CZ305099B6 - Derivát pyrazolu, způsoby a meziprodukty pro výrobu, farmaceutická kompozice s jeho obsahem a jeho lékařské aplikace, zejména k léčení infekcí HIV - Google Patents
Derivát pyrazolu, způsoby a meziprodukty pro výrobu, farmaceutická kompozice s jeho obsahem a jeho lékařské aplikace, zejména k léčení infekcí HIV Download PDFInfo
- Publication number
- CZ305099B6 CZ305099B6 CZ2003-2676A CZ20032676A CZ305099B6 CZ 305099 B6 CZ305099 B6 CZ 305099B6 CZ 20032676 A CZ20032676 A CZ 20032676A CZ 305099 B6 CZ305099 B6 CZ 305099B6
- Authority
- CZ
- Czechia
- Prior art keywords
- pyrazol
- methyl
- oxy
- diethyl
- dichlorophenoxy
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 91
- 150000003217 pyrazoles Chemical class 0.000 title claims abstract description 79
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 18
- 230000008569 process Effects 0.000 title claims abstract description 6
- 208000031886 HIV Infections Diseases 0.000 title claims description 9
- 208000037357 HIV infectious disease Diseases 0.000 title claims description 6
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 title claims description 6
- 239000000543 intermediate Substances 0.000 title abstract description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 324
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 69
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 49
- 208000030507 AIDS Diseases 0.000 claims abstract description 18
- 239000001257 hydrogen Substances 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 10
- 241001430294 unidentified retrovirus Species 0.000 claims abstract description 9
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 8
- -1 azetidinyl- Chemical group 0.000 claims description 340
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 122
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 110
- 150000003839 salts Chemical class 0.000 claims description 107
- 239000012453 solvate Substances 0.000 claims description 80
- 229910052757 nitrogen Inorganic materials 0.000 claims description 79
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 66
- 229910052736 halogen Inorganic materials 0.000 claims description 64
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 60
- 229910052799 carbon Inorganic materials 0.000 claims description 59
- 150000002367 halogens Chemical class 0.000 claims description 47
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 43
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 42
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 41
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 35
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- 125000004043 oxo group Chemical group O=* 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 229920006395 saturated elastomer Polymers 0.000 claims description 17
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 150000001721 carbon Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 12
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 12
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical group [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 7
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 6
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 6
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 6
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 6
- NWJRLKOPSVAONP-UHFFFAOYSA-N 4-(3,5-dichlorophenoxy)-3,5-diethyl-1h-pyrazole Chemical compound CCC1=NNC(CC)=C1OC1=CC(Cl)=CC(Cl)=C1 NWJRLKOPSVAONP-UHFFFAOYSA-N 0.000 claims description 5
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 230000002140 halogenating effect Effects 0.000 claims description 5
- LAQPNDIUHRHNCV-UHFFFAOYSA-N isophthalonitrile Chemical compound N#CC1=CC=CC(C#N)=C1 LAQPNDIUHRHNCV-UHFFFAOYSA-N 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 5
- JGOLOOOFWVLWTN-UHFFFAOYSA-N 3-[1-(2-aminoethyl)-3,5-diethylpyrazol-4-yl]oxy-5-methylbenzonitrile Chemical compound CCC1=NN(CCN)C(CC)=C1OC1=CC(C)=CC(C#N)=C1 JGOLOOOFWVLWTN-UHFFFAOYSA-N 0.000 claims description 4
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 4
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 4
- 230000018044 dehydration Effects 0.000 claims description 4
- 238000006297 dehydration reaction Methods 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- 239000010452 phosphate Substances 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
- NYBBRMVVCBSWRG-UHFFFAOYSA-N 1-(azetidin-3-yl)-4-(3,5-dichlorophenoxy)-3,5-diethylpyrazole Chemical compound CCC1=C(OC=2C=C(Cl)C=C(Cl)C=2)C(CC)=NN1C1CNC1 NYBBRMVVCBSWRG-UHFFFAOYSA-N 0.000 claims description 3
- GXZSRCLTCYULLM-UHFFFAOYSA-N 1-[4-(3,5-dichlorophenoxy)-3,5-diethylpyrazol-1-yl]propan-2-ol Chemical compound CCC1=NN(CC(C)O)C(CC)=C1OC1=CC(Cl)=CC(Cl)=C1 GXZSRCLTCYULLM-UHFFFAOYSA-N 0.000 claims description 3
- YIVHNLCDRURFJJ-UHFFFAOYSA-N 2-[2-[4-(3,5-dichlorophenoxy)-3,5-diethylpyrazol-1-yl]ethoxy]ethanamine Chemical compound CCC1=NN(CCOCCN)C(CC)=C1OC1=CC(Cl)=CC(Cl)=C1 YIVHNLCDRURFJJ-UHFFFAOYSA-N 0.000 claims description 3
- NWCGPEVEQLFEQE-UHFFFAOYSA-N 2-[4-(2,5-dichlorophenoxy)-3,5-diethylpyrazol-1-yl]ethanol Chemical compound CCC1=NN(CCO)C(CC)=C1OC1=CC(Cl)=CC=C1Cl NWCGPEVEQLFEQE-UHFFFAOYSA-N 0.000 claims description 3
- LQYBWWAKXOIVBY-UHFFFAOYSA-N 2-[4-(3,5-dichlorophenoxy)-3,5-diethylpyrazol-1-yl]acetonitrile Chemical compound CCC1=NN(CC#N)C(CC)=C1OC1=CC(Cl)=CC(Cl)=C1 LQYBWWAKXOIVBY-UHFFFAOYSA-N 0.000 claims description 3
- WHIHJIHBDBTVEQ-UHFFFAOYSA-N 2-[4-(3,5-dichlorophenoxy)-3,5-diethylpyrazol-1-yl]ethanamine Chemical compound CCC1=NN(CCN)C(CC)=C1OC1=CC(Cl)=CC(Cl)=C1 WHIHJIHBDBTVEQ-UHFFFAOYSA-N 0.000 claims description 3
- PFFCLZRYUXYYMI-UHFFFAOYSA-N 2-[4-(3,5-dichlorophenoxy)-3,5-diethylpyrazol-1-yl]ethanol Chemical compound CCC1=NN(CCO)C(CC)=C1OC1=CC(Cl)=CC(Cl)=C1 PFFCLZRYUXYYMI-UHFFFAOYSA-N 0.000 claims description 3
- UOLIKVWUFHHUHI-UHFFFAOYSA-N 2-[4-(3,5-dichlorophenoxy)-3,5-dimethylpyrazol-1-yl]ethanol Chemical compound CC1=NN(CCO)C(C)=C1OC1=CC(Cl)=CC(Cl)=C1 UOLIKVWUFHHUHI-UHFFFAOYSA-N 0.000 claims description 3
- FBFPCQPPGUKQAK-UHFFFAOYSA-N 2-[4-(3,5-dichlorophenoxy)-3-ethyl-5-methoxypyrazol-1-yl]ethanol Chemical compound CCC1=NN(CCO)C(OC)=C1OC1=CC(Cl)=CC(Cl)=C1 FBFPCQPPGUKQAK-UHFFFAOYSA-N 0.000 claims description 3
- FQQPXUVJYJBXQP-UHFFFAOYSA-N 2-[4-(3,5-dichlorophenoxy)-3-ethylpyrazol-1-yl]ethanamine Chemical compound CCC1=NN(CCN)C=C1OC1=CC(Cl)=CC(Cl)=C1 FQQPXUVJYJBXQP-UHFFFAOYSA-N 0.000 claims description 3
- PIWKXOXFTGYFHS-UHFFFAOYSA-N 2-[4-(3,5-dichlorophenoxy)-5-(ethoxymethyl)-3-ethylpyrazol-1-yl]ethanamine Chemical compound CCC1=NN(CCN)C(COCC)=C1OC1=CC(Cl)=CC(Cl)=C1 PIWKXOXFTGYFHS-UHFFFAOYSA-N 0.000 claims description 3
- GIRIKSBOYGXKJR-UHFFFAOYSA-N 2-[4-[3,5-di(pyrazol-1-yl)phenoxy]-3,5-diethylpyrazol-1-yl]ethanol Chemical compound CCC1=NN(CCO)C(CC)=C1OC1=CC(N2N=CC=C2)=CC(N2N=CC=C2)=C1 GIRIKSBOYGXKJR-UHFFFAOYSA-N 0.000 claims description 3
- VVGYCRUYKAWXDL-UHFFFAOYSA-N 3-(3,5-dichlorophenoxy)-2-ethyl-5-[(4-methoxyphenyl)methyl]-6,7-dihydro-4h-pyrazolo[1,5-a]pyrazine Chemical compound C1C2=C(OC=3C=C(Cl)C=C(Cl)C=3)C(CC)=NN2CCN1CC1=CC=C(OC)C=C1 VVGYCRUYKAWXDL-UHFFFAOYSA-N 0.000 claims description 3
- KYRBQVXJGVZRAC-UHFFFAOYSA-N 3-(3,5-dichlorophenoxy)-2-ethyl-5-methyl-6,7-dihydro-4h-pyrazolo[1,5-a]pyrazine Chemical compound CCC1=NN2CCN(C)CC2=C1OC1=CC(Cl)=CC(Cl)=C1 KYRBQVXJGVZRAC-UHFFFAOYSA-N 0.000 claims description 3
- KKJHEPWZHIDPCT-UHFFFAOYSA-N 3-(3,5-diethyl-1-methylpyrazol-4-yl)oxybenzonitrile Chemical compound CCC1=NN(C)C(CC)=C1OC1=CC=CC(C#N)=C1 KKJHEPWZHIDPCT-UHFFFAOYSA-N 0.000 claims description 3
- ZBLUZFKVPAMTKM-UHFFFAOYSA-N 3-[1-(2-aminoethyl)-3-cyclopropyl-5-methylpyrazol-4-yl]oxy-5-methylbenzonitrile Chemical compound C1CC1C1=NN(CCN)C(C)=C1OC1=CC(C)=CC(C#N)=C1 ZBLUZFKVPAMTKM-UHFFFAOYSA-N 0.000 claims description 3
- XOUBIEGVHRLPGQ-UHFFFAOYSA-N 3-[1-(3-aminopropyl)-3,5-diethylpyrazol-4-yl]oxy-5-methylbenzonitrile Chemical compound CCC1=NN(CCCN)C(CC)=C1OC1=CC(C)=CC(C#N)=C1 XOUBIEGVHRLPGQ-UHFFFAOYSA-N 0.000 claims description 3
- RMHAAZPQTJAEDU-UHFFFAOYSA-N 3-[3,5-diethyl-1-(2-hydroxyethyl)pyrazol-4-yl]oxy-4-methoxybenzonitrile Chemical compound CCC1=NN(CCO)C(CC)=C1OC1=CC(C#N)=CC=C1OC RMHAAZPQTJAEDU-UHFFFAOYSA-N 0.000 claims description 3
- GBCRCJDZIRWODT-UHFFFAOYSA-N 3-[3,5-diethyl-1-(2-hydroxyethyl)pyrazol-4-yl]oxy-5-fluorobenzamide Chemical compound CCC1=NN(CCO)C(CC)=C1OC1=CC(F)=CC(C(N)=O)=C1 GBCRCJDZIRWODT-UHFFFAOYSA-N 0.000 claims description 3
- SVTFKLREEGKUHR-UHFFFAOYSA-N 3-[3,5-diethyl-1-(2-hydroxyethyl)pyrazol-4-yl]oxy-5-fluorobenzonitrile Chemical compound CCC1=NN(CCO)C(CC)=C1OC1=CC(F)=CC(C#N)=C1 SVTFKLREEGKUHR-UHFFFAOYSA-N 0.000 claims description 3
- HYGAQDKRJPFEDE-UHFFFAOYSA-N 3-[3,5-diethyl-1-(2-hydroxyethyl)pyrazol-4-yl]oxy-5-methoxybenzonitrile Chemical compound CCC1=NN(CCO)C(CC)=C1OC1=CC(OC)=CC(C#N)=C1 HYGAQDKRJPFEDE-UHFFFAOYSA-N 0.000 claims description 3
- UUJFOHNJISSDEY-UHFFFAOYSA-N 3-[5-(aminomethyl)-1-(2-hydroxyethyl)-3-methylpyrazol-4-yl]oxy-5-chlorobenzonitrile Chemical compound CC1=NN(CCO)C(CN)=C1OC1=CC(Cl)=CC(C#N)=C1 UUJFOHNJISSDEY-UHFFFAOYSA-N 0.000 claims description 3
- AOEIDJLLHYAKNQ-UHFFFAOYSA-N 3-[5-(bromomethyl)-1,3-dimethylpyrazol-4-yl]oxy-5-chlorobenzonitrile Chemical compound CC1=NN(C)C(CBr)=C1OC1=CC(Cl)=CC(C#N)=C1 AOEIDJLLHYAKNQ-UHFFFAOYSA-N 0.000 claims description 3
- GGESYNCXMNSGOM-UHFFFAOYSA-N 3-[5-cyclopropyl-1-(2-hydroxyethyl)-3-methylpyrazol-4-yl]oxy-5-methylbenzonitrile Chemical compound C=1C(C)=CC(C#N)=CC=1OC=1C(C)=NN(CCO)C=1C1CC1 GGESYNCXMNSGOM-UHFFFAOYSA-N 0.000 claims description 3
- TZELNKSFAMXOLI-UHFFFAOYSA-N 3-[[3-ethyl-5-(2-hydroxyethyl)-1h-pyrazol-4-yl]oxy]-5-fluorobenzonitrile Chemical compound CCC1=NNC(CCO)=C1OC1=CC(F)=CC(C#N)=C1 TZELNKSFAMXOLI-UHFFFAOYSA-N 0.000 claims description 3
- BONXULVQGQKWMP-UHFFFAOYSA-N 3-[[3-ethyl-5-(2-phenylmethoxyethyl)-1h-pyrazol-4-yl]oxy]-5-fluorobenzonitrile Chemical compound C=1C(F)=CC(C#N)=CC=1OC=1C(CC)=NNC=1CCOCC1=CC=CC=C1 BONXULVQGQKWMP-UHFFFAOYSA-N 0.000 claims description 3
- JEHLYPYZNUNCOU-UHFFFAOYSA-N 3-[[4-(3,5-dichlorophenoxy)-3,5-diethylpyrazol-1-yl]methyl]-2h-1,2,4-oxadiazol-5-one Chemical compound CCC1=C(OC=2C=C(Cl)C=C(Cl)C=2)C(CC)=NN1CC1=NOC(O)=N1 JEHLYPYZNUNCOU-UHFFFAOYSA-N 0.000 claims description 3
- ZYJBTKANMLSSQC-UHFFFAOYSA-N 3-[[4-(3,5-dichlorophenoxy)-3,5-diethylpyrazol-1-yl]methyl]morpholine Chemical compound CCC1=C(OC=2C=C(Cl)C=C(Cl)C=2)C(CC)=NN1CC1COCCN1 ZYJBTKANMLSSQC-UHFFFAOYSA-N 0.000 claims description 3
- KBXLTNCYZRLYRX-UHFFFAOYSA-N 3-[[5-[2-(4-cyanophenoxy)ethyl]-3-ethyl-1h-pyrazol-4-yl]oxy]-5-fluorobenzonitrile Chemical compound C=1C(F)=CC(C#N)=CC=1OC=1C(CC)=NNC=1CCOC1=CC=C(C#N)C=C1 KBXLTNCYZRLYRX-UHFFFAOYSA-N 0.000 claims description 3
- PBWXQLFVQNUMIG-UHFFFAOYSA-N 3-chloro-5-[(3,5-dimethyl-1h-pyrazol-4-yl)oxy]benzonitrile Chemical compound CC1=NNC(C)=C1OC1=CC(Cl)=CC(C#N)=C1 PBWXQLFVQNUMIG-UHFFFAOYSA-N 0.000 claims description 3
- VCXAEFPBASGKCZ-UHFFFAOYSA-N 3-chloro-5-[1-(2-hydroxyethyl)-3,5-dimethylpyrazol-4-yl]oxybenzonitrile Chemical compound CC1=NN(CCO)C(C)=C1OC1=CC(Cl)=CC(C#N)=C1 VCXAEFPBASGKCZ-UHFFFAOYSA-N 0.000 claims description 3
- DKGMPXBTZVBXHV-UHFFFAOYSA-N 3-chloro-5-[5-[[(4-cyanophenyl)methylamino]methyl]-1-(2-hydroxyethyl)-3-methylpyrazol-4-yl]oxybenzonitrile Chemical compound C=1C(Cl)=CC(C#N)=CC=1OC=1C(C)=NN(CCO)C=1CNCC1=CC=C(C#N)C=C1 DKGMPXBTZVBXHV-UHFFFAOYSA-N 0.000 claims description 3
- WYKYIZNMDJQGBI-UHFFFAOYSA-N 3-chloro-5-[[3-[[(4-cyanophenyl)methylamino]methyl]-5-methyl-1h-pyrazol-4-yl]oxy]benzonitrile Chemical compound C=1C(Cl)=CC(C#N)=CC=1OC=1C(C)=NNC=1CNCC1=CC=C(C#N)C=C1 WYKYIZNMDJQGBI-UHFFFAOYSA-N 0.000 claims description 3
- KYJYHDRXBIBZGG-UHFFFAOYSA-N 3-chloro-5-[[5-methyl-3-(piperazin-1-ylmethyl)-1h-pyrazol-4-yl]oxy]benzonitrile Chemical compound C=1C(Cl)=CC(C#N)=CC=1OC=1C(C)=NNC=1CN1CCNCC1 KYJYHDRXBIBZGG-UHFFFAOYSA-N 0.000 claims description 3
- PPXRXRKOAQYRDV-UHFFFAOYSA-N 3-chloro-5-[[5-methyl-3-[(2-methylimidazol-1-yl)methyl]-1h-pyrazol-4-yl]oxy]benzonitrile Chemical compound C=1C(Cl)=CC(C#N)=CC=1OC=1C(C)=NNC=1CN1C=CN=C1C PPXRXRKOAQYRDV-UHFFFAOYSA-N 0.000 claims description 3
- RKXTZYDNSDGOLF-UHFFFAOYSA-N 3-chloro-5-[[5-methyl-3-[(4-methylsulfonylpiperazin-1-yl)methyl]-1h-pyrazol-4-yl]oxy]benzonitrile Chemical compound C=1C(Cl)=CC(C#N)=CC=1OC=1C(C)=NNC=1CN1CCN(S(C)(=O)=O)CC1 RKXTZYDNSDGOLF-UHFFFAOYSA-N 0.000 claims description 3
- UHWFOCVNHNAMDM-UHFFFAOYSA-N 3-tert-butyl-4-(3,5-dichlorophenoxy)-5-methyl-1h-pyrazole Chemical compound N1N=C(C(C)(C)C)C(OC=2C=C(Cl)C=C(Cl)C=2)=C1C UHWFOCVNHNAMDM-UHFFFAOYSA-N 0.000 claims description 3
- PQYMPFONJYEFTE-UHFFFAOYSA-N 4-(3,5-dichlorophenoxy)-3,5-diethyl-1-(1-methylazetidin-3-yl)pyrazole Chemical compound CCC1=C(OC=2C=C(Cl)C=C(Cl)C=2)C(CC)=NN1C1CN(C)C1 PQYMPFONJYEFTE-UHFFFAOYSA-N 0.000 claims description 3
- YRSNNEIJPUFZNE-UHFFFAOYSA-N 4-(3,5-dichlorophenoxy)-3,5-diethyl-1-(2-methoxyethyl)pyrazole Chemical compound CCC1=NN(CCOC)C(CC)=C1OC1=CC(Cl)=CC(Cl)=C1 YRSNNEIJPUFZNE-UHFFFAOYSA-N 0.000 claims description 3
- MDUVBKHILSDHGL-UHFFFAOYSA-N 4-(3,5-dichlorophenoxy)-3,5-dimethyl-1h-pyrazole Chemical compound CC1=NNC(C)=C1OC1=CC(Cl)=CC(Cl)=C1 MDUVBKHILSDHGL-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/18—One oxygen or sulfur atom
- C07D231/20—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
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Applications Claiming Priority (2)
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| GB0108999A GB0108999D0 (en) | 2001-04-10 | 2001-04-10 | Pyrazole derivatives |
| GB0127426A GB0127426D0 (en) | 2001-11-15 | 2001-11-15 | Pyrazole derivatives |
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| CZ20032676A3 CZ20032676A3 (cs) | 2004-11-10 |
| CZ305099B6 true CZ305099B6 (cs) | 2015-05-06 |
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| CZ2003-2676A CZ305099B6 (cs) | 2001-04-10 | 2002-04-04 | Derivát pyrazolu, způsoby a meziprodukty pro výrobu, farmaceutická kompozice s jeho obsahem a jeho lékařské aplikace, zejména k léčení infekcí HIV |
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