RU2059636C1 - Оксазолильные производные или их фармацевтически приемлемая аддитивная соль, или их стереохимически изомерная форма, способ их получения и фармацевтическая композиция, обладающая антиаллергической активностью - Google Patents
Оксазолильные производные или их фармацевтически приемлемая аддитивная соль, или их стереохимически изомерная форма, способ их получения и фармацевтическая композиция, обладающая антиаллергической активностью Download PDFInfo
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- RU2059636C1 RU2059636C1 RU9192016607A RU92016607A RU2059636C1 RU 2059636 C1 RU2059636 C1 RU 2059636C1 RU 9192016607 A RU9192016607 A RU 9192016607A RU 92016607 A RU92016607 A RU 92016607A RU 2059636 C1 RU2059636 C1 RU 2059636C1
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- Russia
- Prior art keywords
- methyl
- alkyl
- parts
- formula
- hydrogen
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- 150000003839 salts Chemical class 0.000 title claims abstract description 40
- 238000000034 method Methods 0.000 title claims abstract description 30
- 230000003266 anti-allergic effect Effects 0.000 title claims abstract description 12
- 239000000654 additive Substances 0.000 title claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 230000000996 additive effect Effects 0.000 title claims 2
- 230000015572 biosynthetic process Effects 0.000 title abstract description 6
- 238000003786 synthesis reaction Methods 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 162
- 239000012442 inert solvent Substances 0.000 claims abstract description 8
- 150000001350 alkyl halides Chemical class 0.000 claims abstract description 3
- 229910044991 metal oxide Inorganic materials 0.000 claims abstract description 3
- 150000004706 metal oxides Chemical class 0.000 claims abstract description 3
- 239000002184 metal Chemical class 0.000 claims abstract 2
- -1 3-phenylpropenyl Chemical group 0.000 claims description 216
- 239000001257 hydrogen Substances 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 62
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 46
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 125000004076 pyridyl group Chemical group 0.000 claims description 21
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 6
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 4
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims 3
- 125000006401 halopyridazinyl group Chemical group 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 claims 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 101
- 230000000694 effects Effects 0.000 abstract description 4
- 238000007363 ring formation reaction Methods 0.000 abstract description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 100
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 78
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 70
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- 239000011541 reaction mixture Substances 0.000 description 49
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- 150000003254 radicals Chemical class 0.000 description 47
- 239000000243 solution Substances 0.000 description 46
- 238000006243 chemical reaction Methods 0.000 description 41
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
- 239000000543 intermediate Substances 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000000741 silica gel Substances 0.000 description 32
- 229910002027 silica gel Inorganic materials 0.000 description 32
- 238000004440 column chromatography Methods 0.000 description 31
- 239000003480 eluent Substances 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- 239000000460 chlorine Substances 0.000 description 30
- 239000000047 product Substances 0.000 description 29
- 125000003118 aryl group Chemical group 0.000 description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 25
- 238000003756 stirring Methods 0.000 description 25
- 229960004592 isopropanol Drugs 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 19
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 18
- 238000001816 cooling Methods 0.000 description 17
- 238000004821 distillation Methods 0.000 description 17
- 239000012044 organic layer Substances 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 12
- 239000000284 extract Substances 0.000 description 12
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 11
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 11
- 229910052757 nitrogen Chemical group 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 9
- 238000007126 N-alkylation reaction Methods 0.000 description 9
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 9
- 229960001701 chloroform Drugs 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- 239000011593 sulfur Chemical group 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 7
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 150000002576 ketones Chemical class 0.000 description 7
- 239000003880 polar aprotic solvent Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 125000004093 cyano group Chemical group *C#N 0.000 description 6
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- 229930192474 thiophene Natural products 0.000 description 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 5
- QNWXXDZUTFZYRH-UHFFFAOYSA-N 5-(bromomethyl)-2-methyl-1,3-oxazole Chemical compound CC1=NC=C(CBr)O1 QNWXXDZUTFZYRH-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 150000008282 halocarbons Chemical class 0.000 description 5
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(II) oxide Inorganic materials [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 239000003245 coal Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 3
- UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004342 Benzoyl peroxide Substances 0.000 description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 0 CCC(C)C(CCC1(*I)C(C)C1)(*N)O Chemical compound CCC(C)C(CCC1(*I)C(C)C1)(*N)O 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 229910001516 alkali metal iodide Inorganic materials 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000000043 antiallergic agent Substances 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 150000002540 isothiocyanates Chemical class 0.000 description 3
- 231100000225 lethality Toxicity 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- MSTNCTVIENDXHQ-UHFFFAOYSA-N (1-methylpiperidin-4-yl)thiourea Chemical compound CN1CCC(NC(N)=S)CC1 MSTNCTVIENDXHQ-UHFFFAOYSA-N 0.000 description 2
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55432690A | 1990-07-19 | 1990-07-19 | |
| US554326 | 1990-07-19 | ||
| PCT/EP1991/001291 WO1992001687A1 (en) | 1990-07-19 | 1991-07-09 | Novel oxazolyl derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU92016607A RU92016607A (ru) | 1995-06-19 |
| RU2059636C1 true RU2059636C1 (ru) | 1996-05-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU9192016607A RU2059636C1 (ru) | 1990-07-19 | 1991-07-09 | Оксазолильные производные или их фармацевтически приемлемая аддитивная соль, или их стереохимически изомерная форма, способ их получения и фармацевтическая композиция, обладающая антиаллергической активностью |
Country Status (31)
| Country | Link |
|---|---|
| EP (1) | EP0539421B1 (enExample) |
| JP (1) | JP3070951B2 (enExample) |
| KR (1) | KR100190299B1 (enExample) |
| CN (1) | CN1043640C (enExample) |
| AP (1) | AP267A (enExample) |
| AT (1) | ATE171449T1 (enExample) |
| AU (1) | AU644202B2 (enExample) |
| BG (1) | BG61342B1 (enExample) |
| CA (1) | CA2086545A1 (enExample) |
| CZ (1) | CZ279344B6 (enExample) |
| DE (1) | DE69130255T2 (enExample) |
| ES (1) | ES2121784T3 (enExample) |
| FI (1) | FI930198A0 (enExample) |
| HU (1) | HUT64340A (enExample) |
| IE (1) | IE912532A1 (enExample) |
| IL (1) | IL98864A (enExample) |
| MA (1) | MA22226A1 (enExample) |
| MX (1) | MX9100312A (enExample) |
| MY (1) | MY107973A (enExample) |
| NO (1) | NO300459B1 (enExample) |
| NZ (1) | NZ238864A (enExample) |
| PL (1) | PL169361B1 (enExample) |
| PT (1) | PT98365B (enExample) |
| RO (1) | RO111768B1 (enExample) |
| RU (1) | RU2059636C1 (enExample) |
| SK (1) | SK278133B6 (enExample) |
| TN (1) | TNSN91062A1 (enExample) |
| TW (1) | TW235964B (enExample) |
| WO (1) | WO1992001687A1 (enExample) |
| YU (1) | YU126391A (enExample) |
| ZA (1) | ZA915653B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2346944C2 (ru) * | 2003-05-19 | 2009-02-20 | Санофи-Авентис Дойчланд Гмбх | ПРОИЗВОДНЫЕ БЕНЗИМИДАЗОЛА В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА Ха |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW222274B (enExample) * | 1992-01-09 | 1994-04-11 | Janssen Pharmaceutica Nv | |
| US6211199B1 (en) | 1995-11-17 | 2001-04-03 | Aventis Pharmaceuticals Inc. | Substituted 4-(1H-benzimidazol-2-yl-amino)piperidines useful for the treatment of allergic diseases |
| US6194406B1 (en) | 1995-12-20 | 2001-02-27 | Aventis Pharmaceuticals Inc. | Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic disease |
| US6423704B2 (en) | 1995-12-20 | 2002-07-23 | Aventis Pharmaceuticals Inc. | Substituted 4-(1H-benzimidazol-2-yl)[1,4]diazepanes useful for the treatment of allergic diseases |
| US5932571A (en) * | 1996-02-21 | 1999-08-03 | Hoechst Marion Roussel, Inc. | Substituted N-methyl-N-(4-(4-(1H-benzimidazol-2-yl) {1,4}diazepan-1-yl)-2-(aryl) butyl) benzamides useful for the treatment of allergic diseases |
| US5922737A (en) * | 1996-02-21 | 1999-07-13 | Hoechst Marion Roussel, Inc. | Substituted N-methyl-N-(4-(4-(1H-Benzimidazol-2-YL-amino) piperidin-1-YL)-2-(arlyl) butyl) benzamides useful for the treatment of allergic diseases |
| US5998439A (en) | 1996-02-21 | 1999-12-07 | Hoescht Marion Roussel, Inc. | Substituted N-methyl-N-(4-(piperidin-1-yl)-2-(aryl)butyl)benzamides useful for the treatment of allergic diseases |
| ATE258928T1 (de) | 1999-06-28 | 2004-02-15 | Janssen Pharmaceutica Nv | Respiratorisches syncytialvirus replikation inhibitoren |
| HUP0201789A3 (en) | 1999-06-28 | 2003-12-29 | Janssen Pharmaceutica Nv | Respiratory syncytial virus replication inhibitors |
| EP1196408B1 (en) | 1999-06-28 | 2004-09-15 | Janssen Pharmaceutica N.V. | Respiratory syncytial virus replication inhibitors |
| GB0315203D0 (en) * | 2003-06-28 | 2003-08-06 | Celltech R&D Ltd | Chemical compounds |
| AR046971A1 (es) | 2003-12-18 | 2006-01-04 | Tibotec Pharm Ltd | Aminobenzoimidazoles y benzoimidazoles como inhibidores de la replicacion del virus sincitial respiratorio |
| US7355051B2 (en) | 2003-12-18 | 2008-04-08 | Tibotec Pharmaceuticals | Piperdine-amino-benzimidazole derivatives as inhibitors of respiratory syncytial virus replication |
| RU2369606C2 (ru) | 2003-12-18 | 2009-10-10 | Тиботек Фармасьютикалз Лтд. | Производные 5- или 6-замещенных бензимидазолов в качестве ингибиторов репликации респираторного синцитиального вируса |
| US7855194B2 (en) | 2006-03-27 | 2010-12-21 | Hoffmann-La Roche Inc. | Pyrimidine, quinazoline, pteridine and triazine derivatives |
| TWI377511B (en) | 2008-12-05 | 2012-11-21 | Ind Tech Res Inst | Flame detecting method and system |
| RU2417995C1 (ru) * | 2009-09-21 | 2011-05-10 | Государственное образовательное учреждение высшего профессионального образования "Кубанский государственный технологический университет" (ГОУ ВПО "КубГТУ") | Способ получения 3-(2-замещенных-1,3-оксазол-4-ил)пиридин-2(1н)-онов |
| CN104098609B (zh) * | 2014-07-28 | 2016-08-17 | 陕西科技大学 | 含二茂铁的咪唑并[2,1-b]-1,3,4-噻二唑、制备方法及其应用 |
| US10752588B2 (en) | 2014-12-19 | 2020-08-25 | The Broad Institute, Inc. | Dopamine D2 receptor ligands |
| US10633336B2 (en) | 2014-12-19 | 2020-04-28 | The Broad Institute, Inc. | Dopamine D2 receptor ligands |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4556660A (en) * | 1982-07-12 | 1985-12-03 | Janssen Pharmaceutica N.V. | N-(Bicyclic heterocyclyl)-4-piperidinamines |
| US4634704A (en) * | 1983-10-06 | 1987-01-06 | Janssen Pharmaceutica, N.V. | Anti-allergic five membered heterocyclic ring containing N-(bicyclic heterocycyl)-4-piperidinamines |
| US4695569A (en) * | 1983-11-30 | 1987-09-22 | Janssen Pharmaceutica N.V. | Bicyclic heterocyclyl containing N-(bicyclic heterocyclyl)-4-piperidinamines |
| PH23995A (en) * | 1984-01-09 | 1990-02-09 | Janssen Pharmaceutica Nv | 4((bicycle heterocyclyl)-methyl and hetero)piperidines |
| US4588722A (en) * | 1984-01-09 | 1986-05-13 | Janssen Pharmaceutica N.V. | N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives |
| KR930005004B1 (ko) * | 1985-04-15 | 1993-06-11 | 쟈안센 파아마슈우티카 엔. 부이. | 치환된 n-[(4-피페리디닐)알킬]이환 축합 옥사졸아민 및 티아졸아민의 제조방법 |
| GB8515934D0 (en) * | 1985-06-24 | 1985-07-24 | Janssen Pharmaceutica Nv | (4-piperidinomethyl and-hetero)purines |
| US4835161A (en) * | 1986-02-03 | 1989-05-30 | Janssen Pharmaceutica N.V. | Anti-histaminic compositions containing n-heterocyclyl-4-piperidinamines |
| US4897401A (en) * | 1987-06-19 | 1990-01-30 | Janssen Pharmaceutical N.V. | N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives useful in treating allergic diseases |
| CA1317939C (en) * | 1987-07-01 | 1993-05-18 | Janssen Pharmaceutica Naamloze Vennootschap | ¬(bicyclic heterocyclyl)methyl and -hetero| substituted hexahydro-1h-azepines and pyrrolidines |
-
1990
- 1990-07-19 KR KR1019930700123A patent/KR100190299B1/ko not_active Expired - Fee Related
-
1991
- 1991-07-05 NZ NZ238864A patent/NZ238864A/xx unknown
- 1991-07-09 AU AU82141/91A patent/AU644202B2/en not_active Ceased
- 1991-07-09 RO RO93-00046A patent/RO111768B1/ro unknown
- 1991-07-09 HU HU9300097A patent/HUT64340A/hu active IP Right Revival
- 1991-07-09 PL PL91297611A patent/PL169361B1/pl unknown
- 1991-07-09 DE DE69130255T patent/DE69130255T2/de not_active Expired - Lifetime
- 1991-07-09 JP JP3511644A patent/JP3070951B2/ja not_active Expired - Lifetime
- 1991-07-09 AT AT91912700T patent/ATE171449T1/de not_active IP Right Cessation
- 1991-07-09 RU RU9192016607A patent/RU2059636C1/ru active
- 1991-07-09 ES ES91912700T patent/ES2121784T3/es not_active Expired - Lifetime
- 1991-07-09 EP EP91912700A patent/EP0539421B1/en not_active Expired - Lifetime
- 1991-07-09 CA CA002086545A patent/CA2086545A1/en not_active Abandoned
- 1991-07-09 WO PCT/EP1991/001291 patent/WO1992001687A1/en not_active Ceased
- 1991-07-16 MA MA22501A patent/MA22226A1/fr unknown
- 1991-07-17 IL IL9886491A patent/IL98864A/en active IP Right Grant
- 1991-07-17 YU YU126391A patent/YU126391A/sh unknown
- 1991-07-18 CZ CS912240A patent/CZ279344B6/cs unknown
- 1991-07-18 AP APAP/P/1991/000298A patent/AP267A/en active
- 1991-07-18 ZA ZA915653A patent/ZA915653B/xx unknown
- 1991-07-18 SK SK2240-91A patent/SK278133B6/sk unknown
- 1991-07-18 MY MYPI91001296A patent/MY107973A/en unknown
- 1991-07-18 PT PT98365A patent/PT98365B/pt not_active IP Right Cessation
- 1991-07-18 IE IE253291A patent/IE912532A1/en unknown
- 1991-07-19 MX MX9100312A patent/MX9100312A/es not_active IP Right Cessation
- 1991-07-19 CN CN91104902A patent/CN1043640C/zh not_active Expired - Fee Related
- 1991-07-19 TN TNTNSN91062A patent/TNSN91062A1/fr unknown
- 1991-07-27 TW TW080105850A patent/TW235964B/zh active
-
1993
- 1993-01-15 BG BG97314A patent/BG61342B1/bg unknown
- 1993-01-18 FI FI930198A patent/FI930198A0/fi not_active Application Discontinuation
- 1993-01-18 NO NO930156A patent/NO300459B1/no unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2346944C2 (ru) * | 2003-05-19 | 2009-02-20 | Санофи-Авентис Дойчланд Гмбх | ПРОИЗВОДНЫЕ БЕНЗИМИДАЗОЛА В КАЧЕСТВЕ ИНГИБИТОРОВ ФАКТОРА Ха |
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