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

被引：46

作者：

Duffy, KJ

Price, AT

Delorme, E

Dillon, SB

Duquenne, C

Erickson-Miller, C

Giampa, L

Huang, YF

Keenan, RM

Lamb, P

Liu, NN

Miller, SG

Rosen, J

Shaw, AN

Smith, H

Wiggall, KJ

Zhang, LH

Luengo, JI

机构：

[1] GlaxoSmithKline, Collegeville, PA 19426 USA

[2] Ligand Pharmaceut Inc, San Diego, CA 92121 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 17期

关键词：

D O I：

10.1021/jm0255365

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：3576 / 3578

页数：3

共 8 条

[1]

*CHEM COMP GROUP I, 1997, MOE 2001 01

[2] Identification of a pharmacophore for thrombopoietic activity of small, non-peptidyl molecules. 1. Discovery and optimization of salicylaldehyde thiosemicarbazone thrombopoietin mimics [J].

Duffy, KJ ;

Shaw, AN ;

Delorme, E ;

Dillon, SB ;

Erickson-Miller, C ;

Giampa, L ;

Huang, YF ;

Keenan, RM ;

Lamb, P ;

Liu, NN ;

Miller, SG ;

Price, AT ;

Rosen, J ;

Smith, H ;

Wiggall, KJ ;

Zhang, LH ;

Luengo, JI .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (17) :3573-3575

[3] Hydrazinonaphthalene and azonaphthalene thrombopoietin mimics are nonpeptidyl promoters of megakaryocytopoiesis [J].

Duffy, KJ ;

Darcy, MG ;

Delorme, E ;

Dillon, SB ;

Eppley, DF ;

Erickson-Miller, C ;

Giampa, L ;

Hopson, CB ;

Huang, YF ;

Keenan, RM ;

Lamb, P ;

Leong, L ;

Liu, NN ;

Miller, SG ;

Price, AT ;

Rosen, J ;

Shah, R ;

Shaw, TN ;

Smith, H ;

Stark, KC ;

Tian, SS ;

Tyree, C ;

Wiggall, KJ ;

Zhang, L ;

Luengo, JI .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (22) :3730-3745

[4]

DUFFY KJ, UNPUB

[5] Establishment and characterization of the thrombopoietin-dependent megakaryocytic cell line, UT-7/TPO [J].

Komatsu, N ;

Kunitama, M ;

Yamada, M ;

Hagiwara, T ;

Kato, T ;

Miyazaki, H ;

Eguchi, M ;

Yamamoto, M ;

Miura, Y .

BLOOD, 1996, 87 (11) :4552-4560

[6] Drug discovery using receptors that modulate gene expression [J].

Lamb, P ;

Rosen, J .

JOURNAL OF RECEPTOR AND SIGNAL TRANSDUCTION RESEARCH, 1997, 17 (1-3) :531-543

[7]

PRICE AC, UNPUB

[8]

TAKEBE Y, 1989, MED IMMUNOL, V18, P425

← 1 →