156484-83-2Relevant academic research and scientific papers
Discovery, Structure-Activity Relationship, and Binding Mode of an Imidazo[1,2-a]pyridine Series of Autotaxin Inhibitors
Joncour, Agnès,Desroy, Nicolas,Housseman, Christopher,Bock, Xavier,Bienvenu, Natacha,Cherel, La?titia,Labeguere, Virginie,Peixoto, Christophe,Annoot, Denis,Lepissier, Luce,Heiermann, J?rg,Hengeveld, Willem Jan,Pilzak, Gregor,Monjardet, Alain,Wakselman, Emanuelle,Roncoroni, Veronique,Le Tallec, Sandrine,Galien, René,David, Christelle,Vandervoort, Nele,Christophe, Thierry,Conrath, Katja,Jans, Mia,Wohlkonig, Alexandre,Soror, Sameh,Steyaert, Jan,Touitou, Robert,Fleury, Damien,Vercheval, Lionel,Mollat, Patrick,Triballeau, Nicolas,Van Der Aar, Ellen,Brys, Reginald,Heckmann, Bertrand
, p. 7371 - 7392 (2017/09/23)
Autotaxin (ATX) is a secreted enzyme playing a major role in the production of lysophosphatidic acid (LPA) in blood through hydrolysis of lysophosphatidyl choline (LPC). The ATX-LPA signaling axis arouses a high interest in the drug discovery industry as it has been implicated in several diseases including cancer, fibrotic diseases, and inflammation, among others. An imidazo[1,2-a]pyridine series of ATX inhibitors was identified out of a high-throughput screening (HTS). A cocrystal structure with one of these compounds and ATX revealed a novel binding mode with occupancy of the hydrophobic pocket and channel of ATX but no interaction with zinc ions of the catalytic site. Exploration of the structure-activity relationship led to compounds displaying high activity in biochemical and plasma assays, exemplified by compound 40. Compound 40 was also able to decrease the plasma LPA levels upon oral administration to rats.
Synthesis and bioactivity of substituted indan-1-ylideneaminoguanidine derivatives
Zhang, Rui,Dong, Jin,Xu, Yun-gen,Hua, Wei-yi,Wen, Na,You, Qi-dong
experimental part, p. 3771 - 3776 (2009/12/04)
In our efforts to discover more potent and lasting NHE1 inhibitors, we designed and synthesized a series of substituted indan-1-ylidene aminoguanidine derivatives (5). NHE1 inhibitory activity of twenty-one compounds 5 was evaluated in a rat platelet swelling assay. It is found that most of the tested compounds possess NHE1 inhibitory effects. 2-(5-methoxybenzimidazol-2-ylthio)-5-chloro-2,3-dihydroinden-1-ylidene aminoguanidine hydrobromide (5m) proved to be sixty-nine times more potent than cariporide. Furthermore, when tested in vivo, compound 5m also displayed superior cardioprotective effects against SD rat myocardial ischemic-reperfusion injury over those of cariporide.
Improvement in the selectivity and metabolic stability of the serotonin 5-HT1A ligand, S 15535: A series of cis- and trans-2-(arylcycloalkylamine) 1-indanols
Peglion,Goument,Despaux,Charlot,Giraud,Nisole,Newman-Tancredi,Dekeyne,Bertrand,Genissel,Millan
, p. 165 - 176 (2007/10/03)
S 15535 (1) displays a distinctive profile of agonist and antagonist (weak partial agonist) activity at pre- and postsynaptic 5-HT1A receptors, respectively. It has proven to be active in several models predictive of anxiolytic, antidepressant,
8-Methylureido-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]pyrazines : Highly potent in vivo AMPA antagonists
Mignani, Serge,Bohme, Georg Andrees,Boireau, Alain,Cheve, Michel,Damour, Dominique,Debono, Marc-Williams,Genevois-Borella, Arielle,Imperato, Assunta,Jimonet, Patrick,Pratt, Jeremy,Randle, John C.R.,Ribeill, Yves,Vuilhorgne, Marc,Stutzmann, Jean-Marie
, p. 591 - 596 (2007/10/03)
A novel series of readily water soluble 8-methylureido-4,5-dihydro-4-oxo-10H-imidazo[1,2-a]indeno[1,2-e]pyrazines were synthesized. The -10-yl acetic acid ((+)-3) and -10-carboxylidene (4) derivatives exhibit potent affinities (IC50 = 4 and 19 nM, respectively) and antagonist properties (IC50 = 2 and 3 nM, respectively) at the ionotropic AMPA receptor. These compounds also display anticonvulsant properties against both electrically and sound-induced convulsions in mice after ip, sc and iv administration with ED50 values between 0.9 and 11 mg/kg, thus suggesting adequate brain penetration. (C) 2000 Elsevier Science Ltd. All rights reserved.
