351863-99-5

Upstream product

• 536-74-3 phenylacetylene 
• 17733-79-8 (E)-5-phenyl-penta-2-ene-4-yne-1-ol 
• 222555-06-8 ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate 
• 117552-48-4 E-5-phenyl-pent-2-en-4-ynoic acid ethyl ester 
• 2579-22-8 Phenylpropargyl aldehyde 
• 6142-95-6 phenylpropargyl aldehyde diethyl acetal 
• 64907-51-3 (E)-(5-chloropent-3-en-1-yn-1-yl)benzene 

Relevant academic research and scientific papers

Process development and scale-up of the PPAR agonist NNC 61-4655

A scalable synthetic route of the nonselective but PPARα-preferring potent PPAR agonist NNC 61-4655 aimed for treatment of type 2 diabetes was developed. The synthetic pathway comprises the convergent synthesis and coupling of the two key intermediates E-5-(chloropent-3-en-1-ynyl)benzene 8 (prepared in a five-step synthesis in 18% overall yield) and (S)-2-ethoxy-3-(4- hydroxyphenyl)propanoic acid isopropyl ester 9. The 2-aminoethanol salt of NNC 61-4655 was selected in a preclinical salt selection program as the appropriate salt form for further development. More than 900 g of NNC 61-4655, 2-aminoethanol was finally synthesized under GMP in 98.7% purity. In comparison to the original medicinal chemistry route, starting from phenylpropargyl aldehyde 1, the overall yield towards NNC 61-4655 could be enhanced from 24 to 37%. An improved scalable two-step synthesis for 8 was developed on a laboratory scale (≥33-35% overall yield) shortly after the GMP batch.

New compounds, their preparation and use

The present invention relates to compounds of formula (I) The compounds are useful in the treatment and/or prevention of conditions mediated by nuclear receptors, in particular the Peroxisome Proliferator-Activated Receptors (PPAR).