NO811667L - Fremgangsmaate ved fremstilling av substituerte pyrazinyl-1,2,4-oxadiazoler - Google Patents
Fremgangsmaate ved fremstilling av substituerte pyrazinyl-1,2,4-oxadiazolerInfo
- Publication number
- NO811667L NO811667L NO811667A NO811667A NO811667L NO 811667 L NO811667 L NO 811667L NO 811667 A NO811667 A NO 811667A NO 811667 A NO811667 A NO 811667A NO 811667 L NO811667 L NO 811667L
- Authority
- NO
- Norway
- Prior art keywords
- carbon atoms
- lower alkyl
- hydrogen
- formula
- amino
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 29
- 150000001875 compounds Chemical class 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 3
- 150000001350 alkyl halides Chemical class 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 150000001805 chlorine compounds Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 150000003839 salts Chemical group 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- -1 alkali metal cation Chemical class 0.000 description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- 239000002934 diuretic Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 229940030606 diuretics Drugs 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- BOGXMMNLVXIRCE-UHFFFAOYSA-N 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloro-6-n,6-n-dimethylpyrazine-2,6-diamine Chemical compound N1=C(Cl)C(N(C)C)=NC(N)=C1C1=NC(N)=NO1 BOGXMMNLVXIRCE-UHFFFAOYSA-N 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 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 5
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 230000002077 kaliuretic effect Effects 0.000 description 4
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- GJLPISUGPIFCFQ-UHFFFAOYSA-N 3-(3-amino-1,2,4-oxadiazol-5-yl)-5-chloropyrazine-2,6-diamine Chemical compound NC1=NOC(C=2C(=NC(N)=C(Cl)N=2)N)=N1 GJLPISUGPIFCFQ-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 230000001882 diuretic effect Effects 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
- 229960002003 hydrochlorothiazide Drugs 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- LUQGFLSFFWYKBL-UHFFFAOYSA-N 3,5-diamino-6-chloro-n-[(2-oxohydrazinyl)methylidene]pyrazine-2-carboxamide Chemical compound NC1=NC(N)=C(C(=O)N=CN=NO)N=C1Cl LUQGFLSFFWYKBL-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000000538 analytical sample Substances 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 235000011148 calcium chloride Nutrition 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- OUYYNZDOJHSQBW-UHFFFAOYSA-N cyanomethanimidamide Chemical compound NC(=N)C#N OUYYNZDOJHSQBW-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 1
- PRKWVSHZYDOZLP-UHFFFAOYSA-N 2-[(6,7-dichloro-2-methyl-1-oxo-2-phenyl-3h-inden-5-yl)oxy]acetic acid Chemical compound C1C2=CC(OCC(O)=O)=C(Cl)C(Cl)=C2C(=O)C1(C)C1=CC=CC=C1 PRKWVSHZYDOZLP-UHFFFAOYSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- OBEXLEJFAXGHNA-UHFFFAOYSA-N 3-(3-amino-2-methyl-1,2,4-oxadiazol-2-ium-5-yl)-5-chloro-6-n,6-n-dimethylpyrazine-2,6-diamine;iodide Chemical compound [I-].N1=C(Cl)C(N(C)C)=NC(N)=C1C1=NC(N)=[N+](C)O1 OBEXLEJFAXGHNA-UHFFFAOYSA-N 0.000 description 1
- HCAMWEDSKUNLAF-UHFFFAOYSA-N 3-(3-amino-2-methyl-1,2,4-oxadiazol-2-ium-5-yl)-5-chloropyrazine-2,6-diamine;iodide Chemical compound [I-].NC1=[N+](C)OC(C=2C(=NC(N)=C(Cl)N=2)N)=N1 HCAMWEDSKUNLAF-UHFFFAOYSA-N 0.000 description 1
- AFDKXWRUGFKXGE-UHFFFAOYSA-N 3-amino-6-chloro-n'-cyano-5-(dimethylamino)pyrazine-2-carboximidamide Chemical compound CN(C)C1=NC(N)=C(C(=N)NC#N)N=C1Cl AFDKXWRUGFKXGE-UHFFFAOYSA-N 0.000 description 1
- YOXZGZLYFDUDKG-UHFFFAOYSA-N 3-chloro-5-[3-(dimethylamino)-1,2,4-oxadiazol-5-yl]pyrazine-2,6-diamine Chemical compound CN(C)C1=NOC(C=2C(=NC(N)=C(Cl)N=2)N)=N1 YOXZGZLYFDUDKG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010014418 Electrolyte imbalance Diseases 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- WFBHRSAKANVBKH-UHFFFAOYSA-N N-hydroxyguanidine Chemical compound NC(=N)NO WFBHRSAKANVBKH-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- GMABGUNFNNTKKN-UHFFFAOYSA-N [5-(3,5-diamino-6-chloropyrazin-2-yl)-2-methyl-1,2,4-oxadiazol-3-ylidene]-dimethylazanium;iodide Chemical compound [I-].C[N+](C)=C1N(C)OC(C=2C(=NC(N)=C(Cl)N=2)N)=N1 GMABGUNFNNTKKN-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000003337 anti-kaliuretic effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 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
- 229960004064 bumetanide Drugs 0.000 description 1
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960002155 chlorothiazide Drugs 0.000 description 1
- 229960001523 chlortalidone Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- PMSVVUSIPKHUMT-UHFFFAOYSA-N cyanopyrazine Chemical compound N#CC1=CN=CC=N1 PMSVVUSIPKHUMT-UHFFFAOYSA-N 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
- 229960003199 etacrynic acid Drugs 0.000 description 1
- OUZWUKMCLIBBOG-UHFFFAOYSA-N ethoxzolamide Chemical compound CCOC1=CC=C2N=C(S(N)(=O)=O)SC2=C1 OUZWUKMCLIBBOG-UHFFFAOYSA-N 0.000 description 1
- 229950005098 ethoxzolamide Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229950009607 indacrinone Drugs 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- FLOSMHQXBMRNHR-DAXSKMNVSA-N methazolamide Chemical compound CC(=O)\N=C1/SC(S(N)(=O)=O)=NN1C FLOSMHQXBMRNHR-DAXSKMNVSA-N 0.000 description 1
- 229960004083 methazolamide Drugs 0.000 description 1
- 229960002817 metolazone Drugs 0.000 description 1
- AQCHWTWZEMGIFD-UHFFFAOYSA-N metolazone Chemical compound CC1NC2=CC(Cl)=C(S(N)(=O)=O)C=C2C(=O)N1C1=CC=CC=C1C AQCHWTWZEMGIFD-UHFFFAOYSA-N 0.000 description 1
- RLWRMIYXDPXIEX-UHFFFAOYSA-N muzolimine Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(C)N1N=C(N)CC1=O RLWRMIYXDPXIEX-UHFFFAOYSA-N 0.000 description 1
- 229960001788 muzolimine Drugs 0.000 description 1
- 230000001452 natriuretic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000010408 sweeping Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000003424 uricosuric effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/151,494 US4309540A (en) | 1980-05-19 | 1980-05-19 | Substituted pyrazinyl-1,2,4-oxadiazoles |
| US06/244,509 US4362724A (en) | 1980-05-19 | 1981-03-16 | Method of treating edema and hypertension and pharmaceutical composition therefor in which the active ingredient comprises a novel substituted pyrazinyl-1,2,4-oxadiazole and a kaliuretic diuretic |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO811667L true NO811667L (no) | 1981-11-20 |
Family
ID=26848697
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO811667A NO811667L (no) | 1980-05-19 | 1981-05-15 | Fremgangsmaate ved fremstilling av substituerte pyrazinyl-1,2,4-oxadiazoler |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4362724A (es) |
| EP (1) | EP0040422B1 (es) |
| AU (1) | AU536493B2 (es) |
| DE (1) | DE3161767D1 (es) |
| DK (1) | DK214681A (es) |
| ES (1) | ES502282A0 (es) |
| FI (1) | FI811421L (es) |
| GR (1) | GR74903B (es) |
| IE (1) | IE51288B1 (es) |
| NO (1) | NO811667L (es) |
| NZ (1) | NZ197055A (es) |
| PT (1) | PT73016B (es) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6858614B2 (en) * | 2002-02-19 | 2005-02-22 | Parion Sciences, Inc. | Phenolic guanidine sodium channel blockers |
| US6858615B2 (en) * | 2002-02-19 | 2005-02-22 | Parion Sciences, Inc. | Phenyl guanidine sodium channel blockers |
| US6903105B2 (en) | 2003-02-19 | 2005-06-07 | Parion Sciences, Inc. | Sodium channel blockers |
| US7745442B2 (en) | 2003-08-20 | 2010-06-29 | Parion Sciences, Inc. | Methods of reducing risk of infection from pathogens |
| AR086745A1 (es) | 2011-06-27 | 2014-01-22 | Parion Sciences Inc | 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida |
| AU2013363218B2 (en) | 2012-12-17 | 2018-03-15 | Parion Sciences, Inc. | Chloro-pyrazine carboxamide derivatives useful for the treatment of diseases favoured by insufficient mucosal hydration |
| KR20150095870A (ko) | 2012-12-17 | 2015-08-21 | 패리온 사이언스 인코퍼레이티드 | 3,5-디아미노-6-클로로-n-(n-(4-페닐부틸)카르밤이미도일)피라진-2-카르복스아미드 화합물 |
| US9102633B2 (en) | 2013-12-13 | 2015-08-11 | Parion Sciences, Inc. | Arylalkyl- and aryloxyalkyl-substituted epithelial sodium channel blocking compounds |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL299931A (es) * | 1962-10-30 | |||
| MC641A1 (fr) * | 1967-03-08 | 1967-12-05 | Mauvernay Roland Yves | Nouveaux composés chimiques et procédé pour leur préparation |
| US4196292A (en) * | 1977-06-29 | 1980-04-01 | Merck & Co., Inc. | 6-Substituted amiloride derivatives |
| EP0009054A1 (en) * | 1978-09-19 | 1980-04-02 | Merck & Co. Inc. | N-Pyrazinecarbonyl-N'-substituted-sulfamoyl-guanidine and processes for preparing same |
-
1981
- 1981-03-16 US US06/244,509 patent/US4362724A/en not_active Expired - Fee Related
- 1981-05-06 AU AU70180/81A patent/AU536493B2/en not_active Ceased
- 1981-05-08 FI FI811421A patent/FI811421L/fi not_active Application Discontinuation
- 1981-05-11 NZ NZ197055A patent/NZ197055A/en unknown
- 1981-05-11 PT PT73016A patent/PT73016B/pt unknown
- 1981-05-14 DK DK214681A patent/DK214681A/da not_active Application Discontinuation
- 1981-05-14 GR GR64954A patent/GR74903B/el unknown
- 1981-05-15 NO NO811667A patent/NO811667L/no unknown
- 1981-05-18 DE DE8181103800T patent/DE3161767D1/de not_active Expired
- 1981-05-18 IE IE1102/81A patent/IE51288B1/en unknown
- 1981-05-18 EP EP81103800A patent/EP0040422B1/en not_active Expired
- 1981-05-18 ES ES502282A patent/ES502282A0/es active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| ES8207528A1 (es) | 1982-10-01 |
| PT73016B (en) | 1983-08-08 |
| NZ197055A (en) | 1984-07-31 |
| US4362724A (en) | 1982-12-07 |
| IE811102L (en) | 1981-11-19 |
| IE51288B1 (en) | 1986-11-26 |
| PT73016A (en) | 1981-06-01 |
| AU536493B2 (en) | 1984-05-10 |
| GR74903B (es) | 1984-07-12 |
| EP0040422B1 (en) | 1983-12-28 |
| ES502282A0 (es) | 1982-10-01 |
| DE3161767D1 (en) | 1984-02-02 |
| DK214681A (da) | 1981-11-20 |
| AU7018081A (en) | 1981-11-26 |
| FI811421L (fi) | 1981-11-20 |
| EP0040422A1 (en) | 1981-11-25 |
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