Compound having ALK inhibitory action

Abstract

Provided is a compound having an ALK inhibitory action, or a salt thereof.　The compound or salt thereof is represented by formula (1).

Description

Compounds that have ALK inhibitory activity

[0001] The present invention relates to a compound having ALK inhibitory activity, and a pharmaceutical product containing the same.

[0002] Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase belonging to the insulin receptor family, and it has been reported that ALK gene abnormalities (translocations, point mutations, and gene amplification) are involved in carcinogenesis. For example, in lung cancer, ALK binds to the intracellular skeletal protein EML4 through chromosomal translocation, generating EML4-ALK, which has active tyrosine kinase activity and thus acquires carcinogenic potential (Non-Patent Literature 1). Following these discoveries, the development of compounds with ALK inhibitory activity is progressing (Non-Patent Literature 2, Non-Patent Literature 3).

[0003] Nature, Vol. 448, pp. 561–566, 2007; Cancer Cell, Vol. 19, pp. 679–690, 2011; Nature Cancer, Vol. 4, pp. 330–343, 2023.

[0004] The object of the present invention is to provide novel compounds having ALK inhibitory activity. Furthermore, it is to provide pharmaceuticals containing these compounds as active ingredients that are useful for the treatment and prevention of cancer.

[0005] The inventors of this invention conducted intensive research to solve the above problems and discovered that the compound represented by the following formula (1) has ALK inhibitory activity. Furthermore, they discovered that the compound represented by the following formula (1) has proliferation inhibitory activity against ALK fusion gene-positive cancer cells.

[0006] In other words, in one aspect of the present invention, the following invention is provided: [1] A compound represented by the following formula (1) or a salt thereof: In the formula, R １ (a1) R １ C １ ~C ６ Alkyl, or C ２ ~C ７ It is an alkenil; (a2)R １ and P１ , R １ and the carbon atom to which P １ is bonded together with the nitrogen atom to which P is bonded form a 4- to 7-membered monocyclic saturated heterocyclic ring, and the 4- to 7-membered monocyclic saturated heterocyclic ring may be substituted with halogen, C １ -C ６ alkyl, C ２ -C ７ alkenyl, C １ -C ６ alkoxy, halo C １ -C ６ alkoxy, C １ -C ６ alkoxy C １ -C ６ alkyl and C ６ -C １４ aryl, which may be optionally substituted with one or more groups independently selected from the group consisting of, and the 4- to 7-membered monocyclic saturated heterocyclic ring may be fused with a 3- to 8-membered saturated alicyclic ring; (a3) R １ , together with R ６ , forms C ４ -C ８ alkylene, or C ４ -C ８ alkenylene; (a4) R １ and P １ , together with the carbon atom to which R １ is bonded and the nitrogen atom to which P １ is bonded form a 4- to 7-membered monocyclic saturated heterocyclic ring, and the 4- to 7-membered monocyclic saturated heterocyclic ring is further substituted with X １ , and X １ , together with R ６ , forms C ４ -C ８ alkylene, or C ４ -C ８ alkenylene; P １ is a hydrogen atom, except when R １ and P １ form a 4- to 7-membered monocyclic saturated heterocyclic ring, or C １ -C ６ alkyl, Q １ is a hydrogen atom, or C １ -C ６is alkyl, R ２ is represented by the following formula (wherein, * represents the carbon atom to which R ２ binds in formula (1), and X ２１ is either of the following (b1) or (b2): (b1) X ２１ is C １ -C ６ alkyl, C １ -C ６ alkoxy, or halo C １ -C ６ alkyl; (b2) X ２１ , X ２１ and X ２２ , together with the carbon atom they bind to, form a 3- to 8-membered saturated alicyclic ring: X ２２ , except when X ２１ and X ２２ form a 3- to 8-membered saturated alicyclic ring, is a hydrogen atom or C １ -C ６ alkyl, and X ２３ is a hydrogen atom or C １ -C ６ alkyl), and P ２ is a hydrogen atom or C １ -C ６ alkyl, and Q ２ is a hydrogen atom or C １ -C ６ alkyl, and R ３ is C １ -C ６ alkoxy C １ -C ６ alkyl, C ３ -C ８ cycloalkyl C １ -C ６ alkyl, C ３ -C ８ cycloalkoxy C １ -C ６ alkyl, C ３ -C ８ cycloalkyl C １ -C ６ alkoxy C １ -C ６ alkyl, C ３ -C８ Cycloalkylidene C １ -C ６ alkyl, C ６ -C １４ aryloxy C １ -C ６ alkyl, or C ７ -C １４ aralkyl, each of which may be substituted by one or more groups independently selected from the group consisting of halogen, C １ -C ６ alkyl, and C １ -C ６ alkoxy; P ３ is a hydrogen atom, C １ -C ６ alkyl, or C ３ -C ８ cycloalkyl C １ -C ６ alkyl, Q ３ is a hydrogen atom, or C １ -C ６ alkyl, R ４ is any one of the following (d1) to (d3), (d1) R ４ is a hydrogen atom, C １ -C ６ alkyl, or C １ -C ６ alkoxy C １ -C ６ alkyl; (d2) R ４ and P ４ form, together with the carbon atom to which R ４ is bonded and the nitrogen atom to which P ４ is bonded, a 4- to 7-membered monocyclic saturated heterocyclic ring, and said 4- to 7-membered monocyclic saturated heterocyclic ring is optionally substituted by halogen, C １ -C ６ alkyl, C ２ -C ７ alkenyl, C １ -C ６ alkoxy, halo C １ -C ６ alkyl, halo C １ -C ６ alkoxy, C １ -C ６Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups more independently selected from the group consisting of aryl groups; (d3)R ４ and Q ４ R ４ and Q ４ P forms a 3- to 8-membered saturated alicyclic ring together with the bonded carbon atoms. ４ R ４ and P ４ Unless it forms a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms or C １ ~C ６ It is alkyl, Q ４ R ４ and Q ４ Except when forming a 3- to 8-membered saturated alicyclic ring, hydrogen atoms, C １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is an alkyl group, and each of them may be substituted with one or more halogens, R ５ is aminocarbonyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl (the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ C may be substituted with a cycloalkylamino or a 3- to 10-membered monocyclic cyclic amino, or a 4- to 7-membered heterocyclyl. １ ~C ６ Alkoxy C １ ~C ６ It is alkyl, P ５ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ５ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ６ R １ Unless (a3) ​​or (a4), the following formula (In the formula, ** represents R in formula (1)) ６ X represents the carbon atom to which it is bonded. ６１ (f1)X ６１ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, or C ３ ~C ８ It is a cycloalkoxy; (f2)X ６１ is, X ６１ and X ６２ Together with the bonded carbon atoms, these atoms form a 3-8 member saturated alicyclic ring or a 4-7 member saturated heterocyclic ring, and these 3-8 member saturated alicyclic rings or 4-7 member saturated heterocyclic rings contain halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; X ６２ is, X ６１ and X ６２ Unless it forms a 3-8 member saturated alicyclic ring or a 4-7 member saturated heterocycle, a hydrogen atom or C１ ~C ６ It is alkyl; X ６３ is a hydrogen atom, or C １ ~C ６ It is represented as (alkyl), P ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ７ (h1)R ７ C １ ~C ６ It is alkyl; (h2)R ７ and P ７ R ７ The carbon atom to which it is bonded, and P ７ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered saturated heterocycle, and this 4- to 7-membered saturated heterocycle is a halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups selected more independently from the group consisting of aryl groups; P ７ R ７ and P ７ Unless it forms a 4- to 7-membered saturated heterocycle, a hydrogen atom or C １ ~C ６ It is alkyl, Q ７ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ８is either (i1) or (i2) below, and (i1) R ８ C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; (i2)R ８ and P ８ R ８ The carbon atom to which it is bonded, and P ８ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The 4- to 7-membered monocyclic saturated heterocycle may be substituted with one or more groups more independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring; P ８ R ８ and P ８ Except when forming a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms, C １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, Q８ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ９ C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, 4-7 member heterocyclyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkil, C ６ ~C １０ Aryloxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, 4-9 member heterocyclyloxy C １ ~C ６ Alkyl or 5-10 member heteroaryl C １ ~C ６ The C is alkyl, and each of them may be substituted with a halogen. ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl and 5-10 membered heteroaryl C １ ~C ６ Alkyl is C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy and Halo C１ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys, P ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, R １０ is a hydrogen atom, or C １ ~C ６ It is alkyl, P １０ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C ７ ~C １４ It is aralkyl, and each of them may be substituted with one or more halogens, Q １０ is a hydrogen atom, or C １ ~C ６ It is alkyl, R １１ C is a hydrogen atom. １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, aminocarbonyl (where the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ The aminocarbonyl is a cycloalkylamino or a 3-10 member monocyclic cyclic amino, and if the aminocarbonyl is a 3-10 member monocyclic cyclic aminocarbonyl, it may be condensed with a 3-8 member saturated alicyclic ring, or it may form a spiro ring or a crosslinking ring on the ring, and the aminocarbonyl may be a halogen, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ It may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups, P １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, L １１ It is either a single bond or -CM １１ M １２ -, - (CH ２ ) ｎ S (CH ２ ) ｍ -, - (CH ２ ) ｎ S(O)(CH ２ ) ｍ - or - (CH ２ ) ｎ S(O) ２ (CH ２ ) ｍ - where n and m are independently 1 or 2, and M １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, M １２ is a hydrogen atom, or C １ ~C ６It is alkyl. [2] Compounds represented by the following formula (2) or salts thereof: In the formula, R １ (a1) R １ C １ ~C ６ Alkyl, or C ２ ~C ７ It is an alkenil; (a2)R １ and P １ R １ The carbon atom to which it is bonded, and P １ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The 4- to 7-membered monocyclic saturated heterocycle may be substituted with one or more groups independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring; (a3) ​​R １ R ６ Together with C ４ ~C ８ Alkylene, or C ４ ~C ８ Forms alkenylenes; (a4) R １ and P １ R １ The carbon atom to which it is bonded, and P １ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle is further X １ It is replaced with X １ is R ６ Together with C ４ ~C ８ Alkylene, or C４ ~C ８ Forms alkenylenes; P １ R １ and P １ Unless it forms a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms or C １ ~C ６ It is alkyl, Q １ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ２ The formula is as follows: (In the formula, * represents R in formula (2)) ２ X represents the carbon atom to which it is bonded. ２１ (b1) X ２１ C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or Halo C １ ~C ６ It is alkyl; (b2)X ２１ is, X ２１ and X ２２ Together with the bonded carbon atoms, it forms a 3- to 8-membered saturated alicyclic ring: X ２２ is, X ２１ and X ２２ Unless it forms a 3- to 8-membered saturated alicyclic ring, a hydrogen atom or C １ ~C ６ It is alkyl, X ２３ is a hydrogen atom, or C １ ~C ６ It is represented as (alkyl), P ２ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ２ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ３ C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, C ６ ~C １４ Aryloxy C １ ~C ６ Alkyl, or C ７ ~C １４ It is an aralkyl, and each of them is a halogen, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; P ３ C is a hydrogen atom. １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, Q ３ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ４ (d1) is one of the following (d1) to (d3): (d1) R ４ C is a hydrogen atom. １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ Alkyl; (d2)R ４ and P ４ R ４ The carbon atom to which it is bonded, and P ４Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups more independently selected from the group consisting of aryl groups; (d3)R ４ and Q ４ R ４ and Q ４ P forms a 3- to 8-membered saturated alicyclic ring together with the bonded carbon atoms. ４ R ４ and P ４ Unless it forms a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms or C １ ~C ６ It is alkyl, Q ４ R ４ and Q ４ Except when forming a 3- to 8-membered saturated alicyclic ring, hydrogen atoms, C １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is an alkyl group, and each of them may be substituted with one or more halogens, R ５ is aminocarbonyl C １ ~C ６ Alkoxy C １~C ６ Alkyl (the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ C may be substituted with a cycloalkylamino or a 3- to 10-membered monocyclic cyclic amino, or a 4- to 7-membered heterocyclyl. １ ~C ６ Alkoxy C １ ~C ６ It is alkyl, P ５ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ５ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ６ R １ Unless (a3) ​​or (a4), the following formula (In the formula, ** represents R in formula (2)) ６ X represents the carbon atom to which it is bonded. ６１ (f1)X ６１ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, or C ３ ~C ８ It is a cycloalkoxy; (f2)X ６１ is, X ６１ and X ６２Together with the bonded carbon atoms, these atoms form a 3-8 member saturated alicyclic ring or a 4-7 member saturated heterocyclic ring, and these 3-8 member saturated alicyclic rings or 4-7 member saturated heterocyclic rings contain halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; X ６２ is, X ６１ and X ６２ Unless it forms a 3-8 member saturated alicyclic ring or a 4-7 member saturated heterocycle, a hydrogen atom or C １ ~C ６ It is alkyl; X ６３ is a hydrogen atom, or C １ ~C ６ It is represented as (alkyl), P ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ７ (h1)R ７ C １ ~C ６ It is alkyl; (h2)R ７ and P ７ R ７ The carbon atom to which it is bonded, and P ７ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered saturated heterocycle, and this 4- to 7-membered saturated heterocycle is a halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C１４ It may be substituted with one or more groups selected more independently from the group consisting of aryl groups; P ７ R ７ and P ７ Unless it forms a 4- to 7-membered saturated heterocycle, a hydrogen atom or C １ ~C ６ It is alkyl, Q ７ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ８ is either (i1) or (i2) below, and (i1) R ８ C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; (i2)R ８ and P ８ R ８ The carbon atom to which it is bonded, and P ８ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４The 4- to 7-membered monocyclic saturated heterocycle may be substituted with one or more groups more independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring; P ８ R ８ and P ８ Except when forming a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms, C １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, Q ８ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ９ C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, 4-7 member heterocyclyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkil, C ６ ~C １０ Aryloxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, 4-9 member heterocyclyloxy C １ ~C ６ Alkyl or 5-10 member heteroaryl C １ ~C ６The C is alkyl, and each of them may be substituted with a halogen. ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl and 5-10 membered heteroaryl C １ ~C ６ Alkyl is C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy and Halo C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys, P ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, R １０ is a hydrogen atom, or C １ ~C ６ It is alkyl, P １０ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C ７ ~C １４ It is aralkyl, and each of them may be substituted with one or more halogens, Q １０ is a hydrogen atom, or C １ ~C ６It is alkyl, R １１ C is a hydrogen atom. １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, aminocarbonyl (where the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ The aminocarbonyl is a cycloalkylamino or a 3-10 member monocyclic cyclic amino, and if the aminocarbonyl is a 3-10 member monocyclic cyclic aminocarbonyl, it may be condensed with a 3-8 member saturated alicyclic ring, or it may form a spiro ring or a crosslinking ring on the ring, and the aminocarbonyl may be a halogen, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ It may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups, P １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, L １１ It is either a single bond or -CM １１ M １２ -, - (CH ２ ) ｎ S (CH ２ ) ｍ-, -(CH ２ ) ｎ S(O)(CH ２ ) ｍ -, or -(CH ２ ) ｎ S(O) ２ (CH ２ ) ｍ -, and wherein n and m are each independently 1 or 2, and M １１ is a hydrogen atom or C １ -C ６ alkyl, and M １２ is a hydrogen atom or C １ -C ６ alkyl. [3] R １ is C １ -C ６ alkyl or C ２ -C ７ alkenyl, the compound or a salt thereof according to [1] or [2]. [4] R １ is C １ -C ６ alkyl, the compound or a salt thereof according to [1] or [2]. [5] R １ is methyl, the compound or a salt thereof according to [1] or [2]. [6] R １ and P １ together with the carbon atom to which R １ is bonded and the nitrogen atom to which P １ is bonded form a 4- to 7-membered saturated cyclic heterocycle, and the 4- to 7-membered saturated cyclic heterocycle is substituted with halogen, C １ -C ６ alkyl, C ２ -C ７ alkenyl, C １ -C ６ alkoxy, halo C １ -C ６ alkoxy, C １ -C ６ alkoxy C １ -C ６ alkyl and C ６ -C １４The compound or salt thereof according to [1] or [2], which may be substituted with one or more groups independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring. [7] The R １ and P １ The compound or a salt thereof according to [6], wherein the 4- to 7-membered monocyclic saturated heterocycle formed is a 5- to 6-membered monocyclic saturated heterocycle. [8] The R １ and P １ The compound or a salt thereof according to [6], wherein the 4- to 7-membered monocyclic saturated heterocycle formed is a 5-membered monocyclic saturated heterocycle. [9] The R １ and P １ The compound or salt thereof described in [6], wherein the 4- to 7-membered monocyclic saturated heterocycle formed is a pyrrolidine ring.

[10] R １ and P １ However, the following formula (In the formula, *** and **** are P in formula (1) or (2), respectively.) １ The nitrogen atom and R to which it is bonded １ X represents the carbon atom to which it is bonded. １ is a hydrogen atom, halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkoxy, or C ６ ~C １４ A compound or salt thereof according to [1] or [2], which forms a ring represented by an aryl compound. [10-1] X １ However, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or C ６ ~C １４ A compound or salt thereof described in

[10] , which is an aryl compound.

[11] X １ However, C １ ~C ６ A compound or salt thereof described in

[10] , which is alkyl.

[12] X １is methyl or ethyl, the compound or a salt thereof according to

[10] . [12-1] R １ , together with R ６ forms C ４ to C ８ alkylene or C ４ to C ８ alkenylene, the compound or a salt thereof according to [1] or [2]. [12-2] R １ , together with R ６ forms n-pentylene, the compound or a salt thereof according to [1] or [2]. [12-3] R １ and P １ , together with the carbon atom to which R １ is bonded and the nitrogen atom to which P １ is bonded, form a 4- to 7-membered monocyclic saturated heterocycle, and the 4- to 7-membered monocyclic saturated heterocycle is further substituted with X １ , and X １ , together with R ６ forms C ４ to C ８ alkylene or C ４ to C ８ alkenylene, the compound or a salt thereof according to [1] or [2]. [12-4] R １ and P １ , together with the carbon atom to which R １ is bonded and the nitrogen atom to which P １ is bonded, form a 4- to 7-membered monocyclic saturated heterocycle, and the 4- to 7-membered monocyclic saturated heterocycle is further substituted with X １ , and X １ , together with R ６ forms C ４ to C ８ alkylene or C ４ to C ８ alkenylene, the compound or a salt thereof according to [1] or [2]. [12-5] the 4- to 7-membered monocyclic saturated heterocycle is a pyrrolidine ring, and X １ , together with R ６ forms 2-butenylene or 2-pentenylene, the compound or a salt thereof according to any one of [1], [2], [12-3] and [12-4].

[13] P１ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to [5].

[14] P １ The compound or salt thereof described in any of [1] to [5], wherein the compound is methyl, ethyl, or n-propyl.

[15] Q １ However, a compound or salt thereof described in any of [1] to

[14] , which is a hydrogen atom.

[16] X ２３ However, a compound or salt thereof described in any of [1] to

[15] , which is a hydrogen atom.

[17] X ２１ However, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or Halo C １ ~C ６ It is alkyl, X ２２ However, C １ ~C ６ Alkyl; X ２３ is a hydrogen atom, and is a compound or salt thereof described in any of [1] to

[15] .

[18] X ２１ However, C １ ~C ６ It is alkyl, X ２２ However, C １ ~C ６ It is alkyl, X ２３ However, a compound or salt thereof described in any of [1] to

[15] , wherein the compound is a hydrogen atom.

[19] R ２ The compound or salt thereof according to any one of [1] to

[15] , wherein the compound is 1-methylpropyl, 1-methoxyethyl, 1-methylethyl, or ethyl.

[20] R ２ However, the compound or salt thereof described in any of [1] to

[15] is 1-methylpropyl.

[21] P ２ However, a compound or salt thereof described in any of [1] to

[20] , which is a hydrogen atom.

[22] Q ２ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[21] .

[23] R ３ However, C may be substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C１ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[22] . [23-1]R ３ However, C may be substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[22] .

[24] R ３ However, C may be substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[22] .

[25] R ３ However, C may be substituted with one or more halogens. ５ ~C ７ Cycloalkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[22] . [25-1]R ３ However, C may be substituted with one or more halogens. ５ ~C ７ Cycloalkoxy C １ ~C ２ A compound or salt thereof, which is alkyl, as described in any of [1] to

[22] .

[26] R ３ However, C may be substituted with one or more halogens. ６ Cycloalkoxy C １ ~C ６A compound or salt thereof, which is alkyl, as described in any of [1] to

[22] .

[27] R ３ The compound or salt thereof described in any of [1] to

[22] , wherein the compound is (cyclopentoxy)methyl, (cyclohexoxy)methyl, or (cycloheptoxy)methyl.

[28] P ３ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[27] .

[29] P ３ However, the compound or salt thereof described in any of [1] to

[27] is methyl.

[30] Q ３ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[29] .

[31] R ４ However, hydrogen atoms, C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[30] .

[32] R ４ and P ４ However, R ４ The carbon atom to which it is bonded, and P ４ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The compound or salt thereof according to any one of [1] to

[30] , which may be substituted with one or more groups selected more independently from the group consisting of aryls.

[33] The R ４ and P４ The compound or salt thereof according to

[32] , wherein the 4- to 7-membered monocyclic saturated heterocycle formed is a 5-membered monocyclic saturated heterocycle.

[34] The R ４ and P ４ The compound or salt thereof described in

[32] , wherein the 4- to 7-membered monocyclic saturated heterocycle formed is a pyrrolidine ring. [34-1]R ４ and Q ４ However, R ４ and Q ４ A compound or salt thereof according to any one of [1] to

[30] , wherein the compound forms a 3- to 8-membered saturated alicyclic ring together with the carbon atom to which it is bonded.

[35] P ４ However, C １ ~C ６ A compound or salt thereof described in

[31] or [34-1], which is alkyl.

[36] P ４ A compound or salt thereof described in any of [1] to

[31] , wherein the compound is methyl. [36-1]R ４ and P ４ However, R ４ The carbon atom to which it is bonded, and P ４ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, Q ４ However, hydrogen atoms, C １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, 5-10 member heteroaryl C １ ~C ６ Alkyl, Halo C １ ~C ６ C which may be substituted with alkyl or halogen ７ ~C １４ A compound or salt thereof described in any of [1] to

[36] that is aralkyl. [36-2]R ４ and P ４ However, R ４ The carbon atom to which it is bonded, and P ４Together with the nitrogen atom to which it is bonded, it forms an azetidine ring, a pyrrolidine ring, and a piperidine ring, Q ４ However, hydrogen atoms, C １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, 5-10 member heteroaryl C １ ~C ６ Alkyl, Halo C １ ~C ６ C which may be substituted with alkyl or halogen ７ ~C １４ A compound or salt thereof that is aralkyl, as described in any of [1] to

[36] . [36-3]R ４ and P ４ However, R ４ The carbon atom to which it is bonded, and P ４ Together with the nitrogen atom to which it is bonded, it forms a pyrrolidine ring, Q ４ The compound or salt thereof described in any of [1] to

[36] , wherein the compound is methyl, ethyl, 2-phenethyl, phenylmethyl, 2-fluorophenylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-propa-2-inyl, buta-2-inyl, 2-fluoroethyl, 2,2-difluoroethyl, or methoxymethyl.

[37] Q ４ However, hydrogen atoms, or C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[36] .

[38] Q ４ A compound or salt thereof described in any of [1] to

[36] , wherein the compound is methyl.

[39] R ５ However, aminocarbonyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl (the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ A compound or salt thereof according to any one of [1] to

[38] (which is a cycloalkylamino or a 3- to 10-membered monocyclic cyclic amino). [39-1]R ５ However, Mono C １ ~C ６ Alkylaminocarbonyl C １ ~C ２ Alkoxy C １ ~C ２ Alkyl or mono-C ３ ~C ８ Cycloalkylaminocarbonyl C １ ~C ２ Alkoxy C １ ~C ２ A compound or salt thereof, which is alkyl, as described in any of [1] to

[38] .

[40] R ５ However, Mono C １ ~C ６ Alkylaminocarbonyl C １ ~C ２ Alkoxy C １ ~C ２ A compound or salt thereof, which is alkyl, as described in any of [1] to

[38] .

[41] R ５ However, ((t-butylamino)carbonyl]methoxymethyl, the compound or salt thereof described in any of [1] to

[38] .

[42] P ５ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[41] .

[43] Q ５ However, a compound or salt thereof described in any of [1] to

[42] , which is a hydrogen atom.

[44] X ６１ However, hydrogen atoms, C １ ~C ６ Alkyl, C２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, or C ３ ~C ８ It is a cycloalkoxy, X ６２ However, C １ ~C ６ It is alkyl, X ６３ However, a compound or salt thereof described in any of [1] to

[43] , which is a hydrogen atom.

[45] X ６１ and X ６２ However, X ６１ and X ６２ Together with the bonded carbon atoms, it forms a 4-6 membered saturated alicyclic ring, X ６３ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[43] .

[46] P ６ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[45] .

[47] P ６ A compound or salt thereof according to any of [1] to

[45] , wherein the compound is methyl or ethyl.

[48] P ６ However, the compound or salt thereof described in any of [1] to

[45] , which is methyl.

[49] Q ６ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[48] .

[50] R ７ However, C １ ~C ３ Is it alkyl, or R ７ and P ７ However, R ７ The carbon atom to which it is bonded, and P ７ Together with the bonded nitrogen atom, it forms a 4- or 5-membered saturated heterocycle, and this 4- or 5-membered saturated heterocycle is a halogen and C １ ~C ６ A compound or salt thereof according to any one of [1] to

[49] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[51] R ７ However, C １ ~C ３A compound or salt thereof, which is alkyl, as described in any of [1] to

[50] .

[52] R ７ A compound or salt thereof described in any of [1] to

[50] , wherein the compound is methyl.

[53] R ７ and P ７ However, R ７ The carbon atom to which it is bonded, and P ７ Together with the bonded nitrogen atom, it forms a 4- or 5-membered saturated heterocycle, and this 4- or 5-membered saturated heterocycle is a halogen and C １ ~C ６ The compound or salt thereof according to any one of [1] to

[50] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[54] The R ７ and P ７ The compound or salt thereof according to

[53] , wherein the 4 or 5-membered saturated heterocycle formed is a 5-membered saturated heterocycle.

[55] The R ７ and P ７ The compound or salt thereof according to

[53] , wherein the 4 or 5-membered saturated heterocycle formed is a pyrrolidine ring.

[56] P ７ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[52] . [56-1]P ７ However, the compound or salt thereof described in any of [1] to

[52] is methyl.

[57] Q ７ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[56] .

[58] R ８ However, C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６A compound or salt thereof according to any one of [1] to

[57] , which may be substituted with one or more groups independently selected from the group consisting of alkoxys.

[59] R ８ However, C ３ ~C ８ A cycloalkyl compound or a salt thereof, as described in any of [1] to

[57] . [59-1]R ８ However, C ３ ~C ８ It is a cycloalkyl, P ８ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[57] . [59-2]R ８ However, it is cyclopropyl, and P ８ The compound or salt thereof according to any one of [1] to

[57] , wherein the compound is methyl, ethyl, n-propyl, i-propyl, n-butyl, or 2-methylpropyl.

[60] R ８ However, the compound or salt thereof described in any of [1] to

[57] is cyclopropyl.

[61] R ８ and P ８ However, R ８ The carbon atom to which it is bonded, and P ８ The compound or salt thereof according to any one of [1] to

[57] , wherein the R forms a 4- to 7-membered monocyclic saturated heterocycle together with the nitrogen atom to which it is bonded, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring.

[62] The R ８ and P ８ The compound or salt thereof described in

[61] , wherein the 4- to 7-membered monocyclic saturated heterocycle formed is an azepane ring.

[63] P ８ However, C １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[60] .

[64] P ８ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[60] .

[65] P８ The compound or salt thereof according to any one of [1] to

[60] , wherein the compound is methyl, ethyl, n-propyl, i-propyl, n-butyl, or 2-methylpropyl.

[66] P ８ The compound or salt thereof according to any one of [1] to

[60] , wherein the compound is ethyl or n-propyl.

[67] Q ８ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[66] .

[68] R ９ However, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is alkyl, and the C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ Alkyls are halogens, and C １ ~C ６ A compound or salt thereof according to any one of [1] to

[67] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[69] R ９ However, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is alkyl, and the C ７ ~C １４Aralkyl, or 5-10 member heteroaryl C １ ~C ６ Alkyls are halogens, and C １ ~C ６ A compound or salt thereof according to any one of [1] to

[67] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups. [69-1]R ９ However, C ６ Aryl C １ ~C ２ Alkyl or 6-membered heteroaryl C １ ~C ２ It is alkyl, and the C ６ Aryl C １ ~C ２ Alkyl or 6-membered heteroaryl C １ ~C ２ Alkyls are halogens, and C １ ~C ６ A compound or salt thereof according to any one of [1] to

[67] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[70] R ９ The compound or salt thereof described in any of [1] to

[67] , wherein the compound is 2-phenylethyl, 2-(2-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, (3-fluoro-4-pyridyl)ethyl, or (3-chloro-4-pyridyl)ethyl.

[71] P ９ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[70] .

[72] P ９ A compound or salt thereof according to any one of [1] to

[70] , wherein the compound is methyl or ethyl.

[73] P ９ However, the compound or salt thereof described in any of [1] to

[70] is methyl.

[74] Q ９ However, a compound or salt thereof described in any of [1] to

[73] , which is a hydrogen atom.

[75] R １０ However, a compound or salt thereof described in any of [1] to

[74] , which is a hydrogen atom.

[76] P １０ However, C may be substituted with one or more halogens.１ ~C ６ Alkyl, or C ２ ~C ６ A compound or salt thereof described in any of [1] to

[75] , which is an alkenyl.

[77] P １０ However, C may be substituted with one or more halogens. １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[75] .

[78] P １０ The compound or salt thereof according to any one of [1] to

[75] , wherein the compound is ethyl, n-butyl, or n-propyl.

[79] Q １０ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[78] .

[80] R １１ However, it is a 3-10 member monocyclic cyclic aminocarbonyl, and the 3-10 member monocyclic cyclic aminocarbonyl may be condensed with a 3-8 member saturated alicyclic ring, and may form a spiro ring or a crosslinking ring on the ring, and the atoms forming the ring of the 3-10 member monocyclic cyclic aminocarbonyl are halogens, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ A compound or salt thereof according to any one of [1] to

[79] , which may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups.

[81] R １１ However, it is a 4 or 5-membered monocyclic cyclic aminocarbonyl, and the 4 or 5-membered monocyclic cyclic aminocarbonyl may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl are halogens, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８A compound or salt thereof according to any one of [1] to

[79] , which may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups.

[82] R １１ However, it is a 4 or 5-membered monocyclic cyclic aminocarbonyl, and the 4 or 5-membered monocyclic cyclic aminocarbonyl may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl are one or more halogens and one or more C １ ~C ６ A compound or salt thereof according to any one of [1] to

[79] , which may be substituted with an alkyl group. [82-1]R １１ The compound or salt thereof according to any one of [1] to

[79] , wherein is a 4 or 5-membered monocyclic cyclic aminocarbonyl, the 4 or 5-membered monocyclic cyclic aminocarbonyl may form a spiroring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl may be substituted with one or two substituents selected from fluorine, methyl, ethyl, propyl, and methoxy. [82-2]R １１ The compound or salt thereof according to any one of [1] to

[79] , wherein is a 4 or 5-membered monocyclic cyclic aminocarbonyl, the 4 or 5-membered monocyclic cyclic aminocarbonyl may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl may be substituted with one substituent selected from fluorine, methyl, ethyl, propyl, and methoxy, or with two substituents selected from a combination of methyl and methyl, a combination of methyl and fluorine, a combination of ethyl and fluorine, a combination of fluorine and fluorine, a combination of methyl and methoxy, and a combination of methyl and ethyl. [82-3]R １１The compound or salt thereof according to any one of [1] to

[79] , wherein is a 4 or 5-membered monocyclic cyclic aminocarbonyl, and the 4 or 5-membered monocyclic cyclic aminocarbonyl is (azetidine-1-yl)carbonyl or (pyrrolidine-1-yl)carbonyl, and the carbon atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl may be substituted with one or two substituents selected from fluorine, methyl, ethyl, propyl, and methoxy.

[83] R １１ However, (3-ethylazetidine-1-yl)carbonyl, (2,2-dimethylazetidine-1-yl)carbonyl, (3-fluoro-3-methylazetidine-1-yl)carbonyl, (3-ethyl-3-fluoroazetidine-1-yl)carbonyl, (3,3-dimethylazetidine-1-yl)carbonyl, (3-ethyl-3-methylazetidine-1-yl)carbonyl, (2-azaspiro[3,3]heptan-2-yl)carbonyl, (2- A compound or salt thereof described in any of [1] to

[79] , which is azaspiro[3,4]octan-2-yl)carbonyl, (3,3-difluoropyrrolidine-1-yl)carbonyl, (3,3-dimethylpyrrolidine-1-yl)carbonyl, (3-azabicyclo[3.2.0]heptan-3-yl)carbonyl, (5-azspiro[2,4]heptan-5-yl)carbonyl, or (6-azspiro[3,4]octan-6-yl)carbonyl.

[84] P １１ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[83] .

[85] Q １１ However, a hydrogen atom, the compound or salt thereof described in any of [1] to

[84] .

[86] L １１ However, -CM １１ M １２ - and M １１ However, hydrogen atoms, or C １ ~C ６ It is alkyl, M １２ However, hydrogen atoms, or C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of [1] to

[85] .

[87] L １１ However, -CH ２- A compound or salt thereof as described in any of [1] to

[85] .

[88] P １ ~P １１ A compound or salt thereof according to any of [1] to

[87] , wherein at least four of the atoms are not hydrogen atoms.

[89] P １ ~P １１ A compound or salt thereof according to any of [1] to

[87] , wherein at least five of the atoms are not hydrogen atoms.

[90] P １ ~P １１ A compound or salt thereof according to any of [1] to

[87] , wherein at least six of the atoms are not hydrogen atoms.

[91] P １ ~P １１ A compound or salt thereof according to any of [1] to

[87] , wherein at least seven of the atoms are not hydrogen atoms.

[92] P １ ~P １１ A compound or salt thereof described in any of [1] to

[87] , wherein at least eight of the atoms are not hydrogen atoms.

[93] A compound or salt thereof represented by the following formula (3): In the formula, １ C is a hydrogen atom. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or C ６ ~C １４ It is aryl, n is 1 or 2, R ２ The formula is as follows: (In the formula, * represents R in formula (3)) ２ X represents the carbon atom to which it is bonded. ２１ (b1) X ２１ C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or Halo C １ ~C ６ It is alkyl; (b2)X ２１ is, X ２１ and X ２２ Together with the bonded carbon atoms, it forms a 3- to 8-membered saturated alicyclic ring: X ２２ is, X ２１ and X ２２Unless it forms a 3- to 8-membered saturated alicyclic ring, a hydrogen atom or C １ ~C ６ It is alkyl, P ２ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ２ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ３ C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, C ６ ~C １４ Aryloxy C １ ~C ６ Alkyl, or C ７ ~C １４ It is an aralkyl, and each of them is a halogen, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys, P ３ C is a hydrogen atom. １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, Q ３ is a hydrogen atom, or C １~C ６ It is alkyl, Q ４ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is an alkyl group, and each of them may be substituted with one or more halogens, X ５ C １ ~C ６ Alkyl, or C １ ~C ６ C may be substituted with alkyl. ３ ~C ８ It is a cycloalkyl, R ６ The formula is as follows: (In the formula, ** represents R in formula (3)) ６ X represents the carbon atom to which it is bonded. ６１ (f1)X ６１ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, or C ３ ~C ８ It is a cycloalkoxy; (f2)X ６１ is, X ６１ and X ６２ Together with the bonded carbon atoms, these atoms form a 3-8 member saturated alicyclic ring or a 4-7 member saturated heterocyclic ring, and these 3-8 member saturated alicyclic rings or 4-7 member saturated heterocyclic rings contain halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; X ６２ is, X ６１and X ６２ Unless it forms a 3- to 8-membered saturated alicyclic ring or a 4- to 7-membered saturated heterocyclic ring, a hydrogen atom or C １ ~C ６ It is alkyl; X ６３ is a hydrogen atom, or C １ ~C ６ It is represented as (alkyl), P ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ７ (h1)R ７ C １ ~C ６ It is alkyl; (h2)R ７ and P ７ R ７ The carbon atom to which it is bonded, and P ７ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered saturated heterocycle, and this 4- to 7-membered saturated heterocycle is a halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups selected more independently from the group consisting of aryl groups; P ７ R ７ and P ７ Unless it forms a 4- to 7-membered saturated heterocycle, a hydrogen atom or C １ ~C ６ It is alkyl, Q ７ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ８is either (i1) or (i2) below, and (i1) R ８ C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; (i2)R ８ and P ８ R ８ The carbon atom to which it is bonded, and P ８ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The 4- to 7-membered monocyclic saturated heterocycle may be substituted with one or more groups more independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring; P ８ R ８ and P ８ Except when forming a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms, C １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, Q８ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ９ C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, 4-7 member heterocyclyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkil, C ６ ~C １０ Aryloxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, 4-9 member heterocyclyloxy C １ ~C ６ Alkyl or 5-10 member heteroaryl C １ ~C ６ The C is alkyl, and each of them may be substituted with a halogen. ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl and 5-10 membered heteroaryl C １ ~C ６ Alkyl is C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Alkoxy and Halo C１ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys, P ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, P １０ C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C ７ ~C １４ It is aralkyl, and each of them may be substituted with one or more halogens, R １１ C is a hydrogen atom. １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, aminocarbonyl (where the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８The aminocarbonyl is a cycloalkylamino or a 3-10 member monocyclic cyclic amino, and if the aminocarbonyl is a 3-10 member monocyclic cyclic aminocarbonyl, it may be condensed with a 3-8 member saturated alicyclic ring, or it may form a spiro ring or a crosslinking ring on the ring, and the aminocarbonyl may be a halogen, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ It may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups, P １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q １１ is a hydrogen atom, or C １ ~C ６ It is alkyl. [93-1] The compound or salt thereof described in

[93] , wherein n is 1.

[94] The compound or salt thereof represented by the following formula (4): In the formula, １ C is a hydrogen atom. １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or C ６ ~C １４ It is aryl, R ２ The formula is as follows: (In the formula, * represents R in formula (4)) ２ X represents the carbon atom to which it is bonded. ２１ (b1) X ２１ C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or Halo C １ ~C ６ It is alkyl; (b2)X ２１ is, X ２１ and X ２２ Together with the bonded carbon atoms, it forms a 3- to 8-membered saturated alicyclic ring: X ２２ is, X２１ and X ２２ Unless it forms a 3- to 8-membered saturated alicyclic ring, a hydrogen atom or C １ ~C ６ It is alkyl, P ２ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ２ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ３ C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, C ６ ~C １４ Aryloxy C １ ~C ６ Alkyl, or C ７ ~C １４ It is an aralkyl, and each of them is a halogen, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys, P ３ C is a hydrogen atom. １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, Q３ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ４ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is an alkyl group, and each of them may be substituted with one or more halogens, X ５ C １ ~C ６ Alkyl, or C １ ~C ６ C may be substituted with alkyl. ３ ~C ８ It is a cycloalkyl, R ６ The formula is as follows: (In the formula, ** represents R in formula (4)) ６ X represents the carbon atom to which it is bonded. ６１ (f1)X ６１ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, or C ３ ~C ８ It is a cycloalkoxy; (f2)X ６１ is, X ６１ and X ６２ Together with the bonded carbon atoms, these atoms form a 3-8 member saturated alicyclic ring or a 4-7 member saturated heterocyclic ring, and these 3-8 member saturated alicyclic rings or 4-7 member saturated heterocyclic rings contain halogens, C １ ~C ６ Alkyl and C １ ~C ６It may be substituted with one or more groups independently selected from the group consisting of alkoxys; X ６２ is, X ６１ and X ６２ Unless it forms a 3- to 8-membered saturated alicyclic ring or a 4- to 7-membered saturated heterocyclic ring, a hydrogen atom or C １ ~C ６ It is alkyl; X ６３ is a hydrogen atom, or C １ ~C ６ It is represented as (alkyl), P ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ７ (h1)R ７ C １ ~C ６ It is alkyl; (h2)R ７ and P ７ R ７ The carbon atom to which it is bonded, and P ７ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered saturated heterocycle, and this 4- to 7-membered saturated heterocycle is a halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups selected more independently from the group consisting of aryl groups; P ７ R ７ and P ７ Unless it forms a 4- to 7-membered saturated heterocycle, a hydrogen atom or C １ ~C ６ It is alkyl, Q ７ is a hydrogen atom, or C１ ~C ６ It is alkyl, R ８ is either (i1) or (i2) below, and (i1) R ８ C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; (i2)R ８ and P ８ R ８ The carbon atom to which it is bonded, and P ８ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The 4- to 7-membered monocyclic saturated heterocycle may be substituted with one or more groups more independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring; P ８ R ８ and P ８ Except when forming a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms, C １ ~C ６ Alkyl, or C ３ ~C ８Cycloalkyl C １ ~C ６ It is alkyl, Q ８ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ９ C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, 4-7 member heterocyclyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkil, C ６ ~C １０ Aryloxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, 4-9 member heterocyclyloxy C １ ~C ６ Alkyl or 5-10 member heteroaryl C １ ~C ６ The C is alkyl, and each of them may be substituted with a halogen. ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl and 5-10 membered heteroaryl C １ ~C ６ Alkyl is C １ ~C ６ Alkyl, C １ ~C ６Haloalkyl, C １ ~C ６ Alkoxy and Halo C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys, P ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, P １０ C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C ７ ~C １４ It is aralkyl, and each of them may be substituted with one or more halogens, R １１ C is a hydrogen atom. １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, aminocarbonyl (where the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C８ Cycloalkylamino, diC ３ ~C ８ The aminocarbonyl is a cycloalkylamino or a 3-10 member monocyclic cyclic amino, and if the aminocarbonyl is a 3-10 member monocyclic cyclic aminocarbonyl, it may be condensed with a 3-8 member saturated alicyclic ring, or it may form a spiro ring or a crosslinking ring on the ring, and the aminocarbonyl may be a halogen, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ It may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups, P １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q １１ is a hydrogen atom, or C １ ~C ６ It is alkyl.

[95] X １ However, C １ ~C ６ A compound or salt thereof described in

[93] or

[94] , which is alkyl.

[96] X １ The compound or salt thereof described in

[93] or

[94] , wherein the compound is methyl or ethyl.

[97] X ２１ However, C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or Halo C １ ~C ６ It is alkyl, X ２２ However, C １ ~C ６ It is alkyl, X ２３ However, a compound or salt thereof described in any of

[93] to

[96] , which is a hydrogen atom.

[98] X ２１ However, C １ ~C ６ It is alkyl, X ２２ However, C １ ~C ６ It is alkyl, X ２３However, a compound or salt thereof described in any of

[93] to

[96] , which is a hydrogen atom.

[99] R ２ The compound or salt thereof according to any one of

[93] to

[96] , wherein the compound is 1-methylpropyl, 1-methoxyethyl, 1-methylethyl, or ethyl.

[100] R ２ However, the compound or salt thereof described in any of

[93] to

[96] is 1-methylpropyl.

[101] P ２ However, a hydrogen atom, the compound or salt thereof described in any of

[93] to

[100] .

[102] Q ２ However, a compound or salt thereof described in any of

[93] to

[101] , which is a hydrogen atom.

[103] R ３ However, C may be substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[102] . [103-1]R ３ However, C may be substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[102] .

[104] R ３ However, C may be substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[102] .

[105] R ３However, C may be substituted with one or more halogens. ５ ~C ７ Cycloalkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[102] .

[106] R ３ However, C may be substituted with one or more halogens. ６ Cycloalkoxy C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[102] .

[107] R ３ The compound or salt thereof described in any of

[93] to

[102] , wherein the compound is (cyclopentoxy)methyl, (cyclohexoxy)methyl, or (cycloheptoxy)methyl.

[108] P ３ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[107] .

[109] P ３ However, a compound or salt thereof described in any of

[93] to

[107] , which is methyl.

[110] Q ３ However, a hydrogen atom, the compound or salt thereof described in any of

[93] to

[109] .

[111] Q ４ However, hydrogen atoms, or C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[110] .

[112] Q ４ A compound or salt thereof described in any of

[93] to

[110] , which is methyl.

[113] X ５ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[112] .

[114] X ５ However, the compound or salt thereof described in any of

[93] to

[112] is t-butyl.

[115] X ６１ However, hydrogen atoms, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６Alkoxy, or C ３ ~C ８ It is a cycloalkoxy, X ６２ However, C １ ~C ６ It is alkyl, X ６３ However, a compound or salt thereof described in any of

[93] to

[114] , which is a hydrogen atom.

[116] X ６１ and X ６２ However, X ６１ and X ６２ Together with the bonded carbon atoms, it forms a 4-6 membered saturated alicyclic ring, X ６３ However, a hydrogen atom, the compound or salt thereof described in any of

[93] to

[114] .

[117] P ６ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[116] .

[118] P ６ A compound or salt thereof according to any of

[93] to

[116] , wherein the compound is methyl or ethyl.

[119] P ６ A compound or salt thereof described in any of

[93] to

[116] , which is methyl.

[120] R ７ However, C １ ~C ３ Is it alkyl, or R ７ and P ７ However, R ７ The carbon atom to which it is bonded, and P ７ Together with the bonded nitrogen atom, it forms a 4- or 5-membered saturated heterocycle, and this 4- or 5-membered saturated heterocycle is a halogen and C １ ~C ６ A compound or salt thereof according to any one of

[93] to

[119] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[121] R ７ However, C １ ~C ３ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[120] .

[122] R ７ A compound or salt thereof, described in any of

[93] to

[120] , which is methyl.

[123] R ７ and P ７ However, R７ The carbon atom to which it is bonded, and P ７ Together with the bonded nitrogen atom, it forms a 4- or 5-membered saturated heterocycle, and this 4- or 5-membered saturated heterocycle is a halogen and C １ ~C ６ The compound or salt thereof according to any one of

[93] to

[120] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[124] The R ７ and P ７ The compound or salt thereof according to

[123] , wherein the 4 or 5-membered saturated heterocycle formed is a 5-membered saturated heterocycle.

[125] The R ７ and P ７ The compound or salt thereof according to

[123] , wherein the 4 or 5-membered saturated heterocycle formed is a pyrrolidine ring.

[126] P ７ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[122] . [126-1]P ７ However, a compound or salt thereof described in any of

[93] to

[122] , which is methyl.

[127] Q ７ However, a hydrogen atom, the compound or salt thereof described in any of

[93] to

[126] .

[128] R ８ However, C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６ A compound or salt thereof according to any one of

[93] to

[127] , which may be substituted with one or more groups independently selected from the group consisting of alkoxys.

[129] R ８ However, C ３ ~C ８ A cycloalkyl compound or a salt thereof, as described in any of

[93] to

[127] .

[130] R８ However, the compound or salt thereof described in any of

[93] to

[127] is cyclopropyl.

[131] R ８ and P ８ However, R ８ The carbon atom to which it is bonded, and P ８ A compound or salt thereof according to any one of

[93] to

[127] , wherein the nitrogen atom to which the compound is bonded forms a 4- to 7-membered monocyclic saturated heterocycle, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring.

[132] A compound or salt thereof according to

[131] , wherein the 4- to 7-membered monocyclic saturated heterocycle is an azepane ring.

[133] P ８ However, C １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[130] . ​​

[134] P ８ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[130] . ​​

[135] P ８ The compound or salt thereof according to any one of

[93] to

[130] , wherein the compound is methyl, ethyl, n-propyl, i-propyl, n-butyl, or 2-methylpropyl.

[136] P ８ The compound or salt thereof described in any of

[93] to

[130] , wherein the compound is ethyl or n-propyl.

[137] Q ８ However, a hydrogen atom, the compound or salt thereof described in any of

[93] to

[136] .

[138] R ９ However, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C１４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is alkyl, and the C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ Alkyls are halogens, and C １ ~C ６ A compound or salt thereof according to any one of

[93] to

[137] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[139] R ９ However, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is alkyl, and the C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ Alkyls are halogens, and C １ ~C ６ A compound or salt thereof according to any one of

[93] to

[137] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups. [139-1]R ９ However, C ６ Aryl C １ ~C ２ Alkyl or 6-membered heteroaryl C １ ~C ２ It is alkyl, and the C ６ Aryl C １ ~C ２ Alkyl or 6-membered heteroaryl C １ ~C ２ Alkyls are halogens, and C １ ~C ６A compound or salt thereof according to any one of

[93] to

[137] , which may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[140] R ９ The compound or salt thereof described in any of

[93] to

[137] , wherein the compound is 2-phenylethyl, 2-(2-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, (3-fluoro-4-pyridyl)ethyl, or (3-chloro-4-pyridyl)ethyl.

[141] P ９ However, C １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[140] .

[142] P ９ A compound or salt thereof described in any of

[93] to

[140] , wherein the compound is methyl or ethyl.

[143] P ９ However, a compound or salt thereof described in any of

[93] to

[140] , which is methyl.

[144] Q ９ However, a hydrogen atom, the compound or salt thereof described in any of

[93] to

[143] .

[145] R １０ However, a hydrogen atom, the compound or salt thereof described in any of

[93] to

[144] .

[146] P １０ However, C may be substituted with one or more halogens. １ ~C ６ Alkyl, or C ２ ~C ６ A compound or salt thereof, which is an alkenyl, as described in any of

[93] to

[145] .

[147] P １０ However, C may be substituted with one or more halogens. １ ~C ６ A compound or salt thereof, which is alkyl, as described in any of

[93] to

[145] .

[148] P １０ The compound or salt thereof described in any of

[93] to

[145] , wherein the compound is ethyl, n-butyl, or n-propyl.

[149] Q １０ However, a compound or salt thereof described in any of

[93] to

[148] , which is a hydrogen atom.

[150] R １１However, it is a 3-10 member monocyclic cyclic aminocarbonyl, and the 3-10 member monocyclic cyclic aminocarbonyl may be condensed with a 3-8 member saturated alicyclic ring, and may form a spiro ring or a crosslinking ring on the ring, and the atoms forming the ring of the 3-10 member monocyclic cyclic aminocarbonyl are halogens, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ A compound or salt thereof according to any one of

[93] to

[149] , which may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups.

[151] R １１ However, it is a 4 or 5-membered monocyclic cyclic aminocarbonyl, and the 4 or 5-membered monocyclic cyclic aminocarbonyl may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl are halogens, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ A compound or salt thereof according to any one of

[93] to

[149] , which may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups.

[152] R １１ However, it is a 4 or 5-membered monocyclic cyclic aminocarbonyl, and the 4 or 5-membered monocyclic cyclic aminocarbonyl may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl are one or more halogens and C １ ~C ６ A compound or salt thereof, which may be substituted with an alkyl group, as described in any of

[93] to

[149] . [152-1]R １１The compound or salt thereof according to any one of

[93] to

[149] , wherein is a 4 or 5-membered monocyclic cyclic aminocarbonyl, the 4 or 5-membered monocyclic cyclic aminocarbonyl may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl may be substituted with one or two substituents selected from fluorine, methyl, ethyl, propyl, and methoxy. [152-2]R １１ The compound or salt thereof according to any one of

[93] to

[149] , wherein is a 4 or 5-membered monocyclic cyclic aminocarbonyl, the 4 or 5-membered monocyclic cyclic aminocarbonyl may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl may be substituted with one substituent selected from fluorine, methyl, ethyl, propyl, and methoxy, or with two substituents selected from a combination of methyl and methyl, a combination of methyl and fluorine, a combination of ethyl and fluorine, a combination of fluorine and fluorine, a combination of methyl and methoxy, and a combination of methyl and ethyl.

[153] R １１ However, (3-ethylazetidine-1-yl)carbonyl, (2,2-dimethylazetidine-1-yl)carbonyl, (3-fluoro-3-methylazetidine-1-yl)carbonyl, (3-ethyl-3-fluoroazetidine-1-yl)carbonyl, (3,3-dimethylazetidine-1-yl)carbonyl, (3-ethyl-3-methylazetidine-1-yl), (2-azaspiro[3,3]heptan-2-yl)carbonyl, (2-azaspiro A compound or salt thereof described in any of

[93] to

[149] , which is (ro[3,4]octan-2-yl)carbonyl, (3,3-difluoropyrrolidine-1-yl)carbonyl, (3,3-dimethylpyrrolidine-1-yl)carbonyl, (3-azabicyclo[3.2.0]heptan-3-yl)carbonyl, (5-azaspiro[2,4]heptan-5-yl)carbonyl, or (6-azaspiro[3,4]octan-6-yl)carbonyl.

[154] P １１ However, a compound or salt thereof described in any of

[93] to

[153] , which is a hydrogen atom.

[155] Q １１However, a hydrogen atom, the compound or salt thereof described in any of

[93] to

[154] .

[156] The compound or salt thereof described in [1], selected from the compounds described in Table 17.

[157] Table 17 lists pp1-106, pp1-108, pp1-110, pp1-134, pp1-136, pp1-151, pp1-153, pp1-180, pp1-203, pp1-210, pp1-211, pp1-230, pp1-239, pp1-249, pp1-277, pp1-283, pp1-288, pp1-293, pp1-295, pp1-297, pp1-298, pp1-310, pp1-312, pp1-313, pp1-317, pp1-320, pp1-325, pp1-32 7. A compound or salt thereof described in [1], selected from the group consisting of pp1-340, pp1-349, pp1-351, pp1-352, pp1-364, pp1-365, pp1-369, pp1-377, pp1-381, pp1-421, pp1-425, pp1-428, pp1-443, pp1-446, pp3-010, pp3-011, pp3-033, pp3-036, pp3-037, pp3-039, pp4-009, pp4-011, pp5-003, pp5-004, and pp5-007.

[158] 2-[[(1S,4S,7S,13R,16S,19S,25S,33S,36S,42S,46S,51S)-42-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-6,13,18,35-tetramethyl-2,5,8,14,17,20,26,34,37,40,44-undecaoxo-36-(2-phenylethyl)-38-propyl-3,6,9,15,18,21,27,35,38,41,45-undecazahexacyclo[43.7.0.0 9,13 .0 21,25 .0 27,33 .0 46,51]dopentacontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propyl-33-prop-2-inyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46]heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,23S,28S,34S,37S,40S)-28-(2-azaspiro[3,3]heptan-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(2-cyclohexylethyl)-3-cyclopentyl-37-cyclopropyl-34-[2-(3-fluoro Pyridine-4-yl)ethyl]-23-methoxy-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32-prop-2-enyl-38-propyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-3-cyclopentyl-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-19-cyclobutyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-33-ethyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-27-ethyl-6,13,18,30-tetramethyl-31-(3-methylbutyl)-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46[Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,22S,25S,28S,34S,38S,43S)-34-(2-azaspiro[3,3]heptan-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-25-cyclopropyl-28-[2- (3-Fluoropyridine-4-yl)ethyl]-6,13,18,21,22,27-Hexamethyl-2,5,8,14,17,20,23,26,29,32,36-Undekaoxo-24,30-Dipropyl-3,6,9,15,18,21,24,27,30,33,37-Undekazatetracyclo[35.7.0.0 9,13 .0 38,43]Tetratetracontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-33-(2,2-difluoroethyl)-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-33-(3-fluoropropyl)-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46[Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,43S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-19-cyclobutyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-6,13,18,30,43-pentamethyl-2,5,8,14,17,20,26,29,32,35,39-undekaoxo-31-(2-phenylethyl)-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undekazatetracyclo[38.4.0.0 9,13 .0 21,25 ]Tetratetracontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-3,18-bis[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-31-[2-(3-fluoropyridine-4-yl)ethyl]-4-[(1R)-1-methoxyethyl]-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-37-cyclopropyl-24-ethyl-28-(3-fluoro-3-methylazetidine-1-carbonyl)-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-15-(3-methylbutoxymethyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-15-(2-methylpropoxymethyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-16,24-diethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-34-[2-(3-flu Olopyridine-4-yl)ethyl]-3-[(1S)-1-methoxyethyl]-4,9,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-3-[(1S)-1-ethoxyethyl]-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-34-(3,3,3-trifluoropropyl)-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-37-cyclopropyl-3-[(1S)-1-ethoxyethyl]-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-15-(3-methylbutoxymethyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-16,24-diethyl-28-(3-fluoro-3-methylazetidine-1-carbonyl)-4,9,35-trimethyl-34-(2-methylpropoxymethyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-3,18-bis[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-34-(2,2,2-trifluoroethoxymethyl)-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,16,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,16,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9S,12S,16S,22S,25S,28S,31S,34S,37R)-6-[(2S)-butane-2-yl]-31-cyclohexyl-3-(cyclohexyloxymethyl)-25-cyclopropyl-12-ethyl-16-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,23,28,29,32,37-hexamethyl-2,5,8,14,18,21,24,27,30,33,36-undecaoxo-22-(2-phenylethyl)-20,26-dipropyl-1,4,7,13,17,20,23,26,29,32,35-undecazatricyclo[35.3.0.0 9,13 ]Tetracontan-34-yl]methoxy]-N-tert-butylacetamide, N-tert-butyl-2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-18,24-diethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxyacetamide, N-tert-butyl-2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-18-(2-methylpropyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .021,25 ]tritetracontan-6-yl]methoxyacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-3-cyclopentyl-37-cyclopropyl-28-(3,3-dimethylazetidine-1-carbonyl)-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(cycloheptyloxymethyl)-37-cyclopropyl-34-[2-(4-fluorophenyl)ethyl]-4,9,16,24,35-pentamethyl-2,5,8,14,17,20,26,30,33,36,39-undekaoxo-3-propane-2-yl-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undekazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-34-[2-(3-chloropyridine-4-yl)ethyl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-3,18-bis[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-fluoro-3-methylazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,22S,25S,28S,34S,38S,43S)-4-[(2S)-butane-2-yl]-7-(cycloheptyloxymethyl)-19-cyclohexyl-25-cyclopropyl-34-(3-ethylazetidine-1-carbonyl)-28-[2-(3-fluoropyridine-4-yl)ethyl]-6,13,18,21,22,27-hexamethyl-2,5,8,14,17,20,23,26,29,32,36-undecaoxo-24,30-dipropyl-3,6,9,15,18,21,24,27,30,33,37-undecazatetracyclo[35.7.0.0 9,13 .0 38,43 ]Tetratetracontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-31-[2-(3-chloropyridine-4-yl)ethyl]-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46[Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-19-cyclohexyl-7-(cyclopentyloxymethyl)-28-cyclopropyl-27-ethyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-31-[2-(3-chloropyridine-4-yl)ethyl]-19-cyclobutyl-7-(2-cyclohexylethyl)-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46[Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-4-[(2S)-butane-2-yl]-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-37-(3,3-difluoropyrrolidine-1-carbonyl)-27-ethyl-31-[2-(2-fluorophenyl)ethyl]-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S)-4-[(2S)-butane-2-yl]-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-37-(3-ethyl-3-fluoroazetidine-1-carbonyl)-31-[2-(3-fluoropyridine-4-yl)ethyl]-6,13,18,30,42,42-hexamethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-43-oxa-3,6,9,15,18,21,27,30,33,36,40-undecazatetracyclo[38.4.0.0 9,13 .0 21,25]Tetratetracontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-28-(3,3-dimethylpyrrolidine-1-carbonyl)-24-ethyl-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-31-[2-(3-fluoropyridine-4-yl)ethyl]-6,18,30-trimethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46[Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-fluoro-3-methylazetidine-1-carbonyl)-4,9,16,35-tetramethyl-34-[2-(1-methylcyclopropyl)ethyl]-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-4-[(2S)-butane-2-yl]-7-(cycloheptyloxymethyl)-19-cyclohexyl-28-cyclopropyl-37-(3-ethyl-3-fluoroazetidine-1-carbonyl)-31-[2-(3-fluoropyridine-4-yl)ethyl]-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46[Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(5-azaspiro[2,4]heptane-5-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclobutyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(6-azaspiro[3.4]octane-6-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclobutyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-28-(2,2-dimethylazetidine-1-carbonyl)-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.09,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.4]octane-2-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(3-azabicyclo[3.2.0]heptane-3-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-methylazetidine-1-carbonyl)-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-3-cyclopentyl-37-cyclopropyl-9,24-diethyl-4,16,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9S,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-3-cyclopentyl-37-cyclopropyl-9-(2,2-difluoroethyl)-24-ethyl-4,16,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-27-(cyclopropylmethyl)-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46[Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propan-2-yl-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, and 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-6-(cyclopropylmethyl)-13,18,30-trimethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46A compound selected from the group consisting of [heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide or a salt thereof.

[159] A compound or salt thereof according to any one of [1] to

[158] that inhibits ALK.

[160] A pharmaceutical composition comprising a compound or salt thereof according to any one of [1] to

[158] .

[161] A pharmaceutical composition for inhibiting ALK in a subject, comprising a compound or salt thereof according to any one of [1] to

[158] .

[162] A pharmaceutical composition for treating and / or preventing cancer in a subject, comprising an effective amount of a compound or salt thereof according to any one of [1] to

[158] . [162-1] A pharmaceutical composition for treating and / or preventing cancer, comprising a compound or salt thereof according to any one of [1] to

[158] and used in combination with an ALK inhibitor. [162-2] A pharmaceutical composition for treating and / or preventing cancer, comprising an ALK inhibitor and used in combination with a compound or salt thereof according to any one of [1] to

[158] . [162-3] The pharmaceutical composition according to [162-1] or [162-2], wherein the ALK inhibitor is a compound selected from the group consisting of crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, ensartinib, repotrectinib, entrectinib, TPX-0131, and NVL-655 or a salt thereof.

[163] The pharmaceutical composition according to

[162] , wherein the cancer is a cancer having an ALK gene abnormality.

[164] The pharmaceutical composition according to

[162] , wherein the cancer is a lymphoma. [164-1] The pharmaceutical composition according to

[162] , wherein the cancer is an ALK fusion gene positive cancer. [164-2] The pharmaceutical composition according to any one of

[162] to [164-1], wherein the cancer is a cancer having an ALK-TKI resistance mutation.

[165] A pharmaceutical composition according to any one of

[161] to

[164] , wherein the subject is a human.

[166] A pharmaceutical composition according to any one of

[161] to

[165] , comprising a compound or a salt thereof according to any one of [1] to

[158] as an active ingredient.

[167] A compound or a salt thereof according to any one of [1] to

[158] for use in the treatment and / or prevention of cancer in a subject.

[168] A compound or a salt thereof according to

[167] , wherein the cancer is a cancer having an ALK gene abnormality.

[169] The cancer is,The compound or a salt thereof described in

[168] for lymphoma. [169-1] The compound or a salt thereof described in

[168] for cancer that is ALK fusion gene positive. [169-2] The compound or a salt thereof described in any of

[167] to [169-1] for cancer that has an ALK-TKI resistance mutation.

[170] The compound or a salt thereof described in any of [1] to

[158] for use in inhibiting ALK in a subject. [170-1] The compound or a salt thereof described in any of [1] to

[158] for use in combination with an ALK inhibitor in inhibiting ALK in a subject. [170-2] The compound or salt thereof according to [170-1], wherein the ALK inhibitor is a compound or salt thereof selected from the group consisting of crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, ensartinib, repotrectinib, entrectinib, TPX-0131, and NVL-655. [170-3] An ALK inhibitor for use in inhibition of ALK in a subject, used in combination with any compound or salt thereof according to [1] to

[158] . [170-4] The ALK inhibitor according to [170-3], wherein the ALK inhibitor is a compound or salt thereof selected from the group consisting of crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, ensartinib, repotrectinib, TPX-0131, and NVL-655.

[171] A compound or salt thereof described in any of

[167] to

[170] , wherein the subject is a human.

[172] Use of a compound or salt thereof described in any of [1] to

[158] in the manufacture of a medicament for treating and / or preventing cancer in a subject. [172-1] Use of a compound or salt thereof described in any of [1] to

[158] in combination with an ALK inhibitor in the manufacture of a medicament for treating and / or preventing cancer in a subject. [172-2] Use of an ALK inhibitor in combination with a compound or salt thereof described in any of [1] to

[158] in the manufacture of a medicament for treating and / or preventing cancer in a subject. [172-3] The ALK inhibitor is crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, ensartinib, repotrectinib, entrectinib, TPX-0131,Use according to [172-1] or [172-2], wherein the compound or a salt thereof is selected from the group consisting of and NVL-655.

[173] Use according to

[172] , wherein the cancer is a cancer having an ALK gene abnormality.

[174] Use according to

[173] , wherein the cancer is a lymphoma. [174-1] Use according to

[173] , wherein the cancer is an ALK fusion gene positive cancer. [174-2] Use according to any one of

[173] to [174-1], wherein the cancer is a cancer having an ALK-TKI resistance mutation.

[175] Use of any one of [1] to

[158] , wherein the compound or a salt thereof is in the manufacture of a pharmacopoeia for inhibiting ALK in a subject.

[176] Use according to any one of

[172] to

[175] , wherein the subject is a human. A method for treating and / or preventing cancer in a subject, comprising administering an effective amount of a compound or salt thereof described in any of [1] to

[158] to a subject in need thereof. A method for treating and / or preventing cancer in a subject, comprising administering a compound or salt thereof described in any of [1] to

[158] and an ALK inhibitor to the subject. The method according to [177-2], wherein the ALK inhibitor is a compound or salt thereof selected from the group consisting of crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, ensartinib, repotrectinib, entrectinib, TPX-0131, and NVL-655. The method according to [177-1], wherein the cancer is a cancer having an ALK gene abnormality. The method according to

[177] , wherein the cancer is a lymphoma. [179-1] The method according to

[177] , wherein the cancer is ALK fusion gene positive. [179-2] The method according to any one of

[177] to [179-1], wherein the cancer is ALK-TKI resistant mutation.

[180] A method for inhibiting ALK in a subject, comprising administering an effective amount of any one of [1] to

[158] or a salt thereof to a subject in need thereof.

[181] The method according to any one of

[177] to

[180] , wherein the subject is human.

[182] (2S)-2-(methylamino)-3-propane-2-yloxypropanoic acid, (2S)-4-cycloheptyl-2-(methylamino)butanoic acid,(2S)-2-(methylamino)-4-(1-methylcyclopropyl)butanoic acid, (2S,3S)-3-ethoxy-2-(methylamino)butanoic acid, (2S)-2-(4,4-difluorocyclohexyl)-2-(methylamino)acetic acid, (2S)-2-(methylamino)-2-(oxan-4-yl)acetic acid, (2S)-2-(3,3-difluorocyclobutyl)-2-(methylamino)acetic acid, (2S)-2-cycloheptyl-2-(methylamino)acetic acid, (2S)-2-(methylamino)-3-(2-methylpropoxy)propanoic acid, (2S)-3- Clopentyloxy-2-(methylamino)propanoic acid, (2S)-4-cyclopentyl-2-(methylamino)butanoic acid, (2S)-5,5-dimethyl-2-(methylamino)hexanoic acid, (2S)-4-(3-iodophenyl)-2-(methylamino)butanoic acid, (2S)-4-(2-methoxypyridine-3-yl)-2-(methylamino)butanoic acid, (2S)-4-(5-methoxypyridine-3-yl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-pyridine-2-ylbutanoic acid, (2S)-2-(methylamino)-4 -(4-methylpyridine-3-yl)butanoic acid, (2S)-4-(3,5-difluoropyridine-4-yl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-[3-(trifluoromethyl)pyridine-4-yl]butanoic acid, (2S)-4-(3-chloropyridine-4-yl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-(3-methylpyridine-4-yl)butanoic acid, (2S)-4-(3-fluoropyridine-4-yl)-2-(methylamino)butanoic acid, (2S)-2-cyclobutyl-2-(E (2S)-2-Cyclopropyl-2-(ethylamino)acetic acid, (2S)-2-(ethylamino)-3-(3-methylbutoxy)propanoic acid, (2S)-2-Cyclopropyl-2-(propylamino)acetic acid, (2R)-2-(propylamino)propanoic acid, (2S)-3-(3,3-difluorocyclobutyl)oxy-2-(methylamino)propanoic acid, (2S)-3-(4,4-difluorocyclohexyl)oxy-2-(methylamino)propanoic acid, (2S)-3-(cyclohexylmethoxy)-2-(methylamino)propanoic acid,(2S)-3-(2,2-dimethylpropoxy)-2-(methylamino)propanoic acid, (2S)-2-amino-3-[[(3R)-oxolan-3-yl]methoxy]propanoic acid, (2S)-2-amino-3-[[(3S)-oxolan-3-yl]methoxy]propanoic acid, (2S)-2-(methylamino)-4-(2-methylpyridine-3-yl)butanoic acid, (2S)-2-(methylamino)-4-(1-methyl-6-oxopyridine-3-yl)butanoic acid, (2S)-4-(2-fluorophenyl)-2-(methylamino)butanoic acid, (2S)-4-( 2-Methoxyphenyl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-[4-(trifluoromethyl)phenyl]butanoic acid, (2S)-4-(3-fluorophenyl)-2-(methylamino)butanoic acid, (2S)-4-(4-fluorophenyl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-(6-oxo-1H-pyridine-3-yl)butanoic acid, (2S)-2-amino-3-[2-[(1-methylcyclobutyl)amino]-2-oxoethoxy]propanoic acid, (2S)-2-amino-3-[2-[ (1-methylcyclopropyl)amino]-2-oxoethoxy]propanoic acid, (2S)-2-amino-3-[2-(cyclopentylamino)-2-oxoethoxy]propanoic acid, (2S)-2-amino-3-[2-(2-methylbutan-2-ylamino)-2-oxoethoxy]propanoic acid, (2S)-2-amino-3-[[(2R)-oxetan-2-yl]methoxy]propanoic acid, (2S)-2-amino-3-[[(2S)-oxetan-2-yl]methoxy]propanoic acid, (2S,3S)-3-cyclobutyloxy-2-(methylamino)butanoic acid, (2S,3S)-2-(methylamino)-3-propane-2-yloxybutanoic acid, (2S)-4-cyclohexylidene-2-(methylamino)butanoic acid, (3S)-3-amino-4-(3,3-difluoropyrrolidine-1-yl)-4-oxobutanoic acid, (3S)-3-amino-4-[cyclopropyl(methyl)amino]-4-oxobutanoic acid, (3S)-3-amino-4-(2-azaspiro[3,3]heptan-2-yl)-4-oxobutanoic acid, (3S)-3-amino-4-(3-ethyl-3-fluoroazetidine-1-yl)-4-oxobutanoic acid,Compounds selected from (3S)-3-amino-4-(3-fluoro-3-methylazetidine-1-yl)-4-oxobutanoic acid, (3S)-3-amino-4-(3-ethylazetidine-1-yl)-4-oxobutanoic acid, (3S)-3-amino-4-(3,3-dimethylazetidine-1-yl)-4-oxobutanoic acid, and (3S)-3-amino-4-(diethylamino)-4-oxobutanoic acid, or salts thereof, or compounds in which the amino group or carboxyl group thereof is protected by a protecting group.

[0007] In the above numbering, the numbers referenced by dependent terms include their sub-numbers unless otherwise specified. For example,

[12] referenced in a dependent term means

[12] , along with its sub-numbers [12-1], [12-2], [12-3], [12-4], and [12-5]. The same applies to other numbering.

[0008] According to the present invention, it is possible to provide a novel compound having ALK inhibitory activity.

[0009] Examples of abbreviations used in this specification, along with their meanings, are listed below: AA: Ammonium acetate Boc: tert-butoxycarbonyl DBU: 1,8-diazabicyclo[5.4.0]-7-undecene DCM: Dichloromethane DCE: 1,2-dichloroethane DEPBT: 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazine-4(3H)-one DIAD: Diisopropyl azodicarboxylic acid DIC: N,N'-diisopropylcarbodiimide DIPEA: N,N-diisopropylethylamine DMA: N,N-dimethylacetamide DMAP: N,N-dimethyl-4-aminopyridine DMF: N,N-dimethylformamide DMSO: Dimethyl sulfoxide dtbbpy: 4,4'-di-tert-butyl-2,2'-bipyridine EDCI・HCl: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride EDTA: ethylenediaminetetraacetic acid FA: formic acid Fmoc: 9-fluorenylmethyloxycarbonyl Fmoc-Cl: 9H-fluoren-9-ylmethyl chloroformate Fmoc-OSu: 9-fluorenylmethylN-succinimidyl carbonate HATU: O-(7-aza-1H-benzotriazole-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate HFIP: 1,1,1,3,3,3-hexafluoroisopropyl alcohol HOAt: 1-hydroxy-7-azabenzotriazole HOBt: 1-hydroxybenzotriazole HOOBt: 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine IPA: isopropyl alcohol NHPI: N-hydroxyphthalimide NMP: N-methyl-2-pyrrolidone Ns: o-nitrobenzenesulfonyl oxyma: cyano(hydroxyimino)ethyl acetate Pis: 2-phenylisopropyl PyAOP: (7-azabenzotriazole-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate PyOxim: [ethylcyano(hydroxyimino)acetate-O ２Tri-1-pyrrolidinylphosphonium hexafluorophosphate TBME: tert-butyl methyl ether TES: triethylsilane TFA: trifluoroacetic acid TFE: 2,2,2-trifluoroethanol THF: tetrahydrofuran THP: tetrahydropyranyl TIPS: triisopropylsilane TMSCl: chlorotrimethylsilane

[0010] The present invention will be described in detail below, including definitions of symbols and terms used herein, and embodiments of the present invention.

[0011] In this specification, the "~" indicating a numerical range includes the values ​​at both ends of the range; for example, "A~B" means a numerical range where A is greater than or equal to B and B is less than or equal to B.

[0012] In this specification, the term "approximately" when used in combination with a number means a range of values ​​within +10% and -10% of that number.

[0013] In this specification, the meaning of the term "and / or" includes any combination of "and" and "or" as appropriate. Specifically, for example, "A, B, and / or C" includes the following seven variations: (i) A, (ii) B, (iii) C, (iv) A and B, (v) A and C, (vi) B and C, (vii) A, B, and C.

[0014] In this specification, “one or more” means one or more numbers. When “one or more” is used in reference to the number of substituents on a group, it means a number from one up to the maximum number of substituents that the group may allow. Specifically, “one or more” may include, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and / or greater numbers.

[0015] In this specification, the names of each substituent may be described with the term "group." For example, "alkyl" may be called "alkyl group."

[0016] In this specification, "halogen" means fluorine, chlorine, bromine, or iodine. In the specification, F represents fluorine, Cl represents chlorine, Br represents bromine, and I represents iodine.

[0017] In this specification, "alkyl" refers to a linear or branched monovalent saturated hydrocarbon group derived by removing one arbitrary hydrogen atom from an aliphatic saturated hydrocarbon, which does not contain heteroatoms (atoms other than carbon and hydrogen atoms) or unsaturated carbon-carbon bonds in its skeleton, but has a hydrocarbyl or a subset of hydrocarbon group structures containing hydrogen and carbon atoms. Examples of alkyl groups include those having 1 to 20 carbon atoms (C １ ~C ２０ In the following specification, "C ｐ ~C ｑ " means an alkyl group with p to q carbon atoms, C １ ~C １５ Alkyl is preferred, C １ ~C １０ Alkyl is more preferred, C １ ~C ６ Alkyl is more preferred, C １ ~C ６ Alkyl is most preferred. Specific examples of alkyl groups include methyl, ethyl, n-propyl, i-propyl (1-methylethyl), n-butyl, s-butyl (1-methylpropyl), t-butyl, isobutyl (2-methylpropyl), n-pentyl, s-pentyl (1-methylbutyl), t-pentyl (1,1-dimethylpropyl), neopentyl (2,2-dimethylpropyl), isopentyl (3-methylbutyl), 3-pentyl (1-ethylpropyl), 1,2-dimethylpropyl, 2-methylbutyl, n-hexyl, n-heptyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1,1,2,2-tetramethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, and the like.

[0018] In this specification, "alkenyl" means one or more carbon-carbon double bonds (two adjacent sp２ It is a linear or branched monovalent unsaturated hydrocarbon group having carbon atom bonds. ２ Depending on the arrangement of the atoms or groups of atoms bonded to the carbon atom, the geometric form of the double bond can be entgegen (E) or tuzamen (Z), cis or trans configuration. Examples of alkenyls include C ２ ~C １０ It is an alkenyl, C ２ ~C ８ Alkenyl is preferred, C ２ ~C ７ Alkenyl is more preferred, C ２ ~C ６ Alkenyls are most preferred. Specific examples of alkenyls include ethenyl (vinyl), 1-propenyl, 2-propenyl (allyl, propa-2-enyl), isopropenyl, 1-butenyl, 2-butenyl (including cis and trans), 3-butenyl (buta-3-enyl), pentenyl, hexenyl, and the like.

[0019] In this specification, "alkynyl" refers to a linear or branched monovalent unsaturated hydrocarbon group having one or more carbon-carbon triple bonds (bonds formed by two adjacent sp carbon atoms). Examples of alkynyls include C ２ ~C １０ It is alkinyl, C ２ ~C ８ Alkinyl is preferred, C ２ ~C ７ Alkinyl is more preferred, C ２ ~C ６ Alkynnyl is most preferred. Specific examples of alkynyl include ethinyl, 1-propynyl, propargyl(2-propynyl), 1-butynyl, 2-butynyl, 3-butynyl(buta-3-inyl), pentynyl, hexynyl, and the like.

[0020] In this specification, "haloalkyl" refers to a group in which one or more hydrogen atoms of an "alkyl" group are substituted with a "halogen". Preferred haloalkyls are, for example, groups in which one to six hydrogen atoms of the alkyl group that are permitted to be substituted are substituted with halogens. Examples of haloalkyls include haloC １ ~C２０ It is alkyl, and halo C １ ~C １０ Alkyl is preferred, Halo C １ ~C ８ Alkyl is more preferred, halo C １ ~C ６ Alkyl is most preferred. Halo C １ ~C ６ Examples of alkyl groups include groups in which one to six hydrogen atoms of the alkyl group that are permitted to be substituted are replaced with fluorine atoms, preferably groups in which one to five hydrogen atoms are replaced with fluorine atoms, more preferably groups in which one to four hydrogen atoms are replaced with fluorine atoms, and most preferably groups in which one to three hydrogen atoms are replaced with fluorine atoms. Specific examples of haloalkyl groups include difluoromethyl, trifluoromethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 3,3-difluoropropyl, 3,3,3-trifluoropropyl, 4,4-difluorobutyl, 4,4,4-trifluorobutyl, and 5,5-difluoropentyl.

[0021] In this specification, "cycloalkyl" refers to a saturated or partially saturated cyclic monovalent non-aromatic hydrocarbon ring group (alicyclic ring group). The carbon atoms constituting the ring may be oxidized to include carbonyl atoms. Cycloalkyls may be selected from the group consisting of monocycles, fused rings, and spirocycles. In this specification, cycloalkyls containing a monocycle are referred to as monocyclic cycloalkyls, i.e., monocyclic alicyclic ring groups. Cycloalkyls containing a fused ring are referred to as fused cycloalkyls, i.e., fused alicyclic ring groups. Cycloalkyls containing a spirocycle are referred to as spirocyclic cycloalkyls, i.e., spirocyclic alicyclic ring groups. Cycloalkyls may form fused rings with saturated alicyclic rings such as cyclopentane rings or cyclohexane rings, unsaturated alicyclic rings such as cyclopentene rings or cyclohexene rings, or aromatic hydrocarbon rings such as benzene rings or naphthalene rings. Cycloalkyls may form spiro rings with saturated alicyclic rings such as cyclopropane rings, cyclobutane rings, cyclopentane rings, and cyclohexane rings. Examples of cycloalkyls include C ３ ~C １０ It is a cycloalkyl, C３ ~C ８ Cycloalkyl is preferred, C ３ ~C ７ Cycloalkyl is more preferred, C ３ ~C ６ Cycloalkyls are most preferred. Specific examples of cycloalkyls include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, spiro[3.3]heptyl, and cyclohexenyl.

[0022] In this specification, "cycloalkylalkyl" refers to a group in which one or more hydrogen atoms of "alkyl" are substituted with "cycloalkyl". A preferred cycloalkylalkyl is, for example, a group in which one hydrogen atom of alkyl is substituted with cycloalkyl. A preferred cycloalkylalkyl is, for example, C ３ ~C １０ Cycloalkyl C １ ~C ２０ It is alkyl, C ３ ~C １０ Cycloalkyl C １ ~C ６ Alkyl is preferred, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl is more preferred, C ３ ~C ６ Cycloalkyl C １ ~C ２ Alkyl is most preferred. Specific examples of cycloalkylalkyls include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-cyclopropylethyl, 2-(cyclopentyl)ethyl, 2-cyclohexylethyl, 2-cyclohexylpropyl, and 2-(1-methylcyclopropyl)ethyl.

[0023] In this specification, "cycloalkylidene alkyl" refers to a group in which a cycloalkylidene is bonded to the site where two hydrogen atoms bonded to the same carbon atom of the "alkyl" group have been removed. Examples of cycloalkylidene alkyls include C ３ ~C １０Cycloalkylidene C １ ~C ２０ It is alkyl, C ３ ~C １０ Cycloalkylidene C １ ~C ６ Alkyl is preferred, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl is more preferred, C ３ ~C ６ Cycloalkylidene C １ ~C ２ Alkyl is most preferred. Specific examples of cycloalkylidene alkyl include cyclopropylidene methyl, cyclobutylidene methyl, cyclopentylidene methyl, cyclohexylidene methyl, 2-(cyclohexylidene)ethyl, and 3-cyclohexylidenepropyl.

[0024] In this specification, "aminocarbonyl" refers to a group in which "amino" is bonded to a carbonyl carbon atom. It is sometimes also called an amide. Examples of aminocarbonyls include -CONH ２ Mono C １ ~C ６ Alkylaminocarbonyl, diC １ ~C ６ Alkylaminocarbonyl, monoC ３ ~C ８ Examples include cycloalkylaminocarbonyls and 3- to 10-membered cyclic aminocarbonyls. Specifically, as aminocarbonyls, -CONH ２N-methylaminocarbonyl, N-ethylaminocarbonyl, N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl, methoxy(methyl)aminocarbonyl, N-cyclopropylaminocarbonyl, N-cyclobutylaminocarbonyl, N-cyclopentylaminocarbonyl, N-cyclohexylaminocarbonyl, (azetidine-1-yl)carbonyl, (pyrrolidine-1-yl)carbonyl, (piperidine-1-yl)carbonyl, (piperazine-1-yl)carbonyl Carbonyl, (morpholine-4-yl)carbonyl, (oxazolidine-3-yl)carbonyl, (3,3-dimethylpyrrolidine-1-yl)carbonyl, (3,3-difluoropyrrolidine-1-yl)carbonyl, (2-azaspiro[3.3]heptan-2-yl)carbonyl, (2-oxa-6-azaspiro[3.3]heptan-6-yl)carbonyl, [(2R)-2-methylpyrrolidine-1-yl]carbonyl, (7-azabicyclo[2.2.1]heptan-7-yl)carbonyl , (3-ethylazetidine-1-yl)carbonyl, (3-azabicyclo[3.1.0]hexane-3-yl)carbonyl, (N-cyclopropyl-N-methylamino)carbonyl, (3-methylazetidine-1-yl)carbonyl, (3,3-difluoroazetidine-1-yl)carbonyl, (5-azaspiro[2.3]hexane-5-yl)carbonyl, (5-azaspiro[2.4]heptan-5-yl)carbonyl, (6-azaspiro[3.4]octane-6-yl)carbonyl, (3,3-dimethylazetidine-1-yl)carbonyl, (3-fluoro-3-methylazetidine-1-yl)carbonyl, (3-ethyl-3-fluoroazetidine-1-yl)carbonyl, (3-isopropylazetidine-1-yl)carbonyl, (2-azaspiro[3.4]octan-2-yl)carbonyl, (3-propylazetidine-1-yl)carbonyl, (6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)carbonyl, (3-azabicyclo[3.2.[0]Heptan-3-yl)carbonyl, (3-fluoro-3-propyl-azetidine-1-yl)carbonyl, (3-fluoroazetidine-1-yl)carbonyl, (3-methoxy-3-methylazetidine-1-yl)carbonyl, (3-ethyl-3-methylazetidine-1-yl)carbonyl, [(3R)-3-fluoro-3-methylpyrrolidine-1-yl]carbonyl, [(3R)-3-methylpyrrolidine-1-yl]carbonyl Examples include carbonyl, [(3S)-3-methylpyrrolidine-1-yl]carbonyl, (3-methoxyazetidine-1-yl)carbonyl, (2,2-dimethylazetidine-1-yl)carbonyl, (6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-yl)carbonyl, (6,6-difluoro-3-azabicyclo[3.1.0]hexane-3-yl)carbonyl, and N-methyl-N-propyl-aminocarbonyl.

[0025] In this specification, "alkoxy" refers to a group in which an alkyl group is bonded to an oxygen atom (-OR (where R is alkyl)). Examples of alkoxy groups include C １ ~C ２０ It is an alkoxy, C １ ~C １０ Alkoxy is preferred, C １ ~C ８ Alkoxy is more preferred, C １ ~C ６ Alkoxy is most preferred. Specific examples of alkoxy include methoxy, ethoxy, 1-propoxy, 2-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, pentyloxy, and 3-methylbutoxy.

[0026] In this specification, "haloalkoxy" refers to a group in which one or more hydrogen atoms of an "alkoxy" are substituted with a "halogen". Preferred haloalkoxys are, for example, groups in which one to six hydrogen atoms of the alkoxy that are permitted to be substituted are substituted with halogens. For example, halo C １ ~C ２０ It is an alkoxy and halo C １ ~C １０ Alkoxy is preferred, and halo C １ ~C８ Alkoxy is more preferable, halo C １ ~C ６ Alkoxy is most preferred. Halo C １ ~C ６ Examples of alkoxy groups include those in which 1 to 6 hydrogen atoms of the alkoxy that are permitted to be substituted are replaced with fluorine atoms, with a preference for groups in which 1 to 5 hydrogen atoms are replaced with fluorine atoms, a preference for groups in which 1 to 4 hydrogen atoms are replaced with fluorine atoms, and a preference for groups in which 1 to 3 hydrogen atoms are replaced with fluorine atoms. Specific examples of haloalkoxys include difluoromethoxy, trifluoromethoxy, 2,2-difluoroethoxy, 2,2,2-trifluoroethoxy, 3-fluoropropoxy, 3,3-difluoropropoxy, 2,2-difluoropropoxy, 4,4-difluorobutoxy, and 5,5-difluoropentoxy.

[0027] In this specification, "cycloalkoxy" refers to a group in which a "cycloalkyl" is bonded to an oxygen atom (-OR (where R is cycloalkyl)). Examples of cycloalkoxys include C ３ ~C １０ It is a cycloalkoxy, C ３ ~C ８ Cycloalkoxy is preferred, C ３ ~C ７ Cycloalkoxy is more preferred, C ３ ~C ６ Cycloalkoxy is most preferred. Examples of cycloalkoxy include cyclopropoxy, cyclobutoxy, cyclopentoxy, cyclohexoxy, and cycloheptoxy.

[0028] In this specification, "alkoxyalkyl" refers to a group in which one or more hydrogen atoms of "alkyl" are substituted via the oxygen atoms of "alkoxy". Preferred alkoxyalkyls are, for example, groups in which one hydrogen atom of alkyl is substituted with alkoxy. Examples of alkoxyalkyls include C １ ~C ６ Alkoxy C １ ~C ２０ It is alkyl, C １ ~C６ Alkoxy C １ ~C １５ Alkyl is preferred, C １ ~C ６ Alkoxy C １ ~C １０ Alkyl is more preferred, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl is most preferred. Examples of alkoxyalkyls include methoxymethyl, ethoxymethyl, 1-propoxymethyl ((n-propoxy)methyl), 2-propoxymethyl ((propan-2-yloxy)methyl), n-butoxymethyl, i-butoxymethyl, s-butoxymethyl, t-butoxymethyl, pentoxymethyl, 3-methylbutoxymethyl ((3-methylbutoxy)methyl), 1-methoxyethyl, 2-methoxyethyl, 1-ethoxyethyl, 2-ethoxyethyl, (2,2-dimethylpropoxy)methyl, 1-(n-propoxy)ethyl, 1-isopropyloxyethyl, and the like.

[0029] In this specification, "cycloalkoxyalkyl" refers to a group in which one or more hydrogen atoms of an "alkyl" group are substituted with "cycloalkoxy". A preferred cycloalkoxyalkyl group is, for example, a group in which one hydrogen atom of an alkyl group is substituted with cycloalkoxy. A preferred cycloalkoxyalkyl group is, for example, C ３ ~C １０ Cycloalkoxy C １ ~C ６ It is alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl is preferred, C ３ ~C ７ Cycloalkoxy C １ ~C ６ Alkyl is more preferred, C ３ ~C ６ Cycloalkoxy C １ ~C ６Alkyl is most preferred. Examples of cycloalkoxyalkyls include cyclopropoxymethyl, cyclobutoxymethyl, cyclopentoxymethyl, (cycloheptyloxy)methyl, (cyclohexyloxy)methyl, (cycloheptoxy)methyl, (cyclohexoxy)methyl, 1-cyclohexyloxyethyl, (cyclohexoxy)ethyl, and 1-cyclobutoxyethyl.

[0030] In this specification, "cycloalkylalkoxy" refers to a group in which the alkyl moiety of "cycloalkylalkyl" is bonded to an oxygen atom (-O-R-Cy (R is alkylene, Cy is cycloalkyl)). Examples of cycloalkylalkoxy include C ３ ~C １０ Cycloalkyl C １ ~C ６ It is an alkoxy, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkoxy is preferred, C ３ ~C ７ Cycloalkyl C １ ~C ６ Alkoxy is more preferred, C ３ ~C ６ Cycloalkyl C １ -C ６ Alkoxy is most preferred. Specific examples of cycloalkylalkoxy include cyclopropyl methoxy, cyclobutyl methoxy, cyclopentyl methoxy, and cyclohexyl methoxy.

[0031] In this specification, "cycloalkylalkoxyalkyl" refers to a group in which one or more hydrogen atoms of "alkyl" are substituted via the oxygen atoms of "cycloalkylalkoxy". A preferred cycloalkylalkoxyalkyl group is, for example, a group in which one hydrogen atom of alkyl is substituted with a cycloalkylalkoxyalkyl group. A preferred cycloalkylalkoxyalkyl group is, for example, C ３ ~C １０ Cycloalkyl C １ ~C ６ Alkoxy C １ ~C １０It is alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl is preferred, C ３ ~C ７ Cycloalkyl C １ ~C ４ Alkoxy C １ ~C ４ Alkyl is more preferred, C ３ ~C ６ Cycloalkyl C １ ~C ３ Alkoxy C １ ~C ３ Alkyl is most preferred. Specific examples of cycloalkylalkoxyalkyls include cyclopropyl methoxymethyl, cyclobutyl methoxymethyl, 2-(cyclopentyl methoxy)ethyl, cyclohexyl methoxymethyl, (2-cyclopropyl ethoxy)methyl, (2-cyclobutyl ethoxy)methyl, (2-cyclohexyl ethoxy)methyl, and (cyclopropyl methoxy)methyl.

[0032] In this specification, "amino" means -NRR', where N represents a nitrogen atom, and R and R' are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl, or R and R' together with the nitrogen atom to which they are bonded to form a ring. Examples of aminos include -NH ２ Mono C １ ~C ６ Alkylamino, diC １ ~C ６ Examples include alkylaminos and 4- to 8-membered cyclic aminos.

[0033] In this specification, "monoalkylamino" refers to a group in "amino (-NRR')" where R is hydrogen and R' is alkyl. Examples of monoalkylaminos include monoC １ ~C ２０ It is an alkylamino, mono-C １ ~C １５Alkylaminos are preferred, monoC １ ~C １０ Alkylaminos are more preferred, monoC １ ~C ６ Alkylaminos are most preferred. Specific examples of monoalkylaminos include methylamino, ethylamino, n-propylamino, i-propylamino, n-butylamino, s-butylamino, and t-butylamino.

[0034] In this specification, "dialkylamino" refers to a group in which R and R' of "amino (-NRR')" are independently "alkyl" groups. Examples of dialkylaminos include diC １ ~C ２０ It is an alkylamino, diC １ ~C １５ Alkylaminos are preferred, diC １ ~C １０ Alkylaminos are more preferred, diC １ ~C ６ Alkylaminos are most preferred. Specific examples of dialkylaminos include dimethylamino, diethylamino, and methylethylamino.

[0035] In this specification, "monocycloalkylamino" refers to a group in "amino (-NRR')" where R is hydrogen and R' is "cycloalkyl". Examples of monocycloalkylaminos include monoC ３ ~C １０ It is a cycloalkylamino, mono C ３ ~C ８ Cycloalkylaminos are preferred, monoC ３ ~C ７ Cycloalkylaminos are more preferred, monoC ３ ~C ６ Cycloalkylaminos are most preferred. Specific examples of cycloalkyls include cyclopropylamino, cyclobutylamino, cyclopentylamino, and cyclohexylamino.

[0036] In this specification, "cyclic amino" refers to a group in which the R and R' of "amino(-NRR')" form a ring together with the nitrogen atom to which they are bonded. Cyclic aminos may be selected from the group consisting of monocyclic, fused, and spirocyclic rings. In this specification, cyclic aminos containing monocyclic rings are referred to as monocyclic cyclic aminos. Examples of cyclic aminos include 3- to 14-membered cyclic aminos, with 3- to 12-membered cyclic aminos being preferred, 3- to 10-membered cyclic aminos being more preferred, and 4- to 7-membered cyclic aminos being most preferred. Specific examples of cyclic aminos include 1-azetidyl, 1-pyrrolidyl, 1-piperidyl, 1-piperazyl, 4-morpholinyl, 3-oxazolidyl, 1,1-dioxidedothiomorpholinyl-4-yl, and 3-oxa-8-azabicyclo[3.2.1]octan-8-yl.

[0037] In this specification, "aryl" refers to a monovalent aromatic hydrocarbon ring group consisting of a monocyclic or fused ring exhibiting monovalent aromaticity. In this specification, aryls consisting of a monocyclic ring are referred to as monocyclic aryls, and aryls consisting of a fused ring are referred to as fused-ring aryls. Examples of aryls include C ６ ~C １４ It is aryl, C ６ Ariel, C １０ Aryl and C １４ Aryl is preferred, C ６ Aryl and C １０ Aryl is more preferred, C ６ Aryls are most preferred. Specific examples of aryls include phenyl, 1-naphthyl, and 2-naphthyl. These aryls may also have substituents, such as tolyl, xylyl, and 2,4-dinitrophenyl.

[0038] In this specification, "aralkyl (arylalkyl)" refers to a group in which one or more hydrogen atoms of an "alkyl" group are substituted with an "aryl" group. Examples of aralkyls include C ７ ~C ２０ It is Aralkir, C ７ ~C １８ Aralkyl is preferred, C ７ ~C １６ Aralkir is more preferred, C７ ~C １４ Aralquil is the most preferable. C ７ ~C ２０ For example, C ６ ~C １０ Aryl C １ ~C １０ It is alkyl, C ６ ~C １０ Aryl C １ ~C ８ Alkyl is preferred, C ６ Aryl C １ ~C ８ Alkyl or C １０ Aryl C １ ~C ８ Alkyl is more preferred, C ６ Aryl C １ ~C ８ Alkyl is most preferred. ７ ~C １８ For example, C ６ ~C １０ Aryl C １ ~C ８ It is alkyl, C ６ ~C １０ Aryl C １ ~C ６ Alkyl is preferred, C ６ Aryl C １ ~C ６ Alkyl or C １０ Aryl C １ ~C ６ Alkyl is more preferred, C ６ Aryl C １ ~C ６ Alkyl is most preferred. ７ ~C １６ For example, C ６ ~C １０ Aryl C １ ~C ６ It is alkyl, C ６ ~C １０ Aryl C １ ~C ４ Alkyl is preferred, C ６ Aryl C １ ~C ４ Alkyl or C １０Aryl C １ ~C ４ Alkyl is more preferred, C ６ Aryl C １ ~C ４ Alkyl is most preferred. ７ ~C １４ For example, C ６ ~C １０ Aryl C １ ~C ４ It is alkyl, C ６ ~C １０ Aryl C １ ~C ３ Alkyl is preferred, C ６ Aryl C １ ~C ３ Alkyl or C １０ Aryl C １ ~C ３ Alkyl is more preferred, C ６ Aryl C １ ~C ３ Alkyl is most preferred. Specific examples of aralkyls include benzyl, 2-phenylethyl, 3-phenylpropyl, and 2-(1-naphthyl)ethyl.

[0039] In this specification, "aryloxy" refers to a group in which "aryl" is bonded to an oxygen atom (-OAr (Ar is aryl)). Examples of aryloxys include C ６ ~C １４ It is an aryloxy, C ６ Aryloxy, C １０ Aryloxy and C １４ Aryl oxy is preferred, C ６ Aryloxy and C １０ Aryloxy is more preferred, C ６ Aryloxys are most preferred. Specific examples of aryloxys include phenyloxy, 1-naphthyloxy, and 2-naphthyloxy. These aryloxys may also have substituents, such as tolyloxy, xylyloxy, and 2,4-dinitrophenyloxy.

[0040] In this specification, "aryloxyalkyl" refers to a group in which one or more hydrogen atoms of "alkyl" are substituted with "aryloxy". Preferred aryloxyalkyl groups include, for example, a group in which one hydrogen atom of alkyl is substituted with aryloxy. Examples of aryloxyalkyl groups include C ６ ~C １４ Aryloxy C １ ~C ６ It is alkyl, C ６ Aryloxy C １ ~C ６ Alkyl, C １０ Aryloxy C １ ~C ６ Alkyl and C １４ Aryloxy C １ ~C ６ Alkyl is preferred, C ６ Aryloxy C １ ~C ６ Alkyl and C １０ Aryloxy C １ ~C ６ Alkyl is more preferred, C ６ Aryloxy C １ ~C ６ Alkyl is most preferred. Specific examples of aryloxyalkyls include phenyloxymethyl (phenoxy)methyl, 1-naphthyloxymethyl, and 2-phenyloxyethyl (2-phenoxyethyl).

[0041] In this specification, "heteroaryl" refers to a monovalent aromatic heterocyclic group comprising a monocyclic or fused ring that contains at least one heteroatom in addition to a carbon atom and exhibits aromaticity. In this specification, a heteroaryl composed of a monocyclic ring is referred to as a monocyclic heteroaryl, and a heteroaryl composed of a fused ring is referred to as a fused-ring heteroaryl. The number of atoms constituting the ring of the heteroaryl is, for example, 5 to 14 (5 to 14-membered heteroaryl), preferably 5 to 13 (5 to 13-membered heteroaryl), more preferably 5 to 10 (5 to 10-membered heteroaryl), and most preferably 5 to 7 (5 to 7-membered heteroaryl). Examples of heteroaryl compounds include five-membered heteroaryls such as furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, oxazolyl, triazolyl, and tetrazolyl; six-membered heteroaryls such as pyridyl, pyrimidyl, pyridadinyl, pyrazinyl, and triazinyl; nine-membered heteroaryls such as benzofuranil, benzothienyl, benzothiazolyl, benzimidazolyl, benzotriazolyl, indolyl, indazolyl, and pyrazolopyridyl; and ten-membered heteroaryls such as quinolyl, isoquinolyl, sinnolinyl, quinazolinyl, and quinoxalinyl.

[0042] In this specification, "heteroarylalkyl" refers to a group in which one or more hydrogen atoms of an "alkyl" group are substituted with a "heteroaryl" group. A preferred heteroarylalkyl group is, for example, a group in which one hydrogen atom of an alkyl group is substituted with a heteroaryl group. An example of a heteroarylalkyl group is a 5-10 membered heteroaryl C group. １ ~C ６ Alkyl, 5-10 membered heteroaryl C １ ~C ４ Alkyl is preferred, and 5-10 membered heteroaryl C １ ~C ３ Alkyl is more preferred, and 5-10 membered heteroaryl C １ ~C ２Alkyl is most preferred. Examples of heteroarylalkyls include 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-furanylmethyl, 2-thienylmethyl, 3-thienylmethyl, 4-thiazolylmethyl, 2-(pyridin-3-yl)ethyl, 2-(pyridin-4-yl)ethyl, 2-(6-oxo-1H-pyridin-3-yl)ethyl, 2-(1-methyl-6-oxo-3-pyridyl)ethyl, 2-(1,3-benzoxazole-6-yl)ethyl, 2-(imidazo[1,2-a]pyridin-6-yl)ethyl, 2-(2-methylindazole-5-yl)ethyl, and 2-(2-pyridyl)ethyl.

[0043] In this specification, "heterocyclyl" refers to a heterocyclic group that, in addition to carbon atoms, contains, preferably, 1 to 5, more preferably 1 to 3, heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms, and sulfur atoms, and may have double and / or triple bonds in the ring. The carbon atoms in the ring of the heterocyclyl may be oxidized to form carbonyls. In this specification, a heterocyclyl containing a monocyclic ring is referred to as a monocyclic heterocyclyl, a heterocyclyl containing a fused ring is referred to as a fused-ring heterocyclyl, and a heterocyclyl containing a spirocyclic ring is referred to as a spirocyclic heterocyclyl. A heterocyclyl may form a fused ring with, for example, a saturated alicyclic ring such as a cyclopentane ring or a cyclohexane ring, an unsaturated alicyclic ring such as a cyclohexene ring, a saturated heterocyclic ring such as a tetrahydropyran ring, a dioxane ring, or a pyrrolidine ring, an aromatic hydrocarbon ring such as a benzene ring or a naphthalene ring, or a pyridine ring, pyrimidine ring, or pyrazine ring. For example, a heterocyclil may form a spiro ring with a saturated alicyclic ring such as a cyclopentane ring or a cyclohexane ring, or with a saturated heterocycle such as a tetrahydropyran ring, a dioxane ring, or a pyrrolidine ring. The number of atoms constituting the heterocyclil ring is, for example, 3 to 14 (3 to 14-membered heterocyclil), preferably 3 to 12 (3 to 12-membered heterocyclil), more preferably 3 to 10 (3 to 10-membered heterocyclil), and most preferably 4 to 7 (4 to 7-membered heterocyclil). Examples of heterocyclyls include azetidinyl, oxylanil, oxetanil, thietanil, tetrahydrofuranil, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, oxazolidinyl, isoxazolidinyl, thiazolidinyl, isothiazolidinyl, thiadiazolidinyl, oxoxazolidinyl, dioxolanil, tetrahydropyranil, morpholinil, thiomorpholinil, 4-oxopyrrolidinyl, piperidinyl, 4-oxopiperidinyl, piperazinyl, dioxanil, oxan-4-yl, or rings in which one or more single bonds in these saturated heterocycles are replaced by double or triple bonds.

[0044] In this specification, "heterocyclylalkyl" refers to a group in which one or more hydrogen atoms of an "alkyl" group are substituted with a "heterocyclyl". Preferred heterocyclylalkyl groups include, for example, groups in which one hydrogen atom of an alkyl group is substituted with a heterocyclyl. Examples of heterocyclylalkyl groups include 3-14 membered heterocyclyl C １ ~C ６ Alkyl, 3-12 membered heterocyclyl C １ ~C ６ Alkyl is preferred, and 3-10 membered heterocyclyl C １ ~C ４ Alkyl is more preferred, and 4-7 membered heterocyclyl C １ ~C ３ Alkyl is most preferred. Examples of heterocyclylalkyls include azetidine-1-ylmethyl, azetidine-3-ylmethyl, oxetane-3-ylmethyl, 2-(tetrahydrofuran-3-yl)ethyl, (1-methylpyrrolidine-3-yl)methyl, 2-morpholinoethyl, 3-(1-piperidinyl)propyl, 3-(4-methylpiperazine-1-yl)propyl, and 2-(4-tetrahydropyran-4-yl)ethyl.

[0045] In this specification, "alkylene" refers to a divalent saturated hydrocarbon group derived by removing two hydrogen atoms bonded to different carbon atoms of an aliphatic saturated hydrocarbon. Examples of alkylenes include C １ ~C ２０ It is alkylene, C １ ~C １５ Alkylene is preferred, C １ ~C １０ Alkylene is more preferred, C １ ~C ６ Alkylenes are most preferred. Specifically, methylene (-CH4) is preferred as an alkylene. ２ -), ethylene (-(CH ２ ) ２ -), n-propylene (-(CH ２ ) ３ -), i-propylene (-CH(CH ３ )CH ２ -), n-butylene (-(CH ２ )４ -), s-butylene (-CH(CH ３ )CH ２ CH ２ -), n-pentylene (-(CH ２ ) ５ -), n-hexylene (-(CH ２ ) ６ Examples include -).

[0046] In this specification, "alkenylene" refers to a divalent group derived by removing one arbitrary hydrogen atom from the aforementioned "alkenyl." ２ Depending on the arrangement of the atoms or groups of atoms bonded to the carbon atom, the geometric form of the double bond can be entgegen (E) or tuzamen (Z), cis or trans configuration. Examples of alkenylenes include C ２ ~C １０ It is an alkenylene, C ２ ~C ８ Alkenylene is preferred, C ２ ~C ７ Alkenylene is more preferred, C ２ ~C ６ Alkenylenes are most preferred. Specific examples of alkenylenes include etenylene (vinylene), 1-propenylene, 2-propenylene (alylene), isopropenylene, 1-butenylene, 2-butenylene (including cis and trans forms), 3-butenylene, pentenylene, hexenylene, and the like.

[0047] In this specification, "substituents containing an oxygen atom" means hydroxy(-OH), oxy(-OR), oxo(=O), carbonyl(-C(=O)-R), carboxyl(-CO) ２ H), oxycarbonyl (-C(=O)-OR), carbonyloxy (-O-C(=O)-R), sulfanylcarbonyl (-C(=O)-SR), carbonylsulfanyl (-S-C(=O)-R), aminocarbonyl (-C(=O)-NRR'), carbonylamino (-NH-C(=O)-R), oxycarbonylamino (-NH-C(=O)-OR), thiocarboxyl (-C(=O)-SH), carboxylcarbonyl (-C(=O)-CO ２Examples include H). Examples of oxy(-OR) include alkoxy, haloalkoxy, cycloalkoxy, aralkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkylalkoxy, heterocyclylalkoxy, alkoxyalkoxy, alkylaminoalkoxy, aryloxy, heteroaryloxy, heterocyclyloxy, alkenyloxy, etc. Examples of carbonyl(-C(=O)-R) include formyl(-C(=O)-H), alkylcarbonyl, cycloalkylcarbonyl, cycloalkylalkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, arylcarbonyl, heteroarylcarbonyl, aralkylcarbonyl, etc. Examples of oxycarbonyl(-C(=O)-OR) include alkyloxycarbonyl, cycloalkyloxycarbonyl, cycloalkylalkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, aralkyloxycarbonyl, etc. Examples of carbonyloxy (-O-C(=O)-R) include alkylcarbonyloxy, haloalkylcarbonyloxy, cycloalkylcarbonyloxy, cycloalkylalkylcarbonyloxy, alkenylcarbonyloxy, alkynylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, and aralkylcarbonyloxy. Examples of sulfanylcarbonyl (-C(=O)-SR) include alkylsulfanylcarbonyl, cycloalkylsulfanylcarbonyl, cycloalkylalkylsulfanylcarbonyl, alkenylsulfanylcarbonyl, alkynylsulfanylcarbonyl, arylsulfanylcarbonyl, heteroarylsulfanylcarbonyl, and aralkylsulfanylcarbonyl.Examples of carbonyl sulfanyl (-S-C(=O)-R) include alkylcarbonyl sulfanyl, cycloalkylcarbonyl sulfanyl, cycloalkylalkylcarbonyl sulfanyl, alkenylcarbonyl sulfanyl, alkynylcarbonyl sulfanyl, arylcarbonyl sulfanyl, heteroarylcarbonyl sulfanyl, and aralkylcarbonyl sulfanyl. Examples of aminocarbonyl (-C(=O)-NR(R')) include alkylaminocarbonyl, cycloalkylaminocarbonyl, cycloalkylalkylaminocarbonyl, alkenylaminocarbonyl, alkynylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, and aralkylaminocarbonyl. Examples of carbonylamino acids (-NH-C(=O)-R) include alkylcarbonylamino acids, cycloalkylcarbonylamino acids, cycloalkylalkylcarbonylamino acids, alkenylcarbonylamino acids, alkynylcarbonylamino acids, arylcarbonylamino acids, heteroarylcarbonylamino acids, and aralkylcarbonylamino acids. Examples of oxycarbonylamino acids (-NH-C(=O)-OR) include alkyloxycarbonylamino acids, cycloalkyloxycarbonylamino acids, cycloalkylalkyloxycarbonylamino acids, alkenyloxycarbonylamino acids, alkynyloxycarbonylamino acids, aryloxycarbonylamino acids, heteroaryloxycarbonylamino acids, and aralkyloxycarbonylamino acids.

[0048] In this specification, "substituent containing a nitrogen atom" means azide (-N ３ Also called "azide group"), cyano(-CN), primary amino(-NH) ２ ), secondary amino(-NH-R), tertiary amino(-NR(R')), amidino(-C(=NH)-NH ２ ), substitution amidino (-C (=NR)-NR' (R'')), guanidino (-NH-C (=NH)-NH ２Examples include substituted guanidinos (-NR-C (=NR'')-NR'(R'')), aminocarbonylaminos (-NR-CO-NR'(R'')), etc. Examples of secondary aminos (-NH-R) include alkylaminos, cycloalkylaminos, cycloalkylalkylaminos, alkenylaminos, alkynylaminos, arylaminos, heteroarylaminos, and aralkylaminos. Examples of tertiary aminos (-NR(R')) include tertiary aminos in which R and R' are independently selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and aralkyl. Examples include dialkylaminos, alkyl(cycloalkyl)aminos, alkyl(cycloalkylalkyl)aminos, dialkenylaminos, dialkynylaminos, diarylaminos, alkyl(heteroaryl)aminos, and dialkylaminos. Any two substituents (R and R') above may form a ring including the nitrogen atom to which they are bonded. Examples of substituted amidinos (-C(=NR)-NR'(R'')) include substituted amidinos in which the three substituents R, R', and R'' on the nitrogen atom are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and aralkyl, or groups in which these groups form a ring. Examples of substituted guanidinos (-NR-C(=NR''')-NR'(R'')) include substituted guanidinos in which R, R', R'', and R''' are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and aralkyl, or groups in which these groups form a ring. Examples of aminocarbonylaminos (-NR-CO-NR'(R'')) include aminocarbonylaminos in which R, R', and R'' are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and aralkyl, or groups in which these groups form a ring.

[0049] In this specification, "substituents containing a sulfur atom" means thiol (-SH), sulfanyl (-S-R), sulfinyl (-S=O-R), sulfonyl (-S(O) ２ -R), sulfo(-SO ３ H), pentafluorosulfanil (-SF ５ ), disulfanyl (-S-S-R), sulfonylamino (-NH-SO ２ -R), aminosulfonyl (-SO ２ -NR(R')), sulfamoylamino(-NH-SO) ２ Examples include -NR(R')). Examples of sulfanyl (-SR) include alkylsulfanyl, haloalkylsulfanyl, cycloalkylsulfanyl, aralkylsulfanyl, heteroarylalkylsulfanyl, heterocyclylalkylsulfanyl, cycloalkylalkylsulfanyl, heterocyclylalkylsulfanyl, alkoxyalkylsulfanyl, alkylaminoalkylsulfanyl, arylsulfanyl, heteroarylsulfanyl, heterocyclylsulfanyl, alkenylsulfanyl, etc. Examples of sulfinyl (-S=O-R) include alkylsulfinyl, haloalkylsulfinyl, cycloalkylsulfinyl, aralkylsulfinyl, heteroarylalkylsulfinyl, heterocyclylalkylsulfinyl, cycloalkylalkylsulfinyl, heterocyclylalkylsulfinyl, alkoxyalkylsulfinyl, alkylaminoalkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, heterocyclylsulfinyl, alkenylsulfinyl, etc. Sulfonyl (-S(O) ２Examples of -R include alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, aralkylsulfonyl, heteroarylalkylsulfonyl, heterocyclylalkylsulfonyl, cycloalkylalkylsulfonyl, heterocyclylalkylsulfonyl, alkoxyalkylsulfonyl, alkylaminoalkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, heterocyclylsulfonyl, alkenylsulfonyl, etc. Examples of disulfanyl (-S-S-R) include alkyldisulfanyl, haloalkyldisulfanyl, cycloalkyldisulfanyl, aralkyldisulfanyl, heteroarylalkyldisulfanyl, heterocyclylalkyldisulfanyl, alkoxyalkyldisulfanyl, alkylaminoalkyldisulfanyl, aryldisulfanyl, heteroaryldisulfanyl, heterocyclyldisulfanyl, alkenyldisulfanyl, etc. Sulfonylamino (-NH-SO ２ Examples of -R include alkylsulfonylaminos, haloalkylsulfonylaminos, cycloalkylsulfonylaminos, aralkylsulfonylaminos, heteroarylalkylsulfonylaminos, heterocyclylalkylsulfonylaminos, cycloalkylalkylsulfonylaminos, heterocyclylalkylsulfonylaminos, alkoxyalkylsulfonylaminos, alkylaminoalkylsulfonylaminos, arylsulfonylaminos, heteroarylsulfonylaminos, heterocyclylsulfonylaminos, alkenylsulfonylaminos, etc. Aminosulfonyl (-SO ２ Examples of -NR(R') include aminosulfonyl groups in which R and R' are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and aralkyl, or in which R and R' are groups that form a ring containing the nitrogen atom to which they are bonded. ２Examples of -NR(R') include groups R and R' independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl, alkynyl, aryl, heteroaryl, and aralkyl, or sulfamoylaminos having groups that form a ring containing a nitrogen atom to which they are bonded.

[0050] In this specification, "substituent containing a boron atom" means boranyl (-BR(R')) or trifluoroborate salt (-BF ３ － Examples include the following. Examples of boranyl(-BR(R')) include R and R' being independently selected from alkyl, cycloalkyl, aryl, heteroaryl, aralkyl, alkoxy, cycloalkoxy, aryloxy, heteroaryloxy, and aralkoxy groups, or R and R' forming a ring together with the boron atom to which R and R' are each bonded (i.e., a cyclic boryl group). Specific examples of substituents containing boron atoms include dimethylboranyl, dimethoxyboranyl, 1,3,2-dioxaborolan-2-yl, and 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl.

[0051] In this specification, "substituents containing a silicon atom" means silyl(-Si-R(R')(R'')), silyloxy(-O-Si-R(R')(R'')), and bissilylamino(-N-(Si-R(R')(R'')) ２ Examples include the following. These three substituents R, R', and R'' may be independently selected from alkyl, cycloalkyl, aryl, heteroaryl, and aralkyl groups. Specific examples of substituents containing a silicon atom include trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, triethylsilyloxy, t-butyldiphenylsilyloxy, and bistrimethylsilylamino.

[0052] In this specification, "substituents containing a phosphorus atom" means phosphoryl(-P(O)-R(R')), phosphoryloxy(-O-P(O)-R(R')), phospho(-PO ３ H２ Examples include the following. Examples of phosphoryl(-P(O)-R(R')) include diarylphosphoryl or diaryloxyphosphoryl, more specifically diphenylphosphoryl or diphenyloxyphosphoryl. Examples of phosphoryloxy(-O-P(O)-R(R')) include diC １ ~C ６ Alkyl phosphoryloxy, more specifically dimethyl phosphoryloxy, diethyl phosphoryloxy, or diC １ ~C ６ Examples include alkoxyphosphoryloxy compounds, more specifically dimethoxyphosphoryloxy compounds and diethoxyphosphoryloxy compounds.

[0053] In this specification, a "substituent containing a zinc atom" refers to an alkylzinc group (-Zn-C1 to C6 alkyl) or a zinc halide group (-Zn-X). Preferred "substituents containing a zinc atom" include -ZnMe, -ZnEt, -ZnPr, -ZnCl, -ZnBr, and -ZnI. Compounds having these "substituents containing a zinc atom" can be prepared by referring to March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (8th edition, John Wiley & Sons, Inc. 2019) or Comprehensive Organic Transformations (3rd edition, John Wiley & Sons, Inc. 2018) by RC Larock.

[0054] In this specification, “may be substituted” means that any substituted position of any group is either unsubstituted or substituted with one or more functional groups. Such functional groups are not particularly limited and include, for example, deuterium, halogen, cyano, nitro, hydroxy, thio, amino, carboxy, oxo, sulfonyl, phosphoryl, boranyl, C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C ３ ~C６ Cycloalkyl, C ６ ~C １４ Aryl, 5-14 member heteroaryl, C ７ ~C １４ Aralkyl, 5-10 member heteroaryl C １ ~C ６ Alkyl, 3-14 member heterocyclyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C １ ~C ６ Alkylsulfanyl C １ ~C ６ Alkyl, C １ ~C ６ Alkyl sulfinyl C １ ~C ６ Alkyl, C １ ~C ６ Alkylsulfonyl C １ ~C ６ Alkyl, C １ ~C ６ Carboxyalkyl, C ７ ~C １４ Aralcoxyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, 5-10 member heteroaryl C １ ~C ６ Alkyl, 4-7 member heterocyclyl C １ ~C ３ Alkyl, 5-10 member heteroaryl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, aminocarbonyl (where the amino is -NH ２ Mono C １ ~C ６ Alkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C １ ~C ６ Alkoxy C １ ~C ６ (Alkylamino, or 4-9 membered cyclic amino), C １ ~C ６ Alkoxy, C ３ ~C １０ Cycloalkoxy, C ６ ~C １４ Aryloxy, 5-14 member heteroaryloxy, C ６ ~C １０ Aryl C １ ~C １０ Alkoxy, 5-10 member heteroaryl C １ ~C ６ Alkoxy, 3-14 member heterocyclyloxy, 3-14 member heterocyclyl C １ ~C ６ Alkoxy, C ２ ~C ６ Alkenyloxy, aminocarbonyl, C １ ~C ６ Alkyl sulfanyl, C １ ~C ６ Alkyl sulfinyl, C １ ~C ６ Alkyl sulfonyl, C ６ ~C １４ The functional groups are selected from the group consisting of arylsulfonyls, 5- to 14-membered heteroarylsulfonyls, and acyls, and these functional groups may be further substituted with acceptable functional groups. The substituents may also be selected from the group consisting of substituents containing an oxygen atom, a nitrogen atom, a sulfur atom, a boron atom, a silicon atom, a phosphorus atom, and a zinc atom.

[0055] In this specification, "alicyclic ring" refers to a saturated or partially saturated non-aromatic hydrocarbon ring. The carbon atoms constituting the ring may be oxidized to include carbonyl atoms. Alicyclic rings may be selected from the group consisting of monocyclic rings, fused rings, and spirocyclic rings. In this specification, an alicyclic ring containing a monocyclic ring is referred to as a monocyclic alicyclic ring, an alicyclic ring containing a fused ring is referred to as a fused-ring alicyclic ring, and an alicyclic ring containing a spirocyclic ring is referred to as a spirocyclic alicyclic ring. Alicyclic rings may form fused rings with saturated alicyclic rings such as cyclopentane rings or cyclohexane rings, unsaturated alicyclic rings such as cycloheptene rings or cyclohexene rings, or aromatic hydrocarbon rings such as benzene rings or naphthalene rings. For example, an alicyclic ring may form a spirocyclic ring with saturated alicyclic rings such as cyclopropane rings, cyclobutane rings, cyclopentane rings, or cyclohexane rings. Examples of alicyclic rings include C ３ ~C １０ It is an alicyclic ring, C ３ ~C ８ A alicyclic ring is preferred, C ３ ~C ７ A alicyclic ring is more preferred, C ３ ~C ６ Alicyclic rings are most preferred. Examples of alicyclic rings include cyclopropane rings, cyclobutane rings, cyclopentane rings, cyclohexane rings, cycloheptane rings, cyclooctane rings, bicyclo[2.2.1]heptane rings, and cyclohexene rings.

[0056] In this specification, "saturated alicyclic ring" refers to an alicyclic ring that does not have unsaturated bonds between the carbon atoms constituting the ring. Examples of saturated alicyclic rings include C ３ ~C １０ It is a saturated alicyclic ring, C ３ ~C ８ A saturated alicyclic ring is preferred, C ３ ~C ７ A saturated alicyclic ring is more preferred, C ３ ~C ６ Saturated alicyclic rings are most preferred. Specific examples of saturated alicyclic rings include cyclopropane rings, cyclobutane rings, cyclopentane rings, cyclohexane rings, cycloheptane rings, cyclooctane rings, and bicyclo[2.2.1]heptane rings.

[0057] In this specification, "heterocycle" refers to a ring that, in addition to carbon atoms, contains, preferably, 1 to 5, more preferably 1 to 3, heteroatoms selected from the group consisting of nitrogen atoms, oxygen atoms, and sulfur atoms, and may have double and / or triple bonds within the ring. The carbon atoms constituting the heterocycle may be oxidized to form carbonyls. In this specification, a heterocycle containing a monocycle is referred to as a monocyclic heterocycle, a heterocycle containing a fused ring is referred to as a fused heterocycle, and a heterocycle containing a spirocycle is referred to as a spirocyclic heterocycle. A heterocycle may form a fused ring with, for example, a saturated alicyclic ring such as a cyclopentane ring or a cyclohexane ring, an unsaturated alicyclic ring such as a cyclohexene ring, a saturated heterocycle such as a tetrahydropyran ring, a dioxane ring, or a pyrrolidine ring, an aromatic hydrocarbon ring such as a benzene ring or a naphthalene ring, or a pyridine ring, pyrimidine ring, or pyrazine ring. For example, the heterocycle may form a spiro ring with saturated alicyclic rings such as cyclopentane or cyclohexane rings, unsaturated alicyclic rings such as cyclohexene rings, or saturated heterocycles such as tetrahydropyran rings, dioxane rings, or pyrrolidine rings. The number of atoms constituting the heterocycle is 3 to 14 (3 to 14-membered heterocycle), preferably 3 to 12 (3 to 12-membered heterocycle), more preferably 3 to 10 (3 to 10-membered heterocycle), and most preferably 4 to 7 (4 to 7-membered heterocycle). Examples of heterocycles include azetidine rings, oxirane rings, oxetane rings, thietan rings, tetrahydrofuran rings, pyrrolidine rings, pyrazolidine rings, imidazolidine rings, oxazolidine rings, isoxazolidine rings, thiazolidinated rings, isothiazolidine rings, thiadiazolidinated rings, oxoxazolidine rings, dioxolane rings, tetrahydropyran rings, morpholine rings, thiomorpholine rings, 4-oxopyrrolidine rings, piperidine rings, 4-oxopiperidine rings, piperazine rings, dioxane rings, or rings in which one or more single bonds in these saturated heterocycles are replaced by double or triple bonds.

[0058] In this specification, a "saturated heterocycle" is a heterocycle that does not contain unsaturated bonds. In this specification, a saturated heterocycle that includes a monocycle is called a monocyclic saturated heterocycle. The number of atoms constituting the ring of a saturated heterocycle is 3 to 14 (3 to 14-membered heterocycle), preferably 3 to 12 (3 to 12-membered heterocycle), more preferably 3 to 10 (3 to 10-membered heterocycle), and most preferably 4 to 7 (4 to 7-membered heterocycle). Examples of saturated heterocycles include azetidine rings, oxirane rings, oxetane rings, thietan rings, tetrahydrofuran rings, pyrrolidine rings, pyrazolidine rings, imidazolidine rings, oxazolidine rings, isoxazolidine rings, thiazolidinated rings, isothiazolidine rings, thiadiazolidinated rings, oxoxazolidine rings, dioxolane rings, tetrahydropyran rings, morpholine rings, thiomorpholine rings, 4-oxopyrrolidine rings, piperidine rings, 4-oxopiperidine rings, piperazine rings, and dioxane rings.

[0059] In one embodiment, the present invention relates to a compound represented by the following formula (1) or a salt thereof. The compound of formula (1) has a ring composed of 11 amino acid residues. In this specification, P in the formula １ Q １ , and R １ The amino acid residue having core 1, P ２ Q ２ , and R ２ The amino acid residue having core 2, P ３ Q ３ , and R ３ The amino acid residue having core 3, P ４ Q ４ , and R ４ The amino acid residue having core 4, P ５ Q ５ , and R ５ The amino acid residue having core 5, P ６ Q ６ , and R ６ The amino acid residue having core 6, P ７ Q ７ , and R ７ The amino acid residue having core 7, P ８ Q ８ , and R８ The amino acid residue having core 8, P ９ Q ９ , and R ９ The amino acid residue having core 9, P １０ Q １０ , and R １０ The amino acid residue having the core 10, P １１ Q １１ , R １１ , and L １１ Amino acid residues containing this are sometimes referred to as core 11 amino acid residues.

[0060] In one embodiment, the present invention relates to a compound represented by the following formula (2) or a salt thereof.

[0061] In one embodiment, in formula (1) or formula (2), R １ C １ ~C ６ Alkyl, or C ２ ~C ７ Alkenyl remains, preferably C １ ~C ６ It is alkyl, and more preferably methyl.

[0062] In one embodiment, in formula (1) or formula (2), P １ is a hydrogen atom, or C １ ~C ６ It is alkyl, preferably C １ ~C ６ It is alkyl, more preferably methyl, ethyl, or n-propyl.

[0063] In one embodiment, in formula (1) or formula (2), R １ and P １ R １ The carbon atom to which it is bonded, and P １ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C１ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The 4- to 7-membered monocyclic saturated heterocycle may be substituted with one or more groups independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring. In this embodiment, the 4- to 7-membered monocyclic saturated heterocycle is preferably a 5- to 6-membered monocyclic saturated heterocycle, more preferably a 5-membered monocyclic saturated heterocycle, and even more preferably a pyrrolidine ring.

[0064] In one embodiment, in formula (1) or formula (2), R １ and P １ The formula is as follows: (In the formula, *** and **** are P in formula (1) or (2), respectively.) １ The nitrogen atom and R to which it is bonded １ X represents the carbon atom to which it is bonded. １ is a hydrogen atom, halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkoxy, or C ６ ~C １４ It forms a ring represented by an aryl group. In this embodiment, X １ Preferably, halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkoxy, or C ６ ~C １４ It is aryl, and more preferably C １ ~C ６ It is alkyl, and more preferably methyl or ethyl.

[0065] In one embodiment, in formula (1) or formula (2), R １ and P １ The formula is as follows: (In the formulas, *** and **** are P in formula (1) or formula (2), respectively.) １ The nitrogen atom and R to which it is bonded １ X represents the carbon atom to which it is bonded. １ C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or C ６ ~C １４ It forms a ring represented by an aryl group. In this embodiment, X １ Preferably C １ ~C ６ It is alkyl, more preferably methyl or ethyl.

[0066] In one embodiment, in formula (1) or formula (2), R １ R ６ Together with C ４ ~C ８ Alkylene, or C ４ ~C ８ Form an alkenylene, preferably R １ However, R ６ Together with it, it forms n-pentylene.

[0067] In one embodiment, in formula (1) or formula (2), R １ and P １ R １ The carbon atom to which it is bonded, and P １ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle is further X １ It is replaced with X １ is R ６ Together with C ４ ~C ８ Alkylene, or C ４ ~C ８ Form an alkenylene, preferably R １ and P １ However, R １The carbon atom to which it is bonded, and P １ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle is further X １ It is replaced with X １ is R ６ Together with C ４ ~C ８ Alkylene, or C ４ ~C ８ An alkenylene is formed. In this embodiment, the 4- to 7-membered monocyclic saturated heterocycle is preferably a pyrrolidine ring, X １ is R ６ Together with it, it forms 2-butenylene or 2-pentenylene.

[0068] In one embodiment, in formula (1) or formula (2), Q １ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0069] Specifically, as core 1, for example, MeAla, Pro, EtAla, Oic, Pic(2), Azp(2), Pro(4S-Me), Pro(4R-Al), Pro(5S-Me), Hyp( Et), cisHyp(CF3), Pro(5R-Ph), Pro(Me2), Pro(4S-F), Pro(5S-Et), cisHyp(Me), Pro(4S5-C3), Pro(5R-M e), Pro(5R-Et), Pic(2)(4S-OMe), Pro(4S5-C5), Pic(2)(4S-Me), Mor(3)(6S-Me), Mor(3)(6R-Me), Mor(3 )(2R-Me), Mor(3)(6-Me2), Mor(3), Pro(4S-Et), nPrAla, Pro(5S-MeOMe), Pro(4S5-C1), and MeAlgly.

[0070] In one embodiment, in formula (1) or formula (2), R ２ The formula is as follows: (In the formulas, * indicates R in formula (1) or formula (2)) ２ X represents the carbon atom to which it is bonded. ２１ C １ ~C ６Alkyl, C １ ~C ６ Alkoxy, or Halo C １ ~C ６ It is alkyl, X ２２ is a hydrogen atom, or C １ ~C ６ It is alkyl, X ２３ is a hydrogen atom, or C １ ~C ６ It is represented as an alkyl group. In this embodiment, preferably X ２１ C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or Halo C １ ~C ６ It is alkyl, X ２２ C １ ~C ６ It is alkyl, X ２３ is a hydrogen atom. In this embodiment, more preferably, X ２１ C １ ~C ６ It is alkyl, X ２２ C １ ~C ６ It is alkyl, X ２３ This is a hydrogen atom.

[0071] In one embodiment, in formula (1) or formula (2), R ２ The formula is as follows: (In the formulas, * indicates R in formula (1) or formula (2)) ２ X represents the carbon atom to which it is bonded. ２１ is, X ２１ and X ２２ Together with the bonded carbon atoms, they form a 3- to 8-membered saturated alicyclic ring, X ２３ is a hydrogen atom, or C １ ~C ６ It is represented as an alkyl group. In this embodiment, X ２３ Preferably, it is a hydrogen atom.

[0072] In another embodiment, in formula (1) or formula (2), R ２The compound is 1-methylpropyl, 1-methoxyethyl, 1-methylethyl, or ethyl, and is preferably 1-methylpropyl.

[0073] In one embodiment, in formula (1) or formula (2), R ２ Examples include ethyl, 1-methylpropyl, cyclohexyl, cyclobutyl, cyclopentyl, cyclopropyl, 1-methylpropyl, 2-methylpropyl, n-butyl, n-propyl, 1-ethoxyethyl, 1-methoxyethyl, 1-(n-propoxy)ethyl, 1-methylethyl, 1,1-dimethylpropyl, 2,2,2-trifluoro-1-methylethyl, and 1-methoxyethyl.

[0074] In one embodiment, in formula (1) or formula (2), P ２ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0075] In one embodiment, in formula (1) or formula (2), Q ２ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0076] As for core 2, specifically, examples include Ile, Thr(Et), Thr(nPr), Val(3-Et), Val, Chg, Thr(Me), Gly(cPent), aIle, aThr(Me), Gly(cBu), Gly(cPr), Abu, Nva, Leu, Nle, and Val(3R-4-F3).

[0077] In one embodiment, in formula (1) or formula (2), R ３ C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C３ ~C ８ Cycloalkyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, C ６ ~C １４ Aryloxy C １ ~C ６ Alkyl, or C ７ ~C １４ It is an aralkyl, and each of them is a halogen, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys. ３ C may preferably be substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ C is alkyl, and more preferably substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ C is alkyl, and more preferably substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ C is alkyl, and more preferably substituted with one or more halogens. ５~C ７ Cycloalkoxy C １ ~C ６ C is alkyl, and most preferably may be substituted with one or more halogens. ６ Cycloalkoxy C １ ~C ６ It is alkyl, and particularly preferably (cyclopentoxy)methyl, (cyclohexoxy)methyl, or (cycloheptoxy)methyl.

[0078] In one embodiment, in formula (1) or formula (2), R ３ As such, (cyclohexyloxy)methyl, 2-cyclohexylethyl, (cycloheptyloxy)methyl, 2-phenylethyl, (cyclopentoxy)methyl, (3-methylbutoxy)methyl, (2-methylpropoxy)methyl, 2-(cyclopentyl)ethyl, (cyclobutoxy)methyl, (2-chlorophenoxy)methyl, 2-(cyclohexyllidene)ethyl, 2-(3-chlorophenyl)ethyl, (cyclopropoxy)methyl, (cyclohexylmethoxy)methyl, (cyclo Examples include propylmethoxymethyl, (2,2-dimethylpropoxy)methyl, (n-propoxy)methyl, (phenoxy)methyl, (2,2,2-trifluoroethoxy)methyl, (cyclohexoxy)methyl, 2-cycloheptylethyl, (3,3-difluorocyclobutoxy)methyl, 1-cyclohexyloxyethyl, 2-(ethoxy)ethyl, 2-(2,2,2-trifluoroethoxy)ethyl, 2-(cyclohexoxy)ethyl, and 2-phenoxyethyl.

[0079] In one embodiment, in formula (1) or formula (2), P ３ C is a hydrogen atom. １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, preferably C １ ~C ６ It is alkyl, and more preferably methyl.

[0080] In one embodiment, in formula (1) or formula (2), Q３ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0081] Specifically, as core 3, for example, MeHph, MeSer(Ph-2-Cl), Ser(Ph-2-Cl), MeHch, MeHph(3-Cl), MeSer(cHex), MeSer(Ph), MeAbu(cPent), Hch, MeSer(Me-cHex), MeAbu(cHexdene), MeAbu(cHep), MeSer(cPent), MeSer(cBu), MeSer(cHep), MeSer(iPen), MeSer(iBu), MeSer(Tfe), MeSer( cBu-3-F2), EtSer(cHex), Ser(cHex), MeSer(Me-cPr), MeSer(neoPent), EtSer(iPen), MeSer(nPr), MeSer(cHex-4-F2), MeHse(Et), Me Examples include Hse (Tfe), MeHse (cHex), MeHse (Ph), MeSer (cPr), nPrSer (cHex), nBuSer (cHex), cPrMeSer (cHex), EtSer (cHep), and MeThr (cHex).

[0082] In one embodiment, in formula (1) or (2), R ４ C is a hydrogen atom. １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ It is an alkyl group, preferably a hydrogen atom, C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ It is alkyl.

[0083] In one embodiment, in formula (1) or formula (2), P ４ is a hydrogen atom, or C １ ~C ６ It is alkyl, preferably C １ ~C ６It is alkyl, and more preferably methyl.

[0084] In one embodiment, in formula (1) or formula (2), Q ４ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is an alkyl group, and each of them may be substituted with one or more halogens. In this embodiment, Q ４ Preferably a hydrogen atom, or C １ ~C ６ It is alkyl, and more preferably methyl.

[0085] In one embodiment, in formula (1) or formula (2), R ４ and P ４ R ４ The carbon atom to which it is bonded, and P ４ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups selected more independently from the group consisting of aryl groups. In this embodiment, the 4- to 7-membered monocyclic saturated heterocycle is preferably a 5-membered monocyclic saturated heterocycle, and more preferably a pyrrolidine ring.

[0086] In one embodiment, in formula (1) or formula (2), R ４ and Q ４ R ４ and Q ４ Together with the bonded carbon atoms, they form a 3- to 8-membered saturated alicyclic ring.

[0087] In one embodiment, in formula (1) or formula (2), R ４ and P ４ R ４ The carbon atom to which it is bonded, and P ４ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, Q ４ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, 5-10 member heteroaryl C １ ~C ６ Alkyl, Halo C １ ~C ６ C which may be substituted with alkyl or halogen ７ ~C １４ It is aralkyl, preferably R ４ and P ４ R ４ The carbon atom to which it is bonded, and P ４ Together with the nitrogen atom to which it is bonded, it forms an azetidine ring, a pyrrolidine ring, and a piperidine ring, Q ４ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, 5-10 member heteroaryl C １ ~C ６Alkyl, Halo C １ ~C ６ C which may be substituted with alkyl or halogen ７ ~C １４ It is Aalkyl, and more preferably, R ４ and P ４ R ４ The carbon atom to which it is bonded, and P ４ Together with the nitrogen atom to which it is bonded, it forms a pyrrolidine ring, Q ４ These are methyl, ethyl, 2-phenethyl, phenylmethyl, 2-fluorophenylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, 2-propa-2-inyl, buta-2-inyl, 2-fluoroethyl, 2,2-difluoroethyl, or methoxymethyl.

[0088] Specifically, the core 4 includes, for example, MeSer(nPr), MeSer(iPen), D-(Me)Pro, MeAla, D-(Me)Pic(2), D-(Me)Aze(2), D-Pro, D-(Phene)Pro, MeAib, MecLeu, Aib, D-(Bzl)Pro, D -(MeC#CMe)Pro, D-(4-PyrMe)Pro, D-(C#CMe)Pro, D-(Et)Pro, D-(CH2FMe)Pro, D-(CHF2Me)Pro, D-(MeOMe)Pro, D-(2-F-Bzl)Pro, and D-(3-PyrMe)Pro.

[0089] In one embodiment, in formula (1) or formula (2), R ５ is aminocarbonyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl (the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ C may be substituted with a cycloalkylamino or a 3- to 10-membered monocyclic cyclic amino, or a 4- to 7-membered heterocyclyl. １ ~C ６ Alkoxy C １ ~C ６ It is an alkyl group, preferably an aminocarbonyl C group. １ ~C ６ Alkoxy C １ ~C ６ Alkyl (the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ (It is a cycloalkylamino or a 3-10 member monocyclic cyclic amino), more preferably monoC １ ~C ６ Alkylaminocarbonyl C １ ~C ２ Alkoxy C １ ~C ２ Alkyl or mono-C ３ ~C ８ Cycloalkylaminocarbonyl C １ ~C ２ Alkoxy C １ ~C ２ It is alkyl, and more preferably mono-C. １ ~C ６ Alkylaminocarbonyl C １ ~C ２ Alkoxy C １ ~C２ It is an alkyl group, most preferably [(t-butylamino)carbonyl]methoxymethyl.

[0090] In one embodiment, in formula (1) or formula (2), R ５ Examples include [(t-butylamino)carbonyl]methoxymethyl, [(cyclopentylamino)carbonyl]methoxymethyl, [(1,1-dimethylpropylamino)carbonyl]methoxymethyl, [(1-methylcyclobutyl)carbonyl]methoxymethyl, [[(3S)-tetrahydrofuran-3-yl]methoxymethyl, [[(3R)-tetrahydrofuran-3-yl]methoxymethyl, [(1-methylcyclopropylamino)carbonyl]methoxymethyl, [[(2R)-oxetane-2-yl]methoxymethyl, and [[(2S)-oxetane-2-yl]methoxymethyl.

[0091] In one embodiment, in formula (1) or formula (2), P ５ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0092] In one embodiment, in formula (1) or formula (2), Q ５ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0093] Specific examples of the five cores include, for instance, Ser(NtBu-Aca), Ser(NcPent-Aca), Ser(NtAmyl-Aca), Ser(N(1-Me-cBu)-Aca), Ser(Me-3S-THF), Ser(Me-3R-THF), Ser(Me-2R-Oxe), Ser(Me-2S-Oxe), and Ser(N(1-Me-cPr)-Aca).

[0094] In one embodiment, in formula (1) or formula (2), R ６ The formula is as follows: (In the formula, ** is R in formula (1) or formula (2)) ６ X represents the carbon atom to which it is bonded. ６１ C is a hydrogen atom.１ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C １ ~C ６ Alkoxy, or C ３ ~C ８ It is a cycloalkoxy, X ６２ is a hydrogen atom, or C １ ~C ６ It is alkyl, X ６３ is a hydrogen atom, or C １ ~C ６ It is represented as an alkyl group.

[0095] In one embodiment, in formula (1) or formula (2), R ６ The formula is as follows: (In the formula, ** is R in formula (1) or formula (2)) ６ X represents the carbon atom to which it is bonded. ６１ is, X ６１ and X ６２ Together with the bonded carbon atoms, these atoms form a 3-8 member saturated alicyclic ring or a 4-7 member saturated heterocyclic ring, and these 3-8 member saturated alicyclic rings or 4-7 member saturated heterocyclic rings contain halogens, C １ ~C ６ Alkyl and C １ ~C ６ X may be substituted with one or more groups independently selected from the group consisting of alkoxys. ６３ is a hydrogen atom, or C １ ~C ６ It is represented as an alkyl group.

[0096] In one embodiment, in formula (1) or formula (2), R ６ Examples include cyclopentyl, buta-3-enyl, 1-methylpropyl, methyl, propa-2-enyl, cyclohexyl, cyclobutyl, cyclopropyl, 1-ethylpropyl, 1-methoxyethyl, 1-methylethyl, 3,3-difluorocyclobutyl, 1-ethoxyethyl, oxan-4-yl, cycloheptyl, 4,4-difluorocyclohexyl, 1-isopropyloxyethyl, and 1-cyclobutoxyethyl.

[0097] In one embodiment, in formula (1) or formula (2), P ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, preferably C １ ~C ６ It is alkyl, more preferably methyl, or ethyl, and even more preferably methyl.

[0098] In one embodiment, in formula (1) or formula (2), Q ６ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0099] Specifically, the Core 6 includes, for example, MeAla, MeGly(cPent), MeChg, MeAlgly, MeAhxe(2), MeGly(cBu), MeGly(cBu-3-F2), MeGly(cPr), MeVal, MeaThr(Me), MeThr(Me), MeIle, MeaIle, MeaThr(Et), MeChg(4-F2), MeaThr(iPr), MeaThr(cBu), EtGly(cPent), EtGly(cBu), MeGly(4-THP), MeNva(3-Et), and MeGly(cHep).

[0100] In one embodiment, in formula (1) or formula (2), R ７ C １ ~C ６ It is alkyl, preferably C １ ~C ３ It is alkyl, and more preferably methyl.

[0101] In one embodiment, in formula (1) or formula (2), P ７ is a hydrogen atom, or C １ ~C ６ It is alkyl, preferably C １ ~C ６ It is alkyl, and more preferably methyl.

[0102] In one embodiment, in formula (1) or formula (2), R ７ and P ７ R ７The carbon atom to which it is bonded, and P ７ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered saturated heterocycle, and this 4- to 7-membered saturated heterocycle is a halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups more independently selected from the group consisting of aryl groups. In this embodiment, the 4- to 7-membered saturated heterocycle is preferably a 4 or 5-membered saturated heterocycle, more preferably a 5-membered saturated heterocycle, and even more preferably a pyrrolidine ring.

[0103] In one embodiment, in formula (1) or formula (2), Q ７ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0104] Specific examples of Core 7 include Pro, MeAbu, Ala, Pro(4S-F), Pro(4R-F), Pro(4R-Me), MeAla, and Aze(2).

[0105] In one embodiment, in formula (1) or formula (2), R ８ C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６It may be substituted with one or more groups independently selected from the group consisting of alkoxys, preferably C ３ ~C ８ It is cycloalkyl, and more preferably cyclopropyl.

[0106] In one embodiment, in formula (1) or formula (2), R ８ Examples include cyclopropyl, methyl, cyclobutyl, cyclopropyl, 1-methylethyl, 1-hydroxyethyl, and ethyl.

[0107] In one embodiment, in formula (1) or formula (2), R ８ C ３ ~C ８ It is a cycloalkyl, P ８ C １ ~C ６ It is alkyl.

[0108] In one embodiment, in formula (1) or formula (2), R ８ It is preferably cyclopropyl, and P ８ The compound is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, or 2-methylpropyl.

[0109] In one embodiment, in formula (1) or formula (2), P ８ C is a hydrogen atom. １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, preferably C １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, more preferably C １ ~C ６ The alkyl group is more preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, or 2-methylpropyl, and even more preferably ethyl or n-propyl.

[0110] In one embodiment, in formula (1) or formula (2), R ８ and P ８ R ８ The carbon atom to which it is bonded, and P ８ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The 4- to 7-membered monocyclic saturated heterocycle may be substituted with one or more groups selected more independently from the group consisting of aryl groups, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a saturated carbon ring. In this embodiment, the 4- to 7-membered monocyclic saturated heterocycle is preferably an azepane ring.

[0111] In one embodiment, in formula (1) or formula (2), Q ８ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0112] The core 8 specifically includes, for example, Thr, Val, MeAla, MeVal, MeGly(cPr), Azp(2), Gly(cPr), nPrGly(cPr), Oic, Pro(4S5-C3), EtGly(cPr), EtGly(cBu), MeGly(cBu), Oazp(3), Oazp(5), nPrAla, nPrAbu, nBuGly(cPr), iBuGly(cPr), cPrMeGly(cPr), and iPrGly(cPr).

[0113] In one embodiment, in formula (1) or formula (2), R ９ C １ ~C ６Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, 4-7 member heterocyclyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkil, C ６ ~C １０ Aryloxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, 4-9 member heterocyclyloxy C １ ~C ６ Alkyl or 5-10 member heteroaryl C １ ~C ６ The C is alkyl, and each of them may be substituted with a halogen. ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl and 5-10 membered heteroaryl C １ ~C ６ Alkyl is C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy and Halo C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys.

[0114] In one embodiment, in formula (1) or formula (2), R ９ Preferably C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is alkyl, and the C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ Alkyls are halogens, and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[0115] In one embodiment, in formula (1) or formula (2), R ９ It is comfortable C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is alkyl, and the C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ Alkyls are halogens, and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[0116] In one embodiment, in formula (1) or formula (2), R ９ C ６ Aryl C １ ~C ２ Alkyl or 6-membered heteroaryl C １ ~C ２ It is alkyl, and the C ６ Aryl C １ ~C ２ Alkyl or 6-membered heteroaryl C １ ~C ２ Alkyls are halogens, and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkyl groups.

[0117] In one embodiment, in formula (1) or formula (2), R ９As such, 2-phenylethyl, ethyl, 2-(pyridine-3-yl)ethyl, 2-(pyridine-4-yl)ethyl, 2-(cyclohexylidene)ethyl, 2-cyclopropylethyl, 3,3-dimethylbutyl, 2-(4-tetrahydropyran-4-yl)ethyl, buta-3-enyl, buta-3-inyl, methyl, 2-cyclohexylethyl, 3-methylbutyl, 5,5-difluoropentyl, 2-(2-fluorophenyl)ethyl, 2-(3-chlorophenyl)ethyl, 2-(3-fluorophenyl)ethyl, 2-(3-methoxyphenyl)ethyl, 2-[4-(trifluoromethyl)phenyl]ethyl, 2-(4-chlorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, 2-(methoxy)ethyl, 1-methylpropyl, n-butyl, 3,3-difluoro Ropropyl, 3,3,3-trifluoropropyl, (cyclohexyloxy)methyl, (propan-2-yloxy)methyl, (phenoxy)methyl, (2-chlorophenoxy)methyl, (2,2,2-trifluoroethoxy)methyl, (2-methylpropoxy)methyl, (3,3-difluorocyclobutoxy)methyl, 2-(ethoxy)ethyl, 2-(2,2,2-trifluoroethoxy)ethyl, 2-(cyclohexoxy)ethyl, 2-phenoxyethyl, 2-(6-oxo-1H-pyridine-3-yl)ethyl, 2-(1-methyl-6-oxo-3-pyridyl)ethyl, 2-(1,3-benzoxazole-6-yl)ethyl, 2-(imidazo[1,2-a]pyridine-6-yl)ethyl, 2-[4-(difluoromethoxy)phenyl]ethyl, 2-(3,4-Difluorophenyl)ethyl, 2-(3-iodophenyl)ethyl, 2-(2-methylindazole-5-yl)ethyl, 2-(2-fluoro-4-pyridyl)ethyl, 2-(6-fluoro-3-pyridyl)ethyl, 2-(1-naphthyl)ethyl, 2-(1-methylcyclopropyl)ethyl, 2-(2-methyl-3-pyridyl)ethyl, 2-(3-fluoro-4-pyridyl)ethyl, 2-(2-methoxy-3-pyridyl)ethyl, 2-(2-methoxyphenyl Examples include ethyl, 2-(5-methoxy-3-pyridyl)ethyl, (t-butoxy)methyl, 2-(3-methyl-4-pyridyl)ethyl, 2-(3-chloro-4-pyridyl)ethyl, 2-(4-methyl-3-pyridyl)ethyl, 2-(2-pyridyl)ethyl, 4,4,4-trifluorobutyl, (tetrahydropyran-4-yloxy)ethyl, 2-(3,5-difluoro-4-pyridyl)ethyl, and 2-[3-(trifluoromethyl)-4-pyridyl]ethyl.

[0118] In one embodiment, in formula (1) or formula (2), R ９ These are 2-phenylethyl, 2-(2-fluorophenyl)ethyl, 2-(4-fluorophenyl)ethyl, (3-fluoro-4-pyridyl)ethyl, or (3-chloro-4-pyridyl)ethyl.

[0119] In one embodiment, in formula (1) or formula (2), P ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, preferably C １ ~C ６ It is alkyl, more preferably methyl, or ethyl, and even more preferably methyl.

[0120] In one embodiment, in formula (1) or formula (2), Q ９ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0121] Specifically, the core 9 includes, for example, MeHph, MeAbu(5-Pyrido), EtHph, MeHle, MeAbu(tBu), MeHph(4-CF3), MeAbu(3-Pyr), MeSer(Ph-2-Cl), MeAbu(5-Pyrido-1-Me), MeAbu(4-Pyr), MeHph(3-OMe), MeHph(3-Cl), MeSer(Ph), MeHph(4-Cl), MeHph(3-I), MeSer(iPr), and MeAhx. e(2), MeAbu(cHexdene), MeAbu(4-Pyr-3-F), MeAbu(3-Pyr-2-OMe), MeSer(iBu), MeAbu(4-(1-Me-cPr)), MeAbu(3-Pyr-2-Me) , MeHph(2-OMe), MeHph(2-F), MeAla, MeAbu, MeIle, MeNle, MeAbu(cPr), MeHch, MeAbu(THP), MeAbu(3-Pyr-5-OMe), MeAhxy(2) , MeNva(5-F3), MeNva(5-F2), MeSer(tBu), MeSer(Tfe), MeHnl(7-F2), MeSer(cBu-3-F2), MeNle(6-F3), MeHph(4-F), MeSer(c Hex), MeHph(3-F), MeAbu(4-Pyr-3-Me), MeAbu(4-Pyr-3-Cl), MeAbu(3-Pyr-4-Me), MeHse(Et), MeHse(cHex), MeHse(Ph), MeH Examples include se(Me), MeHse(Tfe), MeHse(4-THP), MeAbu(4-Pyr-35F2), MeAbu(4-Pyr-3-CF3), MeAbu(2-Pyr), MeHph(34-F2), MeAbu(6-BzOxa), MeAbu(6-Imipy), MeHph(4-OCF2H), MeAbu(1-Nap), MeAbu(5-Indaz-2-Me), MeAbu(4-Pyr-2-F), and MeAbu(3-Pyr-6-F).

[0122] In one embodiment, in formula (1) or formula (2), R １０ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0123] In one embodiment, in formula (1) or formula (2), P １０ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C ７ ~C １４ It is aralkyl, and each of them may be substituted with one or more halogens. In this embodiment, P １０ C may preferably be substituted with one or more halogens. １ ~C ６ Alkyl, or C ２ ~C ６ C is an alkenyl, and more preferably, may be substituted with one or more halogens. １ ~C ６ It is alkyl, and more preferably ethyl, n-butyl, or n-propyl.

[0124] In one embodiment, in formula (1) or formula (2), P １０ Examples include cyclopropylmethyl, 2-methoxyethyl, prop-2-enyl, benzyl, c-propyl, 2,2-difluoroethyl, 3,3-difluoropropyl, ethyl, 3-fluoropropyl, n-butyl, n-propyl, prop-2-inyl, 3,3,3-trifluoropropyl, 3,3-difluorocyclobutyl, c-butylmethyl, buta-2-inyl, buta-3-inyl, and 4,4,4-trifluorobutyl.

[0125] In one embodiment, in formula (1) or formula (2), Q １０ is a hydrogen atom, or C １ ~C ６It is an alkyl group, preferably a hydrogen atom.

[0126] Specifically, the core 10 includes, for example, nBuGly, (cPrMe)Gly, (MeOEt)Gly, TfpGly, (3-F2-cBu)Gly, cBuMeGly, BnGly, DfpGly, nPrGly, PraGly, AllylGly, MePraGly, ButynylGly, TfbGly, EtGly, DfeGly, MfpGly, cPrGly, and D-nPrAla.

[0127] In one embodiment, in formula (1) or formula (2), R １１ C is a hydrogen atom. １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, aminocarbonyl (where the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ The aminocarbonyl is a cycloalkylamino or a 3-10 membered cyclic amino, and if the aminocarbonyl is a 3-10 membered cyclic aminocarbonyl, it may be condensed with a 3-8 membered saturated alicyclic ring, and may form a spiro ring or a crosslinking ring on the ring, and the aminocarbonyl may be a halogen, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８It may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups.

[0128] In one embodiment, in formula (1) or formula (2), R １１ The is preferably a 3-10 member monocyclic cyclic aminocarbonyl, which may be condensed with a 3-8 member saturated alicyclic ring, or may form a spiro ring or a crosslinking ring on the ring, and the 3-10 member monocyclic cyclic aminocarbonyl may be halogen, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ It may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups.

[0129] An example of a 3- to 10-membered monocyclic aminocarbonyl that forms a cross-linking ring on the ring is (7-azabicyclo[2.2.1]heptan-7-yl)carbonyl.

[0130] In one embodiment, in formula (1) or formula (2), R １１ The more preferably is a 4 or 5-membered monocyclic cyclic aminocarbonyl, which may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl are halogens, C １ ~C ６ Alkyl, C １ ~C ６ Haloalkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ It may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups.

[0131] In one embodiment, in formula (1) or formula (2), R １１More preferably, the 4 or 5-membered monocyclic cyclic aminocarbonyl is a 4 or 5-membered monocyclic cyclic aminocarbonyl, which may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl are one or more halogens and one or more C １ ~C ６ It may be substituted with an alkyl group.

[0132] In one embodiment, in formula (1) or formula (2), R １１ is a 4 or 5-membered monocyclic cyclic aminocarbonyl, which may form a spiro ring on the ring, and the atoms forming the ring of the 4 or 5-membered monocyclic cyclic aminocarbonyl may be substituted with one or two substituents selected from fluorine, methyl, ethyl, propyl, and methoxy. In one embodiment, in formula (1) or formula (2), R １１ This is a 4- or 5-membered monocyclic cyclic aminocarbonyl, which may form a spiro ring on its ring, and the atoms forming the ring of the 4- or 5-membered monocyclic cyclic aminocarbonyl may be substituted with one substituent selected from fluorine, methyl, ethyl, propyl, and methoxy, or with two substituents selected from a combination of methyl and methyl, a combination of methyl and fluorine, a combination of ethyl and fluorine, a combination of fluorine and fluorine, a combination of methyl and methoxy, and a combination of methyl and ethyl.

[0133] In one embodiment, in formula (1) or formula (2), R １１For example, (3,3-dimethylpyrrolidine-1-yl)carbonyl, (pyrrolidine-1-yl)carbonyl, N,N-diethylaminocarbonyl, N-methyl-N-propyl-aminocarbonyl, (3,3-difluoropyrrolidine-1-yl)carbonyl, (2-azaspiro[3,3]heptan-2-yl)carbonyl, (azetidine-1-yl)carbonyl, ethyl, (2-oxa-6-azaspi (3.3)heptan-6-yl)carbonyl, (2R)-2-methylpyrrolidine-1-yl)carbonyl, (7-azabicyclo[2.2.1]heptan-7-yl)carbonyl, 2,2,2-trifluoroethyl, (3-ethylazetidine-1-yl)carbonyl, (3-azabicyclo[3.1.0]hexane-3-yl)carbonyl, (N-cyclopropyl-N-methylamino)carbonyl, (3-methylazetidine-1-yl)carbonyl, (3,3-difluoroazetidine-1-yl)carbonyl, (5-azaspiro[2.3]hexane-5-yl)carbonyl, (5-azaspiro[2.4]heptan-5-yl)carbonyl, (6-azaspiro[3.4]octan-6-yl)carbonyl, (3,3-dimethylazetidine-1-yl)carbonyl, (3-fluoro-3-methyl- Zethidine-1-yl)carbonyl, (3-ethyl-3-fluoroazetidine-1-yl)carbonyl, (3-isopropylazetidine-1-yl)carbonyl, (2-azaspiro[3.4]octan-2-yl)carbonyl, (3-propylazetidine-1-yl)carbonyl, (6,6-difluoro-2-azaspiro[3.3]heptan-2-yl)carbonyl, (3-azabicyclo[3.2.[0]Heptan-3-yl)carbonyl, (3-fluoro-3-propyl-azetidine-1-yl)carbonyl, (3-fluoroazetidine-1-yl)carbonyl, (3-methoxy-3-methylazetidine-1-yl)carbonyl, (3-ethyl-3-methylazetidine-1-yl), [(3R)-3-fluoro-3-methylpyrrolidine-1-yl]carbonyl, [(3R)-3-methylpyrrolidine] Examples include [zin-1-yl]carbonyl, [(3S)-3-methylpyrrolidine-1-yl]carbonyl, (3-methoxyazetidine-1-yl)carbonyl, (2,2-dimethylazetidine-1-yl)carbonyl, (6,6-dimethyl-3-azabicyclo[3.1.0]hexane-3-yl)carbonyl, and (6,6-difluoro-3-azabicyclo[3.1.0]hexane-3-yl)carbonyl.

[0134] In one embodiment, in formula (1) or formula (2), R １１ (3-ethylazetidine-1-yl)carbonyl, (2,2-dimethylazetidine-1-yl)carbonyl, (3-fluoro-3-methylazetidine-1-yl)carbonyl, (3-ethyl-3-fluoroazetidine-1-yl)carbonyl, (3,3-dimethylazetidine-1-yl)carbonyl, (3-ethyl-3-methylazetidine-1-yl)carbonyl, (2-azaspiro[3,3]heptan-2-yl (Azaspiro[3,4]octan-2-yl)carbonyl, (3,3-difluoropyrrolidine-1-yl)carbonyl, (3,3-dimethylpyrrolidine-1-yl)carbonyl, (3-azabicyclo[3.2.0]heptan-3-yl)carbonyl, (5-azapiro[2,4]heptan-5-yl)carbonyl, or (6-azapiro[3,4]octan-6-yl)carbonyl.

[0135] In one embodiment, in formula (1) or formula (2), P １１ is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0136] In one embodiment, in formula (1) or formula (2), Q １１is a hydrogen atom, or C １ ~C ６ It is an alkyl group, preferably a hydrogen atom.

[0137] In one embodiment, in formula (1) or formula (2), L １１ It is either a single bond or -CM １１ M １２ -, - (CH ２ ) ｎ S (CH ２ ) ｍ -, - (CH ２ ) ｎ S(O)(CH ２ ) ｍ - or - (CH ２ ) ｎ S(O) ２ (CH ２ ) ｍ - where n and m are independently 1 or 2, and M １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, M １２ is a hydrogen atom, or C １ ~C ６ It is alkyl.

[0138] In one embodiment, in formula (1) or formula (2), L １１ Preferably -CM １１ M １２ - and M １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, M １２ is a hydrogen atom, or C １ ~C ６ It is alkyl.

[0139] In one embodiment, in formula (1) or formula (2), L １１ is comfortable-CH ２ - is the case.

[0140] Specifically, as core 11, for example, Asp-pyrro, D-3-Abu, bAla, bAla(2-Me2), R-AMPA, bAla(2R-Et), Asp-aze(3s-cBu), Asp-NEt2, Asp-pyrro(3-F2), MeAsp-pyrro, Asp-pip, Asp-aze(3-Et), Asp-NMecPr, bAla(3R-Et), bAla(3S- CH2CF3), Asp-aze(3-F-3-Me), Asp-aze(3-F-3-Et), Asp-aze(3-Me2), Asp-pyrro(3-Me2), Asp-pyrro(2R- Me), Asp-aze(3s-oxe), Asp-pyrro(25-C2), Asp-MeNnPr, Asp-aze, Asp-pyrro(34-C1), Asp-aze(3-Me), As p-aze(3-F2), Asp-aze(3s-cPr), Asp-pyrro(3s-cPr), Asp-pyrro(3s-cBu), Asp-aze(3-iPr), Asp-aze(3- F-3-nPr), Asp-aze(3-F), Asp-aze(3-Me-3-Et), Asp-pyrro(3R-F-3-Me), Asp-pyrro(3S-Me), Asp-aze(3- Examples include OMe), Asp-aze(3s-cPent), Asp-aze(3-nPr), Asp-aze(3s-cBu(3-F2)), Asp-pyrro(34-C2), Asp-aze(3-Me-3-OMe), Asp-pyrro(3R-Me), Asp-aze(2-Me2), Asp-pyrro(34-C1(Me2)), and Asp-pyrro(34-C1(F2)).

[0141] In one embodiment, in formula (1) or formula (2), P １ ~P １１ At least four, five, six, seven, or eight of them are not hydrogen atoms.

[0142] In one embodiment, the present invention relates to a compound represented by the following formula (3) or a salt thereof.

[0143] In one embodiment, the present invention relates to a compound represented by the following formula (4) or a salt thereof.

[0144] In equation (3) or equation (4), R ２ , P ２ Q ２ , R ３ , P ３ Q ３ Q ４ , R ６ , P ６ , R ７ , P ７ Q ７ , R ８ , P ８ Q ８ , R ９ , P ９ Q ９ , P １０ , R １１ , P １１ , and Q １１ R in equation (1) or equation (2) above is ２ , P ２ Q ２ , R ３ , P ３ Q ３ Q ４ , R ６ , P ６ , R ７ , P ７ Q ７ , R ８ , P ８ Q ８ , R ９ , P ９ Q ９ , P １０ , R １１ , P １１ , and Q １１に This is synonymous with what was explained earlier.

[0145] In one embodiment, in formula (3) or formula (4), X １ C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or C ６ ~C １４ It is aryl, preferably C １ ~C ６ It is alkyl, more preferably methyl or ethyl.

[0146] In one embodiment, in equation (3), n is either 1 or 2.

[0147] In one embodiment, in formula (3) or formula (4), X ５ C １ ~C ６ Alkyl, or C １ ~C ６ C may be substituted with alkyl. ３ ~C ８ It is a cycloalkyl, preferably C １ ~C ６ It is alkyl, and more preferably t-butyl.

[0148] In one embodiment, the present invention relates to the following amino acids or salts thereof: (2S)-2-(methylamino)-3-propane-2-yloxypropanoic acid, (2S)-4-cycloheptyl-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-(1-methylcyclopropyl)butanoic acid, (2S,3S)-3-ethoxy-2-(methylamino)butanoic acid, (2S)-2-(4,4-difluorocyclohexyl)-2-(methylamino)acetic acid, (2S)-2-(methylamino)-2-(oxan-4-yl)acetic acid, (2S)-2-(3,3-difluorocyclobutyl)-2-(methyl (2S)-2-cycloheptyl-2-(methylamino)acetic acid, (2S)-2-(methylamino)-3-(2-methylpropoxy)propanoic acid, (2S)-3-cyclopentyloxy-2-(methylamino)propanoic acid, (2S)-4-cyclopentyl-2-(methylamino)butanoic acid, (2S)-5,5-dimethyl-2-(methylamino)hexanoic acid, (2S)-4-(3-iodophenyl)-2-(methylamino)butanoic acid, (2S)-4-(2-methoxypyridine-3-yl)-2-(methylamino)butane Acids, (2S)-4-(5-methoxypyridine-3-yl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-pyridine-2-ylbutanoic acid, (2S)-2-(methylamino)-4-(4-methylpyridine-3-yl)butanoic acid, (2S)-4-(3,5-difluoropyridine-4-yl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-[3-(trifluoromethyl)pyridine-4-yl]butanoic acid, (2S)-4-(3-chloropyridine-4-yl)-2-(methylamino )butanoic acid, (2S)-2-(methylamino)-4-(3-methylpyridine-4-yl)butanoic acid, (2S)-4-(3-fluoropyridine-4-yl)-2-(methylamino)butanoic acid, (2S)-2-cyclobutyl-2-(ethylamino)acetic acid, (2S)-2-cyclopropyl-2-(ethylamino)acetic acid, (2S)-2-(ethylamino)-3-(3-methylbutoxy)propanoic acid, (2S)-2-cyclopropyl-2-(propylamino)acetic acid, (2R)-2-(propylamino)propanoic acid, (2S)-3-(3,3-Difluorocyclobutyl)oxy-2-(methylamino)propanoic acid, (2S)-3-(4,4-difluorocyclohexyl)oxy-2-(methylamino)propanoic acid, (2S)-3-(cyclohexylmethoxy)-2-(methylamino)propanoic acid, (2S)-3-(2,2-dimethylpropoxy)-2-(methylamino)propanoic acid, (2S)-2-amino-3-[[(3R)-oxolan-3-yl]methoxy]propanoic acid, (2S)-2-amino-3-[[(3S)-oxolan-3-yl]methoxy]propanoic acid (2S)-2-(methylamino)-4-(2-methylpyridine-3-yl)butanoic acid, (2S)-2-(methylamino)-4-(1-methyl-6-oxopyridine-3-yl)butanoic acid, (2S)-4-(2-fluorophenyl)-2-(methylamino)butanoic acid, (2S)-4-(2-methoxyphenyl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-[4-(trifluoromethyl)phenyl]butanoic acid, (2S)-4-(3-fluorophenyl)-2-(methylamino)butanoic acid, (2S)-4 -(4-fluorophenyl)-2-(methylamino)butanoic acid, (2S)-2-(methylamino)-4-(6-oxo-1H-pyridine-3-yl)butanoic acid, (2S)-2-amino-3-[2-[(1-methylcyclobutyl)amino]-2-oxoethoxy]propanoic acid, (2S)-2-amino-3-[2-[(1-methylcyclopropyl)amino]-2-oxoethoxy]propanoic acid, (2S)-2-amino-3-[2-(2 -methylbutan-2-ylamino)-2-oxoethoxy]propanoic acid, (2S)-2-amino-3-[[(2R)-oxetan-2-yl]methoxy]propanoic acid, (2S)-2-amino-3-[[(2S)-oxetan-2-yl]methoxy]propanoic acid, (2S,3S)-3-cyclobutyloxy-2-(methylamino)butanoic acid, (2S,3S)-2-(methylamino)-3-propan-2-yloxybutanoic acid, (2S)-4-cyclohexylidene-2-(methylamino)butanoic acid, (3S)-3-amino-4-(3,3-Difluoropyrrolidine-1-yl)-4-oxobutanoic acid, (3S)-3-amino-4-[cyclopropyl(methyl)amino]-4-oxobutanoic acid, (3S)-3-amino-4-(2-azaspiro[3,3]heptan-2-yl)-4-oxobutanoic acid, (3S)-3-amino-4-(3-ethyl-3-fluoroazetidine-1-yl)-4-oxobutanoic acid, (3S)-3-amino-4-(3-fluoro-3-methylazetidine-1-yl)-4-oxobutanoic acid, (3S)-3-amino-4-(3-ethylazetidine-1-yl)-4-oxobutanoic acid, (3S)-3-amino-4-(3,3-dimethylazetidine-1-yl)-4-oxobutanoic acid, (3S)-3-amino-4-(diethylamino)-4-oxobutanoic acid.

[0149] In amino acids or their salts, the amino group and carboxyl group may be protected with protecting groups. Examples of protecting groups for the amino group include carbamate-type protecting groups, amide-type protecting groups, arylsulfonamide-type protecting groups, alkylamine-type protecting groups, and imide-type protecting groups. Specific examples of protecting groups for the amino group include Fmoc, Boc, Cbz, Alloc, trifluoroacetyl, pentafluoropropionyl, phthaloyl, tosyl, 2-nitrobenzenesulfonyl, 4-nitrobenzenesulfonyl, and 2,4-dinitrobenzenesulfonyl, with Fmoc being preferred among these. Examples of protecting groups for the carboxyl group include alkyl ester-type protecting groups, benzyl ester-type protecting groups, and substituted alkyl ester-type protecting groups. Specific examples of protecting groups for the carboxyl group include methyl, ethyl, t-Bu, benzyl, trityl, cumyl, methoxytrityl, 2-(trimethylsilyl)ethyl, 2,2,2-trichloroethyl, and allyl. Of these, t-Bu is preferred.

[0150] All references cited herein, including patent applications and publications, including the following, are incorporated herein by reference in their entirety: "Greene's, “ProtectiveGroupsin Organic Synthesis” (5th edition, JohnWiley & Sons 2014)."

[0151] The compounds described herein may, in certain embodiments, be salts thereof, preferably compounds or pharmaceutically acceptable salts thereof. In this specification, “compound or salt thereof” includes compounds and salts of compounds. Furthermore, in this specification, “compound or salt thereof” includes various solvates (including hydrates) and crystalline polymorphs.

[0152] Examples of compound salts include inorganic acid salts, organic acid salts, inorganic base salts, organic base salts, and acidic or basic amino acid salts.

[0153] Preferred examples of inorganic salts include hydrochloride, hydrobromide, sulfate, nitrate, and phosphate, while preferred examples of organic salts include acetate, succinate, fumarate, maleate, tartrate, citrate, lactate, stearate, benzoate, methanesulfonate, benzenesulfonate, and p-toluenesulfonate.

[0154] Preferred examples of inorganic base salts include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, aluminum salts, and ammonium salts. Preferred examples of organic base salts include diethylamine salt, diethanolamine salt, meglumine salt, and N,N-dibenzylethylenediamine salt.

[0155] Preferred examples of acidic amino acid salts include aspartate and glutamate, while preferred examples of basic amino acid salts include arginine salt, lysine salt, and ornithine salt. These salts can be produced, for example, by contacting a compound with an acid or a base.

[0156] In this specification, the structural formulas of compounds may represent certain isomers for convenience. However, unless otherwise specified, the present invention includes all geometric isomers, optical isomers based on chiral carbons, stereoisomers, tautomers, and other isomers and mixtures of isomers arising from the structure of a compound, and is not limited to the formulas shown for convenience. It may include either one isomer or a mixture. Therefore, unless otherwise specified, the compounds of the present invention may have an optically active form and a racemic form, both of which are included in the present invention and are not limited to these.

[0157] In some embodiments, the compounds described herein are isotope-labeled by substituting one or more atoms with atoms having the same atomic number (number of protons) but different mass numbers (sum of the number of protons and neutrons) in a ratio different from their natural abundance. Such isotope-labeled (e.g., radiolabeled) compounds described herein are included within the scope of the present invention. Isotopes included in the compounds herein include hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, and chlorine atoms, for example. ２ H, ３ H, １３ C, １４ C, １５ N, １７ O, １８ O, ３２ P, ３５ S, １８ F, ３６ This includes Cl, etc. The isotope-labeled compounds described herein are useful as therapeutic agents, prophylactic agents, research reagents (e.g., assay reagents), and diagnostic agents (e.g., in vivo imaging agents). The isotope-labeled compounds described herein can be prepared by methods similar to those for preparing unlabeled compounds, using reagents and solvents containing the corresponding isotope atoms.

[0158] The compounds according to the present invention may have crystalline polymorphisms, but are not particularly limited, and may consist of a single crystalline form or a mixture of crystalline forms.

[0159] The compounds according to the present invention include their prodrugs. A prodrug is a derivative of the compound of the present invention that has a group that can be chemically or metabolically degraded, and after administration to a living organism, is restored to the original compound to exhibit its original pharmacological effect, and includes complexes and salts that are not formed by covalent bonds.

[0160] <Chemical Synthesis Method of Peptide Compounds> The general method for producing the compounds of the present invention (which may hereinafter be referred to as "cyclic peptide compounds"), intermediate peptides, and unnatural amino acids is described below.

[0161] In this specification, an Fmoc amino acid is an amino acid in which the main chain amino group of the amino acid residue is protected by an Fmoc group, the side chain functional group of the amino acid residue is protected by a protecting group that is not cleaved in basic solutions, such as a t-Bu group, a THP group, or a Trt group, as exemplified by a piperidine-containing solution, as needed, and the main chain carboxyl group is unprotected.

[0162] Peptide synthesis methods that use Fmoc amino acids as the basic units for peptide chain elongation are called Fmoc methods. Peptide synthesis using the Fmoc method is achieved by elongating the aforementioned basic units at the N-terminus of the peptide until the desired sequence is reached.

[0163] In this specification, the basic unit of the extension reaction included in the Fmoc method is not particularly limited as long as it is a compound having an Fmoc-protected amino group and a carboxyl group. In addition to Fmoc amino acids, for example, dipeptides and tripeptides having an Fmoc-protected amino group and a carboxyl group may be used as the basic unit. A cyclic structure may be formed between the substituent of the nitrogen atom of the amino acid residue contained in the dipeptide or tripeptide, and / or the side chain of the amino acid residue.

[0164] The basic unit extended to the N-terminus may be something other than an Fmoc amino acid. The protecting group that replaces Fmoc may be, for example, a Boc amino acid with a Boc group, a Tfa amino acid with a Tfa group, or an Ns amino acid with an Ns group, or even a carboxylic acid analog that does not have an amino group.

[0165] <General Peptide Synthesis Methods> The peptide compounds used in this example and reference example can be synthesized by solid-phase synthesis. Examples of solid-phase synthesis methods include Amino Acids, 2018, 50, 39-68, or Solidphasepeptide synthesis (published by Bachem) [Accessed November 22, 2024], and the Internet. <URL:https: / / www.bachem.com / wp-admin / admin-ajax.php?juwpfisadmin=false&action=wpfd&task=file.download&wpfd_category_id=180&wpfd_file_id=213455&token=&preview=1> The following can be cited. In this embodiment and reference example, the peptide synthesis method by Fmoc described in International Publication No. 2013 / 100132 or International Publication No. 2018 / 225864 may be referenced. Peptide extension can be performed using the basic route shown in the following scheme (hereinafter sometimes referred to as the "basic peptide synthesis method"). That is, it comprises five steps: 1) starting with a material in which the carboxyl group of the Asp side chain or the carboxyl group of the peptide backbone is supported on 2-chlorotrityllesin, and a peptide extension reaction by Fmoc to the amino acid residue at the N-terminus; 2) a peptide cleavage reaction from the 2-chlorotrityllesin; 3) an amide cyclization reaction by condensation of the carboxyl group of the Asp side chain or the carboxyl group of the peptide backbone, which is released from the 2-chlorotrityllesin by the cleavage reaction, and the amino group at the N-terminus (triangular unit) of the peptide chain; 4) a deprotection reaction of the protecting group of the side chain functional group of the amino acid residue contained in the peptide chain, if necessary; and 5) purification of the compound by preparative HPLC. In these embodiments and reference examples, unless otherwise specified, cyclic peptides can be synthesized by the basic synthesis method for cyclic peptides shown in the following scheme.

[0166] The Fmoc method will be explained in more detail as an example. The main chain carboxyl group of an amino acid residue, or the side chain carboxyl group of an Fmoc amino acid in which the main chain carboxyl group of an amino acid residue is protected with an appropriate protecting group and the amino acid residue has a carboxyl group on its side chain, is supported on a solid phase by a chemical reaction with the functional group of the solid phase support. The resulting solid phase support is deprotected of the Fmoc group with a base such as piperidine or DBU, and the amino group produced by the deprotection reaction is condensed with the carboxyl group of the subsequently added basic unit Fmoc amino acid to form a peptide bond. In the condensation reaction, various combinations of carboxyl group activators are possible, such as a combination of DIC and HOBt, a combination of DIC and HOAt, and a combination of HATU and DIPEA. Instead of using an activator of the carboxyl group in the condensation reaction, an acid chloride of an amino acid can also be used. By repeating the deprotection reaction of the Fmoc group and the subsequent peptide bond formation reaction, a peptide compound with the desired amino acid sequence can be produced. After obtaining a peptide compound with the desired sequence, a cleavage reaction from the solid support and, if necessary, a deprotection reaction of the protecting groups contained in the peptide compound are performed. Structural transformation or cyclization reactions of the peptide compound can also be performed before the cleavage reaction from the solid support. The cleavage reaction from the solid support and the deprotection reaction may be carried out simultaneously under the same conditions, for example, 90:10 TFA / H2O. The cleavage reaction from the solid support and the deprotection reaction may also be carried out under separate conditions if necessary. For the cleavage reaction from the solid support, it may be possible to cleave the compound with a weak acid such as 1% TFA, or to utilize the orthogonality of the chemical reactions by using a protecting group that can be deprotected with a Pd-containing catalyst. During or at the end of these steps, steps such as cyclization of the obtained peptide compound can be carried out. For example, cyclization of the peptide compound can be performed by condensing the side chain carboxyl group of any amino acid residue contained in the peptide compound with the main chain amino group of the N-terminal amino acid residue of the peptide. Cyclization of peptide compounds can be performed by condensing the amino group of the side chain of any amino acid residue contained in the peptide compound with the carboxyl group of the main chain of the C-terminal amino acid residue of the peptide compound.

[0167] Peptide compounds can be cyclized by metathesis reactions by introducing olefins at two or more substituents on the side chains of amino acid residues and / or on the nitrogen atom of amino acid residues. Furthermore, the double bond formed by cyclization can be reduced to a single bond. In addition, a cyclopropane ring can be introduced by reacting the double bond site formed by cyclization of the peptide compound with diiodomethane-diethylzinc or the like. These cyclization reactions, reduction reactions, and cyclopropanation reactions may be carried out in the process of synthesizing basic units such as dipeptides and tripeptides that can be used as basic units for peptide chain extension reactions. Reaction orthogonality is required between the carboxyl group on the C-terminal side of the peptide compound that does not participate in the cyclization reaction and the carboxyl group on the side chain of the amino acid residue that does participate in the cyclization reaction. Reaction orthogonality is required between the amino group or hydroxyl group on the N-terminal main chain that does not participate in the cyclization reaction and the amino group on the side chain of the amino acid residue that does participate in the cyclization reaction. Reaction orthogonality is required between the olefin substituent on the side chain and / or nitrogen atom of the amino acid residue that does not participate in the cyclization reaction and the olefin that does participate in the cyclization reaction. The selection of protecting groups considering reaction orthogonality, and the desorption operations, can be carried out by referring to the methods described in, for example, "Greene's, 'Protective Groupsin Organic Synthesis' (5th edition, John Wiley & Sons 2014)." As a cyclization reaction of peptide compounds, cyclization can also be performed between the chloroacetyl group contained in the peptide compound and the thiol group of the cysteine ​​residue contained in the peptide compound. The reaction mixture thus obtained can be purified using a reversed-phase column or a molecular sieve column. These details are described in excellent manuals such as the "Solid-Phase Synthesis Handbook" published by Merck KGaA on May 1, 2002. Commercially available solid-phase supports can be used, with CTC resin, Wang resin, or SASRIN resin being examples. Resins used in such solid-phase synthesis are sometimes called solid-phase supports.

[0168] As an example of a general peptide synthesis method, the following describes a typical method for synthesizing a solid support carrying amino acids used in peptide synthesis using a peptide synthesizer.

[0169] The loading of Fmoc amino acids onto a solid support can be carried out by referring to the method described in International Publication No. 2013 / 100132 or International Publication No. 2018 / 225864. For example, 2-chlorotrityl chloride resin (CTC resin, about 3 g) and a solvent (e.g., anhydrous dichloromethane, about 20 mL) are placed in a reaction vessel (frit) with a filter, and the resin is allowed to swell. Next, the reaction mixture is filtered out of the reaction vessel to separate the resin, which is then added back to the reaction vessel. C-terminus-free Fmoc amino acid (a solution prepared by dissolving about 1 g of Fmoc amino acid in anhydrous methanol at 0.3 to 0.6 mol / L) and diisopropylethylamine (4 to 5 molar equivalents relative to the C-terminus-free Fmoc amino acid) are then added, and the reaction vessel is shaken for about 90 minutes. After removing the reaction mixture from the reaction vessel by filtration, the mixed solution of dehydrated methanol / diisopropylethylamine / dehydrated dichloromethane (approximately 3:1:10 volume ratio, approximately 22 mL) is added back to the reaction vessel and shaken for approximately 5 minutes. After removing the reaction mixture from the reaction vessel by filtration, the resin obtained by repeating the washing operation with dichloromethane (approximately 22 mL) five times is dried overnight under reduced pressure to obtain a resin supported with Fmoc amino acids. (In the formula, n represents an integer from 1 to 11, P １ ~P １１ Q １ ~Q １１ , R １ ~R １１ P as defined herein １ ~P １１ Q １ ~Q １１ , R １ ~R １１ These mean L １１ L as described herein １１ These represent the respective parts, and the circles represent the resin portion.

[0170] The above scheme shows how the Fmoc amino acid and the 2-chlorotrityl group attached to the resin are bonded to the carboxyl group of the Fmoc amino acid via an ester bond. The structure in which the 2-chlorotrityl group attached to the resin is bonded to the carboxyl group of the Fmoc amino acid via an ester bond is sometimes called a solid support on which the Fmoc amino acid is supported.

[0171] <Method for synthesizing cyclic compounds by cyclization of peptide compounds> A common example of peptide synthesis is the conversion of linear peptide compounds into cyclic peptides. This can be done by performing an intramolecular bond formation reaction, referring to methods described in books such as "Comprehensive Organic Transformations, A Guide to Functional Group Preparations, 3rd Edition, by R.C. Larock" or "March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 8th Edition, by MB Smith, J. March." A functional group transformation reaction can also be performed after the bond formation reaction. Examples of bond-forming reactions include C(O)-N bonds formed by the condensation of carboxyl and amino groups, COC bonds, C(O)-O bonds, and C(S)-O bonds utilizing oxygen atoms, C(O)-S bonds, C(S)-S bonds, CSSC bonds, CSC bonds, CS(O)-C bonds, and CS(O2)-C bonds utilizing sulfur atoms, and CNC bonds, C=NC bonds, NC(O)-N bonds, NC(S)N bonds, and C(S)-N bonds utilizing nitrogen atoms. Furthermore, examples include CC bond formation reactions catalyzed by transition metals, such as the Suzuki reaction, Heck reaction, Sonogashira reaction, and metathesis reaction. Examples of functional group transformation reactions that follow bond-forming reactions include oxidation reactions and reduction reactions. Specifically, examples include reactions that oxidize sulfur atoms to convert them into sulfoxides or sulfones. Also, examples include reduction reactions that reduce triple or double carbon-carbon bonds to convert them into double or single bonds.

[0172] When the carboxyl group on the main chain of the first amino acid and the amino group on the main chain of the second amino acid in a single peptide combine, a ring-closed structure is formed by peptide bonds, resulting in a cyclic peptide.

[0173] A cyclic peptide is obtained when a ring-closed structure is formed by covalent bonding between two different amino acids through methods such as the bonding of carboxyl groups and amino groups in the side chains of two different amino acids, the bonding of carboxyl groups in the side chains of two different amino acids to amino groups in the main chain, or the bonding of any two functional groups in two different amino acids.

[0174] In the following scheme, black circles or black squares represent amino acid residues, and linked black circles or black squares represent peptide chains linked by amide bonds. There are no particular restrictions on the number of amino acid residues that make up a peptide chain, and the number of amino acid residues is not limited to the number of black circles or black squares exemplified below.

[0175] <General method for producing cyclic peptide compounds 1> The cyclic portion of a cyclic peptide compound having a linear portion consists of an amino group at the N-terminus of the peptide compound and a carboxyl group at the C-terminus side chain (for example, in the case of aspartic acid and its derivatives (a compound in which the linear portion is bonded to the main chain carboxyl group of aspartic acid is exemplified in the scheme below), L is -CH ２ - and in the case of glutamic acid and its derivatives, L is -CH ２ CH ２ The compound (which is -) can be activated with an activating reagent, or converted to an activated ester, and then cyclized by an intramolecular condensation reaction to form a C(O)-N bond.

[0176] <General Method for Manufacturing Cyclic Peptide Compounds 2> The cyclic portion of a cyclic peptide compound in which the linear portion described in General Method for Manufacturing Cyclic Peptide Compounds 1 has become a C-Term consists of the amino group at the N-terminus of the peptide compound and the carboxyl group of the C-terminus side chain (for example, in the case of aspartic acid and its derivatives (a compound in which a C-Term is bonded to the main chain carboxyl group of aspartic acid is exemplified in the scheme below), L is -CH ２- and in the case of glutamic acid and its derivatives, L is -CH ２ CH ２ The compound (which is -) can be activated with an activating reagent or converted to an activated ester, and then cyclized by an intramolecular condensation reaction to form a C(O)-N bond.

[0177] The following shows a general method for producing peptide compounds by peptide modification. In the scheme below, Pn represents a substituent on a nitrogen atom, Rn and Qn represent amino acid side chains, black circles represent amino acid residues, linked black circles represent peptide chains linked by amide bonds, and m represents the number of amino acid residues and can take any integer value of 1 or more.

[0178] <Method 1 for introducing an alkyl group to the N-terminus nitrogen atom of a peptide compound supported on a solid phase support> Peptide compounds containing N-alkyl amino acids can be produced not only by using Fmoc-protected N-alkyl amino acids as starting materials and following the general peptide synthesis methods described herein, but also by alkylating the N-terminus nitrogen atom of a peptide compound supported on a solid phase support as shown below. Specifically, the nitrogen atom of the Tfa amide (trifluoroacetamide) at the N-terminus of a peptide compound supported on a solid phase support is reacted with an alkyl halide under basic conditions, and then treated with a reducing agent as described in Org. Lett., 2008, 10, 4815-4818, etc., to produce a peptide compound having the desired N-alkyl amino acid at the N-terminus. Furthermore, cyclic peptide compounds can be produced by peptide elongation, cleavage from the solid phase support, cyclization, deprotection, and purification according to the general peptide synthesis methods described herein. An example is shown in the scheme below. Rn and Qn represent the side chains of amino acids, Pn represents a hydrogen atom or alkyl group, and m represents any integer representing the number of amino acid residues.

[0179] <Method 2 for introducing an alkyl group to the N-terminal nitrogen atom of a peptide compound supported on a solid support> As an alternative method for introducing Pn to the N-terminal nitrogen, the method described in Nature Protocols, 2012, 7, 432-444 below can also be used. Specifically, an Ns group was introduced to the N-terminal amino group of a peptide compound supported on a solid support, and then Pn was introduced referring to Mitsunobu's method (Synthesis, 1981(1), 1-28). Subsequently, deprotection of the Ns group was performed to obtain a peptide having the desired Pn at the N-terminus. Furthermore, a cyclic peptide compound can be produced by peptide elongation, cleavage from the solid support, cyclization, deprotection, and purification according to the general peptide synthesis method described herein. An example is shown in the scheme below. Rn and Qn represent the side chains of amino acids, Pn represents hydrogen or an alkyl group, and m represents an arbitrary integer representing the number of amino acid residues.

[0180] <Method 3 for introducing an alkyl group to the N-terminal nitrogen atom of a peptide compound supported on a solid support> As an alternative method for introducing Pn to the N-terminal nitrogen, the following reductive amination reaction can be used. Specifically, the primary amino group at the N-terminus of a peptide compound supported on a solid support is subjected to any aldehyde (Pn'CHO, Pn is Pn'CH) by referring to the method of Borch et al. (J. Org. Chem. 1972, 37(10), 1673-1674). ２ A peptide having the desired Pn at the N-terminus can be obtained by treatment with Pn'COPn'' (where Pn is Pn'(Pn'')CH-) or any ketone. Furthermore, cyclic peptide compounds can be produced by peptide elongation, cleavage from solid support, cyclization, deprotection, and purification according to the general peptide synthesis methods described herein. An example is shown in the scheme below. Rn and Qn represent the side chains of amino acids, Pn represents hydrogen or alkyl group, and m represents any integer representing the number of amino acid residues.

[0181] <Method 1 for Producing Peptide Compounds Having an Aryl or Heteroaryl Group in the Side Chain> Peptides having an aryl or heteroaryl group in the side chain of an amino acid residue can be produced using an Fmoc amino acid having an aryl or heteroaryl group corresponding to the target compound in the side chain of the amino acid residue as a starting material, in addition to the general peptide synthesis method described herein. Alternatively, they can be produced using a peptide having a carboxyl group in the side chain of the amino acid residue as a precursor, as shown in the following method, by referring to the method of Huihui et al. (J. Am. Chem. Soc., 2016, 138(15), 5016-5019) or the method of Wadamoto (International Publication No. 2020 / 189540). Specifically, a peptide having a carboxyl group in the side chain of an amino acid residue can be activated with N-hydroxyphthalimide and reacted with any aryl halide or heteroaryl halide to produce a peptide having the desired aryl or heteroaryl group in the side chain of the amino acid residue. An example is shown in the scheme below.

[0182] <Method for producing peptide compounds containing an amide group in the side chain of an amino acid residue> In addition to the method of synthesizing peptide compounds having an amide group in the side chain of an amino acid residue using an Fmoc amino acid having the desired amide group in the side chain of the amino acid residue as a starting material, peptide compounds having a carboxyl group in the side chain of the amino acid residue as a precursor can also be synthesized by an amidation reaction using the peptide compounds having a carboxyl group in the side chain of the amino acid residue as shown below. Specifically, a peptide compound having a carboxyl group protected by a protecting group in the side chain of an amino acid residue is deprotected to synthesize a precursor having a carboxyl group in the side chain. Then, the precursor having a carboxyl group can be condensed with an arbitrary amine using a condensing agent as exemplified by HATU and DEPBT to produce the peptide compound having an amide group in the side chain of the desired side chain. An example is shown in the scheme below.

[0183] <Method for producing crosslinked peptide compounds by intramolecular coupling reaction of olefins> Using a peptide compound having olefins at two locations on the nitrogen atom substituent of an amino acid residue and / or on the side chain of an amino acid residue, a peptide compound in which two olefin sites of the peptide compound are crosslinked can be produced. Specifically, a peptide compound having olefins at two locations on the nitrogen atom substituent of an amino acid residue and / or on the side chain of an amino acid residue can be synthesized according to the general peptide synthesis method described herein, and then, referring to Nature Protocols, 2011, 6, 761-771, the two olefin sites can be crosslinked by an olefin metathesis reaction to produce a crosslinked peptide compound. Furthermore, by reducing the olefin at the crosslinking site by a hydrogenation reaction, a peptide compound crosslinked with saturated alkylene can be produced. An example is shown in the scheme below.

[0184] <General Method for Producing Non-Natural Amino Acids> The following is a general method for producing C-terminus-free non-natural amino acids in which the nitrogen atom of the amino acid is protected. In the following scheme, PG １ and PG １ ' is a protecting group for nitrogen atoms, PG ２ and PG ２ ' is a protecting group for the oxygen atom, PG ３ and PG ４ R is a protecting group for the side chain of an amino acid. ｎ and Q ｎ P is the side chain of an amino acid. ｎ P' is a substituent on the nitrogen atom, and P' is C １ -C ５Alkyl, R, R', R'', and R''' represent substituents on a hydrogen atom or an amino group, respectively. In the amino acid production methods shown below, chemical reactions may occur in functional groups other than the desired one. In such cases, the desired reaction can be controlled by introducing a protecting group to the unintended functional group. Examples of such protecting group desorption reactions include the method described in Greene's "Protective Groups in Organic Synthesis" (5th edition, John Wiley & Sons 2014). For functional group transformation reactions of compounds, refer to Larock's "Comprehensive Organic Transformations: A Guide to Functional Group Preparations" (5th edition) and Smith's "March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure" (8th edition).

[0185] <Method 1 for producing amino acids by protecting group removal reaction> Protecting group (PG) attached to the nitrogen atom of the amino acid １ Non-natural amino acids having a protecting group (PG) can be produced by the following method: By introducing a protecting group to an N-terminal free amino acid available from a commercial supplier and, if necessary, deprotecting it according to a standard procedure, the nitrogen atom of the target amino acid can be fitted with a protecting group (PG). １ This allows for the production of C-terminus-free non-natural amino acids with the following properties. An example scheme is shown below.

[0186] <Method for producing amino acids by the removal of protecting groups, part 2> A protecting group (PG) is attached to the nitrogen atom of the amino acid. １ Non-natural amino acids with a ') can be produced by the following method: A protecting group (PG) at the N-terminus, available from commercial suppliers. １ By performing a deprotection reaction and a protecting group introduction reaction on an amino acid that has a protecting group (PG) using a standard method, a protecting group (PG) can be attached to the nitrogen atom of the target amino acid. １ It is possible to produce C-terminus-free non-natural amino acids with the ') symbol. An example scheme is shown below.

[0187] <Method for producing N-substituted amino acids by ring-opening reaction of the oxazolidinone ring> Add -CH to the nitrogen atom of the amino acid ２ Unnatural amino acids to which a group represented by -P' has been introduced can be produced by the method shown in the following scheme. By treating a C-terminus-free amino acid available from commercial suppliers with an aldehyde, referring to the method of Freidinger et al. (J. Org. Chem., 1983, 48(1), 77-81), an oxazolidinone compound to which a cyclic protecting group has been introduced can be obtained. Subsequently, by performing a ring-opening reaction of the oxazolidinone ring, the desired C-terminus-free unnatural amino acid can be produced. An example is shown in the scheme below.

[0188] <Method for producing N-substituted amino acids using electrophiles> The nitrogen atom of the amino acid is replaced with P ｎ Non-natural amino acids into which the group has been introduced can be produced by the method shown in the following scheme: Commercially available C-terminus-free amino acids are subjected to electrophilic reactions (P) in the presence of a base. ｎ By applying -X) P ｎ A group can be introduced. Examples of electrophiles include alkylating agents, alkenylating agents, alkynylating agents, or aralkylating agents. Of the introduced Pn, alkenyl and alkynyl groups can be converted to the corresponding alkyl groups by appropriate reduction reactions. Then, by deprotecting the C-terminal protecting group, the desired C-terminus-free unnatural amino acid can be produced. An example is shown in the scheme below.

[0189] <Method 1 for Producing Amino Acids Having an Aryl or Heteroaryl Group in the Side Chain> Unnatural amino acids in which an aryl group or a heteroaryl group (hereinafter referred to as "Ar" in the scheme) is introduced into the side chain of the amino acid can be produced by the method shown in the scheme below. An NHPI group can be introduced into the side chain by reacting the carboxyl group of a protected amino acid (n is 1 or 2, and Pn is H or an alkyl group) with N-hydroxyphthalimide (NHPI). Referring to the method of Huihui et al. (J. Am. Chem. Soc., 2016, 138(15), 5016-5019) or the method of Wadamoto (International Publication No. 2020 / 189540), an unnatural amino acid containing an aralkyl group or a heteroaralkyl group in the side chain, in which an aryl group or heteroaryl group has been introduced, can be produced by reacting with an aryl halide or a heteroaryl halide. Subsequently, a C-terminus-free unnatural amino acid can be produced by deprotecting the protecting group at the C-terminus. An example of the scheme is shown below.

[0190] <Method for producing amino acids having ether bonds in the side chain 2> An alkoxy group or an aralkoxy group (R) which may be substituted in the side chain of the amino acid ｂ Non-natural amino acids having O) can be produced by the method shown in the following scheme: A commercially available cyclic compound (where n is 1 or 2) is subjected to BF according to a standard method. ３ ・OET ２ In the presence of a Lewis acid such as, a suitable alcohol (R ｂ By ring-opening with OH), serine ether compounds can be obtained. The obtained serine ether compounds can then be used to produce the desired C-terminus-free unnatural amino acids by appropriately removing protecting groups as needed. An example scheme is shown below.

[0191] <Method for producing amino acids having ether links in the side chain 3> An alkoxy group, aralkoxy group, cycloalkoxy group, or heterocyclylalkoxy group (-OR) which may be substituted in the side chain of the amino acid ｂNon-natural amino acids having ) can be produced by the method shown in the following scheme: Commercially available serine derivatives (where n is 1 or 2 and Pn is H or an alkyl group) or hydroxy compounds derived therefrom are prepared in the presence of an electrophile (R) in the presence of a suitable base, referring to Williamson's method (Liebigs Ann. Chem. 1851, 77, 37-49). ｂ By reacting with -X), a serine ether compound can be obtained. ｂ If it has further convertible functional groups, R can be further converted by performing additional functional group transformations. ｂ It can be converted into the desired functional group. Examples of additional functional group conversions include reduction reactions of multiple bonds. Serine ether compounds have a protecting group on the nitrogen atom (PG １ By detoxifying a protecting group, including converting the original protecting group to another protecting group, the desired C-terminus-free non-natural amino acid can be produced. An example scheme is shown below.

[0192] <Method for producing amino acids having ether bonds in the side chain 4> An alkoxy group or an aralkoxy group (-OR) which may be substituted in the side chain of the amino acid ｂ Non-natural amino acids having a cyclic protecting group, and further having a group introduced to the nitrogen atom of the amino acid, can be produced by the method shown in the following scheme. By reacting a commercially available serine ether compound, or a serine ether compound produced by the method described above (where n is 1 or 2), with an aldehyde according to the method of Freidinger et al. (J. Org. Chem., 1983, 48(1), 77-81), an oxazolidinone compound with a cyclic protecting group can be obtained. Then, by performing a ring-opening reaction of the oxazolidinone ring, the desired C-terminus-free non-natural amino acid can be produced. An example is shown in the scheme below.

[0193] <Method 1 for producing unnatural amino acids with carboxyl groups in the side chain> Unnatural amino acids with carboxyl groups in the side chain can be produced by the method shown in the following scheme. Available from commercial suppliers, the carboxyl group in the side chain is PG ３The main chain carboxyl group of the starting material protected by (n is 1 or 2, and Pn is H or an alkyl group) can be converted to an amide group by condensing an amine (R''R'''NH) in the presence of a coupling agent such as DIC. Then PG ３ By performing the deprotection reaction, unnatural amino acids with a carboxyl group in the desired side chain can be produced. An example scheme is shown below.

[0194] <Method for producing unnatural amino acids having an aminocarbonylalkoxy group in the side chain> Unnatural amino acids having an aminocarbonylalkoxy group in the side chain (where n is 1 or 2 and Pn is H or an alkyl group) can be produced by the following scheme: Using a starting material with a hydroxyl group in the side chain, which is available from a commercial supplier, chloroacetyl chloride and amine (R-NH ２ By treating the chloroacetyl compound obtained from ) with the desired unnatural amino acid having an aminocarbonylalkoxy group in its side chain, a protecting group on the nitrogen atom can be added as needed. １ From PG ２ It can also be converted to this. For information on how to attach and detach the protecting group, please refer to "Greene's, 'ProtectiveGroupsin Organic Synthesis' (5th edition, JohnWiley & Sons 2014)". An example is shown in the scheme below.

[0195] <Method for producing unnatural amino acids with cycloalkylidene alkyl groups in the side chain> Unnatural amino acids with cycloalkylidene alkyl groups introduced into the side chain can be produced by the following scheme. PG can be synthesized from starting materials available from commercial suppliers. １ By performing a metathesis reaction between the alkenyl group of a starting material protected by a cycloalkyl group (where n is 1 or 2, Pn is H or an alkyl group, and Cy is a cycloalkyl ring) and a cycloalkenyl compound in the presence of a metal catalyst, such as a Grubbs catalyst, unnatural amino acids with a cycloalkylidene alkyl group introduced into the desired side chain can be produced. An example scheme is shown below.

[0196] In the production of the compounds of the present invention represented by formulas (1) to (4) above, the raw material compounds and various reagents may form salts or solvates (including hydrates), and these will vary depending on the starting materials, solvents used, etc., and are not particularly limited as long as they do not inhibit the reaction.

[0197] The solvent used will vary depending on the starting materials, reagents, etc., and it goes without saying that it is not particularly limited as long as it does not inhibit the reaction and dissolves the starting materials to some extent.

[0198] Various isomers (e.g., geometric isomers, optical isomers based on chiral carbon, rotational isomers, stereoisomers, tautomers, etc.) can be purified and isolated using conventional separation methods such as recrystallization, diastereomerization, enzymatic resolution, and various chromatography techniques (e.g., thin-layer chromatography, column chromatography, high-performance liquid chromatography, gas chromatography, etc.).

[0199] If the compound according to the present invention is obtained as a free form, it can be converted to a salt or solvate (including hydrate) thereof, which may be formed by the compound, according to conventional methods.

[0200] The isolation and purification of the compounds according to the present invention can be carried out by applying conventional chemical operations such as extraction, concentration, distillation, crystallization, filtration, recrystallization, and various types of chromatography.

[0201] <Pharmaceutical Composition> The present invention provides a pharmaceutical composition containing the compound of the present invention. The pharmaceutical composition of the present invention can be formulated by introducing a pharmaceutically acceptable carrier in addition to the compound of the present invention or a salt thereof, using known methods. For formulation, commonly used excipients, binders, lubricants, colorants, flavoring agents, and, if necessary, stabilizers, emulsifiers, absorption enhancers, surfactants, pH adjusters, preservatives, antioxidants, etc., can be used, and the formulation is carried out by conventional methods by combining components that are generally used as raw materials for pharmaceutical preparations. For example, to produce an oral preparation, the compound of the present invention or a salt thereof and an excipient, and further, if necessary, binders, disintegrants, lubricants, colorants, flavoring agents, etc., are added, and then the preparation is carried out by conventional methods to form a powder, fine granules, granules, tablets, coated tablets, capsules, etc.

[0202] These tablets and granules may, of course, be coated with sugar or other coatings as needed. Furthermore, when manufacturing liquid preparations such as syrups and injectable preparations, the compound according to the present invention or a pharmaceutically acceptable salt thereof may be compounded by conventional methods by adding pH adjusters, solvents, isotonic agents, and, if necessary, solubilizers and stabilizers.

[0203] For example, it can be used parenterally in the form of a sterile solution or suspension in water or other pharmaceutically acceptable liquid for injection. For example, it can be formulated by mixing it with a pharmacologically acceptable carrier or medium, specifically sterile water, saline solution, vegetable oil, emulsifier, suspension agent, surfactant, stabilizer, flavoring agent, excipient, vehicle, preservative, binder, etc., in a unit dose form generally required for pharmaceutical practice. Sterile compositions for injection can be formulated using a vehicle such as distilled water for injection, following standard pharmaceutical practice procedures.

[0204] Administration is preferably by oral administration, but the method of administration is not limited to oral administration. Parenteral administration methods include, specifically, injectable, nasal, pulmonary, and transdermal formulations. Examples of injectable formulations include systemic or local administration by intravenous, intramuscular, intraperitoneal, or subcutaneous injection.

[0205] Furthermore, the administration method can be appropriately selected depending on the patient's age and symptoms. For example, the dosage of the pharmaceutical composition containing the peptide compound produced by the method of the present invention can be selected within the range of 0.0001 mg to 1000 mg per kg of body weight per dose. Alternatively, the dosage can be selected within the range of 0.001 mg / body to 100,000 mg / body per patient, but is not necessarily limited to these values. The dosage and administration method will vary depending on the patient's weight, age, symptoms, etc., but a person skilled in the art can appropriately select them.

[0206] In one embodiment, the compound or a salt thereof of the present invention, or the compound thereof, can bind to ALK in a target. The compound or a salt thereof of the present invention, or a pharmaceutical composition containing the compound or a salt thereof of the present invention, can be used to inhibit ALK.

[0207] In one embodiment, the compound or salt of the present invention can bind to ALK in a target and can be used in the manufacture of a pharmaceutical for inhibiting ALK.

[0208] In one embodiment, the present invention relates to a method for conjugating a compound of the present invention to ALK in a subject, or a method for inhibiting ALK in a subject, comprising administering an effective amount of the compound of the present invention or a salt thereof to a subject in need thereof.

[0209] In one embodiment, the compound or a salt thereof of the present invention, or a pharmaceutical composition comprising the compound or a salt thereof of the present invention, can be used to treat and / or prevent cancer in a subject.

[0210] In one embodiment, the compounds of the present invention or salts thereof can be used in the manufacture of pharmaceuticals for treating and / or preventing cancer in a subject.

[0211] In one embodiment, the present invention relates to a method for treating and / or preventing cancer in a subject, comprising administering an effective amount of the compound of the present invention or a salt thereof to a subject in need thereof.

[0212] Preferably, the cancer is one having an ALK gene abnormality, more preferably one being positive for an ALK fusion gene, and specifically, lymphoma is one example.

[0213] In this specification, "subjects" include mammals, and among mammals, humans are preferred.

[0214] The compounds disclosed herein may be used alone or in combination with other agents. In one aspect, the modes and methods of use described above may further include the step of administering an effective amount of at least one additional therapeutic agent to the subject. For example, the compounds disclosed herein may be administered simultaneously with at least one additional therapeutic agent.

[0215] The combination therapies described above include combined administration (two or more therapeutic agents contained in the same or separate formulations) and individual administration, in which case the compound disclosed herein may be administered prior to, simultaneously with, and / or subsequently to the administration of an additional therapeutic agent. In one embodiment, the administration of the compound disclosed herein and the administration of an additional therapeutic agent are performed within about one month, or within about one, two, or three weeks, or within about one, two, three, four, five, or six days. The compounds disclosed herein may also be used in combination with radiotherapy.

[0216] The compounds disclosed herein can be used in combination with ALK inhibitors. Preferred ALK inhibitors are ALK tyrosine kinase inhibitors (ALK-TKIs), and more preferably, compounds selected from the group consisting of crizotinib, ceritinib, alectinib (more preferably alectinib hydrochloride), brigatinib, lorlatinib, ensartinib, repotrectinib, entrectinib, TPX-0131, and NVL-655, or salts thereof, are preferred, but are not limited to these.

[0217] The compounds disclosed herein also demonstrate efficacy against cancers with ALK-TKI resistance mutations. Cancers with ALK-TKI resistance mutations include, but are not limited to, cancers with secondary mutations in the ALK kinase domain such as L1196M, G1269A, C1156Y, F1174L, G1202R, and I1171T mutations, and combinations thereof (e.g., L1196M / G1202R mutation).

[0218] Furthermore, all prior art documents cited herein are incorporated herein by reference.

[0219] The present invention will be further illustrated by the following examples, but the present invention is not limited thereto. All starting materials and reagents were obtained from commercial suppliers or synthesized using known methods. The LC / MS analytical conditions used in these examples are shown in Table 1.

[0220]

[0221] Example 1. Amino acids and resins used in peptide synthesis using a peptide synthesizer. The peptide synthesis described herein used the amino acids and amino acid-supported resins listed in Tables 2, 3, 4, 5, and 6.

[0222] Example 1-1. Fmoc-amino acids used: The Fmoc-amino acids listed in Table 2 were purchased from a commercial supplier.

[0223]

[0224] The Fmoc-amino acids listed in Table 3 were purchased from commercial suppliers. While CAS numbers were not issued for the Fmoc-amino acids listed in Table 3 at the time of filing this invention, they can be obtained, for example, by deprotecting and protecting functional groups from Boc-amino acids or unprotected amino acids for which CAS numbers have been issued. For methods of deprotection and protection, see, for example, T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis (5th edition, John Wiley & Sons 2014).

[0225]

[0226] Examples 1-2. Synthesis of Fmoc-amino acids known from literature. The Fmoc-amino acids listed in Table 4 were synthesized according to the methods described in the following literature.

[0227]

[0228] Examples 1-3. Synthesis of Novel Fmoc-Amino Acids The Fmoc-amino acids listed in Table 5 were synthesized according to the scheme shown below.

[0229]

[0230] Synthesis of compound aa4-001 (Fmoc-MeSer(iPr)-OH)

[0231] Compound aa4-001-a (2.50 g, 6.77 mmol, CAS number: 2137146-08-6), DCM (67.7 mL), magnesium sulfate (2.04 g, 16.9 mmol), and paraformaldehyde (0.610 g, 20.3 mmol) were added to the reaction vessel. A boron trifluoride diethyl ether complex (BF) was added to the resulting reaction mixture. ３ ・OET ２(1.03 mL, 8.12 mmol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. The reaction mixture was passed through a silica gel pad, the silica gel pad was washed with DCM, and the combined filtrate was concentrated under reduced pressure to obtain compound aa4-001-b as the crude product. DCM (67.6 mL), TES (2.69 mL, 16.9 mmol), and water (0.122 mL, 6.76 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-001-b. BF was added to the resulting reaction mixture. ３ ・OET ２ (1.29 mL, 10.2 mmol) was added dropwise, and the mixture was stirred at room temperature for 3 hours. TES (0.539 mL, 3.38 mmol) was added to the resulting reaction mixture, and BF ３ ・OET ２ (0.429 mL, 3.38 mmol) was added dropwise, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (10 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in acetonitrile (20 v / w), washed three times with n-hexane (10 v / w), and then the acetonitrile layer was concentrated under reduced pressure. Acetonitrile and water were added to the obtained residue, and after freeze-drying, compound aa4-001 was obtained as a colorless oily substance in the form of 2.35 g (yield 91%, 2 steps). LCMS (ESI) m / z = 384.4 [M + H] ＋ Retention time: 0.85 minutes (Analysis conditions: SQDFA-01)

[0232] Synthesis of compound aa4-002 (Fmoc-MeAbu(cHep)-OH)

[0233] Compound aa4-002-a (1.00 g, 2.37 mmol, CAS number: 2349977-16-6) was used as the starting material, and the crude product of compound aa4-002-b was obtained by the same method as the synthesis of compound aa4-001-b. DCM (7.90 mL), TES (0.944 mL, 5.93 mmol), and water (0.043 mL, 2.37 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-002-b. The resulting reaction mixture was subjected to BF under ice cooling. ３ ・OET ２ (0.451 mL, 3.56 mmol) was added dropwise, and the mixture was stirred at room temperature for 3.5 hours. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (5 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in acetonitrile (20 v / w), washed three times with n-hexane (10 v / w), and then the acetonitrile layer was concentrated under reduced pressure. Acetonitrile and water were added to the obtained residue, and after freeze-drying, 0.936 g of compound aa4-002 was obtained as a white solid (91% yield, 2 steps). LCMS (ESI) m / z = 436.3 [M + H] ＋ Retention time: 0.73 minutes (Analysis conditions: SQDFA-02)

[0234] Synthesis of compound aa4-003 (Fmoc-MeAbu(4-(1-Me-cPr))-OH)

[0235] Compound aa4-003-a (1.90 g, 5.01 mmol, CAS number: 2349818-15-9) was used as the starting material, and the crude product of compound aa4-003-b was obtained by the same method as the synthesis of compound aa4-001-b. DCM (47.3 mL), TES (1.88 mL, 11.8 mmol), and water (0.085 mL, 4.73 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-003-b. BF was added to the resulting reaction mixture. ３ ・OET ２(0.898 mL, 7.09 mmol) was added dropwise, and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (10 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The obtained residue was added to 5% sodium carbonate aqueous solution (20 v / w) and washed twice with TBME / n-hexane (1 / 1, 20 v / w). Phosphoric acid was added to the aqueous layer to adjust the pH to 3-4, and then extracted twice with TBME (20 v / w). The obtained organic layer was washed with saturated saline solution (10 v / w) and dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. Acetonitrile and water were added to the obtained residue, and after freeze-drying, 0.860 g of compound aa4-003 was obtained as a white solid (yield 44%, 2 steps). LCMS (ESI) m / z = 394.2 [M+H] ＋ Retention time: 0.53 minutes (Analysis conditions: SQDFA-02)

[0236] Synthesis of compound aa4-004 (Fmoc-MeaThr(Et)-OH)

[0237] Compound aa4-004-a (5.00 g, 13.5 mmol, CAS number: 1279034-29-5) was used as the starting material, and the crude product of compound aa4-004-b was obtained by the same method as the synthesis of compound aa4-001-b. DCM (135 mL), TES (5.40 mL, 33.8 mmol), and water (0.244 mL, 13.5 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-004-b. BF was added to the resulting reaction mixture. ３ ・OET ２ (2.54 mL, 20.3 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. TES (5.40 mL, 33.8 mmol) was added to the resulting reaction mixture, and BF ３ ・OET ２(2.54 mL, 20.3 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (10 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography (0.1% FA aqueous solution / 0.1% FA acetonitrile solution) to obtain 2.82 g of compound aa4-004 as a white solid (yield 54%, 2 steps). LCMS (ESI) m / z = 384.3 [M+H] ＋ Retention time: 0.98 minutes (Analysis conditions: SQDFA-01)

[0238] Synthesis of compound aa4-005 (Fmoc-MeChg(4-F2)-OH)

[0239] Compound aa4-005-a (3.00 g, 7.22 mmol, CAS number: 2248184-59-8) was used as the starting material, and the crude product of compound aa4-005-b was obtained by the same method as the synthesis of compound aa4-001-b. DCM (72.3 mL), TES (2.88 mL, 18.1 mmol), and water (0.130 mL, 7.23 mmol) were added to the reaction vessel containing the obtained crude product of compound aa4-005-b. BF was added to the resulting reaction mixture. ３ ・OET ２ (1.37 mL, 10.8 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. TES (2.88 mL, 18.1 mmol) was added to the resulting reaction mixture, and BF ３ ・OET ２ (1.37 mL, 10.8 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. To the resulting reaction mixture, TES (2.88 mL, 18.1 mmol) and water (0.065 mL, 3.61 mmol) were added, and BF was added. ３ ・OET ２(1.37 mL, 10.8 mmol) was added dropwise, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (10 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (20 v / w), washed three times with n-hexane (10 v / w), and then the acetonitrile layer was concentrated under reduced pressure. TBME (15 v / w) was added to the resulting residue, and it was extracted twice with 3.5% potassium bicarbonate aqueous solution (10 v / w). Phosphoric acid was added to the aqueous layer to adjust the pH to 3-4, then extracted with TBME (15 v / w), and the resulting organic layer was washed with saturated saline solution (10 v / w) and dried over sodium sulfate. After filtering off the desiccant, the filtrate was concentrated under reduced pressure to obtain 2.34 g of compound aa4-005 as a white solid (75% yield, 2 steps). LC-MS (ESI) m / z = 430.3 [M+H] ＋ Retention time: 0.87 minutes (Analysis conditions: SQDFA-01)

[0240] Synthesis of compound aa4-006 (Fmoc-MeGly(4-THP)-OH)

[0241] Compound aa4-006-a (2.12 g, 5.56 mmol, CAS number: 368866-31-3) was used as the starting material, and the crude product of compound aa4-006-b was obtained by the same method as the synthesis of compound aa4-001-b. DCM (15.0 mL), TES (2.66 mL, 16.7 mmol), and water (0.100 mL, 5.56 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-006-b. BF was added to the resulting reaction mixture. ３ ・OET ２(1.41 mL, 11.1 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. Water / saturated ammonium chloride aqueous solution (1 / 1, 5.0 mL) and water (2.0 mL) were added to the reaction mixture, and the mixture was stirred at room temperature for 10 minutes. The mixture was then concentrated under reduced pressure, and the DCM was removed by distillation. The solid was collected by filtration, washed with water and n-hexane, and dried under reduced pressure to obtain 1.32 g of compound aa4-006 as a white solid (60% yield, 2 steps). LCMS (ESI) m / z = 396.3 [M + H] ＋ Retention time: 0.74 minutes (Analysis conditions: SQDFA-01)

[0242] Synthesis of compound aa4-007 (Fmoc-MeGly(cBu-3-F2)-OH)

[0243] Compound aa4-007-a (3.00 g, 7.74 mmol, CAS number: 2349734-08-1) was used as the starting material, and the crude product of compound aa4-007-b was obtained by the same method as the synthesis of compound aa4-001-b. DCM (77.0 mL), TES (3.08 mL, 19.3 mmol), and water (0.139 mL, 7.74 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-007-b. BF was added to the resulting reaction mixture. ３ ・OET ２ (1.47 mL, 11.6 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. To the resulting reaction mixture, TES (3.08 mL, 19.3 mmol) and water (0.070 mL, 3.87 mmol) were added, and BF was added. ３ ・OET ２(1.47 mL, 11.6 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (10 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. TBME (20 v / w) was added to the resulting residue, and it was extracted twice with 3.5% potassium bicarbonate aqueous solution (10 v / w). Phosphoric acid was added to the aqueous layer to adjust the pH to 3-4, and then extracted with DCM (20 v / w). The resulting organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain 2.48 g of compound aa4-007 as a white solid (80% yield, 2 steps). LCMS (ESI) m / z = 402.5 [M+H] ＋ Retention time: 0.84 minutes (Analysis conditions: SQDFA-01)

[0244] Synthesis of compound aa4-008 (Fmoc-MeGly(cHep)-OH)

[0245] Compound aa4-008-a (5.00 g, 12.7 mmol, CAS number: 2304413-61-2) was used as the starting material, and the crude product of compound aa4-008-b was obtained by the same method as the synthesis of compound aa4-001-b. DCM (31.8 mL), TES (5.07 mL, 31.8 mmol), and water (0.229 mL, 12.7 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-008-b. BF was added to the resulting reaction mixture. ３ ・OET ２ (2.39 mL, 19.1 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. To the resulting reaction mixture, TES (1.68 mL, 10.5 mmol) and water (0.076 mL, 4.19 mmol) were added, and BF was added. ３ ・OET ２(0.796 mL, 6.35 mmol) was added dropwise, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (10 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was mixed with 3.5% potassium bicarbonate aqueous solution (30 v / w) and washed sequentially with TBME (5 v / w), n-hexane (8 v / w), and toluene / n-hexane (1 / 9, 10 v / w). Phosphoric acid was added to the aqueous layer to adjust the pH to 3-4, then extracted with TBME (10 v / w), and the resulting organic layer was washed with saturated saline solution (10 v / w) and then dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. Acetonitrile and water were added to the resulting residue, and after freeze-drying, 3.59 g of compound aa4-008 was obtained as a white solid (69% yield, 2 steps). LC-MS (ESI) m / z = 408.4 [M + H] ＋ Retention time: 0.74 minutes (Analysis conditions: SQDFA-02)

[0246] Synthesis of compound aa4-009 (Fmoc-MeSe(iBu)-OH)

[0247] Compound aa4-009-a (250 g, 0.652 mol, CAS number: 1607004-16-9), DCM (4.25 L), magnesium sulfate (196 g, 1.63 mol), and paraformaldehyde (58.7 g, 1.96 mol) were added to the reaction vessel. BF was added to the resulting reaction mixture. ３ ・OET ２ (99.1 mL, 0.782 mol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. After filtering off the solid, the solid was washed with DCM (0.500 L), and the washing solution was combined with the solid to obtain a DCM solution of compound aa4-009-b. To the obtained DCM solution of compound aa4-009-b, TES (260 mL, 1.63 mol) and water (11.7 mL, 0.652 mol) were added. The reaction mixture obtained under ice cooling was then treated with BF ３ ・OET ２(124 mL, 0.978 mol) was added dropwise, and the mixture was stirred at room temperature for 5 hours. Saturated ammonium chloride aqueous solution (10 v / w) was added to the reaction mixture, and the resulting organic layer was sequentially washed with saturated ammonium chloride aqueous solution (5 v / w) and saturated brine (5 v / w), and then concentrated under reduced pressure. TBME (10 v / w) and n-heptane (10 v / w) were added to the resulting residue, and the mixture was stirred at room temperature for 15 minutes. Then, 3.5% potassium bicarbonate aqueous solution (10 v / w) and acetonitrile (5 v / w) were added, and the mixture was stirred at room temperature for 15 minutes. The resulting aqueous layer was washed twice with TBME / n-hexane (1 / 1, 10 v / w). Under ice cooling, 2 M hydrochloric acid solution was added to the aqueous layer to adjust the pH to 2-3, and then the mixture was extracted twice with TBME (10 v / w). The obtained organic layer was concentrated under reduced pressure, the resulting residue was dissolved in DCM (2 v / w) and passed through a silica gel pad, the silica gel pad was washed with DCM / methanol (20 / 1), and the combined filtrate was concentrated under reduced pressure to obtain 223 g of compound aa4-009 as a white solid (yield 86%, 2 steps). LCMS (ESI) m / z = 398.6 [M+H] ＋ Retention time: 0.90 minutes (Analysis conditions: SQDFA-01)

[0248] Synthesis of compound aa4-010 (Fmoc-MeSer(cPent)-OH)

[0249] Compound aa4-010-a (9.40 g, 23.8 mmol, CAS number: 2382243-79-8), DCM (60.0 mL), magnesium sulfate (7.15 g, 59.4 mmol), and paraformaldehyde (2.14 g, 71.3 mmol) were added to the reaction vessel. BF was added to the resulting reaction mixture. ３ ・OET ２(3.61 mL, 28.5 mmol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. After filtering off the solid, the filtrate was concentrated under reduced pressure. Ethyl acetate (16 v / w) was added to the resulting residue, and the mixture was washed twice with saturated sodium bicarbonate aqueous solution (16 v / w) and then sequentially with saturated brine (10 v / w). The organic layer was then dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain compound aa4-010-b as the crude product. DCM (79.0 mL), TES (9.47 mL, 59.5 mmol), and water (0.428 mL, 23.8 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-010-b. The resulting reaction mixture was fermented under ice cooling with BF ３ ・OET ２ (4.52 mL, 35.7 mmol) was added dropwise, and the mixture was stirred at room temperature for 2 hours. To the resulting reaction mixture, TES (0.947 mL, 5.95 mmol) and water (0.043 mL, 2.38 mmol) were added, and BF was added. ３ ・OET ２ (0.452 mL, 3.57 mmol) was added dropwise, and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (5 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in acetonitrile (20 v / w), washed three times with n-hexane (10 v / w), and then the acetonitrile layer was concentrated under reduced pressure. Acetonitrile and water were added to the obtained residue, and after freeze-drying, 9.45 g of compound aa4-010 was obtained as a white solid (97% yield, 2 steps). LCMS (ESI) m / z = 410.2 [M + H] ＋ Retention time: 0.93 minutes (Analysis conditions: SQDFA-01)

[0250] Synthesis of compound aa4-011 (Fmoc-MeAbu(cPent)-OH)

[0251] Using compound aa4-011-a (8.76 g, 22.3 mmol, CAS number: 2349655-85-0) as a starting material, the crude product of compound aa4-011-b was obtained by the same method as the synthesis of compound aa4-010-b. Using the obtained crude product of compound aa4-011-b as a starting material, 8.31 g of compound aa4-011 was obtained as a white solid (yield 92%, 2 steps) by the same method as the synthesis of compound aa4-010. LCMS (ESI) m / z = 408.3 [M + H] ＋ Retention time: 0.60 minutes (Analysis conditions: SQDFA-02)

[0252] Synthesis of compound aa4-012 (Fmoc-MeAbu(tBu)-OH)

[0253] Compound aa4-012-a (3.50 g, 9.17 mmol, CAS number: 1217704-60-3), DCM (45.0 mL), magnesium sulfate (2.76 g, 22.9 mmol), and paraformaldehyde (0.826 g, 27.5 mmol) were added to the reaction vessel. BF was added to the resulting reaction mixture. ３ ・OET ２ (1.40 mL, 11.0 mmol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. After filtering off the solid, a DCM solution of compound aa4-012-b was obtained. To the obtained DCM solution of compound aa4-012-b, TES (3.65 mL, 22.9 mmol) and water (0.165 mL, 9.17 mmol) were added. The resulting reaction mixture was subjected to BF under ice cooling. ３ ・OET ２ (1.74 mL, 13.8 mmol) was added dropwise, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was sequentially washed with saturated ammonium chloride aqueous solution and saturated saline solution, and the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (150 mL), washed three times with n-hexane (100 mL), and the acetonitrile layer was concentrated under reduced pressure to obtain 3.63 g of compound aa4-012 as a white solid (100% yield, 2 steps). LCMS (ESI) m / z = 396.1 [M + H] ＋Retention time: 0.98 minutes (Analysis conditions: SQDFA-01)

[0254] Synthesis of compound aa4-013 (Fmoc-MeHph(3-I)-OH)

[0255] Compound aa4-013-a (14.4 g, 27.3 mmol, CAS number: 2349317-02-6), DCM (100 mL), magnesium sulfate (8.22 g, 68.3 mmol), and paraformaldehyde (2.46 g, 81.9 mmol) were added to the reaction vessel. BF was added to the resulting reaction mixture. ３ ・OET ２ (3.46 mL, 27.3 mmol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 7 hours. After filtering off the solid, the solid was washed with DCM (30 mL), and the washing solution was combined with the solid to obtain a DCM solution of compound aa4-013-b. To the obtained DCM solution of compound aa4-013-b, TES (8.70 mL, 54.6 mmol) and water (0.492 mL, 27.3 mmol) were added. BF was added to the resulting reaction mixture. ３ ・OET ２ (3.46 mL, 27.3 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. TES (2.18 mL, 13.7 mmol) and water (0.123 mL, 6.83 mmol) were added to the resulting reaction mixture, and BF was added to the resulting reaction mixture. ３ ・OET ２ (0.865 mL, 6.83 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. The reaction mixture was sequentially washed with saturated ammonium chloride aqueous solution and saturated saline solution, and the organic layer was dried over magnesium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in methanol, washed twice with n-hexane, and the methanol layer was concentrated under reduced pressure to obtain 13.8 g of compound aa4-013 as a white solid (93% yield, 2 steps). LCMS (ESI) m / z = 542.1 [M+H] ＋ Retention time: 1.00 minutes (Analysis conditions: SQDFA-01)

[0256] Synthesis of compound aa4-014 (Fmoc-MeAbu(3-Pyr-2-OMe)-OH)

[0257] Compound aa4-014-a (10.3 g, 23.8 mmol, CAS number: 2349667-40-7), toluene (119 mL), magnesium sulfate (7.17 g, 59.5 mmol), paraformaldehyde (2.15 g, 71.4 mmol), and TFA (7.29 mL, 95.0 mmol) were sequentially added to a reaction vessel, and the mixture was stirred overnight at 40 °C under a nitrogen atmosphere. After filtering off the solid, the filtrate was concentrated under reduced pressure. DCM (10 v / w) was added to the obtained residue, and the mixture was sequentially washed with water (20 v / w), 0.5 M disodium hydrogen phosphate aqueous solution (20 v / w), and saturated brine (10 v / w). The organic layer was then dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain compound aa4-014-b as the crude product. To the reaction vessel of the crude product of the obtained compound aa4-014-b, DCM (238 mL), TES (11.4 mL, 71.5 mmol), and water (0.429 mL, 23.8 mmol) were added. BF was added to the resulting reaction mixture. ３ ・OET ２ (12.1 mL, 95.0 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. TES (2.85 mL, 17.9 mmol) and water (0.107 mL, 5.95 mmol) were added to the reaction mixture, and BF was added. ３ ・OET ２ (3.02 mL, 23.8 mmol) was added dropwise, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (20 v / w) and then sequentially with saturated saline solution (10 v / w), after which the organic layer was concentrated under reduced pressure. The resulting residue was mixed with 5% sodium carbonate aqueous solution (20 v / w) and washed with TBME / n-hexane (1 / 1, 20 v / w). Phosphoric acid was added to the aqueous layer to adjust the pH to 3-4, then extracted with TBME (20 v / w), and the resulting organic layer was washed with saturated saline solution (10 v / w) and dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. Acetonitrile and water were added to the resulting residue, and after freeze-drying, 9.98 g of compound aa4-014 was obtained as a white solid (yield 94%, 2 steps). LCMS (ESI) m / z = 447.3 [M+H] ＋Retention time: 0.86 minutes (Analysis conditions: SQDFA-01)

[0258] Synthesis of compound aa4-015 (Fmoc-MeAbu(3-Pyr-5-OMe)-OH)

[0259] Compound aa4-015-a (1.00 g, 2.31 mmol, CAS number: 2349456-42-2) was used as the starting material, and the crude product of compound aa4-015-b was obtained by the same method as the synthesis of compound aa4-014-b. DCM (23.1 mL), TES (1.11 mL, 6.94 mmol), and water (0.042 mL, 2.31 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-015-b. BF was added to the resulting reaction mixture. ３ ・OET ２ (1.17 mL, 9.25 mmol) was added dropwise, and the mixture was stirred overnight at room temperature. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution (20 v / w) and then sequentially with saturated saline solution (10 v / w). The organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography (0.1% FA aqueous solution / 0.1% FA acetonitrile solution). Further purification by reverse-phase silica gel column chromatography (water / acetonitrile) yielded 0.795 g of compound aa4-015 as a white solid (77% yield, 2 steps). LCMS (ESI) m / z = 447.3 [M+H] ＋ Retention time: 0.63 minutes (Analysis conditions: SQDFA-01)

[0260] Synthesis of compound aa4-016 (Fmoc-MeAbu(2-Pyr)-OH)

[0261] Compound aa4-016-a (10.0 g, 24.9 mmol, CAS number: 1260601-08-8), toluene (124 mL), magnesium sulfate (7.48 g, 62.1 mmol), paraformaldehyde (2.24 g, 74.5 mmol), and TFA (7.61 mL, 99.0 mmol) were sequentially added to a reaction vessel, and the mixture was stirred overnight at 40 °C under a nitrogen atmosphere. Ethyl acetate (10 v / w) was added to the reaction mixture, and the solid was filtered off. The filtrate was concentrated under reduced pressure. Ethyl acetate (10 v / w) and acetonitrile (1 v / w) were added to the resulting residue, and the mixture was washed with 1 M dipotassium hydrogen phosphate aqueous solution (10 v / w). The organic layer was washed with 3.5% potassium bicarbonate aqueous solution (5 v / w), and then the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain compound aa4-016-b as the crude product. In the reaction vessel containing the crude product of compound aa4-016-b, 124 mL of DCE, 35.6 mL of TES (224 mmol), and 51.3 mL of TFA (671 mmol) were added, and the mixture was stirred overnight at 60 °C. After concentrating the reaction mixture under reduced pressure, ethyl acetate (15 v / w) was added to the resulting residue, and it was washed with 1 M dipotassium hydrogen phosphate aqueous solution (20 v / w). Acetonitrile (7 v / w) was added to the organic layer, and it was washed with 1 M dipotassium hydrogen phosphate aqueous solution (10 v / w). Then, acetonitrile (1 v / w) was added to the organic layer, and it was washed with 1 M dipotassium hydrogen phosphate aqueous solution (10 v / w). After adding n-hexane (5 v / w) to the organic layer, back-extraction was performed with a 3.5% potassium bicarbonate aqueous solution (10 v / w), and the aqueous layer was washed with toluene / n-hexane (1 / 9, 10 v / w). The pH was adjusted to 6 by adding a 1 M potassium dihydrogen phosphate aqueous solution to the aqueous layer, and then extracted twice with ethyl acetate (10 v / w). The resulting organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The obtained residue was then concentrated under reduced pressure three times with the addition of DCM / TBME (1 / 1, 20 v / w). Acetonitrile and water were added to the resulting residue, and after freeze-drying, 8.64 g of compound aa4-016 was obtained as a grayish-white solid (yield 83%, 2 steps). LCMS (ESI) m / z = 417.3 [M+H] ＋Retention time: 0.53 minutes (Analysis conditions: SQDFA-01)

[0262] Synthesis of compound aa4-017 (Fmoc-MeAbu(3-Pyr-4-Me)-OH)

[0263] Using compound aa4-017-a (10.0 g, 24.0 mmol, CAS number: 2349455-13-4) as a starting material, the crude product of compound aa4-017-b was obtained by the same method as the synthesis of compound aa4-016-b. Using the obtained crude product of compound aa4-017-b as a starting material, 8.81 g of compound aa4-017 was obtained as a grayish-white solid (yield 85%, 2 steps) by the same method as the synthesis of compound aa4-016. LCMS (ESI) m / z = 431.3 [M+H] ＋ Retention time: 0.51 minutes (Analysis conditions: SQDFA-01)

[0264] Synthesis of compound aa4-018 (Fmoc-MeAbu(4-Pyr-35-F2)-OH)

[0265] Compound aa4-018-a (5.00 g, 11.4 mmol, CAS number: 2350658-87-4), toluene (114 mL), magnesium sulfate (3.43 g, 28.5 mmol), paraformaldehyde (1.03 g, 34.2 mmol), and TFA (3.48 mL, 45.6 mmol) were sequentially added to a reaction vessel, and the mixture was stirred overnight at 40 °C under a nitrogen atmosphere. Ethyl acetate (10 v / w) was added to the reaction mixture, and the solid was filtered off. The filtrate was concentrated under reduced pressure to obtain compound aa4-018-b as the crude product. Using the obtained crude product of compound aa4-018-b as the starting material, compound aa4-018 was obtained in 5.22 g (yield 101%, 2 steps) as white amorphous crystals by the same method as the synthesis of compound aa4-016. LCMS (ESI) m / z = 453.4 [M+H] ＋ Retention time: 0.82 minutes (Analysis conditions: SQDFA-01)

[0266] Synthesis of compound aa4-019 (Fmoc-MeAbu(4-Pyr-3-CF3)-OH)

[0267] Compound aa4-019-a (5.00 g, 10.6 mmol, CAS number: 2349925-90-0) was used as the starting material, and compound aa4-019-b was obtained as a crude product by the same method as the synthesis of compound aa4-018-b. DCE (53.2 mL), TES (15.3 mL, 95.7 mmol), and TFA (21.9 mL, 287 mmol) were added to the reaction vessel of the obtained crude product of compound aa4-019-b, and the mixture was stirred overnight at 60 °C. After concentrating the reaction mixture under reduced pressure, ethyl acetate (10 v / w) was added to the resulting residue, and the mixture was sequentially washed with 1 M dipotassium hydrogen phosphate aqueous solution (30 v / w) and 1 M dipotassium hydrogen phosphate aqueous solution (10 v / w). After adding n-hexane (5 v / w) to the organic layer, back-extraction was performed with a 3.5% potassium bicarbonate aqueous solution (10 v / w), and the aqueous layer was washed with toluene / n-hexane (1 / 9, 10 v / w). The pH was adjusted to 6 by adding a 1 M potassium dihydrogen phosphate aqueous solution to the aqueous layer, and then extracted twice with ethyl acetate (10 v / w). The resulting organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The obtained residue was then concentrated under reduced pressure with TBME (10 v / w) three times. Acetonitrile and water were added to the residue, and after freeze-drying, 5.08 g of compound aa4-019 was obtained as white amorphous crystals (99% yield, 2 steps). LCMS (ESI) m / z = 485.4 [M + H] ＋ Retention time: 0.84 minutes (Analysis conditions: SQDFA-01)

[0268] Synthesis of compound aa4-020 (Fmoc-MeAbu(4-Pyr-3-Cl)-OH)

[0269] Compound aa4-020-a (15.0 g, 34.2 mmol, CAS number: 2350111-24-7) was used as the starting material, and compound aa4-020-b was obtained as the crude product by the same method as the synthesis of compound aa4-018-b. Using the obtained crude product of compound aa4-020-b as the starting material, compound aa4-020 was obtained in 11.4 g (74% yield, 2 steps) as a white amorphous crystal by the same method as the synthesis of compound aa4-016. LCMS (ESI) m / z = 451.5 [M + H] ＋ Retention time: 0.81 minutes (Analysis conditions: SQDFA-01)

[0270] Synthesis of compound aa4-021 (Fmoc-MeAbu(4-Pyr-3-Me)-OH)

[0271] Compound aa4-021-a (9.30 g, 22.3 mmol, CAS number: 2349891-63-8) was used as a starting material, and compound aa4-021-b was obtained as a crude product by the same method as the synthesis of compound aa4-018-b. Using the obtained crude product of compound aa4-021-b as a starting material, compound aa4-021 was obtained in 9.03 g (yield 94%, 2 steps) as a grayish-white solid by the same method as the synthesis of compound aa4-016. LCMS (ESI) m / z = 431.3 [M+H] ＋ Retention time: 0.51 minutes (Analysis conditions: SQDFA-01)

[0272] Synthesis of compound aa4-022 (Fmoc-MeAbu(4-Pyr-3-F)-OH)

[0273] Compound aa4-022-a (5.00 g, 11.9 mmol, CAS number: 2349346-76-3), toluene (59.5 mL), magnesium sulfate (3.58 g, 29.7 mmol), paraformaldehyde (1.07 g, 35.7 mmol), and TFA (3.64 mL, 47.6 mmol) were sequentially added to a reaction vessel, and the mixture was stirred overnight at 40 °C under a nitrogen atmosphere. After filtering off the solid, the solid was washed with DCM, and the combined filtrate was concentrated under reduced pressure. DCM (10 v / w) was added to the resulting residue, and it was sequentially washed with water (20 v / w), 1 M dipotassium hydrogen phosphate aqueous solution (10 v / w), and saturated brine (10 v / w). The extraction procedure by adding DCM (5 v / w) to the aqueous layer was repeated three times, and the combined organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain 3.73 g (73% yield) of compound aa4-022-b as a yellow solid. LC-MS (ESI) m / z = 433.6 [M + H] ＋ Retention time: 0.81 minutes (Analysis conditions: SQDFA-01)

[0274] Starting with compound aa4-022-b (2.10 g, 4.86 mmol), compound aa4-022 was obtained as a white solid in 1.38 g (65% yield) using the same method as for the synthesis of compound aa4-016. LCMS (ESI) m / z = 435.3 [M+H] ＋ Retention time: 0.73 minutes (Analysis conditions: SQDFA-01)

[0275] Synthesis of compound aa4-023 (Fmoc-EtGly(cBu)-OH)

[0276] Compound aa1-025 (5.00 g, 14.2 mmol), DCE (17.8 mL), magnesium sulfate (5.14 g, 42.7 mmol), paraaldehyde (5.64 g, 42.7 mmol), and TFA (9.87 mL, 128 mmol) were sequentially added to a reaction vessel, and the mixture was stirred overnight at 60 °C under a nitrogen atmosphere. After filtering off the solid, the filtrate was concentrated under reduced pressure. DCE, ethyl acetate, and n-hexane were added to the resulting residue, and it was washed with saturated sodium bicarbonate aqueous solution. The organic layer was concentrated under reduced pressure to obtain compound aa4-023-b as the crude product. DCE (40.0 mL), TES (20.5 mL, 128 mmol), and TFA (29.6 mL, 384 mmol) were added to the reaction vessel of the crude product of compound aa4-023-b, and the mixture was stirred overnight at 60 °C. After concentrating the reaction mixture under reduced pressure, ethyl acetate (20 v / w) was added to the resulting residue. The mixture was then sequentially washed with saturated sodium bicarbonate aqueous solution, phosphoric acid aqueous solution, and saturated brine. The resulting organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography to obtain 4.76 g of compound aa4-023 (88% yield, 2 steps). LC-MS (ESI) m / z = 380.2 [M+H] ＋ Retention time: 0.90 minutes (Analysis conditions: SQDFA-01)

[0277] Synthesis of compound aa4-024 (Fmoc-EtGly(cPr)-OH)

[0278] Compound aa1-027 (600 g, 1.78 mol), toluene (2.40 L), magnesium sulfate (642 g, 5.34 mol), and paraaldehyde (353 g, 2.67 mol) were added to a reaction vessel. TFA (274 mL, 3.56 mol) was added dropwise at room temperature, and the mixture was stirred at 60 °C for 2 hours under a nitrogen atmosphere. Water (10 v / w) was added to the reaction mixture, and the resulting organic layer was sequentially washed with water (5 v / w), 1 M dipotassium hydrogen phosphate aqueous solution (5 v / w), 3.5% potassium bicarbonate aqueous solution (5 v / w), and saturated brine (5 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain compound aa4-024-b as the crude product. To the reaction vessel containing the crude product of the obtained compound aa4-024-b, toluene (2.96 L) and TES (651 mL, 4.07 mol) were added. Titanium tetrachloride (446 mL, 4.07 mol) was then added dropwise under ice cooling, and the mixture was stirred at room temperature for 1 hour under a nitrogen atmosphere. Water (5 v / w) was added to the reaction mixture under ice cooling, and the resulting organic layer was back-extracted twice by adding 3.5% potassium bicarbonate aqueous solution / acetonitrile (2 / 1, 10 v / v). The combined aqueous layer was washed with n-hexane (10 v / w), and the pH was adjusted to 2-3 by adding 6 M hydrochloric acid under ice cooling. The mixture was then extracted twice with TBME (10 v / w). The resulting organic layer was concentrated under reduced pressure to obtain 495 g of compound aa4-024 as a white solid (yield 76%, 2 steps). LCMS (ESI) m / z = 366.4 [M+H] ＋ Retention time: 0.83 minutes (Analysis conditions: SQDFA-01)

[0279] Synthesis of compound aa4-025 (Fmoc-EtSer(iPen)-OH)

[0280] Compound aa4-025-a (49.0 g, 123 mmol, CAS No.: 2255321-11-8), toluene (500 mL), magnesium sulfate (29.7 g, 247 mmol), and paraaldehyde (24.4 g, 185 mmol) were added to a reaction vessel. TFA (28.5 mL, 370 mmol) was added dropwise to the reaction mixture at room temperature, and the mixture was stirred at 70 °C for 16 hours under a nitrogen atmosphere. Water was added to the reaction mixture, and it was extracted three times with ethyl acetate. The combined organic layers were washed with saturated brine and then dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain 43 g of compound aa4-025-b as a crude product (82% yield). LCMS (ESI) m / z = 424.3 [M + H] ＋ Retention time: 1.20 minutes (Analysis conditions: PMFA-01)

[0281] To a reaction vessel containing the crude product of compound aa4-025-b (50.0 g, 118 mmol), toluene (500 mL) and TES (56.6 mL, 354 mmol) were added. Titanium tetrachloride (25.9 mL, 236 mmol) was then added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 15 minutes. Water was added to the reaction mixture, and it was extracted three times with ethyl acetate. The combined organic layers were dried over sodium sulfate, the drying agent was filtered off, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography (water / acetonitrile) to obtain 32 g of compound aa4-025 as a yellow oily substance (yield 64%). LCMS (ESI) m / z = 426.3 [M + H] ＋ Retention time: 1.08 minutes (Analysis conditions: SQDFA-01)

[0282] Synthesis of compound aa4-026 (Fmoc-nPrGly(cPr)-OH)

[0283] Compound aa1-027 (2.10 kg, 6.225 mol), toluene (8.40 L), magnesium sulfate (4.50 kg, 37.4 mol), and propionaldehyde (4.02 L, 56.0 mol) were added to the reaction vessel. TFA (4.29 L, 56.0 mol) was added dropwise to the reaction mixture at room temperature, and the mixture was stirred at 60 °C for 2 hours under a nitrogen atmosphere. Water (10 v / w) was added to the reaction mixture at room temperature, and the resulting organic layer was sequentially washed with 1 M dipotassium hydrogen phosphate aqueous solution (5 v / w), 3.5% potassium bicarbonate aqueous solution (5 v / w), and saturated brine (5 v / w), after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain compound aa4-026-b as the crude product. To the reaction vessel containing the crude product of the obtained compound aa4-026-b, toluene (10.1 L) and TES (3.21 L, 20.1 mol) were added. Titanium tetrachloride (1.47 L, 13.4 mol) was then added dropwise under ice cooling, and the mixture was stirred at room temperature for 1 hour under a nitrogen atmosphere. Water (5 v / w) was added to the reaction mixture under ice cooling, and the resulting organic layer was back-extracted twice by adding 3.5% potassium bicarbonate aqueous solution / acetonitrile (2 / 1, 10 v / v). The combined aqueous layer was washed with n-hexane (10 v / w), and the pH was adjusted to 2-3 by adding 6 M hydrochloric acid under ice cooling. The mixture was then extracted twice with TBME (10 v / w). The resulting organic layer was concentrated under reduced pressure to obtain 1.55 kg of compound aa4-026 as a grayish-white solid (yield 66%, 2 steps). LCMS (ESI) m / z = 380.3 [M+H] ＋ Retention time: 0.88 minutes (Analysis conditions: SQDFA-01)

[0284] Synthesis of compound aa4-027 (Fmoc-D-nPrAla-OH)

[0285] Compound aa4-027-a (20.0 g, 106 mmol, CAS No.: 7764-95-6), THF (350 mL), and allyl bromide (27.2 mL, 317 mmol) were added to a reaction vessel. Sodium hydride (14.8 g, 60 Wt%, 370 mmol) was gradually added to the reaction mixture over 15 minutes under ice cooling, and the mixture was stirred under ice cooling for 1 hour. THF (350 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 3 days. After adding ice-cold water to the reaction mixture under ice cooling, the aqueous layer was washed with ethyl acetate. Concentrated hydrochloric acid was added to the aqueous layer to adjust the pH to 3, and then the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The obtained residue was purified by reverse-phase silica gel column chromatography (0.1% FA aqueous solution / 0.1% FA acetonitrile solution) to obtain 20 g of compound aa4-027-b as a colorless oily substance (yield 82%). LCMS (ESI) m / z = 230.3 [M+H] ＋ Retention time: 0.72 minutes (Analysis conditions: PMFA-01)

[0286] To the reaction vessel, 11.0 g, 48.0 mmol of compound aa4-027-b was added, followed by the addition of methanol (160 mL) and palladium-carbon (3.58 g, 33.6 mmol) under a nitrogen atmosphere. The reaction vessel was degassed under reduced pressure, repressurized with hydrogen, and stirred at room temperature for 2 hours. After filtering off the solid, the filtrate was concentrated under reduced pressure to obtain compound aa4-027-c as the crude product. To the reaction vessel of the crude product of compound aa4-027-c, 170 mL of TFE was added, followed by the dropwise addition of TMSCl (7.90 mL, 62.3 mmol) under a nitrogen atmosphere at room temperature, and the mixture was stirred under a nitrogen atmosphere at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain compound aa4-027-d as the crude product. To the reaction vessel of the crude product of compound aa4-027-d obtained, water (179 mL), DIPEA (55.8 mL, 320 mmol), 1,4-dioxane (240 mL), and Fmoc-OSu (28.8 g, 85.4 mmol) were added, and the mixture was stirred at room temperature for 30 minutes. After adding 20% ​​FA aqueous solution, the mixture was extracted three times with ethyl acetate (200 mL). The combined organic layer was washed with saturated brine and dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography (0.1% FA aqueous solution / 0.1% FA acetonitrile solution) to obtain 12.9 g of compound aa4-027 as a grayish-white solid (yield 75%, 3 steps). LCMS (ESI) m / z = 354.3 [M+H] ＋ Retention time: 0.85 minutes (Analysis conditions: SQDFA-01)

[0287] Synthesis of compound aa4-028 (Fmoc-MeSer(cBu-3-F2)-OH)

[0288] Compound aa4-028-a (CAS number: 2255322-63-3) was synthesized according to the method described in WO2021 / 090855.

[0289] Compound aa4-028-a (8.49 g, 26.3 mmol), toluene (52.5 mL), and 3,3-difluorocyclobutanol (3.80 mL, 44.6 mmol) were added to the reaction vessel. The resulting reaction mixture was cooled on ice and then subjected to BF ３・OET ２ (0.495 mL, 3.94 mmol) was added dropwise, and the mixture was stirred under a nitrogen atmosphere and ice cooling for 1 hour. A saturated sodium bicarbonate aqueous solution / water (1 / 1) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate / n-hexane) to obtain 4.30 g of compound aa4-028-b as a colorless oily substance (38% yield). LCMS (ESI) m / z = 432.3 [M+H] ＋ Retention time: 0.93 minutes (Analysis conditions: SQDFA-01)

[0290] In a reaction vessel, calcium chloride (16.6 g, 150 mmol) was dissolved in water (41.5 mL), lithium hydroxide monohydrate (1.67 g, 39.9 mmol) was added, and the mixture was stirred at room temperature for 5 minutes. Then, IPA (166 mL) and a solution of compound aa4-028-b (4.30 g, 9.97 mmol) dissolved in THF (41.5 mL) were added, and the mixture was stirred at room temperature for 4 hours. After adding 1 M hydrochloric acid solution (59.8 mL) to the reaction mixture, volatile components were removed by distillation under reduced pressure. Water was added to the resulting aqueous layer, and it was extracted with ethyl acetate. The organic layer was sequentially washed with water and saturated brine, and dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting solid was washed with ethyl acetate / n-hexane (1 / 5, 20 v / w), dried under reduced pressure, and 3.50 g (84% yield) of compound aa4-028-c was obtained as a white solid. LCMS (ESI) m / z = 418.3 [M+H] ＋ Retention time: 0.84 minutes (Analysis conditions: SQDFA-01)

[0291] Compound aa4-028-c (1.98 g, 4.74 mmol), toluene (5.93 mL), paraformaldehyde (0.427 g, 14.2 mmol), and TFA (3.27 mL, 42.7 mmol) were sequentially added to a reaction vessel, and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. The reaction mixture was concentrated under reduced pressure, and ethyl acetate was added. The resulting solution was washed twice with saturated sodium bicarbonate aqueous solution and sequentially with saturated brine, and the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure to obtain compound aa4-028-d as the crude product. DCM (19.2 mL), TES (1.89 mL, 11.9 mmol), and water (0.107 mL, 5.93 mmol) were added to the reaction vessel of the crude product of compound aa4-028-d. The resulting reaction mixture was refrigerated under ice cooling with BF ３ ・OET ２ (1.50 mL, 11.9 mmol) was added dropwise, and the mixture was stirred at room temperature for 3 hours. A saturated ammonium chloride aqueous solution / water (1 / 1) was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and then dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile, washed twice with n-hexane, and the acetonitrile layer was concentrated under reduced pressure to obtain 1.95 g of compound aa4-028 as a white amorphous crystal (95% yield, 2 steps). LCMS (ESI) m / z = 432.1 [M+H] ＋ Retention time: 0.85 minutes (Analysis conditions: SQDFA-01)

[0292] Synthesis of compound aa4-029 (Fmoc-MeSer(cHex-4-F2)-OH)

[0293] Compound aa4-028-a (30.0 g, 92.8 mmol), toluene (180 mL), and 4,4-difluorocyclohexanol (18.7 mL, 158 mmol) were added to the reaction vessel. The resulting reaction mixture was cooled on ice using BF. ３ ・OET ２(1.75 mL, 13.9 mmol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2.5 hours. After adding water to the reaction mixture, it was extracted twice with ethyl acetate, and the resulting organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure, and the resulting residue was washed with TBME / n-hexane (3 / 7), dried under reduced pressure, and 20 g of compound aa4-029-b was obtained as a white solid (47% yield). LCMS (ESI) m / z = 460.2 [M+H] ＋ Retention time: 0.81 minutes (Analysis conditions: PMTFA-01)

[0294] Starting with compound aa4-029-b (20.0 g, 43.5 mmol), compound aa4-029-c was synthesized as a white solid, yielding 13 g (67% yield), using the same method as for the synthesis of compound aa4-028-c. LC-MS (ESI) m / z = 446.2 [M+H] ＋ Retention time: 0.84 minutes (Analysis conditions: SQDFA-01)

[0295] Compound aa4-029-c (3.00 g, 6.73 mmol), DCM (44.9 mL), magnesium sulfate (2.03 g, 16.8 mmol), and paraformaldehyde (0.607 g, 20.2 mmol) were added to the reaction vessel. BF was added to the resulting reaction mixture. ３ ・OET ２ (1.02 mL, 8.08 mmol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 3 hours. After filtering off the solid, the solid was washed with DCM (40 mL), and the washing solution was combined with the solid to obtain a DCM solution of compound aa4-029-d. To the obtained DCM solution of compound aa4-029-d, TES (2.69 mL, 16.8 mmol) and water (0.121 mL, 6.73 mmol) were added. The resulting reaction mixture was cooled on ice and then subjected to BF ３ ・OET ２(1.28 mL, 10.1 mmol) was added dropwise, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was washed twice with saturated ammonium chloride aqueous solution and then sequentially with saturated saline solution, after which the organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in acetonitrile (50 mL), washed three times with n-hexane (30 mL), and then the acetonitrile layer was concentrated under reduced pressure. The obtained residue was purified by reverse-phase silica gel column chromatography to obtain 2.55 g of compound aa4-029 as a white solid (yield 82%, 2 steps). LCMS (ESI) m / z = 460.2 [M+H] ＋ Retention time: 0.88 minutes (Analysis conditions: SQDFA-01)

[0296] Synthesis of compound aa4-030 (Fmoc-MeSer(Me-cHex)-OH)

[0297] Compound aa4-028-a (1.01 kg, 3.12 mol), toluene (6.06 L), and cyclohexanemethanol (654 mL, 5.31 mol) were added to the reaction vessel. The resulting reaction mixture was cooled on ice and then fermented with BF ３ ・OET ２ (58.8 mL, 0.469 mol) was added dropwise, and the mixture was stirred under a nitrogen atmosphere at room temperature for 2 hours. Water (6 v / w) was added to the reaction mixture, and the resulting organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. TBME (7 v / w) and ethyl acetate (1 v / w) were added to the resulting residue, and the mixture was stirred at room temperature for 1 hour. The resulting solid was filtered, washed twice with n-heptane (2 v / w), and dried under reduced pressure to obtain 929 g (68% yield) of compound aa4-030-b as a white solid. LCMS (ESI) m / z = 438.2 [M + H] ＋ Retention time: 9.00 minutes (Analysis conditions: PMFA-02)

[0298] Starting with compound aa4-030-b (929 g, 2.12 mmol), compound aa4-030-c was synthesized using the same method as for compound aa4-028-c, yielding 681 g of aa4-030-c as a white solid (76% yield). LC-MS (ESI) m / z = 424.1 [M+H] ＋ Retention time: 1.98 minutes (Analysis conditions: PMFA-03)

[0299] Compound aa4-030-c (681 g, 1.61 mmol), DCM (11.6 L), magnesium sulfate (484 g, 4.02 mol), and paraformaldehyde (145 g, 4.83 mol) were added to the reaction vessel. BF was added to the resulting reaction mixture. ３ ・OET ２ (242 mL, 1.93 mol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. After filtering off the solid, the solid was washed with DCM (5.00 L), and the washing solution was combined with the solid to obtain a DCM solution of compound aa4-030-d. To the obtained DCM solution of compound aa4-030-d, TES (640 mL, 4.02 mol) and water (29.0 mL, 1.61 mol) were added. BF was refrigerated under ice cooling. ３ ・OET ２ (303 mL, 2.41 mol) was added dropwise, and the mixture was stirred at room temperature for 5 hours. Saturated ammonium chloride aqueous solution (10 v / w) was added to the reaction mixture, and the resulting organic layer was sequentially washed with saturated ammonium chloride aqueous solution (5 v / w) and saturated brine (5 v / w), and then concentrated under reduced pressure. TBME (10 v / w) and n-heptane (10 v / w) were added to the resulting residue, and the mixture was stirred at room temperature for 15 minutes. Then, 3.5% potassium bicarbonate aqueous solution (10 v / w) and acetonitrile (5 v / w) were added, and the mixture was stirred at room temperature for 15 minutes. The resulting aqueous layer was washed twice with TBME / n-hexane (1 / 1, 10 v / w). Under ice cooling, 6 M hydrochloric acid solution was added to the aqueous layer to adjust the pH to 2-3, and then the mixture was extracted twice with DCM (5 v / w). The organic layer was washed with saturated brine (10 v / w) and then dried over sodium sulfate. After filtering off the desiccant, the filtrate was concentrated under reduced pressure to obtain 529 g of compound aa4-030 as a white solid (75% yield, 2 steps). LC-MS (ESI) m / z = 438.3 [M+H]＋ Retention time: 3.29 minutes (Analysis conditions: SQDFA-03)

[0300] Synthesis of compound aa4-031 (Fmoc-MeSer(neoPent)-OH)

[0301] Compound aa4-028-a (50.0 g, 155 mmol), DCM (500 mL), and neopentyl alcohol (28.5 mL, 263 mmol) were added to the reaction vessel. The resulting reaction mixture was cooled on ice and then subjected to BF ３ ・OET ２ (2.91 mL, 23.2 mmol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2.5 hours. After adding water to the reaction mixture, it was extracted twice with ethyl acetate. The combined organic layers were washed with saturated brine and dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure, and the resulting residue was washed with TBME / n-hexane (3 / 7) and dried under reduced pressure to obtain 26 g of compound aa4-031-b as a white solid (41% yield). LCMS (ESI) m / z = 412.2 [M + H] ＋ Retention time: 1.39 minutes (Analysis conditions: PMTFA-02)

[0302] Starting with compound aa4-031-b (17.0 g, 41.3 mmol), compound aa4-031-c was obtained as a white solid in 14 g (85% yield) using the same method as the synthesis of compound aa4-028-c. LCMS (ESI) m / z = 398.1 [M+H] ＋ Retention time: 1.28 minutes (Analysis conditions: PMTFA-02)

[0303] Starting with compound aa4-031-c (50.0 g, 126 mmol), compound aa4-031 was obtained as a white solid in 46.5 g (90% yield, 2 steps) using the same method as for the synthesis of compounds aa4-029-d and aa4-029. LCMS (ESI) m / z = 412.3 [M+H] ＋ Retention time: 1.02 minutes (Analysis conditions: SQDFA-01)

[0304] Synthesis of compound aa4-032 (Fmoc-Ser(Me-3R-THF)-OH)

[0305] Compound aa4-028-a (10.0 g, 30.9 mmol), toluene (100 mL), and 3S-oxolan-3-ylmethanol (3.48 g, 34.0 mmol) were added to the reaction vessel. The resulting reaction mixture was then subjected to BF under ice cooling. ３ ・OET ２ (0.584 mL, 4.64 mmol) was added dropwise, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2.5 hours. After adding saturated ammonium chloride aqueous solution to the reaction mixture, it was extracted twice with ethyl acetate, and the combined organic layer was dried over sodium sulfate. After filtering off the drying agent, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate / petroleum ether) to obtain 4.3 g of compound aa-032-b as a colorless oily substance (yield 32%). LCMS (ESI) m / z = 448.2 [M + Na] ＋ Retention time: 0.99 minutes (Analysis conditions: PMTFA-03)

[0306] Starting with compound aa4-032-b (4.30 g, 10.1 mmol), compound aa4-032 was obtained as a white solid in 2.90 g (70% yield) using the same method as for the synthesis of compound aa4-028-c. LCMS (ESI) m / z = 412.4 [M+H] ＋ Retention time: 0.72 minutes (Analysis conditions: SQDFA-01)

[0307] Synthesis of compound aa4-033 (Fmoc-Ser(Me-3S-THF)-OH)

[0308] Starting with compound aa4-028-a (5.20 g, 16.1 mmol) and 3R-oxolan-3-ylmethanol (1.81 g, 17.7 mmol), compound aa4-033-b was obtained as a colorless oily substance in an amount of 2.1 g (30% yield) using the same method as for the synthesis of compound aa4-032-b. LCMS (ESI) m / z = 426.1 [M+H] ＋ Retention time: 0.85 minutes (Analysis conditions: PMFA-04)

[0309] Starting with compound aa4-032-b (2.10 g, 4.94 mmol), compound aa4-033 was obtained as a grayish-white solid in an amount of 1.8 g (88% yield) using the same method as the synthesis of compound aa4-028-c. LCMS (ESI) m / z = 412.3 [M+H] ＋ Retention time: 0.73 minutes (Analysis conditions: SQDFA-01)

[0310] Synthesis of compound aa4-034 (Fmoc-MeAbu(3-Pyr-2-Me)-OH)

[0311] Compound aa4-034-a (CAS number: 2490159-54-9) was synthesized according to the method described in WO2020 / 189540.

[0312] Compound aa4-034-a (2.00 g, 3.42 mmol), DMA (7.60 mL), zinc powder (1.12 g, 17.1 mmol), and 3-bromo-2-methylpyridine (0.774 mL, 6.84 mmol) were added to the reaction vessel. To the resulting reaction mixture, nickel(II) bromide 4,4'-di-tert-butyl-2,2'-bipyridyl complex (NiBr ２A solution of (dtbbpy) (0.500 g, 1.03 mmol) dissolved in DMA (3.80 mL) was added dropwise under ice cooling, and the mixture was stirred for 15 minutes under a nitrogen atmosphere and under ice cooling. TMSCl (0.216 mL, 1.71 mmol) was added to the resulting reaction mixture, and the mixture was stirred for 2 hours under a nitrogen atmosphere and under ice cooling. The solid was removed by Celite filtration, and the Celite was washed with ethyl acetate (15 v / w). The combined organic layers were then washed sequentially with 15% ammonium chloride aqueous solution (30 v / w), 8% EDTA-2Na aqueous solution (30 v / w), 5% sodium carbonate ...

Claims

Compounds represented by the following formula (1) or their salts: During the ceremony, R １ is one of the following (a1) to (a4): (a1) R １ C １ ~C ６ Alkyl, or C ２ ~C ７ It is Alkenil; (a2) R １ and P １ together with the carbon atom to which R １ is bonded and the nitrogen atom to which P １ is bonded form a 4- to 7-membered monocyclic saturated heterocyclic ring, wherein said 4- to 7-membered monocyclic saturated heterocyclic ring may be substituted with one or more groups independently selected from the group consisting of halogen, C １ -C ６ alkyl, C ２ -C ７ alkenyl, C １ -C ６ alkoxy, halo C １ -C ６ alkoxy, C １ -C ６ alkoxy C １ -C ６ alkyl and C ６ -C １４ aryl, and said 4- to 7-membered monocyclic saturated heterocyclic ring may be fused to a 3- to 8-membered saturated alicyclic ring; (a3) R １ R ６ Together with C ４ ~C ８ Alkylene, or C ４ ~C ８ Forms alkenylenes; (a4) R １ and P １ R １ The carbon atom to which it is bonded, and P １ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle is further X １ It is replaced with X １ is R ６ Together with C ４ ~C ８ Alkylene, or C ４ ~C ８ Forms alkenylenes; P １ R １ and P １ Unless it forms a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms or C １ ~C ６ It is alkyl, Q １ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ２ The formula is as follows: (In the formula, * is R in equation (1) ２ It represents the carbon atom to which it is bonded. X ２１ This is either (b1) or (b2) below, (b1) X ２１ C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, or Halo C １ ~C ６ It is alkyl; (b2)X ２１ is, X ２１ and X ２２ Together with the bonded carbon atoms, they form a 3- to 8-membered saturated alicyclic ring: X ２２ is, X ２１ and X ２２ Unless it forms a 3- to 8-membered saturated alicyclic ring, a hydrogen atom or C １ ~C ６ It is alkyl, X ２３ is a hydrogen atom, or C １ ~C ６ It is represented as (which is alkyl), P ２ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ２ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ３ represents C １ -C ６ alkoxy C １ -C ６ alkyl, C ３ -C ８ cycloalkyl C １ -C ６ alkyl, C ３ -C ８ cycloalkoxy C １ -C ６ alkyl, C ３ -C ８ cycloalkyl C １ -C ６ alkoxy C １ -C ６ alkyl, C ３ -C ８ cycloalkylidene C １ -C ６ alkyl, C ６ -C １４ aryloxy C １ -C ６ alkyl, or C ７ -C １４ aralkyl, each of which may be substituted with one or more groups independently selected from the group consisting of halogen, C １ -C ６ alkyl, and C １ -C ６ alkoxy; P ３ C is a hydrogen atom. １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, Q ３ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ４ is one of the following (d1) to (d3): (d1) R ４ C is a hydrogen atom. １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ It is alkyl; (d2) R ４ and P ４ R ４ The carbon atom to which it is bonded, and P ４ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups selected more independently from the group consisting of aryl groups; (d3)R ４ and Q ４ R ４ and Q ４ Together with the bonded carbon atoms, it forms a 3- to 8-membered saturated alicyclic ring. P ４ R ４ and P ４ Unless it forms a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms or C １ ~C ６ It is alkyl, Q ４ R ４ and Q ４ Except when forming a 3- to 8-membered saturated alicyclic ring, hydrogen atoms, C １ ~C ６ Alkyl, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ They are alkyl groups, each of which may be substituted with one or more halogens. R ５ is aminocarbonyl C １ ~C ６ Alkoxy C １ ~C ６ Alkyl (the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ C may be substituted with a cycloalkylamino or a 3- to 10-membered monocyclic cyclic amino, or a 4- to 7-membered heterocyclyl. １ ~C ６ Alkoxy C １ ~C ６ It is alkyl, P ５ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ５ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ６ R １ Unless (a3) ​​or (a4), the following formula (In the formula, ** is R in equation (1) ６ It represents the carbon atom to which it is bonded. X ６１ is either (f1) or (f2) below, (f1)X ６１ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, or C ３ ~C ８ It is a cycloalkoxy; (f2)X ６１ is, X ６１ and X ６２ Together with the bonded carbon atoms, these atoms form a 3-8 member saturated alicyclic ring or a 4-7 member saturated heterocyclic ring, and these 3-8 member saturated alicyclic rings or 4-7 member saturated heterocyclic rings contain halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; X ６２ is, X ６１ and X ６２ Unless it forms a 3- to 8-membered saturated alicyclic ring or a 4- to 7-membered saturated heterocyclic ring, a hydrogen atom or C １ ~C ６ It is alkyl; X ６３ is a hydrogen atom, or C １ ~C ６ It is represented as (which is alkyl), P ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ６ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ７ This is either (h1) or (h2) below, (h1)R ７ C １ ~C ６ It is alkyl; (h2)R ７ and P ７ R ７ The carbon atom to which it is bonded, and P ７ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered saturated heterocycle, and this 4- to 7-membered saturated heterocycle is a halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ It may be substituted with one or more groups selected more independently from the group consisting of aryl groups; P ７ R ７ and P ７ Unless it forms a 4- to 7-membered saturated heterocycle, a hydrogen atom or C １ ~C ６ It is alkyl, Q ７ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ８ is either (i1) or (i2) below, (i1) R ８ C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys; (i2)R ８ and P ８ R ８ The carbon atom to which it is bonded, and P ８ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle contains halogens, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The 4- to 7-membered monocyclic saturated heterocycle may be substituted with one or more groups more independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring; P ８ R ８ and P ８ Except when forming a 4- to 7-membered monocyclic saturated heterocycle, hydrogen atoms, C １ ~C ６ Alkyl, or C ３ ~C ８ Cycloalkyl C １ ~C ６ It is alkyl, Q ８ is a hydrogen atom, or C １ ~C ６ It is alkyl, R ９ C １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, 4-7 member heterocyclyl C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkil, C ６ ~C １０ Aryloxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkylidene C １ ~C ６ Alkyl, 4-9 member heterocyclyloxy C １ ~C ６ Alkyl or 5-10 member heteroaryl C １ ~C ６ The C is alkyl, and each of them may be substituted with a halogen. ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl and 5-10 membered heteroaryl C １ ~C ６ Alkyl is C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy and Halo C １ ~C ６ It may be substituted with one or more groups independently selected from the group consisting of alkoxys. P ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q ９ is a hydrogen atom, or C １ ~C ６ It is alkyl, R １０ is a hydrogen atom, or C １ ~C ６ It is alkyl, P １０ C is a hydrogen atom. １ ~C ６ Alkyl, C ２ ~C ６ Alkenil, C ２ ~C ６ Alkinyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, or C ７ ~C １４ It is aralkyl, and each of them may be substituted with one or more halogens. Q １０ is a hydrogen atom, or C １ ~C ６ It is alkyl, R １１ C is a hydrogen atom. １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, aminocarbonyl (where the amino is -NH ２ Mono C １ ~C ６ Alkylamino, MonoC ３ ~C ８ Cycloalkylamino, diC １ ~C ６ Alkylamino, N-C １ ~C ６ Alkyl-N-C ２ ~C ６ Alkenylamino, N-C １ ~C ６ Alkyl-N-C ３ ~C ８ Cycloalkylamino, diC ３ ~C ８ The aminocarbonyl is a cycloalkylamino or a 3-10 membered cyclic amino, and if the aminocarbonyl is a 3-10 membered monocyclic cyclic aminocarbonyl, it may be condensed with a 3-8 membered saturated alicyclic ring, and may form a spiro ring or a crosslinking ring on the ring, and the aminocarbonyl may be a halogen, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ It may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups. P １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, Q １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, L １１ It is either a single bond or -CM １１ M １２ -, - (CH ２ ) ｎ S (CH ２ ) ｍ -, - (CH ２ ) ｎ S(O)(CH ２ ) ｍ - or - (CH ２ ) ｎ S(O) ２ (CH ２ ) ｍ - where n and m are independently 1 or 2, and M １１ is a hydrogen atom, or C １ ~C ６ It is alkyl, M １２ is a hydrogen atom, or C １ ~C ６ It is alkyl. R １ and P １ However, R １ The carbon atom to which it is bonded, and P １ Together with the nitrogen atom to which it is bonded, it forms a 4- to 7-membered monocyclic saturated heterocycle, and this 4- to 7-membered monocyclic saturated heterocycle is a halogen, C １ ~C ６ Alkyl, C ２ ~C ７ Alkenil, C １ ~C ６ Alkoxy, Halo C １ ~C ６ Alkoxy, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl and C ６ ~C １４ The compound or salt thereof according to claim 1, which may be substituted with one or more groups independently selected from the group consisting of aryls, and the 4- to 7-membered monocyclic saturated heterocycle may be fused with a 3- to 8-membered saturated alicyclic ring. X ２３ The compound or salt thereof according to claim 1 or claim 2, wherein the compound is a hydrogen atom. R ３ However, C may be substituted with one or more halogens. ３ ~C ８ Cycloalkoxy C １ ~C ６ Alkyl, or C １ ~C ６ Alkoxy C １ ~C ６ A compound or salt thereof according to any one of claims 1 to 3, wherein the compound is alkyl. R ４ and P ４ However, R ４ The carbon atom to which it is bonded, and P ４ The compound or salt thereof according to any one of claims 1 to 4, wherein the compound and / or a salt thereof are bonded together with a nitrogen atom to form a 4- to 7-membered monocyclic saturated heterocycle. R ５ However, aminocarbonyl C １ ~C ６ Alkoxy C １ ~C ６ A compound or salt thereof according to any one of claims 1 to 5, wherein the compound is alkyl. X ６１ and X ６２ However, X ６１ and X ６２ Together with the bonded carbon atoms, it forms a 4-6 membered saturated alicyclic ring, X ６３ The compound or salt thereof according to any one of claims 1 to 6, wherein the compound is a hydrogen atom. R ７ However, C １ ~C ３ Is it alkyl, or R ７ and P ７ However, R ７ The carbon atom to which it is bonded, and P ７ Together with the bonded nitrogen atom, it forms a 4- or 5-membered saturated heterocycle, and this 4- or 5-membered saturated heterocycle is a halogen and C １ ~C ６ A compound or salt thereof according to any one of claims 1 to 7, which may be substituted with one or more groups independently selected from the group consisting of alkyl groups. R ８ However, C １ ~C ６ Alkyl, hydroxy C １ ~C ６ Alkyl, or C ３ ~C ８ It is a cycloalkyl, and the C ３ ~C ８ Cycloalkyls are halogens, C １ ~C ６ Alkyl and C １ ~C ６ A compound or salt thereof according to any one of claims 1 to 8, which may be substituted with one or more groups independently selected from the group consisting of alkoxys. R ９ However, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ It is alkyl, and the C ３ ~C ８ Cycloalkyl C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy C １ ~C ６ Alkyl, C ７ ~C １４ Aralkyl, or 5-10 member heteroaryl C １ ~C ６ Alkyls are halogens, and C １ ~C ６ A compound or salt thereof according to any one of claims 1 to 9, which may be substituted with one or more groups independently selected from the group consisting of alkyl groups. P １０ However, C may be substituted with one or more halogens. １ ~C ６ Alkyl, or C ２ ~C ６ A compound or salt thereof according to any one of claims 1 to 10, which is an alkenyl. R １１ However, it is a 3-10 member monocyclic cyclic aminocarbonyl, and the 3-10 member monocyclic cyclic aminocarbonyl may be condensed with a 3-8 member saturated alicyclic ring, and may form a spiro ring or a crosslinking ring on the ring, and the atoms forming the ring of the 3-10 member monocyclic cyclic aminocarbonyl are halogens, C １ ~C ６ Alkyl, Halo C １ ~C ６ Alkyl, C １ ~C ６ Alkoxy, and C ３ ~C ８ A compound or salt thereof according to any one of claims 1 to 11, which may be substituted with one or more groups independently selected from the group consisting of cycloalkyl groups. 2-[[(1S,4S,7S,13R,16S,19S,25S,33S,36S,42S,46S,51S)-42-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-6,13,18,35-tetramethyl-2,5,8,14,17,20,26,34,37,40,44-undecaoxo-36-(2-phenylethyl)-38-propyl-3,6,9,15,18,21,27,35,38,41,45-undecazahexacyclo[43.7.0.0 9,13 .0 21,25 .0 27,33 .0 46,51 ]dopentacontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propyl-33-prop-2-inyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,23S,28S,34S,37S,40S)-28-(2-azaspiro[3,3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(2-cyclohexylethyl)-3-cyclopentyl-37-cyclopropyl-34-[2-(3-fluoro Pyridine-4-yl)ethyl]-23-methoxy-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32-prop-2-enyl-38-propyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-3-cyclopentyl-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-19-cyclobutyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-33-ethyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-27-ethyl-6,13,18,30-tetramethyl-31-(3-methylbutyl)-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,22S,25S,28S,34S,38S,43S)-34-(2-azaspiro[3,3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-25-cyclopropyl-28-[2- (3-Fluoropyridine-4-yl)ethyl]-6,13,18,21,22,27-Hexamethyl-2,5,8,14,17,20,23,26,29,32,36-Undekaoxo-24,30-Dipropyl-3,6,9,15,18,21,24,27,30,33,37-Undekazatetracyclo[35.7.0.0 9,13 .0 38,43 ]Tetratetracontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-33-(2,2-difluoroethyl)-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-33-(3-fluoropropyl)-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,43S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-19-cyclobutyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-6,13,18,30,43-pentamethyl-2,5,8,14,17,20,26,29,32,35,39-undekaoxo-31-(2-phenylethyl)-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undekazatetracyclo[38.4.0.0 9,13 .0 21,25 ]Tetratetracontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-3,18-bis[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-31-[2-(3-fluoropyridine-4-yl)ethyl]-4-[(1R)-1-methoxyethyl]-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-37-cyclopropyl-24-ethyl-28-(3-fluoro-3-methylazetidine-1-carbonyl)-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-15-(3-methylbutoxymethyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-15-(2-methylpropoxymethyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-16,24-diethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-34-[2-(3-flu Olopyridine-4-yl)ethyl]-3-[(1S)-1-methoxyethyl]-4,9,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-3-[(1S)-1-ethoxyethyl]-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-34-(3,3,3-trifluoropropyl)-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-37-cyclopropyl-3-[(1S)-1-ethoxyethyl]-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-15-(3-methylbutoxymethyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-16,24-diethyl-28-(3-fluoro-3-methylazetidine-1-carbonyl)-4,9,35-trimethyl-34-(2-methylpropoxymethyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-3,18-bis[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-34-(2,2,2-trifluoroethoxymethyl)-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,16,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,16,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9S,12S,16S,22S,25S,28S,31S,34S,37R)-6-[(2S)-butane-2-yl]-31-cyclohexyl-3-(cyclohexyloxymethyl)-25-cyclopropyl-12-ethyl-16-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,23,28,29,32,37-hexamethyl-2,5,8,14,18,21,24,27,30,33,36-undecaoxo-22-(2-phenylethyl)-20,26-dipropyl-1,4,7,13,17,20,23,26,29,32,35-undecazatricyclo[35.3.0.0 9,13 ]Tetracontan-34-yl]methoxy]-N-tert-butylacetamide, N-tert-butyl-2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-18,24-diethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxyacetamide, N-tert-butyl-2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-18-(2-methylpropyl)-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxyacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-3-cyclopentyl-37-cyclopropyl-28-(3,3-dimethylazetidine-1-carbonyl)-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(cycloheptyloxymethyl)-37-cyclopropyl-34-[2-(4-fluorophenyl)ethyl]-4,9,16,24,35-pentamethyl-2,5,8,14,17,20,26,30,33,36,39-undekaoxo-3-propane-2-yl-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undekazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-34-[2-(3-chloropyridine-4-yl)ethyl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-3,18-bis[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-fluoroazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-fluoro-3-methylazetidine-1-carbonyl)-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,22S,25S,28S,34S,38S,43S)-4-[(2S)-butane-2-yl]-7-(cycloheptyloxymethyl)-19-cyclohexyl-25-cyclopropyl-34-(3-ethylazetidine-1-carbonyl)-28-[2-(3-fluoropyridine-4-yl)ethyl]-6,13,18,21,22,27-hexamethyl-2,5,8,14,17,20,23,26,29,32,36-undecaoxo-24,30-dipropyl-3,6,9,15,18,21,24,27,30,33,37-undecazatetracyclo[35.7.0.0 9,13 .0 38,43 ]Tetratetracontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-31-[2-(3-chloropyridine-4-yl)ethyl]-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-19-cyclohexyl-7-(cyclopentyloxymethyl)-28-cyclopropyl-27-ethyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-31-[2-(3-chloropyridine-4-yl)ethyl]-19-cyclobutyl-7-(2-cyclohexylethyl)-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-4-[(2S)-butane-2-yl]-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-37-(3,3-difluoropyrrolidine-1-carbonyl)-27-ethyl-31-[2-(2-fluorophenyl)ethyl]-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S)-4-[(2S)-butane-2-yl]-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-37-(3-ethyl-3-fluoroazetidine-1-carbonyl)-31-[2-(3-fluoropyridine-4-yl)ethyl]-6,13,18,30,42,42-hexamethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-43-oxa-3,6,9,15,18,21,27,30,33,36,40-undecazatetracyclo[38.4.0.0 9,13 .0 21,25 ]Tetratetracontan-16-yl]methoxy-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-28-(3,3-dimethylpyrrolidine-1-carbonyl)-24-ethyl-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-19-cyclohexyl-7-(cyclohexyloxymethyl)-28-cyclopropyl-31-[2-(3-fluoropyridine-4-yl)ethyl]-6,18,30-trimethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-fluoro-3-methylazetidine-1-carbonyl)-4,9,16,35-tetramethyl-34-[2-(1-methylcyclopropyl)ethyl]-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-4-[(2S)-butane-2-yl]-7-(cycloheptyloxymethyl)-19-cyclohexyl-28-cyclopropyl-37-(3-ethyl-3-fluoroazetidine-1-carbonyl)-31-[2-(3-fluoropyridine-4-yl)ethyl]-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(5-azaspiro[2,4]heptane-5-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclobutyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(6-azaspiro[3.4]octane-6-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclobutyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-28-(2,2-dimethylazetidine-1-carbonyl)-24-ethyl-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.4]octane-2-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(3-azabicyclo[3.2.0]heptane-3-carbonyl)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-18-[(2S)-butane-2-yl]-3-cyclohexyl-15-(cyclohexyloxymethyl)-37-cyclopropyl-24-ethyl-28-(3-ethyl-3-methylazetidine-1-carbonyl)-34-[2-(3-fluoropyridine-4-yl)ethyl]-4,9,16,35-tetramethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9R,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-3-cyclopentyl-37-cyclopropyl-9,24-diethyl-4,16,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(3S,6S,9S,15S,18S,21S,24S,28S,34S,37S,40S)-28-(2-azaspiro[3.3]heptane-2-carbonyl)-18-[(2S)-butane-2-yl]-15-(cyclohexyloxymethyl)-3-cyclopentyl-37-cyclopropyl-9-(2,2-difluoroethyl)-24-ethyl-4,16,35-trimethyl-2,5,8,14,17,20,26,30,33,36,39-undecaoxo-34-(2-phenylethyl)-32,38-dipropyl-1,4,7,13,16,19,25,29,32,35,38-undecazatetracyclo[38.3.0.0 9,13 .0 21,25 ]tritetracontan-6-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-27-(cyclopropylmethyl)-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [Heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-6,13,18,30-tetramethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27-propan-2-yl-33-propyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 [heptatetracontan-16-yl]methoxy]-N-tert-butylacetamide, and 2-[[(1S,4S,7S,13R,16S,19S,25S,28S,31S,37S,41S,46S)-37-(2-azaspiro[3.3]heptane-2-carbonyl)-4-[(2S)-butane-2-yl]-7-(cyclohexyloxymethyl)-19-cyclopentyl-28-cyclopropyl-6-(cyclopropylmethyl)-13,18,30-trimethyl-2,5,8,14,17,20,26,29,32,35,39-undecaoxo-31-(2-phenylethyl)-27,33-dipropyl-3,6,9,15,18,21,27,30,33,36,40-undecazapentacyclo[38.7.0.0 9,13 .0 21,25 .0 41,46 A compound selected from the group consisting of heptatetracontan-16-yl]methoxy-N-tert-butylacetamide or a salt thereof. 　 A compound or salt thereof according to any one of claims 1 to 13, which inhibits ALK. 　 A pharmaceutical composition comprising a compound or a salt thereof as described in any one of claims 1 to 14. 　 A pharmaceutical composition for treating and / or preventing cancer in a subject, comprising an effective amount of a compound or salt thereof according to any one of claims 1 to 14.

Images