4487-57-4

Usage

Uses

Used in Pharmaceutical Industry:
2,4-DIBROMO-5-NITROPYRIDINE is used as a key intermediate compound for the synthesis of AKT kinase inhibitors. These inhibitors play a crucial role in the development of targeted therapies for various cancers by modulating the activity of AKT kinase, which is often overactive in cancer cells, contributing to tumor growth and survival.
2,4-DIBROMO-5-NITROPYRIDINE is also used as a building block in the development of antihypertensive agents. These agents help regulate blood pressure by targeting specific receptors or enzymes involved in the regulation of vascular tone and fluid balance in the body.

InChI:InChI=1/C5H2Br2N2O2/c6-3-1-5(7)8-2-4(3)9(10)11/h1-2H

Upstream product

• 607373-82-0 2-hydroxy-4-methoxy-5-nitro pyridine 
• 31872-62-5 4-methoxy-3-nitro-pyridine 
• 850663-54-6 4-chloro-2-hydroxy-5-nitropyridine 
• 13091-23-1 4-chloro-3-nitropyridine 

Downstream Products

• 913642-07-6 2-bromo-N-ethyl-5-nitro-4-pyridinamine 
• 935279-24-6 2-bromo-N⁴-ethyl-5-nitro-3,4-pyridinediamine 
• 850663-86-4 4-[6-bromo-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl]-1,2,5-oxadiazol-3-amine 
• 1021919-70-9 ((1R)-1-phenylethyl)(2-bromo-5-nitro(4-pyridyl))amine 
• 850663-78-4 2-bromo-5-nitro-N-phenyl-4-pyridinamine 
• 84487-15-0 2-bromo-5-nitropyridin-4-amine 
• 1234014-33-5 2-bromo-N-methyl-5-nitropyridin-4-amine 
• 50786-37-3 4,6-dibromopyridine-3-amine 
• 1449669-27-5 2-bromo-5-nitro-4-vinylpyridine 
• 1449669-28-6 2-(1-methyl-1H-pyrazol-4-yl)-5-nitro-4-vinylpyridine 
• 1449669-29-7 4-ethyl-6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-ylamine 
• 1449669-30-0 N-(4-ethyl-6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-1-methyl-1H-imidazo[4,5-c]pyridin-6-amine 
• 1449665-20-6 N-(4-ethyl-6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)-N,1-dimethyl-1H-imidazo[4,5-c]pyridin-6-amine 
• 1612171-82-0 (2-bromo-5-nitropyridin-4-yl)isopropylamine 

Relevant academic research and scientific papers

EGFR PROTEOLYSIS TARGETING CHIMERIC MOLECULES AND ASSOCIATED METHODS OF USE

The present disclosure relates to bifunctional compounds, which find utility as modulators of receptor tyrosine kinase (RTK) proteins. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand which binds to an E3 ubiquitin ligase and on the other end a moiety which binds a target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effectuate ubiquitination, and therefore, degradation (and inhibition) of the target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Noncovalent Mutant Selective Epidermal Growth Factor Receptor Inhibitors: A Lead Optimization Case Study

Because of their increased activity against activating mutants, first-generation epidermal growth factor receptor (EGFR) kinase inhibitors have had remarkable success in treating non-small-cell lung cancer (NSCLC) patients, but acquired resistance, through a secondary mutation of the gatekeeper residue, means that clinical responses only last for 8-14 months. Addressing this unmet medical need requires agents that can target both of the most common double mutants: T790M/L858R (TMLR) and T790M/del(746-750) (TMdel). Herein we describe how a noncovalent double mutant selective lead compound was optimized using a strategy focused on the structure-guided increase in potency without added lipophilicity or reduction of three-dimensional character. Following successive rounds of design and synthesis it was discovered that cis-fluoro substitution on 4-hydroxy- and 4-methoxypiperidinyl groups provided synergistic, substantial, and specific potency gain through direct interaction with the enzyme and/or effects on the proximal ligand oxygen atom. Further development of the fluorohydroxypiperidine series resulted in the identification of a pair of diastereomers that showed 50-fold enzyme and cell based selectivity for T790M mutants over wild-type EGFR (wtEGFR) in vitro and pathway knock-down in an in vivo xenograft model.

Structure-based drug design of novel, potent, and selective azabenzimidazoles (ABI) as ATR inhibitors

Compound 13 was discovered through morphing of the ATR biochemical HTS hit 1. The ABI series was potent and selective for ATR. Incorporation of a 6-azaindole afforded a marked increase in cellular potency but was associated with poor PK and hERG ion channel inhibition. DMPK experiments established that CYP P450 and AO metabolism in conjunction with Pgp and BCRP efflux were major causative mechanisms for the observed PK. The series also harbored the CYP3A4 TDI liability driven by the presence of both a morpholine and an indole moiety. Incorporation of an adjacent fluorine or nitrogen into the 6-azaindole addressed many of the various medicinal chemistry issues encountered. (Chemical Presented).

AMINOPYRIMIDINE COMPOUNDS AS INHIBITORS OF T790M CONTAINING EGFR MUTANTS

This invention relates to novel compounds of formula (I) which are inhibitors of T790M containing EGFR mutants, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of cancer. (Formula I)

IMIDAZO [4, 5 -C] PYRIDINE DERIVATIVES USEFUL FOR THE TREATMENT OF DEGENERATIVE AND INFLAMMATORY DISEASES

Wherein R1, L1, R3, R4, Cy, L2 and R5 are as defined herein. Novel imidazolopyridines according to Formula I, able to inhibit JAK are disclosed, these compounds may be prepared as a pharmaceutical composition, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, allergic or inflammatory conditions, autoimmune diseases, proliferative diseases, transplantation rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons.

Aminofurazans as potent inhibitors of AKT kinase

AKT inhibitors containing an imidazopyridine aminofurazan scaffold have been optimized. We have previously disclosed identification of the AKT inhibitor GSK690693, which has been evaluated in clinical trials in cancer patients. Herein we describe recent efforts focusing on investigating a distinct region of this scaffold that have afforded compounds (30 and 32) with comparable activity profiles to that of GSK690693.

ISOMERIC PURINONES AND 1H-IMIDAZOPYRIDINONES AS PKC-THETA INHIBITORS

A chemical genus of purinones and 1H-imidazopyridinones, which are useful as PKCθ inhibitors, and their methods of use are disclosed. The genus is represented by the Formula (I).

Discovery of aminofurazan-azabenzimidazoles as inhibitors of rho-kinase with high kinase selectivity and antihypertensive activity

The discovery, proposed binding mode, and optimization of a novel class of Rho-kinase inhibitors are presented. Appropriate substitution on the 6-position of the azabenzimidazole core provided subnanomolar enzyme potency in vitro while dramatically improving selectivity over a panel of other kinases. Pharmacokinetic data was obtained for the most potent and selective examples and one (6n) has been shown to lower blood pressure in a rat model of hypertension. Despite many available treatments, hypertension remains a prevalent problem. In fact, some 30% of hypertensive patients are unable to reach their blood pressure goals. Thus, a new anti-hypertensive treatment, which acts on a broader patient population, would be an important addition to existing treatments. A number of vasoconstrictive agents, including angiotensin II, endothelin-1, and urotensin-II, exert their effect through RhoA and the downstream kinase Rho-kinase (ROCK1).1 Because of its central role in the control of smooth muscle contraction, inhibition of ROCK1 could lead to a more broadly efficacious anti-hypertensive agent.2 ROCK1 inhibitors have been shown to relax vascular smooth muscle and lower blood pressure in several animal models of hypertension.3 Therefore, we began an effort to identify potent ROCK1 inhibitors with pharmacokinetic profiles consistent with once daily oral dosing.

INHIBITORS OF AKT ACTIVITY

Invented are novel 1 H-imidazo[4,5-c]pyridin-2-yl compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

PREPERATION OF 1,6-DISUBSTITUTED AZABENZIMIDAZOLES AS KINASE INHIBITORS

Novel inhibitors of Rho-kinases are disclosed.