Showing papers in "Bioorganic & Medicinal Chemistry Letters in 2013"

TL;DR: A medicinal chemistry program has led to the discovery of the clinical candidate NVP-BYL719, a binding model rationalizing the high selectivity and potency of a particular series of 2-aminothiazole compounds in inhibiting PI3Kα.

TL;DR: Drug discovery efforts directed towards the liver and transmission stages are in their infancy but are receiving increasing attention as targeting these stages could be instrumental in eradicating malaria.

TL;DR: The optimization of a potent and highly selective series of dual m TORC1 and mTORC2 inhibitors is described, particularly aimed at reducing the rate of metabolism in human hepatocyte incubations, resulted in the discovery of the clinical candidate AZD2014.

TL;DR: Novel dispirooxindole-pyrrolidine derivatives have been synthesized through 1,3-dipolar cycloaddition of an azomethine ylide generated from isatin and sarcosine with the dipolarophile 3-(1H-indol-3-yl)-3-Oxo-2-(2-oxoindolin- 3-ylidene)propanenitrile, and also spiro compound of acenaphthene

TL;DR: A high-throughput screen of the MLPCN library using a homogenous fluorescence polarization assay identified a small molecule as a first-in-class direct inhibitor of Keap1-Nrf2 protein-protein interaction.

TL;DR: In this manuscript, several composite parameters, or efficiency indices, are examined utilizing theoretical and experimental matched molecular pair analyses in order to understand the basis for how each will perform under varying scenarios of molecular optimizations.

TL;DR: Although the primary focus is on FBLD, many of the lessons also apply to more established approaches such as high-throughput screening, and some of the suggestions to avoid them are offered.

TL;DR: The next generation of peptidic co-agonists comprises the activity of GLP-1 plus additional gastro-intestinal hormones with the potential for increased therapeutic benefits compared to GLP -1 RAs.

TL;DR: The chemistry, biology and structure-activity trends for a series of cyanoanthranilic diamides from which cyantraniliprole was selected for commercial development are reported on.

TL;DR: The notable differences observed between nonquaternized and quaternized quinoxaline derivatives suggest that differing mechanisms of action are associated with their antibacterial properties.

TL;DR: A summary of the recently published efforts on tacrine derivatives as a renewed potential therapeutic approach for the treatment of Alzheimer's disease is presented.

TL;DR: Twenty-four most active compounds were screened by ABTS method and showed 60-90% inhibition at 5 μg/mL concentration and showed better or similar activity as compared to the reference compound ascorbic acid.

TL;DR: A series of novel coumarin-benzimidazole hybrids, 3-(1H-benzo-2-yl)-7-(substituted amino)-2H-chromen- 2-one derivatives of biological interest displayed appreciable anticancer activities against leukemia, colon cancer and breast cancer cell lines.

TL;DR: It is shown, using in vitro thioflavin T assays and transmission electron microscopy, that grape seed extract inhibits fibril formation of kappa-casein (κ-CN), a milk protein which forms amyloid fibrils spontaneously under physiological conditions and it is concluded that the gallate moiety has the fibrIL-inhibitory activity.

TL;DR: Thioether/sulfone heterocyclic derivatives could be considered as new lead compounds for antiviral studies and displayed high antiviral activity against tobacco mosaic virus.

TL;DR: The X-ray structure of SARS-CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit reorganization of the S2–S4 binding pockets leading to the first sub-micromolar noncovalent3CLpro inhibitors retaining a single amide bond.

TL;DR: Regioselective synthesis of isoxazole-mercaptobenzimidazole hybrids and their efficiency in in vivo analgesic and anti-inflammatory activity was described.

TL;DR: Oral administration of VR markedly reduced the ISO-induced increase in the levels of serum cardiac markers such as troponin-T, creatine kinase-MB, lactate dehydrogenase and glutamate pyruvate transaminase as well as cardiac lipid peroxidation suggesting its cardio-protective and free radical scavenging potential.

TL;DR: High-throughput docking into the induced-fit conformation of ZAP70 generated by molecular dynamics has revealed 10 low-micromolar inhibitors which correspond to six distinct chemotype which has an IC50 of 110 nM for JAK2.

TL;DR: The modes of action and likely specificity of these compounds are critically discussed, concluding that a suitable chemical biology tool for probing the function of Pin1 has yet to be found.

TL;DR: Structural characterization of inhibitor complexes conducted using selected GyrB/ParE orthologs aided in the identification of important steric, dynamic and compositional differences in the ATP-binding pockets of the targets, enabling the design of highly potent pyrrolopyrimidine inhibitors with broad enzymatic spectrum and dual targeting activity.

TL;DR: A series of coumarin appended formyl-pyrazoles 14-18 were synthesized by a simple and accessible approach as mentioned in this paper, which showed promising antifungal and antibacterial activity against different organisms tested.

TL;DR: Only compound 1 exhibited effective inhibitory activity against H1N1 viral neuraminidase (NA), and docking of two isomers into the active sites of NA showed that the E double bond Δ(5(10)) was essential to achieve activity.

TL;DR: Tuberculosis is a bacterial disease that predominantly affects the lungs and results in extensive tissue pathology, which contributes to the complexity of drug development as it presents discrete microenvironments within which the bacterium resides.

TL;DR: A diverse series of promising high affinity (99m)Tc/Re-tricarbonyl radiolabeled PSMA inhibitors were synthesized by the attachment of glutamate-urea-lysine and glutamate-UREa-glutamate to single amino acid chelate (SAAC) to achieve high affinity PSMA binding.

TL;DR: Compound 12c was the strongest AChE inhibitor, being 20-fold more potent than galanthamine and twofoldMore potent than tacrine, and it also had ability to inhibit Aβ aggregation (close to the reference compound) and to function as a metal chelator.

TL;DR: The cytotoxicity study with breast cancer cells and non-cancerous breast epithelial cell showed that rationally selected ligands with cancer-cell targeting ability on POM-biomolecule conjugates can impart enhanced anti-tumor activity and selectivity, thus representing a new concept to develop novel Pom-biOMolecule hybrid drugs with the potential synergistic effect: increased bioactivity and lower side effect.

TL;DR: The leaves of N. nucifera have potential as an anti-obesity agent by inhibiting pancreatic lipase and adipocyte differentiation and the relative and absolute stereochemistry of the compounds was determined by NOESY and CD spectrometry, respectively.

TL;DR: A structure-activity relationship study was performed by incorporating structural features of the anti-angiogenic multi-kinase inhibitor sorafenib into soluble epoxide hydrolase (sEH) inhibitors, suggesting a potential rational approach to control the angiogenic responses stemming from sEH inhibition.

TL;DR: Focus will be on the pharmacology supporting the contention that reported agents are truly peripherally restricted, and methodology that can be used to eliminate BBB penetration and the means to identify potential agents with little brain presence.