Cyclotriazadisulfonamide (CADA) compounds specifically down-modulate the expression of CD4 receptor in lymphocytes and monocytes/macrophages, the primary receptors utilized by HIV for infection of target cells. CADA thus inhibits the entry of HIV and HHV-7 [Vermeire et al., Virology. 302 (2002) 342-353]. The mechanism of action of CADA compounds is completely different from those of any anti-HIV drugs currently in clinical use. The CD4 down-modulating and antiviral potencies of more than 25 CADA analogs have been described [Vermeire et al., Mol. Pharmacol. 63 (2003) 203-210]. Structural modifications of CADA were made to increase potency, reduce cytotoxicity, and improve physical properties. Several head group analogs were synthesized with polar groups and good leaving groups (Figure 1). Some of these head groups may regenerate the double bond of CADA by elimination reactions, potentially producing water-soluble pro-drugs. IsoCADA (SA05), an isomer of CADA, was synthesized by cyclization of 1,5,7-triazabicyclo-[4.4.0]dec-5-ene (TBD). This structural modification may reveal a relationship between the symmetry of the molecule and its biological activity. Two new fluorine containing analogs were also synthesized by modifying the toluenesulfonamide side arms. The anti-HIV and CD4 down modulation activities of these new CADA analogs are summarized.