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Chayka, Artem ; Danda, Matěj ; Dostálková, Alžběta ; Spiwok, Vojtěch ; Klimešová, Anna ; Kapisheva, Marina , et al.

Abstract: The use of Fpocket and virtual screening techniques enabled us to identify potential allosteric druggable pockets within the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Of the compounds screened, compound 1 was identified as a promising inhibitor, lowering a SARS-CoV-2 RdRp activity to 57% in an enzymatic assay at 10 µM concentration. The structure of compound 1 was subsequently optimized in order to preserve or enhance inhibitory activity. This involved the substitution of problematic and aromatic nitro groups with more inert functionalities. The scaffold with two NH groups was identified as essential for the compound's activity but also exhibited high toxicity in Calu-3 cells. To address this issue, a scaffold hopping approach was employed to replace the urea core with potentially less toxic urea isosteres. This approach yielded several structural analogues with notable activity, specifically 2,2’-bisimidazol (in compound 55 with residual activity = 42%) and (1H-imidazol-2-yl)urea (in compounds 59 and 60, with = 50 and 28%, respectively). Despite these advances, toxicity remained a major concern. These compounds represent a promising starting point for further structure-activity relationship studies of allosteric inhibitors of SARS-CoV-2 RdRp, with the goal of reducing their cytotoxicity and improving aqueous solubility.

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Jang, Mingyeong ; Lim, Taeho ; Park, Byoung Yong ; Han, Min Su ;

Abstract: In this study, we developed a metal-free and highly chemoselective method for the reduction of aromatic nitro compounds. This reduction was performed using tetrahydroxydiboron [B2(OH)4] as the reductant and 4,4'-bipyridine as the organocatalyst and could be completed within 5 min at room temperature. Under optimal conditions, nitroarenes with sensitive functional groups, such as vinyl, ethynyl, carbonyl, and halogen, were converted into the corresponding anilines with excellent selectivity while avoiding the undesirable reduction of the sensitive functional groups.

Alternative Products

Product Details of 4-Aminobenzonitrile

CAS No. :873-74-5
Formula : C7H6N2
M.W : 118.14
SMILES Code : N#CC1=CC=C(N)C=C1
MDL No. :MFCD00007821
InChI Key :YBAZINRZQSAIAY-UHFFFAOYSA-N
Pubchem ID :13396

Safety of 4-Aminobenzonitrile

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Application In Synthesis of 4-Aminobenzonitrile

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 873-74-5 ]
  • Downstream synthetic route of [ 873-74-5 ]

[ 873-74-5 ] Synthesis Path-Upstream   1~3

  • 1
  • [ 873-74-5 ]
  • [ 93-85-6 ]
References: [1] Patent: EP2354136, 2011, A1, .
[2] Patent: US2011/319423, 2011, A1, .
[3] Patent: CN109419802, 2019, A, .
  • 2
  • [ 873-74-5 ]
  • [ 58633-04-8 ]
YieldReaction ConditionsOperation in experiment
87% With 1,2-diphenyl-1,1,2,2-tetrahydroperoxyethane; hydrogen bromide In water; acetonitrile at 20℃; for 2.5 h; General procedure: To a solution of aniline/phenol (1 mmol) in CH3CN (4 mL), HBr and THPDPE (depending on the substrate as shown in Table 7) were added and the solution was stirred at room temperature. After the reaction was completed, Na2SO3 (3M, 1mL) was added to the stirring mixture followed by the addition of H2O (10 mL). The solution was stirred until the desired precipitates appeared. The products were filtered and more purification was carried out using silica- packed column chromatography (Hexane–EtOAc). All of the products were characterized on the basis of their melting points, IR, 1H NMR, and 13C NMR spectral analysis and compared with those reported
74% With bromine In 1,4-dioxane; sodium hydroxide EXAMPLE 25
PREPARATION OF 4-AMINO-3,5-DIBROMOBENZONITRILE STR37
To a stirred solution of 100 mg (0.847 mmoles) of p-aminobenzonitrile in 3.6 mL dioxane chilled in an ice-bath was added sequentially 356 μL (1.78 moles) of 5N sodium hydroxide solution and mg (1.78 mmoles) of bromine.
The ice-water bath was removed and the reaction mixture was stirred further for 1.5 hours.
After this time, 21.8 μL (0.423 mmoles) of bromine was added to drive the reaction to completion and stirring was continued for 10 minutes.
The mixture was partitioned between ethyl acetate and ice-water and the organic phase was separated.
It was washed with brine, dried over anhydrous sodium sulfate, filtered, and evaporated.
Purification by plate layer chromatography using hexane-ethyl acetate (7:3) as the eluant provided 175 mg (74percent) of the entitled product.
NMR(CDCl3) δ5.1 (bs, 2H), 7.66 (s, 2H).
References: [1] RSC Advances, 2016, vol. 6, # 93, p. 90184 - 90187.
[2] Journal fuer Praktische Chemie (Leipzig), 1986, vol. 328, # 4, p. 497 - 514.
[3] Tetrahedron, 2018, vol. 74, # 45, p. 6584 - 6592.
[4] Journal of Organic Chemistry, 1998, vol. 63, # 5, p. 1555 - 1565.
[5] Journal of the American Chemical Society, 1960, vol. 82, p. 3454 - 3456.
[6] Synthesis (Germany), 2013, vol. 45, # 11, p. 1497 - 1504.
[7] Patent: US5455239, 1995, A, .
  • 3
  • [ 873-74-5 ]
  • [ 58633-04-8 ]
YieldReaction ConditionsOperation in experiment
74% With bromine In 1,4-dioxane; sodium hydroxide EXAMPLE 1
Preparation of 4-Amino-3,5-dibromobenzonitrile STR15
To a stirred solution of 100 mg (0.847 mmoles) of p-aminobenzonitrile in 3.6 mL dioxane chilled in an ice-bath was added sequentially 356 μL (1.78 mmoles) of 5 N sodium hydroxide solution and 284 mg (1.78 mmoles) of bromine.
The ice-water bath was removed and the reaction mixture was stirred further for 1.5 hours.
After this time, 21.8 μL (0.423 mmoles) of bromine was added to drive the reaction to completion and stirring was continued for 10 minutes.
The mixture was partitioned between ethyl acetate and ice-water and the organic phase was separated.
It was washed with brine, dried over anhydrous sodium sulfate, filtered, and evaporated.
Purification by plate layer chromatography using hexane-ethyl acetate (7:3) as eluant provided 175 mg (74percent) of the entitled product.
NMR(CDCl3) δ: 5.1 (bs, 2H), 7.66 (s, 2H).
References: [1] Patent: US5192758, 1993, A, .
 

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