UA118868C2 - ПОХІДНІ 1,2-ДИГІДРО-3H-ПІРОЛО[1,2-c]ІМІДАЗОЛ-3-ОНУ ТА ЇХ ЗАСТОСУВАННЯ ЯК АНТИБАКТЕРІАЛЬНИХ ЗАСОБІВ - Google Patents

Info

Publication number

UA118868C2

UA118868C2 UAA201609996A UAA201609996A UA118868C2 UA 118868 C2 UA118868 C2 UA 118868C2 UA A201609996 A UAA201609996 A UA A201609996A UA A201609996 A UAA201609996 A UA A201609996A UA 118868 C2 UA118868 C2 UA 118868C2

Authority

UA

Ukraine

Prior art keywords

methyl

hydroxy

pyrrolo

methylsulfonyl

oxo

Prior art date

2014-03-04

Links

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• 239000003242 anti bacterial agent Substances 0.000 title description 13
• XTYMYZJHPHOJAW-UHFFFAOYSA-N 1,2-dihydropyrrolo[1,2-c]imidazol-3-one Chemical class C1=CN2C(=O)NCC2=C1 XTYMYZJHPHOJAW-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 617
• 150000003839 salts Chemical class 0.000 claims abstract description 70
• -1 1,2-dihydroxyethyl Chemical group 0.000 claims description 448
• 125000000217 alkyl group Chemical group 0.000 claims description 77
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 73
• 229910052736 halogen Inorganic materials 0.000 claims description 46
• 150000002367 halogens Chemical class 0.000 claims description 45
• 125000003545 alkoxy group Chemical group 0.000 claims description 44
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 43
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 38
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 30
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 30
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
• 208000035143 Bacterial infection Diseases 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 26
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 25
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 22
• 239000011737 fluorine Substances 0.000 claims description 22
• 229910052731 fluorine Inorganic materials 0.000 claims description 22
• 230000002265 prevention Effects 0.000 claims description 20
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 19
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 19
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 17
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 17
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 9
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 9
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 5
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
• 150000002460 imidazoles Chemical class 0.000 claims description 4
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 125000004001 thioalkyl group Chemical group 0.000 claims description 3
• PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical compound NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-UHFFFAOYSA-N 0.000 claims description 2
• 239000000945 filler Substances 0.000 claims description 2
• 208000027096 gram-negative bacterial infections Diseases 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 15
• DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 4
• JHAYEQICABJSTP-UHFFFAOYSA-N decoquinate Chemical group N1C=C(C(=O)OCC)C(=O)C2=C1C=C(OCC)C(OCCCCCCCCCC)=C2 JHAYEQICABJSTP-UHFFFAOYSA-N 0.000 claims 1
• 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims 1
• FBTNXKPMTVSCRR-UHFFFAOYSA-N n-methylsulfonylbutanamide Chemical compound CCCC(=O)NS(C)(=O)=O FBTNXKPMTVSCRR-UHFFFAOYSA-N 0.000 claims 1
• 230000000844 anti-bacterial effect Effects 0.000 abstract description 15
• 230000015572 biosynthetic process Effects 0.000 description 416
• 238000003786 synthesis reaction Methods 0.000 description 413
• 238000000034 method Methods 0.000 description 276
• 238000005481 NMR spectroscopy Methods 0.000 description 167
• 239000007787 solid Substances 0.000 description 145
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 132
• 239000000203 mixture Substances 0.000 description 122
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 108
• 238000000746 purification Methods 0.000 description 97
• 239000000243 solution Substances 0.000 description 94
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
• 238000006243 chemical reaction Methods 0.000 description 78
• 239000010410 layer Substances 0.000 description 78
• 239000011541 reaction mixture Substances 0.000 description 76
• 239000000543 intermediate Substances 0.000 description 74
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 71
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 64
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
• 229910052740 iodine Inorganic materials 0.000 description 44
• 238000005160 1H NMR spectroscopy Methods 0.000 description 41
• 241000894006 Bacteria Species 0.000 description 41
• 239000012230 colorless oil Substances 0.000 description 38
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 35
• 239000002904 solvent Substances 0.000 description 34
• 241000905957 Channa melasoma Species 0.000 description 33
• 229910052770 Uranium Inorganic materials 0.000 description 32
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 239000000706 filtrate Substances 0.000 description 31
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 30
• 208000015181 infectious disease Diseases 0.000 description 27
• 239000003921 oil Substances 0.000 description 27
• 235000019198 oils Nutrition 0.000 description 27
• 239000012071 phase Substances 0.000 description 23
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• HJZVHUQSQGITAM-UHFFFAOYSA-N butanamide Chemical compound CC[CH]C(N)=O HJZVHUQSQGITAM-UHFFFAOYSA-N 0.000 description 21
• 125000004432 carbon atom Chemical group C* 0.000 description 21
• 230000002829 reductive effect Effects 0.000 description 21
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
• 239000003480 eluent Substances 0.000 description 16
• 239000000725 suspension Substances 0.000 description 16
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 15
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 15
• 229910052794 bromium Inorganic materials 0.000 description 15
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
• 239000000126 substance Substances 0.000 description 15
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 14
• 239000002253 acid Substances 0.000 description 14
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 13
• 239000002585 base Chemical class 0.000 description 13
• 239000006260 foam Substances 0.000 description 13
• 238000007429 general method Methods 0.000 description 13
• 239000011630 iodine Substances 0.000 description 13
• 239000011780 sodium chloride Substances 0.000 description 13
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
• 230000000052 comparative effect Effects 0.000 description 12
• 230000014759 maintenance of location Effects 0.000 description 12
• 238000002360 preparation method Methods 0.000 description 12
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
• 238000001556 precipitation Methods 0.000 description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
• 229910052757 nitrogen Inorganic materials 0.000 description 10
• 239000012044 organic layer Substances 0.000 description 10
• 229910052727 yttrium Inorganic materials 0.000 description 10
• 125000000623 heterocyclic group Chemical group 0.000 description 9
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 9
• 239000000047 product Substances 0.000 description 9
• LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 8
• 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 8
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
• 108091034117 Oligonucleotide Proteins 0.000 description 8
• 229940088710 antibiotic agent Drugs 0.000 description 8
• 125000003118 aryl group Chemical group 0.000 description 8
• VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 description 8
• 229910052739 hydrogen Inorganic materials 0.000 description 8
• 125000002768 hydroxyalkyl group Chemical group 0.000 description 8
• 229940126601 medicinal product Drugs 0.000 description 8
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 7
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 238000001035 drying Methods 0.000 description 7
• 239000001257 hydrogen Substances 0.000 description 7
• 238000010561 standard procedure Methods 0.000 description 7
• 238000000825 ultraviolet detection Methods 0.000 description 7
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 6
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 150000001345 alkine derivatives Chemical class 0.000 description 6
• 239000007795 chemical reaction product Substances 0.000 description 6
• MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 6
• 125000000753 cycloalkyl group Chemical group 0.000 description 6
• 238000001514 detection method Methods 0.000 description 6
• 229940079593 drug Drugs 0.000 description 6
• 238000010828 elution Methods 0.000 description 6
• 125000001072 heteroaryl group Chemical group 0.000 description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 6
• GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• 125000006239 protecting group Chemical group 0.000 description 6
• 238000000926 separation method Methods 0.000 description 6
• 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• 235000010469 Glycine max Nutrition 0.000 description 5
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 125000004103 aminoalkyl group Chemical group 0.000 description 5
• 230000003115 biocidal effect Effects 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 239000000460 chlorine Substances 0.000 description 5
• 229910052801 chlorine Inorganic materials 0.000 description 5
• 239000010949 copper Substances 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 235000019253 formic acid Nutrition 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• 239000002480 mineral oil Substances 0.000 description 5
• 235000010446 mineral oil Nutrition 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• 239000012299 nitrogen atmosphere Substances 0.000 description 5
• 238000004809 thin layer chromatography Methods 0.000 description 5
• 125000005309 thioalkoxy group Chemical group 0.000 description 5
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 4
• 229930186147 Cephalosporin Natural products 0.000 description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
• 229910019142 PO4 Inorganic materials 0.000 description 4
• 101150024701 PPH3 gene Proteins 0.000 description 4
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 4
• 239000000538 analytical sample Substances 0.000 description 4
• 229910052786 argon Inorganic materials 0.000 description 4
• 239000012298 atmosphere Substances 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• 102000006635 beta-lactamase Human genes 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 229940124587 cephalosporin Drugs 0.000 description 4
• 150000001780 cephalosporins Chemical class 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 239000012043 crude product Substances 0.000 description 4
• 230000001419 dependent effect Effects 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 238000004108 freeze drying Methods 0.000 description 4
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
• 150000002923 oximes Chemical class 0.000 description 4
• HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
• 239000010452 phosphate Substances 0.000 description 4
• ZSKGQVFRTSEPJT-UHFFFAOYSA-N pyrrole-2-carboxaldehyde Chemical class O=CC1=CC=CN1 ZSKGQVFRTSEPJT-UHFFFAOYSA-N 0.000 description 4
• 238000006268 reductive amination reaction Methods 0.000 description 4
• 229920006395 saturated elastomer Polymers 0.000 description 4
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 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
• 238000001665 trituration Methods 0.000 description 4
• 208000019206 urinary tract infection Diseases 0.000 description 4
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 3
• BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical compound OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 3
• BFLZAGBPYBMKLS-UHFFFAOYSA-N 2-methylsulfonylbutanoic acid Chemical compound CCC(C(O)=O)S(C)(=O)=O BFLZAGBPYBMKLS-UHFFFAOYSA-N 0.000 description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
• AEYJSULNKPFTAP-UHFFFAOYSA-N 4-iodo-1h-pyrrole-2-carbaldehyde Chemical compound IC1=CNC(C=O)=C1 AEYJSULNKPFTAP-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
• 201000003883 Cystic fibrosis Diseases 0.000 description 3
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
• 108090000204 Dipeptidase 1 Proteins 0.000 description 3
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
• 241000282414 Homo sapiens Species 0.000 description 3
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
• 208000032376 Lung infection Diseases 0.000 description 3
• QJEBZRZHCVTKSX-UHFFFAOYSA-N OCCN1C(N(CC1)C1=CC=C(C=C1)I)=O Chemical compound OCCN1C(N(CC1)C1=CC=C(C=C1)I)=O QJEBZRZHCVTKSX-UHFFFAOYSA-N 0.000 description 3
• 235000019502 Orange oil Nutrition 0.000 description 3
• 229930182555 Penicillin Natural products 0.000 description 3
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 125000004414 alkyl thio group Chemical group 0.000 description 3
• 150000001408 amides Chemical class 0.000 description 3
• 230000001580 bacterial effect Effects 0.000 description 3
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