Learn More
PF-956980 is a selective inhibitor of JAK3, related in structure to CP-690550, a compound being evaluated in clinical trials for rheumatoid arthritis and prevention of allograft rejection. PF-956980 has been evaluated against a panel of 30 kinases, and found to have nanomolar potency against only JAK3. Cellular and whole blood activity of this compound(More)
There is a critical need for safer and more convenient treatments for organ transplant rejection and autoimmune disorders such as rheumatoid arthritis. Janus tyrosine kinases (JAK1, JAK3) are expressed in lymphoid cells and are involved in the signaling of multiple cytokines important for various T cell functions. Blockade of the JAK1/JAK3-STAT pathway with(More)
We describe an approach to modulating the on-demand motion of catalytic polymer-based microengines via near-infrared (NIR) laser irradiation. The polymer multilayer motor was fabricated by the template-assisted layer-by-layer assembly and subsequently deposition of platinum nanoparticles inside and a thin gold shell outside. Then a mixed monolayer of a(More)
We describe a biodegradable, self-propelled bovine serum albumin/poly-l-lysine (PLL/BSA) multilayer rocket as a smart vehicle for efficient anticancer drug encapsulation/delivery to cancer cells and near-infrared light controlled release. The rockets were constructed by a template-assisted layer-by-layer assembly of the PLL/BSA layers, followed by(More)
A three-component, titanium-mediated synthesis of α-branched N-acylamines from commercial or readily accessible amides, aldehydes, and organometallic reagents is reported. The transformation proceeds under mild reaction conditions and tolerates a variety of functional groups (including nitrile, carbamate, olefin, basic amine, furan, and other sensitive(More)
The discovery and selection of a highly potent and selective NaV1.7 inhibitor PF-06456384, designed specifically for intravenous infusion, is disclosed. Extensive in vitro pharmacology and ADME profiling followed by in vivo preclinical PK and efficacy model data are discussed. A proposed protein-ligand binding mode for this compound is also provided to(More)
Herein we describe the structure-aided design and synthesis of a series of pyridone-conjugated monobactam analogues with in vitro antibacterial activity against clinically relevant Gram-negative species including Pseudomonas aeruginosa , Klebsiella pneumoniae , and Escherichia coli . Rat pharmacokinetic studies with compound 17 demonstrate low clearance and(More)
The addition of the SuperQuat enolate to five- and six-membered heterocyclic tert-butyl sulfinimines led to a high syn-selectivity of up to 99:1 in good to excellent yields. The reaction is tentatively proposed to proceed through an open-chain transition state with the presence of an α-heteroatom on the sulfinimine leading to high diastereoselectivities.(More)
A novel series of monocarbam compounds exhibiting promising antibacterial activity against multidrug resistant Gram-negative microorganisms is reported, along with the synthesis of one such molecule MC-1 (1). Also reported are structure-activity relationships associated with the in vitro and in vivo efficacy of 1 and related analogues in addition to the(More)