Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1992-10-23
1994-11-08
Tsang, Cecilia
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514389, 514369, 514376, 544299, 544306, 5483171, 5483191, 548183, 548227, A61K 31515, C07D23902
Patent
active
053627334
DESCRIPTION:
BRIEF SUMMARY
The invention relates to new catechol derivatives and pharmaceutically acceptable salts and esters thereof which are useful as medicinal antioxidants. The invention also relates to pharmaceutical compositions containing said compounds and to the method of the preparation of the same.
Medicinal antioxidants are compounds that may be used for the prevention or treatment of tissue damage induced by lipid peroxidation. It is generally believed that cellular damage by oxygen derived radicals, especially those associated with lipid peroxidation, is a significant factor in heart diseases, rheumatoid arthritis, cancer, certain inflammatory diseases, rejection reactions in transplantation, ischemia and even in the aging process.
EP-A-343643 describes pharmaceutical compositions comprising the compounds of formula ##STR3## wherein Ar is (i) phenyl unsubstituted, (ii) phenyl substituted by from one to three of lower alkyl, lower alkoxy, hydroxy, halogen, trifluoromethyl, NR.sub.10 R.sub.11, wherein R.sub.10 and R.sub.11 are independently hydrogen or lower alkyl, NO.sub.2 , mercapto, or lower alkylthio, (iii) naphthyl; (iv) benzofuranyl, (v) benzothiophenyl, (vi) 2- or 3-thienyl, (vii) 2-or 3-indolyl, (viii) 2-or 3-furanyl, or (ix) 2-, 3-, or 4-pyridyl Y and Y.sub.1 is oxygen or sulfur; X is sulfur, oxygen, NH or NCH.sub.3 and X.sub.1 is NH or NCH.sub.3 and pharmaceutically acceptable salts thereof which are stated to be 5-lipoxygenase and/or cyclooxygenase inhibitors. Japanese patent application No. 1052765, which has been referred to in Chemical Abstracts (CA 111(17)153788y) discloses thiazolidinone derivatives which are useful as aldose reductase inhibitors. Gupta et al. in Eur. J. Med. Chem. - Chim. Ther., 17 (5), 448-52, 1982 and Srivastava et al. in Pharmazie, 36(4), 252-3, 1981 disclose 2-thioxo-4,6-pyrimidinedione compounds having anticonvulsant activity. Sohda et al. in Chem. Pharm. Bull., 31(2), 560-9, 1983 discloses 2,4-thioxolidione derivatives having antiulcer activity.
The compounds of the present invention may be represented by the formula I ##STR4## wherein R.sub.1 is an electronegative substituent such as nitro, halogeno or cyano group and R.sub.2 is a group selected from ##STR5## wherein R is hydrogen, or an alkyl, cycloalkyl, aralkyl or aryl group, wherein X.sub.1, X.sub.2, Y and Z are independently oxygen, sulfur or NR wherein R may be as defined above. In one embodiment, R.sub.2 is a group containing a five membered heterocyclic ring which is of formula ##STR6## in which X.sub.1 and X.sub.2 are both NR, wherein R is hydrogen or alkyl, Y is oxygen or sulfur and Z is oxygen or sulfur. Preferred ring systems include 2-thioxoimidazolidin-5-ones and 2,5-imidazolidin-5-ones. Examples of such compounds include 4-[(3,4-dihydroxy-5-nitrophenyl)methylidene]-2-thioxoimidazolidin-5-one; 4-[(3,4-dihydroxy-5-chlorophenyl)-methylidene]-2-thioxoimidazolidin-5-one; 4-[(3,4-dihydroxy-5-nitrophenyl)methylidene]-2,5-imidazolidindione and 4-[(3,4-dihydroxy-5-cyanophenyl)methylidene]-2-thioxoimidazolidin-5-one.
In another embodiment R.sub.2 is the group ##STR7## in which X.sub.1, Y, and Z are independently oxygen or sulfur and X.sub.2 is NR, in which R is hydrogen or alkyl. Preferred ring systems include 2-thioxothiazolidin-4-ones; 3-methyl-2-thioxothiazolidin-4-ones; thiazolidin-2,4-diones; 4-thioxo-2-oxazolidinones and 4-thioxithiazolidin-2-ones. Specific examples are 5-[(3,4-dihydroxy-5-nitrophenyl)-methylidene]-2-thioxothiazolidin-4-one; 5-[(3,4-dihydroxy-5-nitrophenyl)methylidene]-3-methyl-2-thioxothiazolidin- 4-one; 5- [(3,4-dihydroxy-5-nitrophenyl)methylidene]-thiazolidin-2,4-dione; 5-[(3,4-dihydroxy-5-chlorophenyl)-methylidene]-thiazolidin-2,4-dione; 5-[(3,4-dihydroxy-5-nitrophenyl)methylidene]-4-thioxo-2-oxazolidinone; 5-[(3,4-dihydroxy-5-nitrophenyl)methylidene]-4-thioxothiazolidin-2-one and 5-[(3,4-dihydroxy-5-cyanophenyl)-methylidene]-2-thioxothiazolidin-4- one.
In another embodiment R.sub.2 is the group ##STR8## in which X.sub.1 and Z are independently oxygen or sulfur and Y and X.sub.2 are NR, wherein R i
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Backstrom Reijo
Honkanen Erkki
Korkolainen Tapio
Linden Inge-Britt
Nissinen Erkki
Orion-yhtyma Oy
Tsang Cecilia
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