Nk1/nk3 double agonists for treating schizophrenia

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

 

The text descriptions are given in facsimile form.

1. The use of compounds of General formula

,

where R means aryl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R′′, -NR′R′′, -NR′C(O)-alkyl, -NR′S(O)2-alkyl, or means heteroaryl selected from the group comprising pyridine-2 - or-3-yl, imidazolyl or oxazolyl, unsubstituted or substituted by alkyl, halogen or alkoxygroup;

R2and R3independently of one another denote hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3;

R4, R5independently of one another denote hydrogen, -(CR′R)1-(CR′R)1-(CR′R)a 0.1-OH or -(CR′R′′)1-(CR′R)1-(CR′R)a 0.1-alkyl, where R′ and R′ each carbon atom may be the same or may differ from each other, -C1,2-alkyl, -C(O)H, -(CH2)about-pilooski, unsubstituted or substituted by hydroxyl, -(CH2)1,2,3NR′R", -(CH2)1,2,3NR′C(O)-alkyl, -(CH2)1,2,3NR′S(O)2-alkyl, -(CH2)aboutS(O)-alkyl, -(CH2)oS-alkyl, -(CH2)oS(O)2-alkyl, -(CH2)oS(O)2-NR′R",

R′ means hydrogen, alkyl, -(CH2)aboutHE, -C(O)H, -C(O)-Ala is l, -C(O)-cycloalkyl, -S(O)2-alkyl, -S(O)2-halogen-alkyl, -S(O)-alkyl, -S-alkyl or-S(O)2-N-dialkyl,

R ' means hydrogen or alkyl; or

R4and R5together with the nitrogen atom to which they are linked, form a ring with -(CH2)3-5-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)oOH, =O, -Cho, -NR′R", where R′ and R" are as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)aboutNR'-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)NR′R", -(CH2)about-S(O)2-alkyl, -(CH2)o-S(O)-alkyl, -(CH2)about-S-alkyl, -(CH2)oS(O)2-NR′R", -(CH2)about-pyrrolidinyl or-C(O)NR′R"; or form a ring with -(CH2)1,2,3-NR′-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)oOH, =O, -Cho, -NR′R", where R′ and R" are as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2 3-5or substituted -(CH2)oNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)NR′R", -(CH2)about-S(O)2-alkyl, -(CH2)about-S(O)-alkyl, -(CH2)about-S-alkyl, -(CH2)o-S(O)2-NR′R", -(CH2)o-pyrrolidinyl or-C(O)NR′R"; or form a ring with -(CH2)1,2,3-O-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)oOH, =O, -CHO, -NR′R", where R′ and R" are as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)aboutNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)NR′R", -(CH2)about-S(O)2-alkyl, -(CH2)about-S(O)-alkyl, -(CH2)about-S-alkyl, -(CH2)o-S(O)2-NR′R", -(CH2)o-pyrrolidinyl or-C(O)NR′R"; or form a ring with -(CH2)1,2,3-S(O)0,1,2-(CH2)1,2,3-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)o OH, =O, -CHO, -NR′R", where R′ and R" are as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)aboutNR'-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)NR′R", -(CH2)about-S(O)2-alkyl, -(CH2)o-S(O)-alkyl, -(CH2)about-S-alkyl, -(CH2)o-S(O)2-NR′R", -(CH2)about- pyrrolidinyl or-C(O)NR′R"; or form a ring with CH2CH=CH-CH2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)oOH, =O, -CHO, -NR′R", where R′ and R" are as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)aboutNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)NR′R", -(CH2)about-S(O)2-alkyl, -(CH2)about-S(O)-alkyl, -(CH2)about-S-alkyl, -(CH2)o-S(O)2-NR′R", -(CH2)o-pyrrolidinyl or-C(O)NR′R"; or form a ring with -(CH2)2-S(O)2N(CH3)-CH2or-S(O)-O-(CH2)2,3 -;

or-NR4R5is

,,,

,,or

on means 0, 1, 2 or 3,

or pharmaceutically active acid additive salts for the preparation of drugs for the treatment of schizophrenia.

2. The use of compounds of General formula

,

where R1means aryl, unsubstituted or substituted by one or more substituents selected from the group comprising lower alkyl, (ness.)alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S - lower alkyl, -S(O)2-lower alkyl, -C(O)NR′R", -NR′R", -NR′C(O)- lower alkyl, -NR′S(O)2-lower alkyl, or means heteroaryl selected from the group comprising pyridine-2 - or-3-yl, imidazolyl or oxazolyl, unsubstituted or substituted lower alkyl, halogen or (ness.)alkoxygroup;

R2and R3independently of one another denote hydrogen, halogen, lower alkyl, (ness.)alkoxygroup, OCHF2, OCH2F, OCF3or CF3;

R4, R5independently of each lake is achut hydrogen, -(CR′R)1-(CR′R)1-(CR′R)a 0.1-OH or -(CR′R)1-(CR′R)1-(CR′R)a 0.1-lower alkyl, where R' and R" at each carbon atom may be the same or may differ from each other, -C1,2-alkyl, -C(O)H, -(CH2)about-cycloalkyl, unsubstituted or substituted by hydroxyl, -(CH2)1,2,3NR′C(O)-lower alkyl, -(CH2)1,2,3NR′S(O)2-lower alkyl or -(CH2)aboutS(O)2is lower alkyl;

R′ means hydrogen, lower alkyl, -(CH2)aboutHE, -C(O)H, -C(O)-lower alkyl, -C(O)-cycloalkyl or-S(O)2is lower alkyl;

R ' means hydrogen or lower alkyl;

or R4and R5together with the nitrogen atom to which they are linked, form a ring with -(CH2)3-5-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising lower alkyl, halogen, CF3, -(CR′R)oOH, =O, -NR′R", where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)oNR′-C(O)-lower alkyl, -(CH2)about-C(O)-lower alkyl, -(CH2)about-C(O)-cycloalkyl, (CH2)oOC(O)NR′R", -(CH2)about-S(O)2-lower alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R"; ilibrary ring with -(CH 2)1,2,3-NR′-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising lower alkyl, halogen, -(CR′R)oOH, =O, -NR′R", where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)oNR′-C(O)-lower alkyl, -(CH2)about-C(O)-lower alkyl, -(CH2)about-C(O)-cycloalkyl, (CH2)oOC(O)NR′R", -(CH2)about-S(Oh)2-lower alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R"; or form a ring with -(CH2)1,2,3-O-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising lower alkyl, halogen, -(CR′R)oOH, =O, -NR′R", where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)oNR'-C(O)-lower alkyl, -(CH2)about-C(O)-lower alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)aboutO-C(O)NR′R", -(CH2)o-S(O)2-lower alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R"; or form a ring with

-(CH2)1,2,3-S(O)0,1,2-(CH2)2-this ring is unsubstituted who passed or substituted by one or more substituents, selected from the group comprising lower alkyl, halogen, -(CR′R)oOH, =O, -NR′R", where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)oNR′-C(O)-lower alkyl, -(CH2)about-C(O)-lower alkyl, -(CH2)about-C(O)-cycloalkyl, (CH2)oOC(O)NR′R", -(CH2)about-S(O)2-lower alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R"; or form a ring with CH2CH=CH-CH2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising lower alkyl, halogen, -(CR′R)oOH, =O, -NR′R", where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5,

or substituted -(CH2)oNR′-C(O)-lower alkyl, -(CH2)about-C(O)-lower alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oO-C(O)NR′R", -(CH2)o-S(O)2-lower alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R"; o is 0, 1, 2 or 3;

or pharmaceutically active acid additive salts for the preparation of drugs for the treatment of schizophrenia.

3. The use of compounds of the formula I according to claim 1, where the connections are dual antagonist of the mi receptors NK1/NK3.

4. The use of compounds of the formula I according to claim 1 for the treatment of positive and negative symptoms of schizophrenia.

5. The use of compounds of the formula I according to claim 1, when the compounds of formula I include all stereoisomeric forms, each of the individual enantiomers and mixtures thereof.

6. The use of compounds of the formula I according to claim 1, where R1, R4and R5have given in claim 1 values and R2and R3both mean CF3.

7. The use of compounds of the formula I according to claim 1, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)3-5-, which is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)oOH, =O, -NR′R", where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)aboutNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)NR′R", -(CH2)about-S(O)2-alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R".

8. The use of compounds of the formula I according to claim 7, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)3-5-where the ring has one or two Deputy representing hydroxyl, -CH2OH or-C(O)N.

9. The use of compounds of formula I of claim 8, where the compounds are

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(5-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chloro-4-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-hydroxymethylene)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-hydroxymethylene)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(5-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chloro-4-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-guide ximetilpropan-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-hydroxymethylene)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(5-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-hydroxymethylene)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(5-fluoro-2-were)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxyethylpyrrolidine the n-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(3R,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)for 3,5-dihydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(3S,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)for 3,5-dihydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-formylpyridine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-4-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-acid)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tolyl-pyridin-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-acid)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-acid)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-acid)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-g is droxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3,5-acid)-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(deformedarse)phenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methyl-2-(3-trifloromethyl)isobutyramide and

(2S,4R)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methyl-2-(3-trifloromethyl)isobutyramide.

10. The use of compounds of the formula I according to claim 7, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)3-5-where the ring is mono - or disubstituted by groups NH2NHS(O)2CH3, NCH3S(O)2CH3N(CH2 CH3)S(O)2CH3, NHC(O)CH3and-CH2HE.

11. The use of compounds of formula I of claim 10, these connections are

(2S,4S)-N-[6-(4-acetylamino-2-hydroxyethylpyrrolidine-1-yl)-4-(2-chlorophenyl)-pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(R)-N-[6-(3-aminopyrrolidine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-{4-(4-fluoro-2-were)-6-[3-(methysulfonylmethane)pyrrolidin-1-yl]pyridine-3-yl}-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-[3-(ethylmethylamino)pyrrolidin-1-yl]-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-4-methanesulfonamido-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-4-(methysulfonylmethane)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine and

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(ethylmethanesulfonate)-4′-(4-fluoro-2-were)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine.

12. The use of compounds fo the formula I according to claim 7, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)4-where the ring has two substituent groups =O and-CH2HE.

13. The use of compounds of the formula I according to item 12, such compounds are

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxymethyl-4-oxopyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine and

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-4-oxopyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine.

14. The use of compounds of the formula I according to claim 7, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)4-where the ring is di - or tizamidine halogen and a group-CH2HE.

15. The use of compounds of formulas I through 14, such compounds are

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-fluoro-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-fluoro-2-hydroxyethylpyrrolidine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4,4-debtor-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4,4-debtor-2-hydroxyethylpyrrolidine-1-yl)-4-(4-fluoro-2-were)Piri is INF-3-yl]-N-methylisoleucine and

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-fluoro-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine.

16. The use of compounds of the formula I according to claim 7, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)3-5-where the ring is substituted by the groups CH2S(O)CH3CH2SCH3or CH2S(O)2CH3.

17. The use of compounds of the formula I according to article 16, such compounds are

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine, 2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-4-methylsulfonylmethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-4-methylisobutyl,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-4-methanesulfonamide-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-4-methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methyl-sulfonilmorpholid-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-{4-(4-fluoro-2-were)-6-[(RS)-3-((RS)-methanesulfonamide)pyrrolidin-1-yl]pyridine-3-yl}--methylisobutyl and

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine.

18. The use of compounds of the formula I according to claim 7, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)3-5-where the ring is substituted by a group S(O)2CH3, SCH3, S(O)CH3or S(O)2N(CH3)2.

19. The use of compounds of the formula I according p, such compounds are

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonamido-1-yl)pyridine-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-3-methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-4-methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-dimethylsulphamoyl-4′-(4-fluoro-2-were)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-methylsulfanyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]piperidin the l-5′ -yl]-N-methylisoleucine and

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-methanesulfonyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine.

20. The use of compounds of the formula I according to claim 1, where-NR4R5is

,,,

,,or

and R′ is the same as described in claim 1.

21. The use of compounds of the formula I according to claim 20, these compounds are

(1S,3R,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-8-azabicyclo[3.2.1]Oct-8-yl)pyridine-3-yl]-N-methylisoleucine,

(1R,3S,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-8-azabicyclo[3.2.1]Oct-8-yl)pyridine-3-yl]-N-methylisoleucine,

(rat)-(1R,3R,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonyl-8-azabicyclo[3.2.1]Oct-8-yl)pyridine-3-yl]-N-methylisoleucine,

(1R,3R,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonyl-8-azabicyclo[3.2.1]Oct-8-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1-oxa-4-thia-8-azaspiro[4.5]Dec-8-yl)feast of the DIN-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4,4-dioxo-1-oxa-4λ6-thia-8-azaspiro[4.5]Dec-8-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1-oxa-5-thia-9-azaspiro[5.5]undec-9-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(5,5-dioxo-l-oxa-5λ6-thia-9-azaspiro[5.5]undec-9-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1,1,4,4-tetraoxo-1λ6,4λ6-dithia-8 azaspiro[4.5]Dec-8-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1,1,5,5-tetraoxo-1λ6,5λ6-dithia-9 azaspiro[5.5]undec-9-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1-oxa-8-Aza-Spiro[4.5]Dec-8-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[(1S,5R)-4-(4-fluoro-2-were)-6-8-oxa-3-azabicyclo[3.2.1]Oct-3-espiridion-3-yl]-N-methylisoleucine,

(1S,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(8,8-dioxo-8λ6-thia-3-Aza-bicyclo[3.2.1]Oct-3-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(1S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-((1S,4S)-5-methanesulfonyl-2,5-diazabicyclo[2.2.1]hept-2-yl)pyridine-3-yl]-N-methyl-isobutyramide and

(1R,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(8-methanesulfonyl-3,8-diazabicyclo[3.2.1]Oct-3-yl)pyridine-3-yl]-N-methyl-isobutyramide.

22. The use of compounds of the formula I according to claim 1, where R4and R5independently of one another denote hydrogen, -(CR′R)1-(CR′R)1-(CR′R)a 0.1-OH or -(CR′R)1-(CR′R)1-(CR′R)a 0.1-alkyl, where R′ and R" at each carbon atom may be the same or may differ from each other and are as defined in claim 1, -C1,2-alkyl, -C(O)H, -(CH2)about- cycloalkyl, unsubstituted or substituted hydroxyl group, or mean -(CH2)1,2,3NR′R", -(CH2)1,2,3NR′C(O)-alkyl, -(CH2)1,2,3NR′S(O)2-alkyl, -(CH2)aboutS(O)-alkyl, -(CH)aboutS-alkyl, -(CH2)oS(O)2-alkyl or -(CH2)oS(O)2-NR′R".

23. The use of compounds of the formula I according to article 22, where R4and R5independently of one another denote hydrogen, -CH(CH2OH)CH2OH or -(CH2)1-3HE.

24. The use of compounds of the formula I according to item 23, such compounds are

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-1-hydroxymethylamino)pyridine-3-yl]-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methyl is isobutyramide,

N-{6-[bis(2-hydroxyethyl)amino]-4-o-tailpiece-3-yl}-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-4-{4-(4-fluoro-2-were)-6-[(2-hydroxyethyl)-(3-hydroxypropyl)amino]pyridine-3-yl}-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(3-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(5-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(2-bromophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-triptoreline)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-N-[6-(4-acetylamino-2-hydroxyethylpyrrolidine-1-yl)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[6-(2-hydroxyethylamino)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylene is about)pyridine-3-yl]-N-methylisoleucine and

2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxyethylamino)-pyridine-3-yl]-N-methylisoleucine.

25. The use of compounds of the formula I according to article 22, where R4and R5independently of one another denote hydrogen, (CH2)2SCH3, (CH2)2S(O)2CH3or (CH2)2S(O)2NHCH3.

26. The use of compounds of the formula I according A.25, such compounds are

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-methylsulfonylamino)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-methanesulfonamido)pyridine-3-yl]-N-methylisoleucine and 2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-methylcarbamoylmethyl-amino)pyridine-3-yl]-N-methylisoleucine.

27. The use of compounds of the formula I according to article 22, where R4and R5independently of one another denote hydrogen, (CH2)2NH2, (CH2)2NHS(O)2CH3and (CH2)2NHC(O)CH3.

28. The use of compounds of the formula I according to item 27, such compounds are

N-[6-(2-aminoethylamino)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-methanesulfonylaminoethyl)pyridine-3-yl]-N-methylisoleucine and

N-[6-(2-acetylamino the laminitis)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine.

29. The use of compounds of the formula I according to claim 5, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)1,2,3-O-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)oON, =O, -Cho, -NR′R", where R′ and R" are as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)oNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)R NR'r", -(CH2)about-S(O)2-alkyl, -(CH2)o-S(O)-alkyl, -(CH2)about-S-alkyl, -(CH2)o-S(O)2-NR′R", -(CH2)o-pyrrolidinyl or-C(O)NR′R".

30. The use of compounds of the formula I according to clause 29, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)2-O-(CH2)2-where the ring is unsubstituted or substituted by a group-CH2OH.

31. The use of compounds of the formula I according to item 30, such compounds are

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxymethylpropane-4-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-(2-(3,5-bis(thrift rmutil)phenyl)-N-[6-(3-hydroxymethylpropane-4-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxymethylimidazole-3-yl)pyridine-3-yl]-N-methylisoleucine and

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-morpholine-4-yl-pyridine-3-yl]-N-methylisoleucine.

32. The use of compounds of the formula I according to claim 5, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)1,2,3-S(O)0,1,2-(CH2)1,2,3-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)o-OH, =O, -CHO, -NR′R", where R′ and R" are as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)aboutNR'-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)NR′R", -(CH2)about-(O)2-alkyl, -(CH2)o-S(O)-alkyl, -(CH2)about-S-alkyl, -(CH2)o-S(O)2-NR′R", -(CH2)about-pyrrolidinyl or-C(O)NR′R".

33. The use of compounds of the formula I according p, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)2-S(O)2-(CH2)2-where the ring is unsubstituted what does substituted by a group-CH 2HE or stands.

34. The use of compounds of the formula I according p, where connections are

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxymethyl-1,1-dioxo-1λ6-thiomorpholine-4-yl)iridin-3-yl]-N-methyl-isobutyramide,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethyl-1,1-dioxo-1λ6-thiomorpholine-4-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-thiazolidin-3-espiridion-3-yl]-N-methylisoleucine,

(1RS,4RS)or (1RS,4SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxymethyl-1-oxo-1λ4-thiazolidin-3-yl)pyridine-3-yl]-N-methylisoleucine (diastereomeric the racemate from example 349),

(1RS,4SR)- or (1RS,4KS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxymethyl-1-oxo-1λ4-thiazolidin-3-yl)pyridine-3-yl]-N-methylisoleucine(diastereomeric the racemate from example 348),

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxymethyl-1,1-dioxo-1λ6-thiazolidin-3-yl)pyridine-3-yl]-N-methylisoleucine,

(+)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethyl-1,1-dioxo-1λ6-thiomorpholine-4-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(-)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethyl-1,1-dioxo-1λ6-thiomorpholine-4-yl)-4-o-tailpiece-3-yl]-N-meth is isobutyramide,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1-oxo-1λ4-[1,4]thiazepan-4-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(1,1-dioxo-1λ6-[1,4]thiazepan-4-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(1,1-dioxo-1λ6-[1,3]diazinon-3-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine and

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-methyl-1,1-dioxo-1λ6-[1,2,4]thiadiazine-4-Y1)pyridine-3-yl]-N-methylisoleucine.

35. The use of compounds of the formula I according to claim 1, where R1, R4and R5have given in claim 1 values and R2and R3are others, but not di-CF3.

36. The use of compounds of the formula I according p, where connections are

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3,5-dichlorophenyl)-N-methylisoleucine,

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3-fluoro-5-triptoreline)-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-methoxyphenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-dichlorophenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-dichlorophenyl)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-dichlorophenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3-fluoro-5-triptoreline)-N-methylisoleucine,

(2S,4R)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3-fluoro-5-triptoreline)-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-methoxyphenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-deformational)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-deformational)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-deformational)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-acid)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tolyl-pyridin-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-acid)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-acid)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylamino)-pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-acid)-N-[-(4-fluoro-2-were)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-acid)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3,5-acid)-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[6-(2-hydroxyethylamino)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(deformedarse)phenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylamino)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxyethylamino)-pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxymet pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methyl-2-(3-trifloromethyl)isobutyramide,

(2S,4R)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-pyridin-3-yl]-N-methyl-2-(3-trifloromethyl)isobutyramide,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-piperazine-1-espiridion-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-piperazine-1-yl-pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-methyl-N-(6-piperazine-1-yl-4-o-tailpiece-3-yl)isobutyramide and

2-(3,5-bis(deformedarse)phenyl)-N-[6-(4-methanesulfonylaminoethyl-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine.

37. The use of compounds of the formula I according to claim 5, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)1,2,3-NR′-(CH2)2-, which is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, halogen, CF3, -(CR′R)oOH, =O, -Cho, -NR′R", where R′ and R" are the SJ such as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)oNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)about-OC(O)NR′R", -(CH2)about-S(O)2-alkyl, -(CH2)about-S(O)-alkyl, -(CH2)o-S-alkyl, -(CH2)o-S(O)2-NR′R", -(CH2)about-pyrrolidinyl or-C(O)NR′R".

38. The use of compounds of the formula I according to clause 37, where R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)1,2,3-NR′-(CH2)2and where R′ when the nitrogen atom denotes hydrogen, lower alkyl, C(O)H, C(O)CH3, C(O)-cyclopropyl, S(O)2-lower alkyl, S(O)2-CH2Cl or S(O)2-N(CH3)2.

39. The use of compounds of the formula I according to 38, where the compounds are

N-[6-(4-acetylpiperidine-1-yl)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-cyclopropanecarbonyl-piperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

N-[6-(4-acetyl - [1,4]diazepan-1-yl)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(5-oxo[1,4]Diaz is pan-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonyl-imidazolidin-1-yl)pyridine-3-yl]-N-methylisoleucine, N-[6-(3-acetylimidazole-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonylaminoethyl-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-chloro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-acanaloniidae-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-chloromethanesulfonyl-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-dimethylsulfoniopropionate-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl the-3-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonyl-2-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonyl-2-methylpiperazin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-3-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonyl-3-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonyl-3-methylpiperazin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2RS,5SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2,5-dimethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,6R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2,6-dimethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(3S,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-3,5-dimethylpiperazine-1-yl)pyridine-3-yl]-N-mate is isobutyramide,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-formyl-2-hydroxyethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-cyclopropanecarbonyl-2-hydroxyethylpiperazine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(S)-N-[6-(4-acetyl-2-hydroxyethylpiperazine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-ethyl-2-hydroxyethylpiperazine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxymethyl-4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethyl-4-methanesulfonyl-piperazine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxymethyl-4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-3,3-Dimethylpiperidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonyl-3,3-d is methylpiperazin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-hydroxymethylene)-6-(4-methanesulfonyl-3-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2,2-dimethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonyl-2,2-dimethylpiperazine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-piperazine-1-espiridion-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-piperazine-1-espiridion-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-methyl-N-(6-piperazine-1-yl-4-o-tailpiece-3-yl)isobutyramide and

2-(3,5-bis(deformedarse)phenyl)-N-[6-(4-methanesulfonylaminoethyl-1-yl)-4-o-tolyl-pyridin-3-yl]-N-methylisoleucine.

40. Compounds covered by formula I as described in claim 1

where R1means phenyl, unsubstituted or substituted by one or more substituents selected from the group comprising Alki is, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R′′, -NR′R′′or denotes heteroaryl selected from the group comprising pyridine-2 - or-3-yl and oxazolyl, unsubstituted or substituted by alkyl, halogen or alkoxygroup;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3;

R4and R5mean independently from each other hydrogen, -(CR′R)1-(CR′R)1-(CR′R)a 0.1-OH or -(CR′R)1-(CR′R)1-(CR′R)a 0.1-lower alkyl, where R′ and R" at each carbon atom may be the same or may differ from each other and mean With1,2-alkyl, -C(O)H, -(CH2)0-cycloalkyl, unsubstituted or substituted by hydroxyl, -(CH2)1,2,3NR′R", -(CH2)1,2,3NR′C(O)-alkyl,

-(CH2)1,2,3NR′S(O)2-alkyl, -(CH2)oS(O)-alkyl, -(CH2)aboutS-alkyl,

-(CH2)aboutS(O)2-alkyl,

R′ means hydrogen, alkyl, -(CH2)aboutHE, -S(O)2-alkyl, -S(O)-alkyl, -S-alkyl;

R ' means hydrogen or alkyl; or

R4and R5together with the nitrogen atom to which they are linked, form a ring with -(CH2)3-5-the ring is unsubstituted or substituted by one or more substituents, selected from the group comprising alkyl, halogen, CF3, -(CR′R)oOH, =O, -Cho, -NR′R", where R′ and R" are as described above, or may together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)oNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)about-S(O)2-alkyl, -(CH2)about-S(O)-alkyl, -(CH2)o-S-alkyl, -(CH2)oS(O)2-NR′R", -(CH2)about-pyrrolidinyl or-C(O)NR′R"; or form a ring with -(CH2)1,2,3-NR′-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising -(CR′R)oOH, =O, -Cho, or substituted, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)about-S(O)2-alkyl, -(CH2)about-S(O)-alkyl, -(CH2)about-S-alkyl, -(CH2)o-S(O)2-NR′R", -(CH2)about-pyrrolidinium; or form a ring with -(CH2)1,2,3-O-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, -(CR′R)oOH; or form a ring with -(CH2)2-S(O)2N(CH3)-CH2or-SO)-O-(CH 2)2,3-; or-NR4R5is

,

,,

on means 0, 1, 2 or 3,

where connections are

N-[4-(2-chlorophenyl)-6-(2-hydroxyethylamino)pyridine-3-yl]-2-(3,5-dichlorophenyl)-N-methylisoleucine,

2-(3,5-dichlorophenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylamino)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-[(2-hydroxyethyl)methylamino]pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-[ethyl(2-hydroxyethyl)amino]pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-[(2-hydroxyethyl)propyl-amino]pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-[butyl(2-hydroxyethyl)amino]-4-(2-chlorophenyl)pyridine-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-[(2,3-dihydroxypropyl)methylamino]pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(1-hydroxymethyl-3-methylbutylamine)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylamino)pyridine-3-yl]-N-methylisobutyl the Ministry of foreign Affairs,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chloro-4-forfinal)-6-(2-hydroxyethylamino)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-dichlorophenyl)-6-(2-hydroxyethylamino)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-dichlorophenyl)-6-(2-hydroxypropylamino)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxypropylamino)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxypropylamino)pyridine-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxypropylamino)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-2-methylpropylamine)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxyethylamino)-pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxypropylamino)pyridine-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2,3-dihydroxypropyl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-1-methylethylamine)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorphen the l)-6-(2-hydroxy-1-methylethylamine)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-1-hydroxymethylamino)pyridine-3-yl]-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

N-{6-[bis(2-hydroxyethyl)amino]-4-o-tailpiece-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-[(2-hydroxyethyl)-(3-hydroxypropyl)amino]pyridine-3-yl]-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(2,4-dichlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(3,4-dichlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(4-forfinal)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-forfinal)-6-[(2-hydroxyethyl)methylamino]pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-[ethyl(2-hydroxyethyl)amino]-4-(4-forfinal)-pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-[ethyl(2-hydroxyethyl)amino]-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(cryptomite is)phenyl)-N-[6-[(2-hydroxyethyl)propylamino]-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxypropylamino)-4-o-tailpiece-3-yl]-N-methylisoleucine,

N-[6-[bis(2-hydroxypropyl)amino]-4-o-tailpiece-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2,3-dihydroxypropyl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2,3-dihydroxypropyl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

N-[6-[bis(2-hydroxypropyl)amino]-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2,3-dihydroxypropyl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2,3-dihydroxypropyl)pyridine-3-yl]-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(3-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(5-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(2-hydroxypropylamino)pyridine-3-yl]-N-methylisoleucine,

N-[6-[bis(2-hydroxyethyl)amino]-4-(2-bromophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)--(2-hydroxy-1-hydroxymethylamino)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxy-1-hydroxyethylamino)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(1R,2R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-1-hydroxymethylpropane)pyridine-3-yl]-N-methylisoleucine,

(1R,2S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-1-hydroxymethylpropane)pyridine-3-yl]-N-methylisoleucine,

(1S,2R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-1-hydroxymethylpropane)pyridine-3-yl]-N-methylisoleucine,

(1S,2S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-1-hydroxymethylpropane)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-[hexyl(2-hydroxyethyl)amino]pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-[(2-hydroxyethyl)pentyl-amino]pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-[(2-hydroxyethyl)(3-hydroxypropyl)amino]pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxypropylamino)-4-o-tolyl-pyridin-3-yl]-N-methylisoleucine or

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-[(2-hydroxy-1-hydroxymethylation)methylamino]pyridine-3-yl]-N-methylisoleucine.

41. Compounds covered by formula I as described in claim 1

where R1means phenyl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R", -NR′R;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3and

R4and R5mean independently from each other hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3or -(CH2)2NHC(O)CH3.

R′ means hydrogen, alkyl, -(CH2)aboutHE, -S(O)2-alkyl, -S(O)-alkyl, -S-alkyl;

R ' means hydrogen or alkyl;

on means 0, 1, 2, or 3.

42. The compounds of formula I according to paragraph 41, where the compounds are

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-methanesulfonamido)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-methylsulfonylamino)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-methanesulfonamido)pyridine-3-yl]-N-methylisoleucine,

N-6-(2-aminoethylamino)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-methanesulfonylaminoethyl)pyridine-3-yl]-N-methylisoleucine and

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-methylcarbamoylmethyl-amino)pyridine-3-yl]-N-methylisoleucine.

43. Compounds covered by formula I as described in claim 1

where R1means phenyl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R", -NR′R;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3;

R4means hydrogen and

R5means -(CH2)about-cycloalkyl, unsubstituted or substituted by hydroxyl;

R′ means hydrogen, alkyl, -(CH2)aboutHE, -S(O)2-alkyl, -S(O)-alkyl, -S-alkyl;

R ' means hydrogen or alkyl;

on means 0, 1, 2 or 3;

such compounds are

TRANS-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxycyclohexanone)pyridine-3-yl]-N-methylisoleucine,

TRANS-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-dichlorophenyl)-6-(4-hydroxy-cyclohexylamino)p is ridin-3-yl]-N-methylisoleucine,

TRANS-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxycyclohexanone)pyridine-3-yl]-N-methylisoleucine,

TRANS-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(4-hydroxycyclohexanone)pyridine-3-yl]-N-methylisoleucine,

(1RS,2RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-cyclohexylamino)pyridine-3-yl]-N-methylisoleucine,

(1R,2R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-cyclopentylamine)pyridine-3-yl]-N-methylisoleucine,

(1S,2S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxy-cyclopentylamine)pyridine-3-yl]-N-methylisoleucine or

(1S,2S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxycyclophosphamide)pyridine-3-yl]-N-methylisoleucine.

44. Compounds covered by formula I as described in claim 1

where R1means phenyl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R", -NR′R;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3and

R4and R5form together with the nitrogen atom, to the which they are attached, a ring with -(CH2)3-5-, which is unsubstituted or substituted by one or more substituents selected from the group comprising -(CR′R)o-OH;

R′ means hydrogen, alkyl, -(CH2)aboutHE, -S(O)2-alkyl, -S(O)-alkyl, -S-alkyl;

R ' means hydrogen or alkyl;

on means 0, 1, 2 or 3;

such compounds are

(S)-N-[4-(2-chlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3,5-dichlorophenyl)-N-methylisoleucine,

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3,5-dichlorophenyl)-N-methylisoleucine,

(S)-N-[4-(2-chlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3-fluoro-5-triptoreline)-N-methylisoleucine,

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3-fluoro-5-triptoreline)-N-methylisoleucine,

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3,5-differenl)-N-methylisoleucine,

(S)-2-(3-chloro-5-methoxyphenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-methoxyphenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-N-[4-(2-chlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3,5-dimethyl who enyl)-N-methylisoleucine,

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3, 5dimethylphenyl)-N-methylisoleucine,

(S)-2-(3,5-dichlorophenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-dichlorophenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-1-yl)-4-o-tolyl-pyridin-3-yl]-N-methylisoleucine,

(S)-2-(3-fluoro-5-triptoreline)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2R,4S)-2-(3-fluoro-5-triptoreline)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-differenl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-differenl)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3-chloro-5-methoxyphenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-methoxyphenyl)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3, 5dimethylphenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3, 5dimethylphenyl)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-dichlorophenyl)-N-[4-(4-fluoro-2-were-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-dichlorophenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3-fluoro-5-triptoreline)-N-methylisoleucine,

(2S,4R)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3-fluoro-5-triptoreline)-N-methylisoleucine,

(S)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methyl-2-(3-triptoreline)isobutyramide,

(2S,4R)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methyl-2-(3-triptoreline)isobutyramide,

(S)-2-(3,5-differenl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-differenl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3-chloro-5-methoxyphenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-methoxyphenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-(3, 5dimethylphenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3, 5dimethylphenyl)-N-[4(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3-chloro-5-deformational)-N-[4-(2-chlorophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-deformational)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3-chloro-5-deformational)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-deformational)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3-chloro-5-deformational)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3-chloro-5-deformational)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-N-[6-(4-acetylamino-2-hydroxyethylpyrrolidine-1-yl)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3-hydroxypyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-4-(2-chlorophenyl)-6-(3-hydroxypyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(3R,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3,4-dihydroxy-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(3R,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3,4-dihydroxy-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-dichlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3,4-dichlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxypyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-br is fenil)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3,4-dichlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-dichlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-dichlorophenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-(4-(4-fluoro-2-were)-6-[2-(1-hydroxy-1-METI is ethyl)pyrrolidin-1-yl]pyridine-3-yl}-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(5-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(3S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3,4-dihydroxy-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(3S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3,4-dihydroxypyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(3R,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3,4-dihydroxypyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2R,5S)-N-[6-(2,5-bis(hydroxymethyl)pyrrolidin-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(2S,5S)-N-[6-(2,5-bis(hydroxymethyl)pyrrolidin-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(2R,5R)-N-[6-(2,5-bis(hydroxymethyl)pyrrolidin-1-yl)-4-(4-fluoro-2-METI is phenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-p-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-vinylpyridin-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-dimethylaminophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-bromophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3,5-differenl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R-)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3,4-differenl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridin-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-4-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-3-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-chloro-4-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-N-[4-(2-AMINOPHENYL)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-pyridin-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-methoxyphenyl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-hydroxyphenyl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-methylsulfinylphenyl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-methanesulfonyl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-[5-{[2-(3,5-bis(trifluoromethyl)phenyl)-2-methylpropionyl]m is thylamino}-2-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-4-yl]benzamide,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-differenl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chloro-4-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-formylphenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-hydroxymethylene)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-formylphenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-hydroxymethylene)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,5-dichlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(5-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,3-di is lorgeril)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chloro-4-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-dichlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-differenl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-formylphenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-hydroxymethylene)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-triptoreline)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydrox the methyl-pyrrolidin-1-yl)-4-(2-methoxyphenyl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-tianfeng)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-vinylpyridin-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-3-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-methylisobutyl,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(5-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-forfinal)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3,4-dichlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,3-dichlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-that is espiridion-3-yl]-N-methylisoleucine,

(2R,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-triptoreline)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-(2-methoxyphenyl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-forfinal)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-vinylpyridin-3-yl]-methylisobutyl,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-forfinal)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-p-tailered the n-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3,4-Dichlorophenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-chlorophenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,5-dichlorophenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,3-dichlorophenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chloro-4-forfinal)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-formylphenyl)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-hydroxymethylene)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(5-fluoro-2-were)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,5-differeni is)-6-(3-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-(2-methoxyphenyl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-bromophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-forfinal)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,4-dichlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,5-dichlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2,3-dichlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3,4-dichlorophenyl)-6-(2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-chlorophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-forfinal)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-phenylpyridine-3-and the]-N-methylisoleucine,

(3R,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)for 3,5-dihydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(3S,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)for 3,5-dihydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(4-fluoro-2-were)-4-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-acid)-N-[6-(2-hydroxyethylpyrrolidine-1-yl)-4-o-tolyl-pyridin-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-acid)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-acid)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-acid)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-2-(3,5-acid)-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[6-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(2-hydroxymethyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-N-[6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methyl-2-(3-trifloromethyl)isobutyramide and

(2S,4R)-N-[4-(4-fluoro-2-were)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-pyridin-3-yl]-N-methyl-2-(3-trifloromethyl)isobutyramide.

45. Compounds covered by formula I as described in claim 1

where R1means phenyl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R", -NR′R;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3and

R4and R5/sup> form together with the nitrogen atom to which they are attached a ring with -(CH2)3-5-, which is unsubstituted or substituted by one or more substituents selected from the group comprising-NR′R;

R′ means hydrogen, alkyl, -(CH2)aboutHE, -S(O)2-alkyl, -S(O)-alkyl, -S-alkyl;

R ' means hydrogen or alkyl;

on means 0, 1, 2 or 3;

such compounds are selected from the group including

(2S,4S)-N-[6-(4-acetylamino-2-hydroxyethylpyrrolidine-1-yl)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-N-[6-(3-acetylpyrrolidine-1-yl)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(R)-N-[6-(3-acetylpyrrolidine-1-yl)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(RS)-N-[6-[3-(acetylamino)pyrrolidin-1-yl]-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(2-pyrrolidin-1-iletilenlerin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3-dimethylamino-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3-methanesulfonyl-pyrrolidin-1-yl)pyridine-3-yl]-N-methylisobutyl is on,

(S)-N-[6-(3-acetylpyrrolidine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(R)-N-[6-(3-acetylpyrrolidine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(R)-N-[6-[3-(acetylecholine)pyrrolidin-1-yl]-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(R)-N-[6-[3-(acetylamino)pyrrolidin-1-yl]-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-N-[6-(3-aminopyrrolidine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-S-{4-(4-fluoro-2-were)-6-[3-(methysulfonylmethane)pyrrolidin-1-yl]pyridine-3-yl}-N-methylisoleucine,

(S)-(2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-[3-(ethylmethylamino)pyrrolidin-1-yl]-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(S)-N-[6-[3-(acetylecholine)pyrrolidin-1-yl]-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-N-[6-[3-(acetylamino)pyrrolidin-1-yl]-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,/p>

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-oxopyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-N-[6-(3-acetylpyrrolidine-1-yl)-4-(2-bromophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxymethyl-4-oxopyrrolidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-4-oxopyrrolidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-fluoro-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-fluoro-2-hydroxyethylpyrrolidine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4,4-debtor-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4,4-debtor-2-hydroxyethylpyrrolidine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-fluoro-2-hydroxyethylpyrrolidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-N-[6-[2-(acetamidomethyl)pyrrolidin-1-yl]-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine or

1-[5-{[2-(3,5-bis(trifluoromethyl)phenyl)2-methylpropionyl]methylamino}-4-(4-fluoro-2-were)pyridine-2-yl]pyrrolidin-2-ymetray ether (S)-dimethylcarbinol acid,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-3-hydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-hydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-2-(2-hydroxyethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(3-hydroxyazetidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

N-[4-amino-4′-(2-chlorophenyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-methanesulfonamido-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

N-[4-acetylamino-4′-(4-fluoro-2-were)-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-2-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-2-guide oximeter-3,4,5,6-tetrahydro-2H-[1,2′ ]bipyridinyl-5′-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-2-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′] bipyridinyl-5′-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxyazetidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxyazetidine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-(4-hydroxymethyl-4′-o-tolyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-N-methylisoleucine,

(3R,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-(3,5-dihydroxy-4′-o-tolyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-N-methylisoleucine,

(3R,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)for 3,5-dihydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(3S,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)for 3,5-dihydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(3RS,4SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-(3,4-dihydroxy-4′-o-tolyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-N-methylisoleucine,

(3RS,4RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-(3,4-dihydroxy-4′-o-tolyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-N-methylisoleucine,

(3RS,4SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-x is arvanil)-3,4-dihydroxy-3,4,5,6-tetrahydro-2H-[1,2′ ]bipyridinyl-5′-yl]-N-methylisoleucine,

(3RS,4RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-3,4-dihydroxy-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(2RS,4SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-hydroxy-2-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(2RS,4SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-(4-hydroxy-2-hydroxymethyl-4′-o-tolyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-N-methylisoleucine,

(3RS,4SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-(4-hydroxy-3-hydroxymethyl-4′-o-tolyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-N-methylisoleucine,

(3RS,4RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-(4-hydroxy-3-hydroxymethyl-4′-o-tolyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl)-N-methylisoleucine,

(3RS,4SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-hydroxy-3-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine,

(3RS,4RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-4-hydroxy-3-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine or

(2RS,3RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4′-(2-chlorophenyl)-3-hydroxy-2-hydroxymethyl-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-yl]-N-methylisoleucine.

46. Connection, presence covers the s by the formula I, as described in item 1

where R1means phenyl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R", -NR′R;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3;

R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)1,2,3-NR′-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising -(CR′R)oOH, =O, where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)aboutNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)about-S(O)2-alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R;

R′ means hydrogen, alkyl, -(CH2)aboutHE, -S(O)2-alkyl, -S(O)-alkyl, -S-alkyl;

R ' means hydrogen or alkyl;

on means 0, 1, 2 or 3;

such compounds are

N-[6-(4-acetylpiperidine-1-the l)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-cyclopropanecarbonyl-piperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

N-[6-(4-acetyl - [1,4]diazepan-1-yl)-4-(2-chlorophenyl)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(5-oxo[1,4]diazepan-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonamido-1-yl)pyridine-3-yl]-N-methylisoleucine,

N-[6-(3-acetylimidazole-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonylaminoethyl-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-chloro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3-fluoro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-acanaloniidae-1-yl)-4-(4-fluoro-2-were)pyridine-3-the l]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-chloromethanesulfonyl-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-dimethylsulfoniopropionate-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-3-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonyl-2-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonyl-2-methylpiperazin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-3-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonyl-3-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonyl-3-methylpiperazin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2RS,SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2,5-dimethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,6R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2,6-dimethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(3S,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-3,5-dimethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-formyl-2-hydroxyethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-cyclopropanecarbonyl-2-hydroxyethylpiperazine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(S)-N-[6-(4-acetyl-2-hydroxyethylpiperazine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-ethyl-2-hydroxyethylpiperazine-1-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxymethyl-4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethyl-4-methanesulfonyl-piperazine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-methylpheni is)-6-(3-hydroxymethyl-4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-3,3-dimethylpiperidin-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonyl-3,3-dimethylpiperidin-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(2-hydroxymethylene)-6-(4-methanesulfonyl-3-methylpiperazin-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonyl-2,2-dimethylpiperazine-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4-methanesulfonyl-2,2-dimethylpiperazine-1-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-piperazine-1-espiridion-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-piperazine-1-espiridion-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(2-chlorophenyl)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-methanesulfonylaminoethyl-1-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(deformedarse)phenyl)-N-methyl-N-(6-piperazine-1-yl-4-o-tailpiece-3-yl)isobutyramide or

2-(3,5-bis(deformedarse)phenyl)-N-[6-(4-methanesulfonylaminoethyl-1-yl)-4-o-tailpiece-3-yl]-N-m is telecomuting.

47. Compounds covered by formula I as described in claim 1

where R1means phenyl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R", -NR′R", or means heteroaryl selected from the group comprising pyridine-2 - or-3-yl and oxazolyl, unsubstituted or substituted by alkyl, halogen or alkoxygroup;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3; and

R4and R5form together with the nitrogen atom to which they are attached a ring with -(CH2)1,2,3-O-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group comprising lower alkyl, -(CR′R)oOH, =O, where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)oNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl -(CH2)about-C(O)-cycloalkyl, -(CH2)about-S(O)2-alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R;

R′ means hydrogen, al the sludge, -(CH2)aboutHE, -S(O)2-alkyl, -S(O)-alkyl, -S-alkyl;

R ' means hydrogen or alkyl;

on means 0, 1, 2 or 3;

such compounds are

(R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxymethylpropane-4-yl)pyridine-3-yl]-N-methylisoleucine,

(R)-(2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethylpropane-4-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(2-hydroxymethylpropane-4-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxymethylimidazole-3-yl)pyridine-3-yl]-N-methylisoleucine or

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-morpholine-4-yl-pyridine-3-yl]-N-methylisoleucine.

48. Compounds covered by formula I as described in claim 1

where R1means phenyl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R", -NR′R;

R2and R3mean independently from each other hydrogen, halogen, alkyl,alkoxygroup, OCHF2, OCH2F, OCF3or CF3; and

R4and R5form together with the nitrogen atom, to which they are attached a ring with -(CH2)1,2,3-S(O)0,1,2-(CH2)2-this ring is unsubstituted or substituted by one or more substituents selected from the group including

lower alkyl, halogen, -(CR′R)oOH, =O, -NR′R", where R′ and R" can together with the nitrogen atom to which they are attached, form a ring with -(CH2)3-5or substituted -(CH2)aboutNR′-C(O)-alkyl, -(CH2)about-C(O)-alkyl, -(CH2)about-C(O)-cycloalkyl, -(CH2)oOC(O)NR′R", -(CH2)about-S(O)2-alkyl, -(CH2)about-pyrrolidinyl or-C(O)NR′R;

R′ means hydrogen, alkyl, -(CH2)aboutHE, -C(O)H, -C(O)-alkyl, -C(O)-cycloalkyl, -S(O)2-alkyl, -S(O)2-halogen-alkyl, -S(O)-alkyl, -S-alkyl or-S(O)2N-dialkyl;

R ' means hydrogen or alkyl;

on means 0, 1, 2 or 3;

such compounds are

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxymethyl-1,1-dioxo-1λ6-thiomorpholine-4-yl)pyridine-3-yl]-N-methyl-isobutyramide,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethyl-1,1-dioxo-1λ6-thiomorpholine-4-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-thiazolidin-3-espiridion-3-yl]-N-methylisobutyl is rapid,

(1RS,4RS)or(1RS,4SR)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxymethyl-1-oxo-1λ4-thiazolidin-3-yl)iridin-3-yl]-N-methyl-isobutyramide (diastereomeric the racemate from example 349),

(1RS,4SR)-or(1RS,4RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-methyl-phenyl)-6-(4-hydroxymethyl-1-oxo-1λ4-thiazolidin-3-yl)pyridine-3-yl]-N-methyl-isobutyramide (diastereomeric the racemate from example 348),

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(4-hydroxymethyl-1,1-dioxo-1λ6-thiazolidin-3-yl)pyridine-3-yl]-N-methylisoleucine,

(+)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethyl-1,1-dioxo-1λ6-thiomorpholine-4-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(-)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(3-hydroxymethyl-1,1-dioxo-1λ6-thiomorpholine-4-yl)-4-o-tailpiece-3-yl]-N-methylisoleucine,

(RS)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1-oxo-1λ4-[1,4]thiazepan-4-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(1,1-dioxo-1λ6-[1,4]thiazepan-4-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine or

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(1,1-dioxo-1λ6-[1,3]diazinon-3-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine.

49. The compounds of formula I as described in claim 1, where R1means nezamedin the th or substituted phenyl, as described above, and R4and R5form together with the nitrogen atom to which they are attached, a ring-CH2CH=CH-CH2-, which is unsubstituted or substituted by one Deputy(CR′R)oOH, such a connection is selected from a group including

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(2-hydroxymethyl-2,5-dihydropyrrol-1-yl)pyridine-3-yl]-N-methylisoleucine.

50. The compounds of formula I as described in claim 1

where R1means heteroaryl selected from the group comprising pyridine-2-or-3-yl and oxazolyl, unsubstituted or substituted by alkyl, halogen or alkoxygroup;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3;

and the other substituents are as described in formula I in claim 1.

51. Compounds according to item 50, such compounds are

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(3,5-dimethylisoxazol-4-yl)-6-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6′-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-2,6-dimethoxy[3,4′]bipyridinyl-3′-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[2-chloro-6′-(4-hydroxy-2-g is proximitydisposition-1-yl)-[3,4′ ]bipyridinyl-3′-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6′-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-2-methyl - [3,4′]bipyridinyl-3′-yl]-N-methylisoleucine,

(2S,4R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[3-chloro-6′-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-[2,4′] bipyridinyl-3′-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[2-chloro-6′-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-[3,4′]bipyridinyl-3′-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6′-(4-hydroxy-2-hydroxymethyl-pyrrolidin-1-Y1)-2-methyl - [3,4′]bipyridinyl-3′-yl]-N-methylisoleucine,

(2S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[3-chloro-6′-(4-hydroxy-2-hydroxyethylpyrrolidine-1-yl)-[2,4′]bipyridinyl-3′-yl]-N-methylisoleucine,

(2R,3S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6′-(3-hydroxy-2-hydroxymethyl-pyrrolidin-1-yl)-2-methyl - [3,4′]bipyridinyl-3′-yl]-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6′-(2-hydroxyethylpyrrolidine-1-yl)-2-methyl - [3,4′]bipyridinyl-3′-yl]-N-methylisoleucine,

N-{6′-[bis(2-hydroxyethyl)amino]-2-methyl - [3,4′]bipyridinyl-3′-yl}-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine,

(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6′-(2-hydroxyethylpyrrolidine-1-yl)-4-methyl - [3,4′]bipyridinyl-3′yl]-N-methylisoleucine,

N-{6′-[bis((2-hydroxyethyl)amino]-4-methyl - [3,4′]bipyridinyl-3′-yl}-2-(3,5-bis(trifluoromethyl)phenyl)-N-methylisoleucine or

2-(3,5-bis(trifluoromethyl)phenyl)-N-{6′-[(2-hydroxyethyl)methylamino]-4-methyl-[3,4′]bipyridinyl-3′-yl}-N-methylisoleucine.

52. The compounds of formula I according to claim 1

where R1means aryl, unsubstituted or substituted by one or more substituents selected from the group comprising alkyl, alkoxygroup, halogen, -(CH2)aboutHE, -C(O)N, CF3CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR′R", -NR′R", or means heteroaryl selected from the group comprising pyridine-2 - or-3-yl and oxazolyl, unsubstituted or substituted by alkyl, halogen or alkoxygroup;

R2and R3mean independently from each other hydrogen, halogen, alkyl, alkoxygroup, OCHF2, OCH2F, OCF3or CF3;

and-NR4R5present

,

,or

or R′ means hydrogen, alkyl, -(CH2)aboutHE,- S(O)2-alkyl, -S(O)-alkyl, -S-alkyl,

R ' means hydrogen or alkyl;

on means 0, 1, 2, or 3.

53. Connect the deposits according to paragraph 52, where connections are present (1S,3R,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-8-azabicyclo[3.2.1]Oct-8-yl)pyridine-3-yl]-N-methylisoleucine,

(1R,3S,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-hydroxy-8-azabicyclo[3.2.1]Oct-8-yl)pyridine-3-yl]-N-methylisoleucine,

(rat)-(1R,3S,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonyl-8-azabicyclo[3.2.1]Oct-8-yl)pyridine-3-yl]-N-methylisoleucine,

(1R,3R,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(3-methanesulfonyl-8-azabicyclo[3.2.1]Oct-8-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1-oxa-4-thia-8-azaspiro[4.5]Dec-8-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(4,4-dioxo-1-oxa-4λ6-thia-8-azaspiro[4.5]Dec-8-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1-oxa-5-thia-9-azaspiro[5.5]undec-9-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(5,5-dioxo-1-oxa-5λ6-thia-9-azaspiro[5.5]undec-9-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1,1,4,4-tetraoxo-1λ6,4λ6-dithia-8 azaspiro[4.5]Dec-8-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(what riformati)phenyl)-N-[4-(4-fluoro-2-were)-6-(1,1,5,5-tetraoxo-1λ 6,5λ6-dithia-9 azaspiro[5.5]undec-9-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(1-oxa-8-Aza-Spiro[4.5]Dec-8-yl)pyridine-3-yl]-N-methylisoleucine,

2-(3,5-bis(trifluoromethyl)phenyl)-N-[(1S,5R)-4-(4-fluoro-2-were)-6-8-oxa-3-azabicyclo[3.2.1]Oct-3-espiridion-3-yl]-N-methylisoleucine,

(1S,5R)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[6-(8,8-dioxo-8λ6-thia-3-Aza-bicyclo[3.2.1]Oct-3-yl)-4-(4-fluoro-2-were)pyridine-3-yl]-N-methylisoleucine,

(1S,4S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-((1S,4S)-5-methanesulfonyl-2,5-diazabicyclo[2.2.1]hept-2-yl)pyridine-3-yl]-N-methylisoleucine and

(1R,5S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-were)-6-(8-methanesulfonyl-3,8-diazabicyclo[3.2.1]Oct-3-yl)pyridine-3-yl]-N-methyl-isobutyramide.

54. Drug for the treatment of schizophrenia, containing the compound as defined in any of p-53, and pharmaceutically acceptable excipients.

55. Medicinal product by item 54 for treating positive and negative symptoms in schizophrenia.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention pertains to new layers of acidic compounds with Formula I , where R2 is C1-6alkyl (possibly substituted and/or ending with one or more substitute, chosen from -OH, halogen, cyano, nitro and aryl) or aryl, where each aryl group, if not specifically mentioned, is possibly substituted by one or more substitutes, including -OH, cyano, halogen, nitro, C1-6alkyl, C1-6alkoxy, -N(R14a)R14b, -C(O)R14c, -C(O)OR14d, -C(O)N(R14e)R14f, -N(R14g)C(O)R14h, -N(R14m)S(O)2R13b, -S(O)2Rl3c and/or -OS(O)2R13d, where radicals from R13b to Rl3d independently represent C1-6alkyl; R14a and R14b independently represent H, C1-6alkyl, or jointly represent C3-6alkene, as a result, yielding a four-heptatomic nitrogen containing ring; radicals from R14c to R14m independently represent H or C1-6alkyl; A represents , where R16 represents unsubstituted C1-4alkyl, C1-4perfluoroalyl or phenyl, where the last group can be substituted with one or more substitutes, chosen from C1-6alkyl, halogen, nitro and C1-6alkoxy. The invention also relates to the method of obtaining Formula II compounds.

EFFECT: obtaining of new intermediate compounds and their use in special obtaining of formula II oxabispidin compounds, which can be used in the treatment of cardiac arrhythmia.

8 cl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a novel solid formulation of anti-arrhythmic medicinal agents. Invention describes crystalline formulation of 4-({3-[7-(3,3-dimethyl-2-oxobutyl)-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl]propyl}amino)-benznitrile, tert.-butyl-2-{7-[3-(4-cyanoanilino)propyl]-9-oxa-3,7-dizabicyclo[3.3.1]non-3-yl}ethylcarbamate, tert.-butyl-2-{7-[4-(4-cyanophenyl)butyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethylcarbamate or tert.-butyl-2-{7-[(25)-3-(4-cyanophenoxy)-2-hydroxypropyl]-9-oxa-3,7-diazabicyclo[3.3.1]non-3-yl}ethylcarbamate and their pharmaceutically acceptable salts. Also, invention describes methods for their synthesis, a pharmaceutical preparation based on thereof, a method for prophylaxis or treatment of arrhythmia and their using.

EFFECT: valuable medicinal properties of compounds and pharmaceutical preparation.

73 cl, 22 dwg, 22 tbl, 23 ex

FIELD: organic chemistry, antibiotics, chemical technology.

SUBSTANCE: invention relates to the improved method for preparing 3-aminorifampicin-S representing semi-product in synthesis of anzamycine antibiotics, such as rifabutin - an anti-tuberculosis antibiotic with prolonged effect. Invention describes a method for preparing3-aminorifampicin-S that involves interaction of 3-bromorifampicin-S with hexamethylenetetramine in the amount 2-6-fold molar excess of hexamethylenetetramine with respect to 3-bromorifampicin-S at temperature 40-65°C in organic solvent medium and isolation of the end product. Trichloroethylene is used as a solvent in preparing 3-aminorifampicin-S followed by its change for butyl acetate by addition of butyl acetate to reaction mass in the amount 2-5-fold excess with respect to trichloroethylene volume followed by distilling off trichloroethylene. Prepared 3-aminorifampicin-S butyl acetate solution is filtered through aluminum oxide layer and 3-aminorifmapicin-S is isolated by evaporation until dry. Also, invention describes variant of method for preparing 3-aminorifampicin-S. Invention provides reducing reaction time in preparing the end product, reduced cost and simplified reaction, enhanced yield and purity of the end product.

EFFECT: improved method for preparing.

2 cl, 2 tbl, 20 ex

FIELD: organic chemistry, chemical technology, antibiotics.

SUBSTANCE: invention relates to methods for preparing derivatives of 3-aazidorifamycin S eliciting antibiotic properties. Method for preparing 3-azido-derivatives of rifamycin S involves interaction rifamycin S derivative with hydrazoic acid salt in solvent medium by stirring reagents at temperature from 0oC to 100oC for 0.5-2 h followed by extraction of the end product. 3-Halogen-derivative of rifamycin S is used as rifamycin S derivative. Simple aliphatic alcohols with carbon atom number from 1 to 5 or acetonitrile, or mixture of water and organic solvent not mixing with water taken among the series: ethyl acetate, methyl acetate, benzene or its mono- or dimethyl analogues, chlorinated hydrocarbons with carbon atom number from 1 to 3 is used as a solvent. Sodium azide or potassium azide is used as hydrazoilc acid salt. Extraction of the end product is carried out by extraction with solvent not mixing with water or by dilution of reaction mixture with water followed by filtration. The claimed method provides enhancing the yield of the end product by 63-71% and to simplify the process of it isolating. Invention provides the enhancement of effectiveness of method for preparing 3-azido-derivatives of rifamycin S due to elevating yield of the end product and simplifying the process of its isolating.

EFFECT: improved preparing method.

1 tbl, 13 ex

FIELD: organic chemistry, chemical technology, antibiotics.

SUBSTANCE: invention relates to a method for preparing derivatives of 3-aminorifamycin S of the formula (I) , eliciting antibiotic properties wherein X means NH2; Y = Z and mean hydrogen atom (H) or (CH3)2C<, or C6H5CH<, or C6H10<. Method for preparing 3-amino-derivatives of rifamycin S involves stirring 3-halogen-derivative of rifamycin S in solvent medium wherein solvent represents simple aliphatic alcohols with carbon atom number from 1 to 5 or acetonitrile, or mixture of water and organic solvent not mixing with water taken among the following series: ethyl acetate, methyl acetate, benzene or its mono- or dimethyl analogues, chlorinated hydrocarbons with carbon atom number from 1 to 3 with hydrazoic acid salt wherein sodium azide is used and stirring is carried out for 0.5-2 h. Then method involves the following conversion of obtained 30azido-derivative of rifamycin S to the end product using a reducing agent wherein mixture of zinc or iron with acetic acid is used, or hydrogen in the presence of palladium catalyst followed by treatment with oxidizing agent wherein ferric (III) chloride or manganese (IV) oxide is used, or hydrogen peroxide, or persulfates, or air. Extraction of the end product is carried out by extraction with organic solvent not mixing with water or by dilution of reaction mixture with water followed by crystallization of product. Invention provides the enhancement of method for preparing 3-amino-derivatives of rifamycin S due to elevating yield of the end product and process for it isolating.

EFFECT: improved preparing method.

1 tbl, 4 ex

The invention relates to a derivative phthalazine General formula (I) or their pharmaceutically acceptable salts, or hydrates, where R1and R2are the same or different from each other and each represents a halogen atom, a C1-C4alkyl group which may be substituted by a halogen atom, a hydroxyl group or a C1-C4alkoxygroup, which may be substituted by a halogen atom, or cyano; X represents a cyano, a halogen atom, hydroxyimino, optional O-substituted C1-C4alkyl group, or a heteroaryl group selected from thiazoline, thienyl, pyrazolidine, triazolinones and tetrazolyl groups that may be substituted WITH1-C4alkyl group; Y represents a cyclic amino group (i) - (v) described in paragraph 1 of the claims; (vi) etinilnoy or ethyl group substituted WITH1-C4alkyl group, which, in turn, replaced by a number of deputies referred to in paragraph 1 of the claims; (vii) optionally substituted phenyl group; (viii) pyridyloxy or thiazolidine group

The invention relates to new compounds rifamitinov series formula:

< / BR>
A new connection can be used as an antibacterial and antituberculosis drug

The invention relates to the field of organic chemistry, namely, the method of production of functionally substituted fullerenes, which can be used as complexing agents, sorbents, biologically active compounds

The invention relates to organic chemistry, in particular to a method of obtaining functionally substituted fullerenes, which can be used as complexing agents, sorbents, biologically active compounds

The invention relates to the field of organic chemistry, namely, the method of production of functionally substituted fullerenes, which can be used as complexing agents, sorbents, biologically active compounds

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

The invention relates to new spirochetes formula I

< / BR>
where 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 pharmaceutically acceptable salts

The invention relates to salts sulfoxides derived, namely the hydrochloride or the fumarate of 1-{ 2-[(2R)-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholine-2-yl] ethyl} Spiro[benzo(C)thiophene-1(3H),4'-piperidine]-(2S)-oxide, which have a good absorption when taken orally and demonstrate excellent antagonistic activity as receptor NK1and receptor NK2

The invention relates to new derivatives of pyrrolidinone possessing biological activity, in particular derivatives of 1H-3-aryl-pyrrolidin-2,4-dione

FIELD: chemistry.

SUBSTANCE: invention pertains to new compounds with general formula: , where R is -(CH2)n-A, where A: where each of B and C independently represent phenyl or phenyl substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, -OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NH-C(O)-(C1-C6alkyl) and -NO2; or n equals an integer from 0 to 3; n1 equals an integer from 1 to 3; n2 equals an integer from 0 to 4; n3 equals an integer from 0 to 3; n4 equals an integer from 0 to 2; X1 is chosen from a chemical bond -S-, -S(O)2-, -NH-, -NHC(O)- and -C=C-, R1 is chosen from C1-C6alkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, tetrahydropyranyl, CN, -N(C1-C6alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, naphtyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolydinyl, thiomopholinyl, tetrazolyl, benzoxazolyl, imidazolidine-2-thionyl, 7,7-dimethylbicyclo[2.2.1]heptane-2-onyl, benzo[1.2.5]oxadiazolyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and pyrrolyl, each of which can be optionally substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NO2, -SO2(C1-C3alkyl), -SO2NH2, -SO2N(C1-C3alkyl)2, -COOH, -CH2-COOH, pyridyl, 2-methylazolyl, morpholino, 1-chloro-2-methylpropyl, phenyl, (optionally substituted with one or more halogens), benzyloxy, and , X2 selected from -O-, -CH2-, -S-, -SO-, -SO2-, -NH- and , R2 represents a ring group, chosen from a phenyl or thienyl group. Each ring group is substituted with a group with formula -(CH2)n4-CO2H; and besides that, the ring group can optionally be substituted with 1 or 2 extra substitutes, independently chosen from halogen, - C1-C6alkyl and -C1-C6alkoxy; R3 is chosen from H, halogen and -NO2; R4 is chosen from H, halogen and morpholino; or its salt form, used in pharmaceuticals. The invention also relates to pharmaceutical compositions, to methods of treatment, and to compounds with formula (A).

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on them, which have inhibiting effect on cytosolic phospholipase A2.

45 cl, 300 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

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