The design, synthesis, and ability to inhibit p38## MAP kinase by a novel series of naphthyridine N-oxides will be described. Some of these compounds showed a significant reduction in the LPS-induced TNF## production in human whole blood. Structure-activity relationship studies revealed that N-oxide oxygen was essential for activity and was probably a determinant factor for its marked selectivity more ..
Target
Tested Compound:
Description:
Title: 1,7-Naphthyridine 1-oxides as novel potent and selective inhibitors of p38 mitogen activated protein kinase.
Abstract: The design, synthesis, and ability to inhibit p38## MAP kinase by a novel series of naphthyridine N-oxides will be described. Some of these compounds showed a significant reduction in the LPS-induced TNF## production in human whole blood. Structure-activity relationship studies revealed that N-oxide oxygen was essential for activity and was probably a determinant factor for its marked selectivity against other related kinases. After an extensive SAR exercise, several compounds from this series were identified as very potent p38## inhibitors. In vivo efficacy of some derivatives was demonstrated to reduce TNF## levels in an acute murine model of inflammation (ED(50) = 0.5 mg/kg in LPS-induced TNF## production when dosed orally 1.5 h prior to LPS administration). The oral efficacy was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally (ED(50) < 1 mg/kg).
(PMID: 21999461)
Abstract: The design, synthesis, and ability to inhibit p38## MAP kinase by a novel series of naphthyridine N-oxides will be described. Some of these compounds showed a significant reduction in the LPS-induced TNF## production in human whole blood. Structure-activity relationship studies revealed that N-oxide oxygen was essential for activity and was probably a determinant factor for its marked selectivity against other related kinases. After an extensive SAR exercise, several compounds from this series were identified as very potent p38## inhibitors. In vivo efficacy of some derivatives was demonstrated to reduce TNF## levels in an acute murine model of inflammation (ED(50) = 0.5 mg/kg in LPS-induced TNF## production when dosed orally 1.5 h prior to LPS administration). The oral efficacy was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally (ED(50) < 1 mg/kg).
(PMID: 21999461)
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 30034
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 30034
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
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