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Benzimidazoles and benzimidazolones can be efficiently synthesized via acid‐catalyzed rearrangements of 3‐aroylquinoxalin‐2‐ones with various nucleophiles. The detailed mechanisms of typical rearrangements of 3‐benzoylquinoxalin‐2‐one (1 Q) with 1,2‐benzendiamine (1 a, Type I) and with methyl 3‐aminocrotonate (1 b, Type II) in acetic acid solution are explored by extensive DFT calculations. Acetic acid acts as proton source and efficient proton shuttle during the catalysis. The former rearrangement is initiated by site‐selective N⋅⋅⋅C condensation at protonated benzoyl site of 1 Q, while the latter is initiated by two competing C⋅⋅⋅C nucleophilic additions at protonated imine and benzoyl sites of 1 Q that eventually leads to two isomeric products. Both rearrangements proceed via intramolecular SN(ANRORC) mechanism (sequential Addition of Nucleophile, Ring‐Opening and Ring‐Closing) involving spiro‐quinoxalinone intermediates, but with fundamentally different RORC steps via ring‐opening anilide cation and isocyanate cation species, respectively. A simple energetic rule is suggested to determine the type of rearrangement by counting the conjugated π‐electrons within the spiro‐forming ring that may stabilize the ring‐opening anilide cation species, which may enable further rational design of novel spiro‐quinoxalinone based rearrangements. [ABSTRACT FROM AUTHOR]

The new α,α′‐diimine ligands with benzimidazole moiety were synthesized based on the rearrangement of 3‐aroylquinoxalin‐2(1H)‐ones when exposed to 4,5‐diamino‐2,1,3‐benzoxadiazole, 4,5‐diamino‐2,1,3‐benzothiadiazole and 5,6‐diaminoquinoxaline. Among them, we report the first examples of the new heterocyclic system namely benzo[4′,5′]imidazo[1′,2′:1,2]quinolino[3,4‐b and 4,3‐b][1,2,5]oxadiazolo[3,4‐f]quinoxalines, which exhibits an interesting electrochemical behavior. All compounds were fully characterized by IR, 1H and 13C NMR spectroscopies, and mass spectrometry. [ABSTRACT FROM AUTHOR]

Facile and efficient methods for the synthesis of 3‐benzylquinoxalin‐2(1H)‐ones and thiazolo[3,4‐a]quinoxalin‐4(5H)‐ones by the reaction of the readily available 3‐(α‐chlorobenzyl)quinoxalin‐2(1H)‐ones and thiourea have been developed, with multiple roles of the latter. Possible mechanisms are discussed. These two‐step sequences can be performed in a one‐pot manner to produce the desired products in moderate to high yields. [ABSTRACT FROM AUTHOR]

In pediatric low‐grade gliomas not amenable to complete resection, various chemotherapy regimens are the mainstream of treatment. An excellent overall survival of these patients makes justification of the intensification of chemotherapy difficult and calls for the development of new strategies. Bevacizumab, a humanized monoclonal antibody directed against Vascular endothelial growth factor (VEGF), has been successfully used in combination with irinotecan in a number of adult and pediatric studies and reports. Fifteen patients at median age of 7 years old (range 3 months to 15 years) were treated with bevacizumab in combination with conventional low‐toxicity chemotherapy. The majority had chiasmatic/hypothalamic and midline tumors, seven had confirmed BRAF pathway alterations including neurofibromatosis type 1 (2). Fourteen patients had more than one progression and three had radiotherapy. No deaths were documented, PFS at 11 and 15 months was 71.5% ± 13.9% and 44.7% ± 17.6% respectively. At the end of follow‐up 40% of patients has radiologically stable disease, three patients progressed shortly after completion of bevacizumab and two showed mixed response with progression of cystic component. Rapid visual improvement was seen in 6/8 patients, resolution of endocrine symptoms in 2/4 and motor function improvement in 4/6. No relation between histology or BRAF status and treatment response was observed. Treatment‐limiting toxicities included grade 4 proteinuria (2) and hypertension (2) managed with cessation (1) and pausing of therapy plus antihypertensives (1). In conclusion, bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity. This study demonstrates that anti‐VEGF humanized monoclonal antibody bevacizumab is well tolerated and can be effectively used in pediatric patients with unresectable or progressive low‐grade glioma in combination with a number of conventional chemotherapies. Addition of bevacizumab to chemotherapy does not increase toxicity and allows for rapid control of clinical symptoms. However, optimal duration of therapy is yet to be determined in future studies. [ABSTRACT FROM AUTHOR]

Background: The determinants of outcomes for adult survivors of pediatric low-grade glioma (PLGG) are largely unknown.Methods: This study collected population-based follow-up information for all PLGG patients diagnosed in Ontario, Canada from 1985 to 2012 (n = 1202) and determined factors affecting survival. The impact of upfront radiation treatment on overall survival (OS) was determined for a cohort of Ontario patients and an independent reference cohort from the Surveillance, Epidemiology, and End Results database.Results: At a median follow-up of 12.73 years (range, 0.02-33 years), only 93 deaths (7.7%) were recorded, and the 20-year OS rate was 90.1% ± 1.1%. Children with neurofibromatosis type 1 had excellent survival and no tumor-related deaths during adulthood. Adverse risk factors included pleomorphic xanthoastrocytoma (P < .001) and a thalamic location (P < .001). For patients with unresectable tumors surviving more than 5 years after the diagnosis, upfront radiotherapy was associated with an approximately 3-fold increased risk of overall late deaths (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.6-6.6; P = .001) and an approximately 4-fold increased risk of tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = .013). In a multivariate analysis, radiotherapy was the most significant factor associated with late all-cause deaths (HR, 3.0; 95% CI, 1.3-7.0; P = .012) and tumor-related deaths (HR, 4.4; 95% CI, 1.3-14.6; P = 0.014). A similar association between radiotherapy and late deaths was observed in the independent reference cohort (P < .001). In contrast to early deaths, late mortality was associated not with PLGG progression but rather with tumor transformation and non-oncological causes.Conclusions: The course of PLGG is associated with excellent long-term survival, but this is hampered by increased delayed mortality in patients receiving upfront radiotherapy. These observations should be considered when treatment options are being weighed for these patients. [ABSTRACT FROM AUTHOR]

The reaction of 3-ethoxycarbonylmethylene-3,4-dihydroquinoxalin-2(1 H)-one 5 with the Vilsmeier reagent, the treatment of 3-(3,4-dihydroquinoxalin-2(1 H)-on-3-yl)-1,2-dihydro-1,5-benzodiazepin-2(1 H)-one hydrochloride 7 with 10% and 3-benzimidazoylquinoxaline-2(1 H)-one 3 with both 1,2-phenylenediamine dihydrochloride, and the reactions of 1,2-phenylenediamine have been reinvestigated, and the structures of these reaction products have been revised. The aforementioned reactions have been shown to proceed with the formation of 1- N, N-dimethylaminomethylene-2-oxo-1,2-dihydrofuro[2,3- b]quinoxaline 10 in the first case, the formation of 3-[2-(benzimidazol-2-on-1-yl)vinyl]-1 H-quinoxalin-2-one 12 in the second case, and the formation of 2,3-bis-(1 H-benzimidazol-2-yl)quinoxaline 17 in the third case and not the formation of 3-( N, N-dimethylaminocarbonyl)furo[2,3- b]quinoxaline hydrochloride 6, the free base of 3-(3,4-dihydroquinoxalin-2(1 H)-on-3-yl)-1,2-dihydro-1,5-benzodiazepin-2(1 H)-one 7, that is, compound 11 and benzodiazepine derivative 4, as has been described earlier. In the third case, the formation of 2,3-bis-(1 H-benzimidazol-2-yl)quinoxaline 17 occurs according to the novel quinoxalin-2(1 H)-one benzimidazole discovered by us. The potential mechanisms for the investigated reactions are discussed. [ABSTRACT FROM AUTHOR]

The article presents the process to accomplish the use of rearrangement reaction on quinoxalines when exposed to enamines generated from ketones and ammonium acetate and describes the chemical equations of the process.

The rearrangement process includes a novel ring contraction as the key step to produce various benzimidazole structures bearing a pyrrole part at one of the nitrogens. [ABSTRACT FROM AUTHOR]

Review: 131 refs. [ABSTRACT FROM AUTHOR]