Which antihypertensive drug has tetrazole nucleus?

Some tetrazole-containing drugs such as losartan, valsartan, irbesartan and candesartan have already been used for the treatment of hypertension in clinical practice, demonstrating the potential of tetrazole derivatives as putative antihypertensive drugs [17].

What is tetrazole used for?

A well-known tetrazole is dimethyl thiazolyl diphenyl tetrazolium bromide (MTT). This tetrazole is used in the MTT assay to quantify the respiratory activity of live cells culture, although it generally kills the cells in the process. Some tetrazoles can also be used in DNA assays.

Which is the Bioisostere for carboxylic acid?

Although hydroxamic acids are most commonly employed in drug design for their metal-chelating properties, this functional group has also been employed successfully as a carboxylic acid bioisostere.

What are some potential problems in using Bioisosteric replacements for lead modification?

The replacement can attenuate toxicity, modify activity of lead, and/or alter pharmacokinetics or the toxicity of the lead.

Which is used for Bioisosteric replacement of benzene ring?

The replacement of para-substituted benzenes with saturated bi- and polycyclic bioisosteres – bicyclo[1.1. 1]pentane, bicyclo[2.2. 2]octane and cubane, – often increases the potency, selectivity and metabolic stability of bioactive compounds.

Is tetrazole acidic or basic?

The acidic nature of tetrazole is similar to corresponding carboxylic acids, but there is a difference in annular tautomerism of ring tetrazoles to carboxylic acids. The acidic nature of tetrazole is mainly affected by substitution compound nature at C-5 position.

Is tetrazole soluble in water?

Lower tetrazoles, RCN4H, like lower carboxylic acids, RCO2H, are highly soluble in water and cannot be easily crystalized from it. Lower tetrazoles are best crystallized from solvents such as ethyl acetate or toluene–pentane mixtures.

What does Isosteres mean?

From Wikipedia, the free encyclopedia. Classical Isosteres are molecules or ions with similar shape and often electronic properties. Many definitions are available. but the term is usually employed in the context of bioactivity and drug development.

What is the difference between Isosteres and Bioisosteres?

Friedman (1951): Bioisosteres are atoms or molecules that fit the broadest definition for isosteres and have the same type of biological activity. Thornber (1979): Groups or molecules which have chemical and physical similarities producing broadly similar biological effects.

Is used for Bioisosteric replacement of benzene?

1]pentane were validated as saturated bioisosteres for para-substituted benzenes in medicinal chemistry projects. It was shown that such replacement increases the water solubility, lowers lipophilicity and retains bioactivity of compounds.

How are tetrazole and carboxylic acid bioisosteres alike?

The carboxylic acid and tetrazole bioisosteric pairs exhibit very similar H-bond environments in crystal structures from the CSD, and the attractive energies of these H-bonds are very similar. However, the H-bond environments around 1H-tetrazole and tetrazolate substituents extend further away, by ≈1.2 Å, from the core of the connected molecule.

How does tetrabenazine work as a bioisosteric replacement?

Tetrabenazine acts primarily as a reversible high-affinity inhibitor of mono-amine uptake into granular vesicles of presynaptic neurons by binding selectively to VMAT-2. Whilst Tetrabenazine is well absorbed it has relatively low bioavailability DOI and the primary route for metabolism is via oxidation by CYP2D6.

Which is the best heterocycle replacement for phenyl tetrazole?

Heterocycle replacements attempted for the phenyl tetrazole ( 86 Rb + efflux % inhibition at 30 μM). 31 With the modified scaffold and a new nitrophenyl bioisostere in hand we again paired these features with the other available isosteres and further probed SAR, providing the compounds described in Table 4.

Which is better 1 hydroxypyrazole or tetrazole?

One advantage of the 1-hydroxypyrazole derivatives in comparison to the carboxylic acid and tetrazole is the higher pKa values, which can lead to more efficient tissue permeation.