1282449-08-4

Upstream product

• 1062292-98-1 ethyl 5-cyano-1-(4-hydroxyphenyl)-4-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylate 
• 1062292-56-1 ethyl 5-amino-3-(4-hydroxyphenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 
• 123-30-8 4-amino-phenol 
• 132577-23-2 ethyl 2,3-dioxobutanoate 2-(4-hydroxyphenyl)hydrazone 

Downstream Products

• 1282449-15-3 5-amino-3-(4-hydroxyphenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide 

Relevant academic research and scientific papers

HETEROCYCLIC COMPOUNDS AS IMAGING PROBES OF TAU PATHOLOGY

Pyridazinone compounds of Formula I: (I) wherein: R' is alkyl or Ar, optionally substituted with at least one alkyl, halo? gen, hydroxyl, alkoxy, haloalkoxy, acid, ester, amino, nitro, amide, or alkoxyhalo; 2 R is independently alkyi, alkynyl, ester, amino, amide, acid, aryl, heteroaryl, aminoalkyl, -C(=0)alkyl, -C(=0)aryl, -C(=0)heteroaryl, -C(=0)heterocycloalkyl, - C(=0)heterocycloalkylAr, -C(=0)(CH2)nhalo, -C(=0)(CH2)nheterocyclyl, or -SC^Ar, optionally substituted with at least one alkyi, alkylhalo, halogen, nitro, aryl, heteroaryl, or heteroaryl(CH2)nhalo; R 3 and R4 are independently hydrogen, alkyi, alkenyl, alkynyl, aryl, heteroaryl; Ar is an aryl, heteroaryl, cycloalkyl, heterocycloalkyl group; n is an integer from 0-10; or a radiolabeled derivative thereof. The compounds are useful as imaging probes of Tau pathology in Alzheimer's disease are described. Compositions and methods of making such compounds are also described.

Aminothienopyridazine inhibitors of tau aggregation: Evaluation of structure-activity relationship leads to selection of candidates with desirable in vivo properties

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.

AMINOTHIENOPYRIDAZINE INHIBITORS OF TAU ASSEMBLY

The present invention is directed to methods of inhibiting a tauopathy in a patient by administration of a compound of formula (I): Novel aminothienopyridazine compounds are also described.