1229017-39-3

Upstream product

• 1229019-57-1 2-(2-n-Propoxyphenyl)-5,6-diethylpyrimid-4(3H)-one 
• 63874-26-0 2-n-propoxybenzamidine 
• 59643-84-4 2-n-propoxybenzamide 
• 65-45-2 salicylamide 
• 1229017-38-2 2-(5-nitro-2-n-propoxyphenyl)-5,6-diethyl-4(3H)-pyrimidone 

Downstream Products

• 1229018-86-3 2-(dimethylamino)-N-(3-(4,5-diethyl-1,6-dihydro-6-oxopyrimidin-2-yl)-4-n-propoxyphenyl)acetamide 
• 1229018-85-2 2-chloro-N-(3-(4,5-diethyl-6-oxo-1,6-dihydropyrimidin-2-yl)-4-propoxyphenyl) acetamide 

Relevant academic research and scientific papers

Facile and Cost-Effective Route for the Synthesis of Simmerafil

An improved synthesis of simmerafil, a potent PDE5 inhibitor as a clinical candidate, is described with a 38.1% overall yield and 99.7% purity. Starting from the safe and inexpensive salicylamide (15), the key intermediate 2-propoxybenzimidamide (21), which is also a potential precursor for the preparation of pyrimidinone derivatives, was effectively and conveniently obtained. The subsequent process from21to simmerafil was optimized, which makes it more amenable to scale-up.

Pharmacokinetics-Driven Optimization of 4(3 H)-Pyrimidinones as Phosphodiesterase Type 5 Inhibitors Leading to TPN171, a Clinical Candidate for the Treatment of Pulmonary Arterial Hypertension

Phosphodiesterase type 5 (PDE5) inhibitors are first-line therapy for pulmonary arterial hypertension (PAH) and erectile dysfunction. As a continuing work to improve the terminal half-lives and oral bioavailabilities of our previously reported 4(3H)-pyrimidones, a pharmacokinetics-driven optimization focusing on the terminal substituent is described. Two major congeneric series of 4(3H)-pyrimidones, the aminosulfonylphenylpyrimidones and acylaminophenylpyrimidones, were designed, synthesized, and pharmacologically assessed in vitro and in vivo. Among them, compound 15 (TPN171) with subnanomolar potency for PDE5 and good selectivity over PDE6 was finally recognized as a potential drug candidate, and its pharmacokinetic profiles in rats and dogs are significantly improved compared to the starting compound (3). Moreover, TPN171 was proven to exert a longer lasting effect than sildenafil in animal models, providing a foundation for a once-daily oral administration for its clinical use. TPN171 is currently being investigated in a phase II clinical trial for the treatment of PAH.