JP4550417B2 - プロスタグランジンｅｐ２及び／又はｅｐ４受容体のリガンドとしてのポリアゾリジノン化合物 - Google Patents
プロスタグランジンｅｐ２及び／又はｅｐ４受容体のリガンドとしてのポリアゾリジノン化合物 Download PDFInfo
- Publication number
- JP4550417B2 JP4550417B2 JP2003537631A JP2003537631A JP4550417B2 JP 4550417 B2 JP4550417 B2 JP 4550417B2 JP 2003537631 A JP2003537631 A JP 2003537631A JP 2003537631 A JP2003537631 A JP 2003537631A JP 4550417 B2 JP4550417 B2 JP 4550417B2
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- JP
- Japan
- Prior art keywords
- ethyl
- benzoic acid
- group
- oxopyrazolidine
- solution
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 227
- 150000003180 prostaglandins Chemical class 0.000 title abstract description 16
- 101150109738 Ptger4 gene Proteins 0.000 title abstract description 14
- 239000003446 ligand Substances 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- -1 3- (hydroxyoctyl) -5-oxopyrazolidine-1-yl Chemical group 0.000 claims description 69
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- 239000005711 Benzoic acid Substances 0.000 claims description 30
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 29
- 235000010233 benzoic acid Nutrition 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 27
- 201000010099 disease Diseases 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000002837 carbocyclic group Chemical group 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 9
- XZWDACYVXIULCX-UHFFFAOYSA-N 4-[2-[2-(4-hydroxynonyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCCC(O)CCCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 XZWDACYVXIULCX-UHFFFAOYSA-N 0.000 claims description 8
- KEQOYEUKTHDSDS-ALCCZGGFSA-N 4-[2-[2-[(z)-4-hydroxynon-2-enyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCCC(O)\C=C/CN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 KEQOYEUKTHDSDS-ALCCZGGFSA-N 0.000 claims description 8
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 8
- 230000035558 fertility Effects 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- FXEVKFYZRMILMZ-UHFFFAOYSA-N 4-[2-[2-(3-hydroxy-5-methylhexyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CC(C)CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 FXEVKFYZRMILMZ-UHFFFAOYSA-N 0.000 claims description 7
- LBGUNFMRRVJPSG-UHFFFAOYSA-N 4-[2-[2-(4-hydroxy-4-methylheptyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCC(C)(O)CCCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 LBGUNFMRRVJPSG-UHFFFAOYSA-N 0.000 claims description 7
- NTVVAIFSHLCKGX-UHFFFAOYSA-N 4-[2-[2-(4-hydroxynon-2-ynyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCCC(O)C#CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 NTVVAIFSHLCKGX-UHFFFAOYSA-N 0.000 claims description 7
- MGCQBMZFRDABAR-UHFFFAOYSA-N 4-[2-[2-[4-(1-ethylcyclobutyl)-4-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C1CC(=O)N(CCC=2C=CC(=CC=2)C(O)=O)N1CCCC(O)C1(CC)CCC1 MGCQBMZFRDABAR-UHFFFAOYSA-N 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- SIGCFCMKKRESGW-UHFFFAOYSA-N 4-[2-[2-(3-cyclobutyl-3-hydroxypropyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C1CCC1C(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 SIGCFCMKKRESGW-UHFFFAOYSA-N 0.000 claims description 6
- UFNLOWRQRUZWKF-UHFFFAOYSA-N 4-[2-[2-(4-ethyl-4-hydroxyoctyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCC(O)(CC)CCCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 UFNLOWRQRUZWKF-UHFFFAOYSA-N 0.000 claims description 6
- KEQOYEUKTHDSDS-FNORWQNLSA-N 4-[2-[2-[(e)-4-hydroxynon-2-enyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCCC(O)\C=C\CN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 KEQOYEUKTHDSDS-FNORWQNLSA-N 0.000 claims description 6
- KALXDWPKUYNCLA-UHFFFAOYSA-N 4-[2-[2-[3-hydroxy-4-(3-methylphenyl)butyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CC1=CC=CC(CC(O)CCN2N(C(=O)CC2)CCC=2C=CC(=CC=2)C(O)=O)=C1 KALXDWPKUYNCLA-UHFFFAOYSA-N 0.000 claims description 6
- GNZZMSRREAKILT-UHFFFAOYSA-N 4-[2-[2-[4-[1-(cyclopropylmethyl)cyclobutyl]-4-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C1CCC1(CC1CC1)C(O)CCCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 GNZZMSRREAKILT-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- LTKCOAAEGIFTID-UHFFFAOYSA-N 4-[2-[2-(4-hydroxyoctyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCC(O)CCCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 LTKCOAAEGIFTID-UHFFFAOYSA-N 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- INOWIYUOGGMVDM-UHFFFAOYSA-N 4-[2-[2-(4-hydroxy-6-methylheptyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CC(C)CC(O)CCCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 INOWIYUOGGMVDM-UHFFFAOYSA-N 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 150000001540 azides Chemical class 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- JVPGVILOMSPMMY-UHFFFAOYSA-N 4-[2-[2-(3-hydroxy-4-phenylbutyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C=1C=CC=CC=1CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 JVPGVILOMSPMMY-UHFFFAOYSA-N 0.000 claims description 3
- CALFSRIGIOMZFM-UHFFFAOYSA-N 4-[2-[2-(4-hydroxy-4,7-dimethyloctyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CC(C)CCC(C)(O)CCCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 CALFSRIGIOMZFM-UHFFFAOYSA-N 0.000 claims description 3
- ZLJYTBPSXYKRKL-UHFFFAOYSA-N 4-[2-[2-(4-hydroxy-5-methyloctyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCC(C)C(O)CCCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 ZLJYTBPSXYKRKL-UHFFFAOYSA-N 0.000 claims description 3
- KDVFFCPULSQTQN-UHFFFAOYSA-N 4-[2-[2-[3-hydroxy-4-(3-iodophenyl)butyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C=1C=CC(I)=CC=1CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 KDVFFCPULSQTQN-UHFFFAOYSA-N 0.000 claims description 3
- NJNRRASCYIZRMY-UHFFFAOYSA-N 4-[2-[2-[4-(1,3-benzodioxol-5-yl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C=1C=C2OCOC2=CC=1CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 NJNRRASCYIZRMY-UHFFFAOYSA-N 0.000 claims description 3
- MMKYRZFPISEJKE-UHFFFAOYSA-N 4-[2-[2-[4-(3-bromophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C=1C=CC(Br)=CC=1CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 MMKYRZFPISEJKE-UHFFFAOYSA-N 0.000 claims description 3
- HVIXFTUMIDKUHX-UHFFFAOYSA-N 4-[2-[2-[4-(3-chlorophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C=1C=CC(Cl)=CC=1CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 HVIXFTUMIDKUHX-UHFFFAOYSA-N 0.000 claims description 3
- XZXVFMOGPSLDSM-UHFFFAOYSA-N 4-[2-[2-[4-(3-fluorophenyl)-3-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C=1C=CC(F)=CC=1CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 XZXVFMOGPSLDSM-UHFFFAOYSA-N 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 239000002871 fertility agent Substances 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- ZOMMPOGASDFZJV-UWJYYQICSA-N 4-[2-[2-[(3s,4s)-3-hydroxy-4-phenylpentyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C([C@H](O)[C@@H](C)C=1C=CC=CC=1)CN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 ZOMMPOGASDFZJV-UWJYYQICSA-N 0.000 claims description 2
- ZOMMPOGASDFZJV-OQHSHRKDSA-N 4-[2-[2-[(4r)-3-hydroxy-4-phenylpentyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound OC([C@H](C)C=1C=CC=CC=1)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 ZOMMPOGASDFZJV-OQHSHRKDSA-N 0.000 claims description 2
- XXHJUODZNGBFDI-UHFFFAOYSA-N 4-[2-[2-[3-hydroxy-4-[3-(trifluoromethoxy)phenyl]butyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C=1C=CC(OC(F)(F)F)=CC=1CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 XXHJUODZNGBFDI-UHFFFAOYSA-N 0.000 claims description 2
- UCAFZBFLCPWPLH-UHFFFAOYSA-N 4-[2-[2-[3-hydroxy-4-[3-(trifluoromethyl)phenyl]butyl]-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound C=1C=CC(C(F)(F)F)=CC=1CC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 UCAFZBFLCPWPLH-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims 2
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 claims 1
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 claims 1
- 102000009151 Luteinizing Hormone Human genes 0.000 claims 1
- 108010073521 Luteinizing Hormone Proteins 0.000 claims 1
- 208000011707 Ovulation disease Diseases 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 229940028334 follicle stimulating hormone Drugs 0.000 claims 1
- 229940040129 luteinizing hormone Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 49
- 238000011282 treatment Methods 0.000 abstract description 40
- NDGRWYRVNANFNB-UHFFFAOYSA-N pyrazolidin-3-one Chemical class O=C1CCNN1 NDGRWYRVNANFNB-UHFFFAOYSA-N 0.000 abstract description 19
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- 230000023555 blood coagulation Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 278
- 239000000243 solution Substances 0.000 description 218
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 143
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- 239000000203 mixture Substances 0.000 description 113
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 82
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
- 239000012267 brine Substances 0.000 description 62
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 62
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 60
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- 125000004432 carbon atom Chemical group C* 0.000 description 56
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- DBHOTPUMRDMPJQ-UHFFFAOYSA-N methyl 4-[2-[2-(4-hydroxy-4-methylnonyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCCC(C)(O)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 DBHOTPUMRDMPJQ-UHFFFAOYSA-N 0.000 description 5
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- NKBOAXUGPIMYAA-UHFFFAOYSA-N methyl 4-[2-[2-(3-cyclobutyl-3-hydroxypropyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCC(O)C1CCC1 NKBOAXUGPIMYAA-UHFFFAOYSA-N 0.000 description 1
- AUQUEKQUKQVRTD-UHFFFAOYSA-N methyl 4-[2-[2-(3-cyclobutyl-3-oxopropyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCC(=O)C1CCC1 AUQUEKQUKQVRTD-UHFFFAOYSA-N 0.000 description 1
- NCLDGMWHWMMIGK-UHFFFAOYSA-N methyl 4-[2-[2-(3-hydroxy-5-methylhexyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCC(O)CC(C)C NCLDGMWHWMMIGK-UHFFFAOYSA-N 0.000 description 1
- AJVLCBDBOKCCIQ-UHFFFAOYSA-N methyl 4-[2-[2-(4-ethyl-4-hydroxyoctyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCC(O)(CC)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 AJVLCBDBOKCCIQ-UHFFFAOYSA-N 0.000 description 1
- MPUNBPOVYKDPFG-UHFFFAOYSA-N methyl 4-[2-[2-(4-hydroxy-4-methylheptyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCC(C)(O)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 MPUNBPOVYKDPFG-UHFFFAOYSA-N 0.000 description 1
- FJFYKTHRDGTVIM-UHFFFAOYSA-N methyl 4-[2-[2-(4-hydroxynon-2-ynyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCCC(O)C#CCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 FJFYKTHRDGTVIM-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A—HUMAN NECESSITIES
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- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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- A—HUMAN NECESSITIES
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D231/08—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms
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| US33604801P | 2001-10-23 | 2001-10-23 | |
| PCT/US2002/033964 WO2003035064A1 (en) | 2001-10-23 | 2002-10-23 | Pyrazolidinone compounds as ligands of the prostaglandin ep2 and/or ep4 receptors |
Publications (3)
| Publication Number | Publication Date |
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| JP2005509632A JP2005509632A (ja) | 2005-04-14 |
| JP2005509632A5 JP2005509632A5 (OSRAM) | 2006-01-05 |
| JP4550417B2 true JP4550417B2 (ja) | 2010-09-22 |
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| EP (1) | EP1439837B1 (OSRAM) |
| JP (1) | JP4550417B2 (OSRAM) |
| AT (1) | ATE391503T1 (OSRAM) |
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| DE (1) | DE60226051T2 (OSRAM) |
| ES (1) | ES2305310T3 (OSRAM) |
| IL (2) | IL161581A0 (OSRAM) |
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| ES2393321T3 (es) | 2002-10-10 | 2012-12-20 | Ono Pharmaceutical Co., Ltd. | Promotores de la producción de factores de reparación endógenos |
| US7531533B2 (en) | 2005-01-27 | 2009-05-12 | Asahi Kasei Pharma Corporation | 6-Membered heterocyclic compound and use thereof |
| CA2596003C (en) * | 2005-01-27 | 2012-12-18 | Asahi Kasei Pharma Corporation | Six-membered heterocyclic compound and use thereof |
| US7893107B2 (en) | 2005-11-30 | 2011-02-22 | Allergan, Inc. | Therapeutic methods using prostaglandin EP4 agonist components |
| US7557095B2 (en) * | 2006-05-12 | 2009-07-07 | Allergan, Inc. | Therapeutic compounds |
| CA2660396A1 (en) * | 2006-08-09 | 2008-02-21 | Allergan, Inc. | Therapeutic amides and related compounds |
| US7507833B2 (en) * | 2006-08-10 | 2009-03-24 | Allergan, Inc. | Therapeutic N-aryl or N-heteroaryl pyrazolidine and pyrazolidinone derivatives |
| WO2008136519A1 (ja) | 2007-05-08 | 2008-11-13 | National University Corporation, Hamamatsu University School Of Medicine | Ｅｐ４アゴニストを含有してなる細胞傷害性ｔ細胞の活性化剤 |
| EP2002834A1 (de) * | 2007-06-13 | 2008-12-17 | Bayer Schering Pharma Aktiengesellschaft | Aryl/Hetarylamide als Modulatoren des EP2-Rezeptors |
| EP2002838A1 (de) * | 2007-06-13 | 2008-12-17 | Bayer Schering Pharma AG | Verwendung von Aryl/Hetarylamid-Derivaten als Modulatoren des EP2-Rezeptors |
| EP2014287A1 (de) * | 2007-06-13 | 2009-01-14 | Bayer Schering Pharma Aktiengesellschaft | Verwendung von Zimtsäurederivaten als Modulatoren des EP2-Rezeptors |
| EP2003118A1 (de) * | 2007-06-13 | 2008-12-17 | Bayer Schering Pharma Aktiengesellschaft | Zimtsäurederivate als Modulatoren des EP2-Rezeptors |
| KR20110028584A (ko) * | 2008-05-09 | 2011-03-21 | 알러간, 인코포레이티드 | 치료학적인 ｎ-아릴 또는 ｎ-헤테로아릴 피라졸리딘 및 피라졸리딘온 유도체 |
| EP2149551A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | N-(Indol-3-ylalkyl)-(hetero)arylamidderivate als Modulatoren des EP2-Rezeptors |
| EP2149554A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma Aktiengesellschaft | Indolylamide als Modulatoren des EP2-Rezeptors |
| EP2149552A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | 5,6 substituierte Benzamid-Derivate als Modulatoren des EP2-Rezeptors |
| US8877758B2 (en) | 2010-04-08 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Combinations of medicaments, containing PDE4-inhibitors and EP4-receptor-antagonists |
| US20130225609A1 (en) * | 2010-04-08 | 2013-08-29 | Boehringer Ingelheim International Gmbh | Combinations of medicaments, containing pde4-inhibitors and ep4-receptor-antagonists |
| TW201326154A (zh) | 2011-11-28 | 2013-07-01 | 拜耳知識產權公司 | 作為ｅｐ２受體拮抗劑之新穎２ｈ－吲唑 |
| CN107802623B (zh) | 2012-07-19 | 2020-10-30 | 开曼化学股份有限公司 | 用于ep4介导的骨相关疾病和病症的二氟内酰胺组合物 |
| US20150272874A1 (en) | 2012-10-29 | 2015-10-01 | Cardio Incorporated | Pulmonary disease-specific therapeutic agent |
| WO2014144610A1 (en) | 2013-03-15 | 2014-09-18 | Cayman Chemical Company, Inc. | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
| EP2989098B1 (en) | 2013-03-15 | 2017-05-10 | Cayman Chemical Company, Incorporated | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
| CN105392505A (zh) | 2013-07-19 | 2016-03-09 | 开曼化学股份有限公司 | 用于促进骨生长的方法、系统和组合物 |
| US9968716B2 (en) | 2013-10-15 | 2018-05-15 | Ono Pharmaceutical Co., Ltd. | Drug-eluting stent graft |
| AU2018396402C1 (en) | 2017-12-25 | 2021-03-18 | Asahi Kasei Pharma Corporation | Nitrogen-containing 6-membered cyclic compound |
| AU2019387370A1 (en) | 2018-11-30 | 2021-06-10 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| US12304897B2 (en) | 2019-01-31 | 2025-05-20 | Kyorin Pharmaceutical Co., Ltd. | 15-PGDH inhibitors |
| GB202211234D0 (en) * | 2022-08-02 | 2022-09-14 | Heptares Therapeutics Ltd | Prostaglandin EP4 receptor agonist compounds |
| GB202211232D0 (en) | 2022-08-02 | 2022-09-14 | Heptares Therapeutics Ltd | Prostaglandin EP4 receptor agonist compounds |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2323193A1 (de) * | 1972-05-10 | 1973-11-22 | Du Pont | Pyrazolidinone |
| US3873566A (en) * | 1973-02-28 | 1975-03-25 | Du Pont | 3-Pyrazolidinones and pyrazolidines |
| DE2451160A1 (de) * | 1973-10-30 | 1975-05-07 | Du Pont | 3-pyrazolidinone und pyrazolidine |
| US4211876A (en) * | 1979-06-13 | 1980-07-08 | E. I. Du Pont De Nemours And Company | 3-Pyrazolidinone carboxamides |
| US5605814A (en) | 1993-08-31 | 1997-02-25 | Merck Frosst Canada Inc. | DNA encoding human prostaglandin receptor EP2 |
| GB9514160D0 (en) | 1994-07-25 | 1995-09-13 | Zeneca Ltd | Aromatic compounds |
| GB9417532D0 (en) | 1994-08-31 | 1994-10-19 | Zeneca Ltd | Aromatic compounds |
| TW434240B (en) | 1995-06-20 | 2001-05-16 | Zeneca Ltd | Aromatic compounds, preparation thereof and pharmaceutical composition comprising same |
| TW502026B (en) | 1995-06-20 | 2002-09-11 | Zeneca Ltd | Aromatic compounds useful as antagonists of e-type prostaglandins, processes for the preparation thereof, pharmaceutical compositions comprising the compounds, and intermediates |
| US5834468A (en) | 1995-07-07 | 1998-11-10 | Zeneca Limited | Substituted aryl and heteroaryl compounds as E-type prostaglandin antagonists |
| WO2000015608A1 (fr) | 1998-09-14 | 2000-03-23 | Ono Pharmaceutical Co., Ltd. | Derives e de phenyl-prostaglandine a substitution-φ et medicaments les contenant comme ingredient actif |
| US6211197B1 (en) | 1998-10-07 | 2001-04-03 | Merck Frosst Canada & Co. | Prostaglandin receptor ligands |
| EP1132086B1 (en) | 2000-01-31 | 2006-05-31 | Pfizer Products Inc. | Use of prostaglandin (PGE2) receptor 4 (EP4) selective agonists for the treatment of acute and chronic renal failure |
| US20010056060A1 (en) * | 2000-02-07 | 2001-12-27 | Cameron Kimberly O. | Treatment of osteoporsis with EP2/EP4 receptor selective agonists |
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2002
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- 2002-10-23 WO PCT/US2002/033964 patent/WO2003035064A1/en not_active Ceased
- 2002-10-23 IL IL16158102A patent/IL161581A0/xx unknown
- 2002-10-23 JP JP2003537631A patent/JP4550417B2/ja not_active Expired - Fee Related
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Also Published As
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| EP1439837A1 (en) | 2004-07-28 |
| IL161581A (en) | 2010-11-30 |
| DE60226051D1 (de) | 2008-05-21 |
| WO2003035064A1 (en) | 2003-05-01 |
| CA2463102C (en) | 2011-05-10 |
| DE60226051T2 (de) | 2009-05-20 |
| IL161581A0 (en) | 2004-09-27 |
| US7410991B2 (en) | 2008-08-12 |
| US20080234346A1 (en) | 2008-09-25 |
| ES2305310T3 (es) | 2008-11-01 |
| AU2002340282B2 (en) | 2007-08-09 |
| JP2005509632A (ja) | 2005-04-14 |
| CA2463102A1 (en) | 2003-05-01 |
| ATE391503T1 (de) | 2008-04-15 |
| EP1439837B1 (en) | 2008-04-09 |
| US20040254233A1 (en) | 2004-12-16 |
| US7863312B2 (en) | 2011-01-04 |
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