Approaches towards the synthesis of 5-aminopyrazoles

Abstract

SummaryThe biological and medicinal properties of 5-aminopyrazoles have prompted enormous research aimed at developing synthetic routes to these heterocyles. This review focuses on the biological properties associated with this system. Various synthetic methods developed up to 2010 for these compounds are described, particularly those that involve the reactions of β-ketonitriles, malononitrile, alkylidenemalononitriles and their derivatives with hydrazines, as well as some novel miscellaneous methods.

N,N-Dialkyl-N′-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. Part X. The First Pyrazolo[1,5-b][1,2,4,6]thiatriazine Derivatives and their Unusual Reactions with Acylating Agents

“…Interestingly, as there are very few examples of naturally occurring pyrazoles, probably due to the difficulty in the construction of N-N bonds by living organisms, the availability of pyrazolecontaining compounds is predicated upon synthetic methods. [4,5] In addition, pyrazole rings are known to be relatively stable to metabolism compared with other five-membered ring heteroaromatic compounds [6] and unlike isoxazoles and isothiazoles, this ring has not been shown to undergo reductive metabolism, [7] so it is unsurprising that pyrazoles are a common motif in drug molecules.…”

“…We recently reported [8] that the reaction between N,N-dialkyl N 0 -chlorosulfonyl chloroformamidines 1 and N-unsubstituted pyrazol-3-ones produced two previously unknown pyrazolofused oxathiadiazine ring systems, along with, in minor proportion(s), one or two isomers of the rare pyrazolo [1,2-b] [1,2,3,5] thiatriazole ring system. The four possible regioisomeric products from this reaction apparently arise from the numerous tautomeric forms adopted by N-unsubstituted pyrazol-3-ones.…”

Synthesis and Biological Activities of Novel 1,7-dihydropyrazolo[3,4-d]imidazo[1,2-f]pyrimidines

“…The 5-amino-4-cyano-N 1 -phenylpyrazole 2, used as a starting material, was prepared in two steps following a similar method reported by Petrie and al [12][13][14]. The first step involves acid catalyzed condensation of orthoester with malonate to form ethoxymethylene malononitrile 1.…”

QSAR Study of Anthra[1,9-cd]pyrazol-6(2H)-one Derivatives as Potential Anticancer Agents Using Statistical Methods

“…Moreover, this structure is particularly rare in nature. Pyrazole derivatives, several members of the pyrazoles class, have shown good pharmacological effects or have the potential biological activities, such as anti-inflammatory [9], antiviral [10], antimicrobial [11], anticonvulsant [12], antitumor [13], fungicidal activities [14], and antihistaminic [15] activities.…”