Overview

Katritzky, Alan R.; Ramsden, Christopher A.; Joule, J. A.; Zhdankin, Viktor V.

doi:10.1016/b978-0-08-095843-9.00002-1

Cited by 92 publications

(130 citation statements)

References 0 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…8 ) could be controlled by regioselective reactions of carbonyl groups attached to C-2 and C-4 as opposed to C-3 of the pyridine ring system. 29–31 This would ultimately dictate the locations of the nitrogen in the final products.…”

Section: Chemistrymentioning

confidence: 99%

Investigation of the Structure–Activity Relationships of Aza-A-Ring Indenoisoquinoline Topoisomerase I Poisons

Beck

Reddy

et al. 2016

J. Med. Chem.

View full text Add to dashboard Cite

Several indenoisoquinolines have shown promise as anticancer agents in clinical trials. Incorporation of a nitrogen atom into the indenoisoquinoline scaffold offers the possibility of favorably modulating ligand-binding site interactions, physicochemical properties, and biological activities. Four series of aza-A-ring indenoisoquinolines were synthesized in which the nitrogen atom was systematically rotated to all four possible locations. The resulting compounds were tested to establish the optimal nitrogen position for topoisomerase IB (Top1) enzyme poisoning activity and cytotoxicity to human cancer cells. The 4-aza compounds were the most likely to yield derivatives with high Top1 inhibitory activity. However, the cytotoxicity was more complicated, since the potency was influenced strongly by the side chains on the lactam nitrogen. The most cytotoxic azaindenoisoquinolines 45 and 46 had nitrogen in the 2- or 3-positions and a 3′-dimethylaminopropyl side chain, and they had MGM GI50 values that were slightly better than the corresponding indenoisoquinoline 64.

show abstract

Section: Chemistrymentioning

confidence: 99%

Investigation of the Structure–Activity Relationships of Aza-A-Ring Indenoisoquinoline Topoisomerase I Poisons

Beck

Reddy

et al. 2016

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

“…1 Although heterocycles devoid of chiral centers can be effective therapeutics (e.g., tyrosine kinase inhibitors), the selective disruption of more complex interactions (e.g., protein–protein interactions) have increased attention on the expansion and tailoring of molecular space, leading to drug candidates with complex structures containing several chiral centers. 2 Chiral auxiliaries, kinetic resolution, and hydrogenation methods are well-established in industrial settings and continue to be successfully applied to the large scale preparations of APIs.…”

Section: Introductionmentioning

confidence: 99%

Development of an Intermittent-Flow Enantioselective Aza-Henry Reaction Using an Arylnitromethane and Homogeneous Brønsted Acid–Base Catalyst with Recycle

Tsukanov

Johnson

May

et al. 2016

Org. Process Res. Dev.

View full text Add to dashboard Cite

A stereoselective aza-Henry reaction between an arylnitromethane and Boc-protected aryl aldimine using a homogeneous Brønsted acid–base catalyst was translated from batch format to an automated intermittent-flow process. This work demonstrates the advantages of a novel intermittent-flow setup with product crystallization and slow reagent addition which is not amenable to the standard continuous equipment: plug flow tube reactor (PFR) or continuous stirred tank reactor (CSTR). A significant benefit of this strategy was the integration of an organocatalytic enantioselective reaction with straightforward product separation, including recycle of the catalyst, resulting in increased intensity of the process by maintaining high catalyst concentration in the reactor. A continuous campaign confirmed that these conditions could effectively provide high throughput of material using an automated system while maintaining high selectivity, thereby addressing nitroalkane safety and minimizing catalyst usage.

show abstract

“…From the structure of complex 5 it is evident that compound 2 is indeed a selenoether and not a diselenide. The lengths of C–C and C–N bonds in pyrazole rings are within the usual range [21]. The lengths of Se–C bonds (1.95-1.96 Å) are also common for acyclic selenoethers [22].…”

Section: Resultsmentioning

confidence: 99%