DK3174852T3 - ARYL HYDRAZIDES CONTAINING A 2-PYRIDON PART AS SELECTIVE ANTIBACTERIALS - Google Patents
ARYL HYDRAZIDES CONTAINING A 2-PYRIDON PART AS SELECTIVE ANTIBACTERIALS Download PDFInfo
- Publication number
- DK3174852T3 DK3174852T3 DK15750274.1T DK15750274T DK3174852T3 DK 3174852 T3 DK3174852 T3 DK 3174852T3 DK 15750274 T DK15750274 T DK 15750274T DK 3174852 T3 DK3174852 T3 DK 3174852T3
- Authority
- DK
- Denmark
- Prior art keywords
- alkyl
- oxo
- 4alkyl
- carboxylic acid
- hydrogen
- Prior art date
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- 229940088710 antibiotic agent Drugs 0.000 title abstract description 13
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 title abstract description 5
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 title 1
- 208000015181 infectious disease Diseases 0.000 claims abstract description 30
- 238000000034 method Methods 0.000 claims abstract description 28
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 230000008569 process Effects 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 257
- 229910052739 hydrogen Inorganic materials 0.000 claims description 188
- 239000001257 hydrogen Substances 0.000 claims description 188
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 120
- 229910052736 halogen Inorganic materials 0.000 claims description 116
- -1 -COOR 12 Chemical group 0.000 claims description 115
- 150000002367 halogens Chemical class 0.000 claims description 99
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 72
- 125000000217 alkyl group Chemical group 0.000 claims description 66
- 150000003839 salts Chemical class 0.000 claims description 47
- 239000012453 solvate Substances 0.000 claims description 42
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- RGZCKPXTNJAWMR-UHFFFAOYSA-N 1,2-dihydro-1-methyl-2-oxopyridine-5-carboxylic acid Natural products CN1C=C(C(O)=O)C=CC1=O RGZCKPXTNJAWMR-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims 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 description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 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 description 2
- 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 description 2
- 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 description 2
- 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 2
- 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 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 18
- 125000003545 alkoxy group Chemical group 0.000 claims 12
- 150000002431 hydrogen Chemical class 0.000 claims 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 125000003118 aryl group Chemical group 0.000 claims 4
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- 241000588626 Acinetobacter baumannii Species 0.000 abstract description 37
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 11
- 238000011282 treatment Methods 0.000 abstract description 11
- 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 64
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 239000000243 solution Substances 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 45
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
- 239000007787 solid Substances 0.000 description 35
- 230000002829 reductive effect Effects 0.000 description 34
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
- 235000019439 ethyl acetate Nutrition 0.000 description 32
- 229940093499 ethyl acetate Drugs 0.000 description 31
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 31
- 239000012044 organic layer Substances 0.000 description 28
- NQIGVOXZWAROOG-UHFFFAOYSA-N 1-methyl-6-oxopyridine-2-carboxylic acid Chemical compound CN1C(C(O)=O)=CC=CC1=O NQIGVOXZWAROOG-UHFFFAOYSA-N 0.000 description 27
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 25
- 239000007832 Na2SO4 Substances 0.000 description 24
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 24
- 229910052938 sodium sulfate Inorganic materials 0.000 description 24
- 235000011152 sodium sulphate Nutrition 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 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
- 239000007821 HATU Substances 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 125000005843 halogen group Chemical group 0.000 description 20
- 229910052731 fluorine Inorganic materials 0.000 description 19
- 239000011737 fluorine Substances 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 17
- 125000001153 fluoro group Chemical group F* 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- FEKUXLUOKFSMRO-UHFFFAOYSA-N (4-fluorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=C(F)C=C1 FEKUXLUOKFSMRO-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 241000894006 Bacteria Species 0.000 description 12
- 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
- 239000005457 ice water Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- 239000012299 nitrogen atmosphere Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 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 8
- 206010035664 Pneumonia Diseases 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- XUKWOJNDLIOXSC-UHFFFAOYSA-N 1-methyl-2-oxopyridine-4-carboxylic acid Chemical compound CN1C=CC(C(O)=O)=CC1=O XUKWOJNDLIOXSC-UHFFFAOYSA-N 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-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
- 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
- 238000007254 oxidation reaction Methods 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 208000019206 urinary tract infection Diseases 0.000 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 description 5
- 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 description 5
- 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 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 description 5
- 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 description 5
- 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 description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 5
- 241000194031 Enterococcus faecium Species 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- 206010040047 Sepsis Diseases 0.000 description 5
- 208000009470 Ventilator-Associated Pneumonia Diseases 0.000 description 5
- 208000037815 bloodstream infection Diseases 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 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 description 4
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 4
- 241000589291 Acinetobacter Species 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 4
- 241000588915 Klebsiella aerogenes Species 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 208000031650 Surgical Wound Infection Diseases 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 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 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 208000002551 irritable bowel syndrome Diseases 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 238000012746 preparative thin layer chromatography Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 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 description 3
- UTHKVSFOOCIQAL-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]-6-oxopyridine-3-carboxylic acid Chemical compound C1=C(C(=O)O)C=CC(=O)N1CC1=CC=CC=C1Cl UTHKVSFOOCIQAL-UHFFFAOYSA-N 0.000 description 3
- UUOJFUONBLNEEP-UHFFFAOYSA-N 1-[(3-methylphenyl)methyl]-2-oxopyridine-3-carboxylic acid Chemical compound CC1=CC=CC(CN2C(C(C(O)=O)=CC=C2)=O)=C1 UUOJFUONBLNEEP-UHFFFAOYSA-N 0.000 description 3
- WWQITSXZESSTGW-UHFFFAOYSA-N 1-benzyl-4,6-dimethyl-2-oxopyridine-3-carboxylic acid Chemical compound O=C1C(C(O)=O)=C(C)C=C(C)N1CC1=CC=CC=C1 WWQITSXZESSTGW-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 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 3
- 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 3
- 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
- ORRDAPKKXQZMDX-UHFFFAOYSA-N 2-[2-[(4-fluoroanilino)carbamoyl]-6-oxopyridin-1-yl]acetamide Chemical compound FC1=CC=C(C=C1)NNC(=O)C=1N(C(C=CC=1)=O)CC(=O)N ORRDAPKKXQZMDX-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- ICBDLOCCWXMMTM-UHFFFAOYSA-N N'-(4-fluorophenyl)-1-(2-methoxyethyl)-6-oxopyridine-2-carbohydrazide Chemical compound FC1=CC=C(C=C1)NNC(=O)C=1N(C(C=CC=1)=O)CCOC ICBDLOCCWXMMTM-UHFFFAOYSA-N 0.000 description 3
- RVZCRYZPKJKJKX-UHFFFAOYSA-N N'-(4-fluorophenyl)-1-methyl-2-oxopyridine-3-carbohydrazide Chemical compound FC1=CC=C(C=C1)NNC(=O)C=1C(N(C=CC=1)C)=O RVZCRYZPKJKJKX-UHFFFAOYSA-N 0.000 description 3
- ZUHAJBXAXKAMMT-UHFFFAOYSA-N N'-(4-fluorophenyl)-6-oxo-1-prop-2-ynylpyridine-2-carbohydrazide Chemical compound FC1=CC=C(C=C1)NNC(=O)C=1N(C(C=CC=1)=O)CC#C ZUHAJBXAXKAMMT-UHFFFAOYSA-N 0.000 description 3
- XCWXXSNDTLOKOO-UHFFFAOYSA-N O=C1C=CC=C(N1CC#C)C(=O)OC Chemical compound O=C1C=CC=C(N1CC#C)C(=O)OC XCWXXSNDTLOKOO-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- HDZGZJOAFYSQFH-UHFFFAOYSA-N ethyl 1-(2-methoxyethyl)-6-oxopyridine-2-carboxylate Chemical compound C(C)OC(=O)C=1N(C(C=CC=1)=O)CCOC HDZGZJOAFYSQFH-UHFFFAOYSA-N 0.000 description 3
- RNSNJQKLQAEJKH-UHFFFAOYSA-N ethyl 1-ethyl-6-oxopyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC(=O)N1CC RNSNJQKLQAEJKH-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
- 125000002346 iodo group Chemical group I* 0.000 description 3
- 150000002500 ions Chemical class 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
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Classifications
-
- 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
-
- 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
-
- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
|---|---|
| DK3174852T3 true DK3174852T3 (en) | 2018-09-10 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK15750274.1T DK3174852T3 (en) | 2014-07-30 | 2015-07-29 | ARYL HYDRAZIDES CONTAINING A 2-PYRIDON PART AS SELECTIVE ANTIBACTERIALS |
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|---|---|
| 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 |
|---|---|---|---|---|
| PE20180796A1 (es) | 2015-10-27 | 2018-05-09 | Hoffmann La Roche | Macrociclos peptidicos 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 |
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| JPH0399058A (ja) * | 1989-09-09 | 1991-04-24 | Kaken Pharmaceut Co Ltd | 複素５員環化合物 |
| CN100486576C (zh) * | 2002-02-14 | 2009-05-13 | 法玛西雅公司 | 作为p38map激酶调节剂的取代吡啶酮类 |
| SE0203348D0 (sv) * | 2002-11-12 | 2002-11-12 | Astrazeneca Ab | Novel compounds |
| TW200500341A (en) * | 2002-11-12 | 2005-01-01 | Astrazeneca Ab | Novel compounds |
| CN101014571A (zh) * | 2004-01-30 | 2007-08-08 | 默克公司 | 用作hiv整合酶抑制剂的n－苄基－3,4－二羟基吡啶－2－羧酰胺类和n－苄基－2,3－二羟基吡啶－4－羧酰胺类化合物 |
| WO2012051708A1 (en) * | 2010-10-21 | 2012-04-26 | The University Of British Columbia | Anti-bacterial pyruvate kinase modulator compounds, compositions, uses, and methods |
| JP2016525103A (ja) * | 2013-07-14 | 2016-08-22 | アシロス・エ／エス | リベス種から誘導可能な新たな生物活性アルカロイドおよびアルカロイド画分 |
| KR102076820B1 (ko) * | 2013-10-21 | 2020-02-13 | 주식회사 대웅테라퓨틱스 | 신규한 항진균성 옥소다이하이드로피리딘카보하이드라자이드 유도체 |
-
2015
- 2015-07-29 MX MX2017001280A patent/MX2017001280A/es unknown
- 2015-07-29 PT PT15750274T patent/PT3174852T/pt unknown
- 2015-07-29 CA CA2955559A patent/CA2955559A1/en not_active Abandoned
- 2015-07-29 DK DK15750274.1T patent/DK3174852T3/en active
- 2015-07-29 US US15/500,333 patent/US9840467B2/en active Active
- 2015-07-29 JP JP2017505253A patent/JP2017523197A/ja active Pending
- 2015-07-29 RU RU2017101154A patent/RU2017101154A/ru not_active Application Discontinuation
- 2015-07-29 CN CN201580041697.XA patent/CN106660962A/zh active Pending
- 2015-07-29 KR KR1020177003051A patent/KR20170038822A/ko not_active Withdrawn
- 2015-07-29 EP EP15750274.1A patent/EP3174852B1/en active Active
- 2015-07-29 AU AU2015295380A patent/AU2015295380A1/en not_active Abandoned
- 2015-07-29 WO PCT/EP2015/067345 patent/WO2016016291A1/en not_active Ceased
- 2015-07-29 PE PE2017000133A patent/PE20170430A1/es not_active Application Discontinuation
- 2015-07-29 PL PL15750274T patent/PL3174852T3/pl unknown
- 2015-07-29 BR BR112017001803A patent/BR112017001803A2/pt not_active Application Discontinuation
- 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 |
|---|---|
| PE20170430A1 (es) | 2017-04-13 |
| EP3174852B1 (en) | 2018-07-18 |
| ES2687826T3 (es) | 2018-10-29 |
| AU2015295380A1 (en) | 2017-02-02 |
| EP3174852A1 (en) | 2017-06-07 |
| US9840467B2 (en) | 2017-12-12 |
| CL2017000231A1 (es) | 2017-07-28 |
| KR20170038822A (ko) | 2017-04-07 |
| MX2017001280A (es) | 2017-06-20 |
| RU2017101154A (ru) | 2018-08-30 |
| CN106660962A (zh) | 2017-05-10 |
| PL3174852T3 (pl) | 2018-11-30 |
| RU2017101154A3 (enExample) | 2019-01-30 |
| BR112017001803A2 (pt) | 2018-02-14 |
| WO2016016291A1 (en) | 2016-02-04 |
| US20170217887A1 (en) | 2017-08-03 |
| CA2955559A1 (en) | 2016-02-04 |
| PH12017500057A1 (en) | 2017-05-15 |
| JP2017523197A (ja) | 2017-08-17 |
| PT3174852T (pt) | 2018-10-23 |
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