2587-03-3

Usage

Uses

Used in Organic Synthesis:
2,6-Dichloro-4-nitraminopyridine is used as a synthetic intermediate for the development of a wide range of organic compounds. Its unique chemical structure, featuring two chlorine atoms at the 2nd and 6th positions and a nitro group attached to the 4th position of the pyridine ring, makes it a versatile starting material for the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 2,6-Dichloro-4-nitraminopyridine is utilized as a key component in the synthesis of various drug candidates. Its reactivity and structural diversity allow for the creation of novel therapeutic agents with potential applications in treating a variety of medical conditions.
Used in Agrochemical Industry:
2,6-Dichloro-4-nitraminopyridine also finds application in the agrochemical industry, where it is employed in the development of new pesticides and other crop protection agents. Its chemical properties enable the design of innovative molecules with enhanced efficacy and selectivity, contributing to more effective and environmentally friendly agricultural practices.
Used in Dye and Pigment Industry:
The compound is also used as an intermediate in the synthesis of dyes and pigments, where its unique color properties and chemical stability contribute to the development of new and improved colorants for various applications, including textiles, plastics, and printing inks.

InChI:InChI=1/C5H4Cl2N3O2/c6-4-1-3(9-10(11)12)2-5(7)8-4/h1-2H,(H,8,9)(H,11,12)/q+1

Upstream product

• 2587-02-2 2,6-dichloro-[4]pyridylamine 
• 10132-07-7 4-amino-2,6-dichloropyrimidine 
• 159178-03-7 2,6-dichloro-4-isocyanatopyridine 
• 81001-09-4 2,6-dichloropyridine-4-carbonylazide 
• 42521-08-4 2,6-dichloroisonicotinoyl chloride 
• 5398-44-7 2,6-dichloropyridine-4-carboxylic acid 
• 99-11-6 citrazinic acid 
• 42521-09-5 methyl 2,6-dichloroisonicotinate 
• 2587-00-0 2,6-dichloropyridine N-oxide 
• 2402-78-0 2,6-dichloropyridine 
• 25194-01-8 4-nitro-2,6-dichloro-pyridine 

Downstream Products

• 1313726-52-1 tert-butyl (2,6-dichloro-3-nitropyridin-4-yl)carbamate 
• 1443830-80-5 6-[(1,3-benzodioxol-5-ylmethyl)(cyclohexyl)amino]-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile 
• 944388-71-0 4-amino-6-chloro-3-nitropyridine-2-carbonitrile 
• 1400586-21-1 7-[3,4-bis(methyloxy)phenyl]-N-{[(3S)-3-fluoro-3-piperidinyl]methyl}pyrido[3,4-b]pyrazin-5-amine hydrochloride 
• 1457967-09-7 1-benzyl-2-butyl-6-phenethyl-1H-imidazo[4,5-c]pyridin-4-amine 
• 1457967-08-6 1-benzyl-2-butyl-6-(4-(trifluoromethoxy)benzyl)-1H-imidazo[4,5-c]pyridin-4-amine 
• 1457967-06-4 1-benzyl-2-butyl-6-(4-methylbenzyl)-1H-imidazo[4,5-c]pyridin-4-amine 
• 1457967-04-2 1,6-dibenzyl-2-butyl-1H-imidazo[4,5-c]pyridin-4-amine 
• 1457967-03-1 1-benzyl-2-butyl-6-(thiophen-3-yl)-1H-imidazo[4,5-c]pyridin-4-amine 
• 1457967-02-0 1-benzyl-2-butyl-6-(furan-3-yl)-1H-imidazo[4,5-c]pyridin-4-amine 
• 1457967-01-9 1-benzyl-2-butyl-6-(pyridin-3-yl)-1H-imidazo[4,5-c]pyridin-4-amine 
• 1457966-98-1 1-benzyl-2,6-dibutyl-1H-imidazo[4,5-c]pyridin-4-amine 
• 1457967-45-1 C₃₃H₄₄N₄ 
• 1457967-44-0 C₃₃H₄₁F₃N₄O 

Relevant academic research and scientific papers

Discovery of MK-4688: An Efficient Inhibitor of the HDM2-p53 Protein-Protein Interaction

Identification of low-dose, low-molecular-weight, drug-like inhibitors of protein-protein interactions (PPIs) is a challenging area of research. Despite the challenges, the therapeutic potential of PPI inhibition has driven significant efforts toward this goal. Adding to recent success in this area, we describe herein our efforts to optimize a novel purine carboxylic acid-derived inhibitor of the HDM2-p53 PPI into a series of low-projected dose inhibitors with overall favorable pharmacokinetic and physical properties. Ultimately, a strategy focused on leveraging known binding hot spots coupled with biostructural information to guide the design of conformationally constrained analogs and a focus on efficiency metrics led to the discovery of MK-4688 (compound 56), a highly potent, selective, and low-molecular-weight inhibitor suitable for clinical investigation.

AZABENZIMIDAZOLE DERIVATIVES AS PI3K BETA INHIBITORS

The present invention relates to azabenzimidazole derivatives of Formula (I) (I) wherein the variables have the meaning defined in the claims. The compounds according to the present invention are useful as pI3Kβ inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active 10 ingredient as well as the use of said compounds as a medicament.

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).

PYRIDO[3,4-B]PYRAZINE DERIVATIVES AS SYK INHIBITORS

A compound of formula (I): or a salt thereof; which is an inhibitor of spleen tyrosine kinase (Syk) and therefore potentially of use in treating diseases resulting from inappropriate activation of mast cells, macrophages, and B-cells and related inflammatory responses and tissue damage, for instance inflammatory disease and/or allergic disorders, and in cancer therapy, specifically heme malignancies, and autoimmune conditions.

SUBSTITUTED PYRIDOPYRAZINES AS NOVEL SYK INHIBITORS

Provided are pyridopyrazine compounds of formula (1), pharmaceutical compositions thereof and methods of use therefore, wherein R1, R2, R3, R4 and m are as defined in the specification.

Substituted Imidazopyridines as HDM2 Inhibitors

The present invention provides substituted imidazopyridines as described herein or a pharmaceutically acceptable salt or solvate thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.

Optimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal Structure Analysis with Human CathepsinL

The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 substituent led to high-affinity ligands with inhibition constants down to 2nM for compounds bearing cyclohexyl substituents. Systematic investigations on the S3 pocket revealed its potential to achieve high activities with aromatic vectors that undergo stacking interactions with the planar peptide backbone forming part of the pocket. X-ray crystal structure analysis with the structurally related enzyme human cathepsinL confirmed the binding mode of the triazine ligand series as proposed by molecular modeling. Sub-micromolar inhibition of the proliferation of cultured parasites was achieved for ligands decorated with the best substituents identified through the optimization cycles. In cell-based assays, the introduction of a basic side chain on the inhibitors resulted in a 35-fold increase in antitrypanosomal activity. Finally, bioisosteric imidazopyridine nitriles were studied in order to prevent off-target effects with unselective nucleophiles by decreasing the inherent electrophilicity of the triazine nitrile headgroup. Using this ligand, the stabilization by intramolecular hydrogen bonding of the thioimidate intermediate, formed upon attack of the catalytic cysteine residue, compensates for the lower reactivity of the headgroup. The imidazopyridine nitrile ligand showed excellent stability toward the thiol nucleophile glutathione in a quantitative invitro assay and fourfold lower cytotoxicity than the parent triazine nitrile.

Structure-activity relationships in Toll-like receptor 7 agonistic 1H-imidazo[4,5-c]pyridines

Engagement of TLR7 in plasmacytoid dendritic cells leads to the induction of IFN-α/β which plays essential functions in the control of adaptive immunity. We had previously examined structure-activity relationships (SAR) in TLR7/8-agonistic imidazoquinolines with a focus on substituents at the N 1, C2, N3 and N4 positions, and we now report SAR on 1H-imidazo[4,5-c]pyridines. 1-Benzyl-2-butyl-1H-imidazo[4,5-c] pyridin-4-amine was found to be a pure TLR7-agonist with negligible activity on TLR8. Increase in potency was observed in N6-substituted analogues, especially in those compounds with electron-rich substituents. Direct aryl-aryl connections at C6 abrogated activity, but TLR7 agonism was reinstated in 6-benzyl and 6-phenethyl analogues. Consistent with the pure TLR7-agonistic behavior, prominent IFN-α induction in human PBMCs was observed with minimal proinflammatory cytokine induction. A benzologue of imidazoquinoline was also synthesized which showed substantial improvements in potency over the parent imidazopyridine. Distinct differences in N6-substituted analogues were observed with respect to IFN-α induction in human PBMCs on the one hand, and CD69 upregulation in lymphocytic subsets, on the other.

FUSED PYRIDINE DERIVATIVES

Fused pyridine derivatives shown as the general formula (I), and their pharmaceutically acceptable salts, stereoisomers or solvates thereof are disclosed, which belong to the technical field of medicines. The R1, R2, R3, Q, X and Y substituents in formula (I) are defined as in the description. Also disclosed are the preparation methods, pharmaceutical compositions comprising the compounds and uses of the compounds in the manufacture of the medicine for the treatment and/or prevention of noninsulin-dependent diabetes, hyperglycemia, hyperlipidemia and insulin resistance.

FUSED PYRIDINE DERIVATIVES

Fused pyridine derivatives shown as the general formula (I), and their pharmaceutically acceptable salts, stereoisomers or solvates thereof are disclosed, which belong to the technical field of medicines. The R1, R2, R3, Q, X and Y substituents in formula (I) are defined as in the description. Also disclosed are the preparation methods, pharmaceutical compositions comprising the compounds and uses of the compounds in the manufacture of the medicine for the treatment and/or prevention of noninsulin-dependent diabetes, hyperglycemia, hyperlipidemia and insulin resistance.