Figure 5.

Structure–activity relationships of BA derivatives against HIV. A: 1. Activity disappears after introduction of fluorine at the C-2 position, and the proton at the C-2 position may play a key role in anti-HIV activity. 2. 3-β configuration is better than 3-α configuration. 3. The position of the dimethyl substitution on the side chain greatly influences activity. 4.The activity of the C-3 ester group is replaced by the bioisostere amide. B: 1. The isopropenyl group at position C-19 may not be an active pharmacophore, but proper modification can improve the water solubility of the drug, and thereby improving the pharmacokinetic properties of the drug. 2. R₁ as a hydrogen bond donor is unfavorable to the activity. 3. Changing the C-30 allyl group has no obvious effect on drug activity. C: 1. C-3 acylation can inhibit HIV maturation and C-28 amidation can prevent HIV from integrating into cell membranes. 2. The atomic length of the side chain at position C-28 is extremely significant for improving the antiviral efficacy, and the side chain structure containing amide groups is very important for activity. 3. The free hydroxyl group of R₃ and the free carboxyl group at the end of R₂ are necessary for anti-HIV activity. 4. When X is a secondary amine ring such as piperidine, it can significantly improve metabolic stability.