Design of a series of bicyclic HIV-1 integrase inhibitors. Part 1: selection of the scaffold.
HIV integrase inhibitors based on a novel bicyclic pyrimidinone core is presented. Nine variations of the core scaffold are evaluated leading to optimization of the 6:6 core giving compound 48 with an EC(50) of 3 nM against wild type HIV infected T-cells.
Jones
Eric D
ED
Avexa Ltd, 576 Swan Street, Richmond, Victoria 3121, Australia.
Vandegraaff
Nick
N
Le
Giang
G
Choi
Neil
N
Issa
William
W
Macfarlane
Katherine
K
Thienthong
Neeranat
N
Winfield
Lisa J
LJ
Coates
Jonathan A V
JA
Lu
Long
L
Li
Xinming
X
Feng
Xiao
X
Yu
Changjiang
C
Rhodes
David I
DI
Deadman
John J
JJ
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000821:virology
D001643:Bridged Bicyclo Compounds; D019428:HIV Integrase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1