Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Krishnaiah, Maddeboina; Jin, Cheng; Sreenu, D.; Subrahmanyam, Vura Bala; Rao, Kota Sudhakar; Son, Dohyun; Park, Hyun-Ju; Kim, Seung Won; Sheen, Yhun Yhong; Kim, Dae‐Kee

doi:10.1016/j.ejmech.2012.09.011

Cited by 21 publications

(1 citation statement)

References 22 publications

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“…Among the mimics of natural bioactive molecules, α-amino phosphonates are important owing to their vast applications in biochemistry. , As a result of continuous efforts in this area, utilization of α-amino phosphonates are expanding into many new channels. , Among all the biological applications of α-amino phosphonates, more importantly it exhibits wide range of potential activities against cancer, − tuberculosis, , HIV , and bacterial agents, etc. − Amino phosphonates have been used as mimics of peptides, enzyme inhibitors and also as therapeutic agents for many diseases. − Apart from biological applications of amino phosphonates, α-amino phosphonates are serving as synthons for the construction of many new chemical entities. − Amino phosphonates facilitate simple methods for the synthesis of highly functionalized indoles, isocoumarins and many other heterocycles. − …”

Section: Introductionmentioning

confidence: 99%

A Green Approach to the Synthesis of α-Amino Phosphonate in Water Medium: Carbene Insertion into the N–H Bond by Cu(I) Catalyst

2016

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Synthesis of amino phosphonates is more important owing to their significant applications in the biological systems. There are few methods already known in the literature to make these molecules; however, known methods have their own disadvantages. In this regard, synthesis of different kinds of amino phosphonates have been achieved via phosphonate substituted carbene insertion into the N-H bond of aniline catalyzed by readily available copper salt under mild reaction conditions in water. In order to find an efficient catalyst for carbene insertion reaction in neat water, a large number of transition metal catalysts were screened, and we found that the [Cu(CHCN)]ClO was the best catalyst under employed reaction conditions. Using this environmentally benign methodology (copper catalyzed reaction in water), a large number of biologically important amino phosphonates have been synthesized, isolated (37 examples), and characterized using standard analytical and spectroscopic techniques.

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Section: Introductionmentioning

confidence: 99%

A Green Approach to the Synthesis of α-Amino Phosphonate in Water Medium: Carbene Insertion into the N–H Bond by Cu(I) Catalyst

2016

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2‐Aminothiazoles

2018

Privileged Structures in Drug Discovery

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Synthesis of amide derivatives containing the imidazole moiety and evaluation of their anti‐cardiac fibrosis activity

Yang,

Guo,

Liu

et al. 2024

Archiv der Pharmazie

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Three series of N‐{[4‐([1,2,4]triazolo[1,5‐α]pyridin‐6‐yl)‐5‐(6‐methylpyridin‐2‐yl)‐1H‐imidazol‐2‐yl]methyl}acetamides (14a–d, 15a–n, and 16a–f) were synthesized and evaluated for activin receptor‐like kinase 5 (ALK5) inhibitory activities in an enzymatic assay. The target compounds showed high ALK5 inhibitory activity and selectivity. The half maximal inhibitory concentration (IC50) for phosphorylation of ALK5 of 16f (9.1 nM), the most potent compound, was 2.7 times that of the clinical candidate EW‐7197 (vactosertib) and 14 times that of the clinical candidate LY‐2157299. The selectivity index of 16f against p38α mitogen‐activated protein kinase was >109, which was much higher than that of positive controls (EW‐7197: >41, and LY‐2157299: 4). Furthermore, a molecular docking study provided the interaction modes between the target compounds and ALK5. Compounds 14c, 14d, and 16f effectively inhibited the protein expression of α‐smooth muscle actin (α‐SMA), collagen I, and tissue inhibitor of metalloproteinase 1 (TIMP‐1)/matrix metalloproteinase 13 (MMP‐13) in transforming growth factor‐β‐induced human umbilical vein endothelial cells. Compounds 14c and 16f showed especially high activity at low concentrations, which suggests that these compounds could inhibit myocardial cell fibrosis. Compounds 14c, 14d, and 16f are potential preclinical candidates for the treatment of cardiac fibrosis.

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Synthesis and biological evaluation of 2-benzylamino-4(5)-(6-methylpyridin-2-yl)-5(4)-([1,2,4]triazolo[1,5-a]-pyridin-6-yl)thiazoles as transforming growth factor-β type 1 receptor kinase inhibitors

Cited by 21 publications

References 22 publications

A Green Approach to the Synthesis of α-Amino Phosphonate in Water Medium: Carbene Insertion into the N–H Bond by Cu(I) Catalyst

A Green Approach to the Synthesis of α-Amino Phosphonate in Water Medium: Carbene Insertion into the N–H Bond by Cu(I) Catalyst

2‐Aminothiazoles

Synthesis of amide derivatives containing the imidazole moiety and evaluation of their anti‐cardiac fibrosis activity

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