title: Synthesis and preliminary chemotherapeutic evaluation of the fully C-linked glucuronide of N-(4-hydroxyphenyl)retinamide.
abstract: All-trans retinoic acid analogues such as N-(4-hydroxyphenyl)retinamide (4-HPR) are effective chemopreventive and chemotherapeutic agents but their utility has been hampered by dose-limiting side effects. The glucuronide derivatives of 4-HPR, the oxygen-linked 4-HPROG and the carbon-linked 4-HPRCG, have been found to be more effective agents. The synthetic route to the fully C-linked analogue of 4-HPROG (4-HBRCG), which employs Suzuki coupling and Umpolung chemistries as key methodologies, is shown. The results of this study show 4-HBRCG to be an effective chemotherapeutic agent in a rat mammary tumor model while being devoid of classical retinoid toxicities.
authors.affiliation: Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Joel R
authors.initials: JR
authors.lastname: Walker
authors.forename: Galal
authors.initials: G
authors.lastname: Alshafie
authors.forename: Nirca
authors.initials: N
authors.lastname: Nieves
authors.forename: Jamie
authors.initials: J
authors.lastname: Ahrens
authors.forename: Margaret
authors.initials: M
authors.lastname: Clagett-Dame
authors.forename: Hussein
authors.initials: H
authors.lastname: Abou-Issa
authors.forename: Robert W
authors.initials: RW
authors.lastname: Curley
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D001943:Breast Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005260:Female; D017313:Fenretinide / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020719:Glucuronides / Q000737:chemistry*; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D020719:Glucuronides; D017313:Fenretinide; D015127:9,10-Dimethyl-1,2-benzanthracene