Discovery of Novel Substituted N-(4-Amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide Analogues as Potent Human Adenovirus Inhibitors was written by Xu, Jimin;Berastegui-Cabrera, Judith;Ye, Na;Carretero-Ledesma, Marta;Pachon-Diaz, Jeronimo;Chen, Haiying;Pachon-Ibanez, Maria Eugenia;Sanchez-Cespedes, Javier;Zhou, Jia. And the article was included in Journal of Medicinal Chemistry in 2020.Safety of 5-Chloro-2-methoxybenzoic acid This article mentions the following:
An effective therapy for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-acquired pneumonia remains an unmet medical need. Herein the synthesis and evaluation of a series of novel substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogs, e.g., I (R1 = H, R2 = H, MeCO, Et, cyclopentyl, PhCH2, 4-pyridylmethyl, etc.; R1 = R2 = Me, Et, N-Pr, cyclopropylmethyl; etc.), as potent HAdV inhibitors are reported. Compounds I (R1 = H; R2 = cyclopentyl, 1-methylcyclopentyl, 4-HOC6H4CH2, 2-hydroxy-5-pyridylmethyl, HOCH2CH2CMe2, HOCH2CH2CHMe, N-Boc-piperidin-4-ylmethyl) and I (R1 = PhCH2CMe2O; R2 = PhCH2CMe2) exhibited increased selectivity indexes (SI > 100) compared to the lead compound niclosamide, while maintaining sub-micromolar to low micromolar potency against HAdV. The preliminary mechanistic studies indicated that compounds I (R1 = H; R2 = cyclopentyl) and I (R1 = PhCH2CMe2O; R2 = PhCH2CMe2) possibly target the HAdV DNA replication process, while compounds I (R1 = H; R2 = HOCH2CH2CHMe, HOCH2CH2CMe2) suppress later steps of HAdV life cycle. Notably, among these derivatives, compound I (R1 = H; R2 = 1-methylcyclopentyl) showed improved anti-HAdV activity (IC50 = 0.27μM), significantly decreased cytotoxicity (CC50 = 156.8μM), and low in vivo toxicity (maximum tolerated dose = 150 mg/kg in hamster) as compared with niclosamide, supporting its further in vivo efficacy studies for the treatment of HAdV infections. In the experiment, the researchers used many compounds, for example, 5-Chloro-2-methoxybenzoic acid (cas: 3438-16-2Safety of 5-Chloro-2-methoxybenzoic acid).
5-Chloro-2-methoxybenzoic acid (cas: 3438-16-2) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Aryl chlorides may be prepared by the Friedel-Crafts halogenation, using chlorine and a Lewis acid catalyst.Safety of 5-Chloro-2-methoxybenzoic acid
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics