Nonpeptide analogues

N-deprotection Removal of N-protecting groups, nonpeptidomimetics Nonpeptide analogues, usually small molecules, nonpolar Hydrophobic molecules that are poorly soluble in water, oligopeptide A few amino acids joined by peptide bonds. 

ADH antagonists, including nonpeptide analogues that may be taken orally, have been developed with specificity for each of the receptor types. In the future, those that block Vj receptors may be useful in treating hypertension, and those that block Vj receptors may be useful in any condition of excessive water retention or hyponatremia, for which so far there is no satisfactory therapeutic treatment. 

Table 19. Tricyclic Nonpeptide FTIs 8-Chlorobenzocycloheptapyridine Substituted Piperazine and Piperidine Analogues...

Both peptide and nonpeptide 5-opioid antagonists have been developed. The nonpeptide 6-antagonist naltrindole and its analogues are described in Chapter 9 of this volume. In the present chapter, the development of opioid peptide-derived 6-antagonists, inverse 6-agonists, and mixed p-agonist/6-antagonists is reviewed. 

Tautomerization is a relatively common feature of drug molecules that is equally amenable to simple analysis using chemical shifts or coupling constants as probes. This was recently demonstrated in a study of some nonpeptide endothelin analogues.45... 

Nonpeptide analogues of cj-conotoxin MVIIA have demonstrated comparable N-type VSCC interaction efficiency. A better understanding of the pharmacophore of ziconotide may lead to the development of truncated peptides or peptidomimetic analogues. ... 

Due to their high selectivity, DER and DEL were the basis for an extensive structure activity relationship study aimed to understand the essential requisites of p. and 8 activity. More than 200 analogues of DER and DEL C were synthesized, and the role of each amino acid in binding to p and 8 receptors and bioactivity was defined [21-31]. New synthetic products were prepared such as oxymorphindole and related derivatives [32], and (+)-4-[(alfa R)-alfa-((2S,5R)-4-allyl-2.5-dimethyl-l-piperazin-yl)-3-methoxy-benzyl]-N, diethylbenzamide [33]. These products are under investigation for their clinical relevance and provide potential nonpeptide ligands for studies on delta-opioid-receptor. 

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