JP5869701B2 - アミジン置換β−ラクタム化合物類、それらの調製及び抗菌剤 - Google Patents

Info

Publication number

JP5869701B2

JP5869701B2 JP2014553696A JP2014553696A JP5869701B2 JP 5869701 B2 JP5869701 B2 JP 5869701B2 JP 2014553696 A JP2014553696 A JP 2014553696A JP 2014553696 A JP2014553696 A JP 2014553696A JP 5869701 B2 JP5869701 B2 JP 5869701B2

Authority

JP

Japan

Prior art keywords

amino

thiazol

imino

ethoxy

methyl

Prior art date

2012-01-24

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• Discuss

• -1 β-lactam compounds Chemical class 0.000 title claims description 336
• 238000002360 preparation method Methods 0.000 title claims description 6
• 239000003242 anti bacterial agent Substances 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims description 435
• 125000001424 substituent group Chemical group 0.000 claims description 63
• 125000000217 alkyl group Chemical group 0.000 claims description 61
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 59
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 58
• 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims description 47
• 150000003839 salts Chemical class 0.000 claims description 47
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 45
• 229910052739 hydrogen Inorganic materials 0.000 claims description 43
• 238000000034 method Methods 0.000 claims description 43
• 239000001257 hydrogen Substances 0.000 claims description 42
• 239000012453 solvate Substances 0.000 claims description 39
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
• 125000001072 heteroaryl group Chemical group 0.000 claims description 35
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 34
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 33
• 125000000623 heterocyclic group Chemical group 0.000 claims description 32
• 229910052736 halogen Inorganic materials 0.000 claims description 31
• 150000002367 halogens Chemical class 0.000 claims description 31
• 235000019260 propionic acid Nutrition 0.000 claims description 30
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 25
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
• 229910052757 nitrogen Inorganic materials 0.000 claims description 20
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 20
• 125000003118 aryl group Chemical group 0.000 claims description 19
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 17
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 16
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 15
• 125000005842 heteroatom Chemical group 0.000 claims description 15
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14
• 229910052717 sulfur Inorganic materials 0.000 claims description 14
• 241000894006 Bacteria Species 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 13
• 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 claims description 13
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 12
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
• 229910052760 oxygen Inorganic materials 0.000 claims description 11
• 208000035143 Bacterial infection Diseases 0.000 claims description 10
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 10
• 125000004432 carbon atom Chemical group C* 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 239000002253 acid Substances 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 9
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 8
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 8
• 229910052799 carbon Inorganic materials 0.000 claims description 8
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
• 125000006239 protecting group Chemical group 0.000 claims description 7
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 150000001721 carbon Chemical group 0.000 claims description 6
• 201000010099 disease Diseases 0.000 claims description 6
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
• 241001465754 Metazoa Species 0.000 claims description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims description 5
• 239000003781 beta lactamase inhibitor Substances 0.000 claims description 5
• 229940126813 beta-lactamase inhibitor Drugs 0.000 claims description 5
• 239000003795 chemical substances by application Substances 0.000 claims description 5
• 230000006806 disease prevention Effects 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical group C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
• 231100000252 nontoxic Toxicity 0.000 claims description 3
• 230000003000 nontoxic effect Effects 0.000 claims description 3
• 229940126085 β‑Lactamase Inhibitor Drugs 0.000 claims description 3
• LJCJRRKKAKAKRV-UHFFFAOYSA-N (2-amino-2-methylpropyl) 3-(3,5-ditert-butyl-4-hydroxyphenyl)propanoate Chemical group CC(C)(N)COC(=O)CCC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 LJCJRRKKAKAKRV-UHFFFAOYSA-N 0.000 claims description 2
• UBHAMQJKGHLMIT-WVBONNFESA-N (2S,3S)-3-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoyl-3-hydroxyphenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCCOc1ccc(C(N)=N)c(O)c1 UBHAMQJKGHLMIT-WVBONNFESA-N 0.000 claims description 2
• GFTKQOZYMBRHLW-QMRYPOTESA-N (2r,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoylphenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1 GFTKQOZYMBRHLW-QMRYPOTESA-N 0.000 claims description 2
• SKVPTGPGVYUKJR-ALBNSVILSA-N (2r,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[3-(4-carbamimidoylphenoxy)propoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCCOC1=CC=C(C(N)=N)C=C1 SKVPTGPGVYUKJR-ALBNSVILSA-N 0.000 claims description 2
• JLGWQOHUGYAIPH-FIWXLPQASA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[1-(4-carbamimidoylphenoxy)-2-methylpropan-2-yl]oxyiminoacetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OC(C)(C)COC1=CC=C(C(N)=N)C=C1 JLGWQOHUGYAIPH-FIWXLPQASA-N 0.000 claims description 2
• NZKYITYKDCIWHL-OQMYIJJMSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(2-bromo-4-carbamimidoylphenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1Br NZKYITYKDCIWHL-OQMYIJJMSA-N 0.000 claims description 2
• DTMMNMMGXGFBAO-AAGJFWKWSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(3-carbamimidoylphenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=CC(C(N)=N)=C1 DTMMNMMGXGFBAO-AAGJFWKWSA-N 0.000 claims description 2
• SKQTUKQCAGKOCN-MKAGAKJLSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoyl-3-methylphenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C(C)=C1 SKQTUKQCAGKOCN-MKAGAKJLSA-N 0.000 claims description 2
• HVSMMSWRHJEZMN-OSPXMHHYSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoylphenoxy)ethoxyimino]acetyl]amino]-2-carbamoyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@H](C(=O)N)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1 HVSMMSWRHJEZMN-OSPXMHHYSA-N 0.000 claims description 2
• GFTKQOZYMBRHLW-AAGJFWKWSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoylphenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1 GFTKQOZYMBRHLW-AAGJFWKWSA-N 0.000 claims description 2
• VRRBINQEFCBPQZ-XWPUJFQCSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(5-carbamimidoyl-1-methylpyrazol-3-yl)oxyethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=NN(C)C(C(N)=N)=C1 VRRBINQEFCBPQZ-XWPUJFQCSA-N 0.000 claims description 2
• ZTQPFIAOJPJHSN-XWPUJFQCSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(5-carbamimidoyl-2-methylpyrazol-3-yl)oxyethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC(C(N)=N)=NN1C ZTQPFIAOJPJHSN-XWPUJFQCSA-N 0.000 claims description 2
• FYKRFWSZFUVLHR-MNEFGQSUSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(5-carbamimidoylpyrazin-2-yl)oxyethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CN=C(C(N)=N)C=N1 FYKRFWSZFUVLHR-MNEFGQSUSA-N 0.000 claims description 2
• MTJGXFWPXMNJML-MNEFGQSUSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(6-carbamimidoylpyridazin-3-yl)oxyethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)N=N1 MTJGXFWPXMNJML-MNEFGQSUSA-N 0.000 claims description 2
• UHTJHBHEACMBDR-GNAXJGCWSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[(4-carbamimidoyl-1,3-thiazol-2-yl)oxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=NC(C(N)=N)=CS1 UHTJHBHEACMBDR-GNAXJGCWSA-N 0.000 claims description 2
• QOVJNCBNZXHFDB-AAGJFWKWSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-[(z)-n'-hydroxycarbamimidoyl]phenoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(\N)=N\O)C=C1 QOVJNCBNZXHFDB-AAGJFWKWSA-N 0.000 claims description 2
• HRSSWXGPJZJSAQ-JUBZOZOPSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-[n'-(2-hydroxyethyl)carbamimidoyl]phenoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=NCCO)C=C1 HRSSWXGPJZJSAQ-JUBZOZOPSA-N 0.000 claims description 2
• PNLORJIXBJEDMO-WRPWDPOMSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-carbamimidoyl-2-(formyloxymethyl)phenoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1COC=O PNLORJIXBJEDMO-WRPWDPOMSA-N 0.000 claims description 2
• YJACTACBEKOFKK-RUHVQPKUSA-N (2s,3s)-3-[[(2z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoylphenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C1=C(SC(N)=N1)Cl)=N/OCCOC1=CC=C(C(N)=N)C=C1 YJACTACBEKOFKK-RUHVQPKUSA-N 0.000 claims description 2
• FMFTXNRDPROUFR-OQMYIJJMSA-N (2s,3s)-3-[[(2z)-2-[2-(2-amino-4-carbamimidoylphenoxy)ethoxyimino]-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1N FMFTXNRDPROUFR-OQMYIJJMSA-N 0.000 claims description 2
• LVMHGUJLUPQJSK-QEYCWDPCSA-N (2s,3s)-3-[[(2z)-2-[2-[4-(2-amino-2-iminoethyl)phenoxy]ethoxyimino]-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(CC(N)=N)C=C1 LVMHGUJLUPQJSK-QEYCWDPCSA-N 0.000 claims description 2
• YOTRRQGYOHCXKO-YKVGDQEKSA-N 2-[[amino-[4-[2-[(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(3s)-2,2-dimethyl-4-oxo-1-sulfooxyazetidin-3-yl]amino]-2-oxoethylidene]amino]oxyethoxy]phenyl]methylidene]amino]acetic acid Chemical compound O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=NCC(O)=O)C=C1 YOTRRQGYOHCXKO-YKVGDQEKSA-N 0.000 claims description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
• NYNWPBAFYJGUTB-CWEJAESISA-N NC=1SC=C(N1)/C(/C(=O)N[C@H]1C(N(C1=O)O)(C)C)=N/OCCOC1=CC=C(C=C1)C(NCCNC=N)=N Chemical compound NC=1SC=C(N1)/C(/C(=O)N[C@H]1C(N(C1=O)O)(C)C)=N/OCCOC1=CC=C(C=C1)C(NCCNC=N)=N NYNWPBAFYJGUTB-CWEJAESISA-N 0.000 claims description 2
• HRXVAIQXRXNRJT-VLKICEKPSA-N O=C1N(OCS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCc1ccc(C(N)=N)cc1 Chemical compound O=C1N(OCS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCc1ccc(C(N)=N)cc1 HRXVAIQXRXNRJT-VLKICEKPSA-N 0.000 claims description 2
• OQTYUNDCTQEHCJ-DBPQUTDOSA-N O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OC(CC(O)=O)COc1ccc(C(N)=N)cc1 Chemical compound O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OC(CC(O)=O)COc1ccc(C(N)=N)cc1 OQTYUNDCTQEHCJ-DBPQUTDOSA-N 0.000 claims description 2
• DTOSAZMFGAHCCB-QDXZIFQYSA-N O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCC(C(O)=O)Oc1ccc(C(N)=N)cc1 Chemical compound O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCC(C(O)=O)Oc1ccc(C(N)=N)cc1 DTOSAZMFGAHCCB-QDXZIFQYSA-N 0.000 claims description 2
• SEMDQQWPMQXTMW-FIWXLPQASA-N O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCC(C)(C)Oc1ccc(C(N)=N)cc1 Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCC(C)(C)Oc1ccc(C(N)=N)cc1 SEMDQQWPMQXTMW-FIWXLPQASA-N 0.000 claims description 2
• BLCYGQVKTALHJC-OSVZUKHBSA-N O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCCOc1cc(C(N)=N)no1 Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCCOc1cc(C(N)=N)no1 BLCYGQVKTALHJC-OSVZUKHBSA-N 0.000 claims description 2
• MMPSIEBNJKMXOF-MKAGAKJLSA-N [(2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoylphenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidin-1-yl]oxymethanesulfonic acid Chemical compound O=C1N(OCS(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1 MMPSIEBNJKMXOF-MKAGAKJLSA-N 0.000 claims description 2
• QQELDOOYSFPGBG-LMITWDTESA-N [(3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-[n'-[2-(dimethylamino)ethyl]carbamimidoyl]phenoxy]ethoxyimino]acetyl]amino]-2,2-dimethyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound C1=CC(C(N)=NCCN(C)C)=CC=C1OCCO\N=C(C=1N=C(N)SC=1)/C(=O)N[C@H]1C(C)(C)N(OS(O)(=O)=O)C1=O QQELDOOYSFPGBG-LMITWDTESA-N 0.000 claims description 2
• DKOMWZLYEIWRDV-BGYQVPDLSA-N [(3s)-3-[[(2z)-2-[2-[4-(5-amino-1,4,5,6-tetrahydropyrimidin-2-yl)phenoxy]ethoxyimino]-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-2,2-dimethyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C=2NCC(N)CN=2)C=C1 DKOMWZLYEIWRDV-BGYQVPDLSA-N 0.000 claims description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
• 230000008569 process Effects 0.000 claims description 2
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
• 239000008194 pharmaceutical composition Substances 0.000 claims 4
• 238000006467 substitution reaction Methods 0.000 claims 4
• ZJJAPZRIOYVJBX-IEGQBCMDSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoylanilino)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCNC1=CC=C(C(N)=N)C=C1 ZJJAPZRIOYVJBX-IEGQBCMDSA-N 0.000 claims 1
• FHYHFHDLQKADIP-AAGJFWKWSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoylphenyl)sulfanylethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCSC1=CC=C(C(N)=N)C=C1 FHYHFHDLQKADIP-AAGJFWKWSA-N 0.000 claims 1
• DFYQUBCQDAEGAR-DLGGPMKASA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(6-carbamimidoylpyridin-3-yl)oxyethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)N=C1 DFYQUBCQDAEGAR-DLGGPMKASA-N 0.000 claims 1
• MQRQPIRWCADKNJ-KXLHIESCSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[(4-carbamimidoylthiophen-2-yl)methoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOCC1=CC(C(N)=N)=CS1 MQRQPIRWCADKNJ-KXLHIESCSA-N 0.000 claims 1
• KGTHPNZHNFANQX-IEGQBCMDSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-(diaminomethylideneamino)phenoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(N=C(N)N)C=C1 KGTHPNZHNFANQX-IEGQBCMDSA-N 0.000 claims 1
• MMPRWBWQMNJEBU-FIWXLPQASA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[3-[4-(diaminomethylideneamino)phenoxy]propoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCCOC1=CC=C(N=C(N)N)C=C1 MMPRWBWQMNJEBU-FIWXLPQASA-N 0.000 claims 1
• VCACGBRMRUYENY-IEGQBCMDSA-N (2s,3s)-3-[[(2z)-2-[2-[4-[(z)-c-aminocarbonohydrazonoyl]phenoxy]ethoxyimino]-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(\N)=N\N)C=C1 VCACGBRMRUYENY-IEGQBCMDSA-N 0.000 claims 1
• NYBYNTFVQYHGIP-PZGASYLGSA-N [(2s,3s)-3-[[(2z)-2-[2-[4-[n'-(2-aminoethyl)carbamimidoyl]phenoxy]ethoxyimino]-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-2-methyl-4-oxoazetidin-1-yl]oxymethanesulfonic acid Chemical compound O=C1N(OCS(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=NCCN)C=C1 NYBYNTFVQYHGIP-PZGASYLGSA-N 0.000 claims 1
• KLGJYSTYTMQDOO-IUMFXXMVSA-N [(3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-[n'-[(3s)-1-ethanimidoylpyrrolidin-3-yl]carbamimidoyl]phenoxy]ethoxyimino]acetyl]amino]-2,2-dimethyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound C1N(C(=N)C)CC[C@@H]1N=C(N)C(C=C1)=CC=C1OCCO\N=C(C=1N=C(N)SC=1)/C(=O)N[C@H]1C(C)(C)N(OS(O)(=O)=O)C1=O KLGJYSTYTMQDOO-IUMFXXMVSA-N 0.000 claims 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
• 238000002560 therapeutic procedure Methods 0.000 claims 1
• 238000005481 NMR spectroscopy Methods 0.000 description 306
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 280
• 239000000203 mixture Substances 0.000 description 260
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 255
• 239000000243 solution Substances 0.000 description 219
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 175
• 239000007787 solid Substances 0.000 description 168
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 159
• 238000004128 high performance liquid chromatography Methods 0.000 description 125
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 107
• 235000019439 ethyl acetate Nutrition 0.000 description 95
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 89
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 87
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 79
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 76
• 238000004440 column chromatography Methods 0.000 description 69
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
• 239000000706 filtrate Substances 0.000 description 66
• 239000011541 reaction mixture Substances 0.000 description 66
• 238000005259 measurement Methods 0.000 description 65
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 64
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 51
• 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 50
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 49
• 239000000047 product Substances 0.000 description 48
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 47
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 42
• 229910052938 sodium sulfate Inorganic materials 0.000 description 41
• 235000011152 sodium sulphate Nutrition 0.000 description 41
• 239000000725 suspension Substances 0.000 description 39
• 238000001914 filtration Methods 0.000 description 37
• 238000000746 purification Methods 0.000 description 36
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
• 238000003756 stirring Methods 0.000 description 34
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 34
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
• 230000002829 reductive effect Effects 0.000 description 31
• 239000003921 oil Substances 0.000 description 30
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 28
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 28
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
• 239000012267 brine Substances 0.000 description 27
• 239000000284 extract Substances 0.000 description 27
• 239000002904 solvent Substances 0.000 description 26
• 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 25
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 25
• 239000010410 layer Substances 0.000 description 23
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 22
• 239000002244 precipitate Substances 0.000 description 22
• 0 C*C(N(*)*)=N* Chemical compound C*C(N(*)*)=N* 0.000 description 21
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
• 238000006243 chemical reaction Methods 0.000 description 21
• 229910000027 potassium carbonate Inorganic materials 0.000 description 21
• 235000011181 potassium carbonates Nutrition 0.000 description 21
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
• CFMZSMGAMPBRBE-UHFFFAOYSA-N 2-hydroxyisoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(O)C(=O)C2=C1 CFMZSMGAMPBRBE-UHFFFAOYSA-N 0.000 description 19
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
• 239000012043 crude product Substances 0.000 description 19
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 17
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
• 208000015181 infectious disease Diseases 0.000 description 16
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 15
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
• 229910021529 ammonia Inorganic materials 0.000 description 14
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 14
• 229920006395 saturated elastomer Polymers 0.000 description 14
• 239000011734 sodium Substances 0.000 description 14
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 13
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 13
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 13
• VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 13
• 229960000583 acetic acid Drugs 0.000 description 12
• 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 11
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 11
• 238000001816 cooling Methods 0.000 description 11
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 11
• 239000006260 foam Substances 0.000 description 11
• 235000019253 formic acid Nutrition 0.000 description 11
• 150000002431 hydrogen Chemical class 0.000 description 11
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• 229910052708 sodium Inorganic materials 0.000 description 11
• 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 10
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
• 235000019270 ammonium chloride Nutrition 0.000 description 10
• 229960001701 chloroform Drugs 0.000 description 10
• 239000007789 gas Substances 0.000 description 10
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 9
• 241000588724 Escherichia coli Species 0.000 description 9
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
• 238000004587 chromatography analysis Methods 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 239000007788 liquid Substances 0.000 description 9
• 229910000104 sodium hydride Inorganic materials 0.000 description 9
• 241000699670 Mus sp. Species 0.000 description 8
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
• WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical class O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 239000012312 sodium hydride Substances 0.000 description 8
• 238000004809 thin layer chromatography Methods 0.000 description 8
• 239000003643 water by type Substances 0.000 description 8
• CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 7
• 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 7
• 229930195725 Mannitol Natural products 0.000 description 7
• 229960003644 aztreonam Drugs 0.000 description 7
• 230000015572 biosynthetic process Effects 0.000 description 7
• 125000004093 cyano group Chemical group *C#N 0.000 description 7
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 7
• 239000000594 mannitol Substances 0.000 description 7
• 235000010355 mannitol Nutrition 0.000 description 7
• 239000000843 powder Substances 0.000 description 7
• 239000003586 protic polar solvent Substances 0.000 description 7
• BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 7
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 6
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical class NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical class CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 150000001409 amidines Chemical group 0.000 description 6
• 238000001704 evaporation Methods 0.000 description 6
• 230000008020 evaporation Effects 0.000 description 6
• 239000005457 ice water Substances 0.000 description 6
• 239000002480 mineral oil Substances 0.000 description 6
• 235000010446 mineral oil Nutrition 0.000 description 6
• 125000006413 ring segment Chemical group 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 6
• QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 6
• PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 5
• XDBZJXRPEKFIFR-UHFFFAOYSA-N 2-(oxan-2-yloxy)ethanol Chemical compound OCCOC1CCCCO1 XDBZJXRPEKFIFR-UHFFFAOYSA-N 0.000 description 5
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
• 241000699666 Mus <mouse, genus> Species 0.000 description 5
• 206010035664 Pneumonia Diseases 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 230000000844 anti-bacterial effect Effects 0.000 description 5
• 239000002585 base Substances 0.000 description 5
• 230000003115 biocidal effect Effects 0.000 description 5
• 239000012141 concentrate Substances 0.000 description 5
• 238000005859 coupling reaction Methods 0.000 description 5
• SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 5
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
• UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 5
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 230000029936 alkylation Effects 0.000 description 4
• 238000005804 alkylation reaction Methods 0.000 description 4
• 239000000010 aprotic solvent Substances 0.000 description 4
• 102000006635 beta-lactamase Human genes 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000012230 colorless oil Substances 0.000 description 4
• 230000008878 coupling Effects 0.000 description 4
• 238000010168 coupling process Methods 0.000 description 4
• 238000010511 deprotection reaction Methods 0.000 description 4
• FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
• 230000002401 inhibitory effect Effects 0.000 description 4
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
• DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 4
• 229960002260 meropenem Drugs 0.000 description 4
• 244000052769 pathogen Species 0.000 description 4
• 229910000029 sodium carbonate Inorganic materials 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• LZRDHSFPLUWYAX-UHFFFAOYSA-N tert-butyl 4-aminopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1 LZRDHSFPLUWYAX-UHFFFAOYSA-N 0.000 description 4
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
• 150000003952 β-lactams Chemical class 0.000 description 4
• DOSUQMBAMQLTFF-UHFFFAOYSA-N 2-(2-hydroxyethoxy)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(OCCO)C(=O)C2=C1 DOSUQMBAMQLTFF-UHFFFAOYSA-N 0.000 description 3
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
• AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 3
• IESAZIXNZFEEFQ-UHFFFAOYSA-N 5-(hydroxymethyl)thiophene-3-carbonitrile Chemical compound OCC1=CC(C#N)=CS1 IESAZIXNZFEEFQ-UHFFFAOYSA-N 0.000 description 3
• YUEKWNYGXNDQRO-UHFFFAOYSA-N 5-hydroxypyridine-2-carbonitrile Chemical compound OC1=CC=C(C#N)N=C1 YUEKWNYGXNDQRO-UHFFFAOYSA-N 0.000 description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 241000589291 Acinetobacter Species 0.000 description 3
• 244000034356 Aframomum angustifolium Species 0.000 description 3
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
• WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 3
• DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 3
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 3
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
• 125000003277 amino group Chemical group 0.000 description 3
• 235000011114 ammonium hydroxide Nutrition 0.000 description 3
• 230000001580 bacterial effect Effects 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 229940079593 drug Drugs 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• LSGWSXRILNPXKJ-UHFFFAOYSA-N ethyl oxirane-2-carboxylate Chemical compound CCOC(=O)C1CO1 LSGWSXRILNPXKJ-UHFFFAOYSA-N 0.000 description 3
• 238000003818 flash chromatography Methods 0.000 description 3
• 238000009472 formulation Methods 0.000 description 3
• VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• 238000010253 intravenous injection Methods 0.000 description 3
• 150000007530 organic bases Chemical class 0.000 description 3
• 239000012074 organic phase Substances 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• 206010034674 peritonitis Diseases 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 238000002953 preparative HPLC Methods 0.000 description 3
• 238000000926 separation method Methods 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 239000007858 starting material Substances 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 125000003396 thiol group Chemical group [H]S* 0.000 description 3
• VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 2
• PXZNJHHUYJRFPZ-UHFFFAOYSA-N (4-bromothiophen-2-yl)methanol Chemical compound OCC1=CC(Br)=CS1 PXZNJHHUYJRFPZ-UHFFFAOYSA-N 0.000 description 2
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
• FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
• BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical compound OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 2
• PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
• SMEKVRWNFODGJB-UHFFFAOYSA-N 2-[2-(oxan-2-yloxy)ethoxy]-1,3-thiazole-4-carbonitrile Chemical compound N#CC1=CSC(OCCOC2OCCCC2)=N1 SMEKVRWNFODGJB-UHFFFAOYSA-N 0.000 description 2
• HJFVNYQLHDFCIE-UHFFFAOYSA-N 2-[2-(oxan-2-yloxy)ethoxy]-1,3-thiazole-4-carboxamide Chemical compound NC(=O)C1=CSC(OCCOC2OCCCC2)=N1 HJFVNYQLHDFCIE-UHFFFAOYSA-N 0.000 description 2
• AHKIFHQVVULEBK-UHFFFAOYSA-N 2-[2-(oxan-2-yloxy)ethoxy]-1,3-thiazole-4-carboximidamide Chemical compound NC(=N)C1=CSC(OCCOC2OCCCC2)=N1 AHKIFHQVVULEBK-UHFFFAOYSA-N 0.000 description 2
• QYKMXOQBSUGIQR-UHFFFAOYSA-N 2-[2-(oxan-2-yloxy)ethoxy]-1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC(OCCOC2OCCCC2)=N1 QYKMXOQBSUGIQR-UHFFFAOYSA-N 0.000 description 2
• KBCQZHYVUVQTOU-UHFFFAOYSA-N 2-[5-chloro-2-(tritylamino)-1,3-thiazol-4-yl]-2-oxoacetic acid Chemical compound S1C(Cl)=C(C(=O)C(=O)O)N=C1NC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 KBCQZHYVUVQTOU-UHFFFAOYSA-N 0.000 description 2
• VFGXWMIHKUTIGO-UHFFFAOYSA-N 2-fluoro-4-(oxan-2-yloxy)benzonitrile Chemical compound C1=C(C#N)C(F)=CC(OC2OCCCC2)=C1 VFGXWMIHKUTIGO-UHFFFAOYSA-N 0.000 description 2
• REIVHYDACHXPNH-UHFFFAOYSA-N 2-fluoro-4-hydroxybenzonitrile Chemical compound OC1=CC=C(C#N)C(F)=C1 REIVHYDACHXPNH-UHFFFAOYSA-N 0.000 description 2
• APVQPLLKGLULDW-UHFFFAOYSA-N 2-hydroxy-3-[4-[(e)-n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenoxy]propanoic acid Chemical compound CC(C)(C)OC(=O)\N=C(\N)C1=CC=C(OCC(O)C(O)=O)C=C1 APVQPLLKGLULDW-UHFFFAOYSA-N 0.000 description 2
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 2
• PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 2
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical class C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 2
• MLSBNQDVLBGYNM-UHFFFAOYSA-N 3,5-bis[(propan-2-ylideneamino)oxy]pyridine-2-carbonitrile Chemical compound CC(C)=NOC1=CN=C(C#N)C(ON=C(C)C)=C1 MLSBNQDVLBGYNM-UHFFFAOYSA-N 0.000 description 2
• RUQATSBFFHGGLO-UHFFFAOYSA-N 3,5-dihydroxypyridine-2-carboximidamide Chemical compound NC(=N)c1ncc(O)cc1O RUQATSBFFHGGLO-UHFFFAOYSA-N 0.000 description 2
• NIBIXUAJKNXVER-UHFFFAOYSA-N 3-amino-4-(2-aminooxyethoxy)benzenecarboximidamide Chemical compound NOCCOC1=CC=C(C(N)=N)C=C1N NIBIXUAJKNXVER-UHFFFAOYSA-N 0.000 description 2
• VWBGLXZWGDKMJI-UHFFFAOYSA-N 3-amino-4-(2-aminooxyethoxy)benzonitrile Chemical compound NOCCOC1=CC=C(C#N)C=C1N VWBGLXZWGDKMJI-UHFFFAOYSA-N 0.000 description 2
• XMJAZRAGSPODRO-UHFFFAOYSA-N 4-(2-aminooxy-2-methylpropoxy)benzenecarboximidamide Chemical compound NOC(C)(C)COC1=CC=C(C(N)=N)C=C1 XMJAZRAGSPODRO-UHFFFAOYSA-N 0.000 description 2
• IKTBRGPFDOGEHF-UHFFFAOYSA-N 4-(2-aminooxyethoxy)benzonitrile Chemical compound NOCCOC1=CC=C(C#N)C=C1 IKTBRGPFDOGEHF-UHFFFAOYSA-N 0.000 description 2
• OEQDAXJMTSOEAG-UHFFFAOYSA-N 4-(2-bromoethoxy)-3-(hydroxymethyl)benzonitrile Chemical compound OCC1=CC(C#N)=CC=C1OCCBr OEQDAXJMTSOEAG-UHFFFAOYSA-N 0.000 description 2
• IVKAPFWKLFIYCG-UHFFFAOYSA-N 4-(2-bromoethoxy)benzonitrile Chemical compound BrCCOC1=CC=C(C#N)C=C1 IVKAPFWKLFIYCG-UHFFFAOYSA-N 0.000 description 2
• FUDUCMYJPLOGEK-UHFFFAOYSA-N 4-(2-hydroxyethoxy)-3-nitrobenzonitrile Chemical compound OCCOC1=CC=C(C#N)C=C1[N+]([O-])=O FUDUCMYJPLOGEK-UHFFFAOYSA-N 0.000 description 2
• DYEZRXLVZMZHQT-UHFFFAOYSA-N 4-chloropyridine-2-carbonitrile Chemical compound ClC1=CC=NC(C#N)=C1 DYEZRXLVZMZHQT-UHFFFAOYSA-N 0.000 description 2
• XAASLEJRGFPHEV-UHFFFAOYSA-N 4-cyanobenzyl alcohol Chemical compound OCC1=CC=C(C#N)C=C1 XAASLEJRGFPHEV-UHFFFAOYSA-N 0.000 description 2
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
• LZIHICWURCDAKA-UHFFFAOYSA-N 5-(2-hydroxyethoxymethyl)thiophene-3-carbonitrile Chemical compound OCCOCC1=CC(C#N)=CS1 LZIHICWURCDAKA-UHFFFAOYSA-N 0.000 description 2
• PFHFDZCJGDWQGF-UHFFFAOYSA-N 5-(bromomethyl)thiophene-3-carbonitrile Chemical compound BrCC1=CC(C#N)=CS1 PFHFDZCJGDWQGF-UHFFFAOYSA-N 0.000 description 2
• QCMAVAYMVZWIIZ-UHFFFAOYSA-N 6-(2-hydroxyethoxy)pyridazine-3-carboximidamide Chemical compound NC(=N)C1=CC=C(OCCO)N=N1 QCMAVAYMVZWIIZ-UHFFFAOYSA-N 0.000 description 2
• SPAPEMGSMUESHB-UHFFFAOYSA-N 6-(oxan-2-yloxy)-1,2-benzoxazol-3-amine Chemical compound C=1C=C2C(N)=NOC2=CC=1OC1CCCCO1 SPAPEMGSMUESHB-UHFFFAOYSA-N 0.000 description 2
• NTDISTIQLNPEDF-UHFFFAOYSA-N 6-fluoropyridazine-3-carbonitrile Chemical compound FC1=CC=C(C#N)N=N1 NTDISTIQLNPEDF-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• 241000607534 Aeromonas Species 0.000 description 2
• 229920001817 Agar Polymers 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• 241000606124 Bacteroides fragilis Species 0.000 description 2
• 241001214789 Basilea Species 0.000 description 2
• KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
• 108020004256 Beta-lactamase Proteins 0.000 description 2
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 241000588919 Citrobacter freundii Species 0.000 description 2
• HFOCASGSCGXXGN-UHFFFAOYSA-N Cl.OCCOC=1SC=C(N1)C(=N)N Chemical compound Cl.OCCOC=1SC=C(N1)C(=N)N HFOCASGSCGXXGN-UHFFFAOYSA-N 0.000 description 2
• 241000193468 Clostridium perfringens Species 0.000 description 2
• 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
• 108090000204 Dipeptidase 1 Proteins 0.000 description 2
• 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
• 241000588697 Enterobacter cloacae Species 0.000 description 2
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical class NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 2
• 241000192125 Firmicutes Species 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 2
• 241000287828 Gallus gallus Species 0.000 description 2
• 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 2
• 241000606790 Haemophilus Species 0.000 description 2
• 241000606768 Haemophilus influenzae Species 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
• 239000003810 Jones reagent Substances 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• 208000032376 Lung infection Diseases 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 201000009906 Meningitis Diseases 0.000 description 2
• 241000588655 Moraxella catarrhalis Species 0.000 description 2
• 241000588772 Morganella morganii Species 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• 150000001204 N-oxides Chemical class 0.000 description 2
• 241001494479 Pecora Species 0.000 description 2
• 241000286209 Phasianidae Species 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• 241001240958 Pseudomonas aeruginosa PAO1 Species 0.000 description 2
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
• 241000607768 Shigella Species 0.000 description 2
• 239000000589 Siderophore Substances 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• 241000122973 Stenotrophomonas maltophilia Species 0.000 description 2
• 241000194017 Streptococcus Species 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• 208000009470 Ventilator-Associated Pneumonia Diseases 0.000 description 2
• ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 2
• 239000012346 acetyl chloride Substances 0.000 description 2
• 239000008272 agar Substances 0.000 description 2
• 229940024606 amino acid Drugs 0.000 description 2
• 235000001014 amino acid Nutrition 0.000 description 2
• 150000001413 amino acids Chemical class 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 239000012223 aqueous fraction Substances 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 239000012298 atmosphere Substances 0.000 description 2
• PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 2
• MTJXQSUHERULAM-UHFFFAOYSA-N benzhydryl 2-aminooxy-3-[4-[n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenoxy]propanoate Chemical compound C1=CC(C(N)=NC(=O)OC(C)(C)C)=CC=C1OCC(ON)C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 MTJXQSUHERULAM-UHFFFAOYSA-N 0.000 description 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 2
• RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 2
• KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical class NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 244000309464 bull Species 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 239000002775 capsule Substances 0.000 description 2
• 150000001718 carbodiimides Chemical class 0.000 description 2
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
• 235000013330 chicken meat Nutrition 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 230000001332 colony forming effect Effects 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical class NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
• BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 208000001848 dysentery Diseases 0.000 description 2
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
• GBIVJROKWFCOGF-LLVKDONJSA-N ethyl (2r)-3-(4-cyanophenoxy)-2-hydroxypropanoate Chemical compound CCOC(=O)[C@H](O)COC1=CC=C(C#N)C=C1 GBIVJROKWFCOGF-LLVKDONJSA-N 0.000 description 2
• CNHISCQPKKGDPO-UHFFFAOYSA-N ethyl 2-bromo-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(Br)=N1 CNHISCQPKKGDPO-UHFFFAOYSA-N 0.000 description 2
• GBIVJROKWFCOGF-UHFFFAOYSA-N ethyl 3-(4-cyanophenoxy)-2-hydroxypropanoate Chemical compound CCOC(=O)C(O)COC1=CC=C(C#N)C=C1 GBIVJROKWFCOGF-UHFFFAOYSA-N 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 229960001031 glucose Drugs 0.000 description 2
• 239000008103 glucose Substances 0.000 description 2
• 229960002449 glycine Drugs 0.000 description 2
• 244000000058 gram-negative pathogen Species 0.000 description 2
• 238000005984 hydrogenation reaction Methods 0.000 description 2
• 239000007943 implant Substances 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 238000011065 in-situ storage Methods 0.000 description 2
• 239000003456 ion exchange resin Substances 0.000 description 2
• 229920003303 ion-exchange polymer Polymers 0.000 description 2
• 150000002500 ions Chemical class 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• JBWMSSZODZMFQS-UHFFFAOYSA-N methyl 2-hydroxy-3-[4-(C-methoxycarbonimidoyl)phenoxy]propanoate hydrochloride Chemical compound Cl.COC(=O)C(O)COc1ccc(cc1)C(=N)OC JBWMSSZODZMFQS-UHFFFAOYSA-N 0.000 description 2
• AUEHXQGWXCMTDP-UHFFFAOYSA-N methyl 2-hydroxy-3-[4-[(e)-n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenoxy]propanoate Chemical compound COC(=O)C(O)COC1=CC=C(C(\N)=N/C(=O)OC(C)(C)C)C=C1 AUEHXQGWXCMTDP-UHFFFAOYSA-N 0.000 description 2
• HLSZIRZWJFKFLI-UHFFFAOYSA-N methyl 3-(4-carbamimidoylphenoxy)-2-hydroxypropanoate Chemical compound COC(=O)C(O)COC1=CC=C(C(N)=N)C=C1 HLSZIRZWJFKFLI-UHFFFAOYSA-N 0.000 description 2
• YYDUTFIJZWKQDE-UHFFFAOYSA-N methyl 3-amino-4-(2-aminooxyethoxy)benzenecarboximidate dihydrochloride Chemical compound Cl.Cl.COC(=N)c1ccc(OCCON)c(N)c1 YYDUTFIJZWKQDE-UHFFFAOYSA-N 0.000 description 2
• 239000002808 molecular sieve Substances 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
• 235000019796 monopotassium phosphate Nutrition 0.000 description 2
• YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 2
• LFLHFZUUDOITRN-UHFFFAOYSA-N o-[2-[4-(4,5-dihydro-1h-imidazol-2-yl)phenoxy]ethyl]hydroxylamine Chemical compound C1=CC(OCCON)=CC=C1C1=NCCN1 LFLHFZUUDOITRN-UHFFFAOYSA-N 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• 150000002923 oximes Chemical class 0.000 description 2
• 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 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
• 239000002798 polar solvent Substances 0.000 description 2
• 229920001467 poly(styrenesulfonates) Polymers 0.000 description 2
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
• VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 2
• 229940090181 propyl acetate Drugs 0.000 description 2
• 230000001681 protective effect Effects 0.000 description 2
• 230000005180 public health Effects 0.000 description 2
• GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 2
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Chemical class C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• 239000002002 slurry Substances 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
• 239000011877 solvent mixture Substances 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• INHZLFNDJHETRT-UHFFFAOYSA-N tert-butyl (NE)-N-[amino-[5-(2-aminooxyethoxy)-3-hydroxypyridin-2-yl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)NC(=N)c1ncc(OCCON)cc1O INHZLFNDJHETRT-UHFFFAOYSA-N 0.000 description 2
• ZFTGGWRFJVLVLJ-UHFFFAOYSA-N tert-butyl (ne)-n-[amino-[4-(3-amino-2-aminooxy-3-oxopropoxy)phenyl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)\N=C(\N)C1=CC=C(OCC(ON)C(N)=O)C=C1 ZFTGGWRFJVLVLJ-UHFFFAOYSA-N 0.000 description 2
• UYFUNQSLBJKZAG-UHFFFAOYSA-N tert-butyl (nz)-n-[amino-[2-(2-aminooxyethoxy)-1,3-thiazol-4-yl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)\N=C(/N)C1=CSC(OCCON)=N1 UYFUNQSLBJKZAG-UHFFFAOYSA-N 0.000 description 2
• CVEOSYHCYWACKD-UHFFFAOYSA-N tert-butyl N-[amino-[2-[2-(1,3-dioxoisoindol-2-yl)oxyethoxy]-1,3-thiazol-4-yl]methylidene]carbamate Chemical compound C1(=O)C2=CC=CC=C2C(=O)N1OCCOC1=NC(=CS1)C(=N)NC(=O)OC(C)(C)C CVEOSYHCYWACKD-UHFFFAOYSA-N 0.000 description 2
• AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 2
• DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 2
• HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 2
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
• ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• JKCKRNYECSTMLV-UHFFFAOYSA-N thiophene-3-carboximidamide Chemical compound NC(=N)C=1C=CSC=1 JKCKRNYECSTMLV-UHFFFAOYSA-N 0.000 description 2
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
• 208000019206 urinary tract infection Diseases 0.000 description 2
• DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
• TXLBWGHHWWGTBU-MRXNPFEDSA-N (2r)-2-hydroxy-3-[4-[n'-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]carbamimidoyl]phenoxy]propanoic acid Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N=C(N)C1=CC=C(OC[C@@H](O)C(O)=O)C=C1 TXLBWGHHWWGTBU-MRXNPFEDSA-N 0.000 description 1
• ISUIVWNWEDIHJD-GBXIJSLDSA-N (2r,3s)-3-azaniumyl-2-methyl-4-oxoazetidine-1-sulfonate Chemical compound C[C@@H]1[C@H](N)C(=O)N1S(O)(=O)=O ISUIVWNWEDIHJD-GBXIJSLDSA-N 0.000 description 1
• OSNSWKAZFASRNG-WNFIKIDCSA-N (2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol;hydrate Chemical compound O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O OSNSWKAZFASRNG-WNFIKIDCSA-N 0.000 description 1
• ZDWQZOLSJSBMEM-KXLHIESCSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(4-carbamimidoylphenyl)methoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCC1=CC=C(C(N)=N)C=C1 ZDWQZOLSJSBMEM-KXLHIESCSA-N 0.000 description 1
• XETHAHFSRGGEIN-OQMYIJJMSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoyl-2-chlorophenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1Cl XETHAHFSRGGEIN-OQMYIJJMSA-N 0.000 description 1
• UGTLYPYZRIEXBG-OQMYIJJMSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-(4-carbamimidoyl-2-fluorophenoxy)ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1F UGTLYPYZRIEXBG-OQMYIJJMSA-N 0.000 description 1
• OSWWZHFQGVDOPP-IKGNQYEOSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[(5-carbamimidoyl-1,3,4-thiadiazol-2-yl)oxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=NN=C(C(N)=N)S1 OSWWZHFQGVDOPP-IKGNQYEOSA-N 0.000 description 1
• ZYRXZIYKRTWEKX-MKAGAKJLSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-(n'-methylcarbamimidoyl)phenoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound C1=CC(C(N)=NC)=CC=C1OCCO\N=C(C=1N=C(N)SC=1)/C(=O)N[C@@H]1C(=O)N(S(O)(=O)=O)[C@H]1C ZYRXZIYKRTWEKX-MKAGAKJLSA-N 0.000 description 1
• WKVQJAQWVFWIFY-IJNVIVFESA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-(n'-propan-2-ylcarbamimidoyl)phenoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound C1=CC(C(N)=NC(C)C)=CC=C1OCCO\N=C(C=1N=C(N)SC=1)/C(=O)N[C@@H]1C(=O)N(S(O)(=O)=O)[C@H]1C WKVQJAQWVFWIFY-IJNVIVFESA-N 0.000 description 1
• DQCZMZSVMVBQJP-FIWXLPQASA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-[(z)-n'-formamidocarbamimidoyl]phenoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(\N)=N\NC=O)C=C1 DQCZMZSVMVBQJP-FIWXLPQASA-N 0.000 description 1
• VGVNTWMZHJDLPQ-ZIPFDZITSA-N (2s,3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-carbamimidoyl-2-(hydroxymethyl)phenoxy]ethoxyimino]acetyl]amino]-2-methyl-4-oxoazetidine-1-sulfonic acid Chemical compound O=C1N(S(O)(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N)C=C1CO VGVNTWMZHJDLPQ-ZIPFDZITSA-N 0.000 description 1
• ISUIVWNWEDIHJD-HRFVKAFMSA-N (2s,3s)-3-azaniumyl-2-methyl-4-oxoazetidine-1-sulfonate Chemical compound C[C@H]1[C@H](N)C(=O)N1S(O)(=O)=O ISUIVWNWEDIHJD-HRFVKAFMSA-N 0.000 description 1
• BNUZJZIJJYSNRA-UHFFFAOYSA-N (3-amino-2-oxo-1-azaspiro[3.4]octan-1-yl) hydrogen sulfate Chemical compound NC1C(=O)N(OS(O)(=O)=O)C11CCCC1 BNUZJZIJJYSNRA-UHFFFAOYSA-N 0.000 description 1
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• QUKGLNCXGVWCJX-UHFFFAOYSA-N 1,3,4-thiadiazol-2-amine Chemical compound NC1=NN=CS1 QUKGLNCXGVWCJX-UHFFFAOYSA-N 0.000 description 1
• VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
• RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical compound NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
• OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 description 1
• OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
• NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
• FYJOJJPFWAMBJU-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)oxy-3-[4-[(Z)-N'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenoxy]propanoic acid Chemical compound C1=CC(C(/N)=N/C(=O)OC(C)(C)C)=CC=C1OCC(C(O)=O)ON1C(=O)C2=CC=CC=C2C1=O FYJOJJPFWAMBJU-UHFFFAOYSA-N 0.000 description 1
• IDHGAUQXGVVVNE-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)oxyethyl methanesulfonate Chemical compound C1=CC=C2C(=O)N(OCCOS(=O)(=O)C)C(=O)C2=C1 IDHGAUQXGVVVNE-UHFFFAOYSA-N 0.000 description 1
• WOXFMYVTSLAQMO-UHFFFAOYSA-N 2-Pyridinemethanamine Chemical compound NCC1=CC=CC=N1 WOXFMYVTSLAQMO-UHFFFAOYSA-N 0.000 description 1
• VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 1
• SYSDTUXAHIKTRD-UHFFFAOYSA-N 2-[(3-amino-1,2-benzoxazol-6-yl)oxy]ethanol Chemical compound OCCOC1=CC=C2C(N)=NOC2=C1 SYSDTUXAHIKTRD-UHFFFAOYSA-N 0.000 description 1
• UJORPFQWUKFXIE-UHFFFAOYSA-N 2-[1-[(4-ethoxy-2,6-difluorophenyl)methyl]-5,6-dihydro-4h-cyclopenta[c]pyrazol-3-yl]-5-methoxy-n-pyridin-4-ylpyrimidin-4-amine Chemical compound FC1=CC(OCC)=CC(F)=C1CN1C(CCC2)=C2C(C=2N=C(NC=3C=CN=CC=3)C(OC)=CN=2)=N1 UJORPFQWUKFXIE-UHFFFAOYSA-N 0.000 description 1
• DBTRPVCSUVWNKQ-UHFFFAOYSA-N 2-[2-(4-aminophenoxy)ethoxy]isoindole-1,3-dione Chemical compound C1=CC(N)=CC=C1OCCON1C(=O)C2=CC=CC=C2C1=O DBTRPVCSUVWNKQ-UHFFFAOYSA-N 0.000 description 1
• YHMZKBZQZGAGOE-UHFFFAOYSA-N 2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acid Chemical compound OC(=O)CC1=CSC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 YHMZKBZQZGAGOE-UHFFFAOYSA-N 0.000 description 1
• JPQCZOUBLNGLCZ-UHFFFAOYSA-N 2-[5-[(2-methylpropan-2-yl)oxycarbonylamino]-1,2,4-thiadiazol-3-yl]-2-oxoacetic acid Chemical compound CC(C)(C)OC(=O)NC1=NC(C(=O)C(O)=O)=NS1 JPQCZOUBLNGLCZ-UHFFFAOYSA-N 0.000 description 1
• LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 description 1
• QRXBTPFMCTXCRD-UHFFFAOYSA-N 2-chloropyridine-4-carbonitrile Chemical compound ClC1=CC(C#N)=CC=N1 QRXBTPFMCTXCRD-UHFFFAOYSA-N 0.000 description 1
• YDTVKCOARXOARR-UHFFFAOYSA-N 2-fluoro-4-(2-hydroxyethoxy)benzonitrile Chemical compound OCCOC1=CC=C(C#N)C(F)=C1 YDTVKCOARXOARR-UHFFFAOYSA-N 0.000 description 1
• OEIPIJFGEGNECW-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)benzenecarboximidamide Chemical compound NC(=N)c1ccc(OCCO)cc1O OEIPIJFGEGNECW-UHFFFAOYSA-N 0.000 description 1
• CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
• WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• RYBXYKIHANPAPY-UHFFFAOYSA-N 3,4-dihydroxybutyl acetate Chemical compound CC(=O)OCCC(O)CO RYBXYKIHANPAPY-UHFFFAOYSA-N 0.000 description 1
• YNETWPPINUSGQX-UHFFFAOYSA-N 3-(4-carbamimidoyl-3-hydroxyphenoxy)-2-hydroxypropanoic acid Chemical compound C(N)(=N)C1=C(C=C(OCC(C(=O)O)O)C=C1)O YNETWPPINUSGQX-UHFFFAOYSA-N 0.000 description 1
• KSQDQNLYKKOXHQ-UHFFFAOYSA-N 3-[(3-amino-1,2-benzoxazol-6-yl)oxy]-2-hydroxypropanoic acid Chemical compound OC(=O)C(O)COC1=CC=C2C(N)=NOC2=C1 KSQDQNLYKKOXHQ-UHFFFAOYSA-N 0.000 description 1
• KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 1
• ABYNYTFGGHVVOK-UHFFFAOYSA-N 3-amino-1,2-benzoxazol-6-ol Chemical compound OC1=CC=C2C(N)=NOC2=C1 ABYNYTFGGHVVOK-UHFFFAOYSA-N 0.000 description 1
• VZWCUYJCROJGSS-UHFFFAOYSA-N 3-amino-4-(2-hydroxyethoxy)benzonitrile Chemical compound NC1=CC(C#N)=CC=C1OCCO VZWCUYJCROJGSS-UHFFFAOYSA-N 0.000 description 1
• NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
• PHIANFGZFLCRDV-UHFFFAOYSA-N 3-formyl-4-hydroxybenzonitrile Chemical compound OC1=CC=C(C#N)C=C1C=O PHIANFGZFLCRDV-UHFFFAOYSA-N 0.000 description 1
• FODWPFQNLCOULM-UHFFFAOYSA-N 4-(1-aminooxy-2-methylpropan-2-yl)oxybenzenecarboximidamide Chemical compound NOCC(C)(C)OC1=CC=C(C(N)=N)C=C1 FODWPFQNLCOULM-UHFFFAOYSA-N 0.000 description 1
• TUCBIZDMVBRKBN-UHFFFAOYSA-N 4-(1-aminooxy-2-methylpropan-2-yl)oxybenzonitrile Chemical compound NOCC(C)(C)OC1=CC=C(C#N)C=C1 TUCBIZDMVBRKBN-UHFFFAOYSA-N 0.000 description 1
• WMNMDHIYLBCBJC-UHFFFAOYSA-N 4-(1-hydroxy-2-methylpropan-2-yl)oxybenzonitrile Chemical compound OCC(C)(C)OC1=CC=C(C#N)C=C1 WMNMDHIYLBCBJC-UHFFFAOYSA-N 0.000 description 1
• AHUPHBKVCGBDLV-UHFFFAOYSA-N 4-(2,3-dihydroxypropoxy)benzenecarboximidamide Chemical compound NC(=N)C1=CC=C(OCC(O)CO)C=C1 AHUPHBKVCGBDLV-UHFFFAOYSA-N 0.000 description 1
• UOEBTAUBLYXWSU-UHFFFAOYSA-N 4-(2-aminooxy-1,1-dimethoxyethoxy)benzenecarboximidamide Chemical compound NOCC(OC1=CC=C(C(=N)N)C=C1)(OC)OC UOEBTAUBLYXWSU-UHFFFAOYSA-N 0.000 description 1
• FFECICSIEWAXST-UHFFFAOYSA-N 4-(2-aminooxyethoxy)-2-hydroxybenzenecarboximidamide Chemical compound NOCCOC1=CC(=C(C=C1)C(N)=N)O FFECICSIEWAXST-UHFFFAOYSA-N 0.000 description 1
• WMNGDRHOVDVFAK-UHFFFAOYSA-N 4-(2-aminooxyethoxy)-2-methylbenzenecarboximidamide Chemical compound CC1=CC(OCCON)=CC=C1C(N)=N WMNGDRHOVDVFAK-UHFFFAOYSA-N 0.000 description 1
• HZRWUBPMHDNUJZ-UHFFFAOYSA-N 4-(2-aminooxyethoxy)-5-methyl-1,3-thiazole-2-carboximidamide Chemical compound CC=1SC(C(N)=N)=NC=1OCCON HZRWUBPMHDNUJZ-UHFFFAOYSA-N 0.000 description 1
• VYKHULYQQVLDCJ-UHFFFAOYSA-M 4-(2-aminooxyethoxy)-n'-[2-(1-methylpyrrolidin-1-ium-1-yl)ethyl]benzenecarboximidamide;2,2,2-trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.C=1C=C(OCCON)C=CC=1C(N)=NCC[N+]1(C)CCCC1 VYKHULYQQVLDCJ-UHFFFAOYSA-M 0.000 description 1
• GHMYBLWQZAHVSI-UHFFFAOYSA-N 4-(2-aminooxyethoxy)-n'-hydroxybenzenecarboximidamide Chemical compound NOCCOC1=CC=C(C(\N)=N\O)C=C1 GHMYBLWQZAHVSI-UHFFFAOYSA-N 0.000 description 1
• ZBGULPYOUIGQDK-UHFFFAOYSA-N 4-(2-aminooxyethoxy)-n'-methylbenzenecarboximidamide Chemical compound CN=C(N)C1=CC=C(OCCON)C=C1 ZBGULPYOUIGQDK-UHFFFAOYSA-N 0.000 description 1
• WMPVPFMBJMQIGY-UHFFFAOYSA-N 4-(2-aminooxyethylamino)benzonitrile Chemical compound NOCCNC1=CC=C(C#N)C=C1 WMPVPFMBJMQIGY-UHFFFAOYSA-N 0.000 description 1
• XTTRLWRENDRBKH-UHFFFAOYSA-N 4-(2-aminooxyethylsulfanyl)benzonitrile Chemical compound NOCCSC1=CC=C(C#N)C=C1 XTTRLWRENDRBKH-UHFFFAOYSA-N 0.000 description 1
• NATSOSGWXNNDQJ-UHFFFAOYSA-N 4-(2-bromoethoxy)-3-formylbenzonitrile Chemical compound BrCCOC1=CC=C(C#N)C=C1C=O NATSOSGWXNNDQJ-UHFFFAOYSA-N 0.000 description 1
• IISZYETXSAOZHL-UHFFFAOYSA-N 4-(2-hydroxyethoxy)-2-methylbenzonitrile Chemical compound CC1=CC(OCCO)=CC=C1C#N IISZYETXSAOZHL-UHFFFAOYSA-N 0.000 description 1
• XBGTYYYCFGIOOU-UHFFFAOYSA-N 4-(2-hydroxyethoxy)pyridine-2-carbonitrile Chemical compound OCCOC1=CC=NC(C#N)=C1 XBGTYYYCFGIOOU-UHFFFAOYSA-N 0.000 description 1
• MWBQMSRVSRVKKX-UHFFFAOYSA-N 4-(2-hydroxyethylamino)benzonitrile Chemical compound OCCNC1=CC=C(C#N)C=C1 MWBQMSRVSRVKKX-UHFFFAOYSA-N 0.000 description 1
• SDOPNFGSYJXHKK-UHFFFAOYSA-N 4-(2-hydroxyethylsulfanyl)benzonitrile Chemical compound OCCSC1=CC=C(C#N)C=C1 SDOPNFGSYJXHKK-UHFFFAOYSA-N 0.000 description 1
• ATBANLOLDZIUOW-UHFFFAOYSA-N 4-(aminooxymethyl)benzonitrile Chemical compound NOCC1=CC=C(C#N)C=C1 ATBANLOLDZIUOW-UHFFFAOYSA-N 0.000 description 1
• VRWZNQITCNBJML-UHFFFAOYSA-N 4-[(1,3-dioxoisoindol-2-yl)oxymethyl]benzonitrile Chemical compound O=C1C2=CC=CC=C2C(=O)N1OCC1=CC=C(C#N)C=C1 VRWZNQITCNBJML-UHFFFAOYSA-N 0.000 description 1
• LUGJBYZKFGQNGB-UHFFFAOYSA-N 4-[(2,2-dimethyl-1,3-dioxolan-4-yl)methoxy]benzonitrile Chemical compound O1C(C)(C)OCC1COC1=CC=C(C#N)C=C1 LUGJBYZKFGQNGB-UHFFFAOYSA-N 0.000 description 1
• JWXFJJJQXQLJHF-UHFFFAOYSA-N 4-[1-(1,3-dioxoisoindol-2-yl)oxy-2-methylpropan-2-yl]oxybenzonitrile Chemical compound O=C1C2=CC=CC=C2C(=O)N1OCC(C)(C)OC1=CC=C(C#N)C=C1 JWXFJJJQXQLJHF-UHFFFAOYSA-N 0.000 description 1
• UFWVSADHDRMXNS-UHFFFAOYSA-N 4-[2-(1,3-dioxoisoindol-2-yl)oxyethoxy]benzonitrile Chemical compound O=C1C2=CC=CC=C2C(=O)N1OCCOC1=CC=C(C#N)C=C1 UFWVSADHDRMXNS-UHFFFAOYSA-N 0.000 description 1
• LPEBMDFRIKYFCF-UHFFFAOYSA-N 4-bromo-2-methylbenzonitrile Chemical compound CC1=CC(Br)=CC=C1C#N LPEBMDFRIKYFCF-UHFFFAOYSA-N 0.000 description 1
• PDONIKHDXYHTLS-UHFFFAOYSA-N 4-bromothiophene-2-carbaldehyde Chemical compound BrC1=CSC(C=O)=C1 PDONIKHDXYHTLS-UHFFFAOYSA-N 0.000 description 1
• WWYFPDXEIFBNKE-UHFFFAOYSA-M 4-carboxybenzyl alcohol Chemical compound OCC1=CC=C(C([O-])=O)C=C1 WWYFPDXEIFBNKE-UHFFFAOYSA-M 0.000 description 1
• QXSAKPUBHTZHKW-UHFFFAOYSA-N 4-hydroxybenzamide Chemical compound NC(=O)C1=CC=C(O)C=C1 QXSAKPUBHTZHKW-UHFFFAOYSA-N 0.000 description 1
• ZVTWZSXLLMNMQC-UHFFFAOYSA-N 4-phenylmethoxybenzaldehyde Chemical compound C1=CC(C=O)=CC=C1OCC1=CC=CC=C1 ZVTWZSXLLMNMQC-UHFFFAOYSA-N 0.000 description 1
• ZGMWLWCGHMVBGD-UHFFFAOYSA-N 5-(2-aminooxyethoxy)pyridine-2-carbonitrile Chemical compound NOCCOC1=CC=C(C#N)N=C1 ZGMWLWCGHMVBGD-UHFFFAOYSA-N 0.000 description 1
• ZYXFLXVYBYCHPC-UHFFFAOYSA-N 5-(2-aminooxyethoxy)pyridine-2-carboximidamide Chemical compound NOCCOC1=CC=C(C(N)=N)N=C1 ZYXFLXVYBYCHPC-UHFFFAOYSA-N 0.000 description 1
• RGHLYXQGGDUYHQ-UHFFFAOYSA-N 5-[2-(oxan-2-yloxy)ethoxy]-1,3,4-thiadiazole-2-carbonitrile Chemical compound S1C(C#N)=NN=C1OCCOC1OCCCC1 RGHLYXQGGDUYHQ-UHFFFAOYSA-N 0.000 description 1
• QCUMCOZSVUYEDG-UHFFFAOYSA-N 5-[2-(oxan-2-yloxy)ethoxy]-1,3,4-thiadiazole-2-carboxamide Chemical compound S1C(C(=O)N)=NN=C1OCCOC1OCCCC1 QCUMCOZSVUYEDG-UHFFFAOYSA-N 0.000 description 1
• SQKVVRQXSGSGGJ-UHFFFAOYSA-N 5-[2-(oxan-2-yloxy)ethoxy]-1,3,4-thiadiazole-2-carboximidamide Chemical compound S1C(C(=N)N)=NN=C1OCCOC1OCCCC1 SQKVVRQXSGSGGJ-UHFFFAOYSA-N 0.000 description 1
• VSXVUEUQCVYVPM-UHFFFAOYSA-N 5-bromo-1,3,4-thiadiazole-2-carboxamide Chemical compound NC(=O)C1=NN=C(Br)S1 VSXVUEUQCVYVPM-UHFFFAOYSA-N 0.000 description 1
• HMURQOFNWZWERT-UHFFFAOYSA-N 5-bromo-3-fluoropyridine-2-carbonitrile Chemical compound FC1=CC(Br)=CN=C1C#N HMURQOFNWZWERT-UHFFFAOYSA-N 0.000 description 1
• GTYRFWMSDBGPTI-UHFFFAOYSA-N 5-chloropyrazine-2-carbonitrile Chemical compound ClC1=CN=C(C#N)C=N1 GTYRFWMSDBGPTI-UHFFFAOYSA-N 0.000 description 1
• JUEABELLYHFRQV-UHFFFAOYSA-N 5-fluoro-5-nitrocyclohexa-1,3-diene-1-carbonitrile Chemical compound FC1(CC(C#N)=CC=C1)[N+](=O)[O-] JUEABELLYHFRQV-UHFFFAOYSA-N 0.000 description 1
• FCECYLUEYDBZHV-UHFFFAOYSA-N 5-phenylmethoxypyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC=C1OCC1=CC=CC=C1 FCECYLUEYDBZHV-UHFFFAOYSA-N 0.000 description 1
• CNBNDPLYRXMQPE-UHFFFAOYSA-N 5-phenylmethoxypyridine-2-carboximidamide Chemical compound NC(=N)c1ccc(OCc2ccccc2)cn1 CNBNDPLYRXMQPE-UHFFFAOYSA-N 0.000 description 1
• ZPMXDLHAOZSLOK-UHFFFAOYSA-N 6-(propan-2-ylideneamino)oxy-[1,2]oxazolo[4,5-b]pyridin-3-amine Chemical compound CC(C)=NOC1=CN=C2C(N)=NOC2=C1 ZPMXDLHAOZSLOK-UHFFFAOYSA-N 0.000 description 1
• CCQUUHVUQQFTGV-UHFFFAOYSA-N 6-oxo-1h-pyridine-3-carbonitrile Chemical compound OC1=CC=C(C#N)C=N1 CCQUUHVUQQFTGV-UHFFFAOYSA-N 0.000 description 1
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 1
• CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
• 206010060921 Abdominal abscess Diseases 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• 241001673062 Achromobacter xylosoxidans Species 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 206010001076 Acute sinusitis Diseases 0.000 description 1
• 102000009027 Albumins Human genes 0.000 description 1
• 108010088751 Albumins Proteins 0.000 description 1
• 241000588986 Alcaligenes Species 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
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 206010003011 Appendicitis Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010053555 Arthritis bacterial Diseases 0.000 description 1
• 241000193830 Bacillus <bacterium> Species 0.000 description 1
• 241001148536 Bacteroides sp. Species 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 206010005940 Bone and joint infections Diseases 0.000 description 1
• 241000588807 Bordetella Species 0.000 description 1
• 241000588779 Bordetella bronchiseptica Species 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• 206010006458 Bronchitis chronic Diseases 0.000 description 1
• 241000589562 Brucella Species 0.000 description 1
• 241000589567 Brucella abortus Species 0.000 description 1
• 241001453380 Burkholderia Species 0.000 description 1
• 241000589513 Burkholderia cepacia Species 0.000 description 1
• SMZPWWZCTUBMFI-UHFFFAOYSA-N C(C1=CC=CC=C1)(C1=CC=CC=C1)OC(C(C)ON1C(C2=CC=CC=C2C1=O)=O)=O Chemical compound C(C1=CC=CC=C1)(C1=CC=CC=C1)OC(C(C)ON1C(C2=CC=CC=C2C1=O)=O)=O SMZPWWZCTUBMFI-UHFFFAOYSA-N 0.000 description 1
• QNYPQAKSVVWYLZ-UHFFFAOYSA-N CC(=O)OCCC(CO)ON1C(=O)c2ccccc2C1=O Chemical compound CC(=O)OCCC(CO)ON1C(=O)c2ccccc2C1=O QNYPQAKSVVWYLZ-UHFFFAOYSA-N 0.000 description 1
• LNGQSSQAOTYPPN-UHFFFAOYSA-N CC(C)(C)OC(=O)N(C1CCN(CC1)C(=O)OC(C)(C)C)C(=N)c1ccc(OCCON)cc1 Chemical compound CC(C)(C)OC(=O)N(C1CCN(CC1)C(=O)OC(C)(C)C)C(=N)c1ccc(OCCON)cc1 LNGQSSQAOTYPPN-UHFFFAOYSA-N 0.000 description 1
• FNYFQDKEYBJCHD-UHFFFAOYSA-N CC(C)(C)OC(=O)N1CC(CN1C(=O)OC(C)(C)C)NC(=N)c1ccc(OCCON)cc1 Chemical compound CC(C)(C)OC(=O)N1CC(CN1C(=O)OC(C)(C)C)NC(=N)c1ccc(OCCON)cc1 FNYFQDKEYBJCHD-UHFFFAOYSA-N 0.000 description 1
• DGKFSQSYGNVCAA-UHFFFAOYSA-N CCOC(=O)C=1C=C(O)N(C)N=1 Chemical compound CCOC(=O)C=1C=C(O)N(C)N=1 DGKFSQSYGNVCAA-UHFFFAOYSA-N 0.000 description 1
• BEKQZBVNTXDNEL-UHFFFAOYSA-N COC(=N)c1ccc(OC(C)(C)CON)cc1 Chemical compound COC(=N)c1ccc(OC(C)(C)CON)cc1 BEKQZBVNTXDNEL-UHFFFAOYSA-N 0.000 description 1
• 101100108294 Caenorhabditis elegans aex-5 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000589875 Campylobacter jejuni Species 0.000 description 1
• 241000282472 Canis lupus familiaris Species 0.000 description 1
• 241000283707 Capra Species 0.000 description 1
• 206010007882 Cellulitis Diseases 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
• 241000588923 Citrobacter Species 0.000 description 1
• 241000588917 Citrobacter koseri Species 0.000 description 1
• BWFOBVDDFLPFLJ-UHFFFAOYSA-N Cl.COC(=N)c1ccc(OCC(C)(C)ON)cc1 Chemical compound Cl.COC(=N)c1ccc(OCC(C)(C)ON)cc1 BWFOBVDDFLPFLJ-UHFFFAOYSA-N 0.000 description 1
• MRLWICUEAWYKKI-UHFFFAOYSA-M Cl.[Cl-].C[N+]1(CCN)CCCC1 Chemical compound Cl.[Cl-].C[N+]1(CCN)CCCC1 MRLWICUEAWYKKI-UHFFFAOYSA-M 0.000 description 1
• HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
• 241000193403 Clostridium Species 0.000 description 1
• 241000272201 Columbiformes Species 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 206010010741 Conjunctivitis Diseases 0.000 description 1
• 241000938605 Crocodylia Species 0.000 description 1
• 206010011409 Cross infection Diseases 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 1
• 229930195711 D-Serine Natural products 0.000 description 1
• 201000004624 Dermatitis Diseases 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
• 206010012742 Diarrhoea infectious Diseases 0.000 description 1
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
• 241000255925 Diptera Species 0.000 description 1
• GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
• 208000004232 Enteritis Diseases 0.000 description 1
• 241000588914 Enterobacter Species 0.000 description 1
• 241000305071 Enterobacterales Species 0.000 description 1
• 241000588921 Enterobacteriaceae Species 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• 241000588722 Escherichia Species 0.000 description 1
• 241001360526 Escherichia coli ATCC 25922 Species 0.000 description 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
• 241000400611 Eucalyptus deanei Species 0.000 description 1
• 208000001860 Eye Infections Diseases 0.000 description 1
• 241000282326 Felis catus Species 0.000 description 1
• 206010016936 Folliculitis Diseases 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 206010017964 Gastrointestinal infection Diseases 0.000 description 1
• 206010048461 Genital infection Diseases 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 241000588729 Hafnia alvei Species 0.000 description 1
• 208000008745 Healthcare-Associated Pneumonia Diseases 0.000 description 1
• 241000590002 Helicobacter pylori Species 0.000 description 1
• 241000258937 Hemiptera Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 206010021531 Impetigo Diseases 0.000 description 1
• 208000004575 Infectious Arthritis Diseases 0.000 description 1
• 206010022678 Intestinal infections Diseases 0.000 description 1
• 206010022941 Iridocyclitis Diseases 0.000 description 1
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
• 241000588748 Klebsiella Species 0.000 description 1
• 241000588915 Klebsiella aerogenes Species 0.000 description 1
• 241000588749 Klebsiella oxytoca Species 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• AYFVYJQAPQTCCC-HRFVKAFMSA-N L-allothreonine Chemical compound C[C@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-HRFVKAFMSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 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
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
• 241000589242 Legionella pneumophila Species 0.000 description 1
• 208000007764 Legionnaires' Disease Diseases 0.000 description 1
• 241000186779 Listeria monocytogenes Species 0.000 description 1
• 206010024652 Liver abscess Diseases 0.000 description 1
• 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 208000010315 Mastoiditis Diseases 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 238000006751 Mitsunobu reaction Methods 0.000 description 1
• NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
• HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical class CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
• LMFLXXVIAGRJFG-UHFFFAOYSA-N Nc1cc(ccc1OCCON1C(=O)c2ccccc2C1=O)C#N Chemical compound Nc1cc(ccc1OCCON1C(=O)c2ccccc2C1=O)C#N LMFLXXVIAGRJFG-UHFFFAOYSA-N 0.000 description 1
• 206010051606 Necrotising colitis Diseases 0.000 description 1
• 241000588653 Neisseria Species 0.000 description 1
• 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
• 241000588650 Neisseria meningitidis Species 0.000 description 1
• 206010021888 Nervous system infections Diseases 0.000 description 1
• BSGDTOPTJWWBIS-UHFFFAOYSA-N O=C1N(CCSc2ccc(cc2)C#N)C(=O)c2ccccc12 Chemical compound O=C1N(CCSc2ccc(cc2)C#N)C(=O)c2ccccc12 BSGDTOPTJWWBIS-UHFFFAOYSA-N 0.000 description 1
• COGRTXVJPVUPRF-UHFFFAOYSA-N O=C1N(OCCNc2ccc(cc2)C#N)C(=O)c2ccccc12 Chemical compound O=C1N(OCCNc2ccc(cc2)C#N)C(=O)c2ccccc12 COGRTXVJPVUPRF-UHFFFAOYSA-N 0.000 description 1
• NTYWAVPIHLAJRW-UHFFFAOYSA-N O=C1N(OCCOc2ccc(nc2)C#N)C(=O)c2ccccc12 Chemical compound O=C1N(OCCOc2ccc(nc2)C#N)C(=O)c2ccccc12 NTYWAVPIHLAJRW-UHFFFAOYSA-N 0.000 description 1
• SXLHZZPCMHMQFF-CWEJAESISA-N O=C1N(S(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCCOc1ccc(C(=N)NC2CNNC2)cc1 Chemical compound O=C1N(S(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\c1csc(N)n1)=N/OCCOc1ccc(C(=N)NC2CNNC2)cc1 SXLHZZPCMHMQFF-CWEJAESISA-N 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• 206010031252 Osteomyelitis Diseases 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
• 101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 1
• 241000606860 Pasteurella Species 0.000 description 1
• 241000606856 Pasteurella multocida Species 0.000 description 1
• 241000191992 Peptostreptococcus Species 0.000 description 1
• 241000192035 Peptostreptococcus anaerobius Species 0.000 description 1
• 201000007100 Pharyngitis Diseases 0.000 description 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
• QPFYXYFORQJZEC-FOCLMDBBSA-N Phenazopyridine Chemical compound NC1=NC(N)=CC=C1\N=N\C1=CC=CC=C1 QPFYXYFORQJZEC-FOCLMDBBSA-N 0.000 description 1
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
• 206010035723 Pneumonia moraxella Diseases 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 244000110797 Polygonum persicaria Species 0.000 description 1
• 241000605894 Porphyromonas Species 0.000 description 1
• 206010067268 Post procedural infection Diseases 0.000 description 1
• 241000605861 Prevotella Species 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 241000588769 Proteus <enterobacteria> Species 0.000 description 1
• 241000588770 Proteus mirabilis Species 0.000 description 1
• 241001472782 Proteus penneri Species 0.000 description 1
• 241000588768 Providencia Species 0.000 description 1
• 241000588777 Providencia rettgeri Species 0.000 description 1
• 241000588778 Providencia stuartii Species 0.000 description 1
• 241000589516 Pseudomonas Species 0.000 description 1
• 241001638204 Pseudophilautus stuarti Species 0.000 description 1
• 206010037596 Pyelonephritis Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 206010057190 Respiratory tract infections Diseases 0.000 description 1
• 241000282806 Rhinoceros Species 0.000 description 1
• 239000012891 Ringer solution Substances 0.000 description 1
• 241000282849 Ruminantia Species 0.000 description 1
• 241000607142 Salmonella Species 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 241000607720 Serratia Species 0.000 description 1
• 241000607715 Serratia marcescens Species 0.000 description 1
• 239000005708 Sodium hypochlorite Substances 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 206010062255 Soft tissue infection Diseases 0.000 description 1
• 241000191940 Staphylococcus Species 0.000 description 1
• 241000193985 Streptococcus agalactiae Species 0.000 description 1
• 241000193996 Streptococcus pyogenes Species 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• QYTDEUPAUMOIOP-UHFFFAOYSA-N TEMPO Chemical group CC1(C)CCCC(C)(C)N1[O] QYTDEUPAUMOIOP-UHFFFAOYSA-N 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 239000004473 Threonine Substances 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 208000037386 Typhoid Diseases 0.000 description 1
• 206010064996 Ulcerative keratitis Diseases 0.000 description 1
• 241000051616 Ulmus minor Species 0.000 description 1
• 241000607626 Vibrio cholerae Species 0.000 description 1
• 206010052428 Wound Diseases 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• 241000607734 Yersinia <bacteria> Species 0.000 description 1
• 241000607447 Yersinia enterocolitica Species 0.000 description 1
• 241000607477 Yersinia pseudotuberculosis Species 0.000 description 1
• SVKXAHPZDRANQO-GBXIJSLDSA-N [(2r,3s)-3-amino-2-methyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound C[C@@H]1[C@H](N)C(=O)N1OS(O)(=O)=O SVKXAHPZDRANQO-GBXIJSLDSA-N 0.000 description 1
• SVKXAHPZDRANQO-HRFVKAFMSA-N [(2s,3s)-3-amino-2-methyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound C[C@H]1[C@H](N)C(=O)N1OS(O)(=O)=O SVKXAHPZDRANQO-HRFVKAFMSA-N 0.000 description 1
• LSSXDMODPANJIL-IMJSIDKUSA-N [(2s,3s)-3-amino-2-methyl-4-oxoazetidin-1-yl]oxymethanesulfonic acid Chemical compound C[C@H]1[C@H](N)C(=O)N1OCS(O)(=O)=O LSSXDMODPANJIL-IMJSIDKUSA-N 0.000 description 1
• TWFRCSHLWKJBQH-UXQCFNEQSA-N [(2s,5r)-7-oxo-2-(piperidin-4-ylcarbamoyl)-1,6-diazabicyclo[3.2.1]octan-6-yl] hydrogen sulfate;hydrate Chemical compound O.O=C([C@H]1N2C[C@@H](CC1)N(C2=O)OS(=O)(=O)O)NC1CCNCC1 TWFRCSHLWKJBQH-UXQCFNEQSA-N 0.000 description 1
• JYXRWNBDPAGPRM-CWEJAESISA-N [(3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-[n'-(1,3-diaminopropan-2-yl)carbamimidoyl]phenoxy]ethoxyimino]acetyl]amino]-2,2-dimethyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=NC(CN)CN)C=C1 JYXRWNBDPAGPRM-CWEJAESISA-N 0.000 description 1
• IXUCHBUKQYYVCQ-JUMRHNHYSA-N [(3s)-3-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-[2-[4-[n'-[(3s)-pyrrolidin-3-yl]carbamimidoyl]phenoxy]ethoxyimino]acetyl]amino]-2,2-dimethyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(\C=1N=C(N)SC=1)=N/OCCOC1=CC=C(C(N)=N[C@@H]2CNCC2)C=C1 IXUCHBUKQYYVCQ-JUMRHNHYSA-N 0.000 description 1
• CDGJTKZKKHLQQN-GSVOUGTGSA-N [(3s)-3-amino-2,2-dimethyl-4-oxoazetidin-1-yl] hydrogen sulfate Chemical compound CC1(C)[C@H](N)C(=O)N1OS(O)(=O)=O CDGJTKZKKHLQQN-GSVOUGTGSA-N 0.000 description 1
• JMKMQEBMGISCRD-SCSAIBSYSA-N [(3s)-3-amino-2,2-dimethyl-4-oxoazetidin-1-yl]oxymethanesulfonic acid Chemical compound CC1(C)[C@H](N)C(=O)N1OCS(O)(=O)=O JMKMQEBMGISCRD-SCSAIBSYSA-N 0.000 description 1
• BMCHDXQXEWMXQQ-UHFFFAOYSA-N [3-[tert-butyl(dimethyl)silyl]oxy-2-[4-[N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenoxy]propyl] acetate Chemical compound CC(=O)OCC(CO[Si](C)(C)C(C)(C)C)Oc1ccc(cc1)C(=N)NC(=O)OC(C)(C)C BMCHDXQXEWMXQQ-UHFFFAOYSA-N 0.000 description 1
• NDEJTWZEHBOMLA-UHFFFAOYSA-N [3-[tert-butyl(dimethyl)silyl]oxy-2-hydroxypropyl] acetate Chemical compound CC(=O)OCC(O)CO[Si](C)(C)C(C)(C)C NDEJTWZEHBOMLA-UHFFFAOYSA-N 0.000 description 1
• YPLLGNQGNYMWBK-UHFFFAOYSA-N [3-hydroxy-2-[4-[N'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenoxy]propyl] acetate Chemical compound CC(=O)OCC(CO)Oc1ccc(cc1)C(=N)NC(=O)OC(C)(C)C YPLLGNQGNYMWBK-UHFFFAOYSA-N 0.000 description 1
• MNDOZACGIKCAKR-UHFFFAOYSA-N [4-[tert-butyl(dimethyl)silyl]oxy-3-hydroxybutyl] acetate Chemical compound CC(=O)OCCC(O)CO[Si](C)(C)C(C)(C)C MNDOZACGIKCAKR-UHFFFAOYSA-N 0.000 description 1
• 210000000683 abdominal cavity Anatomy 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical compound CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 description 1
• 229960001171 acetohydroxamic acid Drugs 0.000 description 1
• 230000003213 activating effect Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 230000009798 acute exacerbation Effects 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 description 1
• 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
• 230000001668 ameliorated effect Effects 0.000 description 1
• 229950003476 aminothiazole Drugs 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 201000004612 anterior uveitis Diseases 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 238000009635 antibiotic susceptibility testing Methods 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 210000000436 anus Anatomy 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• NDCUAPJVLWFHHB-UHNVWZDZSA-N avibactam Chemical compound C1N2[C@H](C(N)=O)CC[C@@]1([H])N(OS(O)(=O)=O)C2=O NDCUAPJVLWFHHB-UHNVWZDZSA-N 0.000 description 1
• 229960002379 avibactam Drugs 0.000 description 1
• 244000052616 bacterial pathogen Species 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• FJQGKEXJRAUURU-UHFFFAOYSA-N benzhydryl 2-aminooxy-3-[3-hydroxy-4-[(Z)-N'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenoxy]propanoate Chemical compound CC(C)(C)OC(=O)NC(=N)c1ccc(OCC(ON)C(=O)OC(c2ccccc2)c2ccccc2)cc1O FJQGKEXJRAUURU-UHFFFAOYSA-N 0.000 description 1
• VIGVFHPLHHHYPW-UHFFFAOYSA-N benzhydryl 2-aminooxy-3-[4-[n-[(2-methylpropan-2-yl)oxycarbonyl]-n-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]carbamimidoyl]phenoxy]propanoate Chemical compound C1=CC(C(=N)N(C(=O)OC(C)(C)C)CCNC(=O)OC(C)(C)C)=CC=C1OCC(ON)C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 VIGVFHPLHHHYPW-UHFFFAOYSA-N 0.000 description 1
• HHUXSGGXUNYOEQ-UHFFFAOYSA-N benzhydryl 2-hydroxy-3-[4-[(z)-n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenoxy]propanoate Chemical compound C1=CC(C(/N)=N/C(=O)OC(C)(C)C)=CC=C1OCC(O)C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 HHUXSGGXUNYOEQ-UHFFFAOYSA-N 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 229940073608 benzyl chloride Drugs 0.000 description 1
• 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 239000008280 blood Substances 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000006161 blood agar Substances 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 206010006451 bronchitis Diseases 0.000 description 1
• 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 108010068385 carbapenemase Proteins 0.000 description 1
• 229940041011 carbapenems Drugs 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
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 150000001768 cations Chemical class 0.000 description 1
• 230000004700 cellular uptake Effects 0.000 description 1
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
• JWMLCCRPDOIBAV-UHFFFAOYSA-N chloro(methylsulfanyl)methane Chemical compound CSCCl JWMLCCRPDOIBAV-UHFFFAOYSA-N 0.000 description 1
• 208000003167 cholangitis Diseases 0.000 description 1
• 201000001352 cholecystitis Diseases 0.000 description 1
• 208000007451 chronic bronchitis Diseases 0.000 description 1
• HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
• 229960003324 clavulanic acid Drugs 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
• 201000007717 corneal ulcer Diseases 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 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 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 201000003146 cystitis Diseases 0.000 description 1
• 238000007872 degassing Methods 0.000 description 1
• 238000006392 deoxygenation reaction Methods 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
• 229940117389 dichlorobenzene Drugs 0.000 description 1
• MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical compound ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical class CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• 206010062952 diffuse panbronchiolitis Diseases 0.000 description 1
• 229940043279 diisopropylamine Drugs 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• YVBIIQSBXHFITH-UHFFFAOYSA-N ditert-butyl 4-aminopyrazolidine-1,2-dicarboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N)CN1C(=O)OC(C)(C)C YVBIIQSBXHFITH-UHFFFAOYSA-N 0.000 description 1
• BLMWSPAWQMUBGA-UHFFFAOYSA-N ditert-butyl 4-azidopyrazolidine-1,2-dicarboxylate Chemical compound CC(C)(C)OC(=O)N1CC(N=[N+]=[N-])CN1C(=O)OC(C)(C)C BLMWSPAWQMUBGA-UHFFFAOYSA-N 0.000 description 1
• ANDOBGGLHFHRJH-UHFFFAOYSA-N ditert-butyl 4-hydroxypyrazolidine-1,2-dicarboxylate Chemical compound CC(C)(C)OC(=O)N1CC(O)CN1C(=O)OC(C)(C)C ANDOBGGLHFHRJH-UHFFFAOYSA-N 0.000 description 1
• ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 1
• 239000003651 drinking water Substances 0.000 description 1
• 235000020188 drinking water Nutrition 0.000 description 1
• 230000009977 dual effect Effects 0.000 description 1
• 210000005069 ears Anatomy 0.000 description 1
• 230000002500 effect on skin Effects 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 206010014665 endocarditis Diseases 0.000 description 1
• 210000000918 epididymis Anatomy 0.000 description 1
• 201000010063 epididymitis Diseases 0.000 description 1
• 150000002148 esters Chemical group 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• UNZUMKCIIIFEJI-UHFFFAOYSA-N ethyl 2-(1,3-dioxoisoindol-2-yl)oxy-2-methylpropanoate Chemical compound C1=CC=C2C(=O)N(OC(C)(C)C(=O)OCC)C(=O)C2=C1 UNZUMKCIIIFEJI-UHFFFAOYSA-N 0.000 description 1
• CXAFOUVBWLSQHX-UHFFFAOYSA-N ethyl 2-(4-cyanophenoxy)-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(C#N)C=C1 CXAFOUVBWLSQHX-UHFFFAOYSA-N 0.000 description 1
• SGOIJJCYRJIICZ-UHFFFAOYSA-N ethyl 2-[2-(oxan-2-yloxy)ethoxy]-1,3-thiazole-4-carboxylate Chemical compound CCOC(=O)C1=CSC(OCCOC2OCCCC2)=N1 SGOIJJCYRJIICZ-UHFFFAOYSA-N 0.000 description 1
• QRDQCWFFJNRRDE-UHFFFAOYSA-N ethyl 2-aminooxy-2-methylpropanoate Chemical compound CCOC(=O)C(C)(C)ON QRDQCWFFJNRRDE-UHFFFAOYSA-N 0.000 description 1
• XZTDSBXASFJQMI-UHFFFAOYSA-N ethyl 2-hydroxy-3-[6-[n'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]pyridin-3-yl]oxypropanoate Chemical compound CCOC(=O)C(O)COC1=CC=C(C(N)=NC(=O)OC(C)(C)C)N=C1 XZTDSBXASFJQMI-UHFFFAOYSA-N 0.000 description 1
• HSQYNCTUQIVXJD-UHFFFAOYSA-N ethyl 2-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]oxypropanoate Chemical compound CCOC(=O)C(C)(C)ONC(=O)OC(C)(C)C HSQYNCTUQIVXJD-UHFFFAOYSA-N 0.000 description 1
• OMGLOQRFAJAMTB-UHFFFAOYSA-N ethyl 2-methyl-3-oxo-1h-pyrazole-5-carboxylate Chemical compound CCOC(=O)C1=CC(=O)N(C)N1 OMGLOQRFAJAMTB-UHFFFAOYSA-N 0.000 description 1
• VNUSINVYWIWHPG-UHFFFAOYSA-N ethyl 2-methyl-5-[2-(oxan-2-yloxy)ethoxy]pyrazole-3-carboxylate Chemical compound CN1C(C(=O)OCC)=CC(OCCOC2OCCCC2)=N1 VNUSINVYWIWHPG-UHFFFAOYSA-N 0.000 description 1
• BLFWSORQDIUISI-UHFFFAOYSA-N ethyl 3-bromo-1,2-oxazole-5-carboxylate Chemical compound CCOC(=O)C1=CC(Br)=NO1 BLFWSORQDIUISI-UHFFFAOYSA-N 0.000 description 1
• YVKRWIVXIPGKTL-UHFFFAOYSA-N ethyl 5-amino-1,3,4-thiadiazole-2-carboxylate Chemical compound CCOC(=O)C1=NN=C(N)S1 YVKRWIVXIPGKTL-UHFFFAOYSA-N 0.000 description 1
• KDZLTNORBKZJKE-UHFFFAOYSA-N ethyl 5-bromo-1,3,4-thiadiazole-2-carboxylate Chemical compound CCOC(=O)C1=NN=C(Br)S1 KDZLTNORBKZJKE-UHFFFAOYSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 1
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
• 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 1
• 208000011323 eye infectious disease Diseases 0.000 description 1
• 239000012065 filter cake Substances 0.000 description 1
• 238000000806 fluorine-19 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 238000005755 formation reaction Methods 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
• 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
• 230000022244 formylation Effects 0.000 description 1
• 238000006170 formylation reaction Methods 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 235000013905 glycine and its sodium salt Nutrition 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 229940037467 helicobacter pylori Drugs 0.000 description 1
• 239000004312 hexamethylene tetramine Substances 0.000 description 1
• 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
• 150000004677 hydrates Chemical class 0.000 description 1
• 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• KJDJPXUIZYHXEZ-UHFFFAOYSA-N hydrogen sulfate;methylaminoazanium Chemical compound CN[NH3+].OS([O-])(=O)=O KJDJPXUIZYHXEZ-UHFFFAOYSA-N 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 229960002182 imipenem Drugs 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 201000007119 infective endocarditis Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000011081 inoculation Methods 0.000 description 1
• 239000001023 inorganic pigment Substances 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 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
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 229960002725 isoflurane Drugs 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 150000004715 keto acids Chemical class 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 229940115932 legionella pneumophila Drugs 0.000 description 1
• 231100000225 lethality Toxicity 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000006193 liquid solution Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• MHCFAGZWMAWTNR-UHFFFAOYSA-M lithium perchlorate Chemical compound [Li+].[O-]Cl(=O)(=O)=O MHCFAGZWMAWTNR-UHFFFAOYSA-M 0.000 description 1
• 229910001486 lithium perchlorate Inorganic materials 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 231100000053 low toxicity Toxicity 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 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
• 238000004949 mass spectrometry Methods 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 208000004396 mastitis Diseases 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• JBWMSSZODZMFQS-HNCPQSOCSA-N methyl (2R)-2-hydroxy-3-[4-(C-methoxycarbonimidoyl)phenoxy]propanoate hydrochloride Chemical compound Cl.COC([C@@H](COC1=CC=C(C=C1)C(=N)OC)O)=O JBWMSSZODZMFQS-HNCPQSOCSA-N 0.000 description 1
• OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
• BFDKJGIFIYOVBP-UHFFFAOYSA-N methyl 2-hydroxy-3-[4-[n'-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]carbamimidoyl]phenoxy]propanoate Chemical compound COC(=O)C(O)COC1=CC=C(C(N)=NCCNC(=O)OC(C)(C)C)C=C1 BFDKJGIFIYOVBP-UHFFFAOYSA-N 0.000 description 1
• OQPMVQFDAXAOPR-UHFFFAOYSA-N methyl 2-hydroxy-3-[4-[n-[(2-methylpropan-2-yl)oxycarbonyl]-n-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]carbamimidoyl]phenoxy]propanoate Chemical compound COC(=O)C(O)COC1=CC=C(C(=N)N(CCNC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)C=C1 OQPMVQFDAXAOPR-UHFFFAOYSA-N 0.000 description 1
• LPEKGGXMPWTOCB-UHFFFAOYSA-N methyl 2-hydroxypropionate Chemical compound COC(=O)C(C)O LPEKGGXMPWTOCB-UHFFFAOYSA-N 0.000 description 1
• IYAQFZAPKKWPNU-UHFFFAOYSA-N methyl 2-methyl-5-oxo-1h-pyrazole-3-carboxylate Chemical compound COC(=O)C1=CC(=O)NN1C IYAQFZAPKKWPNU-UHFFFAOYSA-N 0.000 description 1
• NRBCTPRIYOSCDD-UHFFFAOYSA-N methyl 4-(2,3-dihydroxypropoxy)benzenecarboximidate hydrochloride Chemical compound Cl.COC(C1=CC=C(C=C1)OCC(CO)O)=N NRBCTPRIYOSCDD-UHFFFAOYSA-N 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
• 230000000813 microbial effect Effects 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000013336 milk Nutrition 0.000 description 1
• 239000008267 milk Substances 0.000 description 1
• 210000004080 milk Anatomy 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 229940041009 monobactams Drugs 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• 229940076266 morganella morganii Drugs 0.000 description 1
• 239000012452 mother liquor Substances 0.000 description 1
• 230000036457 multidrug resistance Effects 0.000 description 1
• DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
• APTNXGQTESXKBG-UHFFFAOYSA-N n,n-diethylethanamine;n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(CC)CC.CCN(C(C)C)C(C)C APTNXGQTESXKBG-UHFFFAOYSA-N 0.000 description 1
• OWIUPIRUAQMTTK-UHFFFAOYSA-M n-aminocarbamate Chemical compound NNC([O-])=O OWIUPIRUAQMTTK-UHFFFAOYSA-M 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 229920005615 natural polymer Polymers 0.000 description 1
• 208000004995 necrotizing enterocolitis Diseases 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
• HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
• IOQPZZOEVPZRBK-UHFFFAOYSA-N octan-1-amine Chemical class CCCCCCCCN IOQPZZOEVPZRBK-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 150000002924 oxiranes Chemical group 0.000 description 1
• LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
• 201000006195 perinatal necrotizing enterocolitis Diseases 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 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
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 229910000160 potassium phosphate Inorganic materials 0.000 description 1
• 235000011009 potassium phosphates Nutrition 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 244000144977 poultry Species 0.000 description 1
• 235000013594 poultry meat Nutrition 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
• 229960004919 procaine Drugs 0.000 description 1
• NWCBOWOTHFLANG-UHFFFAOYSA-N propan-2-yl methanimidate;hydrochloride Chemical compound Cl.CC(C)OC=N NWCBOWOTHFLANG-UHFFFAOYSA-N 0.000 description 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 201000007094 prostatitis Diseases 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
• KQTCXMALIPUBAX-UHFFFAOYSA-N pyrazolidine-1,2-dicarboxylic acid Chemical compound OC(=O)N1CCCN1C(O)=O KQTCXMALIPUBAX-UHFFFAOYSA-N 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• KNXKVYCVGXFLES-UHFFFAOYSA-N pyridine-2-carboximidamide Chemical compound NC(=N)C1=CC=CC=N1 KNXKVYCVGXFLES-UHFFFAOYSA-N 0.000 description 1
• FVGUUJNEJJPLCS-UHFFFAOYSA-N pyridine-3-carboximidamide Chemical compound NC(=N)C1=CC=CN=C1 FVGUUJNEJJPLCS-UHFFFAOYSA-N 0.000 description 1
• ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
• 229940070891 pyridium Drugs 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 238000007142 ring opening reaction Methods 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• 201000001223 septic arthritis Diseases 0.000 description 1
• XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
• 206010040872 skin infection Diseases 0.000 description 1
• 239000000779 smoke Substances 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 229910000342 sodium bisulfate Inorganic materials 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
• HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical class [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
• HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
• SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
• 239000012064 sodium phosphate buffer Substances 0.000 description 1
• RNVYQYLELCKWAN-UHFFFAOYSA-N solketal Chemical compound CC1(C)OCC(CO)O1 RNVYQYLELCKWAN-UHFFFAOYSA-N 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 description 1
• 229960005256 sulbactam Drugs 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 229920001059 synthetic polymer Polymers 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 235000019640 taste Nutrition 0.000 description 1
• LPQZKKCYTLCDGQ-WEDXCCLWSA-N tazobactam Chemical compound C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1 LPQZKKCYTLCDGQ-WEDXCCLWSA-N 0.000 description 1
• 229960003865 tazobactam Drugs 0.000 description 1
• CMIBWIAICVBURI-ZETCQYMHSA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1 CMIBWIAICVBURI-ZETCQYMHSA-N 0.000 description 1
• MQEQBDMKSURJRN-UHFFFAOYSA-N tert-butyl (NZ)-N-[amino-(3,5-dihydroxypyridin-2-yl)methylidene]carbamate Chemical compound C(C)(C)(C)OC(NC(=N)C1=NC=C(C=C1O)O)=O MQEQBDMKSURJRN-UHFFFAOYSA-N 0.000 description 1
• CZMVPLHWBSAAHG-UHFFFAOYSA-N tert-butyl (ne)-n-[amino-[5-(2-aminooxyethoxy)-1-methylpyrazol-3-yl]methylidene]carbamate Chemical compound CN1N=C(C(\N)=N/C(=O)OC(C)(C)C)C=C1OCCON CZMVPLHWBSAAHG-UHFFFAOYSA-N 0.000 description 1
• XJEFKVSBBZRTAH-UHFFFAOYSA-N tert-butyl (ne)-n-[amino-[5-(2-aminooxyethoxy)-2-methylpyrazol-3-yl]methylidene]carbamate Chemical compound CN1N=C(OCCON)C=C1\C(N)=N/C(=O)OC(C)(C)C XJEFKVSBBZRTAH-UHFFFAOYSA-N 0.000 description 1
• YHBFBZJNPHRUDP-UHFFFAOYSA-N tert-butyl (ne)-n-[amino-[6-(2-hydroxyethoxy)pyridazin-3-yl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)\N=C(\N)C1=CC=C(OCCO)N=N1 YHBFBZJNPHRUDP-UHFFFAOYSA-N 0.000 description 1
• HYMKCVMRDURCRL-UHFFFAOYSA-N tert-butyl (nz)-n-[amino-[2-(2-hydroxyethoxy)-1,3-thiazol-4-yl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)\N=C(/N)C1=CSC(OCCO)=N1 HYMKCVMRDURCRL-UHFFFAOYSA-N 0.000 description 1
• GDVIPSNEOZDMKO-UHFFFAOYSA-N tert-butyl (nz)-n-[amino-[4-(1-aminooxy-3-hydroxypropan-2-yl)oxyphenyl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)\N=C(/N)C1=CC=C(OC(CO)CON)C=C1 GDVIPSNEOZDMKO-UHFFFAOYSA-N 0.000 description 1
• AUAYXWGLPRIZFN-UHFFFAOYSA-N tert-butyl (nz)-n-[amino-[4-(2-hydroxyethoxy)pyridin-2-yl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)\N=C(/N)C1=CC(OCCO)=CC=N1 AUAYXWGLPRIZFN-UHFFFAOYSA-N 0.000 description 1
• ZVIDQKYSZOVBHM-UHFFFAOYSA-N tert-butyl 2-(4-hydroxyphenyl)-5-[(2-methylpropan-2-yl)oxycarbonylamino]-5,6-dihydro-4H-pyrimidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)NC1CN=C(N(C1)C(=O)OC(C)(C)C)c1ccc(O)cc1 ZVIDQKYSZOVBHM-UHFFFAOYSA-N 0.000 description 1
• ULKYSINGQAAZBF-UHFFFAOYSA-N tert-butyl 2-[4-(2-aminooxyethoxy)phenyl]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-5,6-dihydro-4h-pyrimidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC(NC(=O)OC(C)(C)C)CN=C1C1=CC=C(OCCON)C=C1 ULKYSINGQAAZBF-UHFFFAOYSA-N 0.000 description 1
• FYSPMCDWDNSQEZ-UHFFFAOYSA-N tert-butyl 4-[(2-methylpropan-2-yl)oxycarbonyl-[4-[(2-methylpropan-2-yl)oxycarbonyloxy]benzenecarboximidoyl]amino]piperidine-1-carboxylate Chemical compound C1=CC(OC(=O)OC(C)(C)C)=CC=C1C(=N)N(C(=O)OC(C)(C)C)C1CCN(C(=O)OC(C)(C)C)CC1 FYSPMCDWDNSQEZ-UHFFFAOYSA-N 0.000 description 1
• PSJQQTSUTZXYNK-UHFFFAOYSA-N tert-butyl 4-[(4-hydroxybenzenecarboximidoyl)-[(2-methylpropan-2-yl)oxycarbonyl]amino]piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N(C1CCN(CC1)C(=O)OC(C)(C)C)C(=N)c1ccc(O)cc1 PSJQQTSUTZXYNK-UHFFFAOYSA-N 0.000 description 1
• VMIPHHJKJFXIET-UHFFFAOYSA-N tert-butyl 5-[(2-methylpropan-2-yl)oxycarbonylamino]-2-(4-phenylmethoxyphenyl)-5,6-dihydro-4H-pyrimidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)NC1CN=C(N(C1)C(=O)OC(C)(C)C)c1ccc(OCc2ccccc2)cc1 VMIPHHJKJFXIET-UHFFFAOYSA-N 0.000 description 1
• LDANTHMJWCBLHM-UHFFFAOYSA-N tert-butyl N-[4-(2,3-dihydroxypropoxy)benzenecarboximidoyl]carbamate Chemical compound C(C)(C)(C)OC(NC(=N)C1=CC=C(C=C1)OCC(CO)O)=O LDANTHMJWCBLHM-UHFFFAOYSA-N 0.000 description 1
• DBZMCZNDOYDYOT-UHFFFAOYSA-N tert-butyl N-[N'-[4-(2-aminooxypropoxy)phenyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate Chemical compound CC(COc1ccc(NC(NC(=O)OC(C)(C)C)=NC(=O)OC(C)(C)C)cc1)ON DBZMCZNDOYDYOT-UHFFFAOYSA-N 0.000 description 1
• MJAROACJDDOXFG-UHFFFAOYSA-N tert-butyl N-[amino-[4-(2-aminooxy-4-hydroxybutoxy)phenyl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)NC(=N)c1ccc(OCC(CCO)ON)cc1 MJAROACJDDOXFG-UHFFFAOYSA-N 0.000 description 1
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 1
• AUYMZOKWXOTXHN-UHFFFAOYSA-N tert-butyl n,n-diethylcarbamate Chemical compound CCN(CC)C(=O)OC(C)(C)C AUYMZOKWXOTXHN-UHFFFAOYSA-N 0.000 description 1
• FFCXTFAZMDAIIX-UHFFFAOYSA-N tert-butyl n-(1,3-diaminopropan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(CN)CN FFCXTFAZMDAIIX-UHFFFAOYSA-N 0.000 description 1
• ZOGLEOIAQNHQHA-UHFFFAOYSA-N tert-butyl n-(1-hydroxy-2-methylpropan-2-yl)oxycarbamate Chemical compound CC(C)(C)OC(=O)NOC(C)(C)CO ZOGLEOIAQNHQHA-UHFFFAOYSA-N 0.000 description 1
• UYNSYFDLTSSUNI-UHFFFAOYSA-N tert-butyl n-(2-aminopropyl)carbamate Chemical compound CC(N)CNC(=O)OC(C)(C)C UYNSYFDLTSSUNI-UHFFFAOYSA-N 0.000 description 1
• WEDUCEYDCOUVRM-UHFFFAOYSA-N tert-butyl n-(2-pyrrolidin-1-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN1CCCC1 WEDUCEYDCOUVRM-UHFFFAOYSA-N 0.000 description 1
• YRQMBQUMJFVZLF-UHFFFAOYSA-N tert-butyl n-(4-hydroxyphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(O)C=C1 YRQMBQUMJFVZLF-UHFFFAOYSA-N 0.000 description 1
• TYSZETYVESRFNT-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylamino]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)OC(C)(C)C TYSZETYVESRFNT-UHFFFAOYSA-N 0.000 description 1
• LQLVMJLTSCMVMK-UHFFFAOYSA-N tert-butyl n-[2-(1-methylpyrrolidin-1-ium-1-yl)ethyl]carbamate;iodide Chemical compound [I-].CC(C)(C)OC(=O)NCC[N+]1(C)CCCC1 LQLVMJLTSCMVMK-UHFFFAOYSA-N 0.000 description 1
• CPCMDILPLNDKSF-UHFFFAOYSA-N tert-butyl n-[2-[[amino-[4-(2-aminooxyethoxy)phenyl]methylidene]amino]-3-hydroxypropyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC(CO)N=C(N)C1=CC=C(OCCON)C=C1 CPCMDILPLNDKSF-UHFFFAOYSA-N 0.000 description 1
• AJTKQGMYQBMZGS-UHFFFAOYSA-N tert-butyl n-[2-[[amino-[4-(2-aminooxyethoxy)phenyl]methylidene]amino]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCN=C(N)C1=CC=C(OCCON)C=C1 AJTKQGMYQBMZGS-UHFFFAOYSA-N 0.000 description 1
• QYVFEFFJTQKDTK-UHFFFAOYSA-N tert-butyl n-[2-amino-3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC(N)CNC(=O)OC(C)(C)C QYVFEFFJTQKDTK-UHFFFAOYSA-N 0.000 description 1
• WBFZSVLIQOAVEV-UHFFFAOYSA-N tert-butyl n-[4-(2-bromoethoxy)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(OCCBr)C=C1 WBFZSVLIQOAVEV-UHFFFAOYSA-N 0.000 description 1
• NQWHESDNWKTUAS-UHFFFAOYSA-N tert-butyl n-[4-[2-(1,3-dioxoisoindol-2-yl)oxyethoxy]phenyl]carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1OCCON1C(=O)C2=CC=CC=C2C1=O NQWHESDNWKTUAS-UHFFFAOYSA-N 0.000 description 1
• QFNFDHNZVTWZED-UHFFFAOYSA-N tert-butyl n-[[(2-methylpropan-2-yl)oxycarbonylamino]-pyrazol-1-ylmethylidene]carbamate Chemical compound CC(C)(C)OC(=O)NC(=NC(=O)OC(C)(C)C)N1C=CC=N1 QFNFDHNZVTWZED-UHFFFAOYSA-N 0.000 description 1
• MMNOUZDSXCJWAT-UHFFFAOYSA-N tert-butyl n-[amino-[4-[2-aminooxy-3-[tert-butyl(dimethyl)silyl]oxypropoxy]phenyl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)N=C(N)C1=CC=C(OCC(CO[Si](C)(C)C(C)(C)C)ON)C=C1 MMNOUZDSXCJWAT-UHFFFAOYSA-N 0.000 description 1
• APXHGLJFIFBIOB-UHFFFAOYSA-N tert-butyl n-[amino-[5-(2-aminooxyethoxy)-1,3,4-thiadiazol-2-yl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)N=C(N)C1=NN=C(OCCON)S1 APXHGLJFIFBIOB-UHFFFAOYSA-N 0.000 description 1
• ISCRIXFCQVUDPT-UHFFFAOYSA-N tert-butyl n-[amino-[5-(2-hydroxyethoxy)-1,3,4-thiadiazol-2-yl]methylidene]carbamate Chemical compound CC(C)(C)OC(=O)N=C(N)C1=NN=C(OCCO)S1 ISCRIXFCQVUDPT-UHFFFAOYSA-N 0.000 description 1
• ZJQJJPACPLHZFT-UHFFFAOYSA-N tert-butyl-(1,3-dibromopropan-2-yloxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC(CBr)CBr ZJQJJPACPLHZFT-UHFFFAOYSA-N 0.000 description 1
• TWRVYXVQOJCHIF-UHFFFAOYSA-N tert-butyl-chloro-methylsilane Chemical compound C[SiH](Cl)C(C)(C)C TWRVYXVQOJCHIF-UHFFFAOYSA-N 0.000 description 1
• 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 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-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
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
• 229940041007 third-generation cephalosporins Drugs 0.000 description 1
• 229960002898 threonine Drugs 0.000 description 1
• VAMSVIZLXJOLHZ-QWFSEIHXSA-N tigemonam Chemical compound O=C1N(OS(O)(=O)=O)C(C)(C)[C@@H]1NC(=O)C(=N/OCC(O)=O)\C1=CSC(N)=N1 VAMSVIZLXJOLHZ-QWFSEIHXSA-N 0.000 description 1
• 229950010206 tigemonam Drugs 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• 206010044008 tonsillitis Diseases 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
• 238000010267 two-fold dilution method Methods 0.000 description 1
• 201000008297 typhoid fever Diseases 0.000 description 1
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
• 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
• 210000003708 urethra Anatomy 0.000 description 1
• 208000000143 urethritis Diseases 0.000 description 1
• 210000001635 urinary tract Anatomy 0.000 description 1
• 238000005292 vacuum distillation Methods 0.000 description 1
• 239000000052 vinegar Substances 0.000 description 1
• 235000021419 vinegar Nutrition 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
• 239000002132 β-lactam antibiotic Substances 0.000 description 1
• 229940124586 β-lactam antibiotics Drugs 0.000 description 1