5326-47-6Relevant academic research and scientific papers
New potential antitumor quinazolinones derived from dynamic 2-undecyl benzoxazinone: Synthesis and cytotoxic evaluation
Hekal, Mohamed H.,Abu El-Azm, Fatma S. M.
, p. 2391 - 2402 (2018)
Since the quinazoline and its derivatives have been considered as a novel class of cancer chemotherapeutic agents that show promising activity against different tumors, a new series of 6-iodo-2-undecylquinazolin-4(3H)-ones were prepared via reaction of 6-iodo-2-undecyl-4H-benzoxazin-4-one with nitrogen nucleophiles, namely, primary amines, 4-amino antipyrine, hydrazine hydrate, diamines, ethanol amine, and/or hydrazide derivatives and screened for their antitumor activity in vitro against a panel of three human tumor cell lines namely; hepatocellular carcinoma (liver) HepG2, colon cancer HCT-116, and mammary gland breast MCF-7. Compounds 14, 16, and 18 showed remarkable broad spectrum antitumor activity. All compounds were fully characterized by means of IR, MS, and 1H-NMR spectra.
Discovery of novel quinazolinones and their acyclic analogues as multi-kinase inhibitors: design, synthesis, SAR analysis and biological evaluation
El Sayed, Nehad A.,Eissa, Amal A.,El Masry, Ghada F.,Abdullah, Mohamed?M.,Arafa, Reem K.
, p. 111767 - 111786 (2016)
This work deals with the design and synthesis of some novel 6-iodo-2-(pyridin-3/4-yl)-3-substituted quinazolin-4-one derivatives 8a-l, 10a-h, 13-18 in addition to certain acyclic analogues thereof viz.9a-n and 12a-h. The molecular design strategy was based on structural analogy between the new compounds and reported quinazolines and their acyclic analogues. This design scheme led to the synthesis of 8 new intermediates and 58 new final quinazolinones. The target compounds were evaluated for their antitumor activity against a panel of nine cancer cell lines viz. breast cancer (MCF-7, MDAMB-231, MDAMB-435 and HS-578T), colon cancer (HT-29 and HCC-2998) and leukemia (CCRF-CEM, K-562 and HL-60). The quinazolinones 10a-h displayed exceptional antitumor activity and compounds 12a-h showed superior potency against MCF-7. These compounds were further subjected to in vivo study. Kinase inhibitory assay was also carried out to investigate the mechanism of action of the target compounds and they displayed the highest activity against ABL, ALK and c-RAF kinases. The 3-substituted quinazolinones 10a-h showed the highest kinase activity inhibitory potency against ABL, ALK and c-RAF with the most active compound in this study being the fluoro-3-pyridyl derivative 10a. These results are in compliance with the observed antitumor activity. Finally, a molecular modeling study was performed to interpret the potential molecular interactions of these chemotypes with the most responsive biomolecular target ABL.
Synthesis of Benzyl C-Analogues of Dapagliflozin as Potential SGLT2 Inhibitors
Aidhen, Indrapal Singh,Banerjee, Sanjay K.,Kumar, Roshan,Mukkamala, Ramesh
, (2020/03/24)
Sodium-glucose co-transporter (SGLT) inhibitors are a novel class of therapeutic agents for the treatment of type 2 diabetes based on blocking of renal reabsorption of glucose. Dapagliflozin, a C-aryl glucoside, has emerged as a successful drug in the market based on this concept. We have synthesized hitherto unreported C-benzyl glucoside analogues of Dapagliflozin carrying the same aglycon present in the drug. The synthetic strategy involves in situ generation of functionalized arylmagnesium bromide with Weinreb-amide (WA) functionality for the first time, and addition on to the 1-β-formyl-2,3,4,6-tetra-O-benzyl-D-glucopyranoside for the synthesis of a C-benzyl glucoside building block 16. The WA functionality therein enabled variation in the nature of the distal ring of biarylmethane aglycon for convenient access to other analogues. All the new compounds were screened for their sodium-glucose co-transporters (SGLT1 and SGLT2) inhibition activity using cell-based nonradioactive fluorescence glucose uptake assay. Among them, 14 with IC50: 0.64 nm emerged as the most potent SGLT2 inhibitor with the best selectivity for inhibition of SGLT2 (IC50:0.64 nm) over SGLT1 (IC50: 500 nm) as compare to Dapagliflozin. On the other hand, compound 15a exhibited moderate selectivity for inhibition of SGLT2 (IC50: 4.94 nm) over SGLT1 (IC50: 68.46 nm). These results presented herein amply demonstrate the promise of C-benzyl analogues of Dapagliflozin as novel SGLT2 inhibitors for future investigations.
Improved method for microwave-assisted synthesis of benzodiazepine-2,5-diones from isatoic anhydrides mediated by glacial acetic acid
De La Cruz, Armando,Vega-Acevedo, Carlos Alejandro,Rivero, Ignacio A.,Chávez, Daniel
, p. 1607 - 1611 (2018/06/29)
An improved and simpler method for the synthesis of benzodiazepin-2,5-diones and 7-iodobenzodiazepin-2,5-diones catalyzed by glacial acetic acid using isatoic anhydride and 6-iodoisatoic anhydride, respectively, as starting materials is reported. The target products were achieved in good yields (up to 71percent) using microwave irradiation as the activating mode of reaction in the presence of acetic acid instead of the traditional polar aprotic solvents as dimethylformamide (DMF), dimethyl sulfoxide (DMSO) or dimethylacetamide (DMAC). Moreover, relatively simple purification workup is required. The optimal temperature to obtain the benzodiazepin-2,5-dione derivatives was 130 °C, while the best irradiation time was 3 min. In addition, the methodology for the selective preparation of 6-iodoisatoic anhydride with an overall yield of 62percent is presented. Printed in Brazil-
Synthesis, biological evaluation of 2,3-disubstituted-imidazolyl/benzimidazolyl-quinazolin-4(3H)-one derivatives
Patil, Dilip A.,Surana, Sanjay J.
, p. 1125 - 1139 (2016/07/06)
A series of disubstituted-quinazolin-4(3H)-ones derivatives have been synthesized and confirmed through IR, 1H- and 13C-NMR, MS spectroscopy and elemental analysis. Synthesized compounds were screened for in vitro and in vivo anti-inflammatory using human red blood cell membrane stabilization method and carrageenan-induced rat paw edema. The antimicrobial potency was measured by disk diffusion method. The compounds with imidazole (3g) and benzimidazole nucleus (4b and 4f) displayed a significant anti-inflammatory activity by in vitro method. Moreover, the compounds 3d and 4a exhibited a significant anti-inflammatory activity in vivo. The compounds 3d, 3f and 4g were found to be active antimicrobial agents, when compared with reference drug ciprofloxacin and amphotericin B. Thus, these compounds can serve as promising leads for further biological studies.
Screening for covalent inhibitors using DNA-display of small molecule libraries functionalized with cysteine reactive moieties
Zambaldo,Daguer,Saarbach,Barluenga,Winssinger
supporting information, p. 1340 - 1351 (2016/07/21)
DNA-encoded chemical libraries are increasingly used to identify leads for drug discovery or chemical biology. Despite the resurging interest in covalent inhibitors, libraries are typically designed with synthon filtered out for reactive functionalities that can engage a target through covalent interactions. Herein, we report the synthesis of two libraries containing Michael acceptors to identify cysteine reactive ligands. We developed a simple procedure to discriminate between covalent and high affinity non-covalent inhibitors using DNA display of the library in a microarray format. The methodology was validated with known covalent and high affinity non-covalent kinase inhibitors. Screening of the library revealed novel covalent inhibitors for MEK2 and ERBB2.
Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N-O bond-forming cyclization of 2-azidobenzoic acids
Dzhons, Daria Yu.,Budruev, Andrei V.
supporting information, p. 874 - 881 (2016/07/06)
The base-mediated photochemical cyclization of 2-azidobenzoic acids with the formation of 2,1-benzisoxazole-3(1H)-ones is reported. The optimization and scope of this cyclization reaction is discussed. It is shown that an essential step of the ring closure of 2-azidobenzoic acids is the formation and photolysis of 2-azidobenzoate anions.
Synthesis of a polymerizable benzocyclobutene that undergoes ring-opening isomerization at reduced temperature
Pugh, Coleen,Baker, James S.,Storms, William K.
supporting information, p. 148 - 152 (2014/01/06)
1-Ethoxyvinylbenzocyclobutene is a substituted benzocyclobutene that undergoes radical polymerization to produce polymers that can be crosslinked at 100-150 °C. The 4- and 5-vinyl isomers are synthesized in a 1:4 ratio via a halogenated benzyne intermediate produced from anthranilic acid, followed by cycloaddition with ethyl vinyl ether and replacement of the halogen atom with a vinyl group. Georg Thieme Verlag Stuttgart · New York.
Synthesis of novel quinazolinone derivatives with methyl (E)-2-(3-methoxy)acrylate moiety
Dong, Kui-Kui,Zhou, Hua-Hong,Guo, A-Rong,Chen, Tian,Wang, Yu-Liang
, p. 1039 - 1042 (2013/05/08)
A new series of quinazolinone derivatives with methyl (E)-2-(3-methoxy) acrylate moiety have been designed and synthesized. All target compounds had been identified by 1H NMR spectrum, IR spectrum and HR-MS (high resolution mass spectrum). Three target compounds (10a, 10e, 10h) were chosen to preliminarily test the antibacterial activities, the results showed that all three target compounds exhibited antibacterial activities against three bacterial strains (Proteobacteria, Salmonella, Colibacillus).
A practical iodination of aromatic compounds by using iodine and iodic acid
Shinde, Avinash T.,Zangade, Sainath B.,Chavan, Shivaji B.,Vibhute, Archana Y.,Nalwar, Yogesh S.,Vibhute, Yeshwant B.
experimental part, p. 3506 - 3513 (2011/02/22)
This article describes simple and efficient method for the iodination of different aromatic amines, hydroxy aromatic aldehydes, hydroxy acetophenones and phenols using iodine and iodic acid in ethanol as a solvent. Notable advantages include mild reaction condition, no need of catalyst, short reaction time, simple practical procedure, giving excellent yield of the product. Copyright Taylor & Francis Group, LLC.
