title: Synthesis of hydantoins and thiohydantoins spiro-fused to pyrrolidines: druglike molecules based on the 2-arylethyl amine scaffold.
abstract: The synthesis of a 144-compound library of hydantoins and thiohydantoins spiro-fused to pyrrolidines is described. These compounds are synthesized from beta-aryl pyrrolidines, providing products with the 2-arylethyl amine moiety, a structural feature often encountered in compounds active in the central nervous system. All possible stereoisomers of the two-stereocenter products are synthesized. The 80-membered hydantoin sublibrary was obtained with yields ranging from 58 to 100% (87% average) and purities from 51 to 100% (87% average) and the 64-membered thiohydantoin sublibrary was obtained with yields ranging from 65 to 100% (89% average) and purities from 67 to 100% (93% 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; D020650:Combinatorial Chemistry Techniques; D006827:Hydantoins / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013867:Thiohydantoins / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000588:Amines; D006827:Hydantoins; D011759:Pyrrolidines; D013141:Spiro Compounds; D013867:Thiohydantoins