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BioAssay: AID 637687

Clearance in human 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(22)
 
 
Inconclusive(5)
 
 
Unspecified(17)
 
 
 Tested Substances
 Tested Substances
All(22)
 
 
Inconclusive(5)
 
 
Unspecified(17)
 
 
 Related BioAssays
 Related BioAssays
AID: 637687
Data Source: ChEMBL (795135)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-09-09
Modify Date: 2014-08-23

Data Table ( Complete ):           View All Data
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: 102164
Target Type: SUBCELLULAR
Pref Name: Liver microsomes
Organism: Homo sapiens
Tax ID: 9606
Confidence: Target assigned is subcellular fraction
Relationship Type: Subcellular target assigned
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: ADME
Assay Data Source: Scientific Literature
Assay Test Type: In vitro
Assay Subcellular Fraction: Microsomes
Assay Tissue: Liver
Result Definitions
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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
6CLH activity commentCLH activity commentString
7CLH standard flagCLH standard flagInteger
8CLH qualifierCLH qualifierString
9CLH published valueCLH published valueFloat
10CLH standard valueCLH standard valueFloat

Data Table (Concise)
Data Table ( Complete ):     View All Data
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