(2R*,3S*)-1-(/sup 125/I)Iodo-2,3-bis(4-hydroxyphenyl)pentane ((/sup 125/I)iodonorhexestrol) and (2R*,3S*)-1-(/sup 77/Br)Bromo-2,3-bis(4-hydroxyphenyl)pentane ((/sup 77/Br)bromonorhexestrol), two gamma-emitting estrogens that show receptor-mediated uptake by target tissues in vivo

Journal Article · Mon Nov 01 04:00:00 EST 1982 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00353a007· OSTI ID:6423007

Landvatter, S W; Katzenellenbogen, J A; McElvany, K D; Welch, M J

Two gamma-emitting estrogen analogues, (2R*,3S*)-1-(/sup 125/I)iodo-2,3-bis(4-hydroxyphenyl)pentane ((/sup 125/I)iodonorhexestrol) and (2R*,3S*)-1-(/sup 77/Br)bromo-2,3-bis(4-hydroxyphenyl)pentane ((/sup 77/Br)bromonorhexestrol), have been prepared by halide ion displacement on a labile trifluoromethanesulfonate derivative of a suitably protected precursor, followed by mild acid deprotection. Although halide displacement on a more stable tristrifluoromethanesulfonate derivative was successful, the basic conditions required for deprotection of this precursor resulted in destruction of the products by a base-induced spiroelimination reaction. In immature female rats, both of these halonorhexestrols demonstrated preferential uptake by the uterus that could be blocked selectively by coadministration of a large dose of unlabeled estradiol. In a double label comparison with 16 alpha-(/sup 125/I)iodo-17 beta-estradiol the uterine uptake of (/sup 77/Br)bromonorhexestrol was notably less selective. Stability studies in vitro and in vitro have indicated that both iodo- and bromonorhexestrol are quite labile, and this lability compromises the selectivity of their uptake by estrogen target tissues in vivo. p-Hydroxyphenethyl halides are known to be unusually prone to a base-catalyzed solvolysis, via cyclization of the phenolate to a spirocyclohexadienone intermediate. This unusual solvolytic mechanism may contribute to the lability of these halonorhexestrols in vivo.

• Research Organization: School of Chemical Sciences, University of Illinois, Urbana
• OSTI ID: 6423007
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 25:11; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400702 -- Radiochemistry & Nuclear Chemistry-- Properties of Radioactive Materials
550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BROMINE 77
BROMINE ISOTOPES
CHEMICAL PREPARATION
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ESTROGENS
FEMALE GENITALS
HORMONES
IN VIVO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPES
RADIOPHARMACEUTICALS
REACTION KINETICS
RECEPTORS
STEROID HORMONES
SYNTHESIS
UPTAKE
UTERUS