RU99106583A - BIDENTATIC METALLOPROTEASIC INHIBITORS - Google Patents

Claims (1)

1. The compound having a structure in accordance with formula I

where n is an integer from 1 to 3, and 0-2 additional atoms selected from O, N or S can be in the structure of this ring instead of carbon, and where S is present, it can be in the form of S, SO or SO ₂ , and where N is present, it is in the form of NR ₅ , and R _{5 is} selected from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, SO ₂ R ₁₀ , COR ₁₁ , CSR ₁₂ , PO (R ₁₃ ) ₂ ;
Z is independently one or more (CH ₂ ) _m (CR ₁ R ₂ ) _o SR ₃ ;
R ₁ is independently hydrogen, alkyl, CH ₂ SR ₃ or CH ₂ C (W) R ₄ , and R ₄ is alkoxy, hydroxy, NR ₅ , alkylthio or thio; and R ₅ independently represents one or more such radicals as heterocycloalkyl, alkyl, aryl, heteroalkyl, heteroaryl, hydrogen, or together with W can form a heterocyclic ring;
R ₂ is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, heterocycloalkylene, aryl, or heteroaryl;
W is O or S;
R ₃ denotes hydrogen, alkyl, aryl, heteroaryl;
m and o denote integers independently selected from 0, 1 and 2;
Y means independently one or more hydrogens, hydroxy, oxo, spirofragment, SOR ₆ , SO ₂ R ₁₀ , alkoxy, aryloxy, alkyl, aryl, heteroaryl, COR ₁₁ , CSR ₁₂ , amino, where amino has the formula NR ₈ R ₉ , R ₈ and R _{9 are} independently selected from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, OR ₃ , SO ₂ R ₁₀ , COR ₁₁ , CSR ₁₂ , PO (R ₁₃ ) ₂ ;
R ₆ is alkyl, aryl, heteroaryl;
R ₁₀ is alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino;
R ₁₁ is hydrogen, alkoxy, aryloxy, heteroaryloxy, heteroalkyloxy, alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, and alkylarylamino;
R ₁₂ is alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino;
R ₁₃ is alkyl, aryl, heteroaryl, heteroalkyl;
Ar is substituted or unsubstituted alkyl, aryl, carbocyclyl, heterocyclyl, or heteroaryl; or its optical isomer, diastereomer, enantiomer or pharmaceutically acceptable salt or biohydrolyzable ester, amide or imide. 2. The compound according to claim 1, where Z is selected from thio, alkylthio, thioalkyl, R ₃ SCH ₂ CH (SR ₃ ) - and R ₄ C (O) CH ₂ CH (SR ₃ ) -. 3. The compound according to any one of the preceding claims:

4. The compound according to any one of the preceding claims:

5. A compound according to any one of the preceding claims, wherein Ar is phenyl or substituted phenyl.  6. A compound according to any one of the preceding claims, wherein Ar is substituted phenyl, substituted hydroxy, alkoxy, nitro or halogen.  7. The compound according to any one of the preceding paragraphs, where n is 1 or 2. 8. A compound according to any one of the preceding claims, wherein Y is one or more hydrogens or C ₁ -C ₄ -alkyl.  9. A compound according to any one of the preceding claims, having two Z fragments selected from thio and thiomethyl. 10. The compound according to any one of the preceding claims, wherein Z is CH ₃ OC (O) CH ₂ CH (SH) - or R ₃ SCH ₂ CH (SH) -, and R ₃ is heteroaryl.  11. The use of a compound according to any one of the preceding claims for the preparation of a pharmaceutical composition.  12. A method of preventing and treating a disease associated with undesirable metalloprotease activity in a mammal, comprising administering to the mammal a safe and effective amount of a compound according to any one of the preceding claims.