Compounds used in hair removal treatment

Abstract

Described in this disclosure are compounds represented by Formula 1 as illustrated herein. Also described herein are uses, methods, and medicaments related to the treatment of conditions or diseases, such as for hair growth in mammals.

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of U.S. Provisional Patent Application No. 63 / 477,347, filed December 27, 2022, the entire disclosure of which is incorporated herein by reference. [Background technology]

[0002] Hair follicle stem cells (HFSCs) undergo multiple successive periods of quiescence (telogen phase) separated by short periods of proliferation that correlate with the initiation of the hair cycle (telogen-anagen transition). It is well known that proliferation or activation of HFSCs is a prerequisite for progression of the hair cycle. Despite advances in treatment options, baldness and alopecia remain conditions that cannot be successfully treated in many individuals. Some existing treatments are inconvenient for the user, and others require surgical intervention or other invasive procedures. Additional treatments are desirable. Summary of the Invention [Means for solving the problem]

[0003] Some embodiments include compounds of Formula 1 or E / Z isomers thereof. [ka] formula 1 wherein Ar is an optionally substituted aryl, such as an optionally substituted phenyl or an optionally substituted naphthyl.

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

[0005] Certain embodiments include pharmaceutical compositions for hair growth comprising the compounds described herein.

[0006] Certain embodiments include a method of promoting hair growth, comprising administering a compound according to the present invention to an area of ​​mammalian skin where hair growth is intended.

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

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

[0009] Certain embodiments include a method of promoting hair growth, comprising administering to a mammal in need thereof a compound described herein.

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

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

[0012] Unless otherwise specified, any reference herein to a compound by structure, name, or any other means includes pharmaceutically acceptable salts (such as sodium, potassium, and ammonium salts), prodrugs (such as ester prodrugs), solid state alternatives (such as polymorphs, solvates, hydrates, etc.), deuterium-modified forms, Z and E olefin isomers, tautomers, or any other chemical species that may be rapidly converted to a compound described herein under the conditions in which the compound is used as described herein. In certain embodiments, the compound contains deuterium at greater than its natural abundance. In certain embodiments, one or more hydrogen atoms on a compound are replaced with deuterium such that the compound has a deuterium fraction of at least 50%, at least 80%, at least 90%, at least 95%, or at least 99% at that location. E / Z isomers are specifically contemplated for any structure depicted herein.

[0013] Unless otherwise specified, when a compound or chemical structural feature (e.g., alkyl or aryl) is referred to as being "optionally substituted," this includes the feature having no substituents (i.e., unsubstituted) or the feature being "substituted," meaning that the feature has one or more substituents. The term "substituent" is intended to have the broadest meaning known to those skilled in the art and includes a moiety occupying a position normally occupied by one or more hydrogen atoms bonded to the parent compound or parent structural feature. In some embodiments, the substituent may be a common organic moiety known in the art, which may 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 certain embodiments, a substituent group comprises or consists of 0-30, 0-20, 0-10, or 0-5 carbon atoms and 0-30, 0-20, 0-10, or 0-5 heteroatoms, where each heteroatom may independently be N, O, S, P, Si, F, Cl, Br, or I, provided that the substituent group contains one of C, N, O, S, P, Si, F, Cl, Br, or I. Examples of substituent groups include, but are not limited to, compounds having the empirical formula C 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 P0-3 、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 Si 0-3 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 Cl0-3 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 F 0-13 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 O0-4 、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 H 3-15 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 、SH、SR A, NH2, NHR A , N.R. A R B , CF3, CN, a carboxylic acid, an optionally substituted carboxylic ester, or an optionally substituted C 1-6 Alkyl (optionally substituted branched C 2-6 Alkyl or optionally substituted straight chain C 1-6 Alkyl, etc. (optionally substituted branched or straight chain 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 , cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.), alkenyl, alkynyl, heteroalkyl, heteroalkenyl, heteroalkynyl, aryl, heteroaryl, carbocycle, heterocycle, hydroxy, alkoxy, aryloxy, acyl, acyloxy, alkylcarboxylate, thiol, alkylthio, cyano, halo, thiocarbonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, isocyanato, thiocyanato, isothiocyanato, nitro, silyl, sulfenyl, sulfinyl, sulfonyl, haloalkyl, haloalkoxyl, trihalomethanesulfonyl, trihalomethanesulfonamido, and the like.

[0014] For convenience, the term "molecular weight" is used for a portion or part of a molecule, which may not be a complete molecule, to refer to the sum of the molecular weights of the portion or part of the molecule.

[0015] In Formula 1, Ar is an optionally substituted aryl (such as phenyl substituted with 0, 1, 2, 3, 4, or 5 substituents, or naphthyl substituted with 0, 1, 2, 3, 4, 5, 6, or 7 substituents), and the substituents on the aryl (such as phenyl or naphthyl) can be any suitable substituent (F, Cl, Br, I, OH, CN, CF, —SF, C1-6 Alkyl (-CH3, -C2H5, -C3H7, -C4H9, -C5H 11 , -CH 13 etc.), C 1-6 -O-Alkyl (-O-CH3, -O-C2H5, -O-C3H7, -O-C4H9, -O-C5H 11 , -O-CH 13 etc.), or C 1-6 H 3-13 It may also be -O(-C(=O)CH3 or -CH2OCH3, etc.).

[0016] With respect to Formula 1, in certain embodiments, the phenyl group may have 0, 1, 2, 3, 4, or 5 substituents (such as -OCH, -CF, -CH, -OCF, -SCF, -Cl, -SF, etc.). In certain embodiments, Ar is a phenyl having 1 or 2 substituents, which are independently -OCH, -CF, -CH, -OCF, -SCF, Cl, or -SF.

[0017] In certain embodiments, Ar is phenyl having one substituent that is —CF3, —CH3, —OCF3, —SCF3, Cl, or —SF5. In certain embodiments, Ar is phenyl having one substituent that is —OCH3, —CH3, —OCF3, —SCF3, Cl, or —SF5. In certain embodiments, Ar is phenyl having one substituent that is —OCH3, —CF3, —OCF3, —SCF3, Cl, or —SF5. In certain embodiments, Ar is phenyl having one substituent that is —OCH3, —CF3, —CH3, —SCF3, Cl, or —SF5. In certain embodiments, Ar is phenyl having one substituent that is —OCH3, —CF3, —CH3, —OCF3, —Cl, or —SF5. In certain embodiments, Ar is phenyl having one substituent that is —OCH3, —CF3, —CH3, —OCF3, —SCF3, or —SF5. In certain embodiments, Ar is phenyl having one substituent that is —OCH3, —CF3, —CH3, —OCF3, —SCF3, or —SF5. In certain embodiments, Ar is phenyl having one substituent that is —OCH3, —CF3, —CH3, —OCF3, —SCF3, or —SF5. In certain embodiments, Ar is phenyl having one substituent that is -OCH3, -CF3, -CH3, -OCF3, -SCF3, or Cl.

[0018] In certain embodiments, Ar is phenyl having two substituents that are independently —CF3, —CH3, —OCF3, —SCF3, Cl, or —SF5. In certain embodiments, Ar is phenyl having two substituents that are independently —OCH3, —CH3, —OCF3, —SCF3, Cl, or —SF5. In certain embodiments, Ar is phenyl having two substituents that are independently —OCH3, —CF3, —OCF3, —SCF3, Cl, or —SF5. In certain embodiments, Ar is phenyl having two substituents that are independently —OCH3, —CF3, —CH3, —SCF3, Cl, or —SF5. In certain embodiments, Ar is phenyl having two substituents that are independently —OCH3, —CF3, —CH3, —OCF3, —Cl, or —SF5. In certain embodiments, Ar is phenyl having two substituents that are independently —OCH3, —CF3, —CH3, —OCF3, —SCF3, or —SF5. In certain embodiments, Ar is phenyl having two substituents that are independently —OCH3, —CF3, —CH3, —OCF3, —SCF3, or —SF5. In certain embodiments, Ar is phenyl having two substituents that are independently —OCH3, —CF3, —CH3, —OCF3, —SCF3, or —SF5. In certain embodiments, Ar is phenyl having two substituents that are independently -OCH3, -CF3, -CH3, -OCF3, -SCF3, or Cl.

[0019] In certain embodiments, Ar is unsubstituted phenyl. In certain embodiments, Ar is unsubstituted naphthyl.

[0020] In certain embodiments, Ar is [ka] is.

[0021] In certain embodiments, Ar is [ka] is.

[0022] In certain embodiments, Ar is [ka] is.

[0023] In certain embodiments, Ar is [ka] is.

[0024] In certain embodiments, Ar is [ka] is.

[0025] In certain embodiments, Ar is [ka] is.

[0026] In certain embodiments, Ar is [ka] is.

[0027] In certain embodiments, Ar is [ka] is.

[0028] In certain embodiments, Ar is [ka] is.

[0029] In certain embodiments, Ar is [ka] is.

[0030] In certain embodiments, Ar is [ka] is.

[0031] In certain embodiments, Ar is [ka] is.

[0032] In certain embodiments, Ar is [ka] is.

[0033] In certain embodiments, Ar is [ka] is.

[0034] In certain embodiments, Ar is [ka] is.

[0035] In certain embodiments, Ar is [ka] is.

[0036] In certain embodiments, Ar is [ka] is.

[0037] In certain embodiments, Ar is [ka] is.

[0038] In certain embodiments, Ar is [ka] isn't it.

[0039] In certain embodiments, Ar is [ka] isn't it.

[0040] In certain embodiments, Ar is [ka] isn't it.

[0041] In certain embodiments, Ar is [ka] isn't it.

[0042] In certain embodiments, Ar is [ka] isn't it.

[0043] In certain embodiments, Ar is [ka] isn't it.

[0044] In certain embodiments, Ar is [ka] isn't it.

[0045] In certain embodiments, Ar is [ka] isn't it.

[0046] In certain embodiments, Ar is [ka] isn't it.

[0047] In certain embodiments, Ar is [ka] isn't it.

[0048] In certain embodiments, Ar is [ka] isn't it.

[0049] In certain embodiments, Ar is [ka] isn't it.

[0050] In certain embodiments, Ar is [ka] isn't it.

[0051] In certain embodiments, Ar is [ka] isn't it.

[0052] In certain embodiments, Ar is [ka] isn't it.

[0053] In certain embodiments, Ar is [ka] isn't it.

[0054] In certain embodiments, Ar is [ka] isn't it.

[0055] In certain embodiments, Ar is [ka] isn't it.

[0056] In certain embodiments, the compound is [ka] is.

[0057] In certain embodiments, the compound is [ka] is.

[0058] In certain embodiments, the compound is [ka] isn't it.

[0059] In certain embodiments, the compound is [ka] is.

[0060] In certain embodiments, the compound is [ka] is.

[0061] In certain embodiments, the compound is [ka] is.

[0062] In certain embodiments, the compound is [ka] is.

[0063] In certain embodiments, the compound is [ka] is.

[0064] In certain embodiments, the compound is [ka] is.

[0065] In certain embodiments, the compound is [ka] is.

[0066] In certain embodiments, the compound is [ka] is.

[0067] In certain embodiments, the compound is [ka] is.

[0068] In certain embodiments, the compound is [ka] is.

[0069] In certain embodiments, the compound is [ka] is.

[0070] In certain embodiments, the compound is [ka] is.

[0071] In certain embodiments, the compound is [ka] is.

[0072] In certain embodiments, the compound is [ka] is.

[0073] In certain embodiments, the compound is [ka] is.

[0074] In certain embodiments, the compound is [ka] isn't it.

[0075] The compounds described herein are useful for promoting hair growth. For example, the compounds described herein may be administered to the area of ​​mammalian skin where hair growth is desired.

[0076] In certain aspects, compounds of the present disclosure are mitochondrial pyruvate oxidation (MPO) inhibitors. In certain embodiments, compounds described herein can inhibit the mitochondrial pyruvate carrier (MPC). In certain embodiments, the MPO inhibitor is an MPC inhibitor. In certain aspects, inhibition of intracellular MPO has the effect of enhancing intracellular lactate production and / or enhancing intracellular lactate dehydrogenase (LDH) activity, and promoting hair growth. In certain aspects, the present disclosure provides methods for treating a hair growth condition or disorder, such as baldness or alopecia, or promoting hair growth, comprising administering to a patient (e.g., topically, via a pharmaceutical composition formulated for topical application) an MPO inhibitor, such as a compound of the present disclosure. In certain embodiments, the present disclosure provides methods for treating a hair growth condition or disorder, such as baldness or alopecia, or for promoting hair growth, comprising administering to a patient (e.g., topically, in a pharmaceutical composition formulated for topical application) an MPC inhibitor, such as a compound of the present disclosure. In certain embodiments, inhibition of MPO or MPC in cells has the effect of enhancing intracellular lactate production and / or enhancing intracellular LDH activity, and promoting hair growth.

[0077] In this disclosure, the terms "treatment" or "treating" or similar terms (such as "modulate") include the cure, mitigation, treatment, or prevention of disease in humans or other animals, or any other effect considered to be associated with a "drug" as defined in 21 U.S.C. 321(g).

[0078] The following compound was prepared by adapting the method described in PCT / US21 / 39501, filed June 29, 2021, entitled "COMPOSITIONS AND METHODS FOR MODULATING HAIR GROWTH," Attorney Docket Number UCH-22825 (32246.22825) (see Example 5, pages 73-75). The structure was confirmed by FTIR and NMR analysis.

[0079] [ka] (E)-3-(1-benzyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyanoacrylic acid

[0080] [ka] (E)-2-Cyano-3-(1-(naphthalen-2-ylmethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0081] [ka] 3-(1-(3,5-bis(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyanopropanoic acid

[0082] [ka] (E)-2-Cyano-3-(1-(2-methoxy-3-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0083] [ka] (E)-2-Cyano-3-(1-(4-methoxy-3-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0084] [ka] (E)-2-Cyano-3-(1-(3-methoxy-5-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0085] [ka] (E)-2-Cyano-3-(1-(2-methoxy-5-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0086] [ka] (E)-3-(1-(2,4-bis(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyanoacrylic acid

[0087] [ka] (E)-2-Cyano-3-(1-(3-(pentafluorosulfanyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0088] [ka] (E)-2-Cyano-3-(1-(4-(pentafluorosulfanyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0089] [ka] (E)-3-(1-(3-chlorobenzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyanoacrylic acid

[0090] [ka] (E)-2-Cyano-3-(1-(3-methylbenzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0091] [ka] (E)-2-Cyano-3-(1-(2-((trifluoromethyl)thio)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0092] [ka] (E)-3-(1-(2-chloro-3-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyanoacrylic acid

[0093] [ka] (E)-3-(1-(3-chloro-5-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyanoacrylic acid

[0094] [ka] (E)-3-(1-(4-chloro-3-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyanoacrylic acid

[0095] [ka] (E)-2-Cyano-3-(1-(3-(trifluoromethoxy)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acrylic acid

[0096] [ka] (E)-3-(1-(3-chloro-4-(trifluoromethoxy)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-cyanoacrylic acid

[0097] An assay similar to that described in Example 16, pages 43-46 of PCT / US2021 / 039502, filed June 21, 2021, entitled "Composition and Methods for Modulating Hair Growth," Attorney Docket Number UCH-28325, was performed for several of the compounds described herein. IC for inhibition of mitochondrial oxidation for test compounds. 50 was less than 1 μM, and in some cases less than 100 nM.

[0098] Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and the like, used in the specification and claims should be understood to be modified in all instances 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, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

[0099] As used in the context of describing the present invention (particularly in the context of the appended claims), the singular references "a," "the," and "the" should be construed to cover both the singular and the plural, unless otherwise specified herein and clearly contradicted. All methods described herein may be performed in any suitable order, unless otherwise specified herein and clearly contradicted. The use of any and all examples or exemplary language (e.g., "e.g., "etc.") presented herein is intended merely to more clearly illustrate the present invention and does not impose limitations on the scope of the claims. No language in the specification should be construed as referring to any non-claimed element essential to the practice of the invention.

[0100] Sets of alternative elements or embodiments described herein are not to be construed as limitations. The members of each set may be referred to and claimed individually, or in any combination with other members of the set or other elements herein. One or more members of a set may be added to, or deleted from, a set for reasons of convenience and / or patentability.

[0101] Several embodiments are described herein, including the best modes known to the inventors for carrying out the invention. Of course, variations on these described embodiments will be apparent to those skilled in the art in light of the foregoing description. The inventors expect that those skilled in the art will adopt such variations as appropriate, and intend that the invention be practiced otherwise than as specifically described herein. Accordingly, the claims include all modifications and equivalents of the claimed subject matter as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is contemplated unless otherwise specified herein and clearly contradicted.

[0102] Finally, it is to be understood that the embodiments described herein are illustrative of the principles of the claimed invention. Other variations that may be employed are within the scope of the present invention. Thus, for example, but not by way of limitation, alternative embodiments may be utilized in accordance with the teachings herein. Accordingly, the claims should not be limited to the precise embodiments shown and described.

[0103] [Note] [Appendix 1] A compound represented by the following formula: or a pharmaceutically acceptable salt thereof. [ka] wherein Ar is an optionally substituted aryl.

[0104] [Appendix 2] [ka] Attachment 1: The compound of claim 1,

[0105] [Appendix 3] [ka] Attachment 1: The compound of claim 1,

[0106] [Appendix 4] [ka] Attachment 1: The compound of claim 1,

[0107] [Appendix 5] [ka] Attachment 1: The compound of claim 1,

[0108] [Appendix 6] [ka] Attachment 1: The compound of claim 1,

[0109] [Appendix 7] [ka] Attachment 1: The compound of claim 1,

[0110] [Appendix 8] [ka] Attachment 1: The compound of claim 1,

[0111] [Appendix 9] [ka] Attachment 1: The compound of claim 1,

[0112] [Appendix 10] [ka] Attachment 1: The compound of claim 1,

[0113] [Appendix 11] [ka] Attachment 1: The compound of claim 1,

[0114] [Appendix 12] [ka] Attachment 1: The compound of claim 1,

[0115] [Appendix 13] [ka] Attachment 1: The compound of claim 1,

[0116] [Appendix 14] [ka] Attachment 1: The compound of claim 1,

[0117] [Appendix 15] [ka] Attachment 1: The compound of claim 1,

[0118] [Appendix 16] [ka] Attachment 1: The compound of claim 1,

[0119] [Appendix 17] [ka] Attachment 1: The compound of claim 1,

[0120] [Appendix 18] [ka] Attachment 1: The compound of claim 1,

[0121] [Appendix 19] A compound represented by the following formula: or a pharmaceutically acceptable salt thereof. [ka]

[0122] [Appendix 20] 20. A pharmaceutical composition comprising a compound according to any one of claims 1 to 19.

[0123] [Appendix 21] A pharmaceutical composition for hair growth comprising a compound according to any one of claims 1 to 19.

[0124] [Appendix 22] 20. A method of growing hair, comprising administering a compound according to any one of claims 1 to 19 to the area of ​​mammalian skin where hair growth is intended.

[0125] [Appendix 23] 20. Use of a compound according to any one of claims 1 to 19 in the manufacture of a medicament for hair growth.

[0126] [Appendix 24] 20. A method of promoting hair growth, comprising administering to a mammal in need thereof a compound of any one of claims 1 to 19.

[0127] [Appendix 25] 20. A method for treating a disorder affecting hair growth comprising administering to a mammal in need thereof a compound of any one of claims 1 to 19.

[0128] [Appendix 26] 26. The method of claim 25, wherein the disorder is alopecia or baldness.

[0129] [Appendix 27] The compounds exhibit an IC of less than 1 μM for inhibiting mitochondrial oxidation. 50 26. The method of claim 25, having a value.

[0130] [Appendix 28] The compounds exhibit an IC50 inhibitory effect on mitochondrial oxidation of less than 100 nM. 50 26. The method of claim 25, having a value.

[0131] [Appendix 29] 20. A kit comprising a compound of any one of claims 1 to 19 and a label with instructions for administering the compound to promote hair growth.

Claims

1. A compound represented by the following formula: or a pharmaceutically acceptable salt thereof. 【Chemistry 1】 wherein Ar is an optionally substituted aryl. 【Request Item 2】 【Chemistry 2】 2. The compound of claim 1, wherein: 【Request Item 3】 【Chemistry 3】 2. The compound of claim 1, wherein: 【Request Item 4】 【Chemistry 4】 2. The compound of claim 1, wherein: 【Request Item 5】 【Chemistry 5】 2. The compound of claim 1, wherein: 【Request Item 6】 【Transformation 6】 2. The compound of claim 1, wherein: 【Request Item 7】 【Chemistry 7】 2. The compound of claim 1, wherein: 【Request Item 8】 【Transformation 8】 2. The compound of claim 1, wherein: 【Request Item 9】 【Chemistry 9】 2. The compound of claim 1, wherein: 【Request Item 10】 【Chemistry 10】 2. The compound of claim 1, wherein: 【Request Item 11】 【Chemistry 11】 2. The compound of claim 1, wherein: 【Request Item 12】 【Chemistry 12】 2. The compound of claim 1, wherein: 【Request Item 13】 【Chemistry 13】 2. The compound of claim 1, wherein: 【Request Item 14】 【Chemistry 14】 2. The compound of claim 1, wherein: 【Request Item 15】 【Chemistry 15】 2. The compound of claim 1, wherein: 【Request Item 16】 【Chemistry 16】 2. The compound of claim 1, wherein: 【Request Item 17】 【Chemistry 17】 2. The compound of claim 1, wherein: 【Request Item 18】 【Chemistry 18】 2. The compound of claim 1, wherein:

19. A compound represented by the following formula: or a pharmaceutically acceptable salt thereof. 【Chemistry 19】

20. 20. A pharmaceutical composition comprising a compound according to any one of claims 1 to 19.

21. A pharmaceutical composition for hair growth comprising a compound according to any one of claims 1 to 19.

22. 20. A method for promoting hair growth, comprising administering a compound according to any one of claims 1 to 19 to the area of ​​mammalian skin where hair growth is intended.

23. 20. Use of a compound according to any one of claims 1 to 19 in the manufacture of a medicament for hair growth.

24. 20. A method for promoting hair growth, comprising administering to a mammal in need thereof a compound of any one of claims 1 to 19.

25. 20. A method for treating a disorder affecting hair growth, comprising administering to a mammal in need thereof a compound of any one of claims 1 to 19.

26. 26. The method of claim 25, wherein the disorder is alopecia or baldness.

27. The compounds exhibit an IC inhibition of mitochondrial oxidation of less than 1 μM ５０ 26. The method of claim 25, wherein the value

28. The compounds exhibit an IC inhibition of mitochondrial oxidation of less than 100 nM ５０ 26. The method of claim 25, wherein the value

29. 20. A kit comprising a compound of any one of claims 1 to 19 and a label with instructions for administering the compound for hair growth.

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