Configurational stability of bisindolylmaleimide cyclophanes: from conformers to the first configurationally stable, atropisomeric bisindolylmaleimides.

2.50
Hdl Handle:
http://hdl.handle.net/11287/619058
Title:
Configurational stability of bisindolylmaleimide cyclophanes: from conformers to the first configurationally stable, atropisomeric bisindolylmaleimides.
Authors:
Barrett, S.; Bartlett, S.; Bolt, Amanda H. ( 0000-0003-4303-2718 ) ; Ironmonger, A.; Joce, C.; Nelson, A.; Woodhall, T.
Abstract:
The bisindolylmaleimides are selective protein kinase inhibitors that can adopt two limiting diastereomeric (syn and anti) conformations. The configurational stability of a range of substituted and macrocyclic bisindolylmaleimides was investigated by using appropriate techniques. With unconstrained bisindolylmaleimides, the size of the 2-indolyl substituents was found to affect configurational stability, though not sufficiently to allow atropisomeric bisindolylmaleimides to be obtained. However, with a tether between the two indole nitrogen atoms in place, the steric effect of 2-indolyl substituents was greatly exaggerated, leading to large differences in configurational stability. The rate of interconversion of the syn and anti conformers varied by over twenty orders of magnitude through substitution of a bisindolylmaleimide ring system, which was constrained within a macrocyclic ring. Indeed, the first examples of configurationally stable atropisomeric bisindolylmaleimides are reported; the half-life for epimerisation of these compounds at room temperature was estimated to be >10(7) years.
Citation:
Configurational stability of bisindolylmaleimide cyclophanes: from conformers to the first configurationally stable, atropisomeric bisindolylmaleimides. 2005, 11 (21):6277-85 Chemistry
Publisher:
Wiley
Journal:
Chemistry (Weinheim an der Bergstrasse, Germany)
Issue Date:
21-Oct-2005
URI:
http://hdl.handle.net/11287/619058
DOI:
10.1002/chem.200500520
PubMed ID:
16075446
Additional Links:
http://onlinelibrary.wiley.com/doi/10.1002/chem.200500520/full?scrollTo=references
Note:
This article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site.
Type:
Research Support, Non-U.S. Gov't
Language:
en
ISSN:
0947-6539
Appears in Collections:
pre-2014 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorBarrett, S.en
dc.contributor.authorBartlett, S.en
dc.contributor.authorBolt, Amanda H.en
dc.contributor.authorIronmonger, A.en
dc.contributor.authorJoce, C.en
dc.contributor.authorNelson, A.en
dc.contributor.authorWoodhall, T.en
dc.date.accessioned2016-08-30T10:46:48Z-
dc.date.available2016-08-30T10:46:48Z-
dc.date.issued2005-10-21-
dc.identifier.citationConfigurational stability of bisindolylmaleimide cyclophanes: from conformers to the first configurationally stable, atropisomeric bisindolylmaleimides. 2005, 11 (21):6277-85 Chemistryen
dc.identifier.issn0947-6539-
dc.identifier.pmid16075446-
dc.identifier.doi10.1002/chem.200500520-
dc.identifier.urihttp://hdl.handle.net/11287/619058-
dc.description.abstractThe bisindolylmaleimides are selective protein kinase inhibitors that can adopt two limiting diastereomeric (syn and anti) conformations. The configurational stability of a range of substituted and macrocyclic bisindolylmaleimides was investigated by using appropriate techniques. With unconstrained bisindolylmaleimides, the size of the 2-indolyl substituents was found to affect configurational stability, though not sufficiently to allow atropisomeric bisindolylmaleimides to be obtained. However, with a tether between the two indole nitrogen atoms in place, the steric effect of 2-indolyl substituents was greatly exaggerated, leading to large differences in configurational stability. The rate of interconversion of the syn and anti conformers varied by over twenty orders of magnitude through substitution of a bisindolylmaleimide ring system, which was constrained within a macrocyclic ring. Indeed, the first examples of configurationally stable atropisomeric bisindolylmaleimides are reported; the half-life for epimerisation of these compounds at room temperature was estimated to be >10(7) years.en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1002/chem.200500520/full?scrollTo=referencesen
dc.rightsArchived with thanks to Chemistry (Weinheim an der Bergstrasse, Germany)en
dc.subjectWessex Classification Subject Headings::Biochemistryen
dc.titleConfigurational stability of bisindolylmaleimide cyclophanes: from conformers to the first configurationally stable, atropisomeric bisindolylmaleimides.en
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalChemistry (Weinheim an der Bergstrasse, Germany)en
dc.description.noteThis article is freely available via Open Access. Click on the 'Additional Link' above to access the full-text from the publisher's site.en
dc.type.versionPublisheden

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