Synthesis of Valganciclovir Hydrochloride Congeners

Abstract

Valganciclovir hydrochloride (1) is used for the treatment of cytomegalovirus (CMV) retinitis in patients with weakened immune systems. Valganciclovir hydrochloride is a hydrochloride salt of L-valyl ester of ganciclovir (2) that exists as a mixture of two diastereomers. According to the U.S. Food and Drug Administration specifications, the diastereomeric ratio of valganciclovir hydrochloride 1 should be maintained in the range 55:45 to 45:55. According to the U.S. Food and Drug Administration specifications, the diastereomeric ratio of valganciclovir hydrochloride 1 should be maintained in the range 55:45 to 45:55. During the process development of valganciclovir hydrochloride, six related substances (impurities) were observed along with the final active pharmaceutical ingredient. Among these six impurities, ganciclovir (2) and guanine (3) are the key starting materials and degraded impurities of ganciclovir, respectively. The remaining four impurities were identified as isovalganciclovir hydrochloride (4), methoxymethylguanine (5), O-acetoxy ganciclovir (6), and isovalarylganciclovir (7). The present work describes the synthesis and characterization of these four impurities.

GRAPHICAL ABSTRACT

Keywords:

• Antiviral
• CMV retinitis inhibitor
• related substances
• valganciclovir

ACKNOWLEDGMENTS

We greatly appreciate the supportive environment encouraged at Dr. Reddy's Laboratories Ltd. We are thankful to the Intellectual Property Management (IPM), NMR group of Dr. Reddy's Research Foundation and the analytical group of Integrated Product Development Organization (IPDO) for their magnanimous support.

Notes

DRL-IPD Communication No. IPDO-IPM-00231.