Improved loading and cleavage methods for solid-phase synthesis using chlorotrityl resins: synthesis and testing of a library of 144 discrete chemicals as potential farnesyltransferase inhibitors.
The use of chlorotrityl resins for the immobilization of amines is sometimes deterred by the lengthy process of loading the reactants on the resins and product decomposition caused by the reactive chlorotrityl group in the presence of 1% TFA as a cleavage agent. Here, we report improved methods developed for selective and efficient loading of aminobenzoic acid derivatives on chlorotrityl resins and for cleavage of aniline-containing products from the resins without decomposition. These methods led to the synthesis of a library of 144 discrete chemicals as potential farnesyltransferase inhibitors (FTIs) using IRORI's radio-frequency-encoded sorting technique and to the study of the applicability of the bivalence approach to the development of FTIs.
Park
Jewn Giew
JG
Computer-Aided Molecular Design Laboratory, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.
Langenwalter
Kevin J
KJ
Weinbaum
Carolyn A
CA
Casey
Patrick J
PJ
Pang
Yuan-Ping
YP
D000596:Amino Acids; D020650:Combinatorial Chemistry Techniques; D004791:Enzyme Inhibitors; D051231:Farnesyltranstransferase; D015394:Molecular Structure; D012116:Resins, Plant; D060327:Solid-Phase Synthesis Techniques
D000596:Amino Acids; D004791:Enzyme Inhibitors; D012116:Resins, Plant; D051231:Farnesyltranstransferase