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Pregled bibliografske jedinice broj: 301146

Novel C-6 Fluorinated Acyclic Side Chain Pyrimidine Derivatives: Synthesis, H-1 and C-13 NMR Conformational Studies, and Antiviral and Cytostatic Evaluations


Prekupec, Svjetlana; Makuc, Damjan; Plavec, Janez; Šuman, Lidija; Kralj, Marijeta; Pavelić, Krešimir; Balzarini, Jan; De Clercq, Erik; Mintas, Mladen; Raić-Malić, Silvana
Novel C-6 Fluorinated Acyclic Side Chain Pyrimidine Derivatives: Synthesis, H-1 and C-13 NMR Conformational Studies, and Antiviral and Cytostatic Evaluations // Journal of Medicinal Chemistry, 50 (2007), 13; 3037-3045 (međunarodna recenzija, članak, znanstveni)


Naslov
Novel C-6 Fluorinated Acyclic Side Chain Pyrimidine Derivatives: Synthesis, H-1 and C-13 NMR Conformational Studies, and Antiviral and Cytostatic Evaluations

Autori
Prekupec, Svjetlana ; Makuc, Damjan ; Plavec, Janez ; Šuman, Lidija ; Kralj, Marijeta ; Pavelić, Krešimir ; Balzarini, Jan ; De Clercq, Erik ; Mintas, Mladen ; Raić-Malić, Silvana

Izvornik
Journal of Medicinal Chemistry (0022-2623) 50 (2007), 13; 3037-3045

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Fluoroalkylated pyrimidines; positron-emission tomography; NMR conformational analysis; antiviral and cytostatic activity evaluations

Sažetak
The synthetic route for introduction of a fluoroalkyl (7-12, 14), fluoroalkenyl (15 and 16), fluorophenylalkyl (17, 19, 20, and 22), and fluorophenylalkenyl (18, 21) side chain at C-6 of the pyrimidine involved the lithiation of the pyrimidine derivatives 3 and 3a and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with various electrophiles. Conformational properties of the novel fluorinated pyrimidine derivatives were assessed by the use of 1D difference NOE enhancements and C-F coupling constants. Compounds 4-22 were evaluated for their antiviral and cytostatic activities. Of all compounds evaluated, the 5-bromopyrimidine derivatives 5 and 6 showed the highest inhibitory activities. Among the series of fluoroalkylated pyrimidines, which is generally more active than the series of fluorophenylalkylated pyrimidines, compounds 8 and 14 displayed moderate cytostatic activities against the tested tumor cell lines. Moreover, compound 8 containing a 2-fluoromethylpropyl side chain expressed some but not highly specific activity against varicella-zoster virus (VZV). From C-6 fluorophenylalkylated pyrimidine derivatives, 17a and 21 showed a slight activity against cytomegalovirus (CMV), VZV, and Coxsackie B4 virus, respectively. Besides, compounds 17a and 21 showed no cytotoxic effect.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2393 - Molekularna obilježja miofibroblasta Dupuytrenove bolesti (Krešimir Pavelić, )
098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Marijeta Kralj, )
125-0982464-2922 - RAZVOJ NOVIH PROLIJEKOVA I LIJEKOVA PROTIV VIRUSA I RAKA (Mladen Mintas, )
125-0982464-2925 - Razvoj i primjena novih molekula u pozitron-emisijskoj tomografiji (PET) (Silvana Raić-Malić, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Uključenost u ostale bibliografske baze podataka:


  • Chemical Abstracts