Salicylic Acid Analogues

Salicylic acid analogues are often active as nonsteroidal antiinflammatory agents because they interfere with biosynthesis of prostaglandins. Diflunisal (3) appears to be such an agent. It is synthesized from the nitrobiphenyl 1 by catalytic reduction to... 

Discuss Salicylic Acid Analogues as potent antipyretic analgesics. Give suitable examples of support yom answer. 

A good number of salicylic acid analogues have also been foimd to possess anti-inflammatory aetions, e.g., aspirin, salol, salsalate, sodium salicylate, salicylamide, benorilate, choline salicylate, flufenisal etc., in addition to their antipyretic analgesic property. These compounds have been individually treated in Chapter 9. 

Give a comprehensive accoimt of the following categories of drugs used profusely as NSAlD(s) (a) Salicylic acid analogues,... 

Good non-colored negative charging CCAs have been obtained by making non-colored analogues of the 2 1 chromium complex azo dyes. This is achieved by making the metal complex of an aromatic ortho-hydroxy carboxylic acid. Typical examples are the chromium, aluminum, and zinc complexes of di-tert-butyl salicylic acid, e.g., BONTRON E-8136 41 (53) and BON-acid36,41,42 e.g., BONTRON E-82 (54). 

In view of the well-known pharmacological action of aspirin, it was thought that the fluorine analogue, O (fluoroacetyl) salicylic acid, might be of considerable interest. The compound was readily made by acylation of salicylic acid by fluoroacetyl chloride in the presence of pyridine. The l.d. 50 for subcutaneous injection into mice was approximately 15 mg./kg. After injection the mice went into a drugged sleep, and died overnight. 

Complex formation of nickel(II) with a variety of hydroxy acids has been investigated. It has been reported that in aqueous solution in the pH range 6-7.2 at 25 °C, a 1 1 neutral complex is formed between nickel(II) and the salicylato monoanion, HOCsH Oj (Keq —1.4 x 10 6), or its 5-substituted analogue, with the further release of a proton.1789,1790 The effects of substituents on the stability constants of nickel complexes with various 4- and 5-substituted salicylic acids were also studied.1791,1792... 

SAM-dependent methylation of salicylic acid. The salicyl alcohol derivative salicin, found in many species of willow (Salix species Salicaceae), is not derived from salicylic acid, but probably via glucosylation of salicylaldehyde and then reduction of the carbonyl (Figure 4.27). Salicin is responsible for the analgesic and antipyretic effects of willow barks, widely used for centuries, and the template for synthesis of acetylsalicylic acid (aspirin) (Figure 4.27) as a more effective analogue. 

Hydroxybenzoic acid (salicylic acid) does form a complex, although its formation is not favored when compared to that of the picolinato ligand. Presumably this, at least to an extent, reflects the fact that the chelate formed with salicylate has a six-membered ring, and six-membered chelates are much less favored than the five-membered analogue. 

Dimroth P, Greull G, Seyfferet R, Lynen F (1972) Hoppe Syler s Z Physiol Chem 353 126 Dimroth P,Ringelmann E, Lynen F (1976) Eur J Biochem 68 591 Bhogal P, Shoolingin-Jordan P. Incorporation of novel substrates into 6-methylsalicylic acid and triacetic acid lactone analogues by 6-methyl salicylic acid synthase. In Polyketides chemistry, biochemistry, molecular genetics. 1996. Royal Society of Chemistry, Bristol, UK, p 19... 

Acnisal salicylic acid, aconiazide [inn] is an isoniazid analogue and an ANTITUBERCULAR and ANTIBACTERIAL AGENT, aconitine is an alkaloid from monk s hood or wolfsbane (Aconitum napellus) and other Aconltum spp. (Ranunculaceae). It is a NEUROTOXiN implicated in poisoning by A. spp., especially, 4. chasmanthum in India. Experimentally, it is a SODIUM-CHANNEL ACTIVATOR that binds to Na -channels, slows inactivation, shifts inactivation to a more negative value, and alters ion specificity. This results in repetitive firing of neurons, with marked effects on the heart including positive inotropism and arrhythmias. Aconitine (and the related alkaloid delphinine) were formerly used in... 

Similar results have come from studies of the DEBS 1-i-TE system in vitro [53]. When DEBS 1 -I- TE was incubated with appropriate precursors in the absence of the reducing agent NADPH the keto 27 and the pyrone 28 analogues of the triketide lactone were obtained (Scheme 13) [53,54]. This latter result resembles the similar formation of a pyrone product by the animal PAS and the 6-methyl-salicylic acid PKS under similar conditions [55]. Clearly, the /Tketoester intermediates can be transferred from one module to the next without further processing, even in modules which are geared to the production of a hydroxyester intermediate. 

The fact that the presence of the hydroxy function originating from the salicylic acid is an essential requirement for cestodicidal and flukicidal activity, led Hoechst scientists to prepare a variety of 2,6-dihydroxybenzoic acid anilides. The most effective compound of the series were 4 -chloro/bromo-6-hydroxysalicy-lanilides (5a,b). Of these, the bromo analogue, called resorantel (terenol, 5b) was found to be more effective than the 4 -chloro analogue (5a) [12]. Resorantel was later... 

A variety of topical (most commonly salicylic acid, corticosteroids, anthralin, and/or vitamin D analogues)... 

Kwon, Y., Theoretical study on salicylic acid and its analogues intramolecular hydrogen bonding, J. Mol. Struct. Theochem, 532, HI-Til (2000). 

These compounds, derived from anthranilic acid XXXVII, R = H), can be considered as analogues of salicylic acid. Three active anti-inflammatory... 

Attempted formation of the acid chloride of (121) led instead to (110 R = Me, = Pr ) in 50% yield (Equation (38)), suggesting a potential rational synthetic route to unsymmetrical disalicylide derivatives <87T1519>. Other routes for the preparation of such diones, such as the pyrolysis of acetylsalicylic acid oligomers used for the preparation of disalicylide itself <82Mi 924-02) and the dimerization of salicylic acid derivatives <88CZ125, 9iJOC4525>, presumably would at best yield mixtures if applied to unsymmetrical analogues. 

The first PC compound was prepared using the 2-methanesulfonylpyrimidine (OMSP) 6 and the salicylic acid ester in DMF. The sulfonyl compound 6 was a very efficient intermediate to synthesize 2-substituted pyrimidines [8]. The meth-anesulfonyl group in 6 is easily replaced by nucleophilic reagents like 7 and 8 (Fig. 2.5.5) [7, 9, 10]. This method was generally employed to synthesize numerous analogues aiming at new herbicides, not only with a high potency but also with an enhanced crop safety. Structural modifications were first made with the skeletal structure 9 (Fig. 2.5.6) [3]. 

Zwanenburg B, Mwakaboko AS (2011) Strigolactone analogues and mimics derived Ifom phthalimide, saccharine, p-tolyhnalondialdehyde, henzoic and salicylic acid as scaffolds. Bioorg Med Chem 19 7394—7400. doi 10.1016/j.bmc.2011.10.057... 

A series of halogenated transformation products of pharmaceuticals and related environmental contaminants have been characterized by Larive et by the use of H and NMR including /hh couplings this included chloro- and bromoderivatives of salicylic acid and halogenated analogues of naproxen, gemfibrozil, diclofenac, tertiary octyl-phenol and bisphenol A. 

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