Synthesis of 2 C-14 labeled cathepsin C inhibitors: The use of a cyanide to displace a Benzotriazole.
In support of the development of a new treatment for COPD, 2 C-14 labeled compounds were required for in vitro animal studies. The synthesis of nitrile [14C]-1 was completed in 3 steps from C-14 labeled 4-bromobenzonitrile in accord with the previously developed medicinal chemistry route. The second compound, 2, did not possess an arylnitrile as did 1, which made the synthetic design more complex. An advanced, unlabeled benzotriazole containing intermediate, 10, was synthesized in low yield over 3 steps and was subsequently reacted with K14CN to give a mixture of diastereomers 12. Separation of the diastereomers followed by deprotection afforded [14C]-2 in a 13% radiochemical yield.
Isotope Chemistry, Pharmaceutical Sciences iMED, AstraZeneca Pharmaceuticals AB, Mölndal, Sweden.
Lee
L
Kingston
Isotope Chemistry, Pharmaceutical Sciences iMED, AstraZeneca Pharmaceuticals AB, Mölndal, Sweden.
Jonas
J
Bergare
Medicinal Chemistry, Respiratory, Inflammation, and Autoimmune iMED, AstraZeneca Pharmaceuticals AB, Mölndal, Sweden.
Hans
H
Lönn
Isotope Chemistry, Pharmaceutical Sciences iMED, AstraZeneca Pharmaceuticals AB, Mölndal, Sweden.
Cecilia
C
Ericsson
Medicinal Chemistry, Respiratory, Inflammation, and Autoimmune iMED, AstraZeneca Pharmaceuticals AB, Mölndal, Sweden.
Gunnar
G
Grönberg
Pharmaron Beijing Co., Ltd., Beijing, China.
Song
S
Chen
Isotope Chemistry, Pharmaceutical Sciences iMED, AstraZeneca Pharmaceuticals AB, Mölndal, Sweden.
Charles S
0000-0001-7434-8307
CS
Elmore
D002250:Carbon Radioisotopes / Q000737:chemistry*; D020789:Cathepsin C / Q000037:antagonists & inhibitors*; D060326:Chemistry Techniques, Synthetic; D003486:Cyanides / Q000737:chemistry*; D007553:Isotope Labeling; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D014230:Triazoles / Q000737:chemistry*
D002250:Carbon Radioisotopes; D003486:Cyanides; D011480:Protease Inhibitors; D014230:Triazoles; C012771:benzotriazole; D020789:Cathepsin C
Cathepsin C Inhibitor; K14CN; benzotriazole; chiral separation