Open Access Published by De Gruyter July 22, 2017

An efficient approach to the synthesis of coumarin-fused dihydropyridinones

Loghman Firoozpour, Hamideh Nikookar, Setareh Moghimi, Mohammad Mahdavi, Ali Asadipour, Parviz Rashidi Ranjbar and Alireza Foroumadi

Abstract

3,4-Dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione derivatives were efficiently prepared by the reaction of 4-hydroxycoumarin, ammonia, aromatic aldehyde and Meldrum’s acid in refluxing 1-propanol.

Introduction

The development of high yielding, efficient and reliable strategies is needed to access the manifolds of polycyclic reaction products for biological evaluation [1], [2]. Multi-component reaction (MCR) methodology is highly preferred over other synthetic methods, successfully providing a short synthetic pathway to desired products. The capability of this valuable synthetic approach has been considered by pharmaceutical companies for the large-scale synthesis of drugs [3], [4], [5].

In the field of medicinal chemistry, coumarin constitutes an exceptional structural framework in bioactive compounds [6], [7], [8], [9], [10], [11], [12], [13] and an impressive number of synthetic methods [14], [15], [16], [17], [18], [19], [20], [21] have been reported to enhance the collection of coumarin-containing molecules [22], [23], [24], [25]. Fused bicyclic chromenes are of considerable interest. Such compounds are anti-cancer [26], glucocorticoid receptor agonist [27], anti-bacterial [28], anti-histaminic [29] and anti-myopic agents [30]. Following our focus on the synthesis of heterocyclic compounds [31], [32], [33], [34], [35], [36], [37], in the present paper, we report the convenient, four-component construction of 4-aryl-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-diones, starting from 4-hydroxycoumarin, ammonia, aldehyde and Meldrum’s acid.

Results and discussion

The synthetic pathway is outlined in Scheme 1. In a model reaction, 4-hydroxycoumarin (1), aqueous ammonia (2), benzaldehyde (3a) and Meldrum’s acid (4) were allowed to react in 1-propanol to furnish product 5a. Under optimized conditions the reaction is conducted in boiling 1-propanol in the presence of five equivalents of ammonia. With ammonium acetate as a nitrogen source under otherwise similar conditions the yield of 5a was only 45%, even after prolonged reflux. Under the optimized reaction conditions, different aromatic aldehydes were evaluated to examine the generality of the cyclization reaction. In the presence of electron-donating and electron-withdrawing substituents at the 2-, 3- and 4-positions of the phenyl ring the target compounds were obtained in good yields.

Scheme 1

Scheme 1

In the proposed mechanism (Scheme 2), the amination reaction of 1 leads to generation of 4-aminocoumarin 6 which then undergoes a Michael-type addition reaction to the intermediate product 7. Compound 7 is a product of a Knoevenagel condensation reaction between the aromatic aldehyde and Meldrum’s acid. The intramolecular cyclization process after the loss of acetone and CO2 from the intermediate product 8 results in the formation of the final product 5 (Scheme 2). To confirm the reaction mechanism, the intermediate products 6 and 7 were prepared separately [38]. As expected, their reaction furnished the product 5.

Scheme 2

Scheme 2

Conclusions

An efficient and straightforward method was developed for the synthesis of 3,4-dihydro-1H-chromeno[4,3-b]pyridine-2,5-diones 5. The method involves a simple, one-pot, four-component reaction.

Experimental

1H nuclear magnetic resonance (NMR) (500 MHz) and 13C NMR (125 MHz) spectra were obtained in DMSO-d6. Infrared spectroscopy (IR) spectra were recorded in KBr pellets. Additional general information is described in reference [16].

General procedure for the synthesis of 3,4-dihydro-1H-chromeno[4,3-b]pyridine-2,5-diones 5a–i

A solution of 4-hydroxycoumarin (1 equiv.) and ammonia (30%, 5 equiv.) in 1-propanol (10 mL) was heated under reflux for 1 h, after which time, Meldrum’s acid (1 equiv.) and aromatic aldehyde (1.1 equiv.) were added and the mixture was heated under reflux for an additional 12 h. Then the mixture was concentrated under a reduced pressure and the residue was purified on a silica gel column eluting with petroleum ether/ethyl acetate, 8:2.

4-Phenyl-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5a)

Yield 68% of a pale yellow powder; mp 230°C (dec.); IR: 3287, 3038, 2905, 1715, 1678, 1625, 1517, 1458, 1365, 1278, 1196, 1160, 1002, 753 cm−1; 1H NMR: δ 3.03 (d, 1H, J=16.5 Hz), 3.32 (dd, 1H, J=16.5, 7.0 Hz), 4.59 (d, 1H, J=7.0 Hz), 7.20–7.35 (m, 4H), 7.36–7.38 (m, 2H), 7.40 (d, 1H, J=8.5 Hz), 7.61 (t, 1H, J=8.0 Hz), 7.68 (d, 1H, J=8.0 Hz), 8.86 (s, NH); 13C NMR: δ 35.4, 37.8, 113.0, 116.7, 123.0, 124.1, 126.4, 126.9, 128.6, 132.3 (2C), 141.2, 145.4 (2C), 152.6, 170.1. Anal. Calcd for C18H13NO3: C, 74.22; H, 4.50; N, 4.81. Found: C, 74.51; H, 4.32; N, 4.59.

4-(3-Hydroxyphenyl)-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5b)

Yield 62% of a pale yellow powder; mp 230°C; IR: 3239, 1672, 1627, 1580, 1515, 1458, 1367, 1297, 764 cm−1; 1H NMR: δ 2.63 (d, 1H, J=16.0 Hz), 3.22 (dd, 1H, J=16.0, 8.0 Hz), 4.29 (d, 1H, J=8.0 Hz), 6.60 (s, 1H), 6.62 (d, 1H, J=8.0 Hz), 6.66 (d, 1H, J=7.5 Hz), 7.09–7.11 (m, 2H), 7.41 (t, 1H, J=7.5 Hz), 7.45 (d, 1H, J=8.2 Hz), 7.68 (t, 1H, J=7.5 Hz), 8.27 (d, 1H, J=8.2 Hz), 9.44 (brs, NH); 13C NMR: δ 35.4, 37.9, 103.5, 113.2, 116.8, 117.1, 122.9, 123.1, 124.2, 129.7, 132.0, 132.3, 142.6, 145.3, 152.6, 157.6, 160.1, 170.2. Anal. Calcd for C18H13NO4: C, 70.35; H, 4.26; N, 4.56. Found: C, 70.52; H, 4.03; N, 4.33.

4-(2-Methoxyphenyl)-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5c)

Yield 64% of a pale yellow powder; mp 254°C; IR: 3254, 2963, 1725, 1633, 1517, 1490, 1245, 1196, 754 cm−1; 1H NMR: δ 2.53 (d, 1H, J=16.1 Hz), 3.17 (dd, 1H, J=16.1, 8.5 Hz), 3.84 (s, 3H), 4.58 (d, 1H, J=8.5 Hz), 6.80 (t, 1H, J=7.5 Hz), 6.86 (d, 1H, J=7.5 Hz), 7.03 (d, 1H, J=8.5 Hz), 7.23 (t, 1H, J=7.5 Hz), 7.42–7.44 (m, 2H), 7.68 (t, 1H, J=8.2 Hz), 8.26 (d, 1H, J=8.5 Hz), 10.89 (s, NH); 13C NMR: δ 30.8, 36.4, 55.2, 102.2, 111.2, 113.0, 116.7, 120.2, 123.0, 124.1, 126.6, 128.0, 128.3, 132.3, 146.2, 152.7, 156.5, 159.9, 170.1. Anal. Calcd for C19H15NO4: C, 71.02; H, 4.71; N, 4.36. Found: C, 70.88; H, 4.93; N, 4.14.

4-(p-Tolyl)-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5d)

Yield 71% of a pale yellow powder; mp 226°C; IR: 3233, 1727, 1691, 1570, 1459, 1365, 1317, 1293, 1195, 756 cm−1; 1H NMR: δ 2.25 (s, 3H), 2.63 (d, 1H, J=16.5 Hz), 3.22 (dd, 1H, J=16.5, 7.2 Hz), 4.33 (d, 1H, J=7.2 Hz), 7.09–7.11 (m, 4H), 7.40 (t, 1H, J=7.5 Hz), 7.44 (d, 1H, J=8.2 Hz), 7.67 (t, 1H, J=7.5 Hz), 8.25 (d, 1H, J=7.5 Hz), 10.93 (s, NH); 13C NMR: δ 20.4, 35.1, 37.9, 103.6, 113.0, 116.7, 123.0, 124.1, 126.3, 129.2, 132.3, 136.0, 138.2, 145.2, 152.6, 160.1, 170.2. Anal. Calcd for C19H15NO3: C, 74.74; H, 4.95; N, 4.59. Found: C, 74.59; H, 5.10; N, 4.40.

4-(4-Fluorophenyl)-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5e)

Yield 70% of a pale yellow powder; mp 208°C; IR: 3393, 3135, 1718, 1688, 1629, 1566, 1456, 1368, 768 cm−1; 1H NMR: δ 2.67 (d, 1H, J=16.3 Hz), 3.26 (dd, 1H, J=16.3, 7.5 Hz), 4.40 (d, 1H, J=7.5 Hz), 7.13 (t, 2H, J=8.5 Hz), 7.27 (t, 2H, J=6.5 Hz), 7.42 (t, 1H, J=7.5 Hz), 7.45 (d, 1H, J=8.5 Hz), 7.68 (t, 1H, J=7.5 Hz), 8.27 (d, 1H, J=7.5 Hz), 11.02 (s, NH); 13C NMR: δ 34.8, 37.9, 103.3, 113.1, 116.7 (d, JC−F=20 Hz), 123.1 (d, JC−F=8 Hz), 124.1, 124.3, 128.4, 128.6, 132.4, 137.4, 145.5, 152.7, 160.2 (d, JC−F=243 Hz), 170.2. Anal. Calcd for C18H12FNO3: C, 69.90; H, 3.91; N, 4.53. Found: C, 69.73; H, 4.09; N, 4.72.

4-(2-Chlorophenyl)-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5f)

Yield 66% yield of a pale yellow powder; mp 244°C; IR: 3243, 1720, 1634, 1569, 1514, 1462, 1363, 1200, 1176, 1002, 762 cm−1; 1H NMR: δ 2.54 (d, 1H, J=16.5 Hz), 3.32 (dd, 1H, J=16.5, 8.2 Hz), 4.71 (d, 1H, J=8.2 Hz), 7.02 (d, 1H, J=7.3 Hz), 7.21 (t, 1H, J=7.5 Hz), 7.29 (t, 1H, J=7.5 Hz), 7.43–7.47 (m, 2H) 7.52 (d, 1H, J=8.2 Hz), 7.70 (t, 1H, J=7.5 Hz), 8.29 (d, 1H, J=8.2 Hz), 11.07 (s, NH); 13C NMR: δ 33.3, 36.4, 101.9, 113.0, 116.9, 123.2, 124.2, 127.2, 127.7, 129.0, 130.0, 132.4, 132.5, 137.6, 146.8, 152.8, 160.0, 169.5. Anal. Calcd for C18H12ClNO3: C, 66.37; H, 3.71; N, 4.30. Found: C, 66.18; H, 3.54; N, 4.51.

4-(4-Bromophenyl)-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5g)

Yield 75% of a pale yellow powder; mp 170°C; IR: 3223, 1721, 1691, 1632, 1515, 1461, 1365, 759 cm−1; 1H NMR: δ 2.64 (d, 1H, J=16.3 Hz), 3.25 (dd, 1H; overlapping with the solvent signal), 4.37 (d, 1H, J=7.5 Hz), 7.19 (d, 2H, J=8.2 Hz), 7.38–7.55 (m, 4H), 7.69 (t, 1H, J=7.5 Hz), 8.26 (d, 1H, J=7.5 Hz), 11.02 (s, NH); 13C NMR: δ 35.0, 37.6, 102.9, 113.0, 116.7, 120.1, 123.1, 128.8, 130.7, 131.7, 132.5, 140.7, 145.7, 152.7, 160.1, 170.1. Anal. Calcd for C18H12BrNO3: C, 58.40; H, 3.27; N, 3.78. Found: C, 58.23; H, 3.06; N, 4.01.

4-(2-Nitrophenyl)-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5h)

Yield 67% of a pale yellow powder; mp 244°C; IR: 3250, 3042, 1718, 1635, 1572, 1460, 1340, 1296, 855, 762 cm−1; 1H NMR: δ 2.68 (d, 1H, J=16.5 Hz), 3.50 (dd, 1H, J=16.5, 8.5 Hz), 4.79 (d, 1H, J=8.5 Hz), 7.34 (d, 1H, J=7.5 Hz), 7.48–7.51 (m, 2H), 7.57 (t, 1H, J=7.2 Hz), 7.65 (t, 1H, J=7.1 Hz), 7.75 (t, 1H, J=7.5 Hz), 8.05 (d, 1H, J=7.5 Hz), 8.36 (d, 1H, J=7.5 Hz), 11.21 (s, NH); 13C NMR: δ 31.9, 37.1, 102.0, 113.0, 117.1, 123.4, 125.0, 127.9, 128.2, 128.9, 132.7, 134.0, 135.4, 146.7, 148.6, 152.8, 160.0, 169.4. Anal. Calcd for C18H12N2O5: C, 64.29; H, 3.60; N, 8.33. Found: C, 64.06; H, 3.47; N, 8.11.

4-(3-Nitrophenyl)-3,4-dihydro-2H-chromeno[4,3-b]pyridine-2,5(1H)-dione (5i)

Yield 74% of a pale yellow powder; mp 244°C; IR: 3277, 3091, 1715, 1678, 1524, 1459, 1349, 1277, 762 cm−1; 1H NMR: δ 2.74 (d, 1H, J=16.3 Hz), 3.32 (dd, 1H, J=16.3, 8.5 Hz), 4.57 (d, 1H, J=8.5 Hz), 7.43 (t, 1H, J=7.5 Hz), 7.46 (d, 1H, J=8.2 Hz), 7.61 (t, 1H, J=8.2 Hz), 7.69–7.70 (m, 3H), 8.11 (s, 1H), 8.28 (d, 1H, J=8.5 Hz), 11.09 (s, NH); 13C NMR: δ 35.2, 37.3, 102.4, 113.0, 116.9, 121.4, 122.1, 123.2, 124.2, 130.3, 132.6, 133.3, 143.6, 145.9, 148.1, 152.8, 160.1, 169.9. Anal. Calcd for C18H12N2O5: C, 64.29; H, 3.60; N, 8.33. Found: C, 64.51; H, 3.37; N, 8.15.

Acknowledgments

This study was funded and supported by Tehran University of Medical Sciences (TUMS); Grant no. 95-02-92-32530, and the Iranian National Science Foundation (INSF).

References

[1] Dömling, A. Recent developments in isocyanide based multicomponent reactions in applied chemistry. Chem. Rev.2006, 106, 17–89. Search in Google Scholar

[2] Akritopoulou-Zanze, I. Isocyanide-based multicomponent reactions in drug discovery. Curr. Opin. Chem. Biol.2008, 12, 324–331. Search in Google Scholar

[3] Dömling, A.; Wang, W.; Wang, K. Chemistry and biology of multicomponent reactions. Chem. Rev.2012, 112, 3083–3135. Search in Google Scholar

[4] Cores, A.; Carbajales, C.; Coelho, A. Multicomponent reactions in antimitotic drug discovery. Curr. Top Med. Chem.2014, 14, 2209–2230. Search in Google Scholar

[5] Weber, L. The application of multi-component reactions in drug discovery. Curr. Med. Chem.2002, 9, 2085–2093. Search in Google Scholar

[6] Zarganes-Tzitzikas, T.; Dömling, A. Modern multicomponent reactions for better drug syntheses. Org. Chem. Front.2014, 1, 834–837. Search in Google Scholar

[7] Medina, F. G.; Marrero, J. G.; Macias-Alonso, M.; Gonzalez, M. C.; Cordova-Guerrero, I.; Garcia, A. G. T.; Osegueda-Robles, S. Coumarin heterocyclic derivatives: chemical synthesis and biological activity. Nat. Prod. Rep.2015, 32, 1472–1507. Search in Google Scholar

[8] Kontoggiorgis, C. A.; Hadjipavlou-Litina, D. J. Synthesis and antiinflammatory activity of coumarin derivatives. J. Med. Chem.2005, 48, 6400–6408. Search in Google Scholar

[9] Gaudino, E. C.; Tagliapietra, S.; Martina, K.; Palmisano, G.; Cravotto, G. Recent advances and perspectives in the synthesis of bioactive coumarins. RCS Adv.2016, 6, 46394–46405. Search in Google Scholar

[10] Yu, D.; Suzuki, M.; Xie, L.; Morris-Natschke, S. L.; Lee, K. H. Recent progress in the development of coumarin derivatives as potent anti-HIV agents. Med. Res. Rev. 2003, 23, 322–345. Search in Google Scholar

[11] Xie, L.; Takeuchi, Y.; Cosentino, L. M.; McPhill, A. T.; Lee, K. H. Anti-AIDS agents. Synthesis and anti-HIV activity of disubstituted (3′R,4′R)-3′,4′-Di-O-(S)-camphanoyl-(+)-cis-khellactone analogues. J. Med. Chem. 2001, 44, 664–671. Search in Google Scholar

[12] Venkata, S. K.; Gurupadayya, B. M.; Chandan, R. S.; Nagesha, D. K.; Vishwanathan, B. A review on chemical profile of coumarins and their therapeutic role in the treatment of cancer. Curr. Drug Deliv. 2016, 13, 186–201. Search in Google Scholar

[13] Thakur, A.; Singla, R.; Jaitak, V. Coumarins as anticancer agents: a review on synthetic strategies, mechanism of action and SAR studies. Eur. J. Med. Chem. 2015, 101, 476–495. Search in Google Scholar

[14] Yetra, S. R.; Roy, T.; Bhunia, A.; Porwal, D.; Biju, A. T. Synthesis of functionalized coumaris and quinolones by NHC-catalyzed annulation of modified enals with heterocyclic C-H acids. J. Org. Chem.2014, 79, 4245–4251. Search in Google Scholar

[15] Dey, A.; Ali, M. A.; Jana, S.; Samanta, S.; Hajra, A. Palladium-catalyzed synthesis of indole fused coumarins via cross-dehydrogenative coupling. Tetrahedron Lett.2017, 58, 313–316. Search in Google Scholar

[16] Sadat-Ebrahimi, S. E.; Katebi, S.; Pirali-Hamedani, M.; Moghimi, S.; Yahya-Meymandi, A.; Mahdavi, M.; Shafiee, A.; Foroumadi, A. Three-component, one-pot synthesis of dihydrochromeno[4,3-b]pyrazolo[4,3-e]pyridines. Heterocycl. Commun. 2016, 22, 247–250. Search in Google Scholar

[17] Gupta, S.; Kushwaha, B.; Srivastava, A.; Prasad Maikhuri, J.; Sankhwar, S. N.; Gupta, G.; Dwivedi, A. K. Design and synthesis of coumarin–glyoxal hybrids for spermicidal and antimicrobial actions: a dual approach to contraception. RCS Adv. 2016, 6, 76288–76297. Search in Google Scholar

[18] Hu, Y.-J.; Jiang, N.; Xie, S.-S.; Li, S.-Y.; Lan, J.-S.; Kong, L. Y.; Wang, X.-B. Iodine-promoted sequential Michael and oxidative dehydrogenation processes: synthesis of trisubstituted methanes containing a coumarin and a chromone ring. Tetrahedron2015, 71, 8026–8032. Search in Google Scholar

[19] Rao, L. C.; Kumar, N. S.; Dileepkumar, V.; Murthy, U. S. N.; Meshram, H. M. “On water” synthesis of highly functionalized 4H-chromenes via carbon–carbon bond formation under microwave irradiation and their antibacterial properties. RSC Adv.2015, 5, 28958–28964. Search in Google Scholar

[20] Ahadi, S.; Zolghadr, M.; Khavasi, H. R.; Bazgir, A. A diastereoselective synthesis of pyrano fused coumarins via organocatalytic three-component reaction. Org. Biomol. Chem.2013, 11, 279–286. Search in Google Scholar

[21] Sashidhara, K. W.; Palnati, G. R.; Singh, R.; Upadhyay, A.; Avula, S. R.; Kumara, A.; Kant, R. Molecular iodine catalysed one-pot synthesis of chromeno[4,3-b]quinolin-6-ones under microwave irradiation. Green Chem.2015, 17, 3766–3770. Search in Google Scholar

[22] Singh, R. P.; Singh, D. An elegant synthesis of 6H-benzofuro-[3,2-c][1]benzopyran-6-ones. Heterocycles1985, 23, 903–907. Search in Google Scholar

[23] Boschetti, E.; Molho, D.; Fontaine, L. Derivatives of 4-hydroxy coumarin. U. S. Patent, 3,574,234; Apr 6, 1971. Search in Google Scholar

[24] Yao, T.; Yue, D.; Larock, R. C. An efficient synthesis of coumestrol and coumestans by iodocyclization and Pd-catalyzed intramolecular lactonization. J. Org. Chem.2005, 70, 9985–9989. Search in Google Scholar

[25] Xu, D.-Q.; Wang, Y.-F.; Zhang, W.; Luo, S.-P.; Zhong, A.-G.; Xia, A.-B.; Xu, Z.-Y. Chiral squaramides as highly enantioselective catalysts for Michael addition reactions of 4-hydroxycoumarins and 4-hydroxypyrone to β,γ-unsaturated α-keto esters. Chem. Eur. J.2010, 16, 4177–4180. Search in Google Scholar

[26] Banerjee, S.; Wang, J.; Pfeffer, S.; Ma, D.; Pfeffer, L. M.; Patil, S. A.; Li, W.; Miller, D. D. Design, synthesis and biological evaluation of novel 5H-chromenopyridines as potential anti-cancer agents. Molecules2015, 20, 17152–17165. Search in Google Scholar

[27] Weinstein, D. S.; Gong, H.; Doweyko, A. M.; Cunningham, M.; Habte, S.; Wang, J. H.; Holloway, D. A.; Burke, C.; Gao, L.; Guarino, V.; et al. Azaxanthene based selective glucocorticoid receptor modulators: design, synthesis, and pharmacological evaluation of (S)-4-(5-(1-((1,3,4-thiadiazol-2-yl)amino)-2-methyl-1-oxopropan-2-yl)-5H-chromeno [2,3-b]pyridin-2-yl)-2-fluoro-N,N-dimethylbenzamide (BMS-776532) and its methylene homologue (BMS-791826). J. Med. Chem. 2011, 54, 7318–7333. Search in Google Scholar

[28] Kolokythas, G.; Pouli, N.; Marakos, P.; Pratsinis, H.; Kletsas, D. Design, synthesis and antiproliferative activity of some new azapyranoxanthenone aminoderivatives. Eur. J. Med. Chem. 2006, 41, 71–79. Search in Google Scholar

[29] Venkati, M.; Krupadanam, G. L. D. Afacile synthesis of ethyl-2-methyl-5-aryl-5H-chromeno[3,4-c]pyridine-1-carboxylate. Synth. Commun. 2001, 31, 2589–2598. Search in Google Scholar

[30] Srivastava, S. K.; Tripathi, R. P.; Ramachandran, R. NAD+-dependent DNA Ligase (Rv3014c) from Mycobacterium tuberculosis. Crystal structure of the adenylation domain and identification of novel inhibitors. J. Biol. Chem. 2005, 280, 30273–30281. Search in Google Scholar

[31] Yahya-Meymandi, A.; Nikookar, H.; Moghimi, S.; Mahdavi, M.; Firoozpour, L.; Asadipour, A.; Rashidi Ranjbar, P.; Foroumadi, A. An efficient four-component reaction for the synthesis of chromeno[4,3-b]quinolone derivatives. J. Iran. Chem. Soc.2017, 14, 771–775. Search in Google Scholar

[32] Alipour, M.; Khoobi, M.; Foroumadi, A.; Nadri, H.; Moradi, A.; Sakhteman, A.; Ghandi, M.; Shafiee, A. Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding acetylcholinesterase inhibitors. Bioorg. Med. Chem.2012, 20, 7214–7222. Search in Google Scholar

[33] Razavi, S. F.; Khoobi, M.; Nadri, H.; Sakhteman, A.; Moradi, A.; Emami, S.; Foroumadi, A.; Shafiee, A. Synthesis and evaluation of 4-substituted coumarins as novel acetylcholinesterase inhibitos. Eur. J. Med. Chem.2013, 64, 252–259. Search in Google Scholar

[34] Asadipour, A.; Alipour, M.; Jafari, M.; Khoobi, M.; Emami, S.; Nadri, H.; Sakhteman, A.; Moradi, A.; Sheibani, V.; Moghadam, F. H.; et al. Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors. Eur. J. Med. Chem.2013, 70, 623–630. Search in Google Scholar

[35] Ghanei-Nasab, S.; Nadri, H.; Moradi, A.; Marjani, A.; Shabani, S.; Firoozpour, L.; Moghimi, S.; Khoobi, M.; Hadizadeh, F.; Foroumadi, A. Synthesis and anti-acetylcholinesterase activity of N-[(indolyl)ethyl)coumarin-yloxy)]alkanamides. J. Chem. Res. 2017, 41, 120–123. Search in Google Scholar

[36] Ghanei-Nasab, S.; Khoobi, M.; Hadizadeh, F.; Marjani, A.; Moradi, A.; Nadri, H.; Emami, S.; Foroumadi, A.; Shafiee, A. Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety. Eur. J. Med. Chem. 2016, 121, 40–46. Search in Google Scholar

[37] Bagheri, S. M.; Khoobi, M.; Nadri, H.; Moradi, A.; Emami, S.; Jalili-Baleh, L.; Jafarpour, F.; Homayouni Moghadam, F.; Foroumadi, A.; Shafiee, A. Synthesis and anticholinergic activity of 4-hydroxycoumarin derivatives containing substituted benzyl-1,2,3-triazole moiety. Chem. Biol. Drug Des. 2015, 86, 1215–1220. Search in Google Scholar

[38] Levin, V. V.; Trifonov, A. L.; Zemtsov, A. A.; Struchkova, M. I.; Arkhipov, D. E.; Dilman, A. D. Difluoromethylene phosphabetaine as an equivalent of difluoromethyl carbanion. Org. Lett. 2014, 16, 6256–6259. Search in Google Scholar

Received: 2017-1-19
Accepted: 2017-6-13
Published Online: 2017-7-22
Published in Print: 2017-8-28

©2017 Walter de Gruyter GmbH, Berlin/Boston

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