Salsalate

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Salsalate
Salsalate.svg
Systematic (IUPAC) name
2-(2-Hydroxybenzoyl)oxybenzoic acid
Clinical data
Trade names Disalcid, Salflex
AHFS/Drugs.com monograph
MedlinePlus a682880
Pregnancy
category
  • US: C (Risk not ruled out)
Legal status
Identifiers
CAS Number 552-94-3 YesY
ATC code N02BA06
PubChem CID 5161
DrugBank DB01399 YesY
ChemSpider 4977 N
UNII V9MO595C9I YesY
KEGG D00428 N
ChEBI CHEBI:9014 N
Chemical data
Formula C14H10O5
Molar mass 258.23 g/mol
 NYesY (what is this?)  (verify)

Salsalate is a medication that belongs to the salicylate and non-steroidal anti-inflammatory drug (NSAID) classes. Relative to other NSAIDs, salsalate has a weak inhibitory effect on the cyclooxygenase enzyme and decreases the production of several proinflammatory chemical signals such as interleukin-6, TNF-alpha, and C-reactive protein.[1] The mechanism through which salsalate is thought to reduce the production of these inflammatory chemical signals is through the inhibition of IκB kinase resulting in decreased action of NF-κB genes.[1][2][3] This mechanism is thought to be responsible for salsalate's insulin-sensitizing and blood sugar lowering properties.[2] Salsalate is the generic name of a prescription drug marketed under the brandnames Mono-Gesic, Salflex, Disalcid, and Salsitab. Other generic and brand name formulations may be available.[4]

Medical uses[edit]

Salsalate may be used for inflammatory disorders such as rheumatoid arthritis or noninflammatory disorders such as osteoarthritis.[1][5]

Safety[edit]

The risk of bleeding is a common concern with use of the NSAID class of medications. However, the bleeding risk associated with salsalate is lower than that associated with aspirin use.[2]

Research[edit]

Salsalate has been proposed for the prevention and treatment of type 2 diabetes mellitus due to its ability to lower insulin resistance associated with inflammation and may be useful in prediabetes.[1] However, the use of salsalate to prevent the progression from prediabetes to type 2 diabetes mellitus has received limited study.[1]

History[edit]

Salsalate had been suggested as possible treatment for diabetes as early as 1876.[1][6][7]

Synthesis[edit]

Unquestionably, the most frequently used analgesic is aspirin. The reader will recall that aspirin is regarded as a latentiated form of salicyclic acid and is intented to minimize as far as possible the irritation of the gastrointestinal tract that salicyclic acid would otherwise cause. Salsalate represents another approach to this problem in which self-esterification has been used to serve the same purpose. Direct self-condensation is difficult to control, although low temperature treatment of salicylic acid with PCl3 does work.

Salsalate synthesis:[8][9] DE 211403  and DE 214044  (1909, both to Boehringer, Mann.), Frdl. 9, 928 and C.A. 4, 368 (1910).

A more stepwise procedure involves the condensation of benzyl salicylate (1) with the acid chloride of salicyclate benzyl ether 2 to produce protected dimer 3. Catalytic hydrogenation removes the benzyl groups and completes the preparation of salsalate (4).

NB: Salsalate is an example of a Depside.

References[edit]

  1. ^ a b c d e f Anderson K, Wherle L, Park M, Nelson K, Nguyen L (June 2014). "Salsalate, an old, inexpensive drug with potential new indications: a review of the evidence from 3 recent studies". Am Health Drug Benefits 7 (4): 231–5. PMC 4105730. PMID 25126374. 
  2. ^ a b c Esser N, Paquot N, Scheen AJ (March 2015). "Anti-inflammatory agents to treat or prevent type 2 diabetes, metabolic syndrome and cardiovascular disease". Exp Opin Investig Drugs (Review) 24 (3): 283–307. doi:10.1517/13543784.2015.974804. PMID 25345753. 
  3. ^ Ridker PM, Lüscher TF (July 2014). "Anti-inflammatory therapies for cardiovascular disease". Eur Heart Journal 35 (27): 1782–91. doi:10.1093/eurheartj/ehu203. PMC 4155455. PMID 24864079. 
  4. ^ drugs.com Salsalate entry
  5. ^ Hardie DG (July 2013). "AMPK: a target for drugs and natural products with effects on both diabetes and cancer". Diabetes 62 (7): 2164–72. doi:10.2337/db13-0368. PMC 3712072. PMID 23801715. 
  6. ^ Powell, Kendall (May 31, 2007). "The Two Faces of Fat". Nature 447 (7144): 525–7. doi:10.1038/447525a. PMID 17538594. 
  7. ^ Ebstein, W (1876). "Zur therapie des diabetes mellitus, insbesondere uber die anwendung des salicylsauren natron bei demselben". Berliner Klinische Wochenschrift 13: 337–340. 
  8. ^ Cavallito, Chester J.; Buck, Johannes S. (1943). "Synthesis of Phenolic Acid Esters. I. Depsides1". Journal of the American Chemical Society 65 (11): 2140. doi:10.1021/ja01251a034. 
  9. ^ Baker, Wilson; Ollis, W. D.; Zealley, T. S. (1951). "42. Eight- and higher-membered ring compounds. Part II. Di-, tri-, tetra-, and hexa-salicylides". Journal of the Chemical Society (Resumed): 201. doi:10.1039/JR9510000201.