“…increased lipophilicity leads to increased cytotoxicity). A similar correlation ( r 2 = 0.703; n = 174) between log CC 50 and log k ‘ is observed for several additional series of aminodiol inhibitors (Figure ; the 174 aminodiol analogs in this broad study incorporate a very wide variety of structural features encompassing hydroxylated carbamates,4b α-hydroxy amide,22a and α-amino amide 22b,c compounds extended to the S 2 and S 3 subsites). 2 log k ‘ vs log CC 50 of P 1 ‘ aminodiol analogs. 3 log k ‘ vs log CC 50 of all classes of aminodiols.…”
A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1' were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1' phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (10l, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.
“…increased lipophilicity leads to increased cytotoxicity). A similar correlation ( r 2 = 0.703; n = 174) between log CC 50 and log k ‘ is observed for several additional series of aminodiol inhibitors (Figure ; the 174 aminodiol analogs in this broad study incorporate a very wide variety of structural features encompassing hydroxylated carbamates,4b α-hydroxy amide,22a and α-amino amide 22b,c compounds extended to the S 2 and S 3 subsites). 2 log k ‘ vs log CC 50 of P 1 ‘ aminodiol analogs. 3 log k ‘ vs log CC 50 of all classes of aminodiols.…”
A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1' were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1' phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (10l, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.
“…Optically active 2-hydroxyamide derivatives are frequently utilized as chiral building blocks not only for synthesizing biologically active compounds [ 1 , 2 , 3 , 4 ], but also for preparing asymmetric catalysts and chiral auxiliaries [ 5 , 6 ]. Consequently, considerable effort has been devoted toward developing efficient methods for synthesizing these compounds, including enzymatic [ 7 ] and chemical transformations [ 8 , 9 , 10 ].…”
Various optically active 2-hydroxyamide derivatives are produced based on the kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst, via asymmetric esterification and acylation. It was revealed that a tertiary amide can be used with this novel protocol to achieve high selectivity (22 examples; s-value reaching over 250). The resulting chiral compounds could be transformed into other useful structures while maintaining their chirality.
“…For example, a-hydroxyamides have been identified as inhibitors of methionine aminopeptidase-2 and as HIV protease inhibitors [7,8]. Mycalamides are a class of a-hydroxyamides that exhibit potent antitumor activity [9].…”
A simple and efficient approach for the synthesis of a-hydroxyamides in fairly good yields by the reaction of aromatic aldehydes and alkyl isocyanides at room temperature is presented.
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