Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 2. Rational design of naphtho[1,2-d]imidazole thrombopoietin mimics

Kevin J Duffy; Alan T Price; Evelyne Delorme; Susan B Dillon; Celine Duquenne; Connie Erickson-Miller; Leslie Giampa; Yifang Huang; Richard M Keenan; Peter Lamb; Nannan Liu; Stephen G Miller; Jon Rosen; Anthony N Shaw; Heather Smith; Kenneth J Wiggall; Lihua Zhang; Juan I Luengo

doi:10.1021/jm0255365

Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 2. Rational design of naphtho[1,2-d]imidazole thrombopoietin mimics

J Med Chem. 2002 Aug 15;45(17):3576-8. doi: 10.1021/jm0255365.

Authors

Kevin J Duffy, Alan T Price, Evelyne Delorme, Susan B Dillon, Celine Duquenne, Connie Erickson-Miller, Leslie Giampa, Yifang Huang, Richard M Keenan, Peter Lamb, Nannan Liu, Stephen G Miller, Jon Rosen, Anthony N Shaw, Heather Smith, Kenneth J Wiggall, Lihua Zhang, Juan I Luengo

PMID: 12166929
DOI: 10.1021/jm0255365

Abstract

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.

MeSH terms

Antigens, CD34 / metabolism
Bone Marrow Cells / drug effects
Bone Marrow Cells / metabolism
Cell Differentiation
Cell Division / drug effects
Cell Line
Combinatorial Chemistry Techniques
Genes, Reporter
Humans
Imidazoles / chemical synthesis*
Imidazoles / chemistry
Imidazoles / pharmacology
Luciferases / genetics
Luciferases / metabolism
Models, Molecular
Molecular Mimicry
Phosphorylation
Structure-Activity Relationship
Thrombopoietin / chemistry*
Thrombopoietin / genetics
Thrombopoietin / pharmacology

Substances

Antigens, CD34
Imidazoles
Thrombopoietin
Luciferases