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Here, we describe the synthesis, biological profile, and mode of action against LXR isoforms, of two novel side chain bioisosteric analogues of DMHCA (\n 1<\/jats:bold>\n ) where the dimethylamide was replaced by a\n N<\/jats:italic>\n ,\n N<\/jats:italic>\n \u2010dimethyl carbamate (\n 2<\/jats:bold>\n ) or sulfamate (\n 3<\/jats:bold>\n ). These compounds were obtained in good yields via a simple synthetic sequence starting from stigmasterol, a readily available phytosterol byproduct from the soybean industry. Both analogues\n 2<\/jats:bold>\n and\n 3<\/jats:bold>\n exhibited agonistic activity comparable to DMHCA (\n 1<\/jats:bold>\n ) in luciferase reporter assays in human HEK\u2010293\u2009T cells, although sulfamate (\n 3<\/jats:bold>\n ) proved to be more effective (LXR\u03b1\/\n 1<\/jats:bold>\n pEC\n 50<\/jats:sub>\n \u2009=\u20096.4; LXR\u03b2\/\n 1<\/jats:bold>\n pEC\n 50<\/jats:sub>\n \u2009=\u20096.4; LXR\u03b1\/\n 2<\/jats:bold>\n pEC\n 50<\/jats:sub>\n \u2009=\u20095.3; LXR\u03b2\/\n 2<\/jats:bold>\n pEC\n 50<\/jats:sub>\n \u2009=\u20095.6; LXR\u03b1\/\n 3<\/jats:bold>\n pEC\n 50<\/jats:sub>\n \u2009=\u20096.0; LXR\u03b2\/\n 3<\/jats:bold>\n pEC\n 50<\/jats:sub>\n \u2009=\u20096.1). Molecular dynamics simulations of the LXR\u03b2\/ligand complexes confirmed a stable binding mode consistent with the dose\u2013response data in all cases. The results set the foundation for developing novel analogues based on these compounds, particularly with sulfamate (\n 3<\/jats:bold>\n ).\n <\/jats:p>","DOI":"10.1002\/cplu.202600007","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T16:01:49Z","timestamp":1777305709000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Carbamate and Sulfamate Bioisosteres of\n N<\/i>\n ,\n N<\/i>\n \u2010Dimethyl\u20103\u03b2\u2010Hydroxycholenamide as Ligands of the Liver X Receptors"],"prefix":"10.1002","volume":"91","author":[{"given":"Malena","family":"Pegenaute","sequence":"first","affiliation":[{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Org\u00e1nica Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9421-0613","authenticated-orcid":false,"given":"Micaela B.","family":"Pugliese","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Org\u00e1nica Universidad de Buenos Aires Buenos Aires Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)\u2013Universidad de Buenos Aires Unidad de Microan\u00e1lisis y M\u00e9todos F\u00edsicos en Qu\u00edmica Org\u00e1nica (UMYMFOR) Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Facundo","family":"Perez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Org\u00e1nica Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7295-2471","authenticated-orcid":false,"given":"Florencia","family":"Di Salvo","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)\u2013Universidad de Buenos Aires,.Instituto de Qu\u00edmica F\u00edsica de los Materiales Medio Ambiente y Energ\u00eda (INQUIMAE) Buenos Aires Argentina"},{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Inorg\u00e1nica Anal\u00edtica y Qu\u00edmica F\u00edsica Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7055-9721","authenticated-orcid":false,"given":"Rosana I.","family":"Misico","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Org\u00e1nica Universidad de Buenos Aires Buenos Aires Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)\u2013Universidad de Buenos Aires Unidad de Microan\u00e1lisis y M\u00e9todos F\u00edsicos en Qu\u00edmica Org\u00e1nica (UMYMFOR) Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3611-6577","authenticated-orcid":false,"given":"Mar\u00eda V.","family":"Dansey","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Org\u00e1nica Universidad de Buenos Aires Buenos Aires Argentina"},{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Biol\u00f3gica Universidad de Buenos Aires Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8841-2330","authenticated-orcid":false,"given":"Lautaro D.","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Org\u00e1nica Universidad de Buenos Aires Buenos Aires Argentina"},{"name":"Facultad de Ciencias Exactas y Naturales Departamento de Qu\u00edmica Biol\u00f3gica Universidad de Buenos Aires 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