Linked Life Data

874955

Source:http://linkedlifedata.com/resource/pubmed/id/874955

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1977-8-25
pubmed:abstractText
Treatment of N-acylproline derivatives, 2, with acetic anhydride--dimethyl acetylenedicarboxylate (DMAD) gave 5-substituted derivatives of dimethyl 2,3-dihydro-1H-pyrrolizine-6,7-dicarboxylate (5). The reaction proceeds via a 1,3-dipolar addition of DMAD with the mesoionic oxazalone intermediate 3, generated in situ, with concomitant elimination of carbon dioxide. Reduction of 5 gave the diols 6 which upon subsequent acylation gave 1. The bis(N-methylcarbamate) 1d and the diacetate li show a modest level of in vivo antileukemia activity in the L1210 assay. A majority of the diesters, 1, showed significant antileukemic activity in the in vivo P-388 assay. The bis(carbamate) 1d afforded "cures" at dose levels as low as 12.5 mg/kg; 1 q showed potent activity at doses as low as 0.78 mg/kg. Several other compounds showed potent activity against P-388 over a greater than fourfold dose range with no acute toxicity. Half-lives for several diacetate derivatives of 1 were determined for aqueous Me2SO solutions. The preparation of 7 and 8 shows that 1 may react by O-alkyl ester cleavage.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
812-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1977
pubmed:articleTitle
Synthesis and antileukemic activity of 5-substituted 2,3-dihydro-6,7-bis(hydroxymethyl)-1H-pyrrolizine diesters.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S.