Warner-lambert Company

Chiron Corporation

Migenix, Inc.

Mitokor, Inc.

Walter H Moos

Haile Tecle

Anthony J Thomas

Soumitra S Ghosh

Robert E Davis

Bharat Kalidas Trivedi

Yazhong Pei

Michael R Pavia

David A Downs

Scott W Miller

David W Moreland

David J Lauffer

James A Bristol

Christen M Anderson

Tomas R Szabo

Jeffrey A Kester

Dane A Goff

Ronald N Zuckermann

Harriet W Hamilton

Eric J Martin

William Christensen Clevenger

Sandra Eileen Wiley

Stephen C Bergmeier

David C Spellmeyer

Gregory Stauber

Bruce D Roth

Donald E Butler

John S Kiely

John C Hodges

Mel C Schroeder

Sheila H DeWitt

Charles J Stankovic

Reyna J Simon

Stephen B Kent

Thomas Gary Heffner

Donna Reynolds Cody

Leonard Theodore Meltzer

Linda L Coughenour

Ronald N Zuckerman

Janice M Kerr

Stephen Douglas Barrett

Alexander James Bridges

William Chester Patt

Juan C Jaen

Bradley W Caprathe

John H Dodd

Stephen J Johnson

Corinne E Augelli-Szafran

Kevin R Shoemaker

David M Lustgarten

Adam A Galan

Kathryn B Sanders

Deedee L Szotek

Hasile Tecle

Compositions and methods are provided for producing adenine nucleotide translocator (ANT) polypeptides and fusion proteins, including the production and use of recombinant expression constructs having a regulated promoter. ANT ligands and compositions and methods for identifying ANT ligands, agents that bind ANT and agents that interact with ANT are also disclosed.

Production of adenine nucleotide translocator (ANT), novel ANT ligands and screening assays therefor

Production of adenine nucleotide translocator (ANT), novel ANT ligands and screening assays therefor.

Compounds for altering mitochondrial function and cellular responses

The present invention relates generally to mitochondria protecting agents for treating diseases in which mitochondrial dysfunction leads to tissue degeneration and, more specifically, to compounds, compositions and methods related to the same. The methods of this invention involve administration of a pharmaceutically effective amount of a mitochondria protecting agent to a warm-blooded animal in need thereof, and composition of this invention contain a mitochondria protecting agent in combination with a pharmaceutically acceptable carrier or diluent. Mitochondrial associated diseases which may be treated by the present invention include (but are not limited to) Alzheimer's Disease, diabetes mellitus. Parkinson's Disease, neuronal and cardiac ischemia. Huntington's disease and stroke.

Mitochondria protecting agents for treating mitochondria associated diseases

The present invention relates generally to mitochondria protecting agents for treating diseases in which mitochondrial dysfunction leads to tissue degeneration and, more specifically, to compounds, compositions and methods related to the same. The methods of this invention involve administration of a pharmaceutically effective amount of a mitochondria protecting agent to a warm-blooded animal in need thereof, and composition of this invention contain a mitochondria protecting agent in combination with a pharmaceutically acceptable carrier or diluent. Mitochondrial associated diseases which may be treated by the present invention include (but are not limited to) Alzheimer's Disease, diabetes mellitus, Parkinson's Disease, neuronal and cardiac ischemia, Huntington's disease and stroke.

A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two 'sub-monomers' directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amine bound to the support with an acylating agent comprising a leaving group capable of nucleophilic displacement by --NH.sub.2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a resin-bound .alpha.-haloacetamide) with a sufficient amount of a second sub-monomer comprising an --NH.sub.2 group, such as a primary amine, alkoxyamine, semicarbazide, acyl hydrazide, carbazate or the like. Repetition of the two step cycle of acylation and displacement gives the desired oligomers. The efficient synthesis of a wide variety of oligomeric NSGs using automated synthesis technology of the present method makes these oligomers attractive candidates for the generation and rapid screening of diverse peptidomimetic libraries. The oligomers of the invention, such as N-substituted glycines (i.e. poly NSGs) disclosed here provide a new class of peptide-like compounds not found in nature, but which are synthetically accessible and have been shown to possess significant biological activity and proteolytic stability.

Synthesis of N-substituted oligomers

A solid-phase method for the synthesis of N-substituted oligomers, such as poly (N-substituted glycines) (referred to herein as poly NSGs) is used to obtain oligomers, such as poly NSGs of potential therapeutic interest which poly NSGs can have a wide variety of side-chain substituents. Each N-substituted glycine monomer is assembled from two 'sub-monomers' directly on the solid support. Each cycle of monomer addition consists of two steps: (1) acylation of a secondary amine bound to the support with an acylating agent comprising a leaving group capable of nucleophilic is displacement by --NH.sub.2, such as a haloacetic acid, and (2) introduction of the side-chain by nucleophilic displacement of the leaving group, such as halogen (as a resin-bound .alpha.-haloacetamide) with a sufficient amount of a second sub-monomer comprising an --NH.sub.2 group, such as a primary amine, alkoxyamine, semicarbazide, acyl hydrazide, carbazate or the like. Repetition of the two step cycle of acylation and displacement gives the desired oligomers. The efficient synthesis of a wide variety of oligomeric NSGs using automated synthesis technology of the present method makes these oligomers attractive candidates for the generation and rapid screening of diverse peptidomimetic libraries. The oligomers of the invention, such as N-substituted glycines (i.e. poly NSGs) disclosed here provide a new class of peptide-like compounds not found in nature, but which are synthetically accessible and have been shown to possess significant biological activity and proteolytic stability.

A method for the multiple, simultaneous synthesis of compounds comprising the steps of: 1) providing an apparatus comprising a plurality of reaction tubes having filter members on their lower ends, a reservoir member for receiving the filter member, a holder member having a plurality of apertures for supporting the reaction tubes, and a manifold member adjacent to the holder member and enclosing the upper ends of the reaction tubes; 2) charging the apparatus with reactants required for synthesis; 3) synthesizing the compounds in solution; or optionally 4) cleaving the compounds from a solid support within the apparatus.

Apparatus and method for multiple simultaneous synthesis

Compounds of Formula 1 bind opioid receptors: ##STR1## wherein X and Y are each independently ##STR2##

Opiate receptor ligands

Pharmaceutically useful nitrogen containing cyclic oxime and amine substituted compounds are disclosed which are azabicyclo[2.2.2]oximes, azabicyclo[2.2.2]-amines, azabicyclo[3.2.1]oximes and amine containing heterocyclic oximes wherein the heterocyclic ring contains from 3 to 7 carbon atoms.

Azabicyclo and azacyclo oxime and amine cholinergic agents and methods

Compounds of the formula: ##STR1## are useful for treating conditions modulated by .alpha..sub.1 -adrenergic receptors.

Peptoid .alpha.-1 adrenergic receptor ligands

Peptoid alpha-1 adrenergic receptor ligands

Pharmaceutically useful nitrogen containing cyclic oxime and amine substituted compounds which are azabicyclo[2.2.1]oximes, azabicyclo[2.2.2]oximes, azabicyclo[2.2.1]amines, azabicyclo[2.2.2]amines, azabicyclo[3.2.1]oximes, and amine containing heterocyclic oximes wherein the heterocyclic ring contains from 3 to 7 carbon atoms are disclosed.

Growing community of inventors

Oakland, CA, United States of America

Walter H Moos