Heteroaryl-substituted pyrrole derivatives, their preparation and their therapeutic uses

• US 20040054173A1
• Filed: 01/30/2003
• Published: 03/18/2004
• Est. Priority Date: 07/21/1999
• Status: Active Grant

• Current Assignee: Sankyo Company Limited (Daiichi Sankyo Company Limited)
• Original Assignee: Sankyo Company Limited (Daiichi Sankyo Company Limited)
• Inventors: Shimozato, Takaichi, Nakao, Akira, Aoki, Kazumasa, Kimura, Tomio, Yamazaki, Takanori, Nagasaki, Takayoshi, Ohkawa, Nobuyuki, Ushiyama, Shigeru
• Granted Patent: US 7,122,666 B2
• Time in Patent Office: Days
• US Class Current: 544/60
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 451/02 containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
• CPC Class Codes: C07D 453/02 containing not further condensed quinuclidine ring systems
• CPC Class Codes: C07D 455/02 containing not further condensed quinolizine ring systems
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Compounds having activity against production of an inflammatory cytokine of formula (I)′:

A′ is pyrrole; R^1′ is phenyl or naphthyl; R^2′ is pyridyl or pyrimidinyl; R^3′ is (IIa)′, (IIb)′ or (IIc)′:

m′ is 1; E′ is nitrogen; D′ is >C(R^5′)—, R^5′ is hydrogen, Substituent α′ or Substituent β′; B′ is nitrogen-containing 5-membered heterocyclic; R^4′ is 1 to 3 substituents from Substituent α′, Substituent β′ and Substituent γ′; R^1′ and R^3′ are bonded to two atoms of the pyrrole adjacent to the pyrrole atom bonded to R^2′; Substituent α′ is hydroxyl, nitro, cyano, halogen, alkoxy, halogeno alkoxy, alkylthio, halogeno alkylthio or —NR^a′R^b′; R^a′ and R^b′ are hydrogen, alkyl, alkenyl, alkynyl, aralkyl or alkylsulfonyl, or R^a′ and R^b′ with the nitrogen atom form a heterocyclyl; Substituent β′ is alkyl, alkenyl, alkynyl, aralkyl or cycloalkyl; Substituent γ′ is oxo, hydroxyimino, alkoxyimino, alkylene, alkylenedioxy, alkylsulfinyl, alkylsulfonyl, aryl, aryloxy, alkylidenyl or aralkylidenyl.

Claims

1. (Three Times Amended) A compound of formula (I), or a pharmacologically acceptable salt, ester or other derivative thereof:

2. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R¹ is a phenyl group which is optionally substituted with at least one substituent selected from the group consisting of Substituent group α

¹ defined below, Substituent group β

¹ defined below, Substituent group γ

¹ defined below and Substituent group δ

¹ defined below;

said Substituent group α

¹ is selected from the group consisting of halogen atoms, lower alkoxy groups as defined in claim 1 and halogeno lower alkoxy groups as defined in claim 1;

said Substituent group β

¹ is selected from the group consisting of a group of formula —

NR^cR^d wherein one of R^c and R^d is selected from the group consisting of hydrogen atoms and lower alkyl groups as defined in claim 1 and the other is selected from the group consisting of hydrogen atoms, lower alkyl groups as defined in claim 1 and aralkyl groups as defined in claim 1;

said Substituent group γ

¹ is selected from the group consisting of lower alkyl groups as defined in claim 1 which are substituted with a substituent selected from the group consisting of amino groups, amino groups substituted with one or two lower alkyl groups as defined in claim 1 and amino groups substituted with an aralkyl group as defined in claim 1;

and

said Substituent group δ

¹ is selected from the group consisting of lower alkyl groups as defined in claim 1, halogeno lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one halogen atom, hydroxy lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one hydroxy group and nitro lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one nitro group.

3. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R¹ is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one halogen atom and halogeno lower alkoxy groups as defined in claim 1.

4. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R¹ is selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups.

5. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R² is a 4-pyridyl or 4-pyrimidinyl group which optionally is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

.

6. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R² is a 4-pyridyl or 4-pyrimidinyl group which optionally is substituted at the 2-position thereof with a substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

.

7. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R² is a 4-pyridyl or 4-pyrimidinyl group which optionally is substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino and α

-methylbenzylamino groups.

8. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein in R³, m is 1 and n is 1.

9. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein in R³, E represents a group of formula >

NR¹⁰ and D represents a group of formula >

CR¹¹R¹².

10. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein in R³, one of R⁵ and R⁷ together with R⁶ represents a single bond and the other represents a substituent selected from the group consisting of hydrogen atoms, Substituent group α

, Substituent group γ and

Substituent group δ

;

R⁸, R⁹ and R¹² are the same or different from one another and each represents a substituent selected from the group consisting of hydrogen atoms, Substituent group α

, Substituent group γ and

Substituent group δ

; and

R¹⁰ and R¹¹ are the same or different from one another and each represents a substituent selected from the group consisting of hydrogen atoms, Substituent group α

, Substituent group γ and

Substituent group δ

;

or R¹⁰ and R¹¹ together form an alkylene group having from 1 to 6 carbon atoms which is unsubstituted or is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

.

11. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein in R³, R¹⁰ and R¹¹ together form a straight chain alkylene group having 3 or 4 carbon atoms which is unsubstituted or is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

.

12. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein in R³, each of R⁷, R⁸ and R⁹ is a hydrogen atom, and R¹⁰ and R¹¹ together form a straight chain alkylene group having 3 or 4 carbon atoms which is unsubstituted or is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

.

13. A compound according to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein said compound of formula (I) is a compound of formula (I-1) or (I-3) below:

14. A compound according to claim 1 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R¹ is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of Substituent group α

¹ defined below, Substituent group β

¹ defined below, Substituent group γ

¹ defined below and Substituent group δ

¹ defined below;

R² is a 4-pyridyl or 4-pyrimidinyl group which optionally is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

; and

R³ is a group of formula (II) as defined in claim 1 wherein m is 1 and n is 1;

said Substituent group α

¹ comprises halogen atoms, lower alkoxy groups as defined in claim 1 and halogeno lower alkoxy groups as defined in claim 1;

said Substituent group β

¹ comprises a group of formula —

NR^cR^d wherein one of R^c and R^d is selected from the group consisting of hydrogen atoms and lower alkyl groups as defined in claim 1 and the other is selected from the group consisting of hydrogen atoms, lower alkyl groups as defined in claim 1 and aralkyl groups as defined in claim 1;

said Substituent group γ

¹ comprises lower alkyl groups as defined in claim 1 which are substituted with a substituent selected from the group consisting of amino groups, amino groups substituted with one or two lower alkyl groups as defined in claim 1 and amino groups substituted with an aralkyl group as defined in claim 1;

and

said Substituent group δ

¹ comprises lower alkyl groups as defined in claim 1, halogeno lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one halogen atom, hydroxy lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one hydroxy group and nitro lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one nitro group.

15. A compound of formula (I) according to claim 1 or a pharmacologically acceptable salt or ester thereof, wherein:

R¹ is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of Substituent group α

¹ defined below, Substituent group β

¹ defined below, Substituent group γ

¹ defined below and Substituent group δ

¹ defined below;

R² is a 4-pyridyl or 4-pyrimidinyl group which optionally is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

; and

in R³, E represents a group of formula >

NR¹⁰ wherein R¹⁰ is as defined in claim 1 and D represents a group of formula >

CR¹¹R¹² wherein R¹¹ and R¹² are as defined in claim 1;

said Substituent group α

¹ comprises halogen atoms, lower alkoxy groups as defined in claim 1 and halogeno lower alkoxy groups as defined in claim 1;

said Substituent group β

¹ comprises a group consisting of a group of formula —

NR^cR^d wherein one of R^c and R^d is selected from the group consisting of hydrogen atoms and lower alkyl groups as defined in claim 1 and the other is selected from the group consisting of hydrogen atoms, lower alkyl groups as defined in claim 1 and aralkyl groups as defined in claim 1;

said Substituent group γ

¹ is selected from the group consisting of lower alkyl groups as defined in claim 1 which are substituted with a substituent selected from the group consisting of amino groups, amino groups substituted with one or two lower alkyl groups as defined in claim 1 and amino groups substituted with an aralkyl group as defined in claim 1;

and

said Substituent group δ

¹ is selected from the group consisting of lower alkyl groups as defined in claim 1, halogeno lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one halogen atom, hydroxy lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one hydroxy group and nitro lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one nitro group.

16. A compound of formula (I) according to claim 1 or a pharmacologically acceptable salt or ester thereof, wherein:

R¹ is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups comprising lower alkyl groups as defined in claim 1 which are substituted with at least one halogen atom and halogeno lower alkoxy groups as defined in claim 1;

R² is a 4-pyridyl or 4-pyrimidinyl group which optionally is substituted at the 2-position thereof with a substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

; and

in R³, one of R⁵ and R⁷ together with R⁶ represents a single bond and the other represents a substituent selected from the group consisting of hydrogen atoms, Substituent group α

, Substituent group γ and

Substituent group δ

;

R⁸, R⁹ and R¹² are the same or different from one another and each represents a substituent selected from the group consisting of hydrogen atoms, Substituent group α

, Substituent group γ and

Substituent group δ

; and

R¹⁰ and R¹¹ are the same or different from one another and each represents a substituent selected from the group consisting of hydrogen atoms, Substituent group α

, Substituent group γ and

Substituent group δ

;

or R¹⁰ and R¹¹ together form an alkylene group having from 1 to 6 carbon atoms which is unsubstituted or is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

.

17. A compound of formula (I) according to claim 1 or a pharmacologically acceptable salt or ester thereof, wherein:

R¹ is selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups;

R² is a 4-pyridyl or 4-pyrimidinyl group which optionally is substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino and α

-methylbenzylamino groups; and

in R³, R¹⁰ and R¹¹ together form a straight chain alkylene group having 3 or 4 carbon atoms which is unsubstituted or is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

.

18. A compound of formula (I) according to claim 1 or a pharmacologically acceptable salt or ester thereof, wherein:

R¹ is selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups;

R² is a 4-pyridyl or 4-pyrimidinyl group which optionally is substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino and α

-methylbenzylamino groups; and

in R³, each of R⁷, R⁸ and R⁹ is a hydrogen atom; and

R¹⁰ and R¹¹ together form a straight chain alkylene group having 3 or 4 carbon atoms which is unsubstituted or is substituted with at least one substituent selected from the group consisting of Substituent group α

, Substituent group β

, Substituent group γ and

Substituent group δ

.

19. A compound of formula (I) according to any one of claims 14 to 18 or a pharmacologically acceptable salt or ester thereof, wherein said compound of formula (I) is a compound of formula (I-1) or (I-3) below:

21. A compound [of formula (I) according to claim 1] selected from the following group of compounds, or a pharmacologically acceptable salt thereof:

2-(4-fluorophenyl)-3-(pyridin-4-yl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(6-methyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1-isopropyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1-propyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1-phenethyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1,2-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1-ethyl-6-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1-ethyl-2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(6-methyl-1-propyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(2-methyl-1-propyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,3,4,6,7,9a-hexahydro-2H-quinolizin-8-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(3,4-difluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole, and

4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole.

22. A compound according to claim 1, which is 2-(4-fluorophenyl-4-(1-phenethyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole, or a pharmacologically acceptable salt thereof.

23. A compound according to claim 1, which is 2-(4-fluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole, or a pharmacologically acceptable salt thereof.

24. A compound according to claim 1, which is 2-(4-fluorophenyl)-4-(6-methyl-1-propyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole, or a pharmacologically acceptable salt thereof

25. A compound according to claim 1, which is 2-(4-fluorophenyl)-4-(2-methyl-1-propyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole, or a pharmacologically acceptable salt thereof.

26. A compound according to claim 1, which is 2-(4-fluorophenyl)-4-(1,3,4,6,7,9a-hexahydro-2H-quinolizin-8-yl)-3-(pyridin-4-yl)-1H-pyrrole, or a pharmacologically acceptable salt thereof.

27. A compound according to claim 1, which is 2-(3,4-difluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole, or a pharmacologically acceptable salt thereof.

28. A compound according to claim 1, which is 4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole, or a pharmacologically acceptable salt thereof.

29. A pharmaceutical composition comprising an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a pharmacologically active compound together with a carrier therefor, wherein said pharmacologically active compound is a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to any one of claims 1 to 12.

30. A pharmaceutical composition comprising an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a pharmacologically active compound together with a carrier therefor, wherein said pharmacologically active compound is a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to claim 13.

31. A pharmaceutical composition comprising an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a pharmacologically active compound together with a carrier therefor, wherein said pharmacologically active compound is a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to any one of claims 15 to 18.

32. A pharmaceutical composition comprising an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a pharmacologically active compound together with a carrier therefor, wherein said pharmacologically active compound is a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to claim 19.

34. A method for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human which comprises administering to a human in need thereof an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to any one of claims 1 to 12.

35. A method for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human which comprises administering to a human in need thereof an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to claim 13.

36. A method for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human which comprises administering to a human in need thereof an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to any one of claims 15 to 18.

37. A method for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human which comprises administering to a human in need thereof an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to claim 19.

39. A method according to claim 34 for inhibiting bone absorption.

41. A method according to claim 34 for the treatment of an inflammatory disease.

43. A method according to claim 34 for the treatment of a viral disease.

45. A method according to claim 34 for relieving pain or pyrexia.

47. A method according to claim 34 for the treatment of chronic rheumatoid arthritis.

49. A method according to claim 34 for the treatment of osteoarthritis.

51. A method according to claim 34 for the treatment of hepatitis.

53. A method according to claim 34 for the treatment of a disease selected from the group consisting of an allergic disease, septicaemia, psoriasis, osteoporosis, ulcerative colitis, diabetes, nephritis, ischemic heart disease, Alzheimer'"'"'s disease and arteriosclerosis.

55. A method of inhibiting the production of an inflammatory cytokine in a human which comprises administering to a human a pharmaceutically effective amount of a compound as defined in any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12.

20. A compound selected from the following group of compounds, or a pharmacologically acceptable salt or ester thereof:

4-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-3-(pyridin-4-yl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-3-(pyridin-4-yl)-4-(1,2,3,6-tetrahydro-2,2,6,6-tetramethylpyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(6-methyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1-ethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1-isopropyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1-propyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1-phenethyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1,6-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1,2-dimethyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,2,2,6,6-pentamethyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(3-dimethylamino-1-propen-1-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(4-aminobutyl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1-ethyl-6-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1-ethyl-2-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(6-allyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(2-allyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(6-benzyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(2-benzyl-1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(6-methyl-1-propyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(2-methyl-1-propyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,3,4,6,7,9a-hexahydro-2H-quinolizin-8-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,3,4,6,9,9a-hexahydro-2H-quinolizin-8-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(2-methylaminopyrimidin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(2-methylaminopyrimidin-4-yl)-1H-pyrrole,

2-(3,4-difluorophenyl)-4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(3,4-difluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

2-(3-fluorophenyl)-4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-3-(pyridin-4-yl)-1H-pyrrole,

4-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-2-phenyl-3-(pyridin-4-yl)-1H-pyrrole, and

4-(1,2,3,5,6,8a-hexahydroindolizin-7-yl)-2-phenyl-3-(pyridin-4-yl)-1H-pyrrole.

33. A pharmaceutical composition comprising an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a pharmacologically active compound together with a carrier therefor, wherein said pharmacologically active compound is a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to any one of claims 20 to 28.

38. A method for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human which comprises administering to a human in need thereof an effective amount for the treatment of a disease which is treatable by inhibiting the production of an inflammatory cytokine in a human of a compound of formula (I) or a pharmacologically acceptable salt, ester or other derivative thereof according to any one of claims 20 to 28.

40. A method according to claim 38 for inhibiting bone absorption.

42. A method according to claim 38 for the treatment of an inflammatory disease.

44. A method according to claim 38 for the treatment of a viral disease.

46. A method according to claim 38 for relieving pain or pyrexia.

48. A method according to claim 38 for the treatment of chronic rheumatoid arthritis.

50. A method according to claim 38 for the treatment of osteoarthritis.

52. A method according to claim 38 for the treatment of hepatitis.

54. A method according to claim 38 for the treatment of a disease selected from the group consisting of an allergic disease, septicaemia, psoriasis, osteoporosis, ulcerative colitis, diabetes, nephritis, ischemic heart disease, Alzheimer'"'"'s disease and arteriosclerosis.

56. A compound of formula (I)′

, or a pharmacologically acceptable salt, ester or other derivative thereof;

57. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^1′

is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of Substituent group α

^1′

defined below and Substituent group β

^1′

defined below;

said Substituent group α

^1′

is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group;

said Substituent group β

^′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower alkyl groups and aralkylamino lower alkyl groups.

58. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^1′

is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups and halogeno lower alkoxy groups.

59. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups.

60. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

61. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

62. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino, and α

-methylbenzylamino groups.

63. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein B′

optionally has one further ring heteroatom or ring group selected from the group consisting of a nitrogen atom, oxygen atom, sulfur atom, >

SO and >

SO₂, said ring is saturated or unsaturated and optionally is fused with an aryl group, a heteroaryl group, a cycloalkyl group or a heterocyclyl group.

64. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein B′

is saturated or unsaturated and optionally is fused with an aryl group, a heteroaryl group, a cycloalkyl group or a heterocyclyl group.

65. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein B′

is a pyrrolidinyl ring or a pyrrolinyl ring.

66. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^3′

is a group of formula (IIa)′

or formula (IIb)′

.

67. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^3′

is a group of formula (IIa)′

.

68. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^4′

is 1 or 2 substituents which are selected independently from the group consisting of said Substituent group α

, said Substituent group β

′ and

Substituent group γ

′

, wherein said Substituent group γ

′

is selected from the group consisting of oxo groups, hydroxyimino groups, lower alkoxyimino groups, lower alkylene groups, lower alkylenedioxy groups, lower alkylsulfinyl groups, lower alkylsulfonyl groups and aryl groups which optionally are substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

69. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups optionally substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

70. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^4′

is a substituent selected from the group consisting of hydroxy groups, fluorine atoms, chlorine atoms, methoxy groups, ethoxy groups, propoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups which is optionally substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

as defined in claim 56.

71. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^4′

is a substituent selected from the group consisting of methoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups.

72. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^4′

is a substituent selected from the group consisting of aryloxy groups which optionally are substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, alkylidene groups and aralkylidene groups.

73. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

74. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein said compound of formula (I)′

is represented by the formula (I-1)′

or (I-3)′

shown below;

75. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein the compound of formula (I)′

is represented by the formula (I-1)′

below;

76. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is 1 or 2 substituents which are selected independently from the group consisting of said Substituent group α

′

, said Substituent group β

′ and

Substituent group γ

^1′

, wherein said Substituent group γ

^1′

is selected from the group consisting of oxo groups, hydroxyimino groups, lower alkoxyimino groups, lower alkylene groups, lower alkylenedioxy groups, lower alkylsulfinyl groups, lower alkylsulfonyl groups and aryl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

77. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

78. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R¹ is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of Substituent group α

^1′

defined below and Substituent group β

^1′

defined below;

said Substituent group α

^1′

is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group;

said Substituent group β

^1′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower atkyl groups and aralkylamino lower alkyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

79. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups and halogeno lower alkoxy groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

; and

R^4′

is a substituent selected from the group consisting of hydroxy groups, fluorine atoms, chlorine atoms, methoxy groups, ethoxy groups, propoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

80. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino, and α

-methylbenzylamino groups;

R^3′

is a group of formula (IIa)′

; and

R^4′

is a substituent selected from the group consisting of methoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups.

81. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of aryloxy groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, alkylidene groups and aralkylidene groups.

82. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of Substituent group α

^1′

defined below and Substituent group β

^1′

defined below,

said Substituent group α

^1′

is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group, and

said Substituent group β

^1′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower alkyl groups and aralkylamino lower alkyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of aryloxy groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

, alkylidene groups and aralkylidene groups.

83. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups and halogeno lower alkoxy groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

, and

R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

84. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein:

R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino, and α

-methylbenzylamino groups;

R^3′

is a group of formula (IIa)′

, and

R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

85. A compound according to any one of claims 76, 77, 78, 79, 80, 81, 82, 83 or 84 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein the compound of formula (I)′

is a compound of formula (I-1)′

or (I-3)′

shown below;

86. A compound according to any one of claims 76, 77, 78, 79, 80, 81, 82, 83 or 84 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein the compound of formula (I)′

is a compound of formula (I-1)′

shown below;

87. A compound according to claim 56 or a pharmacologically acceptable salt, ester or other derivative thereof, wherein the compound is selected from the group consisting of

2-(3-fluorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methylidene-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(3-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-ethyl-3,5,6,8a-tetrahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-propyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole, and

2-(4-fluorophenyl)-4-[2-phenyl]-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole.

88. A compound according to claim 56, wherein the compound is 2-(4-fluorophenyl)-4-[(2R,8aS)-2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

89. A compound according to claim 56, wherein the compound is 2-(4-fluorophenyl)-4-[(8aS)-2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

90. A compound according to claim 56, wherein the compound is 2-(4-fluorophenyl)-4-[(8aS)-2-methylidene-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

91. A compound according to claim 56, wherein the compound is 2-(4-fluorophenyl)-4-[(8aS)-2-methyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

92. A compound according to claim 56, wherein the compound is 4-[(2S,8aS)-2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

93. A compound according to claim 56, wherein the compound is 2-(4-fluorophenyl)-4-[(2S,8aS)-2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

94. A compound according to claim 56, wherein the compound is 2-(4-fluorophenyl)-4-[(2R,8aS)-2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H pyrrole.

95. A pharmaceutical composition comprising an effective amount of a pharmacologically active compound together with a carrier therefor, wherein said pharmacologically active compound is a compound of formula (I)′

or a pharmacologically acceptable salt, ester or other derivative thereof;

96. A pharmaceutical composition according to claim 95, wherein R^1′

is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of Substituent group α

^1′

defined below and Substituent group β

^1′

defined below;

said Substituent group α

^1′

is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group;

said Substituent group β

^1′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower alkyl groups and aralkylamino lower alkyl groups.

97. A pharmaceutical composition according to claim 95, wherein R^1′

is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl and halogeno lower alkoxy groups.

98. A pharmaceutical composition according to claim 95, wherein R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups.

99. A pharmaceutical composition according to claim 95, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

100. A pharmaceutical composition according to claim 95, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

101. A pharmaceutical composition according to claim 95, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino, and α

-methylbenzylamino groups.

102. A pharmaceutical composition according to claim 95, wherein B′

optionally has one further ring heteroatom or ring group selected from the group consisting of a nitrogen atom, oxygen atom, sulfur atom, >

SO and >

SO₂, said ring is saturated or unsaturated and optionally is fused with an aryl group, a heteroaryl group, a cycloalkyl group or a heterocyclyl group.

103. A pharmaceutical composition according to claim 95, wherein B′

is saturated or unsaturated and optionally is fused with an aryl group, a heteroaryl group, a cycloalkyl group or a heterocyclyl group.

104. A pharmaceutical composition according to claim 95, wherein B′

is a pyrrolidinyl ring or a pyrrolinyl ring.

105. A pharmaceutical composition according to claim 95, wherein R^3′

is a group of formula (IIa)′

or formula (IIb)′

.

106. A pharmaceutical composition according to claim 95, wherein R^3′

is a group of formula (IIa)′

.

107. A pharmaceutical composition according to claim 95, wherein R^4′

is 1 or 2 substituents which are independently selected from the group consisting of said Substituent group α

′

, said Substituent group β

′ and

Substituent group γ

^1′

, wherein said Substituent group γ

^1′

is selected from the group consisting of oxo groups, hydroxyimino groups, lower alkoxyimino groups, lower alkylene groups, lower alkylenedioxy groups, lower alkylsulfinyl groups, lower alkylsulfonyl groups and aryl groups which optionally are substituted with at least one substituent selected from the group consisting of Substituent group α

′ and

Substituent group β

′

.

108. A pharmaceutical composition according to claim 95, wherein R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups optionally substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

109. A pharmaceutical composition according to claim 95, wherein R^4′

is a substituent selected from the group consisting of hydroxy groups, fluorine atoms, chlorine atoms, methoxy groups, ethoxy groups, propoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups which optionally is substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

110. A pharmaceutical composition according to claim 95, wherein R^4′

is a substituent selected from the group consisting of methoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups.

111. A pharmaceutical composition according to claim 95, wherein R^4′

is a substituent selected from the group consisting of aryloxy groups which optionally are substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

, alkylidene groups and aralkylidene groups.

112. A pharmaceutical composition according to claim 95, wherein R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

113. A pharmaceutical composition according to claim 95, wherein said compound of formula (I)′

is represented by the formula (I-1)′

or (I-3)′

shown below;

114. A pharmaceutical composition according to claim 95, wherein the compound of formula (I)′

is represented by the formula (I-1)′

below;

115. A pharmaceutical composition according to claim 95, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is 1 or 2 substituents which are independently selected from the group consisting of said Substituent group α

, said Substituent group β and

Substituent group γ

^1′

, wherein said Substituent group γ

^1′

is selected from the group consisting of oxo groups, hydroxyimino groups, lower alkoxyimino groups, lower alkylene groups, lower alkylenedioxy groups, lower alkylsulfinyl groups, lower alkylsulfonyl groups and aryl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

116. A pharmaceutical composition according to claim 95, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

117. A pharmaceutical composition according to claim 95, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of Substituent group α

^1′

defined below and Substituent group β

^1′

defined below;

R^3′

is a group of formula (IIa)′

or formula (IIb)′

;

said Substituent group α

^1′

is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group;

said Substituent group β

^1′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower alkyl groups and aralkylamino lower alkyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

; and

R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups, which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

118. A pharmaceutical composition according to claim 95, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups and halogeno lower alkoxy groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

; and

R^3′

is a group of formula (IIa)′

;

R^4′

is a substituent selected from the group consisting of hydroxy groups, fluorine atoms, chlorine atoms, methoxy groups, ethoxy groups, propoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

119. A pharmaceutical composition according to claim 95, wherein:

R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino, and a-methylbenzylamino groups; and

R^3′

is a group of formula (IIa)′

;

R^4′

is a substituent selected from the group consisting of methoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups.

120. A pharmaceutical composition according to claim 95, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of aryloxy groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, alkylidene groups and aralkylidene groups.

121. A pharmaceutical composition according to claim 95, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of Substituent group α

^1′

defined below and Substituent group β

^1′

defined below,

said Substituent group ax is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group, and

said Substituent group β

^1′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower alkyl groups and aralkylamino lower alkyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of aryloxy groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, alkylidene groups and aralkylidene groups.

122. A pharmaceutical composition according to claim 95, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups and halogeno lower alkoxy groups;

R^2′

is a 4-pyridyl or 4-pyriridinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

; and

R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

123. A pharmaceutical composition according to claim 95, wherein:

R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino, and α

-methylbenzylamino groups;

R^3′

is a group of formula (IIa)′

; and

R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

124. A pharmaceutical composition according to any one of claims 115, 116, 117, 118, 119, 120, 121, 122 or 123, wherein the compound of formula (I)′

is a compound of formula (I-1)′

or (I-3)′

shown below;

125. A pharmaceutical composition according to any one of claims 115, 116, 117, 118, 119, 120, 121, 122 or 123, wherein the compound of formula (I)′

is a compound of formula (I-1)′

;

126. A pharmaceutical composition according to claim 95, wherein the compound of formula (I)′

is selected from the group consisting of

2-(3-fluorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-phenyl-1,2,3,5,6, 8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl) 1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methylidene-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(3-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-ethyl-3,5,6,8a-tetrahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-propyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole, and

2-(4-fluorophenyl)-4-[2-phenyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole, or a pharmacologically acceptable salt, ester or other derivative thereof.

127. A composition according to claim 95, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(2R,8aS)-2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

128. A composition according to claim 95, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(8aS)-2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

129. A composition according to claim 95, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(8aS)-2-methylidene-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H- or a pharmacologically acceptable salt, ester or other derivative thereof.

130. A composition according to claim 95, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(8aS)-2-methyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

131. A composition according to claim 95, wherein said compound of formula (I)′

is selected from 4-[(2S,8aS)-2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

132. A composition according to claim 95, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(2S,8aS)-2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

133. A composition according to claim 95, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(2R,8aS)-2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

190. (New) A pharmaceutical composition according to claim 95, wherein said composition is for the treatment or prophylaxis of septicemia.

134. A method for the treatment or prophylaxis of a disease treatable or preventable by inhibiting the production of an inflammatory cytokine in a mammal which comprises administering to said mammal an effective amount of a compound of formula (I)′

or a pharmacologically acceptable salt, ester or other derivative thereof;

135. A method according to claim 134, wherein the mammal is a human.

136. A method according to claim 135, wherein R^1′

is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of Substituent group α

^1′

defined below and Substituent group β

^1′

defined below;

said Substituent group al is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group;

said Substituent group β

^1′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower alkyl groups and aralkylamino lower alkyl groups.

137. A method according to claim 135, wherein R^1′

is a phenyl group which optionally is substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups and halogeno lower alkoxy groups.

138. A method according to claim 135, wherein R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups.

139. A method according to claim 135, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

140. A method according to claim 135, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

141. A method according to claim 135, wherein R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups optionally being substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino, and a-methylbenzylamino groups.

142. A method according to claim 135, wherein B′

optionally has one further ring heteroatom or ring group selected from the group consisting of a nitrogen atom, oxygen atom, sulfur atom, >

SO and >

SO₂, said ring may be saturated or unsaturated and optionally is fused with an aryl group, a heteroaryl group, a cycloalkyl group or a heterocyclyl group.

143. A method according to claim 135, wherein B′

is saturated or unsaturated and optionally is fused with an aryl group, a heteroaryl group, a cycloalkyl group or a heterocyclyl group.

144. A method according to claim 135, wherein B′

is a pyrrolidinyl ring or a pyrrolinyl ring.

145. A method according to claim 135, wherein R^3′

is a group of formula (IIa)′

or I formula (IIb)′

.

146. A method according to claim 135, wherein R^3′

is a group of formula (IIa)′

.

147. A method according to claim 135, wherein R^4′

is 1 or 2 substituents which are independently selected from the group consisting of said Substituent group α

′

, Substituent group β

′ and

Substituent group γ

^1′

, wherein said Substituent group γ

^1′

is selected from the group consisting of oxo groups, hydroxyimino groups, lower alkoxyimino groups, lower alkylene groups, lower alkylenedioxy groups, lower alkylsulfinyl groups, lower alkylsulfonyl groups and aryl groups which optionally are substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

.

148. A method according to claim 135, wherein R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups optionally substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

149. A method according to claim 135, wherein R^4′

is a substituent selected from the group consisting of hydroxy groups, fluorine atoms, chlorine atoms, methoxy groups, ethoxy groups, propoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups which optionally are substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

150. A method according to claim 135, wherein R^4′

is a substituent selected from the group consisting of methoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups.

151. A method according to claim 135, wherein R^4′

is a substituent selected from the group consisting of aryloxy groups which optionally are substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, alkylidene groups and aralkylidene groups.

152. A method according to claim 135, wherein R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

153. A method according to claim 135, wherein said compound of formula (I)′

is represented by the formula (I-1)′

or (I-3)′

shown below;

154. A method according to claim 135, wherein the compound of formula (I)′

is represented by the formula (I-1)′

below;

155. A method according to claim 135, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is 1 or 2 substituents which are independently selected from the group consisting of said Substituent group α

′

, said Substituent group β and

Substituent group γ

^1′

, wherein said Substituent group γ

^1′

is selected from the group consisting of oxo groups, hydroxyimiro groups, lower alkoxyimino groups, lower alkylene groups, lower alkylenedioxy groups, lower alkylsulfinyl groups, lower alkylsulfonyl groups and aryl groups which are unsubstituted or substituted with at least one substituent selected from Substituent group α

′ and

said Substituent group β

′

.

156. A method according to claim 135, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

157. A method according to claim 135, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of Substituent group α

^1′

defined below and Substituent group β

^1′

defined below;

said Substituent group α

^1′

is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group;

said Substituent group β

^1′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower alkyl groups and aralkylamino lower alkyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

on formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of hydroxy groups, halogen atoms, lower alkoxy groups, lower alkylthio groups, halogeno lower alkoxy groups, lower alkyl groups, halogeno lower alkyl groups, oxo groups, aryl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′

, said Substituent group β

′

, lower alkylenedioxy groups, lower alkylene groups and lower alkylsulfonyl groups.

158. A method according to claim 135, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups and halogeno lower alkoxy groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

; and

R^4′

is a substituent selected from the group consisting of hydroxy groups, fluorine atoms, chlorine atoms, methoxy groups, ethoxy groups, propoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

.

159. A method according to claim 135, wherein:

R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino and x-methylbenzylamino groups;

R^3′

is a group of formula (IIa)′

; and

R^4′

is a substituent selected from the group consisting of methoxy groups, methyl groups, ethyl groups, propyl groups and phenyl groups.

160. A method according to claim 135, wherein:

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of aryloxy groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

^1′

, said Substituent group β

^1′

alkylidene groups and aralkylidene groups.

161. A method according to claim 135, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from Substituent group α

^1′

defined below and Substituent group defined below,

said Substituent group α

^1′

is selected from the group consisting of halogen atoms, lower alkoxy groups, halogeno lower alkoxy groups and groups of formula —

NR^a′

R^b′

, wherein one of R^a′

and R^b′

0 represents a hydrogen atom or a lower alkyl group, and the other represents a hydrogen atom, a lower alkyl group or an aralkyl group,

said Substituent group β

^1′

is selected from the group consisting of lower alkyl groups, halogeno lower alkyl groups, hydroxyl lower alkyl groups, nitro lower alkyl groups, amino lower alkyl groups, lower alkylamino lower alkyl groups, di(lower alkyl)amino lower alkyl groups and aralkylamino lower alkyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

;

R^3′

is a group of formula (IIa)′

or formula (IIb)′

; and

R^4′

is a substituent selected from the group consisting of aryloxy groups which are unsubstituted or substituted with at least one substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

, alkylidene groups and aralkylidene groups.

162. A method according to claim 135, wherein:

R^1′

is a phenyl group which is unsubstituted or substituted with at least one substituent selected from the group consisting of halogen atoms, halogeno lower alkyl groups and halogeno lower alkoxy groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of said Substituent group α

′ and

said Substituent group β

′

; and

R^3′

is a group of formula (IIa)′

; and

R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

163. A method according to claim 135, wherein:

R^1′

is a substituent selected from the group consisting of phenyl, 4-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3,4-difluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-4-fluorophenyl, 3-difluoromethoxyphenyl and 3-trifluoromethylphenyl groups;

R^2′

is a 4-pyridyl or 4-pyrimidinyl group, said groups being unsubstituted or substituted at the 2-position thereof with a substituent selected from the group consisting of methoxy, amino, methylamino, benzylamino, and α

-methylbenzylamino groups;

R^3′

is a group of formula (IIa)′

; and

R^4′

is a substituent selected from the group consisting of phenoxy, methylidene, ethylidene, propylidene and benzylidene groups.

164. A method according to claim 135, wherein the compound of formula (I)′

is selected from the group consisting of

2-(3-fluorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-methylidene-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(3-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-fluorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

2-(3-chlorophenyl)-4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole,

4-[2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-2-(3-trifluoromethylphenyl)-1H-pyrrole,

4-[2-ethyl-3,5,6,8a-tetrahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole,

2-(4-fluorophenyl)-4-[2-propyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole, and

2-(4-fluorophenyl)-4-[2-phenyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole, or a pharmaceutically acceptable salt, ester or other derivative thereof.

165. A method according to claim 135, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(2R,8aS)-2-phenyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

166. A method according to claim 135, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(8aS)-2-methyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

167. A method according to claim 135, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(8aS)-2-methylidene-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

168. A method according to claim 135, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(8aS)-2-methyl-3,5,6,8a-tetrahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

169. A method according to claim 135, wherein said compound of formula (I)′

is selected from 4-[(2S,8aS)-2-ethyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-2-(4-fluorophenyl)-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

170. A method according to claim 135, wherein said compound of formula (I)′

is selected from 2-(4-fluorophenyl)-4-[(2S,8aS)-2-propyl-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole or a pharmacologically acceptable salt, ester or other derivative thereof.

171. A method according to claim 135, wherein the compound is 2-(4-fluorophenyl)-4-[(2R,8aS)-2-methoxy-1,2,3,5,6,8a-hexahydroindolizin-7-yl]-3-(pyridin-4-yl)-1H-pyrrole.

172. A method according to any one of claims 150 to 158, wherein the compound of formula (I)′

is a compound of formula (I-1)′

or (I-3)′

shown below;

173. A method according to any one of claims 155 to 163, wherein the comound of formula (I)′

is a compound of formula (I-1)′

shown below;

174. A method according to any one of claims 134 to 171, wherein the method is for inhibiting bone resporption, relieving inflammation, treating or preventing a viral disease, relieving pain or pyrexia, treating or preventing chronic rheumatoid arthritis, treating or preventing osteoarthritis, treating or preventing cancer or treating or preventing hepatitis.

175. A method according to claim 135, wherein said method is for inhibiting bone resorption.

176. A method according to claim 135, wherein said method is for relieving inflammation.

177. A method according to claim 135, wherein said method is for the treatment or prophylaxis of a viral disease.

178. A method according to claim 135, wherein said method is for relieving pain or pyrexia.

179. A method according to claim 135, wherein said method is for the treatment or prophylaxis of chronic rheumatoid arthritis.

180. A method according to claim 135, wherein said method is for the treatment or prophylaxis of osteoarthritis.

181. A method according to claim 135, wherein said method is for the treatment or prophylaxis of cancer.

182. A method according to claim 135, wherein said method is for the treatment or prophylaxis of hepatitis.

183. A method according to claim 135, wherein said method is for the treatment or prophylaxis of asthma.

184. A method according to claim 135, which is for treatment of said disease.

185. A method according to claim 135, which is for preventing said disease.

186. A method according to any one of claims 134 to 171, wherein said method is for the treatment or prophylaxis of a disease selected from the group consisting of an allergic disease, septicaemia, psoriasis, degenerative arthritis, Crohn'"'"'s disease, systemic lupus erythematosus, osteoporosis, ulcerative colitis, diabetes, nephritis, ischemic heart disease, Alzeimer'"'"'s disease and arteriosclerosis.

189. (New) A method according to claim 188, wherein the method is for the treatment of septicemia.