Compounds for reversing drug resistance

US6297216A · kind A · utility

Assignee

• Solvo Biotechnology · HU

Inventors

• Balázs Sarkadi · Tapolca, HU
• Janos Seprodi · Budapest, HU
• Orsolya Csuka · Budapest, HU
• Maria Magocsi · Budapest, HU
• Imre Mezo · Budapest, HU
• Istvan Palyi · Budapest, HU
• Istvan Teplan · Budapest, HU
• Zsolt Vadasz · Budapest, HU
• Borbala Vincze · Budapest, HU

Key dates

• Filing date: Feb 19, 1997
• Grant date: Oct 2, 2001
• Expiry date: Feb 19, 2017

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K38/00
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention features novel peptide derivatives called Reversins, and provides for their use in a method of reducing the activity of the multi-drug transporter protein MDR1 in order to overcome multidrug resistance in a mammal. The peptide derivatives are of the formula (I) X.sup.1.sub.n -X.sup.2 -X.sup.3 (X.sup.4).sub.n -X.sup.5, wherein n is 0 or 1, and each n is the same or different; X.sup.1 is BOC, BOC-Asu, Z-Asu, benzyloxycarbonyl, Glu(OBzl)-OBzl, Trp-OMe, Trp-Phe-OMe, Phe-Trp-OMe, Phe-Phe-OtBu, Trp-Trp-OtBu, indoloacetyl, benzoyl, an alkylanine of 1-4 carbons, dibenzylamide, tryptamide, 1-amino-adamantine, aminomethylcyclohexane, indoline, phenylethylamide or dicyclohexylamide; X.sup.2 is Glu(OBzl), Asp(OBzl), succinyl, O,O-dibenzoyltartaroyl, diphenoyl, muconyl, Thx, Cpa, Asu, Nal, Pen, Phg, Dbt, Lys(BOC), Lys(Z), Cys(Bzl), Thr(Bzl), Glu(OtBu), tert.-Leu, Leu, Nle, Pro, Phe, Tyr(Bzl), or Ser(Bal); X.sup.3 is Asp, Asu, Lys, Glu, Trp, Thx, Cpa, Nal, Pen, Phg, Dbt, Glu(OtBu), tert.-Leu, Leu, Nle, Pro, Tyr, Phe, or Tyr(Bzl); X.sup.4 is BOC-Glu(OBzl), Glu(OBzl), Asu, OBzl, Bzl, BOC, BOC-Lys(BOC), Z-Glu(OtBu), Asp(OBzl), Asp(OBz)-OBzl, benzyloxycarbonyl, O-(cyclo-hexyl), fluoren…