3D QSAR studies of 1,3,4-benzotriazepine derivatives as CCK2 receptor antagonists

Κaur, Kirandeep; Talele, Tanaji T.

doi:10.1016/j.jmgm.2008.07.003

Cited by 16 publications

(9 citation statements)

References 57 publications

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“…Evaluation of the relationship between structure and biological activity of compounds by PLS method can quantitate the reliability of the model [32]. The analysis was divided into two parts, the training set database were cross-validated by using the leave-one-out method to calculate the cross-validation correlation coe cient (Q 2 ) and the optimum number of components (ONC) [33]. Then, the non-crossvalidation correlation coe cient (R 2 ), Fisher's test value (F value) and the standard error of estimate (SEE) were calculated through non-cross-validation analysis [34].…”

Section: Partial Least Squares (Pls) Analysismentioning

confidence: 99%

Computational investigation of adenosine 5′-(α,β-methylene)-diphosphate (AMPCP) derivatives as ecto-5′-nucleotidase (CD73) inhibitors by using 3D-QSAR, molecular docking, and molecular dynamics simulations

et al. 2022

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CD73, as a surface enzyme anchored on the outside of the cell membrane via glycosylphosphatidylinositol (GPI), can convert the AMP in the tumor cell microenvironment into adenosine to promote the growth of tumor cells. It has been overexpressed in many different types of human tumors, such as gastric cancer, pancreatic cancer, liver cancer and other tumor cells. Therefore, targeted inhibitors of CD73 are considered as potential tumor treatment methods. Due to the low bioavailability of nucleoside CD73 inhibitors, it is necessary to develop new inhibitors. In this study, through molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular dynamics (MD) simulations, a series of CD73 inhibitors were calculated and studied to reveal their structure-activity relationships. Through molecular docking studies, explore the possible mode of interaction between inhibitors and protein. Subsequently, a 3D-QSAR model was established by comparative molecular eld analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). For the best CoMFA model, the Q 2 and R 2 values are 0.708 and 0.983, respectively, while for the best CoMSIA model, the Q 2 and R 2 values are 0.809 and 0.992, respectively. In addition, the stability of the complex formed by the two inhibitors and CD73 was evaluated by molecular dynamics simulation, and the results are consistent with the results of molecular docking and 3D-QSAR research. Finally, the binding free energy was calculated by the surface area method (MM-GBSA), and the results are consistent with the activities that Van Der Waals and Coulomb contribute the most during the binding process of the molecule to the CD73 protein. In conclusion, our research provides valuable information for the further development of CD73 inhibitors.

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Section: Partial Least Squares (Pls) Analysismentioning

confidence: 99%

Computational investigation of adenosine 5′-(α,β-methylene)-diphosphate (AMPCP) derivatives as ecto-5′-nucleotidase (CD73) inhibitors by using 3D-QSAR, molecular docking, and molecular dynamics simulations

et al. 2022

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“…They are of great interest because of their diverse pharmacological properties. For example, 1,2,4-triazepin-3-ones/thiones are effective antagonists of parathyroid hormone 1 (PTH1R) [7] and holecystokinin hormone 2 (CCK2) [8,9] receptors. Some of them possess antioxidant [10], antipsychotic [11,12], and HIV protease inhibitory activities [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

A General Stereoselective Approach to 1,2,4-Triazepane-3-thiones/ones via Reduction or Reductive Alkylation of 2,4,5,6-Tetrahydro-3H-1,2,4-triazepine-3-thiones/ones

Fesenko

Шуталев

2018

22nd International Electronic Conference on Synthetic Organic Chemistry

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A general stereoselective approach to previously unknown 1,2,4-triazepane-3-thiones/ones based on reduction or reductive alkylation of readily available 2,4,5,6-tetrahydro-3H-1,2,4-triazepine- 3-thiones/ones has been developed. The approach involved treatment of tetrahydrotriazepines with sodium cyanoborohydride in MeOH at pH 3 or with sodium borohydride and excess of carboxylic acid in tetrahydrofuran to give 1-unsubstituted or 1-alkyl-substituted 1,2,4-triazepane-3- thiones/ones, respectively. The latter were also prepared by reaction of 1-unsubstituted 1,2,4- triazepane-3-thiones/ones with sodium cyanoborohydride and aldehyde in MeOH in the presence of AcOH.

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“…On the other hand, some 1,3,4-benzotriazepine derivatives, such as 5 , were found to be suitable as a nonpeptide parathyroid hormone-1 receptor (PTH1R) antagonist . Recent 3D QSAR studies of various 1,3,4-benzotriazepine derivatives showed their activity as a cholecystokinin (CCK 2 ) receptor antagonist …”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of Pyrrolotriazepine Derivatives: An Experimental and Computational Study

et al. 2013

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The pyrrole derivatives having carbonyl groups at the C-2 position were converted to N-propargyl pyrroles. The reaction of those compounds with hydrazine monohydrate resulted in the formation of 5H-pyrrolo[2,1-d][1,2,5]triazepine derivatives. The synthesis of these compounds was accomplished in three steps starting from pyrrole. On the other hand, attempted cyclization of a pyrrole ester substituted with a propargyl group at the nitrogen atom gave, unexpectedly, the six-membered cyclization product, 2-amino-3-methylpyrrolo[1,2-a]pyrazin-1(2H)-one as the major product. The expected cyclization product with a seven-membered ring, 4-methyl-2,3-dihydro-1H-pyrrolo[2,1-d][1,2,5]triazepin-1-one was formed as the minor product and was converted quantitatively to the major product. The formation mechanism of the products was investigated, and the results obtained were also supported by theoretical calculations.

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3D QSAR studies of 1,3,4-benzotriazepine derivatives as CCK2 receptor antagonists

Cited by 16 publications

References 57 publications

Computational investigation of adenosine 5′-(α,β-methylene)-diphosphate (AMPCP) derivatives as ecto-5′-nucleotidase (CD73) inhibitors by using 3D-QSAR, molecular docking, and molecular dynamics simulations

Computational investigation of adenosine 5′-(α,β-methylene)-diphosphate (AMPCP) derivatives as ecto-5′-nucleotidase (CD73) inhibitors by using 3D-QSAR, molecular docking, and molecular dynamics simulations

A General Stereoselective Approach to 1,2,4-Triazepane-3-thiones/ones via Reduction or Reductive Alkylation of 2,4,5,6-Tetrahydro-3H-1,2,4-triazepine-3-thiones/ones

Design and Synthesis of Pyrrolotriazepine Derivatives: An Experimental and Computational Study

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