uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Preparation of imidazolyl-pyrimidine derivatives as GSK3 inhibitors.
Show others and affiliations
2008 (English)Patent (Other (popular science, discussion, etc.))Text
Abstract [en]

Title compds. I [R1 = sulfamoyl, carbamoyl or -R5-R6 and N linked (un)substituted 4- to 7-membered satd. ring which optionally contains an addnl. N, O or S; R5 = O, C(O), C(O)O, C(O)NH, etc., R6 = (un)substituted alkyl, carbocyclyl or heterocyclyl; at least one of X1, X2, X3 and X4 = N, the other three independently = N or C(R9), wherein R9 = H, halo, CN, OH, NH2, alkyl or alkoxy; provided that not more than two of X1, X2, X3 or X4 = N; R2 = halo or CN; R3 = Me, (un)substituted 3-tetrahydropyranyl or 4-tetrahydropyranyl; R4 = H, halo, CN or (un)substituted alkyl], and their pharmaceutically acceptable salts, are prepd. and disclosed as glycogen synthase kinase 3 (GSK3) inhibitors. Thus, e.g., II was prepd. by amidation of 3,5-dichloro-2-pyridinecarboxylic acid with piperidine followed by coupling reaction with 5-fluoro-4-[2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl]pyrimidin-2-amine, which was prepd. starting from 5-methyl-4-aminoisoxazole and tetrahydro-2H-pyran-4-one in 5 steps. All the exemplar compds. were evaluated for their GSK3 inhibitory activity in GSK3 inhibition assays with typical Ki values ranging from 0.001 to 10,000 nM. For instance, II exhibited a Ki value of 7 nM. As inhibitors of GSK3, I should prove useful in treatment and prevention of GSK3 assocd. diseases including Alzheimer's disease. [on SciFinder(R)]

Place, publisher, year, edition, pages
AstraZeneca AB, Swed. . , 2008. no WO2008002244A2
Keyword [en]
pyrimidine imidazolyl prepn GSK3 inhibitor Alzheimer disease treatment
National Category
Medicinal Chemistry
URN: urn:nbn:se:uu:diva-270235OAI: oai:DiVA.org:uu-270235DiVA: diva2:888179

CAPLUS AN 2008:9934(Patent)

Available from: 2015-12-22 Created: 2015-12-22 Last updated: 2015-12-22

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Yngve, Ulrika.
Medicinal Chemistry

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 52 hits
ReferencesLink to record
Permanent link

Direct link