15855-06-8

Basic information

• Product Name: 2-Chloro-6-methoxyisonicotinic acid
• Synonyms: 2-Chloro-6-methoxy-4-pyridinecarboxylic acid;2-Chloro-6-methoxypyridine-4-c;2-Chloro-6-methoxypyridine-4-carboxylic acid, 4-Carboxy-2-chloro-6-methoxypyridine;TIMTEC-BB SBB005427;2-CHLORO-6-METHOXYISONICOTINIC ACID;2-CHLORO-6-METHOXYPYRIDINE-4-CARBOXYLIC ACID;BUTTPARK 43\57-34
• CAS NO: 15855-06-8
• Molecular Formula: C₇H₆ClNO₃
• Molecular Weight: 187.58
• Product Categories: Carboxylic Acids;Pyridines;Carboxylic Acids
• Mol File: 15855-06-8.mol

Chemical Properties

• Melting Point: 214 °C
• Boiling Point: 209-213℃
• Flash Point: 201.1 °C
• Appearance: /
• Density: 1.43g/cm³
• Vapor Pressure: 2.03E-07mmHg at 25°C
• Refractive Index: 1.567
• PKA: 2.88±0.10(Predicted)
• CAS DataBase Reference: 2-Chloro-6-methoxyisonicotinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-6-methoxyisonicotinic acid(15855-06-8)
• EPA Substance Registry System: 2-Chloro-6-methoxyisonicotinic acid(15855-06-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36/37/39-37/39-36/37
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 15855-06-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-Chloro-6-methoxyisonicotinic acid is used as an intermediate in the synthesis of various pharmaceuticals. Its unique structure and functional groups make it a valuable building block for the development of new drugs with potential therapeutic applications.
Used in Agrochemical Industry:
In the agrochemical sector, 2-Chloro-6-methoxyisonicotinic acid serves as a key component in the production of various agrochemicals. Its incorporation into these compounds can enhance their effectiveness in pest control, crop protection, and other agricultural applications.
Used in Organic Synthesis:
2-Chloro-6-methoxyisonicotinic acid is utilized as a versatile starting material in organic synthesis. Its reactivity and functional groups allow for the formation of a wide range of organic compounds, making it a valuable asset in the synthesis of various chemical products.
Used in Research and Development:
2-Chloro-6-methoxyisonicotinic acid is also employed in research and development settings, where its unique properties and potential applications are explored. Scientists and researchers use 2-Chloro-6-methoxyisonicotinic acid to investigate new chemical reactions, develop novel compounds, and study its interactions with other molecules.

InChI:InChI=1/C7H6ClNO3/c1-12-6-3-4(7(10)11)2-5(8)9-6/h2-3H,1H3,(H,10,11)

Upstream product

• 99-11-6 citrazinic acid 
• 67-56-1 methanol 
• 5398-44-7 2,6-dichloropyridine-4-carboxylic acid 
• 99-11-6 citrazinic acid 
• 124-41-4 sodium methylate 

Downstream Products

• 106719-08-8 Ethyl 6-chloro-2-methoxy-pyridine-4-carboxylate 
• 105596-63-2 2-methoxy-isonicotinic acid 
• 478946-88-2 4-((S)-2-Benzyloxycarbonylamino-2-carboxy-ethyl)-6-methoxy-pyridine-2-carboxylic acid 
• 308357-98-4 (+)-methyl N-(benzyloxycarbonyl)-3-(n-propyloxycarbonyl-6-methoxy-4-pyridinyl)-L-alaninate 
• 478946-79-1 n-propyl 4-(bromomethyl)-6-methoxy-2-pyridinecarboxylate 
• 105596-61-0 ethyl 2-methoxy-pyridine-4-carboxylate 
• 1402738-51-5 2-chloro-6-methoxy-4-(methoxymethyl)pyridine 
• 864674-09-9 1-(2-chloro-6-methoxypyridin-4-yl)ethanone 
• 1282042-12-9 C₁₈H₁₈N₄O₂ 
• 1282042-11-8 C₁₉H₂₀N₄O₂ 
• 1282042-10-7 C₁₉H₂₀N₄O₂ 
• 1282042-09-4 C₁₉H₂₀N₄O₂ 
• 1282042-08-3 C₁₈H₁₈N₄O 
• 1282042-20-9 C₂₁H₂₂N₄O₃ 

Relevant articles and documents

Potent colchicine-site ligands with improved intrinsic solubility by replacement of the 3,4,5-trimethoxyphenyl ring with a 2-methylsulfanyl-6-methoxypyridine ring

Colchicine site antimitotic agents typically suffer from low aqueous solubilities and are formulated as phosphate prodrugs of phenolic groups. These hydroxyl groups are the aim of metabolic transformations leading to resistance. There is an urgent need for more intrinsically soluble analogues lacking these hydroxyl groups. The 3,4,5-trimethoxyphenyl ring of combretastatin A-4 is a liability in terms of solubility but it is considered essential for high cytotoxic and tubulin polymerization inhibitory (TPI) activity. We have synthesized 36 new analogues of combretastatin A-4 replacing the trimethoxyphenyl moiety with more polar pyridine based moieties, measured their aqueous solubility, and studied their anti-proliferative effects against 3 human cancer cell lines. We show here that pyridine rings can be successful replacements for the trimethoxyphenyl ring, resulting in potent and more soluble analogues. The more straightforward replacement, a 2,6-dimethoxypyridine ring led to inactive analogues, but a 2-methoxy-6-methylsulfanylpyridine moiety led to active analogues when combined with different B rings. This replacement led to potent cytotoxic activity against sensitive human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies. Cell cycle analysis also showed apoptotic responses following treatment. Docking studies suggested binding at the colchicine site of tubulin and provided a good agreement with the observed SAR. A 2-methoxy-6-methylsulfanylpyridine moiety is a good trimethoxyphenyl ring replacement for the development of new colchicine site ligands.

Novel 5-fluorouracil sensitizers for colorectal cancer therapy: Design and synthesis of S1P receptor 2 (S1PR2) antagonists

Sphingosine-1-phosphate receptor 2 (S1PR2) has been identified as a brand-new GPCR target for designing antagonists to reverse 5-FU resistance. We herein report the structural optimization and structure-activity relationship of JTE-013 derivatives as S1PR2 antagonists. Compound 9d was the most potent S1PR2 antagonist (KD = 34.8 nM) among developed compounds. Here, compound 9d could significantly inhibit the expression of dihydropyrimidine dehydrogenase (DPD) to reverse 5-FU-resistance in HCT116DPD and SW620/5-FU cells. Further mechanism studies demonstrated that compound 9d not only inhibited S1PR2 but also affected the transcription of S1PR2. In addition, compound 9d also showed acceptable selectivity to normal cells (NCM460). Importantly, compound 9d with suitable pharmacokinetic properties could significantly reverse 5-FU-resistance in the HCT116DPD and SW620/5-FU xenograft models without obvious toxicity, in which the inhibition rates of 5-FU were increased from 23.97% to 65.29% and 27.23% to 60.81%, respectively. Further immunohistochemistry and western blotting analysis also demonstrated that compound 9d significantly decreases the expression of DPD in tumor and liver tissues. These results indicated that compound 9d is a promising lead compound to reverse 5-FU-resistance for colorectal cancer therapy.

COMPOUNDS AND METHODS OF USE

Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X1, X2, X3, X4, X5, A, L, R1, R2, R5, m and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

Compounds and methods of use

Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X1, X2, X3, X4, Y, A, L1, L2, R1, R2, R5, m and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

Design, synthesis and biological evaluation of sphingosine-1-phosphate receptor 2 antagonists as potent 5-FU-resistance reversal agents for the treatment of colorectal cancer

5-Fluorouracil (5-FU) and its prodrugs are the essential clinical drugs for colorectal cancer (CRC) treatment. However, the drug resistance of 5-FU has caused high mortality of CRC patients. Thus, it is urgent to develop reversal agents of 5-FU resistance. Sphingosine-1-phosphate receptor 2 (S1PR2) was proved to be a potential target for reversing 5-FU resistance, but the activity of known S1PR2 antagonists JTE-013 were weak in 5-FU-resistant cell lines. To develop more potent S1PR2 antagonists to treat 5-FU-resistant cancer, a series of JTE-013 derivatives were designed and synthesized. The most promising compound 40 could markedly reverse the resistance in 5-FU-resistant HCT116 cells and 5-FU-resistant SW620 cells via inhibiting the expression of dihydropyrimidine dehydrogenase (DPD). The key was that compound 40 with improved pharmacokinetic properties significantly increased the inhibitory rate of 5-FU in the SW620/5-FU cells xenograft model with no observable toxicity by inhibiting the expression of DPD in tumor and liver tissues. Altogether, these results suggest that compound 40 may be a promising drug candidate to reverse 5-FU resistance in the treatment of CRC.

Optimizing the Benefit/Risk of Acetyl-CoA Carboxylase Inhibitors through Liver Targeting

Preclinical and clinical data suggest that acetyl-CoA carboxylase (ACC) inhibitors have the potential to rebalance disordered lipid metabolism, leading to improvements in nonalcoholic steatohepatitis (NASH). Consistent with these observations, first-in-human clinical trials with our ACC inhibitor PF-05175157 led to robust reduction of de novo lipogenesis (DNL), albeit with concomitant reductions in platelet count, which were attributed to the inhibition of fatty acid synthesis within bone marrow. Herein, we describe the design, synthesis, and evaluation of carboxylic acid-based ACC inhibitors with organic anion transporting polypeptide (OATP) substrate properties, which facilitated selective distribution of the compounds at the therapeutic site of action (liver) relative to the periphery. These efforts led to the discovery of clinical candidate PF-05221304 (12), which selectively inhibits liver DNL in animals, while demonstrating considerable safety margins against platelet reduction in a nonhuman primate model.

Discovery of a Class of Potent and Selective Non-competitive Sentrin-Specific Protease 1 Inhibitors

Sentrin-specific proteases (SENPs) are responsible for the maturation of small ubiquitin-like modifiers (SUMOs) and the deconjugation of SUMOs from their substrate proteins. Studies on prostate cancer revealed an overexpression of SENP1, which promotes prostate cancer progression as well as metastasis. Therefore, SENP1 has been identified as a novel drug target against prostate cancer. Herein, we report the discovery and biological evaluation of potent and selective SENP1 inhibitors. A structure-activity relationship (SAR) of the newly identified pyridone scaffold revealed allosteric inhibitors with very attractive in vitro ADMET properties regarding plasma binding and plasma stability for this challenging target. This study also emphasizes the importance of biochemical mode of inhibition studies for de novo designed inhibitors.

TBAJ-876, a 3,5-dialkoxypyridine analogue of bedaquiline, is active against Mycobacterium abscessus

Lung disease caused by Mycobacterium abscessus is very difficult to cure, and treatment failure rates are high. The antituberculosis drug bedaquiline (BDQ) is used as salvage therapy against this dreadful disease. However, BDQ is highly lipophilic, displays a long terminal half-life, and presents a cardiotoxicity liability associated with QT interval prolongation. Recent medicinal chemistry campaigns resulted in the discovery of 3,5-dialkoxypyridine analogues of BDQ which are less lipophilic, have higher clearance, and display lower cardiotoxic potential. TBAJ-876, a clinical development candidate of this series, shows attractive in vitro antitubercular activity and efficacy in a murine tuberculosis model. Here, we asked whether TBAJ-876 is active against M. abscessus. TBAJ-876 displayed submicromolar in vitro activity against reference strains representing the three subspecies of M. abscessus and against a collection of clinical isolates. Drug-drug potency interaction studies with commonly used anti-M. abscessus antibiotics showed no antagonistic effects, suggesting that TBAJ-876 could be coadministered with currently used drugs. Efficacy studies, employing a mouse model of M. abscessus infection, demonstrated potent activity in vivo. In summary, we demonstrate that TBAJ-876 shows attractive in vitro and in vivo activities against M. abscessus, similar to its BDQ parent. This suggests that next-generation BDQ, with improved tolerability and pharmacological profiles, may be useful for the treatment of M. abscessus lung disease in addition to the treatment of tuberculosis.

2-METHOXY-PYRIDIN-4-YL-DERIVATIVES

The invention relates to pyridine derivatives of Formula (I) wherein A, R1, R2, R3, and R4 are as described in the description, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.

2-METHOXY-PYRIDIN-4-YL DERIVATIVES

The invention relates to pyridine derivatives of Formula (I) wherein A, R1, R2, R3, and R4 are as described in the description, their preparation and their use as pharmaceutically active compounds. Said compounds particularly act as immunomodulating agents.