Exploring S1 plasticity and probing S1' subsite of mammalian aminopeptidase N/CD13 with highly potent and selective aminobenzosuberone inhibitors.

In order to probe the S1 and S1' mammalian aminopeptidase N subsites, racemic 1- or 4-substituted 7-aminobenzocyclohepten-6-one derivatives were synthesized and evaluated for their ability to inhibit mammalian aminopeptidase N. We focused on improving the physicochemical and ADME properties of this series by targeting lipophilicity and LELP score. Some 4-heteroaryl substituted analogues displayed reduced lipophilicity and enhanced inhibition potency with Ki values in the nanomolar range.

A novel amino-benzosuberone derivative is a picomolar inhibitor of mammalian aminopeptidase N/CD13.

A new class of low molecular weight, highly potent and selective non peptidic inhibitors of aminopeptidase N (APN/CD13) is described. We report the synthesis and in vitro evaluation of racemic substituted analogues of 7-amino-benzocyclohepten-6-one 1a. We investigated various substitutions on the aromatic ring with phenyl and halogen groups.

Synthesis and biological evaluation of novel benzodioxinocarbazoles (BDCZs) as potential anticancer agents.

We report the efficient synthesis and biological evaluation of new benzodioxinoindolocarbazoles heterocycles (BDCZs) designed as potential anticancer agents. Indolic substitution and maleimide variations were performed to design a new library of BDCZs and their cytotoxicity were evaluated on two representative cancer cell lines. Several derivatives have shown a marked cytotoxicity with IC(50) values in the nanomolar range.

Quantitative structure-retention and retention-activity relationships of some 1,3-oxazolidine systems by RP-HPTLC and PCA.

A quantitative structure-retention and retention-activity relationships investigations were performed on the lipophilicities of some 1,3-oxazolidine systems as estimated by RP-HPTLC retention parameters. The classical R(Mo) values were compared with the factors scores obtained by principal component analysis based also onto the TLC retention data. The lipophilicities (R(Mo) and factor scores) were correlated with the theoretical molecular descriptors of 1,3-oxazolidine derivatives providing by the ALCHEMY 2000 software package.