139756-21-1Relevant articles and documents
Design, synthesis and biological evaluation of pyrazolopyrimidinone based potent and selective PDE5 inhibitors for treatment of erectile dysfunction
Reddy, G. Lakshma,Dar, Mohd. Ishaq,Hudwekar, Abhinandan D.,Mahajan, Priya,Nargotra, Amit,Baba, Adil Manzoor,Nandi, Utpal,Wazir, Priya,Singh, Gurdarshan,Vishwakarma, Ram A.,Syed, Sajad Hussain,Sawant, Sanghapal D.
, (2019)
Our previous discovery of series of pyrazolopyrimidinone based PDE5 inhibitors led to find potent leads but with low aqueous solubility and poor bioavailability, and low selectivity. Now, a new series of same pyrazolopyrimidinone scaffold is designed, synthesized and evaluated for its PDE5 inhibitory potential. In this study, some of the molecules are found more potent and selective PDE5 inhibitors in vitro than sildenafil. The studies revealed that compound 5 is 20 fold selective to PDE5 against PDE6. As PDE6 enzyme is involved in the phototransduction pathway in the retina and creates distortion problem, the selectivity for PDE5 specifically against PDE6 enzyme is preferred for any development candidate and in present study, compound 5 has been found to be devoid of this liability of selectivity issue. Moreover, compound 5 has shown excellent in vivo efficacy in conscious rabbit model, it's almost comparable to sildenafil. The preclinical pharmacology including pharmacokinetic and physicochemical parameter studies were also performed for compound 5, it was found to have good PK properties and other physicochemical parameters. The development of these selective PDE5 inhibitors can further lead to draw strategies for the novel preclinical and/or clinical candidates based on pyrazolopyrimidinone scaffold.
Improved synthesis process of sildenafil
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, (2021/06/21)
The invention discloses an improved synthesis process of sildenafil, belonging to the technical field of preparation of drug intermediates. In the process, high-concentration chlorosulfonic acid is prevented from being used as a reaction solvent and reagent, and 3-5 equivalent chlorosulfonic acid is used as a reaction reagent. Compared with the prior art, the process has the characteristics of economical performance, environmental protection, safety and the like, for example, equipment cannot be corroded, the post-treatment of reaction becomes simpler, the solvent is single and can be reused, product purity is high, and the like.
α-Keto Acids as Triggers and Partners for the Synthesis of Quinazolinones, Quinoxalinones, Benzooxazinones, and Benzothiazoles in Water
Huang, Jian,Chen, Wei,Liang, Jiazhi,Yang, Qin,Fan, Yan,Chen, Mu-Wang,Peng, Yiyuan
, p. 14866 - 14882 (2021/10/25)
A general and efficient method for the synthesis of quinazolinones, quinoxalinones, benzooxazinones, and benzothiazoles from the reactions of α-keto acids with 2-aminobenzamides, benzene-1,2-diamines, 2-aminophenols, and 2-aminobenzenethiols, respectively, is described. The reactions were conducted under catalyst-free conditions, using water as the sole solvent with no additive required, and successfully applied to the synthesis of sildenafil. More importantly, these reactions can be conducted on a mass scale, and the products can be easily purified through filtration and washing with ethanol (or crystallized).
Sulphonated graphene oxide catalyzed continuous flow synthesis of pyrazolo pyrimidinones, sildenafil and other PDE-5 inhibitors
Karra, Purushotham Reddy,Mahajan, Bhushan,Pabbaraja, Srihari,Singh, Ajay K.,Sthalam, Vinay Kumar
, p. 326 - 330 (2022/01/19)
Sulphonated graphene oxide was used for cascade condensation and cyclization reactions towards accessing substituted pyrazolo pyrimidinones. Further, sulphonation and amination reactions were integrated through continuous flow chemistry to access PDE-5 inhibitors. Herein, we report a simple continuous synthetic platform that reduce tedious manual operations and accelerate the synthesis of several potent inhibitors of phosphodiesterase type-5. The developed platform enabled us to perform one-flow multi-step, multi-operational process to synthesize the PDE-5 inhibitors such as sildenafil and its analogues in 32.3 min of the reaction time, with minimal human intervention and single solvent.
