- A practical synthesis of 3,4-diethoxybenzthioamide based on Friedel-Crafts reaction with potassium thiocyanate in methanesulfonic acid.
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The synthesis of 3,4-diethoxybenzthioamide, the key intermediate for OPC-6535, is achieved by employing Friedel-Crafts reaction of 1,2-diethoxybenzene with potassium thiocyanate in methanesulfonic acid at ambient temperature.
- Aki, Shinji,Fujioka, Takafumi,Ishigami, Masashi,Minamikawa, Jun-ichi
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- An efficient and convenient route for the synthesis of thiophene-2-carboxamidines as potential inhibitors of nitric oxide synthase (NOS)
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A mild and efficient synthesis of substituted thiophene-2-carboxamidines which are potent inhibitors of nitric oxide synthase (NOS) is reported herein. The key step involves reaction of a BOC-protected imidazolyl thiophene-2-carboxamidine reactive intermediate with various primary amines to form BOC-thiophene-2-carboxamidines which could be readily deprotected using TFA to furnish free carboxamidines. The method is very mild and tolerates diverse substituents including sensitive peptide and amino acid fragments. This new methodology represents a substantial improvement to the literature method owing to its simplicity and hassle-free purification procedures.
- Rashid,Singh, Dharmendra,Sanjayan, Gangadhar J.
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- Aerobic Visible-Light Induced Intermolecular S?N Bond Construction: Synthesis of 1,2,4-Thiadiazoles from Thioamides under Photosensitizer-Free Conditions
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Aerobic visible-light induced intermolecular S?N bond construction has been achieved without the addition of photosensitizer, metal, or base. With this strategy, 1,2,4-thiadiazoles can be obtained from thioamides. Preliminary mechanistic investigation suggested that the excited state of thioamides undergoes a single-electron-transfer (SET) process to afford thioamidyl radicals, which can be further transformed into a 1,2,4-thiadiazole through desulfurization and oxidative cyclization. The reaction has good functional group tolerance and represents a green method for the construction of S?N bonds.
- Wang, Hui,Xie, Shihua,Zhu, Hongjun,Zhuo, Liang
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supporting information
p. 3398 - 3402
(2021/06/25)
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- Mo (CO)6-assisted Pd-supported magnetic graphene oxide-catalyzed carbonylation-cyclization as an efficient way for the synthesis of 4(3H)-quinazolinones
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In this paper, a novel catalyst is introduced based on the immobilization of palladium on modified magnetic graphene oxide nanoparticles. The catalyst is characterized by several methods, including transmission electron microscopy, scanning electron microscopy, X-ray fluorescence, vibrating-sample magnetometer, Fourier transform-infrared and dynamic light scattering (DLS) analysis. The activity of the catalyst was investigated in the synthesis of 4(3H)-quinazolinones via Pd-catalyzed carbonylation-cyclization of N-(2-bromoaryl) benzimidamides by Mo (CO)6. The Mo (CO)6 is used as a carbon monoxide source for performing the reaction under mild conditions. The catalyst showed good reusability, and no change in activity was observed after 10?cycles of recovery.
- Bahadorikhalili, Saeed,Ansari, Samira,Hamedifar, Haleh,Ma'mani, Leila,Babaei, Mohsen,Eqra, Rahim,Mahdavi, Mohammad
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- Iminothioethers as Hydrogen Sulfide Donors: From the Gasotransmitter Release to the Vascular Effects
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The gasotransmitter hydrogen sulfide (H2S) is an important tuner of the cardiovascular homeostasis, and its deficiency is etiologically associated with a number of cardiovascular diseases. Therefore, the research of original moieties able to release H2S represents a timely issue for drug discovery. In this work, we developed a collection of iminothioethers (ITEs), exhibiting H2S-releasing properties and producing vasorelaxing effects on rat aortic rings. Derivatives 4 and 11, selected as representative of slow and fast rate H2S donors, respectively, produced a complete recovery of the basal coronary flow, reverting the AngII-induced effects in isolated rat hearts. In addition, studies on human aortic smooth muscle cells (HASMCs) demonstrated membrane hyperpolarizing effects, well related to the intracellular generation of H2S. Taken together, the results obtained support ITEs 4 and 11 as new pharmacological tools, as well as effective and innovative H2S donors for cardiovascular drug discovery.
- Barresi, Elisabetta,Nesi, Giulia,Citi, Valentina,Piragine, Eugenia,Piano, Ilaria,Taliani, Sabrina,Da Settimo, Federico,Rapposelli, Simona,Testai, Lara,Breschi, Maria Cristina,Gargini, Claudia,Calderone, Vincenzo,Martelli, Alma
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p. 7512 - 7523
(2017/09/23)
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- Design, synthesis and Structure-activity relationship studies of new thiazole-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes
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The free fatty acid receptor 1 (FFA1/GPR40) has attracted interest as a novel target for the treatment of type 2 diabetes. Several series of FFA1 agonists including TAK-875, the most advanced compound terminated in phase III studies due to concerns about liver toxicity, have been hampered by relatively high molecular weight and lipophilicity. Aiming to develop potent FFA1 agonists with low risk of liver toxicity by decreasing the lipophilicity, the middle phenyl of TAK-875 was replaced by 11 polar five-membered heteroaromatics. Subsequently, systematic exploration of SAR and application of molecular modeling, leads to the identification of compound 44, which was an excellent FFA1 agonist with robustly hypoglycemic effect both in normal and type 2 diabetic mice, low risks of hypoglycemia and liver toxicity even at the twice molar dose of TAK-875. Meanwhile, two important findings were noted. First, the methyl group in our thiazole series occupied a small hydrophobic subpocket which had no interactions with TAK-875. Furthermore, the agonistic activity revealed a good correlation with the dihedral angle between thiazole core and the terminal benzene ring. These results promote the understanding of ligand-binding pocket and might help to design more promising FFA1 agonists.
- Li, Zheng,Qiu, Qianqian,Xu, Xue,Wang, Xuekun,Jiao, Lei,Su, Xin,Pan, Miaobo,Huang, Wenlong,Qian, Hai
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supporting information
p. 246 - 257
(2016/03/08)
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- Domino aryne precursor: Efficient construction of 2,4-disubstituted benzothiazoles
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An aryne precursor with a potential to perform domino aryne chemistry was proposed and synthesized. The reaction of this reagent with benzothioamide derivatives could afford 2,4-disubstituted benzothiazole with sequential incorporation of C-S, C-N, and C-C bonds on the consecutive three positions of the aryne precursor.
- Shi, Jiarong,Qiu, Dachuan,Wang, Juan,Xu, Hai,Li, Yang
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supporting information
p. 5670 - 5673
(2015/05/20)
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- New hits as antagonists of GPR103 identified by HTS
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Preclinical data indicate that GPR103 receptor and its endogenous neuropeptides QRFP26 and QRFP43 are involved in appetite regulation. A high throughput screening (HTS) for small molecule GPR103 antagonists was performed with the clinical goal to target weight management by modulation of appetite. A high hit rate from the HTS and initial low confirmation with respect to functional versus affinity data challenged us to revise the established screening cascade. To secure high quality data while increasing throughput, the binding assay was optimized on quality to run at single concentration. This strategy enabled evaluation of a larger fraction of chemical clusters and singletons delivering 17 new compound classes for GPR103 antagonism. Representative compounds from three clusters are presented. One of the identified clusters was further investigated, and an initial structure-activity relationship study is reported. The most potent compound identified had a pIC50 of 7.9 with an improved ligand lipophilic efficiency.
- Nordqvist, Anneli,Kristensson, Lisbeth,Johansson, Kjell E.,Isaksson Da Silva, Krystle,Fex, Tomas,Tyrchan, Christian,Svensson Henriksson, Anette,Nilsson, Kristina
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supporting information
p. 527 - 532
(2014/06/09)
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- From liquid to solid-state fluorescence: Tricyclic lactones based on 4-hydroxy-1,3-thiazoles
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This work describes the synthesis of a series of tricyclic lactones based on 4-hydroxy-1,3-thiazoles prepared by the classic Hantzsch synthesis. The tricyclic lactones are more rigid than the parent 4-hydroxythiazoles and are featured not only by fluorescence in solution, but also in the solid state. An extension of the chromophoric system was successfully realized by integration of the benzothiazole substructure, thus resulting in bathochromic shifts of absorption and also fluorescence. The new synthesized lactones additionally show interesting properties in solution, whereby the initial blue fluorescence changes dramatically with a variation of the pH value. Georg Thieme Verlag Stuttgart · New York.
- Calderón Ortiz, Lorena K.,Würfel, Hendryk,T?uscher, Eric,Wei, Dieter,Birckner, Eckhard,G?rls, Helmar,Beckert, Rainer
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p. 126 - 134
(2014/01/06)
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- THIAZOLE COMPOUND AND PREPARATION METHOD AND USE THEREOF
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The present invention relates to thiazole compounds of formula I , the method for preparation and use thereof. More specifically, the present invention relates to novel derivatives of natural product largazole, the method for preparing them and their uses
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Paragraph 0055
(2014/04/03)
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- THIAZOLE COMPOUNDS, METHODS FOR PREPARATION AND USE THEREOF
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The present invention relates to thiazole compounds of formula I, the method for preparation and use thereof. More specifically, the present invention relates to novel derivatives of natural product largazole, the method for preparing them and their uses
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Paragraph 0103-0104
(2014/06/11)
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- Influence of alkyl side chain on the crystallinity and trap density of states in thiophene and thiazole semiconducting copolymer based inkjet-printed field-effect transistors
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The influence of alkyl side chains on the crystallinity of semiconducting copolymer films and their sub-bandgap density-of-states (DOS), the latter being closely related to the stability and the device performance of organic field-effect transistors (OFETs), is investigated. Three different poly(hexathiophene-alt-bithiazole) (PHTBTz) based polymer semiconductors, with identical backbones but different side chain positions and lengths, were synthesized. The crystallinity examined by grazing incidence X-ray diffraction (GIXRD) strongly depends on the number, position, and length of each type of alkyl side chain attached to the thiophene and thiazole copolymer backbones. Also, the sub-bandgap trap DOS distributions were extracted by performing multiple-frequency capacitance-voltage (MF-CV) spectroscopy on the field effect devices. The relationship between film crystallinity and trap DOS in the field-effect transistors can be interpreted in terms of the complex interplay between the number, position, and length of each alkyl side chain for efficient π-π stacking. In particular, the number and position of the alkyl side chain attached to the polymer backbone significantly affects the device performance. Poly(tetryloctylhexathiophene-alt-dioctylbithiazole) (PHTBTz-C8) exhibits the best electrical performance among the different semiconductors synthesized, with a relatively low bulk trap density of ~2.0 × 10 20 cm-3 eV-1 as well as reasonable hole mobility of ~0.25 cm2 V-1 s-1. The microstructural analyses of this organic material strongly suggest that the short π-π stacking distance induces strong interaction between adjacent polymer backbones, which in turn results in enhanced electrical properties.
- Lee, Jiyoul,Chung, Jong Won,Jang, Jaeman,Kim, Do Hwan,Park, Jeong-Il,Lee, Eunkyung,Lee, Bang-Lin,Kim, Joo-Young,Jung, Ji Young,Park, Joon Seok,Koo, Bonwon,Jin, Yong Wan,Kim, Dae Hwan
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p. 1927 - 1934
(2013/07/28)
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- Arylthioamides as H2S donors: L-cysteine-activated releasing properties and vascular effects in vitro and in vivo
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A small library of arylthioamides 1-12 was easily synthesized, and their H2S-releasing properties were evaluated both in the absence or in the presence of an organic thiol such as l-cysteine. A number of arylthioamides (1-3 and 7) showed a slow and l-cysteine-dependent H2S-releasing mechanism, similar to that exhibited by the reference slow H2S- releasing agents, such as diallyl disulfide (DADS) and the phosphinodithioate derivative GYY 4137. Compound 1 strongly abolished the noradrenaline-induced vasoconstriction in isolated rat aortic rings and hyperpolarized the membranes of human vascular smooth muscle cells in a concentration-dependent fashion. Finally, a significant reduction of the systolic blood pressure of anesthetized normotensive rats was observed after its oral administration. Altogether these results highlighted the potential of arylthioamides 1-3 and 7 as H 2S-donors for basic studies, and for the rational design/development of promising pharmacotherapeutic agents to treat cardiovascular diseases.
- Martelli, Alma,Testai, Lara,Citi, Valentina,Marino, Alice,Pugliesi, Isabella,Barresi, Elisabetta,Nesi, Giulia,Rapposelli, Simona,Taliani, Sabrina,Da Settimo, Federico,Breschi, Maria C.,Calderone, Vincenzo
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supporting information
p. 904 - 908
(2013/10/22)
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- Single-step microwave-mediated synthesis of oxazoles and thiazoles from 3-oxetanone: A synthetic and computational study
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The direct microwave-mediated condensation between 3-oxetanone and primary amides and thioamides has delivered moderate to good yields of (hydroxymethyl)oxazoles and (hydroxymethyl)thiazoles. The reactions use a sustainable solvent and only require short reaction times. These are highly competitive methods for the construction of two classes of valuable heteroarenes, which bear a useful locus for further elaboration. Electronic structure calculations have shown that the order of events involves chalcogen atom attack at sp3 carbon and alkyl-oxygen cleavage. The critical role of acid catalysis was shown clearly, and the importance of acid strength was demonstrated. The calculated barriers were also fully consistent with the observed order of thioamide and amide reactivity. Spontaneous ring opening involves a modest degree of C-O cleavage, moderating the extent of strain relief. On the acid-catalysed pathway, C-O cleavage is less extensive still, but proton transfer to the nucleofuge is well advanced with the carboxylic acid catalysts, and essentially complete with methanesulfonic acid. Open sesame: The direct microwave-mediated condensation between 3-oxetanone and primary amides and thioamides has delivered moderate to good yields of oxazoles and thiazoles. The reactions use a sustainable solvent, require only short reaction times and represent a highly competitive method for the construction of two classes of valuable heteroarenes. Electronic structure calculations have been used to probe a range of potential reaction mechanisms (see figure). Copyright
- Orr, David,Tolfrey, Alexandra,Percy, Jonathan M.,Frieman, Joanna,Harrison, Zo? A.,Campbell-Crawford, Matthew,Patel, Vipulkumar K.
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supporting information
p. 9655 - 9662
(2013/07/26)
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- Synthesis and characterization of new 4-hydroxy-1,3-thiazoles
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A series of highly substituted 4-hydroxy-1,3-thiazoles was synthesised in two different ways. Whereas their anions display strong fluorescence in the bathochromic part of the visible spectrum, the emission is shifted hypsochromically upon alkylation reactions. This easy switch between the anion and its derivatives makes them suitable for widespread applications. The thiazoles possess prerequisites for the complexation of metals due to the coexistence of aza-heterocycles and of 1,3-diketone substructures. In addition, the hydroxy group allows further functionalisation reactions, as exemplified by the incorporation of an azide or an acetylene into the product, and by the synthesis of a star-shaped derivative. Georg Thieme Verlag Stuttgart.
- Taeuscher, Eric,Weiss, Dieter,Beckert, Rainer,Goerls, Helmar
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experimental part
p. 1603 - 1608
(2010/06/22)
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- Solvent-free synthesis of 3,5-di(hetero)aryl-1,2,4-thiadiazoles by grinding of thioamides under oxidative conditions
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An efficient and facile synthesis of 3,5-di(hetero)aryl-1,2,4-thiadiazoles by oxidative dimerisation of thioamides by grinding with NBS under solvent-free conditions at room temperature has been developed. The efficiency of this reaction was demonstrated by the compatibility with trifluoromethyl, methyl, methoxy, chloro, pyridyl and thienyl groups. This method has notable advantages in terms of short reaction times, high yields and is a more practical alternative to the existing methods to access these compounds.
- Xu, Yali,Chen, Jiuxi,Gao, Wenxia,Jin, Huile,Ding, Jinchang,Wu, Huayue
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experimental part
p. 151 - 153
(2010/08/06)
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- Synthesis of aromatic thioamide from nitrile without handling of gaseous hydrogen sulfide
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A new method for synthesizing aromatic primary thioamides is described. Simple treatment of aromatic nitriles with sodium hydrogen sulfide and magnesium chloride in dimethylformamide (DMF) gave aromatic primary thioamides in yields of 80-99% without handling of hazardous hydrogen sulfide.
- Manaka, Akira,Sato, Masakazu
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p. 761 - 764
(2007/10/03)
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- Methods for minimizing thioamide impurities
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Methods for minimizing the formation of thioamide compounds using decoy agents during reactions, such as thionations of carbonyl compounds containing nitrite groups, are provided.
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Page/Page column 7; 8
(2008/06/13)
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- Design and synthesis of sulfonyl-substituted 4,5-diarylthiazoles as selective cyclooxygenase-2 inhibitors
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A series of novel sulfone substituted 4,5-diarylthiazoles have been synthesized and evaluated for their inhibition of the two isoforms of human cyclooxygenase (COX-1 and COX-2). This series displays exceptionally selective COX-2 inhibition.
- Carter, Jeffery S.,Rogier,Graneto, Matthew J.,Seibert, Karen,Koboldt, Carol M.,Zhang, Yan,Talley, John J.
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p. 1167 - 1170
(2007/10/03)
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