A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPAR## modulators (SPPAR##Ms) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPAR## full agonist drugs. Structure-activity relationships of more ..
Target
Tested Compounds:
Description:
Title: Benzimidazolones: a new class of selective peroxisome proliferator-activated receptor ## (PPAR##) modulators.
Abstract: A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPAR## modulators (SPPAR##Ms) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPAR## full agonist drugs. Structure-activity relationships of these potent and highly selective SPPAR##Ms were studied with a focus on their unique profiles as partial agonists or modulators. A variety of methods, such as X-ray crystallographic analysis, PPAR## transactivation coactivator profiling, gene expression profiling, and mutagenesis studies, were employed to reveal the differential interactions of these new analogues with PPAR## receptor in comparison to full agonists. In rodent models of T2DM, benzimidazolone analogues such as (5R)-5-(3-{[3-(5-methoxybenzisoxazol-3-yl)benzimidazol-1-yl]methyl}phenyl)-5-methyloxazolidinedione (51) demonstrated efficacy equivalent to that of rosiglitazone. Side effects, such as fluid retention and heart weight gain associated with PPAR## full agonists, were diminished with 51 in comparison to rosiglitazone based on studies in two independent animal models.
(PMID: 22070604)
Abstract: A series of benzimidazolone carboxylic acids and oxazolidinediones were designed and synthesized in search of selective PPAR## modulators (SPPAR##Ms) as potential therapeutic agents for the treatment of type II diabetes mellitus (T2DM) with improved safety profiles relative to rosiglitazone and pioglitazone, the currently marketed PPAR## full agonist drugs. Structure-activity relationships of these potent and highly selective SPPAR##Ms were studied with a focus on their unique profiles as partial agonists or modulators. A variety of methods, such as X-ray crystallographic analysis, PPAR## transactivation coactivator profiling, gene expression profiling, and mutagenesis studies, were employed to reveal the differential interactions of these new analogues with PPAR## receptor in comparison to full agonists. In rodent models of T2DM, benzimidazolone analogues such as (5R)-5-(3-{[3-(5-methoxybenzisoxazol-3-yl)benzimidazol-1-yl]methyl}phenyl)-5-methyloxazolidinedione (51) demonstrated efficacy equivalent to that of rosiglitazone. Side effects, such as fluid retention and heart weight gain associated with PPAR## full agonists, were diminished with 51 in comparison to rosiglitazone based on studies in two independent animal models.
(PMID: 22070604)
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 163
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 163
ChEMBL target type: Target is a single protein chain
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | IC50* | IC50 PubChem standard value |  | Float | μM | |
| 2 | IC50 activity comment | IC50 activity comment | String | |||
| 3 | IC50 standard flag | IC50 standard flag | | Integer | ||
| 4 | IC50 qualifier | IC50 qualifier | String | |||
| 5 | IC50 published value | IC50 published value | | Float | nM | |
| 6 | IC50 standard value | IC50 standard value | | Float | nM |
* Activity Concentration.
Data Table (Concise)
Classification
PageFrom: