Linked Life Data

10508447

Source:http://linkedlifedata.com/resource/pubmed/id/10508447

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
1999-10-21
pubmed:abstractText
Syntheses of several carbamate analogues of 2, 5-bis(4-amidinophenyl)furan (1) under mild conditions and their evaluation as prodrugs against Pneumocystis carinii pneumonia (PCP) in an immunosuppressed rat model are described. Thus, nine new bis-carbamates: methoxycarbonyl (2), 2,2,2-trichloroethoxycarbonyl (3), ethylthiocarbonyl (4), benzyloxycarbonyl (5), (4-methyl-2-oxo-1, 3-dioxol-4-en-5-yl)methoxycarbonyl (6), phenoxycarbonyl (7), 4-fluorophenoxycarbonyl (8), 4-methoxyphenoxycarbonyl (9), and (1-acetoxy)ethoxycarbonyl (10) and a bis-carbonate ethoxycarbonyloxy (11) of the bis-amidine 1 have been synthesized and evaluated. The in vivo results show that the 4-fluorophenyl carbamate 8 and the 4-methoxyphenyl carbamate 9 in this series had the best anti-PCP activity by both intravenous and oral administration at a dosage level of 22 mol and 33 micromol/kg/day, respectively. Compounds 3-7 were also more active than the parent drug (1) on oral administration. The acute toxicity usually exhibited by the parent amidine 1 at a dosage level of 22 micromol/kg/day on intravenous administration has been significantly reduced by the prodrug modifications, with the exception of compound 10 which exhibited some toxicity. This report also describes the synthesis of several aryl-alkyl and aryl-aryl carbonates (12-14, 16-23) as efficient reagents for the preparation of carbamate derivatives from bis-arylamidines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3994-4000
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Prodrugs for amidines: synthesis and anti-Pneumocystis carinii activity of carbamates of 2,5-bis(4-amidinophenyl)furan.
pubmed:affiliation
Department of Chemistry and Center for Biotechnology and Drug Design, Georgia State University, Atlanta, Georgia 30303, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't