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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.
NEW Optimer®
Building Blocks
Click below to download a PDF of our NEW
Optimer® building blocks.
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to read the files below. Get
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Optimer®
Building Block Catalog
Click below to download a PDF of our Optimer®
building blocks, sorted by structural
motif and functional group. To download
the entire Optimer® building block
Catalog, click here
(Adobe Acrobat Reader 4 or above is needed
to read the files below. Get
Acrobat Reader Here
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. These
are defined as primary building blocks
and are designated in the catalog with
a . An early example of the use of primary
building blocks used in a lead generation
library was published by Chiron.2 Chiron
used a series of representative amines
in a N-substituted glycine peptoid library
and identified nanomolar hits against
7-transmembrane G-protein-coupled receptors.
We have expanded the primary Optimer®
building blocks to provide sets of secondary
building blocks designed for efficient
SAR exploration in lead optimization,
including some Optimer® building blocks
suitable for Topliss analysis.3 Optimer®
building blocks are available on an individual
compound basis, or in Optimer® Kits organized around a reactive functional
group.
Advantages of
Optimer® Building Blocks:
Efficient
lead optimization
To facilitate the process of probing
structure-activity relationships, Optimer®
building blocks are offered in sets to
expedite synthesis and analysis, including
some Optimer® building blocks that
are also highly suited for Topliss analysis.3
Higher quality
leads
Derived from retrosynthetic analysis
of drugs on the market and in clinical
trials, Optimer® building blocks possess
key drug-relevant characteristics that
address potency, selectivity, physiochemical
properties, drug metabolism and toxicity.
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.
Available
in Optimer® Kits
Optimer® building blocks are available
in pre-defined kits containing 100 mg
of each Optimer® organized around
a reactive functional group to allow rapid
incorporation into your leads.
References:
1. J. Med. Chem. 2000, 43, 3443-3447.
2. J. Med. Chem. 1994, 37, 2678-2685.
3. J. Med. Chem. 1977, 20, 463-469.
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