《Design, synthesis and biological activity of novel substituted 3-benzoic acid derivatives as MtDHFR inhibitors》 was published in Bioorganic & Medicinal Chemistry in 2020. These research results belong to Kronenberger, Thales; Ferreira, Glaucio Monteiro; Ferreira de Souza, Alfredo Danilo; da Silva Santos, Soraya; Poso, Antti; Ribeiro, Joao Augusto; Tavares, Mauricio Temotheo; Pavan, Fernando Rogerio; Trossini, Gustavo Henrique Goulart; Dias, Marcio Vinicius Bertacine; Parise-Filho, Roberto. Synthetic Route of C9H9BrO2 The article mentions the following:
The fragment MB872 I [R1 = H; R2 = 3-C(O)OH; W = O; Y = CH2] was used as a prototype for analog development by bioisosterism/retro-bioisosterism, which resulted in substituted 3-benzoic acid derivatives I [R1 = H, OH, OMe, NO2; R2 = 3-C(O)OH, 4-C(O)OH, 3-C(O)OMe, 4-C(O)OMe, 3-NO2; W = O, S, NH, CH2; Y = O, CH2]. Compounds I were active against MtDHFR, with IC50 values ranging from 7 to 40μM, where compound I [R1 = H; R2 = 3-C(O)OH; W = NH; Y = CH2] not only had the best inhibitory activity (IC50 = 7μM), but also was 71-fold more active than the original fragment MB872. The compound I [R1 = H; R2 = 3-C(O)OH; W = NH; Y = CH2] inhibition kinetics indicated an uncompetitive mechanism, which was supported by mol. modeling which suggested that the compounds I could access an independent backpocket from the substrate and competitive inhibitors. Thus, based on these results, substituted 3-benzoic acid derivatives I had strong potential to be developed as novel MtDHFR inhibitors and also anti-TB agents. In the experiment, the researchers used Methyl 3-(bromomethyl)benzoate(cas: 1129-28-8Synthetic Route of C9H9BrO2)
Methyl 3-(bromomethyl)benzoate(cas: 1129-28-8) belongs to organobromine compounds.The reactivity of organobromine compounds resembles but is intermediate between the reactivity of organochlorine and organoiodine compounds. Synthetic Route of C9H9BrO2 Dehydrobromination, Grignard reactions, reductive coupling, Wittig reaction, and several nucleophilic substitution reactions are some of the principal reactions which involve organic bromides.
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary