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BioAssay: AID 637693

Antidiabetic activity in po dosed fatty Wister rat assessed as reduction of plasma glucose level administered once daily for 7 days

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)
 
 
Inactive(1)
 
 
Unspecified(3)
 
 
 Tested Substances
 Tested Substances
All(4)
 
 
Inactive(1)
 
 
Unspecified(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 637693
Data Source: ChEMBL (795141)
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: 50597
Target Type: ORGANISM
Pref Name: Rattus norvegicus
Organism: Rattus norvegicus
Tax ID: 10116
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
Assay Type: Functional

Assay Data Source: Scientific Literature

BAO: Assay Format: organism-based format

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Activity activity commentActivity activity commentString
2Activity standard flagActivity standard flagInteger
3Activity qualifierActivity qualifierString
4Activity published valueActivity published valueFloat
5Activity standard valueActivity standard valueFloat
6ED25 activity commentED25 activity commentString
7ED25 standard flagED25 standard flagInteger
8ED25 qualifierED25 qualifierString
9ED25 published valueED25 published valueFloatmg kg-1
10ED25 standard valueED25 standard valueFloatmg kg-1

Data Table (Concise)
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