US Government As Represented by the Secretary of the Army

Duke University

Other

USA As Represented by Secretary of the Navy

Andrew T McPhail

Iris H Hall

Bernard F Spielvogel

Chin-Chih Chiang

Eiichi Fujita

Masahito Ochiai

Han-Chin Ling

Ming L King

Novel boron dipeptide analogs and their corresponding amide derivatives which exhibit significant antihyperlipidemic and antineoplastic activities. Methods for preparing the boron containing compounds are disclosed as well as methods for utilizing the compounds to induce antihyperlipidemic and antineoplastic activity.

Boron dipeptide compounds

Amine-carboxyboranes (boron analogues of amino acids) which demonstrate sificant antitumor and antihyperlipidemic (cholesterol and /or triglyceride lowering) activities are disclosed.

Pharmacological active amine-carboxyboranes

Ester analogues of boron analogues of amino acid are disclosed. Also disced is a method of forming the ester analogues in high yield by condensation of the corresponding acids and alcohols with dicylohexylcarbodiimide at room temperature in dichloromethane. The disclosed compounds have shown interesting biological activities, in particular, hypolipidemic activity as well as significant antitumor and antiarthritic activities.

Esters of boron analogues of amino acids

This invention involves amine-carbamoylborane compounds of the formula

Amine-carbamoylborane adducts

Binuclear copper (II) carboxylates formed from amine-carboxyboranes

Substantially pure compounds having the general formula ##STR1## wherein (1) ##STR2## R.sup.2 is .beta.-hydroxy and R.sup.3 and R.sup.4 together form an oxygen bridge, or (2) ##STR3## R.sup.2 and R.sup.3 together form an additional carbon-carbon bond, and R.sup.4 is hydroxy, are disclosed. These compounds exhibit antileukemic activity against P388 lymphocytic leukemia in CDF.sub.1 mice and inhibitory activity in vitro against cells derived from human epidermoid carcinoma of the nasopharynx(KB) cells.

1H-Cyclopenta[b]benzofuran derivative and its analog

The use of a mine boranes to inhibit the inflammation process is disclosed. hese 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.

Pharmacologically active amine boranes

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.

Growing community of inventors

Durham, NC, United States of America

Andrew T McPhail