N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation
A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in bindi...
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| Veröffentlicht in: | Journal of medicinal chemistry 2009-05, Vol.52 (9), p.2794-2798 |
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| container_title | Journal of medicinal chemistry |
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| creator | Nirschl, Alexandra A Zou, Yan Krystek, Stanley R Sutton, James C Simpkins, Ligaya M Lupisella, John A Kuhns, Joyce E Seethala, Ramakrishna Golla, Rajasree Sleph, Paul G Beehler, Blake C Grover, Gary J Egan, Donald Fura, Aberra Vyas, Viral P Li, Yi-Xin Sack, John S Kish, Kevin F An, Yongmi Bryson, James A Gougoutas, Jack Z DiMarco, John Zahler, Robert Ostrowski, Jacek Hamann, Lawrence G |
| description | A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model. |
| doi_str_mv | 10.1021/jm801583j |
| format | Article |
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(ANL), Argonne, IL (United States)</creatorcontrib><title>N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. 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(ANL), Argonne, IL (United States)</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nirschl, Alexandra A</au><au>Zou, Yan</au><au>Krystek, Stanley R</au><au>Sutton, James C</au><au>Simpkins, Ligaya M</au><au>Lupisella, John A</au><au>Kuhns, Joyce E</au><au>Seethala, Ramakrishna</au><au>Golla, Rajasree</au><au>Sleph, Paul G</au><au>Beehler, Blake C</au><au>Grover, Gary J</au><au>Egan, Donald</au><au>Fura, Aberra</au><au>Vyas, Viral P</au><au>Li, Yi-Xin</au><au>Sack, John S</au><au>Kish, Kevin F</au><au>An, Yongmi</au><au>Bryson, James A</au><au>Gougoutas, Jack Z</au><au>DiMarco, John</au><au>Zahler, Robert</au><au>Ostrowski, Jacek</au><au>Hamann, Lawrence G</au><aucorp>Argonne National Lab. (ANL), Argonne, IL (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2009-05-14</date><risdate>2009</risdate><volume>52</volume><issue>9</issue><spage>2794</spage><epage>2798</epage><pages>2794-2798</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><abstract>A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.</abstract><cop>Columbus, OH</cop><pub>American Chemical Society</pub><pmid>19351168</pmid><doi>10.1021/jm801583j</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of medicinal chemistry, 2009-05, Vol.52 (9), p.2794-2798 |
| issn | 0022-2623 1520-4804 |
| language | eng |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | ANDROGENS Animals BASIC BIOLOGICAL SCIENCES Biological and medical sciences Crystallography, X-Ray FUNCTIONALS GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE Hormones. Endocrine system Humans Hydrogen-Ion Concentration IN VITRO INSTABILITY Male Medical sciences Models, Molecular Molecular Conformation MUSCLES Muscles - drug effects Muscles - metabolism Oxazoles - chemistry Oxazoles - pharmacology Pharmacology. Drug treatments Prostate - drug effects Prostate - metabolism Rats RODENTS Substrate Specificity SYNTHESIS |
| title | N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation |
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