Tetrazoles biologically active

In general 1,5-dialkyltetrazoles, in which the A(l)-substituent has four to six carbons, show activity on the central nervous system. When the 1- and 5-positions are bridged by a methylene chain, the activity is maximized. Pentamethylene tetrazole (244), which is probably the most important biologically active tetrazole, is a standard drug in this area... 

Biologically Active Tetrazoles (—CN4H versus—C02H) 355... 

Structures have been determined for a large number of 1-substituted tetrazoles. The number of studies dedicated to this type of compounds is larger than the overall number of all other publications. The great interest in 1-substituted 31 and 1,5-disubstituted tetrazoles 5 is mostly due to the biological activity of this type of compounds the 1,5-disubstituted tetrazole fragment is an isosteric analog of ester and m-amide groups. 

Esters of tetrazole-5-carboxylic acids are attractive substrates for aminolysis with various amines. These reactions are frequently involved in the synthesis of complex biologically active substances containing a tetrazole ring (cf. Section 6.07.12.1). Reactions of ethyl tetrazole-5-carboxylate 369 with anilines may be cited as an example that results in products of type 370 (Equation 68) <2003BML369>. 

Butler listed over 20 kinds of biological activity of tetrazoles <1996CHEC-II(4)621>. Within the last decade, the number of publications concerning application of tetrazoles in pharmaceuticals and investigations of their biological activity has grown steadily and reached several hundreds (with the exception of patents). It is impossible to discuss all... 

Below are tetrazole derivatives exemplifying pharmaceutical substances not only endowed with biological activity (cf. Section 6.07.12.1.1), but also holding a firm place in the contemporary drug market . 

The use of a high-loaded polystyrene (HLP) support has been described for the large scale synthesis of RNA. Biologically active ribozyme sequences were synthesised on a 200 pmol scale using this support in conjunction with 2 -0-tert-butyldimethylsilyl monomers and 5-ethylthio-l/f-tetrazole as the activating agent. 

Many tetrazoles are biologically active. 1,5-Pentamethylenetetrazole 10 (pentetrazol, Cardiazol) is the most widely known of such compounds. It is a CNS-active cardiac and respiratory stimulant and narcotic antagonist and is injected in cases of barbiturate poisoning. It is prepared via hexano-6-lactam by addition of sodium azide and sulfuric acid to cyclohexanone (Schmidt reaction) ... 

For every biologically active carboxylic acid, there is a bioisosteric compound in which the carboxyl group is replaced by a tetrazol-5-yl moiety. The tetrazole compounds are degraded biologically more slowly than carboxylic acids. For instance, the tetrazole analogue 11 of nicotinic acid reduces the fatty acid and cholesterol levels in blood. 

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