Abbott Laboratories Corporation

Abbvie Inc.

Philip J Hajduk

Stephen W Fesik

David John Augeri

Sheela A Thomas

Thorsten K Oost

Xilu Wang

Michael D Wendt

Wang Shen

Aaron R Kunzer

Milan Bruncko

Hong Ding

William J McClellan

Saul H Rosenberg

Daniel A Dickman

Andrew M Petros

Jurgen Dinges

Edward T Olejniczak

David G Nettesheim

Steven A Baumeister

Thomas Dale Penning

David A Betebenner

Steven K Davidsen

Vincent L Giranda

Yan Guo

Daryl Richard Sauer

Kathy A Sarris

Richard A Craig

Michael R Michaelides

David D Nettesheim

Jamie R Giesler-Stacey

Thorsten Oost

The present invention relates to 1H-benzimidazole-4-carboxamides of formula (I), their preparation, and their use as inhibitors of the enzyme poly(ADP-ribose)polymerase for the preparation of drugs.

Potent PARP inhibitors

N-Benzoyl arylsulfonamides having the formula are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.

N-acylsulfonamide apoptosis promoters

N-Benzoyl arylsulfonamides having the formula are BCL-X1 inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-X1 inhibiting compositions and methods of promoting apoptosis in a mammal.

Inhibitors of matrix metalloproteinases

The present invention provides a process for identifying compounds which bind to a specific target molecule. The process comprises the steps of: a) generating a first T.sub.2 - or diffusion-filtered proton spectrum of one or a mixture of chemical compounds; b) exposing one or a mixture of chemical compounds to the target molecule; c) generating a second T.sub.2 - or diffusion-filtered proton spectrum of one or a mixture of chemical compounds that has been exposed the target molecule in step (b); and d) comparing said first and second T.sub.2 - or diffusion-filtered proton spectra to determine differences between said first and said second spectra, the differences identifying the presence of one or more compounds that are ligands which have bound to the target molecule.

Use of one-dimensional nuclear magnetic resonance to identify ligands to

The present invention provides a process of designing compounds which bind to a specific target molecule. The process includes the steps of a) identifying a first ligand to the target molecule using two-dimensional .sup.15 N/.sup.1 H NMR correlation spectroscopy; b) identifying a second ligand to the target molecule using two-dimensional .sup.15 N/.sup.1 H NMR correlation spectroscopy; c) forming a ternary complex by binding the first and second ligands to the target molecule; d) determining the three dimensional structure of the ternary complex and thus the spatial orientation of the first and second ligands on the target molecule; and e) linking the first and second ligands to form the drug, wherein the spatial orientation of step (d) is maintained.

Use of nuclear magnetic resonance to design ligands to target

The present invention provides a process for identifying compounds which bind to a specific target molecule. The process includes the steps of a) generating a first two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of a .sup.15 N-labeled target molecule; b) exposing the labeled target molecule to one or a mixture of chemical compounds; c) generating a second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectrum of the labeled target molecule that has been exposed to one or a mixture of compounds in step (b); and d) comparing said first and second two-dimensional .sup.15 N/.sup.1 H NMR correlation spectra to determine differences between said first and said second spectra, the differences identifying the presence of one or more compounds that are ligands which have bound to the target molecule.

Use of nuclear magnetic resonance to identify ligands to target

Growing community of inventors

Mundelein, IL, United States of America

Philip J Hajduk