01792nas a2200313   4500008004100000022001400041245012100055210006900176260007100245300001400316490000600330520070200336653001801038653001901056653001401075653001801089653001801107100002301125700001801148700002801166700002501194700001901219700002001238700002701258700002401285700002401309700002101333856012401354       2015                        eng d  a1948-587500aDesign, synthesis, and identification of silicon incorporated oxazolidinone antibiotics with improved brain exposure0 aDesign synthesis and identification of silicon incorporated oxaz  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcNOV  a1105-11100 v63 a<p>Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon. Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, three compounds from this series demonstrated up to a 30-fold higher brain/plasma ratio when compared to linezolid thereby indicating their therapeutic potential in brain associated disorders.</p>10aAntibacterial10abrain exposure10alinezolid10aoxazolidinone10asila analogue1 aSeetharamsingh, B.1 aRamesh, Remya1 aDange, Santoshkumar, S.1 aKhairnar, Pankaj, V.1 aSinghal, Smita1 aUpadhyay, Dilip1 aVeeraraghavan, Sridhar1 aViswanadha, Srikant1 aVakkalanka, Swaroop1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/design-synthesis-and-identification-silicon-incorporated-oxazolidinone-antibiotics-001454nas a2200241   4500008004100000245012100041210006900162260000800231300001200239490000800251520062500259100001800884700002400902700001700926700001900943700001500962700002700977700002401004700002001028700002401048700002101072856011901093       2016                        eng d00aRepurposing of a drug scaffold: identification of novel sila analogues of rimonabant as potent antitubercular agents0 aRepurposing of a drug scaffold identification of novel sila anal  cOCT  a723-7300 v1223 a<p>The structural similarity between an MmpL3 inhibitor BM212, and a cannabinoid receptor modulator rimonabant, prompted us to investigate the anti-tubercular activity of rimonabant and its analogues. Further optimization, particularly through incorporation of silicon into the scaffold, resulted in new compounds with significant improvement in anti-tubercular activity against Mycobacterium tuberculosis (H37Rv). The sila analogue 18a was found to be the most potent antimycobacterial compound (MIC, 31 ng/mL) from this series with an excellent selectivity index. (C) 2016 Elsevier Masson SAS. All rights reserved.</p>1 aRamesh, Remya1 aShingare, Rahul, D.1 aKumar, Vinod1 aAnand, Amitesh1 aSwetha, B.1 aVeeraraghavan, Sridhar1 aViswanadha, Srikant1 aUmmanni, Ramesh1 aGokhale, Rajesh, S.1 aReddy, Srinivasa  uhttps://library.ncl.res.in/content/repurposing-drug-scaffold-identification-novel-sila-analogues-rimonabant-potent