905986-91-6Relevant articles and documents
Structure-Based Design and Synthesis of Piperidinol-Containing Molecules as New Mycobacterium abscessus Inhibitors
Biot, Christophe,Blaise, Micka?l,Dubar, Faustine,Dupont, Christian,Grassin-Delyle, Stanislas,Guérardel, Yann,Herrmann, Jean-Louis,Kremer, Laurent,Lamy, Elodie,Le Moigne, Vincent,de Ruyck, Jér?me
, p. 351 - 365 (2020/04/15)
Non-tuberculous mycobacterium (NTM) infections, such as those caused by Mycobacterium abscessus, are increasing globally. Due to their intrinsic drug resistance, M. abscessus pulmonary infections are often difficult to cure using standard chemotherapy. We previously demonstrated that a piperidinol derivative, named PIPD1, is an efficient molecule both against M. abscessus and Mycobacterium tuberculosis, the agent of tuberculosis, by targeting the mycolic acid transporter MmpL3. These results prompted us to design and synthesize a series of piperidinol derivatives and to determine the biological activity against M. abscessus. Structure-activity relationship (SAR) studies pointed toward specific sites on the scaffold that can tolerate slight modifications. Overall, these results identified FMD-88 as a new promising active analogue against M. abscessus. Also, we determined the pharmacokinetics properties of PIPD1 and showed that intraperitoneal administration of this compound resulted in promising serum concentration and an elimination half-life of 3.2 hours.
Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties
Bridges, Thomas M.,Brady, Ashley E.,Phillip Kennedy,Nathan Daniels,Miller, Nicole R.,Kim, Kwango,Breininger, Micah L.,Gentry, Patrick R.,Brogan, John T.,Jones, Carrie K.,Jeffrey Conn,Lindsley, Craig W.
experimental part, p. 5439 - 5442 (2009/06/02)
This Letter describes the first account of the synthesis and SAR, developed through an iterative analogue library approach, of analogues of the highly selective M1 allosteric agonist TBPB. With slight structural changes, mAChR selectivity was maintained, but the degree of partial M1 agonism varied considerably.
