Compounds for the treatment of hair loss

Abstract

Compounds of Formula 1 depicted herein are described in the present disclosure. Also described herein are uses, methods, and medicaments relating to the treatment of conditions or disorders, such as mammalian hair growth. TIFF2025502850000026.tif54166

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims priority to U.S. Provisional Patent Application No. 63 / 294,775, filed December 29, 2021, the entire contents of which are expressly incorporated by reference. [Background technology]

[0002] Hair follicle stem cells (HFSCs) undergo repeated periods of quiescence (telogen) punctuated by short periods of proliferation that correlate with the initiation of the hair cycle (the transition from telogen to anagen). It is well known that HFSC proliferation or activation is a prerequisite for the progression of the hair cycle. Despite advances in treatment options, baldness and alopecia remain unsuccessfully treatable conditions for many individuals. Some of the existing treatments are inconvenient for users, and others require surgical intervention or invasive procedures. Further therapies are needed. Summary of the Invention [Means for solving the problem]

[0003] Some embodiments are represented by Formula 1: [ka] or an E / Z isomer thereof, where Ph is an optionally substituted aryl, such as an optionally substituted phenyl, or an optionally substituted heteroaryl.

[0004] Some embodiments include pharmaceutical compositions comprising the compounds described herein, in some embodiments, the pharmaceutical compositions are for treating a disease or disorder, such as a disease or disorder that affects or is related to hair growth.

[0005] Some embodiments include pharmaceutical compositions for hair growth comprising a compound described herein.

[0006] Some embodiments include a method of growing hair comprising administering a compound described herein to an area of ​​mammalian skin where hair growth is intended.

[0007] Some embodiments include the use of a compound described herein in the manufacture of a medicament for hair growth.

[0008] Some embodiments include the use of a compound described herein in the manufacture of a medicament for treating a disease or disorder.

[0009] Some embodiments include a method of growing hair comprising administering a compound described herein to a mammal in need of hair growth.

[0010] Some embodiments include a method of treating a disease or disorder, such as a disorder affecting hair growth, comprising administering a compound described herein to a mammal in need of treatment. In some embodiments, the disorder is alopecia or baldness.

[0011] Some embodiments include kits that include a compound described herein and a label with instructions for administering the compound for a use described herein, such as for promoting hair growth. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Unless otherwise indicated, any reference herein to a compound by structure, name, or other means includes pharma- ceutically acceptable salts, such as sodium salts, potassium salts, ammonium salts, and the like; prodrugs, such as ester prodrugs; alternative solid forms, such as polymorphs, solvates, hydrates, and the like; deuterium-modified forms; Z and E olefin isomers; tautomers; or any other species that can be readily converted to the compounds described herein under the conditions in which the compounds are used as described herein. In some embodiments, the compounds contain more deuterium than naturally occurring. In some embodiments, one or more hydrogen atoms on the compounds are replaced with deuterium, and the replacement positions with deuterium are at least 50%, at least 80%, at least 90%, at least 95%, or at least 99% of the compounds. The E / Z isomers of the structures depicted herein are specifically contemplated.

[0013] Unless otherwise indicated, when a compound or chemical structure feature (such as an alkyl or aryl) is referred to as being "optionally substituted," it includes the "substituted" feature, meaning a feature that has no substituents (i.e., is not substituted) or a feature that has one or more substituents. The term "substituent" has its broadest meaning known to those of skill in the art and includes a moiety that occupies a site normally occupied by one or more hydrogen atoms attached to the parent compound or structural feature. In some embodiments, the substituent can be a conventional organic moiety known in the art and can have a molecular weight (e.g., the sum of the atomic weights of the atoms of the substituent) of about 15 g / mol to about 50 g / mol, about 15 g / mol to about 100 g / mol, about 15 g / mol to about 150 g / mol, about 15 g / mol to about 200 g / mol, about 15 g / mol to about 300 g / mol, or about 15 g / mol to about 500 g / mol. In some embodiments, the substituents include or consist of 0-30, 0-20, 0-10, or 0-5 carbon atoms; and 0-30, 0-20, 0-10, or 0-5 heteroatoms, each of which may independently be N, O, S, P, Si, F, Cl, Br, or I; with the proviso that the substituents contain one C, N, O, S, P, Si, F, Cl, Br, or I atom. Examples of the substituents include, but are not limited to, those having the empirical formula:1-12 H 3-29 O 0-4 N 0-4 S 0-4 F 0-25 Cl 0-5 Si 0-3 P 0-3 、C 0-12 H 0-29 O 1-4 N 0-4 S 0-4 F 0-25 Cl 0-5 Si 0-3 P 0-3 、C 0-12 H 0-29 O 0-4 N 1-4 S 0-4 F 0-25 Cl 0-5 Si 0-3 P 0-3 、C 0-12 H 0-29 O 0-4 N 0-4 S 1-4 F 0-25 Cl 0-5 Si 0-3 P 0-3 、C 0-12 H 0-29 O 0-4 N 0-4 S 0-4 F 1-25 Cl 0-5 Si 0-3 P 0-3 、C 0-12 H 0-29 O 0-4 N 0-4 S 0-4 F 0-25 Cl 1-5 Si 0-3 P 0-3 、C 0-12 H 0-29 O 0-4 N 0-4 S 0-4 F 0-25 Cl 0-5 Si 1-3 P 0-3 、C 0-12 H 0-29 O 0-4 N 0-4 S 0-4 F 0-25 Cl 0-5 Si0-3 P 1-3 、C 1-6 H 3-16 O 0-4 N 0-4 S 0-4 F 0-13 Cl 0-3 Si 0-3 P 0-3 、C 0-6 H 0-16 O 1-4 N 0-4 S 0-4 F 0-13 Cl 0-3 Si 0-3 P 0-3 、C 0-6 H 0-17 O 0-4 N 1-4 S 0-4 F 0-13 Cl 0-3 Si 0-3 P 0-3 、C 0-6 H 0-17 O 0-4 N 0-4 S 1-4 F 0-13 Cl 0-3 Si 0-3 P 0-3 、C 0-6 H 0-17 O 0-4 N 0-4 S 0-4 F 1-13 Cl 0-3 Si 0-3 P 0-3 、C 0-6 H 0-17 O 0-4 N 0-4 S 0-4 F 0-13 Cl 1-3 Si 0-3 P 0-3 、C 0-6 H 0-17 O 0-4 N 0-4 S 0-4 F 0-13 Cl 0-3 Si 1-3 P 0-3 、C 0-6 H 0-17 O 0-4 N 0-4 S 0-4 F0-13 Cl 0-3 Si 0-3 P 1-3 、C 1-12 H 3-29 O 0-4 N 0-4 S 0-4 F 0-25 Cl 0-5 P 0-3 、C 1-12 H 3-27 O 0-4 N 0-2 S 0-2 F 0-25 Cl 0-5 P 0-1 、C 1-12 H 3-27 O 0-4 N 0-2 、C 1-12 H 3-25 O 0-4 、C 1-12 H 3-27 N 0-2 、C 1-9 H 3-21 O 0-4 N 0-2 S 0-2 F 0-19 Cl 0-5 P 0-1 、C 1-9 H 3-19 F 0-19 、C 1-9 H 3-21 O 0-4 N 0-2 、C 1-9 H 3-19 O 0-4 、C 1-9 H 3-21 N 0-2 、C 1-6 H 3-15 O 0-3 N 0-2 S 0-2 F 0-13 Cl 0-5 P 0-1 、C 1-6 H 3-13 F 0-13 、C 1-6 H 3-15 O 0-4 N 0-2 、C 1-6 H 3-13 O 0-4 、C 1-6 H3-15 N 0-2 , C 1-3 H 3-9 O 0-3 N 0-2 S 0-2 F 0-13 Cl 0-5 P 0-1 , C 1-3 H 3-7 F 0-7 , C 1-3 H 3-9 O 0-3 N 0-2 , C 1-3 H 3-7 O 0-3 , C 1-3 H 3-9 N 0-2 , F, Cl, Br, I, OH, OR A , S.H., S.R. A , NH2, NHR A , N.R. A R B , CF3, CN, carboxylic acid, optionally substituted carboxylic acid ester; or optionally substituted branched or linear C 1-3 Alkyl (e.g., -CH3, -C2H5, -C3H7), optionally substituted branched, straight chain or cyclic C 3-6 Alkyl (e.g., -C3H7, -C4H9, -C5H 11 , -CH 13 Optionally substituted branched C, including cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. 2-6 Alkyl or optionally substituted straight chain C 1-6 Optionally substituted C such as alkyl 1-6Compounds represented by the following formulae include alkyl; alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, carbocyclic ring, heterocyclic ring, hydroxy, alkoxy, aryloxy, acyl, acyloxy, alkylcarboxylate, thiol, alkylthio, cyano, halo, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amide, N-amide, S-sulfonamide, N-sulfonamide, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxyl, trihalomethanesulfonyl, trihalomethanesulfonamide, and the like.

[0014] For convenience, the term "molecular weight" is used in reference to a part or portion of a molecule, even if not a complete molecule, and refers to the sum of the atomic weights of the atoms in the part or portion of the molecule.

[0015] With respect to formula 1, Ph is 0, 1, 2, 3, 4, or 5 of F, Cl, Br, I, OH, CN, CF3, C 1-6 Alkyl (-CH3, -C2H5, -C3H7, -C4H9, -C5H 11 , -CH 13 etc.), or C 1-6 H 3-13 It is an optionally substituted aryl, such as phenyl, such as phenyl substituted with a substituent such as O(-C(=O)CH3 or -CH2OCH3, etc.), or an optionally substituted heteroaryl.

[0016] In some embodiments, Ph is phenyl substituted with 1, 2, 3, 4, or 5 trifluoromethyl groups. In some embodiments, Ph is trifluoromethylphenyl.

[0017] In some embodiments, Ph is [ka] It is.

[0018] In some embodiments, the Ph is [ka] It is.

[0019] In some embodiments, the Ph is [ka] It is.

[0020] In some embodiments, the Ph is [ka] It is.

[0021] Some embodiments include the compounds: [ka] Includes.

[0022] Some embodiments include the compounds: [ka] Includes.

[0023] Some embodiments include the compounds: [ka] Includes.

[0024] Some embodiments include the compounds: [ka] Includes.

[0025] The compounds described herein are useful for hair growth. For example, certain compounds described herein can be administered to the skin of a mammal in areas where hair growth is intended.

[0026] In some aspects, the compounds of the present disclosure are mitochondrial pyruvate oxidation (MPO) inhibitors. In some embodiments, the compounds described herein may inhibit mitochondrial pyruvate carrier (MPC). In some embodiments, the MPO inhibitor is an MPC inhibitor. In some aspects, inhibition of MPO in cells enhances the production of lactic acid in cells and / or enhances the activity of lactate dehydrogenase (LDH) in cells, which has the effect of promoting hair growth. In some aspects, the present disclosure provides a method of promoting hair growth or treating a hair growth condition or disorder, such as baldness or alopecia, comprising administering to a patient (e.g., topically, such as in a pharmaceutical composition formulated for topical application) an MPO inhibitor, such as a compound of the present disclosure. In certain embodiments, the disclosure provides methods of promoting hair growth or treating a hair growth condition or disorder, such as baldness or alopecia, comprising administering to a patient an MPC inhibitor, such as a compound of the disclosure (e.g., topically, such as in a pharmaceutical composition formulated for topical application). In some embodiments, inhibition of MPO or MPC in cells enhances the production of lactic acid and / or enhances the activity of LDH in cells, which has the effect of promoting hair growth.

[0027] For purposes of this disclosure, the terms "treat," "treatment," or similar terms (such as "modulation") include the cure, mitigation, treatment, prevention of disease in humans or other animals, or other effects associated with a "drug" as defined in 21 USC 321(g).

[0028] Some embodiments include pharmaceutical compositions or dosage forms that include an active pharmaceutical ingredient, such as a compound described herein, and polyethylene glycol 400 (PEG400) (such as about 50% PEG400), Transcutol® P (such as about 15% Transcutol® P), ethanol (such as about 25% ethanol), and / or dimethyl sulfoxide (DMSO) (such as about 10% DMSO).

[0029] Some embodiments include pharmaceutical compositions or dosage forms that include an active pharmaceutical ingredient, such as a compound described herein, and PEG400 (such as about 10% PEG400), Transcutol® HP (such as about 20% Transcutol® HP), ethanol (such as about 45% ethanol), and / or water (such as about 25% water).

[0030] Some embodiments include pharmaceutical compositions or dosage forms that include an active pharmaceutical ingredient, such as a compound described herein, and polyethylene glycol (such as about 10% polyethylene glycol), Transcutol® HP (such as about 20% Transcutol® HP), ethanol (such as about 45% ethanol), and / or water (such as about 25% water).

[0031] The compounds shown below were prepared by adapting the synthetic methods described in WO 2019 / 006359 (e.g., Example 1, pages 45 and 52-53).

[0032] Example 1 Several formulations are used to evaluate the solubility of various compounds.Any suitable pharmaceutical formulation may be used for the compound, but the formulations described below are suitable for administering the compound to the hair or scalp of mammals, such as humans.The formulations may be sterilized before application to mammals, such as humans.

[0033] A non-aqueous formulation containing 50% PEG400, 15% Transcutol® P, 25% ethanol, and 10% DMSO was prepared using the following general process: 10 g of PEG400, 3 g of Transcutol® P, 5 g of ethanol, and 2 g of DMSO were added to a clear vial. The mixture was then stirred with a stir bar until homogenous.

[0034] Aqueous formulation 1 containing 10% PEG400, 20% Transcutol® HP, 45% ethanol, and 25% water was prepared using the following general process: To a large amber Pyrex bottle: 1) add 19.98g PEG400, 2) add 40.07g Transcutol® HP, 3) add 90g ethanol, 4) add 50.03g water, 5) stir the mixture at 800 rpm for 30 minutes using a magnetic stir bar.

[0035] Aqueous formulation 2 containing 10% polyethylene glycol, 20% Transcutol® HP, 45% ethanol, and 25% water was prepared using the following general process: To a large amber Pyrex bottle: 1) add 10.03 g polyethylene glycol, 2) add 20.03 g Transcutol® HP, 3) add 44.99 g ethanol, 4) add 25.02 g water, and 5) stir the mixture at 800 rpm for 30 minutes using a magnetic stir bar.

[0036] The solubility of some of the compounds shown below in the formulations indicated is given below.

[0037] [ka]

[0038] (Solubility results) Aqueous Formulation 1: 0.5 mg of reference compound and 9.9996 g of Aqueous Formulation 1 (0.005% w / w) were stirred at 600 RPM for 1 hour. The reference compound remained undissolved after 1 hour. Aqueous Formulation 2: 0.5 mg of reference compound and 10.0006 g of aqueous Formulation 2 (0.005% w / w) were stirred at 600 RPM for 1 hour. The reference compound remained undissolved after 1 hour. Aqueous Formulation 2: 0.5 mg of reference compound and 2000.1 mg of aqueous formulation 2 (0.025% w / w) were stirred at 600 RPM for 1 hour. The reference compound remained undissolved after 1 hour.

[0039] [ka]

[0040] 1 H NMR (500 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.60 (dd, J = 8.0, 1.5 Hz, 1H), 8.57 (d, J = 0.6 Hz, 1H), 8.44 (dd, J = 4.6, 1.5 Hz, 1H), 7.84-7.82 (m, 2H), 7.63-7.59 (m, 2H), 7.50-7.47 (m, 1H), 7.41 (dd, J = 8.0, 4.7 Hz, 1H). 13 C NMR (125 MHz, DMSO-d6) δ 164.5, 147.8, 146.0, 145.8, 137.0, 134.3, 130.0 (2C), 129.5, 128.5, 125.0 (2C), 120.4, 119.5, 118.4, 109.7, 98.1.

[0041] [ka]

[0042] 1H NMR (500 MHz, DMSO-d6) δ 8.66 (s, 1H), 8.63-8.61 (m, 2H), 8.34 (dd, J = 4.6, 1.5 Hz, 1H), 8.02 (dd, J = 7.8, 1.2, 1H), 7.92 (td, J = 7.6, 0.9 Hz, 1H), 7.84 (t, J = 7.7 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.40 (dd, J = 8.0, 4.7 Hz, 1H). 13 C NMR (125 MHz, DMSO-d6) δ 164.4, 149.9, 146.1, 146.0, 136.0, 134.4, 134.4 (d, J = 1.9 Hz), 132.1, 131.1, 129.5, 127.8 (q, J = 4.8 Hz), 127.2 (q, J = 30.5 Hz), 123.5 (q, J = 273.5 Hz), 119.3, 119.1, 118.1, 109.6, 98.5.

[0043] (Solubility results) Non-aqueous formulations: 0.75% w / w Compound 2 dissolved after 1 hour, 1% w / w Compound 2 remained undissolved after 1 hour.

[0044] Aqueous formulation 1: 1.1 mg of compound 2 and 1000 mg of aqueous formulation 1 (0.1% w / w) were stirred at 600 RPM for 1 hour. Compound 2 was dissolved after 1 hour. 2.1 mg of compound 2 and 997.8 mg of aqueous formulation 1 (0.2% w / w) were stirred at 600 RPM for 1 hour. Compound 2 remained undissolved after 1 hour.

[0045] Aqueous formulation 2: 1.0 mg of compound 2 and 1019.1 mg of aqueous formulation 2 (0.1% w / w) were stirred at 600 RPM for 1 hour. Compound 2 was dissolved after 1 hour. 2.0 mg of Compound 2 and 1004.6 mg of aqueous formulation 2 (0.2% w / w) were stirred at 600 RPM for 1 hour. Compound 2 remained undissolved after 1 hour.

[0046] [ka]

[0047] 1 H NMR (500 MHz, DMSO-d6) δ 13.67 (br s, 1H), 8.89 (s, 1H), 8.63 (dd, J = 7.9, 1.5 Hz, 1H), 8.57 (d, J = 0.8, 1H), 8.47 (dd, J = 4.7, 1.6 Hz, 1H), 8.31 (d, J = 0.9 Hz, 1H), 8.18-8.15 (m, 1H), 7.87-7.83 (m, 2H), 7.44 (dd, J = 8.0, 4.7 Hz, 1H). 13 C NMR (125 MHz, DMSO-d6) δ 164.4, 147.8, 146.0, 145.9, 137.6, 134.3, 131.3, 130.5 (q, J = 32.4 Hz), 129.8, 128.9, 124.9 (q, J = 3.8 Hz), 124.2 (q, J = 272.8 Hz), 121.7 (q, J = 4.1 Hz), 120.4, 119.7, 118.2, 110.2, 98.9.

[0048] (Solubility results) Non-aqueous formulations: 0.1% w / w Compound 3 dissolved after 1 hour, 0.2% w / w Compound 3 remained undissolved after 24 hours.

[0049] [ka]

[0050] 1H NMR (500 MHz, DMSO-d6) δ 8.89 (s, 1H), 8.62 (dd, J = 8.0, 1.6 Hz, 1H), 8.57 (d, J = 0.9 Hz, 1H), 8.47 (dd, J = 4.7, 1.6 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.5 Hz, 2H), 7.44 (dd, J = 8.0, 4.7 Hz, 1H). 13 C NMR (125 MHz, DMSO-d6) δ 164.3, 147.7, 145.9, 145.9, 140.3 (d, J = 1.1 Hz), 133.7, 129.8, 128.2 (q, J = 32.2 Hz), 127.2 (q, J = 3.6 Hz, 2C), 125.2 (2C), 124.5 (q, J = 272.3 Hz), 120.6, 119.8, 118.2, 110.4, 99.2.

[0051] (Solubility results) Non-aqueous formulations: Compound 4 at 0.5% w / w dissolved after 1 hour, Compound 4 at 0.75% w / w remained undissolved after 1 hour.

[0052] An assay similar to that described in Example 16, pages 43-46 of PCT / US2021 / 039502, filed June 21, 2021, entitled "Compositions and Methods for Regulating Hair Growth" (except that intact primary keratinocytes were used in this assay) was performed with some of the compounds described herein. Primary neonatal human epidermal keratinocytes (HEKn; Thermo Fisher, C0015C) were cultured in HEKn medium containing EpiLife™ medium (Thermo Fisher, MEPI500CA), human keratinocyte growth supplement (Thermo Fisher, S0015), and Primocin (Fisher Scientific, NC9392943). XF96 microplates (Agilent) were seeded with 8,000 cells per well and the plates were humidified in a cell culture incubator at 37°C, 5% CO2, and 95% air. The medium was changed daily for 6–7 days prior to Seahorse analysis.

[0053] IC for mitochondrial oxidation inhibition for test compounds 50 The values ​​were below 1 μM and in some cases below 100 nM.

[0054] Unless otherwise indicated, all numbers expressing quantities of ingredients, molecular weights, reaction conditions, and the like used in the specification and claims are to be understood in all instances as modified by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the specification and appended claims are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, no attempt is made to limit the application of equivalents to the scope of the claims, and each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0055] The terms "a," "an," "the," and similar references used in the context of describing the present invention (particularly in the context of the claims below) should be construed to cover both the singular and the plural, unless otherwise stated or clearly contradicted by context. All methods described herein may be performed in any suitable order, unless otherwise stated herein or clearly contradicted by context. Any and all examples provided herein, or the use of exemplary language (e.g., "such as"), are intended to better clarify the present invention and do not limit the scope of the claims. Nothing in this specification should be construed as indicating any non-claimed element essential to the practice of the invention.

[0056] Groupings of alternative elements or embodiments disclosed herein are not to be construed as limitations. The members of each group may be referenced and claimed individually or in any combination with other members of the group or other elements found herein. It is anticipated that one or more members of a group may be included in, or deleted from, a group for reasons of convenience or patentability.

[0057] Several embodiments are described herein, including the best mode known to the inventors for carrying out the invention. Of course, variations of these described embodiments will be apparent to those of skill in the art upon reading the foregoing description. The inventors expect those of skill in the art to make appropriate use of such variations, and the inventors intend to practice the invention otherwise than as specifically described herein. Accordingly, the claims include all modifications and equivalents of the subject matter recited in the claims as permitted by applicable law. Moreover, combinations of the above-described elements in all possible variations are contemplated unless otherwise indicated herein or clearly contradicted by context.

[0058] Finally, it should be understood that the embodiments disclosed herein are illustrative of the principles of the claims. Other modifications that may be adopted are within the scope of the claims. Thus, by way of example, and not of limitation, alternative embodiments may be utilized in accordance with the teachings herein. Thus, the scope of the claims should not be limited to the precise embodiments shown and described.

[0059] (Additional Note) (Appendix 1) formula: [ka] or a pharma- ceutically acceptable salt thereof, Ph is optionally substituted phenyl; The compound, or a pharma- ceutically acceptable salt thereof.

[0060] (Appendix 2) The compound described in Appendix 1, wherein Ph is trifluoromethylphenyl.

[0061] (Appendix 3) [ka] or a pharma- ceutically acceptable salt thereof; A compound described in Appendix 1.

[0062] (Appendix 4) [ka] or a pharma- ceutically acceptable salt thereof; A compound described in Appendix 1.

[0063] (Appendix 5) [ka] or a pharma- ceutically acceptable salt thereof; A compound described in Appendix 1.

[0064] (Appendix 6) [ka] or a pharma- ceutically acceptable salt thereof; A compound described in Appendix 1.

[0065] (Appendix 7) A pharmaceutical composition comprising a compound according to any one of claims 1 to 6.

[0066] (Appendix 8) A pharmaceutical composition for promoting hair growth, comprising a compound according to any one of claims 1 to 6.

[0067] (Appendix 9) 13. A method of promoting hair growth comprising administering a compound according to any one of claims 1 to 6 to an area of ​​mammalian skin in which hair growth is intended.

[0068] (Appendix 10) 13. Use of a compound according to any one of claims 1 to 6 in the manufacture of a medicament for promoting hair growth.

[0069] (Appendix 11) 13. A method for promoting hair growth comprising administering to a mammal in need thereof a compound according to any one of claims 1 to 6.

[0070] (Appendix 12) 13. A method of treating a disorder affecting hair growth comprising administering to a mammal in need of such treatment a compound according to any one of claims 1-6.

[0071] (Appendix 13) 13. The method of claim 12, wherein the disorder is alopecia or baldness.

Claims

1. formula: 【Chemistry 1】 or a pharma- ceutically acceptable salt thereof, Ph is optionally substituted phenyl; The compound, or a pharma- ceutically acceptable salt thereof.

2. The compound of claim 1 , wherein Ph is trifluoromethylphenyl. 【Request 3】 【Chemistry 2】 or a pharma- ceutically acceptable salt thereof; The compound of claim 1. 【Request 4】 【Chemical 3】 or a pharma- ceutically acceptable salt thereof; The compound of claim 1. 【Request 5】 【Chemical 4】 or a pharma- ceutically acceptable salt thereof; The compound of claim 1. 【Request 6】 【Chemical 5】 or a pharma- ceutically acceptable salt thereof; The compound of claim 1.

7. A pharmaceutical composition comprising a compound according to any one of claims 1 to 6.

8. A pharmaceutical composition for promoting hair growth comprising a compound according to any one of claims 1 to 6.

9. 10. A method for promoting hair growth comprising administering to the area of ​​mammalian skin in which hair growth is intended a compound according to any one of claims 1 to 6.

10. 10. Use of a compound according to any one of claims 1 to 6 in the manufacture of a medicament for promoting hair growth.

11. A method for promoting hair growth comprising administering to a mammal in need thereof a compound according to any one of claims 1 to 6.

12. 10. A method of treating a disorder affecting hair growth comprising administering to a mammal in need of treatment a compound according to any one of claims 1-6.

13. The method of claim 12, wherein the disorder is alopecia or baldness.

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