53696-52-9

Upstream product

• 5279-61-8 N-methyl-4-(4-nitrophenyl)formamide 
• 100-01-6 4-nitro-aniline 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 100-15-2 N-methyl(p-nitroaniline) 
• 75-44-5 phosgene 

Downstream Products

• 108668-99-1 methyl-(4-nitro-phenyl)-peroxycarbamic acid tert-butyl ester 
• 1235712-73-8 3,4-dibutyl-1-methyl-6-nitroquinolin-2(1H)-one 
• 1039976-40-3 1-(4-aminophenyl)-1-methyl-3-phenylurea 
• 1392278-31-7 GN-6860 
• 1392278-32-8 GN-6958 
• 86504-26-9 C₁₄H₁₃N₃O₃ 
• 103640-04-6 O-tert-butyl-N-methyl-N-(4-nitro-phenyl)-hydroxylamine 
• 246237-03-6 5-[(4-nitrophenyl)methylcarbamoyloxy]-3-hydroxy-3-methylpentanoic acid 
• 246237-14-9 (S)-(4-nitrophenyl)methylcarbamic acid 3-hydroxy-3-methyl-5-oxopentyl ester 
• 246236-98-6 (4-nitrophenyl)methylcarbamic acid 3-hydroxy-3-methyl-5-oxopentyl ester 
• 246237-00-3 methyl-(4-nitro-phenyl)-carbamic acid 3-hydroxy-3-methyl-hex-5-enyl ester 
• 100-15-2 N-methyl(p-nitroaniline) 

Relevant academic research and scientific papers

Self-Immolative System for Disclosure of Reactive Electrophilic Alkylating Agents: Understanding the Role of the Reporter Group

The development of stable, efficient chemoselective self-immolative systems, for use in applications such as sensors, requires the optimization of the reactivity and degradation characteristics of the self-immolative unit. In this paper, we describe the effect that the structure of the reporter group has upon the self-immolative efficacy of a prototype system designed for the disclosure of electrophilic alkylating agents. The amine of the reporter group (a nitroaniline unit) was a constituent part of a carbamate that functioned as the self-immolative unit. The number and position of substituents on the nitroaniline unit were found to play a key role in the rate of self-immolative degradation and release of the reporter group. The position of the nitro substituent (meta- vs para-) and the methyl groups in the ortho-position relative to the carbamate exhibited an influence on the rate of elimination and stability of the self-immolative system. The ortho-methyl substituents imparted a twist on the N-C (aromatic) bond leading to increased resonance of the amine nitrogen's lone pair into the carbonyl moiety and a decrease of the leaving character of the carbamate group; concomitantly, this may also make it a less electron-withdrawing group and lead to less acidification of the eliminated β-hydrogen.

Self-immolative systems for the disclosure of reactive electrophilic alkylating agents

In this paper we report the design, synthesis and assessment of the first examples of self-immolative systems triggered by non-acidic electrophilic agents such as methyl, allyl or benzylic halides. These systems provide a visual colorimetric disclosure response upon exposure to these electrophilic reagents under mild, basic conditions without the need for the use of analytical instrumentation.

Optimization of 1,2,5-thiadiazole carbamates as potent and selective ABHD6 inhibitors

At present, inhibitors of α/β-hydrolase domain 6 (ABHD6) are viewed as a promising approach to treat inflammation and metabolic disorders. This article describes the development of 1,2,5-thiadiazole carbamates as ABHD6 inhibitors. Altogether, 34 compounds were synthesized, and their inhibitory activity was tested using lysates of HEK293 cells transiently expressing human ABHD6 (hABHD6). Among the compound series, 4-morpholino-1,2,5-thiadiazol-3-yl cyclooctyl(methyl)carbamate (JZP-430) potently and irreversibly inhibited hABHD6 (IC50 = 44 nM) and showed ～ 230-fold selectivity over fatty acid amide hydrolase (FAAH) and lysosomal acid lipase (LAL), the main off-targets of related compounds. Additionally, activity-based protein profiling indicated that JZP-430 displays good selectivity among the serine hydrolases of the mouse brain membrane proteome. JZP-430 has been identified as a highly selective, irreversible inhibitor of hABHD6, which may provide a novel approach in the treatment of obesity and type II diabetes.

Discovery of 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivatives as non-peptidic selective SUMO-sentrin specific protease (SENP)1 inhibitors

We developed 1-[4-(N-benzylamino)phenyl]-3-phenylurea derivative 4 (GN6958) as a non-peptidic selective SUMO-sentrin specific protease (SENP)1 protease inhibitor based on the hypoxia inducible factor (HIF)-1α inhibitor 1 (GN6767). The direct interaction of compound 1 with SENP1 protein in cells was observed by the pull-down experiments using the biotin-tagged compound 2 coated on the streptavidin affinity column. Among the various 1-[4-(N-benzylamino) phenyl]-3-phenylurea derivatives tested, compounds 3 and 4 suppressed HIF-1α accumulation in a concentration-dependent manner without affecting the expression level of tubulin protein in HeLa cells. Both compounds inhibited SENP1 protease activity in a concentration-dependent manner, and compound 4 exhibited more potent inhibition than compound 3. Compound 4 exhibited selective inhibition against SENP1 protease activity without inhibiting other protease enzyme activities in vitro.

Iridium-catalyzed annulation of N -arylcarbamoyl chlorides with internal alkynes

An iridium complex successfully catalyzed the annulation of various N-arylcarbamoyl chlorides with internal alkynes to afford 2-quinolones in good to excellent yields. The present reaction is widely applicable to substrates with various functionalities. An amide-iridacycle complex was isolated, and it is likely that such an iridacycle species is a key intermediate in the catalytic reaction.

Structure-reactivity relationships in the pyridinolysis of N-methyl-N-arylcarbamoyl chlorides in dimethyl sulfoxide

Nucleophilic substitution reactions of N-methyl-N-arylcarbamoyl chlorides (YC6H4N(CH3)COCl) with pyridines (XC5H4N) have been investigated in dimethyl sulfoxide at 45.0 °C. A striking trend in the selectivity parameters is that they are constant within experimental errors, ρX = -2.25 ± 0.03, βX = 0.42 ± 0.01, and ρX = 1.10 ± 0.06, with changing reactivities of the electrophiles (6δσY) and nucleophiles (δσX), respectively, and this leads to a vanishingly small cross-interaction constant, ρXY βXY 0. The rate data can be expressed in the Ritchie N+ type equation. Based on this and other results, the mechanism of nucleophile (pyridine) addition to the resonance- stabilized carbocation is proposed. It has been shown from the definition βXY (and ρXY) together with the Marcus equation that the high intrinsic barrier, ΔG±, in the intrinsic-barrier controlled reaction series is a prerequisite for such reactions in which the cross-interaction vanishes and the N+ relationship holds.

A catalytic enantioselective route to hydroxy-substituted quaternary carbon centers: Resolution of tertiary aldols with a catalytic antibody

Aldolase antibody 38C2-catalyzed resolutions of tertiary aldols were studied. Tertiary aldols proved to be very good substrates for antibody catalyzed retro-aldol reactions. The catalytic proficiency, (k(cat)/K(M))/k(uncat), of the antibody for these reactions was on the order of 1010 M-1. A fluorogenic tertiary aldol allowed for the quantitative study of enantiomeric excess as a function of reaction conversion, revealing an E value of ca. 160 in this case. Study of a variety of substrates demonstrated that antibody-catalyzed retro-aldolization provides rapid entry to highly enantiomerically enriched tertiary aldols, typically > 95% ee, containing structurally varied, heteroatom-substituted quaternary carbon centers. The utility of this approach to natural product syntheses has been demonstrated with the syntheses of (+)-frontalin, the side chain of Saframycin H, and formal syntheses of (+)- and (-)-mevalonolactone.

Umpoled Vilsmeier reagents. The chemistry of aminochlorocarbenes derived from Vilsmeier reagents by the action of bases

Vilsmeier reagents such as N-methyl-N-phenylchloroiminium chloride are readily deprotonated by tert-amines even in POCl3 solution. The resulting transient intermediates, aminochlorocarbenes, are nucleophilic (i.e. umpoled Vilsmeier reagents) and are trapped with electrophiles. In this way dimers [1,2-bis(N-methylanilino)-1,2-dichloroethanes] 3, 'trimers' (indolo[3,2-b]quinolininium chlorides) 4 and 5, 'tetramers' (2,2′-bis-indoles) 11 and isatins 9 and 10 are accessible in one-pot processes from the formanilide.

Carbenes from Vilsmeier reagents by the action of bases in POCl3; The umpolung of Vilsmeier reagents

When para-substituted N-methylformanilides are treated in POCl3 with a base, the corresponding Vilsmeier reagent formed undergoes ready deprotonation to give an amino-chlorocarbene from which a range of products derive; a carba- moyl chloride, N-methylisatins, dimers ? [1,2-dichloro-1,2- bis(N-methyl-N-arylamino)ethenes], trimers ? [5,10-dimethyl- 11-(N-methyl-N-arylamino)-10H-indolo[3,2-b]quinolinium and 5,10-dimethyl-10H-indolo[3,2-b]quinolinium salts] and tetramers ? [1,1′-dimethyl-3,3′-bis(N-methyl-N-arylamino)-2,2-biindolyl] are isolated, depending upon the base used and the para-substituent.