title: Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group.
abstract: A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bungard
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Williams
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Jeanine E
authors.initials: JE
authors.lastname: Ballard
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bennett
authors.affiliation: Merck Frosst Centre for Therapeutic Research , 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Beaulieu
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bahnck-Teets
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Steve S
authors.initials: SS
authors.lastname: Carroll
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Chang
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: David C
authors.initials: DC
authors.lastname: Dubost
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: John F
authors.initials: JF
authors.lastname: Fay
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Diamond
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Greshock
authors.affiliation: Albany Molecular Research Singapore Research Center , 61 Science Park Road #05-01, The Galen Singapore Science Park II, Singapore 117525.
authors.forename: Li
authors.initials: L
authors.lastname: Hao
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: M Katharine
authors.initials: MK
authors.lastname: Holloway
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Felock
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Gesell
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Hua-Poo
authors.initials: HP
authors.lastname: Su
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Manikowski
authors.affiliation: Merck Frosst Centre for Therapeutic Research , 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McKay
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Mike
authors.initials: M
authors.lastname: Miller
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Xu
authors.initials: X
authors.lastname: Min
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Carmela
authors.initials: C
authors.lastname: Molinaro
authors.affiliation: Merck Frosst Centre for Therapeutic Research , 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Moradei
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Philippe G
authors.initials: PG
authors.lastname: Nantermet
authors.affiliation: Merck Frosst Centre for Therapeutic Research , 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Nadeau
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Rosa I
authors.initials: RI
authors.lastname: Sanchez
authors.affiliation: Albany Molecular Research Singapore Research Center , 61 Science Park Road #05-01, The Galen Singapore Science Park II, Singapore 117525.
authors.forename: Tummanapalli
authors.initials: T
authors.lastname: Satyanarayana
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: William D
authors.initials: WD
authors.lastname: Shipe
authors.affiliation: Albany Molecular Research Singapore Research Center , 61 Science Park Road #05-01, The Galen Singapore Science Park II, Singapore 117525.
authors.forename: Sanjay K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Merck Frosst Centre for Therapeutic Research , 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
authors.forename: Vouy Linh
authors.initials: VL
authors.lastname: Truong
authors.affiliation: Albany Molecular Research Singapore Research Center , 61 Science Park Road #05-01, The Galen Singapore Science Park II, Singapore 117525.
authors.forename: Sivalenka
authors.initials: S
authors.lastname: Vijayasaradhi
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Wiscount
authors.affiliation: Merck Frosst Centre for Therapeutic Research , 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacca
authors.affiliation: Merck Frosst Centre for Therapeutic Research , 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
authors.forename: Sheldon N
authors.initials: SN
authors.lastname: Crane
authors.affiliation: Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: McCauley
keywords: HIV; MK-8718; inhibitor; protease