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 ..
Tested Compound:
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
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
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
ChEMBL Assay Type: ADMET
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Assay Test Type: In vitro
ChEMBL Assay Tissue: Liver
ChEMBL Assay Subcellular Fraction: Microsomes
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Assay Test Type: In vitro
ChEMBL Assay Tissue: Liver
ChEMBL Assay Subcellular Fraction: Microsomes
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | CL activity comment | CL activity comment | String | |||
| 2 | CL standard flag | CL standard flag |  | Integer | ||
| 3 | CL qualifier | CL qualifier | String | |||
| 4 | CL published value | CL published value | | Float | mL.min-1.kg-1 | |
| 5 | CL standard value | CL standard value | | Float | mL.min-1.kg-1 |
Data Table (Concise)
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