Prospective CCR5 small molecule antagonist compound design using a combined mutagenesis/modeling approach

Journal of the American Chemical Society

Volumn 133, Issue 41, 2011, Pages 16477-16485

  Metz, Markus ^a   Bourque, Elyse ^a   Labrecque, Jean ^b   Danthi, Sanjay J ^b   Langille, Jonathan ^b   Harwig, Curtis ^b   Yang, Wen ^b   Darkes, Marilyn C ^b   Lau, Gloria ^b   Santucci, Zefferino ^b   Bridger, Gary J ^b   Schols, Dominique ^c   Fricker, Simon P ^b   Skerlj, Renato T ^a  

^a Department of Medicinal Chemistry ^*  (United States)

^b GENZYME CORPORATION   (United States)

^c REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ALLOSTERIC INHIBITOR; ANTI-VIRAL DRUGS; BINDING MODES; EXTRACELLULAR LOOP 2; IN-VITRO; IN-VITRO EVALUATION; INTERACTION SITE; MEDICINAL CHEMISTRY; PHARMACOPHORES; SMALL MOLECULES; STRUCTURAL REQUIREMENTS;

BINDING ENERGY; COMPUTATIONAL CHEMISTRY; DESIGN; MOLECULAR BIOLOGY; VIRUSES;

BINDING SITES;

4 PHENYLIMIDAZOLIDIN 2 ONE; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; MARAVIROC; POTASSIUM CHANNEL HERG; THIOPHEN 3 YL METHYL UREA; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ANTIVIRAL ACTIVITY; ARTICLE; CYTOTOXICITY; DRUG BINDING SITE; DRUG RECEPTOR BINDING; IN VITRO STUDY; MOLECULAR BIOLOGY; MUTAGENESIS; VIRUS RESISTANCE;

ANTI-HIV AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; ETHER-A-GO-GO POTASSIUM CHANNELS; HIV-1; HUMANS; LEUKOCYTES, MONONUCLEAR; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MOLECULAR WEIGHT; MUTAGENESIS; RECEPTORS, CCR5; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

EID: 80054763142     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja2043722     Document Type: Article

References (52)

1. Kwong, P. D.; Wyatt, R.; Robinson, J.; Sweet, R. W.; Sodroski, J.; Hendrickson, W. A. Nature 1998, 393, 648-659
2. Berger, E. A.; Doms, R. W.; Fenyoe, E.-M.; Korber, B. T. M.; Littman, D. R.; Moore, J. P.; Sattentau, Q. J.; Schuitenmaker, H.; Sodroski, J.; Weiss, R. A. Nature 1998, 391, 240
3. Alkhatib, G.; Berger, E. A. Eur. J. Med. Res. 2007, 12, 375-384
4. Burton, A. Lancet Infect. Dis. 2003, 3, 260
5. De Clercq, E. Curr. Med. Chem. 2001, 8, 1543-1572
6. Perry, C. M. Drugs 2010, 70, 1189-1213
7. Sayana, S.; Khanlou, H. Expert Rev. Anti-Infect. Ther. 2009, 7, 9-19
8. Kromdijk, W.; Hiutema, A. D.; Mulder, J. W. Expert Opin. Pharmacother. 2010, 11, 1215-1223
9. Nishizawa, R.; Nishiyama, T.; Hisaichi, K.; Hirai, K.; Habashita, H.; Takaoka, Y.; Tada, H.; Sagawa, K.; Shibayama, S.; Maeda, K.; Mitsuya, H.; Nakai, H.; Fukushima, D.; Toda, M. Bioorg. Med. Chem. Lett. 2010, 20, 763-766
10. Yang, H.; Lin, X.-F.; Padilla, F.; Gabriel, S. D.; Heilek, G.; Ji, C.; Sankuratri, S.; deRosier, A.; Berry, P.; Rotstein, D. M. Biorg. Med. Chem. Lett. 2009, 19, 209-213
11. Pryde, D. C. Biorg. Med. Chem. Lett. 2009, 19, 1084-1088
12. Barber, C. G.; Blakemore, D. C.; Chiva, J.-Y.; Eastwood, R. L.; Middleton, D. S.; Paradowski, K. A. Bioorg. Med. Chem. Lett. 2009, 19, 1499-1503
13. Duan, M.; Aquino, C.; Ferris, R.; Kazmierski, W. M.; Kenakin, T.; Koble, C.; Wheelan, P.; Watson, C.; Youngman, M. Bioorg. Med. Chem. Lett. 2009, 19, 1610-1613
14. Rotstein, D. M. Bioorg. Med. Chem. Lett. 2009, 19, 5401-5406
15. Lemoine, R. C.; Peterson, A. C.; Setti, L.; Wanner, J.; Jekle, A.; Heilek, G.; deRosier, A.; Ji., C.; Berry, P.; Rotstein, D. Bioorg. Med. Chem. Lett. 2010, 20, 704-708
16. Lemoine, R. C.; Petersen, A. C.; Setti, L.; Baldinger, T.; Wanner, J.; Jekle, A.; Heilek, G.; deRosier, A.; Ji, C.; Rotstein, D. M. Bioorg. Med. Chem. Lett. 2010, 20, 1674-1676
17. Rostein, D. M.; Gabriel, S. D.; Manser, N.; Filonova, L.; Padilla, F.; Sankuratri, S.; Ji., C.; deRosier, A.; Dioszegi, M.; Heilek, G.; Jekle, A.; Weller, P.; Berry, P. Bioorg. Med. Chem. Lett. 2010, 20, 3219-3222
18. Li, B.; Jones, E. D.; Zhou, E.; Li., C.; Baylis, D. C.; Yu, S.; Wang, M.; He, X.; Coates, J. A. V.; Rhodes, D. I.; Pei, G.; Deadman, J. J.; Xie, X.; Ma, D. Bioorg. Med. Chem. Lett. 2010, 20, 4012-4014
19. Palani, A.; Tagat, J. R. J. Med. Chem. 2006, 49, 2851-2857
20. Merck, 2010. http://www.merck.com/newsroom/news-release-archive/research- and-development/2010-0217.html; accessed on February 16, 2011.
21. Crabb, C. AIDS 2006, 20, 641
22. Moyle, G.; DeJesus, E.; Boffito, M.; Wong, R. S.; Gibney, C.; Badel, K.; MacFarland, R.; Calandra, G.; Bridger, G.; Becker, S. Clin. Infect. Dis. 2009, 48, 798-805
23. Tilton, J. C.; Wilen, C. B.; Didigu, C. A.; Sinha, R.; Harrison, J. E.; Agrawal-Gamse, C.; Henning, E. A.; Bushmannn, F. D.; Martin, J. N.; Deeks, S. G.; Doms, R. W. J. Virol. 2010, 84, 10863-10876
24. Labrecque, J.; Metz, M.; Lau, G.; Darkes, M. C.; Wong, R. S. Y.; Bogucki, D.; Carpenter, B.; Chen, G.; Li, T.; Nan, S.; Schols, D.; Bridger, G. J.; Fricker, S. P.; Skerlj., R. T. Virology 2011, 413, 231-243
25. Jamieson, C.; Moir, E. M.; Rankovic, Z.; Wishart, G. J. Med. Chem. 2006, 49, 5029-5046
26. Waring, M. J.; Johnstone, C. Bioorg. Med. Chem. Lett. 2007, 17, 1759-1764
27. Zhuo, Y.; Bourque, E.; Zhu, Y.; Langille, J.; Metz, M.; Yang, W.; McEachern, E. J.; Harwig, C.; Baird, I. R.; Li, T.; Skerlj, R. WO 2006/138350 A2.
28. Strizki, J. M. Antimicrob. Agents Chemother. 2005, 49, 4911-4919
29. Maeda, K.; Das, D.; Ogata-Aoki, H.; Nakata, H.; Miyakawa, T.; Tojo, Y.; Norman, R.; Takaoka, Y.; Ding, J.; Arnold, E.; Mitsuya, H. J. Biol. Chem. 2006, 281, 12688-12698
30. Billick, E.; Seibert, C.; Pugach, P.; Ketas, T.; Trkola, A.; Endres, M. J.; Murgolo, N. J.; Coates, E.; Reyes, G. R.; Baroudy, B. M.; Sakmar, T. P.; Moore, J. P.; Kuhmann, S. E. J. Virol. 2004, 78, 4134-4144
31. Dragic, T.; Trkola, A.; Thompson, D. A.; Cormier, E. G.; Kajumo, F. A.; Maxwell, E.; Lin, S. W.; Ying, W.; Smith, O. S.; Sakmar, T. P.; Moore, J. P. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 5639-5644
32. Castonguay, L. A.; Weng, Y.; Adolfsen, W.; Di Salvo, J.; Kilburn, R.; Caldwell, C. G.; Daugherty, B. L.; Finke, P. E.; Hale, J. J.; Lynch, C. L.; Mills, S. G.; MacCoss, M.; Springer, M. S.; DeMartino, J. A. Biochemistry 2003, 42, 1544-1550
33. Kondru, R.; Zhang, J.; Ji., C.; Mirzadegan, T.; Rotstein, D.; Sunkurati, S.; Dioszegi, M. Mol. Pharmacol. 2008, 73, 789-800
34. Nishikawa, M.; Takashima, K.; Nishi, T.; Furuta, R. A.; Kanzaki, N.; Yamamoto, Y.; Fujisawa, J.-I. Antimicrob. Agents Chemother. 2005, 49, 4708-4715
35. Stupple, P. A. J. Med. Chem. 2011, 54, 67-77
36. Seibert, C.; Ying, W.; Gavrilov, S.; Tsamis, F.; Kuhmann, S. E.; Palani, A.; Tagat, J. R.; Clader, J. W.; McCombie, S. W.; Baroudy, B. M.; Smith, S. O.; Dragic, T.; Moore, J. P.; Sakmar, T. P. Virology 2006, 349, 41-54
37. Tsamis, F.; Gavrilov, S.; Kajumo, F.; Seibert, C.; Kuhmann, S.; Ketas, T.; Trkola, A.; Palani, A.; Clader, J. W.; Tagat, J. R.; McCombie, S.; Baroudy, B.; Moore, J. P.; Sakmar, T. P.; Dragic, T. J. Virol. 2003, 77, 5201-5208
38. Gohlke, H.; Klebe, G. Angew. Chem. 2002, 114, 2764-2798
39. Angew. Chem., Int. Ed. 2002, 41, 2644-2676.
40. log D is a measure of lipophilicity: ACD/PhysChemBatch; ACD/Labs Release: 12.00 Product Version: 12.01; www.acdlabs.com.
41. Zhou, Y.; Bourque, E.; Zhu, Y.; McEachern, E. J.; Harwig, C.; Skerlj, R. T.; Bridger, G. J.; Li, T.; Metz, M. WO 2007/022371 A2.
42. Bourque, E.; Metz, M.; Baird, I. R.; Yang, W.; Bridger, G.; Skerlj, R. T. WO 2008/070758 A1.
43. Ballesteros, J. A.; Weinstein, H. Methods Neurosci. 1995, 25, 366-428
44. Berkhout, T. A.; Blaney, F. E.; Bridges, A. M.; Cooper, D. G.; Forbes, I. T.; Gribble, A. D.; Groot, P. H. E.; Hardy, A.; Ife, R. J.; Kaur, R.; Moores, K. E.; Shillito, H.; Willetts, J.; Witherington, J. J. Med. Chem. 2003, 46, 4070-4086
45. Wong, R. S. Y.; Bodard, V.; Metz, M.; Labrecque, J.; Bridger, G.; Fricker, S. P. Mol. Pharmacol. 2008, 74, 1485-1495
46. Rosenkkilde, M. M.; Gerlach, L.-O.; Jakobson, J. S.; Skerlj, R. T.; Bridger, G. J.; Schwartz, T. W. J. Biol. Chem. 2004, 279, 3033-3041
47. Arias, A. D.; Navenot, J.-M.; Zhang, Z.-B.; Broach, J.; Peiper, S. C. J. Biol. Chem. 2003, 278, 36513-36521
48. Govaerts, C.; Bondue, A.; Springael, J.-Y.; Olivella, M.; Deupi, X.; Le Poul, E.; Wodak, S. J.; Parmentier, M; Pardo, L.; Blanpain, C. J. Biol. Chem. 2003, 278, 1892-1903
49. Wei, B.; Chien, E. Y. T.; Mol, C. D.; Fenalti, G.; Liu, W.; Katritch, V.; Abagyan, R.; Brooun, A.; Wells, P.; Bi, F. C.; Hamel, D. J.; Kuhn, P.; Handel, T. M. Science 2010, 330, 1066-1071
50. Kenakin, T. Recept. Channels 2004, 10, 51-60
51. Kenakin, T. Nat. Rev. Drug Discovery 2005, 4, 919-927
52. Ballesteros, J. A.; Shi, L.; Javitch, J. A. Mol. Pharmacol. 2001, 60, 1-19