- Synthetic method of vardenafil hydrochloride impurities
-
The invention discloses a synthetic method of vardenafil hydrochloride impurities, which relates to the technical field of pharmaceutical and chemical industry. The synthetic method comprises the following steps: taking alanine (A) as a raw material to react with acetic anhydride, generating 2-acetaminopropionic acid (B), enabling the 2-acetaminopropionic acid (B) to react with ethyl oxalyl monochloride, and generating a reaction product (C); enabling 2-ethoxybenzamidine hydrochloride (D) to react with hydrazine hydrate, generating a reaction product (E), enabling the reaction product (E) to react with the reaction product (C), and generating an impurity intermediate I (F); and enabling the impurity intermediate I (F) to generate an impurity intermediate II (G) under the effect of phosphorus oxychloride; performing sulfonation reaction on the impurity intermediate II (G) to generate a reaction product (H); and dropwise adding N-ethylpiperazine into the reaction product (H) to obtain a target product (I) 4-ethoxy-3-(3,4-dihydro-5-methyl-4-oxo-7-propylimidazole[5,1-f][1,2,4]-trizone-ketone) benzenesulfonic acid. The method is low in production cost, low in requirement on reaction conditions, favorable for the industrialized production and higher in purity of target products.
- -
-
Paragraph 0034; 0048; 0056; 0064; 0072; 0080
(2018/04/01)
-
- 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.
- -
-
Page/Page column 70
(2016/04/19)
-
- Alternative method for the synthesis of imidazo[5,1-f][1,2,4]triazin-4(3H)- one - A substrate for the preparation of phosphodiesterase (5) inhibitors
-
Imidazo[5,1-f][1,2,4]triazin-4(3H)-ones, as isosteres of purine, are of interest for pharmaceutical research as potential substrates for the synthesis of cGMP-PDE5 inhibitors. We present a novel, alternative method for the synthesis of imidazotriazinones, that differs from the previously reported ones with respect to the method of construction of the triazinone ring in the molecule. The key step in our approach is condensation of an appropriate α-keto-ester with amidrazones, leading to the triazinone heterocycle. Several different substituted imidazolotriazinones have been synthesized in this manner.
- Olszewska, Teresa,Gajewska, Ewa P.,Milewska, Maria J.
-
p. 474 - 480
(2013/02/23)
-
- 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)
-
- Imidazo[5,1-f][1,2,4]triazin-4(3H)-ones, a new class of potent PDE 5 inhibitors
-
2-Aryl-substituted imidazo[5,1-f][1,2,4]triazin-4(3H)-ones represent a new class of potent cGMP-PDE 5 inhibitors that prove to be superior to other purine-isosteric inhibitors. Subnanomolar inhibitors of PDE 5 with activity in in vivo models for erectile dysfunction have been identified. BAY 38-9456 (Vardenafil-hydrochloride) has been selected for clinical studies in the indication of erectile dysfunction.
- Haning, Helmut,Niew?hner, Ulrich,Schenke, Thomas,Es-Sayed, Mazen,Schmidt, Gunter,Lampe, Thomas,Bischoff, Erwin
-
p. 865 - 868
(2007/10/03)
-