Louisiana State University and Agricultural & Mechanical College

Other

Nicholas G Bazan

Carlos Sunkel

Julio Alvarez Builla Gomez

Victor L Marcheselli

Julio Alvarez Builla-G

Jay D Hunt

Haydee E Bazan

A new method to synthesize the platelet-activating factor antagonist which is a derivative of thienotriazolodiazepene, tetrahydro-4,7,8,10 methyl-1(chloro-2 phenyl)-6 (methosy-4 phenyl carbamoyl)-9 pyrido[4,3-:4,5] thieno[3,2-f] triazolo-1,2,4 [4,3-&#x3b1;] diazepine-1,4] (1) is disclosed. The compound synethesized by this new method has been designated 'LAU-8080' which has the same structure as the compound currently named in the literature as 'BN-50730.' LAU-8080 was shown to prevent photoreceptor cell death, inhibit pathological neovascularization in the retina, and minimize the loss of neurons due to ischemic-reperfusion damage due to stroke. Thus LAU-8080 can be used to treat the retinal diseases of age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy. It can also be used to minimize the neuronal damage due to stroke.

Synthesis and use of thienotriazolodiazepines

A novel use of platelet-activating factor antagonists that bind to intracellular PAF binding sites such as BN-50730 (tetrahedra-4,7,8,10 methyl-1 (chloro-1 phenyl)-6 (methoxy-4 phenyl-carbamoyl)-9 pyrido [4',3&#x2032;-4,5] thieno [3,2-f] triazolo-1,2,4 [4,3-a] diazepine-1,4) has been discovered. These intracellular-binding platelet-activating factor antagonists were found to inhibit both in vivo and in vitro tumor growth and angiogenesis where the angiogenesis is stimulated by basic fibroblast growth factor.

Platelet-activating factor antagonist inhibition of angiogenesis and tumor growth induced by basic fibroblast

5-lipoxygenase inhibitors: (2-azinylamino) quinone derivatives

A new series of derivatives of 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid and their synthesis have been discovered. Surprisingly, by modifying the substituent of the 3-carboxylic acid group, new compounds were produced with high activity as PAF receptor antagonists. These compounds were shown to protect neurons from brain damage that normally occurs in response to stroke and other cerebrovascular diseases. These compounds are also protective against edema generation resulting from traumatic breakdown of the blood-brain barrier. Moreover, these compounds were found to be non-toxic and cytoprotective of cells undergoing oxidative stress that would normally trigger apoptotic cell death; and to have activity as (a) antagonists of an intracellular platelet activating factor (&ldquo;PAF&rdquo;)-binding site, (b) inhibitors of PAF- and cytokine-mediated c-aminoterminal jun kinase (JNK) and extracellular regulated kinase (ERK), and (c) transcriptional inhibitors of COX-2 expression.

2,4,6-trimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid esters as neuroprotective drugs

Growing community of inventors

New Orleans, LA, United States of America

Nicholas G Bazan