IL111259A - Pharmaceutical preparations containing 7-phenoxy, cyclo (alkyl) 1,2,4 [triazolo] A1,5 [pyrimidine Certain new compounds of this type and their preparation - Google Patents
Pharmaceutical preparations containing 7-phenoxy, cyclo (alkyl) 1,2,4 [triazolo] A1,5 [pyrimidine Certain new compounds of this type and their preparationInfo
- Publication number
- IL111259A IL111259A IL111259A IL11125994A IL111259A IL 111259 A IL111259 A IL 111259A IL 111259 A IL111259 A IL 111259A IL 11125994 A IL11125994 A IL 11125994A IL 111259 A IL111259 A IL 111259A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- compounds
- compound
- independently represent
- mixture
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 266
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 30
- 238000002360 preparation method Methods 0.000 title claims description 15
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title description 26
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title description 2
- -1 cyano, hydroxy Chemical group 0.000 claims abstract description 56
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 230000000926 neurological effect Effects 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 14
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 13
- 230000006378 damage Effects 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 206010019196 Head injury Diseases 0.000 claims abstract description 11
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 11
- 206010015037 epilepsy Diseases 0.000 claims abstract description 11
- 238000011321 prophylaxis Methods 0.000 claims abstract description 11
- 208000032843 Hemorrhage Diseases 0.000 claims abstract description 10
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims description 151
- 238000000034 method Methods 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 241000282414 Homo sapiens Species 0.000 claims description 10
- 150000001298 alcohols Chemical class 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 4
- 239000003377 acid catalyst Substances 0.000 claims description 3
- 150000001450 anions Chemical class 0.000 claims description 3
- 230000008878 coupling Effects 0.000 claims description 3
- 238000010168 coupling process Methods 0.000 claims description 3
- 238000005859 coupling reaction Methods 0.000 claims description 3
- 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 210000004556 brain Anatomy 0.000 claims 2
- 206010010904 Convulsion Diseases 0.000 abstract description 29
- 125000005843 halogen group Chemical group 0.000 abstract description 29
- 125000001589 carboacyl group Chemical group 0.000 abstract description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 9
- 208000006011 Stroke Diseases 0.000 abstract description 9
- 208000030886 Traumatic Brain injury Diseases 0.000 abstract description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 abstract description 8
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 74
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 65
- 239000002904 solvent Substances 0.000 description 61
- 238000012360 testing method Methods 0.000 description 55
- 239000000243 solution Substances 0.000 description 54
- 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 45
- 229940093499 ethyl acetate Drugs 0.000 description 43
- 235000019439 ethyl acetate Nutrition 0.000 description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 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
- 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
- 239000007864 aqueous solution Substances 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
- 239000000725 suspension Substances 0.000 description 17
- 239000003921 oil 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
- 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 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
- 238000003818 flash chromatography Methods 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 125000004414 alkyl thio group Chemical group 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
- 230000000694 effects Effects 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
- 239000001961 anticonvulsive agent Substances 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 150000001721 carbon Chemical group 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
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- 230000001773 anti-convulsant effect Effects 0.000 description 6
- 229960003965 antiepileptics Drugs 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 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
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 5
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 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 4
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- 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 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
- 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
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
- 238000011200 topical administration Methods 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 125000006083 1-bromoethyl group Chemical group 0.000 description 3
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-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
- 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 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
- 125000004423 acyloxy group Chemical group 0.000 description 3
- 125000005236 alkanoylamino group Chemical group 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- IYGYMKDQCDOMRE-ZWKOTPCHSA-N bicuculline Chemical compound O([C@H]1[C@@H]2C3=CC=4OCOC=4C=C3CCN2C)C(=O)C2=C1C=CC1=C2OCO1 IYGYMKDQCDOMRE-ZWKOTPCHSA-N 0.000 description 3
- 239000007894 caplet Substances 0.000 description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 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 3
- 238000001640 fractional crystallisation Methods 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
- 238000001030 gas--liquid chromatography Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 230000002140 halogenating effect Effects 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
- 235000019271 petrolatum Nutrition 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
- 125000000547 substituted alkyl group Chemical group 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- 239000012485 toluene extract Substances 0.000 description 3
- 239000012049 topical pharmaceutical composition Substances 0.000 description 3
- 239000001993 wax Substances 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000001478 1-chloroethyl group Chemical group [H]C([H])([H])C([H])(Cl)* 0.000 description 2
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-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
- LFHLBTPPLHEZBM-UHFFFAOYSA-N 4-(2,4-dichlorophenoxy)-1-(dimethylamino)pent-1-en-3-one Chemical compound CN(C)C=CC(=O)C(C)OC1=CC=C(Cl)C=C1Cl LFHLBTPPLHEZBM-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
- 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 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 description 2
- 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 description 2
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- 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
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- 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
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- 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
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
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- 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
- 230000002265 prevention Effects 0.000 description 1
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- 238000006722 reduction 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
- 239000003352 sequestering agent Substances 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
- 239000001632 sodium acetate Substances 0.000 description 1
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- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 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
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
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- 230000003019 stabilising effect Effects 0.000 description 1
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- 239000005720 sucrose Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 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
- 230000005062 synaptic transmission Effects 0.000 description 1
- 229920003002 synthetic resin Polymers 0.000 description 1
- 239000000057 synthetic resin Substances 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001256 tonic effect Effects 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
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- 239000002023 wood Substances 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)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939321162A GB9321162D0 (en) | 1993-10-13 | 1993-10-13 | Therapeutic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL111259A0 IL111259A0 (en) | 1995-03-30 |
| IL111259A true IL111259A (en) | 1998-02-08 |
Family
ID=10743505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL111259A IL111259A (en) | 1993-10-13 | 1994-10-12 | Pharmaceutical preparations containing 7-phenoxy, cyclo (alkyl) 1,2,4 [triazolo] A1,5 [pyrimidine Certain new compounds of this type and their preparation |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US5753665A (zh) |
| EP (1) | EP0723546B1 (zh) |
| JP (1) | JPH09503771A (zh) |
| CN (1) | CN1040537C (zh) |
| AT (1) | ATE188966T1 (zh) |
| AU (1) | AU679573B2 (zh) |
| BG (1) | BG62405B1 (zh) |
| BR (1) | BR9407812A (zh) |
| CA (1) | CA2173857A1 (zh) |
| CZ (1) | CZ106996A3 (zh) |
| DE (1) | DE69422724T2 (zh) |
| DK (1) | DK0723546T3 (zh) |
| ES (1) | ES2142413T3 (zh) |
| FI (1) | FI961630A (zh) |
| GB (1) | GB9321162D0 (zh) |
| GR (1) | GR3032480T3 (zh) |
| HU (1) | HUT74580A (zh) |
| IL (1) | IL111259A (zh) |
| IN (1) | IN179169B (zh) |
| MY (1) | MY112110A (zh) |
| NO (1) | NO306509B1 (zh) |
| NZ (1) | NZ274500A (zh) |
| PL (1) | PL177920B1 (zh) |
| PT (1) | PT723546E (zh) |
| RO (1) | RO117020B1 (zh) |
| RU (1) | RU2136684C1 (zh) |
| SK (1) | SK282329B6 (zh) |
| TW (1) | TW372237B (zh) |
| UA (1) | UA42738C2 (zh) |
| WO (1) | WO1995010521A1 (zh) |
| ZA (1) | ZA947949B (zh) |
Families Citing this family (24)
| 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 |
| BR9710729A (pt) | 1996-07-25 | 1999-08-17 | Merck Sharp & Dohme | Composto composi-Æo farmac-utica utiliza-Æo de um composto e processo para o tratamento e/ou a preven-Æo da ansiedade e de convuls{es para a triagem de compostos ansioliticos nÆo-sedativos e para a prepara-Æo de um composto |
| 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 |
| ES2291043T3 (es) * | 1998-10-16 | 2008-02-16 | MERCK SHARP & DOHME LIMITED | Derivados de pirazolotriazina como ligandos para receptores de gaba. |
| GB9906124D0 (en) * | 1999-03-18 | 1999-05-12 | Knoll Ag | Therapeutic agent |
| GB9906130D0 (en) * | 1999-03-18 | 1999-05-12 | Knoll Ag | Compounds for use in therapy |
| GB9906126D0 (en) * | 1999-03-18 | 1999-05-12 | Knoll Ag | Pharmaceutical formulations |
| GB9914743D0 (en) * | 1999-06-24 | 1999-08-25 | Knoll Ag | Therapeutic agents |
| GEP20053688B (en) * | 2000-06-30 | 2005-12-12 | Wyeth Corp | Substituted-Triazolopyrimidines as Anticancer Agents |
| KR100783255B1 (ko) | 2004-02-13 | 2007-12-06 | 워너-램버트 캄파니 엘엘씨 | 안드로젠 수용체 조절제 |
| WO2005100305A1 (en) | 2004-04-13 | 2005-10-27 | Warner-Lambert Company Llc | Androgen modulators |
| WO2005102990A1 (en) | 2004-04-22 | 2005-11-03 | Warner-Lambert Company Llc | Androgen modulators |
| TW200724139A (en) | 2005-05-05 | 2007-07-01 | Warner Lambert Co | Androgen modulators |
| MX2011002278A (es) | 2008-08-29 | 2011-04-14 | Concert Pharmaceuticals Inc | Derivados de triazolo-piridazina sustituidos. |
| DK2414365T3 (da) | 2009-04-01 | 2014-03-31 | Aniona Aps | SUBSTITUEREDE [1,2,4]TRIAZOLO[1,5-a]PYRIMIDINER OG ANVENDELSE HERAF SOM KALIUMKANALMODULATORER |
| WO2010112485A1 (en) | 2009-04-01 | 2010-10-07 | Neurosearch A/S | SUBSTITUTED [1,2,4]TRIAZOLO[1,5-a]PYRIMIDINES AND THEIR USE AS POTASSIUM CHANNEL MODULATORS |
| WO2010112484A1 (en) * | 2009-04-01 | 2010-10-07 | Neurosearch A/S | SUBSTITUTED [1,2,4]TRIAZOLO[1,5-a]PYRIMIDINES AND THEIR USE AS POTASSIUM CHANNEL MODULATORS |
| CA3138307A1 (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 (3)
| 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 |
| 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 CN CN94194265A patent/CN1040537C/zh not_active Expired - Fee Related
- 1994-10-12 AU AU78554/94A patent/AU679573B2/en not_active Ceased
- 1994-10-12 RO RO96-00795A patent/RO117020B1/ro unknown
- 1994-10-12 PT PT94929537T patent/PT723546E/pt unknown
- 1994-10-12 NZ NZ274500A patent/NZ274500A/en unknown
- 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 CA CA002173857A patent/CA2173857A1/en not_active Abandoned
- 1994-10-12 CZ CZ961069A patent/CZ106996A3/cs unknown
- 1994-10-12 ZA ZA947949A patent/ZA947949B/xx unknown
- 1994-10-12 IL IL111259A patent/IL111259A/en not_active IP Right Cessation
- 1994-10-12 BR BR9407812A patent/BR9407812A/pt not_active Application Discontinuation
- 1994-10-12 RU RU96108927A patent/RU2136684C1/ru active
- 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 PL PL94313970A patent/PL177920B1/pl unknown
- 1994-10-12 ES ES94929537T patent/ES2142413T3/es not_active Expired - Lifetime
- 1994-10-12 US US08/628,662 patent/US5753665A/en not_active Expired - Lifetime
- 1994-10-12 JP JP7511287A patent/JPH09503771A/ja not_active Ceased
- 1994-10-12 AT AT94929537T patent/ATE188966T1/de not_active IP Right Cessation
- 1994-10-12 UA UA96041428A patent/UA42738C2/uk unknown
- 1994-10-12 DK DK94929537T patent/DK0723546T3/da active
- 1994-10-12 HU HU9600959A patent/HUT74580A/hu 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/FI961630A/fi unknown
-
2000
- 2000-01-26 GR GR20000400175T patent/GR3032480T3/el not_active IP Right Cessation
Also Published As
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