Benzodiazepine derivates, ring structure

Benzodiazepine derivates, seven-membered rings with 2 N atoms in 1,4 position are the pivotal structures of the benzodiazepine class of breakthrough CNS (central nervous system) drugs such as Librium and Valium. The most recent drug in this class, Sepracor s Lunesta (eszopiclone), is composed almost entirely of A-heterocyclics. Like most modern drugs, esczopi-clone also has a chiral center ... 

The same approach was readily adaptable to solid-phase synthesis. A small library of unnatural derivatives of 140 was prepared with variation of the configuration and nature of R1 and R4 and with substitution on the benzene ring <2000JC0186>. Three natural alkaloids, Verrucine A, B, and Anacine, were synthesized by a similar pathway and the pyrazino[2,l- ]quinazoline as opposed to the benzodiazepine structure of Anacine was proved <2001JNP1497>. Fiscalin B and other derivatives were prepared by solid-phase synthesis using polyethylene glycol (PEG) resin <2002USP6376667>. 

Dehydroquinic acid, shikimic acid, and chorismic acid are carboxylated compounds containing a six-membered carbocyclic ring with one or two double bonds (Fig. 143). The secondary products derived from these substances either still contain the ring and the C -side chain of the acids (see the structure of the benzoic acid derivatives, of anthranilic and 3-hydroxyanthranilic esters, D 8, D 8.2, D 8.4 and D 8.4.1) or have additional rings (see the formulae of naphthoquinones and anthraquinones, D 8.1, of quinoline, acridine, and benzodiazepine alkaloids, D 8.3.2). The carbon skeletons may be substituted by isoprenoid side chains (see the structure of ubiquinones, D 8.3) and may carry different functional groups, e.g., hydroxy, carboxy, methoxy, and amino groups. 

Kaur et al. (2012) carried out microwave-assisted synthesis of 2-hetryl amino substituted novel analogs of l,4-benzodiazepine-5-piperidinyl carboxamides. The 2-iminothioethyl ether derivatives undergo smooth nucleophilic displacement reaction with variety of hetryl amines and afforded products in excellent yields (90%) in 2-6 min. under microwave irradiation. They have highlighted the importance of the incorporation of some pharmacophores such as 2-aminopyridinyl, pyrimidinyl, and benzothiazolyl in 1,4-benzodiazepine nucleus. The amide functionality (the CO-NH group) in the seven membered heterocyclic ring of 1,4-benzodiazepine nucleus is the only active functional group present in this molecule, which will provide an important site for the incorporation of a wide variety of heterocycles (and fused heterocycles) and heterocycle appended structures in this molecule. 

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