869335-19-3

Usage

Core structure

pyrrolopyridine

Substitution

4-chloro

Alkyl group

1-[[2-(trimethylsilyl)ethoxy]methyl]

Usage

synthesis of pharmaceutical agents and organic compounds

Reactivity

useful for cross-coupling reactions

Building block

for the development of potential drug candidates

Heterocyclic structure

provides opportunities for bioactivity and further functionalization

Value

valuable chemical building block in medicinal and organic chemistry

Upstream product

• 76513-69-4 (2-trimethylethylsilylethoxy)methyl chloride 
• 55052-28-3 4-chloro-7-azaindole 
• 55052-24-9 1H-Pyrrolo[2,3-b]pyridine-7-oxide 
• 271-63-6 7-Azaindole 
• 1221714-47-1 4-chloro-2-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine 

Downstream Products

• 869335-24-0 N-(2-fluoro-4-nitrophenyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridin-4-amine 

Relevant academic research and scientific papers

PYRROLOPYRIDINE DERIVATIVE AND USE THEREOF IN PREVENTION AND TREATMENT OF PROTEIN KINASE-RELATED DISEASE

The present invention relates to a pyrrolopyridine derivative and a pharmaceutical composition comprising the same as an active ingredient for prevention or treatment of a protein kinase-related disease. The pyrrolopyridine derivative has excellent inhibitory activity against various protein kinases including LRRK2, DYRK1, and CLK1 and exhibits an excellent suppressive effect on the growth of triple-negative breast cancer cells. A pharmaceutical composition comprising the same as an active ingredient can be advantageously used for treating or preventing protein kinase-related diseases, inter alia, cancers, degenerative brain diseases, and inflammatory diseases, and specifically for treating triple-negative breast cancer.

SMALL MOLECULE INHIBITORS OF ULK1

The present technology is directed to compounds, compositions, and methods related to inhibition of ULK1 and treatment of cancers therefrom.

Trisubstituted Imidazoles with a Rigidized Hinge Binding Motif Act As Single Digit nM Inhibitors of Clinically Relevant EGFR L858R/T790M and L858R/T790M/C797S Mutants: An Example of Target Hopping

The high genomic instability of non-small cell lung cancer tumors leads to the rapid development of resistance against promising EGFR tyrosine kinase inhibitors (TKIs). A recently detected triple mutation compromises the activity of the gold standard third-generation EGFR inhibitors. We have prepared a set of trisubstituted imidazoles with a rigidized 7-azaindole hinge binding motif as a new structural class of EGFR inhibitors by a target hopping approach from p38α MAPK inhibitor templates. On the basis of an iterative approach of docking, compound preparation, biological testing, and SAR interpretation, robust and flexible synthetic routes were established. As a result, we report two reversible inhibitors 11d and 11e of the clinically challenging triple mutant L858R/T790M/C797S with IC50 values in the low nanomolar range. Furthermore, we developed a kinome selective irreversible inhibitor 45a with an IC50 value of 1 nM against the EGFR L858R/T790M double mutant. Target binding kinetics and metabolic stability data are included. These potent mutant EGFR inhibitors may serve as a basis for the development of structurally novel EGFR probes, tools, or candidates.

A pyrrolo-pyridine compound and its preparation method

The invention relates to a pyrrole-pyridine compound and a preparation method thereof. The compound is 1-((2-(trimethyl silicyl) ethyoxyl)methyl)-1H- pyrrole-[2,3-b] pyridine-2(3H)-ketone-4-carboxylic methyl ester. The preparation method of the compound comprises the following steps: (1) protecting the compound SM by use of 2-(trimethyl silicyl) ethyoxyl)methyl(sem) to obtain a compound 1; (2) carrying out dehydrogenation/oxidization on the compound 1 by virtue of pyridinium tribromide to obtain a compound 2; (3) carrying out bromine removal on the compound 2 by virtue of zinc and ammonium chloride at the normal temperature to obtain a compound 3; and (4) carrying out a carbonyl insertion reaction on the compound 3 by a high pressure kettle under the catalysis of Pd(dppf)Cl2 to produce a finial product compound 4. The final product has a wide application prospect in treating cancers.

INHIBITORS OF BRUTON'S TYROSINE KINASE

Disclosed herein are compounds that inhibit Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. In addition, reversible inhibitors of Btk are also described. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

Synthesis and evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as novel immunomodulators targeting Janus kinase 3

Janus kinases (JAKs) have been known to play crucial roles in modulating a number of inflammatory and immune mediators. Here, we describe a series of 1H-pyrrolo[2,3-b]pyridine derivatives as novel immunomodulators targeting JAK3 for use in treating immune diseases such as organ transplantation. In the chemical modification of compound 6, the introduction of a carbamoyl group to the C5-position and substitution of a cyclohexylamino group at the C4-position of the 1H-pyrrolo[2,3-b]pyridine ring led to a large increase in JAK3 inhibitory activity. Compound 14c was identified as a potent, moderately selective JAK3 inhibitor, and the immunomodulating effect of 14c on interleukin-2-stimulated T cell proliferation was shown. Docking calculations and WaterMap analysis of the 1H-pyrrolo[2,3-b]pyridine-5-carboxamide derivatives were conducted to confirm the substituent effects on JAK3 inhibitory activity.

Fragment-based discovery of new highly substituted 1H-pyrrolo[2,3-b]- and 3H-imidazolo[4,5-b]-pyridines as focal adhesion kinase inhibitors

Focal adhesion kinase (FAK) is considered as an attractive target for oncology, and small-molecule inhibitors are reported to be in clinical testing. In a surface plasmon resonance (SPR)-mediated fragment screening campaign, we discovered bicyclic scaffolds like 1H-pyrazolo[3,4-d]pyrimidines binding to the hinge region of FAK. By an accelerated knowledge-based fragment growing approach, essential pharmacophores were added. The establishment of highly substituted unprecedented 1H-pyrrolo[2,3-b]pyridine derivatizations provided compounds with submicromolar cellular FAK inhibition potential. The combination of substituents on the bicyclic templates and the nature of the core structure itself have a significant impact on the compounds FAK selectivity. Structural analysis revealed that the appropriately substituted pyrrolo[2,3-b]pyridine induced a rare helical DFG-loop conformation. The discovered synthetic route to introduce three different substituents independently paves the way for versatile applications of the 7-azaindole core.

HETEROCYCLIC COMPOUND AS PROTEIN KINASE INHIBITOR

Provided are novel heterocyclic compounds useful as anti-cancer drugs by suppressing protein kinase activities of growth factor receptors such as c-Met, pharmaceutical compositions containing the same, and methods for using the compound.