title: Discovery of novel benzothiazolesulfonamides as potent inhibitors of HIV-1 protease.
abstract: The human immunodeficiency virus (HIV) has been shown to be the causative agent for AIDS. The HIV virus encodes for a unique aspartyl protease that is essential for the production of enzymes and proteins in the final stages of maturation. Protease inhibitors have been useful in combating the disease. The inhibitors incorporate a variety of isosteres including the hydroxyethylurea at the protease cleavage site. We have shown that the replacement of t-butylurea moiety by benzothiazolesulfonamide provided inhibitors with improved potency and antiviral activities. Some of the compounds have shown good oral bioavailability and half-life in rats. The synthesis of benzothiazole derivatives led us to explore other heterocycles. During the course of our studies, we also developed an efficient synthesis of benzothiazole-6-sulfonic acid via a two-step procedure starting from sulfanilamide.
authors.affiliation: Pfizer Global Research and Development, Pfizer Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA. srinivasan.nagarajan@pfizer.com
authors.forename: Srinivasan R
authors.initials: SR
authors.lastname: Nagarajan
authors.forename: Gary A
authors.initials: GA
authors.lastname: De Crescenzo
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Getman
authors.forename: Hwang Fun
authors.initials: HF
authors.lastname: Lu
authors.forename: James A
authors.initials: JA
authors.lastname: Sikorski
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Walker
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: McDonald
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Houseman
authors.forename: Geralyn P
authors.initials: GP
authors.lastname: Kocan
authors.forename: Nandini
authors.initials: N
authors.lastname: Kishore
authors.forename: Pramod P
authors.initials: PP
authors.lastname: Mehta
authors.forename: Christie L
authors.initials: CL
authors.lastname: Funkes-Shippy
authors.forename: Lisa
authors.initials: L
authors.lastname: Blystone
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D013844:Thiazoles; D014508:Urea; C006865:butylurea; D016333:HIV Protease