Synthesis and SAR studies of benzimidazole derivatives as melanin concentrating hormone receptor 1 (MCHR1) antagonists: Focus to detune hERG inhibition

MedChemComm

Volumn 2, Issue 5, 2011, Pages 385-389

  Sasmal, Pradip K ^a   Sasmal, Sanjita ^a   Abbineni, Chandrasekhar ^a   Venkatesham, B ^a   Rao, P Tirumala ^a   Roshaiah, M ^a   Khanna, Ish ^a   Sebastian, V J ^a   Suresh, J ^a   Singh, Manvendra P ^a   Talwar, Rashmi ^a   Shashikumar, Dhanya ^a   Reddy, K Harinder ^a   Frimurer, Thomas M ^b   Rist, Øystein ^b   Elster, Lisbeth ^b   Högberg, Thomas ^b,c  

^a DR REDDY'S LABORATORIES LTD   (India)

^b 7TM Pharma A S   (Denmark)

^c LEO PHARMA A S   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

2 (3 CYANO 4 METHYLPHENYL)ACETIC ACID; 2 CHLOROBENZIMIDAZOLE; 3 CYANO 4 METHYLBENZOIC ACID; 4 HYDROXYBENZALDEHYDE; BENZIMIDAZOLE DERIVATIVE; DIAMINE; MELANIN CONCENTRATING HORMONE RECEPTOR 1; MELANIN CONCENTRATING HORMONE RECEPTOR 1 ANTAGONIST; PIPERIDINE; POTASSIUM CHANNEL HERG; UNCLASSIFIED DRUG;

ALKYLATION; ARTICLE; BROMINATION; CHEMICAL BOND; CHEMICAL MODIFICATION; CHEMICAL STRUCTURE; CHLORINATION; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN; IC 50; ION DISPLACEMENT; PH MEASUREMENT; PRIORITY JOURNAL;

EID: 79959553611     PISSN: 20402503     EISSN: 20402511     Source Type: Journal    
DOI: 10.1039/c1md00015b     Document Type: Article

References (39)

1. J. L. Nahon, Biol., 2006, 329, 623.
2. (a) G. Hervieu, Expert Opin. Ther. Targets, 2003, 7, 495;
3. (b) G. Hervieu, Expert Opin. Ther. Targets, 2006, 10, 211;
4. (c) T. Shimazaki, T. Yoshimizu and S. Chaki, CNS Drugs, 2006, 20, 801;
5. (d) G. Rivera, V. Bocanegra-Garcia, S. Galiano, N. Cirauqui, J. Ceras, S. Perez, I. Aldana and A. Monge, Curr. Med. Chem., 2008, 15, 1025;
6. (e) T. J. Kowalski and T. Sasikumar, BioDrugs, 2007, 21, 311;
7. (f) S. Chaki, T. Funakoshi, S. Hirota-Okuno, M. Nishiguchi, T. Shimazaki, M. Iijima, A. J. Grottick, K. Kanuma, K. Omodera, Y. Sekiguchi, S. Okuyama, T. A. Tran, G. Semple and W. Thomsen, J. Pharmacol. Exp. Ther., 2005, 313, 831.
8. M. Rossi, S. A. Beak, S.-J. Choi, C. J. Small, D. G. A. Morgan, M. A. Ghatei, D. M. Smith and S. R. Bloom, Brain Res., 1999, 846, 164.
9. A. Gomori, A. Ishihara, M. Ito, S. Mashiko, H. Matsushita, M. Yumoto, M. Ito, T. Tanaka, S. Tokita, M. Moriya, H. Iwaasa and A. Kanatani, Am. J. Physiol.: Endocrinol. Metab., 2003, 284, E583-E588.
10. D. S. Ludwig, N. A. Tritos, J. W. Mastaitis, R. Kulkarni, E. Kokkotou, J. Elmquist, B. Lowell, J. S. Flier and E. Maratos-Flier, J. Clin. Invest., 2001, 107, 379.
11. M. Shimada, N. A. Tritos, B. B. Lowell, J. S. Flier and E. Maratos-Flier, Nature, 1998, 396, 670.
12. (a) Y. Chen, C. Hu, C.-K. Hsu, Q. Zhang, C. Bi, M. Asnicar, H. M. Hsiung, N. Fox, L. J. Slieker, D. D. Yang, M. L. Heiman and Y. Shi, Endocrinology, 2002, 143, 2469;
13. (b) D. J. Marsh, D. T. Weingarth, D. E. Novi, H. Y. Chen, M. E. Trumbauer, A. S. Chen, X.-M. Guan, M. M. Jiang, Y. Feng, R. E. Camacho, Z. Shen, E. G. Frazier, H. Yu, J. M. Metzger, S. J. Kuca, L. P. Shearman, S. Gopal-Truter, D. J. MacNeil, A. M. Strack, D. E. MacIntyre, L. H. T. Van der Ploeg and S. Qian, Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 3240.
14. (a) B. Borowsky, M. M. Durkin, K. Ogozalek, M. R. Marzabadi, J. DeLeon, B. Lagu, R. Heurich, H. Lichtabau, Z. Shaposhnik, I. Daniewska, T. P. Blackburn, T. A. Branchek, C. Gerald, P. J. Vaysse and C. Forray, Nat. Med., 2002, 8, 825;
15. (b) S. Takekawa, A. Asami, Y. Ishihara, J. Terauchi, K. Kato, Y. Shimomura, M. Mori, H. Murakoshi, K. Kato, N. Suzuki, O. Nishimura and M. Fujino, Eur. J. Pharmacol., 2002, 438, 129;
16. (c) M. D. McBriar and T. J. Kowalski, Annu. Rep. Med. Chem., 40, 119;
17. (d) H. Dyke and N. C. Ray, Expert Opin. Ther. Pat., 2005, 15, 1303;
18. (e) Y. Shi, Peptides, 2004, 25, 1605;
19. (f) A. Browning, Expert Opin. Ther. Pat., 2004, 14, 313;
20. (g) T. J. Kowalski and M. D. McBriar, Expert Opin. Invest. Drugs, 2004, 13, 1113;
21. (h) J. L. Mendez-Andino and J. A. Wos, Drug Discovery Today, 2007, 12, 972;
22. (i) M. D. McBriar, H. Guzik, S. Shapiro, J. Paruchova, R. Xu, A. Palani, J. W. Clader, K. Cox, W. J. Greenlee, B. E. Hawes, T. J. Kowalski, K. O'Neill, B. D. Spar, B. Weig, D. J. Weston, C. Farley and J. Cook, J. Med. Chem., 2006, 49, 2294;
23. (j) L. L. Rokosz, Expert Opin. Drug Discovery, 2007, 2, 1301;
24. (k) Y. Liu, K. Sprenger, G. Maynard, H. Friedman, L. Anciro, L. Rajachandran and A. Changchit, J. Clin. Pharmacol., 2009, 49, 1101.
25. (a) J. L.Mendez-Andino and J. A. Wos, Drug Discovery Today, 2007, 12, 972;
26. (b) L. L. Rokosz and D. W. Hobbs, Drug News Perspect., 2006, 19, 273.
27. P. K. Sasmal, S. Sasmal, P. T. Rao, B. Venkatesham, M. Roshaiah, C. Abbineni, I. Khanna, V. P. Jadhav, J. Suresh, R. Talwar, S. Muzeeb, J.-M. Receveur, T. M. Frimurer, Ø. Rist, L. Elster and T. Högberg, Bioorg. Med. Chem. Lett., 2010, 20, 5443.
28. For recent reviews on hERG, see: (a) I. Staudacher, P. Schweizer, H. A. Katus and D. Thomas, Curr. Opin. Drug. Discov. Devel., 2010, 13, 23;
29. (b) H. Wulff, N. A. Castle and L. A. Pardo, Nat. Rev. Drug Discovery, 2009, 8, 982;
30. (c) C. E. Pollard, J. P. Valentin and T. G. Hammond, Br. J. Pharmacol., 2008, 154, 1538;
31. (d) K. Finlayson, H. J. Witchel, J. McCulloch and J. Sharkey, Eur. J. Pharmacol., 2004, 500, 129.
32. (a) U. Zachariae, F. Giordanetto and A. G. Leach, J. Med. Chem., 2009, 52, 4266;
33. (b) C. Jamieson, E. M. Moir, Z. Rankovic and G. Wishart, J. Med. Chem., 2006, 49, 5029.
34. J. M. Goss and S. E. Schaus, J. Org. Chem., 2008, 73, 7651.
35. D. Kikuchi, S. S. Sakaguchi and Y. Ishii, J. Org. Chem., 1998, 63, 6023.
36. S. M. Newman and P. F. Beal, J. Am. Chem. Soc., 1950, 72, 5163.
37. 4. Concentration and purification of the crude over silica gel (100-200 mesh) using 10% ethyl acetate in petroleum ether as eluent afforded compound 18a (717 mg, 60% yield) as a viscous liquid.
38. H. Zhang, Q. Cai and D. Ma, J. Org. Chem., 2005, 70, 5164.
39. HEK293 cells stably expressing hERG potassium channels were voltage clamped using automated Port-A-Patch electrophysiology system. Test items were dissolved in DMSO and diluted with external recording buffer. Cells were exposed to test concentration for approximately 5 min or till a steady state block was reached at 20-35 °C. Each cell acted as its own control. Cisapride (1 μM) was used as an internal positive control to confirm the sensitivity of the test system to hERG inhibition. The extent of inhibition of channel was expressed as a percentage of the control response (minus the test compound).