公开(公告)号：US5252560A

公开(公告)日：1993-10-12

申请号：US905933

申请日：1992-06-29

申请人： Peter L. Myers ,  Andrew B. McElroy ,  Michael Gregson ,  Peter J. Brown ,  Howard G. Davies ,  David H. Drewry ,  Michael A. Foley

发明人： Peter L. Myers ,  Andrew B. McElroy ,  Michael Gregson ,  Peter J. Brown ,  Howard G. Davies ,  David H. Drewry ,  Michael A. Foley

IPC分类号： A61K38/55 ,  A61K38/00 ,  A61P1/02 ,  A61P17/00 ,  A61P19/10 ,  A61P25/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07D209/48 ,  C07D209/66 ,  C07D471/04 ,  C07D471/14 ,  C07D487/04 ,  C07D487/14 ,  C07K1/06 ,  C07K1/113 ,  C07K5/02 ,  C07K5/06 ,  C07K5/08 ,  A61K37/02 ,  C07D413/12

CPC分类号： C07K5/0222 ,  A61K38/00

摘要： Compounds are described of the formula ##STR1## wherein: R.sup.1 is C.sub.3-6 alkyl or C.sub.1-3 alkylthioC.sub.1-3 alkyl;R.sup.2 is an optionally substituted C.sub.1-6 alkyl or C.sub.1-6 alkoxy group, aryl, heteroaryl, arylC.sub.1-4 alkyl, heteroarylC.sub.1-4 alkyl or a side-chain of a natural .alpha.-amino acid;R.sup.3 is hydrogen, C.sub.1-6 alkyl, CHR.sup.4 COR.sup.5 (where R.sup.4 is a side-chain of a natural .alpha.-amino acid and R.sup.5 is hydroxyl, C.sub.1-6 alkoxy or NHR.sup.6 where R.sup.6 represents a hydrogen atom or a C.sub.1-6 alkyl group) or a group (CH.sub.2).sub.n X (where n is 1 to 6 and X is hydroxyl, C.sub.1-4 alkoxy, heteroaryl or a group NR.sup.7 R.sup.8 where R.sup.7 and R.sup.8 are each hydrogen or C.sub.1-6 alkyl or the group NR.sup.7 R.sup.8 forms a 5 to 7 membered cyclic amine); andHet is an optionally substituted cyclic imide where the cyclic imide ring system has the formula (i), (ii) or (iii) ##STR2## in which A, B, C and D are each CH or 1 or 2 of A, B, C and D represents N and the others represent CH, and E and F may each independently represent CH or N; and physiologically acceptable salts and solvates thereof.These compounds inhibit metalloproteases involved in tissue degradation. Compounds of the invention may be formulated for use in a variety of conditions involving tissue degradation including arthropathy, dermatological conditions, bone resorption, inflammatory diseases, tumour invasion and multiple sclerosis and related diseases involving myelin degradation, and in the promotion of wound healing.