Probucol, structure

The phenothiazines, chlorpromazine and promethazine, have been described as inhibitors of CCU-induced lipid peroxidation at relatively high concentrations in rat liver microsomes (Slater, 1968). Structural modifications of chlorpromazine were undertaken to try to increase antioxidant activity and maintain molecular lipophilicity. The 2-N-N-dimethyl ethanamine methanesulphonate-substituted phenothiazine (3) was found to be a potent inhibitor of iron-dependent lipid peroxidation. It was also found to block Cu -catalysed oxidation of LDL more effectively than probucol and to protect primary cultures of rat hippocampal neurons against hydrogen peroxide-induced toxicity in vitro (Yu et al., 1992). 

Probucol (4,4/-[(l-methylethylidene)bis(thio)]-bis-[2,6-bis(l,l-dime-thylethyl)phenol]) is a cholesterol-lowering drug that has been reported to exist in two forms [27]. Form II has been found to exhibit a lower melting point onset relative to Form I, and samples of Form II spontaneously transform to Form I upon long-term storage. The structures of these two polymorphic forms have been reported, and a summary of the crystallographic data obtained in this work is provided in... 

Dimensional structures of small molecules that exhibit IL-1 modulating activities. They are tenidap, ciprofloxacin, 3-Deazaadenosine, (SK F 86002), E5110, DMARDs (Chloroquine, Auranofin, Sodium aurothiomalate and Dexamethasone) tiaprofenic acid, dexamethasone, tricyclic-ylidene-acetic acid and its derivative, Probucol, eicosapentenoic acid + docosahexenoic, pentoxifylline, Denbufylline, and Romazarit (Ro-31-3948). 

The discovery of the hypocholesterolaemic properties of probucol or DL-581 [4.4-(isopropylidene-dithio)bis(2.6-di-t-butyl-phenol)] led to a structure-activity study among related compounds75. The result of this study was the selection of DL... 

The conformations of the probucol molecule in the two forms were found to be quite different. In Form II, the CSCSC chain is extended, and the molecular symmetry approximates Cjv This molecular symmetry is lost in the structure of Form I, where now the torsional angles around the two CS bonds deviate significantly from 180°. Steric crowding of the phenolic groups by the t-butyl groups was evident from deviations from trigonal geometry at two phenolic carbons in both... 

Fig. 2 Crystal structures of Forms I and II of Probucol. (Adapted from Ref. f)...

Gerber, J.J. Caira, M.R. Letter, A.P. Structures of two conformational polymorphs of the cholesterol-lowering drug probucol. J. Cryst. Spect. Res. 1993, 23, 863-869. 

Selective COX-2 inhibitors Mass screening of the Parke-Davis library for compounds that would inhibit COX-2 identified original hits derived from 2,6-di-tert-butylphenol (generic structures I and II , Fig. 5.11). These compounds are related to probucol and are totally different from the previously reported selective COX-2 inhibitors. ... 

Fig. 3. a Molecular structure of probucol b stereoview of the crystal structure of Form I c stereoview of the crystal structure of Form II. (Adapted from [59] with permission)... 

Orf/ o-alkylsubstituted phenol 2,6-di-fert-butyl-4-methylphenol (butylated hydroxytoluene, BHT) and its structural analogues are efficient antioxidants. They are widely used for the stabilization of polymers and technical oils [1-16]. Being almost nontoxic, BHT is applied as antioxidant in food products. At the same time BHT and its structural analogues serve as an active basis for several widely used medicines of bioantioxidant nature, such as dibunolum and probucol [55], Molecular structures for some orf/zo-alkylsubstituted phenolic antioxidants are shown below ... 

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