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Potential Leads (potential + lead)

Distribution by Scientific Domains

Chemistry	100%

Selected Abstracts

Enantiomeric separation and determination of absolute stereochemistry of asymmetric molecules in drug discovery,Building chiral technology toolboxes,

CHIRALITY, Issue 9 2007
Oliver McConnell
Abstract The application of Chiral Technology, or the (extensive) use of techniques or tools for the determination of absolute stereochemistry and the enantiomeric or chiral separation of racemic small molecule potential lead compounds, has been critical to successfully discovering and developing chiral drugs in the pharmaceutical industry. This has been due to the rapid increase over the past 10,15 years in potential drug candidates containing one or more asymmetric centers. Based on the experiences of one pharmaceutical company, a summary of the establishment of a Chiral Technology toolbox, including the implementation of known tools as well as the design, development, and implementation of new Chiral Technology tools, is provided. Chirality, 2007. © 2007 Wiley-Liss, Inc. [source]

Explicitly correlated SCF study of anharmonic vibrations in (H2O)2

INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 4-5 2002
Donald D. Shillady
Abstract Modeling solvation in high-pressure liquid chromatography (HPLC) requires calculation of anharmonic vibrational frequencies of solvent clusters for a statistical partition function. An efficient computational method that includes electron correlation is highly desirable for large clusters. A modified version of the "soft Coulomb hole" method of Chakravorty and Clementi has recently been implemented in a Gaussian-lobe-orbital (GLO) program (PCLOBE) to include explicit electron,electron correlation in molecules. The soft Coulomb hole is based on a modified form of Coulomb's law: An algorithm has been developed to obtain the parameter "w" from a polynomial in the effective scaling of each primitive Gaussian orbital relative to the best single Gaussian of the H1s orbital. This method yields over 90% of the correlation energy for molecules of low symmetry for which the original formula of Chakravorty and Clementi does not apply. In this work, all the vibrations of the water dimer are treated anharmonically. A quartic perturbation of the harmonic vibrational modes is constrained to be equal to the exact Morse potential eigenvalue based on a three-point fit. This work evaluates the usefulness of fitting a Morse potential to a hydrogen bond vibrational mode and finds it to be slightly better than using MP2 vibrational analysis for this important dimer. A three-point estimate of the depth, De, of a Morse potential leads to a correction formula for anharmonicity in terms of the perturbed harmonic frequency: When scaled by 0.9141, the harmonic Morse method leads to essentially the same results as scaling the BPW91 local density method by 0.9827. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002 [source]

Nematicidal activity of anion transport blockers against Meloidogyne incognita, Caenorhabditis elegans and Heterorhabditis bacteriophora

PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 6 2008
Dhana Raj Boina
Abstract BACKGROUND: Because methyl bromide has been phased out as a soil sterilant, new nematicides are urgently needed. Four different chemical classes of organic acids acting as anion transport (AT) blockers were tested against a free-living nematode, Caenorhabditis elegans Maupas, a plant-parasitic nematode, Meloidogyne incognita (Kofoid and White) Chitwood, and an entomopathogenic nematode, Heterorhabditis bacteriophora Poinar, in toxicity bioassays. The materials tested were DIDS (4,4,-diisothiocyanatostilbene-2,2,-disulfonic acid), 9-AC (anthracene-9-carboxylic acid), NPPB [5-nitro-2-(3-phenylpropylamino)benzoic acid] and IAA-94 (indanyloxyacetic acid). RESULTS: All the compounds showed slowly developing nematicidal activity against second-stage juveniles of M. incognita and adults of C. elegans, but not against H. bacteriophora infective-stage juveniles. The LC50 values of these compounds were < 50 mg L,1 after 48 and 72 h incubation, while at 168 h incubation the LC50 values were < 10 mg L,1 for both sensitive species. Across both species and time, the LC50 values generally differed no more than twofold among the four compounds tested in this study. In contrast, none of the compounds (200 mg L,1) caused more than control mortality to H. bacteriophora, even after 168 h of incubation. CONCLUSION: These compounds are potential leads for commercial nematicides. The insensitivity to H. bacteriophora is consistent with the natural exposure of this nematode to DST (3,5-dihydroxy-4-isopropylstilbene), a stilbene produced by its symbiotic bacterium. Based on the known activity of the compounds used in this study, it is suggested that anion transporters form the probable target sites for DIDS, 9-AC, NPPB and IAA-94 in nematodes. Copyright © 2008 Society of Chemical Industry [source]

Synthesis, Antiproliferative Evaluation, and Structure,Activity Relationships of 3-Arylquinolines

CHEMMEDCHEM, Issue 10 2008
Zhu-Ping Xiao
The cytotoxicity of substituted 3-aryl-4-chloroquinolines: A series of 3-arylquinolines were designed, synthesized and evaluated as antitumor agents. While the majority of the 34 compounds evaluated exhibited potent cytotoxicity in one or more of the human tumor cell lines tested, two compounds were identified as potential leads, with high activity against human hepatocellular liver carcinoma (Hep-G2), human erythromyeloblastoid leukemia (K562) and human oral epidermoid carcinoma (KB) cell lines, and lacking significant cytotoxicity against the normal human liver cell line (L02). [source]

A Combinatorial Approach to 2,4,6-Trisubstituted Triazines with Potent Antimalarial Activity: Combining Conventional Synthesis and Microwave-Assistance

CHEMMEDCHEM, Issue 6 2008
Sergio Melato Dr.
Managing malaria. Malaria is responsible for two million deaths per year particularly in developing countries, therefore there is great need for the development of cost effective treatment. The synthesis of a library of trisubstituted triazines with potent antimalarial in,vitro activity is reported. Among them, five products may be developed as potential leads in the search for new drugs against plasmodial chloroquine-resistant strains. [source]