title: Water soluble prodrugs of the antitumor agent 3-[(3-amino-4-methoxy)phenyl]-2-(3,4,5-trimethoxyphenyl)cyclopent-2-ene-1-one.
abstract: Fourteen prodrugs of the antitumor agent 3-[(3-amino-4-methoxy)phenyl]-2-(3,4,5-trimethoxyphenyl)cyclopent-2-ene-1-one (1) were prepared to improve its water solubility and potency. These prodrugs include alpha-amino acid (1a-1h), aliphatic amino acid (1i-1l), phosphoramidate (1m), and phosphate (1n) derivatives. All of the prodrugs showed improved water solubility. A number of the amino acid prodrugs (1a, 1b, 1d-1f, 1h, 1j, and 1k) exhibited more potent antitumor activity compared to the parent compound (1). The phosphate prodrug 1n also offered a potent antitumor activity, but the phosphoramidate 1m did not show any antitumor activity in vivo. None of the prodrugs exhibited significant toxicities in mice. These results indicate that the design and preparation of the amino acid prodrugs (1a, 1b, 1d-1f, 1h, 1j, and 1k) and phosphate prodrug (1n) are beneficial for enhancing the antitumor activity of 1. The similar approaches may be used to improve water solubility and bioactivity of other poorly soluble aromatic amines.
authors.affiliation: College of Pharmacy, Chungnam National University, Taejon 305-764, South Korea. ahnbj@cnu.ac.kr
authors.forename: Nguyen-Hai
authors.initials: NH
authors.lastname: Nam
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: You
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Hong
authors.forename: Hwan-Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Byung-Zun
authors.initials: BZ
authors.lastname: Ahn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012995:Solubility; D014407:Tumor Cells, Cultured
chemical_list: C478788:3-((3-amino-4-methoxy)phenyl)-2-(3,4,5-trimethoxyphenyl)cyclopent-2-ene-1-one; D000970:Antineoplastic Agents; D003517:Cyclopentanes; D007202:Indicators and Reagents; D011355:Prodrugs