Palladium-Catalyzed Cascade Approach to 12-(Aryl)indolo[1,2- c ]quin­azolin-6(5 H )-ones

A straightforward one-pot approach to the synthesis of challenging 12-arylindolo[1,2-c]quinazolin-6(5H)-ones is described. Starting from readily available o-(o-aminophenylethynyl)trifluoroacetanilides, palladium-catalyzed aminoarylation of the triple bond with ArI, ArBr, and ArN2 +BF4 – is followed by cyclization of the resulting N-trifluoro­acetyl-2-(o-aminophenyl)-3-aryl indole. This sequential reaction provides the title compounds by means of a rare elimination of trifluoromethane

The Use of Palmitoylethanolamide in the Treatment of Long COVID: A Real-Life Retrospective Cohort Study

COVID-19 can cause symptoms that last weeks or months after the infection has gone, with a significant impairment of quality of life. Palmitoylethanolamide (PEA) is a naturally occurring lipid mediator that has an entourage effect on the endocannabinoid system mitigating the cytokine storm. The aim of this retrospective study is to evaluate the potential efficacy of PEA in the treatment of long COVID. Patients attending the Neurological Out Clinic of the IRCCS Centro Neurolesi Bonino-Pulejo (Messina, Italy) from August 2020 to September 2021 were screened for potential inclusion in the study. We included only long COVID patients who were treated with PEA 600 mg two times daily for about 3 months. All patients performed the post-COVID-19 Functional Status (PCFS) scale. Thirty-three patients (10 males, 43.5%, mean age 47.8 ± 12.4) were enrolled in the study. Patients were divided into two groups based on hospitalization or home care observation. A substantial difference in the PCFS score between the two groups at baseline and after treatment with PEA were found. We found that smoking was a risk factor with an odds ratio of 8.13 CI 95% [0.233, 1.167]. Our findings encourage the use of PEA as a potentially effective therapy in patients with long COVID

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

An efficient strategy for the synthesis of 6-unsubstituted indolo[1,2-c]quinazolines is described. The Pd-catalyzed reaction of o-(o-aminophenylethynyl) trifluoroacetanilides with Ar–B(OH)2 afforded 2-(o-aminophenyl)-3-arylindoles, that were converted to 12-arylindolo[1,2-c]quinazolines by adding dimethylformamide dimethyl acetal (DMFDMA) to the reaction mixture after extractive work-up. This reaction outcome is different from the previously reported Pd-catalyzed sequential reaction of the same substrates with Ar–I, Ar–Br and ArN2+BF4−, that afforded 12-arylindolo[1,2-c]quinazolin-6(5H)-ones. Moreover, 12-unsubstituted indolo[1,2-c]quinazolines can be obtained both by reacting 2-(o-aminophenyl)indoles with DMFDMA or by sequential Pd-catalyzed reaction of o-(o-aminophenylethynyl)aniline with DMFDMA

Palladium-catalyzed C12-selective direct arylation of [1,2-c] quinazolin-6(5H)-ones

A straightforward approach to the synthesis of challenging 12-arylindolo[1,2-c]quinazolin-6(5H)-ones through the palladium-catalyzed direct arylation of N-benzyl and NH-free[1,2-c]quinazolin-6(5H)-ones with aryl bromides and chlorides is described

The role of rehabilitation and vitamin D supplementation on motor and psychological outcomes in poststroke patients

: Post-Stroke depression affects between 12% and 72% of patients who have suffered a stroke. The association between low serum levels of 25-hydroxyvitamin D (25(OH) D) and increased risk of depression is reported in both stroke and non-stroke patients. Similarly, high 25(OH) D levels might be associated with greater functional improvement during rehabilitation program.We wanted to investigate the effects of an intensive rehabilitation on poststroke outcomes. We wondered if the daily rehabilitation of motor and cognitive functions could also have an effect on mood and functional abilities in addition to or as an alternative to vitamin D supplementation.We conducted a 12-week, randomized trial, double blind, parallel, monocentric clinical trial of 40 patients undergoing intensive neuro-rehabilitation treatment at a specialized care facility for ischemic or hemorrhagic brain stroke. Participants were randomly assigned, in a 1:1 ratio, to 1 of 2 parallel groups: in the experimental group, 2000 IU/day of oral cholecalciferol was administered; in the control group patients were not taking vitamin D supplementation. Patients underwent a text evaluation to investigate psychological and motor outcomes.Significant intra-group difference in outcomes measures was found but not between control group and experimental group. In the vitamin D group, we highlighted significant differences between T0 and T1 in calcium (P < .001), vitamin D (P < .001), in Montgomery Aasberg Depression Rating Scale (P = .001), and in Functional Independent Measures (P < .001). In the health control group, we found a significant difference in calcium (P = .003), vitamin D (P < .001), Montgomery Aasberg Depression Rating Scale (P = 0.006), in general self-efficacy (P = .009), and in Functional Independent Measures (P < .001).Our results show that the beneficial effect on mood and functional recovery is mainly due to neurorehabilitation rather than vitamin D supplementation

New versus Old Oral Anticoagulants: How Can We Set the Scale Needle? Considerations on a Case Report

Ischemic stroke is a complex multifactorial disorder. Anticoagulation is a growing research area, with the main goal of preventing systemic embolization and stroke. We report the case of a 41-year-old woman with antiphospholipid syndrome who was unsuccessfully treated with Dabigatran, a new oral anticoagulant, as she developed a major stroke involving the right carotid artery, due to deep venous thrombosis with pulmonary embolism. We therefore suggest a closer monitoring of the safety and efficacy of dabigatran. Moreover, in the presence of multifactorial causes of pro-coagulation, we believe that warfarin should remain the mainstay of oral anticoagulation

Palladium-catalyzed Tsuji–Trost-type reaction of benzofuran-2-ylmethyl acetates with nucleophiles

The palladium-catalyzed benzylic-like nucleophilic substitution of benzofuran-2-ylmethyl acetate with N, S, O and C soft nucleophiles has been investigated. The success of the reaction is dramatically influenced by the choice of catalytic system: with nitrogen based nucleophiles the reaction works well with Pd2(dba)3/ dppf, while with sulfur, oxygen and carbo-nucleophiles [Pd(η3-C3H5)Cl]2/XPhos is more efficient. The regiochemical outcome shows that the nucleophilic substitution occurs only on the benzylic position of the η3-(benzofuryl)methyl complex. The high to excellent yields and the simplicity of the experimental procedure make this protocol a versatile synthetic tool for the preparation of 2-substituted benzo[b]furans