WO1992014439A1 - Agent stimulant la croissance des cheveux - Google Patents

Agent stimulant la croissance des cheveux Download PDF

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Publication number
WO1992014439A1
WO1992014439A1 PCT/JP1992/000154 JP9200154W WO9214439A1 WO 1992014439 A1 WO1992014439 A1 WO 1992014439A1 JP 9200154 W JP9200154 W JP 9200154W WO 9214439 A1 WO9214439 A1 WO 9214439A1
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group
dimethyl
mixture
benzopyran
nitro
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PCT/JP1992/000154
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English (en)
Japanese (ja)
Inventor
Hiroshi Koga
Hiroyuki Nabata
Hiromichi Nishina
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Chugai Seiyaku Kabushiki Kaisha
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Priority to JP50508292A priority Critical patent/JP3255411B2/ja
Publication of WO1992014439A1 publication Critical patent/WO1992014439A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention relates to a hair growth promoter comprising one or more benzopyran derivatives or pharmaceutically acceptable salts thereof having an excellent hair growth promoting effect.
  • the present invention is used in the field of pharmaceuticals or cosmetics for alopecia areata, alopecia areata, postpartum alopecia and androgenetic alopecia due to anticancer agents. Furthermore, it is also used as a hair growth promoting agent in fields requiring hair and fur, such as sheep and mink. Background art
  • Alopecia is roughly divided into congenital alopecia and acquired alopecia. Of these, acquired alopecia can be broadly classified into those with scars and those without skin lesions. In addition, scars, alopecia without skin lesions, alopecia due to drugs, traumatic alopecia, alopecia associated with nutritional disorders and metabolic disorders, alopecia associated with abnormal endocrine disorders, alopecia associated with abnormal endocrine disorders, hair loss after hyperthermia (hair loss after high fever and postpartum hair loss) Male pattern baldness 7 Alopecia areata can be divided into 7 categories. Most of the conventional hair restorer or hair restorer only targets male pattern baldness.
  • the physiological characteristics of androgenetic alopecia are as follows: first, the testosterone, the main body of the male hormone, is a more potent male hormone, 5 or— It is converted to dihydrodote testosterone (hereinafter referred to as 5 or -DH).
  • 5 or -DH dihydrodote testosterone
  • This 5 or DHT binds to an intracellular receptor and acts on the nucleus to suppress the division of hair matrix cells in the hair bulb, impede hair growth, and promote hair removal and hair loss. I have.
  • antimaleformin agents having an inhibitory effect on reductase or an inhibitory effect on binding of 5 ⁇ -DH ⁇ to a receptor have been used for male pattern baldness.
  • antiandrogens examples include oxendronone, chlormadinone diacid, .11 ⁇ -hydroxyprogesterone, 41-androthone-3-one-one 17/9 carboxylic acid, and cyproate acetate. and so on.
  • all of these antiandrogens are derivatives of steroid hormones, and when administered to living organisms, themselves or their metabolites show hormonal production; In many cases, serious side effects were observed, and there was a problem in terms of safety G. From this point, flavonoids that do not have a steroid skeleton ⁇ -Reductase inhibitors have also been found, but they are all indicated only for androgenetic alopecia and only stop the progression of alopecia by that mechanism.
  • ⁇ ⁇ carpronium chloride
  • the antihypertensive agent diazoxide has been shown to have a hair growth promoting effect.
  • the effect of promoting hair growth is very weak when used in a small amount, and there is a problem that when used in a large amount to achieve the effect, side effects such as hyperglycemia occur.
  • Minoxidil which also acts as a blood pressure lowering agent, has been shown to have a hair growth promoting effect.
  • Minoxidil unlike conventional drugs, is a drug that directly has hair follicle stimulating action, in addition to the vasodilatory action of ⁇ ⁇ ⁇ ⁇ . Therefore, unlike the above-mentioned anti-androgen, it is effective not only for male pattern baldness but also for alopecia areata.
  • diazoxide has a problem of hyperglycemia, and minoxidil will not be activated unless sulfated, and will not have a sufficient hair growth promoting effect. Therefore, it has been desired to develop a drug that does not have the side effect of hyperglycemia, does not need to be activated by receiving internal metabolism, has a stronger hair growth promoting effect, and has low transdermal absorption.
  • the International Application Publication No. WO 90/13464 (International filing date May 15, 1990; International publication date Jan. 29, 1990) contains Compounds, including the hen '/ pyran derivatives used in the invention, are described. According to the above specification, the compound has a smooth muscle relaxing action, which causes respiratory disorders, high blood pressure, gastrointestinal spasm, and cardiovascular Although it is described that it is effective in treating disorders and epilepsy, it does not mention or suggest that it has a hair growth promoting effect and is effective as a hair growth promoting agent.
  • FIGS. 1, 3 and 5 to 19 are graphs showing the hair growth effect of mice when a benzovirane derivative or the like is applied and applied.
  • FIGs 2 and 4 are photographs showing the hair growth of mice 14 days after the start of the test.
  • the hair growth promoter of the present invention is characterized by containing one or more benzopyran derivatives represented by the following general formula (I) or a pharmaceutically acceptable salt thereof.
  • Y is - NR B R ,, one OR 10 or - the SRH, wherein R 8 and R 9 are identical or different and represent a hydrogen atom, a hydroxyl group, a lower alkoxy group, Shiano group, substituted Moyoi
  • Indicates a ring! ? ⁇ And! ⁇ Also represents a hydrogen atom, a lower alkyl group or an aryl group;
  • R. represents a hydrogen atom, a lower alkyl group or an aryl group, or directly bonds with R 2 to form a single bond:
  • R 2 and R 3 are the same or different and each represent a hydrogen atom or a hydroxyl group, or R 0 and R 2 are directly bonded to form a single bond.
  • R 4 and R 5 are the same or different and are a hydrogen atom or a lower alkyl group which may have a substituent. Or together form a polymethylene group;
  • R e and R 7 may be the same or different and are a hydrogen atom, a lower alkyl group, a lower haloalkyl group, a halogen atom, a lower alkoxy group, a lower haloalkoxy group, an amino group, an acylamino group, a nitro group, a cyano group, an ester
  • the lower alkyl group means an alkyl group having 1 to 6 carbon atoms, and preferably an alkyl group having 1 to 4 carbon atoms.
  • lower alkyl groups examples include methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl and the like. .
  • An aryl group means a monovalent substituent obtained by removing one hydrogen atom from an aromatic hydrocarbon, and specifically, a phenyl group, a tolyl group, a xylyl group, a biphenyl group, a naphthyl group, an anthryl group And a phenanthryl group. Particularly preferred is a phenyl group.
  • the carbon atom on the ring of the aryl group may be substituted by one or more groups such as a halogen atom, a lower alkyl group, an amino group, a nitro group and a trifluoromethyl group.
  • the heteroaryl group is an aryl group having a hetero atom.
  • a viridyl group examples include a viridyl group, a bilimidyl group, a thiazolyl group, an oxazolyl group, an imidazolyl group, a thiadiazol group, and a tetrazolyl group. Further, these rings may have a substituent.
  • the lower alkoxy group means an alkoxy group having 1 to 6 carbon atoms, preferably an alkoxy group having 1 to 4 carbon atoms. Examples of such lower alkoxy groups are-. Methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy and the like. No.
  • the halogen atom means chlorine, bromine, fluorine or iodine, and chlorine is particularly preferred.
  • Cycloalkyl groups and those having 3 to 8 carbon atoms are preferable, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.
  • Examples of the nitrogen-containing heterocyclic ring include an aziridinyl group, an azetidur group, a pyrrolidinyl group, a biperidinyl group, a piperazyl group, and a morpholino group.
  • substituents examples include a halogen atom, a lower alkyl group, a lower alkoxy group, an amino group, a nitro group, a lower haloalkyl group, a lower haloalkoxy group, and a cyano group.
  • the compound represented by the general formula (I) can be produced, for example, as follows.
  • R 4 , R S , R b and R 7 have the same meaning as described above;
  • R 12 represents a hydrogen atom, a lower alkyl group or an aryl group.
  • X and Y have the same meaning as described above;
  • L represents a halogen atom, —OR 13 , —S (0)) RH, or a leaving group such as RH, wherein R 13 and R 14 represent a hydrogen atom A lower alkyl group or an aryl group, and n represents an integer of 0 to 2)
  • Examples of the base used herein include sodium hydride, sodium alkoxide, potassium alkoxide, alkyl lithium, potassium carbonate, sodium carbonate., Sodium hydroxide, sodium hydroxide and the like.
  • the compound of the present invention represented by the general formula (I) is a compound represented by the general formula (D),
  • the compound of the general formula (I) may also have the general formula (V)
  • the reduction reaction is in an inert solvent, the reducing agent for example, Na BH 4, KBH 4, L i, N a BH 3 CK ⁇ L i A 1 or to apply a borohydride or a metal hydride H 4, etc., or It can be carried out by catalytic reduction using palladium carbon or Raney nickel.
  • the dehydration reaction is carried out in an inert solvent using an acid such as p-toluenesulfonic acid or hydrogen chloride, or in the presence of a base in the presence of a base such as an acid halide such as para-toluenesulfuric acid or acetic acid or acetic anhydride. This is performed by using an acid anhydride.
  • Examples of the base used here include organic bases such as pyridine and triethylamine, or sodium hydride, sodium alkoxide, potassium alkoxide, alkyl lithium, potassium carbonate, sodium carbonate, hydroxide hydroxide, and sodium hydroxide. Thorium and the like.
  • the compound (I) of the present invention can also be obtained by applying the specific production methods described in the examples.
  • the blending amount of the benzovirane derivative is about 0.001 to 10% by weight (hereinafter,% by weight is simply referred to as%) in the hair growth promoter of the present invention. If it is less than 0.01%, the effect of promoting hair growth may not be exhibited. Also, the greater the blending amount is, the greater the hair-growing effect is, but it is preferably 10% or less in consideration of the appearance of side effects when used in large amounts. More preferably, it is 0.01 to 5%.
  • the hair growth-promoting agents according to the present invention include bactericides such as salicylic acid, resorcin, and hexaclofen which are generally used in hair restorers, nicotinic acid, vitamin E, vitamin A, pantothenic acid , Biotin, other vitamins, fatty acids, amino acids, menthol, lower alcohols such as ethanol, higher alcohols such as cetanol, polyhydric alcohols such as polyethylene glycol and propylene glycol, and hydroxypropyl cellulose.
  • bactericides such as salicylic acid, resorcin, and hexaclofen which are generally used in hair restorers, nicotinic acid, vitamin E, vitamin A, pantothenic acid , Biotin, other vitamins, fatty acids, amino acids, menthol, lower alcohols such as ethanol, higher alcohols such as cetanol, polyhydric alcohols such as polyethylene glycol and propylene glycol, and hydroxypropyl cellulose.
  • the hair growth-promoting agent according to the present invention can be applied to any externally used dosage form such as liquid, emulsion, ointment, cream, gel, aerosol and the like, and can also be applied to shampoo rinse and the like. .
  • Production Examples 1 to 42 describe the method for producing the benzoviran derivatives described in Table 1 below. To explain,
  • Cis-1-N-methyl-6-cyano-3,4-dihydro ⁇ -3-hydroxy-1 2: 2-dimethyl-1-2-benzovirane-14-carbothioamide;
  • 1-methyl-6-cyano 3-heptadroxy-1,2,2-dimethyl-2 1,4-benzoviran-1,4-carbothioamide 1.4 g, a mixture of tetrahydrofuran 15 / ⁇ and methanol 15 Under stirring at 0 ° C., 0.23 g of sodium borohydride (NaBH 4 ) was added, and the mixture was stirred at 110 ° C. for 2 hours and then at room temperature for 2 hours. The reaction solution was distilled off under reduced pressure, and ice water was added to make it acidic with acetic acid. Extracted with chill. The organic layers were combined, dried over Na 2 SO 4 and retained.
  • NaBH 4 sodium borohydride
  • N-methyl-6-cyano 3,4-dihydro 3-hydroxy-1,2,2-tyl-2H-1-benzopyran-1-4-ruvothioamide 0.44 g, NO, 'Latruens Rufonic acid monohydrate
  • a mixture of 0.07 g and toluene 30 ⁇ was heated under reflux for 10 hours.
  • the solvent was distilled off, and the residue was purified by silica gel chromatography (developing solution CH 2 C 12 ) to give a melting point of 13 9 to: I 41
  • 0.18 g of N-methyl-6-cyano-2: 2-dimethyl-2H-1-benzopyran-41-carbothioamide represented by the following formula was obtained.
  • 6-cyan-1,3-dihydro-1,2-dimethyl-2H-1-benzopyran-13-one 0.5 g, phenyl sothiocyanate 0.37 g and dried N, N-dimethylformamide 5 «£
  • To the mixture was added 0.31 g of potassium tert-butoxide with stirring under ice cooling, and the mixture was stirred under ice cooling for 5 hours. Ice water was added, the mixture was acidified with acetic acid, and extracted with ether. The ether layer was washed with water and dried over sodium sulfate, and the ether was distilled off.
  • the residue is purified by silica gel chromatography (developing solution CH 2 C 12 ), and has a melting point of 30 (TC or more (softening around 10 and solidifying after about 10) and represented by the following formula: N-phenyl-6-cyano-3-H There was obtained 0.4 g of droxy-1,2-dimethyl-2H-1-benzopyran-4-potassium ribothioamide.
  • the organic layer was washed with a 2 N aqueous solution of potassium carbonate and a saturated saline solution, and dried over magnesium sulfate.
  • NMB (CDCI 3 ): 1.6 (6H, s), 3.1 (3H, d), 5.9- 6.2 (1H, bs), 6.1 (lH, s), 6.9 (lH, d),
  • 6-nitro-1,2-dimethyl-1,2H-1-benzopyran-1,4-butyric acid 1.00 g, 2,2,2-trifluoroethylamine 0.44 g, 2,2'-dipyridyl disulfide 0.97 g, 1.16 g of triphenylphosphine and 2 ° C of dichloromethane were stirred at room temperature for 3 hours.
  • N-Methyl-3,4-dihydro-1-3-hydroxy-6-Trifluoromethyl-1,2-dimethyl-2H-1 Benzovirane 4-Carbothioamide 0.17 g, chloride P-Toluenesulfonyl 0.21 g and pyridine 1 0 ⁇ mixture after 4 hours heating under reflux, and dried over extracted magnesium sulfate with dichloromethane added 2 N hydrochloric acid, Li force gel column chromatography (CH Z C1 2: Methanol 1 0 0: 1) purification And then recrystallized with a mixture of getyl ether and n-hexane, and has a melting point of 146-150, and is represented by the following formula: N-methyl-6-trifluoromethyl-2> 2-dimethyl One 2H-1-benzopyran-14-carbamide 44 was obtained.
  • the least polar component is further recrystallized with a mixture of getyl ether and n-hexane, and has a melting point of 9-97, 6-nitro-1,2,2-dimethyl-2. 0.15 g of H—1—benzopyran was obtained. NMR (CDC1 3): 1.4 ( 3H, t), 1.5 (6H, s), 4.35 (2H, q), 6.8 (lH, s), 6.85 (lH, d), 8.05 (lH, dd), 9.0 ( lH, d).
  • N-cyano-6-nitro-2 represented by the following formula having a melting point of 91-93'C.
  • NMB (CDC1 3): 1.5 ( 3H, t), 1.6 (6H, s) 5 4.6 (2H s q) 5 6.5 (lH s s), 6.85-7.1 (1H, m): 8.0-8.3 (2H, m ).
  • the most polar component is further recrystallized with a mixture of ethyl acetate and n-hexane, and has a melting point of 205-207, and is represented by the following formula, N-cyano-6-nitro-2 ⁇ 0.08 g of 2-dimethyl- 1 2 H- 1-benzovirane-41-amidine was obtained.
  • NMiKCDCls 0.5-1.0 (4H, m), 1.5 (6H, s), 2.7-3.2 (lH, m), 5.9 (lH, s), 6.8 (1 ⁇ , d), 6.9-7.4 (lH, m) , 7.7 (lH, d), 8.0 (lH, dd).
  • N-Methyl-6-nitro-2,2-dimethyl-2H-1 Benzopyran-14-carbamide 0.53 g, sodium borohydride 0.38 g, tetrahydrofuran 53 ⁇ 4 and methyl alcohol 5ffl2 After stirring at room temperature for 20 minutes, 2N hydrochloric acid was added, extracted with dichloromethane, dried over magnesium sulfate, recrystallized with ethyl acetate and n-hexane, and melted with the following formula having a melting point of 16 1-16 2 'C. There was obtained 0.42 g of the indicated N-methyl-3: 4-dihydro-6-nitro-2,2-dimethyl-2H-1-benzopyran-14-l-carbamide.
  • N-sulfamoyl-N ', N'-dimethyl-6-nitro-1,2,2-dimethyl-2H-1,1-benzopyran-41-amidine represented by the following formula having a melting point of 2 1 2 -2 1 0.17 g was obtained.
  • Nitrogen was added to a mixture of 4,1.5 g of 3,4-dihydro-1,2-dimethyl-6-two-row 2 H—1-benzozoranan—3-one and 41.5 g of dry N, N-dimethylformamide 500 » ⁇ .
  • 8.2 g of sodium hydride (60%) was gradually added while stirring under ice-cooling with stirring, and after stirring for 50 minutes, 33.5 g of carbonyldiimidazole was added. After stirring for 1 hour, 11.2 g of ammonium chloride and triethylamine were added. After adding 29ffl £, the mixture was stirred for 5 to 12 hours, and then stirred at room temperature for 14 hours. Ice water was added, and the mixture was washed with water.
  • the aqueous layer was acidified with hydrochloric acid and extracted with a mixed solvent of ethyl ethyl ether and ether.
  • NMB (CDC1 3 one CD 3 0D): 1.50 (6H , s), 7.00 (lH, d), 7.97 (lH, dd), 8.27 (lH, d).
  • reaction solution was distilled under reduced pressure, water was added, and the mixture was extracted with a mixed solvent of ethyl acetate and ether. The organic layer is washed with water and dried, and the solvent is distilled off to obtain 24 g of 3,4-dihydro-13-hydroxy-1,2,2-dimethyl-16-nitro-12H-1-1-benzovirane-14-carbamide. Obtained.
  • 51.5 g of rosetoluenesulfuric acid mouth light and viridine 400 ⁇ were added thereto, and the mixture was heated under reflux for 3 hours, and then the solvent was distilled off. Ice water was added to the residue, the mixture was acidified with hydrochloric acid, and the precipitated crystals were collected by filtration, washed with water and dried.
  • Trimethyl-1-acetamide-1 H-2 Benzopyran-1 Carboamide A mixture of N, 2,2-trimethyl-1-6-nitro-1H-2H-1 benzopyran-14-carboamide 1.55 g, stannous chloride 3.84 g and dry ethanol 30 ⁇ is heated to reflux for 4 hours did. After the solvent was distilled off, acetic anhydride 15 was added, and the mixture was stirred at room temperature for 17 hours. The reaction solution was distilled off under reduced pressure, 2N-hydrochloric acid was added, and the mixture was extracted with a mixed solvent of ethyl sulphate and polyester.
  • N, 2,2-trimethyl-6-acetylamide 7-2-trough 2H-1-benzopyran-1 4-carboamide 0.50 g, ethanol 15 5 «£ and 2N-sodium hydroxide was added at room temperature for 3 hours. Stirred for hours. Saturated saline was added and extracted with ether. The organic layer is washed with a saturated saline solution, dried, and the solvent is distilled off. N, 2,2-trimethyl-6-amino-17-nitro represented by the following formula having a melting point of 202-205 • C — 0.40 g of —2H-11-benzovirane-41-carbamide was obtained.
  • 0.08 g of sodium hydride (60%) under ice-cooled stirring, and the mixture was stirred at room temperature for 12 hours, and then stirred at 40 to 30 minutes. Ice water was added and extracted with methylene chloride.
  • N-cyano N represented by the following formula with a melting point of 185-187 N'-Dimethyl 6-nitrosubilo [2H-1-benzovirane-1,2'-cyclobutane: 141-amidine 0.06 g was obtained.
  • NMB (CDC1 3 -CD 3 0D) : 1,40-2.20 (10H, m), 2.95 (3H, d), 5.95 (lH, s), 6.85 (lH, d): 7.75 (lH, d), 8.00 (lH, dd)
  • 6-Nitrosviro [2H-1-benzovirane-1,2'-cyclohexane]
  • carboediimidazole 365 mg under ice-cooling and stirring.
  • 2-cyanoethylamine 0.37 ⁇ in tetrahydrofuran was added, and the mixture was stirred under ice cooling for 45 minutes.
  • An aqueous solution of potassium carbonate was added, and the mixture was extracted with methylene chloride. The organic layer is washed with water, dried, and the solvent is distilled off.
  • N- (2-cyanoethyl) -1-6-nitro-2,2-dimethyl-2H-1 -benzopyran-14-carbamide 0.40 g, Lawesson's reagent 0.28 g and benzene 2 ⁇ was added for 1 hour After heating and refluxing for 1 minute, the product was purified by silica gel gel chromatography (CHzCHz), recrystallized with a mixture of getyl ether and n-hexane, and expressed by the following formula with a melting point of 11.6-118'C.
  • N- (2-cyanoethyl) -6 6 1,2,2-dimethyl-2H-1, 1-benzoviran-41-carbothioamide 0.24 g was obtained.
  • mice 7-week-old CS HZH e N mice (males) were purchased and preliminarily reared for 2 weeks. After that, 10 mice were divided into groups, and the backs of the mice were shaved twice with a clipper and a sliver twice for 3 days before the application of the drug. After one day, an ethanol solution (0.0003 to 1.%) of the compound of the present invention was applied once a day at a dose of 100 / animal in a pit, and another group was used as a control.
  • the hair growth-promoting agent of the present invention having a benzopyran derivative shows a considerably higher hair growth-promoting effect than minoxidil. Therefore, the hair growth-promoting agent of the present invention is useful for the treatment and prevention of alopecia areata, postpartum alopecia, and alopecia caused by anticancer drugs, as well as male pattern baldness.

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Abstract

L'invention se rapporte à un agent stimulant la croissance des cheveux, qui comprend un dérivé de benzopyranne représenté par la formule générale (I) ou au moins un sel pharmaceutiquement acceptable de ce dérivé. Dans le formule (I), X représente =O, =S, =N-Z (Z représentant alkyle inférieur, etc.) ou =CHNO2; Y représente amino, alcoxy, alkylthio, etc. substitué; et R1 à R7 représentent chacun hydrogène, alkyle inférieur, etc. Cet agent possède une excellente propriété de stimulation de la croissance des cheveux, non accompagnée d'effets secondaires, et il peut par conséquent être utilisé comme médicament contre l'alopécie due à diverses causes et comme cosmétique.
PCT/JP1992/000154 1991-02-18 1992-02-17 Agent stimulant la croissance des cheveux WO1992014439A1 (fr)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5470861A (en) * 1994-08-04 1995-11-28 Hoffmann-La Roche Inc. Method of promoting hair growth
US5646310A (en) * 1993-04-23 1997-07-08 Chugai Seiyaku Kabushiki Kaisha N-(2-cyanoethyl)-6-fluoroalkyl-2h-1-benzopyran derivatives
WO2001072727A1 (fr) * 2000-03-27 2001-10-04 Shiseido Co., Ltd. Toniques capillaires
JPWO2005027904A1 (ja) * 2003-09-22 2006-11-24 日本新薬株式会社 育毛剤

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JPS6033433B2 (ja) * 1978-11-08 1985-08-02 フアイザ−・インコ−ポレ−テツド ハロゲン置換ベンゾピラン−４−カルボン酸およびその誘導体
JPS63303977A (ja) * 1987-05-16 1988-12-12 サンド・アクチエンゲゼルシャフト 新規ベンゾ［ｂ］ピラン類およびピラノピリジン類、それらの製法並びに用途

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6033433B2 (ja) * 1978-11-08 1985-08-02 フアイザ−・インコ−ポレ−テツド ハロゲン置換ベンゾピラン−４−カルボン酸およびその誘導体
JPS63303977A (ja) * 1987-05-16 1988-12-12 サンド・アクチエンゲゼルシャフト 新規ベンゾ［ｂ］ピラン類およびピラノピリジン類、それらの製法並びに用途

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5646310A (en) * 1993-04-23 1997-07-08 Chugai Seiyaku Kabushiki Kaisha N-(2-cyanoethyl)-6-fluoroalkyl-2h-1-benzopyran derivatives
US5470861A (en) * 1994-08-04 1995-11-28 Hoffmann-La Roche Inc. Method of promoting hair growth
WO2001072727A1 (fr) * 2000-03-27 2001-10-04 Shiseido Co., Ltd. Toniques capillaires
JPWO2005027904A1 (ja) * 2003-09-22 2006-11-24 日本新薬株式会社 育毛剤

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