SG193367A1 - Isoxazole derivatives useful as antibacterial agents - Google Patents

Info

Publication number

SG193367A1

SG193367A1 SG2013067616A SG2013067616A SG193367A1 SG 193367 A1 SG193367 A1 SG 193367A1 SG 2013067616 A SG2013067616 A SG 2013067616A SG 2013067616 A SG2013067616 A SG 2013067616A SG 193367 A1 SG193367 A1 SG 193367A1

Authority

SG

Singapore

Prior art keywords

methyl

methylsulfonyl

hydroxy

alkyl

isoxazol

Prior art date

2011-04-08

Links

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• 239000003242 anti bacterial agent Substances 0.000 title description 5
• 150000002545 isoxazoles Chemical class 0.000 title description 2
• 208000035143 Bacterial infection Diseases 0.000 claims abstract description 9
• 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 9
• 125000000217 alkyl group Chemical group 0.000 claims description 167
• -1 methylenedioxy Chemical group 0.000 claims description 124
• 150000001875 compounds Chemical class 0.000 claims description 117
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
• 125000003545 alkoxy group Chemical group 0.000 claims description 43
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 35
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
• 238000000034 method Methods 0.000 claims description 31
• 125000000623 heterocyclic group Chemical group 0.000 claims description 26
• 150000003839 salts Chemical class 0.000 claims description 26
• 125000001072 heteroaryl group Chemical group 0.000 claims description 24
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 21
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 21
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 19
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 19
• 125000003118 aryl group Chemical group 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 17
• 125000004414 alkyl thio group Chemical group 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
• 125000001424 substituent group Chemical group 0.000 claims description 13
• 125000004104 aryloxy group Chemical group 0.000 claims description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
• 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 8
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 8
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 7
• 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 6
• 230000000694 effects Effects 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 125000005368 heteroarylthio group Chemical group 0.000 claims description 5
• 125000002757 morpholinyl group Chemical group 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
• 125000001544 thienyl group Chemical group 0.000 claims description 5
• NXOTUZBMBWOEIM-MRXNPFEDSA-N (2r)-4-[3-(2-fluoro-3-methoxyphenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical group COC1=CC=CC(C2=NOC(CC[C@](C)(C(=O)NO)S(C)(=O)=O)=C2)=C1F NXOTUZBMBWOEIM-MRXNPFEDSA-N 0.000 claims description 4
• 125000005110 aryl thio group Chemical group 0.000 claims description 4
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
• 125000005366 cycloalkylthio group Chemical group 0.000 claims description 4
• 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• HCERQTLDRDZHNO-MRXNPFEDSA-N (2r)-4-[5-(2-fluoro-3-methoxyphenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound COC1=CC=CC(C=2ON=C(CC[C@](C)(C(=O)NO)S(C)(=O)=O)C=2)=C1F HCERQTLDRDZHNO-MRXNPFEDSA-N 0.000 claims description 3
• 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 3
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• QQNMJEMOLKXMFB-UHFFFAOYSA-N 4-[3-(5-ethylthiophen-2-yl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical group S1C(CC)=CC=C1C1=NOC(CCC(C)(C(=O)NO)S(C)(=O)=O)=C1 QQNMJEMOLKXMFB-UHFFFAOYSA-N 0.000 claims description 2
• SIUYFAFARGZKKQ-UHFFFAOYSA-N 4-[5-(2-fluorophenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1N=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=C1C1=CC=CC=C1F SIUYFAFARGZKKQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 2
• 125000001188 haloalkyl group Chemical group 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
• 125000001475 halogen functional group Chemical group 0.000 claims 2
• DJLDAJVHUGRNKZ-MRXNPFEDSA-N (2r)-4-[3-(2-fluoro-4-methoxyphenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound FC1=CC(OC)=CC=C1C1=NOC(CC[C@](C)(C(=O)NO)S(C)(=O)=O)=C1 DJLDAJVHUGRNKZ-MRXNPFEDSA-N 0.000 claims 1
• JAZICKKQBWPPLG-MRXNPFEDSA-N (2r)-4-[5-(2-fluoro-4-methoxyphenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound FC1=CC(OC)=CC=C1C1=CC(CC[C@](C)(C(=O)NO)S(C)(=O)=O)=NO1 JAZICKKQBWPPLG-MRXNPFEDSA-N 0.000 claims 1
• UFVGRHULTNFZNW-UHFFFAOYSA-N 4-[3-(1,3-benzodioxol-5-yl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1C(CCC(C)(C(=O)NO)S(C)(=O)=O)=CC(C=2C=C3OCOC3=CC=2)=N1 UFVGRHULTNFZNW-UHFFFAOYSA-N 0.000 claims 1
• FHSUWVXCKYWKQC-UHFFFAOYSA-N 4-[3-(2,4-difluorophenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1C(CCC(C)(C(=O)NO)S(C)(=O)=O)=CC(C=2C(=CC(F)=CC=2)F)=N1 FHSUWVXCKYWKQC-UHFFFAOYSA-N 0.000 claims 1
• HGHOSHSDKFHZHE-UHFFFAOYSA-N 4-[3-(2,6-dimethoxyphenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound COC1=CC=CC(OC)=C1C1=NOC(CCC(C)(C(=O)NO)S(C)(=O)=O)=C1 HGHOSHSDKFHZHE-UHFFFAOYSA-N 0.000 claims 1
• PBABRFLCYVRPGQ-UHFFFAOYSA-N 4-[3-(2-ethoxypropan-2-yl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound CCOC(C)(C)C=1C=C(CCC(C)(C(=O)NO)S(C)(=O)=O)ON=1 PBABRFLCYVRPGQ-UHFFFAOYSA-N 0.000 claims 1
• VXTCDBXHICHZMI-UHFFFAOYSA-N 4-[3-(3,4-difluorophenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1C(CCC(C)(C(=O)NO)S(C)(=O)=O)=CC(C=2C=C(F)C(F)=CC=2)=N1 VXTCDBXHICHZMI-UHFFFAOYSA-N 0.000 claims 1
• WURMAIUGSVDXNQ-UHFFFAOYSA-N 4-[3-(3,4-dimethoxyphenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound C1=C(OC)C(OC)=CC=C1C1=NOC(CCC(C)(C(=O)NO)S(C)(=O)=O)=C1 WURMAIUGSVDXNQ-UHFFFAOYSA-N 0.000 claims 1
• BLYGFQFTPVQVEJ-UHFFFAOYSA-N 4-[3-(3-fluoro-4-morpholin-4-ylphenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1C(CCC(C)(C(=O)NO)S(C)(=O)=O)=CC(C=2C=C(F)C(N3CCOCC3)=CC=2)=N1 BLYGFQFTPVQVEJ-UHFFFAOYSA-N 0.000 claims 1
• PYDSRUSDMQVQJD-UHFFFAOYSA-N 4-[3-(3-fluorophenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1C(CCC(C)(C(=O)NO)S(C)(=O)=O)=CC(C=2C=C(F)C=CC=2)=N1 PYDSRUSDMQVQJD-UHFFFAOYSA-N 0.000 claims 1
• FQLMYDRKOBWRFB-UHFFFAOYSA-N 4-[3-(3-fluoropyridin-2-yl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1C(CCC(C)(C(=O)NO)S(C)(=O)=O)=CC(C=2C(=CC=CN=2)F)=N1 FQLMYDRKOBWRFB-UHFFFAOYSA-N 0.000 claims 1
• VNMAFOGPKMKWCF-UHFFFAOYSA-N 4-[3-(3-fluoropyridin-4-yl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1C(CCC(C)(C(=O)NO)S(C)(=O)=O)=CC(C=2C(=CN=CC=2)F)=N1 VNMAFOGPKMKWCF-UHFFFAOYSA-N 0.000 claims 1
• UOSUVHHPJJREPU-UHFFFAOYSA-N 4-[3-(4-fluorophenyl)-1,2-oxazol-5-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1C(CCC(C)(C(=O)NO)S(C)(=O)=O)=CC(C=2C=CC(F)=CC=2)=N1 UOSUVHHPJJREPU-UHFFFAOYSA-N 0.000 claims 1
• CVXUCGSXHDPRDD-UHFFFAOYSA-N 4-[5-(2,3-dichlorophenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1N=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=C1C1=CC=CC(Cl)=C1Cl CVXUCGSXHDPRDD-UHFFFAOYSA-N 0.000 claims 1
• IWMSWYUSDRQELY-UHFFFAOYSA-N 4-[5-(2,4-difluorophenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1N=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=C1C1=CC=C(F)C=C1F IWMSWYUSDRQELY-UHFFFAOYSA-N 0.000 claims 1
• VRUGEGDNLIATDC-UHFFFAOYSA-N 4-[5-(2,6-dichlorophenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1N=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=C1C1=C(Cl)C=CC=C1Cl VRUGEGDNLIATDC-UHFFFAOYSA-N 0.000 claims 1
• RCPSDMXTLOQNBB-UHFFFAOYSA-N 4-[5-(2,6-dimethoxyphenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound COC1=CC=CC(OC)=C1C1=CC(CCC(C)(C(=O)NO)S(C)(=O)=O)=NO1 RCPSDMXTLOQNBB-UHFFFAOYSA-N 0.000 claims 1
• XEZBUYBPJBBXKU-UHFFFAOYSA-N 4-[5-(3,4-dichlorophenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1N=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=C1C1=CC=C(Cl)C(Cl)=C1 XEZBUYBPJBBXKU-UHFFFAOYSA-N 0.000 claims 1
• HCAKSFLTMKRPJR-UHFFFAOYSA-N 4-[5-(3-fluorophenyl)-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1N=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=C1C1=CC=CC(F)=C1 HCAKSFLTMKRPJR-UHFFFAOYSA-N 0.000 claims 1
• LUDYQCRRUQMFRZ-UHFFFAOYSA-N 4-[5-[[cyclopropyl(2-phenoxyethyl)amino]methyl]-1,2-oxazol-3-yl]-n-hydroxy-2-methyl-2-methylsulfonylbutanamide Chemical compound O1N=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=C1CN(C1CC1)CCOC1=CC=CC=C1 LUDYQCRRUQMFRZ-UHFFFAOYSA-N 0.000 claims 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
• OMCCRZYPUNCTEJ-UHFFFAOYSA-N n-hydroxy-2-methyl-4-[3-(4-methylphenyl)-1,2-oxazol-5-yl]-2-methylsulfonylbutanamide Chemical compound C1=CC(C)=CC=C1C1=NOC(CCC(C)(C(=O)NO)S(C)(=O)=O)=C1 OMCCRZYPUNCTEJ-UHFFFAOYSA-N 0.000 claims 1
• BAVRGNFFDYFLLR-UHFFFAOYSA-N n-hydroxy-2-methyl-4-[5-(3-methylphenyl)-1,2-oxazol-3-yl]-2-methylsulfonylbutanamide Chemical compound CC1=CC=CC(C=2ON=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=2)=C1 BAVRGNFFDYFLLR-UHFFFAOYSA-N 0.000 claims 1
• XGIRSBWWENVALN-UHFFFAOYSA-N n-hydroxy-4-[3-(2-methoxyphenyl)-1,2-oxazol-5-yl]-2-methyl-2-methylsulfonylbutanamide Chemical compound COC1=CC=CC=C1C1=NOC(CCC(C)(C(=O)NO)S(C)(=O)=O)=C1 XGIRSBWWENVALN-UHFFFAOYSA-N 0.000 claims 1
• LEPPADCKLYASMI-UHFFFAOYSA-N n-hydroxy-4-[3-(4-methoxyphenyl)-1,2-oxazol-5-yl]-2-methyl-2-methylsulfonylbutanamide Chemical compound C1=CC(OC)=CC=C1C1=NOC(CCC(C)(C(=O)NO)S(C)(=O)=O)=C1 LEPPADCKLYASMI-UHFFFAOYSA-N 0.000 claims 1
• BSCJVTMTVNHJBP-UHFFFAOYSA-N n-hydroxy-4-[5-(2-methoxyphenyl)-1,2-oxazol-3-yl]-2-methyl-2-methylsulfonylbutanamide Chemical compound COC1=CC=CC=C1C1=CC(CCC(C)(C(=O)NO)S(C)(=O)=O)=NO1 BSCJVTMTVNHJBP-UHFFFAOYSA-N 0.000 claims 1
• FKPQSKNQNUTQIJ-UHFFFAOYSA-N n-hydroxy-4-[5-(3-methoxyphenyl)-1,2-oxazol-3-yl]-2-methyl-2-methylsulfonylbutanamide Chemical compound COC1=CC=CC(C=2ON=C(CCC(C)(C(=O)NO)S(C)(=O)=O)C=2)=C1 FKPQSKNQNUTQIJ-UHFFFAOYSA-N 0.000 claims 1
• WDMWLDLIXNEGSQ-UHFFFAOYSA-N n-hydroxy-4-[5-(9-hydroxynonyl)-1,2-oxazol-3-yl]-2-methyl-2-methylsulfonylbutanamide Chemical compound ONC(=O)C(S(C)(=O)=O)(C)CCC=1C=C(CCCCCCCCCO)ON=1 WDMWLDLIXNEGSQ-UHFFFAOYSA-N 0.000 claims 1
• AERPGCYOXMZKJB-UHFFFAOYSA-N n-hydroxy-4-[5-[(2-methoxyphenoxy)methyl]-1,2-oxazol-3-yl]-2-methyl-2-methylsulfonylbutanamide Chemical compound COC1=CC=CC=C1OCC1=CC(CCC(C)(C(=O)NO)S(C)(=O)=O)=NO1 AERPGCYOXMZKJB-UHFFFAOYSA-N 0.000 claims 1
• HXIRTSKHPFRRKO-UHFFFAOYSA-N o-methyl carbamothioate Chemical compound COC(N)=S HXIRTSKHPFRRKO-UHFFFAOYSA-N 0.000 claims 1
• 239000002253 acid Substances 0.000 abstract description 12
• NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 abstract description 5
• 239000003112 inhibitor Substances 0.000 abstract description 4
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• 241000894006 Bacteria Species 0.000 description 19
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