Antagonists neurokinin

Neurokinins comprise a group of peptides involved in nerve transmission. Specific members of this class of mediators control such diverse functions as visceral regulation and CNS function. The nonpeptide neurokinin antagonist talnetant (32-6), for example, has been evaluated for its effect on irritable bowel syndrome and urinary incontinence as well as depression and schizophrenia [36]. The quinoline portion of this compound is prepared by base-catalyzed Pfitzinger condensation of isatin (32-1) with the methoxy acetophenone (32-2). The methoxy ether in the product (32-3) is next cleaved by means of hydrogen bromide (32-4). Amide formation with the chiral a-phenylpropylamine (32-5) affords the neurokinin antagonist talnetant (32-6) [37]. 

Rupniak, N. M. J.and Hill, R. G. Neurokinin antagonists. In Novel aspects in pain management opioids and beyond, 1999, edited by J. Sawynok and A. Cowan, 135-155, Wiley-Liss, New York. 

The (7 )-4,4- and the 5,4-spirolactam systems were also used to induce a (1-turn in the H-Pro-Leu-Gly-NH2 sequence (i.e., 79 and 80, Scheme 30).111031 Analysis by X-ray crystallography indicated that the structures form a type-II 3-tumJ104l Previous studies 110 with a series of neurokinin antagonists had shown that the extended conformation is favored for the (/ )-4,4-spirolactam system however, the (5)-4,4-spirolactam demonstrated a type-II l-tum conformation. 

Five topics are reviewed in this volume. Chapter 1 traces the biochemical and medical significance of Vitamin D and its derivatives from the first quarter of this century, a field which continues to promise further valuable results. In contrast, the relatively recent development of neurokinin antagonists, especially NKl-selective compounds, is surveyed in Chapter 2. These compounds have potential for the treatment of pain, migraine, emesis and asthma. A plethora of types of compound structures have recently been found to possess selective antagonism for each of the neurokinin receptors. 

Neurokinins comprise a group of peptides involved in nerve transmission. Specific members of this class of mediators control such diverse functions as visceral regulation, and CNS function. The nonpeptide neurokinin antagonist talnetant (51), for example, is currently being evaluated for its effect on irritable bowel syndrome, urinary... 

Finally, much neurogenic inflammation within the airways is a consequence of release of the neuropeptides substance P and other neurokinins. Antagonists of these agents have proven to be particularly poor in the heatment of asthma but have been developed in therapy of chemotherapy-induced nausea and vomiting. Their efficacy in chronic cough remains to be determined. 

Cyclic peptide antibiotic. Prod, by Aspergillus flavipes. Neurokinin antagonist. Powder. Mp 160-164°. [ajj,... 

Appell, K. C., Chung, T. D. Y., Solly, K. J., and Chelsky, D. (1998) Biological characterization of neurokinin antagonists discovered through screening of a combinatorial library. J. Biomol. Screening 3, 19-27. 

SCHEME 48.3. Structure of the neurokinin antagonist ZD2249 5 and details of the Ti(IV) asymmetric sulfoxidation step. 

SA Bowden, J Nigel Burke, F Gray, S McKown, J Moseley, WO Moss, PM Murray, Ml Welham, MJ Young. A new approach to rapid parallel development of four neurokinin antagonists. Part 4. Synthesis of ZD2249 methoxy sulfoxide. Org. Process Res. Dev. 2004 8 33-44. 

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