(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 · Fri Jan 01 04:00:00 EST 1982 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00353a007· OSTI ID:7191382

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 7/12'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..cap 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 vivo have indicated that both iodo- and bromonorhexestrol was notably less selective. Stability studies in vitro and in vivo 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. 1 figure, 5 tables.

• Research Organization: Univ. of Illinois, Urbana
• OSTI ID: 7191382
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 25; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
560172 -- Radiation Effects-- Nuclide Kinetics & Toxicology-- Animals-- (-1987)
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKANES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
BROMINE 77
BROMINE ISOTOPES
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
ELECTRON CAPTURE RADIOISOTOPES
ESTROGENS
FEMALE GENITALS
GAMMA RADIATION
GLANDS
HORMONES
HYDROCARBONS
IMAGES
IN VITRO
IN VIVO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
IONIZING RADIATIONS
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MAMMARY GLANDS
MINUTES LIVING RADIOISOTOPES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PENTANE
PRECURSOR
RADIATIONS
RADIOISOTOPES
RADIOPHARMACEUTICALS
RATS
RECEPTORS
RODENTS
STEROID HORMONES
UPTAKE
UTERUS
VERTEBRATES