CA2173857A1 - Therapeutic agents - Google Patents
Therapeutic agentsInfo
- Publication number
- CA2173857A1 CA2173857A1 CA002173857A CA2173857A CA2173857A1 CA 2173857 A1 CA2173857 A1 CA 2173857A1 CA 002173857 A CA002173857 A CA 002173857A CA 2173857 A CA2173857 A CA 2173857A CA 2173857 A1 CA2173857 A1 CA 2173857A1
- Authority
- CA
- Canada
- Prior art keywords
- triazolo
- ethyl
- pyrimidine
- formula
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003814 drug Substances 0.000 title claims description 10
- 229940124597 therapeutic agent Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 268
- -1 cyano, hydroxy Chemical group 0.000 claims abstract description 59
- 125000005843 halogen group Chemical group 0.000 claims abstract description 38
- 206010010904 Convulsion Diseases 0.000 claims abstract description 31
- 238000000034 method Methods 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 230000006378 damage Effects 0.000 claims abstract description 15
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 14
- 230000000926 neurological effect Effects 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
- 206010019196 Head injury Diseases 0.000 claims abstract description 11
- 208000032843 Hemorrhage Diseases 0.000 claims abstract description 11
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 11
- 208000006011 Stroke Diseases 0.000 claims abstract description 11
- 208000030886 Traumatic Brain injury Diseases 0.000 claims abstract description 11
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 11
- 206010015037 epilepsy Diseases 0.000 claims abstract description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 238000011321 prophylaxis Methods 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 230000008569 process Effects 0.000 claims abstract description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 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
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 17
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 9
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims description 32
- 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 16
- 241001465754 Metazoa Species 0.000 claims description 13
- 241000282414 Homo sapiens Species 0.000 claims description 11
- 150000001298 alcohols Chemical class 0.000 claims description 9
- 238000002560 therapeutic procedure Methods 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 6
- 239000003377 acid catalyst Substances 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
- 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
- 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
- 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
- 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 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
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 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
- 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 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
- 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 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 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 239000007822 coupling agent Substances 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 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 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 150000002989 phenols Chemical class 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
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 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 2
- 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 2
- 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 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 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 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
- 239000000203 mixture Substances 0.000 description 149
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 127
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 65
- 239000000243 solution Substances 0.000 description 61
- 239000002904 solvent Substances 0.000 description 61
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 59
- 238000012360 testing method Methods 0.000 description 55
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- 229940093499 ethyl acetate Drugs 0.000 description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 235000019439 ethyl acetate Nutrition 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 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 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- 241000699670 Mus sp. Species 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 235000002639 sodium chloride Nutrition 0.000 description 22
- 238000001953 recrystallisation Methods 0.000 description 21
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 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
- 239000003480 eluent 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
- 238000001914 filtration Methods 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 15
- 239000012043 crude product Substances 0.000 description 14
- 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
- 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
- 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
- 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
- 239000007864 aqueous solution Substances 0.000 description 11
- 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
- 239000012362 glacial acetic acid Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 239000000839 emulsion Substances 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000003818 flash chromatography Methods 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
- 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
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 7
- 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 7
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000001961 anticonvulsive agent Substances 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 229960004132 diethyl ether Drugs 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- DEIBXAPEZDJDRC-UHFFFAOYSA-M (dimethylaminomethylideneamino)methylidene-dimethylazanium;chloride Chemical compound [Cl-].CN(C)C=NC=[N+](C)C DEIBXAPEZDJDRC-UHFFFAOYSA-M 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
- 229960003965 antiepileptics Drugs 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 150000001721 carbon Chemical group 0.000 description 6
- 239000000284 extract 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
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
- 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 5
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 5
- 239000003995 emulsifying agent Substances 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
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 239000002674 ointment Substances 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 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
- IYGYMKDQCDOMRE-UHFFFAOYSA-N d-Bicucullin Natural products CN1CCC2=CC=3OCOC=3C=C2C1C1OC(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000003301 hydrolyzing effect Effects 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 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
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- 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)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9321162.1 | 1993-10-13 | ||
| GB939321162A GB9321162D0 (en) | 1993-10-13 | 1993-10-13 | Therapeutic agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2173857A1 true CA2173857A1 (en) | 1995-04-20 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002173857A Abandoned CA2173857A1 (en) | 1993-10-13 | 1994-10-12 | Therapeutic agents |
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| EP (1) | EP0723546B1 (https=) |
| JP (1) | JPH09503771A (https=) |
| CN (1) | CN1040537C (https=) |
| AT (1) | ATE188966T1 (https=) |
| AU (1) | AU679573B2 (https=) |
| BG (1) | BG62405B1 (https=) |
| BR (1) | BR9407812A (https=) |
| CA (1) | CA2173857A1 (https=) |
| CZ (1) | CZ106996A3 (https=) |
| DE (1) | DE69422724T2 (https=) |
| DK (1) | DK0723546T3 (https=) |
| ES (1) | ES2142413T3 (https=) |
| FI (1) | FI961630A0 (https=) |
| GB (1) | GB9321162D0 (https=) |
| GR (1) | GR3032480T3 (https=) |
| HU (1) | HUT74580A (https=) |
| IL (1) | IL111259A (https=) |
| IN (1) | IN179169B (https=) |
| MY (1) | MY112110A (https=) |
| NO (1) | NO306509B1 (https=) |
| NZ (1) | NZ274500A (https=) |
| PL (1) | PL177920B1 (https=) |
| PT (1) | PT723546E (https=) |
| RO (1) | RO117020B1 (https=) |
| RU (1) | RU2136684C1 (https=) |
| SK (1) | SK282329B6 (https=) |
| TW (1) | TW372237B (https=) |
| UA (1) | UA42738C2 (https=) |
| WO (1) | WO1995010521A1 (https=) |
| ZA (1) | ZA947949B (https=) |
Families Citing this family (25)
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| 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 |
| ES2194205T3 (es) | 1996-07-25 | 2003-11-16 | Merck Sharp & Dohme | Derivados de triazolo-piridazina sustituidos como ligandos para los receptores gaba. |
| 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 |
| CA2346289A1 (en) * | 1998-10-16 | 2000-04-27 | Merck Sharp & Dohme Limited | Pyrazolo-triazine derivatives as ligands for gaba receptors |
| GB9906126D0 (en) * | 1999-03-18 | 1999-05-12 | Knoll Ag | Pharmaceutical formulations |
| 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 |
| GB9914743D0 (en) * | 1999-06-24 | 1999-08-25 | Knoll Ag | Therapeutic agents |
| AU2001273062B2 (en) * | 2000-06-30 | 2005-11-24 | Wyeth | 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 |
| KR100783255B1 (ko) | 2004-02-13 | 2007-12-06 | 워너-램버트 캄파니 엘엘씨 | 안드로젠 수용체 조절제 |
| 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 |
| 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 |
| CA2735549A1 (en) | 2008-08-29 | 2010-03-04 | Concert Pharmaceuticals, Inc. | Substituted triazolo-pyridazine derivatives |
| EP2438069A1 (en) | 2009-04-01 | 2012-04-11 | NeuroSearch A/S | Substituted [1,2,4]triazolo[1,5-a]pyrimidines and their use as potassium channel modulators |
| 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 |
| EP3969639B1 (en) | 2019-05-13 | 2025-03-12 | 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 SK SK437-96A patent/SK282329B6/sk unknown
- 1994-10-12 AT AT94929537T patent/ATE188966T1/de not_active IP Right Cessation
- 1994-10-12 CN CN94194265A patent/CN1040537C/zh not_active Expired - Fee Related
- 1994-10-12 ES ES94929537T patent/ES2142413T3/es not_active Expired - Lifetime
- 1994-10-12 EP EP94929537A patent/EP0723546B1/en not_active Expired - Lifetime
- 1994-10-12 PL PL94313970A patent/PL177920B1/pl unknown
- 1994-10-12 JP JP7511287A patent/JPH09503771A/ja not_active Ceased
- 1994-10-12 DE DE69422724T patent/DE69422724T2/de not_active Expired - Lifetime
- 1994-10-12 BR BR9407812A patent/BR9407812A/pt not_active Application Discontinuation
- 1994-10-12 US US08/628,662 patent/US5753665A/en not_active Expired - Lifetime
- 1994-10-12 RU RU96108927A patent/RU2136684C1/ru active
- 1994-10-12 WO PCT/EP1994/003364 patent/WO1995010521A1/en not_active Ceased
- 1994-10-12 HU HU9600959A patent/HUT74580A/hu unknown
- 1994-10-12 PT PT94929537T patent/PT723546E/pt unknown
- 1994-10-12 CA CA002173857A patent/CA2173857A1/en not_active Abandoned
- 1994-10-12 IL IL111259A patent/IL111259A/en not_active IP Right Cessation
- 1994-10-12 AU AU78554/94A patent/AU679573B2/en not_active Ceased
- 1994-10-12 CZ CZ961069A patent/CZ106996A3/cs unknown
- 1994-10-12 ZA ZA947949A patent/ZA947949B/xx unknown
- 1994-10-12 RO RO96-00795A patent/RO117020B1/ro unknown
- 1994-10-12 UA UA96041428A patent/UA42738C2/uk unknown
- 1994-10-12 NZ NZ274500A patent/NZ274500A/en 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
-
2000
- 2000-01-26 GR GR20000400175T patent/GR3032480T3/el not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |