Recent advances in the design and synthesis of heterocycles as anti-tubercular agents

Due to the unusual structure and chemical composition of the mycobacterial cell wall, effective tuberculosis (TB) treatment is difficult, making many antibiotics ineffective and hindering the entry of drugs. With approximately 33% of infection, TB is still the second most deadly infectious disease worldwide. The reasons for this are drug-resistant TB (multidrug resistant and extensively drug resistant), persistent infection (latent TB) and synergism of TB with HIV; furthermore no new chemical entity has emerged in last 40 years. New data available from the recently sequenced genome of the mycobacterium and the application of methods of modern drug design promise much for the fight against this disease. In this review, we present an introduction to TB, followed by an overview of new heterocyclic anti-tubercular moieties published during the last decade. </jats:p

Design, synthesis and evaluation of novel polypharmacological antichlamydial agents

AbstractDiscovery of new polypharmacological antibacterial agents with multiple modes of actions can be an alternative to combination therapy and also a possibility to slow development of antibiotic resistance. In support to this hypothesis, we synthesized 16 compounds by combining the pharmacophores of Chlamydia trachomatis inhibitors and inhibitors of type III secretion (T3S) in gram-negative bacteria. In this study we have developed salicylidene acylhydrazide sulfonamides (11c & 11d) as new antichlamydial agents that also inhibit T3S in Yersinia pseudotuberculosis

N-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors

Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4g, with an IC50 of 2.6 µM as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-N-(3-(oxazolo[4,5-b]pyridin-2-yl)phenyl)acetamide, 4i, with an IC50 of 0.35 µM

<i>N</i>-aryl 2-aryloxyacetamides as a new class of fatty acid amide hydrolase (FAAH) inhibitors

<p>Fatty acid amide hydrolase (FAAH) is a promising target for the development of drugs to treat neurological diseases. In search of new FAAH inhibitors, we identified 2-(4-cyclohexylphenoxy)-<i>N</i>-(3-(oxazolo[4,5-<i>b</i>]pyridin-2-yl)phenyl)acetamide, <b>4g</b>, with an IC₅₀ of 2.6 µM as a chemical starting point for the development of potent FAAH inhibitors. Preliminary hit-to-lead optimisation resulted in 2-(4-phenylphenoxy)-<i>N</i>-(3-(oxazolo[4,5-<i>b</i>]pyridin-2-yl)phenyl)acetamide, <b>4i</b>, with an IC₅₀ of 0.35 µM.</p