269402-54-2

Upstream product

• 17981-81-6 chlorambucil chloride 
• 109-55-7 1-amino-3-(dimethylamino)propane 
• 305-03-3 chlorambucil 
• 5600-63-5 4-(4-nitrophenyl)butanoyl chloride 
• 130198-76-4 methyl 3-<4-phenyl>butyrate 
• 20637-09-6 methyl 4-(4-aminophenyl)butanoate 
• 79481-83-7 methyl 4-(4-(bis(2-chloroethyl)amino)phenyl)butanoate 
• 5600-62-4 4-(4-nitrophenyl)butanoic acid 

Relevant academic research and scientific papers

Quaternary ammonium compounds

Compounds of formula corresponding to either formula (Ia) or (Ib): wherein: M represents a molecule that can be used for the treatment or diagnosis of pathologies caused by attack on the cartilage, R1, R2and R3represent an alkyl group, or R1, R2and R3, together with the nitrogen atom carrying them, form a heterocycle, X represents a (C1-C6)alkylene chain in which one or more —CH2— groups are optionally replaced by a sulphur atom, an oxygen atom, or an —NR—, —CO—, —CO—NH—, —CO2—, —SO— or —SO2— group, n represents 0 or 1, Hal represents a halogen atom, or, R4represents an alkyl group, Hal represents a halogen atom, represents a molecule that can be used for the treatment or diagnosis of pathologies caused by attack on the cartilage, wherein the nitrogen atom may optionally be included in a saturated or unsaturated nitrogen-containing heterocyclic system, or included in a double bond; and pharmaceutical compositions thereof.

Synthesis and pharmacokinetic profile of a quaternary ammonium derivative of chlorambucil, a potential anticancer drug for the chemotherapy of chondrosarcoma

As a part of our targeting program based on the affinity of the quaternary ammonium moiety for cartilage, our objective was to develop more selective anticancer drugs towards chondrosarcoma that would concentrate in this malignant cartilaginous tissue and so improve the therapeutic index through a reduction of side effects. For this purpose we have synthesized and labeled with 14C a quaternary ammonium (QA) derivative of chlorambucil. Biological studies performed in rats showed that [14C]-CQA and [ 14C]-chlorambucil exhibited different pharmacokinetic profiles. The blood elimination of [14C]-CQA was faster than that of parent compound. [14C]-CQA was principally excreted by the fecal way. However, until 15 min after administration, levels of radioactivity were measured in cartilaginous tissues of rats given [14C]-CQA which was not the case for the rats which had received [14C]-chlorambucil. Although rates of radioactivity were quantified only during 15 min, these results prove that the functionalization of chlorambucil by a quaternary ammonium group allows the molecule to be carried selectively to cartilaginous tissues.

Synthesis and in vitro evaluation of quaternary ammonium derivatives of chlorambucil and melphalan, anticancer drugs designed for the chemotherapy of chondrosarcoma

To enhance affinity for malignant cartilaginous tumors (chondrosarcomas), quaternary ammonium (QA) conjugates of chlorambucil and melphalan were prepared by linking the QA moiety to nitrogen mustards via an amide bond. They exhibited closely similar and s