Novel substituted quinazolines for potent EGFR tyrosine kinase inhibitors

Current Medicinal Chemistry

Volumn 18, Issue 7, 2011, Pages 943-963

  Cruz Lopez O ^a   Conejo Garcia A ^a   Nunez M C ^a   Kimatrai, M ^a   Garcia Rubino M E ^a   Morales, F ^a   Gomez Perez V ^a   Campos, J M ^a  

^a Servicio de Farmacia Hospitalaria   (Spain)

Author keywords

Antitumour; Bioisostere; EGFR; Erlotinib; Gefitinib; HER 2; Quinazoline; Tyrosine kinase inhibitor

Indexed keywords

3' ALKYNYL 4 ANILINOQUINAZOLINE DERIVATIVE; 4 ALKENYLQUINAZOLINE DERIVATIVE; 4 ALKYNYLQUINAZOLINE DERIVATIVE; 4 ANILINOQUINAZOLINE DERIVATIVE; 5,7 BIS ALKOXY ANILINOQUINAZOLINE DERIVATIVE; 6 ALKYNYL 4 ANILINOQUINAZOLINE DERIVATIVE; 6 AMINOMETHYL 4 ANILINOQUINAZOLINE DERIVATIVE; AMIDE; ANILINE DERIVATIVE; BIS ALKOXY ANILINOQUINAZOLINE DERIVATIVE; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR 4; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; GEFITINIB; IMIDAZOLE DERIVATIVE; IODOPHENOXYQUINAZOLINE DERIVATIVE; LAPATINIB; PIPERIDINE DERIVATIVE; PYRROLE DERIVATIVE; PYRROLIDINE DERIVATIVE; QUINAZOLINE DERIVATIVE; QUINAZOLINONE DERIVATIVE; TETRAHYDROFURAN; TETRAHYDROPYRAN DERIVATIVE; TRASTUZUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER INHIBITION; COLORECTAL CANCER; DRUG APPROVAL; DRUG DESIGN; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG RESEARCH; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME INHIBITION; HEAD AND NECK CARCINOMA; HUMAN; LUNG CANCER; NONHUMAN; OVARY CANCER; PROGNOSIS; PROSTATE CANCER; PROTEIN FAMILY; PROTEIN SYNTHESIS INHIBITION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

HUMANS; NEOPLASMS; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, ERBB-2; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 79952801118     PISSN: 09298673     EISSN: None     Source Type: Journal    
DOI: 10.2174/092986711794940824     Document Type: Article

References (88)

1. Johnston J.B.; Navaratman, S.; Pitz, M.W.; Maniate, J.M.; Wiechec, E.; Baust, H.; Gingerich, J.; Skliris, G.P.; Murphy, L.C.; Los, M. Targeting the EGFR pathway for cancer therapy. Curr. Med. Chem., 2006, 13, 3483-3492. (Pubitemid 44873742)
2. Nahta, R.; Esteva, F.J. Trastuzumab: Triumphs and tribulations. Oncogene, 2007, 26, 3637-3643. (Pubitemid 46842713)
3. Singer, C.F.; Köstler, W.J.; Hudelist, G. Predicting the efficacy of trastuzumab- based therapy in breast cancer: Current standards and future strategies. Biochim. Biophys. Acta, 2008, 1786, 105-113.
4. Baselga, J.; Swain, S.M. Novel anticancer targets: Revisiting ERBB2 and discovering ERBB3. Nat. Rev. Cancer, 2009, 9, 463-475.
5. Bose, R.; Zhang, X. The ErbB kinase domain: Structural perspectives into kinase activation and inhibition. Exp. Cell Res., 2009, 315, 649-658.
6. Hardie, G.; Hanks, S. The eukaryotic protein kinase superfamily. In The Protein Kinase Facts Book. Hardie, G.; Gibson, S.B., eds. Academic Press, London, Vol. 1, Chap. 2, 1995, pp. 7-47.
7. Pawson, T. Protein modules and signalling networks. Nature, 1995, 373, 573-580.
8. Levitzki, A.; Gazit, A. Tyrosine kinase inhibition: An approach to drug development. Science, 1995, 267, 1782-1788.
9. Blalock, W.L.; Weinstein-Oppenheimer, C.; Chang, F.; Hoytle, P.E.; Wang, X.Y.; Algate, P.A.; Franklin, R.A.; Oberhaus, S.M.; Steelman, L.S.; McCubrey, J.A. Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: Possible sites for intervention with anti-neoplastic drugs. Leukemia, 1999, 13, 1109-1166. (Pubitemid 29396575)
10. Catlett-Falcone, R.; Dalton, W.S.; Jove, R. STAT proteins as novel targets for cancer therapy. Signal transducer an activator of transcription. Curr. Opin. Oncol., 1999, 11, 490-496. (Pubitemid 29515894)
11. Cuadrado, A.; Bruder, J.T.; Heidaran, M.A.; App, H.; Rapp, U.R.; Aaronson, S.A. H-ras and raf-1 cooperate in transformation of NIH3T3 fibroblasts. Oncogene, 1993, 8, 2443-2448. (Pubitemid 23252373)
12. Sáez, R.; Chan, A.M.; Miki, T.; Aaronson, S.A. Oncogenic activation of human R-ras by point mutations analogous to those of prototype H-ras oncogenes. Oncogene, 1994, 9, 2977-2982. (Pubitemid 24296773)
13. Hunter, T. Oncoprotein networks. Cell, 1997, 88, 333-346. (Pubitemid 27131375)
14. Ullrich, A.; Schlessinger, J. Signal transduction by receptors with tyrosine kinase activity. Cell, 1990, 61, 203-212.
15. Supuran, C.T.; Scozzafava, A. Expert Opin. Ther. Patents, 2004, 141, 35- 53;
16. Yarden, Y.; Sliwkowski, M.X. Untangling the ErbB signalling network. Nat. Rev. Mol. Biol., 2001, 2, 127-137. (Pubitemid 33674041)
17. Cockerill, G.S.; Lackey, K.E. Small molecule inhibitors of the class 1 receptor tyrosine kinase family. Curr. Top. Med. Chem., 2002, 2, 1001-1010, and references therein.
18. Salomon, D.S.; Brandt, R.; Ciardiello, F.; Normanno, N. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit. Rev. Oncol. Hematol., 1995, 19, 183-232;
19. Woodburn, J.R. The epidermal growth factor receptor and its inhibition in cancer therapy. Pharmacol. Ther., 1999, 82, 241-250. (Pubitemid 29255919)
20. Kamath, S.; Buolamwini, J.K. Targeting EGFR and HER-2 receptor tyrosine kinases for cancer drug discovery and development. Med. Res. Rev., 2006, 26, 569-594. (Pubitemid 44230413)
21. Wakeling, A.E.; Guy, S.P.; Woodburn, J.R.; Ashton, S.E.; Curry, B.J. Barker, A.J.; Gibson, K.H. ZD1839 (Iressa): An orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res., 2002, 62, 5749-5754. (Pubitemid 35204731)
22. Moyer, J.D.; Barbacci, E.G.; Iwata, K.K.; Arnold, L.; Boman, B.; Cunningham, A.; Diorio, C.; Doty, J.; Morin, M.J.; Moyer, M.P.; Neveu, M.; Pollack, V.A.; Pustilnik, L.R.; Reynolds, M.M.; Slaon, D.; Theleman, A.; Miller, P. Induction of apoptosis and cell cycle arrest by CP-358,774, an inhibitor of epidermal growth factor receptor tyrosine kinase. Cancer Res., 1997, 57, 4838-4848. (Pubitemid 27468992)
23. Hirsch, F.R.; Witta, S. Biomarkers for prediction of sensitivity to EGFR inhibitors in non-small cell lung cancer. Curr. Opin. Oncol., 2005, 17, 118-122, and references therein; (Pubitemid 40516280)
24. Burris, H.A. Dual kinase inhibition in the treatment of breast cancer: Initial experience with the EGFR/ErbB-2 inhibitor lapatinib. Oncologist, 2004, 9, 10-15.
25. Johnston, S.R.D.; Leary, A. Lapatinib: A novel EGFR/HER2 tyrosine kinase inhibitor for cancer. Drugs Today, 2006, 7, 441-453; (Pubitemid 44221014)
26. Rusnak, D.W.; Lackey, K.; Affleck, K.; Wood, E.R.; Alligood, K.J.; Rhodes, N.; Keith, B.R.; Murray, D.M.; Knight, W.B.; Mullin, R.J.; Gilmer, T.M. The effects of the novel, reversible epidermal growth factor receptor/ErbB-2 tyrosine kinase inhibitor, GW2016, on the growth of human normal and tumorderived cell lines in vitro and in vivo. Mol. Cancer Ther., 2001, 1, 85-94.
27. Goldstein, N.I.; Prewett, M.; Zurklys, K.; Rockwell, P.; Mendelsohn, Biological efficacy of a chimeric antibody to the epidermal growth factor receptor in a human tumor xenograft model. J. Clin. Cancer Res., 1995, 1, 1311-1318.
28. Ciardiello, F.; De Vita, F.; Orditura, M.; Comunale, D.; Galizia, G. Cetuximab in the treatment of colorectal cancer. Future Oncol., 2005, 1, 173-181.
29. Cerea, G.; Ricotta, R.; Schiavetto, I.; Maugeri, M.R.; Sartore-Bianchi, A.; Moroni, M.; Artale, S.; Siena, S. Cetuximab for treatment of metastatic colorectal cancer. Ann. Oncol., 2006, 17 (Suppl 7), vii66-vii67. (Pubitemid 43985183)
30. Lilenbaum, R.C. The evolving role of cetuximab in non-small cell lung cancer. Clin. Cancer Res., 2006, 12 (14, Pt. 2), 4432s-4435s. (Pubitemid 44197194)
31. Burtness, B.; Goldwasser, M.A.; Flood, W.; Mattar, B.; Forastiere, A.A. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: An Eastern Cooperative Oncology Group study. J. Clin. Oncol., 2005, 23, 8646-8654. (Pubitemid 46211507)
32. Erratum in: J. Clin. Oncol., 2006, 24, 724.
33. Nahta, R.; Esteva, F.J. Herceptin: Mechanisms of action and resistance. Cancer Lett., 2006, 232, 123-138. (Pubitemid 43170962)
34. Morrison, C.; Zanagnolo, V.; Ramírez, N.; Cohn, D.E.; Kelbick, N.; Copeland, L.; Maxwell, L.G.; Fowler, J.M. HER-2 is an independent prognostic factor in endometrial cancer: Association with outcome in a large cohort of surgically staged patients. J. Clin. Oncol., 2006, 24, 2376-2385. (Pubitemid 46630670)
35. Erratum in: J. Clin. Oncol., 2006, 24, 3515.
36. Traxler, P. Protein tyrosine kinase inhibitors in cancer treatment. Exp. Opin. Ther. Patents, 1997, 7, 571-88; (Pubitemid 27278225)
37. Traxler, P. Tyrosine kinase inhibitors in cancer treatment (Part II). Exp. Opin. Ther. Patents, 1998, 8, 1599-1625. (Pubitemid 28546567)
38. Stamos, J.; Sliwkowski, M.X.; Eigenbrot, C. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4- anilinoquinazoline inhibitor. J. Biol. Chem., 2002, 277, 46265-46272. (Pubitemid 35417619)
39. Rusnak, D.W.; Affleck, K.; Cockerill, S.G.; Stubberfield, C.; Harris, R.; Page, M.; Smith, K.J.; Guntrip, S.B.; Carter, M.C.; Shaw, R.J.; Jowett, A.; Stables, J.; Topley, P.; Wood, E.R.; Brignola, P.S.; Kadwell, S.H.; Reep, B.R.; Mullin, R.J.; Alligood, K.J.; Keith, B.R.; Crosby, R.M.; Murray, D.M.; Knight, W.B.; Gilmer, T.M.; Lackey, K.E. The characterization of novel, dual ErbB-2/EGFR, tyrosine kinase inhibitors: Potential therapy for cancer. Cancer Res., 2001, 61, 7196-7203; (Pubitemid 32946515)
40. Zhang, Y.-M.; Cockerill, S.; Guntrip, S.B.; Rusnak, D.; Smith, K.; Vanderwall, D.; Wood, E.; Lackey, K. Synthesis and SAR of potent EGFR/erbB2 dual inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 111-114. (Pubitemid 38010204)
41. Hennequin, L.F.A.; Ballard, P.; Boyle, T., Delouvrié, B.; Ellston, R.P.A.; Halsall, C.T.; Harris, C.S.; Hudson, K.; Kendrew, J.; Pease, J.E.; Ross, H.S.; Smith, P.; Vincent, J.L. Novel 4-anilinoquinazolines with C-6 carbon-linked side chains: Synthesis and structure-activity relationship of a series of potent, orally active, EGF receptor tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett., 2006, 16, 2672-2676.
42. For a full description of synthesis and biological assays, see: (a) Hennequin, L.F.A.; Halsall, C.T. WO2005/02156, 2005;
43. Delouvrié, B.; Harris, C.S.; Hennequin, L.F.A.; Halsall, C.T.; Pease, J.E.; Smith, P.M. WO2005/075439, 2005.
44. Ballard, P.; Bradbury, R.H.; Harris, C.S.; Hennequin, L.F.A.; Hickinson, M.; Johnson, P.D.; Kettle, J.G.; Klinowska, T.; Leach, A.G.; Morgentin, R.; Pass, M.; Ogilvie, D.J.; Olivier, A.; Warin, N.; Williams, E.J. Inhibitors of epidermal growth factor receptor tyrosine kinase: Novel C-5 substituted anilinoquinazolines designed to target the ribose pocket. Bioorg. Med. Chem. Lett., 2006, 16, 1633-1637. (Pubitemid 43197536)
45. Liu, L.T.; Yuan, T.-T.; Liu, H.-H.; Chen, Sh.-F.; Wu, Y.-T. Synthesis and biological evaluation of substituted 6-alkynyl-4-anilinoquinazoline derivatives as potent EGFR inhibitors. Bioorg. Med. Chem. Lett., 2007, 17, 6373-6377. (Pubitemid 47559121)
46. Bridges, A.J.; Zhou, H.; Cody, D.R.; Rewcastle, G.W.; McMichael, A., Showalter, H.D.H.; Fry, D.W.; Kraker, A.J.; Denny, W.A. Tyrosine Kinase Inhibitors. 8. An Unusually Steep Structure-Activity Relationship for Analogues of 4-(3-Bromoanilino)-6,7-dimethoxyquinazoline (PD 153035), a Potent Inhibitor of the Epidermal Growth Factor Receptor. J. Med. Chem., 1996, 39, 267-276.
47. Barker, A.J.; Gibson, K.H.; Grundy, W.; Godfrey, A.A.; Barlow, J.J. Studies leading to the identification of ZD1839 (IRESSA): An orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg. Med. Chem. Lett., 2001, 11, 1911-1914 ; (Pubitemid 32675316)
48. Petrov, K.G.; Zhang, Y.-M.; Carter, M.; Cockerill, G.S.; Dickerson, S.; Gauthier, C.A.; Guo, Y.; Mook, R.A.Jr.; Rusnak, D.W.; Walker, A.L.; Wood, E.R.; Lackey, K.E. Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series. Bioorg. Med. Chem. Lett., 2006, 16, 4686-4691. (Pubitemid 44094055)
49. Bridges, A.J. The rationale and strategy used to develop a series of highly potent, irreversible, inhibitors of the epidermal growth factor receptor family of tyrosine kinases. Curr. Med. Chem., 1999, 6, 825-843. (Pubitemid 29422197)
50. For non-4-anilinoquinazoline EGFR-TK inhibitors, see: (a) Bridges, A.J.; Cody, D.R.; Zhou, H.; McMichael, A.; Fry, D.W. Enantioselective inhibition of the epidermal growth factor receptor tyrosine kinase by 4-(alphaphenethylamino) quinazolines. Bioorg. Med. Chem., 1995, 3, 1651-1656; (Pubitemid 26022441)
51. Gibson, K.H.; Grundy, W.; Godfrey, A.A.; Woodburn, J.R.; Ashton, S.E.; Curry, B.J.; Scarlett, L.; Barker, A.J.; Brown, D.S. Epidermal growth factor receptor tyrosine kinase: Structure-activity relationships and antitumour activity of novel quinazolines. Bioorg. Med. Chem., 1997, 7, 2723-2728; (Pubitemid 27472818)
52. Bouey-Bencteux, J.-P.; Loison, C.; Pommery, N.; Houssin, R.; Hénichart, J.- P. Synthesis and antiproliferative properties of 4-aminoquinazoline derivatives as inhibitors of EGF receptor-associated tyrosine kinase activity. Anti- Cancer Drug Des., 1998, 13, 893-922. (Pubitemid 29178764)
53. Kitano, Y.; Suzuki, T.; Kawahara, E.; Yamazahi, T. Synthesis and inhibitory activity of 4-alkynyl and 4-alkenylquinazolines: Identification of new scaffolds for potent EGFR tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett., 2007, 17, 5863-5867. (Pubitemid 47446219)
54. Fry, D.W.; Kraker, A.J.; McMichael, A.; Ambroso, L.A.; Nelson, J.M.; Leopold, W.R.; Conners, R.W.; Bridges, A.J. A specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science, 1994, 265, 1093-1095. (Pubitemid 24293076)
55. Hennion, G.F.; Hanzel, R.S. The alkylation of amines with t-acetylenic chlorides. Preparation of sterically hindered amines. J. Am. Chem. Soc., 1960, 82, 4908-4912.
56. Corey, E.J.; Fuchs, P.L. Tetrahedron Lett., 1972, 3769-3772;
57. For a review, see Eymery, F.; Iorga, B.; Savignac, P. The Usefulness of Phosphorus Compounds in Alkyne Synthesis. Synthesis, 2000, 185-213. (Pubitemid 30114754)
58. Frey, H.; Kaupp, G. 2-Propynylamines from 1,1-dibromo-1-alkenes. Synthesis, 1990, 931-934.
59. Imada, Y.; Yuasa, M.; Nakamura, I.; Murahashi, S.-I. Copper(I)-Catalyzed Amination of Propargyl Esters. Selective Synthesis of Propargylamines, 1- Alken-3-ylamines, and (Z)-Allylamines. J. Org. Chem., 1994, 59, 2282-2284. (Pubitemid 24193309)
60. Negishi, E.; Takahashi, T.; Van Horn, D.E.; Okukado, N. Nickel- or palladium- catalyzed cross coupling. 31. Palladium- or nickel-catalyzed reactions of alkenylmetals with unsaturated organic halides as a selective route to arylated alkenes and conjugated dienes: Scope, limitations, and mechanism. J. Am. Chem. Soc., 1987, 109, 2393-2401.
61. Compound 60d: Purohit, V.G.; Subramanian, R. Phase transfer-catalyzed alkylations of aldehydes and keto-esters. Chem. Ind., 1978, 731-732;
62. Compound 60n: Ghosez, L.; Cécile, F.; Frédéric, D.; Cuisinier, C.; Touillaux, R. Studies of palladium-catalyzed coupling reactions for preparation of hindered 3-arylpyrroles relevant to (-)-rhazinilam and its analogues. Can. J. Chem., 2001, 79, 1827-1839; (Pubitemid 34060184)
63. Compound 60o: Dority, J.A.Jr.; Earley, W.G.; Kumar, V.; Mallamo, J.P.; Miller, M.S.; Subramanyanm, C.U.S. Patent 5,569,655, 1996;
64. Compound 60p: Kira, M.A.; Aboul-Enein, M.N.; KorKor, M.I. The Vilsmeier-Haack Reaction. IV. Reaction of Phosphorus Oxychloride- Dimethylformamide with Semicarbazones. J. Heterocycl. Chem., 1970, 7, 25-6;
65. Hamatake, R.K.; Chen, H.; Raney, A.; Allan, M.J.; Lang, S. WO 2006033995.
66. Lorenzo, G.D.; Bianco, R.; Tortora, G.; Ciardiello, F. Involvement of growth factor receptors of the epidermal growth factor receptor family in prostate cancer development and progression to androgen independence. Clin. Prostate Cancer, 2003, 2, 50-57. (Pubitemid 37012422)
67. Telliez, A.; Desroses, M.; Pommery, N.; Briand, O.; Farce, A.; Laconde, G.; Lemoine, A.; Depreux, P.; Hénichart, J.-P. Derivatives of iressa, a specific epidermal growth factor receptor inhibitor, are powerful apoptosis inducers in PC3 prostatic cancer cells. ChemMedChem, 2007, 2, 318-332.
68. Hennequin, L.F.; Thomas, A.P.; Johnstone, C.; Stokes, E.S.; Plé, P.A.; Lohmann, J.J.; Ogilvie, D.J.; Dukes, M.; Wedge, S.R.; Curwen, J.O.; Kendrew, J.; Lambert-van der Brempt, C. Design and Structure-Activity Relationship of a New Class of Potent VEGF Receptor Tyrosine Kinase Inhibitors. J. Med. Chem., 1999, 42, 5369-5389. (Pubitemid 30036772)
69. Hennequin, L.F.; Stokes, E.S.; Thomas, A.P.; Johnstone, C.; Plé, P.A.; Ogilvie, D.J.; Dukes, M.; Wedge, S.R.; Kendrew, J.; Curwen, J.O. Novel 4- Anilinoquinazolines with C-7 Basic Side Chains: Design and Structure Activity Relationship of a Series of Potent, Orally Active, VEGF Receptor Tyrosine Kinase Inhibitors. J. Med. Chem., 2002, 45, 1300-1312. (Pubitemid 34263566)
70. Hunt, J.T.; Mitt, T.; Borzilleri, R.; Gullo-Brown, J.; Fargnoli, J.; Fink, B.; Han, W.C.; Mortillo, S.; Vite, G.; Waulet, B.; Wong, T.; Yu, C.; Zheng, X.; Bhide, R. Discovery of the pyrrolo[2,1-f][1,2,4]triazine nucleus as a new kinase inhibitor template. J. Med. Chem., 2004, 47, 4054-4059. (Pubitemid 38970966)
71. Wissner, A.; Floyd, M.B.; Jonhson, B.D.; Fraser, H.; Ingalls, C.; Nittoli, T.; Dushin, R.G.; Discafani, C.; Nilakantan, R.; Marini, J.; Ravi, M.; Cheung, K.; Tan, X.; Musto, S.; Annable, T.; Siegel, M.M.; Loganzo, F. 2- (Quinazolin-4-ylamino)-[1,4]benzoquinones as covalent-binding, irreversible inhibitors of the kinase domain of vascular endothelial growth factor receptor- 2. J. Med. Chem., 2005, 48, 7560-7581. (Pubitemid 41698798)
72. Miyamoto, H.; Altuwaijri, S.; Cai, E.M.; Messing, E.M.; Chang, C. Inhibition of the Akt, cyclooxygenase-2, and matrix metalloproteinase-9 pathways in combination with androgen deprivation therapy: Potential therapeutic approaches for prostate cancer. Mol. Carcinog., 2005, 44, 1-10. (Pubitemid 41216402)
73. Nakamura, H.; Kamamura, T.; Ishikura, M.; Biellmann, J. F. Synthesis of allenes via palladium-catalyzed hydrogen-transfer reactions: Propargylic amines as an allenyl anion equivalent. J. Am. Chem. Soc., 2004, 126, 5958-5959. (Pubitemid 38637952)
74. Nakamura, H.; Onagi, S.; Kamamura, T. Synthesis of heterocyclic allenes via palladium-catalyzed hydride-transfer reaction of propargylic amines. J. Org. Chem., 2005, 70, 2357-2360. (Pubitemid 40395183)
75. Nakamura, H.; Kamamura, T.; Onagi, S. 1,2-Bis(diphenylphosphino) carborane as a dual mode ligand for both the sonogashira coupling and hydridetransfer steps in palladium-catalyzed one-pot synthesis of allenes from aryl iodides. Org. Lett., 2004, 8, 2095-2098. (Pubitemid 43823619)
76. Nakamura, H.; Tashiro, S.; Kamamura, T. Synthesis of ene-allenes via palladium-catalyzed hydride-transfer reaction of propargylic amines under mild conditions. Tetrahedron Lett., 2005, 46, 8333-8336. (Pubitemid 41560860)
77. Nakamura, H.; Onagi, S. Synthesis and biological evaluation of allenic quinazolines using palladium-catalyzed hydride-transfer reaction. Tetrahedron Lett., 2006, 47, 2539-2542. (Pubitemid 43383935)
78. Ban, H.S.; Onagi, S.; Uno, M.; Nabeyama, W.; Nakamura, H. Allene as an Alternative Functional Group for Drug Design: Effect of C-C Multiple Bonds Conjugated with Quinazolines on the Inhibition of EGFR Tyrosine Kinase. ChemMedChem, 2008, 3, 1094-1103.
79. Hennequin, L.F.; Allen, J.; Breed, J.; Curwen, J.; Fennell, M.; Green, T.P.; Lambert van der Brempt, C.; Morgentin, R.; Norman, R.A.; Olivier, A.; Otterbein, L.; Plé, P.A.K Warin, N.; Costello, G. N-(5-Chloro-1,3- benzodioxol- 4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran- 4- yloxy)quinazolin-4-amine, a novel, highly selective, orally available, dualspecific c-Src/Abl kinase inhibitor. J. Med. Chem., 2006, 49, 6465-6488;
80. Barlaam, B.; Fennell, M.; Germain, H.; Green, T.; Hennequin, L.; Morgentin, R.; Olivier, A.; Plé, P.; Vautier, M.; Costello, G. New heterocyclic analogues of 4-(2-chloro-5-methoxyanilino)quinazolines as potent and selective c-Src kinase inhibitors. Bioorg. Med. Chem. Lett., 2005, 15, 5446-5449. (Pubitemid 41562967)
81. Ballard, P.; Bradbury, R.H.; Harris, C.S.; Hennequin, L.F.A.; Hickinson, M.; Johnson, P.D.; Kettle, J.G.; Klinowska, T.; Leach, A.G.; Morgentin, R.; Pass, M.; Ogilvie, D.J.; Olivier, A.; Waring, N.; Williams, E.J. Inhibitors of epidermal growth factor receptor tyrosine kinase: Novel C-5 substituted anilinoquinazolines designed to target the ribose pocket. Bioorg. Med. Chem. Lett., 2006, 16, 1633-1637. (Pubitemid 43197536)
82. Ballard, P.; Bradbury, R.H.; Hennequin, L.F.A.; Hickinson, D.M.; Johnson, P.D., Kettle, J.G.; Klinowska, T.; Morgentin, R.; Ogilvie, D.J.; Olivier, A. 5- Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase. Bioorg. Med. Chem. Lett., 2005, 15, 4226-4229. (Pubitemid 41187991)
83. Ballard, P.; Barlaam, B.C.; Bradbury, R.H.; Dishington, A.; Hennequin, L.F.A.; Kickinson, D.M.; Hollinsworth, I.M.; Kettle, J.G.; Klinowska, T.; Ogilvie, D.J.; Pearson, S.E.; Scott, J.S.; Suleman, A.; Whittaker, R.; Williams, E.J., Wood, R.; Wright, L. Bioorg. Med. Chem. Lett., 2007, 17, 6326-6329.
84. Barlaam, B.; Ballard, P.; Bradbury, R.H.; Ducray, R.; Germain, H.; Kickinson, D.M.; Hudson, K.; Kettle, J.G.; Klinowska, T.; Magnien, F.; Ogilvie, D.J.; Olivier, A.; Pearson, S.E.; Scott, J.S.; Suleman, A.; Trigwell, C.B.; Vautier, M.; Whittaker, R.D.; Wood, R. A new series of neutral 5-substituted 4-anilinoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase. Bioorg. Med. Chem. Lett., 2008, 18, 674-678.
85. Baselga, J.; Norton, L.; Albanell, J.; Kim, Y.M.; Mendelsohn, J. Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res., 1998, 58, 2825-2831; (Pubitemid 28311914)
86. Erratum in: Cancer Res., 1999, 59, 2020.
87. Lüth, A.; Löwe, W. Syntheses of 4-(indole-3-yl)quinazolines. A new class of epidermal growth factor receptor tyrosine kinase inhibitors. Eur. J. Med. Chem., 2008, 43, 1478-1488. (Pubitemid 351885214)
88. Sawyers, C. Targeted cancer therapy. Nature (Lond.), 2004, 432, 294-297. (Pubitemid 39551656)