Privileged substructures are of potentially great importance in medicinal chemistry. These scaffolds are characterized by their ability to promiscuously bind to a multitude of receptors through a variety of favorable characteristics. This may include presentation of their substituents in a spatially defined manner and perhaps also the ability to directly bind to the receptor itself, as well as exhibiting promising characteristics to aid bioavailability of the overall molecule. It is believed that some privileged substructures achieve this through the mimicry of common protein surface elements that are responsible for binding, such as β- and gamma;-turns. As a result, these structures represent a promising means by which new lead compounds may be identified.

The combinatorial synthesis of bicyclic privileged structures or privileged substructures

Natural products: a continuing source of novel drug leads.

Natural products and their derivatives have historically been invaluable as a source of therapeutic agents. However, in the past decade, research into natural products in the pharmaceutical industry has declined, owing to issues such as the lack of compatibility of traditional natural-product extract libraries with high-throughput screening. However, as discussed in this review, recent technological advances that help to address these issues, coupled with unrealized expectations from current lead-generation strategies, have led to a renewed interest in natural products in drug discovery.

The evolving role of natural products in drug discovery

Practical methodologies for the synthesis of indoles.

3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described. Developed by reasoned modification of the known anxiolytic benzodiazepines, these compounds provide highly potent, orally effective ligands selective for peripheral (CCK-A) receptors, with binding affinities approaching or equaling that of the natural ligand CCK-8. The distinction between CCK-A receptors on the one hand and CNS (CCK-B), gastrin, and central benzodiazepine receptors on the other is demonstrated by using the structure-activity profiles of the new compounds. Details of the binding of these agents to CCK-A receptors are examined, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.

Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists

La presente invention concerne des composes representes par la formule (I) dans laquelle les variables sont definies ci-dessus, qui sont utiles pour traiter des maladies et des conditions mediees par le co-transporteur du D-glucose (SGLT), par exemple, le diabete. La presente invention concerne egalement des procedes de traitement de ces maladies et conditions, et des compositions etc. pour leur traitement.

Dérivé de glycoside et ses utilisations

L'invention concerne des composes de formule (IA) dans laquelle R1a, R1b( X, R2a, R2b, W, R3, R4, et R5 sont tels que definis dans le descriptif ainsi que des sels de ceux-ci pharmaceutiquement acceptables. Ces composes se sont averes agir comme inhibiteurs de MEK, ce qui peut etre utile dans le traitement de maladies hyperproliferatives, comme un cancer et une inflammation.

Derives sulfonamides heterocycliques utilises comme inhibiteurs de mek

La presente invention concerne des composes de formule (I), ou un de leurs sels pharmaceutiquement acceptables, ou R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A et n sont comme defini dans la presente. L'invention concerne egalement un derive deutere du compose de formule (I).

INHIBITEURS DE LA 17a-HYDROXYLASE/C17,20-LYASE

La presente invention concerne des composes representes par la formule (I) dans laquelle les variables sont definies comme presentement ci-dessus, qui sont utiles pour traiter des maladies et affections mediees par le co-transporteur de sodium D-glucose (SGLT), par exemple le diabete. L'invention concerne en outre des procedes de traitement de telles maladies et affections, et des compositions, etc., pour leur traitement.

Mark G. Bock

Papers

Dérivé de glycoside et ses utilisations

Derives sulfonamides heterocycliques utilises comme inhibiteurs de mek

INHIBITEURS DE LA 17a-HYDROXYLASE/C17,20-LYASE

Dérivés de glycoside et utilisations de ceux-ci