Cyclopentane scaffold

Further SAR studies on the cyclopentane scaffold have included variation of the hydrophobic side-chain to incorporate a carboxamide substituent (Chand et al. 2004), equivalent to the C6-carboxamide derivatives of zanamivir, and extension of the length of the hydrophobic side-chains (Chand et al. 2005a). Analogues that incorporate a longer 4-heptyl side-chain showed comparable efficacy to 34 upon oral and intranasal administration in mice, and comparable or better efficacy than oseltamivir and zanamivir (Chand et al. 2005a). 

A Sialidase Inhibitor Based on a Cyclopentane Scaffold The Development of Peramivir... 

Even more extensive optimization of reaction conditions was performed in the group of Aggarwal [10]. With the aim to synthesize prostaglandins, their primary goal was to obtain the intermediate bicyclic lactol 30, which allows stereoselective conjugate addition of organocuprates and derivatization of the cyclopentane scaffold. For the synthesis of the bicyclic intermediate, the researchers envisioned an asymmetric aldol dimerization of succinaldehyde (23) by means of a proline-based... 

Patkl994 Patek, M., Drake, B. and Lebl, M., All-Cis Cyclopentane Scaffolding for Combinatorial Solid Phase Synthesis of Small Non-Peptide Compounds, Tetrahedron Lett., 35 (1994) 9169-9172. 

A number of researchers have reported and demonstrated that maintaining the appropriate position of the substituents on a cyclic scaffold to interact with the established conserved amino acid residues involved in substrate binding can lead to development of new classes of influenza virus sialidase inhibitors [117]. Two drugs based on five-membered ring scaffolds have been developed as potent sialidase inhibitors. Cyclopentane derivative 24 (BCX-1812, peramivir) [117, 118] and pyrrolidine derivative 25 (ABT-675) [119] show nanomolar levels of inhibition of both influenza A and B viral sialidases (Fig. 17.13). 

The synthesis of carbocycles via a two-component cascade reaction in an asymmetric fashion has attracted much attention from the chemical community. Due to his importance in natural products, the synthesis of cyclopropanes, cyclopentanes, and cyclohexanes has been one of the common goals for organocatalytic methodologies. The high stereoselectivity achieved, green procedures, and soft conditions make this organocatalytic approximation one of the most attractive ones to build complex cyclic scaffolds. 

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