DE69716925T2 - Isoxazoline derivate und ihre verwendung als antimikroben - Google Patents
Isoxazoline derivate und ihre verwendung als antimikrobenInfo
- Publication number
- DE69716925T2 DE69716925T2 DE69716925T DE69716925T DE69716925T2 DE 69716925 T2 DE69716925 T2 DE 69716925T2 DE 69716925 T DE69716925 T DE 69716925T DE 69716925 T DE69716925 T DE 69716925T DE 69716925 T2 DE69716925 T2 DE 69716925T2
- Authority
- DE
- Germany
- Prior art keywords
- dihydro
- methyl
- isoxazolyl
- acetamide
- phenyl
- 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.)
- Expired - Fee Related
Links
- 150000002547 isoxazolines Chemical class 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 64
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- -1 (±)-N-[[4,5-Dihydro-3-[4-[1-(4-oxo-2-thiadiazolinyl)-3,6-dihydro-2H-pyridin-4-yl]-3,5 -difluorophenyl]-5-isoxazolyl]methyl]acetamide Chemical compound 0.000 claims description 63
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical group 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- ZPNPRXYSBVYQRW-UHFFFAOYSA-N n-[[3-[4-(3,6-dihydro-2h-pyridin-1-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)N2CC=CCC2)=N1 ZPNPRXYSBVYQRW-UHFFFAOYSA-N 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- LGLMAJVQLRZTNE-UHFFFAOYSA-N tert-butyl 4-[4-[5-(acetamidomethyl)-4,5-dihydro-1,2-oxazol-3-yl]phenyl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C=2CCN(CC=2)C(=O)OC(C)(C)C)=N1 LGLMAJVQLRZTNE-UHFFFAOYSA-N 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical group O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- UZDQAKCZSLBAOL-QGZVFWFLSA-N n-[[(5r)-3-[4-[1-(2-hydroxyacetyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1[C@@H](CNC(=O)C)CC(C=2C=CC(=CC=2)C=2CCN(CC=2)C(=O)CO)=N1 UZDQAKCZSLBAOL-QGZVFWFLSA-N 0.000 claims description 4
- GTQULBMUHWIQCZ-UHFFFAOYSA-N n-[[3-[4-(1-acetyl-3,6-dihydro-2h-pyridin-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C=2CCN(CC=2)C(C)=O)=N1 GTQULBMUHWIQCZ-UHFFFAOYSA-N 0.000 claims description 4
- QWAWTNNQWBSDDT-UHFFFAOYSA-N n-[[3-[4-(4-methoxy-5-oxocyclohepta-1,3,6-trien-1-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound C1=CC(=O)C(OC)=CC=C1C1=CC=C(C=2CC(CNC(C)=O)ON=2)C=C1 QWAWTNNQWBSDDT-UHFFFAOYSA-N 0.000 claims description 4
- NRALJEUUKOLTFO-UHFFFAOYSA-N n-[[3-[4-(thian-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C2CCSCC2)=N1 NRALJEUUKOLTFO-UHFFFAOYSA-N 0.000 claims description 4
- UZDQAKCZSLBAOL-UHFFFAOYSA-N n-[[3-[4-[1-(2-hydroxyacetyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C=2CCN(CC=2)C(=O)CO)=N1 UZDQAKCZSLBAOL-UHFFFAOYSA-N 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- HRVZACOQSFRTKH-MRXNPFEDSA-N n-[[(5r)-3-(4-pyridin-4-ylphenyl)-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1[C@@H](CNC(=O)C)CC(C=2C=CC(=CC=2)C=2C=CN=CC=2)=N1 HRVZACOQSFRTKH-MRXNPFEDSA-N 0.000 claims description 3
- POXYVDFDXYIXRT-UHFFFAOYSA-N n-[[3-[3,5-difluoro-4-(thian-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C3CCSCC3)=C(F)C=2)=N1 POXYVDFDXYIXRT-UHFFFAOYSA-N 0.000 claims description 3
- IBLBWRVAOWITGU-UHFFFAOYSA-N n-[[3-[3-fluoro-4-(thian-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C3CCSCC3)=CC=2)=N1 IBLBWRVAOWITGU-UHFFFAOYSA-N 0.000 claims description 3
- PNJMIKJZKBMSSU-UHFFFAOYSA-N n-[[3-[4-(3,6-dihydro-2h-pyran-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C=2CCOCC=2)=N1 PNJMIKJZKBMSSU-UHFFFAOYSA-N 0.000 claims description 3
- BYSSENUPTFVDBR-UHFFFAOYSA-N n-[[3-[4-(3,6-dihydro-2h-thiopyran-4-yl)-3,5-difluorophenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C=3CCSCC=3)=C(F)C=2)=N1 BYSSENUPTFVDBR-UHFFFAOYSA-N 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- XDGXPUWESVCNHF-UHFFFAOYSA-N N-[[3-[3-fluoro-4-[1-(4-oxothiadiazol-5-yl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O=C1N=NSC1N1CCC(=CC1)C1=C(C=C(C=C1)C1=NOC(C1)CNC(C)=O)F XDGXPUWESVCNHF-UHFFFAOYSA-N 0.000 claims description 2
- NXXGWJQIEZFTKF-UHFFFAOYSA-N N-[[3-[3-fluoro-4-[1-(4-oxothiadiazol-5-yl)piperidin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O=C1N=NSC1N1CCC(CC1)C1=C(C=C(C=C1)C1=NOC(C1)CNC(C)=O)F NXXGWJQIEZFTKF-UHFFFAOYSA-N 0.000 claims description 2
- FGTHJJZHHHMURK-UHFFFAOYSA-N N-[[3-[4-[1-(4-oxothiadiazol-5-yl)-3,6-dihydro-2H-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O=C1N=NSC1N1CCC(=CC1)C1=CC=C(C=C1)C1=NOC(C1)CNC(C)=O FGTHJJZHHHMURK-UHFFFAOYSA-N 0.000 claims description 2
- NUNHLATUJOIOAI-UHFFFAOYSA-N N-[[3-[4-[1-(4-oxothiadiazol-5-yl)piperidin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O=C1N=NSC1N1CCC(CC1)C1=CC=C(C=C1)C1=NOC(C1)CNC(C)=O NUNHLATUJOIOAI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 230000000813 microbial effect Effects 0.000 claims description 2
- JIFUJSOILXJUCP-UHFFFAOYSA-N n-[[3-[3,5-difluoro-4-(4-methoxy-5-oxocyclohepta-1,3,6-trien-1-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound C1=CC(=O)C(OC)=CC=C1C1=C(F)C=C(C=2CC(CNC(C)=O)ON=2)C=C1F JIFUJSOILXJUCP-UHFFFAOYSA-N 0.000 claims description 2
- BUALKJBTSMBMMS-UHFFFAOYSA-N n-[[3-[3,5-difluoro-4-[1-(2-hydroxyacetyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C=3CCN(CC=3)C(=O)CO)=C(F)C=2)=N1 BUALKJBTSMBMMS-UHFFFAOYSA-N 0.000 claims description 2
- LYICOQOSBQRDGX-UHFFFAOYSA-N n-[[3-[3,5-difluoro-4-[1-(2-hydroxyacetyl)piperidin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C3CCN(CC3)C(=O)CO)=C(F)C=2)=N1 LYICOQOSBQRDGX-UHFFFAOYSA-N 0.000 claims description 2
- BGTAJQSYNKLJQY-UHFFFAOYSA-N n-[[3-[3,5-difluoro-4-[1-(5-methyl-1,3,4-thiadiazol-2-yl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C=3CCN(CC=3)C=3SC(C)=NN=3)=C(F)C=2)=N1 BGTAJQSYNKLJQY-UHFFFAOYSA-N 0.000 claims description 2
- JJZSPKWKDZNLKX-UHFFFAOYSA-N n-[[3-[3,5-difluoro-4-[1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C3CCN(CC3)C=3SC(C)=NN=3)=C(F)C=2)=N1 JJZSPKWKDZNLKX-UHFFFAOYSA-N 0.000 claims description 2
- FBQRNEPVACMDRS-UHFFFAOYSA-N n-[[3-[3-fluoro-4-(4-methoxy-5-oxocyclohepta-1,3,6-trien-1-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound C1=CC(=O)C(OC)=CC=C1C1=CC=C(C=2CC(CNC(C)=O)ON=2)C=C1F FBQRNEPVACMDRS-UHFFFAOYSA-N 0.000 claims description 2
- ZDALXWVBHZTTFU-UHFFFAOYSA-N n-[[3-[3-fluoro-4-(oxan-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C3CCOCC3)=CC=2)=N1 ZDALXWVBHZTTFU-UHFFFAOYSA-N 0.000 claims description 2
- ICEQPDLVSZXHHS-UHFFFAOYSA-N n-[[3-[3-fluoro-4-[1-(2-hydroxyacetyl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C=3CCN(CC=3)C(=O)CO)=CC=2)=N1 ICEQPDLVSZXHHS-UHFFFAOYSA-N 0.000 claims description 2
- ARCMSUCTQZNZAG-UHFFFAOYSA-N n-[[3-[3-fluoro-4-[1-(2-hydroxyacetyl)piperidin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C3CCN(CC3)C(=O)CO)=CC=2)=N1 ARCMSUCTQZNZAG-UHFFFAOYSA-N 0.000 claims description 2
- POSFVJGLSTWABU-UHFFFAOYSA-N n-[[3-[3-fluoro-4-[1-(5-methyl-1,3,4-thiadiazol-2-yl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C=3CCN(CC=3)C=3SC(C)=NN=3)=CC=2)=N1 POSFVJGLSTWABU-UHFFFAOYSA-N 0.000 claims description 2
- OEXFVQLHZUBTAL-UHFFFAOYSA-N n-[[3-[3-fluoro-4-[1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C3CCN(CC3)C=3SC(C)=NN=3)=CC=2)=N1 OEXFVQLHZUBTAL-UHFFFAOYSA-N 0.000 claims description 2
- IPZWKWFRYSNTRN-UHFFFAOYSA-N n-[[3-[4-(3,6-dihydro-2h-pyran-4-yl)-3,5-difluorophenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C=3CCOCC=3)=C(F)C=2)=N1 IPZWKWFRYSNTRN-UHFFFAOYSA-N 0.000 claims description 2
- ZWLBGPZGRAMCHK-UHFFFAOYSA-N n-[[3-[4-(3,6-dihydro-2h-pyran-4-yl)-3-fluorophenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C=3CCOCC=3)=CC=2)=N1 ZWLBGPZGRAMCHK-UHFFFAOYSA-N 0.000 claims description 2
- OJTAGZBBXMFKEK-UHFFFAOYSA-N n-[[3-[4-(3,6-dihydro-2h-thiopyran-4-yl)-3-fluorophenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C=3CCSCC=3)=CC=2)=N1 OJTAGZBBXMFKEK-UHFFFAOYSA-N 0.000 claims description 2
- OFLKFKZIUYCCSD-UHFFFAOYSA-N n-[[3-[4-(3,6-dihydro-2h-thiopyran-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C=2CCSCC=2)=N1 OFLKFKZIUYCCSD-UHFFFAOYSA-N 0.000 claims description 2
- BMSAYUZOKUITAF-UHFFFAOYSA-N n-[[3-[4-(oxan-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C2CCOCC2)=N1 BMSAYUZOKUITAF-UHFFFAOYSA-N 0.000 claims description 2
- HARZNABJYQHOBT-UHFFFAOYSA-N n-[[3-[4-[1-(2-hydroxyacetyl)piperidin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C2CCN(CC2)C(=O)CO)=N1 HARZNABJYQHOBT-UHFFFAOYSA-N 0.000 claims description 2
- YRUDDYNHKFKTTL-UHFFFAOYSA-N n-[[3-[4-[1-(5-methyl-1,3,4-thiadiazol-2-yl)-3,6-dihydro-2h-pyridin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C=2CCN(CC=2)C=2SC(C)=NN=2)=N1 YRUDDYNHKFKTTL-UHFFFAOYSA-N 0.000 claims description 2
- KFITZXAUVFBIGM-UHFFFAOYSA-N n-[[3-[4-[1-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C2CCN(CC2)C=2SC(C)=NN=2)=N1 KFITZXAUVFBIGM-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 238000000034 method Methods 0.000 description 24
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 19
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 11
- 150000002825 nitriles Chemical class 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 6
- 239000008194 pharmaceutical composition Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- 241000186367 Mycobacterium avium Species 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 150000001336 alkenes Chemical class 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 239000004599 antimicrobial Substances 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 244000052769 pathogen Species 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical class C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 3
- 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 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 125000005228 aryl sulfonate group Chemical group 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 239000003054 catalyst Substances 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
- 238000007796 conventional method Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 3
- 239000001974 tryptic soy broth Substances 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
- FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 241000606125 Bacteroides Species 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 241001112696 Clostridia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 241000295644 Staphylococcaceae Species 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-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
- QPTIGFZECTYUGC-UHFFFAOYSA-N [3-(4-pyridin-4-ylphenyl)-1,2-oxazol-5-yl]methanamine Chemical compound O1C(CN)=CC(C=2C=CC(=CC=2)C=2C=CN=CC=2)=N1 QPTIGFZECTYUGC-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000008052 alkyl sulfonates Chemical class 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- CDAISMWEOUEBRE-UHFFFAOYSA-N inositol Chemical compound OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000003971 isoxazolinyl group Chemical group 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- SIMWTRCFFSTNMG-AWEZNQCLSA-N n-[[(5s)-3-[3-fluoro-4-[4-(2-hydroxyacetyl)piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CO)CC1 SIMWTRCFFSTNMG-AWEZNQCLSA-N 0.000 description 2
- PVEHHMPFRIYOQZ-UHFFFAOYSA-N n-[[3-(4-bromophenyl)-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(Br)=CC=2)=N1 PVEHHMPFRIYOQZ-UHFFFAOYSA-N 0.000 description 2
- GSDJEQKAFUBQFV-UHFFFAOYSA-N n-[[3-(4-trimethylstannylphenyl)-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)[Sn](C)(C)C)=N1 GSDJEQKAFUBQFV-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- LYGJENNIWJXYER-BJUDXGSMSA-N nitromethane Chemical class [11CH3][N+]([O-])=O LYGJENNIWJXYER-BJUDXGSMSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-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
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- YCBWXJZXFUKDPU-UHFFFAOYSA-N trimethyl(pyridin-4-yl)stannane Chemical compound C[Sn](C)(C)C1=CC=NC=C1 YCBWXJZXFUKDPU-UHFFFAOYSA-N 0.000 description 2
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 2
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 2
- 108010050327 trypticase-soy broth Proteins 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 1
- HZDNNJABYXNPPV-UHFFFAOYSA-N (2-chloro-2-oxoethyl) acetate Chemical compound CC(=O)OCC(Cl)=O HZDNNJABYXNPPV-UHFFFAOYSA-N 0.000 description 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 1
- 125000004505 1,2,4-oxadiazol-5-yl group Chemical group O1N=CN=C1* 0.000 description 1
- BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 1
- 125000004515 1,2,4-thiadiazol-3-yl group Chemical group S1N=C(N=C1)* 0.000 description 1
- 125000004516 1,2,4-thiadiazol-5-yl group Chemical group S1N=CN=C1* 0.000 description 1
- 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
- 125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
- 125000001414 1,2,4-triazol-5-yl group Chemical group [H]N1N=C([H])N=C1[*] 0.000 description 1
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
- 125000004522 1,3,4-thiadiazol-5-yl group Chemical group S1C=NN=C1* 0.000 description 1
- AZWHPGZNOIYGFB-UHFFFAOYSA-N 1,3,5-trimethylcyclohexane-1,3,5-tricarboxylic acid Chemical compound OC(=O)C1(C)CC(C)(C(O)=O)CC(C)(C(O)=O)C1 AZWHPGZNOIYGFB-UHFFFAOYSA-N 0.000 description 1
- 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 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- QXMJAMBPNHRAPD-UHFFFAOYSA-N 1-oxido-3h-oxathiazol-1-ium Chemical compound [O-][O+]1SNC=C1 QXMJAMBPNHRAPD-UHFFFAOYSA-N 0.000 description 1
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical group C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- IVHKZCSZELZKSJ-UHFFFAOYSA-N 2-hydroxyethyl sulfonate Chemical compound OCCOS(=O)=O IVHKZCSZELZKSJ-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- MWWNNNAOGWPTQY-UHFFFAOYSA-N 3-nitrobenzenesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=CC(S(Cl)(=O)=O)=C1 MWWNNNAOGWPTQY-UHFFFAOYSA-N 0.000 description 1
- NCTCGHLIHJJIBK-UHFFFAOYSA-N 3-phenyl-1,3-oxazolidin-2-one Chemical class O=C1OCCN1C1=CC=CC=C1 NCTCGHLIHJJIBK-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- QWSQNLKNOPXCKY-UHFFFAOYSA-N 3h-1,2,4-dithiazole 1-oxide Chemical compound O=S1SCN=C1 QWSQNLKNOPXCKY-UHFFFAOYSA-N 0.000 description 1
- CHPTUAHBVDCEPL-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazol-5-ylmethanamine Chemical compound NCC1CC=NO1 CHPTUAHBVDCEPL-UHFFFAOYSA-N 0.000 description 1
- PHVFVPURCHVDBP-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazol-5-ylmethanol Chemical class OCC1CC=NO1 PHVFVPURCHVDBP-UHFFFAOYSA-N 0.000 description 1
- ZOPFQZFNZNMZEF-UHFFFAOYSA-N 4-bromo-n-hydroxybenzenecarboximidoyl chloride Chemical compound ON=C(Cl)C1=CC=C(Br)C=C1 ZOPFQZFNZNMZEF-UHFFFAOYSA-N 0.000 description 1
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
- ZRDLQVIEHKAGPA-UHFFFAOYSA-N 5-(azidomethyl)-4,5-dihydro-1,2-oxazole Chemical compound [N-]=[N+]=NCC1CC=NO1 ZRDLQVIEHKAGPA-UHFFFAOYSA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000194032 Enterococcus faecalis Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 206010061217 Infestation Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 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 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- WXTVTJMZFUSBCG-UHFFFAOYSA-N N-[[3-[4-[1-(2-hydroxyacetyl)-2,3,6,7-tetrahydroazepin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=CC(=CC=2)C=2CCN(CCC=2)C(=O)CO)=N1 WXTVTJMZFUSBCG-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- VVBXKASDRZXWON-UHFFFAOYSA-N N=[PH3] Chemical compound N=[PH3] VVBXKASDRZXWON-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000233614 Phytophthora Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 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
- 108010059993 Vancomycin Proteins 0.000 description 1
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 241001148470 aerobic bacillus Species 0.000 description 1
- 238000002814 agar dilution Methods 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000007478 blood agar base Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- MYPYJXKWCTUITO-KIIOPKALSA-N chembl3301825 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(O)[C@H](C)O1 MYPYJXKWCTUITO-KIIOPKALSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006352 cycloaddition reaction Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000002704 decyl 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])C([H])([H])C([H])([H])* 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- HQWPLXHWEZZGKY-UHFFFAOYSA-N diethylzinc Chemical compound CC[Zn]CC HQWPLXHWEZZGKY-UHFFFAOYSA-N 0.000 description 1
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 125000003438 dodecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 229940032049 enterococcus faecalis Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 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
- 150000002390 heteroarenes Chemical class 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
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- CBEQRNSPHCCXSH-UHFFFAOYSA-N iodine monobromide Chemical compound IBr CBEQRNSPHCCXSH-UHFFFAOYSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical compound [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 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
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 125000001421 myristyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZPNPRXYSBVYQRW-MRXNPFEDSA-N n-[[(5r)-3-[4-(3,6-dihydro-2h-pyridin-1-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1[C@@H](CNC(=O)C)CC(C=2C=CC(=CC=2)N2CC=CCC2)=N1 ZPNPRXYSBVYQRW-MRXNPFEDSA-N 0.000 description 1
- CIDMLMSQKFERPR-UHFFFAOYSA-N n-[[3-[3,5-difluoro-4-(oxan-4-yl)phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(C3CCOCC3)=C(F)C=2)=N1 CIDMLMSQKFERPR-UHFFFAOYSA-N 0.000 description 1
- AXQOAGTVCXXTKY-UHFFFAOYSA-N n-[[3-[3,5-difluoro-4-[1-(2-hydroxyacetyl)-2,3,6,7-tetrahydroazepin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(=C(F)C=2)C=2CCN(CCC=2)C(=O)CO)=N1 AXQOAGTVCXXTKY-UHFFFAOYSA-N 0.000 description 1
- LFHLJXIEHQXGEF-UHFFFAOYSA-N n-[[3-[3-fluoro-4-[1-(2-hydroxyacetyl)-2,3,6,7-tetrahydroazepin-4-yl]phenyl]-4,5-dihydro-1,2-oxazol-5-yl]methyl]acetamide Chemical compound O1C(CNC(=O)C)CC(C=2C=C(F)C(=CC=2)C=2CCN(CCC=2)C(=O)CO)=N1 LFHLJXIEHQXGEF-UHFFFAOYSA-N 0.000 description 1
- VLZLOWPYUQHHCG-UHFFFAOYSA-N nitromethylbenzene Chemical compound [O-][N+](=O)CC1=CC=CC=C1 VLZLOWPYUQHHCG-UHFFFAOYSA-N 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- 125000001400 nonyl 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])C([H])([H])[H] 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
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000012071 phase Substances 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
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical group C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 229910000080 stannane Inorganic materials 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- YGNGABUJMXJPIJ-UHFFFAOYSA-N thiatriazole Chemical compound C1=NN=NS1 YGNGABUJMXJPIJ-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 229930192474 thiophene Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 125000002889 tridecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- QVWDCTQRORVHHT-UHFFFAOYSA-N tropone Chemical group O=C1C=CC=CC=C1 QVWDCTQRORVHHT-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl 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])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 239000008215 water for injection Substances 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
- C07D413/10—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 aromatic rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2428796P | 1996-08-21 | 1996-08-21 | |
| PCT/US1997/013934 WO1998007708A1 (en) | 1996-08-21 | 1997-08-15 | Isoxazoline derivatives useful as antimicrobials |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69716925D1 DE69716925D1 (de) | 2002-12-12 |
| DE69716925T2 true DE69716925T2 (de) | 2003-09-11 |
Family
ID=21819822
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69716925T Expired - Fee Related DE69716925T2 (de) | 1996-08-21 | 1997-08-15 | Isoxazoline derivate und ihre verwendung als antimikroben |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US5990136A (OSRAM) |
| EP (1) | EP0920421B1 (OSRAM) |
| JP (1) | JP2000516245A (OSRAM) |
| AT (1) | ATE227277T1 (OSRAM) |
| AU (1) | AU3973697A (OSRAM) |
| DE (1) | DE69716925T2 (OSRAM) |
| DK (1) | DK0920421T3 (OSRAM) |
| ES (1) | ES2186916T3 (OSRAM) |
| PT (1) | PT920421E (OSRAM) |
| WO (1) | WO1998007708A1 (OSRAM) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9601666D0 (en) * | 1996-01-27 | 1996-03-27 | Zeneca Ltd | Chemical compounds |
| GB9609919D0 (en) * | 1996-05-11 | 1996-07-17 | Zeneca Ltd | Chemical compounds |
| RU2208613C2 (ru) | 1997-05-30 | 2003-07-20 | Фармация Энд Апджон Компани | Оксазолидиноновые антибактериальные агенты, содержащие тиокарбонильную функциональную группу |
| US6255304B1 (en) | 1997-05-30 | 2001-07-03 | Pharmacia & Upjohn Company | Oxazolidinone antibacterial agents having a thiocarbonyl functionality |
| GB9717807D0 (en) | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
| GB9717804D0 (en) | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
| GB9725244D0 (en) | 1997-11-29 | 1998-01-28 | Zeneca Ltd | Chemical compounds |
| DE69902634T2 (de) * | 1998-02-13 | 2003-04-24 | Pharmacia & Upjohn Co., Kalamazoo | Substituierte aminophenylisoxazolinderivate verwendbar als antimikrobielle agenzien |
| CA2318762A1 (en) * | 1998-02-25 | 1999-09-02 | Richard Charles Thomas | Substituted aminomethyl isoxazoline derivatives useful as antimicrobials |
| CA2333332A1 (en) | 1998-06-05 | 1999-12-16 | Astrazeneca Ab | Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them |
| US6420349B1 (en) | 1998-08-24 | 2002-07-16 | Bristol-Myers Squibb Company | Isoxazolinone antibacterial agents |
| TW572757B (en) * | 1998-08-24 | 2004-01-21 | Bristol Myers Squibb Co | Novel isoxazolinone antibacterial agents |
| GB9928568D0 (en) | 1999-12-03 | 2000-02-02 | Zeneca Ltd | Chemical compounds |
| GB0009803D0 (en) | 2000-04-25 | 2000-06-07 | Astrazeneca Ab | Chemical compounds |
| US6465456B2 (en) | 2000-06-29 | 2002-10-15 | Bristol-Myers Squibb Company | Isoxazolinone antibacterial agents |
| ES2256331T3 (es) | 2000-12-21 | 2006-07-16 | PHARMACIA & UPJOHN COMPANY LLC | Derivados de quinolina antimicrobianos y uso de los mismos para tratar infecciones bacterianas. |
| JPWO2002053523A1 (ja) * | 2000-12-26 | 2004-04-30 | 財団法人乙卯研究所 | トロポロン誘導体 |
| US7022705B2 (en) | 2001-10-25 | 2006-04-04 | Astrazeneca Ab | Isoxazoline derivatives useful as antimicrobials |
| AR038536A1 (es) * | 2002-02-25 | 2005-01-19 | Upjohn Co | N-aril-2-oxazolidinona-5- carboxamidas y sus derivados |
| US7141588B2 (en) * | 2002-02-25 | 2006-11-28 | Pfizer, Inc. | N-aryl-2-oxazolidinone-5-carboxamides and their derivatives |
| WO2004069832A2 (en) * | 2003-02-07 | 2004-08-19 | Warner-Lambert Company Llc | Antibacterial agents |
| JP2006516989A (ja) * | 2003-02-07 | 2006-07-13 | ワーナー−ランバート・カンパニー、リミテッド、ライアビリティ、カンパニー | 抗菌剤として使用するための二環式環によりｎ−置換されたオキサゾリジノン誘導体 |
| US7304050B2 (en) * | 2003-09-16 | 2007-12-04 | Pfizer Inc. | Antibacterial agents |
| WO2005082900A2 (en) * | 2004-01-28 | 2005-09-09 | Pharmacia & Upjohn Company Llc | Oxazolidinone amidoximes as antibacterial agents |
| EP1781643A1 (en) * | 2004-08-06 | 2007-05-09 | Pharmacia & Upjohn Company LLC | Oxindole oxazolidinones as antibacterial agents |
| RU2392273C2 (ru) * | 2004-09-10 | 2010-06-20 | Синджента Лимитед | Замещенные изоксазолы в качестве фунгицидов |
| PH12013500164A1 (en) * | 2010-08-05 | 2015-07-08 | Zoetis Services Llc | Isoxazoline derivatives as antiparasitic agents |
| CA2822357A1 (en) | 2010-12-22 | 2012-06-28 | Abbvie Inc. | Hepatitis c inhibitors and uses thereof |
| AU2013327663B2 (en) * | 2012-10-03 | 2016-03-10 | Shell Internationale Research Maatschappij B.V. | Optimizing performance of a drilling assembly |
| WO2021000297A1 (en) | 2019-07-03 | 2021-01-07 | Merck Sharp & Dohme Corp. | Compounds and methods of use thereof as antibacterial agents |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL137326C (OSRAM) * | 1967-08-26 | |||
| US4283403A (en) * | 1976-06-14 | 1981-08-11 | Eli Lilly And Company | Substituted isoxazolines for control of plant phytopathogens |
| US4948801A (en) * | 1988-07-29 | 1990-08-14 | E. I. Du Pont De Nemours And Company | Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents |
| CZ288788B6 (cs) * | 1992-12-08 | 2001-09-12 | Pharmacia & Upjohn Company | Antibakteriální fenyloxazolidinony substituované troponem |
| DE69422061T2 (de) * | 1993-11-26 | 2000-03-30 | Pfizer, Inc. | 3-phenyl-2-isoxazoline derivate als entzündugshemmende mittel |
| DE4425612A1 (de) * | 1994-07-20 | 1996-04-04 | Bayer Ag | 6-gliedrige stickstoffhaltige Heteroaryl-oxazolidinone |
| DE4425613A1 (de) * | 1994-07-20 | 1996-01-25 | Bayer Ag | 5-gliedrige Heteroaryl-oxazolidinone |
| US5710159A (en) * | 1996-05-09 | 1998-01-20 | The Dupont Merck Pharmaceutical Company | Integrin receptor antagonists |
-
1997
- 1997-08-15 AT AT97937156T patent/ATE227277T1/de not_active IP Right Cessation
- 1997-08-15 JP JP10510781A patent/JP2000516245A/ja not_active Withdrawn
- 1997-08-15 AU AU39736/97A patent/AU3973697A/en not_active Abandoned
- 1997-08-15 PT PT97937156T patent/PT920421E/pt unknown
- 1997-08-15 DE DE69716925T patent/DE69716925T2/de not_active Expired - Fee Related
- 1997-08-15 EP EP97937156A patent/EP0920421B1/en not_active Expired - Lifetime
- 1997-08-15 US US08/999,753 patent/US5990136A/en not_active Expired - Fee Related
- 1997-08-15 WO PCT/US1997/013934 patent/WO1998007708A1/en not_active Ceased
- 1997-08-15 ES ES97937156T patent/ES2186916T3/es not_active Expired - Lifetime
- 1997-08-15 DK DK97937156T patent/DK0920421T3/da active
-
1999
- 1999-08-31 US US09/386,647 patent/US6093736A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US6093736A (en) | 2000-07-25 |
| EP0920421B1 (en) | 2002-11-06 |
| AU3973697A (en) | 1998-03-06 |
| DK0920421T3 (da) | 2003-03-10 |
| JP2000516245A (ja) | 2000-12-05 |
| WO1998007708A1 (en) | 1998-02-26 |
| DE69716925D1 (de) | 2002-12-12 |
| ATE227277T1 (de) | 2002-11-15 |
| PT920421E (pt) | 2003-03-31 |
| US5990136A (en) | 1999-11-23 |
| ES2186916T3 (es) | 2003-05-16 |
| EP0920421A1 (en) | 1999-06-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69716925T2 (de) | Isoxazoline derivate und ihre verwendung als antimikroben | |
| DE69902634T2 (de) | Substituierte aminophenylisoxazolinderivate verwendbar als antimikrobielle agenzien | |
| DE60205030T2 (de) | Oxazolidinon- und/oder isoxazolinderivate als antibakterielle mittel | |
| US6365751B1 (en) | Antibiotic oxazolidinone derivatives | |
| DE69829846T2 (de) | Antibakteriell wirksam oxazolidinone mit einer thiocarbonylfunktionalität | |
| DE69632074T2 (de) | Oxazolidinone mit tricyclische substituente als antibacterielle mittel | |
| DE69616366T2 (de) | Phenyloxazolidinone mit einer c-c-bindung zu 4-8 gliedrigen heterocyclen | |
| DE60210654T2 (de) | Aryl substituierte oxazolidinone mit antibacterieller activität | |
| DE60212959T2 (de) | Eine sulfonimid-gruppe enthaltende oxazolidinone als antibiotika | |
| DE69717630T2 (de) | 3-phenyl-furan-(5h)-2-on- und dihydrofuran-2-on-derivate als antibakterielle mittel | |
| DE60222645T2 (de) | Verfahren zur herstellung von oxazolidinonen | |
| DE60206154T2 (de) | Bicyclo[3,1,0]hexan als strukturelement enthaltende oxazolidinon-antibiotika und deren derivate | |
| US6281210B1 (en) | Benzoic acid esters of oxazolidinones having a hydroxyacetylpiperazine substituent | |
| US20040014967A1 (en) | Amide-containing compound having improved solubility and method of improving the solubility of an amide-containing compound | |
| US7279494B2 (en) | Antimicrobial [3.1.0] bicyclohexylphenyl-oxazolidinone derivatives and analogues | |
| CA2501352A1 (en) | Antimicrobial [3.1.0] bicyclic oxazolidinone derivatives | |
| DE60304360T2 (de) | N-aryl-2-oxazolidinone und deren derivate | |
| US6825225B2 (en) | Bicyclic isoxazolinones as antibacterial agents | |
| EP1660488A1 (en) | Novel antimicrobial aryloxazolidinone compounds |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |