The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras

Inhibitors of farnesyl protein transferase

The compounds of the formula ##STR1## wherein A, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as set forth above, are described. The compounds of formula I have an inhibitory activity on the natural enzyme renin and can accordingly be used in the form of pharmaceutical preparations for the control or prevention of high blood pressure and cardiac insufficiency.

amino acid derivatives

Nucleophilic and organometallic displacement reactions of allylic compounds: stereo-and regiochemistry

Compounds of formula (I) and their pharmaceutically acceptable salts inhibit matrix metalloproteases, such as stromelysin, gelatinase, matrilysin and collagenase, and are useful in the treatment of mammals having disease-states alleviated by the inhibition of such matrix metalloproteases.

Matrix metalloprotease inhibitors

Atrial arrhythmias, a major contributor to cardiovascular morbidity, are believed to be influenced by autonomic nervous system tone. The main purpose of this invention was to highlight new findings that have emerged in the study of effects of autonomic nervous system tone on atrial arrhythmias, and its interaction with class III antiarrhythmic drug effects. This invention evaluates the significance of sympathetic and parasympathetic activation by determining the effects of autonomic nervous system using a vagal and stellar ganglions stimulation, and by using autonomic nervous system neurotransmitters infusion (norepinephrine, acetylcholine). This invention evaluates the autonomic nervous system effects on the atrial effective refractory period duration and dispersion, atrial conduction velocity, atrial wavelength duration, excitable gap duration during a stable circuit (such atrial flutter circuit around an anatomical obstacle), and on the susceptibility of occurrence (initiation, maintenance and termination) of atrial re-entrant arrhythmias in canine. This invention also evaluates whether autonomic nervous system activation effects via a local neurotransimitters infusion into the right atria can alter those of class III antiarrhythmic drug, sotalol, during a sustained right atrial flutter. This invention represents an emergent need to set-up and develop a new class of anti-cholinergic drug therapy for the treatment of atrial arrhythmias and to combine this new anti-cholinergic class to antiarrhythmic drugs. Furthermore, this invention also highlights the importance of a local application of parasympathetic neurotransmitters/blockers and a catheter ablation of the area of right atrium with the highest density of parasympathetic fibers innervation. This may significantly reduce the occurrence of atrial arrhythmias and may preserve the antiarrhythmic effects of any drugs used for the treatment of atrial re-entrant arrhythmias.

Use of autonomic nervous system neurotransmitters inhibition and atrial parasympathetic fibers ablation for the treatment of atrial arrhythmias and to preserve drug effects

Non-peptidyl compounds characterized generally as β-aminoacyl aminodiol carbamates are useful as renin inhibitors for the treatment of hypertension.

Non-peptidyl beta-aminoacyl aminodiol carbamates as anti-hypertensive agents

Non-peptidyl compounds characterized generally as poly(aminoalkyl)aminocarbonyl aminodiol derivatives of amino acids are useful as renin inhibitors for the treatment of hypertension.

Aminoalkylaminocarbonyl aminodiol amino acid derivatives as anti-hypertensive agents

Synthesis and biological activities of substituted glycyrrhetic acids

The synthesis of 11β-alkyl-19-norsteroids: a novel class of potent steroid hormones—I : The synthesis of 11β-methyl and 11β-ethylestradiol

Stereoselective addition of lithioethyl acetate to Boc-l-prolinal. A convenient chiral synthetic building block for the pyrrolizidine alkaloid ring system

John S. Baran

Papers

Non-peptidyl beta-aminoacyl aminodiol carbamates as anti-hypertensive agents

Aminoalkylaminocarbonyl aminodiol amino acid derivatives as anti-hypertensive agents

Synthesis and biological activities of substituted glycyrrhetic acids

The synthesis of 11β-alkyl-19-norsteroids: a novel class of potent steroid hormones—I : The synthesis of 11β-methyl and 11β-ethylestradiol

Stereoselective addition of lithioethyl acetate to Boc-l-prolinal. A convenient chiral synthetic building block for the pyrrolizidine alkaloid ring system