Apremilast

Base Information

• Chemical Name: Apremilast
• CAS No.: 608141-41-9
• Deprecated CAS: 666854-78-0
• Molecular Formula: C22H24N2O7S
• Molecular Weight: 460.508
• European Community (EC) Number: 807-237-6
• UNII: UP7QBP99PN
• ChEMBL ID: CHEMBL514800
• DSSTox Substance ID: DTXSID30976289
• Metabolomics Workbench ID: 149542
• NCI Thesaurus Code: C147044
• Nikkaji Number: J3.327.552H
• Pharos Ligand ID: GTQW8KGMM25B
• RXCUI: 1492727
• Wikidata: Q2858961
• Wikipedia: Apremilast
• Mol file: 608141-41-9.mol

Synonyms:apremilast;CC 10004;CC-10004;CC10004;Otezla

Chemical Property of Apremilast

Chemical Property:

• Boiling Point: 741.342 °C at 760 mmHg
• PKA: 14.01±0.20(Predicted)
• Flash Point: 402.149 °C
• PSA: 127.46000
• Density: 1.382 g/cm³
• LogP: 3.52590
• Storage Temp.: Refrigerator
• Solubility.: Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly, Heated)
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 8
• Exact Mass: 460.13042228
• Heavy Atom Count: 32
• Complexity: 825

Purity/Quality:

99.5%min, ^*data from raw suppliers

Apremilast ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Dermatologic Agents, Psoriasis Agents
• Canonical SMILES: CCOC1=C(C=CC(=C1)C(CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC
• Isomeric SMILES: CCOC1=C(C=CC(=C1)[C@@H](CS(=O)(=O)C)N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)C)OC
• Recent ClinicalTrials: A Study to Describe the Characteristics of Patients Treated With Apremilast for Plaque Psoriasis in Italian Routine Clinical Practice
• Recent EU Clinical Trials: A Phase 3, Multicenter, Open-label, Long-term Extension Study of Apremilast in Children 2 Years of Age or Older With Oral Ulcers Associated With Beh?et’s Disease or 5 Years of Age or Older With Juvenile Psoriatic Arthritis
• Recent NIPH Clinical Trials: A Study to Assess the Efficacy and Safety of Apremilast in Japanese Pediatric Participants With Moderate to Severe Plaque Psoriasis
• Description: Apremilast (Otezla) was approved by the FDA on March 21, 2014 for the treatment of adult patients with active psoriatic arthritis. Apremilast is a member of a new class of oral small molecule inhibitors of the phosphosphodiesterase 4 (PDE4) enzyme. When PDE4 is inhibited in immune cells, it results in elevation of intracellular cyclic adenosine monophosphate (cAMP) levels, which can regulate inflammatory mediators. The current clinical data indicate that apremilast is an effective and well tolerated option for the management of psoriasis and PsA in adults. Apremilast is the first and only oral phosphodiesterase IV (PDE- 4) inhibitor and anti-tumor necrosis factor alpha (TNFa) agent launched in the USA by Celgene for the treatment of active psoriatic arthritis (PsA). Apremilast was also approved for the treatment of moderate to severe plaque psoriasis in the USA. Later, this drug was also approved in the European Union (EU) for both indications. Although multiple approaches to the synthesis of apremilast have been described, the most likely process scale approach involves the construction of the challenging stereogenic benzylic carbon center by catalytic asymmetric hydrogenation.
• Uses: Treating active psoriatic arthritis. It is also used to treat moderate to severe plaque psoriasis in certain patients. Apremilast is an oral phosphodiesterase 4 inhibitor used in the treatment of adults with active psoriatic arthritis and adults with moderate to severe plaque psoriasis.
• Clinical Use: Treatment of active psoriatic arthritis (PsA) and moderate to severe chronic plaque psoriasis (PSOR)
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: concentration reduced by rifampicin - avoid. Antidepressants: concentration possibly reduced by St John’s wort - avoid. Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone - avoid.

Technology Process of Apremilast

There total 79 articles about Apremilast 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: 98.2%

4-amino-2-[(1S)-1-(3-ethoxy 4-methoxyphenyl)-2-methanesulfonylethyl]-2,3-dihydro-1H-isoindole-1,3-dione (635705-72-5) + acetic anhydride (108-24-7) → Apremilast (608141-41-9)

Guidance literature:

at 135 - 139 ℃; Large scale;

Reference yield: 97.0%

3-acetylaminophthalic anhydride (6296-53-3) + (S)-2-[1 (3-ethoxy-4-methoxyphenyl)]-1-methanesulfonyl-2-ethylamine (608141-42-0) → Apremilast (608141-41-9)

Guidance literature:

With acetic acid; for 1h; Reflux; Large scale;

Reference yield: 95.1%

3-acetylaminophthalic anhydride (6296-53-3) + (S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine-(S)-2-acetamido-4-methylpentanoate (608141-43-1) → Apremilast (608141-41-9)

Guidance literature:

With triethylamine; In ethyl acetate; at 75 - 80 ℃; for 18h; Reagent/catalyst; Solvent;

upstream raw materials:

3-acetylaminophthalic anhydride

(S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethanamine-(S)-2-acetamido-4-methylpentanoate

(S)-2-[1 (3-ethoxy-4-methoxyphenyl)]-1-methanesulfonyl-2-ethylamine

1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethen-1-amine

Downstream raw materials:

4-amino-2-[(1S)-1-(3-ethoxy 4-methoxyphenyl)-2-methanesulfonylethyl]-2,3-dihydro-1H-isoindole-1,3-dione

Refernces

• 1、 Vega, Kimberly B.,Cruz, Daniel M. V.,Oliveira, Artur R. T.,Da Silva, Marcos R.,De Lemos, Telma L. G.,Oliveira, Maria C. F.,Bernardo, Ricardo D. S.,De Sousa, Jackson R.,Zanatta, Geancarlo,Nasário, Fábio D.,Marsaioli, Anita J.,De Mattos, Marcos C.. "Chemoenzymatic synthesis of apremilast: A study using ketoreductases and lipases". . p. 1100 - 1110. Retrieved 2021/05/19.
• 2、 -. "METHODS FOR THE TREATMENT OF OBESITY USING APREMILAST". Paragraph 0082. . Retrieved 2019/05/22.