33742-70-0

Usage

Uses

Used in Pharmaceutical Industry:
2-Methylamino-3-nitro-6-chloropyridine is used as a key intermediate in the synthesis of various medications. Its unique structure allows for the development of compounds with potential therapeutic activities, contributing to the advancement of new drug discoveries.
Used in Agrochemical Industry:
In the agrochemical sector, 2-Methylamino-3-nitro-6-chloropyridine serves as an essential intermediate in the production of pesticides. Its incorporation into these chemical formulations aids in the development of effective pest control solutions for agricultural applications.
Used in Research and Development:
2-Methylamino-3-nitro-6-chloropyridine is utilized in research and development for exploring its potential biological and therapeutic properties. Its unique chemical structure offers opportunities for investigating new applications and understanding its interactions with biological systems.
It is crucial to handle 2-Methylamino-3-nitro-6-chloropyridine with caution due to its toxic nature, ensuring proper safety measures are in place to prevent harm during its use in various applications.

InChI:InChI=1/C6H6ClN3O2/c1-8-6-4(10(11)12)2-3-5(7)9-6/h2-3H,1H3,(H,8,9)

Upstream product

• 16013-85-7 2,6-dicholoro-3-nitropyridine 
• 74-89-5 methylamine 
• 5470-18-8 2-Chloro-3-nitropyridine 

Downstream Products

• 89660-14-0 6-chloro-N²-methylpyridine-2,3-diamine 
• 882856-88-4 tert-butyl [(3R,4R)-1-[(6-methylamino)-5-nitropyridin-2-yl]-4-(2,4,5-trifluorophenyl)piperidin-3-yl]carbamate 
• 223133-11-7 6-(4-methoxymethoxy-2,3,5-trimethylphenoxy)-2-methylamino-3-nitropyridine 
• 172648-61-2 2-methylamino-3-nitro-6-phenylsulfanylpyridine 
• 94166-58-2 6-methoxy-2-methylamino-3-nitropyridine 
• 172648-39-4 6-ethoxy-2-methylamino-3-nitropyridine 
• 172648-42-9 6-isopropoxy-2-methylamino-3-nitropyridine 
• 172648-48-5 2-methylamino-3-nitro-6-phenylpyridine 
• 89660-28-6 1-phenyl-3-methyl-5-chloroimidazo<4,5-b>pyridin-2-one 
• 89660-20-8 5-chloro-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one 
• 172648-38-3 5-[4-(5-benzyloxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-ylmethoxy)benzyl]-3-triphenylmethylthiazolidine-2,4-dione 
• 172648-63-4 5-[4-(3-methyl-5-phenylsulfanyl-3H-imidazo[4,5-b]pyridin-2-ylmethoxy)benzyl]-3-triphenylmethylthiazolidine-2,4-dione 
• 172648-51-0 5-[4-(3-methyl-5-phenyl-3H-imidazo[4,5-b]pyridin-2-ylmethoxy)benzyl]-3-triphenylmethylthiazolidine-2,4-dione 
• 172648-41-8 5-[4-(5-ethoxy-3-methyl-3H-imidazo[4,5-b]pyridin-2-ylmethoxy)benzyl]-3-triphenylmethylthiazolidine-2,4-dione 

Relevant academic research and scientific papers

Optimization of Novel Aza-benzimidazolone mGluR2 PAMs with Respect to LLE and PK Properties and Mitigation of CYP TDI

Investigation of a novel amino-aza-benzimidazolone structural class of positive allosteric modulators (PAMs) of metabotropic glutamate receptor 2 (mGluR2) identified [2.2.2]-bicyclic amine 12 as an intriguing lead structure due to its promising physicochemical properties and lipophilic ligand efficiency (LLE). Further optimization led to chiral amide 18, which exhibited strong in vitro activity and attractive pharmacokinetic (PK) properties. Hypothesis-driven target design identified compound 21 as a potent, highly selective, orally bioavailable mGluR2 PAM, which addressed a CYP time-dependent inhibition (TDI) liability of 18, while maintaining excellent drug-like properties with robust in vivo activity in a clinically validated model of antipsychotic potential.

6-HETEROARYLOXY BENZIMIDAZOLES AND AZABENZIMIDAZOLES AS JAK2 INHIBITORS

The present disclosure provides 6-heteroaryloxy benzimidazole and azabenzimidazole compounds and compositions thereof useful for inhibiting JAK2.

BENZIMIDAZOLE DERIVATIVES AND AZA-BENZIMIDAZOLE DERIVATIVES AS JANUS KINASE 2 INHIBITORS AND USES THEREOF

The present disclosure provides compounds of Formula (I), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be kinase (e.g., Janus kinase (JAK), e.g., Janus kinase 2 (JAK2)) inhibitors. Also provided are pharmaceutical compositions and kits including the provided compounds. Further provided are methods of using the provided compounds, pharmaceutical compositions, and kits (e.g., for treating a disease (e.g., proliferative disease) in a subject in need thereof).

COMBINATIONS COMPRISING BENZODIOXOL AS GLP-1R AGONISTS FOR USE IN THE TREATMENT OF NASH/NAFLD AND RELATED DISEASES

In part, the invention provides a new combination comprising (1) a GLP-1R agonist and (2) an ACC inhibitor or a DGAT2 inhibitor, or a KHK inhibitor or FXR agonist. The invention further provides new methods for treating diseases and disorders, for example, fatty liver, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, nonalcoholic steatohepatitis with liver fibrosis, nonalcoholic steatohepotitis with cirrhosis, and nonalcoholic steatohepatitis with cirrhosis and with hepatocellular carcinoma or with a metabolic-related disease, obesity, and type 2 diabetes, for example, using the new combination described herein.

GLP-1 Receptor Agonists and Uses Thereof

Provided herein are 6-carboxylic acids of benzimidazoles and 4-aza-, 5-aza-, and 7-aza-benzimidazoles as GLP-1R agonists, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.

GLP-1 RECEPTOR AGONISTS AND USES THEREOF

Provided herein are 6-carboxylic acids of benzimidazoles and 4-aza-, 5-aza-, and 7-aza- benzimidazoles as GLP-1R agonists, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.

Sulfide Analogues of Flupirtine and Retigabine with Nanomolar KV7.2/KV7.3 Channel Opening Activity

The potassium channel openers flupirtine and retigabine have proven to be valuable analgesics or antiepileptics. Their recent withdrawal due to occasional hepatotoxicity and tissue discoloration, respectively, leaves a therapeutic niche unfilled. Metabolic oxidation of both drugs gives rise to the formation of electrophilic quinones. These elusive, highly reactive metabolites may induce liver injury in the case of flupirtine and blue tissue discoloration after prolonged intake of retigabine. We examined which structural features can be altered to avoid the detrimental oxidation of the aromatic ring and shift oxidation toward the formation of more benign metabolites. Structure–activity relationship studies were performed to evaluate the KV7.2/3 channel opening activity of 45 derivatives. Sulfide analogues were identified that are devoid of the risk of quinone formation, but possess potent KV7.2/3 opening activity. For example, flupirtine analogue 3-(3,5-difluorophenyl)-N-(6-(isobutylthio)-2-(pyrrolidin-1-yl)pyridin-3-yl)propanamide (48) has 100-fold enhanced activity (EC50=1.4 nm), a vastly improved toxicity/activity ratio, and the same efficacy as retigabine in vitro.

Flupirtine and retigabine as templates for ligand-based drug design of KV7.2/3 activators

Drug induced liver injury (DILI) and tissue discoloration led to the recent discontinuation of the therapeutic use of the closely related drugs flupirtine and retigabine, respectively. Experience gained with these drugs strongly suggests that heterotetramer, voltage-gated potassium channels 2 and 3 (KV7.2/3) are valid targets for effective treatment of pain and epilepsy. Because the adverse effects are not related to the mechanism of action, it appears promising to investigate chemical modifications of these clinically validated, drug-like leads. In the present retro-metabolic drug design study, a series of 43 compounds were synthesized and characterized with regard to KV7.2/3 opening activity and efficacy. The most active compound 22d displays excellent potency (EC50 = 4 nM) and efficacy (154%) as a KV7.2/3 opener. Limited aqueous solubility hampered toxicity testing at concentrations higher than 63 μM, but this concentration was nontoxic to two hepatocellular cell lines (HEP-G2 and TAMH) in culture. The slightly less active but more soluble compound 25b (EC50 = 11 nM, efficacy 111%) showed an improved toxicity/activity ratio compared to flupirtine by three orders of magnitude and represents an attractive lead structure for the development of safer analgesics and antiepileptics.

Flupirtine Analogues: Explorative Synthesis and Influence of Chemical Structure on KV7.2/KV7.3 Channel Opening Activity

Neuronal voltage-gated potassium channels KV7.2/KV7.3 are sensitive to small-molecule drugs such as flupirtine, even though physiological response occurs in the absence of ligands. Clinically, prolonged use of flupirtine as a pain medication is associated with rare cases of drug-induced liver injury. Thus, safety concerns prevent a broader use of this non-opioid and non-steroidal analgesic in therapeutic areas with unmet medical needs such as hyperactive bladder or neonatal seizures. With the goal of studying influences of chemical structure on activity and toxicity of flupirtine, we explored modifications of the benzylamino bridge and the substitution pattern in both rings of flupirtine. Among twelve derivatives, four novel thioether derivatives showed the desired activity in cellular assays and may serve as leads for safer KV channel openers.

GLP-1 Agonists and Uses Thereof

Provided herein are 6-carboxylic acids of benzimidazoles and 4-aza-, 5-aza-, 7-aza- and 4,7-diaza-benzimidazoles as GLP-1R agonists, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.