title: Synthesis, antiviral activity and pharmacokinetics of P1/P1' substituted 3-aminoindazole cyclic urea HIV protease inhibitors.
abstract: A series of P1/P1' substituted cyclic urea analogues were prepared in an attempt to increase the intra-cellular antiviral potency of the nonsymmetrical 3-aminoindazoles DMP 850 and DMP 851. The effect of alkyl substitution of the P1/P1' residues on cellular antiviral potency, protein binding, resistance profile and pharmacokinetics are described.
authors.affiliation: Bristol-Myers Squibb Company, Experimental Station, Wilmington, DE 19880, USA. robert.kaltenbach@bms.com
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kaltenbach
authors.forename: Mona
authors.initials: M
authors.lastname: Patel
authors.forename: Robert E
authors.initials: RE
authors.lastname: Waltermire
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Harris
authors.forename: Benjamin R P
authors.initials: BR
authors.lastname: Stone
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Klabe
authors.forename: Sena
authors.initials: S
authors.lastname: Garber
authors.forename: Lee T
authors.initials: LT
authors.lastname: Bacheler
authors.forename: Beverly C
authors.initials: BC
authors.lastname: Cordova
authors.forename: Kelly
authors.initials: K
authors.lastname: Logue
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Wright
authors.forename: Susan
authors.initials: S
authors.lastname: Erickson-Viitanen
authors.forename: George L
authors.initials: GL
authors.lastname: Trainor
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004351:Drug Resistance; D006678:HIV / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives*
chemical_list: C116353:DMP 850; C116354:DMP 851; D017320:HIV Protease Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D014508:Urea