| 摘要 |
1. A method of treating a condition which presents with low bone mass in a mammal comprising administering to said mammal an EP4 receptor selective agonist, which is a compound of formula I: or a pharmaceutically acceptable salt of said compound, wherein Q is COOR<3> CONHR<4> or tetrazol-5-yl; A is a single or cis double bond; B is a single or trans double bond; (U is R<2> is alpha-thienyl, phenyl, phenoxy, monosubstituted phenyl and monosubstituted phenoxy, said substituents being chloro, fluoro, phenyl, methoxy, trifluoromethyl or (C1-C3)alkyl; R<3> is hydrogen, (C1-C5) alkyl, phenyl or p-biphenyl; R<4> is COR<5> or SO2R<5>; and R<5> is phenyl or (C1-C5)alkyl; or 7-(2S-(3R-hydroxy-4-phenyl-butyl)-5-oxo-pyrrolidin-1-yl)-heptanoic acid. 2. A method of claim 1 wherein Q is 5-tetrazolyl and (U is 3. A method of claim 2 wherein said compound of formula I is 5R-(3S-hydroxy-4-phenyl-but-1-enyl)-1-[6-(1H-tetrazol-5-yl)-hexyl]-pyrrolidin-2-one, 5S-(3R-hydroxy-4-phenyl-butyl)-1-[6-(1H-tetrazol-5-yl)-hexyl]-pyrrolidin-2-one, 5S-(4-(3-chloro-phenyl)-3R-hydroxy-butyl)-1-(6-(2H-tetrazol-5-yl)-hexyl-pyrrolidin-2-one or 5S-(3R-hydroxy-4-(3-trifluoromethyl-phenyl)-butyl)-1-(6-(2H-tetrazol-5-yl)-hexyl)-pyrrolidin-2-one. 4. A method of claim 1 wherein Q is COOH and (U is 5. A method of claim 4 wherein said compound is 7-(2S-(3R-hydroxy-4-phenyl-butyl)-5-oxo-pyrrolidin-1-yl)-heptanoic acid, 7-[2R-(3S-hydroxy-4-phenyl-but-1-enyl)-5-oxo-pyrrolidin-1-yl]-heptanoic acid, 7-{2S-[3R-hydroxy-4-(3-trifluoromethoxy-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-heptanoic acid, 7-{2S-[3R-hydroxy-4-(3-phenoxy-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-heptanoic acid, 7-(2S-(3R-hydroxy-4-(3-trifluoromethyl-phenyl)-butyl)-5-oxo-pyrrolidin-1-yl)-heptanoic acid or 7-{2S-[4-(3-chlorphenyl)-3R-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}-heptanoic acid. 6. A method of any of claims 1-5 wherein said condition is osteoporosis, frailty, an osteoporotic fracture, a bone defect, childhood idiopathic bone loss, alveolar bone loss, mandibular bone loss, bone fracture, osteotomy, bone loss associated with periodontitis, or prosthetic ingrowth. 7. A method of claim 2 wherein said composition is administered systemically or locally. 8. A method selected from 7-{2S-[3R-hydroxy-4-(3-phenoxy-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl)-heptanoic acid; 7-(2-(3R-hydroxy-4-(3-trifluoromethyl-phenyl)-butyl)-5-oxo-pyrrolidin-1-yl)-heptanoic acid; 7-{2S-[4-(3-chloro-phenyl)-3R-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}-heptanoic acid; 5S-[4-(3-chloro-phenyl)-3R-hydroxy-butyl]-1-[6-(2H-tetrazol-5-yl)-hexyl]-pyrrolidin-2-one; and 5S-(3R-hydroxy-4-(3-trifluoromethyl-phenyl)-butyl)-1-(6-(2H-tetrazol-5-yl)-hexyl)-pyrrolidin-2-one. 9. A pharmaceutical composition comprising a compound of claim 8 and a pharmaceutically acceptable diluent or carrier. 10. Use a compound of claim 8 as a medicine.
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