Efficient synthesis and biological evaluation of some 2,4-diamino-furo[2,3-d]pyrimidine derivatives.
The carbodiimides 2, obtained from aza-Wittig reactions of iminophosphorane 1 with aromatic isocyanates, reacted with ammonia to give ethyl 3,4-dihydro-6-methyl-4-oxo-2-arylamino-furo[2,3-d]pyrimidine-5-carboxylate 3. Further reaction of 3 with POCl(3) and various amines generated ethyl 4-alkylamino-2-arylamino-6-methyl-furo[2,3-d]pyrimidine-5-carboxylate 5 in good yields. Their structures were confirmed by (1)H NMR, EI-Ms, IR and elemental analysis. Compound 5b was further analyzed by single crystal X-ray diffraction. Compound 5 exhibited cytotoxicity against two lung cancer cell lines. For example, compound 5a showed the best inhibition activities against A459 with IC(50) 0.8μM.
Hu
Yang-Gen
YG
Institute of Medicinal Chemistry, Hubei Medical University, Shiyan 442000, China; Department of Pharmacy, Taihe Hospital of Hubei Medical University, Shiyan 442000, China. huyangg111@yahoo.com.cn
Wang
Yan
Y
Du
Shi-Ming
SM
Chen
Xiao-Bao
XB
Ding
Ming-Wu
MW
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008175:Lung Neoplasms / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D005663:Furans; D007202:Indicators and Reagents; D011743:Pyrimidines