Synthetic Route of C6H12N2OOn May 8, 2020 ,《Identifying Oxacillinase-48 Carbapenemase Inhibitors Using DNA-Encoded Chemical Libraries》 appeared in ACS Infectious Diseases. The author of the article were Taylor, Doris Mia; Anglin, Justin; Park, Suhyeorn; Ucisik, Melek N.; Faver, John C.; Simmons, Nicholas; Jin, Zhuang; Palaniappan, Murugesan; Nyshadham, Pranavanand; Li, Feng; Campbell, James; Hu, Liya; Sankaran, Banumathi; Prasad, B. V. Venkataram; Huang, Hongbing; Matzuk, Martin M.; Palzkill, Timothy. The article conveys some information:
Bacterial resistance to β-lactam antibiotics is largely mediated by β-lactamases, which catalyze the hydrolysis of these drugs and continue to emerge in response to antibiotic use. β-Lactamases that hydrolyze the last resort carbapenem class of β-lactam antibiotics (carbapenemases) are a growing global health threat. Inhibitors have been developed to prevent β-lactamase-mediated hydrolysis and restore the efficacy of these antibiotics. However, there are few inhibitors available for problematic carbapenemases such as oxacillinase-48 (OXA-48). A DNA-encoded chem. library approach was used to rapidly screen for compounds that bind and potentially inhibit OXA-48. Using this approach, a hit compound, CDD-97(), was identified with submicromolar potency (Ki = 0.53 ± 0.08μM) against OXA-48. X-ray crystallog. showed that CDD-97 binds noncovalently in the active site of OXA-48. Synthesis and testing of derivatives of CDD-97 revealed structure-activity relationships and informed the design of a compound with a 2-fold increase in potency. CDD-97, however, synergizes poorly with β-lactam antibiotics to inhibit the growth of bacteria expressing OXA-48 due to poor accumulation into E. coli. Despite the low in vivo activity, CDD-97 provides new insights into OXA-48 inhibition and demonstrates the potential of using DNA-encoded chem. technol. to rapidly identify β-lactamase binders and to study β-lactamase inhibition, leading to clin. useful inhibitors. In the part of experimental materials, we found many familiar compounds, such as Piperidine-4-carboxamide(cas: 39546-32-2Synthetic Route of C6H12N2O)
Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.Synthetic Route of C6H12N2O
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem