sub.4)alkylene-ethynylene-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. 21. A compound as recited in claim 4 wherein A is (C.sub.1 -C.sub.3)alkyl; K is (C.sub.1 -C.sub.8)alkylene; --Ar is thiazolyl, pyridyl, thienyl, benzofuranyl, benzo[1,3]dioxolyl, 2,3-dihydrobenzo[1,4]dioxine, 2,3-dihydrobenzofuranyl, benzimidazolyl, or benzo[b]thiophenyl; 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. 22. A compound as recited in claim 21 wherein Q is --(C.sub.2 -C.sub.6)alkylene-W--(C.sub.1 -C.sub.3)alkylene-; and W is oxy. 23. A compound as recited in claim 21 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. 24. A compound as recited in claim 21 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. 25. A compound as recited in claim 21 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. 26. A compound as recited in claim 21 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. 27. A compound as recited in claim 21 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. 28. A compound as recited in claim 21 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. 29. A compound as recited in claim 21 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. 30. A compound as recited in claim 21 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 thiazolyl, pyridyl or thienyl. 31. A compound as recited in claim 21 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. 32. A compound as recited in claim 21 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. 33. A compound as recited in claim 21 wherein Q is --(C.sub.1 -C.sub.4)alkylene-ethynylene--(C.sub.1 -C.sub.4)alkylene-. 34. A compound as recited in claim 21 wherein Q is --(C.sub.1 -C.sub.4)alkylene-ethynylene-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. 35. A compound as recited in claim 4 wherein A is (C.sub.1 -C.sub.3)alkyl; K is oxy(C.sub.1 -C.sub.4)alkylene; --Ar is thienyl, thiazolyl, pyridyl or benzo[1,3]dioxolyl; 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. 36. A compound as recited in claim 35 wherein Q is --(C.sub.2 -C.sub.6)alkylene-W--(C.sub.1 -C.sub.3)alkylene-; and w is oxy. 37. A compound as recited in claim 35 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. 38. A compound as recited in claim 35 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. 39. A compound as recited in claim 35 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. 40. A compound as recited in claim 35 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. 41. A compound as recited in claim 35 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. 42. A compound as recited in claim 35 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. 43. A compound as recited in claim 35 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. 44. A compound as recited in claim 35 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 thiazolyl, pyridyl or thienyl. 45. A compound as recited in claim 35 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. 46. A compound as recited in claim 35 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. 47. A compound as recited in claim 35 wherein Q is --(C.sub.1 -C.sub.4)alkylene-ethynylene--(C.sub.1 -C.sub.4)alkylene-. 48. A compound as recited in claim 35 wherein Q is --(C.sub.1 -C.sub.4)alkylene-ethynylene-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. 49. A compound as recited in claim 4 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 thienyl, thiazolyl, pyridyl, 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. 50. A compound as recited in claim 49 wherein Q is --(C.sub.2 -C.sub.6)alkylene-W--(C.sub.1 -C.sub.3)alkylene-; and W is oxy. 51. A compound as recited in claim 49 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. 52. A compound as recited in claim 49 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. 53. A compound as recited in claim 49 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. 54. A compound as recited in claim 49 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. 55. A compound as recited in claim 49 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. 56. A compound as recited in claim 49 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. 57. A compound as recited in claim 49 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. 58. A compound as recited in claim 49 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 thiazolyl, pyridyl or thienyl. 59. A compound as recited in claim 49 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. 60. A compound as recited in claim 49 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. 61. A compound as recited in claim 49 wherein Q is --(C.sub.1 -C.sub.4)alkylene-ethynylene--(C.sub.1 -C.sub.4)alkylene-. 62. A compound as recited in claim 49 wherein Q is --(C.sub.1 -C.sub.4)alkylene-ethynylene-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. 63. 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. 64. The method as recited in claim 63 wherein osteoporosis, osteotomy, childhood idiopathic bone loss or bone loss associated with periodontitis is treated. 65. The method as recited in claim 64 wherein osteoporosis is treated in a human. 66. The method as recited in claim 63 wherein glucocorticoid-induced osteoporosis, hyperthyroidism-induced osteoporosis, immobilization-induced osteoporosis, heparin-induced osteoporosis or immunosuppressive-induced osteoporosis is treated. 67. 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 salt or prodrug thereof. 68. The method as recited in claim 67 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. 69. The method as recited in claim 67 wherein a bone fracture is treated in a human. 70. 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. 71. The pharmaceutical composition as recited in claim 70 for the treatment of osteoporosis wherein the therapeutically effective amount is an osteoporosis treating amount. 72. 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. 73. The pharmaceutical composition as recited in claim 72 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. 74. 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. 75. 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-resorptive agent; and c. a pharmaceutical carrier. 76. A pharmaceutical composition as recited in claim 75 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-tetrahydronaph thalene-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. 77. A pharmaceutical composition as recited in claim 75 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. 78. 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. 79. The method as recited in claim 78 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-tetrahydronaph thalene-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. 80. The method as recited in claim 78 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. 81. 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 said first and second dosage forms. 82. The kit as recited in claim 81 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]thioph en-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-tetrahydronaph thalene-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. 83. The kit as recited in 81 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. 84. 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. 85. The pharmaceutical composition as recited in claim 84 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. 86. 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. 87. The method as recited in claim 86 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. 88. 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. 89. The kit as recited in claim 88 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. 90. 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 --(CH.sub.2)-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 furanyl, thienyl, thiazolyl, or pyridyl; Ar.sup.2 is thienyl, thiazolyl, pyridyl, pyrimidyl, oxazolyl, furanyl, imidazolyl, isoxazolyl, pyrazinyl, triazolyl or pyrazolyl; 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. 91. A compound as recited in claim 90 wherein Q is --(CH.sub.2)-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, phenyl, thienyl, thiazolyl, pyridyl, pyrimidyl, oxazolyl, furanyl, imidazolyl, isoxazolyl, pyrazinyl or pyrazolyl, 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. 92. A compound as recited in claim 90 wherein Q is --(CH.sub.2)-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, phenyl, thienyl, thiazolyl, pyridyl, pyrimidyl, oxazolyl, furanyl, imidazolyl, isoxazolyl, pyrazinyl or pyrazolyl, 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. 93. A compound of claim 91 wherein A is methylsulfonyl; Z is carboxyl; and M is 4-(cyclohexyl)phenyl. 94. A compound of claim 91 wherein A is methylsulfonyl; Z is carboxyl; and M is 4-(thiazol-2-yl)phenyl. 95. A compound of claim 91 wherein A is methylsulfonyl; Z is carboxyl; and M is 4-(pyrazin-2-yl)phenyl. 96. A compound as recited in claim 91 wherein the compound is a. (3-{[(4-Cyclohexyl-benzyl)-methanesulfonyl-amino]-methyl}-phenyl)-acetic acid; b. (3-{[Methanesulfonyl-(4-thiazol-2-yl-benzyl)-amino]-methyl}-phenyl)-acetic acid; or c. (3-{[Methanesulfonyl-(4-pyrazin-2-yl-benzyl)-amino]-methyl}-phenyl)-acetic acid. 97. 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 furanyl 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 thienyl, pyridyl, thiazolyl, oxazolyl, isoxazolyl, pyrimidyl or imidazolyl; 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. 98. 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-ethynylene--(C.sub.1 -C.sub.4)alkylene-, or --(C.sub.1 -C.sub.4)alkylene-ethynylene-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--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 having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated five or six membered rings, taken independently, having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen; 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. 99. A pharmaceutical composition comprising: a. a therapeutically effective amount of a compound of claim 98 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. 100. 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 98 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. 101. A kit comprising: a. a therapeutically effective amount of a compound of claim 98 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. 102. 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 98 or a pharmaceutically acceptable salt or prodrug thereof. 103. 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 98 or a pharmaceutically acceptable salt or prodrug thereof. 104. A pharmaceutical composition which comprises a therapeutically effective amount of a compound of claim 98 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier.

Details for Patent 6,492,412

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