Avanafil

Base Information

• Chemical Name: Avanafil
• CAS No.: 330784-47-9
• Deprecated CAS: 330785-17-6,647841-09-6
• Molecular Formula: C23H26ClN7O3
• Molecular Weight: 483.958
• Hs Code.: 29339900
• European Community (EC) Number: 841-424-3
• UNII: DR5S136IVO
• DSSTox Substance ID: DTXSID50186727
• Nikkaji Number: J2.782.076J
• Wikipedia: Avanafil
• Wikidata: Q2873270
• NCI Thesaurus Code: C74354
• RXCUI: 1291301
• Pharos Ligand ID: KXZCSCHT87M3
• Metabolomics Workbench ID: 64826
• ChEMBL ID: CHEMBL1963681
• Mol file: 330784-47-9.mol

Synonyms:4-((3-chloro-4-methoxybenzyl)amino)-2-(2-(hydroxymethyl)-1-pyrrolidinyl)-N-(2-pyrimidinylmethyl)-5-pyrimidinecarboxamide;avanafil;stendra

Chemical Property of Avanafil

Chemical Property:

• Appearance/Colour: White solid
• Melting Point: 150-152 °C
• Refractive Index: 1.651
• PKA: 11.84±0.46(Predicted)
• PSA: 125.39000
• Density: 1.373 g/cm³
• LogP: 2.96070
• Storage Temp.: Refrigerator
• Solubility.: DMSO (Slightly), Methanol (Slightly, Heated)
• XLogP3: 2.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 9
• Exact Mass: 483.1785654
• Heavy Atom Count: 34
• Complexity: 642

Purity/Quality:

99%+ ^*data from raw suppliers

Avanafil ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: PDE5 Inhibitors
• Canonical SMILES: COC1=C(C=C(C=C1)CNC2=NC(=NC=C2C(=O)NCC3=NC=CC=N3)N4CCCC4CO)Cl
• Isomeric SMILES: COC1=C(C=C(C=C1)CNC2=NC(=NC=C2C(=O)NCC3=NC=CC=N3)N4CCC[C@H]4CO)Cl
• Recent ClinicalTrials: Daily Avanafil for Erectile Dysfunction
• Description: Avanafil (Zepeed) was approved by the Korean Health Ministry for the treatment of erectile dysfunction (ED) in August 2011. Avanafil is a highly selective type 5 phosphodiesterase (PDE5) inhibitor. Avanafil is reported to be the most selective PDE5 inhibitor on the market. The onset of Tmax and half-life also varies among the marketed PDE5 inhibitors. Sildenafil has a Tmax at 1 h and a half-life of 3–5 h. Vardenafil is somewhat similar with a Tmax of 0.6 h and a half-life of 4–6 h. Tadalafil has the longest half-life among the marketed drugs with a half-life of 17 h. Avanafil has a fast onset of action reaching Tmax in 0.6 h with a half-life of 1.2 h. A synthesis of avanafil (TA-1790) is described in the patent literature. The main elimination route of avanafil is through the bile and feces. Avanafil was also found to be reabsorbed through enterohepatic recirculation.
• Uses: Avanafil is a highly selective PDE5 inhibitor with IC50 of 1 nM. A phosphodiesterase (PDE5) inhibitor, used to treat erectile dysfunction.
• Clinical Use: Avanafil was originally discovered at Tanabe Seiyaku (now Mitsubishi Tanabe). JW Pharmaceutical (previously Choongwae Pharma) and VIVUS have since developed and launched avanafil, which is an oral PDE5 inhibitor for the treatment of erectile dysfunction (ED). Although many marketed PDE5 inhibitors (e.g. sildenafil, vardenafil and tadalafil) are available for the treatment of ED, many patients are still unable to achieve the desired results and experience undesired side-effects with these existing medications. As such, second-generation PDE5 inhibitors with enhanced PDE5 selectivity, shorter systemic half-lives, and improved tolerability are desired. Developed to meet these criteria, Avanafil exhibited good oral bioavailability and PDE5 selectivity in both preclinical studies and clinical trials. Avanafil had a short onset of action (35 min) and short half-life (1.5 h).
• Drug interactions: Potentially hazardous interactions with other drugs Alpha-blockers: enhanced hypotensive effect - maximum dose 50 mg. Antibacterials: concentration possibly increased by clarithromycin and telithromycin - avoid; concentration increased by erythromycin - reduce avanafil dose; concentration reduced by rifampicin - avoid. Antifungals: concentration increased by ketoconazole - avoid and fluconazole - reduce avanafil dose; concentration possibly increased by itraconazole and voriconazole - avoid. Antivirals: concentration possibly increased by atazanavir, indinavir and saquinavir - avoid; concentration possibly reduced by efavirenz - avoid; concentration possibly increased by fosamprenavir - reduce avanafil dose; concentration significantly increased by ritonavir - avoid. Aprepitant: concentration possibly increased by aprepitant - reduce avanafil dose. Calcium channel blockers: concentration possibly increased by diltiazem and verapamil - reduce avanafil dose. Cobicistat: concentration of avanafil possibly increased - avoid. Nicorandil: possibly enhanced hypotensive effect - avoid. Nitrates: enhanced hypotensive effect - avoid. Riociguat: possibly enhanced hypotensive effect - avoid.

Technology Process of Avanafil

There total 54 articles about Avanafil which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.0%

4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid (330785-84-7) + 2-aminomethylpyrimidine (75985-45-4) → avanafil (330784-47-9)

Guidance literature:

With dicyclohexyl-carbodiimide; 1-hydroxy-1,2,3-benzotriazine-4(3H)-one; In N,N-dimethyl-formamide; at 0 ℃; Temperature;

Reference yield: 97.2%

2-chloro-4-((3-chloro-4-methoxybenzyl)amino)-N-[pyrimidin-2ylmethyl]pyrimidine-5-carboxamide + (S)-1-Pyrrolidin-2-yl-methanol (23356-96-9) → avanafil (330784-47-9)

Guidance literature:

With triethylamine; In tetrahydrofuran; at 20 ℃; for 20h;

Reference yield: 97.0%

4-((3-chloro-4-methoxybenzyl)amino)-2-(methylthio)-N-(pyrimidin-2-ylmethyl)pyrimidine-5-formamide + (S)-1-Pyrrolidin-2-yl-methanol (23356-96-9) → avanafil (330784-47-9)

Guidance literature:

With 1H-imidazole; In toluene; at 20 ℃; for 18h; Solvent; Reagent/catalyst;

upstream raw materials:

4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid

2-aminomethylpyrimidine

4-[(3-chloro-4-methoxybenzyl)amino]-2-(methylsulfanyl)pyrimidine-5-carboxylic acid

4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester

Downstream raw materials:

(S)-2-(2-hydroxymethyl-1-pyrrolidinyl)-4-(3-chloro-4-hydroxybenzylamino)-5-[N-(2-pyrimidylmethyl)carbamoyl]pyrimidine

Refernces

• 1、 -. "Preparation method of Stendra". Paragraph 0032-0058. . Retrieved 2019/06/07.
• 2、 -. "Preparation method of pharmaceutical compound avanafil". Paragraph 0014; 0027; 0036; 0037; 0049; 0060. . Retrieved 2019/02/10.