Abstract
A facile general route was developed to synthesise new trisubstituted purin-8-one derivatives starting from cheap and readily available 5-bromouracil. These fused planar heterocycles present key hydrogen bond donating/accepting functionalities, making them interesting scaffolds for binding to biological targets.
Key words
purin-8-ones - fused-ring systems - nucleophilic aromatic substitution - ring-closure - microwave-assisted synthesis
References
1 Laufer SA.
Domeyer DM.
Scior TRF.
Albrecht W.
Hauser DRJ.
J. Med. Chem.
2005,
48:
710
2a Beck JP.
Arvanitis AG.
Curry MA.
Rescinito JT.
Fitzgerald LW.
Gilligan PJ.
Zaczek R.
Trainor GL.
Bioorg. Med. Chem. Lett.
1999,
9:
967
2b Bakthavatachalam R. inventors; PCT Int. Appl. WO, 01/83486.
3a Goodman MG.
Goodman JH.
J. Immunol.
1994,
130:
4081
3b Reitz AB.
Goodman MG.
Pope BL.
Argentieri DC.
Bell SC.
Burr LE.
Chourmouzis E.
Come J.
Goodman JH.
Klaubert DH.
Maryanoff BE.
McDonnell ME.
Rampulla MS.
Schott MR.
Chen R.
J. Med. Chem.
1994,
37:
3561
3c Reitz AB, Goodman MG, Chen R, and Maryanoff BE. inventors; U.S. Pat., 5786359.
4a Kurimoto A.
Ogino T.
Ichii S.
Isobe Y.
Tobe M.
Ogita H.
Takaku H.
Sajiki H.
Hirota K.
Kawakami H.
Bioorg. Med. Chem.
2003,
11:
5501
4b Hirota K.
Kazaoka K.
Sajiki H.
Bioorg. Med. Chem.
2003,
11:
2715
4c Hirota K.
Kazaoka K.
Niimoto I.
Sajiki H.
Org. Biomol. Chem.
2003,
1:
1354
5a Moravec J.
Krytof V.
Hanu J.
Havlíček L.
Moravcová D.
Fuksová K.
Kuzma M.
Lenobel R.
Otyepka M.
Strnad M.
Bioorg. Med. Chem. Lett.
2003,
13:
2993
5b Haesslein JL.
Jullian N.
Curr. Top. Med. Chem.
2002,
2:
1037
6a Rashidi MR.
Smith JA.
Clarke SE.
Beedham C.
Drug Metab. Dispos.
1997,
25:
805
6b Pochet S.
Marliere P.
C. R. Acad. Sci. Paris, Life Sciences/Biochemistry
1996,
319:
1
6c Krenitsky TA.
Hall WW.
De Miranda P.
Beauchamp LM.
Schaeffer HJ.
Whiteman PL.
Proc. Natl. Acad. Sci. U.S.A.
1984,
81:
3209
6d Rokos H.
Hakspiel B.
J. Carbohydr., Nucleosides, Nucleotides
1976,
3:
77
6e Dornow A.
Hinz E.
Chem. Ber.
1958,
91:
1834
7 Phillips AP.
J. Am. Chem. Soc.
1951,
73:
1061
8a Girault G.
Coustal S.
Rumpf P.
Bull. Soc. Chim. Fr.
1972,
2787
8b O’Brien DE.
Wayne Noell C.
Robins RK.
Cheng CC.
J. Med. Chem.
1966,
9:
121
9 The major by-product of the reaction proved to be the monochloro-product coming from the substitution at the most reactive position 4. It can be recovered during the purification and reused.
10a Sanghvi YS.
Larson SB.
Smee DF.
Revankar GR.
Robins RK.
Nucleosides Nucleotides
1991,
10:
1417
10b Cottam HB.
Larson SB.
Robins RK.
J. Heterocycl. Chem.
1987,
24:
821
11 Harayama T.
Fukushi H.
Ogawa K.
Aratani T.
Sonehara S.
Yoneda F.
Chem. Pharm. Bull.
1987,
35:
4977
12 Kazaoka K.
Sajiki H.
Hirota K.
Chem. Pharm. Bull.
2003,
51:
608
13 LCMS technique suggested that an acyl chloride intermediate was formed. Moreover, the 1 H NMR of this intermediate showed a split of the signal corresponding to the CH2 of the 5-benzylamino functionality, suggesting that the acyl chloride is fixed on this amino substituent.
14 Luo G.
Chen L.
Poindexter GS.
Tetrahedron Lett.
2002,
43:
5739
15 Ding S.
Gray NS.
Ding Q.
Schultz PG.
Tetrahedron Lett.
2001,
42:
8751
