WO1989006234A1 - Amines a substitution n,n et utilisation de telles amines en vue de promouvoir la croissance des cheveux - Google Patents

Amines a substitution n,n et utilisation de telles amines en vue de promouvoir la croissance des cheveux Download PDF

Info

Publication number
WO1989006234A1
WO1989006234A1 PCT/US1988/004690 US8804690W WO8906234A1 WO 1989006234 A1 WO1989006234 A1 WO 1989006234A1 US 8804690 W US8804690 W US 8804690W WO 8906234 A1 WO8906234 A1 WO 8906234A1
Authority
WO
WIPO (PCT)
Prior art keywords
amine
compound according
hydrogen
functional
compounds
Prior art date
Application number
PCT/US1988/004690
Other languages
English (en)
Inventor
Gail S. Bazzano
Original Assignee
Bazzano Gail S
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bazzano Gail S filed Critical Bazzano Gail S
Publication of WO1989006234A1 publication Critical patent/WO1989006234A1/fr

Links

Classifications

    • 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
    • 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
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/50—Three nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
    • C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
    • C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
    • C07D251/40—Nitrogen atoms
    • C07D251/54—Three nitrogen atoms
    • C07D251/70—Other substituted melamines

Definitions

  • This invention relates to novel compositions of matter and methods of their preparation, as well as to known compounds which have now been surprisingly discovered to be useful as hair growth enhancers. These compounds are useful in mammals (e.g. humans and domestic animals) for promotion of hair growth.
  • the hair follicle In contrast to most epithelial structures, the hair follicle does not grow continuously throughout its life, but passes through a cycle called the pilar cycle.
  • the pilar cycle comprises essentially three phases - - namely, the anagen or growth phase during which hair is produced, normally lasting about three to seven years; the catagen phase when growth stops and the follicle atrophies, lasting about three to four weeks; and the telogen phase, which is a rest period for the follicle during which the hair progressively separates and finally falls out, and normally lasting about three to four months.
  • the telogen phase Normally 80 to 95 percent of the follicles are in the anagen phase, less than 1 percent being in the catagen phase, and the rest being in the telogen phase.
  • the telogen phase hair is uniform in diameter with a slightly bulbous, non-pigmented root
  • the anagen phase hair has a large colored bulb at its root.
  • Alopecia results when the pilar cycle is disturbed, resulting in excessive hair loss.
  • the most frequent phenomenon is a shortening of the hair growth phase due to cessation of cell proliferation. This results in an early onset of the catagen phase, and consequently a large number of hairs in the telogen phase during which the follicles are detached from the dermal papillae, and the hairs fall out.
  • This shortening of the growth or anagen phase of the pilar cycle may have different origins, among which are very diverse pathological origins such as febrile conditions, mental stresses, hormonal problems (such as androgenetic alopecia due to male hormones) and secondary effects of drugs.
  • Alopecia may also be due to age and to a slowing down of mitotic activity.
  • This dysfunction of the biological mechanism of hair growth leading to alopecia may be regarded as a disease. While there are other causes of alopecia such as greasy or oily scalp due to seborrhea and the dandruff accompanying it, the present invention is not directed to treating these extraneous causes of alopecia, but rather to treating the organic dysfunction of the hair follicle.
  • Minoxidil a potent antihypertensive
  • a hair growth promotiong agent see U.S. Patents 3,461,461; 3,973,016; and 3,464,987.
  • the topical compound When the topical compound is absorbed, the systemic side effects include fluid retention, tachycardia, dyspnoea, gynaecomastia, fatigue, nausea and cardiotoxicity.
  • This invention provides novel compounds as well as known compounds which have been discovered to have important hair growth promotiong properties, particularly increasing and stimulating hair growth on mammalian skins, prolonging the anagen phase of the hair cycle, and converting vellus hair to growth as terminal hair, but which have much less toxicity and antihypertensive properties as compared to minoxidil. According to the present invention, novel compounds have been found of the formula:
  • R is a multifunctional amine moiety having at least n amine-functional nitrogen sites, n equals 2 to about 8, and B are disubstituted heterocyclic N-oxide moieties which are attached to amine-functional nitrogen atoms of R, and each B is independently selected from the group consisting of pyridines, pyrimidines and triazines, but when R is
  • At least one B is not 2,4-diaminopyrimidine-3-oxide.
  • the hair growth promotion compositions of the invention may also contain a retinoid.
  • the present invention provides an important advance in the search for compounds which will be more effective for promotiong hair growth, and can be used topically at higher concentrations than is possible with minoxidil.
  • the promotion of hair growth or increasing the rate of hair growth it will be understood that one of more of the following is meant: increasing the rate of hair growth on the scalp; stimulating hair follicles of the skin; prolonging the anagen phase of the hair cycle; converting vellus hair to growth as terminal hair; and/or treating alopecias caused by organic dysfunction of the hair follicle.
  • the novel and known compounds of the present invention are formed by the union of two or more N-oxide moieties or subunits represented by the letter B united by a single amine moiety represented by the letter R to form a compound which has more than one N-oxide site per molecule.
  • the N-oxide site is a primary active site in compounds capable of promoting hair growth.
  • N-oxide subunits are known per se in the art and are described particularly as parts of molecules useful in the treatment of hypertension.
  • Such compounds include the N-oxide pyrimidines, which are described for example in U.S. Patents 3,461,461; 3,973,016; and 3,464,987, and British Patent 1,486,682.
  • N-oxide pyridines are disclosed for example in U.S. Patent 4,021,562.
  • the two known compounds of Formula I namely wherein R is a piperazinyl or bis-piperidinyl group, n is 2 and both B are 2,4-diaminopyrimidine-3-oxide, are described in A.
  • the amine moieties which may be used as R in Formula I are those derived from a number of different amines having two or more amine-functional sites, preferably on two or more amine-functional nitrogen atoms.
  • the amine-functional nitrogen atoms may be primary or secondary amines so that when reacted with the heterocyclic N-oxide compounds to add the B moieties, secondary or tertiary amines are formed.
  • the compounds of the present invention are formed using the two or more nucleophilic hetero atom sites on acyclic, aliphatic amines; on aliphatic, carbocyclic amines; on polycyclic and aromatic amines; and on other mono- and disubstituted amines having two or more sites for reaction.
  • R amine moieties include the classes of aliphatic amines, cycloaliphatic amines, aromatic amines, heterocyclic amines and polyamines, each having two or more unsubstituted nitrogen sites, and preferably two or more nitrogen atoms with unsubstituted sites.
  • the amines may also be substituted or unsubstituted at other nitrogen, carbon or hetero atom sites.
  • suitable R amine moieties include the following (carbon hydrogens have been omitted in many examples for clarity):
  • R moieties the unattached bonds from the nitrogen atoms may be attached to either B groups (i.e., N-oxide moieties) or A groups which may be, for example, hydrogen or substituted or unsubstituted alkyl, cycloalkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloaryl, alkenyl or aryl groups, wherein the substituents on these groups may be alkyl, halo or alkoxy.
  • B groups i.e., N-oxide moieties
  • a groups which may be, for example, hydrogen or substituted or unsubstituted alkyl, cycloalkyl, alkoxy, halo, haloalkyl, haloalkoxy, haloaryl, alkenyl or aryl groups, wherein the substituents on these groups may be alkyl, halo or alkoxy.
  • the A groups are either hydrogen or lower alkyl, but other substituents include, for example, lower alkenyl, lower alkoxyalkyl, lower cycloalkyl, lower aryl, lower alkaryl, lower aralkyl, lower alkaralkyl, lower alkoxyaralkyl, lower haloaralkyl, lower alkylphenylthio, and halophenylthio.
  • lower means C 1-8 for aliphatic substituents and C 6-16 for aromatic substituents.
  • R moieties at least two, and preferably two to about five of the unattached nitrogen bonds are connected to B moieties, and the remainder are attached to A groups as defined above.
  • B moieties Preferably, only one B moiety is attached to each nitrogen atom, but it will be understood that two B moieties could be attached to an amine-functional nitrogen atom where that is sterically possible.
  • the B moieties on a given R moiety of Formula I may be independently selected, and need not be the same on a given R moiety, so that different B moieties may be present in a given compound.
  • the B moieties useful in the compounds of Formula I are generally described as di-substituted heterocyclic N-oxide moieties, which are similar to those present in minoxidil and its analogs.
  • N-oxide moieties may be represented by the following formula:
  • W and Y are nitrogen or carbon atoms and may.be the same or different; each A' may be independently selected from the same group as the A group described above, particularly hydrogen or substituted or unsubstituted alkyl, cycloalkyl, alkenyl or aryl, and may be additionally selected from carboxyacyl; R' may be A' or NA' wherein A' is as described above.
  • the unattached bond at the ring position para to the N-oxide group is the position for attachment of the B moiety to the R moiety of Formula I.
  • the heterocylic B moieties have a single nitrogen atom in the ring and may be referred to as pyridines; where one of Y and W is carbon and the other is nitrogen, the heterocyclic rings have two nitrogen atoms and may be referred to as pyrimidines; and where Y and W are both nitrogen, the heterocyclic rings have three nitrogen atoms and may be referred to as triazines.
  • both A' groups are preferably hydrogen and R' is preferably NH 2 .
  • Other preferred substituents on the heterocyclic N-oxide B moieties are amines substituted with carboxyacyl groups. Examples of such pyrimidine B moieties are described in my published PCT patent applications US85/00556 (WO85/04577) and US85/01329 (WO86/00616), the disclosures of which are incorporated herein by reference. In such B moieties, R' equals NA' , and one of the A' groups on each amine substituent is hydrogen, while the other is a carboxyacyl group.
  • the carboxyacyl groups may be, for example:
  • novel compounds of the invention as well as the known compounds useful in the methods of the invention, can be formed by generally straightforward processes either known in the art or which will be evident to those of ordinary skill in the art.
  • halogenated compounds of Formula II wherein the substituent para to the N-oxide group is a chlorine or bromine atom, for example, may be reacted with hydrides of the R moieties, i.e., compounds in which the R moieties have hydrogen atoms on the nitrogen bonds to which the B moieties are to be attached.
  • the compounds are reacted in the presence of an unreactive solvent, such as o-xylene, with at least a slight excess of the R moiety compound which is required for a stoichiometric reaction with the B moiety compound.
  • an unreactive solvent such as o-xylene
  • carboxyacylates e.g., carbamates or oxamates of these compounds
  • the reaction product described above can be reacted with a suitable carboxyacylatmg agent.
  • carboxyacylatmg agent can be used to produce these carboxyacylates, especially suitable are the anhydrides, mixed anhydrides and acid chlorides of alkanoic, cycloalkanoic, alkenoic, cycloalkenoic, aralkanoic, aromatic and heterocyclic carboxylic acids.
  • These anhydrides and acid chlorides can also have substituents on any carbon except the carbonyl carbon with any of a wide variety of atomic or molecular moieties unreactive with the amine groups on the B moieties.
  • substituents are alkyl, e.g., methyl, butyl, decyl; alkoxy, e.g., methoxy, ethoxy, pentyloxy; aklythio, e.g., methylthio, propylthio, heptylthio; dialkylamino, e. g.
  • dimethylamino diethylamino , dihexylamino
  • alkoxycarbonyl e.g., methoxycarbonyl, propoxycarbonyl, nonoxycarbonyl
  • carboxyacyl e.g., acetyl, butyryl
  • carboxamido e.g., benzamido, aetamido
  • nitro fluoro; cyano and the like.
  • Chlorine, bromine and iodine can also be substituents on aromatic portions of carboxyacylating agents.
  • Suitable anhydrides which can be reacted as the carboxyacylatmg reagents are acetic anhydride, propionic anhydride, butyric anhydride, isobutyric anhydride, acrylic anhydride, crotonic anhydride, cyclohexane-carboxylic anhydride, benzoic anhydride, napthoic anhydride, furoic anhydride and the like, as well as the corresponding anhydrides substituted with one or more of the above-mentioned substituents.
  • Suitable acid chlorides are acetyl chloride, propionyl chloride, butyryl chloride, isobutyryl chloride, decanoyl chloride, acryloyl chloride, crotonoyl chloride, cyclohexanecarbonyl chloride, 3-cyclohexenecarbonyl chloride, phenylacetyl chloride, succinyl chloride, benzoyl chloride, naphthoyl chloride, furoyl chloride, ethyl oxalyl chloride, ethyl chloroformate, 3-pyridinecarbonyl chloride, phthaloyl chloride and the like, as well as the corresponding acid chlorides substituted with one or more of the above-mentioned substituents.
  • At least one molecular equivalent of carboxyacylatmg agent should be used for the introduction of each carboxyacyl moiety.
  • reactive carboxyacylating agents such as acetic anhydride
  • a diacyl compound is usually obtained even with only one molecular equivalent of carboxyacylating agent. In such cases, some of the amine groups on the B moieties do not form carboxyacylates.
  • the carboxyacylation usually takes place rapidly in the range of -20 to about +50°C.
  • Suitable diluents are ethers; e.g., diethyl ether or tetrahydrofuran; ketones, e.g., acetone or methylethyl ketone; esters, e.g., methyl acetate or ethyl acetate; acetonitrile; pyridine and the like.
  • the desired carboxyacylate often separates from the reaction mixture in crystalline form and can be separated in the usual manner; for example, by filtration or centrifugation. Alternatively, the diluent can be evaporated, preferably at reduced pressure.
  • the carboxyacylates can be purified by conventional techniques; for example, by recrystallization from a suitable solvent or mixture of solvents.
  • novel compounds of the invention as described above, as well as the two similar compounds described by Catto, et al., are relatively weak and non-toxic when administered orally as antihypertensive agents. It has been unexpectedly discovered that the subject compounds, when applied topically to mammalian skin, in an effective amount, can stimulate or improve the rate of hair growth and prolong the anagen phase of the hair cycle. Moreover, these compounds can be used in high concentrations in topical solutions and can be effective in treatment of alopecia. Typically, these compounds are useful as the active ingredients of different types of preparations such as lotions, solutions, ointments, creams, sprays and the like.
  • the compounds of the present invention which form the active ingredients in the hair treatment preparations can be used in combinations with retinoids as described in my published PCT patent applications US81/00338 (WO82/02833) and US82/01593 (WO83/02558), in that these combinations can exhibit synergism.
  • the combinations can improve or stimulate the rate of hair growth to a greater extent than the individual active ingredients of the combinations alone.
  • Suitable retinoid active ingredients for use in this invention include, for example, derivatives of retinoic acid which have been described in PCT applications US81/00338 and US82/01593, the disclosures of which are incorporated herein by reference.
  • Preparations such as lotions, creams, conditioners, and the like, including the aforementioned compounds as the active ingredients, can be applied topically to the skin for stimulating or improving the rate of hair growth.
  • the compounds of the present invention are not very toxic, in comparison with minoxidil, and when applied topically to the skin in high concentration have excellent penetration and a long lasting effect, in producing hair growth in an animal model for androgenetic alopecia.
  • retinoids in combination with the subject compounds of this application can exhibit synergism in the animal model studied.
  • topical as employed herein, relates to the use of the above compounds, incorporated in a suitable pharmaceutical carrier, and applied at the site of baldness for exertion of local action. Accordingly, such topical compositions include those pharmaceutical forms in which the compound is applied externally by contact with the skin surface to be treated.
  • Conventional pharmaceutical forms for this purpose include ointments, lotions, pastes, jellies, sprays, aerosols, and the like.
  • ointment embraces formulations (including creams) having oleaginous, absorptive, water-soluble and emulsion-type bases; e.g., petrolatum, lanolin, polyethyene glycols, as well as mixtures of these.
  • the percentage by weight of the compounds of the invention utilized preferably ranges from about 1% to about 20% of the pharmaceutical preparations; the aforesaid pharmaceutical carriers for topical application constitute a major amount of the preparation.
  • the active compounds may also be used in a free flowing bead formulation by entrapment with a syneresis-free polymeric network which is hydrophobic. Loading as great as 60-80% should be achieved within the polymeric lattice. In this matrix the functional hair growth agent is held by microsorption and protected from hydrolysis and other modes of decomposition, providing prolonged shelf-life and in a form superior to an emulsion.
  • compositions contemplated by this invention include pharmaceutical compositions suited for topical and systemic action.
  • the following Examples illustrate the administration vehicles for the present invention.
  • the methods of administration may vary by lotion, cream, ointment, polymeric beadlets, supplement to chow, coating for seeds, etc. These Examples are only meant to be illustrative and do not limit the mode of administration nor the ingredients which can be admixed to the present invention, nor the amount which may be used.
  • the active ingredients in this example are entrapped within an acrylate copolymer.
  • the hydrophobic polymer is plasticized by most entrapped ingredients. The degree of plasticization determines whether the beads are soft, spreadable, and film-forming with minimal pressure or hard with the ability to withstand shearing of light intensity.
  • a rodent model of hypotrichosis has been developed which is useful as an animal model of androgenetic alopecia.
  • the model displays some of the characteristics of male pattern alopecia in humans.
  • Extreme hair loss is developed after puberty in males. It is typified by initial hair loss on the crown of the head, continuing to the development of hypotrichosis in these animals, as shown by fewer and smaller hair follicles and greatly enlarged sebaceous glands, especially over the crown of the head and the shoulders and upper back. The limbs tend to remain hairy. The females eventually develop male pattern alopecia but not to the same degree as the males.
  • the active compounds caused an increase of more than 25% in the amount of hair growth found over the amount of growth found in animals treated with the placebo lotion.
  • the unexpected novel advantages to be gained from the use of the instant invention are: improved solubility and improved stability and activity of active compounds and the increased percutaneous absorption leading to longer action of compounds; the excellent penetration of skin is due in part to the hydrophilic and lipophilic substituents; and compatability of compounds with non-polar solvents useful for the preservation of the polar groups while in contact with the skin. Furthermore, the less-toxic nature of these compounds allows a greater concentration of the active compound to be applied topically without unwanted side effects.

Landscapes

  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Les nouveaux composés décrits sont représentés par la formule générale RBn, où R représente une fraction d'amine multifonctionnelle ayant au moins n sites d'azote fonctionnels pour l'amine, n étant égal à un chiffre compris entre 2 et environ 8, et B représente des fractions de N-oxyde hétéroxycliques bisubstituées qui sont fixées aux atomes d'azote fonctionnels pour l'amine de R, chaque B étant séparément sélectionné dans le groupe composé de pyridines, de pyrimidines et de triazines. Ces nouveaux composés et des composés similaires connus sont utiles en vue de promouvoir la croissance des cheveux par application topique sur la peau de mammifères. Des composés particulièrement préférés de la présente invention sont ceux dans lesquels les fractions de B sont bisubstituées avec des groupes d'amine adjacents à la position N-oxyde du noyau hétérocyclique.
PCT/US1988/004690 1987-12-28 1988-12-28 Amines a substitution n,n et utilisation de telles amines en vue de promouvoir la croissance des cheveux WO1989006234A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US13804887A 1987-12-28 1987-12-28
US138,048 1987-12-28
US15656888A 1988-02-17 1988-02-17
US156,568 1988-02-17

Publications (1)

Publication Number Publication Date
WO1989006234A1 true WO1989006234A1 (fr) 1989-07-13

Family

ID=26835821

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1988/004690 WO1989006234A1 (fr) 1987-12-28 1988-12-28 Amines a substitution n,n et utilisation de telles amines en vue de promouvoir la croissance des cheveux

Country Status (1)

Country Link
WO (1) WO1989006234A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2663327A1 (fr) * 1990-06-19 1991-12-20 Oreal Nouveaux derives de diamino-2,4 triazine-1,3,5 et leur utilisation pour le traitement et la prevention de la chute des cheveux.
WO1999062486A1 (fr) * 1998-06-03 1999-12-09 Gpi Nil Holdings Inc. Compositions pour la croissance des cheveux a base de n-oxydes de ketones, de thioesters, d'amides ou d'esters heterocycliques, et utilisation de ces compositions
US6004993A (en) * 1997-06-04 1999-12-21 Gpi Nil Holdings, Inc. N-linked sulfonamide of heterocyclic thioester hair growth compounds and uses
US6172087B1 (en) 1998-06-03 2001-01-09 Gpi Nil Holding, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
US6187784B1 (en) 1998-06-03 2001-02-13 Gpi Nil Holdings, Inc. Pipecolic acid derivative hair growth compositions and uses
US6187796B1 (en) 1998-06-03 2001-02-13 Gpi Nil Holdings, Inc. Sulfone hair growth compositions and uses
US6271244B1 (en) 1998-06-03 2001-08-07 Gpi Nil Holdings, Inc. N-linked urea or carbamate of heterocyclic thioester hair growth compositions and uses
US6274617B1 (en) 1998-06-03 2001-08-14 Gpi Nil Holdings, Inc. Heterocyclic ester and amide hair growth compositions and uses
US6274602B1 (en) 1998-06-03 2001-08-14 Gpi Nil Holdings, Inc. Heterocyclic thioester and ketone hair growth compositions and uses
US6331537B1 (en) 1998-06-03 2001-12-18 Gpi Nil Holdings, Inc. Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds
US6429215B1 (en) 1998-06-03 2002-08-06 Gpi Nil Holdings, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BOLL. CHIM. FARM., 121, 16-26, published 1982, "2,4-Diamino-6-Piperidinil E 6-Piperazinilpirimidine 3-Ossido, Nuovi Analoghi Del Minossidile". See Tabella I, page 17, Tabella II, page 19, and Compounds 3 and 5, page 18. *

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991019701A1 (fr) * 1990-06-19 1991-12-26 L'oreal Nouveaux derives de diamino-2,4 triazine-1,3,5 et leur utilisation pour le traitement et la prevention de la chute des cheveux
FR2663327A1 (fr) * 1990-06-19 1991-12-20 Oreal Nouveaux derives de diamino-2,4 triazine-1,3,5 et leur utilisation pour le traitement et la prevention de la chute des cheveux.
US6191125B1 (en) 1997-06-04 2001-02-20 Gpi Nil Holdings, Inc. Small molecule pipecolic acid derivative hair growth compositions and uses
US6194440B1 (en) 1997-06-04 2001-02-27 Gpi Nil Holdings, Inc. Small molecule carbamate or urea hair growth compositions and uses
US6004993A (en) * 1997-06-04 1999-12-21 Gpi Nil Holdings, Inc. N-linked sulfonamide of heterocyclic thioester hair growth compounds and uses
US6177455B1 (en) 1997-06-04 2001-01-23 Gpi Nil Holdings, Inc. Pyrrolidine derivative hair growth compositions and uses
US6172087B1 (en) 1998-06-03 2001-01-09 Gpi Nil Holding, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
US6187796B1 (en) 1998-06-03 2001-02-13 Gpi Nil Holdings, Inc. Sulfone hair growth compositions and uses
US6187784B1 (en) 1998-06-03 2001-02-13 Gpi Nil Holdings, Inc. Pipecolic acid derivative hair growth compositions and uses
WO1999062486A1 (fr) * 1998-06-03 1999-12-09 Gpi Nil Holdings Inc. Compositions pour la croissance des cheveux a base de n-oxydes de ketones, de thioesters, d'amides ou d'esters heterocycliques, et utilisation de ces compositions
US6271244B1 (en) 1998-06-03 2001-08-07 Gpi Nil Holdings, Inc. N-linked urea or carbamate of heterocyclic thioester hair growth compositions and uses
US6274617B1 (en) 1998-06-03 2001-08-14 Gpi Nil Holdings, Inc. Heterocyclic ester and amide hair growth compositions and uses
US6274602B1 (en) 1998-06-03 2001-08-14 Gpi Nil Holdings, Inc. Heterocyclic thioester and ketone hair growth compositions and uses
US6331537B1 (en) 1998-06-03 2001-12-18 Gpi Nil Holdings, Inc. Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds
US6429215B1 (en) 1998-06-03 2002-08-06 Gpi Nil Holdings, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
AU761737B2 (en) * 1998-06-03 2003-06-12 Gpi Nil Holdings, Inc. N-oxide of heterocyclic ester, amide, thioester, or ketone hair growth compositions and uses
US7153883B2 (en) 1998-06-03 2006-12-26 Gpi Nil Holdings Inc. Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds

Similar Documents

Publication Publication Date Title
EP0540629B1 (fr) Utilisation de derives de pyrimidine 3-oxyde pour freiner la chute des cheveux et compositions topiques mises en oeuvre
EP0519819B1 (fr) Composition pour freiner la chute des cheveux et pour induire et stimuler leur croissance à base de dérivés de pyrimidines N-oxyde trisubstitués en position 2,4 et 6 par une fonction amine, et nouveaux composés pyrimidines N-oxyde
EP0420707B1 (fr) Compositions destinées à être utilisées pour freiner la chute des cheveux et pour induire et stimuler leur croissance, contenant des dérivés de l'amino-2 pyrimidine oxyde-3 et nouveaux composés dérivés de l'amino-2 pyrimidine oxyde-3
US4973474A (en) 2,4-diaminopyrimidine 3-oxide derivatives and their use for the treatment and prevention of hair loss
JP3073047B2 (ja) 毛髪の脱落防止並びに発育促進用組成物
EP0522964B1 (fr) Compositions pour freiner la chute des cheveux et pour induire et stimuler leur croissance à base de dérivés de 2,4-diamino pyrimidine 3-oxyde
EP0187854A1 (fr) Oxydes de pyrimidine substitues utiles pour favoriser la croissance des cheveux
EP0408442B1 (fr) Dérivés de pyrimidine oxyde-3 halogénés, leur utilisation pour le traitement et la prévention de la chute des cheveux et pour stimuler leur repousse
WO1989006234A1 (fr) Amines a substitution n,n et utilisation de telles amines en vue de promouvoir la croissance des cheveux
US6156899A (en) N-aryl-2-hydroxyalkylamido compositions for inducing/stimulating hair growth and/or retarding hair loss and/or for treating hyperseborrhea and/or acne
US5137888A (en) N,N- substituted amines and use thereof in hair growth promotion
US6291532B1 (en) Use of N-aryl-2-hydroxyalkylamides for stimulating or inducing hair growth and/or arresting hair loss
EP0728461B1 (fr) Composition pour augmenter la croissance de cheveux
WO1989007595A1 (fr) Derives de spiroaza de n-oxydes heterocycliques et leur emploi dans la stimulation de la croissance des cheveux
FR2677247A1 (fr) Composition pour freiner la chute des cheveux et pour induire et stimuler leur croissance, a base de derives de pyridine-1 oxyde.
EP0427625B1 (fr) Nouveaux sels internes des hydroxydes de diamino-2,4 alcoxy-6 sulfooxy-3 pyrimidinium et leur utilisation pour le traitement et la prévention de la chute des cheveux
KR0171446B1 (ko) 발모제 조성물
WO1991019701A1 (fr) Nouveaux derives de diamino-2,4 triazine-1,3,5 et leur utilisation pour le traitement et la prevention de la chute des cheveux

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE