Design, synthesis, and identification of silicon incorporated oxazolidinone antibiotics with improved brain exposure
| Title | Design, synthesis, and identification of silicon incorporated oxazolidinone antibiotics with improved brain exposure |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Seetharamsingh, B, Ramesh, R, Dange, SS, Khairnar, PV, Singhal, S, Upadhyay, D, Veeraraghavan, S, Viswanadha, S, Vakkalanka, S, D. Reddy, S |
| Journal | ACS Medicinal Chemistry Letters |
| Volume | 6 |
| Issue | 11 |
| Pagination | 1105-1110 |
| Date Published | NOV |
| ISSN | 1948-5875 |
| Keywords | Antibacterial, brain exposure, linezolid, oxazolidinone, sila analogue |
| Abstract | 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. |
| DOI | 10.1021/acsmedchemlett.5b00213 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 3.355 |
Divison category:
Organic Chemistry