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Structure–activity relationships of 2-, 4-, or 6-substituted estrogens as aromatase inhibitors
6alpha-Phenylestrone was the most powerful inhibitor among the estrogens studied, and its affinity was comparable to that of the androgen substrate androstenedione, indicating that the 17-carbonyl group plays a critical role in the formation of a thermodynamically stable enzyme-inhibitor complex. Expand
Structure–activity relationships of 3-deoxy androgens as aromatase inhibitors. synthesis and biochemical studies of 4-substituted 4-ene and 5-ene steroids
All of the steroids studied, except for 4-acetoxy-19-ol that was a non-competitive inhibitor of human placental aromatase, blocked aromat enzyme activity in a competitive manner. Expand
Inhibition of estrone sulfatase by aromatase inhibitor-based estrogen 3-sulfamates
The finding that estrone 3-sulfamate (EMATE) can be hydrolyzed and the pharmacological effect of the free estrogen contributes to the bioactivity of the sulfamate is useful for developing a new class of drugs having a dual function, ES inhibition and aromatase inhibition, for the treatment of breast cancer. Expand
Probing the active site of aromatase with 2-methyl-substituted androstenedione analogs
Kinetic analysis of the aromatization of androgens revealed that a good substrate was not essentially a good inhibitor for aromatase, indicating that a combination of 2beta- and 2alpha-methyl moieties is essential for the formation of a thermodynamically stable inhibitor-aromatase complex. Expand
Improved synthesis and molecular modeling of 4beta,19-dihydroxyandrost-5-en-17-one, an excellent inhibitor of aromatase.
The minimum energy conformation of the powerfull aromatase inhibitor 6 was obtained with the PM3 method and compared with that of the structurally related diol steroid, 4-ene-5beta,19-diol 3, a weak competitive inhibitor. Expand
Aromatization of androstenedione and 16α-hydroxyandrostenedione in human placental microsomes Kinetic analysis of inhibition by the 19-oxygenated and 3-deoxy analogs
The results suggest that the AD derivatives 1 are kinetically aromatized at a different site from the 16-OHAD derivatives 2, and do not exclude the idea that the placental microsomes have a single binding site. Expand
Aromatase inhibition by 4 beta,5 beta-epoxides of 16 alpha-hydroxyandrostenedione and its 19-oxygenated analogs, potential precursors of estriol production in the feto-placental unit.
The present results are consistent with the two binding sites theory in the active site of aromatase. Expand
Aromatase Inhibition by 4β,5β-Epoxides of 16α-Hydroxyandrostenedione and Its 19-Oxygenated Analogs, Potential Precursors of Estriol Production in the Feto-Placental Unit
To gain insight into the nature of the substrate binding site and the catalytic function of aromatase, we studied the inhibition of androstenedione aromatization byExpand
Improved Synthesis and Molecular Modeling of 4β,19-Dihydroxyandrost-5-en-17-one, an Excellent Inhibitor of Aromatase.
4β,19-Dihydroxyandrost-5-en-17-one (6) is an excellent competitive inhibitor of estrogen synthetase (aromatase). Alternate, improved synthesis of this inhibitor was established. Treatment ofExpand
4- and 6-(p-Sulphamoylphenyl)androstenediones: Studies of aromatase inhibitor-based oestrone sulphatase inhibition
The present findings of the oestrone sulphatase inhibition are disappointing, but such attempts may be valuable to develop a new class of drugs having a dual function, aromatase inhibitor and oestrogens-dependent breast cancer inhibitor, for the treatment of oestrogen- dependent breast cancer. Expand