RU2003100534A

RU2003100534A - DERIVATIVES OF AMINO ALCOHOLS, PHARMACEUTICAL COMPOSITION, METHOD FOR PREVENTION OR TREATMENT, INTERMEDIATE COMPOUNDS AND METHOD FOR PRODUCING INTERMEDIATE COMPOUNDS

Info

Publication number: RU2003100534A
Application number: RU2003100534/04A
Authority: RU
Inventors: Такахиде НИСИ; Тосиясу ТАКЕМОТО; Такаити СИМОЗАТО; Футоси НАРА
Original assignee: Санкио Компани, Лимитед
Priority date: 2000-07-13
Filing date: 2001-07-10
Publication date: 2004-05-27

Claims

1. The compound of formula (I) or its pharmacologically acceptable salt, ester or other derivative

where R ¹ and R ² are the same or different and represent each hydrogen atom or amino protecting group;

R ³ represents a hydrogen atom or a hydroxy protecting group;

R ⁴ represents a lower alkyl group;

n is 1-6;

X represents an ethylene group, a vinylene group, an ethylene group, a group of the formula —D — CH ₂ - (where D represents a carbonyl group, a group of the formula —CH (OH) -, an oxygen atom, a sulfur atom or a nitrogen atom), an aryl group or an aryl group substituted by 1-3 substituents selected from group a of substituents;

Y represents a single bond, a C ₁ -C ₁₀ alkylene group, a C ₁ -C ₁₀ alkylene group substituted by 1-3 substituents selected from substituent groups a and b, a C ₁ -C ₁₀ alkylene group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or a C ₁ -C ₁₀ alkylene group substituted by 1-3 substituents selected from groups a and b of the substituents, and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain ;

R ⁵ represents a hydrogen atom, a cycloalkyl group, an aryl group, a heterocyclic group, a cycloalkyl group substituted by 1-3 substituents selected from substituent groups a and b, an aryl group substituted by 1-3 substituents selected from substituent groups a and b, or a heterocyclic group substituted by 1-3 substituents selected from groups a and b of substituents;

R ⁶ and R ⁷ are the same or different and represent each hydrogen atom or a group selected from group a of substituents,

with the proviso that when R ⁵ represents a hydrogen atom, then Y is not a single bond or an unbranched C ₁ -C ₁₀ alkylene group;

the substituent group a consists of a halogen atom, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group, a lower alkylthio group, a carboxyl group, a lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, an amino group, a lower monoalkylamino group, a lower dialkylamino amino group, a lower dialkylamino group cyano groups and nitro groups;

substituent group b consists of a cycloalkyl group, an aryl group, a heterocyclic group, a cycloalkyl group substituted by 1-3 substituents selected from a substituent group a, an aryl group substituted by 1-3 substituents selected from substituent group a, and a heterocyclic group substituted by 1 -3 substituents selected from group a of the substituents.

2. The compound according to claim 1, where the specified compound has the formula (Ia), or its pharmacologically acceptable salt, ester or other derivative

3. The compound according to claim 1, where the specified compound has the formula (Ib), or its pharmacologically acceptable salt, ester or other derivative

4. The compound according to any one of claims 1 to 3, where R ¹ and R ² are the same or different and represent each hydrogen atom, a lower alkoxycarbonyl group, an aralkyloxycarbonyl group or an aralkyloxycarbonyl group substituted with 1-3 substituents selected from group a of the substituents, or a pharmacologically acceptable salt, ester or other derivative thereof.

5. The compound according to any one of claims 1 to 3, where each of R ¹ and R ² represents a hydrogen atom, or its pharmacologically acceptable salt, ester or other derivative.

6. The compound according to any one of claims 1 to 5, where R ³ represents a hydrogen atom, a lower alkyl group, a lower aliphatic acyl group, an aromatic acyl group or an aromatic acyl group substituted by 1-3 substituents selected from the group of substituents, or a pharmacologically acceptable salt, ester or other derivative.

7. The compound according to any one of claims 1 to 5, where R ³ represents a hydrogen atom, or its pharmacologically acceptable salt, ester or other derivative.

8. The compound according to any one of claims 1 to 7, where R ⁴ represents a C ₁ -C ₄ alkyl group, or a pharmacologically acceptable salt, ester or other derivative thereof.

9. The compound according to any one of claims 1 to 7, where R ⁴ represents a C ₁ -C ₂ alkyl group, or a pharmacologically acceptable salt, ester or other derivative thereof.

10. The compound according to any one of claims 1 to 7, where R ⁴ represents a methyl group, or its pharmacologically acceptable salt, ester or other derivative.

11. The compound according to any one of claims 1 to 10, where n = 2 or 3, or its pharmacologically acceptable salt, ester or other derivative.

12. The compound according to any one of claims 1 to 10, where n = 2, or its pharmacologically acceptable salt, ester or other derivative.

13. The compound according to any one of claims 1 to 12, where X represents an ethylene group, an ethylene group, an aryl group or an aryl group substituted by 1-3 substituents selected from substituent group a, or a pharmacologically acceptable salt, ester or other derivative thereof .

14. The compound according to any one of claims 1 to 12, where X represents an ethylene group, or a pharmacologically acceptable salt, ester or other derivative thereof.

15. The compound according to any one of claims 1 to 12, where X represents an ethylene group, or a pharmacologically acceptable salt, ester or other derivative thereof.

16. The compound according to any one of claims 1 to 12, where X represents a group of the formula-D-CH ₂ -, or a pharmacologically acceptable salt, ester or other derivative thereof.

17. The compound according to any one of claims 1 to 12, where X represents a group of the formula —D — CH ₂ - (where D represents a carbonyl group or a group of the formula —CH (OH) -), or a pharmacologically acceptable salt, ester or other thereof derivative.

18. The compound according to any one of claims _{1 to} ₁₇ , where Y represents a C ₁ -C ₁₀ alkylene group or a C ₁ -C ₁₀ alkylene group substituted by 1-3 substituents selected from substituent groups a and b, or a pharmacologically acceptable salt thereof ester or other derivative.

19. The compound according to any one of claims 1 to 17, where Y represents a C ₁ -C ₆ alkylene group or a C ₁ -C ₆ alkylene group substituted by 1-3 substituents selected from substituent groups a and b, or a pharmacologically acceptable salt thereof ester or other derivative.

20. The compound according to any one of claims 1 to 17, where Y represents an ethylene group, a trimethylene group, a tetramethylene group, an ethylene group substituted by 1-3 substituents selected from substituent groups a and b, a trimethylene group substituted by 1-3 substituents, selected from groups a and b of substituents, or a tetramethylene group substituted with 1-3 substituents selected from groups a and b of substituents, or a pharmacologically acceptable salt, ester or other derivative thereof.

21. The compound according to any one of claims 1 to 17, where Y represents an ethylene group, a trimethylene group or a tetramethylene group, or a pharmacologically acceptable salt, ester or other derivative thereof.

22. The compound according to any one of claims 1 to 17, where Y represents an ethylene group or a trimethylene group, or a pharmacologically acceptable salt, ester or other derivative thereof.

23. The compound according to any one of claims _{1 to} ₁₇ , where Y represents a C ₁ -C ₁₀ alkylene group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or a C ₁ -C ₁₀ alkylene group substituted 1-3 substituents selected from groups a and b of the substituents, and containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or its pharmacologically acceptable salt, ester or other derivative.

24. The compound according to any one of claims _{1 to} ₁₇ , where Y represents a C ₁ -C ₁₀ alkylene group containing an oxygen atom or a sulfur atom in the specified carbon chain or at the end of the specified carbon chain, or its pharmacologically acceptable salt, ester or other derivative.

25. The compound according to any one of claims _{1 to} ₁₇ , where Y represents a C ₁ -C ₁₀ alkylene group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or its pharmacologically acceptable salt, ester or other derivative.

26. The compound according to any one of claims 1 to 17, where Y represents a C ₁ -C ₆ alkylene group containing an oxygen atom in the specified carbon chain or at the end of the specified carbon chain, or its pharmacologically acceptable salt, ester or other derivative.

27. The compound according to any one of claims 1 to 17, where Y represents a group of the formula —O — CH ₂ -, —O— (CH ₂ ) ₂ -, —O— (CH ₂ ) _3-, —CH ₂ —O— , - (CH ₂ ) ₂ -O- or - (CH ₂ ) ₃ -O-, or a pharmacologically acceptable salt, ester or other derivative thereof.

28. The compound according to any one of claims 1 to 17, where Y represents a group of the formula —CH ₂ —O—, or a pharmacologically acceptable salt, ester or other derivative thereof.

29. The compound according to any one of claims 1 to 17, where Y represents a group of the formula -O- (CH ₂ ) ₂ - or (CH ₂ ) ₂ -O-, or a pharmacologically acceptable salt, ester or other derivative thereof.

30. The compound according to any one of claims 1 to 29, where R ⁵ represents a hydrogen atom, or its pharmacologically acceptable salt, ester or other derivative.

31. The compound according to any one of claims 1 to 29, where R ⁵ represents a cycloalkyl group, a heterocyclic group, a cycloalkyl group substituted by 1-3 substituents selected from substituent groups a and b, or a heterocyclic group substituted by 1-3 substituents selected from groups a and b of substituents, or a pharmacologically acceptable salt, ester or other derivative thereof.

32. The compound according to any one of claims 1 to 29, where R ⁵ represents a cycloalkyl group or a cycloalkyl group substituted by 1-3 substituents selected from substituent groups a and b, or a pharmacologically acceptable salt, ester or other derivative thereof.

33. The compound according to any one of claims 1 to 29, where R ⁵ represents a cycloalkyl group, or a pharmacologically acceptable salt, ester or other derivative thereof.

34. The compound according to any one of claims 1 to 29, where R ⁵ represents a cyclohexyl group, or a pharmacologically acceptable salt, ester or other derivative thereof.

35. The compound according to any one of claims 1 to 29, where R ⁵ represents an aryl group or an aryl group substituted by 1-3 substituents selected from substituent groups a and b, or a pharmacologically acceptable salt, ester or other derivative thereof.

36. The compound according to any one of claims 1 to 29, where R ⁵ represents an aryl group or an aryl group substituted by 1-3 substituents (said substituent is selected from the group consisting of a halogen atom, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group , lower alkylthio group and lower aliphatic acyl group), or a pharmacologically acceptable salt, ester or other derivative thereof.

37. The compound according to any one of claims 1 to 29, where R ⁵ represents an aryl group or an aryl group substituted by 1-3 substituents (said substituent is selected from the group consisting of a halogen atom, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group), or a pharmacologically acceptable salt, ester or other derivative thereof.

38. The compound according to any one of claims 1 to 29, where R ⁵ represents a phenyl group or a phenyl group substituted by 1-3 substituents (said substituent is selected from the group consisting of a halogen atom, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group and a lower aliphatic acyl group), or a pharmacologically acceptable salt, ester or other derivative thereof.

39. The compound according to any one of claims 1 to 29, where R ⁵ represents a phenyl group or a phenyl group substituted by 1-3 substituents (said substituent is selected from the group consisting of fluorine atom, chlorine atom, methyl, trifluoromethyl, methoxy and acetyl groups ), or a pharmacologically acceptable salt, ester or other derivative thereof.

40. The compound according to any one of claims 1 to 29, where R ⁵ represents phenyl, 3-fluorophenyl, 4-fluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3,4- dichlorophenyl, 3,5-dichlorophenyl, 3-methylphenyl, 4-methylphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 3,4-ditrifluoromethylphenyl, 3,5-ditrifluoromethylphenyl, 3- methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3,5-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3-acetylphenyl or 4-acetylphenyl, or a pharmacologically acceptable salt, ester or other derivative thereof.

41. The compound according to any one of claims 1 to 40, where R ⁶ and R ⁷ are the same or different and represent each hydrogen atom, a halogen atom, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group or a lower alkylthio group, or a pharmacologically acceptable thereof salt, ester or other derivative.

42. The compound according to any one of claims 1 to 40, where each of R ⁶ and R ⁷ represents a hydrogen atom, or its pharmacologically acceptable salt, ester or other derivative.

43. The compound according to claim 1, where the specified compound or its pharmacologically acceptable salts, esters or other derivatives are selected from the following compounds, including:

2-amino-2-methyl-4- [5- (6-cyclohexylhexyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexylpentyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexylbutyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (6-cyclohexylhex-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (6-cyclohexylhexanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexylbutanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (6-cyclohexylhexyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (5-cyclohexylpentyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (4-cyclohexylbutyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (6-cyclohexylhex-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (4-cyclohexylbut-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (6-cyclohexylhexanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (4-cyclohexylbutanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (6-phenylhexyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenylpentyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenylbutyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (6-phenylhex-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenylbut-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (6-phenylhexanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenylpentanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenylbutanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexyloxypent-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexyloxybut-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (3-cyclohexyloxypropinyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexyloxypentyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexyloxybutyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (3-cyclohexyloxypropyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexyloxypentanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexyloxybutanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (3-cyclohexyloxypropanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenoxypent-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenoxybut-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (3-phenoxypropinyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenoxypentyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenoxybutyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (3-phenoxypropyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenoxypentanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenoxybutanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (3-phenoxypropanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-benzyloxyphenyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexylmethoxyphenyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexylethoxyphenyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (3-cyclohexylmethoxypropinyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (3-cyclohexylmethoxypropyl) thiophen-2-yl] butan-1-ol and

2-amino-2-methyl-4- [5- (3-cyclohexylmethoxypropanoyl) thiophen-2-yl] butan-1-ol.

44. The compound according to claim 1, where the specified compound or its pharmacologically acceptable salts, esters or other derivatives are selected from the following compounds, including:

2-amino-2-methyl-4- [5- (4-cyclohexylbutyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexylpentyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenylpentyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexyloxybutyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- {5- [4- (4-fluorophenoxy) butyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [4- (4-methoxyphenoxy) butyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- [5- (4-benzyloxybutyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexylbut-1-ynyl) thiophen-2-ol] butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenylbut-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenylpent-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- {5- [5- (4-fluorophenyl) pent-1-ynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [5- (4-methoxyphenyl) pent-1-ynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (4-methylcyclohexyloxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (4-methylphenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (4-ethylphenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (4-methylthiophenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexyloxybut-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- {5- [4- (4-fluorophenoxy) but-1-ynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [4- (4-methylphenoxy) but-1-ynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenylmethoxybut-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-cyclohexylbutanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (4-phenylbutanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- [5- (5-phenylpentanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- {5- [5- (4-fluorophenyl) pentanoyl] thiophen-2-yl} butan-1-ol,

2-amino-2-ethyl-4- [5- (5-cyclohexylpentyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (5-cyclohexylpent-1-ynyl) thiophen-2-yl] butan-1-ol,

2-amino-2-ethyl-4- [5- (5-cyclohexylpentanoyl) thiophen-2-yl] butan-1-ol,

2-amino-2-methyl-4- {5- [3- (4-chlorophenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (3-methylphenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (3,4-dimethylphenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (3-methoxyphenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (3,4-dimethoxyphenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (3,5-dimethoxyphenoxy) propynyl] thiophen-2-yl} butan-1-ol,

2-amino-2-methyl-4- {5- [3- (3-acetylphenoxy) propynyl] thiophen-2-yl} butan-1-ol and

2-amino-2-methyl-4- {5- [3- (4-acetylphenoxy) propynyl] thiophen-2-yl} butan-1-ol.

45. A pharmaceutical composition comprising a pharmaceutically acceptable diluent or carrier and a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to any one of claims 1 to 44.

46. The pharmaceutical composition according to item 45 for the prevention or treatment of autoimmune disease.

47. The pharmaceutical composition according to item 45, where the specified autoimmune disease is rheumatoid arthritis.

48. The pharmaceutical composition according to item 45 for the suppression of immunological rejection after organ transplantation.

49. The compound of formula (I) or its pharmacologically acceptable salt, ester or other derivative according to any one of claims 1 to 44 for use as a means for the prevention or treatment of autoimmune disease.

50. The compound of claim 49, wherein said autoimmune disease is rheumatoid arthritis.

51. The compound of claim 49, wherein said agent is a means for suppressing immunological rejection after organ transplantation.

52. A method for the prevention or treatment of an autoimmune disease in a warm-blooded animal, which may be a human, comprising administering a pharmacologically effective amount of a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to any one of claims 1 to 44, in need of this warm-blooded to the animal.

53. The method of claim 52, wherein said autoimmune disease is rheumatoid arthritis.

54. The method according to paragraph 52, to suppress immunological rejection after organ transplantation.

55. The compound of formula (La) or (Lb):

or

where R ¹ and R ² are the same or different and represents each hydrogen atom or an amino protecting group;

R ^3a represents a hydrogen atom or a hydroxy protecting group or, when R ¹ represents a hydrogen atom, R ² and R ^3a , taken together, form a group of the formula - (C = O) -;

R ^4a represents a C ₁ -C ₂₀ alkyl group, a C ₂ -C ₂₀ alkyl group interrupted by a heteroatom (s), a C ₁ -C ₂₀ alkyl group substituted by an aryl group (s) or a heteroaryl group (s), C ₂ -C ₂₀ alkynyl group, C ₃ -C ₂₀ alkynyl group interrupted by heteroatom (s), C ₂ -C ₂₀ alkynyl group substituted by aryl group (s) or heteroaryl group (s), C ₂ -C ₂₀ alkenyl group, C ₃ - C ₂₀ alkenyl group interrupted by heteroatom (s), C ₂ -C ₂₀ alkenyl group substituted by aryl group (s) or heteroaryl group (s), C ₂ -C ₂₀ a an alkyl group substituted with an aryl group (s) or a heteroaryl group (s) and interrupted by a heteroatom (s), or a cycloalkyl group;

m is 0 to 4;

Ar represents an aryl group, a heteroaryl group, an aryl group substituted by 1-5 substituents selected from substituent group a, a heteroaryl group substituted by 1-5 substituents selected from substituent group a,

with the proviso that when Ar represents an aryl group, R ^{1 is} not a hydrogen atom and R ² and / or R ^3a does not represent a hydrogen atom;

the substituent group a includes a halogen atom, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group, a lower alkylthio group, a carboxyl group, a lower alkoxycarbonyl group, a hydroxyl group, a lower aliphatic acyl group, an amino group, a lower monoalkylamino group, a lower aminoalkylamino group, a lower diaminoalkylamino group and nitro group.

56. The compound of claim 55, wherein said compound has the formula (La).

57. The compound of claim 55 or 56, wherein R ¹ is a hydrogen atom.

58. The compound according to any one of paragraphs.55-57, where R ² and R ^3a , taken together, form a group of the formula - (C = O) -.

59. The compound according to any one of paragraphs.55-57, where R ^3a represents a hydrogen atom.

60. The compound according to any one of paragraphs.55-59, where R ^4a represents a C ₁ -C ₁₀ alkyl group, a C ₂ -C ₁₀ alkyl group interrupted by heteroatom (s), a C ₁ -C ₁₀ alkyl group substituted by an aryl group ( s) or a heteroaryl group (s), a C ₂ -C ₁₀ alkynyl group, a C ₃ -C ₁₀ alkynyl group interrupted by a heteroatom (s), a C ₂ -C ₁₀ alkynyl group substituted by an aryl group (s) or a heteroaryl group (s) ), A C ₂ -C ₁₀ alkenyl group, a C ₃ -C ₁₀ alkenyl group interrupted by a heteroatom (s), a C ₂ -C ₁₀ alkenyl group substituted by an aryl group (s) or heteroaryl group (s), C ₂ -C ₁₀ alkyl group substituted by aryl group (s) or heteroaryl group (s) and interrupted by heteroatom (s), or C ₅ -C ₁₀ cycloalkyl group.

61. The compound according to any one of paragraphs.55-59, where R ^4a represents a C ₁ -C ₁₀ alkyl group, a C ₂ -C ₁₀ alkyl group interrupted by heteroatom (s), a C ₁ -C ₁₀ alkyl group substituted by an aryl group ( s) or a heteroaryl group (s), a C ₂ -C ₁₀ alkynyl group, a C ₂ -C ₁₀ alkenyl group or a C ₅ -C ₁₀ cycloalkyl group.

62. The compound according to any one of paragraphs.55-59, where R ^4a represents a C ₁ -C ₁₀ alkyl group.

63. The compound according to any one of paragraphs.55-59, where R ^4a represents a C ₁ -C ₆ alkyl group.

64. The compound according to any one of paragraphs.55-59, where R ^4a represents a methyl group or ethyl group.

65. The compound according to any one of claims 55-64, wherein Ar represents a phenyl, furyl, thienyl or benzothienyl group, said groups being optionally substituted with 1-4 substituents selected from substituent group a.

66. The compound according to any one of claims 55-64, wherein Ar is a thienyl group or a thienyl group substituted with 1-4 substituents selected from substituent group a.

67. The compound according to any one of paragraphs.55-64, where Ar represents a benzothienyl group or a benzothienyl group substituted with 1-4 substituents selected from substituent group a.

68. The compound of claims 55-67, where m = 0.

69. The compound according to any one of claims 55-68, wherein the substituent group a is a halogen atom, a hydroxyl group, a lower alkyl group, a halogenated lower alkyl group, a lower alkoxy group, a carboxyl group, a lower aliphatic acyl group, a lower aliphatic acylamino group, an amino group, cyano group or nitro group.

70. A method of obtaining a compound of formula (XLIVa) or XLIVb)

or

R ^4a represents a C ₁ -C ₂₀ alkyl group, a C ₂ -C ₂₀ alkyl group interrupted by a heteroatom (s), a C ₁ -C ₂₀ alkyl group substituted by an aryl group (s) or a heteroaryl group (s), C ₂ -C ₂₀ alkynyl group, C ₃ -C ₂₀ alkynyl group interrupted by heteroatom (s), C ₂ -C ₂₀ alkynyl group substituted by aryl group (s) or heteroaryl group (s), C ₂ -C ₂₀ alkenyl group, C ₃ - C ₂₀ alkenyl group interrupted by heteroatom (s), C ₂ -C ₂₀ alkenyl group substituted by aryl group (s) or heteroaryl group (s), C ₂ -C ₂₀ an alkyl group substituted with an aryl group (s) or a heteroaryl group (s) and interrupted by a heteroatom (s), or a cycloalkyl group;

R ¹¹ has the same meaning as described above for R ^4a , which includes the selective acylation of one hydroxyl group of a 2-substituted 2-amino-1,3-propanediol derivative of the formula (XLII)

where R ¹ , R ² and R ^4a are as defined above,

a carboxylic acid ester derivative of the formula (XLIII)

R ¹¹ COOCH = CH ₂ , (XLIII),

where R ¹¹ is the same as defined above,

in the presence of lipase to obtain a 2-substituted derivative of a 2-amino-1,3-propanediol monoester of formula (XLIVa) or (XLIVb).

71. The production method according to item 70, where one of R ¹ and R ² represents a hydrogen atom, and the other is an amino-protecting group.

72. The production method according to item 70 or 71, wherein R ^4a represents a C ₁ -C ₁₀ alkyl group, a C ₂ -C ₁₀ alkyl group interrupted by a heteroatom (s), a C ₁ -C ₁₀ alkyl group substituted by an aryl group (s) ) or a heteroaryl group (s), a C ₂ -C ₁₀ alkynyl group, a C ₃ -C ₁₀ alkynyl group interrupted by a heteroatom (s), a C ₂ -C ₁₀ alkynyl group substituted by an aryl group (s) or a heteroaryl group (s) C ₂ -C ₁₀ alkenyl group, C ₃ -C ₁₀ alkenyl group interrupted with a heteroatom (s), a C ₂ -C ₁₀ alkenyl group substituted with aryl group (s) or g teroarilnoy group (s), C ₂ -C ₁₀ alkyl group substituted with aryl group (s) or a heteroaryl group (s) and interrupted with a heteroatom (s) or C ₅ -C ₁₀ cycloalkyl group.

73. The production method according to item 70 or 71, where R ^4a represents a C ₁ -C ₁₀ alkyl group, a C ₂ -C ₁₀ alkyl group interrupted by a heteroatom (s), a C ₁ -C ₁₀ alkyl group substituted by an aryl group (s) ) or a heteroaryl group (s), a C ₂ -C ₁₀ alkynyl group, a C ₂ -C ₁₀ alkenyl group, or a C ₅ -C ₁₀ cycloalkyl group.

74. The production method according to claims 70-73, wherein R ¹¹ is a C ₁ -C ₂₀ alkyl group or a C ₁ -C ₂₀ alkyl group substituted with an aryl group (s) or heteroaryl group (s).