title: Solid-phase/solution-phase combinatorial synthesis of neuroimmunophilin ligands.
abstract: A novel solid-phase/solution-phase strategy for the synthesis of neuroimmunophilin ligands based on GPI 1046 was developed. The synthesis employs a solid-phase esterification strategy followed by a solution-phase pyruvic amide formation to produce multi-milligram quantities of discrete compounds for assay. The protocol was applied to a production library of 880 discrete compounds. A highlight of the strategy is an aqueous extractive purification of the final compounds using a novel liquid/ice extraction system developed for high throughput.
authors.affiliation: Glaxo Wellcome, Inc., Research Triangle Park, NC 27709, USA. mhr20812@glaxowellcome.com
authors.forename: M
authors.initials: M
authors.lastname: Rabinowitz
authors.forename: P
authors.initials: P
authors.lastname: Seneci
authors.forename: T
authors.initials: T
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Dal Cin
authors.forename: M
authors.initials: M
authors.lastname: Deal
authors.forename: G
authors.initials: G
authors.lastname: Terstappen
mesh_terms: D020650:Combinatorial Chemistry Techniques; D020104:Immunophilins / Q000378:metabolism*; D008024:Ligands; D011759:Pyrrolidines / Q000737:chemistry / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
chemical_list: C104949:GPI 1046; D008024:Ligands; D011759:Pyrrolidines; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins