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Edward E Knaus - One of the best experts on this subject based on the ideXlab platform.
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synthesis and biological evaluation of 3 4 diphenyl 1 2 5 oxadiazole 2 oxides and 3 4 diphenyl 1 2 5 Oxadiazoles as potential hybrid cox 2 inhibitor nitric oxide donor agents
Bioorganic & Medicinal Chemistry, 2005Co-Authors: Carlos A Velazquez, P Praveen N Rao, Robert Mcdonald, Edward E KnausAbstract:A group of 3,4-diphenyl-1,2,5-oxadiazole-2-oxides (3,4-diphenylfuroxans) and the corresponding N-desoxy 3,4-diphenyl-1,2,5-Oxadiazoles (3,4-diphenylfurazans) analogs, were synthesized for in vitro evaluation as hybrid cyclooxygenase (COX) inhibitor/nitric oxide donor agents. Reaction of 1-[4-(methylsulfonyl)phenyl]-2-phenylethene with an aqueous sodium nitrite solution in acetic acid afforded a mixture (3:1 ratio) of the inseparable 4-[4-(methylsulfonyl)phenyl]-3-phenyl-1,2,5-oxadiazole-2-oxide (13a) and 3-[4-(methylsulfonyl)phenyl]-4-phenyl-1,2,5-oxadiazole-2-oxide (13b) regioisomers. A group of related regioisomers possessing either a p-aminosulfonylphenyl (16) or a p-azidosulfonylphenyl (17), moiety were obtained by chlorosulfonation of the unsubstituted 3,4-diphenylfuroxan (10) and subsequent reaction with either ammonium hydroxide or sodium azide, respectively. The methanesulfonyl regioisomers 13a,b [COX-1 IC50=11.6 microM; COX-2 IC50=0.12 microM; COX-2 selectivity index (SI)=97] and aminosulfonyl regioisomers 16 (COX-1 IC50=9.8 microM; COX-2 IC50=0.78 microM; COX-2 SI=12), like the reference drug celecoxib (COX-1 IC50=33.1 microM; COX-2 IC50=0.07 microM; COX-2 SI=472), were potent in vitro COX-2 inhibitors with a good COX-2 selectivity index. Release of nitric oxide (NO) from the 3,4-diphenylfuroxan compounds (10, 13a,b, 16, 17) was thiol-dependent since the % NO released was higher upon incubation in the presence of l-cysteine (0.57-3.18%) compared to that in phosphate buffer solution at pH7.4 (0.06-0.15%). Molecular modeling (docking) studies show that the methanesulfonyl (MeSO2) COX-2 pharmacophore present in regioisomers 13a,b is positioned in the vicinity of the COX-2 secondary pocket. The in vitro NO release data, COX-1/COX-2 inhibition and COX-2 SI structure-activity relationships acquired, and molecular modeling docking studies suggest that the 1,2,5-oxadiazole-2-oxide (furoxan) ring possesses beneficial features that should be present in a suitable central ring template (bioisostere) pertinent to the design novel hybrid COX-2 inhibitor/nitric oxide donor agents with a low ulcerogenicity profile that may be free from adverse cardiovascular effects.
Ian W. Davies - One of the best experts on this subject based on the ideXlab platform.
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Superior reactivity of thiosemicarbazides in the synthesis of 2-amino-1,3,4-Oxadiazoles.
The Journal of organic chemistry, 2006Co-Authors: Sarah J. Dolman, Francis Gosselin, Paul D. O’shea, Ian W. DaviesAbstract:A facile and general protocol for the preparation of 2-amino-1,3,4-Oxadiazoles is reported. This method relies on a tosyl chloride/pyridine-mediated cyclization of a thiosemicarbazide, which is readily prepared by acylation of a given hydrazide with the appropriate isothiocyanate. Cyclization of the thiosemicarbazide consistently outperforms the analogous semicarbazide cyclization under these conditions, for 18 distinct examples. Utilizing this protocol, we have prepared 5-alkyl- and 5-aryl-2-amino-1,3,4-Oxadiazoles in 78-99% yield.
Domenico Spinelli - One of the best experts on this subject based on the ideXlab platform.
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Photochemical isomerization of aryl hydrazones of 1,2,4-oxadiazole derivatives into the corresponding triazoles
'Royal Society of Chemistry (RSC)', 2012Co-Authors: Maurizio D'auria, Domenico Spinelli, Vincenzo Frenna, Salvatore Marullo, Rocco Racioppi, Felicia ViggianiAbstract:The photochemical version of the Boulton-Katritzky reaction has been studied, examining the behaviour of the arylhydrazones of 3-benzoyl-5-X-1,2,4- Oxadiazoles. The effect of several modifications of the substrates structure (the E and/or Z structures of arylhydrazones, the possible presence of substituents in the arylhydrazono moiety, and the nature of substituents at C-5 of the 1,2,4-oxadiazole ring) on the course of the photochemical rearrangement has been examined
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five to six membered ring rearrangements in the reaction of 5 perfluoroalkyl 1 2 4 Oxadiazoles with hydrazine and methylhydrazine
Journal of Organic Chemistry, 2006Co-Authors: Silvestre Buscemi, Antonio Palumbo Piccionello, Andrea Pace, Nicolò Vivona, Gianluca Giorgi, Ivana Pibiri, Andrea Mazzanti, Domenico SpinelliAbstract:The hydrazinolysis reaction of 5-perfluoroalkyl-1,2,4-Oxadiazoles with hydrazine or methylhydrazine as bidentate nucleophiles has been investigated. The reaction occurred through the addition of the bidentate nucleophile to the C(5)−N(4) double bond of the 1,2,4-oxadiazole followed by ring-opening and ring-closure (ANRORC) involving the second nucleophilic site of the reagent. This ring-closure step could involve either the original C(3) of the 1,2,4-oxadiazole (giving a five-to-five membered ring rearrangement) or an additional electrophilic center linked to it (exploiting a five-to-six membered ring rearrangement). An alternative initial nucleophilic attack may involve the additional electrophilic center linked at C(3), that is the carbonyl group, leading to the formation of the hydrazones which undergo the Boulton−Katritzky rearrangement (BKR). The chosen reaction path is a function of the used nucleophile and of the nature of the substituent at C(3). At variance with previous hypotheses, when methylhy...
Kavita Shah - One of the best experts on this subject based on the ideXlab platform.
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synthesis of novel 1 2 4 Oxadiazoles and analogues as potential anticancer agents
European Journal of Medicinal Chemistry, 2011Co-Authors: Dalip Kumar, Gautam Patel, Angela K Chavers, Kueihua Chang, Kavita ShahAbstract:A library of 3,5-disubstituted-1,2,4-Oxadiazoles 7-9 and their bioisosters, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16, were synthesized and evaluated in vitro for their anticancer potential against a panel of six human cancer cell lines. The key step in the synthesis of Oxadiazoles 7-9 involve coupling of amidoxime 6 with an appropriate carboxylic acid followed by thermal cyclization. The bioisosteres, 1,3,4-oxadiazole 14 and 1,3,4-thiadiazole 16 were prepared from the reaction of a common precursor diacylhydrazine 13 with thionyl chloride and Lawesson's reagent, respectively. The anticancer studies on the synthesized compounds revealed that presence of a cyclopentyloxy or n-butyloxy on the C-3 aryl ring and piperdin-4-yl or trichloromethyl at the C-5 position of 1,2,4-oxadiazole is essential for good activity. In particular, 1,2,4-oxadiazole 7i and analogue 1,3,4-thiadiazole 16 exhibited significant activity against DU145 (IC(50): 9.3 μM) and MDA-MB-231 (IC(50): 9.2 μM) cell lines, respectively.
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synthesis and anticancer activities of novel 3 5 disubstituted 1 2 4 Oxadiazoles
ChemInform, 2009Co-Authors: Dalip Kumar, Gautam Patel, Emmanuel O Johnson, Kavita ShahAbstract:A series of 3,5-disubstituted-1,2,4-Oxadiazoles were synthesized and evaluated for their in vitro anti-proliferative activities against various cancer cell lines. Formation of 1,2,4-oxadiazole ring was accomplished by the reaction of amidoxime with carboxylic acids. The in vitro cytotoxic effects of 3,5-disubstituted-1,2,4-Oxadiazoles have been demonstrated across a wide array of tumor cell types and a few compounds exhibited specificity towards pancreatic (3f, 3h, 3j, and 3k) and prostate (3n) cancer cells. Among the prepared 3,5-disubstituted-1,2,4-Oxadiazoles, compound 3n is the most selective (>450-fold) and compound 3p is the most cytotoxic (10 nM) against prostate cancer cell lines.
Carlos A Velazquez - One of the best experts on this subject based on the ideXlab platform.
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synthesis and biological evaluation of 3 4 diphenyl 1 2 5 oxadiazole 2 oxides and 3 4 diphenyl 1 2 5 Oxadiazoles as potential hybrid cox 2 inhibitor nitric oxide donor agents
Bioorganic & Medicinal Chemistry, 2005Co-Authors: Carlos A Velazquez, P Praveen N Rao, Robert Mcdonald, Edward E KnausAbstract:A group of 3,4-diphenyl-1,2,5-oxadiazole-2-oxides (3,4-diphenylfuroxans) and the corresponding N-desoxy 3,4-diphenyl-1,2,5-Oxadiazoles (3,4-diphenylfurazans) analogs, were synthesized for in vitro evaluation as hybrid cyclooxygenase (COX) inhibitor/nitric oxide donor agents. Reaction of 1-[4-(methylsulfonyl)phenyl]-2-phenylethene with an aqueous sodium nitrite solution in acetic acid afforded a mixture (3:1 ratio) of the inseparable 4-[4-(methylsulfonyl)phenyl]-3-phenyl-1,2,5-oxadiazole-2-oxide (13a) and 3-[4-(methylsulfonyl)phenyl]-4-phenyl-1,2,5-oxadiazole-2-oxide (13b) regioisomers. A group of related regioisomers possessing either a p-aminosulfonylphenyl (16) or a p-azidosulfonylphenyl (17), moiety were obtained by chlorosulfonation of the unsubstituted 3,4-diphenylfuroxan (10) and subsequent reaction with either ammonium hydroxide or sodium azide, respectively. The methanesulfonyl regioisomers 13a,b [COX-1 IC50=11.6 microM; COX-2 IC50=0.12 microM; COX-2 selectivity index (SI)=97] and aminosulfonyl regioisomers 16 (COX-1 IC50=9.8 microM; COX-2 IC50=0.78 microM; COX-2 SI=12), like the reference drug celecoxib (COX-1 IC50=33.1 microM; COX-2 IC50=0.07 microM; COX-2 SI=472), were potent in vitro COX-2 inhibitors with a good COX-2 selectivity index. Release of nitric oxide (NO) from the 3,4-diphenylfuroxan compounds (10, 13a,b, 16, 17) was thiol-dependent since the % NO released was higher upon incubation in the presence of l-cysteine (0.57-3.18%) compared to that in phosphate buffer solution at pH7.4 (0.06-0.15%). Molecular modeling (docking) studies show that the methanesulfonyl (MeSO2) COX-2 pharmacophore present in regioisomers 13a,b is positioned in the vicinity of the COX-2 secondary pocket. The in vitro NO release data, COX-1/COX-2 inhibition and COX-2 SI structure-activity relationships acquired, and molecular modeling docking studies suggest that the 1,2,5-oxadiazole-2-oxide (furoxan) ring possesses beneficial features that should be present in a suitable central ring template (bioisostere) pertinent to the design novel hybrid COX-2 inhibitor/nitric oxide donor agents with a low ulcerogenicity profile that may be free from adverse cardiovascular effects.