Synthesis and Anti‐HIV‐1 Evaluation of Some Novel MC‐1220 Analogs as Non‐Nucleoside Reverse Transcriptase Inhibitors

Abstract

Some novel MC-1220 analogs were synthesized by condensation of 4,6-dichloro-N-methylpyrimidin-2-amine derivatives (1a,b and 15) and/or 4-chloro-6-methoxy-N,N,5-trimethylpyrimidin-2-amine (2a) with the sodium salt of 2,6-difluorophenylacetonitrile followed by treatment with aqueous sodium hydroxide in methanol, alkylation, reduction, halogenation, and/or acidic hydrolysis. All synthesized compounds were evaluated for their activity against HIV-1. The most active compound in this study was compound 7, which showed activity against HIV-1 comparable to that of MC-1220. The only difference in structure between compound 7 and MC-1220 is a fluoro atom instead of a CH3 group.

Pharmacological Perspectives of 2‐alkoxy‐3‐Cyanopyridine Scaffolds: An Up‐to‐Date Review

“…Nucleoside antiviral medications, commonly used for treating viral diseases like HIV, have been significantly developed, but non-nucleoside analogs have emerged as highly effective antiviral agents. [146] A number of nucleoside and non-nucleoside pyridine analogs 75 a-j (Figure 20) were reported and analyzed by Ibrahim et al based on the facts to test their in vitro antiviral abilities against different DNA-and RNA-virus types. [147] It was shown that the majority of active chemicals are more selective in their inhibition of DNA-virus replication than RNA-virus replication.…”

“…Nucleoside antiviral medications, commonly used for treating viral diseases like HIV, have been significantly developed, but non‐nucleoside analogs have emerged as highly effective antiviral agents [146] . A number of nucleoside and non‐nucleoside pyridine analogs 75 a – j (Figure 20) were reported and analyzed by Ibrahim et al .…”

Recent Advances in the Design and Development of Non‐nucleoside Reverse Transcriptase Inhibitor Scaffolds

“…Further modificationso ft he lead compound MC-1220 resulted in the identification of 79 and 80 with high potency against the wild-type HIV-1 strain (Figure 38). [50] Good activity profile and high selectivity indices are the essentialf actors for an anti-HIV-1 agent to be used as at opical microbicide. Therefore, to obtain ap otent NNRTI formulated as am icrobicide gel, an ew series of N-DABOs were synthesized.…”

“…Further modifications of the lead compound MC‐1220 resulted in the identification of 79 and 80 with high potency against the wild‐type HIV‐1 strain (Figure ) …”

Synthesis, Characterization and Docking Study of Novel Pyrimidine Derivatives as Anticancer Agents

“…Gene-therapy in recent research was based on DNA and its modification [8][9][10]. The thymidine ring is a DNA building block that interests many researchers to focused their research on the synthesis of new pyrimidine rings as anti-cancer agents such as 5-fluorouracil [1][2][3][4][5][6][7][8][9][10][11][12][13][14], and anti-HIV like AZT, D4T, Nikavir [15][16][17][18][19][20][21], Lamivudina [22] and Emtricitabina [16,[23][24]. The Nitrogen containing heterocycles like pyrimidines and their derivatives have received great attention for their considerable exciting biological activities [25][26][27][28].…”