Synthesis and hypoglycemic activity of pyridylalcohols

Blank, Benjamin; DiTullio, Nicholas W.; Krog, A. J.; Saunders, Harry L.

doi:10.1021/jm00193a017

Cited by 8 publications

(3 citation statements)

References 21 publications

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“…Finally, the preparation of pyridine 23 in good yield demonstrates the compatibility of alkene functionality with the cycloaddition and chlorination conditions. Structural assignments for the pyridine annulation products are based on NMR spectroscopic analyses, and data for the known pyridines 19 , 20 , 22 , and 24 are fully consistent with that previously reported for these compounds.…”

Section: Resultssupporting

confidence: 78%

Synthesis of Substituted Pyridines via Regiocontrolled [4 + 2] Cycloadditions of Oximinosulfonates

Renslo

Danheiser

1998

J. Org. Chem.

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Diels−Alder cycloadditions of oximinosulfonate 8 with a variety of 1,3-dienes proceed with regiochemistry opposite to that observed with conventional imino dienophiles, providing expeditious synthetic routes to substituted pyridines, tetrahydropyridines, and pyrrolines. The oximinosulfonate 8 is prepared in one convenient synthetic operation from Meldrum's acid and reacts with conjugated dienes at −78 °C in the presence of 2 equiv of dimethylaluminum chloride to afford [4 + 2] cycloadducts in good to excellent yield. Exposure of these cycloadducts to the action of NaOMe and N-chlorosuccinimide in methanol−THF at room temperature then produces substituted pyridines. The utility of this new two-step annulation protocol is demonstrated in total syntheses of the pyridine alkaloids fusaric acid and (S)-(+)-fusarinolic acid. Heating the [4 + 2] cycloadducts derived from 8 in a mixture of acetonitrile and pH 7 phosphate buffer induces an unusual Stieglitz-type rearrangement leading to the formation of interesting spirobicyclic pyrrolines.

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Section: Resultssupporting

confidence: 78%

Synthesis of Substituted Pyridines via Regiocontrolled [4 + 2] Cycloadditions of Oximinosulfonates

Renslo

Danheiser

1998

J. Org. Chem.

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“…Blank et al [20] performed several structural modifications of 3-(3-methyl-2-pyridyl)-1-propanol (i, Figure 1), changing the positions of the methyl and alcohol side chains, the distance between the heterocycle and hydroxyl groups, and adding substituents, and they proved the hypoglycemic activity through animal experiments. Compounds were tested in rats fasted for 48 h at a dose of 150 mg/kg.…”

Section: Screening Of Hypoglycemic Heterocyclesmentioning

confidence: 99%

Research Progress on the Synthesis and Structure-Activity Relationship of Five Hypoglycemic Active Heterocycles Based on Dipeptidyl Peptidase 4 (DPP-4) Target Design

Kong¹,

Yang²,

Zhou³

et al. 2022

Chinese Journal of Organic Chemistry

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Recently, diabetes has gradually become a main life-threatening disease in China. Drug targets for the treatment of diabetes mainly include dipeptidyl peptidase 4 (DPP-4), adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPARγ) receptor and so on, in which targeted drug research targeting DPP-4 is a hot spot in recent years. DPP-4 inhibitor is a drug for the treatment of type 2 diabetes, and its biggest advantage is that it is not easy to induce hypoglycemia and increase weight. It is reported that the currently available DPP-4 targeted drugs can cause adverse reactions, such as pancreatitis and hypersensitivity. Therefore, it is worth further studying to continue to develop new hypoglycemic drugs for DPP-4 inhibitors to avoid adverse reactions. According to the systematic literature review, the potential heterocyclic structures with hypoglycemic activity are summarized and through computer molecular simulation docking, five kinds of heterocyclic structures with high hypoglycemic activity and easy synthesis are finally screened out based on DPP-4 target design. The synthesis routes and structure-activity relationships are summarized and analyzed, which provides a research basis for the development of safe, efficient and novel hypoglycemic drugs for DPP-4 inhibitors in the future. Keywords diabetes; dipeptidyl peptidase 4 (DPP-4) inhibitor; molecular docking; synthesis methods; structure-activity relationship

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“…Attempts to alter the selectivity of this reaction failed, which indicated that competition between proton abstraction from the methylene group of ethyl orthobromoacetate and bromine displacement occurs. Treatment of the anion of (5) with bromoacetaldehyde diethyl acetal, however, gave high isolated yields of (12). It was found to be essential to use 1 equiv.…”

Section: (Ii) Methyl 3-(2-methoxy-4-pyridyl)propionatementioning

confidence: 99%

Synthesis of 2-substituted 4-pyridylpropionates. Part 2. Alkylation approach

Adger¹,

Ayrey²,

Bannister³

et al. 1988

J. Chem. Soc., Perkin Trans. 1

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A synthesis of methyl 3-(2-methoxy-4-pyridy1)propionate ( Z ) , a key intermediate in the synthesis of the potent long-acting histamine H,-receptor antagonist SK&F 93574 ( I ) , is described. The key step in the synthesis of compound (1 ) involves alkylation of 2-methoxy-4-methylpyridine (5) with sodium chloroacetate in the presence of sodamide. The scope and limitations of the alkylation is investigated using a variety of electrophiles. The application of this reaction to other 2-substituted 4-methylpyridines is also discussed.

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Synthesis and hypoglycemic activity of pyridylalcohols

Cited by 8 publications

References 21 publications

Synthesis of Substituted Pyridines via Regiocontrolled [4 + 2] Cycloadditions of Oximinosulfonates

Synthesis of Substituted Pyridines via Regiocontrolled [4 + 2] Cycloadditions of Oximinosulfonates

Research Progress on the Synthesis and Structure-Activity Relationship of Five Hypoglycemic Active Heterocycles Based on Dipeptidyl Peptidase 4 (DPP-4) Target Design

Synthesis of 2-substituted 4-pyridylpropionates. Part 2. Alkylation approach

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