Specific irreversible antagonism of histamine receptors by photo

Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Parasitic organism or component thereof or substance...

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548342, A61K 31415

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active

043573410

ABSTRACT:
Specific method of irreversible antagonism of histamine receptors, especially H.sub.1 receptors, in, for example, isolated guinea pig vas deferens by 4(5)-[2-(4-azido-2-nitroanilino)ethyl]imidazole (AAH), which is a photoaffinity analog of histamine actuated unusually by light in the visible spectrum. Additionally, compounds of the present invention are represented by the formula ##STR1## wherein R.sub.1 and R.sub.2 represent an electron withdrawing group of the formula, H, --NO.sub.2, --Cl, --F, --Br, --I, --SO.sub.3 H. When two groups occur, it is not necessary that those groups be identical. In preferred compounds R.sub.1 is --NO.sub.2 and R.sub.2 is H and R.sub.1 is ortho to amine group.
R.sub.3, R.sub.4, R.sub.5 and R.sub.6 represent a proton or lower alkyl of straight and branched carbon chains. In preferred compounds R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are protons or methyl groups with not more than two of the four positions substituted with an alkyl group. Preference is given for R.sub.4 and R.sub.5.

REFERENCES:
Hogaboom et al., Science, 208:1273-1276, Jun. 13, 1980.
Fedan et al., European Journal of Pharmacology, 69:41-53, 1981.
Chowdhry et al., Ann. Rev. Biochem., 48:293-325, 1979.
Guillory et al., Meth. Enzymology, 46:259-288 (1977).
Bayley et al., Meth. Enzymology, 46:69-114 (1977).
Cooperman, Ageing, Carcinogenicity and Radiation Biology, Kendric (ed.), Plenum Press, NY, 1976, 315 ff.
Douglaf, "Histamine and 5-Hydroxytryptamine (Serotonin) and Their Antagonists", Goodman and Gilman's The Pharmacological Basis of Therapeutics, 6th ed., McMillan, 1980, pp. 609-619.

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