Title: N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: synthesis and biological evaluation.

Abstract: A group of N-1 and C-3 disubstituted-indole Schiff bases bearing an indole N-1 (R'=H, CH(2)Ph, COPh) substituent in conjunction with a C-3 -C=HN-C(6)H(4)-4-X (X=F, Me, CF(3), Cl) substituent were synthesized and evaluated as inhibitors of cyclooxygenase (COX) isozymes (COX-1/COX-2). Within this group of Schiff bases, compounds 15 (R(1)=CH(2)Ph, X=F), 17 (R(1)=CH(2)Ph, X=CF(3)), 18 (R(1)=COPh, X=F) and 20 (R(1)=COPh, X=CF(3)) were identified as effective and selective COX-2 inhibitors (COX-2 IC(50)'s=0.32-0.84 ##M range; COX-2 selectivity index (SI)=113 to >312 range). 1-Benzoyl-3-[(4-trifluoromethylphenylimino)methyl]indole (20) emerged as the most potent (COX-1 IC(50) >100 ##M; COX-2 IC(50)=0.32 ##M) and selective (SI >312) COX-2 inhibitor. Furthermore, compound 20 is a selective COX-2 inhibitor in contrast to the reference drug indomethacin that is a potent and selective COX-1 inhibitor (COX-1 IC(50)=0.13 ##M; COX-2 IC(50)=6.9 ##M, COX-2 SI=0.02). Molecular modeling studies employing compound 20 showed that the phenyl CF(3) substituent attached to the CN spacer is positioned near the secondary pocket of the COX-2 active site, the CN nitrogen atom is hydrogen bonded (N######NH=2.85 #
(PMID: 22361134)

Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 17047

ChEMBL target type: Target is a single protein chain