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BioAssay: AID 637694

Clearance in rat liver microsomes at 1 umol/L after 20 mins by HPLC analysis

Herein, we describe the design, synthesis, and structure-activity relationships of novel benzylpyrazole acylsulfonamides as non-thiazolidinedione (TZD), non-carboxylic-acid-based peroxisome proliferator-activated receptor (PPAR) gamma agonists. Docking model analysis of in-house weak agonist 2 bound to the reported PPARgamma ligand binding domain suggested that modification of the carboxylic acid more ..
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 Tested Compounds
 Tested Compounds
All(4)
 
 
Unspecified(4)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Unspecified(4)
 
 
 Related BioAssays
 Related BioAssays
AID: 637694
Data Source: ChEMBL (795142)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-05-25

Data Table ( Complete ):           All
Tested Compounds:
Description:
Title: A new class of non-thiazolidinedione, non-carboxylic-acid-based highly selective peroxisome proliferator-activated receptor (PPAR) gamma agonists: design and synthesis of benzylpyrazole acylsulfonamides.

Abstract: Herein, we describe the design, synthesis, and structure-activity relationships of novel benzylpyrazole acylsulfonamides as non-thiazolidinedione (TZD), non-carboxylic-acid-based peroxisome proliferator-activated receptor (PPAR) gamma agonists. Docking model analysis of in-house weak agonist 2 bound to the reported PPARgamma ligand binding domain suggested that modification of the carboxylic acid of 2 would help strengthen the interaction of 2 with the TZD pocket and afford non-carboxylic-acid-based agonists. In this study, we used an acylsulfonamide group as the ring-opening analog of TZD as an isosteric replacement of carboxylic acid moiety of 2; further, preliminary modification of the terminal alkyl chain on the sulfonyl group gave the lead compound 3c. Subsequent optimization of the resulting compound gave the potent agonists 25c, 30b, and 30c with high metabolic stability and significant antidiabetic activity. Further, we have described the difference in binding mode of the carboxylic-acid-based agonist 1 and acylsulfonamide 3d.
(PMID: 22209730)
Comment
Putative Target:

ChEMBL Target ID: 102178
Target Type: SUBCELLULAR
Pref Name: Liver microsomes
Organism: Rattus norvegicus
Tax ID: 10116
Confidence: Target assigned is subcellular fraction
Relationship Type: Subcellular target assigned
Categorized Comment
Assay Type: ADME

Assay Data Source: Scientific Literature

Assay Test Type: In vitro

BAO: Assay Format: subcellular format

Assay Tissue: Liver

Assay Subcellular Fraction: Microsomes

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1CL activity commentCL activity commentString
2CL standard flagCL standard flagInteger
3CL qualifierCL qualifierString
4CL published valueCL published valueFloatmicroL/min/mg
5CL standard valueCL standard valueFloatmL.min-1.g-1

Data Table (Concise)
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