1622902-68-4

Usage

Biochem/physiol Actions

PF-04965842 is a Janus Kinase (JAK) inhibitor selective for JAK1 with an IC50 value of 29 nM for JAK1 compared to 803 nM for JAK2, >10000 nM for JAK3 and 1250 nM for Tyk2. JAKs mediate cytokine signaling, and are involved in cell proliferation and differentiation. PF-04965842 has been investigated as a possible treatment for psoriasis.

Upstream product

• 479633-63-1 4-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine 
• 10147-36-1 n-propanesulfonyl chloride 
• 90213-66-4 2,4-dichloro-7H-pyrrolo[2,3-d]pyrimidine 

Relevant academic research and scientific papers

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 the Treatment of Autoimmune Diseases

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 hematopoiesis. As JAK1 pairs with JAK2, JAK3, and TYK2, a JAK1-selective inhibitor would be expected to inhibit many cytokines involved in inflammation and immune function while avoiding inhibition of the JAK2 homodimer regulating erythropoietin and thrombopoietin signaling. Our efforts began with tofacitinib, an oral JAK inhibitor approved for the treatment of rheumatoid arthritis. Through modification of the 3-aminopiperidine linker in tofacitinib, we discovered highly selective JAK1 inhibitors with nanomolar potency in a human whole blood assay. Improvements in JAK1 potency and selectivity were achieved via structural modifications suggested by X-ray crystallographic analysis. After demonstrating efficacy in a rat adjuvant-induced arthritis (rAIA) model, PF-04965842 (25) was nominated as a clinical candidate for the treatment of JAK1-mediated autoimmune diseases.

Development of a Nitrene-Type Rearrangement for the Commercial Route of the JAK1 Inhibitor Abrocitinib

The development of a commercial route toward the JAK1 inhibitor abrocitinib is described. The application of a late-stage Lossen rearrangement provided the desired cis-diaminocyclobutane, which was subsequently sulfonylated using a novel water-tolerable triazole sulfonylating reagent to provide the active pharmaceutical ingredient.

METHOD FOR PRODUCING PYRROLO[2,3-D]PYRIMIDINE COMPOUND AND INTERMEDIATE AND METHOD FOR USING THE SAME

PROBLEM TO BE SOLVED: To provide a method for producing a pyrrolo[2,3-d]pyrimidine compound and an intermediate thereof and to provide a method for using the same. SOLUTION: There are provided a method for producing N-((1S,3S)-3-(methyl(7H-pyrrolo[2,3-d)p

TRICYCLIC JANUS KINASE 1 INHIBITORS, AND COMPOSITIONS AND METHODS THEREOF

Provided are novel class of therapeutics that are safe and effective inhibitors of Janus kinase 1 and pharmaceutical composition and methods of preparation and use thereof in the treatment of various diseases and disorders (e. g., inflammatory diseases, immune-mediated diseases or cancer).

PROCESS FOR PREPARATION OF ABROCITINIB

The present invention relates to crystalline abrocitinib characterized by X-ray powder diffraction (XRPD) spectrum having peak reflections at about 12.9, 14.7, 19.4, 23.2 and 25.2 ±0.2 degrees 2 theta, and process for its preparation. The present invention relates to amorphous solid dispersion comprising abrocitinib or salt thereof together with at least one pharmaceutically acceptable carrier and process for its preparation.

PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES USEFUL FOR INHIBITING JANUS KINASE

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, pharmaceutical compositions containing them, and therapeutic uses thereof.

PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES

Described herein are pyrrolo{2,3-d}pyrimidine derivatives, their use as Janus Kinase (JAK) inhibitors, and pharmaceutical compositions containing them.