Protein farnesyltransferase inhibitors exhibit potent antimalarial activity

Journal of Medicinal Chemistry

Volumn 48, Issue 11, 2005, Pages 3704-3713

  Nallan, Laxman ^a   Bauer, Kevin D ^a   Bendale, Pravin ^a   Rivas, Kasey ^a   Yokoyama, Kohei ^a   Hornéy, Carolyn P ^a   Pendyala, Prakash Rao ^c   Floyd, David ^d   Lombardo, Louis J ^d   Williams, David K ^d   Hamilton, Andrew ^e   Sebti, Said ^h   Windsor, William T ^f   Weber, Patricia C ^f,g   Buckner, Frederick S ^a   Chakrabarti, Debopam ^c   Gelb, Michael H ^a,b   Van Voorhis, Wesley C ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF CENTRAL FLORIDA   (United States)

^d BRISTOL MYERS SQUIBB PHARMACEUTICAL RESEARCH INSTITUTE   (United States)

^e YALE UNIVERSITY   (United States)

^f MERCK RESEARCH LABORATORIES   (United States)

^g Imiplex   (United States)

^h NONE

Author keywords

[No Author keywords available]

Indexed keywords

1 METHYL 1H IMIDAZOLE 4 SULFONIC ACID (1 BROMONAPHTHALEN 2 YLMETHYL)[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL]AMIDE; 1 METHYL 1H IMIDAZOLE 4 SULFONIC ACID (2 BROMOALLYL)[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 2 YL]AMIDE; 1 METHYL 1H IMIDAZOLE 4 SULFONIC ACID [6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](2 METHYLALLYL)AMIDE; 1 METHYL 1H IMIDAZOLE 4 SULFONIC ACID [6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](2 METHYLBENZYL)AMIDE; 1 METHYL 1H IMIDAZOLE 4 SULFONIC ACID BENZYL [6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL]AMIDE; 3 BENZYL 7 CYANO 2,3,4,5 TETRAHYDRO 1 (1H IMIDAZOL 4 YLMETHYL) 4 (2 THIENYLSULFONYL) 1H 1,4 BENZODIAZEPINE; 4 [[[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](1 METHYL 1H IMIDAZOLE 4 SULFONYL)AMINO]METHYL]PIPERIDINE 1 CARBOXYLIC ACID TERT BUTYL ESTER; [[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](1 METHYL 1H IMIDAZOLE 4 SULFONYL)AMINO]ACETIC ACID TERT BUTYL ESTER; A 197574; A 345677; BMS 339941; BMS 386914; BMS 388891; CHLOROQUINE; FTI 2148; LONAFARNIB; MSD 1; N TERT BUTYL 1 [[6 ISOCYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](PYRIDINE 3 SULFONYL)AMINO]ACETAMIDE; N TERT BUTYL 2 [[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](1 METHYL 1H IMIDAZOLE 2 SULFONYL)AMINO]ACETAMIDE; N TERT BUTYL 2 [[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](1 METHYL 1H IMIDAZOLE 4 SULFONYL)AMINO]ACETAMIDE; N TERT BUTYL 2 [[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](4 FLUOROBENZENESULFONYL)AMINO]ACETAMIDE; N TERT BUTYL 2 [[6 ISOCYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](PYRIDINE 2 SULFONYL)AMINO]ACETAMIDE; N TERT BUTYL 2 [[6 ISOCYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](PYRIDINE 4 SULFONYL)AMINO]ACETAMIDE; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PYRIDINE 2 SULFONIC ACID (1 BROMONAPHTHALEN 2 YLMETHYL)[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL]AMIDE; PYRIDINE 2 SULFONIC ACID (6 CHLOROBENZO[1,2,5]THIADIAZOL 5 YLMETHYL)[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL]AMIDE; PYRIDINE 2 SULFONIC ACID [6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](5 METHYL 3 PHENYLISOXAZOL 4 YLMETHYL)AMIDE; PYRIDINE 2 SULFONIC ACID [6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL]PYRIDIN 2 YLMETHYLAMIDE; QUINOLINE DERIVATIVE; TETRAHYDROQUINOLINE; TIPIFARNIB; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG MECHANISM; DRUG POTENCY; DRUG TARGETING; DRUG TOLERABILITY; ENZYME INHIBITION; FEMALE; MALARIA; MOUSE; NONHUMAN; OSMOTIC PUMP; PARASITEMIA; PLASMODIUM FALCIPARUM; STRUCTURE ACTIVITY RELATION;

ALKYL AND ARYL TRANSFERASES; ANIMALS; ANTIMALARIALS; CELLS, CULTURED; ELECTROPHORESIS, POLYACRYLAMIDE GEL; ERYTHROCYTES; FARNESYLTRANSTRANSFERASE; FEMALE; HUMANS; MALARIA; MICE; MICE, INBRED BALB C; MICROSCOPY, FLUORESCENCE; PLASMODIUM BERGHEI; PLASMODIUM FALCIPARUM; PROTEIN ISOPRENYLATION; QUINOLONES; RATS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 20144373679     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0491039     Document Type: Article

References (27)

1. www.mmv.org. 2003.
2. Gelb, M. H.; Hol, W. G. Parasitology. Drugs to combat tropical protozoan parasites. Science 2002, 297, 343-344.
3. Leonard, D. M. Ras farnesyltransferase: a new therapeutic target. J. Med. Chem. 1997, 40, 2971-2990.
4. Cox, A. D.; Der, C. J. Ras family signaling: therapeutic targeting. Cancer Biol. Ther. 2002, 1, 599-606.
5. Sebti, S. M.; Hamilton, A. D.; Moffitt, H. L. Farnesyltransferase Inhibitors in Cancer Therapy; Humana Press: Totowa, NJ, 2001.
6. Yokoyama, K.; Goodwin, G. W.; Ghomashchi, F.; Glomset, J.; and Gelb, M. H. Protein prenyltransferases. Biochem. Soc. Trans. 1992, 20, 489-494.
7. Chakrabarti, D.; Da Silva, T.; Barger, J.; Paquette, S.; Patel, H.; Patterson, S.; Allen, C. M. Protein farnesyltransferase and protein prenylation in Plasmodium falciparum. J. Biol. Chem. 2002, 277, 42066-42073.
8. Chakrabarti, D.; Azam, T.; DelVecchio, C.; Qiu, L.; Park, Y. I.; Allen, C. M. Protein prenyl transferase activities of Plasmodium falciparum. Mol. Biochem. Parasitol. 1998, 94, 175-184.
9. www.plasmodb.org. 2003.
10. Lombardo, L. J.; Camuso, A.; Clark, J.; Fager, K.; Gullo-Brown, J.; Hunt, J. T.; Inigo, I.; Kan, D.; Kolowitz, B.; Lee, F.; McGlinchey, K.; Qian, L.; Ricca, C.; Rovnyak, G.; Traeger, S.; Tokarski, J.; Williams, D. K.; Wu, L. I.; Zhao, Y.; Manne, V.; Bhide, R. S. Design, synthesis and structure-activity relationships of tetrahydroquinoline-based farnesyltransferase inhibitors. Bioorg. Med. Chem. Lett. 2005, 15, 1895-1899.
11. Chen, B.-C.; Sundeen, J. E.; Guo, P.; Bednarz, M. S.; Zhao, R. Novel triethylsilane mediated reductive N-alkylation of amines: improved synthesis of 1-(4-imidazolyl)methyl-4-sulfonylbenzodiazepines, new farnesyltransferase inhibitors. Tetrahedron Lett. 2001, 42, 1245-1246.
12. Gwaltney, S. L.; O'Connor, S. J.; Nelson, L. T.; Sullivan, G. M.; Imade, H.; Wang, W.; Hasvold, L.; Li, Q.; Cohen, J.; Gu, W. Z.; Tahir, S. K.; Bauch, J.; Marsh, K.; Ng, S. C.; Frost, D. J.; Zhang, H.; Muchmore, S.; Jakob, C. G.; Stoll, V.; Hutchins, C.; Rosenberg, S. H.; Sham, H. L. Aryl tetrahydropyridine inhibitors of farnesyltransferase: bioavailable analogues with improved cellular potency. Bioorg. Med. Chem. Lett. 2003, 13, 1363-1366.
13. Hunt, J. T.; Ding, C. Z.; Batorsky, R.; Bednarz, M.; Bhide, R.; Cho, Y.; Chong, S.; Chao, S.; Gullo-Brown, J.; Guo, P.; Kim, S. H.; Lee, F. Y.; Leftheris, K.; Miller, A.; Mitt, T.; Patel, M.; Penhallow, B. A.; Ricca, C.; Rose, W. C.; Schmidt, R.; Slusarchyk, W. A.; Vite, G.; Manne, V. Discovery of (R)-7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl) -4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine (BMS-214662), a farnesyltransferase inhibitor with potent preclinical antitumor activity. J. Med. Chem. 2000, 43, 3587-3595.
14. End, D. W.; Smets, G.; Todd, A. V.; Applegate, T. L.; Fuery, C. J.; Angibaud, P.; Venet, M.; Sanz, G.; Poignet, H.; Skrzat, S.; Devine, A.; Wouters, W.; Bowden, C. Characterization of the antitumor effects of the selective farnesyl protein transferase inhibitor R115777 in vivo and in vitro. Cancer Res. 2001, 61, 131-137.
15. Bell, I. M.; Gallicchio, S. N.; Abrams, M.; Beshore, D. C.; Buser, C. A.; Culberson, J. C.; Davide, J.; Ellis-Hutchings, M.; Fernandes, C.; Gibbs, J. B.; Graham, S. L.; Hartman, G. D.; Heimbrook, D. C.; Homnick, C. F.; Huff, J. R.; Kassahun, K.; Koblan, K. S.; Kohl, N. E.; Lobeil, R. B.; Lynch, J. J., Jr.; Miller, P. A.; Omer, C. A.; Rodrigues, A. D.; Walsh, E. S.; Williams, T. M. Design and biological activity of (S)-4-(5-([1-(3-chlorobenzyl)-2-oxopyrrolidin- 3-ylamino]methyl)imidazol-1-ylmethyl)benzonitrile, a 3-aminopyrrolidinone farnesyltransferase inhibitor with excellent cell potency. J. Med. Chem. 2001, 44, 2933-2949.
16. Taveras, A. G.; Kirschmeier, P.; Baum, C. M. Sch-66336 (sarasar) and other benzocycloheptapyridyl farnesyl protein transferase inhibitors: discovery, biology and clinical observations. Curr. Top. Med. Chem. 2003, 3, 1103-1114.
17. Ohkanda, J.; Knowles, D. B.; Blaskovich, M. A.; Sebti, S. M.; Hamilton, A. D. Inhibitors of protein farnesyltransferase as novel anticancer agents. Curr. Top. Med. Chem. 2002, 2, 303-323.
18. Carrico, D.; Ohkanda, J.; Kendrick, H.; Yokoyama, K.; Blaskovich, M. A.; Bucher, C. J.; Buckner, F. S.; Van Voorhis, W. C.; Chakrabarti, D.; Croft, S. L.; Gelb, M. H.; Sebti, S. M.; Hamilton, A. D. In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability. Bioorg. Med. Chem. 2004, 12, 6517-6526.
19. Eastman, R. T.; White, J.; Hucke, O.; Bauer, K.; Yokoyama, K.; Nallan, L.; Chakrabarti, D.; Verlinde, C. M. J.; Gelb, M. H.; Rathad, P. K.; Van Voorhis, W. C. Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum. J Biol. Chem. 2005, 250, 13554-13559.
20. Vennerstrom, J. L.; Arbe-Barnes, S.; Brun, R.; Charman, S. A.; Chiu, F. C.; Chollet, J.; Dong, Y.; Dorn, A.; Hunziker, D.; Matile, H.; McIntosh, K.; Padmanilayam, M.; Santo, T. J.; Scheurer, C.; Scorneaux, B.; Tang, Y.; Urwyler, H.; Wittlin, S.; Charman, W. N. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature 2004, 430, 900-904.
21. Wiesner, J.; Kettler, K.; Sakowski, J.; Ortmann, R.; Katzin, A. M.; Kimura, E. A.; Silber, K.; Klebe, G.; Jomaa, H.; Schlitzer, M. Farnesyltransferase inhibitors inhibit the growth of malaria parasites in vitro and in vivo. Angew. Chem., Int. Ed 2004, 43, 251-254.
22. Angibaud, P. R.; Vanet, M. G.: Filliers, W.; Broecks, R.; Ligny, Y. A.; Muller, P.; Poncelet, V. S.; End, D. W. Synthesis Routes Towards the Farnesyl Protein Transferase Inhibitor Zarnestra. Eur. J. Org. Chem. 2004, 479-486.
23. Ohkanda, J.; Buckner, F. S.; Lockman, J. W.; Yokoyama, K.; Carrico, D.; Eastman, R.; Luca-Fradley, K.; Davies, W.; Croft, S. L.; Van Voorhis, W. C.; Gelb, M. H.; Sebti, S. M.; Hamilton, A. D. Design and synthesis of peptidomimetic protein farnesyl-transferase inhibitors as anti-Trypanosoma brucei agents. J. Med. Chem. 2004, 47, 432-445.
24. Corey, E. J.; Posner, G. H.; Atkinson, R. F.; Wingard, A. K.; Halloran, D. J.; Radzik, D. M.; Nash, J. J. Formation of Olefins Via Pyrolysis of Sulfonate Esters. J. Org. Chem. 1989, 54, 389-393.
25. Trager, W. and Jensen, J. B. Human malaria parasites in continuous culture. Science 1976, 193, 673-675.
26. Yokoyama, K.; Zimmerman, K.; Scholten, J.; Gelb, M. H. Differential prenyl pyrophosphate binding to mammalian protein geranylgeranyltransferase-I and protein farnesyltransferase and its consequence on the specificity of protein prenylation. J Biol. Chem. 1997, 272, 3944-3952.
27. Lambros, C. and Vanderberg, J. P. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J. Parasitol. 1979, 65, 418-420.