Abstract: A method for analyzing the immunosuppressant activity of Kv1.3 inhibitors using the mini- and micro-pig. These pig models have been found to have K.sub.v 1.3 channels very similar to man both in function and setting of membrane potential of T-lymphocytes, and respond similarly in a mixed lymphocyte reaction (MLR) to the K.sub.v 1.3 channel blockers. The mini-pig and micro-pig provide useful in vivo animal models for studying the immunosuppressant activity of Kv1.3 channel blockers that would be expected to function in man.
Type:
Grant
Filed:
September 10, 1996
Date of Patent:
November 17, 1998
Assignee:
Merck & Co., Inc.
Inventors:
J. Thomas Blake, William P. Feeney, Gloria C. Koo, Althea D. Talento
Abstract: A method for the treatment of Meniere's disease comprising the administration of a medicament which modulates the IKs channel of the ear and thereby reducing endolymph production.
Type:
Grant
Filed:
June 24, 1997
Date of Patent:
October 6, 1998
Assignee:
Merck & Company, Inc.
Inventors:
Peter K. S. Siegl, Allan I. Goldberg, Michael R. Goldberg, Paul I. Chang
Abstract: The present invention relates to the process for the preparation of the substituted azetidinone having the formula: ##STR1## comprising a convergent synthesis wherein the azetidinone portion of the molecule is coupled to the lower benzodioxole portion via a base catalyzed addition to an isocyanate.
Type:
Grant
Filed:
October 23, 1996
Date of Patent:
September 15, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Joseph S. Amato, Raymond Cvetovich, Frederick W. Hartner
Abstract: A process for the preparation of Phosphodiesterase IV inhibitors is described. The process consists of eight chemical steps involving five isolations to prepare the title compound from readily available isovanillin in 35% overall yield (Scheme 1). The process is highlighted by: a) a highly diastereoselective Michael addition of phenyllithium using (1R, 2S) cis-aminoindanol as a chiral auxiliary, b) highly crystalline intermediates providing for efficient purifications, c) crystallization of the final compound as its CSA salt for excellent enantiomeric purity.
Type:
Grant
Filed:
April 22, 1997
Date of Patent:
September 15, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Woo-Baeg Choi, Hywyn R. D. Churchill, Joseph E. Lynch, Paul J. Reider, Ralph P. Volante
Abstract: A method of preventing, treating, terminating and protecting against cardiac arrhythmias, such as atrial, supraventricular and ventricular ectopy, tachycardia, flutter or fibrillation, including atrial, supraventricular and ventricular arrhythmias resulting from myocardial ischemic injury in a patient in need thereof, comprising administration of a selective I.sub.Ks antagonist and a beta-adrenergic receptor blocking agent, administered in combined therapy either simultaneously, separately or sequentially is presented. Additionally, a pharmaceutical preparation comprising a selective I.sub.Ks antagonist and a beta-adrenergic receptor blocking agent, wherein these compounds are administered simultaneously, separately or sequentially is presented.
Abstract: This invention relates to a heteromultimer and its use in screening pharmaceutically active compounds for modulators of maxi-K channel activity. Such modulators are useful in treating asthma, pregnant human myometrium, hypertension and angina, cerebral ischemia and in conditions where stimulation of neurotransmitter release is desired such as Alzheimer's disease and stimulation of damaged nerves.
Type:
Grant
Filed:
November 12, 1996
Date of Patent:
July 7, 1998
Assignee:
Merck & Co., Inc.
Inventors:
Gregory J. Kaczorowski, Maria L. Garcia, Reid J. Leonard, Owen B. McManus, Richard J. Swanson, Kimberly L. Folander