1261118-06-2Relevant academic research and scientific papers
An efficient, stereocontrolled and versatile synthetic route to bicyclic partially saturated privileged scaffolds
Bond, Andrew D.,Hanby, Abigail R.,King, Thomas A.,Moss, Thomas A.,Sore, Hannah F.,Spring, David R.,Stewart, Hannah L.
, p. 6818 - 6821 (2020/07/04)
Herein, we describe the development of a simple, high yielding and stereocontrolled strategy for the synthesis of a series of triazolopiperazines and other biologically relevant fused scaffolds from optically active amino acids. This route was applied to the synthesis of 22 scaffolds containing new, previously inaccessible vectors and used to access a novel analogue of ganaplacide.
Imidazolopiperazines: Lead optimization of the second-generation antimalarial agents
Nagle, Advait,Wu, Tao,Kuhen, Kelli,Gagaring, Kerstin,Borboa, Rachel,Francek, Caroline,Chen, Zhong,Plouffe, David,Lin, Xuena,Caldwell, Christopher,Ek, Jared,Skolnik, Suzanne,Liu, Fenghua,Wang, Jianling,Chang, Jonathan,Li, Chun,Liu, Bo,Hollenbeck, Thomas,Tuntland, Tove,Isbell, John,Chuan, Tiffany,Alper, Philip B.,Fischli, Christoph,Brun, Reto,Lakshminarayana, Suresh B.,Rottmann, Matthias,Diagana, Thierry T.,Winzeler, Elizabeth A.,Glynne, Richard,Tully, David C.,Chatterjee, Arnab K.
, p. 4244 - 4273 (2012/07/03)
On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the compounds by leveraging the outcome of a set of in vitro metabolic identification studies. The optimized 8,8-dimethyl imidazolopiperazine analogues exhibited improved potency, in vitro metabolic stability profile and, as a result, enhanced oral exposure in vivo in mice. The optimized compounds were found to be more efficacious than the current antimalarials in a malaria mouse model. They exhibit moderate oral exposure in rat pharmacokinetic studies to achieve sufficient multiples of the oral exposure at the efficacious dose in toxicology studies.
