RU2001101429A

RU2001101429A - IMIDAZOLYL DERIVATIVES

Info

Publication number: RU2001101429A
Application number: RU2001101429/04A
Authority: RU
Inventors: Кристоф Алан ТЮРИО; Лиди Франсин ПУАТУ; Мари-Одиль ГАЛЬСЕРА; Томас Д. Гордон; Барри МОРГАН; Кристоф Филипп МУАНЕ
Original assignee: Сосьете Де Консей Де Решерш Э Д`Аппликасьон Сьентифик Сас
Priority date: 1998-06-12
Filing date: 1999-06-08
Publication date: 2003-03-27

Claims

1. The compound of formula (I)

racemic-diastereomeric mixtures and optical isomers of the compound represented by formula (I), pharmaceutically acceptable salts and their prodrugs or their pharmaceutically acceptable salts, where ----- is an optional bond;
R ¹ represents H, - (CH ₂ ) _m —C (O) - (CH ₂ ) _m —Z ¹ , - (CH ₂ ) _m — _Z ¹ , - (CH ₂ ) _m —OZ ^1, or - (C ₀ -C ₆ ) alkyl-C (O) -NH- (CH ₂ ) _m -Z ³ ;
Z ¹ is an optionally substituted radical selected from the group consisting of (C ₁ -C ₁₂ ) alkyl, benzo [b] thiophene, phenyl, naphthyl, benzo (b] furanyl, thiophene,

isoxazolyl, indolyl,
R ² represents H or (C ₁ -C ₆ ) alkyl; or R ¹ and R ² combine together with the nitrogen atoms to which they are attached to form a compound represented by the formula (la), (Ib) or (1c),

R ³ represents - (CH ₂ ) _m —E— (CH ₂ ) _m —Z ² ;
E represents O, S, —C (O) -, —C (O) —O—, —NH — C (O) —O — or a bond;
Z ² represents H, (C ₁ -C ₁₂ ) alkyl, amino, (C ₁ -C ₁₂ ) alkylamino, N, N-di- (C ₁ -C ₁₂ ) alkylamino, (C ₁ -C ₁₂ ) alkylguanidino or an optionally substituted radical selected from the group consisting of phenyl, indolyl, imidazolyl, thiophene, benzothiophene, pyridinyl and naphthyl;
R ⁴ represents H or - (CH ₂ ) _m —A ¹ ;
And ¹ represents —C (═Y) —N (X ¹ X ² ), —C (═Y) —X ² , C (= NH) —X ² or X ² ;
Y represents O or S;
X ¹ represents H, (C ₁ -C ₁₂ ) alkyl, - (CH ₂ ) _m -NH- (C ₁ -C ₆ ) alkyl, - (CH ₂ ) _m -N-di- (C ₁ -C ₆ ) alkyl or - (CH ₂ ) _m -aryl;
X ² represents - (CH ₂ ) _m —Y ¹ X ³ or optionally substituted (C ₁ -C ₁₂ ) alkyl;
Y ¹ represents O, S, NH, C = O, (C ₂ -C ₁₂ ) alkenyl containing one or more double bonds, -NH-CO-, -CO-NH-, -NH-CO-O- ( CH ₂ ) _m -, -C≡C-, SO ₂ or a bond;
X ³ represents H, an optionally substituted radical selected from the group consisting of (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₁ -C ₁₂ ) alkoxy, aryloxy, (C ₁ -C ₁₂ ) lkylamino, N, N-di- (C ₁ -C ₁₂ ) alkylamino, -CH-di- (C ₁ -C ₁₂ ) alkoxy, pyrrolidinyl, pyridinyl, thiophene, imidazolyl, piperidinyl, piperazinyl, benzothiazolyl, furanyl, indolyl, morpholino, benzo [b] furanyl, quinolinyl, isoquinolinyl, - (CH ₂ ) _m- phenyl, naphthyl, fluorenyl, phthalamidyl, pyrimidinyl,

or X ¹ and X ² combine together with the nitrogen to which they are attached to form an optionally substituted radical selected from the group consisting of thiazolyl,

Y ² represents CH — X ⁴ , NX ⁴ , —C (X ⁴ X ⁴ ), O or S; X ⁴ in each case independently represents - (CH ₂ ) _m —Y ³ —X ⁵ ;
Y ³ represents —C (O) -, —C (O) O— or a bond;
X ⁵ is hydroxy, (C ₁ -C ₁₂ ) alkyl, amino, (C ₁ -C ₁₂ ) alkylamino, N, N-di- (C ₁ -C ₁₂ ) alkylamino, or an optionally substituted radical selected from the group consisting of aryl, aryl (Ci ₁ -C ₄ ) alkyl, furanyl, pyridinyl, indolyl, —CH (phenyl) ₂ ,

R ⁵ represents (C ₁ -C ₁₂ ) alkyl, (C ₀ -C ₆ ) alkyl-C (O) -OZ ⁵ , (C ₀ -C ₆ ) alkyl-C (O) -NH- (CH ₂ ) _m —Z ³ or optionally substituted aryl;
Z ³ in each case independently represents amino, (C ₁ -C ₁₂ ) alkylamino, N, N-di- (C ₁ -C ₁₂ ) alkylamino, -NH-C (O) -O- (CH ₂ ) _m - phenyl, —NH — C (O) —O— (CH ₂ ) _m - (C ₁ -C ₆ ) alkyl or an optionally substituted radical selected from the group consisting of imidazolyl, pyridinyl, morpholino, piperidinyl, piperazinyl, pyrazolidinyl, furanyl and thiophene;
R ⁶ represents H or (C ₁ -C ₆ ) alkyl;
R ⁷ represents (C ₁ -C ₁₂ ) alkyl or - (CH ₂ ) _m —Z ⁴ ;
Z ⁴ is an optionally substituted radical selected from the group consisting of phenyl, naphthyl, indolyl, thiophene, benzo [b] furan, benzo [b] thiophene, isoxazolyl,

Z ⁵ represents H, (C ₁ -C ₁₂ ) alkyl, (CH ₂ ) _m -aryl; where the optionally substituted radical is optionally substituted by one or more substituents, each of which is independently selected from the group consisting of Cl, F, Br, I, CF ₃ , CN, N ₃ , NO ₂ , OH, SO ₂ NH ₂ , -OCF ₃ , (C ₁ -C ₁₂ ) alkoxy, - (CH ₂ ) _m- phenyl- (X ⁶ ) _n , -S-phenyl- (X ⁶ ) _n , -S- (C ₁ -C ₁₂ ) alkyl, -O - (CH ₂ ) _m -phenyl- (X ⁶ ) n,
- (CH ₂ ) _m -C (O) -O- (C ₁ -C ₆ ) alkyl, - (CH ₂ ) _m -C (O) - (C ₁ -C ₆ ) alkyl, -O- (CH ₂ ) _m -NH ₂ ,
-O- (CH ₂ ) _m -NH- (C ₁ -C ₆ ) alkyl, -O- (CH ₂ ) _m -N-di - ((C ₁ -C ₆ ) alkyl) and - (C ₀ -C ₁₂ ) alkyl- (X ⁶ ) _n ;
X ⁶ in each case is independently selected from the group consisting of hydrogen, Cl, F, Br, I, NO ₂ , N ₃ , CN, OH, —CF ₃ , —OCF ₃ , (C ₁ -C ₁₂ ) alkyl, (C ₁ -C ₁₂ ) alkoxy, - (CH ₂ ) _m -NH ₂ , - (CH ₂ ) _m -NH- (C ₁ -C ₆ ) alkyl, - (CH ₂ ) _m -N-di - ((C ₁ -C ₆ ) alkyl) and - (CH ₂ ) _m- phenyl;
m in each case is independently 0 or an integer from 1 to 6 and
n in each case is independently an integer from 1 to 5; with the proviso that: (a) in the case where R ⁵ is (C ₁ -C ₁₂ ) alkyl or —C (O) —OZ ⁵ and Z ⁵ is (C ₁ -C ₁₂ ) alkyl or optionally substituted aryl; R ⁶ represents H or (C ₁ -C ₆ ) alkyl; R ⁷ is (C ₁ -C ₁₂ ) alkyl or Z ⁴ , and Z ⁴ is thiophene or optionally substituted phenyl, then R ^{3 is} not —C (O) —O— (CH ₂ ) _m Z, where m is 0, and Z represents H or (C ₁ -C ₁₂ ) alkyl, or where m is from 1 to 6, and Z represents H; (b) in the case where R ⁵ is (C ₁ -C ₁₂ ) alkyl or optionally substituted phenyl; R ⁶ represents H or (C ₁ -C ₆ ) alkyl; R ⁷ is (C ₁ -C ₁₂ ) alkyl, and R ³ is —O- (CH ₂ ) -Z ² , then Z ^{2 is} not an optionally substituted radical selected from the group consisting of phenyl, indolyl, imidazolyl, thiophene benzothiophene, pyridinyl and naphthyl; and (c) in the case where R ⁵ is H or (C ₁ -C ₁₂ ) alkyl; R ⁶ represents (C ₁ -C ₆ ) alkyl; R ⁷ represents (C ₁ -C ₁₂ ) alkyl; and R ³ is —OZ ² or —SZ ² , then Z ^{2 is} not an optionally substituted radical selected from the group consisting of phenyl, naphthyl, thiophene, benzothienyl and indolyl.

2. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ represents —CH ₂ phenyl; R ⁴ represents - (CH ₂ ) _m -A ¹ where m with respect to R ⁴ is 0; R ⁵ represents phenyl; R ⁶ represents H; where A ¹ represents-C (= Y) -N (X ¹ X ² ); Y represents O; X ¹ represents H or methyl; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; m, with reference to X ² , is 0, 1, 2 or 3;
Y ¹ represents a bond or O; and X ³ is N-methylpyrrolidin-2-yl, diethylamino, pyridinyl, thiophene, imidazolyl, diethoxymethyl, 1-benzylpiperidin-4-yl, optionally substituted phenyl or.

3. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ represents —CH ₂ phenyl; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, with respect to R ^4, is 0; R ⁵ represents phenyl; R ⁶ represents H; where A ¹ represents-C (= Y) -N (X ¹ X ² ); Y represents O; X ¹ represents benzyl and X ² represents 2-hydroxyethyl; or X ¹ and X ² combine together with the nitrogen atom to which they are attached, forming

where Y ² represents CX ⁴ or NX ⁴ ; X ⁴ represents - (CH ₂ ) _m —Y ³ —X ⁵ , where m, as applied to X ⁴ , is 0 or 1; and X ^{5 is} selected from the group consisting of furanyl, benzyl, phenyl, amino,

4. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ represents —CH ₂ phenyl; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl; R ⁶ represents H; where A ¹ represents-C (= Y) -X ² ; Y represents O; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² , is 0, 1 or 2; Y ¹ represents O, —NH — CO—, —CO — NH—, —NH — CO — 0 — CH ₂ -, SO _2, or a bond; and X ³ represents methyl, furanyl, pentyl, phenyl, indolyl, p-NO ₂ -phenyl, naphthyl, fluorenyl, -CH (phenyl) ₂ , benzothiazolyl, phthalamidyl, N, N-dimethylamino,

5. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ is —CH ₂ -indol-3-yl; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl or t-Bu; R ⁶ represents H; And ¹ represents —C (═Y) —N (X ¹ X ² ); Y represents O or S; X ¹ represents H; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; m, with reference to X ² , is 0, 1 or 2; Y ¹ represents a bond; and X ³ represents phenyl, o-Cl-phenyl, m-C1-phenyl, p-phenyloxyphenyl, 2,6-diisopropylphenyl, m-CF ₃ -phenyl, p-ethoxycarbonylphenyl, 2,4-difluorophenyl, m-NO ₃ -phenyl, p-benzyloxyphenyl, o-isopropylphenyl, n-hexyl, 4-morpholino, naphthyl

6. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ is —CH ₂ -indol-3-yl; R ⁴ represents - (CH ₂ ) _m -A ¹ where m, with respect to R ⁴ , is 0; R ⁵ represents phenyl or t-Bu; R ⁶ represents H; where A ¹ represents-C (= Y) -X ² ; Y represents O; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² , is 0, 1 or 2; Y ¹ represents O, —CO — NH—, —NH — CO — 0 — CH ₂ - or a bond; and X ³ represents methyl, 3-pentyl, phenyl, p-NO ₂ -phenyl, phthalamidyl, N, N-dimethylamino, p-aminophenyl, fluorenyl or.

7. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ is —CH ₂ -indol-3-yl; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl or t-Vi; R ⁶ represents H; where A ¹ represents-C (= Y) -N (X ¹ X ² ); Y represents O; X ¹ represents hydrogen, X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² , is 0, 1, 2 or 3; Y ¹ represents O or a bond; and X ³ represents cyclopentyl, 4-OH-butyl, N, N-diethylamino, N-methylpyrrolidin-3-yl, -CH (ethoxy) ₂ , phenyl, p-S0 ₂ NH ₂ -phenyl, p-OH-phenyl , o-CF ₃ -phenyl, p-Cl-phenyl, -CH (phenyl) ₂ ,

8. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ is —CH ₂ -indol-3-yl; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl or t-Bu; R ⁶ represents H; where A ¹ represents-C (= Y) -X ² ; Y represents O; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² , is 0, 1, 2 or 3; Y ¹ represents —NH — CO, —C = C—; -C≡C- or bond; and X ³ is tert-butyl, 1-methylcarbonylpiperidin-4-yl, phenyl, p-Cl-phenyl, m-CF ₃ -phenyl, 4-nitronaphthyl, p-methoxyphenyl, m- (phenylethyl) phenyl, indol-3 yl or p-aminophenyl.

9. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ is —CH ₂ -indol-3-yl, - (CH ₂ ) ₄ —NH — CO — O — tert-Bu, or - (CH ₂ ) ₄ —NH ₂ ; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl, o-methoxyphenyl, p-Br-phenyl, p-nitrophenyl or p-N, N-diethylaminophenyl; R ⁶ represents H; where A ¹ represents-C (= Y) -N (X ¹ X ² ); Y represents O; X ¹ represents H; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² , is 0; Y ¹ represents a bond; and X ³ represents o-Br-phenyl, m-Br-phenyl, p-Br-phenyl, o-Cl-phenyl, m-C1-phenyl, p-Cl-phenyl, o-nitrophenyl, m-nitrophenyl, p -nitrophenyl, o-CF ₃ -phenyl, m-CF ₃ -phenyl, p-CF ₃ -phenyl, p-F-phenyl, 2,4-di-F-phenyl, 2,5-di-F-phenyl, 2,5-dimethoxyphenyl, m-OMe phenyl, p-OMe phenyl, 2-CF ₃ -4-Cl-phenyl or 3-nitro-4-F-phenyl.

10. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ represents - (CH ₂ ) indol-3-yl, - (CH ₂ ) ₄ —NH — CO — O — tert-Bu, or (CH ₂ ) ₄ —NH ₃ ; R ⁴ represents - (CH ₂ ) m-A ¹ where m in relation to R ⁴ is 0; R ⁵ represents phenyl, o-methoxyphenyl, p-methoxyphenyl, p-Br-phenyl, p-nitrophenyl or p-N, N-diethylaminophenyl; R ⁶ represents H; where A ¹ represents-C (= Y) -X ² ; Y represents O; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² is 1; Y ¹ represents a bond; and X ³ represents phenyl, o-Br-phenyl, m-Br-phenyl, p-Br-phenyl, o-Cl-phenyl, m-C1-phenyl, p-C1-phenyl, o-nitrophenyl, m -nitrophenyl, p-nitro-phenyl, o-CF ₃ -phenyl, m-CF ₃ -phenyl, p-CF ₃ -phenyl, oF-phenyl, m-F-phenyl, p-F-phenyl, N, N- dimethylaminophenyl, o-OMe-phenyl, m-OMe-phenyl, p-OMe-phenyl, 3,4-di-C1-phenyl, 3,4,5-tri-OMe-phenyl, p-Me-phenyl, p- OH-phenyl or 2,4-di-F-phenyl.

11. The compound of claim 9, wherein R ⁵ is phenyl and R ³ is - (CH ₂ ) indol-3-yl, and stereochemically the carbon atom to which R ³ is attached is in R- configurations.

12. The compound of claim 10, wherein R ⁵ is phenyl and R ³ is - (CH ₂ ) indol-3-yl, and stereochemically the carbon atom to which R ³ is attached is in R- configurations.

13. The compound according to p. 10, characterized in that R ⁵ represents o-OMe-phenyl, and R ³ represents - (CH ₂ ) -indol-3-yl, and stereochemically the carbon atom to which R ³ is attached, is in R configuration.

14. The compound according to p. 10, characterized in that R ⁵ represents o-OMe-phenyl, and R ³ represents - (CH ₂ ) -indol-3-yl, and stereochemically the carbon atom to which R ³ is attached, is in S configuration.

15. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ represents - (CH ₂ ) 4-NH-CO-O-tert-Bu or - (CH ₂ ) ₄ -NH ₂ ; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl; R ⁶ represents H; where A ¹ represents-C (= Y) -X ² ; Y represents O; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² , is 0, 1 or 2;
Y ¹ represents S, SO ₂ ; or connection; and X ³ represents phenyl, 3,4-di-C1-phenyl, 3,4,5-tri-OMe-phenyl, p-Me-phenyl, p-OH-phenyl, 2,4-di-F-phenyl , 2-furanyl, 2-pyridinyl, 3-pyridinyl, naphthyl, 2-quinolinyl, 3-quinolinyl, 4-quinolinyl, 8-quinolinyl, 1-isoquinolinyl, 2-thiophene or 2-pyrimidinyl.

16. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ represents - (CH ₂ ) 4-NH-CO-O-tert-Bu or - (CH ₂ ) ₄ -NH ₂ ; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl; R ⁶ represents H; where A ¹ represents-C (= Y) -X ² ; Y represents O; X ² represents - (CH ₂ ) _m —Y ^l —X ³ , where m, as applied to X ^2, is 0, 1, 2 or 3; Y ¹ represents a bond; and X ³ is 5-indolyl, 3-indolyl, 4-indolyl, 2-indolyl, 5-OMe-indol-3-yl, 5-OMe-indol-2-yl, 5-OH-indol-2-yl 5-OH-indol-3-yl, 5-Br-in-dol-3-yl, 2-Me-indol-3-yl, 2-benzothiophene, 3-benzothiophene or 2-benzofuran.

17. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ represents - (CH ₂ ) _m -indol-3-yl, - (CH ₂ ) ₄ -NH-CO-O-tert-Bu or - (CH ₂ ) ₄ -NH ₂ ; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl, o-OMe-phenyl or p-OMe-phenyl; R ⁶ represents H; where A ¹ represents X ² ; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² represents 1, 2 or 3; Y ¹ represents S, O or a bond; and X ³ represents phenyl, o-OH-phenyl, p-OH-phenyl, oF-phenyl, m-F-phenyl, p-F-phenyl, o-CF ₃ -phenyl, o-OMe-phenyl, m- OMe-phenyl, o-nitrophenyl, p-nitrophenyl, 3,4-di-C1-phenyl, 2-nitro-3-OMe-phenyl, o-Br-phenyl, m-Br-phenyl, p-Br-phenyl, 2-thiophene, 3,4,5-tri-OMe-phenyl, p-N, N-dimethylaminophenyl, p-OCF ₃ -phenyl, p- (3- (N, N-dimethylamino) propoxy) phenyl, 3-F -4-OMe-phenyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-C1-quinolin-3-yl, 2-quinolinyl, methyl, n-butyl, n-pentyl, n-hexyl, 3.3 -dimethyl-butyl, benzyl, cyclohexyl or p-tert-Bu-phenyl.

18. The compound according to claim 1, characterized in that R ¹ represents H; R ² represents H; R ³ represents - (CH ₂ ) ₄ —NH — CO — O — tert-Bu or - (CH ₂ ) ₄ —NH2; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ^4, is O; R ⁵ represents phenyl; R ⁶ represents H; where A ¹ represents X ² ; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² , is 1, 2 or 3; Y ¹ represents O or a bond; and X ³ represents phenyl, o-OH-phenyl, p-OH-phenyl, oF-phenyl, m-F-phenyl, p-F-phenyl, o-CF ₃ -phenyl, o-OMe-phenyl, m- OMe phenyl, p-OMe phenyl, o-nitrophenyl, p-nitrophenyl, 3,4-di-Cl-phenyl, 2-nitro-3-OME phenyl, o-Br-phenyl, m-Br-phenyl, p-Br-phenyl, p-phenylphenyl, 2-thiophene, 3,4,5-tri-OMe-phenyl, p-N, N-dimethylaminophenyl, p-benzyloxyphenyl, p-OCF _3- phenyl, p- (3- (N, N-dimethylamino) propoxy) phenyl, 3-F-4-OMe-phenyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-C1-quinolin-3-yl, 2-quinolininyl, 3-indolyl 6-methoxycarbonylindol-3-yl, 1-methylindol-3-yl, 2-methylindol-3-yl, methyl, n-butyl, n-pentyl, n-hexyl, 3,3-dimethyl-buty l, benzyl, cyclohexyl or p-tert-Bu-phenyl.

19. The compound according to claim 1, characterized in that R ¹ represents - (CH ₂ ) -CO-Z ¹ ; R ² represents H; R ³ represents - (CH ₂ ) ₄ -NH-CO-O-tert-Bu, - (CH ₂ ) ₄ -NH-CO-O-benzyl, - (CH ₂ ) -phenyl or - (CH ₂ ) - indol-3-yl; R ⁴ represents - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is 0; R ⁵ represents phenyl; R ⁶ represents H; where Z ¹ represents ethyl, phenyl, p-OMe-phenyl, n-phenylphenyl, n-Cl-phenyl, p-Br-phenyl, p-N ₃ -phenyl, p-F-phenyl, m-nitrophenyl, p- nitrophenyl, p-CN-phenyl, 2,5-di-OMe-phenyl, 3,4-di-C1-phenyl, N, N-dimethylaminophenyl, 3-methyl-4-C1-phenyl or naphthyl; And ¹ represents-C (= Y) -X ² ; Y represents O; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² , is 0; Y ¹ represents O; and X ³ represents tert-Bu.

20. The compound according to claim 1, characterized in that R ¹ represents - (CH ₂ ) —CO— (CH ₂ ) _m —Z ¹ , where m, as applied to R ¹ , is 0, 1 or 2; R ² represents H; R ³ represents - (CH ₂ ) -indol-3-yl or - (CH ₂ ) ₄ -NH-CO-O-tert-Bu; R ⁴ represents H or - (CH ₂ ) _m —A ¹ where m, as applied to R ⁴ , is O; R ⁵ represents phenyl, o-OME-phenyl, p-nitrophenyl, p-Br-phenyl, tert-Bu, -CH (CH ₃ ) ₂ -CO-NH- (CH ₂ ) ₂ -CO-O-tert- Bu, -CH (CH ₃ ) ₂ -CO-NH- (CH ₂ ) _3- imidazol-1-yl, CH (CH ₃ ) ₂ -CO-NH- (CH ₂ ) ₂ -pyridin-2-yl, - CH (CH ₃ ) ₂ -CO-NH- (CH ₂ ) ₃ -4-morpholino, -CH (CH ₃ ) ₂ -CO-NH- (CH ₂ ) -pyridin-4-yl or -CH (CH ₃ ) ₂ -CO-NH- (CH ₃ ) ₂ -N, N-diethylamino; R ⁶ represents H; where Z ¹ represents ethyl, propyl, phenyl, p-OMe phenyl, p-Cl-phenyl, p-Br-phenyl, p-F-phenyl, p-nitrophenyl, m-nitrophenyl, p-CN-phenyl, p -N ₃ -phenyl, p-phenyl-phenyl, 3-Me-4-C1-phenyl, p-N, N-diethylaminophenyl, 2,5-di-OME-phenyl, 3,4-di-C1-phenyl, 3,4-di-F-phenyl, p-OCF ₃ -phenyl, p-benzyloxyphenyl, p-pentylphenyl, 3,4,5-tri-OMe-phenyl, 3-nitro-4-С1-phenyl, 3-С1 -4-nitrophenyl, 3-methyl-5-chlorobenzothiophen-2-yl, 2-benzofuranyl, 3-benzo-thiophene, 3-phenylisoxazol-5-yl, 3- (2,4-di-C1-phenyl) -isoxazole -5-yl, 3-indolyl, 5-Br-thiophen-2-yl, naphthyl,

A ¹ represents —C (═Y) —X ² ; Y represents O; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ ; where m, with reference to X ² represents 0; Y ¹ represents O; and X ³ represents tert-Bu.

21. The compound according to claim 1, characterized in that R ¹ and R ² are combined together to form a compound represented by the formula (Ib) or (1c); R ³ represents - (CH ₂ ) indol-3-yl, - (CH ₂ ) phenyl, - (CH ₂ ) _4- IN-CO-O-benzyl or - (CH ₂ ) ₂ —NH ₂ ; R ⁵ represents phenyl, o-OMe-phenyl, p-OMe-phenyl, p-Br-phenyl, p-nitrophenyl, t-Bu or —CH (CH ₃ ) ₂ —CO — NH— (CH ₂ ) ₂ - NH ₂ ; R ⁶ represents H; R ⁷ represents ethyl, propyl, phenyl, p-OMe phenyl, p-Cl-phenyl, p-Br-phenyl, p-F-phenyl, p-nitrophenyl, m-nitrophenyl, p-CN-phenyl, p- N ₃ -phenyl, p-phenylphenyl, 3-Me-4-Cl-phenyl, p-N, N-diethylaminophenyl, 2,5-di-OME-phenyl, 3,4-di-Cl-phenyl, 3,4 -di-F-phenyl, p-OCF ₃ -phenyl, p-benzyloxyphenyl, p-pentylphenyl, 3,4,5-tri-OMe-phenyl, 3-nitro-4-C1-phenyl, 3-C1-4- nitrophenyl, 3-methyl-5-chlorobenzothiophen-2-yl, 2-benzofuranyl, 3-benzothiophene, 3-phenylisoxazol-5-yl, 3- (2,4-di-Cl-phenyl) -isoxazol-5-yl, 3-indolyl, 5-Br-thiophen-2-yl, naphthyl,

22. The compound represented by formula (II),

racemic-diastereomeric mixtures and optical isomers of said compound represented by formula (II), pharmaceutically acceptable salts or prodrugs thereof or pharmaceutically acceptable salts of said prodrug, where ----- is an optional bond;
R ¹ represents H, - (CH ₂ ) _m —C (O) - (CH ₂ ) _m —Z ¹ , - (CH ₂ ) _m —Z ¹ , - (CH ₂ ) _m —O — Z ^1, or - (C ₀ -C ₆ ) alkyl-C (O) -NH- (CH ₂ ) _m -Z ³ ; Z ¹ is an optionally substituted radical selected from the group consisting of (C ₁ -C ₁₂ ) alkyl, benzo [b] thiophene, phenyl, naphthyl, benzo [b] furanyl, thiophene, isoxazolyl, indolyl,

R ² represents H or (C ₁ -C ₆ ) alkyl; or R ¹ and R ² combine together with the nitrogen atoms to which they are attached to form a compound represented by the formula (IIa), (IIb) or (11c),

R ³ represents - (CH ₂ ) _m —E— (CH ₂ ) _m —Z ² ;
E represents O, S, -C (O) -, -C (O) -O-, -NH-C (O) -O-, -N (C ₁ -C ₆ ) alkyl-C (O) - O- or bond; Z ² represents H, (C ₁ -C ₁₂ ) alkyl, amino, (C ₁ -C ₁₂ ) alkylamino, N, N-di- (C ₁ -C ₁₂ ) alkylamino, (C ₁ -C ₁₂ ) alkylguanidino, or an optionally substituted radical selected from the group consisting of phenyl, indolyl, imidazolyl, thiophene, benzothiophene, pyridinyl and naphthyl; R ⁴ represents H or - (CH ₂ ) _m —A ¹ ; And ¹ represents —C (═Y) —N (X ¹ —X ² ), —C (═Y) —X ² , —C (= NH) —X ² or X ² ; Y represents O or S; X ¹ represents H, (C ₁ -C ₁₂ ) alkyl, - (CH ₂ ) _m -NH- (C ₁ -C ₆ ) alkyl, - (CH ₂ ) _m -N-di- (C ₁ -C ₆ ) alkyl or - (CH ₂ ) _m -aryl; X ² represents - (CH ₂ ) _m —Y ¹ —X ³ or optionally substituted (C ₁ -C ₁₂ ) alkyl; Y ¹ represents O, S, NH, C = O, (C ₂ -C ₁₂ ) alkenyl containing one or more double bonds, -NH-CO-, -CO-NH-, -NH-CO-O- ( CH ₂ ) _m -, -C≡C-, SO ₂ or a bond; X ³ represents H, an optionally substituted radical selected from the group consisting of (C ₁ -C ₁₂ ) alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₁ -C ₁₂ ) alkoxy, aryloxy, (C ₁ -C ₁₂ ) alkylamino, N, N-di- (C ₁ -C ₁₂ ) alkylamino, -CH-di- (C ₁ -C ₁₂ ) alkoxy, pyrrolidinyl, pyridinyl, thiophene, imidazolyl, piperidinyl, piperazinyl, benzothiazolyl, furanyl, indolyl, morpholino, benzo [b] furanyl, quinolinyl, isoquinolinyl, - (CH ₂ ) _m- phenyl, naphthyl, fluorenyl, phthalamidyl, pyrimidinyl,

or X ¹ and X ² combine together with the nitrogen atom to which they are attached, forming an optionally substituted radical selected from the group consisting of thiazolyl,

Y ² represents CH-X ⁴ , NX ⁴ , -C (X ⁴ X ⁴ ), O or S;
X ⁴ in each case independently represents H or - (CH ₂ ) _m —Y ³ —X ⁵ ; Y ³ represents —C (O) -, —C (O) O— or a bond;
X ⁵ is hydroxy, (C ₁ -C ₁₂ ) alkyl, amino, (C ₁ -C ₁₂ ) alkylamino, N, N-di- (C ₁ -C ₁₂ ) alkylamino, or an optionally substituted radical selected from the group including aryl, aryl (C ₁ -C ₄ ) alkyl, furanyl, pyridinyl, indolyl, piperidinyl, —CH (phenyl) ₂ ,

R ⁵ represents (C ₁ -C ₁₂ ) alkyl, (C ₀ -C ₆ ) alkyl-C (O) -OZ ⁵ , (C ₀ -C ₆ ) alkyl-C (O) -NH- (CH ₂ ) _m —Z ³ or optionally substituted aryl; Z ³ in each case independently represents amino, (C ₁ -C ₁₂ ) alkylamino, amino (C ₁ -C ₁₂ ) alkyl, (C ₅ -C ₇ ) cycloalkylamino, amino (C ₅ -C ₇ ) cycloalkyl, N- (C ₁ -C ₁₂ ) alkylamino, N, N-di- (C ₁ -C ₁₂ ) alkylamino, -NH-C (O) -O- (CH ₂ ) _m- phenyl, -NH-C (O) - O- (CH ₂ ) _m - (C ₁ -C ₆ ) alkyl,

optionally substituted

or an optionally substituted radical selected from the group consisting of imidazolyl, pyridinyl, morpholino, piperidinyl, piperazinyl, pyrazolidinyl, furanyl, phenyl, indolyl and thiophene, provided that when m is 0 in the formula R ⁵ , then Z ^{3 is} not is —NH — C (O) —O— (CH ₂ ) _m —phenyl or —NH — C (O) —O— (CH ₂ ) _m - (C ₁ -C ₆ ) alkyl; R ⁶ represents H or (C ₁ -C ₆ ) alkyl; R ⁷ represents (C ₁ -C ₁₂ ) alkyl or - (CH ₂ ) _m —Z ⁴ ; Z ⁴ is an optionally substituted radical selected from the group consisting of phenyl, naphthyl, indolyl, thiophene, benzo [b] furan, benzo [b] thiophene, isoxazolyl,

Z ⁵ represents H, (C ₁ -C ₁₂ ) alkyl, or - (CH ₂ ) _m -aryl; where the optionally substituted radical is optionally substituted by one or more substituents, each independently selected from the group consisting of Cl, F, Br, I, CF ₃ , CN, N ₃ , NO ₂ , OH, SO ₂ NH ₂ , -OCF ₃ , ( C ₁ -C ₁₂ ) alkoxy, - (CH ₂ ) _m- phenyl- (X ⁶ ) _n , -S-phenyl- (X ⁶ ) n, -S- (C ₁ -C ₁₂ ) alkyl, -O- ( CH ₂ ) _{m is} phenyl- (X ⁶ ) _n ,
- (CH ₂ ) _m -C (O) -O- (C ₁ -C ₆ ) alkyl, - (CH ₂ ) _m -C (O) - (C ₁ -C ₆ ) alkyl, -O- (CH ₂ ) _m -NH ₂ ,
-O- (CH ₂ ) _m -NH- (C ₁ -C ₆ ) alkyl, -O- (CH ₂ ) _m -N-di - ((C ₁ -C ₆ ) alkyl), - (C ₀ -C ₁₂ ) alkyl- (X ⁶ ) _n and - (CH ₂ ) _m- phenyl-X ⁷ ; X ⁶ in each case is independently selected from the group consisting of hydrogen, Cl, F, Br, I, NO ₂ , N ₃ , CN, OH, —CF ₃ , —OCF ₃ , (C ₁ -C ₁₂ ) alkyl, (C ₁ -C ₁₂ ) alkoxy, - (CH ₂ ) _m -NH ₂ , - (CH ₂ ) _m -NH- (C ₁ -C ₆ ) alkyl,
- (CH ₂ ) _m -N-di - ((C ₁ -C ₆ ) alkyl) and - (CH ₂ ) _m- phenyl;
X ⁷ is —NH — C (═NH * HI) —X ⁸ where X ⁸ is thiophene, (C ₁ -C ₆ ) alkyl or phenyl; m in each case independently represents 0 or an integer from 1 to 6 and n in each case independently represents an integer from 1 to 5; ensuring that: (a) in the case where R ⁵ is (C ₁ -C ₁₂ ) alkyl or —C (O) —OZ ⁵ and Z ⁵ is (C ₁ -C ₁₂ ) alkyl or optionally substituted aryl; R ⁶ represents H or (C ₁ -C ₆ ) alkyl; R ⁷ is (C ₁ -C ₁₂ ) alkyl or Z ⁴ - and Z ⁴ is thiophene or optionally substituted phenyl, then R ^{3 is} not —C (O) —O— (CH ₂ ) _m —Z, where m represents O and Z represents H or (C ₁ -C ₁₂ ) alkyl, or where m is from 1 to 6 and Z represents H; (b) in the case where R ⁵ is (C ₁ -C ₁₂ ) alkyl or optionally substituted phenyl; R ⁶ represents H or (C ₁ -C ₆ ) alkyl; R ⁷ is (C ₁ -C ₁₂ ) alkyl and R ³ is —O- (CH ₂ ) -Z ² , then Z ^{2 is} not an optionally substituted radical selected from the group consisting of phenyl, indolyl, imidazolyl, thiophene, benzothiophene, pyridinyl and naphthyl; and (c) in case R ⁵ is H or (C ₁ -C ₁₂ ) alkyl; R ⁶ represents (C ₁ -C ₆ ) alkyl; R ⁷ represents (C ₁ -C ₁₂ ) alkyl; and R ³ is —OZ ² or —SZ ² , then Z ^{2 is} not an optionally substituted radical selected from the group consisting of phenyl, naphthyl, thiophene, benzothienyl and indolyl.

23. The compound according to p. 22, characterized in that

where Z ³ represents —CH ₂ —NH ₂ , - (CH ₂ ) ₂ —NH ₂ , - (CH ₂ ) ₃ —NH _2, or

and X ¹ represents - (CH ₂ ) ₂ —N (CH ₃ ) ₂ and X ² represents benzyl; or X ¹ and X ² combine together with the nitrogen atom to which they are attached, forming

24. The compound according to p. 22, characterized in that it has the following formula

where Z ³ represents

25. The compound according to p. 22, characterized in that it has the following formula

where X ² represents p-chlorophenyl, p-methoxyphenyl, 2,4-difluorophenyl or thienyl.

26. The compound according to p. 22, characterized in that it has the following formula

where X ² represents p-chlorophenyl, p-methoxyphenyl, phenyl or thienyl.

27. The compound according to p. 22, characterized in that it has the following formula

28. The compound according to p. 22, characterized in that it has the following formula

29. The compound according to p. 22, characterized in that it has the following formula

where R ⁵ represents

and R ⁷ is m-nitrophenyl or 2-phenylethyl; or
R ⁵ represents

and R ⁷ represents

; or
R ⁵ represents

and R ⁷ represents 3,4-dichlorophenyl or

or R ⁵ represents

and R ⁷ is 3,4-dichlorophenyl.

30. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

31. A method of binding one or more subtypes of a somatostatin receptor to a subject in need thereof, which comprises administering a compound of claim 1 or a pharmaceutically acceptable salt thereof to said subject.

32. The method according to p. 31 to enhance the agonistic effect on one or more subtypes of somatostatin receptor.

33. The method according to p. 31 to enhance the antagonistic effect on one or more subtypes of somatostatin receptor.

34. The method according to p. 31 in the treatment of acromegaly, restenosis, Crohn’s disease, systemic sclerosis, external and internal pseudocysts and pancreatic ascites, apudoma, insuloma, hyperinsulinism, gastrinoma, Zollinger-Ellison syndrome, diarrhea, AIDS-associated diarrhea, diarrhea, chemotherapy, scleroderma, irritable bowel syndrome, pancreatitis, small bowel obstruction, gastroesophageal reflux, duodenogastric reflux, Cushing's syndrome, gonadotropinoma, hyperparathyroidism, Graves disease, diabetic neuropathy, Paget's disease, polycystic ovaries, malignant tumors, cancer cachexia, hypotension, hypotension, postprandial, panic attacks, GH-secreting adenomas or TSH-secreting adenomas, in a subject in need thereof.

35. The method according to p. 31 in the treatment of diabetes mellitus, hyperlipidemia, insulin resistance, X syndrome, angiopathy, proliferative retinopathy, dawn phenomenon, nephropathy, peptic ulcers, intestinal and pancreatic fistulas, dumping syndrome, watery stool syndrome, acute or chronic pancreatitis, tumors secreting hormones of the gastrointestinal tract, angiogenesis, inflammatory diseases, chronic allograft rejection, angioplasty, bleeding from the vessels of the graft and gastrointestinal tract the giver, in this subject.

36. A method of inhibiting the proliferation of Helicobacter pylori in a subject in need thereof, comprising administering a compound of claim 1 or a pharmaceutically acceptable salt thereof to said subject.

37. A pharmaceutical composition comprising the compound of Claim 22 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

38. A method of binding one or more subtypes of a somatostatin receptor to a subject in need thereof, characterized in administering the compound of claim 22 or a pharmaceutically acceptable salt thereof to said subject.

39. The method of claim 38 for enhancing an agonistic effect on one or more subtypes of a somatostatin receptor in a subject.

40. The method according to p. 38 to enhance the antagonistic effect on one or more subtypes of a somatostatin receptor in a subject.

41. The method according to p. 38 in the treatment of acromegaly, restenosis, Crohn’s disease, systemic sclerosis, external and internal pseudocysts and pancreatic ascites, apudoma, insuloma, hyperinsulinism, gastrinoma, Zollinger-Ellison syndrome, diarrhea, AIDS-associated diarrhea, diarrhea, chemotherapy, scleroderma, irritable bowel syndrome, pancreatitis, small bowel obstruction, gastroesophageal reflux, duodenogastric reflux, Cushing's syndrome, gonadotropinoma, hyperparathyroidism, Graves disease, diabetic neuropathy, Paget's disease, polycystic ovaries, malignant tumors, cancer cachexia, hypotension, hypotension, postprandial, panic attacks, GH-secreting adenomas or TSH-secreting adenoma in a subject in need thereof.

42. The method according to p. 38 in the treatment of diabetes mellitus, hyperlipidemia, insulin resistance, X syndrome, angiopathy, proliferative retinopathy, dawn phenomenon, nephropathy, peptic ulcers, intestinal and pancreatic fistulas, dumping syndrome, watery stool syndrome, acute or chronic pancreatitis, tumors secreting hormones of the gastrointestinal tract, angiogenesis, inflammatory diseases, chronic allograft rejection, angioplasty, bleeding from the vessels of the graft and gastrointestinal tract the giver, in this subject.

43. A method of inhibiting the proliferation of Helicobacter pylori in a subject in need thereof, characterized in administering the compound of claim 22 or a pharmaceutically acceptable salt thereof to said subject.