Pharmacologically active amine boranes

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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2604655R, 560155, 562565, 564 8, 4242484, 42424853, 42424854, 424263, 424304, 424311, 424319, 424320, 424325, A61K 3169, C07F 502

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043129897

ABSTRACT:
The use of amine boranes to inhibit the inflammation process is disclosed. These boranes, which are boron analogs of .alpha.-amino acids, effectively block the following: general inflammation, induced arthritis, and the writhing reflex associated with inflammation pain. The inflammation associated with pleurisy is also inhibited. The boron analogs are shown in vitro to inhibit the release of lysosomal enzymes from liver and polymorphonuclear neutrophils (PMNs). Further, prostaglandin synthesis is blocked by these compounds at a low concentration, viz, 10.sup.-6 M.
Liver oxidative phosphorylation processes are also uncoupled by these compounds, but PMN migration is unaltered at 10.sup.-4 M. The elevation of cyclic adenosine monophosphate in PMNs correlates positively with in vivo antiarthritic activity. Studies in rodents demonstrate that these boron analogs may be used at safe therapeutic doses. Several compounds per se are included within the scope of the invention.

REFERENCES:
Spielvogel, J. Am. Chem. Soc., 98, pp. 5702-5703, (1976).
Surjit, J. Chem. Soc., D., p. 1619, (1970).
Wisian-Neilson, Inorg. Chem., 17, pp. 2327-2329, 1978).
Weidig, Inorg. Chem., 13, pp. 1763-1768, (1974).
Wilson, "Textbook of Organic Medical and Pharmaceutical Chemistry", pp. 30, (1954).

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