Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1991-09-09
1993-11-09
Gersh, Robert
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548413, 548518, 530331, 514 18, 514 14, C07D20734, A61K 3140
Patent
active
052603296
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to ureido derivatives of substituted pyrroles, to a process for their preparation and to a pharmacological composition containing them. The pyrrole derivatives of the invention may be regarded as derivatives of Distamycin A which is a known compound having the following formula ##STR2## Literature referring to Distamycin A includes, for example NATURE 203, 1064 (1964).
The present invention provides ureido derivatives of substituted carboxypyrroles having the following general formula (I) ##STR3## wherein
each of m and n, being the same, is an integer of 1 to 3; W is oxygen of sulphur;
each of the B groups, which are the same, is
a) a saturated or unsaturated, carbocyclic or condensed carbocyclic ring substituted by one or more acid groups;
b) a saturated or unsaturated, heteromonocyclic or heterobicyclic ring, containing one or more heteroatoms chosen from nitrogen, oxygen and sulphur, substituted by one or more acid groups;
c) a pyranyl or furanyl sugar residue substituted by one or more acid groups; or
d) a --CH.sub.2 (CHA).sub.r CH.sub.2 A group, wherein each A group, being the same or different, is an acid group and r is 0, 1 or 2; and the pharmaceutically acceptable salts thereof.
When two or more acid groups are present on a B group, as defined above under a), b) and c), they may be the same or different. Examples of acid groups according to the definition of a B group given above under a), b), c) and d) for instance may be those chosen from the group including sulfonic, sulfuric, sulfamic, sulfinic, phosphoric, phosphonic, phosphamic or carboxylic acid groups, i.e. SO.sub.3 H, SO.sub.4 H, SO.sub.3 NH.sub.2, SO.sub.2 H, PO.sub.4 H.sub.2, PO.sub.3 H.sub.2, PO.sub.3 NH.sub.3 and CO.sub.2 H.
Preferably the B groups, as defined above under a), b) and c), are substituted by 1 to 3 of such acid groups.
When B is a ring as defined above under a) it is for example phenyl or naphthyl. When B is a ring as defined above under b) it is for example tetrahydropyranyl or tetrahydrofuranyl. When B is a sugar residue as defined above under c) it is for example a residue deriving from glucose or ribose.
When B is a group as defined above under d) r is preferably 2.
As already said, the invention includes within its scope also the pharmaceutically acceptable salts of the compounds of formula (I).
Examples of pharmaceutically acceptable salts are either those with inorganic bases, such as sodium, potassium, calcium and aluminium hydroxydes, or with organic bases, such as lysine, arginine, N-methyl-glucamine, triethylamine, triethanolamine, dibenzylamine, methylbenzylamine, di-(2-ethyl-hexyl)-amine, piperidine, N-ethylpiperidine, N,N-diethylaminoethylamine, N-ethylmorpholine, .beta.-phenethylamine, N-benzyl-.beta.-phenethylamine, N-benzyl-N,N-dimethylamine and the other acceptable organic amines.
Preferred compounds according to the present invention are the compounds of formula (I), wherein
each of m and n, being the same, is 2;
W is oxygen;
each of the B groups, which are the same, is a') an unsaturated carbocyclic or condensed carbocyclic ring substituted by 1 to 3 acid groups; b') a tetrahydropyranyl or tetrahydrofuranyl ring substituted by 1 to 3 acid groups; or c') a glucosefuranosyl residue substituted by 1 to 3 acid groups; and the pharmaceutically acceptable salts thereof.
Specific examples of preferred compounds of the invention, are the followings: (N-methyl-4,2-pyrrole)carbonylamino))bis(1,3-naphthalendisulfonic acid); rrole)carbonylimino))bis(3,5-naphthalendisulfonic acid); rrole)carbonylimino))bis(2,5-naphthalendisulfonic acid); (N-methyl-4,2-pyrrole)carbonylimino))bis(2,4-naphthalendisulfonic acid); (N-methyl-4,2-pyrrole)carbonylimino))bis(1,6-naphthalendisulfonic acid); (N-methyl-4,2-pyrrole)carbonylimino))bis(2,6-naphthalendisulfonic acid); (N-methyl-4,2-pyrrole)carbonylimino))bis(3,6-naphthalendisulfonic acid); (N-methyl-4,2-pyrrole)carbonylimino))bis(1,5-naphthalendisulfonic acid); (N-methyl-4,2-pyrrole)carbonylimino))bis (1-naphthalensulfonic acid); (N-methyl-4,2-pyrrole
REFERENCES:
patent: 4912199 (1990-03-01), Lown et al.
J. Med. Chem., vol. 32, Oct. 1989, J. W. Lown et al.: "Novel linked antiviral and antitumor agents related to netropsin and distamycin: synthesis and biological evaluation", pp. 2368-2375.
Ciomei et al., Proc. Am. Assoc. Cancer Res., vol. 32 (Mar. 1991), p. 387, Abstract 2300.
Franzetti et al., S.I.C. Napoli, Oct. 20-23, 1991 (Abstract).
Mariani et al., International Symposium on Angiogenesis--St. Gallen (Switzerland), Mar. 13-15, 1991 (Abstract).
Sola et al., International Symposium on Angiogenesis--St. Gallen (Switzerland), Mar. 13-15, 1991 (Abstract).
Biasoli Giovanni
Ciomei Marina
Grandi Maria
Mongelli Nicola
Paio Alfredo
Farmitalia Carlo Erba Srl
Gersh Robert
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