Because of a preconceived notion that eliminating reactive metabolite (RM) formation with
new drug candidates could mitigate the risk of idiosyncratic drug toxicity, the potential for RM …

N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (14, PHA-543,613), a
novel agonist of the α7 neuronal nicotinic acetylcholine receptor (α7 nAChR), has been …

In order that the necessity and the substance of the spirit may be more fully shown, we must
revisit and recall the doctrines of the ancient philosophers. The Academics4 were the first to …

Proline-rich tyrosine kinase 2 (PYK2) is a cytoplasmic, non-receptor tyrosine kinase implicated
in multiple signaling pathways. It is a negative regulator of osteogenesis and considered …

Novel mechanisms of action and new chemical scaffolds are needed to rejuvenate antibacterial
drug discovery, and riboswitch regulators of bacterial gene expression are a promising …

The synthesis, in vitro properties, and in vivo pharmacokinetics for a series of sulfoximine-substituted
trifluoromethylpyrimidines as inhibitors of proline-rich tyrosine kinase, a target for …

A novel set of azabicyclic aryl amides have been identified as potent and selective agonists
of the α7 nAChR. A two-pronged approach was taken to improve the potential hERG liability …

A novel α7 nAChR agonist, N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide
(3a, PHA-709829), has been identified for the potential treatment of cognitive …

A novel series of pyrazolopyrazines is herein disclosed as mGluR5 negative allosteric
modulators (NAMs). Starting from a high-throughput screen (HTS) hit (1), a systematic structure–…

Inhibition of mPGES-1, the terminal enzyme in the arachidonic acid/COX pathway to regulate
the production of pro-inflammatory prostaglandin PGE2, is considered an attractive new …