24484-93-3Relevant academic research and scientific papers
Sequence selective dual-emission detection of (i, i + 1) bis-phosphorylated peptide using diazastilbene-type Zn(ii)-Dpa chemosensor
Ishida, Yoshiyuki,Inoue, Masa-Aki,Inoue, Tomonori,Ojida, Akio,Hamachi, Itaru
, p. 2848 - 2850 (2009)
This paper describes a new fluorescent chemosensor for phosphorylated peptide, which comprises a rigid trans-4,4′-diazastilbene and two Zn(ii)-Dpa (2,2′-dipicolylamine) units; this chemosensor sequence-selectively binds to a (i, i + 1) bis-phosphorylated peptide and displays a dual-emission fluorescence change.
Design and synthesis of novel 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4- triazol-3-yl)pyridines as potential antitumor agents
Qin, Mingze,Zhai, Xin,Xie, Hongbo,Ma, Junjie,Lu, Kuan,Wang, Yu,Wang, Lihui,Gu, Yucheng,Gong, Ping
, p. 47 - 58 (2014)
New 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4-triazol-3-yl)pyridine derivatives were synthesized and evaluated for their in vitro cytotoxicity against five cancer cell lines namely MKN-45, H460, HT-29, A549 and U87MG, as well as the normal cell line WI-38. Nearly all the compounds exhibited superior potency to sorafenib with a better selectivity towards the MKN-45, H460 and HT-29 cell lines. In addition, the enzymatic screening result demonstrated that the optimized compounds possessed potent Raf kinase inhibition as well as favorable enzyme selectivity. The most promising compound, 11f, showed high levels of cytotoxicity against MKN-45, H460 and HT-29 cells with IC50 values of 51, 72 and 130 nM, respectively, which are 45.5, 30.4 and 27.8 folds higher than the corresponding IC50 values for sorafenib against these cell lines. Structure-activity relationships revealed that the dimethylaminoethyl group was crucial for high activity.
Deaminative chlorination of aminoheterocycles
Cornella, Josep,Faber, Teresa,Gómez-Palomino, Alejandro,Ghiazza, Clément
, (2021/12/23)
Selective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the selectivity of deaminases in nature, herein we present a simple methodology that enables the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)?NH2 can be converted into C(sp2)?Cl bonds. The method is characterized by its wide functional group tolerance and substrate scope, allowing the modification of >20 different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH2 into Cl in a late-stage fashion enables practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents. [Figure not available: see fulltext.]
DINUCLEATING LIGAND OR DINUCLEAR METAL COMPLEX
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Paragraph 0058-0059, (2021/03/19)
To provide a dinuclear metal complex that can be synthesized simply and easily and has a proper anticancer action.SOLUTION: The present disclosure provides a dinucleating ligand represented by the following formula (I) and a dinuclear metal complex thereof (where each X may be the same or different to represent H, Cl, OMe, or, Me, Y is H, a phenyl group, a substituted carbamoyl group or the like).SELECTED DRAWING: None
VISUAL DETECTION OF PLATINATED DNA LESIONS FROM A CLICKABLE CISPLATIN PROBE USED AS DIAGNOSTIC TOOL OR TO IDENTIFY SYNERGISTIC TREATMENTS
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Page/Page column 23, (2017/07/06)
The present invention relates to a new compound for visualizing DNA-platinum crosslink, and its use as a research tool and in screening method for identifying candidate drug to be used in combination with platinating compounds such as cisplatin, carboplatin, and oxaliplatin. Formulae (I), (II) or (III). The project leading to this application has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No [647973]).
A 4 - chloro - 2 - pyridine carboxylic acid methyl ester preparation method (by machine translation)
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Paragraph 0024; 0025, (2017/10/22)
The invention relates to the technical field of pharmaceutical chemistry, in particular to a zola non-nepal intermediate 4 - chloro - 2 - pyridine carboxylic acid methyl ester preparation method. The present invention is to be avoided in the preparation of 4 - chloro - 2 - pyridine carboxylic acid methyl ester in the process 2 - pyridine carboxylic acid to form an oxidation product-mediated multi-kind of impurities occur, to obtain high-purity of 4 - chloro - 2 - pyridine carboxylic acid methyl ester. The specific method is to 2 - pyridine carboxylic acid and chlorinated aliphatic hydrocarbons or chlorinated aromatic hydrocarbon of the solvent composition in the system of adding a certain amount of water, in a certain temperature range by adding thionyl chloride to carry out chlorination reaction in order to prevent pyridine epoxidation. Therefore the method under the same conditions than in the 2 - pyridine carboxylic acid hydrochloride to chlorinated has obvious advantages, synthesis of 4 - chloro - 2 - pyridine carboxylic acid methyl ester high purity, light color. By the 4 - chloro - 2 - pyridine carboxylic acid methyl ester compound of N - methyl - 4 - chloro - 2 - pyridine carboxamide of melting point can be raised to 55 - 56 °C, help to improve the purity of the zola non-nepal, chlorinated reaction time but not obvious extension. (by machine translation)
Allosteric modulators of 5-hydroxytryptamine 2C receptor (5-HT2CR)
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Page/Page column 34, (2017/01/26)
The disclosure is directed to compounds identified as allosteric modulators of 5-HT 2CR, as well as pharmaceutical compositions and methods using the same. Certain embodiments also include methods of identifying and methods of synthesizing the compounds. Optimization and development of allosteric 5-HT 2CR modulators that bind sites other than the primary ligand binding site generate novel, highly selective, and potent ligands of 5-HT2CR. Such molecules can be used as small molecule probes for the nervous system and as effective therapeutics for a variety of diseases.
The structure of the amine-containing thiourea compound and its preparation method and application
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Paragraph 0067; 0068; 0069, (2017/08/08)
A disclosed thiourea compounds containing an arylamine structure comprises compounds of a general formula I and pharmaceutically acceptable salts. In the general formula I shown in the specification, R1 is selected from H, C1-C8 alkyl, halogens, -CF3, -OCF3, -NO2, -CN, R2O-, -SO2NH2, -NHSO2R3, -NR4R5, -CONR6R7, -COOR8, R9CO- and disubstituted and trisubstituted combinations thereof, R2, R3, R4, R5, R6, R7, R8 and R9 are respectively H or C1-C8 alkyl, L is selected from -NHR10, -NHOR11, -NR12R13, pyrrolidin-1-yl, 4-piperidyl and (4-methyl-1-piperazinyl)methylene, and R10, R11, R12 and R13 are respectively H, C1-C8 alkyl, cycloalkyl or aryl. The compounds have inhibiting effect on multiple tumor cell strains.
Chromatin Regulates Genome Targeting with Cisplatin
Zacharioudakis, Emmanouil,Agarwal, Poonam,Bartoli, Alexandra,Abell, Nathan,Kunalingam, Lavaniya,Bergoglio, Valérie,Xhemalce, Blerta,Miller, Kyle M.,Rodriguez, Rapha?l
supporting information, p. 6483 - 6487 (2017/05/29)
Cisplatin derivatives can form various types of DNA lesions (DNA-Pt) and trigger pleiotropic DNA damage responses. Here, we report a strategy to visualize DNA-Pt with high resolution, taking advantage of a novel azide-containing derivative of cisplatin we named APPA, a cellular pre-extraction protocol and the labeling of DNA-Pt by means of click chemistry in cells. Our investigation revealed that pretreating cells with the histone deacetylase (HDAC) inhibitor SAHA led to detectable clusters of DNA-Pt that colocalized with the ubiquitin ligase RAD18 and the replication protein PCNA. Consistent with activation of translesion synthesis (TLS) under these conditions, SAHA and cisplatin cotreatment promoted focal accumulation of the low-fidelity polymerase Polη that also colocalized with PCNA. Remarkably, these cotreatments synergistically triggered mono-ubiquitination of PCNA and apoptosis in a RAD18-dependent manner. Our data provide evidence for a role of chromatin in regulating genome targeting with cisplatin derivatives and associated cellular responses.
Method for preparing methyl 4-chloropicolinate
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Paragraph 0020; 0021, (2017/01/19)
The invention discloses a method for preparing methyl 4-chloropicolinate. The method comprises the following steps: step 1, in the presence of a catalyst, enabling chlorination between a methyl pyridine-2-carboxylate hydrochloride and 2-picolinic acid hydrochloride mixture and sulfoxide chloride; step 2, after chlorination is finished, enabling reaction between the mixture and methanol to generate methyl 4-chloropicolinate. Methyl 4-chloropicolinate prepared by the method is higher in purity, and the melting point of N-methyl-4-chloropyridine-2-carboxamide synthesized by methyl 4-chloropicolinate prepared by the method can be up to 55 DEG C, and sorafenib prepared by follow-up reactions is changed from faint yellow to white, has the liquid-phase purity of 99.9 percent or above, so that the product quality is remarkably improved.
