PT723546E - Blocos primitivos de 1,2,4-triazolo(1,5-a) e a sua utilizacao no tratamento de desordens neurologicas - Google Patents
Blocos primitivos de 1,2,4-triazolo(1,5-a) e a sua utilizacao no tratamento de desordens neurologicas Download PDFInfo
- Publication number
- PT723546E PT723546E PT94929537T PT94929537T PT723546E PT 723546 E PT723546 E PT 723546E PT 94929537 T PT94929537 T PT 94929537T PT 94929537 T PT94929537 T PT 94929537T PT 723546 E PT723546 E PT 723546E
- Authority
- PT
- Portugal
- Prior art keywords
- triazolo
- pyrimidine
- ethyl
- formula
- compounds
- Prior art date
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 15
- 208000012902 Nervous system disease Diseases 0.000 title claims abstract description 14
- 208000025966 Neurological disease Diseases 0.000 title claims abstract description 12
- -1 cyano, hydroxy Chemical group 0.000 claims abstract description 48
- 206010010904 Convulsion Diseases 0.000 claims abstract description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 14
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 13
- 230000006378 damage Effects 0.000 claims abstract description 13
- 206010015037 epilepsy Diseases 0.000 claims abstract description 12
- 230000000926 neurological effect Effects 0.000 claims abstract description 12
- 238000011321 prophylaxis Methods 0.000 claims abstract description 10
- 206010019196 Head injury Diseases 0.000 claims abstract description 9
- 208000032843 Hemorrhage Diseases 0.000 claims abstract description 9
- 208000030886 Traumatic Brain injury Diseases 0.000 claims abstract description 7
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 6
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 7
- 150000001875 compounds Chemical class 0.000 claims description 272
- 239000000203 mixture Substances 0.000 claims description 157
- 229910052736 halogen Inorganic materials 0.000 claims description 31
- 150000002367 halogens Chemical group 0.000 claims description 31
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 15
- 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 13
- 241001465754 Metazoa Species 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 208000010125 myocardial infarction Diseases 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 150000001298 alcohols Chemical class 0.000 claims description 9
- 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 8
- 230000000740 bleeding effect Effects 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 6
- XJQALWLMESTHMC-UHFFFAOYSA-N 7-[1-(2-fluorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound C=1C=NC2=NC=NN2C=1C(C)OC1=CC=CC=C1F XJQALWLMESTHMC-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 208000034158 bleeding Diseases 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 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
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
- 239000003377 acid catalyst Substances 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 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
- 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 4
- 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 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
- 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 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
- 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 4
- 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 description 4
- 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 description 4
- 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 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 4
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 3
- 125000004845 (C1-C6) alkylsulfonylamino 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
- 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 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
- 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 3
- 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 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 208000029028 brain injury Diseases 0.000 claims description 3
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical group OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 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 2
- 239000007822 coupling agent Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 4
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 2
- 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 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 125000005236 alkanoylamino group Chemical group 0.000 claims 1
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
- 230000008878 coupling Effects 0.000 claims 1
- 238000010168 coupling process Methods 0.000 claims 1
- 238000005859 coupling reaction Methods 0.000 claims 1
- 150000002989 phenols Chemical class 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 3
- 125000005843 halogen group Chemical group 0.000 abstract 5
- 208000006011 Stroke Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 90
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 73
- 239000000243 solution Substances 0.000 description 69
- 239000002904 solvent Substances 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
- 238000012360 testing method Methods 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 47
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- 235000002639 sodium chloride Nutrition 0.000 description 21
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- 241000700159 Rattus Species 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- 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
- 239000003480 eluent Substances 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- 238000001953 recrystallisation Methods 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 238000010992 reflux Methods 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- 239000003208 petroleum Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 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
- 239000012043 crude product Substances 0.000 description 14
- 239000012074 organic phase Substances 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
- 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 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 241000699670 Mus sp. Species 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
- 238000001704 evaporation Methods 0.000 description 11
- 230000008020 evaporation Effects 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000006186 oral dosage form Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 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
- 239000012267 brine 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
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- 239000010931 gold Substances 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 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
- 229920002472 Starch Polymers 0.000 description 5
- 239000001961 anticonvulsive agent Substances 0.000 description 5
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- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 5
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- 239000004615 ingredient Substances 0.000 description 5
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- 239000008107 starch Substances 0.000 description 5
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- 125000001424 substituent group Chemical group 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
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- 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
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- A61P25/00—Drugs for disorders of the nervous system
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| EP0915875B1 (en) | 1996-07-25 | 2003-04-09 | MERCK SHARP & DOHME LTD. | Substituted triazolo-pyridazine derivatives as ligands for gaba receptors |
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| 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 |
| DE69936998T2 (de) | 1998-10-16 | 2008-05-21 | Merck Sharp & Dohme Ltd., Hoddesdon | Pyrazolotriazinderivate als gaba-rezeptorliganden |
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| NZ523807A (en) * | 2000-06-30 | 2004-09-24 | 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 |
| EA009902B1 (ru) | 2004-02-13 | 2008-04-28 | УОРНЕР-ЛАМБЕРТ КОМПАНИ Эл-Эл-Си | Модуляторы рецепторов андрогенов |
| JP2007532621A (ja) | 2004-04-13 | 2007-11-15 | ワーナー−ランバート カンパニー リミテッド ライアビリティー カンパニー | アンドロゲンモジュレータ |
| BRPI0509980A (pt) | 2004-04-22 | 2007-10-16 | Warner Lambert Co | moduladores de androgênio |
| TW200724139A (en) | 2005-05-05 | 2007-07-01 | Warner Lambert Co | Androgen modulators |
| HRP20140195T1 (hr) | 2008-08-29 | 2014-04-11 | Concert Pharmaceuticals Inc. | Supstituirani derivati triazolopiridazina |
| 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 |
| EP2414365B1 (en) | 2009-04-01 | 2013-12-25 | Aniona ApS | SUBSTITUTED [1,2,4¨TRIAZOLO[1,5-a]PYRIMIDINES AND THEIR USE AS POTASSIUM CHANNEL MODULATORS |
| WO2010112485A1 (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 |
| 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 CA CA002173857A patent/CA2173857A1/en not_active Abandoned
- 1994-10-12 WO PCT/EP1994/003364 patent/WO1995010521A1/en not_active Ceased
- 1994-10-12 JP JP7511287A patent/JPH09503771A/ja not_active Ceased
- 1994-10-12 HU HU9600959A patent/HUT74580A/hu unknown
- 1994-10-12 PL PL94313970A patent/PL177920B1/pl unknown
- 1994-10-12 EP EP94929537A patent/EP0723546B1/en not_active Expired - Lifetime
- 1994-10-12 UA UA96041428A patent/UA42738C2/uk unknown
- 1994-10-12 ZA ZA947949A patent/ZA947949B/xx unknown
- 1994-10-12 RU RU96108927A patent/RU2136684C1/ru active
- 1994-10-12 DK DK94929537T patent/DK0723546T3/da active
- 1994-10-12 ES ES94929537T patent/ES2142413T3/es not_active Expired - Lifetime
- 1994-10-12 CN CN94194265A patent/CN1040537C/zh not_active Expired - Fee Related
- 1994-10-12 US US08/628,662 patent/US5753665A/en not_active Expired - Lifetime
- 1994-10-12 NZ NZ274500A patent/NZ274500A/en unknown
- 1994-10-12 AU AU78554/94A patent/AU679573B2/en not_active Ceased
- 1994-10-12 DE DE69422724T patent/DE69422724T2/de not_active Expired - Lifetime
- 1994-10-12 CZ CZ961069A patent/CZ106996A3/cs unknown
- 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 AT AT94929537T patent/ATE188966T1/de not_active IP Right Cessation
- 1994-10-12 BR BR9407812A patent/BR9407812A/pt not_active Application Discontinuation
- 1994-10-12 PT PT94929537T patent/PT723546E/pt unknown
- 1994-10-12 SK SK437-96A patent/SK282329B6/sk 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/FI961630A7/fi unknown
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2000
- 2000-01-26 GR GR20000400175T patent/GR3032480T3/el not_active IP Right Cessation
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