866546-10-3

Usage

Class

pyrrolopyridine derivatives

Structure

pyrrolo[2,3-b]pyridine ring system

Substitution

bromo-chloro at the 3 and 5 positions

Functional group

sulfonyl group attached to the 1 position

Use

building block in the synthesis of organic molecules and pharmaceuticals

Potential

biological activity and reactivity

Applications

medicinal chemistry and drug discovery.

InChI:InChI=1/C14H10BrClN2O2S/c1-9-2-4-11(5-3-9)21(19,20)18-8-13(15)12-6-10(16)7-17-14(12)18/h2-8H,1H3

Upstream product

• 866546-07-8 5-chloro-1H-pyrrolo[2,3-b]pyridine 
• 866318-90-3 2-amino-5-chloro-3-[(trimethylsilyl)ethynyl]pyridine 
• 211308-81-5 5-chloro-3-iodo-2-aminopyridine 
• 1072-98-6 5-chloro-2-pyridylamine 
• 866546-09-0 3-bromo-5-chloro-1 H-pyrrolo[2,3-b]pyridine 
• 98-59-9 p-toluenesulfonyl chloride 

Downstream Products

• 866546-11-4 5-chloro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine 
• 1346172-63-1 (2S,3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-1-(6-(5-chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrazin-2-yl)-N-(2,2,2-trifluoroethyl)azetidine-2-carboxamide 
• 1346172-68-6 tert-butyl (3R)-4-(6-{5-chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyrazin-2-yl)-3-[(2,2,2-trifluoroethyl)carbamoyl]piperazine-1-carboxylate 
• 1346172-70-0 (2R)-1-(6-{5-chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}pyrazin-2-yl)-N-(2,2,2-trifluoroethyl)piperazine-2-carboxamide hydrochloride 
• 1346172-78-8 2-(3-{5-chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridine-3-yl}-5H-pyrrolo[2,3-b]pyrazin-5-yl)-N-(2,2,2-trifluoroethyl)acetamide 
• 1346172-81-3 methyl 1-[(6-{5-chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-pyrazin-2-yl)oxy]cyclopropanecarboxylate 
• 1346172-89-1 methyl 6-{5-chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-pyrazine-2-carboxylate 
• 1346172-93-7 diethyl (6-{5-chloro-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-pyrazin-2-yl)propanedioate 
• 1363407-75-3 potassium (5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)trifluoroborate 
• 1346172-28-8 tert-butyl N-{6-[5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrazin-2-yl}-L-alaninate 
• 1346172-29-9 N-{6-[5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrazin-2-yl}-L-alanine 
• 1346172-30-2 N₂-{6-[5-chloro-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]pyrazin-2-yl}-N-(2,2,2-trifluoroethyl)-L-alaninamide 
• 1422051-72-6 (R)-3-(2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-pyrimidin-4-ylamino)-4,4-dimethylpentanoic acid 

Relevant academic research and scientific papers

PYRROLO[2,3-B]PYRIDIN DERIVATIVES AS INHIBITORS OF INFLUENZA VIRUS REPLICATION

Provided herein are compounds of Formula A, B or C that can inhibit the replication of influenza viruses, reduce the amount of influenza viruses, and/or treat influenza.

Synthesis of Differentially Protected Azatryptophan Analogs via Pd2(dba)3/XPhos Catalyzed Negishi Coupling of N-Ts Azaindole Halides with Zinc Derivative from Fmoc-Protected tert-Butyl (R)-2-Amino-3-iodopropanoate

Unnatural amino acids play an important role in peptide based drug discovery. Herein, we report a class of differentially protected azatryptophan derivatives synthesized from N-tosyl-3-haloazaindoles 1 and Fmoc-protected tert-butyl iodoalanine 2 via a Neg

PYRROLOPYRIMIDINE DERIVATIVES USEFUL AS INHIBITORS OF INFLUENZA VIRUS REPLICATION

Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient a safe and effective amount of a compound represented by any of Formulas l-lll, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a safe and effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

Discovery of Novel, Orally Bioavailable β-Amino Acid Azaindole Inhibitors of Influenza PB2

In our efforts to develop novel small-molecule inhibitors for the treatment of influenza, we utilized molecular modeling and the X-ray crystal structure of the PB2 subunit of the influenza polymerase to optimize a series of acyclic β-amino acid inhibitors, highlighted by compound 4. Compound 4 showed good oral exposure in both rat and mouse. More importantly, it showed strong potency versus multiple influenza-A strains, including pandemic 2009 H1N1 and avian H5N1 strains and showed a strong efficacy profile in a mouse influenza model even when treatment was initiated 48 h after infection. Compound 4 offers good oral bioavailability with great potential for the treatment of both pandemic and seasonal influenza.

Discovery of VX-509 (Decernotinib): A Potent and Selective Janus Kinase 3 Inhibitor for the Treatment of Autoimmune Diseases

While several therapeutic options exist, the need for more effective, safe, and convenient treatment for a variety of autoimmune diseases persists. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. We screened our compound library against JAK3, a key signaling kinase in immune cells, and identified multiple scaffolds showing good inhibitory activity for this kinase. A particular scaffold of interest, the 1H-pyrrolo[2,3-b]pyridine series (7-azaindoles), was selected for further optimization in part on the basis of binding affinity (Ki) as well as on the basis of cellular potency. Optimization of this chemical series led to the identification of VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft model (HvG). On the basis of these findings, it appears that VX-509 offers potential for the treatment of a variety of autoimmune diseases.

Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2

In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay (Wagaman, P. C., Leong, M. A., and Simmen, K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105-114) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.

AZAINDOLES AS JANUS KINASE INHIBITORS

The present invention provides compounds of formula I: or a pharmaceutically acceptable salt thereof. Compounds of formula I are inhibitors of Janus kinases and as such are useful for the treatment of various diseases and conditions mediated by said enzym