SE437518B - Nya derivat av 4-amino-2-(piperazin-1-yl eller homopiperazin-1-yl)kinazolin, sett att framstella denna och farmaceutisk beredning for reglering av det kardiovaskulera systemet - Google Patents
Nya derivat av 4-amino-2-(piperazin-1-yl eller homopiperazin-1-yl)kinazolin, sett att framstella denna och farmaceutisk beredning for reglering av det kardiovaskulera systemetInfo
- Publication number
- SE437518B SE437518B SE7811382A SE7811382A SE437518B SE 437518 B SE437518 B SE 437518B SE 7811382 A SE7811382 A SE 7811382A SE 7811382 A SE7811382 A SE 7811382A SE 437518 B SE437518 B SE 437518B
- Authority
- SE
- Sweden
- Prior art keywords
- compound
- benzodioxane
- formula
- chloroform
- solution
- Prior art date
Links
- -1 PIPERAZIN-1-YL Chemical class 0.000 title claims description 16
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 3
- 230000001105 regulatory effect Effects 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 13
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 206010020772 Hypertension Diseases 0.000 claims description 5
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 210000000748 cardiovascular system Anatomy 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 68
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 40
- 239000000243 solution Substances 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 239000000203 mixture Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 16
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 239000000284 extract Substances 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 239000012265 solid product Substances 0.000 description 6
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 230000036772 blood pressure Effects 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000002026 chloroform extract Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- HWIIAAVGRHKSOJ-UHFFFAOYSA-N 2-chloro-6,7-dimethoxyquinazolin-4-amine Chemical compound ClC1=NC(N)=C2C=C(OC)C(OC)=CC2=N1 HWIIAAVGRHKSOJ-UHFFFAOYSA-N 0.000 description 2
- VQBHRCHDEHKUIT-UHFFFAOYSA-N 2-methyl-3,4-dihydrochromene-2-carboxylic acid Chemical compound C1=CC=C2OC(C)(C(O)=O)CCC2=C1 VQBHRCHDEHKUIT-UHFFFAOYSA-N 0.000 description 2
- UCQUAMAQHHEXGD-UHFFFAOYSA-N 3',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C(O)=C1 UCQUAMAQHHEXGD-UHFFFAOYSA-N 0.000 description 2
- SFLFCQJQOIZMHF-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)CCC2=C1 SFLFCQJQOIZMHF-UHFFFAOYSA-N 0.000 description 2
- BMZPIKGWOWNDBR-UHFFFAOYSA-N 6,7-dimethoxy-2-(3-methylpiperazin-1-yl)quinazolin-4-amine Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N1CCNC(C)C1 BMZPIKGWOWNDBR-UHFFFAOYSA-N 0.000 description 2
- CNAIQDWMRUEWMJ-UHFFFAOYSA-N 6,7-dimethyl-2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound O1CC(C(O)=O)OC2=C1C=C(C)C(C)=C2 CNAIQDWMRUEWMJ-UHFFFAOYSA-N 0.000 description 2
- GCTSNZLKXRKWQQ-UHFFFAOYSA-N 6-acetyl-2,3-dihydro-1,4-benzodioxine-2-carboxylic acid Chemical compound O1C(C(O)=O)COC2=CC(C(=O)C)=CC=C21 GCTSNZLKXRKWQQ-UHFFFAOYSA-N 0.000 description 2
- ANUAEQPECBSTBE-UHFFFAOYSA-N 8-methoxy-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1CC(C(O)=O)OC2=C1C=CC=C2OC ANUAEQPECBSTBE-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 150000001649 bromium compounds Chemical class 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 2
- 235000019797 dipotassium phosphate Nutrition 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000001631 hypertensive effect Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- ROXQOUUAPQUMLN-UHFFFAOYSA-N methyl 2,3-dibromopropanoate Chemical compound COC(=O)C(Br)CBr ROXQOUUAPQUMLN-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000012286 potassium permanganate Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
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- IZDNTTWZMDCNJE-UHFFFAOYSA-N (2-methyl-3,4-dihydrochromen-2-yl)methanol Chemical compound C1=CC=C2OC(C)(CO)CCC2=C1 IZDNTTWZMDCNJE-UHFFFAOYSA-N 0.000 description 1
- LCPVSXSGRUODFB-UHFFFAOYSA-N (5-methyl-3,4-dihydro-2H-chromen-2-yl)methanol Chemical compound OCC1OC2=CC=CC(=C2CC1)C LCPVSXSGRUODFB-UHFFFAOYSA-N 0.000 description 1
- FTVQSTULKLORPY-UHFFFAOYSA-N (6-methoxy-2,3-dihydro-1,4-benzodioxin-2-yl)methanol Chemical compound O1C(CO)COC2=CC(OC)=CC=C21 FTVQSTULKLORPY-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- FLUPDJNTYCSBJZ-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-3-yl(piperazin-1-yl)methanone Chemical compound C1OC2=CC=CC=C2OC1C(=O)N1CCNCC1 FLUPDJNTYCSBJZ-UHFFFAOYSA-N 0.000 description 1
- JOMNTHCQHJPVAZ-UHFFFAOYSA-N 2-methylpiperazine Chemical compound CC1CNCCN1 JOMNTHCQHJPVAZ-UHFFFAOYSA-N 0.000 description 1
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- XLZHGKDRKSKCAU-UHFFFAOYSA-N 3-isopropylcatechol Chemical compound CC(C)C1=CC=CC(O)=C1O XLZHGKDRKSKCAU-UHFFFAOYSA-N 0.000 description 1
- VKQJFKLRXDLRNP-UHFFFAOYSA-N 4,5-dimethylbenzene-1,2-diol Chemical compound CC1=CC(O)=C(O)C=C1C VKQJFKLRXDLRNP-UHFFFAOYSA-N 0.000 description 1
- SVGANCYXHVJSRO-UHFFFAOYSA-N 5-methoxy-3,4-dihydro-2H-chromene-2-carboxamide Chemical compound O1C(C(N)=O)CCC2=C1C=CC=C2OC SVGANCYXHVJSRO-UHFFFAOYSA-N 0.000 description 1
- OXYPZDASCWCFGV-UHFFFAOYSA-N 5-methyl-3,4-dihydro-2H-chromene-2-carboxylic acid Chemical compound CC1=C2CCC(OC2=CC=C1)C(=O)O OXYPZDASCWCFGV-UHFFFAOYSA-N 0.000 description 1
- MZOAKOKTRSSQSO-UHFFFAOYSA-N 6,7-dichloro-2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound ClC1=C(Cl)C=C2OC(C(=O)O)COC2=C1 MZOAKOKTRSSQSO-UHFFFAOYSA-N 0.000 description 1
- FYMQPWWNOCENRN-UHFFFAOYSA-N 6,7-dimethoxyquinazoline Chemical compound N1=CN=C2C=C(OC)C(OC)=CC2=C1 FYMQPWWNOCENRN-UHFFFAOYSA-N 0.000 description 1
- DUHBKUNAJQULTQ-UHFFFAOYSA-N 6-acetyl-2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound O1CC(C(O)=O)OC2=CC(C(=O)C)=CC=C21 DUHBKUNAJQULTQ-UHFFFAOYSA-N 0.000 description 1
- UXXLBXQHCJQSRQ-UHFFFAOYSA-N 6-methoxy-2,3-dihydro-1,4-benzodioxine-2-carbonyl chloride Chemical compound O1C(C(Cl)=O)COC2=CC(OC)=CC=C21 UXXLBXQHCJQSRQ-UHFFFAOYSA-N 0.000 description 1
- YWNAHFMNEDUMSF-UHFFFAOYSA-N 6-methoxy-2,3-dihydro-1,4-benzodioxine-2-carboxylic acid Chemical compound O1C(C(O)=O)COC2=CC(OC)=CC=C21 YWNAHFMNEDUMSF-UHFFFAOYSA-N 0.000 description 1
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- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
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- 210000001367 artery Anatomy 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- DCPDRQNPPXSXIB-UHFFFAOYSA-N ethyl 2,2-dibromopropanoate Chemical compound CCOC(=O)C(C)(Br)Br DCPDRQNPPXSXIB-UHFFFAOYSA-N 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- MSQACBWWAIBWIC-UHFFFAOYSA-N hydron;piperazine;chloride Chemical compound Cl.C1CNCCN1 MSQACBWWAIBWIC-UHFFFAOYSA-N 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229920003217 poly(methylsilsesquioxane) Polymers 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 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
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Heart & Thoracic Surgery (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)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB4612877 | 1977-11-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE7811382L SE7811382L (sv) | 1979-05-06 |
| SE437518B true SE437518B (sv) | 1985-03-04 |
Family
ID=10439957
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE7811382A SE437518B (sv) | 1977-11-05 | 1978-11-02 | Nya derivat av 4-amino-2-(piperazin-1-yl eller homopiperazin-1-yl)kinazolin, sett att framstella denna och farmaceutisk beredning for reglering av det kardiovaskulera systemet |
Country Status (36)
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1985002617A1 (en) * | 1983-12-14 | 1985-06-20 | Takeda Chemical Industries. Ltd. | 1,5-benzoxathiepin derivatives and process for their preparation |
| WO1985004658A1 (en) * | 1984-04-04 | 1985-10-24 | Takeda Chemical Industries, Ltd. | 1,5-benzoxathiepine derivatives and their preparation |
| WO1986002644A1 (en) * | 1984-11-01 | 1986-05-09 | Takeda Chemical Industries, Ltd. | 1,5-benzoxathiepin derivatives and process for their preparation |
| DE59611417D1 (de) * | 1996-12-20 | 2007-03-29 | Heumann Pharma Gmbh & Co | Neue polymorphe Form von Doxazosinmesylat (Form III) |
| EP0849265A1 (de) * | 1996-12-20 | 1998-06-24 | HEUMANN PHARMA GmbH | Neue polymorphe Form von Doxazosin-Mesylat (Form II) |
| EP0849264A1 (de) * | 1996-12-20 | 1998-06-24 | HEUMANN PHARMA GmbH | Neue polymorphe Form von doxazosinmesylat (Form I) |
| TW448155B (en) * | 1999-03-29 | 2001-08-01 | Dev Center Biotechnology | Method for producing amide compounds and quinazolin derivatives |
| EP1403263B1 (en) * | 2002-09-27 | 2005-06-22 | Council of Scientific and Industrial Research | Process for the preparation of N-(2,3-dihydrobenzo 1,4 dioxin-2-carbonyl) piperazine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3663706A (en) * | 1969-09-29 | 1972-05-16 | Pfizer | Use of 2,4-diaminoquinazolines as hypotensive agents |
| US3669968A (en) * | 1970-05-21 | 1972-06-13 | Pfizer | Trialkoxy quinazolines |
-
1978
- 1978-09-27 DK DK428678A patent/DK154082C/da active
- 1978-10-03 IN IN712/DEL/78A patent/IN148828B/en unknown
- 1978-10-24 PH PH21726A patent/PH13966A/en unknown
- 1978-10-24 CA CA314,027A patent/CA1088059A/en not_active Expired
- 1978-10-31 UA UA2679598A patent/UA8324A1/uk unknown
- 1978-10-31 SU SU782679598A patent/SU816403A3/ru active
- 1978-11-02 CS CS787166A patent/CS207671B2/cs unknown
- 1978-11-02 HU HU78PI648A patent/HU176306B/hu unknown
- 1978-11-02 JP JP13569578A patent/JPS5498792A/ja active Granted
- 1978-11-02 FI FI783347A patent/FI64366C/fi not_active IP Right Cessation
- 1978-11-02 IL IL55857A patent/IL55857A/xx unknown
- 1978-11-02 DE DE2847623A patent/DE2847623C2/de not_active Expired
- 1978-11-02 AR AR274321A patent/AR219562A1/es active
- 1978-11-02 PT PT68735A patent/PT68735A/pt unknown
- 1978-11-02 GR GR57562A patent/GR81514B/el unknown
- 1978-11-02 SE SE7811382A patent/SE437518B/sv not_active IP Right Cessation
- 1978-11-02 YU YU2553/78A patent/YU40204B/xx unknown
- 1978-11-02 AT AT0784378A patent/AT365186B/de not_active IP Right Cessation
- 1978-11-02 NL NLAANVRAGE7810909,A patent/NL174549C/xx not_active IP Right Cessation
- 1978-11-02 ZA ZA00786184A patent/ZA786184B/xx unknown
- 1978-11-02 CH CH1132178A patent/CH643255A5/de not_active IP Right Cessation
- 1978-11-02 NZ NZ188813A patent/NZ188813A/xx unknown
- 1978-11-03 PL PL1978216980A patent/PL119419B1/pl unknown
- 1978-11-03 LU LU80470A patent/LU80470A1/fr unknown
- 1978-11-03 ES ES474805A patent/ES474805A1/es not_active Expired
- 1978-11-03 NO NO783705A patent/NO150158C/no unknown
- 1978-11-03 IT IT29434/78A patent/IT1100919B/it active Protection Beyond IP Right Term
- 1978-11-03 AU AU41322/78A patent/AU509329B2/en not_active Expired
- 1978-11-03 PL PL1978210681A patent/PL119586B1/pl unknown
- 1978-11-03 FR FR7831126A patent/FR2407929A1/fr active Granted
- 1978-11-03 DD DD78208868A patent/DD139850A5/de unknown
- 1978-11-03 IE IE2179/78A patent/IE47888B1/en active Protection Beyond IP Right Term
- 1978-11-03 BE BE191544A patent/BE871771A/xx not_active IP Right Cessation
- 1978-11-04 EG EG641/78A patent/EG13594A/xx active
-
1979
- 1979-04-30 ES ES480121A patent/ES480121A0/es active Granted
- 1979-10-18 AR AR278545A patent/AR223015A1/es active
-
1983
- 1983-02-17 YU YU386/83A patent/YU40419B/xx unknown
- 1983-11-21 KE KE3350A patent/KE3350A/xx unknown
-
1984
- 1984-11-29 HK HK942/84A patent/HK94284A/xx not_active IP Right Cessation
-
1985
- 1985-12-30 MY MY286/85A patent/MY8500286A/xx unknown
-
1991
- 1991-11-22 CS CS913544A patent/CS354491A3/cs unknown
-
1993
- 1993-06-11 NL NL930062C patent/NL930062I2/nl unknown
- 1993-06-24 LU LU88331C patent/LU88331I2/fr unknown
Also Published As
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