Synthesis and biological evaluation of novel imidazopyrimidin‐3‐amines as anticancer agents

Abstract

Groebke-Blackburn-Bienayme reaction has been utilized for the synthesis of new imidazo[1,2-a]pyrimidine derivatives as novel anticancer agents. The cytotoxic activities of compounds were evaluated against human cancer cell lines including MCF-7, T-47D, and MDA-MB-231, compared with etoposide as the standard drug. Among the tested compounds, hydroxy- and/or methoxy-phenyl derivatives (6a-c and 6k) with IC values of 6.72-14.36 μm were more potent than etoposide against all cell lines. The acridine orange/ethidium bromide double staining and DNA fragmentation studies demonstrated that the cytotoxic effect of 3-hydroxy-4-methoxyphenyl derivative 6c is associated with apoptosis in cancer cells.

The Groebke‐Blackburn‐Bienaymé Reaction

“…B: the proposed mechanism, driven by the stability of the product and properties of the initial starting material, such as aromaticity of the ring, bulkiness of substituents and solvent. No solvent [19,60,71,79,81,83,85,90,92,93,101,105,111,112,127,133,140,147,148,161,172,192,195] 23 Water [46,76] 2 Toluene [43,49,52,70,95,109,144,145,158,159,163,164,171,186,189,190] 17 DMSO [33,36] 2 EtOH [57,84,89,104,113,115,116,<...>…”

Copper-catalyzed synthesis of diarylamines using p-toluene sulfonamides and benzhydrol derivatives under homogeneous borrowing hydrogen conditions

“…Copper salts were dried overnight at 120 • C. Benzhydrol derivatives were prepared according to previously reported procedures [31]. 1 H NMR and 13 C NMR spectra were recorded on BrukerAvIII HD-500 MHz using TMS as an internal standard.…”

“…Amines play an important role in biological [1,2], pharmacological [3] and agricultural [4] activities. Hence the synthesis of substituted amines (the structural active motif of several drugs such as cetirizine [5], sertraline [6], rasagiline [7] and rivastigmine [8]) has been attracting increasing attention.…”

“…• C[33] 1. H NMR (500 MHz, CDCl 3 ): δ 7.62 (d, J = 8.2 Hz, 2H), 7.32 -7.37 (m, 1H), 7.20 -7.25 (m, 4H), 7.13 -7.18 (m, 4H), 7.07 (dd, J = 7.0, 2.2 Hz, 2H), 5.92 (d, J = 7.2 Hz, 1H), 5.31 (d, J = 7.2 Hz, 1H), 2.38 (s, 3H).…”

“…N-((4-fluorophenyl)(phenyl)methyl)-4methylbenzenesulfonamide (3f ) White solid; yield: 353 mg (95%); mp 123-124 • C [36]. 1 H NMR (500 MHz, CDCl 3 ): δ 7.55 (d, J = 8.3 Hz, 2H), 7.17 -7.21 (m, 3H), 7.02 -7.07 (m, 4H), 6.92 -6.96 (m, 4H), 5.54 (d, J = 7.1 Hz, 1H), 5.16 (d, J = 7.0 Hz, 1H), 2.39 (s, 3H).N-((4-methoxyphenyl)(phenyl)methyl)-4methylbenzenesulfonamide (3g)White solid; yield: 326 mg (85%); mp 126-128 • C[37].4-methyl-N-((4-nitrophenyl)(phenyl)methyl) benzenesulfonamide (3h)Light yellow solid; yield: 367 mg (92%); mp 125-126 • C[38] 1. H NMR (500 MHz, CDCl 3 ): δ 7.58 (d, J = 8.1 Hz, 2H-Ar), 7.22-7.26 (m, 3H, Ar-H), 7.22-7.16 (m, 4H),7.10-7.04 (m, 4H) 5.55 (d, J = 6.9 Hz, 1H, NCH), 5.01 (d, J = 6.9 Hz, 1H, HN), 2.42 (s, 3H).…”