51-52-5Relevant academic research and scientific papers
Design, synthesis, and acaricidal activity of phenyl methoxyacrylates containing 2-alkenylthiopyrimidine
Hao, Shulin,Cai, Zengfei,Cao, Yangyang,Du, Xiaohua
, (2020/09/16)
A series of novel phenyl methoxyacrylate derivatives containing a 2-alkenylthiopyrimidine substructure were designed, synthesized, and evaluated in terms of acaricidal activity. The structures of the title compounds were identified by 1H NMR, 13C NMR and high-resolution mass spectra (HRMS). Compound (E)-methyl 2-(2-((2-(3,3-dichloroallylthio)-6-(trifluoromethyl)pyrimidin-4-yloxy) methyl)phenyl)-3-methoxyacr-ylate (4j) exhibited significant acaricidal activity against Tetranychus cinnabarinus (T. cinnabarinus) in greenhouse tests possessing nearly twice the larvicidal and ovicidal activity compared to fluacrypyrim. Furthermore, the results of the field trials demonstrated that compound 4j could effectively control Panonychuscitri with long-lasting persistence and rapid action. The toxicology data in terms of LD50 value confirmed that compound 4j has a relatively low acute toxicity to mammals, birds, and honeybees.
Laccase-catalyzed green synthesis and cytotoxic activity of novel pyrimidobenzothiazoles and catechol thioethers
Abdel-Mohsen,Conrad,Harms,Nohr,Beifuss
, p. 17427 - 17441 (2017/03/31)
The laccase-catalyzed reaction between unsubstituted catechol and 2-thioxopyrimidin-4(1H)-ones using aerial O2 as the oxidant delivers novel pyrimidobenzothiazoles with high yields in an aqueous solvent system under mild reaction conditions. With 4-substituted catechols, catechol thioethers are formed exclusively. The synthetic protocols developed provide a sustainable approach for these compound classes. In addition, the cytotoxicity of the products against HepG2 cell line is reported. Most compounds exhibit antiproliferative activities with IC50 values at the micromolar level. A structure-activity relationship study will facilitate the further development of these compounds as cytotoxic agents.
Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1
Piechowicz, Katarzyna A.,Truong, Eric C.,Javed, Kashif M.,Chaney, Rachelle R.,Wu, Johnny Y.,Phuan, Puay W.,Verkman, Alan S.,Anderson, Marc O.
, p. 1362 - 1368 (2016/10/09)
Transmembrane protein 16A (TMEM16A), also called Ano1, is a Ca2+ activated Cl? channel expressed widely in mammalian epithelia, as well as in vascular smooth muscle and some tumors and electrically excitable cells. TMEM16A inhibitors have potential utility for treatment of disorders of epithelial fluid and mucus secretion, hypertension, some cancers and other diseases. 4-Aryl-2-amino thiazole T16Ainh-01 was previously identified by high-throughput screening. Here, a library of 47 compounds were prepared that explored the 5,6-disubstituted pyrimidine scaffold found in T16Ainh-01. TMEM16A inhibition activity was measured using fluorescence plate reader and short-circuit current assays. We found that very little structural variation of T16Ainh-01 was tolerated, with most compounds showing no activity at 10 μM. The most potent compound in the series, 9bo, which substitutes 4-methoxyphenyl in T16Ainh-01 with 2-thiophene, had IC50 ～1 μM for inhibition of TMEM16A chloride conductance.
Synthesis of new series of pyrimido[4,5-b][1,4] benzothiazines as 15-lipoxygenase inhibitors and study of their inhibitory mechanism
Nikpour, Mohsen,Mousavian, Mina,Davoodnejad, Mahdieh,Alimardani, Maliheh,Sadeghian, Hamid
, p. 5036 - 5043 (2013/09/23)
A series of 2-substituted 4-n-propyl pyrimido[4,5-b][1,4]benzothiazines were synthesized, and evaluated as soybean 15-lipoxygenase (SLO) inhibitors. Among the synthesized compounds, 2-(4-methyl piperazinyl) analog showed the best SLO inhibition activity (IC50 = 8.9 ± 0.4 μM). To rationalize the inhibitory potency variation of the compounds, computer-assisted modeling of the enzyme-inhibitor, radical scavenging evaluation, and inhibitory mechanism analyses were performed. The results showed that in 4-alkyl pyrimido[4,5-b]benzothiazines with same 2-substituent, radical scavenging potency plays a key role in lipoxygenase inhibition.
Identification of novel, exosite-binding matrix metalloproteinase-13 inhibitor scaffolds
Roth, Joshua,Minond, Dmitriy,Darout, Etzer,Liu, Qin,Lauer, Janelle,Hodder, Peter,Fields, Gregg B.,Roush, William R.
scheme or table, p. 7180 - 7184 (2012/01/15)
Matrix metalloproteinase-13 (MMP-13) has been implicated as the protease responsible for collagen degradation in cartilage during osteoarthritis (OA). Compounds that inhibit the metalloproteinase at the Zn binding site typically lack specificity among MMP family members. Analogs of the low-micromolar lead MMP-13 inhibitor 4, discovered through high-throughput screening, were synthesized to investigate structure-activity relationships in this inhibitor series. Systematic modifications of 4 led to the discovery of MMP-13 inhibitors 20 and 24 which are more selective than 4 against other MMPs. Compound 20 is also approximately fivefold more potent as an MMP-13 inhibitor than the original HTS-derived lead compound 4.
Microwave-assisted synthesis of substituted: 2-(benzylthio)imidazo[1,2a] pyrimidin-5-ones
Soh, Chai Hoon,Lam, Yulin
experimental part, p. 286 - 291 (2010/08/20)
A microwave-assisted solid-phase synthesis of 2-(benzylthio)imidazo[1,2a] pyrimidin-5-ones has been developed. Using microwave irradiation, the reaction time was significantly reduced from a few days to 80 min. A representative set of 10 2-(benzylthio)-6,7-substituted-imidazo[1,2a]pyrimidin-5-ones was prepared. These compounds were subsequently N-alkylated and formylated in good yields.
Design and optimization of a series of novel 2-cyano-pyrimidines as cathepsin K inhibitors
Rankovic, Zoran,Cai, Jiaqiang,Kerr, Jennifer,Fradera, Xavier,Robinson, John,Mistry, Ashvin,Hamilton, Emma,McGarry, George,Andrews, Fiona,Caulfield, Wilson,Cumming, Iain,Dempster, Maureen,Waller, John,Scullion, Paul,Martin, Iain,Mitchell, Ann,Long, Clive,Baugh, Mark,Westwood, Paul,Kinghorn, Emma,Bruin, John,Hamilton, William,Uitdehaag, Joost,Zeeland, Mario van,Potin, Dominique,Saniere, Laurent,Fouquet, Andre,Chevallier, Fran?ois,Deronzier, Hortense,Dorleans, Cecile,Nicolai, Eric
scheme or table, p. 1524 - 1527 (2010/06/21)
Morphing structural features of HTS-derived chemotypes led to the discovery of novel 2-cyano-pyrimidine inhibitors of cathepsin K with good pharmacokinetic profiles, for example, compound 20 showed high catK potency (IC50 = 4 nM), >580-fold selectivity over catL and catB, and oral bioavailability in the rat of 52%.
ANTIVIRAL PYRIMIDINES
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Page/Page column 51, (2010/11/03)
Disclosed herein are novel compounds comprising substituted pyrimidines, pyrazolopyrimtdines, and imidazolopyrimidines, the syntheses thereof, and compositions thereof, including pharmaceutical compositions, comprising the novel pyrimidines, pyrazolopyrimtdines, imidazolpyrimidines and related compounds. Such compounds function to inhibit entry of viruses of the Flaviviridae family, including Hepatitis C virus (HCV), into cells that are susceptible to virus infection. These compounds are useful for the treatment, therapy and/or prophylaxis of viral diseases and infection, including HCV infection.
4-PHENYL-PYRIMIDINE-2-CARBONITRILE DERIVATIVES
-
, (2008/06/13)
The invention relates to 4-phenyl-pyrimidine-2-carbonitrile derivatives having the general formula (I) or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives as well as to the use thereof in the preparation of a medicament suitable for the treatment of osteoporosis, atherosclerosis, inflammation and immune disorders, such as rheumatoid arthritis, and chronic pain, such as neuropathic pain.
Synthesis of an AZT-HEPT hybrid and homologous AzddU derivatives
Larsen, Erik,Danel, Krzysztof,Vaaben, Gitte B.,El-Emam, Ali A.,Pedersen, Erik B.,Nielsen, Claus
, p. 417 - 421 (2007/10/03)
3′-Azido-2′,3′-dideoxyuridines 6 and their corresponding α anomers 5 were syrthesizes by condensation of silylated 6-alkyl and 5,6-dialkyl substituted uracils 2 with methyl 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-α,β-D-erythro- pentofuranoside (4). Compounds 5 and 6 were treated with tetrabutylammonium fluoride to obtain the deprotected nucleosides 7 and 8, respectively. Acta Chemica Scandinavica 1996.
