MXPA99006658A - Use of agonists of adrenergic beta-3 receptors for preparing wound-healing medicines - Google Patents

Abstract

The invention concerns the use of agonists of adrenergic beta-3 receptors for preparing wound-healing medicines and pharmaceutical compositions for said use.

Description

USE OF AGONISTS OF BETA-3 ADRENERGIC RECEPTORS FOR THE PREPARATION OF MEDICINES CICATRIZANTS FIELD OF THE INVENTION The present invention relates to a new indication of agonists of beta-3 adrenergic receptors. More particularly, the invention relates to the use of beta-3 adrenergic receptor agonists for the preparation of healing medicaments. It is known that beta-3 adrenergic receptor agonists can be used for the treatment of obesity and diabetes, although the clinical evidence of this activity has not been provided with certainty. It is also known that beta-3 adrenergic receptor agonists, hereinafter briefly termed "β3-agonists", were proposed as intestinal spasmolytics, for the treatment of gastrointestinal diseases, more particularly inflammatory bowel diseases, (IBD English "inflammatory bowel disease") Ref .: 30812 of the irritable bowel syndrome and for the protection of the gastrointestinal tract against the side effects of non-steroidal anti-inflammatory drugs. The term "β3-agonists" includes compounds that are beta receptor agonists that have been defined as "atypical" or "no ßi no ß2" and which are currently recognized as a subtype of the adrenergic receptor called "β3". The treatment of wounds that do not heal is a serious clinical problem, difficult to solve since wound healing involves a complex series of overlapping phenomena that are difficult to control as a whole. Growth factors, especially the growth factor of the basic fibroblasts (bFGF, of the "basic Fibroblast Growth Factor", Biol. Pharm. Bull., 1996, 19 (4), 530-535) and the factor of the fibroblasts acid (aFGF, J. Invest. Dermatoi., 1995, 104, 850-855) as well as sphingosylphosphorylcholine, J. Invest. Dermatol, 1996, 106, 232-237, were proposed as agents for wound healing. It was now discovered that β3-agonists have a certain activity on the healing of wounds in mammals.

More particularly, it was discovered that β3-agonists act by accelerating the face of dermal wounds in diabetic mammals. Thus, according to one of its aspects, the present invention has as an object the use of β3-agonists for the preparation of pharmaceutical compositions intended to accelerate the healing of wounds. More particularly, the invention relates to the use of β3-agonists for the preparation of healing medicaments. Some ß3-agonists suitable for use according to the present invention are represented by the formula (I). wherein x represents hydrogen, a halogen, a trifluoromethyl group or a (C? -C) alkyl group; R represents hydrogen, a methyl group, unsubstituted or substituted by a carboxy or lower carbalkoxy group and their pharmaceutically acceptable salts, indicated in EP 0 211 721 and EP 0 303 546 which describe the compounds of formula (I) useful as intestinal spasmolytics. Among the compounds of formula (I), the compounds: • 2- [(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; • 2- [(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl) amino] -1- (3-chlorophenyl) ethanol; • 2- [(7-carbethoxymethoxy-1,2,4,4-tetrahydronaphth-2-yl) amino] -1- (3-chlorophenyl) ethanol; • 2- [(7-carbetsxymethoxy-1, 2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; • (IR, 2'RS) -2- [(7-hydroxy-l, 2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; • (SS, 2 'RS) -2- [(7-hydroxy-1,2,3,4-tetrahydroflaphth-2-yl) amino] -1-phenylethanol; • (+) - (IR) -2- [(7-hydroxy-l, 2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; • (+) - (lS) -2- [(7-hydroxy-l, 2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; • (-) - (IR) -2- t (7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl) amino] -1-phenylethanol; • (-) - (ls) -2- [(7-hydroxy-l, 2,3,4-tetrahydronaphth-2-yl) aminol-1-phenylethanol; • N- [(2R) -7-ethoxycarbonylmethoxy-1, 2,3,4-tetrahydronaphth-2-yl) - (2R) -2- (3-chlorophenyl) -2-hydroxyethanamine; • N- [(2R) -7-methoxycarbonylmethoxy-1, 2,3,4-tetrahydronaphth-2-yl) - (2R) -2- (3-chlorophenyl) -2-hydroxyethanamine; • and, in particular, N - [(2S) -7- ethoxycarbonylmethoxy-1,2,3,4-tetrahydronaphth-2-yl] - (2R) -2- (3-chlorophenyl) -2-hydroxyethanamine (SR58611 ); as well as their pharmaceutically acceptable salts, are particularly advantageous compounds. Other ß3-agonists suitable for use according to the present invention are represented by the formula (II) wherein n is 1, 2 or 3; A represents a benzofuran-2-ylo group or a phenyl group unsubstituted or substituted by one or two halogen atoms or by a (C? -C4) alkyl or trifluoromethyl group; R 'represents a hydrogen; a group (Ci-Cβ) alkyl; a functional group selected from the following groups: hydroxy; (C? -C6) alkoxy; (C-C6) alkenyloxy; (C2-Ce) alkynyloxy; (C3-C8) cycloalkyloxy; (C3-C8) cycloalkyl (C? ~ C6) alkoxy; benzyloxy; phenoxy; . mercapto; (Ci- C6) alkylthio; (C2-C6) alkenylthio; (C2-Cβ) alkynylthio; (C3-C8) cycloalkylthio; (C3-C8) cycloalkyl (C? -C6) alkylthio; benzylthio; phenylthio; ((C? -C6) alkyl) sulfinyl; ((C2-15 C6) alkenyl) sulfinyl; ((C2-C6) alkynyl) sulfinyl; (C3-C8) cycloalkylsulfinyl; ((C3-C8) cycloalkyl (C? C6) alkyl) sulfinyl; benzylsulfinyl; faith? ilsulfinil; ((C? -C6) alkyl) sulfonyl; ((C2-20 C6) alkenyl) sulfonyl; ((C2-C6) alkynyl) sulfonyl; (C3-C8) cycloalkylsulfonyl; ((C3-C8) cycloalkyl (Ci- C) alkyl) sulfonyl; benzisulfonyl; phenylsulfonyl; cyano; nitro; amino no substituted or substituted by one or two radicals, identical or different, chosen from (Ci-Cß) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C3-C8) cycloalkyl, (C3-C8) cycloalkyl (Ci-Ce) alkyl, benzyl, phenyl; carboxy; Carbalkoxy whose alkyl group is in C? -C6; ((C2-C6) alkenyloxy) carbonyl; ((C2-C6) alkynyloxy) carbonyl; (C3-C8) cycloalkyloxycarbonyl; ((C3-C8) cycloalkyl (C? -C6) alkoxy) carbonyl; 10-benzyloxycarbonyl; phenoxycarbonyl; carbamoyl unsubstituted or substituted on the amino group by one or two radicals, identical or different, chosen from the groups (O.-C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C3-C8) cycloalkyl, (C3-C8) cycloalkyl (Cx-Cβ) alkyl, benzyl and phenyl; - a group R '' 'chosen from the groups (Ci- C) alkyl substituted by a functional group; (C2-Ce) alkenyl substituted by a group functional; (C2-C6) alkynyl substituted by a functional group; phenyl (Ci-Cβ) substituted alkyl on the phenyl group by a (Ci-Cβ) alkyl or by a functional group; phenyl (C2-C6) alkenyl substituted on the phenyl group by a (d-25 Ce) alkyl or by a functional group; phenyl (C2-C6) alkynyl substituted on the phenyl group by a (Ci-Ce) alkyl or by a functional group; benzyl substituted on the phenyl group by a (Ci-Cβ) alkyl or by a functional group; phenyl, unsubstituted or substituted on the phenyl group by a (C? -C6) alkyl or by a functional group; the functional group being as defined above; - a group O-R '' ', S-R' '', SO-R '' ', S02-R' ", in , which R '' 'is as defined above for R'; - a group NR '' 'R °, where R' '' is as defined above and R ° represents hydrogen or is as defined for R '' ', or The R '' 'and R ° form, with the nitrogen to which they are bound, a group chosen from the pyrrolidino, piperidino and morpholino groups; - a COOR group '' 'or a group CO-SR' '' in which R '' 'is as defined above; - a CONR group. ' '' R ° where R '' 'is as defined above and R ° represents hydrogen or is as defined for R' '', or R '"and R ° form, with nitrogen to which are linked, a group chosen from the pyrrolidino, piperidino and morpholino groups; - a group S02NR '' 'R ° where R' "is as defined above and R ° represents hydrogen or is as defined above for R '' ', or R' '' and R ° form, with the nitrogen to which they are bound, a group selected from the pyrrolidino, piperidino and morpholino groups; R "represents - a hydrogen; - a halogen; - a group (C? -C6) alkyl; a functional group as defined above for R '; - a group OR '' ', R' '' above; - a group COOR '' ', R' '' as defined above; - a group CONR '' 'R ° where R' '' is as defined above and R ° represents hydrogen or is as defined above for R '' ', or R' "and R ° form, with the nitrogen to which they are bound, a group chosen from the pyrrolidino, piperidino and morpholino groups; w represents a direct bond or an oxygen atom; X 'represents hydrogen, a (C? -C6) alkyl or a (Ci- C6) alkylcarbonyl; Y represents hydrogen or a group A'-CH (OH) -CH2-, where A 'is identical to A, but different from benzofuran-2-yl; or X 'and Y, taken together, form a methylene group, optionally substituted by a carbalkoxy group whose alkyl group is in C? -C6; an ethylene group, optionally substituted by an oxo group; or a 1,3-propylene group; Z represents hydrogen or a (Ci-Cβ) alkyl; as well as their pharmaceutically acceptable salts, indicated in EP 0 255 415 which describes the use of the compounds of formula (II) as intestinal spasmolytics. Other ß3-agonists also useful according to the present invention are represented by the formula (III) OH) wherein E represents hydrogen, a group (Ci-Cg) alkyl, a group (C? -C) alkoxy, a phenyl group, a nitro group, a halogen atom or a trifluoromethyl group, L represents hydrogen, a group (C? -C4) alkyl, a group (C? -C4) alkoxy, a phenyl group, a nitro group, a halogen atom or E and L, together, represent a group -CH = CH-CH = CH- or CH2-CH2-CH2-CH2-, and G represents hydrogen, a chlorine atom, a hydroxy group or an OG 'group where G' represents a (Cx-C4) alkyl group unsubstituted or substituted by a hydroxy group, (C? -C4) alkoxy, (C? -C4) alkoxycarbonyl, carboxy or (C3-C7) cycloalkyl; a group (C3-C7) cycloalkyl; a (C2-C) alkanoyl group, as well as their pharmaceutically acceptable salts, indicated in EP 0 436 435 which describes the compounds of formula (III) useful as intestinal spasmolytics. Among the compounds of formula (III), N - [(6-hydroxy-1,2,3,4-tetrahydronaphthalen- (2R) -2-yl) methyl] - (2R) -2-hydroxy-2- ( 3-chlorophenyl) ethanamine (SR 59104), N - [(7-methoxy-1,2,3,4-tetrahydronaphthalene- (2R)) -2-yl) methyl] - (2R) -2-hydroxy-2 - (3-chlorophenyl) ethanamine (SR 59119), as well as its. Pharmaceutically acceptable salts are particularly advantageous compounds. Other advantageous β3-agonist compounds according to the present invention are: the compound BRL 35135 described in EP 23385, of the formula: - the compound CL 316243 described in US Pat. No. 5,061,727, of the formula: - the compound AZ 002 described in EP 218440, of the formula: the compound BMS 187257 described in US 5,321,036, of the formula: - the compound L-755507, of the formula: and the compound L-750355, of formula: described in EP611003; the compound FR-149175 described in Japan J. Pharmacol., 1997, 74, (1): 109, of the formula: - compound SB-226552, described in Int. J. Obesity, 1997, 21, Suppl.2: 560 of formula: 13 as well as the products described in the following patents / patent applications: WO 96/35671, WO 96/35670, WO 96/16038, WO 96/04233, WO 95/33724, WO 95/29159, EP 659737, WO 95/04047, EP 516349, EP 473285, EP 23385, EP 21636, EP 7205, JP 08198866, JP 08165276, JP 08157470, WO 96/16938, EP 714883, WO 96/04234, US 5,488,064, US 5,482,971, US 5,491,134, WO 95/29159, WO 95/33724, ZA 9409874, WO 95/29903, US 5,461,163, WO 95/25104, EP 659737, JP 07112958, WO 95/8527, WO 95/07284, JP 07025756, WO 95/03289, WO 95/04047, WO 95/01170, WO 94/29290, US 5,373,020, JP 06293664, WO 94/12166, EP 611003, WO 97/10825, WO 97/21666, WO 97/21665, JP 09118655, WO 97/15549, GB 2305665, EP 764640, EP 764632 , WO 97/10622. The activity of the compounds was demonstrated by means of a scar measurement test after having created a 1 cm2 skin lesion on the back of a mouse extracting a fragment of skin. Diabetic animals were subjected to the β3-agonist study versus placebo. The compound was administered orally at a rate of 10 mg / kg. The healing was evaluated by measuring daily the surface of the lesion in the treated animals and in those that had received the placebo. The results of this study showed a clear difference in healing in the animals treated with the ß3-agonist compound with respect to that of the animals that received the placebo, namely that the cure of the lesions is fulfilled in a clearly shorter term for the treated animals than for those who received the placebo. Thanks to this particular healing activity and its low toxicity that allows its use as medicines, the ß3-agonist compounds can be used in the prophylaxis and / or treatment of dermal wounds, especially in the prophylaxis and / or treatment of lower limb sores in diabetic mammals. Thus, according to another of its aspects, the present invention relates to a method for the prophylaxis and / or treatment of wounds in mammals, said method being characterized in that a prophylactic and / or effective amount of a β3-agonist compound is administered to said mammals, in need of said prophylaxis and / or said treatment. More particularly, according to a preferred aspect, the present invention has as its object a method of prophylaxis and / or treatment of wounds in mammals, said method being characterized in that it is administered to said mammals, which need said prophylaxis and / or said treatment, a prophylactic and / or effective amount of a compound selected from the compounds of formula (I), (II) and (III). The amount of active ingredient to be administered in the treatment of wounds according to the present invention depends on the nature and severity of the conditions to be treated, as well as on the potency of the compound and the weight of the patients. Generally, the dose is between 0.01 and 30 mg per kg of body weight, preferably between 0.1 and 20 mg per kg of body weight, in particular between 1 and 10 mg per kg of body weight. This dose can possibly be subdivided during the day in 2, 3 or 4 administrations. Preferably the active principle is formulated in dosage units containing 0.1 to 400 mg, and preferably 0.5 to 200 mg of active ingredient in combination with a pharmaceutical carrier. In the case of treatment by local route, which can be complementary to a systemic administration, the dosage unit depends on the severity and extension of the wounds as well as the concentration of active principle in the pharmaceutical formulation. Normally, a cream, an ointment, a gel containing 0.01 to 5%, conveniently 0.025 to 2.5%, preferably 0.1 to 1% of β3-agonist in admixture with the usual excipients for topical application is used. A lotion or, in general, a solution or a suspension in which the β3-agonist is present in concentrations of 0.0001 to 1% can also be used. In the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, rectal or local administration, the active principle can be administered in unitary forms of administration, either such as for example in lyophilized form, or either in mixture with classical pharmaceutical supports, to animals and humans for the treatment of the aforementioned conditions. Suitable unit administration forms comprise oral forms such as eventually divisible tablets, dragees, powders, granules and oral solutions or suspensions, sublingual and buccal administration forms, subcutaneous, intramuscular or intramuscular administration forms. intravenous, forms of local administration and forms of rectal administration. When preparing a solid composition in the form of tablets, the main active ingredient is mixed with a pharmaceutical carrier such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic or the like. The tablets may be coated with sucrose or other suitable materials or else treated in such a manner that they have a prolonged or delayed activity and continuously release a predetermined amount of active ingredient. A dragee preparation is obtained by mixing the active ingredient with a diluent and pouring the obtained mixture into soft or hard dragees. A preparation in the form of syrup or elixir may contain the active ingredient together with a sweetener, preferably a caloric sweetener, methylparaben and propylparaben as antiseptics, as well as a flavoring agent and an appropriate colorant. Powders or granules dispersible in water may contain the active ingredient in admixture with dispersing agents or wetting agents, or suspending agents, such as polyvinylpyrrolidone, as well as with sweeteners or flavor correctors. For a rectal administration, suppositories prepared with binders that melt at the rectal temperature are used, for example cocoa butter or polyethylene glycols. For parenteral administration, aqueous suspensions, saline solutions or sterile and injectable solutions containing pharmacologically compatible dispersing agents and / or humectants, for example propylene glycol or butylene glycol, are used. The active principle can also be formulated in microcapsule forms, optionally with one or more carriers or additives. For a local administration, the active ingredient is mixed in an excipient for the preparation of lotions, gels, creams or ointments or it is dissolved in a suitable vehicle. In the pharmaceutical compositions according to the invention, the active principle may also be in the form of inclusion complex in cyclodextrins, their ethers or their esters. It is noted that in relation to this date the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention. Having described the invention as above, the content of the following is claimed as property

Claims (16)

1. Use of the β3-agonist compounds for the preparation of pharmaceutical compositions intended to accelerate the healing of wounds.

2. Use according to claim 1, for the preparation of healing medicaments.

3. Use according to claim 1, for the preparation of pharmaceutical compositions for accelerating the healing of lower limb sores in diabetic mammals.

4. Use according to any of claims 1 to 3, wherein the β3-agonist is a compound of formula (I) wherein x represents hydrogen, a halogen, a trifluoromethyl group or a group (C 1 -C 4) alkyl; R represents hydrogen, a methyl group, unsubstituted or substituted by a carboxy group or 10 lower carbalkoxy and its pharmaceutically acceptable salts.

5. Use in accordance with the 15 claim 4, wherein the β3-agonist is N- [(2R) -7-ethoxycarbonylmethoxy-1,2,3-tetrahydronaphth-2-yl] - (2R) -2- (3-chlorophenyl) - 2- hydroxyethamine or one of its pharmaceutically acceptable salts. twenty

6. Use according to any of claims 1 to 3, wherein the β3-agonist is a compound of formula (II) ~ 2r Ce) alkyl) sulfinyl; benzylsulfinyl; phenylsulfinyl; ((C? -C6) alkyl) sulfonyl; ((C2-C6) alkenyl) sulfonyl; ((C2-C6) alkynyl) sulfonyl; (C3-C8) cycloalkylsulfonyl; ((C3-C8) cycloalkyl (C? C6) alkyl) sulfonyl; benzisulfonyl; phenylsulfonyl; cyano; nitro; amino unsubstituted or substituted by one or two radicals, identical or different, chosen from (C? -C6) alkyl, (C2-C6) alkenyl, 10 (C2-C6) alkynyl, (C3-C8) cycloalkyl, (C3-C8) cycloalkyl (C? -C6) alkyl, benzyl, phenyl; carboxy; Carbalkoxy whose alkyl group is in C? -C6; ((C2-C6) alkenyloxy) carbonyl; ((C? -Ce) alkynyloxy) carbonyl; 15 (C3-C8) cycloalkyloxycarbonyl; ((C3-C8) cycloalkyl (C? -C6) alkoxy) carbonyl; benzyloxycarbonyl; phenoxycarbonyl; carbamoyl unsubstituted or substituted on the amino group by one or two radicals, identical or 20 different, chosen from the groups (Ci- C6) alkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C3-C8) cycloalkyl, (C3-C8) cycloalkyl (C? -Cß) alkyl, benzyl and phenyl; - a group R '' 'chosen between the groups. { C ± - 25 C6) alkyl substituted by a functional group; (C2-C6) alkenyl substituted by a functional group; (C2-C6) alkynyl substituted by a functional group; phenyl (C? -C6) substituted alkyl on the phenyl group by a (C? -C6) alkyl or by a functional group; phenyl (C2-C6) alkenyl substituted on the phenyl group by a (Ci- C6) alkyl or by a functional group; phenyl (C2-C6) alkynyl substituted on the phenyl group by a (Ci-Ce) alkyl or by a functional group; 10 benzyl substituted on the phenyl group by a (C? -C6) alkyl or by a functional group; phenyl, unsubstituted or substituted on the phenol group by a (C? -C6) alkyl or by a functional group; being the functional group such 15 as defined above; - a group OR '' ', SR' '', SO-R '' ', S02-R' ", in which R 'is as defined above for R'; - a group NR '' 'R ° , where R '' 'is as it is 20 defined above and R ° represents hydrogen or is as defined for R '' ', or R' "and R ° form, with the nitrogen to which they are bound, a group selected from the pyrrolidino, piperidino and morpholino; 25 - a group COOR '' 'or a group CO-SR' '' in which R 'is as defined above; - a group CONR '' 'R ° where R' '' is as defined above and R ° represents hydrogen or is as defined for R '' ', or R' "and R ° form, with the nitrogen to which they are bound, a group chosen from the pyrrolidino, piperidino and morpholino groups; - a group S02NR '' 'R ° where R' "is as 10 defined above and R ° represents hydrogen or is as defined above for R 'or R' R ° form, with the nitrogen to which they are bound, a group selected from the pyrrolidino groups, 15 piperidino and morpholino; R "represents - a hydrogen; - a halogen; - a group (C? -C6) alkyl; 20 - a functional group as defined above for R '; - a group OR '' ', R' '' above; a group COOR '' ', R' '' as defined above; 25 - a group CONR '' 'R ° where R' '' is as defined above and R ° represents ai hydrogen or is as defined above for R '' ', or R' '' and R ° form , with the nitrogen to which they are bound, a group chosen from the pyrrolidino, piperidino and morpholino groups; W represents a direct bond or an oxygen atom; X 'represents hydrogen, a (C? -C6) alkyl or a (Ci-Ce) alkylcarbonyl; Y represents hydrogen or a group A'-CH (OH) -CH2-, where A 'is identical to A, but different from benzofuran-2-yl; or X 'and Y, taken together, form a methylene group, optionally substituted by a carbalkoxy group whose alkyl group is in Ci-Ce; an ethylene group, optionally substituted by an oxo group; or a 1,3-propylene group; Z represents hydrogen or a (C? -C6) alkyl; as well as its pharmaceutically acceptable salts.

7. Use according to any of claims 1 to 3, wherein the β3-agonist is a compound of formula (III) which • E represents hydrogen, a group (Ci-Ce) alkyl, a group (C? -C) alkoxy, a phenyl group, a nitro group, a halogen atom or a trifluoromethyl group, L represents hydrogen, a group (C? ~ C4) alkyl, a group (C? -C) alkoxy, a phenyl group, a nitro group, a halogen atom or E and L, together, represent a group -CH = CH-CH = CH- or CH2-CH2-CH2-CH2-, and G represents hydrogen, a chlorine atom, a hydroxy group or an OG 'group where G' represents a (C? -C4) alkyl group unsubstituted or substituted by a hydroxy group, (C? -C4) alkoxy, (C? -C) alkoxycarbonyl, carboxy or (C3-C7) cycloalkyl; a group (C3-C7) cycloalkyl; a (C2-C4) alkanoyl group, such as pharmaceutically acceptable salts thereof. which E represents hydrogen, a group (C? -C6) alkyl, a group (C? -C4) alkoxy, a phenyl group, a nitro group, a halogen atom or a trifluoromethyl group, L represents hydrogen, a group (C? -C4) alkyl, a group (C? ~ C) alkoxy, a phenyl group, a nitro group, a halogen atom or E and L, together, represent a group -CH = CH-CH = CH- or CH2-CH2-CH2-CH2-, and G represents hydrogen, a chlorine atom, a hydroxy group or an OG 'group where G' represents a (C? ~ C4) alkyl group unsubstituted or substituted by a hydroxy group, (C? -C4) alkoxy, (C? -C4) alkoxycarbonyl, carboxy or (C3-C7) cycloalkyl; a group (C3-C7) cycloalkyl; a (C2-C4) alkanoyl group, or pharmaceutically acceptable salts thereof.

8. Use according to claim 7, wherein the β3-agonist is chosen from N- [(6-hydroxy-l, 2,3, '4-tetrahydronaphthalen- (2R) -2-yl) methyl] - (2R ) -2-hydroxy-2- (3-chlorophenyl) ethanamine, N- [(7-methoxy-1, 2, 3, 4-tetrahydronaphthalen- (2R) -2-yl) methyl] - (2R) -2 -hydroxy-2- (3) -chlorophenyl) ethanamine, and its pharmaceutically acceptable salts.

9. Pharmaceutical composition for the prophylaxis and / or treatment of dermal wounds characterized in that it contains a ß3-agonist compound or active ingredient.

10. Pharmaceutical composition according to claim 9, characterized in that it is obtained by using a β3-agonist compound according to any of claims 4 to 6, as an active ingredient. il.

Pharmaceutical composition according to claims 9 or 10, characterized in that it is in the form of a dosage unit containing 0.1 to 400 mg of active ingredient in admixture with a pharmaceutical excipient.

12. Pharmaceutical composition according to claims 9 or 10, characterized in that it is administered by local route.

13. Pharmaceutical composition according to claim 12, characterized in that it contains from 0.01 to 5% of active principle.

14. Pharmaceutical composition according to claim 13, characterized in that it contains from 0.025 to 2.5% of active principle.

15. Pharmaceutical composition according to claim 14, characterized in that it contains from 0.1 to 1% of active principle.

16. Method of prophylaxis and / or treatment of wounds in mammals, characterized in that a prophylactic and / or effective amount of a β3-agonist compound is administered to said mammals in need of said prophylaxis and / or said treatment.