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Array BioPharma has created a series of
drug-relevant Optimer® building blocks
which are specifically designed for generating
pharmaceutically-relevant leads and for
the rapid exploration of structure-activity
relationships (SAR) surrounding those
leads.
How are
Optimer® Building Blocks created?
Using our proprietary software program,
RADICAL, we have created a retrosynthetic
analysis of small molecule compounds that
have entered into human clinical trials.
This analysis, combined with the intuition
of our medicinal chemists, is used to
identify key synthetic fragments or structural
motifs common to compounds under clinical
investigation or current drugs on the
market.
Privileged
Molecules
Recurring fragments or structural motifs
are often referred to as “privileged”
structures for their affinity to bind
to pharmaceutically relevant targets.
For example, seventy percent of all drugs
from the World Drug Index (Derwent) contain
the aromatic structural motif. More specifically,
biphenyl and benzhydryl moieties are common
in current drugs and, as such, these structural
motifs are broadly represented in this
catalog. Our approach to identifying these
privileged structural motifs was recently
validated by experimental evidence that
supports the tendency for biphenyl and
benzhydryl motifs to bind to proteins
of biological interest.1 The Optimer®
building block catalog offers numerous
additional drug-relevant structural motifs.
The biological importance and utility
of each structural motif is described
in the catalog.
Optimer® building blocks are privileged
structural motifs with various reactive
functional groups including aldehydes,
carboxylic acids, amines and sulfonyl
chlorides for incorporation into various
scaffolds. Unsubstituted structural motifs
are used in lead generation providing
important information that can be used
to define SAR studies around a hit.
Advantages of
Optimer® Building Blocks:
Synthesis
ready
Ideally-suited for combinatorial or
parallel synthesis, Optimer® building
blocks contain a variety of reactive functional
groups, including orthogonally-protected
functional groups, for facile incorporation
into various scaffolds. Array’s
primary Optimer® building blocks can
be incorporated into lead generation libraries.
Leads can be optimized with a series of
SAR-derived secondary Optimer® building
blocks in lead explosion libraries or
via traditional medicinal chemistry techniques.
References:
1. J. Med. Chem. 2000, 43, 3443-3447.
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