Lamivudine, an important drug in aids treatment

Vasconcelos, Thatyana R. A.; Ferreira, Maria Lurdes; Gonçalves, Rinaldo; Silva, E. T. Da; Souza, Marcus V. N. de

doi:10.1080/17415990802183876

Cited by 6 publications

(5 citation statements)

References 26 publications

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“…Compound (2) showed good antiviral activity that has structural resemblance to Lamivudine which is a drug used to prevent and treat HIV/AIDS [35]. Compounds (7a) and (7c) are isoxazoline derivatives.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Evaluation of The Antiviral Activity of Novel 2-Thiopyrimidine-5-Carbonitrile Derivatives

et al. 2022

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2-Thiouracil-5-carbonitriles are promising compounds that have been prepared in the last twenty years and have proven to have a diversity of biological activity. In line with this approach, our new compounds were prepared starting from Biginilli condensation of thiourea, ethyl cyanoacetate and 2,4-dichlorobenzaldehyde in basic medium to give a thiouracil derivative (1) which was subjected to chlorination at4 th position by POCl3/PCl5 mixture producing chloropyrimidine (2) which in turns was reacted with m-aminoacetophenone in pyridine yielding acetyl derivative (3) which was condensed with a series of four aromatic aldehydes in alcoholic sodium hydroxide producing chalcones (4a-d) which were used as starting materials for the preparation of many heterocyclic nuclei by their reaction with hydrazine, phenyl hydrazine, hydroxylamine HCl, thiourea, ethyl cyanoacetate /ammonium acetate, malononitrile, ethyl cyanoacetate/acetic acid/sodium acetate to give pyrazoline, phenyl pyrazoline, isoxazoline, thiopyrimidine, pyridinone, aminopyridine and aminopyran derivatives (5a-d) to (11a-d) respectively . Some of the newly synthesized compounds were investigated as antiviral agents. Compounds (2), (7a), and (7c) show promising antiviral activity against Bovine Viral Diarrhea Virus (BVDV). The structures of the newly synthesized compounds were confirmed by elemental analysis in addition to spectral data and physical methods.

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Section: Resultsmentioning

confidence: 99%

Synthesis and Evaluation of The Antiviral Activity of Novel 2-Thiopyrimidine-5-Carbonitrile Derivatives

et al. 2022

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“…Interestingly, both Lamivudine and Emtricitabine are also examples of “L” nucleosides, the mirror image enantiomers of the naturally occurring “D” nucleosides which will be discussed later in this review. They also feature a sulfur atom instead of a 3′ carbon in the sugar ring (Liotta and Painter, 2016; Vasconcelos et al, 2008). Since the natural nucleosides are “D” nucleosides, it had long been thought that their unnatural enantiomers (non-superimposable mirror images) would not be recognized in biological systems.…”

Section: Modifications To the Sugar Scaffoldmentioning

confidence: 99%

“…Since the natural nucleosides are “D” nucleosides, it had long been thought that their unnatural enantiomers (non-superimposable mirror images) would not be recognized in biological systems. This proved not to be the case and both were ultimately approved for the use against HIV and Hepatitis B Virus (HBV) after demonstrating low levels of toxicity and diminished side effects compared to the aforementioned chain terminators, including AZT (De Clercq, 2012; Liotta and Painter, 2016; Vasconcelos et al, 2008; Doong et al, 1991).…”

Section: Modifications To the Sugar Scaffoldmentioning

confidence: 99%

The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold

2018

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This is the first of two invited articles reviewing the development of nucleoside-analogue antiviral drugs, written for a target audience of virologists and other non-chemists, as well as chemists who may not be familiar with the field. Rather than providing a simple chronological account, we have examined and attempted to explain the thought processes, advances in synthetic chemistry and lessons learned from antiviral testing that led to a few molecules being moved forward to eventual approval for human therapies, while others were discarded. The present paper focuses on early, relatively simplistic changes made to the nucleoside scaffold, beginning with modifications of the nucleoside sugars of Ara-C and other arabinose-derived nucleoside analogues in the 1960's. A future paper will review more recent developments, focusing especially on more complex modifications, particularly those involving multiple changes to the nucleoside scaffold. We hope that these articles will help virologists and others outside the field of medicinal chemistry to understand why certain drugs were successfully developed, while the majority of candidate compounds encountered barriers due to low-yielding synthetic routes, toxicity or other problems that led to their abandonment.

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“…Lamivudine (3TC) and emtricitabine (FTC), both nucleoside analogues, are high-dosage/high-demand drugs and manufactured in large volumes (>10 6 kg/yr). 1 In view of the global health applications, the active pharmaceutical ingredient (API) price (∼$100/kg) is the major cost contributor toward delivering these medicines to patients. The Medicines for All Institute (M4ALL) seeks to facilitate positive market conditions by creating low-cost API routes to help balance the needs of procurers and producers.…”

Section: Introductionmentioning

confidence: 99%

A Continuous Flow Sulfuryl Chloride-Based Reaction—Synthesis of a Key Intermediate in a New Route toward Emtricitabine and Lamivudine

Souza

Berton

Snead

et al. 2020

Org. Process Res. Dev.

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We demonstrate a continuous two-step sequence in which sulfenyl chloride is formed, trapped by vinyl acetate, and chlorinated further via a Pummerer rearrangement. These reactions produce a key intermediate in our new approach to the oxathiolane core used to prepare the antiretroviral medicines emtricitabine and lamivudine. During batch scale-up to tens of grams, we found that the sequence featured a strong exotherm and evolution of hydrogen chloride and sulfur dioxide. Keeping gaseous byproducts in solution and controlling the temperature led to better outcomes. These reactions are ideal candidates for implementation in a continuous mesoscale system for the sake of superior control. In addition, we found that fast reagent additions at controlled temperatures decreased byproduct formation. Herein we discuss the flow implementation and the final reactor design that led to a system with a 141 g/h throughput.

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Lamivudine, an important drug in aids treatment

Cited by 6 publications

References 26 publications

Synthesis and Evaluation of The Antiviral Activity of Novel 2-Thiopyrimidine-5-Carbonitrile Derivatives

Synthesis and Evaluation of The Antiviral Activity of Novel 2-Thiopyrimidine-5-Carbonitrile Derivatives

The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold

A Continuous Flow Sulfuryl Chloride-Based Reaction—Synthesis of a Key Intermediate in a New Route toward Emtricitabine and Lamivudine

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