RESUMEN
Previous studies have suggested that an extremely strong desire for happiness might ironically reduce a person's well-being, particularly among Western people. According to the goal progress theory and the theory of valuing happiness, rumination might explain the relationship between valuing happiness and well-being. Based on these theoretical rationales, this study examined the following hypotheses: (1) valuing happiness is significantly associated with rumination, (2) people who experience low life stress have a stronger association between valuing happiness and rumination, and (3) people with more interdependent self-construal have a weaker association between valuing happiness and rumination. University students in Japan participated in a cross-sectional study (N = 350; Study 1) and a 4-weeks longitudinal study (N = 329; Study 2). They responded to a packet of questionnaires assessing valuing happiness, trait rumination, depressive symptoms, negative events, and interdependent self-construal. Consistent with our hypothesis, valuing happiness was concurrently and longitudinally associated with increased rumination after controlling for depressive symptoms. However, negative events did not moderate the association between valuing happiness and rumination. Furthermore, Study 1, but not Study 2, indicated that the association between valuing happiness and rumination was stronger among students with highly interdependent self-construal than those with less interdependent self-construal. The preset findings indicated that valuing happiness might be a factor that perpetuates rumination. More sophisticated evidence on the influence of valuing happiness on rumination can lead to effective psychotherapies for decreasing rumination and depression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04131-6.
RESUMEN
A series of (4beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented.
Asunto(s)
Glucemia/efectos de los fármacos , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Pirrolidinas/síntesis química , Animales , Inhibidores de la Dipeptidil-Peptidasa IV/síntesis química , Diseño de Fármacos , Prueba de Tolerancia a la Glucosa , Nitrilos , Pirrolidinas/farmacología , Ratas , Relación Estructura-ActividadRESUMEN
Details of structure-activity relationships (SAR) for P2 moiety of a P1 2-cyanopyrrolidine dipeptidyl peptidase IV (DPP-IV) inhibitor 4a including stereochemistry are presented. Based on this information, a series of P1 (N-alkyl)aminoacetonitrile analogs 9-20 possessing optimal P2 structure were synthesized and evaluated as inhibitors of DPP-IV. Among them, a representative compound 11, N-(cyanomethyl)-N-ethyl-L-prolinamide, was further evaluated to determine its effect on the plasma glucose level. Also 4a, 10, and 11 were evaluated for their isozyme selectivity to predict their safety problems.
Asunto(s)
Inhibidores de la Dipeptidil-Peptidasa IV , Prolina/análogos & derivados , Glucemia/efectos de los fármacos , Dipeptidil Peptidasa 4 , Inhibidores Enzimáticos/química , Humanos , Prolina/química , Prolina/farmacología , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
A series of 5beta-methylprolyl-2-cyanopyrrolidine analogs were synthesized and evaluated as DPP-IV inhibitors, and the duration of their ex vivo activity was assessed. Comparison of their potency and duration of action was done among three different species. The mode of binding was investigated, and the effect on the plasma glucose level was evaluated. Structure-activity relationships are also presented.
Asunto(s)
Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores de Proteasas/síntesis química , Inhibidores de Proteasas/farmacología , Pirrolidinas/síntesis química , Pirrolidinas/farmacología , Animales , Cromatografía en Capa Delgada , Dipeptidil Peptidasa 4/sangre , Perros , Prueba de Tolerancia a la Glucosa , Humanos , Indicadores y Reactivos , Macaca fascicularis , Espectroscopía de Resonancia Magnética , Masculino , Oxidación-Reducción , Ratas , Ratas Sprague-DawleyRESUMEN
A convergent synthesis of the E'FGH ring fragment 28 of ciguatoxin 1B, a principal toxin causing widespread seafood poisonings "ciguatera", has been accomplished through (i) coupling between the E' ring-acetylide 9 and the H ring-aldehyde 20, (ii) stereoselective F ring cyclization via an acetylene cobalt complex, (iii) conversion to a carbonyl function under high-pressure hydrogenation, and (iv) reductive hydroxyketone cyclization to construct the G ring. In the (1)H NMR analysis of 28 at room temperature, a considerable broadening phenomenon was observed due to the slow conformational changes of the FG ring, as reported for natural ciguatoxin 1B. When measured in pyridine at -20 degrees C, the spectra of 28 exhibited a 3.5:1 mixture of two conformational isomers (UP and DOWN conformers).
RESUMEN
[reaction: see text] A convergent synthesis of the E'FGH' ring fragment of ciguatoxin has been accomplished through (i) coupling between the E' ring-acetylide and the H' ring-aldehyde, (ii) stereoselective F ring cyclization via an acetylene cobalt complex, (iii) conversion to a carbonyl function, and (iv) reductive hydroxy-ketone cyclization to construct the G ring.