SAR study of 2,3,4,14b-tetrahydro-1H-dibenzo[b,f]pyrido[1,2-d][1,4]oxazepines as progesterone receptor agonists

We have developed a new class of progesterone receptor agonists having a tetracyclic dibenzo-oxazepine structure 1. In this paper, the synthesis and structure-activity relationships of this new class are described. This work led to the identification of potent progesterone agonists up to 1 nM activi...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2008-02, Vol.18 (4), p.1461-1467
Main Authors: Dols, Paul P M A, Folmer, Brigitte J B, Hamersma, Hans, Kuil, Cor W, Lucas, Hans, Ollero, Lourdes, Rewinkel, Jos B M, Hermkens, Pedro H H
Format: Article
Language:English
Subjects:
Acetamides
Binding Sites
Fluoroacetates
Models, Molecular
Oxazepines - chemistry
Oxazepines - pharmacology
Progesterone - chemistry
Receptors, Progesterone - agonists
Structure-Activity Relationship
Trifluoroacetic Acid - chemistry
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Summary:We have developed a new class of progesterone receptor agonists having a tetracyclic dibenzo-oxazepine structure 1. In this paper, the synthesis and structure-activity relationships of this new class are described. This work led to the identification of potent progesterone agonists up to 1 nM activity. Substitution at positions 6, 7 and 1 has proven to be crucial for activity, indicating that probably these positions are involved in important interactions with the receptor.
ISSN:0960-894X
0968-0896
1464-3405
1464-3391
DOI:10.1016/j.bmcl.2007.12.065