- Novel N-Substituted oseltamivir derivatives as potent influenza neuraminidase inhibitors: Design, synthesis, biological evaluation, ADME prediction and molecular docking studies
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The discovery of novel potent neuraminidase (NA) inhibitors remains an attractive approach for treating infectious diseases caused by influenza. In this study, we describe the design and synthesis of novel N-substituted oseltamivir derivatives for probing the 150-cavity which is nascent to the activity site of NA. NA inhibitory studies showed that new derivatives demonstrated the inhibitory activity with IC50 values at nM level against NA of a clinical influenza virus strain. Moreover, the in silico ADME predictions showed that the selected compounds had comparable properties with oseltamivir carboxylate, which demonstrated the druggablity of these derivatives. Furthermore, molecular docking studies showed that the most potent compound 6f and 10i could adopt different modes of binding interaction with NA, which may provide novel solutions for treating oseltamivir-resistant influenza. Based on the research results, we consider that compounds 6f and 10i have the potential for further studies as novel antiviral agents.
- Ye, Jiqing,Yang, Xiao,Xu, Min,Chan, Paul Kay-sheung,Ma, Cong
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- Non-peptide-based new class of platelet aggregation inhibitors: Design, synthesis, bioevaluation, SAR, and in silico studies
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A series of 2-oxo-2-phenylethylidene linked 2-oxo-benzo[1,4]oxazine analogues 17a–x and 18a–o, incorporated with a variety of electron-withdrawing as well as electron-donating groups at ring A and ring C, were synthesized under greener conditions in excel
- Jaiswal, Pradeep K.,Sharma, Vashundhra,Kumar, Surendra,Mathur, Manas,Swami, Ajit K.,Yadav, Dharmendra K.,Chaudhary, Sandeep
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- A class of 1, 5 - diphenyl pyrazole - 3 - carboxylic acid compound and use thereof
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The invention provides a 1, 5-diphenyl pyrazol-3-carboxylic acid compound and application thereof. The compound has a structure as shown in general formula I, wherein R1 is selected from -H, halogen, saturated alkyl of C1-C6, or -X1-R4; R2 is selected from H, halogen, saturated alkyl of C1-C6, or -X2-R5; R3 is selected from H, -NH2 or -NH-CO-Ph-(o, m, p)R6; R6 is selected from H, halogen, saturated alkyl of C1-C6, or -O-R7; X1 and X2 are respectively selected from O or S independently; R4, R5 and R7 are respectively selected from H, saturated alkyl of C1-C6, benzyl or phenyl substituted by saturated alkyl of C1-C6 independently. The compound provided by the invention simulates BH3-only and p53TAD protein alpha-helix at the same time, competitively binds and antagonize Mcl-1, Bcl-2 and MDM2 protein, and specifically causes tumor cell apoptosis, thereby realizing application as an anticancer compound. (general formula I).
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Paragraph 0139; 0141
(2017/10/31)
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- HISTONE DEMETHYLASE INHIBITORS
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Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.
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Paragraph 00458; 00459
(2014/06/24)
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- Synthesis of novel dansyl-labeled Celecoxib derivatives
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Four novel dansyl-labeled derivatives of Celecoxib, a cyclooxygenase-2 (COX-2) selective inhibitor, were designed and synthesized. To realize the fluorophore-linker-approach divergent and convergent synthetic strategies were applied. Therefore Celecoxib p-benzoic acid, 8, was synthesized in a new and convenient way. The yield and the synthetic route to Celecoxib, 1, its pyrazolylic acid, 7, and its pyrazolylic methyl ester, 6, were improved. Through a convenient synthesis 1,11-diamino-3,6,9-trioxundecane, 19, was obtained in high yield and purity and used as a linker for the dansyl moiety.
- Lill, Andreas,Scholich, Klaus,Stark, Holger
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supporting information
p. 6682 - 6686
(2013/11/19)
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- Synthesis and anticancer activity of heteroaromatic linked 4β-amido podophyllotoxins as apoptotic inducing agents
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A series of different heteroaromatic linked 4β-amidopodophyllotoxin conjugates (16a-i, 17a-i and 18a-d) were synthesized and evaluated for anticancer activity against five human cancer cell lines. Among the series, one of the compound 17g showed significant antiproliferative activity in A549 (lung cancer) cell line. Flow cytometric analysis showed that 17g arrested the cell cycle in the G2/M phase leading to caspase-3 dependent apoptotic cell death. Further, Hoechst 33258 staining and DNA fragmentation assay also suggests that 17g induces cell death by apoptosis.
- Kamal, Ahmed,Tamboli, Jaki R.,Vishnuvardhan,Adil,Nayak, V. Lakshma,Ramakrishna
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p. 273 - 280
(2013/02/25)
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- Synthesis and evaluation of analgesic, anti-inflammatory, and anticancer activities of new pyrazole-3(5)-carboxylic acid derivatives
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In this article, we synthesized a series of novel 1-benzyl-5(3)-p-tolyl-1H- pyrazole-3(5)-carboxylic acid derivatives and characterized by IR, 1H NMR, and mass spectroscopy. Compounds were evaluated for their in vivo analgesic and anti-inflammatory activity using the p-benzoquinone-induced writhing test and the carrageenan-induced paw edema model, respectively. Out of 14 compounds tested, 7a, 7c, 7e, 7f, 7i, 8a-b, and 8f-g exhibited potent analgesic and/or anti-inflammatory activity as compared to reference drugs aspirin and indomethacin. Anticancer activity of these compounds was assessed against five cancer cell lines with the MTT assay (HL-60, human promyelocytic leukemia cells; HeLa, human cervical cancer cells; Raji, human B lymphocyte cell line; MCF7, human breast adenocarcinoma cell line; MDA-MB-231, estrogen-independent human breast cancer cell line). Compounds 7a, 8a, and 8b with high anti-inflammatory activity, and also 7d and 7j with mild anti-inflammatory activity exhibited promising anticancer activity against some selected cell lines.
- Caliskan, Burcu,Yilmaz, Akin,Evren, Ilker,Menevse, Sevda,Uludag, Orhan,Banoglu, Erden
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p. 782 - 793
(2013/04/10)
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- Anthranilamide-Pyrazolo[1,5-a]pyrimidine Conjugates as p53 Activators in Cervical Cancer Cells
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A library of new anthranilamide-pyrazolo[1,5-a]pyrimidine conjugates were designed, synthesized, and evaluated for their anticancer activity in cervical cancer cells such as HeLa and SiHa that possess low levels of p53. All 24 conjugates showed antiproliferative activity, while some of them exhibit significant cytotoxicity. In assays related to cell-cycle distribution, these conjugates induced G2/M arrest in HeLa cells and G1 cell-cycle arrest in SiHa cells. Immunocytochemistry assays revealed that these compounds cause nuclear translocation of p53, thereby indicating the activation of p53. In cervical cancer cells, the p53 protein is degraded by E6 oncoprotein. Immunoblot and RT-PCR analyses proved the presence of mitochondria-mediated apoptosis with involvement p53 target genes such as BAX, Bcl2, and p21 (CDKI). Moreover, these compounds increased the phosphorylated forms of p53 and provide signals for apoptosis induction. Interestingly, one of the conjugates, (2-phenyl-7-(3,4,5-trimethoxyphenyl)pyrazolo[1,5-a]pyrimidin-5-yl)(4-(2-(thiophen-2-ylmethylamino)benzoyl)piperazin-1-yl)methanone, is the most promising candidate in this series and has the potential to be taken up for further detailed studies.
- Kamal, Ahmed,Tamboli, Jaki R.,Ramaiah, M. Janaki,Adil,KoteswaraRao,Viswanath,Mallareddy, Adla,Pushpavalli,Pal-Bhadra, Manika
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scheme or table
p. 1453 - 1464
(2012/11/07)
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