Potent and selective inhibitors of PDGF receptor phosphorylation. 2. Synthesis, structure activity relationship, improvement of aqueous solubility, and biological effects of 4-[4-(N-substituted (thio)carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazoline derivatives

Journal of Medicinal Chemistry

Volumn 45, Issue 20, 2002, Pages 4513-4523

  Matsuno, Kenji ^a   Nakajima, Takao ^a   Ichimura, Michio ^a   Giese, Neill A ^b   Yu, Jin Chen ^b   Lokker, Nathalie A ^b   Ushiki, Junko ^a   Ide, Shin ichi ^a   Oda, Shoji ^a   Nomoto, Yuji ^a  

^a KYOWA HAKKO KOGYO CO LTD   (Japan)

^b MILLENNIUM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(1 PIPERAZINYL) 6,7 DIMETHOXYQUINAZOLINE DERIVATIVE; 4 (6,7 DIMETHOXY 4 QUINAZOLINYL) N (3 PICOLYL) 1 PIPERAZINETHIOCARBOXAMIDE; 4 (6,7 DIMETHOXY 4 QUINAZOLINYL) N (4 METHOXYBENZYL) 1 PIPERAZINECARBOXAMIDE; 4 (6,7 DIMETHOXY 4 QUINAZOLINYL) N (4 METHOXYBENZYL) 1 PIPERAZINETHIOCARBOXAMIDE; 4 (6,7 DIMETHOXY 4 QUINAZOLINYL) N FURFURYL 1 PIPERAZINETHIOCARBOXAMIDE; 4 (6,7 DIMETHOXYQUINAZOLINYL) N (3 THIENYL) 1 PIPERAZINECARBOXAMIDE; CT 52923; GUANIDINE DERIVATIVE; INHIBITOR PROTEIN; KN 1022; KN 734; N (4 CHLOROBENZYL) 4 (6,7 DIMETHOXY 4 QUINAZOLINYL) 1 PIPERAZINETHIOCARBOXAMIDE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR INHIBITOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; AQUEOUS SOLUTION; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG EFFECT; DRUG HALF LIFE; DRUG SOLUBILITY; DRUG SYNTHESIS; NONHUMAN; PHOSPHORYLATION; RAT; RESTENOSIS; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANIMALS; CAROTID ARTERIES; PHOSPHORYLATION; PIPERAZINES; PROTEIN KINASE INHIBITORS; QUINAZOLINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA; SOLUBILITY; STRUCTURE-ACTIVITY RELATIONSHIP; THIOCARBAMATES; TUNICA INTIMA; WATER;

EID: 0037179623     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm0201114     Document Type: Article

References (37)

1. Fretto, L. J.; Snape, A. J.; Tomlinson, J. E.; Seroogy, J. J.; Wolf, D. L.; LaRochelle, W. J.; Giese, N. A. Mechanism of platelet-derived growth factor (PDGF) AA, AB, and BB binding to alpha and beta PDGF receptor. J. Biol. Chem. 1993, 268, 3625-3631.
2. Heldin, C. H.; Ostman, A.; Eriksson, A.; Siegbahn, A.; Claesson-Welsh, L.; Westermark, B. Platelet-derived growth factor: isoform-specific signaling via heterodimeric or homodimeric receptor complexes. Kidney Int. 1992, 41, 571-574.
3. Herren, B.; Rooney, B.; Weyer, K. A.; Iberg, N.; Schmid, G.; Pech, M. Dimerization of extracellular domains of platelet-derived growth factor receptors. A revised model of receptor-ligand interaction. J. Biol. Chem. 1993, 268, 15088-15095.
4. Stoddard, B. L.; Biemann, H. P.; Koshland, D. E., Jr. Receptors and transmembrane signaling. Cold Spring Harb. Syrup. Quantum Biol. 1992, 57, 1-15.
5. Bonner, J. C.; Lindroos, P. M.; Rice, A. B.; Moomaw, C. R.; Morgan, D. L. Induction of PDGF receptor-alpha in rat myofibroblasts during pulmonary fibrogenesis in vivo. Am. J. Physiol. 1998, 274, L72-80.
6. Friedman, S. L. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J. Biol. Chem. 2000, 275, 2247-2250.
7. Gesualdo, L.; Pinzani, M.; Floriano, J. J.; Hassan, M. O.; Nagy, N. U.; Schena, F. P.; Emancipator, S. N.; Abboud, H. E. Platelet-derived growth factor expression in mesangial proliferative glomerulonephritis. Lab. Invest. 1991, 65, 160-167.
8. Heldin, C. H.; Westermark, B. Platelet-derived growth factor: mechanism of action and possible in vivo function. Cell. Regul. 1990, 1, 555-566.
9. Iida, H.; Seifert, R.; Alpers, C. E.; Gronwald, R. G.; Phillips, P. E.; Pritzl, P.; Gordon, K.; Gown, A. M.; Ross, R.; Bowen-Pope, D. F.; et al. Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat. Proc. Natl. Acad. Sci. U.S.A. 1991, 88, 6560-6564.
10. Johnson, R. J.; Raines, E. W.; Floege, J.; Yoshimura, A.; Pritzl, P.; Alpers, C.; Ross, R. Inhibition of mesangial cell proliferation and matrix expansion in glomerulonephritis in the rat by antibody to platelet-derived growth factor. J. Exp. Med. 1992, 175, 1413-1416.
11. Rice, A. B.; Moomaw, C. R.; Morgan, D. L.; Bonner, J. C. Specific inhibitors of platelet-derived growth factor or epidermal growth factor receptor tyrosine kinase reduce pulmonary fibrosis in rats. Am. J. Pathol. 1999, 155, 213-221.
12. Ross, R.; Masuda, J.; Raines, E. W.; Gown, A. M.; Katsuda, S.; Sasahara, M.; Malden, L. T.; Masuko, H.; Sato, H. Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science 1990, 248, 1009-1012.
13. Wilcox, J. N.; Smith, K. M.; Williams, L. T.; Schwartz, S. M.; Gordon, D. Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization. J. Clin. Invest. 1988, 82, 1134-1143.
14. Wong, L.; Yamasaki, G.; Johnson, R. J.; Friedman, S. L. Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture. J. Clin. Invest. 1994, 94, 1563-1569.
15. Yagi, M.; Kato, S.; Kobayashi, Y.; Kobayashi, N.; Iinuma, N.; Nakamura, K.; Kubo, K.; Ohyama, S.; Murooka, H.; Shimizu, T.; Nishitoba, T.; Osawa, T.; Nagano, N. Beneficial effects of a novel inhibitor of platelet-derived growth factor receptor autophosphorylation in the rat with mesangial proliferative glomerulonephritis. Gen. Pharmacol. 1998, 31, 765-773.
16. Bilder, G.; Wentz, T.; Leadley, R.; Amin, D.; Byan, L.; O'Conner, B.; Needle, S.; Galczenski, H.; Bostwick, J.; Kasiewski, C.; Myers, M.; Spada, A.; Merkel, L.; Ly, C.; Persons, P.; Page, K.; Perrone, M.; Dunwiddie, C. Restenosis following angioplasty in the swine coronary artery is inhibited by an orally active PDGF-receptor tyrosine kinase inhibitor, RPR101511A. Circulation 1999, 99, 3292-3299.
17. Ferns, G. A.; Raines, E. W.; Sprugel, K. H.; Motani, A. S.; Reidy, M. A.; Ross, R. Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science 1991, 253, 1129-1132.
18. Giese, N. A.; Marijianowski, M. M.; McCook, O.; Hancock, A.; Ramakrishnan, V.; Fretto, L. J.; Chen, C.; Kelly, A. B.; Koziol, J. A.; Wilcox, J. N.; Hanson, S. R. The role of alpha and beta platelet-derived growth factor receptor in the vascular response to injury in nonhuman primates. Arterioscler. Thromb. Vasc. Biol. 1999, 19, 900-909.
19. Hart, C. E.; Kraiss, L. W.; Vergel, S.; Gilbertson, D.; Kenagy, R.; Kirkman, T.; Crandall, D. L.; Tickle, S.; Finney, H.; Yarranton, G.; Clowes, A. W. PDGFbeta receptor blockade inhibits intimal hyperplasia in the baboon. Circulation 1999, 99, 564-569.
20. Sirois, M. G.; Simons, M.; Edelman, E. R. Antisense oligonucleotide inhibition of PDGFR-beta receptor subunit expression directs suppression of intimal thickening. Circulation 1997, 95, 669-676.
21. Matsuno, K.; Ichimura, M.; Nomoto, Y.; Fujiwara, S.; Ide, S.-i.; Tsukuda, E.; Irie, J.; Oda, S. PCT Int. Appl. No. WO9814431, April 9, 1998; Chem. Abstr. 1998, 128, 257447.
22. Matsuno, K.; Nakajima, T.; Tahara, K.; Seishi, T.; Fujiwara, S.; Ichimura, M.; Giese, N. A.; Yu, J.-C.; Irie, J.; Tsukuda, E.; Ide, S.-i.; Oda, S.; Nomoto, Y. Synthesis and structure activity relationships of PDGF receptor phosphorylation inhibitor-1. In Proceedings of the 18th Symposium on Medicinal Chemistry, 7th Annual Meeting of Division of Medicinal Chemistry, The Pharmaceutical Society of Japan, Kyoto, Japan, Nov 25-27, 1998; The Pharmaceutical Society of Japan: Tokyo, 1998; p 2P-05.
23. Matsuno K.; Nakajima, T.; Tahara, T.; Fujiwara, S.; Ichimura, M.; Giese, N. A.; Yu, J.-C.; Irie, J.; Tsukuda, E.; Ide, S.-i.; Oda, S.; Nomoto, Y. Selective inhibitor of PDGF receptor phosphorylation. Synthesis, structure activity relationships and biological effects. In Proceedings of the 217th National Meeting of the American Chemical Society, Anaheim, CA, Mar 21-25, 1999; American Chemical Society: Washington, DC, 1999; p MEDI 61.
24. Matsuno, K.; Ichimura, M.; Nakajima, T.; Tahara, K.; Fujiwara, S.; Kase, H.; Giese, N. A.; Pandey, A.; Scarborough, R. M.; Yu, J.-C.; Lokker, N. A.; Irie, J.; Tsukuda, E.; Ide, S.-i.; Oda, S.; Nomoto, Y. Potent and selective inhibitors of PDGF receptor phosphorylation. 1. synthesis and structure activity relationship of a new class of quinazoline derivatives. J. Med Chem. 2002, 45, 3057-3066.
25. Cronin, T. H.; Hess, H.-J. E. South African Patent Appl. No. 676512, October 31, 1967; Chem. Abstr. 1969, 70, 68419.
26. Freer, R.; McKillop, A. Synthesis of symmmetrical and unsymmmetrical ureas using unsymmetrical diaryl carbonates. Synth. Commun. 1996, 26, 331-349.
27. Cronin, T. H.; Hess, H.-J. E. U.S. Patent No. 3814760, January 04, 1974; Chem. Abstr. 1974, 81, 105553h.
28. Gizycki, U. v.; Oertel, G. Anellierte 1,3,5-Triazin-2,4-dione als Dimere Heterocyclischer Isocyanate. Angew. Chem. 1968, 9, 363-364.
29. Binder, D.; Habison, G.; Noe, C. R. Eine einfache Herstellungsmethode für 2-Aminothiophene. Synthesis 1977, 255-258.
30. Yu, J.-C.; Lokker, N.; Hollenbach, S.; Apatira, M.; Li, J.; Betz, A.; Sedlock, D.; Oda, S.; Nomoto, Y.; Matsuno, K.; Ide, S.; Tsukuda, E.; Giese, N. A efficacy of the novel selective platelet-derived growth factor receptor antagonist CT52923 on cellular proliferation, migration, and suppression of neointima following vascular injury. J. Pharm. Exp. Ther. 2001, 298, 1172-1178.
31. Qiu, F. H.; Ray, P.; Brown, K.; Barker, P. E.; Jhanwar, S.; Ruddle, F. H.; Besmer, P. Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. Embo. J. 1988, 7, 1003-1011.
32. Fambrough, D.; McClure, K.; Kazlauskas, A.; Lander, E. S. Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes. Cell 1999, 97, 727-741.
33. Lokker, N. A.; Sullivan, C. M.; Hollenbach, S. J.; Israel, M. A.; Giese, N. A. Platelet-derived growth factor (PDGF) autocrine signaling regulates survival and mitogenic pathways in glioblastoma cells: evidence that the novel PDGF-C and PDGF-D ligands may play a role in the development of brain tumors. Cancer Res. 2002, 62, 3729-3735.
34. Giese, N. A.; Lokker, N. A.; Yu, J.-C.; Matsuno, K.; Ichimura, M.; Oda, S.; Scarborough, R. M.; Pandey, A. Development of antagonists of the platelet-derived growth factor receptor family. Oncology Spectrums 2001, 2, 550-556.
35. Hirota, S.; Isozaki, K.; Moriyama, Y.; Hashimoto, K.; Nishida, T.; Ishiguro, S.; Kawano, K.; Hanada, M.; Kurata, A.; Takeda, M.; Muhammad, T. G.; Matsuzawa, Y.; Kanakura, Y.; Shinomura, Y.; Kitamura, Y. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998, 279, 577-580.
36. Lux, M. L.; Rubin, B. P.; Biase, T. L.; Chen, C. J.; Maclure, T.; Demitri, G.; Xiao, S.; Singer, S.; Fletcher, C. D.; Fletcher, J. A. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am. J. Pathol. 2000, 156, 791-795.
37. Joensuu, H.; Roberts, P. J.; Sarlomo-Rikala, M.; Andersson, L. C.; Tervahartiala, P.; Tuveson, D.; Silberman, S.; Capdeville, R.; Dimitrijevic, S.; Drucker, B.; Demetri, G. Effect of the tyrosine kinase inhibitor ST1571 in a patient with a metastatic gastrointestinal stromal tumor. N. Engl. J. Med. 2001, 344, 1052-1056.