- In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies of substituted 1,2,4-oxadiazole analogues against Mycobacterium tuberculosis
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The alarming increase in multi- and extensively drug-resistant (MDR and XDR) strains of Mycobacterium tuberculosis (MTB) has triggered the scientific community to search for novel, effective, and safer therapeutics. To this end, a series of 3,5-disubstitu
- Deb, Pran Kishore,Al-Shar’i, Nizar A.,Venugopala, Katharigatta N.,Pillay, Melendhran,Borah, Pobitra
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p. 869 - 884
(2021/06/11)
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- Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway
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The present work describes an unfamiliar reaction of 5-(chloromethyl)-3-substituted-phenyl-1,2,4-oxadiazoles with KCN affording trisubstituted 1,2,4-oxadiazol-5-ylacetonitriles and their parent alkanes, namely, 1,2,3-trisubstituted-1,2,4-oxadiazol-5-ylpro
- Sa??rl?, Ak?n,Dürüst, Ya?ar
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p. 3011 - 3017
(2019/01/05)
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- Design, synthesis, and bioactivities of novel oxadiazole-substituted pyrazole oximes
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A series of novel pyrazole oxime derivatives containing a substituted oxadiazole group were designed and synthesized. The bioassay results indicated that some title compounds displayed good acaricidal and insecticidal activities against Tetranychus cinnabarinus, Aphis medicaginis, Oriental armyworm, and Nilaparvata lugens. Especially, compounds 7a, 7b, and 7c had 80%, 90%, and 90% insecticidal activities against A. medicaginis at 20 μg/mL, respectively. Interestingly, some of the designed compounds displayed wonderful fungicidal activities in vivo against cucumber Pseudoperonospora cubensis. Furthermore, compounds 7a (EC50= 4.97 μg/mL) and 7h (EC50= 0.51 μg/mL) showed excellent fungicidal activity against P. cubensis comparable or better than that of the control Pyraclostrobin (EC50= 4.59 μg/mL).
- Dai, Hong,Chen, Jia,Li, Gang,Ge, Shushan,Shi, Yujun,Fang, Yuan,Ling, Yong
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supporting information
p. 950 - 953
(2017/02/10)
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- Design, microwave assisted synthesis and characterization of substituted 1,2,4-oxadiazole analogues as promising pharmacological agents
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Microwave assisted synthesis of a series of 3,5-disubstituted-1,2,4-oxadiazole analogues (3a-j) has been achieved between 5-(chloromethyl)-3-substituted phenyl-1,2,4-oxadiazoles (2a-j) and substituted benzophenone in presence of potassium carbonate in ace
- Venugopala, Katharigatta N.
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p. 1767 - 1770
(2017/06/27)
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- Discovery and preliminary evaluation of 2-aminobenzamide and hydroxamate derivatives containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors
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Using Entinostat as a lead compound, 2-aminobenzamide and hydroxamate derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against five human cancer cell lines including U937, A549, NCI-H661, MDA-MB-231 and HCT116. 2-Aminobenzamide series of compounds (10a-10j) demonstrated the most significant inhibition against human acute monocytic myeloid leukemia cell line U937, but no or poor activities against two human lung cancer cell lines. Furthermore, the target compounds were screened for their inhibitory activities against HDAC 1, 2, and 8. 2-Aminobenzamide derivatives (10) manifested a higher selectivity for HDAC 1 over HDAC 2, but were not active against HDAC 8. In contrast, most hydroxamate derivatives (11) inhibit HDAC 8 with lower IC50 values than SAHA and Entinostat. Docking study with selected compounds 10f and 11a revealed that the compounds might bind tightly to the binding pockets in HDAC 2 and HDAC 8, respectively. The results suggest that they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting HDACs.
- Cai, Jin,Wei, Hongtao,Hong, Kwon Ho,Wu, Xiaoqing,Cao, Meng,Zong, Xi,Li, Lushen,Sun, Chunlong,Chen, Junqing,Ji, Min
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- Synthesis of novel triazoles bearing 1,2,4-oxadiazole and phenylsulfonyl groups by 1,3-dipolar cycloaddition of some organic azides and their biological activities
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1,3-Dipolar cycloaddition of 5-azidomethyl-3-p-substituted phenyl-1,2,4-oxadiazoles to phenyl vinyl sulfone and bismaleimide gives rise straightforwardly to 1-((3-(p-substituted) phenyl-1,2,4-oxadiazol-5-yl)methyl)-4-(phenylsulfonyl)-4,5-dihydro-1H-1,2,3-triazoles and bisdihydropyrrolo[3,4-d][1,2,3]triazole-4,6(3aH,5H)-diones. The structures of the new cycloadducts were elucidated by means of IR, NMR (1H, 13C, 2D), mass spectra, and physical characteristics (mp and Rfvalues). In addition, anticancer activities of the cycloadducts against MCF-7 cells were also investigated.
- Dürüst, Yaar,Karaku, Hamza,Yavuz, Muhsine Zeynep,Gepdiremen, Ali Akahan
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p. 739 - 755
(2014/12/10)
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- Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors
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Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.
- Ozcan, Sevil,Kazi, Aslamuzzaman,Marsilio, Frank,Fang, Bin,Guida, Wayne C.,Koomen, John,Lawrence, Harshani R.,Sebti, Sa?d M.
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p. 3783 - 3805
(2013/06/27)
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- PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS
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Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)
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Page/Page column 76
(2012/10/08)
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- Synthesis and anti-protozoal activity of novel dihydropyrrolo[3,4-d][1,2,3] triazoles
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1,2,4-Oxadiazole and 1,2,3-triazole containing heterocyclic compounds continue to gain interest in synthesis of chemical entities and exhibit various biological activities as anti-protozoal and anti-cancer agents. By using the principle of bioisosterism,
- Dürüst, Yaar,Karaku, Hamza,Kaiser, Marcel,Tasdemir, Deniz
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experimental part
p. 296 - 304
(2012/03/27)
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- Design, synthesis, and biological activities of novel 2-cyanoacrylates containing oxazole, oxadiazole, or quinoline moieties
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A series of novel 2-cyanoacrylates containing an oxazole, oxadiazole, or quinoline moiety were designed and synthesized, and their structures were characterized by 1H NMR and elemental analysis (or high-resolution mass spectrometry). Their herbicidal activities against four weeds were evaluated, and the result indicated that some of the title compounds showed excellent herbicidal activities against rape and amaranth pigweed in postemergence treatment at a dose of 375 g/ha. Furthermore, most of these cyanoacrylates exhibited interesting plant growth regulatory activities.
- Zhao, Qiqi,Liu, Shaohua,Li, Yonghong,Wang, Qingmin
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experimental part
p. 2849 - 2855
(2010/04/30)
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- Novel 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)-xanthine derivatives as high affinity and selective A2B adenosine receptor antagonists
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A series of new 1,3-dipropyl-8-(1-heteroarylmethyl-1H-pyrazol-4-yl)- xanthine derivatives as A2B-AdoR antagonists have been synthesized and evaluated for their binding affinities for the A2B, A 1, A2A, and A3-AdoRs. 8-(1-((3-phenyl-1,2,4- oxadiazol-5-yl)methyl)-1H-pyrazol-4-yl)-1,3-dipropyl-1H-purine-2,6(3H,7H)-dione (4) displayed high affinity (Ki = 1 nM) and selectivity for the A2B-AdoR versus A1, A2A, and A 3-AdoRs (A1/A2B, A2A/A2B, and A3/A2B selectivity ratios of 370, 1100, and 480, respectively). The synthesis and SAR of this novel class of compounds are presented herein.
- Elzein, Elfatih,Kalla, Rao,Li, Xiaofen,Perry, Thao,Parkhill, Eric,Palle, Venkata,Varkhedkar, Vaibahv,Gimbel, Art,Zeng, Dewan,Lustig, David,Leung, Kwan,Zablocki, Jeff
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p. 302 - 306
(2007/10/03)
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- The discovery of a selective, high affinity A2B adenosine receptor antagonist for the potential treatment of asthma
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Adenosine has been suggested to play a role in asthma, possibly via activation of A2B adenosine receptors on mast cells and other pulmonary cells. We describe our initial efforts to discover a xanthine based selective A2B AdoR antagonist that resulted in the discovery of CVT-5440, a high affinity A2B AdoR antagonist with good selectivity (A2B AdoR Ki = 50 nM, selectivity A1 > 200: A2A > 200: A3 > 167).
- Zablocki, Jeff,Kalla, Rao,Perry, Thao,Palle, Venkata,Varkhedkar, Vaibhav,Xiao, Dengming,Piscopio, Anthony,Maa, Tenning,Gimbel, Art,Hao, Jia,Chu, Nancy,Leung, Kwan,Zeng, Dewan
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p. 609 - 612
(2007/10/03)
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- CVT-4325: A potent fatty acid oxidation inhibitor with favorable oral bioavailability
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New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325, a potent FOXi (IC50 = 380 nM, rat mitochondria) with favorable PK properties (F = 93%, t1/2 = 13.6 h, dog). New inhibitors of palmitoyl-CoA oxidation are based on the introduction of nitrogen heterocycles in the 'Western Portion' of the molecule. SAR studies led to the discovery of CVT-4325 (shown), a potent FOXi (IC50 = 380 nM rat mitochondria) with favorable PK properties (F = 93%, t1/2 = 13.6 h, dog).
- Elzein, Elfatih,Ibrahim, Prabha,Koltun, Dmitry O.,Rehder, Ken,Shenk, Kevin D.,Marquart, Timothy A.,Jiang, Bob,Li, Xiaofen,Natero, Reina,Li, Yuan,Nguyen, Marie,Kerwar, Suresh,Chu, Nancy,Soohoo, Daniel,Hao, Jia,Maydanik, Victoria Y.,Lustig, David A.,Zeng, Dewan,Leung, Kwan,Zablocki, Jeff A.
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p. 6017 - 6021
(2007/10/03)
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