ABSTRACT
Unsymmetrical diamide libraries have been prepared by a general and versatile solid phase route, using diacid templates in combination with aromatic and aliphatic amines chosen with the help of statistical experimental design. The compounds were tested as potential inhibitors of osteoclast vacuolar ATPase.
Subject(s)
Amides/chemical synthesis , Amides/pharmacology , Bone Resorption/drug therapy , Adenosine Triphosphatases/antagonists & inhibitors , Animals , Chickens , Databases, Factual , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Osteoclasts/drug effects , Osteoclasts/enzymology , Templates, GeneticABSTRACT
(2R,3S,1'R)-3-(1-Hydroxy-2-phosphonoethyl)-2-piperidinecarboxyl ic acid 1 has been synthesized by two different methods. The NMDA receptor binding affinities (Ki values) are 74 nM for compound 1, and 64 nM for the corresponding ketone 2. The analgesic effects were evaluated using the mouse hot-plate test and the mouse formalin model. The ED50 values for the racemates of compounds 1 and 2, using the mouse hotplate and intrathecal injection, were 0.53 and 0.51 nmol, respectively.
