Abstract
Some 4-N -(3′- or 4′-substituted-phenyl)amino-6,7-dimethoxyquinazolines and the corresponding unsubstituted compounds were synthesized from 2-amino-4,5-dimethoxybenzoic acid and the appropriate substituted anilines. Other related quinazolines or their synthetic intermediates were also obtained. A large number of the described quinazolines are new compounds, while the remaining were prepared by a more efficient procedure. The main goal for the synthesis of these compounds comes from the fact that the 4-anilinoquinazoline pharmacophore is an important unit, which is found among the ATP-competitive inhibitors of several protein kinase enzymes.
Key words
4-anilinoquinazolines - quinazolinones - ATP-inhibitors
References
1 Palmer BD.
Trumpp-Kallmeyer S.
Fry DW.
Nelson JM.
Showalter HDH.
Denny WA.
J. Med. Chem.
1997,
40:
1519
2 Thompson AM.
Murray DK.
Elliot WL.
Fry DW.
Nelson JA.
Showalter HDH.
Roberts BJ.
Vincent PW.
Denny WA.
J. Med. Chem.
1997,
40:
3915
3 Fry DW.
Kraber AJ.
McMichael A.
Ambroso LA.
Nelson JM.
Leopold WR.
Connors RW.
Bridges AJ.
Science
1994,
265:
1093
4 Baselga J.
Averbuch SD.
Drugs
2000,
60:
33
5 Ciardiello F.
Drugs
2000,
60:
25
6 Rewcastle GW.
Denny WA.
Bridges AJ.
Zhou H.
Cody DR.
McMichael A.
Fry DW.
J. Med. Chem.
1995,
38:
3482
7 Bridges AJ.
Zhou H.
Cody DR.
Rewcastle GW.
McMichael A.
Fry DW.
Denny WA.
J. Med. Chem.
1996,
39:
267
8 Rewcastle GW.
Murray DK.
Elliot WL.
Fry DW.
Howard CT.
Nelson JA.
Roberts BJ.
Vincent PW.
Showalter HDH.
Winters RT.
Denny WA.
J. Med. Chem.
1998,
41:
742
9 Fry DW.
Pharmacol. Ther.
1999,
82:
207
10 Levitzki A.
Pharmacol. Ther.
1999,
82:
231
11 Fry DW.
Annu. Rep. Med. Chem.
1996,
31:
151
12 Rewcastle GW.
Denny WA.
Showalter HDH.
Curr. Org. Chem.
2000,
4:
679
13 Szczepankiewicz W.
Suwi J.
Bujok R.
Tetrahedron
2000,
56:
9343
14 Tomisek AJ.
Christensen BE.
J. Am. Chem. Soc.
1948,
70:
2423
15 Zentmyer DT.
Wagner EC.
J. Org. Chem.
1949,
14:
967
16 Errede LA.
Oien HT.
Yarian DR.
J. Org. Chem.
1977,
42:
12
17 Yale HL.
J. Am. Chem. Soc.
1955,
75:
675
18 Girgis NS.
Mφller J.
Pedersen EB.
Chem. Scrip.
1986,
26:
617
19 Taylor EC.
Ravindranathan RV.
J. Org. Chem.
1962,
27:
2622
20 Loakes D.
Brown DM.
Salisbury SA.
J. Chem. Soc., Perkin Trans. 1
1999,
1333
21 Veldhuyzen WF.
Shallop AJ.
Jones RA.
Rokita SE.
J. Am. Chem. Soc.
2001,
123:
11126
22 Franchini, K., Faculty of Medical Sciences, State University of Campinas, personal communication.
23 Nishikawa S.
Maki S.
Nishikimi Y.
Kumazawa Z.
Kashimura N.
Biosci. Biotech. Biochem.
1994,
58:
1709
24 Hennequin LF.
Thomas AP.
Johnstone C.
Stokes ESE.
Plé PA.
Lohmann JJM.
Ogilvie DJ.
Dukes M.
Wedge SR.
Curwen JO.
Kendrew J.
Brempt CL.
J. Med. Chem.
1999,
42:
5369
