Hartmann, Rolf W. and Schwarz, Walter and Schönenberger, Helmut (1983) Ring-substituted 1,2-dialkylated 1,2-bis(hydroxyphenyl)ethanes. 1. Synthesis and estrogen receptor binding affinity of 2,2'- and 3,3'-disubstituted hexestrols. Journal of medicinal chemistry 26 (8), pp. 1137-1144.
Full text not available from this repository.
The syntheses of sym. 3,3'- and 2,2'-disubstituted meso hexestrol derivs. (I) are described (3,3'-R = : OH (II) [79199-51-2], F (III) [74536-61-1], Cl (IV) [79140-57-1], Br [74536-64-4], I [55508-15-1], CH2NMe2 [85720-37-2], Me [10465-10-8], CH2OMe [85720-38-3], CH2OEt [85720-40-7], CH2OH [85720-41-8], NO2 [66877-40-5], NH2 [66877-41-6], NMe2 [85720-42-9], Ac [85720-43-0], and Et [85720-45-2]; 2,2'-R = : OH [85720-47-4], F [85720-49-6], Cl [85720-52-1], Br [85720-55-4], Me [85720-57-6], and Et [85720-58-7]). The synthesis of II-IV was accomplished by reductive coupling of the propiophenones with TiCl4/Zn and subsequent hydrogenation of the cis-3,4-diphenylhex-3-enes. The rest of the 3,3'-disubstituted derivs. were obtained by substitution of hexestrol [84-16-2], whereas the 2,2'-disubstituted derivs. were synthesized by coupling the 1-phenyl-1-propanols with TiCl3/LiAlH4 and sepn. of the meso diastereomers. The binding affinity of these compds. to the calf uterine estrogen receptor was measured relative to that of [3H]estradiol by a competitive binding assay. All test compds. showed relative binding affinity (RBA) values between 32 and <0.01% that of estradiol. Only meso-3,4-bis(2,4-dihydroxyphenyl)hexane showed an estrogen receptor binding affinity comparable to that of hexestrol (32 and 27%, resp.). Compds. exhibiting RBA values of >5% were evaluated in the mouse uterine wt. test. All of them showed uterotrophic activity. III and the 3,3'-CH3, 2,2'-OH, 2,2'-F, and 2,2'-CH3 derivs. were strongly active in very small doses (1 micro g/animal/day), whereas II and the 3,3'-NH2 deriv. produced full uterotrophic effects only in high doses and inhibited the estrone-stimulated uterine growth strongly in small doses (59 and 78% inhibition, resp.).
|Additional information (public):||CAN 99:33234 2-2 Mammalian Hormones 28231-25-6 Role: RCT (Reactant), RACT (Reactant or reagent) (acetylation of); 84-16-2D Role: BIOL (Biological study) (estrogen receptor-binding activity of, structure in relation to); 85720-39-4P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and alk. sapon. of); 10465-10-8P; 55508-15-1P; 66877-40-5P; 66877-41-6P; 74536-61-1P; 74536-64-4P; 79140-57-1P; 79199-51-2P; 85720-37-2P; 85720-38-3P; 85720-40-7P; 85720-41-8P; 85720-42-9P; 85720-43-0P; 85720-45-2P; 85720-47-4P; 85720-49-6P; 85720-52-1P; 85720-55-4P; 85720-57-6P; 85720-58-7P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and estrogen receptor-binding activity of); 74536-60-0P; 79140-65-1P; 85720-33-8P; 85720-44-1P; 85720-46-3P; 85720-48-5P; 85720-50-9P; 85720-53-2P; 85720-56-5P; 85720-59-8P; 85735-20-2P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. and ether cleavage of); 85720-34-9P; 85720-35-0P; 85720-36-1P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and hydrogenation of); 85720-54-3P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and redn. of); 830-99-9P; 23600-60-4P; 53773-75-4P; 85720-51-0P; 85720-60-1P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and reductive coupling of); 586-22-1; 1835-04-7; 4394-54-1; 13329-61-8 Role: RCT (Reactant), RACT (Reactant or reagent) (reductive coupling of)|
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Retired Professors > Prof. Schönenberger|
|Keywords:||Receptors Role: BIOL (Biological study) (for estrogen, hexestrol deriv. binding by) Estrogens Role: BIOL (Biological study) (receptor for, hexestrol deriv. binding by) Molecular structure-biological activity relationship (estrogen receptor-binding, of hexestrol derivs.) hydroxyphenylethane prepn estrogen receptor binding hexestrol deriv estrogen receptor binding structure activity hexestrol deriv|
|Subjects:||500 Science > 540 Chemistry & allied sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||12 Nov 2010 10:11|
|Last Modified:||12 Nov 2010 10:11|
- ASCII Citation
- Dublin Core
- HTML Citation
- OAI-ORE Resource Map (Atom Format)
- OAI-ORE Resource Map (RDF Format)
- Reference Manager
- Simple Metadata
Literature of the same author