RU99106412A - 1,3-DIGETEROCYCLIC INHIBITORS METALLOPROTEASIS - Google Patents

Claims (9)

1. The compound having a structure corresponding to formula (I)

where R ₁ is H;
R ₂ represents hydrogen, alkyl or acyl,
Ar is COR ₃ or SO ₂ R ₄ ; and
R ₃ is alkoxy, aryloxy, heteroaryloxy, alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino and alkylarylamino;
R ₄ is alkyl, heteroalkyl, aryl or heteroaryl, substituted or unsubstituted;
X is O, S, SO, SO ₂ or NR ₅ , where R _{5 is} independently selected from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, SO ₂ R ₆ , COR ₇ , CSR ₈ , PO (R ₉ ) ₂ or optionally form a ring with Y or W; and
R ₆ is alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino;
R ₇ represents hydrogen, alkoxy, aryloxy, heteroaryloxy, alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino and alkylarylamino;
R ₈ is alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino;
R ₉ is alkyl, aryl, heteroaryl, heteroalkyl;
W represents hydrogen or one or more lower alkyl moieties or a heterocycle or represents an alkylene, arylene or heteroarylene bridge between two adjacent or non-adjacent carbon atoms (thereby forming a fused ring);
Y is independently one or more of hydrogen, hydroxy, SR ₁₀ , SOR ₄ , SO ₂ R ₄ , alkoxy, amino, and amino has the formula NR ₁₁ R ₁₂ , where R ₁₁ and R _{12 are} independently selected from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, SO ₂ R ₆ , COR ₇ , CSR ₈ , PO (R ₉ ) ₂ ; and
R ₁₀ is hydrogen, alkyl, aryl, heteroaryl;
Z is absent or represents a spiro moiety or an oxo group substituted on a heterocyclic ring;
n is 1-4
this structure also includes the optical isomer, diastereomer or enantiomer of the compound of formula (I) or its pharmaceutically acceptable salt or bio-hydrolysable amide, ester or imide. 2. The compound according to claim 1, where X is O, S, SO, SO ₂ or NR ₅ , where R _{5 is} independently selected from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, SO ₂ R ₇ , COR ₈ , CSR ₉ . 3. The compound according to any one of the preceding claims, wherein Ar is SO ₂ R ₄ and R ₄ is alkyl, heteroalkyl, aryl or heteroaryl, substituted or unsubstituted.  4. A compound according to any one of the preceding claims, Ar is phenyl or substituted phenyl.  5. The compound according to any one of the preceding claims, wherein Ar is phenyl, substituted by hydroxy, alkoxy, nitro or halogen. 6. A compound according to any one of the preceding claims, wherein W represents one or more hydrogen atoms or one or more C ₁ -C ₄ alkyls. 7. The compound according to any one of the preceding paragraphs, where W is a geminal C ₁ -C ₄ alkyl.  8. A compound according to any one of the preceding claims, wherein Z is an oxo or spiro moiety substituted in a heterocyclic ring.  9. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.