Claims
- 1. 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 the formula IA a prodrug thereof or a pharmaceutically acceptable salt of said compound or said prodrug whereinA is hydrogen or hydroxy; B is propylene, propenylene or propynylene; Q is propylene, —CH2OCH2—, thiazolyl, pyridyl, phenyl or thienyl; Z is carboxyl, (C1-C6)alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl or 5-oxo-1,2,4-oxadiazolyl; K is ethylene or ethynylene; L is a bond or —CO—; M is —Ar, —Ar1—V—Ar2, —Ar1—S—Ar2 or —Ar1—O—Ar2 wherein Ar, Ar1 and Ar2 are each independently a fully saturated, partially unsaturated 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 and/or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, or, a tricyclic ring consisting of three fused partially saturated, fully saturated or fully unsaturated five and/or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, any of said partially saturated or fully saturated rings optionally having one or more oxo groups substituted on carbon, said Ar, Ar1 and Ar2 moieties are each independently optionally substituted, on one ring if the moiety is monocyclic, on one or both rings if the moiety is bicyclic, or on one, two or three rings is the moiety is tricyclic, on carbon with up to three substituents independently selected from R1, R2 and R3 wherein R1, R2 and R3 are hydroxy, nitro, halo, (C1-C7)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (C2-C7)alkenyl, (C2-C7)alkynyl, (C3-C7)cycloalkyl, (C3-C7),cycloalkyl(C1-C4)alkyl, (C3-C7)cycloalkyl(C1-C4)alkanoyl, formyl, (C1-C8)alkanoyl, (C1-C6)alkanoyl(C1-C6)alkyl, aminocarbonylamino or mono-N-, di-N,N-, di-N,N′- or tri-N,N,N′—(C1-C4)alkyl substituted aminocarbonylamino, (C1-C4)alkanoylamino, (C1-C4)alkoxycarbonylamino, sulfonamido, hydroxysulfonyl, (C1-C4)alkylsulfonamido, amino, mono-N- or di-N,N—(C1-C4)alkylamino, carbamoyl, mono-N- or di-N,N—(C1-C4)alkylcarbamoyl, cyano, thiol, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C4)alkylsulfonyl or mono-N- or di-N,N—(C1-C4)alkylaminosulfinyl; R1, R2 and R3, when containing an alkyl, alkenyl, alkylene or alkenylene moiety, are optionally straight or branched and are optionally mono-, di- or tri-substituted on carbon independently with halo or hydroxy; and V is a bond, —CO— or (C1-C3)alkylene optionally mono- or di-substituted independently with hydroxy or fluoro, provided that (1) when L is —CO—, A is hydroxy; and (2) when L is a bond and M is phenyl, said phenyl is substituted with one to three substituents selected from R1, R2 and R3.
- 2. The method as recited in claim 1 wherein osteoporosis, osteotomy, childhood idiopathic bone loss or bone loss associated with periodontitis is treated.
- 3. The method as recited in claim 2 wherein osteoporosis is treated in a human.
- 4. The method as recited in claim 3 wherein glucocorticoid-induced osteoporosis, hyperthyroidism-induced osteoporosis, immobilization-induced osteoporosis, heparin-induced osteoporosis or immunosuppressive-induced osteoporosis is treated.
- 5. A method for augmenting and maintaining bone mass in a mammal comprising administering to a mammal a therapeutically effective amount of a compound of the formula IA a prodrug thereof or a pharmaceutically acceptable salt of said compound or said prodrug whereinA is hydrogen or hydroxy; B is propylene, propenylene or propynylene; Q is propylene, —CH2OCH2—, thiazolyl, pyridyl, phenyl or thienyl; Z is carboxyl, (C1-C6)alkoxycarbonyl, tetrazolyl, 1,2,4-oxadiazolyl or 5-oxo-1,2,4-oxadiazolyl; K is ethylene or ethenylene; L is a bond or —CO—; M is —Ar, —Ar1—V—Ar2, —Ar1—S—Ar2 or —Ar1—O—Ar2 wherein Ar, Ar1 and Ar2 are each independently a fully saturated, partially unsaturated 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 and/or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, or, a tricyclic ring consisting of three fused partially saturated, fully saturated or fully unsaturated five and/or six membered rings, taken independently, optionally having one to four heteroatoms selected independently from nitrogen, sulfur and oxygen, any of said partially saturated or fully saturated rings optionally having one or more oxo groups substituted on carbon, said Ar, Ar1 and Ar2 moieties are each independently optionally substituted, on one ring if the moiety is monocyclic, on one or both rings if the moiety is bicyclic, or on one, two or three rings is the moiety is tricyclic, on carbon with up to three substituents independently selected from R1, R2 and R3 wherein R1, R2 and R3 are hydroxy, nitro, halo, (C1-C7)alkoxy, (C1-C4)alkoxy(C1-C4)alkyl, (C1-C4)alkoxycarbonyl, (C1-C7)alkyl, (C2-C7)alkenyl, (C2-C7)alkyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C4)alkyl, (C3-C7)cycloalkyl(C1-C4)alkanoyl, formyl, (C1-C8)alkanoyl, (C1-C6)alkanoyl(C1-C6)alkyl, aminocarbonylamino or mono-N-, di-N,N-, di-N,N′- or tri-N,N,N′—(C1-C4)alkyl substituted aminocarbonylamino, (C1-C4)alkanoylamino, (C1-C4)alkoxycarbonylamino, sulfonamido, hydroxysulfonyl, (C1-C4)alkylsulfonamido, amino, mono-N- or di-N,N—(C1-C4)alkylamino, carbamoyl, mono-N- or di-N,N—(C1-C4)alkylcarbamoyl, cyano, thiol, (C1-C6)alkylthio, (C1-C6)alkylsulfinyl, (C1-C4)alkylsulfonyl or mono-N- or di-N,N—(C1-C4)alkylaminosulfinyl; R1, R2 and R3, when containing an alkyl, alkenyl, alkylene or alkenylene moiety, are optionally straight or branched and are optionally mono-, di- or tri-substituted on carbon independently with halo or hydroxy; and V is a bond, —CO— or (C1-C3)alkylene optionally mono- or di-substituted independently with hydroxy or fluoro; provided that (1) when L is —CO—, A is hydroxy; and (2) when L is a bond and M is phenyl, said phenyl is substituted with one to three substituents selected from R1, R2 and R3.
- 6. The method as recited in claim 5 wherein bone heating 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.
- 7. The method as recited in claim 5 wherein a bone fracture is treated in a human.
Parent Case Info
This application is the national stage of copending International Patent Application Number PCT/IB98/00866, filed Jun. 4, 1998, which is a continuation of U.S. Provisional Application No. 60/050,575, filed Jun. 23, 1997.
PCT Information
Filing Document |
Filing Date |
Country |
Kind |
PCT/IB98/00866 |
|
WO |
00 |
Publishing Document |
Publishing Date |
Country |
Kind |
WO98/58911 |
12/30/1998 |
WO |
A |
US Referenced Citations (5)
Foreign Referenced Citations (4)
Number |
Date |
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2434133 |
Jan 1976 |
DE |
2548955 |
Oct 1975 |
DK |
1521688 |
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GB |
WO9731640 |
Sep 1997 |
WO |
Non-Patent Literature Citations (1)
Entry |
King FD. Medicinal Chemistry: Principles and Practice. Pub;osjed by The Royal Society of Chemistry. pp. 206-209, 1994. |
Provisional Applications (1)
|
Number |
Date |
Country |
|
60/050575 |
Jun 1997 |
US |