Synthesis and Hypolipidemic Activity of Amine‐Carboxyboranes, and Their Amides and Esters in Rodents

Abstract

A series of amine carboxyboranes including their amides and esters were synthesized and shown to have potent hypolipidemic activity in rodents at 20 mg/kg/day. Ethylamine carboxyborane, di-n-propylamine-carboxyborane, trimethylamine-carbomethoxyborane, n-butylamine carbomethoxyborane, methylamine-N-ethyl carbamoylborane and trimethylamine-N-n-octyl carbamoylborane were the most potent derivatives demonstrating hypocholesterolemic and hypotriglycemic activities in rats orally at 20 mg/kg/day. These derivatives lowered tissue lipids, e.g. cholesterol, in the rat liver, small intestine and aorta. The fecal lipids were elevated. Furthermore, the agents lowered cholesterol and triglycerides in the serum VLDL and LDL fractions but caused elevations in the HDL fraction after 14 days. The agents inhibited hepatic enzymatic activities of rate limiting steps involved in lipid metabolism, e.g. ATP dependent citrate lyase, sn-glycerol-3-phosphate acyltransferase and phosphatidylate phosphohydrolase.

Synthesis and Pharmacological Activities of Amine-Boranes

“…Another boronated trimethylamine derivative, its N-noctyl amide, trimethylamine-N-n-octyl carbamoylborane, also demonstrated potent hypolipidemic activity [51]. In mice at 20 mg/kg/day, I.P., it lowered serum cholesterol and triglyceride levels 49 and 55%, respectively.…”

Synthesis, cytotoxicity, hypolipidemic and anti‐inflammatory activities of amine—boranes and esters of boron analogues of choline and thiocholine

“…Their activity in the Llzlo screen was comparable with those of selected aminecarboxyboranes,z amine-cyanoboranes,4 heterocyclic amin+ boranes,S tricyclohexyl-and triphenylphosphin+boranes,6 and metal complexes and boron-substituted salts.9 All of the derivatives mentioned previously were more active in the LlzlO screen than the di-and tripeptide boron derivatives. 3 Human colon carcinoma growth was reduced by 5-13; Tmolt, leukemia growth by 1 and 5-13; HeLa-S3 uterine carcinoma growth by 1-13; KB naeopharynx growth by 1, 5-9, and 13; osteosarcoma growth by 1,3,5-9,12, and 13; and brain glioma growth by 1, 10, and 12. The activity of 5, 7,9, 10, and 11 against colon adenocarcinoma growth is of particular interest because few commerical agents possess activity againat human colon adenocarcinoma growth.…”

Synthesis and Structural Investigation of Internally Coordinated α-Amidoboronic Acids

“…Such intramolecular five-membered-ring motifs with a B−O dative bond have been observed in esters derived from boronic acids, − and postulated as intermediates in the stereoselective reduction of neighboring carbonyl groups. − However, relatively little is known about the factors associated with the formation of these intramolecular (:OC−N−C−B) rings, or their influence on the therapeutic efficacy of potential drugs. It should be mentioned that the presence of intramolecular B−N dative bonds has been correlated to some unexpected physiological behavior. − …”