University System of Maryland

Pharmacia & Upjohn S.p.a.

Merrell Dow Pharmaceuticals

Astra Aktiebolag

The J. David Gladstone Institutes

The J. David Gladstone Institutes, a Testamentary Trust Established Under the Will of J. David Gladstone

Universita Delgi Studi Di Parma

Other

Cornell Research Foundation Inc.

Merrell Pharmaceuticals, Inc.

Aktiebolaget Astra

Pharmacia S.p.a.

Robert Schwarcz

Carmela Speciale

Francesco Gerald Salituro

Ian A McDonald

Michael G Palfreyman

Paul J Muchowski

Mats Torbjorn Linderberg

Paolo Guidetti

Joseph M Muchowski

Susanna Karin Bjork

Birgitta Kristina Gotthammar

Kerstin Margareta Persson

Johan Per Luthman

Mario Varasi

Alberto Bianchetti

Arturo Della Torre

Bruce M Baron

Luca Benatti

Barry K Carpenter

Gabriele Costantino

Jerome Breton

Etsuo Okuno

Monica Mosca

Laura Amori

James F Collins

Kenneth Curry

A derivative of nicotinic acid N-oxide is described having formula (I): that acts as inhibitor of enzyme 3-hydroxyanthranilate-3,4-dioxygenase (3HAO), and is thus able to reduce QUIN biosynthesis in vivo under excitotoxic or pathological conditions, said compound being at the same time also chemically stable towards auto-oxidation. 

Derivatives of nicotinic acid N-oxide, their preparation and their use as inhibitors of enzyme 3-hydroxyanthranilate-3, 4-dioxygenase

The present invention relates to compounds of formula Ia or Ib below and their tautomers and/or pharmaceutically acceptable salts and compositions and methods of uses thereof. 

Small molecule inhibitors of kynurenine-3-monooxygenase

The present invention relates to compounds of Formula I below and their tautomers or pharmaceutically acceptable salts, compositions and methods of uses thereof. 

The present invention relates to compounds of Formula I below and their tautomers or pharmaceutically acceptable salts, compositions and methods of uses thereof: 

Recombinant KAT enzyme and process for its preparation

Hydroxylated anthranilic acid derivatives

Disclosed are isolated DNAs encoding a kynurenine aminotransferase selected from the group consisting of: (a) an isolated DNA sequence which encodes rat KAT; (b) an isolated DNA sequence which hybridizes to the isolated DNA sequence of (a) above and which encodes a KAT enzyme; and (c) an isolated DNA sequence differing from the isolated DNA sequences of (a) and (b) above in codon sequence due to the degeneracy of the genetic code, and which encodes a KAT enzyme. Also disclosed are vectors and host cells containing the same; oligonucleotide probes for identifying kynurenine aminotransferase; and isolated and purified kynurenine aminotransferase.

Recombinant kat enzyme from rat

Substituted kynurenines and process for their preparation

The present invention relates to the use in the treatment of cognitive disorders associated with the aging processes of the brain and perinatal brain disorders of compounds which act as inhibitors of the enzyme kynurenine aminotransferase (KAT).

The present invention relates to novel derivatives of 3-hydroxyanthranilic acid, 3-HANA, of the general formula I ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and selected from H and alkyl; X is selected from alkylthio, arylthio, aryloxy, halogen and cyano; R.sup.3, R.sup.4 are the same or different and selected from halogen, methyl, fluoroalkyl, cyano and Z--R.sup.5 wherein Z is selected from CH.sub.n, NH.sub.m, O, S, SO.sub.2 and CO wherein n=1 or 2; m=0 or 1 and R.sup.5 is selected from alkyl, aryl and fluoroalkyl; or R.sup.3 and R.sup.4 together form a saturated or unsaturated ring system Y--V--Z wherein Y and Z, independently of each other, are as defined for Z above and V is selected from C.sub.1 -C.sub.3 alkylene or alkenylene, --N.dbd., --N.dbd.N-- and ##STR2## wherein R.sub.7 =H or alkyl; or a pharmaceutically acceptable salt thereof, methods and intermediates for their preparation, novel pharmaceutical compositions and the use thereof for inhibiting the enzyme 3-hydroxy-anthranilate oxygenase, 3-HAO, responsible for the production of the endogenous neurotoxin quinolinic acid, QUIN.

Compounds

3-hydroxy anthanilic acid derivatives

The present invention is directed to a class of 4,6-disubstituted tryptophan derivatives, 4,6-disubstituted kynurenines, their use as NMDA antagonists and to pharmaceutical compositions containing these compounds.

NMDA antagonism method

The present invention relates to novel derivatives of 3-hydroxyanthranilic acid, 3-HANA, of the general formula I ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and selected from H, alkyl, aryl and arylalkyl; X and Y are the same or different and selected from alkoxy, aryloxy, alkyl, alkylthio, arylthio, fluoroalkyl, halogen, cyano, OSO.sub.2 CH.sub.3, OSO.sub.2 CF.sub.3, OCF.sub.3 and SCF.sub.3 with the proviso that the compound of formula I wherein R.sup.1 and R.sup.2 =H, X=Br and Y=Me is excluded;

New compounds

Growing community of inventors

Baltimore, MD, United States of America

Robert Schwarcz