HUT74580A - Triazolo[1,5-a]pyrimidine derivatives, proless for producing them and pharmaceutical compositions containing them - Google Patents
Triazolo[1,5-a]pyrimidine derivatives, proless for producing them and pharmaceutical compositions containing them Download PDFInfo
- Publication number
- HUT74580A HUT74580A HU9600959A HU9600959A HUT74580A HU T74580 A HUT74580 A HU T74580A HU 9600959 A HU9600959 A HU 9600959A HU 9600959 A HU9600959 A HU 9600959A HU T74580 A HUT74580 A HU T74580A
- Authority
- HU
- Hungary
- Prior art keywords
- pyrimidine
- ethyl
- triazolo
- phenoxy
- formula
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 20
- POFDSYGXHVPQNX-UHFFFAOYSA-N triazolo[1,5-a]pyrimidine Chemical class C1=CC=NC2=CN=NN21 POFDSYGXHVPQNX-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 192
- -1 cyano, hydroxy Chemical group 0.000 claims description 86
- 239000001257 hydrogen Substances 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 150000002367 halogens Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical group 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 19
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 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 4
- 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 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 3
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 3
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 3
- XAGZJIQIVXSURR-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]piperidin-2-one Chemical group C1=CC(C(F)(F)F)=CC=C1N1C(=O)CCCC1 XAGZJIQIVXSURR-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
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 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 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
- 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 2
- 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 2
- 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 2
- 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 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 description 2
- 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 2
- 206010029897 Obsessive thoughts Diseases 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 2
- 229910052731 fluorine Inorganic materials 0.000 claims 2
- 239000011737 fluorine Substances 0.000 claims 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
- 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 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
- RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 claims 1
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- 239000000203 mixture Substances 0.000 description 102
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- 239000000243 solution Substances 0.000 description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
- 239000002904 solvent Substances 0.000 description 60
- 239000004480 active ingredient Substances 0.000 description 57
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 56
- 238000012360 testing method Methods 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 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 31
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 27
- 239000000047 product Substances 0.000 description 27
- 238000003756 stirring Methods 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 206010010904 Convulsion Diseases 0.000 description 21
- 241000699670 Mus sp. Species 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
- 238000010992 reflux Methods 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
- 239000003208 petroleum Substances 0.000 description 18
- 239000000725 suspension Substances 0.000 description 17
- 241001465754 Metazoa Species 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 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
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000012362 glacial acetic acid Substances 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 239000002775 capsule Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- 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 10
- 125000006083 1-bromoethyl group Chemical group 0.000 description 9
- 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
- 238000002360 preparation method Methods 0.000 description 9
- 208000012902 Nervous system disease Diseases 0.000 description 8
- 208000025966 Neurological disease Diseases 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 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
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 230000000740 bleeding effect Effects 0.000 description 7
- 150000001721 carbon Chemical group 0.000 description 7
- 206010015037 epilepsy Diseases 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000000926 neurological effect Effects 0.000 description 7
- 239000006186 oral dosage form Substances 0.000 description 7
- 239000012265 solid product Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 6
- 206010019196 Head injury Diseases 0.000 description 6
- 208000032843 Hemorrhage Diseases 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
- 208000006011 Stroke Diseases 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 208000034158 bleeding Diseases 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
- 125000000547 substituted alkyl group Chemical group 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 241000282412 Homo Species 0.000 description 5
- 239000001961 anticonvulsive agent Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 208000029028 brain injury Diseases 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 238000009472 formulation Methods 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
- 239000000463 material Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000002674 ointment Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-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
- 239000003377 acid catalyst Substances 0.000 description 4
- 230000001773 anti-convulsant effect Effects 0.000 description 4
- 229960003965 antiepileptics Drugs 0.000 description 4
- AACMFFIUYXGCOC-UHFFFAOYSA-N bicuculline Natural products CN1CCc2cc3OCOc3cc2C1C4OCc5c6OCOc6ccc45 AACMFFIUYXGCOC-UHFFFAOYSA-N 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 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
- 230000000694 effects Effects 0.000 description 4
- 239000003995 emulsifying agent Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 230000003287 optical 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
- 230000002265 prevention Effects 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 239000012049 topical pharmaceutical composition Substances 0.000 description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- YCDOHSUMKPOXSR-UHFFFAOYSA-N 1-chloro-4-methylpent-1-en-3-one Chemical compound CC(C)C(=O)C=CCl YCDOHSUMKPOXSR-UHFFFAOYSA-N 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
- 239000001828 Gelatine Substances 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
- 238000001030 gas--liquid chromatography Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 235000019271 petrolatum Nutrition 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
- 239000012485 toluene extract Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 2
- HYBSAHPNXCCSOM-CMDGGOBGSA-N (e)-4-(4-chlorophenoxy)-1-(dimethylamino)pent-1-en-3-one Chemical compound CN(C)/C=C/C(=O)C(C)OC1=CC=C(Cl)C=C1 HYBSAHPNXCCSOM-CMDGGOBGSA-N 0.000 description 2
- BCCIHUVTZHAYAY-UHFFFAOYSA-N 1,1-dichloro-4-methylpentan-3-one Chemical compound CC(C)C(=O)CC(Cl)Cl BCCIHUVTZHAYAY-UHFFFAOYSA-N 0.000 description 2
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical group C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 2
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JLIDVCMBCGBIEY-UHFFFAOYSA-N 1-penten-3-one Chemical compound CCC(=O)C=C JLIDVCMBCGBIEY-UHFFFAOYSA-N 0.000 description 2
- NBSVIJGYSGSBFV-UHFFFAOYSA-N 3-(4-chlorophenoxy)pentan-2-one Chemical compound CCC(C(C)=O)OC1=CC=C(Cl)C=C1 NBSVIJGYSGSBFV-UHFFFAOYSA-N 0.000 description 2
- QVKRDNMNSHRBKK-UHFFFAOYSA-N 3-oxobutan-2-yl benzoate Chemical compound CC(=O)C(C)OC(=O)C1=CC=CC=C1 QVKRDNMNSHRBKK-UHFFFAOYSA-N 0.000 description 2
- TXFPEBPIARQUIG-UHFFFAOYSA-N 4'-hydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1 TXFPEBPIARQUIG-UHFFFAOYSA-N 0.000 description 2
- DPCNJKAZDVOVPS-UHFFFAOYSA-N 4-(4-chlorophenoxy)-1-(dimethylamino)hex-1-en-3-one Chemical compound CN(C)C=CC(=O)C(CC)OC1=CC=C(Cl)C=C1 DPCNJKAZDVOVPS-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000006751 Mitsunobu reaction Methods 0.000 description 2
- 208000007101 Muscle Cramp Diseases 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- KWJICKXTDKWMCI-UHFFFAOYSA-N [5-(dimethylamino)-3-oxopent-4-en-2-yl] benzoate Chemical compound CN(C)C=CC(=O)C(C)OC(=O)C1=CC=CC=C1 KWJICKXTDKWMCI-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000002921 anti-spasmodic effect Effects 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 229960001701 chloroform Drugs 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000013101 initial test Methods 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 description 1
- DEIBXAPEZDJDRC-UHFFFAOYSA-M (dimethylaminomethylideneamino)methylidene-dimethylazanium;chloride Chemical compound [Cl-].CN(C)C=NC=[N+](C)C DEIBXAPEZDJDRC-UHFFFAOYSA-M 0.000 description 1
- LFHLBTPPLHEZBM-VOTSOKGWSA-N (e)-4-(2,4-dichlorophenoxy)-1-(dimethylamino)pent-1-en-3-one Chemical compound CN(C)/C=C/C(=O)C(C)OC1=CC=C(Cl)C=C1Cl LFHLBTPPLHEZBM-VOTSOKGWSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- HFDIJTIPFVXOED-UHFFFAOYSA-N 1,4-dichlorobut-3-en-2-one Chemical compound ClCC(=O)C=CCl HFDIJTIPFVXOED-UHFFFAOYSA-N 0.000 description 1
- CFMFGANUEMXVTA-UHFFFAOYSA-N 1-chloropent-1-en-3-one Chemical compound CCC(=O)C=CCl CFMFGANUEMXVTA-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 1
- PAWQVTBBRAZDMG-UHFFFAOYSA-N 2-(3-bromo-2-fluorophenyl)acetic acid Chemical compound OC(=O)CC1=CC=CC(Br)=C1F PAWQVTBBRAZDMG-UHFFFAOYSA-N 0.000 description 1
- IGYXYGDEYHNFFT-UHFFFAOYSA-N 2-chloro-4-fluorophenol Chemical compound OC1=CC=C(F)C=C1Cl IGYXYGDEYHNFFT-UHFFFAOYSA-N 0.000 description 1
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
- WDNBURPWRNALGP-UHFFFAOYSA-N 3,4-Dichlorophenol Chemical compound OC1=CC=C(Cl)C(Cl)=C1 WDNBURPWRNALGP-UHFFFAOYSA-N 0.000 description 1
- CIJAAXYQLAJGGN-UHFFFAOYSA-N 3-(2,4-dichlorophenoxy)butan-2-one Chemical compound CC(=O)C(C)OC1=CC=C(Cl)C=C1Cl CIJAAXYQLAJGGN-UHFFFAOYSA-N 0.000 description 1
- UXTBBGMAUUPHCT-UHFFFAOYSA-N 3-(4-chlorophenoxy)butan-2-one Chemical compound CC(=O)C(C)OC1=CC=C(Cl)C=C1 UXTBBGMAUUPHCT-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- OIMRLHCSLQUXLL-UHFFFAOYSA-N 3-chlorobutan-2-one Chemical compound CC(Cl)C(C)=O OIMRLHCSLQUXLL-UHFFFAOYSA-N 0.000 description 1
- CKSIBFLEDRJUTN-UHFFFAOYSA-N 3-chloropentan-2-one Chemical compound CCC(Cl)C(C)=O CKSIBFLEDRJUTN-UHFFFAOYSA-N 0.000 description 1
- HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 description 1
- 239000003140 4 aminobutyric acid A receptor blocking agent Substances 0.000 description 1
- QASBCTGZKABPKX-UHFFFAOYSA-N 4-(methylsulfanyl)phenol Chemical compound CSC1=CC=C(O)C=C1 QASBCTGZKABPKX-UHFFFAOYSA-N 0.000 description 1
- WDRJNKMAZMEYOF-UHFFFAOYSA-N 4-(trifluoromethoxy)phenol Chemical compound OC1=CC=C(OC(F)(F)F)C=C1 WDRJNKMAZMEYOF-UHFFFAOYSA-N 0.000 description 1
- BAYGVMXZJBFEMB-UHFFFAOYSA-N 4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1 BAYGVMXZJBFEMB-UHFFFAOYSA-N 0.000 description 1
- GZFGOTFRPZRKDS-UHFFFAOYSA-N 4-bromophenol Chemical compound OC1=CC=C(Br)C=C1 GZFGOTFRPZRKDS-UHFFFAOYSA-N 0.000 description 1
- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 1
- FMIHFTDZEIOVQX-UHFFFAOYSA-N 4-ethylsulfanylphenol Chemical compound CCSC1=CC=C(O)C=C1 FMIHFTDZEIOVQX-UHFFFAOYSA-N 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- 229940073735 4-hydroxy acetophenone Drugs 0.000 description 1
- WXVQCFALDUVKSC-UHFFFAOYSA-N 5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound N1=C(C)C=C(C)N2N=CN=C21 WXVQCFALDUVKSC-UHFFFAOYSA-N 0.000 description 1
- FJRZOOICEHBAED-UHFFFAOYSA-N 5-methyl-1h-1,2,4-triazol-3-amine Chemical compound CC1=NNC(N)=N1 FJRZOOICEHBAED-UHFFFAOYSA-N 0.000 description 1
- IFRARRVHGDDLEJ-UHFFFAOYSA-N 7-(1-chloroethyl)-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound CC(Cl)C1=CC=NC2=NC=NN12 IFRARRVHGDDLEJ-UHFFFAOYSA-N 0.000 description 1
- DUHYKSPOPOOTKO-UHFFFAOYSA-N 7-(chloromethyl)-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound ClCC1=CC=NC2=NC=NN12 DUHYKSPOPOOTKO-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 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 description 1
- YZCWFIZTCBZJSM-UHFFFAOYSA-N 7-ethyl-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound CCC1=CC=NC2=NC=NN12 YZCWFIZTCBZJSM-UHFFFAOYSA-N 0.000 description 1
- WWMNFWLAYLFNOQ-UHFFFAOYSA-N 7-propan-2-yl-[1,2,4]triazolo[1,5-a]pyrimidine Chemical compound CC(C)C1=CC=NC2=NC=NN12 WWMNFWLAYLFNOQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- IYGYMKDQCDOMRE-QRWMCTBCSA-N Bicculine Chemical compound O([C@H]1C2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-QRWMCTBCSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 240000005702 Galium aparine Species 0.000 description 1
- 235000014820 Galium aparine Nutrition 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000008238 Muscle Spasticity Diseases 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 235000019486 Sunflower oil Nutrition 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- BZHJMEDXRYGGRV-UHFFFAOYSA-N Vinyl chloride Chemical group ClC=C BZHJMEDXRYGGRV-UHFFFAOYSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- SRNKZYRMFBGSGE-UHFFFAOYSA-N [1,2,4]triazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CN=C21 SRNKZYRMFBGSGE-UHFFFAOYSA-N 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000012042 active reagent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 229950003476 aminothiazole Drugs 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- WURBFLDFSFBTLW-UHFFFAOYSA-N benzil Chemical group C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 WURBFLDFSFBTLW-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000012084 conversion product Substances 0.000 description 1
- 239000003179 convulsant agent Substances 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 239000011928 denatured alcohol Substances 0.000 description 1
- 229940075894 denatured ethanol Drugs 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- LOZWAPSEEHRYPG-UHFFFAOYSA-N dithiane Natural products C1CSCCS1 LOZWAPSEEHRYPG-UHFFFAOYSA-N 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- SAXHIDRUJXPDOD-SECBINFHSA-N ethyl (2R)-hydroxy(phenyl)acetate Chemical compound CCOC(=O)[C@H](O)C1=CC=CC=C1 SAXHIDRUJXPDOD-SECBINFHSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- CGAJYBUEWWHRDO-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate;triphenylphosphane Chemical compound CCOC(=O)N=NC(=O)OCC.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CGAJYBUEWWHRDO-UHFFFAOYSA-N 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000010685 fatty oil Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000002307 glutamic acids Chemical class 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229940116364 hard fat Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 235000005772 leucine Nutrition 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004460 liquid liquid chromatography Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical group [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-N methyl sulfate Chemical compound COS(O)(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-N 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- FLESAADTDNKLFJ-UHFFFAOYSA-N nickel;pentane-2,4-dione Chemical compound [Ni].CC(=O)CC(C)=O FLESAADTDNKLFJ-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002829 nitrogen Chemical group 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 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
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 208000018198 spasticity Diseases 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 239000008009 topical excipient Substances 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
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)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (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)
- 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 (2)
| Publication Number | Publication Date |
|---|---|
| HU9600959D0 HU9600959D0 (en) | 1996-06-28 |
| HUT74580A true HUT74580A (en) | 1997-01-28 |
Family
ID=10743505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9600959A HUT74580A (en) | 1993-10-13 | 1994-10-12 | Triazolo[1,5-a]pyrimidine derivatives, proless for producing them and pharmaceutical compositions containing them |
Country Status (31)
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 |
| CZ18199A3 (cs) | 1996-07-25 | 1999-06-16 | Merck Sharp And Dohme Limited | Triazolopyridazinové deriváty, způsob výroby a farmaceutický prostředek |
| 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 |
| 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 |
| HK1052646A1 (zh) * | 2000-06-30 | 2003-09-26 | Wyeth | 替代三氮苯(triazolopyrimidines)作为抗癌剂 |
| 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 |
| WO2005080320A1 (en) | 2004-02-13 | 2005-09-01 | Warner-Lambert Company Llc | Androgen receptor modulators |
| EP1737813A1 (en) | 2004-04-13 | 2007-01-03 | Warner-Lambert Company LLC | Androgen modulators |
| 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 |
| PL2328414T3 (pl) | 2008-08-29 | 2014-05-30 | Concert Pharmaceuticals Inc | Podstawione pochodne triazolo-pirydazyny |
| EP2414364A1 (en) * | 2009-04-01 | 2012-02-08 | NeuroSearch A/S | SUBSTITUTED Ý1,2,4¨TRIAZOLOÝ1,5-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 |
| WO2010112486A1 (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 |
| 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 UA UA96041428A patent/UA42738C2/uk unknown
- 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 AT AT94929537T patent/ATE188966T1/de not_active IP Right Cessation
- 1994-10-12 WO PCT/EP1994/003364 patent/WO1995010521A1/en not_active Application Discontinuation
- 1994-10-12 DE DE69422724T patent/DE69422724T2/de not_active Expired - Lifetime
- 1994-10-12 JP JP7511287A patent/JPH09503771A/ja not_active Ceased
- 1994-10-12 CZ CZ961069A patent/CZ106996A3/cs unknown
- 1994-10-12 IL IL111259A patent/IL111259A/en not_active IP Right Cessation
- 1994-10-12 ZA ZA947949A patent/ZA947949B/xx unknown
- 1994-10-12 RO RO96-00795A patent/RO117020B1/ro unknown
- 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 PT PT94929537T patent/PT723546E/pt unknown
- 1994-10-12 PL PL94313970A patent/PL177920B1/pl unknown
- 1994-10-12 ES ES94929537T patent/ES2142413T3/es not_active Expired - Lifetime
- 1994-10-12 DK DK94929537T patent/DK0723546T3/da active
- 1994-10-12 CA CA002173857A patent/CA2173857A1/en not_active Abandoned
- 1994-10-12 HU HU9600959A patent/HUT74580A/hu unknown
- 1994-10-12 RU RU96108927A patent/RU2136684C1/ru active
- 1994-10-12 EP EP94929537A patent/EP0723546B1/en not_active Expired - Lifetime
- 1994-10-12 SK SK437-96A patent/SK282329B6/sk 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/FI961630A7/fi unknown
-
2000
- 2000-01-26 GR GR20000400175T patent/GR3032480T3/el not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HUT74580A (en) | Triazolo[1,5-a]pyrimidine derivatives, proless for producing them and pharmaceutical compositions containing them | |
| KR100911073B1 (ko) | 이미다졸 유도체의 결정 형태 | |
| LU85743A1 (fr) | Composes heterocycliques | |
| US4734421A (en) | Anti-inflammatory substituted 2-benzyl-mercapto-imidazole and pyrimidine derivatives compositions and method of use therefor | |
| EP1242069B1 (en) | Albumin-binding compounds that prevent nonenzymatic glycation and that may be used for treatment of glycation-related pathologies | |
| PL188649B1 (pl) | Kompozycje farmaceutyczna do leczenia chorób, w których mediatorem jest cyklooksygenaza-2, zawierająca 3-fenylo-4-(4-(metylosulfonylo)fenylo)-2(5H)-furanon oraz zastosowanie 3-fenylo-4-(4-(metylosulfonylo)fenylo)-2(5H)-furanonu | |
| LU85248A1 (fr) | Derives de thiazolidine,procede pour leur preparation et compositions pharmaceutiques les contenant | |
| US5905079A (en) | 1,2,4-triazolo 4,3-b!pyridazine derivatives and their use | |
| PL154186B1 (en) | Method for manufacturing arylic derivatives of the hydroxamic acid | |
| US4694018A (en) | Substituted 1,5-diphenyl-2-pyrrolepropionic acids and derivatives | |
| DE2234651A1 (de) | Eckige klammer auf 1-(p-chlorbenzoyl)5-methoxy-2-methyl-3-indol eckige klammer zu acetoxyessigsaeure, verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln | |
| JP3585045B2 (ja) | ミトコンドリア疾病の処置におけるリルゾールの適用 | |
| FR2460947A1 (fr) | Nouveau derives n-substitues du tetrahydropyridinyl-indole, leurs sels, procede de preparation, application a titre de medicaments et compositions les renfermant | |
| FR2499981A1 (fr) | Acides amino-2 halogenobenzoyl-3 methylphenylacetiques et leurs esters et sels utiles comme medicaments anti-inflammatoires et analgesiques | |
| JP2003503343A (ja) | 治療剤 | |
| HU193360B (en) | Process for producing /amino-pyridinyl/- and /nitro-pyridinyl/-amino-phenyl/-aryl-methanone derivatives | |
| IE904248A1 (en) | Therapeutically active fluoro substituted benzimidazoles,¹processes for their preparation as well as their use | |
| JP2002540110A (ja) | トリアゾロピロミジノール化合物及びその塩 | |
| HUT55027A (en) | Process for producing new inozine- and guanozine derivatives and pharmaceutical compositions containing them as active components |