TY  - JOUR
UR  - https://doi.org/10.1016/j.tetlet.2019.151428
N2  - The synthesis of the prodrug candidate, treprostinil N-acyl methylsulfonamide 5 was accomplished from treprostinil 2 utilising protecting group strategies. A more direct synthesis for the prodrug was also achieved using a treprostinil triol precursor 12 and bromoacetyl acylmethylsulfonamide 14. The overall yield of treprostinil N-acyl sulfonamide 5 directly from the triol precursor 12 is similar to the protecting group strategies because deprotonation of the acidic proton in the bromoacetyl acylmethylsulfonamide 14 reduces electrophilicity. However, the more direct route using the treprostinil triol precursor holds greater promise as a strategy to prepare a wide range of treprostinil prodrug candidates. Treprostinil N-acyl methylsulfonamide prodrug 5 exhibited a 30-fold decrease in the potency at the human prostacyclin (IP) receptor compared to treprostinil 2 in an in vitro cyclic AMP assay.
ID  - discovery10090628
A1  - Picken, C
A1  - Laing, P
A1  - Shen, L
A1  - Clapp, LH
A1  - Brocchini, S
KW  - Prostacyclin
KW  -  Treprostinil
KW  -  Acylsulfonamide
KW  -  Prodrug
JF  - Tetrahedron Letters
AV  - public
VL  - 61
Y1  - 2020/01/30/
TI  - Synthetic routes to treprostinil N-acyl methylsulfonamide
IS  - 5
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher?s terms and conditions.
ER  -