The invention provides methods and compositions for preparing antibodies and antibody derivatives with reduced core fucosylation.

Methods and compositions for making antibodies and antibody derivatives with reduced core fucosylation

The present invention is a compound having structure (I) where: anthracycline is doxorubicin, daunorubicin or a derivative thereof; N is the 3' nitrogen of daunosamine; Ra is H or alkyl; X is O, S, CRc2 or NRc where Rc is H or alkyl; Rb is alkyl or aryl; n is 1 to 6; and m is 0 to 6. R?a and Rc? are preferably H, methyl, ethyl, propyl or butyl, although other alkyl substituents are usable. Rb is alkyl or aryl. The compound of the present invention as described above is activatable in vivo by esterases and spontaneous dehydration to form an aldehyde. The aldehyde may couple to nucleophiles of intracellular macromolecules. The compounds of the present invention are cytotoxically effective in the inhibition of human myeloma cells.

Anthracycline analogues bearing latent alkylating substituents

This invention pertains to perfluoropolyethers and perhalogenated chlorofluoroether polymers that can be prepared by fluorinating polymers made by the polymerization of acetals, ketals, polyacetals, polyketals and orthoesters with elemental fluorine.

Fluorination of acetals, ketals and orthoesters

The invention relates to new anthracycline derivatives having cytostatic activity and the general formula I, which can optionally also be in the form of an acid addition salt of physiologically acceptable inorganic or organic acids, where R1 is hydrogen or a hydroxyl group, R2 is hydrogen, a hydroxyl or a methoxy group, R3 is hydrogen or a hydroxyl group, R4 is hydrogen or a hydroxyl group, R5 is hydrogen, a hydroxyl or a methoxycarbonyl group, R6 is CH2CH3, COCH3, COCH2OH, CHOHCH3 or CHOHCH2OH and R7 is an organic substituent which has 2 to 6 carbon atoms and which contains at least one oxygen, nitrogen or sulfur atom or a C-C double bond or a C-C triple bond, it being possible for the double bond also to be a constituent of a heteroaromatic system and for the oxygen, nitrogen or sulfur atom to be a constituent of an open-chain or heterocyclic system, to a process for the preparation thereof and to the use thereof in a pharmaceutical. (see fig. I)

Anthracycline derivatives having cytostatic activity

The invention provides methods and compositions for the inhibition of fucosylation of proteins, including antibodies, in vivo by administration of a fucose analog.

Methods of inhibition of protein fucosylation in vivo using fucose analogs

The present invention relates to new L-Fucose analogs, their method of preparation, the application of such analogs to the preparation of new glycals, anthracyclines obtained by using such glycals and utilization of such anthracyclines as drugs. The glycals are obtained from L-Fucose and/or its analogs having the formula (1') and have the formula (2), wherein R is an optionally substituted linear or branched alkyl group or an optionally substituted aryl group, whith the exception of a CH2OR group or a CH2OR3 group, R3 having the same meaning as R.

New l-fucose analogs, method of preparation, application of such analogs to the preparation of new glycals, anthracyclines obtained with said glycals and utilization of said anthracyclines as drugs

Vorliegende Erfindung betrifft neue, der nachfolgenden allgemeinen Formel entsprechende Anthracycline: This invention relates to novel, the following general formula corresponding anthracyclines: worin R' und R" gleich oder verschieden sein konen und fur ein Wasserstoffatom (wobei R' dann von R" verschieden ist) oder die Gruppe -(CH 2 ) n R 1 -(CH 2 )- m -R 2 stehen, wobei wherein R 'and R "Koenen be the same or different and are a hydrogen atom (where R' then R" is different) or the group - (CH 2) n R 1 - (CH 2) - m -R 2 are each, wherein n 1 bis 6 und n is 1 to 6 and m 0 bis 4 (naturlich unter der Bedingung, dass bei m = 0 R 2 abwesend ist) betragen und m 0 to 4 (of course with the proviso that when m is 0 R 2 = is absent) and be R, eine der folgenden Gruppen: R, one of the following groups: (im Fall m = 0) (In the case of m = 0) (im Fall m = 0, wobei R 3 und R 4 gleich oder verschieden sind und ein Wasserstoffatom oder eine gegebenenfalls substituierte Alkylgruppe darstellen) -C≡N (im Fall m = 0) (in the case of m = 0, wherein R 3 and R 4 are identical or different and represent a hydrogen atom or an optionally substituted alkyl group) -C≡N (in the case of m = 0) -S- -S -O- (vorausgesetzt, dass m von O verschieden ist) -O- (provided that m is different from O) oder or (m = 0 sowie R 3 und R 4 mit den obigen Bedeutungen) (m = 0 and R 3 and R 4 having the above meanings) und R 2 (falls m von 0 verschieden ist) ein Wasserstoffatom oder eine Alkyl-, Alkoxy- oder and R 2 (if m is different from 0) is a hydrogen atom or an alkyl, alkoxy or -Gruppe (wobei R 3 und R 4 die obigen Bedeutungen haben) bedeuten. Group (wherein R 3 and R 4 have the above meanings) mean.

Anthracyclins and medicines containing them

Daunorubicin derivatives and pharmaceutical compositions thereof

This invention relates to new anthracycline having the general formula I below: (CF DRAWING IN BOPI) wherein R 'and R "which may be identical or different, represent a hydrogen atom (in which case R 'is different from R ") or the group - (CH2) n-R1- (CH2) m-R2 wherein n is between 1 and 6, m is between 0 and 4 (with, of course, provided that if m = 0, R2 is zero). R1 represents the following groups: (CF DRAWING IN BOPI) (in this case m = 0). (CF DRAWING IN BOPI) (in this case m = 0 where R3 and R4 are identical or different represent a hydrogen atom or an alkyl group substituted or not). -C- = N (in this case, m = 0). S- O- (provided that m is equal to 0). (CF DRAWING IN BOPI) or (CF DRAWING IN BOPI) (m = 0 and R3 and R4 have the same meaning as above), and R2 represents (where m ≠ 0) a hydrogen atom or alkyl, alkoxy or (CF DRAWING iN BOPI) ( R3 and R4 having the same meaning as above). Application: Medicines with anticancer activity .

New drugs containing anthracyclines and

The present invention relates to new anthracyclines corresponding to the general formula I below: ##STR1## in which R' and R", which may be identical or different, denote a hydrogen atom (and in this case R' is different from R") or the group --(CH2)n --R1 --(CH2)m --R2 where n is between 1 and 6, m is between 0 and 4 (with the proviso, of course, that if m=0, R2 is nonexistent) R1 denotes one of the following groups: ##STR2## (in this case, m=0) ##STR3## (in this case m=0) where R3 and R4, which may be identical or different, denote a hydrogen atom or a substituted or unsubstituted alkyl group) --C.tbd.N (in this case m=0) --S-- --O--(with the proviso that m is other than 0) ##STR4## (m=0 and R3 R4 have the same meaning as above) and R2 denotes (in the case where m is other than 0) a hydrogen atom or alkyl or alkoxy groups or ##STR5## (R3 and R4 having the same meaning as above). These compounds possess cytotoxic properties for treating L1210 leukemia.

Hans Peter Kraemer

Papers

New l-fucose analogs, method of preparation, application of such analogs to the preparation of new glycals, anthracyclines obtained with said glycals and utilization of said anthracyclines as drugs

Anthracyclins and medicines containing them

Daunorubicin derivatives and pharmaceutical compositions thereof

New drugs containing anthracyclines and

Anthracyclines and drugs containing them