Rational targeting of active-site tyrosine residues using sulfonyl fluoride probes

…, CA Menard, A Narayanan, MD Parikh… - ACS Chemical …, 2015 - ACS Publications
This work describes the first rational targeting of tyrosine residues in a protein binding site
by small-molecule covalent probes. Specific tyrosine residues in the active site of the mRNA-…

Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for …

…, S Kwon, J Langille, MD Parikh… - Journal of medicinal …, 2018 - ACS Publications
Janus kinases (JAKs) are intracellular tyrosine kinases that mediate the signaling of numerous
cytokines and growth factors involved in the regulation of immunity, inflammation, and …

PF-07059013: a noncovalent modulator of hemoglobin for treatment of sickle cell disease

…, JJ Novak, TN O'Connell, MD Parikh… - Journal of Medicinal …, 2020 - ACS Publications
Sickle cell disease (SCD) is a genetic disorder caused by a single point mutation (β6 Glu →
Val) on the β-chain of adult hemoglobin (HbA) that results in sickled hemoglobin (HbS). In …

Chemoselective preparation of clickable aryl sulfonyl fluoride monomers: A toolbox of highly functionalized intermediates for chemical biology probe synthesis

O Fadeyi, MD Parikh, MZ Chen, RE Kyne Jr… - …, 2016 - Wiley Online Library
Sulfonyl fluoride (SF)‐based activity probes have become important tools in chemical
biology. Herein, exploiting the relative chemical stability of SF to carry out a number of …

Benzothiophene inhibitors of MK2. Part 2: Improvements in kinase selectivity and cell potency

…, MW Mahoney, RJ Mourey, MD Parikh - Bioorganic & Medicinal …, 2009 - Elsevier
Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs
with potencies of less than 500nM in a cell based assay. The selectivity of the inhibitors …

Demonstration of a Multikilogram-Scale Birch Reduction and Evaluation of Alternative Synthetic Routes to a Ketalized Cyclohexene Derivative

…, X Li, Z Liu, JC McWilliams, MD Parikh… - … Process Research & …, 2023 - ACS Publications
We report the successful manufacture of several >50 kg batches of a key intermediate via a
Birch reduction that utilized liquified ammonia as well as lithium metal. With an eye toward …

Aminopyrazole carboxamide bruton's tyrosine kinase inhibitors. irreversible to reversible covalent reactive group tuning

…, TN O'Connell, JF Ohren, MD Parikh… - ACS Medicinal …, 2018 - ACS Publications
Potent covalent inhibitors of Bruton’s tyrosine kinase (BTK) based on an aminopyrazole
carboxamide scaffold have been identified. Compared to acrylamide-based covalent reactive …

Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode

…, BA Reitz, KJ Mathis, BS Pierce, MD Parikh… - Bioorganic & medicinal …, 2010 - Elsevier
The work described herein demonstrates the utility of structure-based drug design (SBDD) in
shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting …

Porphyrins with exocyclic rings. Part 19: Efficient syntheses of phenanthrolinoporphyrins

TD Lash, Y Lin, BH Novak, MD Parikh - Tetrahedron, 2005 - Elsevier
5-Nitro-1,10-phenanthrolines react with isocyanoacetate esters in the presence of DBU in
THF to give excellent yields of the corresponding phenanthrolinopyrroles. These were …

Selectively targeting an inactive conformation of interleukin-2-inducible T-cell kinase by allosteric inhibitors

…, TJ McLellan, R Unwalla, C Choi, MD Parikh… - Biochemical …, 2014 - portlandpress.com
ITK (interleukin-2-inducible T-cell kinase) is a critical component of signal transduction in T-cells
and has a well-validated role in their proliferation, cytokine release and chemotaxis. ITK …