Lopinavir

Side effects, interactions, and contraindications have only been evaluated in the drug combination lopinavir/ritonavir. They include nausea, vomiting, and stomach aches. ==Pharmacology==

Lopinavir is highly bound to plasma proteins (98–99%). Reports are contradictory regarding lopinavir penetration into the cerebrospinal fluid (CSF). Anecdotal reports state that lopinavir cannot be detected in the CSF; however, a study of paired CSF-plasma samples from 26 patients receiving lopinavir/ritonavir found lopinavir CSF levels above the IC50 in 77% of samples. ==Research==

A 2014 study indicates that lopinavir is effective against the human papilloma virus (HPV). The study used the equivalent of one tablet twice a day applied topically to the cervices of women with high-grade and low-grade precancerous conditions. After three months of treatment, 82.6% of the women who had high-grade disease had normal cervical conditions, confirmed by smears and biopsies. Lopinavir has been shown to impair protein synthesis via AMP-activated protein kinase (AMPK) and eEF2 kinase (eEF2K) activation, a mechanism that is similar to the antiviral effect of protein phosphatase 1 inhibitors. Lopinavir was found to inhibit MERS-CoV replication in the low-micromolar range in cell cultures. In 2020, lopinavir/ritonavir was found not to work in severe COVID-19. In this trial the medication was started typically around 13 days after the start of symptoms. ==Synthesis==

A couple of Lopinavir syntheses were reported: Below is one of them. L-Valine [72-18-4] (1) gives N-Phenoxycarbonyl-L-valine [126147-70-4] ('2). Treatment with 3-Chloropropylamine [14753-26-5] (3) gives (S)-3-methyl-2-(2-oxotetrahydropyrimidine-1-yl)butyric acid [192725-50-1] (4). Halogenation with thionyl chloride leads to (2S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoyl chloride [192800-77-4] (5). Reaction with (2S,3S,5S)-5-Amino-2-dibenzylamino-1,6-diphenyl-3-hydroxyhexane, PC9890651 (6) yields (S)-N-[(2S,4S,5S)-5-(Dibenzylamino)-4-hydroxy-1,6-diphenylhexan-2-YL]-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-YL)butanamide [192726-04-8] (7). The catalytic hydrogenation removes the protecting group to give (2S)-N-[(2S,4S,5S)-5-amino-4-hydroxy-1,6-diphenylhexan-2-yl]-3-methyl-2-(2-oxo-1,3-diazinan-1-yl)butanamide [192726-05-9] (8). Amide formation with (2,6-Dimethylphenoxy)acetyl Chloride [20143-48-0] (9) completes the synthesis of lopinavir (10). == References ==