𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Synthesis and deuterium labelling of the pure selective estrogen receptor modulator (SERM) acolbifene glucuronides

✍ Scribed by Jean-Yves Sancéau; Denis Larouche; Brigitte Caron; Patrick Bélanger; Agnès Coquet; Alain Bélanger; Fernand Labrie; Sylvain Gauthier

Publisher
John Wiley and Sons
Year
2007
Tongue
French
Weight
202 KB
Volume
50
Category
Article
ISSN
0022-2135

No coin nor oath required. For personal study only.

✦ Synopsis

Acolbifene (EM-652 Á HCl, SCH 57068 Á HCl), a highly potent and orally active selective estrogen receptor modulator (SERM), is at late stage clinical development for the treatment of estrogen-sensitive breast cancer. Acolbifene-7-glucuronide 1 (major) and acolbifene-4 0 -glucuronide 2 (minor) were identified as metabolites of acolbifene in the human. The two monoglucuronides and a diglucuronide 3 as well as the corresponding 2 H-labelled derivatives 4-6 were synthesised for use as preclinical and clinical standards for LC-MS/MS analysis. All glucuronides were prepared by the Schmidt glycosylation of monoprotected acolbifene with a glucuronyl imidate at À108C to prevent epimerisation at the C-2 position. The two monoglucuronides 1 and 2 of acolbifene were separated by semi-preparative HPLC. Incorporation of three deuteriums was achieved by alkylation of chromanone 15 with C 2 H 3 MgI followed by dehydration with C 2 H 3 CO 2 2 H/ 2 H 2 O. After chemical resolution and salt neutralisation,

[ 2 H 3 ]acolbifene 19 was obtained with 99.4% enantiomeric purity and >98% isotopic purity.

📜 SIMILAR VOLUMES

Synthesis of 14C-labelled EM-800 (SCH 57
Synthesis of 14C-labelled EM-800 (SCH 57050) and EM-652·HCl (SCH 57068·HCl, acolbifene), pure selective estrogen receptor modulators
✍ Jean-Yves Sancéau; Fernand Labrie; Sylvain Gauthier 📂 Article 📅 2004 🏛 John Wiley and Sons 🌐 French ⚖ 166 KB

## Abstract EM‐800 (SCH 57050) and EM‐652·HCl (SCH 57068·HCl, acolbifene) are orally active pure selective estrogen receptor modulators. The corresponding ^14^C~2~‐radiolabelled compounds 1 and 2 were synthesized for metabolic studies with uniform labelling of two carbons within the benzene ring of

Synthesis, Biochemical Properties and Mo
Synthesis, Biochemical Properties and Molecular Modelling Studies of Organometallic Specific Estrogen Receptor Modulators (SERMs), the Ferrocifens and Hydroxyferrocifens: Evidence for an Antiproliferative Effect of Hydroxyferrocifens on both Hormone-Dependent and Hormone-Independent Breast Cancer Cell Lines
✍ Siden Top; Anne Vessières; Guy Leclercq; Jacques Quivy; J. Tang; J. Vaissermann; 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 390 KB 👁 2 views

## Abstract A series of ferrocene derivatives based upon the structure of the antiestrogenic drug tamoxifen or of its active metabolite hydroxytamoxifen has been prepared and named by analogy ferrocifens and hydroxyferrocifens. This series includes 1‐[4‐(O(CH~2~)~__n__~NMe~2~)phenyl]‐1‐phenyl‐2‐fer