Diversity‐Oriented Synthesis of Functionalized Imidazopyridine Analogues with Anti‐Cancer Activity through a Transition‐Metal Free, One‐pot Cascade Reaction

Abstract

A transition-metal free, high yielding and efficient three-component reaction was designed and incorporated into two sequential oxidation and cyclization reaction cascades in one-pot with the assistance of microwave irradiation. A chemical collection of functionalized 3-substituted imidazopyridines was prepared by means of the mild reaction and simple operational procedure. The reaction has a broad tolerance for a variety of substituted carbonyl aldehydes, anilines and 2phenyl-imidazo[1,2-a]pyridines. Screening in several cancer cell lines was conducted. Compound 9 i exhibited good potency against HeLa cell lines and this work validated the feasibility of the methodology for generating bioactive compounds.

A Novel Imidazopyridine Derivative Exerts Anticancer Activity by Inducing Mitochondrial Pathway-Mediated Apoptosis

“…Compound 9i Inhibits Cervical Cancer Cell Viability in a Time-and Concentration-Dependent Manner. Our previous study found that a series of novel imidazopyridine analogues have anticancer activity in various tumor cell lines [6]. We want to further explore the molecular mechanism of the anticancer effect of these compounds.…”

“…Small molecular compound 9i was synthesized by the chemical synthesis lab of IATTI as previously described [ 6 ]. Other regular chemical reagents were purchased from Sigma-Aldrich.…”

“…Imidazopyridines were reported to have anticancer properties in human cancer cell lines U251 (glioma), PC-3 (prostate), K-562 (leukemia), HCT-15 (colon), MCF7 (breast), SK-LU-1 (lung) [4], and LN-405 (glioblastoma) [5]. Based on these prominent anticancer effects of imidazopyridine compounds, we synthesized a series of imidazopyridine derivatives and tested their anticancer activity in various tumor cell lines [6]. In these compounds, compound 9i (4-(8-bromo-3-(3-oxo-3,4-dihydroquinoxalin-2-yl) imidazo [1,2-a] pyridin-2-yl) benzonitrile) had the best anticancer effect on the human cervical cancer cell line HeLa.…”

Visible light-driven highly atom-economical divergent synthesis of substituted fluorenols and cyclopropylcarbaldehydes

“…1 Moreover, it can facilitate the formation of pharmaceutical and bioactive scaffolds 2 and versatile intermediates in organic synthesis 3 and provide access to natural products 4 under sustainable reaction conditions. The construction of these motifs has drawn considerable attention for use in different reactions, including intermolecular–intramolecular cascade cyclization, 5 ring expansion/contraction, 6 transition-metal/metal-free catalysis, 7 and radical chemistry. 8 However, most of these preparative methods involve the multistep synthesis of starting precursors, generation of toxic waste, low atom economy, and harsh reaction conditions, limiting their applicability in synthetic organic chemistry.…”

Use of Imidazo[1,2‐a]pyridine as a Carbonyl Surrogate in a Mannich‐Like, Catalyst Free, One‐Pot Reaction

“…Significant advancement has been made to modify the C‐3 position of imidazo[1,2‐ a ]pyridine using alkylation, thiocyanation, nucleophilic addition,, arylation or alkenylation, fluorination, and acetylation . However, aminomethylation at the C‐3 position of imidazo[1,2‐ a ]pyridine is rare with only two reports in the literature , .…”