The 2,3-diesters of 6-substituted-2,3-dihydroxy-1,4-naphthoquinones exhibit useful anti-psoriatic activity in mammals.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to novel naphthoquinone compositions and the 
pharmaceutical use of the naphthoquinones in treating psoriasis in a 
mammal. 
2. Prior Art 
Psoriasis is a skin disease characterized in part by excessive 
proliferation of cells of the epidermis which remain strongly adherent and 
build up into a scaly plaque typical of the disease. Currently available 
therapies, which are not curative, depend on the control of epidermal cell 
proliferation through the use of hormonal agents, such as corticosteroids, 
or through the use of compounds related to cancer chemotherapy such as 
hydroxyurea, methotrexate, and the nitrogen mustards. 
While the above agents are effective to a certain extent, they cause 
numerous severe undesirable side effects both locally and systemically. 
Certain naphthoquinones which are chemically related to the compound of 
this invention are known. For example, the compound 
6-bromo-2,3-dihydroxy-1,4naphthoquinone has been reported by Weygand, 
German Pat. No. 859,008. While this compound is recognized as a valuable 
intermediate for the preparation of dyestuffs, no useful biological 
activity has been ascribed to it. Specifically, any suggestion that this 
compound might have anti-psoriatic activity has not been advanced. 
Related naphthoquinones having antifungal and antibacterial activity can be 
found in U.S. Pat. No. 3,914,264 and West German Offenlegungschrift Nos. 
2,135,712, 2,456,655 and 2,520,739. However, none of these disclosures 
have recognized the use of these or related naphthoquinone compositions as 
anti-psoriatic agents. 
It is also suggested that certain related compounds have antimalarial 
activitu, e.g. 6-chloro-2-hydroxy-1,4-naphthoquinone, 
7-chloro-2-hydroxy-1,4-naphthoquinone and 
6-chloro-1,2,4-triacetoxynaphthoquinone. See L. F. Fieser and R. H. Brown, 
J. Am. Chem. Soc. 71, 3615-3617 (1949). 
It has now been discovered that the 2,3-diesters of 
6-substituted-2,3-dihydroxy-1,4-naphthoquinone are effective in preventing 
epidermal cell proliferation when topically applied to a mammal. More 
specifically, it is effective as an anti-psoriatic agent in humans. 
In its broadest aspect, the present invention is a pharmaceutical 
composition comprising at least one pharmaceutically acceptable excipient 
and a 2,3-diester of a 6-substituted-2,3-dihydroxy-1,4-naphthoquinone 
represented by Formula (I), below, 
##STR1## 
wherein R is hydrogen, halo, cyano, C.sub. 1 to C.sub. 18 linear or 
branched alkoxy and R.sup.1 is an alkyl of 1-5 carbon atoms. Preferably R 
is halo (particularly chloro) and R.sup.1 is alkyl of 1 or 2 carbon atoms. 
Another aspect of this invention is a method for preventing epidermal cell 
proliferation in a mammal which comprises topically administering a 
composition of the invention to a mammal in need of such treatment. 
Formulation and Administration 
The compounds useful in the present invention are formulated for 
administration in any convenient way by analogy with other topical 
compositions. These compositions may be presented for use in any 
conventional manner with the aid of any of a wide variety of 
pharmaceutical excipients. 
Generally, the psoriatic manifestation in mammals, particularly humans, is 
combatted by contacting the afflicted area with a therapeutically 
effective amount of the naphthoquinone-containing composition of this 
invention, that is, an amount which reduces the proliferation of epidermal 
cells (an anti-psoriatic effect). Preferably, the naphthoquinone is first 
formulated to prepare a suitable pharmaceutical formulation, as discussed 
hereinafter, which is then placed in contact with an afflicted area. An 
effective amount of the naphthoquinone will depend upon the particular 
condition and the mammal receiving the treatment and will vary between 
0.001% to 10% by weight of the pharmaceutical composition and preferably 
will be between 0.01% and 1% by weight of the formulation. Using these 
levels in the formulation, a therapeutically effective and non-side effect 
producing amount, i.e. enough to effect an anti-psoriatic response, but 
not enough to adversely effect the recipient, is applied to the afflicted 
area(s). 
The naphthoquinone of this invention may be formulated with suitable 
pharmaceutical vehicles known in the art to form particularly effective 
topical compositions. As disclosed above, an effective amount of the 
naphthoquinone is about 0.001% w to about 10% w of the total formulated 
composition. The rest of the formulated composition will be about 90% w to 
about 99.999% w of at least one suitable pharmaceutical excipient which 
may include a pharmaceutically acceptable solvent and other 
pharmaceutically acceptable additives to form a topically effective 
pharmaceutical formulation. 
A pharmaceutically acceptable solvent is one which is substantially 
non-toxic and non-irritating under the conditions used and may be readily 
formulated into any of the classical drug formulations such as powders, 
creams, ointments, lotions, gels, foams, aerosols, solutions and the like. 
Particularly suitable solvents include water, ethanol, acetone, glycerine, 
propylene carbonate, dimethylsulfoxide (DMSO), and glycols such as 
1,2-propylene diol, i.e., propylene glycol, 1,3-propylene diol, 
polyethylene glycol having a molecular weight of from 100 to 10,000, 
dipropylene glycol, etc. and mixtures of the aforementioned solvents with 
each other. 
A topical cream may be prepared as a semi-solid emulsion of oil in water or 
water in oil. A cream base formulation by definition is an emulsion, which 
is a two-phase system with one liquid (for example fats or oils) being 
dispersed as small globules in another substance (e.g., a glycol-water 
solvent phase) which may be employed as the primary solvent for the 
naphthoquinones therein. The cream formulation may contain fatty alcohols, 
surfactants, mineral oil or petrolatum and other typical pharmaceutical 
adjuvants such as anti-oxidants, antiseptics, or compatible adjuvants. A 
typical cream base formulation is as follows: 
Water/glycol mixture (15% or more glycol): 50-99 parts by weight 
Fatty Alcohol: 1-20 
Non-ionic Surfactant: 0-10 
Mineral Oil: 0-10 
Typical Pharmaceutical Adjuvants: 0-5 
Active Ingredients: 0.001-10 
The fatty alcohol, non-ionic surfactant, and other adjuvants are discussed 
in U.S. Pat. No. 3,934,013 to Poulsen which is incorporated herein by 
reference. 
The naphthoquinones of this invention may also be formulated as topical 
ointments. A "classical" ointment is a semisolid anhydrous composition 
which may contain mineral oil, white petrolatum, a suitable solvent such 
as a glycol and may include propylene carbonate and other pharmaceutically 
suitable additives such as surfactants, for example Span and Tween, or 
wool fat (lanolin), along with stabilizers such as antioxidants and other 
adjuvants as mentioned before. Following is an example of a typical 
"classical" ointment base: 
White Petrolatum: 40-94 parts by weight 
Mineral Oil: 5-20 
Glycol Solvent: 1-15 
Surfactant: 0-10 
Stabilizer: 0-10 
Active Ingredients: 0.001-10.0 
Other suitable ointment base formulations which employ propylene carbonate 
are described in U.S. Pat. No. 4,017,615 issued Apr. 12, 1977 by Shastri 
et al entitled "Propylene Carbonate Ointment Vehicle" and U.S. Pat. No. 
3,924,004 issued Dec. 2, 1975 by Chang et al entitled "Fatty 
Alcohol-Propylene Carbonate-Glycol Solvent Cream Vehicle". As much of 
those applications as is pertinent is incorporated herein by reference. 
Following is a typical ointment base formulation containing propylene 
carbonate: 
Active Ingredients: 0.001-10.0 parts by weight 
Propylene Carbonate: 1-10 
Solvent: 1-10 
Surfactant: 0-10 
White Petrolatum: 70-97 
Suitable solvents, surfactants, stabilizers, etc. are discussed in U.S. 
Pat. No. 3,934,013 and such are incorporated herein by reference. 
A suitable topical "non-classical" anhydrous, water washable "ointment 
type" base is described in U.S. Pat. No. 3,592,930 to Katz and Neiman, and 
that patent is incorporated herein by reference. A representative 
composition of this invention utilizing such base is as follows: 
Glycol Solvent: 40-35 parts by weight 
Fatty Alcohol: 15-45 
Compatible Plasticizer: 0-15 
Compatible Coupling Agent: 0-15 
Penetrant: 0-20 
Active Ingredients: 0.001-10.0 
Process For Preparation 
The naphthoquinones represented by Formula (I) wherein R is hydrogen, halo, 
cyano or C.sub.1 -C.sub.18 alkoxy are prepared by following, in principle, 
the process disclosed in the aforesaid Weygand Patentshrift and 
illustrated by the following Reaction Sequence: 
##STR2## 
Initially, the methyl groups of the 4-substituted ortho-xylene (compounds 
1) are directly halogenated. Disubstitution of halo on each of these 
groups is found to be most facile when bromo is the desired halo 
substituent. The reaction occurs readily using N-bromosuccinimide as the 
brominating agent. See for example, Djerassi, Chem. Revs., 43, 271 (1948). 
Compound 2, the 4-substituted-.alpha.,.alpha.,.beta.,.beta. 
-tetrabromo-o-xylene, is next dehalogenated in a manner known for the 
hydrolysis of gem-dihalides in the presence of a suitable catalyst. The 
catalysts include, for example, calcium carbonate, sulfuric acid, 
morpholine and various silver salts. Typically a mixture of acetic acid, 
compound 2 and silver acetate is heated, resulting in dehalogenating 
compound 2 to compound 3 which is readily converted to compound 4 
typically with base such as sodium bicarbonate. The 
4-substituted-1,2-phthalic aldehyde intermediate (4) is next converted to 
the 6-substituted-2,3-dihydroxy-1,4-naphthoquinone compound 5 by reaction 
with glyoxal (OHCCHO). This reaction is reported in some detail in the 
aforesaid Weygand Patenshrift No. 859,008, which is incorporated herein by 
reference. Generally the reaction is carried out in an aqueous base at a 
pH of between 8 and 12 and at temperatures of 10.degree. to 80.degree. C. 
The bases which are employed include alkali metal carbonates, bicarbonates 
and hydroxides, tertiary amines and the like. 
The compounds of Formula (I) wherein R.sup.1 alkyl of 1-5 carbon atoms 
prepared by esterifying the 2,3-dihydroxy compound using methods known in 
the art. For example, with acyl anhydride or chloride in pyridine solution 
or in an inert solvent such as tetrahydrofuran containing a tertiary base 
such as pyridine or triethylamine or with acyl anhydride in the presence 
of an acid catalyst such as zinc chloride, sulfuric acid or 70% perchloric 
acid. Suitable acyl anhydrides and acyl chlorides include, for example, 
acetic anhydride, propionic anhydride, butyl anhydride, valeryl anhydride, 
caproyl anhydride, acetyl chloride, propionyl chloride, butyryl chloride, 
valeroyl chloride, caproyl chloride and the like. 
The compounds of Formula (I) wherein R is defined as in Reaction Sequence 1 
are also prepared by oxidizing 6-substituted-2-hydroxy-1,4-naphthoquinone 
or 7-substituted-2-hydroxy-1,4-naphthoquinone according to Reaction 
Sequence 2. 
##STR3## 
Generally the precursors 7 are known compounds. See, for example, J. Am. 
Chem. Soc. 71, 3615-17 (1949) and J. Am. Chem. Soc. 75, 2910-15 (1953). 
The oxidation is suitably carried out by employing methods known in the 
art such as basic hydrogen peroxide, peracids, e.g., peracetic acid, 
m-chloroperbenzoic acid, potassium ferricyanide aqueous in alkaline 
solution, and the like, preferably basic hydrogen peroxide. 
In the specification and claims the term "C.sub.1 to C.sub.18 linear or 
branched alkoxy" is intended to mean alkoxy groups containing 1 to 18 
carbon atoms including straight chain groups, branched chain groups and 
straight or branched chain groups optionally having an optionally 
substituted phenyl group. Illustrative of such groups are, for example, 
methoxy, ethoxy, n-propoxy, isopropoxy, n-hexoxy, 2-methylpentoxy, 
n-octoxy, benzyloxy, 4-methyl-benzyloxy, 4-chlorobenzyloxy and the like. 
The term "halo" refers to the radicals fluoro, chloro, bromo and iodo.

For Preparations 1 and 2 and Examples 1 and 2, reference should be made to 
the Reaction Sequence 1. 
PREATION 1 
A. 4-Chloro-.alpha.,.alpha.,.beta.,.beta.-tetrabromo-o-xylene 
A mixture of 4-chloro-o-xylene (1: 14.0 g, 0.1 mol) and freshly 
recrystallized N-bromosuccinimide (80 g, 0.45 mol) in carbon tetrachloride 
(1 L) is irradiated for 21/2 hours (hr) with a 250 watt tungsten infrared 
lamp positioned so that the solvent refluxed gently. The solid material is 
then removed by filtration, the filtrate is concentrated in vacuo and the 
crystalline residue is recrystallized from isopropanol giving 34 g (75%) 
of 4-chloro-.alpha.,.alpha.,.beta.,.beta..alpha. -tetrabromo-o-xylene (2), 
melting point (mp) 108.degree.-111.degree. C. [Bull. Soc. Chim., 2966 
(1966), mp 114.degree. ]. 
B. In like manner, but substituting 
o-xylene 
4-bromo-o-xylene 
4-fluoro-o-xylene 
4-cyano-o-xylene 
4-methoxy-o-xylene 
4-ethoxy-o-xylene 
4-butoxy-o-xylene 
4-hexyloxy-o-xylene and 
4-undecyloxy-o-xylene for 4-chloro-o-xylene, the following compounds are 
obtained: 
.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene, 
4-bromo-.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene, 
4-fluoro-.alpha., .alpha., .beta., .beta.-tetrabromo-o-xylene, 
4-cyano-.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene, 
4-methoxy-.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene, 
4-ethoxy-.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene, 
4-butoxy-.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene, 
4-hexyloxy-.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene, and 
4-undecyloxy-.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene. 
PREATION 2 
A. 4-Chloro-1,2-phthalic aldehyde 
A mixture of 2 (22.8 g, 0.05 mol), silver acetate (36.6 g, 0.22 mol) and 
glacial acetic acid (500 ml) is heated under reflux for 11/2hr. The silver 
salts are filtered off, washed with chloroform and the combined filtrates 
concentrated to dryness in vacuo. The last traces of acetic acid are 
removed from the residue by evaporation with toluene. The resultant 
semicrystalline material 3 is dissolved in dioxane (500 ml) and a solution 
of sodium carbonate (53 g) in water (500 ml) is added. This mixture is 
shaken vigorously at 22.degree. for 20 minutes, saturated with sodium 
chloride and then extracted with ethyl acetate (2.times.500 ml). The 
combined organic extracts are washed with brine (2.times.400 ml), dried 
with MgSO.sub.4 and concentrated in vacuo giving 6.0 g (72%) of almost 
pure 4-chloro-1,2-phthalic aldehyde. Sublimation at 75.degree. and 0.05 mm 
Hg affords 5.4 g of 4, with mp 72.degree.-76.degree.. 
B. In like manner, but substituting the compounds prepared in Part B of 
Example I for 4-chloro.alpha.,.alpha.,.beta.,.beta. -tetrabromo-o-xylene, 
the following compounds are prepared: 
1,2-phthalic aldehyde, 
4-bromo-1,2-phthalic aldehyde, 
4-fluoro-1,2-phthalic aldehyde, 
4-cyano-1,2-phthalic aldehyde, 
4-methoxy-1,2-phthalic aldehyde, 
4-ethoxy-1,2-phthalic aldehyde, 
4-butoxy-1,2-phathalic aldehyde, 
4-hexyloxy-1,2-phthalic aldehyde, and 
4-undecyloxy-1,2-phthalic aldehyde. 
EXAMPLE 1 
A. 6-Chloro-2,3-dihydroxy-1,4-naphthoquinone 
A solution of sodium carbonate (12.3 g) in water (290 ml) is added at room 
temperature to a vigorously stirred solution of 4-chloro-1,2-phthalic 
aldehyde (4.88 g, 29 mmol) in an oxygen atmosphere followed immediately by 
the addition, over a five minute period, of a solution of glyoxal 
bisulfite (16.4 g, 58 mmol) and potassium cyanide (1.88 g, 29 mmol) in 
water (290 ml). The reaction mixture is stirred in the oxygen atmosphere 
for a further 5 minutes. It is then treated with 6 N hydrochloric acid (50 
ml), cooled in an ice-salt bath and further diluted with water (500 ml). 
The crystalline product is collected by filtration, washed with water, 
dried and recrystallized from water:methanol (2:1) giving 3.56 g (55%) of 
6-chloro-2,3-dihydroxy-1,4-naphthoquinone, mp 228.degree.-229.degree.. 
B. In like manner, by substituting the other 1,2-phthalic aldehydes of Part 
B, Preparation 2 for 4-chloro-1,2-phthalic aldehyde, the following 
compounds are obtained: 
2,3-dihydroxy-1,4-naphthoquinone, 
6-bromo-2,3-dihydroxy-1,4-naphthoquinone, 
6-fluoro-2,3-dihydroxy-1,4-naphthoquinone, 
6-cyano-2,3-dihydroxy-1,4-naphthoquinone, 
6-methoxy-2,3-dihydroxy-1,4-naphthoquinone, 
6-ethoxy-2,3-dihydroxy-1,4-naphthoquinone, 
6-butoxy-2,3-dihydroxy-1,4-naphthoquinone, 
6-hexyloxy-2,3-dihydroxy-1,4naphthoquinone, and 
6-undecyloxy-2,3-dihydroxy-1,4-naphthoquinone. 
EXAMPLE 2 
Since known effective anti-psoriasis agents inhibit epidermal cell 
proliferation, an animal assay using young male rats has been developed 
wherein the test agent in an appropriate carrier is applied to the skin of 
one flank of the test animal while the carrier alone is applied to the 
other flank, i.e., the control. At a suitable time interval after one or 
more applications of the composition, the skin is removed from the animal 
and skin plugs taken from both the treated and the control areas are 
incubated in vitro with tritium labelec thymidine (a precursor of DNA 
synthesis). A comparative measure of the amount of radio-labeled thymidine 
incorporated into the DNA of plugs from the treated and control flanks 
gives a measure of the degree of inhibition of DNA synthesis and hence 
epidermal cell proliferation which has occurred in response to the 
treatment. 
Compositions illustrative of the compositions of the present invention are 
tested in the rat in the method disclosed above. The tests are 
specifically carried out as follows: 
Male albino rats, 21-22 days old are shaved on the back and both flanks 
with electric clippers twenty-four hours prior to testing. A suitable 
2,3-diacyloxy-6substituted-11,4,-naphthoquinone is dissolved in a mixture 
of ethanol (EtOH), acetone, dimethyl sulfoxide (DMSO) or mixture of DMSO 
and EtOH. Solutions (0.10 ml) containing the test agent, are applied to 
the right flank of the animals and the carrier alone (0.10 ml) is applied 
to the left flank. The area covered is approximately 10 sq. cm. 
Applications are made seven hours apart on days 1, 2 and 3. On day 4 the 
animals are sacrificed by carbon dioxide asphyxiation, and the full 
thickness skin from the back and both flanks is removed. Subcutaneous fat 
and muscle are scraped away and plugs consisting of epidermis and dermis, 
6 mm. in diameter are punched out, five from the control flank and five 
from the treated flank. These are incubated at 37.degree. C. individually 
floating on 3 ml of Dulbecco's Modified Eagle Medium containing tritiated 
thymidine (10 microcuries/milliliter). After two hours incubation of plugs 
are frozen, thawed, blotted dry, rinsed 3 times in 30% aqueous acetic acid 
and once in absolute ethanol to remove unincorported tritiated thymidine. 
The washed plugs are digested in NCS solubilizer for liquid scintillation 
counting in order to determine the amount of tritiated thymidine 
incorporated into the DNA. The inhibitory effect of the treatment is 
determined by comparing the amount of radioactivity incorporated into 
plugs from the treated side with that incorporated into plugs from the 
control flank. For each test at least two animals are used. The data are 
recorded for each animal as the ratio of mean radioactivity is the treated 
side to the mean radioactivity of the control side (X100). 
The amount of tritiated thymidine incorporated is primarily due to 
epidermal cells, and hence the amount of radioactivity in these tests is 
directly related to the number of cells (epidermal) engaged in 
proliferation (DNA synthesis) at the moment of sacrifice. As noted 
earlier, epidermal cell hyper-proliferation is symptomatic of psoriasis. 
The compounds useful in the composition of this invention show inhibitory 
activity against epidermal cell proliferation and as a result are 
anti-psoriatic agents. 
EXAMPLE 3 
A solution of 1.2 gm 6- chloro-2-hydroxy-1,4-naphthoquinone (or 7-chloro or 
mixture thereof) and 0.48 g sodium bicarbonate in 58 ml of water is cooled 
to 5.degree. C. and 2.3 ml of 30% hydrogen peroxide is added in one 
portion. The mixture is then stirred at 22.degree. C. for 16 hours where 
the red crystalline product (0.24 g) is removed by filtration and 
crystallized from water:methanol (2:1) giving the 
6-chloro-2,3-dihydroxy-1,4-naphthoquinone, m.p. 228.degree.-229.degree. C. 
EXAMPLE 4 
A. Concentrated sulfuric acid (0.1 ml) is added to a suspension of 1 g of 
6-chloro-2,3-dihydroxy-1,4-naphthoquinone in 5 ml of acetic anhydride and 
the mixture is gently shaken at 22.degree. C. until a clear, pale yellow 
solution is obtained (less than 5 minutes). After a further 5 minutes at 
22.degree. C. the solution is poured into 250 ml of saturated sodium 
bicarbonate solution and the yellow crystalline material is collected by 
filtration, washed well with water and dried in vaccuo giving 1.05 g of a 
product having a melting point of 109.degree.-110.degree. C. 
Recrystallization from ethyl acetate/hexane (1:2) gives 2,3-diacetoxy 
6chloro-1,4-naphthoquinone, m.p. 110.degree.-111.degree. C. 
B. In like manner, but substituting the compounds of Example 1, Part B for 
6-chloro-2,3-dihydroxy-1,4-naphthoquinone 
2,3-diacetoxy-1,4-naphthoquinone, 
2,3-diacetoxy-6- bromo-1,4-naphthoquinone, 
2,3-diacetoxy-6- fluoro-1,4-naphthoquinone, 
2,3-diacetoxy-6- cyano-1,4-naphthoquinone, 
2,3-diacetoxy-6- methoxy-1,4-naphthoquinone, 
2,3-diacetoxy-6- ethoxy-1,4-naphthoquinone, 
2,3-diacetoxy-6-butoxy-1,4-naphthoquinone, 
2,3-diacetoxy-6- hexyloxy-1,4-naphthoquinone, and 
2,3-diacetoxy-6- undecyloxy-1,4-naphthoquinone. 
EXAMPLE 5 
Concentrated sulfuric acid (0.1 ml) is added to a suspension of 1 g of 6- 
chloro-2,3-dihydroxy-1,4-naphthoquinone in 5 ml of caproic anhydride and 
the mixture is gently shaken at 22.degree. C. until a clear, pale yellow 
solution is obtained (less than 5 minutes). After a further 10 minutes at 
22.degree. C. the solution is poured into 250 ml of saturated sodium 
bicarbonate solution. The organic layer is extracted with ethylacetate 
which is then evaporated from the solution. The resulting product 
(2,3-dicaproyloxy-6-chloro-1,4-naphthoquinone) is purified by thin layer 
chromatography using an elution mixture of 9 parts hexane and 1 part ether 
(volume/volume) which results in an RF value of 0.62. 
EXAMPLE 6 
By following in principle the appropriate procedures of Example 4, Parts A 
and B or Example 5, but substituting other acyl anhydrides for acetic 
anhydride and caproic anhydride, such as propionic anhydride, butyric 
anhydride or valeric anhydride, the following compounds are obtained: 
6-chloro-2,3-dipropionyloxy-1,4-naphthoquinone, 
6-chloro-2,3-dibutyroxy-1,4-naphthoquinone, 
6-chloro-2,3-divaleryloxy-1,4-naphthoquinone, 
6-bromo-2,3-dipropionyloxy-1,4-naphthoquinone, 
6-fluoro-2,3-dipropionyloxy-1,4-naphthoquinone, 
6-cyano-2,3-dipropionyloxy-1,4-naphthoquinone, 
6-methoxy-2,3-dipropionyloxy-1,4-naphthoquinone, 
6-hexyloxy-2,3-dipropionyloxy-1,4-naphthoquinone, and the like.