1346434-58-9

Upstream product

• 1346434-30-7 1-(methylsulfonyl)-7-azido-2-heptanol 
• 1346434-41-0 1-(methanesulfonyl)-7-azido-2-heptyl chloroformate 
• 51207-85-3 4-amino-N,N-diethylbenzamide 

Downstream Products

• 1346434-63-6 O-[1-(methanesulfonyl)-7-azido-2-heptyl]-N-[4-(diethylcarboxamido)phenyl]-N-chloromethyl carbamate 
• 1346434-72-7 C₄₃H₅₁N₇O₁₀S 

Relevant academic research and scientific papers

Macromolecular prodrug that provides the irinotecan (CPT-11) active-metabolite SN-38 with ultralong half-life, low C max, and low glucuronide formation

We have recently reported a chemical approach for half-life extension that utilizes β-eliminative linkers to attach amine-containing drugs or prodrugs to macromolecules. The linkers release free drug or prodrug over periods ranging from a few hours to over 1 year. We adapted these linkers for use with phenol-containing drugs. Here, we prepared PEG conjugates of the irinotecan (CPT-11) active metabolite SN-38 via a phenyl ether that release the drug with predictable long half-lives. Pharmacokinetic studies in the rat indicate that, in contrast to other SN-38 prodrugs, the slowly released SN-38 shows a very low Cmax, is kept above target concentrations for extended periods, and forms very little SN-38 glucuronide (the precursor of enterotoxic SN-38). The low SN-38 glucuronide is attributed to low hepatic uptake of SN-38. These macromolecular prodrugs have unique pharmacokinetic profiles that may translate to less intestinal toxicity and interpatient variability than the SN-38 prodrugs thus far studied.

SULFONE LINKERS

Sulfone linkers which couple drugs to carriers of various types are described. These linkers permit the release of the drug over time in a controlled manner. The release occurs through beta-elimination, and does not require enzymatic cleavage. Products of

HYDROGELS WITH BIODEGRADABLE CROSSLINKING

Hydrogels that degrade under appropriate conditions of pH and temperature by virtue of crosslinking compounds that cleave through an elimination reaction are described. The hydrogels may be used for delivery of various agents, such as pharmaceuticals. Thi

CONTROLLED RELEASE FROM MACROMOLECULAR CONJUGATES

The invention relates to conjugates of macromolecular carriers and drugs comprising linkers that release the drug or a prodrug through rate-controlled beta-elimination, and methods of making and using the conjugates.