Recent advances made in the synthesis of small drug molecules for clinical applications: An insight

Abstract

Over decades dependency of humans on the drugs has become indispensable and irreplaceable. Thus, each year many new drugs are licensed. Nonetheless, drugs undergo rigorous testing and analysis to be available globally in economic price for the suitability of patients with different age and physiological conditions. The testing of drugs include phase I clinical trial using small group of 20–100 healthy volunteers for safety, pharmacology and efficacy; phase II clinical trial using 100–500 volunteer patients to optimize effective dose, dose interval, safety analysis and mode of delivery such as oral or intravenous; phase III clinical trial using 1000–5000 in a larger population of patients globally at different international places to collect sufficient safety and efficacy data for patenting and licencing. Moreover, thousands of drugs fail to achieve these objectives. Therefore, this mini-review intends to critically examine and assimilate the clinical applications of selected complex repurposed small drug molecules which are in different phase of trials for treating viral infection including complications due to COVID-19: (a) Remdesivir, (b) Galidesivir, (c) Favipiravir, (d) Baricitinib, and (e) Baloxavir.

Significance of Immune Status of SARS-CoV-2 Infected Patients in Determining the Efficacy of Therapeutic Interventions

“…As per the news reports, India-based enterprise Glenmark has secured government approval for the large-scale manufacturing and antiviral Favipiravir drug to treat SARS-CoV-2 infected patients [ 27 ]. Furthermore, molnupiravir parent drug (NHC) combination of drugs against SARS-CoV-2 viruses are recommended in a trial version of the treatment plan [ 28 ], including ritonavir/ralproveravir or ribavirin by intravenous injection in addition to the inhalation of alpha interferon [ 26 ].…”

Molecular Docking Studies of Rifampicin – rpoB complex: Repurposing Drug Design Implications for against Plasmodium falciparum Malaria through a Computational Approach

“…Due to its prokaryotic nature the apicoplast has generated immense interest as a putative drug target for malaria, which could be exploited to develop new antimalarial compounds directed specifically against this deadly human [29]. Many compounds targeting these plastid pathways are antimalarial and have favorable profiles based on extensive knowledge from their use as antibacterial.…”

An economical and practical procedure of favipiravir synthesis for the treatment of Covid-19

“…Various strategies reported for the favipiravir synthesis as summarized in Scheme 1 . Accordingly, favipiravir could be synthesized starting from 3-aminopyrazine-2-carboxylic acid ( 3 ) (Furuta and Egawa 2000 ; Liu et al 2017 ), 3-hydroxy-6-nitropyrazine-2-carboxamide ( 4 ) (Jordis and Beldar 2009 ), pyrazine-2-carbonitrile ( 5 ) (Mengyang 2017 ; Wang et al 2017 ), 2-aminopyrazine ( 6 ) (Guo et al 2019 ), 2-aminomalonamide ( 7 ) (Hara et al 2011 ), diethyl malonate ( 8 ) (Tiyasakulchai et al 2021 ), 3-hydroxypyrazine-2-carboxylic acid ( 9 ) (Shi et al 2014 ), and ethyl diethoxyacetate ( 10 ) (Nakamura et al 2015 ), as reviewed earlier (Titova and Fedorova 2020 ; Gouda and Qurban 2021 ; Tiyasakulchai et al 2021 ; Arora et al 2021 ).

Scheme 1 General routes with different starting materials ( 3–10 ) reported for the favipiravir synthesis

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