SK5562003A3 - EP4 receptor selective agonists in the treatment of osteoporosis - Google Patents

EP4 receptor selective agonists in the treatment of osteoporosis Download PDF

Info

Publication number: SK5562003A3
Authority: SK; Slovakia
Prior art keywords: prodrugs; compounds; alkyl; bone; phenyl
Prior art date: 2000-11-27

Application number

SK556-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Kimberly O'keefe Cameron

Bruce Allen Lefker

Original Assignee

Pfizer Prod Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-11-27

Filing date

2001-11-05

Publication date

2004-08-03

2001-11-05 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2004-08-03 Publication of SK5562003A3 publication Critical patent/SK5562003A3/sk

Links

208000001132 Osteoporosis Diseases 0.000 title claims abstract description 45
238000011282 treatment Methods 0.000 title claims description 24
239000000556 agonist Substances 0.000 title abstract description 43
101150109738 Ptger4 gene Proteins 0.000 title abstract description 10
150000001875 compounds Chemical class 0.000 claims abstract description 246
210000000988 bone and bone Anatomy 0.000 claims abstract description 135
208000010392 Bone Fractures Diseases 0.000 claims abstract description 50
241000124008 Mammalia Species 0.000 claims abstract description 21
206010065687 Bone loss Diseases 0.000 claims abstract description 20
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
230000007547 defect Effects 0.000 claims abstract description 6
208000002679 Alveolar Bone Loss Diseases 0.000 claims abstract description 5
208000001164 Osteoporotic Fractures Diseases 0.000 claims abstract description 4
201000001245 periodontitis Diseases 0.000 claims abstract description 4
-1 (C 2 -C 7) -alkenyl Chemical group 0.000 claims description 174
239000000651 prodrug Substances 0.000 claims description 147
229940002612 prodrug Drugs 0.000 claims description 147
150000003839 salts Chemical class 0.000 claims description 107
239000000203 mixture Substances 0.000 claims description 87
229910052757 nitrogen Chemical group 0.000 claims description 45
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 40
125000000217 alkyl group Chemical group 0.000 claims description 36
QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 claims description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 26
229920006395 saturated elastomer Polymers 0.000 claims description 24
229910052799 carbon Inorganic materials 0.000 claims description 20
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 19
125000001153 fluoro group Chemical group F* 0.000 claims description 19
125000003545 alkoxy group Chemical group 0.000 claims description 16
125000001424 substituent group Chemical group 0.000 claims description 16
125000004093 cyano group Chemical group *C#N 0.000 claims description 14
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 12
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
239000001301 oxygen Substances 0.000 claims description 11
239000011593 sulfur Chemical group 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 11
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 9
125000001589 carboacyl group Chemical group 0.000 claims description 9
125000004043 oxo group Chemical group O=* 0.000 claims description 9
125000001544 thienyl group Chemical group 0.000 claims description 9
125000002619 bicyclic group Chemical group 0.000 claims description 8
239000000460 chlorine Substances 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
150000002367 halogens Chemical group 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 6
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 6
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
125000005236 alkanoylamino group Chemical group 0.000 claims description 5
125000006598 aminocarbonylamino group Chemical group 0.000 claims description 5
229910052801 chlorine Inorganic materials 0.000 claims description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 4
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
239000011737 fluorine Substances 0.000 claims description 4
229910052731 fluorine Inorganic materials 0.000 claims description 4
230000000366 juvenile effect Effects 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000002950 monocyclic group Chemical group 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
125000005843 halogen group Chemical group 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
125000000335 thiazolyl group Chemical group 0.000 claims description 3
125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000001624 naphthyl group Chemical group 0.000 claims description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
125000003831 tetrazolyl group Chemical group 0.000 claims description 2
125000003396 thiol group Chemical class [H]S* 0.000 claims 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims 1
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
238000000034 method Methods 0.000 abstract description 124
150000003180 prostaglandins Chemical class 0.000 abstract description 24
208000036119 Frailty Diseases 0.000 abstract 1
206010003549 asthenia Diseases 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 527
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 333
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 327
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 199
235000019439 ethyl acetate Nutrition 0.000 description 188
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 130
238000005481 NMR spectroscopy Methods 0.000 description 104
239000000243 solution Substances 0.000 description 101
238000004587 chromatography analysis Methods 0.000 description 98
239000002609 medium Substances 0.000 description 91
238000000746 purification Methods 0.000 description 85
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 75
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
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OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 54
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206010017076 Fracture Diseases 0.000 description 47
230000002829 reductive effect Effects 0.000 description 47
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
239000002904 solvent Substances 0.000 description 41
MNWFXJYAOYHMED-UHFFFAOYSA-N hexane carboxylic acid Natural products CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 39
238000002360 preparation method Methods 0.000 description 39
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
229940011871 estrogen Drugs 0.000 description 34
239000000262 estrogen Substances 0.000 description 34
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
239000012442 inert solvent Substances 0.000 description 32
150000001450 anions Chemical class 0.000 description 31
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
239000002253 acid Substances 0.000 description 30
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
229910000104 sodium hydride Inorganic materials 0.000 description 26
239000005557 antagonist Substances 0.000 description 25
239000012279 sodium borohydride Substances 0.000 description 25
229910000033 sodium borohydride Inorganic materials 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
230000000694 effects Effects 0.000 description 23
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239000003921 oil Substances 0.000 description 23
235000019198 oils Nutrition 0.000 description 23
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 21
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241000700159 Rattus Species 0.000 description 19
239000003795 chemical substances by application Substances 0.000 description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
230000011164 ossification Effects 0.000 description 18
238000010992 reflux Methods 0.000 description 17
VMKAFJQFKBASMU-QGZVFWFLSA-N (r)-2-methyl-cbs-oxazaborolidine Chemical compound C([C@@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-QGZVFWFLSA-N 0.000 description 16
239000012267 brine Substances 0.000 description 16
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 16
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
210000001519 tissue Anatomy 0.000 description 16
241000251539 Vertebrata <Metazoa> Species 0.000 description 15
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
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235000019341 magnesium sulphate Nutrition 0.000 description 15
206010020649 Hyperkeratosis Diseases 0.000 description 14
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
239000003054 catalyst Substances 0.000 description 14
TVQGDYNRXLTQAP-UHFFFAOYSA-N ethyl heptanoate Chemical compound CCCCCCC(=O)OCC TVQGDYNRXLTQAP-UHFFFAOYSA-N 0.000 description 14
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NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 14
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TYGXITCKYVKKFC-SNVBAGLBSA-N methyl 5-[3-[(2r)-2-formyl-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=O TYGXITCKYVKKFC-SNVBAGLBSA-N 0.000 description 11
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BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 9
239000003039 volatile agent Substances 0.000 description 9
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229910052500 inorganic mineral Inorganic materials 0.000 description 8
AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 8
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230000018109 developmental process Effects 0.000 description 1
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IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
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XQRLCLUYWUNEEH-UHFFFAOYSA-N diphosphonic acid Chemical compound OP(=O)OP(O)=O XQRLCLUYWUNEEH-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
SKUHWSDHMJMHIW-UHFFFAOYSA-L disodium;[(4-chlorophenyl)sulfanyl-[hydroxy(oxido)phosphoryl]methyl]-hydroxyphosphinate Chemical group [Na+].[Na+].OP([O-])(=O)C(P(O)([O-])=O)SC1=CC=C(Cl)C=C1 SKUHWSDHMJMHIW-UHFFFAOYSA-L 0.000 description 1
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239000006185 dispersion Substances 0.000 description 1
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JGMOKGBVKVMRFX-HQZYFCCVSA-N dydrogesterone Chemical compound C1=CC2=CC(=O)CC[C@@]2(C)[C@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 JGMOKGBVKVMRFX-HQZYFCCVSA-N 0.000 description 1
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238000004520 electroporation Methods 0.000 description 1
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230000002255 enzymatic effect Effects 0.000 description 1
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235000004626 essential fatty acids Nutrition 0.000 description 1
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PROQIPRRNZUXQM-ZXXIGWHRSA-N estriol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H]([C@H](O)C4)O)[C@@H]4[C@@H]3CCC2=C1 PROQIPRRNZUXQM-ZXXIGWHRSA-N 0.000 description 1
239000000328 estrogen antagonist Substances 0.000 description 1
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229960003399 estrone Drugs 0.000 description 1
VUCAHVBMSFIGAI-ZFINNJDLSA-M estrone sodium sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 VUCAHVBMSFIGAI-ZFINNJDLSA-M 0.000 description 1
229960002568 ethinylestradiol Drugs 0.000 description 1
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XHFUVBWCMLLKOZ-UHFFFAOYSA-N ethyl 2-amino-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(N)=N1 XHFUVBWCMLLKOZ-UHFFFAOYSA-N 0.000 description 1
KTYIFXLNIMPSKI-UHFFFAOYSA-N ethyl 2-bromo-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(Br)S1 KTYIFXLNIMPSKI-UHFFFAOYSA-N 0.000 description 1
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FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
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238000004108 freeze drying Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
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GCCIFDUTISMRTG-TUPTUZDRSA-N haloprogesterone Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@](C(=O)C)(Br)[C@@]2(C)CC1 GCCIFDUTISMRTG-TUPTUZDRSA-N 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
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SDAXRHHPNYTELL-UHFFFAOYSA-N heptanenitrile Chemical compound CCCCCCC#N SDAXRHHPNYTELL-UHFFFAOYSA-N 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
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238000009396 hybridization Methods 0.000 description 1
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150000002430 hydrocarbons Chemical class 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
229910000043 hydrogen iodide Inorganic materials 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 1
229950000801 hydroxyprogesterone caproate Drugs 0.000 description 1
150000004806 hydroxypyridines Chemical class 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000005462 in vivo assay Methods 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
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210000003734 kidney Anatomy 0.000 description 1
210000003292 kidney cell Anatomy 0.000 description 1
239000008101 lactose Substances 0.000 description 1
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229960004400 levonorgestrel Drugs 0.000 description 1
XZEUAXYWNKYKPL-WDYNHAJCSA-N levormeloxifene Chemical compound C1([C@H]2[C@@H](C3=CC=C(C=C3OC2(C)C)OC)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 XZEUAXYWNKYKPL-WDYNHAJCSA-N 0.000 description 1
229950002728 levormeloxifene Drugs 0.000 description 1
229940002661 lipitor Drugs 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
210000004698 lymphocyte Anatomy 0.000 description 1
229960001910 lynestrenol Drugs 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
BQNQIHYLDYHYQP-UHFFFAOYSA-M magnesium;1-chloro-3-methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC(Cl)=C1 BQNQIHYLDYHYQP-UHFFFAOYSA-M 0.000 description 1
KZGFEBLGGYOPML-UHFFFAOYSA-M magnesium;1-fluoro-3-methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC(F)=C1 KZGFEBLGGYOPML-UHFFFAOYSA-M 0.000 description 1
JHMNJUQVLPODJN-UHFFFAOYSA-M magnesium;1-fluoro-4-methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=C(F)C=C1 JHMNJUQVLPODJN-UHFFFAOYSA-M 0.000 description 1
SCEZYJKGDJPHQO-UHFFFAOYSA-M magnesium;methanidylbenzene;chloride Chemical compound [Mg+2].[Cl-].[CH2-]C1=CC=CC=C1 SCEZYJKGDJPHQO-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000003550 marker Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
HCFSGRMEEXUOSS-JXEXPEPMSA-N medrogestone Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(C)[C@@]1(C)CC2 HCFSGRMEEXUOSS-JXEXPEPMSA-N 0.000 description 1
229960000606 medrogestone Drugs 0.000 description 1
MBKDYNNUVRNNRF-UHFFFAOYSA-N medronic acid Chemical compound OP(O)(=O)CP(O)(O)=O MBKDYNNUVRNNRF-UHFFFAOYSA-N 0.000 description 1
229960003846 melengestrol acetate Drugs 0.000 description 1
230000009245 menopause Effects 0.000 description 1
230000005906 menstruation Effects 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
ULSSGHADTSRELG-UHFFFAOYSA-N methyl 2-(3-bromophenyl)acetate Chemical compound COC(=O)CC1=CC=CC(Br)=C1 ULSSGHADTSRELG-UHFFFAOYSA-N 0.000 description 1
HTBBVKFFDDQVER-UHFFFAOYSA-N methyl 2-(3-chlorophenyl)acetate Chemical compound COC(=O)CC1=CC=CC(Cl)=C1 HTBBVKFFDDQVER-UHFFFAOYSA-N 0.000 description 1
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
SSBHXDDGZAQNCH-HMTLIYDFSA-N methyl 4-[3-[(2r)-2-[4-(1,3-benzodioxol-5-yl)-3-hydroxybut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(O)CC1=CC=C(OCO2)C2=C1 SSBHXDDGZAQNCH-HMTLIYDFSA-N 0.000 description 1
GENAXNGYOZJZJY-NRFANRHFSA-N methyl 4-[3-[(2r)-2-[4-(1,3-benzodioxol-5-yl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=C(OCO2)C2=C1 GENAXNGYOZJZJY-NRFANRHFSA-N 0.000 description 1
BPHNMVWUWRHHOZ-CQSZACIVSA-N methyl 4-[3-[(2r)-2-formyl-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=O BPHNMVWUWRHHOZ-CQSZACIVSA-N 0.000 description 1
PRRBXZOTQDDOFR-UHFFFAOYSA-N methyl 4-[3-[2-(3-hydroxy-4-phenylbutyl)-5-oxopyrrolidin-1-yl]propyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCCN1C(=O)CCC1CCC(O)CC1=CC=CC=C1 PRRBXZOTQDDOFR-UHFFFAOYSA-N 0.000 description 1
DYUWQWMXZHDZOR-UHFFFAOYSA-N methyl 4-iodobenzoate Chemical compound COC(=O)C1=CC=C(I)C=C1 DYUWQWMXZHDZOR-UHFFFAOYSA-N 0.000 description 1
MGBXTCJYKMJGCS-SNVBAGLBSA-N methyl 5-[3-[(2r)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1CO MGBXTCJYKMJGCS-SNVBAGLBSA-N 0.000 description 1
LBISABYSBNAOHO-SFHVURJKSA-N methyl 5-[3-[(2r)-2-[4-(3-chlorophenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC(Cl)=C1 LBISABYSBNAOHO-SFHVURJKSA-N 0.000 description 1
IPZKLECZSIHAFM-SFHVURJKSA-N methyl 5-[3-[(2r)-2-[4-(3-fluorophenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC(F)=C1 IPZKLECZSIHAFM-SFHVURJKSA-N 0.000 description 1
ICXPKOBEJSYAMN-SFHVURJKSA-N methyl 5-[3-[(2r)-2-[4-(4-chlorophenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=C(Cl)C=C1 ICXPKOBEJSYAMN-SFHVURJKSA-N 0.000 description 1
VUJBVOPPOJVVTG-SFHVURJKSA-N methyl 5-[3-[(2r)-2-[4-(4-fluoro-3-methylphenyl)-3-oxobut-1-enyl]-5-oxopyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=C(F)C(C)=C1 VUJBVOPPOJVVTG-SFHVURJKSA-N 0.000 description 1
ZEMUOVVDZVEIKH-SFHVURJKSA-N methyl 5-[3-[(5r)-2-oxo-5-(3-oxo-4-phenylbut-1-enyl)pyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC=C1 ZEMUOVVDZVEIKH-SFHVURJKSA-N 0.000 description 1
MGWIFQZFPLGPJQ-KRWDZBQOSA-N methyl 5-[3-[(5r)-2-oxo-5-[3-oxo-4-[2-(trifluoromethyl)phenyl]but-1-enyl]pyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC=C1C(F)(F)F MGWIFQZFPLGPJQ-KRWDZBQOSA-N 0.000 description 1
AWJFNOGSZPVOFP-SFHVURJKSA-N methyl 5-[3-[(5r)-2-oxo-5-[3-oxo-4-[3-(trifluoromethyl)phenyl]but-1-enyl]pyrrolidin-1-yl]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN1C(=O)CC[C@@H]1C=CC(=O)CC1=CC=CC(C(F)(F)F)=C1 AWJFNOGSZPVOFP-SFHVURJKSA-N 0.000 description 1
QLWUHAQCKDHUNL-UHFFFAOYSA-N methyl 5-bromothiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(Br)S1 QLWUHAQCKDHUNL-UHFFFAOYSA-N 0.000 description 1
GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
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238000002156 mixing Methods 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
UHAAFJWANJYDIS-UHFFFAOYSA-N n,n'-diethylmethanediimine Chemical compound CCN=C=NCC UHAAFJWANJYDIS-UHFFFAOYSA-N 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
PUUSSSIBPPTKTP-UHFFFAOYSA-N neridronic acid Chemical compound NCCCCCC(O)(P(O)(O)=O)P(O)(O)=O PUUSSSIBPPTKTP-UHFFFAOYSA-N 0.000 description 1
229940053934 norethindrone Drugs 0.000 description 1
VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
229960001858 norethynodrel Drugs 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
238000009806 oophorectomy Methods 0.000 description 1
238000011474 orchiectomy Methods 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
XZEUAXYWNKYKPL-URLMMPGGSA-N ormeloxifene Chemical compound C1([C@@H]2[C@H](C3=CC=C(C=C3OC2(C)C)OC)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 XZEUAXYWNKYKPL-URLMMPGGSA-N 0.000 description 1
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210000000963 osteoblast Anatomy 0.000 description 1
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150000002924 oxiranes Chemical class 0.000 description 1
238000002638 palliative care Methods 0.000 description 1
WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
229960003978 pamidronic acid Drugs 0.000 description 1
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A—HUMAN NECESSITIES
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- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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Organic Chemistry (AREA)
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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
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Animal Behavior & Ethology (AREA)
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General Chemical & Material Sciences (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Orthopedic Medicine & Surgery (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyrrole Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK556-2003A 2000-11-27 2001-11-05 EP4 receptor selective agonists in the treatment of osteoporosis SK5562003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US25327500P	2000-11-27	2000-11-27
PCT/IB2001/002073 WO2002042268A2 (en)	2000-11-27	2001-11-05	Ep4 receptor selective agonists in the treatment of osteoporosis

Publications (1)

Publication Number	Publication Date
SK5562003A3 true SK5562003A3 (en)	2004-08-03

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SK556-2003A SK5562003A3 (en)	2000-11-27	2001-11-05	EP4 receptor selective agonists in the treatment of osteoporosis

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US (3)	US6552067B2 (cs)
EP (1)	EP1339678B1 (cs)
JP (2)	JP3984164B2 (cs)
KR (1)	KR20030053063A (cs)
CN (1)	CN1476429A (cs)
AR (1)	AR035074A1 (cs)
AT (1)	ATE374182T1 (cs)
AU (1)	AU2002210848A1 (cs)
BG (1)	BG107697A (cs)
BR (1)	BR0115687A (cs)
CA (1)	CA2429850C (cs)
CY (1)	CY1106976T1 (cs)
CZ (1)	CZ20031257A3 (cs)
DE (1)	DE60130675T2 (cs)
DK (1)	DK1339678T3 (cs)
EA (1)	EA200300379A1 (cs)
EC (1)	ECSP034623A (cs)
EE (1)	EE200300246A (cs)
ES (1)	ES2291361T3 (cs)
GT (2)	GT200100238A (cs)
HN (1)	HN2001000266A (cs)
HU (1)	HUP0400807A2 (cs)
IL (1)	IL155368A0 (cs)
IS (1)	IS6775A (cs)
MA (1)	MA26961A1 (cs)
MX (1)	MXPA03004623A (cs)
NO (1)	NO20032360L (cs)
NZ (1)	NZ525164A (cs)
OA (1)	OA12533A (cs)
PA (1)	PA8533901A1 (cs)
PE (1)	PE20020637A1 (cs)
PL (1)	PL362030A1 (cs)
PT (1)	PT1339678E (cs)
SI (1)	SI1339678T1 (cs)
SK (1)	SK5562003A3 (cs)
SV (1)	SV2003000746A (cs)
TN (1)	TNSN01166A1 (cs)
TW (1)	TW200424170A (cs)
UY (1)	UY27038A1 (cs)
WO (1)	WO2002042268A2 (cs)
ZA (1)	ZA200302803B (cs)

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RU2296122C2 (ru) *	2001-07-16	2007-03-27	Ф.Хоффманн-Ля Рош Аг	Производные 2-пирролидона в качестве простаноидных агонистов и фармацевтическая композиция
NZ530885A (en)	2001-07-23	2007-09-28	Ono Pharmaceutical Co	Remedies for diseases with bone mass loss having EP4 agonist as the active ingredient
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AU2003211574A1 (en)	2002-03-05	2003-09-16	Ono Pharmaceutical Co., Ltd.	8-azaprostaglandin derivative compounds and drugs containing the compounds as the active ingredient
CA2478653A1 (en) *	2002-03-18	2003-09-25	Pfizer Products Inc.	Methods of treatment with selective ep4 receptor agonists
BR0308493A (pt) *	2002-03-18	2005-01-11	Pfizer Prod Inc	Uso de agonistas de receptor seletivo de ep4 para o tratamento da insuficiência hepática, perda de permeabilidade do canal arterial, glaucoma ou hipertensão ocular
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JP2005534653A (ja) *	2002-06-06	2005-11-17	メルクフロストカナダアンドカンパニー	眼及び骨疾患の治療に於いてｅｐ４受容体作動薬として使用するための１，５−二置換イミダゾリジン−２−オン誘導体
DE60334905D1 (de) *	2002-06-06	2010-12-23	Merck Frosst Canada Ltd	1,5-disubstituierte pyrrolid-2-on-derivate zur verwendung als ep4 rezeptor agonisten zur behandlung von augenkrankheiten wie z.b. glaukom
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GB0219143D0 (en) *	2002-08-16	2002-09-25	Univ Leicester	Modified tailed oligonucleotides
ES2584606T3 (es)	2002-10-10	2016-09-28	Ono Pharmaceutical Co., Ltd.	Microesferas que comprenden ONO-1301
AU2003275838A1 (en) *	2002-10-25	2004-05-13	Beunard, Jean-Luc	Pyrrolidin-2-on derivatives as ep4 receptor agonists
CA2505127A1 (en)	2002-11-08	2004-05-27	James B. Doherty	Ophthalmic compositions for treating ocular hypertension
US7196082B2 (en)	2002-11-08	2007-03-27	Merck & Co. Inc.	Ophthalmic compositions for treating ocular hypertension
US7053085B2 (en)	2003-03-26	2006-05-30	Merck & Co. Inc.	EP4 receptor agonist, compositions and methods thereof
RU2311409C2 (ru) *	2003-01-10	2007-11-27	Ф.Хоффманн-Ля Рош Аг	Производные 2-пиперидона в качестве агонистов простагландина
US7256211B1 (en) *	2003-01-21	2007-08-14	Ono Pharmaceutical Co., Ltd.	8-azaprostaglandin derivatives and medical use thereof
ATE394372T1 (de)	2003-03-03	2008-05-15	Serono Lab	G-lactamderivate als prostaglandinagonisten
US6734201B1 (en)	2003-06-02	2004-05-11	Allergan, Inc.	8-Azaprostaglandin carbonate and thiocarbonate analogs as therapeutic agents
US6734206B1 (en)	2003-06-02	2004-05-11	Allergan, Inc.	3-oxa-8-azaprostaglandin analogs as agents for lowering intraocular pressure
JP2006528154A (ja)	2003-07-18	2006-12-14	アプライドリサーチシステムズエーアールエスホールディングナームロゼフェンノートシャップ	プロスタグランジン受容体のモジュレータとしてのヒドラジド誘導体
US7034051B2 (en) *	2003-08-28	2006-04-25	Adolor Corporation	Fused bicyclic carboxamide derivatives and methods of their use
CN1845914A (zh)	2003-09-02	2006-10-11	默克公司	用于治疗眼压过高的眼用组合物
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BR0115687A (pt)	2003-09-09
CY1106976T1 (el)	2012-09-26
WO2002042268A3 (en)	2002-07-25
OA12533A (en)	2006-06-05
ATE374182T1 (de)	2007-10-15
SV2003000746A (es)	2003-01-13
MXPA03004623A (es)	2003-09-05
DK1339678T3 (da)	2008-02-04
KR20030053063A (ko)	2003-06-27
GT200100238A (es)	2002-06-26
UY27038A1 (es)	2002-07-31
EA200300379A1 (ru)	2003-08-28
NZ525164A (en)	2005-04-29
MA26961A1 (fr)	2004-12-20
AU2002210848A1 (en)	2002-06-03
US6747054B2 (en)	2004-06-08
DE60130675T2 (de)	2008-01-24
US7192979B2 (en)	2007-03-20
TNSN01166A1 (fr)	2005-11-10
WO2002042268A2 (en)	2002-05-30
GT200100238AA (es)	2004-05-12
HN2001000266A (es)	2002-01-30
DE60130675D1 (de)	2007-11-08
HUP0400807A2 (hu)	2004-07-28
EP1339678B1 (en)	2007-09-26
US20020065308A1 (en)	2002-05-30
AR035074A1 (es)	2004-04-14
IL155368A0 (en)	2003-11-23
PT1339678E (pt)	2007-11-30
NO20032360D0 (no)	2003-05-26
CZ20031257A3 (cs)	2004-04-14
ECSP034623A (es)	2003-07-25
ES2291361T3 (es)	2008-03-01
IS6775A (is)	2003-04-10
US20030149086A1 (en)	2003-08-07
SI1339678T1 (sl)	2007-12-31
JP2007197467A (ja)	2007-08-09
JP3984164B2 (ja)	2007-10-03
TW200424170A (en)	2004-11-16
US6552067B2 (en)	2003-04-22
NO20032360L (no)	2003-07-23
JP2004521869A (ja)	2004-07-22
CA2429850C (en)	2008-12-30
ZA200302803B (en)	2004-04-13
PA8533901A1 (es)	2002-11-28
PE20020637A1 (es)	2002-07-18
PL362030A1 (en)	2004-10-18
US20040259921A1 (en)	2004-12-23
BG107697A (en)	2004-01-30
CN1476429A (zh)	2004-02-18
CA2429850A1 (en)	2002-05-30
EE200300246A (et)	2003-10-15
EP1339678A2 (en)	2003-09-03

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Publication	Publication Date	Title
SK5562003A3 (en)	2004-08-03	EP4 receptor selective agonists in the treatment of osteoporosis
US6642266B2 (en)	2003-11-04	EP4 receptor selective agonists in the treatment of osteoporosis
DE69736007T2 (de)	2006-12-28	Vorbeugung des verlustes und wiederherstellung von knochenmasse unter verwendung von prostaglandin-analogen
JPH11180926A (ja)	1999-07-06	骨粗しょう症用化合物
US20030008895A1 (en)	2003-01-09	Prostaglandin agonists
HK1059433A (en)	2004-07-02	Ep4 receptor selective agonists in the treatment of osteoporosis
HK1051366A (en)	2003-08-01	Ep4 receptor selective agonists in the treatment of osteoporosis