89461-79-0Relevant academic research and scientific papers
An eight synthesis of an orally active antihypertensive carba-prostacyclin analog
Riefling,Radunz,Merck
, p. 5487 - 5490 (2007/10/02)
A short synthesis of carbacyclin analog 1 (code no. EMD 46 335) starting from cyclopentadiene is described, with on overall yield of better than 5%. There is a need for a prostacyclin analog that is stable both chemically and metabolically. Chemical stability can be achieved by replacing to oxygen atom of the enolether function by a carbon atom (→ carbacyclin). Metabolical stability can - for instance - be enhanced by adding a substituent to the C15 or C16 carbon atom. To proceed on this line: since PGI3 is more active than PGI2, replacement of the C16-20-n-pentyl chain by a phenyl group should furthermore result in an enhancement of activity. Replacement of the C13-14-vinyl moiety by a S-CH2-link was thought to provide compounds more convenient to synthesize. We also were interested in designing a prodrug to the active part that does not only give rise to an enhanced shelf stability but also was to facilitate purification (i.e. 5 E,Z-separation) on the last step of its synthesis. On the other hand, it had to be labil enough to readily be activated in vivo and in vitro.
