Synthesis and biological evaluation of (hetero)arylmethyloxy- and arylmethylamine-phenyl derivatives as potent P-glycoprotein modulating agents

Journal of Medicinal Chemistry

Volumn 51, Issue 5, 2008, Pages 1415-1422

  Colabufo, Nicola Antonio ^a   Berardi, Francesco ^a   Perrone, Roberto ^a   Rapposelli, Simona ^b   Digiacomo, Maria ^b   Vanni, Michael ^b   Balsamo, Aldo ^b  

^a UNIVERSITY OF BARI   (Italy)

^b UNIVERSITY OF PISA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

1 [(2 METHOXYBENZYL)OXY] 2 (2 PHENYLETHYL)BENZENE; 1 [(2 METHOXYBENZYL)OXY] 2 [2 (3 METHOXYPHENYL)ETHYL]BENZENE; 1 [(2,3 DIMETHOXYBENZYL)OXY] 2 (2 PHENYLETHYL)BENZENE; 1 [(2,3 DIMETHOXYBENZYL)OXY] 2 [2 (3 METHOXYPHENYL)ETHYL]BENZENE; 1 [(3,4 DIMETHOXYBENZYL)OXY] 2 (2 PHENYLETHYL)BENZENE; 1 [(3,4 DIMETHOXYBENZYL)OXY] 2 [2 (3 METHOXYPHENYL)ETHYL]BENZENE; 1 [(3,5 DIMETHOXYBENZYL)OXY] 2 (2 PHENYLETHYL)BENZENE; 1 [(3,5 DIMETHOXYBENZYL)OXY] 2 [2 (3 METHOXYPHENYL)ETHYL]BENZENE; 1 [(4 METHOXYBENZYL)OXY] 2 (2 PHENYLETHYL)BENZENE; 1 [(4 METHOXYBENZYL)OXY] 2 [2 (3 METHOXYPHENYL)ETHYL]BENZENE; BREAST CANCER RESISTANCE PROTEIN; CYCLOSPORIN A; ELACRIDAR; GLYCOPROTEIN P INHIBITOR; N (2 METHOXYBENZYL) 2 [2 (3 METHOXYPHENYL)ETHYL]ANILINE; N (3 METHOXYBENZYL) 2 [2 (3 METHOXYPHENYL)ETHYL]ANILINE; N (4 METHOXYBENZYL) 2 [2 (3 METHOXYPHENYL)ETHYL]ANILINE; N [(2,3 DIMETHOXY)BENZYL] 2 [2 (3 METHOXYPHENYL)ETHYL]ANILINE; N [(3,4 DIMETHOXY)BENZYL] 2 [2 (3 METHOXYPHENYL)ETHYL]ANILINE; N [(3,5 DIMETHOXY)BENZYL] 2 [2 (3 METHOXYPHENYL)ETHYL]ANILINE; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG; VERAPAMIL;

ARTICLE; BIOLOGICAL ACTIVITY; CONTROLLED STUDY; DRUG MECHANISM; DRUG SYNTHESIS; HUMAN; HUMAN CELL; PROTEIN FUNCTION;

ATP-BINDING CASSETTE TRANSPORTERS; BENZENE DERIVATIVES; BIOLOGICAL TRANSPORT; CELL LINE, TUMOR; CELL MEMBRANE PERMEABILITY; DRUG RESISTANCE, NEOPLASM; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; METHYLAMINES; NEOPLASM PROTEINS; P-GLYCOPROTEIN; PYRIDINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 41649088805     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm701267q     Document Type: Article

References (34)

1. Klein, I.; Sarkadi, B.; Varadi, A. An inventory of the human ABC proteins. Biochim. Biophys. Acta 1999, 1461, 237-262.
2. Ambudkar, S. V.; Dey, S.; Hrycyna, C. A.; Ramachandra, M.; Pastan, I.; Gottesman, M. M. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 1999, 39, 361-398.
3. Ayrton, A.; Morgan, P. Role of transport proteins in drug absorption, distribution, and excretion. Xenobiotica 2001, 31, 469-491.
4. Dean, M.; Rzhetsky, A.; Allikmets, R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001, 11, 1156-1166.
5. Hyde, S. C.; Emsley, P.; Hartshorn, M. J.; Mimmack, M. M.; Gileadi, U.; Pearce, S. R.; Gallagher, M. P.; Gill, D. R.; Hubbard, R. E.; Higgins, C. F. Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance, and bacterial transport. Nature 1990, 346, 362-365.
6. Quinton, P. M. Physiological basis of cystic fibrosis: a historical perspective. Physiol. Rev. 1999, 79, S3-S22.
7. Remaley, A. T.; Rust, S.; Rosier, M.; Knapper, C.; Naudin, L.; Broccardo, C.; Peterson, K. M.; Koch, C.; Amould, I.; Prades, C.; Duverger, N.; Funke, H.; Assman, G.; Dinger, M.; Dean, M.; Chimini, G.; Santamarina-Fojo, S.; Fredrickson, D. S.; Denefle, P.; Bryan, H.; Brewer, H. B. Human ATP-binding cassette transporter 1 (ABC1): genomic organization and identification of the genetic defect in the original Tangier disease kindred. Proc. Natl. Acad. Sci. U.S.A. 1999, 96, 12685-12690.
8. Brooks-Wilson, A.; Marcil, M.; Clee, S. M.; Zhang, L. H.; Roomp, K.; van Dam, M.; Yu, L.; Brewer, C.; Collins, I. A.; Molhuizen, H. O.; Loubser, O.; Ouelette, B. F.; Fichter, K.; Ashboume-Excoffon, K. J.; Sensen, C. W.; Scherer, S.; Mott, S.; Denis, M.; Martindale, D.; Frohlich, J.; Morgan, K.; Koop, B.; Pimstone, S.; Kastelein, J. J.; Genest, J.; Hayden, M. R. Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat. Genet. 1999, 22, 336-345.
9. Bates, E. S.; Robey, R.; Knutsen, T.; Honjo, Y.; Litman, T.; Dean, M. New ABC transporters in multi-drug resistance. Emerging Ther. Targets 2000, 4, 561-580.
10. Gottesman, M. M.; Fojo, T.; Bates, S. E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat. Rev. Cancer 2002, 2, 48-58.
11. Schneider, E.; Paul, D.; Ivy, P.; Cowan, K. H. Multidrug resistance. Cancer Chemother. Biol. Response Modif. 1999, 18, 152-177.
12. Glavinas, H.; Krajcsi, P.; Cserepes, J.; Sarkadi, B. The role of ABC transporters in drug resistance, metabolism, and toxicity. Curr. Drug Delivery 2004, 1, 27-42.
13. Krishna, R.; Mayer, L. D. Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR, and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur. J. Pharm. Sci. 2000, 11, 265-283.
14. Leslie, E. M.; Deeley, R. G.; Cole, S. P. C. Multidrug resistance proteins: role of P-glycoprotein MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol. Appl. Pharmacol. 2005, 204, 216-237.
15. Nobili, S.; Landini, I.; Giglioni, B.; Mini, E. Pharmacological strategies for overcoming multidrug resistance. Curr. Drug Targets 2006, 7, 861-879.
16. Thomas, H.; Coley, H. M. Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting P-glycoprotein. Cancer Control 2003, 10, 159-165.
17. Pérez-Tomás, R. Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Curr. Med. Chem. 2006, 13, 1859-1876.
18. Teodori, E.; Dei, S.; Martelli, S.; Scapecchi, F.; Gualtieri, F. The functions and structure of ABC transporters: implications for the design of new inhibitors of P-gp and MRP1 to control multidrug resistance (MDR). Curr. Drug Targets 2006, 7, 893-909.
19. Avendano, C.; Menendez, J. C. Inhibitors of multidrug resistance to antitumor agents (MDR). Curr. Med. Chem. 2002, 9, 159-193.
20. Planting, A. S.; Sonneveld, P.; van der Gaast, A.; Sparreboom, A.; van der Burg, M. E.; Luyten, G. P.; de Leeuw, K.; de Boer-Dennert, M.; Wissel, P. S.; Jewell, R. C.; Paul, E. M.; Purvis, N. B.; Verweij, J. A phase I and pharmacologic study of the MDR converter GF120918 in combination with doxorubicin in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 2005, 55, 91-99.
21. Morschhauser, F.; Zinzani, P. L.; Burgess, M.; Sloots, L.; Bouafia, F.; Dumontet, C. Phase I/II trial of a P-glycoprotein inhibitor, Zosuquidar.3HCl trihydrochloride (LY335979), given orally in combination with the CHOP regimen in patients with non-Hodgkin's lymphoma. Leuk. Lymphoma 2007, 48, 708-715.
22. Modok, S.; Mellor, H. R.; Callaghan, R. Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer. Curr. Opin. Pharmacol. 2006, 6, 350-354.
23. Colabufo, N. A.; Berardi, F.; Perrone, R.; Rapposelli, S.; Digiacomo, M.; Balsamo, A. Arylmethyloxyphenyl derivatives: small molecules displaying P-glycoprotein inhibition. J. Med. Chem. 2006, 49, 6607-6613.
24. Polli, J. W.; Wring, S. A.; Humphreys, J. E.; Huang, L.; Morgan, J. B.; Webster, L. O.; Serabjit-Singh, C. S. Rational use of in vitro P-glycoprotein assays in drug discovery. J. Pharmacol. Exp. Ther. 2001, 299, 620-628.
25. Romera, J. L.; Cid, J. M.; Trabanco, A. A. Potassium iodide catalysed monoalkylation of anilines under microwave irradiation. Tetrahedron Lett. 2004, 45, 8797-8800.
26. Seelig, A.; Gatlik-Landwojtowicz, E. Inhibitors of multidrug efflux transporters: their membrane and protein interactions. Mini-Rev. Med. Chem. 2005, 5, 135-151.
27. Pleban, K.; Ecker, G. F. Inhibitors of P-glycoprotein-lead identification and optimisation. Mini-Rev. Med. Chem. 2005, 5, 153-163.
28. Balimane, P. V.; Chong, S. A combined cell based approach to identify P-glycoprotein substrates and inhibitors in a single assay. Int. J. Pharm. 2005, 301, 80-88.
29. Leopoldo, M.; Lacivita, E.; De Giorgio, P.; Colabufo, N. A.; Niso, M.; Berardi, F.; Perrone, R. Design, synthesis, and binding affinities of potential positron emission tomography (PET) ligands for visualization of brain dopamine D3 receptors. J. Med. Chem. 2006, 49, 358-365.
30. Rautio, J.; Humphreys, J. E.; Webster, L. O.; Balakrishnan, A.; Keogh, J. P.; Kunta, J. R.; Serabjit-Singh, J.; Polli, J. W. In vitro P-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Drug Metab. Dispos. 2006, 34, 786-792.
31. Kangas, L.; Grönroos, M.; Nieminem, A. L. Bioluminescence of cellular ATP: a new method for evaluating agents in vitro. Med. Biol. 1984, 62, 338-343.
32. Taub, M. E.; Podila, L.; Almeida, I. Functional assessment of multiple P-glycoprotein (P-gp) probe substrate: influence of cell line and modulator concentration on P-gp activity. Drug Metab. Dispos. 2005, 33, 1679-1687.
33. 1 antagonists in tumour cell lines. Naunyn-Schmiedeberg's Arch. Pharmacol. 2004, 370, 106-113.
34. GraphPad Prism Software, version for Windows; GraphPad Software, Inc.: San Diego, CA, 1998.