2-aryl-3-aroylbenzo[b]thiophenes useful for the treatment of est

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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514874, 549 49, 549 51, 549 57, A61K 3138, C07D40902

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active

061567868

ABSTRACT:
This invention provides methods which are useful for the inhibition of the various medical conditions associated with estrogen deprivation syndrome including osteoporosis and hyperlipidemia utilizing compounds of formula I: ##STR1##

REFERENCES:
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patent: 5514704 (1996-05-01), Carlson et al.
patent: 5532382 (1996-07-01), Carlson et al.
Draper et al., "effects of Raloxifene (LY139481 HCl) on Biochemical Markers of Bone and Lipid Metabolism Healthy Postmemopausal Women", Hong Kong, Fourth Int'l Symp. on Osteoporosis, Mar. 29, 1993.
Bryant et al., "Protection fro Bone Loss and Lowering of Serum Cholesterol in the Absence of Uterine Stimulation in Ovariectomized Rats", Am. Soc. Bone & Min. Res., Tampa, Sep. 18-22, 1993.
Bryant et al., "Raloxifene is a Tissue Specific Estrogen Agonist",Am Soc. Bone & Min. Res., Tampa, Sep. 18-22, 1993.
Frolik et al., "In Vivo and In Vitro Metabolism of Raloxifene", Am.Soc. Bone & Min. Res., Tampa Sep. 18-22, 1993.
Glasebrook et al., "Multiple Binding Sites for the Antiestrogen Raloxifene", Am Soc. Bone & Min. Res., Tampa, Sep. 18-22, 1993.
Black, et al., LY156758: A Unique Antiestrogen Displaying High Affinity for Estrogen Receptors, Negligible Estrogenic Activity and Near-Total Estrogen Antagonism in Vivo. Presented at the Fifth Annual San Antonio Breast Cancer Symposium, San Antonio, Texas, Nov. 5-6, 1982.
Black et al., The Antiestrogenic Action of LY139481: Species Uniformity Duration of Action and Kinetics of LY139481 Distribution In Vivo. Sixty-fifth Annual Meeting of the Endocrine Society, San Antonio, Texas, Jun. 8-10, 1983, abs. 93.
Black et al., Antagonism of Estrogen Action with a New Benzothiophene Derived Antiestrogen, Life Sciences, 32:1983, 1031-1036.
Black et al., The Relationship of the Antiestrogenic Efficacy of LY156758 too its Pharmacokinetics and Metabolism Following Oral Administration to Adult Ovariectomized Rats, Seventh International Congress of Endocrinology, Quebec City, Canada, Jul. 1-7, 1984, abs. 323.
Black et al., Synthesis and Antiestrogenic Activity of [3,4-Dihydro-2(4-methoxyphenyl)-1-napthalenyl] [4-[2-pyrrolidinyl) ethoxyl]-phenyl] methanone, methanesulfonic acid salt, Journal of Medicinal Chemistry 22:1979, 962-966.
Black et al., Antiestrogens 2, Structure Activity Studies in a Series of 3-Aroyl-2-arylbenzo[b]thiophene Derivatives Leading to [6-Hydroxy-2-(4-hydroxyphenyl)benzo[b] thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]-phenyl]methanone Hydrochloride (LY156758), a Remarkably Effective Estrogen Antagonist with Only Minimal Intrinsic Estrogenicity, J. Med.Chem. 27(8), 1984, 1057-166.

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