IL124337A

IL124337A - Pyrido-oxazine derivatives, pharmaceutical preparations containing them and a method for their preparation

Pyrido-oxazine derivatives, pharmaceutical preparations containing them and a method for their preparation

Info

Publication number: IL124337A
Authority: IL; Israel
Prior art keywords: dihydro; compound; yield; found; calc
Prior art date: 1995-11-07

Application number

IL12433796A

Other languages

English (en)

Hebrew (he)

Other versions

IL124337A0 (en

Original Assignee

Ortho Mcneil Pharm Inc

Priority date

1995-11-07

Filing date

1996-10-17

Publication date

2001-08-08

1996-10-17 Application filed by Ortho Mcneil Pharm Inc filed Critical Ortho Mcneil Pharm Inc

1998-12-06 Publication of IL124337A0 publication Critical patent/IL124337A0/xx

2001-08-08 Publication of IL124337A publication Critical patent/IL124337A/en

Links

238000000034 method Methods 0.000 title claims abstract description 260
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
SHASOVNNKCSWPT-UHFFFAOYSA-N 2h-pyrido[2,3-e]oxazine Chemical class C1=CN=C2C=CNOC2=C1 SHASOVNNKCSWPT-UHFFFAOYSA-N 0.000 title abstract description 7
238000004519 manufacturing process Methods 0.000 title abstract description 7
150000001875 compounds Chemical class 0.000 claims abstract description 129
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
125000004076 pyridyl group Chemical group 0.000 claims abstract description 6
CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 claims abstract description 5
208000035143 Bacterial infection Diseases 0.000 claims abstract description 4
208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 85
229910052739 hydrogen Inorganic materials 0.000 claims description 41
-1 daim compound Chemical class 0.000 claims description 38
239000001257 hydrogen Substances 0.000 claims description 26
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
229910052757 nitrogen Inorganic materials 0.000 claims description 14
239000002904 solvent Substances 0.000 claims description 14
150000002148 esters Chemical class 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
125000006239 protecting group Chemical group 0.000 claims description 5
229920006395 saturated elastomer Polymers 0.000 claims description 5
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 4
125000000217 alkyl group Chemical group 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000000623 heterocyclic group Chemical group 0.000 claims description 3
229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 7
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
239000011593 sulfur Substances 0.000 claims 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
125000004744 butyloxycarbonyl group Chemical group 0.000 claims 1
125000001624 naphthyl group Chemical group 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims 1
230000000844 anti-bacterial effect Effects 0.000 abstract description 5
238000005481 NMR spectroscopy Methods 0.000 description 103
239000007787 solid Substances 0.000 description 98
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 84
238000005160 1H NMR spectroscopy Methods 0.000 description 81
229910001868 water Inorganic materials 0.000 description 77
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 74
239000000047 product Substances 0.000 description 62
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
230000002152 alkylating effect Effects 0.000 description 44
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
235000019439 ethyl acetate Nutrition 0.000 description 30
238000006243 chemical reaction Methods 0.000 description 28
239000000243 solution Substances 0.000 description 28
239000000843 powder Substances 0.000 description 26
QRAOZQGIUIDZQZ-UHFFFAOYSA-N 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1,4-benzoxazine Chemical compound C=1C=C2N(C)CCOC2=CC=1B1OC(C)(C)C(C)(C)O1 QRAOZQGIUIDZQZ-UHFFFAOYSA-N 0.000 description 25
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
238000003818 flash chromatography Methods 0.000 description 22
239000006260 foam Substances 0.000 description 22
108090000623 proteins and genes Proteins 0.000 description 21
239000003153 chemical reaction reagent Substances 0.000 description 20
238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 20
241000894006 Bacteria Species 0.000 description 18
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 18
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 18
101150046236 CNR1 gene Proteins 0.000 description 17
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 17
RRBQFCSWRFOXQO-UHFFFAOYSA-N CCCCOC(=O)NC(=N)N(C(=O)OCCCC)CCC1=CC=C(O)C=C1 Chemical compound CCCCOC(=O)NC(=N)N(C(=O)OCCCC)CCC1=CC=C(O)C=C1 RRBQFCSWRFOXQO-UHFFFAOYSA-N 0.000 description 16
108010072039 Histidine kinase Proteins 0.000 description 16
238000005859 coupling reaction Methods 0.000 description 16
238000002425 crystallisation Methods 0.000 description 16
230000008025 crystallization Effects 0.000 description 16
239000000203 mixture Substances 0.000 description 16
HRRLOYAIEBAUHR-UHFFFAOYSA-N 2-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(=O)C(CCO[Si](C)(C)C(C)(C)C)OC2=C1 HRRLOYAIEBAUHR-UHFFFAOYSA-N 0.000 description 15
239000003921 oil Substances 0.000 description 15
235000019198 oils Nutrition 0.000 description 15
LZIYAIRGDHSVED-UHFFFAOYSA-N 1-(bromomethyl)-3-chlorobenzene Chemical compound ClC1=CC=CC(CBr)=C1 LZIYAIRGDHSVED-UHFFFAOYSA-N 0.000 description 14
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
239000012043 crude product Substances 0.000 description 14
102000004169 proteins and genes Human genes 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
230000008878 coupling Effects 0.000 description 13
238000010168 coupling process Methods 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 12
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
239000000463 material Substances 0.000 description 11
238000001665 trituration Methods 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
238000003756 stirring Methods 0.000 description 10
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 10
229910019142 PO4 Inorganic materials 0.000 description 9
230000001580 bacterial effect Effects 0.000 description 9
239000003814 drug Substances 0.000 description 9
230000000694 effects Effects 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
230000004048 modification Effects 0.000 description 9
238000012986 modification Methods 0.000 description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 9
239000010452 phosphate Substances 0.000 description 9
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 9
238000000746 purification Methods 0.000 description 9
238000012360 testing method Methods 0.000 description 9
108091000080 Phosphotransferase Proteins 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
229910052736 halogen Inorganic materials 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
102000020233 phosphotransferase Human genes 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
150000003839 salts Chemical class 0.000 description 8
239000002253 acid Substances 0.000 description 7
239000003242 anti bacterial agent Substances 0.000 description 7
239000000499 gel Substances 0.000 description 7
150000002367 halogens Chemical class 0.000 description 7
150000002431 hydrogen Chemical class 0.000 description 7
239000007788 liquid Substances 0.000 description 7
239000000155 melt Substances 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
230000009467 reduction Effects 0.000 description 7
238000006722 reduction reaction Methods 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
239000000370 acceptor Substances 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
238000003556 assay Methods 0.000 description 6
230000035578 autophosphorylation Effects 0.000 description 6
239000002585 base Substances 0.000 description 6
150000005323 carbonate salts Chemical class 0.000 description 6
239000012230 colorless oil Substances 0.000 description 6
229940079593 drug Drugs 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
230000014509 gene expression Effects 0.000 description 6
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 6
OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 6
239000007858 starting material Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 6
238000006751 Mitsunobu reaction Methods 0.000 description 5
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 5
229940088710 antibiotic agent Drugs 0.000 description 5
230000033228 biological regulation Effects 0.000 description 5
239000012267 brine Substances 0.000 description 5
238000004440 column chromatography Methods 0.000 description 5
239000013058 crude material Substances 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
230000007246 mechanism Effects 0.000 description 5
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
239000002243 precursor Substances 0.000 description 5
230000008569 process Effects 0.000 description 5
230000004044 response Effects 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
APGGSERFJKEWFG-UHFFFAOYSA-N 1-(chloromethyl)-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(CCl)=C1 APGGSERFJKEWFG-UHFFFAOYSA-N 0.000 description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
241000975394 Evechinus chloroticus Species 0.000 description 4
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
241000191967 Staphylococcus aureus Species 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
235000011114 ammonium hydroxide Nutrition 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
238000010511 deprotection reaction Methods 0.000 description 4
238000001514 detection method Methods 0.000 description 4
NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000003112 inhibitor Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
235000015320 potassium carbonate Nutrition 0.000 description 4
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
238000010992 reflux Methods 0.000 description 4
230000001105 regulatory effect Effects 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
238000012546 transfer Methods 0.000 description 4
230000009466 transformation Effects 0.000 description 4
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
BXCBUWKTXLWPSB-UHFFFAOYSA-N 1-(chloromethyl)-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1CCl BXCBUWKTXLWPSB-UHFFFAOYSA-N 0.000 description 3
HLQZCRVEEQKNMS-UHFFFAOYSA-N 1-(chloromethyl)-4-phenylbenzene Chemical compound C1=CC(CCl)=CC=C1C1=CC=CC=C1 HLQZCRVEEQKNMS-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
230000007940 bacterial gene expression Effects 0.000 description 3
150000005130 benzoxazines Chemical class 0.000 description 3
GZWGRGWVLLDFLG-UHFFFAOYSA-N butyl n-[2-(4-hydroxyphenyl)ethyl]carbamate Chemical compound CCCCOC(=O)NCCC1=CC=C(O)C=C1 GZWGRGWVLLDFLG-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
229940125782 compound 2 Drugs 0.000 description 3
239000006185 dispersion Substances 0.000 description 3
BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 3
239000011521 glass Substances 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
125000004356 hydroxy functional group Chemical group O* 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
229940095102 methyl benzoate Drugs 0.000 description 3
244000005700 microbiome Species 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
150000002989 phenols Chemical class 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 3
241000894007 species Species 0.000 description 3
230000004083 survival effect Effects 0.000 description 3
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238000013518 transcription Methods 0.000 description 3
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238000000844 transformation Methods 0.000 description 3
229910052721 tungsten Inorganic materials 0.000 description 3
230000001018 virulence Effects 0.000 description 3
ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 2
GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 2
VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 2
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