Structural problems posed by reactions of thiocyanates with malonyl chloride.

Malonyl Chloride reacts with alkyl and aryl thiocyanates yielding 2-alkyl- (or aryl) thio-7-chloro-4-5-dioxopyrano[3,4-e]-3-oxazines (I). These react stepwise with amines, undergoing replacement of the thio group and then of the chloro substituent. Next, the pyrone ring is opened and finally the oxazine ring, to yield N-substituted beta-aminoglutacondiamides having an alpha-carboxyureido side chain. The intermediate 2-7-diamino-4,5-dioxopyrano[3,4-e]I,3-oxazines (some of which are tautomeric) suffer oxazine ring scission with amine hydrochloride and yield substituted 4,6-diaminopyran-2-one-3-carboxyureides. The parent product (I) with amine hydrochloride retains the sulphur group and yields 4,6-diaminopyrone-3-carboxythiourethanes. However, the reactions of the parent product (I) with water and alcohol gave several quite unexpected products. From the reaction of compounds (I) with water (1 mol.) at 80°C the 6-Amino-3-thioester-2 pyrones (2) were obtained. Whilst in the presence of hydrogen chloride, 4-chloro-6-N-(substituted) thiocarboxyamido 2-pyrones resulted. Boiling water (2 mols) with compounds (I) gave 4-chloro-2,6-dihydroxypyridins, also obtained similarly from the compounds (2). 4-Chloro-2,6-dihydroxypyridine-3carboxylic esters arose when compounds (I) or (2) were refluxed with alcohols. With alcohols at ambient temperature the compounds (I) underwent replacement of the S-alkyl group by alkoxyl, but under reflux with I mol of alcohol two isomers C[7]H[2]C1NO[4](SR)OR[I] were formed. The structures of these and other products were elucidated by chemical and physical means, especially [1]H and [13]C NMR and mass spectrometry. Possible reaction mechanisms are discussed and some use has been made of specific carbon-13 labelling

Structural problems posed by reactions of thiocyanates with malonyl chloride.

Malonyl Chloride reacts with alkyl and aryl thiocyanates yielding 2-alkyl- (or aryl) thio-7-chloro-4-5-dioxopyrano[3,4-e]-3-oxazines (I). These react stepwise with amines, undergoing replacement of the thio group and then of the chloro substituent. Next, the pyrone ring is opened and finally the oxazine ring, to yield N-substituted beta-aminoglutacondiamides having an alpha-carboxyureido side chain. The intermediate 2-7-diamino-4,5-dioxopyrano[3,4-e]I,3-oxazines (some of which are tautomeric) suffer oxazine ring scission with amine hydrochloride and yield substituted 4,6-diaminopyran-2-one-3-carboxyureides. The parent product (I) with amine hydrochloride retains the sulphur group and yields 4,6-diaminopyrone-3-carboxythiourethanes. However, the reactions of the parent product (I) with water and alcohol gave several quite unexpected products. From the reaction of compounds (I) with water (1 mol.) at 80°C the 6-Amino-3-thioester-2 pyrones (2) were obtained. Whilst in the presence of hydrogen chloride, 4-chloro-6-N-(substituted) thiocarboxyamido 2-pyrones resulted. Boiling water (2 mols) with compounds (I) gave 4-chloro-2,6-dihydroxypyridins, also obtained similarly from the compounds (2). 4-Chloro-2,6-dihydroxypyridine-3carboxylic esters arose when compounds (I) or (2) were refluxed with alcohols. With alcohols at ambient temperature the compounds (I) underwent replacement of the S-alkyl group by alkoxyl, but under reflux with I mol of alcohol two isomers C[7]H[2]C1NO[4](SR)OR[I] were formed. The structures of these and other products were elucidated by chemical and physical means, especially [1]H and [13]C NMR and mass spectrometry. Possible reaction mechanisms are discussed and some use has been made of specific carbon-13 labelling

Efficacy and safety of vaginal CO2Laser treatment in female stress urinary incontinence

Background: Urinary incontinence (UI) is a common disorder that affects women of various ages and impacts all aspects of life. Objective: Our objective was to assess the efficacy and safety of vaginal Fractional CO2laser treatment for mild-to-severe stages of female stress UI (SUI).Materials and Methods: A total of 60 women with a mean age of 47.6 ± 8 years suffering from SUI were included in this prospective, single-center, nonrandomized, pilot study. Patients were clinically examined and assessed before treatment and at each follow-up visit at 1, 3, and 6 months postvaginal fractional CO2laser treatment by International Consultation on Incontinence Questionnaire-UI Short Form (ICIQ-UI SF) questionnaire for assessing the degree of incontinence and its impact on the quality of life, Pelvic Organ Prolapse/UI Sexual Questionnaire (PISQ-12) for assessing the quality of life in the area of sexuality, digital assessment of muscle strength, and Q-tip test for evaluating the mobility of the urethra and bladder neck. Two or three sessions of vaginal fractional CO2laser treatment were performed for each woman using SmartXide2 with V2LR laser. Pain during the treatment was measured at every session with a visual analog scale (VAS), any other possible adverse effect observed. Results: Significant improvement (P < 0.001) was found in ICIQ-UI scores, PISQ-12 scores, muscle strength, and Q-tip angle, at all follow-ups after treatment compared to baseline values. ICIQ-UI scores decreased at 1, 3, and 6 months follow-ups by 6.5, 7.17, and 7.30 points, respectively (P < 0.001). PISQ-12 scores increased at 1, 3, and 6 months follow-ups by 6.2, 7.8, and 9.1 points, respectively (P < 0.001). Muscle strength increased at 1, 3, and 6 months follow-ups by 1, 1.5, and 2 points, respectively (P < 0.001). Q-tip angle decreased at 1, 3, and 6 months follow-ups by 11.7°, 18.5°, and 24.2°, respectively (P < 0.001). No adverse events were reported by any patients during the procedure. Conclusion: This study demonstrated that vaginal Fractional CO2laser treatment using SmartXide2 with V2LR configuration laser system is an effective and safe treatment option for patients with mild-severe SUI

Synthesis, structure elucidation, DNA-PK, PI3K, anti-platelet and anti-bacteria activity of linear 5, 6, and 10-substituted-2-morpholino-chromen-oxazine-dione and angular 3, 4, 6-substituted-8-morpholino-chromen-oxazine-2,10-dione

<p>Coumarin, a naturally occurring or synthesised phytochemical, displays a wide range of biological activities. However, chromen-2-ones fused with 1,3-benzoxazine rings is not well documented and there is a gap in the literature which required engaging. The substituted-2-thioxo-chromen-oxazine linear compounds <b>14a</b>–<b>i</b> and angular compounds <b>16a</b>–<b>e</b> were synthesised from the reaction of hydroxy-substituted-chromene-carboxylic <b>10</b>–<b>13</b> with freshly prepared Ph₃P(SCN)₂. 2-Morpholino-substituted-chromen-oxazine-4,8-dione and 8-morpholino-substituted-chromen-oxazine-2,10-dione <b>15a</b>–<b>f</b> and <b>17</b> were synthesised from the reaction of the corresponding oxazines <b>14</b> and <b>16</b> with morpholine. PI3K activity was observed for the hydroxy-substituted-chromene-carboxylic acid of which compound <b>13b</b> showed moderate PI3Kγ (IC₅₀=5.56 μM) and PI3Kα (IC₅₀=14.7 μM) activity. Additionally, 8-morpholino-chromen-oxazine-2,10-dione <b>17a</b> showed isoform selective PI3Kδ activity with IC₅₀=5.08 μM with non-DNA-PK ≥ 100 μM. Consequently compound <b>17a</b> can be considered as a selective PI3Kδ inhibitor with non-DNA-PK at compound concentrations ≥100 μM.</p