PT77281B - Process for preparing n-formyl and n-hydroxymethyl-3-phenoxy-1-azetidinecarboxamides and of pharmaceutical compositions containing the same - Google Patents
Process for preparing n-formyl and n-hydroxymethyl-3-phenoxy-1-azetidinecarboxamides and of pharmaceutical compositions containing the same Download PDFInfo
- Publication number
- PT77281B PT77281B PT77281A PT7728183A PT77281B PT 77281 B PT77281 B PT 77281B PT 77281 A PT77281 A PT 77281A PT 7728183 A PT7728183 A PT 7728183A PT 77281 B PT77281 B PT 77281B
- Authority
- PT
- Portugal
- Prior art keywords
- phenoxy
- azetidinecarboxamide
- trifluoromethyl
- formyl
- preparation
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims 2
- 238000004519 manufacturing process Methods 0.000 title 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 19
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims abstract 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 37
- 238000002360 preparation method Methods 0.000 claims description 35
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 21
- 239000004480 active ingredient Substances 0.000 claims description 16
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 10
- 125000005518 carboxamido group Chemical group 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 6
- LYUPJHVGLFETDG-UHFFFAOYSA-N 1-phenylbutan-2-ol Chemical compound CCC(O)CC1=CC=CC=C1 LYUPJHVGLFETDG-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 235000019253 formic acid Nutrition 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- LIAILJLSVRAGSM-UHFFFAOYSA-N dezinamide Chemical compound C1N(C(=O)N)CC1OC1=CC=CC(C(F)(F)F)=C1 LIAILJLSVRAGSM-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- LHBPEPKZFCPYBQ-UHFFFAOYSA-N n-formyl-3-[3-(trifluoromethyl)phenoxy]azetidine-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC(OC2CN(C2)C(=O)NC=O)=C1 LHBPEPKZFCPYBQ-UHFFFAOYSA-N 0.000 claims 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims 2
- 239000003153 chemical reaction reagent Substances 0.000 claims 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims 1
- WPCOVQFDFBZJFV-UHFFFAOYSA-N n-(hydroxymethyl)-3-[3-(trifluoromethyl)phenoxy]azetidine-1-carboxamide Chemical compound C1N(C(=O)NCO)CC1OC1=CC=CC(C(F)(F)F)=C1 WPCOVQFDFBZJFV-UHFFFAOYSA-N 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims 1
- 230000001773 anti-convulsant effect Effects 0.000 abstract description 9
- 239000001961 anticonvulsive agent Substances 0.000 abstract description 7
- 229960003965 antiepileptics Drugs 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- 239000000203 mixture Substances 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 17
- -1 hettyl Chemical group 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 229920002472 Starch Polymers 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 239000008107 starch Substances 0.000 description 9
- 235000019698 starch Nutrition 0.000 description 9
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 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 7
- 239000008101 lactose Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 235000013339 cereals Nutrition 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000012265 solid product Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
- 235000013539 calcium stearate Nutrition 0.000 description 3
- 239000008116 calcium stearate Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 206010015037 epilepsy Diseases 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- FMGRHOICFABCBX-UHFFFAOYSA-N 3-[2-(trifluoromethyl)phenoxy]azetidine-1-carboxamide Chemical compound C1N(C(=O)N)CC1OC1=CC=CC=C1C(F)(F)F FMGRHOICFABCBX-UHFFFAOYSA-N 0.000 description 2
- XQHOIPJEWVQKGA-UHFFFAOYSA-N 3-phenoxyazetidine-1-carboxamide Chemical class C1N(C(=O)N)CC1OC1=CC=CC=C1 XQHOIPJEWVQKGA-UHFFFAOYSA-N 0.000 description 2
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 2
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 2
- 208000034308 Grand mal convulsion Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 206010034759 Petit mal epilepsy Diseases 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 240000006394 Sorghum bicolor Species 0.000 description 2
- 235000011684 Sorghum saccharatum Nutrition 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 235000009430 Thespesia populnea Nutrition 0.000 description 2
- 208000006633 Tonic-Clonic Epilepsy Diseases 0.000 description 2
- 208000003554 absence epilepsy Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 2
- 229940038472 dicalcium phosphate Drugs 0.000 description 2
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 2
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 201000002933 epilepsy with generalized tonic-clonic seizures Diseases 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- KMYZVCLQDUXABD-UHFFFAOYSA-N n-(hydroxymethyl)-3-phenoxyazetidine-1-carboxamide Chemical compound C1N(C(=O)NCO)CC1OC1=CC=CC=C1 KMYZVCLQDUXABD-UHFFFAOYSA-N 0.000 description 2
- CMUOJBJRZUHRMU-UHFFFAOYSA-N nitrourea Chemical compound NC(=O)N[N+]([O-])=O CMUOJBJRZUHRMU-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000007916 tablet composition Substances 0.000 description 2
- DILWWMFEHWWBCX-UHFFFAOYSA-N 1-(1-phenylethyl)azetidin-3-ol Chemical compound C=1C=CC=CC=1C(C)N1CC(O)C1 DILWWMFEHWWBCX-UHFFFAOYSA-N 0.000 description 1
- GLAMCKIBNCIMFW-UHFFFAOYSA-N 1-benzhydryl-3-phenoxyazetidine Chemical compound C1C(OC=2C=CC=CC=2)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 GLAMCKIBNCIMFW-UHFFFAOYSA-N 0.000 description 1
- VZHJIJZEOCBKRA-UHFFFAOYSA-N 1-chloro-3-fluorobenzene Chemical compound FC1=CC=CC(Cl)=C1 VZHJIJZEOCBKRA-UHFFFAOYSA-N 0.000 description 1
- UNNNAIWPDLRVRN-UHFFFAOYSA-N 1-fluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC=C(C(F)(F)F)C=C1 UNNNAIWPDLRVRN-UHFFFAOYSA-N 0.000 description 1
- HKBIOKXLBAIKTJ-UHFFFAOYSA-N 3-(3-fluorophenoxy)-n-(hydroxymethyl)azetidine-1-carboxamide Chemical compound C1N(C(=O)NCO)CC1OC1=CC=CC(F)=C1 HKBIOKXLBAIKTJ-UHFFFAOYSA-N 0.000 description 1
- XNSJSWJANFJVQI-UHFFFAOYSA-N 3-(3-fluorophenoxy)azetidine-1-carboxamide Chemical compound C1N(C(=O)N)CC1OC1=CC=CC(F)=C1 XNSJSWJANFJVQI-UHFFFAOYSA-N 0.000 description 1
- QRHBRUDGTZWRJB-UHFFFAOYSA-N 3-(3-methoxyphenoxy)azetidine Chemical compound COC1=CC=CC(OC2CNC2)=C1 QRHBRUDGTZWRJB-UHFFFAOYSA-N 0.000 description 1
- JBYYBRKRSBFVSE-UHFFFAOYSA-N 3-(3-methylphenoxy)azetidine Chemical compound CC1=CC=CC(OC2CNC2)=C1 JBYYBRKRSBFVSE-UHFFFAOYSA-N 0.000 description 1
- BRAURHKCYODXSQ-UHFFFAOYSA-N 3-(4-methoxyphenoxy)azetidine Chemical compound C1=CC(OC)=CC=C1OC1CNC1 BRAURHKCYODXSQ-UHFFFAOYSA-N 0.000 description 1
- CCXGQYXFUVSJEW-UHFFFAOYSA-N 3-(azetidin-3-yloxy)benzamide Chemical compound NC(=O)C1=CC=CC(OC2CNC2)=C1 CCXGQYXFUVSJEW-UHFFFAOYSA-N 0.000 description 1
- UMRYPVYCXBBOJV-UHFFFAOYSA-N 3-[2-(trifluoromethyl)phenoxy]azetidine Chemical compound FC(F)(F)C1=CC=CC=C1OC1CNC1 UMRYPVYCXBBOJV-UHFFFAOYSA-N 0.000 description 1
- ADXWWNMHZFPXKW-UHFFFAOYSA-N 3-[3-(trifluoromethyl)phenoxy]azetidine Chemical compound FC(F)(F)C1=CC=CC(OC2CNC2)=C1 ADXWWNMHZFPXKW-UHFFFAOYSA-N 0.000 description 1
- BGNVRWKCNDRXDE-UHFFFAOYSA-N 3-[4-(trifluoromethyl)phenoxy]azetidine-1-carboxamide Chemical compound C1N(C(=O)N)CC1OC1=CC=C(C(F)(F)F)C=C1 BGNVRWKCNDRXDE-UHFFFAOYSA-N 0.000 description 1
- CCDAHKDEKOTDGR-UHFFFAOYSA-N 3-phenoxyazetidine Chemical compound C1NCC1OC1=CC=CC=C1 CCDAHKDEKOTDGR-UHFFFAOYSA-N 0.000 description 1
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- UOWHCAKKYIRMSX-UHFFFAOYSA-N [N].C1CNC1 Chemical group [N].C1CNC1 UOWHCAKKYIRMSX-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
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- CECGBBNIUDXSHK-UHFFFAOYSA-N benzamide;oxalic acid Chemical compound OC(=O)C(O)=O.NC(=O)C1=CC=CC=C1 CECGBBNIUDXSHK-UHFFFAOYSA-N 0.000 description 1
- BMHBMLLQKJESDS-UHFFFAOYSA-N benzene;formaldehyde Chemical compound O=C.C1=CC=CC=C1 BMHBMLLQKJESDS-UHFFFAOYSA-N 0.000 description 1
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000004432 carbon atom Chemical group C* 0.000 description 1
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- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- PHRZTXWNFAEVIA-UHFFFAOYSA-N hydroxylamine;potassium Chemical compound [K].ON PHRZTXWNFAEVIA-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 238000012986 modification Methods 0.000 description 1
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- CNGQLUQTCJBZOS-UHFFFAOYSA-N n-(hydroxymethyl)-3-[2-(trifluoromethyl)phenoxy]azetidine-1-carboxamide Chemical compound C1N(C(=O)NCO)CC1OC1=CC=CC=C1C(F)(F)F CNGQLUQTCJBZOS-UHFFFAOYSA-N 0.000 description 1
- MNQOPPDTVHYCEZ-UHFFFAOYSA-N n-(hydroxymethyl)formamide Chemical compound OCNC=O MNQOPPDTVHYCEZ-UHFFFAOYSA-N 0.000 description 1
- GJBJMWGQFCIGGJ-UHFFFAOYSA-N n-formyl-3-[2-(trifluoromethyl)phenoxy]azetidine-1-carboxamide Chemical compound FC(F)(F)C1=CC=CC=C1OC1CN(C(=O)NC=O)C1 GJBJMWGQFCIGGJ-UHFFFAOYSA-N 0.000 description 1
- YNPHLUWNKSFGBY-UHFFFAOYSA-N n-formyl-3-phenoxyazetidine-1-carboxamide Chemical compound C1N(C(=O)NC=O)CC1OC1=CC=CC=C1 YNPHLUWNKSFGBY-UHFFFAOYSA-N 0.000 description 1
- AIDQCFHFXWPAFG-UHFFFAOYSA-N n-formylformamide Chemical compound O=CNC=O AIDQCFHFXWPAFG-UHFFFAOYSA-N 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
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 229960005152 pentetrazol Drugs 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/414,101 US4505907A (en) | 1982-09-02 | 1982-09-02 | N-Formyl and N-hydroxymethyl-3-phenoxy-1-azetidinecarboxamides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PT77281A PT77281A (en) | 1983-10-01 |
| PT77281B true PT77281B (en) | 1986-02-04 |
Family
ID=23639965
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT77281A PT77281B (en) | 1982-09-02 | 1983-09-01 | Process for preparing n-formyl and n-hydroxymethyl-3-phenoxy-1-azetidinecarboxamides and of pharmaceutical compositions containing the same |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US4505907A (en, 2012) |
| EP (1) | EP0102740B1 (en, 2012) |
| JP (1) | JPS601161A (en, 2012) |
| KR (1) | KR900005131B1 (en, 2012) |
| AU (1) | AU553472B2 (en, 2012) |
| CA (1) | CA1185983A (en, 2012) |
| CS (1) | CS240974B2 (en, 2012) |
| DE (1) | DE3367385D1 (en, 2012) |
| DK (1) | DK166297C (en, 2012) |
| EG (1) | EG16473A (en, 2012) |
| ES (2) | ES523194A0 (en, 2012) |
| FI (1) | FI77226C (en, 2012) |
| GR (1) | GR79337B (en, 2012) |
| HK (1) | HK47587A (en, 2012) |
| HU (1) | HU189740B (en, 2012) |
| IE (1) | IE55770B1 (en, 2012) |
| IL (1) | IL68743A0 (en, 2012) |
| IN (1) | IN161222B (en, 2012) |
| NO (1) | NO157977C (en, 2012) |
| NZ (1) | NZ205448A (en, 2012) |
| PH (1) | PH20572A (en, 2012) |
| PL (2) | PL142643B1 (en, 2012) |
| PT (1) | PT77281B (en, 2012) |
| YU (1) | YU44747B (en, 2012) |
| ZA (1) | ZA834410B (en, 2012) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4571393A (en) * | 1982-08-19 | 1986-02-18 | A. H. Robins Company, Incorporated | 3-Phenoxy-1-azetidinecarboxamides |
| US4594189A (en) * | 1983-07-06 | 1986-06-10 | A. H. Robins Company, Inc. | Process for preparing 3-phenoxy-1-azetidines and carboxamide derivatives |
| ZA861210B (en) * | 1985-02-28 | 1987-10-28 | Robins Co Inc A H | 3-aryloxyazetidinecarboxamides as anticonvulsants and antiepileptics |
| US4956359A (en) * | 1985-02-28 | 1990-09-11 | A. H. Robins Company, Inc. | 3-aryloxy and 3-arylthioazetidinecarboxamides as anticonvulsants and antiepileptics |
| US5068231A (en) * | 1985-02-28 | 1991-11-26 | A. H. Robins Company Incorporated | Method of treating muscular tension, muscle spasticity and anxiety with 3-aryloxy and 3-arylthioazetidinecarboxamides |
| IN162808B (en, 2012) * | 1985-02-28 | 1988-07-09 | Robins Co Inc A H | |
| IE58943B1 (en) * | 1985-02-28 | 1993-12-01 | Robins Co Inc A H | 3-Aryloxy-azetidine-carboxamides |
| US5130309A (en) * | 1991-04-12 | 1992-07-14 | A. H. Robins Company, Incorporated | Aryloxy and aryloxyalklazetidines as antiarrhythmic and anticonvulsant agents |
| JP3178922B2 (ja) * | 1992-12-03 | 2001-06-25 | 小松ゼノア株式会社 | エンジンの吸気装置 |
| ES2181387T3 (es) | 1998-01-23 | 2003-02-16 | Vernalis Res Ltd | Derivados de azetidinocarboxamida para el tratamiento de trastornos del sistema nervioso central. |
| GB9801501D0 (en) * | 1998-01-23 | 1998-03-18 | Cerebrus Ltd | Chemical compounds - II |
| ES2207171T3 (es) | 1998-01-23 | 2004-05-16 | Vernalis Research Limited | Derivados de azetidina carboxamida para tratar trastornos del sistema nervioso central. |
| GB9917386D0 (en) * | 1999-07-23 | 1999-09-22 | Cerebrus Ltd | Chemical compounds-II |
| GB9917385D0 (en) * | 1999-07-23 | 1999-09-22 | Cerebrus Ltd | Chemical compounds-I |
| EP2202223B1 (en) * | 2007-10-18 | 2017-01-25 | Takeda Pharmaceutical Company Limited | Heterocyclic compound as blood rbp4 lowering agent |
| US10365007B2 (en) | 2014-09-30 | 2019-07-30 | Fujitsu General Limited | Ceiling-embedded air conditioner |
| JP6504349B2 (ja) | 2015-03-31 | 2019-04-24 | 株式会社富士通ゼネラル | 天井埋込型空気調和機 |
| US10288302B2 (en) | 2015-03-31 | 2019-05-14 | Fujitsu General Limited | Ceiling-embedded air conditioner with airflow guide vane |
| JP6516095B2 (ja) | 2015-04-27 | 2019-05-22 | 株式会社富士通ゼネラル | 天井埋込型空気調和機 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB872447A (en) * | 1958-12-23 | 1961-07-12 | Lepetit Spa | 1-carbamyl-3-substituted azetidines |
| DE2053333A1 (de) * | 1970-10-30 | 1972-05-04 | Farbenfabriken Bayer Ag, 5090 Lever Kusen | Herbizide Mittel |
| US4031221A (en) * | 1974-06-17 | 1977-06-21 | American Hoechst Corporation | Method of treating pain and hypertension |
| US4379151A (en) * | 1978-03-14 | 1983-04-05 | A. H. Robins Company, Inc. | 3-Phenoxyazetidines for anorexigenic activity |
| US4226861A (en) * | 1978-04-18 | 1980-10-07 | A. H. Robins Company, Inc. | N-Lower-alkyl 3-phenoxy-1-azetidinecarboxamides |
-
1982
- 1982-09-02 US US06/414,101 patent/US4505907A/en not_active Expired - Lifetime
-
1983
- 1983-05-17 AU AU14598/83A patent/AU553472B2/en not_active Ceased
- 1983-05-20 IL IL68743A patent/IL68743A0/xx not_active IP Right Cessation
- 1983-06-13 ES ES523194A patent/ES523194A0/es active Granted
- 1983-06-15 EG EG363/83A patent/EG16473A/xx active
- 1983-06-16 ZA ZA834410A patent/ZA834410B/xx unknown
- 1983-07-05 GR GR71865A patent/GR79337B/el unknown
- 1983-07-15 IE IE1652/83A patent/IE55770B1/en not_active IP Right Cessation
- 1983-07-27 EP EP83304349A patent/EP0102740B1/en not_active Expired
- 1983-07-27 DE DE8383304349T patent/DE3367385D1/de not_active Expired
- 1983-08-02 JP JP58141816A patent/JPS601161A/ja active Granted
- 1983-08-16 YU YU1704/83A patent/YU44747B/xx unknown
- 1983-08-23 CS CS836141A patent/CS240974B2/cs unknown
- 1983-08-25 CA CA000435387A patent/CA1185983A/en not_active Expired
- 1983-08-29 PL PL1983243555A patent/PL142643B1/pl unknown
- 1983-08-29 PL PL1983261983A patent/PL145986B1/pl unknown
- 1983-08-31 KR KR1019830004080A patent/KR900005131B1/ko not_active Expired
- 1983-09-01 NO NO833135A patent/NO157977C/no unknown
- 1983-09-01 PH PH29480A patent/PH20572A/en unknown
- 1983-09-01 HU HU833053A patent/HU189740B/hu not_active IP Right Cessation
- 1983-09-01 FI FI833126A patent/FI77226C/fi not_active IP Right Cessation
- 1983-09-01 DK DK398783A patent/DK166297C/da active
- 1983-09-01 PT PT77281A patent/PT77281B/pt not_active IP Right Cessation
- 1983-09-01 NZ NZ205448A patent/NZ205448A/en unknown
- 1983-09-01 IN IN1066/CAL/83A patent/IN161222B/en unknown
-
1984
- 1984-11-15 ES ES537668A patent/ES537668A0/es active Granted
-
1987
- 1987-06-18 HK HK475/87A patent/HK47587A/xx unknown
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PC3A | Transfer or assignment |
Free format text: 921231 A.H. ROBINS COMPANY, INCORPORATED US |
|
| MM3A | Annulment or lapse |
Free format text: LAPSE DUE TO NON-PAYMENT OF FEES Effective date: 19960831 |