公开(公告)号：US06593300B1

公开(公告)日：2003-07-15

申请号：US09423006

申请日：2000-02-07

申请人： Sandor Bajusz ,  Iren Veghelyi ,  Klara Nemeth ,  Eva Barabas ,  Attila Juhasz ,  Jozsef Lango ,  Emilia Lavich ,  Zsuzsanna Mohai ,  Imre Moravcsik ,  Zsuzsanna Taschler ,  Gabor Toth

发明人： Sandor Bajusz ,  Iren Veghelyi ,  Klara Nemeth ,  Eva Barabas ,  Attila Juhasz ,  Jozsef Lango ,  Emilia Lavich ,  Zsuzsanna Mohai ,  Imre Moravcsik ,  Zsuzsanna Taschler ,  Gabor Toth

IPC分类号： A61K3800

CPC分类号： C07K7/02 ,  A61K38/00 ,  C07K5/0202

摘要： The invention relates to a new (3R)-3-amino-4-carboxybutyraldehyde derivatives of general formula(I) wherein X represents a C1-4 alkyloxycarbonyl, an optionally substituted phenyl-(C1-2 alkyloxy)-carbonyl, a C1-4 alkylcarbonyl or an optionally substituted phenyl-(C1-3 alkyl)-carbonyl group, n represents 1 or 0, Y represents, in the case when n=1, a tetrapeptide of general formula Y4-Y3-Y2-Y1, a tripeptide of general formula Y3-Y2-Y1 or a dipeptide of general formula Y2-Y1 or an amino acid residue of general formula Y1, or in the case when n=0, an &agr;-hydroxyacyl-tripeptide of general formula Q4-Y3-Y2-Y1, an &agr;-hydroxyacyl-dipeptide of general formula Q3-Y2-Y1 or an &agr;-hydroxyacyl-aminoacyl residue of general formula Q2-Y1; wherein Y1-Y4 represent a residue selected from the group of the following L- or D-amino acids: alanine, alloisoleucine, cyclohexyl-glycine, phenyl-alanine, glutamine, histidine, isoleucine, leucine, lysine, methionine, pipecolic acid, proline, tyrosine and valine; and Q2-Q4 represent an acyl group selected from the following &agr;-hydroxyacids of R or S configuration: 2-cycloheptyl-2-hydroxy-acetic acid, 2-cyclohexyl-2-hydroxyacetic acid, 3-cyclohexyllactic acid, 3-phenyllactic acid, 2-hydroxy-3-methylbutyric acid, 2-hydroxy-3-methylvaleric acid, mandelic acid or lactic acid, and salts thereof formed with organic or inorganic bases, and pharmaceutical compositions containing the same. The compounds of general formula (I) of the invention are valuable inhibitors of the interleukin-1&bgr; converting enzyme.

摘要翻译： 本发明涉及通式（I）的新的（3R）-3-氨基-4-羧基丁醛衍生物，其中X代表C1-4烷氧基羰基，任意取代的苯基 - （C 1-2烷氧基） - 羰基， 4烷基羰基或任选取代的苯基 - （C 1-3烷基） - 羰基，n表示1或0，Y表示在n = 1的情况下，通式Y4-Y3-Y2-Y1的四肽，三肽 通式Y3-Y2-Y1或通式Y2-Y1的二肽或通式Y1的氨基酸残基，或在n = 0的情况下，通式为Q4-Y3-Y2的α-羟基酰基三肽 -Y1，通式为Q3-Y2-Y1的α-羟酰基二肽或通式为Q2-Y1的α-羟基酰基 - 酰基残基; 其中Y 1 -Y 4表示选自以下L-或D-氨基酸的残基：丙氨酸，异亮氨酸，环己基 - 甘氨酸，苯丙氨酸，谷氨酰胺，组氨酸，异亮氨酸，亮氨酸，赖氨酸，甲硫氨酸，哌可酸，脯氨酸 ，酪氨酸和缬氨酸; 和Q 2 -Q 4表示选自以下R或S构型的α-羟基酸的酰基：2-环庚基-2-羟基 - 乙酸，2-环己基-2-羟基乙酸，3-环己基乳酸，3-苯基乳酸 ，2-羟基-3-甲基丁酸，2-羟基-3-甲基戊酸，扁桃酸或乳酸，以及与有机或无机碱形成的盐，以及含有它们的药物组合物。 本发明通式（I）的化合物是白细胞介素-1β转换酶的有价值的抑制剂。