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Synthesis and in vitro evaluation of hydrazinyl phthalazines against malaria parasite, Plasmodium falciparum

In this report, we describe the synthesis of 1-(Phthalazin-4-yl)-hydrazine using bronsted acidic ionic liquids and demonstrate their ability to inhibit asexual stage development of human malaria parasite, Plasmodium falciparum. Through computational studies, we short-listed chemical scaffolds with potential binding affinity to an essential parasite protein, dihydroorotate dehydrogenase (DHODH). Further, these compounds were synthesized in the lab and tested against P. falciparum. Several compounds from our library showed inhibitory activity at low micro-molar concentrations with minimal cytotoxic effects. These results indicate the potential of hydralazine derivatives as reference scaffolds to develop novel antimalarials.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N421 – PubChem

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The synthesis of 6,9-bis[(aminoalkyl)amino] substituted benzo[g]quinoxaline-, benzo[g]quinazoline- and benzo[g]phthalazine-5,10- diones via regiospecific displacements

The synthesis of 6,9-difluoro substituted benzo[g]quinoxaline-5,10-diones (3A), benzo[g]quinazoline-5,10-diones (3B) and benzo[g]phthalazine-5,10- diones (3C) have been accomplished. Treatment of 3A, 3B or 3C with diamines or N-(t-butoxycarbonyl)ethylenediamine led to the corresponding 6,9- bis[(aminoalkyl)amino]-substituted analogues related to 2A, 2B and 2C, respectively. The mono-substituted derivatives 4h and 4i could be isolated from displacements commencing from 3A. A competitive ring-opening of the pyrimidine ring of 2C occurred during the reaction with N,N- dimethylethylenediamine. Removal of the BOC-protecting group from 2Ac led to the hydrochloride salt 2Ab. A novel synthetic pathway to 6,9- dihydroxybenzo[g]phthalazine-5,10-dione (21a) was developed. Conversion of 21a to the ditosylate 21b was readily accomplished. Treatment of 21b with N,N-dimethylethylenediamine or N-(t-butoxycarbonyl)ethylenediamine led to 2Ca and 2Cc, respectively. Removal of the BOC-protecting group from 2Cc with trifluoroacetic acid followed by ion-exchange led to the hydrochloride salt 2Cb. Treatment of ditosylate 21b with N-(t-butoxycarbonyl)ethylenediamine also led to the mono-substituted analogue 25a along with a small amount of the O-S cleavage product 25b. Treatment of 25a with N,N- dimethylethylenediamine led to the unsymmetrically substituted derivative 25c which was converted into the trifluoroacetate salt 25d.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N241 – PubChem

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New pyrrolo[2,1-a]phthalazine derivatives by one-pot three-component synthesis

The synthesis of the pyrrolo[2,1-a]phthalazine derivatives was performed by an efficient one-pot three-component reaction starting from phthalazine, 2-bromoacetophenones and nonsymmetrical and symmetrical acetylenic dipolarophiles in 1,2-epoxybutane as both reaction medium and HBr scavenger. The structure of the compounds was assigned by IR and NMR spectroscopy. Georg Thieme Verlag Stuttgart New York.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N136 – PubChem

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Photoredox-Mediated Minisci-type Alkylation of N-Heteroarenes with Alkanes with High Methylene Selectivity

We report a highly efficient and chemoselective Minisci-type alkylation reaction of N-heteroarenes with alkanes under the reagent control of a hypervalent iodine oxidant PFBI-OH. In addition to the high reactivity, PFBI-OH demonstrated a high steric sensitivity for H abstraction of alkanes. This reaction is selective for more sterically accessible secondary C-H bonds over weaker tertiary C-H bonds. High selectivity toward penultimate methylene groups was observed for a wide range of acyclic alkanes.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N255 – PubChem

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Synthesis of aza-naphthindolizinedione derivatives

A series of aza-naphthindolizinedione derivatives, such as indolizinoquinolinedione derivatives, indolizinophthalazinedione derivatives and indolizinoquinoxalinedione derivatives were designed and synthesized. The synthetic pathway was also proposed.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N401 – PubChem

Some scientific research about 6-Amino-2,3-dihydrophthalazine-1,4-dione

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Relative contributions of mitochondria and NADPH oxidase to deoxycorticosterone acetate-salt hypertension in mice

We assessed the relative contribution of the mitochondrial respiratory chain and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase to deoxycorticosterone acetate (DOCA)-salt hypertension in mice. The daily mean arterial pressure was monitored by radiotelemetry in DOCA-salt-treated mice given vehicle or the mitochondrial respiratory chain complex I inhibitor rotenone. This treatment produced remarkable attenuation of DOCA-salt hypertension. Similar results were obtained with other inhibitors of mitochondrial function, including 5-hydroxydecanoate (specific for mitochondrial potassium-ATP channels), benzylguanidine (complexes I and III), and the cell-permeable manganese tetrakis (4-benzoic acid) porphyrin (a mimic of mitochondrial superoxide dismutase). In parallel with the blood pressure-lowering effect of rotenone, the DOCA-salt-induced increases in urinary 8-isoprostane excretion and in reactive oxygen species production of isolated kidney mitochondria were both significantly attenuated. Conversely, the DOCA-salt-induced reduction of urinary nitrate/nitrite excretion was significantly elevated. Following DOCA-salt treatment, mice deficient in NADPH oxidase subunits gp91phox or p47phox exhibited a partial attenuation of the hypertensive response at early but not later time points. Thus, the mitochondrial respiratory chain is a major source of oxidative stress in DOCA-salt hypertension, whereas NADPH oxidase may have a relatively minor role during the early stage of hypertension.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N663 – PubChem

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A Ganoderma-Derived Compound Exerts Inhibitory Effect Through Formyl Peptide Receptor 2

Formyl peptide receptors (FPRs) are G protein-coupled receptors (GPCRs) widely expressed in neutrophils and other phagocytes. FPRs play important roles in host defense, inflammation, and the pathogenesis of infectious and inflammatory diseases. Because of these functions, FPRs are potential targets for anti-inflammatory therapies. In order to search for potentially novel anti-inflammatory agents, we examined Ganoderma (Lingzhi), a Chinese medicinal herbs known for its anti-inflammatory effects, and found that compound 18 (C18) derived from Ganoderma cochlear could limit the inflammatory response through FPR-related signaling pathways. Further studies showed that C18 could bind to FPR2 and induce conformation change of the receptor that differed from the conformational change induced by the pan-agonist, WKYMVm. C18 inhibited at the receptor level and blocked WKYMVm signaling through FPR2, resulting in reduced superoxide production and compromised cell chemotaxis. These results identified for the first time that a Ganoderma-derived component with inhibitory effects that acts through a G protein-coupled receptor FPR2. Considering its less than optimal IC50 value, further optimization of C18 would be necessary for future applications.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N651 – PubChem

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NOVEL INHIBITOR COMPOUNDS OF PHOSPHODIESTERASE TYPE 10A

The present invention relates to novel compounds of the formula I which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders

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Phthalazine – Wikipedia,
Phthalazine | C8H6N696 – PubChem

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Radical intramolecular arylation of pyridinium salts: A straightforward entry to 7-hydroxypyrido[2,1-a]isoquinolinylium salts

The synthesis of 7-hydroxypyrido[2,1-a]isoquinolinylium salts can be achieved in moderate yields by intramolecular radical arylation of pyridinium salts obtained from substituted pyridines and o-bromophenacyl bromides. The synthesis of 7-hydroxypyrido[2,1-a]isoquinolinylium salts can be achieved in moderate yields by intramolecular radical arylation on pyridinium salts obtained from substituted pyridines and o-bromophenacyl bromides.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N100 – PubChem

Archives for Chemistry Experiments of Phthalazine

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Silver nanoparticles: Therapeutical uses, toxicity, and safety issues

The promises of nanotechnology have been realized to deliver the greatest scientific and technological advances in several areas. The biocidal activity of Metal nanoparticles in general and silver nanoparticles (AgNPs) depends on several morphological and physicochemical characteristics of the particles. Many of the interactions of the AgNPs with the human body are still poorly understood; consequently, the most desirable characteristics for the AgNPs are not yet well established. Therefore, the development of nanoparticles with well-controlled morphological and physicochemical features for application in human body is still an active area of interdisciplinary research. Effects of the development of technology of nanostructured compounds seem to be so large and comprehensive that probably it will impact on all fields of science and technology. However, mechanisms of safety control in application, utilization, responsiveness, and disposal accumulation still need to be further studied in-depth to ensure that the advances provided by nanotechnology are real and liable to provide solid and consistent progress. This review aims to discuss AgNPs applied in biomedicine and as promising field for insertion and development of new compounds related to medical and pharmacy technology. The review also addresses drug delivery, toxicity issues, and the safety rules concerning biomedical applications of silver nanoparticles. 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1931-1944, 2014

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Phthalazine – Wikipedia,
Phthalazine | C8H6N132 – PubChem