Claims for Patent: 6,649,657

Summary for Patent: 6,649,657

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, 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:	10/256,985
Patent Claims:	1. A compound having the Formula I ##STR28## or a pharmaceutically acceptable salt or prodrug thereof wherein either B is N; A is (C.sub.1 -C.sub.6)alkanoyl, or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.6)alkanoyl, said A moieties optionally mono-, di- or tri- substituted independently on carbon with hydroxy or halo; 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- 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-, --(C.sub.0 -C.sub.4)alkylene-X--W--(C.sub.1 -C.sub.3)alkylene-, --(C.sub.2 -C.sub.4)alkylene-W--X--W--(C.sub.1 -C.sub.3)alkylene-, wherein the two occurences 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)alkylenesufonylamino, 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 phenylsulfonylcarbamoyl; K is (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 optionally 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, optionally 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 H, 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 independently on carbon 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 cycloct-1-yl then said (C.sub.5 -C.sub.8)cycloalkyl substituents are not substituted at the one position with hydroxy and with the proviso that 6-[(3-phenyl-propyl)-(2-propyl-pentanoyl)-amino]-hexanoic acid and its ethyl ester are not included or: B is C(H); A is (C.sub.1 -C.sub.6)alkanoyl, or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.6)alkanoyl, said A moieties optionally mono-, di- or tri-substituted on carbon independently with hydroxy or halo; 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- 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, 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 phenylsulfonylcarbamoyl; K is a bond, (C.sub.1 -C.sub.8)alkylene, thio(C.sub.1 -C.sub.4)alkylene, (C.sub.4 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.6)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 optionally 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, optionally 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 H, 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 B is N; A is (C.sub.1 -C.sub.6)alkanoyl, or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.6)alkanoyl, said A moieties optionally mono-, di- or tri-substituted on carbon independently with hydroxy or halo; 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 (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; Ar is (C.sub.5 -C.sub.7)cycloalkyl, phenyl, thienyl, pyridyl, thiazolyl, oxazolyl, isoxazolyl, naphthalenyl, 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, pyrazinyl, imidazolyl, quinolinyl, isoquinolinyl, benzoxazolyl, benzothiazolyl, indolyl, 1,2,3,4-tetrahydronaphthalenyl, cyclohexyl, cyclopentyl, or chromanyl; Ar.sup.1 and Ar.sup.2 are each independently (C.sub.5 -C.sub.7)cycloalkyl, phenyl, 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, (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, difluoromethoxy, trifluoromethoxy, 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 or carbamoyl. 3. A compound as recited in claim 2 wherein A is (C.sub.1 -C.sub.6)alkanoyl, said (C.sub.1 -C.sub.6)alkanoyl optionally mono-, di- or tri-substituted on carbon independently with halo; 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- 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-; K is methylene or ethylene; M is --Ar.sup.1 --V--Ar.sup.2 or --Ar.sup.1 --O--A.sup.2 wherein Ar.sup.1 and Ar.sup.2 are each independently phenyl, 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.6)alkoxy, said (C.sub.1 -C.sub.4)alkyl and (C.sub.1 -C.sub.6)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 2 wherein A is (C.sub.1 -C.sub.6)alkanoyl said (C.sub.1 -C.sub.6)alkanoyl optionally mono-, di- or tri-substituted independently on carbon with hydroxy or halo; K is methylene; 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- 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 and --Ar is phenyl, thiazolyl, pyridyl, thienyl, oxazolyl, furanyl, cyclopentyl or cyclohexyl wherein --Ar is substituted with at least R.sup.1 ; R.sup.2 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. 5. A compound as recited in claim 2 wherein A is (C.sub.1 -C.sub.6)alkanoyl said (C.sub.1 -C.sub.6)alkanoyl optionally mono-, di- or tri-substituted independently on carbon with halo; K is (C.sub.1 -C.sub.8)alkylene; 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- 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 and --Ar is phenyl, thienyl, benzofurahyl, benzo[1,3]dioxolyl, 2,3-dihydrobenzo[1,4]dioxinyl, 2,3-dihydrobenzofuranyl, benzimidazolyl, benzo[b]thiophenyl, 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. 6. A compound as recited in claim 2 wherein A is (C.sub.1 -C.sub.6)alkanoyl said (C.sub.1 -C.sub.6)alkanoyl optionally mono-, di- or tri-substituted on carbon independently with halo; K is oxy(C.sub.1 -C.sub.4)alkylene; 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- 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 and --Ar is phenyl, thienyl, benzo[1,3]dioxolyl, 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. 7. A compound as recited in claim 2 wherein A is (C.sub.3 -C.sub.6)alkanoyl said (C.sub.3 -C.sub.6)alkanoyl optionally mono-, di- or tri-substituted on carbon independently with halo; K is (C.sub.3 -C.sub.8)alkylene, said (C.sub.3 -C.sub.8)alkylene being mono-unsaturated; 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- 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 and --Ar is phenyl, thienyl, cyclopentyl or cyclohexyl; and R.sup.1, R.sup.2 and R.sup.3 are each independently hydroxy, halo, trifluoromethyl, trifluoromethoxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.7)alkyl. 8. A compound as recited in claim 1 wherein B is C(H); A is (C.sub.1 -C.sub.6)alkanoyl, or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.6)alkanoyl, said A moieties optionally mono-, di- or tri-substituted independently on carbon with hydroxy or halo; 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 (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 hydroxy, fluoro or chloro; Ar is (C.sub.5 -C.sub.7)cycloalkyl, phenyl, thienyl, pyridyl, thiazolyl, oxazolyl, isoxazolyl, naphthalenyl, 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, pyrazinyl, imidazolyl, quinolinyl, isoquinolinyl, benzoxazolyl, benzothiazolyl, indolyl, 1,2,3,4-tetrahydronaphthalenyl, cyclohexyl, cyclopentyl, or chromanyl; Ar.sup.1 and Ar.sup.2 are each independently (C.sub.5 -C.sub.7)cycloalkyl, phenyl, 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, (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, difluoromethoxy, trifluoromethoxy, 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 or carbamoyl. 9. A compound as recited in claim 8 wherein A is (C.sub.1 -C.sub.6)alkanoyl, said A optionally mono-, di- or tri-substituted on carbon independently with halo; 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- 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-; K is methylene or ethylene; 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 phenyl, pyridyl or thienyl; V is a bond or (C.sub.1 -C.sub.2)alkylene; R.sup.3 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. 10. A compound as recited in claim 8 wherein A is (C.sub.1 -C.sub.6)alkanoyl, said A optionally mono-, di- or tri-substituted on carbon independently with hydroxy or halo; K is methylene; 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- 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 and --Ar is phenyl, thiazolyl, pyridyl, thienyl, oxazolyl, furanyl, 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.6)alkoxy, said (C.sub.1 -C.sub.7)alkyl or (C.sub.1 -C.sub.6)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 8 wherein A is (C.sub.1 -C.sub.6)alkanoyl, said A optionally mono-, di- or tri-substituted on carbon independently with halo; K is (C.sub.1 -C.sub.8)alkylene; 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- 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 and --Ar is phenyl, thienyl, benzofuranyl, benzo[1,3]dioxolyl, 2,3-dihydrobenzo[1,4]dioxinyl, 2,3-dihydrobenzofuranyl, benzimidazolyl, benzo[b]thiophenyl, cyclopentyl or cyclohexyl; and R.sup.1, R.sup.2 and R.sup.3 are each independently hydroxy, halo, trifluoromethyl, trifluoromethoxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.7)alkyl. 12. A compound as recited in claim 8 wherein A is (C.sub.1 -C.sub.6)alkanoyl said A optionally mono-, di- or tri-substituted on carbon independently with halo; K is oxy(C.sub.1 -C.sub.4)alkylene; 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- 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 and --Ar is phenyl, thienyl, benzo[1,3]dioxolyl, cyclopentyl or cyclohexyl; and R.sup.1, R.sup.2 and R.sup.3 are each independently hydroxy, halo, trifluoromethyl, trifluoromethoxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.7)alkyl. 13. A compound as recited in claim 8 wherein A is (C.sub.1 -C.sub.6)alkanoyl, said A optionally mono-, di- or tri-substituted on carbon independently with halo; K is (C.sub.3 -C.sub.8)alkylene, said (C.sub.3 -C.sub.8)alkylene being mono-unsaturated; 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- optionally substituted with up to four substituents independently selected from fluorines 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 and --Ar is phenyl, thienyl, cyclopentyl or cyclohexyl; and R.sup.1, R.sup.2 and R.sup.3 are each independently hydroxy, halo, trifluoromethyl, trifluoromethoxy, (C.sub.1 -C.sub.4)alkoxy or (C.sub.1 -C.sub.7)alkyl. 14. A compound as recited in claim 4 wherein A is propanoyl; Q is n-hexylene; Z is carboxyl; K is methylene; and M is 4-(n-1-hydroxylhexyl)phenyl. 15. 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. 16. The method as recited in claim 15 wherein osteoporosis, osteotomy, childhood idiopathic bone loss or bone loss associated with periodontitis is treated. 17. The method as recited in claim 16 wherein osteoporosis is treated in a human. 18. The method as recited in claim 15 wherein glucocorticoid-induced osteoporosis, hyperthyroidism-induced osteoporosis, immobilization-induced osteoporosis, heparin-induced osteoporosis or immunosuppressive-induced osteoporosis is treated. 19. 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. 20. The method as recited in claim 19 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. 21. The method as recited in claim 19 wherein a bone fracture is treated in a human. 22. 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. 23. The pharmaceutical composition as recited in claim 22 for the treatment of osteoporosis wherein the therapeutically effective amount is an osteoporosis treating amount. 24. 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. 25. The pharmaceutical composition as recited in claim 24 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. 26. 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. 27. 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. 28. A pharmaceutical composition as recited in claim 27 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 hep-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-tetrahydroisoquinoline; 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. 29. A pharmaceutical composition as recited in claim 27 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. 30. 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. 31. The method as recited in claim 30 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-eth6.times.y)-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 -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. 32. The method as recited in claim 30 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. 33. 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. 34. The kit as recited in claim 33 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}-[6hydroxy-2-(4-hydroxy-phenyl)-benzo[b]thiophe n-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)-phenyll-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. 35. The kit as recited in 33 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. 36. 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. 37. The pharmaceutical composition as recited in claim 36 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. 38. 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. 39. The method as recited in claim 38 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. 40. 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. 41. The kit as recited in claim 40 wherein the anabolic agent other than the claim 1 compound is IGF-1, prostaglandin, prostaglandin agonistlantagonist, sodium fluonde, parathyroid hormone (PTH), active fragments of parathyroid hormone, growth hormone or growth hormone secretagogues or a pharmaceutically acceptable salt thereof. 42. A compound having the Formula IA ##STR29## or a pharmaceutically acceptable salt or prodrug thereof wherein B is N; A is (C.sub.1 -C.sub.6)alkanoyl, or (C.sub.3 -C.sub.7)cycloalkyl(C.sub.1 -C.sub.6)alkanoyl, said A moieties optionally mono-, di- or tri- substituted independently on carbon with hydroxy or halo; 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- 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-, --(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 phenylsulfonyocarbamoyl; K is (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 optionally 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, optionally 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 independents 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, H, 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 independently on carbon 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 cycloct-1-yl then said (C.sub.5 -C.sub.8)cycloalkyl substituents are not substituted at the one position with hydroxy and with the proviso that 6-[(3-phenyl-propyly(2-propyl-pentanoyl)-amino]-hexanoic acid and its ethyl ester are not included. 43. A pharmaceutical composition comprising: a. a therapeutically effective amount of a compound of claim 42 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. 44. 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 42 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]thiophen-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. 45. A kit comprising: a. a therapeutically effective amount of a compound of claim 42 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 pharmaceutically 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. 46. 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 42 or a pharmaceutically acceptable salt or prodrug thereof. 47. 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 42 or a pharmaceutically acceptable salt or prodrug thereof. 48. A pharmaceutical composition which comprises a therapeutically effective amount of a compound of claim 42 or a pharmaceutically acceptable salt or prodrug thereof and a pharmaceutically acceptable carrier. 49. The compound: 5-{3-[cyclopropanecarbonyl-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino] -propyl}-thiophene-2-carboxylic acid; 5-[3-(benzofuran-2-ylmethyl-cyclopropanecarbonyl-amino)-propyl]-thiophene-2 -carboxylic acid; 5-(3-{[3-(3-chloro-phenyl)-propyl]-propionyl-amino}-propyl)-thiophene-2-car boxylic acid; 5-(3-{-acetyl-[3-(3-chloro-phenyl)-propyl]-amino}-propylythiophene-2-carbo xylic acid; 5-(3-{[3-(3-chloro-phenyl)-propyo]-hydroxyacetyl-amino}-propyl)-thiophene-2 -carboxylic acid; 5-(3-{[3-(3-chloro-phenyl)-propyl]-cyclopropanecarbonyl-amino}-propyl)-thio phene-2-carboxylic acid; 5-(3-{[3-(3-chloro-phenyl)-propyl]-cyclobutanecarbonyl-amino}-propyl)-thiop hene-2-carboxylic acid; 5-(3-{butyryl-[3-(3-chloro-phenyl)-propyl]-amino}-propyl)-thiophene-2-carbo xylic acid; 5-(3-{[3-(3-chloro-phenyl)-propyl]-propionyl-amino}-propyl)-furan-2-carboxy lic acid; 5-(3-{[3-(3-chloro-phenylypropyl]-cyclopropanecarbonyl-amino}-propyl)-furan -2-carboxylic acid; or 5-(3-{acetyl-[3-(3-chloro-phenyl)propyl]-amino}-propyl)-furan-2-carboxylic acid, or a pharmaceutically acceptable salt or prodrug thereof.

Details for Patent 6,649,657

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