title: Design, synthesis and evaluation of retinoids with novel bulky hydrophobic partial structures.
abstract: Many synthetic retinoids contain an aromatic structure with a bulky hydrophobic fragment. In order to obtain retinoids with therapeutic potential that do not bind to or activate retinoic acid X receptors (RXRs), we focused on the introduction of novel hydrophobic moieties, that is, metacyclophane, phenalene and benzoheptalene derivatives. The designed compounds were synthesized and their agonistic activities towards RARs and RXRs were evaluated. Most of the active compounds showed selectivity for RARα and RARβ over RARγ, and higher RARβ transactivating activity seemed to correlate with higher cell differentiation-inducing activity towards promyelocytic leukemia cell line HL-60. These compounds showed no agonistic activity towards RXRs.
authors.affiliation: Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Setagaya-ku, Tokyo 158-0094, Japan. yamano@itsuu.or.jp
authors.forename: Yohei
authors.initials: Y
authors.lastname: Amano
authors.forename: Masayuki
authors.initials: M
authors.lastname: Noguchi
authors.forename: Madoka
authors.initials: M
authors.lastname: Nakagomi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Muratake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukasawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Shudo
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D015195:Drug Design; D018922:HL-60 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D047488:Retinoid X Receptors / Q000819:agonists*; D012176:Retinoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids