35989-93-6

Upstream product

• 4927-55-3 1,2-bis(3,4-dimethoxyphenyl)ethanone 
• 75-05-8 acetonitrile 
• 10313-60-7 3,4-dimethoxyphenylacetyl chloride 
• 91-16-7 1,2-dimethoxybenzene 
• 91486-63-4 1-Methyl-3-(3,4-dimethoxyphenyl)-6,7-dimethoxytetrahydroisoquinoline 

Downstream Products

• 180077-32-1 6,7-Dihydroxy-1-methyl-3-(3,4-dihydroxyphenyl)isoquinoline 

Relevant academic research and scientific papers

Coralyne analogs as topoisomerase inhibitors

The present invention provides protoberberine alkaloid derivatives useful as anticancer agents, and methods of use thereof. The invention also provides protoberberine derivatives useful as topoisomerase inhibitors. The invention further provides coralyne and nitidine derivatives which are topoisomerase I-targeted therapeutics effective against camptothecin resistant cancer cells, and are especially effective against CNS tumors.

Coralyne and related compounds as mammalian topoisomerase I and topoisomerase II poisons

DNA topoisomerases are nuclear enzymes responsible for modifying the topological state of DNA. The development of agents capable of poisoning topoisomerases has proved to be an attractive approach in the search for novel cancer chemotherapeutics. Coralyne, an antileukemic alkaloid, has appreciable structural similarity to the potent topoisomerase I and II poison, nitidine. Analogues of coralyne were synthesized and evaluated for their activity as topoisomerase I and topoisomerase II poisons. These analogues were also evaluated for cytotoxicity in the human lymphoblast cell line, RPMI 8402, and its camptothecin-resistant variant, CPT-K5. The pharmacological activity of these analogues exhibited a strong dependence on the substitution pattern and the nature of substituents. Several 1- benzylisoquinolines and 3-phenylisoquinolines were also synthesized. These compounds, which incorporate only a portion of the ring structure of coralyne, were evaluated as topoisomerase poisons and for cytotoxicity. These structure-activity studies indicate that the structural rigidity associated with the coralyne ring system may be critical for pharmacological activity. The presence of a 3,4-methylenedioxy substituent on these coralyne analogues was generally associated with enhanced activity as a topoisomerase poison. 5,6-Dihydro-3,4-methylenedioxy-10,11-dimethoxydibenzo[a,g]quinolizinium chloride was the most potent topoisomerase I poison among the coralyne analogues evaluated, having similar activity to camptothecin. This analogues also possessed exceptional potency as a topoisomerase II poison. Despite the pronounced activity of several of these coralyne derivatives as topoisomerase I poisons, mine of these compounds had cytotoxic activity similar to camptothecin. Possible differences in cellular absorption between these coralyne analogs, which possess a quaternary ammonium group, and camptothecin may be responsible for the differences observed in their relative cytotoxicity.

A SIMPLE DIRECT APPROACH TO 1-SUBSTITUTED 3-ARYLISOQUINOLINES FROM DEOXYBENZOINS AND NITRILES

A new one-pot synthesis of 3-arylisoquinolines was accomplished by reaction of deoxybenzoins with an excess of nitriles and phosphorus pentoxide at room temperature.The usefulness of this synthesis was demonstrated by the facile preparation of 1-alkyl, 1-

Dehydrogenation Reactions of 1-Substituted-3-Aryltetrahydroisoquinoline Derivatives

The 1-substituted-3-aryltetrahydroisoquinolines I have been converted into the corresponding 3,4-dihydro- or isoquinoline derivatives by treatment with several oxidizing agents: iodine in ethanol, palladium on carbon, DDQ and Fremy's salt.The oxidation re

REACTION OF 1-ALKYL-3-ARYL-BENZOPYRYLIUM SALTS WITH AMMONIA

It has been previously shown that 2-benzopyrylium salts reacts with ammonia under various conditions to give either isoquinolines or their precursors - 3-hydroxy-3,4-dihydroisoquinolines or 1,5-dicarbonyl compounds - i.e., only one reaction pathway was es