Practical synthesis of a Cathepsin S inhibitor: route identification, purification strategies, and serendipitous discovery of a crystalline salt form.
A "redox economical" strategy resulted in a concise, modular synthesis of compound 1, a potent Cathepsin S inhibitor. Starting from three building blocks, crude drug substance was prepared in a two-step sequence in high yield. Efficient purification of the crude drug substance was accomplished via the formation of an unusual monoethyl oxalate salt.
Johnson & Johnson Pharmaceutical Research & Development LLC, 3210 Merryfield Row, San Diego, California 92121, USA. xdeng@its.jnj.com
Xiaohu
X
Deng
Jimmy T
JT
Liang
Matthew
M
Peterson
Raymond
R
Rynberg
Eugene
E
Cheung
Neelakandha S
NS
Mani
D002403:Cathepsins / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D015195:Drug Design; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*
D011480:Protease Inhibitors; D002403:Cathepsins; C028217:cathepsin S