Antiinflammatory and antiallergic imidazole derivatives

Imidazole derivatives of Formula I ##STR1## wherein AR.sub.1 and AR.sub.2 each independently represent phenyl optionally substituted by halogen atoms, alkyl groups, or alkoxy groups, PA0 R.sub.1 is pyrrolyl, indolyl, imidazolyl, or thiazolyl, all of which are optionally substituted by lower alkyl, free or esterified carboxy or carboxyalkyl groups, benzyl, or benezenesulfonyl; and R.sub.2 is hydrogen, lower alkyl, haloalkyl, or a methylene, dimethylene, trimethylene, or tetramethylene group linked to the nitrogen atom of R.sub.1, PA0 and the physiologically acceptable salts thereof with acids, and when R.sub.1 is substituted by carboxy, also the physiologically acceptable salts thereof with bases, PA0 are pharmacologically effective compounds, e.g., as antiinflammatories.

The present invention relates to novel imidazole derivatives, to a process 
for their production, and to pharmaceutical preparations containing them 
as active ingredients. 
SUMMARY OF THE INVENTION 
It is an object of this invention to provide new pharmacologically active 
compounds. 
Upon further study of the specification and appended claims, further 
objects and advantages of this invention will become apparent to those 
skilled in the art. 
These objects have been attained by providing compounds of Formula (I) 
##STR2## 
wherein 
AR.sub.1 and AR.sub.2 each independently represent phenyl optionally 
substituted by halogen atoms, alkyl groups, or alkoxy groups, 
R.sub.1 is pyrrolyl, indolyl, imidazolyl, or thiazolyl, all of which are 
optionally substituted by lower alkyl, free or esterified carboxy or 
carboxyalkyl groups, benzyl, or benzenesulfonyl; and R.sub.2 is hydrogen, 
lower alkyl, haloalkyl, or a methylene, dimethylene, trimethylene, or 
tetramethylene group linked to the nitrogen atom of R.sub.1, 
and the physiologically acceptable salts thereof with acids, and when 
R.sub.1 is substituted by carboxy, also the physiologically acceptable 
salts thereof with bases. 
DETAILED DISCUSSION 
According to this invention, the substituents AR.sub.1 and AR.sub.2 of the 
imidazole derivatives are each independently phenyl optionally substituted 
by halogen atoms (F,Cl,Br), alkyl residues, or alkoxy residues. Usually, 
AR.sub.1 and AR.sub.2 are the same, but this is not necessary. Suitable 
phenyl residues AR.sub.1 and AR.sub.2 substituted by halogen atoms 
include, for example, mono- or difluorophenyl or mono- or dichlorophenyl 
and, in particular, p-fluorophenyl or p-chlorophenyl. Alkyl- substituted 
phenyl includes preferably those wherein the alkyl groups contain 1-4 
carbon atoms (e.g., methyl, ethyl, propyl, isopropyl, and the like). 
Phenyl residues substituted by alkoxy groups include preferably those 
wherein the alkoxy groups contain 1-4 carbon atoms (methoxy, ethoxy, 
propoxy, isopropoxy, etc.). 
The phenyl residues AR.sub.1 and AR.sub.2 can be mono- or polysubstituted 
with identical or different substituents. They are preferably 
monosubstituted, preferably in the 4-position. Especially preferred are 
the substituents wherein AR.sub.1 and AR.sub.2 each is phenyl or phenyl 
substituted in the para-position by fluorine, chlorine or an alkoxy group 
of 1-4 carbon atoms or wherein AR.sub.1 and AR.sub.2 each is phenyl, 
4-fluorophenyl, 4-chlorophenyl, or 4-methoxyphenyl; in particular both or 
at least one is p-methoxyphenyl. 
Preferably, the point of attachment of the R.sub.1 heterocycle is a C-atom, 
e.g., 2-pyrrolyl, 3-pyrrolyl, 2-indole, 3-indole, 2-imidazolyl, 4- or 
5-imidazolyl, or 2, 4- or 5-thiazole. The point of attachment of the 
substituent(s) on the heterocycle can be a C- or N- atom. Lower alkyl 
groups suitable as substituents include those of 1-6 carbon atoms. The 
carboxy-containing substituents can be esterified (COOR) by R groups which 
are C.sub.1-6 -alkyl. 
The carboxyalkyl groups can have alkyl portions of 1-4 C atoms. The R.sub.1 
heterocycle can be mono- or poly-substituted. 
Especially preferred residues R.sub.1 are 2-pyrrolyl, 3-pyrrolyl, 
7-[2,3-dihydro-1H-pyrrolizidyl], 2-indolyl, 2-imidazolyl, or 2-thiazolyl, 
or one of the foregoing substituted by methyl groups or lower 
alkoxycarbonyl groups. 
The substituent R.sub.2 of the imidazole derivatives of this invention can 
be hydrogen or alkyl of 1-6 carbon atoms, optionally substituted by 
halogen (F,Cl,Br,I) (preferably by bromine or iodine), or a methylene, 
dimethylene group, trimethylene group, or tetramethylene group linked to 
the nitrogen atom of R.sub.1. The latter four embodiments produce 
pyrrolizine, pyrrolopyrazine, pyrrolodiazepin and pyrrolodiazocin rings 
fused to the imidazole ring in various orientations. Preferred 
halosubstituted alkyl residues are 2-haloethyl, 3-halopropyl, and 
3-halobutyl. These compounds are preferably used as intermediates for the 
preparation of other compounds of this invention. 
Physiologically acceptable salts of the imidazole derivatives of Formula I 
include, for example, salts of hydrogen chloride, hydrogen bromide, or 
hydrogen iodide, of sulfuric acid, phosphoric acid, and the like or salts 
of organic acids, such as formic acid, acetic acid, succinic acid, maleic 
acid, tartaric acid, or citric acid, etc. 
If the imidazole derivatives of Formula I contain carboxy groups, they can 
form salts for example with alkali metals, such as sodium or potassium, 
etc. 
The novel imidazole derivatives of this invention can be prepared by 
conventional methods. Suitable manufacturing methods include, for example, 
a process comprising condensing a diketone of Formula II 
##STR3## 
wherein AR.sub.1 and AR.sub.2 are as defined above, in the presence of 
ammonium ions, with an aldehyde of Formula III 
##STR4## 
wherein R.sub.1 is as defined above, and the thus-obtained compounds are 
optionally conventionally N-alkylated and/or converted into the salts 
thereof. 
This synthesis can be conducted under conditions known per se. (See, e.g., 
Arnold Weissberger: The Chemistry of Heterocyclic Compounds, Vol. 6: Klaus 
Hoffman: Imidazole an Its Derivatives, Part I--Interscience Publishers 
Inc., New York [1953], pages 34 et seq., which is incorporated by 
reference herein). 
The starting compounds used in this process are all known or can be readily 
prepared in a manner known per se. (See, e.g., Chem. Ber. 113 : 2694 
[1980]; Canad. J. Chem. 56 : 654 [1978]; or J. Chem Soc. 84 : 635 [1962], 
whose disclosures are incorporated by reference herein). 
The imidazole derivatives of this invention are distinguished by a 
pronounced antiinflammatory and antiallergic activity. Moreover, these 
imidazole derivatives are distinguished by a very favorable dissociation 
between desired pharmacological efficaciousness and 
undesirable--especially ulcerogenic--side effects. The antiinflammatory 
activity of the compounds of this invention can be determined with the aid 
of conventional protocols such as the adjuvant arthritis test which is 
conducted as follows: 
Female and male rats of the Lewis strain (LEW) with a weight span of 
110-190 g are utilized. The animals receive drinking water and "Altromin" 
pressed feed ad libitum. 
Ten rats are used for each dosage group. 
Mycobacterium butyricum from Difko, Detroit, is utilized as the irritant. 
The rats were injected in the right hind paw, subplantar, with a 
suspension of 0.5 mg of Mycobacterium butyricum in 0.1 ml of thinly fluid 
paraffin (DAB [German Pharmacopoecial] 7). 
The test compounds are orally administered daily, starting with the 
eleventh day of the trial, over a 4 day period. The compounds are given as 
a clear, aqueous solution or a crystalline suspension with the addition of 
"Myrj" 53 (85 mg %) in an isotonic sodium chloride solution. 
EXPERIMENTAL DESIGN 
The rats are subdivided into groups with maximum uniformity regarding body 
weight. After measuring the volume of the right hind paw by 
plethysmography, 0.1 ml of adjuvant is injected into this paw in a 
subplantar fashion. 
The right hind paws are measured from the 14th day of the trial to the end 
of the test. The duration of the trial is three weeks. 
The dosage is determined at which a 40% decrease in paw volume is obtained 
as compared with the untreated animal (ED.sub.40 in mg/kg body weight). 
The table below shows the results obtained in this test for the compounds 
of this invention, compared with the previously known, structurally 
analogous compound 1 (see DOS No. 2,155,558). 
______________________________________ 
Adjuvant 
Arthritis Test 
Dose 
in mg/kg % Inhibi- 
No. Compound Animal bition 
______________________________________ 
1 4,5-Bis(4-methoxyphenyl)-2-(2- 
4 .times. 10 
12 
thienyl)-imidazole 
2 4,5-Bis(4-methoxyphenyl)-2-(2- 
4 .times. 10 
39 
pyrrolyl)-imidazole 
3 4,5-Bis(4-methoxyphenyl)-2-(4-meth- 
4 .times. 10 
30 
oxy-carbonyl-2-pyrrolyl) imidazole 
4 4,5-Bis(4-fluorophenyl)-2-(2- 
4 .times. 10 
21 
pyrrolyl)-1-(3-bromopropyl)imidazole 
5 7-[4,5-Bis(4-methoxyphenyl)-2-imida- 
4 .times. 10 
31 
zolyl]-2,3-dihydro-1H--pyrrolizine 
6 2,3-Bis(4-methoxyphenyl)-5,6-dihydro- 
4 .times. 10 
25 
imidazo-[1,2-a]pyrrolo[2,1-c]pyazine 
7 2,3-Bis(4-methoxyphenyl)-6,7-dihydro- 
4 .times. 10 
34 
5H--imidazo[1,2-a]pyrrolo-1,4- 
diazepine 
8 2,3-Bis(4-methoxyphenyl)-5,6,7,8- 
4 .times. 10 
20 
tetrahydro-imidazo[1,2-a]pyrrolo- 
[2,1-c]-1,4-diazocine 
______________________________________ 
Consequently, the novel compounds, in combination with the excipients 
customary in galenic pharmacy, are suitable, for example, for the 
treatment of acute or chronic polyarthritis, neurodermitis, bronchial 
asthma, hay fever, and other diseases, in mammals including humans. 
It is furthermore noteworthy that the imidazole derivatives of this 
invention are also suitable for the treatment of migraine and 
dysmenorrhea. 
The medical specialties of this invention can be prepared as usual, by 
converting the active compounds together with suitable additives, 
excipients, and flavoring agents into the desired forms of administration, 
such as tablets, dragees, capsules, solutions, inhalants, etc. 
Especially suitable for oral administration are tablets, dragees, and 
capsules, containing, for example, 1-250 mg of active ingredient and 50 mg 
to 2 g of a pharmacologically inert carrier, such as, for example, 
lactose, amylose, talc, gelatin, magnesium stearate, and similar agents, 
as well as the customary additives. Typically, dosages are 10-500 
mg/kg/day. Precise dosages can be readily determined by conventional 
considerations, e.g., in conjunction with differential potency tests based 
on known agents using conventional protocols. The administration of the 
compounds of this invention is analogous, e.g., to that of the known 
anti-inflammatory effective agent indometacine. 
Without further elaboration, it is believed that one skilled in the art 
can, using the preceding description, utilize the present invention to its 
fullest extent. The following preferred specific embodiments are, 
therefore, to be construed as merely illustrative, and not limitative of 
the remainder of the disclosure in any way whatsoever. In the following 
examples, all temperatures are set forth uncorrected in degrees Celsius; 
unless otherwise indicated, all parts and percentages are by weight.

EXAMPLE 1 
A mixture of 18.7 g of 4,4'-dimethoxybenzil, 10.0 g of 2-formylpyrrole, 
50.0 g of ammonium acetate, and 200 ml of acetic acid are placed, in a 
flask, into an oil bath preheated to 170.degree. C. and stirred for 15 
minutes. Then, under heating, such an amount of water is added that a 
permanent precipitate is produced, and this mixture is then allowed to 
stand overnight. The thus-obtained precipitate is filtered off and 
separated by chromatography on silica gel, eluent hexane/ethyl acetate 
(1:1). Yield: 11.2 g of 4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)imidazole, 
mp 237.degree. C. 
C.sub.21 H.sub.19 N.sub.3 O.sub.2 (345.407). Calculated: C 73.02, H 5.54, N 
12.17. Found: C 72.90, H 5.50, N 11.87. 
EXAMPLE 2 
The production of 4,5-bis(4-chlorophenyl)-2-(2-pyrrolyl)imidazole takes 
place analogously to Example 1 by reacting 4,4'-dichlorobenzil with 
2-formylpyrrole. Melting point 315.degree. C. 
C.sub.19 H.sub.13 Cl.sub.2 N.sub.3 (354.251). Calculated: C 64.42, H 3.70, 
N 11.86, Cl 20.02. Found: C 64.58, H 3.71 ,N 11.42, Cl 20.31. 
EXAMPLE 3 
4,5-Bis(4-fluorophenyl)-2-(2-pyrrolyl)imidazole is prepared analogously to 
Example 1 by reacting 4,4'-difluorobenzil with 2-formylpyrrole. Melting 
point 276.degree. C. 
C.sub.19 H.sub.13 F.sub.2 N.sub.3 (321.33). Calculated: C 71.02, H 4.08, N 
13.08, F 11.82. Found: C 70.79, H 4.12, N 12.93, F 11.45. 
EXAMPLE 4 
4,5-Bis(4-methoxyphenyl)-2-(1-methyl-2-pyrrolyl)-imidazole is produced 
according to Example 1 by reacting 4,4'-dimethoxybenzil with 
1-methyl-2-formylpyrrole. Melting point 110.degree. C. 
C.sub.22 H.sub.21 N.sub.3 O.sub.2 (359.4). Calculated: C 73.52, H 5.89, N 
11.69. Found: C 73.24, H 6.05, N 11.36. 
EXAMPLE 5 
The preparation of 
4,5-bis(4-methoxyphenyl)-2-(3-ethoxycarbonyl-2-pyrrolyl)imidazole takes 
place analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
2-formyl-3-ethoxycarbonylpyrrole. Melting point 193.degree. C. 
C.sub.24 H.sub.23 N.sub.3 O.sub.4 (417.5). Calculated: C 69.02, H 5.55, N 
10.05. Found: C 68.86, H 5.98, N 10.16. 
EXAMPLE 6 
The production of 
4,5-bis(4-methoxyphenyl)-2-(4-methoxycarbonyl-2-pyrrolyl)imidazole is 
conducted in analogy to Example 1 by reacting 4,4'-dimethoxybenzil with 
2-formyl-4-methoxycarbonylpyrrole. Melting point 236.degree. C. 
C.sub.23 H.sub.21 N.sub.3 O.sub.4 (403.4). Calculated: C 68.47, H 5.25, N 
10.42. Found: C 68.51, H 5.18, N 10.12. 
Preparation of Starting Material 
3.6 g (27 millimoles) of 2-cyanopyrrole-4-carboxylic acid methyl ester, 17 
g of Raney nickel, and 450 ml of 75% formic acid are introduced, in a 
flask, into an oil bath preheated to 120.degree. C. and made to react for 
one hour. Subsequently, the mixture is poured into 1 liter of ice water 
and repeatedly extracted with ether. After drying and concentration of the 
ether phase, 1.4 g (36% of theory) of 2-formylpyrrole-4-carboxylic acid 
methyl ester is obtained, mp 126.degree. C. 
EXAMPLE 7 
4,5-Bis(4-methoxyphenyl)-2-(1-benzyl-2-pyrrolyl)-imidazole is produced 
analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
1-benzyl-2-formylpyrrole. Melting point 183.degree. C. 
C.sub.28 H.sub.25 N.sub.3 O.sub.2 (435.5). Calculated: C 77.21, H 5.78, N 
9.64. Found: C 77.03, H 5.93, N 9.01. 
EXAMPLE 8 
The preparation of 
4,5-bis(4-methoxyphenyl)-2-(1-phenylsulfonyl-2-pyrrolyl)imidazole takes 
place analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
1-phenylsulfonyl-2-formylpyrrole. Melting point 135.degree. C. 
C.sub.27 H.sub.23 N.sub.3 O.sub.4 S (485.6). Calculated: C 66.79, H 4.77, N 
8.65 S 6.60. Found: C 66.81, H 4.45, N 8.52, S 6.43. 
EXAMPLE 9 
The production of 4,5-bis(4-methoxyphenyl)-2-(3-pyrrolyl)imidazole is 
conducted analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
3-formylpyrrole. Melting point 232.degree. C. 
C.sub.21 H.sub.19 N.sub.3 O.sub.2 (345.4). Calculated: C 73.02, H 5.54, N 
12.17. Found: C 73.44, H 5.56, N 11.84. 
EXAMPLE 10 
4,5-Bis(4-methoxyphenyl)-2-(2-ethoxycarbonyl)-3-pyrrolyl)imidazole is 
prepared analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
2-ethoxycarbonyl-3-formylpyrrole. Melting point 176.degree. C. 
C.sub.24 H.sub.23 N.sub.3 O.sub.4 (417.4). Calculated: C 69.05, H 5.55, N 
10.07. Found: C 69.26, H 5.45, N 9.85. 
EXAMPLE 11 
2-Ethoxycarbonyl-4-[4,5-bis(4-methoxyphenyl)-2-imidazolyl]-5-methylpyrrole- 
3-acetic acid ethyl ester is prepared in analogy to Example 1 by reacting 
4,4'-dimethoxybenzil with 
2-ethoxycarbonyl-4-formyl-5-methyl-3-pyrrole-acetic acid ethyl ester. 
Melting point 186.degree. C. 
C.sub.29 H.sub.31 N.sub.3 O.sub.6 (517.6). Calculated: C 67.30, H 6.04, N 
8.12. Found: C 67.06, H 6.22, N 7.96. 
EXAMPLE 12 
The production of 
4,5-bis(4-methoxyphenyl)-2-(3,4,5-trimethyl-2-pyrrolyl)imidazole takes 
place as disclosed in Example 1 by reacting 4,4'-dimethoxybenzil with 
3,4,5-trimethyl-2-formylpyrrole. Melting point 115.degree. C. 
C.sub.24 H.sub.25 N.sub.3 O.sub.2 (387.5). Calculated: C 74.39, H 6.50, N 
10.85. Found: C 74.10, H 6.34, N 10.93. 
EXAMPLE 13 
4,5-Bis(4-methoxyphenyl)-2-(3,4-dimethyl-2-pyrrolyl)imidazole is prepared 
analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
3,4-dimethyl-2-formylpyrrole. Melting point 134.degree. C. 
C.sub.23 H.sub.23 N.sub.3 O.sub.2 (373.5). Calculated: C 73.97, H 6.21, N 
11.25. Found: C 73.78, H 6.30, N 11.02. 
EXAMPLE 14 
The preparation of 
2-ethoxycarbonyl-4-[4,5-bis-(4-methoxyphenyl)-2-imidazolyl]-5-methylpyrrol 
e-3-propionic acid ethyl ester is conducted in analogy to Example 1 by 
reacting 4,4'-dimethoxybenzil with 
2-ethoxycarbonyl-4-formyl-5-methylpyrrole-3-propionic acid ethyl ester. 
Melting point 90.degree. C. 
C.sub.30 H.sub.33 N.sub.3 O.sub.6 (531.6). Calculated: C 67.78, H 6.26, N 
7.90. Found: C 67.45, H 6.46, N 7.83. 
EXAMPLE 15 
7-[4,5-Bis(4-methoxyphenyl)-2-imidazolyl]-2,3-dihydro-1H-pyrrolizine is 
produced analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
7-formyl-2,3-dihydro-1H-pyrrolizine. Melting point 238.degree. C. 
C.sub.24 H.sub.23 N.sub.3 O.sub.2 (385.4). Calculated: C 74.78, H 6.01, N 
10.90. Found: C 74.60, H 6.11, N 10.64. 
Preparation of Starting Material 
13.21 g (0.1 mol) of 7-cyano-2,3-dihydro-1H-pyrrolizine is dissolved in 150 
ml of absolute toluene and cooled to -20.degree. C. To this solution is 
added dropwise 108 ml (0.13 mol) of a 1.2-molar diisobutyl aluminum 
hydride solution in toluene; the mixture is then warmed to room 
temperature, stirred for another hour, and decomposed with 300 ml of 10% 
aqueous citric acid solution. The product is extracted with methylene 
chloride, the organic phase is dried, concentrated, and the residue 
recrystallized from ether, thus obtaining 8.0 g (59% of theory) of 
7-formyl-2,3-dihydro-1H-pyrrolizine, mp 58.degree. C. 
EXAMPLE 16 
The production of 4,5-bis(4-methoxyphenyl)-2-(2-indolyl)imidazole takes 
place analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
2-formylindole. Melting point 130.degree. C. 
C.sub.25 H.sub.21 N.sub.3 O.sub.2 (395.5). Calculated: C 75.93, H 5.35, N 
10.63. Found: C 75.61, H 5.50, N 10.38. 
EXAMPLE 17 
4,5-Bis(4-methoxyphenyl)-2-(3-indolyl)imidazole is prepared analogously to 
Example 1 by reacting 4,4'-dimethoxybenzil with 3-formylindole. Melting 
point 246.degree. C. 
C.sub.25 H.sub.21 N.sub.3 O.sub.2 (395.5). Calculated: C 75.93, H 5.35, N 
10.63. Found: C 75.81, H 5.70, N 10.49. 
EXAMPLE 18 
The preparation of 4,5-bis(4-methoxyphenyl)-2-(2-imidazolyl)imidazole takes 
place in analogy to Example 1 by reacting 4,4'-dimethoxybenzil with 
2-formylimidazole. Melting point 178.degree. C. 
C.sub.20 H.sub.18 N.sub.4 O.sub.2 (346.42). Calculated: C 69.35, H 5.24, N 
16.18. Found: C 69.51, H 4.99, N 16.30. 
EXAMPLE 19 
The preparation of 
4,5-bis(4-methoxyphenyl)-2-(1-methyl-2-imidazolyl)imidazole is carried out 
according to Example 1 by reacting 4,4'-dimethoxybenzil with 
1-methyl-2-formylimidazole. Melting point 196.degree. C. C.sub.21 H.sub.20 
N.sub.4 O.sub.2 (360.4). Calculated: C 69.98, H 5.59, N 15.55. Found: C 
69.78, H 5.58, N 15.43. 
EXAMPLE 20 
4,5-Bis(4-methoxyphenyl)-2-(1-benzyl-2-imidazolyl)imidazole is produced 
analogously to Example 1 by reacting 4,4'-dimethoxybenzil with 
1-benzyl-2-formylimidazole. Melting Point 180.degree. C. 
C.sub.27 H.sub.24 N.sub.4 O.sub.2 (436.4). Calculated: C 74.29, H 5.54, N 
12.82. Found: C 73.92, H 5.71, N 12.63. 
EXAMPLE 21 
4,5-Bis(4-methoxyphenyl)-2-(2-thiazolyl)imidazole is prepared analogously 
to Example 1 by reacting 4,4'-dimethoxybenzil with 2-formylthiazole. 
Melting point 199.degree. C. 
C.sub.20 H.sub.17 N.sub.3 O.sub.2 S (363.2). Calculated: C 66.08, H 4.72, N 
11.57, S 8.83.Found: C 66.04, H 5.01, N 11.39, S 8.59. 
EXAMPLE 22 
1.61 g of 4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-imidazole, 6.29 g of 
dibromoethane, and 1.5 g of ethyldiisopropylamine are dissolved in 120 ml 
of acetonitrile and heated to reflux for 48 hours. The reaction solution 
is then evaporated to dryness under vacuum. Separation of the 
4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-1-(2-bromoethyl)imidazole by 
chromatography on silica gel with hexane/ethyl acetate (1:1) yields 0.5 g 
of this compound. Melting point 135.degree. C. 
C.sub.23 H.sub.22 N.sub.3 O.sub.2 Br (452.349). Calculated: C 61.06, H 
4.90, N 9.29, Br 17.68. Found: C 60.95, H 4.85, N 9.32, Br 17.40. 
EXAMPLE 23 
The preparation of 
4,5-bis(4-fluorophenyl)-2-(2-pyrrolyl)-1-(3-bromopropyl)imidazole takes 
place analogously to Example 22 by reacting 
4,5-bis(4-fluorophenyl)-2-(2-pyrrolyl)imidazole with 1,3-dibromopropane. 
Melting point 157.degree. C. 
C.sub.22 H.sub.20 F.sub.2 N.sub.3 Br (442.301). Calculated: C 59.74, H 
4.10, N 9.50, F 8.59, Br 18.07. Found: C 59.60, H 4.22, N 9.39, F 8.44, Br 
18.01. 
EXAMPLE 24 
The preparation of 
4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-1-(4-iodobutyl)imidazole is 
conducted analogously to Example 22 by reacting 
4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)imidazole with 1,4-diiodobutane. 
Melting point 85.degree. C. 
C.sub.25 H.sub.26 N.sub.3 O.sub.2 I (527.407). Calculated: C 56.94, H 4.97, 
N 7.97, I 24.06. Found: C 57.20, H 5.03, N 7.48, I 23.74. 
EXAMPLE 25 
4,5-Bis(4-methoxyphenyl)-2-(2-pyrrolyl)-1-(3-bromopropyl)imidazole is 
prepared analogously to Example 22 by reacting 
4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-imidazole with 1,3-dibromopropane. 
Melting point 97.degree. C. 
C.sub.24 H.sub.24 N.sub.3 O.sub.2 Br (466.4). Calculated: C 61.18, H 5.07, 
N 8.26, Br 15.42. Found: C 61.31, H 5.19, N 8.43, Br 15.70. 
EXAMPLE 26 
The production of 4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-1-butylimidazole 
takes place according to Example 22 by reacting 
4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-imidazole with bromobutane. 
Melting point 76.degree. C. 
C.sub.25 H.sub.27 N.sub.3 O.sub.2 (401.5).Calculated: C 74.79, H 6.78, N 
10.47. Found: C 74.51, H 7.00, N 10.28. 
EXAMPLE 27 
The preparation of 
4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-1-methylimidazole is effected 
analogously to Example 22 by reacting 
4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-imidazole with iodomethane. 
Melting point 134.degree. C. 
C.sub.22 H.sub.21 N.sub.3 O.sub.2 (359.4). Calculated: C 73.52, H 5.89, N 
11.69. Found: C 73.61, H 5.80, N 11.49. 
EXAMPLE 28 
0.760 g of 
4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-1-(2-bromoethyl)imidazole is 
dissolved in 20 ml of dimethylformamide, combined with 0.15 g of sodium 
hydride (55% strength in white oil), and stirred for one hour at 
60.degree. C. The reaction mixture is poured into ice water, extracted 
with ethyl acetate, and separated by chromatography on silica gel, eluent 
ethyl acetate/hexane (2:1). Yield: 0.400 g of 
2,3-bis(4-methoxyphenyl)-5,6-dihydroimidazo[1,2-a]-pyrrolo[2,1-c]pyrazine, 
mp 172.degree. C. 
C.sub.23 H.sub.21 N.sub.3 O.sub.2 (371.437). Calculated: C 74.37, H 5.71, N 
11.31. Found: C 74.07, H 5.90, N 10.85. 
EXAMPLE 29 
1.4 g of 4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-1-(3-bromopropyl)imidazole 
is cyclized analogously to Example 28 to 0.6 g of 
2,3-bis(4-methoxyphenyl)-6,7-dihydro-5H-imidazo[1,2-a]pyrrolo[2,1-c]-1,4-d 
iazepin, mp 140.degree. C. 
EXAMPLE 30 
1.53 g of 4,5-bis(4-methoxyphenyl)-2-(2-pyrrolyl)-1-(4-iodobutyl)imidazole 
is cyclized analogously to Example 28 to 0.85 g of 
2,3-bis(4-methoxyphenyl)-5,6,7,8-tetrahydroimidazo-[1,2-a]pyrrolo[2,1-c]-1 
,4-diazocin, mp 181.degree. C. 
C.sub.25 H.sub.25 N.sub.3 O.sub.2 (399.5). Calculated: C 75.16, H 6.31, N 
10.52. Found: C 75.41, H 6.48, N 10.34. 
The preceding examples can be repeated with similar success by substituting 
the generically or specifically described reactants and/or operating 
conditions of this invention for those used in the preceding examples. 
From the foregoing description, one skilled in the art can easily 
ascertain the essential characteristics of this invention, and without 
departing from the spirit and scope thereof, can make various changes and 
modifications of the invention to adapt it to various usages and 
conditions.