185416-72-2Relevant academic research and scientific papers
Benzothiophene and naphthalene derived constrained SERMs
Wallace, Owen B.,Bryant, Henry U.,Shetler, Pamela K.,Adrian, Mary D.,Geiser, Andrew G.
, p. 5103 - 5106 (2007/10/03)
The synthesis and biological evaluation of two series of conformationally restricted SERMs are disclosed. In each series (benzothiophene or naphthalene), the ligand side chain is constrained to adopt a defined orientation. The orientation of the side chain has a significant impact on functional activity.
Benzothiophene compounds
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, (2008/06/13)
The present invention relates to compounds of formula I I wherein R1 is -H, -OH, -O(C1-C4 alkyl), -OCOC6H5, -OCO(C1-C6 alkyl), or -OSO2(C4-C6 alkyl); R2 is 1-naphthyl, 2-naphthyl, 2-thienyl, 3-thienyl, benzothienyl, or -CH2C6H5; any of which may b
Benzothiophene compounds
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, (2008/06/13)
The present invention relates to compounds of formula I wherein, ???R1is -H, -OH, -O(C1-C4alkyl), -OCOC6H5, -OCO(C1-C6alkyl), or -OSO2(C4-C6alkyl
Structure-activity relationships of selective estrogen receptor modulators: Modifications to the 2-arylbenzothiophene core of raloxifene
Grese, Timothy A.,Cho, Stephen,Finley, Don R.,Godfrey, Alexander G.,Jones, Charles D.,Lugar III, Charles W.,Martin, Michael J.,Matsumoto, Ken,Pennington, Lewis D.,Winter, Mark A.,Adrian, M. Dee,Cole, Harlan W.,Magee, David E.,Phillips, D. Lynn,Rowley, Ellen R.,Short, Lorri L.,Glasebrook, Andrew L.,Bryant, Henry U.
, p. 146 - 167 (2007/10/03)
The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'- substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7- position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6- carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.
