25142-28-3Relevant articles and documents
Discovery of Imidazo[1,2-a]pyridine Ethers and Squaramides as Selective and Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthesis
Tantry, Subramanyam J.,Markad, Shankar D.,Shinde, Vikas,Bhat, Jyothi,Balakrishnan, Gayathri,Gupta, Amit K.,Ambady, Anisha,Raichurkar, Anandkumar,Kedari, Chaitanyakumar,Sharma, Sreevalli,Mudugal, Naina V.,Narayan, Ashwini,Naveen Kumar,Nanduri, Robert,Bharath, Sowmya,Reddy, Jitendar,Panduga, Vijender,Prabhakar,Kandaswamy, Karthikeyan,Saralaya, Ramanatha,Kaur, Parvinder,Dinesh, Neela,Guptha, Supreeth,Rich, Kirsty,Murray, David,Plant, Helen,Preston, Marian,Ashton, Helen,Plant, Darren,Walsh, Jarrod,Alcock, Peter,Naylor, Kathryn,Collier, Matthew,Whiteaker, James,McLaughlin, Robert E.,Mallya, Meenakshi,Panda, Manoranjan,Rudrapatna, Suresh,Ramachandran, Vasanthi,Shandil, Radha,Sambandamurthy, Vasan K.,Mdluli, Khisi,Cooper, Christopher B.,Rubin, Harvey,Yano, Takahiro,Iyer, Pravin,Narayanan, Shridhar,Kavanagh, Stefan,Mukherjee, Kakoli,Balasubramanian,Hosagrahara, Vinayak P.,Solapure, Suresh,Ravishankar, Sudha,Hameed P, Shahul
, p. 1379 - 1399 (2017/03/08)
The approval of bedaquiline to treat tuberculosis has validated adenosine triphosphate (ATP) synthase as an attractive target to kill Mycobacterium tuberculosis (Mtb). Herein, we report the discovery of two diverse lead series imidazo[1,2-a]pyridine ethers (IPE) and squaramides (SQA) as inhibitors of mycobacterial ATP synthesis. Through medicinal chemistry exploration, we established a robust structure-activity relationship of these two scaffolds, resulting in nanomolar potencies in an ATP synthesis inhibition assay. A biochemical deconvolution cascade suggested cytochrome c oxidase as the potential target of IPE class of molecules, whereas characterization of spontaneous resistant mutants of SQAs unambiguously identified ATP synthase as its molecular target. Absence of cross resistance against bedaquiline resistant mutants suggested a different binding site for SQAs on ATP synthase. Furthermore, SQAs were found to be noncytotoxic and demonstrated efficacy in a mouse model of tuberculosis infection.
One-Pot Synthesis of N-(2-Heteroaryl)-α-amino Esters by the Regiospecific 2-N-(α-Alcoxycarbonyl)alkylation of 2-Aminoazines and -azoles with Glyoxals and Alcohols Promoted by Perchloric Acid
Alcaide, Benito,Plumet, Joaquin,Sierra, Miguel A.
, p. 3143 - 3147 (2007/10/02)
2-Amino heterocycles, including pyridine, diazine, and azole derivatives, are readily converted into N-(2-heteroaryl)-α-amino esters 4 in a one-pot sequence by reaction with glyoxals and alcohols in the presence of perchloric acid.In addition, the corresp
