- The phosphodiesterase 5 inhibitor, KJH-1002, reverses a mouse model of amnesia by activating a cGMP/cAMP response element binding protein pathway and decreasing oxidative damage
-
Background and Purpose: Inhibition of PDE5 improves synaptic plasticity and memory via enhancing cGMP expression, thus activating the cGMP/cAMP response element binding protein (CREB) signalling pathway. This study investigated the effects of a PDE5 inhibitor on scopolamine-induced cognitive dysfunction, using memory-related behavioural tests and biochemical assays. Experimental Approach: In mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine. The learning and memory abilities of mice were tested using the Morris water maze test, the Y-maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory-related bio-molecules and oxidative stress parameters in brain tissue were measured using Western blot and spectrophotometry respectively. Key Results: KJH-1002, a novel and potent inhibitor of PDE5 (IC50 0.059?±?0.04?nmol·L?1), was synthesized. In the behavioural tests, it markedly improved the memory performance impaired by scopolamine, indicating a restoration of cognitive function in the mice. Moreover, KJH-1002 increased cGMP levels in the cortex and the scopolamine-reduced expression of phosphorylated CREB, Levels of ERK 1/2, Akt and brain-derived neurotrophic factor in the cortex and hippocampus were restored by KJH-1002 treatment. In addition, KJH-1002 administration increased the activities of SOD, glutathione peroxidase and glutathione reductase, and decreased the level of malondialdehyde. Conclusion and Implications: KJH-1002 restored cognitive function in scopolamine-induced amnesia mice by activating the cGMP/CREB signalling pathway and attenuating oxidative stress. The beneficial effects of KJH-1002 on cognition indicate its potential as a therapeutic candidate for Alzheimer's disease.
- Zhang, Lijun,Seo, Jae Hong,Li, Huan,Nam, Ghilsoo,Yang, Hyun Ok
-
p. 3347 - 3360
(2018/07/31)
-
- Pyrazolopyrimidinone Compound and Imidazo Triazone Compound for Treating Erectile Dysfunction
-
Disclosed are selective phosphodiesterase inhibitor compounds shown in formula (I) or (II) for treating Erectile Dysfunction, the pharmaceutically acceptable salts and configurational isomers thereof. In the formula, the substituents R1, R2, R3, R4 and R5are defined as in the specification. Also disclosed are a medical composition comprising compounds of formula (I) or (II), and the use of these compounds for preparing a drug treating or preventing male Erectile Dysfunction.
- -
-
Paragraph 0049; 0050
(2014/02/16)
-
- PYRAZOLOPYRIMIDINONE COMPOUND AND IMIDAZO-TRIAZONE COMPOUND FOR TREATING ERECTILE DYSFUNCTION
-
Disclosed are selective phosphodiesterase inhibitor compounds shown in formula (I) or (II) for treating Erectile Dysfunction, the pharmaceutically acceptable salts and configurational isomers thereof. In the formula, the substituents R1, R2, R3, R4 and R5 are defined as in the specification. Also disclosed are a medical composition comprising compounds of formula (I) or (II), and the use of these compounds for preparing a drug treating or preventing male Erectile Dysfunction.
- -
-
Paragraph 0027; 0028
(2014/01/07)
-
- PYRAZOLOPYRIMIDINETHIONE DERIVATIVES, SALTS AND SOLVATES THEREOF, PREPARATION METHODS AND USE THEREOF
-
The present invention disclosed the pyrazolopyrimidinethione derivatives, salts and solvates thereof, preparation methods and use thereof. The pyrazolopyrimidinethione derivatives according to the present invention possess the structure of general formula I , wherein, R1, R2, R3, and R4 represent alkyl, alkenyl, or aryl; R5 represents hydrogen, alkyl, alkenyl, alkoxy, cycloalkyloxy, aryl, or alkylacyl; and R6 represents hydrogen, alkyl, alkenyl, cycloalkyloxy, or alkylacyl. The pharmaceuticals containing the compound of the present invention and used for the treatment of impotence and sexlessness have the advantages of high selectivity over PDEV, long action time, and less side reactions, and the pharmaceuticals will arouse no side reactions of blood pressure decreasing and heart rate increasing, and it has broad market propect.
- -
-
-