| Text Search: | |
| Enter catalog number, CASRN, name, or partial name. | |
CLICK FOR STRUCTURE SEARCH
About
About Our Staff
August, 2011: Barry Feigelman was recently hired as our new North American and International Account Manager. He has worked over the last eleven years as an account manager within the pre-clinical drug discovery chemistry sector. He spent six years with ComGenex, Intl, becoming familiar with the needs of medicinal chemists and other drug discovery scientists for small molecule compound libraries, custom chemistry services and chemistry instrumentation. Over the last 5 years, he has represented a European based drug discovery chemistry company, InFarmatik, Inc. in a similar capacity. Barry, who joined Focus Synthesis in August 2011, looks forward to providing you with the superior customer service that Focus Synthesis customers have become accustomed to.
Biotargets and Precursors for Biotarget Ligands
Focus Synthesis carries numerous building blocks that have been used as precursors for enzyme inhibitors,
receptor blockers, receptor agonists, and other small molecule ligands that bind to pharmaceutically relevant
macromolecular targets. Most of these ligands are drug candidates developed in discovery programs. The
macromolecular targets, precursor structures, and literature or patent references are listed below. You can
see pricing and availability information for the Focus Synthesis precursors by clicking on the title or chemical
structure. Clicking on the reference will lead to the abstract or entire publication if available.
Click here to download a .pdf with inhibitor, antagonist, and agonist precursors from Focus Synthesis For 26 Biotargets.
Knowledge-Enabling Building Blocks
Focus Synthesis is a new research chemical supplier that uses rational principles based in chemoinformatics in the design
of chemical building blocks that are ideally suited for DOS (diversity-oriented synthesis). Focus Synthesis products include
members of unique and underrepresented substructure classes, building blocks designed for thorough chemical space coverage,
exotic heterocycles and precursors for highly focused combinatorial libraries. If you purchase rare chemicals from Focus
Synthesis, you will have a time-saving tool set for discovering the drugs of the future by exploring uncharted chemical
space, expanding SAR knowledge, and bolstering your IP position.
Focus Synthesis offers synthons, building blocks, and research chemicals that are optimized for drug discovery using
cheminformatics-based design. In addition to being a research chemical supplier specializing in drug candidate intermediates
and other organic chemicals, Focus Synthesis also provides custom synthesis outsourcing, in-house custom chemistry, and
proprietary design services.
Overview of Rare and Unique Substructure® Classes
Many of the building blocks in the Focus Synthesis catalog belong to substructure classes that are rare or unavailable in other chemical catalogs. For these molecules, a substructure search in the Available Chemicals Directory (Symyx software) will yield 0 or 1 structure. The underrepresented substructures in these synthons make them ideal for the development of non-obvious variations on current lead molecules, thereby strengthening intellectual property positions. In addition, these distinctive building blocks are excellent tools for improving diversity and chemical space coverage. Click here to see an online subcatalog of building blocks with rare and unique substructures®. Our Rare and Unique Subcatalog listing is updated every 6 months, removing products that are no longer rare. The last update was made in July 2009.
Overview of Leadlike "Rule of Three" Synthons for FBLD/FBDD
Recently, a set of rules has been developed to help identify small molecules suited for the fragment-based lead discovery
(FBLD), also known as fragment-based drug discovery (FBDD). This novel approach to drug discovery involves screening
libraries of low-molecular weight fragments for their ability to interact with a macromolecular target through protein
x-ray crystallography, NMR, and other techniques. Congreve, Carr, Murray and Jhoti determined that small molecules that
obey the "Rule of Three" are most suited to this approach: FW < 300, hydrogen bond donors <=3, hydrogen bond
acceptors <=3, ClogP <=3. The "RubyRO3" building blocks meet the basic Rule of Three criteria, contain at least one
functional group and are also Rare and Unique Substructures®. More than 80% of these are predicted to be
stable in physiological buffers, and could be used directly as screening compounds particularly suited for fragment-based
lead discovery. All of the "Rule of Three" products are particularly well suited as precursors for lead-like and drug-like
molecules.
Click
here to view structures, prices and availability for "Rule of Three" building blocks.
References for "Rule of Three":
M. Congreve, R. Carr, C. Murray and H. Jhoti, Drug Discovery Today V8 pp 876-877 (2003)
The Rarest of the Rare
Focus Synthesis has also developed subsets of the Rare and Unique Substructure® Classes that are even more
distinctive and unusual.
RubyScaffoldsTM are exotic heterocycles in which the unsubstituted heterocycle
is found in fewer than 1 in 10,000 (<0.01%) of the molecules in emolecules.com when a substructure search. These
distinctive heterocycles can help you to explore new areas of chemical structure space. They can also help to enhance your
IP position because few if any derivatives are commercially available and most test molecules that you make from them will
be patentable. Click here
to see an online catalog of RubyScaffoldTM exotic heterocycles. Examples of 4 RubyScaffoldsTM
currently in stock are shown here, with the rare heterocyclic substructure highlighted red:
For RubyShapesTM, the substructure is rare or unique in commercial catalogs for all possible heavy atom substitutions. The substructure is a graph consisting of "wild card" atoms and bonds, and yields at most 1 structure when used in a substructure search in the Available Chemicals Directory (Symyx software). As building blocks, RubyShapesTM are ideal for improving the diversity of molecular shapes in your corporate collection. The following figure depicts 4 RubyShapesTM molecular structures from the Focus catalog, alongside their rare substructure shapes (substructures highlighted in green):
RubySynthonsTM are ultra-rare molecules containing substructures that are not found in the very large Emolecules database (>10 million organic structures from the literature as well as commercial sources). RubySynthonsTM are ideal as starting points for improving the overall diversity of your corporate compound collections and for helping you create highly novel, patentable leads. Examples of RubySynthonsTM are shown below, with rare substructures highlighted in blue:
Overview of Cheminformatic Gap Fillers
Focus Synthesis has introduced Cheminformatic Gap Fillers in order to provide druggable
building blocks that significantly improve the diversity of commercially available building blocks. One approach to
measuring chemical diversity involves determining how evenly distributed a set of molecules are in chemical property space,
where the dimensions of the space can be physical properties, chemical properties, topological or geometric parameters
based on structure, etc. Useful descriptors for this type of cheminformatic analysis include chemical properties, physical
properties, and structure based parameters, and various combinations thereof that can be independently increased or
decreased in a straightforward, intuitive manner using structural changes. Polar Surface Area (FISA, area in angstroms of
O and N atoms) and Weakly Polar Surface Area (WPSA, area in angstroms of F, Cl, Br, I, S, and P) were chosen here because
of their relationship to drug bioavailability in mammals (Wessel et al, 1998; Votano et al, 2004).
In the example given here, the parameters were determined using QikProp software from Schrodinger. In the scatter plot shown in the
example below, many gaps are evident in the distribution of commercial bromopyridines (ACD) because many of these compounds
share similar properties and cluster together. The Focus Gap Fillers have been designed to occupy the gaps, so that their
FISA and WPSA values differ by at least 10 angstom squared units from any bromopyridine available from another vendor.
Inclusion of Focus Gap Filler building blocks will therefore significantly enhance the diversity of combinatorial libraries
derived from bromoarenes. Click here
to view structures, prices and availability for Cheminformatic Gap Filler building blocks.
References for cheminformatic gap fillers:
ACD: abbreviation for Available Chemicals Directory (a product of MDL Information Systems).
Wessel MD, Jurs PC, Tolan JW, Muskal SM,
J Chem Inf Comput Sci. 1998 V38(4): pp726-35
Votano JR, Parham M, Hall LH, Kier LB.
Mol Divers. 2004 V8: pp379-91
Synthetic Chemistry Using Focus Synthesis Building Blocks
Many of the synthons and building blocks offered by Focus Synthesis are so unusual that their synthetic chemistry as
precursors is not common knowledge. Beginning with isothiazole (FS000701), this section will briefly review synthetic
chemistry using a chemical structure schematic with literature references. Where applicable, biological activity will be
tabulated for selected end-products formed from Focus Synthesis precursors. These schematics are not meant to be at all
comprehensive, but will provide a representative sample of the organic and medicinal chemistry publications for products
formed from Focus Synthesis building blocks.
The chemistry of isothiazole (FS000701) is reviewed in the schematic below.
Click here
to see current pricing and availability for isothiazole.
The chemistry of 7-Bromo-benzo[b]thiophene (FS001166) is reviewed below. Click here to see current pricing and availability for 7-Bromo-benzo[b]thiophene.
Overview of Atom Scanning Tools for Highly Focused Libraries
Focus Synthesis offers sets of isomeric building blocks that differ from one another in the placement of a single methyl group or fluorine atom. For example, the following are currently included in the catalog as Special Order compounds useful as precursors for a methyl scan sublibrary:
Pharmaceutical lead sets made from these building blocks can be used to carry out a comprehensive "methyl scan",
determining the effects of methyl group placement on biological activity. The methyl scan technique is a very systematic,
rational way of improving the understanding of SAR, while providing a starting point for further modifications to improve
selectivity, ADMET characteristics, and potency.
Selected literature references concerning the use of methyl scans in SAR elucidation and design of bioactive molecules:
Pirrung MC et al.
J. Amer. Chem. Soc. V127 pp 4609-4624 (2005)
Rajeswaran WG, Hocart SJ, Murphy WA, Taylor JE, Coy DH.
J Med Chem. 2001 Apr 26; V44 (9): pp 1416-1421.
Slon-Usakiewicz JJ, Sivaraman J, Li Y, Cygler M, Konishi Y.
Biochemistry. 2000 Mar 7; V39 (9): pp 2384-2391.
Catalogs (Updated December 15, 2011)
| Copyright © 2004 - 2012 Focus Synthesis LLC. |