Inhibitors of blood platelet aggregation. Effects of some 1,2-benzisothiazol-3-ones on platelet responsiveness to adenosine diphosphate and collagen

Abstract

A series of substituted 1,2-benzisothiazol-3-ones was synthesized, and the compounds were tested for ability to inhibit platelet aggregation induced by adenosine diphosphate and collagen in rats and guinea pigs ex vivo. Alkyl substituents at the 2-position bearing a basic group were necessary for ex vivo activity. Several of the compounds were potent inhibitors of adenosine diphosphate induced first-phase aggregation, but adverse toxicological findings terminated their further development. Preliminary studies suggested that inhibition of aggregation was not attributable to inhibition of prostanoid synthesis or to raised levels of cyclic 3',5'-adenosine monophosphate.

Crucial Role of Selenium in the Virucidal Activity of Benzisoselenazol-3(2H)-ones and Related Diselenides

“…For the synthesis of N -substituted benzisothiazol-3(2 H )-ones 2 the analogous reaction of 2-(chlorosulfanyl)benzoyl chloride ( 12 ) , obtained in a two-step synthesis starting from 2,2’-dithiodibenzoic acid ( 14 ) [ 11 ], with corresponding primary amines has been adapted. This reaction has already been successfully used with some primary amines [ 12 ], hydrazine derivatives [ 13 ] and amino acids [ 14 , 15 ] as reactants. Our further studies have demonstrated that the reactions of chloride 12 with other N -nucleophiles, e.g., thiourea, thioacetamide, acetamide and p-methylbenzenesulfonamide also resulted in N -substituted benzisothiazol-3(2 H )-ones, while reactions with CH -acids gave corresponding benzo[ b ]thiophen-3(2 H )-ones or/and 3-hydroxybenzo[ b ]thiophenes [ 16 ].…”

Benzisothiazolones arrest the cell cycle at the G2/M phase and induce apoptosis in HeLa cells

“…1 Among these, isothiazolones and benzisothiazolones (BIT) constitute an important class due to the presence of electrophilic sulfur as part of the ring. 2,3 The capability of these compounds to form disulde bonds with sulfur nucleophiles or to chelate biologically relevant metals such as zinc 4,5 has been correlated with their activities against human leukocyte elastase, [6][7][8][9] RNA polymerase, proteases, 10,11 HIV-NcP-7, 12 telomerase, 13,14 blood platelet aggregation, 15 microbes, [16][17][18] and proliferation. 19,20 Recently, Groutas and co-workers have evaluated the activities of benzisothiazolone derivatives against fungal strains, 21 and viruses causing Dengue and West Nile fever.…”

Iron‐Catalyzed One‐Step Synthesis of Isothiazolone/1,2‐Selenazolone Derivatives via [3+1+1] Annulation of Cyclopropenones, Anilines, and Elemental Chalcogens

“…Over the past few decades, isothiazolone derivatives have played an essential role in biology and medicine by virtue of their antibacterial, [1] antipsychotic, [2] antiviral, [3] antithrombotic, [4] and analgesic activities [5] . For instance, 1,2‐benzisothiazol‐3(2 H )‐one derivatives, [6a] substituted N ‐phenylisothiazolones, [6b] 2‐[3‐(trifluoromethyl)‐phenyl]isothiazolinone, [6c] and 2,5‐diarylisothiazolones [6d] have been reported as inhibitors of fungus, histone acetyl transferase, telomerase, and cartilage destruction, respectively (Figure 1).…”