Synthesis of a novel pentagastrin-drug conjugate for a targeted tumor therapy.

Abstract

The synthesis of the novel pentagastrin seco-CBI conjugate 3, which is based on the highly cytotoxic antitumor antibiotic (+)-duocarmycin SA (1), is reported. A key step in the synthesis is the palladium-catalyzed carbonylation of aryl bromide 7 to give the benzyl ester 16, which is transformed into the new seco-CBI derivative 21 bearing a carboxylic acid ester moiety. Subsequent transformation of 21 into an activated ester followed by the introduction of beta-alanine and tetragastrin led to the new pentagastrin drug 3 that contains a peptide moiety for targeting cancer cells expressing CCK-B/gastrin receptors.

• Authors: Lutz F Tietze, Olaf Panknin, Felix Major, Birgit Krewer
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 14 Issue 9 Pg. 2811-8 ( 2008) ISSN: 0947-6539 [Print] Germany
• PMID: 18214880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 1-chloromethyl-5-hydroxy-3-(5,6,7-trimethoxyindole-2-carbonyl)-2,3-dihydro-1H-benz(e)indole-7-carboxylic acid (beta-alanyl-tryptophyl-methionyl-aspartyl-phenylalanineamidyl)amide
• Antineoplastic Agents
• Duocarmycins
• Esters
• Indoles
• Pyrroles
• Receptor, Cholecystokinin B
• duocarmycin SA
• Palladium
• Pentagastrin

Topics

• Antineoplastic Agents (chemical synthesis, chemistry)
• Catalysis
• Cell Proliferation (drug effects)
• Drug Delivery Systems
• Duocarmycins
• Esters (chemistry)
• Indoles (chemical synthesis, chemistry)
• Molecular Structure
• Palladium (chemistry)
• Pentagastrin (analogs & derivatives, chemical synthesis, chemistry)
• Pyrroles (chemistry)
• Receptor, Cholecystokinin B (biosynthesis, drug effects)