The nitriles of dipeptides

 

(57) Abstract:

The invention relates to a new group of individual compounds of the formula I

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where R denotes optionally substituted aryl, aryl(ness.)alkyl, (ness.)alkenyl, (ness.)quinil or N-containing heterocyclyl; R2and R3each independently of one another denotes hydrogen or optionally substituted (ness.)alkyl, aryl(ness.)alkyl, cycloalkyl(ness.)alkyl, or R2and R3together denote (NISS. )alkylen so that together with the carbon atom to which they are linked, form a ring; R4and R5each independently of the other represents H or optionally substituted (ness.)alkyl, aryl(NISS. )alkyl, or R4and R5together denote (ness.)alkylen so that together with the carbon atom to which they are linked, form a ring, or R4denotes H, R5denotes Deputy formula X2-Ar-Z, where X2stands WITH2-C7alkylene containing in-chain O, S, or SOP, Ar denotes Allen, Z denotes carboxyl or esterified carboxyl; X1denotes-C(O)- or-S(O)2-, Y represents oxygen, L denotes an optionally substituted-Het-, -Het-CH2or With the definitions indicated carbocyclic or heterocyclic aryl, its physiologically acceptable and biodegradable ester or salt; tert-method of producing compounds of the formula I on p. 1. The described compounds are effective inhibitors of containerizing. 5 s and 5 C.p. f-crystals, 11 PL.

Description text in facsimile form (see graphic part).

1. The compound of the formula I

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where R denotes optionally substituted aryl, aryl (NISS. )alkyl, (NISS. )alkenyl, (NISS. )quinil or N-containing heterocyclyl;

R2and R3each independently of one another denotes hydrogen or optionally substituted (NISS. )alkyl, aryl(NISS. )alkyl, cycloalkyl (NISS. ) alkyl, or R2and R3together denote (NISS. )alkylen so that together with the carbon atom to which they are linked, form a ring;

R4and R5each independently of the other represents H or optionally substituted (NISS. )alkyl, aryl (NISS. )alkyl, or R4and R5together denote (NISS. )alkylen so that together with the carbon atom to which they are linked, form a ring, or R4denotes H, R5denotes Deputy formula X2-Ar-Z, where X2stands WITH2-C7alkylene containing chain which denotes-C(O)- or-S(O)2-;

Y denotes oxygen;

L denotes an optionally substituted-Het-, -Het-CH2- or-CH2-t-where Het denotes a heteroatom selected from O and N;

x denotes 0 or 1;

the aryl in the above definitions indicated carbocyclic or heterocyclic aryl,

its physiologically acceptable and biodegradable ester or salt.

2. The compound of formula II under item 1

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where R20denotes optionally substituted aryl or N-substituted heterocyclyl;

R22and R23together with the carbon atom to which they are bound, form an optionally substituted cycloalkyl group;

R24and R25each independently of the other represents H or optionally substituted (NISS. )alkyl, aryl(NISS. )alkyl, or R24and R25together with the carbon atom to which they are bound, form an optionally substituted cycloalkyl group;

X1denotes-C(O)-;

L' denotes optionally substituted-t-CH2- or-CH2-t, where Het denotes a heteroatom selected from O and N;

x denotes 1 or 0,

its pharmaceutically acceptable and biodegradable ester or salt.

3. The compound of formula Ito acid;

R32and R33each independently of one another denotes hydrogen, aryl (NISS. )alkyl;

R34denotes hydrogen or (NISS. )alkyl;

X2, Ar and Z have the values listed in paragraph 1,

as well as its physiologically acceptable salts and esters.

4. The compound of formula IV under item 1

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where R40denotes a substituted phenyl or heterocyclic aryl, mono - or dicarbollide or heterocyclic aryl(NISS. )alkyl or (NISS. )alkenyl or N-containing heterocyclyl;

R42denotes hydrogen or (NISS. )alkyl;

R43denotes a carbocyclic or geterotsiklicheskikh aryl(NISS. )alkyl;

R44and R45each independently of one another denotes hydrogen or (NISS. )alkyl, or R44and R45together denote (NISS. )alkylen,

as well as its physiologically acceptable salts and esters.

5. Connection on p. 2 of the formula V

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in which the symbols have the meanings specified in paragraph 1,

and its physiologically acceptable and biodegradable esters and salts.

6. Connection on p. 3, formula V'

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in which the symbols have the meanings specified in paragraph 3,

and its physiologically acceptable and split words the data in p. 4,

and its physiologically acceptable and biodegradable esters and salts.

8. The method of obtaining the compounds of formula I on p. 1, including the conversion of the amide of formula VI

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in which R, R2, R3, R4, R5, L, X1and x have the meanings specified in paragraph 1,

in the nitrile of the formula I, and optionally provides temporary protection of all interfering reactive groups, followed by separation of the resulting compounds according to the invention, and optionally transforming any resulting compound into another compound of the invention and/or, if necessary, conversion of the compounds formed in salt or a resulting salt into the free acid, base or another salt.

9. The method of obtaining the compounds of formula I under item 1, comprising the reaction of condensation of the compounds of formula VII

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in which R4and R5have the values listed in paragraph 1,

with the acid of formula VIII

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in which R, R2, R3, L, X and x have the meanings specified in paragraph 1,

if its reactive derivative, and if necessary, provides temporary protection of all interfering reactive groups, followed by separation to be placed in another connection according to the invention and/or, if necessary, conversion of the compounds formed in salt or a resulting salt into the free acid, the base or another salt.

10. The method of obtaining the compounds of formula I under item 1, comprising the reaction of condensation of compounds of formula Ia

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in which R2, R3, R4and R5have the values listed in paragraph 1,

acid, which corresponds to the group R-[L]xX1or its reactive derivative, and if necessary, provides temporary protection of all previous reactive groups, followed by separation forming compounds according to the invention, and optionally conversion of the resulting compound into another compound of the invention and/or of the necessity of making the compounds formed in salt or a resulting salt into the free acid, base or another salt.

 

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