860004-31-5Relevant articles and documents
Structure-Activity Relationship Studies of Tolfenpyrad Reveal Subnanomolar Inhibitors of Haemonchus contortus Development
Le, Thuy G.,Kundu, Abhijit,Ghoshal, Atanu,Nguyen, Nghi H.,Preston, Sarah,Jiao, Yaqing,Ruan, Banfeng,Xue, Lian,Huang, Fei,Keiser, Jennifer,Hofmann, Andreas,Chang, Bill C. H.,Garcia-Bustos, Jose,Wells, Timothy N. C.,Palmer, Michael J.,Jabbar, Abdul,Gasser, Robin B.,Baell, Jonathan B.
, p. 1036 - 1053 (2019/01/14)
Recently, we have discovered that the registered pesticide, tolfenpyrad, unexpectedly and potently inhibits the development of the L4 larval stage of the parasitic nematode Haemonchus contortus with an IC50 value of 0.03 μM while displaying good selectivity, with an IC50 of 37.9 μM for cytotoxicity. As a promising molecular template for medicinal chemistry optimization, we undertook anthelmintic structure-activity relationships for this chemical. Modifications of the left-hand side (LHS), right-hand side (RHS), and middle section of the scaffold were explored to produce a set of 57 analogues. Analogues 25, 29, and 33 were shown to be the most potent compounds of the series, with IC50 values at a subnanomolar level of potency against the chemotherapeutically relevant fourth larval (L4) stage of H. contortus. Selected compounds from the series also showed promising activity against a panel of other different parasitic nematodes, such as hookworms and whipworms.
Copper mediated formation of carbon-heteroatom bonds using organoboron reagents and ultrasound
Musolino, Bryan J.,Kabalka, George W.
, p. 271 - 297 (2015/03/04)
This report summarizes research efforts focused on copper acetate mediated reactions to form new carbon-heteroatom bonds using organoboron reagents under ultrasound irradiation. The method involves the application of ultrasound irradiation to the Chan-Evans-Lam reaction to achieve O-arylation of phenols, N-arylation of anilines and indoles, and S-arylation of thiols. Ultrasound irradiation was found to decrease reaction times from 72 hours to 4 hours while improving the product yields an average of 20%.1 Representative C-O, C-N, and C-S coupling reactions were successfully scaled-up from the milligram to gram levels while maintaining good product yields offering potential applications in industrial processes.
Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity
O'Daniel, Peter I.,Peng, Zhihong,Pi, Hualiang,Testero, Sebastian A.,Ding, Derong,Spink, Edward,Leemans, Erika,Boudreau, Marc A.,Yamaguchi, Takao,Schroeder, Valerie A.,Wolter, William R.,Llarrull, Leticia I.,Song, Wei,Lastochkin, Elena,Kumarasiri, Malika,Antunes, Nuno T.,Espahbodi, Mana,Lichtenwalter, Katerina,Suckow, Mark A.,Vakulenko, Sergei,Mobashery, Shahriar,Chang, Mayland
, p. 3664 - 3672 (2014/03/21)
Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.
