University of Texas System

Pro-neuron, Inc.

David Farquhar

Abdallah Cherif

Borje S Andersson

Yuqiang Wang

Yugiang Wang

Anthracycline analogues bearing latent alkylating substituents

The present invention is a compound having the structure

Methods of treatment with anthracycline derivatives

The present invention is a compound having the structure ##STR1##

A compound having the structure: ##STR1## wherein R is CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, t-C.sub.4 H.sub.9 or C.sub.6 H.sub.5 ; R.sup.1 is NH.sub.2, NHCH.sub.3, NHC.sub.2 H.sub.5, NHC.sub.3 H.sub.7, NHC.sub.4 H.sub.9, NHCH.sub.2 CH.sub.2 Cl, NHC.sub.6 H.sub.5, N(CH.sub.3).sub.2, N(C.sub.2 H.sub.5).sub.2, N(C.sub.3 H.sub.7).sub.2, NCH.sub.3 (C.sub.2 H.sub.5), NCH.sub.3 (C.sub.3 H.sub.7), N(CH.sub.2 CH.sub.2 Cl).sub.2, NHOH, NHNHCO.sub.2 CH.sub.2 C.sub.6 H.sub.5, NHNHCO.sub.2 C(CH.sub.3).sub.3, OCH.sub.3, OC.sub.2 H.sub.5, OC.sub.3 H.sub.7, OC.sub.4 H.sub.9, OC.sub.6 H.sub.5, OC.sub.2 C.sub.6 H.sub.5, CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, C.sub.4 H.sub.9, CH.sub.2 NO.sub.2 or CH.sub.2 NH.sub.2 ; and R.sup.2 is NHCH.sub.2 CH.sub.2 Cl or N(CH.sub.2 CH.sub.2 Cl).sub.2.

Antitumor aldophosphamide glycoside and dideoxyuridine derivatives

A compound having the structure: ##STR1## wherein R is CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, t--C.sub.4 H.sub.9 or C.sub.6 H.sub.5 ; R.sup.1 is NH.sub.2, NHCH.sub.3, NHC.sub.2 H.sub.5, NHC.sub.3 H.sub.7, NHC.sub.4 H.sub.9, NHCH.sub.2 CH.sub.2 Cl, NHC.sub.6 H.sub.5, N(CH.sub.3).sub.2, N(C.sub.2 H.sub.5).sub.2, N(C.sub.3 H.sub.7).sub.2, NCH.sub.3 (C.sub.2 H.sub.5), NCH.sub.3 (C.sub.3 H.sub.7), N(CH.sub.2 CH.sub.2 Cl).sub.2, NHOH, NHNHCO.sub.2 CH.sub.2 C.sub.6 H.sub.5, NHNHCO.sub.2 C(CH.sub.3).sub.3, OCH.sub.3, OC.sub.2 H.sub.5, OC.sub.3 H.sub.7, OC.sub.4 H.sub.9, OC.sub.6 H.sub.5, OC.sub.2 C.sub.6 H.sub.5, CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, C.sub.4 H.sub.9, CH.sub.2 NO.sub.2 or CH.sub.2 NH.sub.2 ; and R.sup.2 is NHCH.sub.2 CH.sub.2 Cl or N(CH.sub.2 CH.sub.2 Cl).sub.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 elimination reaction to form acrolein and a phosphoramidic mustard, said phosphoramidic mustard having the formula ##STR2## R is NH.sub.2, NHCH.sub.3, NHC.sub.2 H.sub.5, NHC.sub.3 H.sub.7, NHC.sub.4 H.sub.9, NHCH.sub.2 CH.sub.2 Cl, NHC.sub.6 H.sub.5, N(CH.sub.3).sub.2, N(C.sub.2 H.sub.5).sub.2, N(C.sub.3 H.sub.7 (.sub.2, NCH.sub.3 (C.sub.2 H.sub.5), NCH.sub.3 (C.sub.3 H.sub.7), N(CH.sub.2 CH.sub.2 Cl).sub.2, NHOH, NHNHCO.sub.2 CH.sub.2 C.sub.6 H.sub.5, NHNHCO.sub.2 C(CH.sub.3).sub.3, OCH.sub.3, OC.sub.2 H.sub.5, OC.sub.3 H.sub.7, OC.sub.4 H.sub.9, OC.sub.6 H.sub.5, OC.sub.2 C.sub.6 H.sub.5, CH.sub.3, C.sub.2 H.sub.5, C.sub.3 H.sub.7, C.sub.4 H.sub.9, CH.sub.2 NO.sub.2 or CH.sub.2 NH.sub.2 ; and R.sup.1 is NHCH.sub.2 CH.sub.2 Cl or N(CH.sub.2 CH.sub.2 Cl).sub.2.

Novel antitumor aldophosphamide analogs

A method for purging tumor cells from bone marrow of a host, the method comprising

Selective elimination of malignant cells from bone marrow by bis

Protective groups are provided which are suitable for masking phosphates and phosphonates. The protected compositions can be introduced in a biological system and then demasked under certain biological conditions. This method permits phosphates and phosphonates which would themselves degrade in the biological system and therefore be ineffective to be introduced in a protected form and late released under the proper conditions.

Biologically reversible phosphate and phosphonate protective gruops

A compound having the structure ##STR1## wherein R is CH.sub.3 or C.sub.2 H.sub.5 1; R.sup.1 is NH.sub.2, NHCH.sub.3, NHC.sub.2 H.sub.5, NHC.sub.2 H.sub.4 Cl, N(CH.sub.3).sub.2, N(C.sub.2 H.sub.5).sub.2, N(C.sub.2 H.sub.4 Cl).sub.2, OCH.sub.3, C.sub.2 H.sub.5, CH.sub.3, or C.sub.2 H.sub.5, and R.sup.2 is N(C.sub.2 H.sub.4 Cl).sub.2 or NH C.sub.2 H.sub.4 Cl. 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: ##STR2## wherein R is NH.sub.2, NHCH.sub.3, NHC.sub.2 H.sub.5, NHC.sub.2 H.sub.4 Cl, N(CH.sub.3).sub.2, N(C.sub.2 H.sub.5, N(C.sub.2 H.sub.4 Cl).sub.2, OCH.sub.3, OC.sub.2 H.sub.5, CH.sub.3 or C.sub.2 H.sub.5.

Growing community of inventors

Houston, TX, United States of America

David Farquhar