CZ106996A3 - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- CZ106996A3 CZ106996A3 CZ961069A CZ106996A CZ106996A3 CZ 106996 A3 CZ106996 A3 CZ 106996A3 CZ 961069 A CZ961069 A CZ 961069A CZ 106996 A CZ106996 A CZ 106996A CZ 106996 A3 CZ106996 A3 CZ 106996A3
- Authority
- CZ
- Czechia
- Prior art keywords
- triazolo
- pyrimidine
- ethyl
- formula
- compounds
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 264
- -1 cyano, hydroxy Chemical group 0.000 claims abstract description 71
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 33
- 206010010904 Convulsion Diseases 0.000 claims abstract description 29
- 125000005843 halogen group Chemical group 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 23
- 230000006378 damage Effects 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 11
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 11
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 11
- 208000032843 Hemorrhage Diseases 0.000 claims abstract description 10
- 206010015037 epilepsy Diseases 0.000 claims abstract description 10
- 238000011282 treatment Methods 0.000 claims abstract description 10
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 9
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 9
- 230000000926 neurological effect Effects 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 206010019196 Head injury Diseases 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 13
- 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 12
- 241001465754 Metazoa Species 0.000 claims description 11
- 125000001589 carboacyl group Chemical group 0.000 claims description 11
- 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 9
- 208000029028 brain injury Diseases 0.000 claims description 8
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 7
- 241000282414 Homo sapiens Species 0.000 claims description 7
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 5
- DAMUBRAZMMOTHY-UHFFFAOYSA-N 7-[1-(4-methylsulfanylphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C1=CC(SC)=CC=C1OC(C)C1=CC=NC2=NC=NN12 DAMUBRAZMMOTHY-UHFFFAOYSA-N 0.000 claims description 5
- QOAYBGGYBZKPPA-UHFFFAOYSA-N 7-[1-(4-methylsulfonylphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(S(C)(=O)=O)C=C1 QOAYBGGYBZKPPA-UHFFFAOYSA-N 0.000 claims description 5
- 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 description 4
- KNFQKACFWUSMOB-UHFFFAOYSA-N 7-[1-(2-chloro-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=C1Cl KNFQKACFWUSMOB-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 4
- 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 description 4
- 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 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
- 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 3
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 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 3
- ZRVJOPMTANXDOX-UHFFFAOYSA-N 7-[1-(3-chlorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=CC(Cl)=C1 ZRVJOPMTANXDOX-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- JCGNIAAPBYXVEH-UHFFFAOYSA-N 7-[1-(4-ethylsulfanylphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C1=CC(SCC)=CC=C1OC(C)C1=CC=NC2=NC=NN12 JCGNIAAPBYXVEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 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 description 2
- SCLBUULVTPJYGC-UHFFFAOYSA-N 7-[2-(4-chlorophenoxy)propan-2-yl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)(C)OC1=CC=C(Cl)C=C1 SCLBUULVTPJYGC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 2
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 2
- XOCCGFZIVGVNDL-UHFFFAOYSA-N 7-[1-(4-methylsulfinylphenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=C(S(C)=O)C=C1 XOCCGFZIVGVNDL-UHFFFAOYSA-N 0.000 claims 2
- 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
- VFMPGXYNNSGZBT-UHFFFAOYSA-N 7-[1-(4-chlorophenoxy)propyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(CC)OC1=CC=C(Cl)C=C1 VFMPGXYNNSGZBT-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 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 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 4
- 208000006011 Stroke Diseases 0.000 abstract description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 142
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
- 239000000243 solution Substances 0.000 description 67
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 64
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- 238000003556 assay Methods 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 230000002829 reductive effect Effects 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
- 235000019341 magnesium sulphate Nutrition 0.000 description 22
- 238000001953 recrystallisation Methods 0.000 description 20
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 18
- 235000002639 sodium chloride Nutrition 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- 238000001914 filtration Methods 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 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 14
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 239000012043 crude product Substances 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
- 150000002431 hydrogen Chemical class 0.000 description 11
- 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 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 150000001298 alcohols Chemical class 0.000 description 9
- 230000008020 evaporation Effects 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000839 emulsion 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
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 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 7
- 239000002775 capsule Substances 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000001923 methylcellulose Substances 0.000 description 7
- 235000010981 methylcellulose Nutrition 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 7
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000003995 emulsifying agent Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 6
- 229910052737 gold Inorganic materials 0.000 description 6
- 239000010931 gold Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 229920000609 methyl cellulose Polymers 0.000 description 6
- 239000006186 oral dosage form Substances 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 230000000699 topical effect Effects 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 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 5
- 230000001773 anti-convulsant effect Effects 0.000 description 5
- 239000001961 anticonvulsive agent Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 5
- 230000000694 effects Effects 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
- 239000008187 granular material Substances 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 239000003377 acid catalyst Substances 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 229960003965 antiepileptics Drugs 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 229950005499 carbon tetrachloride Drugs 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000004811 liquid chromatography Methods 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000000463 material Substances 0.000 description 4
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- 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
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (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 (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939321162A GB9321162D0 (en) | 1993-10-13 | 1993-10-13 | Therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ106996A3 true CZ106996A3 (en) | 1996-09-11 |
Family
ID=10743505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ961069A CZ106996A3 (en) | 1993-10-13 | 1994-10-12 | Pharmaceutical composition |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US5753665A (OSRAM) |
| EP (1) | EP0723546B1 (OSRAM) |
| JP (1) | JPH09503771A (OSRAM) |
| CN (1) | CN1040537C (OSRAM) |
| AT (1) | ATE188966T1 (OSRAM) |
| AU (1) | AU679573B2 (OSRAM) |
| BG (1) | BG62405B1 (OSRAM) |
| BR (1) | BR9407812A (OSRAM) |
| CA (1) | CA2173857A1 (OSRAM) |
| CZ (1) | CZ106996A3 (OSRAM) |
| DE (1) | DE69422724T2 (OSRAM) |
| DK (1) | DK0723546T3 (OSRAM) |
| ES (1) | ES2142413T3 (OSRAM) |
| FI (1) | FI961630A0 (OSRAM) |
| GB (1) | GB9321162D0 (OSRAM) |
| GR (1) | GR3032480T3 (OSRAM) |
| HU (1) | HUT74580A (OSRAM) |
| IL (1) | IL111259A (OSRAM) |
| IN (1) | IN179169B (OSRAM) |
| MY (1) | MY112110A (OSRAM) |
| NO (1) | NO306509B1 (OSRAM) |
| NZ (1) | NZ274500A (OSRAM) |
| PL (1) | PL177920B1 (OSRAM) |
| PT (1) | PT723546E (OSRAM) |
| RO (1) | RO117020B1 (OSRAM) |
| RU (1) | RU2136684C1 (OSRAM) |
| SK (1) | SK282329B6 (OSRAM) |
| TW (1) | TW372237B (OSRAM) |
| UA (1) | UA42738C2 (OSRAM) |
| WO (1) | WO1995010521A1 (OSRAM) |
| ZA (1) | ZA947949B (OSRAM) |
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 |
| AU723098B2 (en) * | 1996-07-25 | 2000-08-17 | Merck Sharp & Dohme Limited | Substituted triazolo-pyridazine derivatives as ligands for GABA receptors |
| GB9617727D0 (en) | 1996-08-23 | 1996-10-02 | Knoll Ag | Process |
| GB9626746D0 (en) * | 1996-12-23 | 1997-02-12 | Knoll Ag | Process |
| DE19706337A1 (de) * | 1997-02-19 | 1998-08-20 | Basf Ag | Verfahren zur Herstellung von enantiomerenreinen Estern |
| DE19706336A1 (de) * | 1997-02-19 | 1998-08-20 | Basf Ag | Verfahren zur Herstellung von enantiomerenreinen Alkoholen |
| DE19707008A1 (de) * | 1997-02-21 | 1998-08-27 | Basf Ag | Verfahren zur Herstellung von enantiomerenreinen Alkoholen |
| AU760688B2 (en) | 1998-10-16 | 2003-05-22 | Merck Sharp & Dohme Limited | Pyrazolo-triazine derivatives as ligands for GABA receptors |
| 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 |
| GB9906124D0 (en) * | 1999-03-18 | 1999-05-12 | Knoll Ag | Therapeutic agent |
| GB9914743D0 (en) * | 1999-06-24 | 1999-08-25 | Knoll Ag | Therapeutic agents |
| JP2004502691A (ja) * | 2000-06-30 | 2004-01-29 | ワイス | 抗癌薬としての置換トリアゾロピリミジン |
| 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 |
| CA2554696C (en) | 2004-02-13 | 2009-06-30 | Warner-Lambert Company Llc | Androgen receptor modulators |
| EP1737813A1 (en) | 2004-04-13 | 2007-01-03 | Warner-Lambert Company LLC | Androgen modulators |
| WO2005102990A1 (en) | 2004-04-22 | 2005-11-03 | Warner-Lambert Company Llc | Androgen modulators |
| TW200724139A (en) | 2005-05-05 | 2007-07-01 | Warner Lambert Co | Androgen modulators |
| ES2451542T3 (es) * | 2008-08-29 | 2014-03-27 | Concert Pharmaceuticals Inc. | Derivados de triazolo-piridazina sustituidos |
| DK2414365T3 (da) * | 2009-04-01 | 2014-03-31 | Aniona Aps | SUBSTITUEREDE [1,2,4]TRIAZOLO[1,5-a]PYRIMIDINER OG ANVENDELSE HERAF SOM KALIUMKANALMODULATORER |
| US20120095025A1 (en) * | 2009-04-01 | 2012-04-19 | Neurosearch A/S | SUBSTITUTED [1,2,4]TRIAZOLO[1,5-a]PYRIMIDINES AND THEIR USE AS POTASSIUM CHANNEL MODULATORS |
| 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 |
| WO2020231723A1 (en) | 2019-05-13 | 2020-11-19 | 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 DK DK94929537T patent/DK0723546T3/da active
- 1994-10-12 AU AU78554/94A patent/AU679573B2/en not_active Ceased
- 1994-10-12 BR BR9407812A patent/BR9407812A/pt not_active Application Discontinuation
- 1994-10-12 RU RU96108927A patent/RU2136684C1/ru active
- 1994-10-12 HU HU9600959A patent/HUT74580A/hu unknown
- 1994-10-12 ES ES94929537T patent/ES2142413T3/es not_active Expired - Lifetime
- 1994-10-12 CA CA002173857A patent/CA2173857A1/en not_active Abandoned
- 1994-10-12 JP JP7511287A patent/JPH09503771A/ja not_active Ceased
- 1994-10-12 SK SK437-96A patent/SK282329B6/sk unknown
- 1994-10-12 US US08/628,662 patent/US5753665A/en not_active Expired - Lifetime
- 1994-10-12 EP EP94929537A patent/EP0723546B1/en not_active Expired - Lifetime
- 1994-10-12 CZ CZ961069A patent/CZ106996A3/cs unknown
- 1994-10-12 PT PT94929537T patent/PT723546E/pt unknown
- 1994-10-12 PL PL94313970A patent/PL177920B1/pl unknown
- 1994-10-12 DE DE69422724T patent/DE69422724T2/de not_active Expired - Lifetime
- 1994-10-12 RO RO96-00795A patent/RO117020B1/ro unknown
- 1994-10-12 IL IL111259A patent/IL111259A/en not_active IP Right Cessation
- 1994-10-12 CN CN94194265A patent/CN1040537C/zh not_active Expired - Fee Related
- 1994-10-12 AT AT94929537T patent/ATE188966T1/de not_active IP Right Cessation
- 1994-10-12 WO PCT/EP1994/003364 patent/WO1995010521A1/en not_active Ceased
- 1994-10-12 NZ NZ274500A patent/NZ274500A/en unknown
- 1994-10-12 UA UA96041428A patent/UA42738C2/uk unknown
- 1994-10-12 ZA ZA947949A patent/ZA947949B/xx unknown
- 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/FI961630A0/fi unknown
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2000
- 2000-01-26 GR GR20000400175T patent/GR3032480T3/el not_active IP Right Cessation
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| PD00 | Pending as of 2000-06-30 in czech republic |