申请人:——
公开号:US20030171371A1
公开(公告)日:2003-09-11
New N-acyl homoserine lactone compounds of the formula (I) in whichR is an acyl group of the formula (II) wherein one of R
1
and R
2
is H and the other is selected from OR
4
, SR
4
and NHR
4
, wherein R
4
is H or 1-6C alkyl, or R
1
and R
2
together with the carbon atom to which they are joined form a keto group, and R
3
containing from 8 to 11 carbon atoms and is optionally substituted by one or more substituent groups selected from halo, 1-6C alkoxy, carboxy, 1-6C alkoxycarbonyl, carbamoyl optionally mono- or disubstituted at the N atom by 1-6C alkyl and NR
5
R
6
wherein each of R
5
and R
6
is selected from H and 1-6C alkyl or R
5
and R
6
together with the N atom form a morpholino or piperazino group, or and enantiomer thereof, with the proviso that R is not a 3-oxododecanoyl group, having immuosuppressant properties are disclosed. The compounds are shown to have an inhibitory effect on lymphocyte proliferation and down-regulate TNF-&agr; secretion by monocytes/macrophages in the animal body, including the human body. Pharmaceutical composition comprising N-acyl homoserine lactones are also described.
1
公开了式(I)的新的N-酰基高丝氨酸内酯化合物,其中R是式(II)的酰基,其中R1和R2中的一个为H,另一个选择自OR4、SR4和NHR4,其中R4为H或1-6C烷基,或者R1和R2与它们结合的碳原子一起形成酮基,而R3含有8至11个碳原子,并且可以被一个或多个取代基选自卤素、1-6C烷氧基、羧基、1-6C烷氧羰基、在N原子上可能被1-6C烷基单独或二取代的氨基和NR5R6,其中R5和R6中的每一个选择自H和1-6C烷基或R5和R6与N原子一起形成吗啡环或哌嗪环,或其对映体,但R不是3-氧代十二酰基基团。这些化合物具有免疫抑制特性,已经表明这些化合物对淋巴细胞增殖具有抑制作用,并且在动物体内,包括人体内,下调单核细胞/巨噬细胞的TNF-α分泌。还描述了包含N-酰基高丝氨酸内酯的制药组合物。