Activity antiinflammatory

The most studied properties of 2-aminothiazoles and 2-imino-4-thiazolines are related to their antiinflammatory activity (Table VI-9). Two classes of compounds have even been given trade names Sudoxicam (418) and Niridazole. also named Ambilhar (419) (Scheme 238). 

The thiazolecarboxylic acids and especially 2-alkyl-5-thiazolecarboxylic acids have hypolimic vasodilatory and antiinflammatory activity (19, 59, 60). 

Ketopregnan-21-oic Acids, the 17(3-Carboxy Androstanes, and the D-Homocorticoids. In the course of studies on the metabohsm of fluocoitolone (103) the formation of the water-soluble carboxyhc acid (105, R = H) was reported. As a free 21-hydroxyl is not necessary for antiinflammatory activity, it was concluded that the esters (105, R = alkyl) of the preceding metabohte would possess antiinflammatory activity on topical administration but would be devoid of systemic activity when hydrolysis to the free acid occurs followed by... 

In 1973 D-homo corticosteroids (109—112), eg, D-homo-9a- uoroprednisolone acetate (111) were reported to have antiinflammatory activity (107). Compounds such as 21-acetoxy-liP- uoto-9a-chloto-17aa-hydtoxy-D-homo-ptegn-4-en-3,20-dione (110) had especially strong topical activity with weak systemic activity (108). Other preparations of D-homocorticoids included... 

Several biologically and pharmacologically active compounds have been prepared from the condensation of the acid chloride of 1-naphthoxyacetic acid with carbazole, iadole, or pyrrole ia 2A[ NaOH solution ia ethanol (63). Also, naphthyloxy derivatives of imidazole, benzimidazole, and benzotriazoles have been synthesized and screened for their antimicrobial, analgesic, and antiinflammatory activities. 2-Naphthyloxy derivatives are comparatively more active than 1-naphthyloxy derivatives (64). 

Derivatives of ubiquiaones are antioxidants for foodstuffs and vitamins (qv) (217,218). Ubichromenol phosphates show antiinflammatory activity (219). Chroman o1 compounds inhibit oxidation of fats and can be used ia treatment of macrocytic anemias (220). Monosulfate salts of 2,3-dimethoxy-5-methyl-6-substitutedhydroquiaone have been reported to be inhibitors of Hpid oxidation ia rats (221). Polymers based on chloranilic and bromanilic acid have been prepared and contain oxygenated quiaones (63), which are derived from 1,2,3,4-benzenetetrol (222). 

Eupatin (69, R = H) and Eupatoretin (69, R = CH3), which are isolated from thistle perennials, show moderate cytotoxicity against human carcinoma of the nasopharynx (236). Baicaleia (70) salts exhibit antiallergic and antiinflammatory activity. 3,4,5-Trimethoxyphenoxyacetamides are hypotensives and diuretics and are useful for controlling arrhythmia duting anesthesia (237). 

Glutathione peroxidase [9013-66-5] oxidizes glutathione, and helps to remove inorganic and organic hydroperoxides (221] It exhibits antiinflammatory activity in experimental uveitis of rats (234). 

Recently, Picciola et al. (81FES1037) prepared some 2iT-indazole derivatives containing a phenylalkanoic acid residue with potential antiinflammatory activity (693). M.G. 18755 (R = CHMeC02H, R = R = R = H) and its lysine salt, M.G. 18334, showed greater activity than ibuprofen, and the homologous butyric acid derivative M.G. 18860 showed good activity as a platelet aggregation inhibitor. 

Trihydroxy-6,16a-dimethyl-2 -phenyl-2 H-pregna-2,4,6-trieno[3,2-c] -pyrazol-20-one-21-acetate, commonly named cortivazol (696), has been used since 1962 by Merck Co. as a glucocorticoid (B-76MI40404). Tricyclic pyrazoles (697) have been found to possess antiarrhythmic and antiinflammatory activities (76JHC545). 

In the search for new structures with antiinflammatory activities some 1-substituted 3-dimethylaminoalkoxy-lJ/-indazoles (704) have been synthesized and pharmacologically tested (66JMC38). Doses of 20-40 mg g i.p. produced sedation, muscle relaxation and motor incoordination, whereas doses of 80-100 mg kg produced depression. Toxicity was fairly constant in all series, varying from 120 to 150 mg kg i.p., with the exception of compounds possessing a nitro group or an amino group in the indazole nucleus, which provoked cyanosis. 

With Af-acyl or Af-sulfonyl hydrazines as nucleophiles, Zincke salts serve as sources of iminopyridinium ylides and ylide precursors.Reaction of the nicotinamide-derived Zincke salt 8 with ethyl hydrazino urethane 42 provided salt 43, while the tosyl hydrazine gave ylide 44 (Scheme 8.4.14). ° Benzoyl hydrazines have also been used in reactions with Zincke salts under similar conditions.Af-amino-1,2,3,6-tetrahydropyridine derivatives such as 47 (Scheme 8.4.15), which showed antiinflammatory activity, are also accessible via this route, with borohydride reduction of the initially formed ylide 46. ... 

Further oxidation of the carbon at position 21 is interestingly consistent with antiinflammatory activity. Thus oxidation of flucinolone with copper (II) acetate... 

Halogenation of the 7 position also proves compatible with good antiinflammatory activity. Construction of this compound, aclomethasone dipropionate (80), starts by introduction of the required unsaturation at the 6,7 position by dehydrogenation with DDQ (76). The highly hindered nature of the hydroxyl at position 17 requires that a roundabout scheme be used for formation of the corresponding ester. Thus treatment of 76 with ethyl orthoformate affords first the cyclic orthoformate This then rearranges to the 17 ester on exposure to acetic acid. Acylation of the 21 alcohol is accomplished in straightforward fashion with... 

A biarylpropionic acid derivative containing a furan ring as a prominent feature has antiinflammatory activity. The patented synthesis involves a straightforward organometal1ic addition of ethyl lithioacetate to aldehyde 12 followed by saponification... 

Replacement of chlorine on the pendant benzoyl group by azide is apparently consistent with antiinflammatory activity. Acylation of indomethacin intermediate with p-nitrobenzoyl chloride leads to the corresponding amide (7). Saponification ( ) followed by reduction of the nitro group gives the amine 9. The diazonium salt (10) obtained on treatment with nitrous acid is then reacted with sodium azide there is thus obtained zidomethacin (11). 

A seemingly complex heterocycle which on close examination is in fact a latentiated derivative of a salicylic acid shows antiinflammatory activity. It might be speculated that this compound could quite easily undergo metabolic transformation to a salicylate and that this product is in fact the active drug. Condensation of acid 134 with hydroxyl amine leads to the hydroxamic acid 135. Reaction of... 

Flufenamic acid (162) is a reasonably well-established NSAID (Non Steroidal Anti Inflammatory Drug). Alkylation of its potassiuni salt with the hydroxyethyl ethyl ether of ethylenechlo-rohydrin affords the latendated derivative etofenamate (163) [41]. Antiinflammatory activity is apparently retained when both rings in the fenamate series carry carboxyl groups. Thus, condensation of dichlorobenzoic acid 164 with anthranilic acid (165) by means of nucleophilic aromatic... 

Replacement of one of the benzene rings in a fenamic acid by pyridine interestingly leads to a compound which exhibits antiliypertensive rather than antiinflammatory activity. Preparation of this agent starts with nucleophilic aroniatic substitution of anthranilic acid (8) on 4-chloropyri-dine. The product (9) is converted to its acid chloride (10), and this is condensed with piperidine. There is thus obtained ofornine (11) f31. 

REGAL J F, FRASER D G, WEEKS c E, GREENBERG N A (2000) Dietary ph)doestrogens have antiinflammatory activity in a guinea pig model of asthma. Proc Soc Exp Biol Med. 223 372-8. 

Although the absolute configurations of the products are opposite to that of antiinflammatory active compounds, and the substrate specificity is rather restricted as to the steric bulkiness around the reaction center, the enzyme system of A. bronchisepticus was proved to have a unique reactivity. Thus, detailed studies on the isolated enzyme were expected to elucidate some new interesting mechanism of the new type of decarboxylation. Thus, the enzyme was purified. (The enzyme is now registered as EC 4.1.1.76.) The molecular mass was about 24kDa. The enzyme was named as arylmalonate decarboxylase (AMDase), as the rate of the decarboxylation of phenylmalonic acid was faster than that of the a-methyl derivative. ... 

Abstract Seventy three coumarinc derivatives were synthesized. The structures of these obtained products were proved on the basis of spectral and analytical data. A comparative pharmacological study showed that these compounds have different anticoagulant and antiinflammatory activities. The most prospective compounds are with enhance activity. 

It can be seen that though the aldehydic function is important for antiinflammatory activity as observed in compoimd 36, its conversion to the unsaturated cyanoesters 37 shows an increase in the activity. Similarly, the ethers 39 with the ortho aldehydic group upon conversion to benzofurans 6 show a sHght increase in activity. None of the compounds tested showed any analgesic activity. 

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