Synthesis, in vitro evaluation and cocrystal structure of 4-oxo-[1]benzopyrano[4,3-c]pyrazole cryptosporidium parvum inosine 5′-monophosphate dehydrogenase (Cp IMPDH) inhibitors

Journal of Medicinal Chemistry

Volumn 57, Issue 24, 2014, Pages 10544-10550

  Sun, Zhuming ^a   Khan, Jihan ^b   Makowska Grzyska, Magdalena ^c   Zhang, Minjia ^b   Cho, Joon Hyung ^a   Suebsuwong, Chalada ^a   Vo, Pascal ^a   Gollapalli, Deviprasad R ^b   Kim, Youngchang ^c,d   Joachimiak, Andrzej ^c,d   Hedstrom, Lizbeth ^b   Cuny, Gregory D ^a  

^a UNIVERSITY OF HOUSTON   (United States)

^b BRANDEIS UNIVERSITY   (United States)

^c UNIVERSITY OF CHICAGO   (United States)

^d ARGONNE NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 OXO [1]BENZOPYRANO[4,3 C]PYRAZOLE DERIVATIVE; CRYPTOSPORIDIUM INOSINE 5' MONOPHOSPHATE DEHYDROGENASE INHIBITOR; GUANINE NUCLEOTIDE; OXIDOREDUCTASE INHIBITOR; PYRAZOLE DERIVATIVE; UNCLASSIFIED DRUG; 4-OXO-N-(3-METHOXYPHENYL)-(1)BENZOPYRANO(4,3-C)PYRAZOLE-1(4H)-ACETAMIDE; ACETANILIDE DERIVATIVE; COUMARIN DERIVATIVE; ENZYME INHIBITOR; INOSINATE DEHYDROGENASE; PYRAZOLE;

ARTICLE; CONFORMATION; CRYPTOSPORIDIUM PARVUM; CRYSTAL STRUCTURE; DRUG IDENTIFICATION; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; IN VITRO STUDY; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECTS; ENZYMOLOGY; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ACETANILIDES; COUMARINS; CRYPTOSPORIDIUM PARVUM; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; IMP DEHYDROGENASE; IN VITRO TECHNIQUES; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PYRAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84920129978     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm501527z     Document Type: Article

References (27)

1. Striepen, B. Parasitic infections: time to tackle cryptosporidiosis Nature 2013, 503, 189-191
2. Guerrant, R. L.; Oria, R. B.; Moore, S. R.; Oria, M. O.; Lima, A. A. Malnutrition as an enteric infectious disease with long-term effects on child development Nutr. Rev. 2008, 66, 487-505
3. Fayer, R. Cryptosporidium: a water-borne zoonotic parasite Vet. Parasitol. 2004, 126, 37-56
4. DuPont, H. L.; Chappell, C. L.; Sterling, C. R.; Okhuysen, P. C.; Rose, J. B.; Jakubowski, W. The infectivity of Cryptosporidium parvum in healthy volunteers N. Engl. J. Med. 1995, 332, 855-859
5. Mead, J. R. Cryptosporidiosis and the challenges of chemotherapy Drug Resist. Updates 2002, 5, 47-57
6. Hedstrom, L. IMP dehydrogenase: structure, mechanism, and inhibition Chem. Rev. 2009, 109, 2903-2928
7. Striepen, B.; Pruijssers, A. J.; Huang, J.; Li, C.; Gubbels, M. J.; Umejiego, N. N.; Hedstrom, L.; Kissinger, J. C. Gene transfer in the evolution of parasite nucleotide biosynthesis Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 3154-3159
8. Xu, P.; Widmer, G.; Wang, Y.; Ozaki, L. S.; Alves, J. M.; Serrano, M. G.; Puiu, D.; Manque, P.; Akiyoshi, D.; Mackey, A. J.; Pearson, W. R.; Dear, P. H.; Bankier, A. T.; Peterson, D. L.; Abrahamsen, M. S.; Kapur, V.; Tzipori, S.; Buck, G. A. The genome of Cryptosporidium hominis Nature 2004, 431, 1107-1112
9. Abrahamsen, M. S.; Templeton, T. J.; Enomoto, S.; Abrahante, J. E.; Zhu, G.; Lancto, C. A.; Deng, M.; Liu, C.; Widmer, G.; Tzipori, S.; Buck, G. A.; Xu, P.; Bankier, A. T.; Dear, P. H.; Konfortov, B. A.; Spriggs, H. F.; Iyer, L.; Anantharaman, V.; Aravind, L.; Kapur, V. Complete genome sequence of the apicomplexan Cryptosporidium parvum Science 2004, 304, 441-445
10. Striepen, B.; White, M. W.; Li, C.; Guerini, M. N.; Malik, S. B.; Logsdon, J. M., Jr.; Liu, C.; Abrahamsen, M. S. Genetic complementation in apicomplexan parasites Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 6304-6309
11. Allison, A. C.; Kowalski, W. J.; Muller, C. D.; Eugui, E. M. Mechanisms of action of mycophenolic acid Ann. N. Y. Acad. Sci. 1993, 696, 63-87
12. Allison, A. C.; Eugui, E. M. Mycophenolate mofetil and its mechanisms of action Immunopharmacology 2000, 47, 85-118
13. Umejiego, N. N.; Gollapalli, D.; Sharling, L.; Volftsun, A.; Lu, J.; Benjamin, N. N.; Stroupe, A. H.; Riera, T. V.; Striepen, B.; Hedstrom, L. Targeting a prokaryotic protein in a eukaryotic pathogen: identification of lead compounds against cryptosporidiosis Chem. Biol. 2008, 15, 70-77
14. Hedstrom, L.; Liechti, G.; Goldberg, J. B.; Gollapalli, D. R. The antibiotic potential of prokaryotic IMP dehydrogenase inhibitors Curr. Med. Chem. 2011, 18, 1909-1918
15. Mandapati, K.; Gorla, S. K.; House, A. L.; McKenney, E. S.; Zhang, M.; Rao, S. N.; Gollapalli, D. R.; Mann, B. J.; Goldberg, J. B.; Cuny, G. D.; Glomski, I. J.; Hedstrom, L. Repurposing Cryptosporidium inosine 5′-monophosphate dehydrogenase inhibitors as potential antibacterial agents ACS. Med. Chem. Lett. 2014, 5, 846-850
16. Gorla, S. K.; Kavitha, M.; Zhang, M.; Chin, J. E.; Liu, X.; Striepen, B.; Makowska-Grzyska, M.; Kim, Y.; Joachimiak, A.; Hedstrom, L.; Cuny, G. D. Optimization of benzoxazole-based inhibitors of Cryptosporidium parvum inosine 5′-mono phosphate dehydrogenase J. Med. Chem. 2013, 56, 4028-4043
17. Gorla, S. K.; Kavitha, M.; Zhang, M.; Liu, X.; Sharling, L.; Gollapalli, D. R.; Striepen, B.; Hedstrom, L.; Cuny, G. D. Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5′-monophosphate dehydrogenase J. Med. Chem. 2012, 55, 7759-7771
18. Johnson, C. R.; Gorla, S. K.; Kavitha, M.; Zhang, M.; Liu, X.; Striepen, B.; Mead, J. R.; Cuny, G. D.; Hedstrom, L. Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum Bioorg. Med. Chem. Lett. 2013, 23, 1004-1007
19. Kirubakaran, S.; Gorla, S. K.; Sharling, L.; Zhang, M.; Liu, X.; Ray, S. S.; Macpherson, I. S.; Striepen, B.; Hedstrom, L.; Cuny, G. D. Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH Bioorg. Med. Chem. Lett. 2012, 22, 1985-1988
20. Gorla, S. K.; McNair, N. N.; Yang, G.; Gao, S.; Hu, M.; Jala, V. R.; Haribabu, B.; Striepen, B.; Cuny, G. D.; Mead, J. R.; Hedstrom, L. Validation of IMP dehydrogenase inhibitors in a mouse model of cryptosporidiosis Antimicrob. Agents Chemother. 2014, 58, 1603-1614
21. Leleti, M. R.; Pennell, A. M. K.; Thomas, W. D.; Zhang, P. CXCR4 modulators. WO2007115231, 2007.
22. Sosnovskikh, V. Y.; Moshkin, V. S.; Kodess, M. I. On the reaction of 3-cyanochromones with phenyl- and methylhydrazines: Structural revision and a simple synthesis of chromeno[4,3- c ]pyrazol-4-ones J. Heterocycl. Chem. 2010, 47, 629-633
23. Farazi, T.; Leichman, J.; Harris, T.; Cahoon, M.; Hedstrom, L. Isolation and characterization of mycophenolic acid-resistant mutants of inosine-5′-monophosphate dehydrogenase J. Biol. Chem. 1997, 272, 961-965
24. Mortimer, S. E.; Hedstrom, L. Autosomal dominant retinitis pigmentosa mutations in inosine 5′-monophosphate dehydrogenase type I disrupt nucleic acid binding Biochem. J. 2005, 390, 41-47
25. Umejiego, N. N.; Li, C.; Riera, T.; Hedstrom, L.; Striepen, B. Cryptosporidium parvum IMP dehydrogenase: identification of functional, structural, and dynamic properties that can be exploited for drug design J. Biol. Chem. 2004, 279, 40320-40327
26. MacPherson, I. S.; Kirubakaran, S.; Gorla, S. K.; Riera, T. V.; D'Aquino, J. A.; Zhang, M.; Cuny, G. D.; Hedstrom, L. The structural basis of Cryptosporidium -specific IMP dehydrogenase inhibitor selectivity J. Am. Chem. Soc. 2010, 132, 1230-1231
27. Allen, F. H.; Baalham, C. A.; Lommerse, J. P. M.; Raithby, P. R. Carbonyl-carbonyl interactions can be competitive with hydrogen bonds Acta Crystallogr., Sect. B: Struct. Sci. 1998, B54, 320-329