Cyclic phosphoramide mustard (NSC-69945) derivatives of amino acids and peptides.
The possibilities offered by a combination of the "latency" and "carrier" principles were studied by joining the phosphoramide mustard group with amino acids. The structures of the resulting derivatives are reminiscent of cyclophosphamide, but they provide feasibility for stereoisomeric modifications and for incorporation into synthetic peptides. Modlel peptides with a different ring system containing cyclic diesters of the N,N-bis(2-chloroethyl)phosphoramidic acid were also constructed. The relative intensities of antitumor activity, toxicity, and antitumor spectrum can be influenced by these molecular manipulations, indicating that the pharmacokinetics, and probably even the enzymatic activation, are markedly dependent upon the overall physiochemical properties and stereochemistry of the molecule. Another approach  has been to use larger molecular weight materials as carriers either of the phosphoramide mustard group or the cyclic amino acid derivatives. Both noncovalent and covalent linkages were tried; based on stability properties, conjugates must be regarded as more adequate potential candidates for lysosomotropism.
D000596:Amino Acids; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D007928:Lethal Dose 50; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology; D010455:Peptides; D012694:Serine; D013237:Stereoisomerism
D000596:Amino Acids; D009588:Nitrogen Mustard Compounds; D010455:Peptides; D012694:Serine; D003520:Cyclophosphamide