The synthesis and biological evaluation of 2-amino-4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes as allosteric modulators of the A1 adenosine receptor |
| |
| Authors: | Aurelio Luigi Christopoulos Arthur Flynn Bernard L Scammells Peter J Sexton Patrick M Valant Celine |
| |
| Affiliation: | a Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia
b Drug Discovery Biology Laboratory, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, 381 Royal Parade, Parkville, Vic. 3052, Australia |
| |
| Abstract: | A series of 2-amino-4,5,6,7,8,9-hexahydrocycloocta[b]thiophenes were prepared and evaluated as potential allosteric modulators of the A1 adenosine receptor (AR). The structure-activity relationships of the 3-position were explored along with varying the size of the cycloalkyl ring. 2-Aminothiophenes with amide and hydrazide groups in the 3-position were completely inactive in an A1-AR-mediated ERK1/2 phosphorylation assay, yet most of the 3-benzoyl substituted compounds exhibited allosteric effects on responses mediated by the orthosteric agonist, R-PIA. Despite finding an increase in both agonistic and allosteric activities by going from a cyclopentyl ring to a cyclohexyl ring in the 3-benzoyl series, decreases were observed when further increasing the ring size. Varying the substituents on the phenyl ring of the 3-benzoyl group also affected the activity of these compounds. |
| |
| Keywords: | Allosteric modulator A1 adenosine receptor (A1-AR) 2-Amino-3-benzoylthiophene G protein-coupled receptors (GPCRs) |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
