22244-22-0

Usage

Uses

Used in Pharmaceutical Industry:
3,4-Dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid ethyl ester is used as an antidepressant medication for the treatment of major depressive disorder, generalized anxiety disorder, panic disorder, and other related conditions. Its ability to selectively inhibit serotonin reuptake helps in regulating mood and reducing anxiety levels, making it a popular choice for patients suffering from mood and anxiety disorders.
Used in Research and Development:
Escitalopram is also utilized in research and development for studying the effects of serotonin on mood regulation and anxiety. Its selective action on serotonin reuptake provides valuable insights into the role of neurotransmitters in mental health and the development of novel therapeutic agents for the treatment of mood and anxiety disorders.
Used in Drug Formulation:
The ethyl ester form of 3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid enhances the compound's bioavailability and distribution in the body, making it an essential component in the formulation of various antidepressant medications. This improved pharmacokinetic profile allows for more effective treatment of mood and anxiety disorders with better patient compliance and reduced side effects.

InChI:InChI=1/C11H13NO3/c1-2-14-11(13)10-7-12-8-5-3-4-6-9(8)15-10/h3-6,10,12H,2,7H2,1H3

Upstream product

• 95-55-6 2-amino-phenol 
• 3674-13-3 2,3-dibromopropionic acid ethyl ester 
• 79-16-3 N-methyl-acetamide 
• 88-75-5 2-hydroxynitrobenzene 
• 177202-60-7 ethyl 3,4-dihydro-2H-benzo [b][1,4]oxazine-3-carboxylate 

Downstream Products

• 68466-11-5 ethyl 4-benzoyl-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate 
• 13582-93-9 3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamide 
• 68281-42-5 ethyl 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylate 
• 82756-74-9 (3,4-dihydro-2H-benzo[1,4]oxazin-2-yl)-methanol 
• 91842-95-4 3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid methylamide 
• 177202-61-8 ethyl 4-benzyloxycarbonyl-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate 
• 220120-55-8 ethyl 4-[3-(benzyloxycarbonyl)propanoyl]-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate 
• 534574-32-8 benzyl 3-[2-(ethoxycarbonyl)-3,4-dihydro-1,4-benzoxazin-4-yl]-3-oxopropanoate 
• 391873-71-5 ethyl 4-benzyl-7-formyl-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate 
• 212578-42-2 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxamide 
• 176383-64-5 4-benzyl-3,4-dihydro-2H-1,4-benzoxazine-2-carbaldehyde 
• 212578-39-7 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylic acid 
• 212578-41-1 2-{N-[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl}-4-methyl-3,4-dihydro-2H-1,4-benzoxazine 
• 1027148-11-3 [4-(4-Fluoro-phenyl)-piperazin-1-yl]-(4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-2-yl)-methanone 

Relevant academic research and scientific papers

A Novel M1 PAM VU0486846 Exerts Efficacy in Cognition Models without Displaying Agonist Activity or Cholinergic Toxicity

Selective activation of the M1 subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M1 ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M1, leading to agonist actions in the prefrontal cortex (PFC) that impair cognitive function, induce behavioral convulsions, and result in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M1 PAM, VU0486846. VU0486846 possesses only weak agonist activity in M1-expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427, and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [3H]-NMS binding at the orthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M1 PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M1 PAM activity (EC50 > 100 nM) and pure-PAM activity in native tissues display robust procognitive efficacy without AEs mediated by excessive activation of M1. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.

The discovery of VU0486846: steep SAR from a series of M1 PAMs based on a novel benzomorpholine core

This letter describes the chemical optimization of a new series of M1 positive allosteric modulators (PAMs) based on a novel benzomorpholine core, developed via iterative parallel synthesis, and culminating in the highly utilized rodent in vivo tool compound, VU0486846 (7), devoid of adverse effect liability. This is the first report of the optimization campaign (SAR and DMPK profiling) that led to the discovery of VU0486846 and details all of the challenges faced in allosteric modulator programs (both steep and flat SAR, as well as subtle structural changes affecting CNS penetration and overall physiochemical and DMPK properties).

Multigram-scale HPLC enantioseparation as a rescue pathway for circumventing racemization problem during enantioselective synthesis of ethyl 3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate

Racemic ethyl 3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate is a key synthon for the design of promising therapeutic drugs. It is mainly synthesized from racemic ethyl 2,3-dibromopropionate and 2-aminophenol in presence of K2CO3 in refluxed acetone. Unfortunately, synthesis of (R)- and (S)-enantiomers using the enantioselective version of this reaction, which should normally be performed with a double SN2 mechanism, is unsuitable due to a racemization process involving the dehydrobromination of enantiopure ethyl 2,3-dibromopropionate into ethyl 2-bromoacrylate. For the first time, the enantioselective version is studied (ee ≈ 55–66%), and the percentage of racemization process has estimated to around 34–46% after determination of the optimal experimental conditions for analytical HPLC enantioseparation of racemate. The influence of the experimental and purification conditions on the racemization rate is also studied. The results indicate that racemization occurs faster at the beginning of the reaction but the initiation of the double SN2 process takes place more faster to limit the racemization rate. The study of the influence of experimental conditions (reaction times, temperature, solvent or type of base, etc.) on the degree of racemization of the (R)- enantiomer is performed and shows that despite changes in the experimental conditions, the synthesis of the (R)- enantiomer is always accompanied by a racemization rate which is difficult in reducing. In parallel, (R)- and (S)-enantiomers are obtained in high enantiopurity (ee > 99.5%) by preparative HPLC enantioseparation of racemate on multigram scale and characterized by optical rotation measurements, ECD and UV spectra.

Discovery of Dihydro-1,4-Benzoxazine Carboxamides as Potent and Highly Selective Inhibitors of Sirtuin-1

Sirtuins are signaling hubs orchestrating the cellular response to various stressors with roles in all major civilization diseases. Sirtuins remove acyl groups from lysine residues of proteins, thereby controlling their activity, turnover, and localization. The seven human sirtuins, SirT1-7, are closely related in structure, hindering the development of specific inhibitors. Screening 170,000 compounds, we identify and optimize SirT1-specific benzoxazine inhibitors, Sosbo, which rival the efficiency and surpass the selectivity of selisistat (EX527). The compounds inhibit the deacetylation of p53 in cultured cells, demonstrating their ability to permeate biological membranes. Kinetic analysis of inhibition and docking studies reveal that the inhibitors bind to a complex of SirT1 and nicotinamide adenine dinucleotide, similar to selisistat. These new SirT1 inhibitors are valuable alternatives to selisistat in biochemical and cell biological studies. Their greater selectivity may allow the development of better targeted drugs to combat SirT1 activity in diseases such as cancer, Huntington's chorea, or anorexia.

5-AMINO-4-CARBAMOYL-PYRAZOLE COMPOUNDS AS SELECTIVE AND IRREVERSIBLE T790M OVER WT-EGFR KINASE INHIBITORS AND USE THEREOF????

Disclosed are compounds of Formula (I), pharmaceutical compositions comprising the same, processes for the preparation thereof, and the use thereof.

SUBSTITUTED 4-BENZYL-3,4-DIHYDRO-2H-BENZO[B][1,4]OXAZINE-2CARBOXAMIDE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF MUSCARINIC ACETYCHOLINE RECEPTOR M1

In one aspect, the invention relates to N-substituted 3,4-dihydro-benzo[￡][l,4]oxazine-2-carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1

SUBSTITUTED 3,4-DIHYDRO-2H-BENZO[B] [1,4]OXAZINE COMPOUNDS AS CALCIUM SENSING RECEPTOR MODULATORS

The present invention provides calcium sensing receptor modulators (CaSR). In particular, the compounds described herein are useful for treating, managing, and/or lessening the severity of diseases, disorders, syndromes and/or conditions associated with t

A COMPOUND FOR INHIBITING HUMAN 11-β-HYDROXY STEROID DEHYDROGENASE TYPE 1, AND A PHARMACEUTICAL COMPOSITION COMPRISING THE SAME

The present invention relates to a novel compound, or a stereoisomer, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition for human-11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) comprising the same. The invention provides a compound, which has excellent activity and solubility and is more efficiently formulated and delivered, and a pharmaceutical composition for human-11-beta-hydroxysteroid dehydrogenase type 1 comprising the same.

BENZO [B] [1, 4] OXAZIN DERIVATIVES AS CALCIUM SENSING RECEPTOR MODULATORS

Compounds of Formula (I) along with processes for their preparation that are useful for treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of calcium sensing (Ca SR) receptors. Methods of treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of calcium sensing (Ca SR) receptors of Formula (I).

BETA-SECRETASE MODULATORS AND METHODS OF USE

The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A, B, R3, R4, R5, i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula I, methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula I, or compositions including them, to a subject. The invention also comprises further embodiments of Formulas II and III, intermediates and processes useful for the preparation of compounds of the invention.