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BioAssay: AID 649272

Dissociation constant, pKa of the compound

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, more ..
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 649272
Data Source: ChEMBL (806720)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2013-07-07

Data Table ( Complete ):           All
Tested Compound:
Description:
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 I(1/4)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 I(1/4)M; COX-2 IC(50)=0.32 I(1/4)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 I(1/4)M; COX-2 IC(50)=6.9 I(1/4)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 (NA.A.A.NH=2.85 A
(PMID: 22361134)
Comment
Putative Target:

ChEMBL Target ID: 22226
Target Type: UNCHECKED
Pref Name: Unchecked
Confidence: Default value - Target unknown or has yet to be assigned
Relationship Type: Default value - Target has yet to be curated
Categorized Comment
ChEMBL Assay Type: Unassigned

ChEMBL Assay Data Source: Scientific Literature

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1pKa activity commentpKa activity commentString
2pKa standard flagpKa standard flagInteger
3pKa qualifierpKa qualifierString
4pKa published valuepKa published valueFloat
5pKa standard valuepKa standard valueFloat

Data Table (Concise)
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