The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TPO activity, particularly diseases or disorders that involve thrombocytopenia.
Optimization of small molecule agonists of the thrombopoietin (Tpo) receptor derived from a benzo[a]carbazole hit scaffold
作者:Thomas H. Marsilje、Phil B. Alper、Wenshuo Lu、Daniel Mutnick、Pierre-Yves Michellys、Yun He、Donald S. Karanewsky、Donald Chow、Andrea Gerken、Jianmin Lao、Min-Ju Kim、H. Martin Seidel、Shin-Shay Tian
DOI:10.1016/j.bmcl.2008.08.077
日期:2008.10
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(TM). (C) 2008 Elsevier Ltd. All rights reserved.
HETEROTETRACYCLIC COMPOUNDS AS TPO MIMETICS
申请人:IRM, LLC
公开号:EP1910338A2
公开(公告)日:2008-04-16
US8153671B2
申请人:——
公开号:US8153671B2
公开(公告)日:2012-04-10
[EN] COMPOUNDS AND COMPOSITIONS AS TPO MIMETICS<br/>[FR] COMPOSES ET COMPOSITIONS UTILISES COMME MIMETIQUES DE LA TPO
申请人:IRM LLC
公开号:WO2007009120A2
公开(公告)日:2007-01-18
[EN] The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or deregulated TPO activity, particularly diseases or disorders that involve thrombocytopenia. [FR] La présente invention concerne une nouvelle classe de composés, des compositions pharmaceutiques comprenant ces composés et des procédés d'utilisation de tels composés pour traiter ou prévenir des maladies ou des troubles associés à une activité anormale ou déréglée de la thrombopoïétine (TPO), en particulier des maladies ou des troubles impliquant la thrombocytopénie.