Histogranin-like peptides and non-peptides, processes for their preparation and uses thereof

US7183279B2 · kind B2 · utility

Assignee

• THE UNIVERSITY OF OTTAWA · CA

Inventors

• Simon Lemaire · Aylmer, CA
• Irma Bernatchez-Lemaire · Aylmer, CA
• Hoang-Thanh Le · Ottawa, CA

Key dates

• Filing date: May 25, 2006
• Grant date: Feb 27, 2007
• Expiry date: May 25, 2026

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K5/126
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention relates to new basic amino acid derivatives of general formulae I, II and III, and the preparation and use thereof in treatment of pain. The compounds have histogranin-like antinociceptive, morphine potentiating and COX-2 induction modulating activities.wherein:A is -hydrogen, —(C1–C8)alkyl or —(C1–C8)alkyl substituted by hydroxy;B is —(C1–C6)alkylguanidino, —(C1–C6)alkyl(4-imidazolyl), —(C1–C6)alkylamino, p-aminophenylalkyl(C1–C6)—, p-guanidinophenylalkyl(C1–C6)— or 4-pyridinylalkyl(C1–C6)—;D is —(CO)—, —(CO)—(C1–C6)alkylene or —(C1–C6)alkylene;E is a single bond or —(C1–C6)alkylene;Z is —NH2, —NH—(C1–C6)alkylcarboxamide, —NH— (C1–C6)alkyl, —NH— (N-benzyl), —NH-cyclo (C5–C7)alkyl, —NH-2-(1-piperidyl)ethyl, —NH-2-(1-pyrrolidyl)ethyl, —NH-2-(1-pyridyl)ethyl, —NH-2-(morpholino)ethyl, -morpholino, -piperidyl, —OH, —(C1–C6)alkoxy, —O-benzyl or —O-halobenzyl;R1, R2 and R3 are, independent of one another, -hydrogen, -arylcarbonylamino, —(C1–C6)alkoylamino, —(C1–C6)alkylamino, —(C1–C6)alkyloxy, —(C1–C6)alkylaminocarbonyl, -carboxy, —OH, -benzoyl, -p-halogenobenzoyl, -methyl, —S-(2,4-dinitrophenyl), —S-(3-nitro-2-pyridinesulfenyl), -sulfonyl, -trifluoromethyl, —(C1–C6)alkylam…