107-91-5Relevant articles and documents
Cyanoacetamide-based oxime carbonates: An efficient, simple alternative for the introduction of Fmoc with minimal dipeptide formation
Khattab, Sherine N.,Subirós-Funosas, Ramon,El-Faham, Ayman,Albericio, Fernando
, p. 3056 - 3062 (2012)
Nowadays, most peptides are chemically achieved by using the Fmoc/tBu protection strategy, due to its fully orthogonal character, mild temporary group removal and resin cleavage steps. However, its introduction into N-unprotected amino acids is not exempt of synthetic inconveniences, such as dipeptide formation. Lately, novel oxime carbonates were introduced in the arsenal of reagents for the introduction of Fmoc, presenting almost negligible percentage of side-products. Herein, an enforced version of this family of Fmoc-carbonates is presented, containing stable and highly acidic cyanoacetamide-based oximes as leaving group. Such reactive species, affordable in only two steps from simple, readily available starting materials, show unusual ability to obtain the corresponding Fmoc-protected residues in high yield and minimal impact of detrimental side-products, mainly Fmoc-dipeptides.
Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity
Ali, Ghada M.E.,Ibrahim, Diaa A.,Elmetwali, Amira M.,Ismail, Nasser S.M.
, p. 1 - 14 (2019)
Different series of novel pyrazole and pyrazolo[1,5-a] pyrimidine derivatives (2a-g), (3a-c), (7a-d) and (10a-e) were designed, synthesized and evaluated for their ability to inhibit CDK2/cyclin A2 enzyme in vitro. In addition, the cytotoxicity of the newly synthesized compounds was screened against four different human cancer cell lines. The CDK2/cyclin A2 enzyme inhibitory activity revealed that compounds (2d) and (2 g) are among the most active with inhibitory activity values of 60% and 40%, respectively, while compounds (7d) and (10b) exhibited the highest activity among the newly synthesized derivatives against four tumor cell lines (HepG2, MCF-7, A549 and Caco2) with IC50 values 24.24, 14.12, 30.03 and 29.27 μM and 17.12, 10.05, 29.95 and 25.24 μM, respectively. Flow cytometry cell cycle assay was carried for compounds (7d) and (10b) to investigate their apoptotic activity. The obtained results revealed that they induced cell-cycle arrest in the G0-G1phase and reinforced apoptotic DNA fragmentation. Molecular modeling studies have been carried out to gain further understanding the binding mode of the target compounds together with field alignment to define the similar field properties.
Synthesis and cytotoxic activity of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group as the A-ring or B-ring
Wang, Fu-Cheng,Peng, Bin,Cao, Sheng-Li,Li, Hong-Yun,Yuan, Xiao-Li,Zhang, Ting-Ting,Shi, Ruifeng,Li, Zhuqing,Liao, Ji,Wang, Hailong,Li, Jing,Xu, Xingzhi
, (2020)
Many natural or synthetic chalcones have potential anti-tumor activity. Here, we synthesized two series of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group and evaluated for their cytotoxic activity towards cultured human lung cancer A549 and colorectal HCT-116 cells. Among them, compound 8d was the most cytotoxic against HCT-116 cells, with an IC50 value of 2.65 μM. Analyses of the phenotypic changes induced by this compound found a dose-dependent accumulation of HCT-116 cells in sub-G1 phase, indicating that compound 8d might induce apoptosis. Furthermore, we found that 8d triggered mitochondrial membrane potential depolarization, promoted reactive oxygen species formation in HCT-116 cells, and increased the percentage of early and late apoptotic cells. Finally, immunoblotting indicated that 8d increased PARP-1 and caspases 3, 7 and 9 cleavage. These data suggest that compound 8d induces apoptosis via the mitochondrial death pathway.
Rational design and synthesis of new PARP1 inhibitors
Romashov, Leonid V.,Zeifman, Alexey A.,Zakharenko, Alexandra L.,Novikov, Fedor N.,Stroilov, Viktor S.,Stroganov, Oleg V.,Chilov, Germes G.,Khodyreva, Svetlana N.,Lavrik, Olga I.,Titov, Ilya Yu.,Svitan'Ko, Igor V.
, p. 15 - 17 (2012)
A preliminary simulation of bioactive compounds followed by their synthesis have been carried out: a set of new fragment PARP1 inhibitors - 3,5,6,7-tetrahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-4-one derivatives - have been obtained. Molecular simulation has shown that binding is characterized by correlated hydrogen bonds with PARP1 and displacement of the highly-conservative water molecule by a polar group.
Modulation of Nitrile Hydratase Regioselectivity towards Dinitriles by Tailoring the Substrate Binding Pocket Residues
Cheng, Zhongyi,Cui, Wenjing,Xia, Yuanyuan,Peplowski, Lukasz,Kobayashi, Michihiko,Zhou, Zhemin
, p. 449 - 458 (2018)
The regioselective hydration of dinitriles is one of the most attractive approaches to prepare ω-cyanocarboxamides or diamides and such regioselectivity is often beyond the capability of chemical catalysts. The use of nitrile hydratase to biotransform dinitriles selectively would be highly desirable. Molecular docking of two aliphatic dinitriles and two aromatic dinitriles into the active site of a nitrile hydratase (NHase) from Rhodococcus rhodochrous J1 allowed the identification of proximal NHase substrate binding pocket residues. Four residues (βLeu48, βPhe51, βTyr68, and βTrp72) were selected for single- and double-point mutations to modulate the NHase regioselectivity towards dinitriles. Several NHase mutants with an altered regioselectivity were obtained, and the best one was Y68T/W72Y. Docking experiments further indicated that the poor binding affinity of aliphatic and aromatic ω-cyanocarboxamides to the NHase variants resulted in distinct regioselectivity between wild-type and mutated NHases.
One-pot sequence for the decarboxylation of α-amino acids
Laval, Gilles,Golding, Bernard T.
, p. 542 - 546 (2003)
Treatment of an α-amino acid with N-bromosuccinimide in water at pH 5 or in an alcoholic-aqueous ammonium chloride mixture, followed by addition of nickel(II) chloride and sodium borohydride, effected an overall decarboxylation via an intermediate nitrile to afford the corresponding amine in good yield.
Synthesis and Docking Study of Novel Pyranocoumarin Derivatives
Karteek, S. Durga,Reddy, A. Gopi,Tej, M. Bhuvan,Rao, M. V. Basaveswara
, p. 272 - 282 (2021/04/02)
Abstract: A new series of fused tricyclic coumarin derivatives were designed, synthesized by a simple and convenient method, starting from 4-hydroxycoumarin and virtually screened by molecular docking on the target protein 3FRZ (PDB ID: 3FRZ), a HCV RNA-dependent RNA polymerase, for potency against hepatitis C virus (HCV). Efficient binding to the target protein was found for most of the synthesized compounds.
Synthesis method of cyanoacetamide
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Paragraph 0021-0030, (2021/08/25)
The invention relates to a synthesis method of cyanoacetamide, and belongs to the technical field of organic synthesis. According to the method, a tubular reactor is used as reaction equipment, malonamide is used as a raw material, and cyanoacetamide is generated under the action of triphosgene. The triphosgene with relatively high reaction activity is used, so that the activation energy of the reaction can be reduced, and the forward proceeding of the reaction is promoted; a pipeline reactor is used as reaction equipment, so that the mass and heat transfer effect of a reaction system can be improved, the reaction time and the retention time of a product in the reaction system are further shortened, and the product purity and yield are effectively improved. The atom utilization rate is high, the by-product ammonium chloride can be sold as a product or used for other reactions, and the recovered solvent and the treated rectification base solution can be used for reactions; and only a small amount of activated carbon waste residues are generated, so that the environment-friendly benefit is high.
PROCESS FOR PREPARING CYANOACETATES
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Paragraph 0033; 0035, (2020/10/28)
This invention relates to a process for producing cyanoacetates using asparagine as a precursor to cyanoacetamide, a staring material to form the cyanoacetates.
Synthesis method of cyanoacetamide
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Paragraph 0024; 0060-0087, (2020/11/26)
The embodiment of the invention provides a cyanoacetamide synthesis method, which comprises the following steps: slowly adding liquid ammonia into a methyl cyanoacetate solution in a reaction environment of -10 DEG C to-5 DEG C; and after the reaction is completed, controlling the reaction environment to be within the range of -15 DEG C to-10 DEG C, and separating out cyanoacetamide crude crystals. Methyl cyanoacetate directly reacts with liquid ammonia, the liquid ammonia gasification step is reduced, and the reaction temperature is reduced. The reaction process is simple, and high reaction yield can be stably obtained.
