l‑Cystine Diamides as l‑Cystine Crystallization Inhibitors for Cystinuria

l-Cystine bismorpholide (1a) and l-cystine
bis­(N′-methylpiperazide) (1b)
were seven and twenty-four times more effective than l-cystine
dimethyl ester (CDME) in increasing the metastable
supersaturation range of l-cystine, respectively, effectively
inhibiting l-cystine crystallization. This behavior can be
attributed to inhibition of crystal growth at microscopic length scale,
as revealed by atomic force microscopy. Both 1a and 1b are more stable than CDME, and 1b was effective
in vivo in a knockout mouse model of cystinuria.