Ladduwahetty, Tammy; Lee, Matthew R.; Maillard, Michel C.; Cachope, Roger; Todd, Daniel; Barnes, Michael; Beaumont, Vahri; Chauhan, Alka; Gallati, Caroline; Haughan, Alan F.; Kempf, Georg; Luckhurst, Christopher A.; Matthews, Kim; McAllister, George; Mitchell, Philip; Patel, Hiral; Rose, Mark; Saville-Stones, Elizabeth; Steinbacher, Stefan; Stott, Andrew J.; Thatcher, Emma; Tierney, Jason; Urbonas, Liudvikas; Munoz-Sanjuan, Ignacio; Dominguez, Celia published an article in Journal of Medicinal Chemistry. The title of the article was 《Identification of a Potent, Selective, and Brain-Penetrant Rho Kinase Inhibitor and its Activity in a Mouse Model of Huntington’s Disease》.Electric Literature of C8H6N2O The author mentioned the following in the article:
The Rho kinase (ROCK) pathway is implicated in the pathogenesis of several conditions, including neurol. diseases. In Huntington’s disease (HD), ROCK is implicated in mutant huntingtin (HTT) aggregation and neurotoxicity, and members of the ROCK pathway are increased in HD mouse models and patients. To validate this mode of action as a potential treatment for HD, a potent, selective, central nervous system (CNS)-penetrant ROCK inhibitor was sought. Identifying a compound that could be dosed orally in mice with selectivity against other AGC kinases, including protein kinase G (PKG), whose inhibition could potentially activate the ROCK pathway, was paramount for the program. The optimization of published ligands to identify a novel series of ROCK inhibitors based on a piperazine core was demonstrated. Morphing of the early series developed inhouse by scaffold hopping enabled the identification of a compound exhibiting high potency and desired selectivity and demonstrating a robust pharmacodynamic (PD) effect by the inhibition of ROCK-mediated substrate (MYPT1) phosphorylation after oral dosing. The results came from multiple reactions, including the reaction of Imidazo[1,2-a]pyridine-5-carbaldehyde(cas: 372147-50-7Electric Literature of C8H6N2O)
Imidazo[1,2-a]pyridine-5-carbaldehyde(cas: 372147-50-7) belongs to imidazoles.Imidazole rings are part of unnatural cyclic peptides and are used as ester isosteres in peptidomimetic studies.
Electric Literature of C8H6N2O However, the application of imidazoles is not limited to the field of peptides and peptidomimetics.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem