Recent Developments in the Synthesis of Indole‐Pyrazole Hybrids

Abstract

Indole and pyrazole are two important scaffolds in the field of medicinal chemistry. Compounds bearing indole and/or pyrazole moiety have been extensively investigated for a wide range of biological applications. Of them, compounds containing both indole and pyrazole moieties (also termed as indole‐pyrazole hybrids) are of particular interest since synergistic pharmacological activities may be gained comparing to those with each individual pharmacophore. Indole‐pyrazole hybrids can be classified into two general classes of direct‐linked hybrids and spacer‐linked hybrids. For each class, it can be sub‐divided into indole‐C2 pyrazole hybrids, indole‐C3 pyrazole hybrids and indole‐C4/5/6/7 pyrazole hybrids based on the substitution position of pyrazole on the indole moiety. Many types of indole‐pyrazole hybrids have been reported with good antimicrobial, anticancer, antitumor, anti‐inflammatory, anti‐oxidant activities etc. However, no papers have been noted to comprehensively summarize the chemical synthesis of these important indole‐pyrazole hybrids as bioactive compounds except for a few reviews focusing on the synthesis of each individual indole‐ and pyrazole‐containing derivatives. Thus, we here present a comprehensive and updated review focusing on the progress of chemical synthesis of all types of indole‐pyrazole hybrids in order to provide a better understanding of the indole‐pyrazole hybrids to researchers in the fields of synthetic chemistry and to facilitating drug development.

Asymmetric Organocatalytic Mannich Reaction in the Synthesis of Hybrid Isoindolinone-Pyrazole and Isoindolinone-Aminal from Functionalized α-Amidosulfone

“…In order to confirm this hypothesis and overcome the racemization issue, our attention focused on the use of hydrazine, which should react selectively with acetylacetone to provide pyrazole ring, [ 24 ] a moiety also found in a very large number of bioactive compounds, [ 10 , 11 , 12 ] often combined with other heterocycles [ 12 ]. Therefore, the enantioenriched acyclic product 2 was treated with hydrazine under the conditions shown in Scheme 2 , leading nicely to the pyrazole derivative 4 in a very high yield.…”

“…The value of some classes of compounds is often associated with the structural diversity and the presence of different functionalities and moieties. This feature is relevant in classes of heterocycles such as isoindolinones [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ] and pyrazoles [ 10 , 11 , 12 ], whose biological activities are tuned by the linking of additional nitrogen-containing substituents or heterocyclic groups such as piperazines, piperidines, and so on ( Figure 1 ).…”

Antimicrobial Activity of N‐Substituted Derivatives of 5‐Chloro‐2,3‐ Diphenyl Indole

“…Several recent publications have reported the biological activity of organic molecules with an indole moiety in their chemical compositions. [1][2][3][4][5][6][7][8] Indoles are considered to play a significant role in drug discovery in almost all evaluations because of their extensive and varied biological actions. As a result, a lot of study has been done over the past few decades to synthesize and investigate the different medicinal possibilities of this moiety.…”

“…Several recent publications have reported the biological activity of organic molecules with an indole moiety in their chemical compositions [1–8] . Indoles are considered to play a significant role in drug discovery in almost all evaluations because of their extensive and varied biological actions.…”