title: Convergent synthesis of complex diketopiperazines derived from pipecolic acid scaffolds and parallel screening against GPCR targets.
abstract: A convergent approach to highly functionalized diketopiperazines (DKPs) using enantioenriched pipecolic acids is described. Scandium triflate-catalyzed [4 + 2] aza-annulation was employed to produce stereochemically well-defined building blocks. A resin "catch and release" strategy was devised to convert annulation products to pipecolic acid monomers. Complex diketopiperazines were efficiently assembled utilizing one-pot cyclodimerization of pipecolic acids. Massively parallel screening of the complex DKPs against a panel of molecular targets identified novel ligands for a number of G-protein-coupled receptors (GPCRs).
authors.affiliation: Department of Chemistry and Center for Chemical Methodology and Library Development (CMLD-BU), Boston University, 590 Commonwealth Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Sivaraman
authors.initials: S
authors.lastname: Dandapani
authors.forename: Ping
authors.initials: P
authors.lastname: Lan
authors.forename: Aaron B
authors.initials: AB
authors.lastname: Beeler
authors.forename: Scott
authors.initials: S
authors.lastname: Beischel
authors.forename: Athier
authors.initials: A
authors.lastname: Abbas
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: John A
authors.initials: JA
authors.lastname: Porco
authors.forename: James S
authors.initials: JS
authors.lastname: Panek
mesh_terms: D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D018360:Crystallography, X-Ray; D054659:Diketopiperazines; D004353:Drug Evaluation, Preclinical; D008958:Models, Molecular; D008968:Molecular Conformation; D010875:Pipecolic Acids / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D001372:Aza Compounds; D054659:Diketopiperazines; D010875:Pipecolic Acids; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; C031345:pipecolic acid