JP4602759B2 - β−ラクタマーゼ阻害剤としての二環式６−アルキリデン−ペネム - Google Patents

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Publication number

JP4602759B2

JP4602759B2 JP2004501418A JP2004501418A JP4602759B2 JP 4602759 B2 JP4602759 B2 JP 4602759B2 JP 2004501418 A JP2004501418 A JP 2004501418A JP 2004501418 A JP2004501418 A JP 2004501418A JP 4602759 B2 JP4602759 B2 JP 4602759B2

Authority

JP

Japan

Prior art keywords

oxo

thia

carboxylic acid

ene

ylmethylene

Prior art date

2002-05-01

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

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• 125000002619 bicyclic group Chemical group 0.000 title description 14
• 239000003781 beta lactamase inhibitor Substances 0.000 title description 5
• 229940126813 beta-lactamase inhibitor Drugs 0.000 title description 5
• 239000000203 mixture Substances 0.000 claims description 227
• -1 5,6,7,8-tetrahydroimidazo [1,2-a] pyrazin-2-ylmethylene Chemical group 0.000 claims description 176
• 150000001875 compounds Chemical class 0.000 claims description 163
• 230000002829 reductive effect Effects 0.000 claims description 139
• 229910052760 oxygen Inorganic materials 0.000 claims description 117
• 229910052799 carbon Inorganic materials 0.000 claims description 112
• 229910052717 sulfur Inorganic materials 0.000 claims description 89
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 85
• 238000002360 preparation method Methods 0.000 claims description 67
• 229910052757 nitrogen Inorganic materials 0.000 claims description 59
• 125000003118 aryl group Chemical group 0.000 claims description 38
• 125000001072 heteroaryl group Chemical group 0.000 claims description 38
• 238000000034 method Methods 0.000 claims description 29
• 229910052739 hydrogen Inorganic materials 0.000 claims description 24
• 239000003782 beta lactam antibiotic agent Substances 0.000 claims description 23
• 239000002132 β-lactam antibiotic Substances 0.000 claims description 23
• 229940124586 β-lactam antibiotics Drugs 0.000 claims description 23
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 22
• 125000005842 heteroatom Chemical group 0.000 claims description 18
• 239000011734 sodium Substances 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 17
• ZIHYVLFLVDRNED-UHFFFAOYSA-M sodium;2-methylhept-2-enoate Chemical compound [Na+].CCCCC=C(C)C([O-])=O ZIHYVLFLVDRNED-UHFFFAOYSA-M 0.000 claims description 16
• FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 claims description 15
• 229910052708 sodium Inorganic materials 0.000 claims description 15
• 125000004122 cyclic group Chemical group 0.000 claims description 13
• 239000003242 anti bacterial agent Substances 0.000 claims description 11
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 10
• 229940088710 antibiotic agent Drugs 0.000 claims description 9
• 150000002148 esters Chemical class 0.000 claims description 9
• 125000006239 protecting group Chemical group 0.000 claims description 9
• 150000003839 salts Chemical class 0.000 claims description 9
• JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 8
• 229960002292 piperacillin Drugs 0.000 claims description 8
• WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 claims description 8
• 229910052727 yttrium Inorganic materials 0.000 claims description 8
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 229960003022 amoxicillin Drugs 0.000 claims description 6
• LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 6
• 159000000000 sodium salts Chemical class 0.000 claims description 6
• 229930186147 Cephalosporin Natural products 0.000 claims description 5
• 229930182555 Penicillin Natural products 0.000 claims description 5
• 125000003545 alkoxy group Chemical group 0.000 claims description 5
• 229940124587 cephalosporin Drugs 0.000 claims description 5
• 150000001780 cephalosporins Chemical class 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
• 208000035143 Bacterial infection Diseases 0.000 claims description 4
• 208000022362 bacterial infectious disease Diseases 0.000 claims description 4
• 230000015572 biosynthetic process Effects 0.000 claims description 4
• 229940049954 penicillin Drugs 0.000 claims description 4
• 229910052698 phosphorus Inorganic materials 0.000 claims description 4
• 230000008569 process Effects 0.000 claims description 4
• GVHDSAYSZMRHCR-WIMVAJRLSA-M sodium (6Z)-6-[(6,6-dimethyl-7,8-dihydro-5H-imidazo[1,2-a]pyridin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound CC1(CCC2=NC(=CN2C1)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-])C.[Na+] GVHDSAYSZMRHCR-WIMVAJRLSA-M 0.000 claims description 4
• MJECQFMGPFJWIJ-WENINEFDSA-M sodium;(6z)-6-[(7-methyl-6-oxo-5,8-dihydroimidazo[1,2-a]pyrazin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].C1C(=O)N(C)CC2=NC(\C=C/3C(N4C(=CSC4\3)C([O-])=O)=O)=CN21 MJECQFMGPFJWIJ-WENINEFDSA-M 0.000 claims description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 4
• QQDDJIUJAPMCCX-SIBGDRKGSA-N (5r,6z)-6-[(5-benzyl-6,7-dihydro-4h-thieno[3,2-c]pyridin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1([C@@H]2SC=C1C(=O)O)C(=O)\C2=C\C(SC=1CC2)=CC=1CN2CC1=CC=CC=C1 QQDDJIUJAPMCCX-SIBGDRKGSA-N 0.000 claims description 3
• 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
• YCUYDSZGQWAXRY-UHFFFAOYSA-N CC(=CCCCC)C(=O)O.[Na] Chemical compound CC(=CCCCC)C(=O)O.[Na] YCUYDSZGQWAXRY-UHFFFAOYSA-N 0.000 claims description 3
• JWCSIUVGFCSJCK-CAVRMKNVSA-N Disodium Moxalactam Chemical compound N([C@]1(OC)C(N2C(=C(CSC=3N(N=NN=3)C)CO[C@@H]21)C(O)=O)=O)C(=O)C(C(O)=O)C1=CC=C(O)C=C1 JWCSIUVGFCSJCK-CAVRMKNVSA-N 0.000 claims description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
• 229960000723 ampicillin Drugs 0.000 claims description 3
• AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 3
• 229960000433 latamoxef Drugs 0.000 claims description 3
• SUGVDSNWWQKWCE-LESAWYNJSA-M sodium (5R,6Z)-6-(4,6-dihydropyrazolo[1,5-c][1,3]thiazol-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound O=C1/C(/[C@H]2SC=C(N12)C(=O)[O-])=C/C1=NN2CSCC2=C1.[Na+] SUGVDSNWWQKWCE-LESAWYNJSA-M 0.000 claims description 3
• PXKLWHWKLDQKEF-DZIFNFPVSA-M sodium (5R,6Z)-6-(5,7-dihydroimidazo[1,2-c][1,3]thiazol-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1C2=NC(=CN2CS1)/C=C/3\[C@@H]4N(C3=O)C(=CS4)C(=O)[O-].[Na+] PXKLWHWKLDQKEF-DZIFNFPVSA-M 0.000 claims description 3
• HHGFWQVGBHTXHX-NGRDVXTNSA-M sodium (6Z)-6-(6,8-dihydro-5H-imidazo[2,1-c][1,4]thiazin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound N=1C(=CN2C=1CSCC2)\C=C\1/C2SC=C(N2C/1=O)C(=O)[O-].[Na+] HHGFWQVGBHTXHX-NGRDVXTNSA-M 0.000 claims description 3
• XREVOTNYKGMPMS-WONROIIJSA-M sodium (6Z)-6-[(7-methyl-6,8-dihydro-5H-imidazo[1,2-a]pyrazin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound CN1CCN2C=C(N=C2C1)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-].[Na+] XREVOTNYKGMPMS-WONROIIJSA-M 0.000 claims description 3
• RFSWVJXWZXQOSW-NGRDVXTNSA-M sodium;(6z)-6-(6,8-dihydro-5h-imidazo[2,1-c][1,4]oxazin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].C1COCC2=NC(/C=C3/C(=O)N4C3SC=C4C(=O)[O-])=CN21 RFSWVJXWZXQOSW-NGRDVXTNSA-M 0.000 claims description 3
• OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 claims description 3
• 229960004659 ticarcillin Drugs 0.000 claims description 3
• JETQIUPBHQNHNZ-NJBDSQKTSA-N (2s,5r,6r)-3,3-dimethyl-7-oxo-6-[[(2r)-2-phenyl-2-sulfoacetyl]amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound C1([C@H](C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)S(O)(=O)=O)=CC=CC=C1 JETQIUPBHQNHNZ-NJBDSQKTSA-N 0.000 claims description 2
• DWYDARUUOLMALM-TWLAMCEISA-N (5r,6z)-6-(6,7-dihydro-4h-pyrazolo[5,1-c][1,4]oxazin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1=C2COCCN2N=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O DWYDARUUOLMALM-TWLAMCEISA-N 0.000 claims description 2
• TZHYRIOYHMAWIJ-KGHNQEBZSA-N (5r,6z)-7-oxo-6-[(4-oxo-6,7-dihydropyrazolo[5,1-c][1,4]oxazin-2-yl)methylidene]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1=C2C(=O)OCCN2N=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)O TZHYRIOYHMAWIJ-KGHNQEBZSA-N 0.000 claims description 2
• NJRJPWDAUDRBDD-NVNXTCNLSA-N (6z)-6-[(7-benzyl-6,8-dihydro-5h-imidazo[1,2-a]pyrazin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CSC2N1C(=O)\C2=C\C(N=C1C2)=CN1CCN2CC1=CC=CC=C1 NJRJPWDAUDRBDD-NVNXTCNLSA-N 0.000 claims description 2
• VAEBCNPDQMGFNE-UHFFFAOYSA-N 6-(6,7-dihydro-4h-thieno[3,2-c]pyran-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1OCCC(S2)=C1C=C2C=C1C(=O)N2C1SC=C2C(=O)O VAEBCNPDQMGFNE-UHFFFAOYSA-N 0.000 claims description 2
• YKGCKZGARDHVBE-UHFFFAOYSA-N 6-(6,7-dihydro-4h-thieno[3,2-c]thiopyran-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1SCCC(S2)=C1C=C2C=C1C(=O)N2C1SC=C2C(=O)O YKGCKZGARDHVBE-UHFFFAOYSA-N 0.000 claims description 2
• GEBFRXZPTJKYPE-UHFFFAOYSA-N 6-[(5-ethoxycarbonyl-6,7-dihydro-4h-thieno[3,2-c]pyridin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1N(C(=O)OCC)CCC2=C1C=C(C=C1C(N3C(=CSC31)C(O)=O)=O)S2 GEBFRXZPTJKYPE-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims description 2
• FVUCWGGFZNLYLD-UHFFFAOYSA-M [Na+].C(C=CCCCC)C(=O)[O-] Chemical compound [Na+].C(C=CCCCC)C(=O)[O-] FVUCWGGFZNLYLD-UHFFFAOYSA-M 0.000 claims description 2
• WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound 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 claims description 2
• 229960003644 aztreonam Drugs 0.000 claims description 2
• CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 claims description 2
• 229960003866 cefaloridine Drugs 0.000 claims description 2
• 229960000603 cefalotin Drugs 0.000 claims description 2
• 229960001139 cefazolin Drugs 0.000 claims description 2
• MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 claims description 2
• 229960002588 cefradine Drugs 0.000 claims description 2
• 229940106164 cephalexin Drugs 0.000 claims description 2
• ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims description 2
• VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 claims description 2
• RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 claims description 2
• 125000002883 imidazolyl group Chemical group 0.000 claims description 2
• 235000019371 penicillin G benzathine Nutrition 0.000 claims description 2
• 229940056360 penicillin g Drugs 0.000 claims description 2
• OUQLXWMNFXEEGF-UYTGOYFPSA-M sodium (6Z)-6-(5,6-dihydro-4H-cyclopenta[b]furan-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1CC2=C(C1)OC(=C2)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-].[Na+] OUQLXWMNFXEEGF-UYTGOYFPSA-M 0.000 claims description 2
• 229960004932 sulbenicillin Drugs 0.000 claims description 2
• 125000004434 sulfur atom Chemical group 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• PHMQLKCJGJCTLT-VLQAWENLSA-M sodium (5R,6Z)-6-(2,3-dihydropyrazolo[5,1-b][1,3]thiazol-6-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound S1C=2N(CC1)N=C(C=2)\C=C\1/[C@H]2SC=C(N2C/1=O)C(=O)[O-].[Na+] PHMQLKCJGJCTLT-VLQAWENLSA-M 0.000 claims 1
• ZDKUWOPXFSFLND-WBFSQFMTSA-M sodium (5R,6Z)-6-(5,7-dihydro-4H-pyrazolo[1,5-c][1,3]thiazin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound N1=C(C=C2CCSCN12)\C=C\1/[C@H]2SC=C(N2C/1=O)C(=O)[O-].[Na+] ZDKUWOPXFSFLND-WBFSQFMTSA-M 0.000 claims 1
• VPGJCAZRMJTNIN-WONROIIJSA-M sodium (6Z)-6-[(5,5-dioxo-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]thiazin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1CS(=O)(=O)CC2=CC(=NN21)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-].[Na+] VPGJCAZRMJTNIN-WONROIIJSA-M 0.000 claims 1
• MAOMPSXLHMNKJY-VLQAWENLSA-M sodium;(5r,6z)-6-(2,3-dihydropyrazolo[5,1-b][1,3]oxazol-6-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].C1=C2OCCN2N=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)[O-] MAOMPSXLHMNKJY-VLQAWENLSA-M 0.000 claims 1
• VJIDJIHPACCJGS-CZLOGHIXSA-M sodium;(5r,6z)-6-[[5-[(4-methoxyphenyl)methyl]-6,7-dihydro-4h-thieno[3,2-c]pyridin-2-yl]methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].C1=CC(OC)=CC=C1CN1CC(C=C(\C=C/2C(N3C(=CS[C@@H]3\2)C([O-])=O)=O)S2)=C2CC1 VJIDJIHPACCJGS-CZLOGHIXSA-M 0.000 claims 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 374
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 300
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 246
• 239000000243 solution Substances 0.000 description 243
• 239000011541 reaction mixture Substances 0.000 description 207
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 130
• 239000007787 solid Substances 0.000 description 126
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 117
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 116
• 238000005481 NMR spectroscopy Methods 0.000 description 114
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 114
• 239000000706 filtrate Substances 0.000 description 112
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 111
• NPDLYUOYAGBHFB-WDSKDSINSA-N Asn-Arg Chemical compound NC(=O)C[C@H](N)C(=O)N[C@H](C(O)=O)CCCN=C(N)N NPDLYUOYAGBHFB-WDSKDSINSA-N 0.000 description 110
• 239000012044 organic layer Substances 0.000 description 103
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 100
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 99
• 238000006243 chemical reaction Methods 0.000 description 85
• 239000010410 layer Substances 0.000 description 85
• OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 83
• 239000012299 nitrogen atmosphere Substances 0.000 description 69
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• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 125000002009 alkene group Chemical group 0.000 description 2
• 125000005530 alkylenedioxy group Chemical group 0.000 description 2
• 238000004458 analytical method Methods 0.000 description 2
• 238000009635 antibiotic susceptibility testing Methods 0.000 description 2
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 2
• 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• 125000002393 azetidinyl group Chemical group 0.000 description 2
• 125000004069 aziridinyl group Chemical group 0.000 description 2
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 235000010290 biphenyl Nutrition 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 239000000872 buffer Substances 0.000 description 2
• 239000007853 buffer solution Substances 0.000 description 2
• 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 2
• 229960003324 clavulanic acid Drugs 0.000 description 2
• 239000012230 colorless oil Substances 0.000 description 2
• 150000003997 cyclic ketones Chemical class 0.000 description 2
• 239000002274 desiccant Substances 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 125000004663 dialkyl amino group Chemical group 0.000 description 2
• 125000005047 dihydroimidazolyl group Chemical group N1(CNC=C1)* 0.000 description 2
• 125000005048 dihydroisoxazolyl group Chemical group O1N(CC=C1)* 0.000 description 2
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
• MSPOSRHJXMILNK-UHFFFAOYSA-N ethyl 1h-pyrazole-5-carboxylate Chemical compound CCOC(=O)C1=CC=NN1 MSPOSRHJXMILNK-UHFFFAOYSA-N 0.000 description 2
• VICYTAYPKBLQFB-UHFFFAOYSA-N ethyl 3-bromo-2-oxopropanoate Chemical compound CCOC(=O)C(=O)CBr VICYTAYPKBLQFB-UHFFFAOYSA-N 0.000 description 2
• RLYRMESNENRMHE-UHFFFAOYSA-N ethyl 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-2-carboxylate Chemical compound C1CCCN2N=C(C(=O)OCC)C=C21 RLYRMESNENRMHE-UHFFFAOYSA-N 0.000 description 2
• LHPDOGQJGFQFFQ-UHFFFAOYSA-N ethyl 4,6-dihydropyrazolo[1,5-c][1,3]thiazole-2-carboxylate Chemical compound C1SCN2N=C(C(=O)OCC)C=C21 LHPDOGQJGFQFFQ-UHFFFAOYSA-N 0.000 description 2
• XJRGUTARDWMARO-UHFFFAOYSA-N ethyl 4,6-dihydropyrazolo[1,5-c][1,3]thiazole-3-carboxylate Chemical compound C1SCC2=C(C(=O)OCC)C=NN21 XJRGUTARDWMARO-UHFFFAOYSA-N 0.000 description 2
• OUXQIBFTSBUPKU-UHFFFAOYSA-N ethyl 5,5-dimethyl-4,6-dihydropyrrolo[1,2-b]pyrazole-2-carboxylate Chemical compound C1C(C)(C)CN2N=C(C(=O)OCC)C=C21 OUXQIBFTSBUPKU-UHFFFAOYSA-N 0.000 description 2
• KPERHFIXVOUTQW-UHFFFAOYSA-N ethyl 5,5-dimethyl-4,6-dihydropyrrolo[1,2-b]pyrazole-3-carboxylate Chemical compound C1C(C)(C)CC2=C(C(=O)OCC)C=NN21 KPERHFIXVOUTQW-UHFFFAOYSA-N 0.000 description 2
• MGGGSJRWNQFCLE-UHFFFAOYSA-N ethyl 5,6-dihydro-4h-pyrrolo[1,2-b]pyrazole-2-carboxylate Chemical compound C1CCN2N=C(C(=O)OCC)C=C21 MGGGSJRWNQFCLE-UHFFFAOYSA-N 0.000 description 2
• MTPPMSVRBRLEQF-UHFFFAOYSA-N ethyl 5,7-dihydro-4h-pyrazolo[1,5-c][1,3]thiazine-2-carboxylate Chemical compound C1CSCN2N=C(C(=O)OCC)C=C21 MTPPMSVRBRLEQF-UHFFFAOYSA-N 0.000 description 2
• TURPMJWIXJNODP-UHFFFAOYSA-N ethyl 5,7-dihydro-4h-pyrazolo[1,5-c][1,3]thiazine-3-carboxylate Chemical compound C1SCCC2=C(C(=O)OCC)C=NN21 TURPMJWIXJNODP-UHFFFAOYSA-N 0.000 description 2
• TTXMGIMDAFVKPD-UHFFFAOYSA-N ethyl 5-benzoyl-6,7-dihydro-4h-thieno[3,2-c]pyridine-2-carboxylate Chemical compound C1CC=2SC(C(=O)OCC)=CC=2CN1C(=O)C1=CC=CC=C1 TTXMGIMDAFVKPD-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• UAYKGOMDUQLCJS-UHFFFAOYSA-N ethylsulfanyl acetate Chemical compound CCSOC(C)=O UAYKGOMDUQLCJS-UHFFFAOYSA-N 0.000 description 2
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• 125000004634 hexahydroazepinyl group Chemical group N1(CCCCCC1)* 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 2
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 2
• 230000007246 mechanism Effects 0.000 description 2
• LTAFRIZVOKDEMU-UHFFFAOYSA-N morpholine-3-thione Chemical compound S=C1COCCN1 LTAFRIZVOKDEMU-UHFFFAOYSA-N 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 125000006574 non-aromatic ring group Chemical group 0.000 description 2
• 125000000962 organic group Chemical group 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 2
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• 244000052769 pathogen Species 0.000 description 2
• 239000008055 phosphate buffer solution Substances 0.000 description 2
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• 239000011574 phosphorus Substances 0.000 description 2
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• 125000003386 piperidinyl group Chemical group 0.000 description 2
• DXBWJLDFSICTIH-UHFFFAOYSA-N pyrazine-2-carbaldehyde Chemical compound O=CC1=CN=CC=N1 DXBWJLDFSICTIH-UHFFFAOYSA-N 0.000 description 2
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• 125000006413 ring segment Chemical group 0.000 description 2
• 238000013207 serial dilution Methods 0.000 description 2
• VYRUGALBOGAIQT-ZYFYRQFPSA-M sodium (6Z)-6-(6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1CC2=NC(=CN2C1)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-].[Na+] VYRUGALBOGAIQT-ZYFYRQFPSA-M 0.000 description 2
• 239000011780 sodium chloride Substances 0.000 description 2
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• MJECQFMGPFJWIJ-VOKCZWNHSA-M sodium;(6e)-6-[(7-methyl-6-oxo-5,8-dihydroimidazo[1,2-a]pyrazin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].C1C(=O)N(C)CC2=NC(\C=C\3C(N4C(=CSC4/3)C([O-])=O)=O)=CN21 MJECQFMGPFJWIJ-VOKCZWNHSA-M 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 210000002784 stomach Anatomy 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 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 2
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• 238000003786 synthesis reaction Methods 0.000 description 2
• 229960003865 tazobactam Drugs 0.000 description 2
• 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 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 2
• OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 2
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 2
• 231100000331 toxic Toxicity 0.000 description 2
• 230000002588 toxic effect Effects 0.000 description 2
• 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 2
• PSIXOASXDGVLRN-TWMPVWRBSA-N (4-nitrophenyl)methyl (5r)-6-[acetyloxy(2,3-dihydropyrazolo[5,1-b][1,3]thiazol-6-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)(Br)C(C2=NN3CCSC3=C2)OC(=O)C)C=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 PSIXOASXDGVLRN-TWMPVWRBSA-N 0.000 description 1
• LCTZQVNTKLMQSJ-NFOQDIRWSA-N (4-nitrophenyl)methyl (5r)-6-[acetyloxy(5,7-dihydro-4h-pyrazolo[1,5-c][1,3]thiazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)(Br)C(C2=NN3CSCCC3=C2)OC(=O)C)C=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 LCTZQVNTKLMQSJ-NFOQDIRWSA-N 0.000 description 1
• AGSPXMNLSOIYKW-NFOQDIRWSA-N (4-nitrophenyl)methyl (5r)-6-[acetyloxy(6,7-dihydro-4h-pyrazolo[5,1-c][1,4]oxazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)(Br)C(C2=NN3CCOCC3=C2)OC(=O)C)C=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 AGSPXMNLSOIYKW-NFOQDIRWSA-N 0.000 description 1
• FODPPWQYZITQNA-PDRFFQIWSA-N (4-nitrophenyl)methyl (5r)-6-[acetyloxy-(4-oxo-6,7-dihydropyrazolo[5,1-c][1,4]oxazin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)(Br)C(C2=NN3CCOC(=O)C3=C2)OC(=O)C)C=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 FODPPWQYZITQNA-PDRFFQIWSA-N 0.000 description 1
• IGPFZBQPJDMXJT-HWDGFJGFSA-N (4-nitrophenyl)methyl (5r)-6-[acetyloxy-(5,5-dimethyl-4,6-dihydropyrrolo[1,2-b]pyrazol-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)(Br)C(C2=NN3CC(C)(C)CC3=C2)OC(=O)C)C=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 IGPFZBQPJDMXJT-HWDGFJGFSA-N 0.000 description 1
• UZDLFQGOANLCIW-OTDMGWBDSA-N (4-nitrophenyl)methyl (5r)-6-[acetyloxy-[5-[(4-nitrophenyl)methoxycarbonyl]-6,7-dihydro-4h-pyrazolo[1,5-a]pyrazin-2-yl]methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound S([C@@H]12)C=C(C(=O)OCC=3C=CC(=CC=3)[N+]([O-])=O)N1C(=O)C2(Br)C(OC(=O)C)C(=NN1CC2)C=C1CN2C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 UZDLFQGOANLCIW-OTDMGWBDSA-N 0.000 description 1
• LQXPOUGMOWNAOI-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-formyl-6,7-dihydro-4h-pyrazolo[1,5-a]pyrazine-5-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)N1CC2=CC(C=O)=NN2CC1 LQXPOUGMOWNAOI-UHFFFAOYSA-N 0.000 description 1
• KQBDNQQUBREETF-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-methoxypiperazine-1-carboxylate Chemical compound COC1CNCCN1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 KQBDNQQUBREETF-UHFFFAOYSA-N 0.000 description 1
• ZWSZQIGAYDIYDM-UHFFFAOYSA-N (4-nitrophenyl)methyl 3-oxopiperazine-1-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)N1CC(=O)NCC1 ZWSZQIGAYDIYDM-UHFFFAOYSA-N 0.000 description 1
• NHKGBUFCOREANA-UHFFFAOYSA-N (4-nitrophenyl)methyl 6-amino-3,5-dihydro-2h-pyrazine-4-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)N1CC(=N)NCC1 NHKGBUFCOREANA-UHFFFAOYSA-N 0.000 description 1
• MHSGOABISYIYKP-UHFFFAOYSA-N (4-nitrophenyl)methyl carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(COC(Cl)=O)C=C1 MHSGOABISYIYKP-UHFFFAOYSA-N 0.000 description 1
• KJQIVTIQHAUTJV-UHFFFAOYSA-N (4-nitrophenyl)methyl pyrazine-2-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)C1=CN=CC=N1 KJQIVTIQHAUTJV-UHFFFAOYSA-N 0.000 description 1
• IMPOWBGVGHJTHS-UHFFFAOYSA-N (5,5-dimethyl-4,6-dihydropyrrolo[1,2-b]pyrazol-2-yl)methanol Chemical compound OCC1=NN2CC(C)(C)CC2=C1 IMPOWBGVGHJTHS-UHFFFAOYSA-N 0.000 description 1
• UMBIJIPNILTCBR-UHFFFAOYSA-N (5-benzyl-6,7-dihydro-4h-thieno[3,2-c]pyridin-2-yl)methanol Chemical compound C1CC=2SC(CO)=CC=2CN1CC1=CC=CC=C1 UMBIJIPNILTCBR-UHFFFAOYSA-N 0.000 description 1
• GHKOEXXIUYMVMX-UHFFFAOYSA-N (5-methyl-6,7-dihydro-4h-thieno[3,2-c]pyridin-2-yl)methanol Chemical compound C1N(C)CCC2=C1C=C(CO)S2 GHKOEXXIUYMVMX-UHFFFAOYSA-N 0.000 description 1
• BJDTWVQNEWIULP-RXMQYKEDSA-N (5R)-3-bromo-4-thia-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class BrC=1S[C@H]2N(C=1)C(C2)=O BJDTWVQNEWIULP-RXMQYKEDSA-N 0.000 description 1
• UCZMKFINTOCIJO-XGTXGMFGSA-N (5r)-6-[acetyloxy(6,8-dihydro-5h-imidazo[2,1-c][1,4]thiazin-3-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1SCCN2C(C(OC(=O)C)C3(Br)C(N4C(=CS[C@@H]43)C(O)=O)=O)=CN=C21 UCZMKFINTOCIJO-XGTXGMFGSA-N 0.000 description 1
• SDGCXMDTXHFBPH-SDMSXHDGSA-N (5r)-6-bromo-4-thia-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class S1C=CN2C(=O)C(Br)[C@H]21 SDGCXMDTXHFBPH-SDMSXHDGSA-N 0.000 description 1
• DFFVJNWUKHDODC-MEHWWPQUSA-N (5r,6z)-6-[(1-methyltriazol-4-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N1=NN(C)C=C1\C=C/1C(=O)N2C(C(O)=O)=CS[C@@H]2\1 DFFVJNWUKHDODC-MEHWWPQUSA-N 0.000 description 1
• GQXQTXHDCYOKOS-UJNBGNEJSA-N (5r,6z)-6-[(6-ethoxycarbonyl-5,7-dihydro-4h-furo[2,3-c]pyridin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1N(C(=O)OCC)CCC2=C1OC(\C=C/1C(N3C(=CS[C@@H]3\1)C(O)=O)=O)=C2 GQXQTXHDCYOKOS-UJNBGNEJSA-N 0.000 description 1
• IVFHCVAIVOSJKU-KRXBUXKQSA-N (6e)-6-[(7-methyl-6-oxo-5,8-dihydroimidazo[1,2-a]pyrazin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1C(=O)N(C)CC2=NC(\C=C\3C(N4C(=CSC4/3)C(O)=O)=O)=CN21 IVFHCVAIVOSJKU-KRXBUXKQSA-N 0.000 description 1
• IVFHCVAIVOSJKU-WAPJZHGLSA-N (6z)-6-[(7-methyl-6-oxo-5,8-dihydroimidazo[1,2-a]pyrazin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1C(=O)N(C)CC2=NC(\C=C/3C(N4C(=CSC4\3)C(O)=O)=O)=CN21 IVFHCVAIVOSJKU-WAPJZHGLSA-N 0.000 description 1
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 1
• 125000006828 (C2-C7) alkoxycarbonyl group Chemical group 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• JOKIQGQOKXGHDV-BYPYZUCNSA-N (R)-thiomorpholine-3-carboxylic acid Chemical compound OC(=O)[C@@H]1CSCCN1 JOKIQGQOKXGHDV-BYPYZUCNSA-N 0.000 description 1
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
• KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
• PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 1
• JVZZMANDNMZDTQ-UHFFFAOYSA-N 1,3a,4,5,6,7-hexahydrooxadiazolo[3,4-a]pyridin-3-one Chemical compound C1CCCC2C(=O)ONN21 JVZZMANDNMZDTQ-UHFFFAOYSA-N 0.000 description 1
• FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
• MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
• NZAXGZYPZGEVBD-UHFFFAOYSA-N 1-benzoylpiperidin-4-one Chemical compound C=1C=CC=CC=1C(=O)N1CCC(=O)CC1 NZAXGZYPZGEVBD-UHFFFAOYSA-N 0.000 description 1
• FGYADSCZTQOAFK-UHFFFAOYSA-N 1-methylbenzimidazole Chemical compound C1=CC=C2N(C)C=NC2=C1 FGYADSCZTQOAFK-UHFFFAOYSA-N 0.000 description 1
• 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
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• 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
• 125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 description 1
• 238000006664 bond formation reaction Methods 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
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• 239000003153 chemical reaction reagent Substances 0.000 description 1
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• OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
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• 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
• SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
• MBWXLICVQZUJOW-UHFFFAOYSA-N diethyl 1h-pyrazole-3,5-dicarboxylate Chemical compound CCOC(=O)C=1C=C(C(=O)OCC)NN=1 MBWXLICVQZUJOW-UHFFFAOYSA-N 0.000 description 1
• WMRCWTOZPXQBML-UHFFFAOYSA-N diethyl 6,7-dihydro-4H-thieno[3,2-c]pyridine-2,5-dicarboxylate (5-methyl-6,7-dihydro-4H-thieno[3,2-c]pyridin-2-yl)methanol Chemical compound C(C)OC(=O)C1=CC=2CN(CCC2S1)C(=O)OCC.CN1CC2=C(CC1)SC(=C2)CO WMRCWTOZPXQBML-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
• 125000004582 dihydrobenzothienyl group Chemical group S1C(CC2=C1C=CC=C2)* 0.000 description 1
• 125000005435 dihydrobenzoxazolyl group Chemical group O1C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
• 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000005049 dihydrooxadiazolyl group Chemical group O1N(NC=C1)* 0.000 description 1
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• 238000010790 dilution Methods 0.000 description 1
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• PQXBANOECKRHSY-UHFFFAOYSA-N ethyl 1H-pyrrolo[1,2-b]pyrazole-2-carboxylate Chemical compound CCOC(=O)C1=CC2=CC=CN2N1 PQXBANOECKRHSY-UHFFFAOYSA-N 0.000 description 1
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• KMFZQXAMIWKYMU-UHFFFAOYSA-N ethyl 2-formyl-6,7-dihydro-4H-thieno[3,2-c]pyridine-5-carboxylate 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O.CCOC(=O)N1CCc2sc(C=O)cc2C1 KMFZQXAMIWKYMU-UHFFFAOYSA-N 0.000 description 1
• UYYNSVHJHJUZRY-UHFFFAOYSA-N ethyl 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-3-carboxylate Chemical compound C1CCCC2=C(C(=O)OCC)C=NN21 UYYNSVHJHJUZRY-UHFFFAOYSA-N 0.000 description 1
• YTYJZXFCWYHVPG-UHFFFAOYSA-N ethyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxylate Chemical compound C1CNCC2=NC(C(=O)OCC)=CN21 YTYJZXFCWYHVPG-UHFFFAOYSA-N 0.000 description 1
• UVYMXIAFTVXRIT-UHFFFAOYSA-N ethyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxylate;dihydrochloride Chemical compound Cl.Cl.C1CNCC2=NC(C(=O)OCC)=CN21 UVYMXIAFTVXRIT-UHFFFAOYSA-N 0.000 description 1
• QXVVXFZKXXPMCZ-UHFFFAOYSA-N ethyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxylate;hydrochloride Chemical compound Cl.C1CNCC2=NC(C(=O)OCC)=CN21 QXVVXFZKXXPMCZ-UHFFFAOYSA-N 0.000 description 1
• OXKHHZJNEHYAPB-UHFFFAOYSA-N ethyl 6,7-dihydro-4h-pyrazolo[5,1-c][1,4]oxazine-2-carboxylate Chemical compound C1OCCN2N=C(C(=O)OCC)C=C21 OXKHHZJNEHYAPB-UHFFFAOYSA-N 0.000 description 1
• XCDXZBOCFHTGBZ-UHFFFAOYSA-N ethyl 6,7-dihydro-4h-pyrazolo[5,1-c][1,4]thiazine-2-carboxylate Chemical compound C1SCCN2N=C(C(=O)OCC)C=C21 XCDXZBOCFHTGBZ-UHFFFAOYSA-N 0.000 description 1
• ATCYUSYVYTVRCH-UHFFFAOYSA-N ethyl 6,7-dihydro-4h-thieno[3,2-c]thiopyran-2-carboxylate Chemical compound C1SCCC2=C1C=C(C(=O)OCC)S2 ATCYUSYVYTVRCH-UHFFFAOYSA-N 0.000 description 1
• MFJQBPOGFVVDAN-UHFFFAOYSA-N ethyl 6,7-dihydro-5h-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate Chemical compound O1CCCN2N=C(C(=O)OCC)C=C21 MFJQBPOGFVVDAN-UHFFFAOYSA-N 0.000 description 1
• DEQZHPHBXYMRRM-UHFFFAOYSA-N ethyl 7-methyl-6,8-dihydro-5h-imidazo[1,2-a]pyrazine-2-carboxylate Chemical compound C1CN(C)CC2=NC(C(=O)OCC)=CN21 DEQZHPHBXYMRRM-UHFFFAOYSA-N 0.000 description 1
• SWABYVXORFBBAT-UHFFFAOYSA-N ethyl imidazo[1,2-a]pyrazine-2-carboxylate Chemical compound C1=CN=CC2=NC(C(=O)OCC)=CN21 SWABYVXORFBBAT-UHFFFAOYSA-N 0.000 description 1
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• SZYQPTAROQANMV-UHFFFAOYSA-N ethyl pyrazine-2-carboxylate Chemical compound CCOC(=O)C1=CN=CC=N1 SZYQPTAROQANMV-UHFFFAOYSA-N 0.000 description 1
• SKLAKYXLYZIYND-UHFFFAOYSA-N ethyl pyrazine-2-carboxylate hydrochloride Chemical compound Cl.CCOC(=O)C1=CN=CC=N1 SKLAKYXLYZIYND-UHFFFAOYSA-N 0.000 description 1
• 238000011156 evaluation Methods 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• RZTAMFZIAATZDJ-UHFFFAOYSA-N felodipine Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-UHFFFAOYSA-N 0.000 description 1
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• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
• HKIOYBQGHSTUDB-UHFFFAOYSA-N folpet Chemical group C1=CC=C2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C2=C1 HKIOYBQGHSTUDB-UHFFFAOYSA-N 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 238000005194 fractionation Methods 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 244000000058 gram-negative pathogen Species 0.000 description 1
• 244000000059 gram-positive pathogen Species 0.000 description 1
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
• 125000005114 heteroarylalkoxy group Chemical group 0.000 description 1
• 125000005367 heteroarylalkylthio group Chemical group 0.000 description 1
• 125000005368 heteroarylthio group Chemical group 0.000 description 1
• 150000002430 hydrocarbons Chemical group 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• WNSDZBQLMGKPQS-UHFFFAOYSA-N hydron;piperazine-2-carboxylic acid;dichloride Chemical compound Cl.Cl.OC(=O)C1CNCCN1 WNSDZBQLMGKPQS-UHFFFAOYSA-N 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• UWNADWZGEHDQAB-UHFFFAOYSA-N i-Pr2C2H4i-Pr2 Natural products CC(C)CCC(C)C UWNADWZGEHDQAB-UHFFFAOYSA-N 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 230000002779 inactivation Effects 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 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
• 238000001802 infusion Methods 0.000 description 1
• HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
• OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 1
• 229910001623 magnesium bromide Inorganic materials 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
• CJLTWDSFHRZENM-UHFFFAOYSA-N methyl 2-formyl-5,7-dihydro-4h-furo[2,3-c]pyridine-6-carboxylate Chemical compound C1N(C(=O)OC)CCC2=C1OC(C=O)=C2 CJLTWDSFHRZENM-UHFFFAOYSA-N 0.000 description 1
• BTULAIPMXDNGHB-UHFFFAOYSA-N methyl 5,6-dihydro-4h-cyclopenta[b]furan-2-carboxylate Chemical compound C1CCC2=C1C=C(C(=O)OC)O2 BTULAIPMXDNGHB-UHFFFAOYSA-N 0.000 description 1
• ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
• 238000005142 microbroth dilution method Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 description 1
• JUNOWSHJELIDQP-UHFFFAOYSA-N morpholin-4-ium-3-carboxylate Chemical compound OC(=O)C1COCCN1 JUNOWSHJELIDQP-UHFFFAOYSA-N 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 239000010502 orange oil Substances 0.000 description 1
• ZVTQYRVARPYRRE-UHFFFAOYSA-N oxadiazol-4-one Chemical compound O=C1CON=N1 ZVTQYRVARPYRRE-UHFFFAOYSA-N 0.000 description 1
• NYSSRYDWEDXXBC-UHFFFAOYSA-N oxazin-2-ylmethanol Chemical compound O1N(C=CC=C1)CO NYSSRYDWEDXXBC-UHFFFAOYSA-N 0.000 description 1
• MTYYIWGKIVFIMX-UHFFFAOYSA-N oxazine-2-carboxylic acid Chemical compound OC(=O)N1OC=CC=C1 MTYYIWGKIVFIMX-UHFFFAOYSA-N 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 150000002960 penicillins Chemical class 0.000 description 1
• 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229940002612 prodrug Drugs 0.000 description 1
• 239000000651 prodrug Substances 0.000 description 1
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
• 239000012264 purified product Substances 0.000 description 1
• XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 1
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
• NIXHWFMRYWSRCN-UHFFFAOYSA-N pyrazolo[1,5-a]pyridine-2-carbaldehyde Chemical compound C1=CC=CN2N=C(C=O)C=C21 NIXHWFMRYWSRCN-UHFFFAOYSA-N 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• OQGIABLRBFCSPN-DVLBUVSBSA-M sodium (5R,6Z)-6-[(5,5-dimethyl-4,6-dihydropyrrolo[1,2-b]pyrazol-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound CC1(CC2=CC(=NN2C1)/C=C/3\[C@@H]4N(C3=O)C(=CS4)C(=O)[O-])C.[Na+] OQGIABLRBFCSPN-DVLBUVSBSA-M 0.000 description 1
• QBQILPJCXWICHS-UYTGOYFPSA-M sodium (6Z)-6-(5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1CC2=CC(=NN2C1)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-].[Na+] QBQILPJCXWICHS-UYTGOYFPSA-M 0.000 description 1
• JNLPKXGXSAQCGN-ZTXYIFKNSA-M sodium (6Z)-6-[(7-benzyl-6,8-dihydro-5H-imidazo[1,2-a]pyrazin-2-yl)methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1CN2C=C(N=C2CN1CC3=CC=CC=C3)/C=C/4\C5N(C4=O)C(=CS5)C(=O)[O-].[Na+] JNLPKXGXSAQCGN-ZTXYIFKNSA-M 0.000 description 1
• ZTSFBZTZUWBZEH-LFYAFSDUSA-M sodium (6Z)-6-[[5-[4-[(4-nitrophenyl)methoxy]-4-oxobutanoyl]-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-2-yl]methylidene]-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1CN2C(=CC(=N2)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-])CN1C(=O)CCC(=O)OCC5=CC=C(C=C5)[N+](=O)[O-].[Na+] ZTSFBZTZUWBZEH-LFYAFSDUSA-M 0.000 description 1
• KPLQWZHWLPLTOU-WONROIIJSA-M sodium (6Z)-7-oxo-6-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1CN2C(=CC(=N2)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-])CN1.[Na+] KPLQWZHWLPLTOU-WONROIIJSA-M 0.000 description 1
• UGTMAFLDASQVJU-NGRDVXTNSA-M sodium (6Z)-7-oxo-6-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1CN2C=C(N=C2CN1)/C=C/3\C4N(C3=O)C(=CS4)C(=O)[O-].[Na+] UGTMAFLDASQVJU-NGRDVXTNSA-M 0.000 description 1
• GZYLJOOVDWDUDK-UHFFFAOYSA-M sodium 7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].O=C1CC2SC=C(N12)C(=O)[O-] GZYLJOOVDWDUDK-UHFFFAOYSA-M 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• UIPRPTNYUKOWQQ-WBFSQFMTSA-M sodium;(5r,6z)-6-(6,7-dihydro-4h-pyrazolo[5,1-c][1,4]thiazin-2-ylmethylidene)-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].C1=C2CSCCN2N=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)[O-] UIPRPTNYUKOWQQ-WBFSQFMTSA-M 0.000 description 1
• XZDJADKCMCXIOZ-DPIAUDMESA-M sodium;(5r,6z)-7-oxo-6-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-2-ylmethylidene)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [Na+].C1=C2CCCCN2N=C1/C=C1/C(=O)N2[C@@H]1SC=C2C(=O)[O-] XZDJADKCMCXIOZ-DPIAUDMESA-M 0.000 description 1
• HORSWLUVMGDZRC-UHFFFAOYSA-M sodium;bicyclo[3.2.0]hept-3-ene-4-carboxylate Chemical compound [Na+].[O-]C(=O)C1=CCC2CCC12 HORSWLUVMGDZRC-UHFFFAOYSA-M 0.000 description 1
• 238000002798 spectrophotometry method Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 125000005415 substituted alkoxy group Chemical group 0.000 description 1
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
• 150000003463 sulfur Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
• 230000002195 synergetic effect Effects 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
• ZDBZERHPDYWTBK-UHFFFAOYSA-N tert-butyl 2-(hydroxymethyl)-6,7-dihydro-4h-thieno[3,2-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1C=C(CO)S2 ZDBZERHPDYWTBK-UHFFFAOYSA-N 0.000 description 1
• RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
• POPGQGANPRFXQP-UHFFFAOYSA-N tert-butyl-dimethyl-(2-pyrazol-1-ylethoxy)silane Chemical compound CC(C)(C)[Si](C)(C)OCCN1C=CC=N1 POPGQGANPRFXQP-UHFFFAOYSA-N 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• ULSZVNJBVJWEJE-UHFFFAOYSA-N thiazolidine-2-carboxylic acid Chemical compound OC(=O)C1NCCS1 ULSZVNJBVJWEJE-UHFFFAOYSA-N 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 238000011200 topical administration Methods 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1