136105-79-8Relevant articles and documents
Synthesis and anti-HIV-1 activity of new fluoro-HEPT analogues: An investigation on fluoro versus hydroxy substituents
Loksha, Yasser M.,Pedersen, Erik B.,Loddo, Roberta,La Colla, Paolo
, p. 366 - 371 (2012/01/11)
Coupling of 6-benzyl-5-hydroxymethyluracil (1) with formaldehyde acetals followed by fluorination using (diethylamino)sulfur trifluoride (DAST) afforded 1-alkenyloxymethyl and 1-propargyloxymethyl 5-fluoromethyl-6-benzyluracils 3a-c. 6-(3,5-Dimethylbenzyl)-5-ethyl-1-[(2-fluoroethoxy)methyl]pyrimidine-2,4(1H,3H)- dione (6) was synthesized by fluorination of the corresponding hydroxy derivative 5. Sonogoshira reaction was performed on 6-(3,5-dimethylbenzyl)-5- ethyl-1-(4-iodobenzyl)uracil (7) with propargyl alcohol to afford 8 which was fluorinated to give the fluoro propargyl derivative 9. Compound 7 was synthesized by N1-alkylation of the corresponding uracil. Significant activity was found against HIV-1 except for compounds with 5-hydroxymethyl and 5-fluoromethyl substituents. Copyright
Synthesis and antiviral activity of 6-benzyl analogs of 1-[(2- hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) as potent and selective anti-HIV-1 agents
Tanaka,Takashima,Ubasawa,Sekiya,Inouye,Baba,Shigeta,Walker,De Clercq,Miyasaka
, p. 2860 - 2865 (2007/10/02)
Several 6-benzyl analogs of 1-[(2-hydroxyethoxy)methyl]-6- (phenylthio)thymine (1; HEPT) were synthesized and evaluated for their anti- HIV-1 activity. LDA (lithium diisopropylamide) lithiation of 5-ethyluracil derivatives 7 and 8 and subsequent reaction with an aryl aldehyde gave 6- (arylhydroxymethyl)-5-ethyluracil derivatives 9-12. 6-(Arylhydroxymethyl)-5- isopropyluracil derivatives 15-18 were prepared from the 5-isopropyl-2- thiouracil derivatives 13 and 14 by the above procedure following oxidative hydrolysis of the thione. Preparation of the target 5-alkyl-1-(alkoxymethyl)- 6-benzyluracil derivatives 27-34 was carried out by acetylation of 9-14 followed by Pd-catalyzed hydrogenolysis. The 1-butyl- (37 and 39) and 1-(2- methoxyethyl)- (38 and 40) 5-alkyl-6-benzyluracils were synthesized by 1- alkylation of the 3-phenacyl derivatives 35 and 36 with alkyl halides followed by deprotection of the 3-phenacyl group. Compounds synthesized in this study inhibited HIV-1 replication in MT-4 cells in the submicromolar to nanomolar concentration range. From this series of compounds, 6-benzyl-1- (ethoxymethyl)-5-isopropyluracil (33) was selected for clinical evaluation.
