Synthesis of a novel pentagastrin-drug conjugate for a targeted tumor therapy.
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.
Tietze
Lutz F
LF
Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, Tammannstrass2, 37077 Göttingen, Germany. ltietze@gwdg.de
Panknin
Olaf
O
Major
Felix
F
Krewer
Birgit
B
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D000080890:Duocarmycins; D004952:Esters / Q000737:chemistry; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D010418:Pentagastrin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry; D043887:Receptor, Cholecystokinin B / Q000096:biosynthesis / Q000187:drug effects
C529528:1-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; D000970:Antineoplastic Agents; D000080890:Duocarmycins; D004952:Esters; D007211:Indoles; D011758:Pyrroles; D043887:Receptor, Cholecystokinin B; C066098:duocarmycin SA; D010165:Palladium; D010418:Pentagastrin