EA015821B1 - Трициклические азотсодержащие соединения в качестве антибактериальных агентов - Google Patents
Трициклические азотсодержащие соединения в качестве антибактериальных агентов Download PDFInfo
- Publication number
- EA015821B1 EA015821B1 EA200970987A EA200970987A EA015821B1 EA 015821 B1 EA015821 B1 EA 015821B1 EA 200970987 A EA200970987 A EA 200970987A EA 200970987 A EA200970987 A EA 200970987A EA 015821 B1 EA015821 B1 EA 015821B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- dihydro
- methyl
- amino
- piperidinyl
- dione
- Prior art date
Links
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 title abstract 2
- 239000003242 anti bacterial agent Substances 0.000 title description 4
- -1 pyrrolidin-4-ylmethyl Chemical group 0.000 claims description 504
- 150000001875 compounds Chemical class 0.000 claims description 278
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 198
- 239000012458 free base Substances 0.000 claims description 123
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 118
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 34
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- 150000002431 hydrogen Chemical group 0.000 claims description 15
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 8
- 208000035143 Bacterial infection Diseases 0.000 claims description 8
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 8
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 201000008827 tuberculosis Diseases 0.000 claims description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000005647 linker group Chemical group 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000005605 benzo group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- 206010024971 Lower respiratory tract infections Diseases 0.000 claims description 2
- 206010062255 Soft tissue infection Diseases 0.000 claims description 2
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 206010040872 skin infection Diseases 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 208000019206 urinary tract infection Diseases 0.000 claims description 2
- 229910052720 vanadium Inorganic materials 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 210000003743 erythrocyte Anatomy 0.000 claims 2
- 240000008338 Nigella arvensis Species 0.000 claims 1
- 235000007413 Nigella arvensis Nutrition 0.000 claims 1
- 235000016698 Nigella sativa Nutrition 0.000 claims 1
- 241000588769 Proteus <enterobacteria> Species 0.000 claims 1
- 208000015181 infectious disease Diseases 0.000 claims 1
- 210000003491 skin Anatomy 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 4
- 229940088710 antibiotic agent Drugs 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 936
- 239000000243 solution Substances 0.000 description 226
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 221
- 239000011541 reaction mixture Substances 0.000 description 212
- 239000007787 solid Substances 0.000 description 189
- 239000000203 mixture Substances 0.000 description 177
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 164
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 146
- 239000000047 product Substances 0.000 description 146
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 144
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 111
- 238000005481 NMR spectroscopy Methods 0.000 description 91
- 239000000284 extract Substances 0.000 description 82
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 81
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
- 230000002829 reductive effect Effects 0.000 description 75
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 73
- 230000015572 biosynthetic process Effects 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
- 238000002360 preparation method Methods 0.000 description 66
- 229920006395 saturated elastomer Polymers 0.000 description 65
- 238000003786 synthesis reaction Methods 0.000 description 64
- 239000012043 crude product Substances 0.000 description 63
- 239000010410 layer Substances 0.000 description 63
- 239000000725 suspension Substances 0.000 description 59
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
- 239000012300 argon atmosphere Substances 0.000 description 55
- 238000006243 chemical reaction Methods 0.000 description 49
- 239000003921 oil Substances 0.000 description 49
- 235000019198 oils Nutrition 0.000 description 49
- 239000002904 solvent Substances 0.000 description 49
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 42
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- 150000002118 epoxides Chemical class 0.000 description 39
- 238000010898 silica gel chromatography Methods 0.000 description 39
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 37
- 239000007864 aqueous solution Substances 0.000 description 37
- 235000017557 sodium bicarbonate Nutrition 0.000 description 37
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 31
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 31
- 239000000741 silica gel Substances 0.000 description 31
- 229910002027 silica gel Inorganic materials 0.000 description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 25
- 238000000034 method Methods 0.000 description 25
- 239000012044 organic layer Substances 0.000 description 25
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- 229910052786 argon Inorganic materials 0.000 description 24
- 239000012074 organic phase Substances 0.000 description 21
- 229910000027 potassium carbonate Inorganic materials 0.000 description 21
- 239000007858 starting material Substances 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 20
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 20
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 20
- 150000001412 amines Chemical class 0.000 description 18
- 239000003208 petroleum Substances 0.000 description 18
- FNRMMDCDHWCQTH-UHFFFAOYSA-N 2-chloropyridine;3-chloropyridine;4-chloropyridine Chemical compound ClC1=CC=NC=C1.ClC1=CC=CN=C1.ClC1=CC=CC=N1 FNRMMDCDHWCQTH-UHFFFAOYSA-N 0.000 description 16
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 16
- 230000002209 hydrophobic effect Effects 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 229910052938 sodium sulfate Inorganic materials 0.000 description 16
- 235000011152 sodium sulphate Nutrition 0.000 description 16
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 239000012299 nitrogen atmosphere Substances 0.000 description 14
- 230000003647 oxidation Effects 0.000 description 14
- 238000007254 oxidation reaction Methods 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- 101000587820 Homo sapiens Selenide, water dikinase 1 Proteins 0.000 description 13
- 101000701815 Homo sapiens Spermidine synthase Proteins 0.000 description 13
- 102100030413 Spermidine synthase Human genes 0.000 description 13
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- 229910021529 ammonia Inorganic materials 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 239000006260 foam Substances 0.000 description 12
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 12
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 12
- 235000019341 magnesium sulphate Nutrition 0.000 description 12
- 239000003960 organic solvent Substances 0.000 description 12
- 239000012071 phase Substances 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- PDBXHPORMXSXKO-UHFFFAOYSA-N 8-benzyl-7-[2-[ethyl(2-hydroxyethyl)amino]ethyl]-1,3-dimethylpurine-2,6-dione;hydron;chloride Chemical class Cl.N=1C=2N(C)C(=O)N(C)C(=O)C=2N(CCN(CCO)CC)C=1CC1=CC=CC=C1 PDBXHPORMXSXKO-UHFFFAOYSA-N 0.000 description 11
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
- 239000012298 atmosphere Substances 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 238000006722 reduction reaction Methods 0.000 description 11
- 238000007363 ring formation reaction Methods 0.000 description 11
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000008346 aqueous phase Substances 0.000 description 10
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000004296 chiral HPLC Methods 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 8
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- 239000011347 resin Substances 0.000 description 8
- 229920005989 resin Polymers 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 150000002500 ions Chemical class 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 6
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- 235000019502 Orange oil Nutrition 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 230000029936 alkylation Effects 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 6
- 238000007429 general method Methods 0.000 description 6
- 239000010502 orange oil Substances 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000003981 vehicle Substances 0.000 description 6
- 239000005711 Benzoic acid Substances 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 235000010233 benzoic acid Nutrition 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000003245 coal Substances 0.000 description 5
- 150000002466 imines Chemical class 0.000 description 5
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- MBABOKRGFJTBAE-UHFFFAOYSA-N methyl methanesulfonate Chemical compound COS(C)(=O)=O MBABOKRGFJTBAE-UHFFFAOYSA-N 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 5
- 239000012453 solvate Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 4
- OMWBUWDHEZIMGQ-UHFFFAOYSA-N 2,3-dihydro-[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde Chemical compound O1CCOC2=C1C=C(C=O)N=C2 OMWBUWDHEZIMGQ-UHFFFAOYSA-N 0.000 description 4
- CKDDMXSSWVFPGO-UHFFFAOYSA-N 2-methylpent-3-enamide Chemical compound CC=CC(C)C(N)=O CKDDMXSSWVFPGO-UHFFFAOYSA-N 0.000 description 4
- HLTDBMHJSBSAOM-UHFFFAOYSA-N 2-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CC=N1 HLTDBMHJSBSAOM-UHFFFAOYSA-N 0.000 description 4
- MVQVNTPHUGQQHK-UHFFFAOYSA-N 3-pyridinemethanol Chemical compound OCC1=CC=CN=C1 MVQVNTPHUGQQHK-UHFFFAOYSA-N 0.000 description 4
- QBANBRWELABETG-UHFFFAOYSA-N 6-methoxy-2,4-dihydro-1h-pyrido[2,3-b]pyrazin-3-one Chemical compound N1CC(=O)NC2=NC(OC)=CC=C21 QBANBRWELABETG-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 4
- 102100029721 DnaJ homolog subfamily B member 1 Human genes 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- 101000866018 Homo sapiens DnaJ homolog subfamily B member 1 Proteins 0.000 description 4
- 101100293693 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) STO1 gene Proteins 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 101150050497 cbc1 gene Proteins 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- OZOAXHQNOFIFGD-UHFFFAOYSA-N manganese(2+) oxygen(2-) Chemical compound [O-2].[O-2].[Mn+2].[Mn+2] OZOAXHQNOFIFGD-UHFFFAOYSA-N 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 230000010287 polarization Effects 0.000 description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- CWKXDPPQCVWXAG-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound O1CCOC2=CC(C=O)=CC=C21 CWKXDPPQCVWXAG-UHFFFAOYSA-N 0.000 description 3
- UKFTXWKNVSVVCJ-UHFFFAOYSA-N 2-[(6-hydrazinylpyridazin-3-yl)-(2-hydroxyethyl)amino]ethanol;hydron;dichloride Chemical compound Cl.Cl.NNC1=CC=C(N(CCO)CCO)N=N1 UKFTXWKNVSVVCJ-UHFFFAOYSA-N 0.000 description 3
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 3
- DSOLBHZRAGNEPO-UHFFFAOYSA-N 3,4-dihydro-2h-pyrano[2,3-c]pyridine-6-carbaldehyde Chemical compound C1CCOC2=C1C=C(C=O)N=C2 DSOLBHZRAGNEPO-UHFFFAOYSA-N 0.000 description 3
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 3
- SAROZGMIXOZIBD-UHFFFAOYSA-N 5-bromo-3,4-dichloropyridazine Chemical class ClC1=NN=CC(Br)=C1Cl SAROZGMIXOZIBD-UHFFFAOYSA-N 0.000 description 3
- ZTQLIJKXJZMVIV-UHFFFAOYSA-N 5-fluoro-2,3-dihydro-1,4-benzodioxine-7-carbaldehyde Chemical compound O1CCOC2=C1C=C(C=O)C=C2F ZTQLIJKXJZMVIV-UHFFFAOYSA-N 0.000 description 3
- ZBNJTKYTUUSFFG-UHFFFAOYSA-N 6-fluoro-2,3-dihydro-1,4-benzodioxine-7-carbaldehyde Chemical compound O1CCOC2=C1C=C(F)C(C=O)=C2 ZBNJTKYTUUSFFG-UHFFFAOYSA-N 0.000 description 3
- WEPOCTWSRWLQLL-UHFFFAOYSA-N 6-methoxypyridine-2,3-diamine Chemical compound COC1=CC=C(N)C(N)=N1 WEPOCTWSRWLQLL-UHFFFAOYSA-N 0.000 description 3
- IKQSVZSSJQHCDT-UHFFFAOYSA-N 7-formyl-2,3-dihydro-1,4-benzodioxine-5-carbonitrile Chemical compound O1CCOC2=C1C=C(C=O)C=C2C#N IKQSVZSSJQHCDT-UHFFFAOYSA-N 0.000 description 3
- TYWLOTNSMFTIHR-UHFFFAOYSA-N 7-methoxy-3,4-dihydro-1h-1,8-naphthyridin-2-one Chemical compound C1CC(=O)NC2=NC(OC)=CC=C21 TYWLOTNSMFTIHR-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 229910017976 MgO 4 Inorganic materials 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100037580 Sesquipedalian-1 Human genes 0.000 description 3
- 101710169844 Sesquipedalian-1 Proteins 0.000 description 3
- XUHRMFGGSDZZOH-UHFFFAOYSA-N [1,2,5]thiadiazolo[3,4-b]pyridine-6-carbaldehyde Chemical compound C1=C(C=O)C=NC2=NSN=C21 XUHRMFGGSDZZOH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000005997 bromomethyl group Chemical group 0.000 description 3
- CQEYYJKEWSMYFG-UHFFFAOYSA-N butyl acrylate Chemical compound CCCCOC(=O)C=C CQEYYJKEWSMYFG-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 239000002198 insoluble material Substances 0.000 description 3
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000005191 phase separation Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- AYKGXSQEOUVZFP-UHFFFAOYSA-N tert-butyl n-[1-(1-chloro-3-phenylmethoxypropan-2-yl)piperidin-4-yl]-n-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)carbamate Chemical compound C=1C=2OCCOC=2C=NC=1CN(C(=O)OC(C)(C)C)C(CC1)CCN1C(CCl)COCC1=CC=CC=C1 AYKGXSQEOUVZFP-UHFFFAOYSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 3
- PLYRYAHDNXANEG-QMWPFBOUSA-N (2s,3s,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxy-n-methyloxolane-2-carboxamide Chemical compound O[C@@H]1[C@H](O)[C@@H](C(=O)NC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 PLYRYAHDNXANEG-QMWPFBOUSA-N 0.000 description 2
- IANQODMAGIGHED-UHFFFAOYSA-N (5-tert-butylsulfanyl-4-oxo-1h-pyridin-2-yl)methyl acetate Chemical compound CC(=O)OCC1=CC(=O)C(SC(C)(C)C)=CN1 IANQODMAGIGHED-UHFFFAOYSA-N 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
- PSFOJYIYLZRUPN-UHFFFAOYSA-N 1,3-dihydrofuro[3,4-c]pyridin-6-ylmethanol Chemical compound C1=NC(CO)=CC2=C1COC2 PSFOJYIYLZRUPN-UHFFFAOYSA-N 0.000 description 2
- QQZDUOGKYISWOC-UHFFFAOYSA-N 1,3-dihydrofuro[3,4-c]pyridine-6-carbaldehyde Chemical compound C1=NC(C=O)=CC2=C1COC2 QQZDUOGKYISWOC-UHFFFAOYSA-N 0.000 description 2
- OYNUAOUPWHPJGI-UHFFFAOYSA-N 1-(2,3-dihydroxypropyl)-7-methoxy-3,4-dihydro-1,8-naphthyridin-2-one Chemical compound C1CC(=O)N(CC(O)CO)C2=NC(OC)=CC=C21 OYNUAOUPWHPJGI-UHFFFAOYSA-N 0.000 description 2
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
- XSJAJQSDUJUNAI-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-6-carbaldehyde Chemical compound O=CC1=CC=C2CCOC2=C1 XSJAJQSDUJUNAI-UHFFFAOYSA-N 0.000 description 2
- JNGKZDHHCSGYTO-UHFFFAOYSA-N 2-(3,6-dichloropyridazin-4-yl)oxyethanol Chemical compound OCCOC1=CC(Cl)=NN=C1Cl JNGKZDHHCSGYTO-UHFFFAOYSA-N 0.000 description 2
- ZUMUBCINSCIPEZ-UHFFFAOYSA-N 2-(hydroxymethyl)-5-sulfanyl-1h-pyridin-4-one Chemical compound OCC1=CC(=O)C(S)=CN1 ZUMUBCINSCIPEZ-UHFFFAOYSA-N 0.000 description 2
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 2
- BETAXRDTVFAQMF-UHFFFAOYSA-N 2-[(6-methoxy-3-nitropyridin-2-yl)amino]propane-1,3-diol Chemical compound COC1=CC=C([N+]([O-])=O)C(NC(CO)CO)=N1 BETAXRDTVFAQMF-UHFFFAOYSA-N 0.000 description 2
- VKJQJNVYWGDEQN-UHFFFAOYSA-N 2-bromo-3-phenylmethoxypropanoic acid Chemical compound OC(=O)C(Br)COCC1=CC=CC=C1 VKJQJNVYWGDEQN-UHFFFAOYSA-N 0.000 description 2
- DVRGUTNVDGIKTP-UHFFFAOYSA-N 2-chloro-6-methoxy-3-nitropyridine Chemical compound COC1=CC=C([N+]([O-])=O)C(Cl)=N1 DVRGUTNVDGIKTP-UHFFFAOYSA-N 0.000 description 2
- QJGZSMHRBVQVTA-UHFFFAOYSA-N 2-ethenyl-8h-pyrimido[5,4-b][1,4]thiazin-7-one Chemical compound S1CC(=O)N=C2NC(C=C)=NC=C21 QJGZSMHRBVQVTA-UHFFFAOYSA-N 0.000 description 2
- WXWQJUNPKFWAEX-UHFFFAOYSA-N 2h-pyran-2-carbaldehyde Chemical compound O=CC1OC=CC=C1 WXWQJUNPKFWAEX-UHFFFAOYSA-N 0.000 description 2
- LJDQXQOPXOLCHL-UHFFFAOYSA-N 3,4,6-trichloropyridazine Chemical compound ClC1=CC(Cl)=C(Cl)N=N1 LJDQXQOPXOLCHL-UHFFFAOYSA-N 0.000 description 2
- PGKMRRGPTDRTAT-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-7-carbaldehyde Chemical compound C1CCOC2=CC(C=O)=CC=C21 PGKMRRGPTDRTAT-UHFFFAOYSA-N 0.000 description 2
- MUKBOTYAHKQDIM-UHFFFAOYSA-N 3-(3-bromo-6-chloropyridin-2-yl)-2,2-dimethylpropanamide Chemical compound NC(=O)C(C)(C)CC1=NC(Cl)=CC=C1Br MUKBOTYAHKQDIM-UHFFFAOYSA-N 0.000 description 2
- RVTUJABUEWBQDY-UHFFFAOYSA-N 3-(bromomethyl)-8-nitro-2,3-dihydro-1h-imidazo[1,2-a]pyridin-5-one Chemical compound C1=CC(=O)N2C(CBr)CNC2=C1[N+](=O)[O-] RVTUJABUEWBQDY-UHFFFAOYSA-N 0.000 description 2
- YPRMWCKXOZFJGF-UHFFFAOYSA-N 3-bromofuran-2,5-dione Chemical compound BrC1=CC(=O)OC1=O YPRMWCKXOZFJGF-UHFFFAOYSA-N 0.000 description 2
- PVPVPUGHBYWWMK-UHFFFAOYSA-N 3-chloro-6,7-dihydro-[1,4]dioxino[2,3-c]pyridazine Chemical compound O1CCOC2=C1C=C(Cl)N=N2 PVPVPUGHBYWWMK-UHFFFAOYSA-N 0.000 description 2
- RCOQBVRYXNKZGE-UHFFFAOYSA-N 3-ethenyl-6,7-dihydro-[1,4]dioxino[2,3-c]pyridazine Chemical compound O1CCOC2=C1C=C(C=C)N=N2 RCOQBVRYXNKZGE-UHFFFAOYSA-N 0.000 description 2
- VEPGNAIYGRUSIA-UHFFFAOYSA-N 3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde Chemical compound S1CC(=O)NC2=NC(C=O)=CC=C21 VEPGNAIYGRUSIA-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- TWVBMHBWLQNOAM-UHFFFAOYSA-N 4-(2,2-dimethyl-1,3-dioxan-5-yl)-6-methoxy-1,2-dihydropyrido[2,3-b]pyrazin-3-one Chemical compound C12=NC(OC)=CC=C2NCC(=O)N1C1COC(C)(C)OC1 TWVBMHBWLQNOAM-UHFFFAOYSA-N 0.000 description 2
- PHGFCRZYWMZEHJ-UHFFFAOYSA-N 4-(2,2-dimethyl-1,3-dioxan-5-yl)-6-methoxy-3-nitropyridin-2-amine Chemical compound COc1cc(C2COC(C)(C)OC2)c(c(N)n1)[N+]([O-])=O PHGFCRZYWMZEHJ-UHFFFAOYSA-N 0.000 description 2
- ZDXNPYQHRJEQCB-UHFFFAOYSA-N 4-(2,2-dimethyl-1,3-dioxan-5-yl)-6-methoxypyrido[2,3-b]pyrazin-3-one Chemical compound C12=NC(OC)=CC=C2N=CC(=O)N1C1COC(C)(C)OC1 ZDXNPYQHRJEQCB-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- FUSNOPLQVRUIIM-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide Chemical compound O=C1NC(C)(C)CN1C(N=C1N)=NC=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 FUSNOPLQVRUIIM-UHFFFAOYSA-N 0.000 description 2
- SZSMYQPIAAUBBY-UHFFFAOYSA-N 5,6,7,8-tetrahydroisoquinolin-3-ylmethanol Chemical compound C1CCCC2=C1C=C(CO)N=C2 SZSMYQPIAAUBBY-UHFFFAOYSA-N 0.000 description 2
- KWQXWPWIKUNAEO-UHFFFAOYSA-N 5,6,7,8-tetrahydroisoquinoline-3-carbaldehyde Chemical compound C1CCCC2=C1C=C(C=O)N=C2 KWQXWPWIKUNAEO-UHFFFAOYSA-N 0.000 description 2
- DRSLFPHWBGATPA-UHFFFAOYSA-N 5-fluoro-2,3-dihydro-1,4-benzodioxine Chemical compound O1CCOC2=C1C=CC=C2F DRSLFPHWBGATPA-UHFFFAOYSA-N 0.000 description 2
- MSJADAGWGVADGK-UHFFFAOYSA-N 5-fluoro-2,3-dihydro-1,4-benzodioxine-6-carbaldehyde Chemical compound O1CCOC2=C1C=CC(C=O)=C2F MSJADAGWGVADGK-UHFFFAOYSA-N 0.000 description 2
- DQDUXKBVFGPYNO-VOTSOKGWSA-N 6-[(e)-2-phenylethenyl]-[1,2,5]thiadiazolo[3,4-b]pyridine Chemical compound C1=NC2=NSN=C2C=C1\C=C\C1=CC=CC=C1 DQDUXKBVFGPYNO-VOTSOKGWSA-N 0.000 description 2
- QJCKGBXJJJNLKE-UHFFFAOYSA-N 6-bromo-5-fluoro-2,3-dihydro-1,4-benzodioxine Chemical compound O1CCOC2=C1C=CC(Br)=C2F QJCKGBXJJJNLKE-UHFFFAOYSA-N 0.000 description 2
- RDJILYVRVOTMTQ-UHFFFAOYSA-N 6-methoxy-3-nitropyridin-2-amine Chemical compound COC1=CC=C([N+]([O-])=O)C(N)=N1 RDJILYVRVOTMTQ-UHFFFAOYSA-N 0.000 description 2
- AXSGPMJQROKJEE-UHFFFAOYSA-N 7-chloro-3-oxo-4h-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde Chemical compound O1CC(=O)NC2=C1C=C(Cl)C(C=O)=N2 AXSGPMJQROKJEE-UHFFFAOYSA-N 0.000 description 2
- USFWXAHWEZZOEQ-UHFFFAOYSA-N 7-methoxy-1-(oxiran-2-ylmethyl)-3,4-dihydro-1,8-naphthyridin-2-one Chemical compound C12=NC(OC)=CC=C2CCC(=O)N1CC1CO1 USFWXAHWEZZOEQ-UHFFFAOYSA-N 0.000 description 2
- WZWJHPMZAIMHFY-UHFFFAOYSA-N 7-oxo-8h-pyrimido[5,4-b][1,4]thiazine-2-carbaldehyde Chemical compound S1CC(=O)N=C2NC(C=O)=NC=C21 WZWJHPMZAIMHFY-UHFFFAOYSA-N 0.000 description 2
- GXMLDTJVKHBPPM-UHFFFAOYSA-N 8h-pyrimido[5,4-b][1,4]oxazin-7-one Chemical group N1=CN=C2NC(=O)COC2=C1 GXMLDTJVKHBPPM-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 101100365736 Candida albicans (strain SC5314 / ATCC MYA-2876) SEP7 gene Proteins 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 241000400611 Eucalyptus deanei Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 101000965660 Homo sapiens U6 snRNA-associated Sm-like protein LSm8 Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 101100133904 Mus musculus Nrk gene Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- 101150105385 SHS1 gene Proteins 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 102100040948 U6 snRNA-associated Sm-like protein LSm8 Human genes 0.000 description 2
- VTWJKEZCXALLKM-UHFFFAOYSA-N [1,3]oxathiolo[5,4-c]pyridine-6-carbaldehyde Chemical compound C1=NC(C=O)=CC2=C1OCS2 VTWJKEZCXALLKM-UHFFFAOYSA-N 0.000 description 2
- WTLDNGWIWNQNTI-UHFFFAOYSA-N [5-[(4-methoxyphenyl)methoxy]-4-phenylmethoxypyridin-2-yl]methyl acetate Chemical compound C1=CC(OC)=CC=C1COC1=CN=C(COC(C)=O)C=C1OCC1=CC=CC=C1 WTLDNGWIWNQNTI-UHFFFAOYSA-N 0.000 description 2
- 235000010489 acacia gum Nutrition 0.000 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 description 2
- 238000010306 acid treatment Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 230000002365 anti-tubercular Effects 0.000 description 2
- 125000004540 benzothiazol-5-yl group Chemical group S1C=NC2=C1C=CC(=C2)* 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 150000004775 coumarins Chemical class 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012493 hydrazine sulfate Substances 0.000 description 2
- 229910000377 hydrazine sulfate Inorganic materials 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 229960003350 isoniazid Drugs 0.000 description 2
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000006193 liquid solution Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- IBIKHMZPHNKTHM-RDTXWAMCSA-N merck compound 25 Chemical compound C1C[C@@H](C(O)=O)[C@H](O)CN1C(C1=C(F)C=CC=C11)=NN1C(=O)C1=C(Cl)C=CC=C1C1CC1 IBIKHMZPHNKTHM-RDTXWAMCSA-N 0.000 description 2
- 238000003328 mesylation reaction Methods 0.000 description 2
- 238000001465 metallisation Methods 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 229960004738 nicotinyl alcohol Drugs 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000012285 osmium tetroxide Substances 0.000 description 2
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
- GJBCWIOIIAEMHI-UHFFFAOYSA-N oxathiolo[5,4-c]pyridine-6-carbaldehyde Chemical compound O=CN1C=CC2=CSOC2=C1 GJBCWIOIIAEMHI-UHFFFAOYSA-N 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- MXQOYLRVSVOCQT-UHFFFAOYSA-N palladium;tritert-butylphosphane Chemical compound [Pd].CC(C)(C)P(C(C)(C)C)C(C)(C)C.CC(C)(C)P(C(C)(C)C)C(C)(C)C MXQOYLRVSVOCQT-UHFFFAOYSA-N 0.000 description 2
- SCWKRWCUMCMVPW-UHFFFAOYSA-N phenyl n-methylcarbamate Chemical compound CNC(=O)OC1=CC=CC=C1 SCWKRWCUMCMVPW-UHFFFAOYSA-N 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- NSUJAQGRGCFLTI-UHFFFAOYSA-N pyrano[2,3-b]pyridin-2-one Chemical class C1=CN=C2OC(=O)C=CC2=C1 NSUJAQGRGCFLTI-UHFFFAOYSA-N 0.000 description 2
- FNKRSSCRFSZXBE-UHFFFAOYSA-N pyrido[1,2-a]pyrimidin-2-one Chemical class C1=CC=CC2=NC(=O)C=CN21 FNKRSSCRFSZXBE-UHFFFAOYSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- 239000013557 residual solvent Substances 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- FBSPSBREYJKCCL-UHFFFAOYSA-N tert-butyl n-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-n-[1-(1-hydroxy-3-phenylmethoxypropan-2-yl)piperidin-4-yl]carbamate Chemical compound C=1C=2OCCOC=2C=NC=1CN(C(=O)OC(C)(C)C)C(CC1)CCN1C(CO)COCC1=CC=CC=C1 FBSPSBREYJKCCL-UHFFFAOYSA-N 0.000 description 2
- DDAKVOVMPMRCBA-UHFFFAOYSA-N tert-butyl n-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-n-[1-[1-(7-methoxy-2-oxo-3,4-dihydro-1,8-naphthyridin-1-yl)-3-phenylmethoxypropan-2-yl]piperidin-4-yl]carbamate Chemical compound C12=NC(OC)=CC=C2CCC(=O)N1CC(N1CCC(CC1)N(CC=1N=CC=2OCCOC=2C=1)C(=O)OC(C)(C)C)COCC1=CC=CC=C1 DDAKVOVMPMRCBA-UHFFFAOYSA-N 0.000 description 2
- CQIVCHDOPAZLQG-UHFFFAOYSA-N tert-butyl n-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-n-[1-[1-hydroxy-3-(7-methoxy-2-oxo-3,4-dihydro-1,8-naphthyridin-1-yl)propan-2-yl]piperidin-4-yl]carbamate Chemical compound O1CCOC(C=N2)=C1C=C2CN(C(=O)OC(C)(C)C)C(CC1)CCN1C(CO)CN1C(=O)CCC2=CC=C(OC)N=C21 CQIVCHDOPAZLQG-UHFFFAOYSA-N 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- SYSFTTYJTWPOOR-UHFFFAOYSA-N (2-diphenylphosphanyl-1-naphthalen-1-yl-3h-naphthalen-2-yl)-diphenylphosphane Chemical group C1C=C2C=CC=CC2=C(C=2C3=CC=CC=C3C=CC=2)C1(P(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)C1=CC=CC=C1 SYSFTTYJTWPOOR-UHFFFAOYSA-N 0.000 description 1
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- XAYLCFXENJQQLA-UHFFFAOYSA-N (5-tert-butylsulfanyl-4-phenylmethoxypyridin-2-yl)methyl acetate Chemical compound C1=NC(COC(=O)C)=CC(OCC=2C=CC=CC=2)=C1SC(C)(C)C XAYLCFXENJQQLA-UHFFFAOYSA-N 0.000 description 1
- VTLPCULYIMELSM-UHFFFAOYSA-N (7-chloro-3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazin-6-yl)methanol Chemical compound N1CCOC2=C1N=C(CO)C(Cl)=C2 VTLPCULYIMELSM-UHFFFAOYSA-N 0.000 description 1
- XATODVHWQRJWND-UHFFFAOYSA-N (7-chloro-3,4-dihydro-2h-pyrido[3,2-b][1,4]thiazin-6-yl)methanol Chemical compound N1CCSC2=C1N=C(CO)C(Cl)=C2 XATODVHWQRJWND-UHFFFAOYSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- ATWLRNODAYAMQS-UHFFFAOYSA-N 1,1-dibromopropane Chemical compound CCC(Br)Br ATWLRNODAYAMQS-UHFFFAOYSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- VLJMOPCEBPOBBD-UHFFFAOYSA-N 1h-imidazo[4,5-b]pyridine-2-carbaldehyde Chemical compound C1=CC=C2NC(C=O)=NC2=N1 VLJMOPCEBPOBBD-UHFFFAOYSA-N 0.000 description 1
- HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 description 1
- GEFIFDVQYCPLHC-UHFFFAOYSA-N 2,1,3-benzothiadiazole-5-carbaldehyde Chemical compound C1=C(C=O)C=CC2=NSN=C21 GEFIFDVQYCPLHC-UHFFFAOYSA-N 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- UGYVSVVTRQMBST-UHFFFAOYSA-N 2,3-dihydro-[1,4]oxathiino[2,3-c]pyridine-7-carbaldehyde Chemical compound S1CCOC2=C1C=C(C=O)N=C2 UGYVSVVTRQMBST-UHFFFAOYSA-N 0.000 description 1
- MVYWTXXBRDDHSL-UHFFFAOYSA-N 2,3-dihydrofuro[2,3-c]pyridine-5-carbaldehyde Chemical compound C1=NC(C=O)=CC2=C1OCC2 MVYWTXXBRDDHSL-UHFFFAOYSA-N 0.000 description 1
- WBRSYBLNSTYNPP-UHFFFAOYSA-N 2,4,6-tris(ethenyl)-1,3,5,2,4,6-trioxatriborinane Chemical compound C=CB1OB(C=C)OB(C=C)O1 WBRSYBLNSTYNPP-UHFFFAOYSA-N 0.000 description 1
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 1
- ULSHPDVBNUSTIU-UHFFFAOYSA-N 2,6-dihydro-1h-pyridin-3-one Chemical compound O=C1CNCC=C1 ULSHPDVBNUSTIU-UHFFFAOYSA-N 0.000 description 1
- RCTVCSYUAGKSAH-UHFFFAOYSA-N 2-(2,2-dimethyl-1,3-dioxan-5-yl)-6-methoxy-1H-pyridine-2,3-diamine Chemical compound CC1(OCC(CO1)C1(NC(=CC=C1N)OC)N)C RCTVCSYUAGKSAH-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- VAVGOGHLNAJECD-UHFFFAOYSA-N 2-chloro-6-methoxypyridine Chemical compound COC1=CC=CC(Cl)=N1 VAVGOGHLNAJECD-UHFFFAOYSA-N 0.000 description 1
- PMHNOBCGRZJANR-UHFFFAOYSA-N 2-chloro-8h-pyrimido[5,4-b][1,4]thiazin-7-one Chemical compound S1CC(=O)N=C2NC(Cl)=NC=C21 PMHNOBCGRZJANR-UHFFFAOYSA-N 0.000 description 1
- IGXQMWVUAZLBKT-UHFFFAOYSA-N 2-oxochromene-7-carbaldehyde Chemical compound C1=CC(=O)OC2=CC(C=O)=CC=C21 IGXQMWVUAZLBKT-UHFFFAOYSA-N 0.000 description 1
- NXNAKIHVTCYIHY-UHFFFAOYSA-N 2H-1,2-benzoxazine-6-carbaldehyde Chemical compound O1NC=CC2=C1C=CC(=C2)C=O NXNAKIHVTCYIHY-UHFFFAOYSA-N 0.000 description 1
- KMSKJIXHJHFHCO-UHFFFAOYSA-N 2H-1,4-thiazin-6-ylmethanol Chemical compound S1CC=NC=C1CO KMSKJIXHJHFHCO-UHFFFAOYSA-N 0.000 description 1
- RMRLLLIOACRGII-UHFFFAOYSA-N 2h-1,4-benzothiazine-6-carbaldehyde Chemical compound S1CC=NC2=CC(C=O)=CC=C21 RMRLLLIOACRGII-UHFFFAOYSA-N 0.000 description 1
- PVTXJGJDOHYFOX-UHFFFAOYSA-N 2h-1,4-benzoxazine Chemical compound C1=CC=C2N=CCOC2=C1 PVTXJGJDOHYFOX-UHFFFAOYSA-N 0.000 description 1
- GBAOOJAWDCNOGO-UHFFFAOYSA-N 3,4,5-trichloropyridazine Chemical compound ClC1=CN=NC(Cl)=C1Cl GBAOOJAWDCNOGO-UHFFFAOYSA-N 0.000 description 1
- YIHDTNNFJDJYRG-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-6-carbaldehyde Chemical compound O1CCCC2=CC(C=O)=CC=C21 YIHDTNNFJDJYRG-UHFFFAOYSA-N 0.000 description 1
- JCSVFXICFTVFIK-UHFFFAOYSA-N 3,4-dihydro-2h-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde Chemical compound S1CCNC2=NC(C=O)=CC=C21 JCSVFXICFTVFIK-UHFFFAOYSA-N 0.000 description 1
- CFVNJDQTPPEPDC-UHFFFAOYSA-N 3-(6-chloropyridin-2-yl)-2,2-dimethylpropanamide Chemical compound NC(=O)C(C)(C)CC1=CC=CC(Cl)=N1 CFVNJDQTPPEPDC-UHFFFAOYSA-N 0.000 description 1
- DXOSJQLIRGXWCF-UHFFFAOYSA-N 3-fluorocatechol Chemical compound OC1=CC=CC(F)=C1O DXOSJQLIRGXWCF-UHFFFAOYSA-N 0.000 description 1
- VOAJCTMMHSBQGS-UHFFFAOYSA-N 4-(1,3-dihydroxypropan-2-yl)-6-methoxypyrido[2,3-b]pyrazin-3-one Chemical compound N1=CC(=O)N(C(CO)CO)C2=NC(OC)=CC=C21 VOAJCTMMHSBQGS-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- BMASTHFFAMGJKZ-UHFFFAOYSA-N 4-bromo-1,2-dihydropyridazine-3,6-dione Chemical compound BrC1=CC(=O)NNC1=O BMASTHFFAMGJKZ-UHFFFAOYSA-N 0.000 description 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- XJARNPPRUUEDBQ-UHFFFAOYSA-N 4-chloro-7-oxo-8h-pyrimido[5,4-b][1,4]oxazine-2-carbaldehyde Chemical compound O1CC(=O)N=C2NC(C=O)=NC(Cl)=C21 XJARNPPRUUEDBQ-UHFFFAOYSA-N 0.000 description 1
- GGTMKHDQBKQAEP-UHFFFAOYSA-N 4-fluoro-1h-benzimidazole-2-carbaldehyde Chemical compound FC1=CC=CC2=C1N=C(C=O)N2 GGTMKHDQBKQAEP-UHFFFAOYSA-N 0.000 description 1
- OKBNEDPOUYRYNP-UHFFFAOYSA-N 4-methyl-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC(C)(C(O)=O)CC1 OKBNEDPOUYRYNP-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- HRSYWPMGIIAQIW-UHFFFAOYSA-N 5-bromo-2,3-dihydro-1,4-benzodioxine-7-carbaldehyde Chemical compound O1CCOC2=C1C=C(C=O)C=C2Br HRSYWPMGIIAQIW-UHFFFAOYSA-N 0.000 description 1
- LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
- FTDXKGXODWCYBD-UHFFFAOYSA-N 6,7-dihydro-5h-thieno[3,2-b]pyran-2-carbaldehyde Chemical compound O1CCCC2=C1C=C(C=O)S2 FTDXKGXODWCYBD-UHFFFAOYSA-N 0.000 description 1
- CAZNYHXZJYLYJA-UHFFFAOYSA-N 6,7-dihydro-[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde Chemical compound O1CCOC2=C1C=C(C=O)N=N2 CAZNYHXZJYLYJA-UHFFFAOYSA-N 0.000 description 1
- BQWBDYZMUCSEHK-UHFFFAOYSA-N 6-bromo-2,3-dihydro-1-benzofuran Chemical compound BrC1=CC=C2CCOC2=C1 BQWBDYZMUCSEHK-UHFFFAOYSA-N 0.000 description 1
- PNPFLLFIGZXQDJ-UHFFFAOYSA-N 6-bromo-3-(bromomethyl)-8-nitro-2,3-dihydro-1h-imidazo[1,2-a]pyridin-5-one Chemical compound C1=C(Br)C(=O)N2C(CBr)CNC2=C1[N+](=O)[O-] PNPFLLFIGZXQDJ-UHFFFAOYSA-N 0.000 description 1
- YCXWRJNHRLSHIA-UHFFFAOYSA-N 6-bromo-[1,2,5]thiadiazolo[3,4-b]pyridine Chemical compound C1=C(Br)C=NC2=NSN=C21 YCXWRJNHRLSHIA-UHFFFAOYSA-N 0.000 description 1
- OBYJTLDIQBWBHM-UHFFFAOYSA-N 6-chloropyridin-2-amine Chemical compound NC1=CC=CC(Cl)=N1 OBYJTLDIQBWBHM-UHFFFAOYSA-N 0.000 description 1
- RTPVNSMEXOSTED-UHFFFAOYSA-N 7-bromo-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde Chemical compound S1CC(=O)NC2=C1C=C(Br)C(C=O)=N2 RTPVNSMEXOSTED-UHFFFAOYSA-N 0.000 description 1
- LBRCKMYVPVLBPL-UHFFFAOYSA-N 7-chloro-3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde Chemical compound O1CCNC2=C1C=C(Cl)C(C=O)=N2 LBRCKMYVPVLBPL-UHFFFAOYSA-N 0.000 description 1
- OKQHEXJNOMUJGG-UHFFFAOYSA-N 7-chloro-3,4-dihydro-2h-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde Chemical compound S1CCNC2=C1C=C(Cl)C(C=O)=N2 OKQHEXJNOMUJGG-UHFFFAOYSA-N 0.000 description 1
- LNPCPKDZGSQOBD-UHFFFAOYSA-N 7-chloro-3-oxo-4h-1,4-benzoxazine-6-carbaldehyde Chemical compound O1CC(=O)NC2=C1C=C(Cl)C(C=O)=C2 LNPCPKDZGSQOBD-UHFFFAOYSA-N 0.000 description 1
- CVXBIMCUQCZOKY-UHFFFAOYSA-N 7-chloro-3-oxo-4h-pyrido[3,2-b][1,4]thiazine-6-carbaldehyde Chemical compound S1CC(=O)NC2=C1C=C(Cl)C(C=O)=N2 CVXBIMCUQCZOKY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 240000004507 Abelmoschus esculentus Species 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229920000856 Amylose Polymers 0.000 description 1
- 102100029464 Aquaporin-9 Human genes 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- QKIULOOQFIUPAG-UHFFFAOYSA-N CC=CC1(C=CC=CN1)N Chemical compound CC=CC1(C=CC=CN1)N QKIULOOQFIUPAG-UHFFFAOYSA-N 0.000 description 1
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 1
- 108050007331 Cannabinoid receptor Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 101000771413 Homo sapiens Aquaporin-9 Proteins 0.000 description 1
- 101000921370 Homo sapiens Elongation of very long chain fatty acids protein 1 Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229910000909 Lead-bismuth eutectic Inorganic materials 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- IDGQXGPQOGUGIX-VIFPVBQESA-N O-BENZYL-l-SERINE Chemical compound OC(=O)[C@@H](N)COCC1=CC=CC=C1 IDGQXGPQOGUGIX-VIFPVBQESA-N 0.000 description 1
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- VKIJXFIYBAYHOE-VOTSOKGWSA-N [(e)-2-phenylethenyl]boronic acid Chemical compound OB(O)\C=C\C1=CC=CC=C1 VKIJXFIYBAYHOE-VOTSOKGWSA-N 0.000 description 1
- YEYJXUWAPSSGRZ-UHFFFAOYSA-N [1,3]oxathiolo[4,5-c]pyridin-6-ylmethanol Chemical compound C1=NC(CO)=CC2=C1SCO2 YEYJXUWAPSSGRZ-UHFFFAOYSA-N 0.000 description 1
- ACJRTWDNNOGSOO-UHFFFAOYSA-N [4-phenylmethoxy-5-(trifluoromethylsulfonyloxy)pyridin-2-yl]methyl acetate Chemical compound C1=NC(COC(=O)C)=CC(OCC=2C=CC=CC=2)=C1OS(=O)(=O)C(F)(F)F ACJRTWDNNOGSOO-UHFFFAOYSA-N 0.000 description 1
- GOPYZMJAIPBUGX-UHFFFAOYSA-N [O-2].[O-2].[Mn+4] Chemical class [O-2].[O-2].[Mn+4] GOPYZMJAIPBUGX-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical group C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- AXJDEHNQPMZKOS-UHFFFAOYSA-N acetylazanium;chloride Chemical compound [Cl-].CC([NH3+])=O AXJDEHNQPMZKOS-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000005103 alkyl silyl group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- HFEHLDPGIKPNKL-UHFFFAOYSA-N allyl iodide Chemical compound ICC=C HFEHLDPGIKPNKL-UHFFFAOYSA-N 0.000 description 1
- 238000005937 allylation reaction Methods 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 description 1
- GVBAKODNHBJJJO-UHFFFAOYSA-N benzyl 2-methylpropaneperoxoate Chemical compound CC(C(=O)OOCC1=CC=CC=C1)C GVBAKODNHBJJJO-UHFFFAOYSA-N 0.000 description 1
- 239000003781 beta lactamase inhibitor Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229940126813 beta-lactamase inhibitor Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 150000005752 bromopyridines Chemical class 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- STNNHWPJRRODGI-UHFFFAOYSA-N carbonic acid;n,n-diethylethanamine Chemical compound [O-]C([O-])=O.CC[NH+](CC)CC.CC[NH+](CC)CC STNNHWPJRRODGI-UHFFFAOYSA-N 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000004242 cinnolin-3-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)N=NC2=C1[H] 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 0.000 description 1
- QVQGTNFYPJQJNM-UHFFFAOYSA-N dicyclohexylmethanamine Chemical compound C1CCCCC1C(N)C1CCCCC1 QVQGTNFYPJQJNM-UHFFFAOYSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- JMVOCSLPMGHXPG-UHFFFAOYSA-N dipotassium;dioxido(dioxo)osmium Chemical compound [K+].[K+].[O-][Os]([O-])(=O)=O JMVOCSLPMGHXPG-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- DBPFRRFGLYGEJI-UHFFFAOYSA-N ethyl glyoxylate Chemical compound CCOC(=O)C=O DBPFRRFGLYGEJI-UHFFFAOYSA-N 0.000 description 1
- UAYKGOMDUQLCJS-UHFFFAOYSA-N ethylsulfanyl acetate Chemical compound CCSOC(C)=O UAYKGOMDUQLCJS-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical class NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 235000021384 green leafy vegetables Nutrition 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
- 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004551 isoquinolin-3-yl group Chemical group C1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229940095102 methyl benzoate Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
- YPWKLBCTOUEZKE-UHFFFAOYSA-N n-(6-chloropyridin-2-yl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC=CC(Cl)=N1 YPWKLBCTOUEZKE-UHFFFAOYSA-N 0.000 description 1
- KTLGLMQYHZYCCX-UHFFFAOYSA-N n-(6-methoxypyridin-2-yl)propanamide Chemical compound CCC(=O)NC1=CC=CC(OC)=N1 KTLGLMQYHZYCCX-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- XIPFMBOWZXULIA-UHFFFAOYSA-N pivalamide Chemical compound CC(C)(C)C(N)=O XIPFMBOWZXULIA-UHFFFAOYSA-N 0.000 description 1
- 125000005547 pivalate group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical class NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 125000004260 quinazolin-2-yl group Chemical group [H]C1=NC(*)=NC2=C1C([H])=C([H])C([H])=C2[H] 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 1
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- TUZFIWBNGKNFPW-UHFFFAOYSA-M sodium;2-methylpropane-2-thiolate Chemical compound [Na+].CC(C)(C)[S-] TUZFIWBNGKNFPW-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000012607 strong cation exchange resin Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000002278 tabletting lubricant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- XZSNVIWYSJXKQK-UHFFFAOYSA-N tert-butyl n-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-n-piperidin-4-ylcarbamate Chemical compound C=1C=2OCCOC=2C=NC=1CN(C(=O)OC(C)(C)C)C1CCNCC1 XZSNVIWYSJXKQK-UHFFFAOYSA-N 0.000 description 1
- IHVKEOHSLHOWQT-UHFFFAOYSA-N tert-butyl n-[1-[2-hydroxy-3-(7-methoxy-2-oxo-3,4-dihydro-1,8-naphthyridin-1-yl)propyl]piperidin-4-yl]carbamate Chemical compound C12=NC(OC)=CC=C2CCC(=O)N1CC(O)CN1CCC(NC(=O)OC(C)(C)C)CC1 IHVKEOHSLHOWQT-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000017105 transposition Effects 0.000 description 1
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- BWHDROKFUHTORW-UHFFFAOYSA-N tritert-butylphosphane Chemical compound CC(C)(C)P(C(C)(C)C)C(C)(C)C BWHDROKFUHTORW-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- DYNZICQDCVYXFW-AHZSKCOESA-N trovafloxacin mesylate Chemical compound CS(O)(=O)=O.C([C@H]1[C@@H]([C@H]1C1)N)N1C(C(=CC=1C(=O)C(C(O)=O)=C2)F)=NC=1N2C1=CC=C(F)C=C1F DYNZICQDCVYXFW-AHZSKCOESA-N 0.000 description 1
- 229940055820 trovan Drugs 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 150000003952 β-lactams Chemical group 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—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 three hetero rings
- C07D471/16—Peri-condensed systems
-
- 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
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/16—Peri-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0707705A GB0707705D0 (en) | 2007-04-20 | 2007-04-20 | Compounds |
| GB0720569A GB0720569D0 (en) | 2007-10-19 | 2007-10-19 | Compounds |
| GB0805311A GB0805311D0 (en) | 2008-03-20 | 2008-03-20 | Compounds |
| PCT/EP2008/054621 WO2008128942A1 (en) | 2007-04-20 | 2008-04-16 | Tricyclic nitrogen containing compounds as antibacterial agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200970987A1 EA200970987A1 (ru) | 2010-04-30 |
| EA015821B1 true EA015821B1 (ru) | 2011-12-30 |
Family
ID=39580226
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200970987A EA015821B1 (ru) | 2007-04-20 | 2008-04-16 | Трициклические азотсодержащие соединения в качестве антибактериальных агентов |
Country Status (31)
| Country | Link |
|---|---|
| US (1) | US8389524B2 (https=) |
| EP (1) | EP2137196B1 (https=) |
| JP (1) | JP5389013B2 (https=) |
| KR (1) | KR101567096B1 (https=) |
| CN (1) | CN101687887B (https=) |
| AR (1) | AR066111A1 (https=) |
| AT (1) | ATE483717T1 (https=) |
| AU (1) | AU2008240764C1 (https=) |
| BR (1) | BRPI0810064B8 (https=) |
| CA (1) | CA2684659C (https=) |
| CL (1) | CL2008001122A1 (https=) |
| CO (1) | CO6251368A2 (https=) |
| CR (2) | CR11123A (https=) |
| CY (1) | CY1111248T1 (https=) |
| DE (1) | DE602008002912D1 (https=) |
| DK (1) | DK2137196T3 (https=) |
| DO (1) | DOP2009000240A (https=) |
| EA (1) | EA015821B1 (https=) |
| HR (1) | HRP20100574T1 (https=) |
| IL (1) | IL201204A0 (https=) |
| MA (1) | MA31324B1 (https=) |
| MX (1) | MX2009011317A (https=) |
| MY (1) | MY149347A (https=) |
| NZ (1) | NZ579877A (https=) |
| PE (1) | PE20090274A1 (https=) |
| PL (1) | PL2137196T3 (https=) |
| PT (1) | PT2137196E (https=) |
| SI (1) | SI2137196T1 (https=) |
| TW (1) | TWI431006B (https=) |
| UY (1) | UY31038A1 (https=) |
| WO (1) | WO2008128942A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2750935C2 (ru) * | 2016-06-22 | 2021-07-06 | Вандербильт Юниверсити | Положительные аллостерические модуляторы мускаринового ацетилхолинового рецептора m4 |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20080064173A (ko) * | 2005-10-21 | 2008-07-08 | 글락소 그룹 리미티드 | 항균제로서 유용한 페리 축합 트리시클릭 화합물 |
| EP1847543A1 (de) | 2006-04-19 | 2007-10-24 | Boehringer Ingelheim Pharma GmbH & Co. KG | Dihydrothienopyrimidine zur Behandlung von entzündlichen Erkrankungen |
| GB0608263D0 (en) | 2006-04-26 | 2006-06-07 | Glaxo Group Ltd | Compounds |
| AU2008313660B2 (en) | 2007-10-19 | 2013-11-07 | Boehringer Ingelheim International Gmbh | Substituted piperidino-dihydrothienopyrimidines |
| EP2205609B1 (de) | 2007-10-19 | 2017-03-29 | Boehringer Ingelheim International GmbH | Heterocyclus-substituierte piperazino-dihydrothienopyrimidine |
| WO2009050236A1 (de) | 2007-10-19 | 2009-04-23 | Boehringer Ingelheim International Gmbh | Neue piperazino-dihydrothienopyrimidin-derivate |
| ES2411930T3 (es) | 2008-02-20 | 2013-07-09 | Actelion Pharmaceuticals Ltd. | Compuestos antibióticos azatricíclicos |
| JP2011520944A (ja) * | 2008-05-23 | 2011-07-21 | グラクソ グループ リミテッド | 窒素含有三環式化合物および抗菌剤としてのその使用 |
| BRPI0912995A2 (pt) * | 2008-05-23 | 2015-10-13 | Glaxo Group Ltd | compostos tricíclicos contendo nitrogênio e sua utilização como agentes antibacterianos |
| BRPI0920895A8 (pt) | 2008-10-07 | 2017-12-26 | Actelion Pharmaceuticals Ltd | Compostos antibióticos de oxazolidinona tricíclica |
| WO2010043714A1 (en) | 2008-10-17 | 2010-04-22 | Glaxo Group Limited | Tricyclic nitrogen compounds used as antibacterials |
| CA2749163A1 (en) | 2009-01-14 | 2010-07-22 | The Salk Institute For Biological Studies | Methods for screening and compounds that protect against amyloid diseases |
| AR076222A1 (es) | 2009-04-09 | 2011-05-26 | Actelion Pharmaceuticals Ltd | Derivados 2-hidroxietil-1h-quinolin-ona y sus analogos azaisotericos con actividad antibacteriana y composiciones farmaceuticas que los contienen |
| TW201130854A (en) | 2009-12-22 | 2011-09-16 | Bayer Schering Pharma Ag | Pyridinone derivatives and pharmaceutical compositions thereof |
| CA2797708C (en) * | 2010-05-04 | 2016-08-16 | Alkermes Pharma Ireland Limited | Process for synthesizing oxidized lactam compounds |
| US20130059866A1 (en) | 2011-08-24 | 2013-03-07 | Boehringer Ingelheim International Gmbh | Novel piperidino-dihydrothienopyrimidine sulfoxides and their use for treating copd and asthma |
| US9802954B2 (en) | 2011-08-24 | 2017-10-31 | Boehringer Ingelheim International Gmbh | Piperidino-dihydrothienopyrimidine sulfoxides and their use for treating COPD and asthma |
| CN103113291B (zh) * | 2013-02-04 | 2015-03-04 | 浙江大学 | 一种3位烯基吡啶衍生物的合成方法 |
| JP6453216B2 (ja) * | 2013-07-23 | 2019-01-16 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ヘテロ縮合環化合物 |
| JP6546654B2 (ja) | 2014-08-22 | 2019-07-17 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | 淋菌感染を治療するための三環式含窒素化合物 |
| WO2018195098A1 (en) | 2017-04-17 | 2018-10-25 | Ohio State Innovation Foundation | Type ii topoisomerase inhibitors and methods of making and using thereof |
| WO2020201833A1 (en) | 2019-04-03 | 2020-10-08 | Glaxomithkline Intellectual Property Development Limited | Gepotidacin for use in the treatment of bacterial urinary tract infections |
| CN114173789A (zh) * | 2019-07-05 | 2022-03-11 | 葛兰素史克知识产权发展有限公司 | 用于治疗由生殖支原体引起的感染的组合 |
| ES3004932T3 (en) | 2020-04-02 | 2025-03-13 | Glaxosmithkline Ip Dev Ltd | Regimen for treating a neisseria gonorrhoeae infection with gepotidacin |
| EP4143188A1 (en) * | 2020-04-29 | 2023-03-08 | GlaxoSmithKline Intellectual Property Development Limited | Crystalline forms of gepotidacin |
| CN111494241B (zh) * | 2020-06-01 | 2023-03-24 | 湖北洁世达环保科技有限公司 | 一种纸巾柔润保湿液 |
| CA3210313A1 (en) * | 2021-02-05 | 2022-08-11 | Glaxosmithkline Intellectual Property Development Limited | Oral solid dose formulations |
| US20250099535A1 (en) | 2022-01-21 | 2025-03-27 | Glaxosmithkline Intellectual Property Development Limited | Gepotidacin and vancomycin for use in the treatment of an infection caused by staphylococcus saprophyticus |
| EP4316463A1 (en) | 2022-08-02 | 2024-02-07 | GlaxoSmithKline Intellectual Property Development Limited | Novel formulation |
| CN119546302A (zh) | 2022-09-26 | 2025-02-28 | 葛兰素史密斯克莱知识产权发展有限公司 | 用于治疗细菌性前列腺炎的吉泊达星 |
| CN121537412B (zh) * | 2026-01-16 | 2026-04-03 | 南京道尔医药研究院有限公司 | 一种吉泊达星甲磺酸盐的制备方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002004445A1 (en) * | 2000-07-12 | 2002-01-17 | Pharmacia & Upjohn Company | Heterocycle carboxamides as antiviral agents |
| WO2004002490A2 (en) * | 2002-06-26 | 2004-01-08 | Glaxo Group Limited | Piperidine compounds as antibacterials |
| WO2007081597A2 (en) * | 2005-10-21 | 2007-07-19 | Glaxo Group Limited | Peri condensed tricyclic compounds useful as antibacterial agents |
| WO2007122258A1 (en) * | 2006-04-26 | 2007-11-01 | Glaxo Group Limited | Tryclic nitrogen containing compounds and their use as antibacterials |
| EP1900732A1 (en) * | 2005-06-24 | 2008-03-19 | Toyama Chemical Co., Ltd. | Novel nitrogenated heterocyclic compound and salt thereof |
Family Cites Families (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6403610B1 (en) | 1999-09-17 | 2002-06-11 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation and the compositions which comprise them |
| US6525049B2 (en) | 2000-07-05 | 2003-02-25 | Pharmacia & Upjohn Company | Pyrroloquinolones as antiviral agents |
| CZ2003243A3 (cs) | 2000-07-26 | 2003-09-17 | Smithkline Beecham P. L. C. | Aminopiperidinové chinoliny a jejich azaisosterické analogy s antibakteriální aktivitou |
| US6603005B2 (en) | 2000-11-15 | 2003-08-05 | Aventis Pharma S.A. | Heterocyclylalkylpiperidine derivatives, their preparation and compositions containing them |
| GB0031088D0 (en) | 2000-12-20 | 2001-01-31 | Smithkline Beecham Plc | Medicaments |
| EP1345903A1 (en) | 2000-12-21 | 2003-09-24 | Ciba SC Holding AG | Crystalline forms of cerivastatin sodium |
| GB0101577D0 (en) | 2001-01-22 | 2001-03-07 | Smithkline Beecham Plc | Compounds |
| US6602884B2 (en) | 2001-03-13 | 2003-08-05 | Aventis Pharma S.A. | Quinolylpropylpiperidine derivatives, their preparation, and compositions containing them |
| GB0112834D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0112836D0 (en) | 2001-05-25 | 2001-07-18 | Smithkline Beecham Plc | Medicaments |
| GB0118238D0 (en) | 2001-07-26 | 2001-09-19 | Smithkline Beecham Plc | Medicaments |
| AU2002350217A1 (en) | 2001-12-04 | 2003-06-17 | Bristol-Myers Squibb Company | Glycinamides as factor xa inhibitors |
| WO2003064431A2 (en) | 2002-01-29 | 2003-08-07 | Glaxo Group Limited | Aminopiperidine compounds, process for their preparation, and pharmaceutical compositions containing them |
| EP1470125A1 (en) | 2002-01-29 | 2004-10-27 | Glaxo Group Limited | Aminopiperidine derivatives |
| TW200406413A (en) | 2002-06-26 | 2004-05-01 | Glaxo Group Ltd | Compounds |
| GB0217294D0 (en) | 2002-07-25 | 2002-09-04 | Glaxo Group Ltd | Medicaments |
| FR2844270B1 (fr) | 2002-09-11 | 2006-05-19 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leur procede et intermediaires de preparation et les compositions qui les contiennent |
| FR2844268B1 (fr) | 2002-09-11 | 2004-10-22 | Aventis Pharma Sa | Derives de la quinolyl propyl piperidine, leurs procedes et intermediaires de preparation et les compositions qui les contiennent |
| WO2004035569A2 (de) | 2002-10-10 | 2004-04-29 | Morphochem Aktiengesellschaft für kombinatorische Chemie | Neue verbindungen mit antibakterieller aktivität |
| DE60331849D1 (de) | 2002-11-05 | 2010-05-06 | Glaxosmithkline Llc | Antibakterielle wirkstoffe |
| ATE479683T1 (de) | 2002-11-05 | 2010-09-15 | Glaxo Group Ltd | Antibakterielle mittel |
| TW200427688A (en) | 2002-12-18 | 2004-12-16 | Glaxo Group Ltd | Antibacterial agents |
| TW200507841A (en) | 2003-03-27 | 2005-03-01 | Glaxo Group Ltd | Antibacterial agents |
| US7232833B2 (en) | 2003-03-28 | 2007-06-19 | Novexel | 4-substituted quinoline derivatives, method and intermediates for their preparation and pharmaceutical compositions containing them |
| DE10316081A1 (de) | 2003-04-08 | 2004-10-21 | Morphochem AG Aktiengesellschaft für kombinatorische Chemie | Neue Verbindungen mit antibakterieller Aktivität |
| US7348434B2 (en) | 2003-08-08 | 2008-03-25 | Antony Bigot | 4-substituted quinoline derivatives, method and intermediates for their preparation and pharmaceutical compositions containing them |
| FR2867472B1 (fr) | 2004-03-12 | 2008-07-18 | Aventis Pharma Sa | Derives de quinoleines-4-substituees, leurs procede et intermediaires de preparation et les compositions pharmaceutiques qui les contiennent |
| US7691850B2 (en) | 2004-06-15 | 2010-04-06 | Glaxo Group Limited | Antibacterial agents |
| FR2872164B1 (fr) | 2004-06-29 | 2006-11-17 | Aventis Pharma Sa | Derives de quinoleines-4-substituees, leur procede et intermediaires de preparation et les compositions pharmaceutiques qui les contiennent |
| US20070254872A1 (en) | 2004-07-08 | 2007-11-01 | Glaxo Group Limited | Antibacterial Agents |
| US20080194547A1 (en) | 2004-07-09 | 2008-08-14 | Glaxo Group Limited | Antibacterial Agents |
| US7648984B2 (en) | 2004-07-13 | 2010-01-19 | Glaxo Group Limited | Antibacterial agents |
| US20070270417A1 (en) | 2004-07-22 | 2007-11-22 | Glaxo Group Limited | Antibacterial Agents |
| US7655648B2 (en) | 2004-08-02 | 2010-02-02 | Glaxo Group Limited | Antibacterial agents |
| US20070161627A1 (en) | 2004-08-09 | 2007-07-12 | Miller William H | Antibacterial agents |
| DE102004041163A1 (de) | 2004-08-25 | 2006-03-02 | Morphochem Aktiengesellschaft für kombinatorische Chemie | Neue Verbindungen mit antibakterieller Aktivität |
| CA2580621A1 (en) | 2004-09-24 | 2006-03-30 | Actelion Pharmaceuticals Ltd | New bicyclic antibiotics |
| WO2006038172A1 (en) | 2004-10-05 | 2006-04-13 | Actelion Pharmaceuticals Ltd | New piperidine antibiotics |
| JP5314244B2 (ja) | 2004-10-27 | 2013-10-16 | 富山化学工業株式会社 | 新規な含窒素複素環化合物およびその塩 |
| EP1846418A4 (en) | 2005-01-25 | 2009-12-23 | Glaxo Group Ltd | ANTIBACTERIAL ACTIVE SUBSTANCES |
| JP2008528598A (ja) | 2005-01-25 | 2008-07-31 | グラクソ グループ リミテッド | 抗菌剤 |
| US7709472B2 (en) | 2005-01-25 | 2010-05-04 | Glaxo Group Limited | Antibacterial agents |
| US7648980B2 (en) | 2005-01-25 | 2010-01-19 | Glaxo Group Limited | Antibacterial agents |
| JP2008528604A (ja) | 2005-01-25 | 2008-07-31 | グラクソ グループ リミテッド | 抗菌剤 |
| WO2006099884A1 (en) | 2005-03-24 | 2006-09-28 | Actelion Percurex Ag | Beta-aminoalcohol antibiotics |
| NZ562034A (en) | 2005-03-31 | 2009-10-30 | Janssen Pharmaceutica Nv | Bicyclic pyrazole compounds as antibacterial agents |
| EP1891078A1 (en) | 2005-05-24 | 2008-02-27 | AstraZeneca AB | Aminopiperidine quinolines and their azaisosteric analogues with antibacterial activity |
| WO2006126171A2 (en) | 2005-05-25 | 2006-11-30 | Actelion Pharmaceuticals Ltd | New antibiotic derivatives |
| MY150958A (en) | 2005-06-16 | 2014-03-31 | Astrazeneca Ab | Compounds for the treatment of multi-drug resistant bacterial infections |
| ATE465163T1 (de) | 2005-12-22 | 2010-05-15 | Glaxo Group Ltd | Heterocyclische verbindungen, ihre herstellung und ihre verwendung als antibakterielle mittel |
| WO2007115947A1 (en) | 2006-04-06 | 2007-10-18 | Glaxo Group Limited | Pyrrolo-quinoxalinone derivatives as antibacterials |
| EP2007377A4 (en) | 2006-04-06 | 2011-08-17 | Glaxo Group Ltd | ANTIBACTERIAL ACTIVE SUBSTANCES |
| US20100256124A1 (en) | 2006-06-09 | 2010-10-07 | David Thomas Davies | Substituted 1-Methyl-1H-Quinolin-2-Ones And 1-Methyl-1H-1,5-Naphthyridin-2-Ones As Antibacterials |
| GB0613208D0 (en) | 2006-07-03 | 2006-08-09 | Glaxo Group Ltd | Compounds |
| EP1992628A1 (en) | 2007-05-18 | 2008-11-19 | Glaxo Group Limited | Derivatives and analogs of N-ethylquinolones and N-ethylazaquinolones |
| GB0705672D0 (en) * | 2007-03-23 | 2007-05-02 | Glaxo Group Ltd | Compounds |
| EP1980251A1 (en) | 2007-04-13 | 2008-10-15 | Glaxo Group Limited | Pyrrolo[3,2,1-ij]quinoline-4-one derivatives for treating tuberculosis |
| GB0707706D0 (en) | 2007-04-20 | 2007-05-30 | Glaxo Group Ltd | Compounds |
| GB0707708D0 (en) | 2007-04-20 | 2007-05-30 | Glaxo Group Ltd | Compounds |
| EP2005995A1 (en) | 2007-06-22 | 2008-12-24 | Glaxo Group Limited | Heterocyclic compounds for the treatment of tuberculosis |
| GB0800367D0 (en) | 2008-01-09 | 2008-02-20 | Glaxo Group Ltd | Compounds |
-
2008
- 2008-04-16 EA EA200970987A patent/EA015821B1/ru not_active IP Right Cessation
- 2008-04-16 US US12/596,685 patent/US8389524B2/en active Active
- 2008-04-16 HR HR20100574T patent/HRP20100574T1/hr unknown
- 2008-04-16 WO PCT/EP2008/054621 patent/WO2008128942A1/en not_active Ceased
- 2008-04-16 KR KR1020097024090A patent/KR101567096B1/ko active Active
- 2008-04-16 PT PT08749580T patent/PT2137196E/pt unknown
- 2008-04-16 CN CN2008800213034A patent/CN101687887B/zh active Active
- 2008-04-16 AT AT08749580T patent/ATE483717T1/de active
- 2008-04-16 EP EP08749580A patent/EP2137196B1/en active Active
- 2008-04-16 MX MX2009011317A patent/MX2009011317A/es active IP Right Grant
- 2008-04-16 AU AU2008240764A patent/AU2008240764C1/en active Active
- 2008-04-16 CA CA2684659A patent/CA2684659C/en active Active
- 2008-04-16 NZ NZ579877A patent/NZ579877A/en unknown
- 2008-04-16 DE DE602008002912T patent/DE602008002912D1/de active Active
- 2008-04-16 BR BRPI0810064A patent/BRPI0810064B8/pt active IP Right Grant
- 2008-04-16 JP JP2010503491A patent/JP5389013B2/ja active Active
- 2008-04-16 PL PL08749580T patent/PL2137196T3/pl unknown
- 2008-04-16 MY MYPI20094376A patent/MY149347A/en unknown
- 2008-04-16 DK DK08749580.0T patent/DK2137196T3/da active
- 2008-04-16 SI SI200830103T patent/SI2137196T1/sl unknown
- 2008-04-18 AR ARP080101605A patent/AR066111A1/es active IP Right Grant
- 2008-04-18 PE PE2008000682A patent/PE20090274A1/es active IP Right Grant
- 2008-04-18 CL CL200801122A patent/CL2008001122A1/es unknown
- 2008-04-18 UY UY31038A patent/UY31038A1/es active IP Right Grant
- 2008-04-18 TW TW097114042A patent/TWI431006B/zh active
-
2009
- 2009-09-24 IL IL201204A patent/IL201204A0/en active IP Right Grant
- 2009-10-09 DO DO2009000240A patent/DOP2009000240A/es unknown
- 2009-10-19 CO CO09116570A patent/CO6251368A2/es not_active Application Discontinuation
- 2009-10-21 MA MA32296A patent/MA31324B1/fr unknown
- 2009-11-20 CR CR11123A patent/CR11123A/es unknown
-
2010
- 2010-11-24 CY CY20101101052T patent/CY1111248T1/el unknown
-
2015
- 2015-10-23 CR CR20150586A patent/CR20150586A/es unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002004445A1 (en) * | 2000-07-12 | 2002-01-17 | Pharmacia & Upjohn Company | Heterocycle carboxamides as antiviral agents |
| WO2004002490A2 (en) * | 2002-06-26 | 2004-01-08 | Glaxo Group Limited | Piperidine compounds as antibacterials |
| EP1900732A1 (en) * | 2005-06-24 | 2008-03-19 | Toyama Chemical Co., Ltd. | Novel nitrogenated heterocyclic compound and salt thereof |
| WO2007081597A2 (en) * | 2005-10-21 | 2007-07-19 | Glaxo Group Limited | Peri condensed tricyclic compounds useful as antibacterial agents |
| WO2007122258A1 (en) * | 2006-04-26 | 2007-11-01 | Glaxo Group Limited | Tryclic nitrogen containing compounds and their use as antibacterials |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2750935C2 (ru) * | 2016-06-22 | 2021-07-06 | Вандербильт Юниверсити | Положительные аллостерические модуляторы мускаринового ацетилхолинового рецептора m4 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11229646B2 (en) | Method for treating gonorrhea with (2R)-2-({4-[(3,4-dihydro-2H-pyrano[2,3-C]pyridin-6-ylmethyl)amino]-1-piperidinyl}methyl)-1,2-dihydro-3H,8H-2A,5,8A-triazaacenaphthylene-3,8-dione | |
| JP5389013B2 (ja) | 抗菌剤としての三環式含窒素化合物 | |
| EP2136807A1 (en) | Pyrrolo (3, 2, 1-ij) quinoline-4-one derivatives for treating tuberculosis | |
| JP2010524887A (ja) | 抗菌剤としての含窒素三環式複素環化合物 | |
| US20100184751A1 (en) | Heterocyclic compounds for the treatment of tuberculosis | |
| US20110009394A1 (en) | Tricyclic nitrogen compounds and their use as antibacterial agents | |
| US20110275661A1 (en) | Tricyclic nitrogen compounds used as antibacterials | |
| ES2351377T3 (es) | Compuestos tricíclicos que contienen nitrógeno como agentes antibacterianos. | |
| HK1138000B (en) | Tricyclic nitrogen containing compounds as antibacterial agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM KG TM |