[Synthesis of hydrazino alcohols with anti-inflammatory activity].
Two-step transformations (N-nitrosation and subsequent LiAlH4 reduction) of alicyclic or acyclic amines and 1,2-amino alcohols containing a secondary amino group were applied to prepare novel N1-substituted hydrazines and hydrazino alcohols with wide structural diversity. Methods for the synthesis of certain enantiopure hydrazino alcohols were also developed. The prepared compounds specifically inhibited Vascular Adhesion Protein-1 (VAP-1), a human endothelial cell adhesion molecule with a well-documented role in inflammation. VAP-1 is a semicarbazide-sensitive amine oxidase, activity of which has been demonstrated to play a role in VAP-1 induced inflammation. Some of the hydrazino alcohols obtained reduced the clinical symptoms of inflammation in experimental arthritis in rodents and appear to be potential novel anti-inflammatory drugs.
Lázár
Laszló
L
Szegedi Tudományegyetem, Gyógyszerkémiai Intézet, Szeged, Eötvös u. 6. - 6720.
Szakonyi
Zsolt
Z
Forró
Eniko
E
Palkó
Márta
M
Zalán
Zita
Z
Szatmári
István
I
Fülöp
Ferenc
F
D000438:Alcohols / Q000138:chemical synthesis*; D006631:Amine Oxidase (Copper-Containing) / Q000032:analysis / Q000502:physiology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology; D015195:Drug Design; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis*; D007249:Inflammation
D000438:Alcohols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D006834:Hydrazines; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)