Diphenylcyclopropenone

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Contents

Diphenylcyclopropenone
Diphenylcyclopropenone.svg
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 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • 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
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).

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 3,3dichloro-1,2diphenyl­cyclopropene. The latter sees primary application as an electrophilical chlorinator itself, [7] and catalyzes the action of the aforementioned chlorinators. [6] However, 3,3dichloro-1,2diphenyl­cyclopropene 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

Related Research Articles

<span class="mw-page-title-main">Alopecia areata</span> Medical condition

Alopecia areata, also known as spot baldness, is a condition in which hair is lost from some or all areas of the body. It often results in a few bald spots on the scalp, each about the size of a coin. Psychological stress and illness are possible factors in bringing on alopecia areata in individuals at risk, but in most cases there is no obvious trigger. People are generally otherwise healthy. In a few cases, all the hair on the scalp is lost, or all body hair is lost. Hair loss can be permanent, or temporary.

<span class="mw-page-title-main">Hair loss</span> Loss of hair from the head or body

Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarring is not usually present. Hair loss in some people causes psychological distress.

<span class="mw-page-title-main">Hair follicle</span> Organ found in the dermal layer of the mammalian skin that regulates hair growth

The hair follicle is an organ found in mammalian skin. It resides in the dermal layer of the skin and is made up of 20 different cell types, each with distinct functions. The hair follicle regulates hair growth via a complex interaction between hormones, neuropeptides, and immune cells. This complex interaction induces the hair follicle to produce different types of hair as seen on different parts of the body. For example, terminal hairs grow on the scalp and lanugo hairs are seen covering the bodies of fetuses in the uterus and in some newborn babies. The process of hair growth occurs in distinct sequential stages: anagen is the active growth phase, catagen is the regression of the hair follicle phase, telogen is the resting stage, exogen is the active shedding of hair phase and kenogen is the phase between the empty hair follicle and the growth of new hair.

An ylide or ylid is a neutral dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both atoms have full octets of electrons. The result can be viewed as a structure in which two adjacent atoms are connected by both a covalent and an ionic bond; normally written X+–Y. Ylides are thus 1,2-dipolar compounds, and a subclass of zwitterions. They appear in organic chemistry as reagents or reactive intermediates.

<span class="mw-page-title-main">Paraben</span> Class of chemical compounds; esters of parahydroxybenzoic acid

Parabens are chemicals that are commonly used as preservatives in cosmetic and pharmaceutical products. Chemically, they are a series of parahydroxybenzoates or esters of parahydroxybenzoic acid. Research is being conducted to evaluate the potential health implications of paraben usage.

<span class="mw-page-title-main">Telogen effluvium</span> Medical condition

Telogen effluvium is a scalp disorder characterized by the thinning or shedding of hair resulting from the early entry of hair in the telogen phase. It is in this phase that telogen hairs begin to shed at an increased rate, where normally the approximate rate of hair loss is 125 hairs per day.

<span class="mw-page-title-main">Alopecia universalis</span> Medical condition

Alopecia universalis(AU), also known as alopecia areata universalis, is a medical condition involving the loss of all body hair, including eyebrows, eyelashes, chest hair, armpit hair, and pubic hair. It is the most severe form of alopecia areata (AA). People with the condition are usually healthy and have no other symptoms and a normal life expectancy.

<span class="mw-page-title-main">Enolate</span> Organic anion formed by deprotonating a carbonyl (>C=O) compound

In organic chemistry, enolates are organic anions derived from the deprotonation of carbonyl compounds. Rarely isolated, they are widely used as reagents in the synthesis of organic compounds.

<span class="mw-page-title-main">Alopecia totalis</span> Medical condition

Alopecia totalis is the loss of all hair on the head and face. Its causes are unclear, but believed to be autoimmune. Research suggests there may be a genetic component linked to developing alopecia totalis; the presence of DRB1*0401 and DQB1*0301, both of which are human leukocyte antigens (HLA), were found to be associated with long-standing alopecia totalis.

Squaric acid, also called quadratic acid because its four carbon atoms approximately form a square, is a diprotic organic acid with the chemical formula C4O2(OH)2.

<span class="mw-page-title-main">Nucleophilic conjugate addition</span> Organic reaction

Nucleophilic conjugate addition is a type of organic reaction. Ordinary nucleophilic additions or 1,2-nucleophilic additions deal mostly with additions to carbonyl compounds. Simple alkene compounds do not show 1,2 reactivity due to lack of polarity, unless the alkene is activated with special substituents. With α,β-unsaturated carbonyl compounds such as cyclohexenone it can be deduced from resonance structures that the β position is an electrophilic site which can react with a nucleophile. The negative charge in these structures is stored as an alkoxide anion. Such a nucleophilic addition is called a nucleophilic conjugate addition or 1,4-nucleophilic addition. The most important active alkenes are the aforementioned conjugated carbonyls and acrylonitriles.

In organic chemistry, umpolung or polarity inversion is the chemical modification of a functional group with the aim of the reversal of polarity of that group. This modification allows secondary reactions of this functional group that would otherwise not be possible. The concept was introduced by D. Seebach and E.J. Corey. Polarity analysis during retrosynthetic analysis tells a chemist when umpolung tactics are required to synthesize a target molecule.

Ophiasis is a form of alopecia areata characterized by the loss of hair in the shape of a wave at the circumference of the head.

<span class="mw-page-title-main">Loose anagen syndrome</span> Medical condition

Loose anagen syndrome, also known as loose anagen hair syndrome, is a hair disorder related to dermatology. It is characterised by the easy and pain free detachment of anagen staged hairs from the scalp. This hair condition can be spontaneous or genetically inherited.

Scarring hair loss, also known as cicatricial alopecia, is the loss of hair which is accompanied with scarring. This is in contrast to non scarring hair loss.

Non scarring hair loss, also known as noncicatricial alopecia is the loss of hair without any scarring being present. There is typically little inflammation and irritation, but hair loss is significant. This is in contrast to scarring hair loss during which hair follicles are replaced with scar tissue as a result of inflammation. Hair loss may be spread throughout the scalp (diffuse) or at certain spots (focal). The loss may be sudden or gradual with accompanying stress.

<span class="mw-page-title-main">Cyclopropenone</span> Chemical compound

Cyclopropenone is an organic compound with molecular formula C3H2O consisting of a cyclopropene carbon framework with a ketone functional group. It is a colorless, volatile liquid that boils near room temperature. Neat cyclopropenone polymerizes upon standing at room temperature, and chemical vendors typically supply it as an acetal. The chemical properties of the compound are dominated by the strong polarization of the carbonyl group, which gives a partial positive charge with aromatic stabilization on the ring and a partial negative charge on oxygen. It is an aromatic compound.

Frictional alopecia is the loss of hair that is caused by rubbing of the hair, follicles, or skin around the follicle. The most typical example of this is the loss of ankle hair among people who wear socks constantly for years. The hair may not grow back even years after the source of friction has ended.

<span class="mw-page-title-main">Togni reagent II</span> Chemical compound

Togni reagent II is a chemical compound used in organic synthesis for direct electrophilic trifluoromethylation.

<span class="mw-page-title-main">Dibutyl squarate</span> Chemical compound

Dibutyl squarate (also known as squaric acid dibutyl ester or SADBE) is a chemical compound with the molecular formula C12H18O4. It is the dibutyl derivative of squaric acid.

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. 1 2 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. 1 2 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. 1 2 3 4 5 6 Lambert, Tristan H.; Nacsa, Eric D. "Diphenylcyclopropenone". Encyclopedia of Reagents for Organic Synthesis . John Wiley & Sons. doi:10.1002/047084289X.rn01532.
  7. 1 2 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.