- Microwave mediated synthesis of 2-aminooxazoles
-
A microwave mediated synthesis of 2-aminooxazoles at 150 °C was developed, providing products with a variety of functional groups. The reaction takes 5 min and provides product with a simple precipitation at moderate to good yields without the need for recrystallization or flash chromatography.
- Cronin, Adam,Eagon, Scott,Gleason, Cameron,Johnson, Hunter,Kimball, Joshua J.,Klug, Trevan,Lazaro, Horacio,Liyanage, Duminda,Manjunath, Aashrita,O'Brien, Eli,Schioldager, Ryan,Schmid, Connor,Soderberg, Nathan
-
-
- Synthesis of isothiocyanates using DMT/NMM/TsO? as a new desulfurization reagent
-
Thirty-three alkyl and aryl isothiocyanates, as well as isothiocyanate derivatives from esters of coded amino acids and from esters of unnatural amino acids (6-aminocaproic, 4-(aminomethyl)benzoic, and tranexamic acids), were synthesized with satisfactory or very good yields (25–97%). Synthesis was performed in a “one-pot”, two-step procedure, in the presence of organic base (Et3 N, DBU or NMM), and carbon disulfide via dithiocarbamates, with 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO? ) as a desulfurization reagent. For the synthesis of aliphatic and aromatic isothiocyanates, reactions were carried out in a microwave reactor, and selected alkyl isothiocyanates were also synthesized in aqueous medium with high yields (72–96%). Isothiocyanate derivatives of L-and D-amino acid methyl esters were synthesized, under conditions without microwave radiation assistance, with low racemization (er 99 > 1), and their absolute configuration was confirmed by circular dichroism. Isothiocyanate derivatives of natural and unnatural amino acids were evaluated for antibacterial activity on E. coli and S. aureus bacterial strains, where the most active was ITC 9e.
- Janczewski, ?ukasz,Kolesińska, Beata,Kr?giel, Dorota
-
-
- 4-Dimethylaminopyridine-catalyzed synthesis of isothiocyanates from amines and carbon disulfide
-
Isothiocyanates were synthesized by reactions between primary amines and CS2 in the presence of 4-dimethylaminopyridine as a catalyst and tert-butyl hydroperoxide as an oxidant. Various aryl, benzyl, alkyl, and hydroxyl amines were transformed into the corresponding isothiocyanates in 41–82% yields.
- Rong, Hao-Jie,Chen, Tao,Xu, Ze-Gang,Su, Tian-Duo,Shang, Yu,Wang, Yong-Qiang,Yang, Cui-Feng
-
-
- NaOH-promoted one-pot aryl isothiocyanate synthesis under mild benchtop conditions
-
In this work, we have established a green synthesis of aryl isothiocyanates promoted by the low-cost and readily available NaOH from aryl amines and carbon disulfide in a one-pot procedure. The developed protocol features no extra desulfurating reagents and mild benchtop conditions, in which NaOH serves as both the base and the desulfurating reagent to decompose the dithiocarbamate intermediate. Fourteen examples of aryl amines bearing electronic neutral, rich and poor substituents, as well as benzylamine, have proved to be compatible substrates in the developed method to furnish the corresponding isothiocyanates. The reaction has been performed on a gram scale to further demonstrate its synthetic utility. Compared to the reported base-promoted synthesis of aryl isothiocyanates that requires the use of special equipment, such as the ball mill or the microwave reactor, the simplicity in operation and scalability enables this method to efficiently access a variety of aryl isothiocyanates.
- Li, Hang,Liu, Xinyun,Yin, Xiaogang
-
supporting information
p. 839 - 844
(2021/05/27)
-
- Diaryl-substituted thiosemicarbazone: A potent scaffold for the development of New Delhi metallo-β-lactamase-1 inhibitors
-
The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has become an emerging public health threat. Inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. A potent scaffold, diaryl-substituted thiosemicarbazone, was constructed and assayed with metallo-β-lactamases (MβLs). The obtained twenty-six molecules specifically inhibited NDM-1 with IC50 0.038–34.7 μM range (except 1e, 2e, and 3d), and 1c is the most potent inhibitor (IC50 = 0.038 μM). The structure-activity relationship of synthetic thiosemicarbazones revealed that the diaryl-substitutes, specifically 2-pyridine and 2-hydroxylbenzene improved inhibitory activities of the inhibitors. The thiosemicarbazones exhibited synergistic antimycobacterial actions against E. coli-NDM-1, resulted a 2–512-fold reduction in MIC of meropenem, while 1c restored 16–256-, 16-, and 2-fold activity of the antibiotic on clinical isolates ECs, K. pneumonia and P. aeruginosa harboring NDM-1, respectively. Also, mice experiments showed that 1c had a synergistic antibacterial ability with meropenem, reduced the bacterial load clinical isolate EC08 in the spleen and liver. This work provided a highly promising scaffold for the development of NDM-1 inhibitors.
- Li, Jia-Qi,Sun, Le-Yun,Jiang, Zhihui,Chen, Cheng,Gao, Han,Chigan, Jia-Zhu,Ding, Huan-Huan,Yang, Ke-Wu
-
-
- Discovery of quinazoline derivatives as a novel class of potent and in vivo efficacious LSD1 inhibitors by drug repurposing
-
Histone lysine-specific demethylase 1 (LSD1) is an important epigenetic modulator, and is implicated in malignant transformation and tumor pathogenesis in different ways. Therefore, the inhibition of LSD1 provides an attractive therapeutic target for cancer therapy. Based on drug repurposing strategy, we screened our in-house chemical library toward LSD1, and found that the EGFR inhibitor erlotinib, an FDA-approved drug for lung cancer, possessed low potency against LSD1 (IC50 = 35.80 μM). Herein, we report our further medicinal chemistry effort to obtain a highly water-soluble erlotinib analog 5k (>100 mg/mL) with significantly enhanced inhibitory activity against LSD1 (IC50 = 0.69 μM) as well as higher specificity. In MGC-803 cells, 5k suppressed the demethylation of LSD1, indicating its cellular activity against the enzyme. In addition, 5k had a remarkable capacity to inhibit colony formation, suppress migration and induce apoptosis of MGC803 cells. Furthermore, in MGC-803 xenograft mouse model, 5k treatment resulted in significant reduction in tumor size by 81.6% and 96.1% at dosages of 40 and 80 mg/kg/d, respectively. Our findings indicate that erlotinib-based analogs provide a novel structural set of LSD1 inhibitors with potential for further investigation, and may serve as novel candidates for the treatment of LSD1-overexpressing cancers.
- Li, Zhonghua,Li, Zhongrui,Ma, Jinlian,Miao, Jinxin,Qin, Tingting,Yang, Nian,Zhang, Xinhui,Zhang, Zhenqiang,Zhao, Taoqian,Zhao, Xuan
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-
- A more sustainable isothiocyanate synthesis by amine catalyzed sulfurization of isocyanides with elemental sulfur
-
Isothiocyanates (ITCs) are typically prepared using amines and highly toxic reagents such as thiophosgene, its derivatives, or CS2. In this work, an investigation of a multicomponent reaction (MCR) using isocyanides, elemental sulfur and amines revealed that isocyanides can be converted to isothiocyanates using sulfur and catalytic amounts of amine bases, especially DBU (down to 2 mol%). This new catalytic reaction was optimized in terms of sustainability, especially considering benign solvents such as Cyrene or γ-butyrolactone (GBL) under moderate heating (40 °C). Purification by column chromatography was further optimized to generate less waste by maintaining high purity of the product. Thus, E-factors as low as 0.989 were achieved and the versatility of this straightforward procedure was shown by converting 20 different isocyanides under catalytic conditions, while obtaining moderate to high yields (34-95%). This journal is
- Nickisch,Conen,Gabrielsen,Meier
-
p. 3134 - 3142
(2021/01/28)
-
- Method for preparing isothiocyanate by alkali catalysis
-
The invention discloses a method for preparing isothiocyanate by alkali catalysis, which realizes one-step conversion from primary amine to isothiocyanate under the alkali catalysis. The method comprises the following steps: dissolving primary amine in methanol at -20 to 40 DEG C to obtain a primary amine solution, sequentially adding an alkali catalyst, carbon disulfide and an oxidant into the primary amine solution, carrying out stirring reaction, and carrying out reduced pressure distillation; finally, carrying out extraction and column chromatography purification to obtain the product; wherein the molar ratio of the primary amine to the base catalyst to the carbon disulfide to the oxidizing agent is 1: (0.05-0.2) : (2.5-10) : (1.2-4.5), the structural general formula of the primary amine is RNH2, the structural general formula of the isothiocyanate is R-N=C=S, and the R group is alkyl, aryl, benzyl or allyl. Herein, primary amine reacts with carbon disulfide under the action of analkali catalyst and an oxidizing agent to directly generate isothiocyanate, so that sulfur phosgene and excessive alkali are avoided, and the whole reaction atom economy is high, operation is simple.The method is more suitable for preparation of functional organic intermediates and active biomolecules.
- -
-
Paragraph 0046-0051
(2020/11/22)
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- Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents
-
In this paper, a series of thiosemicarbazone derivatives containing different aromatic heterocyclic groups were synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound 5d displayed significant advantages in inhibition effect with an IC50 value of 0.031 μM, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved respectively). Besides, compound 5d showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound 5d could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, 5d could evidently suppress the cell migration and invasion by blocking the EMT (epithelial–mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer.
- Bo-Wang,He, Zhang-Xu,Li, Yi-Han,Liu, Hong-Min,Ma, Li-Ying,Ma, Qin,Tao, Yuan-Yuan,Wang, Hao-Jie,Wu, Hui-Pan,Zhang, Xin-Hui,Zhao, Bing
-
-
- Synthesis of thiocarbamoyl fluorides and isothiocyanates using amines with CF3SO2Cl
-
A practical and efficient method to synthesize thiocarbamyl fluorides and isothiocyanates from amines with trifluoromethanesulfonyl chloride was developed. In the presence of the reducing agent triphenylphosphine and sodium iodide, thiocarbamyl fluorides and isothiocyanates were synthesized from secondary/primary amine in moderate to excellent yields, respectively. A broad scope of substrates and good functional group compatibility were observed.
- Jiang, Lvqi,Yi, Wenbin,Wei, Jingjing,Liang, Shuaishuai
-
p. 12374 - 12381
(2020/11/10)
-
- Synthetic (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives as promising chemotherapy agents on cell lines infected with HTLV-1
-
Synthesis of four compounds belonging to mesoionic class, (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a-d) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC50 values of all compounds in the range of 1.51-7.70 μM in HTLV-1-infected and non-infected cells. Furthermore, it was observed that 5b could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for 5b could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (5a-d) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:5a-d is spontaneous and moderate (Ka ~ 104 M-1) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream.
- Chaves, Otávio Augusto,De Oliveira, Thais Silva,Echevarria, Aurea,Echevarria-Lima, Juliana,Netto-Ferreira, José C.,Paiva, Rojane O.,Sousa-Pereira, Danilo
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-
- Iron-promoted one-pot approach: Synthesis of isothiocyanates
-
We have established a facile and versatile synthesis for the construction of isothiocyanates from their respective amines in the presence of an eco-friendly, inexpensive, easily available Iron catalyst under mild conditions. This reaction provides the target products through the formation of thiocarbamate salt as an intermediate. Both aromatic amines and aliphatic amines provided the respective target products in moderate to high yield under optimized reaction conditions. However, electron withdrawing substituents were difficult to give target product at room temperature, whereas, they obtained final products in good yield at moderate temperature. In addition, mechanistic studies were revealed that the synthetic route involved iron based subsequent reactions of addition and removal of sulfur.
- Pendem, Venkata Bhavanarushi,Nannapaneni, Madhavi
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p. 485 - 490
(2020/02/18)
-
- Design, synthesis, antiproliferative and antibacterial evaluation of quinazolinone derivatives
-
A series of novel quinazolinone derivatives bearing a disulfide bond were designed and synthesized. Their in vitro antiproliferative activities were evaluated using CCK-8 assay against SMMC-7721, Hela, A549 and MCF-7 human cancer cell lines and normal cell lines L929. The preliminary bioassay results demonstrated that all compounds 7a–7h, 8a–8h and 9a–9h exhibited antiproliferation with various degrees, and some compounds showed better effects than positive control 5-fluorouracil against different cancer cell lines. Among these compounds, 8c and 9f showed significant antiproliferative activity against SMMC-7721 cells with IC50 values of 2.88 and 2.56 μM, respectively. In Hela cells, compounds 9c and 9d showed highly effective biological activity with IC50 values of 3.16 and 2.68 μM, respectively. Compounds 7a and 9a exhibited good inhibitory effect against A549 cells with IC50 values of 3.53 and 3.54 μM, respectively. In MCF-7 cells, compounds 7e, 8e and 9e displayed excellent activity with IC50 values of 1.26, 1.12 and 1.85 μM, respectively. Besides, most of the tested compounds showed low cytotoxic effect against the normal cell lines L929. Biological evaluation indicated that all the tested compounds possessed antibacterial activity with certain degrees.
- Wang, Hai-Xin,Liu, Hai-Ying,Li, Wei,Zhang, Shuai,Wu, Zheng,Li, Xin,Li, Cai-Wen,Liu, Yu-Ming,Chen, Bao-Quan
-
p. 203 - 214
(2019/01/04)
-
- Applications of compound with frostbite preventing and treating effect, and its derivatives
-
The invention relates to a compound with a frostbite preventing and treating effect, and its derivatives, and also relates to an application of the compound in the preparation of drugs for increasingheat production of bodies and preventing cold injuries, and an application of the compound in the preparation of drugs for treating metabolic diseases. The compound and its derivatives provide a potential cold injury-resisting drug for improving the cold resistance of the bodies for cold area operation and combat personnel, and can be developed into effective cold injury-resistant drugs.
- -
-
Paragraph 0060; 0061
(2019/08/30)
-
- Method for jointly preparing isothiocyanate and phosphorus, nitrogen and sulfur flame retardants
-
The invention discloses a method for jointly preparing isothiocyanate and phosphorus, nitrogen and sulfur flame retardants. The method comprises the following steps: taking amine and CS2 as raw materials; generating dithiocarbamate by reacting in a solvent under the existence of alkali; reacting with neopentyl glycol phosphoryl chloride, thereby acquiring an isothiocyanate compound (I); acidizingby-product 1,3,2-phosphorus dioxidehexane thiophosphate (II); generating a salt by reacting with melamine in the solvent, thereby acquiring the phosphorus, nitrogen and sulfur flame retardants (III).According to the method provided by the invention, isothiocyanate and phosphorus, nitrogen and sulfur flame retardants can be jointly prepared; operation is simple and convenient; product yield is high; atom is economical; the prepared phosphorus, nitrogen and sulfur flame retardants (III) have an excellent anti-flaming effect.
- -
-
Paragraph 0014; 0017
(2019/05/22)
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- Organophosphine-free copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur
-
A copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur in the absence of organophosphine has been established. This approach represents a simple and efficient one-pot synthesis of isothiocyanates, and features excellent functional group tolerance and the use of a cheap, safe and odorless sulfur source. Moreover, this process could directly provide isothiocyanate analogous bioactive molecules, thiocarbonyl-containing pesticides and facile construction of benzoxazole and benzimidazole frames.
- Feng, Wei,Zhang, Xing-Guo
-
supporting information
p. 1144 - 1147
(2019/01/28)
-
- Isothiocyanate synthesized by three components and preparation method of isothiocyanate
-
The invention discloses isothiocyanate and a preparation method thereof. The method comprises the steps that primary amine, sodium difluorobromoacetate and elemental sulfur are taken as reactants forreaction; the reaction is carried out under the action of a copper catalyst, wherein the copper catalyst is any one of cuprous chloride, copper bromide, cuprous iodide, copper chloride and copper trifluoromethanesulfonate; an alkali is also added, wherein the alkali is any one of sodium bicarbonate, potassium carbonate, cesium carbonate, potassium phosphate, DABCO and sodium tert-butoxide; the whole reaction is carried out in a solvent, wherein the solvent is acetonitrile or dimethyl sulfoxide, the reaction temperature is 80-120 DEG C, and the reaction time is 10-14 hours. The method can directly synthesize the target product, does not need to separate intermediate products and only needs stirring and heating reaction under normal pressure to obtain the target product, and the yield can beup to 87%; a waste solution is fewer during the reaction, and the method protects the environment and ensures the health of an operator; in addition, a series of isothiocyanate derivatives can be prepared, and the method has a stronger substrate universality.
- -
-
Paragraph 0038
(2019/04/26)
-
- Direct, Microwave-Assisted Synthesis of Isothiocyanates
-
A microwave-assisted desulfuration of readily available dithiocarbamates, formed in situ from primary amines, leading to target isothiocyanates has been developed. This efficient protocol provides a rapid, environmentally benign route to aliphatic and aromatic isothiocyanates.
- Janczewski, ?ukasz,Gajda, Anna,Gajda, Tadeusz
-
supporting information
p. 2528 - 2532
(2019/04/03)
-
- Synthesis of thiocarbamoyl fluorides and isothiocyanates using CF3SiMe3 and elemental sulfur or AgSCF3 and KBr with amines
-
Reactions of thiocarbonyl fluoride derived from cheap, readily available, and widely used CF3SiMe3, elemental sulfur, and KF with secondary amines and primary amines at room temperature in THF provided a wide variety of thiocarbamoyl fluorides and isothiocyanates in moderate to excellent yields, respectively. The two reactions show broad substrate scope and good functional group tolerance. Moreover, AgSCF3 reacts with secondary/primary amines under KBr at room temperature, affording quantitative thiocarbamoyl fluorides/isothiocyanates, which feature late-stage application.
- Zhen, Long,Fan, Hui,Wang, Xiaoji,Jiang, Liqin
-
supporting information
p. 2106 - 2110
(2019/03/26)
-
- A thiourea structure unit including shrinking amino aromatic compound and its preparation method and application (by machine translation)
-
The invention relates to the technical field of pharmaceutical chemistry, and in particular relates to a thiourea structure unit including shrinking amino aromatic compound and its preparation method and application. The present invention provides including shrinking amino thiourea structure unit of the aromatic heterocyclic compound with the gastric cancer cells through the inner metal ion chelating form stable complexes, thereby suppressing the MGC803 gastric cancer cell proliferation activity. The results of the embodiment of the display, and the compound 3 - AP compared with, the present invention provides including shrinking amino thiourea structure unit of the aromatic heterocyclic compound to stomach MGC803 has better proliferation inhibitory activity. (by machine translation)
- -
-
Paragraph 0119-0123; 0137-0141
(2019/07/10)
-
- Synthesis methods for isothiocyanate derivative
-
The invention discloses synthesis methods for an isothiocyanate derivative. The first synthesis method includes reacting raw materials, including primary amine, trifluoromethyltrimethylsilane, potassium fluoride and sulfur, with an organic solvent at the room temperature to obtain the isothiocyanate derivative. The synthetic isothiocyanate derivative has the advantages of simple operation, safety,high efficiency, non-toxicity, low raw material price, mild condition, high yield, wide application range of substrates, high compatibility of functional groups and the like. The second synthesis method includes reacting raw materials, including the primary amine, silver trifluoromethane and potassium bromide, with the organic solvent at the room temperature to obtain the isothiocyanate derivative. The isothiocyanate derivative has the advantages of simple operation, safety, high efficiency, easy availability of the raw materials, nearly quantitative yield, wide application range of the substrates, applicability to selective post-modification of drugs or complex compounds, and the like.
- -
-
Paragraph 0033; 0034; 0035; 0036; 0037; 0038; 0039; 0040
(2019/05/22)
-
- Solvent-Free Enantioselective Michael Reactions Catalyzed by a Calixarene-Based Primary Amine Thiourea
-
An upper-rim functionalized calix[4]arene-based thiourea installed onto the (R,R)-1,2-cyclohexanediamine scaffold was synthesized with a view to investigate its catalytic ability in enantioselective Michael additions. The reactions were found to conveniently proceed under solvent-free conditions, observing good to high enantioselectivities. From this preliminary study, the calix[4]arene unit is likely to play a role in affecting the conversion and to a lesser extent to the stereochemical outcome of the reactions through van der Waals contacts and C-H···π interactions with the substrates.
- De Simone, Nicola Alessandro,Meninno, Sara,Talotta, Carmen,Gaeta, Carmine,Neri, Placido,Lattanzi, Alessandra
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p. 10318 - 10325
(2018/07/13)
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- One-pot three-component tandem reaction: Synthesis of aryl/alkyl cyanamides libraries and their further conversion into tetrazole derivatives
-
We have developed methodology for the synthesis of aryl/alkyl cyanamides from amines in one-pot four steps reaction using cheap, readily available and air stable copper source as catalyst under mild reaction conditions. We have also studied the application of cyanamides. In this connection, we could construct aryl tetrazolamine from cyanamides using click reaction.
- Mandapati, Usharani,Mandapati, Pavan,Pinapati, Srinivasarao,Tamminana, Ramana,Rudraraju, Rameshraju
-
supporting information
p. 500 - 510
(2018/02/06)
-
- Thiazolyl-thiadiazines as Beta Site Amyloid Precursor Protein Cleaving Enzyme-1 (BACE-1) Inhibitors and Anti-inflammatory Agents: Multitarget-Directed Ligands for the Efficient Management of Alzheimer's Disease
-
Alzheimer's disease (AD) is associated with multiple neuropathological events including β-site amyloid precursor protein cleaving enzyme-1 (BACE-1) inhibition and neuronal inflammation, ensuing degeneracy, and death to neuronal cells. Targeting such a complex disease via a single target directed treatment was found to be inefficacious. Hence, with an intention to incorporate multiple therapeutic effects within a single molecule, multitarget-directed ligands (MTDLs) have been evolved. Herein, for the first time, we report the discovery of novel thiazolyl-thiadiazines that can serve as MTDLs as evident from the in vitro and in vivo studies. These MTDLs exhibited BACE-1 inhibition down to micromolar range, and results from the in vivo studies demonstrated efficient anti-inflammatory activity with inherent gastrointestinal safety. Moreover, compound 6d unveiled noteworthy antioxidant, antiamyloid, neuroprotective, and antiamnesic properties. Overall, results of the present study manifest the potential outcome of thiazolyl-thiadiazines for AD treatment.
- Sagar, Sneha R.,Singh, Devendra Pratap,Panchal, Nirupa B.,Das, Rajesh D.,Pandya, Dhaivat H.,Sudarsanam, Vasudevan,Nivsarkar, Manish,Vasu, Kamala K.
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p. 1663 - 1679
(2018/05/14)
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- Na2S2O8-mediated efficient synthesis of isothiocyanates from primary amines in water
-
We have developed two green, practical, and efficient procedures, including a one-pot one, to synthesize isothiocyanates from amines and carbon disulfide via desulfurization with sodium persulfate. Water is used as the solvent. Basic conditions are necessary for good chemoselectivity for isothiocyanates. Structurally diverse linear and branched alkyl amines and aryl amines are readily converted to isothiocyanates by the two procedures in satisfactory yields. Halogens, benzylic C-H bonds, methylthio, nitro, ester, alkenyl, electron-rich or -deficient (hetero)aryls, acetylenyl, and even phenolic and alcoholic hydroxyls are well tolerated. The one-pot procedure in water can also be used to realize the preparation of chiral isothiocyanates from chiral amines, and the modification of bioactive structures with free amino groups. In large-scale preparation, simple and practical purification procedures independent of column chromatography are developed.
- Fu, Zhicheng,Yuan, Wenhao,Chen, Ning,Yang, Zhanhui,Xu, Jiaxi
-
supporting information
p. 4484 - 4491
(2018/10/17)
-
- T3P - A Benign Desulfurating Reagent in the Synthesis of Isothiocyanates
-
A number of alkyl, aryl and bifunctional isothiocyanates are obtained in moderate to high yields (41-94%) in a two-step, one-pot reaction of the parent primary amines or their salts with carbon disulfide, followed by reaction of the thus formed dithiocarbamates with T3P (propane phosphonic acid anhydride) as a new and efficient desulfurating agent.
- Janczewski, ?ukasz,Gajda, Anna,Frankowski, Sebastian,Goszczyński, Tomasz M.,Gajda, Tadeusz
-
p. 1141 - 1151
(2017/12/06)
-
- Synthesis and nematicidal activity of piperazinedione derivatives based on the natural product Barettin
-
Nematodes are serious constraints of crop production worldwide. However, the traditional nematicides suffer from the side-effects, including environmental and human toxicity. Herein, more than 70 novel piperazinedione derivatives based on the natural product Barettin were synthesized and evaluated against the root-knot nematode Meloidogyne incognita (M. incognita). While most of synthesized compounds exhibited certain nematicidal activity at high concentration, the best one showed a nematicidal activity of 75% at 2.4 μmol/L.
- Sun, Haiyang,Li, Hui,Wang, Jiayi,Song, Gonghua
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p. 977 - 980
(2017/11/16)
-
- p-Aromatic Isothiocyanates: Synthesis and Anti Plant Pathogen Activity
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In this study, a series of p-aromatic isothiocyanates are prepared by reacting p-aromatic amines with carbon disulphide and further treating with molecular iodine to yield corresponding isothiocyanate derivatives. The structures of newly synthesized compounds are confirmed by IR, NMR, and MS data. Activity of the products against plant pathogenic fungi and bacteria is tested and the structure-activity relationship is approached. p-Nitrophenyl isothiocyanate most efficiently inhibits Rhizoctonia solani and Erwinia carotovora. The order of seven aromatic isothiocyanates antifungicidal activity is following: p-nitrophenyl > p-methoxyphenyl > p-chlorophenyl > p-methylphenyl > p-ethylphenyl > phenyl > p-fluorophenyl. For antibacterial activity, the order was p-nitrophenyl > p-chlorophenyl > p-methylphenyl > p-ethylphenyl > p-fluorophenyl > phenyl > p-methoxyphenyl. The present study indicates that some of the compounds exhibit promising antimicrobial activity and can be used as an alternative to the traditional synthetic fungicides for controlling R. solani and E. carotovora.
- Tang,Niu,Wang,Huo,Li,Luo,Cao
-
p. 1252 - 1257
(2018/08/16)
-
- Dynamic Ureas with Fast and pH-Independent Hydrolytic Kinetics
-
Low cost, high performance hydrolysable polymers are of great importance in biomedical applications and materials industries. While many applications require materials to have a degradation profile insensitive to external pH to achieve consistent release profiles under varying conditions, hydrolysable chemistry techniques developed so far have pH-dependent hydrolytic kinetics. This work reports the design and synthesis of a new type of hydrolysable polymer that has identical hydrolysis kinetics from pH 3 to 11. The unprecedented pH independent hydrolytic kinetics of the aryl ureas were shown to be related to the dynamic bond dissociation controlled hydrolysis mechanism; the resulting hindered poly(aryl urea) can be degraded with a hydrolysis half-life of 10 min in solution. More importantly, these fast degradable hindered aromatic polyureas can be easily prepared by addition polymerization from commercially available monomers and are resistant to hydrolysis in solid form for months under ambient storage conditions. The combined features of good stability in solid state and fast hydrolysis at various pH values is unprecedented in polyurea material, and will have implications for materials design and applications, such as sacrificial coatings and biomaterials.
- Cai, Kaimin,Ying, Hanze,Cheng, Jianjun
-
supporting information
p. 7345 - 7348
(2018/06/11)
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- Aromatic amine substituted - 1, 2, 3, 4 - thiadiazole and triazole derivatives, their preparation and use
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The invention relates to synthesis of a novel arylamine substituted-1,2,3,4-thiatriazole derivative (I) and an application of the derivative as a disease-resistant plant activator. As proved by activity study, the series of compounds has good prevention and control effects on various plant diseases.
- -
-
Paragraph 0067; 0068; 0069
(2017/07/23)
-
- Synthesis and biological evaluation of terminal functionalized thiourea-containing dipeptides as antitumor agents
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A series of antitumor agents based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for antiproliferative activity using a panel of cancer cell lines, and the effects and mechanism of apoptosis induction were determined. These compounds exhibited significant selectivity to different cancer cell lines with IC50 values at micromolar concentrations. In particular, compound I-11 appeared to be the most potent compound, with an IC50 = 4.85 ± 1.44 μM against the NCI-H460 cell line, at least partly, by the induction of apoptosis. Mechanistically, compound I-11 induced the activation of caspase-12 and CHOP, which triggered apoptotic signalling via the ROS-dependent endoplasmic reticulum pathway and arrested the cell cycle at the S phase. Thus, we concluded that dipeptide derivatives containing the thiourea moiety terminally functionalized by electron-withdrawing substituents may be potential antitumor agents for further investigation.
- Huang, Ri-Zhen,Zhang, Bin,Huang, Xiao-Chao,Liang, Gui-Bin,Qin, Jian-Mei,Pan, Ying-Ming,Liao, Zhi-Xin,Wang, Heng-Shan
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p. 8866 - 8878
(2017/02/10)
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- Synthesis and evaluation of frentizole-based indolyl thiourea analogues as MAO/ABAD inhibitors for Alzheimer's disease treatment
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Alzheimer's disease (AD) is a neurodegenerative disorder associated with an excessive accumulation of amyloid-beta peptide (Aβ). Based on the multifactorial nature of AD, preparation of multi-target-directed ligands presents a viable option to address more pathological events at one time. A novel class of asymmetrical disubstituted indolyl thioureas have been designed and synthesized to interact with monoamine oxidase (MAO) and/or amyloid-binding alcohol dehydrogenase (ABAD). The design combines the features of known MAO inhibitors scaffolds (e.g. rasagiline or ladostigil) and a frentizole moiety with potential to interact with ABAD. Evaluation against MAO identified several compounds that inhibited in the low to moderate micromolar range. The most promising compound (19) inhibited human MAO-A and MAO-B with IC50values of 6.34 μM and 0.30 μM, respectively. ABAD activity evaluation did not show any highly potent compound, but the compound series allowed identification of structural features to assist the future development of ABAD inhibitors. Finally, several of the compounds were found to be potent inhibitors of horseradish peroxidase (HRP), preventing the use of the Amplex Red assay to detect hydrogen peroxide produced by MAO, highlighting the need for serious precautions when using an enzyme-coupled assay.
- Hroch, Lukas,Guest, Patrick,Benek, Ondrej,Soukup, Ondrej,Janockova, Jana,Dolezal, Rafael,Kuca, Kamil,Aitken, Laura,Smith, Terry K.,Gunn-Moore, Frank,Zala, Dominykas,Ramsay, Rona R.,Musilek, Kamil
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p. 1143 - 1152
(2017/02/05)
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- Reaction of Thiocarbonyl Fluoride Generated from Difluorocarbene with Amines
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The reaction of thiocarbonyl fluoride, generated from difluorocarbene, with various amines under mild conditions is described. Secondary amines, primary amines, and o-phenylenediamines are converted to thiocarbamoyl fluorides, isothiocyanates, and difluoromethylthiolated heterocycles, respectively. Thiocarbamoyl fluorides were further transformed into trifluoromethylated amines by using a one-pot process. Thiocarbonyl fluoride is generated in situ and is rapidly fully converted in one pot under mild conditions; therefore, no special safety precautions are needed.
- Yu, Jiao,Lin, Jin-Hong,Xiao, Ji-Chang
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supporting information
p. 16669 - 16673
(2017/12/07)
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- Synthesis and antimicrobial activity of some new 1,2,4-trizoles
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A series of 1,2,4-triazole derivatives were synthesized using appropriate synthetic route and structures were confirmed by IR,1H NMR and elemental analysis. All the synthesized compounds (6a-6h and 7a-7h) were evaluated for antimicrobial activity by determining their minimum inhibitory concentrations (MICs) against a panel of Gram-positive, Gram-negative bacteria and fungi. Most of the compounds showed significant antimicrobial activity against Gram-positive bacteria viz. S. aureus, B. subtilis, Gram-negative bacteria viz. E. coli, P. aerugenosa and fungi viz. C. albicans, A. niger. Some of the compounds showed better antibacterial activities against Gram-positive bacteria compared to Gram-negative bacteria. Compounds 7g, 6g, 6a exhibited good MICs against Gram-positive bacteria and 7f showed better MICs against Gram-negative bacteria compared to reference norfloxacin. Compounds 7f and 7d exhibited MICs which is equipotent to the reference drug ketoconazole.
- Jain, Rakesh Kumar,Mishra, Vikash Kumar,Kashaw, Varsha
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p. 1317 - 1322
(2017/05/02)
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- Copper promoted desulfurization towards the synthesis of isothiocyanates
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The cheap, readily available and air stable catalyst was used as the desulfurization agent for the conversion of aniline to isothiocyanates in one pot two step reaction under mild reaction conditions.
- Mandapati, UshaRani,Pinapati, Srinivasarao,Rudraraju, RameshRaju
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p. 125 - 128
(2016/12/26)
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- Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity
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A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative activity, and N-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1,3-thiazol-2-amine (10s) was determined to be the most potent compound. Tubulin polymerization and immunostaining experiments revealed that 10s potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4. Moreover, 10s effectively induced SGC-7901 cell cycle arrest at the G2/M phase in both concentrationand time-dependent manners. The molecular docking results revealed that 10s could bind to the colchicine binding site of tubulin.
- Sun, Maolin,Xu, Qile,Xu, Jingwen,Wu, Yue,Wang, Yueting,Zuo, Daiying,Guan, Qi,Bao, Kai,Wang, Jian,Wu, Yingliang,Zhang, Weige
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- Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase
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A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (hDHODH) inhibitors. Compounds 26 and 31 displayed IC50 values of 1.75 and 1.12 μM, respectively. The structure-activity relationship was summarized. Further binding mode analysis revealed that compound 31 could form a hydrogen bond with Tyr38 and a water-mediated hydrogen bond with Ala55, which may be necessary for maintaining the bioactivities of the compounds in this series. Further structural optimization of the para- or meta-position of the phenyl group at R will lead to the identification of more potent hDHODH inhibitors.
- Zeng, Fanxun,Qi, Tiantian,Li, Chunyan,Li, Tingfang,Li, Honglin,Li, Shiliang,Zhu, Lili,Xu, Xiaoyong
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p. 1297 - 1302
(2017/07/07)
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- A novel one-pot synthesis of isothiocyanates and cyanamides from dithiocarbamate salts using environmentally benign reagent tetrapropylammonium tribromide
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A highly efficient and simple protocol for the synthesis of isothiocyanates and cyanamides from their respective amines in the presence of a mild, efficient, and non-toxic reagent tetrapropylammonium tribromide is described. High environmental acceptability of the reagents, cost effectiveness and high yields are the important attributes of this methodology.
- Kuotsu, Neivotsonuo Bernadette,Jamir, Latonglila,Phucho, Tovishe,Sinha, Upasana Bora
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p. 832 - 841
(2018/01/17)
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- N,N'-bis-substituted aryl thiourea derivatives and synthetic method and application thereof
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The invention discloses N,N'-bis-substituted aryl thiourea derivatives which are a series of compounds simultaneously containing various substituted aromatic ring structures and asymmetric substituted thiourea structures and are all novel structural compounds which are not reported in the literature. The biological activity test analysis of all the target compounds includes determination of DPPH antioxidant activity and antiviral activity. Results indicate that, in general, the designed and synthesized compounds are novel in structures and have the antioxidant activity and the antiviral activity revealed for the first time. In addition, the unknown biological activity is not fully elucidated, and thus the compounds are expected to provide a certain material basis for further research and development of new drugs.
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Paragraph 0080; 0097; 0098
(2017/04/26)
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- A block containing nicotinamide diphenyl thiourea compound and its salt preparation method and use of
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The invention relates to a diphenyl thiourea compound containing niacinamide building blocks and salt of the diphenyl thiourea compound. The chemical structure of the diphenyl thiourea compound is as shown in the description. The diphenyl thiourea compound and the salt, pharmaceutically acceptable, of the diphenyl thiourea compound have inhibiting effects on various tumour cell strains and can serve as effective components for preparing tumour treatment medicine.
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Paragraph 0085; 0086; 0099
(2017/08/02)
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- Design, Synthesis, EPR-Studies and Conformational Bias of Novel Spin-Labeled DCC-Analogues for the Highly Regioselective Labeling of Aliphatic and Aromatic Carboxylic Acids
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Novel types of spin-labeled N,N′-dicyclohexylcarbodiimides (DCC) are reported that bear a 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) residue on one side and different aromatic and aliphatic cyclohexyl analogues on the other side of the diimide core. These readily available novel reagents add efficiently to aliphatic and aromatic carboxylic acids, forming two possible spin-labeled amide derivatives with different radical distances of the resulting amide. The addition of aromatic DCC analogues proceeds with excellent selectivity, giving amides where the carboxylic acid is exclusively connected to the aromatic residue, while little or no selectivity was observed for the aliphatic congeners. The usefulness of these adducts in structural studies was demonstrated by EPR (electron paramagnetic resonance) measurements of biradical adducts of biphenyl-4,4′-dicarboxylic acids. These analyses also reveal high degrees of conformational bias for aromatic DCC derivatives, which further underlines the powerfulness of these novel reagents. This observation was further corroborated by quantum chemical calculations, giving a detailed understanding of the structural dynamics, while detailed information on the solid state structure of all novel reagents was obtained by X-ray structure analyses.
- G?lz, Jan Philipp,NejatyJahromy, Yaser,Bauer, Mirko,Muhammad, Ashraf,Schnakenburg, Gregor,Grimme, Stefan,Schiemann, Olav,Menche, Dirk
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supporting information
p. 9591 - 9598
(2016/07/14)
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- Synthesis of 4-phenylthieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine-5 (4H)-one derivatives and evaluation of their anti-inflammatory activity
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A series of 4-phenylthieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine-5 (4H)-ones (5a-p) with triazole or other heterocyclic substituents (6-11) was synthesized and the compounds were evaluated for their anti-inflammatory activity using the xylene-induced ear-edema test. Pharmacological analyses showed that the compound 4- (4-chlorophenyl)thieno[2, 3-e][1, 2, 4]triazolo[4, 3-a]pyrimidine- 5 (4H)-one (5m) exhibited the greatest anti-inflammatory activity (50.48% inhibition, 30 min after intraperitoneal administration) and was more potent than the reference drug, indomethacin. The peak activity of 5m was observed 4 h after oral administration, and it showed a higher anti-inflammatory activity than indomethacin did at a dose of 100 mg/kg.
- Pan, Fu-Jun,Wang, Shi-Ben,Liu, Da-Chuan,Gong, Guo-Hua,Quan, Zhe-Shan
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p. 141 - 148
(2016/03/12)
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- An efficient methodology for the synthesis of thioureas from amine mediated by a cobalt source
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The cheap, readily available and air stable cobalt catalyst was used as the desulfurization agent for the conversion of aniline to thioureas in one pot three step reaction under mild reaction conditions. The reactions are rapid and facile and accomplished at room temperature.
- Seelam, Mohan,Shaikh, Baji Vali,Tamminana, Ramana,Kammela, Prasada Rao
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supporting information
p. 5297 - 5300
(2016/11/11)
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- Cobalt mediated by desulfurization toward the synthesis of isothiocyanates
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A highly efficient and simple protocol for the construction of aromatic and aliphatic isothiocyanates from their respective amines in the presence of cheap, readily available, and air-stable cobalt catalyst is described. All reactions were carried out under optimized reaction conditions and gave target products in good to excellent yields within shorter reaction time.
- Seelam, Mohan,Shaik, Bajivali,Kammela, Prasada Rao
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supporting information
p. 1759 - 1765
(2016/10/31)
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- Double three bromo 1,3-di-pyridine salt-based propane and its preparation method, method of use, recovery method and application
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The invention discloses a double tribromo 1,3-bipyridine onium salt dimethylmethane, and a preparation method, an application method, a recovery method and application thereof. The preparation method comprises the following steps: dissolving 1,3-bipyridine onium salt dimethylmethane by using water, and then adding potassium bromide; adding potassium peroxymonosulfate sulfate compound brine solution to prepare a clear solution after dissolving potassium bromide, and then stirring and reacting at -10 to 0 DEG C until solid is separated out; separating out solid, so as to obtain the double tribromo 1,3-bipyridine onium salt dimethylmethane. The product can be used for preparing isothiocyanate, aromatic thiourea or acetanilide. The preparation method disclosed by the invention is mild in condition, and simple to operate the reaction process, and raw materials are easily available. The double tribromo 1,3-bipyridine onium salt dimethylmethane not only can be used as a brominating reagent, but also can be used as organic synthesis intermediates, meanwhile, the reaction efficiency is improved, and the double tribromo 1,3-bipyridine onium salt dimethylmethane is convenient to recover and can be recycled.
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Paragraph 0080; 0081; 0085; 0086
(2016/10/07)
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- NOVEL BENZIMIDAZOLE BASED EGFR INHIBITORS
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The present invention disclosed a novel EGFR inhibitor compound of formula (I), process for preparation thereof and methods of treating abnormal cell growth in mammals by administering the compounds of formula (I). Wherein, R= -H, 3-CH3, 4-NO2, 4-Cl, 2-CH3, 4-CH3, 4-Br, 4-F R1= -H, -4-OCH3, -4-NO2,-2-NO2, -4-Cl, -2,4,6-CH3, -4-CH3, -2-F,4-Br, -4-CF3, -4-S-CH3, -4-Cl,-3-CF3, -3-S-CH3, -3,5-CF3, -2-S-CH3, -3-CF3,-4-OCF3, -Si-(CH3)3, -Si-(C2H5)3, (CH3)2-Si- C2H5.
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Page/Page column 12
(2016/06/15)
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- NOVEL FLAVONE BASED EGFR INHIBITORS AND PROCESS FOR PREPARATION THEREOF
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The present invention discloses a novel EGFR inhibitor compound of formula (1), process for preparation thereof and methods of treating abnormal cell growth in mammals by administering the compounds of formula (1). wherein, R is selected from hydrogen, alkyl, nitro, halogens such as chlorine, bromine, fluorine and iodine; Rl= hydrogen, alkyl, alkoxy, aryl, nitro, halogens such as chlorine, bromine, fluorine and iodine, trifluoromethyl, thioalkyl, trifluromethoxy, trialkylsilyl.
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Page/Page column 13
(2016/09/22)
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- Heterocyclic compounds useful for kinase inhibition
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Provided herein are compounds useful for kinase inhibition.
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Page/Page column 93
(2016/04/02)
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- The synthesis of sulforaphane analogues and their protection effect against cisplatin induced cytotoxicity in kidney cells
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A series of sulforaphane analogues were synthesized with various amines by treatment of carbon disulfide followed by Boc2O and DMAP. These synthesized sulforaphane analogues were tested on cisplatin treated cultured LLC-PK1 kidney cell line. Among these analogues, several compounds including SF5 show a potent effect on kidney cell protection assay at the concentration of 2.5 μM. Further studies with compound SF5 revealed that the kidney cell protection effect was related by inhibiting the apoptosis pathway through JNK-p53-caspase apoptotic cascade. Compound SF5 may be considered as a promising candidate for the development of new kidney protection agent against drug induced acute kidney disease.
- Kim, Taejung,Kim, Young-Joo,Han, Im-Ho,Lee, Dahae,Ham, Jungyeob,Kang, Ki Sung,Lee, Jae Wook
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supporting information
p. 62 - 66
(2015/02/19)
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