Synthesis of highly potent lymphocyte function-associated antigen-1 antagonists labeled with carbon-14 and with stable isotopes, part 3.
J Labelled Comp Radiopharm
; 62(2): 77-85, 2019 02.
Article
in En
| MEDLINE
| ID: mdl-30466143
ABSTRACT
The drug candidates (2) and (3) are highly potent LFA-1 inhibitors. They were efficiently prepared labeled with carbon-14 using a palladium-catalyzed carboxylation of an iodo-precursor (5) and sodium formate-14 C to afford acid [14 C]-(6), which was coupled via an amide bond to chiral amines (7) and (8) in 52% and 48% overall yield, respectively, and with specific activities higher than 56 mCi/mmol and radiochemical purities of 99%. For stable isotopes synthesis, the amine [2 H8 ]-(7) was synthesized in three steps from 2-cyanopyridine-2 H4 using Kulinkovich-Szymonik aminocyclopropanation, followed by coupling to L-alanine-2,3,3,3-2 H4 -N-t-BOC, and then removal of the BOC-protecting group. Amide bond formation with acid (6) gave [2 H8 ]-(2) in 36% overall yield. The amine [13 C4 ,15 N]-(8) was obtained in two steps using L-threonine-14 C4 ,15 N and then coupled to acid [13 C]-(6) to give [13 C5 ,15 N]-(3) in 56% overall yield.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carbon Radioisotopes
/
Lymphocyte Function-Associated Antigen-1
/
Radiopharmaceuticals
Type of study:
Risk_factors_studies
Language:
En
Journal:
J Labelled Comp Radiopharm
Year:
2019
Document type:
Article
Affiliation country:
United States