cas 224789-26-8, 4-Ethoxy-3-(5-methyl-4-oxo-7-propyl-3,4-dihydro-imidazo[5,1-f][1,2,4]-triazin-2-yl)benzene-sulfonyl Chloride

Articles about 224789-26-8Total 16 be found

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Vardenafil hydrochloride related substance, preparation method and applications thereof
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
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(2020/03/06)

NOVEL DUAL MODE OF ACTION SOLUBLE GUANYLATE CYCLASE ACTIVATORS AND PHOSPHODIESTERASE INHIBITORS AND USES THEREOF
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.
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Page/Page column 93-96

(2020/06/19)

Discovery of in Vivo Chemical Probes for Treating Alzheimer's Disease: Dual Phosphodiesterase 5 (PDE5) and Class i Histone Deacetylase Selective Inhibitors
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).
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)

Impact of Scaffold Exploration on Novel Dual-Acting Histone Deacetylases and Phosphodiesterase 5 Inhibitors for the Treatment of Alzheimer’s Disease
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.
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)

Preparation method for vardenafil impurities
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-
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Paragraph 0049; 0050; 0051; 0052

(2016/12/22)

NOVEL COMPOUNDS FOR USE IN COGNITION IMPROVEMENT
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.
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Page/Page column 51; 71

(2016/04/19)

THE METHOD FOR MANUFACTURING OF VARDENAFIL AND ITS SALTS
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
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Page/Page column 8; 9

(2015/07/07)

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.
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Paragraph 0051; 0052

(2014/02/16)

NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES
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"):
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Page/Page column 82; 140

(2014/09/16)

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.
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Paragraph 0029; 0030

(2014/01/07)

A METHOD FOR THE PREPARATION AND ISOLATION OF SALTS OF VARDENAFIL WITH ACIDS
The subject of this invention provides a method of preparation and isolation of water-insoluble or partially soluble salts of vardenafil of formula 1, in particular its salts with acids in the ratio of components 1 : 1 (of formula 2a, HA stands for any acid), and of crystalline hydrates of said salts. These solid forms, in particular crystalline vardenafil hydrochloride trihydrate of formula 4, can be directly, without additional purification, used in preparation of a medicine for the therapy of erectile dysfunction. The present solution is based on using water as a suitable medium both for obtaining of extracts of the water-soluble forms of vardenafil, and for isolation and subsequent crystallization of solid water-insoluble or partially soluble salts of vardenafil with acids (1 : 1). Crystallization of the isolated salts takes place after adjustment of pH of the aqueous solutions by means of aqueous solutions of bases or acids, wherein no organic solvent or a mixture thereof with water is needed for the crystallization. The method according to this invention reduces costs for organic solvents, increases efficiency of isolation of the vardenafil salts with acids, and facilitates preparation of poorly stable hydrates of these salts.
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Page/Page column 16; 17

(2013/06/06)

Synthesis and spectral characterization of related substances of vardenafil, an erectile dysfunction drug
Vardenafil hydrochloride trihydrate (Levitra) is used to treat erectile dysfunction (ED) and is an inhibitor of phosphodiesterase type 5 (PDE-5) enzyme. It maintains higher levels of cyclic guanosine monophosphate (cGMP), relaxes smooth muscles, promotes penile blood flow, and enhances erectile function. During the bulk drug synthesis of vardenafil hydrochloride trihydrate, six related substances (impurities), vardenafil dimer, vardenafil N-oxide, vardenafil glycene, vardenafil oxopiperazine, vardenafil oxoacetic acid, and phenyl vardenafil were identified, and these are reported herein for the first time. The present work describes the synthesis and characterization of these impurities.
Reddy, Vajrala Venkata,Naga Brahmeswara Rao, Mandava Venkata,Reddy, Ghanta Mahesh,Mukkanti, Khagga,Reddy, Ganta Madhusudhan
experimental part
p. 3513 - 3523
(2012/10/18)

NEW AGENTS FOR THE TREATMENT OF THE LOW URINARY TRACT DYSFUNCTIONS
The present invention relates to novel compounds that are derivatives of 5 -phosphodiesterase inhibitors that comprise in their formula a polysulfurated group and that are useful for treating dysfunctions of low urinary tract such as incontinence, benign prostatic hyperplasia and erectile dysfunction.
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(2009/04/25)

Synthesis of [3H] vardenafil, Levitra, using a new labeling technique
Tritium was introduced into the new orally active, selective phosphodiesterase type V (PDE V) inhibitor vardenafil (Levitra), by reduction of a suitable amide precursor with freshly prepared lithium aluminum tritide. A specific activity of 52.7 Ci/mmol (1
Pleiss
p. 1241 - 1247
(2007/10/03)

2-Phenyl-substituited Imidazotriazinones as Phoshodiesterase Inhibitors
2-(Sulfamoyl-substituted phenyl)-3H-imidazo (5,1-f) (1,2,4) triazin-4-ones (I) are new. Imidazotriazinones of formula (I) and their salts, N-oxides and isomeric forms are new: R1 = H or 1-4C alkyl; R2 = 1-4C straight chain alkyl; R3, R4 = H, 2-8C alkenyl, 1-8C alkoxy or 1-10C alkyl (optionally interrupted by O and/or substituted by a very wide range of specific groups); or R3 or R4 = NR20R21, adamantyl, 2,2-dimethyl-4-phenyl-1,3-dioxan-5-yl, sulfolanyl, hydroxy-sulfolanyl, 2-oxo-tetrahydrofuran-3-yl; or 3-8C cycloalkyl, 6-10C aryl or 5-7 membered heterocycle, all optionally substituted by specific groups; or NR3R4 = (a) optionally benzo-fused, saturated, partially unsaturated or unsaturated 5-7 membered heterocycle, optionally containing 1-3 of S, N, O and NR37 and optionally substituted by a very wide range of specific groups; or (b) a group of formula (i)-(iv); R20,R21 = H or 1-6C alkyl; R37 = H, OH, CHO, CF3, up to 4C acyl, up to 4C alkoxycarbonyl, 1-4C alkoxy, 1-6C alkyl (optionally substituted by specific groups) or -(CO)iE; i = 0 or 1; E = 3-7C cycloalkyl or benzyl; 6-10C aryl or 5- or 6-membered heteroaryl, both optionally substituted by specific groups ; or 5-methyl-1-oxo-2,1,3-oxadiazol-4-yl, N-methylpiperazino or morpholino; R5,R6 = H, 1-6C alkyl, OH or 1-6C alkoxy. The full definitions are given in the DEFINITIONS (Full Definitions) field. An Independent claim is included for the preparation of (I).
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Page 45

(2010/02/05)

2-phenyl substituted imidazotriazinones as phosphodiesterase inhibitors
The 2-phenyl-substituted imidazotriazinones having short, unbranched alkyl radicals in the 9-position are prepared from the corresponding 2-phenyl-imidazotriazinones by chlorosulphonation and subsequent reaction with the amines. The compounds inhibit cGMP-metabolizing phosphodiesterases and are suitable for use as active compounds in pharmaceuticals, for the treatment of cardiovascular and cerebrovascular disorders and/or disorders of the urogenital system, in particular for the treatment of erectile dysfunction.
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(2008/06/13)