Nonpeptidic

Docking also provided insight into the 3D hydrophobic requirements for binding of nonpeptide molecules in the SH2 domain of ppGOsrc at ARIAD Pharmaceuticals [92]. 

Flow chart showing the design of novel orally active HIV-1 protease inhibitor. (Figure adapted from Lam P K ]adhav, C E Eyermann, C N Hodge, Y Ru, L T Bacheler, ] L Meek, M ] Otto, M M Rayner, Y N V /ong, ang, P C Weber, D A Jackson, T R Sharpe and S Erickson-Viitanen 1994. Rational Design of Potent, able. Nonpeptide Cyclic Ureas as HIV Protease Inhibitors. Science 263 380-384.)... 

Other potential oxytocia antagonists are being developed using leads from naturally occurring, nonpeptide stmctures, such as an extract from Streptomjces (48). A selective nonpeptide vasopressin receptor antagonist also has been found (49). 

The CCK system shares one property with the opioid system, ie, the existence of selective nonpeptide antagonists. These include aspedicine, a natural benzodiazepine (136), and Devazepide (L-364,718 MK-329) (137). Selective, potent peptide antagonists for CCK, eg, Cl-988 and PD 134308, have been developed that maybe useful as anxiolytics and as dmgs which increase the analgesic effect of morphine but at the same time prevent morphine tolerance (138) (see Hypnotics, sedatives, anticonvulsants, and anxiolytics). 

Fig. 4. Structures of several nonpeptide opioid agonists, (a) morphine, (c) BW373U86, (e) U50488 and antagonists, (b) naloxone, (d) naltrindole, and (f)...

This amide, readily formed from an amine and the anhydride, is readily cleaved by penicillin acylase (pH 8.1, A -methylpyrrolidone, 65-95% yield). This depro-tection procedure works on peptides as well as on nonpeptide substrates. 

This amide, readily formed from an amine and the anhydride or enzymatically using penicillin amidase, is readily cleaved by penicillin acylase (pH 8.1, A -methylpyrrolidone, 65-95% yield). This deprotection procedure works on peptides, phosphorylated peptides, and oligonucleotides, as well as on nonpeptide substrates. The deprotection of racemic phenylacetamides with penicillin acylase can result in enantiomer enrichment of the cleaved amine and the remaining amide. An immobilized form of penicillin G acylase has been developed. ... 

G. Jung (ed.), Combinatorial Peptide and Nonpeptide Libraries. A Handbook, VCH, Weinbeim, 1996. 

Today, 3D databases, which provide the means for storing and searching for 3D information of compounds, are proven to be useful tools in drug discovery programs. This is well exemplified with the recent discovery of novel nonpeptide HIV-1 protease inhibitors using pharmacophore searches of the National Cancer Institute 3D structural database [13-15]. 

A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc. Natl. AcadSci. USA 96 5698-5703. 

More than 50 endogenous and exogenous inhibitors of the calpains have been described as either transition-state reversible or irreversible inhibitors. The first transition-state inhibitors were the peptide aldehydes (e.g., leupeptin). Using this compound, new ones were synthesized that exhibited improved membrane permeability and calpain specificity (e.g., calpeptin). Other groups of inhibitors have since been discovered a-dicarbonyls (originally developed as serine protease inhibitors), nonpeptide quinolinecarboxamides,... 

Inhibition of V2 vasopressin receptors causes an increase in urine volume primarily by reducing the re-absoiption of water along the collecting duct, an aquaretic effect that is fundamentally different from the natriuretic actions discussed so far. Nevertheless, some of the conditions calling for the use of natriuretic intervention are identical to those in which the administration of a new class of orally active nonpeptide V2 antagonists may be useful (tolvaptan, lixivaptan, and others). 

Significant progress has been made in the development of nonpeptidic ligands for the GAL3 receptor (Fig. 1). 3-Arylimino-2-indolones including SNAP 37889 and SNAP 398299 were shown by Swanson... 

Galanin Receptors. Figure 1 Nonpeptide antagonists forGALI (top) and GAL3 (bottom). 

SR 48692 Nonpeptide antagonist at NTS1 agonist at NTS2 Inhibition of tumor growth drug addiction treatment... 

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