86357-09-7

Usage

Uses

Used in Pharmaceutical Industry:
Iso Ganciclovir is used as a research compound for enzymatic phosphorylation studies of antiherpetic agents. Its presence in Ganciclovir and Valganciclovir allows researchers to investigate the metabolic pathways and pharmacological effects of these anti-viral drugs, ultimately contributing to the development of more effective treatments for herpes infections.

Upstream product

• 90661-36-2 9-(2,3-diacetoxy-1-propoxymethyl)guanine 
• 96429-68-4 (+/-)-N²-acetyl-9-<(2,3-diacetoxy-1-propoxy)methyl>guanine 
• 3056-33-5 2,9-diacetylguanine 
• 18602-85-2 2,6,9-tris(trimethylsilyl)guanine 
• 19916-73-5 2-Amino-6-benzyloxypurine 
• 1429306-11-5 C₁₆H₁₇N₅O₂ 
• 1429306-12-6 C₁₆H₁₉N₅O₄ 

Relevant academic research and scientific papers

Synthesis of valganciclovir hydrochloride congeners

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.

Anti-viral guanine compounds

9-(1,3-Dihydroxy-2-propoxymethyl)guanine and 9-(2,3-dihydroxy-1-propoxymethyl)guanine have been found to have potent anti-viral activity against herpes viruses. These compounds, their acyl derivatives, their phosphate derivatives and their pharmaceutically acceptable salts, pharmaceutical formulations containing these compounds, the treatment of DNA viral or herpes viral infections with these compounds, method of preparing these compounds, and novel intermediates useful in their preparation are all disclosed. The compounds may be prepared by reaction of the appropriate acetoxymethyl ether with diacetylguanine, followed by deprotection. The acetoxymethyl ethers may be obtained by reaction of glycerol formal with acetic anhydride in the presence of a catalyst.

Synthesis and antiherpetic activity of (S)-, (R)- and (±)-9-[(2,3-dihydroxy-1-propoxy)methyl]guanine, linear isomers of 2'-nor-2'-deoxyguanosine

Racemic 9-[2,3-dihydroxy-1-propoxy)methyl]guanine [(±)-iNDG], a new analogue of acyclovir (ACV) and a structural analogue of 2'-nor-2'-deoxyguanosine (2'NDG), was synthesized and found to inhibit the replication of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Subsequently, its optical isomers, (R)- and (S)-iNDG, were prepared from chiral intermediates. The chloromethyl ethers of 1,2-di-O-benzyl-D- and -L-glycerol were made and reacted with tris(trimethylsilyl)guanine to give the 9-alkylated guanines, which were deprotected by catalytic hydrogenolysis. Against HSV-1 and HSV-2 in cell culture, (S)-iNDG was approximately 10- to 25-fold more active than the R enantiomer and had an ED50 comparable to those for ACV and 2'NDG. The inferior activity of (R)-iNDG paralleled the poor inhibition of viral DNA polymerase by its phosphorylation products. In mice infected intraperitoneally or orofacially with HSV-1 or intravaginally with HSV-2, (S)-9-[(2,3-dihydroxy-1-propoxy)methyl]guanine [(S)-iNDG] was less efficacious than 2'NDG but comparable to or more active than ACV.