123534-18-9Relevant articles and documents
Aminothienopyridazine inhibitors of tau aggregation: Evaluation of structure-activity relationship leads to selection of candidates with desirable in vivo properties
Ballatore, Carlo,Crowe, Alex,Piscitelli, Francesco,James, Michael,Lou, Kevin,Rossidivito, Gabrielle,Yao, Yuemang,Trojanowski, John Q.,Lee, Virginia M.-Y.,Brunden, Kurt R.,Smith III, Amos B.
experimental part, p. 4451 - 4461 (2012/08/28)
Previous studies demonstrated that members of the aminothienopyridazine (ATPZ) class of tau aggregation inhibitors exhibit a promising combination of in vitro activity as well as favorable pharmacokinetic properties (i.e., brain-penetration and oral bioavailability). Here we report the synthesis and evaluation of several new analogues. These studies indicate that the thienopyridazine core is essential for inhibition of tau fibrillization in vitro, while the choice of the appropriate scaffold decoration is critical to impart desirable ADME-PK properties. Among the active, brain-penetrant ATPZ inhibitors evaluated, 5-amino-N-cyclopropyl-3-(4-fluorophenyl)-4-oxo-3,4- dihydrothieno[3,4-d]pyridazine-1-carboxamide (43) was selected to undergo maximum tolerated dose and one-month tolerability testing in mice. The latter studies revealed that this compound is well-tolerated with no notable side-effects at an oral dose of 50 mg/kg/day.
Studies on Alkyl Heterocyclic Aromatic Compounds: New Routes for the Synthesis of Polyazanaphthalenes
Elnagdi, Mohamed Hilmy,Aal, Fatma Abdel Maksoud Abdel,Hafez, Ebtisam Abdel Aziz,Yassin, Youssef Mahfouz
, p. 683 - 689 (2007/10/02)
Several new polyfunctionally substituted polyazanaphthalene derivatives could be synthesized via condensing readily obtainable polyfunctional nitriles with substituted akyl heteroaromatic derivatives and reacting the latter derivatives with electrophilic
