Linked Life Data

9755719

Source:http://linkedlifedata.com/resource/pubmed/id/9755719

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1998-10-19
pubmed:abstractText
Tirapazamine (1,2,4-benzotriazin-3-amine 1,4-dioxide, SR 4233, WIN 59075) is the lead compound representing this class of anticancer drugs. It is also the first compound to be introduced in the clinic as a pure bioreductive cytotoxic agent. Tirapazamine represents a completely novel approach to the treatment of solid tumors and has generated considerable interest, with research being carried out on all aspects of the its anticancer activity. Phase III trials of tirapazamine in combination with cisplatin (cDDP) have recently been concluded, and phase II trials of triapazamine in combination with irradiation are presently being performed. We developed a drug discovery program into this class of compounds designed to produce derivatives with improved in vivo activity against solid tumors. Based on the hypothesis that these compounds require bioreductive activation for antitumor activity, the research was primarily directed at producing analogues with greater electron affinity and improved aqueous solubility. The in vitro and in vivo data for a variety of structural analogues clearly show that 1,2,4-benzotriazine 1,4-dioxides have considerable potential as anticancer agents. When their activity is compared directly with the activity observed for triapazamine, the most promising series of analogues appears to be the 3-alkyl-substituted derivatives, especially the 3-ethyl- and 3-(2'-methoxyethyl)-derivatives, SR 4895 and SR 4941 respectively.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0266-9536
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
575-92
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
1,2,4-Benzotriazine 1,4-dioxides. An important class of hypoxic cytotoxins with antitumor activity.
pubmed:affiliation
Pharmaceutical Discovery Division, SRI International, Menlo Park, CA 94025, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't