Antitumor aldophosphamide analogs

C - Chemistry – Metallurgy – 07 – F

Patent

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C07F 9/24 (2006.01) A61K 31/66 (2006.01) A61K 31/70 (2006.01) C07F 9/44 (2006.01) C07H 15/252 (2006.01) C07H 19/04 (2006.01) C07H 19/10 (2006.01)

Patent

CA 2050664

-50- ABSTRACT OF THE DISCLOSURE NOVEL ANTITOMOR ALDOPHOSPHAMIDE ANALOGS A compound having the structure: Image wherein R is CH3, C2H5, C3H7, t-C4H9 or C6H5; R1 is NH2, NHCH3, NHC2H5, NHC3H7, NHC4H9, NHCH2CH2Cl, NHC6H5, N(CH3)2, N(C2H5)2, N(C3H7)2, NCH3(C2H5), NCH3(C3H7), N(CH2CH2Cl)2, NHOH, NHNHCO2CH2C6H5, NHNHCO2C(CH3)3, OCH3, OC2H5, OC3H7, OC4H9, OC6H5, OC2C6H5, CH3, C2H5, C3H7, C4H9, CH2NO2 OR CH2NH2; and R2 is NHCH2Cl or N(CH2CH2Cl)2. These compounds may be used to eliminate occult leukemic clonogenic cells from bone marrow by contacting the bone marrow with a solution comprising levels of said compound sufficient to eliminate occult leukemic clonogenic cells. Analogously, tumor cells in a host or organ of a host may be eliminated by treatment of the host or host's organ with a compound of this description. Compounds of this description are stable aldophosphamide analogs activatable by the action of an esterase and a subsequent E-2 elimination reaction to form acrolein and a phosphoramidic mustard of the formula: A stable aldophosphamide analog activatable by the action of an esterase and a subsequent spontaneous E-2 -51- elimination reaction to form acrolein and a phosphoramidic mustard, said phosphoramidic mustard having the formula Image R is NH2, NHCH3, NHC2H5, NHC3H7, NHC4H9, NHCH2CH2Cl, NHC6H5, N(CH3)2, N(C2H5)2, N(C3H7)2, NCH3(C2H5), NCH3(C3H7), N(CH2CH2Cl)2, NHOH, NHNHCO2CH2C6H5, NHNHCO2C(CH3)3, OCH3, OC2H5, OC3H7, OC4H9, OC6H5, OC2C6H5, CH3, C2H5, C3H7, C4H9, CH2NO2 or CH2NH2; and R1 is NHCH2CH2Cl or N(CH2CH2Cl)2.

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