CN111848600B - 2,4,4-三取代二氢噁唑衍生物及其用途 - Google Patents
2,4,4-三取代二氢噁唑衍生物及其用途 Download PDFInfo
- Publication number
- CN111848600B CN111848600B CN202010749278.4A CN202010749278A CN111848600B CN 111848600 B CN111848600 B CN 111848600B CN 202010749278 A CN202010749278 A CN 202010749278A CN 111848600 B CN111848600 B CN 111848600B
- Authority
- CN
- China
- Prior art keywords
- methyl
- dihydrooxazole
- triazol
- phenyl
- biphenyl
- 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.)
- Active
Links
- -1 2,4, 4-trisubstituted dihydrooxazole Chemical class 0.000 title claims abstract description 27
- 239000003814 drug Substances 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- 206010017533 Fungal infection Diseases 0.000 claims abstract description 12
- 208000031888 Mycoses Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 61
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 241000222122 Candida albicans Species 0.000 claims description 12
- 238000006467 substitution reaction Methods 0.000 claims description 12
- 229940095731 candida albicans Drugs 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 241001225321 Aspergillus fumigatus Species 0.000 claims description 5
- 241000221204 Cryptococcus neoformans Species 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- FCMUIKBWXRDRMN-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-[4-(3-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC(=CC=C1)F)C1=C(C=C(C=C1)F)F FCMUIKBWXRDRMN-UHFFFAOYSA-N 0.000 claims description 4
- 241000223238 Trichophyton Species 0.000 claims description 4
- 229940091771 aspergillus fumigatus Drugs 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- GERWUIDIGDBAGO-UHFFFAOYSA-N 1-[4-[4-[4-phenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazol-2-yl]phenyl]piperazin-1-yl]ethanone Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)N1CCN(CC1)C(C)=O)C1=CC=CC=C1 GERWUIDIGDBAGO-UHFFFAOYSA-N 0.000 claims description 3
- CSAMVZSMGPDVPI-UHFFFAOYSA-N 2-(6-bromo-1-benzothiophen-2-yl)-4-(2,4-dichlorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Br)C2=C(C=C(C=C2)Cl)Cl CSAMVZSMGPDVPI-UHFFFAOYSA-N 0.000 claims description 3
- NSHUZONZAYANBP-UHFFFAOYSA-N 2-(6-bromo-1-benzothiophen-2-yl)-4-(2,4-difluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Br)C2=C(C=C(C=C2)F)F NSHUZONZAYANBP-UHFFFAOYSA-N 0.000 claims description 3
- OQJHOAOJXPNANZ-UHFFFAOYSA-N 2-(6-bromo-1-benzothiophen-2-yl)-4-(3,5-difluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Br)C2=CC(=CC(=C2)F)F OQJHOAOJXPNANZ-UHFFFAOYSA-N 0.000 claims description 3
- RDYVQGAFJVBGSH-UHFFFAOYSA-N 2-(6-bromo-1-benzothiophen-2-yl)-4-(4-chlorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Br)C2=CC=C(C=C2)Cl RDYVQGAFJVBGSH-UHFFFAOYSA-N 0.000 claims description 3
- XQGUANABEGFDSR-UHFFFAOYSA-N 2-(6-bromo-1-benzothiophen-2-yl)-4-(4-fluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Br)C2=CC=C(C=C2)F XQGUANABEGFDSR-UHFFFAOYSA-N 0.000 claims description 3
- KYZKMSXMEHOMGN-UHFFFAOYSA-N 2-(6-chloro-1-benzothiophen-2-yl)-4-(2,4-dichlorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Cl)C2=C(C=C(C=C2)Cl)Cl KYZKMSXMEHOMGN-UHFFFAOYSA-N 0.000 claims description 3
- DYKQCQVMNLYFGC-UHFFFAOYSA-N 2-(6-chloro-1-benzothiophen-2-yl)-4-(2,4-difluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Cl)C2=C(C=C(C=C2)F)F DYKQCQVMNLYFGC-UHFFFAOYSA-N 0.000 claims description 3
- KQFPZMUJFKULRN-UHFFFAOYSA-N 2-(6-chloro-1-benzothiophen-2-yl)-4-(3,5-difluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Cl)C2=CC(=CC(=C2)F)F KQFPZMUJFKULRN-UHFFFAOYSA-N 0.000 claims description 3
- HDRXGGWSEWGELG-UHFFFAOYSA-N 2-(6-chloro-1-benzothiophen-2-yl)-4-(4-chlorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Cl)C2=CC=C(C=C2)Cl HDRXGGWSEWGELG-UHFFFAOYSA-N 0.000 claims description 3
- KTOAMCQQWXLGKV-UHFFFAOYSA-N 2-(6-chloro-1-benzothiophen-2-yl)-4-(4-fluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Cl)C2=CC=C(C=C2)F KTOAMCQQWXLGKV-UHFFFAOYSA-N 0.000 claims description 3
- SRKWWDJZMJKUBV-UHFFFAOYSA-N 2-(6-chloro-1-benzothiophen-2-yl)-4-(4-fluorophenyl)-4-(tetrazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=NN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)Cl)C2=CC=C(C=C2)F SRKWWDJZMJKUBV-UHFFFAOYSA-N 0.000 claims description 3
- JIBRROSJWTWYEC-UHFFFAOYSA-N 2-(6-fluoro-1-benzothiophen-2-yl)-4-(4-fluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)F)C2=CC=C(C=C2)F JIBRROSJWTWYEC-UHFFFAOYSA-N 0.000 claims description 3
- KDGLBQTTXTVHQZ-UHFFFAOYSA-N 2-phenyl-5-[4-[4-phenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazol-2-yl]phenyl]-1,3,4-oxadiazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C=1OC(=NN1)C1=CC=CC=C1)C1=CC=CC=C1 KDGLBQTTXTVHQZ-UHFFFAOYSA-N 0.000 claims description 3
- LUMBSCWASVCSFB-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-(4-thiophen-3-ylphenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CSC=C1)C1=C(C=C(C=C1)Cl)Cl LUMBSCWASVCSFB-UHFFFAOYSA-N 0.000 claims description 3
- NMGKXVFWEOQFJT-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-(6-fluoro-1-benzothiophen-2-yl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)F)C2=C(C=C(C=C2)Cl)Cl NMGKXVFWEOQFJT-UHFFFAOYSA-N 0.000 claims description 3
- PXGSQTSUZKLFDR-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-[4-(2-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=C(C=CC=C1)F)C1=C(C=C(C=C1)Cl)Cl PXGSQTSUZKLFDR-UHFFFAOYSA-N 0.000 claims description 3
- CGTVOUSDNWQTPD-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-[4-(furan-3-yl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=COC=C1)C1=C(C=C(C=C1)Cl)Cl CGTVOUSDNWQTPD-UHFFFAOYSA-N 0.000 claims description 3
- CJXRFXYYMYXHLL-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-(4-thiophen-3-ylphenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CSC=C1)C1=C(C=C(C=C1)F)F CJXRFXYYMYXHLL-UHFFFAOYSA-N 0.000 claims description 3
- GCYKPNFVRKLBMD-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-[4-(2-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=C(C=CC=C1)F)C1=C(C=C(C=C1)F)F GCYKPNFVRKLBMD-UHFFFAOYSA-N 0.000 claims description 3
- IMXXINRINZRAFV-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-[4-(furan-3-yl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=COC=C1)C1=C(C=C(C=C1)F)F IMXXINRINZRAFV-UHFFFAOYSA-N 0.000 claims description 3
- DYJCMBOEWYSYCV-UHFFFAOYSA-N 4-(3,5-difluorophenyl)-2-(6-fluoro-1-benzothiophen-2-yl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)F)C2=CC(=CC(=C2)F)F DYJCMBOEWYSYCV-UHFFFAOYSA-N 0.000 claims description 3
- RFBQORKKYIOIDP-UHFFFAOYSA-N 4-(3,5-difluorophenyl)-2-[4-(2-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=C(C=CC=C1)F)C1=CC(=CC(=C1)F)F RFBQORKKYIOIDP-UHFFFAOYSA-N 0.000 claims description 3
- JREZIFIQNLDOJK-UHFFFAOYSA-N 4-(3,5-difluorophenyl)-2-[4-(3-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC(=CC=C1)F)C1=CC(=CC(=C1)F)F JREZIFIQNLDOJK-UHFFFAOYSA-N 0.000 claims description 3
- LFLUGLJGCZWYDE-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(4-thiophen-3-ylphenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CSC=C1)C1=CC=C(C=C1)Cl LFLUGLJGCZWYDE-UHFFFAOYSA-N 0.000 claims description 3
- HMNORGYSISZKOU-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[4-(2-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=C(C=CC=C1)F)C1=CC=C(C=C1)Cl HMNORGYSISZKOU-UHFFFAOYSA-N 0.000 claims description 3
- NQTIQHNZMXZUFX-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[4-(3-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC(=CC=C1)F)C1=CC=C(C=C1)Cl NQTIQHNZMXZUFX-UHFFFAOYSA-N 0.000 claims description 3
- LIVLINYHTKMLRN-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-[4-(furan-3-yl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=COC=C1)C1=CC=C(C=C1)Cl LIVLINYHTKMLRN-UHFFFAOYSA-N 0.000 claims description 3
- VLNHLPDQPVIMBC-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-(4-thiophen-3-ylphenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CSC=C1)C1=CC=C(C=C1)F VLNHLPDQPVIMBC-UHFFFAOYSA-N 0.000 claims description 3
- WTXFRMCKLJLVDP-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-[4-(2-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=C(C=CC=C1)F)C1=CC=C(C=C1)F WTXFRMCKLJLVDP-UHFFFAOYSA-N 0.000 claims description 3
- GRRCEUHIAGYRDK-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-[4-(3-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC(=CC=C1)F)C1=CC=C(C=C1)F GRRCEUHIAGYRDK-UHFFFAOYSA-N 0.000 claims description 3
- MXLNMGLQUWCDGY-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-[4-(furan-3-yl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=COC=C1)C1=CC=C(C=C1)F MXLNMGLQUWCDGY-UHFFFAOYSA-N 0.000 claims description 3
- 241000223229 Trichophyton rubrum Species 0.000 claims description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- PCGOFYSHHFSECI-UHFFFAOYSA-N 4-(2,4-dichlorophenyl)-2-[4-(3-fluorophenyl)phenyl]-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC(=CC=C1)F)C1=C(C=C(C=C1)Cl)Cl PCGOFYSHHFSECI-UHFFFAOYSA-N 0.000 claims description 2
- YZECXNPQWNHMHU-UHFFFAOYSA-N N-[4-[4-phenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazol-2-yl]phenyl]benzamide Chemical compound C(C1=CC=CC=C1)(=O)NC1=CC=C(C=C1)C=1OCC(N1)(C1=CC=CC=C1)CN1N=CN=C1 YZECXNPQWNHMHU-UHFFFAOYSA-N 0.000 claims description 2
- 241000893976 Nannizzia gypsea Species 0.000 claims description 2
- 241000893966 Trichophyton verrucosum Species 0.000 claims description 2
- 241000222126 [Candida] glabrata Species 0.000 claims description 2
- 208000032343 candida glabrata infection Diseases 0.000 claims description 2
- 241001480037 Microsporum Species 0.000 claims 17
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 9
- 241000186063 Arthrobacter Species 0.000 claims 5
- 241000223230 Trichosporon Species 0.000 claims 5
- 241000893451 Arthroderma Species 0.000 claims 4
- 241000219071 Malvaceae Species 0.000 claims 4
- 241001045770 Trichophyton mentagrophytes Species 0.000 claims 3
- 241000235389 Absidia Species 0.000 claims 2
- 241000228197 Aspergillus flavus Species 0.000 claims 2
- 241000228245 Aspergillus niger Species 0.000 claims 2
- 241000079253 Byssochlamys spectabilis Species 0.000 claims 2
- 241000222120 Candida <Saccharomycetales> Species 0.000 claims 2
- 241001480036 Epidermophyton floccosum Species 0.000 claims 2
- 241000248325 Exophiala dermatitidis Species 0.000 claims 2
- 241000427940 Fusarium solani Species 0.000 claims 2
- 244000168141 Geotrichum candidum Species 0.000 claims 2
- 235000017388 Geotrichum candidum Nutrition 0.000 claims 2
- 244000286779 Hansenula anomala Species 0.000 claims 2
- 235000014683 Hansenula anomala Nutrition 0.000 claims 2
- 241000228404 Histoplasma capsulatum Species 0.000 claims 2
- 241001057811 Paracoccus <mealybug> Species 0.000 claims 2
- 241000235648 Pichia Species 0.000 claims 2
- 241000233872 Pneumocystis carinii Species 0.000 claims 2
- 240000005384 Rhizopus oryzae Species 0.000 claims 2
- 235000013752 Rhizopus oryzae Nutrition 0.000 claims 2
- 241000223254 Rhodotorula mucilaginosa Species 0.000 claims 2
- 241000222481 Schizophyllum commune Species 0.000 claims 2
- 241001523006 Talaromyces marneffei Species 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 1
- 241000228405 Blastomyces dermatitidis Species 0.000 claims 1
- 241000282465 Canis Species 0.000 claims 1
- 241000223233 Cutaneotrichosporon cutaneum Species 0.000 claims 1
- 241001634927 Cutaneotrichosporon mucoides Species 0.000 claims 1
- 241000199026 Gyptis <bristle worm> Species 0.000 claims 1
- 241001444195 Madurella Species 0.000 claims 1
- 241000555688 Malassezia furfur Species 0.000 claims 1
- 241000779599 Malpighia Species 0.000 claims 1
- 241000031003 Monascus ruber Species 0.000 claims 1
- 241000306281 Mucor ambiguus Species 0.000 claims 1
- 241000186359 Mycobacterium Species 0.000 claims 1
- 241000893974 Nannizzia fulva Species 0.000 claims 1
- 241001226034 Nectria <echinoderm> Species 0.000 claims 1
- 241000222640 Polyporus Species 0.000 claims 1
- 241000589516 Pseudomonas Species 0.000 claims 1
- 241000094595 Sarcoporia Species 0.000 claims 1
- 241000132889 Scedosporium Species 0.000 claims 1
- 241001533598 Septoria Species 0.000 claims 1
- 241001149963 Sporothrix schenckii Species 0.000 claims 1
- 241001480050 Trichophyton violaceum Species 0.000 claims 1
- 241001634961 Trichosporon asahii Species 0.000 claims 1
- 241000601794 Trichothecium Species 0.000 claims 1
- 241001530097 Verbascum Species 0.000 claims 1
- 241000700605 Viruses Species 0.000 claims 1
- 241000235013 Yarrowia Species 0.000 claims 1
- 241000645784 [Candida] auris Species 0.000 claims 1
- 125000005257 alkyl acyl group Chemical group 0.000 claims 1
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 1
- 238000010276 construction Methods 0.000 claims 1
- 244000053095 fungal pathogen Species 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 229940055035 trichophyton verrucosum Drugs 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 29
- 238000002360 preparation method Methods 0.000 abstract description 14
- 239000000651 prodrug Substances 0.000 abstract description 14
- 229940002612 prodrug Drugs 0.000 abstract description 14
- 239000012453 solvate Substances 0.000 abstract description 11
- 150000004677 hydrates Chemical class 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 74
- 239000000543 intermediate Substances 0.000 description 48
- 238000005160 1H NMR spectroscopy Methods 0.000 description 38
- 239000011734 sodium Substances 0.000 description 31
- 238000006243 chemical reaction Methods 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 17
- 230000000843 anti-fungal effect Effects 0.000 description 16
- 238000000034 method Methods 0.000 description 15
- 238000001914 filtration Methods 0.000 description 14
- 238000005406 washing Methods 0.000 description 13
- 125000000217 alkyl group Chemical group 0.000 description 11
- 229940121375 antifungal agent Drugs 0.000 description 11
- 239000002274 desiccant Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000007832 Na2SO4 Substances 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000001704 evaporation Methods 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 239000012980 RPMI-1640 medium Substances 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 241000233866 Fungi Species 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 229910006124 SOCl2 Inorganic materials 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 238000000227 grinding Methods 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000000829 suppository Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- ZABMHLDQFJHDSC-UHFFFAOYSA-N 2,3-dihydro-1,3-oxazole Chemical class C1NC=CO1 ZABMHLDQFJHDSC-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 201000007336 Cryptococcosis Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 229960004884 fluconazole Drugs 0.000 description 3
- 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 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000865 liniment Substances 0.000 description 3
- 231100000053 low toxicity Toxicity 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 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 3
- 229960004740 voriconazole Drugs 0.000 description 3
- 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 2
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 2
- NVHGSCJXDRTMBB-UHFFFAOYSA-N 2,4-diphenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=CC=C1)C1=CC=CC=C1 NVHGSCJXDRTMBB-UHFFFAOYSA-N 0.000 description 2
- ZYHTUICRXAAALG-UHFFFAOYSA-N 2-(1-benzofuran-2-yl)-4-phenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C=1OC2=C(C1)C=CC=C2)C2=CC=CC=C2 ZYHTUICRXAAALG-UHFFFAOYSA-N 0.000 description 2
- 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 2
- VRYCTTIYXYKRDN-UHFFFAOYSA-N 2-[4-(furan-3-yl)phenyl]-4-phenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=COC=C1)C1=CC=CC=C1 VRYCTTIYXYKRDN-UHFFFAOYSA-N 0.000 description 2
- REBNFRJQCRUNEI-UHFFFAOYSA-N 2-naphthalen-2-yl-4-phenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=CC=CC=C2C=C1)C1=CC=CC=C1 REBNFRJQCRUNEI-UHFFFAOYSA-N 0.000 description 2
- OGLAHQNDFOEYAO-UHFFFAOYSA-N 4-(1,3-dihydrotetrazol-2-ylmethyl)-4-phenyl-2-(4-phenylphenyl)-5H-1,3-oxazole Chemical compound N1N(NN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC=CC=C1)C1=CC=CC=C1 OGLAHQNDFOEYAO-UHFFFAOYSA-N 0.000 description 2
- NHZPQWCZMBAERW-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-2-(6-fluoro-1-benzothiophen-2-yl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)F)C2=C(C=C(C=C2)F)F NHZPQWCZMBAERW-UHFFFAOYSA-N 0.000 description 2
- MXPWRXHSQFYHCI-UHFFFAOYSA-N 4-(2,4-difluorophenyl)-4-(1,2,4-triazol-1-ylmethyl)-2-[5-(trifluoromethoxy)-1-benzothiophen-2-yl]-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=CC(=C2)OC(F)(F)F)C2=C(C=C(C=C2)F)F MXPWRXHSQFYHCI-UHFFFAOYSA-N 0.000 description 2
- OFOYOKWGTOFDDC-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-(6-fluoro-1-benzothiophen-2-yl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=C(C=C2)F)C2=CC=C(C=C2)Cl OFOYOKWGTOFDDC-UHFFFAOYSA-N 0.000 description 2
- NLAFMOSZPPMYAX-UHFFFAOYSA-N 4-(imidazol-1-ylmethyl)-2-(4-phenylphenyl)-4-propan-2-yl-5H-1,3-oxazole Chemical compound N1(C=NC=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC=CC=C1)C(C)C NLAFMOSZPPMYAX-UHFFFAOYSA-N 0.000 description 2
- WDFZKTFMOYOIIP-UHFFFAOYSA-N 4-(imidazol-1-ylmethyl)-4-methyl-2-(4-phenylphenyl)-5H-1,3-oxazole Chemical compound N1(C=NC=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC=CC=C1)C WDFZKTFMOYOIIP-UHFFFAOYSA-N 0.000 description 2
- ZOJXXUDGNJOVGD-UHFFFAOYSA-N 4-(imidazol-1-ylmethyl)-4-phenyl-2-(4-phenylphenyl)-5H-1,3-oxazole Chemical compound N1(C=NC=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC=CC=C1)C1=CC=CC=C1 ZOJXXUDGNJOVGD-UHFFFAOYSA-N 0.000 description 2
- HLYXCEXHCJAMMQ-UHFFFAOYSA-N 4-benzyl-4-(imidazol-1-ylmethyl)-2-(4-phenylphenyl)-5H-1,3-oxazole Chemical compound N1(C=NC=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC=CC=C1)CC1=CC=CC=C1 HLYXCEXHCJAMMQ-UHFFFAOYSA-N 0.000 description 2
- UXJXWSMWDWIZMU-UHFFFAOYSA-N 4-cyclopropyl-4-(imidazol-1-ylmethyl)-2-(4-phenylphenyl)-5H-1,3-oxazole Chemical compound N1(C=NC=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC=CC=C1)C1CC1 UXJXWSMWDWIZMU-UHFFFAOYSA-N 0.000 description 2
- GUAPGTXZVNZXMT-UHFFFAOYSA-N 4-phenyl-2-(4-phenylmethoxyphenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)OCC1=CC=CC=C1)C1=CC=CC=C1 GUAPGTXZVNZXMT-UHFFFAOYSA-N 0.000 description 2
- XDNJVFGQQWLJJB-UHFFFAOYSA-N 4-phenyl-2-(4-phenylphenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CC=CC=C1)C1=CC=CC=C1 XDNJVFGQQWLJJB-UHFFFAOYSA-N 0.000 description 2
- ONTQBMCDBMDQSM-UHFFFAOYSA-N 4-phenyl-2-(4-thiophen-3-ylphenyl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC=C(C=C1)C1=CSC=C1)C1=CC=CC=C1 ONTQBMCDBMDQSM-UHFFFAOYSA-N 0.000 description 2
- DKQNGFWHSZZAPT-UHFFFAOYSA-N 4-phenyl-2-(5-phenylthiophen-2-yl)-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C=1SC(=CC1)C1=CC=CC=C1)C1=CC=CC=C1 DKQNGFWHSZZAPT-UHFFFAOYSA-N 0.000 description 2
- SLWIFZYRJHUDME-UHFFFAOYSA-N 5-[difluoro(phenyl)methyl]-4-(imidazol-1-ylmethyl)-2-(4-phenylphenyl)-4,5-dihydro-1,3-oxazole Chemical compound N1(C=NC=C1)CC1N=C(OC1C(C1=CC=CC=C1)(F)F)C1=CC=C(C=C1)C1=CC=CC=C1 SLWIFZYRJHUDME-UHFFFAOYSA-N 0.000 description 2
- NRZSZHADDLIIQD-UHFFFAOYSA-N 5-[fluoro(phenyl)methyl]-4-(imidazol-1-ylmethyl)-2-(4-phenylphenyl)-4,5-dihydro-1,3-oxazole Chemical compound N1(C=NC=C1)CC1N=C(OC1C(C1=CC=CC=C1)F)C1=CC=C(C=C1)C1=CC=CC=C1 NRZSZHADDLIIQD-UHFFFAOYSA-N 0.000 description 2
- TWLMPPSSAQUMSE-UHFFFAOYSA-N 5-phenyl-3-[4-phenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazol-2-yl]-1,2-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=NOC(=C1)C1=CC=CC=C1)C1=CC=CC=C1 TWLMPPSSAQUMSE-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 2
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 2
- 241000222178 Candida tropicalis Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-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
- 108010010803 Gelatin Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 102100021695 Lanosterol 14-alpha demethylase Human genes 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-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
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 150000001408 amides 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
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960004022 clotrimazole Drugs 0.000 description 2
- VNFPBHJOKIVQEB-UHFFFAOYSA-N clotrimazole Chemical compound ClC1=CC=CC=C1C(N1C=NC=C1)(C=1C=CC=CC=1)C1=CC=CC=C1 VNFPBHJOKIVQEB-UHFFFAOYSA-N 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- GWZCCUDJHOGOSO-UHFFFAOYSA-N diphenic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=CC=C1C(O)=O GWZCCUDJHOGOSO-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000008686 ergosterol biosynthesis Effects 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 229960004130 itraconazole Drugs 0.000 description 2
- 229960004125 ketoconazole Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229940040145 liniment Drugs 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229960002509 miconazole Drugs 0.000 description 2
- 239000012982 microporous membrane Substances 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000000962 organic group Chemical group 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229960001589 posaconazole Drugs 0.000 description 2
- RAGOYPUPXAKGKH-XAKZXMRKSA-N posaconazole Chemical compound O=C1N([C@H]([C@H](C)O)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3C[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 RAGOYPUPXAKGKH-XAKZXMRKSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 238000010998 test method Methods 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
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- ZAIIGYZYRVYMNK-UHFFFAOYSA-N 2-(1-benzothiophen-2-yl)-4-phenyl-4-(1,2,4-triazol-1-ylmethyl)-5H-1,3-oxazole Chemical compound N1(N=CN=C1)CC1(N=C(OC1)C1=CC2=C(S1)C=CC=C2)C2=CC=CC=C2 ZAIIGYZYRVYMNK-UHFFFAOYSA-N 0.000 description 1
- KHZOJCQBHJUJFY-UHFFFAOYSA-N 2-[4-(2-methylpyridin-4-yl)phenyl]-n-(4-pyridin-3-ylphenyl)acetamide Chemical compound C1=NC(C)=CC(C=2C=CC(CC(=O)NC=3C=CC(=CC=3)C=3C=NC=CC=3)=CC=2)=C1 KHZOJCQBHJUJFY-UHFFFAOYSA-N 0.000 description 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- HIVLTBKWCUBEQJ-UHFFFAOYSA-N 3-amino-6-pyridin-4-yl-n-[4-(trifluoromethyl)phenyl]thieno[2,3-b]pyridine-2-carboxamide Chemical compound C=1C=C2C(N)=C(C(=O)NC=3C=CC(=CC=3)C(F)(F)F)SC2=NC=1C1=CC=NC=C1 HIVLTBKWCUBEQJ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
- JMIFGARJSWXZSH-UHFFFAOYSA-N DMH1 Chemical compound C1=CC(OC(C)C)=CC=C1C1=CN2N=CC(C=3C4=CC=CC=C4N=CC=3)=C2N=C1 JMIFGARJSWXZSH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 108010049047 Echinocandins Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 101710146773 Lanosterol 14-alpha demethylase Proteins 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 108010013803 Sterol 14-Demethylase Proteins 0.000 description 1
- 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 1
- 208000002474 Tinea Diseases 0.000 description 1
- 241000121220 Tricholoma matsutake Species 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229940057995 liquid paraffin Drugs 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
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- NDBQJIBNNUJNHA-AENDTGMFSA-N methyl (2r)-2-amino-3-hydroxypropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](N)CO NDBQJIBNNUJNHA-AENDTGMFSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000746 purification Methods 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
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000004304 subcutaneous tissue Anatomy 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010749278.4A CN111848600B (zh) | 2020-07-30 | 2020-07-30 | 2,4,4-三取代二氢噁唑衍生物及其用途 |
| PCT/CN2021/109144 WO2022022616A1 (fr) | 2020-07-30 | 2021-07-29 | Dérivés de dihydrooxazole 2,4,4-trisubstitués, leurs procédés de préparation et leur utilisation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010749278.4A CN111848600B (zh) | 2020-07-30 | 2020-07-30 | 2,4,4-三取代二氢噁唑衍生物及其用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111848600A CN111848600A (zh) | 2020-10-30 |
| CN111848600B true CN111848600B (zh) | 2021-12-07 |
Family
ID=72946418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010749278.4A Active CN111848600B (zh) | 2020-07-30 | 2020-07-30 | 2,4,4-三取代二氢噁唑衍生物及其用途 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN111848600B (fr) |
| WO (1) | WO2022022616A1 (fr) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111848600B (zh) * | 2020-07-30 | 2021-12-07 | 沈阳药科大学 | 2,4,4-三取代二氢噁唑衍生物及其用途 |
| CN114605282A (zh) * | 2022-03-22 | 2022-06-10 | 宿迁盛基医药科技有限公司 | 一种孟鲁司特钠侧链中间体的制备方法 |
| CN114605283A (zh) * | 2022-03-22 | 2022-06-10 | 宿迁盛基医药科技有限公司 | 一种高效制备孟鲁司特钠侧链中间体的方法 |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4338327A (en) * | 1978-10-06 | 1982-07-06 | Janssen Pharmaceutica, N.V. | Substituted 1-(2-aryl-1,3-dioxolan-2-ylmethyl)-1H-1,2,4-triazoles |
| US4384879A (en) * | 1980-07-15 | 1983-05-24 | Ciba-Geigy Corporation | 4-(1H-Azolylmethyl)-1,3-dioxolan-5-one derivatives, production thereof and use thereof as growth regulators and/or microbicides |
| GB2095236B (en) * | 1981-03-18 | 1985-03-27 | Ici Plc | Heterocyclylmethyl-substituted dioxolanes and their use as fungicides |
| JPS58128383A (ja) * | 1982-01-26 | 1983-07-30 | Sumitomo Chem Co Ltd | トリアゾ−ル系化合物、その製造法およびこれを有効成分として含有する農園芸用殺菌剤、植物生長調節剤または除草剤 |
| EP0094167A3 (fr) * | 1982-05-12 | 1984-07-04 | Fbc Limited | Azolyl fongicides et régulateurs de croissance des plantes et compositions les contenant |
| US4785117A (en) * | 1987-10-02 | 1988-11-15 | Pennwalt Corporation | 5,5-disubstituted-3-phenyl-3-phenyl-3-[(1H-imidazol-1-ylmethyl) or (1H-1,2,4-triazol-1-ylmethyl)]-2-methylisoxazolidine derivatives (IR 3012) |
| US4835283A (en) * | 1988-03-07 | 1989-05-30 | Pennwalt Corporation | 3,5-diphenyl-3-[(1H-imidazol-1-ylmethyl) or (1H-1,2,4-triazol-1-ylmethyl)]-2 |
| DE4013723A1 (de) * | 1990-04-28 | 1991-10-31 | Basf Ag | 5-(1,2,4-triazol-1-ylmethyl)-isoxazoline |
| ES2038906B1 (es) * | 1991-09-04 | 1994-02-16 | Uriach & Cia Sa J | Procedimiento para la obtencion de nuevas oxazoilidinas. |
| JPH06263757A (ja) * | 1993-03-10 | 1994-09-20 | Kaken Pharmaceut Co Ltd | アゾール系化合物 |
| JPH0912574A (ja) * | 1995-06-28 | 1997-01-14 | Maruho Kk | 抗真菌剤 |
| AU2002253440A1 (en) * | 2002-04-12 | 2003-10-27 | Ranbaxy Laboratories Limited | Derivatives of 2,2,4-trisubstituted tetrahydrofuran as antifungal agents |
| JP2009286773A (ja) * | 2008-03-14 | 2009-12-10 | Bayer Cropscience Ag | 殺虫性縮環式アリール類 |
| CN104119322B (zh) * | 2014-07-11 | 2016-05-18 | 北京迪尔乐农业高新技术研发中心 | 一种用于杀菌的三唑类化合物及其制备方法和应用 |
| CN111848600B (zh) * | 2020-07-30 | 2021-12-07 | 沈阳药科大学 | 2,4,4-三取代二氢噁唑衍生物及其用途 |
-
2020
- 2020-07-30 CN CN202010749278.4A patent/CN111848600B/zh active Active
-
2021
- 2021-07-29 WO PCT/CN2021/109144 patent/WO2022022616A1/fr active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| CN111848600A (zh) | 2020-10-30 |
| WO2022022616A1 (fr) | 2022-02-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111848600B (zh) | 2,4,4-三取代二氢噁唑衍生物及其用途 | |
| KR101286499B1 (ko) | 신경치료용 아졸 화합물 | |
| ES2609803T3 (es) | Nuevos derivados de triazol antifúngicos | |
| CN107311995B (zh) | 三环异恶唑类衍生物及其制备方法和应用 | |
| WO2007012724A1 (fr) | Derives de 1 , 2 , 4-thiadiazole utiles comme antifongiques , compositions contenant ces composes et leurs utilisations | |
| CA2281875A1 (fr) | Composes de type azole, leur production et leur utilisation | |
| KR20140129030A (ko) | 캔디다증 및 아스퍼질러스 감염을 치료하기 위한 화합물 및 방법 | |
| US20060178415A1 (en) | Azole derivatives as antifungal agents | |
| RU2690161C1 (ru) | 3,5-Замещенные производные тиазолидин-2,4-диона, обладающие противомикробной активностью | |
| US20050131041A1 (en) | Azole derivatives as antifungal agents | |
| CN109485607B (zh) | β-唑类-苯基酮衍生物及其用途 | |
| JP5755244B2 (ja) | 抗真菌剤として使用するための第２級８−ヒドロキシキノリン−７−カルボキサミド誘導体 | |
| JP5755245B2 (ja) | 新規な第２級８−ヒドロキシキノリン−７−カルボキサミド誘導体 | |
| CN110950845B (zh) | 甲酰乙酰胺唑类衍生物及其用途 | |
| BG63872B1 (bg) | Азоли, съдържащи естери, с аминокиселини като противогъбични средства | |
| JP7061317B2 (ja) | アラニンおよびプロリンアミノ酸の機能的誘導体化合物およびそれを含む薬学的組成物 | |
| RU2662153C1 (ru) | Гибридные эфиры на основе производных тиазолидин-2,4-диона и азолов (1н-1,3-имидазола и 1н-1,3,4-триазола) и их применение | |
| CN115160250A (zh) | 4,6-联苯二酚类衍生物及其用途 | |
| JP2006515297A (ja) | シクロペンチル・グルタルアミド類と、中性エンドペプチダーゼ阻害剤としてのそれらの使用 | |
| US6710049B2 (en) | Azole compounds as anti-fungal agents | |
| CN116041330B (zh) | 一种含苯并氮杂环侧链的三氮唑醇类抗真菌化合物及其制备方法与用途 | |
| CN118515621A (zh) | 含有乙炔基的唑醇类化合物及其用途 | |
| RU2771027C1 (ru) | Гибридные производные (1Н-1,2,4) триазола и серосодержащих гетероциклов: производных тиазолидин-2,4-диона, тиоморфолин-3-она и 1,4-тиазепан-3-она, обладающих антимикробной активностью | |
| US20040242896A1 (en) | Azole compounds as anti-fungal agents | |
| KR100738228B1 (ko) | 아졸계 항균제 화합물 및 그의 제조방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |