Aromatic and Azaaromatic Diselenides, Benzisoselenazolones and Related Compounds as Immunomodulators Active in Humans: Synthesis and Properties

Abstract

Convenient syntheses of aryl diselenides 2, 1,2‐benzisoselenazol‐3(2H)‐ones 4 and their 1‐oxides 7 are reported. Reductive conversions of these compounds to bis(2‐carbamoyl)‐phenyl diselenides 5 and oxidative cyclization of 5 to 1,2‐benzisoselenazol‐3(2H)‐one 1‐oxides 7 as the methods for the synthesis of these compounds are reported. Their ability to induce cytokines, such as TNF and IFN‐γ, in human peripheral blood leucocyte cultures is described.

New Organoselenium Compounds Active against Pathogenic Bacteria, Fungi and Viruses

“…Ebselen (1a) and unsubstituted benzisoselenazol-3(2H)-one (1b) were prepared by the treatment of 2-chloroselenobenzoyl chloride (10) with aqueous ammonia or aniline, respectively, the same way as reported in our previous works. 7) Chloride 10 was obtained in a four-step synthesis starting from anthranilic acid.…”

“…Compounds 1a (88% yield, mp 181-182°C), 7) 1b (86% yield, mp 231-232°C), 7) 2a (84% yield, mp 156-158°C), 7) 2b (68% yield, mp 98-99°C), 12) 2d (83% yield, mp 99-101°C), 13) 2e (55% yield, mp 90-91°C), 14) 2f (94% yield, mp 151°C), 7) 2g (96% yield, mp 148-151°C), 13) 2i (96% yield, mp 80-82°C), 7) 2j (95% yield, mp 87-89°C), 7) 3b (85% yield, mp 148-150°C), 15) 4a (85% yield, mp 185-187°C) 7) have been known and are reported in references cited. Adamantyl)benzisoselenazol-3(2H)-one (2h) 75% yield, Reaction of Benzisoselenazol-3(2H)-one (1b) with Formaldehyde Benzisoselenazol-3(2H)-one (1b) (0.39 g; 2 mmol) and 38% aqueous solution of formaldehyde in excess (1.5 ml) were placed in a hermetically closed test-tube.…”

“…[4][5][6] In our previous papers we reported that various 2-substituted benzisoselenazol-3(2H)-ones and related diaryl diselenides exhibited high activity as immunostimulants inducing cytokines such as interferon, tumor necrosis factor and interleukin (IL-2) in human peripheral blood leukocytes. 7,8) Moreover, some of these compounds, particularly their 7-azaanalogues, exhibited high inhibitory activity against pathogenic bacteria, fungi and viruses. 9) In this paper we report synthesis, chemical properties as well as inhibitory activity against viruses, bacteria and fungi of ebselen analogues (2-6), having in 2-position alkyl groups (2) or containing oxaalkyl or azaalkyl functions (3)(4)(5)(6).…”

Water-dependent synthesis of biologically active diaryl diselenides

“…Direct reduction of benzisoselenazolones with different reducing agents -sodium borohydride, hydrazine, ascorbate or phosphoric acid (h), [33][34][35][36] nucleophilic substitution of o-iodobenzamides with lithium diselenide (i), 37 under radical conditions from the reaction of 2-benzylselenobenzamides with triphenyltin hydride and further treatment with benzoyl peroxide (j) 38 and few protocols starting from 2,2-diselenobis(benzoic acid) -through the formation of the corresponding dichloride and further reaction with amine (k) 39 or by EDC (l) 40 and DCCmediated (m) 41 coupling reactions (Scheme 2).…”

Diaryl diselenides and benzisoselenazol-3(2H)-ones as oxygen-transfer agents

“…The method has a general value, competitive formation of selenides is avoided, yields of diselenides are high, also PPDS and PADS (24) were obtained in this manner. 16,24,47,48 The synthesis of diselenide 24 from 9,10-dibromoanthracene (83) presented in Scheme 20 is an example. A more general method for the synthesis of ebselen and other 2-substituted benzisoselenazol-3(2H)-ones (90) as well as for synthesis of 2-carbamoylphenyl diselenides (83), presented in Scheme 21, was elaborated in our laboratory as a modification of the old procedure reported by Lesser and Weiss.…”