Synthesis, structure and tumour necrosis factor-alpha production-enhancing properties of novel adamantylamino heterocyclic derivatives.
The synthesis of several adamantylated aminoheterocycles is reported. The attack of the adamantyl cation formed from 1-adamantanol in refluxing trifluoroacetic acid or induced by microwave irradiation provides adamantylamino-derivatives of respective heterocycles. Adamantylated heterocycles enhance the induction of tumour necrosis factor alpha (TNF-alpha) in genetically modified murine melanoma cells transduced with the gene for human TNF-alpha. Of the studied collection of adamantylated compounds, the most biologically active are 2-adamantylamino-6-methylpyridine and 2-adamantylamino4-methylpyrimidine. The crystal structure of 2-adamantylamino-6-methylpyridine is reported.
Mauri
J K
JK
Drug Institute, Warsaw, Poland. maurin@urania.il.waw.pl
Lasek
W
W
Górska
A
A
Switaj
T
T
Wamil
M
M
Młynarczuk
I
I
Kazimierczuk
Z
Z
D000218:Adamantane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000277:Adjuvants, Pharmaceutic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D014409:Tumor Necrosis Factor-alpha; D000218:Adamantane