Design, synthesis and bioevaluation of 3-oxo-6-aryl-2,3-dihydropyridazine-4-carbohydrazide derivatives as novel xanthine oxidase inhibitors

Zhang, Lichao; Wang, Sibo; Yang, Minmin; Shi, Ailong; Wang, He; Guan, Qı; Bao, Kai; Zhang, Weige

doi:10.1016/j.bmc.2019.03.027

Cited by 16 publications

(8 citation statements)

References 24 publications

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“…Gratifyingly, the protocol exhibited scalability with a moderate yield of 53 %. Additionally, derivatization of 2 c was carried out under reflux conditions in the presence of hydrazine hydrochloride and delivered the product 2 ca [28] . Next, 2 c was subjected to hydrogenation to achieve the formation of fully reduced ketone derivative 2 cb (Scheme 5).…”

Section: Methodsmentioning

confidence: 99%

Electricity Driven 1,3‐Oxohydroxylation of Donor‐Acceptor Cyclopropanes: a Mild and Straightforward Access to β‐Hydroxy Ketones

2021

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An unprecedented external oxidant-free electrochemical protocol for 1, 3-oxohydroxylation of donor-acceptor cyclopropane is disclosed. The strategy encompasses the activation of the labile π-electron cloud of the aryl ring to cleave the strained C sp 3 À C sp 3 bond of cyclopropane to afford the β-hydroxy ketones via insertion of molecular oxygen. More significantly, based on the detailed mechanistic investigations and cyclic voltammetry experiments, a plausible mechanism is proposed.The magnificent journey of the most strained carbocycle named cyclopropane began long back in the 1970s. [1] The fundamentals laid by the frontiers have enabled the scientific community to exploit them for the construction of several complex molecular architectures cleverly. Bearing the ring strain of 115 KJ mol À 1 with an inefficient orbital overlap induces a significant amount of π-character in the bent CÀ C bonds of Cylclopropanes. [2] Further, the introduction of the donor and acceptor groups at the vicinal position of these CÀ C bonds induces a push-pull effect which polarizes the cycloalkane. [3] The previous decade has encountered a huge renaissance in the area of donor-acceptor cyclopropanes (DACs). [4] However, most of these documented protocols rely on the concept of Lewis [5] or Bronsted acid [6] catalysis, which cleaves the CÀ C bond in a heterolytic fashion and renders a zwitterionic species. [4] These 1,3-dipole species have been utilized for several cycloadditions, [7] rearrangements, [8] and ring-opening reactions. [9] Among them, 1,3-bifunctionalization of these DACs are still rare and relatively underexplored. However, there are several reports which demonstrate that these 1,3-dipoles can be seized with amines, [10a] azides, [10b] phenols, [10c] thiols [10d] etc. wherein, the ensuing anion traps the proton. In 2011, Sparr and Gilmour manifested the enantioselective 1,3-dichlorination of cyclopropane carbaldehyde in an organocatalytic fashion. [11] Later, in 2014, Werz and coworkers disclosed the ring-opening 1,3-dichlorination in the presence of iodobenzene dichloride (Scheme 1a). [12a] Followed by this, in 2017, the same group documented the reactivity of DACs with chalcogenyl chloride and bromides (Scheme 1b). [12b-c] In continuation to the endeav-[a

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Section: Methodsmentioning

confidence: 99%

Electricity Driven 1,3‐Oxohydroxylation of Donor‐Acceptor Cyclopropanes: a Mild and Straightforward Access to β‐Hydroxy Ketones

2021

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“…The presence of the cyano group and o -isopropyl also elevates the potential. 64 Another research group took the lead from compound 10 and developed 5-phenylisoxazole-3-carboxylic acid analogues and screened their xanthine oxidase inhibitory potential. Compound 15 was found potent in the test with an IC 50 value of 0.36 μM.…”

Section: Preclinical Synthetic Xanthine Oxidase Inhibitorsmentioning

confidence: 99%

Past, present and future of xanthine oxidase inhibitors: design strategies, structural and pharmacological insights, patents and clinical trials

Singh,

Sharma

et al. 2023

RSC Med. Chem.

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“…Among these compounds, 43 exhibited outstanding XO inhibitory activity with an IC 50 value of 1.03 μM. Furthermore, it was displayed in molecular docking and in vitro studies that the hydrazide moiety promoted XO inhibitory potency by the formation of H‐bonds with Arg880, Glu802 amino acid residues, and Mos3004 residue in the active pocket (Zhang, Wang, et al, 2019). Rullo et al, 2023 discovered non‐purine‐type compounds which showed potent inhibition against XO.…”

Section: Synthetic Compoundsmentioning

confidence: 99%

Therapeutic voyage of synthetic and natural xanthine oxidase inhibitors

Agrawal,

Arya,

Kushwah

2023

Chem Biol Drug Des

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Xanthine oxidase (XO) inhibitors are commonly used to treat gout, nephropathy, and renal stone diseases related to hyperuricemia. However, recent research has shown that these inhibitors may also have potential benefits in preventing vascular diseases, including those affecting the cerebrovasculature. This is due to emerging evidence suggesting that serum uric acid is involved in the growth of cardiovascular disease, and XO inhibition can reduce oxidative stress in the vasculature. There is a great interest in the development of new XO inhibitors for the treatment of hyperuricemia and gout. The present review discusses the many synthetic and natural XO inhibitors that have been developed which are found to have greater potency.

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Design, synthesis and bioevaluation of 3-oxo-6-aryl-2,3-dihydropyridazine-4-carbohydrazide derivatives as novel xanthine oxidase inhibitors

Cited by 16 publications

References 24 publications

Electricity Driven 1,3‐Oxohydroxylation of Donor‐Acceptor Cyclopropanes: a Mild and Straightforward Access to β‐Hydroxy Ketones

Electricity Driven 1,3‐Oxohydroxylation of Donor‐Acceptor Cyclopropanes: a Mild and Straightforward Access to β‐Hydroxy Ketones

Past, present and future of xanthine oxidase inhibitors: design strategies, structural and pharmacological insights, patents and clinical trials

Therapeutic voyage of synthetic and natural xanthine oxidase inhibitors

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