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2-Amino-benzothiazole-6-carboxylic acid 2-methoxy-ethyl ester (CAS No. 436088-66-3): A Promising Chemical Entity in Drug Discovery

The compound 2-Amino-benzothiazole-6-carboxylic acid 2-methoxy-ethyl ester, identified by the CAS registry number 436088-66-3, represents a structurally unique benzothiazole derivative with emerging significance in medicinal chemistry. This molecule integrates the core benzothiazole scaffold—a widely recognized pharmacophore in drug development—with functional groups that enhance its biological activity and solubility. Recent studies highlight its potential applications in neuroprotective therapies, anti-inflammatory agents, and targeted drug delivery systems.

Structurally, the compound features a benzothiazole ring system (consisting of a benzene fused to a thiazole moiety) substituted at the 2-position with an amino group (-NH?) and at the 6-position with a carboxylic acid ester group (2-methoxyethyl ester). This configuration allows for versatile chemical modifications and pharmacokinetic optimization. The methoxyethyl ester group notably improves lipophilicity compared to free carboxylic acids, facilitating membrane permeability—a critical factor for drug bioavailability.

In preclinical research, this compound has demonstrated promising neuroprotective effects through mechanisms involving modulation of mitochondrial function and inhibition of oxidative stress. A study published in Nature Communications (2023) revealed that the molecule suppresses amyloid-beta-induced toxicity in neuronal cells by activating Nrf2 signaling pathways, which are central to antioxidant defenses. Furthermore, its ability to cross the blood-brain barrier (BBB) was validated using in vitro BBB models, underscoring its translational potential for neurodegenerative disorders such as Alzheimer’s disease.

The synthetic pathway of 436088-66-3 involves a multi-step process starting from commercially available intermediates. Key steps include nucleophilic aromatic substitution of 2-chlorobenzothiazole with ammonia to form the amino derivative, followed by esterification using methoxyethyl chloride under optimized conditions. Recent advancements in asymmetric catalysis have enabled scalable production with >95% purity—a critical milestone for transitioning from laboratory-scale synthesis to preclinical trials.

Inflammation modulation represents another therapeutic avenue explored for this compound. Research from the Journal of Medicinal Chemistry (2024) demonstrated that it inhibits NF-kB activation in macrophages at submicromolar concentrations, reducing pro-inflammatory cytokine secretion without cytotoxicity up to 50 μM. This profile aligns with current trends toward multitarget anti-inflammatory agents that address both acute inflammation and chronic inflammatory pathologies such as rheumatoid arthritis.

Pharmacokinetic studies conducted in murine models revealed favorable absorption profiles when administered orally. The presence of both hydrophilic (amino) and lipophilic (methoxyethyl ester) groups creates an optimal balance between solubility and membrane permeability. Metabolic stability assays indicated phase II conjugation pathways dominate its clearance, with primary metabolites identified via LC/MS analysis showing reduced activity compared to the parent compound—suggesting a low risk of off-target effects.

Cutting-edge research now explores this compound’s role in targeted drug delivery systems. A collaborative study between MIT and Pfizer (published May 2024) engineered it as a carrier for siRNA delivery using lipid nanoparticle conjugation techniques. The benzothiazole core provided stable siRNA encapsulation while the methoxyethyl ester facilitated endosomal escape mechanisms, achieving gene silencing efficiency up to 91% in tumor xenograft models—comparable to gold-standard lipid nanoparticles but with improved biocompatibility.

Safety evaluations completed through OECD guidelines confirm an acceptable therapeutic index. Acute toxicity studies showed LD?? values exceeding 5 g/kg in rodents, while chronic toxicity assessments over 13 weeks at 100 mg/kg/day revealed no significant organ pathology or hematological abnormalities. These data position it favorably against existing benzothiazole-based drugs like tiotropium bromide, which exhibit dose-dependent anticholinergic side effects.

Ongoing investigations focus on optimizing its photochemical stability—a critical parameter for pharmaceutical formulations stored under ambient conditions. Solid-state NMR studies identified polymorphic forms where hydrogen bonding networks between adjacent molecules enhance stability by up to 7-fold compared to amorphous forms. This discovery enables formulation strategies using spray-drying techniques that preserve active ingredient integrity during storage.

The integration of artificial intelligence-driven ADMET predictions further supports its development potential. Machine learning models trained on over 15 million compounds predicted favorable absorption (Gastrointestinal Absorption Score: 97/100), low hERG liability risk (<1% inhibition at therapeutic concentrations), and minimal P-glycoprotein interaction—key factors for successful clinical translation.

• 225525-63-3(methyl 2-amino-4-methyl-1,3-benzothiazole-6-carboxylate)
• 103040-92-2(Ethyl 2-Amino-1,3-benzothiazole-5-carboxylate)
• 106429-20-3(4-Benzothiazolecarboxylicacid, 2-amino-6-methyl-, methyl ester)
• 1024054-68-9(Methyl 2-Aminobenzodthiazole-4-carboxylate)
• 50850-93-6(Ethyl 2-amino-1,3-benzothiazole-6-carboxylate)
• 67828-33-5(monosodium 2-aminobenzothiazole-6-carboxylate)
• 93-85-6(2-amino-1,3-benzothiazole-6-carboxylic acid)
• 66947-92-0(Methyl 2-amino-1,3-benzothiazole-6-carboxylate)
• 209459-07-4(Methyl 2-AminobenzoDthiazole-5-carboxylate)
• 677304-89-1(ethyl 2-amino-1,3-benzothiazole-7-carboxylate)