The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Alakananda Hajra - One of the best experts on this subject based on the ideXlab platform.

Steven B Coffey - One of the best experts on this subject based on the ideXlab platform.

  • route selection and optimization in the synthesis of two Imidazopyridine inhibitors of dgat 2
    Organic Process Research & Development, 2018
    Co-Authors: Scott Bader, Gary E Aspnes, Jianwei Bian, Steven B Coffey, Shawn Cabral, Qifang Li, Matthew S. Dowling, Michael Herr, Dilinie P Fernando, Wenhua Jiao
    Abstract:

    The scalable syntheses of two Imidazopyridine inhibitors of the enzyme diacylglycerol acyltransferase 2 (DGAT-2) are described. 6-Chloro-3-nitro-2-aminopyridine was the starting material for the convergent synthesis of the central Imidazopyridine ring. Differentiation in reactivity of the C2- and C3-nitrogen substituents on the pyridine ring and the development of mild cyclodehydration conditions to form the imidazole ring were critical problems that were addressed to deliver a 3-kg batch of compound 1 (PF-06424439) and a 0.1-kg batch of compound 2 (PF-06450561).

  • discovery and optimization of Imidazopyridine based inhibitors of diacylglycerol acyltransferase 2 dgat2
    Journal of Medicinal Chemistry, 2015
    Co-Authors: Kentaro Futatsugi, Gary E Aspnes, Scott Bader, Jianwei Bian, Philip A. Carpino, Shawn Cabral, Daniel W Kung, David Hepworth, Markus Boehm, Steven B Coffey
    Abstract:

    The medicinal chemistry and preclinical biology of Imidazopyridine-based inhibitors of diacylglycerol acyltransferase 2 (DGAT2) is described. A screening hit 1 with low lipophilic efficiency (LipE) was optimized through two key structural modifications: (1) identification of the pyrrolidine amide group for a significant LipE improvement, and (2) insertion of a sp3-hybridized carbon center in the core of the molecule for simultaneous improvement of N-glucuronidation metabolic liability and off-target pharmacology. The preclinical candidate 9 (PF-06424439) demonstrated excellent ADMET properties and decreased circulating and hepatic lipids when orally administered to dyslipidemic rodent models.

Sourav Jana - One of the best experts on this subject based on the ideXlab platform.

Guang Liang - One of the best experts on this subject based on the ideXlab platform.

  • Inhibition of inflammation and oxidative stress by an Imidazopyridine derivative X22 prevents heart injury from obesity.
    Journal of cellular and molecular medicine, 2016
    Co-Authors: Yuanyuan Qian, Gaozhi Chen, Yali Zhang, Peng Zhong, Kesong Peng, Xuemei Chen, Guang Liang
    Abstract:

    Inflammation and oxidative stress plays an important role in the development of obesity-related complications and cardiovascular disease. Benzimidazole and Imidazopyridine compounds are a class of compounds with a variety of activities, including anti-inflammatory, antioxidant and anti-cancer. X22 is an Imidazopyridine derivative we synthesized and evaluated previously for anti-inflammatory activity in lipopolysaccharide-stimulated macrophages. However, its ability to alleviate obesity-induced heart injury via its anti-inflammatory actions was unclear. This study was designed to evaluate the cardioprotective effects of X22 using cell culture studies and a high-fat diet rat model. We observed that palmitic acid treatment in cardiac-derived H9c2 cells induced a significant increase in reactive oxygen species, inflammation, apoptosis, fibrosis and hypertrophy. All of these changes were inhibited by treatment with X22. Furthermore, oral administration of X22 suppressed high-fat diet-induced oxidative stress, inflammation, apoptosis, hypertrophy and fibrosis in rat heart tissues and decreased serum lipid concentration. We also found that the anti-inflammatory and anti-oxidative actions of X22 were associated with Nrf2 activation and nuclear factor-kappaB (NF-κB) inhibition, respectively, both in vitro and in vivo. The results of this study indicate that X22 may be a promising cardioprotective agent and that Nrf2 and NF-κB may be important therapeutic targets for obesity-related complications.

  • Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and Imidazopyridine Derivatives
    2013
    Co-Authors: Gaozhi Chen, Zhiguo Liu, Xiaoou Shan, Lili Jiang, Yunjie Zhao, Zhiguo Feng, Shulin Yang, Yali Zhang, Guang Liang
    Abstract:

    Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and Imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the Imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new Imidazopyridines with potential therapeutic effects in acute inflammatory diseases

  • Synthesis and Anti-inflammatory Evaluation of Novel Benzimidazole and Imidazopyridine Derivatives
    ACS Medicinal Chemistry Letters, 2012
    Co-Authors: Gaozhi Chen, Zhiguo Liu, Zhang Yali, Xiaoou Shan, Lili Jiang, Yunjie Zhao, Zhiguo Feng, Shulin Yang, Guang Liang
    Abstract:

    Sepsis, an acute inflammatory disease, remains the most common cause of death in intensive care units. A series of benzimidazole and Imidazopyridine derivatives were synthesized and screened for anti-inflammatory activities, and the Imidazopyridine series showed excellent inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Compounds X10, X12, X13, X14, and X15 inhibited TNF-α and IL-6 release in a dose-dependent manner, and X12 showed no cytotoxicity in hepatic cells. Furthermore, X12 exhibited a significant protection against LPS-induced septic death in mouse models. Together, these data present a series of new Imidazopyridines with potential therapeutic effects in acute inflammatory diseases.

Susmita Mondal - One of the best experts on this subject based on the ideXlab platform.