Discovery and preclinical characterization of (+)-3-[4-(1- piperidinoethoxy)phenyl]spiro[indene- 1,1'-indane]-5,5'-diol hydrochloride: a promising nonsteroidal estrogen receptor agonist for hot flush.
In our studies of the development of a novel class of selective estrogen receptor modulators, (+)-3-[4-(1-piperidinoethoxy)phenyl]spiro[indene-1,1'-indane]-5,5'-diol hydrochloride (1) was found to be an estrogen receptor ligand with beneficial effects in rat models for human hot flush. Moreover, 1 was found to have beneficial effects on lipid and bone metabolism while maintaining marginal effects on the uterus and breasts. These findings suggest that 1 would provide a new treatment for hot flush.
Watanabe
Nobuhide
N
Chemistry Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Enoki-cho 33-94, Suita, Osaka 564-0053, Japan. nobuhide-watanabe@dainippon-pharm.co.jp
Ikeno
Akihisa
A
Minato
Hisao
H
Nakagawa
Hiroshi
H
Kohayakawa
Chie
C
Tsuji
Jun-ichi
J
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D004353:Drug Evaluation, Preclinical; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D007189:Indans / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D009021:Morphine Dependence / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000819:agonists* / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012881:Skin Temperature / Q000187:drug effects; D013141:Spiro Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects
C478564:3-(4-(1- piperidinoethoxy)phenyl)spiro(indene- 1,1'-indane)-5,5'-diol; D007189:Indans; D010880:Piperidines; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013141:Spiro Compounds; D009270:Naloxone; D004958:Estradiol; D002784:Cholesterol