Nonpeptide agonists

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

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

Chang KJ, Rigdon GC, Howard JL, McNutt RW. A novel, potent and selective nonpeptidic delta opioid receptor agonist. J Pharmacol Exp Ther 1993 267 852-857. 

Calderon SN, Rothman RB, Porreca F, Flippen-Anderson JL, McNutt RW, Xu H, Smith LE, Bilsky EJ, Davis P, Rice KC. Probes for narcotic receptor mediated phenomena. 19. Synthesis of ( + )-4-[(aR)-a-((25,5R)-4-allyl-2,5-dimethyl-l -piperazinyl)-3-methoxybenzyl]-/V,/V-diethylbenzamide (SNC80) a highly selective, nonpeptide delta opioid receptor agonist. J Med Chem 1994 37 2125-2128. 

Nonpeptide Agonists Bind in the Deep Part of the Main Ligand-Binding... 

Nonpeptide Antagonists May Bind Rather Differently from the Agonist.103... 

Not many nonpeptide agonists are yet available, but such compounds have been described — for example, in the angiotensin, CCK, and opioid receptor systems. In fact, for a few receptors, such as the somatostatin, ghrelin, and complement C5A receptors, basically all compounds found by screening using binding assays are agonists. In contrast, for the majority of receptors for which... 

Compound 686 (PNU-97018) is an orally active nonpeptide angiotensin II receptor antagonist without any agonistic activity that has an insurmountably high antihypertensive effect <2002CPB1022, 1995JEP1042, 1995MI880>. 

Sawada Y, Kayakiri H, Abe Y, et al. A new class of nonpeptide bradykinin B2 receptor ligands, incorporating a 4-aminoquinoline framework. Identification of a key pharmacophore to determine species difference and agonist/antagonist profile. 7 Med Chem 2004 47 2667-77. 

Small-molecule, nonpeptide thrombopoietin receptor agonists for oral use are being developed as a treatment for thrombocytopenia of various etiologies. 

Xaliproden is a selective nonpeptidic neurotropic-like compound that increases neuronal survival. This 5-HTagonist is also an NGF agonist and reduces apoptosis and improves neurogenesis. Phase 111 chnical trials are being conducted in patients... 

Opium alkaloids are nonpeptide agonists for the opioid peptide hormone receptors. The dried latex of Papaver somniferum (opium), or the seed capsule of the plant itself, are the sources of almost 25 alkaloids. Some simple isoquinolines from opium, like papaverine (5.86), are antispasmodics. The principal alkaloid ( 10% of the total) is morphine (3.11), which is also an isoquinoline (rings C and E) but can addihonally be considered a phenanthrene derivahve (rings A, B, and C). 

The drug candidate OPC-51803 is the first nonpeptide vasopressin V2-receptor-selective agonist that is in phase II clinical trials and the best chiral reduction to the intermediate acid (E) was with ruthenium acetate-[(5)-H8-BlNAP] that gave a 77 % ee (Figure 1.10). An improved catalyst system will be needed for large scale production. 

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