Alkyl compounds are largest group of anticancer drugs and they are the first compounds that used in the treatment of malignant disease. The family of phosphorylated nitrogen mustards, i.e. compounds containing the bis-(2-chloroethyl)amino group, are known to be highly effective alkylating agents with respect to a variety of nucleophilic centers, which find application in anti-tumor chemotherapy. The synthesis of phosphoramide mustards as latent alkylating agents that might be selectively activated in tumors by enzymatic (hydrolytic) release of nor-nitrogen mustard represents one of the earliest design strategies in cancer chemotherapy. Subsequently, we have synthesized a series of cyclic and noncyclic phosphoramide nitrogen mustards they have been synthesized from reaction POCl3 and bis(2-chloroethyl)amine hydrochloride then the corresponding alcohols and amines and some of their biological activities were evaluated.

In 1942, Gilman and co-workers [1] administered the nitrogen mustards 1 and 2 to a group of 9 cancer patients in the terminal phases of their disease and observed dramatic remissions of the malignancy especially in the cases of Hodgkin’s disease and lymphosarcoma. These results provided

Copyright © 2013 by Modern Scientific Press Company, Florida, USA

Int. J. Modern Org. Chem. 2013, 2(2): 171-190 172

tremendous encouragement for the use of chemotherapy, especially nitrogen mustards, for the treatment of cancer. This experiment pioneered modern cancer chemotherapy.

Today, there are many effective chemotherapeutic agents in use for cancer Chemotherapy; they fall into five broad categories including Alkylating agents, Antimetabolites[2-4], Antibiotics[5,6], Hormones, and Miscellaneous.

Among these various groups, perhaps the alkylating agents have been studied most extensively. A biological alkylating agent is defined as a compound capable of contributing an alkyl group under physiological conditions (pH 7.0-7.4, 37 oC, aqueous solution) to a component of a biological system [7]. Biological alkylating agents in clinical use can be further subdivided into four main groups including Nitrogen mustards, Ethyleneimines, Sulfonic acid esters, and Epoxides. With the great majority of alkylating agents in clinical cancer chemotherapy belonging to the group known as nitrogen mustards.