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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Catalysis
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Cell Proliferation / drug effects
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Drug Delivery Systems
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Duocarmycins
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Esters / chemistry
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Indoles / chemical synthesis*
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Indoles / chemistry*
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Molecular Structure
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Palladium / chemistry
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Pentagastrin / analogs & derivatives*
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Pentagastrin / chemical synthesis
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Pentagastrin / chemistry*
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Pyrroles / chemistry
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Receptor, Cholecystokinin B / biosynthesis
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Receptor, Cholecystokinin B / drug effects
Substances
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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
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Antineoplastic Agents
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Duocarmycins
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Esters
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Indoles
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Pyrroles
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Receptor, Cholecystokinin B
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duocarmycin SA
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Palladium
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Pentagastrin