Bhagyesh Ramesh Sarode
Postdoctoral Scholar, Chemical and Systems Biology
Honors & Awards
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MCHRI Postdoctoral Fellowship, Stanford MCHRI (2021)
Professional Education
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Postdoctoral fellow, Stanford University, Chemical & Systems Biology
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Ph.D., University of Missouri-Kansas City, Pharmaceutical Sciences (2019)
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B.Pharm, Institute of Chemical Technology, Pharmacy (2011)
Patents
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Simon Friedman, Karthik Nadendla, Bhagyesh Sarode, Piyush Jain, Dipu Karunakaran, Swetha Chintala, Parth Shah. "United States Patent US 20200147215 Drug Conjugates with Photocleavable Solubility Modulators", The Curators of the University of Missouri, Apr 14, 2018
All Publications
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Catalytic asymmetric synthesis of meta benzene isosteres.
Nature
2024
Abstract
Although aromatic rings are common elements in pharmaceutically active compounds, the presence of these motifs brings several liabilities with respect to the developability of a drug1. Nonoptimal potency, metabolic stability, solubility and lipophilicity in pharmaceutical compounds can be improved by replacing aromatic rings with non-aromatic isosteric motifs2. Moreover, whereas aromatic rings are planar and lack three-dimensionality, the binding pockets of most pharmaceutical targets are chiral. Thus, the stereochemical configuration of the isosteric replacements may offer an added opportunity to improve the affinity of derived ligands for target receptors. A notable impediment to this approach is the lack of simple and scalable catalytic enantioselective syntheses of candidate isosteres from readily available precursors. Here we present a previously unknown palladium-catalysed reaction that converts hydrocarbon-derived precursors to chiral boron-containing nortricyclanes and we show that the shape of these nortricyclanes makes them plausible isosteres for meta disubstituted aromatic rings. With chiral catalysts, the Pd-catalysed reaction can be accomplished in an enantioselective fashion and subsequent transformation of the boron group provides access to a broad array of structures. We also show that the incorporation of nortricyclanes into pharmaceutical motifs can result in improved biophysical properties along with stereochemistry-dependent activity. We anticipate that these features, coupled with the simple, inexpensive synthesis of the functionalized nortricyclane scaffold, will render this platform a useful foundation for the assembly of new biologically active agents.
View details for DOI 10.1038/s41586-024-07865-4
View details for PubMedID 39169193
View details for PubMedCentralID 10680098
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Bicyclic caged morpholino oligonucleotides for optical gene silencing
ChemBioChem
2022
View details for DOI 10.1002/cbic.202200374