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Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH).
TLDR
The discovery of 1 (tropifexor, LJN452), a novel and highly potent agonist of FXR is reported, which has advanced into phase 2 human clinical trials in patients with NASH and PBC. Expand
Arylaminoethyl carbamates as a novel series of potent and selective cathepsin S inhibitors.
TLDR
Lead optimization to a non-peptidic scaffold has resulted in a new class of potent, highly selective, and orally bioavailable cathepsin S inhibitors. Expand
HIGH CAPACITY SUBSTRATES AS A PLATFORM FOR A DNA PROBE ARRAY GENOTYPING ASSAY
TLDR
Porous surfaces derived from 70–100 nm size particles deposited in films from 0.15 to 2 microns thick exhibited excellent performance in light-directed oligonucleotide synthesis. Expand
Total synthesis of the lycopodium alkaloid (+)-serratezomine A.
TLDR
The first total synthesis of (+)-serratezomine A is described, which marks the first deployment of free-radical-mediated vinyl amination in a complex target synthesis and assembly of the contiguous array of six stereocenters is accomplished with high stereocontrol. Expand
Discovery and biological evaluation of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor.
TLDR
A novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported, which are full agonists with functional potency <50 nM and oral bioavailability in mice. Expand
The first azacyclopentenyl carbinyl radical isomerizations (ACCRI): independent use of steric and electronic (polarization) effects as gating elements.
The first examples of the azacyclopentenyl carbinyl radical isomerization are described within a series of enantiomerically enriched 2-substituted indolines, a substructure found extensively in bothExpand
Optimization of small molecule agonists of the thrombopoietin (Tpo) receptor derived from a benzo[a]carbazole hit scaffold.
TLDR
The lead optimization of a novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported and members of the scaffold have been identified which are full agonists that demonstrate cellular functional potency <50 nM. Expand
Discovery of structurally novel, potent and orally efficacious GPR119 agonists.
TLDR
Systematic optimization led to compound 36 with significantly improved in vitro activity and oral exposure, to elevate GLP1 acutely in an in vivo mouse model at a dose of 10mg/kg. Expand
Total synthesis of the Lycopodium alkaloid serratezomine A using free radical-mediated vinyl amination to prepare a β-stannyl enamine linchpin.
TLDR
Significant features of the synthesis include the first application of free radical mediated vinyl amination and Hwu's oxidative allylation in a total synthesis and an intramolecular lactonization via a transannular S(N)i reaction. Expand
Novel tricyclic pyrazolopyrimidines as potent and selective GPR119 agonists.
Systematic SAR optimization of the GPR119 agonist lead 1, derived from an internal HTS campaign, led to compound 29. Compound 29 displays significantly improved in vitro activity and oral exposure,Expand
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