Computer-generated “synthetic contingency” plans at times of logistics and supply problems: scenarios for hydroxychloroquine and remdesivir

Abstract

<p>A computer program for retrosynthetic planning helps develop multiple “synthetic contingency” plans for hydroxychloroquine and also routes leading to remdesivir, both promising but yet unproven medications against COVID-19.</p>

Reinforcing the Supply Chain of COVID-19 Therapeutics with Expert-Coded Retrosynthetic Software

“…In most cases the proposed route has the same number, or fewer, steps than the established routes, and initiates from distinct starting materials. Our search for routes to 1 in the SYNTHIA TM software yielded a retrosynthetic solution that effectively reproduced a route predicted by the Grzybowski lab, 16 which was very similar to the route published by the drug's maker, Gilead Sciences, Inc., 25 except for variations in protecting groups. One route we found proposed installation of the C15 stereocenter via amination of a chiral enolate (for details, see Ref.…”

Engines of discovery: Computers in advanced synthesis planning and identification of drug candidates

“…In fact, in ref 26 , we showed how these capabilities can be used to navigate around patented routes and how they can be used to design economical and green routes leading, for instance, to several blockbuster drugs. In a similar genre, in very recent work by us 27 and by Cernak's team, 28 the imposed constraint was to avoid the key intermediates used in the production of antivirals potentially relevant in the context of the current COVID-19 pandemic. In this task, Chematica designed as many as 17 alternative routes to one target whereas Cernak used the program not only to plan alternative syntheses but also carried many of them in the laboratory, validating Chematica's plans once again.…”

COVID‐19 into Chemical Science Perspective: Chemical Preventive Measures and Drug Development

“…There have been several reviews published recently on COVID‐19 addressing the recent advancement on the analysis, testing and treatment of this virus [10–43] . In this review, we have discussed COVID‐19 facts and literature starting from host binding events of SARS‐CoV‐2, chemical preventive measures and synthesis of repurposed drugs into chemical science perspective.…”

“…[1,8,9] Personal preventive measures [10] including chemical protective measures such as soap water, bleach solution, alcohol-based hand sanitizers, and hydrogen peroxide have been conceptualized and prepared to destroy the viruses. [11] Advancement of various testing tools, [12][13][14][15][16][17][18][19] antiviral drugs, [20][21][22][23][24][25][26][27][28][29] vaccines, [30][31][32] and other medical involvements [10] are being developed in a fast-paced manner. These activities apparently seem far away from the areas of chemistry which usually deal with elements and chemical compounds.…”