HU183006B

HU183006B - Process for producing 7-substituted-3-cepheme- and cephame-4-carboxylic acid derivatives

Process for producing 7-substituted-3-cepheme- and cephame-4-carboxylic acid derivatives Download PDF

Info

Publication number: HU183006B
Authority: HU; Hungary
Prior art keywords: alkyl; amino; thiadiazol; carboxylic acid; acetamido
Prior art date: 1978-12-29

Application number

HU79FU382A

Other languages

English (en)

Hungarian (hu)

Inventor

Tsutomu Teraji

Kazuo Sakane

Jiro Goto

Original Assignee

Fujisawa Pharmaceutical Co

Priority date

1978-12-29

Filing date

1979-12-28

Publication date

1984-04-28

1979-12-28 Application filed by Fujisawa Pharmaceutical Co filed Critical Fujisawa Pharmaceutical Co

1984-01-13 Priority claimed from AU23283/84A external-priority patent/AU2328384A/en

1984-04-28 Publication of HU183006B publication Critical patent/HU183006B/hu

Links

238000000034 method Methods 0.000 title claims description 87
-1 amino, protected amino Chemical group 0.000 claims abstract description 967
150000001875 compounds Chemical class 0.000 claims abstract description 223
125000000217 alkyl group Chemical group 0.000 claims abstract description 140
238000002360 preparation method Methods 0.000 claims abstract description 64
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 43
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 claims abstract description 12
125000004423 acyloxy group Chemical group 0.000 claims abstract description 8
125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
239000000463 material Substances 0.000 claims abstract description 6
JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims abstract description 4
239000000243 solution Substances 0.000 claims description 137
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 136
150000003839 salts Chemical class 0.000 claims description 124
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 45
125000006239 protecting group Chemical group 0.000 claims description 32
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 13
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
239000003795 chemical substances by application Substances 0.000 claims description 11
125000004942 pyridazin-6-yl group Chemical group N1=NC=CC=C1* 0.000 claims description 11
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 8
150000002367 halogens Chemical group 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
239000000126 substance Substances 0.000 claims description 8
125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 7
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
VJHTZTZXOKVQRN-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine Chemical compound NC1=NC=NS1 VJHTZTZXOKVQRN-UHFFFAOYSA-N 0.000 claims description 7
125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
125000004442 acylamino group Chemical group 0.000 claims description 4
125000005236 alkanoylamino group Chemical group 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
206010029897 Obsessive thoughts Diseases 0.000 claims description 3
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
AOKKGXXYBPBKDR-UHFFFAOYSA-N 1-methyl-2h-tetrazol-5-one Chemical compound CN1N=NN=C1O AOKKGXXYBPBKDR-UHFFFAOYSA-N 0.000 claims description 2
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
239000000654 additive Substances 0.000 claims description 2
125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
239000002775 capsule Substances 0.000 claims description 2
239000008298 dragée Substances 0.000 claims description 2
239000000839 emulsion Substances 0.000 claims description 2
125000004193 piperazinyl group Chemical group 0.000 claims description 2
239000000829 suppository Substances 0.000 claims description 2
239000003826 tablet Substances 0.000 claims description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 4
125000003710 aryl alkyl group Chemical group 0.000 claims 1
125000000392 cycloalkenyl group Chemical group 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
239000004009 herbicide Substances 0.000 claims 1
238000002347 injection Methods 0.000 claims 1
239000007924 injection Substances 0.000 claims 1
150000008048 phenylpyrazoles Chemical class 0.000 claims 1
239000006187 pill Substances 0.000 claims 1
UGZVCHWAXABBHR-UHFFFAOYSA-O pyridin-1-ium-1-carboxamide Chemical class NC(=O)[N+]1=CC=CC=C1 UGZVCHWAXABBHR-UHFFFAOYSA-O 0.000 claims 1
239000002002 slurry Substances 0.000 claims 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 claims 1
125000001166 thiolanyl group Chemical group 0.000 claims 1
125000003277 amino group Chemical group 0.000 abstract description 11
125000003118 aryl group Chemical group 0.000 abstract description 7
125000002252 acyl group Chemical group 0.000 abstract description 5
230000000844 anti-bacterial effect Effects 0.000 abstract description 3
241000894006 Bacteria Species 0.000 abstract description 2
125000000753 cycloalkyl group Chemical group 0.000 abstract description 2
238000000354 decomposition reaction Methods 0.000 description 614
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 285
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 244
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 220
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 198
238000005481 NMR spectroscopy Methods 0.000 description 180
239000000203 mixture Substances 0.000 description 172
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 167
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 141
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 127
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
238000006243 chemical reaction Methods 0.000 description 96
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 81
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 78
238000002329 infrared spectrum Methods 0.000 description 78
239000002253 acid Substances 0.000 description 74
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
239000000843 powder Substances 0.000 description 64
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 55
239000011541 reaction mixture Substances 0.000 description 55
239000002244 precipitate Substances 0.000 description 48
238000004519 manufacturing process Methods 0.000 description 45
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 42
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
238000001914 filtration Methods 0.000 description 41
229910000030 sodium bicarbonate Inorganic materials 0.000 description 39
235000017557 sodium bicarbonate Nutrition 0.000 description 39
239000002904 solvent Substances 0.000 description 37
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
239000000706 filtrate Substances 0.000 description 32
229960000583 acetic acid Drugs 0.000 description 30
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 30
125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 description 29
239000008346 aqueous phase Substances 0.000 description 28
239000000284 extract Substances 0.000 description 28
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 24
150000002148 esters Chemical class 0.000 description 24
239000000047 product Substances 0.000 description 24
238000003756 stirring Methods 0.000 description 22
229910052943 magnesium sulfate Inorganic materials 0.000 description 21
235000019341 magnesium sulphate Nutrition 0.000 description 21
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
239000002585 base Substances 0.000 description 18
238000001816 cooling Methods 0.000 description 18
230000002829 reductive effect Effects 0.000 description 18
239000007864 aqueous solution Substances 0.000 description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
229910052783 alkali metal Inorganic materials 0.000 description 14
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 13
235000011054 acetic acid Nutrition 0.000 description 13
WFDIJRYMOXRFFG-UHFFFAOYSA-N acetic acid anhydride Natural products CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 13
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 12
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 12
238000005406 washing Methods 0.000 description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
238000010438 heat treatment Methods 0.000 description 11
239000002198 insoluble material Substances 0.000 description 11
239000010410 layer Substances 0.000 description 11
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 10
235000019253 formic acid Nutrition 0.000 description 10
229910052751 metal Inorganic materials 0.000 description 10
239000002184 metal Substances 0.000 description 10
LWFWUJCJKPUZLV-UHFFFAOYSA-N n-trimethylsilylacetamide Chemical compound CC(=O)N[Si](C)(C)C LWFWUJCJKPUZLV-UHFFFAOYSA-N 0.000 description 10
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 10
IKWLIQXIPRUIDU-ZCFIWIBFSA-N (6r)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CCS[C@@H]2CC(=O)N12 IKWLIQXIPRUIDU-ZCFIWIBFSA-N 0.000 description 9
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
230000007062 hydrolysis Effects 0.000 description 9
238000006460 hydrolysis reaction Methods 0.000 description 9
239000005457 ice water Substances 0.000 description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
229920005989 resin Polymers 0.000 description 9
239000011347 resin Substances 0.000 description 9
239000011734 sodium Substances 0.000 description 9
MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
238000003776 cleavage reaction Methods 0.000 description 8
238000004440 column chromatography Methods 0.000 description 8
239000012043 crude product Substances 0.000 description 8
238000001035 drying Methods 0.000 description 8
150000007522 mineralic acids Chemical class 0.000 description 8
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
125000001424 substituent group Chemical group 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 7
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 7
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 7
150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
150000007529 inorganic bases Chemical class 0.000 description 7
150000007524 organic acids Chemical class 0.000 description 7
150000007530 organic bases Chemical class 0.000 description 7
239000012071 phase Substances 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
229910052708 sodium Inorganic materials 0.000 description 7
238000001228 spectrum Methods 0.000 description 7
238000001665 trituration Methods 0.000 description 7
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 6
PNRDWLQUFXLAFG-LNUXAPHWSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopentyloxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1(CCCC1)ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N PNRDWLQUFXLAFG-LNUXAPHWSA-N 0.000 description 6
125000004515 1,2,4-thiadiazol-3-yl group Chemical group S1N=C(N=C1)* 0.000 description 6
OVZHELCFKSFINS-UHFFFAOYSA-N 3h-1,3,4-thiadiazol-2-one Chemical compound O=C1NN=CS1 OVZHELCFKSFINS-UHFFFAOYSA-N 0.000 description 6
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
229910052784 alkaline earth metal Inorganic materials 0.000 description 6
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
238000010992 reflux Methods 0.000 description 6
239000007858 starting material Substances 0.000 description 6
FZDRVLJSDYQRPO-HWZXHQHMSA-N (6r)-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CC(C)S[C@@H]2CC(=O)N21 FZDRVLJSDYQRPO-HWZXHQHMSA-N 0.000 description 5
KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 5
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
238000006722 reduction reaction Methods 0.000 description 5
GCQUZKXRJRPLCV-UHFFFAOYSA-N 1-prop-2-enyltetrazole Chemical compound C=CCN1C=NN=N1 GCQUZKXRJRPLCV-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 4
238000004566 IR spectroscopy Methods 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
150000008065 acid anhydrides Chemical class 0.000 description 4
229910000288 alkali metal carbonate Inorganic materials 0.000 description 4
150000008041 alkali metal carbonates Chemical class 0.000 description 4
150000008044 alkali metal hydroxides Chemical class 0.000 description 4
150000001340 alkali metals Chemical class 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
150000003863 ammonium salts Chemical class 0.000 description 4
239000012267 brine Substances 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
238000010908 decantation Methods 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
239000000796 flavoring agent Substances 0.000 description 4
235000019634 flavors Nutrition 0.000 description 4
238000004108 freeze drying Methods 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
239000007788 liquid Substances 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
239000008363 phosphate buffer Substances 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
239000011591 potassium Substances 0.000 description 4
229960003975 potassium Drugs 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
235000011181 potassium carbonates Nutrition 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
238000001179 sorption measurement Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
125000005270 trialkylamine group Chemical group 0.000 description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
GAOJHQWQCQWSDH-PLNQYNMKSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(carboxymethoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(=O)(O)CON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N GAOJHQWQCQWSDH-PLNQYNMKSA-N 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 3
YLFZQLDHKKLIEL-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-phenoxyiminoacetic acid Chemical compound S1C(N)=NC(C(=NOC=2C=CC=CC=2)C(O)=O)=N1 YLFZQLDHKKLIEL-UHFFFAOYSA-N 0.000 description 3
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 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
125000004466 alkoxycarbonylamino group Chemical group 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
238000009835 boiling Methods 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
239000011575 calcium Substances 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
125000001841 imino group Chemical group [H]N=* 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
159000000003 magnesium salts Chemical class 0.000 description 3
HUTKBOFGPQYVEI-UHFFFAOYSA-N methyl 5-amino-1,2,4-thiadiazole-3-carboxylate Chemical compound COC(=O)C1=NSC(N)=N1 HUTKBOFGPQYVEI-UHFFFAOYSA-N 0.000 description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 3
229940116357 potassium thiocyanate Drugs 0.000 description 3
230000007017 scission Effects 0.000 description 3
239000007787 solid Substances 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
239000011701 zinc Substances 0.000 description 3
229910052725 zinc Inorganic materials 0.000 description 3
WXTLQWGVFOFOBP-LMNIDFBRSA-N (4-nitrophenyl)methyl (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(4-chlorophenoxy)iminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound ClC1=CC=C(ON=C(C(=O)NC2[C@@H]3N(C(=CCS3)C(=O)OCC3=CC=C(C=C3)[N+](=O)[O-])C2=O)C2=NSC(=N2)N)C=C1 WXTLQWGVFOFOBP-LMNIDFBRSA-N 0.000 description 2
FMNWHQIIAWLYQL-RKSKCOGQSA-N (6R)-7-[[2-(3-aminopropoxyimino)-2-(5-amino-1,2,4-thiadiazol-3-yl)acetyl]amino]-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NCCCON=C(C(=O)NC1[C@@H]2N(C(=C(CS2)Cl)C(=O)O)C1=O)C1=NSC(=N1)N FMNWHQIIAWLYQL-RKSKCOGQSA-N 0.000 description 2
AMWZNBRDQDIYKJ-BUDIUTNSSA-N (6R)-7-[[2-(3-aminopropoxyimino)-2-(5-amino-1,2,4-thiadiazol-3-yl)acetyl]amino]-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NCCCON=C(C(=O)NC1[C@@H]2N(C(=CC(S2)C)C(=O)O)C1=O)C1=NSC(=N1)N AMWZNBRDQDIYKJ-BUDIUTNSSA-N 0.000 description 2
WRZZVAUSTGNWBJ-JOPIAHFSSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(4-chlorophenoxy)iminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound ClC1=CC=C(ON=C(C(=O)NC2[C@@H]3N(C(=CCS3)C(=O)O)C2=O)C2=NSC(=N2)N)C=C1 WRZZVAUSTGNWBJ-JOPIAHFSSA-N 0.000 description 2
ODNTWRXYUSRONW-JOPIAHFSSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(4-fluorophenoxy)iminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound FC1=CC=C(ON=C(C(=O)NC2[C@@H]3N(C(=CCS3)C(=O)O)C2=O)C2=NSC(=N2)N)C=C1 ODNTWRXYUSRONW-JOPIAHFSSA-N 0.000 description 2
XCKOMYCIDDTFOQ-IUQLYUOWSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)C(C)ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N XCKOMYCIDDTFOQ-IUQLYUOWSA-N 0.000 description 2
YIYZOBLFUJJSFW-PVQCJRHBSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cycloheptyloxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1(CCCCCC1)ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N YIYZOBLFUJJSFW-PVQCJRHBSA-N 0.000 description 2
MWPFAGJEFJVZMO-IUQLYUOWSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopent-2-en-1-yloxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1(C=CCC1)ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N MWPFAGJEFJVZMO-IUQLYUOWSA-N 0.000 description 2
OBZPELDGSNYFTD-XCGJVMPOSA-N (6r)-7-amino-8-oxo-3-(1,3,4-thiadiazol-2-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S([C@@H]1C(C(N1C=1C(O)=O)=O)N)CC=1CSC1=NN=CS1 OBZPELDGSNYFTD-XCGJVMPOSA-N 0.000 description 2
RJFPBECTFIUTHB-INEUFUBQSA-N (6r,7r)-7-azaniumyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S1CC=C(C(O)=O)N2C(=O)[C@@H](N)[C@H]21 RJFPBECTFIUTHB-INEUFUBQSA-N 0.000 description 2
YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 description 2
YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 2
CZPYGXAQBZOJLI-UHFFFAOYSA-N 1-(3-aminopropyl)-2h-tetrazole-5-thione;hydrochloride Chemical compound Cl.NCCCN1N=NN=C1S CZPYGXAQBZOJLI-UHFFFAOYSA-N 0.000 description 2
OMAFFHIGWTVZOH-UHFFFAOYSA-N 1-methyltetrazole Chemical compound CN1C=NN=N1 OMAFFHIGWTVZOH-UHFFFAOYSA-N 0.000 description 2
AYTOSMACNLSHJY-UHFFFAOYSA-N 2-(2-oxooxolan-3-yl)oxyisoindole-1,3-dione Chemical compound O=C1OCCC1ON1C(=O)C2=CC=CC=C2C1=O AYTOSMACNLSHJY-UHFFFAOYSA-N 0.000 description 2
XSZNJFMXRLMYIJ-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(4-chlorophenoxy)iminoacetic acid Chemical compound S1C(N)=NC(C(=NOC=2C=CC(Cl)=CC=2)C(O)=O)=N1 XSZNJFMXRLMYIJ-UHFFFAOYSA-N 0.000 description 2
IYRMJNCXBWNYPM-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(4-fluorophenoxy)iminoacetic acid Chemical compound S1C(N)=NC(C(=NOC=2C=CC(F)=CC=2)C(O)=O)=N1 IYRMJNCXBWNYPM-UHFFFAOYSA-N 0.000 description 2
NHENVHGVMLDVPP-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopentyloxyiminoacetic acid Chemical compound S1C(N)=NC(C(=NOC2CCCC2)C(O)=O)=N1 NHENVHGVMLDVPP-UHFFFAOYSA-N 0.000 description 2
PAWLZTFPRRRKEF-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-trityloxyiminoacetic acid Chemical compound N=1SC(NC=O)=NC=1C(C(=O)O)=NOC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 PAWLZTFPRRRKEF-UHFFFAOYSA-N 0.000 description 2
YDXLUHGBGZSXJF-UHFFFAOYSA-N 2-(5-oxo-1H-tetrazol-4-yl)acetic acid Chemical compound C(=O)(O)CN1NN=NC1=O YDXLUHGBGZSXJF-UHFFFAOYSA-N 0.000 description 2
GMBXTUIJIVGYFE-UHFFFAOYSA-N 2-[3-(4-methylpiperazin-1-yl)propyl]isoindole-1,3-dione Chemical compound C1CN(C)CCN1CCCN1C(=O)C2=CC=CC=C2C1=O GMBXTUIJIVGYFE-UHFFFAOYSA-N 0.000 description 2
WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
OPZZNSQTJKVPBZ-UHFFFAOYSA-N 2-cycloheptyloxyisoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1OC1CCCCCC1 OPZZNSQTJKVPBZ-UHFFFAOYSA-N 0.000 description 2
QXFTXVXMRKJENL-UHFFFAOYSA-N 2-cyclohex-2-en-1-yloxyisoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1OC1CCCC=C1 QXFTXVXMRKJENL-UHFFFAOYSA-N 0.000 description 2
AWUATQVEDONQBX-UHFFFAOYSA-N 2-cyclopent-2-en-1-yloxyimino-2-(5-formamido-1,2,4-thiadiazol-3-yl)acetic acid Chemical compound N=1SC(NC=O)=NC=1C(C(=O)O)=NOC1CCC=C1 AWUATQVEDONQBX-UHFFFAOYSA-N 0.000 description 2
ZLZXBIRCZUAYTE-UHFFFAOYSA-N 2-cyclopent-2-en-1-yloxyisoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1OC1CCC=C1 ZLZXBIRCZUAYTE-UHFFFAOYSA-N 0.000 description 2
RQSCFNPNNLWQBJ-UHFFFAOYSA-N 2-methyl-1,3,4-thiadiazole Chemical compound CC1=NN=CS1 RQSCFNPNNLWQBJ-UHFFFAOYSA-N 0.000 description 2
LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
241000588724 Escherichia coli Species 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
229920000388 Polyphosphate Polymers 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical class C=CC1=CC=CC=C1 PPBRXRYQALVLMV-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
238000010521 absorption reaction Methods 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 2
229940077388 benzenesulfonate Drugs 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
244000309464 bull Species 0.000 description 2
OKIIEJOIXGHUKX-UHFFFAOYSA-L cadmium iodide Chemical group [Cd+2].[I-].[I-] OKIIEJOIXGHUKX-UHFFFAOYSA-L 0.000 description 2
WLXGQJPKEOLNNB-UHFFFAOYSA-N carbamoyl pyridine-4-carboxylate Chemical class NC(=O)OC(=O)C1=CC=NC=C1 WLXGQJPKEOLNNB-UHFFFAOYSA-N 0.000 description 2
125000001589 carboacyl group Chemical group 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
150000007942 carboxylates Chemical class 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
239000010949 copper Substances 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
DSHWMBCJDOGPTB-UHFFFAOYSA-N ethyl 2-ethoxy-2-iminoacetate Chemical compound CCOC(=N)C(=O)OCC DSHWMBCJDOGPTB-UHFFFAOYSA-N 0.000 description 2
MSMGXWFHBSCQFB-UHFFFAOYSA-N ethyl cyanoformate Chemical compound CCOC(=O)C#N MSMGXWFHBSCQFB-UHFFFAOYSA-N 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
208000015181 infectious disease Diseases 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
239000011630 iodine Substances 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 2
239000001095 magnesium carbonate Substances 0.000 description 2
229910000021 magnesium carbonate Inorganic materials 0.000 description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
BCUQUHMYWJUHAN-UHFFFAOYSA-N methyl 2-amino-2-oxoacetate hydrochloride Chemical compound Cl.COC(=O)C(N)=O BCUQUHMYWJUHAN-UHFFFAOYSA-N 0.000 description 2
IBZOUBJYLPFRGJ-UHFFFAOYSA-N methyl 5-formamido-1,2,4-thiadiazole-3-carboxylate Chemical compound COC(=O)C1=NSC(NC=O)=N1 IBZOUBJYLPFRGJ-UHFFFAOYSA-N 0.000 description 2
QLPLETSQYWDOIZ-UHFFFAOYSA-N methyl n-(3-acetamidopropyl)carbamodithioate Chemical compound CSC(=S)NCCCNC(C)=O QLPLETSQYWDOIZ-UHFFFAOYSA-N 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 2
239000001205 polyphosphate Substances 0.000 description 2
235000011176 polyphosphates Nutrition 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
235000015497 potassium bicarbonate Nutrition 0.000 description 2
229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
239000011736 potassium bicarbonate Substances 0.000 description 2
QCXNNLMVFYMKMH-UHFFFAOYSA-N s-methyl 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-oxoethanethioate Chemical compound CSC(=O)C(=O)C1=NSC(NC=O)=N1 QCXNNLMVFYMKMH-UHFFFAOYSA-N 0.000 description 2
239000001632 sodium acetate Substances 0.000 description 2
235000017281 sodium acetate Nutrition 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
150000003536 tetrazoles Chemical class 0.000 description 2
125000002813 thiocarbonyl group Chemical group *C(*)=S 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
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
MZTBTXMUURGGNR-GLGOKHISSA-N (4-nitrophenyl)methyl (6r)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)N)CC=C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 MZTBTXMUURGGNR-GLGOKHISSA-N 0.000 description 1
ZZJNYZZMWBXNON-SSDOTTSWSA-N (6R)-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC=1CS[C@H]2N(C=1C(=O)O)C(C2)=O ZZJNYZZMWBXNON-SSDOTTSWSA-N 0.000 description 1
HSKDXIASDIYSIU-FFFFSGIJSA-N (6R)-4-[[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]tetrazol-5-yl]sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)NCCN1N=NN=C1SCC1S[C@H]2N(C(=C1)C(=O)O)C(C2)=O HSKDXIASDIYSIU-FFFFSGIJSA-N 0.000 description 1
SJVHWOXZHOWOTA-ANXXIGAQSA-N (6R)-7-[[2-(2-aminoethoxyimino)-2-(5-amino-1,2,4-thiadiazol-3-yl)acetyl]amino]-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NCCON=C(C(=O)NC1[C@@H]2N(C(=CC(S2)C)C(=O)O)C1=O)C1=NSC(=N1)N SJVHWOXZHOWOTA-ANXXIGAQSA-N 0.000 description 1
OVWKUHASGYHFON-AZMWARKLSA-N (6R)-7-[[2-(3-aminopropoxyimino)-2-(5-amino-1,2,4-thiadiazol-3-yl)acetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NCCCON=C(C(=O)NC1[C@@H]2N(C(=C(CS2)C)C(=O)O)C1=O)C1=NSC(=N1)N OVWKUHASGYHFON-AZMWARKLSA-N 0.000 description 1
NMWIHXUEIDBXDY-GZYXIPPBSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-butoxy-1-oxopropan-2-yl)oxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(CCC)OC(=O)C(C)ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N NMWIHXUEIDBXDY-GZYXIPPBSA-N 0.000 description 1
BIJCJJCDGHUWIW-JOPIAHFSSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2,4-dichlorophenoxy)iminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound ClC1=C(ON=C(C(=O)NC2[C@@H]3N(C(=CCS3)C(=O)O)C2=O)C2=NSC(=N2)N)C=CC(=C1)Cl BIJCJJCDGHUWIW-JOPIAHFSSA-N 0.000 description 1
WFQWNBMZZRQRNV-PLNQYNMKSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical class C(=O)(O)C(C)(ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N)C WFQWNBMZZRQRNV-PLNQYNMKSA-N 0.000 description 1
ZLSNAFDHHCAZCC-HYYLBULJSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-oxooxolan-3-yl)oxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound O=C1OCCC1ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N ZLSNAFDHHCAZCC-HYYLBULJSA-N 0.000 description 1
MUGNCFCZURQCDV-MGAKOFKPSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(carboxymethoxyimino)acetyl]amino]-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(=O)(O)CON=C(C(=O)NC1[C@@H]2N(C(=C(CS2)Cl)C(=O)O)C1=O)C1=NSC(=N1)N MUGNCFCZURQCDV-MGAKOFKPSA-N 0.000 description 1
WEPFDIYEICROSR-LNUXAPHWSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]iminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)CON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N WEPFDIYEICROSR-LNUXAPHWSA-N 0.000 description 1
LKOOBCTXDKSJHM-LNUXAPHWSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CC(C)(ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N)C(=O)OC(C)(C)C LKOOBCTXDKSJHM-LNUXAPHWSA-N 0.000 description 1
MVMLQMAJCNASIX-FZGCPMGESA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propoxyimino]acetyl]amino]-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(C)(C)(C)OC(=O)NCCCON=C(C(=O)NC1[C@@H]2N(C(=CC(S2)C)C(=O)O)C1=O)C1=NSC(=N1)N MVMLQMAJCNASIX-FZGCPMGESA-N 0.000 description 1
IEZUGMGKSKAFMJ-ZEPSKSRBSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[carboxy(phenyl)methoxy]iminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C(=O)(O)C(C1=CC=CC=C1)ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N IEZUGMGKSKAFMJ-ZEPSKSRBSA-N 0.000 description 1
NDQVNXVCJAZREU-GZYXIPPBSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclohex-2-en-1-yloxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1(C=CCCC1)ON=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N NDQVNXVCJAZREU-GZYXIPPBSA-N 0.000 description 1
LWIBCJRUOGMMCS-MNWKQKBLSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopentyloxyiminoacetyl]amino]-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1(CCCC1)ON=C(C(=O)NC1[C@@H]2N(C(=CC(S2)C)C(=O)O)C1=O)C1=NSC(=N1)N LWIBCJRUOGMMCS-MNWKQKBLSA-N 0.000 description 1
QUCWFIJAXPLMRX-JOPIAHFSSA-N (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-phenoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound O(C1=CC=CC=C1)N=C(C(=O)NC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O)C1=NSC(=N1)N QUCWFIJAXPLMRX-JOPIAHFSSA-N 0.000 description 1
KPFMABKZFCSDJM-XCGJVMPOSA-N (6r)-7-amino-3-ethyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(CC)=C(C(O)=O)N2C(=O)C(N)[C@@H]12 KPFMABKZFCSDJM-XCGJVMPOSA-N 0.000 description 1
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 1
OTKFCIVOVKCFHR-UHFFFAOYSA-N (Methylsulfinyl)(methylthio)methane Chemical compound CSCS(C)=O OTKFCIVOVKCFHR-UHFFFAOYSA-N 0.000 description 1
125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 description 1
KNKRKFALVUDBJE-UHFFFAOYSA-N 1,2-dichloropropane Chemical compound CC(Cl)CCl KNKRKFALVUDBJE-UHFFFAOYSA-N 0.000 description 1
YNYSMLIOWYVRLH-AXQFTJQQSA-N 1-(2-methylpropanoyloxy)ethyl (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopentyloxyiminoacetyl]amino]-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1(CCCC1)ON=C(C(=O)NC1[C@@H]2N(C(=CC(S2)C)C(=O)OC(C)OC(C(C)C)=O)C1=O)C1=NSC(=N1)N YNYSMLIOWYVRLH-AXQFTJQQSA-N 0.000 description 1
UBYWHNCWGMIGSI-UHFFFAOYSA-N 1-(3-morpholin-4-ylpropyl)-2h-tetrazole-5-thione Chemical compound SC1=NN=NN1CCCN1CCOCC1 UBYWHNCWGMIGSI-UHFFFAOYSA-N 0.000 description 1
FKKOGYUVTBFXHT-UHFFFAOYSA-N 1-(3-piperidin-1-ylpropyl)-2h-tetrazole-5-thione Chemical compound SC1=NN=NN1CCCN1CCCCC1 FKKOGYUVTBFXHT-UHFFFAOYSA-N 0.000 description 1
KFHOUKIRPZSLSJ-UHFFFAOYSA-N 1-(4-aminobutyl)-2h-tetrazole-5-thione;hydrochloride Chemical compound Cl.NCCCCN1N=NN=C1S KFHOUKIRPZSLSJ-UHFFFAOYSA-N 0.000 description 1
RJFQKUZUPYGEAE-UHFFFAOYSA-N 1-(6-aminohexyl)-2h-tetrazole-5-thione;hydrochloride Chemical compound Cl.NCCCCCCN1N=NN=C1S RJFQKUZUPYGEAE-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
ZOWVXBJYFHFRHK-OTOKDRCRSA-N 1-[[(6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopentyloxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]pyridin-1-ium-4-carboxylate Chemical compound C1(CCCC1)ON=C(C(=O)NC1[C@@H]2N(C=C(CS2)C[N+]2=CC=C(C=C2)C(=O)[O-])C1=O)C1=NSC(=N1)N ZOWVXBJYFHFRHK-OTOKDRCRSA-N 0.000 description 1
AQFQTFBZSZLIIF-BAKRKDLYSA-N 1-benzoyloxyethyl (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopent-2-en-1-yloxyiminoacetyl]amino]-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1(C=CCC1)ON=C(C(=O)NC1[C@@H]2N(C(=CC(S2)C)C(=O)OC(C)OC(C2=CC=CC=C2)=O)C1=O)C1=NSC(=N1)N AQFQTFBZSZLIIF-BAKRKDLYSA-N 0.000 description 1
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 1
SNUSZUYTMHKCPM-UHFFFAOYSA-N 1-hydroxypyridin-2-one Chemical compound ON1C=CC=CC1=O SNUSZUYTMHKCPM-UHFFFAOYSA-N 0.000 description 1
YQQSRZSUGBETRS-UHFFFAOYSA-N 1h-pyridazine-6-thione Chemical compound SC1=CC=CN=N1 YQQSRZSUGBETRS-UHFFFAOYSA-N 0.000 description 1
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
BUMLSYCPHGKGFU-UHFFFAOYSA-N 2,2-bis(trimethylsilyl)acetic acid Chemical compound C[Si](C)(C)C(C(O)=O)[Si](C)(C)C BUMLSYCPHGKGFU-UHFFFAOYSA-N 0.000 description 1
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 1
WHQOKFZWSDOTQP-UHFFFAOYSA-N 2,3-dihydroxypropyl 4-aminobenzoate Chemical compound NC1=CC=C(C(=O)OCC(O)CO)C=C1 WHQOKFZWSDOTQP-UHFFFAOYSA-N 0.000 description 1
ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
BSWWXRFVMJHFBN-UHFFFAOYSA-N 2,4,6-tribromophenol Chemical compound OC1=C(Br)C=C(Br)C=C1Br BSWWXRFVMJHFBN-UHFFFAOYSA-N 0.000 description 1
NHTRUFMDWHHWSN-UHFFFAOYSA-N 2-(1-aminocyclohexyl)acetyl chloride;hydrochloride Chemical compound Cl.ClC(=O)CC1(N)CCCCC1 NHTRUFMDWHHWSN-UHFFFAOYSA-N 0.000 description 1
KAHYXMVUTQNSKN-UHFFFAOYSA-N 2-(2,2,2-trifluoroethoxy)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(OCC(F)(F)F)C(=O)C2=C1 KAHYXMVUTQNSKN-UHFFFAOYSA-N 0.000 description 1
KTNUAPFBOFMOED-UHFFFAOYSA-N 2-(2,2-dichloroacetyl)oxyimino-2-(5-formamido-1,2,4-thiadiazol-3-yl)acetic acid Chemical compound ClC(Cl)C(=O)ON=C(C(=O)O)C1=NSC(NC=O)=N1 KTNUAPFBOFMOED-UHFFFAOYSA-N 0.000 description 1
VKJCJJYNVIYVQR-UHFFFAOYSA-N 2-(3-bromopropyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCCBr)C(=O)C2=C1 VKJCJJYNVIYVQR-UHFFFAOYSA-N 0.000 description 1
ITSOTHGNWWWRGY-UHFFFAOYSA-N 2-(4-chlorophenoxy)imino-2-(5-formamido-1,2,4-thiadiazol-3-yl)acetic acid Chemical compound N=1SC(NC=O)=NC=1C(C(=O)O)=NOC1=CC=C(Cl)C=C1 ITSOTHGNWWWRGY-UHFFFAOYSA-N 0.000 description 1
HBJZQUOXCNYJOA-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-butoxy-1-oxopropan-2-yl)oxyiminoacetic acid Chemical compound CCCCOC(=O)C(C)ON=C(C(O)=O)C1=NSC(N)=N1 HBJZQUOXCNYJOA-UHFFFAOYSA-N 0.000 description 1
KUAPWUYBDXECEF-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-cyclohexyloxy-1-oxopropan-2-yl)oxyiminoacetic acid Chemical compound C1(CCCCC1)OC(=O)C(C)ON=C(C(=O)O)C1=NSC(=N1)N KUAPWUYBDXECEF-UHFFFAOYSA-N 0.000 description 1
DXXWHLZECZQSKL-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-ethoxy-2-methyl-1-oxopropan-2-yl)oxyiminoacetic acid Chemical compound CCOC(=O)C(C)(C)ON=C(C(O)=O)C1=NSC(N)=N1 DXXWHLZECZQSKL-UHFFFAOYSA-N 0.000 description 1
YSKYKBGACLNRCL-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-oxo-1-phenylmethoxypropan-2-yl)oxyiminoacetic acid Chemical compound C=1C=CC=CC=1COC(=O)C(C)ON=C(C(O)=O)C1=NSC(N)=N1 YSKYKBGACLNRCL-UHFFFAOYSA-N 0.000 description 1
JUCDUEVBKMIWAD-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-phenylethoxyimino)acetic acid Chemical compound C=1C=CC=CC=1C(C)ON=C(C(O)=O)C1=NSC(N)=N1 JUCDUEVBKMIWAD-UHFFFAOYSA-N 0.000 description 1
WHOOZVXHOKXKOL-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2,2,2-trifluoroethoxyimino)acetic acid Chemical compound NC1=NC(C(=NOCC(F)(F)F)C(O)=O)=NS1 WHOOZVXHOKXKOL-UHFFFAOYSA-N 0.000 description 1
LJPLLRRQIPACKW-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-methoxy-5-nitrophenoxy)iminoacetic acid Chemical compound COC1=CC=C([N+]([O-])=O)C=C1ON=C(C(O)=O)C1=NSC(N)=N1 LJPLLRRQIPACKW-UHFFFAOYSA-N 0.000 description 1
QUCARRIIFGUXJV-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-phenoxyethoxyimino)acetic acid Chemical compound S1C(N)=NC(C(=NOCCOC=2C=CC=CC=2)C(O)=O)=N1 QUCARRIIFGUXJV-UHFFFAOYSA-N 0.000 description 1
QJNZIFYUIAFUSY-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(3,4-dichlorophenoxy)iminoacetic acid Chemical compound S1C(N)=NC(C(=NOC=2C=C(Cl)C(Cl)=CC=2)C(O)=O)=N1 QJNZIFYUIAFUSY-UHFFFAOYSA-N 0.000 description 1
SVOYHIABPDHEJN-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(3-ethoxycarbonylphenoxy)iminoacetic acid Chemical compound CCOC(=O)C1=CC=CC(ON=C(C(O)=O)C=2N=C(N)SN=2)=C1 SVOYHIABPDHEJN-UHFFFAOYSA-N 0.000 description 1
TYHGVCZJKCAIHW-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(cyanomethoxyimino)acetic acid Chemical compound NC1=NC(C(=NOCC#N)C(O)=O)=NS1 TYHGVCZJKCAIHW-UHFFFAOYSA-N 0.000 description 1
LWMTVRPVXOJJPM-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[1-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]oxyiminoacetic acid Chemical compound CC(C)(C)OC(=O)C(CC)ON=C(C(O)=O)C1=NSC(N)=N1 LWMTVRPVXOJJPM-UHFFFAOYSA-N 0.000 description 1
GUOXKKFLWOAPBV-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetic acid Chemical compound CC(C)(C)OC(=O)C(C)ON=C(C(O)=O)C1=NSC(N)=N1 GUOXKKFLWOAPBV-UHFFFAOYSA-N 0.000 description 1
YOSFGDLBDAFZMZ-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]iminoacetic acid Chemical compound CC(C)(C)OC(=O)CON=C(C(O)=O)C1=NSC(N)=N1 YOSFGDLBDAFZMZ-UHFFFAOYSA-N 0.000 description 1
BWCJDZVONAOWHO-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[2-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]oxyiminoacetic acid Chemical compound CC(C)(C)OC(=O)C(C)(C)ON=C(C(O)=O)C1=NSC(N)=N1 BWCJDZVONAOWHO-UHFFFAOYSA-N 0.000 description 1
KJOFLRBHJINKEE-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-[3-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]oxyiminoacetic acid Chemical compound CC(C)(C)OC(=O)C(C(C)C)ON=C(C(O)=O)C1=NSC(N)=N1 KJOFLRBHJINKEE-UHFFFAOYSA-N 0.000 description 1
KTDABQPVXDDUPL-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclohex-2-en-1-yloxyiminoacetic acid Chemical compound S1C(N)=NC(C(=NOC2C=CCCC2)C(O)=O)=N1 KTDABQPVXDDUPL-UHFFFAOYSA-N 0.000 description 1
ILMAMFYUYRGJBB-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopent-2-en-1-yloxyiminoacetic acid Chemical compound S1C(N)=NC(C(=NOC2C=CCC2)C(O)=O)=N1 ILMAMFYUYRGJBB-UHFFFAOYSA-N 0.000 description 1
YYCLCUGRLMGKHU-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-hydroxyiminoacetic acid Chemical compound NC1=NC(C(=NO)C(O)=O)=NS1 YYCLCUGRLMGKHU-UHFFFAOYSA-N 0.000 description 1
BCGRNMNSZMRBST-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-phenylmethoxyiminoacetic acid Chemical compound S1C(N)=NC(C(=NOCC=2C=CC=CC=2)C(O)=O)=N1 BCGRNMNSZMRBST-UHFFFAOYSA-N 0.000 description 1
DIUMJILQVJWZRI-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-trityloxyiminoacetic acid Chemical compound S1C(N)=NC(C(=NOC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)C(O)=O)=N1 DIUMJILQVJWZRI-UHFFFAOYSA-N 0.000 description 1
XHOKMAVHTMMXSX-UHFFFAOYSA-N 2-(5-amino-1,2,4-thiadiazol-3-yl)acetamide Chemical compound NC(=O)CC1=NSC(N)=N1 XHOKMAVHTMMXSX-UHFFFAOYSA-N 0.000 description 1
DKGUFYYYADRJKR-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-(1-phenylethoxyimino)acetic acid Chemical compound C=1C=CC=CC=1C(C)ON=C(C(O)=O)C1=NSC(NC=O)=N1 DKGUFYYYADRJKR-UHFFFAOYSA-N 0.000 description 1
LEFSUHPWNFSUKO-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-(2,2,2-trifluoroethoxyimino)acetic acid Chemical compound FC(F)(F)CON=C(C(=O)O)C1=NSC(NC=O)=N1 LEFSUHPWNFSUKO-UHFFFAOYSA-N 0.000 description 1
GZPTXWFMCVYRPS-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-(2-methylsulfanylethoxyimino)acetic acid Chemical compound CSCCON=C(C(O)=O)C1=NSC(NC=O)=N1 GZPTXWFMCVYRPS-UHFFFAOYSA-N 0.000 description 1
KYPBBBBIZMUHDR-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-(2-phenoxyethoxyimino)acetic acid Chemical compound N=1SC(NC=O)=NC=1C(C(=O)O)=NOCCOC1=CC=CC=C1 KYPBBBBIZMUHDR-UHFFFAOYSA-N 0.000 description 1
HUBRXSRIFXDVLY-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-(methylsulfanylmethoxyimino)acetic acid Chemical compound CSCON=C(C(O)=O)C1=NSC(NC=O)=N1 HUBRXSRIFXDVLY-UHFFFAOYSA-N 0.000 description 1
WRRWQENLLWDICK-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propoxyimino]acetic acid Chemical compound CC(C)(C)OC(=O)NCCCON=C(C(O)=O)C1=NSC(NC=O)=N1 WRRWQENLLWDICK-UHFFFAOYSA-N 0.000 description 1
AQYXQVLUCWJHSR-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-hydroxyiminoacetic acid Chemical compound ON=C(C(O)=O)C1=NSC(NC=O)=N1 AQYXQVLUCWJHSR-UHFFFAOYSA-N 0.000 description 1
ZUIMBDWYJWDDRB-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-oxoacetic acid Chemical compound OC(=O)C(=O)C1=NSC(NC=O)=N1 ZUIMBDWYJWDDRB-UHFFFAOYSA-N 0.000 description 1
HFXDJIFGYUDJQK-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-phenoxyiminoacetic acid Chemical compound N=1SC(NC=O)=NC=1C(C(=O)O)=NOC1=CC=CC=C1 HFXDJIFGYUDJQK-UHFFFAOYSA-N 0.000 description 1
QHSRDOBLNZNPLE-UHFFFAOYSA-N 2-(5-formamido-1,2,4-thiadiazol-3-yl)-2-prop-2-ynoxyiminoacetic acid Chemical compound C#CCON=C(C(=O)O)C1=NSC(NC=O)=N1 QHSRDOBLNZNPLE-UHFFFAOYSA-N 0.000 description 1
ZGHVPBISEIPFJS-UHFFFAOYSA-N 2-(tetrazol-1-yl)ethanamine Chemical compound NCCN1C=NN=N1 ZGHVPBISEIPFJS-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
OONCSNQDICXASE-UHFFFAOYSA-N 2-[3-(1,3-dioxoisoindol-2-yl)oxypropyl]isoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCCON1C(=O)C2=CC=CC=C2C1=O OONCSNQDICXASE-UHFFFAOYSA-N 0.000 description 1
FVJFUZSJFAXEDW-UHFFFAOYSA-N 2-[[(5-amino-1,2,4-thiadiazol-3-yl)-carboxymethylidene]amino]oxy-4-hydroxybutanoic acid Chemical compound NC1=NC(C(=NOC(CCO)C(O)=O)C(O)=O)=NS1 FVJFUZSJFAXEDW-UHFFFAOYSA-N 0.000 description 1
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 1
AUSSSLJBQOCAAZ-UHFFFAOYSA-N 2-aminooxy-4-hydroxybutanoic acid Chemical compound NOC(C(O)=O)CCO AUSSSLJBQOCAAZ-UHFFFAOYSA-N 0.000 description 1
DTNSDCJFTHMDAK-UHFFFAOYSA-N 2-cyanobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C#N DTNSDCJFTHMDAK-UHFFFAOYSA-N 0.000 description 1
UWKURCIKZSHNDT-UHFFFAOYSA-N 2-cycloheptyloxyimino-2-(5-formamido-1,2,4-thiadiazol-3-yl)acetic acid Chemical compound N=1SC(NC=O)=NC=1C(C(=O)O)=NOC1CCCCCC1 UWKURCIKZSHNDT-UHFFFAOYSA-N 0.000 description 1
JXNNFSNVJZIGAA-UHFFFAOYSA-N 2-cyclohex-2-en-1-yloxyimino-2-(5-formamido-1,2,4-thiadiazol-3-yl)acetic acid Chemical compound N=1SC(NC=O)=NC=1C(C(=O)O)=NOC1CCCC=C1 JXNNFSNVJZIGAA-UHFFFAOYSA-N 0.000 description 1
FYCAOIPIRIEEGB-UHFFFAOYSA-N 2-cyclopentyloxyimino-2-(5-formamido-1,2,4-thiadiazol-3-yl)acetic acid Chemical compound N=1SC(NC=O)=NC=1C(C(=O)O)=NOC1CCCC1 FYCAOIPIRIEEGB-UHFFFAOYSA-N 0.000 description 1
JCJODSMQBXMELN-UHFFFAOYSA-N 2-ethyl-5-phenyl-1,2-oxazol-2-ium Chemical compound O1[N+](CC)=CC=C1C1=CC=CC=C1 JCJODSMQBXMELN-UHFFFAOYSA-N 0.000 description 1
LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 description 1
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
NCLIGEZQAPUUQU-UHFFFAOYSA-N 2-silylacetamide Chemical compound NC(=O)C[SiH3] NCLIGEZQAPUUQU-UHFFFAOYSA-N 0.000 description 1
RGUABPVONIGVAT-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)propan-1-amine Chemical compound CN1CCN(CCCN)CC1 RGUABPVONIGVAT-UHFFFAOYSA-N 0.000 description 1
NSGUSFGRUOCMNY-UHFFFAOYSA-N 3-[[(5-amino-1,2,4-thiadiazol-3-yl)-carboxymethylidene]amino]oxybenzoic acid Chemical compound S1C(N)=NC(C(=NOC=2C=C(C=CC=2)C(O)=O)C(O)=O)=N1 NSGUSFGRUOCMNY-UHFFFAOYSA-N 0.000 description 1
AJKDUJRRWLQXHM-UHFFFAOYSA-N 3-bromocyclohexene Chemical compound BrC1CCCC=C1 AJKDUJRRWLQXHM-UHFFFAOYSA-N 0.000 description 1
125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
VJHTZTZXOKVQRN-MICDWDOJSA-N 3-deuterio-1,2,4-thiadiazol-5-amine Chemical compound [2H]C1=NSC(N)=N1 VJHTZTZXOKVQRN-MICDWDOJSA-N 0.000 description 1
UIKUBYKUYUSRSM-UHFFFAOYSA-N 3-morpholinopropylamine Chemical compound NCCCN1CCOCC1 UIKUBYKUYUSRSM-UHFFFAOYSA-N 0.000 description 1
CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 1
MODAULMVTKWLKJ-UHFFFAOYSA-N 5-amino-1,2,4-thiadiazol-3-one Chemical compound NC1=NC(=O)NS1 MODAULMVTKWLKJ-UHFFFAOYSA-N 0.000 description 1
FGLWYEULLSTVMA-UHFFFAOYSA-N 5-methyl-3h-1,3,4-thiadiazol-2-one Chemical compound CC1=NN=C(O)S1 FGLWYEULLSTVMA-UHFFFAOYSA-N 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
229910000497 Amalgam Inorganic materials 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
JFIRAVRDSPYUOF-IWSPRGBSSA-N C(C)(C)(C)OC(=O)CON=C(C(=O)NC1[C@@H]2N(C(=C(CS2)Cl)C(=O)O)C1=O)C1=NSC(=N1)N Chemical compound C(C)(C)(C)OC(=O)CON=C(C(=O)NC1[C@@H]2N(C(=C(CS2)Cl)C(=O)O)C1=O)C1=NSC(=N1)N JFIRAVRDSPYUOF-IWSPRGBSSA-N 0.000 description 1
CFYVQDRTUVOCPU-MNWKQKBLSA-N CC1C=C(N2[C@H](S1)C(C2=O)NC(=O)C(=NOCC(=O)OC(C)(C)C)C3=NSC(=N3)N)C(=O)O Chemical compound CC1C=C(N2[C@H](S1)C(C2=O)NC(=O)C(=NOCC(=O)OC(C)(C)C)C3=NSC(=N3)N)C(=O)O CFYVQDRTUVOCPU-MNWKQKBLSA-N 0.000 description 1
MONDNNJXGQHKBD-UHFFFAOYSA-N C[S+]=C(C(C1=NSC(NC=O)=N1)=O)[O-] Chemical compound C[S+]=C(C(C1=NSC(NC=O)=N1)=O)[O-] MONDNNJXGQHKBD-UHFFFAOYSA-N 0.000 description 1
229910021555 Chromium Chloride Inorganic materials 0.000 description 1
208000035473 Communicable disease Diseases 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
FVIGODVHAVLZOO-UHFFFAOYSA-N Dixanthogen Chemical compound CCOC(=S)SSC(=S)OCC FVIGODVHAVLZOO-UHFFFAOYSA-N 0.000 description 1
241000192125 Firmicutes Species 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
241000588748 Klebsiella Species 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
KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
MPCRDALPQLDDFX-UHFFFAOYSA-L Magnesium perchlorate Chemical compound [Mg+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O MPCRDALPQLDDFX-UHFFFAOYSA-L 0.000 description 1
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
241000588767 Proteus vulgaris Species 0.000 description 1
241000589516 Pseudomonas Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
229920006172 Tetrafluoroethylene propylene Polymers 0.000 description 1
241001122767 Theaceae Species 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 1
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
102000001400 Tryptase Human genes 0.000 description 1
108060005989 Tryptase Proteins 0.000 description 1
NERPUFSBOPVLBD-UHFFFAOYSA-M [Br-].C(C)OC(=O)C1=C(C=CC=C1)[I+]C1=CC=CC=C1 Chemical compound [Br-].C(C)OC(=O)C1=C(C=CC=C1)[I+]C1=CC=CC=C1 NERPUFSBOPVLBD-UHFFFAOYSA-M 0.000 description 1
VCLUPMXBNPZJCW-UHFFFAOYSA-M [Cl-].FC(F)(F)C1=C(C=CC=C1)[I+]C1=CC=CC=C1 Chemical compound [Cl-].FC(F)(F)C1=C(C=CC=C1)[I+]C1=CC=CC=C1 VCLUPMXBNPZJCW-UHFFFAOYSA-M 0.000 description 1
150000001243 acetic acids Chemical class 0.000 description 1
VXCTZOGBAFBGAZ-HNXVESTDSA-N acetyloxymethyl (6R)-7-[[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-cyclopentyloxyiminoacetyl]amino]-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1(CCCC1)ON=C(C(=O)NC1[C@@H]2N(C(=CC(S2)C)C(=O)OCOC(C)=O)C1=O)C1=NSC(=N1)N VXCTZOGBAFBGAZ-HNXVESTDSA-N 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000008186 active pharmaceutical agent Substances 0.000 description 1
125000005042 acyloxymethyl group Chemical group 0.000 description 1
239000008272 agar Substances 0.000 description 1
238000002814 agar dilution Methods 0.000 description 1
150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
229910000316 alkaline earth metal phosphate Inorganic materials 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
125000001118 alkylidene group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
125000006242 amine protecting group Chemical group 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 1
KZOWNALBTMILAP-JBMRGDGGSA-N ancitabine hydrochloride Chemical compound Cl.N=C1C=CN2[C@@H]3O[C@H](CO)[C@@H](O)[C@@H]3OC2=N1 KZOWNALBTMILAP-JBMRGDGGSA-N 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
235000009697 arginine Nutrition 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
244000052616 bacterial pathogen Species 0.000 description 1
UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical class C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
ILEVVWHGYIIWGR-UHFFFAOYSA-N benzyl 2-(1,3-dioxoisoindol-2-yl)oxypropanoate Chemical compound O=C1C2=CC=CC=C2C(=O)N1OC(C)C(=O)OCC1=CC=CC=C1 ILEVVWHGYIIWGR-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
SZOHSFVTEGLKML-UHFFFAOYSA-M bis(4-fluorophenyl)iodanium;chloride Chemical compound [Cl-].C1=CC(F)=CC=C1[I+]C1=CC=C(F)C=C1 SZOHSFVTEGLKML-UHFFFAOYSA-M 0.000 description 1
SIOVKLKJSOKLIF-UHFFFAOYSA-N bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)OC(C)=N[Si](C)(C)C SIOVKLKJSOKLIF-UHFFFAOYSA-N 0.000 description 1
LOXORFRCPXUORP-UHFFFAOYSA-N bromo-Cycloheptane Chemical compound BrC1CCCCCC1 LOXORFRCPXUORP-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
XDKIPZSDYIMGOO-UHFFFAOYSA-N butyl 2-(1,3-dioxoisoindol-2-yl)oxypropanoate Chemical compound C1=CC=C2C(=O)N(OC(C)C(=O)OCCCC)C(=O)C2=C1 XDKIPZSDYIMGOO-UHFFFAOYSA-N 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical compound NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 1
150000001721 carbon Chemical class 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000010531 catalytic reduction reaction Methods 0.000 description 1
YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000012069 chiral reagent Substances 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
QQVDYSUDFZZPSU-UHFFFAOYSA-M chloromethylidene(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CCl QQVDYSUDFZZPSU-UHFFFAOYSA-M 0.000 description 1
150000001845 chromium compounds Chemical class 0.000 description 1
QSWDMMVNRMROPK-UHFFFAOYSA-K chromium(3+) trichloride Chemical compound [Cl-].[Cl-].[Cl-].[Cr+3] QSWDMMVNRMROPK-UHFFFAOYSA-K 0.000 description 1
WYYQVWLEPYFFLP-UHFFFAOYSA-K chromium(3+);triacetate Chemical compound [Cr+3].CC([O-])=O.CC([O-])=O.CC([O-])=O WYYQVWLEPYFFLP-UHFFFAOYSA-K 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
JONGUYRYOWEYAS-UHFFFAOYSA-N cyclohexyl 2-(1,3-dioxoisoindol-2-yl)oxypropanoate Chemical compound O=C1C2=CC=CC=C2C(=O)N1OC(C)C(=O)OC1CCCCC1 JONGUYRYOWEYAS-UHFFFAOYSA-N 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
FBCCMZVIWNDFMO-UHFFFAOYSA-N dichloroacetyl chloride Chemical compound ClC(Cl)C(Cl)=O FBCCMZVIWNDFMO-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
AXZAYXJCENRGIM-UHFFFAOYSA-J dipotassium;tetrabromoplatinum(2-) Chemical compound [K+].[K+].[Br-].[Br-].[Br-].[Br-].[Pt+2] AXZAYXJCENRGIM-UHFFFAOYSA-J 0.000 description 1
BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000012990 dithiocarbamate Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
210000000981 epithelium Anatomy 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
MAUKRAODYPUHJG-UHFFFAOYSA-N ethyl 2-(1,3-dioxoisoindol-2-yl)oxyacetate Chemical compound C1=CC=C2C(=O)N(OCC(=O)OCC)C(=O)C2=C1 MAUKRAODYPUHJG-UHFFFAOYSA-N 0.000 description 1
YJSIYYFSBCZIMG-UHFFFAOYSA-N ethyl 2-amino-2-oxoacetate;hydrochloride Chemical compound Cl.CCOC(=O)C(N)=O YJSIYYFSBCZIMG-UHFFFAOYSA-N 0.000 description 1
VNUUSOJDAJMVLQ-UHFFFAOYSA-N ethyl 2-aminooxyacetate Chemical compound CCOC(=O)CON VNUUSOJDAJMVLQ-UHFFFAOYSA-N 0.000 description 1
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
WMYNMYVRWWCRPS-UHFFFAOYSA-N ethynoxyethane Chemical group CCOC#C WMYNMYVRWWCRPS-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000004993 haloalkoxycarbonyl group Chemical group 0.000 description 1
230000002140 halogenating effect Effects 0.000 description 1
229910001385 heavy metal Inorganic materials 0.000 description 1
JYVHOGDBFNJNMR-UHFFFAOYSA-N hexane;hydrate Chemical compound O.CCCCCC JYVHOGDBFNJNMR-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
229910000041 hydrogen chloride Inorganic materials 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
XIQUJVRFXPBMHS-UHFFFAOYSA-N hydron;o-prop-2-enylhydroxylamine;chloride Chemical compound Cl.NOCC=C XIQUJVRFXPBMHS-UHFFFAOYSA-N 0.000 description 1
150000004679 hydroxides Chemical class 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
238000011534 incubation Methods 0.000 description 1
229910003480 inorganic solid Inorganic materials 0.000 description 1
CBEQRNSPHCCXSH-UHFFFAOYSA-N iodine monobromide Chemical compound IBr CBEQRNSPHCCXSH-UHFFFAOYSA-N 0.000 description 1
PELJISAVHGXLAL-UHFFFAOYSA-N iodomethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCI PELJISAVHGXLAL-UHFFFAOYSA-N 0.000 description 1
VFQXVTODMYMSMJ-UHFFFAOYSA-N isonicotinamide Chemical compound NC(=O)C1=CC=NC=C1 VFQXVTODMYMSMJ-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000004750 isotope dilution mass spectroscopy Methods 0.000 description 1
229960003881 letrozole Drugs 0.000 description 1
YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
PZLXYMQOCNYUIO-UHFFFAOYSA-N lithium;hydrochloride Chemical compound [Li].Cl PZLXYMQOCNYUIO-UHFFFAOYSA-N 0.000 description 1
235000018977 lysine Nutrition 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
239000000347 magnesium hydroxide Substances 0.000 description 1
229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
239000004137 magnesium phosphate Substances 0.000 description 1
229910000157 magnesium phosphate Inorganic materials 0.000 description 1
229960002261 magnesium phosphate Drugs 0.000 description 1
235000010994 magnesium phosphates Nutrition 0.000 description 1
229910000000 metal hydroxide Inorganic materials 0.000 description 1
150000004692 metal hydroxides Chemical class 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
XMYQHJDBLRZMLW-UHFFFAOYSA-N methanolamine Chemical compound NCO XMYQHJDBLRZMLW-UHFFFAOYSA-N 0.000 description 1
HQOQSFITXGQQDM-SSDOTTSWSA-N methyl (6R)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound COC(=O)C1=CCS[C@@H]2CC(=O)N12 HQOQSFITXGQQDM-SSDOTTSWSA-N 0.000 description 1
HBRBUDPMESALKK-UHFFFAOYSA-N methyl 2-amino-2-iminoacetate;hydrobromide Chemical compound Br.COC(=O)C(N)=N HBRBUDPMESALKK-UHFFFAOYSA-N 0.000 description 1
229940050176 methyl chloride Drugs 0.000 description 1
OLXYLDUSSBULGU-UHFFFAOYSA-N methyl pyridine-4-carboxylate Chemical compound COC(=O)C1=CC=NC=C1 OLXYLDUSSBULGU-UHFFFAOYSA-N 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
230000000813 microbial effect Effects 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000002156 mixing Methods 0.000 description 1
XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 1
SJXULIRYGQTEJK-UHFFFAOYSA-N n'-(2-morpholin-4-ylethyl)methanediimine Chemical compound N=C=NCCN1CCOCC1 SJXULIRYGQTEJK-UHFFFAOYSA-N 0.000 description 1
JEUXZUSUYIHGNL-UHFFFAOYSA-N n,n-diethylethanamine;hydrate Chemical compound O.CCN(CC)CC JEUXZUSUYIHGNL-UHFFFAOYSA-N 0.000 description 1
YFZBPSXRYCOKCW-UHFFFAOYSA-N n-(3-aminopropyl)acetamide Chemical compound CC(=O)NCCCN YFZBPSXRYCOKCW-UHFFFAOYSA-N 0.000 description 1
MWYJQJGYPCJCOI-UHFFFAOYSA-N n-[3-(2-methylsulfanyl-2-methylsulfinylacetyl)-1,2,4-thiadiazol-5-yl]formamide Chemical compound CSC(S(C)=O)C(=O)C1=NSC(NC=O)=N1 MWYJQJGYPCJCOI-UHFFFAOYSA-N 0.000 description 1
YHKYKATVKVZYHW-UHFFFAOYSA-N n-[4-(5-sulfanylidene-2h-tetrazol-1-yl)butyl]acetamide Chemical compound CC(=O)NCCCCN1N=NNC1=S YHKYKATVKVZYHW-UHFFFAOYSA-N 0.000 description 1
RPXRJKHNFVWZDU-UHFFFAOYSA-N n-[6-(5-sulfanylidene-2h-tetrazol-1-yl)hexyl]acetamide Chemical compound CC(=O)NCCCCCCN1N=NN=C1S RPXRJKHNFVWZDU-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
KPADFPAILITQBG-UHFFFAOYSA-N non-4-ene Chemical compound CCCCC=CCCC KPADFPAILITQBG-UHFFFAOYSA-N 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
FMJIREFIIGRAAJ-UHFFFAOYSA-N o-(1-phenylethyl)hydroxylamine Chemical compound NOC(C)C1=CC=CC=C1 FMJIREFIIGRAAJ-UHFFFAOYSA-N 0.000 description 1
LZHLKGAMXQASQE-UHFFFAOYSA-N o-(2,2,2-trifluoroethyl)hydroxylamine Chemical compound NOCC(F)(F)F LZHLKGAMXQASQE-UHFFFAOYSA-N 0.000 description 1
HUFRFGUWEJJANL-UHFFFAOYSA-N o-cycloheptylhydroxylamine Chemical compound NOC1CCCCCC1 HUFRFGUWEJJANL-UHFFFAOYSA-N 0.000 description 1
LDRDISULAKPGRY-UHFFFAOYSA-N o-cyclohex-2-en-1-ylhydroxylamine Chemical compound NOC1CCCC=C1 LDRDISULAKPGRY-UHFFFAOYSA-N 0.000 description 1
HWWCBAWGNJYHPP-UHFFFAOYSA-N o-cyclopentylhydroxylamine Chemical compound NOC1CCCC1 HWWCBAWGNJYHPP-UHFFFAOYSA-N 0.000 description 1
239000002674 ointment Substances 0.000 description 1
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-M perchlorate Inorganic materials [O-]Cl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-M 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000008055 phosphate buffer solution Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
JLKDVMWYMMLWTI-UHFFFAOYSA-M potassium iodate Chemical compound [K+].[O-]I(=O)=O JLKDVMWYMMLWTI-UHFFFAOYSA-M 0.000 description 1
239000001230 potassium iodate Substances 0.000 description 1
235000006666 potassium iodate Nutrition 0.000 description 1
229940093930 potassium iodate Drugs 0.000 description 1
229910001487 potassium perchlorate Inorganic materials 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
229940007042 proteus vulgaris Drugs 0.000 description 1
238000000746 purification Methods 0.000 description 1
229960002026 pyrithione Drugs 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
238000006894 reductive elimination reaction Methods 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
229910001488 sodium perchlorate Inorganic materials 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
MITYJMQACATQLP-UHFFFAOYSA-N tert-butyl 2-(1,3-dioxoisoindol-2-yl)oxy-2-methylpropanoate Chemical compound C1=CC=C2C(=O)N(OC(C)(C)C(=O)OC(C)(C)C)C(=O)C2=C1 MITYJMQACATQLP-UHFFFAOYSA-N 0.000 description 1
WHIGPILZMGCQKN-UHFFFAOYSA-N tert-butyl 2-(1,3-dioxoisoindol-2-yl)oxy-2-phenylacetate Chemical compound O=C1C2=CC=CC=C2C(=O)N1OC(C(=O)OC(C)(C)C)C1=CC=CC=C1 WHIGPILZMGCQKN-UHFFFAOYSA-N 0.000 description 1
JSUWPTFAHGCIFF-UHFFFAOYSA-N tert-butyl 2-(1,3-dioxoisoindol-2-yl)oxy-3-methylbutanoate Chemical compound C1=CC=C2C(=O)N(OC(C(C)C)C(=O)OC(C)(C)C)C(=O)C2=C1 JSUWPTFAHGCIFF-UHFFFAOYSA-N 0.000 description 1
APBDROVGLRLEDJ-UHFFFAOYSA-N tert-butyl 2-(1,3-dioxoisoindol-2-yl)oxypropanoate Chemical compound C1=CC=C2C(=O)N(OC(C)C(=O)OC(C)(C)C)C(=O)C2=C1 APBDROVGLRLEDJ-UHFFFAOYSA-N 0.000 description 1
ZPIHBLASZNAFMU-UHFFFAOYSA-N tert-butyl 2-aminooxy-2-phenylacetate Chemical compound CC(C)(C)OC(=O)C(ON)C1=CC=CC=C1 ZPIHBLASZNAFMU-UHFFFAOYSA-N 0.000 description 1
SUNJKJWWNNMWSL-UHFFFAOYSA-N tert-butyl 2-aminooxy-3-methylbutanoate Chemical compound CC(C)C(ON)C(=O)OC(C)(C)C SUNJKJWWNNMWSL-UHFFFAOYSA-N 0.000 description 1
QQWYQAQQADNEIC-UHFFFAOYSA-N tert-butyl [[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)ON=C(C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-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
NDEXIGADWLWQQT-UHFFFAOYSA-N tert-butyl n-[3-(5-sulfanylidene-2h-tetrazol-1-yl)propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCN1N=NN=C1S NDEXIGADWLWQQT-UHFFFAOYSA-N 0.000 description 1
HEMAFPORRHPVGN-UHFFFAOYSA-N tert-butyl n-[4-(5-sulfanylidene-2h-tetrazol-1-yl)butyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCCN1NN=NC1=S HEMAFPORRHPVGN-UHFFFAOYSA-N 0.000 description 1
JTXGWNNMDFFVCZ-UHFFFAOYSA-N tert-butyl n-[6-(5-sulfanylidene-2h-tetrazol-1-yl)hexyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCCCCN1NN=NC1=S JTXGWNNMDFFVCZ-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
125000005934 tert-pentyloxycarbonyl group Chemical group 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 description 1
LWFUGGGWLUMXQZ-UHFFFAOYSA-N tetrazolo[1,5-b]pyridazine Chemical compound C1=CC=NN2N=NN=C21 LWFUGGGWLUMXQZ-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
QHUNJMXHQHHWQP-UHFFFAOYSA-N trimethylsilyl acetate Chemical compound CC(=O)O[Si](C)(C)C QHUNJMXHQHHWQP-UHFFFAOYSA-N 0.000 description 1
JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 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
229920001567 vinyl ester resin Polymers 0.000 description 1
NLVXSWCKKBEXTG-UHFFFAOYSA-N vinylsulfonic acid Chemical compound OS(=O)(=O)C=C NLVXSWCKKBEXTG-UHFFFAOYSA-N 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1