Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Patent
1995-08-11
1997-04-08
Hollinden, Gary E.
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
564139, 424 9451, 424 9452, C07C23746, C07C23742, C07C23516, A61K 4904
Patent
active
056189770
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new polyiodinated compounds which can be used in contrast agents for radiography.
The invention also relates to a process for the preparation of these compounds and to the contrast agents containing them.
The subject matter of the invention is thus polyiodinated compounds of formula: ##STR4## in which R.sub.1 and R.sub.2, which are identical to or different from each other, represent a group of formula: ##STR5## and R.sub.3 and R.sub.4, which are identical to or different from each other, represent a group of formula ##STR6## in which R.sub.5 and R.sub.6, and R.sub.7 and R.sub.8, which are identical to or different from each other, represent a hydrogen atom, a linear or branched C.sub.1 -C.sub.6 alkyl, a linear or branched C.sub.1 -C.sub.6 hydroxy- or polyhydroxyalkyl, optionally additionally containing one or more C.sub.1 -C.sub.6 alkoxys, especially methoxy or ethoxy, a linear or branched (C.sub.1 -C.sub.6) alkoxy(C.sub.1 -C.sub.6)alkyl or a linear or branched (C.sub.1 -C.sub.6) hydroxy- or polyhydroxyalkoxy (C.sub.1 -C.sub.6) alkyl, said substituents R.sub.1, R.sub.2 , R.sub.3 and R.sub.4 comprising in total at least ten hydroxyls.
The preferred compounds are those of general formula (I) in which: --CH.sub.2 --CH.sub.2 OH, ##STR7## R.sub.7 being as defined above. ##STR8## are those in which: R.sub.5 represents the ##STR9## and R.sub.6 is selected from --CH.sub.3, --CH.sub.2 --CH.sub.2 OH and ##STR10##
Preferred groups ##STR11## are those in which: R.sub.7 is a defined above, ##STR12## --CHOH--CH.sub.2 OH and R.sub.8 is selected from ##STR13##
The preferred compounds of the present invention are those in which: ##STR14## and R.sub.3 and R.sub.4 represent ; ##STR15## and R.sub.3 and R.sub.4 represent ##STR16## R.sub.1 and R.sub.2 represent ##STR17## and R.sub.3 and R.sub.4 represent ; ##STR18## and R.sub.3 and R.sub.4 represent ##STR19## R.sub.1 and R.sub.2 represent ##STR20## and R.sub.3 and R.sub.4 represent ##STR21## R.sub.1 and R.sub.2 represent ##STR22## and R.sub.3 and R.sub.4 represent ##STR23## R.sub.1 and R.sub.2 represent ##STR24## and R.sub.3 and R.sub.4 represent ##STR25## R.sub.1 and R.sub.2 represent ##STR26## and R.sub.3 and R.sub.4 represent ; ##STR27## and R.sub.3 and R.sub.4 represent ; ##STR28## and R.sub.3 and R.sub.4 represent 10); ##STR29## and R.sub.3 and R.sub.4 represent ) ##STR30## and R.sub.3 and R.sub.4 represent 12).
The compounds of formula (I) of the present invention can be prepared by alkylation and/or acylation reactions.
The compounds of formula (I) of the present invention can especially be prepared by a process comprising the following stages: ##STR31## X being selected from chlorine, bromine and iodine and R'.sub.1 and R'.sub.2 represent --CO.sub.2 R with R representing C.sub.1 -C.sub.6 alkyl, and R'.sub.3 and R'.sub.4 represent --NO.sub.2, so as to produce a compound of formula (IV): ##STR32## in which R'.sub.1, R'.sub.2, R'.sub.3 and R'.sub.4 are as defined above; b) amidation of --CO.sub.2 R with an amine ##STR33## R.sub.5 and R.sub.6 being as defined above; c) reduction of nitro groups to amino groups; R'.sub.8 --COCl, R'.sub.8 representing a group R.sub.8 as defined above in which hydroxyls are protected using a conventional protective group; and, either Z--R.sub.7, Z being a labile group such as Cl, Br or I and R.sub.7 being as defined above, and deprotection of protected hydroxyls; or groups with a reagent of formula Z--R.sub.7, Z being a labile group such as Cl, Br or I and R.sub.7 being as defined above.
The reaction of stage a) preferably takes place in a suitable solvent such as xylene, nitrobenzene, nitrotoluene, DMF or pyridine, in the presence of a metal catalyst such as copper according to the Ullman method (E. Fanta, Chem. Rev., 64, 613, 1964).
The reaction of stage c) is a catalytic reduction by hydrogen on palladium charcoal or on Ranney nickel or a chemical reduction.
The iodination reaction of stage d) takes place under usual conditions, such as with aqueous ICl or I.sub.2, in the presence of KI/ethylalnine at tempe
Dugast-Zrihen Maryse
Meyer Dominique
Guerbet S.A.
Hartley Michael G.
Hollinden Gary E.
LandOfFree
Polyiodinated compounds, process of preparation and contrast age does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Polyiodinated compounds, process of preparation and contrast age, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polyiodinated compounds, process of preparation and contrast age will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2398845