Medicinal Chemistry - Volume 4, Issue 1, 2008

The novel 4-phenoxy-1,2,3,4-tetrahydroisoquinolines 6a-c and their rigid congeners 4,5,6,6a- ydrochromeno[ 2,3,4-de]isoquinolines 7a,b were synthesized in order to obtain dopamine D2-like receptor ligands. The new compounds were evaluated for their in vitro binding affinities, in vivo behavioral activities on rats, and for their effects on rat brain neurochemistry. Compounds 6b (toward both D2 and D3 dopamine recept Read More

In order to get insight into the trypanocidal mechanism of action of a series of 5-nitrofuryl containing hiosemicarbazones some studies related to their bioreduction were performed. Electron spin resonance spectra of radicals generated in T. cruzi by compounds' bioreduction were analyzed. Three different patterns of ESR signals were observed for the different assayed compounds. These results were in agreement with the c Read More

Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that plays a critical role in down-regulating insulin signaling through dephosphorylation of the insulin receptor. Inhibitors of PTP1B showed increased insulin sensitivity and normalize plasma glucose level and thus are useful therapeutic agents for the treatment of diabetes. A series of functionalized 4,5-dihydronaphthofurans and dibenzofurans were synthesized, studied t Read More

5-Aminosalicylic acid is one of the drugs most commonly used for inflammatory bowel disease treatment, although its use is limited due to side effects. The aim of this work was to synthesize four 5-ASA derivatives (1-4) and analyze their pharmacological effects. The compound structures were elucidated by spectral (IR and 1H and 13C-NMR) analysis, and their analgesic effects and lethal doses 50 (LD50) were evaluated in Read More

Mathematical models were developed for the estimation of human carbonic anhydrase (CA) II inhibition. A large set of 95 CA inhibitors incorporating diverse aromatic rings were used for this purpose. The numerical descriptors used were distance- and connectivity- based indices, quantum -theoretical descriptors and Balaban and Balaban type descriptors of molecular structure. After descriptor generation, multiple Read More

A series of piperazinephenethylamines were synthesized to study the contribution of a basic amine to binding affinity at the melanocortin-4 receptor. Several potent compounds from this series possessed subnanomolar Ki values in a competition binding assay.

HIV protease inhibitors are the backbone of HIV therapy. In addition to blocking intracellular HIV protease and dramatically decreasing viral burden, the protease inhibitors also regulate apoptosis. A growing body of data has confirmed the immunomodulatory effects of HIV protease inhibitors which block CD4+ and CD8+ T cell death in models of HIV infection. The mechanism of this apoptosis inhibition is still under active invest Read More

A method called “Emerging Chemical Patterns” (ECP) has recently been introduced as a novel approach to binary molecular classification (for example, “active” versus “inactive”). The underlying pattern recognition algorithm was first introduced in computer science and then adopted for applications in medicinal chemistry and compound screening. A special feature is its ability to accurately classify molecules on the basis Read More