title: 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 3: polar functionality and its effect on anti-HIV-1 activity.
abstract: Incorporation of acidic functional groups into a lead CCR5 antagonist identified from a targeted combinatorial library resulted in compounds with enhanced anti-HIV-1 activity and attenuated L-type calcium channel affinity.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. jeffrey_hale@merck.com
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Hale
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Budhu
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Gould
authors.forename: Julie A
authors.initials: JA
authors.lastname: DeMartino
authors.forename: Martin S
authors.initials: MS
authors.lastname: Springer
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Siciliano
authors.forename: Lorraine
authors.initials: L
authors.lastname: Malkowitz
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Daria
authors.initials: D
authors.lastname: Hazuda
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.forename: Joseph
authors.initials: J
authors.lastname: Kessler
authors.forename: Renee
authors.initials: R
authors.lastname: Danzeisen
authors.forename: Karen
authors.initials: K
authors.lastname: Holmes
authors.forename: Janet
authors.initials: J
authors.lastname: Lineberger
authors.forename: Anthony
authors.initials: A
authors.lastname: Carella
authors.forename: Gwen
authors.initials: G
authors.lastname: Carver
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D020746:Calcium Channels, L-Type / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D054407:Chemokine CCL4; D006224:Cricetinae; D015497:HIV-1 / Q000187:drug effects*; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000037:antagonists & inhibitors; D051381:Rats; D019713:Receptors, CCR5 / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D020746:Calcium Channels, L-Type; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5