268203-93-6

Usage

Uses

Used in Erectile Dysfunction Treatment:
Udenafil is used as a PDE5 inhibitor for the treatment of erectile dysfunction. It increases cGMP levels, leading to smooth muscle cell relaxation and increased blood flow in the penile corpus cavernosum, resulting in a sustainable erection. Udenafil has shown significant improvement in patient satisfaction, with an overall satisfaction rate of 86% compared to only 26% in the placebo group.
Used in Pulmonary Hypertension Treatment:
In a rat model of monocrotaline-induced pulmonary hypertension, Udenafil (1 and 5 mg/kg) is used as an inhibitor to increase lung cGMP levels, attenuate the development of compensatory right ventricular hypertrophy, and reduce pulmonary arterial wall thickening.
Used in Renal Ischemia-Reperfusion Injury Treatment:
Udenafil is used to increase creatinine clearance and decrease blood urea nitrogen (BUN) and serum malondialdehyde (MDA) levels in a rat model of renal ischemia-reperfusion injury.
Used in Penile Erection Induction:
Udenafil (0.3 and 10 mg/kg) is used to induce penile erections in conscious rabbits and in rabbits with acute spinal cord injury.

Originator

Dong-A (South Korea)

Synthesis

Udenafil has a unique pharmacokinetic profile with a relatively rapid onset and sufficiently long duration (Tmax 1-1.5 hr, t1/2 11-13 hr) to make it effective for up to 24 hours. Synthesis of this racemic compound started with commercially available 2-propoxybenzoic acid (160). The free acid 160 was converted to it acyl chloride with thinoy chloride in refluxing dichloromethane, which was condensed with 4-amino-1-methyl-3- propyl-1H-pyrazole-5-carboxamide (161) with TEA and DMAP in dichloromethane to yield carboxamide 162 in 85% yield from 160. Compound 162 was sulfonated with chlorosulfonic acid to yield benzenesulfonyl chloride 163 in 67% yield, which was treated with racemic 2-(1-methylpyrrolidin- 2-yl)ethylamine (164) in dichloromethane to afford sulfonamide 165 in 80% yield. Finally, compound 165 was cyclized with tBuOK in refluxing tBuOH to give udenafil (XXII) in 81% yield.

InChI:InChI=1/C25H36N6O4S/c1-5-8-20-22-23(31(4)29-20)25(32)28-24(27-22)19-16-18(10-11-21(19)35-15-6-2)36(33,34)26-13-12-17-9-7-14-30(17)3/h10-11,16-17,26H,5-9,12-15H2,1-4H3,(H,27,28,32)

Synthetic route

nicotinic acid (59-67-6) + udenafil (268203-93-6) → udenafil-nicotinic acid salt

Conditions	Yield
In ethanol at 50℃; for 0.333333h;

Upstream product

• 374776-34-8 4-(5-chlorosulfonyl-2-n-propoxybenzamido)-1-methyl-3-n-propylpyrazole-5-carboxamide 
• 382592-28-1 2-methyl-4-{5-[2-(1-methyl-pyrrolidin-2-yl)-ethylsulfamoyl]-2-propoxy-benzoylamino}-5-propyl-2H-pyrazole-3-carboxamide 
• 139756-23-3 5-(2-n-propoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 
• 139756-04-0 1-Methyl-4-(2-n-propoxybenzamido)-3-n-propylpyrazole-5-carboxamide 
• 51387-90-7 2-(2-AMINOETHYL)-1-METHYLPYRROLIDINE 
• 139756-24-4 5-(5-chlorosulphonyl-2-n-propoxyphenyl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one 

Downstream Products

• 1240622-28-9 udenafil benzenesulfonate 
• 1240622-32-5 udenafil cyclamate 

Relevant academic research and scientific papers

Preparation method for heterocyclic compounds

The invention specifically relates to a preparation method for heterocyclic compounds with udenafil as a representative, belonging to the field of chemical pharmaceutical technology. The invention aims to overcome the technical problems of high production cost, low yield, great treatment quantities of waste acid and exhaust gas and potential safety hazards in conventional synthetic methods. To overcome the technical problems, the invention provides the preparation method for the heterocyclic compounds. The preparation method comprises the following steps: 1, subjecting a starting raw materialA to a reaction under the action of an organic solvent and alkali to produce an intermediate 1; 2, reacting the intermediate 1 with a sulfonating agent to produce an intermediate 2; and 3, reacting the intermediate 2 with a starting raw material B in an organic solvent to obtain a finished compound as shown in a formula I. The preparation method provided by the invention uses easily available andcheap raw materials, avoids usage of expensive coupling reagents, improves the selectivity of next-step sulfonation, and is high in product yield and purity, mild in reaction conditions and beneficialfor scaled-up production in workshops.

PHARMACOLOGICAL COMPOSITION FOR PREVENTION AND TREATMENT OF RESPIRATORY DISEASE CONTAINING PYRAZOLOPYRIMIDINONE COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

Disclosed herein is composition for prevention and treatment of respiratory disease containing a pyrazolopyrimidinone compound or pharmaceutically acceptable salts thereof as an active ingredient.

HIGHLY SELECTIVE and LONG-ACTING PDE5 MODULATORS

Disclosed herein are substituted phosphodiesterase type 5 enzyme modulators of Formula I, processes of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.

AGENT FOR THE PREVENTION AND TREATMENT OF LIVER DISEASES CONTAINING PYRAZOLOPYRIMIDINE DERIVATIVE

The present invention relates to the pharmaceutical compositionfor prevention and treatment of liver diseases containing pyrazolopyrimidine derivative as an active ingredient. According to the present invention, pyrazolopyrimidine derivative has an excellent effect on inhibiting collagen synthesis in hepatic stellate cellsand acts directly on the portal vein. Particularly, it may increase the diameter and the amount of blood flow of the portal vein, and finally decrease the pressure thereof. Therefore, pyrazolopyrimidine derivative can be used advantageously for prevention and treatment of hepatic fibrosis, liver cirrhosis caused by hepatic fibrosis, portal hypertension and various complications caused by portal hypertension. In addition, pyrazolopyrimidine derivative according to the present invention can reduce dosing frequency because of its long half-life, and therefore, has an advantage to improve the drug compliance of patients suffering from chronical liver diseases.