Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2<i>H</i>-benzo[<i>f</i>]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes

Li, Shiliang; Xu, Hao; Cui, Shichao; Wu, Fangshu; Zhang, Youli; Su, Mingbo; Gong, Ying-hui; Qiu, Shaobing; Jiao, Qian; Qin, Chun; Shan, Jiwei; Zhang, Ming; Wang, Jiawei; Qiao, Yin; Xu, Minghao; Liu, Xiaofeng; Wang, Rui; Zhu, Lili; Li, Jia; Xu, Yufang; Jiang, Hualiang; Zhao, Zhenjiang; Li, Honglin

doi:10.1021/acs.jmedchem.6b00505

Cited by 52 publications

(50 citation statements)

References 61 publications

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“…Hao et al discovered two series of potent and selective EGFR inhibitors againstL858R/T790 M resistance mutation by scaffold hopping with SHAFTS . Li et al discovered and designed a series of novel and potent DPP‐4 inhibitors for treating type 2 diabetes mellitus (T2DM) based on a natural product lead using SHAFTS . Wang et al used SHAFTS method for scaffold hopping and discovered a potent inhibitor of human copper trafficking for the treatment of cancer …”

Section: Experiments and Discussionmentioning

confidence: 99%

eSHAFTS: Integrated and graphical drug design software based on 3D molecular similarity

Song

Wei

et al. 2019

J Comput Chem

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With the development of computer technology, computer‐aided drug design (CADD) has become an important means for drug research and development, and its representative method is virtual screening. Various virtual screening platforms have emerged in an endless stream and play great roles in the field of drug discovery. With the increasing number of compound molecules, virtual screening platforms face two challenges: low fluency and low visibility of software operations. In this article, we present an integrated and graphical drug design software eSHAFTS based on three‐dimensional (3D) molecular similarity to overcome these shortcomings. Compared with other software, eSHAFTS has four main advantages, which are integrated molecular editing and drawing, interactive loading and analysis of proteins, multithread and multimode 3D molecular similarity calculation, and multidimensional information visualization. Experiments have verified its convenience, usability, and reliability. By using eSHAFTS, various tasks can be submitted and visualized in one desktop software without locally installing any dependent plug‐ins or software. The software installation package can be downloaded for free at http://lilab.ecust.edu.cn/home/resource.html. © 2019 Wiley Periodicals, Inc.

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Section: Experiments and Discussionmentioning

confidence: 99%

eSHAFTS: Integrated and graphical drug design software based on 3D molecular similarity

Song

Wei

et al. 2019

J Comput Chem

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“…From the comparison of DPP-4 level between child patients and normal children, it was found that DPP-4 level of child patients with T1DM significantly increased, according to the feature of insulin absolute shortage for T1DM. In addition, after the treatment with insulin, the DPP-4 level of children with T1DM decreased obviously, so we speculated that it may depend on the function characteristics of DPP-4, which mainly included (18–20): i) The function of regulating pancreas β cells and secrete insulin; ii) the unique insulin dependence feature of secreting and regulating blood glucose when glucose is increasing in human body. Therefore, it has a defensive function for pancreas β cells, which can significantly reduce the apoptosis of pancreas β cells and prolong the life span of islet cells (8).…”

Section: Discussionmentioning

confidence: 99%

Influence of nutritional intervention on children with type 1 diabetes mellitus and DPP-4 in serum

Dong

Liu

Chen

et al. 2017

Experimental and Therapeutic Medicine

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The level of dipeptidyl peptidase-4 (DPP-4) of children with type 1 diabetes mellitus (T1DM) was observed to evaluate the improvement in function of the nutritional intervention. In total, 132 children with T1DM (T1DM group) and 132 healthy children (NC group) based on physical examination admitted to our hospital from September 2014 to June 2015 and were studied. General data of the two groups as well as the concentration of DPP-4 and various biochemical criterion in peripheral serum were collected and analyzed. Compared with NC group, DPP-4 level of T1DM group was obviously increased (P<0.05); after insulin treatment, the serum level of DPP-4 of T1DM group decreased, but was still significantly higher than that of NC group (P<0.05). After 3 months of clinical nutritional intervention, body mass index (BMI) of children with T1DM was significantly reduced compared with data before the treatment (P<0.05). However, the level of DPP-4 appeared unchanged (P>0.05). Pearson's correlation analysis showed that the level of DPP-4 had a positive correlation with diabetic duration, BMI and gamma (γ)-glutamyl transpeptidase for children suffering TIDM (P<0.05). Multiple linear regression analysis showed that BMI may be a factor influencing DPP-4 level in serum of T1DM children. In conclusion, the level of DPP-4 in serum increased, and insulin treatment was able to decrease DPP-4 level in T1DM children. However, clinical nutritional intervention could not improve the level of DPP-4 and BMI may be an influental factor of the DPP-4 level.

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“…4 Given the clinical success of DPP-4 inhibitors, there has been ongoing interest in the development of drug candidates with longer half-lives that decrease dosing frequency. 5 Such therapies would provide advantages to the patient of improved medication compliance and minimized side effects. In this vein, omarigliptin ( 1 , MK-3102), a highly functionalized long-acting DPP-4 inhibitor, was developed and recently approved for the once-weekly treatment of type 2 diabetes in Japan (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin

Peng¹,

Chen²,

Chen³

et al. 2017

J. Org. Chem.

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A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting-group- and precious-metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael–lactolization–dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade. The synthesis of this complex intermediate utilizes simple starting materials and proceeds in four linear steps.

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Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes

Cited by 52 publications

References 61 publications

eSHAFTS: Integrated and graphical drug design software based on 3D molecular similarity

eSHAFTS: Integrated and graphical drug design software based on 3D molecular similarity

Influence of nutritional intervention on children with type 1 diabetes mellitus and DPP-4 in serum

Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin

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