Recent synthetic methodologies for pyrazolo[1,5-<i>a</i>]pyrimidine

Salem, Mohamed Salem Ould Ahmedou; Helal, Mohamed H.; Gouda, Moustafa A.; El‐Gawad, Hala H. Abd; Shehab, Marwa A. M.; El-Khalafawy, Abeer

doi:10.1080/00397911.2019.1604967

Cited by 36 publications

(26 citation statements)

References 67 publications

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“…Recent reviews cover synthetic methodologies using 3(5)-aminopyrazoles as buildings blocks to the present state of the art [13,16,107]. However, the majority of these works fail to explain the discrepancies noted in somewhat similar conditions and reactivity aspects linked to the tautomeric precursor are elusive.…”

Section: (5)-aminopyrazole In Heterocyclic Synthesismentioning

confidence: 99%

“…As the name suggests, this chemotype results from fusion of two heterocyclic systems: the pyrazole ring and the pyrimidine ring. From a synthetic point of view, the pyrazolo[1,5-a]pyrimidine scaffold can be obtained by employing different strategies [15][16][17], including the condensation of the 3(5)-aminopyrazole precursor with 1,3-dielectrophilic agents.…”

Section: Intramolecular Cyclization Of 3(5)-aminopyrazolementioning

confidence: 99%

“…The rich reactivity of pyrazoles is linked to their challenging structure, with the possibility of tautomerism [12] and the presence of a multifarious framework, offering versatility for applications in synthetic organic chemistry [13,14]. Derivatives of 3-or 5-amino pyrazole, generally referred to as 3(5)-aminopyrazoles, are especially interesting in this context, serving as starting materials for the synthesis of condensed heterocycles, including pyrazolo [1,5-a]pyrimidines, another privileged motif that attracted interest for many years and is extensively reviewed, in the past and also in recent literature [15][16][17][18]. However, to this date, a thorough investigation regarding the chemistry and diverse reactivity of 3(5)-aminopyrazoles leading to more complex heterocyclic systems has not been performed.…”

Section: Introductionmentioning

confidence: 99%

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Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazoles

2019

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Pyrazoles are known as versatile scaffolds in organic synthesis and medicinal chemistry, often used as starting materials for the preparation of more complex heterocyclic systems with relevance in the pharmaceutical field. Pyrazoles are also interesting compounds from a structural viewpoint, mainly because they exhibit tautomerism. This phenomenon may influence their reactivity, with possible impact on the synthetic strategies where pyrazoles take part, as well as on the biological activities of targets bearing a pyrazole moiety, since a change in structure translates into changes in properties. Investigations of the structure of pyrazoles that unravel the tautomeric and conformational preferences are therefore of upmost relevance. 3(5)-Aminopyrazoles are largely explored as precursors in the synthesis of condensed heterocyclic systems, namely pyrazolo[1,5-a]pyrimidines. However, the information available in the literature concerning the structure and chemistry of 3(5)-aminopyrazoles is scarce and disperse. We provide a revision of data on the present subject, based on investigations using theoretical and experimental methods, together with the applications of the compounds in synthesis. It is expected that the combined information will contribute to a deeper understanding of structure/reactivity relationships in this class of heterocycles, with a positive impact in the design of synthetic methods, where they take part.

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Section: (5)-aminopyrazole In Heterocyclic Synthesismentioning

confidence: 99%

Section: Intramolecular Cyclization Of 3(5)-aminopyrazolementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazoles

2019

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“…This fused pyrazole is a privileged scaffold for combinatorial library design and drug discovery because its great synthetic versatility permits structural modifications throughout its periphery. The PP derivatives synthesis has been widely studied; thus, various reviews related to the obtention and later derivatization steps have been described in the literature [ 2 , 3 , 4 , 5 ], after the first critical review involving this attractive scaffold [ 6 ] ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold

2021

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Pyrazolo[1,5-a]pyrimidine (PP) derivatives are an enormous family of N-heterocyclic compounds that possess a high impact in medicinal chemistry and have attracted a great deal of attention in material science recently due to their significant photophysical properties. Consequently, various researchers have developed different synthesis pathways for the preparation and post-functionalization of this functional scaffold. These transformations improve the structural diversity and allow a synergic effect between new synthetic routes and the possible applications of these compounds. This contribution focuses on an overview of the current advances (2015–2021) in the synthesis and functionalization of diverse pyrazolo[1,5-a]pyrimidines. Moreover, the discussion highlights their anticancer potential and enzymatic inhibitory activity, which hopefully could lead to new rational and efficient designs of drugs bearing the pyrazolo[1,5-a]pyrimidine core.

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“…So far, different synthetic routes towards pyrazolo [1,5-a]pyrimidines have been reported. These methods have been mainly included the condensation of 3-aminopyrazoles with 1,3-bis electrophilic substrates [51][52][53][54][55][56][57][58][59] , 1,2-allenic lactones 60 , β-halovinyl aldehyde 61 , and activated alkynes 62,63 .…”

mentioning

confidence: 99%

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

Peytam

Adib

Shourgeshty

et al. 2020

Sci Rep

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In an attempt to find novel α-glucosidase inhibitors, an efficient, straightforward reaction to synthesize a library of fully substituted 6-amino-pyrazolo[1,5-a]pyrimidines 3 has been investigated. Heating a mixture of α-azidochalcones 1 and 3-aminopyrazoles 2 under the mild condition afforded desired compounds with a large substrate scope in good to excellent yields. All obtained products were evaluated as α-glucosidase inhibitors and exhibited excellent potency with IC 50 values ranging from 15.2 ± 0.4 µM to 201.3 ± 4.2 µM. Among them, compound 3d was around 50-fold more potent than acarbose (IC 50 = 750.0 ± 1.5 µM) as standard inhibitor. Regarding product structures, kinetic study and molecular docking were carried out for two of the most potent ones. Recently, the world health organization (WHO) has identified the diabetes mellitus (DM) as a critical health challenge in the 21st century. The prevalence of diabetes has been increasing at alarming rate over the past three decades. This metabolic disorder, characterized by chronic hyperglycemia, leads to further severe damages like abnormally great thrust, excessive appetite, overweigh, blindness, excessive urination, cardiovascular complications, as well as renal and neurodegenerative diseases 1-6. There are three main diabetes types among which type 2 or non-insulin dependent (T2DM) is the most common one, mainly treated by controlling the digestive enzyme activities such as α-glucosidase 7-9. α-Glucosidase, found in the brush-border surface membrane of intestinal cells, plays catalyzing role in the carbohydrate digestion process by which the postprandial blood glucose levels increases. Preventing the glucose release in the bloodstream, the α-glucosidase inhibitors control T2DM 10. Additionally, this enzyme has a pivotal role in the biosynthesis of glycoprotein, therefore, its inhibitors have possessed anticancer, antitumor, antiviral, and immunoregulatory properties 11-15. Acrabose, miglitol, voglibose, and deoxynojirimycin have clinically been used to restrict the α-glucosidase activity 16. Considering the side effects and absorption problems associated with these drugs, new scaffolds should be synthesized and evaluated by medicinal chemists to extend the library of compounds 17-25. Pyrazoles are common structural motif in numerous drugs 26 and biologically active compounds showing activities such as anti-cancer 27,28 , anti-inflammatory 29 , anti-hypertensive 30 , cannabinoid receptor antagonist 31 , dopaminergic receptor antagonist 32 , and α-glucosidase inhibitors 33. Pyrazoles have been used to synthesize

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Recent synthetic methodologies for pyrazolo[1,5-a]pyrimidine

Cited by 36 publications

References 67 publications

Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazoles

Revisiting the Structure and Chemistry of 3(5)-Substituted Pyrazoles

Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold

An efficient and targeted synthetic approach towards new highly substituted 6-amino-pyrazolo[1,5-a]pyrimidines with α-glucosidase inhibitory activity

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