New 2-thio-1,4-naphthoquinone derivatives, obtained by culturing alpha-Proteobacterium MBIC3368, are angiogenesis inhibitors useful e.g. for combating tumor diseases and neointimal hyperplasia

摘要

2-Thio-1,4-naphthoquinone derivatives (I) and their salts and solvates are new. 2-Thio-1,4-naphthoquinone derivatives of formula (I) and their salts and solvates are new. [Image] R 1H; 1-18C alkyl or 2-18C alkenyl (both linear, branched or cyclic and optionally mono- or polysubstituted); or acyl (e.g. CHO, COMe, COCCl 3, fumaryl, maleyl, succinyl, benzoyl or branched or heteroatom- or aryl-substituted acyl); R 2- R 6as for R 1; optionally cyclic alkoxy (e.g. 1-4C alkoxy); alkylthio (e.g. SMe or SEt); sulfonyl group (e.g. SO 3H, SO 2Me, SO 2CF 3, SO 2C 6H 4CH 3or SO 2C 6H 4CH 2Br); nitrogen-containing substituent (e.g. NH 2, NHR, NRR', NC or NO 2); or halo, CN or hetero-substituent; R, R' : alkyl, aryl, heteroaryl or alkenyl. An independent claim is included for the preparation of (I). ACTIVITY : Cytostatic; Antibacterial; Vasotropic. 2-Methylthio-1,4-naphthoquinone (Ia) had D 500.07 Microg/ml for inhibition of proliferation of L5178y (mouse lymphoma) cells. MECHANISM OF ACTION : Thrombospondin (TSP) binding ligand; CD36-TSP system modulator; angiogenesis inhibitor.