Cyclic urea diol

Additional modeling studies, together with synthetic considerations, led to the design of the cyclic urea diol framework (27). Molecular modeling of this... 

HIV-1 protease (HIV-1 PR) Non-peptide, C2-symmetric cyclic urea derivatives were designed de novo to fit the HlV-i PR active site. These novel, conformationally-constrained inhibitors feature a diol functionality that interacts with the catalytic aspartates while an urea oxygen mimics a structural water mediating substrate interactions with the enzyme flap. The required absolute configuration at four chiral centers was correctly predicted. Potent, bioavailable clinical candidates emerged from this work. i37 ... 

RT and HIV PR is capable of reducing the viral load in blood patients. These enzymes, which exist respectively as a heterodimer and a homodimer for HIV RT and HTV PR, are well-characterized more than 170 structures of HIV PR and its complexes with various inhibitors have been solved by protein crystallography techniques. Thus, a dipalmitoylated derivative of 2,7-naphthalene disulfonic acid demonstrated micromolar activity for both fflV-1 and HIV-2 RT (Fig. 16.14). Symmetrical nature of HTV PR was used in the search for novel anti-HTV drugs that would embody the predicted characteristic of the active site. The design of inhibitors of HIV PR has led to symmetrical compounds, which can be divided into two groups (1) pseudosymmetrical compounds, like derivatives A 74704 ° and L 700,417 which contain asymmetric atoms in close proximity to the inhibitor two-fold axis (2) fully Ca-symmetrical inhibitors like the cyclic urea and the diol derivatives (Fig. 16.14). 

Diamines, 1,2-diols, or 1,2-amino alcohols react with (1) to form cyclic ureas,carbonates, or oxazolidinones, respectively. In the case of cyclohexane-1,2-diols, the c/s-diol reacts much more rapidly than the trans, as would be expected. Thia-zolidinones can also be prepared using (1). ... 

Cyclic carbonates can also be obtained in the reaction of diols and urea, an activated form of C02 (Scheme 6.10).79 The ammonia produced in the reaction can be recycled via the Bosch-Meiser process. 

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