Von Angerer, Erwin and Knebel, Norbert and Schönenberger, Helmut and Engel, Juergen (1988) Diamineplatinum(II) complex compounds with a hydroxylated 2-phenylindole ring, procedure for their preparation, pharmaceutical compositions containing them, and their use as antitumor agents.
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The title compds. I [R1 = H, OH, C2-6 alkanoyloxy; R2, R5, R6 = H, halo; R3 = H, C1-6 alkyl; R4 = OH, C2-6 alkanoyloxy; Alk = C2-10 alkylene (4 neighboring CH2 can be replaced by 1,4-phenylene); AB = NHCH2CH2NH2, (H2NCH2)2CH, Q (R7 = H, C1-6 alkyl, Ph); X = equiv. physiol. tolerable anion], useful as antitumor agents with good tolerability, were prepd. by reaction of a tetrahaloplatinum (II) acid, a tetrahaloplatinum (II) complex salt with 2 monovalent or 1 divalent cation or a Pt(II) halide with indole compd. II. NaH in DMF was treated with 5-methoxy-2-(4-methoxyphenyl)-3-methylindole, then with Br(CH2)6Br to give 84% 1-(6-bromohexyl)-5-methoxy-2-(4-methoxyphenyl)-3-methylindole which reacted with (H2NCH2)2 in MeOH to give 1-[6-(2-aminoethylamine)hexyl]-5-methoxy-2-(4-methoxyphenyl)-3-methylindole (III). Ether cleavage of III with BBr3 gave 1-(2-aminoethylamino)-6-[5-hydroxy-2-(4-hydroxyphenyl)-3-methylindol-1-yl]hexane which reacted in DMF with K2PtCl4 in 5:2 DMF-H2O with light exclusion to give I [R1 = 5-OH, R2 = R5 = R6 = H, R3 = Me, R4 = 4-OH, Alk = (CH2)6, AB = NHCH2CH2NH2, X = Cl]. I, at 20 mg/kg (mice), reduced tumor wt. by 89%. An injection formulation contained 100 mg III in 10 mg of 1:1 polyethylene glycol 400/0.9% of NaCl.
|Additional information (public):||CAN 109:92780 27-11 Heterocyclic Compounds (One Hetero Atom) Patent 19880414 115084-37-2P; 115084-38-3P; 115084-39-4P; 115084-41-8P; 116041-07-7P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and reaction of, in synthesis of antitumor platinum complex); 115084-42-9P; 116041-09-9P; 116041-10-2P; 116041-11-3P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. and reaction of, in synthesis of antitumor platinum complex with indole deriv.); 115140-97-1P; 115140-98-2P; 115140-99-3P; 115141-00-9P; 115141-01-0P; 115141-02-1P; 115160-74-2P; 115160-75-3P; 115357-82-9P; 115357-83-0P; 115357-84-1P; 115357-85-2P; 115357-86-3P; 115357-87-4P; 115357-88-5P; 115357-89-6P; 115357-90-9P; 115362-88-4P; 115378-88-6P Role: BAC (Biological activity or effector, except adverse), BSU (Biological study, unclassified), SPN (Synthetic preparation), THU (Therapeutic use), BIOL (Biological study), PREP (Preparation), USES (Uses) (prepn. of, as antitumor agent); 107-15-3 (1,2-Ethanediamine); 109-77-3 (Malononitrile); 629-03-8 (1,6-Dibromohexane); 91444-18-7 Role: RCT (Reactant), RACT (Reactant or reagent) (reaction of, in synthesis of antitumor platinum complex); 1074-82-4 (Phthalimide potassium); 116041-08-8; 116041-12-4 Role: RCT (Reactant), RACT (Reactant or reagent) (reaction of, in synthesis of antitumor platinum complex of indole derivs.) A1 DE 86-3633673 19861003|
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Retired Professors > Prof. Schönenberger|
|Keywords:||Neoplasm inhibitors (platinum complex of phenylindoles) tumor inhibitor indole platinum complex prepn|
|Subjects:||500 Science > 540 Chemistry & allied sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||15 Nov 2010 15:32|
|Last Modified:||15 Nov 2010 15:32|