Molecular Pharmacology. The mode of action of biologically active compounds. vol. 1. E. J. Ariens, Ed. Academic Press, New York, 1964. xxii + 503 pp. Illus. $17

Science ◽  
1964 ◽  
Vol 145 (3633) ◽  
pp. 695-696
Author(s):  
L. J. Roth
2021 ◽  
Vol 16 ◽  
Author(s):  
Nelson José Freitas da Silveira ◽  
Walter Filgueira de Azevedo Jr. ◽  
Rita Cardoso Guedes ◽  
Leandro Marcos Santos ◽  
Rodolfo Cabral Marcelino ◽  
...  

Background: In the rational drug development field, a bioisosterism is a tool that improves lead compounds performance, reffering to molecular fragment substitution that has similar physical-chemical properties. Thus, it is possible to modulate drug properties such as absorption, toxicity, and half-life increase. This modulation is of pivotal importance in the discovery, development, identification, and interpretation of the mode of action of biologically active compounds. Objective: Our purpose here is to review the development and application of bioisosterism in drug discovery. In this study history, applications, and use of bioisosteric molecules to create new drugs with high binding affinity in the protein-ligand complexes are described. Method: It is an approach for molecular modification of a prototype based on the replacement of molecular fragments with similar physicochemical properties, being related to the pharmacokinetic and pharmacodynamic phase, aiming at the optimization of the molecules. Results: Discovery, development, identification, and interpretation of the mode of action of biologically active compounds are the most important factors for drug design. The strategy adopted for the improvement of leading compounds is bioisosterism. Conclusion: Bioisosterism methodology is a great advance for obtaining new analogs to existing drugs, enabling the development of new drugs with reduced toxicity, in a comparative analysis with existing drugs. Bioisosterism has a wide spectrum to assist in several research areas.


2018 ◽  
Author(s):  
Honggui Lv ◽  
Li-Jun Xiao ◽  
Dongbing Zhao ◽  
Qi-Lin Zhou

Herein, we realized the first linear-selective hydroarylation of unactivated alkenes and styrenes with organoboronic acids by introducing directing groupon alkenes. Our method is highly efficient and scalable, and provides a modular route to assemble structurally diverse alkylarenes, especially for γ-aryl butyric acid derivatives, which have been widely utilized as chemical feedstocks to access multiple marketed drugs, and biologically active compounds.<br>


2020 ◽  
Vol 5 (443) ◽  
pp. 85-91
Author(s):  
Ibrayev M.K., ◽  
◽  
Takibayeva A.T., ◽  
Fazylov S.D., ◽  
Rakhimberlinova Zh.B., ◽  
...  

This article presents studies on the targeted search for new derivatives of azoles, such as benzthiazole, 3,5-dimethylpyrazole, 1,3,4-oxadiazole-2-thione, 1,3,4-thiadiazole. The possibility of combining in one molecule of the azole ring with other cyclic compounds: the alkaloid cytisine, morpholine, furan and some arenes has been studied. To obtain new compounds, the reactions of bromination, acylation, and interaction with isothiocyanates were studied. Optimal synthesis conditions were studied for all reactions. It was found that the reaction of 4-bromo-3,5-dimethylpyrazole with isothiocyanates, in contrast to the previously written derivatives of anilines, takes a longer time and requires heating the reaction mixture. The combination of a pirasol fragment with halide substituents often results in an enhanced therapeutic effect. The synthesized 2-bromine-N-(6-rodanbenzo[d]thiazole-2-yl)acetamide, due to the alkylbromide group, is an important synth in the synthesis of new benzthiazole derivatives. Its derivatives combine in one molecule the rest of rhodanbenzthiazole with alkaloid cytisine and biogenic amine morpholine and are potentially biologically active compounds, since the molecule structure contains several pharmacophoric fragments: benzthiazole and alkaloid (amine) heterocycles, rhodane and urea groups. The mechanism of formation of 1,3,4-oxadiazole-2-tyons from hydrazides under action on them by carbon disulfide was studied and assumed. It was shown that dithiocarbamates in acidic medium decompose with the release of hydrogen sulfide and the formation of highly reactive isothiocyanate group. Then, intra-molecular cyclization occurs, with the formation of end products - 1,3,4-oxadiazole-2-thions. The structures of the synthesized compounds were studied by 1H and 13C NMR spectroscopy. All synthesized substances are potentially biologically active compounds, since they contain several pharmacophore fragments in their structure.


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