Extracurricular laboratory:new discovery of 2-(3-(4-Bromo-2-fluorobenzyl)-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid

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Remedies for vertebral canal stenosis

The present invention relates to a preventive and/or therapeutic agent for spinal canal stenosis comprising aldose reductase inhibitory compounds. A representative example of aldose reductase inhibitory compounds is the compound represented by formula (I): [image] wherein all the symbols represent the same meaning as described in the specification; a salt of its acid when R3a represents hydrogen, or solvate thereof The therapeutic agent of the present invention is effective for prevention and/or therapy for spinal canal stenosis and the like, such as lumbar spinal canal stenosis.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N846 – PubChem

Properties and Exciting Facts About 2-(3-(4-Bromo-2-fluorobenzyl)-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid

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Inhibition of hexonate dehydrogenase and aldose reductase from bovine retina by sorbinil, statil, M79175 and valproate.

Aldose reductase inhibitors (A.R.I.s), developed as potentially therapeutic agents for the treatment of complications of long-term diabetes, were found to be potent inhibitors of aldose reductase (ALR2) partially purified from bovine retina (IC50 values: Statil 0.89 microM, Sorbinil 2 microM, M79175 greater than 1 microM). These compounds varied, however, in their ability to inhibit hexonate dehydrogenase (ALR1), a closely related enzyme isolated from the same source (IC50 values: Statil greater than 1 microM, Sorbinil 3.9 microM, M79175 0.18 microM). Statil and Sorbinil were active against ALR2 at very low concentrations (approx. 5% inhibition at 100 pM), but did not inhibit ALR1 at less than or equal to 10 nM. In contrast, M79175 (structurally very similar to Sorbinil) and M7HEQ (a flavonoid) were preferential inhibitors of ALR1. Valproate, a compound of value in the treatment of epilepsies, was a poor inhibitor of ALR2 (18% at 1 mM). Furthermore, valproate was found to be a relatively poor inhibitor of ALR1, particularly in comparison with M79175.

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Phthalazine – Wikipedia,
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Penetration and performance testing of the HP? Mole for the InSight Mars mission

During the development and the qualification of the Heat Flow Physical Properties Package (HP?) instrument (developed by the German Aerospace Center), which is part of the NASA Mars mission InSight, its self-propelling subsurface probe, the HP? Mole was used in several penetration tests. Here, the performance of the Mole to reach the target depth, to avoid or overcome obstacles on its path, and its directional stability in the subsurface is elaborated. The different test beds and set ups are described and the results are presented. The deep penetration tests (DPT), with the purpose to reach the target depth, are the most important performance tests and therefore the results are investigated in more detail in section 2. Full functional tests (FFT), which showed the performance and degradation of the mechanism inside the Mole, are presented in section 3. Additional penetration and life cycle tests are described in section 4. The testing has demonstrated that the HP? Mole meets all of its penetration requirements with margin.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N924 – PubChem

Properties and Exciting Facts About 2-(3-(4-Bromo-2-fluorobenzyl)-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid

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Current status of the chemistry and synthesis of natural antimalarial compounds and natural substances used to alleviate symptoms of diabetes (aldose reductase and a-glucosidase inhibitors)

Atropine, camptothecin, cocaine, digitoxin, digoxin, morphine, pilocarpine, quinine, taxol, vinblastine and vincristine, among others, are important drugs obtained from higher plants and are used clinically. They have also served as lead compounds for the synthesis and modification of more effective and safer drugs, in many cases. In this chapter, drugs used as antimalarial compounds and for the complications of diabetes (aldose reductase and alpha-glucosidase inhibitors) will be discussed. Natural product chemists have isolated as little as 1.0 mg of pure compounds from natural sources and have been able to determine their structures using high resolution instrumental techniques. Organic chemists have synthesized thousands of compounds to produce one new drug on the basis of natural product leads, and pharmacologists and biochemists have tested their biological activity. Recently chemists and pharmacologists have worked together to develop techniques for studying structure-activity relationships using computer graphics and have designed new drugs. Biochemists, molecular biologists and pharmacologists have identified many receptors on which drugs act. Thus, mechanisms of drug action at the molecular level are being identified. From the accumulation of these results structure-activity relationships will lead to the preparation of thousands of useful compounds. We must produce drugs in these ways, because we cannot rely on solely on the limited amount of active compounds produced naturally in plants, in many cases, for a number of reasons. However we need to employ plant extracts themselves, because there are millions of people who cannot buy expensive synthetic drugs in the world and these extracts are widely used by them.

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Phthalazine – Wikipedia,
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Method for the prophylactic treatment of cataracts

The present invention is directed to a method for the prophylactic treatment of cataract. The method involves the administration of a compound of Formula I STR1wherein V, W and X are selected from the group consisting of hydro, hydroxyl, alkoxy, halo, an ester, an ether, a carboxylic acid group, a pharmaceutically acceptable salt of a carboxylic acid group, and –SR, in which R is hydrogen or an alkyl group, Y is selected from the group consisting of oxygen, sulfur, C(OH), and C O, and Z is selected from the group consisting of hydro and C(O)OR 1, wherein R 1 is an alkyl, or an analogue or prodrug thereof or a pharmaceutically acceptable salt of any of the foregoing to an animal, such as a mammal, in particular a human, in an amount sufficient to treat cataracts prophylactically. The compound of Formula I is preferably genistein.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N841 – PubChem

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

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Combination therapy for diabetes, obesity and cardiovascular diseases using GDF-8 inhibitors

A method of treating obesity, cardiovascular diseases, and disorders of insulin metabolism in a subject, comprising administering to the subject a therapeutically effective amount of a GDF-8 inhibitor, and a therapeutically effective amount of at least one other therapeutic agent which treats the targeted syndrome.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N842 – PubChem

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

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A highly specific aldose reductase inhibitor, ethyl 1-benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate, and its congeners

Ethyl 1-benzyl-3-hydroxy-2(5H)-oxopyrrole-4-carboxylate (1, EBPC) is a potent and specific inhibitor of aldose reductase. It was >4000X more potent in its inhibition of rat lens aldose reductase than the closely related rat or pig kidney aldehyde reductase, thus making it the most selective inhibitor of a NADPH-dependent carbonyl reductase identified to date. In agreement with this observation, it was found to be a highly potent inhibitor of aldose reductase from rat sciatic nerve with >98% inhibition at 1 muM, but it was practically devoid of activity against aldehyde reductases from rat liver and brain. Inhibition of aldose reductase was mixed type for glyceraldehyde (K(i) = 8.0 X 10-8 M) and noncompetitive for NADPH (K(i) = 1.70 X 10-8 M). Its potential as an in vitro tool to quantitate monomeric aldo/keto reductase activities in crude tissue extracts is presented. Structure-activity relationships emerging from synthetic modifications of EBPC are discussed. Several modifications were found to be active in vitro against aldose reductase from human placenta and in vivo in a rat model of diabetic complications, but none was more potent than EBPC.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N892 – PubChem

More research is needed about 2-(3-(4-Bromo-2-fluorobenzyl)-4-oxo-3,4-dihydrophthalazin-1-yl)acetic acid

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METHODS INVOLVING ALDOSE REDUCTASE INHIBITORS

Embodiments of the invention include methods and compositions involving aldose reductase inhibitors for the treatment of inflammation, including uveitis and asthma.

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Phthalazine | C8H6N844 – PubChem

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Properties of ICI 128,436, a novel aldose reductase inhibitor, and its effects on diabetic complications in the rat

ICI 128,436 (3-(4-bromo-2-fluorobenzyl)-4-oxo-3H-phthalazin-1-ylacetic acid) is a chemically novel, potent inhibitor of aldose reductase. It inhibits partially purified aldose reductase isolated from a number of sources including human tissue (human lens -IC50 2.0 x 10-8 mol/L). Dulcitol accumulation in erythrocytes and sciatic nerves of galactose loaded rats was inhibited by five days of treatment with ICI 128,436 (oral ED50’s 2.21 mg/kg and 8.56 mg/kg, respectively). On oral administration for five days to streptozotocin diabetic rats, ICI 128,436, reduced sorbitol levels in sciatic nerve, lens, retina, and renal cortex. The ED50 for inhibition of nerve sorbitol accumulation was 5 mg/kg. The effect of a single dose of ICI 128,436 in diabetic rats was prolonged, with little increase in nerve sorbitol for 48 hours. No tolerance to the ability of ICI 128,436 to reduce nerve sorbitol was found on treatment for 74 days. ICI 128,436 was effective in rodent models of the neural and lenticular complications of diabetes. At doses as low as 25 mg/kg/d it completely prevented the development of cataracts in diabetic rats. The deterioration in motor nerve conduction velocity found in diabetic rats was ameliorated by treatment with ICI 128,436 (3.125 mg/kg/d). Thus, ICI 128,436 constitutes a chemically novel aldose reductase inhibitor that is now being assessed for therapeutic value in the diabetic patient.

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Phthalazine – Wikipedia,
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Synthetic Route of 72702-95-5, 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, 72702-95-5, molcular formula is C17H12BrFN2O3, introducing its new discovery.

Hydantoin bioisosteres. In vivo active spiro hydroxy acetic acid aldose reductase inhibitors

The hypothesis that clinical side effects of the aldose reductase inhibitor (ARI) sorbinil were related to its hydantoin ring led to a bioisosteric analysis and replacement of the hydantoin by a spiro hydroxy acetic acid moiety as in 40. These hydroxy acids, compared to hydantoins, showed a similar potency increase on chroman 2-methyl substitution, a similar orthogonal relationship of acidic to aromatic moieties, and similar ARI enantioselectivity. In this series the six-membered spiro hydroxy acetic acid anion array is a bioisostere for a spiro hydantoin anion and leads to ARIs with excellent in vivo activity. In vitro and in vivo activity was improved over 40 by chroman cis 2-methylation as in 4 and by aromatic 6,7-halogen substitution. Compounds with the best acute in vivo activity in rats were compared for chronic in vivo activity. The highest tissue levels and best chronic in vivo activities were found in the racemic 6,7-dichloro and 6- fluoro-7-chloro analogues 18 and 23. ARI activity was enantioselective for 58 and 60, the 2R,4R-enantiomers of 18 and 23. 7-Chloro-6-fluoro-cis-4-hydroxy- 2(R)-methyl-chroman-4-acetic acid (60) was selected for phase 1 clinical trials and did not exhibit sorbinil-like hypersensitivity side effects.

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