- Iron(II)-promoted synthesis of 2-aminothiazoles via C-N bond formation from vinyl azides and potassium thiocyanate
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A simple protocol to prepare the privileged 2-aminothiazoles promoted by ferrous sulfate heptahydrate via C-N bond formation from vinyl azides and commercially available potassium thiocyanate has been developed. A wide range of vinyl azides are tolerated to afford the expected polysubstituted 2-aminothiazoles in reasonably good yields. The use of the non-toxic substrates and catalyst renders the reaction more environmentally friendly than traditional approaches.
- Zhang, Guolin,Chen, Binhui,Guo, Xiao,Guo, Shanshan,Yu, Yongping
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Read Online
- A fluorescence probe based on 6-phenylimidazo[2,1-: B] thiazole and salicylaldehyde for the relay discerning of In3+ and Cr3+
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A new fluorescence probe, (E)-N′-(2-hydroxybenzylidene)-6-phenylimidazo[2,1-b]thiazole-3-carbohydrazide (LB1), based on 6-phenylimidazo[2,1-b]thiazole and salicylaldehyde was designed and synthesized. The chemical structures of LB1 and its intermediate we
- Li, Bing,Shang, Xiaodong,Li, Linlin,Xu, Yuankang,Wang, Hanyu,Yang, Xiaofeng,Pei, Meishan,Zhang, Ruiqing,Zhang, Guangyou
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Read Online
- Synthesis of lathyrane diterpenoid nitrogen-containing heterocyclic derivatives and evaluation of their anti-inflammatory activities
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As our ongoing work on lathyrane diterpenoid derivatization, three series of lathyrane diterpenoid derivatives were designed and synthesized based combination principles, including pyrazole, thiazole and furoxan moieties. Biological evaluation indicated t
- Wang, Wang,Xiong, Liangliang,Li, Yutong,Song, Zhuorui,Sun, Dejuan,Li, Hua,Chen, Lixia
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- Design, Synthesis, and Cytotoxic Activity of New Tubulysin Analogues
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Synthesis of tubulysin analogues, containing an N-methyl substituent on tubuvaline-amide together with the replacement of either the hydrophobic N-terminal N-methyl pipecolic acid (Mep) or at both N- and C- terminal peptides with available heteroaromatic
- Le, Hai Van,Tran, Loc Van,Tran, Anh Tuan,Tran, Thao Thi Phuong,Tran, Sung Van,Tran, Chien Van
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supporting information
p. 187 - 195
(2021/12/03)
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- A one-pot synthesis of 2-aminothiazoles via the coupling of ketones and thiourea using I2/dimethyl sulfoxide as a catalytic oxidative system
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A series of 2-aminothiazoles is prepared in moderate-to-good yields by the direct coupling of ketones and thiourea using I2/dimethyl sulfoxide as a catalytic oxidative system. This method avoids the preparation of lachrymatory and toxic α-haloketones and the use of an acid-binding agent, thus providing a more convenient approach to 2-aminothiazoles compared to the Hantzsch reaction.
- Zhang, Qian,Wu, Jiefei,Pan, Zexi,Zhang, Wen,Zhou, Wei
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- Amino acid conjugates of aminothiazole and aminopyridine as potential anticancer agents: Synthesis, molecular docking and in vitro evaluation
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Purpose: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate this therapeutic failure. The current study demonstrated the synthesis of 2-aminothiazole [S3 (a-d) and S5(a-d)] and 2-aminopyridine [S4(a-d) and S6(a-d)] derivatives that can target multiple cellular networks implicated in cancer development. Methods: Biological assays were performed to investigate the antioxidant and anticancer potential of synthesized compounds. Redox imbalance and oxidative stress are hallmarks of cancer, therefore, synthesized compounds were preliminarily screened for their antioxidant activity using DPPH assay, and further five derivatives S3b, S3c, S4c, S5b, and S6c, with significant antioxidant potential, were selected for investigation of in vitro anticancer potential. The cytotoxic activities were evaluated against the parent (A2780) and cisplatin-resistant (A2780CISR) ovarian cancer cell lines. Further, Molecular docking studies of active compounds were performed to determine binding affinities. Results: Results revealed that S3c, S5b, and S6c displayed promising inhibition in cisplatin-resistant cell lines in comparison to parent cells in terms of both resistance factor (RF) and IC50 values. Moreover, S3c proved to be most active compound in both parent and resistant cell lines with IC50 values 15.57 μM and 11.52 μM respectively. Our docking studies demonstrated that compounds S3c, S5b, and S6c exhibited significant binding affinity with multiple protein targets of the signaling cascade. Conclusion: Anticancer activities of compounds S3c, S5b, and S6c in cisplatin-resistant cell lines suggested that these ligands may contribute as lead compounds for the development of new anticancer drugs.
- Ali, Tahir,Imran, Muhammad,Li, Jing Bo,Li, Shupeng,Nadeem, Humaira,Naz, Shagufta,Sarwar, Sadia,Shah, Fawad Ali,Tan, Zhen
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p. 1459 - 1476
(2021/04/19)
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- Synthesis process of thiazole medical intermediate
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The invention discloses a synthesis process of thiazole medical intermediate.The synthesis process comprises the following steps: step 1, mixing ethyl pyruvate and dichloromethane of which the volume is 2 times that of the ethyl pyruvate at room temperature, adding an obtained mixture into a reactor, starting stirring, and keeping the temperature of a system at about 20 DEG C; step 2, starting to dropwise add a dichloromethane solution of bromine, controlling the temperature to enable the system to be about 20-30 DEG C, sealing the reactor, and introducing a strong alkali solution to absorb acid gas HBr; and step 3, after dropwise adding is completed, closing a cold well, performing stirring at normal temperature for about 2 hours until the color of the reaction liquid gradually becomes light yellow to light brown, monitoring that no raw material exists through TLC, and concentrating the obtained reaction liquid. According to the synthesis process of the thiazole medical intermediate, by introducing the defoaming agent n-hexane, generated gas foam can be quickly dissolved out and released from the solvent, and the phenomenon of one-time flushing is avoided; and by introducing the n-hexane solvent, solids can be effectively separated out at low temperature, the impurity content can be controlled to be about 1%, the purification difficulty is greatly reduced, and crystallization is facilitated.
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Paragraph 0013; 0015
(2021/06/09)
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- New BI and TRI-Thiazole copper (II) complexes in the search of new cytotoxic drugs against breast cancer cells
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New thiazolyl derivatives (BT and TT) and their copper (II) complexes [Cu2Cl2(BT)2] (Cu-BT) and [Cu4ClO2(TT)2]PF6?3.5H2O (Cu-TT) were synthesized and characterized by elemental analysis, 1H NMR and 13C NMR, HRMS, X-ray diffraction, IR and UV–Vis spectroscopies. The crystal structure of Cu-BT shows the formation of a dinuclear complex where each copper(II) center is bonded to two thiazol N atoms, from different BT ligands, one deprotonated amide N atom, an O atom from the ester terminal groups and a chlorine atom. The structure found for Cu-TT is a positively charged tetranuclear moiety containing two deprotonated TT ligands, a chlorine anion, two hydroxide anions acting as bridges between the copper centers and a water molecule. The cytotoxic activity of both copper complexes was evaluated on metastatic breast cancer cell lines, characterized for its rapidly dividing behavior. Both, Cu-BT and Cu-TT, show higher cytotoxic activity against these tumor cells than free BT and TT and also than cisplatin. In addition, we found that both complexes interact with DNA. Consistently, they also show cytotoxicity against a rapidly dividing non-tumor cell line, although with higher IC50, being such interaction and selectivity an indicator of the possible coexistence of more than one mechanism of action.
- Alvarez, Natalia,Velluti, Francesca,Guidali, Florencia,Serra, Gloria,Gabriela Kramer,Ellena, Javier,Facchin, Gianella,Scarone, Laura,Torre, María H.
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- ω-Quinazolinonylalkyl aryl ureas as reversible inhibitors of monoacylglycerol lipase
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The serine hydrolase monoacylglycerol lipase (MAGL) is involved in a plethora of pathological conditions, in particular pain and inflammation, various types of cancer, metabolic, neurological and cardiovascular disorders, and is therefore a promising target for drug development. Although a large number of irreversible-acting MAGL inhibitors have been discovered over the past years, there are only few compounds known so far which inhibit the enzyme in a reversible manner. Therefore, much effort is put into the development of novel chemical entities showing reversible inhibitory behavior, which is thought to cause less undesired side effects. To explore a wide range of chemical structures as MAGL binders, we have applied a virtual screening approach by docking small molecules into the crystal structure of human MAGL (hMAGL) and envisaged a library of 45 selected compounds which were then synthesized. Biochemical investigations included the determination of the inhibitory potency on hMAGL and two related hydrolases, i.e. human fatty acid amide hydrolase (hFAAH) and murine cholesterol esterase (mCEase). The most promising candidates from theses analyses, i.e. three ω-quinazolinonylalkyl aryl ureas bearing alkyl spacers of three to five methylene groups, exhibited IC50 values of 20–41 μM and reversible, detergent-insensitive behavior towards hMAGL. Among these compounds, the inhibitor 1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-(4-oxo-3,4-dihydroquinazolin-2-yl)butyl)urea (96) was selected for further kinetic characterization, yielding a dissociation constant Ki = 15.4 μM and a mixed-type inhibition with a pronounced competitive component (α = 8.94). This mode of inhibition was further supported by a docking experiment, which suggested that the inhibitor occupies the substrate binding pocket of hMAGL.
- Dato, Florian M.,Neud?rfl, J?rg-Martin,Gütschow, Michael,Goldfuss, Bernd,Pietsch, Markus
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supporting information
(2019/11/13)
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- Synthesis and biological evaluation of imidazo[2,1-b]thiazole based sulfonyl piperazines as novel carbonic anhydrase ii inhibitors
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A novel series of imidazo[2,1-b]thiazole-sulfonyl piperazine conjugates (9aa-ee) has been synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory potency against four isoforms: The cytosolic isozyme hCA I, II and trans-membrane tumor-
- Alvala, Mallika,Angeli, Andrea,Manasa, Kesari Lakshmi,Mohammed, Arifuddin,Pujitha, Sravya,Sethi, Aaftaab,Supuran, Claudiu T.
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- Target-Directed Azide-Alkyne Cycloaddition for Assembling HIV-1 TAR RNA Binding Ligands
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The highly conserved HIV-1 transactivation response element (TAR) binds to the trans-activator protein Tat and facilitates viral replication in its latent state. The inhibition of Tat–TAR interactions by selectively targeting TAR RNA has been used as a strategy to develop potent antiviral agents. Therefore, HIV-1 TAR RNA represents a paradigmatic system for therapeutic intervention. Herein, we have employed biotin-tagged TAR RNA to assemble its own ligands from a pool of reactive azide and alkyne building blocks. To identify the binding sites and selectivity of the ligands, the in situ cycloaddition has been further performed using control nucleotide (TAR DNA and TAR RNA without bulge) templates. The hit triazole-linked thiazole peptidomimetic products have been isolated from the biotin-tagged target templates using streptavidin beads. The major triazole lead generated by the TAR RNA presumably binds in the bulge region, shows specificity for TAR RNA over TAR DNA, and inhibits Tat–TAR interactions.
- Dash, Jyotirmayee,Dutta, Debasish,Paul, Raj,Paul, Rakesh
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supporting information
p. 12407 - 12411
(2020/06/01)
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- N-heterocycles scaffolds as quorum sensing inhibitors. Design, synthesis, biological and docking studies
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Quorum sensing is a communication system among bacteria to sense the proper time to express their virulence factors. Quorum sensing inhibition is a therapeutic strategy to block bacterial mechanisms of virulence. The aim of this study was to synthesize and evaluate new bioisosteres of N-acyl homoserine lactones as Quorum sensing inhibitors in Chromobacterium violaceum CV026 by quantifying the specific production of violacein. Five series of compounds with different heterocyclic scaffolds were synthesized in good yields: thiazoles, 16a–c, thiazolines 17a–c, benzimidazoles 18a–c, pyridines 19a–c and imidazolines 32a–c. All 15 compounds showed activity as Quorum sensing inhibitors except 16a. Compounds 16b, 17a–c, 18a, 18c, 19c and 32b exhibited activity at concentrations of 10 μM and 100 μM, highlighting the activity of benzimidazole 18a (IC50 = 36.67 μM) and 32b (IC50 = 85.03 μM). Pyridine 19c displayed the best quorum sensing inhibition activity (IC50 = 9.66 μM). Molecular docking simulations were conducted for all test compounds on the Chromobacterium violaceum CviR protein to gain insight into the process of quorum sensing inhibition. The in-silico data reveal that all 15 the compounds have higher affinity for the protein than the native AHL ligand (1). A strong correlation was found between the theoretical and experimental results.
- Fuentes-Gutiérrez, Alfredo,Curiel-Quesada, Everardo,Correa-Basurto, José,Martínez-Mu?oz, Alberto,Reyes-Arellano, Alicia
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- Synthesis and SAR studies of novel 1,2,4-oxadiazole-sulfonamide based compounds as potential anticancer agents for colorectal cancer therapy
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A diverse series of 1,2,4-oxadiazoles based substituted compounds were designed, synthesized and evaluated as anticancer agents targeting carbonic anhydrase IX (CAIX). Initial structure-activity analysis suggested that the thiazole/thiophene-sulfonamide conjugates of 1,2,4-oxadiazoles exhibited potent anticancer activities with low μM potencies. Compound OX12 exhibited antiproliferative activity (IC50 = 11.1 μM) along with appreciable inhibition potential for tumor-associated CAIX (IC50 = 4.23 μM) isoform. Therefore, OX12 was structurally optimized and its SAR oriented derivatives (OX17-27) were synthesized and evaluated. This iteration resulted in compound OX27 with an almost two-fold increase in antiproliferative effect (IC50 = 6.0 μM) comparable to the clinical drug doxorubicin and significantly higher potency against CAIX (IC50 = 0.74 μM). Additionally, OX27 treatment decreases the expression of CAIX, induces apoptosis and ROS production, inhibited colony formation and migration of colon cancer cells. Our studies provide preclinical rational for the further optimization of identified OX27 as a suitable lead for the possible treatment of CRC.
- Abid, Mohammad,Alajmi, Mohamed F.,Garrison, Jered,Hasan, Phool,Hussain, Afzal,Imtaiyaz Hassan, Md,Khan, Parvez,King, Hannah M.,Queen, Aarfa,Rana, Sandeep,Rizvi, M. Moshahid Alam,Shamsi, Farheen,Zahid, Muhammad,Zeya, Bushra
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- Synthesis and biological evaluation of 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones
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A series of novel, substituted 2-chloro-3-[(thiazol-2-yl)amino]-1,4-naphthoquinones have been prepared and shown to exhibit promising concentration-dependent activity against human SH-SY5Y cells, Plasmodium falciparum, Mycobacterium tuberculosis and P. aeruginosa. Substituent effects on observed bioactivity have been explored; the para-fluorophenyl derivative 3d exhibited activity across the range of the bioassays employed, indicating the potential of the 2-chloro-3-[(4-arylthiazol-2-yl)amino]-1,4-naphthoquinone scaffold in the development of novel, broad spectrum therapeutics.
- Olawode, Emmanuel O.,Tandlich, Roman,Prinsloo, Earl,Isaacs, Michelle,Hoppe, Heinrich,Seldon, Ronnett,Warner, Digby F.,Steenkamp, Vanessa,Kaye, Perry T.
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supporting information
p. 1572 - 1575
(2019/05/15)
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- Structural optimization and neurotrophic activity evaluation of neurotrophic gentiside derivatives
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C14 alkyl benzoate ABG001, derived from naturally occurring gentisides, was reported to exhibit neurotrophic activity which is similar to NGF (Nerve Growth Factor). In this research, ABG001 was modified by the strategy of isosteric replacement and conformational restriction with the purpose of improving the bioactivity. The cellular neurotrophic activity of those ABG001 derivatives were evaluated, among which 3-hydroxyquinolin-2-(1H)-one A3 and 4-decylphenol ester B7 displayed much better neurotrophic activity compared with ABG001, which highlights the potential of those novel scaffolds for future neurotrophic agent development.
- Wang, Zhenkang,Ma, Chunhua,Wang, Yujie,Xiao, Qiang,Xu, Chenghui,Li, Yingxia
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supporting information
(2019/10/14)
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- Preparation method of key intermediate of acotiamide hydrochloride
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The invention belongs to the field of pharmaceutical intermediates, and particularly relates to a preparation method of a key intermediate of acotiamide hydrochloride. According to the preparation method, ethyl 2-chloroacetoacetate and thiourea serving as raw materials react in the presence of an acid-binding agent and ethylene glycol. The ethylene glycol has excellent reducing performance, so that the reaction can be promoted, and the yield of the reaction is increased. Boron tribromide is added dropwise after the reaction, so that methyl on thiazole can be removed. Lastly, purification is performed to obtain 2-aminothiazole-4-ethyl formate. The preparation method has the advantages of mild reaction conditions, no harsh reaction conditions such as high pressure and high temperature, easiness in product separation and purification, low energy consumption and high economical efficiency.
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Paragraph 0020-0025
(2018/10/04)
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- Synthesis and biological screening of diethyl [N-(thiazol-2-yl)carbamoyl]methylphosphonates
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A three-step synthesis, involving condensation of bromomethyl aryl ketones with urea to afford 2- aminothiazoles, their chloroacetylation and subsequent solvent-free Arbuzov phosphonation has afforded a series of novel diethyl [N-(thiazol-2-yl)carbamoyl]methylphosphonates 3a-3f in good overall yields; the 4- carboxythiazole analogue 3g was obtained by selective hydrolysis of the corresponding ethyl ester 3f. The phosphonate esters exhibited significant anti-cancer activity (nM - low μM IC50 values) against SH-SY5Y cells and, in one case, 7.6 μM MIC90 anti-TB activity against the virulent M. tuberculosis H37Rv strain; the chloroacetamido precursors all exhibited some antimalarial (PfLDH) activity, three with IC50 values in the range 1.0 - 8.9 μM.
- Olawode, Emmanuel O.,Tandlich, Roman,Prinsloo, Earl,Isaacs, Michelle,Hoppe, Heinrich,Seldon, Ronnett,Warner, Digby F.,Steenkamp, Vanessa,Kaye, Perry T.
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p. 110 - 118
(2018/10/26)
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- Synthesis, antimicrobial evaluation and in silico studies of novel 2,4-disubstituted-1,3-thiazole derivatives
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Background: 2,4-disubstituted-1,3-thiazole derivatives (2a–j), (3a–f) and (4a–f) were synthesized, characterized and screened for their potential as antimicrobial agents. In the preliminary screening against a panel of bacterial strains, nine compounds sh
- Masood, Mir Mohammad,Irfan, Mohammad,Alam, Shadab,Hasan, Phool,Queen, Aarfa,Shahid, Shifa,Zahid, Muhammad,Azam, Amir,Abid, Mohammad
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p. 160 - 173
(2019/01/04)
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- Method for synthesizing pharmaceutical intermediate 2-aminothiazole-4-ethyl formate
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The invention discloses a method for synthesizing a pharmaceutical intermediate 2-aminothiazole-4-ethyl formate, ethyl pyruvate, dichloromethane, concentrated sulfuric acid, bromine, ethyl bromopyruvate, thiourea and ethanol are used as main raw materials, and a main factor affecting the product yield during cyclization reaction is the ratio of the important intermediate ethyl bromopyruvate to thethiourea. According to experimental procedures, the ethanol is selected as a solvent, nanocatalyst Cu2O@HKUST-1 is added, under reflux conditions, a desired product with a higher yield can be obtained by optimizing of the material ratio, the intermediate catalyst used in the method shortens the reaction cycle, a solid carbonate is used to adjust the pH of the reaction liquid, the generation of wastewater is reduced, and economic benefits are increased.
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Paragraph 0010; 0012-0030; 0031
(2018/07/30)
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- N,O π-Conjugated 4-Substituted 1,3-Thiazole BF2 Complexes: Synthesis and Photophysical Properties
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A series of 1,3-thiazole-based organoboron complexes has been designed and synthesized by acylation of 2-amino 4-subsituted 1,3-thiazoles with (4-dimethylamino)benzoyl chloride and the subsequent BF2 complexation reaction. The influence of substituents in position 4 of the thiazole ring on photophysical properties of the complexes has been investigated. Synthesized thiazolo[3,2-c][1,3,5,2]oxadiazaborinines mainly showed intensive fluorescence in solutions. Complex with a 4,5-unsubstituted thiazole unit demonstrated an aggregation induced emission (AIE) effect and a very high fluorescent quantum yield (94%) in the solid state because of the inhibition of π-π/π-n interactions in the molecular packing.
- Potopnyk, Mykhaylo A.,Lytvyn, Roman,Danyliv, Yan,Ceborska, Magdalena,Bezvikonnyi, Oleksandr,Volyniuk, Dmytro,Gra?ulevi?ius, Juozas Vidas
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p. 1095 - 1105
(2018/02/09)
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- Design and synthesis of imidazo[2,1-b]thiazole linked triazole conjugates: Microtubule-destabilizing agents
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A series of imidazo[2,1-b]thiazole linked triazole conjugates were synthesized by using Huisgen 1,3-dipolar cyclo-addition reaction (click chemistry approach) and evaluated for their antiproliferative activity against some human cancer cell lines like, HeLa (cervical), DU-145 (prostate), A549 (lung), MCF-7 (breast) and HepG2 (liver). Among them, Conjugates 4g and 4h demonstrated a significant antiproliferative effect against human lung cancer cells (A549) with IC50values of 0.92 and 0.78 μM respectively. Flow cytometric analysis revealed that these conjugates induced cell cycle arrest in G2/M phase in A549 lung cancer cells. The tubulin polymerization assay and immunofluorescence analysis showed that these conjugates effectively inhibit microtubule assembly in cell free and cell based (A549) experiment respectively. Moreover, the apoptosis inducing properties were evaluated by Hoechst staining, mitochondrial membrane potential and Annexin V-FITC assay. Further, western blot analysis was performed for proapoptotic protein Bax and antiapoptotic protein Bcl-2 and the results demonstrated that there was up regulation of Bax and down regulation of Bcl-2 suggesting that these compounds induced apoptosis in human lung cancer cells, A549.
- Shaik, Siddiq Pasha,Nayak, V. Lakshma,Sultana, Faria,Rao, A.V. Subba,Shaik, Anver Basha,Babu, Korrapati Suresh,Kamal, Ahmed
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- ANTIBACTERIAL THERAPEUTICS AND PROPHYLACTICS
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The present disclosure relates generally to novel molecules, compositions, and formulations for treatment of bacterial infections in general and more specifically to bacterial infections with antibiotic resistant pathogens.
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Paragraph 00345
(2017/02/24)
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- 2-amino-thiazole-4-carboxylic acid ethyl ester preparation method
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The invention discloses a 2-aminothiazole-4-ethyl formate preparation method, which takes 2-azido ethyl acrylate and potassium thiocyanate as raw materials, in an organic solvent, inorganic salt is taken as a catalyst to react for generating 2-aminothiazole-4-ethyl formate; mol ratio of 2-azido ethyl acrylate to potassium thiocyanate to inorganic salt is 1: 2: 0.5; the reaction temperature is 60-80 DEG C, and the reaction time is 11-13 hours. The method for preparing 2-aminothiazole-4-ethyl formate has the characteristics of high yield, low production cost and little environmental pollution.
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Paragraph 0029-0030
(2017/03/14)
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- Solvent-free synthesis of bacillamide analogues as novel cytotoxic and anti-inflammatory agents
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Synthesis of fourteen analogues of bacillamide, a bioactive tryptamide alkaloid of marine origin, has been accomplished through a highly efficient convergent route. The present solvent-free protocol involves the formation of thiazole ring in the initial step followed by amide coupling between substituted ethyl 2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxylates and tryptamine in presence of 2-hydroxy-4,6-dimethylpyrimidine, a solid phase catalyst to yield N-[2-(1H-indol-3-yl)ethyl]-2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxamides as bacillamide analogues having structural variation at position-2 of thiazole ring. Bacillamide and its analogues were evaluated for their cytotoxic activity against three cancer cell lines (HCT-116, MDA-MD-231 and JURKAT cell lines) using colorimetric cell proliferation assay. Compounds 17a and 17b exhibited potent anti-cell proliferation activity with IC50values in the range of ~3.0?μM and ~0.1–0.6?μM, respectively against these cell lines. Preliminary mechanism of action studies indicates that these compounds initiate caspase dependent apoptosis. Also, compounds 16d, 16f, 17a and 17d exhibited excellent anti-inflammatory activity comparable to well-known NSAID indomethacin and better to bacillamide, when evaluated using carrageenan induced rat hind paw oedema method.
- Kumar, Sunil,Aggarwal, Ranjana,Kumar, Virender,Sadana, Rachna,Patel, Bhumi,Kaushik, Pawan,Kaushik, Dhirender
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p. 718 - 726
(2016/08/15)
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- N-(2 - (amine methyl) phenyl) thiazole-4-carboxamide derivatives and its preparation method and application (by machine translation)
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This invention involves a kind of N-(2 - (amine methyl) phenyl) thiazole-4-carboxamide derivatives and its preparation method and application. The N-(2 - (amine methyl) phenyl) thiazole-4-carboxamide derivatives having the general formula I is a compound
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Paragraph 0014-0015; 0040-0041
(2016/11/17)
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- Thiazole-4-formyl-piperazine derivatives and its preparation method and application
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The invention relates to thiazole-4-formyl piperazine derivative and a preparing method and application thereof. The thiazole-4-formyl piperazine derivative is compound of the structure shown in a general formula I. The invention further provides the prep
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Paragraph 0012; 0016-0017; 0038-0040
(2016/10/09)
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- 6,5-BICYCLIC OCTAHYDROPYRROLOPYRIDINE OREXIN RECEPTOR ANTAGONISTS
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The present invention is directed to 6,5-bicyclic octahydropyrrolopyridine compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 66
(2016/07/05)
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- A kind of 3,4-dichloro-thiazole derivatives and process for their preparation and use
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The invention provides 3,4-dichloro isothiazole derivatives, their preparation method and application. The invention relates to a heterocyclic compound containing 3,4-dichloro isothiazol, and the compound is represented by the following chemical structural general formula. The invention discloses the structural general formula of the compound, a synthetic method of the compound and applications of the compound as pesticide, bactericide, anti-plant virus agent, and plant activator, and a technology of mixing the compound with agriculturally acceptable auxiliary agents or synergists for preparing pesticide, bactericide, anti-plant virus agent, and plant activator. The invention further discloses the combined application of the compound and the commercial pesticide, bactericide, anti-plant virus agent, and plant activator in controlling diseases, insect pests, and virus diseases in agriculture, forestry and gardening, and a preparation method of the compound and the commercial pesticide, bactericide, anti-plant virus agent, and plant activator.
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Paragraph 0032-0035; 0089-0090
(2016/10/08)
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- THERAPEUTIC COMPOUNDS
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Compounds of formula (I): or salts thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula (I) an
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Page/Page column 27
(2015/05/05)
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- Ethyl 2-((4-Chlorophenyl)amino)thiazole-4-carboxylate and Derivatives Are Potent Inducers of Oct3/4
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The octamer-binding transcription factor 4 (Oct3/4) is a master gene in the transcriptional regulatory network of pluripotent cells. Repression of Oct3/4 in embryonic stem cells (ESCs) is associated with cell differentiation and loss of pluripotency, wher
- Cheng, Xinlai,Yoshida, Hiroki,Raoofi, Dena,Saleh, Sawsan,Alborzinia, Hamed,Wenke, Frank,G?hring, Axel,Reuter, Stefanie,Mah, Nancy,Fuchs, Heiko,Andrade-Navarro, Miguel A.,Adjaye, James,Gul, Sheraz,Utikal, Jochen,Mrowka, Ralf,W?lfl, Stefan
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p. 5742 - 5750
(2015/08/24)
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- Novel Chalcone-Thiazole Hybrids as Potent Inhibitors of Drug Resistant Staphylococcus aureus
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A series of novel hybrids possessing chalcone and thiazole moieties were synthesized and evaluated for their antibacterial activities. In general this class of hybrids exhibited potency against Staphylococcus aureus, and in particular, compound 27 exhibited potent inhibitory activity with respect to other synthesized hybrids. Furthermore, the hemolytic and toxicity data demonstrated that the compound 27 was nonhemolytic and nontoxic to mammalian cells. The in vivo studies utilizing a S. aureus septicemia model demonstrated that compound 27 was as potent as vancomycin. The results of antibacterial activities underscore the potential of this scaffold that can be utilized for developing a new class of novel antibiotics.
- Sashidhara, Koneni V.,Rao, K. Bhaskara,Kushwaha, Pragati,Modukuri, Ram K.,Singh, Pratiksha,Soni, Isha,Shukla,Chopra, Sidharth,Pasupuleti, Mukesh
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supporting information
p. 809 - 813
(2015/08/11)
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- Synthesis, biological evaluation and molecular docking studies of thiazole-based pyrrolidinones and isoindolinediones as anticonvulsant agents
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A series of new 1-(thiazol-2-yl)pyrrolidin-2-one 5a-m and 2-(thiazol-2-yl)isoindoline-1,3-dione 6a-n derivatives were synthesized and evaluated for anticonvulsant activity. The activity was established in three seizure models: PTZ, picrotoxin and MES. Selected compounds were elected for neurotoxicity by the rotarod test. The most active compound of the series was 1-(4-(naphthalen-2-yl)thiazol-2-yl)pyrrolidin-2-one (5g), showing a PTZ effect dose (ED50) value of 18.4 mg/kg in mice. The median toxic dose (TD50) was 170.2 mg/kg, which provided a protection index (PI = TD50/ED50) of 9.2. A computational study was also carried out, including prediction of pharmacokinetic properties and docking studies. The structural assignments of the newly synthesized compounds were elucidated on the basis of spectroscopic data and single-crystal X-ray crystallography. Graphical Abstract: A series of new thiazole-based pyrrolidinones 5a-m and isoindolinediones 6a-l were synthesized and tested as anticonvulsant. The most active compound was 1-(4-(naphthalen-2-yl)thiazol-2-yl)pyrrolidin-2-one (5g), showing ED50 value 18.4 mg/kg.[Figure not available: see fulltext.]
- Ghabbour, Hazem A.,Kadi, Adnan A.,Eltahir, Kamal E. H.,Angawi, Rihab F.,El-Subbagh, Hussein I.
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p. 3194 - 3211
(2015/08/03)
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- HETEROCYCLIC AMINOBERBAMINE DERIVATIVES, THE PREPARATION PROCESS AND USE THEREOF
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The present invention relates to a novel berbamine derivative of formula I or a pharmaceutically acceptable salt thereof, a process for preparation of the same, a pharmaceutical composition comprising said compound and its use in manufacture of an antitumor medicament.
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Paragraph 0104; 0105
(2013/07/19)
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- Concise synthesis and X-ray crystal structure of N -benzyl-2-(pyrimidin-4'- ylamino)-thiazole-4-carboxamide (Thiazovivin), a small-molecule tool for stem cell research
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Stem cell research is one of the most promising fields of modern biomedical research and regenerative medicine. Limited availability and ethical concerns suggest the renouncement of embryonic stem cells (ESCs), thus raising the need for more efficient pro
- Ries, Oliver,Granitzka, Markus,Stalke, Dietmar,Ducho, Christian
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supporting information
p. 2876 - 2882
(2013/09/02)
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- Tuning and predicting biological affinity: Aryl nitriles as cysteine protease inhibitors
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A series of aryl nitrile-based ligands were prepared to investigate the effect of their electrophilicity on the affinity against the cysteine proteases rhodesain and human cathepsin L. Density functional theory calculations provided relative reactivities of the nitriles, enabling prediction of their biological affinity and cytotoxicity and a clear structure-activity relationship.
- Ehmke, Veronika,Quinsaat, Jose Enrico Q.,Rivera-Fuentes, Pablo,Heindl, Cornelia,Freymond, Céline,Rottmann, Matthias,Brun, Reto,Schirmeister, Tanja,Diederich, Fran?ois
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supporting information; experimental part
p. 5764 - 5768
(2012/08/28)
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- Design, synthesis of some new (2-aminothiazol-4-yl)methylester derivatives as possible antimicrobial and antitubercular agents
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A series of (2-aminothiazol-4-yl)methylester (5a-t) derivatives were synthesized in good yields and characterized by 1H NMR, 13C NMR, mass spectral and elemental analyses. The crystal structure of 5a was evidenced by X-ray diffractio
- Karuvalam, Ranjith P.,Haridas, Karickal R.,Nayak, Susanta K.,Guru Row, Tayur N.,Rajeesh,Rishikesan,Kumari, N. Suchetha
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experimental part
p. 172 - 182
(2012/03/27)
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- Dihydropyrimidine Compounds and Their Uses in Preparation of Medicaments for Treating and Preventing Antiviral Diseases
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The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof, to a process for preparing the compound of formula (I), and to use of the compound of formula (I) or a pharmaceutically acceptable salt or
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Page/Page column 15
(2010/04/30)
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- DIHYDROPYRIMIDINE COMPOUNDS AND THEIR USES IN PREPARATION OF MEDICAMENTS FOR TREATING AND PREVENTING ANTIVIRAL DISEASES
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The present invention relates to a compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof, to a process for preparing the compound of formula (I), and to use of the compound of formula (I) or a pharmaceutically acceptable salt or hydrate thereof as a medicament, in particular as a medicament for the treatment and prevention of type B hepatitis.
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Page/Page column 23
(2009/04/23)
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- Concise total synthesis of the thiazolyl peptide antibiotic GE2270 A
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The potent antibiotic thiazolylpeptide GE2270 A was synthesized starting from N-tert-butyloxycarbonyl protected valine in a longest linear sequence of 20 steps and with an overall yield of 4.8 %. Key strategy was the assembly of the 2,3,6-trisubstituted p
- Delgado, Oscar,Martin Mueller,Bach, Thorsten
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experimental part
p. 2322 - 2339
(2009/04/10)
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- QUINOLONES USEFUL AS INDUCIBLE NITRIC OXIDE SYNTHASE INHIBITORS
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The present invention relates to novel quinolones of Formula I that inhibit inducible NOS synthase together with methods of synthesizing and using the compounds including methods for inhibiting or modulating nitric oxide synthesis and/or lowering nitric oxide levels in a patient by administering the compounds for the treatment of disease.
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Page/Page column 56
(2008/12/06)
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- NOVEL PIPERAZINES, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF
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Disclosed are novel piperazine derivatives that act as agonists of the α7 nAChR. Also disclosed are phannaceutical compositions, methods of treating inflammatory conditions, methods of treating CNS disorders, methods for inhibiting cytokine release from mammalian cells and methods for the preparation of the novel compounds.
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Page/Page column 151-152
(2008/06/13)
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- Substituted hydantoins
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The present invention relates to compounds of the formula which are useful in treating diseases characterized by the hyperactivity of MEK. Accordingly the compounds are useful in the treatment of diseases, such as, cancer, cognative and CNS disorders and inflammatory/autoimmune diseases.
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Page/Page column 27-28
(2008/06/13)
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- EP2 RECEPTOR AGONISTS
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A compound of Formula (I) or a salt, solvate and chemically protected form thereof, wherein: R5 is an optionally substituted C5-20 aryl or C4-20 alkyl group; A is selected from the group consisting of Formulae (Ai), (Aii), (Aiii) D is selected from Formulae (Di), (Dii), (Diii), (Div), (Dv) B is selected from the group consisting of Formulae (Bi), (Bii), (Biii), (Biv) (Bv).
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Page/Page column 109
(2008/06/13)
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- MODULATORS OF ATP-BINDING CASSETTE TRANSPORTERS
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The present invention relates to modulators of ATP-Binding Cassette ("ABC") transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator ("CFTR"), compositions thereof, and methods therewith. The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators (I) or a pharmaceutically acceptable salt thereof, wherein: Ht is a 5-membered heteroaromatic ring containing 1-4 heteroatoms selected from O, S, N or NH, wherein said ring is optionally fused to a 6-membered monocyclic or 10-membered bicyclic carbocyclic or heterocyclic, aromatic or non-aromatic ring, wherein Ht is optionally substituted with w occurrences of -WRw, wherein w is 0-5; ring A is 3-7 membered monocyclic ring having 0-3 heteroatoms selected from O, S, N, or NH, wherein ring A is optionally substituted with q occurrences of QRQ; ring B is optionally fused to 5-6 membered carbocyclic or heterocyclic, aromatic or non-aromatic ring .
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Page/Page column 141-142
(2010/02/13)
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- INHIBITORS OF HCV NS5B POLYMERASE
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The present invention porivdes compounds of Formula I, compositons and methods that are useful for treating viral infections and associated diseases, particularly HCV infections and associated diseases.
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- Vanilloid receptor ligands and their use in treatments
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Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.
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- Combination of MTP inhibitors or apoB-secretion inhibitors with fibrates for use as pharmaceuticals
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The invention relates to the use of fibrates for lowering the liver toxicity of MTP inhibitors as well as pharmaceutical compositions containing an MTP inhibitor and a fibrate.
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- Heteroarylcarboxylic acid amides, the preparation thereof and their use as pharmaceutical compositions
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A compound of formula wherein: Aa, Ra, X1 to X4, Het, and R5 to R7 are defined as in claim 1, the isomers and the salts thereof, particularly the physiologically acceptable salts thereof, which are valuable inhibitors of the microsomal triglyceride-transfer protein (MTP), medicaments containing these compounds and their use, as well as the preparation thereof.
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- Synthesis of 2,5-dihalothiazole-4-carboxylates
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An efficient synthesis of 2,5-dihalothiazole-4-carboxylates has been described. Halogenation of aminothiazole carboxylate with NBS or NCS and subsequent diazotization with isoamyl nitrite and halogenation with CuBr2, CuCl2 or CH2I2 provided the corresponding diahalothiazole derivatives. The four-step process described is amenable to scale-up and requires no chromatographic purification in all the steps.
- Okonya, John F,Al-Obeidi, Fahad
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p. 7051 - 7053
(2007/10/03)
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- Design, synthesis, and pharmacological evaluation of new farnesyl protein transferase inhibitors
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New CA1A2X peptidomimetics are described as Ras farnesyl transferase inhibitors (FTIs). They include cysteine and methionine as mimetics of the C-terminus sequence of farnesylated proteins. Furthermore, cysteine was replaced by heter
- Houssin, Raymond,Pommery, Jean,Salaün, Marie-Catherine,Deweer, Sophie,Goossens, Jean-Fran?ois,Chavatte, Philippe,Hénichart, Jean-Pierre
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p. 533 - 536
(2007/10/03)
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