By use of parallel chemistry coupled with physicochemical property design, a series of selective ## opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro ## antagonism were confirmed in the tail-flick analgesia model. This model was used to build an more ..
Target
BioActive Compounds: 28
Description:
Title: Design and discovery of a selective small molecule ## opioid antagonist (2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242).
Abstract: By use of parallel chemistry coupled with physicochemical property design, a series of selective ## opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro ## antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the ## K(i) and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers.
(PMID: 21744827)
Abstract: By use of parallel chemistry coupled with physicochemical property design, a series of selective ## opioid antagonists have been discovered. The parallel chemistry strategy utilized key monomer building blocks to rapidly expand the desired SAR space. The potency and selectivity of the in vitro ## antagonism were confirmed in the tail-flick analgesia model. This model was used to build an exposure-response relationship between the ## K(i) and the free brain drug levels. This strategy identified 2-methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine, PF-4455242, which entered phase 1 clinical testing and has demonstrated target engagement in healthy volunteers.
(PMID: 21744827)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment
ChEMBL Assay Type: Binding
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 129
ChEMBL target type: Target is a single protein chain
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Target ID: 129
ChEMBL target type: Target is a single protein chain
Result Definitions
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| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | Ki* | Ki PubChem standard value |  | Float | μM | |
| 2 | BEI | Binding Efficiency Index(nM) | | Float | ||
| 3 | SEI | Surface Efficiency Index(nM) | | Float | ||
| 4 | Ki activity comment | Ki activity comment | String | |||
| 5 | Ki standard flag | Ki standard flag | | Integer | ||
| 6 | Ki qualifier | Ki qualifier | String | |||
| 7 | Ki published value | Ki published value | | Float | nM | |
| 8 | Ki standard value | Ki standard value | | Float | nM | |
| 9 | Ki binding domains | Ki binding domains | String |
* Activity Concentration.
Data Table (Concise)
Classification
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