title: Estrogen receptor ligands. Part 5: The SAR of dihydrobenzoxathiins containing modified basic side chains.
abstract: Dihydrobenzoxathiin analogs (1-11) with modifications on the basic side chain region were prepared and evaluated for estrogen/anti-estrogen activity in both in vitro and in vivo models. The compounds generally maintained a high degree of selectivity for ERalpha over ERbeta, similar to the original lead compound I. Many of the compounds also maintained high potency in the inhibition of human carcinoma MCF-7 cell growth. However, all were less potent in the inhibition of estradiol-triggered uterine growth. This work demonstrates the sensitive nature of modification to the antagonist basic side chain region.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, 800B-107, Rahway, NJ 07065, USA. qiang_tan@merck.com
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tan
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Birzin
authors.forename: Wanda
authors.initials: W
authors.lastname: Chan
authors.forename: Yi
authors.initials: Y
authors.lastname: Tien Yang
authors.forename: Lee-Yuh
authors.initials: LY
authors.lastname: Pai
authors.forename: Edward C
authors.initials: EC
authors.lastname: Hayes
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: DaSilva
authors.forename: Frank
authors.initials: F
authors.lastname: DiNinno
authors.forename: Susan P
authors.initials: SP
authors.lastname: Rohrer
authors.forename: James M
authors.initials: JM
authors.lastname: Schaeffer
authors.forename: Milton L
authors.initials: ML
authors.lastname: Hammond
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D004965:Estrogen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors; D006801:Humans; D008024:Ligands; D010075:Oxathiins / Q000138:chemical synthesis* / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D010075:Oxathiins; D011960:Receptors, Estrogen