JP2022535613A - 新規なアミノアルカン酸にビフェニル基を導入した誘導体化合物、およびこれを含む抗真菌薬学的組成物 - Google Patents
新規なアミノアルカン酸にビフェニル基を導入した誘導体化合物、およびこれを含む抗真菌薬学的組成物 Download PDFInfo
- Publication number
- JP2022535613A JP2022535613A JP2021577309A JP2021577309A JP2022535613A JP 2022535613 A JP2022535613 A JP 2022535613A JP 2021577309 A JP2021577309 A JP 2021577309A JP 2021577309 A JP2021577309 A JP 2021577309A JP 2022535613 A JP2022535613 A JP 2022535613A
- Authority
- JP
- Japan
- Prior art keywords
- biphenyl
- compound
- amino
- mmol
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 145
- 239000002253 acid Substances 0.000 title claims abstract description 32
- 230000000843 anti-fungal effect Effects 0.000 title claims abstract description 22
- 229940121375 antifungal agent Drugs 0.000 title claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 18
- 125000006267 biphenyl group Chemical group 0.000 title abstract description 16
- -1 proline amino acids Chemical class 0.000 claims abstract description 106
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- 239000000203 mixture Substances 0.000 claims abstract description 24
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 120
- 238000004519 manufacturing process Methods 0.000 claims description 89
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 51
- 238000006243 chemical reaction Methods 0.000 claims description 41
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 claims description 40
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 37
- 239000000126 substance Substances 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 241000894006 Bacteria Species 0.000 claims description 13
- 241000222122 Candida albicans Species 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 241000221204 Cryptococcus neoformans Species 0.000 claims description 12
- 206010017533 Fungal infection Diseases 0.000 claims description 12
- 208000031888 Mycoses Diseases 0.000 claims description 12
- 229940095731 candida albicans Drugs 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 201000007336 Cryptococcosis Diseases 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 239000003429 antifungal agent Substances 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 6
- 241000222126 [Candida] glabrata Species 0.000 claims description 6
- 208000032343 candida glabrata infection Diseases 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 6
- 238000005804 alkylation reaction Methods 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 230000000844 anti-bacterial effect Effects 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 230000002538 fungal effect Effects 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 150000003141 primary amines Chemical group 0.000 claims description 5
- 241001225321 Aspergillus fumigatus Species 0.000 claims description 4
- 230000029936 alkylation Effects 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 239000012871 anti-fungal composition Substances 0.000 claims description 4
- 229940091771 aspergillus fumigatus Drugs 0.000 claims description 4
- 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 150000001350 alkyl halides Chemical class 0.000 claims description 3
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- CRLGUHCBJCSGRN-UHFFFAOYSA-N 2-(methylamino)-N-[2-[4-[4-(trifluoromethoxy)phenyl]phenyl]ethyl]butanamide Chemical compound CCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC CRLGUHCBJCSGRN-UHFFFAOYSA-N 0.000 claims description 2
- LRNQSIAZLRCDLJ-UHFFFAOYSA-N 2-(methylamino)-N-[2-[4-[4-(trifluoromethoxy)phenyl]phenyl]ethyl]hexanamide Chemical compound CCCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC LRNQSIAZLRCDLJ-UHFFFAOYSA-N 0.000 claims description 2
- RXIFVDZHQGZVLK-UHFFFAOYSA-N 2-(methylamino)-N-[2-[4-[4-(trifluoromethoxy)phenyl]phenyl]ethyl]pentanamide Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC RXIFVDZHQGZVLK-UHFFFAOYSA-N 0.000 claims description 2
- VEXJSYLJHAIHKE-UHFFFAOYSA-N 2-(methylamino)-N-[2-[4-[4-(trifluoromethyl)phenyl]phenyl]ethyl]butanamide Chemical compound CCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC VEXJSYLJHAIHKE-UHFFFAOYSA-N 0.000 claims description 2
- YVBXRUORJSHAHW-UHFFFAOYSA-N 2-(methylamino)-N-[2-[4-[4-(trifluoromethyl)phenyl]phenyl]ethyl]hexanamide Chemical compound CCCCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC YVBXRUORJSHAHW-UHFFFAOYSA-N 0.000 claims description 2
- FOSSAORQPWZMJL-UHFFFAOYSA-N 2-(methylamino)-N-[2-[4-[4-(trifluoromethyl)phenyl]phenyl]ethyl]pentanamide Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC FOSSAORQPWZMJL-UHFFFAOYSA-N 0.000 claims description 2
- PXXDTPAZZJKZBN-UHFFFAOYSA-N 2-(methylamino)-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]pentanamide Chemical compound CCCC(C(NCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC PXXDTPAZZJKZBN-UHFFFAOYSA-N 0.000 claims description 2
- JXDHNFMEEYIHIW-UHFFFAOYSA-N 2-amino-N-[2-[4-(3,4-dichlorophenyl)phenyl]ethyl]butanamide Chemical compound CCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N JXDHNFMEEYIHIW-UHFFFAOYSA-N 0.000 claims description 2
- HAOFODZMSVSQRH-UHFFFAOYSA-N 2-amino-N-[2-[4-(3,4-dichlorophenyl)phenyl]ethyl]hexanamide Chemical compound CCCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N HAOFODZMSVSQRH-UHFFFAOYSA-N 0.000 claims description 2
- GQYPNMGFRGWEPG-UHFFFAOYSA-N 2-amino-N-[2-[4-(3,4-dichlorophenyl)phenyl]ethyl]pentanamide Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N GQYPNMGFRGWEPG-UHFFFAOYSA-N 0.000 claims description 2
- MUJGYCPFIPMXHN-UHFFFAOYSA-N 2-amino-N-[2-[4-(3,4-difluorophenyl)phenyl]ethyl]pentanamide Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC(F)=C1F)=O)N MUJGYCPFIPMXHN-UHFFFAOYSA-N 0.000 claims description 2
- JYGGDGASJNFZRL-UHFFFAOYSA-N 2-amino-N-[2-[4-[4-(trifluoromethoxy)phenyl]phenyl]ethyl]butanamide Chemical compound CCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)N JYGGDGASJNFZRL-UHFFFAOYSA-N 0.000 claims description 2
- DFSBMEMSPFPCPE-UHFFFAOYSA-N 2-amino-N-[2-[4-[4-(trifluoromethoxy)phenyl]phenyl]ethyl]hexanamide Chemical compound CCCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)N DFSBMEMSPFPCPE-UHFFFAOYSA-N 0.000 claims description 2
- RAEKLYPZDIFSBT-UHFFFAOYSA-N 2-amino-N-[2-[4-[4-(trifluoromethoxy)phenyl]phenyl]ethyl]pentanamide Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)N RAEKLYPZDIFSBT-UHFFFAOYSA-N 0.000 claims description 2
- CPPUQCIHMRYAJV-UHFFFAOYSA-N 2-amino-N-[2-[4-[4-(trifluoromethyl)phenyl]phenyl]ethyl]butanamide Chemical compound CCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)N CPPUQCIHMRYAJV-UHFFFAOYSA-N 0.000 claims description 2
- FBJWRXBECXKOBG-UHFFFAOYSA-N 2-amino-N-[2-[4-[4-(trifluoromethyl)phenyl]phenyl]ethyl]hexanamide Chemical compound CCCCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)N FBJWRXBECXKOBG-UHFFFAOYSA-N 0.000 claims description 2
- IUKBPXLIJCRMFG-UHFFFAOYSA-N 2-amino-N-[2-[4-[4-(trifluoromethyl)phenyl]phenyl]ethyl]pentanamide Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)N IUKBPXLIJCRMFG-UHFFFAOYSA-N 0.000 claims description 2
- ZCOHZJYWKQFRRS-UHFFFAOYSA-N 2-amino-N-[4-(3,4-dichlorophenyl)phenyl]butanamide Chemical compound CCC(C(NC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N ZCOHZJYWKQFRRS-UHFFFAOYSA-N 0.000 claims description 2
- HRXPHCJHEMJCLV-UHFFFAOYSA-N 2-amino-N-[4-(3,4-dichlorophenyl)phenyl]hexanamide Chemical compound CCCCC(C(NC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N HRXPHCJHEMJCLV-UHFFFAOYSA-N 0.000 claims description 2
- LQGSOCXMUDMTGR-UHFFFAOYSA-N 2-amino-N-[4-(3,4-dichlorophenyl)phenyl]pentanamide Chemical compound CCCC(C(NC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N LQGSOCXMUDMTGR-UHFFFAOYSA-N 0.000 claims description 2
- YHSGYWSVHZHXPV-UHFFFAOYSA-N 2-amino-N-[4-[4-(trifluoromethoxy)phenyl]phenyl]pentanamide Chemical compound CCCC(C(NC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)N YHSGYWSVHZHXPV-UHFFFAOYSA-N 0.000 claims description 2
- FVDKBUAKGQDDHJ-UHFFFAOYSA-N 2-amino-N-[[4-(3,4-dichlorophenyl)phenyl]methyl]hexanamide Chemical compound CCCCC(C(NCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N FVDKBUAKGQDDHJ-UHFFFAOYSA-N 0.000 claims description 2
- LZCFJMKKWFPROR-UHFFFAOYSA-N 2-amino-N-[[4-(3,4-dichlorophenyl)phenyl]methyl]pentanamide Chemical compound CCCC(C(NCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N LZCFJMKKWFPROR-UHFFFAOYSA-N 0.000 claims description 2
- CQNTWNGCUQWBLQ-UHFFFAOYSA-N 2-amino-N-[[4-[4-(trifluoromethoxy)phenyl]phenyl]methyl]hexanamide Chemical compound CCCCC(C(NCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)N CQNTWNGCUQWBLQ-UHFFFAOYSA-N 0.000 claims description 2
- QQZRXXCSMLYFJL-UHFFFAOYSA-N 2-amino-N-[[4-[4-(trifluoromethoxy)phenyl]phenyl]methyl]pentanamide Chemical compound CCCC(C(NCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)N QQZRXXCSMLYFJL-UHFFFAOYSA-N 0.000 claims description 2
- MEDREMNQTMRUFJ-UHFFFAOYSA-N 2-amino-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]hexanamide Chemical compound CCCCC(C(NCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)N MEDREMNQTMRUFJ-UHFFFAOYSA-N 0.000 claims description 2
- HIXYRUVJLXABNQ-UHFFFAOYSA-N 2-amino-N-[[4-[4-(trifluoromethyl)phenyl]phenyl]methyl]pentanamide Chemical compound CCCC(C(NCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)N HIXYRUVJLXABNQ-UHFFFAOYSA-N 0.000 claims description 2
- MTGWORVOKHRVFZ-UHFFFAOYSA-N N-[2-[4-(3,4-dichlorophenyl)phenyl]ethyl]-2-(dimethylamino)pentanamide Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N(C)C MTGWORVOKHRVFZ-UHFFFAOYSA-N 0.000 claims description 2
- CUKWKCARRSCQNU-UHFFFAOYSA-N N-[2-[4-(3,4-dichlorophenyl)phenyl]ethyl]-2-(methylamino)butanamide Chemical compound CCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)NC CUKWKCARRSCQNU-UHFFFAOYSA-N 0.000 claims description 2
- MWHOVMJACDCFAL-UHFFFAOYSA-N N-[2-[4-(3,4-dichlorophenyl)phenyl]ethyl]-2-(methylamino)hexanamide Chemical compound CCCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)NC MWHOVMJACDCFAL-UHFFFAOYSA-N 0.000 claims description 2
- AZWBFVJPSWSDDC-UHFFFAOYSA-N N-[2-[4-(3,4-dichlorophenyl)phenyl]ethyl]-2-(methylamino)pentanamide Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)NC AZWBFVJPSWSDDC-UHFFFAOYSA-N 0.000 claims description 2
- WLNHAQGMSYCBOL-UHFFFAOYSA-N N-[4-(3,4-dichlorophenyl)phenyl]-2-(dimethylamino)pentanamide Chemical compound CCCC(C(NC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N(C)C WLNHAQGMSYCBOL-UHFFFAOYSA-N 0.000 claims description 2
- STTLYDACOOQGRI-UHFFFAOYSA-N N-[4-(3,4-dichlorophenyl)phenyl]-2-(methylamino)butanamide Chemical compound CCC(C(NC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)NC STTLYDACOOQGRI-UHFFFAOYSA-N 0.000 claims description 2
- AGCDZQDCKFLDKP-UHFFFAOYSA-N N-[4-(3,4-dichlorophenyl)phenyl]-2-(methylamino)hexanamide Chemical compound CCCCC(C(NC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)NC AGCDZQDCKFLDKP-UHFFFAOYSA-N 0.000 claims description 2
- YFWURMMFRUBTBF-UHFFFAOYSA-N N-[4-(3,4-dichlorophenyl)phenyl]-2-(methylamino)pentanamide Chemical compound CCCC(C(NC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)NC YFWURMMFRUBTBF-UHFFFAOYSA-N 0.000 claims description 2
- GWDVKTLQOQCYAM-UHFFFAOYSA-N N-[[4-(3,4-dichlorophenyl)phenyl]methyl]-2-(dimethylamino)pentanamide Chemical compound CCCC(C(NCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)N(C)C GWDVKTLQOQCYAM-UHFFFAOYSA-N 0.000 claims description 2
- SUAIKLMVGARJLA-UHFFFAOYSA-N N-[[4-(3,4-dichlorophenyl)phenyl]methyl]-2-(methylamino)pentanamide Chemical compound CCCC(C(NCC(C=C1)=CC=C1C(C=C1)=CC(Cl)=C1Cl)=O)NC SUAIKLMVGARJLA-UHFFFAOYSA-N 0.000 claims description 2
- 150000003973 alkyl amines Chemical class 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 150000008064 anhydrides Chemical class 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 238000006880 cross-coupling reaction Methods 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000005059 halophenyl group Chemical group 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 150000003335 secondary amines Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 3
- 230000000845 anti-microbial effect Effects 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 208000035143 Bacterial infection Diseases 0.000 claims 1
- 241000192125 Firmicutes Species 0.000 claims 1
- 150000003862 amino acid derivatives Chemical class 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- 208000022362 bacterial infectious disease Diseases 0.000 claims 1
- 208000024386 fungal infectious disease Diseases 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 108
- 230000000694 effects Effects 0.000 abstract description 16
- 241000233866 Fungi Species 0.000 abstract description 10
- 238000011282 treatment Methods 0.000 abstract description 9
- 239000012453 solvate Substances 0.000 abstract description 8
- 230000000855 fungicidal effect Effects 0.000 abstract description 6
- 235000001014 amino acid Nutrition 0.000 abstract description 5
- 238000009472 formulation Methods 0.000 abstract description 5
- 241001465754 Metazoa Species 0.000 abstract description 3
- 150000007513 acids Chemical class 0.000 abstract description 3
- 230000002195 synergetic effect Effects 0.000 abstract description 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 abstract 1
- 150000001295 alanines Chemical class 0.000 abstract 1
- 230000003032 phytopathogenic effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 129
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 112
- 238000005481 NMR spectroscopy Methods 0.000 description 85
- 235000019439 ethyl acetate Nutrition 0.000 description 84
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 79
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 48
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 43
- 229910052799 carbon Inorganic materials 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000003814 drug Substances 0.000 description 30
- 239000000843 powder Substances 0.000 description 26
- 229940079593 drug Drugs 0.000 description 25
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 25
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
- HLEKYJVHEBHTMR-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O.CCCCC(N)=O HLEKYJVHEBHTMR-UHFFFAOYSA-N 0.000 description 22
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 21
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 17
- UCMFXAIFSBSDAQ-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O.CCCCCC(N)=O UCMFXAIFSBSDAQ-UHFFFAOYSA-N 0.000 description 16
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 15
- ZIOCIQJXEKFHJO-QMMMGPOBSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CCCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C ZIOCIQJXEKFHJO-QMMMGPOBSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 229940125898 compound 5 Drugs 0.000 description 11
- PNFVIPIQXAIUAY-LURJTMIESA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC[C@@H](C(O)=O)NC(=O)OC(C)(C)C PNFVIPIQXAIUAY-LURJTMIESA-N 0.000 description 10
- QIXDRLIEARGEQY-ZETCQYMHSA-N (2s)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoic acid Chemical compound CC[C@@H](C(O)=O)N(C)C(=O)OC(C)(C)C QIXDRLIEARGEQY-ZETCQYMHSA-N 0.000 description 10
- BSMXBPUTGXWAGA-QMMMGPOBSA-N (2s)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]pentanoic acid Chemical compound CCC[C@@H](C(O)=O)N(C)C(=O)OC(C)(C)C BSMXBPUTGXWAGA-QMMMGPOBSA-N 0.000 description 10
- XZOWIJDBQIHMFC-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O.CCCC(N)=O XZOWIJDBQIHMFC-UHFFFAOYSA-N 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- HYGQYTQHPSQSFF-VIFPVBQESA-N (2s)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]hexanoic acid Chemical compound CCCC[C@@H](C(O)=O)N(C)C(=O)OC(C)(C)C HYGQYTQHPSQSFF-VIFPVBQESA-N 0.000 description 8
- QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 7
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 7
- 229940125810 compound 20 Drugs 0.000 description 7
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 6
- SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 6
- 229960003942 amphotericin b Drugs 0.000 description 6
- 229910052751 metal Inorganic materials 0.000 description 6
- 239000002184 metal Substances 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 5
- INWOAUUPYIXDHN-ZETCQYMHSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C INWOAUUPYIXDHN-ZETCQYMHSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 102000004889 Interleukin-6 Human genes 0.000 description 5
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 229940125797 compound 12 Drugs 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 229940100601 interleukin-6 Drugs 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 229940124597 therapeutic agent Drugs 0.000 description 5
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 4
- JKIGHOARKAIPJI-UHFFFAOYSA-N (3,4-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C(Cl)=C1 JKIGHOARKAIPJI-UHFFFAOYSA-N 0.000 description 4
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 4
- KIMDFENPKUEOLV-UHFFFAOYSA-N 2-[4-(3,4-difluorophenyl)phenyl]ethanamine hydrochloride Chemical compound C1=CC(=CC=C1CCN)C2=CC(=C(C=C2)F)F.Cl KIMDFENPKUEOLV-UHFFFAOYSA-N 0.000 description 4
- NLYNBEAPOWLUTE-UHFFFAOYSA-N 2-[4-[4-(trifluoromethoxy)phenyl]phenyl]ethanamine hydrochloride Chemical compound C1=CC(=CC=C1CCN)C2=CC=C(C=C2)OC(F)(F)F.Cl NLYNBEAPOWLUTE-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- MNJDXYKTFCPFLX-UHFFFAOYSA-N C1=CC(=CC=C1CCN)C2=CC=C(C=C2)C(F)(F)F.Cl Chemical compound C1=CC(=CC=C1CCN)C2=CC=C(C=C2)C(F)(F)F.Cl MNJDXYKTFCPFLX-UHFFFAOYSA-N 0.000 description 4
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 4
- QWCKQJZIFLGMSD-VKHMYHEASA-N L-alpha-aminobutyric acid Chemical compound CC[C@H](N)C(O)=O QWCKQJZIFLGMSD-VKHMYHEASA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- NRDYUXUKFMIWAG-UHFFFAOYSA-N [4-[4-(trifluoromethoxy)phenyl]phenyl]methanamine;hydrochloride Chemical compound Cl.C1=CC(CN)=CC=C1C1=CC=C(OC(F)(F)F)C=C1 NRDYUXUKFMIWAG-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003125 aqueous solvent Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229940125758 compound 15 Drugs 0.000 description 4
- 229940126142 compound 16 Drugs 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 201000002491 encephalomyelitis Diseases 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 230000002458 infectious effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 4
- 229960002722 terbinafine Drugs 0.000 description 4
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 3
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 3
- WJWNUUZNRPTPRN-UHFFFAOYSA-N 2-[4-(3,4-dichlorophenyl)phenyl]ethanamine hydrochloride Chemical compound C1=CC(=CC=C1CCN)C2=CC(=C(C=C2)Cl)Cl.Cl WJWNUUZNRPTPRN-UHFFFAOYSA-N 0.000 description 3
- HPXYLUMQEJUXLN-UHFFFAOYSA-N 4-(3,4-dichlorophenyl)aniline;hydrochloride Chemical compound Cl.C1=CC(N)=CC=C1C1=CC=C(Cl)C(Cl)=C1 HPXYLUMQEJUXLN-UHFFFAOYSA-N 0.000 description 3
- UNPGEDRKQMWGQG-UHFFFAOYSA-N 4-[4-(trifluoromethoxy)phenyl]aniline;hydrochloride Chemical compound Cl.C1=CC(N)=CC=C1C1=CC=C(OC(F)(F)F)C=C1 UNPGEDRKQMWGQG-UHFFFAOYSA-N 0.000 description 3
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 3
- 208000030507 AIDS Diseases 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 229940126657 Compound 17 Drugs 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 description 3
- SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 241000223229 Trichophyton rubrum Species 0.000 description 3
- HUOFUOCSQCYFPW-UHFFFAOYSA-N [4-(trifluoromethoxy)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(OC(F)(F)F)C=C1 HUOFUOCSQCYFPW-UHFFFAOYSA-N 0.000 description 3
- BKFRPUDGODEFCO-UHFFFAOYSA-N [4-[4-(trifluoromethyl)phenyl]phenyl]methanamine;hydrochloride Chemical compound Cl.C1=CC(CN)=CC=C1C1=CC=C(C(F)(F)F)C=C1 BKFRPUDGODEFCO-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 230000001010 compromised effect Effects 0.000 description 3
- 238000012790 confirmation Methods 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- NFEZZTICAUWDHU-RDTXWAMCSA-N efinaconazole Chemical compound N1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)CCC(=C)CC1 NFEZZTICAUWDHU-RDTXWAMCSA-N 0.000 description 3
- 229960003937 efinaconazole Drugs 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 239000002158 endotoxin Substances 0.000 description 3
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 229920006008 lipopolysaccharide Polymers 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- MRQBIMZMDWOQLF-UHFFFAOYSA-N tert-butyl n-[2-(4-bromophenyl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCC1=CC=C(Br)C=C1 MRQBIMZMDWOQLF-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 2
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- PNFVIPIQXAIUAY-ZCFIWIBFSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC[C@H](C(O)=O)NC(=O)OC(C)(C)C PNFVIPIQXAIUAY-ZCFIWIBFSA-N 0.000 description 2
- ZIOCIQJXEKFHJO-MRVPVSSYSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoic acid Chemical compound CCCC[C@H](C(O)=O)NC(=O)OC(C)(C)C ZIOCIQJXEKFHJO-MRVPVSSYSA-N 0.000 description 2
- INWOAUUPYIXDHN-SSDOTTSWSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CCC[C@H](C(O)=O)NC(=O)OC(C)(C)C INWOAUUPYIXDHN-SSDOTTSWSA-N 0.000 description 2
- QIXDRLIEARGEQY-SSDOTTSWSA-N (2r)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoic acid Chemical compound CC[C@H](C(O)=O)N(C)C(=O)OC(C)(C)C QIXDRLIEARGEQY-SSDOTTSWSA-N 0.000 description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 2
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 2
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 2
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 2
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 2
- ZSZCXAOQVBEPME-UHFFFAOYSA-N 2-(4-bromophenyl)ethanamine Chemical compound NCCC1=CC=C(Br)C=C1 ZSZCXAOQVBEPME-UHFFFAOYSA-N 0.000 description 2
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 2
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 2
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 2
- LRQKBLKVPFOOQJ-UHFFFAOYSA-N 2-aminohexanoic acid Chemical compound CCCCC(N)C(O)=O LRQKBLKVPFOOQJ-UHFFFAOYSA-N 0.000 description 2
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 2
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 2
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 2
- 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 2
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- 108010020326 Caspofungin Proteins 0.000 description 2
- 229940127007 Compound 39 Drugs 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 108010049047 Echinocandins Proteins 0.000 description 2
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 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 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 241000286209 Phasianidae Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 206010041925 Staphylococcal infections Diseases 0.000 description 2
- 229920002472 Starch Polymers 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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 2
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 2
- 241000645784 [Candida] auris Species 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 2
- 150000003851 azoles Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 239000001273 butane Substances 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- JYIKNQVWKBUSNH-WVDDFWQHSA-N caspofungin Chemical compound C1([C@H](O)[C@@H](O)[C@H]2C(=O)N[C@H](C(=O)N3CC[C@H](O)[C@H]3C(=O)N[C@H](NCCN)[C@H](O)C[C@@H](C(N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N2)[C@@H](C)O)=O)NC(=O)CCCCCCCC[C@@H](C)C[C@@H](C)CC)[C@H](O)CCN)=CC=C(O)C=C1 JYIKNQVWKBUSNH-WVDDFWQHSA-N 0.000 description 2
- 229960003034 caspofungin Drugs 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- SCKYRAXSEDYPSA-UHFFFAOYSA-N ciclopirox Chemical compound ON1C(=O)C=C(C)C=C1C1CCCCC1 SCKYRAXSEDYPSA-UHFFFAOYSA-N 0.000 description 2
- 229960003749 ciclopirox Drugs 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125773 compound 10 Drugs 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940126086 compound 21 Drugs 0.000 description 2
- 229940126208 compound 22 Drugs 0.000 description 2
- 229940125833 compound 23 Drugs 0.000 description 2
- 229940125961 compound 24 Drugs 0.000 description 2
- 229940125846 compound 25 Drugs 0.000 description 2
- 229940125851 compound 27 Drugs 0.000 description 2
- 229940125807 compound 37 Drugs 0.000 description 2
- 229940127573 compound 38 Drugs 0.000 description 2
- 229940126540 compound 41 Drugs 0.000 description 2
- 229940125936 compound 42 Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 2
- 229940093471 ethyl oleate Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 2
- 229960004413 flucytosine Drugs 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000036737 immune function Effects 0.000 description 2
- 210000000987 immune system Anatomy 0.000 description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 2
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 150000004291 polyenes Chemical class 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012449 sabouraud dextrose agar Substances 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 2
- 229940031439 squalene Drugs 0.000 description 2
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- VLGPDTPSKUUHKR-UHFFFAOYSA-N tert-butyl n-(4-bromophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(Br)C=C1 VLGPDTPSKUUHKR-UHFFFAOYSA-N 0.000 description 2
- DJNCXSGGAMADNN-UHFFFAOYSA-N tert-butyl n-[(4-bromophenyl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1=CC=C(Br)C=C1 DJNCXSGGAMADNN-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- BQPPJGMMIYJVBR-UHFFFAOYSA-N (10S)-3c-Acetoxy-4.4.10r.13c.14t-pentamethyl-17c-((R)-1.5-dimethyl-hexen-(4)-yl)-(5tH)-Delta8-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products CC12CCC(OC(C)=O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C BQPPJGMMIYJVBR-UHFFFAOYSA-N 0.000 description 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
- MQHLMHIZUIDKOO-OKZBNKHCSA-N (2R,6S)-2,6-dimethyl-4-[(2S)-2-methyl-3-[4-(2-methylbutan-2-yl)phenyl]propyl]morpholine Chemical compound C1=CC(C(C)(C)CC)=CC=C1C[C@H](C)CN1C[C@@H](C)O[C@@H](C)C1 MQHLMHIZUIDKOO-OKZBNKHCSA-N 0.000 description 1
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- FNHHVPPSBFQMEL-KQHDFZBMSA-N (3S)-5-N-[(1S,5R)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide Chemical compound CNC(=O)c1cc(cc2c1OC[C@@]2(C)c1ccccc1)C(=O)NC1[C@H]2CC(O)C[C@@H]12 FNHHVPPSBFQMEL-KQHDFZBMSA-N 0.000 description 1
- CHGIKSSZNBCNDW-UHFFFAOYSA-N (3beta,5alpha)-4,4-Dimethylcholesta-8,24-dien-3-ol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21 CHGIKSSZNBCNDW-UHFFFAOYSA-N 0.000 description 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- QXOGPTXQGKQSJT-UHFFFAOYSA-N 1-amino-4-[4-(3,4-dimethylphenyl)sulfanylanilino]-9,10-dioxoanthracene-2-sulfonic acid Chemical compound Cc1ccc(Sc2ccc(Nc3cc(c(N)c4C(=O)c5ccccc5C(=O)c34)S(O)(=O)=O)cc2)cc1C QXOGPTXQGKQSJT-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- XYTLYKGXLMKYMV-UHFFFAOYSA-N 14alpha-methylzymosterol Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C XYTLYKGXLMKYMV-UHFFFAOYSA-N 0.000 description 1
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 description 1
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
- FPTJELQXIUUCEY-UHFFFAOYSA-N 3beta-Hydroxy-lanostan Natural products C1CC2C(C)(C)C(O)CCC2(C)C2C1C1(C)CCC(C(C)CCCC(C)C)C1(C)CC2 FPTJELQXIUUCEY-UHFFFAOYSA-N 0.000 description 1
- DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 1
- BNNMDMGPZUOOOE-UHFFFAOYSA-N 4-methylbenzenesulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1 BNNMDMGPZUOOOE-UHFFFAOYSA-N 0.000 description 1
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 description 1
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 241000193749 Bacillus coagulans Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- FPBWPNZFNGDSBB-UHFFFAOYSA-N CCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC(O)=O Chemical compound CCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC(O)=O FPBWPNZFNGDSBB-UHFFFAOYSA-N 0.000 description 1
- JMBVKGNIYHCDBR-UHFFFAOYSA-N CCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC(O)=O Chemical compound CCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC(O)=O JMBVKGNIYHCDBR-UHFFFAOYSA-N 0.000 description 1
- LEZLUORGHPPALL-UHFFFAOYSA-N CCCC(C(NCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC(O)=O Chemical compound CCCC(C(NCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC(O)=O LEZLUORGHPPALL-UHFFFAOYSA-N 0.000 description 1
- RLCDLDQQKHJXTQ-UHFFFAOYSA-N CCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC(O)=O Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC(O)=O RLCDLDQQKHJXTQ-UHFFFAOYSA-N 0.000 description 1
- RHBDTKLZQSAYBU-UHFFFAOYSA-N CCCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC(O)=O Chemical compound CCCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC(O)=O RHBDTKLZQSAYBU-UHFFFAOYSA-N 0.000 description 1
- ZMKULWALKRAABE-UHFFFAOYSA-N CCCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC(O)=O Chemical compound CCCCC(C(NCCC(C=C1)=CC=C1C(C=C1)=CC=C1OC(F)(F)F)=O)NC(O)=O ZMKULWALKRAABE-UHFFFAOYSA-N 0.000 description 1
- AEUGAIMNKTXNRI-UHFFFAOYSA-N CCCCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC(O)=O Chemical compound CCCCC(C(NCCC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1)=O)NC(O)=O AEUGAIMNKTXNRI-UHFFFAOYSA-N 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241001660259 Cereus <cactus> Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- 241000186427 Cutibacterium acnes Species 0.000 description 1
- 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 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 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 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108020004460 Fungal RNA Proteins 0.000 description 1
- 241000287828 Gallus gallus Species 0.000 description 1
- BKLIAINBCQPSOV-UHFFFAOYSA-N Gluanol Natural products CC(C)CC=CC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(O)C(C)(C)C4CC3 BKLIAINBCQPSOV-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- LOPKHWOTGJIQLC-UHFFFAOYSA-N Lanosterol Natural products CC(CCC=C(C)C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 LOPKHWOTGJIQLC-UHFFFAOYSA-N 0.000 description 1
- 241000186779 Listeria monocytogenes Species 0.000 description 1
- 206010024774 Localised infection Diseases 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 244000128833 Mimulus luteus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- LVDRREOUMKACNJ-BKMJKUGQSA-N N-[(2R,3S)-2-(4-chlorophenyl)-1-(1,4-dimethyl-2-oxoquinolin-7-yl)-6-oxopiperidin-3-yl]-2-methylpropane-1-sulfonamide Chemical compound CC(C)CS(=O)(=O)N[C@H]1CCC(=O)N([C@@H]1c1ccc(Cl)cc1)c1ccc2c(C)cc(=O)n(C)c2c1 LVDRREOUMKACNJ-BKMJKUGQSA-N 0.000 description 1
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 1
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
- CAHGCLMLTWQZNJ-UHFFFAOYSA-N Nerifoliol Natural products CC12CCC(O)C(C)(C)C1CCC1=C2CCC2(C)C(C(CCC=C(C)C)C)CCC21C CAHGCLMLTWQZNJ-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010029803 Nosocomial infection Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 241000235645 Pichia kudriavzevii Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000191963 Staphylococcus epidermidis Species 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 208000002474 Tinea Diseases 0.000 description 1
- 241000130764 Tinea Species 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 241000223238 Trichophyton Species 0.000 description 1
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 1
- WJEIYVAPNMUNIU-UHFFFAOYSA-N [Na].OC(O)=O Chemical compound [Na].OC(O)=O WJEIYVAPNMUNIU-UHFFFAOYSA-N 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 235000008206 alpha-amino acids Nutrition 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 229960003204 amorolfine Drugs 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003006 anti-agglomeration agent Substances 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 238000002827 antifungal susceptibility testing Methods 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940125844 compound 46 Drugs 0.000 description 1
- 229940127271 compound 49 Drugs 0.000 description 1
- 229940126545 compound 53 Drugs 0.000 description 1
- 229940127113 compound 57 Drugs 0.000 description 1
- 229940125900 compound 59 Drugs 0.000 description 1
- 229940126179 compound 72 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 229930003836 cresol Natural products 0.000 description 1
- 229940013361 cresol Drugs 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- QBSJHOGDIUQWTH-UHFFFAOYSA-N dihydrolanosterol Natural products CC(C)CCCC(C)C1CCC2(C)C3=C(CCC12C)C4(C)CCC(C)(O)C(C)(C)C4CC3 QBSJHOGDIUQWTH-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
- 230000008686 ergosterol biosynthesis Effects 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229960004884 fluconazole Drugs 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 244000000008 fungal human pathogen Species 0.000 description 1
- 244000053095 fungal pathogen Species 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000009422 growth inhibiting effect Effects 0.000 description 1
- 230000036541 health Effects 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
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229960004130 itraconazole Drugs 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940058690 lanosterol Drugs 0.000 description 1
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical compound C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 1
- VMPHSYLJUKZBJJ-UHFFFAOYSA-N lauric acid triglyceride Natural products CCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCC)COC(=O)CCCCCCCCCCC VMPHSYLJUKZBJJ-UHFFFAOYSA-N 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000001668 nucleic acid synthesis Methods 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000003090 pesticide formulation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LFQDNHWZDQTITF-UHFFFAOYSA-N tavaborole Chemical compound FC1=CC=C2B(O)OCC2=C1 LFQDNHWZDQTITF-UHFFFAOYSA-N 0.000 description 1
- 229960002636 tavaborole Drugs 0.000 description 1
- BWMISRWJRUSYEX-SZKNIZGXSA-N terbinafine hydrochloride Chemical compound Cl.C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 BWMISRWJRUSYEX-SZKNIZGXSA-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
- 201000004647 tinea pedis Diseases 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000000725 trifluoropropyl group Chemical group [H]C([H])(*)C([H])([H])C(F)(F)F 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
- 229960004740 voriconazole Drugs 0.000 description 1
- BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Classifications
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01L—SEMICONDUCTOR DEVICES NOT COVERED BY CLASS H10
- H01L29/00—Semiconductor devices specially adapted for rectifying, amplifying, oscillating or switching and having potential barriers; Capacitors or resistors having potential barriers, e.g. a PN-junction depletion layer or carrier concentration layer; Details of semiconductor bodies or of electrodes thereof ; Multistep manufacturing processes therefor
- H01L29/02—Semiconductor bodies ; Multistep manufacturing processes therefor
- H01L29/06—Semiconductor bodies ; Multistep manufacturing processes therefor characterised by their shape; characterised by the shapes, relative sizes, or dispositions of the semiconductor regions ; characterised by the concentration or distribution of impurities within semiconductor regions
- H01L29/08—Semiconductor bodies ; Multistep manufacturing processes therefor characterised by their shape; characterised by the shapes, relative sizes, or dispositions of the semiconductor regions ; characterised by the concentration or distribution of impurities within semiconductor regions with semiconductor regions connected to an electrode carrying current to be rectified, amplified or switched and such electrode being part of a semiconductor device which comprises three or more electrodes
- H01L29/0804—Emitter regions of bipolar transistors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/08—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
- C07C237/06—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Communicable Diseases (AREA)
- Engineering & Computer Science (AREA)
- Microelectronics & Electronic Packaging (AREA)
- Power Engineering (AREA)
- Epidemiology (AREA)
- Pest Control & Pesticides (AREA)
- General Physics & Mathematics (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Physics & Mathematics (AREA)
- Ceramic Engineering (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- Wood Science & Technology (AREA)
- Dentistry (AREA)
- Plant Pathology (AREA)
- Computer Hardware Design (AREA)
- Agronomy & Crop Science (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
また、本発明は、本発明のベンジルオキシベンジルアミニルアミノ酸誘導体を製造する方法を提供することを目的とする。
本発明において、前記ハロゲンは、フルオロ、クロロ、ブロモ、およびヨードの中から選択されてもよく、
本発明の化合物は、アミノアルカン酸をベースとし、それにビフェニル基を導入した誘導体化合物であってもよい。
具体的に、前記化合物は、
1)2-アミノ-N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)ブタンアミド;
2)2-アミノ-N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)ペンタンアミド;
3)2-アミノ-N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)ヘキサンアミド;
4)2-アミノ-N-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)ペンタンアミド;
5)N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)-2-(メチルアミノ)ブタンアミド;
6)N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)-2-(メチルアミノ)ペンタンアミド;
7)N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)-2-(メチルアミノ)ヘキサンアミド;
8)N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)-2-(ジメチルアミノ)ペンタンアミド;
9)2-アミノ-N-((3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メチル)ペンタンアミド;
10)2-アミノ-N-((3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メチル)ヘキサンアミド;
11)2-アミノ-N-((4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)メチル)ペンタンアミド;
12)2-アミノ-N-((4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)メチル)ヘキサンアミド;
13)2-アミノ-N-((4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)メチル)ペンタンアミド;
14)2-アミノ-N-((4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)メチル)ヘキサンアミド;
15)N-((3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メチル)-2-(メチルアミノ)ペンタンアミド;
16)2-(メチルアミノ)-N-((4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)メチル)ペンタンアミド;
17)N-((3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メチル)-2-(ジメチルアミノ)ペンタンアミド;
18)2-アミノ-N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
19)2-アミノ-N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
20)2-アミノ-N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;
21)2-アミノ-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
22)2-アミノ-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
23)2-アミノ-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;
24)2-アミノ-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
25)2-アミノ-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
26)2-アミノ-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;
27)2-アミノ-N-(2-(3’,4’-ジフルオロ-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
28)N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)-2-(メチルアミノ)ブタンアミド;
29)N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)-2-(メチルアミノ)ペンタンアミド;
30)N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)-2-(メチルアミノ)ヘキサンアミド;
31)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
32)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
33)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;
34)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
35)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
36)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;または
37)N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)-2-(ジメチルアミノ)ペンタンアミド;
であってもよく、これに制限されるものではない。
nは、0、1、2、3、4または5であり、
前記化学式中、
X’は、ハロゲンであり、
例えば、本発明の製造方法において、Boc保護基を除去するために行われる第2ステップは、塩酸と反応させて行ってもよいが、これに制限されない。
さらに、本発明は、前記薬学的組成物を、それを必要とする個体に投与するステップを含む、真菌感染疾患の治療方法を提供する。
先ず、本発明の化合物の合成に用いられた反応を一般化して下記のように整理した。
反応式a-ブトキシカルボニル保護基(Boc protecting group)の導入
反応式b-アミン基のメチル化
反応式C-1級アミン基上でBoc保護基の導入
反応式d-ビフェニルアミン塩酸塩誘導体の合成
反応式e-混合無水物結合(MAC)反応
反応式f-Boc保護基の除去
反応式g-アミン基のジメチル化
製造例
製造例1:(R)/(S)-2-((tert-ブトキシカルボニル)アミノ)ブタン酸(4)の製造
Rf=0.00(DCM 9.5:Methanol 0.5 and few drops of acetic acid);
製造例2:(R)/(S)-2-((tert-ブトキシカルボニル)アミノ)ペンタン酸(5)の製造
Rf=0.85(DCM 3:Methanol 17);
製造例3:(R)/(S)-2-((tert-ブトキシカルボニル)アミノ)ヘキサン酸(6)の製造
Rf=0.40(DCM 9:Methanol 1);
製造例4:(R)/(S)-2-((tert-ブトキシカルボニル)(メチル)アミノ)ブタン酸(7)の製造
Rf=0.45(DCM 9:Methanol 1 and few drops of acetic acid);
製造例5:(R)/(S)-2-((tert-ブトキシカルボニル)(メチル)アミノ)ペンタン酸(8)の製造
Rf=0.45(DCM 9:Methanol 1 and few drops of acetic acid);
製造例6:(R)/(S)-2-((tert-ブトキシカルボニル)(メチル)アミノ)ヘキサン酸(9)の製造
Rf=0.38(DCM 9:Methanol 1);
製造例7:tert-ブチル(4-ブロモフェネチル)カルバメート(12)の製造
Rf=0.36(EtOAc 1:n-hexane 5);
製造例8:3’,4’-ジクロロ-[1,1’-ビフェニル]-4-アミンヒドロクロリド(13)の製造
Rf=0.00(EtOAc 9:acetone 1);
製造例9:4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-アミンヒドロクロリド(14)の製造
Rf=0.00(EtOAc 9:acetone 1);
製造例10:2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メタン-1-アミンヒドロクロリド(15)の製造
Rf=0.00(EtOAc 9:acetone 1);
製造例11:(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)メタンアミンヒドロクロリド(16)の製造
Rf=0.00(EtOAc 9:acetone 1);
製造例12:(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)メタンアミンヒドロクロリド(17)の製造
Rf=0.00(EtOAc 9:acetone 1);
製造例13:2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エタン-1-アミンヒドロクロリド(18)の製造
Rf=0.00(EtOAc 9:acetone 1);
製造例14:2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エタン-1-アミンヒドロクロリド(19)の製造
Rf=0.00(EtOAc 9:acetone 1);
製造例15:2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エタン-1-アミンヒドロクロリド(20)の製造
Rf=0.00(EtOAc 9:acetone 1);
製造例16:2-(3’,4’-ジフルオロ-[1,1’-ビフェニル]-4-イル)エタン-1-アミンヒドロクロリド(21)の製造
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.33(EtOAc 1:n-hexane 3);
Rf=0.37(EtOAc 1:n-hexane 3);
Rf=0.50(EtOAc 1:n-hexane 3);
Rf=0.30(EtOAc 1:n-hexane 3);
Rf=0.50(EtOAc 1:n-hexane 3);
Rf=0.48(EtOAc 1:n-hexane 3);
Rf=0.55(EtOAc 1:n-hexane 3);
製造例24:(R)/(S)-2-アミノ-N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)ブタンアミドヒドロクロリド(29)の製造
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.04(EtOAc 1:n-hexane 3);
Rf=0.19(EtOAc 1:n-hexane 3);
Rf=0.17(EtOAc 1:n-hexane 3);
Rf=0.16(EtOAc 1:n-hexane 3);
Rf=0.09(EtOAc 1:n-hexane 3);
Rf=0.18(EtOAc 1:n-hexane 3);
Rf=0.18(EtOAc 1:n-hexane 3);
Rf=0.22(EtOAc 1:n-hexane 3);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.05(EtOAc 1:n-hexane 3);
Rf=0.26(EtOAc 1:n-hexane 3);
Rf=0.07(EtOAc 1:n-hexane 3);
Rf=0.16(EtOAc 1:n-hexane 3);
Rf=0.20(EtOAc 1:n-hexane 3);
Rf=0.13(EtOAc 1:n-hexane 3);
Rf=0.14(EtOAc 1:n-hexane 3);
Rf=0.12(EtOAc 1:n-hexane 3);
Rf=0.13(EtOAc 1:n-hexane 3);
Rf=0.10(EtOAc 1:n-hexane 3);
Rf=0.22(EtOAc 1:n-hexane 3);
Rf=0.33(EtOAc 1:n-hexane 3);
Rf=0.30(EtOAc 1:n-hexane 3);
Rf=0.15(EtOAc 1:n-hexane 3);
Rf=0.26(EtOAc 1:n-hexane 3);
Rf=0.32(EtOAc 1:n-hexane 3);
Rf=0.19(EtOAc 1:n-hexane 3);
Rf=0.18(EtOAc 1:n-hexane 3);
Rf=0.29(EtOAc 1:n-hexane 3);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:aetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
Rf=0.00(EtOAc 9:acetone 1);
実施例1:人体の病原性真菌類に対する抗真菌活性の分析
前記製造例で合成された化合物の日和見感染性真菌類に対する抗真菌活性の程度を測定するために、米国のCLSI(Clinical and Laboratory Standards Institute)ガイドラインに従い、インビトロ(in vitro)で抗真菌感受性検査を実施した。本実施例において、感染性真菌類であるクリプトコッカス・ネオフォルマンス(Cryptococcus neoformans)、カンジダ・アルビカンス(Candida albicans)、カンジダ・グラブラータ(Candida glabrata)、アスペルギルス・フミガーツス(Aspergillus fumigatus)を対象とし、化合物が真菌の発育を阻止可能な最小阻止濃度(MIC、Minimum Inhibitory Concentration)を測定し、表1に示した。MIC値(μg/ml)は、範囲値で記した。具体的に、カンジダ種(Candida species)およびクリプトコッカス・ネオフォルマンス(Cryptococcus neoformans)をSDA(Sabouraud dextrose agar)(Sigma-Aldrich)固体培地でそれぞれ24および48時間培養した。培養後、成長した単一コロニーを0.85%生理食塩水に懸濁し、懸濁液中の細胞濃度が1~5×106cells/mlになるようにした。前記細胞懸濁液をRPMI 1640液体培地(Sigma-Aldrich)に2000倍希釈し、最終濃度が5×102~2.5×103cells/mlの菌株懸濁液を準備した後、96-ウェルプレートに195μl/ウェルずつ分注した。その後、前記製造例により合成された化合物を2倍ずつ希釈し、最終濃度がそれぞれ128、64、32、16、8、4、2、1、0.5μg/mlになるように準備し、5μl/ウェルずつ処理して最終的に200μl/ウェルのテストセルを準備した。化合物を処理したカンジダ種(Candida species)は48時間、クリプトコッカス・ネオフォルマンス(C.neoformans)は35℃で72時間培養した後、96-ウェルプレートの底面を肉眼で観察して生育可否を確認し、MICを決めた。陽性対照群としては、人体に毒性は大きいが、代表的な抗真菌剤として知られたアムホテリシンB(Amphotericin B;AMB)を用いた。表1~表3にその結果を示した。
前記化合物74の抗真菌活性を確認するために、CLSI(Clinical and Laboratory Standards Institute)ガイドラインに従い、真菌の生長を阻害可能な最小濃度を確認するMIC(Minimum Inhibitory Concentration)を測定した。各真菌はYPD固体培地(Sigma-Aldrich)に塗抹し、トリコフィトン・ルブルム(T.rubrum)およびトリコフィトン・メンタグロフィテス(T.mentagrophytes)は最終濃度のmicroconidiaを2.5×103個、カンジダ・アルビカンス(Candida albicans)、カンジダ・グラブラータ(Candida glabrata)、およびクリプトコッカス・ネオフォルマンス(Cryptococcus neoformans)は最終濃度が2.5×103cfu/mlの濃度になるように菌株を準備した後、96-ウェルプレートに195μl/ウェルずつ分注した。化合物74を2倍ずつ希釈し、最終濃度がそれぞれ128、64、32、16、8、4、2、1、0.5μg/mlになるように準備し、5μl/ウェルずつ処理して最終的に200μl/ウェルになるようにする。化合物を処理したカンジダ種(Candida species)は48時間、クリプトコッカス・ネオフォルマンス(C.neoformans)およびトリコフィトン種(Trichophyton species)は35℃で72時間培養した後、96-ウェルプレートの底面を肉眼で観察して生長有無を確認し、MIC(μg/ml)を決めた。その結果を表4に示した。
化合物74の速効性効果を確認するために、カンジダ・アルビカンスに、化合物74、および市販中の薬物である、エフィナコナゾール(Efinaconazole)、タバボロール(Tavaborole)、テルビナフィン(Terbinafine)、またはシクロピロックス(Ciclopirox)を同じ濃度に同じ時間を処理し、カンジダ・アルビカンスの生長を確認した。カンジダ・アルビカンスを2.5×103cfu/mlの濃度で菌を準備し、96-ウェルプレートに195μl/ウェルずつ分注した。その後、化合物74および前記市販中の比較薬物を50μg/ml、100μg/mlでそれぞれ同様に30分間処理した後、YPD固体培地(Sigma-Aldrich)に塗抹し、成長する単一コロニーの数を確認した。その結果を図1に示した。これにより、化合物74が、市販中の競争薬物に比べ、速効性効果に優れることを確認することができた。
化合物74の殺真菌効果を確認するために、トリコフィトン・ルブルムに、化合物74、および市販中の薬物である、エフィナコナゾール(Efinaconazole)、アモロルフィン(Amorolfine)、テルビナフィン(Terbinafine)、シクロピロックス(Ciclopirox)、およびアムホテリシンB(Amphotericin B)を、MIC濃度の0.5、1、2、4、8、16倍数を定められた時間別に処理し、トリコフィトン・ルブルムの生長を確認してみた。トリコフィトン・ルブルムを6×103cfu/mlの濃度で菌を準備し、96-ウェルプレートに195μl/ウェルずつ分注した。その後、化合物74および競争薬物を各薬物のMIC濃度の0.5、1、2、4、8、16倍数で5μl処理して最終的に200μl/ウェルに合わせた後、それぞれ2、4、6、12、24、48、72、120時間処理し、各時間別にサンプルを取ってYPD固体培地に塗抹し、形成された単一コロニーの数を確認した。その結果を図2に示した。図2から確認されるように、化合物74は、市販中の薬物に比べ、MIC濃度が殺真菌濃度と同一であり、これは、他の薬物に比べ、低い濃度において殺真菌効果を有するということを示す。
化合物74の速効性効果を確認するために、カンジダ・アルビカンスが生物膜(biofilm)を形成するようにした後、化合物74、および市販中の薬物である、カスポファンギン(Caspofungin)、アムホテリシンB(Amphotericin B)、およびエフィナコナゾール(Efinaconazole)を4、8、16、32μg/mlの濃度で処理し、カンジダ・アルビカンスの生長を確認した。カンジダ・アルビカンスを2.5×103cfu/mlの濃度で準備し、96-ウェルプレートに90分間培養して生物膜を形成させた後、化合物74および前記比較薬物を処理し24時間後にカンジダ・アルビカンスの生長を確認した。その結果を図3に示した。図3から確認されるように、本発明の化合物74は、市販中の比較薬物に比べ、生物膜の破壊を通じたカンジダ・アルビカンスの生長抑制効果が顕著に優れるということを示す。
本発明で合成された化合物に対して、グラム陽性またはグラム陰性バクテリア、および多剤耐性バクテリアに対する抗菌活性を測定した。米国CLSI(Clinical and Laboratory Standards Institute)ガイドラインに従い、MICテストを行った。グラム陰性菌としてE.coli(-)、P.aeruginosa(-)、およびS.enterica(-)を用い、グラム陽性菌としてB.cereus(+)、B.subtilis(+)、B.coagulans(+)、L.monocytogenes(+)、M.luteus(+)、P.acnes(+)、S.epidermidis(+)、およびS.aureus(+)を用い、多剤耐性菌として黄色ブドウ球菌(lin-resistant Staphylococcus aureus、MRSA)を用いた。前記実験対象のバクテリアを培養した固体培地で形成された単一コロニーをOD600 0.1に合わせ、MHB液体培地(Sigma-Aldrich)に100倍で希釈して最終的にOD600 0.001になるようにし、96-ウェルプレートに100μl/ウェルずつ分注した。次に、本発明の化合物を2倍ずつ希釈し、最終濃度がそれぞれ64、32、16、8、4、2、1、0.5μg/mlになるように準備し、100μl/ウェルずつ処理して最終的に200μl/ウェルになるようにした。次いで、各バクテリア菌株を24時間37℃で培養した後、肉眼およびOD600を通じてMIC(μg/ml)を決めた。陽性対照群としては、NofloxacinおよびVancomycinを用いた。その結果を表5~表8に示した。
本発明で合成された化合物に対して、RAW264.7細胞においてインターロイキン6(IL-6)を誘導し、化合物の抗炎症効果を確認した。ラットのマクロファージであるRAW264.7細胞(韓国細胞株バンク)を12-ウェルプレートに初期に5×105細胞/ウェルで接種し、16~24時間37℃で培養した後、本発明で合成された化合物を、それぞれ最終濃度0または8μg/mlになるように、前記RAW264.7細胞を培養した培養液に処理し、37℃で1時間インキュベーションした。次に、リポ多糖(Lipopolysaccharide(LPS)、Sigma-aldrich、USA)を最終濃度1μg/mlになるように処理し、37℃で24時間培養してIL-6を誘導した。次に、Komabiotech社から入手したELISA kitを製造者の指示に従って用い、RAW264.7細胞で生成されたIL-6の量を確認した。その結果を表9に示した。表9において、IL-6の量は、LPSにより誘導された量および本発明の化合物の処理により減少した量の割合(%)で示した。
Claims (21)
- 前記R1およびR2は、それぞれ独立して、H、またはメチル、エチル、n-プロピル、イソプロピル、シクロプロピル、n-ブチル、イソブチル、シクロブチル、n-ペンチル、シクロペンチル、n-ヘキシル、またはシクロヘキシルであり、
前記R3は、メチル、エチル、n-プロピル、イソプロピル、シクロプロピル、n-ブチル、イソブチル、sec-ブチル、またはtert-ブチルである、請求項1に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩。 - 前記Xは、フルオロ、クロロ、トリフルオロメチル、およびトリフルオロメトキシからなる群から選択されるいずれか一つ、または互いに同一または異なる2個の置換基である、請求項1に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩。
- 前記Xは、p-フルオロ、m-フルオロ、p,m-ジフルオロ、p-クロロ、m-クロロ、p,m-ジクロロ、p-トリフルオロメチル、またはp-トリフルオロメトキシである、請求項3に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩。
- 前記化合物は、
1)2-アミノ-N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)ブタンアミド;
2)2-アミノ-N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)ペンタンアミド;
3)2-アミノ-N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)ヘキサンアミド;
4)2-アミノ-N-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)ペンタンアミド;
5)N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)-2-(メチルアミノ)ブタンアミド;
6)N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)-2-(メチルアミノ)ペンタンアミド;
7)N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)-2-(メチルアミノ)ヘキサンアミド;
8)N-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)-2-(ジメチルアミノ)ペンタンアミド;
9)2-アミノ-N-((3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メチル)ペンタンアミド;
10)2-アミノ-N-((3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メチル)ヘキサンアミド;
11)2-アミノ-N-((4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)メチル)ペンタンアミド;
12)2-アミノ-N-((4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)メチル)ヘキサンアミド;
13)2-アミノ-N-((4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)メチル)ペンタンアミド;
14)2-アミノ-N-((4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)メチル)ヘキサンアミド;
15)N-((3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メチル)-2-(メチルアミノ)ペンタンアミド;
16)2-(メチルアミノ)-N-((4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)メチル)ペンタンアミド;
17)N-((3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)メチル)-2-(ジメチルアミノ)ペンタンアミド;
18)2-アミノ-N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
19)2-アミノ-N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
20)2-アミノ-N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;
21)2-アミノ-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
22)2-アミノ-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
23)2-アミノ-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;
24)2-アミノ-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
25)2-アミノ-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
26)2-アミノ-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;
27)2-アミノ-N-(2-(3’,4’-ジフルオロ-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
28)N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)-2-(メチルアミノ)ブタンアミド;
29)N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)-2-(メチルアミノ)ペンタンアミド;
30)N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)-2-(メチルアミノ)ヘキサンアミド;
31)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
32)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
33)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメチル)-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;
34)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ブタンアミド;
35)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ペンタンアミド;
36)2-(メチルアミノ)-N-(2-(4’-(トリフルオロメトキシ)-[1,1’-ビフェニル]-4-イル)エチル)ヘキサンアミド;または
37)N-(2-(3’,4’-ジクロロ-[1,1’-ビフェニル]-4-イル)エチル)-2-(ジメチルアミノ)ペンタンアミド;である、請求項1に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩。 - 下記化学式2で表される、ブトキシカルボニル保護基(Boc protecting group)で保護された、アミノアルカン酸誘導体化合物を、下記化学式3で表される、1級アミン基を含むビフェニル誘導体化合物と反応させてペプチド結合を形成する第1ステップ;および
第1ステップで得られた化合物を酸と反応させてBoc保護基を除去する第2ステップ;を含む、
請求項1~5のいずれか1項に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩の製造方法:
前記化学式中、
nは、0、1、2、3、4または5であり、
R1、R2、およびR3は、それぞれ独立して、互いに同一または異なり、それぞれ独立して、水素、C1-7アルキル、ヒドロキシ、ハロゲン、ハロゲン化C1-7アルキル、C1-7アルキルオキシ、およびハロゲン化C1-7アルキルオキシの中から選択され、
Xは、ハロゲン基、ハロゲン化C1-7アルキル基、およびハロゲン化C1-7アルコキシ基からなる群から選択される、互いに同一または異なるm個(mは1~5の整数)の置換基である。 - 化学式2で表される、ブトキシカルボニル保護基(Boc protecting group)で保護された、アミノアルカン酸誘導体化合物は、下記化学式4で表されるアミノ酸誘導体をジ-tert-ブチルジカーボネート(di-tert-butyl dicarbonate、Boc anhydride)と反応させて準備したものである、請求項6に記載の製造方法:
R1’、R2、およびR3は、それぞれ独立して、互いに同一または異なり、それぞれ独立して、水素、C1-7アルキル、ヒドロキシ、ハロゲン、ハロゲン化C1-7アルキル、C1-7アルキルオキシ、およびハロゲン化C1-7アルキルオキシの中から選択される。 - 最終的に製造される化合物のR2がアルキルである場合、前記反応後、塩基の存在下で、ハロアルカンと反応させてアルキル化するステップをさらに行う、請求項7に記載の製造方法。
- 前記フェニルボロン酸誘導体との反応は、塩基の存在下で、金属触媒によるクロスカップリング反応により達成される、請求項9に記載の製造方法。
- 第1ステップは、N-メチルモルホリン(N-methylmorpholine;NMM)およびクロロギ酸イソブチル(isobutyl chloroformate;IBCF)の存在下で、有機溶媒において行われる無水結合反応により達成される、請求項6に記載の製造方法。
- 最終的に製造される化合物のR1およびR2が両方ともアルキルである場合、第2ステップの後、アミンをアルキル化して2級アミンを形成する第3ステップをさらに含む、請求項6に記載の製造方法。
- 請求項1~5のいずれか1項に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩を有効成分として含む抗真菌組成物。
- クリプトコッカス・ネオフォルマンス(Cryptococcus neoformans)、カンジダ・アルビカンス(Candida albicans)、カンジダ・グラブラータ(Candida glabrata)、またはアスペルギルス・フミガーツス(Aspergillus fumigatus)に対して抗真菌活性を示す、請求項13に記載の抗真菌組成物。
- 請求項1~5のいずれか1項に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩を有効成分として含む、真菌感染疾患の治療または予防用の薬学的組成物。
- 真菌感染疾患は、クリプトコッカス・ネオフォルマンス(Cryptococcus neoformans)、カンジダ・アルビカンス(Candida albicans)、カンジダ・グラブラータ(Candida glabrata)、またはアスペルギルス・フミガーツス(Aspergillus fumigatus)の感染により誘発される疾患である、請求項15に記載の薬学的組成物。
- 薬学的に許容可能な担体、希釈剤、または賦形剤をさらに含む、請求項15に記載の薬学的組成物。
- 請求項1~5のいずれか1項に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩を有効成分として含む抗菌組成物。
- グラム陰性細菌、グラム陽性細菌、または多剤耐性細菌に対して抗菌活性を示す、請求項18に記載の抗菌組成物。
- 請求項1~5のいずれか1項に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩を有効成分として含む、バクテリア感染疾患の治療または予防用の薬学的組成物。
- 請求項1~5のいずれか1項に記載の化合物、その立体異性体、またはその薬学的に許容可能な塩、および薬学的に許容可能な担体、希釈剤、または賦形剤を含む、抗炎症疾患の治療または予防用の薬学的組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2019-0075893 | 2019-06-25 | ||
KR20190075893 | 2019-06-25 | ||
PCT/KR2020/008306 WO2020262996A1 (ko) | 2019-06-25 | 2020-06-25 | 신규한 아미노알칸산에 바이페닐기를 도입한 유도체 화합물 및 이를 포함하는 항진균성 약학적 조성물 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022535613A true JP2022535613A (ja) | 2022-08-09 |
JP7290361B2 JP7290361B2 (ja) | 2023-06-13 |
Family
ID=74061024
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021577309A Active JP7290361B2 (ja) | 2019-06-25 | 2020-06-25 | 新規なアミノアルカン酸にビフェニル基を導入した誘導体化合物、およびこれを含む抗真菌薬学的組成物 |
Country Status (12)
Country | Link |
---|---|
US (4) | US11479526B2 (ja) |
EP (1) | EP3992177B1 (ja) |
JP (1) | JP7290361B2 (ja) |
KR (1) | KR102286897B1 (ja) |
CN (1) | CN114051496B (ja) |
AU (1) | AU2020303814B2 (ja) |
BR (1) | BR112021026076A2 (ja) |
CA (1) | CA3145394C (ja) |
CO (1) | CO2022000187A2 (ja) |
IL (1) | IL289445A (ja) |
MX (1) | MX2021015652A (ja) |
WO (1) | WO2020262996A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023128033A1 (ko) * | 2021-12-31 | 2023-07-06 | (주)앰틱스바이오 | 감염성 진균의 바이오필름 생성을 억제하는 신규한 항진균용 조성물 |
KR20230103336A (ko) | 2021-12-31 | 2023-07-07 | (주)앰틱스바이오 | 바이오필름 생성을 억제하는 신규한 항진균용 조성물 |
CN115784848B (zh) * | 2022-12-07 | 2024-04-30 | 成都理工大学 | 去甲欧花楸素衍生物及其制备方法和应用 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010108187A2 (en) * | 2009-03-20 | 2010-09-23 | Brandeis University | Compounds and methods for treating mammalian gastrointestinal microbial infections |
WO2012125832A2 (en) * | 2011-03-15 | 2012-09-20 | Rib-X Pharmaceuticals, Inc. | Antimicrobial agents |
WO2013131018A1 (en) * | 2012-03-02 | 2013-09-06 | Zalicus Pharmaceuticals Ltd. | Biaryl inhibitors of the sodium channel |
WO2018026811A2 (en) * | 2016-08-01 | 2018-02-08 | Ohio State Innovation Foundation | Antifungal agents |
WO2018026866A1 (en) * | 2016-08-03 | 2018-02-08 | Neuropore Therapies, Inc. | Lipid-substituted amino 1,2-and 1,3-diol compounds as modulators of tlr2 dimerization |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1283489B1 (it) * | 1996-07-23 | 1998-04-21 | Chiesi Farma Spa | Ammidi di alfa-amminoacidi,loro preparazione e loro impiego terapeutico |
US20070099958A1 (en) * | 2003-06-18 | 2007-05-03 | Prozymex A/S | Protease inhibitors |
US20060173023A1 (en) * | 2005-02-01 | 2006-08-03 | Wood Michael R | 2-(Bicyclo)alkylamino-derivatives as mediators of chronic pain and inflammation |
CA2639927A1 (en) * | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Substituted biaryl compounds for inflammation and immune-related uses |
CN102334033A (zh) | 2009-01-27 | 2012-01-25 | 霍洛吉克股份有限公司 | 生物学流体中供检测新生儿败血病用的生物标志 |
-
2020
- 2020-06-25 CN CN202080046307.9A patent/CN114051496B/zh active Active
- 2020-06-25 MX MX2021015652A patent/MX2021015652A/es unknown
- 2020-06-25 JP JP2021577309A patent/JP7290361B2/ja active Active
- 2020-06-25 CA CA3145394A patent/CA3145394C/en active Active
- 2020-06-25 BR BR112021026076A patent/BR112021026076A2/pt unknown
- 2020-06-25 EP EP20830693.6A patent/EP3992177B1/en active Active
- 2020-06-25 KR KR1020217000289A patent/KR102286897B1/ko active IP Right Grant
- 2020-06-25 WO PCT/KR2020/008306 patent/WO2020262996A1/ko unknown
- 2020-06-25 AU AU2020303814A patent/AU2020303814B2/en active Active
-
2021
- 2021-12-27 US US17/562,956 patent/US11479526B2/en active Active
- 2021-12-27 IL IL289445A patent/IL289445A/en unknown
-
2022
- 2022-01-13 CO CONC2022/0000187A patent/CO2022000187A2/es unknown
- 2022-09-19 US US17/948,165 patent/US20230056812A1/en active Pending
- 2022-09-19 US US17/948,157 patent/US20230053855A1/en active Pending
- 2022-09-19 US US17/948,162 patent/US20230067422A1/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010108187A2 (en) * | 2009-03-20 | 2010-09-23 | Brandeis University | Compounds and methods for treating mammalian gastrointestinal microbial infections |
WO2012125832A2 (en) * | 2011-03-15 | 2012-09-20 | Rib-X Pharmaceuticals, Inc. | Antimicrobial agents |
WO2013131018A1 (en) * | 2012-03-02 | 2013-09-06 | Zalicus Pharmaceuticals Ltd. | Biaryl inhibitors of the sodium channel |
WO2018026811A2 (en) * | 2016-08-01 | 2018-02-08 | Ohio State Innovation Foundation | Antifungal agents |
WO2018026866A1 (en) * | 2016-08-03 | 2018-02-08 | Neuropore Therapies, Inc. | Lipid-substituted amino 1,2-and 1,3-diol compounds as modulators of tlr2 dimerization |
Non-Patent Citations (2)
Title |
---|
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. Volume 27, Issue 19, JPN6022026912, 1 October 2017 (2017-10-01), pages 4571 - 4575, ISSN: 0004980813 * |
東北薬科大学紀要, vol. 4, JPN6022026914, 1957, pages 31 - 60, ISSN: 0004980812 * |
Also Published As
Publication number | Publication date |
---|---|
IL289445A (en) | 2022-02-01 |
WO2020262996A1 (ko) | 2020-12-30 |
US20230053855A1 (en) | 2023-02-23 |
US20220144755A1 (en) | 2022-05-12 |
BR112021026076A2 (pt) | 2022-03-29 |
CN114051496B (zh) | 2023-08-04 |
CN114051496A (zh) | 2022-02-15 |
EP3992177A4 (en) | 2023-08-16 |
CO2022000187A2 (es) | 2022-01-17 |
AU2020303814B2 (en) | 2023-02-23 |
US20230067422A1 (en) | 2023-03-02 |
CA3145394C (en) | 2024-01-09 |
US20230056812A1 (en) | 2023-02-23 |
US11479526B2 (en) | 2022-10-25 |
AU2020303814A1 (en) | 2022-02-03 |
EP3992177A1 (en) | 2022-05-04 |
MX2021015652A (es) | 2022-02-03 |
CA3145394A1 (en) | 2020-12-30 |
KR20210030343A (ko) | 2021-03-17 |
KR102286897B1 (ko) | 2021-08-09 |
JP7290361B2 (ja) | 2023-06-13 |
EP3992177B1 (en) | 2024-05-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7290361B2 (ja) | 新規なアミノアルカン酸にビフェニル基を導入した誘導体化合物、およびこれを含む抗真菌薬学的組成物 | |
US5674906A (en) | Stilbene compounds and pharmaceutical compositions containing them | |
JP5430559B2 (ja) | 新規ぺプチドデホルミラーゼ阻害化合物とその製造方法 | |
EA022336B1 (ru) | Производные фенилизоксазола и способ его получения | |
ES2203316B1 (es) | R-(-)-1-(2-(7-cloro-benzo(b)tiofen-3-il-metoxi)-2-(2,4-dicloro-fenil)-etil)1h-imidazol. | |
RU2690161C1 (ru) | 3,5-Замещенные производные тиазолидин-2,4-диона, обладающие противомикробной активностью | |
JP6516758B2 (ja) | 抗菌ペプチド模倣物 | |
JP3891503B2 (ja) | 製薬学的に活性なβ−アミノ酸類の許容性の改善 | |
KR102099980B1 (ko) | 알라닌 및 프롤린 아미노산의 기능적 유도체 화합물 및 이를 포함하는 약학적 조성물 | |
WO2023128033A1 (ko) | 감염성 진균의 바이오필름 생성을 억제하는 신규한 항진균용 조성물 | |
EP4268811A1 (en) | Novel derivative compound having biphenyl group introduced into amino-alkanoic acid and anti-inflammatory composition comprising same | |
US9255071B2 (en) | Compounds having antibacterial activity, process for their preparation and pharmaceutical compositions comprising them | |
KR20230103336A (ko) | 바이오필름 생성을 억제하는 신규한 항진균용 조성물 | |
SK311392A3 (en) | Use of substituted pyrolidines as medicines, effective matters and method of their preparation | |
EP0971916A1 (fr) | Derives de n-(arginyl)benzenesulfonamide et leur utilisation comme agents antithrombotiques |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211227 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20211227 |
|
A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20211227 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220629 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20220929 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20221125 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221228 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230203 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230502 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20230522 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230525 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7290361 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |