Diaziridines

Diaziridines are colorless powders, oils or liquids. It is sparingly soluble in water, good in organic solvents. The most studied representative of the class is N, N'-ethylene-bis- (3,3-dimethyldiaziridine). It is a white crystalline powder with a yellowish tinge, easily soluble in water, in 95% alcohol, chloroform. Melting point 113-118 C.

Diaziridines that do not contain substituents on the nitrogen atoms of the cycle, including the spirostructures, can be synthesized by one of the following methods:

1. The interaction of ketones with ammonia and hydroxylamine-O-sulfonic acid (HASA) in water-methanol medium at a low temperature (-30 C), followed by heating to 20 C ^[1] .
   
2. The interaction of ketones, ammonia and monochloramine. The optimal conditions are the chlorination of a solution of liquid ammonia in methanol by the action of ButOCl at low temperature, followed by mixing with liquid ketone ^[2] .
   
3. Through the preliminary preparation of hydroxylamine-O-sulfonic acids or their esters, which are further treated with a stream of ammonia gas in water or in methanol ^[3] .
   

The synthesis of N-substituted diaziridines is described in detail in a number of references ^{[4] [5] [6] [7]} .

Activity

According to preliminary studies, 100% of the studied molecules of diaziridines have a pronounced neurotropic activity (antidepressant, tranquilizing, neuroleptic, or their combination). Some molecules surpass such “reference drugs” as fluoxetine , amitriptyline , nialamide , imipramine, and others in their degree of effect, time of onset of action, and are much less toxic.
The spectrum of the psychotropic action of N, N'-ethylene-bis- (3,3-dimethyldiaziridine) and some other members of the diaziridine class was identified using models of psychopathological states in animals. ^[8] The presence and peculiarities of the antidepressive effect of the studied compounds are evidenced by the results of the assessment of their activity on the “learned helplessness” behavior depression model. The behavior of the stressed N, N'-ethylene-bis- (3,3-dimethyldiaziridine) injected mice began to normalize after two days of administration. At the same time, under similar conditions, pyrazidol reduced the latent period of avoidance only on the sixth day, and the effect of melipramine was manifested on the twelfth day.

Toxicity

Diaziridines are low toxic . The introduction of N, N'-ethylene-bis- (3,3-dimethyldiaziridine) in the dosage form for six months rats and dogs does not cause violations of the general condition, the dynamics of body weight, hematological and biochemical parameters, the functional activity of the liver and kidneys, the histological structure of the internal bodies ^[9] .

Mechanism of Action

The mechanism of action of diaziridines is not well understood. It is known that diaziridines exhibiting an antidepressant and tranquilizing effect are partial positive modulators of mGluR1, selective mGluR2 antagonists, partial antagonists of mGluR8, and 5-HT3 inhibitors. Diaziridines exhibiting neuroleptic action are partial positive modulators of mGluR1 and mGluR2, selective mGluR3 antagonists, partial mGluR8 antagonists.

• Metabotropic glutamate receptors
• Depression
• Schizophrenia
• Anxiety disorder

• pharmdiscovery.com