Linked Life Data

10411479

Source:http://linkedlifedata.com/resource/pubmed/id/10411479

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1999-8-2
pubmed:abstractText
A general synthetic approach to novel cryptophycin analogues 6 is described. N-Hydroxysuccinimide active ester 15, a key common intermediate, was converted to beta-epoxide 6 in three steps, via initial coupling with unprotected amino acid 9, followed by deprotection/macrolactamization of acyclic precursor 16, and final oxidation of styrene 7 to install the C7-C8 beta-epoxide. Cryptophycin styrenes 7 and beta-epoxides 6, bearing diverse side chains in fragment "B", were evaluated for cytotoxic activity. beta-Epoxides 6, in general, were significantly more potent than the corresponding alpha-epoxides 17 and styrenes 7. A benzyl side chain was required for potent activity, with beta-epoxide 6u, possessing a 3-Cl,4-(dimethylamino)benzyl moiety, as the most potent cytotoxic agent prepared, with an IC(50) = 54 pM, only 2-fold less than that of Cryptophycin-52 (3).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2588-603
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Novel cryptophycin antitumor agents: synthesis and cytotoxicity of fragment "B" analogues.
pubmed:affiliation
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA. patel@kinetixpharm.com
pubmed:publicationType
Journal Article