Discovery of novel 2-(pyridine-2-yl)-1H-benzimidazole derivatives as potent glucokinase activators

Ishikawa, Makoto; Nonoshita, Katsumasa; Ogino, Yukiko; Nagae, Yoshikazu; Tsukahara, Daisuke; Hosaka, Hideka; Maruki, Hiroko; Ohyama, Seiichi; Yoshimoto, Riki; Sasaki, Kaori; Nagata, Yasufumi; Eiki, Jun-ichi; Nishimura, Teruyuki

doi:10.1016/j.bmcl.2009.05.038

Cited by 51 publications

(17 citation statements)

References 17 publications

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“…Compound 52 surfaced out as an attractive molecule for further modification to improve GK potency and to develop further structurally diverse GKAs. Compound 52 led to the discovery of a potent and metabolically stable compound 53(R) [76]. Kwak et al reported synthesis of aminobenzimidazole derivatives having a phenylcyclohexyl acetic acid group as depicted in Fig.37 and evaluated them for anti-obesity and anti-diabetic activity.…”

Section: Anti-diabetic Activitymentioning

confidence: 98%

Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review

Yadav

Ganguly

2015

European Journal of Medicinal Chemistry

347

141

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Section: Anti-diabetic Activitymentioning

confidence: 98%

Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review

Yadav

Ganguly

2015

European Journal of Medicinal Chemistry

347

141

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“…Данные о безопасности активаторов ГК, полученные в экспериментах на животных, нельзя непосредственно экстраполировать на человека. Необходимы дальнейшие детальные исследования этой проблемы [20].…”

Section: положительные эффекты активаторов гкunclassified

Glucokinase activators — a promising class of antidiabetic drugs

Спасов¹,

Косолапов²,

Babkov³

et al. 2018

Probl Endokrinol (Mosk)

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Type 2 diabetes mellitus is an urgent problem of the modern healthcare. Despite a wide choice of oral hypoglycemic drugs, today there is a great need to create and introduce into clinical practice new, effective, and safe drugs for the treatment of diabetes. One of the promising targets for the creation of new antidiabetics is a glucokinase. It has an exceptionally high influence on glucose homeostasis, serving as a glucose “sensor” in pancreatic β-cells and controlling the rate of glycogen synthesis in the liver. In the present work, the molecular-genetic structure of the enzyme, as well as its interrelation with the organs and tissues of the organism, is presented. The modern ideas about activators of glucokinase as a promising class of antidiabetic drugs are outlined, their hypoglycemic and general antidiabetic effects proved in preclinical and clinical studies are considered. The most advanced activators of glucokinase, undergoing clinical trials, are indicated.

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“…The role of glucokinase in glucose metabolism have been emphasized by loss-of-function mutations in the gene coding for glucokinase, linked to maturity-onset diabetes of the youth type 2 (MODY 2 characterized by impaired glucose responsiveness of β cells, decreased glycogen accumulation and increased hepatic glucose production after meals). Current studies are testing whether glucokinase activators will restore appropriated glucose sensing, that is, insulin secretion in response to glucose, hepatic glucose output, and GLP1 secretion [185]. Finally, the fuel sensor adenosine monophosphate–activated protein kinase in the hypothalamus regulates energy homeostasis by sensing nutritional and hormonal signals.…”

Section: Pharmacologic Therapy For Glycemic Controlmentioning

confidence: 99%

Management of type 2 diabetes: evolving strategies for the treatment of patients with type 2 diabetes

et al. 2011

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The prevalence of type 2 diabetes continues to increase at an alarming rate around the world, with even more people being affected by prediabetes. Although the pathogenesis and long-term complications of type 2 diabetes are fairly well known, its treatment has remained challenging, with only half of the patients achieving the recommended hemoglobin A1c target. This narrative review explores the pathogenetic rationale for the treatment of type 2 diabetes, with the view of fostering better understanding of the evolving treatment modalities. The diagnostic criteria including the role of hemoglobin A1c in the diagnosis of diabetes are discussed. Due attention is given to the different therapeutic maneuvers and their utility in the management of the diabetic patient. The evidence supporting the role of exercise, medical nutrition therapy, glucose monitoring, and antiobesity measures including pharmacotherapy and bariatric surgery is discussed. The controversial subject of optimum glycemic control in hospitalized and ambulatory patients is discussed in detail. An update of the available pharmacologic options for the management of type 2 diabetes is provided with particular emphasis on newer and emerging modalities. Special attention has been given to the initiation of insulin therapy in patients with type 2 diabetes, with explanation of the pathophysiologic basis for insulin therapy in the ambulatory diabetic patient. A review of the evidence supporting the efficacy of the different preventive measures is also provided.

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Discovery of novel 2-(pyridine-2-yl)-1H-benzimidazole derivatives as potent glucokinase activators

Cited by 51 publications

References 17 publications

Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review

Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review

Glucokinase activators — a promising class of antidiabetic drugs

Management of type 2 diabetes: evolving strategies for the treatment of patients with type 2 diabetes

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