ZA200202631B - Fab I inhibitors. - Google Patents
Fab I inhibitors. Download PDFInfo
- Publication number
- ZA200202631B ZA200202631B ZA200202631A ZA200202631A ZA200202631B ZA 200202631 B ZA200202631 B ZA 200202631B ZA 200202631 A ZA200202631 A ZA 200202631A ZA 200202631 A ZA200202631 A ZA 200202631A ZA 200202631 B ZA200202631 B ZA 200202631B
- Authority
- ZA
- South Africa
- Prior art keywords
- methyl
- ylmethyl
- indol
- acrylamide
- aminopyridin
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 177
- 238000000034 method Methods 0.000 claims description 45
- -1 2-hydroxyethylamino Chemical group 0.000 claims description 27
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 27
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 22
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 20
- 230000005764 inhibitory process Effects 0.000 claims description 17
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 claims description 13
- 208000035143 Bacterial infection Diseases 0.000 claims description 10
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- KFWWCMJSYSSPSK-PAXLJYGASA-N crotonoyl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)/C=C/C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 KFWWCMJSYSSPSK-PAXLJYGASA-N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 6
- 230000001580 bacterial effect Effects 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- 102000014914 Carrier Proteins Human genes 0.000 claims description 3
- 108010078791 Carrier Proteins Proteins 0.000 claims description 3
- 125000001475 halogen functional group Chemical group 0.000 claims description 3
- 239000003446 ligand Substances 0.000 claims description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 claims description 2
- 208000015181 infectious disease Diseases 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- IMWUGPHNSTULFK-BQYQJAHWSA-N (e)-3-(1h-imidazo[4,5-b]pyridin-6-yl)-n-methyl-n-[(1-methylindol-2-yl)methyl]prop-2-enamide Chemical compound N1=C2NC=NC2=CC(/C=C/C(=O)N(CC=2N(C3=CC=CC=C3C=2)C)C)=C1 IMWUGPHNSTULFK-BQYQJAHWSA-N 0.000 claims 1
- PNMPFAFBLNQANS-VOTSOKGWSA-N (e)-3-(2-aminopyrimidin-5-yl)-n-(1-benzothiophen-2-ylmethyl)-n-methylprop-2-enamide Chemical compound C=1C2=CC=CC=C2SC=1CN(C)C(=O)\C=C\C1=CN=C(N)N=C1 PNMPFAFBLNQANS-VOTSOKGWSA-N 0.000 claims 1
- FQUDHFUOBXDJFI-BQYQJAHWSA-N (e)-3-(2-aminopyrimidin-5-yl)-n-methyl-n-[(1-methylindol-3-yl)methyl]prop-2-enamide Chemical compound C=1N(C)C2=CC=CC=C2C=1CN(C)C(=O)\C=C\C1=CN=C(N)N=C1 FQUDHFUOBXDJFI-BQYQJAHWSA-N 0.000 claims 1
- PFHMCRSTFZDTOY-CXUHLZMHSA-N (e)-3-(3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazin-7-yl)-n-methyl-2-[(1-methylindol-2-yl)methyl]prop-2-enamide Chemical compound N1CCOC2=CC(/C=C(\CC=3N(C4=CC=CC=C4C=3)C)C(=O)NC)=CN=C21 PFHMCRSTFZDTOY-CXUHLZMHSA-N 0.000 claims 1
- LVJNPHOHTRAEBH-MDZDMXLPSA-N (e)-3-(6-acetamido-5-methylpyridin-3-yl)-n-methyl-n-[(1-methylindol-2-yl)methyl]prop-2-enamide Chemical compound C=1C2=CC=CC=C2N(C)C=1CN(C)C(=O)\C=C\C1=CN=C(NC(C)=O)C(C)=C1 LVJNPHOHTRAEBH-MDZDMXLPSA-N 0.000 claims 1
- SDZCXBKHEBVJTI-PKNBQFBNSA-N (e)-3-(6-acetamidopyridin-3-yl)-n-methyl-n-[(1-methylindol-2-yl)methyl]prop-2-enamide Chemical compound C=1C2=CC=CC=C2N(C)C=1CN(C)C(=O)\C=C\C1=CC=C(NC(C)=O)N=C1 SDZCXBKHEBVJTI-PKNBQFBNSA-N 0.000 claims 1
- GTDUUMXTIFTGMU-PKNBQFBNSA-N (e)-3-(6-acetamidopyridin-3-yl)-n-methyl-n-[(3-methyl-1h-inden-2-yl)methyl]prop-2-enamide Chemical compound CC=1C2=CC=CC=C2CC=1CN(C)C(=O)\C=C\C1=CC=C(NC(C)=O)N=C1 GTDUUMXTIFTGMU-PKNBQFBNSA-N 0.000 claims 1
- HBSMKEQYXMTPIW-CMDGGOBGSA-N (e)-3-(6-amino-4-methylpyridin-3-yl)-n-methyl-n-[(1-methylindol-2-yl)methyl]prop-2-enamide Chemical compound C=1C2=CC=CC=C2N(C)C=1CN(C)C(=O)\C=C\C1=CN=C(N)C=C1C HBSMKEQYXMTPIW-CMDGGOBGSA-N 0.000 claims 1
- NQYBCPJJUKCEMY-BQYQJAHWSA-N (e)-3-(6-amino-5-methylpyridin-3-yl)-n-(1-benzothiophen-2-ylmethyl)-n-methylprop-2-enamide Chemical compound C=1C2=CC=CC=C2SC=1CN(C)C(=O)\C=C\C1=CN=C(N)C(C)=C1 NQYBCPJJUKCEMY-BQYQJAHWSA-N 0.000 claims 1
- DGDIBHHWRBJFJV-CSKARUKUSA-N (e)-3-(6-amino-5-methylpyridin-3-yl)-n-methyl-n-(naphthalen-2-ylmethyl)prop-2-enamide Chemical compound C=1C=C2C=CC=CC2=CC=1CN(C)C(=O)\C=C\C1=CN=C(N)C(C)=C1 DGDIBHHWRBJFJV-CSKARUKUSA-N 0.000 claims 1
- LDQBZZLUBKWRFO-CMDGGOBGSA-N (e)-3-(6-amino-5-methylpyridin-3-yl)-n-methyl-n-[(1-methylindol-2-yl)methyl]prop-2-enamide Chemical compound C=1C2=CC=CC=C2N(C)C=1CN(C)C(=O)\C=C\C1=CN=C(N)C(C)=C1 LDQBZZLUBKWRFO-CMDGGOBGSA-N 0.000 claims 1
- ZETXDXUSCQAARQ-VQHVLOKHSA-N (e)-3-(6-aminopyridin-3-yl)-n-(1-benzofuran-2-ylmethyl)-n-methylprop-2-enamide Chemical compound C=1C2=CC=CC=C2OC=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 ZETXDXUSCQAARQ-VQHVLOKHSA-N 0.000 claims 1
- HKVKIAWIOKGVEH-VQHVLOKHSA-N (e)-3-(6-aminopyridin-3-yl)-n-(1-benzothiophen-2-ylmethyl)-n-methylprop-2-enamide Chemical compound C=1C2=CC=CC=C2SC=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 HKVKIAWIOKGVEH-VQHVLOKHSA-N 0.000 claims 1
- LYOBJGHPKSQOSR-VQHVLOKHSA-N (e)-3-(6-aminopyridin-3-yl)-n-(1-benzothiophen-3-ylmethyl)-n-methylprop-2-enamide Chemical compound C=1SC2=CC=CC=C2C=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 LYOBJGHPKSQOSR-VQHVLOKHSA-N 0.000 claims 1
- OPMOFXBJTDXTAK-PKNBQFBNSA-N (e)-3-(6-aminopyridin-3-yl)-n-[(1,3-dimethylindol-2-yl)methyl]-n-methylprop-2-enamide Chemical compound CC=1C2=CC=CC=C2N(C)C=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 OPMOFXBJTDXTAK-PKNBQFBNSA-N 0.000 claims 1
- RNXRNMOULXMEDN-PKNBQFBNSA-N (e)-3-(6-aminopyridin-3-yl)-n-[(1-ethylindol-2-yl)methyl]-n-methylprop-2-enamide Chemical compound C=1C2=CC=CC=C2N(CC)C=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 RNXRNMOULXMEDN-PKNBQFBNSA-N 0.000 claims 1
- SEOLMOHBQKKAAN-PKNBQFBNSA-N (e)-3-(6-aminopyridin-3-yl)-n-[(1-methylindol-2-yl)methyl]-n-propylprop-2-enamide Chemical compound C=1C2=CC=CC=C2N(C)C=1CN(CCC)C(=O)\C=C\C1=CC=C(N)N=C1 SEOLMOHBQKKAAN-PKNBQFBNSA-N 0.000 claims 1
- SEJYCBCZTWKYPG-XBXARRHUSA-N (e)-3-(6-aminopyridin-3-yl)-n-[(5-fluoro-1-methylindol-2-yl)methyl]-n-methylprop-2-enamide Chemical compound C=1C2=CC(F)=CC=C2N(C)C=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 SEJYCBCZTWKYPG-XBXARRHUSA-N 0.000 claims 1
- UAZHLKPARLBPQD-WEVVVXLNSA-N (e)-3-(6-aminopyridin-3-yl)-n-[(6-methoxy-1-methylindol-2-yl)methyl]-n-methylprop-2-enamide Chemical compound CN1C2=CC(OC)=CC=C2C=C1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 UAZHLKPARLBPQD-WEVVVXLNSA-N 0.000 claims 1
- VIKCFMOEGWTAAA-YRNVUSSQSA-N (e)-3-(6-aminopyridin-3-yl)-n-cyclopropyl-n-[(1-methylindol-2-yl)methyl]prop-2-enamide Chemical compound C=1C2=CC=CC=C2N(C)C=1CN(C(=O)\C=C\C=1C=NC(N)=CC=1)C1CC1 VIKCFMOEGWTAAA-YRNVUSSQSA-N 0.000 claims 1
- UBIOJRRUVLPOHF-ZRDIBKRKSA-N (e)-3-(6-aminopyridin-3-yl)-n-methyl-n-(naphthalen-1-ylmethyl)prop-2-enamide Chemical compound C=1C=CC2=CC=CC=C2C=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 UBIOJRRUVLPOHF-ZRDIBKRKSA-N 0.000 claims 1
- MYKWIYXAYVQRBX-DHZHZOJOSA-N (e)-3-(6-aminopyridin-3-yl)-n-methyl-n-(naphthalen-2-ylmethyl)prop-2-enamide Chemical compound C=1C=C2C=CC=CC2=CC=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 MYKWIYXAYVQRBX-DHZHZOJOSA-N 0.000 claims 1
- MORDWTPUPJUELD-VQHVLOKHSA-N (e)-3-(6-aminopyridin-3-yl)-n-methyl-n-(quinolin-3-ylmethyl)prop-2-enamide Chemical compound C=1N=C2C=CC=CC2=CC=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 MORDWTPUPJUELD-VQHVLOKHSA-N 0.000 claims 1
- VRXXZIHCBJCSJS-HWKANZROSA-N (e)-3-(6-aminopyridin-3-yl)-n-methyl-n-(thieno[2,3-b]thiophen-5-ylmethyl)prop-2-enamide Chemical compound C=1C=2C=CSC=2SC=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 VRXXZIHCBJCSJS-HWKANZROSA-N 0.000 claims 1
- NCRRMWXEJJVRGR-CSKARUKUSA-N (e)-3-(6-aminopyridin-3-yl)-n-methyl-n-[(1-methylindazol-3-yl)methyl]prop-2-enamide Chemical compound N=1N(C)C2=CC=CC=C2C=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 NCRRMWXEJJVRGR-CSKARUKUSA-N 0.000 claims 1
- DEGANAFKDPOYCK-GXDHUFHOSA-N (e)-3-(6-aminopyridin-3-yl)-n-methyl-n-[(1-methylindol-2-yl)methyl]but-2-enamide Chemical compound C=1C2=CC=CC=C2N(C)C=1CN(C)C(=O)\C=C(/C)C1=CC=C(N)N=C1 DEGANAFKDPOYCK-GXDHUFHOSA-N 0.000 claims 1
- AENYXTUUUAWXHS-CSKARUKUSA-N (e)-3-(6-aminopyridin-3-yl)-n-methyl-n-[(2-methyl-1h-indol-3-yl)methyl]prop-2-enamide Chemical compound CC=1NC2=CC=CC=C2C=1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 AENYXTUUUAWXHS-CSKARUKUSA-N 0.000 claims 1
- DVQXQQLRSLOIKR-CSKARUKUSA-N (e)-3-(6-aminopyridin-3-yl)-n-methyl-n-[(3-methyl-1-benzothiophen-2-yl)methyl]prop-2-enamide Chemical compound S1C2=CC=CC=C2C(C)=C1CN(C)C(=O)\C=C\C1=CC=C(N)N=C1 DVQXQQLRSLOIKR-CSKARUKUSA-N 0.000 claims 1
- NURLKLVHAJESQU-PKNBQFBNSA-N (e)-n-methyl-3-[6-(methylamino)pyridin-3-yl]-n-[(1-methylindol-2-yl)methyl]prop-2-enamide Chemical compound C1=NC(NC)=CC=C1\C=C\C(=O)N(C)CC1=CC2=CC=CC=C2N1C NURLKLVHAJESQU-PKNBQFBNSA-N 0.000 claims 1
- SUSSQZFKCNQFQS-BQYQJAHWSA-N (e)-n-methyl-n-[(1-methylindol-2-yl)methyl]-3-(2-oxo-1,4-dihydropyrido[2,3-d][1,3]oxazin-6-yl)prop-2-enamide Chemical compound N1C(=O)OCC2=CC(/C=C/C(=O)N(CC=3N(C4=CC=CC=C4C=3)C)C)=CN=C21 SUSSQZFKCNQFQS-BQYQJAHWSA-N 0.000 claims 1
- WNBHKHHXEHQTLZ-CMDGGOBGSA-N (e)-n-methyl-n-[(1-methylindol-2-yl)methyl]-3-(3-methyl-2-oxo-1,4-dihydropyrido[2,3-d]pyrimidin-6-yl)prop-2-enamide Chemical compound N1C(=O)N(C)CC2=CC(/C=C/C(=O)N(CC=3N(C4=CC=CC=C4C=3)C)C)=CN=C21 WNBHKHHXEHQTLZ-CMDGGOBGSA-N 0.000 claims 1
- YWRXDGYUFPGSDH-MDZDMXLPSA-N (e)-n-methyl-n-[(1-methylindol-2-yl)methyl]-3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)prop-2-enamide Chemical compound N1CCCC2=CC(/C=C/C(=O)N(CC=3N(C4=CC=CC=C4C=3)C)C)=CN=C21 YWRXDGYUFPGSDH-MDZDMXLPSA-N 0.000 claims 1
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- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
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- 238000010186 staining Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
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- 238000006467 substitution reaction Methods 0.000 description 1
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- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- HFYKFRBQZCCJRD-UHFFFAOYSA-N tert-butyl 3,4-dihydro-2h-1,8-naphthyridine-1-carboxylate Chemical compound C1=CN=C2N(C(=O)OC(C)(C)C)CCCC2=C1 HFYKFRBQZCCJRD-UHFFFAOYSA-N 0.000 description 1
- MAQRNFMOCRQXAB-UHFFFAOYSA-N tert-butyl 6-bromo-3,4-dihydro-2h-1,8-naphthyridine-1-carboxylate Chemical compound BrC1=CN=C2N(C(=O)OC(C)(C)C)CCCC2=C1 MAQRNFMOCRQXAB-UHFFFAOYSA-N 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- GVZXSZWCZGKLRS-UHFFFAOYSA-N thieno[3,2-b]thiophene-5-carboxylic acid Chemical compound S1C=CC2=C1C=C(C(=O)O)S2 GVZXSZWCZGKLRS-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003738 xylenes Chemical class 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/72—Nitrogen atoms
- C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61K31/5365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines ortho- or peri-condensed with heterocyclic ring systems
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/52—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring condensed with a ring other than six-membered
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Applications Claiming Priority (1)
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US15870499P | 1999-10-08 | 1999-10-08 |
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ZA200202631A ZA200202631B (en) | 1999-10-08 | 2002-04-04 | Fab I inhibitors. |
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Families Citing this family (52)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CO5180550A1 (es) | 1999-04-19 | 2002-07-30 | Smithkline Beecham Corp | Inhibidores de fab i |
CO5370679A1 (es) | 1999-06-01 | 2004-02-27 | Smithkline Beecham Corp | Inhibidores fab 1 |
EP1225894B1 (en) * | 1999-10-08 | 2006-07-05 | Affinium Pharmaceuticals, Inc. | Fab i inhibitors |
US6730684B1 (en) | 1999-10-08 | 2004-05-04 | Affinium Pharmaceuticals, Inc. | Fab I inhibitors |
US6762201B1 (en) | 1999-10-08 | 2004-07-13 | Affinium Pharmaceuticals, Inc. | Fab I inhibitors |
ES2231275T3 (es) | 1999-10-08 | 2005-05-16 | Affinium Pharmaceuticals, Inc. | Inhibidores de fab i. |
JP4272338B2 (ja) | 2000-09-22 | 2009-06-03 | バイエル アクチェンゲゼルシャフト | ピリジン誘導体 |
US7048926B2 (en) | 2000-10-06 | 2006-05-23 | Affinium Pharmaceuticals, Inc. | Methods of agonizing and antagonizing FabK |
WO2002031128A1 (en) * | 2000-10-06 | 2002-04-18 | Smithkline Beecham Corporation | Methods of agonizing and antagonizing fabk |
DE60230934D1 (de) * | 2001-04-06 | 2009-03-05 | Affinium Pharm Inc | Fab-i-inhibitoren |
ES2518316T3 (es) * | 2002-12-06 | 2014-11-05 | Debiopharm International Sa | Compuestos heterocíclicos, métodos de fabricación de los mismos y su uso en terapia |
DE602004016831D1 (de) * | 2003-03-17 | 2008-11-13 | Affinium Pharm Inc | Pharmazeutische zusammensetzungen inhibitoren von fab i und weitere antibiotika enthaltend |
KR20060128976A (ko) | 2003-12-29 | 2006-12-14 | 세프라코 아이엔시. | 피롤 및 피라졸 디에이에이오 억제제 |
PL1828167T3 (pl) * | 2004-06-04 | 2015-02-27 | Debiopharm Int Sa | Pochodne akryloamidu jako środki antybiotykowe |
WO2006021277A1 (en) | 2004-08-21 | 2006-03-02 | Merck Patent Gmbh | MONOMERS, OLIGOMERS AND POLYMERS OF THIENO[2,3-b]THIOPHENE |
US7973060B2 (en) | 2005-10-13 | 2011-07-05 | Crystalgenomics, Inc. | Fab I inhibitor and process for preparing same |
KR20080075027A (ko) * | 2005-12-05 | 2008-08-13 | 아피늄 파마슈티컬스, 인크. | Fabi 억제제 및 항박테리아제로서의헤테로시클릴아크릴아미드 화합물 |
EP1976513B1 (en) | 2006-01-06 | 2016-08-24 | Sunovion Pharmaceuticals Inc. | Cycloalkylamines as monoamine reuptake inhibitors |
EP1978961B1 (en) | 2006-01-06 | 2016-03-16 | Sunovion Pharmaceuticals Inc. | Tetralone-based monoamine reuptake inhibitors |
WO2007086584A1 (ja) * | 2006-01-30 | 2007-08-02 | Meiji Seika Kaisha, Ltd. | 新規FabKおよびFabI/K阻害剤 |
DK2816024T3 (en) | 2006-03-31 | 2017-10-30 | Sunovion Pharmaceuticals Inc | CHIRALE AMINER |
US7884124B2 (en) | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
EP2687533B1 (en) * | 2006-07-20 | 2017-07-19 | Debiopharm International SA | Acrylamide derivatives as FAB I inhibitors |
US7902252B2 (en) | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
EP3255045A1 (en) | 2007-02-16 | 2017-12-13 | Debiopharm International SA | Salts, prodrugs and polymorphs of fab i inhibitors |
MX2009012685A (es) | 2007-05-31 | 2009-12-14 | Sepracor Inc | Cicloalquilaminas sustituidas con fenilo como inhibidores de la reabsorcion de monoamina. |
EP2014287A1 (de) * | 2007-06-13 | 2009-01-14 | Bayer Schering Pharma Aktiengesellschaft | Verwendung von Zimtsäurederivaten als Modulatoren des EP2-Rezeptors |
EP2286808A1 (en) * | 2009-08-18 | 2011-02-23 | Rheinische Friedrich-Wilhelms Universität | Cytohesin inhibitors |
KR20130010456A (ko) | 2009-11-18 | 2013-01-28 | 에프에이비 파마 에스에이에스 | 신규의 헤테로사이클릭 아크릴아미드 및 약제로서 이의 용도 |
WO2011156811A2 (en) * | 2010-06-11 | 2011-12-15 | Affinium Pharmaceuticals, Inc. | Compounds for treatment of bovine mastitis |
MY182666A (en) | 2010-11-05 | 2021-01-28 | Senomyx Inc | Compounds useful as modulators of trpm8 |
AR088729A1 (es) * | 2011-03-29 | 2014-07-02 | Actelion Pharmaceuticals Ltd | Derivados de 3-ureidoisoquinolin-8-ilo y una composicion farmaceutica |
CN102675311A (zh) * | 2011-06-14 | 2012-09-19 | 苏春华 | 一种氟代丙烯酰胺的衍生物 |
US9394295B2 (en) | 2011-08-10 | 2016-07-19 | Janssen Sciences Ireland Uc | Antibacterial homopiperidinyl substituted 3,4-dihydro-1H-[1,8]naphthyridinones |
ES2881681T3 (es) | 2011-08-10 | 2021-11-30 | Janssen Sciences Ireland Unlimited Co | 3,4-Dihidro-1H-[1,8]naftiridinonas sustituidas con piperidinilo antibacterianas |
JO3611B1 (ar) | 2011-08-10 | 2020-08-27 | Janssen Sciences Ireland Uc | سايكلو بنتا (سي (بيرول 4,3 ثاني هيدرو 1 hمستبدله [8,1] نافثيريدينونات مضادة للجراثيم |
EP3330269B1 (en) * | 2011-09-19 | 2023-06-07 | Kumar, Ajay | Heterocyclic compounds as inhibitors of fatty acid biosynthesis for bacterial infections |
US9062075B2 (en) | 2011-12-02 | 2015-06-23 | Aurigene Discovery Technologies Limited | Tetrahydropyridine derivatives as FabI inhibitors |
SG11201402409UA (en) | 2011-12-02 | 2014-10-30 | Aurigene Discovery Tech Ltd | Substituted pyridine derivatives as fabi inhibitors |
WO2013190384A1 (en) | 2012-06-19 | 2013-12-27 | Affinium Pharmaceuticals, Inc. | Prodrug derivatives of (e)-n-methyl-n-((3-methylbenzofuran-2-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide |
JP6250668B2 (ja) | 2012-08-10 | 2017-12-20 | ヤンセン・サイエンシズ・アイルランド・ユーシー | 新しい抗菌化合物 |
JP6250667B2 (ja) | 2012-08-10 | 2017-12-20 | ヤンセン・サイエンシズ・アイルランド・ユーシー | 新しい抗菌化合物 |
WO2014072930A2 (en) * | 2012-11-09 | 2014-05-15 | Aurigene Discovery Technologies Limited | Fused pyridine derivatives as antibacterial agents |
WO2014195844A1 (en) | 2013-06-04 | 2014-12-11 | Aurigene Discovery Technologies Limited | TETRAHYDROPYRIDINE DERIVATIVES AS FabI INHIBITORS |
DK3125883T3 (da) | 2014-04-04 | 2020-10-19 | Iomet Pharma Ltd | Indolderivater til anvendelse i medicin |
US10392371B2 (en) | 2015-10-01 | 2019-08-27 | Senomyx, Inc. | Compounds useful as modulators of TRPM8 |
CN105669519B (zh) * | 2016-01-04 | 2018-01-05 | 北方民族大学 | 吲哚类化合物、制备方法及其作为抗耐药菌药物的应用 |
PL3419628T3 (pl) | 2016-02-26 | 2021-05-31 | Debiopharm International Sa | Lek do leczenia zakażeń stopy cukrzycowej |
US10858319B2 (en) | 2016-10-03 | 2020-12-08 | Iomet Pharma Ltd. | Indole derivatives for use in medicine |
MX2020006587A (es) | 2017-12-22 | 2020-12-10 | Ravenna Pharmaceuticals Inc | Derivados de aminopiridina como inhibidores de fosfatidilinositol fosfato cinasa. |
WO2019177975A1 (en) * | 2018-03-12 | 2019-09-19 | The Board Of Trustees Of The University Of Illinois | Antibiotics effective for gram-negative pathogens |
WO2020099341A1 (en) | 2018-11-12 | 2020-05-22 | Debiopharm International S.A. | Antibiotic compounds, methods of manufacturing the same, pharmaceutical compositions containing the same and uses thereof |
Family Cites Families (122)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3828068A (en) | 1971-05-10 | 1974-08-06 | Tenneco Chem | ((substituted indazolyl)-n1-methyl)carbamates |
US4154943A (en) | 1977-12-29 | 1979-05-15 | University Of Vermont | Preparation of vincadifformine |
FR2619111B1 (fr) | 1987-08-07 | 1991-01-11 | Synthelabo | Derives de (piperidinyl-4)methyl-2 tetrahydro-1,2,3,4 9h-pyrido (3,4-b) indole, leur preparation et leur application en therapeutique |
CA2020437A1 (en) * | 1989-07-05 | 1991-01-06 | Yoshihide Fuse | Cinnamamide derivative |
HU210679B (en) | 1991-11-21 | 1995-06-28 | Richter Gedeon Vegyeszet | Process for producing new tetrahydro-pyrido/3,4-b/indol derivatives and pharmaceutical compositions containing the same |
FR2692575B1 (fr) | 1992-06-23 | 1995-06-30 | Sanofi Elf | Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant. |
US5416193A (en) * | 1993-04-30 | 1995-05-16 | Pfizer Inc. | Coupling reagent and method |
MA23420A1 (fr) | 1994-01-07 | 1995-10-01 | Smithkline Beecham Corp | Antagonistes bicycliques de fibrinogene. |
US5614551A (en) | 1994-01-24 | 1997-03-25 | The Johns Hopkins University | Inhibitors of fatty acid synthesis as antimicrobial agents |
MX9700041A (es) | 1994-06-29 | 1997-04-30 | Smithkline Beecham Corp | Antagonistas de receptor de vitronectina. |
US6176842B1 (en) | 1995-03-08 | 2001-01-23 | Ekos Corporation | Ultrasound assembly for use with light activated drugs |
US5989832A (en) * | 1995-04-21 | 1999-11-23 | Microcide Pharmaceuticals, Inc. | Method for screening for non-tetracycline efflux pump inhibitors |
EP0824535B1 (en) | 1995-05-11 | 2003-02-26 | Biochemie Gesellschaft M.B.H. | Antibacterial cephalosporins |
US6057291A (en) | 1995-06-02 | 2000-05-02 | University Of British Columbia | Antimicrobial cationic peptides |
HU227821B1 (en) | 1996-02-29 | 2012-03-28 | Astellas Pharma Inc | Tablets containing beta-lactam antibiotic and process for producing the same |
US6239154B1 (en) | 1996-03-08 | 2001-05-29 | Adolor Corporation | Kappa agonist compounds pharmaceutical formulations and method of prevention and treatment of pruritus therewith |
US6367985B1 (en) | 1996-03-12 | 2002-04-09 | Intellectual Property Company | Optical connector using large diameter alignment features |
DE19624659A1 (de) * | 1996-06-20 | 1998-01-08 | Klinge Co Chem Pharm Fab | Neue Pyridylalken- und Pyridylalkinsäureamide |
US6451816B1 (en) | 1997-06-20 | 2002-09-17 | Klinge Pharma Gmbh | Use of pyridyl alkane, pyridyl alkene and/or pyridyl alkine acid amides in the treatment of tumors or for immunosuppression |
US6503881B2 (en) | 1996-08-21 | 2003-01-07 | Micrologix Biotech Inc. | Compositions and methods for treating infections using cationic peptides alone or in combination with antibiotics |
US6995254B1 (en) | 1996-08-28 | 2006-02-07 | Affinium Pharmaceuticals, Inc. | Polynucleotide encoding the enoyl-acyl carrier protein reductase of Staphylococcus aureus, FAB I |
EA001526B1 (ru) | 1996-09-20 | 2001-04-23 | Мейдзи Сейка Кайся Лтд. | Кристаллическое вещество цефдиторен пивоксил и его получение |
US6521408B1 (en) | 1997-09-25 | 2003-02-18 | National Institute Of Agrobiological Sciences | Method for assessing a function of a gene |
DE19641437A1 (de) | 1996-10-08 | 1998-04-09 | Basf Ag | 1,3-Bis-(N-lactamyl)propane und deren pharmazeutische und kosmetische Verwendung |
DE19652239A1 (de) * | 1996-12-16 | 1998-06-18 | Bayer Ag | Verwendung von 7-(2-Oxa-5,8-diazabicyclo[4.3.0]non-8-yl)-chinolon- und -naphthyridoncarbonsäure-Derivaten zur Therapie von Helicobacter-pylori-Infektionen und den damit assoziierten gastroduodenalen Erkrankungen |
SI9600371B (sl) | 1996-12-18 | 2005-04-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Etilidenski derivati tricikličnih karbapenemov |
WO1998043969A1 (en) | 1997-03-31 | 1998-10-08 | Dupont Pharmaceuticals Company | Indazoles of cyclic ureas useful as hiv protease inhibitors |
AR012304A1 (es) | 1997-04-01 | 2000-10-18 | Borody Thomas J | Composiciones y metodos para el tratamiento de enfermedades intestinales inflamatorias y el uso de dicha composicion para preparar medicamentos paradichos tratamientos. |
US6406880B1 (en) | 1997-05-02 | 2002-06-18 | Integrated Research Technology, Llc | Betaines as adjuvants to susceptibility testing and antimicrobial therapy |
US6184363B1 (en) | 1997-06-13 | 2001-02-06 | Northwestern University | Inhibitors of β-lactamases and uses therefor |
US6207679B1 (en) | 1997-06-19 | 2001-03-27 | Sepracor, Inc. | Antimicrobial agents uses and compositions related thereto |
KR20010014105A (ko) * | 1997-06-23 | 2001-02-26 | 가마쿠라 아키오 | 헬리코박터 감염에 기인한 질환의 예방 또는 치료제 |
AUPO758297A0 (en) | 1997-06-27 | 1997-07-24 | Rowe, James Baber | Control of acidic gut syndrome |
US6198000B1 (en) * | 1997-07-07 | 2001-03-06 | Pfizer Inc. | Intermediates useful in the synthesis of quinoline antibiotics |
AU737018B2 (en) | 1997-07-25 | 2001-08-09 | Tsumura & Co. | Pyridylacrylamide derivatives and nephritis remedies and TGF-beta inhibitors containing the same |
HN1998000106A (es) * | 1997-08-01 | 1999-01-08 | Pfizer Prod Inc | Composiciones parenterales de alatroflaxacino |
US5932743A (en) | 1997-08-21 | 1999-08-03 | American Home Products Corporation | Methods for the solid phase synthesis of substituted indole compounds |
GB9717804D0 (en) * | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
SK88599A3 (en) | 1997-10-31 | 2000-03-13 | Novartis Ag | Glyphosate resistant transgenic plants |
US6432444B1 (en) | 1997-10-31 | 2002-08-13 | New Horizons Diagnostics Corp | Use of bacterial phage associated lysing enzymes for treating dermatological infections |
CA2309121A1 (en) * | 1997-11-07 | 1999-05-20 | Schering Corporation | Phenyl-alkyl-imidazoles as h3 receptor antagonists |
SE9704404D0 (sv) | 1997-11-28 | 1997-11-28 | Astra Ab | New compounds |
GB9725244D0 (en) | 1997-11-29 | 1998-01-28 | Zeneca Ltd | Chemical compounds |
DE19753298A1 (de) | 1997-12-01 | 1999-06-02 | Basf Ag | Verfahren zur Herstellung von festen Dosierungsformen |
CZ302082B6 (cs) | 1998-01-07 | 2010-09-29 | Meiji Seika Kaisha Ltd. | Prostredek zahrnující krystalograficky stabilní amorfní cefalosporin a zpusob jeho výroby |
US6184380B1 (en) * | 1999-01-25 | 2001-02-06 | Pfizer Inc. | Process for preparing naphthyridones and intermediates |
PA8466701A1 (es) * | 1998-01-21 | 2000-09-29 | Pfizer Prod Inc | Comprimido de mesilato de trovafloxacino |
US6204279B1 (en) | 1998-06-03 | 2001-03-20 | Microcide Pharmaceuticals, Inc. | Peptidomimetic efflux pump inhibitors |
RU2241489C2 (ru) | 1998-02-27 | 2004-12-10 | Биора Биоэкс Аб | Композиции матриксных протеинов для залечивания ран |
US6350738B1 (en) | 1998-03-06 | 2002-02-26 | Brigham Young University | Steroid derived antibiotics |
DE19820801A1 (de) | 1998-05-09 | 1999-11-25 | Gruenenthal Gmbh | Orale Arzneiformen mit reproduzierbarer Wirkstofffreisetzung von Gatifloxacin oder pharmazeutisch verwendbaren Salzen oder Hydraten |
DE19821039A1 (de) * | 1998-05-11 | 1999-11-18 | Bayer Ag | Verfahren zur Herstellung von (S,S)-Benzyl-2,8-diazabicyclo[4.3.0]nonan |
US6399629B1 (en) | 1998-06-01 | 2002-06-04 | Microcide Pharmaceuticals, Inc. | Efflux pump inhibitors |
US6428579B1 (en) | 1998-07-01 | 2002-08-06 | Brown University Research Foundation | Implantable prosthetic devices coated with bioactive molecules |
US6423741B1 (en) | 1998-07-10 | 2002-07-23 | Council Of Scientific And Industrial Research | Anti-microbial composition and method for producing the same |
GB9815567D0 (en) | 1998-07-18 | 1998-09-16 | Glaxo Group Ltd | Antiviral compound |
PT1101497E (pt) | 1998-08-04 | 2008-04-23 | Schering Plough Animal Health | Preparações oleosas estabilizadas de tobicilina (antibiótico beta-lactâmico) |
CN1133432C (zh) | 1998-08-21 | 2004-01-07 | 千寿制药株式会社 | 含水液体药物组合物 |
US6461607B1 (en) | 1998-08-24 | 2002-10-08 | Ganeden Biotech, Inc. | Probiotic, lactic acid-producing bacteria and uses thereof |
US6518487B1 (en) | 1998-09-23 | 2003-02-11 | Pioneer Hi-Bred International, Inc. | Cyclin D polynucleotides, polypeptides and uses thereof |
US6509327B1 (en) | 1998-09-30 | 2003-01-21 | Alcon Manufacturing, Ltd. | Compositions and methods for treating otic, ophthalmic and nasal infections |
US6395746B1 (en) | 1998-09-30 | 2002-05-28 | Alcon Manufacturing, Ltd. | Methods of treating ophthalmic, otic and nasal infections and attendant inflammation |
TW526202B (en) | 1998-11-27 | 2003-04-01 | Shionogi & Amp Co | Broad spectrum cephem having benzo[4,5-b]pyridium methyl group of antibiotic activity |
US6515113B2 (en) | 1999-02-18 | 2003-02-04 | The Regents Of The University Of California | Phthalamide lanthanide complexes for use as luminescent markers |
US6294192B1 (en) | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US6267985B1 (en) | 1999-06-30 | 2001-07-31 | Lipocine Inc. | Clear oil-containing pharmaceutical compositions |
US6248363B1 (en) | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
AU3615200A (en) | 1999-03-03 | 2000-09-21 | Princeton University | Bacterial transglycosylases: assays for monitoring the activity using lipid ii substrate analogs and methods for discovering new antibiotics |
US6495161B1 (en) | 1999-03-09 | 2002-12-17 | Vivorx, Inc. | Cytoprotective biocompatible containment systems for biologically active materials and methods of making same |
US6239113B1 (en) | 1999-03-31 | 2001-05-29 | Insite Vision, Incorporated | Topical treatment or prevention of ocular infections |
US6448054B1 (en) | 1999-04-08 | 2002-09-10 | The General Hospital Corporation | Purposeful movement of human migratory cells away from an agent source |
CO5180550A1 (es) * | 1999-04-19 | 2002-07-30 | Smithkline Beecham Corp | Inhibidores de fab i |
US6290946B1 (en) | 1999-05-13 | 2001-09-18 | Geltex Pharmaceuticals, Inc. | Anionic polymers as toxin binders and antibacterial agents |
US6514535B2 (en) | 1999-05-21 | 2003-02-04 | Noveon Ip Holdings Corp. | Bioadhesive hydrogels with functionalized degradable crosslinks |
AR024077A1 (es) * | 1999-05-25 | 2002-09-04 | Smithkline Beecham Corp | Compuestos antibacterianos |
CO5370679A1 (es) * | 1999-06-01 | 2004-02-27 | Smithkline Beecham Corp | Inhibidores fab 1 |
US6239141B1 (en) | 1999-06-04 | 2001-05-29 | Pfizer Inc. | Trovafloxacin oral suspensions |
CO5180605A1 (es) * | 1999-06-23 | 2002-07-30 | Smithkline Beecham Corp | Compuestos de indol |
CO5190665A1 (es) * | 1999-06-23 | 2002-08-29 | Smithkline Beecham Corp | Compuestos de indol |
CA2282066C (en) | 1999-06-29 | 2010-09-07 | Smithkline Beecham Corporation | Methods of use of quinolone compounds against atypical upper respiratory pathogenic bacteria |
US6309663B1 (en) | 1999-08-17 | 2001-10-30 | Lipocine Inc. | Triglyceride-free compositions and methods for enhanced absorption of hydrophilic therapeutic agents |
US6500459B1 (en) | 1999-07-21 | 2002-12-31 | Harinderpal Chhabra | Controlled onset and sustained release dosage forms and the preparation thereof |
US6346391B1 (en) | 1999-07-22 | 2002-02-12 | Trustees Of Tufts College | Methods of reducing microbial resistance to drugs |
AU6925500A (en) * | 1999-08-23 | 2001-03-19 | Smithkline Beecham Corporation | Fatty acid synthase inhibitors |
EP1212093B1 (en) | 1999-08-26 | 2004-07-07 | Ganeden Biotech, Inc. | Use of emu oil as a carrier for antifungal, antibacterial and antiviral medications |
US6221859B1 (en) * | 1999-08-27 | 2001-04-24 | Merck & Co., Inc. | Carbapenem antibacterial compositions and methods of the treatment |
US6174878B1 (en) * | 1999-08-31 | 2001-01-16 | Alcon Laboratories, Inc. | Topical use of kappa opioid agonists to treat otic pain |
US6503955B1 (en) | 1999-09-11 | 2003-01-07 | The Procter & Gamble Company | Pourable liquid vehicles |
JP4745573B2 (ja) | 1999-09-17 | 2011-08-10 | マルホ株式会社 | 抗菌医薬組成物 |
US6500463B1 (en) | 1999-10-01 | 2002-12-31 | General Mills, Inc. | Encapsulation of sensitive components into a matrix to obtain discrete shelf-stable particles |
JP4961084B2 (ja) | 1999-10-08 | 2012-06-27 | アフィニアム・ファーマシューティカルズ・インコーポレイテッド | Fabi阻害剤 |
ES2231275T3 (es) | 1999-10-08 | 2005-05-16 | Affinium Pharmaceuticals, Inc. | Inhibidores de fab i. |
EP1225894B1 (en) | 1999-10-08 | 2006-07-05 | Affinium Pharmaceuticals, Inc. | Fab i inhibitors |
US6762201B1 (en) * | 1999-10-08 | 2004-07-13 | Affinium Pharmaceuticals, Inc. | Fab I inhibitors |
US6730684B1 (en) * | 1999-10-08 | 2004-05-04 | Affinium Pharmaceuticals, Inc. | Fab I inhibitors |
US6503908B1 (en) | 1999-10-11 | 2003-01-07 | Pfizer Inc | Pharmaceutically active compounds |
WO2001029035A1 (fr) | 1999-10-19 | 2001-04-26 | Sato Pharmaceutical Co., Ltd. | Antimicrobiens 4-oxoquinolizine presentant des squelettes 2-pyridone en tant que structure partielle |
US6951729B1 (en) | 1999-10-27 | 2005-10-04 | Affinium Pharmaceuticals, Inc. | High throughput screening method for biological agents affecting fatty acid biosynthesis |
PT1666028E (pt) | 1999-10-29 | 2010-06-15 | Novartis Ag | Composições de pós anidros com melhor dispersividade |
US6531291B1 (en) | 1999-11-10 | 2003-03-11 | The Trustees Of Columbia University In The City Of New York | Antimicrobial activity of gemfibrozil and related compounds and derivatives and metabolites thereof |
US6514986B2 (en) | 2000-11-22 | 2003-02-04 | Wockhardt Limited | Chiral fluoroquinolone arginine salt forms |
US6656703B1 (en) | 1999-12-29 | 2003-12-02 | Millennium Pharamaceuticals, Inc. | High throughput screen for inhibitors of fatty acid biosynthesis in bacteria |
US6372752B1 (en) | 2000-02-07 | 2002-04-16 | Genzyme Corporation | Inha inhibitors and methods of use thereof |
WO2001072317A1 (en) | 2000-03-28 | 2001-10-04 | Council Of Scientific And Industrial Research | Formulation comprising thymol useful in the treatment of drug resistant bacterial infections |
JP2003531184A (ja) | 2000-04-21 | 2003-10-21 | ローディア/カイレックス・インコーポレイテッド | (r)−1−(アリールオキシ)プロパン−2−オールの製造方法 |
AU8298801A (en) | 2000-07-26 | 2002-02-05 | John K Vyden | Methods for treating atopic disorders |
US6288239B1 (en) | 2000-09-19 | 2001-09-11 | Board Of Trustees Operating Michigan State University | 5-trityloxymethyl-oxazolidinones and process for the preparation thereof |
US7048926B2 (en) * | 2000-10-06 | 2006-05-23 | Affinium Pharmaceuticals, Inc. | Methods of agonizing and antagonizing FabK |
US6821746B2 (en) | 2000-10-06 | 2004-11-23 | Affinium Pharmaceuticals, Inc. | Methods of screening for FabK antagonists and agonists |
AU2002227269A1 (en) | 2000-11-07 | 2002-06-03 | Bristol-Myers Squibb Company | Acid derivatives useful as serine protease inhibitors |
AU2002232558A1 (en) | 2000-12-12 | 2002-06-24 | Corvas International, Inc. | Compounds, compositions and methods for treatment of parasitic infections |
US6388070B1 (en) | 2001-01-05 | 2002-05-14 | Orchid Chemicals & Pharmaceuticals Ltd. | Thioester derivatives of thiazolyl acetic acid and their use in the preparation of cephalosporin compounds |
US6495158B1 (en) | 2001-01-19 | 2002-12-17 | Lec Tec Corporation | Acne patch |
DE60230934D1 (de) | 2001-04-06 | 2009-03-05 | Affinium Pharm Inc | Fab-i-inhibitoren |
US6573941B1 (en) * | 2002-04-22 | 2003-06-03 | Thomson Licensing Sa | Low bit rate compression format conversion for improved resolution |
US6503906B1 (en) | 2002-02-21 | 2003-01-07 | Ren-Jin Lee | Method for optimizing ciprofloxacin treatment of anthrax-exposed patients according to the patient's characteristics |
ES2518316T3 (es) | 2002-12-06 | 2014-11-05 | Debiopharm International Sa | Compuestos heterocíclicos, métodos de fabricación de los mismos y su uso en terapia |
DE602004016831D1 (de) * | 2003-03-17 | 2008-11-13 | Affinium Pharm Inc | Pharmazeutische zusammensetzungen inhibitoren von fab i und weitere antibiotika enthaltend |
PL1828167T3 (pl) | 2004-06-04 | 2015-02-27 | Debiopharm Int Sa | Pochodne akryloamidu jako środki antybiotykowe |
KR20080075027A (ko) | 2005-12-05 | 2008-08-13 | 아피늄 파마슈티컬스, 인크. | Fabi 억제제 및 항박테리아제로서의헤테로시클릴아크릴아미드 화합물 |
EP2687533B1 (en) | 2006-07-20 | 2017-07-19 | Debiopharm International SA | Acrylamide derivatives as FAB I inhibitors |
EP3255045A1 (en) | 2007-02-16 | 2017-12-13 | Debiopharm International SA | Salts, prodrugs and polymorphs of fab i inhibitors |
-
2000
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