Synthesis and pharmacological evaluation of novel cis-3,4-diaryl-hydroxychromanes as high affinity partial agonists for the estrogen receptor.
The syntheses and in vitro pharmacological evaluation of a number of cis-3,4-diaryl-hydroxy-chromanes are reported, along with the results of a thorough in vivo profiling of the tissue-selective estrogen partial-agonist NNC 45-0781 [3, (-)-(3S,4R)-7-hydroxy-3-phenyl-4-(4-(2-pyrrolidinoethoxy)phenyl)chromane]. These studies showed that NNC 45-0781 is a very promising candidate for the prevention of post-menopausal osteoporosis, and the treatment of other health issues related to the loss of endogenous estrogen production.
Bury
Paul S
PS
Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark. pjac@novonordisk.com
Christiansen
Lise B
LB
Jacobsen
Poul
P
Jørgensen
Anker S
AS
Kanstrup
Anders
A
Naerum
Lars
L
Bain
Steven
S
Fledelius
Christian
C
Gissel
Birgitte
B
Hansen
Birgit S
BS
Korsgaard
Niels
N
Thorpe
Susan M
SM
Wassermann
Karsten
K
D000818:Animals; D015519:Bone Density; D002784:Cholesterol / Q000097:blood; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000819:agonists*; D014621:Vagina / Q000166:cytology
D002839:Chromans; D011960:Receptors, Estrogen; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat