NO316733B1 - Prostaglandinagonister og anvendelse derav, samt farmasoytisk preparat og sett - Google Patents
Prostaglandinagonister og anvendelse derav, samt farmasoytisk preparat og sett Download PDFInfo
- Publication number
- NO316733B1 NO316733B1 NO20001754A NO20001754A NO316733B1 NO 316733 B1 NO316733 B1 NO 316733B1 NO 20001754 A NO20001754 A NO 20001754A NO 20001754 A NO20001754 A NO 20001754A NO 316733 B1 NO316733 B1 NO 316733B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- pharmaceutically acceptable
- acceptable salt
- acid
- methyl
- Prior art date
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- 241000124008 Mammalia Species 0.000 claims description 24
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- WPZJMCWRTJTJSH-UHFFFAOYSA-N methyl 3-[3-[[(1-methylimidazol-4-yl)sulfonyl-[(4-pyrimidin-2-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=CN=2)S(=O)(=O)C=2N=CN(C)C=2)=C1 WPZJMCWRTJTJSH-UHFFFAOYSA-N 0.000 description 1
- MGHAZIJIRKIWDE-UHFFFAOYSA-N methyl 3-[3-[[(4-chlorophenyl)sulfonyl-[(4-pyrazin-2-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=NC=2)S(=O)(=O)C=2C=CC(Cl)=CC=2)=C1 MGHAZIJIRKIWDE-UHFFFAOYSA-N 0.000 description 1
- UGYORFFMRUCWMN-UHFFFAOYSA-N methyl 3-[3-[[(4-chlorophenyl)sulfonyl-[(4-pyrimidin-2-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=CN=2)S(=O)(=O)C=2C=CC(Cl)=CC=2)=C1 UGYORFFMRUCWMN-UHFFFAOYSA-N 0.000 description 1
- JAAMKLYFJGXPTJ-UHFFFAOYSA-N methyl 3-[3-[[(4-chlorophenyl)sulfonyl-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2SC=CN=2)S(=O)(=O)C=2C=CC(Cl)=CC=2)=C1 JAAMKLYFJGXPTJ-UHFFFAOYSA-N 0.000 description 1
- PQUUZVVJNFUREW-UHFFFAOYSA-N methyl 3-[3-[[(4-phenylphenyl)methyl-pyridin-2-ylsulfonylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=CC=CC=2)S(=O)(=O)C=2N=CC=CC=2)=C1 PQUUZVVJNFUREW-UHFFFAOYSA-N 0.000 description 1
- RHUWQTQKJVBHAW-UHFFFAOYSA-N methyl 3-[3-[[(4-pyrazin-2-ylphenyl)methyl-pyridin-2-ylsulfonylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=NC=2)S(=O)(=O)C=2N=CC=CC=2)=C1 RHUWQTQKJVBHAW-UHFFFAOYSA-N 0.000 description 1
- VIHFBEKKNGOWAK-UHFFFAOYSA-N methyl 3-[3-[[(4-pyrazol-1-ylphenyl)methyl-(1,3-thiazol-2-ylsulfonyl)amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)N2N=CC=C2)S(=O)(=O)C=2SC=CN=2)=C1 VIHFBEKKNGOWAK-UHFFFAOYSA-N 0.000 description 1
- WZTLGNWYQWIOSE-UHFFFAOYSA-N methyl 3-[3-[[(4-pyrazol-1-ylphenyl)methyl-pyridin-2-ylsulfonylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)N2N=CC=C2)S(=O)(=O)C=2N=CC=CC=2)=C1 WZTLGNWYQWIOSE-UHFFFAOYSA-N 0.000 description 1
- VDGOLKIQDBHYIS-UHFFFAOYSA-N methyl 3-[3-[[(4-pyrazol-1-ylphenyl)methyl-pyridin-3-ylsulfonylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)N2N=CC=C2)S(=O)(=O)C=2C=NC=CC=2)=C1 VDGOLKIQDBHYIS-UHFFFAOYSA-N 0.000 description 1
- UMNQCRQBFXQBES-UHFFFAOYSA-N methyl 3-[3-[[(4-pyridin-3-ylphenyl)methyl-pyridin-2-ylsulfonylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=NC=CC=2)S(=O)(=O)C=2N=CC=CC=2)=C1 UMNQCRQBFXQBES-UHFFFAOYSA-N 0.000 description 1
- LAAYEWJZLGTYNX-UHFFFAOYSA-N methyl 3-[3-[[(4-pyrimidin-2-ylphenyl)methyl-(1,3-thiazol-2-ylsulfonyl)amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=CN=2)S(=O)(=O)C=2SC=CN=2)=C1 LAAYEWJZLGTYNX-UHFFFAOYSA-N 0.000 description 1
- PIWNFUJDRUGBEF-UHFFFAOYSA-N methyl 3-[3-[[(4-tert-butylphenyl)methyl-(1,3-thiazol-2-ylsulfonyl)amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C(C)(C)C)S(=O)(=O)C=2SC=CN=2)=C1 PIWNFUJDRUGBEF-UHFFFAOYSA-N 0.000 description 1
- CPIHQEMNORFIPJ-UHFFFAOYSA-N methyl 3-[3-[[(4-tert-butylphenyl)methyl-pyridin-2-ylsulfonylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C(C)(C)C)S(=O)(=O)C=2N=CC=CC=2)=C1 CPIHQEMNORFIPJ-UHFFFAOYSA-N 0.000 description 1
- QBKQAUWQMXAZJL-UHFFFAOYSA-N methyl 3-[3-[[1,3-benzodioxol-5-ylmethyl-(4-fluorophenyl)sulfonylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=C3OCOC3=CC=2)S(=O)(=O)C=2C=CC(F)=CC=2)=C1 QBKQAUWQMXAZJL-UHFFFAOYSA-N 0.000 description 1
- INGRLAKDUDGESX-UHFFFAOYSA-N methyl 3-[3-[[1-benzofuran-2-ylmethyl-(4-fluorophenyl)sulfonylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2OC3=CC=CC=C3C=2)S(=O)(=O)C=2C=CC(F)=CC=2)=C1 INGRLAKDUDGESX-UHFFFAOYSA-N 0.000 description 1
- BPAYPYKUCRJQKE-UHFFFAOYSA-N methyl 3-[3-[[2,3-dihydro-1,4-benzodioxin-6-ylmethyl(pyridin-2-ylsulfonyl)amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=C3OCCOC3=CC=2)S(=O)(=O)C=2N=CC=CC=2)=C1 BPAYPYKUCRJQKE-UHFFFAOYSA-N 0.000 description 1
- KHLFKVMWEGGGEF-UHFFFAOYSA-N methyl 3-[3-[[2,3-dihydro-1-benzofuran-5-ylmethyl(methylsulfonyl)amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=C3CCOC3=CC=2)S(C)(=O)=O)=C1 KHLFKVMWEGGGEF-UHFFFAOYSA-N 0.000 description 1
- QABNVPXQCZZSHX-UHFFFAOYSA-N methyl 3-[3-[[[4-(2-methylpropyl)phenyl]methylamino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CNCC=2C=CC(CC(C)C)=CC=2)=C1 QABNVPXQCZZSHX-UHFFFAOYSA-N 0.000 description 1
- FJSDUNSGLHUNDH-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl(1,3-benzodioxol-5-ylmethyl)amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=C3OCOC3=CC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 FJSDUNSGLHUNDH-UHFFFAOYSA-N 0.000 description 1
- JNUTYSXZFKAJHC-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl(1-benzofuran-2-ylmethyl)amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2OC3=CC=CC=C3C=2)S(=O)(=O)C=2C=CC=CC=2)=C1 JNUTYSXZFKAJHC-UHFFFAOYSA-N 0.000 description 1
- SIEUPCDOXWJTRC-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl(2,3-dihydro-1-benzofuran-5-ylmethyl)amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=C3CCOC3=CC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 SIEUPCDOXWJTRC-UHFFFAOYSA-N 0.000 description 1
- VXKGQJMPOGKMME-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[(4-phenylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=CC=CC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 VXKGQJMPOGKMME-UHFFFAOYSA-N 0.000 description 1
- WPRWBKAXCDDMGD-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[(4-pyrazin-2-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=NC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 WPRWBKAXCDDMGD-UHFFFAOYSA-N 0.000 description 1
- ZEQJAYLTLQVGBB-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[(4-pyrazol-1-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)N2N=CC=C2)S(=O)(=O)C=2C=CC=CC=2)=C1 ZEQJAYLTLQVGBB-UHFFFAOYSA-N 0.000 description 1
- IUHQAVHPJQERSA-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[(4-pyridin-3-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=NC=CC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 IUHQAVHPJQERSA-UHFFFAOYSA-N 0.000 description 1
- KYORCOKOHIJTKK-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[(4-pyrimidin-2-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=CN=2)S(=O)(=O)C=2C=CC=CC=2)=C1 KYORCOKOHIJTKK-UHFFFAOYSA-N 0.000 description 1
- ZMTHFAZCQKGKEI-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[(4-pyrimidin-5-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=NC=NC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 ZMTHFAZCQKGKEI-UHFFFAOYSA-N 0.000 description 1
- BGLVUVHPTHMSFY-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[(4-tert-butylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C(C)(C)C)S(=O)(=O)C=2C=CC=CC=2)=C1 BGLVUVHPTHMSFY-UHFFFAOYSA-N 0.000 description 1
- MHKVDKIVAJHZLK-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[2-(3-chlorophenoxy)ethyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CCOC=2C=C(Cl)C=CC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 MHKVDKIVAJHZLK-UHFFFAOYSA-N 0.000 description 1
- HZDFYHDRIXNRBD-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2SC=CN=2)S(=O)(=O)C=2C=CC=CC=2)=C1 HZDFYHDRIXNRBD-UHFFFAOYSA-N 0.000 description 1
- XZMUKHKKWYDRNK-UHFFFAOYSA-N methyl 3-[3-[[benzenesulfonyl-[[4-(2-methylpropyl)phenyl]methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(CC(C)C)=CC=2)S(=O)(=O)C=2C=CC=CC=2)=C1 XZMUKHKKWYDRNK-UHFFFAOYSA-N 0.000 description 1
- FNGVSOLKKUURPU-UHFFFAOYSA-N methyl 3-[3-[[methylsulfonyl-[(4-phenoxyphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(OC=3C=CC=CC=3)=CC=2)S(C)(=O)=O)=C1 FNGVSOLKKUURPU-UHFFFAOYSA-N 0.000 description 1
- PRLMNRKFLSZGGR-UHFFFAOYSA-N methyl 3-[3-[[methylsulfonyl-[(4-phenylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=CC=CC=2)S(C)(=O)=O)=C1 PRLMNRKFLSZGGR-UHFFFAOYSA-N 0.000 description 1
- IYKHWZWWCRHZMW-UHFFFAOYSA-N methyl 3-[3-[[pyridin-2-ylsulfonyl-[(4-pyrimidin-2-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=CN=2)S(=O)(=O)C=2N=CC=CC=2)=C1 IYKHWZWWCRHZMW-UHFFFAOYSA-N 0.000 description 1
- LFWAMZKMYZVOPI-UHFFFAOYSA-N methyl 3-[3-[[pyridin-2-ylsulfonyl-[(4-pyrimidin-5-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=NC=NC=2)S(=O)(=O)C=2N=CC=CC=2)=C1 LFWAMZKMYZVOPI-UHFFFAOYSA-N 0.000 description 1
- ZTWACRJRBFVNJT-UHFFFAOYSA-N methyl 3-[3-[[pyridin-2-ylsulfonyl-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2SC=CN=2)S(=O)(=O)C=2N=CC=CC=2)=C1 ZTWACRJRBFVNJT-UHFFFAOYSA-N 0.000 description 1
- IODAJBNHNVEOQR-UHFFFAOYSA-N methyl 3-[3-[[pyridin-3-ylsulfonyl-[(4-pyrimidin-2-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=CN=2)S(=O)(=O)C=2C=NC=CC=2)=C1 IODAJBNHNVEOQR-UHFFFAOYSA-N 0.000 description 1
- NTERSEVPVGMIRX-UHFFFAOYSA-N methyl 3-[3-[[pyridin-3-ylsulfonyl-[(4-pyrimidin-5-ylphenyl)methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=NC=NC=2)S(=O)(=O)C=2C=NC=CC=2)=C1 NTERSEVPVGMIRX-UHFFFAOYSA-N 0.000 description 1
- PQLPMWSXKPCSCL-UHFFFAOYSA-N methyl 3-[3-[[pyridin-3-ylsulfonyl-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]methyl]phenyl]propanoate Chemical compound COC(=O)CCC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2SC=CN=2)S(=O)(=O)C=2C=NC=CC=2)=C1 PQLPMWSXKPCSCL-UHFFFAOYSA-N 0.000 description 1
- TZOQETCEZDRPGE-UHFFFAOYSA-N methyl 5-(3-aminopropyl)thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(CCCN)S1 TZOQETCEZDRPGE-UHFFFAOYSA-N 0.000 description 1
- NZROUZYCYKMAKP-UHFFFAOYSA-N methyl 5-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]thiophene-2-carboxylate Chemical compound COC(=O)C1=CC=C(CCCNC(=O)OC(C)(C)C)S1 NZROUZYCYKMAKP-UHFFFAOYSA-N 0.000 description 1
- HCTOHICLBBTYEV-UHFFFAOYSA-N methyl 5-[3-[3-(3-chlorophenyl)propyl-cyclopropylsulfonylamino]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN(S(=O)(=O)C1CC1)CCCC1=CC=CC(Cl)=C1 HCTOHICLBBTYEV-UHFFFAOYSA-N 0.000 description 1
- BPSVQNZACTWEOS-UHFFFAOYSA-N methyl 5-[3-[3-(3-chlorophenyl)propyl-pyridin-3-ylsulfonylamino]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCN(S(=O)(=O)C=1C=NC=CC=1)CCCC1=CC=CC(Cl)=C1 BPSVQNZACTWEOS-UHFFFAOYSA-N 0.000 description 1
- HWMUEORPNLJONC-UHFFFAOYSA-N methyl 5-[3-[3-(3-chlorophenyl)propylamino]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCNCCCC1=CC=CC(Cl)=C1 HWMUEORPNLJONC-UHFFFAOYSA-N 0.000 description 1
- DPRIXMCSFWFPFA-UHFFFAOYSA-N methyl 5-[3-[[4-(1,3-thiazol-2-yl)phenyl]methylamino]propyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC)=CC=C1CCCNCC1=CC=C(C=2SC=CN=2)C=C1 DPRIXMCSFWFPFA-UHFFFAOYSA-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
- JCVXJSAKQDBJGW-UHFFFAOYSA-N methyl 7-[(1-methylimidazol-4-yl)sulfonyl-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]heptanoate Chemical compound C=1N(C)C=NC=1S(=O)(=O)N(CCCCCCC(=O)OC)CC(C=C1)=CC=C1C1=NC=CS1 JCVXJSAKQDBJGW-UHFFFAOYSA-N 0.000 description 1
- GWTFPRQNWBUAAX-UHFFFAOYSA-N methyl 7-[(4-butylphenyl)methyl-pyridin-3-ylsulfonylamino]heptanoate Chemical compound C1=CC(CCCC)=CC=C1CN(CCCCCCC(=O)OC)S(=O)(=O)C1=CC=CN=C1 GWTFPRQNWBUAAX-UHFFFAOYSA-N 0.000 description 1
- NLIUUOAHSBKBCM-UHFFFAOYSA-N methyl 7-[(4-butylphenyl)methylamino]heptanoate Chemical compound CCCCC1=CC=C(CNCCCCCCC(=O)OC)C=C1 NLIUUOAHSBKBCM-UHFFFAOYSA-N 0.000 description 1
- POKVWSTVYOLAJZ-UHFFFAOYSA-N methyl 7-[(4-imidazol-1-ylphenyl)methyl-pyridin-2-ylsulfonylamino]heptanoate Chemical compound C=1C=CC=NC=1S(=O)(=O)N(CCCCCCC(=O)OC)CC(C=C1)=CC=C1N1C=CN=C1 POKVWSTVYOLAJZ-UHFFFAOYSA-N 0.000 description 1
- AFQNVGOHVMTQLN-UHFFFAOYSA-N methyl 7-[(4-pyrazin-2-ylphenyl)methyl-pyridin-3-ylsulfonylamino]heptanoate Chemical compound C=1C=CN=CC=1S(=O)(=O)N(CCCCCCC(=O)OC)CC(C=C1)=CC=C1C1=CN=CC=N1 AFQNVGOHVMTQLN-UHFFFAOYSA-N 0.000 description 1
- HSDXENFCOZWFDT-UHFFFAOYSA-N methyl 7-[(4-pyrazin-2-ylphenyl)methylamino]heptanoate Chemical compound C1=CC(CNCCCCCCC(=O)OC)=CC=C1C1=CN=CC=N1 HSDXENFCOZWFDT-UHFFFAOYSA-N 0.000 description 1
- IFZIRBLWZWBSTD-UHFFFAOYSA-N methyl 7-[(4-pyrazol-1-ylphenyl)methyl-pyridin-2-ylsulfonylamino]heptanoate Chemical compound C=1C=CC=NC=1S(=O)(=O)N(CCCCCCC(=O)OC)CC(C=C1)=CC=C1N1C=CC=N1 IFZIRBLWZWBSTD-UHFFFAOYSA-N 0.000 description 1
- CDJQODCGXFLFPE-UHFFFAOYSA-N methyl 7-[(4-pyrazol-1-ylphenyl)methyl-pyridin-3-ylsulfonylamino]heptanoate Chemical compound C=1C=CN=CC=1S(=O)(=O)N(CCCCCCC(=O)OC)CC(C=C1)=CC=C1N1C=CC=N1 CDJQODCGXFLFPE-UHFFFAOYSA-N 0.000 description 1
- YYHGSUNAZYBVIP-UHFFFAOYSA-N methyl 7-[(4-pyrimidin-2-ylphenyl)methylamino]heptanoate Chemical compound C1=CC(CNCCCCCCC(=O)OC)=CC=C1C1=NC=CC=N1 YYHGSUNAZYBVIP-UHFFFAOYSA-N 0.000 description 1
- GJJZJKYSPJLRMJ-UHFFFAOYSA-N methyl 7-[pyridin-2-ylsulfonyl-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]heptanoate Chemical compound C=1C=CC=NC=1S(=O)(=O)N(CCCCCCC(=O)OC)CC(C=C1)=CC=C1C1=NC=CS1 GJJZJKYSPJLRMJ-UHFFFAOYSA-N 0.000 description 1
- AITWCSMJELVGHS-UHFFFAOYSA-N methyl 7-[pyridin-3-ylsulfonyl-[(4-pyrimidin-2-ylphenyl)methyl]amino]heptanoate Chemical compound C=1C=CN=CC=1S(=O)(=O)N(CCCCCCC(=O)OC)CC(C=C1)=CC=C1C1=NC=CC=N1 AITWCSMJELVGHS-UHFFFAOYSA-N 0.000 description 1
- MVHBJBUFBYZJKV-UHFFFAOYSA-N methyl 7-[pyridin-3-ylsulfonyl-[[4-(1,3-thiazol-2-yl)phenyl]methyl]amino]heptanoate Chemical compound C=1C=CN=CC=1S(=O)(=O)N(CCCCCCC(=O)OC)CC(C=C1)=CC=C1C1=NC=CS1 MVHBJBUFBYZJKV-UHFFFAOYSA-N 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- OJVSEHLMRCLAFY-UHFFFAOYSA-N methyl propanoate;hydrochloride Chemical compound Cl.CCC(=O)OC OJVSEHLMRCLAFY-UHFFFAOYSA-N 0.000 description 1
- 230000001089 mineralizing effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- QWCLKHXWGCBJPQ-SKCUWOTOSA-N n-[(2r)-1-[(3ar)-3a-[(4-fluorophenyl)methyl]-2-methyl-3-oxo-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]-1-oxo-3-phenylmethoxypropan-2-yl]-2-amino-2-methylpropanamide Chemical compound C([C@@]12CN(CCC1=NN(C2=O)C)C(=O)[C@@H](COCC=1C=CC=CC=1)NC(=O)C(C)(C)N)C1=CC=C(F)C=C1 QWCLKHXWGCBJPQ-SKCUWOTOSA-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
- 230000000926 neurological effect Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
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- OZBUTHYZYDVNOZ-UHFFFAOYSA-N tert-butyl 2-[3-[[benzenesulfonyl-[(4-pyrimidin-2-ylphenyl)methyl]amino]methyl]phenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=CN=2)S(=O)(=O)C=2C=CC=CC=2)=C1 OZBUTHYZYDVNOZ-UHFFFAOYSA-N 0.000 description 1
- QPEBHYQPYSOIPG-UHFFFAOYSA-N tert-butyl 2-[3-[[pyridin-2-ylsulfonyl-[(4-pyrimidin-2-ylphenyl)methyl]amino]methyl]phenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2N=CC=CN=2)S(=O)(=O)C=2N=CC=CC=2)=C1 QPEBHYQPYSOIPG-UHFFFAOYSA-N 0.000 description 1
- JOGLNFQYQOHBRT-UHFFFAOYSA-N tert-butyl 2-[3-[[pyridin-3-ylsulfonyl-[(4-pyrimidin-5-ylphenyl)methyl]amino]methyl]phenoxy]acetate Chemical compound CC(C)(C)OC(=O)COC1=CC=CC(CN(CC=2C=CC(=CC=2)C=2C=NC=NC=2)S(=O)(=O)C=2C=NC=CC=2)=C1 JOGLNFQYQOHBRT-UHFFFAOYSA-N 0.000 description 1
- YVCTUNFJMZLQJW-UHFFFAOYSA-N tert-butyl 5-[3-(phenylmethoxycarbonylamino)prop-1-ynyl]thiophene-2-carboxylate Chemical compound S1C(C(=O)OC(C)(C)C)=CC=C1C#CCNC(=O)OCC1=CC=CC=C1 YVCTUNFJMZLQJW-UHFFFAOYSA-N 0.000 description 1
- HFPUIDDBBWKTNO-UHFFFAOYSA-N tert-butyl 5-bromothiophene-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=C(Br)S1 HFPUIDDBBWKTNO-UHFFFAOYSA-N 0.000 description 1
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- DSPYCWLYGXGJNJ-UHFFFAOYSA-N tert-butyl n-prop-2-ynylcarbamate Chemical compound CC(C)(C)OC(=O)NCC#C DSPYCWLYGXGJNJ-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229910021515 thallium hydroxide Inorganic materials 0.000 description 1
- QGYXCSSUHCHXHB-UHFFFAOYSA-M thallium(i) hydroxide Chemical compound [OH-].[Tl+] QGYXCSSUHCHXHB-UHFFFAOYSA-M 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 229950004815 tigestol Drugs 0.000 description 1
- 229940032666 tiludronate disodium Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960004167 toremifene citrate Drugs 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
- PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- UKRDPEFKFJNXQM-UHFFFAOYSA-N vinylsilane Chemical class [SiH3]C=C UKRDPEFKFJNXQM-UHFFFAOYSA-N 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/70—Sulfur atoms
- C07D213/71—Sulfur atoms to which a second hetero atom is attached
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
- C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/30—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/45—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups at least one of the singly-bound nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfonamides
- C07C311/46—Y being a hydrogen or a carbon atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
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- C07—ORGANIC CHEMISTRY
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- 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
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- 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
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- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
- C07D409/12—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 chain containing hetero atoms as chain links
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- 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
- C07D417/12—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 chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
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- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
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- Medicinal Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Rheumatology (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Furan Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
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US6172797P | 1997-10-10 | 1997-10-10 | |
PCT/IB1998/001540 WO1999019300A1 (fr) | 1997-10-10 | 1998-10-05 | Agonistes de la prostaglandine et leur utilisation pour le traitement des problemes osseux |
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NO20001754D0 NO20001754D0 (no) | 2000-04-05 |
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UA67754C2 (uk) | 1997-10-10 | 2004-07-15 | Пфайзер, Інк. | Агоністи простагландину, фармацевтична композиція на їх основі (варіанти), спосіб нарощення та збереження кісткової маси у хребетних та спосіб лікування (варіанти) |
EP1000619A3 (fr) * | 1998-06-23 | 2002-07-24 | Pfizer Products Inc. | Méthode de traitement du glaucome |
NZ513825A (en) | 1999-03-05 | 2001-09-28 | Procter & Gamble | C 16 unsaturated FP-selective prostaglandins analogs |
TWI262185B (en) * | 1999-10-01 | 2006-09-21 | Eisai Co Ltd | Carboxylic acid derivatives having anti-hyperglycemia and anti-hyperlipemia action, and pharmaceutical composition containing the derivatives |
PT1132086E (pt) | 2000-01-31 | 2006-09-29 | Pfizer Prod Inc | Utilizacao de agonistas selectivos para o receptor da prostaglandina (pge2) 4 (ep4) para o tratamento de falha renal aguda e cronica |
US20010056060A1 (en) * | 2000-02-07 | 2001-12-27 | Cameron Kimberly O. | Treatment of osteoporsis with EP2/EP4 receptor selective agonists |
US20020013294A1 (en) | 2000-03-31 | 2002-01-31 | Delong Mitchell Anthony | Cosmetic and pharmaceutical compositions and methods using 2-decarboxy-2-phosphinico derivatives |
US20020172693A1 (en) | 2000-03-31 | 2002-11-21 | Delong Michell Anthony | Compositions and methods for treating hair loss using non-naturally occurring prostaglandins |
AU2002365969A1 (en) * | 2001-11-20 | 2003-06-10 | Scott Bruder | Flowable osteogenic and chondrogenic compositions |
PL370914A1 (en) * | 2001-11-30 | 2005-06-13 | Pfizer Products Inc. | Pharmaceutical compositions and methods for administering ep2 receptor selective agonists |
HUP0402135A3 (en) * | 2001-11-30 | 2008-04-28 | Pfizer | Controlled release implant forming polymeric compositions of bone growth promoting compounds and process for their preparation |
KR20040077884A (ko) * | 2002-01-31 | 2004-09-07 | 화이자 프로덕츠 인코포레이티드 | (3-{〔(4-3급-뷰틸-벤질)-(피리딘-3-설폰일)-아미노〕-메틸}-페녹시)-아세트산의 대사산물 |
JP2005532291A (ja) | 2002-04-12 | 2005-10-27 | ファイザー株式会社 | 抗炎症薬および鎮痛薬としてのピラゾール化合物 |
US6822120B2 (en) | 2002-05-24 | 2004-11-23 | Pharmacia Corporation | Sulfone liver X-receptor modulators |
AU2003241601A1 (en) | 2002-05-24 | 2003-12-12 | Pharmacia Corporation | Anilino liver x-receptor modulators |
JP2006021998A (ja) * | 2002-07-18 | 2006-01-26 | Ono Pharmaceut Co Ltd | Ep2アゴニストを有効成分とする月経困難症治療剤 |
HUE029417T2 (en) | 2002-10-10 | 2017-02-28 | Ono Pharmaceutical Co | Microspheres containing ONO-1301 |
GB0302094D0 (en) | 2003-01-29 | 2003-02-26 | Pharmagene Lab Ltd | EP4 receptor antagonists |
MXPA05009398A (es) * | 2003-03-04 | 2005-12-05 | Pfizer Prod Inc | Uso de agonistas selectivos del receptor ep2 en tratamiento medico. |
EP2422814A1 (fr) | 2003-07-25 | 2012-02-29 | Ono Pharmaceutical Co., Ltd. | Remède pour maladies associées aux cartilages |
WO2005027931A1 (fr) * | 2003-09-19 | 2005-03-31 | Pfizer Products Inc. | Compositions pharmaceutiques et methodes de traitement consistant en des associations d'un derive de la 2-alkylidene-19-nor-vitamine d et d'un agoniste selectif de ep2 ou ep4 |
GB0324269D0 (en) | 2003-10-16 | 2003-11-19 | Pharmagene Lab Ltd | EP4 receptor antagonists |
US20050203086A1 (en) * | 2004-03-04 | 2005-09-15 | Pfizer Inc. | Methods of treatment using an EP2 selective receptor agonist |
CA2571482A1 (fr) * | 2004-06-21 | 2005-12-29 | Pharmacia & Upjohn Company Llc | Inhibiteurs de pyk2 pour la stimulation de la fonction de l'osteoblaste |
US7858650B2 (en) | 2004-10-22 | 2010-12-28 | Ono Pharmaceutical Co., Ltd. | Medicinal composition for inhalation |
EP1848430B1 (fr) | 2004-12-31 | 2017-08-02 | Dr. Reddy's Laboratories Ltd. | Nouveaux dérivés de benzylamine en tant qu'inhibiteurs de cetp |
US8604055B2 (en) | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
RU2420316C2 (ru) | 2005-06-03 | 2011-06-10 | Оно Фармасьютикал Ко., Лтд. | Агент для регенерации и/или защиты нервов |
US7915316B2 (en) | 2005-08-22 | 2011-03-29 | Allergan, Inc | Sulfonamides |
US7696235B2 (en) | 2005-08-29 | 2010-04-13 | Allergan, Inc. | EP2 receptor agonists for treating glaucoma |
CN101495452B (zh) * | 2006-07-28 | 2012-04-25 | 辉瑞产品公司 | Ep2激动剂 |
EA200970067A1 (ru) | 2006-07-28 | 2009-08-28 | Пфайзер Продактс Инк. | Агонисты ep2 |
EP2269611B1 (fr) | 2006-11-16 | 2016-03-23 | Gemmus Pharma Inc. | Agonistes EP2 et EP4 en tant qu'agents pour le traitement d'une infection virale par le virus de la grippe A |
EP2094839B1 (fr) * | 2006-12-08 | 2020-02-05 | University of Rochester | Expansion de cellules souches hématopoïétiques |
CA2696995C (fr) * | 2007-08-21 | 2017-11-21 | Senomyx, Inc. | Identification de recepteurs humains t2r sensibles aux composes amers qui provoquent le gout amer dans des compositions, et utilisation de ceux-ci dans des analyses d'identification de composes qui inhibent (bloquent) le gout amer dans des compositions et utilisation de celles-ci |
WO2009027803A2 (fr) * | 2007-08-29 | 2009-03-05 | Pfizer Products Inc. | Formes polymorphes d'acide libre d'acide acétique 3-(((4-tert-butyl-benzyl)-(pyridine-3-sulfonyl)-amino)-méthyl)- phénoxy) |
US20110046385A1 (en) * | 2007-08-29 | 2011-02-24 | Pfizer Products Inc. | Polymorphs Of Prostaglandin Agonists And Methods For Making The Same |
CA2697950A1 (fr) * | 2007-08-29 | 2009-03-05 | Pfizer Products Inc. | Formes polymorphes d'agonistes de prostaglandine et procedes de fabrication de celles-ci |
ES2718813T3 (es) | 2008-03-12 | 2019-07-04 | Ube Industries | Compuesto de ácido piridilaminoacético |
EP2149551A1 (fr) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | Dérivés de N-(indol-3-ylalkyl)-(hétéro)arylamide en tant que modulateurs du récepteur EP2 |
EP2149552A1 (fr) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma AG | Dérivés de benzamide 5,6 substitués en tant que modulateurs du récepteur EP2 |
EP2149554A1 (fr) | 2008-07-30 | 2010-02-03 | Bayer Schering Pharma Aktiengesellschaft | Indolylamides en tant que modulateurs du récepteur EP2 |
DK2415763T3 (en) | 2009-03-30 | 2016-03-07 | Ube Industries | A pharmaceutical composition for the treatment or prevention of glaucoma |
WO2010116270A1 (fr) | 2009-04-10 | 2010-10-14 | Pfizer Inc. | Agonistes de ep2/4 |
AU2010336248A1 (en) | 2009-12-25 | 2012-08-02 | Ube Industries, Ltd. | Aminopyridine compound |
EP3056198A2 (fr) | 2010-09-16 | 2016-08-17 | MSP Co., Ltd | Utilisation de composés permettant d'induire la différenciation de cellules souches mésenchymateuses en chondrocytes |
WO2013024358A2 (fr) | 2011-08-18 | 2013-02-21 | Dr. Reddy's Laboratories Ltd. | Composés amines hétérocycliques substitués comme inhibiteurs de la protéine de transfert d'ester cholesterylique (cetp) |
WO2013046045A1 (fr) | 2011-09-27 | 2013-04-04 | Dr. Reddy's Laboratories, Ltd. | Dérivés de 5 - benzylaminométhyl - 6 - aminopyrazolo [3, 4 -b] pyridine utiles comme inhibiteurs de la cholestéryl ester -transfer protéine (cetp) dans le traitement de l'athérosclérose |
US8772541B2 (en) * | 2011-12-15 | 2014-07-08 | University of Pittsburgh—of the Commonwealth System of Higher Education | Cannabinoid receptor 2 (CB2) inverse agonists and therapeutic potential for multiple myeloma and osteoporosis bone diseases |
US20150272874A1 (en) | 2012-10-29 | 2015-10-01 | Cardio Incorporated | Pulmonary disease-specific therapeutic agent |
MY176887A (en) | 2013-02-28 | 2020-08-25 | Takeda Pharmaceuticals Co | Method for producing sulfonyl chloride compound |
US9676720B2 (en) | 2013-03-28 | 2017-06-13 | Ube Industries, Ltd. | Substituted biaryl compound |
JP6449166B2 (ja) | 2013-10-15 | 2019-01-09 | 小野薬品工業株式会社 | 薬剤溶出性ステントグラフト |
JP2017206444A (ja) * | 2014-09-26 | 2017-11-24 | 宇部興産株式会社 | 置換フェニル化合物 |
CN114591227A (zh) * | 2021-12-28 | 2022-06-07 | 上海冬洋生物科技有限公司 | 一种ep2受体选择性的前列腺素e2激动剂的制备方法 |
Family Cites Families (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR897566A (fr) | 1942-08-28 | 1945-03-26 | Bopp & Reuther Gmbh | Machine à rotors |
US3442890A (en) | 1965-06-15 | 1969-05-06 | Mead Johnson & Co | Substituted 3-benzazocin-16-ones |
US3528961A (en) | 1966-08-16 | 1970-09-15 | Allied Chem | Monoazo dyes from e-caprolactam |
US3780095A (en) | 1970-04-08 | 1973-12-18 | Byk Gulden Lomberg Chem Fab | Acylated anilino-carboxylic acids and their salts |
US3987091A (en) | 1973-04-12 | 1976-10-19 | Merck & Co., Inc. | 11,12-secoprostaglandins |
US4033996A (en) | 1973-04-25 | 1977-07-05 | Merck & Co., Inc. | 8-Aza-9-oxo(and dioxo)-thia-11,12-secoprostaglandins |
JPS5019756A (fr) | 1973-06-25 | 1975-03-01 | ||
SE7414770L (fr) | 1973-12-13 | 1975-06-16 | Merck & Co Inc | |
DK366475A (da) | 1974-08-30 | 1976-03-01 | Merck & Co Inc | Fremgangsmade til fremstilling af aryloxy- eller arylthioholdige secoprostaglandiner |
US4055596A (en) | 1974-09-13 | 1977-10-25 | Merck & Co., Inc. | 11,12-Seco-prostaglandins |
US3991106A (en) | 1974-09-13 | 1976-11-09 | Merck & Co., Inc. | 16-Ethers of 8-aza-9-dioxothia-11,12-seco-prostaglandins |
US4175203A (en) | 1976-12-17 | 1979-11-20 | Merck & Co., Inc. | Interphenylene 11,12-secoprostaglandins |
US4112236A (en) | 1977-04-04 | 1978-09-05 | Merck & Co., Inc. | Interphenylene 8-aza-9-dioxothia-11,12-secoprostaglandins |
US4097601A (en) | 1977-08-26 | 1978-06-27 | Pfizer Inc. | Bone deposition by 2-descarboxy-2-(tetrazol-5-yl)-11-dexosy-16-aryl prostaglandins |
US4243678A (en) | 1977-12-30 | 1981-01-06 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Acylhydrocarbylaminoalkanoic acids, compositions and uses |
DE3000377A1 (de) | 1980-01-07 | 1981-07-09 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue sulfonamide, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel |
DE3042482A1 (de) | 1980-11-11 | 1982-06-24 | A. Nattermann & Cie GmbH, 5000 Köln | N-benzoyl- (omega) -anilinoalkancarbonsaeuren, -salze und -ester, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
CA1214170A (fr) | 1981-06-16 | 1986-11-18 | Patrick Choay | Procedes de preparation de nouveaux composes du type arylbenzenesulfonamide |
FI832935A (fi) | 1982-08-20 | 1984-02-21 | Midit | Derivat av w-aminosyror, deras framstaellning samt dessa derivat innehaollande blandningar |
DE3719046A1 (de) | 1987-06-06 | 1988-12-15 | Basf Ag | Verwendung von salzen von sulfonamidcarbonsaeuren als korrosionsinhibitoren in waessrigen systemen |
US5084466A (en) * | 1989-01-31 | 1992-01-28 | Hoffmann-La Roche Inc. | Novel carboxamide pyridine compounds which have useful pharmaceutical utility |
US5081152A (en) | 1989-07-05 | 1992-01-14 | Kotobuki Seiyaku Co., Ltd. | Azulene derivatives as thromboxane a2 and prostaglandin endoperoxide receptor antagonist |
JPH0467105A (ja) * | 1990-07-09 | 1992-03-03 | Nippon Telegr & Teleph Corp <Ntt> | 偏波保持光ファイバ |
GB9110722D0 (en) * | 1991-05-17 | 1991-07-10 | Fujisawa Pharmaceutical Co | Amine derivatives |
GB9116732D0 (en) * | 1991-08-02 | 1991-09-18 | Fujisawa Pharmaceutical Co | Indole derivatives |
CA2113787A1 (fr) * | 1993-01-29 | 1994-07-30 | Nobuyuki Hamanaka | Sulfonamides carbocycliques |
HN1996000101A (es) * | 1996-02-28 | 1997-06-26 | Inc Pfizer | Terapia combinada para la osteoporosis |
DE19648793A1 (de) | 1996-11-26 | 1998-05-28 | Basf Ag | Neue Benzamide und deren Anwendung |
UA59384C2 (uk) * | 1996-12-20 | 2003-09-15 | Пфайзер, Інк. | Похідні сульфонамідів та амідів як агоністи простагландину, фармацевтична композиція та способи лікування на їх основі |
AUPO440696A0 (en) * | 1996-12-30 | 1997-01-23 | Fujisawa Pharmaceutical Co., Ltd. | New use |
UA67754C2 (uk) | 1997-10-10 | 2004-07-15 | Пфайзер, Інк. | Агоністи простагландину, фармацевтична композиція на їх основі (варіанти), спосіб нарощення та збереження кісткової маси у хребетних та спосіб лікування (варіанти) |
PL370914A1 (en) * | 2001-11-30 | 2005-06-13 | Pfizer Products Inc. | Pharmaceutical compositions and methods for administering ep2 receptor selective agonists |
KR20040077884A (ko) * | 2002-01-31 | 2004-09-07 | 화이자 프로덕츠 인코포레이티드 | (3-{〔(4-3급-뷰틸-벤질)-(피리딘-3-설폰일)-아미노〕-메틸}-페녹시)-아세트산의 대사산물 |
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