Title of article
Optimization of small molecule agonists of the thrombopoietin (Tpo) receptor derived from a benzo[a]carbazole hit scaffold
Author/Authors
Thomas H. Marsilje، نويسنده , , Phil B. Alper، نويسنده , , Wenshuo Lu، نويسنده , , Daniel Mutnick، نويسنده , , Pierre-Yves Michellys، نويسنده , , Yun He، نويسنده , , Donald S. Karanewsky، نويسنده , , Donald Chow، نويسنده , , Andrea Gerken، نويسنده , , Jianmin Lao، نويسنده , , Minju Kim، نويسنده , , H. Martin Seidel، نويسنده , , Shin-Shay Tian، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2008
Pages
4
From page
5259
To page
5262
Abstract
The lead optimization of a novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported. The chemical instability of the dihydro-benzo[a]carbazole lead 2 was successfully addressed in the design and evaluation of compounds which also demonstrated improved potency compared to 2. Members of the scaffold have been identified which are full agonists that demonstrate cellular functional potency <50 nM. Analog 21 demonstrates equivalent efficacy in the human megakaryocyte differentiation (CFU-mega) assay compared to Eltrombopag™.
Keywords
TPO , Thrombopoietin , TPOR , cMpl , Hematopoietic growth factor , agonist
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2008
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
799994
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