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Rose Papac, M.D.; Nicholas L. Petrakis, M.D.; Fari Amini, M.D.; David A. Wood, M.D.
JAMA. 1960;172(13):1387-1391. doi:10.1001/jama.1960.63020130004012.
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An intensive search for agents of increased therapeutic benefit in the treatment of neoplastic disease has prompted the development of newer alkylating agents. To meet the requirement of increased clinical efficacy, it is necessary that such compounds exert more selective action and fewer side-effects and have dimished toxic properties.

On the basis of animal testing numerous alkylating compounds demonstrate tumor-inhibiting properties which exceed that of mechlorethamin hydrochloride (nitrogen mustard). Clinical trials with two such agents form the basis of this report.

Mannitol mustard (Degranol), also called mannomustine (British Pharmacopeia) and with a chemical structure of 1-6-(dibetachloroethylamino)-1, 6-deoxy-D-mannitol dihydrochloride (fig. 1) was synthesized by Vargha and co-workers.1 This modification of the alkylating group was introduced with the supposition that cell membranes could be readily permeated by substances, namely the sugars, which take part in cell metabolism.

Cyclophosphamide or N-N-di (beta-chlorethyl)N' O-propylenephosphoric acid ester diamide (Cytoxan, Endoxan, [fig. 1]), synthesized by


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