- Dibenzazepine-linked isoxazoles: New and potent class of α-glucosidase inhibitors
-
α-Glucosidase inhibition is a valid approach for controlling hyperglycemia in diabetes. In the current study, new molecules as a hybrid of isoxazole and dibenzazepine scaffolds were designed, based on their literature as antidiabetic agents. For this, a series of dibenzazepine-linked isoxazoles (33–54) was prepared using Nitrile oxide-Alkyne cycloaddition (NOAC) reaction, and evaluated for their α-glucosidase inhibitory activities to explore new hits for treatment of diabetes. Most of the compounds showed potent inhibitory potency against α-glucosidase (EC 3.2.1.20) enzyme (IC50 = 35.62 ± 1.48 to 333.30 ± 1.67 μM) using acarbose as a reference drug (IC50 = 875.75 ± 2.08 μM). Structure-activity relationship, kinetics and molecular docking studies of active isoxazoles were also determined to study enzyme-inhibitor interactions. Compounds 33, 40, 41, 46, 48–50, and 54 showed binding interactions with critical amino acid residues of α-glucosidase enzyme, such as Lys156, Ser157, Asp242, and Gln353.
- Umm-E-Farwa,Ullah, Saeed,Khan, Maria Aqeel,Zafar, Humaira,Atia-tul-Wahab,Younus, Munisaa,Choudhary, M. Iqbal,Basha, Fatima Z.
-
-
- One-Pot Regioselective Synthesis of 7-Bromo-2H-Benzo[b][1,4]Oxazin-3(4H)-One Linked Isoxazole Hybrids as Anti-Cancer Agents and Their Molecular Docking Studies
-
Abstract: Regioselective synthesis of some novel 7-bromo-2H-benzo[b][1,4]oxazin-3(4H)-one linked isoxazole hybrids via copper(I) catalyzed one-pot reaction of various aromatic aldehydes with 7-bromo-4-(prop-2-yn-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one was developed. The structures of the compounds that are synthesized are confirmed by 1H NMR, 13C NMR, and mass spectra. All the hybrids have been tested for their in vitro anticancer activity against four human cancer cell lines, including HeLa, MCF-7, A549, and PC3. Three of the compounds exhibited remarkable anticancer activity compared to standard drug etoposide. Molecular docking studies with EGFR also strengthened the in vitro anticancer activity.
- Karthik, B.,Kumar, A. Kannan,Nukala, Satheesh Kumar,Ravinder, M.,Swamy, T. Narasimha
-
p. 1269 - 1275
(2021/12/23)
-
- One-pot Synthesis of Some Novel Xanthine Derived Isoxazoles as Potent Antibacterial Agents
-
In search of better antibacterial agents, a series of novel xanthine derived 3,5-disubstituted isoxazole derivatives were synthesized (3a-3j) in one-pot using 8-chloro-1,3-dimethyl-7-(prop-2-yn-1-yl)-1H-purine-2,6(3H,7H)-dione and aromatic aldehydes and f
- Vidya
-
p. 551 - 557
(2021/02/02)
-
- A facile one-pot synthesis of 3,5-disubstituted isoxazole derivatives using hydroxy (tosyloxy) iodobenzene
-
Hydroxy (tosyloxy) iodobenzene (HTIB), a hypervalent iodine reagent, has been extensively used for oxidative transformations. We have developed a one-pot synthesis wherein aldoximes when reacted with alkynes in the presence of HTIB result in the direct formation of isoxazoles. This simple and straightforward reaction allows for ease of purification while leading to the formation of high purity 3,5-disubstituted isoxazoles in moderate yields.
- Jadhav, Ravindra D.,Mistry, Hitesh D.,Motiwala, Hashim,Kadam, Kishorkumar S.,Kandre, Shivaji,Gupte, Amol,Gangopadhyay, Ashok K.,Sharma, Rajiv
-
p. 774 - 780
(2013/08/23)
-
- Reaction of polyfluorinated cyclohexa-2,4-dienones with aryl nitrile oxides
-
Reaction of 1,3-dipolar cycloaddition of 6-chloropentafluorocyclohexa-2,4- dienone, 6-chloro-3-(pentafluorophenoxy)tetrafluorocyclohexa-2,4-dienone, and perfluoro-6-phenoxycyclohexa-2,4-dienone with aryl nitrile oxides proceeds highly stereoselectively at
- Kovtonyuk,Gatilov, Yu. V.
-
p. 1215 - 1220
(2013/10/01)
-
- Discovery, synthesis, and biological evaluation of a novel group of selective inhibitors of filoviral entry
-
Herein, we report the development of an antifiloviral screening system, based on a pseudotyping strategy, and its application in the discovery of a novel group of small molecules that selectively inhibit the Ebola and Marburg glycoprotein (GP)-mediated infection of human cells. Using Ebola Zaire GP-pseudotyped HIV particles bearing a luciferase reporter gene and 293T cells, a library of 237 small molecules was screened for inhibition of GP-mediated viral entry. From this assay, lead compound 8a was identified as a selective inhibitor of filoviral entry with an IC50 of 30 μM. To analyze functional group requirements for efficacy, a structure-activity relationship analysis of this 3,5-disubstituted isoxazole was then conducted with 56 isoxazole and triazole derivatives prepared using "click" chemistry. This study revealed that while the isoxazole ring can be replaced by a triazole system, the 5-(diethylamino)acetamido substituent found in 8a is required for inhibition of viral-cell entry. Variation of the 3-aryl substituent provided a number of more potent antiviral agents with IC50 values ranging to 2.5 μM. Lead compound 8a and three of its derivatives were also found to block the Marburg glycoprotein (GP)-mediated infection of human cells.
- Yermolina, Maria V.,Wang, Jizhen,Caffrey, Michael,Rong, Lijun L.,Wardrop, Duncan J.
-
p. 765 - 781
(2011/04/15)
-
- Design and synthesis of spiro derivatives of parthenin as novel anti-cancer agents
-
Several novel spiro derivatives of parthenin (1) have been synthesized by the dipolar cycloaddition using various dipoles viz; benzonitrile oxides, nitrones and azides with exocyclic double bond of C ring (α-methylene- γ-butyrolactone). Majority of the compounds exhibited improved anti-cancer activity compared to the parthenin, when screened for their in vitro cytotoxicity against three human cancer cell lines viz., SW-620, DU-145 and PC-3. In vivo screening of select analog revealed improved anti-cancer activity with low mammalian toxicity as compared to parthenin. The results of the cytotoxicity pattern of these derivatives reveals the SAR of these sesquiterpinoid lactones and possible role of α,β-unsaturated ketone of parthenin in inhibiting NF-kB. A mechanistic correlation of anti-cancer activity along with in vivo and western blotting experiments has been described.
- Reddy, Doma Mahendhar,Qazi, Naveed A.,Sawant, Sanghpal D.,Bandey, Abid H.,Srinivas, Jada,Shankar, Mannepalli,Singh, Shashank K.,Verma, Monika,Chashoo, Gousia,Saxena, Arpita,Mondhe, Dilip,Saxena, Ajit K.,Sethi,Taneja, Subhash C.,Qazi, Gulam N.,Sampath Kumar
-
body text
p. 3210 - 3217
(2011/07/31)
-
- Synthesis and pharmacological evaluation of 1,3,4-oxadiazole bearing bis(heterocycle) derivatives as anti-inflammatory and analgesic agents
-
A series of novel ether-linked bis(heterocycle)s have been synthesized via [3 + 2]-cycloaddition reaction of nitrile oxide with allyl alcohol followed by intramolecular 1,3-diploar cycloaddition reaction of nitrile imine with carbonyl group. All the newly
- Jayashankar,Lokanath Rai,Baskaran,Sathish
-
experimental part
p. 3898 - 3902
(2009/12/09)
-
- Anionic domino C-O-heterocyclization approach for the synthesis of 5-vinyl isoxazolines
-
5-Vinyl isoxazolines were isolated in high yields through domino nucleophilic addition-anionic C-O-heterocyclization, when allyl organometallics derived from trans-1,4-dihalobutene were reacted with nitrile oxides. Georg Thieme Verlag Stuttgart.
- Qazi, Naveed Ahmed,Singh, Parvinder Pal,Jan, Sumira,Kumar, H. M. Sampath
-
p. 1449 - 1451
(2008/02/13)
-
- Reaction of allenylmagnesium and allenylindium bromides with nitrile oxides: synthesis of novel 5-butynyl- and 5-methylisoxazoles
-
5-Butynylisoxazoles were obtained in high yields through a domino addition, C-O heterocyclization involving allenylmagnesium bromide and benzonitrile oxide in dry THF, in which the corresponding 5-methylisoxazoles were isolated in trace amounts. However, when the reactions were attempted in aqueous media using allenylindium bromide, 5-methylisoxazoles were formed as the sole products in high yields.
- Sampath Kumar,Singh, Parvinder Pal,Shafi, Syed,Reddy, Pitta Bhaskar,Shravankumar, Kankala,Reddy, Doma Mahender
-
p. 887 - 890
(2007/10/03)
-
- Design and Synthesis of a Piperazinylalkylisoxazole Library for Subtype Selective Dopamine Receptor Ligands
-
A piperazinylbutylisoxazole library was designed, synthesized and screened for the binding affinities to dopamine D2, D3, and D4 receptors. Several ligands were identified to possess high binding affinity and selectivity for the D3 and D4 receptors over the D2 receptor. Compounds 6s and 6t showed Ki values of 2.6 nM and 3.9 nM for the D3 receptor with 46- and 50-fold selectivity over te D2 receptor, respectively.
- Cha, Mi Young,Choi, Byung Chul,Kang, Kyung Ho,Pae, Ae Nim,Choi, Kung Il,Cho, Yong Seo,Koh, Hun Yeong,Lee, Hee-Yon,Jung, Daeyoung,Kong, Jae Yang
-
p. 1327 - 1330
(2007/10/03)
-
- Regioselective synthesis and side-chain metallation and elaboration of 3-aryl-5-alkylisoxazoles
-
A number of 3-aryl-5-alkylisoxazoles have been synthesized in high yields by reacting arylnitrile oxides with free enolate ions regioselectively obtained by metallation of various alkyl methyl ketones with LDA in THF at -78°C followed by dehydration. Inve
- Di Nunno, Leonardo,Scilimati, Antonio,Vitale, Paola
-
p. 2659 - 2665
(2007/10/03)
-
- Mechanism of Reaction of Isomeric Nitrolic Acids to Nitrile Oxides in Aqueous Solution
-
Both E and Z isomers of acetonitrolic acids 15 and 16 can be prepared when the OH group is protected by acetylation.Photoisomerization of the E-isomer resulted in quantitative conversion into the pure Z-isomer 16.Hydrolysis of the E-isomer 15 produced the parent nitrolic acid 14 which undergoes loss of NO2(1-) from the conjugate base at high pH.This reaction is however relatively slow suggesting base solubility and acidic reprecipitation as a method of purification of E-nitrolic acids.Deprotection of (Z)-O-acetylacetonitrolic acid by HO(1-) gives a highly reactive Z-nitrolic acid 17 which undergoes loss of NO2(1-) at a rate which precludes its detection; however the subsequent reactions of acetonitrile oxide (CH3CNO) formed were monitored.Rapid loss of NO2(1-) therefore occurs when there is assistance from an antiperiplanar lone pair on the imino nitrogen of the oximate anion.Arylnitrolic acids were also examined; these were in the E configuration 26 and therefore underwent slow loss of NO2(1-).Since NMR and IR data are unreliable for the assignment of configuration of nitrolic acids (relative to other oximes) a single crystal diffraction study was carried out on E-acetonitrolic acid 14.The large difference in reactivity observed for the E- and Z-nitrolic acids now permits strong supporting evidence for structural assignments.
- Egan, Carmel,Clery, Maurice,Hegarty, Anthony F.,Welch, Alan J.
-
p. 249 - 256
(2007/10/02)
-
- The 1,3-dipolar cycloadditions of nitrile oxides and nitrile imines to alkyl dicyanoacetates
-
The readily available alkyl dicyanoacetates 1 reacted with the 1,3-dipolar reagents arenecarbonitrile oxides 2′ and arenecarbonitrile imines 5′ to afford 1,2,4-oxadiazol and 1,2,4-triazol derivatives. The arenecarbonitrile oxides 2′ with electron-donating
- Neidlein, Richard,Sui, Zhihua
-
p. 501 - 507
(2007/10/02)
-
- SYNTHESIS OF 3-ARYL-4,5-DIHYDRO-5-HYDROXY-1,2-OXAZOLES BY REACTION OF SUBSTITUTED BENZONITRILE OXIDES WITH THE ENOLATE ION OF ACETALDEHYDE.
-
By reaction of substituted benzonitrile oxides with the enolate ion of acetaldehyde (quantitatively generated by the known cycloreversion of THF in the presence of n-butyllithium) a number of 3-aryl-4,5-dihydro-5-hydroxy-1,2-oxazoles (previously unknown or, in two cases, only synthesized by different procedures) have been isolated in high yields.Treatment of such hydroxy-isoxalines with some common bases allows their conversion in high yields into the corresponding isoxazoles.
- Di Nunno, L.,Scilimati, A.
-
p. 2181 - 2190
(2007/10/02)
-
- SYNTHESIS AND PROPERTIES OF AZOLS AND THEIR DERIVATIVES. PART II. REACTION OF N-OXIDES OF AROMATIC NITRILES WITH UNCONJUGATED NITROOLEFINES AND SOME CONVERSION OF ADDUCT OBTAINED
-
The reaction of 1,3-dipolar cycloaddition of 3-nitro-2-methylpropene-1, 3,3-dinitrobutene-1 or 3-nitropropene-1 with N-oxides of aromatic nitriles (RC6H4CN->O, R = H, m-NO2, p-NO2, p-CH3O) and likewise some chemical properties of 3-phenyl-5-nitromethyl
- Baranski, Andrzej,Shvekhgeimer, Genrikh A.,Kirillova, Natalia I.
-
-