Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095), a high affinity non-steroidal agonist for the estrogen receptor.
1-Ethyl-2-(4-hydroxyphenyl)pyrrolo[2,1,5-cd]indolizine (NNC 45-0095) is a novel compound which represents the parent pharmacophore structure of a series of pyrrolo[2,1,5-cd]indolizine derivatives with mixed estrogen agonist/antagonist properties. NNC 45-0095 binds with high affinity to the estrogen receptor (IC50=9.5 nM) and exhibits full protection of bone loss in the ovariectomized mouse model for post-menopausal osteoporosis.
Jørgensen
A S
AS
Health Care Discovery & Preclinical Development, Novo Nordisk A/S, Måløv, Denmark.
Jacobsen
P
P
Christiansen
L B
LB
Bury
P S
PS
Kanstrup
A
A
Thorpe
S M
SM
Bain
S
S
Naerum
L
L
Wassermann
K
K
D000818:Animals; D001667:Binding, Competitive; D001681:Biological Assay; D015519:Bone Density / Q000187:drug effects; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004195:Disease Models, Animal; D004341:Drug Evaluation; D004958:Estradiol / Q000378:metabolism; D015914:Estrogen Replacement Therapy; D005260:Female; D007212:Indolizines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051379:Mice; D009215:Myometrium / Q000737:chemistry / Q000648:ultrastructure; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011960:Receptors, Estrogen / Q000819:agonists* / Q000378:metabolism
D007212:Indolizines; D011758:Pyrroles; D011960:Receptors, Estrogen; D004958:Estradiol; C407730:NNC 45-0095