Fused Imidazopyrazoles: Synthetic Strategies and Medicinal Applications

Abstract

The current review summarizes the known synthetic routes of fused imidazopyrazoles. This review is classified into two main categories based on the type of annulations, for example, annulation of the imidazole ring onto a pyrazole scaffold or annulation of the pyrazole ring onto an imidazole scaffold. Some medicinal applications of imidazopyrazoles are mentioned.

A novel synthetic approach to Pyrazolooxazines. One‐pot synthesis of Pyrazolo[5,1‐c][1,4]oxazine derivatives from 2,2‐dichlorovinylacetophenones

“…Pure products 7 were isolated by silica gel column chromatography (EtOAc:hexane1:4 as eluent). (29), 243 (20), 189 (M + -CHCl 2 , 100), 171 (21), 157 (8), 145 (44), 128 (16), 104 (17), 77 (24), 51 (12)…”

“…The pyrazole core is a highly important scaffold in medicinal chemistry whose fusion with other pharmacophoric heterocyclic systems has revealed to be of great interest in the search for outstanding biological activities. Numerous comprehensive reviews have been recently devoted to this subject, for example, pyrazolopyrimidines [1][2][3], pyrazolopyrazines [4], pyrazoloquinazolines [5], pyrazolothiazoles [6], among others [7][8][9][10][11][12]. On the other hand, abundant studies on biological properties of oxazine derivatives have demonstrated that they are promising agents to develop drugs with sedative, analgesic, anticonvulsant, antipyretic, antimicrobial, antitubercular, antimalarial, antioxidant, and anticancer activities [13].…”

“…4.10-4.14 (m, 2H), 4.23-4.26 (m, 2H), 4.86 (s, 2H), 6.11 (s, 1H), 7.01-7.05 (m, 2H), 7.40 (d, 1H, J = 3.9 2 ), 100.62 (CH), 126.44 (CH), 129.14 (CH), 130.16 (C), 131.39 (CH), 135.63 (C), 136.31 (C), 137.31 (C), 151.35 (C=N); MS (EI) m/z (%): 228 (M + , 100), 197(11), 171(19), 170(13), 145(23), 130(12), 115(8), 98 (4), 77 (6); Anal.…”

Synthesis and Crystal Structures of 4,5-Dihydroimidazo[1,5-b]pyrazol-6-ones

“…1,2 Imidazopyrazoles have been recognized as substances of significant chemical, biological and medicinal interest. 3,4 By far, the most well-known compounds are those pertaining to the imidazo [1,2-b]pyrazole family, which have been described as possessing noteworthy anticancer, [4][5][6] antibacterial, 7,8 and anti-inflammatory 9,10 properties, among others. 5-Aminopyrazoles, the synthetic methods for which have been extensively reviewed, 11 are the main preparative intermediates for imidazo[1,2-b]pyrazoles.…”

“…32,33,36,40,41 However, synthetic methodology for obtaining imidazo [1,5-b]pyrazole derivatives is notably lacking, and very little is known about these compounds. 3,4 Only a few individual examples having this uncommon ring fusion have been previously prepared; for example, by cyclodehydration of substituted pyrazolylmethylacetamides leading to 2,3-dihydroimidazo [1,5-b] derivatives related to cyclized histamine, 43 preparation of 2,3-dihydro-1H-imidazo [1,5-b]pyrazole-4,6(3aH,5H)-dione from 1-(benzylideneamino)-5-(2-hydroxyethyl)hydantoin, 44 and the synthesis of hexahydro-4,4-dimethyl-1,3a-diaryl-6-oxo-1H-imidazo [1,5-b]pyrazole-3-carbonitriles from -aminoisobutyrophenone phenyl hydrazones. 45 Concerning imidazopyrazolones, studies on the synthesis, properties and usefulness of substances exhibiting [1,2-b], [46][47][48][49][50] [4,5-c], 51,52 and [3,4-b] 45 ring systems have been successful.…”