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961.
Al-Hourani BJ Sharma SK Suresh M Wuest F 《Bioorganic & medicinal chemistry letters》2012,22(6):2235-2238
A series of novel 5-substituted 1H-tetrazoles as cyclooxygenase-2 (COX-2) inhibitors was prepared via treatment of various diaryl amides with tetrachlorosilane/sodium azide. All compounds were tested in cyclooxygenase (COX) assays in vitro to determine COX-1 and COX-2 inhibitory potency and selectivity. Tetrazoles contained a methylsulfonyl or sulfonamide group as COX-2 pharmacophore displayed only low inhibitory potency towards COX-2. Most potent compounds showed IC(50) values of 6 and 7 μM for COX-2. All compounds showed IC(50) values greater 100 μM for COX-1 inhibition. 相似文献
962.
Arasappan A Bennett F Girijavallabhan V Huang Y Huelgas R Alvarez C Chen L Gavalas S Kim SH Kosinski A Pinto P Rizvi R Rossman R Shankar B Tong L Velazquez F Venkatraman S Verma VA Kozlowski J Shih NY Piwinski JJ MacCoss M Kwong CD Clark JL Fowler AT Geng F Kezar HS Roychowdhury A Reynolds RC Maddry JA Ananthan S Secrist JA Li C Chase R Curry S Huang HC Tong X Njoroge FG 《Bioorganic & medicinal chemistry letters》2012,22(9):3229-3234
Based on a previously identified HCV replication (replicase) inhibitor 1, SAR efforts were conducted around the pyrimidine core to improve the potency and pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be the optimal substituent at the pyrimidine 5-position. Due to potential reactivity concern, the 4-chloro residue was replaced by a methyl group with some loss in potency and enhanced rat in vivo profile. Extensive investigations at the C-2 position resulted in identification of compound 16 that demonstrated very good replicon potency, selectivity and rodent plasma/target organ concentration. Inhibitor 16 also demonstrated good plasma levels and oral bioavailability in dogs, while monkey exposure was rather low. Chemistry optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol. 相似文献
963.
Alegaon SG Alagawadi KR Sonkusare PV Chaudhary SM Dadwe DH Shah AS 《Bioorganic & medicinal chemistry letters》2012,22(5):1917-1921
The increase in the prevalence of multi drug-resistant and extensively drug-resistant strains of Mycobacteriumtuberculosis case demonstrates the urgent need of discovering new promising compounds with antimycobacterial activity. As part of our research program and with a aim of identifying new antitubercular drug candidates, a new class of 2-(trifluoromethyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazole derivatives has been synthesized by both conventional as well as microwave assisted method and evaluated for their in vitro antitubercular activity against M. tuberculosis H(37)Rv. Moreover, various drug-likeness properties of new compounds were predicted. Seven compounds from the series exhibited good activity with MIC in range 3.12-1.56μg/ml. The present study suggests that compounds 6b, 6c, 6d, 6e and 6f may serve as promising lead scaffolds for further generation of new anti-TB agents. 相似文献
964.
965.
Genome sequence of Serratia proteamaculans 568 revealed the presence of three family 33 chitin binding proteins (CBPs). The three Sp CBPs (Sp CBP21, Sp CBP28 and Sp CBP50) were heterologously expressed and purified. Sp CBP21 and Sp CBP50 showed binding preference to β-chitin, while Sp CBP28 did not bind to chitin and cellulose substrates. Both Sp CBP21 and Sp CBP50 were synergistic with four chitinases from S. proteamaculans 568 (Sp ChiA, Sp ChiB, Sp ChiC and Sp ChiD) in degradation of α- and β-chitin, especially in the presence of external electron donor (reduced glutathione). Sp ChiD benefited most from Sp CBP21 or Sp CBP50 on α-chitin, while Sp ChiB and Sp ChiD had major advantage with these Sp CBPs on β-chitin. Dose responsive studies indicated that both the Sp CBPs exhibit synergism ≥ 0.2 μM. The addition of both Sp CBP21 and Sp CBP50 in different ratios to a synergistic mixture did not significantly increase the activity. Highly conserved polar residues, important in binding and activity of CBP21 from S. marcescens (Sm CBP21), were present in Sp CBP21 and Sp CBP50, while Sp CBP28 had only one such polar residue. The inability of Sp CBP28 to bind to the test substrates could be attributed to the absence of important polar residues. 相似文献
966.
Ashoktaru Barat S. P. Bravo Suresh Chandra A. S. Corrêa M. I. Giombini R. N. C. Guedes Ma Huailei Kuldeep K. Lal Lu Liang Rakesh Matura Vindhya Mohindra L. O. Oliveira Ruchi Patangia Liu Qiyong Rama Shankar Sah Akanksha Singh Birender Kumar Singh Rajeev K. Singh D. S. Tosto Ratnesh K. Tripathi C. C. Vinson 《Molecular ecology resources》2012,12(6):1196-1197
This article documents the addition of 96 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Clarias batrachus, Marmota himalayana, Schizothorax richardsonii, Sitophilus zeamais and Syagrus romanzoffiana. These loci were cross‐tested on the following species: Clarias dussumeri, Clarias gariepinus, Heteropneustus fossilis, Sitophilus granarius and Sitophilus oryzae. 相似文献
967.
Sixteen organic co-solvents were screened for stereoselective reduction of 1-acetonapthone in aqueous media by whole cells of Geotrichum candidum. Benzyl alcohol was found to be a good co-solvent as it afforded a high coversion and reduced deactivation of the cells. Half-lives of the wet and lyophilized whole cell biocatalysts in pure benzyl alcohol were 23.07 and 11.21 hours, respectively. The initial reaction rates at 30°C were 13.1 and 11.0μmol/min, respectively, for the wet and lyophilized cells. With optimized conditions in a reaction medium containing phosphate buffer and benzyl alcohol (1:1 by vol) with 230mM 1-acetonapthone, more than 98% and 81% conversion (ee >99%) was achieved in 5 hours with the wet and lyophilized cells, respectively. Both the cell preparations showed maximum conversion at 30°C. A thermodynamic characterization revealed that the wet cells were more thermostable than the lyophilized cells. The calculated half-life of the wet cells at pH 7 was 93 hours, whereas that of the lyophilized cells was 71 hours at the same condition. 相似文献
968.
969.
970.