Kappa receptor opioid peptides

US5965701A · kind A · utility

Assignee

• Ferring B.V. · NL

Inventors

• Jean-Louis Junien · Sèvres, FR
• Pierre Riviere · San Diego, US
• Claudio D. Schteingart · San Diego, US
• Javier Sueiras Diaz · Village of La Jolla, US
• Jerzy Trojnar · Vintrie, SE
• Todd Vanderah · Tucson, US

Key dates

• Filing date: Dec 23, 1997
• Grant date: Oct 12, 1999
• Expiry date: Dec 23, 2017

Classification

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

Abstract

Peptides which exhibit high selectivity for the kappa opioid receptor (KOR) and long duration of peripheral action without significant entry into the brain are created which are sequences of four D-isomer amino acid residues having a C-terminus which is a mono or di-substituted amide. Representative compounds, which have an affinity for the KOR at least 1,000 times their affinity for the mu opioid receptor and an ED.sub.50 of not greater than about 0.5 mg/kg, include EQU H-D-Phe-D-Phe-D-Nle-D-Arg-NHEt, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-morpholinyl, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-NH-4-picolyl, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-NHPr, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-thiomorpholinyl, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-NEt.sub.2, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-NHMe, EQU H-D-Phe-D-Phe-D-Leu-D-Orn-morpholinyl, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-NHhEt, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-NH-cyclopropyl, EQU H-D-Ala(2Thi)-D-4Cpa-D-Leu-D-Arg-morpholinyl, EQU H-D-Phe-D-Phe-D-Nle-D-Arg-piperidinyl, EQU H-D-Phe-D-Phe-D-Leu-D-Orn-NHEt, EQU H-D-Phe-D-Phe-D-Leu-D-Lys-morpholinyl, and EQU H-D-Phe-D-Phe-D-Nle-D-Arg-piperazinyl.