OA12779A - N-aryl-2-oxazolidinone-5-carboxamides and their derivates and their use as antibacterials. - Google Patents

Info

Publication number

OA12779A

OA12779A OA1200400221A OA1200400221A OA12779A OA 12779 A OA12779 A OA 12779A OA 1200400221 A OA1200400221 A OA 1200400221A OA 1200400221 A OA1200400221 A OA 1200400221A OA 12779 A OA12779 A OA 12779A

Authority

OA

OAPI

Prior art keywords

oxo

oxazolidinecarboxamide

alkyl

dihydro

methyl

Prior art date

2002-02-25

Links

• Espacenet
• Global Dossier
• Discuss

• 230000000844 anti-bacterial effect Effects 0.000 title description 5
• 229940088710 antibiotic agent Drugs 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 349
• 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 14
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 210
• 125000000217 alkyl group Chemical group 0.000 claims description 195
• -1 phenyl,benzyl Chemical group 0.000 claims description 152
• 229910052739 hydrogen Inorganic materials 0.000 claims description 94
• 125000005843 halogen group Chemical group 0.000 claims description 87
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
• 125000003118 aryl group Chemical group 0.000 claims description 59
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 53
• 125000003545 alkoxy group Chemical group 0.000 claims description 51
• 229910052757 nitrogen Inorganic materials 0.000 claims description 41
• 238000011282 treatment Methods 0.000 claims description 38
• 229910052717 sulfur Inorganic materials 0.000 claims description 36
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 29
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 29
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
• 125000001424 substituent group Chemical group 0.000 claims description 25
• 125000003342 alkenyl group Chemical group 0.000 claims description 24
• RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 23
• FTAPDLRVRYASRX-UHFFFAOYSA-N 1,3-oxazolidine-2-carboxamide Chemical compound NC(=O)C1NCCO1 FTAPDLRVRYASRX-UHFFFAOYSA-N 0.000 claims description 22
• 125000002252 acyl group Chemical group 0.000 claims description 22
• 229910052760 oxygen Inorganic materials 0.000 claims description 22
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 22
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 21
• 229920006395 saturated elastomer Polymers 0.000 claims description 20
• 125000000623 heterocyclic group Chemical group 0.000 claims description 19
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 17
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• 125000004432 carbon atom Chemical group C* 0.000 claims description 16
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
• 125000004429 atom Chemical group 0.000 claims description 12
• 229910052731 fluorine Inorganic materials 0.000 claims description 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• 229910052801 chlorine Inorganic materials 0.000 claims description 11
• 229910052794 bromium Inorganic materials 0.000 claims description 10
• 125000005842 heteroatom Chemical group 0.000 claims description 10
• 239000011734 sodium Substances 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 9
• 208000015181 infectious disease Diseases 0.000 claims description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
• 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 claims description 8
• 125000004193 piperazinyl group Chemical group 0.000 claims description 8
• 229910052708 sodium Inorganic materials 0.000 claims description 8
• 125000005942 tetrahydropyridyl group Chemical group 0.000 claims description 8
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
• 125000004414 alkyl thio group Chemical group 0.000 claims description 7
• 125000002393 azetidinyl group Chemical group 0.000 claims description 7
• 230000000813 microbial effect Effects 0.000 claims description 7
• JCSCLHOUNBXMEE-CYBMUJFWSA-N (5r)-3-[4-(3,6-dihydro-2h-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC=C1C1=CCSCC1 JCSCLHOUNBXMEE-CYBMUJFWSA-N 0.000 claims description 6
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 6
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 6
• 229910052744 lithium Inorganic materials 0.000 claims description 6
• 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 claims description 6
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 5
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 5
• 230000037396 body weight Effects 0.000 claims description 5
• 125000002950 monocyclic group Chemical group 0.000 claims description 5
• 239000011591 potassium Substances 0.000 claims description 5
• 229910052700 potassium Inorganic materials 0.000 claims description 5
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 5
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 5
• 125000004434 sulfur atom Chemical group 0.000 claims description 5
• BKSSCIZNJVZMEX-LLVKDONJSA-N (5r)-2-oxo-3-(2-oxo-3-propan-2-yl-1,3-benzoxazol-6-yl)-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2OC(=O)N(C(C)C)C2=CC=C1N1C[C@H](C(N)=O)OC1=O BKSSCIZNJVZMEX-LLVKDONJSA-N 0.000 claims description 4
• ZTAAKFXBCMVLOG-LLVKDONJSA-N (5r)-3-(3,5-difluoro-4-thiomorpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC(F)=C1N1CCSCC1 ZTAAKFXBCMVLOG-LLVKDONJSA-N 0.000 claims description 4
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 4
• 125000000304 alkynyl group Chemical group 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
• CWTYBIOALFDHGB-SNVBAGLBSA-N (5r)-3-(3-ethyl-2-oxo-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2OC(=O)N(CC)C2=CC=C1N1C[C@H](C(N)=O)OC1=O CWTYBIOALFDHGB-SNVBAGLBSA-N 0.000 claims description 3
• NUZHYTLBLZEQNG-MRVPVSSYSA-N (5r)-3-(4-fluoro-3-methyl-2-oxo-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2OC(=O)N(C)C2=C(F)C=C1N1C[C@H](C(N)=O)OC1=O NUZHYTLBLZEQNG-MRVPVSSYSA-N 0.000 claims description 3
• PJEOEJUBMVOCCF-LLVKDONJSA-N (5r)-3-[3,5-difluoro-4-(1-imino-1-oxo-1,4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC(F)=C1N1CCS(=N)(=O)CC1 PJEOEJUBMVOCCF-LLVKDONJSA-N 0.000 claims description 3
• KFWKTPVZIZYTGO-CQSZACIVSA-N (5r)-3-[3-fluoro-4-(thian-4-yl)phenyl]-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C(C=C1F)=CC=C1C1CCSCC1 KFWKTPVZIZYTGO-CQSZACIVSA-N 0.000 claims description 3
• 101000983970 Conus catus Alpha-conotoxin CIB Proteins 0.000 claims description 3
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
• 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 claims description 3
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
• 125000004306 triazinyl group Chemical group 0.000 claims description 3
• DRTVZEUJGKZSRI-LLVKDONJSA-N (5r)-3-(3-ethyl-2-oxo-1,3-benzoxazol-6-yl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2OC(=O)N(CC)C2=CC=C1N1C[C@H](C(=O)NC)OC1=O DRTVZEUJGKZSRI-LLVKDONJSA-N 0.000 claims description 2
• WDFGRFQXNVXCIK-SECBINFHSA-N (5r)-3-(3-ethyl-4-fluoro-2-oxo-1,3-benzothiazol-6-yl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(CC)C2=C(F)C=C1N1C[C@H](C(=O)NC)OC1=O WDFGRFQXNVXCIK-SECBINFHSA-N 0.000 claims description 2
• URCRLDDNCLOAMA-CYBMUJFWSA-N (5r)-3-(3-fluoro-4-morpholin-4-ylphenyl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C(C=C1F)=CC=C1N1CCOCC1 URCRLDDNCLOAMA-CYBMUJFWSA-N 0.000 claims description 2
• IPLJXFWUBZYCKS-CYBMUJFWSA-N (5r)-3-(3-fluoro-4-pyridin-3-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C1=CC=C(C=2C=NC=CC=2)C(F)=C1 IPLJXFWUBZYCKS-CYBMUJFWSA-N 0.000 claims description 2
• FQPPEKCCNRMKBJ-GFCCVEGCSA-N (5r)-3-(3-fluoro-4-thiomorpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC=C1N1CCSCC1 FQPPEKCCNRMKBJ-GFCCVEGCSA-N 0.000 claims description 2
• WAGKFNIYFRFVPU-MRVPVSSYSA-N (5r)-3-(3-methyl-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(C)C2=CC=C1N1C[C@H](C(N)=O)OC1=O WAGKFNIYFRFVPU-MRVPVSSYSA-N 0.000 claims description 2
• GRDXHMKGPWSGPF-SSDOTTSWSA-N (5r)-3-(4-fluoro-3-methyl-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(C)C2=C(F)C=C1N1C[C@H](C(N)=O)OC1=O GRDXHMKGPWSGPF-SSDOTTSWSA-N 0.000 claims description 2
• HNPLAXYMRQAUST-SECBINFHSA-N (5r)-3-(4-fluoro-3-methyl-2-oxo-1,3-benzoxazol-6-yl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC(F)=C(N(C)C(=O)O2)C2=C1 HNPLAXYMRQAUST-SECBINFHSA-N 0.000 claims description 2
• FQJBZAVZDYNYMC-PRHODGIISA-N (5r)-3-[(2r)-1-(2-hydroxyacetyl)-2-methyl-2,3-dihydroindol-5-yl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C([C@H](N(C1=CC=2)C(=O)CO)C)C1=CC=2N1C[C@H](C(N)=O)OC1=O FQJBZAVZDYNYMC-PRHODGIISA-N 0.000 claims description 2
• BFCYCWXUPMUIKV-CYBMUJFWSA-N (5r)-3-[3-fluoro-4-(1-formyl-3-methylazetidin-3-yl)phenyl]-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC=C(C2(C)CN(C2)C=O)C(F)=C1 BFCYCWXUPMUIKV-CYBMUJFWSA-N 0.000 claims description 2
• LOLZBSQOTSFWNZ-CYBMUJFWSA-N (5r)-3-[3-fluoro-4-(1-methylimino-1-oxo-1,4-thiazinan-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1CS(=NC)(=O)CCN1C1=CC=C(N2C(O[C@H](C2)C(N)=O)=O)C=C1F LOLZBSQOTSFWNZ-CYBMUJFWSA-N 0.000 claims description 2
• QDBQEWHDGZHOEJ-SNVBAGLBSA-N (5r)-n-(2-fluoroethyl)-3-(3-methyl-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(C)C2=CC=C1N1C[C@H](C(=O)NCCF)OC1=O QDBQEWHDGZHOEJ-SNVBAGLBSA-N 0.000 claims description 2
• YCRTYFWSLRXJEV-LLVKDONJSA-N (5r)-n-methyl-2-oxo-3-(2-oxo-3-propan-2-yl-1,3-benzothiazol-6-yl)-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC=C(N(C(C)C)C(=O)S2)C2=C1 YCRTYFWSLRXJEV-LLVKDONJSA-N 0.000 claims description 2
• 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
• 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 2
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
• VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical group CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 claims description 2
• 101100440695 Dictyostelium discoideum corB gene Proteins 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 239000011575 calcium Substances 0.000 claims description 2
• 229910052791 calcium Inorganic materials 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
• 150000001768 cations Chemical class 0.000 claims description 2
• 125000001041 indolyl group Chemical group 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• PPHTXSXTXAEQGB-LLVKDONJSA-N methyl 3-[4-[(5r)-5-carbamoyl-2-oxo-1,3-oxazolidin-3-yl]-2,6-difluorophenyl]-3-methylazetidine-1-carboxylate Chemical compound C1N(C(=O)OC)CC1(C)C1=C(F)C=C(N2C(O[C@H](C2)C(N)=O)=O)C=C1F PPHTXSXTXAEQGB-LLVKDONJSA-N 0.000 claims description 2
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 2
• 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 2
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 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 13
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 2
• UWKBPPOUKCZHEF-GFCCVEGCSA-N (5r)-2-oxo-3-(4-thiomorpholin-4-ylphenyl)-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C1=CC=C(N2CCSCC2)C=C1 UWKBPPOUKCZHEF-GFCCVEGCSA-N 0.000 claims 1
• GCXVBAMUDDGHGW-GFCCVEGCSA-N (5r)-3-(3,5-difluoro-4-thiomorpholin-4-ylphenyl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C(C=C1F)=CC(F)=C1N1CCSCC1 GCXVBAMUDDGHGW-GFCCVEGCSA-N 0.000 claims 1
• HUKOONNMVLZCLA-SNVBAGLBSA-N (5r)-3-(3-ethyl-4-fluoro-2-oxo-1,3-benzoxazol-6-yl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2OC(=O)N(CC)C2=C(F)C=C1N1C[C@H](C(=O)NC)OC1=O HUKOONNMVLZCLA-SNVBAGLBSA-N 0.000 claims 1
• KDNJZJMUFCQUDR-GFCCVEGCSA-N (5r)-3-(3-fluoro-4-morpholin-4-ylphenyl)-n-hydroxy-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NO)CN1C(C=C1F)=CC=C1N1CCOCC1 KDNJZJMUFCQUDR-GFCCVEGCSA-N 0.000 claims 1
• QRUFMCZLXWGMSH-SNVBAGLBSA-N (5r)-3-(4-fluoro-2-oxo-3-propan-2-yl-1,3-benzothiazol-6-yl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC(F)=C(N(C(C)C)C(=O)S2)C2=C1 QRUFMCZLXWGMSH-SNVBAGLBSA-N 0.000 claims 1
• IQWGDUWNWKVEEN-SNVBAGLBSA-N (5r)-3-(4-fluoro-2-oxo-3-propan-2-yl-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2OC(=O)N(C(C)C)C2=C(F)C=C1N1C[C@H](C(N)=O)OC1=O IQWGDUWNWKVEEN-SNVBAGLBSA-N 0.000 claims 1
• UKRXPEAVVKZTNL-LLVKDONJSA-N (5r)-3-(4-fluoro-2-oxo-3-propan-2-yl-1,3-benzoxazol-6-yl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC(F)=C(N(C(C)C)C(=O)O2)C2=C1 UKRXPEAVVKZTNL-LLVKDONJSA-N 0.000 claims 1
• KQUOQZMXYWNMKZ-GFCCVEGCSA-N (5r)-3-[3,5-difluoro-4-(thian-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC(F)=C1C1CCSCC1 KQUOQZMXYWNMKZ-GFCCVEGCSA-N 0.000 claims 1
• JYHVUZNBUFYCEK-CYBMUJFWSA-N (5r)-3-[3-fluoro-4-(1-imino-1-oxo-1,4-thiazinan-4-yl)phenyl]-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C(C=C1F)=CC=C1N1CCS(=N)(=O)CC1 JYHVUZNBUFYCEK-CYBMUJFWSA-N 0.000 claims 1
• RYZIGHGVLLKQPY-CYBMUJFWSA-N (5r)-3-[3-fluoro-4-(oxan-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC=C1C1CCOCC1 RYZIGHGVLLKQPY-CYBMUJFWSA-N 0.000 claims 1
• NIWCGQZRUBFWOX-CYBMUJFWSA-N (5r)-3-[4-(3,6-dihydro-2h-pyran-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC=C1C1=CCOCC1 NIWCGQZRUBFWOX-CYBMUJFWSA-N 0.000 claims 1
• QTZDPVIMVDPSEF-GFCCVEGCSA-N (5r)-3-[4-(3,6-dihydro-2h-thiopyran-4-yl)-3,5-difluorophenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC(F)=C1C1=CCSCC1 QTZDPVIMVDPSEF-GFCCVEGCSA-N 0.000 claims 1
• MZSMUCCCNLQYJL-SECBINFHSA-N (5r)-n-methyl-3-(3-methyl-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC=C(N(C)C(=O)S2)C2=C1 MZSMUCCCNLQYJL-SECBINFHSA-N 0.000 claims 1
• YXJLHTGVTPQZOX-SNVBAGLBSA-N (5r)-n-methyl-3-(3-methyl-2-oxo-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC=C(N(C)C(=O)O2)C2=C1 YXJLHTGVTPQZOX-SNVBAGLBSA-N 0.000 claims 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims 1
• 241000080590 Niso Species 0.000 claims 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 1
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
• 239000003242 anti bacterial agent Substances 0.000 abstract description 3
• 125000004122 cyclic group Chemical group 0.000 abstract description 2
• 125000002618 bicyclic heterocycle group Chemical group 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 507
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 309
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 190
• 239000000203 mixture Substances 0.000 description 183
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 179
• 238000000034 method Methods 0.000 description 161
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 155
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 153
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 151
• 239000000243 solution Substances 0.000 description 147
• 235000019439 ethyl acetate Nutrition 0.000 description 135
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 108
• 235000002639 sodium chloride Nutrition 0.000 description 85
• 238000006243 chemical reaction Methods 0.000 description 83
• 239000007787 solid Substances 0.000 description 83
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 80
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
• 239000011780 sodium chloride Substances 0.000 description 75
• 239000011541 reaction mixture Substances 0.000 description 66
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
• 239000002904 solvent Substances 0.000 description 60
• 239000000741 silica gel Substances 0.000 description 57
• 229910002027 silica gel Inorganic materials 0.000 description 57
• 229960001866 silicon dioxide Drugs 0.000 description 57
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 54
• 239000000047 product Substances 0.000 description 49
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 47
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 46
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
• 239000000543 intermediate Substances 0.000 description 42
• 239000000725 suspension Substances 0.000 description 42
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 40
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 40
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 39
• 229940093499 ethyl acetate Drugs 0.000 description 39
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
• 239000012074 organic phase Substances 0.000 description 38
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 33
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
• 229940073584 methylene chloride Drugs 0.000 description 32
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 31
• BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 31
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
• 238000001914 filtration Methods 0.000 description 28
• 239000002253 acid Substances 0.000 description 25
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 24
• 238000000746 purification Methods 0.000 description 23
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• 239000010410 layer Substances 0.000 description 22
• MCVFFRWZNYZUIJ-UHFFFAOYSA-M lithium;trifluoromethanesulfonate Chemical compound [Li+].[O-]S(=O)(=O)C(F)(F)F MCVFFRWZNYZUIJ-UHFFFAOYSA-M 0.000 description 22
• 239000003054 catalyst Substances 0.000 description 20
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 19
• 239000012044 organic layer Substances 0.000 description 19
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 239000003480 eluent Substances 0.000 description 18
• 238000010898 silica gel chromatography Methods 0.000 description 18
• 101150041968 CDC13 gene Proteins 0.000 description 17
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 17
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
• 239000000706 filtrate Substances 0.000 description 17
• 239000003921 oil Substances 0.000 description 17
• 235000019198 oils Nutrition 0.000 description 17
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
• 239000003814 drug Substances 0.000 description 16
• 238000003818 flash chromatography Methods 0.000 description 16
• 239000000651 prodrug Substances 0.000 description 16
• 229940002612 prodrug Drugs 0.000 description 16
• 229940079593 drug Drugs 0.000 description 15
• 239000002244 precipitate Substances 0.000 description 15
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
• 229910021529 ammonia Inorganic materials 0.000 description 14
• DYBINGBQLVCRNI-MRXNPFEDSA-N butyl (5r)-2-oxo-3-(4-thiomorpholin-4-ylphenyl)-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCCCC)CN1C1=CC=C(N2CCSCC2)C=C1 DYBINGBQLVCRNI-MRXNPFEDSA-N 0.000 description 14
• 239000012043 crude product Substances 0.000 description 14
• 239000002002 slurry Substances 0.000 description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 13
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 13
• 239000003795 chemical substances by application Substances 0.000 description 13
• 239000007788 liquid Substances 0.000 description 13
• YKNYRRVISWJDSR-GSVOUGTGSA-N methyl (2r)-oxirane-2-carboxylate Chemical compound COC(=O)[C@H]1CO1 YKNYRRVISWJDSR-GSVOUGTGSA-N 0.000 description 13
• 150000003462 sulfoxides Chemical class 0.000 description 13
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 12
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 12
• 229960001040 ammonium chloride Drugs 0.000 description 12
• 235000019270 ammonium chloride Nutrition 0.000 description 12
• 238000004587 chromatography analysis Methods 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 229960004132 diethyl ether Drugs 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 12
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 11
• 239000008346 aqueous phase Substances 0.000 description 11
• 239000002585 base Substances 0.000 description 11
• 239000002775 capsule Substances 0.000 description 11
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 11
• 238000011176 pooling Methods 0.000 description 11
• 235000017557 sodium bicarbonate Nutrition 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• 238000001665 trituration Methods 0.000 description 11
• 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 10
• 239000000969 carrier Substances 0.000 description 10
• 229910000027 potassium carbonate Inorganic materials 0.000 description 10
• 150000003839 salts Chemical class 0.000 description 10
• JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 10
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 9
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 238000004440 column chromatography Methods 0.000 description 9
• 238000002347 injection Methods 0.000 description 9
• 239000007924 injection Substances 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 238000010992 reflux Methods 0.000 description 9
• 229910052938 sodium sulfate Inorganic materials 0.000 description 9
• 235000011152 sodium sulphate Nutrition 0.000 description 9
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• 150000001414 amino alcohols Chemical class 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• LSTHXEKOIMMYML-GFCCVEGCSA-N butyl (5r)-3-(3-methyl-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCCCC)CN1C1=CC=C(N(C)C(=O)S2)C2=C1 LSTHXEKOIMMYML-GFCCVEGCSA-N 0.000 description 8
• 230000003197 catalytic effect Effects 0.000 description 8
• 239000003153 chemical reaction reagent Substances 0.000 description 8
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
• 239000000843 powder Substances 0.000 description 8
• DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
• 239000000126 substance Substances 0.000 description 8
• KVLWKQGXDGNMQF-UHFFFAOYSA-N 2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound NC(=O)C1CNC(=O)O1 KVLWKQGXDGNMQF-UHFFFAOYSA-N 0.000 description 7
• 108010010803 Gelatin Proteins 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• 239000008273 gelatin Substances 0.000 description 7
• 229920000159 gelatin Polymers 0.000 description 7
• 235000019322 gelatine Nutrition 0.000 description 7
• 235000011852 gelatine desserts Nutrition 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 150000004702 methyl esters Chemical class 0.000 description 7
• 229910000069 nitrogen hydride Inorganic materials 0.000 description 7
• 229920001223 polyethylene glycol Polymers 0.000 description 7
• 239000003826 tablet Substances 0.000 description 7
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 6
• QITPMSSAFSZYOP-UHFFFAOYSA-N 6-nitro-3h-1,3-benzothiazol-2-one Chemical class C1=C([N+]([O-])=O)C=C2SC(O)=NC2=C1 QITPMSSAFSZYOP-UHFFFAOYSA-N 0.000 description 6
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 6
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 6
• 150000007513 acids Chemical class 0.000 description 6
• 235000011114 ammonium hydroxide Nutrition 0.000 description 6
• 238000013461 design Methods 0.000 description 6
• 239000002552 dosage form Substances 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 238000009472 formulation Methods 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• 229910052742 iron Inorganic materials 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 229940093956 potassium carbonate Drugs 0.000 description 6
• 235000011181 potassium carbonates Nutrition 0.000 description 6
• 238000001953 recrystallisation Methods 0.000 description 6
• 239000003381 stabilizer Substances 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• OVRJVKCZJCNSOW-UHFFFAOYSA-N thian-4-one Chemical compound O=C1CCSCC1 OVRJVKCZJCNSOW-UHFFFAOYSA-N 0.000 description 6
• 238000010792 warming Methods 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 5
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 5
• CHKQALUEEULCPZ-UHFFFAOYSA-N amino 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S(=O)(=O)ON)C(C)=C1 CHKQALUEEULCPZ-UHFFFAOYSA-N 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• FUHDWFAJHRGBNM-QGZVFWFLSA-N butyl (5r)-2-oxo-3-[4-(thian-4-yl)phenyl]-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCCCC)CN1C1=CC=C(C2CCSCC2)C=C1 FUHDWFAJHRGBNM-QGZVFWFLSA-N 0.000 description 5
• SPKQRZHKGJHLFW-CYBMUJFWSA-N butyl (5r)-3-(3-ethyl-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCCCC)CN1C1=CC=C(N(CC)C(=O)S2)C2=C1 SPKQRZHKGJHLFW-CYBMUJFWSA-N 0.000 description 5
• 239000006185 dispersion Substances 0.000 description 5
• 239000000796 flavoring agent Substances 0.000 description 5
• 239000000499 gel Substances 0.000 description 5
• 239000008240 homogeneous mixture Substances 0.000 description 5
• 229910052740 iodine Inorganic materials 0.000 description 5
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
• 239000008101 lactose Substances 0.000 description 5
• 229910017604 nitric acid Inorganic materials 0.000 description 5
• 239000012071 phase Substances 0.000 description 5
• 230000008569 process Effects 0.000 description 5
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 5
• 229960003010 sodium sulfate Drugs 0.000 description 5
• 241000894007 species Species 0.000 description 5
• 125000005555 sulfoximide group Chemical group 0.000 description 5
• 239000000454 talc Substances 0.000 description 5
• 229910052623 talc Inorganic materials 0.000 description 5
• 230000009466 transformation Effects 0.000 description 5
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
• IBXSKLWVJHRUJN-CYBMUJFWSA-N (5r)-3-[3-fluoro-4-(thian-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC=C1C1CCSCC1 IBXSKLWVJHRUJN-CYBMUJFWSA-N 0.000 description 4
• OJVAMHKKJGICOG-UHFFFAOYSA-N 2,5-hexanedione Chemical compound CC(=O)CCC(C)=O OJVAMHKKJGICOG-UHFFFAOYSA-N 0.000 description 4
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 4
• BRUZQRBVNRKLJG-UHFFFAOYSA-N 2-methylpropyl carbamate Chemical compound CC(C)COC(N)=O BRUZQRBVNRKLJG-UHFFFAOYSA-N 0.000 description 4
• ZPOODPZCZLCUAN-UHFFFAOYSA-N 3,4-dihydro-1h-pyridin-2-one Chemical class O=C1CCC=CN1 ZPOODPZCZLCUAN-UHFFFAOYSA-N 0.000 description 4
• 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 4
• JGYJZHYTADCWIK-UHFFFAOYSA-N 6-nitro-3h-1,3-benzoxazol-2-one Chemical class [O-][N+](=O)C1=CC=C2NC(=O)OC2=C1 JGYJZHYTADCWIK-UHFFFAOYSA-N 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• 239000007832 Na2SO4 Substances 0.000 description 4
• YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• 239000007868 Raney catalyst Substances 0.000 description 4
• 229910000564 Raney nickel Inorganic materials 0.000 description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
• VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
• 150000001412 amines Chemical class 0.000 description 4
• 239000007864 aqueous solution Substances 0.000 description 4
• 239000011230 binding agent Substances 0.000 description 4
• IIDDDIKGSSYACC-MRXNPFEDSA-N butyl (5r)-3-(3-fluoro-4-thiomorpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCCCC)CN1C(C=C1F)=CC=C1N1CCSCC1 IIDDDIKGSSYACC-MRXNPFEDSA-N 0.000 description 4
• 238000005859 coupling reaction Methods 0.000 description 4
• 239000003085 diluting agent Substances 0.000 description 4
• 235000013355 food flavoring agent Nutrition 0.000 description 4
• 235000019253 formic acid Nutrition 0.000 description 4
• 238000001802 infusion Methods 0.000 description 4
• CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 4
• PEKIMFLEPUOQJW-GFCCVEGCSA-N methyl (5r)-3-(3,5-difluoro-4-thiomorpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C(C=C1F)=CC(F)=C1N1CCSCC1 PEKIMFLEPUOQJW-GFCCVEGCSA-N 0.000 description 4
• KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 4
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
• 150000007530 organic bases Chemical class 0.000 description 4
• 235000015320 potassium carbonate Nutrition 0.000 description 4
• 229960002668 sodium chloride Drugs 0.000 description 4
• 235000000346 sugar Nutrition 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• 125000003396 thiol group Chemical class [H]S* 0.000 description 4
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
• VDHNKGVVXBUCFR-UHFFFAOYSA-N trimethyl(pyridin-3-yl)stannane Chemical compound C[Sn](C)(C)C1=CC=CN=C1 VDHNKGVVXBUCFR-UHFFFAOYSA-N 0.000 description 4
• BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 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
• 239000003981 vehicle Substances 0.000 description 4
• WITWMANCORVTOM-SNVBAGLBSA-N (5r)-2-oxo-3-(2-oxo-3-propan-2-yl-1,3-benzothiazol-6-yl)-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(C(C)C)C2=CC=C1N1C[C@H](C(N)=O)OC1=O WITWMANCORVTOM-SNVBAGLBSA-N 0.000 description 3
• RJSZELVEVUFBGW-MRVPVSSYSA-N (5r)-3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C1=CC=C(I)C(F)=C1 RJSZELVEVUFBGW-MRVPVSSYSA-N 0.000 description 3
• PTTUMBGORBMNBN-UHFFFAOYSA-N 1,2,3-trifluoro-5-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(F)=C(F)C(F)=C1 PTTUMBGORBMNBN-UHFFFAOYSA-N 0.000 description 3
• BXQNSPXDWSNUKE-UHFFFAOYSA-N 1,3-benzothiazole 1-oxide Chemical class C1=CC=C2S(=O)C=NC2=C1 BXQNSPXDWSNUKE-UHFFFAOYSA-N 0.000 description 3
• PAPNRQCYSFBWDI-UHFFFAOYSA-N 2,5-Dimethyl-1H-pyrrole Chemical compound CC1=CC=C(C)N1 PAPNRQCYSFBWDI-UHFFFAOYSA-N 0.000 description 3
• DOPJTDJKZNWLRB-UHFFFAOYSA-N 2-Amino-5-nitrophenol Chemical compound NC1=CC=C([N+]([O-])=O)C=C1O DOPJTDJKZNWLRB-UHFFFAOYSA-N 0.000 description 3
• ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 3
• KQOIBXZRCYFZSO-UHFFFAOYSA-N 3,5-difluoroaniline Chemical compound NC1=CC(F)=CC(F)=C1 KQOIBXZRCYFZSO-UHFFFAOYSA-N 0.000 description 3
• CJXCQSBVVCCJCG-UHFFFAOYSA-N 3-methyl-6-nitro-1,3-benzothiazol-2-one Chemical compound C1=C([N+]([O-])=O)C=C2SC(=O)N(C)C2=C1 CJXCQSBVVCCJCG-UHFFFAOYSA-N 0.000 description 3
• QFGPTCRZVHKSFY-UHFFFAOYSA-N 4-(3,6-dihydro-2h-thiopyran-4-yl)-3,5-difluoroaniline Chemical compound FC1=CC(N)=CC(F)=C1C1=CCSCC1 QFGPTCRZVHKSFY-UHFFFAOYSA-N 0.000 description 3
• RQXQMUUSQGCLPL-UHFFFAOYSA-N 4-thiomorpholin-4-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCSCC1 RQXQMUUSQGCLPL-UHFFFAOYSA-N 0.000 description 3
• FPNLXQSOWBNXCN-UHFFFAOYSA-N 6-amino-3-methyl-1,3-benzoxazol-2-one Chemical compound C1=C(N)C=C2OC(=O)N(C)C2=C1 FPNLXQSOWBNXCN-UHFFFAOYSA-N 0.000 description 3
• 229920001817 Agar Polymers 0.000 description 3
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 3
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 3
• 239000002202 Polyethylene glycol Substances 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• 239000002671 adjuvant Substances 0.000 description 3
• 239000008272 agar Substances 0.000 description 3
• 230000029936 alkylation Effects 0.000 description 3
• 238000005804 alkylation reaction Methods 0.000 description 3
• 238000005576 amination reaction Methods 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• BEDZPJTYYUIWHJ-CQSZACIVSA-N butyl (5r)-3-(3-ethyl-2-oxo-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCCCC)CN1C1=CC=C(N(CC)C(=O)O2)C2=C1 BEDZPJTYYUIWHJ-CQSZACIVSA-N 0.000 description 3
• 229940110456 cocoa butter Drugs 0.000 description 3
• 235000019868 cocoa butter Nutrition 0.000 description 3
• 238000001816 cooling Methods 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 238000010511 deprotection reaction Methods 0.000 description 3
• 230000005595 deprotonation Effects 0.000 description 3
• 238000010537 deprotonation reaction Methods 0.000 description 3
• 238000010790 dilution Methods 0.000 description 3
• 239000012895 dilution Substances 0.000 description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
• 239000008298 dragée Substances 0.000 description 3
• 239000003937 drug carrier Substances 0.000 description 3
• LSGWSXRILNPXKJ-SCSAIBSYSA-N ethyl (2r)-oxirane-2-carboxylate Chemical compound CCOC(=O)[C@H]1CO1 LSGWSXRILNPXKJ-SCSAIBSYSA-N 0.000 description 3
• 229940093476 ethylene glycol Drugs 0.000 description 3
• 125000001207 fluorophenyl group Chemical group 0.000 description 3
• 125000000524 functional group Chemical group 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 239000012535 impurity Substances 0.000 description 3
• FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 3
• 150000002576 ketones Chemical class 0.000 description 3
• 239000002502 liposome Substances 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 3
• JMGXCRNHQKBBJV-SNVBAGLBSA-N methyl (5r)-3-(3-ethyl-4-fluoro-2-oxo-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound C1=C2OC(=O)N(CC)C2=C(F)C=C1N1C[C@H](C(=O)OC)OC1=O JMGXCRNHQKBBJV-SNVBAGLBSA-N 0.000 description 3
• SVYBLUXANJBWGO-SECBINFHSA-N methyl (5r)-3-(3-fluoro-4-iodophenyl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C1=CC=C(I)C(F)=C1 SVYBLUXANJBWGO-SECBINFHSA-N 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• 239000003960 organic solvent Substances 0.000 description 3
• 239000007800 oxidant agent Substances 0.000 description 3
• 230000003647 oxidation Effects 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 230000001590 oxidative effect Effects 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
• 230000035484 reaction time Effects 0.000 description 3
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 3
• 239000000600 sorbitol Substances 0.000 description 3
• 235000010356 sorbitol Nutrition 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 238000003860 storage Methods 0.000 description 3
• 150000003457 sulfones Chemical class 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 3
• CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 3
• 239000001974 tryptic soy broth Substances 0.000 description 3
• 108010050327 trypticase-soy broth Proteins 0.000 description 3
• 210000002268 wool Anatomy 0.000 description 3
• 229910052727 yttrium Inorganic materials 0.000 description 3
• DEGCJOSHUYIYOZ-GFCCVEGCSA-N (5R)-2-oxo-3-(4-thiomorpholin-4-ylphenyl)-1,3-oxazolidine-5-carboxylic acid Chemical compound O=C1O[C@@H](C(=O)O)CN1C1=CC=C(N2CCSCC2)C=C1 DEGCJOSHUYIYOZ-GFCCVEGCSA-N 0.000 description 2
• PFJNWSSPBAXUQD-SNVBAGLBSA-N (5r)-3-(3-ethyl-2-oxo-1,3-benzothiazol-6-yl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(CC)C2=CC=C1N1C[C@H](C(=O)NC)OC1=O PFJNWSSPBAXUQD-SNVBAGLBSA-N 0.000 description 2
• UJXLGKPWPSYMAO-MRVPVSSYSA-N (5r)-3-(3-ethyl-4-fluoro-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(CC)C2=C(F)C=C1N1C[C@H](C(N)=O)OC1=O UJXLGKPWPSYMAO-MRVPVSSYSA-N 0.000 description 2
• DIDJTOBWBNSVKL-SSDOTTSWSA-N (5r)-3-(3-fluoro-4-iodophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one Chemical compound O=C1O[C@@H](CO)CN1C1=CC=C(I)C(F)=C1 DIDJTOBWBNSVKL-SSDOTTSWSA-N 0.000 description 2
• COFLUECJJTXILC-LJQANCHMSA-N (5r)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-n-phenylmethoxy-1,3-oxazolidine-5-carboxamide Chemical compound FC1=CC(N2C(O[C@H](C2)C(=O)NOCC=2C=CC=CC=2)=O)=CC=C1N1CCOCC1 COFLUECJJTXILC-LJQANCHMSA-N 0.000 description 2
• NHWIOEUMJBBCOE-XWCOYVICSA-N (5r)-3-(3-fluoro-4-trimethylstannylphenyl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C(F)C([Sn](C)(C)C)=CC=C1N1C(=O)O[C@@H](C(N)=O)C1 NHWIOEUMJBBCOE-XWCOYVICSA-N 0.000 description 2
• NRYRVJNSXGWOMJ-SECBINFHSA-N (5r)-3-(3-methyl-2-oxo-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2OC(=O)N(C)C2=CC=C1N1C[C@H](C(N)=O)OC1=O NRYRVJNSXGWOMJ-SECBINFHSA-N 0.000 description 2
• RUBQQRMAWLSCCJ-UHFFFAOYSA-N 1,2-difluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1 RUBQQRMAWLSCCJ-UHFFFAOYSA-N 0.000 description 2
• NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 description 2
• BMXFDVAJYBTGRC-UHFFFAOYSA-N 1-(2-fluoro-4-nitrophenyl)piperidin-4-one Chemical compound FC1=CC([N+](=O)[O-])=CC=C1N1CCC(=O)CC1 BMXFDVAJYBTGRC-UHFFFAOYSA-N 0.000 description 2
• WLFGGJFWKXTOGJ-UHFFFAOYSA-N 2,3-dihydroindol-1-amine Chemical compound C1=CC=C2N(N)CCC2=C1 WLFGGJFWKXTOGJ-UHFFFAOYSA-N 0.000 description 2
• 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 2
• UJDSRXSZJCJVCS-UHFFFAOYSA-N 2-amino-5-nitrobenzenethiol Chemical compound NC1=CC=C([N+]([O-])=O)C=C1S UJDSRXSZJCJVCS-UHFFFAOYSA-N 0.000 description 2
• BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 2
• WRPUGUVJZWWEJI-UHFFFAOYSA-N 2-fluoro-6-phenylmethoxybenzamide Chemical compound NC(=O)C1=C(F)C=CC=C1OCC1=CC=CC=C1 WRPUGUVJZWWEJI-UHFFFAOYSA-N 0.000 description 2
• YRRZGBOZBIVMJT-UHFFFAOYSA-N 2-fluoroethanamine;hydron;chloride Chemical compound Cl.NCCF YRRZGBOZBIVMJT-UHFFFAOYSA-N 0.000 description 2
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
• NXYOCCGTKSAZSI-UHFFFAOYSA-N 2-methylpropyl n-(3,5-difluorophenyl)carbamate Chemical compound CC(C)COC(=O)NC1=CC(F)=CC(F)=C1 NXYOCCGTKSAZSI-UHFFFAOYSA-N 0.000 description 2
• RLWSHMZGSITDJU-UHFFFAOYSA-N 2-methylpropyl n-(4-bromophenyl)carbamate Chemical compound CC(C)COC(=O)NC1=CC=C(Br)C=C1 RLWSHMZGSITDJU-UHFFFAOYSA-N 0.000 description 2
• NXPOFLDHVSJZRH-UHFFFAOYSA-N 2-methylpropyl n-[3-fluoro-4-(thian-4-yl)phenyl]carbamate Chemical compound FC1=CC(NC(=O)OCC(C)C)=CC=C1C1CCSCC1 NXPOFLDHVSJZRH-UHFFFAOYSA-N 0.000 description 2
• JNWGSMFRONFIOK-UHFFFAOYSA-N 2-methylpropyl n-[4-(3,6-dihydro-2h-thiopyran-4-yl)-3,5-difluorophenyl]carbamate Chemical compound FC1=CC(NC(=O)OCC(C)C)=CC(F)=C1C1=CCSCC1 JNWGSMFRONFIOK-UHFFFAOYSA-N 0.000 description 2
• FCNMUAPZQUTXIQ-UHFFFAOYSA-N 2-methylpropyl n-[4-(thian-4-yl)phenyl]carbamate Chemical compound C1=CC(NC(=O)OCC(C)C)=CC=C1C1CCSCC1 FCNMUAPZQUTXIQ-UHFFFAOYSA-N 0.000 description 2
• QISAUDWTBBNJIR-UHFFFAOYSA-N 2-phenylmethoxyacetyl chloride Chemical compound ClC(=O)COCC1=CC=CC=C1 QISAUDWTBBNJIR-UHFFFAOYSA-N 0.000 description 2
• IVEHJYFWFOGHRD-UHFFFAOYSA-N 2h-thiadiazin-5-one Chemical compound O=C1CSNN=C1 IVEHJYFWFOGHRD-UHFFFAOYSA-N 0.000 description 2
• ATVJJNGVPSKBGO-UHFFFAOYSA-N 3,4-dihydro-2h-thiopyran Chemical compound C1CSC=CC1 ATVJJNGVPSKBGO-UHFFFAOYSA-N 0.000 description 2
• UJDAHQIWJXFPDS-UHFFFAOYSA-N 3-(4-amino-2,6-difluorophenyl)-3-methylazetidin-2-one Chemical compound FC=1C=C(N)C=C(F)C=1C1(C)CNC1=O UJDAHQIWJXFPDS-UHFFFAOYSA-N 0.000 description 2
• IXECKIKGIGZUEO-UHFFFAOYSA-N 3-ethyl-6-nitro-1,3-benzothiazol-2-one Chemical compound C1=C([N+]([O-])=O)C=C2SC(=O)N(CC)C2=C1 IXECKIKGIGZUEO-UHFFFAOYSA-N 0.000 description 2
• KASMUJRVIWHUJM-UHFFFAOYSA-N 3-ethyl-6-nitro-1,3-benzoxazol-2-one Chemical compound C1=C([N+]([O-])=O)C=C2OC(=O)N(CC)C2=C1 KASMUJRVIWHUJM-UHFFFAOYSA-N 0.000 description 2
• PJPQOKJRZYFFHH-UHFFFAOYSA-N 3-fluoro-4-(thian-4-yl)aniline Chemical compound FC1=CC(N)=CC=C1C1CCSCC1 PJPQOKJRZYFFHH-UHFFFAOYSA-N 0.000 description 2
• VUKIKMHYSUVLQB-UHFFFAOYSA-N 3-methyl-6-nitro-1,3-benzoxazol-2-one Chemical compound C1=C([N+]([O-])=O)C=C2OC(=O)N(C)C2=C1 VUKIKMHYSUVLQB-UHFFFAOYSA-N 0.000 description 2
• LLPPBKRBTDHNRL-UHFFFAOYSA-N 4-(2,5-dihydropyrrol-1-yl)-3,5-difluoroaniline Chemical compound FC1=CC(N)=CC(F)=C1N1CC=CC1 LLPPBKRBTDHNRL-UHFFFAOYSA-N 0.000 description 2
• HZQGZVKUVGTJCE-UHFFFAOYSA-N 4-(2,6-difluorophenyl)-1,4-thiazinane 1,1-dioxide Chemical compound FC1=CC=CC(F)=C1N1CCS(=O)(=O)CC1 HZQGZVKUVGTJCE-UHFFFAOYSA-N 0.000 description 2
• FTNAGFKVVUKXFW-UHFFFAOYSA-N 4-(thian-4-yl)aniline Chemical compound C1=CC(N)=CC=C1C1CCSCC1 FTNAGFKVVUKXFW-UHFFFAOYSA-N 0.000 description 2
• WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 2
• YDCVXLYRCGKFBR-UHFFFAOYSA-N 5-nitro-2-(propan-2-ylamino)phenol Chemical compound CC(C)NC1=CC=C([N+]([O-])=O)C=C1O YDCVXLYRCGKFBR-UHFFFAOYSA-N 0.000 description 2
• FAQSRBYRLPRXNK-UHFFFAOYSA-N 6-amino-3-ethyl-1,3-benzoxazol-2-one Chemical compound C1=C(N)C=C2OC(=O)N(CC)C2=C1 FAQSRBYRLPRXNK-UHFFFAOYSA-N 0.000 description 2
• STDGBEKVJJKVNB-UHFFFAOYSA-N 6-amino-3-methyl-1,3-benzothiazol-2-one Chemical compound C1=C(N)C=C2SC(=O)N(C)C2=C1 STDGBEKVJJKVNB-UHFFFAOYSA-N 0.000 description 2
• GRCUAQZMYNLZIR-UHFFFAOYSA-N 6-amino-3-propan-2-yl-1,3-benzothiazol-2-one Chemical compound C1=C(N)C=C2SC(=O)N(C(C)C)C2=C1 GRCUAQZMYNLZIR-UHFFFAOYSA-N 0.000 description 2
• CPTMCHKHHPBEIO-UHFFFAOYSA-N 6-amino-3-propan-2-yl-1,3-benzoxazol-2-one Chemical compound C1=C(N)C=C2OC(=O)N(C(C)C)C2=C1 CPTMCHKHHPBEIO-UHFFFAOYSA-N 0.000 description 2
• QCJVUJJQCIHQMJ-UHFFFAOYSA-N 6-nitro-3-propan-2-yl-1,3-benzothiazol-2-one Chemical compound C1=C([N+]([O-])=O)C=C2SC(=O)N(C(C)C)C2=C1 QCJVUJJQCIHQMJ-UHFFFAOYSA-N 0.000 description 2
• PCJXQVJIUFVRTH-UHFFFAOYSA-N 6-nitro-3-propan-2-yl-1,3-benzoxazol-2-one Chemical compound C1=C([N+]([O-])=O)C=C2OC(=O)N(C(C)C)C2=C1 PCJXQVJIUFVRTH-UHFFFAOYSA-N 0.000 description 2
• 241000894006 Bacteria Species 0.000 description 2
• 208000035143 Bacterial infection Diseases 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
• 229920001353 Dextrin Polymers 0.000 description 2
• 239000004375 Dextrin Substances 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• YLNSNVGRSIOCEU-ZCFIWIBFSA-N [(2r)-oxiran-2-yl]methyl butanoate Chemical compound CCCC(=O)OC[C@H]1CO1 YLNSNVGRSIOCEU-ZCFIWIBFSA-N 0.000 description 2
• IGUGLOQBLCMITB-UHFFFAOYSA-N [N].C1=CC=C2NCCC2=C1 Chemical compound [N].C1=CC=C2NCCC2=C1 IGUGLOQBLCMITB-UHFFFAOYSA-N 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 238000002814 agar dilution Methods 0.000 description 2
• 150000001408 amides Chemical class 0.000 description 2
• 125000003277 amino group Chemical group 0.000 description 2
• 150000001448 anilines Chemical class 0.000 description 2
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 150000001503 aryl iodides Chemical class 0.000 description 2
• CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
• 208000022362 bacterial infectious disease Diseases 0.000 description 2
• LFGHHOFSKMEHJE-GOSISDBHSA-N benzyl (2r)-5-(2,5-dimethylpyrrol-1-yl)-2-methyl-2,3-dihydroindole-1-carboxylate Chemical compound C([C@H]1C)C2=CC(N3C(=CC=C3C)C)=CC=C2N1C(=O)OCC1=CC=CC=C1 LFGHHOFSKMEHJE-GOSISDBHSA-N 0.000 description 2
• HWRWRZKGEJIZHJ-CYBMUJFWSA-N butyl (5r)-3-(3-methyl-2-oxo-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical group O=C1O[C@@H](C(=O)OCCCC)CN1C1=CC=C(N(C)C(=O)O2)C2=C1 HWRWRZKGEJIZHJ-CYBMUJFWSA-N 0.000 description 2
• SNQFOJYVVZVUNK-MRXNPFEDSA-N butyl (5r)-3-[3,5-difluoro-4-(thian-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCCCC)CN1C(C=C1F)=CC(F)=C1C1CCSCC1 SNQFOJYVVZVUNK-MRXNPFEDSA-N 0.000 description 2
• SQSCOQUBAWEKPK-QGZVFWFLSA-N butyl (5r)-3-[3-fluoro-4-(thian-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical group O=C1O[C@@H](C(=O)OCCCC)CN1C(C=C1F)=CC=C1C1CCSCC1 SQSCOQUBAWEKPK-QGZVFWFLSA-N 0.000 description 2
• RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
• 235000010216 calcium carbonate Nutrition 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 150000004657 carbamic acid derivatives Chemical class 0.000 description 2
• OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical compound NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 150000003857 carboxamides Chemical class 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
• 238000001311 chemical methods and process Methods 0.000 description 2
• KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
• OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
• 238000000576 coating method Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 235000019425 dextrin Nutrition 0.000 description 2
• 125000004212 difluorophenyl group Chemical group 0.000 description 2
• 238000004090 dissolution Methods 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• MPCPJKAPOGWZEV-CQSZACIVSA-N ethyl (5r)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCC)CN1C(C=C1F)=CC=C1N1CCOCC1 MPCPJKAPOGWZEV-CQSZACIVSA-N 0.000 description 2
• FDWMYEAYYQHOJQ-UHFFFAOYSA-N ethyl 2-cyano-2-(2,6-difluoro-4-nitrophenyl)propanoate Chemical compound CCOC(=O)C(C)(C#N)C1=C(F)C=C([N+]([O-])=O)C=C1F FDWMYEAYYQHOJQ-UHFFFAOYSA-N 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 238000000605 extraction Methods 0.000 description 2
• 239000010685 fatty oil Substances 0.000 description 2
• 125000001153 fluoro group Chemical group F* 0.000 description 2
• 238000007306 functionalization reaction Methods 0.000 description 2
• KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 238000000338 in vitro Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• 229960003646 lysine Drugs 0.000 description 2
• IPMQCQXLQFRMDX-SECBINFHSA-N methyl (2r)-3-[(3-ethyl-4-fluoro-2-oxo-1,3-benzoxazol-6-yl)amino]-2-hydroxypropanoate Chemical compound C1=C(NC[C@@H](O)C(=O)OC)C=C2OC(=O)N(CC)C2=C1F IPMQCQXLQFRMDX-SECBINFHSA-N 0.000 description 2
• PFBFPLCCCCLNFC-LLVKDONJSA-N methyl (5r)-2-oxo-3-(2-oxo-3-propan-2-yl-1,3-benzothiazol-6-yl)-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C1=CC=C(N(C(C)C)C(=O)S2)C2=C1 PFBFPLCCCCLNFC-LLVKDONJSA-N 0.000 description 2
• FBRZGPIEXBNAOC-NOZJJQNGSA-N methyl (5r)-3-[(2r)-1-(2-hydroxyacetyl)-2-methyl-2,3-dihydroindol-5-yl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C1=CC=C(N([C@H](C)C2)C(=O)CO)C2=C1 FBRZGPIEXBNAOC-NOZJJQNGSA-N 0.000 description 2
• NAHAZYALLPATSD-FOIQADDNSA-N methyl (5r)-3-[(2r)-2-methyl-1-(2-phenylmethoxyacetyl)-2,3-dihydroindol-5-yl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C1=CC=C(N([C@H](C)C2)C(=O)COCC=3C=CC=CC=3)C2=C1 NAHAZYALLPATSD-FOIQADDNSA-N 0.000 description 2
• HGNUPQJZGKBDEZ-AUUYWEPGSA-N methyl (5r)-3-[(2r)-2-methyl-1-phenylmethoxycarbonyl-2,3-dihydroindol-5-yl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C1=CC=C(N([C@H](C)C2)C(=O)OCC=3C=CC=CC=3)C2=C1 HGNUPQJZGKBDEZ-AUUYWEPGSA-N 0.000 description 2
• FBPSBKVDOJPWNJ-CQSZACIVSA-N methyl (5r)-3-[3-fluoro-4-(thian-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical group O=C1O[C@@H](C(=O)OC)CN1C(C=C1F)=CC=C1C1CCSCC1 FBPSBKVDOJPWNJ-CQSZACIVSA-N 0.000 description 2
• YEFGZVYURYULPT-CQSZACIVSA-N methyl (5r)-3-[4-(3,6-dihydro-2h-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C(C=C1F)=CC=C1C1=CCSCC1 YEFGZVYURYULPT-CQSZACIVSA-N 0.000 description 2
• BSTNQJIXFZPKKI-MRXNPFEDSA-N methyl (5r)-3-[4-(5,7-dihydropyrrolo[3,4-b]pyridin-6-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C(C=C1F)=CC=C1N1CC2=NC=CC=C2C1 BSTNQJIXFZPKKI-MRXNPFEDSA-N 0.000 description 2
• YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
• YJFVEQAGDFFOCA-UHFFFAOYSA-N methyl 3-(4-amino-2,6-difluorophenyl)-3-methylazetidine-1-carboxylate Chemical compound C1N(C(=O)OC)CC1(C)C1=C(F)C=C(N)C=C1F YJFVEQAGDFFOCA-UHFFFAOYSA-N 0.000 description 2
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 125000002757 morpholinyl group Chemical group 0.000 description 2
• 238000006396 nitration reaction Methods 0.000 description 2
• 231100000252 nontoxic Toxicity 0.000 description 2
• 230000003000 nontoxic effect Effects 0.000 description 2
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 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
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 239000001814 pectin Substances 0.000 description 2
• 229920001277 pectin Polymers 0.000 description 2
• 235000010987 pectin Nutrition 0.000 description 2
• 235000019271 petrolatum Nutrition 0.000 description 2
• 239000003495 polar organic solvent Substances 0.000 description 2
• 229920000642 polymer Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 2
• 235000013772 propylene glycol Nutrition 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 239000011550 stock solution Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 238000013268 sustained release Methods 0.000 description 2
• 239000012730 sustained-release form Substances 0.000 description 2
• 230000009885 systemic effect Effects 0.000 description 2
• YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
• YODQQARABJQLIP-UHFFFAOYSA-N thian-4-ol Chemical compound OC1CCSCC1 YODQQARABJQLIP-UHFFFAOYSA-N 0.000 description 2
• 239000002562 thickening agent Substances 0.000 description 2
• 229930192474 thiophene Natural products 0.000 description 2
• 125000000464 thioxo group Chemical group S=* 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 238000000844 transformation Methods 0.000 description 2
• 238000011269 treatment regimen Methods 0.000 description 2
• URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
• GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 2
• 229940056345 tums Drugs 0.000 description 2
• 239000003039 volatile agent Substances 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• ZZIZDBJWSSJASG-ZCFIWIBFSA-N (2r)-2-methyl-2,3-dihydro-1h-indol-5-amine Chemical compound NC1=CC=C2N[C@H](C)CC2=C1 ZZIZDBJWSSJASG-ZCFIWIBFSA-N 0.000 description 1
• 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 1
• RIQJBBRXFAYIQJ-UHFFFAOYSA-N (3-fluoro-4-morpholin-4-ylphenyl)carbamic acid Chemical compound FC1=CC(NC(=O)O)=CC=C1N1CCOCC1 RIQJBBRXFAYIQJ-UHFFFAOYSA-N 0.000 description 1
• STJQRLLBZJAZAU-LLVKDONJSA-N (5R)-3-(3,5-difluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxylic acid Chemical compound O=C1O[C@@H](C(=O)O)CN1C(C=C1F)=CC(F)=C1N1CCOCC1 STJQRLLBZJAZAU-LLVKDONJSA-N 0.000 description 1
• LQLWOFZUDKPSCY-SNVBAGLBSA-N (5R)-3-(4-fluoro-2-oxo-3-propan-2-yl-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylic acid Chemical compound C1=C2OC(=O)N(C(C)C)C2=C(F)C=C1N1C[C@H](C(O)=O)OC1=O LQLWOFZUDKPSCY-SNVBAGLBSA-N 0.000 description 1
• GPSQQJNZZIFDPK-CYBMUJFWSA-N (5R)-3-[3-fluoro-4-(thian-4-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxylic acid Chemical compound O=C1O[C@@H](C(=O)O)CN1C(C=C1F)=CC=C1C1CCSCC1 GPSQQJNZZIFDPK-CYBMUJFWSA-N 0.000 description 1
• UYNQRPSGYOWXKS-CYBMUJFWSA-N (5r)-2-oxo-3-[4-(thian-4-yl)phenyl]-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C1=CC=C(C2CCSCC2)C=C1 UYNQRPSGYOWXKS-CYBMUJFWSA-N 0.000 description 1
• MDCWSPZMNORBOW-LLVKDONJSA-N (5r)-3-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C=1C=C2N(C)C(=O)CCC2=CC=1N1C[C@H](C(N)=O)OC1=O MDCWSPZMNORBOW-LLVKDONJSA-N 0.000 description 1
• YWZJCWNONYMQIH-SECBINFHSA-N (5r)-3-(2,2-difluoro-4-methyl-3-oxo-1,4-benzoxazin-7-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C=1C=C2N(C)C(=O)C(F)(F)OC2=CC=1N1C[C@H](C(N)=O)OC1=O YWZJCWNONYMQIH-SECBINFHSA-N 0.000 description 1
• MBMYESFCZXOCFX-SNVBAGLBSA-N (5r)-3-(2,2-difluoro-4-methyl-3-oxo-1,4-benzoxazin-7-yl)-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC=C(N(C)C(=O)C(F)(F)O2)C2=C1 MBMYESFCZXOCFX-SNVBAGLBSA-N 0.000 description 1
• DJUZFAHLCSKESR-LLVKDONJSA-N (5r)-3-(3,5-difluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC(F)=C1N1CCOCC1 DJUZFAHLCSKESR-LLVKDONJSA-N 0.000 description 1
• NMUWCDITKDTXCY-SECBINFHSA-N (5r)-3-(3-ethyl-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(CC)C2=CC=C1N1C[C@H](C(N)=O)OC1=O NMUWCDITKDTXCY-SECBINFHSA-N 0.000 description 1
• UQPYLSOHZOWISH-GFCCVEGCSA-N (5r)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxylic acid Chemical compound O=C1O[C@@H](C(=O)O)CN1C(C=C1F)=CC=C1N1CCOCC1 UQPYLSOHZOWISH-GFCCVEGCSA-N 0.000 description 1
• RQABAESQBKRWLX-OAHLLOKOSA-N (5r)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-n-prop-2-enyl-1,3-oxazolidine-5-carboxamide Chemical compound FC1=CC(N2C(O[C@H](C2)C(=O)NCC=C)=O)=CC=C1N1CCOCC1 RQABAESQBKRWLX-OAHLLOKOSA-N 0.000 description 1
• QQIXWRAJTSBLER-OAHLLOKOSA-N (5r)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-n-propyl-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NCCC)CN1C(C=C1F)=CC=C1N1CCOCC1 QQIXWRAJTSBLER-OAHLLOKOSA-N 0.000 description 1
• QRTUBJBBRLVBHE-CYBMUJFWSA-N (5r)-3-(3-fluoro-4-morpholin-4-ylphenyl)-n-methoxy-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NOC)CN1C(C=C1F)=CC=C1N1CCOCC1 QRTUBJBBRLVBHE-CYBMUJFWSA-N 0.000 description 1
• UROLCMGOKNJOLW-CYBMUJFWSA-N (5r)-3-(3-fluoro-4-pyridin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C1=CC=C(C=2C=CN=CC=2)C(F)=C1 UROLCMGOKNJOLW-CYBMUJFWSA-N 0.000 description 1
• OZEPAARJWXEJIN-SECBINFHSA-N (5r)-3-(4-fluoro-2-oxo-3-propan-2-yl-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C1=C2SC(=O)N(C(C)C)C2=C(F)C=C1N1C[C@H](C(N)=O)OC1=O OZEPAARJWXEJIN-SECBINFHSA-N 0.000 description 1
• UFAPAAHPPROOHH-PRHODGIISA-N (5r)-3-[(2r)-1-formyl-2-methyl-2,3-dihydroindol-5-yl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound C([C@H](N(C1=CC=2)C=O)C)C1=CC=2N1C[C@H](C(N)=O)OC1=O UFAPAAHPPROOHH-PRHODGIISA-N 0.000 description 1
• BYNOFGTZDYUNLO-JHJMLUEUSA-N (5r)-3-[2-(2-fluoropiperazin-1-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C1=CC=CC=C1N1C(F)CNCC1 BYNOFGTZDYUNLO-JHJMLUEUSA-N 0.000 description 1
• JPERMSZUEANIQN-LLVKDONJSA-N (5r)-3-[3,5-difluoro-4-(1-formyl-3-methylazetidin-3-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound FC=1C=C(N2C(O[C@H](C2)C(N)=O)=O)C=C(F)C=1C1(C)CN(C=O)C1 JPERMSZUEANIQN-LLVKDONJSA-N 0.000 description 1
• SINDJTCEVXDDKF-GFCCVEGCSA-N (5r)-3-[3,5-difluoro-4-(1-imino-1-oxo-1,4-thiazinan-4-yl)phenyl]-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C(C=C1F)=CC(F)=C1N1CCS(=N)(=O)CC1 SINDJTCEVXDDKF-GFCCVEGCSA-N 0.000 description 1
• WZOZSVFAVGZQTI-CQSZACIVSA-N (5r)-3-[3-(2-hydroxyacetyl)-1,2,4,5-tetrahydro-3-benzazepin-7-yl]-n-methyl-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC=C(CCN(CC2)C(=O)CO)C2=C1 WZOZSVFAVGZQTI-CQSZACIVSA-N 0.000 description 1
• OAZCXHHETMOQAV-GFCCVEGCSA-N (5r)-3-[3-fluoro-4-(thian-4-yl)phenyl]-5-(hydroxymethyl)-1,3-oxazolidin-2-one Chemical compound O=C1O[C@@H](CO)CN1C(C=C1F)=CC=C1C1CCSCC1 OAZCXHHETMOQAV-GFCCVEGCSA-N 0.000 description 1
• GNUMQVDIQCVLSO-CYBMUJFWSA-N (5r)-3-[3-fluoro-4-[4-(2-hydroxyacetyl)piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CO)CC1 GNUMQVDIQCVLSO-CYBMUJFWSA-N 0.000 description 1
• DXDRDTGEPCSZKE-LLVKDONJSA-N (5r)-3-[4-(2,5-dihydropyrrol-1-yl)-3,5-difluorophenyl]-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)N)CN1C(C=C1F)=CC(F)=C1N1CC=CC1 DXDRDTGEPCSZKE-LLVKDONJSA-N 0.000 description 1
• USCNSXWQKOQGOB-SNVBAGLBSA-N (5r)-n-ethyl-3-(3-methyl-2-oxo-1,3-benzothiazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NCC)CN1C1=CC=C(N(C)C(=O)S2)C2=C1 USCNSXWQKOQGOB-SNVBAGLBSA-N 0.000 description 1
• ASPIDQFPXGOSBA-GFCCVEGCSA-N (5r)-n-methyl-2-oxo-3-(2-oxo-3-propan-2-yl-1,3-benzoxazol-6-yl)-1,3-oxazolidine-5-carboxamide Chemical compound O=C1O[C@@H](C(=O)NC)CN1C1=CC=C(N(C(C)C)C(=O)O2)C2=C1 ASPIDQFPXGOSBA-GFCCVEGCSA-N 0.000 description 1
• DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• SCZNXLWKYFICFV-UHFFFAOYSA-N 1,2,3,4,5,7,8,9-octahydropyrido[1,2-b]diazepine Chemical compound C1CCCNN2CCCC=C21 SCZNXLWKYFICFV-UHFFFAOYSA-N 0.000 description 1
• ARCACZWMYGILNI-UHFFFAOYSA-N 1,2,3-trifluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1F ARCACZWMYGILNI-UHFFFAOYSA-N 0.000 description 1
• 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 description 1
• BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
• KNWCDYSKJSREAQ-UHFFFAOYSA-N 1,3-oxazolidine-2-carboxylic acid Chemical compound OC(=O)C1NCCO1 KNWCDYSKJSREAQ-UHFFFAOYSA-N 0.000 description 1
• AXTPKYQMUDUCFW-UHFFFAOYSA-N 1,3-thiazole 1,1-dioxide Chemical compound O=S1(=O)C=CN=C1 AXTPKYQMUDUCFW-UHFFFAOYSA-N 0.000 description 1
• WMKGGPCROCCUDY-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one Chemical compound C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 WMKGGPCROCCUDY-UHFFFAOYSA-N 0.000 description 1
• IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
• VUCWMAJEUOWLEY-UHFFFAOYSA-N 1-$l^{1}-azanylpiperidine Chemical compound [N]N1CCCCC1 VUCWMAJEUOWLEY-UHFFFAOYSA-N 0.000 description 1
• JLTWGXIEPHGMSB-UHFFFAOYSA-N 1-(2,6-difluoro-4-nitrophenyl)-2,5-dihydropyrrole Chemical compound FC1=CC([N+](=O)[O-])=CC(F)=C1N1CC=CC1 JLTWGXIEPHGMSB-UHFFFAOYSA-N 0.000 description 1
• LFNSUPKYOILNNV-UHFFFAOYSA-N 1-(3,5-difluorophenyl)-2,5-dimethylpyrrole Chemical compound CC1=CC=C(C)N1C1=CC(F)=CC(F)=C1 LFNSUPKYOILNNV-UHFFFAOYSA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• SFNVQIUVPJGWOT-UHFFFAOYSA-N 1-[4-(3,6-dihydro-2h-thiopyran-4-yl)-3,5-difluorophenyl]-2,5-dimethylpyrrole Chemical compound CC1=CC=C(C)N1C(C=C1F)=CC(F)=C1C1=CCSCC1 SFNVQIUVPJGWOT-UHFFFAOYSA-N 0.000 description 1
• WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
• BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 1
• KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
• ODUZJBKKYBQIBX-UHFFFAOYSA-N 2,6-difluoroaniline Chemical compound NC1=C(F)C=CC=C1F ODUZJBKKYBQIBX-UHFFFAOYSA-N 0.000 description 1
• AVRQBXVUUXHRMY-UHFFFAOYSA-N 2,6-difluorobenzamide Chemical compound NC(=O)C1=C(F)C=CC=C1F AVRQBXVUUXHRMY-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
• QOZLOYKAFDTQNU-UHFFFAOYSA-N 2-amino-3-fluorophenol Chemical compound NC1=C(O)C=CC=C1F QOZLOYKAFDTQNU-UHFFFAOYSA-N 0.000 description 1
• MMPCQNQNZBGCLH-UHFFFAOYSA-N 2-amino-3-fluorophenol;2-fluoro-6-phenylmethoxyaniline Chemical compound NC1=C(O)C=CC=C1F.NC1=C(F)C=CC=C1OCC1=CC=CC=C1 MMPCQNQNZBGCLH-UHFFFAOYSA-N 0.000 description 1
• REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 1
• 229940013085 2-diethylaminoethanol Drugs 0.000 description 1
• OPEGDEXACXOYKP-UHFFFAOYSA-N 2-fluoro-3-piperazin-1-ylaniline Chemical compound NC1=CC=CC(N2CCNCC2)=C1F OPEGDEXACXOYKP-UHFFFAOYSA-N 0.000 description 1
• MMWFMFZFCKADEL-UHFFFAOYSA-N 2-fluoro-4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1F MMWFMFZFCKADEL-UHFFFAOYSA-N 0.000 description 1
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
• HAFGRUIZARYXRO-UHFFFAOYSA-N 2-methylpropyl n-(3-fluoro-4-iodophenyl)carbamate Chemical compound CC(C)COC(=O)NC1=CC=C(I)C(F)=C1 HAFGRUIZARYXRO-UHFFFAOYSA-N 0.000 description 1
• NGLNAWJEGNSZPA-UHFFFAOYSA-N 2-methylpropyl n-[3-fluoro-4-(4-hydroxythian-4-yl)phenyl]carbamate Chemical compound FC1=CC(NC(=O)OCC(C)C)=CC=C1C1(O)CCSCC1 NGLNAWJEGNSZPA-UHFFFAOYSA-N 0.000 description 1
• FNBRWWLGSBMWKP-UHFFFAOYSA-N 2-methylpropyl n-[4-(1,1-dioxo-1,4-thiazinan-4-yl)-3,5-difluorophenyl]carbamate Chemical compound FC1=CC(NC(=O)OCC(C)C)=CC(F)=C1N1CCS(=O)(=O)CC1 FNBRWWLGSBMWKP-UHFFFAOYSA-N 0.000 description 1
• OWLXTOJXSFWXIN-UHFFFAOYSA-N 2-methylpropyl n-[4-(1,1-dioxothian-4-yl)-3-fluorophenyl]carbamate Chemical compound FC1=CC(NC(=O)OCC(C)C)=CC=C1C1CCS(=O)(=O)CC1 OWLXTOJXSFWXIN-UHFFFAOYSA-N 0.000 description 1
• FJSBTVAXYCIQBF-UHFFFAOYSA-N 2-methylpropyl n-[4-(4-hydroxythian-4-yl)phenyl]carbamate Chemical group C1=CC(NC(=O)OCC(C)C)=CC=C1C1(O)CCSCC1 FJSBTVAXYCIQBF-UHFFFAOYSA-N 0.000 description 1
• PKZCRWFNSBIBEW-UHFFFAOYSA-N 2-n,2-n,2-trimethylpropane-1,2-diamine Chemical compound CN(C)C(C)(C)CN PKZCRWFNSBIBEW-UHFFFAOYSA-N 0.000 description 1
• SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
• LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
• NSXKHUFNJWKZRI-UHFFFAOYSA-N 2H-thiopyran-4-yl N-phenylcarbamate Chemical compound S1CC=C(C=C1)OC(NC1=CC=CC=C1)=O NSXKHUFNJWKZRI-UHFFFAOYSA-N 0.000 description 1
• PEVHDVZBCTYSKM-UHFFFAOYSA-N 2h-thiopyran-4-ol Chemical compound OC1=CCSC=C1 PEVHDVZBCTYSKM-UHFFFAOYSA-N 0.000 description 1
• YMMHAIJRFWRDMG-UHFFFAOYSA-N 3,4,4a,5-tetrahydro-1h-quinolin-2-one Chemical compound C1C=CC=C2NC(=O)CCC21 YMMHAIJRFWRDMG-UHFFFAOYSA-N 0.000 description 1
• FLSFZMRKWKUTFM-UHFFFAOYSA-N 3,5-difluoro-4-(thian-4-yl)aniline Chemical compound FC1=CC(N)=CC(F)=C1C1CCSCC1 FLSFZMRKWKUTFM-UHFFFAOYSA-N 0.000 description 1
• YSZMSIBWWSWHEB-UHFFFAOYSA-N 3,5-difluoro-4-morpholin-4-ylaniline Chemical compound FC1=CC(N)=CC(F)=C1N1CCOCC1 YSZMSIBWWSWHEB-UHFFFAOYSA-N 0.000 description 1
• JNVNXBAPAHAIQV-UHFFFAOYSA-N 3,5-difluoro-4-thiomorpholin-4-ylaniline Chemical compound FC1=CC(N)=CC(F)=C1N1CCSCC1 JNVNXBAPAHAIQV-UHFFFAOYSA-N 0.000 description 1
• QXCAHEXKUMUTRF-UHFFFAOYSA-N 3,6-dihydro-2h-pyran-4-yl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CCOCC1 QXCAHEXKUMUTRF-UHFFFAOYSA-N 0.000 description 1
• GTDYKIMZCQLUNT-UHFFFAOYSA-N 3-(3,4-dihydro-2h-pyridin-1-yl)-1,3-oxazolidin-2-one Chemical compound O=C1OCCN1N1C=CCCC1 GTDYKIMZCQLUNT-UHFFFAOYSA-N 0.000 description 1
• UXBLDQMSOWQULB-UHFFFAOYSA-N 3-amino-2-methyl-6,7,8,9-tetrahydro-5h-cyclohepta[2,3]thieno[2,4-d]pyrimidin-4-one Chemical compound C1CCCCC2=C1SC1=C2C(=O)N(N)C(C)=N1 UXBLDQMSOWQULB-UHFFFAOYSA-N 0.000 description 1
• NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
• XWGJVQLPRBNUNS-UHFFFAOYSA-N 3-fluoro-4-thiomorpholin-4-ylaniline Chemical group FC1=CC(N)=CC=C1N1CCSCC1 XWGJVQLPRBNUNS-UHFFFAOYSA-N 0.000 description 1
• QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical compound NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 description 1
• DHXBDZCJKSLIJE-UHFFFAOYSA-N 3-hydroxy-2-oxo-1,3-oxazolidine-5-carboxamide Chemical compound ON1C(OC(C1)C(=O)N)=O DHXBDZCJKSLIJE-UHFFFAOYSA-N 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• KWIVRAVCZJXOQC-UHFFFAOYSA-N 3h-oxathiazole Chemical compound N1SOC=C1 KWIVRAVCZJXOQC-UHFFFAOYSA-N 0.000 description 1
• RAXMVOYLSJCNTN-UHFFFAOYSA-N 4-(2,6-difluoro-4-nitrophenyl)thiomorpholine Chemical compound FC1=CC([N+](=O)[O-])=CC(F)=C1N1CCSCC1 RAXMVOYLSJCNTN-UHFFFAOYSA-N 0.000 description 1
• MHCRLDZZHOVFEE-UHFFFAOYSA-N 4-(4-aminophenyl)morpholin-3-one Chemical compound C1=CC(N)=CC=C1N1C(=O)COCC1 MHCRLDZZHOVFEE-UHFFFAOYSA-N 0.000 description 1
• VTMGMMPHJFAIDX-UHFFFAOYSA-N 4-(5,7-dihydropyrrolo[3,4-b]pyridin-6-yl)-3-fluoroaniline Chemical group FC1=CC(N)=CC=C1N1CC2=NC=CC=C2C1 VTMGMMPHJFAIDX-UHFFFAOYSA-N 0.000 description 1
• FYTRDWNKMKCQSH-UHFFFAOYSA-N 4-[[dimethyl(oxo)-$l^{6}-sulfanylidene]amino]benzonitrile Chemical compound CS(C)(=O)=NC1=CC=C(C#N)C=C1 FYTRDWNKMKCQSH-UHFFFAOYSA-N 0.000 description 1
• VLVCDUSVTXIWGW-UHFFFAOYSA-N 4-iodoaniline Chemical compound NC1=CC=C(I)C=C1 VLVCDUSVTXIWGW-UHFFFAOYSA-N 0.000 description 1
• 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
• KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
• XQIRIYJOVQEBDL-UHFFFAOYSA-N 4h-1,2-benzothiazin-3-one Chemical compound C1=CC=C2SNC(=O)CC2=C1 XQIRIYJOVQEBDL-UHFFFAOYSA-N 0.000 description 1
• GTFMIJNXNMDHAB-UHFFFAOYSA-N 4h-1,4-benzothiazin-3-one Chemical compound C1=CC=C2NC(=O)CSC2=C1 GTFMIJNXNMDHAB-UHFFFAOYSA-N 0.000 description 1
• LSYOFPBORRARMF-UHFFFAOYSA-N 5-(hydroxymethyl)-1,3-oxazolidin-2-one Chemical compound OCC1CNC(=O)O1 LSYOFPBORRARMF-UHFFFAOYSA-N 0.000 description 1
• HUVCQYKPBBODTJ-UHFFFAOYSA-N 5-fluoro-1-[(4-methoxy-3-nitrophenyl)methyl]-3-methylpyrimidine-2,4-dione Chemical compound C1=C([N+]([O-])=O)C(OC)=CC=C1CN1C(=O)N(C)C(=O)C(F)=C1 HUVCQYKPBBODTJ-UHFFFAOYSA-N 0.000 description 1
• CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
• NZXJETHXSNAQGR-UHFFFAOYSA-N 6-amino-3-ethyl-1,3-benzothiazol-2-one Chemical compound C1=C(N)C=C2SC(=O)N(CC)C2=C1 NZXJETHXSNAQGR-UHFFFAOYSA-N 0.000 description 1
• BMTVSYWNEKQCIQ-UHFFFAOYSA-N 6-amino-8-fluoro-1-methyl-3,4-dihydroquinolin-2-one Chemical compound NC1=CC(F)=C2N(C)C(=O)CCC2=C1 BMTVSYWNEKQCIQ-UHFFFAOYSA-N 0.000 description 1
• QLUFBCVWKTWKBF-UHFFFAOYSA-N 6-nitro-1,3-benzothiazole Chemical compound [O-][N+](=O)C1=CC=C2N=CSC2=C1 QLUFBCVWKTWKBF-UHFFFAOYSA-N 0.000 description 1
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
• HSSOKKMHIZSFTR-UHFFFAOYSA-N 8-fluoro-6-(hydroxymethyl)-4h-1,4-benzoxazin-3-one Chemical compound O1CC(=O)NC2=CC(CO)=CC(F)=C21 HSSOKKMHIZSFTR-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000969130 Atthis Species 0.000 description 1
• 241000606125 Bacteroides Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 125000000739 C2-C30 alkenyl group Chemical group 0.000 description 1
• 101150110592 CTS1 gene Proteins 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 241001112696 Clostridia Species 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
• 238000006824 Eschweiler-Clarke methylation reaction Methods 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical class [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 1
• LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• 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
• 241001465754 Metazoa Species 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• 241000187479 Mycobacterium tuberculosis Species 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
• LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
• 150000001204 N-oxides Chemical class 0.000 description 1
• 208000005141 Otitis Diseases 0.000 description 1
• 206010033078 Otitis media Diseases 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 239000004264 Petrolatum Substances 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
• 239000005708 Sodium hypochlorite Substances 0.000 description 1
• 229920002125 Sokalan® Polymers 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• 241000295644 Staphylococcaceae Species 0.000 description 1
• 241000191967 Staphylococcus aureus Species 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 241000748245 Villanova Species 0.000 description 1
• 206010052428 Wound Diseases 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• HPOFDEDYVZNBFK-UHFFFAOYSA-N [1-(2,6-difluoro-4-nitrophenyl)-3,6-dihydro-2h-pyridin-4-yl]oxy-tri(propan-2-yl)silane Chemical compound C1CC(O[Si](C(C)C)(C(C)C)C(C)C)=CCN1C1=C(F)C=C([N+]([O-])=O)C=C1F HPOFDEDYVZNBFK-UHFFFAOYSA-N 0.000 description 1
• GNLJSGIRSIFOOF-UHFFFAOYSA-N [1-(2-fluoro-4-nitrophenyl)-3,6-dihydro-2h-pyridin-4-yl]oxy-trimethylsilane Chemical compound C1CC(O[Si](C)(C)C)=CCN1C1=CC=C([N+]([O-])=O)C=C1F GNLJSGIRSIFOOF-UHFFFAOYSA-N 0.000 description 1
• DCHRPDVNJYUZDC-UHFFFAOYSA-N [1-(4-nitrophenyl)-3,6-dihydro-2h-pyridin-4-yl]oxy-tri(propan-2-yl)silane Chemical compound C1CC(O[Si](C(C)C)(C(C)C)C(C)C)=CCN1C1=CC=C([N+]([O-])=O)C=C1 DCHRPDVNJYUZDC-UHFFFAOYSA-N 0.000 description 1
• DUGMQSKMPOKDNZ-UHFFFAOYSA-N [2-(3,6-dihydro-2h-thiopyran-4-yl)phenyl] carbamate Chemical class NC(=O)OC1=CC=CC=C1C1=CCSCC1 DUGMQSKMPOKDNZ-UHFFFAOYSA-N 0.000 description 1
• GHIKDGYXAICMPH-UHFFFAOYSA-N [2-(4-hydroxythiopyran-4-yl)phenyl] carbamate Chemical compound C(N)(OC1=C(C=CC=C1)C1(C=CSC=C1)O)=O GHIKDGYXAICMPH-UHFFFAOYSA-N 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
• WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 1
• RAFKCLFWELPONH-UHFFFAOYSA-N acetonitrile;dichloromethane Chemical compound CC#N.ClCCl RAFKCLFWELPONH-UHFFFAOYSA-N 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000010933 acylation Effects 0.000 description 1
• 238000005917 acylation reaction Methods 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 230000000996 additive effect Effects 0.000 description 1
• 239000000853 adhesive Substances 0.000 description 1
• 230000001070 adhesive effect Effects 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 239000002168 alkylating agent Substances 0.000 description 1
• 229940100198 alkylating agent Drugs 0.000 description 1
• XNEDWIDPHRYREZ-UHFFFAOYSA-N amino 2-hydroxypropanoate Chemical compound CC(O)C(=O)ON XNEDWIDPHRYREZ-UHFFFAOYSA-N 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 150000001450 anions Chemical class 0.000 description 1
• 238000009635 antibiotic susceptibility testing Methods 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229960003121 arginine Drugs 0.000 description 1
• 150000001502 aryl halides Chemical class 0.000 description 1
• 150000001539 azetidines Chemical class 0.000 description 1
• XIOUCIKZATWNIJ-UHFFFAOYSA-N azii Chemical compound O1C(C)=C(O)C(=O)CC1OC1C2(C)CCC3(C)C4(C)CCC5C(C)(CO)C(OC6C(C(O)C(O)C(O6)C(O)=O)OC6C(C(O)C(O)C(O6)C(O)=O)OC6C(C(O)C(O)C(CO)O6)O)CCC5(C)C4CC=C3C2CC(C)(C)C1 XIOUCIKZATWNIJ-UHFFFAOYSA-N 0.000 description 1
• 150000007514 bases Chemical class 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• DVEIDGKSJOJJJU-UHFFFAOYSA-N benzotriazole-1-carbaldehyde Chemical compound C1=CC=C2N(C=O)N=NC2=C1 DVEIDGKSJOJJJU-UHFFFAOYSA-N 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• DWDZYAWYNKMKDZ-GOSISDBHSA-N benzyl (2r)-2-methyl-5-(phenylmethoxycarbonylamino)-2,3-dihydroindole-1-carboxylate Chemical compound C([C@H](N(C1=CC=2)C(=O)OCC=3C=CC=CC=3)C)C1=CC=2NC(=O)OCC1=CC=CC=C1 DWDZYAWYNKMKDZ-GOSISDBHSA-N 0.000 description 1
• OPWCRBOOVRSYHY-UHFFFAOYSA-N benzyl 4-[2-fluoro-4-(phenylmethoxycarbonylamino)phenyl]piperazine-1-carboxylate Chemical compound C=1C=C(N2CCN(CC2)C(=O)OCC=2C=CC=CC=2)C(F)=CC=1NC(=O)OCC1=CC=CC=C1 OPWCRBOOVRSYHY-UHFFFAOYSA-N 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
• MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
• 229960003237 betaine Drugs 0.000 description 1
• 239000012455 biphasic mixture Substances 0.000 description 1
• YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
• 230000036765 blood level Effects 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• PDIRPVPNNLOAKW-ZCFIWIBFSA-N butyl (2r)-oxirane-2-carboxylate Chemical compound CCCCOC(=O)[C@H]1CO1 PDIRPVPNNLOAKW-ZCFIWIBFSA-N 0.000 description 1
• JGEHYDYWPNRITN-OAHLLOKOSA-N butyl (5r)-2-oxo-3-(2-oxo-3-propan-2-yl-1,3-benzoxazol-6-yl)-1,3-oxazolidine-5-carboxylate Chemical group O=C1O[C@@H](C(=O)OCCCC)CN1C1=CC=C(N(C(C)C)C(=O)O2)C2=C1 JGEHYDYWPNRITN-OAHLLOKOSA-N 0.000 description 1
• AUIBPQAPVHZGRI-OAHLLOKOSA-N butyl (5r)-3-(3,5-difluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OCCCC)CN1C(C=C1F)=CC(F)=C1N1CCOCC1 AUIBPQAPVHZGRI-OAHLLOKOSA-N 0.000 description 1
• BCYXRYBHWQWIEP-OAHLLOKOSA-N butyl (5r)-3-(3,5-difluoro-4-thiomorpholin-4-ylphenyl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical group O=C1O[C@@H](C(=O)OCCCC)CN1C(C=C1F)=CC(F)=C1N1CCSCC1 BCYXRYBHWQWIEP-OAHLLOKOSA-N 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 229960001948 caffeine Drugs 0.000 description 1
• VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
• 150000001669 calcium Chemical class 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 150000001718 carbodiimides Chemical class 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 239000006285 cell suspension Substances 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 150000005829 chemical entities Chemical class 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 229960004926 chlorobutanol Drugs 0.000 description 1
• QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
• ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
• NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
• UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
• VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
• KNKSUPJXMOAWAC-UHFFFAOYSA-N dipropan-2-yl 2,6-dimethyl-4-thiophen-2-yl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CC(C)OC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CS1 KNKSUPJXMOAWAC-UHFFFAOYSA-N 0.000 description 1
• 229940042397 direct acting antivirals cyclic amines Drugs 0.000 description 1
• 201000010099 disease Diseases 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002270 dispersing agent Substances 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 239000012153 distilled water Substances 0.000 description 1
• AFOSIXZFDONLBT-UHFFFAOYSA-N divinyl sulfone Chemical compound C=CS(=O)(=O)C=C AFOSIXZFDONLBT-UHFFFAOYSA-N 0.000 description 1
• 239000000975 dye Substances 0.000 description 1
• 208000019258 ear infection Diseases 0.000 description 1
• 210000005069 ears Anatomy 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 230000002255 enzymatic effect Effects 0.000 description 1
• JKMBMIMLVFMXRW-LYYFRFARSA-N epicocconone Chemical compound C1=C2C[C@@H](CO)OC=C2C(=O)[C@]2(C)C1=C(C(/O)=C/C(=O)/C=C/C=C/C=C/C)C(=O)O2 JKMBMIMLVFMXRW-LYYFRFARSA-N 0.000 description 1
• VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 239000012259 ether extract Substances 0.000 description 1
• KQCBSWBQAXTILK-WYMLVPIESA-N ethyl (1e)-n-(2,4,6-trimethylphenyl)sulfonyloxyethanimidate Chemical compound CCO\C(C)=N\OS(=O)(=O)C1=C(C)C=C(C)C=C1C KQCBSWBQAXTILK-WYMLVPIESA-N 0.000 description 1
• MIHRVXYXORIINI-UHFFFAOYSA-N ethyl 2-cyanopropionate Chemical compound CCOC(=O)C(C)C#N MIHRVXYXORIINI-UHFFFAOYSA-N 0.000 description 1
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 239000012467 final product Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 230000037406 food intake Effects 0.000 description 1
• 239000003205 fragrance Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 238000005227 gel permeation chromatography Methods 0.000 description 1
• 238000007429 general method Methods 0.000 description 1
• 239000011521 glass Substances 0.000 description 1
• 229960002442 glucosamine Drugs 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 125000005908 glyceryl ester group Chemical group 0.000 description 1
• 239000001087 glyceryl triacetate Substances 0.000 description 1
• 235000013773 glyceryl triacetate Nutrition 0.000 description 1
• 238000005469 granulation Methods 0.000 description 1
• 230000003179 granulation Effects 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 238000007074 heterocyclization reaction Methods 0.000 description 1
• XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
• 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 239000007943 implant Substances 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 208000022760 infectious otitis media Diseases 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 238000011221 initial treatment Methods 0.000 description 1
• 239000007972 injectable composition Substances 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 239000004922 lacquer Substances 0.000 description 1
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 125000005905 mesyloxy group Chemical group 0.000 description 1
• 238000006263 metalation reaction Methods 0.000 description 1
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
• KPGDKTQFCZJXLD-SNVBAGLBSA-N methyl (2r)-3-[(4-fluoro-2-oxo-3-propan-2-yl-1,3-benzoxazol-6-yl)amino]-2-hydroxypropanoate Chemical compound COC(=O)[C@H](O)CNC1=CC(F)=C2N(C(C)C)C(=O)OC2=C1 KPGDKTQFCZJXLD-SNVBAGLBSA-N 0.000 description 1
• DCZQCTOHELSBSJ-MRVPVSSYSA-N methyl (2r)-3-[(4-fluoro-3-methyl-2-oxo-1,3-benzoxazol-6-yl)amino]-2-hydroxypropanoate Chemical compound COC(=O)[C@H](O)CNC1=CC(F)=C2N(C)C(=O)OC2=C1 DCZQCTOHELSBSJ-MRVPVSSYSA-N 0.000 description 1
• LKGWFJDOOXJXHT-GFCCVEGCSA-N methyl (2r)-3-[4-(2,5-dihydropyrrol-1-yl)-3,5-difluoroanilino]-2-hydroxypropanoate Chemical compound FC1=CC(NC[C@@H](O)C(=O)OC)=CC(F)=C1N1CC=CC1 LKGWFJDOOXJXHT-GFCCVEGCSA-N 0.000 description 1
• YQOUCAHIJZXFCR-LLVKDONJSA-N methyl (5r)-3-(4-fluoro-2-oxo-3-propan-2-yl-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C1=CC(F)=C(N(C(C)C)C(=O)O2)C2=C1 YQOUCAHIJZXFCR-LLVKDONJSA-N 0.000 description 1
• PFQHLCKOLVURAI-SECBINFHSA-N methyl (5r)-3-(4-fluoro-3-methyl-2-oxo-1,3-benzoxazol-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C1=CC(F)=C(N(C)C(=O)O2)C2=C1 PFQHLCKOLVURAI-SECBINFHSA-N 0.000 description 1
• IGZKWZIWBNPUAS-HXUWFJFHSA-N methyl (5r)-3-[3-fluoro-4-(4-phenylmethoxycarbonylpiperazin-1-yl)phenyl]-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1O[C@@H](C(=O)OC)CN1C(C=C1F)=CC=C1N1CCN(C(=O)OCC=2C=CC=CC=2)CC1 IGZKWZIWBNPUAS-HXUWFJFHSA-N 0.000 description 1
• YOAIRDDVWDKCTO-UHFFFAOYSA-N methyl 2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound COC(=O)C1CNC(=O)O1 YOAIRDDVWDKCTO-UHFFFAOYSA-N 0.000 description 1
• AHBKOHHLMLEPEM-UHFFFAOYSA-N methyl 3-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1OC(C(=O)OC)CN1C1=CC=C(N(C)C(=O)CC2)C2=C1 AHBKOHHLMLEPEM-UHFFFAOYSA-N 0.000 description 1
• KIQHJYWZNVFGCC-UHFFFAOYSA-N methyl 3-(8-fluoro-1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-2-oxo-1,3-oxazolidine-5-carboxylate Chemical compound O=C1OC(C(=O)OC)CN1C1=CC(F)=C(N(C)C(=O)CC2)C2=C1 KIQHJYWZNVFGCC-UHFFFAOYSA-N 0.000 description 1
• XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
• YHLVIDQQTOMBGN-UHFFFAOYSA-N methyl prop-2-enyl carbonate Chemical compound COC(=O)OCC=C YHLVIDQQTOMBGN-UHFFFAOYSA-N 0.000 description 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N mono-n-propyl amine Natural products CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 150000004682 monohydrates Chemical class 0.000 description 1
• 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
• 235000019799 monosodium phosphate Nutrition 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
• BXGTVNLGPMZLAZ-UHFFFAOYSA-N n'-ethylmethanediimine;hydrochloride Chemical compound Cl.CCN=C=N BXGTVNLGPMZLAZ-UHFFFAOYSA-N 0.000 description 1
• OEXMNSOPAKOPEF-UHFFFAOYSA-N n-[4-[(4-acetamidophenyl)methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CC1=CC=C(NC(C)=O)C=C1 OEXMNSOPAKOPEF-UHFFFAOYSA-N 0.000 description 1
• QQSRDPPYXVPRHQ-UHFFFAOYSA-N n-phenylazetidin-1-amine Chemical compound C1CCN1NC1=CC=CC=C1 QQSRDPPYXVPRHQ-UHFFFAOYSA-N 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 150000005181 nitrobenzenes Chemical class 0.000 description 1
• 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
• HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical group Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 229940060184 oil ingredients Drugs 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• DBSMLQTUDJVICQ-CJODITQLSA-N onametostat Chemical compound NC1=C2C=CN([C@@H]3C[C@H](CCC4=CC=C5C=C(Br)C(N)=NC5=C4)[C@@H](O)[C@H]3O)C2=NC=N1 DBSMLQTUDJVICQ-CJODITQLSA-N 0.000 description 1
• 239000003791 organic solvent mixture Substances 0.000 description 1
• 229910052762 osmium Inorganic materials 0.000 description 1
• SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 1
• 239000012285 osmium tetroxide Substances 0.000 description 1
• 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
• 125000003431 oxalo group Chemical group 0.000 description 1
• 125000005880 oxathiolanyl group Chemical group 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• YLNSNVGRSIOCEU-UHFFFAOYSA-N oxiran-2-ylmethyl butanoate Chemical compound CCCC(=O)OCC1CO1 YLNSNVGRSIOCEU-UHFFFAOYSA-N 0.000 description 1
• 150000002924 oxiranes Chemical class 0.000 description 1
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 229940066842 petrolatum Drugs 0.000 description 1
• DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical class NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
• 239000000049 pigment Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 229910003446 platinum oxide Inorganic materials 0.000 description 1
• 239000003880 polar aprotic solvent Substances 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229920000768 polyamine Polymers 0.000 description 1
• 239000008389 polyethoxylated castor oil Substances 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
• 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
• 229920000137 polyphosphoric acid Polymers 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229940113124 polysorbate 60 Drugs 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 150000003141 primary amines Chemical class 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
• 238000012545 processing Methods 0.000 description 1
• 125000006308 propyl amino group Chemical group 0.000 description 1
• 230000029983 protein stabilization Effects 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
• DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• GHBFNMLVSPCDGN-UHFFFAOYSA-N rac-1-monooctanoylglycerol Chemical compound CCCCCCCC(=O)OCC(O)CO GHBFNMLVSPCDGN-UHFFFAOYSA-N 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 210000000664 rectum Anatomy 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 150000003335 secondary amines Chemical class 0.000 description 1
• 235000010413 sodium alginate Nutrition 0.000 description 1
• 239000000661 sodium alginate Substances 0.000 description 1
• 229940005550 sodium alginate Drugs 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000001509 sodium citrate Substances 0.000 description 1
• NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
• AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
• BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 1
• SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• 239000008247 solid mixture Substances 0.000 description 1
• 239000011877 solvent mixture Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000001587 sorbitan monostearate Substances 0.000 description 1
• 235000011076 sorbitan monostearate Nutrition 0.000 description 1
• 229940035048 sorbitan monostearate Drugs 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 238000001694 spray drying Methods 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 229910000080 stannane Inorganic materials 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 238000000967 suction filtration Methods 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 125000004354 sulfur functional group Chemical group 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 229940066769 systemic antihistamines substituted alkylamines Drugs 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• RWYCEPAZXUIYSN-UHFFFAOYSA-N tert-butyl n-[(2-fluoro-4-nitrobenzoyl)amino]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)C1=CC=C([N+]([O-])=O)C=C1F RWYCEPAZXUIYSN-UHFFFAOYSA-N 0.000 description 1
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
• DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
• 150000003512 tertiary amines Chemical class 0.000 description 1
• 238000010998 test method Methods 0.000 description 1
• 238000012956 testing procedure Methods 0.000 description 1
• UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
• MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
• DGQOCLATAPFASR-UHFFFAOYSA-N tetrahydroxy-1,4-benzoquinone Chemical compound OC1=C(O)C(=O)C(O)=C(O)C1=O DGQOCLATAPFASR-UHFFFAOYSA-N 0.000 description 1
• 229960004559 theobromine Drugs 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• YGNGABUJMXJPIJ-UHFFFAOYSA-N thiatriazole Chemical compound C1=NN=NS1 YGNGABUJMXJPIJ-UHFFFAOYSA-N 0.000 description 1
• RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
• 229940033663 thimerosal Drugs 0.000 description 1
• 125000005505 thiomorpholino group Chemical group 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 235000010215 titanium dioxide Nutrition 0.000 description 1
• 229960005196 titanium dioxide Drugs 0.000 description 1
• 230000037317 transdermal delivery Effects 0.000 description 1
• 229960002622 triacetin Drugs 0.000 description 1
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
• YCBWXJZXFUKDPU-UHFFFAOYSA-N trimethyl(pyridin-4-yl)stannane Chemical group C[Sn](C)(C)C1=CC=NC=C1 YCBWXJZXFUKDPU-UHFFFAOYSA-N 0.000 description 1
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
• YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• 238000001291 vacuum drying Methods 0.000 description 1
• 239000012808 vapor phase Substances 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 229940124024 weight reducing agent Drugs 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1