The influence of phosphate group on the drug-making properties of drugs

Improve bioavailability

Anavir has strong antiviral activity and good drug resistance, and has strong inhibitory activity against HIV
.
However, annavir has high lipophilicity (solubility of 0.
04 mg·mL-1), which limits its bioavailability when administered as a crystalline solid.
The pharmaceutical preparation must contain a higher proportion of organic excipients.
To promote dissolution in the stomach
.
Therefore, a single dose of the drug is usually administered in a soft capsule formula and multiple tablets, which brings inconvenience to the patient's medication
.
After introducing the phosphate group into its structure, the water solubility and solid stability of fusanavir obtained are significantly improved.
After being made into calcium salt tablets, it can be quickly absorbed by gastrointestinal epithelial cells and converted Anavir, the dose of 2 tablets is equivalent to 8 soft capsules of Anavir, which improves the bioavailability, reduces the dosage, and reduces the burden of medication on patients
.

05

Improve fat solubility

Stavudine (logP=-0.
59) is a class of anti-HIV drugs with good selectivity.
The drug needs to be converted into monophosphate compounds under the action of adenosine kinase, and then undergo diphosphorylation and triphosphorylation to achieve anti-HIV drugs.
The pharmacological activity of the virus
.
However, stavudine and its phosphorylation products are relatively polar, and it is difficult to reach the site of action
.
In order to improve its fat solubility, drug researchers introduced phosphate groups in its structure, thereby greatly improving the fat solubility of the drug and the ability of the drug to penetrate cell membranes (logP=2.
15), and at the same time, it also improved Stav Determine the degree of phosphorylation and selectivity
.

to sum up

The introduction of phosphate groups on the basis of the original drug not only improves the selectivity of the drug and reduces its side effects, but also improves the solubility, provides a variety of routes of administration, and greatly enhances the drug-making properties of the drug
.
Therefore, when some simple pharmacological methods cannot improve the druggability of a drug, phosphorylation structure modification can be a way to improve the druggability of a drug
.

references

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