Synthesis and hypoglycemic activity of 4-substituted 3-mercaptopicolinic acids

Blank, Benoît; Nw, DiTullio; Deviney, L.; Roberts, JT; Magnani, Arthur; M, Billig; Hl, Saunders

doi:10.1021/jm00222a007

Cited by 7 publications

(6 citation statements)

References 8 publications

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“…The introduction of the C3 methyl group converted 5, a compound with hyperglycemic activity, to 1, a compound with potent hypoglycemic activity. The glycemic activity seen in the methanol and propanol series (2)(3)(4)(5)(6)(7) was not consistent with the above data, in that 3 and 6 with C3 alcohol side chains were most potent, whereas 1 with a C2 propanol side chain was more potent than 25 with a C3 propanol side chain. Similarly, introducing a C2 methyl group into 3 led to a compound (24) with no hypoglycemic activity.…”

Section: Discussionmentioning

confidence: 71%

“…In a series of pyridylmethanols (2-4), only 3 was hypoglycemic. In the propanol series (5)(6)(7), the 2 and 4 isomers 5 and 7 were weakly hyperglycemic, while the 3 isomer 6 was weakly hypoglycemic. All compounds were studied after oral doses of 150 mg/kg in fasted rats.…”

mentioning

confidence: 98%

“…A. Using the method of Marvel et al,205.3 g (0.039 mol) of 31 was reduced in 30 mL of HOAc by heating with 1.25 g (0.042 g-atom) of red P and 30 mL of 47% HI for 35 h. The cooled mixture was filtered; the filtrate was…”

mentioning

confidence: 99%

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Synthesis and hypoglycemic activity of pyridylalcohols

Blank¹,

DiTullio²,

Krog³

et al. 1979

J. Med. Chem.

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The potent hypoglycemic activity of 3-(3-methyl-2-pyridyl)propan-1-ol (1) prompted us to synthesize and study related structures. Some of the variables studied were the position of the methyl and alcohol side chains, the distance between the heterocyclic ring and the hydroxyl group, the effect of additional nuclear substitution, and the effects of branching and substitution on the alcohol side chain. The compounds were tested in 48-h fasted rats, usually at a dose of 150 mg/kg po. 1, the corresponding propionic acid 12, the acetate and methyl ether of 1 (22 and 23), and the 5-methyl analogue of 1 (29) were of comparable hypoglycemic potency. However, these compounds all caused a concomitant elevation of hepatic triglycerides and/or death in the test animals when observations were continued for 4--24 h.

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Section: Discussionmentioning

confidence: 71%

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confidence: 98%

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Synthesis and hypoglycemic activity of pyridylalcohols

Blank¹,

DiTullio²,

Krog³

et al. 1979

J. Med. Chem.

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“…Blank et al [19] reported that 3-mercapto-4-methylpicolinic acid (h, Figure 1) was one of very few compounds derived from 3-mercaptopicolinic acid (3-MPA) to have hypoglycemic activity. In order to find compounds with greater potency than 3-MPA, several 4-substituted 3-mercaptopicolinic acids (4-OMe, OC 6 H 5 , SMe, SH, C1, NH 2 , Et) were prepared and used for animal experiments.…”

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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“…Second, sequences that convert pyridines into N -oxides are followed by 4-selective nitration. Halopyridines are then formed directly by treatment with PHal 3 or P(O)Hal 3 reagents, or by displacing the nitro group with a nucleophilic halide and then reducing the N -oxide. , Requiring preinstalled functional groups, strong bases, oxidants, and highly acidic media limits the applicability of these approaches . As a result, there are considerably fewer commercial 4-halopyridines than other isomers, and those available can be prohibitively expensive.…”

Section: Introductionmentioning

confidence: 99%

Selective Halogenation of Pyridines Using Designed Phosphine Reagents

et al. 2020

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Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine C-H precursors are lacking. We designed a set of heterocyclic phosphines that are selectively installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. The study concludes that both tuning the phosphonium electrophilicity and pyridine substitution patterns influence the efficiency of the carbon-halogen bond-forming step.

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Synthesis and hypoglycemic activity of 4-substituted 3-mercaptopicolinic acids

Cited by 7 publications

References 8 publications

Synthesis and hypoglycemic activity of pyridylalcohols

Synthesis and hypoglycemic activity of pyridylalcohols

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

Selective Halogenation of Pyridines Using Designed Phosphine Reagents

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