Syntheses and anti-HIV and human cluster of differentiation 4 (CD4) down-modulating potencies of pyridine-fused cyclotriazadisulfonamide (CADA) compounds.

摘要: CADA compounds selectively down-modulate human cell-surface CD4 protein and are of interest as HIV entry inhibitors drugs for asthma, rheumatoid arthritis, diabetes some cancers. Postulating that fusing a pyridine ring bearing hydrophobic substituents into the macrocyclic scaffold may lead to potent with improved properties, 17 macrocycles were synthesized, 14 12-membered rings having an isobutylene head group, two arenesulfonyl side arms, fused para substituent. The analogs display wide range down-modulating anti-HIV potencies, including greater potency than CADA, proving highly basic nitrogen atom in is not required enhance pyridine-fused compounds. Cytotoxicities new compared favorably those showing incorporation can produce selective potently proteins medicinal interest.