10.1021/jo960192+.s002
Reza Fathi
Reza
Fathi
M. Jonathan Rudolph
M. Jonathan
Rudolph
Robert G. Gentles
Robert G.
Gentles
Rina Patel
Rina
Patel
Eric W. MacMillan
Eric W.
MacMillan
Michael S. Reitman
Michael S.
Reitman
David Pelham
David
Pelham
Alan F. Cook
Alan F.
Cook
Synthesis and Properties of Combinatorial Libraries of
Phosphoramidates
American Chemical Society
1996
diversity elements
combinatorial libraries
drug discovery program
nonradioactive labels
chemical properties
unfunctionalized diols
monomeric units
Combinatorial Libraries
32 phosphorus
phosphoramidate derivatives
1996-08-09 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Properties_of_Combinatorial_Libraries_of_Phosphoramidates/3702240
We have assembled a set of combinatorial libraries of
phosphoramidates for pharmacological
evaluation. A range of functionalized and unfunctionalized diols,
representing a variety of diversity
elements, were converted into their corresponding dimethoxytrityl
H-phosphonate derivatives which
were coupled to each other to produce H-phosphonate dimers and trimers.
The H-phosphonate
diesters were converted into phosphoramidates by reaction with a wide
range of primary and
secondary amines. Very large libraries (theoretically, in excess
of one million compounds) possessing
five sites of diversity were generated for use in our drug discovery
program. Smaller libraries
with lower molecular weights were also prepared in which only two
monomeric units were coupled
together and converted into their phosphoramidate derivatives.
Methods for the attachment of
both radioactive and nonradioactive labels, including
<sup>32</sup>phosphorus, tritium, and fluorescein,
have
been developed. Representative single sequences were also prepared
and their chemical properties
studied.