Sulindac 42

Sulindac (Shen et al. 1971) is another NS AID and exists in two nonsolvated solid modifications. The chemical consistency of the two solid phases was demonstrated by various methods, including solution NMR. The two polymorphs were designated Forms I and n of sulindac. Differences in the solid state were detected by XRPD and DTA (Fig. 3-3). 

It is clear from the DTA curves that Form I is the more stable polymorph in the high-temperature range. However, based upon solubility and rate of dissolution measurements (Tables 3-2 and 3-3 and Fig. 3-4), the reverse situation applies at lower temperatures. Form II is more stable near room temperature. The extrapolation of the solubility and dissolution rate date indicate a transition point at about 165°C for Form II to Form I. This transition is not observed in the DTA curve for Form II, as it should be if the situation were thermodynamically ideal. The lack of transition in the DTA curve corresponds to a case of suspended transformation. Forms I and II of sulindac are enantiotropic polymorphs, with Form II being more stable at room temperature (McCauley 1991). 

Controlled crystallization from solutions of sulindac in the lower temperature region, below the transition temperature (actually, less than 100°C because no solvent crystallizations are performed at higher temperatures), ordinarily results in the formation of Form n of sulindac. 

Rapid crystallization in the lower temperature range tends to yield Form I of sulindac. The use of chlorinated solvents (methylene chloride, chloroform, 1,1-dichloroethane, etc.), either under carefully controlled conditions or more chaotic circumstances, results in the isolation of Form I of sulindac after drying off of the solvent. The initially isolated solid in these cases was determined to be a sulindac solvate of the corresponding chlorinated solvent. Once the solvates are broken by drying. Form I of sulindac results, indicating a strong structural relationship between Form I and the solvates. 

Chemical Name (Z)-5-fluoro-2-methyl-1 [ [4-(methylsulfinyl)phenyl] methylene] -IH-indene-3-acetic acid 

Trade Name Manufacturer Country Year Introduced 

6-Fluara-2-Methylindanane To 932 grams polyphosphoric acid at 70°C on the steam bath is added 93.2 grams (0.5 mol) p-fluoro-o-methylhydrocinnamic acid slowly with stirring. 

This temperature is gradually raised to 95°C and the mixture kept at this temperature for 1 hour. The mixture is allowed to cool and added to 2 liters of water. The aqueous layer is extracted with ether, the ether solution washed twice with saturated sodium chloride solution, 5% Na2C03 solution, water, and then dried. The ether filtrate is concentrated with 200 grams silica-gel, and added to a five pound silica-gel column packed with 5% ether-petroleum ether. The column is eluted with 5 to 10% ether-petroleum ether and followed by TLC to give 6-fluoro-2-methylindanone. 

5-Fluoro-2-Methyl-1-(p-Methyisuifinyibenzylidene)-3-lndeny acetic Acid To a solution of 3.4 grams (0.01 mol) 5-fluoro-2-methyl-1-(p-methylthiobenzylidene)-3-indenylacetic acid in a 250 ml mixture of methanol and 100 ml acetone is added a solution of 3.8 grams (0.018 mol) of sodium periodate in 50 ml water with stirring. 

5-Fluoro-2-Methylindene-3-Acetic Acid A mixture of 18.4 grams (0.112 mol) of 6-fluoro- 

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Analgesics. Four examples of antiinflammatory agents are Sulindac [38194-50-2] based on a monofluoro indene derivative diflunisal... 

Nonsteroidal Antiinflammatory Drugs. Nonsteroidal antiinflammatory dmgs (NSAIDs) include, among the numerous agents of this class, aspirin (acetylsaflcyhc acid), the arylacetic acids indomethacin and sulindac, and the arylpropionic acids, (5)-(147) and (R)-(148) ibuprofen, (5)-(149) and (R)- (150), flurbiprofen naproxen (41), and fenoprofen (see Analgesics, antipyretics, and antiinflammatory agents Salicylic acid and related compounds). 

Fluormated agents such as flurbiprofen (II), flunisal(i2), diflunisal (13), and sulindac (14), acting as prostaglandin synthesis mhibitors, have been available for some time [5] The recent introduction of flunoxaprafen (15), a lipoxygenase inhibitor, is notable It reportedly produces considerably less severe gastric disturbance [75]... 

Dimethyl tubocurarine Iodide Cyanacetamid Ethionamide Protionamide Cyanamide Albendazole Butalamine HCl Cimetide Cyanoacetamide Allopurinol Cyanoacetic acid Aminometradine Amisometradine Cyclopentamine HCl Sulindac... 

Ferroglycine sulfate Ferrous fumarate Fluoranthene Flora ntyrone Fluoroacetyl chloride Afloqualone p-Fluorobenzaldehyde Sulindac Fluorobenzene Flubendazole o-Fluorobenzoyl chloride Flunitrazepam... 

There are several hundred reported NF-kB inhibitors (see www.nf-kb.org for a complete and updated list). These inhibitors include natural products, chemicals, metabolites, and synthetic compounds. A large majority of these products, in particular commonly used antiinflammatory drugs such as corticosteroids and the nonsteroidal antiinflammatory drugs (NSADDs) aspirin, sulindac, ibuprofen and sulphasalazine, have the ability to partially inhibit NF-kB activity in cell culture. However, the precise mechanism of action and the specific molecular targets of most of these inhibitors remain unclear. 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

C,H2N02 372-09-8) see Cyclopentamine Levorphanol Pyrantel Sulindac cyanoacetyl chloride... 

C10H9FO 37794-19-7) see Sulindac 5-fluoro-2-methyl-177-indene-3-acetic acid (C,2H, F02 32004-66-3) see Sulindac... 

C HiqOj 123-62-6) see Alclometasone dipropionate Alfentanil Alphaprodine Beclometasone Dextropropoxyphene Diethylstilbestrol dipropionate Fentanyl Propiram Sulindac Testosterone propionate propanol... 

SUGANUMA M, OKABE s, KAi Y, suEOKA N, suEOKA E and FUJiKi H (1999) Synergistic effects of (-)-epigallocatechin gallate with (-)-epicatechin, sulindac, or tamoxifen on cancer-preventive activity in human lung cancer cell line PC-9 , Cancer Res, 59, 44-7. 

In the early clinical trials of Pravadoline (248), the Sterling-Winthrop Research group observed CNS side effects. In an effort to circumvent these issues, indenes were explored as an alternative core [197]. The rationale behind this approach came from the observation that sulindac (308), an indene analogue of indomethacin (309), had anti-inflammatory properties comparable to (309) but without the CNS-associated side effects. 

Allopurinol, barbiturates, carbamazepine, cephalosporins, cyclophosphamide, ethambutol, fluconazole, ibuprofen, lamotrigine, macrolides, nitrofurantoin, penicillins, phenytoin, propranolol, quinolones, sulfonamide antimicrobials, sulindac, tetracyclines, thiazides, valproic acid, and vancomycin... 

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