Thiosuccinic acid derivatives and the use thereof
View Patent ↗The present invention relates to compounds of the formula (I) wherein X 1 and X 2 independently represent O, NH or S, R 1 and R 2 are independently selected from the group consisting of a C 1 -C 30 hydrocarbyl group, an amino acid bonded via an amide bond or a peptide bonded via an amide bond each having up to 200 amino acids, the conjugated residue X 1 or X 2 in this case being NH, and hydrogen, both radicals R 1 and R 2 preferably not being H, wherein R 3 is a residue selected from group consisting of —S—R 6 , wherein R 6 is a C 1 -C 30 hydrocarbyl group, at least one of R 1 and R 2 not being H when X 1 and X 2 are oxygen, —S—CH 2 —CH(NH 2 )(COOH) (cysteine-S-yl), a homologue or derivative (e.g. N-acetyl cysteine-S-yl) thereof, a peptide having up to 200 amino acids which contains at least one amino acid radical with a thiol group, preferably a cysteine radical, and is bonded via the thio sulfur, preferably via the cysteine sulfur (peptide-S-yl), coenzyme A which is bonded via a thiol group or fragments thereof, acyl carrier protein bonded via a thiol group, and dihydrolipoic acid bonded via a thiol group, and pharmaceutically acceptable salts thereof. The present invention also relates to the use of these compounds for preparing a drug and drugs containing the same.
1. A compound of the formula (I)
wherein X 1 and X 2 are independently chosen from O, NH, and S,
R 1 and R 2 are both methyl, and
R 3 is —S—CH 2 —CH(NH 2 )(COOH) or N-acetylcysteine-S-yl,
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 wherein X 1 and X 2 are oxygen.
3. The compound according to claim 1 , wherein R 3 is N-acetylcysteine-S-yl.
4. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 1 .
5. The pharmaceutical composition according to claim 4 , wherein the pharmaceutical composition is in a form suitable for oral, rectal, transdermal, dermal, ophthalmological, nasal, pulmonary, or parenteral application.
6. The pharmaceutical composition according to claim 4 , wherein the pharmaceutical composition is in a form suitable for parenteral application.
7. The pharmaceutical composition according to claim 4 , wherein the pharmaceutical composition is in a form chosen from tablets, coated tablets, capsules, granulates, solutions for drinking, liposomes, nano-particles, nanocapsules, micro-capsules, micro-tablets, pellets, powders, granulate filled in capsules, micro-tablets filled in capsules, pellets filled in capsules, nano-particles filled in capsules, and powder filled in capsules.
8. A method of treating a disease comprising administering to a patient in need of such treatment, a compound or a pharmaceutically acceptable salt thereof as defined in claim 1 , wherein the disease is chosen from
an autoimmune disease chosen from polyarthritis, multiple sclerosis, graft-versus-host reactions, juvenile-onset diabetes, Hashimoto's thyroiditis, Grave's disease (Basedow disease), systemic Lupus erythematodes (SLE), Sjogren's syndrome, pernicious anaemia, and chronic active (=lupoid) hepatitis;
transplantation;
mitochondrial diseases chosen from Parkinson syndrome, Alzheimer's disease, Chorea Huntington disease, retinopathia pigmentosa, and forms of mitochondrial encephalomyopathies;
NF-kappaB mediated diseases chosen from progressive systemic sclerodermia, osteochondritis syphilitica (Wegener's disease), cutis marmorata (livedo reticularis), Behcet disease, panarteritis, colitis ulcerosa, vasculitis, osteoarthritis, gout, arteriosclerosis, Reiter's disease, pulmonary granulomatosis, types of encephalitis, endotoxic shock (septic-toxic shock), sepsis, pneumonia, encephalomyelitis, anorexia nervosa, hepatitis, Rennert T-lymphomatosis, mesangial nephritis, post-angioplastic restenosis, reperfusion syndrome, cytomegaloviral retinopathy, adenoviral diseases, adenoviral pharyngoconjunctival fever, adenoviral ophthalmia, AIDS, Guillain-Barré syndrome, post-herpetic or post-zoster neuralgia, inflammatory demyelinising polyneuropathy, mononeuropathia multiplex, mucoviscidosis, Bechterew's disease, Barett oesophagus, EBV (Epstein-Barr virus) infection, cardiac remodeling, interstitial cystitis, diabetes mellitus type II, radiosensitisation of malignant tumours, multi-resistance of malignant cells to chemotherapeutic agents (multidrug resistance in chemotherapy), granuloma annulare, and cancers;
psoriasis, psoriatic arthritis, neurodermitis, and enteritis regionalis Crohn;
cardiac insufficiency, left-ventricular failure, cardiac infarction, cardiac arrest (cardioplebicum), ischaemia, and angina pectoris; and
chronic obstructive pulmonary diseases and asthma.
9. The method of claim 8 , wherein the disease is hepatitis and is selected from the group consisting of acute hepatitis, chronic hepatitis, toxic hepatitis, alcohol-induced hepatitis, viral hepatitis, jaundice, and cytomegaloviral hepatitis.
10. The method of claim 8 , wherein the disease is an adenoviral disease that is an adenoviral cold.
11. The method of claim 8 , wherein the disease is cancer and is selected from the group consisting of mamma carcinoma, colon carcinoma, melanoma, primary liver cell carcinoma, adenocarcinoma, kaposi's sarcoma, prostate carcinoma, leukaemia, acute myeloid leukaemia, multiple myeloma (plasmocytoma), Burkitt lymphoma, and Castleman tumour.