- The discovery of fused pyrrole carboxylic acids as novel, potent d-amino acid oxidase (DAO) inhibitors
-
The 'NMDA hypofunction hypothesis of schizophrenia' can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey the SARs of 1.
- Sparey, Tim,Abeywickrema, Pravien,Almond, Sarah,Brandon, Nick,Byrne, Noel,Campbell, Alister,Hutson, Pete H.,Jacobson, Marlene,Jones, Brian,Munshi, Sanjeev,Pascarella, Danette,Pike, Andrew,Prasad, G. Sridhar,Sachs, Nancy,Sakatis, Melanie,Sardana, Vinod,Venkatraman, Shankar,Young, Mary Beth
-
scheme or table
p. 3386 - 3391
(2009/04/06)
-
- FLUORO-SUBSTITUTED INHIBITORS OF D-AMINO ACID OXIDASE
-
This invention provides novel inhibitors of the enzyme D-amino acid oxidase as well as pharmaceutical compositions including the compounds of the invention. The invention also provides methods for the treatment and prevention of neurological disorders, such as neuropsychiatric and neurodegenerative diseases, as well as pain, ataxia and convulsion. The compounds of the invention have the general structure: wherein A is NH or S. Q is a member selected from CR1 and N. X and Y are members independently selected from O, S, CR2, N and NH. R1, R2 and R4 are members independently selected from H and F, provided that at least one member selected from R1, R2 and R4 is F. R6 is a member selected from O?X+ and OH, wherein X+ is a positive ion, which is a member selected from inorganic positive ions and organic positive ions.
- -
-
Page/Page column 70
(2008/06/13)
-
- Use of glycogen phosphorylase inhibitors
-
The invention provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof an effective amount of a glycogen phosphorylase inhibitor; effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent. The invention further provides methods of treating prophylactically an individual in whom Type 2 diabetes mellitus has not yet presented, but in whom there is an increased risk of developing such condition, which methods comprise administering to an individual in need thereof a pharmaceutical composition comprising effective amounts of a glycogen phosphorylase inhibitor and a non-glycogen phosphorylase inhibiting anti-diabetic agent; or effective amounts of a glycogen phosphorylase inhibitor and an anti-obesity agent.
- -
-
-
- Bicyclic pyrrolyl amides as glycogen phosphorylase inhibitors
-
This invention relates to compounds of Formula I or stereoisomers, pharmaceutically acceptable salts or prodrugs thereof or a pharmaceutically acceptable salts of the prodrugs. This invention also relates to pharmaceutical compositions comprising a compou
- -
-
-