Nitrogen mustards properties

Properties. The physical properties of the mustards are summarized in Table 1. The sulfur mustards are only slightly soluble in water, whereas the nitrogen mustards are slightly soluble at neutral pH, but form water-soluble salts under acid conditions. Both sulfur and nitrogen mustards are extremely soluble in most organic solvents. 

The group Cl CH2 CH2 N< occurs in the nitrogen mustards which are powerful vesicants, e.g. CH3,N(CH2,CH2C1)2. It was decided therefore to introduce this group into the fluoroacetamide molecule in the hope of combining vesicant properties with the delayed convulsant action of the fluoroacetates. For this purpose N-2 hydroxyethylfluoroacetamide (IV) was prepared by the action of monoethanolamine on methyl fluoroacetate and was readily converted into N-2-chloroethylfluoroacetamide (V) by the action of thionyl chloride ... 

Bone marrow toxicity is the major side effect of chlorambucil. Nausea is uncommon or mUd, and hair loss does not occur. Chlorambucil shares the immunosuppressive, teratogenic, and carcinogenic properties of the nitrogen mustards. 

The formation of a quaternary axiridinium salt was proposed many years ago by MarokwakJ 1 (Eq. 41) to account for observations of the properties of AT-( -chloroethyI)piperidme Later, the reactivity of nitrogen mustards with biological systems was recognized,1 and led... 

In some instances, researchers are able to develop separate Hansch equations for both activity and toxicity of a drug. Differing parameters between the activity and toxicity QSAR equations allow researchers to optimize properties that boost desired activity and minimize toxicity. The following two QSAR equations give the activity (12.d) and toxicity (12.e) for a series of nitrogen mustard antitumor compounds (see Chapter 6). Based on these equations, is it likely that a nontoxic nitrogen mustard will be developed Explain. 

Nitrogen mustards are tertiary hw(2-chloroethyl)amines with vesicant activity (NDRC, 1946). AH are active alkylating agents. The nomenclature, chemical and physical properties of HNl, HN2, and HN3 are summarized in Tables 8.3 and 8.4. Due to their toxicity and various... 

TABLE 8.4. Physical and chemical properties of nitrogen mustards... 

Cyclophosphamide is an alkylating nitrogen mustard derivative mainly used in oncology patients (1) or in conditioning regimens for bone marrow transplantation. Its immunosuppressant properties have been used in organ transplantation and more often in chronic inflammatory disorders or autoimmune diseases. 

Once it was appreciated that the nitrogen mustards were acting as electrophilic reactants, alkylating essential cellular macromolecules, other types of chemical with similar properties were tested for their tumour inhibitory action. 

Nitrogen mustards have not been stockpiled in most countries and are not further discussed here other than to say that their chemical properties resemble those of sulfur mustard (IOM, 1993). The toxicity and environmental fate of the nitrogen mustard agents have been reviewed previously (Marrs et al., 1996 Munro et al., 1999). Based on chemical properties, the persistence of nitrogen mustards range from environmentally persistent (tris[2-chloroethyl] amine... 

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