14597-58-1Relevant articles and documents
Discovery of a novel series of guanidinebenzoates as gut-restricted enteropeptidase and trypsin dual inhibitors for the treatment of metabolic syndrome
Zhang, Xuqing,Zhu, Bin,Sun, Weimei,Wang, Mina,Albarazanji, Kamal,Ghosh, Brahma,Cummings, Maxwell,Lenhard, James,Leonard, James,Macielag, Mark,Lanter, James
, (2021)
A novel series of guanidinebenzoate enteropeptidase and trypsin dual inhibitors has been discovered and SAR studies were conducted. Optimization was focused on improving properties for gut restriction, including increased aqueous solubility, lower cellular permeability, and reduced oral bioavailability. Lead compounds were identified with efficacy in a mouse fecal protein excretion study.
Design, synthesis, and biological evaluation of 2-(phenoxyaryl)-3-urea derivatives as novel P2Y1 receptor antagonists
Peng, Jingjing,Zhao, Lifen,Wang, Lanlan,Chen, Hui,Qiu, Yunguang,Wang, Jiang,Yang, Huaiyu,Liu, Jun,Liu, Hong
, p. 302 - 310 (2018/09/18)
A novel series of 2-(phenoxyaryl)-3-urea derivatives were designed, synthesized, and biologically evaluated for their anti-thrombotic activity. Most of compounds exhibited good inhibition against P2Y1 receptor. Among them, three compounds 11, 12, and 13 demonstrated good P2Y1 receptor antagonistic potency in vitro (IC50 = 0.62 μM, 0.82 μM, and 0.21 μM, respectively). In antiplatelet aggregation study, four compounds 2, 3, 9, and 13 showed good antiplatelet activity. The possible binding modes of compounds with P2Y1 receptor were also explored by molecular docking simulation. The docking studies demonstrated that compound 13 interacted well with Phe119 through hydrophobic interaction and modestly improved the P2Y1 receptor antagonistic activity, making it justifiable for further investigation.
Optimization of potent inhibitors of P. falciparum dihydroorotate dehydrogenase for the treatment of malaria
Skerlj, Renato T.,Bastos, Cecilia M.,Booker, Michael L.,Kramer, Martin L.,Barker, Robert H.,Celatka, Cassandra A.,O'Shea, Thomas J.,Munoz, Benito,Sidhu, Amar Bir,Cortese, Joseph F.,Wittlin, Sergio,Papastogiannidis, Petros,Angulo-Barturen, Inigo,Jimenez-Diaz, Maria Belen,Sybertz, Edmund
supporting information; experimental part, p. 708 - 713 (2011/11/04)
Inhibition of dihydroorotate dehydrogenase (DHODH) for P. falciparum potentially represents a new treatment option for malaria, since DHODH catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and P. falciparum is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. We report herein the synthesis and structure-activity relationship of a series of 5-(2-methylbenzimidazol-1-yl)-N-alkylthiophene-2-carboxamides that are potent inhibitors against PfDHODH but do not inhibit the human enzyme. On the basis of efficacy observed in three mouse models of malaria, acceptable safety pharmacology risk assessment and safety toxicology profile in rodents, lack of potential drug-drug interactions, acceptable ADME/pharmacokinetic profile, and projected human dose, 5-(4-cyano-2-methyl-1H-benzo[d]imidazol-1-yl) -N-cyclopropylthiophene-2-carboxamide 2q was identified as a potential drug development candidate.
