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Aldose reductase as a drug target for treatment of diabetic nephropathy: Promises and challenges

Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus and the leading cause of end stage renal disease. One of the key pathways activated in DN is the polyol pathway, in which glucose is converted to sorbitol (a relatively nonmetabolizable sugar) by the enzyme aldose reductase (AR). Shunting of glucose into this pathway causes disruption to glucose metabolism and subsequently damages the tissues via increased oxidative stress, protein kinase c activation and production of advanced glycation end products (AGE) in the kidney. This review aims to provide a comprehensive overview of the AR enzyme structure, substrate specificity and topology in normal physiology; to elaborate on the deleterious effects of AR activation in DN; and to summarize the potential therapeutic benefits and major challenges associated with AR inhibition in patients with DN.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N863 – PubChem

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Investigations of reactions of selected azaarenes with radicals in water. 2. Chlorine and bromine radicals

The halogen radicals that react with azaarenes are produced by the photooxidation of halogenide anions with hydroxyl and sulfate radicals and exist as complexes of the radical and the respective halogenide anion in the aqueous phase. The main reaction products of the reactions are identified, and in the case of the bromine radicals, the second order rate constants are determined. Oxidation takes place according to the different redox potentials of the two reactants and is especially observed for chlorine radicals. A typical product spectrum comparable with that in reactions with hydroxyl and sulfate radicals has been found. The formation of some oxidation products in reactions of bromine radicals is in contradistinction to the oxidation potentials of the azaarenes and can be understood only by the reaction of their excited states. The halogenation is the main reaction of the azaarenes. Halogenation products of both, the benzene and the pyridine/diazine rings, have been found. The halogenation of the pyridine/diazine ring again requires the reaction of excited states. The majority of derivatives is halogenated in substitution reactions, but in the reaction of benzo[h]quinoline, addition is also observed. The resonance energy per electron is responsible for the change in the halogenation mechanism from substitution to addition.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N66 – PubChem

Archives for Chemistry Experiments of 763114-26-7

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PHTHALAZINONE COMPOUND

4-(4-Fluoro-3-(4-methoxypiperidine-1-carbonyl)benzyl)phthalazin-1(2H)-one as crystalline Form C.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N744 – PubChem

Brief introduction of Phthalazine

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Comparative study on the interaction of two binuclear Pt (II) complexes with human serum albumin: Spectroscopic and docking simulation assessments

Human serum albumin (HSA) principally tasks as a transport carrier for a vast variety of natural compounds and pharmaceutical drugs. In the present study, two structurally related binuclear Pt (II) complexes containing cis, cis-[Me2Pt (mu-NN) (mu-dppm) PtMe2] (1), and cis, cis-[Me2Pt(mu-NN)(mu dppm) Pt((CH2)4)] (2) in which NN?=?phthalazine and dppm?=?bis (diphenylphosphino) methane were used to investigate their interaction with HSA, using UV?Vis absorption spectroscopy, fluorescence, circular dichroism and molecular dynamic analyses. The spectroscopic results suggest that upon binding to HSA, the binuclear Pt (II) complexes could effectively induce structural alteration of this protein. These complexes can bind to HSA with the binding affinities of the following order: complex 2?>?complex 1. Moreover, the thermodynamic parameters of binding between these complexes and HSA suggested the existence of entropy-driven spontaneous interaction, which mostly dominated with the hydrophobic forces. The ANS fluorescence results also indicated that two binuclear Pt (II) complexes were competing for the binding to the hydrophobic regions on HSA. In addition, competitive displacement assay and docking simulation study revealed that complexes 1 and 2 bind to the drug binding sites II and I on HSA, respectively. Furthermore, complex 2, with the higher binding affinity for HSA, shows more denaturing effect on this protein. Considering the protein structural damages in the pathway of harmful side effects of platinum drugs, complex 1 with the moderate binding affinity and low denaturing effect might be of high significance.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N397 – PubChem

Extended knowledge of Phthalazine

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Surgical Cleavage of Unstrained C(sp3)?C(sp3) Bonds in General Alcohols for Heteroaryl C?H Alkylation and Acylation

We reported herein a predictable and surgical cleavage of carbon-carbon bond in alcohols. A wide range of 1, 2 and 3 alcohols including sugars and steroids without ring strain or steric hindrance were all compatible with this system. Also it offered a green and practical strategy for generation of alkyl/acyl radicals using alcohols as the sources. Besides, the features of visible-light-initiation, catalyst and metal free, excellent selectivity and mild conditions make it valuable and attractive. (Figure presented.).

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Phthalazine – Wikipedia,
Phthalazine | C8H6N476 – PubChem

Top Picks: new discover of Phthalazine

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A ‘push-pull’ tropylium-fused aminoporphyrazine

Crossover Linstead macrocyclization of cycloheptatrienylmaleonitrile and (dimethylamino)-maleonitrile gave access to an unsymmetrical (A3B) porphyrazine bearing six peripheral amino substituents and a fused cycloheptatrienyl ring. Subsequent hydride abstraction gave a tropylium-fused aminoporphyrazine, which contains both strongly electron-donating and withdrawing groups and thus can be labelled as a ‘push-pull’ macrocycle. Detailed structural studies of this novel porphyrazine are described.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N373 – PubChem

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Syntheses of substituted 2,4-dioxo-thienopyrimidin-1-acetic acids and their evaluation as aldose reductase inhibitors

A series of 2,4-dioxo-thieno[2,3-d], [3,2-d] and [3,4-d]pyrimidin-1-acetic acids (2) with a benzyl moiety at the N-3 position were prepared and tested in vitro for aldose reductase inhibitory activity against partially purified enzyme from rat lens. Some of these compounds were also evaluated for inhibition of sorbitol accumulation in the sciatic nerve or lens of streptozotocin-induced diabetic rats in vivo. Among the synthesized compounds, several showed potent aldose reductase inhibitory activity with IC50s in the 10-8 M range. Particularly, the potencies of non-substituted thieno- (2a and 2aa), 5-methylthieno- (2c), 5,6-dimethylthieno- (2g), 6-isopropylthieno- (2j and 2k), 6-chlorothienopyrimidine (2q) and benzothienopyrimidine (2ac) analogs were approximately equipotent ot FK-366 (1A) and Ponalrestat (1B) as references. Although most compounds were inactive in vivo, 2 compounds, 2k and 2q, possessed moderate in vivo activity.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N898 – PubChem

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Organocatalysis in Inert C-H Bond Functionalization

As two coexisting and fast-growing research fields in modern synthetic chemistry, the merging of organocatalysis and C-H bond functionalization is well foreseeable, and the joint force along this line has been demonstrated to be a powerful approach in making inert C-H bond functionalization more viable, predictable, and selective. In this review, we provide a comprehensive summary of organocatalysis in inert C-H bond functionalization over the past two decades. The review is arranged by types of inert C-H bonds including alkane C-H, arene C-H, and vinyl C-H as well as those activated benzylic C-H, allylic C-H, and C-H bonds alpha to the heteroatom such as nitrogen and oxygen. In each section, the discussion is classified by the explicit organocatalytic mode involved.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N352 – PubChem

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A one-pot radioiodination of aryl amines: Via stable diazonium salts: Preparation of 125I-imaging agents

An operationally simple, one-pot, two-step tandem procedure that allows the incorporation of radioactive iodine into aryl amines via stable diazonium salts is described. The mild conditions are tolerant of various functional groups and substitution patterns, allowing late-stage, rapid access to a wide range of 125I-labelled aryl compounds and SPECT radiotracers.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N828 – PubChem

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Photoelectrochemical C?H Alkylation of Heteroarenes with Organotrifluoroborates

A photoelectrochemical method for the C?H alkylation of heteroarenes with organotrifluoroborates has been developed. The merger of electrocatalysis and photoredox catalysis provides a chemical oxidant-free approach for the generation and functionalization of alkyl radicals from organotrifluoroborates. A variety of heteroarenes were functionalized using primary, secondary, and tertiary alkyltrifluoroborates with excellent regio- and chemoselectivity.

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Phthalazine – Wikipedia,
Phthalazine | C8H6N492 – PubChem