Imidazo diazepine

Figure 7.28 Biosynthetic pathway of 2 -deoxycoformycin and coformycin biosynthesis of the imidazo-diazepine nucleus.

Most 1,3-diazepine syntheses employ the insertion of a single carbon fragment between the two nitrogen atoms. This is further exemplified by the use of tosyl isocyanate and methyl isothiocyanate in the preparation of the bicyclic imidazo[4,5-e][l,3]diazepines 46 and the imidazo[4,5-rf][l,3]diazepines 47 respectively <96JHC855, 96JCS(P1)2257>. 

Sequential condensations with 2-bromo-2-bromomethylcyclopropane-l-carboxylate and an imidazole derivative, and then guanidine gave the novel ring-expanded 108 with a 6H-imidazo[4,5-e][l,3]diazepine-4,8-dione skeleton <00JHC951>. Another 6-amino-2-phenyl derivative of this ring system has also been reported . 

JMC3596>, an imidazo[4,5-d][l,3]diazepin-8-ol as an AMP deaminase inhibitor <00JMC1508>, the antimaiarial mode of action of artemisinin <00FEBSL238>, and finally dithiepin-l,l,4,4-tetroxides as non-peptidic human galanin receptor antagonists <00BMC1383>. 

Amino methyl substituted pyrrolo-benzodiazepine 215 forms a cyclic aminal with aldehydes that can be further oxidized with Mn02 to fused 3-substituted imidazole 216. Alternatively, cyclic imine 217 can be submitted to TosMlC cycli-zation to afford unsubstituted 9H-benzo[e]imidazo[5,l-c]pyrrolo[l,2-fl][l,4]-diazepine 218 (Scheme 45, Section 3.1.1.2 (1993JHC749)). 

The pKa value for 2,3,6,7,8,9-hexahydro-4//-pyrimido[l,2-a]pyrimidine has been determined to be 11.22 using potentiometric titration methods. This value is nearly identical for the pKa values reported for the corresponding imidazo[l,2-a]pyrimidine and imidazo-[ 1,2-a ][ 1,3]diazepine heterocycles (62CJC1160). 

Amino-l-methylimidazole (169) reacted with DMAD145 in dioxane to form 30% of imidazo[l,2-a]pyrimidone (170), identified by the low-field 3-proton, and 5% of the diazepine 171, which was presumably built up by cyclobutene formation across the 4,5-double bond of 169 and ring expansion.148 Both l-methyl-2-methylthioimidazoline and its... 

The imidazo[4,5-J][l, 2]diazepine diribonucleoside (585) upon treatment with methanolic ammonia at room temperature undergoes a base-catalyzed ring contraction of the diazepine ring to give 4-amino-1,3-dihydro-l,3-bis(/ -D-ribofuranosyl)imidazo[4,5-c]pyridin-2-one (586) (58%) (Scheme 74) <86Ti5ii>. 

Examples of seven-membered heterocycles with significant antiviral activity include imidazo[4,5-e][l,3]diazepine-4,8-diones with anti-hepatitis C virus (HCV) activity <07BMCL2225> <07BMC4933> and benzo(indolo)fused 1,4-oxazepine derivatives as HCV RNA polymerase inhibitors that show excellent replicon potency <07BMCL3181>. Novel 2-chloro-8-[(arylthio)methyl]dipyridodiazepinone derivatives show activity against HIV-1... 

Without doubt, the most useful pyrazole synthons for building fused heterocyclic systems are aminopyrazoles. For instance, l-methyl-4-cyano-5-aminopyrazole is the starting material for the synthesis of pyrazolo [4,3-/]pyrrolo[l,2-a][l,4]diazepines which possess anxiolytic activity <94EJM233) l-phenyl-3-methyl-4-nitroso-5-aminopyrazole has been used to prepare imidazo[4,5-... 

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