Efficacy and toxicity of VAC chemotherapy (vincristine, doxorubicin, and cyclophosphamide) in dogs with hemangiosarcoma.

Fifteen dogs with hemangiosarcoma were treated with a combination of vincristine, doxorubicin, and cyclophosphamide after incisional or excisional biopsy. The median survival for all fifteen dogs was 172 days (mean survival = 316 days). The median survival for those dogs with splenic hemangiosarcoma was 145 days (mean survival = 271 days) as compared with previously published median survival times in dogs with splenic hemangiosarcoma treated with surgery alone of 19 to 65 days.

4-Demethoxy-3'-N-trifluoroacetyldoxorubicin. Synthesis and solid tumor activity.

A new route has been developed for the preparation of 3'-N-protected doxorubicin analogues. 4-Demethoxy-3'-N-trifluoroacetyldoxorubicin (5) was synthesized in an approach to an orally active anthracycline analogue. Tested against the B-16 murine solid tumor in mice, this compound increased life span by 133% when it was administered intraperitoneally at 25 mg/kg, and by 52% when it was given orally at 50 mg/kg.

Mono and bis(bioreductive) alkylating agents: synthesis and antitumor activities in a B16 melanoma model.

Several potentially bis(alkylating) bis(quinones) (3-5) and 1,4- and 1,3-bis(alkylating) monoquinones (6-13) belonging to general structure 2,2'-ethylenebis[5-[(leaving group)methyl]-1,4-benzoquinone] (3-5) and 2,5- and 2,6-bis[(leaving group)methyl]-1,4-benzoquinone water-soluble and -insoluble classes were prepared by oxidative demethylation of the corresponding tetramethoxydiphenylethanes (17-19) and dimethoxybenzenes (24, 27, 36-39), respectively. Methods employed for the preparation of tetramethoxydiphenylethane intermediates involved (1) arylmethyl bromide coupling and (2) catalytic hydrogenation of stilbene intermediates derived via Wittig reaction of (arylmethyl)phosphonium salts with aryl aldehydes. However, in biological investigations using a subcutaneous B16 (hypoxic) melanoma tumor in BDF1 hybrid mice with cyclophosphamide as positive control the most interesting series of structurally related analogues were the potentially monoalkylating monoquinones of the 2-[(leaving group)methyl]-1,4-benzoquinone type (i.

Synthesis and P-388 antitumor properties of the four diastereomeric 1-hydroxy-3,4-diaminocyclohexane-Cl2PtII complexes.

Synthesis and antileukemic activity in vivo of the four diastereomeric 1-hydroxy-3,4-diaminocyclohexane-Cl2PtII complexes (Cl2PtII-3a-d) are described. Respective bis(phenylmethyl) (1 alpha,2 alpha,4 beta)-, (1 alpha,2 alpha,4 alpha)-, (1 alpha,2 beta,4 beta)-, and (1 alpha,2 beta,4 alpha)-(4-hydroxy-1,2-cyclohexanediyl)bis(carbamates) (5a, 5b, 7a, 7b) were prepared by hydroboration-oxidation of the bis(carbobenzoxyamino) derivatives (4,5) of cis- and trans-4,5-diaminocyclohexene. The relative stereochemistry of intermediates 5a and 5b was established by correlation with the alcohol obtained by NaBH4 reduction of bis(phenylmethyl) (1 alpha,2 alpha,3 alpha,4 alpha)-(3,4-epoxy-1,2-cyclohexanediyl)bis(carbamate) (8), the all-cis stereochemistry of which was unambiguously determined by X-ray crystallographic analysis.

Stereocontrolled syntheses for the six diastereomeric 1,2-dihydroxy-4,5-diaminocyclohexanes: PtII complexes and P-388 antitumor properties.

Stereocontrolled syntheses for the six diastereomeric 1,2-dihydroxy-4,5-diaminocyclohexanes 3a-f from cyclohexene diamines cis-4 and trans-5 are described. Cbz-protected species cis-9 and trans-11, respectively, served as a source of stable Cbz-protected precursors to these cyclohexanediol diamines (CDD), which were liberated upon catalytic (H2, Pd/C) hydrogenation. Catalytic osmylation of 9 afforded a mixture of diastereomeric diols 13 and 14, which served as precursors to cis-anti-cis CDD 3b and cis-syn-cis CDD 3a, respectively, whereas osmylation of 11 yielded the expected single product 12, the precursor to cis-anti-trans CDD 3d.