Molecular Pharmacology, Vol 15, 179-188, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

A Nuclear Magnetic Resonance Study of Compound 48/80

¹ Section on Molecular Pharmacology, Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20014
² Laboratory of Chemistry, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20014

Compound 48/80, a potent liberator of histamine from mast cells, is a polymer prepared by heating 4-methoxy-N-methylphenethylamine with an equimolar amount of formaldehyde in acid solution. We have attempted to elucidate the structure of 48/80 with the aid of carbon-13 nuclear magnetic resonance (NMR). The NMR spectrum of 48/80 suggests that it is a polymer in which methylene groups link 4-methoxy-N-methylphenethylamine moieties via their 3 and 3' positions. Some of the polymer chains of 48/80 are terminated by -CH₂OH groups. In accord with the findings of Read and co-workers (J. Med. Chem. 15: 320, 1972; ibid 16: 1292, 1973), the most active high molecular weight polymers appear to be hexamers; however, contrary to the suggestion of these authors, there was no evidence for the presence of tetrahydroisoquinoline moieties in 48/80. Light scattering and fluorescence probe measurements with 1-anilino-naphthalene-8-sulfonic acid indicate that at concentrations above 2 mg/ml (0.01 M based on the monomer molecular weight) compound 48/80 formed micelles. This is reflected in the NMR spectrum of 48/80 by the sharpness of the N-CH₃ resonance.

Note:
ACKNOWLEDGMENT The authors would like to thank Dr. Birandra Sinha for assistance with some of the synthetic organic chemical aspects of this paper.