224789-26-8Relevant articles and documents
Vardenafil hydrochloride related substance, preparation method and applications thereof
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, (2020/03/06)
The invention provides a vardenafil hydrochloride related substance, a preparation method and applications thereof, wherein the vardenafil hydrochloride related substance has a structural formula represented by a formula I. According to the invention, the
NOVEL DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF
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Page/Page column 93-96, (2020/06/19)
The present invention relates to compounds of formula (I) or formula (II) or pharmaceutically acceptable salt, solvate or hydrate thereof, wherein said compound of formula (I) and said compound of formula II each comprises at least one ONO2 or ONO moiety; R1 is C1-C3alkyl; R2 is H, C1-C6alkyl, C3-C6cycloalkyl, C1-C2alkoxy, C2-C4alkenyl; R3 is C1-C4alkyl optionally substituted with C1-C2alkoxy, C3-C4cycloalkyl, C2-C4alkenyl; R4 and R5 are each independently H or C1-C6alkyl optionally substituted with F, OH, ONO, ONO2, COOH, C1-C3alkoxy, C3-C6cycloalkyl; or together with the nitrogen atom to which they are attached form a heterocyclic ring, wherein preferably said heterocyclic ring is selected from aziridine, azetidine, pyrollidine, piperidine, morpholine, piperazine, homo-piperazine, 2,5-diazabicyclo[2,2,1]heptane and 3,7-diazabicyclo[3,3,0]octane, wherein said heterocyclic ring is optionally substituted with independently one or more R6; R6 is C1-C6alkyl optionally substituted with independently one or more halogen, OH, ONO, ONO2, C1-C3alkoxy, C1-C3haloalkoxy, COOR7, NR8R9, C=NR10; R7 is H, or C1-C4alkyl optionally substituted with F, OH, ONO, ONO2, NR8R9; R8 and R9 are independently H, or C1-C4alkyl optionally substituted with ONO, ONO2; R10 is C1-C4alkyl optionally substituted with F, ONO, ONO2; C3-C6cycloalkyl; pharmaceutical compositions thereof, and their use in methods of treating or preventing a disease alleviated by inhibition of PDE5 in a human or in a non-human mammal.
Discovery of in Vivo Chemical Probes for Treating Alzheimer's Disease: Dual Phosphodiesterase 5 (PDE5) and Class i Histone Deacetylase Selective Inhibitors
Rabal, Obdulia,Sánchez-Arias, Juan A.,Cuadrado-Tejedor, Mar,De Miguel, Irene,Pérez-González, Marta,García-Barroso, Carolina,Ugarte, Ana,Estella-Hermoso De Mendoza, Ander,Sáez, Elena,Espelosin, Maria,Ursua, Susana,Haizhong, Tan,Wei, Wu,Musheng, Xu,Garcia-Osta, Ana,Oyarzabal, Julen
, p. 1765 - 1782 (2019/01/08)
In order to determine the contributions of histone deacetylase (HDAC) isoforms to the beneficial effects of dual phosphodiesterase 5 (PDE5) and pan-HDAC inhibitors on in vivo models of Alzheimer's disease (AD), we have designed, synthesized, and tested novel chemical probes with the desired target compound profile of PDE5 and class I HDAC selective inhibitors. Compared to previous hydroxamate-based series, these molecules exhibit longer residence times on HDACs. In this scenario, shorter or longer preincubation times may have a significant impact on the IC50 values of these compounds and therefore on their corresponding selectivity profiles on the different HDAC isoforms. On the other hand, different chemical series have been explored and, as expected, some pairwise comparisons show a clear impact of the scaffold on biological responses (e.g., 35a vs 40a). The lead identification process led to compound 29a, which shows an adequate ADME-Tox profile and in vivo target engagement (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation) in the central nervous system (CNS), suggesting that this compound represents an optimized chemical probe; thus, 29a has been assayed in a mouse model of AD (Tg2576).
Impact of Scaffold Exploration on Novel Dual-Acting Histone Deacetylases and Phosphodiesterase 5 Inhibitors for the Treatment of Alzheimer’s Disease
Sánchez-Arias, Juan A.,Rabal, Obdulia,Cuadrado-Tejedor, Mar,De Miguel, Irene,Pérez-González, Marta,Ugarte, Ana,Sáez, Elena,Espelosin, Maria,Ursua, Susana,Haizhong, Tan,Wei, Wu,Musheng, Xu,Garcia-Osta, Ana,Oyarzabal, Julen
, p. 638 - 661 (2017/03/20)
A novel systems therapeutics approach, involving simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylase (HDAC), has been validated as a potentially novel therapeutic strategy for the treatment of Alzheimer’s disease (AD). First-in-class dual inhibitors bearing a sildenafil core have been very recently reported, and the lead molecule 7 has proven this strategy in AD animal models. Because scaffolds may play a critical role in primary activities and ADME-Tox profiling as well as on intellectual property, we have explored alternative scaffolds (vardenafil- and tadalafil-based cores) and evaluated their impact on critical parameters such as primary activities, permeability, toxicity, and in vivo (pharmacokinetics and functional response in hippocampus) to identify a potential alternative lead molecule bearing a different chemotype for in vivo testing.
Preparation method for vardenafil impurities
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Paragraph 0049; 0050; 0051; 0052, (2016/12/22)
The invention relates to a preparation method for vardenafil impurities. The preparation method is of great significance to synthesis of high-quality vardenafil. The preparation method comprises the following steps: subjecting 2-(2-ethoxyphenyl)-5-methyl-
NOVEL COMPOUNDS FOR USE IN COGNITION IMPROVEMENT
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Page/Page column 51; 71, (2016/04/19)
Novel compounds for use in cognition improvement It relates to certain compounds having a polycyclic structure and a -(C=O)NRaRb moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases.
THE METHOD FOR MANUFACTURING OF VARDENAFIL AND ITS SALTS
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Page/Page column 8; 9, (2015/07/07)
The method of synthesizing vardenafil base, in anhydrous conditions, by chlorosulfonation of 2- (2-etoxy-phenyl)-5-methyl-7-propyl-iH-imidazo[5,l-fJ[l,2,4]triazin-4-one in a mixture of thionyl chloride and sulfurochloridic acid followed by amidation of th
Pyrazolopyrimidinone Compound and Imidazo Triazone Compound for Treating Erectile Dysfunction
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Paragraph 0051; 0052, (2014/02/16)
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.
NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES
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Page/Page column 82; 140, (2014/09/16)
It relates to certain compounds having a polycyclic structure and a hydroxamic acid moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to a process for their preparation, as well as to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases. wherein B1 is a radical selected from the group consisting of formula (A"), formula (B"), formula (C"), and formula (D"):
PYRAZOLOPYRIMIDINONE COMPOUND AND IMIDAZO-TRIAZONE COMPOUND FOR TREATING ERECTILE DYSFUNCTION
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Paragraph 0029; 0030, (2014/01/07)
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.