Structure Modification of Ritonavir with Carbazole; Synthesis and Characterization

The core moiety of ritonavir (2S, 3S, 5S)-5-(tertbutyloxycarbonyl)amino-2-amino-3-hydroxy-1,6-diphenylhexane (7) on condensation with oxirane of carbazole (8) in isopropyl alcohol at reflux and deprotected with mineral acid gave compound 10. Coupling of compound 10 with carbamate amino acid (11a-15c) in the presence of EDAC.HCl and HOBt at room temperature gave ritonavir analogues containing carbazole (16a-20c) as a novel for the human immunodeficiency virus (HIV)-1. These compound were characterized by IR, 1 H NMR and Mass spectroscopic. INTRODUCTION: Ritonavir {(2S, 3S, 5S)-[N[N-[[N-methyl-N-[(2-isopropyl-4-thiazolyl)methyl] amino] carbonyl]-L-valinyl]amino]-2-[N[(5-thiazolyl)methoxycarbonyl]amino]-1,6diphenyl-3-hydroxyhexane} is a human immunodeficiency virus (HIV) 1 . Protease inhibitor is indicated for the treatment of acquired immunodeficiency syndrome (AIDS) 2 . Peptidomimetic inhibitor is based on hydroxyl ethylene dipeptide isosteres show great efficacy against HIV-PR. Ritonavir (Fig. 1) is practically insoluble in water and could potentially exhibit dissolution rate limited absorption.