158611-70-2Relevant academic research and scientific papers
Cu(I)-Catalysis of One-Pot Synthesis of Some Novel Regioselective Isoxazole-Benzimidazole Hybrids and Their In Vitro Anti-Cancer Evaluation
Ashok Kumar,Shanmukha Kumar Jagarlapudib
, p. 2512 - 2515 (2019)
Regioselective synthesis of some novel isoxazole-benzimidazole hybrids in high yields via Cu(I)-catalyzed tandem one-pot reaction of aromatic aldehydes with 1-prop-2-ynylbenzimidazole is developed. Structures of the synthesized compounds are confirmed by
Synthesis, antimalarial activity, and target binding of dibenzazepine-tethered isoxazolines
Vinay Kumar, Koravangala S.,Lingaraju, Gejjalagere S.,Bommegowda, Yadaganahalli K.,Vinayaka, Ajjampura C.,Bhat, Pritesh,Pradeepa Kumara, Challanayakanahally S.,Rangappa, Kanchugarakoppal S.,Gowda, D. Channe,Sadashiva, Maralinganadoddi P.
, p. 90408 - 90421 (2015/11/16)
Malaria, a complex and deadly parasitic infectious disease, is a huge public health problem in many endemic countries around the globe. The prevailing extensive resistance of malaria parasites to traditional drugs and emergence of resistance to the currently used frontline artemisinin-based chemotherapy calls for the development of new drugs. Towards this objective and since compounds containing the dibenzazepine moiety are effective in treating both gametocyte and asexual stage malaria parasites, including multi drug resistant parasites, a library of dibenzazepine tethered 3,5-disubstituted isoxazolines was synthesised via 1,3-dipolar cycloaddition reaction. An additional diversified group of dibenzazepine derivatives were accessed by Suzuki coupling of one of the above dibenzazepine derivatives with various organoboronic acids. All compounds were structurally characterized and were evaluated for their antimalarial activity. They exhibited good to excellent inhibitory activity against the growth of drug-sensitive Plasmodium falciparum 3D7 strain with IC50 values ranging from 0.2 to 7.7 μM. About 50% of the compounds were either minimally or not toxic to human cell lines. Five of the compounds (6j, 6k, 8c, 8k and 8l) that highly inhibited the parasite growth were further assessed for antimalarial activity using an additional chloroquine-sensitive (D6) and two chloroquine-resistant (W2 and 7G8) P. falciparum strains. These compounds were effective against all four strains (3D7, D6, W2 and 7G8), exhibiting IC50 values of 0.1 to 1.75 μM. The dibenzazepines were identified to target the metalloamino-peptidase of parasites. Molecular docking and dynamics simulation studies were performed to understand the binding mode and binding strengths of the selected compounds with the enzyme. In agreement with their excellent antimalarial activity, the data suggested that the compounds can strongly bind to the active site of the enzyme.
1,3-dipolar cycloaddition reaction of nitrile oxides revisited - Unusual side products characterized by 2d NMR
Gucma,Golebiewski
, p. 572 - 578 (2014/06/10)
Cycloaddition of (4-trifluoromethyl)phenylnitrile oxide to N-(4-methoxyphenyl)acrylamide afforded bicyclic tetrahydro-oxazolo-(3,2-b)[1,3] oxazine-2-carboxamide derivative in result of N-acylation of the initially formed cycloadduct by the dipolarophile.
A facile one-pot synthesis of 3,5-disubstituted isoxazole derivatives using hydroxy (tosyloxy) iodobenzene
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)
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.
Discovery, synthesis, and biological evaluation of a novel group of selective inhibitors of filoviral entry
Yermolina, Maria V.,Wang, Jizhen,Caffrey, Michael,Rong, Lijun L.,Wardrop, Duncan J.
, p. 765 - 781 (2011/04/15)
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.
A novel synthesis of N-unsubstituted β-enamino thioesters from 3-arylisoxazoles and 3-aryl-5-phenylthio-2-isoxazolines
Vitale, Paola,Di Nunno, Leonardo,Scilimati, Antonio
experimental part, p. 3195 - 3203 (2010/10/21)
A novel procedure for the synthesis of N-unsubstituted β-enamino thioesters, (Z)-S-phenyl 3-amino-3-arylprop-2-enethioates, from 3-arylisoxazoles or 3-aryl-5-phenylthio-2-isoxazolines is described and a plausible mechanism for the reaction is proposed. Some examples of conversion of one β-enamino thioester [(Z)-S-phenyl 3-amino-3-phenylprop-2-enethioate] into N-unsubstituted β-enaminoacyl derivatives (β-enamino esters, β-enamino amides, and β-keto amides) are also reported. Georg Thieme Verlag Stuttgart - New York.
Enantioselective 1,3-dipolar cycloaddition reactions using chiral lanthanide catalysts
Golebiewski, W. Marek,Gucma, Miroslaw
experimental part, p. 1687 - 1693 (2009/09/06)
(Chemical Equation Presented) Regio- and stereoselective 1,3-dipolar cycloaddition of nitrile oxides to internal 2-pentenols, α,β- unsaturated esters and amides catalyzed by R-(+) BINOL-lanthanide complexes affords corresponding 3-aryl-2-isoxazolines with
Effect of the aryl group substituent in the dimerization of 3-arylisoxazoles to syn 2,6-diaryl-3,7-diazatricyclo[4.2.0.02,5]octan-4,8-diones induced by LDA
Di Nunno, Leonardo,Vitale, Paola,Scilimati, Antonio
experimental part, p. 11198 - 11204 (2009/04/11)
3-Arylisoxazoles react with LDA in THF at 0 °C affording syn-2,6-diaryl-3,7-diazatricyclo[4.2.0.02,5]octan-4,8-diones (bis-azetidinones), via stereoselective dimerization of an azetinone anion intermediate. A?fragmentation reaction affording arylnitriles may compete with electronic and steric effects of the substituent present in the aryl group being pivotal in determining the outcome of this reaction. An interesting behaviour with LDA of arylnitriles arising from the fragmentation reaction of some 3-arylisoxazoles was also observed. N,N-Diisopropylaminobenzonitriles were in fact formed (plausibly via a benzyne mechanism) from 3-(4-chlorophenyl)isoxazole and 3-(2-chlorophenyl)isoxazole, whereas 3-(2-methylphenyl)isoquinolin-1-amine was isolated starting from 3-(2-methylphenyl)isoxazole and LDA.
Chiral ruthenium Lewis acid-catalyzed nitrile oxide cycloadditions
Brinkmann, Yasmin,Madhushaw, Reniguntala J.,Jazzar, Rodolphe,Bernardinelli, Gerald,Kündig, E. Peter
, p. 8413 - 8419 (2008/02/08)
The synthesis of the chiral ligand (R,R)-BIPHOP-F is detailed. Its coordination to a cationic cyclopentadienyl ruthenium fragment generates [Ru (acetone)(R,R)-BIPHOP-F)Cp][SbF6], a transition metal Lewis acid that catalyzes the [3+2] dipolar cy
Stereoselective dimerization of 3-arylisoxazoles to cage-shaped bis-β-lactams syn 2,6-diaryl-3,7-diazatricyclo[4.2.0.02,5]octan-4,8-diones induced by hindered lithium amides
Di Nunno, Leonardo,Vitale, Paola,Scilimati, Antonio,Simone, Laura,Capitelli, Francesco
, p. 12388 - 12395 (2008/03/13)
3-Arylisoxazoles react with hindered lithium amides giving syn 2,6-diaryl-3,7-diazatricyclo[4.2.0.02,5]octan-4,8-diones in good to fair yields. Stereochemistry of the so-obtained cage-shaped bis-β-lactams was assigned by X-ray diffraction analysis. Concerning the mechanism of formation of such hitherto unknown molecules, dimerization of an azetinone anion intermediate stereoselectively induced by Li+ chelation is suggested.
