V

o 0 V0(02)cmaa

V0(02)2Ala-His

V0(02)2Ala-His

Figure 8.1 (Continued)

Figure 8.1, successfully passed the phase I clinical test.19 Picolinic acid and its derivatives with N,O coordination,25 and dipicolinate with O,N,O coordination are also promising ligands, the latter having been successfully applied orally to diabetic cats.26 Surprisingly, N,S-coordinated complexes have also been found to be efficient in in vivo tests,22 but some of them could not be detected in solution when the components were mixed in a test tube. This may mean that if these complexes are dissolved in water, they rapidly decompose and cannot keep their integrity in the stomach or intestine, where they are expected to be absorbed. The V(V) hydroxylamido complex, an excellent inhibitor of protein tyrosine phosphatase,27 is an efficient insulin mimetic. In order to be effective,19 a vanadium compound should fulfil a number of preconditions. Among others, hydrophilicity and lipophilicity should be balanced by an appropriate design of the ligand in order to allow absorption and transport in the bloodstream. It should have a low molecular mass (LMM) in order to cross the cell membrane easily. Of course, an additional demand is low toxicity.

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