BDBM50427655 DESCHLOROBENZOYL INDOMETHACIN
BDBM29345 Indomethacin-amide derivative, 15
BDBM29346 Indomethacin-amide derivative, 16
BDBM29347 Indomethacin-amide derivative, 19
BDBM29348 Indomethacin-amide derivative, 18
BDBM29349 Indomethacin-amide derivative, 20
BDBM29350 Indomethacin-amide derivative, 21
BDBM29351 Indomethacin-amide derivative, 22
Indomethacin-amide derivative, 13 BDBM29343
Indomethacin-amide derivative, 14 BDBM29344
2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid CHEMBL6 US11478464, Compound Indomethacin BDBM17638 Indocin US9271961, Indomethacin indometacin Indomethacin
2'-des-methyl indomethacin BDBM50293598 CHEMBL503179 US9346803, Des-methylIndomethacin
CHEMBL95921 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetamide BDBM22965 Indomethacin derivative, 18
2-[1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-methoxy-acetamide(Indomethacin series) CHEMBL65130 BDBM50012891
CHEMBL318495 Indomethacin derivative, 4 BDBM22951 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-methylacetamide
CHEMBL320140 2-{1-[(4-bromophenyl)methyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetic acid BDBM22970 Indomethacin derivative, 23
Indomethacin derivative, 5 BDBM22952 CHEMBL73572 methyl 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate
BDBM22955 4-methoxyphenyl 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate CHEMBL316866 Indomethacin derivative, 8
BDBM22958 CHEMBL318881 Indomethacin derivative, 11 4-fluorophenyl 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate
BDBM22967 Indomethacin derivative, 20 CHEMBL95643 2-phenylethyl 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate
BDBM22969 CHEMBL316484 2-phenylethyl 2-{1-[(4-bromophenyl)methyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate Indomethacin derivative, 22
[1-(4-Chloro-benzoyl)-5-hydroxy-2-methyl-1H-indol-3-yl]-acetic acid CHEMBL6 [1-(4-Chloro-benzoyl)-5-hydroxy-2-methyl-1H-indol-3-yl]-acetic acid( Indomethacin) BDBM50029074 2-{1-[(4-chlorophenyl)carbonyl]-5-hydroxy-2-methylindol-3-yl}acetic acid DESMETHYL INDOMETHACIN
2-[1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-hydroxy-N-methyl-acetamide(Indomethacin series) CHEMBL65490 BDBM50012889
2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-(4-fluorophenyl)acetamide BDBM22961 CHEMBL421570 Indomethacin derivative, 14
BDBM22956 4-(methylsulfanyl)phenyl 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate CHEMBL96057 Indomethacin derivative, 9
BDBM22966 Indomethacin derivative, 19 CHEMBL95311 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-(2-phenylethyl)acetamide
BDBM50012892 2-[1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-hydroxy-N-isopropyl-acetamide(Indomethacin series) CHEMBL303199
CHEMBL95625 Indomethacin derivative, 10 BDBM22957 2-(methylsulfanyl)phenyl 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate
CHEMBL96954 pyridin-3-yl 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}acetate Indomethacin derivative, 12 BDBM22959
Indomethacin derivative, 21 BDBM22968 CHEMBL319999 2-{1-[(4-bromophenyl)methyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-(2-phenylethyl)acetamide
Indomethacin derivative, 6 BDBM22953 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-(2-hydroxyethyl)acetamide CHEMBL24415
Indomethacin derivative, 7 CHEMBL95469 BDBM22954 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-(4-acetamidophenyl)acetamide
BDBM22960 CHEMBL96011 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[4-(methylsulfanyl)phenyl]acetamide Indomethacin derivative, 13
BDBM22964 Indomethacin derivative, 17 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-methyl-N-(2-phenylethyl)acetamide CHEMBL97042
BDBM22963 Indomethacin derivative, 16 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-1-(piperidin-1-yl)ethan-1-one CHEMBL95052
CHEMBL329480 JMC522846 Compound 12 BDBM22962 Indomethacin derivative, 15 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-(pyridin-3-yl)acetamide
2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[(2R)-1-hydroxybutan-2-yl]acetamide CHEMBL24957 alpha-substituted indomethacin ethanolamide, 8 BDBM22572
BDBM22569 alpha-substituted indomethacin ethanolamide, 6 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[(2R)-1-hydroxypropan-2-yl]acetamide CHEMBL24874
CHEMBL26509 alpha-substituted indomethacin ethanolamide, 16 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[(1R)-2-hydroxy-1-phenylethyl]acetamide BDBM22576
CHEMBL277006 BDBM22577 alpha-substituted indomethacin ethanolamide, 17 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[(1S)-2-hydroxy-1-phenylethyl]acetamide
CHEMBL27784 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[(2S)-1-hydroxybutan-2-yl]acetamide alpha-substituted indomethacin ethanolamide, 9 BDBM22573
CHEMBL281847 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[(2S)-1-hydroxypropan-2-yl]acetamide alpha-substituted indomethacin ethanolamide, 7 BDBM22571
BDBM22574 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[(2R)-1-hydroxy-4-(methylsulfanyl)butan-2-yl]acetamide CHEMBL432260 alpha-substituted indomethacin ethanolamide, 14
CHEMBL281379 BDBM22575 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methyl-1H-indol-3-yl}-N-[(2S)-1-hydroxy-4-(methylsulfanyl)butan-2-yl]acetamide alpha-substituted indomethacin ethanolamide, 15
2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}-N-(3-hydroxypropyl)acetamide CHEMBL25725 2-[1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-(3-hydroxy-propyl)-acetamide Indomethacin 3-hydroxypropylamide BDBM50112548
2-[1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-hydroxy-acetamide 2-[1-(4-Chloro-benzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]-N-hydroxy-acetamide(Indomethacin series) 2-{1-[(4-chlorophenyl)carbonyl]-5-methoxy-2-methylindol-3-yl}ethanehydroxamic acid BDBM50012893 Oxametacin CHEMBL295829
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- COX Inhibitor Screening Assay The COX enzyme activities were measured using the COX Inhibitor Screening Assay kit provided by Cayman (Cayman, Chemical Co., Ann Arbor, MI). The assay directly measures PGF2a produced by SnCl2 reduction of COX-derived PGH2. The prostanoid production was quantified via enzyme immunoassay using a broadly specific antibody that binds to all the major prostaglandin compounds. IC50 values were calculated for the most active compounds. Naproxen and indomethacin were used as the positive controls.
- Inhibition Assay The cells expressing mouse EP1 receptor were seeded at 104 cells/well in 96-well plates and cultured for 2 days with 10% Fetal Bovine Serum (FBS)/alpha Modified Eagle Medium (alphaMEM) in the incubator (37° C., 5% CO2). The cells were washed with phosphate buffer, and load buffer (10% FBS/αMEM containing Fura2/AM (5 uM), indomethacin (20 uM) and probenecid (2.5 mM)) was then added to each well and cells were left standing for 1 hour. Load buffer of each well was discarded and assay buffer (Hank's Balanced Salt Solution (HBSS) containing indomethacin (2.5 mM), probenecid (2.5 mM), HEPES-NaOH (10 mM) and 0.1% (w/v) Bovine Serum Albumin (BSA)) was added to each well and plates were left at room temperature in a dark room for 1 hour. Afterwards, compounds of the present invention (10 uL) or PGE2 (10 uL) prepared with assay buffer was added to each well and intracellular calcium concentrations were measured using a Fluorescence Drug Screening System.
- In Vitro COX Inhibition Assay Inhibitory activity of the synthesized compounds on COX-1 and COX-2 enzymes were evaluated at 40 μm using the COX Inhibitor Screening Assay Kit (Cayman No: 560101) according to the protocol recommended by the supplier. The test compounds were dissolved in dimethyl sulphoxide. Celecoxib and indomethacin were used as reference drugs. COX catalyzes the first step in the biosynthesis of AA to PGH2. The PGF2a produced from PGH2 by reduction with stannous chloride produced in the COX reaction. The prostanoid product is quantified by EIA using a broadly specific antiserum that binds to all the major PG compounds. The product of the enzymatic reaction has a distinct yellow color and absorbs strongly at 412 nm.
- In Vitro Binding Assay hEP1 and hEP4 membranes are prepared from recombinant HEK293 cells stably expressing human EP1 (Genbank accession number AY275470) or EP4 (Genbank accession number AY429109) receptors. hEP2 and hEP3 membranes are prepared from HEK293 cells transiently transfected with EP2 (Genbank accession number AY275471) or EP3 (isoform VI: Genbank accession number AY429108) receptor plasmids. Frozen cell pellets are homogenized in homogenization buffer using a Teflon/glass homogenizer. Membrane protein is aliquoted and quick frozen on dry ice prior to storage at -80 C. Homogenization buffer contained 10 mM Tris-HCl, pH 7.4, 250 mM sucrose, 1 mM EDTA, 0.3 mM indomethacin and plus Complete, with EDTA, obtained from Roche Molecular Biochemicals (Catalog Number 1 697 498). Kd values for [3H]-PGE2 binding to each receptor are determined by saturation binding studies or homologous competition. Compounds are tested in a 96-well format using a three-fold dilution series to generate a 10-point curve.
- In Vitro Binding Assay hEP1 and hEP4 membranes are prepared from recombinant HEK293 cells stably expressing the human EP1 (Genbank accession number AY275470) or EP4 (Genbank accession number AY429109) receptors. hEP2 and hEP3 membranes are prepared from HEK293 cells transiently transfected with EP2 (Genbank accession number AY275471) or EP3 (isoform VI: Genbank accession number AY429108) receptor plasmids. Frozen cell pellets are homogenized in homogenization buffer using a Teflon/glass homogenizer. Membrane protein is aliquoted and quick frozen on dry ice prior to storage at -80 C. Homogenization buffer contained 10 mM Tris-HCl, pH 7.4, 250 mM sucrose, 1 mM EDTA, 0.3 mM indomethacin and plus Complete, with EDTA, obtained from Roche Molecular Biochemicals (Catalog Number 1 697 498).Kd values for [3H]-PGE2 binding to each receptor are determined by saturation binding studies or homologous competition. Compounds are tested in a 96-well format using a three-fold dilution series.
- In Vitro Binding Assay hEP1 and hEP4 membranes are prepared from recombinant HEK293 cells stably expressing the human EP1 (Genbank accession number AY275470) or EP4 (Genbank accession number AY429109) receptors. hEP2 and hEP3 membranes are prepared from HEK293 cells transiently transfected with EP2 (Genbank accession number AY275471) or EP3 (isoform VI: Genbank accession number AY429108) receptor plasmids. Frozen cell pellets are homogenized in homogenization buffer using a Teflon/glass homogenizer. Membrane protein is aliquoted and quick frozen on dry ice prior to storage at -80 C. Homogenization buffer contained 10 mM Tris-HCl, pH 7.4, 250 mM sucrose, 1 mM EDTA, 0.3 mM indomethacin and plus Complete, with EDTA, obtained from Roche Molecular Biochemicals (Catalog Number 1 697 498).Kd values for [3]H-PGE2 binding to each receptor are determined by saturation binding studies or homologous competition. Compounds are tested in a 96-well format using a three-fold dilution series.