Imidazole thio

N — N — — Imidazole 4,5-di-t-butylimidazole histamine dihydrochloride 2-thio-hydantoin... 

Chemical Name N-cyano-N -methyl,N"-[2-[ [(5-methyl-1 H-imidazol-4-yl)methyl] thio] ethyl] guanidine... 

CN ( )-l-[2-[[(4-chlorophenyl)methyl]thio]-2-(2,4-dichlorophenyl)ethyl]-177-imidazole mononitrate... 

C5H5N3 98873-55-3) see Lanoconazole A -cyano-Ai -[2-([(5-methyl-lH-imidazol-4-yl)mcthylJ-thio]ethyl]carbamimidothioic acid methyl ester (C, H 5N5S2 52378-40-2) see Cimetidine... 

The 4(5)-amino-2-substituted imidazoles (45) and (46) have been prepared (50JCS2775) by condensation of aminoacetonitrile (30) with the thio-iminoether hydrochloride salts (40) and (41), respectively. These 4(5)-aminoimidazoles (45, 46) were isolated as their hydrochloride salts in yields of 36 and 90% (Scheme 3). 

Several pyrrolo[l,2-f] imidazoles have been studied for their physiological activities. Most of these compounds demonstrated a high affinity for the 5-HT1A receptor. Pyrrolo[l,2-o]imidazoles are present in the literature as tetrahydro, perhydro, 1-oxoperhydro, 3-oxoperhydro, 7-oxoperhydro, 1,3-dioxoperhydro, 1,5-dioxoperhydro, 2,7-dioxoperhydro, and 1 -thio-3-oxoperhydro derivatives. 

Butoconazole Bntoconazole, l-[4-(4-chlorophenyl)-2-[(2,6-dichlorophenyl)thio]butyl]-IH-imidazole (35.2.12), is synthesized from 4-chlorobenzylmagnesium bromide, which is reacted with epichloridrine to make 4-(4 -chlorophenyl)-l-chlorobutan-2-ol (35.2.10), which is reacted with imidazole in the presence of sodium to make 4-(4 -chlorophenyl)-l-(lH-imidazolyl)butanol-2 (35.2.11). The hydroxyl group in the last is replaced with a chlorine atom npon reaction with thionyl chloride, which is then by the reaction with 2,6-dichlorothiophenol bntoconazole [27,28], is obtained. 

Ersetzt man die Isocyanide durch die entsprechenden Carbonsaure-ester-imide (X = OR), Thio-carbonsaure-S-ester-imide (X = SR) oder Carbonsaure-chlorid-imide (X = Cl), so konnen auch 2-substituierte Imidazole hergestellt werden296 ... 

Ref 2,4). More recently, ethylene diamine was reacted with 2-methyI-l-nitro-2-thio-pseudourea (also a prepn for ethylenegnani-dine without the nitro)(Ref 8). Treatment with sulfuric or perchloric acids converts this compound to the nitric acid salt of 2- amino-imidazole, mp 112-13°(Ref 7)... 

Reactions of 5f/-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-one 71, prepared by reaction of 1,2-diaminobenz-imidazole 72 with acetoacetic ester 73, with different reagents was described, in the search of new heterocycles with biological activity <2002CHE598>. When lactam 71 was treated with aromatic aldehydes in boiling 1-BuOH with addition of piperidine 74, 577-3-arylidene-2-methyl-l,2,4-triazepino[2,3- ]benzimidazol-4-ones 75a-c were obtained (Scheme 7). Coupling lactam 71 with phenyldiazonium chloride 76 in dioxane afforded the 3-phenylazo-substituted tricycle 77. When 71 was treated with phosphorus pentasulfide 78 in boiling dioxane or pyridine, its thio analog 79 was obtained. The reaction proceeded most efficiently when lactam 71 was refluxed with twofold excess of 78 in dry dioxane. These thiones 79 react with ammonia and amines by nucleophilic substitution. When 79 was refluxed with ammonia, benzylamine, piperidine, or morpholine, the 4-amino-substituted tricycles 80a-d were obtained. All the described compounds were identified by NMR, mass spectrometry, and IR spectroscopy. 

Only very few among the common amino acids possess a pK within the range 5.8-7.0. Therefore, the imidazole ring of histidine was suspected very early to represent the group responsible for nucleophilic attack on the substrate (38). The pK of free imidazol is 6.9 (39) that of imidazol, contained in histidine or its peptides, varies between 5.6 and 7.1 (40). Imidazol is well known to form unstable acyl derivatives, which undergo spontaneous hydrolysis because of the presence of the resonating triad unit —-N—C= N— (41). In addition, imidazol and its derivatives catalyze the hydrolysis of certain esters, especially those derived from phenols (42). Likewise, the behavior of imidazol towards thio esters reflects exactly the specificity of ChE s (see IV, 4). Thus, thiol esters are split (43), whereas thiono esters are resistant (21). 

The separation of cimetidine and its metabolites is usually carried out by extraction of the biological medium with 1-octanol fran an aqueous alkaline pH solution followed by mixing, addition of an internal standard and centrifugation. The extraction with octanol is repeated and the combined extracts are re-extracted with dilute hydrochloric acid. The aqueous acid solution is then separated, ethanol is added and mixed. This is then followed by saturating the mixture with a large amount of potassium or sodium carbonate to "salt out" the ethanol layer which contains the cimetidine and its metabolite, the sulfoxide. Several different internal standards have been used Metiamide, 1-methyl-3-[2-[[(5-methyl-imidazole-4-yl) -methyl] thio]ethyl]-2-thiourea,19 31 39 (N-cyano-N1-methy1-N"-(3-(4-imidazolyl)-propyl)guanidine32, and 13-hydroxy-theophylline. 0 After extraction the samples are either evaporated to dryness and reconstituted with a known amount of ethanol, injected directly or dissolved in the mobile phase for the HPLC analysis. 

Chemical Name Benzenamine, 4-(((2-(2-(4-chlorophenyl)ethyl)-2-(lH-imidazol-l-ylmethyl)-l,3-dioxolan-4-yl)methyl)thio)-, (2S,4S)-, hydrochloride... 

Chemical Name lH-Imidazole, l-(4-(4-chlorophenyl)-2-((2,6-dichlorophenyl)thio)butyl)-, mononitrate... 

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