57835-95-7

Upstream product

• 4767-61-7 3-(4-methoxybenzylidene)phthalide 
• 71126-50-6 (3Z)-3-(4-methoxyphenylmethylidene)-2-benzofuran-1(3H)-one 
• 1190831-56-1 (Z)-N-amino-3-(4-methoxybenzylidene)isoindolin-1-one 
• 85-44-9 phthalic anhydride 
• 104-01-8 4-Methoxyphenylacetic acid 

Downstream Products

• 955359-82-7 1,1-dimethylethyl (2R)-2-{[4-(4-methoxyphenylmethyl)-1-oxo-2(1H)-phthalazinyl]methyl}pyrrolidine-1-carboxylate 
• 1622427-26-2 2-(4-(4-methoxybenzyl)-1-oxophthalazin-2(1H)-yl)-N-(4-sulfamoylphenyl)acetamide 
• 1622427-27-3 2-(4-(4-methoxybenzyl)-1-oxophthalazin-2(1H)-yl)-N-(4-(N-(pyrimidin-2-yl)sulfamoyl)phenyl)acetamide 
• 1622427-28-4 3-(4-(4-methoxybenzyl)-1-oxophthalazin-2(1H)-yl)-N-(4-sulfamoylphenyl)propanamide 
• 1622427-29-5 3-(4-(4-methoxybenzyl)-1-oxophthalazin-2(1H)-yl)-N-(4-(N-(pyrimidin-2-yl)sulfamoyl)phenyl)propanamide 

Relevant academic research and scientific papers

Increasing the binding affinity of VEGFR-2 inhibitors by extending their hydrophobic interaction with the active site: Design, synthesis and biological evaluation of 1-substituted-4-(4-methoxybenzyl)phthalazine derivatives

A series of anilinophthalazine derivatives 4a-j was initially synthesized and tested for its VEGFR-2 inhibitory activity where it showed promising activity (IC50 = 0.636-5.76 μM). Molecular docking studies guidance was used to improve the binding affinity for series 4a-j towards VEGFR-2 active site. This improvement was achieved by increasing the hydrophobic interaction with the hydrophobic back pocket of the VEGFR-2 active site lined with the hydrophobic side chains of Ile888, Leu889, Ile892, Val898, Val899, Leu1019 and Ile1044. Increasing the hydrophobic interaction was accomplished by extending the anilinophthalazine scaffold with a substituted phenyl moiety through an uriedo linker which should give this extension the flexibility required to accommodate itself deeply into the hydrophobic back pocket. As planned, the designed uriedo-anilinophthalazines 7a-i showed superior binding affinity than their anilinophthalazine parents (IC50 = 0.083-0.473 μM). In particular, compounds 7g-i showed IC50 of 0.086, 0.083 and 0.086 μM, respectively, which are better than that of the reference drug sorafenib (IC50 = 0.09 μM).

Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds

RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 μmol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella typhimurium with MIC = 0.39 and 0.78 μmol/mL, respectively.

A facile and expedient one-pot three-component reaction leading to multifunctionalized stabilized phosphorus ylides

A three-component reaction between triphenylphosphine, a dialkyl acetylenedicarboxylate and phthalazin-1(2H)-ones that affords novel organic phosphorane derivatives in good to excellent yields is reported. FTIR, 1H, 13C and 31P NMR and elemental analyses have been utilized to characterize the synthesized compounds. Indian Academy of Sciences.

The discovery of phthalazinone-based human H1 and H3 single-ligand antagonists suitable for intranasal administration for the treatment of allergic rhinitis

A series of potent phthalazinone-based human H1 and H 3 bivalent histamine receptor antagonists, suitable for intranasal administration for the potential treatment of allergic rhinitis, were identified. Blockade of H3 receptors is thought to improve efficacy on nasal congestion, a symptom of allergic rhinitis that is currently not treated by current antihistamines. Two analogues (56a and 56b) had slightly lower H1 potency (pA2 9.1 and 8.9, respectively, vs 9.7 for the clinical gold-standard azelastine, and H3 potency (pK i 9.6 and 9.5, respectively, vs 6.8 for azelastine). Compound 56a had longer duration of action than azelastine, low brain penetration, and low oral bioavailability, which coupled with the predicted low clinical dose, should limit the potential of engaging CNS-related side-effects associated with H 1 or H3 antagonism.

Tuning selectivity of anionic cyclizations: Competition between 5-exo and 6-endo-dig closures of hydrazides of o-acetylenyl benzoic acids and based-catalyzed fragmentation/recyclization of the initial 5-exo-dig products

(Chemical Equation Presented) Depending on the reaction conditions and the nature of substituents at the triple bond, anionic cyclizations of hydrazides of o-acetylenyl benzoic acids can be selectively directed along three alternative paths, each of which

2-SUBSTITUTED 4-BENZYLPHTHALAZINONE DERIVATIVES AS HISTAMINE H1 AND H3 ANTAGONISTS

The present invention relates to compounds of formula (I), and salts thereof, processes for their preparation, to compositions containing them and to their use in the treatment of various disorders, such as allergic rhinitis.

Anti-HIV activity of stilbene-related heterocyclic compounds

Viral transcription has not been routinely targeted in the development of new antiviral drugs. This crucial step of the viral cycle depends on the concerted action of cellular and viral proteins such as NF-κB and Tat. In the present study, stilbene-related heterocyclic compounds including benzalphthalide, phthalazinone, imidazoindole and pyrimidoisoindole derivatives are tested for their anti-HIV activity. Original assays based on recombinant viruses were used to evaluate HIV replication inhibition and stably transfected cell lines were used to evaluate inhibition of Tat and NF-κB proteins. Some of the stilbene-related heterocyclic compounds analysed displayed anti-HIV activity through interference with NF-κB and Tat function. Moreover, compounds inhibiting both targets displayed a stronger activity on viral replication.

Vasorelaxant activity of phthalazinones and related compounds

Several series of dihydrostilbenamide, imidazo[2,1-a]isoindole, pyrimido[2,1-a]isoindole and phthalazinone derivatives were obtained and their vasorelaxant activity was measured on isolated rat aorta rings pre-contracted with phenylephrine (10-5 M). Some phthalazinones attained, practically, the total relaxation of the organ at micromolar concentrations. For the most potent compound 9h (EC50 = 0.43 μM) the affinities for α1A, α1B and α1D adrenergic sub-receptors were determined.

The imidazo[2,1-a]isoindole system. A new skeletal basis for antiplasmodial compounds

The in vitro antiplasmodial activity of some dihydrostilbenamides, phtalazinones, imidazo[2,1-a]isoindole and pyrimido[2,1-a]isoindole derivatives related to the natural dihydrostilbenoid isonotholaenic acid is reported. The evaluation was performed on cultures of F32 strain of Plasmodium falciparum and potent representative compounds were also evaluated in the ferriprotoporphyrin IX biomineralization inhibition test (FBIT). Compounds having the imidazo[2,1-a]isoindole skeleton were the most active and one compound of this group resulted to be as potent as chloroquine, but acting through a mechanism different that of the inhibition of heme biomineralization.

Leishmanicidal activity of some stilbenoids and related heterocyclic compounds

We have evaluated the leishmanicidal activity of some natural and semisynthetic dihydrostilbenoids and several compounds of other series of dihydrostilbamides, isoindoles, phthalazinones, imidazoisoindoles and pyrimidoisoindoles. The evaluation was performed in vitro, on cultures of cutaneous, mucocutaneous and visceral strains of Leishmania spp. The most potent and selective compounds of these series were the dihydrostilbene piperidides.