UA82198C2 - Хинолиновые производные и их использование в качестве микобактериальных ингибиторов, способ их получения, фармацевтическая композиция на их основе, промежуточное соединение - Google Patents
Хинолиновые производные и их использование в качестве микобактериальных ингибиторов, способ их получения, фармацевтическая композиция на их основе, промежуточное соединение Download PDFInfo
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- UA82198C2 UA82198C2 UAA200501778A UA2005001778A UA82198C2 UA 82198 C2 UA82198 C2 UA 82198C2 UA A200501778 A UAA200501778 A UA A200501778A UA 2005001778 A UA2005001778 A UA 2005001778A UA 82198 C2 UA82198 C2 UA 82198C2
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 198
- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims abstract description 5
- 238000000034 method Methods 0.000 title claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title abstract description 6
- 238000002360 preparation method Methods 0.000 title description 5
- 239000003112 inhibitor Substances 0.000 title 1
- 230000001052 transient effect Effects 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 73
- 239000001257 hydrogen Substances 0.000 claims abstract description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 33
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 239000002253 acid Substances 0.000 claims abstract description 21
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 18
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 10
- 208000027531 mycobacterial infectious disease Diseases 0.000 claims abstract description 10
- 239000003937 drug carrier Substances 0.000 claims abstract description 7
- 239000004480 active ingredient Substances 0.000 claims abstract description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 57
- 125000004432 carbon atom Chemical group C* 0.000 claims description 43
- 150000004820 halides Chemical class 0.000 claims description 38
- -1 2H-pyrrolyl Chemical group 0.000 claims description 29
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000001188 haloalkyl group Chemical group 0.000 claims description 20
- 125000004122 cyclic group Chemical group 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 125000004414 alkyl thio group Chemical group 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 7
- 125000003277 amino group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 229910052709 silver Inorganic materials 0.000 claims description 7
- 125000001425 triazolyl group Chemical group 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 125000005605 benzo group Chemical group 0.000 claims description 5
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 5
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 4
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 229940126601 medicinal product Drugs 0.000 claims description 3
- 229910052759 nickel Inorganic materials 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- HGUAWYGZOVFIAB-UHFFFAOYSA-N 1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(2-fluorophenyl)-1-phenylbutan-2-ol Chemical compound COC1=NC2=CC=C(Br)C=C2C=C1C(C(O)(CCN(C)C)C=1C(=CC=CC=1)F)C1=CC=CC=C1 HGUAWYGZOVFIAB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 2
- 125000004149 thio group Chemical group *S* 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims 5
- 230000000996 additive effect Effects 0.000 claims 3
- 125000004364 3-pyrrolinyl group Chemical group [H]C1=C([H])C([H])([H])N(*)C1([H])[H] 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 claims 1
- 229910052789 astatine Inorganic materials 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 13
- 201000010099 disease Diseases 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 230000001717 pathogenic effect Effects 0.000 abstract description 4
- 125000001246 bromo group Chemical group Br* 0.000 abstract description 2
- 241000186367 Mycobacterium avium Species 0.000 abstract 1
- 241000186366 Mycobacterium bovis Species 0.000 abstract 1
- 241000187492 Mycobacterium marinum Species 0.000 abstract 1
- 241000187479 Mycobacterium tuberculosis Species 0.000 abstract 1
- 125000000815 N-oxide group Chemical group 0.000 abstract 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
- 239000000243 solution Substances 0.000 description 47
- 239000002904 solvent Substances 0.000 description 39
- 230000015572 biosynthetic process Effects 0.000 description 31
- 238000003786 synthesis reaction Methods 0.000 description 30
- 150000003254 radicals Chemical class 0.000 description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 26
- 239000003480 eluent Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 19
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 239000002585 base Substances 0.000 description 13
- 239000013049 sediment Substances 0.000 description 13
- 201000008827 tuberculosis Diseases 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000005457 ice water Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
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- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 7
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 6
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 6
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
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- 229940126543 compound 14 Drugs 0.000 description 6
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 6
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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
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- 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
- A61P31/04—Antibacterial agents
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- 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
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- C07D231/12—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
-
- 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
-
- 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
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
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- 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
- C07D405/06—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 carbon chain containing only aliphatic carbon atoms
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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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US39871102P | 2002-07-25 | 2002-07-25 | |
PCT/EP2003/050322 WO2004011436A1 (en) | 2002-07-25 | 2003-07-18 | Quinoline derivatives and their use as mycobacterial inhibitors |
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Families Citing this family (92)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DK1711181T3 (da) | 2004-01-23 | 2010-02-01 | Janssen Pharmaceutica Nv | Quinolin-derivater og anvendelse af disse som mycobakterielle inhibitorer |
US7338949B2 (en) * | 2004-01-23 | 2008-03-04 | Janssen Pharmaceutica N.V. | Mycobacterial inhibitors |
DE602005006744D1 (de) | 2004-01-29 | 2008-06-26 | Janssen Pharmaceutica Nv | Chinolinderivate zur verwendung als inhibitoren von mycobakterien |
KR101371653B1 (ko) * | 2004-05-28 | 2014-03-07 | 얀센 파마슈티카 엔.브이. | 약물 내성 마이코박테리아 질환 치료를 위한 치환된 퀴놀린유도체의 용도 |
RU2418001C2 (ru) * | 2004-09-28 | 2011-05-10 | Янссен Фармацевтика Н.В. | Домен связывания бактериальной атр-синтазы |
EA009779B1 (ru) * | 2004-12-24 | 2008-04-28 | Янссен Фармацевтика Н.В. | Лечение латентного туберкулёза |
EE05394B1 (et) * | 2004-12-24 | 2011-04-15 | Janssen Pharmaceutica N.V. | Kinoliinihendid kasutamiseks latentse tuberkuloosi ravis |
KR101712835B1 (ko) * | 2005-05-25 | 2017-03-07 | 얀센 파마슈티카 엔.브이. | (알파 s, 베타 r)-6-브로모-알파-(2-(디메틸아미노)에틸)-2-메톡시-알파-1-나프탈레닐-베타-페닐-3-퀴놀린에탄올의 제조 방법 |
CA2528849C (en) | 2005-06-08 | 2014-01-14 | Janssen Pharmaceutica N.V. | Quinoline derivatives as antibacterial agents |
TWI380819B (zh) * | 2005-06-08 | 2013-01-01 | Janssen Pharmaceutica Nv | 用作抗細菌劑之喹啉衍生物 |
JP5349730B2 (ja) * | 2005-06-09 | 2013-11-20 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 抗バクテリア剤としてのキノリン誘導体 |
EA010601B1 (ru) * | 2005-06-09 | 2008-10-30 | Янссен Фармацевтика Н.В. | Производные хинолина в качестве антибактериальных агентов |
KR101318181B1 (ko) * | 2005-06-09 | 2013-10-16 | 얀센 파마슈티카 엔.브이. | 항균제로서의 퀴놀린 유도체 |
JO3270B1 (ar) * | 2005-06-28 | 2018-09-16 | Janssen Pharmaceutica Nv | مشتقات كوينولين بصفة عوامل مضادة للبكتيريا |
WO2007000434A1 (en) * | 2005-06-28 | 2007-01-04 | Janssen Pharmaceutica N.V. | Quinoline derivatives as antibacterial agents |
JO2752B1 (en) * | 2005-06-28 | 2014-03-15 | شركة جانسين فارماسوتيكا ان. في | Quinoline derivatives acting as antibacterial agents |
JO3077B1 (ar) * | 2005-07-28 | 2017-03-15 | Janssen Pharmaceutica Nv | مشتقات كوينولين مضادة للبكتيريا |
JO2952B1 (en) | 2005-08-03 | 2016-03-15 | جانسين فارماسوتيكا ان. في | Quinoline derivatives acting as antibacterial agents |
JO2837B1 (en) * | 2005-08-03 | 2014-09-15 | جانسن فارمسيتكا ان في | Quinoline derivatives acting as antibacterial agents |
JO2855B1 (en) * | 2005-08-03 | 2015-03-15 | شركة جانسين فارماسوتيكا ان. في | Quinoline derivatives acting as antibacterial agents |
US8686002B2 (en) | 2005-08-21 | 2014-04-01 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as binding partners for 5-HT5 receptors |
DE102005044817A1 (de) | 2005-09-20 | 2007-03-22 | Sanofi-Aventis Deutschland Gmbh | Substituierte 4-Phenyltetrahydroisochinoline, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, sowie sie enthaltendes Medikament |
UA97813C2 (ru) * | 2006-12-05 | 2012-03-26 | Янссен Фармацевтика Н.В. | Фумаратная соль (альфа s, бета r)-6-бром-альфа-[2-(диметиламино)этил]-2-метокси-альфа-1-нафталенил-бета-фенил-3-хинолинэтанола |
JO2683B1 (en) * | 2006-12-06 | 2013-03-03 | جانسين فارماسوتيكا ان. في | Quinoline antibacterial derivatives |
JO2684B1 (en) * | 2006-12-06 | 2013-03-03 | جانسين فارماسوتيكا ان في | Quinoline antibacterial derivatives |
JO3271B1 (ar) * | 2006-12-06 | 2018-09-16 | Janssen Pharmaceutica Nv | مشتقات الكوينولين المضادة للجراثيم |
JO2685B1 (en) * | 2006-12-06 | 2013-03-03 | جانسين فارماسوتيكا ان في | Quinoline antibacterial derivatives |
JO2970B1 (en) * | 2006-12-06 | 2016-03-15 | جانسين فارماسوتيكا ان. في | Quinoline antibacterial derivatives |
JO2725B1 (en) * | 2006-12-06 | 2013-09-15 | جانسين فارماسوتيكا ان. في | Quinoline antibacterial derivatives |
RU2404971C2 (ru) * | 2008-12-02 | 2010-11-27 | ЗАО "Фарм-Синтез" | Новые производные хинолина, способ их получения, их применение для лечения микобактериальных инфекций, фармацевтическая композиция на их основе |
CN102249935B (zh) | 2010-05-17 | 2015-05-20 | 中国人民解放军军事医学科学院毒物药物研究所 | 芳香2-丁醇类化合物及其医药用途 |
RU2486175C2 (ru) * | 2011-09-12 | 2013-06-27 | Закрытое Акционерное Общество "Фарм-Синтез" | Производные хинолина, в частности 5,6,7-замещенные 1-(2-хлорхинолин-3-ил)-4-диметиламино-2-(нафталин-1-ил)-1-фенилбутан-2-олы, способ получения и применение соединений |
EA038350B1 (ru) | 2012-04-27 | 2021-08-12 | Янссен Фармацевтика Нв | Антибактериальные хинолиновые производные |
PL2841425T3 (pl) | 2012-04-27 | 2016-10-31 | Antybakteryjne pochodne chinoliny | |
US9572809B2 (en) | 2012-07-18 | 2017-02-21 | Spero Trinem, Inc. | Combination therapy to treat Mycobacterium diseases |
EP2934498B1 (en) | 2012-12-21 | 2017-11-15 | Janssen Sciences Ireland UC | Antibacterial compounds |
RU2530493C1 (ru) * | 2013-04-22 | 2014-10-10 | Закрытое Акционерное Общество "Фарм-Синтез" | Производные хинолина, в частности 6,7-замещенные 1-(2-хлорхинолин-3-ил)-4-диметиламино-2-(нафталин-1-ил)-1-фенилбутан-2-олы, способ их получения и применение соединений для лечения инфекционных заболеваний микобактериальной природы, в частности туберкулеза |
CN105017147B (zh) * | 2014-04-30 | 2019-02-01 | 中国医学科学院药物研究所 | 一种回收和利用Bedaquiline立体化学异构体的方法 |
CN105085396B (zh) * | 2014-05-07 | 2017-08-08 | 国药集团国瑞药业有限公司 | 用于制备贝达喹啉的中间体及其制备方法和应用 |
CN105085395B (zh) * | 2014-05-07 | 2017-09-26 | 国药集团国瑞药业有限公司 | 贝达喹啉的制备方法 |
CN105198808B (zh) * | 2014-05-27 | 2017-08-25 | 北京万生药业有限责任公司 | 一种高效生产贝达喹啉的方法 |
CN105175329B (zh) * | 2014-06-10 | 2017-09-19 | 重庆圣华曦药业股份有限公司 | 一种贝达喹啉消旋体的合成路线及方法 |
CN105330595B (zh) * | 2014-07-14 | 2019-12-10 | 上海嘉坦医药科技有限公司 | 吡啶衍生物及其作为抗分支杆菌的应用 |
JP6362235B2 (ja) * | 2014-07-14 | 2018-07-25 | ツーセン ファーマシューティカル カンパニー リミテッド | ピリジン誘導体およびその抗マイコバクテリウムにおける使用 |
CN105440051B (zh) * | 2014-09-19 | 2019-07-05 | 重庆医药工业研究院有限责任公司 | 一种抗结核的噻吩吡啶衍生物 |
CZ2014708A3 (cs) | 2014-10-16 | 2016-04-27 | Zentiva, K.S. | Soli Bedaquilinu |
CZ201535A3 (cs) | 2015-01-21 | 2016-08-03 | Zentiva, K.S. | Nové možnosti chirální resoluce bedaquilinu |
CZ201533A3 (cs) | 2015-01-21 | 2016-08-03 | Zentiva, K.S. | Způsob izolace směsi enantiomerů |
CZ201534A3 (cs) | 2015-01-21 | 2016-08-03 | Zentiva, K.S. | Nové možnosti chirální resoluce bedaquilinu |
PL3250182T3 (pl) | 2015-01-27 | 2023-07-31 | Janssen Pharmaceutica Nv | Kompozycje dyspergowalne |
WO2016174673A1 (en) * | 2015-04-29 | 2016-11-03 | The State Of Israel, Ministry Of Agriculture & Rural Development, Agricultural Research Organization (Aro) (Volcani Center) | Anti-phytopathogenic compositions |
CN106279017A (zh) * | 2015-05-21 | 2017-01-04 | 重庆圣华曦药业股份有限公司 | 贝达喹啉晶型、组合物及其制备方法 |
CZ2015391A3 (cs) | 2015-06-09 | 2016-12-21 | Zentiva, K.S. | Sůl bedaquilinu s kyselinou citronovou |
ES2914681T3 (es) | 2015-07-02 | 2022-06-15 | Janssen Sciences Ireland Unlimited Co | Compuestos antibacterianos |
CN105061387A (zh) * | 2015-07-17 | 2015-11-18 | 苏州大学 | 二芳基醚类稠环类化合物、制备方法和用途 |
WO2017015793A1 (zh) * | 2015-07-24 | 2017-02-02 | 浙江海正药业股份有限公司 | 一种分离贝达喹啉非对映异构体a的方法 |
WO2017066926A1 (zh) * | 2015-10-20 | 2017-04-27 | 浙江海正药业股份有限公司 | 富马酸贝达喹啉的晶型及其制备方法 |
CN108473428B (zh) * | 2016-01-13 | 2021-07-23 | 上海嘉坦医药科技有限公司 | 一种吡啶衍生物类化合物的制备方法及其中间体和晶型 |
EP3423449B1 (en) * | 2016-03-03 | 2021-04-07 | Council of Scientific and Industrial Research | Substituted aurone alkaloids as anti-mycobacterial agents |
EP4148053A1 (en) * | 2016-03-07 | 2023-03-15 | The Global Alliance for TB Drug Development, Inc. | Antibacterial compounds and uses thereof |
CA3026010A1 (en) | 2016-06-16 | 2017-12-21 | Janssen Sciences Ireland Unlimited Company | Heterocyclic compounds as antibacterials |
CN109415349A (zh) | 2016-06-16 | 2019-03-01 | 爱尔兰詹森科学公司 | 杂环化合物作为抗细菌剂 |
MA47676A (fr) | 2017-03-01 | 2021-06-02 | Janssen Sciences Ireland Unlimited Co | Polythérapie |
SI3651736T1 (sl) * | 2017-07-14 | 2021-11-30 | Janssen Pharmaceutica Nv | Formulacije z dolgim delovanjem |
CN109384716B (zh) * | 2017-08-11 | 2021-06-29 | 海创药业股份有限公司 | 一种氘代喹啉化合物及其制备和用途 |
JP2022516671A (ja) | 2019-01-09 | 2022-03-01 | ヤンセン ファーマシューティカ エヌ.ベー. | 非結核性抗酸菌症の処置における組合せ |
WO2020161743A1 (en) | 2019-02-08 | 2020-08-13 | Mylan Laboratories Limited | Process for the preparation of bedaquiline fumarate |
EP4028399B1 (en) | 2019-09-13 | 2024-02-14 | Janssen Sciences Ireland Unlimited Company | Antibacterial compounds |
WO2021057190A1 (zh) * | 2019-09-29 | 2021-04-01 | 上海阳帆医药科技有限公司 | 喹啉类化合物、其制备方法和用途 |
KR20220071199A (ko) | 2019-09-30 | 2022-05-31 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 4-퀴놀리논 항균 화합물 |
KR20220075335A (ko) | 2019-09-30 | 2022-06-08 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 항균 화합물 |
CN110804016B (zh) * | 2019-12-05 | 2022-11-04 | 福建省微生物研究所 | 抗结核分枝杆菌的二芳基喹啉衍生物 |
GEP20247590B (en) | 2019-12-27 | 2024-02-12 | Tecnimede Soc Tecnico Medicinal Sa | Antibacterial quinolines |
KR102303635B1 (ko) | 2020-07-01 | 2021-09-17 | 동아에스티 주식회사 | (1r,2s)-1-(6-브로모-2-메톡시퀴놀린-3-일)-4-디메틸아미노-2-(1-나프틸)-1-페닐-부탄-2-올 및 이의 약제학적으로 허용 가능한 염의 제조방법 |
CA3184868A1 (en) | 2020-07-09 | 2022-01-13 | Rene Holm | Long-acting formulations |
WO2022008643A1 (en) | 2020-07-09 | 2022-01-13 | Janssen Pharmaceutica Nv | Long-acting formulations |
CA3182854A1 (en) | 2020-07-09 | 2022-01-13 | Rene Holm | Long-acting formulations |
KR20230107275A (ko) | 2020-11-12 | 2023-07-14 | 얀센 파마슈티카 엔.브이. | 비결핵성 마이코박테리아 질환의 치료에서 베다퀼린, 에탐부톨 및 마크롤라이드의 조합물 |
AU2022237769A1 (en) | 2021-03-16 | 2023-11-02 | Janssen Sciences Ireland Unlimited Company | Antibacterial compounds |
JP2024509998A (ja) | 2021-03-17 | 2024-03-05 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | 抗菌化合物 |
BR112023018655A2 (pt) | 2021-03-17 | 2023-12-12 | Janssen Sciences Ireland Unlimited Co | Compostos antibacterianos |
WO2022214520A1 (en) | 2021-04-07 | 2022-10-13 | Janssen Sciences Ireland Unlimited Company | Antibacterial compounds |
WO2022214519A1 (en) | 2021-04-07 | 2022-10-13 | Janssen Sciences Ireland Unlimited Company | Antibacterial compounds |
CA3223626A1 (en) | 2021-06-29 | 2023-01-05 | Augusto Eugenio Pardal Filipe | Heterocyclic compounds for the treatment of tuberculosis |
TW202325274A (zh) | 2021-10-28 | 2023-07-01 | 愛爾蘭商健生科學愛爾蘭無限公司 | 抗菌化合物 |
WO2023150747A1 (en) | 2022-02-07 | 2023-08-10 | Insmed Incorporated | Dry powder compositions of bedaquiline and salts and methods of use thereof |
CN114835641B (zh) * | 2022-05-07 | 2024-03-15 | 南京杰运医药科技有限公司 | 一种3-苄基-6-溴-2-甲氧基喹啉的合成方法 |
CN117050006A (zh) * | 2022-05-13 | 2023-11-14 | 广州嘉越医药科技有限公司 | 一种吡啶衍生物、中间体、制备方法和应用 |
WO2023232838A1 (en) | 2022-05-31 | 2023-12-07 | Janssen Pharmaceutica Nv | Bedaquiline for use in the treatment of leprosy |
WO2024068699A1 (en) | 2022-09-28 | 2024-04-04 | Janssen Pharmaceutica Nv | Long-acting formulations |
WO2024068693A1 (en) | 2022-09-28 | 2024-04-04 | Janssen Pharmaceutica Nv | Long-acting formulations |
WO2024089170A1 (en) | 2022-10-27 | 2024-05-02 | Janssen Sciences Ireland Unlimited Company | Antibacterial compounds |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5965572A (en) * | 1996-10-28 | 1999-10-12 | The United States Of America As Respresented By The Secretary Of The Army | Methods for treating antibiotic-resistant infections |
US6103905A (en) * | 1997-06-19 | 2000-08-15 | Sepracor, Inc. | Quinoline-indole antimicrobial agents, uses and compositions related thereto |
AU757059B2 (en) * | 1997-06-19 | 2003-01-30 | Sepracor, Inc. | Quinoline-indole antimicrobial agents, uses and compositions related thereto |
WO1999037365A1 (en) * | 1998-01-23 | 1999-07-29 | Fire Armour Pte Ltd. | Nozzle with axially and perpendicularly directed apertures |
WO1999037635A1 (en) * | 1998-01-26 | 1999-07-29 | Smithkline Beecham Plc | Quinoline derivatives as antibacterials |
US6819431B2 (en) * | 2001-07-06 | 2004-11-16 | Zygo Corporation | Polymer retarder |
EE05394B1 (et) * | 2004-12-24 | 2011-04-15 | Janssen Pharmaceutica N.V. | Kinoliinihendid kasutamiseks latentse tuberkuloosi ravis |
CA2528849C (en) * | 2005-06-08 | 2014-01-14 | Janssen Pharmaceutica N.V. | Quinoline derivatives as antibacterial agents |
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