The author of 《Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing》 were Zhao, Tong; Meng, Qing; Kang, Dongwei; Ji, Jianbo; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng. And the article was published in European Journal of Medicinal Chemistry in 2019. Safety of 2-Bromoacetamide The author mentioned the following in the article:
For more in-depth exploration of the chem. space around the entrance channel of HIV-1 reverse transcriptase (RT), a series of novel indolylarylsulfones (IASs) bearing different chiral N-substituted pyrrolidines (R/S)-I [R1 = methanesulfonyl, pyridin-3-ylmethyl, (2-fluorophenyl)methyl, (4-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl, etc.], azetidines II or substituted sulfonamide groups III [R2 = 2-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)ethyl, ethanesulfonyl, cyclopropanesulfonyl, etc.] at indole-2-carboxamide were designed and synthesized as potent HIV NNRTIs by structure-guided scaffold morphing approach. All the IASs exhibited moderate to excellent potency against wild-type HIV-1 with EC50values ranging from 0.0043 μM to 4.42 μM. Notably, compound (R)-I (R1 = methanesulfonyl) (EC50 = 4.7 nM, SI = 5183) and (S)-I (R1 = methanesulfonyl) (EC50 = 4.3 nM, SI = 7083) were identified as the most potent compounds, which were more active than nevirapine, lamivudine and efavirenz, and also reached the same order of etravirine. Furthermore, some compounds maintained excellent activity against various single HIV-1 mutants (L100I, K103 N, E138K, Y181C) as well as one double mutant (F227L/V106A) with EC50 values in low-micromolar concentration ranges. Notably, II (R2 = carbamoylmethyl) displayed outstanding potency against F227L/V106A (EC50 = 0.094 μM), and also showed exceptional activity against E138K (EC50 = 0.014 μM), L100I (EC50 = 0.011 μM) and K103 N (EC50 = 0.025 μM). Addnl., most compounds showed markedly reduced cytotoxicity (CC50) compared to lead compounds, especially II [R2 = (2-cyanophenyl)methyl] (CC50 >234.91 μM, SI >18727) and II (R2 = methanesulfonyl) (CC50 >252.49 μM, SI >15152). Preliminary SARs and mol. modeling studies were also discussed in detail, which may provide valuable insights for further optimization. In the part of experimental materials, we found many familiar compounds, such as 2-Bromoacetamide(cas: 683-57-8Safety of 2-Bromoacetamide)
2-Bromoacetamide(cas: 683-57-8) can be used in preparation of (2-carbamoylmethoxy-5-chloro-benzyl)-carbamic acid tert-butyl ester. It was aslo used as precursor to dehydropeptidase I inactivator.Safety of 2-Bromoacetamide
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics