The preparation of ester heterocycles mostly uses heteroatoms as nucleophilic sites, which are achieved by intramolecular substitution or addition reactions. Compound: Methyl 6-bromonicotinate( cas:26218-78-0 ) is researched.SDS of cas: 26218-78-0.Szalaj, Natalia; Lu, Lu; Benediktsdottir, Andrea; Zamaratski, Edouard; Cao, Sha; Olanders, Gustav; Hedgecock, Charles; Karlen, Anders; Erdelyi, Mate; Hughes, Diarmaid; Mowbray, Sherry L.; Brandt, Peter published the article 《Boronic ester-linked macrocyclic lipopeptides as serine protease inhibitors targeting Escherichia coli type I signal peptidase》 about this compound( cas:26218-78-0 ) in European Journal of Medicinal Chemistry. Keywords: macrocyclic lipopeptide boronic ester design synthesis serine protease inhibitor; drug design toxicity antibacterial structure activity mol docking conformation; solid phase peptide synthesis macrocyclization hydrolysis free energy DFT; methyl bromonicotinate Suzuki Sonogashira coupling boronic acid octyne microwave; formylation condensation iodination biphenylboronic acid coupling ethyl propiolate hydrolysis; Antibacterial lipopeptides; Bacterial type I signal peptidase; Escherichia coli type I signal peptidase (EcLepB); P2–P1′ boronic ester-linked macrocycles. Let’s learn more about this compound (cas:26218-78-0).
Type I signal peptidase, with its vital role in bacterial viability, is a promising but underexploited antibacterial drug target. In the light of steadily increasing rates of antimicrobial resistance, we have developed novel macrocyclic lipopeptides, linking P2 and P1′ by a boronic ester warhead, capable of inhibiting Escherichia coli type I signal peptidase (EcLepB) and exhibiting good antibacterial activity. Structural modifications of the macrocyclic ring, the peptide sequence and the lipophilic tail led us to 14 novel macrocyclic boronic esters. It could be shown that macrocyclization is well tolerated in terms of EcLepB inhibition and antibacterial activity. Among the synthesized macrocycles, potent enzyme inhibitors in the low nanomolar range (e.g. EcLepB IC50 = 29 nM) were identified also showing good antimicrobial activity (e.g. E. coli WT MIC = 16 μg/mL). The unique macrocyclic boronic esters described here were based on previously published linear lipopeptidic EcLepB inhibitors in an attempt to address cytotoxicity and hemolysis. We show herein that structural changes to the macrocyclic ring influence both the cytotoxicity and hemolytic activity suggesting that the P2 to P1′ linker provide means for optimizing off-target effects. However, for the present set of compounds we were not able to sep. the antibacterial activity and cytotoxic effect.
Here is just a brief introduction to this compound(26218-78-0)SDS of cas: 26218-78-0, more information about the compound(Methyl 6-bromonicotinate) is in the article, you can click the link below.
Reference:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem