Synthetic Approaches to Contemporary Drugs that Contain the Cyclopropyl Moiety

Synthesis ◽  
2020 ◽  
Vol 52 (09) ◽  
pp. 1315-1345 ◽  
Author(s):  
Zdenko Časar
Keyword(s):  
Drug Administration ◽  
Structural Diversity ◽  
Building Blocks ◽  
Time Frame ◽  
New Drugs ◽  
Diazo Compounds ◽  
Structural Motif ◽  
Ch Acids ◽  
Synthetic Approaches ◽  
The U.S

The U.S. Food and Drug Administration approved 18 new drugs that incorporate the cyclopropyl structural motif in the time frame from 2012 to 2018. This review provides an overview of synthetic approaches to these drugs with emphasis on the construction of the cyclopropyl moiety or its incorporation into the key building blocks for assembly of the highlighted drugs. Based on the structural diversity of these drugs, synthetic approaches for the construction and introduction of the cyclopropyl moiety into their structure are diverse and include: cycloalkylation (double alkylation) of CH-acids, catalytic cyclopropanation of alkenes with diazo compounds, the Simmons–Smith reaction, the Corey–Chaykovsky reaction, the Kulinkovich reaction, the Horner–Wadsworth–Emmons reaction, and cycloaddition. In addition, the cyclopropyl structure was also introduced into the drug substance intermediates via simple cyclopropyl-moiety-containing building blocks, such as cyclopropylamine, cyclopropanesulfonamide, cyclopropanecarbonyl chloride, and cyclopropylmagnesium bromide.1 Introduction2 Synthesis of Recently Approved Cyclopropyl-Moiety-Containing Drugs2.1 Cabozantinib2.2 Trametinib2.3 Simeprevir2.4 Ledipasvir2.5 Olaparib2.6 Tasimelteon2.7 Finafloxacin2.8 Paritaprevir2.9 Lenvatinib2.10 Lumacaftor2.11 Lesinurad2.12 Grazoprevir2.13 Glecaprevir2.14 Ozenoxacin2.15 Voxilaprevir2.16 Naldemedine2.17 Tezacaftor2.18 Tecovirimat3 Conclusion

scholarly journals Modern Approaches to the Synthesis and Transformations of Practically Valuable Benzothiazole Derivatives

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2190
Author(s):  
Larisa V. Zhilitskaya ◽  
Bagrat A. Shainyan ◽  
Nina O. Yarosh
Keyword(s):  
Green Chemistry ◽  
Building Blocks ◽  
Biologically Active ◽  
New Drugs ◽  
Synthesis Methods ◽  
Atom Economy ◽  
One Pot ◽  
Benzothiazole Derivatives ◽  
Pharmacologically Active ◽  
Synthetic Approaches

The review is devoted to modern trends in the chemistry of 2-amino and 2-mercapto substituted benzothiazoles covering the literature since 2015. The reviewed heterocycles belong to biologically active and industrially demanded compounds. Newly developed synthesis methods can be divided into conventional multistep processes and one-pot, atom economy procedures, realized using green chemistry principles and simple reagents. The easy functionalization of the 2-NH2 and 2-SH groups and the benzene ring of the benzothiazole moiety allows considering them as highly reactive building blocks for organic and organoelement synthesis, including the synthesis of pharmacologically active heterocycles. The review provides a summary of findings, which may be useful for developing new drugs and materials and new synthetic approaches and patterns of reactivity.

scholarly journals Chiral Flavonoids as Antitumor Agents

2021 ◽  
Vol 14 (12) ◽  
pp. 1267
Author(s):  
Cláudia Pinto ◽  
Honorina Cidade ◽  
Madalena Pinto ◽  
Maria Elizabeth Tiritan
Keyword(s):  
Antitumor Activity ◽  
Antitumor Agents ◽  
Biological Activities ◽  
Structural Diversity ◽  
Building Blocks ◽  
Inhibitory Effect ◽  
Chiral Molecules ◽  
Growth Inhibitory ◽  
Synthetic Approaches

Flavonoids are a group of natural products with a great structural diversity, widely distributed in plant kingdom. They play an important role in plant growth, development and defense against aggressors. Flavonoids show a huge variety of biological activities such as antioxidant, anti-inflammatory, anti-mutagenic, antimicrobial and antitumor, being able to modulate a large diversity of cellular enzymatic activities. Among natural flavonoids, some classes comprise chiral molecules including flavanones, flavan-3-ols, isoflavanones, and rotenoids, which have one or more stereogenic centers. Interestingly, in some cases, individual compounds of enantiomeric pairs have shown different antitumor activity. In nature, these compounds are mainly biosynthesized as pure enantiomers. Nevertheless, they are often isolated as racemates, being necessary to carry out their chiral separation to perform enantioselectivity studies. Synthetic chiral flavonoids with promising antitumor activity have also been obtained using diverse synthetic approaches. In fact, several new chiral bioactive flavonoids have been synthesized by enantioselective synthesis. Particularly, flavopiridol was the first cyclin-dependent kinase (CDK) inhibitor which entered clinical trials. The chiral pool approaches using amino acid as chiral building blocks have also been reported to achieve small libraries of chrysin derivatives with more potent in vitro growth inhibitory effect than chrysin, reinforcing the importance of the introduction of chiral moieties to improve antitumor activity. In this work, a literature review of natural and synthetic chiral flavonoids with antitumor activity is reported for the first time.

scholarly journals The emperor's new drugs: An analysis of antidepressant medication data submitted to the U.S. Food and Drug Administration.

2002 ◽  
Vol 5 (No Issue Specified) ◽  
pp. No First Page Specified-No Last Page Specified ◽  
Author(s):  
Irving Kirsch ◽  
Thomas J. Moore ◽  
Alan Scoboria ◽  
Sarah S. Nicholls
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
Antidepressant Medication ◽  
New Drugs ◽  
The U.S

The Drug Regulatory System of the United States Food and Drug Administration: A Defense of Current Requirements for Safety and Efficacy

1974 ◽  
Vol 4 (1) ◽  
pp. 95-107 ◽  
Author(s):  
Henry E. Simmons
Keyword(s):  
Drug Administration ◽  
Food And Drug Administration ◽  
Regulatory System ◽  
The United States ◽  
New Drugs ◽  
Safety And Efficacy ◽  
Regulatory Policies ◽  
New Drug ◽  
United States Food ◽  
The U.S

The 1962 Amendments to the Food, Drug, and Cosmetic Act have substantially increased the accountability of manufacturers of new drugs, both by raising standards for clinical testing as well as requiring, for the first time, a demonstration of proof of efficacy. Critics of the new regulatory system of the Food and Drug Administration (FDA) which imposes the requirements, have called for the repeal of the new standards on the grounds that they are stringent to the point of being counterproductive, reflect an unwarranted and excessive concern over drug safety, and have jeopardized the position of the U.S. in the worldwide development of new drugs. The author defends the regulatory system against these criticisms by demonstrating the importance of the scientific standards it has deemed essential for evaluating and approving new drug applications. Evidence of tragedy caused by inefficacious and unsafe drugs used in other countries but not in the U.S. supports FDA concern over safety and efficacy, and indicates that through its caution, the U.S. has doubtlessly been spared similar tragedy. Finally, worldwide trends in new drug development are investigated and it is shown that many factors are involved in the variation in the number and variety of drugs introduced in the marketplace of any given country which have nothing to do with its regulatory policies. It is concluded that FDA's regulatory system serves to assure the safety and efficacy of all drugs introduced into this country, while at the same time, continues to support and encourage the development of significant new drugs.

Novel Drugs and Biologics of 2016: A Boom for Neurodrugs in the Pipelin

2017 ◽  
Vol 10 (5) ◽  
pp. 3809-3814
Author(s):  
D Samba Reddy
Keyword(s):  
Muscular Atrophy ◽  
Clinical Care ◽  
New Drugs ◽  
Essential Medicines ◽  
High Demand ◽  
The Past ◽  
Novel Drugs ◽  
Innovative Products ◽  
Cns Drugs ◽  
The U.S

This article provides a brief overview of novel drugs approved by the U.S. FDA in 2016.  It also focuses on the emerging boom in the development of neurodrugs for central nervous system (CNS) disorders. These new drugs are innovative products that often help advance clinical care worldwide, and in 2016, twenty-two such drugs were approved by the FDA. The list includes the first new drug for disorders such as spinal muscular atrophy, Duchenne muscular dystrophy or hallucinations and delusions of Parkinson’s disease, among several others. Notably, nine of twenty-two (40%) were novel CNS drugs, indicating the industry shifting to neurodrugs. Neurodrugs are the top selling pharmaceuticals worldwide, especially in America and Europe. Therapeutic neurodrugs have proven their significance many times in the past few decades, and the CNS drug portfolio represents some of the most valuable agents in the current pipeline. Many neuroproducts are vital or essential medicines in the current therapeutic armamentarium, including dozens of “blockbuster drugs” (drugs with $1 billion sales potential).  These drugs include antidepressants, antimigraine medications, and anti-epilepsy medications. The rise in neurodrugs’ sales is predominantly due to increased diagnoses of CNS conditions. The boom for neuromedicines is evident from the recent rise in investment, production, and introduction of new CNS drugs.  There are many promising neurodrugs still in the pipeline, which are developed based on the validated “mechanism-based” strategy. Overall, disease-modifying neurodrugs that can prevent or cure serious diseases, such as multiple sclerosis, epilepsy, and Alzheimer’s disease, are in high demand. 

Synthetic Approaches to the 2007 New Drugs

2008 ◽  
Vol 8 (14) ◽  
pp. 1526-1548 ◽  
Author(s):  
Kevin Liu ◽  
Subas Sakya ◽  
Christopher O'Donnell ◽  
Jin Li
Keyword(s):  
New Drugs ◽  
Synthetic Approaches
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