RO117020B1 - DERIVATI DE 1,2,4-TRIAZOL [1,5-a]PIRIMIDINA SI PROCEDEU DE OBTINERE A ACESTORA - Google Patents
DERIVATI DE 1,2,4-TRIAZOL [1,5-a]PIRIMIDINA SI PROCEDEU DE OBTINERE A ACESTORA Download PDFInfo
- Publication number
- RO117020B1 RO117020B1 RO96-00795A RO9600795A RO117020B1 RO 117020 B1 RO117020 B1 RO 117020B1 RO 9600795 A RO9600795 A RO 9600795A RO 117020 B1 RO117020 B1 RO 117020B1
- Authority
- RO
- Romania
- Prior art keywords
- pyrimidine
- triazolo
- ethyl
- formula
- compounds
- Prior art date
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- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 150000003230 pyrimidines Chemical class 0.000 title claims abstract description 17
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title claims abstract description 16
- 238000004519 manufacturing process Methods 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 254
- 239000002904 solvent Substances 0.000 claims abstract description 64
- 238000006243 chemical reaction Methods 0.000 claims abstract description 36
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 19
- 238000011282 treatment Methods 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims description 151
- -1 cyano, hydroxy Chemical group 0.000 claims description 78
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000005843 halogen group Chemical group 0.000 claims description 26
- 206010010904 Convulsion Diseases 0.000 claims description 24
- 238000000034 method Methods 0.000 claims description 22
- 208000025966 Neurological disease Diseases 0.000 claims description 17
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 12
- 241001465754 Metazoa Species 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 150000001298 alcohols Chemical class 0.000 claims description 10
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 239000000543 intermediate Substances 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 230000001225 therapeutic effect Effects 0.000 claims description 9
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- 206010015037 epilepsy Diseases 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 8
- 208000032843 Hemorrhage Diseases 0.000 claims description 7
- FCEPUTGEUCVRRI-UHFFFAOYSA-N 7-[1-(4-chlorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(Cl)C=C1 FCEPUTGEUCVRRI-UHFFFAOYSA-N 0.000 claims description 6
- 239000003377 acid catalyst Substances 0.000 claims description 6
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 150000001450 anions Chemical class 0.000 claims description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 239000007822 coupling agent Substances 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 3
- VUJAOETYODJPOS-UHFFFAOYSA-N 7-[1-(4-fluorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(F)C=C1 VUJAOETYODJPOS-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 150000002989 phenols Chemical class 0.000 claims description 3
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 2
- UAKRICMNLSRISL-UHFFFAOYSA-N 1-[4-[1-([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)ethoxy]phenyl]ethanone Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(C(C)=O)C=C1 UAKRICMNLSRISL-UHFFFAOYSA-N 0.000 claims description 2
- CWJSGPLPYFBOGX-UHFFFAOYSA-N 7-[1-(2,4-dichlorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(Cl)C=C1Cl CWJSGPLPYFBOGX-UHFFFAOYSA-N 0.000 claims description 2
- KZXQJKAJKRZZDK-UHFFFAOYSA-N 7-[1-(2,4-difluorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(F)C=C1F KZXQJKAJKRZZDK-UHFFFAOYSA-N 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001153 fluoro group Chemical group F* 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 1
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
- BEWOAZYLVJYVMO-UHFFFAOYSA-N 4-[1-([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)ethoxy]benzonitrile Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(C#N)C=C1 BEWOAZYLVJYVMO-UHFFFAOYSA-N 0.000 claims 1
- AONXGEYUTVOOOO-UHFFFAOYSA-N 7-[(4-chlorophenoxy)methyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C1=CC(Cl)=CC=C1OCC1=CC=NC2=NC=NN12 AONXGEYUTVOOOO-UHFFFAOYSA-N 0.000 claims 1
- HDLHXYFXJHGDOR-UHFFFAOYSA-N 7-[1-(3,4-dichlorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(Cl)C(Cl)=C1 HDLHXYFXJHGDOR-UHFFFAOYSA-N 0.000 claims 1
- DDCKRPUTULJVPC-UHFFFAOYSA-N 7-[1-(4-bromophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(Br)C=C1 DDCKRPUTULJVPC-UHFFFAOYSA-N 0.000 claims 1
- KFSMQDIGWKNFBO-UHFFFAOYSA-N 7-[1-(4-chlorophenoxy)ethyl]-2-methyl-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC(C)=NN2C=1C(C)OC1=CC=C(Cl)C=C1 KFSMQDIGWKNFBO-UHFFFAOYSA-N 0.000 claims 1
- ZGJNYZAHWGQJCU-UHFFFAOYSA-N 7-[1-(4-methoxyphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C1=CC(OC)=CC=C1OC(C)C1=CC=NC2=NC=NN12 ZGJNYZAHWGQJCU-UHFFFAOYSA-N 0.000 claims 1
- XAJABHCRHXABGJ-UHFFFAOYSA-N 7-[1-[4-(trifluoromethoxy)phenoxy]ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(OC(F)(F)F)C=C1 XAJABHCRHXABGJ-UHFFFAOYSA-N 0.000 claims 1
- AOPCMPFQNOFJOG-UHFFFAOYSA-N 7-[1-[4-(trifluoromethyl)phenoxy]ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(C(F)(F)F)C=C1 AOPCMPFQNOFJOG-UHFFFAOYSA-N 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 230000003902 lesion Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 91
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 66
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 63
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
- 238000012360 testing method Methods 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 38
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- 238000003756 stirring Methods 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
- 235000019341 magnesium sulphate Nutrition 0.000 description 25
- 241000699670 Mus sp. Species 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 238000001914 filtration Methods 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 18
- 235000017557 sodium bicarbonate Nutrition 0.000 description 18
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 18
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 18
- 235000019441 ethanol Nutrition 0.000 description 17
- 238000001704 evaporation Methods 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- 230000008020 evaporation Effects 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- 239000008194 pharmaceutical composition Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- 238000003556 assay Methods 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 238000001953 recrystallisation Methods 0.000 description 9
- RVHATPHZTRBGPP-UHFFFAOYSA-N 7-(1-bromoethyl)-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound CC(Br)C1=CC=NC2=NC=NN12 RVHATPHZTRBGPP-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 208000006011 Stroke Diseases 0.000 description 8
- 239000001961 anticonvulsive agent Substances 0.000 description 8
- 239000000839 emulsion Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 150000001721 carbon Chemical group 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000006186 oral dosage form Substances 0.000 description 7
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 6
- KJPYETXOQANQSE-UHFFFAOYSA-N 1-([1,2,4]triazolo[1,5-a]pyrimidin-7-yl)ethanol Chemical compound CC(O)C1=CC=NC2=NC=NN12 KJPYETXOQANQSE-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- 241000282412 Homo Species 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- 230000001773 anti-convulsant effect Effects 0.000 description 6
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- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 229920000609 methyl cellulose Polymers 0.000 description 6
- 239000001923 methylcellulose Substances 0.000 description 6
- 235000010981 methylcellulose Nutrition 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 5
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 5
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 5
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 5
- 229910052737 gold Inorganic materials 0.000 description 5
- 239000010931 gold Substances 0.000 description 5
- 239000008187 granular material Substances 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical group 0.000 description 5
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- 125000001424 substituent group Chemical group 0.000 description 5
- IWYDHOAUDWTVEP-SSDOTTSWSA-M (R)-mandelate Chemical compound [O-]C(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-M 0.000 description 4
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
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- 206010019196 Head injury Diseases 0.000 description 4
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
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- 208000029028 brain injury Diseases 0.000 description 4
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- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 125000006083 1-bromoethyl group Chemical group 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
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- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 125000005236 alkanoylamino group Chemical group 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000002585 base Substances 0.000 description 3
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- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000001640 fractional crystallisation Methods 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
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- 239000005457 ice water Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
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- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939321162A GB9321162D0 (en) | 1993-10-13 | 1993-10-13 | Therapeutic agents |
| PCT/EP1994/003364 WO1995010521A1 (en) | 1993-10-13 | 1994-10-12 | Therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RO117020B1 true RO117020B1 (ro) | 2001-09-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RO96-00795A RO117020B1 (ro) | 1993-10-13 | 1994-10-12 | DERIVATI DE 1,2,4-TRIAZOL [1,5-a]PIRIMIDINA SI PROCEDEU DE OBTINERE A ACESTORA |
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| IN (1) | IN179169B (forum.php) |
| MY (1) | MY112110A (forum.php) |
| NO (1) | NO306509B1 (forum.php) |
| NZ (1) | NZ274500A (forum.php) |
| PL (1) | PL177920B1 (forum.php) |
| PT (1) | PT723546E (forum.php) |
| RO (1) | RO117020B1 (forum.php) |
| RU (1) | RU2136684C1 (forum.php) |
| SK (1) | SK282329B6 (forum.php) |
| TW (1) | TW372237B (forum.php) |
| UA (1) | UA42738C2 (forum.php) |
| WO (1) | WO1995010521A1 (forum.php) |
| ZA (1) | ZA947949B (forum.php) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9506382D0 (en) * | 1995-03-29 | 1995-05-17 | Boots Co Plc | Pharmaceutical compositions |
| GB9507348D0 (en) * | 1995-04-08 | 1995-05-31 | Knoll Ag | Therapeutic agents |
| US5714607A (en) * | 1995-12-01 | 1998-02-03 | American Cyanamid Company | Process improvement in the synthesis of N- 3-(3-cyano-pyrazolo 1,5-a!pyrimidin-7-yl)phenyl!-N-ethylacetamide |
| KR20000029548A (ko) | 1996-07-25 | 2000-05-25 | 더블유. 지. 콜 | 가바수용체에대한리간드로서의치환된트리아졸로-피리다진유도체 |
| GB9617727D0 (en) * | 1996-08-23 | 1996-10-02 | Knoll Ag | Process |
| GB9626746D0 (en) * | 1996-12-23 | 1997-02-12 | Knoll Ag | Process |
| DE19706336A1 (de) * | 1997-02-19 | 1998-08-20 | Basf Ag | Verfahren zur Herstellung von enantiomerenreinen Alkoholen |
| DE19706337A1 (de) * | 1997-02-19 | 1998-08-20 | Basf Ag | Verfahren zur Herstellung von enantiomerenreinen Estern |
| DE19707008A1 (de) * | 1997-02-21 | 1998-08-27 | Basf Ag | Verfahren zur Herstellung von enantiomerenreinen Alkoholen |
| WO2000023449A1 (en) * | 1998-10-16 | 2000-04-27 | Merck Sharp & Dohme Limited | Pyrazolo-triazine derivatives as ligands for gaba receptors |
| GB9906124D0 (en) * | 1999-03-18 | 1999-05-12 | Knoll Ag | Therapeutic agent |
| GB9906130D0 (en) * | 1999-03-18 | 1999-05-12 | Knoll Ag | Compounds for use in therapy |
| GB9906126D0 (en) * | 1999-03-18 | 1999-05-12 | Knoll Ag | Pharmaceutical formulations |
| GB9914743D0 (en) * | 1999-06-24 | 1999-08-25 | Knoll Ag | Therapeutic agents |
| GEP20053688B (en) * | 2000-06-30 | 2005-12-12 | Wyeth Corp | Substituted-Triazolopyrimidines as Anticancer Agents |
| TWI334868B (en) * | 2003-06-03 | 2010-12-21 | Nippon Kayaku Kk | [1,2,4] triazoro [1,5-a] pyrimidine-2-ylurea derivative and use thereof |
| BRPI0507670A (pt) | 2004-02-13 | 2007-07-17 | Warner Lambert Co | moduladores do receptor de androgênio |
| WO2005100305A1 (en) | 2004-04-13 | 2005-10-27 | Warner-Lambert Company Llc | Androgen modulators |
| EP1740533A1 (en) | 2004-04-22 | 2007-01-10 | Warner-Lambert Company LLC | Androgen modulators |
| TW200724139A (en) | 2005-05-05 | 2007-07-01 | Warner Lambert Co | Androgen modulators |
| AU2009285533B2 (en) * | 2008-08-29 | 2014-02-13 | Concert Pharmaceuticals Inc. | Substituted triazolo-pyridazine derivatives |
| US8685987B2 (en) | 2009-04-01 | 2014-04-01 | Ataxion, Inc. | Substituted [1,2,4]triazolo[1,5-a]pyrimidines and their use as potassium channel modulators |
| WO2010112484A1 (en) * | 2009-04-01 | 2010-10-07 | Neurosearch A/S | SUBSTITUTED [1,2,4]TRIAZOLO[1,5-a]PYRIMIDINES AND THEIR USE AS POTASSIUM CHANNEL MODULATORS |
| DK2414365T3 (da) * | 2009-04-01 | 2014-03-31 | Aniona Aps | SUBSTITUEREDE [1,2,4]TRIAZOLO[1,5-a]PYRIMIDINER OG ANVENDELSE HERAF SOM KALIUMKANALMODULATORER |
| US11814734B2 (en) | 2019-05-13 | 2023-11-14 | Ecolab Usa Inc. | 1,2,4-triazolo[1,5-a] pyrimidine derivative as copper corrosion inhibitor |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE46306B1 (en) * | 1977-02-11 | 1983-05-04 | Ici Ltd | Safeguarded toxic chemical compositions containing an emetic |
| FR2549834B1 (fr) * | 1983-07-25 | 1985-10-18 | Sanofi Sa | Derives de triazolo-pyrimidine, leur procede de preparation et leur application therapeutique en tant que tonicardiaques |
| WO1989001478A1 (en) * | 1987-08-07 | 1989-02-23 | The Australian National University | ARYLOXY- AND ARALKYLTHIO-IMIDAZO[1,2-b]PYRIDAZINES |
| US5387747A (en) * | 1992-02-24 | 1995-02-07 | Laboratoires Upsa | Triazolopyrimidine derivatives which are angiotensin II receptor antagonists, their methods of preparation and pharmaceutical compositions in which they are present |
-
1993
- 1993-10-13 GB GB939321162A patent/GB9321162D0/en active Pending
-
1994
- 1994-10-11 IN IN982MA1994 patent/IN179169B/en unknown
- 1994-10-12 JP JP7511287A patent/JPH09503771A/ja not_active Ceased
- 1994-10-12 WO PCT/EP1994/003364 patent/WO1995010521A1/en not_active Application Discontinuation
- 1994-10-12 US US08/628,662 patent/US5753665A/en not_active Expired - Lifetime
- 1994-10-12 CA CA002173857A patent/CA2173857A1/en not_active Abandoned
- 1994-10-12 ZA ZA947949A patent/ZA947949B/xx unknown
- 1994-10-12 EP EP94929537A patent/EP0723546B1/en not_active Expired - Lifetime
- 1994-10-12 RO RO96-00795A patent/RO117020B1/ro unknown
- 1994-10-12 AU AU78554/94A patent/AU679573B2/en not_active Ceased
- 1994-10-12 HU HU9600959A patent/HUT74580A/hu unknown
- 1994-10-12 ES ES94929537T patent/ES2142413T3/es not_active Expired - Lifetime
- 1994-10-12 PT PT94929537T patent/PT723546E/pt unknown
- 1994-10-12 DK DK94929537T patent/DK0723546T3/da active
- 1994-10-12 CZ CZ961069A patent/CZ106996A3/cs unknown
- 1994-10-12 CN CN94194265A patent/CN1040537C/zh not_active Expired - Fee Related
- 1994-10-12 PL PL94313970A patent/PL177920B1/pl unknown
- 1994-10-12 SK SK437-96A patent/SK282329B6/sk unknown
- 1994-10-12 NZ NZ274500A patent/NZ274500A/en unknown
- 1994-10-12 RU RU96108927A patent/RU2136684C1/ru active
- 1994-10-12 AT AT94929537T patent/ATE188966T1/de not_active IP Right Cessation
- 1994-10-12 UA UA96041428A patent/UA42738C2/uk unknown
- 1994-10-12 IL IL111259A patent/IL111259A/en not_active IP Right Cessation
- 1994-10-12 BR BR9407812A patent/BR9407812A/pt not_active Application Discontinuation
- 1994-10-12 DE DE69422724T patent/DE69422724T2/de not_active Expired - Lifetime
- 1994-10-13 MY MYPI94002724A patent/MY112110A/en unknown
-
1995
- 1995-04-12 TW TW084103591A patent/TW372237B/zh active
-
1996
- 1996-04-09 BG BG100485A patent/BG62405B1/bg unknown
- 1996-04-11 NO NO961435A patent/NO306509B1/no not_active IP Right Cessation
- 1996-04-12 FI FI961630A patent/FI961630A7/fi unknown
-
2000
- 2000-01-26 GR GR20000400175T patent/GR3032480T3/el not_active IP Right Cessation
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