Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented. ..more
Tested Compound:
Description:
Title: Discovery of 4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undec-9-yl}methyl)phenoxy]benzoic acid hydrochloride: a highly potent orally available CCR5 selective antagonist.
Abstract: Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented.
(PMID: 21658961)
Abstract: Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented.
(PMID: 21658961)
Comment
Putative Target:
ChEMBL Target ID: 50588
Target Type: ORGANISM
Pref Name: Canis familiaris
Organism: Canis lupus familiaris
Tax ID: 9615
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
ChEMBL Target ID: 50588
Target Type: ORGANISM
Pref Name: Canis familiaris
Organism: Canis lupus familiaris
Tax ID: 9615
Confidence: Target assigned is non-molecular
Relationship Type: Non-molecular target assigned
Categorized Comment
ChEMBL Assay Type: ADMET
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Assay Test Type: In vivo
ChEMBL Assay Data Source: Scientific Literature
ChEMBL Assay Test Type: In vivo
Result Definitions
| TID | Name | Description | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||
| 1 | T1/2 activity comment | T1/2 activity comment | String | |||
| 2 | T1/2 standard flag | T1/2 standard flag |  | Integer | ||
| 3 | T1/2 qualifier | T1/2 qualifier | String | |||
| 4 | T1/2 published value | T1/2 published value | | Float | hr | |
| 5 | T1/2 standard value | T1/2 standard value | | Float | hr |
Data Table (Concise)
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