Design, synthesis and evaluations of spiro‐fused benzoxaborin derivatives as novel boron‐containing compounds

Abstract

Drug design using boron‐containing heterocycles has attracted a great deal of attention because these compounds are believed to possess high biological activity. However, information on the synthetic methodology and pharmacokinetic profiling of boron‐containing compounds is limited. In this study, we provide a new synthetic route for preparation of spiro‐fused benzoxaborin derivatives and investigate their in vitro pharmacokinetic properties. Our efforts led to the successful construction of a chemical library of spiro‐fused benzoxaborin derivatives with appropriate physicochemical and in vitro pharmacokinetic properties for oral drugs. These results indicate that the synthesized boron‐containing compounds are therefore eligible for classification in a novel chemical library.

Design, synthesis, pharmacological evaluation, and in silico studies of the activity of novel spiro pyrrolo[3,4-d]pyrimidine derivatives

“…N-((1-(Benzoylcarbamothioyl)cyclohexyl)carbamothioyl)benzamide (2). A mixture of cyclohexyl amine (0.025 mol) and benzoyl isothiocyanate (0.025 mol) in dioxane (15 mL) was heated under reux for 30 min., then stirred for 12 hours and the formed precipitate was ltered off, dried, and recrystallized from dilute ethanol to give compound 3 as a yellowish white powder.…”

“…1 The spiro heterocyclic structure is a distinguishing property of various natural and synthetic compounds with extraordinary biological activity. [2][3][4] The potential application of spiro heterocycles in pharmaceutical chemistry has been widely reported due to their good pharmacological characteristics [5][6][7][8][9][10][11] and geochemistry. [12][13][14] In addition, they have different uses as photocurrent resources 15 and asymmetric catalysts.…”

Spirocyclic Scaffolds in Medicinal Chemistry

“…Natsutani et al could synthesize spiro-fused benzoxaborins 173 in a four/five step protocol (Figure 4). 106 One superior effect of boron is its vacant p-orbital, which can covalently bind to target proteins, for instance with a serine or threonine residue of the target protein. The synthesized spirocycles were evaluated regarding their lipophilicity and metabolic stability in human liver microsomes (HLMs).…”

Synthesis, crystal structure, DFT and molecular docking studies of N-acetyl-2,4-[diaryl-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4′-acetyl-2′-(acetylamino)-4′,9-dihydro-[1′,3′,4′]-thiadiazoles: A potential SARS-nCoV-2 Mpro (COVID-19) inhibitor

“…Spiro heterocyclic structure is a unique feature of a several natural and synthetic products that possess remarkable biological activities [ 1 , 2 ]. The potential use of spiro heterocycles in medicinal chemistry has been well documented owing to their prominent pharmacological properties [3] .…”