title: Synthesis and pharmacological evaluation of novel cis-3,4-diaryl-hydroxychromanes as high affinity partial agonists for the estrogen receptor.
abstract: 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.
authors.affiliation: Novo Nordisk A/S, Novo Nordisk Park, DK-2760, Måløv, Denmark. pjac@novonordisk.com
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bury
authors.forename: Lise B
authors.initials: LB
authors.lastname: Christiansen
authors.forename: Poul
authors.initials: P
authors.lastname: Jacobsen
authors.forename: Anker S
authors.initials: AS
authors.lastname: Jørgensen
authors.forename: Anders
authors.initials: A
authors.lastname: Kanstrup
authors.forename: Lars
authors.initials: L
authors.lastname: Naerum
authors.forename: Steven
authors.initials: S
authors.lastname: Bain
authors.forename: Christian
authors.initials: C
authors.lastname: Fledelius
authors.forename: Birgitte
authors.initials: B
authors.lastname: Gissel
authors.forename: Birgit S
authors.initials: BS
authors.lastname: Hansen
authors.forename: Niels
authors.initials: N
authors.lastname: Korsgaard
authors.forename: Susan M
authors.initials: SM
authors.lastname: Thorpe
authors.forename: Karsten
authors.initials: K
authors.lastname: Wassermann
mesh_terms: 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
chemical_list: D002839:Chromans; D011960:Receptors, Estrogen; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat