Pharmacologically Active Carbazoles

N-Alkylamino carbazoles (e.g., 494 and 495) possess significant anti-convulsant and diuretic activity. Introduction of an aminopropyl chain at the N-atom seems to enhance the anti-convulsant activity in combination with methoxy groups at positions 2, 3, and 4, or a chlorine atom at the C-2 and C-3 positions (458). 

Rimcazole (BW 234U) (496) is a novel anti-pyretic, neuroleptic agent. It was found to be a specific competitive antagonist of a-sites in the brain. It reverses psychotic conditions induced in humans by phencyclidine and/or a-opiod antagonists, probably by binding to receptors in the brain (459-461). Rimcazole has an indirect effect on dopamine neurons with relative selectivity for AlO dopamine cells (462). 

Recently, some N-substituted carbazolyloxyacetic acid derivatives were investigated for the inhibition and modulation of Alzheimer s disease (AD) associated y-secretase, and it was found that selective reduction of AP42 and an increase of the less aggregatory Apsg fragment occurred (478). 

Various 9-A),]V-diethylaminopropyl-l,2,3,4-tetrahydrocarbazoles have been tested against Chagas disease (American trypanosomiasis), a human tropical parasitic disease. It was found that 8-chloro- and/or 8-methoxy-substituted analogs may have promise as trypanocidal substances (479). 

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Several biologically and pharmacologically active compounds have been prepared from the condensation of the acid chloride of 1-naphthoxyacetic acid with carbazole, iadole, or pyrrole ia 2A[ NaOH solution ia ethanol (63). Also, naphthyloxy derivatives of imidazole, benzimidazole, and benzotriazoles have been synthesized and screened for their antimicrobial, analgesic, and antiinflammatory activities. 2-Naphthyloxy derivatives are comparatively more active than 1-naphthyloxy derivatives (64). 

Vinylindoles have been studied extensively and used in the synthesis of carbazoles, alkaloids and other classes of pharmacologically active compounds. MMX force field calculations have shown that coplanar s-cis and. s-trans conformations of 3-vinylindole (84, Figure 2.11) are the most stable conformers they exhibit only slight differences in their thermodynamic stabilities [86]. 

Previously in this series, Kapil (1) and Chakraborty (3) described some of the biological properties of carbazole alkaloids. Since then, a great interest in this area has developed, as attested by some special reviews (7,8,190,192,194,195,255,256,259,260,395-397). In this section, we have summarized some of the important biological and pharmacological activities of this class of alkaloids. 

A huge number of synthetic or semisynthetic pyrrole, indole, and carbazole compounds with significant biological or pharmacological activities have been described. Therefore present coverage is restricted to those instances which appear to be of interest as candidate drugs. 

A broad structural variety of carbazole alkaloids vdth useful biological activities has been isolated from different natural sources. The pharmacological potential of this class of natural products led to the development of diverse methods for the synthesis of carbazoies [29,30]. We elaborated an efficient iron-mediated construction of the carbazole framework by consecutive C-C and C-N bond formation. This method provides highly convergent routes to carbazoies as demonstrated first for 4-deoxycarbazomycin B (Scheme 15.8) [31]. 

Because of their promising pharmacological properties, the carbazole-l,4-quinone alkaloids became attractive synthetic targets [30,63]. Murrayaquinone A has been isolated from the root bark of the Chinese medicinal plant Murraya euchrestifilia and shows cardiotonic activity [64], The koeniginequinones A and B have been obtained from the... 

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