HRP950446A2 - Substituted quinoline derivatives, process for their preparation and their use - Google Patents
Substituted quinoline derivatives, process for their preparation and their use Download PDFInfo
- Publication number
- HRP950446A2 HRP950446A2 HRP4428932.4A HRP950446A HRP950446A2 HR P950446 A2 HRP950446 A2 HR P950446A2 HR P950446 A HRP950446 A HR P950446A HR P950446 A2 HRP950446 A2 HR P950446A2
- Authority
- HR
- Croatia
- Prior art keywords
- fluorine
- chlorine
- hydroxyl
- optionally substituted
- alkoxyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title description 7
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title description 3
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title description 2
- -1 trifluoromethoxyl Chemical group 0.000 claims description 623
- 239000011737 fluorine Substances 0.000 claims description 364
- 229910052731 fluorine Inorganic materials 0.000 claims description 364
- 239000000460 chlorine Substances 0.000 claims description 362
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 360
- 229910052801 chlorine Inorganic materials 0.000 claims description 360
- 125000001153 fluoro group Chemical group F* 0.000 claims description 344
- 125000003545 alkoxy group Chemical group 0.000 claims description 248
- 125000004043 oxo group Chemical group O=* 0.000 claims description 240
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 206
- KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical group O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 claims description 178
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 175
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 148
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 138
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 130
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 130
- 229910052794 bromium Inorganic materials 0.000 claims description 130
- 125000004414 alkyl thio group Chemical group 0.000 claims description 120
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 114
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 112
- 125000005265 dialkylamine group Chemical group 0.000 claims description 108
- 125000004423 acyloxy group Chemical group 0.000 claims description 106
- 150000003973 alkyl amines Chemical class 0.000 claims description 104
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 92
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 85
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical group NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 72
- 150000001412 amines Chemical group 0.000 claims description 71
- 150000001875 compounds Chemical class 0.000 claims description 69
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 56
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 51
- 125000001072 heteroaryl group Chemical group 0.000 claims description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 44
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 43
- 125000005110 aryl thio group Chemical group 0.000 claims description 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 34
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 30
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 29
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 29
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 27
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 27
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 125000003107 substituted aryl group Chemical group 0.000 claims description 25
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 24
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 239000001301 oxygen Substances 0.000 claims description 24
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 23
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 21
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 20
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 20
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 20
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 20
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 150000003254 radicals Chemical class 0.000 claims description 19
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 18
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 18
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 16
- 125000001769 aryl amino group Chemical group 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 239000011593 sulfur Substances 0.000 claims description 15
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 14
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 12
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 12
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 12
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 12
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 12
- 150000002829 nitrogen Chemical class 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 10
- 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 10
- 125000005225 alkynyloxycarbonyl group Chemical group 0.000 claims description 10
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 8
- UUSXWCYNGPPVEF-UHFFFAOYSA-N iodocyanamide Chemical group INC#N UUSXWCYNGPPVEF-UHFFFAOYSA-N 0.000 claims description 8
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 125000002346 iodo group Chemical group I* 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 229910052711 selenium Inorganic materials 0.000 claims description 6
- 239000011669 selenium Substances 0.000 claims description 6
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 5
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 claims description 4
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000004442 acylamino group Chemical group 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- 238000005987 sulfurization reaction Methods 0.000 claims description 4
- 230000003612 virological effect Effects 0.000 claims description 4
- 125000006823 (C1-C6) acyl group Chemical group 0.000 claims description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical group 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 125000005139 alkynylsulfonyl group Chemical group 0.000 claims description 2
- 150000005840 aryl radicals Chemical class 0.000 claims description 2
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 239000012442 inert solvent Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 125000002130 sulfonic acid ester group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 41
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000002904 solvent Substances 0.000 description 30
- 239000000243 solution Substances 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 22
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 20
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- 239000012071 phase Substances 0.000 description 15
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 241000725303 Human immunodeficiency virus Species 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000007795 chemical reaction product Substances 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 150000002431 hydrogen Chemical class 0.000 description 8
- LKNMNWVEDIDQDL-UHFFFAOYSA-N 6-methoxy-3,3-dimethyl-1h-quinoline-2,4-dione Chemical compound N1C(=O)C(C)(C)C(=O)C2=CC(OC)=CC=C21 LKNMNWVEDIDQDL-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- VIRUDUKWDKFQFU-UHFFFAOYSA-N 4-butyl-6-chloro-4-hydroxy-1,3-dihydroquinolin-2-one Chemical compound C1=C(Cl)C=C2C(CCCC)(O)CC(=O)NC2=C1 VIRUDUKWDKFQFU-UHFFFAOYSA-N 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 5
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- 230000000840 anti-viral effect Effects 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
- MBHVGXXZPVRJRC-UHFFFAOYSA-N 4-butyl-4-hydroxy-6-methoxy-3,3-dimethyl-1h-quinolin-2-one Chemical compound COC1=CC=C2NC(=O)C(C)(C)C(CCCC)(O)C2=C1 MBHVGXXZPVRJRC-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
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- 239000012507 Sephadex™ Substances 0.000 description 4
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- 238000001816 cooling Methods 0.000 description 4
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- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 description 3
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 102100034343 Integrase Human genes 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
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- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
- 241000700605 Viruses Species 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- WDAXFOBOLVPGLV-UHFFFAOYSA-N ethyl isobutyrate Chemical compound CCOC(=O)C(C)C WDAXFOBOLVPGLV-UHFFFAOYSA-N 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000002821 scintillation proximity assay Methods 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- GCMNJUJAKQGROZ-UHFFFAOYSA-N 1,2-Dihydroquinolin-2-imine Chemical class C1=CC=CC2=NC(N)=CC=C21 GCMNJUJAKQGROZ-UHFFFAOYSA-N 0.000 description 2
- QSSXUTBSWSYAQP-UHFFFAOYSA-N 6-chloro-3,3-dimethyl-1h-quinoline-2,4-dione Chemical compound C1=C(Cl)C=C2C(=O)C(C)(C)C(=O)NC2=C1 QSSXUTBSWSYAQP-UHFFFAOYSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/36—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Cosmetics (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4428932A DE4428932A1 (de) | 1994-08-16 | 1994-08-16 | Substituierte-Chinolinderivate, Verfahren zu ihrer Herstellung und ihre Verwendung |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP950446A2 true HRP950446A2 (en) | 1997-08-31 |
Family
ID=6525747
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HRP4428932.4A HRP950446A2 (en) | 1994-08-16 | 1995-08-10 | Substituted quinoline derivatives, process for their preparation and their use |
Country Status (24)
Country | Link |
---|---|
US (1) | US5798365A (xx) |
EP (1) | EP0697405B1 (xx) |
JP (1) | JP3860618B2 (xx) |
KR (1) | KR960007567A (xx) |
CN (1) | CN1123275A (xx) |
AT (1) | ATE222239T1 (xx) |
AU (1) | AU710238B2 (xx) |
CA (1) | CA2156128A1 (xx) |
CZ (1) | CZ209095A3 (xx) |
DE (2) | DE4428932A1 (xx) |
DK (1) | DK0697405T3 (xx) |
ES (1) | ES2179857T3 (xx) |
FI (1) | FI953841A (xx) |
HR (1) | HRP950446A2 (xx) |
HU (1) | HUT73133A (xx) |
IL (1) | IL114937A0 (xx) |
NO (1) | NO306296B1 (xx) |
NZ (1) | NZ272730A (xx) |
PL (1) | PL310030A1 (xx) |
PT (1) | PT697405E (xx) |
SI (1) | SI9500260A (xx) |
SK (1) | SK100695A3 (xx) |
TW (1) | TW407151B (xx) |
ZA (1) | ZA956798B (xx) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7397363B2 (en) * | 1993-06-08 | 2008-07-08 | Raymond Anthony Joao | Control and/or monitoring apparatus and method |
US6658833B2 (en) * | 2000-11-09 | 2003-12-09 | Bestrake, Llc | Collector and separator apparatus for lawn and garden |
AU2005316739A1 (en) * | 2004-12-13 | 2006-06-22 | Galileo Pharmaceuticals, Inc. | Spiro derivatives as lipoxygenase inhibitors |
DE102008022221A1 (de) * | 2008-05-06 | 2009-11-12 | Universität des Saarlandes | Inhibitoren der humanen Aldosteronsynthase CYP11B2 |
MA34397B1 (fr) | 2010-07-02 | 2013-07-03 | Gilead Sciences Inc | Dérivés d'acide napht-2-ylacétique dans le traitement du sida |
PE20130525A1 (es) * | 2010-07-02 | 2013-05-05 | Gilead Sciences Inc | Derivados de acido 2 quinolinil acetico como compuestos antivirales frente a vih |
CA2833377C (en) | 2011-04-21 | 2019-02-12 | Gilead Sciences, Inc. | Benzothiazole compounds and their pharmaceutical use |
US9284323B2 (en) | 2012-01-04 | 2016-03-15 | Gilead Sciences, Inc. | Naphthalene acetic acid derivatives against HIV infection |
US9376392B2 (en) | 2012-01-04 | 2016-06-28 | Gilead Sciences, Inc. | 2-(tert-butoxy)-2-(7-methylquinolin-6-yl) acetic acid derivatives for treating AIDS |
PE20141558A1 (es) | 2012-04-20 | 2014-11-06 | Gilead Sciences Inc | Derivados de acido benzotiazol-6-il acetico y su uso para tratar una infeccion por vih |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU1580492A (en) * | 1991-03-14 | 1992-10-21 | Upjohn Company, The | Reissert compounds as anti-hiv agents |
DE4142322A1 (de) * | 1991-12-20 | 1993-07-01 | Hoechst Ag | Chinoxaline, verfahren zu ihrer herstellung und ihreverwendung |
TW304945B (xx) * | 1992-06-27 | 1997-05-11 | Hoechst Ag |
-
1994
- 1994-08-16 DE DE4428932A patent/DE4428932A1/de not_active Withdrawn
-
1995
- 1995-08-07 NZ NZ272730A patent/NZ272730A/en unknown
- 1995-08-10 DE DE59510318T patent/DE59510318D1/de not_active Expired - Lifetime
- 1995-08-10 ES ES95112585T patent/ES2179857T3/es not_active Expired - Lifetime
- 1995-08-10 HR HRP4428932.4A patent/HRP950446A2/hr not_active Application Discontinuation
- 1995-08-10 DK DK95112585T patent/DK0697405T3/da active
- 1995-08-10 PT PT95112585T patent/PT697405E/pt unknown
- 1995-08-10 AT AT95112585T patent/ATE222239T1/de not_active IP Right Cessation
- 1995-08-10 EP EP95112585A patent/EP0697405B1/de not_active Expired - Lifetime
- 1995-08-14 AU AU28531/95A patent/AU710238B2/en not_active Ceased
- 1995-08-14 FI FI953841A patent/FI953841A/fi unknown
- 1995-08-14 US US08/515,556 patent/US5798365A/en not_active Expired - Lifetime
- 1995-08-14 SK SK1006-95A patent/SK100695A3/sk unknown
- 1995-08-15 HU HU9502403A patent/HUT73133A/hu unknown
- 1995-08-15 IL IL11493795A patent/IL114937A0/xx unknown
- 1995-08-15 CN CN95115281A patent/CN1123275A/zh active Pending
- 1995-08-15 CA CA002156128A patent/CA2156128A1/en not_active Abandoned
- 1995-08-15 JP JP22863995A patent/JP3860618B2/ja not_active Expired - Fee Related
- 1995-08-15 ZA ZA956798A patent/ZA956798B/xx unknown
- 1995-08-15 CZ CZ952090A patent/CZ209095A3/cs unknown
- 1995-08-15 NO NO953204A patent/NO306296B1/no not_active IP Right Cessation
- 1995-08-16 SI SI9500260A patent/SI9500260A/sl unknown
- 1995-08-16 PL PL95310030A patent/PL310030A1/xx unknown
- 1995-08-16 KR KR1019950025532A patent/KR960007567A/ko not_active Application Discontinuation
- 1995-08-28 TW TW084108914A patent/TW407151B/zh active
Also Published As
Publication number | Publication date |
---|---|
ES2179857T3 (es) | 2003-02-01 |
NZ272730A (en) | 1998-01-26 |
TW407151B (en) | 2000-10-01 |
DE4428932A1 (de) | 1996-02-22 |
CA2156128A1 (en) | 1996-02-17 |
CN1123275A (zh) | 1996-05-29 |
HUT73133A (en) | 1996-06-28 |
US5798365A (en) | 1998-08-25 |
SK100695A3 (en) | 1996-06-05 |
NO953204D0 (no) | 1995-08-15 |
KR960007567A (ko) | 1996-03-22 |
HU9502403D0 (en) | 1995-10-30 |
JPH0859621A (ja) | 1996-03-05 |
CZ209095A3 (en) | 1996-03-13 |
AU2853195A (en) | 1996-02-29 |
EP0697405A1 (de) | 1996-02-21 |
AU710238B2 (en) | 1999-09-16 |
SI9500260A (en) | 1996-02-29 |
ZA956798B (en) | 1996-03-19 |
EP0697405B1 (de) | 2002-08-14 |
JP3860618B2 (ja) | 2006-12-20 |
DK0697405T3 (da) | 2002-12-16 |
NO306296B1 (no) | 1999-10-18 |
PL310030A1 (en) | 1996-02-19 |
NO953204L (no) | 1996-02-19 |
DE59510318D1 (de) | 2002-09-19 |
PT697405E (pt) | 2002-12-31 |
FI953841A (fi) | 1996-02-17 |
IL114937A0 (en) | 1995-12-08 |
ATE222239T1 (de) | 2002-08-15 |
FI953841A0 (fi) | 1995-08-14 |
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Legal Events
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A1OB | Publication of a patent application | ||
AIPI | Request for the grant of a patent on the basis of a substantive examination of a patent application | ||
ODBC | Application rejected |