Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-04-04
1998-03-24
Ramsuer, Robert W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142388, 514277, 514319, 514428, 514656, 514152, 552201, A61K 31135, A61K 31495, A61K 3165
Patent
active
057313130
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP95/02928 filed Jul. 24, 1995.
The present invention relates to treating amyloidosis, to novel compounds for such treatment, to processes for their preparation and to pharmaceutical compositions containing them.
The relationship between amyloidosis, cell death and loss of tissue function appears to be of relevance for different types of disorders including neurodegenerative disorders. Therefore, the prevention of amyloid formation and/or the induction of amyloid degradation can be an important therapeutic tool for all pathological disorders associated with amyloidosis including AL amyloidosis and neurodegenerative disorders of the Alzheimer's type.
More particularly, the present invention provides the use in the manufacture of a medicament for use in the treatment of amyloidosis of an anthracyclinone of formula A ##STR1## wherein R.sub.1 represents: C.sub.5-6 cycloalkyl or CH.sub.2 Ph with the phenyl (Ph) ring optionally substituted by 1, 2 or 3 substituents selected from F, Cl, Br, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy and CF.sub.3 ; or alkyl or Ph optionally substituted by 1, 2 or 3 substituents selected from halogen, such as F, Cl or Br, and C.sub.1 -C.sub.6 alkyl; R.sub.6 is as above defined; in which X is CO, CH.sub.2, CHOH or a group of formula ##STR2## in which m is 2 or 3 and R.sub.8 is: hydrogen or hydroxy; substituted with hydroxy, CN, COR.sub.11, COOR.sub.11, CONR.sub.11 R.sub.12, O(CH.sub.2).sub.n NR.sub.11 R.sub.12 (n is 2 to 4) or NR.sub.11 R.sub.12 in which R.sub.11 and R.sub.12 are each independently selected from hydrogen, a C.sub.1 -C.sub.12 alkyl or C.sub.2 -C.sub.12 alkenyl group or phenyl optionally substituted by one or more, for example 1, 2 or 3, substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, F, Br, Cl, CF.sub.3, OH, NH.sub.2 or CN, or OH wherein R.sub.11 is as above defined, substituted on the phenyl ring by one or more, for example 1, 2 or 3, substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, F, Br, Cl, CF.sub.3, OH, NH.sub.2 or CN, or R.sub.12, CONR.sub.11 COOR.sub.12 or SO.sub.2 R.sub.12 in which R.sub.11 and R.sub.12 are as above defined, or attached form: C.sub.1 -C.sub.4 alkoxy, C.sub.2 -C.sub.6 alkenyl or phenyl optionally substituted by one or more, for example 1, 2 or 3, substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, F, Br, Cl, CF.sub.3, OH, NH.sub.2 or CN, or substituted by OH, NH.sub.2, COOH, COOR.sub.11, or CONR.sub.11 R.sub.12 wherein R.sub.11 and R.sub.12 are as above defined, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl or phenyl optionally substituted by one or more, for example 1, 2 or 3, substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, F, Br, Cl, CF.sub.3, OH, NH.sub.2 or CN; defined; substituted by nitro, amino or NR.sub.9 R.sub.10 as above defined; ##STR3## wherein R.sub.13 represents hydrogen, COR.sub.11 wherein R.sub.11 is as above defined, or a peptidyl residue and R.sub.14 is halogen or a group of formula OSO.sub.2 R.sub.7 wherein R.sub.7 is as above defined; or ##STR4## wherein E is a group of formula COOR.sub.11 or CONR.sub.9 R.sub.10 in which R.sub.9, R.sub.10 and R.sub.11 are as above defined; and NR.sub.9 R.sub.10 wherein R.sub.6, R.sub.9 and R.sub.10 are as above defined, or a group of formula E: ##STR5## wherein R.sub.6, R.sub.9 and R.sub.10 are as above defined and p is from 1 to 6; and the pharmaceutically acceptable salts thereof.
In a further aspect of the present invention there are provided novel anthracyclinones of the formula A as above defined, with the following provisos: are as above defined under a) to c) or e) to h) when R.sub.1 is H, OH or OCH.sub.3, R.sub.2 is H, R.sub.3 is OH and R.sub.4 is a group of formula XCH.sub.2 OH or XCH.sub.3 wherein X is as above defined; R.sub.2 is H, OH, COOCH.sub.3 and R.sub.4 is a group of the formula, XCH.sub.3 or XCH.sub.2 OH, wherein X is as above defined; phenyl, benzyl, C.sub.1 -C.sub.6 alkyl or C.sub.5 -C.sub.6 cycloalkyl when R.sub.1 is H or O
REFERENCES:
Hartmann et al, Chemical Abstracts, vol. 126, No. 144,048 (1997).
Sumitomo, Chemical Abstracts, vol. 103, No. 141,751 (1985).
Povarov et al, Chemical Abstracts, vol. 91, No. 20926 (1979).
Ballinari Dario
Bandiera Tiziano
Caruso Michele
Lansen Jacqueline
Suarato Antonino
Pharmacia & Upjohn S.p.A.
Ramsuer Robert W.
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