50445-50-6

Usage

InChI:InChI=1/C9H10N2O3/c1-2-10-9(12)7-3-5-8(6-4-7)11(13)14/h3-6H,2H2,1H3,(H,10,12)

Upstream product

• 1037-31-6 4-nitrophenyl 4-nitrobenzoate 
• 75-04-7 ethylamine 
• 62-23-7 4-nitro-benzoic acid 
• 1644630-62-5 C₁₃H₇ClN₂O₆ 
• 100-19-6 (4-nitrophenyl)ethanone 
• 122-04-3 4-nitro-benzoyl chloride 
• 7622-07-3 2,4-dinitrophenyl p-nitrobenzoate 
• 20378-56-7 2-ethyl-3-(4-nitro-phenyl)-oxaziridine 

Downstream Products

• 81617-43-8 N-ethyl-p-nitrobenzimidoyl chloride 
• 51769-82-5 N-acetyl-4-nitrobenzamide 
• 17847-35-7 ethyl[(4-nitrophenyl)methyl]amine 
• 59476-48-1 N-(4-Nitrobenzoyl)-N-ethyl-nitramin 
• 89399-17-7 4-amino-N-ethylbenzamide 

Relevant academic research and scientific papers

Heterocyclic compound as well as preparation method and medical application thereof

The invention relates to a heterocyclic compound suitable for inhibiting or regulating Janus family kinase (JAK), in particular tyrosine kinase 2 (TYK2), a preparation method of the heterocyclic compound and application of the heterocyclic compound in medicine. Specifically, the present invention relates to a compound represented by a general formula (I), a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound or the pharmaceutically acceptable salt thereof, and a method of using the compound or the pharmaceutically acceptable salt thereof to treat and/or prevent Janus kinase-mediated related diseases, especially autoimmune diseases, inflammatory diseases and cancers and a method for preparing the compound or pharmaceutically acceptable salt thereof. The invention also relates to application of the compound or the pharmaceutically acceptable salt thereof or the pharmaceutical composition containing the compound or the pharmaceutically acceptablesalt thereof in preparation of drugs for treating and/or preventing Janus kinase mediated related diseases, especially autoimmune diseases, inflammatory diseases and cancers. Each substituent of thegeneral formula (I) is as defined in the specification.

HETEROCYCLIC COMPOUNDS FOR MEDIATING TYROSINE KINASE 2 ACTIVITY

Heterocyclic compounds shown in Formula (I) suitable for inhibiting or regulating the activity of Janus kinase (JAK), particularly tyrosine kinase 2 (TYK2). The compounds are useful for preventing and/or treating relevant JAK-mediated diseases, such as autoimmune diseases, inflammatory diseases, and cancers.

The α-effect in hydrazinolysis of 4-chloro-2-nitrophenyl x-substituted-benzoates: Effect of substituent x on reaction mechanism and the α-effect

Second-order rate constants (kN) have been measured spectrophotometrically for the reaction of 4-chloro-2- nitrophenyl X-substituted-benzoates (6a-6h) with a series of primary amines including hydrazine in 80 mol % H2O/20 mol % DMSO at 25.0°C. The Bronsted-type plot for the reaction of 4-chloro-2-nitrophenyl benzoate (6d) is linear with βnuc = 0.74 when hydrazine is excluded from the correlation. Such a linear Bronsted-type plot is typical for reactions reported previously to proceed through a stepwise mechanism in which expulsion of the leaving group occurs in the rate-determining step (RDS). The Hammett plots for the reactions of 6a-6h with hydrazine and glycylglycine are nonlinear. In contrast, the Yukawa-Tsuno plots exhibit excellent linear correlations with ?X = 1.29-1.45 and r = 0.53-0.56, indicating that the nonlinear Hammett plots are not due to a change in RDS but are caused by resonance stabilization of the substrates possessing an electron-donating group (EDG). Hydrazine is ca. 47-93 times more reactive than similarly basic glycylglycine toward 6a-6h (e.g., the α-effect). The α-effect increases as the substituent X in the benzoyl moiety becomes a stronger electronwithdrawing group (EWG), indicating that destabilization of the ground state (GS) of hydrazine through the repulsion between the nonbonding electron pairs on the two N atoms is not solely responsible for the substituent-dependent α-effect. Stabilization of transition state (TS) through five-membered cyclic TSs, which would increase the electrophilicity of the reaction center or the nucleofugality of the leaving group, contributes to the α-effect observed in this study.

The conversion of aryl and heteroaryl methylketones to the corresponding secondary or tertiary amides

Secondary or tertiary amides have been prepared directly from aryl, heteroaryl methyl ketones using an iodineamine-NaOH system which afforded the expected products in good yields in an aqueous medium. The present method has the advantages of using inexpensive reagents, mild reaction condition and ease of manipulation.

Effects of amine nature and nonleaving group substituents on rate and mechanism in aminolyses of 2,4-dinitrophenyl x-substituted benzoates

Second-order rate constants have been measured for the reactions of 2,4-dinitrophenyl X-substituted benzoates (1a-f) with a series of primary amines in 80 mol % H2O/20 mol % DMSO at 25.0 ± 0.1 °C. The Bronsted-type plot for the reactions of 1d with primary amines is biphasic with slopes β1 = 0.36 at the high pKa region and β2 = 0.78 at the low pKa region and the curvature center at pKa° = 9.2, indicating that the reaction proceeds through an addition intermediate with a change in the rate-determining step as the basicity of amines increases. The corresponding Bro nsted-type plot for the reactions with secondary amines is also biphasic with β1 = 0.34, β2 = 0.74, and pKa° = 9.1, indicating that the effect of amine nature on the reaction mechanism and pKa° is insignificant. However, primary amines have been found to be less reactive than isobasic secondary amines. The microscopic rate constants associated with the aminolysis have revealed that the smaller k 1 for the reactions with primary amines is fully responsible for their lower reactivity. The electron-donating substituent in the nonleaving group exhibits a negative deviation from the Hammett plots for the reactions of 1a-f with primary and secondary amines, while the corresponding Yukawa-Tsuno plots are linear. The negative deviation has been ascribed to stabilization of the ground state of the substrate through resonance interaction between the electron-donating substituent and the carbonyl functionality.

A rapid and convenient synthesis of amides from aromatic acids and aliphatic amines in dry media under microwave irradiation

The synthesis of amides 2 from the corresponding aromatic acids and aliphatic amines in the presence of catalytic amount of p-toluenesulfonic acid has been reported. The reactions are accelerated with microwave irradiation under solvent-free conditions to afford a high yielding synthesis of amides.

Kinetic stability of novel nitrile ylides

A series of relatively stable novel trifluoromethyl substituted nitrile ylides have been generated by base promoted elimination of hydrogen chloride from the corresponding imidoyl chlorides in acetonitrile and aqueous dioxane solution at 25 °C. The format

An unusual ground-state stabilization effect and origins of the α- effect in aminolyses of Y-substituted phenyl X-substituted benzoates

Second-order rate constants have been measured spectrophotometrically for the reactions of X-C6H4CO2C6H4-Y with a series of primary amines in H2O containing 20 mol% DMSO at 25.0 ± 0.1°C. The reactivity increases as the substituent (X and Y) becomes a stronger electron-withdrawing group. The σ+ constants give better Hammett correlation than σ constants for the reactions of 4-nitrophenyl X-substituted benzoates with glycylglycine (glygly) and hydrazine (NH2NH2), indicating that the ground-state stabilization effect is unusually significant on the reaction rates. The reactions of X-C6H4CO2C6H4-Y with glygly and NH2NH2 appear to proceed through the same mechanism, but the degree of leaving-group departure and the negative charge developed in the acyl moiety at the rate-determining TS is considered to be more significant for the glygly system than the NH2NH2 system based on β(1g) and ρ(x) values. The magnitude of the α-effect is observed to be not always dependent on the β(nuc) value but dependent on the electronic nature of the substituent X and Y, i.e., an electron-donating substituent increases the α-effect, while an electron-withdrawing one decreases the α-effect. The present study has led to the conclusion that the ground-state effect is important for the reaction rates but it is not solely responsible for the α-effect, and the intramolecular H-bonding interactions (4) are proposed for the cause of the increasing or decreasing α-effect trends observed in the present system.

Metalloporphyrin-promoted rearrangement of 2-alkyloxaziridines

Transformation of 2-alkyloxaziridines to the corresponding amides is efficiently catalyzed by high-valent metalloporphyrins. This novel rearrangement was used to create a peptide bond and the precursor of a dipeptide ''aspartame'' was obtained in good yield.

Anticonvulsant activity of some 4-aminobenzamides

A series of 4-aminobenzamides of some simple primary and secondary amines were prepared and evaluated for anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole (metrazole) and in the rotorod assay for neurologic deficit. For those N-alkyl amides tested, 4-amino-N-amylbenzamide was the most potent against maximal electroshock seizures (MES): ED50=42.98 mg/kg; however, the N-cyclohexylbenzamide showed the greatest protective index (PI=TD50/ED50), 2.8. The introduction of a second aromatic ring produced more potent compounds, with d,l-4-amino-N-(α-methylbenzyl)-benzamide showing the highest level of activity. This compound has an anti-MES ED50 of 18.02 mg/kg in mice when administered intraperitoneally (ip) and a TD50 of 170.78 mg/kg (PI=9.5) in the same species. These data compare quite favorably with those for phenobarbital and phenytoin in the same assays.