DE2418217A1 - Sulphamide acid esters as diuretics - prepd. from phenols and amidosulphonic acid chloride - Google Patents
Sulphamide acid esters as diuretics - prepd. from phenols and amidosulphonic acid chlorideInfo
- Publication number
- DE2418217A1 DE2418217A1 DE2418217A DE2418217A DE2418217A1 DE 2418217 A1 DE2418217 A1 DE 2418217A1 DE 2418217 A DE2418217 A DE 2418217A DE 2418217 A DE2418217 A DE 2418217A DE 2418217 A1 DE2418217 A1 DE 2418217A1
- Authority
- DE
- Germany
- Prior art keywords
- sulfamic acid
- alkyl
- ester
- general formula
- acid esters
- 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
- 150000002148 esters Chemical class 0.000 title abstract description 5
- 239000002253 acid Substances 0.000 title abstract 3
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 title abstract 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 title abstract 2
- 150000002989 phenols Chemical class 0.000 title description 5
- 239000002934 diuretic Substances 0.000 title description 2
- 229940030606 diuretics Drugs 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims abstract description 5
- 125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- -1 di-substituted phenyl Chemical group 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical class NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 claims description 8
- QAHVHSLSRLSVGS-UHFFFAOYSA-N sulfamoyl chloride Chemical compound NS(Cl)(=O)=O QAHVHSLSRLSVGS-UHFFFAOYSA-N 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 4
- 208000004880 Polyuria Diseases 0.000 claims description 3
- 239000002220 antihypertensive agent Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 3
- 230000001882 diuretic effect Effects 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 102000003846 Carbonic anhydrases Human genes 0.000 abstract description 2
- 108090000209 Carbonic anhydrases Proteins 0.000 abstract description 2
- 208000010412 Glaucoma Diseases 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 abstract 2
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 238000007086 side reaction Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SYOGDSKECGFKEP-UHFFFAOYSA-N (2,6-dichlorophenyl)sulfamic acid Chemical compound OS(=O)(=O)NC1=C(Cl)C=CC=C1Cl SYOGDSKECGFKEP-UHFFFAOYSA-N 0.000 description 2
- BLIQUPPBAQYIAX-UHFFFAOYSA-N (2,6-dimethylphenyl)sulfamic acid Chemical compound CC1=CC=CC(C)=C1NS(O)(=O)=O BLIQUPPBAQYIAX-UHFFFAOYSA-N 0.000 description 2
- WOBZEFNSIXMTAG-UHFFFAOYSA-N (3,4-dichlorophenyl)sulfamic acid Chemical compound ClC=1C=C(NS(=O)(=O)O)C=CC1Cl WOBZEFNSIXMTAG-UHFFFAOYSA-N 0.000 description 2
- KOSZSTGPTKFCLU-UHFFFAOYSA-N (3,5-dichlorophenyl)sulfamic acid Chemical compound OS(=O)(=O)NC1=CC(Cl)=CC(Cl)=C1 KOSZSTGPTKFCLU-UHFFFAOYSA-N 0.000 description 2
- OCQZTGVLKTWDON-UHFFFAOYSA-N (4-methoxyphenyl)sulfamic acid Chemical compound COC1=CC=C(NS(O)(=O)=O)C=C1 OCQZTGVLKTWDON-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
- PETRWTHZSKVLRE-UHFFFAOYSA-N 2-Methoxy-4-methylphenol Chemical compound COC1=CC(C)=CC=C1O PETRWTHZSKVLRE-UHFFFAOYSA-N 0.000 description 2
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 2
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Chemical compound OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- BEHLMOQXOSLGHN-UHFFFAOYSA-N benzenamine sulfate Chemical compound OS(=O)(=O)NC1=CC=CC=C1 BEHLMOQXOSLGHN-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- BFKZWJPWBGAKLZ-UHFFFAOYSA-N phenyl n-(oxomethylidene)sulfamate Chemical class O=C=NS(=O)(=O)OC1=CC=CC=C1 BFKZWJPWBGAKLZ-UHFFFAOYSA-N 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- RHODQQCOZUELPV-UHFFFAOYSA-N (2,3-dichlorophenyl)sulfamic acid Chemical compound OS(=O)(=O)NC1=C(Cl)C(Cl)=CC=C1 RHODQQCOZUELPV-UHFFFAOYSA-N 0.000 description 1
- JWMBNCBSVHSGAW-UHFFFAOYSA-N (2,3-dimethylphenyl)sulfamic acid Chemical compound CC1=CC=CC(NS(O)(=O)=O)=C1C JWMBNCBSVHSGAW-UHFFFAOYSA-N 0.000 description 1
- MPCVXQVIIJHCIP-UHFFFAOYSA-N (2,4-dichlorophenyl)sulfamic acid Chemical compound ClC1=CC=C(NS(=O)(=O)O)C(=C1)Cl MPCVXQVIIJHCIP-UHFFFAOYSA-N 0.000 description 1
- CUAWSPVPBAIBKR-UHFFFAOYSA-N (2,4-dimethylphenyl)sulfamic acid Chemical compound CC1=CC=C(NS(O)(=O)=O)C(C)=C1 CUAWSPVPBAIBKR-UHFFFAOYSA-N 0.000 description 1
- PHQHTEMSLKHUCH-UHFFFAOYSA-N (2,5-dichlorophenyl)sulfamic acid Chemical compound OS(=O)(=O)NC1=CC(Cl)=CC=C1Cl PHQHTEMSLKHUCH-UHFFFAOYSA-N 0.000 description 1
- RVZDSPAUIVBITB-UHFFFAOYSA-N (2,6-dimethoxyphenyl) sulfamate Chemical compound COC1=CC=CC(OC)=C1OS(N)(=O)=O RVZDSPAUIVBITB-UHFFFAOYSA-N 0.000 description 1
- DZHFDXPPDSLFSI-UHFFFAOYSA-N (2-chlorophenyl)sulfamic acid Chemical compound OS(=O)(=O)NC1=CC=CC=C1Cl DZHFDXPPDSLFSI-UHFFFAOYSA-N 0.000 description 1
- SJQLKTNUZIPAPJ-UHFFFAOYSA-N (2-methoxyphenyl) sulfamate Chemical compound COC1=CC=CC=C1OS(N)(=O)=O SJQLKTNUZIPAPJ-UHFFFAOYSA-N 0.000 description 1
- GEMYPJWUMFLPSQ-UHFFFAOYSA-N (2-methylphenyl)sulfamic acid Chemical compound CC1=CC=CC=C1NS(O)(=O)=O GEMYPJWUMFLPSQ-UHFFFAOYSA-N 0.000 description 1
- VWQOFYICQQNNBN-UHFFFAOYSA-N (3,4-dimethylphenyl)sulfamic acid Chemical compound CC1=C(C=CC(=C1)NS(=O)(=O)O)C VWQOFYICQQNNBN-UHFFFAOYSA-N 0.000 description 1
- PHMNWQAAZNEZKL-UHFFFAOYSA-N (3,5-dimethylphenyl)sulfamic acid Chemical compound CC1=CC(C)=CC(NS(O)(=O)=O)=C1 PHMNWQAAZNEZKL-UHFFFAOYSA-N 0.000 description 1
- BSLBIQWYMQGLBL-UHFFFAOYSA-N (3-chlorophenyl)sulfamic acid Chemical compound OS(=O)(=O)NC1=CC=CC(Cl)=C1 BSLBIQWYMQGLBL-UHFFFAOYSA-N 0.000 description 1
- IFKKKVMVPOPSFE-UHFFFAOYSA-N (3-methoxy-4-methylphenyl)sulfamic acid Chemical compound COC1=CC(NS(O)(=O)=O)=CC=C1C IFKKKVMVPOPSFE-UHFFFAOYSA-N 0.000 description 1
- LGUJIXYMVHQQGV-UHFFFAOYSA-N (3-methoxyphenyl) sulfamate Chemical compound COC1=CC=CC(OS(N)(=O)=O)=C1 LGUJIXYMVHQQGV-UHFFFAOYSA-N 0.000 description 1
- NYWIRXXZOLUIKT-UHFFFAOYSA-N (3-methoxyphenyl)sulfamic acid Chemical compound COC1=CC=CC(NS(O)(=O)=O)=C1 NYWIRXXZOLUIKT-UHFFFAOYSA-N 0.000 description 1
- UPHCJQPBZLPEHG-UHFFFAOYSA-N (3-methylphenyl)sulfamic acid Chemical compound CC1=CC=CC(NS(O)(=O)=O)=C1 UPHCJQPBZLPEHG-UHFFFAOYSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- PPZXCLZEVRYROB-UHFFFAOYSA-N (4-chlorophenyl)sulfamic acid Chemical compound OS(=O)(=O)NC1=CC=C(Cl)C=C1 PPZXCLZEVRYROB-UHFFFAOYSA-N 0.000 description 1
- HECPFUOGXBNARU-UHFFFAOYSA-N (4-ethoxyphenyl)sulfamic acid Chemical compound CCOC1=CC=C(NS(O)(=O)=O)C=C1 HECPFUOGXBNARU-UHFFFAOYSA-N 0.000 description 1
- XAQTXSHCLKDVCM-UHFFFAOYSA-N (4-methoxyphenyl) sulfamate Chemical compound COC1=CC=C(OS(N)(=O)=O)C=C1 XAQTXSHCLKDVCM-UHFFFAOYSA-N 0.000 description 1
- PGLRGMMNMUPZTG-UHFFFAOYSA-N (4-methylphenyl)sulfamic acid Chemical compound CC1=CC=C(NS(O)(=O)=O)C=C1 PGLRGMMNMUPZTG-UHFFFAOYSA-N 0.000 description 1
- TVKRUWKKKBQDFA-UHFFFAOYSA-N (4-phenylmethoxyphenyl)sulfamic acid Chemical compound C1=CC(NS(=O)(=O)O)=CC=C1OCC1=CC=CC=C1 TVKRUWKKKBQDFA-UHFFFAOYSA-N 0.000 description 1
- XRSKRSVTUVLURN-UHFFFAOYSA-N 1,3-benzodioxol-4-ol Chemical class OC1=CC=CC2=C1OCO2 XRSKRSVTUVLURN-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- SRNHSABWLTYDAF-UHFFFAOYSA-N 2,3-bis(phenylmethoxy)phenol Chemical class C=1C=CC=CC=1COC=1C(O)=CC=CC=1OCC1=CC=CC=C1 SRNHSABWLTYDAF-UHFFFAOYSA-N 0.000 description 1
- UMPSXRYVXUPCOS-UHFFFAOYSA-N 2,3-dichlorophenol Chemical class OC1=CC=CC(Cl)=C1Cl UMPSXRYVXUPCOS-UHFFFAOYSA-N 0.000 description 1
- IGXSSRPZRAIXQF-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-5-ol Chemical class O1CCOC2=C1C=CC=C2O IGXSSRPZRAIXQF-UHFFFAOYSA-N 0.000 description 1
- QSZCGGBDNYTQHH-UHFFFAOYSA-N 2,3-dimethoxyphenol Chemical class COC1=CC=CC(O)=C1OC QSZCGGBDNYTQHH-UHFFFAOYSA-N 0.000 description 1
- UXZNREKNBHZYIT-UHFFFAOYSA-N 2-chloro-3,5-dimethoxyphenol Chemical compound COC1=CC(O)=C(Cl)C(OC)=C1 UXZNREKNBHZYIT-UHFFFAOYSA-N 0.000 description 1
- QGLVWTFUWVTDEQ-UHFFFAOYSA-N 2-chloro-3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1Cl QGLVWTFUWVTDEQ-UHFFFAOYSA-N 0.000 description 1
- GNVRRKLFFYSLGT-UHFFFAOYSA-N 2-chloro-4-methoxyphenol Chemical compound COC1=CC=C(O)C(Cl)=C1 GNVRRKLFFYSLGT-UHFFFAOYSA-N 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- SHESIBIEPSTHMZ-UHFFFAOYSA-N 2-methoxy-3-methylphenol Chemical compound COC1=C(C)C=CC=C1O SHESIBIEPSTHMZ-UHFFFAOYSA-N 0.000 description 1
- CCZCXFHJMKINPE-UHFFFAOYSA-N 2-phenylmethoxyphenol Chemical compound OC1=CC=CC=C1OCC1=CC=CC=C1 CCZCXFHJMKINPE-UHFFFAOYSA-N 0.000 description 1
- LXUHYMCTFZFCCV-UHFFFAOYSA-N 3,5-dimethoxy-2-methylphenol Chemical compound COC1=CC(O)=C(C)C(OC)=C1 LXUHYMCTFZFCCV-UHFFFAOYSA-N 0.000 description 1
- UXGHDWLJFHAOMB-UHFFFAOYSA-N 3,5-dimethoxy-4-methylphenol Chemical compound COC1=CC(O)=CC(OC)=C1C UXGHDWLJFHAOMB-UHFFFAOYSA-N 0.000 description 1
- JMRPFKGSKYTUSD-UHFFFAOYSA-N 3-chloro-2-methoxyphenol Chemical compound COC1=C(O)C=CC=C1Cl JMRPFKGSKYTUSD-UHFFFAOYSA-N 0.000 description 1
- DXUDPAQOAABPAE-UHFFFAOYSA-N 3-chloro-4-methoxyphenol Chemical compound COC1=CC=C(O)C=C1Cl DXUDPAQOAABPAE-UHFFFAOYSA-N 0.000 description 1
- HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 description 1
- SIRZAUFJHUZRTI-UHFFFAOYSA-N 3-methoxy-2-methylphenol Chemical compound COC1=CC=CC(O)=C1C SIRZAUFJHUZRTI-UHFFFAOYSA-N 0.000 description 1
- SOYWOKSOKVRZRZ-UHFFFAOYSA-N 3-methoxy-4-methylphenol Chemical compound COC1=CC(O)=CC=C1C SOYWOKSOKVRZRZ-UHFFFAOYSA-N 0.000 description 1
- FOTVZLOJAIEAOY-UHFFFAOYSA-N 3-phenylmethoxyphenol Chemical compound OC1=CC=CC(OCC=2C=CC=CC=2)=C1 FOTVZLOJAIEAOY-UHFFFAOYSA-N 0.000 description 1
- MCNYXXKSYJPETB-UHFFFAOYSA-N 4-chloro-1,3-benzodioxol-5-ol Chemical compound OC1=CC=C2OCOC2=C1Cl MCNYXXKSYJPETB-UHFFFAOYSA-N 0.000 description 1
- FVZQMMMRFNURSH-UHFFFAOYSA-N 4-chloro-2-methoxyphenol Chemical compound COC1=CC(Cl)=CC=C1O FVZQMMMRFNURSH-UHFFFAOYSA-N 0.000 description 1
- FMHHCUBLAXNVHV-UHFFFAOYSA-N 4-chloro-3,5-dimethoxyphenol Chemical compound COC1=CC(O)=CC(OC)=C1Cl FMHHCUBLAXNVHV-UHFFFAOYSA-N 0.000 description 1
- NKFRBXPBRPYULV-UHFFFAOYSA-N 4-chloro-3-methoxyphenol Chemical compound COC1=CC(O)=CC=C1Cl NKFRBXPBRPYULV-UHFFFAOYSA-N 0.000 description 1
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 1
- PKDVWOVKDPEBQF-UHFFFAOYSA-N 4-methoxy-2-methylphenol Chemical compound COC1=CC=C(O)C(C)=C1 PKDVWOVKDPEBQF-UHFFFAOYSA-N 0.000 description 1
- ILASIIGKRFKNQC-UHFFFAOYSA-N 4-methoxy-3-methylphenol Chemical compound COC1=CC=C(O)C=C1C ILASIIGKRFKNQC-UHFFFAOYSA-N 0.000 description 1
- ZBFVXNCYGRJZCR-UHFFFAOYSA-N 4-methyl-1,3-benzodioxol-5-ol Chemical compound C1=C(O)C(C)=C2OCOC2=C1 ZBFVXNCYGRJZCR-UHFFFAOYSA-N 0.000 description 1
- VORLUZQKYXZUOU-UHFFFAOYSA-N 5-methyl-2,3-dihydro-1,4-benzodioxin-6-ol Chemical compound O1CCOC2=C1C=CC(O)=C2C VORLUZQKYXZUOU-UHFFFAOYSA-N 0.000 description 1
- HBXUEGAVTFDRBS-UHFFFAOYSA-N 5-methyl-2,3-dihydro-1,4-benzodioxin-7-ol Chemical compound O1CCOC2=C1C=C(O)C=C2C HBXUEGAVTFDRBS-UHFFFAOYSA-N 0.000 description 1
- MYCBHJOBNMQASS-UHFFFAOYSA-N 6-chloro-1,3-benzodioxol-5-ol Chemical compound C1=C(Cl)C(O)=CC2=C1OCO2 MYCBHJOBNMQASS-UHFFFAOYSA-N 0.000 description 1
- FTPYWMZYQRYIIJ-UHFFFAOYSA-N 6-chloro-2,3-dihydro-1,4-benzodioxin-7-ol Chemical compound O1CCOC2=C1C=C(O)C(Cl)=C2 FTPYWMZYQRYIIJ-UHFFFAOYSA-N 0.000 description 1
- GPHCCEYMMRQWOU-UHFFFAOYSA-N 6-methyl-1,3-benzodioxol-4-ol Chemical compound OC1=CC(C)=CC2=C1OCO2 GPHCCEYMMRQWOU-UHFFFAOYSA-N 0.000 description 1
- JRFWKGNYNPPPLF-UHFFFAOYSA-N 6-methyl-1,3-benzodioxol-5-ol Chemical compound C1=C(O)C(C)=CC2=C1OCO2 JRFWKGNYNPPPLF-UHFFFAOYSA-N 0.000 description 1
- GBZXQCMHMHDNBQ-UHFFFAOYSA-N 7-chloro-1,3-benzodioxol-4-ol Chemical compound OC1=CC=C(Cl)C2=C1OCO2 GBZXQCMHMHDNBQ-UHFFFAOYSA-N 0.000 description 1
- PAFVOQQFUJMVTI-UHFFFAOYSA-N 7-chloro-2,3-dihydro-1,4-benzodioxin-5-ol Chemical compound O1CCOC2=C1C=C(Cl)C=C2O PAFVOQQFUJMVTI-UHFFFAOYSA-N 0.000 description 1
- AZFJNJBWYLRCOA-UHFFFAOYSA-N 7-methyl-1,3-benzodioxol-5-ol Chemical compound CC1=CC(O)=CC2=C1OCO2 AZFJNJBWYLRCOA-UHFFFAOYSA-N 0.000 description 1
- GQZVRYGZITYLRD-UHFFFAOYSA-N 7-methyl-2,3-dihydro-1,4-benzodioxin-5-ol Chemical compound O1CCOC2=CC(C)=CC(O)=C21 GQZVRYGZITYLRD-UHFFFAOYSA-N 0.000 description 1
- KEDUGVYOOCPDOD-UHFFFAOYSA-N 7-methyl-2,3-dihydro-1,4-benzodioxin-6-ol Chemical compound O1CCOC2=C1C=C(C)C(O)=C2 KEDUGVYOOCPDOD-UHFFFAOYSA-N 0.000 description 1
- DKTYTKPBNMPYMD-UHFFFAOYSA-N 8-methyl-2,3-dihydro-1,4-benzodioxin-5-ol Chemical compound O1CCOC2=C1C(O)=CC=C2C DKTYTKPBNMPYMD-UHFFFAOYSA-N 0.000 description 1
- KIJOVVKQAUXOGQ-UHFFFAOYSA-N COC1=CC=CC(NS(O)(=O)=O)=C1OC Chemical compound COC1=CC=CC(NS(O)(=O)=O)=C1OC KIJOVVKQAUXOGQ-UHFFFAOYSA-N 0.000 description 1
- 101100387923 Caenorhabditis elegans dos-1 gene Proteins 0.000 description 1
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 1
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229950011260 betanaphthol Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- VQKLRVZQQYVIJW-UHFFFAOYSA-N dihydralazine Chemical compound C1=CC=C2C(NN)=NN=C(NN)C2=C1 VQKLRVZQQYVIJW-UHFFFAOYSA-N 0.000 description 1
- 229960002877 dihydralazine Drugs 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- INZGOWIHIBOARI-UHFFFAOYSA-N ethyl n-chlorosulfonylcarbamate Chemical class CCOC(=O)NS(Cl)(=O)=O INZGOWIHIBOARI-UHFFFAOYSA-N 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- WQVAYGCXSJMPRT-UHFFFAOYSA-N guanacline Chemical compound CC1=CCN(CCN=C(N)N)CC1 WQVAYGCXSJMPRT-UHFFFAOYSA-N 0.000 description 1
- 229950006795 guanacline Drugs 0.000 description 1
- ACGDKVXYNVEAGU-UHFFFAOYSA-N guanethidine Chemical compound NC(N)=NCCN1CCCCCCC1 ACGDKVXYNVEAGU-UHFFFAOYSA-N 0.000 description 1
- 229960003602 guanethidine Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- DVTUJXGMJVRSEZ-UHFFFAOYSA-N naphthalen-1-yl sulfamate Chemical compound C1=CC=C2C(OS(=O)(=O)N)=CC=CC2=C1 DVTUJXGMJVRSEZ-UHFFFAOYSA-N 0.000 description 1
- XFSXWFOXECTCPD-UHFFFAOYSA-N naphthalen-1-ylsulfamic acid Chemical compound C1=CC=C2C(NS(=O)(=O)O)=CC=CC2=C1 XFSXWFOXECTCPD-UHFFFAOYSA-N 0.000 description 1
- GQQGUUOAPRUTQW-UHFFFAOYSA-N naphthalen-2-yl sulfamate Chemical compound C1=CC=CC2=CC(OS(=O)(=O)N)=CC=C21 GQQGUUOAPRUTQW-UHFFFAOYSA-N 0.000 description 1
- CVQSVFTZCRZRBT-UHFFFAOYSA-N naphthalen-2-ylsulfamic acid Chemical compound C1=CC=CC2=CC(NS(=O)(=O)O)=CC=C21 CVQSVFTZCRZRBT-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 1
- 229960003147 reserpine Drugs 0.000 description 1
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003739 xylenols Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
- C07D317/64—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Sulfamidsäureester und Verfahren zu ihrer Herstellung Gegenstand der vorliegenden Erfindung sind Sulfamidsäureester der allgemeinen Formel I Ar - O - S02 - NH2 (I) in der Ar einen in 2-Stellung durch die Methylgruppe oder ein Halogenatom, in 2- oder 3-Stellung durch die Methoxygruppe, in 3- und 5-Stellung durch 2 Halogenatome, oder in beliebiger Stellung durch Alkyl-, oder Alkoxygruppen mit 2 - 4 C-Atomen mono- substituierten oder in beliebiger Stellung durch 2 Alkylgruppen mit 2 - 4 C-Atomen, 2 Alkoxygruppen, 2 Aralkoxygruppen mit 1 - 4 C-Atomen im Alkylteil oder eine Alkylendioxygruppe mit 1 - 4 C-Atomen di-substituierten Phenylrest oder einen 1- oder 2-Naphthylrest bedeutet.Sulfamic acid esters and process for their preparation are the subject of present invention are sulfamic acid esters of the general formula I Ar - O - S02 - NH2 (I) in the Ar one in the 2-position through the methyl group or a halogen atom, in the 2- or 3-position by the methoxy group, in the 3- and 5-position by 2 halogen atoms, or in any position by alkyl or alkoxy groups with 2-4 carbon atoms monosubstituted or in any position by 2 alkyl groups with 2-4 C atoms, 2 alkoxy groups, 2 aralkoxy groups with 1 - 4 C atoms in the alkyl part or an alkylenedioxy group with 1 - 4 carbon atoms di-substituted phenyl radical or a 1- or 2-naphthyl radical.
Gegenstand der Erfindung ist ferner ein Verfahren zur Herstellung von Sulfamidsäurearylestern der allgemeinen Formel II Ar' - 0 - SO2 - NH2 in der Ar' einen gegebenenfalls in beliebiger Stellung durch Alkyl-, Alkoxy- oder Alkylendioxygruppen mit 1 - 4 C-Atomen oder Halogenatome mono- oder di-substituierten Phenylrest oder den 1- oder 2-Naphthylrest bedeutet, das dadurch gekennzeichnet ist, daß man ein Phenol Ari-OH worin Ar' die obige Bedeutung besitzt,mit Amidosulfonsäurechlorid in einem organischen Lösungsmittel in Gegenwart einer Base umsetzt.The invention also relates to a method for production of aryl sulfamic acid esters of the general formula II Ar '- 0 - SO2 - NH2 in the Ar 'one optionally in any position by alkyl, alkoxy or alkylenedioxy groups with 1 - 4 carbon atoms or halogen atoms mono- or di-substituted phenyl radical or denotes the 1- or 2-naphthyl radical, which is characterized in that one Phenol Ari-OH in which Ar 'has the above meaning with amidosulfonic acid chloride in an organic solvent in the presence of a base.
Die Herstellung von Sulfamidsäurearylestern durch Umsetzung von Phenolen mit N-Chlorsulfonylisocyanat zu Chlorsulfonylurethanen, deren Umlagerung zu Phenoxysulfonylisocyanaten und anschließende Wasseranlagerung und Decarboxylierung ist bereits bekannt (DOS 1 593 846). Dieser Syntheseweg erfordert damit nicht nur 3 Stufen, sondern bei der Umlagerung zu den Phenoxysulfonylisocyanaten können auch Nebenreaktionen eintreten wie z.B. intramolekularar Ringschluß,wenn die verwendeten Phenole noch eine freie Orthoposition haben. Besonders ausgeprägt ist diese Nebenreaktion bei Alkylphenolen und Alkoxyphenolen (Lohaus, Chem. Ber. 105, 2791 (1972).The production of aryl sulfamic acid esters by converting phenols with N-chlorosulfonyl isocyanate to give chlorosulfonyl urethanes, their rearrangement to phenoxysulfonyl isocyanates and subsequent water attachment and decarboxylation is already known (DOS 1 593 846). This synthetic route thus not only requires 3 steps, but also the Rearrangement to the phenoxysulfonyl isocyanates can also cause side reactions such as intramolecular ring closure when the phenols used are still free Have orthoposition. This side reaction is particularly pronounced with alkylphenols and alkoxyphenols (Lohaus, Chem. Ber. 105, 2791 (1972).
Das erfindungsgemäße Verfahren benötigt für die Darstellung der Sulfamidsäurearylester nur einen Reaktionsschritt, indem das jeweilige Phenol bei etwa 400C in einem inerten organischen Lösungsmittel mit einem Überschuß an Amidosulfonsäurechlorid und einer Hilfsbase umgesetzt wird. Durch das Arbeiten bei niedrige-;ren Temperaturen wird die Nebenreaktion durch Substitution in Orthostellung vermieden.The process according to the invention is required for the preparation of the aryl sulfamic acid esters only one reaction step by adding the respective phenol at about 400C in an inert organic solvent with an excess of sulfamic acid chloride and one Auxiliary base is implemented. Working at lower temperatures will the side reaction avoided by substitution in the ortho position.
Das erfindungsgemäße Verfahren Verfahren verläuft daher überraschend einfach und ohne Nebenreaktionen und ist dem bisher bekannten Verfahren erheblich überlegen.The process according to the invention therefore proceeds surprisingly simple and without side reactions and is significant to the previously known process think.
Erfindungsgemäß kommen für das Herstellungsverfahren beispielsweise die folgenden Phenole Ar'-OH als Ausgangsstoffe in Betracht Phenol, 2-Methoxyphenol, 3-Methoxyphenol, 4-Methoxyphenol, alle isomeren Dimethoxyphenole, 2-Benzyloxyphenol, 3-Benzyloxyphenol, 4-Benzyloxyphenol, alle isomeren Bis-(benzyloxy)-phenole, alle isomeren Methylendioxyphenole, Äthylendioxyphenole, 2-Methylphenol, 3-Methylphenol, 4-Methylphenol, alle isomeren Dimethylphenole, 2-Chlorphenol, 3-Chlorphenol, 4-Chlorphenol, alle isomeren Dichlorphenole sowie 1-Naphthol und 2-Naphthol.According to the invention come for the manufacturing process, for example the following phenols Ar'-OH as starting materials into consideration phenol, 2-methoxyphenol, 3-methoxyphenol, 4-methoxyphenol, all isomeric dimethoxyphenols, 2-benzyloxyphenol, 3-Benzyloxyphenol, 4-Benzyloxyphenol, all isomeric bis (benzyloxy) phenols, all isomeric methylenedioxyphenols, ethylenedioxyphenols, 2-methylphenol, 3-methylphenol, 4-methylphenol, all isomeric dimethylphenols, 2-chlorophenol, 3-chlorophenol, 4-chlorophenol, all isomeric dichlorophenols as well as 1-naphthol and 2-naphthol.
Weiterhin kommen auch folgende verschiedenartig substituierte Phenole als Ausgangsstoffe in Betracht: 2-Methoxy-3-methylphenol, 2-Methoxy-4-methylphenol; 2-Methoxy-3-chlorphenol, 2-Methoxy-4-chlorphenol, 3-Methoxy-2-methylphenol, 3-Methoxy--4-methylphenol, 3-Methoxy-2-chlorphenol,3-Methoxy-4-chlorphenol, 4-Methoxy-2-methylphenol, 4-Methoxy-3-methylphenol, 4-Methoxy-2-chlorphenol, 4-Methoxy-3-chlorphenol, 3,5-Dimethoxy-2-methylphenol, 3,5-Dimethoxy-4-methylphenol, 3,5-Dimethoxy-2-chlorphenol, 3,5-Dimethoxy-4-chlorphenol, 2,3-Methylendioxy-4-methylphenol, 2,3-Methylendioxy-5-methylphenol, 2,3-Methylendioxy-6-methylphenol, 2,3-Methylendioxy-4-chlorphenol, 2,3-Methylendioxy-5-chlorphenol, 2,3-Methylendioxy-6-chlorphenol, 3, 4-Methylendioxy-2-methylphenol, 3,4-Methylendioxy-5-methylphenol, 3,4-Methylendioxy-6-methylphenol, 3,4-Methylendioxy-2-chlorphenol, 3,4-Methylendioxy-5-chlorphenol, 3,4-Methylendioxy-6-chlorphenol, 2,3-Äthylendioxy-4-methylphenol, 2,3-Äthylendioxy-5-methylphenol, 2,3-Äthylendioxy-6-methylphenol, 2, 3-Äthylendioxy-4-chlorphenol, 2, 3-Äthylendioxy-5-chlorphenol, 2, 3-Äthylendioxy-6-chlorphenol, 3, 4-Äthy lendioxy-2-methylphenol, 3, 4-Äthylendioxy-5-methylphenol, 3,4-Äthylendioxy-6-methylphenol, 3,4-Äthylendioxy-2-chlorphenol, 3,4-Äthylendioxy-5-chlorphenol, 3,4-Äthylendioxy-6-chlorphenol.The following variously substituted phenols also come Possible starting materials: 2-methoxy-3-methylphenol, 2-methoxy-4-methylphenol; 2-methoxy-3-chlorophenol, 2-methoxy-4-chlorophenol, 3-methoxy-2-methylphenol, 3-methoxy - 4-methylphenol, 3-methoxy-2-chlorophenol, 3-methoxy-4-chlorophenol, 4-methoxy-2-methylphenol, 4-methoxy-3-methylphenol, 4-methoxy-2-chlorophenol, 4-methoxy-3-chlorophenol, 3,5-dimethoxy-2-methylphenol, 3,5-dimethoxy-4-methylphenol, 3,5-dimethoxy-2-chlorophenol, 3,5-dimethoxy-4-chlorophenol, 2,3-methylenedioxy-4-methylphenol, 2,3-methylenedioxy-5-methylphenol, 2,3-methylenedioxy-6-methylphenol, 2,3-methylenedioxy-4-chlorophenol, 2,3-methylenedioxy-5-chlorophenol, 2,3-methylenedioxy-6-chlorophenol, 3, 4-methylenedioxy-2-methylphenol, 3,4-methylenedioxy-5-methylphenol, 3,4-methylenedioxy-6-methylphenol, 3,4-methylenedioxy-2-chlorophenol, 3,4-methylenedioxy-5-chlorophenol, 3,4-methylenedioxy-6-chlorophenol, 2,3-ethylenedioxy-4-methylphenol, 2,3-ethylenedioxy-5-methylphenol, 2,3-ethylenedioxy-6-methylphenol, 2,3-ethylenedioxy-4-chlorophenol, 2,3-ethylenedioxy-5-chlorophenol, 2,3-ethylenedioxy-6-chlorophenol, 3, 4-Ethylenedioxy-2-methylphenol, 3, 4-Ethylenedioxy-5-methylphenol, 3,4-ethylenedioxy-6-methylphenol, 3,4-ethylenedioxy-2-chlorophenol, 3,4-ethylenedioxy-5-chlorophenol, 3,4-ethylenedioxy-6-chlorophenol.
Die Umsetzung wird vorteilhaft so durchgeführt, daß man zu einer Lösung des Amidosulfonsäurechlorids eine zweite Lösung aus Phenol und Hilfsbase so zutropfen läßt, daß sich die Lösung durch die entstehende Reaktionswärme schwach erwärmt.The reaction is advantageously carried out in such a way that a solution is obtained of the sulfamic acid chloride, add a second solution of phenol and auxiliary base dropwise allows the solution to be slightly warmed by the heat of reaction produced.
Im allgemeinen wird die Reaktion in einem inerten organischen Lösungsmittel durchgeführt, vorzugsweise Methylenchlorid oder Benzol. Es können aber beispielsweise auch Tetrachlorkohlenstoff, Toluol' Dioxan, Tetrahydrofuran verwendet werden. Als Basen finden vorwiegend tertiäre organische Basen Verwendung, vorzugsweise zum Beispiel Triäthylamin, Pyridin, N-Methylpiperidin.Generally the reaction is carried out in an inert organic solvent carried out, preferably methylene chloride or benzene. But it can, for example carbon tetrachloride, toluene, dioxane, tetrahydrofuran can also be used. as Bases are predominantly used with tertiary organic bases, preferably for example Triethylamine, pyridine, N-methylpiperidine.
Das Reaktionsgemisch wird aufgearbeitet, indem man die erhaltene Lösung, gegebenenfalls nach Zusatz eines zweiten Lösungsmittels, mit 2n HCl extrahiert, trocknet und einengt. Dabei fällt das Rohprodukt aus. In ten meisten Fällen werden die Rohprodukte noch durch Umkristallisieren aus einem geeigneten Lösungsmittel, wie z.B. Toluol, gereinigt. Gegebenenfalls kann für die Reinigung auch eine Säulenchromatographie durchgeführt werden.The reaction mixture is worked up by the solution obtained, optionally after adding a second solvent, extracted with 2N HCl, dries and narrows. The crude product precipitates in the process. In most cases this will be the crude products by recrystallization from a suitable solvent, such as toluene, purified. If necessary, column chromatography can also be used for the purification be performed.
Als Verbindungen gemäß Anspruch 2 können außer den in den Beispielen angegebenen Verbindungen hergestellt werden: Sulfamidsäure-2-methoxyphenylester, Sulfamidsäure-3-methoxyphenylester, Sulfamidsäure-4-methoxyphenylester, Sulfamidsäure-2,3-dimethoxyphenylester, Sulfaminsäure-2,4-dimethoxyphenylester, Sulfamidsäure-2, 5-dimethoxyphenylester, Sulfamidsäure-2, 6-dimethoxyphenylester, Sulfamidsäure-3,4-dimethoxyphenylester, Sulfamidsäure-3,5-dimethoxyphenylester, sowie entsprechende Verbindungen in denen der Wortteil "dimethoxy-" durch "diäthoxy-" ersetzt ist, Sulfamidsäure-2-benzyloxyphenylester, Sulfamidsäure-3-benzyloxyphenylester, Sulfamidsäure-4-benzyloxyphenylester, Sulfamidsäure-2, 3-bis (benzyloxy)phenylester, Sulfamidsäure-2, 4-bis (benzyloxy)phenylester, Sulfamidsäure-2,5-bis(-benzyloxy)phenylester, Sulfamidsäure-2, 6-bis(benzyloxy)phenylester, Sulfamidsäure-3,4-bis(benzyloxy)phenyles Sulfamidsäure-3,5-bis (benzyloxy)phenylester, Sulfamidsäure-2, 3-methylendioxyphenylester, Sulfamidsäure-3, 4-methylendioxyphenylester, Sulfamidsäure-2, 3-äthylendioxyphenylester, Sulfamidsäurç-3,4-äthylendioxyphenylester, Sulfamidsäure-2-methylphenylester, Sulfamidsäure-3-methylphenylester, Sulfamidsäure-4-methylphenylester, Sulfamidsäure-2,3-dimethylphenylester, Sulfamidsäure-2,4-dimethylphenylester, Sulfamidsäure-2,5-dimethylphenylester, Sulfamidsäure-2,6-dimethylphenylester, Sulfamidsäure-3,4-dimethylphenylester, Sulfamidsäure-3,5-dimethylphenylester, Sulfamidsäure-2-chlorphenylester, Sulfamidsäure-3-chlorphenylester, Sulfamidsäure-4-chlorphenylester, Sulfamidsäure-2,3-dichlorphenylester, Sulfamidsäure-2,4-dichlorphenylester, Sulfamidsäure-2,5-dichlorphenylester, Sulfamidsäure-2,6-dichlorphenylester, Sulfamidsäure-3,4-dichlorphenylester, Sulfamidsäure-3,5-dichlorphenylester, Sulfamidsäure- 1 -naphthylester, Sulfamidsäure-2-naphthylester, Sulfamidsäure-2-methoxy-3-methylphneylester, Sulfamidsäure-2-methoxy-4-methylphenylester, Sulfamidsäure-2-methoxy-3-chlorphenylester, Sulfamidsäure-2-methoxy4-chlorphenylester, Sulfamidsäure-3-methoxy-2-methylphenylester, Sulfamidsäure-3-methoxy-4-methylphenylester, Sulfamidsäure-3-methoxy-2-chlorphenylester, Sulfamidsäure-3-methoxy-4-chlorphenylester Sulfamidsäure-4-methoxy-2-methylphenylester, Sulfamidsäure-4-methoxy-3-methylphenylester, Sulfamidsäure-4-methoxy-2-chlorphenyles ter, - Sulfamidsäure-4-methoxy-3-chlorphenylester, Sulfamidsäure-3,5-dimethoxy-2-methylphenylester, Sulfamidsäure-3, 5-dimethoxy-4-methylphenylester, Sulfamidsäure-3,5-dimethoxy-2-chlorphenylester, Sulfamidsäure-3,5-dimethoxy-4-chlorphenylester, sowie entsprechende Verbindungen in denen der Wortteil "dimethoxy-" durch "diäthoxy-" ersetzt ist, Sulfamidsäure-2,3-methylendioxy-4-methylphenylester, Sulfamidsäure-2, 3-methylendioxy-5-methylphenylester, Sulfamidsäure-2,3-methylendioxy-6-methylphenylester, Sulfamidsäure-2,3-methylendioxy-4-chlorphenylester, Sulfamidsäure-2,3-methylendioxy-5-chlorphenylester, Sulfamidsäure-2, 3-methylendioxy-6-chlorphenylester, Sulfamidsäure-3,4-methylendioxy-2-methylphenylester, Sulfamidsäure-3,4-methylendioxy-5-methylphenylester, Sulfamidsäure-3,4-methylendioxy-6-methylphenylester, Sulfamidsäure-3,4-methylendioxy-2-chlorphenylester, Sulfamidsäure-3, 4-methylendioxy-5-chlorphenylester, Sulfamidsäure-3,4-methylendioxy-6-chlorphenylester, Sulfamidsäure-2, 3-äthylendioxy-4-methylphenylester, Sulfamidsäure-2,3-äthylendioxy-5-methylphenylester, Sulfamidsäure-2,3-äthylendioxy-6-methylphenylester, Sulfamidsäure-2, 3-äthylendioxy-4-chlorphenylester, Sulfamidsäure-2, 3-äthylendioxy-5-chlorpllenylester, Sulfamidsäure-2,3-äthylendioxy-6-chlorphenylester, Sulfamidsäure-3, 4-äthylendioxy-2-methylphenylester, Sulfamidsäure-3, 4-äthylendioxy-5-methylphenylester, Sulfamidsäure-3, 4-äthylendioxy-6-methylphenylester, Sulfamidsäure-3,4-äthylendioxy-2-chlorphenylester, Sulfamidsäure-3,4-äthylendioxy-5-chlorphenylester, Sulfamidsäure-3, 4-äthylendioxy-6-chlorphenylester.As compounds according to claim 2, in addition to those in the examples specified compounds are prepared: sulfamic acid 2-methoxyphenyl ester, 3-methoxyphenyl sulfamic acid, 4-methoxyphenyl sulfamic acid, 2,3-dimethoxyphenyl sulfamic acid, 2,4-dimethoxyphenyl sulfamic acid, 2,5-dimethoxyphenyl sulfamic acid, Sulfamic acid-2, 6-dimethoxyphenyl ester, sulfamic acid 3,4-dimethoxyphenyl ester, sulfamic acid 3,5-dimethoxyphenyl ester, as well as corresponding compounds in which the word part "dimethoxy-" is replaced by "diethoxy-" is replaced, sulfamic acid 2-benzyloxyphenyl ester, sulfamic acid 3-benzyloxyphenyl ester, 4-benzyloxyphenyl sulfamic acid, 2,3-bis (benzyloxy) phenyl sulfamic acid, 2,4-bis (benzyloxy) phenyl sulfamic acid, 2,5-bis (benzyloxy) phenyl sulfamic acid, Sulfamic acid 2,6-bis (benzyloxy) phenyl ester, sulfamic acid 3,4-bis (benzyloxy) phenyl 3,5-bis (benzyloxy) phenyl sulfamic acid, 2,3-methylenedioxyphenyl sulfamic acid, 3, 4-methylenedioxyphenyl sulfamic acid, 2,3-ethylenedioxyphenyl sulfamic acid, 3,4-ethylenedioxyphenyl sulfamic acid, 2-methylphenyl sulfamic acid, 3-methylphenyl sulfamic acid, 4-methylphenyl sulfamic acid, 2,3-dimethylphenyl sulfamic acid, 2,4-dimethylphenyl sulfamic acid, 2,5-dimethylphenyl sulfamic acid, 2,6-dimethylphenyl sulfamic acid, 3,4-dimethylphenyl sulfamic acid, 3,5-dimethylphenyl sulfamic acid, 2-chlorophenyl sulfamic acid, 3-chlorophenyl sulfamic acid, 4-chlorophenyl sulfamic acid, 2,3-dichlorophenyl sulfamic acid, 2,4-dichlorophenyl sulfamic acid, 2,5-dichlorophenyl sulfamic acid, 2,6-dichlorophenyl sulfamic acid, 3,4-dichlorophenyl sulfamic acid, 3,5-dichlorophenyl sulfamic acid, 1-naphthyl sulfamic acid, 2-naphthyl sulfamic acid, Sulfamic acid 2-methoxy-3-methylphenyl ester, sulfamic acid 2-methoxy-4-methylphenyl ester, 2-methoxy-3-chlorophenyl sulfamic acid, 2-methoxy-4-chlorophenyl sulfamic acid, 3-methoxy-2-methylphenyl sulfamic acid, 3-methoxy-4-methylphenyl sulfamic acid, 3-methoxy-2-chlorophenyl sulfamic acid, 3-methoxy-4-chlorophenyl sulfamic acid 4-methoxy-2-methylphenyl sulfamic acid, 4-methoxy-3-methylphenyl sulfamic acid, 4-methoxy-2-chlorophenyl sulfamic acid, 4-methoxy-3-chlorophenyl sulfamic acid, Sulfamic acid 3,5-dimethoxy-2-methylphenyl ester, sulfamic acid 3,5-dimethoxy-4-methylphenyl ester, Sulfamic acid 3,5-dimethoxy-2-chlorophenyl ester, sulfamic acid 3,5-dimethoxy-4-chlorophenyl ester, as well as corresponding compounds in which the word part "dimethoxy-" is replaced by "diethoxy-" is replaced, sulfamic acid 2,3-methylenedioxy-4-methylphenyl ester, sulfamic acid-2, 3-methylenedioxy-5-methylphenyl ester, sulfamic acid 2,3-methylenedioxy-6-methylphenyl ester, 2,3-methylenedioxy-4-chlorophenyl sulfamic acid, 2,3-methylenedioxy-5-chlorophenyl sulfamic acid, Sulfamic acid 2, 3-methylenedioxy-6-chlorophenyl ester, sulfamic acid 3,4-methylenedioxy-2-methylphenyl ester, Sulfamic acid 3,4-methylenedioxy-5-methylphenyl ester, Sulfamic acid 3,4-methylenedioxy-6-methylphenyl ester, sulfamic acid 3,4-methylenedioxy-2-chlorophenyl ester, 3, 4-methylenedioxy-5-chlorophenyl sulfamic acid, 3,4-methylenedioxy-6-chlorophenyl sulfamic acid, 2,3-ethylenedioxy-4-methylphenyl sulfamic acid, 2,3-ethylenedioxy-5-methylphenyl sulfamic acid, 2,3-ethylenedioxy-6-methylphenyl sulfamic acid, 2,3-ethylenedioxy-4-chlorophenyl sulfamic acid, 2, 3-ethylenedioxy-5-chlorophenyl sulfamic acid, 2,3-ethylenedioxy-6-chlorophenyl sulfamic acid, 3, 4-ethylenedioxy-2-methylphenyl sulfamic acid, 3,4-ethylenedioxy-5-methylphenyl sulfamic acid, 3, 4-ethylenedioxy-6-methylphenyl sulfamic acid, 3,4-ethylenedioxy-2-chlorophenyl sulfamic acid, 3,4-ethylenedioxy-5-chlorophenyl sulfamic acid, 3,4-ethylenedioxy-6-chlorophenyl sulfamic acid.
Als erfindungsgemäße Verbindungen gemäß Anspruch 1 kommen außer den in den Beispielen angegebenen Verbindungen in Betracht: Sulfamidsäure-3-methoxyphenylester, Sulfamidsäure-4-äthoxyphenylester, Sulfamidsäure-3,5-diäthoxyphenylester, Sulfamidsäure-2,3-methylendioxyphenylester, Sulfamidsäure-2,3-äthylendioxyphenylester, Sulfamidsäure-3,4-äthylendioxyphenylester, Sulfamidsäure-2,6-dichlorphenylester, Sulfamidsäure-3,4-dichlorphenylester, Sulfamidsäure-3,5-dichlorphenylester.As compounds according to the invention according to claim 1 also come compounds given in the examples into consideration: sulfamic acid 3-methoxyphenyl ester, 4-ethoxyphenyl sulfamic acid, 3,5-diethoxyphenyl sulfamic acid, 2,3-methylenedioxyphenyl sulfamic acid, 2,3-ethylenedioxyphenyl sulfamic acid, 3,4-ethylenedioxyphenyl sulfamic acid, 2,6-dichlorophenyl sulfamic acid, 3,4-dichlorophenyl sulfamic acid, 3,5-dichlorophenyl sulfamic acid.
Die neuen Sulfamidsäureester sind gute Diuretika mit einer hervorragenden Wirkung als Carboanhydrasehemmer.The new sulfamic acid esters are good diuretics with an excellent one Effect as a carbonic anhydrase inhibitor.
Die erfindungsgemäßen Produkte stellen demnach wertvolle Therapeutika dar, die für die Erzeugung einer Diurese über eine Carbonanhydrasehemmung geeignet sind (Glaukombehandlung).The products according to the invention are therefore valuable therapeutics that are suitable for the generation of diuresis via a carbonic anhydrase inhibition are (glaucoma treatment).
Sie können als solche oder zusammen mit in der Galenik üblicherweise eingesetzten Hilfsstoffen in Form von Tabletten, Dragees, Kapseln, Lösungen oder Suspensionen appliziert werden.They can usually be used as such or together with in galenics used auxiliaries in the form of tablets, coated tablets, capsules, solutions or Suspensions are applied.
Die Wirkstoffmenge beträgt 50 mg bis 1000 mg, vorzugsweise 100 - 500 mg.The amount of active ingredient is 50 mg to 1000 mg, preferably 100-500 mg.
Für die parenterale Anwendung kommen vorzugsweise Lösungen oder Suspensionen in Wasser in Betracht. Es können aber auch andere physiologisch verträgliche Lösungsmittel, wie z.B.Solutions or suspensions are preferred for parenteral use in water. However, other physiologically compatible solvents can also be used, such as.
Äthanol, sowie Lösungsvermittler verwendet werden.Ethanol and solubilizers can be used.
Auch eine Kombination mit anderen Wirkstoffen ist möglich. Für die Kombination mit anderen Wirkstoffen, etwa mit Bludrucksenkern, eignen sich beispielsweise: Reserpin, Dihydralazin, Guanethidin, Guanaclin, Clonidin.A combination with other active ingredients is also possible. For the Combination with other active ingredients, for example with antihypertensive agents, are suitable, for example: Reserpine, dihydralazine, guanethidine, guanacline, clonidine.
Beispiele: Die neuen Sulfamidsäurearylester werden durch die Schmelzpunkte charakterisiert.Examples: The new aryl sulfamic acid esters are characterized by the melting points characterized.
Beispiel 1 Sulfamidsäurephenylester 70 g (0,6 Mol) Amidosulfonsäurechlorid werden in 500 ml trockenem Methylenchlorid gelöst. Zu dieser Lösung gibt man in 10 Minuten eine Lösung von 18,8 g (0,2 Mol) Phenol und 60,6 g (0,6 Mol) Triäthylamin in 300 ml trockenem Methylenchlorid. Dabei erwärmt sich-die Lösung auf etwa 40 Grad. Man läßt 2 Tage bei Raumtemperatur nachrühren und engt das Methylenchlorid im Vakuum ein. Der Rückstand wird mit 2n HOl versetzt und mehrfach ausgeäthert. Die vereinigten Ätherextrakte werden getrocknet und eingedampft. Man erhält 18,4 g Sulfamidsäurephenylester.Example 1 Phenyl sulfamic acid 70 g (0.6 mol) sulfamic acid chloride are dissolved in 500 ml of dry methylene chloride. For this solution one gives in 10 minutes a solution of 18.8 g (0.2 mol) of phenol and 60.6 g (0.6 mol) of triethylamine in 300 ml of dry methylene chloride. The solution heats up to about 40 degrees. The mixture is stirred for 2 days at room temperature and the methylene chloride is concentrated in vacuo a. The residue is mixed with 2N HOl and extracted with ether several times. The United Ether extracts are dried and evaporated. 18.4 g of phenyl sulfamic acid are obtained.
Fp 860 (aus Toluol).M.p. 860 (from toluene).
Beispiel 2 Sulfamidsäure-p-methoxyphenylester 23 g (0,2 Mol) Amidosulfonsäurechlorid werden in 200 ml absolutem Benzol gelöst. Zu dieser Lösung gibt man in 30 Minuten eine Lösung aus 6,2 g (0,05 Mol) p-Methoxyphenol, 20,2 g (0,2 Mol) Triäthylamin in 100 ml trockenem Benzol. Die Lösung erwärmt sich beim Zutropfen schwach, man rührt bei Raumtemperatur 3 Tage nach, zieht das Benzol im Vakuum ab, nimmt 2n HCl auf und extrahiert mehrmals mit Essigester. Die vereinigten Essigesterphasen werden getrocknet und eingeengt. Nach Zugabe von Cyclohexan erhält man 3,3 g Sulfamidsäure-p-methoxyphenylester vom Schmelzpunkt 650.Example 2 sulfamic acid p-methoxyphenyl ester 23 g (0.2 mol) sulfamic acid chloride are dissolved in 200 ml of absolute benzene. This solution is added in 30 minutes a solution of 6.2 g (0.05 mol) of p-methoxyphenol, 20.2 g (0.2 mol) of triethylamine in 100 ml of dry benzene. The solution heats up slightly when it is added dropwise, man stirs at room temperature for 3 days, removes the benzene in vacuo, takes 2N HCl and extracted several times with ethyl acetate. The combined ethyl acetate phases are dried and concentrated. After adding cyclohexane, 3.3 g of p-methoxyphenyl sulfamic acid are obtained from melting point 650.
Beispiel 3 Sulfamidsäure-ortho-methoxyphenylester Man arbeitet wie in Beispiel 1 und kristallisiert den Rückstand aus Isopropyläther / Cyclohexan um. Man erhält 9,8 g Sulfamidsäure-orthomethoxyphenyl-ester vom Schmelzpunkt 780.Example 3 Orthomethoxyphenyl sulfamic acid ester The procedure is as described in Example 1 and the residue crystallized from isopropyl ether / cyclohexane. 9.8 g of orthomethoxyphenyl sulfamic acid with a melting point of 780 are obtained.
Beispiel 4 Sulfamidsäure-para-benzyloxyphenyles ter Man arbeitet wie in Beispiel 1, jedoch mit vier Äquivalenten Amidosulfonsäurechlorid und Triäthylamin.Example 4 Sulphamic acid para-benzyloxyphenyl ester One works as in Example 1, but with four equivalents of sulfamic acid chloride and triethylamine.
Der Ätherrückstand wird zweimal aus Toluol umkristallisiert. Man erhält 19 g Sulfamidsäure-p-benzyloxyphenylester vom Schmelzpunkt 121°.The ether residue is recrystallized twice from toluene. You get 19 g of sulfamic acid p-benzyloxyphenyl ester of melting point 121 °.
Beispiel 5 Sulfamidsäure-p-chlorphenylester Man arbeitet wie in Beispiel 1 und erhält 22 g Sulfamidsäure-pchlorphenylester vom Schmelzpunkt 1040.Example 5 p-chlorophenyl sulfamic acid ester The procedure is as in example 1 and receives 22 g of sulfamic acid pchlorophenyl ester with a melting point of 1040.
Beispiel 6 Sulfamidsäure-3, 4-Methylendioxyphenylester 460 g (4 Mol) Amidosulfonsäurechlorid werden in 1 1 trockenem Methylenchlorid gelöst. Zu dieser Lösung tropft man während 2 Stunden eine Lösung von 70 g (0,5 Mol) 3,4-Methylendioxyphenol und 412 g (4,0 Mol) Triäthylamin in einem Liter trockenem Methylenchlorid. Die Lösung erwärmt sich auf 400 und wird 3 Tage nachgerührt. Man zieht das Lösungsmittel im Vakuum ab, versetzt den Rückstand mit 2n HCl und extrahiert mehrfach mit Methylenchlorid. Das Methylenchlorid wird getrocknet und zur Trockene eingedampft. Das. zurückbleibende Öl (63 g) wird über eine Kieselgelsäule (1,3 kg) mit Methylenchlorid als Laufmittel getrennt.Example 6 Sulphamic acid 3,4-methylenedioxyphenyl ester 460 g (4 mol) Amidosulfonic acid chloride are dissolved in 1 l of dry methylene chloride. To this A solution of 70 g (0.5 mol) of 3,4-methylenedioxyphenol is added dropwise to the solution over a period of 2 hours and 412 g (4.0 mol) of triethylamine in one liter of dry methylene chloride. The solution warms up to 400 and is stirred for 3 days. One pulls the solvent in Vacuum, treated the residue with 2N HCl and extracted several times with methylene chloride. The methylene chloride is dried and evaporated to dryness. That. lagging Oil (63 g) is passed through a silica gel column (1.3 kg) using methylene chloride as the mobile phase separated.
Man erhält 50 g Sulfamidsäure-3,4-methylendioxyphenylester vom Schmelzpunkt 72°.50 g of 3,4-methylenedioxyphenyl sulfamic acid with a melting point are obtained 72 °.
Beispiel 7 Sulfamidsäure-3, 5-dimethoxyphenylester Man arbeitet wie in Beispiel 1, jedoch mit 2 Äquivalenten Amidosulfonsäurechlorid und Triäthylamin. Der Ätherrückstand wird mit Methanol aufgenommen und durch Zugabe von Wasser wird der Sulfamidsäure-3,5-dimethoxyphenylester ausgefällt. Man erhält 12,5 g vom Schmelzpünkt 1110.Example 7 Sulphamic acid 3,5-dimethoxyphenyl ester The procedure is as follows in Example 1, but with 2 equivalents of sulfamic acid chloride and triethylamine. The ether residue is taken up with methanol and water is added the sulfamic acid 3,5-dimethoxyphenyl ester precipitated. 12.5 g of the melting point are obtained 1110.
Beispiel 8 Sulfamidsäure-2,6-dimethylphenylester Man arbeitet wie in Beispiel 4 und erhält nach dem Umkristalli-Toluol aus Toluol 16 g sieren aus Sulfamid6-dimethylphenylester vom Schmelzpunkt 109 . saure Beispiel 9 Sulfamidsåure-2-naphthylester Man arbeitet wie in Beispiel 4 und erhaält nach dem Umkristallisieren aus Toluol 12 g Sulfamidsäure-2-naphthylester vom Schmelzpunkt 1120.Example 8 2,6-Dimethylphenyl Sulphamic Acid The procedure is as follows in Example 4 and, after recrystallization of toluene from toluene, 16 g are obtained Sulphamid6-dimethylphenyl ester of melting point 109. acidic Example 9 2-naphthyl sulfamic acid ester The procedure is as in Example 4 and obtained after recrystallization from toluene 12 g of sulfamic acid 2-naphthyl ester, melting point 1120.
Beispiel 10 Sulfamidsäure-1-naphthylester Man arbeitet wie in Beispiel 4 und erhält nach dem Umkristallisieren aus Toluol 7g (16 %) Sulfamidsäure-1-naphthylester vom Schmelzpunkt 98°.Example 10 1-naphthyl sulfamic acid ester The procedure is as in example 4 and obtained after recrystallization from toluene 7 g (16%) sulfamic acid 1-naphthyl ester with a melting point of 98 °.
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2418217A DE2418217A1 (en) | 1974-04-13 | 1974-04-13 | Sulphamide acid esters as diuretics - prepd. from phenols and amidosulphonic acid chloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2418217A DE2418217A1 (en) | 1974-04-13 | 1974-04-13 | Sulphamide acid esters as diuretics - prepd. from phenols and amidosulphonic acid chloride |
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| Publication Number | Publication Date |
|---|---|
| DE2418217A1 true DE2418217A1 (en) | 1975-11-06 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2418217A Pending DE2418217A1 (en) | 1974-04-13 | 1974-04-13 | Sulphamide acid esters as diuretics - prepd. from phenols and amidosulphonic acid chloride |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1099706A3 (en) * | 1991-08-29 | 2002-09-04 | Sterix Limited | Estrane sulphamate derivatives as steroid sulphatase inhibitors |
| US6642397B1 (en) | 1991-08-28 | 2003-11-04 | Sterix Limited | Steroid sulphatase inhibitors |
| US6677325B2 (en) | 1991-08-28 | 2004-01-13 | Sterix Ltd. | Steroid sulphatase inhibitors |
| US6858597B2 (en) | 1999-12-13 | 2005-02-22 | Sterix Limited | Halogenated sulphamate-, phosphonate-, thiophosphonate-, sulphonate- and sulphonamide- compounds as inhibitors of steroid sulphatase |
| US7098199B2 (en) | 1991-08-29 | 2006-08-29 | Sterix Limited | Steroid sulphatase inhibitors |
| US7335650B2 (en) | 2000-01-14 | 2008-02-26 | Sterix Limited | Composition |
-
1974
- 1974-04-13 DE DE2418217A patent/DE2418217A1/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6642397B1 (en) | 1991-08-28 | 2003-11-04 | Sterix Limited | Steroid sulphatase inhibitors |
| US6677325B2 (en) | 1991-08-28 | 2004-01-13 | Sterix Ltd. | Steroid sulphatase inhibitors |
| EP1099706A3 (en) * | 1991-08-29 | 2002-09-04 | Sterix Limited | Estrane sulphamate derivatives as steroid sulphatase inhibitors |
| US7098199B2 (en) | 1991-08-29 | 2006-08-29 | Sterix Limited | Steroid sulphatase inhibitors |
| US6858597B2 (en) | 1999-12-13 | 2005-02-22 | Sterix Limited | Halogenated sulphamate-, phosphonate-, thiophosphonate-, sulphonate- and sulphonamide- compounds as inhibitors of steroid sulphatase |
| US7335650B2 (en) | 2000-01-14 | 2008-02-26 | Sterix Limited | Composition |
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