cas 4815-36-5, 2-AMINO-4-PHENYL-THIOPHENE-3-CARBOXYLIC ACID ETHYL ESTER

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Design, Synthesis, and Structure-Activity Relationship of N-Aryl- N′-(thiophen-2-yl)thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy
The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl)urea, which resulted in the identification of SMU-C80 (EC50 = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1β from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells.
Chen, Zhipeng,Zhang, Lina,Yang, Junjie,Zheng, Lu,Hu, Fanjie,Duan, Siqin,Nandakumar, Kutty Selva,Liu, Shuwen,Yin, Hang,Cheng, Kui
supporting information
p. 7371 - 7389
(2021/06/28)

ECTONUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (ENPP1) MODULATORS AND USES THEREOF
Provided herein are small molecule modulators of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.
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(2021/07/02)

Design, molecular docking and biological evaluation of fused thienopyrimidines and quinazoline
The anticancer activity of the condensed pyrimidine and quinazoline moieties are pronounced with a different pathway. Thienopyrimidine is considered as ring equivalent bioisosteres of quinazolines and present in other heterocyclic compounds including thienopyrimidine. The present investigation focused on the synthesis of thienopyrimidine and quinazoline derivatives for their anticancer activity against the human oral squamous carcinoma-3 (HSC-3) cell line. The synthesized compound confirmed for their structural characteristics from spectral analysis and tested for anti-proliferative activity from MTT assay. The electron-withdrawing group in 4-chloro thienopyrimidines and amino ester derivate/facilitate the inhibition of cancer cells. Further probing by docking studies revealed that the compounds exhibit possible interactions with VEGF, FGFR and c-Met proteins, which are known to have a role in the pathogenesis of oral squamous cell carcinoma. Among the derivatives a moderate activity demonstrated by substituted 4-chloro-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]-pyrimidine (4a) and ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1a) derivatives. Lack of chirality and the presence of bulky substituents in few of the compounds were found to be the cause for lower potency.
Kaliraj,Jeyalakshmi,Kathiravan,Madhavan,Devi, Arikketh
p. 537 - 544
(2021/02/27)

BENZOTHIADIAZINE DERIVATIVES AND COMPOSITIONS COMPRISING THE SAME FOR TREATING DISORDERS MEDIATED BY ADENOSINE
Disclosed herein are novel inhibitors of CD73. More specifically, the novel CD73 inhibitors are derived from benzothiadiazine. Further, the present disclosure is related to the use of said benzothiadiazine derivatives in the treatment of diseases and/or d
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(2020/07/15)

Design, Synthesis, and Biological Evaluation of 6-Substituted Thieno[3,2- d]pyrimidine Analogues as Dual Epidermal Growth Factor Receptor Kinase and Microtubule Inhibitors
The clinical evidence for the success of tyrosine kinase inhibitors in combination with microtubule-targeting agents prompted us to design and develop single agents that possess both epidermal growth factor receptor (EGFR) kinase and tubulin polymerization inhibitory properties. A series of 6-aryl/heteroaryl-4-(3′,4′,5′-trimethoxyanilino)thieno[3,2-d]pyrimidine derivatives were discovered as novel dual tubulin polymerization and EGFR kinase inhibitors. The 4-(3′,4′,5′-trimethoxyanilino)-6-(p-tolyl)thieno[3,2-d]pyrimidine derivative 6g was the most potent compound of the series as an antiproliferative agent, with half-maximal inhibitory concentration (IC50) values in the single- or double-digit nanomolar range. Compound 6g bound to tubulin in the colchicine site and inhibited tubulin assembly with an IC50 value of 0.71 μM, and 6g inhibited EGFR activity with an IC50 value of 30 nM. Our data suggested that the excellent in vitro and in vivo profile of 6g may be derived from its dual inhibition of tubulin polymerization and EGFR kinase.
Romagnoli, Romeo,Prencipe, Filippo,Oliva, Paola,Baraldi, Stefania,Baraldi, Pier Giovanni,Schiaffino Ortega, Santiago,Chayah, Mariem,Kimatrai Salvador, Maria,Lopez-Cara, Luisa Carlota,Brancale, Andrea,Ferla, Salvatore,Hamel, Ernest,Ronca, Roberto,Bortolozzi, Roberta,Mariotto, Elena,Mattiuzzo, Elena,Viola, Giampietro
supporting information
p. 1274 - 1290
(2019/01/30)

Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor
We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs that retain robust negative cooperativity, such as 3. Herein, we report the synthesis and functional profiling of analogues of 3, placing specific emphasis on examining secondary and tertiary amino substituents at the 4-position, combined with a range of substituents at the 5/6-positions (e.g. aromatic/aliphatic carbocycles). We identify analogues with diverse pharmacology at the D2R including NAMs with sub-μM affinity (9h) and, surprisingly, low efficacy partial agonists (9d and 9i).
Fyfe, Tim J.,Kellam, Barrie,Mistry, Shailesh N.,Scammells, Peter J.,Lane, J. Robert,Capuano, Ben
p. 474 - 490
(2019/03/07)

3-CYANOTHIOPHENE DERIVATIVES AS INHIBITORS OF THE PD-1/PD-L1 PROTEIN/PROTEIN INTERACTION
The present invention provides novel compounds of formula (I) that are useful as inhibitors of the PD-l/PD-Ll protein/protein interaction. The compounds may be used in the treatment of cancer, infectious diseases and neurodegenerative diseases such as sch
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(2019/01/22)

One-Pot Synthesis of Thieno[3,2- e]pyrrolo[1,2- a]pyrimidine Derivative Scaffold: A Valuable Source of PARP-1 Inhibitors
A new, efficient, and versatile one-pot cascade reaction of diverse Gewald's aminothiophenes, 2-hydroxy-4-oxobut-2-enoic acid, and derivatives of cyanoacetic acid catalyzed by Et3N is presented. It enables direct synthesis of diverse 1-(2-oxoethylidene)-2-oxothieno[3,2-e]pyrrolo[1,2-a]pyrimidine in good to excellent yields. The reaction exhibits a broad substrate scope and also presents an opportunity for further modification of the structure. The method offers a convenient practical alternative to the known procedures. The synthesized thieno[3,2-e]pyrrolo[1,2-a]pyrimidine scaffold is an important structural motif of new poly(ADP-ribose) polymerase (PARP) inhibitors, playing a useful role in multiple pharmacological applications.
Shipilovskikh, Sergei A.,Rubtsov, Aleksandr E.
supporting information
p. 15788 - 15796
(2019/12/25)

Identification of 4-methoxythieno[2,3-d]pyrimidines as FGFR1 inhibitors
Aim. To identify novel FGFR1 inhibitors using virtual screening approach. Methods. We used methods of organic synthesis, molecular docking via the Autodock 4.2.6 program package and in vitro biochemical tests with γ-32P. Results. In vitro experiments showed that 9 of 23 tested compounds possess inhibitory activity against FGFR1 with IC50 values in the range from 0.9 to 5.6 μM. Conclusions. Nine FGFR1 inhibitors were developed. The mode of compounds binding with the ATP-acceptor site was determined using molecular docking methods and the dependence of the compounds’ activity on the substituents R1, R4 and R5 was evaluated.
Balanda, A. O.,Bdzhola, V. G.,Kotey, I. M.,Pletnova, L. V.,Protopopov, M. V.,Prykhod’ko, A. O.,Starosyla, S. A.,Yarmoluk, S. M.
p. 152 - 162
(2020/06/02)

Design, synthesis and biological evaluations of N-Hydroxy thienopyrimidine-2,4-diones as inhibitors of HIV reverse transcriptase-associated RNase H
Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) is the only HIV enzymatic function not targeted by current antiviral drugs. Although various chemotypes have been reported to inhibit HIV RNase H, few have s
Kankanala, Jayakanth,Kirby, Karen A.,Huber, Andrew D.,Casey, Mary C.,Wilson, Daniel J.,Sarafianos, Stefan G.,Wang, Zhengqiang
supporting information
p. 149 - 161
(2017/10/16)

A Thieno[2,3- d]pyrimidine Scaffold Is a Novel Negative Allosteric Modulator of the Dopamine D2 Receptor
Recently, a novel negative allosteric modulator (NAM) of the D2-like dopamine receptors 1 was identified through virtual ligand screening. This ligand comprises a thieno[2,3-d]pyrimidine scaffold that does not feature in known dopaminergic ligands. Herein, we provide pharmacological validation of an allosteric mode of action for 1, revealing that it is a NAM of dopamine efficacy and identify the structural determinants of this allostery. We find that key structural moieties are important for functional affinity and negative cooperativity, while functionalization of the thienopyrimidine at the 5- and 6-positions results in analogues with divergent cooperativity profiles. Successive compound iterations have yielded analogues exhibiting a 10-fold improvement in functional affinity, as well as enhanced negative cooperativity with dopamine affinity and efficacy. Furthermore, our study reveals a fragment-like core that maintains low μM affinity and robust negative cooperativity with markedly improved ligand efficiency.
Fyfe, Tim J.,Zarzycka, Barbara,Lim, Herman D.,Kellam, Barrie,Mistry, Shailesh N.,Katrich, Vsevolod,Scammells, Peter J.,Lane, J. Robert,Capuano, Ben
p. 174 - 206
(2018/05/14)

4-Substituted thieno[2,3-d]pyrimidines as potent antibacterial agents: Rational design, microwave-assisted synthesis, biological evaluation and molecular docking studies
In an attempt to discover a new class of antibacterial agents with improved efficacy and to overcome the drug-resistant problems, some novel 4-substituted thieno[2,3-d]pyrimidines have been synthesized via microwave-assisted methodology and evaluated for their in vitro antibacterial activity against various pathogenic bacterial strains. Compounds 12b and 13c showed the promising inhibitory potencies against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Escherichia coli with MICs ranging from 2 to 10?μg/ml. Compound 13c was also found to be highly potent against methicillin-resistant S. aureus (MRSA) with MIC value of 4?μg/ml. Docking simulation studies have been performed to unravel the mode of action and association study indicate the binding of potent compounds with DHPS enzyme. In silico ADME studies suggest the drug-like characteristics of the potent compounds.
Gill, Rupinder K.,Singh, Harpreet,Raj, Tilak,Sharma, Anuradha,Singh, Gagandeep,Bariwal, Jitender
p. 1115 - 1121
(2017/10/06)

Design and synthesis of novel protein kinase CK2 inhibitors on the base of 4-aminothieno[2,3-d]pyrimidines
An extension of our previous research work has resulted in a number of new ATP-competitive CK2 inhibitors that have been identified among 4-aminothieno[2,3-d]pyrimidine derivatives. The most active compounds obtained in the course of the research are 3-(5-p-tolyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5e (NHTP23, IC50 = 0.01 μM), 3-(5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5g (NHTP25, IC50 = 0.065 μM) and 3-(6-methyl-5-phenyl-thieno[2,3-d]pyrimidin-4-ylamino)-benzoic acid, 5n (NHTP33, IC50 = 0.008 μM). Structure-activity relationships of the tested 4-aminothieno[2,3-d]pyrimidine derivatives have been studied and their binding mode with ATP-acceptor site of CK2 has been proposed. A negative effect of intramolecular hydrogen bonding in the compounds' structure is discussed.
Ostrynska, Olga V.,Balanda, Anatoliy O.,Bdzhola, Volodymyr G.,Golub, Andriy G.,Kotey, Igor M.,Kukharenko, Olexander P.,Gryshchenko, Andrii A.,Briukhovetska, Nadiia V.,Yarmoluk, Sergiy M.
p. 148 - 160
(2016/04/05)

Identification of the first small-molecule inhibitor of the REV7 DNA repair protein interaction
DNA interstrand crosslink (ICL) repair (ICLR) has been implicated in the resistance of cancer cells to ICL-inducing chemotherapeutic agents. Despite the clinical significance of ICL-inducing chemotherapy, few studies have focused on developing small-molec
Actis, Marcelo L.,Ambaye, Nigus D.,Evison, Benjamin J.,Shao, Youming,Vanarotti, Murugendra,Inoue, Akira,McDonald, Ezelle T.,Kikuchi, Sotaro,Heath, Richard,Hara, Kodai,Hashimoto, Hiroshi,Fujii, Naoaki
supporting information
p. 4339 - 4346
(2016/08/23)

Part 1: Synthesis and visible absorption spectra of some new monoazo dyes derived from ethyl 2-amino-4-(4′-substitutedphenyl)thiophenes
Series of monoazo dyes from some ethyl 2-amino-4-(4′- substitutedphenyl) thiophenes were prepared and characterized. The structure of the substances was confirmed by FT-IR, 1H NMR and mass spectroscopic techniques. The relationship among the structure of the dyes, their absorption characteristics and the solvatochromic and halochromic behaviors of the dyes were investigated. Introduction of electron-accepting substituent into the diazo moiety results in large bathochromic shifts in all solvents used. The dyes exhibited positive solvatochromism and their solvatochromic properties were discussed in relation to tautomerism.
Babür, Banu,Ertan, Nermin
p. 319 - 328
(2014/06/09)

THIENO [2, 3-D] PYRIMIDINE DERIVATIVES AND THEIR USE TO TREAT ARRHYTHMIA
The present invention relates to thienopyrimidine compounds which are potassium channel inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also described.
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(2014/08/06)

Ligand-free Pd-catalyzed C-N cross-coupling/cyclization strategy: An unprecedented access to 1-thienyl pyrroloquinoxalines for the new approach towards apoptosis
The link between PDE4 and apoptosis prompted us to design and synthesize for the first time a series of novel 1-thienyl pyrroloquinoxalines as potential PDE4 inhibitors/apoptotic agents. A ligand-free Pd-catalyzed C-N cross-coupling/cyclization strategy h
Kolli, Sunder Kumar,Nakhi, Ali,Archana, Sivakumar,Saridena, Maneesha,Deora, Girdhar Singh,Yellanki, Swapna,Medisetti, Raghavender,Kulkarni, Pushkar,Ramesh Raju,Pal, Manojit
supporting information
p. 270 - 278
(2014/09/29)

Discovery of novel N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides as potent RORγt inhibitors
Novel series of N-(5-(arylcarbonyl)thiazol-2-yl)amides and N-(5-(arylcarbonyl)thiophen-2-yl)amides were discovered as potent retinoic acid receptor-related orphan receptor-gamma-t (RORγt) inhibitors. SAR studies of the RORγt HTS hit 6a led to identification of thiazole ketone amide 8h and thiophene ketone amide 9g with high binding affinity and inhibitory activity of Th17 cell differentiation. Compound 8h showed in vivo efficacy in both mouse experimental autoimmune encephalomyelitis (EAE) and collagen induced arthritis (CIA) models via oral administration.
Wang, Yonghui,Cai, Wei,Zhang, Guifeng,Yang, Ting,Liu, Qian,Cheng, Yaobang,Zhou, Ling,Ma, Yingli,Cheng, Ziqiang,Lu, Sijie,Zhao, Yong-Gang,Zhang, Wei,Xiang, Zhijun,Wang, Shuai,Yang, Liuqing,Wu, Qianqian,Orband-Miller, Lisa A.,Xu, Yan,Zhang, Jing,Gao, Ruina,Huxdorf, Melanie,Xiang, Jia-Ning,Zhong, Zhong,Elliott, John D.,Leung, Stewart,Lin, Xichen
p. 692 - 702
(2014/01/23)

Facile assembly of two 6-membered fused N-heterocyclic rings: A rapid access to novel small molecules via Cu-mediated reaction
A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for facile assembly of two six membered fused N-heterocyclic rings leading to novel small molecules as potential inhibitors of PDE4. The Royal Society of Chemistry.
Adepu, Raju,Sunke, Rajnikanth,Meda, Chandana L. T.,Rambabu,Krishna, G. Rama,Reddy, C. Malla,Deora, Girdhar Singh,Parsa, Kishore V. L.,Pal, Manojit
supporting information
p. 190 - 192
(2013/02/22)

KG-60-piperazine as a new heterogeneous catalyst for gewald three-component reaction
Piperazine supported on amorphous silica (KG-60-piperazine) as a basic catalyst acts in the Gewald three-component reaction of some aldehydes and ketones with malononitrile as well as ethyl cyanoacetate. The catalyst shows general utility with a variety of starting carbonyl compounds. Moreover, the catalyst can be reused for four additional cycles without significant loss of the activity. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
Rezaei-Seresht, Esmail,Tayebee, Reza,Yasemi, Mohammad
p. 1859 - 1864
(2013/05/21)

THIENO [2, 3 -D] PYRIMIDINE DERIVATIVES AND THEIR USE TO TREAT ARRHYTHMIA
The present invention relates to thienopyrimidine compounds which are potassium channel inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also described.
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(2012/10/18)

Mg/La mixed oxide as an efficient heterogeneous basic catalyst for synthesis of 2-aminothiophenes under microwave irradiation
Microwave-assisted synthesis of 2-aminothiophenes via a Gewald reaction using a heterogeneous strong basic Mg/La mixed oxide catalyst is described.
Moeinpour, Farid,Dorostkar, Nadieh,Vafaei, Majid
experimental part
p. 2367 - 2374
(2012/06/18)

Thieno[3,2-c]pyran-4-one based novel small molecules: Their synthesis, crystal structure analysis and in vitro evaluation as potential anticancer agents
Novel thieno[3,2-c]pyran-4-one based small molecules were designed as potential anticancer agents. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of few steps such as Gewald reaction, Sandmeyer type iodination, Sonogashira type coupling followed by iodocyclization and then Pd-mediated various C-C bond forming reactions. The overall strategy involved the construction of thiophene ring followed by the fused pyranone moiety and then functionalization at C-7 position of the resultant thieno[3,2-c]pyran-4-one framework. Some of the compounds synthesized showed selective growth inhibition of cancer cells in vitro among which two compounds for example, 5d and 6c showed IC50 values in the range of 2.0-2.5 μM. The crystal structure analysis of an active compound along with hydrogen bonding patterns and molecular arrangement present within the molecule is described.
Nakhi, Ali,Adepu, Raju,Rambabu,Kishore, Ravada,Vanaja,Kalle, Arunasree M.,Pal, Manojit
supporting information; experimental part
p. 4418 - 4427
(2012/09/07)

RETINOID-RELATED ORPHAN RECEPTOR GAMMA MODULATORS, COMPOSITION CONTAINING THEM AND USES THEREOF
Provided are retinoid-related orphan receptor gamma(ROR γ) modulators of formula (I), processes for their preparation, pharmaceutical compositions containing them, and their uses in the treatment of diseases mediated by ROR γ.
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(2012/08/08)

Cesium carbonate as a heterogeneous base catalyst for synthesis of 2-aminothiophenes via Gewald reaction
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Moeinpour, Farid,Omidinia, Raheleh,Dorostkar-Ahmadi, Nadieh,Khoshdeli, Bentalhoda
experimental part
p. 2091 - 2092
(2012/02/01)

Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin- 4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2
A novel series of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids has been synthesized and tested in vitro towards human protein kinase CK2. It was revealed that the most active compounds inhibiting CK2 are 3-{[5-(4-methylphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid and 3-{[5-(4-ethoxyphenyl)thieno[2,3-d]pyrimidin-4-yl]thio}propanoic acid (IC 50 values are 0.1 μM and 0.125 μM, respectively). Structure-activity relationships of 28 tested thienopyrimidine derivatives have been studied and binding mode of this chemical class has been predicted. Evaluation of the inhibitors on seven protein kinases revealed considerable selectivity towards CK2.
Golub, Andriy G.,Bdzhola, Volodymyr G.,Briukhovetska, Nadiia V.,Balanda, Anatoliy O.,Kukharenko, Olexander P.,Kotey, Igor M.,Ostrynska, Olga V.,Yarmoluk, Sergiy M.
experimental part
p. 870 - 876
(2011/04/22)

Synthesis and anti-tumor activities of N′-benzylidene-2-(4- oxothieno[2,3-d]pyrimidin-3(4H)-yl)acetohydrazone derivatives
A compound with a cyclic thienopyrimidine moiety and an aceto-hydrazone moiety in its chemical structure was discovered in a cell-based screening to have noticeable cytotoxicity on several tumor cell lines. A total of 38 derivatives of this compound were
Lou, Jiangping,Liu, Zhen,Li, Yan,Zhou, Mi,Zhang, Zhengxi,Zheng, Shu,Wang, Renxiao,Li, Jian
supporting information; experimental part
p. 6662 - 6666
(2011/12/04)

Effects of conformational restriction of 2-amino-3-benzoylthiophenes on A1 adenosine receptor modulation
2-Amino-3-benzoylthiophenes (2A3BTs) have been widely reported to act as allosteric enhancers (AEs) at the A1 adenosine receptor (A 1AR). Herein we describe the synthesis of a series of 1-aminoindeno[1,2-c]thiophen-8-ones and a series of (2-aminoindeno[2,1-b] thiophen-3-yl)(phenyl)methanones as conformationally rigid analogues of the 2A3BTs. These compounds were screened using a functional assay of A 1AR-mediated phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in intact Chinese hamster ovary (CHO) cells to identify both potential agonistic effects as well as the ability to allosterically modulate the activity of the orthosteric agonist, N6-(R- phenylisopropyl)adenosine (R-PIA). All of the 1-aminoindeno[1,2-c]thiophen-8- ones (14a-c and 17a-f) proved either to be inactive or behaved as antagonists in the functional assay. However, the (2-aminoindeno[2,1-b]thiophen-3-yl)(phenyl) methanones with para-chloro substitution (compounds 25b, 25d, and 25f) did significantly augment the R-PIA response, indicating a positive allosteric effect.
Aurelio, Luigi,Valant, Celine,Flynn, Bernard L.,Sexton, Patrick M.,White, Jonathan M.,Christopoulos, Arthur,Scammells, Peter J.
experimental part
p. 6550 - 6559
(2010/11/17)

Synthesis of some novel methyl- and ethyl-2-aminothiophene-3-carboxylate and related Schiff-bases
Methyl- and ethyl-2-amino thiophene-3-carboxylate derivatives 1(a-h) were synthesized by a simple one-pot condensation reaction of the ketone, elemental sulphur and methyl- or ethylcyanoacetate in the presence of morpholine as a catalyst. Further reaction of these compounds with salicylaldehyde gave related Schiff-bases, 2(a-e). Yields of products following recrystallization from ethanol were in the range of 70-85 %. 1H NMR and IR spectra and elemental analysis data were used to identification of these compounds.
Mobinikhaledi,Kalhor,Taheri
experimental part
p. 7399 - 7404
(2012/07/17)

Novel thiophene derivatives as PTP1B inhibitors with selectivity and cellular activity
A series of novel thiophene derivatives was designed, synthesized and their activities as competitive inhibitors of protein tyrosine phosphatase (PTPs) 1B (PTP1B) inhibitors were evaluated. All the compounds showed inhibitory potencies, and 10 of these exhibited moderate inhibitory activities with IC50 values less than 10 μM. The activity of the most potent compound P28 (IC50 = 2.1 μM) was 15 times higher than that of the hit compound P01. Further, four representative compounds (P19, P22, P28, and P31) demonstrated remarkably high selectivities against other PTPs (e.g., PTPα, LAR, CD45, and TCPTP); P19 exhibited greater than sixfold selectivity over highly homologous TCPTP. More importantly, these compounds are permeable to cell membranes. The treatment of CHO-K1 cells with P28 (10 μM) resulted in increased phosphorylation of AKT, which suggested extensive cellular activity of this compound. The novel chemical entities reported in this study could be used for overcoming the poor selectivity and low cellular activity of PTP1B inhibitors and might represent a starting point for development of therapeutic PTP inhibitors.
Ye, Deju,Zhang, Yu,Wang, Fei,Zheng, Mingfang,Zhang, Xu,Luo, Xiaomin,Shen, Xu,Jiang, Hualiang,Liu, Hong
scheme or table
p. 1773 - 1782
(2010/05/02)

2-(3,4-dihydro-4-oxothieno[2,3-d]pyrimidin-2-ylthio) acetamides as a new class of falcipain-2 inhibitors. 3. design, synthesis and biological evaluation
The cysteine protease falcipain-2 (FP-2) of Plasmodium falciparum is a principal cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites, making it become an attractive target enzyme for developing anti-malarial drugs.
Zhu, Jin,Chen, Tong,Liu, Jie,Ruoqun, Ma.,Lu, Weiqiang,Huang, Jin,Li, Honglin,Li, Jian,Jiang, Hualiang
experimental part
p. 785 - 797
(2009/05/27)

Efficient synthesis of substituted 2-amino-3-carbethoxythiophenes
A microwave-assisted method for the synthesis of a variety of thiophene o-aminoesters (2a-l) has been developed, starting from an appropriate aldehyde, methyl ketone or acetoacetate ester with ethyl cyanoacetate in the presence of elemental sulfur. Copyright Taylor & Francis Group, LLC.
Kathiravan,Shishoo,Chitre,Mahadik,Jain
p. 4273 - 4279
(2008/03/13)

Microwave accelerated Gewald reaction: synthesis of 2-aminothiophenes
Microwave-promoted synthesis of 2-aminothiophenes by multicomponent reactions of a ketone with an active nitrile and elemental sulfur under KF-alumina catalysis is described.
Sridhar, Madabhushi,Rao, Rayankula Mallikarjuna,Baba, Nanduri H.K.,Kumbhare, Ravindra M.
p. 3171 - 3172
(2007/10/03)

Discovery and SAR development of thienopyridones: A class of small molecule AMPK activators
AMP-activated protein kinase (AMPK) is well established as a sensor and regulator of intracellular and whole-body energy metabolism. A high-throughput screen was performed in order to identify chemotypes that are bound by AMPK. A novel thienopyridone comp
Zhao, Gang,Iyengar, Rajesh R.,Judd, Andrew S.,Cool, Barbara,Chiou, William,Kifle, Lemma,Frevert, Ernst,Sham, Hing,Kym, Philip R.
p. 3254 - 3257
(2008/02/08)

COMPOUNDS
The invention provides compounds of the formula: (I) wherein R1 is aryl, heteroaryl, cycloalkyl or alkyl; R2 is H, alkyl, nitro, CO2R7, CONR5R6 or halo; R3 and R4 are H, NR5R6, NC(O)R7, halo, trifluromethyl, alkyl, CONR5R6, CO2R7, ni
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(2008/06/13)

SUBSTITUED 3,4-DIHYDROTHIENO [2,3-D] PYRMIDINES AS TISSUE TRANSGLUTAMINASE INHIBITORS
The present invention provides novel compounds and methods useful for treating transglutaminase associated disorders such as celiac spru, Alzheimer's disease and Huntington's disease. Certain compounds of the invention are tissue transglutaminase inhibito
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(2010/11/08)

Aryl alkyl ketones in a one-pot Gewald synthesis of 2-aminothiophenes
2-Aminothiophene-3-carboxylates bearing various aryl groups at the 4-position are readily obtained in good to moderate yields by the one-pot Gewald reaction of aryl alkyl ketones with ethyl cyanoacetate and elemental sulfur in the presence of morpholinium acetate and excess morpholine. Georg Thieme Verlag Stuttgart.
Tormyshev, Victor M.,Trukhin, Dmitry V.,Rogozhnikova, Olga Yu.,Mikhalina, Tatiana V.,Troitskaya, Tatiana I.,Flinn, Anthony
p. 2559 - 2564
(2008/09/16)

Structure-activity relationship study of novel tissue transglutaminase inhibitors
Thieno[2,3-d]pyrimidin-4-one acylhydrazide derivatives were discovered as moderately potent inhibitors of TGase 2 (tissue transglutaminase) utilizing a fluorescence-based assay that measured TGase 2 catalyzed incorporation of the dansylated Lys derivative
Duval, Eric,Case, April,Stein, Ross L.,Cuny, Gregory D.
p. 1885 - 1889
(2007/10/03)

SUBSTITUTED AMINOPYRIMIDINES AS NEUROKININ ANTAGONISTS
The invention discloses tachykinin receptor antagonists. The tachykinin family of receptors comprising the neurokinins substance P (SP), neurokinin A, and neurokinin B and related neuropeptides that are widely distributed in the peripheral and central ner
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Page 49-50

(2008/06/13)

THIENOPYRIMIDINE DERIVATIVES AS POTASSIUM CHANNEL INHIBITORS
The present invention provides thienopyrimidine compounds which are potasium channels inhibitors. Pharmaceutical compositions comprising the compounds and their use in the treatment of arrhythmia are also provided.
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Page 29

(2008/06/13)

Pharmaceutically active compounds and methods of use
New fused thiophene compounds are provided and methods of using those compounds for a variety of therapeutic indications. Compounds of the invention are particularly useful for treatment of neuropathic pain.
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(2008/06/13)