Cosmetic Compounds

Abstract

Disclosed herein is a compound of formula (I) or a pharma- ceutically acceptable salt thereof, wherein Y is C 3-11 cycloalkyl, Z is a straight or branched C 1-14 alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, C=O, -O-, -NH-, and -NR-, where R is a straight or branched chain C 1-6 Further disclosed are cosmetic formulations comprising the compounds of formula I, as well as the use of such compounds or formulations as hair care products. TIFF2025502347000034.tif2253

Description

[Technical field]

[0001] The present disclosure relates to compounds and cosmetic formulations and their use as hair care products. Additionally, methods for the treatment of keratinous materials such as hair are disclosed. [Background technology]

[0002] Human hair is highly organized, but complex in structure. It is composed of a hair follicle embedded in the skin and a hair shaft extending from the skin. Hair is typically composed of two or three layers. The outermost layer is the stratum corneum, the middle layer is the cortex, and in some cases there is a central medulla region made of densely packed cells and / or hollow spaces. Human hair is mostly composed of fibrous structures called macrofibrils, each of which is made of microfibrils held together by matrix proteins. Human hair is composed of 65-95% protein by weight, most of which is keratin, a fibrous, helical protein that is particularly rich in the amino acid cysteine, whose thiol groups can form disulfide bridges, adding rigidity and resistance to the entire hair structure.

[0003] There are various treatments for hair, such as bleaching, dyeing, straightening, perming, etc., during which the hair may be over-processed and damaged by the chemicals required to bring about the desired change. For example, some known hair straightening processes consist of treatment with alkaline straighteners. The high pH (9.0-14.0) causes the hair to swell, which allows the alkaline agents to penetrate the hair fiber, where they react with the keratin, causing the breaking and rearrangement of disulfide bridges present in the keratin, making the hair stretch. In addition to chemically induced damage, physical treatments such as frequent and / or high heat or environmental exposure can alter the hair texture and, in many cases, even lead to permanent damage. Summary of the Invention

[0004] It is highly desirable to avoid, minimize, reduce or repair any such damage that occurs during these hair treatment processes, particularly to restore disulfide cross-links, to restore and improve hair quality, strength and texture.

[0005] The object of the present disclosure is to advance the state of the art of hair repair.A further object of the present disclosure is to provide compounds and formulations for use as hair care products, preferably capable of cross-linking thiol moieties.The cross-linked thiol moieties can be formed, for example, by cleavage of disulfide bridges as a result of physical or chemical hair treatment.A further object of the present invention is to enhance the restoration of disulfide bridges using the linkers of the present invention in hair.

[0006] The applicant has developed a thiol-reactive crosslinker that can crosslink thiol moieties and thus mimic disulfide bridges. The crosslinked thiol moieties may result from prior cleavage of disulfide bridges, for example, as a result of physical or chemical hair treatment. By crosslinking thiol moieties, the thiol-reactive crosslinker disclosed herein effectively allows for the restoration of disulfide bridges.

[0007] The thiol-reactive crosslinkers disclosed herein comprise at least one C 3-11 It comprises at least two electrophiles linked by a fragment comprising a cycloalkyl group. The electrophiles may be selected from maleimide, dithiopyridyl, α-halocarbonyl, among others. 3-11 Cycloalkyl is, for example, C 3-11 Bridged bicycloalkyl etc. 3-11 Surprisingly, at least one C is included as part of the fragment that links the electrophile. 3-11 It has been found that the inclusion of a cycloalkyl group enhances the volume and smoothness of hair treated with the thiol-reactive crosslinker.3-11 The cycloalkyl group has a well-defined hydrophobicity that makes the thiol-reactive crosslinker amphiphilic while still being part of the fragment that links the electrophile. 3-11 Cycloalkyl groups are non-invasive and environmentally friendly, thus contributing to enhanced safety and reduced toxicity.

[0008] The present disclosure relates in a first aspect to a compound of formula I, or a pharma- ceutically acceptable salt thereof: [ka] During the ceremony, Y is C 3-11 is cycloalkyl, Z is a straight or branched chain C 1-14 alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, C=O, -O-, -NH-, and -NR-, where R is a straight or branched chain C 1-6 It is an alkyl.

[0009] In some embodiments, the present disclosure relates to a compound of formula II, or a pharma- ceutically acceptable salt thereof: [ka] During the ceremony, Y is C 3-11 is cycloalkyl, L is selected from CH2 and C=O; Z is a straight or branched chain C 1-13 alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a straight or branched chain C 1-6 It is an alkyl.

[0010] In some embodiments of the compound of formula I or II or a pharma- ceutically acceptable salt thereof, Y is C 4-11 Bridged bicycloalkyl etc. 3-11 It is a bicycloalkyl.

[0011] In some embodiments, the present disclosure relates to a compound of formula III or a pharma- ceutically acceptable salt thereof: [ka] Y is C 4-11 is a bicycloalkyl; X is selected from O, NH, and NR, where R is a straight or branched chain C 1-6 is alkyl, Z is a straight or branched chain C 1-12 alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a branched or straight chain C 1-6 It is an alkyl.

[0012] In some embodiments, the present disclosure relates to a compound of formula IV, or a pharma- ceutically acceptable salt thereof: [ka] During the ceremony, Y is C 5-11 is a bridged bicycloalkyl; Z is a straight or branched chain C 1-11 alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a branched or straight chain C 1-6 It is an alkyl.

[0013] In some embodiments, the present disclosure relates to a compound of formula V, or a pharma- ceutically acceptable salt thereof: [ka] During the ceremony, Y is C 5-11 is a bridged bicycloalkyl; G is -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, n is 1 to 4, preferably 2 or 3; m is an integer of 0 to 8, preferably 0 to 3.

[0014] In some embodiments of the compound of formula V, n is 2 or 3. In some embodiments of the compound of formula V, m is 0, 1, 2, or 3.

[0015] In some embodiments of the compound of formula V, Y is bicyclo[1.1.1]pentane, n is 2 or 3, and m is 0, 1, 2, or 3.

[0016] In some embodiments of the compound of formula V, Y is bicyclo[2.2.2]octane, n is 3, and m is 0.

[0017] In some embodiments of the compound of any one of Formulae I-V, Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0018] In a second aspect, the present disclosure relates to a cosmetic formulation comprising at least one compound according to any of the embodiments described herein.

[0019] In some embodiments of the cosmetic formulation, the cosmetic formulation further comprises at least one cosmetic additive selected from the group consisting of surfactants, oil components, emulsifiers, pearlescent waxes, consistency improvers, thickeners, superfatting agents, stabilizers, polymers, silicone compounds, fats, waxes, lecithin, phospholipids, UV protection agents, moisturizers, biogenic agents, antioxidants, deodorants, antiperspirants, antidandruff agents, film formers, bulking agents, insect repellents, self-tanning agents, tyrosine inhibitors (bleaching agents), hydrotropes, solubilizers, preservatives, fragrance oils and dyes, and mixtures thereof.

[0020] In some embodiments of the cosmetic formulation, the cosmetic formulation further comprises a carrier, preferably selected from water, a C(2-6) alcohol, a C(1-10) polyol, and an oil component.

[0021] In a third aspect, the present disclosure relates to a composition or cosmetic formulation according to any of the embodiments described herein for use as a hair care product.

[0022] In a fourth aspect, the present disclosure relates to the use of a compound according to any of the embodiments described herein for the manufacture of a cosmetic formulation, preferably a hair care product.

[0023] In a fifth aspect, the present disclosure relates to a method for the treatment of keratinous materials such as hair, comprising applying to the keratinous material a compound or a cosmetic preparation according to any of the embodiments described herein. The method particularly relates to the cosmetic treatment of keratinous materials such as hair.

[0024] The compounds and cosmetic formulations disclosed herein are suitable for cosmetic applications, in particular for the protection of healthy hair or the improvement of damaged hair. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0025] Detailed Description of the Disclosure In the context of the present disclosure, restoration of disulfide bridges refers to the process of linking two thiol moieties together (it is understood that the term "disulfide bridge" refers to two thiol moieties that are linked using the compounds of the present invention and are not directly linked by -SS- bonds). The thiol moieties may be, for example, part of a keratin protein. The process of linking thiol moieties together may involve the reaction of each thiol with an electrophilic moiety in the crosslinker. The thiol-reactive crosslinkers disclosed herein typically react with two thiol moieties to form a crosslinking unit that links the two thiol moieties together.

[0026] Unless otherwise specified, the following general definitions apply to all compounds of the present disclosure according to the description.

[0027] As used herein, the term "compounds of the disclosure" refers to compounds represented by Formulas I-V (including salts and stereoisomers thereof) and any of the specific examples disclosed herein.

[0028] "Independently of each other" is understood to mean that when a group occurs more than one time in any compound, its definition at each occurrence is independent of any other occurrence.

[0029] In addition, a dashed or wavy line across a bond, or -C 1-4 It is understood that a solid line without a linkage, such as an alkyl, represents the point of attachment of the residue (ie, subformula).

[0030] Additionally, the abbreviations "C" and "N" are understood to represent all possible degrees of saturation that typically do not result in radicals, nitrenes, or carbenes, i.e., N is -NH-, -N=, and TIFF2025502347000007.tif1114, where C is -CH2-, =CH-, and TIFF2025502347000008.tif1214. Also, a substituent R X"C" as an atom in an aromatic or heteroaromatic ring having the formula: =CH-, =CR X In addition, the substituent R X "C" as an atom in an aromatic or heteroaromatic ring not having - is defined as =CH-, and in some cases, TIFF2025502347000009.tif1214. It is understood and known to those skilled in the art that the general rules of valency must be followed.

[0031] The term "saturated" with respect to a ring system refers to a ring that has no double or triple bonds. The term "partially unsaturated" with respect to a ring system refers to a ring that contains at least one double or triple bond, but does not contain an aromatic system.

[0032] In any formula, straight or branched alkyl chains, such as straight or branched C 2-25 Whenever more than one CH2 group of an alkyl is replaced by a heteroatom or heteroatom-containing group, it is understood that two or more CH2 groups are replaced such that immediately adjacent heteroatoms, such as -OO- or -NH-NH-, are avoided. In particular, two or more CH2 groups are intended to be replaced such that the alkyl chain does not contain a peroxide group. The same applies to the selection of general groups defined herein, such as G or Z, which are selected to avoid immediately adjacent heteroatoms, such as -OO- or -NH-NH-.

[0033] "C 3-11 The term "cycloalkyl" refers to a saturated or partially unsaturated alkyl ring system containing 3, 4, 5, 6, 7, 8, 9, 10, or 11 carbon atoms, including monocyclic, fused bicyclic, bridged bicyclic, or spiro bicyclic rings. In some embodiments, "C 3-11 The term "cycloalkyl" refers to a saturated alkyl ring system containing 3, 4, 5, 6, 7, 8, 9, 10, or 11 carbon atoms, including monocyclic, fused bicyclic, bridged bicyclic, or spiro bicyclic ring systems.

[0034] "C 3-11 Examples of "cycloalkyl" include monocyclic compounds such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; bicyclic compounds such as bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, bicyclo[3.2.2]nonane, and bicyclo[3.3.1]nonane; bicyclo[2.1.0]pentane, bicyclo[2.2.0]hexane, and bicyclo[3. fused bicyclic compounds such as bicyclo[3.1.0]hexane, bicyclo[3.2.0]heptane, bicyclo[4.1.0]heptane, bicyclo[4.2.0]octane, bicyclo[4.3.0]nonane, and bicyclo[4.4.0]decane; and spirocyclic compounds such as spiro[2.2]pentane, spiro[2.3]hexane, spiro[3.3]heptane, spiro[3.4]octane, spiro[4.4]nonane, spiro[3.5]nonane, spiro[4.5]decane, and spiro[5.5]undecane.

[0035] In some embodiments, C 3-11 Cycloalkyl is C 4-11 In some embodiments, C 3-11 Cycloalkyl is C 5-11 In some embodiments, C is a bridged bicycloalkyl. 3-11 Cycloalkyl is C 4-11 In some embodiments, C is a fused bicycloalkyl. 3-11 Cycloalkyl is C 5-11 In some embodiments, C is a spirocycloalkyl. 3-11 Cycloalkyl is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0036] "C 3-11A "cycloalkyl" group has two points of attachment. A point of attachment is an atom that forms a covalent bond with another atom to which the group is attached. The two points of attachment may be located on the same or different atoms.

[0037] "C 1-14 Alkyl, C 1-12 Alkyl, C 1-11 Alkyl, and C 1-6 The term "alkyl" refers to a fully saturated branched or unbranched hydrocarbon moiety having the indicated number of carbon atoms. 1-14 Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, neohexyl, heptyl, octyl, nonyl, decyl, dodecyl, and the like. 1-6 Representative examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, or neohexyl. 1-14 Alkyl, C 1-12 Alkyl, C 1-11 Alkyl, and C 1-6 One or more adjacent or non-adjacent CH groups of the alkyl may be independently replaced by one or more groups selected from -O(CH2-O-CH2)-, -(CH2-CH2-O)-, and -(O-CH2-CH2)-, -O-, -NH-, -NR-, where R is a straight or branched chain C 1-6 It is an alkyl.

[0038] Based on the definitions provided throughout this application, one of skill in the art will recognize which combinations are synthetically feasible and practical; for example, typically, combinations of groups that result in several heteroatoms being directly linked to each other, such as -OO-, are not contemplated, but synthetically feasible combinations such as -SN= in isothiazoles are contemplated.

[0039] In a first aspect, the present disclosure relates to a compound of formula I: [ka] During the ceremony, Y is C 3-11 is cycloalkyl, Z is a straight or branched chain C 1-14 alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, and -(O-CH-CH)-, C=O, -O-, -NH-, and -NR-, where R is a straight or branched chain C 1-6 It is an alkyl.

[0040] In some embodiments of the compound of Formula I, Y is C 4-11 In some embodiments of the compound of formula I, Y is C 5-11 In some embodiments of the compound of formula I, Y is C 4-11 In some embodiments of the compound of formula I, Y is C 5-11 It is a spirocycloalkyl.

[0041] In some embodiments of the compound of formula I, Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0042] In some embodiments of the compound of formula II, Z is a straight or branched C 1-14 In some embodiments of the compound of formula II, Z is a straight or branched C alkyl. 1-14alkyl, where one or more CH groups are independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a straight or branched chain C 1-6 It is an alkyl.

[0043] In some embodiments of the compound of Formula I, Z is a straight or branched C 1-14 alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, O-(CH-CH-O)-, -(O-CH-CH)-, C=O, and -O-.

[0044] In some embodiments of the compound of Formula I, Z is a straight or branched C 1-6 alkyl, where one or more CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, and -O-.

[0045] In some embodiments of the compound of Formula I, Z is a straight or branched C 1-8 alkyl, where up to five CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, and -O-.

[0046] In some embodiments, the compound of the invention is a compound of formula II: [ka] During the ceremony, Y is C 3-11 is cycloalkyl, L is selected from CH2 and C=O; Z is a straight or branched chain C 1-13alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a straight or branched chain C 1-6 It is an alkyl.

[0047] In some embodiments of the compound of formula II, Z is a straight or branched C 1-13 In some embodiments of the compound of formula II, Z is a straight or branched C alkyl. 1-13 alkyl, where one or more CH groups are independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a straight or branched chain C 1-6 It is an alkyl.

[0048] In some embodiments of the compound of formula II, L is CH. In some embodiments of the compound of formula II, L is C=O.

[0049] In some embodiments of the compound of Formula II, Y is C 4-11 In some embodiments of the compound of formula II, Y is C 5-11 In some embodiments of the compound of formula II, Y is C 4-11 In some embodiments of the compound of formula II, Y is C 5-11 It is a spirocycloalkyl.

[0050] In some embodiments of the compound of formula II, Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0051] In some embodiments of the compound of Formula II, L is CH and Y is C 4-11 Bicycloalkyl, preferably C 5-11 In some embodiments of the compound of formula II, L is C=O and Y is C 4-11 Bicycloalkyl, preferably C 5-11 It is a bridged bicycloalkyl.

[0052] In some embodiments of the compound of formula II, L is CH2 and Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane. In some embodiments of the compound of formula II, L is C=O and Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0053] In some embodiments of the compound of formula II, Z is a straight or branched C 1-13 alkyl, where one or more CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, and -O-.

[0054] In some embodiments of the compound of formula II, Z is a straight or branched C 1-10 alkyl, where one or more CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, and -O-.

[0055] In some embodiments of the compound of formula II, Z is a straight or branched C1-8 alkyl, where up to five CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, and -O-.

[0056] In some embodiments, the compound of the invention is a compound of formula III: [ka] During the ceremony, Y is C 4-11 is a bicycloalkyl; X is selected from O, NH, and NR, where R is a straight or branched chain C 1-6 is alkyl, Z is a straight or branched chain C 1-12 alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a branched or straight chain C 1-6 It is an alkyl.

[0057] In some embodiments of the compound of Formula III, Z is a straight or branched C 1-12 In some embodiments of the compound of formula III, Z is a straight or branched C alkyl. 1-12 alkyl, where one or more CH groups are independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a branched or straight chain C 1-6 It is an alkyl.

[0058] In some embodiments of the compound of formula III, X is O. In some embodiments of the compound of formula III, X is NH. In some embodiments of the compound of formula III, X is NR, where R is a branched or straight chain C 1-6 It is an alkyl.

[0059] In some embodiments of the compound of Formula III, Y is C 5-11 In some embodiments of the compound of formula III, Y is C 4-11 In some embodiments of the compound of formula III, Y is C 5-11 It is a spirocycloalkyl.

[0060] In some embodiments of the compound of formula III, Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0061] In some embodiments of the compound of Formula III, X is O and Y is C 5-11 In some embodiments of the compound of formula III, X is O and Y is C 4-11 In some embodiments of the compound of formula III, X is O and Y is C 5-11 In some embodiments of the compound of formula III, X is O and Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0062] In some embodiments of the compound of formula III, X is NH and Y is C 5-11 In some embodiments of the compound of formula III, X is NH and Y is C 4-11 In some embodiments of the compound of formula III, X is NH and Y is C 5-11In some embodiments of the compound of formula III, X is NH and Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0063] In some embodiments of the compound of Formula III, Z is a straight or branched C 1-12 alkyl, where one or more CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, and -O-.

[0064] In some embodiments of the compound of formula III, Z is a straight or branched C alkyl, where one or more CH groups are optionally independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-.

[0065] In some embodiments of the compound of Formula III, Z is a straight or branched C 1-8 alkyl, where up to five CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-.

[0066] In some embodiments, the compound of the invention is a compound of formula IV: [ka] During the ceremony, Y is C 5-11 is a bridged bicycloalkyl; Z is a straight or branched chain C 1-11alkyl, where one or more CH groups may be independently replaced by -(CH-O-CH)-, -(CH-CH-O)-, -(O-CH-CH)-, -O-, -NH-, and -NR-, where R is a branched or straight chain C 1-6 It is an alkyl.

[0067] In some embodiments of the compound of formula IV, Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0068] In some embodiments of the compound of formula IV, Z is a straight or branched C 1-11 alkyl, where one or more CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, and -O-.

[0069] In some embodiments of the compound of formula IV, Z is a straight or branched C 1-9 alkyl, where one or more CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-.

[0070] In some embodiments of the compound of formula IIV, Z is a straight or branched C 1-7 alkyl, where up to five CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-.

[0071] In some embodiments of the compound of formula IV, Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, and Z is a straight or branched C 1-9 alkyl, where one or more CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-.

[0072] In some embodiments of the compound of Formula IV, Y is bicyclo[1.1.1]pentane and Z is a straight or branched C 1-9 alkyl, where one or more CH2 groups may be independently replaced by -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-.

[0073] In some embodiments, the compound of the invention is a compound of formula V: [ka] During the ceremony, Y is C 5-11 is a bridged bicycloalkyl; G is -(CH2-O-CH2)-, -(CH2-CH2-O)-, -(O-CH2-CH2)-, n is 1 to 4, preferably 2 or 3; m is an integer of 0 to 8, preferably 0 to 3.

[0074] In some embodiments of the compound of formula V, Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane.

[0075] In some embodiments of the compound of formula V, G is -(CH2-O-CH2)-. In some embodiments of the compound of formula V, G is -(CH2-CH2-O)-. In some embodiments of the compound of formula V, G is -(O-CH2-CH2)-.

[0076] In some embodiments of the compound of formula V, n is 1. In some embodiments of the compound of formula V, n is 2. In some embodiments of the compound of formula V, n is 3. In some embodiments of the compound of formula V, n is 4.

[0077] In some embodiments of the compound of formula V, m is 0. In some embodiments of the compound of formula V, m is 1. In some embodiments of the compound of formula V, m is 2. In some embodiments of the compound of formula V, m is 3. In some embodiments of the compound of formula V, m is 4. In some embodiments of the compound of formula V, m is 5. In some embodiments of the compound of formula V, m is 6. In some embodiments of the compound of formula V, m is 7. In some embodiments of the compound of formula V, m is 8.

[0078] In some embodiments of the compound of formula V, n is 2 and m is 0. In some embodiments of the compound of formula V, n is 2 and m is 1. In some embodiments of the compound of formula V, n is 2 and m is 2. In some embodiments of the compound of formula V, n is 2 and m is 3.

[0079] In some embodiments of the compound of formula V, n is 3 and m is 0. In some embodiments of the compound of formula V, n is 3 and m is 1. In some embodiments of the compound of formula V, n is 3 and m is 2. In some embodiments of the compound of formula V, n is 3 and m is 3.

[0080] In more specific embodiments, the present disclosure relates to the specific examples disclosed in Table 1.

[0081] [Table 1]

[0082] In some embodiments, the disclosure relates to the (S) enantiomer of a compound of any of formulas I-V. In some embodiments, the disclosure relates to the (R) enantiomer of a compound of any of formulas I-V. In some embodiments, the disclosure relates to the racemate of a compound of any of formulas I-V.

[0083] The compounds of the present disclosure may contain one or more asymmetric centers in the molecule. Compounds without a stereochemistry designation should be understood to include all optical isomers (e.g., diastereomers, enantiomers, etc.) in pure or substantially pure form, and mixtures thereof (e.g., racemic mixtures, or mixtures enriched in one enantiomer). It is well known in the art how to prepare such optically active forms (e.g., by resolution of racemates by recrystallization techniques, synthesis from optically active starting materials, chiral synthesis, chromatographic separation using chiral stationary phases, and other methods).

[0084] The compounds may be isotopically labeled compounds, e.g., compounds containing various isotopes of hydrogen, carbon, nitrogen, oxygen. The disclosed compounds may exist as tautomers and mixtures, and individual tautomers are contemplated. In addition, some compounds may exhibit polymorphism.

[0085] The compounds of the present disclosure include free form and its pharmaceutically acceptable salts and stereoisomers. Pharmaceutically acceptable salts include all typical pharmaceutically acceptable salts. The pharmaceutically acceptable salts of the compounds of the present invention can be synthesized from the compounds of the present disclosure that contain a basic or acidic moiety by conventional chemical methods (see, for example, Berge et al, "Pharmaceutical Salts," J. Pharm. ScL, 1977:66:1-19). In addition, the compounds of the present disclosure also include lyophilized compounds and polymorphs of the free form.

[0086] For example, conventional pharma- ceutically acceptable salts for basic compounds include salts derived from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfamic acid, phosphoric acid, nitric acid, and the like, and salts prepared from organic acids such as acetic acid, propionic acid, succinic acid, glycolic acid, stearic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, pamoic acid, maleic acid, hydroxymaleic acid, phenylacetic acid, glutamic acid, benzoic acid, salicylic acid, sulfanilic acid, 2-acetoxybenzoic acid, fumaric acid, toluenesulfonic acid, methanesulfonic acid, ethanedisulfonic acid, oxalic acid, isethionic acid, trifluoroacetic acid, and the like. Conventional pharma- ceutically acceptable salts for acidic compounds include salts derived from inorganic bases such as aluminum, ammonium, calcium, copper, ferric acid, ferrous acid, lithium, magnesium, manganic acid, manganous, potassium, sodium, zinc, and the like. Salts derived from pharma- ceutically acceptable organic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines, and basic ion exchange resins such as arginine, betaine, caffeine, choline, N,N-dibenzylethylenediamine, diethylamine, 2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine, ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine, glucosamine, histidine, hydrabamine, isopropylamine, lysine, methylglucamine, morpholine, piperazine, piperidine, polyamine resins, procaine, purines, theobromine, triethylamine, trimethylamine, tripropylamine, tromethamine, and the like.

[0087] The compounds of the present disclosure may exist in the solid state, i.e., in crystalline form (e.g., polymorphs, i.e., different crystal structures with the same chemical composition but different packing, geometric arrangement) or in amorphous or liquid form (optionally as solvates). It may exist as a mixture thereof in the solid state. In crystalline solvates, solvent molecules are incorporated into the crystal lattice during crystallization. The formation of solvates includes, but is not limited to, non-aqueous solvents such as ethanol, isopropanol, DMSO, acetic acid, ethanolamine, or ethyl acetate, or aqueous solvents such as water (also called "hydrates"). For example, by changing or adjusting the reaction conditions or reagents, different polymorphs may be produced.

[0088] In a further aspect, the present disclosure also provides methods of preparation of compounds of Formulas I-V of the present disclosure.

[0089] In yet another aspect, the present invention further provides a cosmetic formulation comprising an effective amount of one or more of the compounds of the present invention or their pharma-ceutically acceptable salts and a pharma-ceutically acceptable carrier and / or excipient (also called diluent). An excipient is acceptable in the sense that it is compatible with other components of the formulation and is not harmful to its recipient. As used herein, the term "effective amount" refers to the amount of the compound of the present disclosure (by itself or in the form of a cosmetic formulation) that is effective to produce the desired effect of hair restoration.

[0090] Typically, the pH of cosmetic preparations is 3.5 to 6, in particular 4 to 5, at 20° C. The pH can be adjusted, for example, using lactic acid, citric acid, and the like.

[0091] Typically, the concentration of the compounds disclosed herein will be from 0.01% to 5% by weight of the cosmetic formulation, such as from 2% to 4% by weight. In some embodiments, the concentration of the compounds disclosed herein will be from 50 to 130 mmol per liter of cosmetic formulation, particularly from 80 to 100 mmol per liter.

[0092] In some embodiments, the cosmetic formulation comprises a solubilizer, the concentration of which may be, for example, from 5% to 20% by weight of the cosmetic formulation, in particular from 10% to 20% by weight, for example from 15% to 20% by weight.

[0093] In some embodiments, the cosmetic formulation comprises phenoxyethanol at a concentration of 0.1% to 1.7%, particularly 0.7% to 1.1%, for example 0.9%, by weight of the cosmetic formulation.

[0094] In some embodiments, the cosmetic formulation comprises ethylhexylglycerin at a concentration of 0.01% to 0.2%, particularly 0.08% to 0.12%, for example 0.1%, by weight of the cosmetic formulation.

[0095] The phrase "pharmacologically acceptable carrier" as used herein means a pharma- ceutically acceptable material, composition, or vehicle, such as a liquid or solid filler, diluent, excipient, manufacturing aid (e.g., lubricants, talc, magnesium, calcium or zinc stearate, or stearic acid), or solvent encapsulating material involved in carrying or transporting a compound of interest from one organ or part of the body to another. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not harmful to the subject to be treated. Some examples of materials that can serve as pharma- ceutically acceptable carriers include: (1) sugars, such as lactose, glucose, and sucrose; (2) starches, such as corn starch and potato starch; (3) cellulose and its derivatives, such as sodium carboxymethylcellulose, ethylcellulose, and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; (8) excipients, such as cocoa butter and suppository wax; (9) oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil, and soybean oil; and (10) propylene glycol. (11) polyols, such as glycerin, sorbitol, mannitol, and polyethylene glycol; (12) esters, such as ethyl oleate and ethyl laurate; (13) agar; (14) buffers, such as magnesium hydroxide and aluminum hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; (20) pH buffers; (21) polyesters, polycarbonates, and / or polyanhydrides; and (22) other non-toxic compatible materials utilized in cosmetic formulations.

[0096] Such compositions may contain additional components commonly used in cosmetic formulations, such as sodium lauryl sulfate and magnesium stearate, such as wetting agents, emulsifiers, and lubricants, as well as colorants, release agents, coating agents, sweeteners, flavors, fragrances, preservatives and antioxidants, pH adjusters, bulking agents, and additional active agents. Examples of pharmaceutically acceptable antioxidants include (1) water-soluble antioxidants such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, and sodium sulfite, (2) oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), lecithin, propyl gallate, and alpha-tocopherol, and (3) metal chelating agents such as citric acid, ethylenediaminetetraacetic acid (EDTA), sorbitol, tartaric acid, and phosphoric acid.

[0097] Such compositions can be prepared by any method known in the art, for example, by associating active ingredient with one or more carriers and / or excipients.Different compositions and examples of carriers and / or excipients are well known to those skilled in the art and are described in detail in, for example, Remington: The Science and Practice of Pharmacy. Pharmaceutical Press, 2013; Rowe, Sheskey, Quinn: Handbook of Pharmaceutical Excipients. Pharmaceutical Press, 2009.The excipients that can be used to prepare cosmetic formulations can include buffers, stabilizers, surfactants, wetting agents, lubricants, emulsifiers, suspending agents, preservatives, antioxidants, opaquing agents, lubricants, processing aids, colorants, sweeteners, fragrances, flavorings, diluents, and other known additives to provide compositions or formulations suitable for selected administration.

[0098] The cosmetic formulation of the present disclosure may be in any suitable form. In some embodiments, such suitable forms include, but are not limited to, liquids, such as, for example, liquids with low to medium viscosity, such as lotions, milks, mousses, sprays, gels, creams, ointments, pastes, etc. Suitable excipients, such as those listed above, are included or excluded from the dermatological formulation depending on the form of use of the formulation (e.g., lotions, gels, ointments, or creams).

[0099] The liquid form of the compound of the present disclosure includes pharma- ceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active ingredient, the liquid form may contain, for example, water or other solvents, inert diluents commonly used in the art, such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan, and mixtures thereof. In the form of a suspension, the compound may contain, for example, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, and tragacanth, and mixtures thereof.

[0100] In the form of spray, ointment, paste, cream, lotion, gel, solution, the compound can be mixed under sterile conditions with a pharma- ceutically acceptable carrier and with preservatives, buffers, or propellants that may be required.Such ointments, pastes, creams, and gels can contain, in addition to the compound of the present disclosure, excipients such as animal and vegetable oils, oils, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc, zinc oxide, or mixtures thereof.

[0101] In the form of powders and sprays, the compounds of the present disclosure may contain excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicate, and polyamide powder, or mixtures of these substances. Sprays can additionally contain common propellants such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.

[0102] In some embodiments, the cosmetic formulation is a hair care product, which includes products in the form of shampoos, conditioners, hair masks, hair rinses, hair sprays, hair foams, hair mousses, hair gels, hair tonics, and the like.

[0103] It will be understood that all compositions and preparations contemplated must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms, such as bacteria and fungi.

[0104] The amount of the compound of the present disclosure in the cosmetic formulation of the present disclosure can be adjusted to obtain an amount of the compound of the present disclosure that is effective to achieve the desired cosmetic response for a particular person, composition, and method of administration without being harmful to the person. The amount selected depends on various factors, including the nature of the particular compound of the present disclosure used, the route of administration, the time of administration, the duration of treatment, other compounds and / or materials used in combination with the particular compound, the age, sex, weight, condition, general health, and past medical history of the person being treated, and similar factors well known in the medical field.

[0105] Typically, the appropriate amount of the compound of the present disclosure will be the minimum amount of the compound effective to produce the desired effect. Such effective dosage will generally depend on the factors mentioned above. In the form of a shampoo, the amount of the cosmetic preparation applied per treatment can be, for example, 1 g to 10 g. In the form of a conditioner and / or hair mask, the amount of the cosmetic preparation applied per treatment can be, for example, 1 g to 10 g. In the form of a leave-on conditioner or leave-on mask, the amount of the cosmetic preparation applied per treatment can be, for example, 0.1 g to 7 g.

[0106] All of the compounds, compositions, formulations, and / or methods disclosed and claimed herein can be made and carried out without undue experimentation in light of the present disclosure.It will be clear to those skilled in the art that modifications can be applied to the present disclosure without departing from the scope of the present disclosure.The examples provided herein are intended to be illustrative and are not exhaustive, and therefore the illustrated examples should not be considered as limiting the present disclosure in any way. EXAMPLES

[0107] material: N-Fmoc-cysteine ​​(hereafter C1) or N-Cbz-cysteine ​​(hereafter C2) were obtained by reduction of their cysteine ​​counterparts by methods known in the literature. Adv. Syn. Catal., 2020, 362, 5093-5104. DOI: 10.1002 / adsc.202000716. "OLAPLEX® N O "Olaplex 1.0 Intensive Bond Building Hair Treatment" is a commercial product that contains an active agent, water, phenoxyethanol, and sodium benzoate. The active agent is hereinafter referred to as "Olaplex active agent" or "Reference compound #2."

[0108] Example 1: Synthesis of Reference Compounds

[0109] [ka]

[0110] (a) Reference compound #1 To a solution of maleic anhydride (25.0 g, 5.00 Eq, 260 mol) in acetic acid (200 mL), 3,3'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(propan-1-amine) (12.0 g, 1.00 Eq, 52.0 mmol) was added and refluxed for 2 h. The solution was cooled to room temperature. Toluene (50 mL) was then added. The mixture was concentrated under reduced pressure to approximately 100 mL. It was filtered through a silica plug (~3 cm) and washed with a 1 / 1 mixture of EtOAc / cyclohexane. The crude material was purified by column chromatography (silica gel, EtOAc in cyclohexane, gradient 0-80% EtOAc) to give reference compound #1 (3.4 g, 17%) as a yellowish oil. 1 H NMR (400MHz, DMSO) δ6.99 (s, 4H), 3.50-3.40 (m, 12H), 3.37 (t, J=6.1Hz, 4H), 1.70 (m, 4H). LC-MS(ESI+), [M+H] + =381.

[0111] (b) Reference compound #2 = Olaplex activator The activator used as test substrate #2 in Example 8, "Olaplex activator," has the following structure:

[0112] [ka] Olaplex activators were synthesized by reacting two equivalents of the corresponding acid with one equivalent of the corresponding diamine.

[0113] Example 2: Synthesis of Compound 1 (SPC-TB-0001) Scheme Method 1-A

[0114] [ka]

[0115] (a) Bis-alcohol (ii) To a suspension of dimethylbicyclo[1.1.1]pentane-1,3-dicarboxylate (25.38 g, 1.00 Eq, 137.8 mmol) in anhydrous THF (551 mL) at 0° C. under nitrogen, a 2 M solution of LiAlH4 in THF (151.6 mL, 2.20 Eq, 303.1 mmol) was added dropwise. The temperature in the flask was kept below 10° C. during the addition. The resulting solution was stirred at room temperature for 16 h. After completion, the solution was quenched by performing a Fieser workup. The crude material (19.08 g, quantitative, yield) was isolated as a colorless oil, which solidified after some time. It was used as is without purification. 1 H NMR (400MHz, DMSO) δ4.39(t, J=5.6Hz, 2H), 3.35(d, J=5.6Hz, 4H), 1.45(s, 6H)

[0116] (b) Bis-cyano intermediate (iii) To a solution of bicyclo[1.1.1]pentane-1,3-diyldimethanol (6.60 g, 1.00 Eq, 51.0 mmol) in toluene (40.0 mL) was added 40% aqueous tetrabutylammonium hydroxide (40.0 mL, 1.20 Eq, 61.0 mmol) at room temperature. Then acrylonitrile (7.90 mL, 4.00 Eq, 210 mmol) was added dropwise and the biphasic mixture was stirred vigorously at room temperature for 4 h. Then the phases were separated and the aqueous phase was extracted with EtOAc (3×). The combined organic phases were washed with brine (1×), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, EtOAc in cyclohexane, gradient 0-100% EtOAc) to give the title compound (9.2 g, 76%) as a colorless oil. 1H NMR (400MHz, DMSO) δ3.57(t, J=6.0Hz, 4H), 3.43(s, 4H), 2.73(t, J=6.0Hz, 4H), 1.62(s, 6H). TLC-MS, [M+H] + =235

[0117] (c) Bis-Boc-protected amine intermediate (iv) To a solution of 3,3'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))dipropanenitrile (413 mg, 1.00 Eq, 1.76 mmol) and nickel(II) chloride-hexaaquo complex (545 mg, 1.30 Eq, 2.29 mmol) in MeOH (35 mL) at 0 °C was added NaBH4 (533 mg, 8.00 Eq, 14.1 mmol) in small portions. The black reaction mixture was stirred for 30 min, after which Boc-anhydride (1.15 g, 3.00 Eq, 5.29 mmol) was added and allowed to warm to room temperature for 14 h. The reaction was quenched with brine (1 mL), methanol was removed under reduced pressure, and the residue was retaken up in diethyl ether (150 mL). The mixture was filtered through a plug of Celite (2 cm) and washed with diethyl ether (3×50 mL). The organic phase was washed with water (100 mL) and brine (100 mL) and concentrated under reduced pressure. The crude material (550 mg, 70%) was obtained as a yellow oil and was used directly without purification. Note: The product contained Boc-anhydride. 1 H NMR (400MHz, DMSO) δ6.72(s, 2H), 3.37(t, J=6.3Hz, 4H), 3.33(s, 4H), 2.96(td, J=7.0, 5.7Hz, 4H), 1.58(s, 6H), 1.37(m, 21H). TLC-MS, [M+H] + =443

[0118] (d) Bis-amine hydrochloride - intermediate (v) Di-tert-butyl (((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(propane-3.1-diyl))dicarbamate (550 mg, 1.00 Eq, 1.24 mmol) was dissolved in a 4-M HCl solution in dioxane (3.1 mL, 10.0 Eq, 1.2.4 mmol) and stirred at room temperature for 16 h. The reaction mixture was concentrated. The residue was triturated with diethyl ether (5 mL). The title compound was obtained as a white solid (401 mg, quantitative yield) and used as is without purification. 1 H NMR (400MHz, DMSO) δ8.02(s, 4H), 7.51-7.10(m, 1H), 3.44(t, J=9.0Hz, 4H), 3.36(s, 4H), 2.80(m, 4H), 1.59(s, 6H). TLC-MS, [M+H] + =243

[0119] (e) Bis-acid intermediate (vi) A suspension of 3,3'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(propan-1-amine) dihydrochloride (350 mg, 1.00 Eq, 1.11 mmol) and TEA (0.51 mL, 3.30 Eq, 3.66 mmol) is cooled to 0° C. Then maleic anhydride (359 mg, 3.30 Eq, 3.66 mmol) is added. The mixture is allowed to warm to room temperature for 16 h. Then water is added and the mixture is acidified to pH=2 with 2M HCl solution. The aqueous phase is extracted with ethyl acetate (6×). The combined organic phases are dried over sodium sulfate, filtered and concentrated to dryness. The crude material was obtained as a colorless oil (360 mg, 74%) and was used directly without purification. 1 H NMR (400MHz, DMSO) δ9.06(s, 2H), 6.45-6.33(m, 2H), 6.23(d, J=12.5Hz, 2H), 3.41(t, J=6 .2Hz, 4H), 3.35(s, 4H), 3.22(td, J=7.0, 5.6Hz, 4H), 1.69(t, J=6.6Hz, 4H), 1.58(s, 6H). LC-MS(ESI+), [M+H] + =439, [MH] -=437

[0120] (f) SPC-TB-0001 To a solution of (2Z,2'Z)-4,4'-((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(propane-3,1-diyl))bis(azanediyl))bis(4-oxobut-2-enoic acid) (360 mg, 1.00 Eq, 821 μmol) in acetone (5.5 mL) was added sodium acetate (54.0 mg, 0.80 Eq, 657 μmol). The mixture was refluxed under normal atmosphere for 16 h. The reaction mixture was then cooled to room temperature and diluted with EtOAc. The organic phase was washed with saturated NaHCO3 solution (1x), dried over sodium sulfate, filtered and concentrated to dryness to give a dark brown oil. The crude material was purified by column chromatography (silica gel, EtOAc in cyclohexane, gradient 0-60% EtOAc) to give the desired product as a yellowish oil which solidified (37 mg, 11%). 1 H NMR (400MHz, DMSO) δ7.00(s, 4H), 3.46(t, J=6.9Hz, 4H), 3.35(t, J=6.0Hz, 4H), 3.28(s, 4H), 1.74 -1.66(m, 4H), 1.53(s, 6H). TLC-MS, [M+H] + =403

[0121] (g) Bis-amine intermediates (vii) 3,3'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))dipropanenitrile was prepared according to steps (a) and (b) of scheme method 1. To a suspension of 3,3'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))dipropanenitrile (10.3 g, 1.00 Eq, 44.0 mmol) in THF (393 mL) was slowly added 1-M BH3·THF solution in THF (220 mL, 5.00 Eq, 220 mmol) at 37 °C under nitrogen. The solution was stirred at 0 °C for 1 h and at reflux for 1 h. The reaction mixture was cooled to 0° C. and MeOH (1.26 mL) was added dropwise followed by 37%-HCl (1.5.8 mL, 1.00 Eq, 44.0 mmol). The reaction mixture was then warmed to room temperature. The solvent was removed under reduced pressure (200 mbar, 40° C.). The residue was basified with 2M NaOH and extracted with EtOAc (3×). The combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was obtained directly without purification (11.5 g, quant.). TLC-MS, [M+H] + =243

[0122] (h)SPC-TB-0001 3,3'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(propan-1-amine) (840 mg, 1.00 Eq, 3.47 mmol) was suspended in saturated sodium bicarbonate solution (26.7 mL). The mixture was cooled to 0° C. and then methyl 2,5-dioxo-2,5-dihydro-1H-pyrrole-1-carboxylate (v-2) (1.08 g, 2.00 Eq, 6.93 mmol) was added. The yellow suspension was stirred at 0° C. for 2 h. The aqueous phase was extracted with DCM (3×). The combined organic phases were washed with brine (1×) and concentrated. The crude material was purified by column chromatography (silica gel, EtOAc in cyclohexane, EtOAc up to 100%) to give the title compound (294 mg, 21%) as a white solid. 1H NMR (400 MHz, DMSO) δ 7.00 (s, 4H), 3.46 (t, J = 6.9 Hz, 4H), 3.35 (t, J = 6.0 Hz, 4H), 3.28 (s, 4H), 1.74-1.66 (m, 4H), 1.53 (s, 6H). NMR was consistent with the spectrum from Method 1. TLC-MS, [M+H] + =403

[0123] Example 3: Synthesis of Compound 2 (SPC-TB-0002) Scheme Method 2

[0124] [ka]

[0125] (a) Synthesis of bicyclo[1.1.1]pentane-1,3-diyldimethanol (ii) To a solution of dimethylbicyclo[1.1.1]pentane-1,3-dicarboxylate (25.38 g, 1 eq., 137.8 mmol) in anhydrous THF (551 ml) at 0° C. under nitrogen, a 2 M solution of LiAlH4 in THF (151.6 mL, 2.2 eq., 303.1 mmol) was added dropwise. The temperature in the flask was kept below 10° C. during the addition. The reaction mixture was stirred at room temperature for 16 h. After completion of the reaction, a Fieser workup was performed to obtain the desired product bicyclo[1.1.1]pentane-1,3-diyldimethanol (19.08 g, 148.9 mmol, quant.) as a clear oil, which solidified on standing. 1 H NMR (400 MHz, DMSO) δ 4.39 (t, J = 5.6 Hz, 2H), 3.35 (d, J = 5.6 Hz, 4H), 1.45 (s, 6H). TLC (60% EtOAc / cyclohexane). RF product 0.2. KMNO4 stain.

[0126] (b) Synthesis of di-tert-butyl 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))diacetate (iii) To bicyclo[1.1.1]pentane-1,3-diyldimethanol (500 mg, 1 eq., 3.90 mmol) and tetrabutylammonium bromide (717 mg, 0.57 eq., 2.22 mmol) in 50% aqueous NaOH (24 mL) and toluene (12 mL) in a 2:1 ratio was added tert-butyl 2-bromoacetate (6.09 g, 4.64 mL, 8 eq., 31.2 mmol). The reaction mixture was stirred vigorously at room temperature for 16 h. After completion of the reaction, water and EtOAc were added and the layers were separated. The aqueous layer was extracted with EtOAc (3x). The combined organic layers were then washed with brine, dried over anhydrous MgSO4, and concentrated under vacuum. The residue was chromatographed (0% to 40% EtOAc / cyclohexane) to give the desired product, di-tert-butyl 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))diacetate (900 mg, 2.52 mmol, 64.7%) as a white solid. 1 H NMR (400 MHz, CDCl3) δ 3.96 (s, 4H), 3.53 (s, 4H), 1.73 (s, 6H), 1.47 (s, 18H). TLC (20% EtOAc / cyclohexane). RF product 0.5. CAM / p-anisaldehyde stain. TLC-MS: [M+H] + = 244 (excluding the two t-Bu groups).

[0127] (c) Synthesis of 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-ol) (iv) To a solution of di-tert-butyl 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))diacetate (860 mg, 1 eq., 2.41 mmol) in anhydrous THF (12.1 mL) at 0 °C under nitrogen, a 2 M solution of LiAlH4 in THF (201 mg, 2.65 mL, 2.00 mol, 2.2 eq., 5.31 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 2 h. After completion of the reaction, a Fieser workup was performed to give the desired product 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-ol) (420 mg, 1.94 mmol, 80.5%) as a clear oil. 1 H NMR (400 MHz, DMSO) δ 4.54 (t, J = 5.4 Hz, 2H), 3.47 (tdd, J = 6.1, 5.2, 1.1 Hz, 4H), 3.40-3.36 (m, 8H), 1.58 (s, 6H). TLC (50% EtOAc / cyclohexane). RF product 0.1. CAM / p-anisaldehyde stain. No UV activity.

[0128] (d) Synthesis of 1,1'-(((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(1H-pyrrole-2,5-dione)-(SPC-TB-0002) To a solution of triphenylphosphine (273 mg, 2.25 eq., 1.04 mmol) in anhydrous THF (2.89 mL) in a microwave vial tube cooled to 0° C. under nitrogen, DIAD (210 mg, 202 μL, 2.25 eq., 1.04 mmol) was slowly added dropwise over 5 min. The yellow reaction mixture was stirred at 0° C. for 5 min. Then, 2,2′((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-ol) (100 mg, 1 eq., 462 μmol) in THF (2.89 mL) was added and stirred again at 0° C. for 5 min. Finally, maleimide (108 mg, 2.40 eq., 1.11 mmol) was added and the resulting reaction mixture was allowed to warm to room temperature after 5 min and stirred at ambient temperature for 16 h. After completion of the reaction, the reaction mixture was concentrated and the residue was chromatographed (0% to 80% EtOAc / cyclohexane) to give the desired product 1,1'-(((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(1H-pyrrole-2,5-dione) (80.0 mg, 214 μmol, 46.2%) as a white solid. 1 H NMR (400 MHz, DMSO) δ 7.03 (s, 4H), 3.61-3.49 (m, 4H), 3.51-3.42 (m, 4H), 3.31 (s, 4H), 1.44 (s, 6H). TLC (80% EtOAc / cyclohexane). RF product 0.75. KMNO4 stain. Slightly UV active. TLC-MS: [M+H] + =375.

[0129] (e) Synthesis of 2,2'-(((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) (v) To a solution of triphenylphosphine (225 mg, 3.25 eq., 857 μmol) in anhydrous THF (1.65 mL) in a microwave vial tube cooled to 0° C. under nitrogen, DIAD (173 mg, 167 μL, 3.25 eq., 857 μmol) was slowly added dropwise over 5 min. The yellow reaction mixture was stirred at 0° C. for 5 min. Then, 2,2′-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-ol) (57.0 mg, 1 eq., 264 μmol) in THF (1.65 mL) was added and stirred again at 0° C. for 5 min. Finally, isoindoline-1,3-dione (132 mg, 3.40 eq., 896 μmol) was added and the resulting reaction mixture was allowed to warm to room temperature after 5 min and stirred at ambient temperature for 48 h. After completion of the reaction, the reaction mixture was concentrated and the residue was chromatographed (0% to 40% EtOAc / cyclohexane) to give the desired product, 2,2'-(((bicyclo[1.1,1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) (108 mg, 228 μmol, 86.4%) as a clear oil, which solidified to a white solid on standing. 1 H NMR (400 MHz, CDCl3) δ 7.89-7.80 (m, 4H), 7.76-7.66 (m, 4H), 3.86 (t, J = 5.9 Hz, 4H), 3.65 (t, J = 5.9 Hz, 4H), 3.40 (s, 4H), 1.52 (s, 6H). TLC (30% EtOAc / cyclohexane). RF product 0.25. CAM stain. UV active. TLC-MS: [M+H] + =475.

[0130] (f) Synthesis of 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-amine) (vi) To a solution of 2,2'-(((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(isoindoline-1,3-dione) (108 mg, 1 eq., 228 μmol) in ethanol (7.59 mL) was added hydrazine hydrate (45.6 mg, 44.3 μL, 4 eq., 910 μmol). The reaction mixture was heated to 50° C. and stirred for 16 h. Note: A white precipitate precipitates after 1 h. After completion of the reaction, the white solid is removed by filtration and the filtrate is concentrated to give the desired product 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-amine) (95 mg, 0.44 mmol, quant.) as a white solid. The crude product is used in the next step without further purification. 1 H NMR (400 MHz, DMSO) δ 3.36 (s, 4H), 3.33 (t, J=5.9 Hz, 4H), 2.62 (t, J=5.9 Hz, 4H), 1.59 (s, 4H). No amine protons observed. TLC (10% MeOH / DCM). RF product baseline. Ninhydrin stain. No UV activity.

[0131] (g) Synthesis of 1,1'-(((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(1H-pyrrole-2,5-dione) (SPC-TB-0002) To a solution of 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-amine) (95.0 mg, 1 eq., 443 μmol) in acetic acid (2.46 mL) was added furan-2,5-dione (21.7 mg, 5 eq., 2.22 mmol) and the reaction mixture was refluxed at 125 °C for 4 h with stirring. After completion of the reaction, acetic acid was evaporated with toluene or concentrated. The residue was chromatographed (0% to 80% EtOAc / cyclohexane) to give 1,1'-(((bicyclo[1.1,1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(1H-pyrrole-2,5-dione) (29 mg, 77 μmol, 17%) as a white solid. 1 H NMR (400 MHz, DMSO) δ 7.03 (s, 4H), 3.59-3.51 (m, 4H), 3.47 (dd, J=5.9, 4.7 Hz, 4H), 3.31 (s, 4H), 1.44 (s, 6H). TLC (80% EtOAc / cyclohexane). RF product 0.75. KMNO4 stain. Slightly UV active. TLC-MS: [M+H] + =375.

[0132] Example 4: Synthesis of Compound 3 (SPC-TB-0003)

[0133] [ka]

[0134] (a) Bis-alcohol intermediate (ii) A solution of 2M LiAlH4 in THF (55 mL, 2.50 Eq, 0.11 mol) was cooled to 0° C. under nitrogen. A solution of dimethylbicyclo[2.2.2]octane-1,4-dicarboxylate (10 g, 1.00 Eq, 44 mmol) in THF (100 mL) was then added dropwise over 1 h. The temperature in the flask was maintained below 10° C. during the addition. After the addition was complete, the solution was stirred at 0° C. for 30 min. The reaction was then quenched by performing a Fieser workup. The crude material was isolated as a colorless oil, which solidified overnight (7.4 g, 98%) and was used directly without purification. 1 H NMR (400MHz, DMSO) δ4.24 (t, J=5.5Hz, 2H), 3.01 (d, J=5.5Hz, 4H), 1.29 (s, 12H).

[0135] (b) Bis-cyano intermediate (iii) To a solution of bicyclo[2.2.2]octane-1,4-diyldimethanol (1.0 g, 1.00 Eq, 6.00 mmol) in 0.5-M NaOH (6 mL) and 1,4-dioxane (6 mL) was added acrylonitrile (1.40 mL, 6.00 Eq, 36.0 mmol). The solution was stirred at room temperature for 22 h and at 50 °C for 2 h. After cooling to room temperature, DCM (30 mL) was added to the mixture and the phases were separated. The organic phase was washed with brine (2 x 20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, EtOAc in cyclohexane, gradient 0-40% EtOAc) to give the desired product as a colorless oil that solidified (560 mg, 30%). 1 H NMR (400MHz, CDCl3) δ3.60(t, J=6.4Hz, 4H), 3.09(s, 4H), 2.57(t, J=6.4Hz, 4H), 1.42(s, 12H). TLC-MS:[M+H] + =277

[0136] (c) Bis-Boc-protected amine intermediate (iv) To a solution of 3,3'-((bicyclo[2.2.2]octane-1,4-diylbis(methylene))bis(oxy))dipropanenitrile (560 mg, 1.00 Eq, 2.03 mmol) and nickel(II) chloride-hexahydrate (626 mg, 1.3 Eq, 2.63 mmol) in MeOH (40.5 mL) at 0 °C was added NaBH4 (613 mg, 8.00 Eq, 16.2 mmol) in small portions. The black mixture was stirred for 2 h at 0 °C, after which Boc anhydride (1.33 g, 3.00 Eq, 6.08 mmol) was added and allowed to warm to room temperature overnight for 22 h. The reaction was quenched with brine (5 mL) at 0 °C and the methanol was removed under reduced pressure. Brine (500 mL) was added and the aqueous phase was extracted with diethyl ether (3 x 150 mL). The combined organic phases were washed with brine (100 mL), dried over sodium sulfate, filtered and concentrated to dryness to give the crude material (954 mg, 97%) as a yellowish oil which was used without further purification. 1 H NMR (400MHz, DMSO) δ6.69 (m, 4H), 2.96 (m, 8H), 1.57 (t, J=6.58Hz, 4H), 1.42 (m, 34H). TLC-MS, [M+H] + = 485, [M+H-Boc] = 385

[0137] (d) Bis-amine-hydrochloride precursor (v) Di-tert-butyl (((bicyclo[2.2.2]octane-1,4-diylbis(methylene))bis(oxy))bis(propane-3,1-diyl))dicarbamate (950 mg, 1.00 Eq, 1.96 mmol) was dissolved in HCl (4-M) in dioxane (4.90 mL, 10.0 Eq, 19.6 mmol) and stirred at room temperature for 14 h. The reaction mixture was concentrated under reduced pressure. The residue was triturated with diethyl ether (1×5 mL) and dried under reduced pressure. The crude product (780 mg, quantitative yield) was obtained as a yellowish solid. 1H NMR (400MHz, DMSO) δ7.90(s, 5H), 7.39-7.02(m, 1H), 3.39(t, J=6.0Hz, 4H), 2.99(s, 4H), 2.80(m, 4H), 1.79-1.71(m, 4H), 1.35(s, 12H).

[0138] (e) Bis-acid intermediate (vi) A suspension of 3,3'-((bicyclo[2.2.2]octane-1,4-diylbis(methylene))bis(oxy))bis(propan-1-amine) dihydrochloride (730 mg, 1.00 Eq, 2.04 mmol) and TEA (584 μL, 2.05 Eq, 4.19 mmol) in chloroform (21 mL) is cooled to 0 °C. Then maleic anhydride (401 mg, 2.00 Eq, 4.09 mmol) is added. The mixture is allowed to warm to room temperature for 22 h. The next morning water is added and the reaction mixture is acidified with 2-M HCl until pH = 2. The aqueous phase is extracted with ethyl acetate (3x). The combined organic phases were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material (755 mg, 77%) was obtained as a colorless oil, which was used directly without purification. 1 H NMR (400MHz, DMSO) δ9.13(s, 2H), 6.37(d, J=12.5Hz, 2H), 6.23(d, J=12.5Hz, 2H), 3.21(m, 4H), 2.97(s, 4H), 1.69(m, 4H), 1.34(m, 16H). LC-MS(ESI+), [M+H] + =481, [MH] - =479

[0139] (f) SPC-TB-0003 To a solution of (2Z,2'Z)-4,4'-((((bicyclo[2.2.2]octane-1,4-diylbis(methylene))bis(oxy))bis(propane-3,1-diyl))bis(azanediyl))bis(4-oxobut-2-enoic acid) (755 mg, 1.00 Eq, 1.57 mmol) in acetone (10.5 mL) was added acetic anhydride (890 μL, 6.00 Eq, 9.43 mmol) and sodium acetate (103 mg, 0.80 Eq, 1.26 mmol). The mixture was refluxed for 16 h. After it was cooled to room temperature, it was diluted with EtOAc and washed with saturated NaHCO3 solution. The organic phase was dried over sodium sulfate, filtered and concentrated to dryness. The crude material was purified by column chromatography (silica gel, EtOAc in cyclohexane, gradient 0-60% EtOAc) to afford the title compound (62 mg, 9%) as a colorless solid. 1 H NMR (400MHz, DMSO) δ7.00(s, 4H), 3.45(t, J=6.9Hz, 4H), 3.29(t, J=6.0Hz, 4H), 2.93(s, 4H), 1.75-1.64(m, 4H), 1.32(s, 12H). TLC-MS, [M+H] + =445

[0140] (g) Bis-amino intermediate (vii) To a solution of 3,3'-((bicyclo[2.2.2]octane-1,4-diylbis(methylene))bis(oxy))dipropanenitrile (7.59 g, 1.00 Eq, 27.5 mmol) in THF (245 mL) at 0 °C under nitrogen, a 1 M solution of BH3·THF complex in THF (1.37 mL, 5.00 Eq, 1.37 mmol) was slowly added. The reaction was stirred at 0 °C for 1 h and then refluxed for 1 h. It was cooled again to 0 °C before adding MeOH (78.7 mL) followed by concentrated hydrochloric acid (9.84 mL) and warming to room temperature for 1 h. The solvent was removed under reduced pressure (300 mbar, 40 °C) and the residue was basified with 2 M NaOH and extracted with EtOAc (4x). The combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give a colorless oil (8.3 g). The crude oil (not clean) was used without further purification.

[0141] (h)SPC-TB-0003 3,3'-((bicyclo[2.2.2]octane-1,4-diylbis(methylene))bis(oxy))bis(propan-1-amine) (500 mg, 1.00 Eq, 1.76 mmol) was suspended in sodium carbonate solution (13.5 mL). The mixture was cooled to 0° C. and then methyl 2,5-dioxo-2,5-dihydro-1H-pyrrole-1-carboxylate (545 mg, 2.00 Eq, 3.52 mmol) was added. Precipitation occurred and stirring was stopped. Stirring was aided by addition of 1,4-dioxane (5 mL). After 14 h at room temperature (no stirring), water was added and the aqueous phase was extracted with DCM (3×). The combined organic phases were washed with brine and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel, EtOAc in cyclohexane up to 100% EtOAc) to afford the title compound (170 mg, 22%) as a white solid. 1 H NMR (400MHz, DMSO) δ7.00(s, 4H), 3.45(t, J=6.9Hz, 4H), 3.29(t, J=6.0Hz, 4H), 2.93(s, 4H), 1.75-1.64(m, 4H), 1.32(s, 12H). TLC-MS, [M+H] +=445.

[0142] Example 5: Synthesis of Compound 5 (SPC-TB-0007)

[0143] [ka]

[0144] (a) Diol (ii) To a solution of dimethylbicyclo[1.1.1]pentane-1,3-dicarboxylate (25.38 g, 1 eq., 137.8 mmol) in anhydrous THF (551 ml) at 0° C. under nitrogen, a 2 M solution of LiAlH4 in THF (151.6 mL, 2.2 eq., 303.1 mmol) was added dropwise. The temperature in the flask was kept below 10° C. during the addition. The reaction mixture was stirred at room temperature for 16 h. After completion of the reaction, a Fieser workup was performed to obtain the desired product bicyclo[1.1.1]pentane-1,3-diyldimethanol (19.08 g, 148.9 mmol, quant.) as a clear oil, which solidified on standing.

[0145] The reaction was also carried out on a 50 g scale with mechanical stirring to produce 31.5 g of the desired product (91% yield). 1 H NMR (400MHz, DMSO) δ4.39(t, J=5.6Hz, 2H), 3.35(d, J=5.6Hz, 4H), 1.45(s, 6H).

[0146] (b) Diesters (iii) To a solution of bicyclo[1.1.1]pentane-1,3-diyldimethanol (500 mg, 1 eq., 3.90 mmol), tetrabutylammonium bromide (71.7 mg, 0.57 eq., 2.22 mmol), and tert-butyl 2-bromoacetate (6.09 g, 4.64 mL, 8 eq., 31.2 mmol) in toluene (1.2 mL) was added NaOH (33 w% in water, 24 mL). The reaction mixture was stirred vigorously at room temperature for 16 h (color turns yellow). After completion of the reaction, the phases were separated and the toluene layer was collected. The aqueous layer was extracted with DCM (3x). The combined organic layers were then washed with brine, dried over anhydrous MgSO4, and concentrated under vacuum. The residue was purified on silica (0% to 40% EtOAc in cyclohexane) to give di-tert-butyl 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))diacetate (900 mg, 2.52 mmol, 64.7%) as a white solid. 1 H NMR (400MHz, CDCl3) δ3.96(s, 4H), 3.53(s, 4H), 1.73(s, 6H), 1.47(s, 18H).

[0147] (c) Diol (iv) To a solution of di-tert-butyl 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))diacetate (860 mg, 1 eq., 2.41 mmol) in anhydrous THF (12.1 mL) at 0 °C under nitrogen, a 2 M solution of LiAlH4 in THF (201 mg, 2.65 mL, 2.00 mol, 2.2 eq., 5.31 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 5 h. After completion of the reaction, a Fieser workup was performed to give the desired product 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-ol) (420 mg, 1.94 mmol, 80.5%) as a clear oil. 1H NMR (400MHz, DMSO) δ4.54(t, J=5.4Hz, 2H), 3.47(tdd, J=6.1, 5.2, 1.1Hz, 4H), 3.40-3.36(m, 8H), 1.58(s, 6H).

[0148] (d) Diester (v) To a solution of 2,2'-((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethan-1-ol) (3.40 g, 1 eq., 1.5.7 mmol), tetrabutylammonium bromide (2.89 g, 0.57 eq., 8.96 mmol) in toluene (48 mL) was added NaOH (33 w% in water, 97 mL). The reaction mixture was vigorously stirred at room temperature for 16 h. After completion of the reaction (TLC), the phases were separated and the toluene layer was collected. The reaction mixture was vigorously stirred at room temperature for 16 h (color turns yellow). After completion of the reaction, the phases were separated and the toluene layer was collected. The aqueous layer was extracted with DCM (3x). The combined organic layers were then washed with brine, dried over anhydrous MgSO4 and concentrated under vacuum. The residue was chromatographed (0% to 40% EtOAc / cyclohexane) to give the desired product, di-tert-butyl 2,2'-((((bicyclo[1.1,1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy)) diacetate (4.91 g, 11.0 mmol, 70.3%) as a clear oil. 1 H NMR (400MHz, CDCl3) δ4.03(s, 4H), 3.73-3.61(m, 8H), 3.48(s, 4H), 1.68(s, 6H), 1.48(s, 18H).

[0149] (e) Diol (vi) To a solution of di-tert-butyl 2,2'-((((bicyclo[1.1,1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))diacetate (4.91 g, 1 eq., 11.0 mmol) in anhydrous THF (73.6 mL) at 0°C under nitrogen was added dropwise a 1 M solution of LiAlH4 in THF (1.05 g, 27.6 mL, 1.00 mol, 2.5 Eq, 27.6 mmol). The reaction mixture was stirred at room temperature for 5 h. After completion of the reaction, a Fieser workup was performed to give the desired product 2,2'-((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethan-1-ol) (3.3 g, 11 mmol, 98%) as a clear oil. 1 H NMR (400MHz, DMSO) δ4.55 (t, J=5.5Hz, 2H), 3.54-3.35 (m, 20H), 1.58 (s, 6H).

[0150] (f) Di-mesylate (vii) 2,2'-((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethan-1-ol) (200 mg, 1 Eq, 657 μmol) was dissolved in DCM (3.29 mL) before TEA (332 mg, 458 μL, 5.00 Eq, 3.29 mmol) was added and the mixture was cooled to 0° C. After cooling, methanesulfonyl chloride (301 mg, 203 μL, 4.00 Eq, 2.63 mmol) was added and the mixture was maintained at 0° C. for 15 min before being allowed to warm to room temperature. After 2 h the reaction was judged complete, diluted with DCM and quenched with water. The layers were separated and the aqueous layer was extracted with DCM (3×). The combined organic layers were washed with brine, dried (Na2SO4) and concentrated under reduced pressure to give ((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl) dimethanesulfonate as a clear oil (yield assumed to be quantitative) which was taken directly to the next step without further purification. 1 H NMR (400MHz, CDCl3) δ4.42-4.34(m, 4H), 3.80-3.75(m, 4H), 3.68-3.57(m, 8H), 3.45(s, 4H), 3.07(s, 6H), 1.66(s, 6H).

[0151] (g) Substitution product (viii) (((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl) dimethanesulfonate (454 mg, 1 Eq, 0.986 mmol) was dissolved in MeCN (2 mL) followed by addition of KI (32.7 mg, 0.2 Eq, 197 μmol), K2CO3 (545 mg, 4 Eq, 3.94 mmol), and 3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione (prepared according to Eur. J. Org. Chem, 2012, 31, 6165. without deviation from the protocol to produce only the exo isomer) (489 mg, 3 Eq, 2.96 mmol). The mixture was heated to 70° C. for 18 h. The reaction showed a 1:1 mixture of mono- and di-substituted by LC-MS and an additional equivalent of 3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione and K2CO3 was added. After 6 h, the reaction was cooled to room temperature and concentrated under reduced pressure. The residue was taken up in a 1:1 mixture of EtOAc / H2O and the aqueous solution was extracted with EtOAc (5×). The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure. The crude residue was purified on silica (80-100% EtOAc in cyclohexane) to give 2,2'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione) (248 mg, 414 μmol, 42.0%) and a colorless oil. 1 H NMR (400MHz, DMSO) δ6.55(t, J=0.9Hz, 4H), 5.12(t, J=0.9Hz, 4H), 3.52-3.42(m, 16H), 3.35(s, 4H), 2.93(s, 4H), 1.56(s, 6H).

[0152] (h) Substitution product (viii) Triphenylphosphine (194 mg, 2.25 Eq, 739 μmol) was dissolved in THF (2.05 mL) and then cooled to 0° C. DIAD (149 mg, 144 μL, 2.25 Eq, 739 μmol) was added slowly over 2-3 min. The yellow reaction mixture was stirred at 0° C. for 5 min. Then, 2,2'-((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethan-1-ol) (100 mg, 1 Eq, 329 μmol) was added as a solution in THF (2.05 mL) over 1 min and stirred at 0° C. for 5 min. Finally, 3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione (130 mg, 2.40 Eq, 788 μmol) was added as a solid to the reaction mixture. The resulting suspension was left at 0° C. for 5 min, during which time most of the maleimide had dissolved. The cooling bath was then removed and the reaction was stirred at ambient temperature overnight. The reaction was concentrated in vacuo and purified on silica (80-100% EtOAc in cyclohexane followed by 0-20% MeOH in DCM) to give 2,2'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione) (0.12 g, 0.21 mmol, 63%, +4 w% PPhO) as an oil. 1 H NMR (400MHz, DMSO) δ6.55(d, J=1.0Hz, 4H), 5.12(d, J=1.0Hz, 4H), 3.55-3.41(m, 16H), 3.35(s, 4H), 2.93(s, 4H), 1.56(s, 6H).

[0153] (k)SPC-TB-0007 2,2'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione) (248 mg, 1 Eq, 414 μmol) was dissolved in toluene (18 mL) and heated to reflux overnight (bath temperature set at 120° C. and reflux condenser open to atmosphere). TLC showed complete consumption of SM and the reaction was concentrated under reduced pressure. The crude product was purified on silica (50-80% EtOAc in cyclohexane) to give 1,1'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(1H-pyrrole-2,5-dione) (89 mg, 0.19 mmol, 46%) as a colorless oil that solidified on standing. 1 H NMR (400MHz, DMSO) δ7.02(s, 4H), 3.60-3.40(m, 16H), 3.33(s, 4H), 1.53(s, 6H). TLC-MS(APCI):[M+H] + =463.4.

[0154] (k)vi) from SPC-TB-0007 PPh3 (2.90 g, 2.25 Eq, 11.09 mmol) was dissolved in THF (30.8 mL) and then cooled to 0 °C. DIAD (2.24 g, 2.16 mL, 2.25 Eq, 11.09 mmol) was added slowly over 5 min. The yellow reaction mixture was stirred at 0 °C for 10 min. Then 2,2'-((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethan-1-ol) (1.50 g, 1 Eq, 4.93 mmol) was added dropwise as a solution in THF (30.8 mL) and stirred at 0 °C for an additional 5 min. After this time, the protected maleimide (endo / exo mixture) (1.95 g, 2.40 Eq, 11.83 mmol) was added as a solid to the reaction mixture. The resulting suspension was left at 0° C. for 5 min during which time most of the maleimide dissolved. The cooling bath was then removed and the reaction was stirred at ambient temperature overnight. The reaction was concentrated under reduced pressure and the crude residue was dissolved in ethanol (14.93 mL) and warmed to 30° C. to give a clear solution. A solution of ZnCl2 (2.85 g, 2 Eq, 20.9 mmol) in EtOH (14.93 mL) at 30° C. was added with vigorous stirring and left at room temperature overnight (with stirring) to form a white precipitate. The precipitate was filtered and washed with EtOH. After concentration under reduced pressure, the crude brown oil was purified on silica (80–100% EtOAc in cyclohexane) to give a mixture of endo-endo, endo-exo, exo-exo, and the deprotected product (2.64 g, exact distribution of products undetermined).

[0155] The yellow oil was dissolved in toluene (1.93 mL) and heated to reflux overnight (bath temperature set at 120 °C and reflux condenser open to atmosphere). The reaction was concentrated under reduced pressure and the crude product was purified on silica (50-80% EtOAc in cyclohexane) to afford 1,1'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(1H-pyrrole-2,5-dione) (1.086 g, 2.348 mmol, 47.65%) as a clear oil that solidified on standing.

[0156] Example 6: Synthesis of Compound 6 (SPC-TB-0013)

[0157] [ka]

[0158] (a) Diester (ii) To a solution of 2,2'-((((bicyclo[1.1.1]pentane-1,3-diylbis(methyl-5-yl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethan-1-ol) (3.0 g, 1.0 eq., 9.9 mmol), tetrabutylammonium bromide (1.80 g, 0.57 eq., 5.60 mmol), and tert-butyl 2-bromoacetate (15.0 g, 12.0 mL, 8 eq., 79.0 mmol) in toluene (30 mL) was added NaOH (33 w% in water, 61 mL). The reaction mixture was vigorously stirred at room temperature for 16 h. After completion of the reaction (TLC), the phases were separated and the toluene layer was collected. The aqueous layer was extracted with DCM (3x). The combined organic layers were then washed with brine, dried over anhydrous MgSO4, and concentrated under vacuum. The residue was chromatographed (30% to 60% EtOAc / cyclohexane) to give the desired product, di-tert-butyl 2,2'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy)) diacetate (2.35 g, 4.41 mmol, 45.0%) as a yellowish oil. 1 H NMR (400MHz, CDCl3) 4.02(s, 4H), 3.70(m, 8H), 3.62(m, 8H), 3.47(s, 4H), 1.67(s, 6H), 1.47(s, 18H). TLC-MS(APCI):[M+H] + = 420.7 (excluding the two t-Bu groups).

[0159] (b) Diol (iii) To a solution of di-tert-butyl 2,2'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))diacetate (2.15 g, 1 eq., 4.04 mmol) in anhydrous THF (40.4 mL) at 0° C. under nitrogen was added dropwise a solution of LiAlH4 in THF (4.44 mL, 2.00 mol, 2.2 Eq, 8.88 mmol). The reaction mixture was allowed to warm overnight for 17 h. After completion of the reaction, a Fieser workup was performed to give the desired product 2,2'-((((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethan-1-ol) (1.46 g, 4.04 mmol, 92%) as a clear oil. 1 H NMR (400MHz, CDCl3) 3.73 (m, 4H), 3.64 (m, 20H), 3.47 (s, 4H), 1.68 (s, 6H).

[0160] (c) Substitution product (iv) A microwave vial was charged with triphenylphosphine (1.50 mg, 2.25 Eq, 573 μmol) and THF (1.59 ml) was added. The resulting clear solution was cooled to 0°C. DIAD (116 mg, 111 μL, 2.25 Eq, 573 μmol) was added slowly over 2-3 min. The yellow reaction mixture was stirred at 0°C for 5 min. Then, 2,2'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethan-1-ol) (100 mg, 1 Eq, 255 μmol) was added over 1 min and stirred for 5 min. Finally, 3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione (101 mg, 2.40 Eq, 611 μmol) was added as a solid to the reaction mixture. The resulting suspension was left at 0° C. for 5 min during which time most of the maleimide had dissolved. The cooling bath was then removed and the reaction was stirred at ambient temperature overnight (18 h). The reaction mixture was then concentrated under vacuum and passed through silica eluting with 15% MeOH in DCM to yield the title compound with some impurity by TLC, which was taken on to the next step without further purification. TLC-MS(APCI):[M+H] + =551.1 (excluding furan protecting group).

[0161] (d) SPC-TB-0013 2,2'-((((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione) (1.75 mg, 1.0 eq., 255 μmol) was suspended in toluene (11.1 mL) and refluxed overnight for 18 h. After complete consumption of the starting material, the reaction mixture was concentrated and the residue was purified by column chromatography (silica gel, 60-80% EtOAc in cyclohexane) to give the title compound (87 mg, 62%, yield over two steps) as a colorless oil. 1 H NMR (400MHz, DMSO): 7.02 (s, 4H), 3.46 (m, 24H), 3.32 (s, 4H), 1.57 (s, 6H). TLC-MS(APCI):[M+H] + =551.1

[0162] Example 7: Synthesis of Compound 7 (SPC-TB-0014)

[0163] [ka]

[0164] (a) Diester (ii) To a solution of 2,2'-(((((bicyclo[1.1.1]pentane-1,3-diylbis(methylene))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethane-2,1-diyl))bis(oxy))bis(ethan-1-ol) (1.46 g, 1.0 eq., 3.72 mmol), tetrabutylammonium bromide (0.68 g, 0.57 eq., 2.12 mmol), and tert-butyl 2-bromoacetate (5.80 g, 4.43 mL, 8 eq., 29.8 mmol) in toluene (11.4 mL) was added NaOH (33 w% in water, 22.9 mL) at 0°C. The reaction mixture was allowed to warm to room temperature for 17 h. After completion (TLC), the phases were separated and the toluene layer was collected. The aqueous layer was extracted with DCM (3x, difficult and time-consuming to separate). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (10% to 60% EtOAc / cyclohexane) to give the title compound di-tert-butyl 1,1'-(bicyclo[1.1,1]pentane-1,3-diyl)bis(2,5,8,11-tetraoxatridecan-1,3-oate) (1.31 g, 56.7%) as a yellow oil. 1 H NMR (400 MHz, CDCl3): 4.01 (s, 4H), 3.71 (m, 8H), 3.66 (m, 8H), 3.62 (m, 8H), 3.47 (s, 4H), 1.67 (s, 4H), 1.47 (s, 18H). TLC-MS (APCI): 508 (except for 2x t-butyl ester).

[0165] (b) Diol (iii) To a solution of di-tert-butyl 1,1'-(bicyclo[1.1,1]pentane-1,3-diyl)bis(2,5,8,11-tetraoxatridecan-1,3-oate) (1.31 g, 1 Eq, 2.11 mmol) in anhydrous THF (152 mg, 21.1 mL, 0.100 mol, 1 Eq, 2.11 mmol) under nitrogen at 0° C., a 2 M solution of LAH in THF (1.76 mg, 2.32 mL, 2.2 Eq, 4.64 mmol) was added dropwise. The temperature was kept below 10° C.

[0166] The resulting suspension was allowed to warm to room temperature. The next morning the reaction mixture was no longer stirred (diluted in half to allow stirring). TLC shows complete conversion of sm after 18 hours. After completion of the reaction, a Fieser workup was performed. The title compound was isolated as a colorless oil (1.03 g, quantitative yield). 1 H NMR (400MHz, CDCl3): 3.66 (m, 32H), 3.46 (s, 4H), 1.67 (s, 6H). TLC-MS(APCI):[M+H] + =481.1.

[0167] (c) Di-mesylate (iv) A mixture of 1,1'-(bicyclo[1.1,1]pentane-1,3-diyl)bis(2,5,8,11-tetraoxatridecan-1,3-ol) (100 mg, 1.00 Eq, 0.21 mmol) and triethylamine (116 μL, 4.00 Eq, 0.83 mmol) in DCM (1.04 mL) was cooled to 0° C. Methanesulfonyl chloride (48.3 μL, 3.00 Eq, 0.62 mmol) was added. The reaction mixture was stirred at 0° C. for 15 min and warmed to room temperature for 2 h. After completion of the reaction, it was diluted with DCM, water was added, the phases were separated and the aqueous phase was extracted with DCM (3×). The combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure. 146 mg (110%) of crude material was isolated which was used directly without purification. 1 H NMR (400MHz, CDCl3) δ3.67-3.60(m, 32H), 3.47(s, 4H), 3.08(s, 6H), 1.67(s, 6H).

[0168] (d) Substitution product (v) Bicyclo[1.1.1]pentane-1,3-diylbis(2,5,8,11-tetraoxatridecane-1,13-diyl) dimethanesulfonate (1.46 mg, 229 μmol, 1.00 Eq.) was dissolved in MeCN (4.50 mL). KI (7.61 mg, 45.9 μmol, 0.20 Eq.), K2CO3 (1.58 mg, 1.15 mmol, 5.00 Eq.), and (3aR,4R,7S,7aS)-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione (1.14 mg, 688 μmol, 3.00 Eq.) were added. The mixture was heated at 70 °C for 44 h. After cooling to room temperature, it was concentrated, retaken in DCM, filtered (washed with ether) and concentrated. TLC-MS (APCI): [M+H] + =774 (furan protected intermediate).

[0169] (e)SPC-TB-0014 The concentrated material from the previous step was suspended in toluene (5.00 mL) and heated to reflux for 5 h. TLC shows partial conversion to product. The reaction mixture was concentrated and filtered through silica gel eluting with DCM / MeOH, 0-10% MeOH. The filtrate was concentrated under vacuum and TLC-MS confirmed the presence of product. The mixture was not further purified. TLC-MS(APCI):[M+H] + =639

[0170] Example 8: Thiol Recombination General Procedure The compound to be tested (1 eq.) was dissolved in aqueous medium (0.02-0.05 M) and 4 eq. of cysteine ​​reagent (N-Fmoc-cysteine ​​(C1) or N-Cbz-cysteine ​​(C2)) was added. Two test solutions were used as aqueous medium: test solution 1 was a phosphate buffer (pH=5.4) with or without an emulsifier (e.g., Eumulgin) and test solution 2 was an aqueous solution containing 0.49% (w / w) sodium benzoate and 0.30% (w / w) citric acid with or without an emulsifier (e.g., Eumulgin).

[0171] To make phosphate buffer, a 0.1 M solution of citric acid (using citric acid monohydrate) and a 0.2 M solution of Na2HPO4 (using Na2HPO4 or Na2HPO4·2H2O) were prepared and mixed in the following ratio: 44.25 mL / 55.75 mL = mL 0.1 M citric acid / mL 0.2 M Na2HPO4 to obtain a buffer solution with pH = 5.4.

[0172] The tests were carried out at an ambient temperature of 30°C in LC-MS vials or small glass vials with stirring by a small magnetic stirrer (see photo 1). The reactions were carried out under normal atmosphere. The reactions were monitored by LC-MS. The reaction scale was 4-10 mg of the test compound. To calculate the conversion to the product, the ratios between the cysteine ​​reagent, the mono-Michael addition product (mono), and the bis-Michael addition product (bis) were compared as shown in the scheme below.

[0173] All compounds show comparable or improved reactivity with cysteine ​​derivatives compared to the reference compound.

[0174] [ka]

[0175] [Table 2]

[0176] [Table 3]

[0177] [Table 4]

[0178] [Table 5]

Claims

1. A compound of formula I or a pharma- ceutically acceptable salt thereof. 【Chemistry 1】 (Y is C 3-11 is cycloalkyl, Z is a straight or branched chain C 1-14 alkyl, where one or more CH 2 The groups are independently -(CH 2 -O-CH 2 ) -, -(CH 2 -CH 2 -O)-, -(O-CH 2 -CH 2 )-, -O-, -NH-, or -NR-, where R is a straight or branched C 1-6 It is an alkyl group.

2. Y is C 4-11 Bridged bicycloalkyl etc. 3-11 2. The compound of claim 1, or a pharma- ceutically acceptable salt thereof, which is a bicycloalkyl.

3. 2. The compound of claim 1 having formula II, or a pharma- ceutically acceptable salt thereof. 【Chemistry 2】 (Y is C 3-11 is cycloalkyl, L is CH 2 and Z is a straight or branched chain C 1-13 alkyl, where one or more CH 2 The groups are independently -(CH 2 -O-CH 2 ) -, -(CH 2 -CH 2 -O)-, -(O-CH 2 -CH 2 )-, -O-, -NH-, and -NR-, where R is a straight or branched C 1-6 It is an alkyl group.

4. Y is C 4-11 Bridged bicycloalkyl etc. 3-11 4. The compound of claim 3, or a pharma- ceutically acceptable salt thereof, which is bicycloalkyl.

5. 2. The compound of claim 1 having formula III: or a pharma- ceutically acceptable salt thereof. 【Chemistry 3】 (Y is C 4-11 is a bicycloalkyl; X is selected from O, NH, and NR, where R is a straight or branched chain C 1-6 is alkyl, Z is a straight or branched chain C 1-12 alkyl, where one or more CH 2 The groups are independently -(CH 2 -O-CH 2 ) -, -(CH 2 -CH 2 -O)-, -(O-CH 2 -CH 2 )-, -O-, -NH-, and -NR-, where R is a branched or straight chain C 1-6 It is an alkyl group.

6. 2. The compound of claim 1 having formula IV: or a pharma- ceutically acceptable salt thereof. 【Chemistry 4】 (Y is C 5-11 is a bridged bicycloalkyl; Z is a straight or branched chain C 1-11 alkyl, where one or more CH 2 The groups are independently -(CH 2 -O-CH 2 ) -, -(CH 2 -CH 2 -O)-, -(O-CH 2 -CH 2 )-, -O-, -NH-, and -NR-, where R is a branched or straight chain C 1-6 It is an alkyl group.

7. 2. The compound of claim 1 having the formula V, or a pharma- ceutically acceptable salt thereof. 【Chemistry 5】 (In the formula, Y is C 5-11 is a bridged bicycloalkyl; G is - (CH 2 -O-CH 2 ) -, -(CH 2 -CH 2 -O)-, -(O-CH 2 -CH 2 ) - and n is 1 to 4, preferably 2 or 3, and m is 0 to 8, preferably 0 to 3.

8. Y is bicyclo[1.1.1]pentane, n is 2 or 3, and m is 0, 1, 2 or 3; or Y is bicyclo[2.2.2]octane, n is 3, and m is 0; 8. The compound of claim 7 or a pharma- ceutically acceptable salt thereof.

9. 9. The compound according to any one of claims 1 to 8, wherein Y is selected from bicyclo[1.1.1]pentane, bicyclo[2.1.1]hexane, bicyclo[2.2.1]heptane, bicyclo[3.1.1]heptane, bicyclo[2.2.2]octane, bicyclo[3.2.1]octane, preferably from bicyclo[1.1.1]pentane and bicyclo[2.2.2]octane, or a pharma- ceutically acceptable salt thereof.

10. A cosmetic formulation comprising at least one compound according to any one of claims 1 to 9 or a pharma- ceutically acceptable salt thereof.

11. 11. The cosmetic formulation of claim 10, further comprising at least one cosmetic additive selected from the group consisting of surfactants, oil components, emulsifiers, pearlescent waxes, consistency improvers, thickeners, superfatting agents, stabilizers, polymers, silicone compounds, fats, waxes, lecithin, phospholipids, UV protection agents, moisturizers, biogenic agents, antioxidants, deodorants, antiperspirants, antidandruff agents, film formers, bulking agents, insect repellents, self-tanning agents, tyrosine inhibitors (bleaching agents), hydrotropes, solubilizers, preservatives, fragrance oils and dyes, and mixtures thereof.

12. 12. The cosmetic formulation of claim 10 or 11, further comprising a carrier, preferably selected from water, a C(2-6)-alcohol, a C(1-10) polyol, and an oil component.

13. Use of a compound according to any one of claims 1 to 9 for the manufacture of a cosmetic formulation, preferably a hair care product.

14. A method for the treatment of keratinous materials such as hair, comprising the step of applying a compound according to any one of claims 1 to 9 or a cosmetic preparation according to any one of claims 10 to 12 to said keratinous materials.

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