- Synthesis and anthelmintic activity of some novel (E)-2-methyl/propyl-4-(2-(substitutedbenzylidene)hydrazinyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines
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A series of some novel (E)-2-methyl/propyl-4-[(2-(substitutedbenzylidene)hydrazinyl]-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines was synthesized and characterized by adopting an appropriate synthetic scheme. The effect of electron withdrawing and
- Chitikina, Satya Sri,Buddiga, Praveen,Deb, Pran Kishore,Mailavaram, Raghu Prasad,Venugopala, Katharigatta N.,Nair, Anroop B.,Al-Jaidi, Bilal,Kar, Supratik
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- 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as inhibitors of full-length RORγt
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Retinoid-related orphan receptor gamma-t (RORγt) belongs to the nuclear receptor superfamily that takes vital roles in the development and maturation of T-helper 17 cell (Th17) and lymph-node genesis. Because Th17 cells have been proved to be major effectors in human autoimmune and inflammatory diseases, the agonists and antagonists of RORγt have been discovered as promising leads for the therapeutics of these diseases. Most of the current studies of RORγt inhibitors have been focused on ligand binding domain (LBD) of RORγt because the structure and binding pockets of LBD have been elucidated and studied in detail. Recent research elucidated that the hinge domain (HD) of RORγt was significantly involved in the SUMOylation of RORγt and thus specifically affecting T cell development but not lymph-node genesis. These discoveries highlighted the potential of HD of RORγt as the target of RORγt inhibitors that could specifically inhibit Th17-related activities without affecting lymph-node genesis. In this study, we utilized a screening system with full-length RORγt including DBD, HD and LBD to evaluate the activities of a synthesized library of tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives. We identified a potent lead compound (28) that effectively inhibited Th17 cell differentiation. Docking and structure–activity relationship (SAR) studies showed that compound 28 may not bind in the binding pocket as most of the known inhibitors, but may bind in the pocket closed to Gln223 and Leu244 in HD. Our studies showed evidence that the HD of RORγt could afford a binding pocket for Th17 specific inhibitors and this domain should be further studied to discover potent and specific RORγt inhibitors.
- Lao, Chuyu,Zhou, Xiaoqing,Chen, Huanpeng,Wei, Fengjiao,Huang, Zhaofeng,Bai, Chuan
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- Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents
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A series of eleven 4-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines were designed and synthesized and their biological activities were evaluated. Synthesis involved the Gewald reaction to synthesize ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ring, and SNAr reactions. Compound 4 was 1.6-and ~7-fold more potent than the lead compound 1 in cell proliferation and microtubule depolymerization assays, respectively. Compounds 4, 5 and 7 showed the most potent antiproliferative effects (IC50 values 50 values of 53–125 nM). Additionally, compounds 4–8, 10 and 12–13 circumvented Pgp and βIII-tubulin mediated drug resistance, mechanisms that diminish the clinical efficacy of paclitaxel (PTX). In the NCI-60 cell line panel, compound 4 exhibited an average GI50 of ~10 nM in the 40 most sensitive cell lines. Compound 4 demonstrated statistically significant antitumor effects in a murine MDA-MB-435 xenograft model.
- Doshi, Arpit,Gangjee, Aleem,Hamel, Ernest,Islam, Farhana,Mooberry, Susan L.,Quadery, Tasdique M.,Robles, Andrew J.,Zhang, Xin,Zhou, Xilin
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- Cycloalkyl thienopyrimidinone compounds as well as preparation method and application thereof
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The invention relates to a parent nucleus compound containing cycloalkyl[4,5]thieno[2,3-d]pyrimidin-4 (3H)-one, and the parent nucleus compound has the following structure shown in the specification,wherein R1, X, m and n are defined in the specification.
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Paragraph 0053-0057; 0058-0061
(2020/07/12)
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- Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation
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SHP2 phosphatase, encoded by the PTPN11 gene, is a non-receptor PTP, which plays an important role in growth factor, cytokine, integrin, hormone signaling pathways, and regulates cellular responses, such as proliferation, differentiation, adhesion migrati
- Liu, Wen-Shan,Jin, Wen-Yan,Zhou, Liang,Lu, Xing-Hua,Li, Wei-Ya,Ma, Ying,Wang, Run-Ling
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p. 759 - 774
(2019/07/17)
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- Antihelminthic activity of some 2-substituted thieno[2,3-d]pyrimidin-4-ones
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Background: One of the successful approaches for rational design of bioactive compounds is the bioisosterism strategy. Thus, the bioisosteric relation of thieno[2,3-d]pyrimidin-4-ones with quinazolines, cytosine and uracil resulted in the generation of co
- Mavrova, Anelia,Dimov, Stefan,Vuchev, Dimitar,Anichina, Kameliya,Yancheva, Denitsa
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p. 887 - 894
(2018/07/03)
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- Computer-aided identification, synthesis and evaluation of substituted thienopyrimidines as novel inhibitors of HCV replication
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A structure-based virtual screening technique was applied to the study of the HCV NS3 helicase, with the aim to find novel inhibitors of the HCV replication. A library of ~450000 commercially available compounds was analysed in silico and 21 structures were selected for biological evaluation in the HCV replicon assay. One hit characterized by a substituted thieno-pyrimidine scaffold was found to inhibit the viral replication with an EC50value in the sub-micromolar range and a good selectivity index. Different series of novel thieno-pyrimidine derivatives were designed and synthesised; several new structures showed antiviral activity in the low or sub-micromolar range.
- Bassetto, Marcella,Leyssen, Pieter,Neyts, Johan,Yerukhimovich, Mark M.,Frick, David N.,Brancale, Andrea
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- Synthesis and pharmacological evaluation of novel thienopyrimidine and triazolothienopyrimidine derivatives
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Novel tricyclic thienopyrimidines (2, 3, 5, 8) and triazole-fused tetracyclic thienopyrimidines (6a-c and 9a-c) were synthesized from the precursor 2-Amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile (1). The structures of newly synthesized compounds were established by spectral and analytical data. The title compounds were screened for analgesic, anti-inflammatory, ulcerogenicity index, and antibacterial activities. Test compounds exhibited significant activity, the compounds (6a-c) and (9a-c) showed more potent analgesic activity, and the compounds (6c) and (9c) showed more potent anti-inflammatory activity than the reference standard Diclofenac Sodium. All the synthesized compounds exhibited remarkable antibacterial activity.
- Mulla, Jameel Ahmed S.,Khazi, Mohammed Iqbal A.,Panchamukhi, Shridhar I.,Gong, Young-Dae,Khazi, Imtiyaz Ahmed M.
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p. 3235 - 3243
(2014/05/06)
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- Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin- 4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2
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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.
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p. 870 - 876
(2011/04/22)
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- Synthesis and theoretical studies on energetics of novel N- and O- perfluoroalkyl triazole tagged thienopyrimidines - Their potential as adenosine receptor ligands
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A series of novel N- and O- perfluoroalkyl triazole tagged thienopyrimidines 6a-c and 7a-d was synthesized in two steps from thienopyrimidin-4-ones 2 through O- and N-propargylated regioisomers 3a-i and 4a-i respectively. Compound 2 was reacted with propargyl bromide to form O- and N-propargylated regioisomers 3 and 4 in definite proportions. Each regioisomer was separated and independently subjected to [3?+?2] cycloaddition using perfluoroalkyl azides through Click reaction under Sharpless conditions and obtained exclusively anti product in each case. The formation of two regioisomers in the first step and single anti addition product in the next step could be explained based on computational studies carried out at B3LYP/6-31G(d) level of theory. Results of Fukui function indices at the reactive centers are in accordance with the observations. On evaluation of the synthesized molecules for their binding affinities towards adenosine receptors, 4d and 4f were found to be selective to A1 over A2A receptors.
- Sirisha,Narsaiah,Yakaiah,Gayatri,Sastry, G. Narahari,Prasad, M. Raghu,Rao, A. Raghuram
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p. 1739 - 1745
(2010/06/17)
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- A novel microwave-assisted green synthesis of condensed 2-substituted-pyrimidin-4(3H)-ones under solvent-free conditions
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A rapid microwave-assisted green chemical synthesis of condensed 2-substituted-pyrimidin-4(3H)-ones 3, 4, and 5 involving the condensation of a variety of nitriles with o-aminoesters of thiophene 2a-e, benzene 2f, dimethoxybenzene 2g and quinazolinone 2h in the presence of catalytic amount of HCl alone or with the Lewis acid AlCl3 under solvent-free conditions, is described for the first time. This novel and clean one-pot methodology, which is characterized by very short reaction times and easy workup procedures, can be exploited to generate a diverse library of condensed pyrimidine heterocycles.
- Jain, Kishor S.,Bariwal, Jitender B.,Phoujdar, Manisha S.,Nagras, Madhuri A.,Amrutkar, Rakesh D.,Munde, Manoj K.,Tamboli, Riyaj S.,Khedkar, Samrat A.,Khiste, Rahul H.,Vidyasagar, Nikhil C.,Dabholkar, Vinit V.,Kathiravan
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p. 178 - 185
(2009/07/19)
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- Multistep, microwave assisted, solvent free synthesis and antibacterial activity of 6-substituted-2,3,4-trihydropyrimido[1,2-c]9,10,11,12- tetrahydrobenzo[b]thieno[3,2-e]pyrimidines
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A novel, efficient, microwave assisted route for the synthesis of 6-substituted-2,3,4-trihydropyrimido[1,2-c]-9,10,11,12-tetrahydrobenzo[b] thieno[3,2-e]pyrimidines in good yields has been developed. The intermediates, 2-substituted-4-[3-hydroxy(propyl-1-
- Raghu Prasad, Mailavaram,Pran Kishore, Deb
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p. 776 - 779
(2008/02/08)
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- Utility of a 2-Aminothiophene-3-carboxamide in the synthesis of thienopyridines and thienopyrimidines
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The article discussed about the utility of a 2-aminothiophene-3-carboxamide in the synthesis of Theinopyridines and theinopyrimidines. The reactivity of the compound toward a variety of chemical reagents was studied. The reaction mixture was evaporated in vacuo and triturated with cold water, whereby the resulting solid product was collected by filtration and crystallized from the proper solvent.
- Mohareb, Rafat M.,Sherif, Sherif M.,Gaber, Hatem M.,Ghabrial, Sami S.,Aziz, Susan I.
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p. 459 - 467
(2007/10/03)
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- Microwave-Assisted Synthesis of Novel 5-Substituted-2,3-dihydroimidazo[1,2-c]thieno[3,2-e]pyrimidines
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A novel, facile microwave-assisted route for the synthesis of imidazo[1,2-c]thieno[3,2-e]pyrimidines 4 in quantitative yields is reported. The intermediates 4-chlorothieno[2,3-d]pyrimidines 3 were synthesized under one-pot reaction conditions.
- Prasad, Mailavaram Raghu,Rao, Akkinepalli Raghu Ram,Rao, Pamulaparthi Shanthan,Rajan, Kombu Subramanian
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p. 2119 - 2123
(2007/10/03)
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- Synthesis of fused pyrimidinones by reaction of aminoarene-carboxamide with esters; Preparation of pyrrolo[2,3-d]-, thieno[2,3-d]-, isoxazolo[5,4-d]- and 1,2,3-triazolo[4,5-d]pyrimidinones, and quinazolones
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Several fused pyrimidinones were synthesized by reaction of aminoarenecarboxamide with esters in moderate to good yields. In the presence of sodium ethoxide, treatments of 2-amino-l-phenyl-3-pyrrolecarboxamide(4, 5, and 6), 2-amino-3-thiophenecarboxamide (14), 3-amino-4-isoxazolecarboxamide (10 and 11), 4-amino-1,2,3-triazole-5-carboxamide (16), and o-aminobenzamide (18) with esters (3) such as ethyl formate (3a) and ethyl acetate (3b) led to the corresponding pyrrolo[2,3-d]- (7, 8, and 9), and thieno[2,3-d]pyrimidin-4(3H)-ones (15), isoxazolo[5,4-d]pyrimidin-4(5H)-ones (12 and 13), 1,2,3-triazolo[4,5-d]pyrimidin-7(6H)-ones (17), and 4(3H)-quinazolones (19), respectively.
- Miyashita, Akira,Fujimoto, Katsuhiro,Okada, Tomomi,Higashino, Takeo
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p. 691 - 699
(2007/10/03)
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- Thieno[2.3-d]-4-pyrimidones: Synthesis, structure and pharmacological properties
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The cyclization of 2-amino-3-carbethoxy or -carboxamido thophenes yields substituted or unsubstituted 4-pyrimidones. Their structure and their 'lactam-lactam' tautomerism have been investigated by i.r. spectroscopy. The eighteen compounds synthesized were tested for a few pharmacological activities. They have no anti-edema activity except for two. Ten of them have shown an analgesic activity equal or superior to that of acetyl salicylic acid.
- Perrissin,Favre,Luu-Duc,et al.
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p. 420 - 424
(2007/10/02)
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- Synthesis and Biological Activity of Tetrazolothienopyrimidines
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4-Hydrazinothienopyrimidines (VI) undergo cyclization with nitrous acid to give tetrazolothienopyrimidines (VII).The latter compounds have been screened for their analgesic and antiinflammatory activities.
- Shishoo, C. J.,Devani, M. B.,Karvekar, M. D.,Ullas, G. V.,Ananthan, S.,et al.
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p. 666 - 668
(2007/10/02)
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- Reaction of Nitriles under Acidic Conditions. Part I. A General Method of Synthesis of Condensed Pyrimidines
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Nitriles are known to give rise to salts of different compositions with halogen acids.Many of the reactions undergone by nitriles under the influence of halogen acids are, in many cases, assumed to proceed via the intermediate formation of highly reactive
- Dave, K. G.,Shishoo, G. J.,Devani, M. B.,Kalyanaraman, R.,Ananthan, S.,et. al.
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p. 1497 - 1500
(2007/10/02)
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