RU54115, a tight-binding aromatase inhibitor potentially useful for the treatment of breast cancer

Delaisi, Christine; Doucet, B.; Hartmann, Catherine; Tric, Bernadette; Gourvest, Jean-François; Lesuisse, Dominique

doi:10.1016/0960-0760(92)90422-f

Cited by 9 publications

(4 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compound 40a, which is the most active in this series, decreases the estradiol level and inhibits the growth of endocrine tumours in vivo when used at a dose of 0.4 mg kg 71 . 49 Yet another type of 19-substituted androstanes, viz., 10b-(oxiran-2-yl)-and -(thiiran-2-yl)-steroids, represent competitive reversible AI. The synthesis of diastereomeric 10b-(epoxyethyl)estr-4-ene-3,17-diones (19S)-59 and (19R)-59 was carried out in four steps.…”

Section: Methods For the Synthesis Of Aromatase Inhibitors Of The And...mentioning

confidence: 99%

Substituted androstanes as aromatase inhibitors

Левина¹

1998

Russ. Chem. Rev.

View full text Add to dashboard Cite

The synthesis and structure ± activity relationships of inhibitors of steroid aromatase which catalyses the last stage of a multistep biotransformation of cholesterol into estrogens, viz., aromatisation of C 19 -steroids into C 18 -phenolic steroids, are discussed. Compounds of the androstane series which are structurally related to the natural substrate, viz., androst-4-ene-3,17dione, are the subjects of consideration. The review encompasses problems of synthesis of various substituted androstanes and their aromatase-inhibiting activities and structural requirements for selective specific aromatase inhibitors based on in vitro and in vivo structure ± activity studies of compounds synthesised, their biological properties and the results of clinical trials. Special attention is paid to practical applications of aromatase inhibitors in the treatment of hormone-dependent mammary and ovarian tumours as well as benign prostatic tumours. In writing this report, the author has used all the information currently available in the chemical, biochemical, endocrinological and medicinal literature as well as in patents. The bibliography includes 173 references.

show abstract

Section: Methods For the Synthesis Of Aromatase Inhibitors Of The And...mentioning

confidence: 99%

Substituted androstanes as aromatase inhibitors

Левина¹

1998

Russ. Chem. Rev.

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…During an investigation aimed at the search for potent aromatase inhibitors, we came across a new series of thio-substituted androstenedione analogs, one of them, RU54115 (7), has already been disclosed. 7 This compound is an excellent tight-binding aromatase inhibitor. 7 The object of the present paper is to present the chemistry, biochemistry, and structure-activity relationships of a series of new inhibitors related to 7.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structure−Activity Relationships of a New Family of Steroidal Aromatase Inhibitors. 1. Synthesis and Evaluation of a Series of Analogs Related to 19-[(Methylthio)methyl]androstenedione (RU54115)

et al. 1996

View full text Add to dashboard Cite

During the course of a study aimed at the search for new potent aromatase inhibitors, several new androstenedione analogs were synthesized and evaluated. This study led to the discovery of 19-[(methylthio)methyl]androsta-4,9(11)-diene-3,17-dione (7; RU54115) already described by our laboratory. The object of the present series of papers is to disclose the result of the structure-activity relationship studies that gave rise to this compound. This first part deals mainly with the substitution in the 19-position of the steroid nucleus. Several parameters were varied, the length of the chain and its rigidity and branching, as well as the nature of the heteroatom itself and its substitution. The interaction of these new compounds with human placental aromatase in competition with the substrate androstenedione was studied by difference visible spectroscopy. The in vivo aromatase-inhibiting activities were evaluated by measuring the estradiol lowering after oral administration of the compounds to PMSG-primed female rats.

show abstract

Inhibition of Cytochrome P450 Enzymes

Correia

Montellano

Cytochrome P450

View full text Add to dashboard Cite

RU54115, a tight-binding aromatase inhibitor potentially useful for the treatment of breast cancer

Cited by 9 publications

References 4 publications

Substituted androstanes as aromatase inhibitors

Substituted androstanes as aromatase inhibitors

Structure−Activity Relationships of a New Family of Steroidal Aromatase Inhibitors. 1. Synthesis and Evaluation of a Series of Analogs Related to 19-[(Methylthio)methyl]androstenedione (RU54115)

Inhibition of Cytochrome P450 Enzymes

Contact Info

Product

Resources

About