@article {48764,
	title = {Scalable synthesis of silacyclohexanones and ready access to silicon building blocks},
	journal = {Organic Letters},
	volume = {25},
	year = {2023},
	month = {SEP },
	pages = {6881-6885},
	type = {Article},
	abstract = {<p>
	A simple and efficient two-step method for the synthesis of silacyclohexanones starting from bis(bromoethylsilanes) using TosMIC is presented. The prepared silacyclohexanones were transformed to nine different heterocycles with silicon incorporation. In addition, the developed methodology was used for the synthesis of a sila analogue of the HDAC6 inhibitor tubastatin A.</p>
},
	issn = {1523-7060},
	doi = {10.1021/acs.orglett.3c02561},
	author = {Ramesh, Eagala and Nandawadekar, Laxman D. and Rao, Ramana Sreenivasa and Reddy, D. Srinivasa}
}
@article {49727,
	title = {Silicon incorporated tacrine: design, synthesis, and evaluation of biological and pharmacokinetic parameters},
	journal = {RSC Medicinal Chemistry},
	volume = {16},
	year = {2025},
	month = {JUN},
	pages = {2603-2614},
	type = {Article},
	abstract = {<p>
	Tacrine, an orally bioavailable cholinesterase inhibitor, was previously used to treat Alzheimer{\textquoteright}s disease but was withdrawn due to hepatotoxicity. The unique structural features of tacrine have once again captured the interest of medicinal chemists. However, the blood-brain barrier (BBB) permeability hampered the development of the majority of its new analogs. Herein, we employed a silicon switch approach for improving the BBB permeability of CNS drugs with tacrine as a tool compound. The replacement of C2 methylene of tacrine with dimethyl silicon yielded {\textquoteleft}sila-tacrine{\textquoteright} that inhibits acetylcholinesterase as well as butyrylcholinesterase with IC50 values of 3.18 and 6.09 mu M, respectively. Sila-tacrine competitively inhibits acetylcholinesterase while it is a non-competitive inhibitor of butyrylcholinesterase. The molecular docking results corroborated with the in vitro cholinesterase inhibition activity of tacrine vs. sila-tacrine. Sila-tacrine demonstrated metabolic stability in HLM and MLM and exhibited superior plasma exposure in an oral pharmacokinetic study in Swiss albino mice. However, tissue distribution studies revealed lower-than-expected brain levels due to efflux pump-mediated transport. This study offers a proof-of-concept for the silicon switch approach in improving the BBB permeability of CNS-active compounds.</p>
},
	doi = {10.1039/d5md00019j},
	author = {Kulkarni, Akshay S. and Ramana, Sreenivasa Rao and Nuthakki, Vijay K. and Bhatt, Shipra and Jamwal, Ashiya and Nandawadekar, Laxman D. and Jotshi, Anshika and Kumar, Ajay and Nandi, Utpal and Bharate, Sandip B. and Reddy, D. Srinivasa}
}
