60889-22-7

Upstream product

• 64223-66-1 6-methoxy-4-oxo-3,4-dihydro-phthalazine-1-carboxylic acid 
• 40125-47-1 3-Bromo-6-methoxy-3H-isobenzofuran-1-one 
• 586-38-9 3-Methoxybenzoic acid 
• 4741-63-3 6-methoxyphthalide 
• 4785-56-2 2-formyl-5-methoxy-benzoic acid 

Downstream Products

• 102196-78-1 1-chloro-7-methoxyphthalazine 

Relevant academic research and scientific papers

Quinazoline and phthalazine derivatives as novel melatonin receptor ligands analogues of agomelatine

For further development of successors of Agomelatine through modulation of its pharmacokinetic properties, we report herein the design, synthesis and pharmacological results of a new family of melatonin receptor ligands. Issued from the introduction of quinazoline and phthalazine scaffolds carrying an ethyl amide lateral chain and a methoxy group as bioisosteric ligands analogues of previously developed Agomelatine. The biological activity of the prepared analogues was compared with that of Agomelatine. Quinazoline and phthalazine rings proved to be a versatile scaffold for easy feasible MT1 and MT2 ligands. Potent agonists with sub-micromolar binding affinity were obtained. However, the presence of two nitrogen atoms resulted in compounds with lower affinity for both MT1 and MT2, in comparison with the parent compound, balanced by the exhibition of good pharmacokinetic properties.

Synthesis, biological evaluation and molecular modeling studies of phthalazin-1(2: H)-one derivatives as novel cholinesterase inhibitors

A new series of donepezil analogues based on the phthalazin-1(2H)-one scaffold was designed and synthesized with the aim of exploring its potential as human ChEIs. Biological results revealed that the structural modifications proposed significantly affected ChE inhibitory potency as well as selectivity for AChE/BuChE. Compound 1d showed promising in vitro inhibition of both enzymes in the μM range. However, most target compounds were significantly more active against AChE than BuChE, specifically 1f, 1h and 1j, with IC50 values in the low micromolar or submicromolar range, the most active compounds in the series. Docking simulations suggested that the most active compounds can recognize the donepezil binding site using a similar interactions network. These results allowed us to rationalize the observed structure-activity relationships. Moreover, the predicted physicochemical and ADME properties were also comparable to those of donepezil.

Regioselective Synthesis of Substituted 4-Alkylamino and 4-Arylaminophthalazin-1(2 H)-ones

(Chemical Equation Presented). An efficient regioselective synthesis of substituted 4-alkylamino and 4-arylaminophthalazin-1(1H)-ones 5 is described. This new method features the formation of substituted phthalazin-1(1H)-ones 3 by the reaction of 2-formylbenzoic acids 1 or 3-hydroxyisobenzofuran-1(3H)-ones 2 with hydrazine to generate phthalazin-1(2H)-ones 3. Subsequent regioselective bromination of phthalazin-1(2H)-ones 3 with benzyltrimethylammonium tribromide (BTMA-Br3) followed by mixed copper-copper oxide-catalyzed amination of 4-bromophthalazin-1(2H)-ones 4 with primary amines generates aminophthalazin-1(2H)-ones in good overall yields.

(3-ALKYLAMINO-2-HYDROXYPROPOXY)-1-HYDRAZINOPHTHALAZINES

The compounds are substituted hydrazinophthalazines which are active as β-adrenergic blocking agents and as vasodilators. A specific compound of the invention is 5-(3-t-butylamino-2-hydroxypropoxy)-1-hydrazinophthalazine.