Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2002-11-22
2003-11-25
Raymond, Richard L. (Department: 1624)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S275000, C514SDIG001, C544S320000, C544S323000, C424S070210, C424S443000, C424S450000
Reexamination Certificate
active
06653317
ABSTRACT:
CROSS-REFERENCE TO PRIORITY APPLICATION
This application claims priority under 35 U.S.C. §119 OF FR-98/09509, filed Jul. 24, 1998, assigned to the assignee hereof and hereby expressly incorporated by reference.
BACKGROUND OF THE INVENTION
1. Technical Field of the Invention
The present invention relates to novel 2-amino-4-alkylaminopyrimidine 3-oxide chemical compounds, to compositions comprised thereof and to the use of such novel compounds/compositions as active principles for inducing and/or stimulating hair growth and/or for preventing hair loss.
2. Description of the Prior Art
In human subjects the growth and renewal of the hair are principally determined by the activity of the hair follicles. This activity is cyclic and essentially entails three phases, i.e., the anagenic phase, the catagenic phase and the telogenic phase.
The active anergenic phase, or growth phase, which lasts for several years and during which the hair elongates, is followed by a very short and transient catagenic phase which lasts for a few weeks, and then a rest or quiescent phase, designated the telogenic phase, which lasts for a few months.
At the end of the rest period, the hair falls out and another cycle begins anew. The head of hair is thus under constant renewal, and out of the approximately 150,000 hairs on a head of hair, at any given instant approximately 10% are at rest and will thus be replaced within a few months.
However, different causes can lead to a considerable, temporary or permanent, loss of hair. Alopecia is essentially due to a disruption in hair renewal which occasions, in a first stage, an acceleration of the frequency of the cycles, at the expense of the quality of the hair and then at the expense of its quantity. A gradual depletion of the head of hair takes place by regression of the so-called “terminal” hairs at the downy stage. Certain regions are preferentially affected, in particular the temples or frontal bulbs in men, and in women, diffuse alopecia of the vertex is observed.
By the term “alopecia” are intended the entire family of afflictions of the hair follicle, the final consequence of which is the partial or general permanent loss of the hair. In a large number of cases, early loss of the hair arises in genetically predisposed individuals and especially affects men. This more particularly applies to androgenetic or androgenic or even androgeno-genetic alopecia.
Active substrates for suppressing or reducing alopecia, and in particular for inducing or stimulating hair growth or reducing hair loss, have long been considered desiderata in the cosmetics and pharmaceutical industries.
In this respect, a large number of very diverse active compounds have already been suggested for such purposes, for example, 2,4-diamino-6-piperidino-pyrimidine 3-oxide or “Minoxidil” described in U.S. Pat. Nos. 4,139,619 and 4,596,812, or the many derivatives thereof, such as those described, for example, in EP-0,353,123, EP-0,356,271, EP-0,408,442, EP-0,522,964, EP-0,420,707, EP-0,459,890 and EP-0,519,819.
Nonetheless, serious need continues to exist for yet other active agents/species potentially more active and/or less toxic than those active substrates to date characterizing the state of this art.
SUMMARY OF THE INVENTION
Accordingly, a major object of the present invention is the provision of novel 2-amino-4-alkylaminopyrimidine 3-oxide compounds having the structural formula (I):
in which R
1
is an alkyl radical having from 5 to 20 carbon atoms, and Z is either a hydrogen atom or a radical −OR
2
, wherein R
2
is an alkyl radical having from 1 to 12 carbon atoms, as well as the acyl derivatives or acid addition salts thereof.
The subject compounds are well suited as active principles for inducing and/or stimulating hair growth and/or preventing hair loss.
DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OF THE INVENTION
More particularly according to the present invention, it is known to this art that certain polyunsaturated fatty acids, in particular those having 20 carbon atoms, such as arachidonic acid, dihomo-&ggr;-linolenic acid and eicosapentaenoic acid, can be converted in vivo, under the influence of certain specific enzymes contained in living cells, in particular epithelial cells, into certain yet other compounds of eicosanoid type which are useful to the body.
Thus, it is known to this art that the enzymes designated cyclooxygenated generate, from the different fatty acids indicated above, particularly from arachidonic acid, eicosanoids of prostaglandin and thromboxane type, and that the enzymes deemed lipoxygenases are responsible for the formation of eicosanoids of leukotriene type and other hydroxylated acyclic acids containing 20 carbon atoms. Depending on the nature of the enzyme with which it reacts first, the same given polyunsaturated fatty acid (or substrate) may be responsible for the formation of several different metabolites, namely, for example, prostaglandins and leukotrienes.
Cyclooxygenase activity can be defined as the enzymatic activity which converts certain polyunsaturated fatty acids into cyclized oxygenated compounds which are, indeed, highly unstable endoperoxides which thereafter enter the subsequent metabolic pathways.
Prostaglandin-endoperoxide synthase, or cyclooxygenase (or PGHS, EC 1.14.99.1), which is a haemoprotein, is an example of these enzymes exhibiting such activity. It is involved in one of the metabolic pathways of prostaglandins.
It too is known that the enzymatic transformations indicated above and the various reaction products resulting therefrom exert an appreciable influence on the mechanisms of growth of body and/or head hair.
In this respect, it has now been shown that by promoting one or other of the two enzymatic pathways, cyclooxygenated or lipoxygenated, in skin and/or scalp cells, it is possible to substantially modify the growth of body and/or head hair. Compare EP-94/402,055, assigned to the assignee hereof.
Essentially, in the aforesaid patent application, promoting one of the pathways over the other is described, by the administration of a combination of compounds combining an inhibitor of one of the pathways with a stimulator of the other pathway.
Even more specifically, it has now been shown that the growth of body and/or head hair can be promoted and/or their loss can be controlled by promoting the cyclooxygenase pathway, for example by activating PGHS and inhibiting the lipoxygenase pathway.
The involvement of these enzymes in several metabolic pathways and the consequences which may ensue from deregulating their functioning are such that extensive research has been undertaken in order to develop active agents with the capacity either of increasing or of reducing the activity of these enzymes.
Arachidonic acid metabolites, nitrogen monoxide and nitrogen-monoxide-donating compounds, stanozolol, glutathione-donating compounds, calcium ionophores, anthocyanosides, bioflavonoids, platelet activating factors (PAF), pro-inflammatory cytokines agents and bacterial endotoxins are recognized, in particular, in the field of cyclooxygenase activators.
Similarly, illustrative is 6-chloro-2,3-dihydroxy-1,4-naphthoquinone (CNDQ), which has the particular feature of being both a lipoxygenase inhibitor and a cyclooxygenase stimulator (C. J. Bedord et al.,
The Journal of Investigative Dermatology
, 81:566-571 (1983)).
However, most of these species present the major drawback of having a broad functional spectrum, which entails that, in general, they have no genuine specificity for cyclooxygenase. In this regard, the literature on this subject reflects a wide variety of interpretation. These substrates can also be labile or their activity can depend on their concentration, which makes them difficult to administer.
The present inventors have thus sought to develop novel compounds which have activity at least on PGHS, and which would then be considered cyclooxygenase activators.
After considerable research, it has now surprisingly and unexpectedly been determined that the 2-amino-4-alkylaminopyrimidine 3
Galey Jean-Baptiste
Mahe Yann
Michelet Jean-François
Pichaud Patrick
Balasubramanian Venkataraman
Burns Doane Swecker & Mathis L.L.P.
Raymond Richard L.
Societe l'Oreal S.A.
LandOfFree
Pyrimidine 3-oxide compounds for inducing/stimulating hair... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pyrimidine 3-oxide compounds for inducing/stimulating hair..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyrimidine 3-oxide compounds for inducing/stimulating hair... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3173525