New Lipophilic Hydroxamates as Promising Trypanocidal Agents: Design, Synthesis, SAR, and Conformational Behavior Studies.

A series of novel hydroxamic acid derivatives was designed and synthesized, and their growth inhibitory activity against bloodstream form was evaluated. These compounds are based on conformationally constrained, lipophilic, spiro carbocyclic 2,6-diketopiperazine (2,6-DKP) scaffolds and bear a side pharmacophoric functionality that contains an acetohydroxamic acid moiety (CHCONHOH) linked with the imidic nitrogen atom of the 2,6-DKP ring via an acetamido portion [CHCON(R), R = H, CH]. Most of these analogues were active in the midnanomolar to low micromolar range against .

Mapping the Melatonin Receptor. 8. Selective MT2 Agonists Derived from 5,6-Dihydroindolo[2,1-a]isoquinolines and Related Systems.

A series of substituted indolo[2,1-a]isoquinolines and indolo[1,2-a]benzoxazines have been prepared, as melatonin analogues, to investigate the nature of the binding site of the melatonin receptor. Agonist and antagonist potency of all the analogues was measured using the [35S]GTPγS binding assay protocol. The binding affinity of the analogues were measured by competition binding studies against the human MT1 (hMT1) and MT2 (hMT2) receptors stably transfected in Chinese Hamster Ovarian (CHO) cells, using 2-[ I]-iodomelatonin, as a ligand.

Synthesis and evaluation of novel 2,4-disubstituted arylthiazoles against .

The design, synthesis and pharmacological evaluation of the 4-substituted-2-[3-(adamant-1-yl)-4-fluorophenyl]thiazoles , the 4-substituted-2-[4-(adamant-1-yl)phenyl]thiazoles , the 2-substituted-4-[4-(adamant-1-yl)phenyl]thiazoles , the -substituted 2-phenylthiazol-4-ethylamides , and the -substituted 4-phenylthiazol-2-ethylamides , is described. Compounds and exhibit trypanocidal activity in the range of IC = 0.42 μM and IC = 0.

Development and Characterization of Eudragit-Based Electrospun Nanofibrous Mats and Their Formulation into Nanofiber Tablets for the Modified Release of Furosemide.

Furosemide, a chloride channel blocker ordinarily used as a high-ceiling or loop diuretic, is practically insoluble in water and dilute acids. Due to its acidic nature, furosemide is mostly absorbed in the stomach and in the upper small intestine. Efforts have focused on the development of sustained release systems of furosemide in order to improve the effectiveness of the drug, which exhibits poor aqueous solubility and poor permeability.

Fluorine substituted methoxyphenylalkyl amides as potent melatonin receptor agonists.

A series of fluorine substituted methoxyphenylalkyl amides were prepared with different orientations of the fluorine and methoxy groups with respect to the alkylamide side chain and with alkyl sides of differing lengths ( = 1-3). β-Dimethyl and α-methyl derivatives were also synthesised. The compounds were tested as melatonin agonists and antagonists using the pigment aggregation of melanophores as the biological assay.