Use of a phthalimide derivative or sulfonamide derivative In the preparation of a drug for the treatment of diseases which require reducing the levels of the tumor necrosis factor alfa factor and an exogenous source of nitric oxide
NOVELTY – In the preparation of a drug for the treatment of diseases which require reducing the levels of the tumor necrosis factor alfa factor (TNF- alpha factor) and an exogenous source of nitric oxide, a phthalimide derivative or sulfonamide derivative is used. USE – In the preparation of a drug for the treatment of diseases e.g. sickle-cell disease, which require reducing the levels of the TNF-a factor and an exogenous source of nitric oxide (Claimed). Also for increasing gamma-globin gene expression, and providing antiinflammatory and analgesic activities. ADVANTAGE – Upto now, there is no specific treatment for sickle-cell disease, all the known treatments are based on the use of drugs which minimize or fight against the symptomatology of sickle-cell disease. The present method provides a solution for the major limitations associated with the drug therapy of diseases which involve the need of reducing the levels of the TNF- alpha factor and the need of an exogenous source of nitric oxide, providing an alternative for the reduction of side and adverse effects of commonly-used compounds. The method overcomes the problems related with the major limitations and complications associated with the drug therapy conventionally used for the treatment of sickle-cell disease, thus improving the quality of life of the patient with sickle-cell disease. The new derivatives were obtained with good to excellent chemical yields, by employing a methodology characterized by having a few synthetic steps, from commercially-available compounds, which qualifies this methodology for industrial use. DETAILED DESCRIPTION – In the preparation of a drug for the treatment of diseases which require reducing the levels of the TNF-a factor and an exogenous source of nitric oxide, a phthalimide derivative of formula (I) or sulfonamide derivative of formula W’-R1SO2NHR2 (II) is used. W’=H, halo, NO2, NH2, OH, 1-6C (halo)alkoxy, 1-6C haloalkyl; R1=phenylene, benzyl, ethylbenzyl, thiophendiyl, furandiyl, pyrroldiyl, pyridindiyl, pyrazindiyl, pyrimidindiyl, benzothiophenylene, benzofurandiyl, indoldiyl, quinolindiyl, isoquinolindiyl, naphthylene, CH2-(2-thiophenyl), CH2-(3-thiophenyl), CH2-(2-furanyl), CH2-(3-furanyl), CH3CH2-(2-thiophenyl), CH3CH2-(3-thiophenyl), CH3CH2-(2-furanyl), CH3CH2-(3-furanyl); R’=O-NO2, SO2NHOH or furoxan; R=R1 or 1-7C alkyl; R2=OH, H, C(O)NHOH, C(=S)NHOH, C(O)NOH(Ph). INDEPENDENT CLAIMS are included for the following (1) preparing (P1) 4-amino-N-hydroxy-benzenesulfonamide (IIa) involving a) mixing, in a container, hydroxylamine hydrochloride, sodium bicarbonate and water; b) adding ethanol to the mixture obtained in step a; c) adding 4-(l,3 -dioxo-1,3-dihydro-2H-isoindol-2-yl)-benzenesulfonyl chloride to the mixture obtained in step b; (2) a pharmaceutical composition comprising (I) or (II) and a carrier; and (3) new isoindoles selected from 2-(3-nitrooxymethyl-phenyl)-isoindole-1,3-dione (Ia) and 2-(4-(2-nitrooxy)ethyl)-phenyl)-isoindole-1,3-dione (Ib).
Main Application Field
B02 (Fused ring heterocyclics.); B05 (Other organics – aromatics, aliphatic, organo-metallics, compounds whose substituents vary such that they would be classified in several of B01 – B05.); B07 (General – tablets, dispensers, catheters (excluding drainage and angioplasty), encapsulation etc, but not systems for administration of blood or saline or IV feeding etc.)
INVENTORS:
DOS SANTOS JEAN LEANDRO
CHUNG MAN CHIN
MOREIRA LIMA LIDIA
FERREIRA COSTA FERNANDO
LANARO CAROLINA
222_ANEMIA
Patent number: WO2009073940-A2;WO2009073940-A3;BR200705396-A2;EP2224922-A2;IN201001247-P3;KR2010114880-A;US2010324107-A1;CN101951901-A;ZA201004723-A;US2012157690-A1;US2012245364-A1;US8314255-B2;US8338474-B2;CN101951901-B;ZA201108106-A;EP2224922-A4
PATENT STATUS:
GRANTED
FOR ADDITIONAL INFORMATION:
parcerias@inova.unicamp.br
+55 (19) 3521-5207 / 2607
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