CA2463102C - Pyrazolidinone compounds as ligands of the prostaglandin ep2 and/or ep4 receptors - Google Patents
Pyrazolidinone compounds as ligands of the prostaglandin ep2 and/or ep4 receptors Download PDFInfo
- Publication number
- CA2463102C CA2463102C CA2463102A CA2463102A CA2463102C CA 2463102 C CA2463102 C CA 2463102C CA 2463102 A CA2463102 A CA 2463102A CA 2463102 A CA2463102 A CA 2463102A CA 2463102 C CA2463102 C CA 2463102C
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- CA
- Canada
- Prior art keywords
- ethyl
- oxopyrazolidin
- benzoic acid
- alkyl
- groups
- 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.)
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- NDGRWYRVNANFNB-UHFFFAOYSA-N pyrazolidin-3-one Chemical class O=C1CCNN1 NDGRWYRVNANFNB-UHFFFAOYSA-N 0.000 title abstract description 20
- 101150109738 Ptger4 gene Proteins 0.000 title abstract description 14
- 150000003180 prostaglandins Chemical class 0.000 title abstract description 14
- 239000003446 ligand Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 229
- 238000011282 treatment Methods 0.000 claims abstract description 37
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- 208000005171 Dysmenorrhea Diseases 0.000 claims abstract description 9
- 206010013935 Dysmenorrhoea Diseases 0.000 claims abstract description 9
- 206010020772 Hypertension Diseases 0.000 claims abstract description 9
- 201000001880 Sexual dysfunction Diseases 0.000 claims abstract description 9
- 231100000872 sexual dysfunction Toxicity 0.000 claims abstract description 9
- 230000023555 blood coagulation Effects 0.000 claims abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
- 230000001066 destructive effect Effects 0.000 claims abstract description 7
- 208000002296 eclampsia Diseases 0.000 claims abstract description 7
- 201000011461 pre-eclampsia Diseases 0.000 claims abstract description 7
- 208000012610 eosinophil disease Diseases 0.000 claims abstract description 6
- -1 cyano, hydroxyl Chemical group 0.000 claims description 65
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 40
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
- 125000000217 alkyl group Chemical group 0.000 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 23
- 239000005711 Benzoic acid Substances 0.000 claims description 21
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 13
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- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 11
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
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- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
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- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000304 alkynyl group Chemical group 0.000 claims description 8
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
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- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000001589 carboacyl group Chemical group 0.000 claims description 6
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- 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 5
- 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 5
- 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 5
- 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
- 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 5
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 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 4
- PAVYSSGJRYCIIJ-UHFFFAOYSA-N 4-[2-[2-(3-hydroxyoctyl)-5-oxopyrazolidin-1-yl]ethyl]benzoic acid Chemical compound CCCCCC(O)CCN1CCC(=O)N1CCC1=CC=C(C(O)=O)C=C1 PAVYSSGJRYCIIJ-UHFFFAOYSA-N 0.000 claims description 4
- 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
- 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 4
- 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 4
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- 125000004104 aryloxy group Chemical group 0.000 claims description 4
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- 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
- 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 3
- 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 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
- 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 3
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- 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
- 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
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- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 125000005946 imidazo[1,2-a]pyridyl group Chemical group 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000005990 isobenzothienyl group Chemical group 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- LROBJRRFCPYLIT-UHFFFAOYSA-M magnesium;ethyne;bromide Chemical compound [Mg+2].[Br-].[C-]#C LROBJRRFCPYLIT-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
- HNNUQHJWFIPTLJ-UHFFFAOYSA-N methyl 4-(2-bromoethyl)benzoate Chemical compound COC(=O)C1=CC=C(CCBr)C=C1 HNNUQHJWFIPTLJ-UHFFFAOYSA-N 0.000 description 1
- NWYMKMRYNCIGAW-UHFFFAOYSA-N methyl 4-[2-(5-oxopyrazolidin-1-yl)ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1 NWYMKMRYNCIGAW-UHFFFAOYSA-N 0.000 description 1
- 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
- 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
- KLLYMKRXJAHIRZ-UHFFFAOYSA-N methyl 4-[2-[2-(4-hydroxy-4,7-dimethyloctyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCCC(C)(O)CCC(C)C KLLYMKRXJAHIRZ-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
- POAXYWHPKVTOFT-UHFFFAOYSA-N methyl 4-[2-[2-(4-hydroxynonyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCCC(O)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 POAXYWHPKVTOFT-UHFFFAOYSA-N 0.000 description 1
- LKNWDNUGYXOXPP-UHFFFAOYSA-N methyl 4-[2-[2-(4-hydroxyoctyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCC(O)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 LKNWDNUGYXOXPP-UHFFFAOYSA-N 0.000 description 1
- GUMHMFKRILHNLH-UHFFFAOYSA-N methyl 4-[2-[2-(5-methyl-3-oxohexyl)-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCC(=O)CC(C)C GUMHMFKRILHNLH-UHFFFAOYSA-N 0.000 description 1
- HMBSBHRITOGNAY-UHFFFAOYSA-N methyl 4-[2-[2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]ethyl]benzoate Chemical compound COC(=O)C1=CC=C(CCNNC(=O)OC(C)(C)C)C=C1 HMBSBHRITOGNAY-UHFFFAOYSA-N 0.000 description 1
- POAXYWHPKVTOFT-FQEVSTJZSA-N methyl 4-[2-[2-[(4s)-4-hydroxynonyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCC[C@H](O)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 POAXYWHPKVTOFT-FQEVSTJZSA-N 0.000 description 1
- ZENVLSYKWVOWIV-SOFGYWHQSA-N methyl 4-[2-[2-[(e)-4-hydroxynon-2-enyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCCC(O)\C=C\CN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 ZENVLSYKWVOWIV-SOFGYWHQSA-N 0.000 description 1
- ZENVLSYKWVOWIV-VURMDHGXSA-N methyl 4-[2-[2-[(z)-4-hydroxynon-2-enyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCCC(O)\C=C/CN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 ZENVLSYKWVOWIV-VURMDHGXSA-N 0.000 description 1
- DZTUYZMEUWMMEO-UHFFFAOYSA-N methyl 4-[2-[2-[3-hydroxy-4-(3-methylphenyl)butyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCC(O)CC1=CC=CC(C)=C1 DZTUYZMEUWMMEO-UHFFFAOYSA-N 0.000 description 1
- ZESHBQCNBHIALE-UHFFFAOYSA-N methyl 4-[2-[2-[4-(1-ethylcyclobutyl)-4-hydroxybutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1CC(=O)N(CCC=2C=CC(=CC=2)C(=O)OC)N1CCCC(O)C1(CC)CCC1 ZESHBQCNBHIALE-UHFFFAOYSA-N 0.000 description 1
- SZSNAUYZXVBGBG-UHFFFAOYSA-N methyl 4-[2-[2-[4-(3-methylphenyl)-3-oxobutyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCC(=O)CC1=CC=CC(C)=C1 SZSNAUYZXVBGBG-UHFFFAOYSA-N 0.000 description 1
- UECRBTCJNGJQNG-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxy-4,7-dimethyloctyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCCC(C)(CCC(C)C)O[Si](C)(C)C(C)(C)C UECRBTCJNGJQNG-UHFFFAOYSA-N 0.000 description 1
- IDVNHKBEXJNSFR-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxy-4-(1-ethylcyclobutyl)butyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1CC(=O)N(CCC=2C=CC(=CC=2)C(=O)OC)N1CCCC(O[Si](C)(C)C(C)(C)C)C1(CC)CCC1 IDVNHKBEXJNSFR-UHFFFAOYSA-N 0.000 description 1
- INKPEGQXXYINKS-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxy-4-ethyloct-2-ynyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCC(CC)(O[Si](C)(C)C(C)(C)C)C#CCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 INKPEGQXXYINKS-UHFFFAOYSA-N 0.000 description 1
- JJPAAKHAAXYCBG-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxy-4-ethyloctyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCC(CC)(O[Si](C)(C)C(C)(C)C)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 JJPAAKHAAXYCBG-UHFFFAOYSA-N 0.000 description 1
- XMUOYBIWERBMFS-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxy-4-methylheptyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CC(C)(C)[Si](C)(C)OC(C)(CCC)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 XMUOYBIWERBMFS-UHFFFAOYSA-N 0.000 description 1
- ONDHPVXEOPHXAR-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxy-5-methyloctyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCC(C)C(O[Si](C)(C)C(C)(C)C)CCCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 ONDHPVXEOPHXAR-UHFFFAOYSA-N 0.000 description 1
- HSZDHSQLHQFLOK-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxy-6-methylhept-2-ynyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CC#CC(CC(C)C)O[Si](C)(C)C(C)(C)C HSZDHSQLHQFLOK-UHFFFAOYSA-N 0.000 description 1
- WUPHAROXQNRRAP-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxy-6-methylheptyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1CCCC(CC(C)C)O[Si](C)(C)C(C)(C)C WUPHAROXQNRRAP-UHFFFAOYSA-N 0.000 description 1
- SYYOMHRJBFPGRC-UHFFFAOYSA-N methyl 4-[2-[2-[4-[tert-butyl(dimethyl)silyl]oxynon-2-ynyl]-5-oxopyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCCC(O[Si](C)(C)C(C)(C)C)C#CCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 SYYOMHRJBFPGRC-UHFFFAOYSA-N 0.000 description 1
- NEVCPSXEQHAUJE-UHFFFAOYSA-N methyl 4-[2-[5-oxo-2-(3-oxooctyl)pyrazolidin-1-yl]ethyl]benzoate Chemical compound CCCCCC(=O)CCN1CCC(=O)N1CCC1=CC=C(C(=O)OC)C=C1 NEVCPSXEQHAUJE-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- CKYUMEGJFNPHQR-UHFFFAOYSA-N n,n-diethylcyclobutanecarboxamide Chemical compound CCN(CC)C(=O)C1CCC1 CKYUMEGJFNPHQR-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- UPSCSLXQWAMPEG-UHFFFAOYSA-N n-methoxy-n-methyl-2-(3-methylphenyl)acetamide Chemical compound CON(C)C(=O)CC1=CC=CC(C)=C1 UPSCSLXQWAMPEG-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- VUGRNZHKYVHZSN-UHFFFAOYSA-N oct-1-yn-3-ol Chemical compound CCCCCC(O)C#C VUGRNZHKYVHZSN-UHFFFAOYSA-N 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000009117 preventive therapy Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000017953 prostanoid receptors Human genes 0.000 description 1
- 108050007059 prostanoid receptors Proteins 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000029865 regulation of blood pressure Effects 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- CYFLXLSBHQBMFT-UHFFFAOYSA-N sulfamoxole Chemical group O1C(C)=C(C)N=C1NS(=O)(=O)C1=CC=C(N)C=C1 CYFLXLSBHQBMFT-UHFFFAOYSA-N 0.000 description 1
- 150000003455 sulfinic acids Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- VUUDTUCWJNLDJM-UHFFFAOYSA-N tert-butyl 2-[2-(4-methoxycarbonylphenyl)ethyl]-3-oxopyrazolidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1CCN1C(=O)CCN1C(=O)OC(C)(C)C VUUDTUCWJNLDJM-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- JTUXNRYXCLOBFT-UHFFFAOYSA-N tert-butyl-(3,5-dimethylhex-1-yn-3-yloxy)-dimethylsilane Chemical compound CC(C)CC(C)(C#C)O[Si](C)(C)C(C)(C)C JTUXNRYXCLOBFT-UHFFFAOYSA-N 0.000 description 1
- CIRNQEYHHPRMDV-UHFFFAOYSA-N tert-butyl-(3-ethylhept-1-yn-3-yloxy)-dimethylsilane Chemical compound CCCCC(CC)(C#C)O[Si](C)(C)C(C)(C)C CIRNQEYHHPRMDV-UHFFFAOYSA-N 0.000 description 1
- RLFIYYHGGBQZIQ-UHFFFAOYSA-N tert-butyl-[1-(1-ethylcyclobutyl)prop-2-ynoxy]-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC(C#C)C1(CC)CCC1 RLFIYYHGGBQZIQ-UHFFFAOYSA-N 0.000 description 1
- GSBVLLBHXXTWKJ-UHFFFAOYSA-N tert-butyl-[1-[1-(cyclopropylmethyl)cyclobutyl]prop-2-ynoxy]-dimethylsilane Chemical compound C1CC1CC1(C(C#C)O[Si](C)(C)C(C)(C)C)CCC1 GSBVLLBHXXTWKJ-UHFFFAOYSA-N 0.000 description 1
- WRKXJSGDOAXJOJ-UHFFFAOYSA-N tert-butyl-dimethyl-(5-methylhex-1-yn-3-yloxy)silane Chemical compound CC(C)CC(C#C)O[Si](C)(C)C(C)(C)C WRKXJSGDOAXJOJ-UHFFFAOYSA-N 0.000 description 1
- MMKOSVMWXHDGEI-ZDUSSCGKSA-N tert-butyl-dimethyl-[(3r)-oct-1-yn-3-yl]oxysilane Chemical compound CCCCC[C@H](C#C)O[Si](C)(C)C(C)(C)C MMKOSVMWXHDGEI-ZDUSSCGKSA-N 0.000 description 1
- MMKOSVMWXHDGEI-UHFFFAOYSA-N tert-butyl-dimethyl-oct-1-yn-3-yloxysilane Chemical compound CCCCCC(C#C)O[Si](C)(C)C(C)(C)C MMKOSVMWXHDGEI-UHFFFAOYSA-N 0.000 description 1
- MOYCAPFGOXDUQD-UHFFFAOYSA-N tert-butyl-hept-1-yn-3-yloxy-dimethylsilane Chemical compound CCCCC(C#C)O[Si](C)(C)C(C)(C)C MOYCAPFGOXDUQD-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
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| US33604801P | 2001-10-23 | 2001-10-23 | |
| US60/336,048 | 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 (2)
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| CA2463102A1 CA2463102A1 (en) | 2003-05-01 |
| CA2463102C true CA2463102C (en) | 2011-05-10 |
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| ES2584606T3 (es) | 2002-10-10 | 2016-09-28 | Ono Pharmaceutical Co., Ltd. | Microesferas que comprenden ONO-1301 |
| US7531533B2 (en) | 2005-01-27 | 2009-05-12 | Asahi Kasei Pharma Corporation | 6-Membered heterocyclic compound and use thereof |
| EP1847533B1 (en) * | 2005-01-27 | 2013-08-14 | Asahi Kasei Pharma Corporation | Six-membered heterocyclic compound and the 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 |
| ATE502914T1 (de) * | 2006-08-09 | 2011-04-15 | Allergan Inc | Therapeutische amide und entsprechende verbindungen |
| US7507833B2 (en) * | 2006-08-10 | 2009-03-24 | Allergan, Inc. | Therapeutic N-aryl or N-heteroaryl pyrazolidine and pyrazolidinone derivatives |
| AU2008246579A1 (en) | 2007-05-08 | 2008-11-13 | National University Corporation, Hamamatsu University School Of Medicine | Cytotoxic T cell activator comprising EP4 agonist |
| EP2002838A1 (de) * | 2007-06-13 | 2008-12-17 | Bayer Schering Pharma AG | Verwendung von Aryl/Hetarylamid-Derivaten als Modulatoren des EP2-Rezeptors |
| EP2003118A1 (de) * | 2007-06-13 | 2008-12-17 | Bayer Schering Pharma Aktiengesellschaft | Zimtsäurederivate als Modulatoren des EP2-Rezeptors |
| EP2002834A1 (de) * | 2007-06-13 | 2008-12-17 | Bayer Schering Pharma Aktiengesellschaft | Aryl/Hetarylamide 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 |
| JP2011519937A (ja) * | 2008-05-09 | 2011-07-14 | アラーガン インコーポレイテッド | 治療用ｎ‐アリールまたはｎ‐ヘテロアリールピラゾリジンおよびピラゾリジノン誘導体 |
| EP2149551A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | N-(Indol-3-ylalkyl)-(hetero)arylamidderivate 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 |
| EP2149554A1 (de) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma Aktiengesellschaft | Indolylamide als Modulatoren des EP2-Rezeptors |
| EP2555774B1 (de) * | 2010-04-08 | 2015-10-21 | Boehringer Ingelheim International GmbH | Arnzeimittelkombinationen enthaltend pde4-inhibitoren und ep4-rezeptor-antagonisten |
| EP2555773A1 (de) | 2010-04-08 | 2013-02-13 | Boehringer Ingelheim International GmbH | Arzneimittelkombinationen enthaltend pde4-inhibitoren und ep4-rezeptor-antagonisten |
| 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 |
| EP2913047B1 (en) | 2012-10-29 | 2019-05-08 | Cardio Incorporated | Pulmonary disease-specific therapeutic agent |
| EP3235817B1 (en) | 2013-03-15 | 2018-12-12 | Cayman Chemical Company, Incorporated | Lactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated diseases and conditions |
| 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 |
| JP2016527006A (ja) | 2013-07-19 | 2016-09-08 | ケイマン ケミカル カンパニー， インコーポレーテッド | 骨成長を促進するための方法、システム、及び組成物 |
| US9968716B2 (en) | 2013-10-15 | 2018-05-15 | Ono Pharmaceutical Co., Ltd. | Drug-eluting stent graft |
| CN111511736B (zh) | 2017-12-25 | 2023-03-24 | 旭化成制药株式会社 | 含氮6元环化合物 |
| CA3121202A1 (en) | 2018-11-30 | 2020-06-04 | Nuvation Bio Inc. | Pyrrole and pyrazole compounds and methods of use thereof |
| TWI834795B (zh) | 2019-01-08 | 2024-03-11 | 日商杏林製藥股份有限公司 | 15-pgdh抑制劑 |
| EP3917911A1 (en) | 2019-01-31 | 2021-12-08 | Kyorin Pharmaceutical Co., Ltd. | 15-pgdh inhibitors |
| GB202211232D0 (en) | 2022-08-02 | 2022-09-14 | Heptares Therapeutics Ltd | Prostaglandin EP4 receptor agonist compounds |
| GB202211234D0 (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 |
| 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 |
| TW434240B (en) | 1995-06-20 | 2001-05-16 | Zeneca Ltd | Aromatic compounds, preparation thereof and pharmaceutical composition comprising same |
| US5834468A (en) | 1995-07-07 | 1998-11-10 | Zeneca Limited | Substituted aryl and heteroaryl compounds as E-type prostaglandin antagonists |
| US6586468B1 (en) * | 1998-09-14 | 2003-07-01 | Ono Pharmaceutical Co., Ltd. | ω-substituted phenyl-prostaglandin E derivatives and drugs containing the same as the active ingredient |
| US6211197B1 (en) * | 1998-10-07 | 2001-04-03 | Merck Frosst Canada & Co. | Prostaglandin receptor ligands |
| DE60120007T2 (de) * | 2000-01-31 | 2006-11-16 | Pfizer Products Inc., Groton | Verwendung von Aktivatoren des Prostaglandinrezeptores 4 zur Behandlung von akuter oder chronischer Niereninsuffizienz |
| US20010056060A1 (en) * | 2000-02-07 | 2001-12-27 | Cameron Kimberly O. | Treatment of osteoporsis with EP2/EP4 receptor selective agonists |
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Also Published As
| Publication number | Publication date |
|---|---|
| JP4550417B2 (ja) | 2010-09-22 |
| CA2463102A1 (en) | 2003-05-01 |
| DE60226051T2 (de) | 2009-05-20 |
| EP1439837A1 (en) | 2004-07-28 |
| DE60226051D1 (de) | 2008-05-21 |
| JP2005509632A (ja) | 2005-04-14 |
| WO2003035064A1 (en) | 2003-05-01 |
| ES2305310T3 (es) | 2008-11-01 |
| IL161581A (en) | 2010-11-30 |
| AU2002340282B2 (en) | 2007-08-09 |
| IL161581A0 (en) | 2004-09-27 |
| ATE391503T1 (de) | 2008-04-15 |
| US20080234346A1 (en) | 2008-09-25 |
| EP1439837B1 (en) | 2008-04-09 |
| US7863312B2 (en) | 2011-01-04 |
| US20040254233A1 (en) | 2004-12-16 |
| US7410991B2 (en) | 2008-08-12 |
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