| 摘要 |
The invention relates to D-prolines of the formula or wherein R is SH, benzyl or phenyl, optionally substituted by hydroxy or lower alkoxy or ; the group R1 is hydrogen or halogen; X is -(CH2)n-; -CH(R2)(CH2)n-; -CH2O(CH2)n-; -CH2NH-; benzyl, -C(R2)=CH-; -CH2CH(OH)-; or thiazol-2,5-diyl; Y is-S-S-;-(CH2)n-;-O-;-NH-;-N(R2)-;-CH=CH-; -NHC(O)NH-; -N(R2)C(O)N(R2)-; -N¢CH2C6H3(OCH3)2!-; -N(CH2C6H5)-; -N(CH2C6H5)C(O)N(CH2C6H5)-; -N(alkoxyalkyl)-; -N(cycloalkyl-methyl)-; 2,6-pyridyl; 2,5-furanyl; 2,5-thienyl; 1,2-cyclohexyl; 1,3-cyclohexyl; 1,4-cyclohexyl; 1,2-naphthyl; 1,4-naphthyl; 1,5-naphthyl; 1,6-naphthyl; biphenylen; or 1,2-phenylen,1,3-phenylen and 1,4-phenylen, wherein the phenylen groups are optionally substituted by 1 - 4 substituents, selected from halogen, lower alkyl, lower alkoxy, hydroxy, carboxy, -COO-lower alkyl, nitrilo, 5-tetrazol, (2-carboxylic acid-pyrrolidin-1-yl)-2-oxo-ethoxy, N-hydroxycarbamimidoyl, 5-oxo-¢1,2,4!oxadiazolyl, 2-oxo-¢1,2,3,5!oxathiadiazolyl, 5-thioxo-¢1,2,4!oxadiazolyl and 5-tert-butylsulf anyl-¢1,2,4!oxadiazolyl; X' is -(CH2)n-; -(CH2)n CH(R2)-; -(CH2)n OCH2-; -NHCH2-; benzyl, -CH=C(R2)-; -CH(OH)CH2; or thiazol-2,5-diyl; R2 is lower alkyl, lower alkoxy or benzyl and n is 0-3, and to pharmaceutically acceptable salts and mono- and diesters thereof. The D-prolines of formula I-A and I-B can be used in the treatment or prevention of all forms of central and systemic amyloidosis. |
