Ethamoxytriphetol

Ethamoxytriphetol

Systematic (IUPAC) name
1-[4-[2-(Diethylamino)ethoxy]phenyl]-2-(4-methoxyphenyl)-1-phenylethanol
Identifiers
CAS Number	67-98-1
PubChem	CID: 6222
ChemSpider	5987
Synonyms	NSC-19857
Chemical data
Formula	C27H33NO3
Molecular mass	419.55582 g/mol
SMILES CCN(CC)CCOC1=CC=C(C=C1)C(CC2=CC=C(C=C2)OC)(C3=CC=CC=C3)O
InChI InChI=1S/C27H33NO3/c1-4-28(5-2)19-20-31-26-17-13-24(14-18-26)27(29,23-9-7-6-8-10-23)21-22-11-15-25(30-3)16-12-22/h6-18,29H,4-5,19-21H2,1-3H3 Key:KDYQVUUCWUPJGE-UHFFFAOYSA-N

Ethamoxytriphetol (developmental code name MER-25) is a synthetic, non-steroidal antiestrogen that was studied clinically in the late 1950s and early 1960s but was never marketed. MER-25 was first reported in 1958, and was the first antiestrogen to be discovered. It has been described as "essentially devoid of estrogenic activity" and as having "very low estrogenic activity in all species tested". However, some estrogenic effects in the uterus have been observed, so it is not a pure antiestrogen (that is, a silent antagonist of the estrogen receptor (ER)) but is, instead, technically a selective estrogen receptor modulator (SERM). For all intents and purposes, it is a nearly pure antiestrogen, however.

MER-25 produces antifertility effects in animals, and garnered interest as a potential hormonal contraceptive. However, clinical development was discontinued due to its low potency and the incidence of unacceptable central nervous system side effects, including hallucinations and psychotic episodes, with higher doses. Prior to being discontinued, the drug was also administered by Roy Hertz to three patients with metastatic breast cancer and was found to provide relief from bone pain, presumably due to dissolution of bone metastases. This was the first such study of its kind of antiestrogen therapy for the treatment of breast cancer, and it led to the development of the highly successful tamoxifen for this indication a decade later. The drug was also evaluated for the purpose of ovulation induction and as a treatment of chronic mastitis and endometrial cancer before clinical development was stopped.

MER-25, a simple triphenylethanol derivative, is closely related structurally to the triphenylethylene (TPE) group of SERMs, which includes clomifene and tamoxifen. The drug, a derivative of the cholesterol-lowering agent triparanol (MER-29), was originally being studied in animals at Merrell Dow as a treatment for coronary artery disease. Its antiestrogen properties were discovered serendipitously when a young research endocrinologist at the company named Leonard Lerner, who was employed to study non-steroidal estrogen pharmacology, noted the structural similarity of MER-25 to estrogenic TPE derivatives and decided to test it for estrogenicity, only to find that it blocked the effects of estrogen instead. Lerner subsequently went on to be involved in the discovery of clomifene, the first considerably antiestrogenic TPE derivative to be characterized. The structure of clomifene is similar to that of its predecessor, MER-25.

See also

• Fulvestrant
• Chlorotrianisene
• Estrobin
• Broparestrol
• Raloxifene
• Nafoxidine
• Diethylstilbestrol
• Stilbestrol