Abstract This report explores the potential of novel 6‐aryloxy‐2‐aminopyrimidine‐benzonitrile scaffolds as promising anti‐infective agents in the face of the increasing threat of infectious diseases. Starting from 2‐amino‐4,6‐dichloropyrimidine, a series of 24 compounds inspired from the antiviral drugs dapivirine, etravirine, and rilpivirine were designed and synthesized via a two‐step reaction sequence in good yields. Biological testing of synthetic analogs revealed potent inhibition against both viral and tuberculosis targets. Notably, compounds 5p (2,4‐dimethyl substitution; IC 50 = 44 ± 4.9 µM; selectivity index [SI] = 20) and 5 s (3‐thiophenphenyl; IC 50 = 6 ± 1 µM; SI = 120) showed significant antiviral activity against pandemic influenza virus A/Puerto Rico/8/34 (H1N1) with positive toxicity profiles and also exhibited good IC 50 values ( 5p , IC 50 = 10 ± 2 µM; SI = 9 and 5 s , IC 50 = 16 ± 2 µM; SI = 60) against the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) (Wuhan strain) compared with favipiravir. In addition, analogs 5a , 5r , 5t , and 5u showed good antitubercular activity against Mycobacterium tuberculosis H37Rv strain and compounds 3 , 5f , 5n , and 5q showed moderate antibacterial activity against gram+ve and gram‐ve bacterial strains, suggesting that this scaffold has a broad spectrum of therapeutic effects.

Abburi Naga Pranathi

Nagineni Devendra

Rakesh K. Bollikanda

Pavan K. Bangalore

Iana L. Esaulkova

Mikhail G. Mikhalsky

Maria A. Niukalova

Vladimir V. Zarubaev

Balasubramanian Sridhar

Srinivas Kantevari

Archiv der Pharmazie

ARCHIV DER PHARMAZIE - CHEMISTRY IN LIFE SCIENCES 是一份致力于药物和药物化学各个领域研究和开发的国际期刊。重点放在将合成有机化学、结构生物学、分子建模、生物有机化学、天然产物化学、生物化学或分析方法与生物活性等药物或医学方面相结合的论文。该期刊的重点是原创研究论文，但也欢迎其他具有科学价值的贡献（例如评论、小型评论、亮点、专题讨论会贡献、讨论和论文）。

ARCHIV DER PHARMAZIE - CHEMISTRY IN LIFE SCIENCES is an international journal dedicated to research and development in all areas of pharmaceuticals and pharmaceutical chemistry. The focus is on papers that integrate synthetic organic chemistry, structural biology, molecular modeling, bioorganic chemistry, natural product chemistry, biochemistry, or analytical methods with bioactivity related to drugs or medicine. The journal primarily publishes original research articles but also welcomes other scientifically valuable contributions, such as reviews, mini-reviews, highlights, contributions to special discussions, discussions, and papers.

《ARCHIV DER PHARMAZIE - CHEMISTRY IN LIFE SCIENCES》是一份国际期刊，专注于药物和药物化学的各个研究领域。期刊的重点在于将合成有机化学、结构生物学、分子建模、生物有机化学、天然产物化学、生物化学及分析方法与药物或医学相关的生物活性相结合。该期刊主要发表原创研究论文，同时也欢迎其他具有科学价值的贡献，如评论、小型评论、亮点、专题讨论会贡献、讨论和论文。

Category	Quartile
医学	3
医学, 化学综合	2
医学, 药学	2
医学, 药物化学	3

6‐aryloxy‐2‐aminopyrimidine‐benzonitrile hybrids as anti‐infective agents: Synthesis, bioevaluation, and molecular docking

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Category	Quartile
PHARMACOLOGY & PHARMACY	1