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Optimization of the indenone ring of indenoisoquinoline topoisomerase I inhibitors.
J Med Chem. 2007 Sep 06; 50(18):4388-404.JM

Abstract

Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary biological evaluation, a more focused series of inhibitors was prepared utilizing a 2,3-dimethoxy-substituted isoquinoline ring. The results of the two series indicate the existence of superior functional groups such as methoxy, fluorine, and cyano for the indenoisoquinoline 9-position. Interestingly, these functional groups coincide with established structure-activity relationships for the 11-position of camptothecin.

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Authors+Show Affiliations

Morrell A
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA.
Placzek M
No affiliation info available
Parmley S
No affiliation info available
Grella B
No affiliation info available
Antony S
No affiliation info available
Pommier Y
No affiliation info available
Cushman M
No affiliation info available

MeSH

Antineoplastic AgentsCell Line, TumorCrystallography, X-RayDNA CleavageDNA Topoisomerases, Type IDrug Screening Assays, AntitumorHumansIndenesIsoquinolinesModels, MolecularMolecular StructureStructure-Activity RelationshipTopoisomerase I Inhibitors

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17676830

Citation

Morrell, Andrew, et al. "Optimization of the Indenone Ring of Indenoisoquinoline Topoisomerase I Inhibitors." Journal of Medicinal Chemistry, vol. 50, no. 18, 2007, pp. 4388-404.
Morrell A, Placzek M, Parmley S, et al. Optimization of the indenone ring of indenoisoquinoline topoisomerase I inhibitors. J Med Chem. 2007;50(18):4388-404.
Morrell, A., Placzek, M., Parmley, S., Grella, B., Antony, S., Pommier, Y., & Cushman, M. (2007). Optimization of the indenone ring of indenoisoquinoline topoisomerase I inhibitors. Journal of Medicinal Chemistry, 50(18), 4388-404.
Morrell A, et al. Optimization of the Indenone Ring of Indenoisoquinoline Topoisomerase I Inhibitors. J Med Chem. 2007 Sep 6;50(18):4388-404. PubMed PMID: 17676830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Optimization of the indenone ring of indenoisoquinoline topoisomerase I inhibitors. AU - Morrell,Andrew, AU - Placzek,Michael, AU - Parmley,Seth, AU - Grella,Brian, AU - Antony,Smitha, AU - Pommier,Yves, AU - Cushman,Mark, Y1 - 2007/08/04/ PY - 2007/8/7/pubmed PY - 2007/11/2/medline PY - 2007/8/7/entrez SP - 4388 EP - 404 JF - Journal of medicinal chemistry JO - J Med Chem VL - 50 IS - 18 N2 - Two series of indenoisoquinoline topoisomerase I inhibitors have been prepared to investigate optimal substituents on the indenone ring at the 9-position. The more exhaustive series was prepared using a nitrated isoquinoline ring that has been previously demonstrated to enhance biological activity. After preliminary biological evaluation, a more focused series of inhibitors was prepared utilizing a 2,3-dimethoxy-substituted isoquinoline ring. The results of the two series indicate the existence of superior functional groups such as methoxy, fluorine, and cyano for the indenoisoquinoline 9-position. Interestingly, these functional groups coincide with established structure-activity relationships for the 11-position of camptothecin. SN - 0022-2623 UR - https://www.unboundmedicine.com/medline/citation/17676830/Optimization_of_the_indenone_ring_of_indenoisoquinoline_topoisomerase_I_inhibitors_ L2 - https://doi.org/10.1021/jm070307+ DB - PRIME DP - Unbound Medicine ER -