Linked Life Data

7783117

Source:http://linkedlifedata.com/resource/pubmed/id/7783117

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1995-7-18
pubmed:abstractText
Reactions of the [D-serine]8-cyclosporin (2) with a series of alkylating agents under phase transfer conditions gave the alkylated products 3-6. Alkylations of 2 with hindered esters of bromoacetate gave the crystalline esters 7 and 8. Hydrolysis under basic conditions gave the acid 10. Reduction of ester 8 led to a novel cyclosporin 11. This was transformed in two additional steps to 15. In a similar two-step sequence 17 was prepared from 15. From 2 and methyl 2-(bromomethyl)acrylate product 20 was obtained. Alkylation of 2 with 49 followed by deprotection yielded 24. The linear isomer 27 was prepared. The 3-hydroxypropyl ether 30 was prepared in two steps from 28. The 4-hydroxybutyl ether 31 was accessible from 2 and 1,4-dibromobutane. The hydroxy group of 11 was converted to the tosylate 32. Base treatment of 32 led to the bicyclic [3(R)-morpholinecarboxylic acid]8-cyclosporin (39). The [2-ethoxy-5-morpholinecarboxylic acid]8-cyclosporin 40 was prepared via 36. Base treatment of the bromoacetate 37 gave the morpholinone derivative 41. [4(R)-Oxazolidinecarboxylic acid]8-cyclosporin (42) was obtained from 2 and methylene bromide. From 24 the tosylate 38 was prepared and cyclized to the hexahydrooxazepine derivative 43. [2(R)- Piperidinecarboxylic acid]8-cyclosporin (49) was prepared from 42 and 2(R)-piperidinecarboxylic acid 45 via 46-48. The bicyclic cyclosporin 39 was found to be about 3-4 times more active than cyclosporin A in our in vitro tests.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1853-64
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Preparation and in vitro activities of ethers of [D-serine]8-cyclosporin.
pubmed:affiliation
Sandoz Ltd., Basel, Switzerland.
pubmed:publicationType
Journal Article, Comparative Study