Amino-and mercurio-substituted 4',5'-dihydropsoralens and therapeutical uses thereof

US6255324A · kind A · utility

Inventors

• Ned D. Heindel · Easton, US
• Jeffrey D. Laskin · Piscataway, US
• Diane E. Heck · Rumson, US
• Robert Rapp · Johnstown, US
• Marilyn S. Whittemore · Germantown, US
• Thomas E. McNeel · Memphis, US
• Ivan Jabin · Le Havre, FR

Key dates

• Filing date: Nov 25, 1998
• Grant date: Jul 3, 2001
• Expiry date: Nov 25, 2018

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07F3/14
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

5'-substituted, 4',5'-dihydropsoralen compounds (5) bearing tertiary amines (and salts thereof), quaternary ammonium moieties or organomercurial moieties are described. ##STR1## Also described are 2-substituted mercurimethyl-2-3-dihydro-benzofurans of forumla (7): ##STR2## Also reported are versatile direct syntheses through a hitherto unknown compounds such as 3-R-4,8-dimethyl-4',5'-dihydro-5'-bromomethylpsoralen or a 3-R-4,8-dimethyl-4', 5'-dihydro-5'-iodomethylpsoralen to prepare a structurally diverse array of partially reduced psoralens and benzofurans. The presence of a permanent ammonium charge in these psoralens precludes membrane passage and the mono-unsaturation precludes the cross-linking of nuclear DNA, thereby minimizing the mutagenic/carcinogenic side effects long associated with psoralen-derived therapies. The presence of a mercury functionality provides a reactive cell-binding group on these psoralens with unique cytotoxicity without light activation and an enhancement of cytotoxicity activity upon light activation. The invention also relates to These partially reduced and quaternized psoralens, amino-substituted psoralens, and mercurio psoralens display impressive …