CA2507468A1 - Oxazolidinone and / or isoxazoline derivatives as antibacterial agents - Google Patents
Oxazolidinone and / or isoxazoline derivatives as antibacterial agents Download PDFInfo
- Publication number
- CA2507468A1 CA2507468A1 CA002507468A CA2507468A CA2507468A1 CA 2507468 A1 CA2507468 A1 CA 2507468A1 CA 002507468 A CA002507468 A CA 002507468A CA 2507468 A CA2507468 A CA 2507468A CA 2507468 A1 CA2507468 A1 CA 2507468A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- ring
- alkoxy
- group
- optionally substituted
- 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.)
- Abandoned
Links
- 239000003242 anti bacterial agent Substances 0.000 title claims abstract description 15
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 title claims description 39
- 150000002547 isoxazolines Chemical class 0.000 title description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 498
- 150000001875 compounds Chemical class 0.000 claims abstract description 263
- 150000002148 esters Chemical class 0.000 claims abstract description 142
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 136
- 150000003839 salts Chemical class 0.000 claims abstract description 132
- 239000000203 mixture Substances 0.000 claims abstract description 127
- 238000001727 in vivo Methods 0.000 claims abstract description 122
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 85
- 238000000034 method Methods 0.000 claims abstract description 57
- -1 cyano, carboxy Chemical group 0.000 claims description 333
- 125000001424 substituent group Chemical group 0.000 claims description 147
- 125000003545 alkoxy group Chemical group 0.000 claims description 142
- 239000001257 hydrogen Substances 0.000 claims description 98
- 229910052757 nitrogen Inorganic materials 0.000 claims description 80
- 229910052799 carbon Inorganic materials 0.000 claims description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 53
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 52
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 50
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 50
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 43
- 125000005843 halogen group Chemical group 0.000 claims description 43
- 150000001721 carbon Chemical group 0.000 claims description 40
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 40
- 150000002431 hydrogen Chemical group 0.000 claims description 40
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- 229910052717 sulfur Inorganic materials 0.000 claims description 34
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 33
- 125000003971 isoxazolinyl group Chemical group 0.000 claims description 33
- 229910052760 oxygen Inorganic materials 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 31
- 125000003282 alkyl amino group Chemical group 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 30
- 125000002252 acyl group Chemical group 0.000 claims description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 29
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 28
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 28
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 26
- 125000000304 alkynyl group Chemical group 0.000 claims description 26
- 125000003342 alkenyl group Chemical group 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 230000008569 process Effects 0.000 claims description 22
- 239000000651 prodrug Substances 0.000 claims description 21
- 229940002612 prodrug Drugs 0.000 claims description 21
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 21
- 229910052801 chlorine Inorganic materials 0.000 claims description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 19
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 125000006239 protecting group Chemical group 0.000 claims description 19
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 16
- 125000004414 alkyl thio group Chemical group 0.000 claims description 16
- 230000000844 anti-bacterial effect Effects 0.000 claims description 15
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 15
- 125000002534 ethynyl group Chemical class [H]C#C* 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 15
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 238000005859 coupling reaction Methods 0.000 claims description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 230000008878 coupling Effects 0.000 claims description 11
- 238000010168 coupling process Methods 0.000 claims description 11
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 11
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 9
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 9
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical group C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 8
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 7
- 125000005418 aryl aryl group Chemical group 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 241000894006 Bacteria Species 0.000 claims description 6
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 150000001540 azides Chemical class 0.000 claims description 6
- 125000001475 halogen functional group Chemical group 0.000 claims description 6
- 150000002825 nitriles Chemical class 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 claims description 5
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 229910052723 transition metal Inorganic materials 0.000 claims description 5
- 150000003624 transition metals Chemical class 0.000 claims description 5
- 150000003852 triazoles Chemical class 0.000 claims description 5
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 4
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
- 102220024746 rs199473444 Human genes 0.000 claims description 4
- DVSMAFFYUWLENL-UHFFFAOYSA-N 3-(azidomethyl)-1,3-oxazolidin-2-one Chemical class [N-]=[N+]=NCN1CCOC1=O DVSMAFFYUWLENL-UHFFFAOYSA-N 0.000 claims description 3
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 3
- 241000192125 Firmicutes Species 0.000 claims description 3
- 125000006323 alkenyl amino group Chemical group 0.000 claims description 3
- 238000006352 cycloaddition reaction Methods 0.000 claims description 3
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 3
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 3
- 239000003701 inert diluent Substances 0.000 claims description 3
- 150000002923 oximes Chemical class 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- 229940088594 vitamin Drugs 0.000 claims description 3
- 229930003231 vitamin Natural products 0.000 claims description 3
- 235000013343 vitamin Nutrition 0.000 claims description 3
- 239000011782 vitamin Substances 0.000 claims description 3
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 3
- NVZIFMAZKAYQJR-UHFFFAOYSA-N 3-(aminomethyl)-1,3-oxazolidin-2-one Chemical class NCN1CCOC1=O NVZIFMAZKAYQJR-UHFFFAOYSA-N 0.000 claims description 2
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 claims description 2
- 229930003270 Vitamin B Natural products 0.000 claims description 2
- 125000000676 alkoxyimino group Chemical group 0.000 claims description 2
- 125000005742 alkyl ethenyl group Chemical group 0.000 claims description 2
- 125000005841 biaryl group Chemical group 0.000 claims description 2
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 150000001805 chlorine compounds Chemical class 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 239000012948 isocyanate Substances 0.000 claims description 2
- 150000002513 isocyanates Chemical class 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 2
- 150000002924 oxiranes Chemical class 0.000 claims description 2
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 claims description 2
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 238000005956 quaternization reaction Methods 0.000 claims description 2
- 239000012048 reactive intermediate Substances 0.000 claims description 2
- 125000003003 spiro group Chemical group 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- 235000019156 vitamin B Nutrition 0.000 claims description 2
- 239000011720 vitamin B Substances 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
- 150000000177 1,2,3-triazoles Chemical class 0.000 claims 2
- 150000001345 alkine derivatives Chemical group 0.000 claims 1
- XSXHWVKGUXMUQE-UHFFFAOYSA-N osmium dioxide Inorganic materials O=[Os]=O XSXHWVKGUXMUQE-UHFFFAOYSA-N 0.000 claims 1
- 125000000842 isoxazolyl group Chemical group 0.000 abstract description 18
- 125000003831 tetrazolyl group Chemical group 0.000 abstract description 2
- 125000001425 triazolyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 330
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 226
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 148
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 115
- 235000019439 ethyl acetate Nutrition 0.000 description 112
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 112
- 229940093499 ethyl acetate Drugs 0.000 description 107
- 229910001868 water Inorganic materials 0.000 description 107
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 102
- 239000007787 solid Substances 0.000 description 99
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 92
- 239000000243 solution Substances 0.000 description 90
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 55
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- 238000005160 1H NMR spectroscopy Methods 0.000 description 50
- 239000000741 silica gel Substances 0.000 description 48
- 229910002027 silica gel Inorganic materials 0.000 description 48
- 229960001866 silicon dioxide Drugs 0.000 description 48
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- 239000000047 product Substances 0.000 description 42
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 39
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
- 238000005481 NMR spectroscopy Methods 0.000 description 38
- 239000000543 intermediate Substances 0.000 description 37
- 239000003921 oil Substances 0.000 description 35
- 235000019198 oils Nutrition 0.000 description 35
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 34
- 239000011737 fluorine Substances 0.000 description 34
- 229910052938 sodium sulfate Inorganic materials 0.000 description 34
- 235000011152 sodium sulphate Nutrition 0.000 description 34
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 26
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 25
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 25
- 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 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 23
- 238000003818 flash chromatography Methods 0.000 description 22
- 239000012074 organic phase Substances 0.000 description 22
- 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 19
- 238000003756 stirring Methods 0.000 description 19
- AEIWZPGDBVWDTI-LYKKTTPLSA-N (5r)-3-[3-fluoro-4-[6-[5-(hydroxymethyl)-4,5-dihydro-1,2-oxazol-3-yl]pyridin-3-yl]phenyl]-5-(triazol-1-ylmethyl)-1,3-oxazolidin-2-one Chemical compound O1C(CO)CC(C=2N=CC(=CC=2)C=2C(=CC(=CC=2)N2C(O[C@@H](CN3N=NC=C3)C2)=O)F)=N1 AEIWZPGDBVWDTI-LYKKTTPLSA-N 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 235000019341 magnesium sulphate Nutrition 0.000 description 18
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 17
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 17
- 239000000460 chlorine Substances 0.000 description 17
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 16
- 238000004587 chromatography analysis Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 238000004440 column chromatography Methods 0.000 description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 15
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 15
- 125000001786 isothiazolyl group Chemical group 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 238000010828 elution Methods 0.000 description 14
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 14
- 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 14
- 238000001704 evaporation Methods 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 125000005997 bromomethyl group Chemical group 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
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- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 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 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 229940082632 vitamin b12 and folic acid Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000010626 work up procedure 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
- C07D413/14—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
-
- 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
- A61P31/04—Antibacterial agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6527—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and oxygen atoms as the only ring hetero atoms
- C07F9/653—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Medicinal Chemistry (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)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0227702.8 | 2002-11-28 | ||
| GB0227702A GB0227702D0 (en) | 2002-11-28 | 2002-11-28 | Chemical compounds |
| GB0304725.5 | 2003-03-01 | ||
| GB0304725A GB0304725D0 (en) | 2003-03-01 | 2003-03-01 | Chemical compounds |
| GB0318608A GB0318608D0 (en) | 2003-08-08 | 2003-08-08 | Chemical compounds |
| GB0318608.7 | 2003-08-08 | ||
| PCT/GB2003/005087 WO2004048392A1 (en) | 2002-11-28 | 2003-11-24 | Oxazolidinone and / or isoxazoline derivatives as antibacterial agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2507468A1 true CA2507468A1 (en) | 2004-06-10 |
Family
ID=32397650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002507468A Abandoned CA2507468A1 (en) | 2002-11-28 | 2003-11-24 | Oxazolidinone and / or isoxazoline derivatives as antibacterial agents |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US20060116400A1 (enExample) |
| EP (1) | EP1567532A1 (enExample) |
| JP (1) | JP2006508192A (enExample) |
| KR (1) | KR20050085193A (enExample) |
| AU (1) | AU2003302404B2 (enExample) |
| BR (1) | BR0316688A (enExample) |
| CA (1) | CA2507468A1 (enExample) |
| HK (1) | HK1079794A1 (enExample) |
| IL (1) | IL168747A0 (enExample) |
| MX (1) | MXPA05005651A (enExample) |
| NO (1) | NO20052534L (enExample) |
| NZ (1) | NZ540147A (enExample) |
| SA (1) | SA04250088A (enExample) |
| TW (1) | TW200533666A (enExample) |
| WO (1) | WO2004048392A1 (enExample) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR0212458A (pt) * | 2001-09-11 | 2004-10-19 | Astrazeneca Ab | Composto ou sal farmaceuticamente aceitável, ou um éster hidrolizável in vivo deste, pró-droga, método para a produção de um efeito antibacteriano em um animal de sangue quente, uso de um composto ou sal farmaceuticamente aceitável, ou um éster hidrolizável in vivo deste, composição farmacêutica, e, processo para a preparação de um composto ou sais farmaceuticamente aceitável, ou ésteres hidrolizáveis in vivo deste |
| US7473699B2 (en) | 2002-02-28 | 2009-01-06 | Astrazeneca Ab | 3-cyclyl-5-(nitrogen-containing 5-membered ring)methyl-oxazolidinone derivatives and their use as antibacterial agents |
| RU2004129278A (ru) | 2002-02-28 | 2005-06-10 | Астразенека Аб (Se) | Химические соединения |
| AR043050A1 (es) | 2002-09-26 | 2005-07-13 | Rib X Pharmaceuticals Inc | Compuestos heterociclicos bifuncionales y metodos para preparar y usar los mismos |
| GB0227701D0 (en) * | 2002-11-28 | 2003-01-08 | Astrazeneca Ab | Chemical compounds |
| JP2006515601A (ja) | 2002-11-28 | 2006-06-01 | アストラゼネカ アクチボラグ | 抗細菌性薬剤としてのオキサゾリジノン |
| TW200500360A (en) * | 2003-03-01 | 2005-01-01 | Astrazeneca Ab | Hydroxymethyl compounds |
| WO2005012271A2 (en) * | 2003-07-29 | 2005-02-10 | Rib-X Pharmaceuticals, Inc. | Process for the synthesis of biaryl oxazolidinones |
| US8324398B2 (en) | 2003-06-03 | 2012-12-04 | Rib-X Pharmaceuticals, Inc. | Process for the synthesis of biaryl oxazolidinones |
| MXPA05013132A (es) | 2003-06-03 | 2006-05-25 | Rib X Pharmaceuticals Inc | Compuestos heterociclicos de biarilo y metodos de produccion y su uso. |
| ES2536001T3 (es) * | 2003-07-29 | 2015-05-19 | Melinta Therapeutics, Inc. | Procedimiento para la síntesis de biariloxazolidinonas |
| US7129259B2 (en) | 2003-12-17 | 2006-10-31 | Rib-X Pharmaceuticals, Inc. | Halogenated biaryl heterocyclic compounds and methods of making and using the same |
| KR100854211B1 (ko) | 2003-12-18 | 2008-08-26 | 동아제약주식회사 | 신규한 옥사졸리디논 유도체, 그의 제조방법 및 이를유효성분으로 하는 항생제용 약학 조성물 |
| JP5383037B2 (ja) | 2004-02-27 | 2014-01-08 | リブ−エックス ファーマシューティカルズ，インコーポレイテッド | 大環状化合物およびそれらを製造し使用する方法 |
| US20080064689A1 (en) * | 2004-05-25 | 2008-03-13 | Astrazeneca Ab | 3-[4-(6-Pyridin-3-Yl)-3-Phenyl] -5-(1H-1,2,3-Triazol-1-Ylmethyl)-1,3-Oxazolidin-2-Ones as Antibacterial Agents |
| JP2008500319A (ja) * | 2004-05-25 | 2008-01-10 | アストラゼネカ アクチボラグ | 細菌感染症の治療のためのｍａｏ阻害剤としての３−（４−（２−ジヒドロイソオキサゾール−３−イルピリジン−５−イル）フェニル−５−トリアゾール−１−イルメチルオキサゾリジン−２−オン誘導体 |
| US8399660B2 (en) | 2005-06-08 | 2013-03-19 | Rib-X Pharmaceuticals, Inc. | Process for the synthesis of triazoles |
| EP2346858B1 (en) * | 2008-10-10 | 2019-08-07 | Merck Sharp & Dohme Corp. | Methods for preparing oxazolidinones and compositions containing them |
| UA114068C2 (xx) | 2009-02-03 | 2017-04-25 | Кристалічні частинки (r)-3-(4-(2-(2-метилтетразол-5-іл)піридин-5-іл)-3-фторфеніл)-5-гідроксиметилоксазолідин-2-ондиводеньфосфату | |
| US8580767B2 (en) * | 2009-05-28 | 2013-11-12 | Trius Therapeutics, Inc. | Oxazolidinone containing dimer compounds, compositions and methods to make and use |
| CN104093730A (zh) * | 2011-12-19 | 2014-10-08 | 沙特基础工业公司 | 用于制备茂金属络合物的方法 |
| CN104080792A (zh) * | 2011-12-19 | 2014-10-01 | 沙特基础工业公司 | 用于制备茂金属络合物的方法 |
| WO2021000297A1 (en) | 2019-07-03 | 2021-01-07 | Merck Sharp & Dohme Corp. | Compounds and methods of use thereof as antibacterial agents |
| CN113149924B (zh) * | 2021-03-29 | 2023-11-03 | 苏州大学 | 一种异噁唑啉的简单制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4948801A (en) * | 1988-07-29 | 1990-08-14 | E. I. Du Pont De Nemours And Company | Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents |
| DE4425613A1 (de) * | 1994-07-20 | 1996-01-25 | Bayer Ag | 5-gliedrige Heteroaryl-oxazolidinone |
| US6689779B2 (en) * | 2000-06-05 | 2004-02-10 | Dong A Pharm. Co., Ltd. | Oxazolidinone derivatives and a process for the preparation thereof |
| BR0212458A (pt) * | 2001-09-11 | 2004-10-19 | Astrazeneca Ab | Composto ou sal farmaceuticamente aceitável, ou um éster hidrolizável in vivo deste, pró-droga, método para a produção de um efeito antibacteriano em um animal de sangue quente, uso de um composto ou sal farmaceuticamente aceitável, ou um éster hidrolizável in vivo deste, composição farmacêutica, e, processo para a preparação de um composto ou sais farmaceuticamente aceitável, ou ésteres hidrolizáveis in vivo deste |
| GB0227701D0 (en) * | 2002-11-28 | 2003-01-08 | Astrazeneca Ab | Chemical compounds |
-
2003
- 2003-11-24 CA CA002507468A patent/CA2507468A1/en not_active Abandoned
- 2003-11-24 JP JP2005510253A patent/JP2006508192A/ja active Pending
- 2003-11-24 MX MXPA05005651A patent/MXPA05005651A/es unknown
- 2003-11-24 EP EP03811807A patent/EP1567532A1/en not_active Withdrawn
- 2003-11-24 AU AU2003302404A patent/AU2003302404B2/en not_active Ceased
- 2003-11-24 KR KR1020057009644A patent/KR20050085193A/ko not_active Ceased
- 2003-11-24 NZ NZ540147A patent/NZ540147A/en unknown
- 2003-11-24 BR BR0316688-0A patent/BR0316688A/pt not_active IP Right Cessation
- 2003-11-24 WO PCT/GB2003/005087 patent/WO2004048392A1/en not_active Ceased
- 2003-11-24 HK HK05112116.9A patent/HK1079794A1/zh unknown
- 2003-11-24 US US10/536,686 patent/US20060116400A1/en not_active Abandoned
-
2004
- 2004-04-01 TW TW093109096A patent/TW200533666A/zh unknown
- 2004-04-25 SA SA04250088A patent/SA04250088A/ar unknown
-
2005
- 2005-05-23 IL IL168747A patent/IL168747A0/en unknown
- 2005-05-26 NO NO20052534A patent/NO20052534L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| SA04250088A (ar) | 2005-12-03 |
| NO20052534L (no) | 2005-08-22 |
| NZ540147A (en) | 2008-03-28 |
| AU2003302404B2 (en) | 2008-06-19 |
| IL168747A0 (en) | 2009-02-11 |
| US20060116400A1 (en) | 2006-06-01 |
| NO20052534D0 (no) | 2005-05-26 |
| KR20050085193A (ko) | 2005-08-29 |
| JP2006508192A (ja) | 2006-03-09 |
| TW200533666A (en) | 2005-10-16 |
| MXPA05005651A (es) | 2005-07-27 |
| EP1567532A1 (en) | 2005-08-31 |
| AU2003302404A1 (en) | 2004-06-18 |
| WO2004048392A1 (en) | 2004-06-10 |
| BR0316688A (pt) | 2005-10-18 |
| HK1079794A1 (zh) | 2006-04-13 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |