Apremilast

CAT#: H 205894

CAS#: 608141-41-9

Description: Apremilast, also known as CC-10004, is a thalidomide analog and is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4). Apremilast specifically inhibits PDE4 and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It has anti-inflammatory activity. Apremilast was approved by the USFDA in March 2014 for treatment of adults with active psoriatic arthritis. It is also being tested for its efficacy in treating other chronic inflammatory diseases such as ankylosing spondylitis, Behcet's disease, and rheumatoid arthritis.

img

Synthetic Routes

Apremilast - Synthetic Route 1

Apremilast route01

Synthetic reference

Syu, Jin-Fong; Gopula, Balraj; Jian, Jia-Hong; Li, Wei-Sian; Kuo, Ting-Shen; Wu, Ping-Yu; Henschke, Julian P.; Hsieh, Meng-Chi; Tsai, Ming-Kang; Wu, Hsyueh-Liang. Asymmetric Synthesis of β-Aryl β-Imido Sulfones Using Rhodium Catalysts with Chiral Diene Ligands: Synthesis of Apremilast. Organic Letters. Volume 21. Issue 12. Pages 4614-4618. Journal; Online Computer File. (2019).

Apremilast - Synthetic Route 2

Apremilast route02

Synthetic reference

Man, Hon-Wah; Schafer, Peter; Wong, Lu Min; Patterson, Rebecca T.; Corral, Laura G.; Raymon, Heather; Blease, Kate; Leisten, Jim; Shirley, Michael A.; Tang, Yang; Babusis, Darius M.; Chen, Roger; Stirling, Dave; Muller, George W. Discovery of (S)-N-{2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide (Apremilast), a Potent and Orally Active Phosphodiesterase 4 and Tumor Necrosis Factor-α Inhibitor. Journal of Medicinal Chemistry. Volume 52. Issue 6. Pages 1522-1524. Journal. (2009).

Apremilast - Synthetic Route 3

Apremilast route03

Synthetic reference

Ruchelman, Alexander L.; Connolly, Terrence J. Enantioselective synthesis of the apremilast aminosulfone using catalytic asymmetric hydrogenation. Tetrahedron: Asymmetry. Volume 26. Issue 10-11. Pages 553-559. Journal; Online Computer File. (2015).

Apremilast - Synthetic Route 4

Apremilast route04

Synthetic reference

Stavber, Gaj. A novel synthetic pathway towards apremilast. Assignee Lek Pharmaceuticals d.d., Slovenia. WO 2016202806. (2016).

Apremilast - Synthetic Route 5

Apremilast route05

Synthetic reference

Dandala, Ramesh; Jayachandra, Sureshbabu; Kaushik, Vipin Kumar; Achanta, Nageshwara Rao; Dorasala, Sivaprasad. Process for the enantiomeric resolution of apremilast intermediates. Assignee Mylan Laboratories Limited, India. WO 2016174685. (2016).

Apremilast - Synthetic Route 6

Apremilast route06

Synthetic reference

Siripragada, Mahender Rao; Panchasara, Dinesh; Patel, Ilesh; Prajapati, Bhavesh; Shah, Ankit. An improved process for the preparation of apremilast and its polymorphic forms. Assignee Alembic Pharmaceuticals Limited, India. IN 2015MU04347. (2017).