Diphenylcyclopropenone

Diphenylcyclopropenone
Names
Preferred IUPAC name
2,3-Diphenylcycloprop-2-en-1-one
Other names
Diphencyprone, DPCP, DPC
Identifiers
CAS Number
  • 886-38-4 checkY
3D model (JSmol)
  • Interactive image
ChemSpider
  • 58568
ECHA InfoCard 100.011.772 Edit this at Wikidata
PubChem CID
  • 65057
UNII
  • I7G14NW5EC
CompTox Dashboard (EPA)
  • DTXSID2046545 Edit this at Wikidata
InChI
  • InChI=1S/C15H10O/c16-15-13(11-7-3-1-4-8-11)14(15)12-9-5-2-6-10-12/h1-10H
  • O=C2C(=C2\c1ccccc1)\c3ccccc3
Properties
Chemical formula
 C15H10O
Molar mass 206.244 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
Chemical compound

Diphenylcyclopropenone (diphencyprone) is a topically administered experimental drug intended for treating alopecia areata and alopecia totalis.[1] Topical immunotherapy using diphenylcyclopropenone may also be an effective treatment option for recalcitrant warts.[2] It is not approved by either the Food and Drug Administration or the European Medicines Agency.[3]

Mechanism of action

Diphenylcyclopropenone triggers an immune response that is thought to oppose the action of the autoreactive cells that otherwise cause hair loss.[4] One hypothesis is that in response to DPCP treatment, the body will attempt to downregulate inflammation through a variety of pathways, resulting in a downregulation of the autoimmune response at the hair follicle. This autoinflammatory reaction would otherwise destroy body's hair follicles.[3]

Studies

A study of 41 alopecia areata patients showed significant hair regrowth in 40% at 6 months, being sustained in two thirds of these after a 12-month-follow up-period.[5]

In a 2002 study for the treatment of warts, the responders consisted of 135 individuals (87.7%) that had complete clearance of warts. Reported adverse effects were local and included with pruritus (itching) (15.6%), with blistering (7.1%), and with eczematous reactions (eczema)(14.2%). The majority of the patients tolerated the treatment very well. One patient developed local impetigo (minor infection). Patients had an average of 5 treatments over a 6-month period.[2]

Chemical properties

The chemical properties of diphenylcyclopropenone are dominated by the strong polarization of the carbonyl group, which gives a partial positive charge with aromatic stabilization on the cyclopropene (cyclopropenium) ring and a partial negative charge on oxygen. The steric hindrance and partial charge on the cyclopropenium inhibit further electrophilic aromatic substitution there, but the phenyl rings are reactive. The cyclopropenium acts as a meta director.[6]

Electrophilic Lewis acids stabilize the charge separation, forming diphenylcyclopropenium ether or ester salts. Such compounds are extremely reactive electrophiles.[6]

Conversely, the oxygen is quite nucleophilic. Lux-Flood acids can abstract the oxygen: thus activated isocyanates effect imines; phosphorus sulfides or activated thioic acids effect the thione,[6] and a wide variety of electrophilic chlorinators, including oxalyl chloride, thionyl chloride, and phosphorus pentachloride, effect 3,3‑dichloro-1,2‑diphenyl­cyclopropene. The latter sees primary application as an electrophilical chlorinator itself,[7] and catalyzes the action of the aforementioned chlorinators.[6] However, 3,3‑dichloro-1,2‑diphenyl­cyclopropene also ligates palladium for cross-coupling reactions,[7] and reacts with trichloroacetate to give diphenylcyclobutenedione upon aqueous workup.[6]

In other respects, the carbonyl is a typical electrophile, adding Grignard reagents, Knoevenagel enols, and enamines. The central ring is highly strained, and the presence of most transition metals or heating to 160 °C induces decarbonylation, although heating just below the decarbonylation temperature (150 °C) irreversibly forms a [3+2] dimer instead. Soft nucleophiles that typically add in conjugate typically open the ring instead, as do naïve attempts at reduction. However, careful hydroboration can reduce away the carbonyl.[6]

See also

References

  1. ^ Singh G, Lavanya M (January 2010). "Topical immunotherapy in alopecia areata". International Journal of Trichology. 2 (1): 36–9. doi:10.4103/0974-7753.66911. PMC 3002409. PMID 21188022.
  2. ^ a b Upitis JA, Krol A (2002). "The use of diphenylcyclopropenone in the treatment of recalcitrant warts". Journal of Cutaneous Medicine and Surgery. 6 (3): 214–7. doi:10.1007/s10227-001-0050-9. PMID 11951129. S2CID 38571189.
  3. ^ a b Bulock KG, Cardia JP, Pavco PA, Levis WR (November 2015). "Diphencyprone Treatment of Alopecia Areata: Postulated Mechanism of Action and Prospects for Therapeutic Synergy with RNA Interference". The Journal of Investigative Dermatology. Symposium Proceedings. 17 (2): 16–8. doi:10.1038/jidsymp.2015.33. PMID 26551938.
  4. ^ Public summary of positive opinion for orphan designation of diphenylcyclopropenone for the treatment of alopecia totalis Archived 22 December 2017 at the Wayback Machine, European Medicines Agency. Document Date: London, 23 April 2009. Doc.Ref.:EMEA/COMP/428277/2006
  5. ^ Sotiriadis D, Patsatsi A, Lazaridou E, Kastanis A, Vakirlis E, Chrysomallis F (January 2007). "Topical immunotherapy with diphenylcyclopropenone in the treatment of chronic extensive alopecia areata". Clinical and Experimental Dermatology. 32 (1): 48–51. doi:10.1111/j.1365-2230.2006.02256.x. PMID 17004987. S2CID 43725892.
  6. ^ a b c d e f Lambert, Tristan H.; Nacsa, Eric D. "Diphenylcyclopropenone". Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289X.rn01532.
  7. ^ a b Bennett, Clay S. (2012). "3,3-Dichloro-1,2-diphenylcyclopropene". Encyclopedia of Reagents for Organic Synthesis. John Wiley & Sons. doi:10.1002/047084289x.rn01514. ISBN 978-0471936237.