[Abstract]2024 May 9:73:103187
A method of preventing weakness in a patient with Parkinson's disease or of improving or restoring muscle strength of a patient with Parkinson's disease, comprising the step of administering to said patient an amount of one or more hepatocyte growth factor mimics sufficient to prevent, improve or restore to normal said muscle strength, said one or more hepatocyte growth factor mimics having a general structural formula 1 2 3 where R] is one of an N-acyl group, a substituted or unsubstiruted phenyl, a norleucine group, and an amino acid selected from tyrosine, phenylalanine, aspartic acid, arginine, isoleucine, serine, histidine, glycine, cysteine, methionine, tryptophan, lysine norvaline, ornithine, and s-benzyl cysteine
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The structure of the IRAP ( vide infra ( The metathesis reaction was applied to obtain a series of macrocyclic compounds, devoid of the reactive disulfide function and with the potential to become oral bioavailable and more metabolically stable ( 28 exhibited a Ki value of 4.1 nM and the corresponding analogue with a saturated double bond, compound 29 , a Ki value of 25 nM, demonstrating that a proper constrain of flexibility of the ring system, alternatively an electron density in the center of the lipophilic bridge between amino acid residues in positions 1 and 3 is favorable for affinity to IRAP (Figure 7)
