DE2734270C2 - - Google Patents
Info
- Publication number
- DE2734270C2 DE2734270C2 DE2734270A DE2734270A DE2734270C2 DE 2734270 C2 DE2734270 C2 DE 2734270C2 DE 2734270 A DE2734270 A DE 2734270A DE 2734270 A DE2734270 A DE 2734270A DE 2734270 C2 DE2734270 C2 DE 2734270C2
- Authority
- DE
- Germany
- Prior art keywords
- benzodioxan
- carboxamide
- filtered
- methyl
- pyrrolidylmethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- -1 1-benzyl-2-pyrrolidylmethyl group Chemical group 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 8
- 229940054066 benzamide antipsychotics Drugs 0.000 claims description 7
- 150000003936 benzamides Chemical class 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 2
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
- 239000000243 solution Substances 0.000 description 60
- 239000000203 mixture Substances 0.000 description 48
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 26
- 239000013078 crystal Substances 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 229960001701 chloroform Drugs 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- 239000002585 base Substances 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 18
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 238000011282 treatment Methods 0.000 description 14
- 229910021529 ammonia Inorganic materials 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 11
- UNRBEYYLYRXYCG-UHFFFAOYSA-N (1-ethylpyrrolidin-2-yl)methanamine Chemical compound CCN1CCCC1CN UNRBEYYLYRXYCG-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- RKSFKFSIQAQPHQ-UHFFFAOYSA-N 7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carbonyl chloride Chemical compound O1CCOC2=C1C=C(S(=O)(=O)NC)C=C2C(Cl)=O RKSFKFSIQAQPHQ-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 239000003610 charcoal Substances 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- JUFKJRCMBLLXNH-UHFFFAOYSA-N (1-methylpyrrolidin-2-yl)methanamine Chemical compound CN1CCCC1CN JUFKJRCMBLLXNH-UHFFFAOYSA-N 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- POVZSJGKGZYZPS-UHFFFAOYSA-N n-[(1-methylpyrrolidin-2-yl)methyl]-7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound C=1C(S(=O)(=O)NC)=CC=2OCCOC=2C=1C(=O)NCC1CCCN1C POVZSJGKGZYZPS-UHFFFAOYSA-N 0.000 description 7
- 239000008107 starch Substances 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 150000003857 carboxamides Chemical class 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 235000019359 magnesium stearate Nutrition 0.000 description 6
- 229920000609 methyl cellulose Polymers 0.000 description 6
- 239000001923 methylcellulose Substances 0.000 description 6
- NCSFGFOXYGSSSH-UHFFFAOYSA-N 7-chlorosulfonyl-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(Cl)(=O)=O)C=C2C(=O)O NCSFGFOXYGSSSH-UHFFFAOYSA-N 0.000 description 5
- AJEDNQSLTXJFJG-UHFFFAOYSA-N 7-ethylsulfonyl-2,3-dihydro-1,4-benzodioxine-5-carbonyl chloride Chemical compound O1CCOC2=C1C=C(S(=O)(=O)CC)C=C2C(Cl)=O AJEDNQSLTXJFJG-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- HTGKTSVPJJNEMQ-QMMMGPOBSA-N [(2s)-1-prop-2-enylpyrrolidin-2-yl]methanamine Chemical compound NC[C@@H]1CCCN1CC=C HTGKTSVPJJNEMQ-QMMMGPOBSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 230000002903 catalepsic effect Effects 0.000 description 5
- SXAKAOFKGIOPHK-UHFFFAOYSA-N methyl 7-sulfamoyl-2,3-dihydro-1,4-benzodioxine-5-carboxylate Chemical compound O1CCOC2=C1C=C(S(N)(=O)=O)C=C2C(=O)OC SXAKAOFKGIOPHK-UHFFFAOYSA-N 0.000 description 5
- KHDSNFILCIVZDT-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)NC)=CC2=C1OCCO2 KHDSNFILCIVZDT-UHFFFAOYSA-N 0.000 description 5
- YRXDDQLZROFCKK-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-7-ethylsulfonyl-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=CC2=C1OCCO2 YRXDDQLZROFCKK-UHFFFAOYSA-N 0.000 description 5
- XOPARDXSIMENIK-UHFFFAOYSA-N 7-(dimethylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carbonyl chloride Chemical compound O1CCOC2=C1C=C(S(=O)(=O)N(C)C)C=C2C(Cl)=O XOPARDXSIMENIK-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
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical class ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- ZRISRDUHJZSFSK-UHFFFAOYSA-N 7-(dimethylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)N(C)C)C=C2C(O)=O ZRISRDUHJZSFSK-UHFFFAOYSA-N 0.000 description 3
- RNNLXFYGDGETIY-UHFFFAOYSA-N 7-ethylsulfanyl-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(SCC)C=C2C(O)=O RNNLXFYGDGETIY-UHFFFAOYSA-N 0.000 description 3
- ZHWMIKHMSOYRBC-UHFFFAOYSA-N 7-ethylsulfonyl-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)CC)C=C2C(O)=O ZHWMIKHMSOYRBC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000007112 amidation reaction Methods 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- LVYXPIJZDUZGKR-UHFFFAOYSA-N n-[(1-methylpyrrolidin-2-yl)methyl]-7-sulfamoyl-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound CN1CCCC1CNC(=O)C1=CC(S(N)(=O)=O)=CC2=C1OCCO2 LVYXPIJZDUZGKR-UHFFFAOYSA-N 0.000 description 3
- 231100000957 no side effect Toxicity 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 2
- VCLSWKVAHAJSFL-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=CC=C2C(=O)O VCLSWKVAHAJSFL-UHFFFAOYSA-N 0.000 description 2
- ROYHHSBEJWIRFN-UHFFFAOYSA-N 2-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound C1=CC=C(C(N)=O)C2=C1OC(S(=O)(=O)NC)CO2 ROYHHSBEJWIRFN-UHFFFAOYSA-N 0.000 description 2
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 2
- CJPGSUPNJOCTCY-UHFFFAOYSA-N 7-(diethylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)N(CC)CC)C=C2C(O)=O CJPGSUPNJOCTCY-UHFFFAOYSA-N 0.000 description 2
- JTKAQKREMDVCLQ-UHFFFAOYSA-N 7-(dimethylsulfamoyl)-n-[(1-methylpyrrolidin-2-yl)methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound C=1C(S(=O)(=O)N(C)C)=CC=2OCCOC=2C=1C(=O)NCC1CCCN1C JTKAQKREMDVCLQ-UHFFFAOYSA-N 0.000 description 2
- NQEQVGJQJCYZNI-UHFFFAOYSA-N 7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)NC)C=C2C(O)=O NQEQVGJQJCYZNI-UHFFFAOYSA-N 0.000 description 2
- YHFLGEVINDZKFY-UHFFFAOYSA-N 7-ethylsulfonyl-n-[(1-methylpyrrolidin-2-yl)methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound C=1C(S(=O)(=O)CC)=CC=2OCCOC=2C=1C(=O)NCC1CCCN1C YHFLGEVINDZKFY-UHFFFAOYSA-N 0.000 description 2
- GPKDBCCYRICYKP-UHFFFAOYSA-N 7-sulfamoyl-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S(=O)(=O)N)C=C2C(O)=O GPKDBCCYRICYKP-UHFFFAOYSA-N 0.000 description 2
- ICGQFSSFYCENOY-UHFFFAOYSA-N 7-sulfanyl-2,3-dihydro-1,4-benzodioxine-5-carboxylic acid Chemical compound O1CCOC2=C1C=C(S)C=C2C(=O)O ICGQFSSFYCENOY-UHFFFAOYSA-N 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- KIWBPDUYBMNFTB-UHFFFAOYSA-N Ethyl hydrogen sulfate Chemical compound CCOS(O)(=O)=O KIWBPDUYBMNFTB-UHFFFAOYSA-N 0.000 description 2
- 206010060800 Hot flush Diseases 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 230000003474 anti-emetic effect Effects 0.000 description 2
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 description 2
- 229960004046 apomorphine Drugs 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 2
- 201000003146 cystitis Diseases 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000002474 experimental method Methods 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- UAMRSLPXDICKQF-UHFFFAOYSA-N methyl 7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxylate Chemical compound O1CCOC2=C1C=C(S(=O)(=O)NC)C=C2C(=O)OC UAMRSLPXDICKQF-UHFFFAOYSA-N 0.000 description 2
- GNQRWGKVRSPWSM-UHFFFAOYSA-N n-(1-cyclohexylpyrrolidin-3-yl)-7-(methylsulfamoyl)-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound C=1C(S(=O)(=O)NC)=CC=2OCCOC=2C=1C(=O)NC(C1)CCN1C1CCCCC1 GNQRWGKVRSPWSM-UHFFFAOYSA-N 0.000 description 2
- LLANSHIYQPLIKH-UHFFFAOYSA-N n-[(1-ethylpyrrolidin-2-yl)methyl]-7-sulfamoyl-2,3-dihydro-1,4-benzodioxine-5-carboxamide Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(N)(=O)=O)=CC2=C1OCCO2 LLANSHIYQPLIKH-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 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
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- OEYAFMGVIFWPQI-UHFFFAOYSA-N (1-benzylpyrrolidin-2-yl)methanamine Chemical compound NCC1CCCN1CC1=CC=CC=C1 OEYAFMGVIFWPQI-UHFFFAOYSA-N 0.000 description 1
- CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical class C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
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- Neurology (AREA)
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- Oil, Petroleum & Natural Gas (AREA)
- Psychiatry (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR7623835A FR2360305A1 (fr) | 1976-08-04 | 1976-08-04 | Nouveaux 2,3-alkylene bis (oxy)benzamides substitues, leurs derives et leurs procedes de preparation |
DE19772734270 DE2734270A1 (de) | 1976-08-04 | 1977-07-29 | Substituierte 2,3-alkylen-bis(oxy) benzamide, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
GB32117/77A GB1571447A (en) | 1976-08-04 | 1977-08-01 | Substituted 2,3-alkyleneduoxybenzamides |
JP9405677A JPS5318570A (en) | 1976-08-04 | 1977-08-04 | Novel substituted 2*33alkylenebis*oxy*benzamides* thier preparation and medical agent containing same as active ingredient |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR7623835A FR2360305A1 (fr) | 1976-08-04 | 1976-08-04 | Nouveaux 2,3-alkylene bis (oxy)benzamides substitues, leurs derives et leurs procedes de preparation |
DE19772734270 DE2734270A1 (de) | 1976-08-04 | 1977-07-29 | Substituierte 2,3-alkylen-bis(oxy) benzamide, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
Publications (2)
Publication Number | Publication Date |
---|---|
DE2734270A1 DE2734270A1 (de) | 1978-02-16 |
DE2734270C2 true DE2734270C2 (en, 2012) | 1990-06-21 |
Family
ID=52850786
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19772734270 Granted DE2734270A1 (de) | 1976-08-04 | 1977-07-29 | Substituierte 2,3-alkylen-bis(oxy) benzamide, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
Country Status (4)
Country | Link |
---|---|
JP (1) | JPS5318570A (en, 2012) |
DE (1) | DE2734270A1 (en, 2012) |
FR (1) | FR2360305A1 (en, 2012) |
GB (1) | GB1571447A (en, 2012) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE8503055D0 (sv) * | 1985-06-19 | 1985-06-19 | Astra Laekemedel Ab | Piperonylcarboxamido derivatives |
FR2586018B1 (fr) * | 1985-08-12 | 1988-03-25 | Ile De France | Nouveau benzodioxepanne, son procede de synthese et ses applications en therapeutique |
US5374637A (en) * | 1989-03-22 | 1994-12-20 | Janssen Pharmaceutica N.V. | N-(3-hydroxy-4-piperidinyl)(dihydrobenzofuran, dihydro-2H-benzopyran or dihydrobenzodioxin)carboxamide derivatives |
GB9027098D0 (en) * | 1990-12-13 | 1991-02-06 | Beecham Group Plc | Pharmaceuticals |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1220056A (en) * | 1967-02-21 | 1971-01-20 | Fisons Pest Control Ltd | Substituted benzodioxoles |
-
1976
- 1976-08-04 FR FR7623835A patent/FR2360305A1/fr active Granted
-
1977
- 1977-07-29 DE DE19772734270 patent/DE2734270A1/de active Granted
- 1977-08-01 GB GB32117/77A patent/GB1571447A/en not_active Expired
- 1977-08-04 JP JP9405677A patent/JPS5318570A/ja active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS5318570A (en) | 1978-02-20 |
GB1571447A (en) | 1980-07-16 |
FR2360305B1 (en, 2012) | 1980-04-18 |
FR2360305A1 (fr) | 1978-03-03 |
DE2734270A1 (de) | 1978-02-16 |
JPS6117832B2 (en, 2012) | 1986-05-09 |
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