Synthesis of propranolol mustard as a possible lung-specific antitumor agent.
A nitrogen mustard analog of propranolol was synthesized as a potential lung-specific antitumor agent. Since dl-propranolol concentrates in lung tissue and beta-blocking activity resides only with the l-enantiomer, the d-modification could serve as a lung-directed carrier for a cytotoxic group. Reaction of 1-(1-naphthyloxy)-3-[bis(2-hydroxyethyl)amino]-2-propanol with thionyl chloride resulted in replacement of all three hydroxyl groups with chlorine. The necessary chlorination selectivity was achieved with p-toluenesulfonyl chloride in dimethylformamide solution to provide propranolol mustard, 1-(1-naphthyloxy)-3-[bis(2-chloroethyl)amino]-2-propanol. Both the trichloro compound and propranolol mustard showed reproducible activity against P-388 leukemia. Neither compound was active against the B16 tumor or Lewis lung carcinoma.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D011433:Propranolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C023656:propranolol mustard; D011433:Propranolol