Sri International

Stanford Research Institute

Edward M Acton

George L Tong

Carol W Mosher

Kenneth J Ryan

David W Henry

Michael Tracy

Allan N Fujiwara

Herbert Stone

Michael W Lerom

Compounds of the formula ##STR1## wherein R is --COCH.sub.3, --CHOHCH.sub.3, --COCH.sub.2 OH, or --CHOHCH.sub.2 OH; hydrogen; hydroxyl; a 1 to 3 carbon alkyl; a 1 to 3 carbon .omega.-hydroxyalkyl; a 2 to 7 carbon organic acid ester or diester of --COCH.sub.2 OH, --CHOHCH.sub.2 OH, or --CHOHCH.sub.3 ; or the groups --COCH.sub.2 OH, --CHOHCH.sub.2 OH, or --CHOHCH.sub.3 having a 1 to 6 carbon alkyl or aryl ether replacement of one or more hydroxyls; or 13-ketimine derivatives of --COCH.sub.3 or --COCH.sub.2 OH;

Bridged oxygen analogs of daunorubcin and doxorubicin

Disclosed herein is a new procedure for preparing the C.1-2,4-pentadienyl derivatives of 2-deoxyhexopyranoses, as well as a new procedure for allylation of daunosamine. These methods are particularly useful for the preparation of intermediates in the synthesis of adriamycin C-glycosidic analogs which are useful anti-tumor agents. These methods provide the first enabling disclosure of methods to prepare these desired adriamycin and anthrocyclinone C-glycosidic analogs.

C-glycosidic adriamycin analogs

Compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein R is: --CO--CH.sub.3, --CHOH--CH.sub.3, --CO--CH.sub.2 OH, --CHOH--CH.sub.2 OH, hydrogen, hydroxy, 1 to 3 carbon alkyl, 1 to 3 carbon terminal hydroxyalkyl; or,

Open chain-morpholino adriamycins

A group of new daunorubicin and doxorubicin derivatives is disclosed. Included in this group are 3'-deamino-3'(3'-cyano-4'-morpholinyl doxorubicin; 3'-deamino-3'-(3'-cyano-4'-morpholinyl)-13-dihydoxorubicin; (3'-deamino-3'-(3'-cyano-4'-morpholinyl) daunorubicin; 3'-deamino-3'-(3'-cyano-4'-morpholinyl)-3-dihydrodaunorubicin; and 3'-deamino-3'-(4'-morpholinyl-5-iminodoxorubicin and derivatives thereof which have excellent activity as antitumor agents.

Analogues of morpholinyl daunorubicin and morpholinyl doxorubicin

A group of new daunorubicin and doxorubicin derivatives is disclosed. These materials have the formula ##STR1## wherein R is CO--CH.sub.3 or CHOH--CH.sub.3 in the case of daunorubicin derivatives or CO--CH.sub.2 OH or CHOH--CH.sub.2 OH in the case of doxorubicin derivatives; X is O or NH; and A is either a cyano group (CN) or a hydrogen, subject to the limitation that when X is O, A must be a cyano group. When A is hydrogen, these compounds can exist as acid addition salts, as well. Derivatives of these compounds are disclosed as well.

5-Iminodoxorubicin and its pharmaceutically acceptable acid addition salts having good antitumor activity.

5-Iminodoxorubicin

Described are 3'-deamino-3'-(4-methoxy-1-piperidinyl) derivatives of daunorubicin and doxorubicin having the formula ##STR1## wherein R is COCH.sub.3 or --CHOHCH.sub.3 in the case of daunorubicin derivatives, or is COCH.sub.2 OH or --CHOH--CH.sub.2 OH in the case of doxorubicin derivatives together with their pharmaceutically acceptable acid salts. The compounds have utility as antitumor agents.

3'-Deamino-3'-(4-methoxy-1-piperidinyl) derivatives of daunorubicin and

Described are 3'-deamino-3'-(4-morpholinyl) derivatives of daunorubicin and doxorubicin having the formula ##STR1## wherein R is COCH.sub.3 or --CHOHCH.sub.3 in the case of daunorubicin derivatives, or is --COCH.sub.2 OH or --CHOHCH.sub.2 OH in the case of doxorubicin derivatives together with their pharmaceutically acceptable acid addition salts. The compounds have utility as antitumor agents.

3-Deamino-3-(4-morpholinyl) derivatives of daunorubicin and doxorubicin

Septacidin analogs, useful as antitumor agents, having the structure ##STR1## where R is a branched or straight chain alkanoyl group of from 12 to 16 carbon atoms. A preferred compound is 6-[4,6-dideoxy-4-(isopalmitoylglycyl)-amino-.beta.-L-glucopyranosylamino]- 9H-purine.

Septacidin analogs

New compounds 4-methyl-1,4-cyclohexadiene-1-carboxaldehyde syn-oxime, 4-methoxymethyl-1,4-cyclohexadiene-1-carboxaldehyde syn-oxime, and 4-(1-methoxyethyl)-1,4-cyclohexadiene-1-carboxaldehyde syn-oxime, as well as the compound 1,4-cyclohexadiene-1-carboxaldehyde syn-oxime, are found to have a high degree of sweetness which is accompanied by very little off-taste. The compounds have good stability even in acid solution. They give no evidence of toxicity and can be employed in foods and beverages as synthetic sweetening ingredients.

1,4-Cyclohexadiene-1-carboxaldehyde syn-oxime synthetic sweetening agents

New 3-methyl-3-nitrosoureido derivatives of the following amino sugars were prepared as analogs of streptozotocin with the anomeric carbon protected, by nitrosating the methylureas in water with N.sub.2 O.sub.3 : 3-amino-3-deoxy-1,2-O-isopropylidene-.alpha.-D-ribofuranose; methyl 3-amino-3-deoxy-.beta.-D-xylopyranoside; methyl 3-amino-3-deoxy-.alpha.-D-altropyranoside; methyl 3-amino-3-deoxy-.alpha.-D-glucopyranoside; and methyl 3-amino-2,3,6-trideoxy-.alpha.-L-lyxohexopyranoside. Tests against murine leukemia L1210 show that the anticancer activity of streptozotocin not only was retained but was enhanced in most of these derivatives.

Growing community of inventors

Menlo Park, CA, United States of America

Edward M Acton