SK5982003A3 - 1-Methylcarbapenem derivatives - Google Patents

Info

Publication number

SK5982003A3

SK5982003A3 SK598-2003A SK5982003A SK5982003A3 SK 5982003 A3 SK5982003 A3 SK 5982003A3 SK 5982003 A SK5982003 A SK 5982003A SK 5982003 A3 SK5982003 A3 SK 5982003A3

Authority

SK

Slovakia

Prior art keywords

group

azetidin

thio

hydroxyethyl

carboxylic acid

Prior art date

2000-11-16

Links

• Espacenet
• Global Dossier
• Discuss

• YKMONJZIUAOVEM-GDVGLLTNSA-N (5S)-4-methyl-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class CC1C=CN2[C@H]1CC2=O YKMONJZIUAOVEM-GDVGLLTNSA-N 0.000 title abstract description 9
• 150000001875 compounds Chemical class 0.000 claims abstract description 345
• 150000003839 salts Chemical class 0.000 claims abstract description 67
• 150000002148 esters Chemical class 0.000 claims abstract description 61
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 22
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 20
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
• 125000004434 sulfur atom Chemical group 0.000 claims abstract description 11
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 6
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 4
• 239000004480 active ingredient Substances 0.000 claims abstract description 3
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract 5
• -1 1-methylcarbapenem compound Chemical class 0.000 claims description 355
• 239000000203 mixture Substances 0.000 claims description 223
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 165
• 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 139
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 86
• 229910052739 hydrogen Inorganic materials 0.000 claims description 77
• 125000001424 substituent group Chemical group 0.000 claims description 69
• 239000001257 hydrogen Substances 0.000 claims description 44
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 38
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 35
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
• 125000003277 amino group Chemical group 0.000 claims description 23
• 150000002431 hydrogen Chemical class 0.000 claims description 20
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
• 229910052760 oxygen Chemical group 0.000 claims description 19
• 239000001301 oxygen Chemical group 0.000 claims description 19
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 18
• 125000000217 alkyl group Chemical group 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 12
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
• 239000000460 chlorine Substances 0.000 claims description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
• 239000011593 sulfur Substances 0.000 claims description 11
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 8
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 8
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 8
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 125000000623 heterocyclic group Chemical group 0.000 claims description 7
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
• 125000002393 azetidinyl group Chemical group 0.000 claims description 6
• 229910052801 chlorine Inorganic materials 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 4
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
• 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 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 4
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
• 229910052799 carbon Inorganic materials 0.000 claims description 3
• QQVUUJNSDZWJLM-KAILVDNBSA-N (4r,5s,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-3-[1-[4-[[(3r)-pyrrolidin-3-yl]carbamoyl]-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)SC(C1)CN1C(SC=1)=NC=1C(=O)N[C@@H]1CCNC1 QQVUUJNSDZWJLM-KAILVDNBSA-N 0.000 claims description 2
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
• KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical group O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 3
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims 2
• KJTDZYVBJUOGJB-GAJNKVMBSA-N (4r,5s,6s)-3-[1-[4-(aminomethyl)-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)SC(C1)CN1C1=NC(CN)=CS1 KJTDZYVBJUOGJB-GAJNKVMBSA-N 0.000 claims 1
• QBWNOZDSADJMFC-CZPYZCIJSA-N (4r,5s,6s)-3-[1-[4-[2-aminoethyl(propan-2-yl)carbamoyl]-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound NCCN(C(C)C)C(=O)C1=CSC(N2CC(C2)SC=2[C@@H]([C@H]3N(C([C@@H]3[C@@H](C)O)=O)C=2C(O)=O)C)=N1 QBWNOZDSADJMFC-CZPYZCIJSA-N 0.000 claims 1
• MLTKNTMEXMZFQB-HOJOPBEUSA-N (4r,5s,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-3-[1-[4-(piperidin-4-ylcarbamoyl)-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)SC(C1)CN1C(SC=1)=NC=1C(=O)NC1CCNCC1 MLTKNTMEXMZFQB-HOJOPBEUSA-N 0.000 claims 1
• QQVUUJNSDZWJLM-IUPFNGILSA-N (4r,5s,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-3-[1-[4-[[(3s)-pyrrolidin-3-yl]carbamoyl]-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)SC(C1)CN1C(SC=1)=NC=1C(=O)N[C@H]1CCNC1 QQVUUJNSDZWJLM-IUPFNGILSA-N 0.000 claims 1
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 114
• 125000002252 acyl group Chemical group 0.000 abstract description 9
• 239000003242 anti bacterial agent Substances 0.000 abstract description 6
• 230000000844 anti-bacterial effect Effects 0.000 abstract description 5
• 241001465754 Metazoa Species 0.000 abstract description 4
• 201000010099 disease Diseases 0.000 abstract description 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 2
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 456
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 444
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 280
• 238000006243 chemical reaction Methods 0.000 description 200
• 239000012153 distilled water Substances 0.000 description 184
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 178
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 177
• 239000000243 solution Substances 0.000 description 172
• 239000002904 solvent Substances 0.000 description 161
• 239000011541 reaction mixture Substances 0.000 description 158
• 235000019439 ethyl acetate Nutrition 0.000 description 152
• 229940093499 ethyl acetate Drugs 0.000 description 152
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 139
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 106
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• 229920006395 saturated elastomer Polymers 0.000 description 97
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 93
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 89
• 235000017557 sodium bicarbonate Nutrition 0.000 description 89
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 82
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 81
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 80
• 238000001819 mass spectrum Methods 0.000 description 68
• 230000002829 reductive effect Effects 0.000 description 68
• 238000005160 1H NMR spectroscopy Methods 0.000 description 61
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 61
• 239000010410 layer Substances 0.000 description 61
• 239000012299 nitrogen atmosphere Substances 0.000 description 58
• 239000003480 eluent Substances 0.000 description 57
• 239000007787 solid Substances 0.000 description 57
• 238000004587 chromatography analysis Methods 0.000 description 53
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 52
• 125000006239 protecting group Chemical group 0.000 description 49
• 159000000000 sodium salts Chemical class 0.000 description 48
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 39
• 239000011780 sodium chloride Substances 0.000 description 39
• 239000003795 chemical substances by application Substances 0.000 description 38
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 36
• 239000011734 sodium Substances 0.000 description 36
• 239000007858 starting material Substances 0.000 description 35
• 239000003960 organic solvent Substances 0.000 description 33
• 230000035484 reaction time Effects 0.000 description 33
• 238000001953 recrystallisation Methods 0.000 description 33
• 238000007792 addition Methods 0.000 description 32
• 239000000706 filtrate Substances 0.000 description 31
• 238000001556 precipitation Methods 0.000 description 31
• YFHNDHXQDJQEEE-UHFFFAOYSA-N acetic acid;hydrazine Chemical compound NN.CC(O)=O YFHNDHXQDJQEEE-UHFFFAOYSA-N 0.000 description 30
• 239000002585 base Substances 0.000 description 28
• 150000002170 ethers Chemical class 0.000 description 28
• 238000005406 washing Methods 0.000 description 28
• 230000002411 adverse Effects 0.000 description 27
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 27
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 26
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 25
• DMKZERWLEGTECU-UEUXDIAVSA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-diphenylphosphoryloxy-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)OC=1[C@@H]([C@@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C DMKZERWLEGTECU-UEUXDIAVSA-N 0.000 description 24
• 150000008282 halocarbons Chemical class 0.000 description 24
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 24
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 24
• 238000010898 silica gel chromatography Methods 0.000 description 23
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 22
• 150000001408 amides Chemical class 0.000 description 22
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 238000004440 column chromatography Methods 0.000 description 18
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 17
• 239000002253 acid Substances 0.000 description 17
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
• 235000011054 acetic acid Nutrition 0.000 description 15
• 230000003472 neutralizing effect Effects 0.000 description 15
• 229910052708 sodium Inorganic materials 0.000 description 15
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
• 150000001298 alcohols Chemical class 0.000 description 14
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
• 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 13
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 13
• 150000007530 organic bases Chemical class 0.000 description 13
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 13
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 150000001412 amines Chemical class 0.000 description 12
• 239000003054 catalyst Substances 0.000 description 12
• 239000000741 silica gel Substances 0.000 description 12
• 229910002027 silica gel Inorganic materials 0.000 description 12
• 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 12
• 229910052783 alkali metal Inorganic materials 0.000 description 10
• 230000003197 catalytic effect Effects 0.000 description 10
• 239000003638 chemical reducing agent Substances 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 150000002825 nitriles Chemical class 0.000 description 9
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 7
• QLSYIEGOUWSMMQ-UHFFFAOYSA-N acetonitrile;ethyl acetate Chemical compound CC#N.CC#N.CCOC(C)=O QLSYIEGOUWSMMQ-UHFFFAOYSA-N 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• 150000007529 inorganic bases Chemical class 0.000 description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 7
• 229910000027 potassium carbonate Inorganic materials 0.000 description 7
• 235000011181 potassium carbonates Nutrition 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 238000003786 synthesis reaction Methods 0.000 description 7
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 6
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
• 230000008030 elimination Effects 0.000 description 6
• 238000003379 elimination reaction Methods 0.000 description 6
• 125000005843 halogen group Chemical group 0.000 description 6
• OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
• NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
• 239000012044 organic layer Substances 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 229910000029 sodium carbonate Inorganic materials 0.000 description 6
• 235000017550 sodium carbonate Nutrition 0.000 description 6
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
• 150000007513 acids Chemical class 0.000 description 5
• 150000003863 ammonium salts Chemical class 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 150000001805 chlorine compounds Chemical class 0.000 description 5
• 125000004185 ester group Chemical group 0.000 description 5
• QVZGUPVAMOTYEB-RXMQYKEDSA-N methyl (5R)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound COC(=O)C1=CC[C@H]2N1C(C2)=O QVZGUPVAMOTYEB-RXMQYKEDSA-N 0.000 description 5
• 230000001590 oxidative effect Effects 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• 241000894006 Bacteria Species 0.000 description 4
• QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 4
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
• 125000003172 aldehyde group Chemical group 0.000 description 4
• 229910000102 alkali metal hydride Inorganic materials 0.000 description 4
• 150000008046 alkali metal hydrides Chemical class 0.000 description 4
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
• 238000010511 deprotection reaction Methods 0.000 description 4
• 239000011737 fluorine Substances 0.000 description 4
• 229910052731 fluorine Inorganic materials 0.000 description 4
• 230000007062 hydrolysis Effects 0.000 description 4
• 238000006460 hydrolysis reaction Methods 0.000 description 4
• UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 4
• 229910052751 metal Inorganic materials 0.000 description 4
• 239000002184 metal Substances 0.000 description 4
• UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 4
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
• PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 4
• 150000007524 organic acids Chemical class 0.000 description 4
• 239000007800 oxidant agent Substances 0.000 description 4
• 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 4
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
• 235000011121 sodium hydroxide Nutrition 0.000 description 4
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 4
• 235000019345 sodium thiosulphate Nutrition 0.000 description 4
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 4
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 4
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
• 125000003396 thiol group Chemical group [H]S* 0.000 description 4
• 125000005505 thiomorpholino group Chemical group 0.000 description 4
• IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 4
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• IUICOVQHLKWNIU-MWZBICOBSA-N (4R,5S)-4-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound OC(C)[C@@]1(C=C(N2[C@H]1CC2=O)C(=O)O)C IUICOVQHLKWNIU-MWZBICOBSA-N 0.000 description 3
• 125000000027 (C1-C10) alkoxy group Chemical group 0.000 description 3
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-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
• XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 3
• 238000005481 NMR spectroscopy Methods 0.000 description 3
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• 150000003973 alkyl amines Chemical class 0.000 description 3
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
• 125000003368 amide group Chemical group 0.000 description 3
• 238000005576 amination reaction Methods 0.000 description 3
• 244000052616 bacterial pathogen Species 0.000 description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 239000001768 carboxy methyl cellulose Substances 0.000 description 3
• 150000001733 carboxylic acid esters Chemical class 0.000 description 3
• 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
• 229920002678 cellulose Polymers 0.000 description 3
• 239000001913 cellulose Substances 0.000 description 3
• 125000001309 chloro group Chemical group Cl* 0.000 description 3
• 238000007796 conventional method Methods 0.000 description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
• LUSOXMRLFYFZJY-UYVJDWJCSA-N ethyl 2-[3-[[(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-2-[(4-nitrophenyl)methoxycarbonyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-en-3-yl]sulfanyl]azetidin-1-yl]-1,3-thiazole-4-carboxylate Chemical compound C(C)OC(=O)C=1N=C(SC=1)N1CC(C1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C LUSOXMRLFYFZJY-UYVJDWJCSA-N 0.000 description 3
• WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 3
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 3
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 3
• 150000003003 phosphines Chemical class 0.000 description 3
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
• 235000011118 potassium hydroxide Nutrition 0.000 description 3
• 230000003389 potentiating effect Effects 0.000 description 3
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 3
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
• 229910052938 sodium sulfate Inorganic materials 0.000 description 3
• 235000011152 sodium sulphate Nutrition 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 150000003512 tertiary amines Chemical class 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 3
• FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 2
• QXCZGCMHZLMLIV-YMHOJLSTSA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-[(3S)-1-(4-cyano-1,3-thiazol-2-yl)pyrrolidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(#N)C=1N=C(SC=1)N1C[C@H](CC1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C QXCZGCMHZLMLIV-YMHOJLSTSA-N 0.000 description 2
• AWJXQANAOWPSSG-GWIYSAMLSA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(N)(=O)C=1N=C(SC=1)N1CC(C1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C AWJXQANAOWPSSG-GWIYSAMLSA-N 0.000 description 2
• KYKVSSWLARKODB-YTFOQLDISA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-[1-(4-cyano-1,3-thiazol-2-yl)azetidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(#N)C=1N=C(SC=1)N1CC(C1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C KYKVSSWLARKODB-YTFOQLDISA-N 0.000 description 2
• DUTGOUDJTQFBPC-AHWCRGGASA-N (4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-3-[1-[4-(morpholine-4-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound O1CCN(CC1)C(=O)C=1N=C(SC=1)N1CC(C1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C DUTGOUDJTQFBPC-AHWCRGGASA-N 0.000 description 2
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 2
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 description 2
• RHUYHJGZWVXEHW-UHFFFAOYSA-N 1,1-Dimethyhydrazine Chemical compound CN(C)N RHUYHJGZWVXEHW-UHFFFAOYSA-N 0.000 description 2
• KGENPKAWPRUNIG-UHFFFAOYSA-N 1-[chloro(ethyl)phosphoryl]ethane Chemical compound CCP(Cl)(=O)CC KGENPKAWPRUNIG-UHFFFAOYSA-N 0.000 description 2
• BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical class OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 2
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 2
• JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 2
• OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
• UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 description 2
• ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 2
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
• 229920000881 Modified starch Polymers 0.000 description 2
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• 206010057190 Respiratory tract infections Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• 229940022663 acetate Drugs 0.000 description 2
• 150000001243 acetic acids Chemical class 0.000 description 2
• 150000008065 acid anhydrides Chemical class 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
• 239000002168 alkylating agent Substances 0.000 description 2
• 229940100198 alkylating agent Drugs 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 125000000266 alpha-aminoacyl group Chemical group 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 239000003849 aromatic solvent Substances 0.000 description 2
• 239000007853 buffer solution Substances 0.000 description 2
• OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
• 239000007810 chemical reaction solvent Substances 0.000 description 2
• DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• 230000000052 comparative effect Effects 0.000 description 2
• 238000009833 condensation Methods 0.000 description 2
• 230000005494 condensation Effects 0.000 description 2
• 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
• XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 description 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 2
• YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 2
• VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 2
• 229940043279 diisopropylamine Drugs 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 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 2
• 238000004821 distillation Methods 0.000 description 2
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
• LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 2
• 229910052736 halogen Inorganic materials 0.000 description 2
• 125000001072 heteroaryl group Chemical group 0.000 description 2
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 150000004678 hydrides Chemical class 0.000 description 2
• 150000002430 hydrocarbons Chemical group 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 2
• 150000002576 ketones Chemical class 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
• 238000005259 measurement Methods 0.000 description 2
• 229940101209 mercuric oxide Drugs 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
• LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
• 235000019426 modified starch Nutrition 0.000 description 2
• 125000001624 naphthyl group Chemical group 0.000 description 2
• 238000006386 neutralization reaction Methods 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
• 150000002941 palladium compounds Chemical class 0.000 description 2
• 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
• 239000000825 pharmaceutical preparation Substances 0.000 description 2
• HTKKQUNNOCVIHK-YLGOIMDESA-N phenyl (4r,5s,6s)-3-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]sulfanyl-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(=O)OC=1C=CC=CC=1)=O)[C@H](O)C)SC(C1)CN1C1=NC(C(N)=O)=CS1 HTKKQUNNOCVIHK-YLGOIMDESA-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
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 230000000865 phosphorylative effect Effects 0.000 description 2
• 229910052697 platinum Inorganic materials 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 2
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
• 238000000039 preparative column chromatography Methods 0.000 description 2
• 238000012746 preparative thin layer chromatography Methods 0.000 description 2
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
• 239000012264 purified product Substances 0.000 description 2
• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 210000002966 serum Anatomy 0.000 description 2
• 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 2
• BABPEPRNSRIYFA-UHFFFAOYSA-N silyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)O[SiH3] BABPEPRNSRIYFA-UHFFFAOYSA-N 0.000 description 2
• QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• YZYDOFGGDSDUPX-UHFFFAOYSA-M sodium;carbonic acid;chloride Chemical compound [Na+].[Cl-].OC(O)=O YZYDOFGGDSDUPX-UHFFFAOYSA-M 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 238000003756 stirring Methods 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 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 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
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 2
• DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 2
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 2
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
• PTDVPWWJRCOIIO-UHFFFAOYSA-N (4-methoxyphenyl)methanethiol Chemical class COC1=CC=C(CS)C=C1 PTDVPWWJRCOIIO-UHFFFAOYSA-N 0.000 description 1
• PDVFSPNIEOYOQL-UHFFFAOYSA-N (4-methylphenyl)sulfonyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OS(=O)(=O)C1=CC=C(C)C=C1 PDVFSPNIEOYOQL-UHFFFAOYSA-N 0.000 description 1
• BIPHRHRBODLUGV-QKMWEODOSA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-[(3S)-1-(4-carbamoyl-1,3-thiazol-2-yl)pyrrolidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(N)(=O)C=1N=C(SC=1)N1C[C@H](CC1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C BIPHRHRBODLUGV-QKMWEODOSA-N 0.000 description 1
• SPAGFGQIFPRTLJ-GWIYSAMLSA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-[1-(4-carbamoyl-1,3-oxazol-2-yl)azetidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(N)(=O)C=1N=C(OC=1)N1CC(C1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C SPAGFGQIFPRTLJ-GWIYSAMLSA-N 0.000 description 1
• PTTLZFFCIZHQFF-UYVJDWJCSA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-[1-(4-carbamoyl-1,3-thiazol-2-yl)piperidin-4-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(N)(=O)C=1N=C(SC=1)N1CCC(CC1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C PTTLZFFCIZHQFF-UYVJDWJCSA-N 0.000 description 1
• KPLJIHFJVOXNMQ-YTFOQLDISA-N (4-nitrophenyl)methyl (4R,5S,6S)-3-[1-(4-cyano-1,3-oxazol-2-yl)azetidin-3-yl]sulfanyl-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(#N)C=1N=C(OC=1)N1CC(C1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C KPLJIHFJVOXNMQ-YTFOQLDISA-N 0.000 description 1
• IULOMHDXEKXQJF-YTFOQLDISA-N (4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-[1-[4-(hydroxymethyl)-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound OCC=1N=C(SC=1)N1CC(C1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C IULOMHDXEKXQJF-YTFOQLDISA-N 0.000 description 1
• OPHUCTGZCKZNFM-AHWCRGGASA-N (4-nitrophenyl)methyl (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[1-[4-(pyrrolidine-1-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound N1(CCCC1)C(=O)C=1N=C(SC=1)N1CC(C1)SC=1[C@@H]([C@H]2N(C=1C(=O)OCC1=CC=C(C=C1)[N+](=O)[O-])C([C@@H]2[C@@H](C)O)=O)C OPHUCTGZCKZNFM-AHWCRGGASA-N 0.000 description 1
• DHGLTNRRMBQJAF-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-(3-acetylsulfanylazetidin-1-yl)-1,3-thiazole-4-carboxylate Chemical compound C1C(SC(=O)C)CN1C1=NC(C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)=CS1 DHGLTNRRMBQJAF-UHFFFAOYSA-N 0.000 description 1
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
• WQVOUANKVCYEIQ-UHFFFAOYSA-N 1,3-thiazol-4-ylmethanol Chemical compound OCC1=CSC=N1 WQVOUANKVCYEIQ-UHFFFAOYSA-N 0.000 description 1
• PNAFRZGWUVQUKH-UHFFFAOYSA-N 1,3-thiazole-4-carbonitrile Chemical compound N#CC1=CSC=N1 PNAFRZGWUVQUKH-UHFFFAOYSA-N 0.000 description 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 1
• XZVBIIRIWFZJOE-UHFFFAOYSA-N 1-iodoethyl propan-2-yl carbonate Chemical compound CC(C)OC(=O)OC(C)I XZVBIIRIWFZJOE-UHFFFAOYSA-N 0.000 description 1
• 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
• RNTZHHSDUJMSMB-OJQFGAJUSA-N 1-pentan-3-yloxycarbonyloxyethyl (4r,5s,6s)-3-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]sulfanyl-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound O=C([C@H]([C@@H](C)O)[C@H]1[C@H]2C)N1C(C(=O)OC(C)OC(=O)OC(CC)CC)=C2SC(C1)CN1C1=NC(C(N)=O)=CS1 RNTZHHSDUJMSMB-OJQFGAJUSA-N 0.000 description 1
• 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 1
• CJFIXLWEIYAZRB-YIKOMLBNSA-N 2,2-dimethylpropanoyloxymethyl (4r,5s,6s)-3-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]sulfanyl-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(=O)OCOC(=O)C(C)(C)C)=O)[C@H](O)C)SC(C1)CN1C1=NC(C(N)=O)=CS1 CJFIXLWEIYAZRB-YIKOMLBNSA-N 0.000 description 1
• QIJIUJYANDSEKG-UHFFFAOYSA-N 2,4,4-trimethylpentan-2-amine Chemical class CC(C)(C)CC(C)(C)N QIJIUJYANDSEKG-UHFFFAOYSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• KLTIMEXKPRJOIS-UHFFFAOYSA-N 2-chloro-1-methyl-2H-pyridine hydroiodide Chemical compound I.CN1C=CC=CC1Cl KLTIMEXKPRJOIS-UHFFFAOYSA-N 0.000 description 1
• FZZMTSNZRBFGGU-UHFFFAOYSA-N 2-chloro-7-fluoroquinazolin-4-amine Chemical compound FC1=CC=C2C(N)=NC(Cl)=NC2=C1 FZZMTSNZRBFGGU-UHFFFAOYSA-N 0.000 description 1
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
• 125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 1
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 description 1
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
• 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 244000291564 Allium cepa Species 0.000 description 1
• 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
• 241000790232 Anisia Species 0.000 description 1
• 244000063299 Bacillus subtilis Species 0.000 description 1
• 235000014469 Bacillus subtilis Nutrition 0.000 description 1
• 241000606125 Bacteroides Species 0.000 description 1
• 108020004256 Beta-lactamase Proteins 0.000 description 1
• ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
• 125000000041 C6-C10 aryl group Chemical group 0.000 description 1
• DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• 102100036883 Cyclin-H Human genes 0.000 description 1
• 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 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 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 1
• 229920002307 Dextran Polymers 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• 239000004375 Dextrin Substances 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
• BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical class C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• 102100020743 Dipeptidase 1 Human genes 0.000 description 1
• 108090000204 Dipeptidase 1 Proteins 0.000 description 1
• 241000588914 Enterobacter Species 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 108090000371 Esterases Proteins 0.000 description 1
• 241000192125 Firmicutes Species 0.000 description 1
• KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
• 108010010803 Gelatin 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
• 229920000084 Gum arabic Polymers 0.000 description 1
• 241000606768 Haemophilus influenzae Species 0.000 description 1
• 101000713120 Homo sapiens Cyclin-H Proteins 0.000 description 1
• 241000588747 Klebsiella pneumoniae Species 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical class NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 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
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 239000012448 Lithium borohydride Substances 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical class SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
• 239000004368 Modified starch Substances 0.000 description 1
• 241000699666 Mus <mouse, genus> Species 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 241000588769 Proteus <enterobacteria> Species 0.000 description 1
• 241000589516 Pseudomonas Species 0.000 description 1
• 239000004373 Pullulan Substances 0.000 description 1
• 229920001218 Pullulan Polymers 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• 241000607720 Serratia Species 0.000 description 1
• 241000607768 Shigella Species 0.000 description 1
• XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 241000191940 Staphylococcus Species 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 241000193998 Streptococcus pneumoniae Species 0.000 description 1
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• NFUHGQVNWQOHQB-FIKXEGEWSA-N [2H]C(C(C(=O)O[Si](C)(C)C)([2H])[2H])[2H].[Na] Chemical compound [2H]C(C(C(=O)O[Si](C)(C)C)([2H])[2H])[2H].[Na] NFUHGQVNWQOHQB-FIKXEGEWSA-N 0.000 description 1
• YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
• CVNMBKFJYRAHPO-UHFFFAOYSA-N [chloro(methyl)phosphoryl]methane Chemical compound CP(C)(Cl)=O CVNMBKFJYRAHPO-UHFFFAOYSA-N 0.000 description 1
• WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 239000002535 acidifier Substances 0.000 description 1
• 125000005042 acyloxymethyl group Chemical group 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000001361 adipic acid Substances 0.000 description 1
• 235000011037 adipic acid Nutrition 0.000 description 1
• 125000001980 alanyl group Chemical group 0.000 description 1
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
• 150000008041 alkali metal carbonates Chemical class 0.000 description 1
• 150000001351 alkyl iodides Chemical class 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 229950003476 aminothiazole Drugs 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 125000000637 arginyl group Chemical class N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 1
• 150000004982 aromatic amines Chemical class 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
• 125000005129 aryl carbonyl group Chemical group 0.000 description 1
• 125000005228 aryl sulfonate group Chemical group 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• FDPKMJDUXJFKOI-UHFFFAOYSA-N azetidin-3-amine Chemical compound NC1CNC1 FDPKMJDUXJFKOI-UHFFFAOYSA-N 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 125000004069 aziridinyl group Chemical group 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical class C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
• 229960000686 benzalkonium chloride Drugs 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
• PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• 229960004217 benzyl alcohol Drugs 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 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
• 102000006635 beta-lactamase Human genes 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000010170 biological method Methods 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
• 239000004327 boric acid Substances 0.000 description 1
• 229910052796 boron Inorganic materials 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
• ZMCUDHNSHCRDBT-UHFFFAOYSA-M caesium bicarbonate Chemical compound [Cs+].OC([O-])=O ZMCUDHNSHCRDBT-UHFFFAOYSA-M 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
• 229910052791 calcium Inorganic materials 0.000 description 1
• 235000001465 calcium Nutrition 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 125000001589 carboacyl group Chemical group 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
• 150000001728 carbonyl compounds Chemical class 0.000 description 1
• 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 150000001734 carboxylic acid salts Chemical class 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
• 229910001919 chlorite Inorganic materials 0.000 description 1
• 229910052619 chlorite group Inorganic materials 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
• 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
• 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
• VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• QBWCMBCROVPCKQ-UHFFFAOYSA-N chlorous acid Chemical compound OCl=O QBWCMBCROVPCKQ-UHFFFAOYSA-N 0.000 description 1
• 229940001468 citrate Drugs 0.000 description 1
• 150000001868 cobalt Chemical class 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 150000001879 copper Chemical class 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 229930003836 cresol Natural products 0.000 description 1
• 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 1
• JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• 125000003074 decanoyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 125000006003 dichloroethyl group Chemical group 0.000 description 1
• QRXRNRCEZBBKEU-UHFFFAOYSA-N dichloromethane;2-methylpropan-2-ol;oxolane;hydrate Chemical compound O.ClCCl.CC(C)(C)O.C1CCOC1 QRXRNRCEZBBKEU-UHFFFAOYSA-N 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
• 125000006001 difluoroethyl group Chemical group 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
• BADXJIPKFRBFOT-UHFFFAOYSA-N dimedone Chemical compound CC1(C)CC(=O)CC(=O)C1 BADXJIPKFRBFOT-UHFFFAOYSA-N 0.000 description 1
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
• XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
• HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940079593 drug Drugs 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 1
• NLVXSWCKKBEXTG-UHFFFAOYSA-M ethenesulfonate Chemical compound [O-]S(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-M 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• OVCARGJAVNIOGP-NRMKKVEVSA-N ethyl (4r,5s,6s)-3-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl]sulfanyl-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound O=C([C@H]([C@@H](C)O)[C@H]1[C@H]2C)N1C(C(=O)OCC)=C2SC(C1)CN1C1=NC(C(N)=O)=CS1 OVCARGJAVNIOGP-NRMKKVEVSA-N 0.000 description 1
• AWJREIUOAQMFSN-UHFFFAOYSA-N ethyl 2-(3-acetylsulfanylazetidin-1-yl)-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(N2CC(C2)SC(C)=O)=N1 AWJREIUOAQMFSN-UHFFFAOYSA-N 0.000 description 1
• ITKXJNFHVWGYPD-UHFFFAOYSA-N ethyl 2-(4-acetylsulfanylpiperidin-1-yl)-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(N2CCC(CC2)SC(C)=O)=N1 ITKXJNFHVWGYPD-UHFFFAOYSA-N 0.000 description 1
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 125000005816 fluoropropyl group Chemical group [H]C([H])(F)C([H])([H])C([H])([H])* 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 239000008273 gelatin Substances 0.000 description 1
• 229920000159 gelatin Polymers 0.000 description 1
• 235000019322 gelatine Nutrition 0.000 description 1
• 235000011852 gelatine desserts Nutrition 0.000 description 1
• 150000002301 glucosamine derivatives Chemical class 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 150000002332 glycine derivatives Chemical class 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 229940047650 haemophilus influenzae Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000002140 halogenating effect Effects 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 125000005935 hexyloxycarbonyl group Chemical group 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
• 229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
• 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 239000002198 insoluble material Substances 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• PELJISAVHGXLAL-UHFFFAOYSA-N iodomethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCI PELJISAVHGXLAL-UHFFFAOYSA-N 0.000 description 1
• 238000004255 ion exchange chromatography Methods 0.000 description 1
• 150000002505 iron Chemical class 0.000 description 1
• LRDFRRGEGBBSRN-UHFFFAOYSA-N isobutyronitrile Chemical compound CC(C)C#N LRDFRRGEGBBSRN-UHFFFAOYSA-N 0.000 description 1
• 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 description 1
• ZBKFYXZXZJPWNQ-UHFFFAOYSA-N isothiocyanate group Chemical group [N-]=C=S ZBKFYXZXZJPWNQ-UHFFFAOYSA-N 0.000 description 1
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 125000001998 leucyl group Chemical group 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 1
• 229910000103 lithium hydride Inorganic materials 0.000 description 1
• 229910003002 lithium salt Inorganic materials 0.000 description 1
• 159000000002 lithium salts Chemical class 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
• 229960003511 macrogol Drugs 0.000 description 1
• 229940037627 magnesium lauryl sulfate Drugs 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 description 1
• 229940049920 malate Drugs 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
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 229960002523 mercuric chloride Drugs 0.000 description 1
• LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 1
• AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
• 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• RPNNPZHFJPXFQS-UHFFFAOYSA-N methane;rhodium Chemical compound C.[Rh] RPNNPZHFJPXFQS-UHFFFAOYSA-N 0.000 description 1
• AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
• UCFFGYASXIPWPD-UHFFFAOYSA-N methyl hypochlorite Chemical compound COCl UCFFGYASXIPWPD-UHFFFAOYSA-N 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
• 229960002216 methylparaben Drugs 0.000 description 1
• BDGDWWGTAFXEEW-UHFFFAOYSA-N methylsulfinylmethane;oxalyl dichloride Chemical compound CS(C)=O.ClC(=O)C(Cl)=O BDGDWWGTAFXEEW-UHFFFAOYSA-N 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 150000002780 morpholines Chemical class 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• XXZNFWHGOMHWCO-UHFFFAOYSA-N n,n-diethylthiohydroxylamine Chemical compound CCN(S)CC XXZNFWHGOMHWCO-UHFFFAOYSA-N 0.000 description 1
• DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-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
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([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
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 231100000417 nephrotoxicity Toxicity 0.000 description 1
• 150000002815 nickel Chemical class 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 229940039748 oxalate Drugs 0.000 description 1
• 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
• 125000003566 oxetanyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 125000000466 oxiranyl group Chemical group 0.000 description 1
• 229940045657 oxycide Drugs 0.000 description 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• 229940049954 penicillin Drugs 0.000 description 1
• 125000001148 pentyloxycarbonyl group Chemical group 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• 125000000405 phenylalanyl group Chemical group 0.000 description 1
• 229940067107 phenylethyl alcohol Drugs 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 150000003014 phosphoric acid esters Chemical class 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
• 125000005633 phthalidyl group Chemical group 0.000 description 1
• 150000004885 piperazines Chemical class 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• YOQJEVPCVRJMPN-UHFFFAOYSA-N piperidin-1-yl(1,3-thiazol-4-yl)methanone Chemical compound C=1SC=NC=1C(=O)N1CCCCC1 YOQJEVPCVRJMPN-UHFFFAOYSA-N 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 229940068968 polysorbate 80 Drugs 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 235000015497 potassium bicarbonate Nutrition 0.000 description 1
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
• 239000011736 potassium bicarbonate Substances 0.000 description 1
• 239000011698 potassium fluoride Substances 0.000 description 1
• 235000003270 potassium fluoride Nutrition 0.000 description 1
• 229910000105 potassium hydride Inorganic materials 0.000 description 1
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 239000012286 potassium permanganate Substances 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical class CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 239000000047 product Substances 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
• 229960003415 propylparaben Drugs 0.000 description 1
• UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 235000019423 pullulan Nutrition 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• HJCYVFCAWVFFGS-UHFFFAOYSA-N pyrrolidin-1-yl(1,3-thiazol-4-yl)methanone Chemical compound C=1SC=NC=1C(=O)N1CCCC1 HJCYVFCAWVFFGS-UHFFFAOYSA-N 0.000 description 1
• 210000002345 respiratory system Anatomy 0.000 description 1
• 208000020029 respiratory tract infectious disease Diseases 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• 238000007363 ring formation reaction Methods 0.000 description 1
• QRYNEEDPQORHFJ-SSDOTTSWSA-N s-[(3r)-1-(4-carbamoyl-1,3-thiazol-2-yl)pyrrolidin-3-yl] ethanethioate Chemical compound C1[C@H](SC(=O)C)CCN1C1=NC(C(N)=O)=CS1 QRYNEEDPQORHFJ-SSDOTTSWSA-N 0.000 description 1
• QRYNEEDPQORHFJ-ZETCQYMHSA-N s-[(3s)-1-(4-carbamoyl-1,3-thiazol-2-yl)pyrrolidin-3-yl] ethanethioate Chemical compound C1[C@@H](SC(=O)C)CCN1C1=NC(C(N)=O)=CS1 QRYNEEDPQORHFJ-ZETCQYMHSA-N 0.000 description 1
• QQQYKQZVTHJBEK-VIFPVBQESA-N s-[(3s)-1-(4-cyano-1,3-thiazol-2-yl)pyrrolidin-3-yl] ethanethioate Chemical compound C1[C@@H](SC(=O)C)CCN1C1=NC(C#N)=CS1 QQQYKQZVTHJBEK-VIFPVBQESA-N 0.000 description 1
• WAZWVHRDUISFCU-UHFFFAOYSA-N s-[1-(4-carbamoyl-1,3-oxazol-2-yl)azetidin-3-yl] ethanethioate Chemical compound C1C(SC(=O)C)CN1C1=NC(C(N)=O)=CO1 WAZWVHRDUISFCU-UHFFFAOYSA-N 0.000 description 1
• WPIPSMMTXGIQNH-UHFFFAOYSA-N s-[1-(4-carbamoyl-1,3-thiazol-2-yl)azetidin-3-yl] ethanethioate Chemical compound C1C(SC(=O)C)CN1C1=NC(C(N)=O)=CS1 WPIPSMMTXGIQNH-UHFFFAOYSA-N 0.000 description 1
• NYKZCXGLMZXQCN-UHFFFAOYSA-N s-[1-(4-cyano-1,3-oxazol-2-yl)azetidin-3-yl] ethanethioate Chemical compound C1C(SC(=O)C)CN1C1=NC(C#N)=CO1 NYKZCXGLMZXQCN-UHFFFAOYSA-N 0.000 description 1
• AFPNCHHOJYHEPW-UHFFFAOYSA-N s-[1-(4-cyano-1,3-thiazol-2-yl)azetidin-3-yl] ethanethioate Chemical compound C1C(SC(=O)C)CN1C1=NC(C#N)=CS1 AFPNCHHOJYHEPW-UHFFFAOYSA-N 0.000 description 1
• WPZQETWMRLWTBY-UHFFFAOYSA-N s-[1-[4-(4-methylpiperazine-1-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl] ethanethioate Chemical compound C1CN(C)CCN1C(=O)C1=CSC(N2CC(C2)SC(C)=O)=N1 WPZQETWMRLWTBY-UHFFFAOYSA-N 0.000 description 1
• CQLXEZKARWQZAA-UHFFFAOYSA-N s-[1-[4-(morpholine-4-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl] ethanethioate Chemical compound C1C(SC(=O)C)CN1C1=NC(C(=O)N2CCOCC2)=CS1 CQLXEZKARWQZAA-UHFFFAOYSA-N 0.000 description 1
• QPVXDBXBPJQEJT-UHFFFAOYSA-N s-[1-[4-(piperidine-1-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl] ethanethioate Chemical compound C1C(SC(=O)C)CN1C1=NC(C(=O)N2CCCCC2)=CS1 QPVXDBXBPJQEJT-UHFFFAOYSA-N 0.000 description 1
• BSGDYKDDIPDARP-UHFFFAOYSA-N s-[1-[4-(pyrrolidine-1-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl] ethanethioate Chemical compound C1C(SC(=O)C)CN1C1=NC(C(=O)N2CCCC2)=CS1 BSGDYKDDIPDARP-UHFFFAOYSA-N 0.000 description 1
• OXAWMESCTMQVIE-UHFFFAOYSA-N s-[1-[4-(thiomorpholine-4-carbonyl)-1,3-thiazol-2-yl]azetidin-3-yl] ethanethioate Chemical compound C1C(SC(=O)C)CN1C1=NC(C(=O)N2CCSCC2)=CS1 OXAWMESCTMQVIE-UHFFFAOYSA-N 0.000 description 1
• AKDPYTPSRUPJCF-UHFFFAOYSA-N s-[1-[4-[2-(4-nitrophenyl)acetyl]-1,3-thiazol-2-yl]piperidin-4-yl] ethanethioate Chemical compound C1CC(SC(=O)C)CCN1C1=NC(C(=O)CC=2C=CC(=CC=2)[N+]([O-])=O)=CS1 AKDPYTPSRUPJCF-UHFFFAOYSA-N 0.000 description 1
• 229930195734 saturated hydrocarbon Natural products 0.000 description 1
• 229960001153 serine Drugs 0.000 description 1
• 150000004760 silicates Chemical class 0.000 description 1
• 229910052710 silicon Inorganic materials 0.000 description 1
• 239000010703 silicon Substances 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 239000001632 sodium acetate Substances 0.000 description 1
• 235000017281 sodium acetate Nutrition 0.000 description 1
• WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
• 239000004299 sodium benzoate Substances 0.000 description 1
• 235000010234 sodium benzoate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
• 229960002218 sodium chlorite Drugs 0.000 description 1
• 235000009518 sodium iodide Nutrition 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• 229910000162 sodium phosphate Inorganic materials 0.000 description 1
• 235000011008 sodium phosphates Nutrition 0.000 description 1
• VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
• RBBWNXJFTBCLKT-UHFFFAOYSA-M sodium;ethanethioate Chemical compound [Na+].CC([S-])=O RBBWNXJFTBCLKT-UHFFFAOYSA-M 0.000 description 1
• HMTFGKVHBABVOV-UHFFFAOYSA-M sodium;propanethioate Chemical compound [Na+].CCC([O-])=S HMTFGKVHBABVOV-UHFFFAOYSA-M 0.000 description 1
• JTHUJOZLDHAGIH-UHFFFAOYSA-M sodium;thiobenzate Chemical compound [Na+].[O-]C(=S)C1=CC=CC=C1 JTHUJOZLDHAGIH-UHFFFAOYSA-M 0.000 description 1
• 239000012453 solvate Substances 0.000 description 1
• 239000011877 solvent mixture 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
• 239000000600 sorbitol Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 239000012177 spermaceti Substances 0.000 description 1
• 229940084106 spermaceti Drugs 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
• 229940086735 succinate Drugs 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 229940095064 tartrate Drugs 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
• 238000012360 testing method Methods 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• 150000003566 thiocarboxylic acids Chemical class 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 125000005425 toluyl group Chemical group 0.000 description 1
• 150000003852 triazoles Chemical class 0.000 description 1
• 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• 150000004684 trihydrates Chemical class 0.000 description 1
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 150000003952 β-lactams Chemical class 0.000 description 1