1062292-52-7

Upstream product

• 123534-18-9 ethyl 1-(3-chlorophenyl)-5-cyano-4-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylate 
• 108-42-9 3-chloro-aniline 
• 20954-21-6 ethyl 2,3-dioxobutanoate 2-(3-chlorophenyl)hydrazone 

Downstream Products

• 1315321-63-1 ethyl 3-(3-chlorophenyl)-5-(N-methylacetamido)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 
• 1315321-69-7 ethyl 3-(3-chlorophenyl)-5-(methylamino)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 
• 1315321-70-0 butyl 5-(butylamino)-3-(3-chlorophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 
• 1315321-72-2 ethyl 5-(benzylamino)-3-(3-chlorophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 
• 1315321-75-5 C₂₄H₂₈ClN₃O₅S 
• 1315321-74-4 C₂₆H₃₂ClN₃O₅S 
• 1315321-68-6 ethyl 5-((tert-butoxycarbonyl)amino)-3-(3-chlorophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 
• 890873-89-9 ethyl 5-acetamido-3-(3-chlorophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 
• 1315321-62-0 ethyl 3-(3-chlorophenyl)-4-oxo-5-(2,2,2-trifluoroacetamido)-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylate 
• 1282449-10-8 5-amino-3-(3-chlorophenyl)-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxylic acid 
• 1282449-13-1 5-amino-3-(3-chlorophenyl)-N-isopropyl-4-oxo-3,4-dihydrothieno[3,4-d]pyridazine-1-carboxamide 

Relevant academic research and scientific papers

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.

2-Aminothienopyridazines as novel adenosine A1 receptor allosteric modulators and antagonists

A pharmacophore-based screen identified 32 compounds including ethyl 5-amino-3-(4-tert-butylphenyl)-4-oxo-3,4-dihydrothieno[3,4-d] pyridazine-1-carboxylate (8) as a new allosteric modulator of the adenosine A1 receptor (A1AR). On the basis of this lead, various derivatives were prepared and evaluated for activity at the human A 1AR. A number of the test compounds allosterically stabilized agonist-receptor-G protein ternary complexes in dissociation kinetic assays, but were found to be more potent as antagonists in subsequent functional assays of ERK1/2 phosphorylation. Additional experiments on the most potent antagonist, 13b, investigating A1AR-mediated [35S]GTPγS binding and [3H]CCPA equilibrium binding confirmed its antagonistic mode of action and also identified inverse agonism. This study has thus identified a new class of A1AR antagonists that can also recognize the receptor's allosteric site with lower potency.