24237-54-5Relevant academic research and scientific papers
Synthesis, in vitro antimycobacterial evaluation and docking studies of some new 5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one schiff bases
Narender, Malothu,Jaswanth, S. Bhandaru,Umasankar, Kulandaivelu,Malathi, Jojula,Raghuram Reddy, Adidala,Umadevi,Dusthackeer,Venkat Rao, Kaki,Raghuram, R. Akkinepally
, p. 836 - 840 (2016)
Development of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis (TB) has been considered as major health burden, globally. In order to develop novel, potential molecules against drug resistant TB, twenty two (22) new 3-substituted-7-benzyl-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one (6a-k) and 3-substituted-7-benzyl-2-methyl-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-4(3H)-one (7a-k) derivatives were designed and synthesized by using appropriate synthetic protocols. Pantothenate synthetase (PS) was considered as the target for the molecular docking studies and evaluated the binding pattern at active site, as PS plays a significant role in the biosynthesis of pantothenate in Mycobacterium tuberculosis (MTB). The preliminary in vitro antibacterial screening of test compounds was carried out against two strains of Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli and Klebsiella pneumoniae) bacteria. The antimycobacterial screening was performed against MTB H37Rv and an isoniazid-resistant clinical isolate of MTB. The compounds 6b, 6c, 6d, 6k, 7b, 7c, 7d and 7k exhibited promising antibacterial activity MIC in the range of 15-73 μM against all bacterial strains used and compounds 6d and 7b showed antimycobacterial activity (IC50340 μM in LRP assay) and (MIC 9 μM in broth microdilution method).
2-Substituted thienotetrahydropyridine derivatives: Allosteric ectonucleotidase inhibitors
Gütschow, Michael,Keuler, Tim,Lee, Sang-Yong,Müller, Christa E.,Mirza, Salahuddin,Namasivayam, Vigneshwaran,Pelletier, Julie,Pietsch, Markus,Pillaiyar, Thanigaimalai,Sévigny, Jean,Sch?kel, Laura,Sylvester, Katharina
, (2021/11/01)
The antithrombotic prodrugs ticlopidine and clopidogrel are thienotetrahydro-pyridine derivatives that are metabolized in the liver to produce thiols that irreversibly block adenosine diphosphate (ADP)-activated P2Y12 receptors on thrombocytes. In their native, nonmetabolized form, both drugs were reported to act as inhibitors of ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1, CD39). CD39 catalyzes the extracellular hydrolysis of nucleoside tri- and diphosphates, mainly adenosine 5?-triphosphate (ATP) and ADP, yielding adenosine monophosphate, which is further hydrolyzed by ecto-5?-nucleotidase (CD73) to produce adenosine. While ATP has proinflammatory effects, adenosine is a potent anti-inflammatory, immunosuppressive agent. Inhibitors of CD39 and CD73 have potential as novel checkpoint inhibitors for the immunotherapy of cancer and infection. In the present study, we investigated 2-substituted thienotetrahydropyridine derivatives, structurally related to ticlopidine, as CD39 inhibitors. Due to their substituent on the 2-position, they will not be metabolically transformed into reactive thiols and can, therefore, be expected to be devoid of P2Y12 receptor-antagonistic activity in vivo. Several of the investigated 2-substituted thienotetrahydropyridine derivatives showed concentration-dependent inhibition of CD39. The most potent derivative, 32, showed similar CD39-inhibitory potency to ticlopidine, both acting as allosteric inhibitors. Compound 32 showed an improved selectivity profile: While ticlopidine blocked several NTPDase isoenzymes, 32 was characterized as a novel dual inhibitor of CD39 and CD73.
Discovery of Thieno[2,3- d]pyrimidine-Based Hydroxamic Acid Derivatives as Bromodomain-Containing Protein 4/Histone Deacetylase Dual Inhibitors Induce Autophagic Cell Death in Colorectal Carcinoma Cells
Pan, Zhaoping,Li, Xiang,Wang, Yujia,Jiang, Qinglin,Jiang, Li,Zhang, Min,Zhang, Nan,Wu, Fengbo,Liu, Bo,He, Gu
, p. 3678 - 3700 (2020/04/30)
Bromodomain-containing protein 4 (BRD4) and histone deacetylases (HDAC) are both attractive epigenetic targets in cancer and other chronic diseases. Based on the integrated fragment-based drug design, synthesis, and in vitro and in vivo evaluations, a series of novel thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives are discovered as selective BRD4-HDAC dual inhibitors. Compound 17c is the most potent inhibitor for BRD4 and HDAC with IC50 values at nanomolar levels, as well as the expression level of c-Myc, and increases the acetylation of histone H3. Moreover, 17c presents inhibitory effects on the proliferation of colorectal carcinoma (CRC) cells via inducing autophagic cell death. It also has a good pharmacokinetic profile in rats and oral bioavailability of 40.5%. In the HCT-116 xenograft in vivo models, 17c displays potent inhibitory efficiency on tumor growth by inducing autophagic cell death and suppressing IL6-JAK-STAT signaling pathways. Our results suggest that the BRD4-HDAC dual inhibition might be an attractive therapeutic strategy for CRC.
Synthesis, characterization and crystal structure of heterocyclic tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidinone derivatives via sequential aza-Wittig/base catalyzed cyclization
Chen, Hong,Liu, Ming-Guo
, p. 31 - 40 (2018/12/05)
Seventeen examples of 7-Benzyl-5,6,7,8-tetrahydropyrido [4′,3′:4,5]thieno [2,3-d]pyrimidin-4(3H) -ones were synthesized by base catalyzed reactions of nucleophilic reagents (aliphatic amines, alcohols or phenols) with carbodiimides 3, which in turn were obtained by the aza-Wittig reaction of iminophosphorane 2 with aromatic isocyanates. The compounds were fully characterized by analytical and spectroscopic techniques (FT-IR, 1H NMR, 13C NMR and MS). Crystal structure determination of three tetrahydropyrido [4′,3':4,5]thieno [2,3-d]pyrimidinone derivatives has been undertaken in order to better understanding the influence of structural modifications upon overall molecular geometry and conformation. 3D supramolecular architectures are formed in the crystals by self-assembly of the molecules via stacking interactions and various hydrogen bonds. Meanwhile, crystal structure of a guanidine intermediate 4a was characterized in order to proclaim the reaction mechanism of the base catalyzed intramolecular cycloaddition.
Synthesis and Antimicrobial Evaluation of Novel Chiral 2-Amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridine Derivatives
Rossetti, Arianna,Bono, Nina,Candiani, Gabriele,Meneghetti, Fiorella,Roda, Gabriella,Sacchetti, Alessandro
, (2019/05/15)
New N-substituted-2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridine derivatives were synthesized employing a convenient one-pot three-component method and their structures were characterized by 1H-NMR and single crystal X-ray diffraction analysis. All the synthesized compounds were in vitro screened for antimicrobial activity against Gram-positive (Sarcina lutea) and Gram-negative bacteria (Escherichia coli). In this work, we introduced a chiral residue on the tetrahydropyridine nitrogen, the hitherto the less investigated position on this pharmacophore in order to explore the effect. The antibacterial results showed that the synthesized compounds were active only against Gram-positive bacteria and the (R)-enantiomers displayed a greater antimicrobial potency than their (S)-counterparts. The structure–activity relationship here investigated may provide some interesting clues for future development of tetrahydrothienopyridine derivatives with higher antimicrobial activity.
Basic Ionic Liquid [bmIm]OH-Mediated Gewald Reaction as Green Protocol for the Synthesis of 2-Aminothiophenes
Kaki, Venkata Rao,Akkinepalli, Raghuram Rao,Deb, Pran Kishore,Pichika, Mallikarjuna Rao
, p. 119 - 126 (2015/10/20)
A simple, efficient, and environmental friendly procedure was developed based on the Gewald reaction for the synthesis of 2-aminothiophenes using a basic ionic liquid [bmIm]OH as both catalyst and solvent. Besides being a green protocol, the method offers advantages of successful synthesis of a variety of alkyl, aryl, alkoxy, and alkylamino-2-aminothiophenes in good yields.
Facile synthesis of thieno[2,3-d]pyrimidine derivatives using inorganic base catalysis
Meng, Shuangming,Jia, Zhifang,Wang, Kewei,Fan, Yueqin,Guo, Yong
supporting information, p. 1461 - 1465 (2014/05/20)
Potassium carbonate as inorganic base catalyst was used to develop an efficient synthetic procedure for the preparation of thieno[2,3-d]pyrimidine derivatives. The molecular structure of the newly synthesized compounds were confirmed by NMR spectral data.
Efficient synthesis of thieno[2,3-d]pyrimidin-4(3H)-ones by a sequential aza-Wittig reaction/base catalyzed cyclization
Dai, Zhong-Xu,Chen, Hong,Liu, Ming-Guo,Ding, Ming-Wu
scheme or table, p. 197 - 201 (2012/03/10)
7-Benzyl-5,6,7,8-tetrahydropyrido[4 ' ,3 ' :4,5]thieno[2,3-d] pyrimidin-4(3 H)-ones were synthesized by base catalyzed reactions of nucleophilic reagents (aliphatic amines, alcohols or phenols) with carbodiimides 4 , which in turn were obtained by the aza-Wittig reaction of iminophosphoranes 3 with aromatic isocyanates. 2011 · Copyright by Walter de Gruyter.
Efficient synthesis of 7-benzyl-5,6,7,8-tetrahydropyrido[4′,3′: 4,5]thieno [2,3-d]pyrimidin-4(3H)-ones via aza-Wittig reaction
Chen, Hong,Yan, Kai,Liu, Ming-Guo
experimental part, p. 644 - 647 (2012/05/31)
7-benzyl-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d] pyrimidin-4(3H)-ones were synthesized by base catalytic reactions of nucleophilic reagents (aliphatic amines, alcohols or phenols) with carbodiimides 4, which were obtained from the aza-Wittig reaction of iminophosphoranes 3 with aromatic isocyanates.
3- and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists
Aurelio, Luigi,Valant, Celine,Figler, Heidi,Flynn, Bernard L.,Linden, Joel,Sexton, Patrick M.,Christopoulos, Arthur,Scammells, Peter J.
experimental part, p. 7353 - 7361 (2010/03/03)
A series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were prepared and evaluated as potential allosteric modulators at the A1 adenosine receptor. The structure-activity relationships of the 3- and 6-positions of a series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were explored. Despite finding that 3- and 6-substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines possess the ability to recognize an allosteric site on the agonist-occupied A1AR at relatively high concentrations, the structural modifications we have performed on this scaffold favor the expression of orthosteric antagonist properties over allosteric properties. This research has identified 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as novel class of orthosteric antagonist of the A1AR and highlighted the close relationship between structural elements governing allosteric modulation and orthosteric antagonism of agonist function at the A1AR.
