6-[1-(2,6-Difluorophenyl)ethyl]pyrimidinones Antagonize Cell Proliferation and Induce Cell Differentiation by Inhibiting (a Nontelomeric) Endogenous Reverse Transcriptase
transcriptase (endo-RT) in human differentiating cell systems to investigate their antiproliferative and cytodifferentiating activity. The two compounds significantly reduced cell proliferation and facilitated the morphological differentiation of cells. These results propose F(2)-DABOs as useful tools in preventive and/or curative therapy to counteract the loss of differentiation in dedifferentiating pathologies
Facile synthesis of the NNRTI microbicide MC-1220 and synthesis of its phosphoramidate prodrugs
作者:Yasser M. Loksha、Erik B. Pedersen、Paolo La Colla、Roberta Loddo
DOI:10.1039/c5ob02055g
日期:——
A facile and novelsyntheticroute to MC-1220 was achieved by condensation of 4,6-dichloro-N,N-5-trimethylpyrimidin-2-amine (1) with the sodium salt of 2,6-difluorophenylacetonitrile, followed by methylation and strong acidic hydrolysis. The prodrugs of MC-1220 were synthesized by reaction of chlorophosphoramidate derivatives (7a–e) or α-acetobromoglucose with the sodium salt of MC-1220. The stability
A Novel Synthetic Route for the Anti-HIV Drug MC-1220 and its Analogues
作者:Yasser M. Loksha、Daniel Globisch、Roberta Loddo、Gabriella Collu、Paolo La Colla、Erik B. Pedersen
DOI:10.1002/cmdc.201000244
日期:2010.11.8
Easy street: Herein we describe a novel and practical synthesis of the anti‐HIV compound MC‐1220. Through the use of inexpensive reagents and commercially available starting materials, MC‐1220 and itsanalogues are more easily accessed by a four‐step procedure involving a key reduction step.
Synthesis and Biological Properties of Novel 2-Aminopyrimidin-4(3<i>H</i>)-ones Highly Potent against HIV-1 Mutant Strains
作者:Antonello Mai、Marino Artico、Dante Rotili、Domenico Tarantino、Imma Clotet-Codina、Mercedes Armand-Ugón、Rino Ragno、Silvia Simeoni、Gianluca Sbardella、Maxim B. Nawrozkij、Alberta Samuele、Giovanni Maga、José A. Esté
DOI:10.1021/jm070811e
日期:2007.11.1
Following the disclosure of dihydro-alkoxy-, dihydro-alkylthio-, and dihydro-alkylamino-benzyl-oxopyrimidines (DABOs, S-DABOs, and NH-DABOs) as potent and selective anti-HIV-1 agents belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI) class, we report here the synthesis and biological evaluation of a novel series of DABOs bearing a NN-disubstituted amino group or a cyclic amine at the pyrimidine-C, position, a hydrogen atom or a small alkyl group at C-5 and/or at the benzylic position, and the favorable 2,6-difluorobenzyl moiety at the C-6 position (F,NN-DABOs). The new compounds were highly active up to the subnanomolar level against both wt HIV-1 and the Y181C mutant and at the submicromolar to nanomolar range against the K103N and Y188L mutant strains. Such derivatives were more potent than S-DABOs, NH-DABOs, and nevirapine and efavirenz were chosen as reference drugs. The higher inhibitor adaptability to the HIV- I RT non-nucleoside binding site (NNBS) may account for the higher inhibitory effect exerted by the new molecules against the mutated RTs.
Asymmetric Synthesis of Potential Precursors of the HIV Drug MC1220 and Its Analogues by Hydrogenation of (1-Arylvinyl)pyrimidines
作者:Yasser M. Loksha、Erik B. Pedersen
DOI:10.1002/jhet.3168
日期:2018.6
anti‐HIV‐1 activity, the possibility for asymmetric synthesis of its potential precursors is explored. Here, we investigateasymmetricreduction of the vinyl double bond of 6‐(1‐arylvinyl)pyrimidine derivatives to their corresponding ethylidene analogues. Catalysts with ligands bearing trivalent phosphorus ligating the soft metals rhodium(I), ruthenium(II), or iridium(I) are used for asymmetric reduction