Patent Publication Number: US-4225724-A

Title: 1-(2-Phenylureylene)imidazoles

Description:
This is a division of Application Ser. No. 858,515, filed Dec. 8, 1977, which application issued July 3, 1979 as U.S. Pat. No. 4,160,097 and, which is a continuation-in-part of Application Ser. No. 757,640, filed Jan. 7, 1977 and now abandoned. 
    
    
     This invention relates to certain 4-substituted imidazo-[1,2-a]quinoxalines and to processes for preparing the same. It also concerns certain 1-(2-acylaminophenyl)imidazoles which among other things are useful as intermediates in the preparation of 4-substituted imidazo[1,2-a]quinoxalines. The aforesaid compounds are useful for a variety of purposes which will be described in more detail below. Some of these are useful as immunosuppressants; whereas, others are useful as anti-inflammatory agents or display antifungal activity. Moreover, some exhibit two or all three of these activities. 
     The 4-substituted imidazo[1,2-a]quinoxalines encompassed in the present invention may be described by the formula: ##STR2## and pharmaceutically acceptable salts thereof wherein X is --R 1  or --NHR 2  wherein: 
     (1) R 1  is bonded to a ring carbon by a carbon-to-carbon linkage and is an aliphatic, cycloaliphatic, substituted phenyl, fused bicyclic aryl; or monocyclic aryl-substituted aliphatic; and 
     (2) R 2  is a radical bonded to a nitrogen by a carbon to nitrogen linkage; said radical being selected from the group consisting of aliphatic, cycloaliphatic, phenyl, substituted phenyl, fused bicyclic aryl or a monocyclic aryl-substituted aliphatic group. 
     When R 1  is an aliphatic group, it may be a straight chain or branched chain hydrocarbon group which is saturated, monounsaturated or polyunsaturated. It may also comprise a straight chain or branched chain group containing other than carbon-to-carbon bondings e.g. ether linkages, carbon to halogen linkages, etc. Ordinarily, it will contain from about 1 to 18 carbon atoms, the most typical radicals of this group being the alkyl radicals having from 1 to 18 carbon atoms. 
     By way of illustrating the aliphatic groups that may be represented by R 1 , the following are given: CH 3  --; CH 3  CH 2  --; CH 3  CH 2  --CH 2  --; CH 3  (CH 2 ) n  -- in which n is 3, 4, 5, 6, 7, 8, 14 and 16 respectively; (CH 3 ) 2  CH--CH 2  --; CH 3  (CH 2 ) 3  (CH 3  CH 2 )CH--, CH 2  ═CH--(CH 2 ) 8  --, alkoxyalkyl in which the alkyl moieties have from 1 to 4 carbon atoms e.g. methoxymethyl; halogenoalkyl (i.e. CH 2  Cl--; CH 3  CHCl--; CHCl 2  --; CCl 3  --; CH 2  Br--; CF 3 ). 
     When R 1  is a cycloaliphatic radical it will most often be a cycloalkyl radical containing 3 to 8 carbon atoms or a cycloalkenyl radical containing 5 to 6 carbon atoms. By way of illustrating the cycloaliphatic radicals that may correspond to R 1  in formula I mention may be made of the ##STR3## 
     When R 1  is a substituted phenyl radical in formula I above, the phenyl group may have from 1 to 5 substituents but will usually be mono, di or trisubstituted. Typical among the groups that may be contained in the phenyl group are (a) alkyl groups which are branched or straight chain containing 1 to 6 carbon atoms e.g. methyl, ethyl, tertiary butyl; (b) alkoxyl groups containing 1 to 6 carbon atoms e.g. methoxy, ethoxy; (c) hydroxy; (d) acyloxy containing 1 to 18 carbon atoms; (e) halogen e.g. 1 or 2 Cl, F, Br, I preferably in the meta and/or para position; (f) nitro; (g) amino; (h) acylamino in which the acylamino moiety is derived from an alkanoic acid containing 1 to 18 carbon atoms and benzamides in which the benzene ring is unsubstituted or monosubstituted, disubstituted or trisubstituted with alkyl groups containing 1 to 5 carbon atoms or halogen atoms; (i) polyhydroxyalkylamino groups containing 4 to 8 carbon atoms; (j) cyano; (k) trifluoromethyl; (l) mercapto; (m) alkylthio; (n) acylthio containing 1 to 18 carbon atoms; (o) carboxyl; (p) carboalkoxyl containing 1 to 8 aliphatic carbon atoms; (q) phenyl; (r) phenoxy, and combinations thereof. 
     When R 1  is a fused bicyclic aryl radical, it may be a substituted or unsubstituted radical. These are exemplified by such fused bicyclic hydrocarbon radicals as 1-naphthyl, 2-naphthyl etc. 
     When R 1  is a monocyclic aryl substituted aliphatic radical, the monocyclic aryl moiety may be either of the substituted or unsubstituted variety. The aliphatic moiety of this group may be either of the saturated or unsaturated straight chain or branched chain hydrocarbon variety or it may contain other than carbon-to-carbon bonding. This may be illustrated by such groups as phenoxymethyl; benzyl, styryl, ##STR4## 
     The group R 2  in the radical --NHR 2  of formula I above is exemplified by the same radicals given above in illustrating the radical --R 1 . In addition, R 2  may also be phenyl as in the case of the group ##STR5## 
     In general, the compounds included in formula I above as well as the cases in formula I in which X is hydrogen or phenyl may be prepared by heating the corresponding 1-(2-acylaminophenyl)imidazole at reflux in the presence of cyclizing quantities of a cyclizing agent e.g. polyphosphoric acid or phosphorous oxychloride, etc. for sufficient time to cause significant cyclization of this reactant. More particularly, the 1-(2-acylaminophenyl)imidazole reactants that can be employed in this process may be described by the general formula: ##STR6## in which X 2  is R 5  or --NHR 2  wherein: R 5  is hydrogen or an aliphatic, cycloaliphatic, phenyl or substituted phenyl, fused bicyclic aryl or monocyclic aryl substituted aliphatic radical and 
     R 2  has the same values assigned to it in connection with formula I above. 
     The group R 5  in formula II is illustrated by the same groups that illustrate R 1  in formula I. However, in addition, R 5  may also be illustrated by the phenyl radical. 
     The reaction can be depicted by the following equation: ##STR7## 
     The process of equation III is preferably carried out in the presence of an excess of an organic amine solvent. A variety of solvents may be used for this purpose among which mention may be made of the following: pyridine, 2,6-dimethylpyridine, N,N-dimethylaniline, trimethylamine, and N-methylmorpholine, etc. However, the preferred organic solvent is pyridine. 
     The quantity of phosphorous oxychloride that is employed in the reaction can vary somewhat. Generally, however, the phosphorous oxychloride will be employed in the range of from about one-half mole to about 6 moles and preferably one-half mole to two moles per mole of compound II. 
     The desired product IV may be recovered from the reaction mixture using any of the ordinary techniques well known to those skilled in this art. The time of reaction will vary depending upon, among other things, the particular reactants or molar quantities of reactants employed. In general, the reaction time will be from about 30 to 120 minutes. 
     The temperature employed in carrying out the reaction will also vary depending upon the particular reactants selected, the solvent and other factors. Ordinarily, the temperature employed will be the reflux temperature of the reaction mixture. This generally will be in the range of from about 95° C. to 195° C. 
     The method of preparing the 1-(2-acylaminophenyl)imidazoles (compound II) will vary depending on the particular type that is being made. Thus, for example, in preparing compound of the general type: ##STR8## where R 5  is hydrogen, aliphatic, cycloaliphatic, phenyl, substituted phenyl, fused bicyclic aryl or monocyclic aryl substituted aliphatic group, the 1-(2-acylaminophenyl)imidazole is reacted with the appropriate acid halide e.g. the acid chloride. 
     This can be expressed by the following equation: ##STR9## in which R 5  has the value ascribed to it above. The reaction will usually be carried out employing equimolar amounts of the appropriate acid chloride and in the presence of excess solvent (e.g. pyridine) at reflux. 
     When the compounds in question are of the phenylureylene type e.g. ##STR10## wherein R 2  is hydrogen, aliphatic, cycloaliphatic, phenyl, substituted phenyl, fused bicyclic aryl or monocyclic aryl substituted aliphatic group, these are prepared by reacting the aminophenylimidazole with the appropriate isocyanate. This can be expressed by the following equation: ##STR11## in which R 2  has the value ascribed to it above. This reaction is preferably carried out in the presence of a solvent and at steam bath temperatures. A typical solvent that can be employed is toluene and the reactants are usually used in about equimolar quantities. The products obtained from reactions VI and VIII may be recovered using standard techniques well known to those skilled in this art. 
     PRIOR ART 
     U.S. Pat. No. 3,887,566 discloses imidazo[1,2-a]quinoxaline and 4-phenylimidazo[1,2-a]quinoxaline. However, this reference does not disclose the 4-substituted imidazo[1,2-a]quinoxalines of the present invention nor the process for making these compounds. The activity disclosed in this reference for these compounds is as cardiovascular drugs. There is no disclosure of the fact that these compounds may have immunosuppressant activity, antifungal activity or non-steroidal anti-inflammatory action. It is in fact interesting to note that the unsubstituted imidazo[1,2-a]quinoxaline lacks immunosuppressant activity while the 4-phenylimidazo[1,2-a]quinoxaline has only minor activity which is greatly increased by substitution on the para- and meta-positions on the benzene ring. 
     Uryukina et al, Khim. Geterotsikl. Soedin., 1972, 1558-60 (See C.A. 78, 58345 t  (1973) discloses the unsubstituted and the 7-methyl, methoxy, and bromo substituted imidazo[1,2-a]quinoxalines. No 4-substituted products are disclosed nor is any utility disclosed for these compounds. 
     Kovalev et al, Farmakol. Toksikol (Moscow), 36 (2), 232-238, 1973 (See C.A. 78 154693 a ) also discloses the 7-methoxyimidazo[1,2-a]quinoxaline and suggests the use of this material as an hypotensive agent. This reference likewise does not disclose the 4-substituted imidazo[1,2-a]quinoxalines of the present invention or their utility. 
     Japanese Pat. Nos. 10677/74 and 10678/74 disclose certain 4-substituted 1,2-dihydroimidazo[1,2-a]quinoxalines and the fact that these materials are useful as anti-inflammatory agents. These references do not show the unhydrogenated compounds of this invention. Moreover, no immunosuppressant activity or antifungal activity is disclosed. 
     Siminov et al, Khim. Geterotsikl, Soedin, 7, 570 (1971) (See C.A. 76, 25242 n  1972) discloses a process for synthesizing imidazo[1,2-a]quinoxaline involving the reduction of 1-(o-nitrophenyl)-2-formylimidazole. This is obviously not related to the process of the present invention. 
     The following Examples are given to further illustrate the present invention. It is to be understood, however, that they are not limitative of this invention. 
     The compounds described in the Tables below were prepared as described. Melting points were obtained by the capillary tube method using a Mel-Temp melting point apparatus and are uncorrected. Ultraviolet spectra were obtained in ethanol solution using a Beckman U.V. Acta III or a Beckman DBG. 1-(2-aminophenyl)imidazole was prepared as reported by A. F. Pozharskii, A. M. Siminov and L. M. Sitkina, Khim. Geterotskl. Soedin. 5, 1916 (1969) [Chem. Abstr., 72 11427 a  (1970)]. 
     Table I below further illustrates the preparation of the aliphatic, cycloaliphatic and monocyclic aryl substituted aliphatic-amidophenylimidazoles of the present invention. Table II further exemplifies the preparation of the aryl (including the fused ring aryl) amidophenylimidazoles of this invention. 
     Except as noted in Tables I and II, the amides were prepared by reacting equimolar amounts of the appropriate acid chloride with 1-(2-aminophenyl)imidazole in the presence of excess pyridine on a steam bath for 45 minutes. The reaction mixture was then stirred into ice water and the crude product isolated according to one of the following methods. 
     Method A. If a solid was obtained, it was directly crystallized from the solvent indicated in Table I. 
     Method B. If an oil was obtained, it was dissolved in a minimum amount of chloroform and passed through an alumina column with the amount of alumina being approximately twenty times the weight of the crude solid; elution was with chloroform. The chloroform was evaporated from the crude product which was crystallized as indicated in Table I. 
     Method C. If a solution was obtained in the ice water mixture, the pyridine/water azeotrope was removed until the crude product separated. It was then treated as in Method B above. 
     
                                           TABLE I                                 
__________________________________________________________________________
 ##STR12##                                                                
1-(2-alkanamidophenyl)imidazoles                                          
                       Isolation                                          
                            %   Crystallization                           
                                              Analysis                    
No.                                                                       
   R                   Mehtod                                             
                            Yield                                         
                                Solvent  m.p., °C.                 
                                              Calc&#39;d                      
                                                   Found                  
__________________________________________________________________________
 1 H.sup.a             C    63.3                                          
                                Water    200-204                          
                                              C,64.16                     
                                                   64.26                  
                                              H, 4.85                     
                                                    4.71                  
                                              N,22.45                     
                                                   22.30                  
 2 CH.sub.3            A    56.2                                          
                                Ethanol  163-166                          
                                              C,65.66                     
                                                   65.69                  
                                              H, 5.51                     
                                                    5.52                  
                                              N,20.88                     
                                                   20.84                  
 3 CH.sub.3 CH.sub.2.sup.b                                                
                       C    73.9                                          
                                Water    144-146                          
                                              C,66.96                     
                                                   67.26                  
                                              H, 6.09                     
                                                     6.15                 
                                              N,19.52                     
                                                   19.40                  
 4 CH.sub.3 (CH.sub.2).sub.2                                              
                       B    31.1                                          
                                Toluene  108-110                          
                                              C,68.10                     
                                                   67.95                  
                                              H, 6.59                     
                                                    6.52                  
                                              N,18.33                     
                                                   18.25                  
 5 CH.sub.3 (CH.sub.2).sub.3                                              
                       B    49.6                                          
                                Toluene- 123-125                          
                                              C,69.11                     
                                                   69.14                  
                                hexane        H, 7.04                     
                                                    7.00                  
                                              N,17.27                     
                                                   17.17                  
 6 CH.sub.3 (CH.sub.2).sub.4                                              
                       B    49.4                                          
                                isopropyl ether-                          
                                         103-105                          
                                              C,70.01                     
                                                   70.31                  
                                trichloroethylene                         
                                              H, 7.44                     
                                                    7.45                  
                                              N,16.33                     
                                                   16.26                  
 7 CH.sub.3 (CH.sub.2).sub.5                                              
                       A    55.3                                          
                                isopropyl ether                           
                                         96-98                            
                                              C,70.82                     
                                                   70.79                  
                                              H, 7.80                     
                                                    7.74                  
                                              N,15.48                     
                                                   15.23                  
 8 CH.sub.3 (CH.sub.2).sub.6                                              
                       A    55.1                                          
                                isopropyl ether                           
                                         101-102                          
                                              C,71.55                     
                                                   71.67                  
                                              H, 8.12                     
                                                    8.05                  
                                              N,14.72                     
                                                   14.65                  
 9 CH.sub.3 (CH.sub.2).sub.7                                              
                       A    45.6                                          
                                isopropyl ether                           
                                         93-95                            
                                              C,72.21                     
                                                   72.24                  
                                              H, 8.42                     
                                                    8.41                  
                                              N,14.03                     
                                                   13.92                  
10 CH.sub.3 (CH.sub.2).sub.8                                              
                       A    60.6                                          
                                isopropyl                                 
                                         79-81                            
                                              C,72.81                     
                                                   73.38                  
                                ether-hexane  H, 8.68                     
                                                    8.85                  
                                              N,13.41                     
                                                   13.02                  
11 CH.sub.3 (CH.sub.2).sub.14                                             
                       B    58.1                                          
                                isopropyl ether                           
                                         94-96                            
                                              C,75.52                     
                                                   75.12                  
                                              H, 9.89                     
                                                    9.76                  
                                              N,10.57                     
                                                   10.38                  
12 CH.sub.3 (CH.sub.2).sub.16                                             
                       B    80.6                                          
                                isopropyl ether                           
                                         98-100                           
                                              C,76.19                     
                                                   76.57                  
                                              H,10.18                     
                                                   10.28                  
                                              N, 9.87                     
                                                    9.79                  
13 (CH.sub.3).sub.3 C.sup.b                                               
                       C    48.8                                          
                                benzene  102-104                          
                                              C,69.11                     
                                                   69.15                  
                                              H, 7.04                     
                                                    7.26                  
                                              N,17.27                     
                                                   17.19                  
14 (CH.sub.3).sub.2 CHCH.sub.2                                            
                       C    25.4                                          
                                benzene  128-130                          
                                              C,69.40                     
                                                   69.60                  
                                              H, 6.66                     
                                                    7.00                  
                                              N,17.34                     
                                                   17.40                  
15 CH.sub.3 (CH.sub.2).sub.3 (CH.sub.3 CH.sub.2)CH                        
                       B    32.8                                          
                                benzene  125-127                          
                                              C,71.55                     
                                                   71.86                  
                                              H, 8.12                     
                                                    7.84                  
                                              N,14.72                     
                                                   14.95                  
16 CH.sub.2CH(CH.sub.2).sub.8                                             
                       A    76.8                                          
                                isopropyl                                 
                                         92-94                            
                                              C,73.81                     
                                                   74.26                  
                                ether-hexane  H, 8.36                     
                                                    8.50                  
                                              N,12.91                     
                                                   12.30                  
17 CH.sub.3 (CH.sub.2).sub.3 (CH.sub.2CHCH).sub.2 (CH.sub.2).sub.7        
                       C    3.6 C        73.76                            
                                              C,76.92                     
                                                   76.73                  
                                              H, 9.32                     
                                                    9.36                  
                                              N, 9.97                     
                                                    9.78                  
18                                                                        
    ##STR13##          C    41.9                                          
                                ethanol  145.147                          
                                              C,73.63 H,                  
                                                   73.81  5.57 15.41      
19                                                                        
    ##STR14##          C    7.7 diethyl ether                             
                                         205-207                          
                                              C,74.73 H,                  
                                                   74.83  6.32 13.59      
20                                                                        
    ##STR15##          A    43.0                                          
                                ethanol  161-164                          
                                              C,74.72 H,                  
                                                   74.94  5.47 14.55      
21 CH.sub.3 OCH.sub.2  A    49.8                                          
                                Toluene  146-147                          
                                              C,62.33                     
                                                   61.99                  
                                              H, 5.66                     
                                                    5.74                  
                                              N,18.17                     
                                                   18.48                  
22                                                                        
    ##STR16##          A    77.7                                          
                                Toluene  136.5- 138.5                     
                                              C,69.61 H,                  
                                                   69.82  5.37 14.04      
23                                                                        
    ##STR17##          A    10.1                                          
                                isopropanol                               
                                         207-209                          
                                              C,68.71 H,                  
                                                   68.67  5.85 18.67      
24                                                                        
    ##STR18##          A    55.6                                          
                                Toluene  151-153                          
                                              C,69.69 H,                  
                                                   69.44  6.21 17.55      
25                                                                        
    ##STR19##          A    67.3                                          
                                Toluene  142.5- 145                       
                                              C,71.35 H,                  
                                                   70.88  6.92 15.59      
26                                                                        
    ##STR20##          A    21.6                                          
                                ethanol  196- 198.5                       
                                              C,72.16 H,                  
                                                   71.87  6.33 15.40      
27 CH.sub.2 Cl         B    11.9                                          
                                water    255(dec.)                        
                                              C,56.06                     
                                                   55.92                  
                                              H, 4.28                     
                                                    4.26                  
                                              N,17.83                     
                                                   17.72                  
28 CH.sub. 3 CHCl      A    27.9                                          
                                Toluene  143.5-                           
                                              C,57.72                     
                                                   57.54                  
                                         145.5                            
                                              H, 4.85                     
                                                    4.92                  
                                              N,16.83                     
                                                   17.16                  
29 CHCl.sub.2.sup.b    A    33.2                                          
                                benzene  162-165                          
                                              C,48.91                     
                                                   48.94                  
                                              H, 3.36                     
                                                    3.24                  
                                              N,15.56                     
                                                   15.42                  
                                              Cl,26.25                    
                                                   26.17                  
30 CF.sub.3            A    22.0                                          
                                ethanol  165-167                          
                                              C,51.77                     
                                                   51.58                  
                                              H, 3.16                     
                                                    3.20                  
                                              N,16.47                     
                                                   16.53                  
32                                                                        
    ##STR21##          C    14.1                                          
                                trichloro- ethylene                       
                                         128-130                          
                                              C,60.23 H,                  
                                                   60.21  5.10 16.16      
__________________________________________________________________________
 Notes:                                                                   
 .sup.a Prepared from aceticformic anhydride according to R. J. Jones, J. 
 Am. Chem. Soc., 71,644(1949). After removal by distillation of excess    
 solvent, residue dissolved in water and neutralized with NaOH to provide 
 crude product.                                                           
 .sup.b Prepared via the anhydride.                                       
 .sup.c Could not be crystallized; purified by chromatography on alumina  
 with ethyl acetate as elutant.                                           
 
    
     
                                           TABLE II                                
__________________________________________________________________________
 ##STR22##                                                                
1-(2-Arylamidophenyl) imidazoles                                          
                Isolation                                                 
                     %   Crystallization        Analysis                  
No.                                                                       
     Ar         Method                                                    
                     Yield                                                
                         Solvent   m.p., °C.                       
                                         λmax. (Am)                
                                                Calc&#39;d                    
                                                     Found                
__________________________________________________________________________
34                                                                        
    ##STR23##   A    44.9                                                 
                         dimethoxyethane                                  
                                   148-150                                
                                         225(21,720)                      
                                                C,72.99 H, 4.98 N,15.96   
                                                     73.30  5.08 16.04    
35                                                                        
    ##STR24##   A    58.7                                                 
                         ethanol   190-192.5                              
                                         262(21,400)                      
                                                C,73.63 H, 5.45 N,15.15   
                                                     73.10  5.32 15.46    
36                                                                        
    ##STR25##   B    58.3                                                 
                         benzene   147- 148.5                             
                                         231,sh(18,200)                   
                                                C,73.63 H, 5.45 N,15.15   
                                                     73.63  5.24 15.36    
37                                                                        
    ##STR26##   B    57.4                                                 
                         benzene   143-146.5                              
                                         236(23,400)                      
                                                C,73.63 H, 5.45 N,15.15   
                                                     73.28  5.29 15.27    
38                                                                        
    ##STR27##   A    53.0                                                 
                         benzene   151-153                                
                                         c.     C,61.63                   
                                                     60.97  3.62 12.34    
39                                                                        
    ##STR28##   B    79.3                                                 
                         ethyl acetate                                    
                                   136-138                                
                                         239(20,400)                      
                                                C,75.21 H, 6.63 N,13.27   
                                                     75.06  6.45 13.31    
40                                                                        
    ##STR29##   A    45.5                                                 
                         isopropanol                                      
                                   198-200                                
                                         276(28,100)                      
                                                C,77.86 H, 5.05 N,12.38   
                                                     77.46  4.76 12.09    
41                                                                        
    ##STR30##   A    73.5                                                 
                         dimethylformamide, ethanol                       
                                   194-196                                
                                         260(17,810)                      
                                                C,62.33 H,                
                                                     62.26  3.69 18.10    
42                                                                        
    ##STR31##   A    74.4                                                 
                         dimethylformamide, water                         
                                   198-202.5                              
                                         250(16,500)                      
                                                C,62.33 H,                
                                                     62.27  4.00 18.37    
43                                                                        
    ##STR32##   A    87.41                                                
                         dimethylformamide, water                         
                                   254-256                                
                                         c.     C,54.40 H,                
                                                     54.35  3.31 19.82    
44                                                                        
    ##STR33##   A    60.87                                                
                         dimethylformamide, water                         
                                   219-220.5                              
                                         234(1,500)                       
                                                C,70.82 H,                
                                                     70.14  4.45 19.15    
45                                                                        
    ##STR34##   B    56.8                                                 
                         benzene   205-208                                
                                         229(18,500)                      
                                                C,68.32 H,                
                                                     67.86  4.02 15.17    
46                                                                        
    ##STR35##   A    53.2.sup.a                                           
                         dimethylformamide, water                         
                                   93-96 260(10,100)                      
                                                C,66.20 H,                
                                                     65.96  4.37 14.40    
47                                                                        
    ##STR36##   A    b.  dimethylformamide                                
                                   189-190.5                              
                                         240(22,100)                      
                                                C,56.16 H,                
                                                     56.03  3.58 12.51    
48                                                                        
    ##STR37##   A    40.1                                                 
                         dimethylformamide, water                         
                                   199-201.5                              
                                         258(20,100)                      
                                                C,56.16  H,               
                                                     55.84  3.58 12.48    
49                                                                        
    ##STR38##   A    38.7                                                 
                         dimethylformamide, ethanol                       
                                   201-203                                
                                         261(16,700)                      
                                                C,64.54 H,                
                                                     64.70  4.05 13.95    
50                                                                        
    ##STR39##   B    68.5                                                 
                         ethanol   144-146                                
                                         c.     C,64.54 H,                
                                                     64.82  3.92 14.59    
51                                                                        
    ##STR40##   A    59.7                                                 
                         ethanol   167-170                                
                                         240(26,410)                      
                                                C,64.54 H,                
                                                     64.41  3.94 13.92    
52                                                                        
    ##STR41##   A    26.6                                                 
                         dimethylformamide, water                         
                                   210-212                                
                                         265(21,000)                      
                                                C,57.85 H,                
                                                     58.05  3.46 13.08    
53                                                                        
    ##STR42##   A    61.2                                                 
                         dimethylformamide, water                         
                                   180.5-183                              
                                         235(22,100)                      
                                                C,57.85 H,                
                                                     57.65  3.51 12.93    
54                                                                        
    ##STR43##   A    42.9                                                 
                         ethanol   186.5-189                              
                                         255(28,480)                      
                                                C,49.38 H, 3.11 N,10.80   
                                                I,32.61                   
                                                     49.22  3.15  10.85   
                                                     32.89                
55                                                                        
    ##STR44##   B    58.6                                                 
                         isopropanol                                      
                                   146-151                                
                                         263(20,400)                      
                                                C,69.61 H,                
                                                     69.01  5.14 14.36    
56                                                                        
    ##STR45##   B    83.2                                                 
                         dimethylformamide, water                         
                                   171-173                                
                                         281(5,100)                       
                                                C,69.61 H,                
                                                     69.27  5.02 14.28    
57                                                                        
    ##STR46##   B    61.2                                                 
                         benzene   130-132.5                              
                                         244,sh(12,300)                   
                                                C,66.86 H,                
                                                     66.97  5.08 13.54    
58                                                                        
    ##STR47##   C    29.79                                                
                         dimethylformamide, water                         
                                   133.5-136.5                            
                                         281(15,410)                      
                                                C,69.61 H,                
                                                     69.10  5.08 14.18    
59                                                                        
    ##STR48##   B    18.26                                                
                         dimethylformamide, water                         
                                   164.5-166.5                            
                                         c.     C,56.16 H,                
                                                     55.65  3.51 12.37    
60                                                                        
    ##STR49##   A    51.07                                                
                         isopropanol                                      
                                   142.5-145.5                            
                                         223(14,420)                      
                                                C,68.32 H,                
                                                     67.79  4.36 14.58    
61                                                                        
    ##STR50##   B    15.68                                                
                         isopropanol-  ethanol                            
                                   203.5-205                              
                                         258(18,840)                      
                                                C,54.40 H,                
                                                     53.78  2.38 12.16    
62                                                                        
    ##STR51##   A    46.9                                                 
                         isopropanol                                      
                                   165.5-167.5                            
                                         237(53,900)                      
                                                C,76.66 H,                
                                                     76.29  4.84 13.27    
63                                                                        
    ##STR52##   A    36.78                                                
                         isopropanol- dimethylformamide                   
                                   175-177                                
                                         289(6,940)                       
                                                C,76.66 H,                
                                                     76.68  4.75 12.01    
190                                                                       
    ##STR53##   B    38.80                                                
                         benzene   156-157.5                              
                                         268(13,800)                      
                                                C,64.58 H,                
                                                     64.58  5.39 12.02    
217                                                                       
    ##STR54##   A    45.8                                                 
                         ethanol   134-136.5                              
                                         273(14,900)                      
                                                C,66.86 H,                
                                                     66.88  5.37 12.68    
__________________________________________________________________________
 Notes:                                                                   
 a. isolated as hemihydrate.                                              
 b. partial loss prevented yield determination.                           
 c. Compound absorbed too low for significant U.V.                        
 
    
     Alkyl-2-(1-imidazolyl)phenylureylenes (Table III) were prepared by the reaction of equimolar amounts of the aminophenylimidazole and the appropriate isocyanate in toluene solution at steam bath temperatures during two or three hours. Upon cooling, the crude product was collected by filtration and treated by one of the following methods: (A) direct crystallization from the appropriate solvent or (B) dissolved in hot dimethylformamide and precipitated with water followed by crystallization. 
     
                                           TABLE III                               
__________________________________________________________________________
 ##STR55##                                                                
Alkyl-2-(1-imidazolyl)phenylureylenes                                     
             Isolation                                                    
                  90  Crystallization      Analysis                       
No.                                                                       
   R         Method                                                       
                  Yield                                                   
                      Solvent   m.p., °C.                          
                                     λmax.(Am)                     
                                           Calc&#39;d                         
                                                Found                     
__________________________________________________________________________
64 CH.sub.3  A    41.6                                                    
                      ethanol   194-196                                   
                                     240(15,500)                          
                                           C,61.60                        
                                                61.22                     
                                           H, 5.59                        
                                                 5.48                     
                                           N,25.91                        
                                                26.11                     
65 CH.sub.3 CH.sub.2                                                      
             B    27.3                                                    
                      trichloroethylene                                   
                                173-175                                   
                                     278(1,200)                           
                                           C,62.59                        
                                                62.21                     
                                     242(12,700)                          
                                           H, 6.13                        
                                                 6.04                     
                                           N,24.33                        
                                                24.32                     
66 CH.sub.3 CH.sub.2 CH.sub.2                                             
             B    49.3                                                    
                      trichloroethylene                                   
                                139-141                                   
                                     279(1,200)                           
                                           C,63.92                        
                                                63.75                     
                                     240(12,800)                          
                                           H, 6.60                        
                                                 6.56                     
                                           N,22.93                        
                                                23.00                     
67 CH.sub.3 CH.sub.2 CH.sub.2 CH.sub.2                                    
             B    35.6                                                    
                      isopropanol                                         
                                115-116.5                                 
                                     278(1,400)                           
                                           C,65.09                        
                                                64.84                     
                                     241(15,000)                          
                                           H, 7.02                        
                                                 7.00                     
                                           N,21.69                        
                                                21.78                     
68                                                                        
    ##STR56##                                                             
             A    50.64                                                   
                      dimethylformamide, water                            
                                164-166                                   
                                     241(12,200)                          
                                           C,67.58 H, 7.09 N,19.70        
                                                67.60  7.08 19.44         
__________________________________________________________________________
 
    
     Aryl-2-(1-imidazolyl)phenylureylenes (Table IV) were prepared by reacting equimolar amounts of the aminophenylimidazole and the appropriate arylisocyanate in dry toluene during three hours at steam bath temperatures. The reaction mixture was cooled and the crude product was separated by filtration, and washed with ether and crystallized from the indicated solvent. 
     
                                           TABLE IV                                
__________________________________________________________________________
 ##STR57##                                                                
Aryl-2-(1-imidazolyl) phenylureylenes                                     
                            Recrystallization         Analysis            
No.                                                                       
   Ar                  % Yield                                            
                            Solvent     m.p. °C.                   
                                                λmax.(Am)          
                                                      Calc&#39;d              
                                                           Found          
__________________________________________________________________________
69                                                                        
    ##STR58##          64.6 ethanol     201-203 256(27,640)               
                                                      C,69.05 H, 5.07     
                                                      N,20.13             
                                                           69.13  5.15    
                                                           20.16          
70                                                                        
    ##STR59##          76.9 dimethylformamide- water                      
                                        203.5-207.5                       
                                                258(23,400)               
                                                      C,69.84 H, 5.52     
                                                      N,19.17             
                                                           69.85  5.47    
                                                           19.78          
71                                                                        
    ##STR60##          76.9 ethanol     182-183.5                         
                                                256(25,800)               
                                                      C,69.84 H, 5.52     
                                                      N,19.17             
                                                           69.97  5.35    
                                                           19.12          
72                                                                        
    ##STR61##          78.8 dimethylformamide- water                      
                                        202.5-203.5                       
                                                251(25,500)               
                                                      C,64.86 H, 4.42     
                                                      N,18.91             
                                                           64.77  4.47    
                                                           19.16          
73                                                                        
    ##STR62##          61.9 dimethylformamide- water                      
                                        201-202 253(26,000)               
                                                      C,64.86 H, 4.42     
                                                      N,18.97             
                                                           64.47  4.40    
                                                           19.24          
74                                                                        
    ##STR63##          65.8 dimethylformamide- water                      
                                        220-222 251(23,100)               
                                                      C,64.86 H, 4.42     
                                                      N,18.97             
                                                           64.56  4.41    
                                                           19.14          
75                                                                        
    ##STR64##          76.7 dimethylformamide- water                      
                                        204-206 258(30,900)               
                                                      C,61.45 H, 4.19     
                                                      N,17.91             
                                                           61.57  4.12    
                                                           18.26          
76                                                                        
    ##STR65##          58.1 dimethylformamide- water                      
                                        244-245.5                         
                                                260(32,900)               
                                                      C,55.35 H, 3.48     
                                                      N,16.14             
                                                           54.93  3.47    
                                                           16.25          
77                                                                        
    ##STR66##          70.0 dimethylformamide- water                      
                                        180.5-182.5                       
                                                252(23,000)               
                                                      C,53.80 H, 3.76     
                                                      N,15.68             
                                                           53.88  3.78    
                                                           15.66          
78                                                                        
    ##STR67##          75.2 dimethylformamide- water                      
                                        218-219.5                         
                                                258(28,600)               
                                                      C,53.80 H, 3.67     
                                                      N,15.68             
                                                           53.71  3.66    
                                                           15.35          
79                                                                        
    ##STR68##          53.1 methanol    227-230.5                         
                                                260(27,700)               
                                                      C,53.80 H, 3.67     
                                                      N,15.68             
                                                           52.08  3.56    
                                                           15.12          
80                                                                        
    ##STR69##          83.2 dimethylformamide- water                      
                                        201-202 253(26,000)               
                                                      C,64.86 H, 4.42     
                                                      N,18.97             
                                                           64.47  4.40    
                                                           19.24          
81                                                                        
    ##STR70##          57.79                                              
                            dimethylformamide- water                      
                                        167-170 250(20,710)               
                                                      C,69.84 H, 5.52     
                                                      N,19.17             
                                                           70.10  5.57    
                                                           18.60          
82                                                                        
    ##STR71##          77.4 dimethylformamide- water                      
                                        216.5-218.5                       
                                                256(31,010)               
                                                      C,58.96 H, 3.78     
                                                      N,16.18             
                                                           58.86  3.81    
                                                           15.79          
83                                                                        
    ##STR72##          78.9 dimethylformamide- water                      
                                        212-215 260(27,500)               
                                                      C,70.57 H, 5.92     
                                                      N,18.29             
                                                           70.30  5.83    
                                                           18.00          
84                                                                        
    ##STR73##          76.6 dimethylformamide- water                      
                                        185-188 258(29,590)               
                                                      C,70.57 H, 5.92     
                                                      N,18.29             
                                                           70.30  5.96    
                                                           18.00          
85                                                                        
    ##STR74##          76.2 dimethylformamide- water                      
                                        163.5-166                         
                                                258(28,770)               
                                                      C,70.57 H, 5.92     
                                                      N,18.29             
                                                           70.52  5.81    
                                                           17.94          
86                                                                        
    ##STR75##          67.8 dimethylformamide- water                      
                                        169-172 257(29,920)               
                                                      C,71.83 H, 6.63     
                                                      N,16.75             
                                                           71.61  6.56    
                                                           16.24          
87                                                                        
    ##STR76##          80.6 dimethylformamide- water                      
                                        206-209 282(27,620)               
                                                      C,71.23 H, 6.29     
                                                      N,17.49             
                                                           71.12  6.12    
                                                           17.24          
88                                                                        
    ##STR77##          69.0 dimethylformamide- water                      
                                        204.5-206                         
                                                285(10,630)               
                                                      C,66.22 H, 5.23     
                                                      N,18.17             
                                                           65.96  5.15    
                                                           18.15          
89                                                                        
    ##STR78##          84.0 dimethylformamide- water                      
                                        188     252(25,510)               
                                                      C,66.22 H, 5.23     
                                                      N,18.17             
                                                           65.83  5.13    
                                                           18.02          
90                                                                        
    ##STR79##          81.9 dimethylformamide- water                      
                                        200-202 260(24,560)               
                                                      C,66.22 H, 5.23     
                                                      N,18.17             
                                                           65.61  5.14    
                                                           17.98          
91                                                                        
    ##STR80##          80.9 dimethylformamide- water                      
                                        190.5-193                         
                                                259(27,180)               
                                                      C,67.07 H, 5.63     
                                                      N,17.38             
                                                           66.80  5.62    
                                                           17.16          
92                                                                        
    ##STR81##          79.5 dimethylformamide- water                      
                                        178-179.5                         
                                                258(26,490)               
                                                      C,68.55 H, 6.33     
                                                      N,15.99             
                                                           68.68  6.34    
                                                           15.62          
93                                                                        
    ##STR82##          64.1 dimethylformamide- water                      
                                        202.5-205                         
                                                259(35,850)               
                                                      C,71.34 H, 4.90     
                                                      N,15.13             
                                                           71.14  4.93    
                                                           14.78          
94                                                                        
    ##STR83##          75.1 dimethylformamide- water                      
                                        189-191 278(32,130)               
                                                      C,62.94 H, 4.97     
                                                      N,17.27             
                                                           62.84  4.86    
                                                           17.22          
95                                                                        
    ##STR84##          62.3 dimethylformamide- water                      
                                        211.5-214.5                       
                                                259(30,210)               
                                                      C,61.45 H, 4.19     
                                                      N,17.91             
                                                           60.94  4.02    
                                                           17.79          
96                                                                        
    ##STR85##          75.9 dimethylformamide- water                      
                                        198-210 252(25,230)               
                                                      C,61.44 H, 3.85     
                                                      N,17.83             
                                                           61.33  3.92    
                                                           17.98          
97                                                                        
    ##STR86##          64.8 dimethylformamide- water                      
                                        232.5-234                         
                                                258(32,300)               
                                                      C,55.35 H, 3.48     
                                                      N,16.14             
                                                           55.60  3.50    
                                                           16.00          
98                                                                        
    ##STR87##          70.7 dimethylformamide- water                      
                                        237.5-239                         
                                                258(31,300)               
                                                      C,62.48 H, 4.63     
                                                      N,17.15             
                                                           62.79  4.70    
                                                           17.30          
99                                                                        
    ##STR88##          70.0 dimethylformamide- water                      
                                        229-232 256(25,630)               
                                                      C,58.10 H, 3.66     
                                                      N,16.94             
                                                           57.84  3.56    
                                                           16.90          
100                                                                       
    ##STR89##          57.6 dimethylformamide- water                      
                                        239.5-242.2                       
                                                261(37,430)               
                                                      C,53.63 H, 3.18     
                                                      N,14.71             
                                                           53.89  3.05    
                                                           14.41          
101                                                                       
    ##STR90##          50.7 dimethylformamide- water                      
                                        190-192 255(26,350)               
                                                      C,53.63 H, 3.18     
                                                      N,14.71             
                                                           53.70  2.97    
                                                           14.90          
102                                                                       
    ##STR91##          42.7 dimethylformamide- water                      
                                        202-205 375(4,200) 253(32,970)    
                                                      C,59.44 H, 4.65     
                                                      N,21.66             
                                                           59.40  4.10    
                                                           21.44          
103                                                                       
    ##STR92##          44.2 dimethylformamide- water                      
                                        237.5-239-5                       
                                                342(1,800) 264(46,530)    
                                                      C,59.44 H, 4.05     
                                                      N,21.66             
                                                           59.16  4.10    
                                                           21.31          
104                                                                       
    ##STR93##          52.3 dimethylformamide- water                      
                                        &gt;257(Dec.)                        
                                                330(20,010)               
                                                      C,59.44 H, 4.05     
                                                      N,21.66             
                                                           59.01  3.97    
                                                           21.07          
105                                                                       
    ##STR94##          35.4 dimethylformamide- water                      
                                        256.5-258                         
                                                257(33,080)               
                                                      C,53.72 H, 3.38     
                                                      N,19.57             
                                                           53.72  3.31    
                                                           19.63          
106                                                                       
    ##STR95##          57.1 dimethylformamide- water                      
                                        254- 256 (Dec.)                   
                                                256(36,930)               
                                                      C,60.53 H, 4.48     
                                                      N,20.76             
                                                           60.26  4.34    
                                                           20.68          
107                                                                       
    ##STR96##          47.3 dimethylformamide- water                      
                                        244     290(57,510)               
                                                      C,67.32 H, 4.32     
                                                      N,23.09             
                                                           67.88  4.13    
                                                           21.37          
108                                                                       
    ##STR97##          33.8 dimethylformamide- water                      
                                        227.5-229.5                       
                                                297(32,710)               
                                                      C,67.48 H, 5.03     
                                                      N,17.49             
                                                           67.49  5.05    
                                                           17.07          
191                                                                       
    ##STR98##          35.2 dimethylformamide- water                      
                                        233-236 284(16,710)               
                                                      C,73.15 H, 4.91     
                                                      N,17.06             
                                                           72.70  4.97    
                                                           16.63          
192                                                                       
    ##STR99##          25.2 dimethylformamide- methanol-water             
                                        231-232 252(32,920)               
                                                      C,56.31 H, 3.55     
                                                      N,20.52             
                                                           54.13  3.50    
                                                           20.21          
__________________________________________________________________________
 
    
     4-Alkylimidazo[1,2-a]quinoxalines (Table V) were prepared by refluxing the appropriate amide (Table I, compounds 1-33) with phosphorous oxychloride in excess pyridine during one hour. The reaction mixture was stirred into water and sufficient azeotrope removed to form a viscous residue which was dissolved in chloroform, dried over MgSO 4 , and chromatographed through an alumina column. The chloroform was evaporated and the product crystallized from the indicated solvent. 
     
                                           TABLE V                                 
__________________________________________________________________________
 ##STR100##                                                               
4-alkylimidazo[1,2-a] quinoxalines                                        
                     Recrystallization     Analysis                       
No.                                                                       
   R            % Yield                                                   
                     Solvent   m.p.°C.                             
                                     λmax.(Am)                     
                                           Calc&#39;d                         
                                                Found                     
__________________________________________________________________________
109                                                                       
   H.sup.a.     63.3 sublimed  120   316(10,900)                          
110                                                                       
   CH.sub.3     13.3 isopropyl ether                                      
                               134-135                                    
                                     312(11,200)                          
                                           C,72.11                        
                                                72.18                     
                                           H, 4.95                        
                                                 4.89                     
                                           N,22.93                        
                                                23.01                     
111                                                                       
   CH.sub.3 CH.sub.2                                                      
                37.6 hexane    114-115                                    
                                     311(10,500)                          
                                           C,73.07                        
                                                72.85                     
                                           H, 5.62                        
                                                 5.83                     
                                           N,21.30                        
                                                21.29                     
112                                                                       
   CH.sub.3 CH.sub.2 CH.sub.2                                             
                14.3 hexane    110-111                                    
                                     314(10,900)                          
                                           C,73.91                        
                                                73.99                     
                                           H, 6.20                        
                                                 6.13                     
                                           N,19.89                        
                                                19.94                     
113                                                                       
   CH.sub.3 (CH.sub.2).sub.3                                              
                17.6 hexane    92-93 324(8,000)                           
                                           C,74.64                        
                                                74.34                     
                                           H, 6.70                        
                                                 6.74                     
                                           N,18.65                        
                                                18.48                     
114                                                                       
   CH.sub.3 (CH.sub.2).sub.4                                              
                29.2 b.        63-65 314(11,300)                          
                                           C,75.28                        
                                                75.13                     
                                           H, 7.16                        
                                                 7.39                     
                                           N,17.56                        
                                                17.43                     
115                                                                       
   CH.sub.3 (CH.sub.2).sub.5                                              
                10.7 b.        43-45 313(10,800)                          
                                           C,75.86                        
                                                76.03                     
                                           H, 7.56                        
                                                 7.63                     
                                           N,16.59                        
                                                16.40                     
116                                                                       
   CH.sub.3 (CH.sub.2).sub.6                                              
                8.0  c.        54-57 313(9,400)                           
                                           C,76.37                        
                                                75.84                     
                                           H, 7.92                        
                                                 7.77                     
                                           N,15.72                        
                                                16.43                     
117                                                                       
   CH.sub.3 (CH.sub.2).sub.7                                              
                26.3 isopropyl ether                                      
                               65-66 311(11,600)                          
                                           C,76.83                        
                                                76.97                     
                                           H, 8.24                        
                                                 8.20                     
                                           N,14.93                        
                                                14.89                     
118                                                                       
   CH.sub.3 (CH.sub.2).sub.8                                              
                9.5  ethyl ether-                                         
                               55-57 307(12,500)                          
                                           C,77.25                        
                                                77.04                     
                     hexane                H, 8.53                        
                                                 8.36                     
                                           N,14.22                        
                                                14.52                     
119                                                                       
   CH.sub.3 (CH.sub.2).sub.14                                             
                24.3 isopropyl ether                                      
                               73-75 313(11,300)                          
                                           C,79.11                        
                                                79.03                     
                                           H, 9.82                        
                                                10.02                     
                                           N,11.07                        
                                                10.88                     
120                                                                       
   CH.sub.3 (CH.sub.2).sub.16                                             
                13.7 isopropyl ether                                      
                               79-81 311(11,300)                          
                                           C,79.11                        
                                                79.54                     
                                           H,10.14                        
                                                10.12                     
                                           N,10.31                        
                                                10.34                     
121                                                                       
   (CH.sub.3).sub.2 CHCH.sub.2                                            
                12.6 hexanes   52-55 314(11,700)                          
                                           C,74.64                        
                                                74.92                     
                                           H, 6.71                        
                                                 6.81                     
                                           N,18.65                        
                                                18.74                     
122                                                                       
   CF.sub.3     50.7 isopropyl ether-                                     
                               184-187                                    
                                     328(10,800)                          
                                           C,55.70                        
                                                55.94                     
                     chloroform            H, 2.55                        
                                                 2.49                     
                                           N,17.72                        
                                                17.64                     
123                                                                       
   CH.sub.2CH(CH.sub.2).sub.8                                             
                9.8  hexanes   40-42 309(13,100)                          
                                           C,78.14                        
                                                77.92                     
                                           H, 8.20                        
                                                 7.98                     
                                           N,13.67                        
                                                13.96                     
124                                                                       
    ##STR101##  16.7 ethanol   140.5-142                                  
                                     312(13,100)                          
                                           C,78.74 H,  5.05 N,16.20       
                                                78.59  5.20 16.10         
125                                                                       
   CH.sub.3 OCH.sub.2                                                     
                3.1  toluene-hexane                                       
                               96-5-97.5                                  
                                     312(10,600)                          
                                           C,67.59                        
                                                67.04                     
                                           H, 5.20                        
                                                 5.17                     
                                           N,19.71                        
                                                19.93                     
126                                                                       
    ##STR102##  14.5 ethanol   146.5-148.5                                
                                     314(10,400)                          
                                           C,74.17 H, 4.76 N,15.26        
                                                74.28  4.61 15.09         
127                                                                       
    ##STR103##  37.2 benzene   164-167                                    
                                     286(10,500)                          
                                           C,79.68 H, 4.83 N,15.49        
                                                80.38  4.91 15.12         
128                                                                       
    ##STR104##  17.9 hexane    106.5-107.5                                
                                     310(11,500)                          
                                           C,75.31 H, 5.87 N,18.82        
                                                75.32  5.84 18.75         
129                                                                       
    ##STR105##  2.0  hexane    119-120.5                                  
                                     311(11,400)                          
                                           C,76.46 H, 6.82 N,16.72        
                                                76.65  6.76 16.50         
130                                                                       
    ##STR106##  0.8  isopropyl ether                                      
                               133-135                                    
                                     312(11,700)                          
                                           C,77.39 H, 5.68 N,16.92        
                                                77.20  6.13 16.76         
__________________________________________________________________________
 Notes:                                                                   
 a. A.H. Siminov and I.G. Urykina, Khim. Geterot Soedin., 7,570(1971)     
 report this compound has an mp of 124° with                       
 λ.sub.max.sup.MeOH  (Am)II 315 (10,700).                          
 b. Purified by sublimation at 90°/0.15 mm Pressure.               
 c. Purified by distillation at 174-184°/0.40 mm P.                
 
    
     4-Arylimidazo[1,2-a]quinoxalines (Table VI) were prepared and isolated according to the general method described for the 4-alkylimidazo[1,2-a]quinoxalines, except as noted in Table VI. 
     
                                           TABLE VI                                
__________________________________________________________________________
 ##STR107##                                                               
4-Arylimidazo(1,2-a)quinoxalines                                          
                     %   Crystallization       Analysis                   
No.                                                                       
   Ar                Yield                                                
                         Solvent   m.p. °C.                        
                                         λmax. (Am)                
                                               Calc&#39;d                     
                                                    Found                 
__________________________________________________________________________
131                                                                       
    ##STR108##       34.8                                                 
                         benzene   145-147                                
                                         328(14,100)                      
                                               C,78.35 H,                 
                                                    78.70  4.38 16.90     
132                                                                       
    ##STR109##       37.2                                                 
                         toluene- isopropanol                             
                                   149-150.5                              
                                         334(22,650)                      
                                               C,79.74 H,                 
                                                    78.89  5.08 16.27     
133                                                                       
    ##STR110##       35.9                                                 
                         isopropanol- isopropyl ether                     
                                   112-114                                
                                         329(15,400)                      
                                                C,78.74 H,                
                                                    78.53  5.19 16.20     
134                                                                       
    ##STR111##       47.1                                                 
                         isopropanol                                      
                                   119-120                                
                                         329(18,100)                      
                                               C,78.74 H,                 
                                                    78.32  4.73 15.93     
135                                                                       
    ##STR112##       37.8                                                 
                         isopropanol                                      
                                   136-137                                
                                         331(27,780)                      
                                               C,82.22 H,                 
                                                    82.06  4.38 12.89     
136                                                                       
    ##STR113##       47.0                                                 
                         isooctane 112-113                                
                                         332(10,411)                      
                                               C,65.18 H,                 
                                                    65.03  3.10 13.62     
137                                                                       
    ##STR114##       56.7                                                 
                         hexanes   105-107                                
                                         329(20,354)                      
                                               C,79.70 H,                 
                                                    79.59  6.58 13.84     
138                                                                       
    ##STR115##       37.2                                                 
                         isopropanol- toluene                             
                                   149-150.5                              
                                         334(22,650)                      
                                               C,74.17 H,                 
                                                    74.18  4.79 15.33     
139                                                                       
    ##STR116##       51.5                                                 
                         isopropanol                                      
                                   136-138                                
                                         329(16,600)                      
                                               C,70.81 H,                 
                                                    70.61  5.06   13.56   
140                                                                       
    ##STR117##       31.5                                                 
                         ethanol   173-175                                
                                         328(15,280)                      
                                               C,68.70 H,                 
                                                    69.06  3.28 15.08     
141                                                                       
    ##STR118##       6.8 benzene- hexanes                                 
                                   166-168                                
                                         331(10,300)                      
                                               C,68.70 H,                 
                                                    68.77  3.48 14.87     
142                                                                       
    ##STR119##       35.2                                                 
                         isopropanol                                      
                                   133-134                                
                                         330(14,000)                      
                                               C,68.70 H,                 
                                                    68.43  3.45 14.89     
143                                                                       
    ##STR120##       61.9                                                 
                         toluene   215-217.5                              
                                         333(16,530)                      
                                               C,61.16 H,                 
                                                    60.94  2.82 13.50     
144                                                                       
    ##STR121##       3.4 carbon tetra- chloride                           
                                   168-170                                
                                         321(13,030)                      
                                               C,61.17 H,                 
                                                    60.61  2.85 13.57     
145                                                                       
    ##STR122##       24.1                                                 
                         dimethylformamide- water                         
                                   161.5-164.5                            
                                         319(10,200)                      
                                               C,59.28 H,                 
                                                    58.75  3.03 12.90     
146                                                                       
    ##STR123##       13.4                                                 
                         dimethylformamide- water                         
                                   172   329(12,900)                      
                                               C,59.28 H,                 
                                                    59.34  3.13 13.23     
147                                                                       
    ##STR124##       39.1                                                 
                         isopropanol                                      
                                   183-185                                
                                         328(14,500)                      
                                               C,72.99 H,                 
                                                    73.00  4.06 15.77     
148                                                                       
    ##STR125##       15.0                                                 
                         ethanol   190-192                                
                                         222(48,000)                      
                                               C,70.58 H,                 
                                                    70.54  3.71 14.67     
149                                                                       
    ##STR126##       53.3                                                 
                         dimethylformamide- water                         
                                   257.5-259.5                            
                                         335(14,900)                      
                                               C,75.54 H,                 
                                                    75.15  3.85 20.66     
150                                                                       
    ##STR127##       59.8                                                 
                         2-ethoxyethanol                                  
                                   220.5-222.5                            
                                         333(13,850)                      
                                               C,66.20 H,                 
                                                    66.10  3.48 19.53     
151                                                                       
    ##STR128##       40.3                                                 
                         toluene   249-252                                
                                         346(15,269)                      
                                               C,66.20 H,                 
                                                    66.10  3.44 19.28     
152                                                                       
    ##STR129##       52.5                                                 
                         dimethylformamide                                
                                   283-285                                
                                         340(10,880)                      
                                               C,57.30 H,                 
                                                    57.08  2.74 21.11     
153                                                                       
    ##STR130##       75.7                                                 
                         dimethylformamide- water                         
                                   198-199.5                              
                                         369(23,470)                      
                                               C,73.83 H,                 
                                                    73.48  4.69 21.54     
154                                                                       
    ##STR131##       61.9                                                 
                         dimethylformamide- water                         
                                   130-133                                
                                         326(14,830)                      
                                               C,73.83 H,                 
                                                    73.56  4.78 21.69     
155                                                                       
    ##STR132##       58.0                                                 
                         ethylacetate- hexane                             
                                   214-217                                
                                         342(27,700)                      
                                               C,68.88 H,                 
                                                    68.46  4.99 17.76     
156                                                                       
    ##STR133##       13.9                                                 
                         dimethylformamide- water                         
                                   237.5-240                              
                                         345(32,350)                      
                                               C,68.24 H,                 
                                                    68.54  3.90 14.00     
173                                                                       
    ##STR134##       32.3                                                 
                         ethanol   155-157                                
                                         321(13,090)                      
                                                C,72.99 H,                
                                                    72.44 3/83 16.14      
157                                                                       
    ##STR135##       56.6                                                 
                         dimethylformamide- water                         
                                   134.5-136                              
                                         332(14.260)                      
                                               C,59.28 H, 3.11 N,12.96    
                                                    59.25  3.04 13.11     
158                                                                       
    ##STR136##       47.5                                                 
                         dimethylformamide- water                         
                                   132.5-134                              
                                         330(13,970)                      
                                               C,72.99 H, 3.83 N,15.96    
                                                    73.00  3.79 15.04     
159                                                                       
    ##STR137##       52.7                                                 
                         ethanol   113-114.5                              
                                         329(16,500)                      
                                               C,74.17 H, 4.76 N,15.26    
                                                    74.09  4.71 15.05     
160                                                                       
    ##STR138##       10.62                                                
                         chloroform                                       
                                   159-161.5                              
                                         323(15,290)                      
                                               C,81.34 H, 4.43 N,14.23    
                                                    81.29  4.41 14.22     
161                                                                       
    ##STR139##       43.2                                                 
                         benzene   154.5-156.5                            
                                         340(21,800)                      
                                               C,81.34 H, 4.44 N,14.23    
                                                    81.19  4.57 13.92     
162                                                                       
    ##STR140##       25.4                                                 
                         isopropanol                                      
                                   210-215                                
                                         343(23,800)                      
                                               C,68,81 H, 4.69 N,15.04    
                                                    68.99  4.63 14.92     
163                                                                       
    ##STR141##       84.2                                                 
                         ethanol   150-160                                
                                         333(14,950)                      
                                               C,71.28 H, 4.32 N,13.85    
                                                    71.31  4.44 13.85     
164                                                                       
    ##STR142##       80.3                                                 
                         ethanol   116-118                                
                                         335(15,100)                      
                                               C,72.49 H, 5.17 N,12.68    
                                                    72.38  5.42 12.36     
165                                                                       
    ##STR143##       62.6                                                 
                         ethanol   90.5-93.5                              
                                         335(15,100)                      
                                               C,75.15 H, 7.03 N,10.11    
                                                    74.87 7.16 9.94       
166                                                                       
    ##STR144##       45.85                                                
                         chloroform                                       
                                   154-155.5                              
                                         344(27,240)                      
                                               C,76.38 H, 8.51 N,11.14    
                                                    76.58  8.35 10.81     
193                                                                       
    ##STR145##       29.80                                                
                         ethanol   150-152                                
                                         342(22,900)                      
                                               C,74.72 H, 5.23 N,14.52    
                                                    74.37  5.17 14.33     
196                                                                       
    ##STR146##       0.2 dimethylformamide- water                         
                                   178-181                                
                                         330(27,300)                      
                                               C,51.77 H, 2.72            
                                                    51.89  2.68 11.46     
219                                                                       
    ##STR147##       37.1                                                 
                         toluene   151.5-153.5                            
                                         333(21,000)                      
                                               C,78.32 H, 4.48 N,12.45    
                                                    78.32  4.63 12.22     
220                                                                       
    ##STR148##       35.1                                                 
                         benzene   151.5-153.5                            
                                         337(22,200)                      
                                               C,75.19 H, 4.66 N,11.44    
                                                    75.42  4.58 11.46     
221                                                                       
    ##STR149##       33.3                                                 
                         ethanol-water                                    
                                   &gt; 300 343(22,700)                      
                                               C,72.92 H, 4.45 N,11.60    
                                                    73.21  4.31 11.74     
222                                                                       
    ##STR150##       28.2                                                 
                         ethanol   83-85 348(24,600)                      
                                               C,72.04 H, 5.74 N,12.60    
                                                    71.64  5.68 12.62     
194                                                                       
    ##STR151##       22.6                                                 
                         toluene   164-165.5                              
                                         339(19,400)                      
                                               C,68.05 N, 5.11 N,12.53    
                                                    67.70  5.03  12.32    
 Notes To Table VI:                                                       
 a. U.S. Pat. No. 3,887,566 describes this compound as having a m.p. of   
 154-157° C.                                                       
 b. Prepared by refluxing equimolar amounts of the 2aminophenylimidazole  
 and phthalic anlydride in toluene for one and onehalf hours. Upon cooling
 the product separated out of solution.                                   
 c. Prepared by catalytic hydrogenation with 10% palladium on carbon of a 
 dimethylformamide solution of the nitro analog, crude product precipitate
 with water.                                                              
 d. Prepared by treating compound 153 in pyridine with the appropriate aci
 chloride followed by precipitation with water.                           
 e. Prepared by HI cleavage of compound No. 138.                          
 f. Prepared by treating the lithium salt of compound No. 162 with the    
 appropriate acid chloride in DMF followed by precipitation with water.   
 g. Prepared by treating compound No. 151 with the appropriate nucleophils
 according to the method of Kornblum at at. J. Org. Chem., 41,1560(1976). 
 h. Prepared by HI cleavage of compound 220.                              
 
    
     The 4-Alkylaminoimidazo[1,2-a]quinoxalines (Table VII) were prepared by treating the corresponding alkylureylenes (Table III) with phosphorous oxychloride and pyridine during one-half hour at reflux temperatures. The reaction mixture was poured into cold water and the excess pyridine was removed by azeotropic distillation. The crude product was dissolved in chloroform and pass through an alumina columa. After evaporation of the chloroform, the solid was crystallized from the indicated solvent and obtained in the indicated yield. 
     
                                           TABLE VII                               
__________________________________________________________________________
 ##STR152##                                                               
4-Alkylaminoimidazo(1,2-a)quinoxalines                                    
            %   Crystallization     Analysis                              
No.                                                                       
   R        Yield                                                         
                Solvent m.p. °C.                                   
                             λmax. (Λm)                     
                                    Calc&#39;d                                
                                        Found                             
__________________________________________________________________________
167                                                                       
    ##STR153##                                                            
            4.89                                                          
                hexane  98.5-101.5                                        
                             335(11,700)                                  
                                    C,72.15 H, 6.81 N,21.04               
                                        72.02  6.75 20.81                 
168                                                                       
   CH.sub.3 (CH.sub.2).sub.2 CH.sub.2                                     
            28.33                                                         
                isopropyl ether                                           
                        102-104                                           
                             332(11,480)                                  
                                    C,69.97                               
                                        70.12                             
                                    H, 6.71                               
                                        6.71                              
                                    N,23.31                               
                                        23.21                             
169                                                                       
   CH.sub.3 (CH.sub.2).sub.2                                              
            7.5 isopropyl ether                                           
                        72-74                                             
                             317(15,800)                                  
                                    C,69.00                               
                                        69.14                             
                                    H, 6.24                               
                                        6.35                              
                                    N,24.76                               
                                        24.60                             
__________________________________________________________________________
 
    
     4-Arylaminoimidazo[1,2-a]quinoxalines (Table VIII) were prepared by treating the corresponding arylureylenes (Table IV) with an equimolar amount of phosphorous oxychloride in refluxing pyridine during one hour. The cooled reaction mixture was stirred into cold water, and the crude solid which separated was dissolved in chloroform, dried and passed through an alumina column. The chloroform was evaporated and the crude solid was crystallized as indicated in Table VIII. 
     
                                           TABLE VIII                              
__________________________________________________________________________
 ##STR154##                                                               
4-Arylaminoimidazo(1,2-a)quinoxalines                                     
                     %   Crystallization        Analysis                  
No.                                                                       
   Ar                Yield                                                
                         Solvent    m.p.°C.                        
                                          λmax.(Am)                
                                                Calc&#39;d                    
                                                    Found                 
__________________________________________________________________________
170                                                                       
    ##STR155##       7.2 ethanol-water                                    
                                    120-123                               
                                          304(13,800)                     
                                                C,72.57 H, 4.76 N,21.16   
                                                    72.67  4.71 20.88     
171                                                                       
    ##STR156##       13.1                                                 
                         methanol- chloroform                             
                                    151   334(20.700)                     
                                                C,74.43 H, 5.14 N,20.42   
                                                    74.16  5.06 20.09     
172                                                                       
    ##STR157##       11.7                                                 
                         methanol- chloroform                             
                                    153-155                               
                                          330(20,200)                     
                                                C,74.43                   
                                                    73.23  5.26 20.02     
174                                                                       
    ##STR158##       13.6                                                 
                         methanol- chloroform                             
                                    176.5-178                             
                                          330(22,200)                     
                                                C,65.26 H, 3.75 N,19.02   
                                                    65.04  3.77 18.91     
175                                                                       
    ##STR159##       10.9                                                 
                         methanol- chloroform                             
                                    178.5-180.5                           
                                          344(33,600)                     
                                                C,58.38 H, 3.06 N,17.02   
                                                    50.15  3.06 17.09     
176                                                                       
    ##STR160##       18.2                                                 
                         toluene- chloroform                              
                                    193.5-195                             
                                          332(4,500)                      
                                                C,49.76 H, 2.87 N,14.51   
                                                    49.72  3.10 14.39     
177                                                                       
    ##STR161##       11.5                                                 
                         ethanol    196.5-198.5                           
                                          324(16,600)                     
                                                C,56.66 H, 3.27 N,16.52   
                                                    56.69  3.24 16.43     
178                                                                       
    ##STR162##       15.0                                                 
                         methanol- chloroform                             
                                    184-185.5                             
                                          329(24,100)                     
                                                C,56.66 H, 3.27 N,16.52   
                                                    56.26  3.20 16.54     
179                                                                       
    ##STR163##       10.52                                                
                         dimethylformamide water                          
                                    122-124                               
                                          343(19,600)                     
                                                C,63.27 H,                
                                                    62.94  4.19 18.58     
180                                                                       
    ##STR164##       13.0                                                 
                         ethanol-dimethyl- formamide                      
                                    139   339(19,810)                     
                                                C,69.05 H, 3.98 N,20.13   
                                                    68.88  4.02 20.13     
181                                                                       
    ##STR165##       9.4 isopropanol                                      
                                    148.5-149.5                           
                                          343(20,230)                     
                                                C,69.05 H, 3.98 N,20.13   
                                                    68.92  4.00 20.14     
182                                                                       
    ##STR166##       3.1 isopropanol                                      
                                    139.5-141                             
                                          331(18,030)                     
                                                C,69.05 H, 3.98 N,20.13   
                                                    68.50  3.92 19.86     
183                                                                       
    ##STR167##       16.58                                                
                         dimethylformamide- water                         
                                    166-168.5                             
                                          347(21,730)                     
                                                C,56.66 H, 3.27 N,16.52   
                                                    56.31  3.25 16.56     
184                                                                       
    ##STR168##       11.4                                                 
                         dimethylformamide- water                         
                                    207-209                               
                                          366(22,410)                     
                                                C,70.33 H, 4.86 N,19.30   
                                                    70.61  5.11 19.11     
185                                                                       
    ##STR169##       8.3 dimethylformamide water                          
                                    116.5-117.5                           
                                          335(21,820)                     
                                                C,70.33 H, 4.86 N,19.30   
                                                    70.16  5.28 19.31     
186                                                                       
    ##STR170##       14.12                                                
                         dimethylformamide- water                         
                                    147-149                               
                                          339(18,540)                     
                                                C,70.33 H, 4.86 N,19.30   
                                                    70.14  4.98 19.09     
187                                                                       
    ##STR171##       2.0 isopropanol-dimethyl- formamide                  
                                    195-197                               
                                          341(20,370)                     
                                                C,60.28 H, 3.95 N,21.97   
                                                    60.21  3.88 21.63     
188                                                                       
    ##STR172##       36.4                                                 
                         dimethylformamide- water                         
                                    241-243.5                             
                                          400(8,960)                      
                                                C,62.95 H, 3.63 N,22.94   
                                                    62.62  3.63  22.68    
189                                                                       
    ##STR173##       33.1                                                 
                         dimethylformamide- water                         
                                    323-324.5                             
                                          368(23,670)                     
                                                C,62.95 H, 3.63 N,22.94   
                                                    62.73  3.73 22.81     
195                                                                       
    ##STR174##       11.61                                                
                         dimethylformamide- water                         
                                    138.5-141                             
                                          335(22,900)                     
                                                C,74.99 H, 4.58 N,15.90   
                                                    75.02  4.66 75.02     
197                                                                       
    ##STR175##       5.52                                                 
                         dimethylformamide- water                         
                                    143- 145                              
                                          330(18,000)                     
                                                C,74.43 H, 5.15 N,20.42   
                                                    74.63  5.16 20.09     
198                                                                       
    ##STR176##       10.91                                                
                         dimethylformamide                                
                                    163.5-165.5                           
                                          337(18,800)                     
                                                C,74.98 H, 5.59 N,19.43   
                                                    74.69  5.56 19.43     
199                                                                       
    ##STR177##       15.29                                                
                         dimethylformamide- water                         
                                    81-83 333(20,800)                     
                                                C,73.83 H, 5.51 N,19.13   
                                                    73.87  5.49 18.88     
200                                                                       
    ##STR178##       13.81                                                
                         dimethylformamide- water                         
                                    124.5-127                             
                                          335(23,200)                     
                                                C,73.83 H, 5.51 N,19.13   
                                                    74.14  5.47 19.02     
201                                                                       
    ##STR179##       16.96                                                
                         isopropanol- water                               
                                    89.5-91.5                             
                                          335(21,000)                     
                                                C,73.83 H, 5.51 N,19.13   
                                                    74.14  5.47 19.02     
202                                                                       
    ##STR180##       11.50                                                
                         methanol- chloroform                             
                                    187-190                               
                                          342(24,200)                     
                                                C,76.29 H, 4.56 N,17.80   
                                                    76.58  4.52 17.58     
203                                                                       
    ##STR181##       12.50                                                
                         dimethylformamide- water                         
                                    120.5-123                             
                                          340(20,300)                     
                                                C,68.99 H, 5.15 N,17.88   
                                                    68.32  5.32 17.61     
204                                                                       
    ##STR182##       21.39                                                
                         dimethylformamide- water                         
                                    102.5-107                             
                                          340(19,600)                     
                                                C,62.20 H, 3.38 N,17.07   
                                                    61.56  3.34 17.46     
205                                                                       
    ##STR183##       8.5 dimethylformamide- water                         
                                    90-97 341(26,400)                     
                                                C,65.68 H, 4.62 N,18.02   
                                                    65.56  4.57 17.88     
206                                                                       
    ##STR184##       21.39                                                
                         dimethylformamide- water                         
                                    129-130                               
                                          347(20,300)                     
                                                C,62.20 H, 3,38 N,17.07   
                                                    61.56  3.34 17.46     
207                                                                       
    ##STR185##       11.49                                                
                         dimethylformamide- water                         
                                    178.5-179.5                           
                                          324(25,500)                     
                                                C,56.29 H, 2.78 N,15.45   
                                                    55.86  2.72 15.37     
208                                                                       
    ##STR186##       7.52                                                 
                         dimethylformamide- water                         
                                    172.5-173.5                           
                                          345(24,900)                     
                                                C,56.29 H, 2.78 N,15.45   
                                                    55.86   2.72 15.37    
209                                                                       
    ##STR187##       15.18                                                
                         dimethylformamide- water                         
                                    170-172                               
                                          332(23,800)                     
                                                C,65.18 H, 4.18 N,17.89   
                                                    65.35  4.15 17.91     
210                                                                       
    ##STR188##       13.56                                                
                         dimethylformamide- water                         
                                    171.5-173                             
                                          337(17,300)                     
                                                C,64.86 H, 3.40 N,18.91   
                                                    64.92  3.51 19.09     
211                                                                       
    ##STR189##       10.78                                                
                         dimethylformamide- water                         
                                    259.5-261.5                           
                                          342(23,200)                     
                                                C,56.82 H, 3.28 N,16.57   
                                                    56.76  3.07 16.57     
212                                                                       
    ##STR190##       7.22                                                 
                         dimethylformamide- water                         
                                    198-200                               
                                          343(18,400)                     
                                                C,61.45 H, 3.22 N,17.92   
                                                    61.35  3.27 17.81     
213                                                                       
    ##STR191##       3.04                                                 
                         methanol-chloroform                              
                                    229-231                               
                                          341(19,900)                     
                                                C,58.63 H, 3.15 N,21.36   
                                                    58.50   3.06 21.20    
214                                                                       
    ##STR192##        4.10                                                
                         methanol-chloroform                              
                                    168-170                               
                                          344(21,400)                     
                                                C,63.06 H, 4.12 N,21.63   
                                                    62.97  4.08 21.34     
215                                                                       
    ##STR193##       19.43                                                
                         dimethylformamide- water                         
                                    271-273                               
                                          346(19,600)                     
                                                C,56.57 H, 2.97 N,20.61   
                                                    56.44  2.90 20.51     
216                                                                       
    ##STR194##        5.96                                                
                         dimethylformamide- water                         
                                    224-226.5                             
                                          349(34,700)                     
                                                C,70.48 H, 3.91 N,24.17   
                                                    70.89  3.94 24.09     
218                                                                       
    ##STR195##        2.31                                                
                         isopropanol                                      
                                    95-96.5                               
                                           --   C,75.47 H, 6.00 N,18.53   
                                                    75.08  6.34 18.53     
__________________________________________________________________________
 
    
     Various compounds of this invention display antifungal and anti-yeast activity. Thus, for example, they have been found to be effective against such organisms as Candida albicans (ATCC No. 10231), Candida tropicalis, Aspergillus niger (ATCC No. 16404), Trichophyton mentagrophytes (ATCC No. 8757 and 9129), Trichopyton rubrum (ATCC No. 10218 and 14001) and Trichophyton ajelloi. 
     The antifungal activity of compounds of this invention indicate their usefulness against dermatomycosis such as tinea capitis, tinea favosa, tinea barbae, tinea corporis, tinea imbricata, tinea cruris, tinea pedis, tinea manus, tinea unquium and various types of candidiasis such as glossitis, stomatitis, chelitis, perleche, vaginitis and balanitis. 
     When the compounds of the present invention are used for antifungal medical purposes, they will usually be incorporated in a suitable pharmaceutical carrier. These antifungal preparations may take the form of solutions, lotions, creams, ointments, etc. The quantity of antifungal agent of this invention that will be contained in such preparations may vary somewhat. Ordinarily, however, it will constitute about 0.5% to 10.0% by weight based on the total weight of the preparation. 
     In Table IX below are listed the antifungal activity of a number of compounds encompassed in the present invention. These were determined by the agar dilution method as described in Chapters 2 and 3 of Methods in Microbiology, Vol. 7B, edited by J. R. Norris and D. W. Ribbons, Academic Press, New York, 1972. 
     
                       TABLE IX                                                    
______________________________________                                    
Antifungal Activity                                                       
Parts Per Million Inhibitions of                                          
Fungus and Yeast Species                                                  
Com-                               I.                                     
pound C.       C.       A.   T.    mentagro-                              
                                           T.                             
No.   albicans tropicalis                                                 
                        niger                                             
                             ajelloi                                      
                                   phytes  rubrum                         
______________________________________                                    
 20                          100   100                                    
136                                100                                    
 40   100      100           100   100                                    
 35                          100    16                                    
 39                          100   100                                    
133   100      100            8     8      8                              
134                          100    16                                    
139                                100                                    
137                          100   100                                    
135                          100   100                                    
142                                100                                    
132                          100   100                                    
138                          100   100                                    
130   100      100           100   100                                    
113   100      100                 100                                    
 9                                  16     16                             
 10                                 16     16                             
116                                 16     16                             
127                                 16     16                             
109                                128     32                             
114                                 16     1                              
113                                256     4                              
123                                        2                              
131                                 16     2                              
140                                        &lt;0.5                           
151                                        1                              
119                                        8                              
120                                        1                              
 8                                  8      8                              
 16                                 4      2                              
110                     128        128     64                             
122                                        32                             
112                                128     64                             
163            100                                                        
124   100      100           100   100     8                              
 58                          100   100     100                            
 59                                        100                            
 62                          100   100     100                            
126                          100   100     100                            
145                          100   100     100                            
159                          100   100     100                            
160                          100   100     100                            
163                          100   100     100                            
164                          100   100     100                            
165                          100   100     100                            
167                          100   100     100                            
168                          100   100     100                            
169                          100   100     100                            
173                          100   100     100                            
179                          100   100     100                            
182                          100   100     100                            
184                          100   100     100                            
185                          100   100     100                            
186                          100   100     100                            
189                          100           100                            
187                          100           100                            
128                                        16                             
129                           16    16     8                              
______________________________________                                    
 
    
     A number of the compounds encompassed in the present invention have been found to have immunosuppressant action. Of those tested, most of these are of the 4-substituted imidazo[1,2-a]quinoxaline type described in formula I above, although a couple are of the 1-(2-acylaminophenyl)imidazole type shown in formula II. Because they exhibit this activity, they are indicated for use in the treatment of those diseases that the prior art recognizes may be helped by the administration of immunosuppressants. These include such conditions as: glomerulonephritis, serum sickness, organ transplant, rheumatoid arthritis, systemic lupus erythematosis, ulcerative colitis, chronic active hepatitis, multiple sclerosis, heterografts or homografts in burns, psoriatic arthritis, urticaria, respiratory allergies, i.e. asthma, hayfever; scleraclerma, mycosis fungoides, dermatomyositis, psoriasis and contact dermatitis (including poison ivy). 
     The dosage level for administering the immunosuppressants of the present invention will vary with the particular compound that is to be administered. In general, this will be at about the same level of the prior art immunosuppressants. For the most part, when the present immunosuppressants are administered orally or intraveneously, the daily dose would be in the range of about 0.1 mg. to 15 mg./per kilogram of body weight. When other mode of administration are employed, e.g. depot injections, implants, etc. the dose may be considerably higher i.e. up to about 100 mg./kg of body weight in a single injection. 
     The immunosuppressant activities of the compounds of this invention were determined via the hemolysin test in mice and by the delayed hypersensitivity test. The hemolysin test used is that described in Methods in Immunology, edited by D. H. Campbell et al, W. A. Benjamin, New York 1963  pages 172-175, and measures humeral or antibody response. The delayed hypersensitivity test measures the effect of a test compound on the ability of a subject mouse to mount a cell-mediated immune response to the antigen, Mycobacterium tuberculosis H37Ra. The mouse is sensitized to the antigen by subcutaneous administration in the base of the tail. The development of the delayed hypersensitivity response may be measured at any time beginning six days after sensitization but is usually done on the ninth day as follows: The right hind paw is injected with purified protein derivative (tuperculin) while the left hind paw (control) receives physiological saline. Both paw volumes are measured after twenty-four hours and significant increase in the volume of the right hind paw is taken as a measure of an effective delayed hypersensitivity response. All compounds were administered by the subcutaneous route. 
     The results of these studies are summarized in Table X below. The expression HL(ED 50 ) mg./kg s.c. is an expression of the number of milligrams per kilogram of body weight of the drug administered subcutaneously required to reduce the antibody activity by 50% when compared with a control. In this case, the lower the HL(ED 50 ) value for a drug the more effective immunosuppressant it is. 
     The D.H.S. (ED 60 ) mg./kg. s.c. value appearing in column 3 is an expression of the effectiveness of the drug in reducing the edema that accompanies the cell-mediated immune response. It is a measure of the number of milligrams per kilogram of body weight of the drug administered subcutaneously which is required to reduce the edema of the cell-mediated immune response by 60% when compared to the control. Again, the lower the D.H.S. (ED 60 ) value the more effective is the drug as an immunosuppressant for the cell-mediate immune response. 
     
                       TABLE X                                                     
______________________________________                                    
Compound      HL(ED.sub.50)                                               
                          D.H.S. (ED.sub.60)                              
No.           mg/kg. s.c. mg/kg. s.c.                                     
______________________________________                                    
151           0.3         1.52                                            
140           0.26        1.15                                            
131           18          81                                              
116           &gt;50         56                                              
117           &gt;50         46                                              
118           &gt;50         43                                              
109           &gt;50         &gt;50                                             
110           --          50                                              
 3            50          50                                              
 66           46          &gt;50                                             
147           0.027       1.7                                             
134           0.5         7.2                                             
137           &gt;0.125      3.2                                             
135           0.033       0.22                                            
142           0.20        4.2                                             
136           2.7         &gt;50                                             
133           0.75        32                                              
139           3.0         &gt;50                                             
138           0.72        27                                              
127           &gt;50         36                                              
170           6.6         &gt;50                                             
150           22          &gt;50                                             
143           0.36        1.3                                             
174           0.61        8.0                                             
171           0.96        59.0                                            
175           0.09        5.9                                             
178           11.0        46.0                                            
196           0.42        45.0                                            
197           1.6         37                                              
 3            50.0        50.0                                            
169           46          &gt;50.0                                           
146           0.11        3.1                                             
153           1.2         5.7                                             
149           0.16        8.8                                             
126           35.0        &gt;50.0                                           
177           13.0        &gt;50.0                                           
182           1.1         --                                              
162           13.0        --                                              
173           --          40                                              
159           3.0         27                                              
181           16.0        --                                              
180           5.6         --                                              
183           0.39        15                                              
158           1.0         7.6                                             
157           0.39        12                                              
218           1.5         25                                              
219           2.5         &gt;32                                             
220           2.3         11                                              
222           1.0         &gt;32                                             
______________________________________                                    
 &gt;50 means that it would take more than 50 mg./kg. of drug to reduce the  
 humeral antibody activity by 50% or to reduce edema of the cell mediated 
 immune response by 60%. Since these values are higher than is of practica
 interest from a clinical point of view, no further testing was doe for   
 these materials.                                                         
 
    
     A number of compounds encompassed in the present invention display non-steroidal anti-inflammatory properties. This appears to be generally the case for the 4-substituted imidazo[1,2-a]quinoxalines of formula 1 above and the 1-(2-acylaminophenyl)imidazoles of formula II. Because of this characteristic, they are indicated for use in the treatment of diseases that the prior art recognizes may be helped by the administration of non-steroidal anti-inflammatory compounds. These include such conditions as ichthyosis, psoriasis, alopecia, atopic eczemas, etc. 
     The dosage level for administering the anti-inflammatory agents of the present invention may vary somewhat depending on the particular drug selected, the disease being treated and the mode of administration. In general, however, when used for topical application, the compounds are distributed in a pharmaceutical vehicle suitable for topical application. In these compositions, the anti-inflammatory agent of this invention will comprise about 0.5% to 15.0% by weight based on the total weight of the composition. 
     The anti-inflammatory agents of the present invention may also be administered orally, intraveneously, subcutaneously, intramuscularly, and intradermally. In these cases, the daily dosage will be in the range of from 0.5 mg. to 20 mg. per kilogram of body weight of the active anti-inflammatory agents of this invention. 
     The anti-inflammatory activity of representative compounds of this invention was determined by the rat paw edema assay both by local administration (Table XI below) and by oral dosing (Table XII below). For the oral dosing, the procedure of C. A. Winter, E. A. Risley and G. W. Nuss, Proc. Soc. Exp. Biol. Med. 111, 544 (1962) was employed with measurement taken four hours after the drug was administered. The local administration tests were carried out similarly except the irritant (carrageenan) and the test compound were injected simultaneously at time zero. 
     Tables XI and XII report the anti-inflammatory activity of the compounds tested as % difference in the edema or swelling as compared with the control. These Tables also give the response in many instances of more than one dose level of the same drug. 
     
                       TABLE XI                                                    
______________________________________                                    
Rat Paw Edema Assay, -Local Administration                                
(injected directly into paw)                                              
% Difference from Control                                                 
Compound No.                                                              
            1 mg     10 mg    100 mg 100 mg/kg                            
______________________________________                                    
148         -32.6    -53.5    -14.3  -39                                  
109         -30.3    -3.9     +31.6                                       
114         -68.2    -30.0    -131.6                                      
117                                                                       
110                                  -74                                  
122                                  -61                                  
 49                                  -35                                  
 7                                   -22                                  
 51                                  -57                                  
140                                  -78                                  
______________________________________                                    
 
    
     
                       TABLE XII                                                   
______________________________________                                    
Rat Paw Edema Assay, Oral Dosing                                          
              %Difference from Control                                    
Compound No.    100 mg/kg   400 mg/kg                                     
______________________________________                                    
Indomethacin    -65                                                       
phenybutazone   -76                                                       
Aspirin         -57                                                       
114             -61                                                       
110             -43                                                       
122             -61                                                       
148             -52                                                       
 49             -35                                                       
 7              -52                                                       
 51             -57                                                       
140             -35                                                       
131             -52                                                       
 10             -30                                                       
 39             -50                                                       
133             -17                                                       
137             -26                                                       
112             -17         -68                                           
111             -43                                                       
121             -61                                                       
147             -39                                                       
134             -43                                                       
139             -22         -25                                           
132             -76                                                       
150             -30                                                       
144             -26                                                       
115             +70         -25                                           
117             -7          -18                                           
123             0           -50                                           
116             +104        -18                                           
136             -9          -25                                           
 8              -22         -13                                           
 29             -24         -25                                           
 14             -52                                                       
 20             -59                                                       
 38             -41                                                       
 57             -35                                                       
 50             -20         -33                                           
 45             -33                                                       
 40             -43                                                       
 35             -50                                                       
 37             -35                                                       
 18             -28                                                       
 15             -24         -5                                            
 55             -26                                                       
 52             -26                                                       
 2              -26         +43                                           
 23             -46                                                       
 25             -30                                                       
 30             +3          -33                                           
 36             -7          -68                                           
 42             -9          -25                                           
 24             -17         -25                                           
109             -17                                                       
 71             -22                                                       
 75             -30                                                       
 68             -26                                                       
 73             -22                                                       
128             -39                                                       
129             -30                                                       
______________________________________