JPH06100525A - Oxamide-containing sulfonanilide compound - Google Patents
Oxamide-containing sulfonanilide compoundInfo
- Publication number
- JPH06100525A JPH06100525A JP4251725A JP25172592A JPH06100525A JP H06100525 A JPH06100525 A JP H06100525A JP 4251725 A JP4251725 A JP 4251725A JP 25172592 A JP25172592 A JP 25172592A JP H06100525 A JPH06100525 A JP H06100525A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- group
- formula
- carbon atoms
- reacting
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 38
- YIKSCQDJHCMVMK-UHFFFAOYSA-N Oxamide Chemical compound NC(=O)C(N)=O YIKSCQDJHCMVMK-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- -1 cycloalkyl alcohol Chemical compound 0.000 abstract description 19
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 abstract description 11
- 150000001412 amines Chemical class 0.000 abstract description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 abstract description 5
- 230000000202 analgesic effect Effects 0.000 abstract description 5
- 230000000802 nitrating effect Effects 0.000 abstract description 5
- 230000003266 anti-allergic effect Effects 0.000 abstract description 4
- 230000001754 anti-pyretic effect Effects 0.000 abstract description 4
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 3
- 239000002221 antipyretic Substances 0.000 abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- KJVBJICWGQIMOZ-UHFFFAOYSA-N 2-fluoro-5-nitroaniline Chemical compound NC1=CC([N+]([O-])=O)=CC=C1F KJVBJICWGQIMOZ-UHFFFAOYSA-N 0.000 abstract description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 abstract description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 2
- 230000007774 longterm Effects 0.000 abstract 1
- 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 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-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
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
- UDWKPLLNAQEMPI-UHFFFAOYSA-N n-(2-fluoro-5-nitrophenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC([N+]([O-])=O)=CC=C1F UDWKPLLNAQEMPI-UHFFFAOYSA-N 0.000 description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 239000000043 antiallergic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 2
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 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 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- NVWRBCDYXGZLAT-UHFFFAOYSA-N n-(2-cyclohexyloxy-5-nitrophenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC([N+]([O-])=O)=CC=C1OC1CCCCC1 NVWRBCDYXGZLAT-UHFFFAOYSA-N 0.000 description 2
- QUBXPWBAQDXJIV-UHFFFAOYSA-N n-(5-amino-2-cyclohexyloxyphenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(N)=CC=C1OC1CCCCC1 QUBXPWBAQDXJIV-UHFFFAOYSA-N 0.000 description 2
- IGRAVAFHBHAIRV-UHFFFAOYSA-N n-(5-amino-2-phenoxyphenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(N)=CC=C1OC1=CC=CC=C1 IGRAVAFHBHAIRV-UHFFFAOYSA-N 0.000 description 2
- FUBBAWCFVISWIE-UHFFFAOYSA-N n-(5-nitro-2-phenoxyphenyl)methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC([N+]([O-])=O)=CC=C1OC1=CC=CC=C1 FUBBAWCFVISWIE-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
- 229910000105 potassium hydride Inorganic materials 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 2
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- XGLVDUUYFKXKPL-UHFFFAOYSA-N 2-(2-methoxyethoxy)-n,n-bis[2-(2-methoxyethoxy)ethyl]ethanamine Chemical compound COCCOCCN(CCOCCOC)CCOCCOC XGLVDUUYFKXKPL-UHFFFAOYSA-N 0.000 description 1
- FCAJYRVEBULFKS-UHFFFAOYSA-N 2-(oxolan-2-yl)ethanol Chemical compound OCCC1CCCO1 FCAJYRVEBULFKS-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- WJYIASZWHGOTOU-UHFFFAOYSA-N Heptylamine Chemical compound CCCCCCCN WJYIASZWHGOTOU-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- JYENLFHVUQDQQB-UHFFFAOYSA-M N.[Na+].[SH-].Cl Chemical compound N.[Na+].[SH-].Cl JYENLFHVUQDQQB-UHFFFAOYSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910006069 SO3H Inorganic materials 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 239000003907 antipyretic analgesic agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- QXNDZONIWRINJR-UHFFFAOYSA-N azocane Chemical compound C1CCCNCCC1 QXNDZONIWRINJR-UHFFFAOYSA-N 0.000 description 1
- CHQVQXZFZHACQQ-UHFFFAOYSA-M benzyl(triethyl)azanium;bromide Chemical compound [Br-].CC[N+](CC)(CC)CC1=CC=CC=C1 CHQVQXZFZHACQQ-UHFFFAOYSA-M 0.000 description 1
- SXGBREZGMJVYRL-UHFFFAOYSA-N butan-1-amine;hydrobromide Chemical compound [Br-].CCCC[NH3+] SXGBREZGMJVYRL-UHFFFAOYSA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 150000003983 crown ethers Chemical class 0.000 description 1
- KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- HSOHBWMXECKEKV-UHFFFAOYSA-N cyclooctanamine Chemical compound NC1CCCCCCC1 HSOHBWMXECKEKV-UHFFFAOYSA-N 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- MVFCKEFYUDZOCX-UHFFFAOYSA-N iron(2+);dinitrate Chemical compound [Fe+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O MVFCKEFYUDZOCX-UHFFFAOYSA-N 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- QHDUJTCUPWHNPK-UHFFFAOYSA-N methyl 7-methoxy-2h-indazole-3-carboxylate Chemical compound COC1=CC=CC2=C(C(=O)OC)NN=C21 QHDUJTCUPWHNPK-UHFFFAOYSA-N 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、抗炎症作用、解熱作
用、鎮痛作用および抗アレルギー作用を有するオキサミ
ドを有するスルホンアニリド化合物に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sulfoneanilide compound having an oxamide having anti-inflammatory action, antipyretic action, analgesic action and antiallergic action.
【従来の技術】スルホンアニリド化合物は種々の化合物
が知られており、５位にアミノ基を有するスルホンアニ
リド化合物としては、米国特許第３，８５６，８５９号
明細書に記載の化合物が知られているが、本発明のオキ
サミドを有するスルホンアニリド化合物は知られていな
い。Various compounds are known as sulfone anilide compounds, and as the sulfone anilide compound having an amino group at the 5-position, compounds described in US Pat. No. 3,856,859 are known. However, the sulfonanilide compound having an oxamide of the present invention is not known.
【発明が解決しようとする課題】しかしながら、前記の
５位にアミノ基を有するスルホンアニリド化合物は薬効
が十分でなかった。However, the above-mentioned sulfonanilide compound having an amino group at the 5-position is not sufficiently effective.
【０００２】本発明の目的は、抗炎症作用、解熱作用、
鎮痛作用および抗アレルギー作用を有する優れた化合物
を提供することにある。The purpose of the present invention is to have anti-inflammatory action, antipyretic action,
It is to provide an excellent compound having an analgesic action and an antiallergic action.
【課題を解決するための手段】本発明者らは、上記課題
の解決を目的に鋭意検討した結果、下記に表されるオキ
サミドを有するスルホンアニリド化合物が目的を達成で
きることを見い出し、本発明を完成した。As a result of intensive studies aimed at solving the above-mentioned problems, the present inventors have found that the sulfonanilide compound having an oxamide shown below can achieve the purpose, and completed the present invention. did.
【０００３】すなわち、本発明は、式That is, the present invention uses the formula
【０００４】 [0004]
【０００５】（式中、Ｒ1は炭素原子数１〜３個のアル
キル基であり、Ｒ2はフェニル基または炭素原子数５〜
７個のシクロアルキル基であり、Ｒ3は水素原子または
炭素原子数１〜４個のアルキル基であり、Ｒ4は炭素原
子数１〜８個のアルキル基、炭素原子数３〜８個のシク
ロアルキル基、炭素原子数４〜６個のシクロアルキルメ
チル基、炭素原子数３〜５個のアルケニル基、炭素原子
数２〜４個のヒドロキシアルキル基またはベンジル基で
あるか、Ｒ3とＲ4が一緒になって５〜９員環の複素環を
示す。）で表わされるオキサミドを有するスルホンアニ
リド化合物である。(In the formula, R 1 is an alkyl group having 1 to 3 carbon atoms, and R 2 is a phenyl group or 5 to 5 carbon atoms.
7 cycloalkyl groups, R 3 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R 4 is an alkyl group having 1 to 8 carbon atoms, 3 to 8 carbon atoms A cycloalkyl group, a cycloalkylmethyl group having 4 to 6 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, a hydroxyalkyl group having 2 to 4 carbon atoms or a benzyl group, or R 3 and R 4 together represents a 5- to 9-membered heterocycle. ) Is a sulfone anilide compound having an oxamide.
【０００６】本発明において、Ｒ1の炭素原子数１〜３
個のアルキル基とは、メチル基、エチル基、ｎ−プロピ
ル基である。Ｒ2の炭素原子数５〜７個のシクロアルキ
ル基とは、シクロペンチル基、シクロヘキシル基、シク
ロヘプチル基である。Ｒ3の炭素原子数１〜４個のアル
キル基とは、メチル基、エチル基、ｎ−プロピル基、イ
ソプロピル基、ｎ−ブチル基、イソブチル基、ｔ−ブチ
ル基である。Ｒ4の炭素原子数１〜８個のアルキル基と
は、直鎖状または分枝鎖状のアルキル基であり、例えば
メチル基、エチル基、ｎ−プロピル基、イソプロピル
基、ｎ−ブチル基、イソブチル基、ｔ−ブチル基、ｎ−
ペンチル基、２−メチルブチル基、３−メチルブチル
基、ｎ−ヘキシル基、３−メチルペンチル基、４−メチ
ルペンチル基、２−エチルブチル基、ｎ−ヘプチル基、
ｎ−オクチル基などである。Ｒ4の炭素原子数３〜８個
のシクロアルキル基とは、シクロプロピル基、シクロブ
チル基、シクロペンチル基、シクロヘキシル基、シクロ
ヘプチル基、シクロオクチル基である。Ｒ4の炭素原子
数４〜６個のシクロアルキルメチル基とは、シクロプロ
ピルメチル基、シクロブチルメチル基、シクロペンチル
メチル基である。Ｒ4の炭素原子数３〜５個のアルケニ
ル基とは、直鎖状または分枝鎖状のアルケニル基であ
り、例えばアリル基、２−ブテニル基、３−メチル−２
−ブテニル基などである。Ｒ4の炭素原子数２〜４個の
ヒドロキシアルキル基とは、例えば２−ヒドロキシエチ
ル基、３−ヒドロキシプロピル基、２，３−ジヒドロキ
シプロピル基などである。Ｒ3とＲ4が一緒になって形成
する５〜９員環の複素環とは、例えばピロリジノ基、ピ
ペリジノ基、ヘキサメチレンイミノ基、ヘプタメチレン
イミノ基、オクタメチレンイミノ基、モルホリノ基、チ
オモルホリノ基、ピペラジノ基、４−メチルピペラジノ
基、４−ジフェニルメチルピペラジノ基である。塩とは
ナトリウム、カリウムなどとのアルカリ金属塩、カルシ
ウム、マグネシウムなどとのアルカリ土類金属塩、アン
モニウム塩およびメチルアミン、エチルアミン、ブチル
アミン、ジメチルアミン、ジエチルアミン、トリエチル
アミン、トリブチルアミン、エタノールアミン、ピリジ
ン、リジン、アルギニンなどの有機塩基との塩である。In the present invention, R1 has 1 to 3 carbon atoms.
The alkyl group is a methyl group, an ethyl group, or an n-propyl group. The cycloalkyl group having 5 to 7 carbon atoms of R 2 is a cyclopentyl group, a cyclohexyl group or a cycloheptyl group. The alkyl group having 1 to 4 carbon atoms of R 3 is a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group or a t-butyl group. The alkyl group having 1 to 8 carbon atoms of R 4 is a linear or branched alkyl group, and examples thereof include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, Isobutyl group, t-butyl group, n-
Pentyl group, 2-methylbutyl group, 3-methylbutyl group, n-hexyl group, 3-methylpentyl group, 4-methylpentyl group, 2-ethylbutyl group, n-heptyl group,
An n-octyl group and the like. The cycloalkyl group having 3 to 8 carbon atoms for R 4 is a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, or a cyclooctyl group. The cycloalkylmethyl group having 4 to 6 carbon atoms represented by R 4 is a cyclopropylmethyl group, a cyclobutylmethyl group or a cyclopentylmethyl group. The alkenyl group having 3 to 5 carbon atoms of R 4 is a linear or branched alkenyl group, for example, an allyl group, 2-butenyl group, 3-methyl-2.
A butenyl group and the like. The hydroxyalkyl group having 2 to 4 carbon atoms for R 4 is, for example, a 2-hydroxyethyl group, a 3-hydroxypropyl group, a 2,3-dihydroxypropyl group or the like. The 5- to 9-membered heterocycle formed by R 3 and R 4 together includes, for example, a pyrrolidino group, a piperidino group, a hexamethyleneimino group, a heptamethyleneimino group, an octamethyleneimino group, a morpholino group and a thiomorpholino group. Group, piperazino group, 4-methylpiperazino group, and 4-diphenylmethylpiperazino group. With salts, alkali metal salts with sodium, potassium, etc., alkaline earth metal salts with calcium, magnesium, etc., ammonium salts and methylamine, ethylamine, butylamine, dimethylamine, diethylamine, triethylamine, tributylamine, ethanolamine, pyridine, It is a salt with organic bases such as lysine and arginine.
【０００７】本発明の式（Ｉ）の化合物は、例えば下記
に示す（ａ）〜（ｆ）の製造工程により得ることができ
る。The compound of formula (I) of the present invention can be obtained, for example, by the production steps (a) to (f) shown below.
【０００８】（ａ）まず、２−フルオロ−５−ニトロア
ニリンに、 式 Ｒ1−ＳＯ3Ｈ （ＩＩ） （式中、Ｒ1は前記と同意義である。）で表されるスル
ホン酸またはその反応性誘導体（例えば、酸ハロゲン化
物、酸無水物など）を反応させることにより、(A) First, 2-fluoro-5-nitroa
Nirin, the formula R1-SO3H (II) (wherein R1Is as defined above. ) Represented by
Fonic acid or its reactive derivatives (eg acid halogenated
Substance, acid anhydride, etc.)
【０００９】式 Expression
【００１０】で表される化合物を得ることができる。A compound represented by can be obtained.
【００１１】本反応において式（ＩＩ）で表されるスル
ホン酸を使用する場合には、Ｎ，Ｎ’−ジシクロヘキシ
ルカルボジイミドなどの縮合剤の存在下に行うのが好ま
しい。また、反応性誘導体を使用する場合には塩基存在
下で行うのが好ましく、塩基としては水酸化リチウム、
水酸化ナトリウム、水酸化カリウム、炭酸ナトリウム、
炭酸カリウム、炭酸水素ナトリウム、炭酸水素カリウム
などの無機塩基またはトリエチルアミン、トリ−ｎ−ブ
チルアミン、１，５−ジアザビシクロ［４．３．０］−
５−ノネン、１，８−ジアザビシクロ［５．４．０］−
７−ウンデセン、４−メチルモルホリン、１−メチルピ
ペリジン、ピリジン、Ｎ，Ｎ−ジメチルアミノピリジン
などの有機塩基が挙げられる。When the sulfonic acid represented by the formula (II) is used in this reaction, it is preferably carried out in the presence of a condensing agent such as N, N'-dicyclohexylcarbodiimide. Further, when using a reactive derivative, it is preferably carried out in the presence of a base, as the base lithium hydroxide,
Sodium hydroxide, potassium hydroxide, sodium carbonate,
Inorganic bases such as potassium carbonate, sodium hydrogen carbonate, and potassium hydrogen carbonate or triethylamine, tri-n-butylamine, 1,5-diazabicyclo [4.3.0]-
5-nonene, 1,8-diazabicyclo [5.4.0]-
Organic bases such as 7-undecene, 4-methylmorpholine, 1-methylpiperidine, pyridine, N, N-dimethylaminopyridine and the like can be mentioned.
【００１２】本反応は、通常溶媒中で行われ、溶媒とし
てはジクロロメタン、クロロホルム、酢酸エチル、ジオ
キサン、テトラヒドロフラン、エチルエーテル、ベンゼ
ン、トルエン、キシレン、アセトン、アセトニトリル、
水、ピリジン、Ｎ，Ｎ−ジメチルホルムアミド、ジメチ
ルスルホキシドなどが挙げられる。This reaction is usually carried out in a solvent, and as the solvent, dichloromethane, chloroform, ethyl acetate, dioxane, tetrahydrofuran, ethyl ether, benzene, toluene, xylene, acetone, acetonitrile,
Water, pyridine, N, N-dimethylformamide, dimethylsulfoxide and the like can be mentioned.
【００１３】（ｂ）次に、式（ＩＩＩ）の化合物にフェ
ノールまたは炭素原子数５〜７個のシクロアルキルアル
コールを塩基存在下、反応させることにより、式(B) Next, by reacting the compound of formula (III) with phenol or a cycloalkyl alcohol having 5 to 7 carbon atoms in the presence of a base,
【００１４】 [0014]
【００１５】（式中、Ｒ1およびＲ2は前記と同意義であ
る。）で表される化合物を得ることができる。A compound represented by the formula (wherein R 1 and R 2 are as defined above) can be obtained.
【００１６】本反応における塩基としては水酸化リチウ
ム、水酸化ナトリウム、水酸化カリウムなどのアルカリ
金属水酸化物、炭酸ナトリウム、炭酸カリウムなどのア
ルカリ金属炭酸塩、炭酸水素ナトリウム、炭酸水素カリ
ウムなどのアルカリ金属炭酸水素塩、水素化ナトリウ
ム、水素化カリウムなどのアルカリ金属水素化物、金属
ナトリウム、ナトリウムアミドなどの無機塩基またはト
リエチルアミン、トリ−ｎ−ブチルアミン、１，５−ジ
アザビシクロ［４．３．０］−５−ノネン、１，８−ジ
アザビシクロ［５．４．０］−７−ウンデセン、ピリジ
ン、Ｎ，Ｎ−ジメチルアミノピリジンなどの有機塩基な
どが挙げられる。Examples of the base in this reaction include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metals such as sodium hydrogen carbonate and potassium hydrogen carbonate. Alkali metal hydrides such as metal hydrogen carbonate, sodium hydride and potassium hydride, inorganic bases such as metal sodium and sodium amide, or triethylamine, tri-n-butylamine, 1,5-diazabicyclo [4.3.0]- Examples thereof include organic bases such as 5-nonene, 1,8-diazabicyclo [5.4.0] -7-undecene, pyridine, and N, N-dimethylaminopyridine.
【００１７】本反応は、無溶媒またはジオキサン、テト
ラヒドロフラン、エチルエーテル、石油エーテル、ｎ−
ヘキサン、シクロヘキサン、ベンゼン、トルエン、キシ
レン、ピリジン、Ｎ，Ｎ−ジメチルホルムアミド、ジメ
チルスルホキシド、ジクロロメタン、クロロホルム、水
などの溶媒を任意に選択して行うことができる。This reaction is solvent-free or dioxane, tetrahydrofuran, ethyl ether, petroleum ether, n-
A solvent such as hexane, cyclohexane, benzene, toluene, xylene, pyridine, N, N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform, and water can be arbitrarily selected and used.
【００１８】本反応においては、ヨウ化カリウム、トリ
ス［２−（２−メトキシエトキシ）エチル］アミン、テ
トラ−ｎ−ブチルアンモニウムクロリド、テトラ−ｎ−
ブチルアンモニウムブロミド、ベンジルトリエチルアン
モニウムクロリド、ベンジルトリエチルアンモニウムブ
ロミド、トリカプチルメチルアンモニウムクロリドなど
の４級アンモニウム塩、１８−クラウン−６ エーテル
などのクラウンエーテルなどを加えることにより反応を
加速することもできる。In this reaction, potassium iodide, tris [2- (2-methoxyethoxy) ethyl] amine, tetra-n-butylammonium chloride, tetra-n-
The reaction can also be accelerated by adding a quaternary ammonium salt such as butylammonium bromide, benzyltriethylammonium chloride, benzyltriethylammonium bromide, tricaptylmethylammonium chloride, or a crown ether such as 18-crown-6 ether.
【００１９】（ｃ）次いで、式（ＩＶ）の化合物のニト
ロ基を還元することにより、式(C) The nitro group of the compound of formula (IV) is then reduced to give a compound of formula
【００２０】 [0020]
【００２１】（式中、Ｒ1およびＲ2は前記と同意義であ
る。）で表される化合物を得ることができる。A compound represented by the formula (wherein R 1 and R 2 have the same meanings as described above) can be obtained.
【００２２】還元はニトロ基を還元してアミノ基とする
通常の還元方法でよく、例えばパラジウム−炭素、ラネ
ーニッケル、白金などを触媒として用いる接触還元、鉄
や錫を用いる還元、硫化ナトリウム−塩化アンモニウム
を用いる還元、水素化ホウ素ナトリウム、水素化リチウ
ムアルミニウムなどを用いる還元などが挙げられる。The reduction may be carried out by a conventional reduction method in which a nitro group is reduced to an amino group. For example, catalytic reduction using palladium-carbon, Raney nickel, platinum, etc. as a catalyst, reduction using iron or tin, sodium sulfide-ammonium chloride. And reduction using sodium borohydride, lithium aluminum hydride and the like.
【００２３】本反応に用いる溶媒としては、還元方法に
より任意に選択すればよく、一般的にはメタノール、エ
タノール、ｎ−プロパノールなどのアルコール、水、酢
酸、酢酸エチル、ジオキサン、テトラヒドロフラン、ア
セトニトリルなどが挙げられる。The solvent used in this reaction may be arbitrarily selected according to the reduction method, and generally, alcohols such as methanol, ethanol and n-propanol, water, acetic acid, ethyl acetate, dioxane, tetrahydrofuran, acetonitrile and the like are used. Can be mentioned.
【００２４】（ｄ）次いで、式（Ｖ）の化合物と式 Ｃｌ−ＣＯＣＯ2−Ｒ5 （ＶＩ） （式中、Ｒ5は直鎖状または分子鎖状の炭素原子数１〜
５個のアルキル基である。）で表される化合物を反応さ
せることにより、式(D) Next, the compound of the formula (V) and the formula Cl-COCO 2 -R 5 (VI) (wherein R 5 is a linear or molecular chain having 1 to 10 carbon atoms).
5 alkyl groups. ) By reacting a compound represented by the formula
【００２５】 [0025]
【００２６】（式中、Ｒ1、Ｒ2およびＲ5は前記と同意
義である。）で表される化合物を得ることができる。A compound represented by the formula (wherein R 1 , R 2 and R 5 have the same meanings as described above) can be obtained.
【００２７】本反応は塩基存在化に行うのが好ましく、
塩基としては水酸化リチウム、水酸化ナトリウム、水酸
化カリウムなどのアルカリ金属水酸化物、炭酸ナトリウ
ム、炭酸カリウムなどのアルカリ金属炭酸塩、炭酸水素
ナトリウム、炭酸水素カリウムなどのアルカリ金属炭酸
水素塩、水素化ナトリウム、水素化カリウムなどのアル
カリ金属水素化物、金属ナトリウム、ナトリウムアミド
などの無機塩基またはトリエチルアミン、トリ−ｎ−ブ
チルアミン、１，５−ジアザビシクロ［４．３．０］−
５−ノネン、１，８−ジアザビシクロ［５．４．０］−
７−ウンデセン、ピリジン、Ｎ，Ｎ−ジメチルアミノピ
リジンなどの有機塩基などが挙げられる。This reaction is preferably carried out in the presence of a base,
Examples of the base include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate, and hydrogen. Alkali metal hydrides such as sodium hydride and potassium hydride, inorganic bases such as sodium metal and sodium amide, or triethylamine, tri-n-butylamine, 1,5-diazabicyclo [4.3.0]-
5-nonene, 1,8-diazabicyclo [5.4.0]-
Organic bases such as 7-undecene, pyridine, N, N-dimethylaminopyridine and the like can be mentioned.
【００２８】本反応は、無溶媒またはジオキサン、テト
ラヒドロフラン、エチルエーテル、石油エーテル、ｎ−
ヘキサン、シクロヘキサン、ベンゼン、トルエン、キシ
レン、クロロベンゼン、ピリジン、酢酸エチル、アセト
ニトリル、Ｎ，Ｎ−ジメチルホルムアミド、ジメチルス
ルホキシド、ジクロロメタン、クロロホルム、水などの
溶媒を任意に選択して行うことができる。This reaction is solvent-free or dioxane, tetrahydrofuran, ethyl ether, petroleum ether, n-
Solvents such as hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, ethyl acetate, acetonitrile, N, N-dimethylformamide, dimethylsulfoxide, dichloromethane, chloroform and water can be arbitrarily selected and used.
【００２９】（ｅ）次いで、式（ＶＩＩ）の化合物を硝
酸または硝酸塩などのニトロ化剤を用いてニトロ化する
ことにより、式(E) Then, by nitrating the compound of formula (VII) with a nitrating agent such as nitric acid or a nitrate, the compound of formula
【００３０】 [0030]
【００３１】（式中、Ｒ1、Ｒ2およびＲ5は前記と同意
義である。）で表される化合物を得ることができる。A compound represented by the formula (wherein R 1 , R 2 and R 5 are as defined above) can be obtained.
【００３２】ニトロ化反応における硝酸塩としては硝酸
ナトリウム、硝酸カリウム、硝酸鉄、硝酸ウレアなどを
用いることができ、使用する溶媒としてはニトロ化剤に
応じて任意に選択するのが好ましく、酢酸、無水酢酸、
トリフルオロ酢酸、硫酸、ジクロロメタン、クロロホル
ム、ベンゼン、ジオキサン、エタノールなどが挙げられ
る。As the nitrate in the nitration reaction, sodium nitrate, potassium nitrate, iron nitrate, urea nitrate and the like can be used, and the solvent to be used is preferably selected arbitrarily according to the nitrating agent, and acetic acid or acetic anhydride is used. ,
Examples include trifluoroacetic acid, sulfuric acid, dichloromethane, chloroform, benzene, dioxane, ethanol and the like.
【００３３】（ｆ）最後に式（ＶＩＩＩ）の化合物と式(F) Finally, the compound of formula (VIII) and the formula
【００３４】 [0034]
【００３５】（式中、Ｒ3およびＲ4は前記と同意義であ
る。）で表されるアミン類と反応させることにより、本
発明の式（Ｉ）の化合物を得ることができる。The compound of formula (I) of the present invention can be obtained by reacting with an amine represented by the formula (wherein R 3 and R 4 are as defined above).
【００３６】本反応は、無溶媒または溶媒中で、室温か
ら無溶媒の場合にはアミン類の沸点の範囲、また、溶媒
を使用する場合には溶媒の沸点の範囲の温度条件下で式
（ＩＸ）で表されるアミン類と反応させることができ
る。This reaction is carried out without solvent or in a solvent under the temperature conditions of room temperature to the boiling point of amines in the case of no solvent, and the boiling point of solvent in the case of using a solvent. It can be reacted with amines represented by IX).
【００３７】本反応で使用する溶媒としては、水、メタ
ノール、エタノール、プロパノール、ｔ−ブタノール、
ジエチルエーテル、テトラヒドロフラン、ジオキサン、
アセトン、アセトニトリル、ベンゼン、トルエン、キシ
レン、クロロベンゼン、Ｎ，Ｎ−ジメチルホルムアミ
ド、ジメチルスルホキシドなどが挙げられる。As the solvent used in this reaction, water, methanol, ethanol, propanol, t-butanol,
Diethyl ether, tetrahydrofuran, dioxane,
Acetone, acetonitrile, benzene, toluene, xylene, chlorobenzene, N, N-dimethylformamide, dimethyl sulfoxide and the like can be mentioned.
【００３８】本発明の化合物は、経口または非経口的に
慣用の投与剤型で投与することができる。これらは、例
えば錠剤、粉剤、顆粒剤、散剤、カプセル剤、液剤、乳
剤、懸濁剤、注射剤などであり、いずれも通常の方法に
より製造することができる。人に対して抗炎症剤、解熱
剤、鎮痛剤および抗アレルギー剤として用いる場合、そ
の投与量は、年齢、体重、症状、投与経路、投与回数な
どによって異なるが、通常１日当り５〜１０００ｍｇで
ある。The compounds of the present invention can be administered orally or parenterally in conventional dosage forms. These include, for example, tablets, powders, granules, powders, capsules, solutions, emulsions, suspensions, injections and the like, all of which can be manufactured by a usual method. When used as an anti-inflammatory agent, antipyretic agent, analgesic agent and antiallergic agent for humans, the dose is usually 5 to 1000 mg per day, although it varies depending on age, weight, symptoms, administration route, number of administrations and the like.
【発明の効果】本発明の化合物は、抗炎症作用、解熱作
用、鎮痛作用、抗アレルギー作用などを示し、消化管障
害などの副作用が少ないため抗炎症剤、解熱剤、鎮痛剤
および抗アレルギー剤として有用である。INDUSTRIAL APPLICABILITY The compound of the present invention exhibits anti-inflammatory action, antipyretic action, analgesic action, antiallergic action and the like, and since it has few side effects such as digestive tract disorders, it is used as an antiinflammatory drug, antipyretic drug, analgesic and antiallergic agent. It is useful.
【実施例】次に、実施例を挙げ本発明を更に詳細に説明
する。 実施例１ （１）２−フルオロ−５−ニトロアニリン５２．１ｇを
含むピリジン３３４ｍｌ溶液に、氷冷下、メタンスルホ
ニルクロリド４２．１ｇを加え、室温で７時間攪拌し
た。反応液に水を加え、析出物を瀘取後、粗結晶をエタ
ノールで再結晶して淡黄色針状晶のＮ−（２−フルオロ
−５−ニトロフェニル）メタンスルホンアミド５６．９
ｇを得た。EXAMPLES Next, the present invention will be described in more detail with reference to examples. Example 1 (1) To a 334 ml solution of pyridine containing 52.1 g of 2-fluoro-5-nitroaniline, 42.1 g of methanesulfonyl chloride was added under ice cooling, and the mixture was stirred at room temperature for 7 hours. Water was added to the reaction solution, the precipitate was filtered, and the crude crystals were recrystallized from ethanol to give pale yellow needle crystals of N- (2-fluoro-5-nitrophenyl) methanesulfonamide 56.9.
g was obtained.
【００３９】ｍ．ｐ．１２８〜１２９℃M. p. 128-129 ° C
【００４０】（２）フェノール７３．５ｇおよび水酸化
ナトリウム３１．２ｇを含む２５０ｍｌ水溶液に、Ｎ−
（２−フルオロ−５−ニトロフェニル）メタンスルホン
アミド５０．０ｇを加え、５時間還流後、反応液を氷冷
し、撹拌下、３６％塩酸５０ｍｌ、エタノール２００ｍ
ｌを順に加えた。析出物を瀘取後、エタノール、水の順
で洗浄し、風乾して黄色プリズム晶のＮ−（５−ニトロ
−２−フェノキシフェニル）メタンスルホンアミド５
２．２ｇを得た。(2) To a 250 ml aqueous solution containing 73.5 g of phenol and 31.2 g of sodium hydroxide, N-
(2-Fluoro-5-nitrophenyl) methanesulfonamide (50.0 g) was added and the mixture was refluxed for 5 hours. The reaction mixture was ice-cooled, 36% hydrochloric acid (50 ml) and ethanol (200 m) were stirred.
1 were added in order. The precipitate was filtered, washed with ethanol and water in this order, and air-dried to give yellow prism crystals of N- (5-nitro-2-phenoxyphenyl) methanesulfonamide 5
2.2 g was obtained.
【００４１】ｍ．ｐ．１１２〜１１３．５℃M. p. 112-113.5 ° C
【００４２】（３）Ｎ−（５−ニトロ−２−フェノキシ
フェニル）メタンスルホンアミド５２．１ｇに塩化アン
モニウム２．７ｇを含む５１ｍｌ水溶液を加え、８０℃
に加熱撹拌下、鉄粉４２．５ｇを加え、２時間撹拌し
た。反応物を５０℃まで冷却後、酢酸エチルおよび水を
加え、酢酸エチルで抽出した。有機層を水、飽和食塩水
の順で洗浄後、無水硫酸マグネシウムで乾燥した。溶媒
を留去後、残渣をエタノールで再結晶してＮ−（５−ア
ミノ−２−フェノキシフェニル）メタンスルホンアミド
２９．６ｇを得た。(3) A 51 ml aqueous solution containing 2.7 g of ammonium chloride was added to 52.1 g of N- (5-nitro-2-phenoxyphenyl) methanesulfonamide, and the mixture was heated to 80 ° C.
With heating and stirring, 42.5 g of iron powder was added to the above and stirred for 2 hours. The reaction mixture was cooled to 50 ° C, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine in this order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was recrystallized from ethanol to obtain 29.6 g of N- (5-amino-2-phenoxyphenyl) methanesulfonamide.
【００４３】ｍ．ｐ．１１１．５〜１１３．５℃M. p. 111.5-113.5 ° C
【００４４】（４）Ｎ−（５−アミノ−２−フェノキシ
フェニル）メタンスルホンアミド１０．４ｇおよびピリ
ジン３．３ｇを含むジクロロメタン６５ｍｌ溶液に、氷
冷却下、エチルオキサリルクロリド５．６ｇを加え、
１．５間撹拌した。反応液に水を加え、ジクロロメタン
で抽出後、有機層を水、３規定塩酸、飽和食塩水の順で
洗浄し、無水硫酸マグネシウムで乾燥した。溶媒を留去
後、残渣をエタノールで再結晶して、無色結晶のＮ−
（５−エチルオキサリルアミノ−２−フェノキシフェニ
ル）メタンスルホンアミド１１．９ｇを得た。(4) To a solution of 65 g of dichloromethane containing 10.4 g of N- (5-amino-2-phenoxyphenyl) methanesulfonamide and 3.3 g of pyridine was added 5.6 g of ethyloxalyl chloride under ice cooling,
Stir for 1.5 minutes. Water was added to the reaction solution and the mixture was extracted with dichloromethane. The organic layer was washed with water, 3N hydrochloric acid and saturated brine in that order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was recrystallized from ethanol to give colorless crystals of N-
11.9 g of (5-ethyloxalylamino-2-phenoxyphenyl) methanesulfonamide was obtained.
【００４５】ｍ．ｐ．１４０．５〜１４２．５℃M. p. 140.5-142.5 ° C
【００４６】（５）Ｎ−（５−エチルオキサリルアミノ
−２−フェノキシフェニル）メタンスルホンアミド１
１．８ｇを含む酢酸３１ｍｌ溶液に、１１０℃で加熱攪
拌下、６０％硝酸３．５ｇを加え、３０分間攪拌した。
反応液を室温に戻し、水を加え、析出物を瀘取後、エタ
ノール−ｎ−ヘキサンで再結晶して黄色針状晶のＮ−
（５−エチルオキサリルアミノ−４−ニトロ−２−フェ
ノキシフェニル）メタンスルホンアミド８．６ｇを得
た。(5) N- (5-ethyloxalylamino-2-phenoxyphenyl) methanesulfonamide 1
To 31 ml of acetic acid solution containing 1.8 g, 3.5 g of 60% nitric acid was added with heating and stirring at 110 ° C., and the mixture was stirred for 30 minutes.
The reaction solution was returned to room temperature, water was added, the precipitate was filtered, and then recrystallized from ethanol-n-hexane to obtain yellow needle crystals of N-.
8.6 g of (5-ethyloxalylamino-4-nitro-2-phenoxyphenyl) methanesulfonamide was obtained.
【００４７】ｍ．ｐ．１９４．５〜１９５．５℃M. p. 194.5-195.5 ° C
【００４８】（６）Ｎ−（５−エチルオキサリルアミノ
−４−ニトロ−２−フェノキシフェニル）メタンスルホ
ンアミド１．５ｇを含むテトラヒドロフラン３．５ｍｌ
溶液に室温でｎ−ペンチルアミン０．９３ｇを加え、１
間撹拌した。反応液に３規定塩酸を加え中和し、析出物
を濾取後、テトラヒドロフラン−エタノールで再結晶し
て、黄色針状晶のＮ−［４−ニトロ−５−（ｎ−ペンチ
ルアミノオキサリルアミノ）−２−フェノキシフェニ
ル］メタンスルホンアミド１．１ｇを得た。(6) 3.5 ml of tetrahydrofuran containing 1.5 g of N- (5-ethyloxalylamino-4-nitro-2-phenoxyphenyl) methanesulfonamide
0.93 g of n-pentylamine was added to the solution at room temperature, and 1
It was stirred for a while. The reaction mixture was neutralized with 3N hydrochloric acid, and the precipitate was collected by filtration and recrystallized from tetrahydrofuran-ethanol to give yellow needle crystals of N- [4-nitro-5- (n-pentylaminooxalylamino). 1.1 g of 2-phenoxyphenyl] methanesulfonamide was obtained.
【００４９】ｍ．ｐ．２０５〜２０６℃M. p. 205-206 ° C
【００５０】実施例２〜２５ 実施例１（１）〜（５）の方法で得たＮ−（５−エチル
オキサリルアミノ−４−ニトロ−２−フェノキシフェニ
ル）メタンスルホンアミドを原料として実施例１（６）
で用いたｎ−ペンチルアミンの代わりに下記のアミン類
を用いた他は実施例１（６）と同様にすることにより、
表１−１、２に示した本発明の化合物を得た。ただし、
各化合物の再結晶溶媒については表１、２に示した溶媒
を用いた。Examples 2 to 25 Example 1 Using N- (5-ethyloxalylamino-4-nitro-2-phenoxyphenyl) methanesulfonamide obtained by the method of (1) to (5) as a raw material, Example 1 (6)
By the same procedure as in Example 1 (6) except that the following amines were used in place of the n-pentylamine used in 1.
The compounds of the present invention shown in Tables 1-1 and 2 were obtained. However,
As the recrystallization solvent for each compound, the solvents shown in Tables 1 and 2 were used.
【００５１】［アミン類］ｎ−プロピルアミン、ｎ−ブ
チルアミン、ｎ−ヘキシルアミン、ｎ−ヘプチルアミ
ン、イソプロピルアミン、イソブチルアミン、ｔ−ブチ
ルアミン、シクロプロピルアミン、シクロブチルアミ
ン、シクロペンチルアミン、シクロヘキシルアミン、シ
クロオクチルアミン、シクロプロピルメチルアミン、ア
リルアミン、２−ヒドロキシエチルアミン、２，３−ジ
ヒドロキシプロピルアミン、ベンジルアミン、ジエチル
アミン、ピロリジン、ピペリジン、ヘキサメチレンイミ
ン、ヘプタメチレンイミン、モルホリン、１−ジフェニ
ルメチルピペラジン[Amines] n-propylamine, n-butylamine, n-hexylamine, n-heptylamine, isopropylamine, isobutylamine, t-butylamine, cyclopropylamine, cyclobutylamine, cyclopentylamine, cyclohexylamine, cyclo Octylamine, cyclopropylmethylamine, allylamine, 2-hydroxyethylamine, 2,3-dihydroxypropylamine, benzylamine, diethylamine, pyrrolidine, piperidine, hexamethyleneimine, heptamethyleneimine, morpholine, 1-diphenylmethylpiperazine.
【００５２】[0052]
【表１】 [Table 1]
【００５３】注）ＴＨＦ：テトラヒドロフラン、ｎ−Ｈ
ｅｘａｎｅ；ｎ−ヘキサン、ＥｔＯＨ：エタノール、Ａ
ｃｅｔｏｎｅ：アセトンNote) THF: tetrahydrofuran, n-H
exane; n-hexane, EtOH: ethanol, A
cetone: acetone
【００５４】[0054]
【表２】 [Table 2]
【００５５】注）ＴＨＦ：テトラヒドロフラン、ｎ−Ｈ
ｅｘａｎｅ；ｎ−ヘキサン、ＥｔＯＨ：エタノール、Ａ
ｃｅｔｏｎｅ：アセトン 実施例２６〜３０ （１）６０％水素化ナトリウム７２．０ｇを含むクロロ
ベンゼン２５００ｍｌ溶液に室温でシクロヘキサノール
１７４．０ｇ、トリス［２−（２−メトキシエトキシ）
エチル］アミン１０．０ｍｌを順に加え、３０分間攪拌
後、氷冷下、実施例１の方法で得たＮ−（２−フルオロ
−５−ニトロフェニル）メタンスルホンアミド１３６．
０ｇを加え、室温で１６時間攪拌した。反応液に３規定
塩酸１５００ｍｌを加え、ジクロロメタンで抽出後、有
機層を水、飽和食塩水の順で洗浄し、無水硫酸マグネシ
ウムで乾燥した。溶媒を留去後、残渣をエタノールで再
結晶して、淡黄色針状晶のＮ−（２−シクロヘキシルオ
キシ−５−ニトロフェニル）メタンスルホンアミド１３
１．０ｇを得た。Note) THF: tetrahydrofuran, n-H
exane; n-hexane, EtOH: ethanol, A
Cetone: Acetone Examples 26 to 30 (1) To a 2500 ml solution of chlorobenzene containing 72.0 g of 60% sodium hydride, 174.0 g of cyclohexanol and tris [2- (2-methoxyethoxy)] at room temperature.
Ethyl] amine (10.0 ml) was added in that order, and the mixture was stirred for 30 minutes and then cooled with ice to obtain N- (2-fluoro-5-nitrophenyl) methanesulfonamide 136.
0 g was added, and the mixture was stirred at room temperature for 16 hours. 1500 ml of 3N hydrochloric acid was added to the reaction solution, the mixture was extracted with dichloromethane, the organic layer was washed with water and saturated brine in that order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was recrystallized from ethanol to give pale yellow needle crystals of N- (2-cyclohexyloxy-5-nitrophenyl) methanesulfonamide 13
1.0 g was obtained.
【００５６】ｍ．ｐ．１０５〜１０６．５℃M. p. 105-106.5 ° C
【００５７】（２）Ｎ−（２−シクロヘキシルオキシ−
５−ニトロフェニル）メタンスルホンアミドを実施例１
（３）の方法と同様に還元することにより、Ｎ−（５−
アミノ−２−シクロヘキシルオキシフェニル）メタンス
ルホンアミドを得た。(2) N- (2-cyclohexyloxy-
5-nitrophenyl) methanesulfonamide was used in Example 1.
By reducing in the same manner as in the method (3), N- (5-
Amino-2-cyclohexyloxyphenyl) methanesulfonamide was obtained.
【００５８】ｍ．ｐ．１５１．５〜１５３．５℃M. p. 151.5-153.5 ° C
【００５９】（３）オキサリルクロリド８．０ｇを含む
ジクロロメタン２００ｍｌに氷冷下、ｎ−プロパノール
３．８ｇ、次いでピリジン５．０ｇを加え、１５分間撹
拌した。反応液を−７８℃で冷却下、Ｎ−（５−アミノ
−２−シクロヘキシルオキシフェニル）メタンスルホン
アミド１５．０ｇおよびピリジン５．０ｇを含むジクロ
ロメタン１００ｍｌ溶液を加え、室温で２０分間撹拌し
た。反応液に水を加え、ジクロロメタンで抽出後、有機
層を水、３規定塩酸、飽和食塩水の順で洗浄し、無水硫
酸マグネシウムで乾燥した。溶媒を留去後、残渣をエタ
ノールで再結晶して、無色結晶のＮ−［２−シクロヘキ
シルオキシ−５−（ｎ−プロピルオキサリルアミノ）フ
ェニル］メタンスルホンアミド１４．１ｇを得た。(3) To 200 ml of dichloromethane containing 8.0 g of oxalyl chloride, 3.8 g of n-propanol and then 5.0 g of pyridine were added under ice cooling, and the mixture was stirred for 15 minutes. The reaction solution was cooled at −78 ° C., 100 ml of a dichloromethane solution containing 15.0 g of N- (5-amino-2-cyclohexyloxyphenyl) methanesulfonamide and 5.0 g of pyridine was added, and the mixture was stirred at room temperature for 20 minutes. Water was added to the reaction solution and the mixture was extracted with dichloromethane. The organic layer was washed with water, 3N hydrochloric acid and saturated brine in that order, and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was recrystallized from ethanol to obtain 14.1 g of colorless crystals of N- [2-cyclohexyloxy-5- (n-propyloxalylamino) phenyl] methanesulfonamide.
【００６０】ｍ．ｐ．１５２〜１５３℃M. p. 152-153 ° C
【００６１】（４）Ｎ−［２−シクロヘキシルオキシ−
５−（ｎ−プロピルオキサリルアミノ）フェニル］メタ
ンスルホンアミドを実施例１（５）と同様にしてニトロ
化することにより、Ｎ−［２−シクロヘキシルオキシ−
４−ニトロ−５−（ｎ−プロピルオキサリルアミノ）フ
ェニル］メタンスルホンアミドを得た。(4) N- [2-cyclohexyloxy-
By nitrating 5- (n-propyloxalylamino) phenyl] methanesulfonamide in the same manner as in Example 1 (5), N- [2-cyclohexyloxy-
4-Nitro-5- (n-propyloxalylamino) phenyl] methanesulfonamide was obtained.
【００６２】ｍ．ｐ．１７６〜１７７℃M. p. 176-177 ° C
【００６３】（５）Ｎ−［２−シクロヘキシルオキシ−
４−ニトロ−５−（ｎ−プロピルオキサリルアミノ）フ
ェニル］メタンスルホンアミドと下記のアミン類を用
い、実施例１（６）と同様にすることにより、表２に示
した本発明の化合物を得た。ただし、各化合物の再結晶
溶媒については表２に示した溶媒を用いた。(5) N- [2-cyclohexyloxy-
4-nitro-5- (n-propyloxalylamino) phenyl] methanesulfonamide and the following amines were used and treated in the same manner as in Example 1 (6) to give the compounds of the present invention shown in Table 2. It was However, as the recrystallization solvent for each compound, the solvents shown in Table 2 were used.
【００６４】［アミン類］ｎ−ペンチルアミン、ｎ−ヘ
キシルアミン、アリルアミン、ピペリジン、ヘキサメチ
レンイミン[Amines] n-pentylamine, n-hexylamine, allylamine, piperidine, hexamethyleneimine
【００６５】[0065]
【表３】 [Table 3]
【００６６】注）ＴＨＦ：テトラヒドロフラン、ｎ−Ｈ
ｅｘａｎｅ；ｎ−ヘキサン、ＥｔＯＨ：エタノール、Ａ
ｃｅｔｏｎｅ：アセトンNote) THF: tetrahydrofuran, n-H
exane; n-hexane, EtOH: ethanol, A
cetone: acetone
フロントページの続き (51)Int.Cl.5 識別記号 庁内整理番号 ＦＩ 技術表示箇所 Ａ６１Ｋ 31/18 ＡＢＥ 9283−4Ｃ ＡＢＦ 9283−4Ｃ (72)発明者 柏 真理子 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内 (72)発明者 畑山 勝男 東京都豊島区高田３丁目24番１号 大正製 薬株式会社内Continuation of the front page (51) Int.Cl. 5 Identification number Reference number within the agency FI Technical indication location A61K 31/18 ABE 9283-4C ABF 9283-4C (72) Inventor Mariko Kashiwa 3-24 Takada, Toshima-ku, Tokyo No. 1 within Taisho Pharmaceutical Co., Ltd. (72) Inventor Katsuo Hatayama 3-24-1 Takada, Toshima-ku, Tokyo Within Taisho Pharmaceutical Co., Ltd.
Claims (1)
り、Ｒ2はフェニル基または炭素原子数５〜７個のシク
ロアルキル基であり、Ｒ3は水素原子または炭素原子数
１〜４個のアルキル基であり、Ｒ4は炭素原子数１〜８
個のアルキル基、炭素原子数３〜８個のシクロアルキル
基、炭素原子数４〜６個のシクロアルキルメチル基、炭
素原子数３〜５個のアルケニル基、炭素原子数２〜４個
のヒドロキシアルキル基またはベンジル基であるか、Ｒ
3とＲ4が一緒になって５〜９員環の複素環を示す。）で
表わされるオキサミドを有するスルホンアニリド化合
物。1. A formula (In the formula, R 1 is an alkyl group having 1 to 3 carbon atoms, R 2 is a phenyl group or a cycloalkyl group having 5 to 7 carbon atoms, and R 3 is a hydrogen atom or 1 carbon atom. To 4 alkyl groups, R 4 has 1 to 8 carbon atoms
Alkyl groups, cycloalkyl groups having 3 to 8 carbon atoms, cycloalkylmethyl groups having 4 to 6 carbon atoms, alkenyl groups having 3 to 5 carbon atoms, hydroxy having 2 to 4 carbon atoms Alkyl group or benzyl group, R
3 and R 4 together represent a 5- to 9-membered heterocycle. ) A sulfonanilide compound having an oxamide represented by:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4251725A JPH06100525A (en) | 1992-09-21 | 1992-09-21 | Oxamide-containing sulfonanilide compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4251725A JPH06100525A (en) | 1992-09-21 | 1992-09-21 | Oxamide-containing sulfonanilide compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06100525A true JPH06100525A (en) | 1994-04-12 |
Family
ID=17227048
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4251725A Pending JPH06100525A (en) | 1992-09-21 | 1992-09-21 | Oxamide-containing sulfonanilide compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06100525A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994019318A1 (en) * | 1993-02-19 | 1994-09-01 | Taisho Pharmaceutical Co., Ltd. | 5-aminoacetylaminosulfonanilide compound |
-
1992
- 1992-09-21 JP JP4251725A patent/JPH06100525A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994019318A1 (en) * | 1993-02-19 | 1994-09-01 | Taisho Pharmaceutical Co., Ltd. | 5-aminoacetylaminosulfonanilide compound |
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