Design and biological evaluation of tetrahydropyridine derivatives as novel human GPR119 agonists

Zuo, Zeping; Chen, Miaomiao; Shao, Xiaoni; Qian, Xinying; Liu, Xiaocong; Zhou, Xia; Xiang, Jiawei; Deng, Pengchi; Li, Yan; Jie, Hui; Liu, Chunqi; Cen, Xiaobo; Xie, Yongmei; Zhao, Yinglan

doi:10.1016/j.bmcl.2019.126855

Cited by 6 publications

(2 citation statements)

References 15 publications

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“…The starting tetrazolylanilines were obtained by known methods and their characteristics correspond to the literature data: 3-(1H-tetrazol-1-yl)aniline 1a, 42 3-(5methyl-1H-tetrazol-1-yl)aniline 1b, 43 4-(1H-tetrazol-1yl)aniline 1c, 44 4-(5-methyl-1H-tetrazol-1-yl)aniline 1d, 45 4-(5-(methylthio)-1H-tetrazol-1-yl)aniline 1e, 46 3-methyl-4-(1H-tetrazol-1-yl)aniline 1f. 47…”

Section: General Procedure Physical and Spectral Datamentioning

confidence: 88%

The (1H-Tetrazol-1-yl)arenediazonium Salts as Convenient Reagents for Quinones Arylation: Synthesis of 1,3-Benzoxathiol-2-ones and Naphtho[2,1-d][1,3]oxathiol-2-ones Bearing (1H-Tetrazol-1-yl)phenyl Motif

Pokhodylo¹,

Martyak²,

Tupychak³

et al. 2023

ChChT

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A convenient two-step method for the synthesis of novel 1,3-benzoxathiol-2-ones and naphtho[2,1-d][1,3]oxathiol-2-ones bearing (1H-tetrazol-1-yl)phenyl motif was developed. As a key step of the synthesis, an arylation of quinones (1,4-benzoquinone, 1,4-naphtho-quinones) with the (1H-tetrazol-1-yl)arenediazonium salts was studied and efficient protocols were elaborated to obtain a variety of substituted ((1H-tetrazol-1-yl)phenyl) benzo/naphtho-1,4-quinones in good to excellent yields. An alternative synthesis of ((1H-tetrazol-1-yl)phenyl) naphtho-1,4-quinones via Diels-Alder reaction of tetrazolylphenyl-1,4-benzoquinones was demonstrated. The prepared benzo/naphtho-1,4-quinones readily react with thiourea at room temperature in the presence of a strong mineral acid to form intermediate isothiuronium salts, which cyclize with high yields to condense 1,3-oxathiol-2-ones under heating.

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Section: General Procedure Physical and Spectral Datamentioning

confidence: 88%

The (1H-Tetrazol-1-yl)arenediazonium Salts as Convenient Reagents for Quinones Arylation: Synthesis of 1,3-Benzoxathiol-2-ones and Naphtho[2,1-d][1,3]oxathiol-2-ones Bearing (1H-Tetrazol-1-yl)phenyl Motif

Pokhodylo¹,

Martyak²,

Tupychak³

et al. 2023

ChChT

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“…Based on systematic optimization of the general structure MBX-2982, novel terazole-tetrahydropyridine derivatives as novel human GPR119 agonists 81a,b were obtained by Zuo et al (Figure 17). They showed high GPR119 agonist activity in vitro {81a (EC 50 4.9 nM) and 81b (EC 50 8.8 nM)}, and in vivo compound 81a showed a hypoglycemic effect and may have an effect on improving basal metabolic rate in DIO mice [75]. As can be seen from Figure 16, low-molecular GPR119 ligands usually contain polynitrogen heterocyclic fragments (triazole, oxadiazole, and tetrazole) linked to other aromatic cycles.…”

Section: G Protein-coupled Receptor (Gpcr) Agonistsmentioning

confidence: 99%

Tetrazoles and Related Heterocycles as Promising Synthetic Antidiabetic Agents

Trifonov,

Ostrovskii

2023

IJMS

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Tetrazole heterocycle is a promising scaffold in drug design, and it is incorporated into active pharmaceutical ingredients of medications of various actions: hypotensives, diuretics, antihistamines, antibiotics, analgesics, and others. This heterocyclic system is metabolically stable and easily participates in various intermolecular interactions with different biological targets through hydrogen bonding, conjugation, or van der Waals forces. In the present review, a systematic analysis of the activity of tetrazole derivatives against type 2 diabetes mellitus (T2DM) has been performed. As it was shown, the tetrazolyl moiety is a key fragment of many antidiabetic agents with different activities, including the following: peroxisome proliferator-activated receptors (PPARs) agonists, protein tyrosine phosphatase 1B (PTP1B) inhibitors, aldose reductase (AR) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, G protein-coupled receptor (GPCRs) agonists, glycogen phosphorylases (GP) Inhibitors, α-glycosidase (AG) Inhibitors, sodium glucose co-transporter (SGLT) inhibitors, fructose-1,6-bisphosphatase (FBPase) inhibitors, IkB kinase ε (IKKε) and TANK binding kinase 1 (TBK1) inhibitors, and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). In many cases, the tetrazole-containing leader compounds markedly exceed the activity of medications already known and used in T2DM therapy, and some of them are undergoing clinical trials. In addition, tetrazole derivatives are very often used to act on diabetes-related targets or to treat post-diabetic disorders.

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