AU758566B2 - Method of using cyclooxygenase-2 inhibitors in maintaining the fetal ductus ateriosus during treatment and prevention of preterm labor - Google Patents
Method of using cyclooxygenase-2 inhibitors in maintaining the fetal ductus ateriosus during treatment and prevention of preterm labor Download PDFInfo
- Publication number
- AU758566B2 AU758566B2 AU11926/99A AU1192699A AU758566B2 AU 758566 B2 AU758566 B2 AU 758566B2 AU 11926/99 A AU11926/99 A AU 11926/99A AU 1192699 A AU1192699 A AU 1192699A AU 758566 B2 AU758566 B2 AU 758566B2
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- benzenesulfonamide
- radicals
- pyrazol
- trifluoromethyl
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims description 52
- 208000006399 Premature Obstetric Labor Diseases 0.000 title claims description 35
- 238000011282 treatment Methods 0.000 title claims description 30
- 230000001605 fetal effect Effects 0.000 title claims description 10
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 title description 25
- 230000002265 prevention Effects 0.000 title description 16
- -1 cyano, carboxyl Chemical group 0.000 claims description 226
- 150000001875 compounds Chemical class 0.000 claims description 56
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 33
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 29
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000001188 haloalkyl group Chemical group 0.000 claims description 22
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 21
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 20
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000004414 alkyl thio group Chemical group 0.000 claims description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 10
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- 125000001145 hydrido group Chemical group *[H] 0.000 claims description 10
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 9
- 210000003017 ductus arteriosus Anatomy 0.000 claims description 9
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- 125000002971 oxazolyl group Chemical group 0.000 claims description 9
- 125000003342 alkenyl group Chemical group 0.000 claims description 8
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 8
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 5
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 239000004305 biphenyl Substances 0.000 claims description 5
- 235000010290 biphenyl Nutrition 0.000 claims description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000006343 heptafluoro propyl group Chemical group 0.000 claims description 5
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 5
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 5
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 4
- 125000006003 dichloroethyl group Chemical group 0.000 claims description 4
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 3
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 3
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 3
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 3
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 2
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000004470 heterocyclooxy group Chemical group 0.000 claims description 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- FOPWYBMDYRFLEB-UHFFFAOYSA-N 2-[5-(3,4-difluorophenyl)-2-(trifluoromethyl)-1,3-oxazol-4-yl]benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C1=C(C=2C=C(F)C(F)=CC=2)OC(C(F)(F)F)=N1 FOPWYBMDYRFLEB-UHFFFAOYSA-N 0.000 claims 1
- RBIMSEGCQFORTH-UHFFFAOYSA-N 4-(2-methyl-4-phenyl-1,3-oxazol-5-yl)benzenesulfonamide Chemical compound O1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=C(S(N)(=O)=O)C=C1 RBIMSEGCQFORTH-UHFFFAOYSA-N 0.000 claims 1
- INRQTVDUZFESAO-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-3-(4-methylsulfonylphenyl)-2h-furan-5-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=C(F)C(F)=CC=2)C(=O)OC1 INRQTVDUZFESAO-UHFFFAOYSA-N 0.000 claims 1
- ZVSGOCRXDUNISM-UHFFFAOYSA-N 4-[5-(2-hydroxyethyl)-3-phenyl-1,2-oxazol-4-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1C1=C(CCO)ON=C1C1=CC=CC=C1 ZVSGOCRXDUNISM-UHFFFAOYSA-N 0.000 claims 1
- NSQNZEUFHPTJME-UHFFFAOYSA-N 4-[5-(4-chlorophenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(C(F)(F)F)=N1 NSQNZEUFHPTJME-UHFFFAOYSA-N 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims 1
- 150000003254 radicals Chemical class 0.000 description 72
- 125000004432 carbon atom Chemical group C* 0.000 description 29
- 239000002585 base Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 13
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 13
- 208000037805 labour Diseases 0.000 description 13
- 229940093444 Cyclooxygenase 2 inhibitor Drugs 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 125000004430 oxygen atom Chemical group O* 0.000 description 9
- 125000004434 sulfur atom Chemical group 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 description 8
- 150000002460 imidazoles Chemical class 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 8
- 150000003180 prostaglandins Chemical class 0.000 description 8
- 229910052717 sulfur Inorganic materials 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 7
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical class O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- 150000005840 aryl radicals Chemical class 0.000 description 6
- 125000005594 diketone group Chemical group 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 210000003754 fetus Anatomy 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- 230000035935 pregnancy Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 244000028419 Styrax benzoin Species 0.000 description 4
- 235000000126 Styrax benzoin Nutrition 0.000 description 4
- 235000008411 Sumatra benzointree Nutrition 0.000 description 4
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
- 229960002130 benzoin Drugs 0.000 description 4
- 229940111134 coxibs Drugs 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
- 235000019382 gum benzoic Nutrition 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 150000003217 pyrazoles Chemical class 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 229940125712 tocolytic agent Drugs 0.000 description 4
- 239000003675 tocolytic agent Substances 0.000 description 4
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 108010037464 Cyclooxygenase 1 Proteins 0.000 description 3
- 239000012425 OXONE® Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
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- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 3
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- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
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- 125000001246 bromo group Chemical group Br* 0.000 description 3
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- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000008774 maternal effect Effects 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
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- 239000011780 sodium chloride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 230000003195 tocolytic effect Effects 0.000 description 3
- LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 3
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 2
- 229930182837 (R)-adrenaline Natural products 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- BMUKKTUHUDJSNZ-UHFFFAOYSA-N 4-[1-hydroxy-2-(1-phenoxypropan-2-ylamino)propyl]phenol Chemical compound C=1C=C(O)C=CC=1C(O)C(C)NC(C)COC1=CC=CC=C1 BMUKKTUHUDJSNZ-UHFFFAOYSA-N 0.000 description 2
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
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- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/06—Anti-spasmodics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6388997P | 1997-10-31 | 1997-10-31 | |
| US60/063889 | 1997-10-31 | ||
| PCT/US1998/022246 WO1999022720A2 (en) | 1997-10-31 | 1998-10-27 | Selective cyclooxygenase-2 inhibitors against premature labor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU1192699A AU1192699A (en) | 1999-05-24 |
| AU758566B2 true AU758566B2 (en) | 2003-03-27 |
Family
ID=22052179
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU11926/99A Ceased AU758566B2 (en) | 1997-10-31 | 1998-10-27 | Method of using cyclooxygenase-2 inhibitors in maintaining the fetal ductus ateriosus during treatment and prevention of preterm labor |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1027048A2 (enExample) |
| JP (1) | JP2001521889A (enExample) |
| AR (1) | AR014000A1 (enExample) |
| AU (1) | AU758566B2 (enExample) |
| BR (1) | BR9813164A (enExample) |
| CA (1) | CA2308639A1 (enExample) |
| TW (2) | TW200404535A (enExample) |
| WO (1) | WO1999022720A2 (enExample) |
| ZA (1) | ZA989876B (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1617716A (zh) * | 2000-06-08 | 2005-05-18 | 德克萨斯系统大学评议会 | 杂环衍生物与使用方法 |
| ES2275218T3 (es) | 2003-05-07 | 2007-06-01 | Osteologix A/S | Sales de estroncio hidrosolubles para el tratamiento de afecciones de cartilagos y/o huesos. |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994026731A1 (en) * | 1993-05-13 | 1994-11-24 | Merck Frosst Canada Inc. | 2-substituted-3,4-diarylthiophene derivatives as inhibitors of cyclooxygenase |
| WO1995000501A2 (en) * | 1993-06-24 | 1995-01-05 | Merck Frosst Canada Inc. | Phenyl heterocycles as cyclooxygenase-2 inhibitors |
| WO1997031631A1 (en) * | 1996-02-27 | 1997-09-04 | Rpms Technology Limited | Cox-2 selective inhibitors for managing labour and uterine contractions |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5466823A (en) * | 1993-11-30 | 1995-11-14 | G.D. Searle & Co. | Substituted pyrazolyl benzenesulfonamides |
| US5677318A (en) * | 1996-07-11 | 1997-10-14 | Merck Frosst Canada, Inc. | Diphenyl-1,2-3-thiadiazoles as anti-inflammatory agents |
-
1998
- 1998-10-27 JP JP2000518654A patent/JP2001521889A/ja not_active Withdrawn
- 1998-10-27 EP EP98955026A patent/EP1027048A2/en not_active Ceased
- 1998-10-27 BR BR9813164-8A patent/BR9813164A/pt not_active Application Discontinuation
- 1998-10-27 WO PCT/US1998/022246 patent/WO1999022720A2/en not_active Ceased
- 1998-10-27 CA CA002308639A patent/CA2308639A1/en not_active Abandoned
- 1998-10-27 AU AU11926/99A patent/AU758566B2/en not_active Ceased
- 1998-10-29 ZA ZA9809876A patent/ZA989876B/xx unknown
- 1998-10-30 TW TW092134686A patent/TW200404535A/zh unknown
- 1998-10-30 TW TW087118094A patent/TW577739B/zh not_active IP Right Cessation
- 1998-10-30 AR ARP980105483A patent/AR014000A1/es not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994026731A1 (en) * | 1993-05-13 | 1994-11-24 | Merck Frosst Canada Inc. | 2-substituted-3,4-diarylthiophene derivatives as inhibitors of cyclooxygenase |
| WO1995000501A2 (en) * | 1993-06-24 | 1995-01-05 | Merck Frosst Canada Inc. | Phenyl heterocycles as cyclooxygenase-2 inhibitors |
| WO1997031631A1 (en) * | 1996-02-27 | 1997-09-04 | Rpms Technology Limited | Cox-2 selective inhibitors for managing labour and uterine contractions |
Also Published As
| Publication number | Publication date |
|---|---|
| TW577739B (en) | 2004-03-01 |
| EP1027048A2 (en) | 2000-08-16 |
| JP2001521889A (ja) | 2001-11-13 |
| AU1192699A (en) | 1999-05-24 |
| WO1999022720A2 (en) | 1999-05-14 |
| WO1999022720A3 (en) | 1999-08-26 |
| AR014000A1 (es) | 2001-01-31 |
| TW200404535A (en) | 2004-04-01 |
| CA2308639A1 (en) | 1999-05-14 |
| ZA989876B (en) | 1999-10-29 |
| BR9813164A (pt) | 2000-08-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGA | Letters patent sealed or granted (standard patent) |