- 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.
- -
-
Page/Page column 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
-
p. 3513 - 3523
(2012/10/18)
-
- PROCESSES FOR THE PREPARATION OF VARDENAFIL
-
The present invention provides processes for the preparation of vardenafil, its pharmaceutically acceptable salts, hydrates and intermediates.
- -
-
-
- N-BUTYRAMIDE, THE PREPARATION METHOD AND USE THEREOF
-
Disclosed are N-{1-[3-(2-ethoxy-5-(4-ethylpiperazinyl)sulfonylphenyl)-4,5-dihydro-5-oxo-1,2,4-triazin-6-yl]ethyl}butyramide (which is represented by formula III), its preparation method, intermediates during preparation procedure, preparation method for such intermediates and a method for preparing vardenafil from the compound. In the method for preparing vardenafil, a chloro-sulfonation reaction carries out in the early stage of the preparation procedure.
- -
-
-
- A PROCESS FOR THE PREPARATION AND ISOLATION OF VARDENAFIL AND SALTS THEREOF
-
A new process for the preparation of vardenafil and isolation of its salts, in particular a citric acid salt and a crystalline form of the salt is disclosed.
- -
-
Page/Page column 11
(2011/07/30)
-
- N-{1-Y3-(2-ETHOXY-5-(4-ETHYLPIPERAZINYL)BENZENESULFONYL)-4,5-DIHYDRO-5-OXO-1,2,4-TRIAZIN-6-YL¨ETHYL}BUTYRAMIDE, THE PREPARATION METHOD AND USE THEREOF
-
Disclosed are N-{1-[3-(2-ethoxy-5-(4-ethylpiperazinyl)sulfonylphenyl)-4,5-dihydro-5-oxo-1,2,4-triazin-6-yl]ethyl}butyramide (which is represented by formula III), its preparation method, intermediates during preparation procedure, preparation method for such intermediates and a method for preparing vardenafil from the compound. In the method for preparing vardenafil, a chloro-sulfonation reaction carries out in the early stage of the preparation procedure.
- -
-
Page/Page column 9; 10
(2010/10/01)
-
- An improved synthetic route for preparative process of vardenafil
-
A new, convergent synthetic route for the process optimization of vardenafil (Levitra), a potent and effective PDE5 inhibitor, is described. Key improved steps in the preparative process are that the chlorosulfonation reaction is at the beginning and the dehydration-cyclisation reaction is at a later stage so that the synthetic route has a better overall yield and simpler workup operations. The yield of vardenafil produced from this synthetic route is around 45% over seven steps with purity at 99.2% (HPLC).
- Mao, Yongjun,Tian, Guanghui,Liu, Zheng,Shen, Jingshan,Shen, Jingkang
-
experimental part
p. 1206 - 1208
(2010/04/22)
-
- POLYMORPHIC FORMS OF VARDENAFIL
-
Crystalline polymorphic forms of vardenafil and vardenafil hydrochloride, and processes for preparing them.
- -
-
Page/Page column 6
(2010/11/28)
-
- Synergistic combinations
-
The instant invention relates to a combination of an alpha-2-delta ligand and a PDEV inhibitor for use in therapy, particularly in the curative, prophylactic or palliative treatment of pain, particularly neuropathic pain. Particularly preferred alpha-2-delta ligands are gabapentin and pregabalin. Particularly preferred PDEV inhibitors are sildenafil, vardenafil and tadalafil.
- -
-
-
- Process for the preparation of sulphonamide-substituted imidazotriazinones
-
The present invention relates to a process for the preparation of sulphonamide-substituted imidazotriazinones of the general formula (I) characterized in that compounds of the formula (II) are reacted with sulphuric acid and the products obtained are then reacted with thionyl chloride and converted in situ in an inert solvent using an amine into the compounds according to the invention and, if appropriate, reacted to give the corresponding salts, hydrates or N-oxides.
- -
-
-
- 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).
- -
-
-
- 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.
- -
-
-