title: Synthesis and antitumor activity of cyclophosphamide analogs. 1. Benzo annulated cyclophosphamide and related systems.
abstract: Synthesis of 2-[bis(2-chloroethyl)amino]-3,4-dihydro-2H-1,3,2-benzoxazaphosphorin 2-oxide (2), which is a benzo annulated analog of cyclophosphamide [2-bis(2-chloroethyl)aminotetrahydro-2H-1,3,2-oxazaphosphorin 2-oxide (1)], was carried out in order to test for possible increased antitumor activity relative to 1 due to the presence of an oxidatively reactive C-4 benzylic site in 2. A structural isomer of 2, 2-[bis(2-chloroethyl)amino]-1,4-dihydro-2H-3,1,2-benzoxazaphosphorin 2-oxide (3), and cognate systems 2-[bis(2-chloroethyl)amino]-1,2,3,4-tetrahydro-1,3,2-benzodiazaphosphorin 2-oxide (4) and 2-[bis(2-chloroethyl)amino]-4H-1,3,2-benzodioxaphosphorin 2-oxide (5) were also prepared for comparative purposes. In vivo antitumor evaluation in mice against L1210 lymphoid leukemia indicated no significant activity for compound 2. Compounds 3 and 4 were likewise found to be inactive and only marginal activity was exhibited by 5.
mesh_terms: D000468:Alkalies; D000818:Animals; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000097:blood / Q000138:chemical synthesis / Q000627:therapeutic use; D004355:Drug Stability; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice
chemical_list: D000468:Alkalies; D003520:Cyclophosphamide