Method of modulating NF-kB activity

US6642215B2 · kind B2 · utility

Assignee

• Leo Pharma A/S · DK

Inventors

• Mogens Winkel Madsen · Tjele, DK
• Lone Olsen · Taastrup, DK

Key dates

• Filing date: May 24, 2002
• Grant date: Nov 4, 2003
• Expiry date: May 24, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D401/12
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

A method of modulating the level of activated, NF-&kgr;B in cells by contacting cells with a cyanoguanidine compound of general formula I whereinn is 0, 1 or 2;each R independently represents halogen, trifluoromethyl, hydroxy, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, nitro, cyano, amino, sulfo or carboxy groups;Q is a straight or branched, saturated or unsaturated C4-20 divalent hydrocarbon radical;X is a bond, O, S, amino, carbonyl, carbonylamino, aminocarbonyl, oxycarbonyloxy, oxycarbonyl, carbonyloxy, aminocarbonyloxy, aminothiocarbonyloxy, oxycarbonylamino or oxythiocarbonylamino;A is di-(C1-4 alkoxy)phosphinoyloxy, C1-4 alkoxycarbonyl, C1-4 alkoxycarbonylamino, saturated or unsaturated C3-12 carbocyclic ring or C3-12 heterocarbocyclic ring optionally substituted with one or more R1; R1 being independently selected from the group consisting of halogen, trifluoromethyl, hydroxy, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, nitro, cyano, amino, carboxy, sulfo, carboxamido, sulfamoyl or C1-4 hydroxyalkyl;or a pharmaceutically acceptable salt, N-oxide or N-substituted prodrug thereof, in an amount effective to modulate the activity of IKK.