Biological activity anti-histamine

Functionalized oxadiazoles have received considerable attention in the pharmaceutical industry as heterocyclic amide and ester isosteres [95]. Oxadiazoles have been employed in the design of biologically active templates, e. g. core structures for muscarinic agonists, kinase inhibitors, anti-inflammatory agents, histamine H3 antagonists, monoaminic oxidase inhibitors, etc. 

Chromone derivatives, in particular 2-spiro-chroman-4(lF/)-ones, are ubiquitous in nature and possess various biological activities which include antiarrhythmic, anti-HIV, antidiabetic, acetyl-CoA carboxylase (ACC) inhibitor, vanilloid receptor antagonist, growth hormone secretagogues, histamine receptor antagonist, and... 

Table IX contains the structures of some of the carbinols (94) that have been prepared by reaction of 2-thienylorganometallic compounds with esters in almost every case dehydration of the carbinol was also reported. Many of the compounds listed here and the alkenes derived from them are anti-histaminic, anticholinergic, or spasmolytic. However, not all the papers and patents referred to give details of biological evaluation, so no survey of biological activity is attempted.

IKCNCKRHVl KPHICRKICG KNa (disulfide bonds C -C /C -C ), a cationic 22-peptide amide. MCDP is a component of the bee venom which contains several biologically active non-peptide substances, as weU as two more major peptides, the hemolytic peptide melittin, the neurotoxic peptide apamin, together with a number of minor peptides. like apamin, MCDP blocks Ca -dependent K channels in neurons. MCDP causes mast cell degranulation and histamine release at low concentrations, and has anti-inflammatory activity at higher concentrations [E. M. Dotimas et al., Biochim. Biophys. Acta 1987, 911,285 W. E. Steinmetz et al.. Peptide Res. 1994, 7,77 A. Buku, Peptides 1999,20,415]. 

Interleukin-1 (IL-1) produced by monocytes and several other cell types [70, 146] has a wide array of biological properties, including T cell activation and inflammatory interactions with muscle, liver, fibroblasts, brain and bone [70, 146], IL-1, both natural and recombinant, has been shown to release histamine from human basophils and from human adenoidal mast cells [70,146,151] and this release was abolished by an IL-1 antibody. However, the average release produced by 10 units of IL-1 was less than 20% and there was considerable variability between populations of basophils in the extent of histamine release. Moreover, the secretory response elicited was quite slow (within 15 min) compared with that of other peptides [151]. Desensitization of the basophils by anti-IgE serum had no effect on the subsequent IL-1 response, suggesting different mechanisms of action [ 151], as has been the case with other peptides. Interestingly, the portion of the IL-1 molecule that is responsible for its immu-nostimulatory activity appears to be separate from that portion responsible for its proinflammatory effects [152]. However, that portion of the molecule responsible for eliciting basophil and mast-cell histamine release has not as yet been defined. 

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