10321. Lasofoxifene

Nomenclature

CAS number: 180916-16-9
(5R,6S)-5,6,7,8-Tetrahydro-6-phenyl-5-[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]-2-naphthalenol; ()-cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol.
C28H31NO2; mol wt 413.55.
C 81.32%, H 7.56%, N 3.39%, O 7.74%.

Description and references

Selective estrogen receptor modulator (SERM). Partial estrogen agonist. Prepn: K. O. Cameron, P. A. Jardine, WO 9621656; K. O. Cameron et al., US 5552412 (1996, 1996 both to Pfizer). Structure-activity relationship: R. L. Rosati et al., J. Med. Chem. 41, 2928 (1998) DOI PubMed. Improved synthesis: X. Yang et al., Org. Lett. 2, 4025 (2000) DOI PubMed; Y. Sano et al., Chem. Lett. 36, 40 (2007) DOI. Crystal structure of complex with estrogen receptor α domain: F. F. Vajdos et al., Protein Sci. 16, 897 (2007) DOI PubMed. Clinical compaison with raloxifene, q.v., in postmenopausal osteoporosis: M. R. McClung et al., Menopause 13, 377 (2006) DOI PubMed. Review of preclinical studies: H. Z. Ke et al., J. Am. Aging Assoc. 25, 87-100 (2002) DOI; of pharmacology and clinical experience: L. Gennari et al., Expert Opin. Invest. Drugs 15, 1091-1103 (2006) DOI PubMed.

Chemical structure

Derivative

Hydrochloride.

Nomenclature

CAS number: 180915-85-9
C28H31NO2.HCl; mol wt 450.01.
C 74.73%, H 7.17%, N 3.11%, O 7.11%, Cl 7.88%.

Properties

Crystals from acetonitrile/methylene chloride, mp 260-263°. [α]D 330.6° (c = 0.05 in CH2Cl2).

Derivative

Tartrate.

Nomenclature

CAS number: 190791-29-8
CP-336156; Fablyn (Pfizer); Oporia (Pfizer).
C28H31NO2.C4H6O6; mol wt 563.64.
C 68.19%, H 6.62%, N 2.49%, O 22.71%.

Description and references

Prepn: C. K. Chiu, M. Meltz, US 5948809 (1999 to Pfizer). HPLC analysis of dissolution properties: J. S. Space et al., J. Pharm. Biomed. Anal. 44, 1064 (2007) DOI PubMed.

Properties

White solid from 95% ethanol.

Therapeutic Category

Antiosteoporotic.

Keywords

Antiosteoporotic; Selective Estrogen Receptor Modulator (SERM)