title: Solution-phase parallel annulation of (thio)hydantoins to tetrahydroisoquinolines and tetrahydro-beta-carbolines containing the 2-arylethyl amine scaffold.
abstract: The one-step solution-phase parallel synthesis of two structurally diverse libraries of pharmacologically important compounds is described. The presented compounds combine three privileged structures: the 2-arylethyl amine moiety, a tetrahydro(hetero)areno[c]pyridine, and a (thio)hydantoin. These compounds are synthesized by annulation of a hydantoin or a 2-thiohydantoin ring to tri- or tetracyclic scaffolds, containing the 2-arylethyl amine moiety and a tetrahydroisoquinoline, a tetrahydro-beta-carboline, or a tetrahydrofuro[3,2-c]pyridine. The annulation leads to pharmacologically relevant structural motifs such as imidazopyrroloisoquinolines, dioxoloimidazopyrroloisoquinolines, furoimidazopyrrolopyridines, and imidazopyrrolopyridoindoles. Both libraries were obtained with quantitative yields. The 36-membered hydantoin library was obtained with purities from 57 to 100% (90% average) and the 32-membered thiohydantoin library with purities from 73 to 100% (94% average).
authors.affiliation: Institute for Molecules and Materials, Radboud University Nijmegen, Toernooiveld 1, Nijmegen, The Netherlands.
authors.forename: Daniel
authors.initials: D
authors.lastname: Blanco-Ania
authors.forename: Pedro H H
authors.initials: PH
authors.lastname: Hermkens
authors.forename: Leo A J M
authors.initials: LA
authors.lastname: Sliedregt
authors.forename: Hans W
authors.initials: HW
authors.lastname: Scheeren
authors.forename: Floris P J T
authors.initials: FP
authors.lastname: Rutjes
mesh_terms: D000588:Amines / Q000737:chemistry; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis / Q000737:chemistry; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D013867:Thiohydantoins / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000588:Amines; D002243:Carbolines; D004364:Pharmaceutical Preparations; D044005:Tetrahydroisoquinolines; D013867:Thiohydantoins; C009804:tryptoline