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Revision as of 18:21, 9 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 466262139 of page Sulindac for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').		Latest revision as of 07:55, 17 June 2023 edit Boghog (talk | contribs)Autopatrolled, Extended confirmed users, IP block exemptions, New page reviewers, Pending changes reviewers, Rollbackers, Template editors137,804 editsm →Synthesis: moved graphic to left
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			{{Short description|Nonsteroidal anti-inflammatory drug (NSAID)}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Verifiedfields = changed
			| Watchedfields = changed
	| verifiedrevid = 402677877		| verifiedrevid = 470474499
	| IUPAC_name = {(1''Z'')-5-fluoro-2-methyl-1--1H-indene-3-yl}acetic acid		| IUPAC_name = {(1''Z'')-5-fluoro-2-methyl-1--1H-indene-3-yl}acetic acid
	| image = Sulindac structure.svg		| image = Sulindac structure.svg
	<!--Clinical data-->		<!--Clinical data-->
	| tradename = Clinoril		| tradename = Clinoril
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	| pregnancy_AU = C		| pregnancy_AU = C
	| pregnancy_US = C		| pregnancy_US = C
			| legal_AU = S4
	| legal_UK = POM		| legal_UK = POM
	| legal_US = Rx-only		| legal_US = Rx-only
	| routes_of_administration = Oral		| routes_of_administration = ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability = Approximately 90% (Oral)		| bioavailability = Approximately 90% (Oral)
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	| elimination_half-life = 7.8 hours, metabolites up to 16.4 hours		| elimination_half-life = 7.8 hours, metabolites up to 16.4 hours
	| excretion = ] (50%) and fecal (25%)		| excretion = ] (50%) and fecal (25%)
	<!--Identifiers-->		<!--Identifiers-->
			| IUPHAR_ligand = 5425
	| CASNo_Ref = {{cascite|correct|CAS}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 38194-50-2		| CAS_number = 38194-50-2
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	| UNII_Ref = {{fdacite|correct|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 184SNS8VUH		| UNII = 184SNS8VUH
	| KEGG_Ref = {{keggcite|changed|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D00120		| KEGG = D00120
	| ChEBI_Ref = {{ebicite|changed|EBI}}		| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 9352		| ChEBI = 9352
	| ChEMBL_Ref = {{ebicite|changed|EBI}}		| ChEMBL_Ref = {{ebicite|changed|EBI}}
	| ChEMBL = <!-- blanked - oldvalue: 15770 -->		| ChEMBL = 15770
			| PDB_ligand = SUZ
⚫	| C=20 | H=17 | F=1 | O=3 | S=1
			<!--Chemical data-->
	| molecular_weight = 356.412 g/mol
		⚫	| C=20 | H=17 | F=1 | O=3 | S=1
	| smiles = O=S(c1ccc(cc1)\C=C3/c2ccc(F)cc2\C(=C3C)CC(=O)O)C		| smiles = O=S(c1ccc(cc1)\C=C3/c2ccc(F)cc2\C(=C3C)CC(=O)O)C
	| InChI = 1/C20H17FO3S/c1-12-17(9-13-3-6-15(7-4-13)25(2)24)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-
	| InChIKey = MLKXDPUZXIRXEP-MFOYZWKCBF
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 1S/C20H17FO3S/c1-12-17(9-13-3-6-15(7-4-13)25(2)24)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-		| StdInChI = 1S/C20H17FO3S/c1-12-17(9-13-3-6-15(7-4-13)25(2)24)16-8-5-14(21)10-19(16)18(12)11-20(22)23/h3-10H,11H2,1-2H3,(H,22,23)/b17-9-
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = MLKXDPUZXIRXEP-MFOYZWKCSA-N		| StdInChIKey = MLKXDPUZXIRXEP-MFOYZWKCSA-N
			| melting_point = 182
			| melting_high = 185
			| melting_notes = (decomp.)
	}}		}}
			<!-- Definition and medical uses -->
			'''Sulindac''' is a ] (NSAID) of the arylalkanoic acid class that is marketed as '''Clinoril'''. Imbaral (not to be confused with ]) is another name for this drug. Its name is derived from sul(finyl)+ ind(ene)+ ac(etic acid)
			<!-- Society and culture -->
			It was patented in 1969 and approved for medical use in 1976.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title= Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=517 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA517 |language=en}}</ref>
			==Medical uses==
			Like other NSAIDs, it is useful in the treatment of ] or ] ] conditions. Sulindac is a ], derived from ], that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAIDs except for drugs of the ] class.<ref>{{Cite book | chapter = Sulindac | title = LiverTox: Clinical and Research Information on Drug-Induced Liver Injury . | location = Bethesda (MD) | publisher = National Institute of Diabetes and Digestive and Kidney Diseases | date = 2012 | pmid = 31643638 | chapter-url = https://pubmed.ncbi.nlm.nih.gov/31643638/ }}</ref> The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting ] synthesis.
			Its usual ] is 150-200 ]s twice per day, with food. It should not be used by persons with a history of major allergic reactions (] or ]) to ] or other NSAIDs, and should be used with caution by persons having pre-existing ] disease. Sulindac is much more likely than other NSAIDs to cause damage to the liver or pancreas, though it is less likely to cause kidney damage than other NSAIDs.
			Sulindac seems to have a property, independent of COX-inhibition, of reducing the growth of polyps and precancerous lesions in the colon, especially in association with ], and may have other anti-cancer properties.<ref>{{cite journal | vauthors = Scheper MA, Nikitakis NG, Chaisuparat R, Montaner S, Sauk JJ | title = Sulindac induces apoptosis and inhibits tumor growth in vivo in head and neck squamous cell carcinoma | journal = Neoplasia | volume = 9 | issue = 3 | pages = 192–199 | date = March 2007 | pmid = 17401459 | pmc = 1838577 | doi = 10.1593/neo.06781 | url = http://www.neoplasia.com/abstract.php?msid=1062 | url-status = dead | archive-url = https://archive.today/20120905174725/http://www.neoplasia.com/abstract.php?msid=1062 | archive-date = 2012-09-05 }}</ref><ref>{{cite journal | vauthors = Shiff SJ, Qiao L, Tsai LL, Rigas B | title = Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells | journal = The Journal of Clinical Investigation | volume = 96 | issue = 1 | pages = 491–503 | date = July 1995 | pmid = 7615821 | pmc = 185223 | doi = 10.1172/JCI118060 }}</ref>
			== Adverse effects ==
			In October 2020, the U.S. ] (FDA) required the ] to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.<ref name="FDA PR 20201015" /><ref name="FDA safety 20201015" /> They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.<ref name="FDA PR 20201015">{{cite press release | title=FDA Warns that Using a Type of Pain and Fever Medication in Second Half of Pregnancy Could Lead to Complications | website=U.S. ] (FDA) | date=15 October 2020 | url=https://www.fda.gov/news-events/press-announcements/fda-warns-using-type-pain-and-fever-medication-second-half-pregnancy-could-lead-complications | access-date=15 October 2020}} {{PD-notice}}</ref><ref name="FDA safety 20201015">{{cite web | title=NSAIDs may cause rare kidney problems in unborn babies | website=U.S. Food and Drug Administration | date=21 July 2017 | url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-recommends-avoiding-use-nsaids-pregnancy-20-weeks-or-later-because-they-can-result-low-amniotic | access-date=15 October 2020}} {{PD-notice}}</ref>
			==Society and culture==
			===Litigation===
			In September 2010 a federal jury in New Hampshire awarded $21 million to Karen Bartlett, a woman who developed ]/] as a result of taking a generic brand of sulindac manufactured by Mutual Pharmaceuticals for her shoulder pain. Ms. Bartlett sustained severe injuries including the loss of over 60% of her surface skin and permanent near-blindness. The case had been appealed to the United States Supreme Court, where the main issue was whether federal law preempts Ms. Bartlett's claim.<ref>{{cite news| vauthors = Thomas K |title=Justices to Take Up Case on Generic Drug Markers' Liability|url=https://www.nytimes.com/2013/03/05/business/justices-to-take-up-case-on-generic-drug-makers-liability.html|newspaper=New York Times|access-date=4 March 2013|date=2013-03-04}}</ref> On June 24, 2013, the Supreme Court ruled 5–4 in favor of Mutual Pharmaceuticals, throwing out the earlier $21 million jury verdict.<ref>{{cite web| vauthors = Kendall B |title=Supreme Court Again Limits Product-Liability Suits on Generic Drugs|url=https://online.wsj.com/article/BT-CO-20130624-706631.html?mod=googlenews_wsj|publisher=Wall Street Journal|access-date=24 June 2013}}</ref><!-- ORIGINALLY WAS: "Bartlett v. Mut. Pharm. Co., Inc., 678 F.3d 30, 34 (1st Cir. 2012)." -->
			<ref>{{cite court
			|litigants= Bartlett v. Mut. Pharm. Co., Inc.
			|vol=678
			|reporter=F.3d
			|opinion=30
			|court=D.C. Cir.
			|date=March 19, 2013
			|url=https://www.law.cornell.edu/supct/cert/12-142
			|access-date=September 3, 2017
			}}</ref>
			===Synthesis===
			]
			Rxn of ''p''-fluorobenzyl chloride ('''1''') with the anion of diethylmethyl malonate ('''2''') gives intermediate diester ('''3'''), saponification of which and subsequent decarboxylation leads to '''4'''. {Alternatively it can be formed by ] between p-] and ] in the presence of ], followed by ] of the olefinic bond using a palladium on carbon catalyst.}
			] (PPA) cyclization leads to 5-fluoro-2-methyl-3-] ('''4'''). A ] with ] ] and bromoacetic ester leads to carbinol ('''5'''), which is then dehydrated with ] to indene '''6'''. {Alternatively, this step can be performed in a ] with ], which is then further decarboxylated.}
			The active methylene group is condensed with ''p''-], using ] as catalyst, and then saponified to give ] ('''7''') which in turn oxidized with ] to sulfoxide '''8''', the ] agent sulindac.
			== References ==
			{{Reflist}}
			== External links ==
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			{{Anti-inflammatory and antirheumatic products}}
			{{Prostanoidergics}}
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