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 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.
Dols
Paul P M A
PP
Department of Medicinal Chemistry, N.V. Organon, PO Box 20, 5340 BH Oss, The Netherlands.
Folmer
Brigitte J B
BJ
Hamersma
Hans
H
Kuil
Cor W
CW
Lucas
Hans
H
Ollero
Lourdes
L
Rewinkel
Jos B M
JB
Hermkens
Pedro H H
PH
D000081:Acetamides; D001665:Binding Sites; D005463:Fluoroacetates; D008958:Models, Molecular; D010077:Oxazepines / Q000737:chemistry* / Q000494:pharmacology*; D011374:Progesterone / Q000737:chemistry; D011980:Receptors, Progesterone / Q000819:agonists*; D013329:Structure-Activity Relationship; D014269:Trifluoroacetic Acid / Q000737:chemistry
D000081:Acetamides; D005463:Fluoroacetates; D010077:Oxazepines; D011980:Receptors, Progesterone; C030688:trifluoroacetamide; D011374:Progesterone; D014269:Trifluoroacetic Acid