Some scientific research about 253-52-1

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A Synopsis of the Properties and Applications of Heteroaromatic Rings in Medicinal Chemistry

Five- and six-membered heteroaromatic rings and their benzo-fused homologues are well established as important structural elements in drug design and are well represented in approved drugs. The key properties of these heterocycles that are of?interest to medicinal chemists include lipophilicity, pKa, aromaticity, ionization potential, H-bond acceptor, and H-bond donor (N?H, O?H, C?H) capability, electron withdrawing effects, dipole values, and bond angles. The judicious and productive application of azoles and azines in drug design requires an understanding of the intrinsic physical chemical properties of the individual heterocycles and how these interact with substituents. In this article, the key properties of azole and azine heterocycles are summarized followed by a synopsis of applications where some of these factors play a role in drug?target interactions and/or potency.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N284 – PubChem

Archives for Chemistry Experiments of 2-(3-(4-Bromo-2-fluorobenzyl)-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid

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Cardiac autonomic neuropathy: Risk factors, diagnosis and treatment

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus (DM) that is strongly associated with approximately five-fold increased risk of cardiovascular mortality. CAN manifests in a spectrum of things, ranging from resting tachycardia and fixed heart rate (HR) to development of “silent” myocardial infarction. Clinical correlates or risk markers for CAN are age, DM duration, glycemic control, hypertension, and dyslipidemia (DLP), development of other microvascular complications. Established risk factors for CAN are poor glycemic control in type 1 DM and a combination of hypertension, DLP, obesity, and unsatisfactory glycemic control in type 2 DM. Symptomatic manifestations of CAN include sinus tachycardia, exercise intolerance, orthostatic hypotension (OH), abnormal blood pressure (BP) regulation, dizziness, presyncope and syncope, intraoperative cardiovascular instability, asymptomatic myocardial ischemia and infarction. Methods of CAN assessment in clinical practice include assessment of symptoms and signs, cardiovascular reflex tests based on HR and BP, short-term electrocardiography (ECG), QT interval prolongation, HR variability (24 h, classic 24 h Holter ECG), ambulatory BP monitoring, HR turbulence, baroreflex sensitivity, muscle sympathetic nerve activity, catecholamine assessment and cardiovascular sympathetic tests, heart sympathetic imaging. Although it is common complication, the significance of CAN has not been fully appreciated and there are no unified treatment algorithms for today. Treatment is based on early diagnosis, life style changes, optimization of glycemic control and management of cardiovascular risk factors. Pathogenetic treatment of CAN includes: Balanced diet and physical activity; optimization of glycemic control; treatment of DLP; antioxidants, first of all a-lipoic acid (ALA), aldose reductase inhibitors, acetyl- L-carnitine; vitamins, first of all fat-soluble vitamin B1; correction of vascular endothelial dysfunction; prevention and treatment of thrombosis; in severe cases-treatment of OH. The promising methods include prescription of prostacyclin analogues, thromboxane A2 blockers and drugs that contribute into strengthening and/or normalization of Na+, K+-ATPase (phosphodiesterase inhibitor), ALA, dihomo-gamma-linolenic acid (DGLA), omega-3 polyunsaturated fatty acids (omega-3 PUFAs), and the simultaneous prescription of ALA, omega-3 PUFAs and DGLA, but the future investigations are needed. Development of OH is associated with severe or advanced CAN and prescription of nonpharmacological and pharmacological, in the foreground midodrine and fludrocortisone acetate, treatment methods are necessary.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N911 – PubChem

Extracurricular laboratory:new discovery of 253-52-1

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Silver(i) complexes with quinazoline and phthalazine: Synthesis, structural characterization and evaluation of biological activities

New silver(i) complexes with quinazoline (qz) and phthalazine (phtz), [Ag(NO3)(qz)]n (1) and {[Ag(CH3CN)]2(mu-phtz)2}[BF4]2 (2), have been synthesized and structurally characterized by using different spectroscopic and single-crystal X-ray diffraction techniques. The obtained results revealed that the reaction of AgNO3 with qz at room temperature in a 2 :1 molar ratio led to the formation of the polynuclear complex 1. However, the reaction of AgBF4 with phtz under the same experimental conditions resulted in the formation of the dinuclear complex 2. The solution behaviour and air/light stability of these silver(i) complexes have been investigated. The complexes 1 and 2, along with the silver(i) salts used for their synthesis, were evaluated by in vitro antimicrobial studies against a panel of microbial strains that lead to many skin and soft tissue, respiratory, wound, and nosocomial infections. The obtained results indicate that all tested silver(i) compounds have good antibacterial activity with MIC values in the range from 1.5 to 15.6 mug mL-1 against the investigated strains. On the other hand, their antifungal activity against Candida albicans was moderate. In order to determine the therapeutic potential of 1 and 2, their antiproliferative effect on the normal human lung fibroblast cell line MRC5, hemolytic effect on red blood cells and embryotoxicity on zebrafish (Danio rerio) have also been evaluated.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N390 – PubChem

Discovery of 2-(3-(4-Bromo-2-fluorobenzyl)-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid

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Aldose reductase, ocular diabetic complications and the development of topical Kinostat

Diabetes mellitus (DM) is a major health problem with devastating effects on ocular health in both industrialized and developing countries. The control of hyperglycemia is critical to minimizing the impact of DM on ocular tissues because inadequate glycemic control leads to ocular tissue changes that range from a temporary blurring of vision to permanent vision loss. The biochemical mechanisms that promote the development of diabetic complications have been extensively studied. As a result, a number of prominent biochemical pathways have been identified. Among these, the two-step sorbitol pathway has been the most extensively investigated; nevertheless, it remains controversial. To date, long-term pharmacological studies in animal models of diabetes have demonstrated that the onset and development of ocular complications that include keratopathy, retinopathy and cataract can be ameliorated by the control of excess metabolic flux through aldose reductase (AR). Clinically the alleles of AR have been linked to the rapidity of onset and severity of diabetic ocular complications in diabetic patient populations around the globe. In spite of these promising preclinical and human genetic rationales, several clinical trials of varying durations with structurally diverse aldose reductase inhibitors (ARIs) have shown limited success or failure in preventing or arresting diabetic retinopathy. Despite these clinical setbacks, topical ARI Kinostat promises to find a home in clinical veterinary ophthalmology where its anticipated approval by the FDA will present an alternative treatment paradigm to cataract surgery in diabetic dogs. Here, we critically review the role of AR in diabetes mellitus-linked ocular disease and highlight the development of Kinostat for cataract prevention in diabetic dogs. In addition to the veterinary market, we speculate that with further safety and efficacy studies in humans, Kinostat or a closely related product could have a future role in treating diabetic keratopathy.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N870 – PubChem

A new application about 6-Amino-2,3-dihydrophthalazine-1,4-dione

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Chapter 4 The immunochemical/photochemical interface

In this chapter we have seen that the immunochemical reaction and chemiluminescent reaction can be interfaced in a variety of ways though chiefly by coupling the chemiluminescent reactant itself (direct chemiluminescence labelling) to an immunoreactant, or by coupling another component of a chemiluminescent reaction other than the chemiluminescent molecule itself (indirect chemiluminescence labelling). It can be seen that the indirect labelling systems are incapable of achieving the level of simplicity offered by certain direct labelling systems, though some indirect labelling systems offer an equivalent level of sensitivity. The chemical techniques required to conjoin the chemiluminescent and immunochemical reactions are relatively well established though do not always permit substantial retention of light emission and immunoreactivity respectively. This is often dictated by the chemical properties of the species to be conjugated themselves. We have briefly considered the role of bioluminescent systems here even though they have yet to be widely accepted in the context of chemiluminescence immunoassay. Their true potential may yet be realized by the interface with genetic engineering techniques which will permit controlled biosynthesis of the appropriate enzymes.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N669 – PubChem

Brief introduction of 253-52-1

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Effect of commonly used organic solvents on Aldehyde oxidase-mediated Vanillin, Phthalazine and Methotrexate oxidation in human, rat and mouse liver subcellular fractions

1. Aldehyde oxidase (AOX) is a cytosolic molybdoflavoprotein enzyme widely distributed across many tissues. In this study, we report the effect of commonly used organic solvents such as dimethyl sulfoxide (DMSO), acetonitrile (ACN), methanol and ethanol on AOX activity in human, rat and mouse liver S9 fractions using vanillin, phthalazine and methotrexate as probe substrates. 2. Methanol was found to be the most potent solvent in inhibiting vanillic acid and 1-phthalazinone formation in comparison to DMSO, ACN and ethanol across the species tested, except 7-hydroxy methotrexate. 3. Treatment with these solvents at approximate IC50 (% v/v) concentrations showed significant reduction in Clint and Vmax of the probe substrates and also resulted in different effects on Km across the species. 4. Marked differences in the activity and affinity towards AOX were observed with different probe substrates with methotrexate showing least activity and affinity as compared to vanillin and phthalazine. 5. Overall, AOX activity seemed to be more resilient to the presence of organic solvents at higher concentrations in human and rodent species. These results suggest that low concentrations of organic solvents are acceptable for in vitro incubations involving AOX-mediated metabolism.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N64 – PubChem

Top Picks: new discover of Phthalazine

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Synthesis, molecular modelling and anticancer evaluation of new pyrrolo[1,2-b]pyridazine and pyrrolo[2,1-a]phthalazine derivatives

Two new series of heterocyclic derivatives with potential anticancer activity, in which a pyrrolo[1,2-b]pyridazine or a pyrrolo[2,1-a]phthalazine moiety was introduced in place of the 3?-hydroxy-4?-methoxyphenyl ring of phenstatin have been synthesised and their structure-activity relationship (SAR) was studied. Fourteen of the new compounds were evaluated for their in vitro cytotoxic activity by National Cancer Institute (NCI) against 60 human tumour cell lines panel. The best five compounds in terms of in vitro growth inhibition were screened in the second stage five dose-response studies, three of them showing a very good antiproliferative activity with GI50<100 nM on several cell lines including colon, ovarian, renal, prostate, brain and breast cancer, melanoma and leukemia. Docking experiments on the biologically active compounds showed a good compatibility with the colchicine binding site of tubulin. A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 253-52-1 Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N348 – PubChem

Discovery of 3682-14-2

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Congenital heart block and immune mediated sensorineural hearing loss: Possible cross reactivity of immune response

Immune-mediated sensorineural hearing loss may complicate systemic autoimmune diseases. We have previously reported the presence of antibodies directed against inner ear antigens in patients with Cogan syndrome, a disease characterized by sudden hearing loss and interstitial keratitis. Such autoantibodies cross-react with an epitope of SSA/Ro60 protein. Anti-Ro/SSA antibodies in pregnant women cross the placenta and reach the fetal tissues inducing an immune-mediated damage of the cardiac conduction system. We wanted to evaluate whether mothers with anti-Ro/SSA antibodies who gave birth to children with congenital heart block have antibodies directed against inner ear antigens and whether these antibodies are connected with the presence of immune-mediated sensorineural hearing loss. We did not find anti-inner ear antibodies in the majority of the mothers. On the contrary a 13-year-old boy with congenital heart block and sensorineural hearing loss was positive for the presence of anti-inner ear antigens antibodies. Moreover his serum was positive for the presence of anti-Ro60 peptide antibodies but did not recognize the entire protein Ro60 (TROVE2), a behaviour similar to that of sera from patients with Cogan syndrome. In conclusion the data obtained so far show that anti-inner ear antibodies do not recognize the entire protein TROVE2 and do not support the hypothesis that such antibodies may be involved in the pathogenesis of congenital heart block.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N525 – PubChem

Top Picks: new discover of 3682-14-2

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Related Products of 3682-14-2, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 3682-14-2, molcular formula is C8H7N3O2, introducing its new discovery.

Experimental evidence of the reciprocal oxidation of Bovine Serum Albumin and Linoleate in aqueous solution, initiated by HO? free radicals

An investigation of radiation-induced oxidation of aqueous bovine serum albumin (BSA) in the presence of linoleate (LH) at pH 10.5 has been carried out in order to better understand the respective oxidative processes involved in both lipid and protein phases. Solutions containing BSA (15 mumol L-1) and linoleate (15-600 mumol L-1) below the critical micellar concentration (cmc = 2000 mumol L-1), have been irradiated by gamma-rays (137Cs) at radiation doses ranging from 10 to 400 Gy (dose rate 9.5 Gy min-1). It can be noticed that, in the absence of BSA, the main hydroperoxides formed from HO?-induced linoleate oxidation below the cmc, do not exhibit a conjugated dienic structure. This was also verified in the presence of BSA. Selected chemical markers of oxidation have been monitored: non-conjugated dienic hydroperoxides and conjugated dienes (without hydroperoxide function) for linoleate oxidation, and carbonyl groups for BSA oxidation. We have shown that for the lowest linoleate concentration (15 mumol L-1) in the presence of BSA (15 mumol L-1), the formation of conjugated dienes was not observed, meaning that LH was not exposed to HO? radicals attack. However, non-conjugated dienic lipid hydroperoxides were simultaneously detected, indicating that LH was secondarily oxidised by BSA oxidised species. Moreover, the oxidation of linoleate was found to be enhanced by the presence of BSA. For the highest linoleate concentration (600 mumol L-1), the expected protection of BSA by LH was not observed, even if LH monomers were responsible for the total scavenging of HO? radicals. In this latter case, the formation of non-conjugated dienic lipid hydroperoxides was lower than expected. Those results showed that BSA was not oxidised by the direct action of HO? radicals but was undergoing a secondary oxidation by non-dienic lipid hydroperoxides and/or lipid radical intermediates, coming from the HO?-induced linoleate oxidation.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N542 – PubChem

New explortion of 72702-95-5

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Spiro[fluoreneisothiazolidin]one dioxides: New aldose reductase and L- hexonate dehydrogenase inhibitors

The first examples of spiro[fluorene-9,4′- and -9,5′-isothiazolidin]one dioxides (1 and 2) were synthesized and screened for activity as aldose reductase and L-hexonate dehydrogenase inhibitors. Compared to compounds 1, and 9,5′-compounds 2, synthesized from fluorene-9-sulfonamides by alkylation at C(9) with ethyl bromoacetate followed by cyclization, were more active, but relatively nonselective, inhibitors of aldose reductase and L-hexonate dehydrogenase, with IC50 values for in vitro inhibition of both enzymes on the order of 10-7-10-8 M. However, the isomeric 9,4′-compounds 1, prepared by alkylation of fluorene-9-carboxylic acid esters with bromo- or iodomethanesulfonamide followed by cyclization, were more selective inhibitors of L-hexonate dehydrogenase with IC50 values of about 10-6 M.

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Reference£º
Phthalazine – Wikipedia,
Phthalazine | C8H6N858 – PubChem