Heterocyclic synthesis with ω-bromoacetophenone: Synthesis of some new pyrazole, pyridazine and furan derivatives

p-Bromophenacylnitrile derivatives 3a,b react with hydrazinederivatives under different conditions to afford the diaminopyrazoles 4a,b, the pyridazine-6-imines 5a,b,and 5-aminopyrazoles 11a,b. Refluxing of 5a in ethanol/hydrochloric acid mixture furnished its transformation into the pyridazine-6-one 6 while 5b under the same reaction conditions, underwent ring contraction expelling phenyl hydrazine to afford the furan derivative 7.Compound 7 could also be obtained from 3a upon refluxin ethanol catalyzed by triethylamine. Ethyl  phenacylcyanoacetate 3b reacts with hydrazine hydrate and phenylhydrazine to afford the 4-phenacylpyrazole derivatives11a,b respectively. Compound 3b afforded a mixture ofthe two furan derivatives 12 and 13 upon reflux in ethanolcatalyzed by triethylamine. Compound 3b also undergoesthe coupling reaction with the aromatic diazoniumsalts 14a-d to afford the pyrazole derivatives 16a-d presumablyvia the hydrazo derivatives 15a-d respectively

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

New Routes to Pyridino[2,3-d]pyrimidin-4-one and Pyridino- [2,3-d]triazolino[4,5-a]pyrimidin-5-one Derivatives

Abstract: 2-Thioxopyrimidinyl-5-(N,N-dimethylamino)formamidine (5) and 1,3diphenyltriazolo[3,4-d]pyrimidinyl-N,N-dimethylformamidine (14) were prepared by condensation of 6-amino-2-thioxo-1,3-dihydropyrimidin-4-one (2) and 7-amino-1,3diphenyl-1,2,4-triazolo[4,3-a]pyrimidin-4-one (13) with dimethylformamide dimethylacetal (DMFDMA). Compound 5 reacts with acetophenone and 2-acetylthiophene to give the 2-thioxo-1,3-dihydropyridino[2,3-d]pyrimidin-4-ones 3a and 3b, respectively. Compounds 3a,b react with hydrazonoyl halides 6,7 to give pyridino[2,3-d]triazolo[4,5a]pyrimidin-4-ones 11a-d and not the isomeric structures 12a-d. Formamidines of type 14 react with ethyl cyanoacetate, malononitrile and benzoyl acetonitrile to give the 1,3diphenyl-3a-hydropyridino[2,3-d]1,2,4-triazolo[4,5-a]pyrimidin-4-one derivatives 15a,b and 18, respectively. The structures of the newly synthesized compounds are established on the basis of chemical and spectroscopic evidences as well as their synthesis by alternative methods

Michael Reactions of Arylidenesulfonylacetonitriles. A New Route to Polyfunctional Benzo[a]quinolizines

Abstract: Arylidenesulfonylacetonitriles react in acetonitrile with 1-methylisoquinoline and isoquinolin-1-yl-acetonitrile in the presence of piperidine to give benzo[a]quinolizines 6,9 and 7,10, respectively. The structures of the products were established on the basis of elemental and spectral analyses and their chemical reactivity