Nitrogen lost derivatives

The substance group of nitrogen lots comprises a number of chlorinated organic nitrogen-containing compounds in which 2 or 3 H-atoms of ammonia are replaced by β-chloroethyl radicals. N-lost derivatives (Lost is an abbreviation of the names of the developers Lommel and Steinkopf) are

The nitrogen-lost derivatives are chemically derived from the bis(β-chloroethyl)-sulfide (Lost) and are strongly alkylating compounds due to the participation of neighbouring groups of the N-atom. Thus they are counted among the alkylating(alkylanic) cytostatics.

Nitrogen-lost compounds include:

• cyclophosphamide
• Trofosfamide
• Ifosfamide
• Chlorambucil
• Melphalan

The reacting electrophilic centre is the C atom to which a Cl atom is bound. The reactivity of the molecule depends on the basicity of the N atom. Nitrogen-lost derivatives with aromatically substituted and therefore less basic N-atom, e.g. chlorambucil, are used as direct alkyl agents.

In many cases nitrogen-host derivatives with lower reactivity are also used as prodrugs, which act as indirect alkyl agents and in which the reactive compounds are only formed during the biotransformation process. The best-known example of a nitrogen-host prodrug is cyclophosphamide, which is only metabolised to 4-hydroxy-cyclophosphamide in the liver. 4-Hydroxy-Cyclophosphamide then reaches all organs via the bloodstream where it is converted into the alkylating agent phosphoric acid amide -Lost by splitting off acrolein. In this way, the substance causes intra- and interstrand cross-linking of the DNA and thus has a cytostatic effect.

Lost is mainly known as a chemical weapon because of the use of some of these substances. The sulphuric fumigate, often simply referred to as mustard gas, is the best known representative of this group of substances.