Organic Letters
Letter
(7) (a) Decker, M. J. Med. Chem. 2006, 49, 5411. (b) Decker, M.;
Krauth, F.; Lehmann, J. Bioorg. Med. Chem. 2006, 14, 1966. (c) Decker,
M. Eur. J. Med. Chem. 2005, 40, 305.
(8) Chern, J. W.; Tao, P. L.; Yen, M. H.; Lu, G. Y.; Shiau, C. Y.; Lai,
Y. J.; Chien, S. L.; Chan, C. H. J. Med. Chem. 1993, 36, 2196.
(9) Perchellet, J.-P. H.; Waters, A. M.; Perchellet, E. M.;
Naganaboina, V. K.; Chandra, K. L.; Desper, J.; Rayat, S. Anticancer
Res. 2011, 31, 2083.
mediated cascade intramolecular cyclization. The reaction
conditions are compatible with most of the tested functional
groups and effectively afford the desired N-fused heterocycles 5
in moderate to excellent yields. Since electrophilic aromatic
substitution is a critical step in the formation of 5, the
cyclization outcome and its yields seem to be dependent on the
electronic nature of the substituents and their respective
positioning on the heteroenyne-allene 3 scaffold. Furthermore,
this method offers a promising new way to construct different
types of ring fusions to the quinazolinimine scaffold by varying
the nature of the aryl group on the N3 of the carbodiimide.
These investigations will be reported in due course.
(10) Szczepankiewicz, W.; Suwinski, J. Chem. Heterocycl. Compd.
2001, 36, 809.
(11) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003,
103, 893.
(12) (a) Koyama, N.; Inoue, Y.; Sekine, M.; Hayakawa, Y.; Homma,
H.; Oinmura, S.; Tomoda, H. Org. Lett. 2008, 10, 5273. (b) Takeuchi,
Y.; Harayama, T. Trends Heterocycl. Chem. 2001, 7, 65. (c) Cagir, A.;
Jones, S. H.; Gao, R.; Eisenhauer, B. M.; Hecht, S. M. J. Am. Chem. Soc.
2003, 125, 13628. (d) Zheng, X.-y.; Zhang, Z.-j.; Chou, G.-x.; Wu, T.;
Cheng, X.-m.; Wang, C.-h.; Wang, Z.-t. Arch. Pharm. Res. 2009, 32,
1245.
(13) (a) Prashanth, M. K.; Revanasiddappa, H. D. Med. Chem. Res.
2013, 22, 2665. (b) Gor, D. G.; Patel, P. A.; Patel, P. S. Int. J. Pharm.
Res. Scholars 2012, 1, 12.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures, optimization of reaction conditions
1
table, H and 13C NMR spectra of all new compounds; X-ray
data and cif files of 5a′ and 5k′. This material is available free of
(14) (a) Hirai, S.; Kikuchi, H.; Kim, H.-S.; Begum, K.; Wataya, Y.;
Tasaka, H.; Miyazawa, Y.; Yamamoto, K.; Oshima, Y. J. Med. Chem.
2003, 46, 4351. (b) Zhu, S.; Meng, L.; Zhang, Q.; Wei, L. Bioorg. Med.
Chem. Lett. 2006, 16, 1854.
AUTHOR INFORMATION
■
Corresponding Author
(15) (a) Ilangovan, P.; Ganguly, S.; Pandi, V. J. Pharm. Res. 2010, 3,
703. (b) Bhandari, S. V.; Deshmane, B. J.; Dangare, S. C.; Gore, S. T.;
Raparti, V. T.; Khachane, C. V.; Sarkate, A. P. Pharmacologyonline
2008, 604.
Author Contributions
All authors have approved the final version of the manuscript.
Notes
(16) (a) Bhattacharya, S.; Ahmad, Y.; Chaudhary, M. Pharmacolo-
gyonline 2012, 2, 66. (b) Dhani, R. Int. J. Appl. Biol. Pharm. Technol.
2012, 3, 381. (c) Ramesh, P.; Srinivasulu, D.; Rao, D. S.; Kumar, K. H.;
Rajasekhar, D.; Raju, C. N. Pharm. Lett. 2012, 4, 1344.
(17) (a) Hour, M.-J.; Lee, K.-T.; Wu, Y.-C.; Wu, C.-Y.; You, B.-J.;
Chen, T.-L.; Lee, H.-Z. Arch. Toxicol. 2012, 87, 835. (b) Hour, M.-J.;
Tsai, S.-C.; Wu, H.-C.; Lin, M.-W.; Chung, J.-G.; Wu, J.-B.; Chiang, J.-
H.; Tsuzuki, M.; Yang, J.-S. Int. J. Oncol. 2012, 41, 1513. (c) Murahari,
M. S.; Prakash, R. S. J.; Kar, S. S.; Kumar, T. G.; Raj, P. V.; Raju, D. S.
J. Pharm. Res. 2012, 5, 2743.
(18) (a) Hess, H. J.; Cronin, T. H.; Scriabine, A. J. Med. Chem. 1968,
11, 130. (b) Chen, Z.; Hu, G.; Li, D.; Chen, J.; Li, Y.; Zhou, H.; Xie, Y.
Bioorg. Med. Chem. 2009, 17, 2351. (c) Kubota, H.; Kakefuda, A.;
Watanabe, T.; Ishii, N.; Wada, K.; Masuda, N.; Sakamoto, S.;
Tsukamoto, S.-I. J. Med. Chem. 2003, 46, 4728.
(19) (a) Aly, M. M.; Mohamed, Y. A.; El-Bayouki, K. A. M.;
Basyouni, W. M.; Abbas, S. Y. Eur. J. Med. Chem. 2010, 45, 3365.
(b) Dhani, R. Int. J. Anal., Pharm. Biomed. Sci. 2012, 1, 30.
(20) (a) Wakimoto, T.; Murayama, R.; Nagayama, K.; Okuda, Y.;
Nakada, H. Appl. Surf. Sci. 1997, 113/114, 698. (b) Tsai, J.-Y.; Yeager,
W.; Brooks, J.; Beers, S.; Kottas, G. S.; Barron, E.; Kwong, R. U.S.
Patent 20100148663, 2010.
(21) (a) Patel, D. R.; Patel, K. C. Fibers Polym. 2011, 12, 741.
(b) Zhang, J.; Lakowicz, J. R. J. Phys. Chem. B 2005, 109, 8701.
(22) (a) Qiu, G.; Liu, G.; Pu, S.; Wu, J. Chem. Commun. 2012, 48,
2903. (b) Naganaboina, V. K.; Chandra, K. L.; Desper, J.; Rayat, S.
Org. Lett. 2011, 13, 3718. (c) Linsenmeier, A. M.; Williams, C. M.;
Brase, S. J. Org. Chem. 2011, 76, 9127. (d) Mandadapu, A. K.; Dathi,
M. D.; Arigela, R. K.; Kundu, B. Tetrahedron 2012, 68, 8207. (e) Read,
M. L.; Gundersen, L.-L. J. Org. Chem. 2013, 78, 1311. (f) Tobisu, M.;
Koh, K.; Furukawa, T.; Chatani, N. Angew. Chem., Int. Ed. 2012, 51,
11363. (g) Wu, Y.; Wong, S. M.; Mao, F.; Chan, T. L.; Kwong, F. Y.
Org. Lett. 2012, 14, 5306. (h) Chern, J. W.; Tao, P. L.; Yen, M. H.; Lu,
G. Y.; Shiau, C. Y.; Lai, Y. J.; Chien, S. L.; Chan, C. H. J. Med. Chem.
1993, 36, 2196. (i) Wang, Y.-F.; Zhang, F.-L.; Chiba, S. Org. Lett.
2013, 15, 2842. (j) Durgareddy, G. A. N. K.; Ravikumar, R.; Ravi, S.;
Adapa, S. R. J. Chem. Sci. 2013, 125, 175. (k) Vovk, M. B. Russ. J. Org.
Chem. 2007, 43, 312.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors acknowledge Dr. Leila Maurmann at Kansas State
University for valuable help and discussions on the NMR
structural characterization of the heterocycles. S.R. is grateful
for the Senior Research Grant from the Indiana Academy of
Sciences for partial support of this work.
REFERENCES
■
(1) (a) Matsumoto, K.; Choshi, T.; Hourai, M.; Zamami, Y.; Sasaki,
K.; Abe, T.; Ishikura, M.; Hatae, N.; Iwamura, T.; Tohyama, S.;
Nobuhiro, J.; Hibino, S. Bioorg. Med. Chem. Lett. 2012, 22, 4762.
(b) Sun, Q.; Shen, Y.-H.; Tian, J.-M.; Tang, J.; Su, J.; Liu, R.-H.; Li, H.-
L.; Xu, X.-K.; Zhang, W.-D. Chem. Biodiversity 2009, 6, 1751.
(c) Lyakhova, E. G.; Kolesnikova, S. A.; Kalinovsky, A. I.;
Afiyatullov, S. S.; Dyshlovoy, S. A.; Krasokhin, V. B.; Minh, C. V.;
Stonik, V. A. Tetrahedron Lett. 2012, 53, 6119. (d) Berkov, S.;
Cuadrado, M.; Osorio, E.; Viladomat, F.; Codina, C.; Bastida, J. Planta
Med. 2009, 75, 1351. (e) Abdel-Halim, O. B.; Morikawa, T.; Ando, S.;
Matsuda, H.; Yoshikawa, M. J. Nat. Prod. 2004, 67, 1119.
(2) (a) Park, G. Y.; Wilson, J. J.; Song, Y.; Lippard, S. J. Proc. Natl.
Acad. Sci. U.S.A. 2012, 109, 11987. (b) Rajagopalan, R.; Lin, T.-S.;
Karwa, A. S.; Poreddy, A. R.; Asmelash, B.; Dorshow, R. B. ACS Med.
Chem. Lett. 2012, 3, 284.
(3) Ishikawa, T. Med. Res. Rev. 2001, 21, 61.
(4) Nakamura, M.; Aoyama, A.; Salim, M. T. A.; Okamoto, M.; Baba,
M.; Miyachi, H.; Hashimoto, Y.; Aoyama, H. Bioorg. Med. Chem. Lett.
2010, 18, 2402.
(5) Miao, F.; Yang, X.-J.; Ma, Y.-N.; Zheng, F.; Song, X.-P.; Zhou, L.
Chem. Pharm. Bull. 2012, 60, 1508.
(6) Dubost, E.; Dumas, N.; Fossey, C.; Magnelli, R.; Butt-Gueulle, S.;
Ballandonne, C.; Caignard, D. H.; Dulin, F.; Sopkova de-Oliveira-
Santos, J.; Millet, P.; Charnay, Y.; Rault, S.; Cailly, T.; Fabis, F. J. Med.
Chem. 2012, 55, 9693.
(23) Demeunynck, M.; Baussanne, I. Curr. Med. Chem. 2013, 20, 794.
1497
dx.doi.org/10.1021/ol500314x | Org. Lett. 2014, 16, 1494−1497