Note: Claims are shown in the official language in which they were submitted.
The embodiments of the invention in which an
exclusive property or privilege is claimed are defined as
follows:
1. A process for preparing an imidazole derivative of
the formula (I)
<IMG> (I)
wherein each of R1 and R4 is a hydrogen atom or a lower
alkyl group; each of R2 and R3 is a hydrogen atom, a halogen
atom, a hydroxyl group, a lower alkyl group, a lower alkoxy
group, an aralkyloxy group, a nitro group or an amino group;
A is -O-, -S-, -CH=CH- or -CH=N-, Z is an aryl group, a
thienyl group; a pyridyl group or a furyl group, in which
definition these aromatic (heterocyclic) rings may have 1 to
3 substituents, each substituent being independently
selected from a halogen atom, a lower alkyl group, a cyclic
alkyl group, a lower alkoxy group, a hydroxyl group, a
carboxyl group, a lower alkoxycarbonyl group, a carboxy-
lower-alkoxy group, a di-lower-alkylamino-lower-alkoxy group
and a nitro group, or a pharmaceutically acceptable acid
23
Claim 1 continued...
addition salt thereof, comprising a process selected from
the group of processes comprising:
(a) a process for preparing an imidazole
derivative of the formula (I) above or a pharmaceutically
acceptable acid addition salt thereof, wherein each of R1,
R2, R3, R4, A and Z is as defined above which comprises
reacting a compound of the formula:
<IMG>
with an organometallic compound of the formula:
ZMgX or ZLi
wherein R1, R2, R3, R4, A and Z are as defined above and X
is a halogen atom;
(b) a process for preparing an imidazole
derivative of the formula (I) above, or a pharmaceutically
acceptable acid addition salt thereof, wherein each of
24
Claim 1 (b) continued...
R1, R2, R3, A and Z is as defined above and R4 is hydrogen
which comprises subjecting to reduction a compound of the
formula:
<IMG>
wherein R1, R2, R3, A and Z are as defined above, and
(c) a process for preparing an imidazole derivative
of the formula (I) above, or a pharmaceutically acceptable
acid addition salt thereof, wherein each of R1, R2, R3, A
and Z are as defined above and R4 is a lower alkyl group,
which comprises reacting a compound of the formula:
<IMG>
Claim 1 (c) continued...
wherein R1, R2, R3, A and Z are as defined above with a
compound of the formula:
R5MgX
wherein R5 is a lower alkyl group.
2. An imidazole derivative of the formula:
<IMG>
wherein each of R1 and R4 is a hydrogen atom or a lower
alkyl group; each of R2 and R3 is a hydrogen atom, a halogen
atom, a hydroxyl group, a lower alkyl group, a lower alkoxy
group, an aralkyloxy group, a nitro group or an amino group;
A is -O-, -S-, -CH=CH- or -CH=N-; Z is an aryl group, a
thienyl group; a pyridyl group or a furyl group, in which
definition these aromatic (heterocyclic) rings may have
1 to 3 substituents, each substituent being independently
selected from a halogen atom, a lower alkyl group, a cyclic
alkyl group, a lower alkoxy group, a hydroxyl group, a
26
Claim 2 continued...
carboxyl group, a lower alkoxycarbonyl group, a carboxy-
lower-alkoxy group, a di-lower-alkylamino-lower-alkoxy group
and a nitro group, or a pharmaceutically acceptable acid
addition salt thereof, when prepared by the process of
claim 1 or an obvious chemical equivalent.
3. Process (a) of claim 1.
4. The imidazole derivative claimed in claim 2 when
prepared by the process of claim 3 or an obvious chemical
equivalent.
5. Process (b) of claim 1.
6. The imidazole derivative claimed in claim 2 wherein
R4 is hydrogen when prepared by the process of claim 5 or an
obvious chemical equivalent.
7. Process (c) of claim 1.
8. The imidazole derivative claimed in claim 2 wherein
R4 is a lower alkyl group when prepared by the process of
claim 7 or an obvious chemical equivalent.
9. A process for preparing ?-(2,4,6-trimethylphenyl)-
3-chloro-4-(1-imidazolyl)benzenemethanol which comprises
subjecting 3-chloro-4-(1-imidazolyl)-2',4',6-
trimethylbenzophenone to reduction with sodium borohydride.
27
10. ?-(2,4,6-Trimethylphenyl)-3-chloro-4-(1-
imidazolyl)benzenemethanol when prepared by the process of
claim 9 or an obvious chemical equivalent.
11. A process of preparing ?-(2,4,6-trimethylphenyl)-3-
(1-imidazolyl)benzenemethanol which comprises subjecting 3-
(1-imdazolyl)-2',4',6'-trimethylbenzophenone to reduction
with sodium borohydride.
12. ?-(2,4,6-Trimethylphenyl)-3-(1-imidazolyl)-
benzenemethanol when prepared by the process of claim 11 or
an obvious chemical equivalent.
13. A process for preparing ?-(2,4,6-trimethylphenyl)-
2-methyl-3-(1-imidazolyl)benzenemethanol which comprises
reacting 2-methyl-3-(1-imidazolyl)-benzaldehyde with 2,4,6-
trimethylphenylmagnesium bromide.
14. ?-(2,4,6-Trimethylphenyl)-2-methyl-3-(1-
imidazolyl)benzenemethanol when prepared by the process of
claim 13 or an obvious chemical equivalent.
15. A process for preparing ?-(2,4,6-trimethylphenyl)-
4-methyl-3-(1-imidazolyl)benzenemethanol which comprises
subjecting 4-methyl-3-(1-imidazolyl)-2',4',6'-
trimethylphenyl benzophenone to reduction with sodium
borohydride.
28
16. ?-(2,4,6-Trimethylphenyl)-4-methyl-3-(1-
imidazolyl)benzenemethanol when prepared by the process of
claim 15 or an obvious chemical equivalent.
17. A process for preparing ?-(2,4,6-trimethylphenyl)-
2-chloro-5-(1-imidazolyl)benzenemethabol which comprises
subjecting 2-chloro-5-(1-imidazolyl)-2,4,6-trimethylphenyl
benzophenone to reduction with sodium borohydride.
18. ?-(2,4,6-Trimethylphenyl)-2-chloro-5-(1-
imidazolyl)benzenemethabol when prepared by the process of
claim 17 or an obvious chemical equivalent.
19. A process for preparing ?-(2,4,6-trimethylphenyl)-
2-methyl-5-(1-imidazolyl)benzenemethanol which comprises
subjecting 2-methyl-5-(1-imidazolyl)-2',4',6'-
trimethylphenyl benzophenone to reduction with sodium
borohydride.
20. ?-(2,4,6 Trimethylphenyl)-2-methyl-5-(1-
imidazolyl)benzenemethanol when prepared by the process of
claim 19 or an obvious chemical equivalent.
21. A process for preparing ?-(2,4,6-trimethylphenyl)-
2-methoxy-5-(1-imidazolyl)benzenemethanol which comprises
subjecting 2-methoxy-5-(1-imidazolyl)-2',4',6'-
trimethylphenyl benzophenone to reduction with sodium
borohydride.
29
22. ?-(2,4,6-Trimethylphenyl)-2 methoxy-5-(1-
imidazolyl)benzenemethanol when prepared by the process of
claim 21 or an obvious chemical equivalent.
23. A process for preparing ?-(2,4,6-trimethylphenyl)-
3-chloro-5-(1-imidazolyl)benzenemethanol which comprises
reacting 3-chloro-5-(1-imidazolyl)-benzaldehyde with 2,4,6-
trimethylphenylmagnesium bromide.
24. ?-(2,4,6-Trimethylphenyl)-3-chloro-5-(1-
imidazolyl)benzenemethanol when prepared by the process of
claim 23 or an obvious chemical equivalent.
25. A process for preparing ?-(2,4,6-trimethylphenyl)-
2-hydroxy-5-(1-imidazolyl)-benzenemethanol,which comprises
subjecting 2-hydroxy-5-(1-imidazolyl)-2',4',6'-
trimethyphenyl benzophenone to reduction with sodium
borohydride.
26. ?-(2,4,6-Trimethylphenyl)-2-hydroxy-5-(1-
imidazolyl)-benzenemethanol when prepared by the process of
claim 25 or an obvious chemical equivalent.
27. An imidazole derivative of the general formula
(I) as defined in claim 1 and the pharmaceutically
acceptable acid addition salts thereof.
28. An imidazole derivative of the general formula
(I) as defined in claim 1 wherein R4 is hydrogen, and
the pharmaceutically acceptable acid addition salts
thereof.
29. An imidazole derivative of the general formula
(I) as defined in claim 1 wherein R4 is a lower alkyl
group and the pharmaceutically acceptable acid addition
salts thereof.
30. ?-(2,4,6-Trimethylphenyl)-3-chloro-4-(1-
imidazolyl)benzenemthanol.
31. ?-(2,4,6-Trimethylphenyl)-3-(1-imidazolyl)-
benzenemethanol.
32. ?-(2,4,6-Trimethylphenyl)-2-methyl-3-(1-
imidazolyl)benzenemethanol.
31
33. ?-(2,4,6-Trimethylphenyl)-4-methyl-3-(1-
imidazolyl)benzenemethanol.
34. ?-(2,4,6-Trimethylphenyl)-2-chloro-5-(1-
imidazolyl)benzenemethanol.
35. ?-(2,4,6-Trimethylphenyl)-2-methyl-5-(1-
imidazolyl)benzenemethanol.
36. ?-(2,4,6-Trimethylphenyl)-2-methoxy-5-(1-
imidazolyl)benzenemethanol.
37. ?-(2,4,6-Trimethylphenyl)-3-chloro-5-(1-
imidazolyl)benzenemethanol,
38. ?-(2,4,6-Trimethylphenyl)-2-hydroxy-5-(1-
imidazolyl)benzenemethanol.
32