JP2006509035A - 抗菌剤としてのｎ−（４−（ピペラジン−１−イル）−フェニル−２−オキサゾリジノン−５−カルボキサミド誘導体および関連化合物 - Google Patents
抗菌剤としてのｎ−（４−（ピペラジン−１−イル）−フェニル−２−オキサゾリジノン−５−カルボキサミド誘導体および関連化合物 Download PDFInfo
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- JP2006509035A JP2006509035A JP2004570322A JP2004570322A JP2006509035A JP 2006509035 A JP2006509035 A JP 2006509035A JP 2004570322 A JP2004570322 A JP 2004570322A JP 2004570322 A JP2004570322 A JP 2004570322A JP 2006509035 A JP2006509035 A JP 2006509035A
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- Japan
- Prior art keywords
- methyl
- oxo
- phenyl
- oxazolidine
- oxobutanoyl
- 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.)
- Withdrawn
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- 150000001875 compounds Chemical class 0.000 title claims description 76
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 title claims description 20
- 239000003242 anti bacterial agent Substances 0.000 title abstract description 4
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- -1 CF 3 Chemical group 0.000 claims description 100
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 56
- BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 40
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 31
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- HQMLIDZJXVVKCW-REOHCLBHSA-N L-alaninamide Chemical compound C[C@H](N)C(N)=O HQMLIDZJXVVKCW-REOHCLBHSA-N 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 101000655609 Streptomyces azureus Thiostrepton Proteins 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- WPZSAUFQHYFIPG-UHFFFAOYSA-N propanethioamide Chemical compound CCC(N)=S WPZSAUFQHYFIPG-UHFFFAOYSA-N 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- MYUUAWOKYLKGDW-MHZLTWQESA-N n-[[(5s)-3-[3-fluoro-4-[4-[2-[4-[(4-methylpiperazin-1-yl)methyl]phenoxy]acetyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclopropanecarbothioamide Chemical compound C1CN(C)CCN1CC(C=C1)=CC=C1OCC(=O)N1CCN(C=2C(=CC(=CC=2)N2C(O[C@@H](CNC(=S)C3CC3)C2)=O)F)CC1 MYUUAWOKYLKGDW-MHZLTWQESA-N 0.000 claims description 6
- 208000035143 Bacterial infection Diseases 0.000 claims description 5
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- WBMLMFSXGWFKFD-VWLOTQADSA-N n-[[(5s)-3-[3-fluoro-4-[4-[2-[4-(morpholin-4-ylmethyl)phenoxy]acetyl]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)COC=2C=CC(CN3CCOCC3)=CC=2)CC1 WBMLMFSXGWFKFD-VWLOTQADSA-N 0.000 claims description 5
- LNFXJBPMUANBPX-SANMLTNESA-N n-[[(5s)-3-[3-fluoro-4-[4-[2-[4-(morpholin-4-ylmethyl)phenoxy]acetyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclopropanecarbothioamide Chemical compound FC1=CC(N2C(O[C@@H](CNC(=S)C3CC3)C2)=O)=CC=C1N(CC1)CCN1C(=O)COC(C=C1)=CC=C1CN1CCOCC1 LNFXJBPMUANBPX-SANMLTNESA-N 0.000 claims description 5
- LZCQCJVOSSWKNO-SANMLTNESA-N n-[[(5s)-3-[3-fluoro-4-[4-[2-[4-[(4-methylpiperazin-1-yl)methyl]phenoxy]acetyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Chemical compound C1CN(C)CCN1CC(C=C1)=CC=C1OCC(=O)N1CCN(C=2C(=CC(=CC=2)N2C(O[C@@H](CNC(C)=O)C2)=O)F)CC1 LZCQCJVOSSWKNO-SANMLTNESA-N 0.000 claims description 5
- XPIAGTQHYMWKBS-SANMLTNESA-N n-[[(5s)-3-[3-fluoro-4-[4-[2-[4-[(4-methylpiperazin-1-yl)methyl]phenoxy]acetyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]propanethioamide Chemical compound O=C1O[C@@H](CNC(=S)CC)CN1C(C=C1F)=CC=C1N1CCN(C(=O)COC=2C=CC(CN3CCN(C)CC3)=CC=2)CC1 XPIAGTQHYMWKBS-SANMLTNESA-N 0.000 claims description 5
- YXLKRTBILAZSAE-QHCPKHFHSA-N n-[[(5s)-3-[3-fluoro-4-[4-[4-[4-(methanesulfonamidomethyl)phenyl]-4-oxobutanoyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]propanethioamide Chemical compound O=C1O[C@@H](CNC(=S)CC)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CCC(=O)C=2C=CC(CNS(C)(=O)=O)=CC=2)CC1 YXLKRTBILAZSAE-QHCPKHFHSA-N 0.000 claims description 5
- UKSYOHZMERZZEZ-SANMLTNESA-N n-[[(5s)-3-[3-fluoro-4-[4-[4-[4-(morpholin-4-ylmethyl)phenyl]-4-oxobutanoyl]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)CCC(=O)C=2C=CC(CN3CCOCC3)=CC=2)CC1 UKSYOHZMERZZEZ-SANMLTNESA-N 0.000 claims description 5
- UCQVHNHASAJZDZ-MHZLTWQESA-N n-[[(5s)-3-[3-fluoro-4-[4-[4-[4-(morpholin-4-ylmethyl)phenyl]-4-oxobutanoyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclopropanecarbothioamide Chemical compound FC1=CC(N2C(O[C@@H](CNC(=S)C3CC3)C2)=O)=CC=C1N(CC1)CCN1C(=O)CCC(=O)C(C=C1)=CC=C1CN1CCOCC1 UCQVHNHASAJZDZ-MHZLTWQESA-N 0.000 claims description 5
- YKCPGCLKTUWJSZ-SANMLTNESA-N n-[[(5s)-3-[3-fluoro-4-[4-[4-[4-(morpholin-4-ylmethyl)phenyl]-4-oxobutanoyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]propanethioamide Chemical compound O=C1O[C@@H](CNC(=S)CC)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CCC(=O)C=2C=CC(CN3CCOCC3)=CC=2)CC1 YKCPGCLKTUWJSZ-SANMLTNESA-N 0.000 claims description 5
- JUROTQWCCOSLIB-QFIPXVFZSA-N n-[[(5s)-3-[4-[1-[4-(4-aminophenyl)-4-oxobutanoyl]-3-methylazetidin-3-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]propanamide Chemical compound O=C1O[C@@H](CNC(=O)CC)CN1C1=CC=C(C2(C)CN(C2)C(=O)CCC(=O)C=2C=CC(N)=CC=2)C=C1 JUROTQWCCOSLIB-QFIPXVFZSA-N 0.000 claims description 5
- LLNJCQAPOGHJEV-QHCPKHFHSA-N n-[[(5s)-3-[4-[4-[2-[4-[(dimethylamino)methyl]phenoxy]acetyl]piperazin-1-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Chemical compound C1=CC(CN(C)C)=CC=C1OCC(=O)N1CCN(C=2C(=CC(=CC=2)N2C(O[C@@H](CNC(C)=O)C2)=O)F)CC1 LLNJCQAPOGHJEV-QHCPKHFHSA-N 0.000 claims description 5
- YKZMTEYWMJTHAP-DEOSSOPVSA-N n-[[(5s)-3-[4-[4-[2-[4-[(dimethylamino)methyl]phenoxy]acetyl]piperazin-1-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclopropanecarbothioamide Chemical compound C1=CC(CN(C)C)=CC=C1OCC(=O)N1CCN(C=2C(=CC(=CC=2)N2C(O[C@@H](CNC(=S)C3CC3)C2)=O)F)CC1 YKZMTEYWMJTHAP-DEOSSOPVSA-N 0.000 claims description 5
- LWWMMLSORCTPQZ-QHCPKHFHSA-N n-[[(5s)-3-[4-[4-[2-[4-[(dimethylamino)methyl]phenoxy]acetyl]piperazin-1-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]propanethioamide Chemical compound O=C1O[C@@H](CNC(=S)CC)CN1C(C=C1F)=CC=C1N1CCN(C(=O)COC=2C=CC(CN(C)C)=CC=2)CC1 LWWMMLSORCTPQZ-QHCPKHFHSA-N 0.000 claims description 5
- FNRRQFKKRIPHBD-DEOSSOPVSA-N n-[[(5s)-3-[4-[4-[4-[4-[(dimethylamino)methyl]phenyl]-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Chemical compound C1=CC(CN(C)C)=CC=C1C(=O)CCC(=O)N1CCN(C=2C(=CC(=CC=2)N2C(O[C@@H](CNC(C)=O)C2)=O)F)CC1 FNRRQFKKRIPHBD-DEOSSOPVSA-N 0.000 claims description 5
- JNHSVTXMYUQYQU-VWLOTQADSA-N n-[[(5s)-3-[4-[4-[4-[4-[(dimethylamino)methyl]phenyl]-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]cyclopropanecarbothioamide Chemical compound C1=CC(CN(C)C)=CC=C1C(=O)CCC(=O)N1CCN(C=2C(=CC(=CC=2)N2C(O[C@@H](CNC(=S)C3CC3)C2)=O)F)CC1 JNHSVTXMYUQYQU-VWLOTQADSA-N 0.000 claims description 5
- BOFANPUKLOQOGD-DEOSSOPVSA-N n-[[(5s)-3-[4-[4-[4-[4-[(dimethylamino)methyl]phenyl]-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]propanethioamide Chemical compound O=C1O[C@@H](CNC(=S)CC)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CCC(=O)C=2C=CC(CN(C)C)=CC=2)CC1 BOFANPUKLOQOGD-DEOSSOPVSA-N 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- IZNSVEJRYBSFRI-MBSDFSHPSA-N (2s)-n-[4-[4-[4-[4-[(5s)-5-(acetamidomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]piperazin-1-yl]-4-oxobutanoyl]phenyl]-2-aminopropanamide Chemical compound C1=CC(NC(=O)[C@@H](N)C)=CC=C1C(=O)CCC(=O)N1CCN(C=2C(=CC(=CC=2)N2C(O[C@@H](CNC(C)=O)C2)=O)F)CC1 IZNSVEJRYBSFRI-MBSDFSHPSA-N 0.000 claims description 4
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 230000001580 bacterial effect Effects 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- LMFMQQDUGDUTNM-QFIPXVFZSA-N n-[4-[4-[4-[4-[(5s)-5-(acetamidomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]piperazin-1-yl]-4-oxobutanoyl]phenyl]-2-aminoacetamide Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CCC(=O)C=2C=CC(NC(=O)CN)=CC=2)CC1 LMFMQQDUGDUTNM-QFIPXVFZSA-N 0.000 claims description 4
- JVBTWZTZCDLVSU-QHCPKHFHSA-N n-[4-[4-[4-[4-[(5s)-5-(acetamidomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl]piperazin-1-yl]-4-oxobutyl]phenyl]-2-aminoacetamide Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CCCC=2C=CC(NC(=O)CN)=CC=2)CC1 JVBTWZTZCDLVSU-QHCPKHFHSA-N 0.000 claims description 4
- DRDRWOWCXWNSMM-VWLOTQADSA-N n-[[(5s)-3-[3-fluoro-4-[4-[2-[4-(morpholin-4-ylmethyl)phenoxy]acetyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]propanethioamide Chemical compound O=C1O[C@@H](CNC(=S)CC)CN1C(C=C1F)=CC=C1N1CCN(C(=O)COC=2C=CC(CN3CCOCC3)=CC=2)CC1 DRDRWOWCXWNSMM-VWLOTQADSA-N 0.000 claims description 4
- LRPXYZLCFLVWCV-NRFANRHFSA-N n-[[(5s)-3-[3-fluoro-4-[4-[4-(3-nitrophenyl)-4-oxobutanoyl]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)CCC(=O)C=2C=C(C=CC=2)[N+]([O-])=O)CC1 LRPXYZLCFLVWCV-NRFANRHFSA-N 0.000 claims description 4
- IBIOTJOGBQXOGD-QFIPXVFZSA-N n-[[(5s)-3-[3-fluoro-4-[4-[4-(4-hydroxyphenyl)butanoyl]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)CCCC=2C=CC(O)=CC=2)CC1 IBIOTJOGBQXOGD-QFIPXVFZSA-N 0.000 claims description 4
- BSPDFNGLXYPWNU-QHCPKHFHSA-N n-[[(5s)-3-[3-fluoro-4-[4-[4-[4-(methanesulfonamidomethyl)phenyl]-4-oxobutanoyl]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)CCC(=O)C=2C=CC(CNS(C)(=O)=O)=CC=2)CC1 BSPDFNGLXYPWNU-QHCPKHFHSA-N 0.000 claims description 4
- NBACRWVWPYRZHG-FQEVSTJZSA-N n-[[(5s)-3-[4-[1-[4-(4-aminophenyl)-4-oxobutanoyl]-3-methylazetidin-3-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Chemical compound O=C1O[C@@H](CNC(=O)C)CN1C1=CC=C(C2(C)CN(C2)C(=O)CCC(=O)C=2C=CC(N)=CC=2)C(F)=C1 NBACRWVWPYRZHG-FQEVSTJZSA-N 0.000 claims description 4
- AWNZOYYANLGPAH-IBGZPJMESA-N n-[[(5s)-3-[4-[4-[4-(2-aminophenyl)-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-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)CCC(=O)C=2C(=CC=CC=2)N)CC1 AWNZOYYANLGPAH-IBGZPJMESA-N 0.000 claims description 4
- LWFRORHNUHUMQP-NRFANRHFSA-N n-[[(5s)-3-[4-[4-[4-(4-bromophenyl)-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-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)CCC(=O)C=2C=CC(Br)=CC=2)CC1 LWFRORHNUHUMQP-NRFANRHFSA-N 0.000 claims description 4
- NHRTTWVNRSYZBJ-NRFANRHFSA-N n-[[(5s)-3-[4-[4-[4-(4-bromophenyl)-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]ethanethioamide Chemical compound O=C1O[C@@H](CNC(=S)C)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CCC(=O)C=2C=CC(Br)=CC=2)CC1 NHRTTWVNRSYZBJ-NRFANRHFSA-N 0.000 claims description 4
- XCQLTNVUMBZHFI-NRFANRHFSA-N n-[[(5s)-3-[4-[4-[4-(4-chlorophenyl)-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-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)CCC(=O)C=2C=CC(Cl)=CC=2)CC1 XCQLTNVUMBZHFI-NRFANRHFSA-N 0.000 claims description 4
- MSCCKGDPBQWTEQ-NRFANRHFSA-N n-[[(5s)-3-[4-[4-[4-(4-chlorophenyl)-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]ethanethioamide Chemical compound O=C1O[C@@H](CNC(=S)C)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CCC(=O)C=2C=CC(Cl)=CC=2)CC1 MSCCKGDPBQWTEQ-NRFANRHFSA-N 0.000 claims description 4
- HGXFLNGRYDZPJJ-QFIPXVFZSA-N n-[[(5s)-3-[4-[4-[4-(4-cyanophenyl)-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-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)CCC(=O)C=2C=CC(=CC=2)C#N)CC1 HGXFLNGRYDZPJJ-QFIPXVFZSA-N 0.000 claims description 4
- ITNPKPBWRBZZSE-DEOSSOPVSA-N n-[[(5s)-3-[4-[4-[4-[4-(acetamidomethyl)phenyl]-4-oxobutanoyl]piperazin-1-yl]-3-fluorophenyl]-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)CCC(=O)C=2C=CC(CNC(C)=O)=CC=2)CC1 ITNPKPBWRBZZSE-DEOSSOPVSA-N 0.000 claims description 4
- AENPQDQJHLQZRM-DEOSSOPVSA-N n-[[4-[4-[4-[2-fluoro-4-[(5s)-2-oxo-5-[(propanethioylamino)methyl]-1,3-oxazolidin-3-yl]phenyl]piperazin-1-yl]-4-oxobutanoyl]phenyl]methyl]acetamide Chemical compound O=C1O[C@@H](CNC(=S)CC)CN1C(C=C1F)=CC=C1N1CCN(C(=O)CCC(=O)C=2C=CC(CNC(C)=O)=CC=2)CC1 AENPQDQJHLQZRM-DEOSSOPVSA-N 0.000 claims description 4
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- KPXNZSDMWKBZRB-QHCPKHFHSA-N n-[[(5s)-3-[3-fluoro-4-[4-[4-(4-methoxyphenyl)butanoyl]piperazin-1-yl]phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl]acetamide Chemical compound C1=CC(OC)=CC=C1CCCC(=O)N1CCN(C=2C(=CC(=CC=2)N2C(O[C@@H](CNC(C)=O)C2)=O)F)CC1 KPXNZSDMWKBZRB-QHCPKHFHSA-N 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- IIPJWNFOLPDTEQ-UHFFFAOYSA-N cyclopropanecarbothioamide Chemical compound NC(=S)C1CC1 IIPJWNFOLPDTEQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 284
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 161
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 156
- 239000000203 mixture Substances 0.000 description 150
- 239000007787 solid Substances 0.000 description 142
- 239000003480 eluent Substances 0.000 description 131
- 239000012258 stirred mixture Substances 0.000 description 116
- 239000000243 solution Substances 0.000 description 113
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- 239000008187 granular material Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 238000010438 heat treatment Methods 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
- 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
- 239000005457 ice water Substances 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229960003646 lysine Drugs 0.000 description 1
- 229910001623 magnesium bromide Inorganic materials 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
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- MOOYVEVEDVVKGD-UHFFFAOYSA-N oxaldehydic acid;hydrate Chemical compound O.OC(=O)C=O MOOYVEVEDVVKGD-UHFFFAOYSA-N 0.000 description 1
- 125000005880 oxathiolanyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 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
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-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 compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 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
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 229910052708 sodium Inorganic materials 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
- 238000007655 standard test method Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet 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
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 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
- 238000005636 thioacylation reaction Methods 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000006276 transfer reaction Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical group 0.000 description 1
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
-
- 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
- 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
- C07D413/12—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 chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US42802502P | 2002-11-21 | 2002-11-21 | |
| US44553003P | 2003-02-06 | 2003-02-06 | |
| PCT/IB2003/005355 WO2004045616A1 (en) | 2002-11-21 | 2003-11-19 | N-(4-(piperazin-1-yl)-phenyl-2-oxazolidinone-5-carboxamide derivates and related compounds as antibacterial agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2006509035A true JP2006509035A (ja) | 2006-03-16 |
| JP2006509035A5 JP2006509035A5 (https=) | 2006-11-30 |
Family
ID=32329201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2004570322A Withdrawn JP2006509035A (ja) | 2002-11-21 | 2003-11-19 | 抗菌剤としてのｎ−（４−（ピペラジン−１−イル）−フェニル−２−オキサゾリジノン−５−カルボキサミド誘導体および関連化合物 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US7141570B2 (https=) |
| EP (1) | EP1565186B1 (https=) |
| JP (1) | JP2006509035A (https=) |
| AR (1) | AR042086A1 (https=) |
| AT (1) | ATE344036T1 (https=) |
| AU (1) | AU2003280143A1 (https=) |
| BR (1) | BR0316483A (https=) |
| CA (1) | CA2502017A1 (https=) |
| DE (1) | DE60309504T2 (https=) |
| ES (1) | ES2271660T3 (https=) |
| MX (1) | MXPA05005472A (https=) |
| TW (1) | TW200413360A (https=) |
| WO (1) | WO2004045616A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012509313A (ja) * | 2008-11-20 | 2012-04-19 | パナセア バイオテック リミテッド | 新規な抗微生物薬 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009001192A2 (en) * | 2007-06-22 | 2008-12-31 | Orchid Research Laboratories Limited | Novel compounds and their use |
| GEP20135844B (en) | 2008-03-05 | 2013-06-10 | Takeda Pharmaceutical | Heterocyclic compound |
| WO2013189646A1 (de) | 2012-06-22 | 2013-12-27 | Henkel Ag & Co. Kgaa | Photolabile duftspeicherstoffe |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US4705799A (en) * | 1983-06-07 | 1987-11-10 | E. I. Du Pont De Nemours And Company | Aminomethyl oxooxazolidinyl benzenes useful as antibacterial agents |
| US5043443A (en) * | 1988-07-29 | 1991-08-27 | Du Pont Merck Pharmaceutical Company | Aminomethyloxooxazolidinyl arylbenzene derivatives |
| US5164510A (en) * | 1988-09-15 | 1992-11-17 | The Upjohn Company | 5'Indolinyl-5β-amidomethyloxazolidin-2-ones |
| US5225565A (en) * | 1988-09-15 | 1993-07-06 | The Upjohn Company | Antibacterial 3-(fused-ring substituted)phenyl-5β-amidomethyloxazolidin-2-ones |
| US5182403A (en) * | 1988-09-15 | 1993-01-26 | The Upjohn Company | Substituted 3(5'indazolyl) oxazolidin-2-ones |
| US5231188A (en) * | 1989-11-17 | 1993-07-27 | The Upjohn Company | Tricyclic [6.5.51]-fused oxazolidinone antibacterial agents |
| ATE146783T1 (de) * | 1991-11-01 | 1997-01-15 | Upjohn Co | Substituierte aryl- und heteroaryl- phenyloxazolidinone |
| SK283420B6 (sk) * | 1992-05-08 | 2003-07-01 | Pharmacia & Upjohn Company | Antimikrobiálne oxazolidinóny obsahujúce substituované diazínové skupiny |
| KR950702417A (ko) | 1992-07-08 | 1995-07-29 | 로렌스 티. 웰츠 | 마이코박테륨 투베르쿨로시스에 대해 유용한 5′-인돌리닐 옥사졸리디논(5′-indolinyl oxazolidinones useful against mycobacterium tuberculosis) |
| EP0673370B1 (en) * | 1992-12-08 | 1998-01-07 | PHARMACIA & UPJOHN COMPANY | Tropone-substituted phenyloxazolidinone antibacterial agents |
| MY115155A (en) | 1993-09-09 | 2003-04-30 | Upjohn Co | Substituted oxazine and thiazine oxazolidinone antimicrobials. |
| US5688792A (en) * | 1994-08-16 | 1997-11-18 | Pharmacia & Upjohn Company | Substituted oxazine and thiazine oxazolidinone antimicrobials |
| EP0730591B1 (en) | 1993-11-22 | 1999-07-14 | PHARMACIA & UPJOHN COMPANY | Esters of substituted-hydroxyacetyl piperazine phenyl oxazolidinones |
| JPH0873455A (ja) | 1994-03-15 | 1996-03-19 | Upjohn Co:The | オキサゾリジノン誘導体及びこれを有効成分とする医薬組成物 |
| DE4425609A1 (de) * | 1994-07-20 | 1996-01-25 | Bayer Ag | Benzofuranyl- und Benzothienyloxazolidinone |
| 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 |
| DE19514313A1 (de) * | 1994-08-03 | 1996-02-08 | Bayer Ag | Benzoxazolyl- und Benzothiazolyloxazolidinone |
| JP3933198B2 (ja) | 1994-10-26 | 2007-06-20 | ファルマシア・アンド・アップジョン・カンパニー | フェニルオキサゾリジノン抗菌剤 |
| BR9509673A (pt) * | 1994-11-15 | 1997-09-30 | Upjohn Co | Compostos e uso dos mesmos |
| DK0807112T3 (da) | 1995-02-03 | 2001-12-17 | Upjohn Co | Antimikrobiel heteroaromatisk ringsubstitueret phenyloxazolidinon |
| HRP960159A2 (en) * | 1995-04-21 | 1997-08-31 | Bayer Ag | Benzocyclopentane oxazolidinones containing heteroatoms |
| NZ306310A (en) | 1995-05-11 | 2001-05-25 | Upjohn Co | Spirocyclic and bicyclic diazinyl and carbazinyl oxazolidinones |
| RU2175324C2 (ru) * | 1995-09-01 | 2001-10-27 | Фармация Энд Апджон Компани | Фенилоксазолидиноны, имеющие с-с-связь с 4-8-членными гетероциклическими кольцами |
| AU6902096A (en) | 1995-09-15 | 1997-04-01 | Pharmacia & Upjohn Company | 5-amidomethyl alpha, beta-saturated and -unsaturated 3-aryl butyrolactone antibacterial agents |
| PT1019385E (pt) * | 1995-09-15 | 2004-06-30 | Upjohn Co | N-oxidos de aminoaril-oxazolidinona |
| ZA968661B (en) | 1995-11-17 | 1998-04-14 | Upjohn Co | Oxazolidinone antibacterial agent with tricyclic substituents. |
| ZA969622B (en) | 1995-12-13 | 1998-05-15 | Upjohn Co | Oxazolidinone antibacterial agents having a six-membered heteroaromatic ring. |
| DE19601265A1 (de) * | 1996-01-16 | 1997-07-17 | Bayer Ag | 2-Oxo- und 2-Thio-1,2-dihydrochinolinyl-oxazolidinone |
| DE19601264A1 (de) * | 1996-01-16 | 1997-07-17 | Bayer Ag | Pyrido-annellierte Thienyl- und Furanyl-Oxazolidinone |
| DE19601627A1 (de) * | 1996-01-18 | 1997-07-24 | Bayer Ag | Heteroatomhaltige Cyclopentanopyridyl-Oxazolidinone |
| GB9601666D0 (en) * | 1996-01-27 | 1996-03-27 | Zeneca Ltd | Chemical compounds |
| DE19604223A1 (de) * | 1996-02-06 | 1997-08-07 | Bayer Ag | Neue substituierte Oxazolidinone |
| GB9702213D0 (en) * | 1996-02-24 | 1997-03-26 | Zeneca Ltd | Chemical compounds |
| MY116093A (en) | 1996-02-26 | 2003-11-28 | Upjohn Co | Azolyl piperazinyl phenyl oxazolidinone antimicrobials |
| GB9609919D0 (en) * | 1996-05-11 | 1996-07-17 | Zeneca Ltd | Chemical compounds |
| CN1138765C (zh) | 1997-05-30 | 2004-02-18 | 法玛西雅厄普约翰美国公司 | 带有硫代羰基功能基的噁唑烷酮抗菌剂 |
| US6255304B1 (en) * | 1997-05-30 | 2001-07-03 | Pharmacia & Upjohn Company | Oxazolidinone antibacterial agents having a thiocarbonyl functionality |
| DE19730847A1 (de) | 1997-07-18 | 1999-01-28 | Bayer Ag | Tricyclisch substituierte Oxazolidinone |
| GB9717804D0 (en) * | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
| US6083967A (en) | 1997-12-05 | 2000-07-04 | Pharmacia & Upjohn Company | S-oxide and S,S-dioxide tetrahydrothiopyran phenyloxazolidinones |
| DE19802239A1 (de) | 1998-01-22 | 1999-07-29 | Bayer Ag | Neue mit Bicyclen substituierte Oxazolidinone |
| DE19802235A1 (de) | 1998-01-22 | 1999-07-29 | Bayer Ag | Mit tricyclischen Indolen substituierte Oxazolidinone |
| KR20010015910A (ko) * | 1998-01-23 | 2001-02-26 | 로렌스 티. 마이젠헬더 | 옥사졸리디논 조합 라이브러리, 조성물 및 제조 방법 |
| DE19805117A1 (de) | 1998-02-09 | 1999-08-12 | Bayer Ag | Neue Oxazolidinone mit azolhaltigen Tricyclen |
| GB9821938D0 (en) | 1998-10-09 | 1998-12-02 | Zeneca Ltd | Chemical compounds |
| JP2000204084A (ja) | 1998-11-11 | 2000-07-25 | Hokuriku Seiyaku Co Ltd | チオカルバミド酸誘導体 |
| GB9928499D0 (en) | 1999-12-03 | 2000-02-02 | Zeneca Ltd | Chemical processes and intermediates |
| GB9928568D0 (en) | 1999-12-03 | 2000-02-02 | Zeneca Ltd | Chemical compounds |
| PE20010851A1 (es) | 1999-12-14 | 2001-08-17 | Upjohn Co | Esteres del acido benzoico de oxazolidinonas que tienen un substituyente hidroxiacetilpiperazina |
| US6642238B2 (en) * | 2000-02-10 | 2003-11-04 | Pharmacia And Upjohn Company | Oxazolidinone thioamides with piperazine amide substituents |
| JP2003522763A (ja) * | 2000-02-10 | 2003-07-29 | ファルマシア・アンド・アップジョン・カンパニー | ピペラジンアミド置換基を持つオキサゾリジノンチオアミド |
| GB0009803D0 (en) | 2000-04-25 | 2000-06-07 | Astrazeneca Ab | Chemical compounds |
| DE60118241T2 (de) * | 2000-10-17 | 2006-12-28 | Pharmacia & Upjohn Co. Llc, Kalamazoo | Verfahren zur herstellung von oxazolidinonverbindungen |
| EP1409464A4 (en) | 2001-07-16 | 2005-11-02 | Ranbaxy Lab Ltd | OXAZOLIDINONE DERIVATIVES AS POTENTIAL ANTIMICROBIALS |
-
2003
- 2003-11-19 JP JP2004570322A patent/JP2006509035A/ja not_active Withdrawn
- 2003-11-19 WO PCT/IB2003/005355 patent/WO2004045616A1/en not_active Ceased
- 2003-11-19 DE DE60309504T patent/DE60309504T2/de not_active Expired - Fee Related
- 2003-11-19 EP EP03772516A patent/EP1565186B1/en not_active Expired - Lifetime
- 2003-11-19 CA CA002502017A patent/CA2502017A1/en not_active Abandoned
- 2003-11-19 AR ARP030104276A patent/AR042086A1/es unknown
- 2003-11-19 ES ES03772516T patent/ES2271660T3/es not_active Expired - Lifetime
- 2003-11-19 MX MXPA05005472A patent/MXPA05005472A/es active IP Right Grant
- 2003-11-19 AU AU2003280143A patent/AU2003280143A1/en not_active Abandoned
- 2003-11-19 AT AT03772516T patent/ATE344036T1/de not_active IP Right Cessation
- 2003-11-19 US US10/717,237 patent/US7141570B2/en not_active Expired - Fee Related
- 2003-11-19 BR BR0316483-7A patent/BR0316483A/pt not_active IP Right Cessation
- 2003-11-20 TW TW092132583A patent/TW200413360A/zh unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012509313A (ja) * | 2008-11-20 | 2012-04-19 | パナセア バイオテック リミテッド | 新規な抗微生物薬 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2502017A1 (en) | 2004-06-03 |
| US7141570B2 (en) | 2006-11-28 |
| DE60309504D1 (de) | 2006-12-14 |
| MXPA05005472A (es) | 2005-07-25 |
| ES2271660T3 (es) | 2007-04-16 |
| BR0316483A (pt) | 2005-10-11 |
| EP1565186A1 (en) | 2005-08-24 |
| US20040142939A1 (en) | 2004-07-22 |
| EP1565186B1 (en) | 2006-11-02 |
| DE60309504T2 (de) | 2007-05-16 |
| AU2003280143A1 (en) | 2004-06-15 |
| AR042086A1 (es) | 2005-06-08 |
| TW200413360A (en) | 2004-08-01 |
| WO2004045616A1 (en) | 2004-06-03 |
| ATE344036T1 (de) | 2006-11-15 |
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