Exception That Proves the Rule: Investigation of Privileged Stereochemistry in Designing Dopamine D₃R Bitopic Agonists.

ABSTRACT: In this study, starting from our selective D₃R agonist FOB02-04A (5), we investigated the chemical space around the linker portion of the molecule via insertion of a hydroxyl substituent and ring-expansion of the trans-cyclopropyl moiety into a trans-cyclohexyl scaffold. Moreover, to further elucidate the importance of the primary pharmacophore stereochemistry in the design of bitopic ligands, we investigated the chiral requirements of (+)-PD128907 ((+)-(4a R ,10b R )-2)) by synthesizing and resolving bitopic analogues in all the cis and trans combinations of its 9-methoxy-3,4,4a,10b-tetrahydro-2H,5H-chromeno[4,3-b][1,4] oxazine scaffold. Despite the lack of success in obtain

SUBMITTER: Battiti FO 

PROVIDER: S-EPMC7549273 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature