CAY10742 is an orally bioavailable oxadiazole antibiotic.1It is active against the Gram-positive bacteriaS. aureus,S. epidermidis,S. haemolyticus,B. cereus,B. licheniformis,E. faecalis, andE. faecium(MICs = 1-4 μg/ml), including laboratory strains and clinical isolates with varying degrees of resistance to methicillin, vancomycin, linezolid, and other antibiotics. CAY10742 (40 mg/kg) reduces the number of bacteria in mouse neutropenic thigh models of linezolid-sensitive or -resistant methicillin-resistantS. aureus(MRSA) infection.
1.Boudreau, M.A., Ding, D., Meisel, J.E., et al.Structure-activity relationship for the oxadiazole class of antibacterialsMed. Chem. Lett.11(3)322-326(2019)
CAY10761 is an inhibitor of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; IC50s = 467 and 429 μM for the human and snake venom enzymes, respectively).1,2 It also inhibits mushroom tyrosinase (Ki = 1.9 μM) and urease from jack bean, P. mirabilis, and B. pasteurii (IC50s = 0.093, <0.125, and 0.089 mM, respectively, at pH 8.2).3,4
|1. Khan, K.M., Fatima, N., Rasheed, M., et al. 1,3,4-Oxadiazole-2(3H)-thione and its analogues: A new class of non-competitive nucleotide pyrophosphatases/phosphodiesterases 1 inhibitors. Bioorg. Med. Chem. 17(22), 7816-7822 (2009).|2. Onyedibe, K.I., Wang, M., and Sintim, H.O. ENPP1, an old enzyme with new functions, and small molecule inhibitors - A STING in the tale of ENPP1. Molecules 24(22), E4192 (2019).|3. Ghani, U., and Ullah, N. New potent inhibitors of tyrosinase: Novel clues to binding of 1,3,4-thiadiazole-2(3H)-thiones, 1,3,4-oxadiazole-2(3H)-thiones, 4-amino-1,2,4-triazole-5(4H)-thiones, and substituted hydrazides to the dicopper active site. Bioorg. Med. Chem. 18(11), 4042-4048 (2010).|4. Amtul, Z., Rasheed, M., Choudhary, M.I., et al. Kinetics of novel competitive inhibitors of urease enzymes by a focused library of oxadiazoles/thiadiazoles and triazoles. Biochem. Biophys. Res. Commun. 319(3), 1053-1063 (2004).
Pifexole is the 1,2,4-oxadiazole derivative. It has a similar profile of muscle-relaxant activity in animals to that of chlorzoxazone. In rats, pifexole is reported to be seven times more potent than chlorzoxazone in inhibition of strychnine-induced convulsions.