Diphenylcyclopropenone
Chemical compound
From Wikipedia, the free encyclopedia
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]
| |
| Names | |
|---|---|
| Preferred IUPAC name
2,3-Diphenylcycloprop-2-en-1-one | |
| Other names
Diphencyprone, DPCP, DPC | |
| Identifiers | |
3D model (JSmol) |
|
| ChemSpider | |
| ECHA InfoCard | 100.011.772 |
PubChem CID |
|
| UNII | |
CompTox Dashboard (EPA) |
|
| |
| |
| Properties | |
| 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).
| |
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 electrophilic chlorinator itself,[7] and catalyzes the action of the aforementioned chlorinators.[6]
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 will open the ring, as do naïve reductions. However, careful hydroboration can reduce away the carbonyl.[6]