☆ 4.5 Article

SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2010)

期刊

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷 20, 期 5, 页码 1593-1597

出版社

PERGAMON-ELSEVIER SCIENCE LTD

DOI: 10.1016/j.bmcl.2010.01.083

关键词

SCD inhibitors; Desaturation index; Body weight gain prevention; Insulin and glucose sensitivity

类别

Chemistry, Medicinal Chemistry, Organic

向作者/读者索取更多资源

Protocol

Reagent

摘要

Elevated stearoyl-CoA desaturase (SCD) activity has been linked to a number of metabolic disorders including obesity and type II diabetes. Compound 3j, a potent SCD inhibitor (human HepG2 IC(50) = 1 nM) was identified from the optimization of a lead thiazole compound MF-152 with over 100-fold improvement in potency. In a 4-week chronic oral dosing at 0.2 mg/ kg, 3j gave a robust 24% prevention of body weight gain in mice fed on a high fat diet accompanied with an improved metabolic profile on insulin and glucose levels. (C) 2010 Elsevier Ltd. All rights reserved.

作者

我是这篇论文的作者

点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5

评分不足

次要评分

新颖性

-

重要性

-

科学严谨性

-

评价这篇论文

推荐

Article Endocrinology & Metabolism

Intermittent Versus Continuous Energy Restriction for Weight Loss and Metabolic Improvement: A Meta-Analysis and Systematic Review

Shasha He, Jiao Wang, Jie Zhang, Jixiong Xu

Summary: This study found that intermittent energy restriction (IER) was more beneficial for short-term weight loss and metabolic improvements in adults with overweight or obesity compared to continuous energy restriction (CER). Furthermore, longer randomized controlled trials (RCTs) are needed to confirm these findings.

OBESITY (2021)

添加到收藏夹

Article Endocrinology & Metabolism

Rate of Gestational Weight Gain and Glucose-Insulin Metabolism Among Hispanic Pregnant Women With Overweight and Obesity

Karen L. Lindsay, Lauren E. Gyllenhammer, Sonja Entringer, Pathik D. Wadhwa

Summary: Objective: The study aimed to determine the association between rate of gestational weight gain (rGWG) and glucose-insulin metabolism in Hispanic pregnant women with overweight and obesity. The findings revealed that rGWG was inversely associated with beta-cell function in a high-risk population of Hispanic pregnant women with overweight and obesity, potentially contributing to the development of type 2 diabetes.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2022)

添加到收藏夹

Article Endocrinology & Metabolism

Chronic circadian disruption on a high-fat diet impairs glucose tolerance

Kirsi-Marja Zitting, Ramalingam Vetrivelan, Robin K. Yuan, Nina Vujovic, Wei Wang, Sathyajit S. Bandaru, Stuart F. Quan, Elizabeth B. Klerman, Frank A. J. L. Scheer, Orfeu M. Buxton, Jonathan S. Williams, Jeanne F. Duffy, Clifford B. Saper, Charles A. Czeisler

Summary: This study examines the effects of circadian disruption on metabolism in both mice and humans. The results show that circadian disruption, even in the absence of significant sleep loss, has a negative impact on glucose metabolism in individuals consuming a high-fat diet. Reducing dietary fat intake may help protect against the metabolic consequences of chronic circadian disruption.

METABOLISM-CLINICAL AND EXPERIMENTAL (2022)

添加到收藏夹

Article Medicine, General & Internal

Gestational weight change in a diverse pregnancy cohort and mortality over 50 years: a prospective observational cohort study

Stefanie N. Hinkle, Sunni L. Mumford, Katherine L. Grantz, Pauline Mendola, James L. Mills, Edwina H. Yeung, Anna Z. Pollack, Sonia M. Grandi, Rajeshwari Sundaram, Yan Qiao, Enrique F. Schisterman, Cuilin Zhang

Summary: Gestational weight change is associated with mortality over 50 years later, with sustained excessive or reduced weight being associated with increased risk of cardiovascular and diabetes-related deaths.

LANCET (2023)

添加到收藏夹

Article Agriculture, Dairy & Animal Science

Effects of energy source in milk replacer on glucose metabolism of neonatal dairy calves

A. C. Welboren, B. Hatew, O. Lopez-Campos, J. P. Cant, L. N. Leal, J. Martin-Tereso, M. A. Steele

Summary: This study found that partially replacing lactose with fat in milk replacers can improve body weight gain and metabolic energy intake in dairy calves. Calves fed milk replacers with fat showed better insulin sensitivity than those fed high-lactose milk replacers.

JOURNAL OF DAIRY SCIENCE (2021)

添加到收藏夹

Article Cell Biology

Seasonal light hours modulate peripheral clocks and energy metabolism in mice

Lewin Small, Leonidas S. Lundell, Jo Iversen, Amy M. Ehrlich, Morten Dall, Astrid L. Basse, Emilie Dalbram, Ann N. Hansen, Jonas T. Treebak, Romain Barres, Juleen R. Zierath

Summary: Seasonal light affects energy metabolism by modulating the rhythmicity of food intake, rather than melatonin.

CELL METABOLISM (2023)

添加到收藏夹

Review Nutrition & Dietetics

Effects of Plant-Based Diets on Anthropometric and Cardiometabolic Markers in Adults: An Umbrella Review

Han Shi Jocelyn Chew, Felicia Kai Xin Heng, Si Ai Tien, Jie Yun Thian, Hui Shan Chou, Shaun Seh Ern Loong, Wei How Darryl Ang, Nicholas W. S. Chew, Ka-Hei Kenneth Lo

Summary: We conducted an umbrella review that consolidated evidence on the effects of plant-based diets on anthropometric and cardiometabolic outcomes. Seven systematic reviews with meta-analysis representing 51 primary studies were included. The findings suggested significant benefits of plant-based diets on weight, body mass index, waist circumference, fasting blood glucose, and low-density lipoprotein cholesterol. However, caution should be exercised in interpreting the results due to the low credibility of evidence and the limited generalizability of findings based on Western eating habits and traditions.

NUTRIENTS (2023)

添加到收藏夹

Article Chemistry, Medicinal

MLR-1023 Treatment in Mice and Humans Induces a Thermogenic Program, and Menthol Potentiates the Effect

Candida J. Rebello, Ann A. Coulter, Andrew G. Reaume, Weina Cong, Luke A. Cusimano, Frank L. Greenway

Summary: This study investigated a novel glucose-lowering medication, tolimidone (MLR-1023), and its synergy with menthol in weight management and metabolic control. Results demonstrated that MLR-1023 effectively reduces body weight and promotes thermogenesis, showing promising efficacy in both humans and mice.

PHARMACEUTICALS (2021)

添加到收藏夹

Review Nutrition & Dietetics

The Effects of Ketogenic Diet on Insulin Sensitivity and Weight Loss, Which Came First: The Chicken or the Egg?

Antonio Paoli, Antonino Bianco, Tatiana Moro, Joao Felipe Mota, Christianne F. Coelho-Ravagnani

Summary: In this review, the direct effects of ketogenic diets (KD) and the effects of weight loss induced by KDs on glycemic status in humans are discussed, along with the biochemical background and underlying mechanisms of KDs.

NUTRIENTS (2023)

添加到收藏夹

Article Endocrinology & Metabolism

Lack of Evidence for a Causal Role of Hyperinsulinemia in the Progression of Obesity in Children and Adolescents: A Longitudinal Study

Rana Halloun, Alfonso Galderisi, Sonia Caprio, Ram Weiss

Summary: In children and adolescents with obesity, exposure to hyperinsulinemia, greater insulin secretion, or low postprandial glucose is not associated with greater increases in the degree of obesity over 2-4 years.

DIABETES CARE (2022)

添加到收藏夹

Review Endocrinology & Metabolism

Cellular mechanism of diabetes remission by bariatric surgery

Jianping Ye, Yangxi Hu, Chengming Wang, Hongkai Lian, Zigang Dong

Summary: Bariatric surgery is an effective treatment for type 2 diabetes in obese patients. Surgery improves insulin sensitivity by inducing an energy deficit, correcting mitochondrial overload, and leading to diabetes remission.

TRENDS IN ENDOCRINOLOGY AND METABOLISM (2023)

添加到收藏夹

Article Nutrition & Dietetics

Beneficial effects of a combination of Clostridium cochlearium and Lactobacillus acidophilus on body weight gain, insulin sensitivity, and gut microbiota in high-fat diet-induced obese mice

Fei Yang, Wen-Jun Zhu, Paba Edirisuriya, Qing Ai, Kai Nie, Xiang-Ming Ji, Yong Li, Kequan Zhou

Summary: The combination of Clostridium cochlearium and Lactobacillus acidophilus showed beneficial effects on body weight control and glucose metabolism in high-fat diet-induced obese mice. This effect was potentially mediated by the modulation of gut microbiota, leading to reduced obesity and improved glucose homeostasis.

NUTRITION (2022)

添加到收藏夹

Article Medicine, General & Internal

Gestational weight gain in the REVAMP pregnancy cohort in Western India: Comparison with international and national references

Kamini Dangat, Sanjay Gupte, Girija Wagh, Sanjay Lalwani, Karuna Randhir, Shweta Madiwale, Hemlata Pisal, Vrushali Kadam, Shridevi Gundu, Nomita Chandhiok, Bharati Kulkarni, Sadhana Joshi, Caroline Fall, Harshpal Singh Sachdev

Summary: This study aimed to evaluate the trimester specific gestational weight gain (GWG) in Indian pregnant women and compare it with international and Indian reference data. The study found that Indian women had lower GWG compared to international standards, but higher GWG compared to Indian reference data. Maternal BMI, age, parity, hemoglobin concentrations, and height were found to be associated with GWG.

FRONTIERS IN MEDICINE (2022)

添加到收藏夹

Article Multidisciplinary Sciences

A comparison of the metabolic side-effects of the second-generation antipsychotic drugs risperidone and paliperidone in animal models

Heidi N. Boyda, Ric M. Procyshyn, Lurdes Tse, Jessica W. Y. Yuen, William G. Honer, Alasdair M. Barr

Summary: In preclinical models, both risperidone and paliperidone exhibited significant dose-dependent metabolic side effects in rats, including increased fasting glucose levels and insulin resistance. The differences between the two drugs were modest, with the most notable effect being on fasting glucose levels. Both drugs showed a dose-dependent decrease in the glucose infusion rate in the clamp test, indicating pronounced insulin resistance.

PLOS ONE (2021)

添加到收藏夹

Article Medicine, Research & Experimental

Metabolic flexibility across the spectrum of glycemic regulation in youth

Fida Bacha, Sara Klinepeter Bartz, Maurice Puyau, Anne Adolph, Susan Sharma

Summary: Metabolic flexibility is impaired in obese youth with dysglycemia, resulting from a defect in insulin sensitivity that limits substrate utilization. Factors such as fat-free mass, suppression of free fatty acids, and race/ethnicity contribute to the variance in metabolic flexibility.

JCI INSIGHT (2021)

添加到收藏夹

Article Chemistry, Medicinal

Thiazole analog as stearoyl-CoA desaturase 1 inhibitor

Chun Sing Li, Liette Belair, Jocelyne Guay, Renata Murgasva, Wayne Sturkenboom, Yeeman K. Ramtohul, Lei Zhang, Zheng Huang

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2009)

添加到收藏夹

Article Chemistry, Medicinal

2-Aryl benzimidazoles: Human SCD1-specific stearoyl coenzyme-A desaturase inhibitors

David A. Powell, Yeeman Ramtohul, Marie-Eve Lebrun, Renata Oballa, Sathesh Bhat, Jean-Pierre Falgueyret, Sebastien Guiral, Zheng Huang, Kathryn Skorey, Paul Tawa, Lei Zhang

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2010)

添加到收藏夹

Article Chemistry, Medicinal

Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: From systemic to liver-targeting inhibitors

Yeeman K. Ramtohul, David Powell, Jean-Philippe Leclerc, Serge Leger, Renata Oballa, Cameron Black, Elise Isabel, Chun Sing Li, Sheldon Crane, Joel Robichaud, Jocelyne Guay, Sebastien Guiral, Lei Zhang, Zheng Huang

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2011)

添加到收藏夹

Article Chemistry, Medicinal

Conversion of systemically-distributed triazole-based stearoyl-CoA desaturase (SCD) uHTS hits into liver-targeted SCD inhibitors

Jean-Philippe Leclerc, Jean-Pierre Falgueyret, Melina Girardin, Jocelyne Guay, Sebastien Guiral, Zheng Huang, Chun Sing Li, Renata Oballa, Yeeman K. Ramtohul, Kathryn Skorey, Paul Tawa, Hao Wang, Lei Zhang

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2011)

添加到收藏夹

Article Chemistry, Medicinal

Design and synthesis of potent, isoxazole-containing renin inhibitors

Pierre-Andre Fournier, Melissa Arbour, Elizabeth Cauchon, Austin Chen, Amandine Chefson, Yves Ducharme, Jean-Pierre Falgueyret, Sebastien Gagne, Erich Grimm, Yongxin Han, Robert Houle, Patrick Lacombe, Jean-Francois Levesque, Dwight MacDonald, Bruce Mackay, Dan McKay, M. David Percival, Yeeman Ramtohul, Rene St-Jacques, Sylvie Toulmond

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2012)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series

Nicolas Lachance, Yves Gareau, Sebastien Guiral, Zheng Huang, Elise Isabel, Jean-Philippe Leclerc, Serge Leger, Evelyn Martins, Christian Nadeau, Renata M. Oballa, Stephane G. Ouellet, David A. Powell, Yeeman K. Ramtohul, Geoffrey K. Tranmer, Thao Trinh, Hao Wang, Lei Zhang

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2012)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of potent and liver-selective stearoyl-CoA desaturase (SCD) inhibitors in an acyclic linker series

Nicolas Lachance, Sebastien Guiral, Zheng Huang, Jean-Philippe Leclerc, Chun Sing Li, Renata M. Oballa, Yeeman K. Ramtohul, Hao Wang, Jin Wu, Lei Zhang

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2012)

添加到收藏夹

Article Chemistry, Medicinal

3,4-Diarylpiperidines as potent renin inhibitors

Patrick Lacombe, Melissa Arbour, Renee Aspiotis, Elizabeth Cauchon, Austin Chen, Daniel Dube, Jean-Pierre Falgueyret, Pierre-Andre Fournier, Michel Gallant, Erich Grimm, Yongxin Han, Helene Juteau, Suzanna Liu, Christophe Mellon, Yeeman Ramtohul, Daniel Simard, Rene St-Jacques, Gavin Chit Tsui

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2012)

添加到收藏夹

Article Chemistry, Medicinal

Development of a Liver-Targeted Stearoyl-CoA Desaturase (SCD) Inhibitor (MK-8245) to Establish a Therapeutic Window for the Treatment of Diabetes and Dyslipidemia

Renata M. Oballa, Liette Belair, W. Cameron Black, Kelly Bleasby, Chi Chung Chan, Carole Desroches, Xiaobing Du, Robert Gordon, Jocelyne Guay, Sebastien Guiral, Michael J. Hafey, Emelie Hamelin, Zheng Huang, Brian Kennedy, Nicolas Lachance, France Landry, Chun Sing Li, Joseph Mancini, Denis Normandin, Alessandro Pocai, David A. Powell, Yeeman K. Ramtohul, Kathryn Skorey, Dan Sorensen, Wayne Sturkenboom, Angela Styhler, Deena M. Waddleton, Hao Wang, Simon Wong, Lijing Xu, Lei Zhang

JOURNAL OF MEDICINAL CHEMISTRY (2011)

添加到收藏夹

Review Chemistry, Multidisciplinary

Pd-catalyzed enantioselective aerobic oxidation of secondary alcohols: Applications to the total synthesis of alkaloids

Shyam Krishnan, Jeffrey T. Bagdanoff, David C. Ebner, Yeeman K. Ramtohul, Uttam K. Tambar, Brian M. Stoltz

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2008)

添加到收藏夹

Article Cell Biology

Restoring Methicillin-Resistant Staphylococcus aureus Susceptibility to β-Lactam Antibiotics

Christopher M. Tan, Alex G. Therien, Jun Lu, Sang H. Lee, Alexandre Caron, Charles J. Gill, Christian Lebeau-Jacob, Liliana Benton-Perdomo, Joao M. Monteiro, Pedro M. Pereira, Nathaniel L. Elsen, Jin Wu, Kathleen Deschamps, Mihai Petcu, Simon Wong, Etienne Daigneault, Susanne Kramer, Lianzhu Liang, Eugene Maxwell, David Claveau, John Vaillancourt, Kathryn Skorey, John Tam, Hao Wang, Timothy C. Meredith, Susan Sillaots, Lisa Wang-Jarantow, Yeeman Ramtohul, Eric Langlois, France Landry, John C. Reid, Gopal Parthasarathy, Sujata Sharma, Anastasia Baryshnikova, Kevin J. Lumb, Mariana G. Pinho, Stephen M. Soisson, Terry Roemer

SCIENCE TRANSLATIONAL MEDICINE (2012)

添加到收藏夹

Article Chemistry, Organic

Synthesis of Polycyclic Indolone and Pyrroloindolone Heterocycles via the Annulation of Indole- and Pyrrole-2-Carboxylate Esters with Arynes

Robert D. Giacometti, Yeeman K. Ramtohul

SYNLETT (2009)

添加到收藏夹

Article Chemistry, Organic

Synthesis of α,α-Disubstituted Benzocyclobutane Amino Acids through [2+2] Annulation of Benzyne with Dehydroalanine

Audrey Picard, Stephane Ciblat, Yeeman K. Ramtohul

SYNLETT (2020)

添加到收藏夹

Article Biochemical Research Methods

A Multiplexed Cell Assay in HepG2 Cells for the Identification of Delta-5, Delta-6, and Delta-9 Desaturase and Elongase Inhibitors

Lei Zhang, Yeeman Ramtohul, Sebastien Gagne, Angela Styhler, Hao Wang, Jocelyne Guay, Zheng Huang

JOURNAL OF BIOMOLECULAR SCREENING (2010)

添加到收藏夹

Article Chemistry, Medicinal

Design and synthesis of a library of C2-substituted sulfamidoadenosines to probe bacterial permeability

Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan

Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

添加到收藏夹

Article Chemistry, Medicinal

Design of MERS-CoV entry inhibitory short peptides based on helix-stabilizing strategies

Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang

Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

添加到收藏夹

Article Chemistry, Medicinal

Development of novel β2-adrenergic receptor agonists for the stimulation of glucose uptake - The importance of chirality and ring size of cyclic amines

Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman

Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

添加到收藏夹

Article Chemistry, Medicinal

Conformationally constrained potent inhibitors for enhancer of zeste homolog 2 (EZH2)

Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li

Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

添加到收藏夹

Article Chemistry, Medicinal

The potential of Rhein's aromatic amines for Parkinson's disease prevention and treatment: α-Synuclein aggregation inhibition and disaggregation of preformed fibers

Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang

Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

添加到收藏夹

Article Chemistry, Medicinal

Design, synthesis and biological evaluation of novel cationic liposomes loaded with melphalan for the treatment of cancer

Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla

Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2024)

添加到收藏夹

© Peeref 2019-2024. All rights reserved.