Design Vertex compounds

There are various types of boron hydride and borohydride ion. Those with a closed polyhedron of boron atoms are designated closo compounds. Ones in which there is an incomplete polyhedron (by removal of one vertex) are called nido compounds (from the Greek word for nest ). Those with a more open structure (removal of two or more vertices) are arachno compounds (from the Greek spider ). 

Noteworthy in this perspective is the work by Bemis and Murcko, who developed a method for decomposing molecules into frameworks, sidechains, and linkers and analyzed the statistical occurrence of the frameworks within a subset of drugs listed in the CMC catalog [112]. This analysis revealed that only 32 frameworks describe the shapes of half the drugs in the CMC set (-5000 compounds) and resulted in the design of the SHAPES NMR screening library-a limited but diverse library of small molecules derived from the shapes most commonly found - which Vertex uses within the lead-finding process [113]. 

Several other approved AIDS drugs that act by inhibition of HIV-P have also been developed through use of SBDD methods. Compound (42) (amprenavir, Agenerase, also known as VX-478) is the most recent addition to the HIV-P inhibitors approved for human antiviral treatment, and differs significantly from earlier inhibitors. Compound (42) was specifically designed by Vertex scientists to minimize molecular weight to increase oral... 

Analysis of the structural information from the X-ray models allowed the design at Vertex of a new scaffold for potent inhibition of MAPK p38a, as shown for compound (84) (VX-745). This design process, SBDD through... 

Although, at the time of discovery FK 506 was reported as a new immunosuppressant agent being 100-fold more potent than cyclosporin A, efforts to displace cyclosporin A by FK 506, commercialized as tacrolimus, failed until today. It is worth mentioning that FK 506 stimulated the setup of the venture capital funded US company Vertex that aims at a designed drug to treat HIV infections starting from FK 506 as a lead compound. 

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