Potent platelet-derived growth factor-β receptor (PDGF-βR) inhibitors: Synthesis and structure-activity relationships of 7-[3-(cyclohexylmethyl)ureido]-3-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl} quinoxalin-2(1H)-one derivatives

Chemical and Pharmaceutical Bulletin

Volumn 55, Issue 2, 2007, Pages 255-267

  Aoki, Katsuyuki ^a,c   Obata, Tatsuhiro ^a   Yamazaki, Yosuke ^a   Mori, Yoshikazu ^a,c   Hirokawa, Hiroko ^a   Koseki, Jun Ichi ^a   Hattori, Tomohisa ^a   Niitsu, Kazuaki ^a   Takeda, Shuichi ^a   Aburada, Masaki ^b   Miyamoto, Ken Ichi ^c  

^a TSUMURA AND CO   (Japan)

^b MUSASHINO UNIVERSITY   (Japan)

^c KANAZAWA UNIVERSITY   (Japan)

Author keywords

Friedel Crafts reaction; Platelet derived growth factor (PDGF); Pyrrolo 2,3 b pyridine; Quinoxalin 2 one; Tyrosine kinase inhibitor

Indexed keywords

2 CYCLOHEXYL N [3,4 DIHYDRO 2 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 3 OXOQUINOXALIN 6 YL]ACETAMIDE; 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 7 (3 MORPHOLINOUREIDO)QUINOXALIN 2(1H) ONE; 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 7 (3 OCTYLUREIDO)QUINOXALIN 2(1H) ONE; 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 7 (3 PENTYLUREIDO)QUINOXALIN 2(1H) ONE; 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 7 (3 PHENYLUREIDO)QUINOXALIN 2(1H) ONE; 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 7 (3 PROPYLUREIDO)QUINOXALIN 2(1H) ONE; 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 7 [3 (4PYRIDYLMETHYL)UREIDO]QUINOXALIN 2(1H) ONE; 3 CYCLOHEXYL N [3,4 DIHYDRO 2 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 3 OXOQUINOXALIN 6 YL]PROPANAMIDE; 3,4 DIHYDRO N [3,4 DIHYDRO 2 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 3 OXOQUINOXALIN 6 YL] 6,7 DIMETHOXYISOQUINOLINE 2(1H) CARBOXAMIDE; 4 [3 [2 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 3,4 DIHYDRO 3 OXOQUINOXALIN 6 YL]UREIDO]BUTYRIC ACID; 6 (3 CYCLOHEXYLMETHYLUREIDO) 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 6 FLUORO 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 7 (3 PENTYLUREIDO)QUINOXALIN 2(1H) ONE; 6 FLUORO 3 [1 (2 METHOXYETHYL) 1H PYRROLO[2,3 B]PYRIDIN 3 YL] 7 (3 PENTYLUREIDO)QUINOXALIN 2(1H) ONE; 6 FLUORO 3 [1 (3 MORPHOLINOPROPYL) 1H PYRROLO[2,3 B]PYRIDIN 3 YL] 7 (3 PENTYLUREIDO)QUINOXALIN 2(1H) ONE; 7 (3 BUTYLUREIDO) 3 (1 METHYL 1H PYRROLO[2,3-B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 CYCLOHEXYLMETHYL 2 OXOIMIDAZOLIDIN 1 YL) 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 CYCLOHEXYLMETHYLTHIOUREIDO) 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 CYCLOHEXYLMETHYLUREIDO) 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 2 QUINOLONE; 7 (3 CYCLOHEXYLMETHYLUREIDO) 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 CYCLOHEXYLMETHYLUREIDO) 3 (1 METHYLINDOLYL 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 CYCLOHEXYLMETHYLUREIDO) 6 FLUORO 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 CYCLOPENYLUREIDO) 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 CYCLOPROPYLMETYLUREIDO) 3 (1 METHYL 1H PYRROLO[2,3 B] PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 HEPTYLUREIDO) 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; 7 (3 HEXYLUREIDO) 3 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL)QUINOXALIN 2(1H) ONE; CYCLOHEXYLMETHYL [3,4 DIHYDRO 2 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 3 OXOQUINOXALIN 6 YL]CARBAMATE; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR INHIBITOR; QUINOXALINE DERIVATIVE; TERTBUTYL [3 [2 (1 METHYL 1H PYRROLO[2,3 B]PYRIDIN 3 YL) 3,4 DIHYDRO 3 OXOQUINOXALIN 6 YL]UREIDO]ACETATE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; STRUCTURE ACTIVITY RELATION;

CATALYSIS; ENZYME INHIBITORS; HEPATOCYTE GROWTH FACTOR; HUMANS; INHIBITORY CONCENTRATION 50; MANGANESE COMPOUNDS; OXIDATION-REDUCTION; OXIDES; PROTEIN-TYROSINE KINASES; QUINOXALINES; RECEPTOR, EPIDERMAL GROWTH FACTOR; RECEPTOR, IGF TYPE 1; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA; STRUCTURE-ACTIVITY RELATIONSHIP; TRIFLUOROACETIC ACID;

EID: 33846962171     PISSN: 00092363     EISSN: 13475223     Source Type: Journal    
DOI: 10.1248/cpb.55.255     Document Type: Article

References (48)

1. Heldin C. H., Westermark B., Wasteson A., Proc. Natl. Acad. Sci. U.S.A., 76, 3722-3726 (1979).
2. Heldin C. H., Westermark B., Cell Regul., 1, 555-566 (1990).
3. Heldin C. H., EMBO J., 11, 4251-4259 (1992).
4. Grotendrost G. R., Seppa H. E. J., Kleinman H. K., Martin G. R., Proc. Nat. Acad. Sci. U.S.A., 78, 3669-3672 (1981).
5. Wilcox J. N., Smith K. M., Williams L. T., Schwartz S. M., Gordon D., J. Clin. Invest., 82, 1134-1143 (1988).
6. Ross R., Masuda J., Raines E. W., Gown A. M., Katsuda S., Sasahara M., Malden L. T., Masuko H., Sato H., Science, 248, 1009-1012 (1990).
7. Ferns G. A. A., Raines E. W., Sprugel K. H., Motani A. S., Reidy M. A., Ross R., Science, 253, 1129-1132 (1991).
8. Jawien A., Bowen-Pope D. F., Lindner V., Schwartz S. M., Clowes A. W., J. Clin. Invest., 89, 507-511 (1992).
9. Bonner J. C., Lindroos P. M., Rice A. B., Moomaw C. R., Morgan D. L., Am. J. Physiol., 274, L72-80 (1998).
10. Friedman S. L., J. Biol. Chem., 275, 2247-2250 (2000).
11. Yasuhisa K., Medicinal Research Reviews, 23, 15-31 (2003).
12. Hart C. E., Forstrom J. W., Kelly J. D., Seifert R. A., Smith R. A., Ross R., Murray M. J., Bowen-Pope D. F., Science, 240, 1529-1531 (1988).
13. Ullrich A., Schlessinger J., Cell, 61, 203-212 (1990).
14. Heidaran M. A., Pierce J. H., Yu J.-C., Lombardi D., Artrip, J. E., Fleming T. P., Thomason A., Aaronson S. A., J. Biol. Chem., 266, 20232-20237 (1991).
15. Kanakaraj P., Raj S., Khan S. A., Bishayee S., Biochemistry, 30, 1761-1767 (1991).
16. Claesson-Welsh L., J. Biol. Chem., 269, 32023-32026 (1994).
17. Laird A. D., Vajkoczy P., Shawver L. K., Thurnher A., Liang C., Mohammadi M., Schlessinger J., Ulrich A., Hubbard S. R., Blake R. A., Fong A. T., Strawn L. M., Sun L., Tang C., Hawtin R., Tang F., Shemoy N., Hirth K. P., McMahon G., Cherrington J. M., Cancer Res., 60, 4152-4160 (2000).
18. Sun L., Tran N., Liang C., Hubbard S., Tang F., Lipson K., Schreck R., Zhou Y., McMahon G., Tang C., J. Med. Chem., 43, 2655-2663 (2000).
19. Sun L., Liang C., Shirazian S., Zhou Y., Miller T., Cui J., Fukuda J. Y., Chu J. Y., Nematalla A., Wang X., Chen H., Sistla A., Luu T. C., Tang F., Wei J., Tang C., J. Med. Chem., 46, 1116-1119 (2003).
20. Motzer R. J., Michaelson D., Redman B. G., Hudes G. R., Wilding G., Figlin R. A., Ginsberg M. S., Kim S. T., Baum C. M., DePrimo S. E., Li J. Z., Bello C. L., Theuer C. P., George D. J., Rini B. I., J. Clin. Oncol., 24, 1-3 (2006).
21. Myers M. R., He W., Hanney B., Setzer N., Maguire M. P., Zulli A., Bilder G., Galzcinski H., Amin D., Needle S., Spada A. P., Bioorg. Med. Chem. Lett., 13, 3091-3095 (2003).
22. He W., Myers M. R., Hanney B., Spada A. P., Bilder G., Galzcinski H., Amin D., Needle S., Page K., Jayyosi Z., Perrone M. H., Bioorg. Med. Chem. Lett., 13, 3097-3100 (2003).
23. Gazit A., Yee K., Uecker A., Bohmer F. D., Sjoblom T., Ostman A., Waltenberger J., Golomb G., Banai S., Heinrich M. C., Levitzki A., Bioorg. Med. Chem., 11, 2007-2018 (2003).
24. Dolle R. E., Dunn J. A., Bobko M., Singh B., Kuster J. E., Baizman E., Harris A. L., Sawutz D. G., Miller D., Wang S., Faltynek C. R., Xie W., Sarup J., Bode D. C., Pagani E. D., Silver P. J., J. Med. Chem., 37, 2627-2629 (1994).
25. Gazit A., App H., McMahon G., Chen J., Levitzki A., Bohmer F. D., J. Med. Chem., 39, 2170-2177 (1996).
26. Buchdunger E., Zimmermann J., Mett H., Meyer T., Muller M., Regenass U., Lydon N. B., Proc. Natl. Acad. Sci. U.S.A., 92, 2558-2562 (1995).
27. Manley P. W., Breitenstein W., Brueggen J., Cowan-Jacob S. W., Furet P., Mestan J., Meyer T., Bioorg. Med. Chem. Lett., 14, 5793-5797 (2004).
28. Matsuno K., Ichimura M., Nakajima T., Tahara K., Fujiwara S., Kase H., Ushiki J., Giese N. A., Pandey A., Scarborough R. M., Lokker N. A., Yu J.-C., Irie J., Tsukuda E., Ide S., Oda S., Nomoto Y., J. Med. Chem., 45, 3057-3066 (2002).
29. Pandey A., Volkots D. L., Seroogy J. M., Rose J. W., Yu J.-C., Lambing J. L., Hutchaleelaha A., Hollenbach S. J., Abe K., Giese N. A., Scarborough R. M., J. Med. Chem., 45, 3772-3793 (2002).
30. Matsuno K., Nakajima T., Ichimura M., Giese N. A., Yu J.-C., Lokker N. A., Ushiki J., Ide S., Oda S., Nomoto Y., J. Med. Chem., 45, 4513-4523 (2002).
31. Matsuno K., Seishi T., Nakajima T., Ichimura M., Giese N. A., Yu J.-C., Oda S., Nomoto Y., Bioorg. Med. Chem. Lett., 13, 3001-3004 (2003).
32. Matsuno K., Ushiki J., Seishi T., Ichimura M., Giese N. A., Yu J.-C., Takahashi S., Oda S., Nomoto Y., J. Med. Chem., 46, 4910-4925 (2003).
33. Heath J. A., Mehrotra M. M., Chi S., Yu J.-C., Hutchaleelaha A., Hollenbach S. J., Giese N. A., Scarborough R. M., Pandey A., Bioorg. Med. Chem. Lett., 14, 4867-4872 (2004).
34. Furuta T., Sakai T., Senga T., Osawa T., Kubo K., Shimizu T., Suzuki R., Yoshino T., Endo M., Miwa A., J. Med. Chem., 49, 2186-2192 (2006).
35. Mahboobi S., Teller S., Pongratz H., Hufsky H., Sellmer A., Botzki A., Uecker A., Beckers T., Baasner S., Schaechtele C., Ueberall F., Kassack M. U., Dove S., Boehmer F.-D., J. Med. Chem., 45, 1002-1018 (2002).
36. Kato S., Fujisawa A., Nanayama T., Jpn. Patent, JP2001089471 (2001).
37. Palmer B. D., Smaill J. B., Boyd M., Boschelli D. H., Doherty A. M., Hamby J. M., Khatana S. S., Kramer J. B., Kraker A. J., Panek R. L., Lu G. H., Dahring T. K., Winters R. T., Showalter H. D. H., Denny W. A., J. Med. Chem., 41, 5457-5465 (1998).
38. Palmer B. D., Kraker A. J., Hartl B. G., Panopoulos A. D., Panek R. L., Batley B. L., Lu G. H., Trumpp-Kallmeyer S., Showalter H. D. H., Denny W. A., J. Med. Chem., 42, 2373-2382 (1999).
39. Ho C. Y., Ludovici D. W., Maharoof U. S. M., Mei J., Sechler J. L., Tuman R. W., Strobel E. D., Andraka L., Yen H.-K., Leo G., Li J., Almond H., Lu H., DeVine A., Tominovich R. M., Baker J., Emanuel S., Gruninger R. H., Middleton S. A., Johnson D. L., Galemmo R. A., Jr., J. Med. Chem., 48, 8163-8173 (2005).
40. Dormidontov Y. P., Lapkin I. I., Lapteva V. V., Tr. Estestvenno-nauch. In-ta pri Perm. Un-te, 13, 170-173 (1975).
41. Bergstrand H., Karabelas K., Sjo P., PCT Int., WO9813368 A1 19980402 (1998).
42. Karabelas K., Lonn H., Sjo P., PCT Int. Appl., WO9946260 A1 19990916 (1999).
43. Karabelas K., Sjo P., PCT Int., WO9946264 A1 19990916 (1999).
44. Nixey Thomas, Tempest Paul, Hulme, Christopher., Tetrahedron Lett., 43, 1637-1639 (2002).
45. Bolotov V. V., Kovalenko S. N., Kovaleva S. V., Stepanenko V. I., Khimiya Geterotsiklicheskikh Soedinenii, 40, 211-213 (2004).
46. Chupakhin O. N., Sidorov E. O., Postovskii I. Y., Khimiya Geterotsiklicheskikh Soedinenii., 10, 1433-1434 (1975).
47. Cheeseman G. H. W., J. Chem. Soc., 1961, 1246-1251.
48. Cheeseman G. H. W., J. Chem. Soc., 1962, 1170-1176.