Total synthesis and biological properties of novel antineoplastic (chloromethyl)furanoindolines: an asymmetric hydroboration mediated synthesis of the alkylation subunits
| Autor: | Hamideh Zarrinmayeh, Gilbert S. Staten, P. Marder, Michael M. Spees, Johnson David Arthur, Dale L. Boger, Fariborz Mohamadi, Julia K. Kipka |
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| Rok vydání: | 1994 |
| Předmět: |
Boron Compounds
Indoles Lung Neoplasms Alkylation Cyclohexanecarboxylic Acids Stereochemistry Molecular Sequence Data Mice Nude Antineoplastic Agents Leucomycins Acylation Duocarmycins Mice Drug Discovery Cyclohexenes Tumor Cells Cultured Animals Humans Furans Benzofurans Bicyclic molecule Base Sequence Chemistry Enantioselective synthesis Total synthesis DNA Hydroboration DNA Alkylation Adozelesin Carcinoma Squamous Cell Molecular Medicine Female Drug Screening Assays Antitumor |
| Zdroj: | Journal of medicinal chemistry. 37(2) |
| ISSN: | 0022-2623 |
| Popis: | 1,2-Dihydro-1-(chloromethyl)-5-hydroxy-8-methyl-3H-furano[3,2-e]in dole (CFI) as a novel replacement of the cyclopropylpyrroloindoline (CPI) alkylation subunit of CC-1065, U-71184, and U-73975 (adozelesin) has been synthesized and incorporated into a series of efficacious antineoplastic agents. A partial solution to an asymmetric synthesis of the CFI alkylation subunit has been achieved by the implementation of an asymmetric hydroboration reaction of an intermediate 3-methyleneindoline (13). Extension to the asymmetric synthesis of the CBI and CI alkylation subunits is presented. The demonstration and comparative study of the sequence-selective DNA alkylation properties of the CFI-based agents are detailed, and the preliminary in vitro and in vivo antineoplastic properties of these agents in the human epidermoid cell lung carcinoma (T222) are described. |
| Databáze: | OpenAIRE |
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