Second generation tetrahydroquinoline-based protein farnesyltransferase inhibitors as antimalarials

Journal of Medicinal Chemistry

Volumn 50, Issue 19, 2007, Pages 4585-4605

  Bendale, Pravin ^a   Olepu, Srinivas ^a   Suryadevara, Praveen Kumar ^a   Bulbule, Vivek ^a   Rivas, Kasey ^a   Nallan, Laxman ^a   Smart, Brian ^a   Yokoyama, Kohei ^a   Ankala, Sudha ^a   Pendyala, Prakash Rao ^b   Floyd, David ^c   Lombardo, Louis J ^d   Williams, David K ^d   Buckner, Frederick S ^a   Chakrabarti, Debopam ^b   Verlinde, Christophe L M J ^a   Van Voorhis, Wesley C ^a   Gelb, Michael H ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF CENTRAL FLORIDA   (United States)

^c PHARMACOPEIA INC   (United States)

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

Author keywords

[No Author keywords available]

Indexed keywords

4 [[[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](1,5 DIMETHYL 1H IMIDAZOLE 4 SULFONYL)AMINO]METHYL]PIPERIDINE 1 CARBOXYLIC ACID METHYL ESTER; 4 [[[6 CYANO 1 (3 METHYL 3H IMIDAZOL 4 YLMETHYL) 1,2,3,4 TETRAHYDROQUINOLIN 3 YL](PYRIDINE 2 SULFONYL)AMINO]METHYL]PIPERIDINE 1 CARBOXYLIC ACID METHYL ESTER; ANTIMALARIAL AGENT; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVITY; ENZYME INHIBITION; IC 50; PLASMODIUM FALCIPARUM; PROTON NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; SEQUENCE HOMOLOGY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; X RAY ANALYSIS;

ANIMALS; ANTIMALARIALS; BINDING SITES; COMBINATORIAL CHEMISTRY TECHNIQUES; CRYSTALLOGRAPHY, X-RAY; FARNESYLTRANSTRANSFERASE; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PLASMODIUM FALCIPARUM; QUINOLINES; RATS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 34648816239     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0703340     Document Type: Article

References (24)

1. Chakrabarti, D.; Azam, T.; DelVecchio, C.; Qiu, L.; Park, Y.: Allen, C. M. Protein prenyl transferase activities of Plasmodium falciparum. Mol. Biochem. Parasitol. 1998, 94, 175-184.
2. 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.
3. Nallan, L.; Bauer, K. D.; Bendale, P.; Rivas, K.; Yokoyama, K.; Horney, C. P.; Pendyala, P. R.; Floyd, D.; Lombardo, L. J.; Williams, D. K.; Hamilton, A.; Sebti, S.; Windsor, W. T.; Weber, P. C.; Buckner, F. S.; Chakrabarti, D.; Gelb, M. H.; Van Voorhis, W. C. Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. J. Med. Chem. 2005, 48, 3704-3713.
4. Bell, I. M. Inhibitors of farnesyltransferase: A rational approach to cancer chemotherapy? J. Med. Chem. 2004, 47, 1869-1878.
5. Lombardo, L. J.; Camuso, A.; Clark J.; Fager K.; Gullo-Brown J.; Hunt J. T.; Inigo I.; Kan D.; Koplowitz 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 tetrahyroquinoline-based farnesyltransferase inhibitors. Bioorg. Med. Chem. Lett. 2005, 15, 1895-1899.
6. 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.
7. Eastman, R. T.; White, J.; Hucke, O.; Bauer, K.; Yokoyama, K.; Nallan, L.; Chakrabarti, D.; Verlinde, C. L.; Gelb, M. H.; Rathod, P. K.; Van Voorhis, W. C. Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum. J. Biol. Chem. 2005, 280, 13554-13559.
8. Eastman, R. T.; White, J.; Hucke, O.; Yokoyama, K.; Verlinde, C. L.; Hast, M. A.; Beese, L. S.; Gelb, M. H.; Rathod, P. K.; Van Voorhis, W. C. Resistance mutations at the lipid substrate binding site of Plasmodium falciparum protein farnesyltransferase. Mol. Biochem. Parasitol. 2007, 152 (1), 66-71.
9. Van Voorhis, W. C.; Rivas, K.; Bendale, P.; Nallan, L.; Hornéy, C.; Barrett, L. K.; Ankala, S.; Hucke, O.; Verlinde, C. L. M. J.; Chakrabarti, D.; Strickland, C.; Yokoyama, K.; Buckner, F. S.; Hamilton, A.; Williams, D. K.; Lombardo, L. J.; Floyd, D.; Gelb, M. H. Tetrahydroquinoline Plasmodium falciparum protein farnesyltransferase inhibitors: Efficacy, pharmacokinetics, and metabolism. Antimicrob. Agents Chemother. 2007, in press.
10. Bhide, R. Inhibitors of farnesyl protein transferase. WO 99/01434, 1999.
11. Reid, T. S.; Beese, L. S. Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity. Biochemistry 2004, 43, 6877-6884.
12. Nicholas, J. B.; Vance, R. E. M.; Burke, B. J.; Hopfinger, A. J. A molecular mechanics valence force field for sulfonamides derived by ab initio methods. J. Chem. Phys. 1991, 95, 9803-9811.
13. Liang, G. Y.; Bays, J. P.; Bowen, J. P. Ab initio calculations and molecular mechanics (MM3) force field development for sulfonamide and its alkyl derivatives. Theochem. 1997, 40, 1/2, 165-179.
14. Hillal, S. H.; Karickhoff, S. W.; Carreira, L. A. A rigorous test for SPARC'S chemical reactivity models: Estimation of more than 4300 ionization pK(a)s. Quant. Struct.-Act. Relat. 1995, 14, 348.
15. a of pharmaceutical substances using the computer program spare. Talanta 1996, 43, 607-619.
16. Chen, B. C.; Skoumbourdis, A. P.; Sundenen, J. E.; Rovnyak, G. C.; Traeger, S. C. Efficient molar-scale synthesis of 1-methyl-5-acylimidazole triflic acid salts. Org. Process Res. Dev. 2000, 4, 513-614.
17. Kelley, J. L.; Miller, C. A.; McLean, E. W. Attempted inhibition of histidine decarboxylase with β-alkyl analogues of histidine. J. Med. Chem. 1977, 20, 721-723.
18. Venishi, J.; Hamada, M.; Aburatani, S.; Matsui, K.; Yonemitsu, O.; Tsukube, H. Synthesis of chiral nonracemic 1-(2-pyridinyl)ethylamines: Stereospecific introduction of amino function onto the 2-pyridinylmethyl carbon center. J. Org. Chem. 2004, 69, 6781-6789.
19. Sali, A.; Blundell, T. L. Comparative protein modelling by satisfaction of spatial restraints. J. Mol. Biol. 1993, 234, 779-815.
20. Bahl, A.; Brunk, B.; Crabtree, J.; Fraunholz, M. J.; Gajria, B.; Grant, G. R.; Ginsburg, H.; Gupta, D.; Kissinger, J. C.; Labo, P.; Li, L.; Mailman, M. D.; Milgram, A. J.; Pearson, D. S.; Roos, D. S.; Schug, J.; Stoeckert, C. J., Jr.; Whetzel, P. PlasmoDB: The Plasmodium genome resource. A database integrating experimental and computational data. Nucleic Acids Res. 2003, 31, 212-215.
21. Gu, J. M.; Hu, X. R.; Xu, W. M. 7-Nitro-1,2,3,4-tetrahydroquinoline. Acta Crystallogr. 2006, E62, o62-o63.
22. Trager, W.; Jensen, J. B. Human malaria parasites in continuous culture. Science 1976, 193, 673-675.
23. 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.
24. McMartin, C.; Bohacek, R. S. QXP: Powerful, rapid computer algorithms for structure-based drug design. J. Comput.-Aided Mol. Des. 1997, 11, 333-344.