Spirocycles inhibitors metalloprotease

 

The invention relates to new spirochetes formula Iwhere Ar is phenyl, substituted phenyl where the substituents are: alkoxy, alkyl, alkoxyalkyl, phenoxy, halogen, pyridyloxy, alkoxyalkane, halogenfree; R1- H; R2- H1-C4alkyl; W represents O or one or more1-C4alkyl fragments; Y is independently one or more members of the group consisting of H2, SR3, alkoxy; R3- H, alkyl; Z is a carbocyclic or heterocyclic Spiro-fragment with a 3-7 member ring system, where the heterocyclic fragment includes 2 oxygen atom or sulfur, or one nitrogen atom and spirits may be unsubstituted or substituted by hydroxy, C1-C4the alkyl, benzyloxy; n=1-3; optical isomers, diastereomers or enantiomers or its pharmaceutically acceptable salt. Compound I inhibited metalloprotease, which allows their use in pharmaceutical compositions for treating or preventing diseases associated with increased activity of metalloprotease. 2 C. and 8 C.p. f-crystals, 5 PL.

Description text in facsimile form (see graphic part).

Form>where AG represents unsubstituted or substituted phenyl, where the substituents are alkoxy, alkyl, alkoxyalkyl, phenoxy, halogen, pyridyloxy, alkoxyalkane, halogenfree; R1is hydrogen; R2represents hydrogen, C1-C4alkyl; W is zero or one or more1-C4alkyl fragments; Y is independently one or more members of the group consisting of hydrogen, SR3and alkoxy;
R3represents hydrogen, alkyl;
Z represents a carbocyclic or heterocyclic Spiro-fragment with a 3-7 member ring system, where the heterocyclic fragment includes 2 oxygen atom or sulfur, or one nitrogen atom and spirits may be unsubstituted or substituted by hydroxy, C1-C4the alkyl, benzyloxy;
n = 1-3;
optical isomers, diastereomers or enantiomers of the compounds of formula (I) or their pharmaceutically acceptable salts.

2. Connection on p. 1, in which Y is independently one or more members of the group consisting of hydrogen and alkoxy.

3. The compound according to any one of the preceding paragraphs, in which AG is substituted phenyl.

4. The compound according to any one of the preceding testuya points, in which W represents one or more hydrogen atoms or one or more1-C4Akilov.

6. The compound according to any one of the preceding paragraphs, in which the Spiro-fragment Z forms a 5-7-membered ring with the carbon atom to which it is attached.

7. The compound according to any one of the preceding paragraphs, in which spirits is substituted ring.

8. The compound according to any one of the preceding paragraphs, in which Z has 2 oxygen atom or sulfur.

9. The compound according to any one of the preceding paragraphs for the manufacture of a pharmaceutical composition inhibiting metalloprotease.

10. The method of prevention or treatment of diseases associated with undesirable increased activity of metalloprotease the mammalian subject, comprising the introduction of a specified subject an effective amount of a compound according to any one of the preceding paragraphs.

 

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The invention relates to medicine, namely to the chemical-pharmaceutical industry
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