Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 2. Rational design of naphtho[1,2-d]imidazole thrombopoietin mimics.
The invention of a new class of naphtho[1,2-d]imidazole thrombopoietin mimics based on a pharmacophore hypothesis for small-molecule thrombopoietic agonists is discussed. Parallel array synthesis and purification techniques allowed for the rapid exploration of structure-activity relationships within this class and for the improvement in TPO mimetic potencies and efficacies.
Duffy
Kevin J
KJ
Price
Alan T
AT
Delorme
Evelyne
E
Dillon
Susan B
SB
Duquenne
Celine
C
Erickson-Miller
Connie
C
Giampa
Leslie
L
Huang
Yifang
Y
Keenan
Richard M
RM
Lamb
Peter
P
Liu
Nannan
N
Miller
Stephen G
SG
Rosen
Jon
J
Shaw
Anthony N
AN
Smith
Heather
H
Wiggall
Kenneth J
KJ
Zhang
Lihua
L
Luengo
Juan I
JI
D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D017930:Genes, Reporter; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D013926:Thrombopoietin / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology
D018952:Antigens, CD34; D007093:Imidazoles; D013926:Thrombopoietin; D008156:Luciferases