923672-27-9

Basic information

• Product Name: methyl (5-benzoyl-1-((phosphonooxy)methyl)-1H-benzo[d]imidazol-2-yl)carbamate
• Synonyms: methyl (5-benzoyl-1-((phosphonooxy)methyl)-1H-benzo[d]imidazol-2-yl)carbamate
• CAS NO: 923672-27-9
• Molecular Weight: 405.304
• Mol File: 923672-27-9.mol

Chemical Properties

• CAS DataBase Reference: methyl (5-benzoyl-1-((phosphonooxy)methyl)-1H-benzo[d]imidazol-2-yl)carbamate(CAS DataBase Reference)
• NIST Chemistry Reference: methyl (5-benzoyl-1-((phosphonooxy)methyl)-1H-benzo[d]imidazol-2-yl)carbamate(923672-27-9)
• EPA Substance Registry System: methyl (5-benzoyl-1-((phosphonooxy)methyl)-1H-benzo[d]imidazol-2-yl)carbamate(923672-27-9)

Safety Data

• Hazardous Substances Data: 923672-27-9(Hazardous Substances Data)

Upstream product

• 31431-39-7 mebendazole 
• 229625-50-7 di-tert-butyl chloromethyl phosphate 

Relevant articles and documents

MEBENDAZOLE PRODRUGS WITH ENHANCED SOLUBILITY AND ORAL BIOAVAILABILITY

Prodrugs of mebendazole and methods for their use in treating a disease, disorder, or disorder, including cancer, are disclosed.

N-Substituted Prodrugs of Mebendazole Provide Improved Aqueous Solubility and Oral Bioavailability in Mice and Dogs

Mebendazole (MBZ) was developed as a broad-spectrum anthelmintic but has recently shown efficacy as an anticancer agent. The use of MBZ for cancer, however, is challenging due to its poor solubility leading to poor bioavailability. Herein, we developed a prodrug approach with various N-linked promoieties including acyloxymethyl, aminoacyloxymethyl, and substituted phosphonooxymethyl in attempt to improve these characteristics. Compound 12, containing an (((((isopropoxycarbonyl)oxy)methoxy)phosphoryl)oxy)methyl promoiety, showed a >10 000-fold improvement in aqueous solubility. When evaluated in mice, 12 displayed a 2.2-fold higher plasma AUC0-t and a 1.7-fold improvement in brain AUC0-t with a calculated oral bioavailability of 52%, as compared to 24% for MBZ-polymorph C (MBZ-C), the most bioavailable polymorph. In dogs, 12 showed a 3.8-fold higher plasma AUC0-t with oral bioavailability of 41% compared to 11% for MBZ-C. In summary, we have identified a prodrug of MBZ with better physicochemical properties and enhanced bioavailability in both mice and dog.

Highly water-soluble prodrugs of anthelmintic benzimidazole carbamates: Synthesis, pharmacodynamics, and pharmacokinetics

Highly water-soluble prodrugs 1a-g of anthelmintic benzimidazole carbamates 2a-g were synthesized. These prodrugs combine high aqueous solubility and stability with high lability in the presence of alkaline phosphatases. The veterinary utility of 1a was shown by a pharmacodynamic and pharmacokinetic study performed in swine. Comparable anthelmintic efficacy was observed with prodrug 1a or the parent fenbendazole 2a. The pharmacokinetic results showed that 2a is better absorbed when derived from 1a than when applied as such.