CA1193603A - Sulfonylureas, processes for their preparation, pharmaceutical formulations based on these compounds and their use - Google Patents
Sulfonylureas, processes for their preparation, pharmaceutical formulations based on these compounds and their useInfo
- Publication number
- CA1193603A CA1193603A CA000410586A CA410586A CA1193603A CA 1193603 A CA1193603 A CA 1193603A CA 000410586 A CA000410586 A CA 000410586A CA 410586 A CA410586 A CA 410586A CA 1193603 A CA1193603 A CA 1193603A
- Authority
- CA
- Canada
- Prior art keywords
- dihydro
- methyl
- carboxamido
- benzenesulfonyl
- oxoquinoline
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims abstract description 40
- 150000001875 compounds Chemical class 0.000 title claims abstract description 25
- 229940100389 Sulfonylurea Drugs 0.000 title claims abstract description 13
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims abstract description 3
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 3
- 239000000460 chlorine Substances 0.000 claims abstract description 3
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 30
- -1 benzenesulfonyl halide Chemical class 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000000047 product Substances 0.000 claims description 7
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 5
- GHDLZGOOOLEJKI-UHFFFAOYSA-N benzenesulfonylurea Chemical compound NC(=O)NS(=O)(=O)C1=CC=CC=C1 GHDLZGOOOLEJKI-UHFFFAOYSA-N 0.000 claims description 5
- 239000004202 carbamide Substances 0.000 claims description 5
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 claims description 5
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 5
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 5
- 150000003672 ureas Chemical class 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- ALZKZGUTVJXYEF-UHFFFAOYSA-N benzenesulfonylcarbamic acid Chemical group OC(=O)NS(=O)(=O)C1=CC=CC=C1 ALZKZGUTVJXYEF-UHFFFAOYSA-N 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 3
- 229940101209 mercuric oxide Drugs 0.000 claims description 3
- 159000000000 sodium salts Chemical class 0.000 claims description 3
- 229940124530 sulfonamide Drugs 0.000 claims description 3
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 150000004657 carbamic acid derivatives Chemical group 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 150000003455 sulfinic acids Chemical class 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 4
- ZAKHBTUHOCVBCG-UHFFFAOYSA-N n-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-1-methyl-2-oxoquinoline-3-carboxamide Chemical compound O=C1N(C)C2=CC=CC=C2C=C1C(=O)NCCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 ZAKHBTUHOCVBCG-UHFFFAOYSA-N 0.000 claims 3
- JIDGHNUSLKTCLO-UHFFFAOYSA-N 1-methyl-2-oxo-n-[2-(4-sulfamoylphenyl)ethyl]quinoline-3-carboxamide Chemical compound O=C1N(C)C2=CC=CC=C2C=C1C(=O)NCCC1=CC=C(S(N)(=O)=O)C=C1 JIDGHNUSLKTCLO-UHFFFAOYSA-N 0.000 claims 2
- WEJKEHFBBCNLBG-UHFFFAOYSA-N N-[2-[4-(cyclohexylcarbamothioylsulfamoyl)phenyl]ethyl]-1-methyl-2-oxoquinoline-3-carboxamide Chemical compound CN1C(C(=CC2=CC=CC=C12)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=S)NC1CCCCC1)=O WEJKEHFBBCNLBG-UHFFFAOYSA-N 0.000 claims 1
- 150000008064 anhydrides Chemical class 0.000 claims 1
- PVMBGVAQRSHDBB-UHFFFAOYSA-N benzenesulfonylthiourea Chemical group NC(=S)NS(=O)(=O)C1=CC=CC=C1 PVMBGVAQRSHDBB-UHFFFAOYSA-N 0.000 claims 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims 1
- 239000008280 blood Substances 0.000 abstract description 7
- 210000004369 blood Anatomy 0.000 abstract description 7
- 230000002218 hypoglycaemic effect Effects 0.000 abstract description 5
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 3
- 238000002844 melting Methods 0.000 description 26
- 230000008018 melting Effects 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 239000000203 mixture Substances 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 9
- 229960004756 ethanol Drugs 0.000 description 8
- QAXZWHGWYSJAEI-UHFFFAOYSA-N n,n-dimethylformamide;ethanol Chemical compound CCO.CN(C)C=O QAXZWHGWYSJAEI-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-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
- 235000013877 carbamide Nutrition 0.000 description 6
- 238000001816 cooling Methods 0.000 description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 4
- 125000005518 carboxamido group Chemical group 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 239000012948 isocyanate Substances 0.000 description 4
- 150000002513 isocyanates Chemical class 0.000 description 4
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 4
- 229940093932 potassium hydroxide Drugs 0.000 description 4
- 235000011118 potassium hydroxide Nutrition 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- ANGBCBQEOGTPLW-UHFFFAOYSA-N 1,6-dimethyl-2-oxoquinoline-3-carboxylic acid Chemical compound CN1C(=O)C(C(O)=O)=CC2=CC(C)=CC=C21 ANGBCBQEOGTPLW-UHFFFAOYSA-N 0.000 description 2
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical class C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 description 2
- FXNSVEQMUYPYJS-UHFFFAOYSA-N 4-(2-aminoethyl)benzenesulfonamide Chemical compound NCCC1=CC=C(S(N)(=O)=O)C=C1 FXNSVEQMUYPYJS-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229940022682 acetone Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 229940112021 centrally acting muscle relaxants carbamic acid ester Drugs 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000008164 mustard oil Substances 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 150000003585 thioureas Chemical class 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- DFNCYDFCUVAFDG-UHFFFAOYSA-N 1-methyl-2-oxoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C=C(C(O)=O)C(=O)N(C)C2=C1 DFNCYDFCUVAFDG-UHFFFAOYSA-N 0.000 description 1
- COFKONCDRIZNFW-UHFFFAOYSA-N 2-[(5-chloro-2-nitrophenyl)methylidene]propanedioic acid Chemical compound OC(=O)C(C(O)=O)=CC1=CC(Cl)=CC=C1[N+]([O-])=O COFKONCDRIZNFW-UHFFFAOYSA-N 0.000 description 1
- PXYMACAYRGWCDC-UHFFFAOYSA-N 5-cyclohexyl-1h-imidazole-2-carboxamide Chemical class N1C(C(=O)N)=NC(C2CCCCC2)=C1 PXYMACAYRGWCDC-UHFFFAOYSA-N 0.000 description 1
- OKAWLYLDHRITNN-UHFFFAOYSA-N 6-chloro-1-methylquinolin-2-one Chemical compound C1=C(Cl)C=C2C=CC(=O)N(C)C2=C1 OKAWLYLDHRITNN-UHFFFAOYSA-N 0.000 description 1
- XCWIXLMCHFBXLT-UHFFFAOYSA-N 6-chloro-2-oxo-1h-quinoline-3-carboxylic acid Chemical compound ClC1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XCWIXLMCHFBXLT-UHFFFAOYSA-N 0.000 description 1
- SNGUSPTUOBIBRV-UHFFFAOYSA-N 6-methyl-2-oxo-1h-quinoline-3-carboxylic acid Chemical compound N1C(=O)C(C(O)=O)=CC2=CC(C)=CC=C21 SNGUSPTUOBIBRV-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical class NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229910020676 Co—N Inorganic materials 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 150000008331 benzenesulfonamides Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001714 carbamic acid halides Chemical class 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- ZYKZKUHYPCWHSS-UHFFFAOYSA-N cyclohexen-1-ylurea Chemical compound NC(=O)NC1=CCCCC1 ZYKZKUHYPCWHSS-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- JUVJQIPDVWOVNP-UHFFFAOYSA-N hexylurea Chemical compound CCCCCCNC(N)=O JUVJQIPDVWOVNP-UHFFFAOYSA-N 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 229960001330 hydroxycarbamide Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AFCCDDWKHLHPDF-UHFFFAOYSA-M metam-sodium Chemical class [Na+].CNC([S-])=S AFCCDDWKHLHPDF-UHFFFAOYSA-M 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006476 reductive cyclization reaction Methods 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VNMLVHLVBFHHSN-UHFFFAOYSA-N thiophen-2-ylcarbamic acid Chemical class OC(=O)NC1=CC=CS1 VNMLVHLVBFHHSN-UHFFFAOYSA-N 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Quinoline Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813134780 DE3134780A1 (de) | 1981-09-02 | 1981-09-02 | "sulfonylharnstoffe, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen und ihre verwendung" |
| DEP3134780.0 | 1981-09-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1193603A true CA1193603A (en) | 1985-09-17 |
Family
ID=6140704
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000410586A Expired CA1193603A (en) | 1981-09-02 | 1982-09-01 | Sulfonylureas, processes for their preparation, pharmaceutical formulations based on these compounds and their use |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US4542139A (https=) |
| EP (1) | EP0073507B1 (https=) |
| JP (1) | JPS5846068A (https=) |
| KR (1) | KR880002706B1 (https=) |
| AT (1) | ATE16102T1 (https=) |
| AU (1) | AU558339B2 (https=) |
| CA (1) | CA1193603A (https=) |
| DE (2) | DE3134780A1 (https=) |
| DK (1) | DK391982A (https=) |
| ES (6) | ES8306113A1 (https=) |
| FI (1) | FI76567C (https=) |
| GR (1) | GR76895B (https=) |
| HU (1) | HU188805B (https=) |
| IL (1) | IL66697A0 (https=) |
| MX (1) | MX154808A (https=) |
| NO (1) | NO822940L (https=) |
| NZ (1) | NZ201768A (https=) |
| PH (1) | PH18218A (https=) |
| PT (1) | PT75492B (https=) |
| ZA (1) | ZA826391B (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3210063A1 (de) * | 1982-03-19 | 1983-09-22 | Hoechst Ag, 6230 Frankfurt | Sulfonylharnstoffe, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen und ihre verwendung |
| SE9201076L (sv) * | 1992-04-06 | 1993-10-07 | Shimon Slavin | Användningen av gamla läkemedel för behandling av diabetes |
| US5681832A (en) * | 1995-02-17 | 1997-10-28 | The United States Of America As Represented By The Department Of Health And Human Services | Aroylaniline compounds, pharmaceutical compositions, and methods of using same to inhibit viral activity |
| JP2000256323A (ja) * | 1999-01-08 | 2000-09-19 | Japan Tobacco Inc | ２−オキソキノリン化合物及びその医薬用途 |
| ES2330719T3 (es) * | 2000-12-28 | 2009-12-15 | SHIONOGI & CO., LTD. | Derivados de 2-piridona con afinidad para el receptor cannabinoide de tipo 2. |
| KR101423483B1 (ko) * | 2005-11-03 | 2014-07-28 | 포톨라 파마슈티컬스, 인코포레이티드 | 〔４-(６-할로-７-치환된-２,４-디옥소-１,４-디히드로-２ｈ-퀴나졸린-３-일)-페닐〕-５-클로로티오펜-２-일-설포닐우레아 및 이의 형태 및 이와 관련된 방법 |
| BRPI0810800A2 (pt) * | 2007-05-02 | 2014-10-29 | Portola Pharm Inc | Sais de [4-(6-fluoro-7-metilamino-2,4-dioxo-1, 4-diidro-2h-quinazolin-3-il)-fenil]-5-cloro-tiofen-2-il-s ulfonilureia, formas e métodos relacionados a eles. |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3819633A (en) * | 1970-04-01 | 1974-06-25 | Erba Carlo Spa | (iso)quinolyl sulfonylureas having antidiabetic activity |
| DE2621958A1 (de) * | 1976-05-18 | 1977-12-08 | Hoechst Ag | Benzolsulfonylharnstoffe und verfahren zu ihrer herstellung |
| AT357560B (de) * | 1976-05-18 | 1980-07-25 | Hoechst Ag | Verfahren zur herstellung von neuen (1,2- dihydro-2-oxo-nicotinamido)-alkylbenzolsul- fonylharnstoffen und von deren salzen |
| MTP848B (en) * | 1978-06-27 | 1980-06-24 | Hoechst Ag | Sulfonyl ureas process for their manufacture pharmaceutical preparation on the basis of there compounds and their use |
| DE2948434A1 (de) * | 1979-12-01 | 1981-06-11 | Hoechst Ag, 6000 Frankfurt | 1-piperidinsulfonylharnstoffe und verfahren zu ihrer herstellung |
| DE2951135A1 (de) * | 1979-12-19 | 1981-06-25 | Hoechst Ag, 6230 Frankfurt | Sulfonylharnstoffe, verfahren zu ihrer herstellung, pharmazeutische praeparate auf basis dieser verbindungen und ihre verwendung |
-
1981
- 1981-09-02 DE DE19813134780 patent/DE3134780A1/de not_active Withdrawn
-
1982
- 1982-08-28 AT AT82107938T patent/ATE16102T1/de not_active IP Right Cessation
- 1982-08-28 EP EP82107938A patent/EP0073507B1/de not_active Expired
- 1982-08-28 DE DE8282107938T patent/DE3266953D1/de not_active Expired
- 1982-08-31 MX MX7875A patent/MX154808A/es unknown
- 1982-08-31 ES ES515384A patent/ES8306113A1/es not_active Expired
- 1982-08-31 PH PH27799A patent/PH18218A/en unknown
- 1982-08-31 ES ES515396A patent/ES8306115A1/es not_active Expired
- 1982-08-31 ES ES515399A patent/ES515399A0/es active Granted
- 1982-08-31 NZ NZ201768A patent/NZ201768A/en unknown
- 1982-08-31 ES ES515395A patent/ES515395A0/es active Granted
- 1982-08-31 ES ES515397A patent/ES515397A0/es active Granted
- 1982-08-31 NO NO822940A patent/NO822940L/no unknown
- 1982-08-31 GR GR69173A patent/GR76895B/el unknown
- 1982-08-31 KR KR8203918A patent/KR880002706B1/ko not_active Expired
- 1982-08-31 ES ES515398A patent/ES515398A0/es active Granted
- 1982-08-31 FI FI823007A patent/FI76567C/fi not_active IP Right Cessation
- 1982-09-01 JP JP57150810A patent/JPS5846068A/ja active Pending
- 1982-09-01 IL IL66697A patent/IL66697A0/xx unknown
- 1982-09-01 ZA ZA826391A patent/ZA826391B/xx unknown
- 1982-09-01 DK DK391982A patent/DK391982A/da not_active Application Discontinuation
- 1982-09-01 HU HU822814A patent/HU188805B/hu unknown
- 1982-09-01 CA CA000410586A patent/CA1193603A/en not_active Expired
- 1982-09-01 AU AU87892/82A patent/AU558339B2/en not_active Ceased
- 1982-09-01 PT PT75492A patent/PT75492B/pt unknown
-
1984
- 1984-04-26 US US06/603,987 patent/US4542139A/en not_active Expired - Fee Related
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |