89567-03-3Relevant articles and documents
2 substituted carboxamide and thienopyrimidine ketone derivative and its preparation method and application
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, (2017/11/17)
The invention relates to the technical field of pharmaceutical and organic synthesis, and specifically discloses a 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidy-4(3H)-ketone derivative and a preparation method and an application thereof. According to the invention, a structure of the 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidy-4(3H)-ketone derivative is shown by the formula (I) in the specification. The 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidy-4(3H)-ketone derivative has certain prohibitive effects on TNF-a release induced by LPS and IL-6 release, and shows good anti-inflammatory activity.
Design, synthesis, and biological activity of tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives as anti-inflammatory agents
Zhang, Yuan,Luo, Lu,Han, Chao,Lv, Handeng,Chen, Di,Shen, Guoliang,Wu, Kaiqi,Pan, Suwei,Ye, Faqing
, (2017/12/05)
We designed and synthesized 26 prototype compounds and studied their anti-inflammatory activity and underlying molecular mechanisms. The inhibitory effects of the compounds on the production of nitric oxide (NO), cytokines, inflammatory-related proteins, and mRNAs in lipopolysaccharide (LPS)-stimulated macrophages were determined by the Griess assay, Enzyme linked immunosorbent assay (ELISA), Western blot analysis, and Reverse transcription-Polymerase Chain Reaction (RT-PCR), respectively. Our results indicated that treatment with A2, A6 and B7 significantly inhibited the secretion of NO and inflammatory cytokines in RAW264.7 cells without demonstrable cytotoxicity. It was also found that A2, A6 and B7 strongly suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase enzyme COX-2, and prevented nuclear translocation of nuclear factor κB (NF-κB) p65 by inhibiting the degradation of p50 and IκBα. Furthermore, the phosphorylation of mitogen-activated protein kinase (MAPKs) in LPS-stimulated RAW264.7 cells was significantly inhibited by A2, A6 and B7. These findings suggest that A2, A6 and B7 may operate as an effective anti-inflammatory agent through inhibiting the activation of NF-κB and MAPK signaling pathways in macrophages. Moreover, rat paw swelling experiments showed that these compounds possess anti-inflammatory activity in vivo, with compound A6 exhibiting similar activities to the reference drug Indomethacin.
A Thieno[2,3- d]pyrimidine Scaffold Is a Novel Negative Allosteric Modulator of the Dopamine D2 Receptor
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)
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.
TUBULIN-BINDING COMPOUNDS, COMPOSITIONS AND USES RELATED THERETO
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, (2016/12/22)
This disclosure relates to antimitotic compounds, compositions comprising therapeutically effective amounts of these compounds, and methods of using those compounds and compositions in treating hyperproliferative disorders, e.g., cancers and myelodysplast
Synthesis and biological evaluation of novel condensed pyrimidinylmethylsulfinylbenzimidazoles as antiulcer agent
Dudhe, Prashik B.,Jain, Kishor S.,Raskar, Vikas K.,Deodhe, Atul S.,Patel, Jasminkumar G.,Phoujdar, Manisha S.,Kathiravan, Muthu K.
, p. 3719 - 3727 (2013/07/26)
Current therapies to treat gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and other acid-related diseases either prevent stimulation of the parietal cell (H2-receptor antagonists) or inhibit gastric H+/K+/s
Design, synthesis, and antihyperlipidemic evaluation of novel 2-[1-(Substitutedphenyl)-4-oxo-azetidin-2-yl]-5,6-disubstitutedthieno[2,3-d] pyrimidin-4(3H)-ones
Arya, Nikhilesh,Munde, Manoj K.,Dwivedi, Jaya,Jagdale, Archana Y.,Jain, Kishor S.
, p. 588 - 595 (2013/09/02)
Novel thienopyrimidine derivatives of azetidinone possessing the combined features of the cholesterol absorption inhibitor drug ezetimibe and potential antihyperlipidemic 2-substitutedthienopyrimidin-4-ones were synthesized and characterized by spectrosco
Convenient and efficient synthesis of some novel fused thieno pyrimidines using gewald's reaction
Nirogi, Ramakrishna V.S.,Kambhampati, Sastri Rama,Kothmirkar, Prabhakar,Arepalli, Sobhanadri,Pamuleti, Narasimha Reddy G.,Shinde, Anil K.,Dubey
, p. 2835 - 2851 (2011/09/12)
Several functionalized thienopyrimidines were synthesized by a facile synthetic method, which includes Gewald's reaction, and were characterized by spectral and analytical data. These functionalized thienopyrimidines were converted to various new chemical
A novel microwave-assisted green synthesis of condensed 2-substituted-pyrimidin-4(3H)-ones under solvent-free conditions
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
body text, p. 178 - 185 (2009/07/19)
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.
Synthesis and antihyperlipidemic activity of some novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-disubstituted pyrimidines
Kathiravan, Matthu K.,Shishoo, Chamanlal J.,Kumar, Krishnan Girish,Roy, Saroj Kumar,Mahadik, Kakasheb R.,Kadam, Shivajirao S.,Jain, Kishor S.
, p. 599 - 606 (2008/03/13)
Synthesis and antihyperlipidemic activity of a series of novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-di-substituted pyrimidines are described. The design of these compounds is based on the earlier QSAR study on the antihyperlipidemic 2-substituted
Thienopyrimidines as hetryl moiety in 2-azetidinones: Synthesis of 4-hetryl-2-azetidinones
Kanwar, Seema,Sharma
, p. 2367 - 2371 (2007/10/03)
A Facile and efficient method for the synthesis of 4-hetryl substituted β-lactams 1 have been reported from substituted thienopyrimidinone 2b, which in turn was prepared from appropriately substituted 2-amino-3-carboxamido thiophene 10. The structures of
