Spiropiperidine CCR5 antagonists.
A novel series of CCR5 antagonists has been identified, utilizing leads from high-throughput screening which were further modified based on insights from competitor molecules. Lead optimization was pursued by balancing opposing trends of metabolic stability and potency. Selective and potent analogs with good pharmacokinetic properties were successfully developed.
Rotstein
David M
DM
Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. david.rotstein@roche.com
Gabriel
Stephen D
SD
Makra
Ferenc
F
Filonova
Lubov
L
Gleason
Shelley
S
Brotherton-Pleiss
Christine
C
Setti
Lina Q
LQ
Trejo-Martin
Alejandra
A
Lee
Eun Kyung
EK
Sankuratri
Surya
S
Ji
Changhua
C
Derosier
Andre
A
Dioszegi
Marianna
M
Heilek
Gabrielle
G
Jekle
Andreas
A
Berry
Pamela
P
Weller
Paul
P
Mau
Cheng-I
CI
D000818:Animals; D065100:CCR5 Receptor Antagonists; D018938:Caco-2 Cells; D004285:Dogs; D000882:Haplorhini; D006801:Humans; D010880:Piperidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D019713:Receptors, CCR5 / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
D065100:CCR5 Receptor Antagonists; D010880:Piperidines; D019713:Receptors, CCR5; D013141:Spiro Compounds