ADMET Prediction of synthesized Heterocyclic derivatives to treat renal cancer

Abstract

A library of 121 potent, synthesized, and characterized compounds from different heterocyclic derivatives such as pyrimidine, phthalazine, benzothiazole, benzpyrazoline, indoline, benzimidazole, phthalazine, indole, quinoline, quinazoline were selected based on their anti-renal cancer activity. The Drug likeness, Bioactivity, Absorption, Distribution, Metabolism, Excretion, and Toxicity of all the screened compounds were predicted through Molinspiration, PreADMET, and Osiris software. After screening 121 compounds, 19 compounds showed drug-like properties and an absorption percentage better than the standard drug Sorafenib. These compounds were further assessed based on their distribution parameter and the compounds that showed plasma protein binding equal to or below 90% and blood-brain barrier penetration below 1.000 were selected, i.e., compounds 3, 23, 64, 65 were then further assessed for the toxicity. Osiris property explorer was used to predict drug relevance and toxicity of the synthesized compounds. Compounds 3 and 23 were non-toxic similar to the standard drug Sorafenib. Compounds 3 and 23 were found to be active as Kinase Inhibitors, with a bioactivity score of 0.2 and 0.6 compared to standard drug sorafenib, which scored 0.44. Therefore Compound 3 N-(4-fluoro-2-methoxyphenyl)-7-methyl-5,6,7,8tetrahydropyrido [4',3':4,5] thieno[2,3-d] pyrimidin-4-amine and compound 23 1-(4-fluorophenyl)-3methyl-N-phenyl-3a,7a-dihydro-1H-pyrazolo [3,4-d] pyrimidin-4-amine belonging to pyrimidine derivatives were considered as best and suggested to be taken further for preclinical and clinical trials. The pyrimidine derivatives with anti-renal cancer activity can serve as a scaffold for the design of renal cancer targeting agents and motivates the further development of effective and safer compounds.