Solid-phase/solution-phase combinatorial synthesis of neuroimmunophilin ligands.
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.
Rabinowitz
M
M
Glaxo Wellcome, Inc., Research Triangle Park, NC 27709, USA. mhr20812@glaxowellcome.com
Seneci
P
P
Rossi
T
T
Dal Cin
M
M
Deal
M
M
Terstappen
G
G
D020650:Combinatorial Chemistry Techniques; D020104:Immunophilins / Q000378:metabolism*; D008024:Ligands; D011759:Pyrrolidines / Q000737:chemistry / Q000378:metabolism; D022021:Tacrolimus Binding Proteins
C104949:GPI 1046; D008024:Ligands; D011759:Pyrrolidines; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins