title: Cyclic sulfamide HIV-1 protease inhibitors, with sidechains spanning from P2/P2' to P1/P1'.
abstract: Previous studies of HIV protease inhibitors have shown that it is possible to elongate the P1/P1' sidechains to reach the S3/S3' binding sites. By analogy, we expected that it would be possible to design inhibitors reaching between the S1/S1' and S2/S2' binding sites. Molecular modeling suggested that this could be achieved with appropriate ortho-substitution of the P2/P2' benzyl groups in our cyclic sulfamide inhibitors. Four different spacer groups were investigated. The compounds were smoothly prepared from tartaric acid in five steps and exhibit low to moderate activity, the most potent inhibitor possessing a Ki value of 0.53 microM.
authors.affiliation: Department of Medicinal Chemistry, Uppsala University, BMC, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ax
authors.forename: Wesley
authors.initials: W
authors.lastname: Schaal
authors.forename: Lotta
authors.initials: L
authors.lastname: Vrang
authors.forename: Bertil
authors.initials: B
authors.lastname: Samuelsson
authors.forename: Anders
authors.initials: A
authors.lastname: Hallberg
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
mesh_terms: D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D013451:Sulfonic Acids / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D017320:HIV Protease Inhibitors; D013451:Sulfonic Acids; C005741:sulfamic acid