ES2687826T3 - Arilhidrazidas que contienen una fracción de 2-piridona como agentes antibacterianos selectivos - Google Patents
Arilhidrazidas que contienen una fracción de 2-piridona como agentes antibacterianos selectivos Download PDFInfo
- Publication number
- ES2687826T3 ES2687826T3 ES15750274.1T ES15750274T ES2687826T3 ES 2687826 T3 ES2687826 T3 ES 2687826T3 ES 15750274 T ES15750274 T ES 15750274T ES 2687826 T3 ES2687826 T3 ES 2687826T3
- Authority
- ES
- Spain
- Prior art keywords
- 4alkyl
- 6alkyl
- oxo
- carboxylic acid
- hydrazide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000003242 anti bacterial agent Substances 0.000 title claims description 15
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 255
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 192
- 239000001257 hydrogen Substances 0.000 claims abstract description 192
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 166
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 144
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 135
- -1 2,4,6-trichlorophenyl Chemical group 0.000 claims abstract description 130
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 119
- 150000002367 halogens Chemical class 0.000 claims abstract description 102
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 67
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 239000012453 solvate Substances 0.000 claims abstract description 42
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 17
- 125000001424 substituent group Chemical group 0.000 claims abstract description 15
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 11
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- UWBIFBXYDQJWOD-UHFFFAOYSA-N 1-[(3-methylphenyl)methyl]-2-oxo-n'-[3-(trifluoromethyl)phenyl]pyridine-3-carbohydrazide Chemical compound CC1=CC=CC(CN2C(C(C(=O)NNC=3C=C(C=CC=3)C(F)(F)F)=CC=C2)=O)=C1 UWBIFBXYDQJWOD-UHFFFAOYSA-N 0.000 claims abstract description 6
- ZXCNQNFWZBDWOM-UHFFFAOYSA-N 1-benzyl-4,6-dimethyl-2-oxo-N'-phenylpyridine-3-carbohydrazide Chemical compound C1(=CC=CC=C1)NNC(=O)C=1C(N(C(=CC=1C)C)CC1=CC=CC=C1)=O ZXCNQNFWZBDWOM-UHFFFAOYSA-N 0.000 claims abstract description 6
- WSDUAZUBRUEIIL-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]-n'-methyl-6-oxo-n'-phenylpyridine-3-carbohydrazide Chemical compound C=1C=CC=CC=1N(C)NC(=O)C(=C1)C=CC(=O)N1CC1=CC=CC=C1Cl WSDUAZUBRUEIIL-UHFFFAOYSA-N 0.000 claims abstract description 5
- MAZIROXFIAJVQN-UHFFFAOYSA-N 1-benzyl-2-oxo-n'-[2-(trifluoromethyl)phenyl]pyridine-3-carbohydrazide Chemical compound FC(F)(F)C1=CC=CC=C1NNC(=O)C(C1=O)=CC=CN1CC1=CC=CC=C1 MAZIROXFIAJVQN-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims abstract 5
- 125000002950 monocyclic group Chemical group 0.000 claims abstract 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 59
- 241000588626 Acinetobacter baumannii Species 0.000 claims description 36
- 208000015181 infectious disease Diseases 0.000 claims description 32
- NQIGVOXZWAROOG-UHFFFAOYSA-N 1-methyl-6-oxopyridine-2-carboxylic acid Chemical compound CN1C(C(O)=O)=CC=CC1=O NQIGVOXZWAROOG-UHFFFAOYSA-N 0.000 claims description 31
- 238000000034 method Methods 0.000 claims description 29
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- RGZCKPXTNJAWMR-UHFFFAOYSA-N 1-methyl-6-oxopyridine-3-carboxylic acid Chemical compound CN1C=C(C(O)=O)C=CC1=O RGZCKPXTNJAWMR-UHFFFAOYSA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- FXKINDGWHBDPDY-UHFFFAOYSA-N 1-(2-amino-2-oxoethyl)-6-oxopyridine-2-carboxylic acid Chemical compound NC(CN1C(=CC=CC1=O)C(=O)O)=O FXKINDGWHBDPDY-UHFFFAOYSA-N 0.000 claims description 5
- DAUBRVMDSQBYFO-UHFFFAOYSA-N 1-(2-methoxyethyl)-6-oxopyridine-2-carboxylic acid Chemical compound COCCN1C(C(O)=O)=CC=CC1=O DAUBRVMDSQBYFO-UHFFFAOYSA-N 0.000 claims description 5
- GWCRVVADHPQNNB-UHFFFAOYSA-N 1-ethyl-6-oxopyridine-2-carboxylic acid Chemical compound CCN1C(C(O)=O)=CC=CC1=O GWCRVVADHPQNNB-UHFFFAOYSA-N 0.000 claims description 5
- WXNLKTSGVAMFOB-UHFFFAOYSA-N 1-methyl-2-oxo-n'-(2,4,6-trichlorophenyl)pyridine-4-carbohydrazide Chemical compound O=C1N(C)C=CC(C(=O)NNC=2C(=CC(Cl)=CC=2Cl)Cl)=C1 WXNLKTSGVAMFOB-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- SAXVYJMTJVYCCT-UHFFFAOYSA-N 1-(difluoromethyl)-6-oxopyridine-2-carboxylic acid Chemical compound FC(N1C(=CC=CC1=O)C(=O)O)F SAXVYJMTJVYCCT-UHFFFAOYSA-N 0.000 claims description 4
- HZEFWASVLRGDDY-UHFFFAOYSA-N 1-benzyl-6-oxopyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(=O)N1CC1=CC=CC=C1 HZEFWASVLRGDDY-UHFFFAOYSA-N 0.000 claims description 4
- UENKXQVSDZHOQI-UHFFFAOYSA-N 1-ethyl-2-oxopyridine-3-carboxylic acid Chemical compound CCN1C=CC=C(C(O)=O)C1=O UENKXQVSDZHOQI-UHFFFAOYSA-N 0.000 claims description 4
- DFAQSHLYVFQOJM-UHFFFAOYSA-N 1-methyl-2-oxopyridine-3-carboxylic acid Chemical compound CN1C=CC=C(C(O)=O)C1=O DFAQSHLYVFQOJM-UHFFFAOYSA-N 0.000 claims description 4
- RYFABALCQHPBIM-UHFFFAOYSA-N 4-methoxy-1-methyl-6-oxopyridine-2-carboxylic acid Chemical compound COC1=CC(=O)N(C)C(=C1)C(O)=O RYFABALCQHPBIM-UHFFFAOYSA-N 0.000 claims description 4
- YPTMUSIOZIZXCC-UHFFFAOYSA-N 6-oxo-1-(2,2,2-trifluoroethyl)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(=O)N1CC(F)(F)F YPTMUSIOZIZXCC-UHFFFAOYSA-N 0.000 claims description 4
- QSHLSJXLGXSZKT-UHFFFAOYSA-N 1-(cyclopropylmethyl)-6-oxopyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(=O)N1CC1CC1 QSHLSJXLGXSZKT-UHFFFAOYSA-N 0.000 claims description 3
- UXQGAMVICZDTEV-UHFFFAOYSA-N 1-[2-(dimethylamino)-2-oxoethyl]-6-oxopyridine-2-carboxylic acid Chemical compound CN(C(CN1C(=CC=CC1=O)C(=O)O)=O)C UXQGAMVICZDTEV-UHFFFAOYSA-N 0.000 claims description 3
- XUKWOJNDLIOXSC-UHFFFAOYSA-N 1-methyl-2-oxopyridine-4-carboxylic acid Chemical compound CN1C=CC(C(O)=O)=CC1=O XUKWOJNDLIOXSC-UHFFFAOYSA-N 0.000 claims description 3
- IQRMMSOCEVXJTF-UHFFFAOYSA-N 1-methyl-6-oxo-N'-phenylpyridine-2-carbohydrazide Chemical compound C1(=CC=CC=C1)NNC(=O)C=1N(C(C=CC=1)=O)C IQRMMSOCEVXJTF-UHFFFAOYSA-N 0.000 claims description 3
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 3
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
- AUQZOHFAPVNKRN-UHFFFAOYSA-N 5-ethyl-1-methyl-6-oxopyridine-2-carboxylic acid Chemical compound CCC1=CC=C(C(O)=O)N(C)C1=O AUQZOHFAPVNKRN-UHFFFAOYSA-N 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 95
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 71
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 61
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 239000011541 reaction mixture Substances 0.000 description 56
- 239000000243 solution Substances 0.000 description 48
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 35
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 33
- 230000002829 reductive effect Effects 0.000 description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
- 239000007832 Na2SO4 Substances 0.000 description 32
- 235000019439 ethyl acetate Nutrition 0.000 description 32
- 229910052938 sodium sulfate Inorganic materials 0.000 description 32
- 235000011152 sodium sulphate Nutrition 0.000 description 32
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 239000011737 fluorine Substances 0.000 description 21
- 229910052731 fluorine Inorganic materials 0.000 description 21
- 239000007821 HATU Substances 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 125000005843 halogen group Chemical group 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 241000894006 Bacteria Species 0.000 description 16
- 239000005457 ice water Substances 0.000 description 16
- 125000001153 fluoro group Chemical group F* 0.000 description 15
- FEKUXLUOKFSMRO-UHFFFAOYSA-N (4-fluorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(F)C=C1 FEKUXLUOKFSMRO-UHFFFAOYSA-N 0.000 description 14
- 239000000203 mixture Substances 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 238000006467 substitution reaction Methods 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 9
- 229940088710 antibiotic agent Drugs 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 241000194031 Enterococcus faecium Species 0.000 description 8
- 241000588724 Escherichia coli Species 0.000 description 8
- 241000588915 Klebsiella aerogenes Species 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- 239000007822 coupling agent Substances 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- VRCWSYYXUCKEED-UHFFFAOYSA-N 6-Hydroxypicolinic acid Chemical compound OC(=O)C1=CC=CC(=O)N1 VRCWSYYXUCKEED-UHFFFAOYSA-N 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- GJLWQAUHCDNAEK-UHFFFAOYSA-N methyl 6-oxo-1h-pyridine-2-carboxylate Chemical compound COC(=O)C1=CC=CC(O)=N1 GJLWQAUHCDNAEK-UHFFFAOYSA-N 0.000 description 5
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 208000019206 urinary tract infection Diseases 0.000 description 5
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 206010035664 Pneumonia Diseases 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 238000012746 preparative thin layer chromatography Methods 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 241000589291 Acinetobacter Species 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 241000282414 Homo sapiens Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000031650 Surgical Wound Infection Diseases 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- BHTPNYOMVLJREU-UHFFFAOYSA-N ethyl 6-oxo-1h-pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC(=O)N1 BHTPNYOMVLJREU-UHFFFAOYSA-N 0.000 description 3
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 3
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 3
- 244000052769 pathogen Species 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 235000011181 potassium carbonates Nutrition 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- RIDRXGOBXZLKHZ-NZUANIILSA-N (3R,9S,12S,15S,18S,21S,24S,27R,30S,33S,36S,39S,42S,45S)-15,18,24,27,33-pentakis(2-aminoethyl)-30-(3-aminopropyl)-36-[(2S)-butan-2-yl]-42-[(1R)-1-hydroxyethyl]-9-(hydroxymethyl)-21,39-bis(1H-indol-3-ylmethyl)-12-methyl-1,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazatricyclo[43.3.0.03,7]octatetracontane-2,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecone Chemical compound CC[C@H](C)[C@@H]1NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H](NC(=O)[C@@H]2CCCN2C(=O)[C@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CCN)NC(=O)[C@@H](CCN)NC(=O)[C@H](CCCN)NC(=O)[C@H](CCN)NC1=O)[C@@H](C)O RIDRXGOBXZLKHZ-NZUANIILSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- SPWLGKANDBJTLJ-UHFFFAOYSA-N 1-ethyl-N'-(4-fluorophenyl)-2-oxopyridine-3-carbohydrazide Chemical compound FC1=CC=C(C=C1)NNC(=O)C=1C(N(C=CC=1)CC)=O SPWLGKANDBJTLJ-UHFFFAOYSA-N 0.000 description 2
- QMBPRTHEIXQSEI-UHFFFAOYSA-N 1-ethyl-N'-(4-fluorophenyl)-6-oxopyridine-2-carbohydrazide Chemical compound FC1=CC=C(C=C1)NNC(=O)C=1N(C(C=CC=1)=O)CC QMBPRTHEIXQSEI-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 directly attached to ring carbon atoms
- C07D211/90—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
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/86—Hydrazides; Thio or imino analogues thereof
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/86—Hydrazides; Thio or imino analogues thereof
- C07D213/87—Hydrazides; Thio or imino analogues thereof in position 3
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14179089 | 2014-07-30 | ||
| EP14179089 | 2014-07-30 | ||
| PCT/EP2015/067345 WO2016016291A1 (en) | 2014-07-30 | 2015-07-29 | Arylhydrazides containing a 2-pyridone moiety as selective antibacterial agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2687826T3 true ES2687826T3 (es) | 2018-10-29 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES15750274.1T Active ES2687826T3 (es) | 2014-07-30 | 2015-07-29 | Arilhidrazidas que contienen una fracción de 2-piridona como agentes antibacterianos selectivos |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US9840467B2 (enExample) |
| EP (1) | EP3174852B1 (enExample) |
| JP (1) | JP2017523197A (enExample) |
| KR (1) | KR20170038822A (enExample) |
| CN (1) | CN106660962A (enExample) |
| AU (1) | AU2015295380A1 (enExample) |
| BR (1) | BR112017001803A2 (enExample) |
| CA (1) | CA2955559A1 (enExample) |
| CL (1) | CL2017000231A1 (enExample) |
| DK (1) | DK3174852T3 (enExample) |
| ES (1) | ES2687826T3 (enExample) |
| MX (1) | MX2017001280A (enExample) |
| PE (1) | PE20170430A1 (enExample) |
| PH (1) | PH12017500057A1 (enExample) |
| PL (1) | PL3174852T3 (enExample) |
| PT (1) | PT3174852T (enExample) |
| RU (1) | RU2017101154A (enExample) |
| WO (1) | WO2016016291A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CR20180232A (es) | 2015-10-27 | 2018-05-31 | Hoffmann La Roche | Macrociclos peptídicos contra acinetobacter baumannii |
| ES2651943B2 (es) | 2016-07-29 | 2018-08-14 | ABAC Therapeutics, S.L. | Agentes antibacterianos de 2-pirrolidin fenilihidrazidas |
| US11505573B2 (en) | 2018-03-28 | 2022-11-22 | Hoffmann-La Roche Inc. | Peptide macrocycles against Acinetobacter baumannii |
| US11819532B2 (en) | 2018-04-23 | 2023-11-21 | Hoffmann-La Roche Inc. | Peptide macrocycles against Acinetobacter baumannii |
| WO2020169683A1 (en) * | 2019-02-19 | 2020-08-27 | Yncrea Hauts De France | Hydrazonopyrrolidine derivatives for use in preventing and/or treating disorders associated to acinetobacter baumannii |
| WO2020169682A1 (en) * | 2019-02-19 | 2020-08-27 | Yncrea Hauts De France | Hydrazide derivatives and their specific use as antibacterial agents by controlling acinetobacter baumannii bacterium |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0399058A (ja) * | 1989-09-09 | 1991-04-24 | Kaken Pharmaceut Co Ltd | 複素５員環化合物 |
| DE60330126D1 (de) * | 2002-02-14 | 2009-12-31 | Pharmacia Corp | Substituierte pyridinone als modulatoren für p38 map kinase |
| SE0203348D0 (sv) * | 2002-11-12 | 2002-11-12 | Astrazeneca Ab | Novel compounds |
| TW200500341A (en) * | 2002-11-12 | 2005-01-01 | Astrazeneca Ab | Novel compounds |
| JP2007519735A (ja) * | 2004-01-30 | 2007-07-19 | メルク エンド カムパニー インコーポレーテッド | Ｈｉｖインテグラーゼ阻害剤として有用であるｎ−ベンジル−３，４−ジヒドロキシピリジン−２−カルボキサミド及びｎ−ベンジル−２，３−ジヒドロキシピリジン−４−カルボキサミド化合物 |
| WO2012051708A1 (en) * | 2010-10-21 | 2012-04-26 | The University Of British Columbia | Anti-bacterial pyruvate kinase modulator compounds, compositions, uses, and methods |
| EP2859007B1 (en) * | 2013-07-14 | 2019-04-17 | Olle Svenssons Partiaffär AB | Alkaloid compositions from ribes species to treat conditions associated with mitochondrial function or inhibition of pde4, pde5 and ikk-beta |
| KR102076820B1 (ko) * | 2013-10-21 | 2020-02-13 | 주식회사 대웅테라퓨틱스 | 신규한 항진균성 옥소다이하이드로피리딘카보하이드라자이드 유도체 |
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2015
- 2015-07-29 CA CA2955559A patent/CA2955559A1/en not_active Abandoned
- 2015-07-29 KR KR1020177003051A patent/KR20170038822A/ko not_active Withdrawn
- 2015-07-29 PE PE2017000133A patent/PE20170430A1/es not_active Application Discontinuation
- 2015-07-29 PL PL15750274T patent/PL3174852T3/pl unknown
- 2015-07-29 RU RU2017101154A patent/RU2017101154A/ru not_active Application Discontinuation
- 2015-07-29 JP JP2017505253A patent/JP2017523197A/ja active Pending
- 2015-07-29 AU AU2015295380A patent/AU2015295380A1/en not_active Abandoned
- 2015-07-29 BR BR112017001803A patent/BR112017001803A2/pt not_active Application Discontinuation
- 2015-07-29 CN CN201580041697.XA patent/CN106660962A/zh active Pending
- 2015-07-29 DK DK15750274.1T patent/DK3174852T3/en active
- 2015-07-29 MX MX2017001280A patent/MX2017001280A/es unknown
- 2015-07-29 US US15/500,333 patent/US9840467B2/en active Active
- 2015-07-29 WO PCT/EP2015/067345 patent/WO2016016291A1/en not_active Ceased
- 2015-07-29 PT PT15750274T patent/PT3174852T/pt unknown
- 2015-07-29 EP EP15750274.1A patent/EP3174852B1/en active Active
- 2015-07-29 ES ES15750274.1T patent/ES2687826T3/es active Active
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2017
- 2017-01-09 PH PH12017500057A patent/PH12017500057A1/en unknown
- 2017-01-27 CL CL2017000231A patent/CL2017000231A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR112017001803A2 (pt) | 2018-02-14 |
| CA2955559A1 (en) | 2016-02-04 |
| MX2017001280A (es) | 2017-06-20 |
| JP2017523197A (ja) | 2017-08-17 |
| US9840467B2 (en) | 2017-12-12 |
| US20170217887A1 (en) | 2017-08-03 |
| WO2016016291A1 (en) | 2016-02-04 |
| EP3174852B1 (en) | 2018-07-18 |
| PL3174852T3 (pl) | 2018-11-30 |
| KR20170038822A (ko) | 2017-04-07 |
| PE20170430A1 (es) | 2017-04-13 |
| RU2017101154A3 (enExample) | 2019-01-30 |
| DK3174852T3 (en) | 2018-09-10 |
| PT3174852T (pt) | 2018-10-23 |
| CL2017000231A1 (es) | 2017-07-28 |
| EP3174852A1 (en) | 2017-06-07 |
| AU2015295380A1 (en) | 2017-02-02 |
| RU2017101154A (ru) | 2018-08-30 |
| PH12017500057A1 (en) | 2017-05-15 |
| CN106660962A (zh) | 2017-05-10 |
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