Joung L. Goulet

Benzamide derivatives as blockers of Kv1.3 ion channel

The voltage-gated potassium channel, Kv1.3, is present in human T-lymphocytes. Blockade of Kv1.3 results in T-cell depolarization, inhibition of T-cell activation, and attenuation of immune responses in vivo. A class of benzamide Kv1.3 channel inhibitors has been identified. The structure-activity relationship within this class of compounds in two functional assays, Rb_Kv and T-cell proliferation, is presented. In in vitro assays, trans isomers display moderate selectivity for binding to Kv1.3 over other Kv1.x channels present in human brain.

Inhibition of stromelysin-1 (MMP-3) by peptidyl phosphinic acids

Abstract A series of phosphinic acid-containing peptide inhibitors of human stromelysin-1 (MMP-3) were prepared. The P1 through P3 subsites were varied in a systematic manner on analogs possessing an invariant P1′-P3′ segment. The in vitro activity of these compounds as inhibitors of stromelysin and collagenase is discussed.

Disubstituted pyrimidines as Lck inhibitors

We have developed a family of 4-benzimidazolyl-N-piperazinethyl-pyrimidin-2-amines that are subnanomolar inhibitors of Lck. A subset of these Lck inhibitors, with heterocyclic substituents at the benzimidazole C5, are also low-nanomolar inhibitors of cellular IL2 release.

The inhibition of C5a receptor binding by analogs of L-156,602, a cyclic hexadepsipeptide antibiotic

Abstract The cyclic hexadepsipeptide antibiotic L-156,602 ( 1 ) was found to be an inhibitor of anaphylatoxin C5a binding to its receptor (IC 50 =1.7 μg/mL). This compound also caused nonspecific degranulation of neutrophils, but not through interactions with the C5a or other receptors. The effects of chemical modification of the structure of 1 on C5a receptor inhibition and nonspecific actions are reported.