CA1080723A - Pharmaceutically active acetamidoxime derivatives - Google Patents
Pharmaceutically active acetamidoxime derivativesInfo
- Publication number
- CA1080723A CA1080723A CA267,918A CA267918A CA1080723A CA 1080723 A CA1080723 A CA 1080723A CA 267918 A CA267918 A CA 267918A CA 1080723 A CA1080723 A CA 1080723A
- Authority
- CA
- Canada
- Prior art keywords
- ethyl
- benzofuranyl
- methyl
- morpholino
- acetamidoxime
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical class CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 63
- -1 dimethylamino, di-n-propylamino, di-n-butylamino, pyrrolidino, morpholino Chemical group 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 239000002253 acid Substances 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 229910052801 chlorine Chemical group 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 5
- 238000007142 ring opening reaction Methods 0.000 claims description 4
- 230000001476 alcoholic effect Effects 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- JYXQXKHTALMLNI-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)-n-hydroxy-n'-(2-morpholin-4-ylethyl)ethanimidamide Chemical compound CCC=1OC2=CC=CC=C2C=1CC(NO)=NCCN1CCOCC1 JYXQXKHTALMLNI-UHFFFAOYSA-N 0.000 claims 1
- 150000007522 mineralic acids Chemical class 0.000 claims 1
- 150000007524 organic acids Chemical class 0.000 claims 1
- 230000004872 arterial blood pressure Effects 0.000 abstract description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 208000035475 disorder Diseases 0.000 abstract description 2
- 125000003277 amino group Chemical group 0.000 abstract 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 117
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- 238000001953 recrystallisation Methods 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 206010020772 Hypertension Diseases 0.000 description 16
- 241000700159 Rattus Species 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
- 239000003208 petroleum Substances 0.000 description 13
- 239000000203 mixture Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 239000012429 reaction media Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 229910001415 sodium ion Inorganic materials 0.000 description 7
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 230000003276 anti-hypertensive effect Effects 0.000 description 6
- 230000002354 daily effect Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- BIGWXAGEQONZGD-UHFFFAOYSA-N 2h-oxadiazol-5-one Chemical compound O=C1C=NNO1 BIGWXAGEQONZGD-UHFFFAOYSA-N 0.000 description 5
- TVEGBGLLZMPPOI-UHFFFAOYSA-N n'-hydroxyethanimidamide;dihydrochloride Chemical compound Cl.Cl.CC(N)=NO TVEGBGLLZMPPOI-UHFFFAOYSA-N 0.000 description 5
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 5
- YFDYEHIAUKXEDK-UHFFFAOYSA-N (n-hydroxy-c-methylcarbonimidoyl)azanium;chloride Chemical compound Cl.C\C(N)=N\O YFDYEHIAUKXEDK-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-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
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000002220 antihypertensive agent Substances 0.000 description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 230000001882 diuretic effect Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000029142 excretion Effects 0.000 description 4
- 210000003734 kidney Anatomy 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- VLWINELGTMKBKV-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)-2-methylpropanenitrile Chemical compound C1=CC=C2C(C(C)(C)C#N)=C(CC)OC2=C1 VLWINELGTMKBKV-UHFFFAOYSA-N 0.000 description 3
- UVUQVKDHNYUOJX-UHFFFAOYSA-N 2h-oxadiazol-5-one;hydrochloride Chemical compound Cl.O=C1C=NNO1 UVUQVKDHNYUOJX-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
- 229940030600 antihypertensive agent Drugs 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 230000002005 ganglioplegic effect Effects 0.000 description 3
- 230000001631 hypertensive effect Effects 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 229940017219 methyl propionate Drugs 0.000 description 3
- 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910021653 sulphate ion Inorganic materials 0.000 description 3
- 230000002889 sympathetic effect Effects 0.000 description 3
- 231100000816 toxic dose Toxicity 0.000 description 3
- 210000002700 urine Anatomy 0.000 description 3
- ISRPYPFEBBECGJ-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)propanamide Chemical compound C1=CC=C2C(C(C)C(N)=O)=C(CC)OC2=C1 ISRPYPFEBBECGJ-UHFFFAOYSA-N 0.000 description 2
- YYDJLSNJCWIFMW-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)propanenitrile Chemical compound C1=CC=C2C(C(C)C#N)=C(CC)OC2=C1 YYDJLSNJCWIFMW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- AWKBYVHZGQSXEX-UHFFFAOYSA-N C(C(=O)O)(=O)O.C(C)(N)=NO.C(C(=O)O)(=O)O.C(C(=O)O)(=O)O.C(C)(N)=NO Chemical compound C(C(=O)O)(=O)O.C(C)(N)=NO.C(C(=O)O)(=O)O.C(C(=O)O)(=O)O.C(C)(N)=NO AWKBYVHZGQSXEX-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 208000007530 Essential hypertension Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 150000002825 nitriles Chemical group 0.000 description 2
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 229910001414 potassium ion Inorganic materials 0.000 description 2
- NFXCUPVBISCOSF-UHFFFAOYSA-N propan-2-ol;dihydrochloride Chemical compound Cl.Cl.CC(C)O NFXCUPVBISCOSF-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- PEKBDPWIKMPIIL-UHFFFAOYSA-N (2-ethyl-1-benzofuran-3-yl)methyl acetate Chemical compound C1=CC=C2C(COC(C)=O)=C(CC)OC2=C1 PEKBDPWIKMPIIL-UHFFFAOYSA-N 0.000 description 1
- ORZXLVOLYLGCSV-UHFFFAOYSA-N 1-(dimethylamino)-4-methylpentan-3-one Chemical compound CC(C)C(=O)CCN(C)C ORZXLVOLYLGCSV-UHFFFAOYSA-N 0.000 description 1
- QBCLAMPIMBDBRS-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)-n'-hydroxy-2-methylpropanimidamide;hydrochloride Chemical compound Cl.C1=CC=C2C(C(C)(C)C(N)=NO)=C(CC)OC2=C1 QBCLAMPIMBDBRS-UHFFFAOYSA-N 0.000 description 1
- RPGIMPBBLNIOMU-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)-n'-hydroxybutanimidamide Chemical compound C1=CC=C2C(C(C(N)=NO)CC)=C(CC)OC2=C1 RPGIMPBBLNIOMU-UHFFFAOYSA-N 0.000 description 1
- PVWUVYBOLVWWHC-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)-n'-hydroxypropanimidamide Chemical compound C1=CC=C2C(C(C)C(N)=NO)=C(CC)OC2=C1 PVWUVYBOLVWWHC-UHFFFAOYSA-N 0.000 description 1
- PLGNFLMOLRTNKS-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)-n-hydroxy-2-methyl-n'-(2-piperidin-1-ylethyl)propanimidamide Chemical compound CCC=1OC2=CC=CC=C2C=1C(C)(C)C(NO)=NCCN1CCCCC1 PLGNFLMOLRTNKS-UHFFFAOYSA-N 0.000 description 1
- RWCHGCSLPRNFRX-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)acetonitrile Chemical compound C1=CC=C2C(CC#N)=C(CC)OC2=C1 RWCHGCSLPRNFRX-UHFFFAOYSA-N 0.000 description 1
- FCJSCJKNOCHQCU-UHFFFAOYSA-N 2-(2-ethyl-1-benzofuran-3-yl)propanoyl chloride Chemical compound C1=CC=C2C(C(C)C(Cl)=O)=C(CC)OC2=C1 FCJSCJKNOCHQCU-UHFFFAOYSA-N 0.000 description 1
- DKFBJAYTVWPIGB-UHFFFAOYSA-N 2-methyl-4-piperidin-1-ylbutan-2-ol Chemical compound CC(C)(O)CCN1CCCCC1 DKFBJAYTVWPIGB-UHFFFAOYSA-N 0.000 description 1
- FSXNKUMPZMWMMF-UHFFFAOYSA-N 4-(3-ethoxypropyl)morpholine Chemical compound CCOCCCN1CCOCC1 FSXNKUMPZMWMMF-UHFFFAOYSA-N 0.000 description 1
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- LUAMBZGJXUMNQX-UHFFFAOYSA-N C(C)(C)O.Cl.Cl.C(C)(N)=NO Chemical compound C(C)(C)O.Cl.Cl.C(C)(N)=NO LUAMBZGJXUMNQX-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- ILCIYECOGUQUSQ-UHFFFAOYSA-N Cl.Cl.C(C)(N(C)CC)=NO Chemical compound Cl.Cl.C(C)(N(C)CC)=NO ILCIYECOGUQUSQ-UHFFFAOYSA-N 0.000 description 1
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- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
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- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 1
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
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- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 241000245026 Scoliopus bigelovii Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000212342 Sium Species 0.000 description 1
- 101150007148 THI5 gene Proteins 0.000 description 1
- 241000489523 Veratrum Species 0.000 description 1
- JPKKQJKQTPNWTR-KQAYXBCTSA-N [(1r,5s)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] (2r)-3-hydroxy-2-phenylpropanoate;sulfuric acid;hydrate Chemical compound O.OS(O)(=O)=O.C1([C@H](CO)C(=O)OC2C[C@H]3CC[C@@H](C2)N3C)=CC=CC=C1.C1([C@H](CO)C(=O)OC2C[C@H]3CC[C@@H](C2)N3C)=CC=CC=C1 JPKKQJKQTPNWTR-KQAYXBCTSA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
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- 231100000403 acute toxicity Toxicity 0.000 description 1
- 210000004100 adrenal gland Anatomy 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- IANQTJSKSUMEQM-UHFFFAOYSA-N benzofuran Natural products C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 235000012467 brownies Nutrition 0.000 description 1
- JLQUFIHWVLZVTJ-UHFFFAOYSA-N carbosulfan Chemical compound CCCCN(CCCC)SN(C)C(=O)OC1=CC=CC2=C1OC(C)(C)C2 JLQUFIHWVLZVTJ-UHFFFAOYSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003457 ganglion blocking agent Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 208000015345 genetic hypertension Diseases 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- AKPUJVVHYUHGKY-UHFFFAOYSA-N hydron;propan-2-ol;chloride Chemical compound Cl.CC(C)O AKPUJVVHYUHGKY-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- JDBBTVFYDZWUFI-UHFFFAOYSA-K iron(3+) trinitrite Chemical compound [Fe+3].[O-]N=O.[O-]N=O.[O-]N=O JDBBTVFYDZWUFI-UHFFFAOYSA-K 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003801 laryngeal nerve Anatomy 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 208000012866 low blood pressure Diseases 0.000 description 1
- 201000005857 malignant hypertension Diseases 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- ALSUZWPSQNIYQI-UHFFFAOYSA-N n'-hydroxy-4-morpholin-4-ylbutanimidamide Chemical compound ON=C(N)CCCN1CCOCC1 ALSUZWPSQNIYQI-UHFFFAOYSA-N 0.000 description 1
- UUIRQFMZIGGUJL-UHFFFAOYSA-N n'-hydroxy-4-piperidin-1-ylbutanimidamide Chemical compound ON=C(N)CCCN1CCCCC1 UUIRQFMZIGGUJL-UHFFFAOYSA-N 0.000 description 1
- PGUHXFUYWIBXET-UHFFFAOYSA-N n'-hydroxyethanimidamide;trihydrochloride Chemical compound Cl.Cl.Cl.CC(N)=NO PGUHXFUYWIBXET-UHFFFAOYSA-N 0.000 description 1
- 210000004237 neck muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 210000000826 nictitating membrane Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 description 1
- 229950000494 pentamethonium bromide Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000007686 potassium Nutrition 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 229940093932 potassium hydroxide Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 206010038464 renal hypertension Diseases 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000003730 sympathetic denervation Effects 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000005289 uranyl group Chemical group 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 230000036325 urinary excretion Effects 0.000 description 1
- 229940057613 veratrum Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (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)
- Furan Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB52475/75A GB1508210A (en) | 1975-12-22 | 1975-12-22 | Benzofuran-derived amidoximes and process for preparing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1080723A true CA1080723A (en) | 1980-07-01 |
Family
ID=10464059
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA267,918A Expired CA1080723A (en) | 1975-12-22 | 1976-12-15 | Pharmaceutically active acetamidoxime derivatives |
Country Status (28)
| Country | Link |
|---|---|
| JP (1) | JPS52102268A (OSRAM) |
| AR (1) | AR212605A1 (OSRAM) |
| AT (1) | AT354430B (OSRAM) |
| AU (1) | AU503931B2 (OSRAM) |
| BE (1) | BE849430A (OSRAM) |
| CA (1) | CA1080723A (OSRAM) |
| CH (1) | CH617688A5 (OSRAM) |
| DD (1) | DD127762A5 (OSRAM) |
| DE (1) | DE2657902A1 (OSRAM) |
| DK (1) | DK577276A (OSRAM) |
| ES (1) | ES454421A1 (OSRAM) |
| FI (1) | FI60395C (OSRAM) |
| FR (1) | FR2336127A1 (OSRAM) |
| GB (1) | GB1508210A (OSRAM) |
| HU (1) | HU176557B (OSRAM) |
| IE (1) | IE44753B1 (OSRAM) |
| IT (1) | IT1123948B (OSRAM) |
| MX (1) | MX3927E (OSRAM) |
| NL (1) | NL7613753A (OSRAM) |
| NO (1) | NO144794C (OSRAM) |
| NZ (1) | NZ182809A (OSRAM) |
| OA (1) | OA05521A (OSRAM) |
| PL (1) | PL102695B1 (OSRAM) |
| PT (1) | PT65971B (OSRAM) |
| SE (1) | SE429233B (OSRAM) |
| SU (1) | SU598564A3 (OSRAM) |
| YU (1) | YU309376A (OSRAM) |
| ZA (1) | ZA767241B (OSRAM) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3398941A1 (en) * | 2017-05-03 | 2018-11-07 | AXXAM S.p.A. | Heterocyclic p2x7 antagonists |
-
1975
- 1975-12-22 GB GB52475/75A patent/GB1508210A/en not_active Expired
-
1976
- 1976-12-03 IE IE2663/76A patent/IE44753B1/en unknown
- 1976-12-06 ZA ZA767241A patent/ZA767241B/xx unknown
- 1976-12-06 NZ NZ182809A patent/NZ182809A/xx unknown
- 1976-12-10 NL NL7613753A patent/NL7613753A/xx not_active Application Discontinuation
- 1976-12-13 AR AR265814A patent/AR212605A1/es active
- 1976-12-14 AU AU20534/76A patent/AU503931B2/en not_active Expired
- 1976-12-14 FR FR7637622A patent/FR2336127A1/fr active Granted
- 1976-12-15 BE BE173280A patent/BE849430A/xx not_active IP Right Cessation
- 1976-12-15 MX MX765235U patent/MX3927E/es unknown
- 1976-12-15 CA CA267,918A patent/CA1080723A/en not_active Expired
- 1976-12-15 FI FI763604A patent/FI60395C/fi not_active IP Right Cessation
- 1976-12-15 PT PT65971A patent/PT65971B/pt unknown
- 1976-12-20 CH CH1603476A patent/CH617688A5/fr not_active IP Right Cessation
- 1976-12-20 ES ES454421A patent/ES454421A1/es not_active Expired
- 1976-12-20 YU YU03093/76A patent/YU309376A/xx unknown
- 1976-12-21 DK DK577276A patent/DK577276A/da not_active Application Discontinuation
- 1976-12-21 AT AT948476A patent/AT354430B/de not_active IP Right Cessation
- 1976-12-21 HU HU76LA901A patent/HU176557B/hu unknown
- 1976-12-21 SU SU762430683A patent/SU598564A3/ru active
- 1976-12-21 PL PL1976194589A patent/PL102695B1/pl unknown
- 1976-12-21 NO NO76764332A patent/NO144794C/no unknown
- 1976-12-21 DE DE19762657902 patent/DE2657902A1/de not_active Withdrawn
- 1976-12-21 IT IT7630679A patent/IT1123948B/it active
- 1976-12-21 SE SE7614368A patent/SE429233B/xx unknown
- 1976-12-22 JP JP15558976A patent/JPS52102268A/ja active Pending
- 1976-12-22 DD DD7600196548A patent/DD127762A5/xx unknown
- 1976-12-22 OA OA56023A patent/OA05521A/xx unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |