JP2023084946A - Novel compound having bioactivity - Google Patents

Abstract

To provide a novel compound and applications thereof.SOLUTION: The present invention discloses a compound represented by formula I or an enantiomer thereof, or a salt thereof or a solvate thereof, and uses thereof. R1, R2, and R3 each represent one of substituents described herein or a combination thereof. The present invention also discloses a pharmaceutical composition for preventing or treating various diseases such as cancer including leukemia, preventive and therapeutic methods, and technical matter associated therewith.SELECTED DRAWING: None

Description

The present disclosure relates to novel fused tricyclic compounds or enantiomers thereof or pharmaceutically acceptable salts or solvates thereof that are useful as pharmaceuticals. More particularly, it relates to a pharmaceutical composition containing said fused tricyclic compound or its enantiomers or their pharmaceutically acceptable salts or their solvates. The present disclosure also relates to therapeutic agents containing the fused tricyclic compounds or enantiomers thereof or pharmaceutically acceptable salts or solvates thereof.

Various physiologically active substances are being developed. However, it remains difficult to develop compounds with the desired activity.

The present disclosure provides novel compounds, uses thereof, and the like.

As a result of intensive research by the present inventors, compounds represented by the following formula I or II and their related structural formulas, or pharmaceutically acceptable salts thereof (hereinafter referred to as "compounds of the present disclosure" or "the present The inventors have found that the compound(s) of the disclosure, sometimes referred to as "the compound(s) of the disclosure," solve the above problems, and have completed the technical matter of the present disclosure. That is, the present disclosure is as follows.

This disclosure provides the following items.

により表される化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物であって、式中、
Ｒ_１は、
必要に応じて置換されたアルキル、
必要に応じて置換されたアルケニル、
必要に応じて置換されたアルキニル、
必要に応じて置換されたシクロアルキル、
必要に応じて置換されたヘテロシクロアルキル、
必要に応じて置換されたアリール、
必要に応じて置換されたヘテロアリール、または
必要に応じて置換されたカルボニルであり、
Ｒ_２およびＲ_３は各々独立して、
水素、
必要に応じて置換されたアルキル、
必要に応じて置換されたシクロアルキル、
必要に応じて置換されたヘテロシクロアルキル、
必要に応じて置換されたアリール、または
必要に応じて置換されたヘテロアリールである、
化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目２）
式ＩＩ：

により表される化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物であって、式中、
Ｒ_１は、
必要に応じて置換されたアルキル、
必要に応じて置換されたアルケニル、
必要に応じて置換されたアルキニル、
必要に応じて置換されたシクロアルキル、
必要に応じて置換されたヘテロシクロアルキル、
必要に応じて置換されたアリール、
必要に応じて置換されたヘテロアリール、または
必要に応じて置換されたカルボニルであり、
Ｒ_２およびＲ_３は各々独立して、
水素、
必要に応じて置換されたアルキル、
必要に応じて置換されたシクロアルキル、
必要に応じて置換されたヘテロシクロアルキル、
必要に応じて置換されたアリール、または
必要に応じて置換されたヘテロアリールである、
化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目３）
Ｒ_１の前記アルキル、アルケニル、アルキニル、シクロアルキル、ヘテロシクロアルキル、アリール、ヘテロアリール、およびカルボニルは各々独立して、置換基群Ｉから選択される１個から最大置換可能数までの同一または異なる置換基で必要に応じて置換されている、
先行する項目に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目４）
Ｒ_２およびＲ_３の前記アルキル、シクロアルキル、ヘテロシクロアルキル、アリールおよびヘテロアリールは各々独立して、置換基群Ｉから選択される１個から最大置換可能数までの同一または異なる置換基で必要に応じて置換されている、
先行する項目に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目５）
Ｒ_１は、
必要に応じて置換されたアルキル、
必要に応じて置換されたシクロアルキルアルキル、
必要に応じて置換されたヘテロシクロアルキルアルキル、
必要に応じて置換されたアリールアルキル、
必要に応じて置換されたヘテロアリールアルキル、
必要に応じて置換されたカルボキシアルキル、
必要に応じて置換されたカルバモイルアルキル、
必要に応じて置換されたアミノアルキル、
必要に応じて置換されたアルケニル、
必要に応じて置換されたアルキニル、
必要に応じて置換されたシクロアルキル、
必要に応じて置換されたヘテロシクロアルキル、
必要に応じて置換されたアリール、
必要に応じて置換されたヘテロアリール、
必要に応じて置換されたカルボニル、
必要に応じて置換されたアルキルカルボニル、
必要に応じて置換されたアルケニルカルボニル、
必要に応じて置換されたシクロアルキルカルボニル、
必要に応じて置換されたアリールカルボニル、
必要に応じて置換されたカルボキシ、または
必要に応じて置換されたカルバモイルであり、
ここで、Ｒ_１の上記基は、置換基群ＩＩから選択される１個から最大置換可能数までの同一または異なる置換基で必要に応じて置換される、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目６）
Ｒ_２およびＲ_３は各々独立して、
必要に応じて置換されたアルキル、
必要に応じて置換されたシクロアルキルアルキル、
必要に応じて置換されたアリールアルキル、
必要に応じて置換されたヘテロアリールアルキル、
必要に応じて置換されたカルボニルアルキル、
必要に応じて置換されたカルボキシアルキル、
必要に応じて置換されたカルバモイルアルキル、
必要に応じて置換されたアミノアルキル、
必要に応じて置換されたシクロアルキル、
必要に応じて置換されたヘテロシクロアルキル、
必要に応じて置換されたアリール、または
必要に応じて置換されたヘテロアリールであり、
ここで、Ｒ_２、およびＲ_３の上記基は、置換基群ＩＩから選択される１個から最大置換可能数までの同一または異なる置換基で必要に応じて置換される、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目７）
Ｒ_１は、
アルキル、
シクロアルキル、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、置換カルバモイル、アミノおよび置換アミノからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアルキル、
アルケニル、
アルキニル、
シクロアルキル、
ヘテロシクロアルキル、
アリール、
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているアリール、
ヘテロアリール、
シクロアルキル、アルケニル、およびアリールからなる群より選択される置換基で置換されているカルボニル、
アルキルカルボニル、
ハロゲン、ヒドロキシ、シクロアルキル、アリール、置換アリール、ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、アミノ、置換アミノ、グアニジノおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアルキルカルボニル、
アルキル、および置換アルキルからなる群より選択される置換基で置換されているカルボキシ、または
アルキル、置換アルキル、置換シクロアルキル、およびアリールからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているカルバモイルであり、
ここで、置換ヘテロシクロアルキル、置換アリール、置換ヘテロアリール、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、置換基群ＩＩＩから選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目８）
Ｒ_２は、
アルキル、
シクロアルキル、アリール、置換アリール、ヘテロアリール、置換カルボニル、カルボキシ、置換カルボキシ、カルバモイル、置換カルバモイル、アミノ、置換アミノ、グアニジノ、ヒドロキシおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアルキル、
シクロアルキル、
ヘテロシクロアルキル、
アリール、
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているアリール、または
ヘテロアリールであり、
ここで、置換アリール、置換カルボニル、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、置換基群ＩＩＩから選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目９）
Ｒ_３は、
アルキル、
シクロアルキル、アリール、置換アリール、ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、置換カルバモイル、アミノ、置換アミノ、グアニジノ、ヒドロキシおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアルキル、
シクロアルキル、
ヘテロシクロアルキル、
アリール、または
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているアリールであり、
ここで、置換アリール、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、置換基群ＩＩＩから選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１０）
Ｒ_１は、
アルキル、
シクロアルキル、ヘテロシクロアルキル、置換ヘテロシクロアルキル、アリール、置換アリール、ヘテロアリール、置換ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、置換カルバモイル、アミノおよび置換アミノからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアルキル、
アルケニル、
アルキニル、
シクロアルキル、
ヘテロシクロアルキル、
アリール、
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているアリール、
ヘテロアリール、
シクロアルキル、アルケニル、およびアリールからなる群より選択される置換基で置換されているカルボニル、
アルキルカルボニル、
ハロゲン、ヒドロキシ、シクロアルキル、アリール、置換アリール、ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、アミノ、置換アミノ、グアニジノおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアルキルカルボニル、
アルキル、および置換アルキルからなる群より選択される置換基で置換されているカルボキシ、または
アルキル、置換アルキル、シクロアルキル、およびアリールからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているカルバモイルであり、
ここで、置換ヘテロシクロアルキル、置換アリール、置換ヘテロアリール、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、ハロゲン、アルキル、ヒドロキシ、アルコキシ、アリール、ｔｅｒｔ－ブトキシカルボニル基、およびｔｅｒｔ－ブチルジメチルシリル基から選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１１）
Ｒ_２は、
アルキル、
シクロアルキル、アリール、置換アリール、ヘテロアリール、置換カルボニル、カルボキシ、置換カルボキシ、カルバモイル、置換カルバモイル、アミノ、置換アミノ、グアニジノ、ヒドロキシおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアルキル、
シクロアルキル、
ヘテロシクロアルキル
アリール、
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているアリール、または
ヘテロアリールであり、
ここで、置換アリール、置換カルボニル、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、ハロゲン、アルキル、ヘテロシクリル、ヒドロキシおよびアルコキシから選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１２）
Ｒ_３は、
アルキル、
シクロアルキル、アリール、置換アリール、ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、置換カルバモイル、アミノ、置換アミノ、グアニジノ、ヒドロキシおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアルキル、
シクロアルキル、
ヘテロシクロアルキル、
アリール、または
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているアリールであり、
ここで、置換アリール、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、ハロゲン、アルキル、ヒドロキシおよびアルコキシから選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１３）
Ｒ_１は、
Ｃ_１－６アルキル、
Ｃ_３－１０シクロアルキル、Ｃ_３－１０ヘテロシクロアルキル、置換Ｃ_３－１０ヘテロシクロアルキル、Ｃ_３－１０アリール、置換Ｃ_３－１０アリール、Ｃ_３－１０ヘテロアリール、置換Ｃ_３－１０ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、アミノおよび置換アミノからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_１－６アルキル、
Ｃ_２－６アルケニル、
Ｃ_２－６アルキニル、
Ｃ_３－１０シクロアルキル、
Ｃ_３－１０ヘテロシクロアルキル、
Ｃ_３－１０アリール、
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリール、
Ｃ_３－１０ヘテロアリール、
Ｃ_３－１０シクロアルキル、Ｃ_２－６アルケニル、およびＣ_３－１０アリールからなる群より選択される置換基で置換されているカルボニル、
Ｃ_１－６アルキルカルボニル、
ハロゲン、ヒドロキシ、Ｃ_３－１０シクロアルキル、Ｃ_３－１０アリール、置換Ｃ_３－１０アリール、Ｃ_３－１０ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、アミノ、置換アミノ、グアニジノおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_１－６アルキルカルボニル、
Ｃ_１－６アルキル、および置換Ｃ_１－６アルキルからなる群より選択される置換基で置換されているカルボキシ、または
Ｃ_１－６アルキル、置換Ｃ_１－６アルキル、Ｃ_３－１０シクロアルキル、およびＣ_３－１０アリールからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているカルバモイルであり、
ここで、置換Ｃ_３－１０ヘテロシクロアルキル、置換Ｃ_３－１０アリール、置換Ｃ_３－１０ヘテロアリール、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、ハロゲン、Ｃ_１－６アルキル、ヒドロキシ、Ｃ_１－６アルコキシ、Ｃ_３－１０アリール、ｔｅｒｔ－ブトキシカルボニル基、およびｔｅｒｔ－ブチルジメチルシリル基から選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１４）
Ｒ_２は、
Ｃ_１－６アルキル、
Ｃ_３－１０シクロアルキル、Ｃ_３－１０アリール、置換Ｃ_３－１０アリール、Ｃ_３－１０ヘテロアリール、置換カルボニル、カルボキシ、置換カルボキシ、カルバモイル、置換カルバモイル、アミノ、置換アミノ、グアニジノ、ヒドロキシおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_１－６アルキル、
Ｃ_３－１０シクロアルキル、
Ｃ_３－１０ヘテロシクロアルキル
Ｃ_３－１０アリール、
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリール、または
Ｃ_３－１０ヘテロアリールであり、
ここで、置換Ｃ_３－１０アリール、置換カルボニル、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、ハロゲン、アルキル、ヘテロシクリル、ヒドロキシおよびＣ_１－６アルコキシから選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１５）
Ｒ_３は、
Ｃ_１－６アルキル、
Ｃ_３－１０シクロアルキル、Ｃ_３－１０アリール、置換Ｃ_３－１０アリール、Ｃ_３－１０ヘテロアリール、カルボキシ、置換カルボキシ、カルバモイル、置換カルバモイル、アミノ、置換アミノ、グアニジノ、ヒドロキシおよび置換オキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_１－６アルキル、
Ｃ_３－１０シクロアルキル、
Ｃ_３－１０ヘテロシクロアルキル、
Ｃ_３－１０アリール、または
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリールであり、
ここで、置換Ｃ_３－１０アリール、置換Ｃ_３－１０ヘテロアリール、置換カルボキシ、置換カルバモイル、置換アミノ、および置換オキシは各々独立して、ハロゲン、Ｃ_１－６アルキル、ヒドロキシおよびＣ_１－６アルコキシから選択される１個から最大置換可能数までの同一または異なる置換基を有する、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１６）
Ｒ_１は、
Ｃ_１－６アルキル、
Ｃ_３－１０シクロアルキルＣ_１－６アルキル、
Ｃ_３－１０ヘテロシクロアルキルＣ_１－６アルキル、
Ｃ_１－６アルキルおよびｔｅｒｔ－ブトキシカルボニル基からなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０ヘテロシクロアルキルＣ_１－６アルキル、
Ｃ_３－１０アリールＣ_１－６アルキル、
Ｃ_１－６アルキル、ハロゲン、ヒドロキシおよびＣ_１－６アルコキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリールＣ_１－６アルキル、
Ｃ_３－１０ヘテロアリールＣ_１－６アルキル、
ｔｅｒｔ－ブトキシカルボニル基で１個から最大置換可能数置換されているＣ_３－１０ヘテロアリールＣ_１－６アルキル、
カルボキシＣ_１－６アルキル、
Ｃ_１－６アルキルで置換されているカルボキシＣ_１－６アルキル、
カルバモイルＣ_１－６アルキル、
アミノＣ_１－６アルキル、
Ｃ_１－６アルキルで１個から最大置換可能数までの同一または異なる置換基で置換されているアミノＣ_１－６アルキル、
Ｃ_２－６アルケニル、
Ｃ_２－６アルキニル、
Ｃ_３－１０シクロアルキル、
Ｃ_３－１０ヘテロシクロアルキル、
Ｃ_３－１０アリール、
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリール、
Ｃ_３－１０ヘテロアリール、
Ｃ_３－１０シクロアルキル、Ｃ_２－６アルケニル、およびＣ_３－１０アリールからなる群より選択される置換基で置換されているカルボニル、
Ｃ_１－６アルキルカルボニル、
ハロゲン、ヒドロキシ、Ｃ_１－６アルコキシ、Ｃ_３－１０シクロアルキル、Ｃ_３－１０ヘテロアリール、カルボキシ、Ｃ_１－６アルキルカルボキシ、カルバモイル、アミノ、ｔｅｒｔ－ブトキシカルボニルアミノおよびグアニジノからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_１－６アルキルカルボニル、
Ｃ_３－１０アリールＣ_１－６アルキルカルボニル、
ハロゲン、ヒドロキシおよびＣ_１－６アルコキからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリールＣ_１－６アルキルカルボニル、
Ｃ_１－６アルキル、およびＣ_３－１０アリールＣ_１－６アルキルからなる群より選択される置換基で置換されているカルボキシ、または
Ｃ_１－６アルキル、Ｃ_３－１０アリールＣ_１－６アルキル、Ｃ_３－１０シクロアルキル、およびＣ_３－１０アリールからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているカルバモイルであり、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１７）
Ｒ_１は、
Ｃ_３－１０シクロアルキル、Ｃ_２－６アルケニル、およびＣ_３－１０アリールからなる群より選択される置換基で置換されているカルボニル、
Ｃ_１－６アルキルカルボニル、
ハロゲン、ヒドロキシ、Ｃ_１－６アルコキシ、Ｃ_３－１０シクロアルキル、Ｃ_３－１０ヘテロアリール、カルボキシ、Ｃ_１－６アルキルカルボキシ、カルバモイル、アミノ、ｔｅｒｔ－ブトキシカルボニルアミノおよびグアニジノからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_１－６アルキルカルボニル、
Ｃ_３－１０アリールＣ_１－６アルキルカルボニル、
ハロゲン、ヒドロキシおよびＣ_１－６アルコキからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリールＣ_１－６アルキルカルボニル、
Ｃ_１－６アルキル、およびＣ_３－１０アリールＣ_１－６アルキルからなる群より選択される置換基で置換されているカルボキシ、または
Ｃ_１－６アルキル、Ｃ_３－１０アリールＣ_１－６アルキル、Ｃ_３－１０シクロアルキル、およびＣ_３－１０アリールからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているカルバモイルであり、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１８）
Ｒ_２は、
Ｃ_１－６アルキル、
Ｃ_３－１０シクロアルキル、Ｃ_３－１０ヘテロアリール、ピロリジンカルボニル、グアニジノ、ヒドロキシおよびＣ_１－６アルコキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_１－６アルキル、
Ｃ_３－１０アリールＣ_１－６アルキル、
ハロゲン、ヒドロキシおよびＣ_１－６アルコキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリールＣ_１－６アルキル、
カルボキシＣ_１－６アルキル、
Ｃ_１－６アルキルで置換されているカルボキシＣ_１－６アルキル、
カルバモイルＣ_１－６アルキル、
Ｃ_１－６アルキルで１個から最大置換可能数までの同一または異なる置換基で置換されているカルバモイルＣ_１－６アルキル、
アミノＣ_１－６アルキル、
Ｃ_１－６アルキルおよびｔｅｒｔ－ブトキシカルボニルからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアミノＣ_１－６アルキル、
Ｃ_３－１０シクロアルキル、
Ｃ_３－１０ヘテロシクロアルキル
Ｃ_３－１０アリール、
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリール、または
Ｃ_３－１０ヘテロアリールである、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目１９）
Ｒ_３は、
Ｃ_１－６アルキル、
Ｃ_３－１０シクロアルキル、Ｃ_３－１０ヘテロアリール、グアニジノ、ヒドロキシおよびＣ_１－６アルコキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_１－６アルキル、
Ｃ_３－１０アリールＣ_１－６アルキル、
ハロゲン、ヒドロキシおよびＣ_１－６アルコキシからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリールＣ_１－６アルキル、
カルボキシＣ_１－６アルキル、
Ｃ_１－６アルキルで置換されているカルボキシＣ_１－６アルキル、
カルバモイルＣ_１－６アルキル、
Ｃ_１－６アルキルで１個から最大置換可能数までの同一または異なる置換基で置換されているカルバモイルＣ_１－６アルキル、
アミノＣ_１－６アルキル、
Ｃ_１－６アルキルおよびｔｅｒｔ－ブトキシカルボニルからなる群より選択される１個から最大置換可能数までの同一または異なる置換基で置換されているアミノＣ_１－６アルキル、
Ｃ_３－１０シクロアルキル、
Ｃ_３－１０ヘテロシクロアルキル
Ｃ_３－１０アリール、または
ハロゲンで１個から最大置換可能数までの同一または異なる置換基で置換されているＣ_３－１０アリールである、
先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目２０）
Ｒ_１が、下記表、

から選択される、先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目２１）
Ｒ_２が、下記表、

から選択される、先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目２２）
Ｒ_３が、下記表、

から選択される、先行する項目のいずれか一項に記載の化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物。
（項目２３）
先行する項目のいずれか一項に記載の化合物またはその薬学的に許容される塩を含有する、抗がん剤。
（項目２４）
先行する項目のいずれか一項に記載の化合物またはその薬学的に許容される塩を含有する医薬。
（項目２５）
がんの予防薬または治療薬である先行する項目に記載の医薬。
（項目２６）
先行する項目のいずれか一項に記載の化合物またはその薬学的に許容される塩及び薬学的に許容される担体を含有する医薬組成物。
（項目２７）
先行する項目のいずれか一項に記載の化合物またはその薬学的に許容される塩及び薬学的に許容される担体を含有する、がんを予防または治療するための医薬組成物。
（項目２８）
前記がんが、白血病を含む、先行する項目に記載の医薬または医薬組成物。 (Item 1)
Formula I:

A compound represented by or an enantiomer thereof or a salt thereof or a solvate thereof, wherein
_R1 is
optionally substituted alkyl,
optionally substituted alkenyl,
optionally substituted alkynyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl,
optionally substituted heteroaryl, or optionally substituted carbonyl,
R ₂ and R ₃ are each independently
hydrogen,
optionally substituted alkyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl, or optionally substituted heteroaryl,
A compound or its enantiomers or their salts or their solvates.
(Item 2)
Formula II:

A compound represented by or an enantiomer thereof or a salt thereof or a solvate thereof, wherein
_R1 is
optionally substituted alkyl,
optionally substituted alkenyl,
optionally substituted alkynyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl,
optionally substituted heteroaryl, or optionally substituted carbonyl,
R ₂ and R ₃ are each independently
hydrogen,
optionally substituted alkyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl, or optionally substituted heteroaryl,
A compound or its enantiomers or their salts or their solvates.
(Item 3)
The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl and carbonyl of R ₁ are each independently selected from Substituent Group I and are the same or different from 1 to the maximum substitutable number. optionally substituted with substituents,
A compound or an enantiomer thereof or a salt or solvate thereof according to the preceding item.
(Item 4)
Each of said alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl of R ₂ and R ₃ is independently required from 1 to the maximum substitutable number of the same or different substituents selected from Substituent Group I. are replaced according to the
A compound or an enantiomer thereof or a salt or solvate thereof according to the preceding item.
(Item 5)
_R1 is
optionally substituted alkyl,
optionally substituted cycloalkylalkyl,
optionally substituted heterocycloalkylalkyl,
optionally substituted arylalkyl,
optionally substituted heteroarylalkyl,
optionally substituted carboxyalkyl,
optionally substituted carbamoylalkyl,
optionally substituted aminoalkyl,
optionally substituted alkenyl,
optionally substituted alkynyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl,
optionally substituted heteroaryl,
optionally substituted carbonyl,
optionally substituted alkylcarbonyl,
optionally substituted alkenylcarbonyl,
optionally substituted cycloalkylcarbonyl,
optionally substituted arylcarbonyl,
optionally substituted carboxy, or optionally substituted carbamoyl,
wherein the above groups for R ₁ are optionally substituted with 1 to the maximum substitutable number of the same or different substituents selected from Substituent Group II,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 6)
R ₂ and R ₃ are each independently
optionally substituted alkyl,
optionally substituted cycloalkylalkyl,
optionally substituted arylalkyl,
optionally substituted heteroarylalkyl,
optionally substituted carbonylalkyl,
optionally substituted carboxyalkyl,
optionally substituted carbamoylalkyl,
optionally substituted aminoalkyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl, or optionally substituted heteroaryl,
wherein the above groups for R ₂ and R ₃ are optionally substituted with the same or different substituents from 1 to the maximum substitutable number selected from Substituent Group II,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 7)
_R1 is
alkyl,
one up to maximum substitution selected from the group consisting of cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino and substituted amino alkyl substituted with up to the possible number of identical or different substituents;
alkenyl,
alkynyl,
cycloalkyl,
heterocycloalkyl,
Aryl,
aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
heteroaryl,
carbonyl substituted with a substituent selected from the group consisting of cycloalkyl, alkenyl, and aryl;
alkylcarbonyl,
halogen, hydroxy, cycloalkyl, aryl, substituted aryl, heteroaryl, carboxy, substituted carboxy, carbamoyl, amino, substituted amino, guanidino and substituted oxy, identical or different from one to the maximum possible number of substitutions alkylcarbonyl substituted with a substituent,
carboxy substituted with a substituent selected from the group consisting of alkyl and substituted alkyl, or the same from 1 to the maximum number of possible substitutions selected from the group consisting of alkyl, substituted alkyl, substituted cycloalkyl, and aryl or carbamoyl substituted with different substituents,
Here, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently selected from Substituent Group III, and having identical or different substituents,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 8)
_R2 is
alkyl,
cycloalkyl, aryl, substituted aryl, heteroaryl, substituted carbonyl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy, from one to the maximum possible number of substitutions alkyl substituted with the same or different substituents of
cycloalkyl,
heterocycloalkyl,
Aryl,
aryl or heteroaryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
Here, substituted aryl, substituted carbonyl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently the same or different substituents selected from Substituent Group III up to the maximum substitutable number. have
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 9)
_R3 is
alkyl,
cycloalkyl, aryl, substituted aryl, heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy, identical or alkyl substituted with different substituents,
cycloalkyl,
heterocycloalkyl,
aryl or aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
wherein substituted aryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy each independently have the same or different substituents selected from Substituent Group III up to the maximum possible number of substituents;
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 10)
_R1 is
alkyl,
one up to maximum substitution selected from the group consisting of cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino and substituted amino alkyl substituted with up to the possible number of identical or different substituents;
alkenyl,
alkynyl,
cycloalkyl,
heterocycloalkyl,
Aryl,
aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
heteroaryl,
carbonyl substituted with a substituent selected from the group consisting of cycloalkyl, alkenyl, and aryl;
alkylcarbonyl,
halogen, hydroxy, cycloalkyl, aryl, substituted aryl, heteroaryl, carboxy, substituted carboxy, carbamoyl, amino, substituted amino, guanidino and substituted oxy, identical or different from one to the maximum possible number of substitutions alkylcarbonyl substituted with a substituent,
carboxy substituted with a substituent selected from the group consisting of alkyl and substituted alkyl; carbamoyl substituted with different substituents,
wherein substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently halogen, alkyl, hydroxy, alkoxy, aryl, tert-butoxycarbonyl groups, and having the same or different substituents from 1 to the maximum substitutable number selected from tert-butyldimethylsilyl groups,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 11)
_R2 is
alkyl,
cycloalkyl, aryl, substituted aryl, heteroaryl, substituted carbonyl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy, from one to the maximum possible number of substitutions alkyl substituted with the same or different substituents of
cycloalkyl,
heterocycloalkylaryl,
aryl or heteroaryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
wherein substituted aryl, substituted carbonyl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently identical from one to the maximum possible number of substitutions selected from halogen, alkyl, heterocyclyl, hydroxy and alkoxy; or with different substituents,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 12)
_R3 is
alkyl,
cycloalkyl, aryl, substituted aryl, heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy, identical or alkyl substituted with different substituents,
cycloalkyl,
heterocycloalkyl,
aryl or aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
wherein substituted aryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy each independently represent from one to the maximum possible number of the same or different substituents selected from halogen, alkyl, hydroxy and alkoxy; have
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 13)
_R1 is
C _1-6 alkyl,
C _3-10 cycloalkyl, C _3-10 heterocycloalkyl, substituted C _3-10 heterocycloalkyl, C _3-10 aryl, substituted C _3-10 aryl, C _3-10 heteroaryl, substituted C _3-10 hetero C _1-6 alkyl substituted with the same or different substituents from 1 to the maximum possible number of substituents selected from the group consisting of aryl, carboxy, substituted carboxy, carbamoyl, amino and substituted amino;
C _2-6 alkenyl,
C _2-6 alkynyl,
C _3-10 cycloalkyl,
C _3-10 heterocycloalkyl,
C _3-10 aryl,
C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
C _3-10 heteroaryl,
carbonyl substituted with a substituent selected from the group consisting of C _3-10 cycloalkyl, C _2-6 alkenyl, and C _3-10 aryl;
C _1-6 alkylcarbonyl,
the group consisting of halogen, hydroxy, C _3-10 cycloalkyl, C _3-10 aryl, substituted C _3-10 aryl, C _3-10 heteroaryl, carboxy, substituted carboxy, carbamoyl, amino, substituted amino, guanidino and substituted oxy C _1-6 alkylcarbonyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from
C _1-6 alkyl, and carboxy substituted with a substituent selected from the group consisting of C _1-6 alkyl, or C _1-6 alkyl, substituted C _1-6 alkyl, C _3-10 cycloalkyl, and C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents,
wherein substituted C _3-10 heterocycloalkyl, substituted C _3-10 aryl, substituted C _3-10 heteroaryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently halogen, C _{1- 6} alkyl, hydroxy, C _1-6 alkoxy, C _3-10 aryl, tert-butoxycarbonyl group, and tert-butyldimethylsilyl group having the same or different substituents from 1 to the maximum possible number of substituents ,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 14)
_R2 is
C _1-6 alkyl,
C _3-10 cycloalkyl, C _3-10 aryl, substituted C _3-10 aryl, C _3-10 heteroaryl, substituted carbonyl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted C _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of oxy,
C _3-10 cycloalkyl,
C _3-10 heterocycloalkylC _3-10 aryl,
C _3-10 aryl or C _3-10 heteroaryl substituted with from 1 to the maximum possible number of substituents by halogen with the same or different substituents;
wherein substituted C _3-10 aryl, substituted carbonyl, substituted carboxy, substituted carbamoyl, substituted amino and substituted oxy are each independently one selected from halogen, alkyl, heterocyclyl, hydroxy and C _1-6 alkoxy with the same or different substituents from to the maximum possible number of substituents,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 15)
_R3 is
C _1-6 alkyl,
consisting of C _3-10 cycloalkyl, C _3-10 aryl, substituted C _3-10 aryl, C _3-10 heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy C _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group,
C _3-10 cycloalkyl,
C _3-10 heterocycloalkyl,
C _3-10 aryl, or C _3-10 aryl substituted with from 1 to the maximum possible number of substituents with the same or different substituents with halogen;
wherein substituted C _3-10 aryl, substituted C _3-10 heteroaryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently halogen, C _1-6 alkyl, hydroxy and C _1-6 having the same or different substituents from 1 to the maximum possible number of substituents selected from alkoxy;
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 16)
_R1 is
C _1-6 alkyl,
C _3-10 cycloalkyl C _1-6 alkyl,
C _3-10 heterocycloalkyl C _1-6 alkyl,
C _3-10 heterocycloalkylC _1-6 alkyl substituted with from 1 to the maximum possible number of the same or different substituents selected from the group consisting of C _1-6 alkyl and tert-butoxycarbonyl group,
C _3-10 aryl C _1-6 alkyl,
C _3-10 arylC 1-6 substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of C _1-6 alkyl, halogen, hydroxy _{and C 1-6 alkoxy} alkyl,
C _3-10 heteroaryl C _1-6 alkyl,
C _3-10 heteroaryl C _1-6 alkyl substituted from one to the maximum possible number of substitutions with a tert-butoxycarbonyl group,
carboxyC _1-6 alkyl,
carboxyC _1-6 alkyl substituted with C _1-6 alkyl,
carbamoyl C _1-6 alkyl,
amino C _1-6 alkyl,
aminoC _1-6 alkyl substituted with from 1 to the maximum possible number of substituents on C _1-6 alkyl with the same or different substituents;
C _2-6 alkenyl,
C _2-6 alkynyl,
C _3-10 cycloalkyl,
C _3-10 heterocycloalkyl,
C _3-10 aryl,
C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
C _3-10 heteroaryl,
carbonyl substituted with a substituent selected from the group consisting of C _3-10 cycloalkyl, C _2-6 alkenyl, and C _3-10 aryl;
C _1-6 alkylcarbonyl,
selected from the group consisting of halogen, hydroxy, C _1-6 alkoxy, C _3-10 cycloalkyl, C _3-10 heteroaryl, carboxy, C _1-6 alkylcarboxy, carbamoyl, amino, tert-butoxycarbonylamino and guanidino C _1-6 alkylcarbonyl substituted with the same or different substituents from 1 to the maximum substitutable number of
C _3-10 aryl C _1-6 alkylcarbonyl,
C _3-10 arylC _1-6 alkylcarbonyl substituted with from 1 to the maximum substitutable number of the same or different substituents selected from the group consisting of halogen, hydroxy and C _1-6 alkoxy;
carboxy substituted with a substituent selected from the group consisting of C _1-6 alkyl, and C _3-10 arylC _1-6 alkyl, or C _1-6 alkyl, C _3-10 arylC _1-6 alkyl , C _3-10 cycloalkyl, and C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 17)
_R1 is
carbonyl substituted with a substituent selected from the group consisting of C _3-10 cycloalkyl, C _2-6 alkenyl, and C _3-10 aryl;
C _1-6 alkylcarbonyl,
selected from the group consisting of halogen, hydroxy, C _1-6 alkoxy, C _3-10 cycloalkyl, C _3-10 heteroaryl, carboxy, C _1-6 alkylcarboxy, carbamoyl, amino, tert-butoxycarbonylamino and guanidino C _1-6 alkylcarbonyl substituted with the same or different substituents from 1 to the maximum substitutable number of
C _3-10 aryl C _1-6 alkylcarbonyl,
C _3-10 arylC _1-6 alkylcarbonyl substituted with from 1 to the maximum substitutable number of the same or different substituents selected from the group consisting of halogen, hydroxy and C _1-6 alkoxy;
carboxy substituted with a substituent selected from the group consisting of C _1-6 alkyl, and C _3-10 arylC _1-6 alkyl, or C _1-6 alkyl, C _3-10 arylC _1-6 alkyl , C _3-10 cycloalkyl, and C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents,
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 18)
_R2 is
C _1-6 alkyl,
substituted with from 1 to the maximum possible number of the same or different substituents selected from the group consisting of C _3-10 cycloalkyl, C _3-10 heteroaryl, pyrrolidinecarbonyl, guanidino, hydroxy and C _1-6 alkoxy; C _1-6 alkyl,
C _3-10 aryl C _1-6 alkyl,
C _3-10 arylC _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of halogen, hydroxy and C _1-6 alkoxy;
carboxyC _1-6 alkyl,
carboxyC _1-6 alkyl substituted with C _1-6 alkyl,
carbamoyl C _1-6 alkyl,
carbamoylC _1-6 alkyl substituted with from 1 to the maximum possible number of substituents on C _1-6 alkyl with the same or different substituents;
amino C _1-6 alkyl,
aminoC _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of C _1-6 alkyl and tert-butoxycarbonyl;
C _3-10 cycloalkyl,
C _3-10 heterocycloalkylC _3-10 aryl,
C _3-10 aryl or C _3-10 heteroaryl substituted with from 1 to the maximum possible number of substituents with the same or different substituents with halogen;
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 19)
_R3 is
C _1-6 alkyl,
C substituted with one to the maximum substitutable number of the same or different substituents selected from the group consisting of C _3-10 cycloalkyl, C _3-10 heteroaryl, guanidino, hydroxy and C _1-6 alkoxy; _1-6 alkyl,
C _3-10 aryl C _1-6 alkyl,
C _3-10 arylC _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of halogen, hydroxy and C _1-6 alkoxy;
carboxyC _1-6 alkyl,
carboxyC _1-6 alkyl substituted with C _1-6 alkyl,
carbamoyl C _1-6 alkyl,
carbamoylC _1-6 alkyl substituted with from 1 to the maximum possible number of substituents on C _1-6 alkyl with the same or different substituents;
amino C _1-6 alkyl,
aminoC _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of C _1-6 alkyl and tert-butoxycarbonyl;
C _3-10 cycloalkyl,
C _3-10 heterocycloalkyl C _3-10 aryl, or C _3-10 aryl substituted with from 1 to the maximum possible number of substituents with the same or different substituents with halogen;
A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof.
(Item 20)
R ₁ is the following table,

A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof selected from:
(Item 21)
R ₂ is represented in the table below,

A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof selected from:
(Item 22)
R ₃ is the following table,

A compound according to any one of the preceding items or an enantiomer thereof or a salt or solvate thereof selected from:
(Item 23)
An anticancer agent comprising the compound or a pharmaceutically acceptable salt thereof according to any one of the preceding items.
(Item 24)
A medicament containing a compound or a pharmaceutically acceptable salt thereof according to any one of the preceding items.
(Item 25)
The drug according to the preceding item, which is a cancer prophylactic or therapeutic drug.
(Item 26)
A pharmaceutical composition comprising a compound according to any one of the preceding items or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
(Item 27)
A pharmaceutical composition for preventing or treating cancer, comprising the compound or a pharmaceutically acceptable salt thereof according to any one of the preceding items and a pharmaceutically acceptable carrier.
(Item 28)
A medicament or pharmaceutical composition according to the preceding item, wherein said cancer comprises leukemia.

It is contemplated in the present disclosure that one or more of the above features may be provided in further combinations in addition to the explicit combination. Still further embodiments and advantages of the present disclosure will be appreciated by those skilled in the art upon reading and understanding the following detailed description, if necessary.

The compounds of the present disclosure exhibit excellent anticancer activity against cancer, especially leukemia. Therefore, the compounds of the present disclosure are useful as therapeutic and/or prophylactic agents for cancer.

The present disclosure is described in further detail below. It should be understood that throughout this specification, expressions in the singular also include the concept of the plural unless specifically stated otherwise. Thus, articles in the singular (eg, “a,” “an,” “the,” etc. in the English language) should be understood to include their plural forms as well, unless otherwise stated. Also, it should be understood that the terms used in this specification have the meanings commonly used in the relevant field unless otherwise specified. Thus, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present specification (including definitions) will control.

(definition)
First, the terms and general techniques used in this disclosure will be explained.

As used herein, unless otherwise specified, the term "group" means a monovalent group. Examples of non-univalent groups include alkylene groups (divalent) and the like. In addition, in the following description of substituents and the like, the term "group" may be omitted.

In the present specification, the number of substituents defined by "optionally substituted" or "substituted" is not particularly limited, and is not particularly limited as long as it can be substituted. or multiple. Also, unless otherwise indicated, the description of each substituent also applies when that substituent is part or a substituent of another substituent.

As used herein, "maximum possible number of substituents" means the maximum number of substituents that a group can have, and can be different for each group. For example, 3 for a methyl group, 5 for an ethyl group, 7 for a benzyl group, and 11 for a naphthalenylethyl group.

In groups modified herein with "optionally substituted" or "substituted", any portion of the group may be substituted. For example, “optionally substituted arylalkyl” and “substituted arylalkyl” refer to the aryl portion being substituted, the alkyl portion being substituted, and both the aryl and alkyl portions being may be substituted.

As used herein, substituents in the case of "optionally substituted" may be one or more of the same or different substituents selected from any of Substituent Groups I to VI below. The type of atoms in the substituent involved in the bond is not particularly limited depending on the type of the substituent, but when the atom to which the substituent is bonded is an oxygen atom, a nitrogen atom, or a sulfur atom, the bonding point in the substituent below is is limited to and selected from carbon atoms.

Substituent Group I includes halogen, hydroxy, oxo, carboxy, amino, imino, hydroxyamino, hydroxyimino, formyl, formyloxy, carbamoyl, sulfamoyl, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azide, hydrazino, ureido, amidino, guanidino, unsubstituted or substituted alkyl, unsubstituted or substituted alkenyl, unsubstituted or substituted alkynyl, unsubstituted or substituted aryl, unsubstituted or substituted cycloalkyl, unsubstituted or substituted heteroaryl, unsubstituted or substituted heterocycloalkyl, unsubstituted or substituted alkyloxy, unsubstituted or substituted alkenyloxy, unsubstituted or substituted alkynyloxy, unsubstituted or substituted aryl-L _X -oxy, unsubstituted or substituted cycloalkyl -L _X -oxy, unsubstituted or substituted heteroaryl-L _X -oxy, unsubstituted or substituted heterocycloalkyl-L _X -oxy, unsubstituted or substituted alkyloxyalkyl, unsubstituted or substituted alkenyloxyalkyl, unsubstituted or substituted alkynyloxyalkyl, unsubstituted or substituted aryloxyalkyl, unsubstituted or substituted cycloalkyloxyalkyl, unsubstituted or substituted heteroaryloxyalkyl, unsubstituted or substituted heterocycloalkyloxyalkyl, unsubstituted or substituted alkyloxyalkyloxy, unsubstituted or substituted alkenyloxyalkyloxy, unsubstituted or substituted alkynyloxyalkyloxy, unsubstituted or substituted aryloxyalkyloxy, unsubstituted or substituted cycloalkyloxyalkyloxy, unsubstituted or substituted heteroaryloxyalkyloxy, unsubstituted or substituted heterocycloalkyloxyalkyloxy, unsubstituted or substituted alkylcarbonyl, unsubstituted or substituted alkenylcarbonyl, unsubstituted or substituted alkynylcarbonyl, unsubstituted or substituted aryl-L _X -carbonyl, unsubstituted or substituted cycloalkyl-L _X - carbonyl, unsubstituted or substituted heteroaryl-L _X -carbonyl, unsubstituted or substituted heterocycloalkyl-L _X -carbonyl, unsubstituted or substituted alkylcarbonyloxy, unsubstituted or substituted alkenylcarbonyloxy, unsubstituted or substituted alkynylcarbonyloxy , unsubstituted or substituted aryl-L _X -carbonyloxy, unsubstituted or substituted cycloalkyl-L _X -carbonyloxy, unsubstituted or substituted heteroaryl-L _X -carbonyloxy, unsubstituted or substituted heterocycloalkyl-L _X - carbonyloxy, unsubstituted or substituted alkylcarbonylamino, unsubstituted or substituted alkenylcarbonylamino, unsubstituted or substituted alkynylcarbonylamino, unsubstituted or substituted aryl-L _X -carbonylamino, unsubstituted or substituted cycloalkyl-L _X -carbonyl amino, unsubstituted or substituted heteroaryl-L _X -carbonylamino, unsubstituted or substituted heterocycloalkyl-L _X -carbonylamino, unsubstituted or substituted alkylcarbonylthio, unsubstituted or substituted alkenylcarbonylthio, unsubstituted or substituted alkynyl carbonylthio, unsubstituted or substituted aryl-L _X -carbonylthio, unsubstituted or substituted cycloalkyl-L _X -carbonylthio, unsubstituted or substituted heteroaryl-L _X -carbonylthio, unsubstituted or substituted heterocycloalkyl-L _X -carbonylthio, unsubstituted or substituted alkylcarbonylimino, unsubstituted or substituted alkenylcarbonylimino, unsubstituted or substituted alkynylcarbonylimino, unsubstituted or substituted aryl-L _X -carbonylimino, unsubstituted or substituted cycloalkyl-L _X -carbonylimino, unsubstituted or substituted heteroaryl-L _X -carbonylimino, unsubstituted or substituted heterocycloalkyl-L _X -carbonylimino, unsubstituted or substituted alkylthio, unsubstituted or substituted alkenylthio, unsubstituted or substituted alkynylthio , unsubstituted or substituted aryl-L _X -thio, unsubstituted or substituted cycloalkyl-L _X -thio, unsubstituted or substituted heteroaryl-L _X -thio, unsubstituted or substituted heterocycloalkyl-L _X -thio, non substituted or substituted alkylamino, unsubstituted or substituted alkenylamino, unsubstituted or substituted alkynylamino, unsubstituted or substituted alkynylamino, unsubstituted or substituted aryl-L _X -amino, unsubstituted or substituted cycloalkyl-L _X -amino, unsubstituted or substituted heteroaryl-L _X -amino, unsubstituted or substituted heterocycloalkyl-L _X -amino, unsubstituted or substituted alkylsulfonyl, unsubstituted or substituted alkenylsulfonyl, unsubstituted or substituted alkynylsulfonyl, unsubstituted or substituted Aryl-L _X -sulfonyl, unsubstituted or substituted cycloalkyl-L _X -sulfonyl, unsubstituted or substituted heteroaryl-L _X -sulfonyl, unsubstituted or substituted heterocycloalkyl-L _X -sulfonyl, unsubstituted or substituted alkylsulfonyl amino, unsubstituted or substituted alkenylsulfonylamino, unsubstituted or substituted alkynylsulfonylamino, unsubstituted or substituted aryl-L _X -sulfonylamino, unsubstituted or substituted cycloalkyl-L _X -sulfonylamino, unsubstituted or substituted heteroaryl- L _X -sulfonylamino, unsubstituted or substituted heterocycloalkyl-L _X -sulfonylamino, unsubstituted or substituted alkylimino, unsubstituted or substituted alkenylimino, unsubstituted or substituted alkynylimino, unsubstituted or substituted aryl-L _X - imino, unsubstituted or substituted cycloalkyl-L _X -imino, unsubstituted or substituted heteroaryl-L _X -imino, unsubstituted or substituted heterocycloalkyl-L _X -imino, unsubstituted or substituted alkyloxyimino, unsubstituted or substituted alkenyloxyimino, unsubstituted or substituted alkynyloxyimino, unsubstituted or substituted aryl-L _X -oximino, unsubstituted or substituted cycloalkyl-L _X -oximino, unsubstituted or substituted heteroaryl-L _X -oximino, unsubstituted or substituted heterocycloalkyl-L _X -oxyimino, unsubstituted or substituted alkyloxycarbonyl, unsubstituted or substituted alkenyloxycarbonyl, unsubstituted or substituted alkynyloxycarbonyl, unsubstituted or substituted aryl-L _X -oxycarbonyl, unsubstituted or substituted cycloalkyl-L _X -oxycarbonyl, unsubstituted or substituted heteroaryl-L _X -oxycarbonyl, unsubstituted or substituted heterocycloalkyl-L _X -oxycarbonyl, unsubstituted or substituted alkyloxycarbonylamino, unsubstituted or substituted alkenyloxycarbonylamino, unsubstituted or substituted alkynyloxycarbonylamino, unsubstituted or substituted aryl-L _X -oxycarbonylamino, unsubstituted or substituted cycloalkyl-L _X -oxycarbonylamino, unsubstituted or substituted heteroaryl-L _X -oxycarbonylamino, unsubstituted or substituted heterocycloalkyl-L _X -oxycarbonylamino, unsubstituted or substituted alkylsulfanyl, unsubstituted or substituted alkenylsulfanyl, unsubstituted or substituted alkynylsulfanyl, unsubstituted or substituted aryl-L _X - sulfanyl, unsubstituted or substituted cycloalkyl-L _X -sulfanyl, unsubstituted or substituted heteroaryl-L _X -sulfanyl, unsubstituted or substituted heterocycloalkyl-L _X -sulfanyl, unsubstituted or substituted alkylsulfinyl, unsubstituted or substituted alkenylsulfinyl, unsubstituted or substituted alkynylsulfinyl, unsubstituted or substituted aryl-L _X -sulfinyl, unsubstituted or substituted cycloalkyl-L _X -sulfinyl, unsubstituted or substituted heteroaryl-L _X -sulfinyl, unsubstituted or substituted hetero Cycloalkyl-L _X -sulfinyl, unsubstituted or substituted alkylcarbamoyl, unsubstituted or substituted alkenylcarbamoyl, unsubstituted or substituted alkynylcarbamoyl, unsubstituted or substituted aryl-L _X -carbamoyl, unsubstituted or substituted cycloalkyl-L _X - Carbamoyl, unsubstituted or substituted heteroaryl-L _X -carbamoyl, unsubstituted or substituted heterocycloalkyl-L _X -carbamoyl, unsubstituted or substituted alkylsulfamoyl, unsubstituted or substituted alkenylsulfamoyl, unsubstituted or substituted alkynyl sulfamoyl, unsubstituted or substituted aryl-L _X -sulfamoyl, unsubstituted or substituted cycloalkyl-L _X -sulfamoyl, unsubstituted or substituted heteroaryl-L _X -sulfamoyl, and unsubstituted or substituted heterocycloalkyl-L _X -sulfamoyl, wherein L _X is a single bond or unsubstituted or substituted alkylene;
Substituted alkyl, substituted alkenyl, substituted alkynyl, substituted aryl, substituted cycloalkyl, substituted heteroaryl, substituted heterocycloalkyl, and substituted alkylene moieties (in whole or in part) in the substituent groups are each independently halogen , hydroxy, oxo, carboxy, amino, imino, hydroxyamino, hydroxyimino, formyl, formyloxy, carbamoyl, sulfamoyl, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azide , hydrazino, ureido, amidino, guanidino, alkyl, alkenyl, alkynyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, alkyloxy, alkenyloxy, alkynyloxy, aryl-L _X -oxy, cycloalkyl-L _X -oxy , heteroaryl-L _X -oxy, heterocycloalkyl-L _X -oxy, alkyloxyalkyl, alkenyloxyalkyl, alkynyloxyalkyl, aryloxyalkyl, cycloalkyloxyalkyl, heteroaryloxyalkyl, heterocycloalkyloxyalkyl, alkyloxyalkyloxy, alkenyloxyalkyloxy, alkynyloxyalkyloxy, aryloxyalkyloxy, cycloalkyloxyalkyloxy, heteroaryloxyalkyloxy, heterocycloalkyloxyalkyloxy, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, aryl- L _X -carbonyl, cycloalkyl-L _X -carbonyl, heteroaryl-L X -carbonyl, heterocycloalkyl-L _X -carbonyl, alkylcarbonyloxy, alkenylcarbonyloxy _, alkynylcarbonyloxy, aryl-L _X -carbonyloxy, Cycloalkyl-L _X -carbonyloxy, heteroaryl-L _X -carbonyloxy, heterocycloalkyl-L _X -carbonyloxy, alkylcarbonylamino, alkenylcarbonylamino, alkynylcarbonylamino, aryl-L _X -carbonylamino, cycloalkyl -L _X -carbonylamino, heteroaryl-L X -carbonylamino, heterocycloalkyl-L _X -carbonylamino, alkylcarbonylthio, alkenylcarbonylthio, alkynylcarbonylthio, aryl-L _X -carbonylthio, cycloalkyl- _{L X} -carbonylthio, heteroaryl-L X -carbonylthio, heterocycloalkyl-L _X -carbonylthio, alkylcarbonylimino, alkenylcarbonylimino, alkynylcarbonylimino, aryl- _{L X} -carbonylimino, cycloalkyl-L _X - carbonylimino, heteroaryl-L _X -carbonylimino, heterocycloalkyl-L X _{-carbonylimino} , alkylthio, alkenylthio, alkynylthio, aryl-L _X -thio, cycloalkyl-L _X -thio, heteroaryl-L _X -thio, heterocycloalkyl-L _X -thio, alkylamino, alkenylamino, alkynylamino, alkynylamino, aryl-L _X -amino, cycloalkyl-L _X -amino, heteroaryl-L _X -amino, heterocycloalkyl -L _X -amino, alkylsulfonyl, _{alkenylsulfonyl} , alkynylsulfonyl, aryl-L _X -sulfonyl, cycloalkyl-L X -sulfonyl, heteroaryl-L _X -sulfonyl, heterocycloalkyl-L _X -sulfonyl, alkylsulfonylamino , alkenylsulfonylamino, alkynylsulfonylamino, aryl-L _X -sulfonylamino, cycloalkyl-L X -sulfonylamino, heteroaryl- _{L X} -sulfonylamino, heterocycloalkyl-L _X -sulfonylamino, alkylimino, alkenylimino , alkynylimino, aryl-L _X -imino, cycloalkyl-L X -imino, heteroaryl-L _X -imino, heterocycloalkyl-L _X -imino, alkyloxyimino, alkenyloxyimino _, alkynyloxyimino, aryl- L _X -oximino, cycloalkyl-L _{X -oximino} , heteroaryl-L X -oximino, heterocycloalkyl-L _X -oximino, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, aryl-L _X -oxycarbonyl, Cycloalkyl-L _X -oxycarbonyl, heteroaryl-L X -oxycarbonyl, heterocycloalkyl- _{L X} -oxycarbonyl, alkyloxycarbonylamino, alkenyloxycarbonylamino, alkynyloxycarbonylamino, aryl-L _X -oxycarbonyl amino, cycloalkyl-L _X -oxycarbonylamino, heteroaryl-L _X -oxycarbonylamino, heterocycloalkyl-L X -oxycarbonylamino, alkylsulfanyl, alkenylsulfanyl, _{alkynylsulfanyl} , aryl-L _X -sulfanyl, cyclo Alkyl-L _X -sulfanyl, heteroaryl-L X -sulfanyl, heterocycloalkyl-L _X -sulfanyl, alkylsulfinyl, alkenylsulfinyl, alkynylsulfinyl, aryl- _{L X -sulfinyl} , cycloalkyl-L _X -sulfinyl, heteroaryl -L _X -sulfinyl, heterocycloalkyl-L _X -sulfinyl, alkylcarbamoyl, alkenylcarbamoyl, alkynylcarbamoyl, aryl-L _X -carbamoyl, cycloalkyl-L _X -carbamoyl, heteroaryl-L _X -carbamoyl, heterocycloalkyl -L _X -carbamoyl, alkylsulfamoyl, alkenylsulfamoyl, alkynylsulfamoyl, aryl-L X -sulfamoyl, cycloalkyl _{-L X -sulfamoyl} , heteroaryl-L _X -sulfamoyl, and heterocycloalkyl-L It has from 1 to the maximum possible number of substituents which are the same or different and are selected from the group consisting of _X -sulfamoyl.

Substituent Group II includes halogen, hydroxy, oxo, carboxy, amino, imino, hydroxyamino, hydroxyimino, formyl, formyloxy, carbamoyl, sulfamoyl, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azide, hydrazino, ureido, amidino, guanidino, unsubstituted or substituted C _1-12 alkyl, unsubstituted or substituted C _2-12 alkenyl, unsubstituted or substituted C _2-12 alkynyl, unsubstituted or substituted C _6-10 aryl, unsubstituted or substituted C _3-10 cycloalkyl, unsubstituted or substituted 5-10 membered heteroaryl, unsubstituted or substituted 5-10 membered heterocycloalkyl, unsubstituted or substituted C _1-12 alkyloxy , unsubstituted or substituted C _2-12 alkenyloxy, unsubstituted or substituted C _2-12 alkynyloxy, unsubstituted or substituted C _6-10 aryl-L _X -oxy, unsubstituted or substituted C _3-10 cycloalkyl-L _X -oxy, unsubstituted or substituted 5-10 membered heteroaryl-L _X -oxy, unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -oxy, unsubstituted or substituted C _1-12 alkyloxyC _{1- 12} alkyl, unsubstituted or substituted C _2-12 alkenyloxy C _1-12 alkyl, unsubstituted or substituted C _2-12 alkynyloxy C _1-12 alkyl, unsubstituted or substituted C _6-10 aryloxy C _1-12 alkyl , unsubstituted or substituted C _3-10 cycloalkyloxy C _1-12 alkyl, unsubstituted or substituted 5-10 membered heteroaryloxy C _1-12 alkyl, unsubstituted or substituted 5-10 membered heterocycloalkyloxy C _{1- 12} alkyl, unsubstituted or substituted C _1-12 alkyloxyC _1-12 alkyloxy, unsubstituted or substituted C _2-12 alkenyloxyC _1-12 alkyloxy, unsubstituted or substituted C _2-12 alkynyloxyC _{1- 12} alkyloxy, unsubstituted or substituted C _6-10 aryloxy C _1-12 alkyloxy, unsubstituted or substituted C _3-10 cycloalkyloxy C _1-12 alkyloxy, unsubstituted or substituted 5- to 10-membered heteroaryloxy C _1-12 alkyloxy, unsubstituted or substituted 5-10 membered heterocycloalkyloxy C _1-12 alkyloxy, unsubstituted or substituted C _1-12 alkylcarbonyl, unsubstituted or substituted C _2-12 alkenylcarbonyl, unsubstituted or substituted C _2-12 alkynylcarbonyl, unsubstituted or substituted C _6-10 aryl-L _X -carbonyl, unsubstituted or substituted C _3-10 cycloalkyl-L _X -carbonyl, unsubstituted or substituted 5-10 membered heteroaryl -L _X -carbonyl, unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -carbonyl, unsubstituted or substituted C _1-12 alkylcarbonyloxy, unsubstituted or substituted C _2-12 alkenylcarbonyloxy, unsubstituted or substituted C _2-12 alkynylcarbonyloxy, unsubstituted or substituted C _6-10 aryl-L _X -carbonyloxy, unsubstituted or substituted C _3-10 cycloalkyl-L _X -carbonyloxy, unsubstituted or substituted 5-10 membered heteroaryl-L _X -carbonyloxy, unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -carbonyloxy, unsubstituted or substituted C _1-12 alkylcarbonylamino, unsubstituted or substituted C _2-12 alkenylcarbonylamino , unsubstituted or substituted C _2-12 alkynylcarbonylamino, unsubstituted or substituted C _6-10 aryl-L _X -carbonylamino, unsubstituted or substituted C _3-10 cycloalkyl-L _X -carbonylamino, unsubstituted or substituted 5-10 membered heteroaryl-L _X -carbonylamino, unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -carbonylamino, unsubstituted or substituted C _1-12 alkylcarbonylthio, unsubstituted or substituted C _{2- 12} alkenylcarbonylthio, unsubstituted or substituted C _2-12 alkynylcarbonylthio, unsubstituted or substituted C _6-10 aryl-L _X -carbonylthio, unsubstituted or substituted C _3-10 cycloalkyl-L _X -carbonylthio, unsubstituted or substituted 5-10 membered heteroaryl-L _X -carbonylthio, unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -carbonylthio, unsubstituted or substituted C _1-12 alkylcarbonylimino, unsubstituted or substituted C _2-12 alkenylcarbonylimino, unsubstituted or substituted C _2-12 alkynylcarbonylimino, unsubstituted or substituted C _6-10 aryl-L _X -carbonylimino, unsubstituted or substituted C _3-10 cycloalkyl-L _X -carbonylimino, unsubstituted or substituted 5- to 10-membered heteroaryl-L _X -carbonylimino, unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -carbonylimino, unsubstituted or substituted C _1-12 alkylthio, unsubstituted substituted or substituted C _2-12 alkenylthio, unsubstituted or substituted C _2-12 alkynylthio, unsubstituted or substituted C _6-10 aryl-L _X -thio, unsubstituted or substituted C _3-10 cycloalkyl-L _X - thio, unsubstituted or substituted 5- to 10-membered heteroaryl-L _X -thio,
unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -thio, unsubstituted or substituted C _1-12 alkylamino, unsubstituted or substituted C _2-12 alkenylamino, unsubstituted or substituted C _2-12 alkynylamino, unsubstituted or substituted C _2-12 alkynylamino, unsubstituted or substituted C _6-10 aryl-L _X -amino, unsubstituted or substituted C _3-10 cycloalkyl-L _X -amino, unsubstituted or substituted 5-10 membered heteroaryl-L _X -amino, unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -amino, unsubstituted or substituted C _1-12 alkylsulfonyl, unsubstituted or substituted C _2-12 alkenylsulfonyl, unsubstituted or substituted C _2-12 alkynylsulfonyl, unsubstituted or substituted C _6-10 aryl-L _X -sulfonyl, unsubstituted or substituted C _3-10 cycloalkyl-L _X -sulfonyl, unsubstituted or substituted 5-10 membered heteroaryl- L _X -sulfonyl, unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -sulfonyl, unsubstituted or substituted C _1-12 alkylsulfonylamino, unsubstituted or substituted C _2-12 alkenylsulfonylamino, unsubstituted or substituted C _2-12 alkynylsulfonylamino, unsubstituted or substituted C _6-10 aryl-L _X -sulfonylamino, unsubstituted or substituted C _3-10 cycloalkyl-L _X -sulfonylamino, unsubstituted or substituted 5-10 membered hetero Aryl-L _X -sulfonylamino, unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -sulfonylamino, unsubstituted or substituted C _1-12 alkylimino, unsubstituted or substituted C _2-12 alkenylimino, unsubstituted or substituted C _2-12 alkynylimino, unsubstituted or substituted C _6-10 aryl-L _X -imino, unsubstituted or substituted C _3-10 cycloalkyl-L _X -imino, unsubstituted or substituted 5-10 membered heteroaryl -L _X -imino, unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -imino, unsubstituted or substituted C _1-12 alkyloxyimino, unsubstituted or substituted C _2-12 alkenyloxyimino, unsubstituted or substituted C _2-12 alkynyloxyimino, unsubstituted or substituted C _6-10 aryl-L _X -oximino, unsubstituted or substituted C _3-10 cycloalkyl-L _X -oximino, unsubstituted or substituted 5-10 membered heteroaryl -L _X -oximino, unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -oximino, unsubstituted or substituted C _1-12 alkyloxycarbonyl, unsubstituted or substituted C _2-12 alkenyloxycarbonyl, unsubstituted or substituted C _2-12 alkynyloxycarbonyl, unsubstituted or substituted C _6-10 aryl-L _X -oxycarbonyl, unsubstituted or substituted C _3-10 cycloalkyl-L _X -oxycarbonyl, unsubstituted or substituted 5-10 membered heteroaryl-L _X -oxycarbonyl, unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -oxycarbonyl, unsubstituted or substituted C _1-12 alkyloxycarbonylamino, unsubstituted or substituted C _2-12 alkenyloxy carbonylamino, unsubstituted or substituted C _2-12 alkynyloxycarbonylamino, unsubstituted or substituted C _6-10 aryl-L _X -oxycarbonylamino, unsubstituted or substituted C _3-10 cycloalkyl-L _X -oxycarbonylamino , unsubstituted or substituted 5- to 10-membered heteroaryl-L _X -oxycarbonylamino, unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -oxycarbonylamino, unsubstituted or substituted C _1-12 alkylsulfanyl, non substituted or substituted C _2-12 alkenylsulfanyl, unsubstituted or substituted C _2-12 alkynylsulfanyl, unsubstituted or substituted C _6-10 aryl-L _X -sulfanyl, unsubstituted or substituted C _3-10 cycloalkyl-L _X - sulfanyl, unsubstituted or substituted 5-10 membered heteroaryl-L _X -sulfanyl, unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -sulfanyl, unsubstituted or substituted C _1-12 alkylsulfinyl, unsubstituted or substituted C _2-12 alkenylsulfinyl, unsubstituted or substituted C _2-12 alkynylsulfinyl, unsubstituted or substituted C _6-10 aryl-L _X -sulfinyl, unsubstituted or substituted C _3-10 cycloalkyl-L _X -sulfinyl, unsubstituted substituted or substituted 5-10 membered heteroaryl-L _X -sulfinyl, unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -sulfinyl, unsubstituted or substituted C _1-12 alkylcarbamoyl, unsubstituted or substituted C _{2- 12} alkenylcarbamoyl, unsubstituted or substituted C _2-12 alkynylcarbamoyl, unsubstituted or substituted C _6-10 aryl-L _X -carbamoyl, unsubstituted or substituted C _3-10 cycloalkyl-L _X -carbamoyl, unsubstituted or substituted 5-10 membered heteroaryl-L _X -carbamoyl, unsubstituted or substituted 5-10 membered heterocycloalkyl-L _X -carbamoyl, unsubstituted or substituted C _1-12 alkylsulfamoyl, unsubstituted or substituted C _2-12 alkenylsulfamoyl, unsubstituted or substituted C _2-12 alkynylsulfamoyl, unsubstituted or substituted C _6-10 aryl-L _X -sulfamoyl, unsubstituted or substituted C _3-10 cycloalkyl-L _X -sulfamoyl, unsubstituted substituted or substituted 5- to 10-membered heteroaryl-L _X -sulfamoyl, and unsubstituted or substituted 5- to 10-membered heterocycloalkyl-L _X -sulfamoyl, wherein L _X is a single bond or an unsubstituted or substituted C _1-12 alkylene,
Substituted C _1-12 alkyl, substituted C _2-12 alkenyl, substituted C _2-12 alkynyl, substituted C _6-10 aryl, substituted C _3-10 cycloalkyl, substituted 5- to 10-membered heteroaryl in the substituent group , substituted 5- to 10-membered heterocycloalkyl, and substituted alkylene moieties (in whole or in part) are each independently halogen, hydroxy, oxo, carboxy, amino, imino, hydroxyamino, hydroxyimino, formyl, formyloxy, carbamoyl, sulfamoyl, sulfanyl, sulfino, sulfo, thioformyl, thiocarboxy, dithiocarboxy, thiocarbamoyl, cyano, nitro, nitroso, azide, hydrazino, ureido, amidino, guanidino, C _1-12 alkyl, C _1-12 haloalkyl, C _2-12 alkenyl, C _2-12 alkynyl, C _6-10 aryl, C _3-10 cycloalkyl, 5-10 membered heteroaryl, 5-10 membered heterocycloalkyl, C _1-12 alkyloxy, C _1-12 haloalkyloxy, C _2-12 alkenyloxy, C _2-12 alkynyloxy, C _6-10 aryl- _{L X} -oxy, C _3-10 cycloalkyl-L _X -oxy, 5- to 10-membered heteroaryl-L _X - oxy, 5- to 10-membered heterocycloalkyl-L _X -oxy, C _1-12 alkyloxyalkyl, C _2-12 alkenyloxyalkyl, C _2-12 alkynyloxyalkyl, C _6-10 aryloxyalkyl, C _{3- 10} cycloalkyloxyalkyl, 5-10 membered heteroaryloxyalkyl, 5-10 membered heterocycloalkyloxyalkyl, C _1-12 alkyloxyalkyloxy, C _2-12 alkenyloxyalkyloxy, C _2-12 alkynyloxyalkyl oxy, C _6-10 aryloxyalkyloxy, C _3-10 cycloalkyloxyalkyloxy, 5-10 membered heteroaryloxyalkyloxy, 5-10 membered heterocycloalkyloxyalkyloxy, C _1-12 alkylcarbonyl, C _2-12 alkenylcarbonyl, C _2-12 alkynylcarbonyl, C _6-10 aryl-L _X -carbonyl, C _3-10 cycloalkyl-L _X -carbonyl, 5- to 10-membered heteroaryl-L _X -carbonyl, 5- 10-membered heterocycloalkyl-L _X -carbonyl, C _1-12 alkylcarbonyloxy, C 2-12 alkenylcarbonyloxy, _{C 2-12 alkynylcarbonyloxy} , C _6-10 aryl-L _X -carbonyloxy, C _{3- 10} cycloalkyl-L _X -carbonyloxy, 5-10 membered heteroaryl-L _X -carbonyloxy, 5-10 membered heterocycloalkyl-L _X -carbonyloxy, C _1-12 alkylcarbonylamino, C _2-12 alkenyl carbonylamino, C _2-12 alkynylcarbonylamino, C _6-10 aryl-L _X -carbonylamino, C _3-10 cycloalkyl-L _X -carbonylamino, 5-10 membered heteroaryl-L _X -carbonylamino, 5 ~10 membered heterocycloalkyl-L _X -carbonylamino, C _1-12 alkylcarbonylthio, C _2-12 alkenylcarbonylthio, C _2-12 alkynylcarbonylthio, C _6-10 aryl-L _X -carbonylthio, C _3-10 cycloalkyl-L _X -carbonylthio, 5-10 membered heteroaryl-L _X -carbonylthio, 5-10 membered heterocycloalkyl-L _X -carbonylthio, C _1-12 alkylcarbonylimino, C _{2- 12} alkenylcarbonylimino, C _2-12 alkynylcarbonylimino, C _6-10 aryl-L _X -carbonylimino, C _3-10 cycloalkyl-L _X -carbonylimino, 5- to 10-membered heteroaryl- _{L X} -carbonylimino , 5-10 membered heterocycloalkyl-L _X -carbonylimino, C _1-12 alkylthio, C _2-12 alkenylthio, C _2-12 alkynylthio, C _6-10 aryl-L _X -thio, C _3-10 Cycloalkyl-L _X -thio, 5-10 membered heteroaryl-L _X -thio, 5-10 membered heterocycloalkyl-L _X -thio, C _1-12 alkylamino, C _2-12 alkenylamino, C _{2- 12} alkynylamino, C _2-12 alkynylamino, C _6-10 aryl- _{L X} -amino, C _3-10 cycloalkyl-L _X -amino, 5-10 membered heteroaryl-L _X -amino, 5-10 membered heterocycloalkyl-L _X -amino, C _1-12 alkylsulfonyl, C _2-12 alkenylsulfonyl, C _2-12 alkynylsulfonyl, C _6-10 aryl-L _X -sulfonyl, C _3-10 cycloalkyl-L _X -sulfonyl, 5-10 membered heteroaryl-L _X -sulfonyl, 5-10 membered heterocycloalkyl-L _X -sulfonyl, C _1-12 alkylsulfonylamino, C _2-12 alkenylsulfonylamino, C _2-12 alkynylsulfonyl amino, C _6-10 aryl-L _X -sulfonylamino, C _3-10 cycloalkyl-L _X -sulfonylamino, 5-10 membered heteroaryl-L _X -sulfonylamino, 5-10 membered heterocycloalkyl-L _X -sulfonylamino, C _1-12 alkylimino, C _2-12 alkenylimino, C _2-12 alkynylimino, C _6-10 aryl-L _X -imino, C _3-10 cycloalkyl-L _X -imino, 5- 10-membered heteroaryl-L _X -imino, 5- to 10-membered heterocycloalkyl- _{L X} -imino, C _1-12 alkyloxyimino, C _2-12 alkenyloxyimino, C _2-12 alkynyloxyimino, C _{6- 10} aryl-L _X -oximino, C _3-10 cycloalkyl-L _X -oximino _, 5-10 membered heteroaryl-L X -oximino, 5-10 membered heterocycloalkyl-L _X -oximino, C _1-12 alkyl oxycarbonyl, C _2-12 alkenyloxycarbonyl, C _2-12 alkynyloxycarbonyl, C _6-10 aryl-L _X -oxycarbonyl, C _3-10 cycloalkyl- _L X -oxycarbonyl, 5-10 membered heteroaryl -L _X -oxycarbonyl, 5-10 membered heterocycloalkyl-L _X -oxycarbonyl, C _1-12 alkyloxycarbonylamino, C _2-12 alkenyloxycarbonylamino, C _2-12 alkynyloxycarbonylamino, C _{6 -10} aryl-L _X -oxycarbonylamino, C _3-10 cycloalkyl-L _X -oxycarbonylamino, 5-10 membered heteroaryl-L _X -oxycarbonylamino, 5-10 membered heterocycloalkyl-L _X - oxycarbonylamino, C _1-12 alkylsulfanyl, C 2-12 alkenylsulfanyl _, C _2-12 alkynylsulfanyl, C _6-10 aryl-L _X -sulfanyl, C _3-10 cycloalkyl-L _X -sulfanyl, 5- 10-membered heteroaryl-L _X -sulfanyl, 5- to 10-membered heterocycloalkyl-L _X -sulfanyl, C _1-12 alkylsulfinyl, C _2-12 alkenylsulfinyl, C _2-12 alkynylsulfinyl, C _6-10 aryl- L _X -sulfinyl, C _3-10 cycloalkyl-L _X -sulfinyl, 5-10 membered heteroaryl-L _X -sulfinyl, 5-10 membered heterocycloalkyl-L _X -sulfinyl, C _1-12 alkylcarbamoyl, C _2-12 alkenylcarbamoyl, C _2-12 alkynylcarbamoyl, C _6-10 aryl-L _X -carbamoyl, C _3-10 cycloalkyl-L _X -carbamoyl, 5- to 10-membered heteroaryl-L _X -carbamoyl, 5- 10-membered heterocycloalkyl-L _X -carbamoyl, C _1-12 alkylsulfamoyl, C _2-12 alkenylsulfamoyl, C _2-12 alkynylsulfamoyl, C _6-10 aryl-L _X -sulfamoyl, C 1 to the maximum substitutable number selected from the group consisting of _3-10 cycloalkyl-L _X -sulfamoyl, 5- to 10-membered heteroaryl-L _X -sulfamoyl, and 5- to 10-membered heterocycloalkyl-L _X -sulfamoyl; having the same or different substituents up to .

Substituent Group III is halogen, hydroxy, carboxy, amino, carbamoyl, nitro, guanidino, alkyl, aryl, cycloalkyl, heteroaryl, alkyloxy, alkylcarbonyl, cycloalkylcarbonyl, alkylcarbonylamino, cycloalkylcarbonylamino, alkyl consisting of amino, cycloalkylalkylamino, alkyloxycarbonyl, and trialkylsilyloxy, wherein said groups of substituent groups are halogen, hydroxy, carboxy, amino, carbamoyl, nitro, alkyl, haloalkyl, aryl, haloaryl, alkyl It may be substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of oxy, haloalkyloxy and alkyloxycarbonyl.
Substituent group III is preferably substituent group III', which is halogen, hydroxy, carboxy, amino, carbamoyl, nitro, guanidino, C _1-12 alkyl, C _6-10 aryl, C _3-10 cyclo alkyl, 5-10 membered heteroaryl, C _1-12 alkyloxy, C _1-12 alkylcarbonyl, C _3-10 cycloalkylcarbonyl, C _1-12 alkylcarbonylamino, C _3-10 cycloalkylcarbonylamino, C _{1 -12} alkylamino, C _3-10 cycloalkylC _1-6 alkylamino, C _1-12 alkyloxycarbonyl, and triC _1-6 alkylsilyloxy, wherein these groups in said substituent group are halogen , hydroxy, carboxy, amino, carbamoyl, nitro, C _1-12 alkyl, C _1-12 haloalkyl, C _6-10 aryl, C _6-10 haloaryl, C _1-12 alkyloxy, C _1-12 haloalkyloxy, and It may be substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of C _1-12 alkyloxycarbonyl.

Substituent Group IV includes halogen, hydroxy, carboxy, amino, carbamoyl, nitro, amidino, alkyl, aryl, cycloalkyl, heteroarylheterocycloalkyl, arylalkyl, cycloalkylalkyl, alkyloxy, aryloxy, alkylcarbonyl, cyclo Alkylcarbonyl, alkyloxycarbonyl, and trialkylsilyloxy, wherein these groups of said substituent groups are halogen, hydroxy, carboxy, amino, carbamoyl, nitro, alkyl, haloalkyl, alkyloxy, haloalkyloxy, and alkyloxy. It may be substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of carbonyl.
Substituent group IV is preferably substituent group IV', which is halogen, hydroxy, carboxy, amino, carbamoyl, nitro, amidino, C _1-6 alkyl, C _6-10 aryl, C _3-10 cyclo Alkyl, 5-10 membered heteroaryl 5-10 membered heterocycloalkyl, C _6-10 arylC _1-6 alkyl, C _3-10 cycloalkylC _1-6 alkyl, C _1-6 alkyloxy, C _6-10 aryloxy, C _1-6 alkylcarbonyl, C _3-10 cycloalkylcarbonyl, C _1-6 alkyloxycarbonyl, and tri-C _1-6 alkylsilyloxy, each of these groups independently consisting of halogen, hydroxy, carboxy, amino, carbamoyl, nitro, C _1-6 alkyl, C _1-6 haloalkyl, C _1-6 alkyloxy, C _1-6 haloalkyloxy, and C _1-6 alkyloxycarbonyl It may be substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group.

Substituent group V is halogen, hydroxy, carboxy, amino, formyl, carbamoyl, cyano, nitro, amidino, guanidino, alkyl, aryl, cycloalkyl, heteroaryl, heterocycloalkyl, alkyloxy, aryloxy, cycloalkyloxy, heteroaryloxy, heterocycloalkyloxy, alkyloxyoxy, alkylamino, arylamino, cycloalkylamino, heteroarylamino, heterocycloalkylamino, formyl, alkylcarbonyl, arylcarbonyl, cycloalkylcarbonyl, heteroarylcarbonyl, heterocyclo alkylcarbonyl, alkyloxycarbonyl, aryloxycarbonyl, cycloalkyloxycarbonyl, heteroaryloxycarbonyl, heterocycloalkyloxycarbonyl, alkylcarbamoyl, arylcarbamoyl, cycloalkylcarbamoyl, heteroarylcarbamoyl, and heterocycloalkylcarbamoyl, wherein and each of these groups in the above substituent groups is independently halogen, hydroxy, carboxy, amino, formyl, carbamoyl, cyano, nitro, amidino, guanidino, alkyl, alkyloxy, haloalkyl, haloalkyloxy, alkylamino, formyl , alkylcarbonyl, alkyloxycarbonyl, and alkylcarbamoyl, and may be substituted with the same or different substituents from one to the maximum substitutable number.
Substituent group V is preferably substituent group V′, which is halogen, hydroxy, carboxy, amino, formyl, carbamoyl, cyano, nitro, amidino, guanidino, C _1-12 alkyl, C _6-10 aryl , C _3-10 cycloalkyl, 5-10 membered heteroaryl, 5-10 membered heterocycloalkyl, C _1-12 alkyloxy, C _6-10 aryloxy, C _3-10 cycloalkyloxy, 5-10 membered hetero aryloxy, 5-10 membered heterocycloalkyloxy, C _1-12 alkylamino, C _6-10 arylamino, C _3-10 cycloalkylamino, 5-10 membered heteroarylamino, 5-10 membered heterocycloalkylamino , formyl, C _1-12 alkylcarbonyl, C _6-10 arylcarbonyl, C _3-10 cycloalkylcarbonyl, 5-10 membered heteroarylcarbonyl, 5-10 membered heterocycloalkylcarbonyl, C _1-12 alkyloxycarbonyl, C _6-10 aryloxycarbonyl, C _3-10 cycloalkyloxycarbonyl, 5-10 membered heteroaryloxycarbonyl, 5-10 membered heterocycloalkyloxycarbonyl, C _1-12 alkylcarbamoyl, C _6-10 arylcarbamoyl, consisting of C _3-10 cycloalkylcarbamoyl, 5- to 10-membered heteroarylcarbamoyl, and 5- to 10-membered heterocycloalkylcarbamoyl, wherein each of these groups in said substituent groups is independently halogen, hydroxy, carboxy , amino, formyl, carbamoyl, cyano, nitro, amidino, guanidino, C _1-6 alkyl, C _1-6 alkyloxy, C _1-6 haloalkyl, C _1-6 haloalkyloxy, C _1-6 alkylamino, formyl, optionally substituted with the same or different substituents selected from the group consisting of C _1-6 alkylcarbonyl, C _1-6 alkyloxycarbonyl and C _1-6 alkylcarbamoyl from 1 to the maximum number of possible substitutions; .

Substituent Group VI includes halogen, hydroxy, carboxy, amino, formyl, carbamoyl, cyano, nitro, amidino, guanidino, alkyl, alkyloxy, haloalkyl, haloalkyloxy, alkylamino, formyl, alkylcarbonyl, alkyloxycarbonyl, and alkyl Consists of carbamoyl.
Substituent group VI is preferably substituent group VI', which is halogen, hydroxy, carboxy, amino, formyl, carbamoyl, cyano, nitro, amidino, guanidino, C _1-6 alkyl, C _1-6 alkyl oxy, C _1-6 haloalkyl, C _1-6 haloalkyloxy, C _1-6 alkylamino, formyl, C _1-6 alkylcarbonyl, C _1-6 alkyloxycarbonyl, and C _1-6 alkylcarbamoyl.

Examples of substituents in the present specification that are "optionally substituted" include substituent group α and substituent group β. The substituent group α may be the substituent group α1, the substituent group α2 or the substituent group α3, and the substituent group β may be the substituent group β1, the substituent group β2 or the substituent group β3. The substituents in the case of "optionally substituted" may be selected from the substituent group α1, and may be substituted with 1 to 5 identical or different substituents. The type of atoms in the substituent involved in the bond is not particularly limited depending on the type of the substituent, but if the atom to which the substituent is bonded is an oxygen atom, a nitrogen atom, or a sulfur atom, the following substituents may be bonded. is limited to carbon atoms.
Substituent group α1 is
1) halogen atom 2) hydroxyl group 3) carboxyl group 4) cyano group 5) C _1-6 alkyl 6) C _2-6 alkenyl 7) C _2-6 alkynyl 8) C _1-6 alkoxy 9) C _1-6 alkylthio 10) C _1-6 alkylcarbonyl 11) C _1-6 alkylsulfonyl 12) 3- to 10-membered non-aryl heterocyclic carbonyl (with the proviso that 5) to 12) each substituent is selected from substituent group β1 , optionally substituted with 1 to 5 substituents that are the same or different)
13) C _3-10 alicyclic group 14) C _3-10 alicyclic oxy 15) C _6-10 aryloxy 16) 5- or 6-membered heteroaryloxy 17) 4-10 membered non-arylheterocyclic oxy 18) C _3-10 alicyclic thio 19) C _6-10 arylthio 20) 5- or 6-membered heteroarylthio 21) 4-10 membered non-aryl heterocyclic thio 22) C _6-10 aryl 23) C _{5 -10} heteroaryl24) 4-10 membered non-arylheterocycle25) _C3-10 alicyclic carbonyl26) _C6-10 arylcarbonyl27) 5- or 6-membered heteroarylcarbonyl28) 4-10 membered from non-arylheterocyclecarbonyl 29) C _3-10 alicyclicsulfonyl 30) C _6-10 arylsulfonyl 31) 5- or 6-membered heteroarylsulfonyl 32) 4- to 10-membered non-arylheterocyclesulfonyl (with the proviso that 13) Each substituent of 32) may be substituted by 1 to 5 substituent group β1 or the above 5) C _1-6 alkyl)
33)-NR ^10a R ^11a
34) —SO ₂ —NR ^10b R ^11b
35) —NR ^10c —C(=O)R ^11c
36) -NR ^10d -C(=O) OR ^11d
37) —NR ^12a —C(=O)NR ^10e R ^11e
38) —NR ¹⁰ⁱ —SO ₂ —R ¹¹ⁱ
39) —NR ^12c —SO ₂ —NR ^10j R ^11j
40) -C (=O) OR ^10k
41) -C(=O)NR ^10l R ^11k
42) -C(=O)NR ^10m OR ^11l
43) —C(=O)NR ^12d —NR ¹⁰ⁿ R ^11m
44) -C (=NR ^13a )R ^10s
45) -C (=NR ^13c ) NR ^10t R ^11q
46) -C (=NR ^13d ) NR ^12f -NR ^10u R ^11r
47) -NR ^17c -C (=NR ^13k )R ^17d
48) -NR ^12g -C (=NR ^13e ) -NR ^10v R ^11s
49) -NR ¹⁴ -C (=NR ^13f ) -NR ^12h -NR ^10w R ^11t
50) -OC(=O)R ^10x
51) -OC(=O) OR ^10y
52) —OC(=O)NR ^10z1 R ^11u
53) -NR ¹²ⁱ -NR ^10z2 R ^11v
54)-NR ^10z3 OR ^11w
55) protecting groups include
Substituent group β1 is
1) a halogen atom,
2) a hydroxyl group,
3) a carboxyl group,
4) a cyano group,
5) C _1-6 alkyl 6) C _3-10 alicyclic group,
7) C _1-6 alkoxy,
8) C _3-10 alicyclic oxy,
9) C _1-6 alkylthio,
10) 5- or 6-membered heteroarylthio,
11) C _6-10 aryl,
12) C _6-10 heteroaryl,
13) 3-10 membered non-aryl heterocycle,
14) C _1-6 alkylcarbonyl,
15) C _3-10 cycloaliphatic carbonyl,
16) C _6-10 arylcarbonyl,
17) 5- or 6-membered heteroarylcarbonyl,
18) 4-10 membered non-arylheterocyclic carbonyl,
19) —NR ^15a R ^16a ,
20) —SO ₂ —NR ^15b R ^16b ,
21) —NR ^15c —C(=O)R ^16c
22) —NR ^17a —C(=O)NR ^15d R ^16d ,
23) —C(=O)NR ^15e R ^16e ,
24) -C (=NR ^13g )R ^15f ,
25) -C (=NR ^13h ) NR ^15g R ^16f
26) —NR ^16g —C(=NR ¹³ⁱ )R ^15h
27) —NR ^17b —C (=NR ^13j ) —NR ¹⁵ⁱ R ^16h
28) -C (=O) OR ^10k
29) Each substituent of the protecting group (5) to 18) of the substituent group β1 is a halogen atom, hydroxyl group, cyano group, carboxyl group, C _1-6 alkoxy, C _6-10 aryl, —NR ^18a R optionally substituted with 1 to 5 substituents selected from the group consisting of ^18b ),
R ^13a , R ^13a2 , R ^13c , R ^13c2 , R ^13d , R ^13d2 , R ^13e , R ^13f , R ^13g , R ^13g2 , R ^13h , R ^13h2 , R ¹³ⁱ , R ^13j and R ^13k are each independently , which is the same or different and is a hydrogen atom, a hydroxyl group, a C _1-6 alkyl, a C _1-6 alkoxy, or a C _1-6 alkoxycarbonyl;
R ^10a , R ^10b , R ^10c , R ^10d , R ^10e , R ¹⁰ⁱ , R 10j , R ^10k , R ^10l , R ^10m , R ¹⁰ⁿ , R ^10s , R ^10s2 , R ^10t , R ^10t2 , R ^10u , ^{R 10u2} , R ^10v , R ^10w , R ^10x , R ^10y , R ^10z1 , R ^10z2 , R ^10z3 , R ^11a , R ^11b , R ^11c , R ^11d , R ^11e , R ¹¹ⁱ , R ^11j , R ^11k , R ^11l , R ^11m , R ^11q , R ^11q2 , R ^11r , R ^11r2 , R ^11s , R 11t , R ^11u , R ^11v , R ^11w , R ^12a , R ^12c , R ^12d , R ^12f , R ^12f2 , R ^12g , ^{R 12h , R12i} , ^R14 , ^{R15a , R15b} , R15c, R15d, R15e, ^R15f , ^R15f2 , ^R15g , ^{R15g2 , R15h} , ^R15i , ^R16a , ^{R16b , R16c , R16d} , R ^16e , R ^16f , R ^16f2 , R ^16g , R ^16h , R ^17a , R ^17b , R ^17c , and R ^17d are each independently the same or different and are hydrogen atom, C _1-6 alkyl (the C _1-6 alkyl may be substituted by 1 to 3 substituents, which may be the same or different, selected from hydroxyl group, cyano group, C _1-6 alkoxy, —NR ^18a R ^18b ), or C _1-6 is an alkoxycarbonyl,
R ^18a and R ^18b are each independently the same or different and are a hydrogen atom or C _1-6 alkyl.
In exemplary embodiments, any hydrogen of hydroxyl groups and amino groups in substituent groups α1 and β1 may be substituted with a protecting group.

In the present specification, the substituents in the case of "optionally substituted" preferably include the following substituents.
Substituent group α2 is preferably
1) halogen atom 2) hydroxyl group 3) carboxyl group 4) cyano group 5) C _1-6 alkyl 6) C _2-6 alkenyl 7) C _2-6 alkynyl 8) C _1-6 alkoxy 9) C _1-6 alkylthio 10) C _1-6 alkylcarbonyl 11) 4- to 10-membered non-aryl heterocyclic carbonyl (with the proviso that 5) to 11) each of the substituents are 1 to 5 identical or different groups selected from substituent group β2 may be substituted with a substituent of
12) C _3-10 alicyclic group 13) C _3-10 alicyclic oxy 14) C _6-10 aryloxy 15) 5- or 6-membered heteroaryloxy 16) 4-10 membered non-arylheterocyclic oxy 17) C _3-10 alicyclic thio 18) C _6-10 arylthio 19) 5- or 6-membered heteroarylthio 20) 4-10 membered non-aryl heterocyclic thio 21) C _6-10 aryl 22) C _{5 -10} heteroaryl23) 3- to 10-membered non-arylheterocycle24) _C3-10 alicyclic carbonyl25) _C6-10 arylcarbonyl26) 5- or 6-membered heteroarylcarbonyl27) 4- to 10-membered Each substituent of non-aryl heterocyclic carbonyl (12) to 27) may be substituted by 1 to 5 substituent groups β2 or the above 1) C _1-6 alkyl)
28)-NR ^10a R ^11a
29) —SO ₂ —NR ^10b R ^11b
30) —NR ^10c —C(=O)R ^11c
31) —NR ^12a —C(=O)NR ^10d R ^11d
32) —NR ^10e —SO ₂ —R ^11e
33) —NR ^12b —SO ₂ —NR ^10f R ^11f
34) —C(═O)NR ^{10 g} R ^{11 g}
35) -C (=NR ^13a )R ^10h
36) -C (=NR ^13b ) NR ¹⁰ⁱ R ^11h
37) -NR ^11f2 -C (=NR ^13c )R ^10g2
38) —NR ^12c —C (=NR ^13d ) —NR ^10j R ¹¹ⁱ
39) -C (=O) OR ^10k
are mentioned,
Substituent group β2 is preferably
1) halogen atom 2) hydroxyl group 3) cyano group 4) C _1-6 alkyl 5) C _3-10 alicyclic group 6) C _1-6 alkoxy 7) C _1-6 alkylthio 8) 5- or 6-membered hetero arylthio 9) C _6-10 aryl 10) C _6-10 heteroaryl 11) 4-10 membered non-aryl heterocycle 12) C _1-6 alkylcarbonyl 13) C _3-10 alicyclic carbonyl 14) C _{6 -10} arylcarbonyl 15) 5- or 6-membered heteroarylcarbonyl 16) 3- to 10-membered non-arylheterocyclic carbonyl 17) -NR ^15a R ^16a
18) -NR ^15b -C(=O)R ^16b
19) —NR ^17a —C(=O)NR ^15c R ^16c
20) -C(=O)NR ^15d R ^16d
21) -C (=NR ^13e )R ^15e
22) -C (=NR ^13f ) NR ^15f R ^16e
23) -NR ^16f -C (=NR ^13g ) R ^15g
24) —NR ^17b —C (=NR ^13h ) —NR ^15h R ^16g
25) -C (=N-OR ^13e2 ) R ^15e2
26) -C (=N-OR ^13f2 ) NR ^15f2 R ^16e2
27) -C (=O) OR ^10k
(However, each of the substituents 4) to 27) of the substituent group β2 is a halogen atom, a hydroxyl group, a cyano group, a carboxyl group, a C _1-6 alkoxy, a C _6-10 aryl, —NR ^18a R ^18b optionally substituted with 1 to 5 substituents selected from the group consisting of
R ^13a , R ^13a2 , R ^13b , R ^13b2 , R ^13c , R ^13d , R ^13e , R ^13e2 , R ^13f , R ^13f2 , R ^13g , and R ^13h are each independently the same or different, a hydrogen atom, a hydroxyl group, C _1-6 alkyl, C _1-6 alkoxy, or C _1-6 alkoxycarbonyl;
R ^10a , R ^10b , R ^10c , R ^10d , R ^10e , R ^10f , R ^10g , R ^10g2 , R ^10h , R ^10h2 , R ¹⁰ⁱ , R ¹⁰ⁱ² , R ^10j , R ^10k , R ^11a , R ^11b , R ^11c , R ^11d , R ^11e , R ^11f , R ^11f2 , R ^{11g , R 11h ,} R ^11h2 , R ¹¹ⁱ , R ^12a , R ^12b , R ^12c , R ^15a , R ^15b , R ^15c , R ^15d , R ^15e , R ^15e2 , ^{R15f , R15f2} , R15g, ^R15h , R16a, ^R16b , ^R16c , ^R16d , ^R16e , ^{R16e2 , R16f} , ^R16g , ^R17a and ^R17b are each independently The same or different, hydrogen atom, C _1-6 alkyl (the C _1-6 alkyl is the same or different selected from hydroxyl group, cyano group, C _1-6 alkoxy, —NR ^18a R ^18b , 1 to 3 optionally substituted by a substituent), or C _1-6 alkoxycarbonyl,
R ^18a and R ^18b are each independently the same or different and represent a hydrogen atom or C _1-6 alkyl.
In exemplary embodiments, any hydrogens of hydroxyl groups and amino groups in substituent groups α2 and β2 may be substituted with protecting groups.

More preferably, the substituents in the case of "optionally substituted" in the present specification include the following substituents.
Substituent group α3 is more preferably
1) halogen atom 2) hydroxyl group 3) cyano group 4) C _1-6 alkyl 5) C _1-6 alkyl 6) C _2-6 alkenyl 7) C _2-6 alkynyl 8) C _1-6 alkoxy 9) C _{1 -6} alkylthio 10) C _1-6 alkylcarbonyl 11) 3- to 10-membered non-aryl heterocyclic carbonyl (with the proviso that 4) to 11) each substituent is the same or different 1 selected from substituent group β3 optionally substituted with ~5 substituents)
12) C _3-10 alicyclic group 13) 5- or 6-membered heteroaryloxy 14) 4- to 10-membered non-arylheterocyclicoxy 15) 5- or 6-membered heteroarylthio 16) 4- to 10-membered non- arylheterocyclethio 17) C _6-10 aryl 18) C _5-10 heteroaryl 19) 3- to 10-membered non-arylheterocycle (provided that 12) to 19) each substituent has 1 to 5 substituents Group β3 or said 4) optionally substituted by C _1-6 alkyl)
20)-NR ^10a R ^11a
21) —NR ^11b —C(=O)R ^10b
22) —NR ^12a —C(=O)NR ^10c R ^11c
23) -C(=O)NR ^10d R ^11d
24) -C (=NR ^13a )R ^10e
25) -C (=NR ^13b ) NR ^10f R ^11e
26) —NR ^11f —C (=NR ^13c )R ^10g
27) —NR ^12b —C (=NR ^13d ) —NR ^10h R ^11g
28) -C (=O) OR ^10k
are mentioned,
Substituent group β3 is more preferably
1) a halogen atom,
2) a hydroxyl group,
3) a cyano group,
4) C _1-6 alkyl 5) C _3-10 alicyclic group 6) C _6-10 aryl 7) C _6-10 heteroaryl (provided that 4) to 7) each substituent is a halogen atom or a hydroxyl group , cyano group, carboxyl group, C _1-6 alkoxy, and C _6-10 aryl optionally substituted by 1 to 5 substituents)
8) —NR ^15a R ^16a ,
9) —NR ^15b —C(=O)R ^16b ,
10) —NR ^17a —C(=O)NR ^15c R ^16c ,
11) —C(=O)NR ^15d R ^16d ,
12) —C(=NR ^13e )R ^15e ,
13) -C (=NR ^13f ) NR ^15f R ^16e ,
14) —NR ^16f —C (=NR ^13g )R ^15g ,
15) —NR ^17b —C (=NR ^13h ) —NR ^15h R ^16g
16) -C (=O) OR ^10k
and
R ^13a , R ^13a2 , R ^13b , R ^13b2 , R ^13c , R ^13d , R ^13e , R ^13e2 , R ^13f , R ^13f2 , R ^13g , and R ^13h are each independently the same or different, a hydrogen atom, a hydroxyl group, C _1-6 alkyl, C _1-6 alkoxy, or C _1-6 alkoxycarbonyl;
R ^10a , R ^10b , R ^10c , R ^10d , R ^10e , R ^10f , R ^10e2 , R ^10f2 , R ^10g , R ^10h , R ^10k , R ^11a , R ^11b , R ^11c , R ^11d , R ^11e , R ^11e2 , R ^11f , R ^11g , R ^12a , R ^12b , R 15a , R ^15b , R ^15c , R ^15d , R ^15e , R ^15e2 , R ^15f , R ^15f2 , R ^15g , R ^15h , R ^16a , ^{R 16b ,} R ^16c , R ^16d , R ^16e , R ^16e2 , R ^16f , R ^16g , R ^17a and R ^17b are each independently the same or different and are hydrogen atom, C _1-6 alkyl (the C _1-6 alkyl is , a hydroxyl group, a cyano group, C _1-6 alkoxy, —NR ^18a optionally substituted by 1 to 3 substituents which are the same or different and selected from R ^18b ), or C _1-6 alkoxycarbonyl;
R ^18a and R ^18b are each independently the same or different and are a hydrogen atom or C _1-6 alkyl.
In exemplary embodiments, any hydrogen of hydroxyl and amino groups in substituent groups α3 and β3 may be substituted with a protecting group.

In an exemplary embodiment, the hydroxyl groups in the above substituent groups (eg, α (α1 etc.), β (β1 etc.), I-VI) may be further protected with a silyl protecting group. In an exemplary embodiment, the amino groups in the above substituent groups (eg, α (α1, etc.), β (β1, etc.), I-VI) may be further protected with a nitrogen protecting group.

As used herein, “C _1-6 ” means having 1 to 6 carbon atoms. The same applies to other numbers. For example, “C _1-4 ” means that the number of carbon atoms is 1 to 4, and “C _1-3 ” means that the number of carbon atoms is 1 to 3. means. In the present specification, descriptions with carbon number limitations are merely preferred numerical ranges, and the present disclosure is intended to include groups having substituents with carbon numbers other than the specified carbon number within the scope of the present disclosure. .

As used herein, a "hydrocarbon group" is also referred to as a hydrocarbyl group, a group generated by removing at least one hydrogen from a "hydrocarbon" containing at least one carbon and at least one hydrogen. (group).

As used herein, the term "functional group" refers to any group that imparts some functionality, such as a carboxyl group, nitrile group, carbonyl group, hydroxy group, amino group, imino group, nitro group, and halogen group. In addition, alkyl groups are also included, and in a broader sense, groups formed by bonds such as acid anhydrides, ester bonds, amide bonds and ether bonds are also included.

As used herein, the term “heteroatom” refers to atoms other than carbon atoms and hydrogen atoms, such as oxygen atoms, nitrogen atoms, sulfur atoms, and the like. A group containing a heteroatom is a hetero group (e.g., a heteroaryl group (meaning that an aryl group contains at least a heteroatom)) or a hetero group (e.g., a heterocyclic group (a ring group ( It means that the carbocyclic group) contains at least one heteroatom.)) and the like.

As used herein, the term "halogen atom" means an atom belonging to the halogen group, such as a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. A fluorine atom or a chlorine atom is preferred. More preferably, it is a fluorine atom. A "halogen atom" may also be referred to as "halogen" or "halo".

As used herein, a "hydroxyl group" is a monovalent group of --OH. This group is sometimes called a "hydroxy group" or "hydroxy".

As used herein, a "carboxyl group" is a monovalent group of --COOH. This group is sometimes referred to as a "carboxy group," "carboxy," or "carboxyl."

As used herein, a “cyano group” is a monovalent group of —CN.

As used herein, "amino" is a monovalent group of _-NH2 . This group is sometimes called an "amino group".

As used herein, "alkyl" means a straight or branched chain saturated aliphatic hydrocarbon group. "C _1-12 alkyl" is an alkyl group having 1 to 12 carbon atoms, examples include C _1-6 alkyl, heptyl, isoheptyl, octyl, isooctyl, nonyl, isononyl, decyl, isodecyl, undecyl, isundecyl , dodecyl, isododecyl, and the like, but are not limited thereto. A “C _1-12 alkyl” is an alkyl group having 1 to 12 carbon atoms. "C _1-6 alkyl" is an alkyl group having 1 to 6 carbon atoms, preferred examples include "C _1-4 alkyl", more preferably "C _1-3 alkyl", More preferably, it is “C _1-2 alkyl”. Specific examples of “C _1-4 alkyl” include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl and the like. Specific examples of "C _1-6 alkyl" include, but are limited to, C _1-4 alkyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, 1,2-dimethylpropyl, n-hexyl and the like. not. Specific examples of "C _1-12 alkyl" include C _1-6 alkyl, n-heptyl, isoheptyl, n-octyl, isooctyl, n-nonyl, n-decanyl, n-undecyl, n-dodecyl and the like. but not limited to these.

As used herein, "alkenyl" means a straight or branched chain unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon double bond. "C _2-12 alkenyl" is an alkenyl group having 2 to 12 carbon atoms, examples of which include heptenyl, isoheptenyl, octenyl, isooctenyl, nonenyl, isononenyl, decenyl, isodecenyl, undecenyl, isoundecenyl, dodecenyl, isododecenyl, and the like. include, but are not limited to. “C _2-6 alkenyl” is an alkenyl group having 2 to 6 carbon atoms, and preferred examples include “C _2-4 alkenyl”. Specific examples of "C _2-6 alkenyl" include vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl etc., but not limited to these.

As used herein, "alkynyl" means a straight or branched chain unsaturated aliphatic hydrocarbon group containing at least one carbon-carbon triple bond. “C _2-12 alkynyl” is an alkynyl group having 2 to 12 carbon atoms, examples of which include heptynyl, isoheptynyl, octynyl, isooctynyl, nonynyl, isononynyl, decynyl, isodecynyl, undecynyl, isoundecynyl, dodecynyl, isododecynyl and the like. Examples include, but are not limited to: “C _2-6 alkynyl” is an alkynyl group having 2 to 6 carbon atoms, and preferred examples include “C _2-4 alkynyl”. Specific examples of "C _2-6 alkynyl" include ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 1-methyl-2-propynyl, 3-butynyl, 1-pentynyl, 1-hexynyl and the like. include but are not limited to:

As used herein, "aryl" means a monovalent group of a monocyclic or bicyclic aromatic hydrocarbon ring, and "C _6-10 aryl" means an aryl group having 6 to 10 carbon atoms. do. Examples of "aryl" include, but are not limited to, _C6 aryl, _C10 aryl, and the like. Specific examples of _C6 aryl include, but are not limited to, phenyl and the like. Specific examples of C ₁₀ aryl include, but are not limited to, 1-naphthyl, 2-naphthyl, and the like.

An aryl group as a substituent or part thereof may be fused with an alicyclic group. For example, a phenyl group may be fused with a cyclohexane ring to form a 1,2,3,4-tetrahydronaphthalenyl group, where any of the possible carbon atoms on the benzene ring are Or it binds to a group or an atom thereof close to the mother skeleton. Aryl groups include 5,6,7,8-tetrahydronaphthalen-1-yl, 5,6,7,8-tetrahydronaphthalen-2-yl.

As used herein, "arylalkyl" means alkyl substituted with at least one aryl. “C _6-10 arylC _1-6 alkyl” means C _1-6 alkyl substituted with at least one C _6-10 aryl. Specific examples of C _6-10 arylC _1-6 alkyl include benzyl (ie phenyl-CH ₂ —), phenethyl (ie phenyl-CH ₂ CH ₂ —), 1-phenylethyl, naphthalen-1-ylmethyl , naphthalen-2-ylmethyl, 2-(naphthalen-1-yl)ethyl, 2-(naphthalen-2-yl)ethyl, 1-(naphthalen-1-yl)ethyl, 1-(naphthalen-2-yl)ethyl etc., but not limited to these.

As used herein, "(optionally substituted amino)-arylalkyl" means an arylalkyl substituted with an optionally substituted amino group, wherein the alkyl group or the aryl group, or Both of them are substituted with amino groups. The amino group of the arylalkyl group may be unsubstituted or may have 1, 2 or 3 substituents, such as optionally substituted alkyl (eg unsubstituted C _1-6 alkyl, C _3-6 cycloalkyl-C _1-6 alkyl, C _3-6 cycloalkylcarbonyl, etc.).
Examples of (optionally substituted amino)-C _6-10 arylC _1-6 alkyl include (di(alkyl)amino)benzyl, ((cycloalkylalkyl)amino)benzyl, ((cycloalkylcarbonyl) amino)benzyl, ((carbamoylalkyl)carbonylamino)benzyl, ((carboxyalkyl)carbonyl)aminobenzyl, (di(alkyl)amino)naphthalenylmethyl, ((cycloalkylalkyl)amino)naphthalenylmethyl, ( (Cycloalkylcarbonyl)amino)naphthalenylmethyl, ((carbamoylalkyl)carbonylamino)naphthalenylmethyl, or ((carboxyalkyl)carbonyl)aminonaphthalenylmethyl, and the like, but are not limited thereto.

As used herein, the aryl portion of "arylthio" is synonymous with the above aryl. “C _6-10 arylthio” preferably includes “C ₆ or C ₁₀ arylthio”. Specific examples of “C _6-10 aryloxy” include, but are not limited to, phenylthio, 1-naphthylthio, 2-naphthylthio and the like.

As used herein, "arylsulfonyl" means sulfonyl substituted with the above "aryl". “C _6-10 arylsulfonyl” is preferably “C ₆ or C ₁₀ arylsulfonyl”. Specific examples of “C _6-10 arylsulfonyl” include, but are not limited to, phenylsulfonyl, 1-naphthylsulfonyl, 2-naphthylsulfonyl and the like.

As used herein, "heteroaryl" is a monocyclic or bicyclic aromatic heterocycle containing from 1 to 4 identical or different heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur atoms. means a monovalent group of

As used herein, "5- or 6-membered heteroaryl" means from 5 to 6 atoms, including 1 to 4 identical or different heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur atoms. means a monovalent group of a monocyclic aromatic heterocyclic ring. Specific examples of "5- or 6-membered heteroaryl" include pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, tetrazolyl, pyridyl, furyl, pyridazinyl, pyrimidinyl, pyrazinyl and the like. include, but are not limited to.

As used herein, "5- to 10-membered heteroaryl" consists of 5 to 10 atoms containing 1 to 4 identical or different heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur atoms. It means a monovalent radical of a monocyclic or bicyclic aromatic heterocycle. Specific examples of "5- to 10-membered heteroaryl" include 5- or 6-membered heteroaryl, quinolyl, isoquinolyl, naphthyridinyl, quinoxalinyl, cinnolinyl, quinazolinyl, phthalazinyl, imidazopyridyl, imidazothiazolyl, imidazooxazolyl, benzothiazolyl , benzoxazolyl, benzimidazolyl, indolyl, isoindolyl, indazolyl, pyrrolopyridyl, thienopyridyl, furopyridyl, benzothiadiazolyl, benzoxadiazolyl, pyridopyrimidinyl, benzofuryl, benzothienyl, benzo[1,3]dioxole, thienofuryl, chromenyl , chromanyl, coumarinyl, quinolonyl, and the like, but are not limited thereto.

As used herein, "heteroarylalkyl" means alkyl substituted with at least one heteroaryl. “5- to 10-membered heteroaryl C _1-6 alkyl” means C _1-6 alkyl substituted with at least one 5- to 10-membered heteroaryl. Specific examples of 5- to 10-membered heteroaryl C _1-6 alkyl include pyridin-2-ylmethyl, pyridin-4-ylmethyl, 2-(quinolin-8-yl)ethyl, 2-(quinolin-5-yl)ethyl , 2-(quinoxalin-5-yl)ethyl, 1H-indol-3-ylmethyl, 2-(1H-indol-3-yl)ethyl and the like, but are not limited thereto.

As used herein, the term "alicyclic group" means a monocyclic, bicyclic or tricyclic non-aromatic hydrocarbon ring monovalent group, which partially has an unsaturated bond, partially Also included are those having a bridged structure, those partially spiroified, and those having one or two or more carbonyl structures. "Alicyclic group" includes cycloalkyl, cycloalkenyl, and cycloalkynyl. The “C _3-20 alicyclic group” is preferably a “C _3-10 alicyclic group”, more preferably a “C _3-6 alicyclic group”. Specific examples of the "C _3-20 alicyclic group" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclohexadinyl, cycloheptazinyl, cyclooctazinyl, adamantyl, norbornyl and the like. Examples include, but are not limited to:

A cycloaliphatic group may be a fused ring of a non-aryl ring and an aryl and/or heteroaryl ring. For example, a cycloalkyl fused to a C _6-10 aryl or a 5- or 6-membered heteroaryl is included in an alicyclic group. Examples of fused alicyclic groups include one hydrogen from 1,2,3,4-tetrahydronaphthalene, indane, 1,2,3,4-tetrahydroanthracene, and 5,6,7,8-tetrahydroquinoline. Examples include monovalent groups from which atoms have been removed, and specific examples include 1,2,3,4-tetrahydronaphthalen-1-yl, 1,2,3,4-tetrahydronaphthalen-2-yl, indane- 1-yl, indan-2-yl, 5,6,7,8-tetrahydroquinolin-5-yl, 5,6,7,8-tetrahydroquinolin-6-yl and the like. A fused alicyclic group is attached to the backbone through any one of the possible ring atoms on the non-aryl ring.

In the present specification, the "C _3-10 alicyclic group" is a substituent in which the "C _3-10 alicyclic group" of the above "C _3-20 alicyclic group" is a monovalent group. means

As used herein, "alicyclic oxy" means (alicyclic group)-O- group, and the alicyclic moiety is synonymous with alicyclic group. "C _3-6 cycloaliphatic oxy" means a (C _3-6 cycloaliphatic group)-O- group, wherein said C _3-6 cycloaliphatic moiety comprises a C _3-6 cycloaliphatic group and Synonymous. "C _3-6 alicyclic oxy" is preferably "C _3-5 alicyclic oxy". Specific examples of “C _3-6 alicyclic oxy” include, but are not limited to, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy and the like.

As used herein, "alicyclic carbonyl" means a carbonyl substituted with the above "alicyclic group". The “C _3-10 alicyclic carbonyl” is preferably “C _3-6 alicyclic carbonyl”. Specific examples of “C _3-10 alicyclic carbonyl” include, but are not limited to, cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl and the like.

As used herein, “alicyclic thio” means (alicyclic group)—S— group, and the alicyclic moiety is as defined above. “C _3-10 alicyclic thio” is preferably “C _3-6 alicyclic thio”. Specific examples of “C _3-6 alicyclic thio” include, but are not limited to, cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio and the like.

As used herein, "alicyclic sulfonyl" means a sulfonyl group substituted with the above "alicyclic group". “C _3-10 alicyclic sulfonyl” is preferably “C _3-6 alicyclic sulfonyl”. Specific examples of “C _3-10 alicyclic sulfonyl” include, but are not limited to, cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl and the like.

As used herein, "cycloalkyl" means a non-aromatic saturated hydrocarbon ring group, partially bridged, partially spirolated, and having one or two or more carbonyl structures Also includes those with “C _3-20 cycloalkyl” means monocyclic or bicyclic cycloalkyl having 3 to 20 carbon atoms. “C _3-6 cycloalkyl” means monocyclic cycloalkyl having 3 to 6 carbon atoms. Specific examples of C _3-6 cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. “C _3-10 cycloalkyl” means monocyclic or bicyclic cycloalkyl having 3 to 10 carbon atoms. Specific examples of C _3-10 cycloalkyl include C _3-6 cycloalkyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, bicyclo[4.1.0]heptyl, bicyclo[3.3.0]octyl, bicyclo Examples include, but are not limited to, [4.2.0]octyl, bicyclo[4.3.0]nonyl, decahydronaphthyl, and the like.

A cycloalkyl group as a substituent or part thereof may be fused with an aryl and/or heteroaryl ring. For example, a cyclohexyl group may be fused with a benzene ring to form a 1,2,3,4-tetrahydronaphthalenyl group, where any of the possible carbon atoms on the cyclohexane ring are Or it binds to a group or an atom thereof close to the mother skeleton. Cycloalkyl groups are 1,2,3,4-tetrahydronaphthalen-1-yl, 1,2,3,4-tetrahydronaphthalen-2-yl, indan-1-yl, indan-2-yl, 5,6 , 7,8-tetrahydroquinolin-5-yl, 5,6,7,8-tetrahydroquinolin-6-yl.

As used herein, "cycloalkylalkyl" means alkyl substituted with at least one cycloalkyl. “C _3-10 cycloalkylC _1-6 alkyl” means C _1-6 alkyl substituted with at least one C _3-10 cycloalkyl, “C _3-6 cycloalkylC _1-6 alkyl” means C _1-6 alkyl substituted with at least one C _3-6 cycloalkyl. Specific examples of C _3-6 cycloalkyl C _1-6 alkyl include cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, 2-cyclopropylethyl, 2-cyclobutylethyl, 2-cyclopentylethyl, 2- Examples include, but are not limited to, cyclohexylethyl, 3-cyclopropylpropyl, 3-cyclobutylpropyl, 3-cyclopentylpropyl, 3-cyclohexylpropyl and the like. Specific examples of C _3-10 cycloalkylC _1-6 alkyl include C _3-6 cycloalkylmethyl, C _3-6 cycloalkylethyl, cycloheptylmethyl, cycloheptylethyl, cyclooctylmethyl, cyclooctylethyl, cyclo nonylmethyl, cyclononylethyl, cyclodecylmethyl, cyclodecylethyl and the like, but are not limited thereto.

As used herein, "heterocycloalkyl" is composed of 3 or more atoms, including the same or different 1 or 2 or more heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur atoms. means a non-aromatic saturated or partially unsaturated heterocyclic ring, including those with partially bridged structures and those that are partially spiroified. "Heterocycloalkyl" includes "non-arylheterocycles". Heterocycloalkyls can have structures in which a non-aromatic heterocyclic ring is fused with an aryl ring and/or a heteroaryl ring.

As used herein, "non-arylheterocycle" refers to three or more atoms containing one or two or more heteroatoms that are the same or different and selected from the group consisting of oxygen, nitrogen and sulfur atoms. means a monocyclic or bicyclic non-aromatic heterocycle composed of saturated non-aryl heterocycles, partially unsaturated bonds, partially bridged structures and partially spiro including those that have been converted. A non-arylheterocycle may form a fused ring with an aryl or heteroaryl. For example, it is included in heterocycle when it is fused with C _6-10 aryl or 5- or 6-membered heteroaryl. It may also contain one or more carbonyls, thiocarbonyls, sulfinyls or sulfonyls to make up the non-aryl heterocycle, e.g. lactams, thiolactams, lactones, thiolactones, cyclic imides , cyclic carbamate, cyclic thiocarbamate, and other cyclic groups are also included in the non-aryl heterocycle. Here, the oxygen atom of carbonyl, sulfinyl and sulfonyl and the sulfur atom of thiocarbonyl are not included in the number of ring members (ring size) and the number of heteroatoms constituting the ring.

As used herein, the term "4- to 10-membered non-aryl heterocycle" means a substituent in which the "4- to 10-membered non-aryl heterocycle" of the above-mentioned "non-aryl heterocycle" is a monovalent group. do.

As used herein, the non-aryl heterocyclic moiety of "non-aryl heterocyclic oxy" is synonymous with the above-mentioned "4- to 10-membered non-aryl heterocyclic ring". The “4- to 10-membered non-arylheterocyclic oxy” is preferably “4- to 6-membered non-arylheterocyclic oxy”. Specific examples of "4- to 10-membered non-arylheterocyclic oxy" include, but are limited to, tetrahydrofuranyloxy, tetrahydropyranyloxy, azetidinyloxy, pyrrolidinyloxy, piperidinyloxy, and the like. not.

As used herein, the nonarylheterocyclic portion of "nonarylheterocyclicthio" is synonymous with the above "nonarylheterocyclic ring". The "4- to 10-membered non-arylheterocyclic thio" is preferably "4- to 6-membered non-aryl-heterocyclic thio". Specific examples of the "4- to 10-membered non-arylheterocyclic thio" include, but are not limited to, tetrahydropyranylthio, piperidinylthio and the like.

As used herein, "nonarylheterocyclic carbonyl" means a carbonyl group substituted with the above "nonarylheterocyclic". The "4- to 10-membered non-aryl heterocyclic carbonyl" is preferably "4- to 6-membered non-aryl heterocyclic carbonyl". Specific examples of "4- to 10-membered non-arylheterocyclic carbonyl" include, but are not limited to, azetidinylcarbonyl, pyrrolidinylcarbonyl, piperidinylcarbonyl, morpholinylcarbonyl and the like.

As used herein, "nonarylheterocyclesulfonyl" means a sulfonyl group substituted with the above "nonarylheterocycle". The “4- to 10-membered non-arylheterocyclesulfonyl” is preferably “4- to 6-membered non-arylheterocyclesulfonyl”. Specific examples of "4- to 10-membered non-arylheterocyclic sulfonyl" include, but are not limited to, azetidinylsulfonyl, pyrrolidinylsulfonyl, piperidinylsulfonyl, morpholinylsulfonyl and the like.

As used herein, "5- or 6-membered heterocycloalkyl" and "5- to 6-membered heterocycloalkyl" are the same or different 1 or 2 or more hetero atoms selected from oxygen, nitrogen and sulfur atoms. It means heterocycloalkyl composed of 5 to 6 ring atoms, including atoms.

As used herein, "heterocycloalkylalkyl" means alkyl substituted with at least one heterocycloalkyl.

As used herein, "alkylcarbonyl" is a monovalent radical of -C(=O)-alkyl. Preferred examples of alkylcarbonyl include C _1-6 alkylcarbonyl. Specific examples of C _1-6 alkylcarbonyl include acetyl (CH ₃ C(=O)-), n-propanoyl (CH ₃ CH ₂ C(=O)-), n-butanoyl (CH ₃ CH ₂ CH ₂ C(=O)-), n-pentanoyl (CH ₃ (CH ₂ ) ₃ C(=O)-), n-hexanoyl (CH ₃ (CH ₂ ) ₄ C(=O)-), n-heptanoyl ( CH ₃ (CH ₂ ) ₅ C(=O)—) and the like, but are not limited thereto.

As used herein, "alkoxy" is a monovalent radical of -O-alkyl. Preferred examples of alkoxy include C _1-6 alkoxy (ie C _1-6 alkyl-O-), C _1-4 alkoxy (ie C _1-4 alkyl-O-) and the like. Specific examples of C _1-4 alkoxy include methoxy (CH ₃ O—), ethoxy (CH ₃ CH ₂ O—), n-propoxy (CH ₃ (CH ₂ ) ₂ O—), isopropoxy ((CH ₃ ) ₂ CHO-), n-butoxy (CH ₃ (CH ₂ ) ₃ O-), isobutoxy ((CH ₃ ) ₂ CHCH ₂ O-), tert-butoxy ((CH ₃ ) ₃ CO-), sec-butoxy (CH ₃ CH ₂ CH(CH ₃ )O—) and the like. Specific examples of C _1-6 alkoxy include C _1-4 alkoxy, n-pentyloxy (CH ₃ (CH ₂ ) ₄ O-), isopentyloxy ((CH ₃ ) ₂ CHCH ₂ CH ₂ O-), neopentyloxy ((CH ₃ ) ₃ CCH ₂ O—), tert-pentyloxy (CH ₃ CH ₂ C(CH ₃ ) ₂ O—), 1,2-dimethylpropoxy (CH ₃ CH(CH ₃ )CH( CH ₃ )O—) and the like, but are not limited thereto.

As used herein, "alkoxycarbonyl" is a monovalent radical of -C(=O)-O-alkyl. Examples of alkoxycarbonyl include, but are not limited to, C _1-6 alkoxycarbonyl, preferably C _1-4 alkoxycarbonyl. Specific examples of C _1-4 alkoxycarbonyl include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, isobutoxycarbonyl and the like. Specific examples of C _1-6 alkoxycarbonyl include C _1-4 alkoxycarbonyl, n-pentyloxycarbonyl, isopentyloxycarbonyl, neopentyloxycarbonyl, tert-pentyloxycarbonyl, 1,2-dimethylpropyloxycarbonyl, Examples include, but are not limited to, n-hexyloxycarbonyl and the like.

As used herein, "alkoxycarbonylamino" is a monovalent radical of -NH-C(=O)-O-alkyl. Examples of alkoxycarbonylamino include, but are not limited to, C _1-6 alkoxycarbonylamino, preferably C _1-4 alkoxycarbonylamino. Specific examples of C _1-4 alkoxycarbonylamino include methoxycarbonylamino, ethoxycarbonylamino, n-propoxycarbonylamino, isopropoxycarbonylamino, n-butoxycarbonylamino, sec-butoxycarbonylamino, tert-butoxycarbonylamino, and isobutoxycarbonylamino. Specific examples of C _1-6 alkoxycarbonylamino include C _1-4 alkoxycarbonylamino, n-pentyloxycarbonylamino, isopentyloxycarbonylamino, neopentyloxycarbonylamino, tert-pentyloxycarbonylamino, 1,2 -dimethylpropyloxycarbonylamino, n-hexyloxycarbonylamino, and the like, but are not limited to these.

As used herein, "haloalkyl" refers to a monovalent halogenated alkyl group in which one or more hydrogens on the alkyl group have been replaced with a halogen. The term "perhaloalkyl" also means a haloalkyl in which all hydrogens on the alkyl group have been replaced with halogens. For example, perfluoroethyl is -CF ₂ CF ₃ and perchloro-n-propyl is -CCl ₂ CCl ₂ CCl ₃ . Examples of haloalkyl include C _1-6 haloalkyl, C _1-4 haloalkyl, C _1-3 haloalkyl and the like. Specific examples of C _1-3 alkyl include fluoromethyl, chloromethyl, bromomethyl, difluoromethyl, dichloromethyl, dibromomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, fluorochloromethyl, difluorochloromethyl, fluorodichloromethyl , fluoroethyl, chloroethyl, bromoethyl, trifluoroethyl, trichloroethyl, tribromoethyl, perfluoroethyl, perchloroethyl, perbromoethyl, perfluoropropyl, perchloropropyl, perbromopropyl, perfluoroisopropyl, perchloroisopropyl, perbromo Examples include, but are not limited to, isopropyl and the like. Specific examples of C _1-4 alkyl include, but are not limited to, C _1-3 haloalkyl, perfluorobutyl, perchlorobutyl, perbromobutyl, perfluoroisobutyl, perfluoro-t-butyl and the like. Specific examples of C _1-6 alkyl include C _1-4 haloalkyl, perfluoro-n-pentyl, perfluoroisopentyl, perfluoroneopentyl, perfluorotert-pentyl, perfluoro-1,2-dimethylpropyl, etc. It is not limited to these.

As used herein, “haloalkoxy” and “haloalkyloxy” are —O-haloalkyl monovalent radicals in which one or more hydrogens on the alkyl group have been replaced with halogen. Also, the term "perhaloalkoxy" means a haloalkoxy in which all hydrogens on the alkyl group have been replaced with halogens. For example, perfluoroethoxy is -OCF ₂ CF ₃ and perchloro-n-propoxy is -OCCl ₂ CCl ₂ CCl ₃ . Preferred examples of haloalkoxy include C _1-6 haloalkoxy, C _1-4 haloalkoxy, C _1-3 haloalkoxy and the like. Specific examples of C _1-3 alkoxy include fluoromethoxy, chloromethoxy, bromomethoxy, difluoromethoxy, dichloromethoxy, dibromomethoxy, trifluoromethoxy, trichloromethoxy, tribromomethoxy, fluorochloromethoxy, difluorochloromethoxy, fluorodichloro Methoxy, fluoroethoxy, chloroethoxy, bromoethoxy, trifluoroethoxy, trichloroethoxy, tribromoethoxy, perfluoroethoxy, perchloroethoxy, perbromoethoxy, perfluoropropoxy, perchloropropoxy, perbromopropoxy, perfluoroisopropoxy, perchloro Examples include, but are not limited to, isopropoxy, perbromoisopropoxy, and the like. Specific examples of C _1-4 alkoxy include, but are not limited to, C _1-3 haloalkoxy, perfluorobutoxy, perchlorobutoxy, perbromobutoxy, perfluoroisobutoxy, perfluoro-t-butoxy and the like. Specific examples of C _1-6 alkoxy include C _1-4 haloalkoxy, perfluoro-n-pentyloxy, perfluoroisopentyloxy, perfluoroneopentyloxy, perfluorotert-pentyloxy, perfluoro-1,2-dimethylpropoxy and the like. include, but are not limited to.

As used herein, "alkylsulfonyl" means a sulfonyl group substituted with the above "alkyl". “C _1-6 alkylsulfonyl” is preferably “C _1-4 alkylsulfonyl”. Specific examples of “C _1-6 alkylsulfonyl” include, but are not limited to, methylsulfonyl, propionylsulfonyl, butyrylsulfonyl and the like.

In the present specification, the alkyl portion of "alkylthio" has the same meaning as the above alkyl. Examples of “C _1-6 alkylthio” include “C _1-4 alkylthio”, preferably “C _1-3 alkylthio”. Specific examples of "C _1-6 alkylthio" include methylthio, ethylthio, n-propylthio, n-butylthio, isopropylthio, isobutylthio, tert-butylthio, sec-butylthio, isopentylthio, neopentylthio and tert-pentylthio. , 1,2-dimethylpropylthio, and the like, but are not limited thereto.

As used herein, "arylcarbonyl" is a -C(=O)-aryl monovalent group. Preferred examples of arylcarbonyl include C _6-10 arylcarbonyl. Specific examples of C _6-10 arylcarbonyl include, but are not limited to, benzoyl (ie, phenyl-C(=O)-), 1-naphthylcarbonyl, 2-naphthylcarbonyl, and the like.

As used herein, the aryl portion of "aryloxy" has the same definition as the above aryl. “C _6-10 aryloxy” preferably includes “C ₆ or C ₁₀ aryloxy”. Specific examples of the “C _6-10 aryloxy group” include, but are not limited to, phenoxy group, 1-naphthyloxy group, 2-naphthyloxy group and the like.

As used herein, "heteroarylcarbonyl" is a -C(=O)-heteroaryl monovalent radical.

As used herein, "heteroarylcarbonyl group" means a carbonyl group substituted with the above "heteroaryl". Specific examples of the "5- or 6-membered heteroarylcarbonyl group" include a pyrazoylcarbonyl group, a triazolylcarbonyl group, a thiazolylcarbonyl group, a thiadiazoylcarbonyl group, a pyridylcarbonyl group, a pyridazoylcarbonyl group, and the like. include but are not limited to:

As used herein, the heteroaryl portion of the "heteroaryloxy group" is synonymous with the above-mentioned "heteroaryl". The 5- or 6-membered heteroaryl portion of the "5- or 6-membered heteroaryloxy group" is synonymous with the "5-membered heteroaryl" or "6-membered heteroaryl", respectively. Specific examples of the "5- or 6-membered heteroaryloxy group" include a pyrazoyloxy group, a triazolyloxy group, a thiazolyloxy group, a thiadiazoyloxy group, a pyridyloxy group, a pyridazoyloxy group, and the like. include but are not limited to:

As used herein, the heteroaryl part of the "heteroarylthio group" is synonymous with the above-mentioned "heteroaryl". The 5- or 6-membered heteroaryl portion of the "5- or 6-membered heteroarylthio group" is synonymous with "5-membered heteroaryl" or "6-membered heteroaryl", respectively. Specific examples of the "5- or 6-membered heteroarylthio group" include, but are not limited to, a pyrazoylthio group, a triazolylthio group, a thiazolylthio group, a thiadiazoylthio group, a pyridylthio group, a pyridazoylthio group, and the like.

As used herein, the heteroaryl portion of the "heteroarylsulfonyl group" is synonymous with the above-mentioned "heteroaryl". A "5- or 6-membered heteroarylsulfonyl group" means a sulfonyl group substituted with the above "5- or 6-membered heteroaryl". Specific examples of the "5- or 6-membered heteroarylsulfonyl group" include a pyrazoylsulfonyl group, a triazolylsulfonyl group, a thiazolylsulfonyl group, a thiadiazoylsulfonyl group, a pyridylsulfonyl group, a pyridazoylsulfonyl group, and the like. include but are not limited to:

As used herein, "acyl" means a monovalent group -C(=O)-R _acyl , where R _acyl is hydrogen, optionally substituted alkyl, optionally substituted is optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted heterocycloalkyl. Specific examples of acyl include, but are not limited to, formyl, and the illustrated groups of alkylcarbonyl, arylcarbonyl, and heteroarylcarbonyl, and the like.

As used herein, an "optionally substituted carbonyl" group refers to a monovalent group -C(=O)- (hydrogen or any group selected from the group of substituents described herein) means Examples of "optionally substituted carbonyl" groups include formyl, optionally substituted carbamoyl, alkylcarbonyl, alkoxycarbonyl, alkenylcarbonyl, alkenyloxycarbonyl, alkynylcarbonyl, alkynyloxycarbonyl, arylcarbonyl , aryloxycarbonyl, cycloalkylcarbonyl, cycloalkyloxycarbonyl, heteroarylcarbonyl, heteroaryloxycarbonyl, heterocycloalkylcarbonyl, heterocycloalkyloxycarbonyl, and the like. A carbonyl group substituted with hydrogen is a formyl group. A carbonyl group substituted with amino is a carbamoyl group.

As used herein, an "optionally substituted oxy" group refers to a monovalent radical of -O- (hydrogen or any group selected from the group of substituents described herein). Examples of "optionally substituted oxy" groups include hydroxy, optionally substituted alkyloxy, alkenyloxy, alkynyloxy, aryloxy, heteroaryloxy, heterocycloalkyloxy, alkylcarbonyloxy , alkenylcarbonyloxy, alkynylcarbonyloxy, arylcarbonyloxy, heteroarylcarbonyloxy, heterocycloalkylcarbonyloxy, and the like. An oxy group substituted with hydrogen is a hydroxy group.

As used herein, "carbamoyl" is a monovalent group of -C(=O) _-NH2 .

As used herein, a "guanidino" group is a monovalent group of -NH-C(=NH) _-NH2 .

As used herein, the term "a group substituted with a certain substituent" means that the group is substituted with at least one substituent. For example, “hydroxy-substituted C _1-6 alkyl” means that the C _1-6 alkyl is substituted with at least one hydroxy.

As used herein, "carbamoyl-substituted C _1-6 alkyl" is C _1-6 alkyl substituted with at least one -C(=O)-NH ₂ group. Examples of "carbamoyl-substituted C _1-6 alkyl" include carbamoyl-substituted C _1-4 alkyl, 6-amino-6-oxohexyl (ie H ₂ NC(=O)-(CH ₂ ) ₅ -, or carbamoylpentyl), 7-amino-7-oxoheptyl (ie, H ₂ NC(=O)-(CH ₂ ) ₆ -, or carbamoylhexyl), and the like, but are not limited thereto. Specific examples of “carbamoyl-substituted C _1-4 alkyl” include 2-amino-2-oxoethyl (ie, H ₂ NC(═O)—CH ₂ —, or carbamoylmethyl), 3-amino-3- oxopropyl (ie, H ₂ NC(=O)--CH ₂ CH ₂ --, or carbamoylethyl), 4-amino-4-oxobutyl (ie, H ₂ NC(=O)--(CH ₂ ) ₃ --, or carbamoylpropyl), 5-amino-5-oxopentyl (ie, H ₂ NC(═O)—(CH ₂ ) ₄ —, or carbamoylbutyl), and the like.

が挙げられる。本明細書において「グアニジノ」と「アミジノアミノ」は同義である。 As used herein, "guanidino-substituted alkyl" or "guanidino-substituted alkyl" is an alkyl substituted with at least one -NH-C(=NH) _-NH2 group, wherein the guanidino group A nitrogen atom may be protected with a nitrogen protecting group (eg, a tert-butoxycarbonyl group). Examples of “guanidino-substituted C _1-6 alkyl” include, but are not limited to, “guanidino-substituted C _1-4 alkyl” and the like. Specific examples of "guanidino-substituted C _1-4 alkyl" include (guanidino)methyl, 2-(guanidino)ethyl, 3-(guanidino)propyl, 4-(guanidino)butyl and the like, and these include Not limited. Specific examples of "guanidino-substituted C _1-6 alkyl" include, but are not limited to, guanidino-substituted C _1-4 alkyl, 5-(guanidino)pentyl, 6-(guanidino)hexyl and the like. . Examples of guanidino groups protected with nitrogen protecting groups are:

are mentioned. As used herein, "guanidino" and "amidinoamino" are synonymous.

As used herein, a "carboxy-substituted alkyl" is an alkyl substituted with at least one -COOH group. Examples of "carboxy-substituted C _1-6 alkyl" include, but are not limited to, carboxy-substituted C _1-4 alkyl, 5-carboxypentyl, 6-carboxyhexyl, and the like. Specific examples of “carboxy-substituted C _1-4 alkyl” include, but are not limited to, carboxymethyl, 2-carboxyethyl, 3-carboxypropyl, 4-carboxybutyl, and the like.

As used herein, "arylalkyl substituted with alkyl-substituted amino" is arylalkyl substituted with at least one alkyl-substituted amino. Specific examples of C _1-6 alkyl-substituted amino include -NH(CH ₃ ), -N(CH ₃ ) ₂ , -NH(CH ₂ CH ₃ ), -N(CH ₂ CH ₃ ) ₂ , -NH( (CH ₂ ) ₂ CH ₃ ), —N((CH ₂ ) ₂ CH ₃ ) ₂ , —NH(CH(CH ₃ ) ₂ ), —N(CH(CH ₃ ) ₂ ) ₂ , —NH((CH ₂ ) ₃ CH ₃ ), —N((CH ₂ ) ₃ CH ₃ ) ₂ , —NH(CH ₂ CH(CH ₃ ) ₂ ), —N(CH ₂ CH(CH ₃ ) ₂ ) ₂ , —NH( (CH ₂ ) ₄ CH ₃ ), —N((CH ₂ ) ₄ CH ₃ ) ₂ , —NH((CH ₂ ) ₅ CH ₃ ), —N((CH ₂ ) ₅ CH ₃ ) ₂ and the like. but not limited to these. As used herein, "alkyl-substituted amino" is synonymous with "alkylamino".

"Protecting group" refers to a group of atoms that, when attached to a reactive functional group in a molecule, masks, reduces or prevents the reactivity of the functional group. The compounds of the present disclosure may be substituted with protecting groups as appropriate or necessary at any position such as any of R ₁ to R ₄ or substituents thereof or other substituents thereof, and the protecting groups are Compounds containing are also within the scope of this disclosure. Typically, protecting groups can be selectively removed during the synthetic process, if desired. Examples of protecting groups can be found in Greene and Wuts, Protective Groups in Organic Chemistry, 5th Edition, 2014, John Wiley & Sons, NY and Harrison et al., Compendium of Synthetic Organic Methods, vols. 1-8, John Wiley & Sons, NY etc. can be found. As used herein, a “protecting group” may fall under the definitions of 1)-53) for substituent α and 1)-26) for substituent β. In that case, in substituent group α1, "54) protecting group" is "protecting group other than 1) to 53)", and in substituent group β1, "27) protecting group" is "1) to 26). It may be described as "protecting group other than". Representative nitrogen protecting groups include formyl, acetyl, trifluoroacetyl, benzyl, benzyloxycarbonyl (“CBZ”), tert-butoxycarbonyl (“Boc”), trimethylsilyl (“TMS”), 2-trimethylsilylethanesulfonyl. (“TES”), trityl and substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl (“FMOC”), nitro-veratryloxycarbonyl (“NVOC”), and “Protect and the like, but are not limited thereto. Representative hydroxyl protecting groups are those in which the hydroxyl group is acylated (esterified) or alkylated, such as benzyl and trityl ethers, as well as alkyl ethers, tetrahydropyranyl ethers, trialkylsilyl ethers such as TMS, triethylsilyl, t-butyldimethylsilyl (TBDMS), triisopropylsilyl (TIPS)), alkyldiarylsilyl ethers (eg t-butyldiphenylsilyl (TBDPS)), triarylsilyl ethers (eg triphenylsilyl), glycol Ethers (eg, ethylene glycol ether, propylene glycol ether, etc.), and allyl ethers include, but are not limited to.

Amino groups possessed by the compounds of the present disclosure (e.g., amino groups possessed by the backbone, amino groups as substituents, amino groups in the substituents possessed by the compounds, etc.) are represented by a nitrogen protecting group or “Protect”. It may be protected by a group. The amino group in the substituents listed in the substituent group may be further protected with a nitrogen protecting group or a group represented by "Protect", and the protected substituent is used as a substituent. good too.

A hydroxy group possessed by the compound of the present disclosure (e.g., a hydroxy group as a substituent, a hydroxy group in the substituent possessed by the compound, a hydroxy group in the above substituent groups, etc.) is also protected with a hydroxy-protecting group. may A hydroxy group in a substituent listed in a substituent group may be further protected with a hydroxyl protecting group (such as a silyl ether) described herein, and the protected substituent may be may be used.

The compounds of the present disclosure are further described below.
Depending on the type of substituents, the compounds of the present disclosure may exist in stereoisomers such as tautomers, geometric isomers, and optical isomers, and the present disclosure includes them. That is, when one or more asymmetric carbon atoms are present in the compound of the present disclosure, diastereomers and optical isomers exist, and mixtures and isolated products of these diastereomers and optical isomers are also included in the compounds of the present disclosure.

This disclosure is also intended to include various hydrates, solvates and polymorphs.

Additionally, the compounds of the present disclosure contain isotopes such as ² H (or D), ³ H (or T), ¹¹ C ^{, 13} C, 14 C, ¹³ N, ¹⁵ N, ¹⁵ O, ³⁵ S, ¹⁸ F, ¹²⁵ I, etc.), and these compounds are also included in the compounds of the present disclosure.

Also included within the scope of this disclosure are prodrugs of the compounds of this disclosure. Prodrugs, in the present disclosure, refer to derivatives that are cleaved in vivo, eg, by acid hydrolysis or enzymatically, to give the compounds of Formula I or II described herein. For example, when the compound represented by Formula I or II described herein has a hydroxyl group, an amino group, or a carboxyl group, these groups can be modified according to conventional methods to produce prodrugs. The technology of prodrugs is described, for example, in C. G. Wermuth, "The Practice of Medicinal Chemistry", 4th Ed., Academic Press, (2015), Chapter 28.

For example, compounds having a carboxyl group include compounds in which the carboxyl group is an alkoxycarbonyl group, an alkylthiocarbonyl group, or an alkylaminocarbonyl group.

Further, for example, in the case of a compound having an amino group, a compound in which the amino group is substituted with an alkanoyl group to form an alkanoylamino group, a compound in which an alkoxycarbonyl group is substituted to form an alkoxycarbonylamino group, and an alkanoyloxymethylamino group. or hydroxylamine.

Further, for example, in the case of a compound having a hydroxyl group, the hydroxyl group is substituted with the alkanoyl group to form an alkanoyloxy group, a phosphoric acid ester compound, or an alkanoyloxymethyloxy group.

Examples of the alkyl moiety of these groups used for prodrug formation include the aforementioned alkyl groups, and the alkyl groups may be substituted, for example, with an alkoxy group or the like. Preferred examples include the following.

Examples of compounds in which the carboxyl group is an alkoxycarbonyl group include alkoxycarbonyl such as methoxycarbonyl or ethoxycarbonyl, or methoxymethoxycarbonyl, ethoxymethoxycarbonyl, 2-methoxyethoxycarbonyl, 2-methoxyethoxymethoxycarbonyl or Alkoxycarbonyl substituted with an alkoxy group such as valoyloxymethoxycarbonyl is included.

As used herein, "pharmaceutically acceptable salt" means acid addition salts and base addition salts that are acceptable for pharmaceutically use. Specific examples of "pharmaceutically acceptable salts" include acetate, propionate, butyrate, formate, trifluoroacetate, maleate, fumarate, tartrate, citrate, stearate salt, succinate, ethylsuccinate, malonate, lactobionate, gluconate, glucoheptonate, benzoate, methanesulfonate, benzenesulfonic acid, paratoluenesulfonate (tosylate), Lauryl sulfate, malate, ascorbate, mandelate, saccharinate, xinafoate, pamoate, cinnamate, adipate, cysteine, N-acetylcysteine, hydrochloride, bromide Acid addition salts such as hydrate, phosphate, sulfate, hydroiodide, nicotinate, oxalate, picrate, thiocyanate, undecanoate, acrylic acid polymer salt, carboxyvinyl polymer inorganic base addition salts such as lithium salts, sodium salts, potassium salts, calcium salts; organic base addition salts such as morpholine and piperidine; addition salts with amino acids such as aspartic acid and glutamic acid; but not limited to these. .

The phrase "a compound or an enantiomer thereof or a salt thereof or a solvate thereof" refers to a compound, an enantiomer of said compound, a salt of said compound, a salt of said enantiomer, a solvate of said compound, a solvate of said enantiomer , a solvate of a salt of said compound, or a solvate of a salt of said enantiomer.

As used herein, a therapeutic agent that "prevents" cancer, etc., reduces the occurrence of a disorder or condition in a subject compared to an untreated subject, or Refers to a compound that delays the onset or reduces the severity of one or more symptoms of cancer compared to the subject being treated.

As used herein, the term "treating" cancer or the like includes prophylactic and/or therapeutic treatment. The term "prophylactic or therapeutic" treatment is art-recognized and includes administration to an individual of one or more compounds or pharmaceutical compositions of the invention. Whereas treatment is prophylactic (i.e., protects an individual from developing an undesirable condition) when administered prior to clinical manifestation of an undesirable condition (e.g., a disease or other undesirable condition in an individual) , treatment is therapeutic (ie, intended to diminish, ameliorate, or stabilize an existing undesirable condition or its side effects) when administered after the discovery of the undesirable condition.

The term "prodrug" is intended to include compounds that are converted under physiological conditions to therapeutically active agents of the present disclosure (eg, compounds of Formula I or II). A common method for making prodrugs is to include one or more selected moieties that are hydrolyzed under physiological conditions to expose the desired molecule. In other embodiments, the prodrug is converted by the enzymatic activity of the individual. For example, esters or carbonates (eg, esters or carbonates of alcohols or carboxylic acids) are preferred prodrugs of this disclosure. In certain embodiments, some or all of the compounds of formula I or II in the formulations represented above are, for example, hydroxyls in the parent compound are provided as esters or carbonates or are present in the parent compound Corresponding suitable prodrugs can be substituted for the carboxylic acid provided as an ester.

Pharmaceutical Compositions The compositions and methods of the disclosure can be utilized to treat an individual in need thereof. In certain embodiments, the individual is a mammal, such as a human, or a non-human mammal. When administered to animals, such as humans, the composition or compound is preferably administered as a pharmaceutical composition, eg, comprising a compound of the disclosure and a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers are well known in the art and include aqueous solutions such as water or buffered saline, or other solvents or vehicles such as glycols, glycerol, oils such as olive oil, and the like. , or injectable organic esters. In a preferred embodiment, such pharmaceutical compositions are for administration to humans, particularly by invasive routes (i.e., routes such as injection or implantation that avoid transport or diffusion across the epithelial barrier). ), the aqueous solution is pyrogen-free or substantially pyrogen-free. Excipients can be selected, for example, to effect delayed release of the agent or to selectively target one or more cells, tissues or organs. Pharmaceutical compositions can be in unit dosage forms such as tablets, capsules (including sprinkle capsules and gelatin capsules), granules, lyophilized for reconstitution, powders, liquids, syrups, suppositories, Or it can be an injection or the like. The composition can also be present in transdermal delivery systems, such as skin patches. The composition can also be presented in a liquid formulation suitable for topical administration, such as eye drops.

A pharmaceutically acceptable carrier is a physiologically acceptable agent that acts, for example, to stabilize, increase solubility, or increase absorption of a compound, such as a compound of the present disclosure. can contain Such physiologically acceptable agents include, for example, carbohydrates such as glucose, sucrose or dextran, antioxidants such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins or other stabilizers or excipients. forms and the like. The selection of pharmaceutically acceptable carriers, including physiologically acceptable agents, depends, for example, on the route of administration of the composition. The preparation or pharmaceutical composition may be a self-emulsifying drug delivery system or a self-microemulsifying drug delivery system. Pharmaceutical compositions (preparations) can also be liposomes or other polymeric matrices, in which, for example, the compounds of the present disclosure can be incorporated. Liposomes, such as liposomes containing phospholipids or other lipids, are nontoxic, physiologically acceptable and metabolizable carriers that are relatively simple to make and administer.

The phrase "pharmaceutically acceptable" is hereby adopted to mean that, within the scope of sound medical judgment, neither excessive toxicity, irritation, allergic response, nor other problems, Refers to compounds, materials, compositions and/or dosage forms that are suitable for use in contact with human and animal tissue, without complications, with a reasonable benefit/benefit ratio.

The phrase "pharmaceutically acceptable carrier" as used herein means a pharmaceutically acceptable material, composition or vehicle such as a liquid or solid filler, diluent, excipient, solvent or encapsulating material. Each carrier must be "acceptable" in the sense of being compatible with the other ingredients of the formulation and not injurious to the patient. Some examples of materials that can serve as pharmaceutically acceptable carriers include: (1) sugars such as lactose, glucose and sucrose; (2) starches such as corn starch and (3) cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose and cellulose acetate; (4) powdered tragacanth; (5) malt; (6) gelatin; (7) talc; Excipients such as cocoa butter and suppository waxes; (9) Oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; (10) Glycols such as propylene glycol. (11) polyols such as glycerin, sorbitol, mannitol and polyethylene glycol; (12) esters such as ethyl oleate and ethyl laurate; (13) agar; (14) buffering agents such as magnesium hydroxide; (15) alginic acid; (16) pyrogen-free water; (17) isotonic saline; (18) Ringer's solution; (19) ethyl alcohol; 21) Other non-toxic compatible substances employed in pharmaceutical formulations.

Pharmaceutical compositions (preparations) can be administered, for example, orally (for example, tablets in aqueous or non-aqueous solutions or suspensions, tablets, capsules (including sprinkle capsules and gelatin capsules), boluses, powders, granules, pastes for application to the tongue); absorption through the oral mucosa (e.g. sublingual); anal, rectal or vaginal (e.g. pessaries, creams or foams); parenterally (including intramuscularly, intravenously, subcutaneously or intrathecally, e.g. as a sterile solution or suspension); nasally; intraperitoneally; subcutaneously; transdermally (e.g. any of several routes of administration, including as a patch applied to the skin); and topically (e.g., as a cream, ointment or spray applied to the skin, or as eye drops). can be administered to a subject by Compounds may also be formulated for inhalation. In certain embodiments, the compound may simply be dissolved or suspended in sterile water. Details of suitable routes of administration and compositions suitable therefor can be found, for example, in U.S. Pat. Nos. 5,358,970 and 4,172,896, and patents cited therein.

The formulations may conveniently be presented in unit dosage form and may be prepared by any of the methods well-known in the art of pharmacy. The amount of active ingredient that can be combined with the carrier materials to produce a single dosage form will vary depending on the individual undergoing treatment, the particular mode of administration. The amount of active ingredient that can be combined with the carrier materials to produce a single dosage form will generally be that amount of the compound that produces a therapeutic effect. Generally, out of 100 percent, this amount will be from about 1 percent to about 99 percent active ingredient, preferably from about 5 percent to about 70 percent active ingredient, and most preferably from about 10 percent to about 30 percent active ingredient. range from

Methods of preparing these formulations or compositions include the step of bringing into association an active compound such as a compound of this disclosure with the carrier and, optionally, one or more accessory ingredients. In general, the formulations are formed by uniformly and intimately bringing into association the compounds of the present disclosure with liquid carriers or finely divided solid carriers, or both, and then, if necessary, shaping the product. prepared.

Formulations of the present disclosure suitable for oral administration include capsules (including sprinkle capsules and gelatin capsules), cachets, pills, tablets, lozenges (flavored bases, usually sucrose and acacia or tragacanth). ), as lyophilized, powders, granules, or solutions or suspensions in aqueous or non-aqueous liquids, or as oil-in-water or water-in-oil liquid emulsions, or as elixirs or syrups. or as a pastel (using an inert base such as gelatin and glycerin, or sucrose and acacia) and/or as a mouthwash, each of which is an active ingredient of the present disclosure. Contains a predetermined amount of compound. A composition or compound may also be administered as a bolus, electuary or paste.

To prepare solid dosage forms for oral administration, such as capsules (including sprinkle capsules and gelatin capsules), tablets, pills, dragees, powders, and granules, the active ingredient is combined in one or more mixed with multiple pharmaceutically acceptable carriers such as sodium citrate or dicalcium phosphate and/or any of the following: (1) fillers or bulking agents such as starch, lactose, sucrose, glucose , mannitol, and/or silicic acid; (2) binders such as carboxymethylcellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose and/or acacia; (3) humectants such as glycerol; (4) disintegration (5) dissolution retardants such as paraffin; (6) absorption enhancers such as quaternary (7) Wetting agents such as cetyl alcohol and glycerol monostearate; (8) Absorbents such as kaolin and bentonite clay; (9) Lubricants such as talc, calcium stearate, stearin. (10) complexing agents such as modified and unmodified cyclodextrins; and (11) colorants. In the case of capsules (including sprinkle capsules and gelatin capsules), tablets and pills, the pharmaceutical composition may also contain buffering agents. Solid compositions of a similar type can also be employed as fillers in soft and hard-filled gelatin capsules, using excipients such as lactose or milk sugar, and high molecular weight polyethylene glycols and the like.

A tablet may be made by compression or molding, optionally with one or more accessory ingredients. Compressed tablets may contain binders such as gelatin or hydroxypropylmethylcellulose, lubricants, inert diluents, preservatives, disintegrants such as sodium starch glycolate or cross-linked sodium carboxymethylcellulose, surfactants or dispersing agents. can be prepared using Molded tablets may be made by molding in a suitable machine a mixture of the powdered compound moistened with an inert liquid diluent.

Tablets and other solid dosage forms of pharmaceutical compositions, such as dragees, capsules (including sprinkle capsules and gelatin capsules), pills and granules, etc., may optionally be scored or coated and Shells may be prepared with, for example, enteric coatings and other coatings well known in the pharmaceutical formulating art. They also employ, for example, hydroxypropylmethylcellulose, other polymeric matrices, liposomes and/or microspheres in different proportions to provide a desired release profile, such as sustained release or controlled release of active ingredients therein. It may be formulated to provide release. These may be obtained, for example, by filtration through a bacteria-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved in sterile water, or some other sterile injectable medium immediately prior to use. It may be sterilized. These compositions may also optionally contain emulsifying agents to direct the active ingredient(s) only or preferentially in certain parts of the gastrointestinal tract, optionally It may be a composition that releases in a delayed fashion. Examples of embedding compositions that can be used include polymeric substances and waxes. The active ingredient can also be in micro-encapsulated form, where appropriate, with one or more of the excipients noted above.

Liquid dosage forms useful for oral administration include pharmaceutically acceptable emulsions, lyophilized for reconstitution, microemulsions, solutions, suspensions, syrups and elixirs. In addition to the active ingredient, the liquid dosage form may contain inert diluents commonly used in the art, such as water or other solvents, cyclodextrin and its derivatives, solubilizers and emulsifiers, such as ethyl alcohol. , isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, oils (especially cottonseed, peanut, corn, germ, olive, castor and sesame), Glycerol, tetrahydrofuryl alcohol, polyethylene glycol and fatty acid esters of sorbitan, and the like, mixtures thereof, and the like may also be included.

Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, coloring, perfuming and preserving agents.

Suspending agents, in addition to the active compound, contain suspending agents such as ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar and tragacanth, and these may contain a mixture of

Formulations of pharmaceutical compositions for rectal, vaginal, or urethral administration may be presented as suppositories, which contain one or more active compounds such as cocoa butter, polyethylene glycol, It can be prepared by mixing with one or more suitable nonirritating excipients or carriers, including suppository waxes or salicylates, which are solid at room temperature but liquid at body temperature. Yes, and thus melt in the rectal or vaginal cavity to release the active compound.

Formulations of the pharmaceutical composition for oral administration may be presented as a mouthwash, or oral spray, or oral ointment.

Alternatively or additionally, compositions may be formulated for delivery via a catheter, stent, wire, or other intraluminal device. Delivery via such devices may be particularly useful for bladder, urethral, ureteral, rectal, or intestinal delivery.

Formulations suitable for vaginal administration also include pessaries, tampons, creams, gels, pastes, foams or spray formulations containing such carriers as are known in the art to be suitable. include.

Dosage forms for topical or transdermal administration include powders, sprays, ointments, pastes, creams, lotions, gels, solutions, patches and inhalants. The active compound may be mixed under sterile conditions with a pharmaceutically acceptable carrier, and with any preservatives, buffers, or propellants that may be required.

Ointments, pastes, creams and gels contain, in addition to the active compound, excipients such as animal and vegetable oils, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite. , silicic acid, talc and zinc oxide, or mixtures thereof.

Powders and sprays can contain, in addition to the active compound, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons and volatile unsubstituted hydrocarbons, such as butane and propane.

Transdermal patches have the added advantage of providing controlled delivery of a compound of the present disclosure to the body. Such dosage forms can be made by dissolving or dispersing the active compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate of such flux can be controlled either by providing a rate controlling membrane or by dispersing the compound within a polymer matrix or gel.

Ophthalmic formulations, eye ointments, powders, solutions, and the like are also contemplated as being within the scope of this disclosure. Exemplary ophthalmic formulations include U.S. Patent Application Publication Nos. 2005/0080056, 2005/0059744, 2005/0031697 and 2005/004074 and U.S. Patent No. 6,583,124 (these the contents of which are incorporated herein by reference). If desired, the liquid ophthalmic formulation has properties similar to or is compatible with tears, aqueous humor or vitreous humor. A preferred route of administration is local administration (eg, topical administration, such as eye drops, or administration via an implant).

The phrases "parenteral administration" and "administered parenterally" as used herein mean modes of administration other than enteral and topical administration, usually by injection, without limitation. , intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subepidermal, intraarticular, subcapsular, subarachnoid, intraspinal and intrasternal Injections and infusions are included. Pharmaceutical compositions suitable for parenteral administration comprise one or more active compounds in one or more pharmaceutically acceptable sterile, isotonic, aqueous or non-aqueous solutions, dispersions liquids, suspensions or emulsions, or in combination with sterile powders that can be reconstituted into sterile injectable solutions or dispersions immediately prior to use, which contain antioxidants, buffers, bacteriostats, and the intended recipe. Solutes that render the formulation isotonic with the blood of the ent, or suspending or thickening agents may be included.

Examples of suitable aqueous and non-aqueous carriers that can be employed in pharmaceutical compositions of the present disclosure include water, ethanol, polyols such as glycerol, propylene glycol and polyethylene glycol, and suitable mixtures thereof, vegetable oils, Examples include olive oil and the like, and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by using coating materials such as lecithin, by maintaining the required particle size in the case of dispersions, and by using surfactants. can.

These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. Prevention of the action of microorganisms can be ensured by the inclusion of various antibacterial and antifungal agents such as parabens, chlorobutanol, and phenolsorbic acid. It may also be desirable to include isotonic agents, such as sugars and sodium chloride, into the compositions. Additionally, prolonged absorption of the injectable pharmaceutical form can be caused by the inclusion of agents that delay absorption, such as aluminum monostearate and gelatin.

In some cases, it is desirable to slow the absorption of drugs from subcutaneous or intramuscular injections in order to prolong the drug's effect. This may be accomplished by the use of a liquid suspension of crystalline or amorphous material with poor water solubility. Thus, the absorption rate of a drug depends on its dissolution rate, which in turn can depend on crystal size and crystal form. Alternatively, delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.

Injectable depot forms are made by forming microencapsule matrices of the subject compounds in biodegradable polymers such as polylactide-polyglycolide. Depending on the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues.

For use in the methods of the present disclosure, the active compound may be provided per se or, for example, from 0.1 to 99.5% (more preferably from 0.5 to 90%) of active ingredient, It may be provided as a pharmaceutical composition containing in combination with a pharmaceutically acceptable carrier.

Methods of introduction can also be provided by rechargeable or biodegradable devices. In recent years, various sustained release polymeric devices have been developed and tested in vivo for the controlled delivery of drugs, including proteinaceous biologics. By using a variety of biocompatible polymers, including hydrogels, including both biodegradable and non-degradable polymers, implants for sustained release of compounds at specific target sites have been developed. can be formed.

By varying the actual dosage level of the active ingredient in the pharmaceutical composition, the therapeutic response desired for the particular patient, composition and mode of administration without being toxic to that particular patient. An amount of active ingredient effective to achieve the

The dosage level selected will depend on the activity of the particular compound or combination of compounds employed, or esters, salts or amides thereof, the route of administration, the time of administration, the excretion rate of the particular compound(s) employed. , duration of treatment, other drugs, compounds and/or substances used in combination with the particular compound(s) employed, age, sex, weight, condition of the patient undergoing treatment, general It depends on a variety of factors, including general health and previous medical history, as well as similar factors well known in the medical arts.

A physician or veterinarian having ordinary skill in the art can readily determine and prescribe the therapeutically effective amount of the pharmaceutical composition required. For example, a physician or veterinarian may begin dosage of a pharmaceutical composition or compound at a level below that required to achieve the desired therapeutic effect and increase the dosage until the desired effect is achieved. It can be increased gradually. By "therapeutically effective amount" is meant a concentration of the compound sufficient to produce the desired therapeutic effect. It is generally understood that the effective amount of compound will vary according to the subject's weight, sex, age, and medical history. Other factors influencing effective dosage include, but are not limited to, the severity of the patient's condition, the disorder being treated, the stability of the compound, and, if desired, the number of doses administered with the compound of this disclosure. Another type of therapeutic agent can be mentioned. A higher total dose can be delivered by multiple administrations of the agent. Methods of determining efficacy and dosage are known to those of skill in the art (Isselbacher et al. (1996) Harrison's Principles of Internal Medicine, 13th Edition, pp. 1814-1882, incorporated herein by reference).

In general, a suitable daily dose of an active compound for use in the compositions and methods of the disclosure will be that amount of the compound which is the lowest dose effective to produce a therapeutic effect. Such effective doses generally depend on the factors described above.

If desired, the effective daily dose of the active compound can be 1, 2, 3, 4, 5, or 6 or 6 doses administered separately at appropriate intervals throughout the day, optionally in unit dosage form. It may also be administered as more than one divided dose. In certain embodiments of the disclosure, the active compound may be administered two or three times daily. In preferred embodiments, the active compound is administered once daily.

Patients receiving this treatment are any animal in need of treatment, including primates, particularly humans, and other mammals such as horses, cows, pigs, and sheep; and poultry and pets in general. .

In certain embodiments, the compounds of the disclosure may be used alone or co-administered with another type of therapeutic agent. As used herein, the phrase "co-administered" is such that a second compound is administered while the previously administered therapeutic compound is still active in the body (e.g., the two The compounds are effective simultaneously in the patient's body, which may include a synergistic effect of the two compounds), refers to any mode of administration of two or more than two different therapeutic compounds. For example, different therapeutic compounds can be administered either simultaneously or sequentially, either in the same formulation or in separate formulations. In certain embodiments, the different therapeutic compounds can be administered within 1 hour, 12 hours, 24 hours, 36 hours, 48 hours, 72 hours, or 1 week of each other. Individuals undergoing such treatment may therefore benefit from the combined effects of different therapeutic compounds.

In certain embodiments, co-administration of a compound of the present disclosure with one or more additional therapeutic agent(s) (e.g., one or more additional chemotherapeutic agent(s)) is , provide improved efficacy compared to each individual administration of a compound of the disclosure (e.g., a compound of Formula I or Formula II) or one or more additional therapeutic agent(s). In certain such embodiments, co-administration provides an additive effect, where additive effect is the individual administration of the compound of the disclosure and the one or more additional therapeutic agent(s). refers to the respective sum of the effects of administration of

In one embodiment, the compounds of the present disclosure can be administered orally or parenterally, either directly or using an appropriate dosage form and formulated into a formulation, medicament or pharmaceutical composition. Specific examples of these dosage forms include, but are not limited to, tablets, capsules, powders, granules, solutions, suspensions, injections, patches, poultices and the like. In addition, these formulations can be produced by known methods using additives that are commonly used as pharmaceutical additives.

These additives include excipients, disintegrants, binders, fluidizers, lubricants, coating agents, solubilizers, solubilizers, thickeners, dispersants, and stabilizers, depending on the purpose. , sweeteners, flavors and the like can be used. Specific examples of these additives include lactose, mannitol, crystalline cellulose, low-substituted hydroxypropylcellulose, corn starch, partially pregelatinized starch, carmellose calcium, croscarmellose sodium, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl Alcohol, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, propylene glycol, titanium oxide, talc, and the like, but are not limited to these.

The dosage of the compound of the present disclosure is appropriately selected depending on the subject to be administered, the route of administration, the target disease, disorder or symptom, the age or body weight of the subject, a combination thereof, and the like. For example, in the case of oral administration, the lower limit is 0.01 mg (preferably 100 mg) and the upper limit is 10000 mg (preferably 6000 mg) per day for adults, and this amount is administered once or several times a day. Can be administered separately.

Compounds, etc. of the present disclosure may be provided as a kit. As used herein, the term "kit" generally refers to parts to be provided divided into two or more compartments (e.g., compounds, test agents, diagnostic agents, therapeutic agents, antibodies, labels, instructions, etc.). unit. When it is preferable to administer a specific drug (such as a compound) only to an appropriate patient after identifying a patient to be administered once by a reagent for defining patient characteristics, such as a companion diagnostic agent, A kit may be provided when a diagnostic agent and a therapeutic agent are provided in combination. Alternatively, when the purpose is to provide a composition that should not be provided in a mixed form for the sake of stability, such as a specific unstable drug, and should preferably be used in a mixed form immediately before use. Additionally, this kit format is preferred. Such kits preferably include portions provided (e.g., instructions describing how to use compounds, test agents, diagnostic agents, therapeutic agents, or how reagents should be handled, or Advantageously, when the kit is used as a reagent kit herein, the kit usually includes instructions describing how to use the test agent, diagnostic agent, therapeutic agent, antibody, etc. This includes books, etc.

As used herein, the term "active ingredient" refers to a component contained in an amount necessary to obtain the desired effect of the composition of the present disclosure, such as treatment, prevention, or inhibition of progression, and the effect is below the desired level. Other ingredients may also be included as long as they are not compromised. In addition, the medicaments, compositions, etc. of the present disclosure may be formulated. In addition, the administration route of the medicament, composition, etc. of the present disclosure may be either oral or parenteral, and can be appropriately set according to the form of the preparation.

As used herein, "instructions" (including package inserts and labels used by the US FDA) are instructions to a physician or other user on how to use the present disclosure. The instructions describe the detection method of the present disclosure, how to use the diagnostic agent, or instructions for administering medicine or the like. In addition, the instructions may include a statement instructing oral or local administration (for example, by injection) as the site of administration. This instruction is prepared in accordance with the format prescribed by the regulatory authority of the country in which this disclosure is implemented (for example, the Ministry of Health, Labor and Welfare in Japan, the Food and Drug Administration (FDA) in the United States, etc.) and is approved by the regulatory authority It is stated that it has received The instructions are so-called package inserts and labels, and are usually provided in paper media, but are not limited to them. ) can also be provided in a form such as

In one embodiment, the compounds of the present disclosure are compounds with anticancer activity against cancer. Said cancer includes leukemia.

The timing of administration of the compounds of the present disclosure and their therapeutic agents is not limited, and they may be administered simultaneously or at different times to the subject to whom they are administered. Combinations of the compounds of the present disclosure and their therapeutic agents may also be used. The dosage of these therapeutic agents can be appropriately selected based on the clinically used dosage. In addition, the compounding ratio of the compounds of the present disclosure and their therapeutic agents can be appropriately selected depending on the subject to be administered, the administration route, the target disease, disorder or symptom, the age or weight of the subject, or a combination thereof. can be done.

In one embodiment of the present disclosure, compounds of the present disclosure can be administered in combination, either simultaneously or at different times, in using the pharmaceutical composition. Such pharmaceutical compositions are also within the scope of this disclosure.

Such medicaments, formulations, pharmaceutical compositions may be prepared using any technique known in the art to prepare compounds of the present disclosure and/or additional agents (e.g., antibacterial agents, antiviral agents (e.g., ribavirin, amantadine, etc.)). ), sedatives (e.g., ketamine, midazolam, etc.), together or separately, as a combination drug or as a separate drug, by mixing with any suitable ingredients, Any known technique can be used to formulate appropriate formulations such as tablets, capsules, powders, granules, liquids, suspensions, injections, patches, and poultices. When the compounds of the present disclosure and/or additional agents (e.g., antibacterial agents, antiviral agents (e.g., ribavirin, amantadine, etc.), sedatives (e.g., ketamine, midazolam, etc.), etc.) are prepared as separate agents , may be provided as a kit of two agents, provided as a single agent of one component and the other component (in the case of compounds of the present disclosure, an additional agent; In the case of antiviral agents (e.g., ribavirin, amantadine, etc.), sedatives (e.g., ketamine, midazolam, etc.), which are compounds of the present disclosure) are administered in combination at the same time or at the same time. It may be provided with a document (package insert, etc.).

When the compounds of the present disclosure are used as an active ingredient in a medicament, it is not intended for use in humans only, but other non-human animals (cats, dogs, cows, horses, bats, foxes, mongooses, raccoons). etc.) can also be used.

(Preventive or therapeutic method)
The present disclosure also provides a method of preventing or treating cancer comprising administering to a subject in need thereof a compound of Formula I or Formula II or a pharmaceutically acceptable salt thereof or a solvate thereof. A method is provided comprising administering the product, or a pharmaceutical composition comprising the same. In one embodiment, the method of preventing or treating cancer comprises administering to a subject in need thereof a therapeutically effective amount of a compound of Formula I or Formula II, or a pharmaceutically acceptable salt thereof, or or a pharmaceutical composition comprising the same.

(Prophylactic or therapeutic use)
In one embodiment of the present disclosure, the use of a compound of formula I or formula II or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for preventing or treating cancer offer.

The disclosure also provides a compound of Formula I or Formula II or a pharmaceutically acceptable salt or solvate thereof for use in the prevention or treatment of cancer.

(Method for producing compounds of the present disclosure)
Methods for producing the compounds of the present disclosure are described below by way of examples, but the present disclosure is by no means limited to these.

The compounds of the present disclosure can be produced, for example, but not limited to, by the production methods described below. These production methods can be appropriately improved based on the knowledge of those skilled in organic synthetic chemistry. In the production method described below, the compounds used as starting materials may be salts thereof as long as they do not interfere with the reaction.

In the following production methods, even if the use of a protecting group is not specifically specified, if any functional group other than the reaction site changes under the reaction conditions, or if it is inappropriate to carry out post-reaction treatments In some cases, the desired compound can be obtained by protecting the site other than the reaction site as necessary and deprotecting after the reaction is completed or after a series of reactions. Protective groups used in these processes are described in literature (Peter G. M. Wuts, “Greene's Protective Groups in Organic Synthesis”, 5th Ed., John Wiley & Sons, Inc., Hoboken, New Jersey (2014)), etc. Any conventional protecting group can be used. In addition, introduction and removal of a protecting group can be carried out by a method commonly used in organic synthetic chemistry (eg, the methods described in the above literature) or a method analogous thereto.

The starting materials and intermediates in the following production methods can be purchased as commercial products, or can be obtained by synthesizing from known compounds according to methods described in known literature or known methods. Moreover, these starting materials and intermediates may be salts thereof as long as they do not interfere with the reaction.

Intermediates and target compounds in the production methods below can also be converted into other compounds included in the present disclosure by appropriately converting their functional groups. The transformation of the functional group at that time is performed by a method commonly used in synthetic organic chemistry (for example, described in RC Larock, "Comprehensive Organic Transformations", ^2nd Ed., John Wiley and Sons, Inc., New York (1999). method, etc.) or a method based on them.

The inert solvent in the following production method means a solvent that does not react with raw materials, reagents, bases, acids, catalysts, ligands, etc. used in the reaction (hereinafter sometimes referred to as "raw materials used in the reaction, etc."). means. In addition, even if the solvent used in each step reacts with the raw materials used in the reaction, it can be used as an inert solvent as long as the desired reaction proceeds to obtain the desired compound.

式中、Ｒ_３は本明細書に定義される通りである。 (manufacturing scheme)
Synthetic scheme 1
Production of Intermediate 1 Intermediate 1 can be produced in one pot from the following four components according to a known method (eg, the method described in J.Org.Chem. 2014, 1207-1214).

wherein _R3 is as defined herein.

式中、Ｒ_３は本明細書に定義される通りである。 Synthetic scheme 2
Preparation of Intermediate 2 Intermediate 2 can be prepared by subjecting Intermediate 1 to hydrolysis conditions.

wherein _R3 is as defined herein.

式中、Ｒ_２、Ｒ_３は本明細書に定義される通りである。
中間体３は、下記化合物を用いて中間体１と同様の方法によっても製造できる。

式中、Ｒ_２、Ｒ_３は本明細書に定義される通りである。 Synthetic scheme 3
Preparation of Intermediate 3 Intermediate 3 can be prepared by condensation reaction of Intermediate 2 and Compound 7.

wherein R ₂ and R ₃ are as defined herein.
Intermediate 3 can also be prepared by a method similar to Intermediate 1 using the following compounds.

wherein R ₂ and R ₃ are as defined herein.

式中、Ｒ_２、Ｒ_３は本明細書に定義される通りである。 Synthetic scheme 4
Preparation of Intermediate 4 Intermediate 4 can be prepared by removing the 2-nitrobenzenesulfonyl group (Ns group) of Intermediate 3.

wherein R ₂ and R ₃ are as defined herein.

式中、Ｒ_２、Ｒ_３は本明細書に定義される通りである。 Synthetic scheme 5
Preparation of Intermediate 5 Intermediate 5 can be prepared from Intermediate 4 by reduction, for example as follows.

wherein R ₂ and R ₃ are as defined herein.

式中、Ｒ_１、Ｒ_２、及びＲ_３は本明細書に定義される通りである。
化合物１は、化合物２を還元することにより製造することもできる。

式中、Ｒ_１、Ｒ_２、及びＲ_３は本明細書に定義される通りである。 Synthetic scheme 6
Production of compound 1 or compound 2 Compound 1 or compound 2 can be produced by modifying intermediate 5 or intermediate 4 by, for example, amidation or alkylation reaction.

wherein R ₁ , R ₂ and R ₃ are as defined herein.
Compound 1 can also be prepared by reducing compound 2.

wherein R ₁ , R ₂ and R ₃ are as defined herein.

The intermediates and target compounds in the above production method can be purified by purification methods commonly used in synthetic organic chemistry (e.g., neutralization, filtration, extraction, washing, drying, concentration, recrystallization, various chromatography, etc.). It can be isolated and purified. Further, each intermediate can be subjected to the next reaction without particular purification.

An optically active form of the compound of the present disclosure can be produced by using an optically active starting material or intermediate, or by optically resolving the intermediate or final racemate. Examples of the optical resolution method include, but are not limited to, a separation method using an optically active column, a separation method such as a fractional crystallization method, and the like. Diastereomers of the compounds of the present disclosure can be prepared by separation methods such as, but not limited to, column chromatography and fractional crystallization.

Pharmaceutically acceptable salts of compounds represented by Formula I or II are compounds of Formula I or It can be produced by mixing a compound represented by II with a pharmaceutically acceptable acid or base.

(preferred embodiment)
Preferred embodiments of the present disclosure are described below. The embodiments provided below are provided for a better understanding of the disclosure, and it is understood that the scope of the disclosure should not be limited to the following description. Therefore, it is clear that a person skilled in the art can make appropriate modifications within the scope of the present disclosure in light of the description in this specification. It is also understood that the following embodiments of the disclosure can be used singly or in combination.

により表される化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物として例示することができる。式Ｉ中、
Ｒ_１は、必要に応じて置換されたアルキル、必要に応じて置換されたアルケニル、必要に応じて置換されたアルキニル、必要に応じて置換されたシクロアルキル、必要に応じて置換されたヘテロシクロアルキル、必要に応じて置換されたアリール、必要に応じて置換されたヘテロアリール、または必要に応じて置換されたカルボニルであり、Ｒ_２およびＲ_３は各々独立して、水素、必要に応じて置換されたアルキル、必要に応じて置換されたシクロアルキル、必要に応じて置換されたヘテロシクロアルキル、必要に応じて置換されたアリール、または必要に応じて置換されたヘテロアリールである。 In one aspect, the compounds of the present disclosure have Formula I:

can be exemplified as a compound represented by or an enantiomer thereof, a salt thereof, or a solvate thereof. In Formula I,
R ₁ is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocyclo alkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted carbonyl, where R ₂ and R ₃ are each independently hydrogen, optionally It is substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl.

により表される化合物もしくはそのエナンチオマーまたはそれらの塩またはそれらの溶媒和物として例示することができる。式ＩＩ中、
Ｒ_１は、必要に応じて置換されたアルキル、必要に応じて置換されたアルケニル、必要に応じて置換されたアルキニル、必要に応じて置換されたシクロアルキル、必要に応じて置換されたヘテロシクロアルキル、必要に応じて置換されたアリール、必要に応じて置換されたヘテロアリール、または必要に応じて置換されたカルボニルであり、Ｒ_２およびＲ_３は各々独立して、水素、必要に応じて置換されたアルキル、必要に応じて置換されたシクロアルキル、必要に応じて置換されたヘテロシクロアルキル、必要に応じて置換されたアリール、または必要に応じて置換されたヘテロアリールである。 In one aspect, the compounds of the present disclosure have formula II:

can be exemplified as a compound represented by or an enantiomer thereof, a salt thereof, or a solvate thereof. In formula II,
R ₁ is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocyclo alkyl, optionally substituted aryl, optionally substituted heteroaryl, or optionally substituted carbonyl, where R ₂ and R ₃ are each independently hydrogen, optionally It is substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted heteroaryl.

In one embodiment, R ₁ is optionally substituted alkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted arylalkyl , optionally substituted heteroarylalkyl, optionally substituted carboxyalkyl, optionally substituted carbamoylalkyl, optionally substituted aminoalkyl, optionally substituted alkenyl , optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbonyl, optionally substituted alkylcarbonyl, optionally substituted alkenylcarbonyl, optionally substituted cycloalkylcarbonyl, optionally substituted arylcarbonyl, optionally substituted carboxy, or optionally substituted carbamoyl, and R ₂ and R ₃ are each independently optionally substituted alkyl, optionally substituted cycloalkyl alkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted carbonylalkyl, optionally substituted carboxyalkyl, optionally substituted carbamoylalkyl, optionally substituted aminoalkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, or optionally substituted is heteroaryl.

In one embodiment, R ₁ is C _1-6 alkyl, C _3-10 cycloalkylC _1-6 alkyl,
C _3-10 heterocycloalkylC _1-6 alkyl, C _3-10 heterocycloalkyl C _1-6 alkyl substituted with C _1-6 alkyl, C _3-10 heterocyclo substituted with tert-butoxycarbonyl group AlkylC _1-6 alkyl, C _3-10 arylC _1-6 alkyl, C _3-10 arylC _1-6 alkyl substituted with C _1-6 alkyl, C _3-10 arylC ₁ substituted with halogen _-6 alkyl, C _3-10 arylC _1-6 alkyl substituted with hydroxy, C _3-10 arylC _1-6 alkyl substituted with C _1-6 alkoxy, C _3-10 heteroarylC _1-6 Alkyl, C _3-10 heteroaryl C _1-6 alkyl substituted by tert-butoxycarbonyl group, carboxy C _1-6 alkyl, carboxy C _1-6 alkyl substituted by C _1-6 alkyl, carbamoyl C _{1- 6} alkyl, amino C _1-6 alkyl, amino C _1-6 alkyl substituted with C _1-6 alkyl, C _2-6 alkenyl, C _2-6 alkynyl, C _3-10 cycloalkyl, C _3-10 hetero cycloalkyl, C _3-10 aryl, C _3-10 aryl substituted with halogen, C _3-10 heteroaryl, carbonyl substituted with C _3-10 cycloalkyl, carbonyl substituted with C _2-6 alkenyl, carbonyl substituted with C _3-10 aryl, C _1-6 alkylcarbonyl,
C _1-6 alkylcarbonyl substituted by halogen, C _1-6 alkylcarbonyl substituted by hydroxy, C _1-6 alkylcarbonyl substituted by C _1-6 alkoxy, C _3-10 cycloalkyl substituted C _1-6 alkylcarbonyl, C _1-6 alkylcarbonyl substituted with C _3-10 heteroaryl, C _1-6 alkylcarbonyl substituted with carboxy, C _1-6 substituted with C _1-6 alkylcarboxy alkylcarbonyl, C _1-6 alkylcarbonyl substituted with carbamoyl, C _1-6 alkylcarbonyl substituted with amino, C _1-6 alkylcarbonyl substituted with tert-butoxycarbonylamino, C ₁ substituted with guanidino _-6 alkylcarbonyl, C _3-10 aryl C _1-6 alkylcarbonyl,
C _3-10 arylC _1-6 alkylcarbonyl substituted with halogen, C _3-10 arylC _1-6 alkylcarbonyl substituted with hydroxy, C _3-10 arylC ₁ substituted with C _1-6 alkoxy _-6 alkylcarbonyl, C _1-6 alkyl substituted carboxy, C _3-10 arylC _1-6 alkyl substituted carboxy, C _1-6 alkyl substituted carbamoyl, C _3-10 aryl C _{1 -6} alkyl-substituted carbamoyl, C _3-10 cycloalkyl-substituted carbamoyl, and C _3-10 aryl-substituted carbamoyl.

In one embodiment, R ₁ is C _1-6 alkyl, hydroxy-substituted C _1-4 alkyl, carbamoyl-substituted C _1-4 alkyl, amino-substituted C _1-6 alkyl, guanidino-substituted C _1-4 alkyl, carboxy substituted C _1-4 alkyl, C _1-4 alkoxycarbonyl substituted C _1-4 alkyl, C _6-10 aryl C _1-4 alkyl, hydroxy substituted C _6-10 aryl C _1-4 alkyl, C _1-4 alkoxy-substituted C _6-10 arylC _1-4 alkyl, halo-substituted C _6-10 arylC _1-4 alkyl, or C _5-6 cycloalkylC _{1- 4} alkyl.

In one embodiment, R ₂ is
C _1-6 alkyl,
C _1-6 alkyl substituted with C 3-10 cycloalkyl, C _1-6 alkyl substituted _with C _3-10 heteroaryl, C _1-6 alkyl substituted with pyrrolidinecarbonyl, C substituted with guanidino _1-6 alkyl, C _1-6 alkyl substituted by hydroxy, C _1-6 alkyl substituted by C _1-6 alkoxy, C _3-10 arylC _1-6 alkyl, C _3- substituted by halogen ₁₀ arylC _1-6 alkyl, C _3-10 arylC _1-6 alkyl substituted by hydroxy, C _3-10 arylC _{1-6 alkyl substituted by C 1-6 alkoxy} , carboxyC _1-6 alkyl , carboxy C _1-6 alkyl substituted with C _1-6 alkyl, carbamoyl C _1-6 alkyl, carbamoyl C _1-6 alkyl substituted with C _1-6 alkyl, amino C _1-6 alkyl, C _1- aminoC _1-6alkyl substituted by _6alkyl and aminoC _1-6alkyl substituted by tert-butoxycarbonyl, C _3-10 cycloalkyl, C _3-10 heterocycloalkylC _3-10 aryl, halogen substituted C _3-10 aryl, or C _3-10 heteroaryl;

In _one embodiment, R ₃ is C _1-6 alkyl, C _{1-6 alkyl substituted with C 3-10} cycloalkyl, C _1-6 alkyl substituted with C _3-10 heteroaryl, substituted with guanidino C _1-6 alkyl substituted with hydroxy, C _1-6 alkyl substituted with hydroxy, C _1-6 alkyl substituted with C _1-6 alkoxy, C _3-10 arylC _1-6 alkyl substituted with halogen C _3-10 arylC _1-6 alkyl, C _3-10 arylC _1-6 alkyl substituted _{by hydroxy, C 3-10 arylC 1-6 alkyl substituted by C 1-6 alkoxy ,} carboxyC _{1 -6} alkyl, carboxyC _1-6 alkyl substituted with C _1-6 alkyl, carbamoyl C _1-6 alkyl, carbamoyl C _1-6 alkyl substituted with C _1-6 alkyl, amino C _1-6 alkyl, aminoC _1-6 alkyl substituted with C _1-6 alkyl, amino C _1-6 alkyl substituted with tert-butoxycarbonyl, C _3-10 cycloalkyl, C _3-10 heterocycloalkyl, C _3-10 aryl, or C _3-10 aryl substituted with halogen.

In one embodiment, R ₁ is a group selected from the table below.

In one embodiment, _R2 is a group selected from the table below.

In one embodiment, _R3 is a group selected from the table below.

(medicine)
In one aspect, the present disclosure provides medicaments (compositions) for treating, preventing or managing diseases, disorders or symptoms caused by cancer. Such medicaments or pharmaceutical compositions can be used in the preparation of individual single unit dosage forms. Pharmaceutical compositions and dosage forms of this disclosure contain a compound of this disclosure or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, and optionally an additional active agent. Pharmaceutical compositions and dosage forms of this disclosure can further contain one or more carriers, excipients or diluents.

Pharmaceutical compositions and dosage forms of the disclosure can also contain one or more additional active agents or ingredients. Consequently, pharmaceutical compositions and dosage forms of this disclosure may contain a compound of this disclosure, or a pharmaceutically acceptable salt, solvate or stereoisomer thereof, and at least one second active agent. Examples of optional second active agents are disclosed herein.

Cancers that the present disclosure may target include leukemia.

In one embodiment, the compounds of the present disclosure are administered orally or parenterally (e.g., transmucosally (e.g., sublingually, nasally, vaginally, intracystic, rectal, transpreputial, intraocular, intrabuccal or ear), parenterally (e.g. subcutaneous, intravenous, bolus injection, intramuscular or intraarterial), topical (e.g. eye drops or other ophthalmic preparations), transdermal or transepidermal), directly Alternatively, it can be formulated into a formulation, medicament or pharmaceutical composition using an appropriate dosage form and administered. Specific examples of these dosage forms include tablets, caplets, capsules such as elastic soft gelatin capsules, cachets, troches, powders, lozenges, granules, liquids, dispersants, suppositories, and aerosols. (e.g. nasal spray or inhalant), gels, suspensions (e.g. aqueous or non-aqueous liquid suspensions, oil-in-water liquid emulsions or water-in-oil liquid emulsions), elixirs, injections, Examples include, but are not limited to, patches, poultices, and the like. In addition, these formulations can be produced by known methods using additives that are commonly used as pharmaceutical additives. The present disclosure also provides liquid dosage forms suitable for oral or transmucosal administration to a patient, including elixirs, liquid dosage forms suitable for parenteral administration to a patient, eye drops or other topical administration. Ophthalmic preparations; and sterile solids (e.g., crystalline or amorphous solids), etc., which can be reconstituted to provide liquid dosage forms suitable for parenteral administration to patients. There may be. The present disclosure can be administered as a single unit dosage form.

Additives that can be used in the present disclosure include excipients, disintegrants, binders, fluidizers, lubricants, coating agents, solubilizers, solubilizers, thickeners, and dispersants, depending on the purpose. , stabilizers, sweeteners, flavors and the like can be used. Specific examples of these additives include lactose, mannitol, crystalline cellulose, low-substituted hydroxypropylcellulose, corn starch, partially pregelatinized starch, carmellose calcium, croscarmellose sodium, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl Alcohol, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, propylene glycol, titanium oxide, talc, and the like, but are not limited to these.

The composition, shape and type of compositions and dosage forms of the disclosure will typically vary depending on their use. For example, a dosage form used for the acute treatment of a disease, disorder or condition may contain large amounts of one or more active ingredients, which is not the same as a dosage form used in the chronic treatment of the disease, disorder or condition. contains more than Similarly, parenteral dosage forms may contain lower amounts of one or more active ingredients, and contain less of the active ingredient than oral dosage forms used in the treatment of the disease, disorder, or condition. These and other ways in which specific dosage forms encompassed by this disclosure differ from one another will be readily apparent to those skilled in the art. See, eg, Remington's Pharmaceutical Sciences, 18th Ed., Mack Publishing, Easton, PA (1990).

In one embodiment, the pharmaceutical compositions of this disclosure suitable for oral administration are in discrete form such as, but not limited to, tablets (e.g., chewable tablets), caplets, capsules and liquids (e.g., flavored syrups). It can be presented as a dosage form. Typical oral dosage forms of the present disclosure are prepared by combining the active ingredient in an intimate admixture with at least one excipient according to conventional pharmaceutical compounding techniques. Excipients can take a wide variety of forms depending on the form of preparation desired for administration. Non-limiting examples of excipients suitable for use in oral liquid or aerosol dosage forms include water, glycols, oils, alcohols, flavoring agents, preservatives and coloring agents. Non-limiting examples of excipients suitable for use in solid oral dosage forms such as powders, tablets, capsules and caplets include starches, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants. agents, binders and disintegrants.

Non-limiting examples of excipients that can be used in oral dosage forms of the disclosure include binders, fillers, disintegrants and lubricants. Non-limiting examples of binders suitable for use in pharmaceutical compositions and dosage forms include corn starch, potato starch or other starches, gelatin, natural and synthetic gums such as gum acacia, sodium alginate, alginic acid, etc. alginate, tragacanth powder, guar gum, cellulose and its derivatives (e.g., ethylcellulose, cellulose acetate, carboxymethylcellulose calcium, carboxymethylcellulose sodium), polyvinylpyrrolidone, methylcellulose, pregelatinized starch, hydroxypropylmethylcellulose, microcrystalline cellulose and their mixtures.

Non-limiting examples of fillers suitable for use in the pharmaceutical compositions and dosage forms disclosed herein include talc, calcium carbonate (eg granules or powders), microcrystalline cellulose, powdered cellulose. , dextran, kaolin, mannitol, silicic acid, sorbitol, starch, pregelatinized starch and mixtures thereof. The binder or filler in pharmaceutical compositions of this disclosure is typically present in from about 50 to about 99 weight percent of the pharmaceutical composition or dosage form.

Non-limiting examples of disintegrants that can be used in the pharmaceutical compositions and dosage forms of this disclosure include agar, alginic acid, calcium carbonate, microcrystalline cellulose, croscarmellose sodium, crospovidone, polacrilin potassium, Sodium starch glycolate, potato or tapioca starch, other starches, pregelatinized starches, other starches, clays, other algins, other celluloses, gums and mixtures thereof.

Non-limiting examples of lubricants that can be used in the pharmaceutical compositions and dosage forms of this disclosure include calcium stearate, magnesium stearate, mineral oil, light mineral oil, glycerin, sorbitol, mannitol, polyethylene glycol, and others. Glycol, stearic acid, sodium lauryl sulfate, talc, hydrogenated vegetable oils (e.g. peanut, cottonseed, sunflower, sesame, olive, corn and soybean oils), zinc stearate, ethyl oleate, ethyl laurate, agar and others A mixture of Examples of additional lubricants include syloid silica gel, coagulated aerosols of synthetic silica, CAB-O-SIL (a pyrogenic silicon dioxide product sold by Cabot Corp., Boston, Mass.), and mixtures thereof. be done. Lubricants, when used, are typically used in amounts of less than about 1% by weight of the pharmaceutical composition or dosage form in which they are incorporated.

Active ingredients or ingredients of the disclosure can be administered by controlled release means or by delivery devices or dosage forms that are well known to those of ordinary skill in the art. Non-limiting examples of controlled release means or delivery devices include U.S. Pat. Nos. 3,845,770; 3,916,899; 3,536,809; 3,598,123; , 5,591,767, 5,120,548, 5,073,543, 5,639,476, 5,354,556 and 5,733,566, which are incorporated herein by reference. there is For example, hydropropylmethylcellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multi-layer coatings, microparticles, liposomes, etc., can be used to provide desired release profiles in varying proportions using such dosage forms. Delayed or controlled release of one or more active ingredients can be provided using microspheres or combinations thereof. Suitable controlled-release formulations known to those of ordinary skill in the art, including those disclosed herein, can be readily selected for use with the active ingredients or active ingredients of the present disclosure. Accordingly, the present disclosure encompasses unit dosage forms suitable for oral administration such as, but not limited to, tablets, capsules, gelcaps, and caplets that are adapted for controlled release and are adapted for controlled release.

Parenteral dosage forms can be administered to patients by a variety of routes including, but not limited to, subcutaneous, intravenous (including bolus injection), intramuscular, and intraarterial. Because their administration typically bypasses patients' natural defenses against contaminants, parenteral dosage forms are preferably sterile or capable of being sterilized prior to administration to a patient. Non-limiting examples of parenteral dosage forms include ready-to-inject solutions, dry products that are readily dissolved or suspended in pharmaceutically acceptable vehicles for injection, ready-to-inject suspensions and emulsions. be done. Suitable vehicles that can be used to provide parenteral dosage forms of the disclosure are well known to those skilled in the art. Non-limiting examples of suitable vehicles include Water for Injection (United States Pharmacopoeia); aqueous vehicles such as, but not limited to, Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection; lactated Ringer's injection, and the like; water-miscible vehicles such as, but not limited to, ethyl alcohol, polyethylene glycol and polypropylene glycol; and non-aqueous vehicles, such as, but not limited to, corn oil, cottonseed oil, peanut oil, sesame oil, olein. ethyl acetate, isopropyl myristate and benzyl benzoate;

The drug can be applied topically to the skin and its appendages or to various mucous membranes. Routes that can be used include sublingual, nasal, vaginal, intracystic, rectal, preputial, intraocular, intrabuccal or intraaural. Many dosage forms have been developed to deliver active agents to the site of application to produce local action. Non-limiting examples of topical and mucosal dosage forms of the present disclosure include ointments, creams, gels, pastes, powders, lotions, sprays, paints, poultices, aerosols, liquids , emulsions, suspensions, eye drops or other ophthalmic preparations or other dosage forms known to those skilled in the art. See Remington's Pharmaceutical Sciences, 18th Ed., Mack Publishing, Easton, PA (1990); Introduction to Pharmaceutical Dosage Forms, Lea & Febiger, Philadelphia (1985). Dosage forms suitable for treating mucosal tissue in the oral cavity can be formulated as mouthwashes or oral gels.

Suitable excipients (e.g., carriers and diluents) and other materials that can be used to provide topical and mucosal dosage forms encompassed by this disclosure are well known to those skilled in the pharmaceutical arts, and the specific tissue to which a given pharmaceutical composition or dosage form is applied. Non-limiting examples of typical excipients for forming solutions, emulsions or gels include water, acetone, ethanol, ethylene glycol, propylene glycol, butane-1,3-diol, isopropyl myristate, Isopropyl palmitate, mineral oil and mixtures thereof, which are non-toxic and pharmaceutically acceptable.

Wetting agents such as occlusives, humectants, emollients and protein rejuvenators can also be added to pharmaceutical compositions and dosage forms if desired.

Occlusive agents are substances that physically block the loss of water within the stratum corneum. Non-limiting examples of occlusive agents include petroleum jelly, lanolin, mineral oil, silicones such as dimethicone, zinc oxide and combinations thereof. Preferred occlusive agents are petrolatum and lanolin, more preferably petrolatum at a minimum concentration of 5%.

Moisturizers are substances that, when applied to the skin, attract water to the skin and theoretically improve hydration of the stratum corneum. But the water that is attracted to the skin is water from other cells, not atmospheric water. Moisturizers of this type may continue to evaporate from the skin and actually exacerbate the dryness. Non-limiting examples of humectants include glycerin, sorbitol, urea, alpha hydroxy acids, sugars and combinations thereof. Preferred humectants include alpha hydroxy acids such as glycolic acid, lactic acid, malic acid, citric acid, tartaric acid, and the like.

An emollient is a substance that lubricates the skin by filling the spaces between skin flakes with oil droplets and is usually not occlusive unless thickly applied. When used in conjunction with emulsifiers, these can help retain oil and moisture within the stratum corneum. Vitamin E is a common additive that appears to have no effect, other than as an emollient. Other vitamins are added as well, such as vitamin A and vitamin D, but their action is questionable. Non-limiting examples of emollients include mineral oil, lanolin, fatty acids, cholesterol, squalene, structured lipids and combinations thereof.

The timing of administration of the compounds of the present disclosure and their therapeutic agents is not limited, and they may be administered simultaneously or at intervals (i.e., at different times) to the subject to whom they are administered. . Combinations of the compounds of the present disclosure and their therapeutic agents may also be used. The dosage of these therapeutic agents can be appropriately selected based on the clinically used dosage. In addition, the compounding ratio of the compounds of the present disclosure and their therapeutic agents can be appropriately selected depending on the subject to be administered, the administration route, the target disease, disorder or symptom, the age or weight of the subject, or a combination thereof. can be done.

In one embodiment of the present disclosure, compounds of the present disclosure can be administered in combination, either simultaneously or at different times, in using the pharmaceutical composition. Such pharmaceutical compositions are also within the scope of this disclosure.

Toxicity and therapeutic efficacy of compounds of the present disclosure can be determined, for example, by measuring _LD50 (the dose lethal to 50% of the population) and _ED50 (the dose therapeutically effective in 50% of the population). , can be determined by standard pharmaceutical procedures in cultured cells or experimental animals. The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio _LD50 / _ED5O .
Compounds that exhibit large therapeutic indices are preferred. Compounds that exhibit toxic side effects can be used, but delivery systems that target such compounds to the affected tissue site to minimize potential damage to uninfected cells and thereby reduce side effects. should be carefully designed.

The data obtained from cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED ₅₀ with little or no toxicity. The dosage may vary within this range depending on the dosage form employed and the route of administration utilized. For any compound used in the method of the disclosure, the therapeutically sufficient dose can be estimated initially from cell culture assays. A dose can be formulated in animal models to achieve a circulating plasma concentration range that includes the _IC50 (ie, the concentration of the test compound that achieves half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Plasma levels can be measured, for example, by high performance liquid chromatography.

The compounds of the present disclosure can be administered orally and in single or divided daily doses of from about 0.10 to about 150 mg/day, parenterally, topically, or transmucosally, calculated as active ingredient. , for example nasally, rectally or transdermally, or topically. The amount of pharmaceutical composition administered in the methods of the present disclosure will depend on the individual being treated, the severity of the disorder or symptoms of the disorder, the method of administration, the frequency of administration and the judgment of the physician. Dosing frequencies range from about hourly dosing to monthly dosing. In specific embodiments, administration is from 8 times daily up to once every other day, or 1-3 times/day. In a specific embodiment, pharmaceutical compositions of this disclosure are administered chronically, eg, daily.

In this specification, "or" is used when "at least one or more" of the items listed in the sentence can be employed. The same applies to "or". When "within a range of two values" is stated herein, the range includes the two values themselves.

References such as scientific articles, patents, patent applications, etc., cited herein are hereby incorporated by reference in their entirety to the same extent as if each were specifically set forth.

The present disclosure has been described above showing preferred embodiments for ease of understanding. While the present disclosure will now be described based on the examples, the foregoing description and the following examples are provided for illustrative purposes only and not for the purpose of limiting the present disclosure. Accordingly, the scope of the present disclosure is not limited to the embodiments or examples specifically described herein, but only by the claims.

In this example, examples relating to the production and use of the compounds of the present disclosure are described. In the following examples, where applicable, experiments were conducted in the spirit of animal welfare, and where applicable, medical ethical regulations such as the Declaration of Helsinki were observed.
The reagents used are each available as indicated, but others from Tokyo Kasei Kogyo, Fujifilm Wako Pure Chemical, Sigma-Aldrich, Kanto Kagaku, Enamine, and Combi-Blocks can also be used.

As thin layer chromatography (TLC), Merck's TLC Silica gel 60 F254 (25 glass plates, 20 x 20 cm; thickness: 0.25 mm; product number: 1.05715.0001) and Fuji CHROMATOREX NH-TLC Plates (20×20 cm; thickness 0.2 mm) manufactured by Silysia Chemical were used. Spots were confirmed by color development with UV irradiation, ninhydrin, iodine, or phosphomolybdic acid (ethanol solution). Drying of the organic solvent was performed using anhydrous sodium sulfate and anhydrous magnesium sulfate. For column chromatography, cartridge columns CHROMATOREX Q-PACK SI30 (SIZE 10, 20 or 60) and NH30 (SIZE 10 or 20) manufactured by Fuji Silysia Chemical were used according to the amount of crude product to be purified. Preparative Silica Gel Thin Layer Chromatography (PTLC) was performed on a Merck PLC Silica gel 60 F254 (20 x 20 cm; thickness: 0.5 mm; item number: 1.05744.0001 or thickness : 1.0 mm; product number: 1.13895.0001) and CHROMATOREX NH-PLC05 (20 x 20 cm; thickness: 0.5 mm) manufactured by Fuji Silysia Chemical.
The synthesized compounds were identified by LC/MS (Liquid Chromatography/Mass Spectrometry), and the retention times (RT) and m/z values [M + H] + or [M + Na] +, [M + H-Boc] +, [ M+H−tBu]+, etc. An LCMS-2020 system manufactured by Shimadzu Corporation was used for the measurement, and L-column 2 ODS, 3 μm, 3.0×50 mm manufactured by the Chemical Evaluation and Research Institute was used as an analysis column. The column oven was set at 40° C., and the compounds were detected using both ultraviolet absorption (220 nm, 254 nm) and mass spectrometry. The following elution conditions were used.

Elution conditions:
Flow rate 1.5 mL/min, mobile phase a = 0.05% (v/v) trifluoroacetic acid aqueous solution, mobile phase b = 0.05% (v/v) trifluoroacetic acid-containing acetonitrile; 0-0.9 minutes Linear gradient a:b (95:5) to a:b (10:90), 0.9-2 min a:b (10:90).

Nuclear magnetic resonance (NMR) was measured using a Bruker AVANCE III 300 MHz Spectrometer (resonant frequencies: ¹ H: 300 MHz, ¹³ C: 75 MHz).

In the Examples, the abbreviations set forth above and the abbreviations set forth below may be used for ease of description.
s: singlet d: doublet t: triplet m: multiplet dd: doublet of doublets J: coupling constant
Hz: Hertz
δ: chemical shift min: minutes
RT: retention time CDCl ₃ : deuterated chloroform Boc: tert-butoxycarbonyl Ns: 2-nitrobenzenesulfonyl HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b] pyridinium 3-oxide hexafluorophosphate DMT-MM: 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride

(Example 1: Synthesis of compound)

２－｛（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－ベンジル－８－［（２－ニトロフェニル）スルホニル］－１－オキソ－１，２，３，６，７，７ａ－ヘキサヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド｝エチルフェニルカーボネイト（中間体１－１）の合成
１－［（２－ニトロフェニル)スルホニル）－１Ｈ－ピロール－２－カルバルデヒド（０．５０ｇ）を２，２，２－トリフルオロエタノール（３．６ｍＬ）に懸濁させた後、ベンジルアミン（２１５μＬ）を加え、室温にて１．５時間撹拌した。反応溶液に２－イソシアノエチルフェニルカーバメイト（４０９ｍｇ）、アクリル酸（１４７μＬ）を添加し、さらに３日間撹拌した。反応溶液を減圧濃縮し、得られた残渣をＮ，Ｎ－ジメチルアセトアミド（３．６ｍＬ）に溶解させ、１２０℃（オイルバス設定温度）にて２５時間撹拌した。反応溶液を室温まで冷却後、酢酸エチル及び１ｍｏｌ／Ｌ塩酸水溶液を加え、有機層を分離した。得られた有機層を飽和炭酸水素ナトリウム水溶液、及び飽和食塩水にて洗浄した後、無水硫酸ナトリウムにて乾燥した。ろ過、溶媒の減圧留去により得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ２０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製することにより、標題化合物（７７５ｍｇ， 収率６９％， ＲＴ＝１．０８分， ［Ｍ＋Ｈ］＋＝６３３）を黄色アモルファスとして得た。
^１Ｈ－ＮＭＲ（３００ＭＨｚ， ＣＤＣｌ_３）： δ ７．９２－７．８８ （ｍ， １Ｈ）， ７．６８－７．６３ （ｍ， ２Ｈ）， ７．５４－７．５０ （ｍ， １Ｈ）， ７．４４－７．３９ （ｍ， ２Ｈ）， ７．３４－７．２６ （ｍ， ６Ｈ）， ７．２０－７．１６ （ｍ， ２Ｈ）， ６．４２ （ｔ， Ｊ ＝ ５．５ Ｈｚ， １Ｈ）， ６．１８ （ｄ， Ｊ ＝ ５．７ Ｈｚ， １Ｈ）， ６．００ （ｄｄ， Ｊ ＝ ５．７， ２．１ Ｈｚ， １Ｈ）， ４．９８ （ｄｄ， Ｊ ＝ ４．０， ２．１ Ｈｚ， １Ｈ）， ４．９５ （ｓ， １Ｈ）， ４．５９ （ｄ， Ｊ ＝ １５．０ Ｈｚ， １Ｈ）， ４．４５ （ｄ， Ｊ ＝ １５．０ Ｈｚ， １Ｈ）， ４．２７－４．１１ （ｍ， ２Ｈ）， ３．５５－３．４７ （ｍ， ２Ｈ）， ２．９０ （ｄｄ， Ｊ ＝ ９．４， ４．０ Ｈｚ， １Ｈ）， ２．４３ （ｔｄ， Ｊ ＝ １３．０， ４．０ Ｈｚ， １Ｈ）， １．５５ （ｄｄ， Ｊ ＝ １３．０， ９．４ Ｈｚ， １Ｈ）． [Synthesis Example 1: Ugi Reaction/Intramolecular Diels-Alder Reaction]

2-{(3R ^* ,3aR ^* ,6S ^* ,7aS ^* )-2-benzyl-8-[(2-nitrophenyl)sulfonyl]-1-oxo-1,2,3,6,7,7a-hexahydro -Synthesis of 3a,6-epiiminoisoindole-3-carboxamido}ethylphenyl carbonate (intermediate 1-1) 1-[(2-nitrophenyl)sulfonyl)-1H-pyrrole-2-carbaldehyde (0.50 g) ) was suspended in 2,2,2-trifluoroethanol (3.6 mL), benzylamine (215 μL) was added, and the mixture was stirred at room temperature for 1.5 hours. 2-Isocyanoethylphenylcarbamate (409 mg) and acrylic acid (147 μL) were added to the reaction solution, and the mixture was further stirred for 3 days. The reaction solution was concentrated under reduced pressure, and the obtained residue was dissolved in N,N-dimethylacetamide (3.6 mL) and stirred at 120° C. (oil bath set temperature) for 25 hours. After cooling the reaction solution to room temperature, ethyl acetate and 1 mol/L hydrochloric acid aqueous solution were added to separate the organic layer. The obtained organic layer was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The title compound ( 775 mg, 69% yield, RT=1.08 min, [M+H]+=633) was obtained as a yellow amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.92-7.88 (m, 1H), 7.68-7.63 (m, 2H), 7.54-7.50 (m, 1H) , 7.44-7.39 (m, 2H), 7.34-7.26 (m, 6H), 7.20-7.16 (m, 2H), 6.42 (t, J = 5. 5 Hz, 1H), 6.18 (d, J = 5.7 Hz, 1H), 6.00 (dd, J = 5.7, 2.1 Hz, 1H), 4.98 (dd, J = 4.0, 2.1 Hz, 1H), 4.95 (s, 1H), 4.59 (d, J = 15.0 Hz, 1H), 4.45 (d, J = 15.0 Hz, 1H), 4.27-4.11 (m, 2H), 3.55-3.47 (m, 2H), 2.90 (dd, J = 9.4, 4.0 Hz, 1H), 2 .43 (td, J = 13.0, 4.0 Hz, 1 H), 1.55 (dd, J = 13.0, 9.4 Hz, 1 H).

Intermediate 1 synthesized by changing the amine compound used is summarized in the table below.

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－ベンジル－８－［（２－ニトロフェニル）スルホニル］－１－オキソ－１，２，３，６，７，７ａ－ヘキサヒドロ－３ａ，６－エピイミノイソインドール－３－カルボン酸（中間体２－１）の合成
中間体１－１（７７５ｍｇ）をアセトニトリル（５．７ｍＬ）と水（０．３ｍＬ）の混合溶液に懸濁させた後、炭酸セシウム（１．２０ｇ）を加え、室温にて１６時間撹拌した。氷冷下、１ｍｏｌ／Ｌ塩酸水溶液を加えることで反応溶液のｐＨを１～２に調整した後、酢酸エチルにて抽出を行った。得られた有機層は無水硫酸ナトリウムにて乾燥した後、ろ過、溶媒の減圧留去を行った。得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ２０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１，次いで酢酸エチル：メタノール １：０－３：２）にて精製することにより、標題化合物（４４５ｍｇ， 収率７７％， ＲＴ＝０．９５分， ［Ｍ＋Ｈ］＋＝４７０）を黄色アモルファスとして得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．７８ （ｄｄ， Ｊ ＝ ７．７， １．３ Ｈｚ， １Ｈ）， ７．７２－７．５６ （ｍ， ３Ｈ）， ７．３１－７．２６ （ｍ， ５Ｈ）， ６．１７ （ｄｄ， Ｊ ＝ ５．９， ２．１ Ｈｚ， １Ｈ）， ６．１１ （ｄ， Ｊ ＝ ５．９ Ｈｚ， １Ｈ）， ５．２３ （ｓ， １Ｈ）， ５．０６ （ｄｄ， Ｊ ＝ ４．０， ２．１ Ｈｚ， １Ｈ）， ４．５９ （ｄ， Ｊ ＝ １５．５ Ｈｚ， １Ｈ）， ４．４７ （ｄ， Ｊ ＝ １５．５ Ｈｚ， １Ｈ）， ２．７８ （ｄｄ， Ｊ ＝ ９．４， ４．０ Ｈｚ， １Ｈ）， ２．４０ （ｔｄ， Ｊ ＝ １１．７， ４．０ Ｈｚ， １Ｈ）， １．５３ （ｄｄ， Ｊ ＝ １１．７， ９．４ Ｈｚ， １Ｈ）． [Synthesis Example 2: Hydrolysis reaction]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-benzyl-8-[(2-nitrophenyl)sulfonyl]-1-oxo-1,2,3,6,7,7a-hexahydro-3a, Synthesis of 6-epiiminoisoindole-3-carboxylic acid (Intermediate 2-1) Intermediate 1-1 (775 mg) was suspended in a mixed solution of acetonitrile (5.7 mL) and water (0.3 mL). After that, cesium carbonate (1.20 g) was added, and the mixture was stirred at room temperature for 16 hours. Under ice-cooling, a 1 mol/L aqueous solution of hydrochloric acid was added to adjust the pH of the reaction solution to 1 to 2, followed by extraction with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate, filtered, and the solvent was distilled off under reduced pressure. Purify the obtained residue by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE20, eluent: hexane:ethyl acetate 4:1-0:1, then ethyl acetate:methanol 1:0-3:2). afforded the title compound (445 mg, 77% yield, RT=0.95 min, [M+H]+=470) as a yellow amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.78 (dd, J = 7.7, 1.3 Hz, 1H), 7.72-7.56 (m, 3H), 7.31- 7.26 (m, 5H), 6.17 (dd, J = 5.9, 2.1 Hz, 1H), 6.11 (d, J = 5.9 Hz, 1H), 5.23 (s , 1 H), 5.06 (dd, J = 4.0, 2.1 Hz, 1 H), 4.59 (d, J = 15.5 Hz, 1 H), 4.47 (d, J = 15. 5 Hz, 1 H), 2.78 (dd, J = 9.4, 4.0 Hz, 1 H), 2.40 (td, J = 11.7, 4.0 Hz, 1 H), 1.53 ( dd, J = 11.7, 9.4 Hz, 1H).

Intermediate 2 synthesized by changing Intermediate 1 used as a starting material is summarized in the table below.

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－ベンジル－Ｎ－イソブチル－８－［（２－ニトロフェニル）スルホニル］－１－オキソ－１，２，３，６，７，７ａ－ヘキサヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（中間体３－１）の合成
中間体２－１（２２２ｍｇ）をＮ，Ｎ-ジメチルホルムアミド（１．０ｍＬ）に溶解させた後、イソブチルアミン（０．５７ｍＬ）、ＨＡＴＵ（２７０ｍｇ）、Ｎ，Ｎ，－ジイソプロピルエチルアミン（０．２４ｍＬ）を順次添加し、室温にて１時間撹拌した。反応溶液に１ｍｏｌ／Ｌ塩酸水溶液を加えることで反応を停止し、酢酸エチルにて抽出を行った。得られた有機相を硫酸ナトリウムにて乾燥した。ろ過、溶媒の減圧留去により得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＮＨ３０ ＳＩＺＥ２０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製することにより、標題化合物（２１４ｍｇ， 収率８７％， ＲＴ＝１．０７分， ［Ｍ＋Ｈ］＋＝５２５）を白色固体として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．９３－７．８９ （ｍ， １Ｈ）， ７．７１－７．６５ （ｍ， ２Ｈ）， ７．６１－７．５８ （ｍ， １Ｈ）， ７．３２－７．２７ （ｍ， ５Ｈ）， ６．１２－６．０２ （ｍ， ３Ｈ）， ５．００ （ｄｄ， Ｊ ＝ ４．０， ２．１ Ｈｚ， １Ｈ）， ４．９３ （ｓ， １Ｈ）， ４．５８ （ｄ， Ｊ ＝ １４．７ Ｈｚ， １Ｈ）， ４．４６ （ｄ， Ｊ ＝ １４．７ Ｈｚ， １Ｈ）， ３．０３－２．８４ （ｍ， ３Ｈ）， ２．４３ （ｔｄ， Ｊ ＝ ７．９， ３．９ Ｈｚ， １Ｈ）， １．６４－１．５２ （ｍ， ２Ｈ）， ０．８５ （ｄ， Ｊ ＝ ６．８ Ｈｚ， ６Ｈ）． [Synthesis Example 3: Condensation reaction]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-benzyl-N-isobutyl-8-[(2-nitrophenyl)sulfonyl]-1-oxo-1,2,3,6,7,7a- Synthesis of hexahydro-3a,6-epiiminoisoindole-3-carboxamide (Intermediate 3-1) Intermediate 2-1 (222 mg) was dissolved in N,N-dimethylformamide (1.0 mL), followed by isobutyl Amine (0.57 mL), HATU (270 mg) and N,N,-diisopropylethylamine (0.24 mL) were sequentially added and stirred at room temperature for 1 hour. A 1 mol/L hydrochloric acid aqueous solution was added to the reaction solution to stop the reaction, and the mixture was extracted with ethyl acetate. The obtained organic phase was dried with sodium sulfate. The title compound ( 214 mg, 87% yield, RT=1.07 min, [M+H]+=525) as a white solid.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.93-7.89 (m, 1H), 7.71-7.65 (m, 2H), 7.61-7.58 (m, 1H ), 7.32-7.27 (m, 5H), 6.12-6.02 (m, 3H), 5.00 (dd, J = 4.0, 2.1 Hz, 1H), 4. 93 (s, 1H), 4.58 (d, J = 14.7 Hz, 1H), 4.46 (d, J = 14.7 Hz, 1H), 3.03-2.84 (m, 3H ), 2.43 (td, J = 7.9, 3.9 Hz, 1H), 1.64-1.52 (m, 2H), 0.85 (d, J = 6.8 Hz, 6H) .

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－ベンジル－Ｎ－（ナフタレン－１－イルメチル）－８－［（２－ニトロフェニル）スルホニル］－１－オキソ－１，２，３，６，７，７ａ－ヘキサヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（中間体３－１０）の合成
１－［（２－ニトロフェニル)スルホニル）－１Ｈ－ピロール－２－カルバルデヒド（１．００ｇ）を２，２，２－トリフルオロエタノール（７．０ｍＬ）に懸濁させた後、ベンジルアミン（０．４７ｍＬ）を加え、室温にて１時間撹拌した。反応溶液に１－（イソシアノメチル）ナフタレン（０．７８ｇ）、アクリル酸（０．３２ｍＬ）を添加し、さらに２６時間撹拌した。反応溶液を減圧濃縮し、得られた残渣をＮ，Ｎ－ジメチルアセトアミド（７．０ｍＬ）に溶解させ、１２０℃（オイルバス設定温度）にて１７時間撹拌した。反応溶液を室温まで冷却後、酢酸エチル及び１ｍｏｌ／Ｌ塩酸水溶液を加え、有機相を分離した。得られた有機相を飽和炭酸水素ナトリウム水溶液、及び飽和食塩水にて洗浄した後、無水硫酸ナトリウムにて乾燥した。ろ過、溶媒の減圧留去により得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ６０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製した。得られた固体をメタノールにて洗浄、減圧下４０℃にて乾燥することにより標題化合物（１．１２ｇ， 収率５２％， ＲＴ＝１．１４分， ［Ｍ＋Ｈ］＋＝６０９）を灰色固体として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．９３－７．８４ （ｍ， ４Ｈ）， ７．７０－７．５８ （ｍ， ２Ｈ）， ７．５６－７．４８ （ｍ， ３Ｈ）， ７．４４ （ｄｄ， Ｊ ＝ ８．１， ７．０ Ｈｚ， １Ｈ）， ７．３２－７．３０ （ｍ， １Ｈ）， ７．２２－７．１３ （ｍ， ５Ｈ）， ６．３０ （ｔ， Ｊ ＝ ５．７ Ｈｚ， １Ｈ）， ６．０７ （ｄ， Ｊ ＝ ５．７ Ｈｚ， １Ｈ）， ６．０２ （ｄｄ， Ｊ ＝ ５．７， ２．１ Ｈｚ， １Ｈ）， ４．９８ （ｔ， Ｊ ＝ ２．１ Ｈｚ， １Ｈ）， ４．９６ （ｓ， １Ｈ）， ４．８７ （ｄｄ， Ｊ ＝ １４．５， ５．７ Ｈｚ， １Ｈ）， ４．６２ （ｄｄ， Ｊ ＝ １４．５， ５．７ Ｈｚ， １Ｈ）， ４．５３ （ｄ， Ｊ ＝ １４．７ Ｈｚ， １Ｈ）， ４．４０ （ｄ， Ｊ ＝ １４．７ Ｈｚ， １Ｈ）， ２．７８ （ｄｄ， Ｊ ＝ ９．４， ４．０ Ｈｚ， １Ｈ）， ２．３８ （ｔｄ， Ｊ ＝ １２．１， ４．０ Ｈｚ， １Ｈ）， １．５１ （ｄｄ， Ｊ ＝ １２．１， ９．４ Ｈｚ， １Ｈ）． [Synthesis Example 4: Ugi Reaction/Intramolecular Diels-Alder Reaction]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-benzyl-N-(naphthalen-1-ylmethyl)-8-[(2-nitrophenyl)sulfonyl]-1-oxo-1,2,3, Synthesis of 6,7,7a-hexahydro-3a,6-epiiminoisoindole-3-carboxamide (Intermediate 3-10) 1-[(2-Nitrophenyl)sulfonyl)-1H-pyrrole-2-carbaldehyde ( 1.00 g) was suspended in 2,2,2-trifluoroethanol (7.0 mL), benzylamine (0.47 mL) was added, and the mixture was stirred at room temperature for 1 hour. 1-(Isocyanomethyl)naphthalene (0.78 g) and acrylic acid (0.32 mL) were added to the reaction solution, and the mixture was further stirred for 26 hours. The reaction solution was concentrated under reduced pressure, and the resulting residue was dissolved in N,N-dimethylacetamide (7.0 mL) and stirred at 120° C. (oil bath set temperature) for 17 hours. After cooling the reaction solution to room temperature, ethyl acetate and 1 mol/L hydrochloric acid aqueous solution were added to separate the organic phase. The obtained organic phase was washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine, and then dried over anhydrous sodium sulfate. The residue obtained by filtration and evaporation of the solvent under reduced pressure was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE60, eluent: hexane:ethyl acetate 4:1-0:1). The obtained solid was washed with methanol and dried at 40° C. under reduced pressure to give the title compound (1.12 g, yield 52%, RT=1.14 min, [M+H]+=609) as a gray solid. Obtained.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.93-7.84 (m, 4H), 7.70-7.58 (m, 2H), 7.56-7.48 (m, 3H ), 7.44 (dd, J = 8.1, 7.0 Hz, 1H), 7.32-7.30 (m, 1H), 7.22-7.13 (m, 5H), 6. 30 (t, J = 5.7 Hz, 1 H), 6.07 (d, J = 5.7 Hz, 1 H), 6.02 (dd, J = 5.7, 2.1 Hz, 1 H), 4.98 (t, J = 2.1 Hz, 1H), 4.96 (s, 1H), 4.87 (dd, J = 14.5, 5.7 Hz, 1H), 4.62 (dd , J = 14.5, 5.7 Hz, 1H), 4.53 (d, J = 14.7 Hz, 1H), 4.40 (d, J = 14.7 Hz, 1H), 2.78 (dd, J = 9.4, 4.0 Hz, 1H), 2.38 (td, J = 12.1, 4.0 Hz, 1H), 1.51 (dd, J = 12.1, 9 .4 Hz, 1 H).

Intermediate 2 used in Synthesis Example 3 and Intermediate 3 synthesized by changing the amine compound are summarized in the table below. Intermediate 3 synthesized by changing the amine compound and isonitrile compound used in Synthesis Example 4 is also summarized in the table below.

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－Ｎ，２－ジベンジル－１－オキソ－１，２，３，６，７，７ａ－ヘキサヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（中間体４－１）の合成
（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－Ｎ，２－ジベンジル－８－［（２－ニトロフェニル）スルホニル］－１－オキソ－１，２，３，６，７，７ａ－ヘキサヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（Ｊ．Ｏｒｇ．Ｃｈｅｍ． ２０１４、 １２０７－１２１４ 記載化合物， ９５．２ｍｇ）をアセトニトリル（１．７ｍＬ）に懸濁させ、炭酸セシウム（１１１ｍｇ）、１－チオグリセロール（２９．０μＬ）を順次添加した後、５０℃（オイルバス設定温度）にて１９時間撹拌した。反応溶液を室温まで冷却後、不溶物をろ過にて取り除き、溶媒を減圧濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＮＨ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ９：１－０：１）にて精製することにより、標題化合物（４３．１ｍｇ， 収率６８％， ＲＴ＝０．７７分， ［Ｍ＋Ｈ］＋＝３７４）を黄色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．３７－７．２１ （ｍ， １０Ｈ）， ６．７０ （ｔ， Ｊ ＝ ５．９ Ｈｚ， １Ｈ）， ６．３７ （ｄｄ， Ｊ ＝ ５．３， １．９ Ｈｚ， １Ｈ）， ６．２８ （ｄ， Ｊ ＝ ５．３ Ｈｚ， １Ｈ）， ４．９１ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ４．５１ （ｄｄ， Ｊ ＝ １４．５， ５．９ Ｈｚ， １Ｈ）， ４．３１ （ｄｄ， Ｊ ＝ １４．５， ５．９ Ｈｚ， １Ｈ）， ４．２２ （ｄｄ， Ｊ ＝ ３．８， １．９ Ｈｚ， １Ｈ）， ４．１１ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ４．００ （ｓ， １Ｈ）， ２．４４ （ｄｄ， Ｊ ＝ ９．１， ３．８ Ｈｚ， １Ｈ）， ２．１９ （ｔｄ， Ｊ ＝ １１．７， ３．８ Ｈｚ， １Ｈ）， １．４２ （ｄｄ， Ｊ ＝ １１．７， ９．１ Ｈｚ， １Ｈ）． [Synthesis Example 5: Deprotection reaction of Ns group]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-N,2-dibenzyl-1-oxo-1,2,3,6,7,7a-hexahydro-3a,6-epiiminoisoindole-3-carboxamide Synthesis of (Intermediate 4-1) (3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-N,2-dibenzyl-8-[(2-nitrophenyl)sulfonyl]-1-oxo-1,2,3 ,6,7,7a-hexahydro-3a,6-epiiminoisoindole-3-carboxamide (J.Org.Chem. 2014, 1207-1214 described compound, 95.2 mg) was suspended in acetonitrile (1.7 mL). Cesium carbonate (111 mg) and 1-thioglycerol (29.0 μL) were sequentially added, and the mixture was stirred at 50° C. (oil bath set temperature) for 19 hours. After cooling the reaction solution to room temperature, insoluble matter was removed by filtration, and the solvent was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (CHROMATOREX Q-PACK NH30 SIZE 10, eluent: hexane:ethyl acetate 9:1-0:1) to give the title compound (43.1 mg, yield 68% , RT=0.77 min, [M+H]+=374) as a yellow oil.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.37-7.21 (m, 10H), 6.70 (t, J = 5.9 Hz, 1H), 6.37 (dd, J = 5.3, 1.9 Hz, 1H), 6.28 (d, J = 5.3 Hz, 1H), 4.91 (d, J = 15.1 Hz, 1H), 4.51 (dd, J = 14.5, 5.9 Hz, 1H), 4.31 (dd, J = 14.5, 5.9 Hz, 1H), 4.22 (dd, J = 3.8, 1.9 Hz , 1H), 4.11 (d, J = 15.1 Hz, 1H), 4.00 (s, 1H), 2.44 (dd, J = 9.1, 3.8 Hz, 1H), 2 .19 (td, J=11.7, 3.8 Hz, 1 H), 1.42 (dd, J=11.7, 9.1 Hz, 1 H).

Intermediate 4 synthesized by changing Intermediate 3 used as a starting material is summarized in the table below.

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－Ｎ，２－ジベンジル－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（中間体５－１）の合成
中間体４－１（２１７ｍｇ）をメタノール（３．０ｍＬ）に溶解させ、パラジウム／炭素（Ｐｄ１０％）（３１ｍｇ）を加えた後、水素雰囲気下、室温にて６時間撹拌した。反応溶液をセライトろ過した後、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＮＨ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製した。得られた固体をヘキサンにて洗浄した後、減圧下４０℃で乾燥することにより標題化合物（１７０ｍｇ， 収率７８％， ＲＴ＝０．７６分， ［Ｍ＋Ｈ］＋＝３７６）を白色固体として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．４０－７．２０ （ｍ， １０Ｈ）， ６．０４－６．０２ （ｍ， １Ｈ）， ４．９３ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ４．４７ （ｄｄ， Ｊ ＝ １４．７， ５．３ Ｈｚ， １Ｈ）， ４．２６ （ｄｄ， Ｊ ＝ １４．７， ５．３ Ｈｚ， １Ｈ）， ４．０６ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ３．９６ （ｓ， １Ｈ）， ３．７０ （ｔ， Ｊ ＝ ４．５ Ｈｚ， １Ｈ）， ２．６４ （ｄｄ， Ｊ ＝ ９．４， ４．５ Ｈｚ， １Ｈ）， ２．０１－１．９４ （ｍ， １Ｈ）， １．８４－１．６６ （ｍ， ３Ｈ）， １．５２－１．４８ （ｍ， ２Ｈ）． [Synthesis Example 6: Catalytic hydrogen reduction reaction]

(3R ^* ,3aR ^* ,6S ^* ,7aS ^* )-N,2-dibenzyl-1-oxooctahydro-3a,6-epiiminoisoindole-3-carboxamide (intermediate 5-1) synthesis intermediate 4 -1 (217 mg) was dissolved in methanol (3.0 mL), palladium/carbon (Pd 10%) (31 mg) was added, and the mixture was stirred at room temperature for 6 hours under a hydrogen atmosphere. After the reaction solution was filtered through celite, the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (CHROMATOREX Q-PACK NH30 SIZE 10, eluent: hexane:ethyl acetate 4:1-0:1). The resulting solid was washed with hexane and dried at 40°C under reduced pressure to give the title compound (170 mg, yield 78%, RT = 0.76 min, [M + H] + = 376) as a white solid. rice field.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.40-7.20 (m, 10H), 6.04-6.02 (m, 1H), 4.93 (d, J = 15.1 Hz, 1H), 4.47 (dd, J = 14.7, 5.3 Hz, 1H), 4.26 (dd, J = 14.7, 5.3 Hz, 1H), 4.06 (d , J = 15.1 Hz, 1H), 3.96 (s, 1H), 3.70 (t, J = 4.5 Hz, 1H), 2.64 (dd, J = 9.4, 4. 5 Hz, 1H), 2.01-1.94 (m, 1H), 1.84-1.66 (m, 3H), 1.52-1.48 (m, 2H).

Intermediate 5 synthesized by changing Intermediate 4 used as a starting material is summarized in the table below.

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－Ｎ，２－ジベンジル－８－（３－メチルブタノイル）－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号２６）の合成
中間体５－１（１３．５ｍｇ）をクロロホルム（０．５ｍＬ）と飽和炭酸水素ナトリウム水溶液（０．５ｍＬ）の混合溶液に溶解させた。イソバレリルクロリド（７．０μＬ）を添加し、室温にて１７時間撹拌した。有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した後、溶媒を減圧留去、得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製することにより、標題化合物（１４．１ｍｇ， 収率８５％， ＲＴ＝１．０７分， ［Ｍ＋Ｈ］＋＝４６０）を無色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．３８－７．１６ （ｍ， １０Ｈ）， ６．２３ （ｔ， Ｊ ＝ ５．７ Ｈｚ， １Ｈ）， ５．４１ （ｓ， １Ｈ）， ４．９５ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ４．３９ （ｄ， Ｊ ＝ ６．０ Ｈｚ， ２Ｈ）， ４．２６ （ｔ， Ｊ ＝ ４．５ Ｈｚ， １Ｈ）， ４．０３ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ２．９４ （ｑ， Ｊ ＝ ５．２ Ｈｚ， １Ｈ）， ２．２２－２．１３ （ｍ， ２Ｈ）， ２．０７－１．８０ （ｍ， ５Ｈ）， １．６９－１．５８ （ｍ， ２Ｈ）， ０．９２ （ｄ， Ｊ ＝ ６．４ Ｈｚ， ３Ｈ）， ０．８９ （ｄ， Ｊ ＝ ６．４ Ｈｚ， ３Ｈ）． [Synthesis Example 7: Coupling Reaction-1]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-N,2-dibenzyl-8-(3-methylbutanoyl)-1-oxooctahydro-3a,6-epiiminoisoindole-3-carboxamide (compound Synthetic intermediate 5-1 (13.5 mg) of No. 26) was dissolved in a mixed solution of chloroform (0.5 mL) and saturated aqueous sodium hydrogencarbonate solution (0.5 mL). Isovaleryl chloride (7.0 μL) was added and stirred at room temperature for 17 hours. After separating the organic layer using a Phase Separator, the solvent was distilled off under reduced pressure, and the obtained residue was subjected to silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE10, eluent: hexane:ethyl acetate 4:1-0:1). The title compound (14.1 mg, 85% yield, RT=1.07 min, [M+H]+=460) was obtained as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.38-7.16 (m, 10H), 6.23 (t, J = 5.7 Hz, 1H), 5.41 (s, 1H) , 4.95 (d, J = 15.1 Hz, 1H), 4.39 (d, J = 6.0 Hz, 2H), 4.26 (t, J = 4.5 Hz, 1H), 4 .03 (d, J = 15.1 Hz, 1H), 2.94 (q, J = 5.2 Hz, 1H), 2.22-2.13 (m, 2H), 2.07-1. 80 (m, 5H), 1.69-1.58 (m, 2H), 0.92 (d, J = 6.4 Hz, 3H), 0.89 (d, J = 6.4 Hz, 3H ).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－ベンジル－８－（２－メトキシアセチル）－Ｎ－（ナフタレン－１－イルメチル）－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号２３２）の合成
中間体５－１０（１０．０ｍｇ）をクロロホルム（１．０ｍＬ）に溶解させ、メトキシ酢酸（２．２μＬ）、ＨＡＴＵ（１３ｍｇ）、トリエチルアミン（１３μＬ）を順次添加し、室温にて１．５時間撹拌した。反応溶液に飽和炭酸水素ナトリウム水溶液を加えて反応を停止し、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＮＨ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製することにより、標題化合物（１０．４ｍｇ， 収率８７％， ＲＴ＝１．０５分， ［Ｍ＋Ｈ］＋＝４９８）を無色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．９８－７．８４ （ｍ， ３Ｈ）， ７．６３－７．５２ （ｍ， ２Ｈ）， ７．４７－７．３５ （ｍ， ２Ｈ）， ７．２１－６．９３ （ｍ， ５Ｈ）， ６．０９ （ｄ， Ｊ ＝ ５．３ Ｈｚ， １Ｈ）， ５．４０ （ｓ， １Ｈ）， ４．８９－４．７２ （ｍ， ３Ｈ）， ４．４２ （ｔ， Ｊ ＝ ４．３ Ｈｚ， １Ｈ）， ４．１４ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ３．９１ （ｄ， Ｊ ＝ １４．４ Ｈｚ， １Ｈ）， ３．８２ （ｄ， Ｊ ＝ １４．４ Ｈｚ， １Ｈ）， ３．３１ （ｓ， ３Ｈ）， ２．９６ （ｄｄ， Ｊ ＝ ９．８， ５．３ Ｈｚ， １Ｈ）， ２．１７－２．１４ （ｍ， １Ｈ）， １．９０－１．８３ （ｍ， ３Ｈ）， １．７０－１．５８ （ｍ， ２Ｈ）． [Synthesis Example 8: Coupling Reaction-2]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-benzyl-8-(2-methoxyacetyl)-N-(naphthalen-1-ylmethyl)-1-oxooctahydro-3a,6-epiiminoiso Synthetic intermediate 5-10 (10.0 mg) of indole-3-carboxamide (Compound No. 232) was dissolved in chloroform (1.0 mL), methoxyacetic acid (2.2 μL), HATU (13 mg), triethylamine (13 μL). was added sequentially and stirred at room temperature for 1.5 hours. A saturated sodium bicarbonate aqueous solution was added to the reaction solution to stop the reaction, and the organic layer was separated using a Phase Separator. The title compound ( 10.4 mg, 87% yield, RT=1.05 min, [M+H]+=498) as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.98-7.84 (m, 3H), 7.63-7.52 (m, 2H), 7.47-7.35 (m, 2H ), 7.21-6.93 (m, 5H), 6.09 (d, J = 5.3 Hz, 1H), 5.40 (s, 1H), 4.89-4.72 (m, 3H), 4.42 (t, J = 4.3 Hz, 1H), 4.14 (d, J = 15.1 Hz, 1H), 3.91 (d, J = 14.4 Hz, 1H) , 3.82 (d, J = 14.4 Hz, 1H), 3.31 (s, 3H), 2.96 (dd, J = 9.8, 5.3 Hz, 1H), 2.17- 2.14 (m, 1H), 1.90-1.83 (m, 3H), 1.70-1.58 (m, 2H).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２，８－ジイソブチル－Ｎ－イソペンチル－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号２５６）の合成
中間体５－５（１０．０ｍｇ）をクロロホルム（１．０ｍＬ）に溶解させ、イソブチルアルデヒド（４．２μＬ）、トリアセトキシ水素化ホウ素ナトリウム（２０ｍｇ）を順次添加し、室温にて１５時間撹拌した。反応溶液に飽和炭酸水素ナトリウム水溶液を加えて反応を停止し、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製することにより、標題化合物（９．３ｍｇ， 収率７９％， ＲＴ＝０．８４分， ［Ｍ＋Ｈ］＋＝３７８）を無色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ５．９５ （ｔ， Ｊ ＝ ５．３ Ｈｚ， １Ｈ）， ４．００ （ｓ， １Ｈ）， ３．５０ （ｄｄ， Ｊ ＝ １３．６， ９．６ Ｈｚ， １Ｈ）， ３．４２ （ｔ， Ｊ ＝ ５．３ Ｈｚ， １Ｈ）， ３．３８－３．２８ （ｍ， ２Ｈ）， ２．６５ （ｄｄ， Ｊ ＝ １３．６， ５．３ Ｈｚ， １Ｈ）， ２．４５ （ｄｄ， Ｊ ＝ ９．６， ４．５ Ｈｚ， １Ｈ）， ２．２１－２．０５ （ｍ， ２Ｈ）， １．９９－１．８４ （ｍ， ４Ｈ）， １．６７－１．５６ （ｍ， ３Ｈ）， １．４９－１．２８ （ｍ， ４Ｈ）， ０．９５－０．８８ （ｍ， １８Ｈ） [Synthesis Example 9: Reductive Amination Reaction-1]

Synthetic intermediate of (3R ^* ,3aR ^* ,6S ^* ,7aS ^* )-2,8-diisobutyl-N-isopentyl-1-oxooctahydro-3a,6-epiiminoisoindole-3-carboxamide (Compound No. 256) Compound 5-5 (10.0 mg) was dissolved in chloroform (1.0 mL), isobutyraldehyde (4.2 μL) and sodium triacetoxyborohydride (20 mg) were sequentially added, and the mixture was stirred at room temperature for 15 hours. A saturated sodium bicarbonate aqueous solution was added to the reaction solution to stop the reaction, and the organic layer was separated using a Phase Separator. The title compound ( 9.3 mg, 79% yield, RT=0.84 min, [M+H]+=378) as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 5.95 (t, J = 5.3 Hz, 1H), 4.00 (s, 1H), 3.50 (dd, J = 13.6, 9.6 Hz, 1H), 3.42 (t, J = 5.3 Hz, 1H), 3.38-3.28 (m, 2H), 2.65 (dd, J = 13.6, 5 .3 Hz, 1H), 2.45 (dd, J = 9.6, 4.5 Hz, 1H), 2.21-2.05 (m, 2H), 1.99-1.84 (m, 4H), 1.67-1.56 (m, 3H), 1.49-1.28 (m, 4H), 0.95-0.88 (m, 18H)

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２，８－ジベンジル－Ｎ－（ナフタレン－１－イルメチル）－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号３０７）の合成
中間体５－１０（５．０ｍｇ）をクロロホルム（１．０ｍＬ）に溶解させ、ベンズアルデヒド（３．６μＬ）、酢酸（１．０μＬ）、トリアセトキシ水素化ホウ素ナトリウム（７．５ｍｇ）を順次添加し、室温にて１７時間撹拌した。反応溶液に飽和炭酸水素ナトリウム水溶液を加えて反応を停止し、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製し、標題化合物（５．２ｍｇ， 収率８４％， ＲＴ＝０．９４分， ［Ｍ＋Ｈ］＋＝５１６）を白色固体として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．９９－７．８７ （ｍ， ２Ｈ）， ７．６３－７．５５ （ｍ， ２Ｈ）， ７．５０－７．４０ （ｍ， ２Ｈ）， ７．３３－７．２７ （ｍ， ５Ｈ）， ７．２５－７．２２ （ｍ， ２Ｈ）， ７．１４－７．０９ （ｍ， ４Ｈ）， ６．１１ （ｔ， Ｊ ＝ ５．５ Ｈｚ， １Ｈ）， ４．９５ （ｄｄ， Ｊ ＝ １４．４， ５．７ Ｈｚ， １Ｈ）， ４．８６ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ４．７９ （ｄｄ， Ｊ ＝ １４．４， ５．７ Ｈｚ， １Ｈ）， ３．９３ （ｓ， １Ｈ）， ３．８２ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ３．５０ （ｄ， Ｊ ＝ １４．０ Ｈｚ， １Ｈ）， ３．３０ （ｔ， Ｊ ＝ ４．５ Ｈｚ， １Ｈ）， ３．２２ （ｄ， Ｊ ＝ １４．０ Ｈｚ， １Ｈ）， ２．５８－２．４８ （ｍ， １Ｈ）， ２．０７－１．９７ （ｍ， ３Ｈ）， １．６４－１．４７ （ｍ， ３Ｈ）． [Synthesis Example 10: Reductive Amination Reaction-2]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2,8-dibenzyl-N-(naphthalen-1-ylmethyl)-1-oxooctahydro-3a,6-epiiminoisoindole-3-carboxamide (compound No. 307) synthetic intermediate 5-10 (5.0 mg) was dissolved in chloroform (1.0 mL), benzaldehyde (3.6 μL), acetic acid (1.0 μL), sodium triacetoxyborohydride (7.5 mg ) were added sequentially and stirred at room temperature for 17 hours. A saturated sodium bicarbonate aqueous solution was added to the reaction solution to stop the reaction, and the organic layer was separated using a Phase Separator. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE 10, eluent: hexane:ethyl acetate 4:1-0:1), and the title compound (5. 2 mg, 84% yield, RT=0.94 min, [M+H]+=516) as a white solid.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.99-7.87 (m, 2H), 7.63-7.55 (m, 2H), 7.50-7.40 (m, 2H ), 7.33-7.27 (m, 5H), 7.25-7.22 (m, 2H), 7.14-7.09 (m, 4H), 6.11 (t, J = 5 .5 Hz, 1H), 4.95 (dd, J = 14.4, 5.7 Hz, 1H), 4.86 (d, J = 15.1 Hz, 1H), 4.79 (dd, J = 14.4, 5.7 Hz, 1H), 3.93 (s, 1H), 3.82 (d, J = 15.1 Hz, 1H), 3.50 (d, J = 14.0 Hz , 1H), 3.30 (t, J = 4.5 Hz, 1H), 3.22 (d, J = 14.0 Hz, 1H), 2.58-2.48 (m, 1H), 2 .07-1.97 (m, 3H), 1.64-1.47 (m, 3H).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－イソペンチル－Ｎ８－イソプロピル－Ｎ３－（ナフタレン－１－イルメチル）－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３，８－ジカルボキサミド（化合物番号３８８）の合成
中間体５－１７（１０．０ｍｇ）をクロロホルム（１．０ｍＬ）に溶解させ、イソプロピルイソシアネート（３．７μＬ）を添加し、室温にて１時間撹拌した。反応溶液を減圧濃縮後、得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製し、標題化合物（１１．２ｍｇ， 収率９１％， ＲＴ＝１．１３分， ［Ｍ＋Ｈ］＋＝４９１）を白色固体として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ８．０８－８．０４ （ｍ， １Ｈ）， ７．９２－７．８９ （ｍ， １Ｈ）， ７．８７－７．８４ （ｍ， １Ｈ）， ７．５６－７．４３ （ｍ， ４Ｈ）， ６．４８ （ｔ， Ｊ ＝ ５．５ Ｈｚ， １Ｈ）， ５．２６ （ｓ， １Ｈ）， ５．１１ （ｄｄ， Ｊ ＝ １４．５， ５．５ Ｈｚ， １Ｈ）， ４．８６ （ｄｄ， Ｊ ＝ １４．５， ５．５ Ｈｚ， １Ｈ）， ４．７２ （ｄ， Ｊ ＝ ７．９ Ｈｚ， １Ｈ）， ３．９０ （ｔ， Ｊ ＝ ５．１ Ｈｚ， １Ｈ）， ３．８４－３．７７ （ｍ， １Ｈ）， ３．６５－３．５５ （ｍ， １Ｈ）， ３．０４－２．９７ （ｍ， １Ｈ）， ２．７８ （ｄｄ， Ｊ ＝ １０．２， ５．１ Ｈｚ， １Ｈ）， ２．０９－１．９８ （ｍ， ２Ｈ）， １．８６ （ｓ， １Ｈ）， １．７０ （ｄｄ， Ｊ ＝ １２．１， １０．２ Ｈｚ， １Ｈ）， １．６１－１．４７ （ｍ， ２Ｈ）， １．３６－１．２８ （ｍ， ３Ｈ）， １．１３ （ｄ， Ｊ ＝ １．９ Ｈｚ， ３Ｈ）， １．１１ （ｄ， Ｊ ＝ １．９ Ｈｚ， ３Ｈ）， ０．８５ （ｄ， Ｊ ＝ １．１ Ｈｚ， ３Ｈ）， ０．８３ （ｄ， Ｊ ＝ １．１ Ｈｚ， ３Ｈ）． [Synthesis Example 11: Urea Synthesis]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-isopentyl-N8-isopropyl-N3-(naphthalen-1-ylmethyl)-1-oxooctahydro-3a,6-epiiminoisoindole-3,8 -Synthetic intermediate 5-17 (10.0 mg) of dicarboxamide (Compound No. 388) was dissolved in chloroform (1.0 mL), isopropyl isocyanate (3.7 µL) was added, and the mixture was stirred at room temperature for 1 hour. After concentrating the reaction solution under reduced pressure, the resulting residue was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE10, eluent: hexane:ethyl acetate 4:1-0:1) to obtain the title compound (11.2 mg). , yield 91%, RT=1.13 min, [M+H]+=491) as a white solid.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 8.08-8.04 (m, 1H), 7.92-7.89 (m, 1H), 7.87-7.84 (m, 1H ), 7.56-7.43 (m, 4H), 6.48 (t, J = 5.5 Hz, 1H), 5.26 (s, 1H), 5.11 (dd, J = 14. 5, 5.5 Hz, 1H), 4.86 (dd, J = 14.5, 5.5 Hz, 1H), 4.72 (d, J = 7.9 Hz, 1H), 3.90 ( t, J = 5.1 Hz, 1H), 3.84-3.77 (m, 1H), 3.65-3.55 (m, 1H), 3.04-2.97 (m, 1H) , 2.78 (dd, J = 10.2, 5.1 Hz, 1H), 2.09-1.98 (m, 2H), 1.86 (s, 1H), 1.70 (dd, J = 12.1, 10.2 Hz, 1H), 1.61-1.47 (m, 2H), 1.36-1.28 (m, 3H), 1.13 (d, J = 1.9 Hz, 3H), 1.11 (d, J = 1.9 Hz, 3H), 0.85 (d, J = 1.1 Hz, 3H), 0.83 (d, J = 1.1 Hz, 3H).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－８－（４－アミノブタノイル）－２－（４－フルオロベンジル）－１－オキソ－Ｎ－フェネチルオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号２４１）の合成
化合物番号２３８（３８．３ｍｇ）をクロロホルム（０．３ｍＬ）に溶解させ、トリフルオロ酢酸（０．３ｍＬ）を添加し、室温にて３時間撹拌した。反応溶液を減圧濃縮後、得られた残渣にクロロホルム及び飽和炭酸水素ナトリウムを加え、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒにて分離した。溶媒を減圧留去後、得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＮＨ３０ ＳＩＺＥ１０， 溶離液：酢酸エチル：メタノール １：０－４：１）にて精製し、標題化合物（２４．１ｍｇ， 収率７５％， ＲＴ＝０．８０分， ［Ｍ＋Ｈ］＋＝４９３）を無色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．３５－７．２３ （ｍ， ４Ｈ）， ７．２０－７．０９ （ｍ， ３Ｈ）， ６．９９－６．９３ （ｍ， ２Ｈ）， ５．９７ （ｓ， １Ｈ）， ５．３３ （ｓ， １Ｈ）， ４．７９ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ４．２９－４．２８ （ｍ， １Ｈ）， ３．９６ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ３．５７－３．４６ （ｍ， ２Ｈ）， ２．９０－２．７６ （ｍ， ３Ｈ）， ２．６７ （ｔｄ， Ｊ ＝ ６．８， １．５ Ｈｚ， ２Ｈ）， ２．３９－２．０７ （ｍ， ３Ｈ）， １．８６－１．７４ （ｍ， ３Ｈ）， １．７０－１．５９ （ｍ， ３Ｈ）． [Synthesis Example 12: Deprotection reaction of Boc group]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-8-(4-aminobutanoyl)-2-(4-fluorobenzyl)-1-oxo-N-phenethyloctahydro-3a,6-epiiminoiso Synthesis of indole-3-carboxamide (Compound No. 241) Compound No. 238 (38.3 mg) was dissolved in chloroform (0.3 mL), trifluoroacetic acid (0.3 mL) was added, and the mixture was stirred at room temperature for 3 hours. . After the reaction solution was concentrated under reduced pressure, chloroform and saturated sodium hydrogencarbonate were added to the resulting residue, and the organic layer was separated using a Phase Separator. After evaporating the solvent under reduced pressure, the resulting residue was purified by silica gel column chromatography (CHROMATOREX Q-PACK NH30 SIZE 10, eluent: ethyl acetate:methanol 1:0-4:1) to obtain the title compound (24.1 mg , yield 75%, RT=0.80 min, [M+H]+=493) as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.35-7.23 (m, 4H), 7.20-7.09 (m, 3H), 6.99-6.93 (m, 2H ), 5.97 (s, 1H), 5.33 (s, 1H), 4.79 (d, J = 15.1 Hz, 1H), 4.29-4.28 (m, 1H), 3 .96 (d, J = 15.1 Hz, 1H), 3.57-3.46 (m, 2H), 2.90-2.76 (m, 3H), 2.67 (td, J = 6 .8, 1.5 Hz, 2H), 2.39-2.07 (m, 3H), 1.86-1.74 (m, 3H), 1.70-1.59 (m, 3H).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－８－［４－（ジメチルアミノ）ブタノイル］－２－（４－フルオロベンジル）－１－オキソ－Ｎ－フェネチルオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号２４３）の合成
化合物番号２４２（１５．７ｍｇ）をクロロホルム（１．０ｍＬ）に溶解させ、３７％ホルムアルデヒド水溶液（１５μＬ）、トリアセトキシ水素化ホウ素ナトリウム（４１ｍｇ）を順次添加し、室温にて３０分間撹拌した。反応溶液に飽和炭酸水素ナトリウム水溶液を加えて反応を停止し、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＮＨ３０ ＳＩＺＥ１０， 溶離液：酢酸エチル：メタノール １：０－４：１）にて精製し、標題化合物（１４．５ｍｇ， 収率８７％， ＲＴ＝０．８１分， ［Ｍ＋Ｈ］＋＝５２１）を無色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．３５－７．２２ （ｍ， ３Ｈ）， ７．２０－７．１７ （ｍ， ２Ｈ）， ７．１４－７．０９ （ｍ， ２Ｈ）， ６．９９－６．９３ （ｍ， ２Ｈ）， ５．９９－５．９６ （ｍ， １Ｈ）， ５．３４ （ｓ， １Ｈ）， ４．７９ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ４．２９ （ｔ， Ｊ ＝ ４．５ Ｈｚ， １Ｈ）， ３．９６ （ｄ， Ｊ ＝ １５．１ Ｈｚ， １Ｈ）， ３．５９－３．４３ （ｍ， ２Ｈ）， ２．９０－２．７５ （ｍ， ３Ｈ）， ２．３９－２．０９ （ｍ， ５Ｈ）， ２．２２ （ｓ， ６Ｈ）， １．８６－１．７８ （ｍ， ３Ｈ）， １．７３－１．４８ （ｍ， ３Ｈ）． [Synthesis Example 13: Reductive amination reaction (dimethylation)]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-8-[4-(dimethylamino)butanoyl]-2-(4-fluorobenzyl)-1-oxo-N-phenethyloctahydro-3a,6-epi Synthesis of iminoisoindole-3-carboxamide (Compound No. 243) Compound No. 242 (15.7 mg) was dissolved in chloroform (1.0 mL), 37% formaldehyde aqueous solution (15 μL), sodium triacetoxyborohydride (41 mg). was added sequentially and stirred at room temperature for 30 minutes. A saturated sodium bicarbonate aqueous solution was added to the reaction solution to stop the reaction, and the organic layer was separated using a Phase Separator. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (CHROMATOREX Q-PACK NH30 SIZE 10, eluent: ethyl acetate:methanol 1:0-4:1) to obtain the title compound (14. 5 mg, 87% yield, RT=0.81 min, [M+H]+=521) as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.35-7.22 (m, 3H), 7.20-7.17 (m, 2H), 7.14-7.09 (m, 2H ), 6.99-6.93 (m, 2H), 5.99-5.96 (m, 1H), 5.34 (s, 1H), 4.79 (d, J = 15.1 Hz, 1H), 4.29 (t, J = 4.5 Hz, 1H), 3.96 (d, J = 15.1 Hz, 1H), 3.59-3.43 (m, 2H), 2. 90-2.75 (m, 3H), 2.39-2.09 (m, 5H), 2.22 (s, 6H), 1.86-1.78 (m, 3H), 1.73- 1.48 (m, 3H).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－ベンジル－８－（４－グアニジノブタノイル）－Ｎ－（ナフタレン－１－イルメチル）－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミドトリフルオロ酢酸塩（化合物番号２４４）の合成
化合物番号２３７（９．９ｍｇ）をテトラヒドロフラン（１．０ｍＬ）に溶解させ、Ｇｏｏｄｍａｎ試薬（１１．４ｍｇ）、トリエチルアミン（８．１μＬ）を順次添加し、室温にて３時間撹拌した。反応溶液を減圧濃縮し、飽和炭酸水素ナトリウム水溶液とクロロホルムを加え、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製した。
上記で得られた化合物をクロロホルム（０．５ｍＬ）に溶解させ、トリフルオロ酢酸（０．５ｍＬ）を添加し、室温にて５時間撹拌した。反応溶液を減圧濃縮することにより標題化合物（１０．３ｍｇ、 収率７９％（２工程）、 ＲＴ＝０．８６分， ［Ｍ＋Ｈ］＋＝５５３）を無色油状物質として得た。 [Synthesis Example 14: Guanidination reaction, deprotection reaction of Boc group]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-benzyl-8-(4-guanidinobutanoyl)-N-(naphthalen-1-ylmethyl)-1-oxooctahydro-3a,6-epiimino Synthesis of isoindole-3-carboxamide trifluoroacetate (Compound No. 244) Compound No. 237 (9.9 mg) was dissolved in tetrahydrofuran (1.0 mL), followed by Goodman's reagent (11.4 mg) and triethylamine (8.1 μL). was added sequentially and stirred at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate solution and chloroform were added, and the organic layer was separated using a Phase Separator. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE10, eluent: hexane:ethyl acetate 4:1-0:1).
The compound obtained above was dissolved in chloroform (0.5 mL), trifluoroacetic acid (0.5 mL) was added, and the mixture was stirred at room temperature for 5 hours. The title compound (10.3 mg, yield 79% (2 steps), RT=0.86 min, [M+H]+=553) was obtained as a colorless oil by concentrating the reaction solution under reduced pressure.

［（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－８－（３－メチルブタノイル）－２－（ナフタレン－１－イルメチル）－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボニル］グリシン（化合物番号４７）の合成
化合物番号４４（３９．７ｍｇ）をクロロホルム（０．５ｍＬ）に溶解させ、トリフルオロ酢酸（０．５ｍＬ）を添加し、室温にて１５時間撹拌した。反応溶液を減圧濃縮後、得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル １：１－０：１）にて精製し、標題化合物（２３．２ｍｇ， 収率６５％， ＲＴ＝０．９７分， ［Ｍ＋Ｈ］＋＝４７８）を白色固体として得た。 [Synthesis Example 15: tert-butyl ester deprotection]

[(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-8-(3-methylbutanoyl)-2-(naphthalen-1-ylmethyl)-1-oxooctahydro-3a,6-epiiminoisoindole- Synthesis of 3-carbonyl]glycine (Compound No. 47) Compound No. 44 (39.7 mg) was dissolved in chloroform (0.5 mL), trifluoroacetic acid (0.5 mL) was added, and the mixture was stirred at room temperature for 15 hours. . After concentrating the reaction solution under reduced pressure, the resulting residue was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE10, eluent: hexane:ethyl acetate 1:1-0:1) to obtain the title compound (23.2 mg). , yield 65%, RT=0.97 min, [M+H]+=478) as a white solid.

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－Ｎ－（２－アミノ－２－オキソエチル）－８－（３－メチルブタノイル）－２－（ナフタレン－１－イルメチル）－１－オキソオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号５０）の合成
化合物番号４７（１９．０ｍｇ）をメタノール（１．０ｍＬ）に溶解させ、７ｍｏｌ／Ｌアンモニア－メタノール溶液（１７．１μＬ）、ＤＭＴ－ＭＭ（３３．０ｍｇ）を順次添加し、室温にて２．５日間撹拌した。反応溶液に飽和炭酸水素ナトリウム水溶液とクロロホルムを加え、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：酢酸エチル：メタノール １：０－４：１）にて精製し、標題化合物（６．１ｍｇ， 収率３２％， ＲＴ＝０．９３分， ［Ｍ＋Ｈ］＋＝４７７）を無色固体として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＤＭＳＯ－Ｄ_６）： δ ８．３８－８．３５ （ｍ， １Ｈ）， ８．０５－８．０２ （ｍ， １Ｈ）， ７．９３－７．９０ （ｍ， １Ｈ）， ７．８５－７．８３ （ｍ， １Ｈ）， ７．５３－７．４９ （ｍ， ２Ｈ）， ７．３９－７．３１ （ｍ， ３Ｈ）， ７．０１ （ｓ， １Ｈ）， ５．５６ （ｓ， １Ｈ）， ５．２０ （ｄ， Ｊ ＝ １５．９ Ｈｚ， １Ｈ）， ４．３６－４．３０ （ｍ， ２Ｈ）， ３．６４ （ｔ， Ｊ ＝ ６．２ Ｈｚ， ２Ｈ）， ２．８６－２．８２ （ｍ， １Ｈ）， ２．１１－２．０３ （ｍ， １Ｈ）， １．９６－１．６８ （ｍ， ６Ｈ）， １．５６－１．５３ （ｍ， ２Ｈ）， ０．７４－０．６７ （ｍ， ６Ｈ）． [Synthesis Example 16: Carboxamide Synthesis]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-N-(2-amino-2-oxoethyl)-8-(3-methylbutanoyl)-2-(naphthalen-1-ylmethyl)-1-oxoocta Synthesis of Hydro-3a,6-epiiminoisoindole-3-carboxamide (Compound No. 50) Compound No. 47 (19.0 mg) was dissolved in methanol (1.0 mL), and 7 mol/L ammonia-methanol solution (17. 1 μL) and DMT-MM (33.0 mg) were sequentially added, and the mixture was stirred at room temperature for 2.5 days. A saturated aqueous sodium hydrogencarbonate solution and chloroform were added to the reaction solution, and the organic layer was separated using a Phase Separator. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE 10, eluent: ethyl acetate:methanol 1:0-4:1), and the title compound (6. 1 mg, 32% yield, RT=0.93 min, [M+H]+=477) as a colorless solid.
¹ H-NMR (300 MHz, DMSO-D ₆ ): δ 8.38-8.35 (m, 1H), 8.05-8.02 (m, 1H), 7.93-7.90 (m , 1H), 7.85-7.83 (m, 1H), 7.53-7.49 (m, 2H), 7.39-7.31 (m, 3H), 7.01 (s, 1H) ), 5.56 (s, 1H), 5.20 (d, J = 15.9 Hz, 1H), 4.36-4.30 (m, 2H), 3.64 (t, J = 6. 2Hz, 2H), 2.86-2.82 (m, 1H), 2.11-2.03 (m, 1H), 1.96-1.68 (m, 6H), 1.56-1 .53 (m, 2H), 0.74-0.67 (m, 6H).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－（４－フルオロベンジル）－８－（４－ヒドロキシベンジル）－１－オキソ－Ｎ－フェネチルオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号３２７）の合成
化合物番号３２４（１３．１ｍｇ）をクロロホルム（０．２５ｍＬ）に溶解させ、トリフルオロ酢酸（０．２５ｍＬ）を添加し、室温にて６時間撹拌した。反応溶液を減圧濃縮後、飽和炭酸水素ナトリウム水溶液とクロロホルムを加え、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル １：１－０：１）にて精製し、標題化合物（１０．５ｍｇ， 収率８９％， ＲＴ＝０．８６分， ［Ｍ＋Ｈ］＋＝５１４）を無色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．４０－７．２６ （ｍ， ３Ｈ）， ７．２３－７．２１ （ｍ， ２Ｈ）， ７．１８－７．１３ （ｍ， ２Ｈ）， ７．０２－６．９９ （ｍ， ２Ｈ）， ６．８６－６．８０ （ｍ， ２Ｈ）， ６．７７－６．７４ （ｍ， ２Ｈ）， ５．９２ （ｔ， Ｊ ＝ ５．５ Ｈｚ， １Ｈ）， ５．１９ （ｓ， １Ｈ）， ４．８８ （ｄ， Ｊ ＝ １５．５ Ｈｚ， １Ｈ）， ３．７９ （ｓ， １Ｈ）， ３．６９－３．５０ （ｍ， ３Ｈ）， ３．３５ （ｄ， Ｊ ＝ １３．６ Ｈｚ， １Ｈ）， ３．２８ （ｔ， Ｊ ＝ ４．５ Ｈｚ， １Ｈ）， ３．１１ （ｄ， Ｊ ＝ １３．６ Ｈｚ， １Ｈ）， ２．８８－２．８４ （ｍ， ２Ｈ）， ２．４７－２．４２ （ｍ， １Ｈ）， １．９９－１．９１ （ｍ， ３Ｈ）， １．４５－１．３９ （ｍ， １Ｈ）， １．３１－１．２１ （ｍ， １Ｈ）． [Synthesis Example 17: tert-butyl ether deprotection reaction-1]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-(4-fluorobenzyl)-8-(4-hydroxybenzyl)-1-oxo-N-phenethyloctahydro-3a,6-epiiminoisoindole Synthesis of -3-carboxamide (Compound No. 327) Compound No. 324 (13.1 mg) was dissolved in chloroform (0.25 mL), trifluoroacetic acid (0.25 mL) was added, and the mixture was stirred at room temperature for 6 hours. After the reaction solution was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate solution and chloroform were added, and the organic layer was separated using a Phase Separator. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE 10, eluent: hexane:ethyl acetate 1:1-0:1), and the title compound (10. 5 mg, 89% yield, RT=0.86 min, [M+H]+=514) as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.40-7.26 (m, 3H), 7.23-7.21 (m, 2H), 7.18-7.13 (m, 2H ), 7.02-6.99 (m, 2H), 6.86-6.80 (m, 2H), 6.77-6.74 (m, 2H), 5.92 (t, J = 5 .5 Hz, 1H), 5.19 (s, 1H), 4.88 (d, J = 15.5 Hz, 1H), 3.79 (s, 1H), 3.69-3.50 (m , 3H), 3.35 (d, J = 13.6 Hz, 1H), 3.28 (t, J = 4.5 Hz, 1H), 3.11 (d, J = 13.6 Hz, 1H ), 2.88-2.84 (m, 2H), 2.47-2.42 (m, 1H), 1.99-1.91 (m, 3H), 1.45-1.39 (m , 1H), 1.31-1.21 (m, 1H).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－（２－ヒドロキシエチル）－１－オキソ－Ｎ－フェネチル－８－（３－フェニルプロパノイル）オクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号１９８）の合成
化合物番号１９７（１１．４ｍｇ）をクロロホルム（０．２５ｍＬ）に溶解させ、トリフルオロ酢酸（０．２５ｍＬ）を添加し、室温にて１９時間撹拌した。反応溶液を減圧濃縮後、メタノール－水（１：１）の混合溶液、炭酸カリウムを順次添加し、室温にてさらに３０分間撹拌した。反応溶液にクロロホルムを加え、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：酢酸エチル：メタノール １：０－４：１）にて精製し、標題化合物（２．８ｍｇ， 収率２８％， ＲＴ＝０．９６分， ［Ｍ＋Ｈ］＋＝４７６）を無色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．３７－７．１７ （ｍ， １０Ｈ）， ６．３１－６．２９ （ｍ， １Ｈ）， ５．７０ （ｓ， １Ｈ）， ４．１７ （ｔ， Ｊ ＝ ４．５ Ｈｚ， １Ｈ）， ３．７１－３．５４ （ｍ， ５Ｈ）， ３．４８－３．４０ （ｍ， １Ｈ）， ３．３２－３．２７ （ｍ， １Ｈ）， ２．９４－２．８６ （ｍ， ４Ｈ）， ２．７８ （ｄｄ， Ｊ ＝ ９．６， ５．１ Ｈｚ， １Ｈ）， ２．６５－２．５０ （ｍ， ２Ｈ）， １．９４－１．９０ （ｍ， １Ｈ）， １．７７－１．７０ （ｍ， １Ｈ）， １．６４－１．５７ （ｍ， １Ｈ）， １．５１－１．４４ （ｍ， ３Ｈ）． [Synthesis Example 18: tert-butyl ether deprotection reaction-1]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-(2-hydroxyethyl)-1-oxo-N-phenethyl-8-(3-phenylpropanoyl)octahydro-3a,6-epiiminoisoindole Synthesis of -3-carboxamide (Compound No. 198) Compound No. 197 (11.4 mg) was dissolved in chloroform (0.25 mL), trifluoroacetic acid (0.25 mL) was added, and the mixture was stirred at room temperature for 19 hours. After concentrating the reaction solution under reduced pressure, a mixed solution of methanol-water (1:1) and potassium carbonate were sequentially added, and the mixture was further stirred at room temperature for 30 minutes. Chloroform was added to the reaction solution, and the organic layer was separated using a Phase Separator. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE10, eluent: ethyl acetate:methanol 1:0-4:1) to obtain the title compound (2. 8 mg, 28% yield, RT=0.96 min, [M+H]+=476) as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.37-7.17 (m, 10H), 6.31-6.29 (m, 1H), 5.70 (s, 1H), 4. 17 (t, J = 4.5 Hz, 1H), 3.71-3.54 (m, 5H), 3.48-3.40 (m, 1H), 3.32-3.27 (m, 1H), 2.94-2.86 (m, 4H), 2.78 (dd, J = 9.6, 5.1 Hz, 1H), 2.65-2.50 (m, 2H), 1 .94-1.90 (m, 1H), 1.77-1.70 (m, 1H), 1.64-1.57 (m, 1H), 1.51-1.44 (m, 3H) .

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－（４－フルオロベンジル）－８－（２－ヒドロキシエチル）－１－オキソ－Ｎ－フェネチルオクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号３４０）の合成
化合物番号３３９（１７．６ｍｇ）をクロロホルム（０．２５ｍＬ）に溶解させ、トリフルオロ酢酸（０．２５ｍＬ）を添加し、室温にて２０時間撹拌した。反応溶液を減圧濃縮後、再度トリフルオロ酢酸（０．３ｍＬ）を添加し、さらに室温で４時間撹拌した。反応溶液を減圧濃縮後、飽和炭酸水素ナトリウム水溶液とクロロホルムを加え、有機層をＰｈａｓｅ Ｓｅｐａｒａｔｏｒを用いて分離した。溶媒を減圧留去することにより得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：酢酸エチル：メタノール １：０－４：１）にて精製し、標題化合物（８．７ｍｇ， 収率６２％， ＲＴ＝０．８１分， ［Ｍ＋Ｈ］＋＝４５２）を白色固体として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３）： δ ７．３９－７．２５ （ｍ， ３Ｈ）， ７．２１－７．１４ （ｍ， ４Ｈ）， ７．０６－６．９９ （ｍ， ２Ｈ）， ５．８７ （ｔ， Ｊ ＝ ５．５ Ｈｚ， １Ｈ）， ４．７９ （ｄ， Ｊ ＝ １４．７ Ｈｚ， １Ｈ）， ３．７６ （ｄ， Ｊ ＝ １４．７ Ｈｚ， １Ｈ）， ３．７３ （ｓ， １Ｈ）， ３．６８－３．５７ （ｍ， １Ｈ）， ３．５１－３．３８ （ｍ， ３Ｈ）， ３．３４－３．２７ （ｍ， １Ｈ）， ２．８２ （ｔ， Ｊ ＝ ７．０ Ｈｚ， ２Ｈ）， ２．４４－２．３３ （ｍ， ２Ｈ）， ２．２７－２．２０ （ｍ， １Ｈ）， １．９９－１．８７ （ｍ， ２Ｈ）， １．７５－１．６１ （ｍ， ３Ｈ）， １．４７－１．３９ （ｍ， １Ｈ）， １．３１－１．１６ （ｍ， ２Ｈ）． [Synthesis Example 19: Deprotection reaction of TBS group]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-(4-fluorobenzyl)-8-(2-hydroxyethyl)-1-oxo-N-phenethyloctahydro-3a,6-epiiminoisoindole Synthesis of -3-carboxamide (Compound No. 340) Compound No. 339 (17.6 mg) was dissolved in chloroform (0.25 mL), trifluoroacetic acid (0.25 mL) was added, and the mixture was stirred at room temperature for 20 hours. After the reaction solution was concentrated under reduced pressure, trifluoroacetic acid (0.3 mL) was added again, and the mixture was stirred at room temperature for 4 hours. After the reaction solution was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate solution and chloroform were added, and the organic layer was separated using a Phase Separator. The residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE10, eluent: ethyl acetate:methanol 1:0-4:1), and the title compound (8. 7 mg, 62% yield, RT=0.81 min, [M+H]+=452) as a white solid.
¹ H-NMR (300 MHz, CDCl ₃ ): δ 7.39-7.25 (m, 3H), 7.21-7.14 (m, 4H), 7.06-6.99 (m, 2H ), 5.87 (t, J = 5.5 Hz, 1H), 4.79 (d, J = 14.7 Hz, 1H), 3.76 (d, J = 14.7 Hz, 1H), 3.73 (s, 1H), 3.68-3.57 (m, 1H), 3.51-3.38 (m, 3H), 3.34-3.27 (m, 1H), 2. 82 (t, J = 7.0 Hz, 2H), 2.44-2.33 (m, 2H), 2.27-2.20 (m, 1H), 1.99-1.87 (m, 2H), 1.75-1.61 (m, 3H), 1.47-1.39 (m, 1H), 1.31-1.16 (m, 2H).

（３Ｒ^＊，３ａＲ^＊，６Ｓ^＊，７ａＳ^＊）－２－イソペンチル－１－オキソ－Ｎ－フェネチル－８－（３－フェニルプロパノイル）オクタヒドロ－３ａ，６－エピイミノイソインドール－３－カルボキサミド（化合物番号１９２）の合成
化合物番号１９３（３８．４ｍｇ）をメタノール（１．５ｍＬ）に溶解させ、パラジウム／炭素（Ｐｄ１０％）（４．１ｍｇ）を加えた後、水素雰囲気下、室温にて２時間撹拌した。反応溶液をセライトろ過した後、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（ＣＨＲＯＭＡＴＯＲＥＸ Ｑ－ＰＡＣＫ ＳＩ３０ ＳＩＺＥ１０， 溶離液：ヘキサン：酢酸エチル ４：１－０：１）にて精製することにより標題化合物（３０．３ｍｇ， 収率７８％， ＲＴ＝１．１５分，［Ｍ＋Ｈ］＋＝５０２）を無色油状物質として得た。
^１Ｈ－ＮＭＲ （３００ ＭＨｚ， ＣＤＣｌ_３） δ ７．３６－７．１８ （ｍ， １０Ｈ）， ６．１３ （ｔ， Ｊ ＝ ６．０ Ｈｚ， １Ｈ）， ５．６３ （ｓ， １Ｈ）， ４．１５ （ｔ， Ｊ ＝ ４．２ Ｈｚ， １Ｈ）， ３．６９－３．５１ （ｍ， ３Ｈ）， ２．９５－２．８７ （ｍ， ５Ｈ）， ２．７５ （ｄｄ， Ｊ ＝ ９．６， ５．５ Ｈｚ， １Ｈ）， ２．６２－２．４８ （ｍ， ２Ｈ）， ２．０１ （ｓ， １Ｈ）， １．７８－１．６８ （ｍ， ２Ｈ）， １．５６－１．４６ （ｍ， ４Ｈ）， １．３７－１．２９ （ｍ， ２Ｈ）， ０．９１ （ｄ， Ｊ ＝ ６．８ Ｈｚ， ６Ｈ）． [Synthesis Example 20: Catalytic hydrogen reduction]

(3R ^* , 3aR ^* , 6S ^* , 7aS ^* )-2-isopentyl-1-oxo-N-phenethyl-8-(3-phenylpropanoyl)octahydro-3a,6-epiiminoisoindole-3-carboxamide ( Synthesis of Compound No. 192) Compound No. 193 (38.4 mg) was dissolved in methanol (1.5 mL), and palladium/carbon (Pd 10%) (4.1 mg) was added. Stirred for an hour. After the reaction solution was filtered through celite, the solvent was distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography (CHROMATOREX Q-PACK SI30 SIZE10, eluent: hexane:ethyl acetate 4:1-0:1) to give the title compound (30.3 mg, yield 78%, RT=1.15 min, [M+H]+=502) was obtained as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 7.36-7.18 (m, 10H), 6.13 (t, J = 6.0 Hz, 1H), 5.63 (s, 1H), 4.15 (t, J = 4.2 Hz, 1H), 3.69-3.51 (m, 3H), 2.95-2.87 (m, 5H), 2.75 (dd, J = 9.6, 5.5 Hz, 1H), 2.62-2.48 (m, 2H), 2.01 (s, 1H), 1.78-1.68 (m, 2H), 1.56 -1.46 (m, 4H), 1.37-1.29 (m, 2H), 0.91 (d, J = 6.8 Hz, 6H).

The compounds shown in the table below were synthesized according to the methods of Synthesis Examples 7 to 20 using corresponding starting materials. wherein the backbone is selected from either Formula I or Formula II, and R ₁ , R ₂ and R ₃ are each selected from the corresponding table.

(Example 2: Confirmation of biological activity: measurement of cell proliferation using K-562 cells)
Human chronic myeloid leukemia-derived K-562 cells (RIKEN BioResource Research Center, RCB1897) were added to RPMI-1640 medium (Nacalai Tesque, 30264- 85) was subcultured (twice/week) under conditions of 37° C., 5% CO ₂ -95% air.

3×10 ³ K-562 cells per well were seeded in 96-well plates. A test compound was added and cultured for 3 days. Thereafter, the cell proliferation ability of each well was measured by the WST method (Dojindo Laboratories, Cell Counting Kit-8), and the inhibition rate of each test compound relative to the control (wells containing no test compound) was calculated.

The inhibitory activities of the compounds synthesized in the above Examples are summarized in the table below. It was classified as A if the inhibition rate at 100 μM was 75% or more, B if less than 75% and 50% or more, C if less than 50% and 25% or more, and D if less than 25%.

From the above, it is understood that the compounds of the present disclosure have the ability to kill leukemia.

(Example 3: Formulation example)
The compounds of this disclosure may be provided in any suitable dosage form. Examples are shown below.
Examples include tablets, capsules, powders, granules, liquids, suspensions, injections, patches, poultices and the like. In addition, these formulations can be produced by a known method including using additives that are commonly used as pharmaceutical additives and appropriately mixing them.

(Note)
While the present disclosure has been illustrated using the preferred embodiments thereof, it is understood that the present disclosure is to be construed in scope only by the claims. The patents, patent applications and other publications cited herein are hereby incorporated by reference in their entirety to the same extent as if the content itself were specifically set forth herein. It is understood.

The present disclosure is useful in the pharmaceutical industry.

Claims (28)

Formula I:

A compound represented by or an enantiomer thereof or a salt thereof or a solvate thereof, wherein
_R1 is
optionally substituted alkyl,
optionally substituted alkenyl,
optionally substituted alkynyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl,
optionally substituted heteroaryl, or optionally substituted carbonyl,
R ₂ and R ₃ are each independently
hydrogen,
optionally substituted alkyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl, or optionally substituted heteroaryl,
A compound or its enantiomers or their salts or their solvates. Formula II:

A compound represented by or an enantiomer thereof or a salt thereof or a solvate thereof, wherein
_R1 is
optionally substituted alkyl,
optionally substituted alkenyl,
optionally substituted alkynyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl,
optionally substituted heteroaryl, or optionally substituted carbonyl,
R ₂ and R ₃ are each independently
hydrogen,
optionally substituted alkyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl, or optionally substituted heteroaryl,
A compound or its enantiomers or their salts or their solvates. The alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl and carbonyl of R ₁ are each independently selected from Substituent Group I and are the same or different from 1 to the maximum substitutable number. optionally substituted with substituents,
3. A compound according to claim 1 or 2, an enantiomer thereof, a salt thereof, or a solvate thereof. Each of said alkyl, cycloalkyl, heterocycloalkyl, aryl and heteroaryl of R ₂ and R ₃ is independently required from 1 to the maximum substitutable number of the same or different substituents selected from Substituent Group I. are replaced according to the
3. A compound according to claim 1 or 2, an enantiomer thereof, a salt thereof, or a solvate thereof. _R1 is
optionally substituted alkyl,
optionally substituted cycloalkylalkyl,
optionally substituted heterocycloalkylalkyl,
optionally substituted arylalkyl,
optionally substituted heteroarylalkyl,
optionally substituted carboxyalkyl,
optionally substituted carbamoylalkyl,
optionally substituted aminoalkyl,
optionally substituted alkenyl,
optionally substituted alkynyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl,
optionally substituted heteroaryl,
optionally substituted carbonyl,
optionally substituted alkylcarbonyl,
optionally substituted alkenylcarbonyl,
optionally substituted cycloalkylcarbonyl,
optionally substituted arylcarbonyl,
optionally substituted carboxy, or optionally substituted carbamoyl,
wherein the above groups for R ₁ are optionally substituted with 1 to the maximum substitutable number of the same or different substituents selected from Substituent Group II,
A compound according to any one of claims 1 to 4 or an enantiomer thereof or a salt or solvate thereof. R ₂ and R ₃ are each independently
optionally substituted alkyl,
optionally substituted cycloalkylalkyl,
optionally substituted arylalkyl,
optionally substituted heteroarylalkyl,
optionally substituted carbonylalkyl,
optionally substituted carboxyalkyl,
optionally substituted carbamoylalkyl,
optionally substituted aminoalkyl,
optionally substituted cycloalkyl,
optionally substituted heterocycloalkyl,
optionally substituted aryl, or optionally substituted heteroaryl,
wherein the above groups for R ₂ and R ₃ are optionally substituted with the same or different substituents from 1 to the maximum substitutable number selected from Substituent Group II,
A compound according to any one of claims 1 to 4 or an enantiomer thereof or a salt or solvate thereof. _R1 is
alkyl,
one up to maximum substitution selected from the group consisting of cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino and substituted amino alkyl substituted with up to the possible number of identical or different substituents;
alkenyl,
alkynyl,
cycloalkyl,
heterocycloalkyl,
Aryl,
aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
heteroaryl,
carbonyl substituted with a substituent selected from the group consisting of cycloalkyl, alkenyl, and aryl;
alkylcarbonyl,
halogen, hydroxy, cycloalkyl, aryl, substituted aryl, heteroaryl, carboxy, substituted carboxy, carbamoyl, amino, substituted amino, guanidino and substituted oxy, identical or different from one to the maximum possible number of substitutions alkylcarbonyl substituted with a substituent,
carboxy substituted with a substituent selected from the group consisting of alkyl and substituted alkyl, or the same from 1 to the maximum number of possible substitutions selected from the group consisting of alkyl, substituted alkyl, substituted cycloalkyl, and aryl or carbamoyl substituted with different substituents,
Here, substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently selected from Substituent Group III, and having identical or different substituents,
A compound according to any one of claims 1 to 6 or an enantiomer thereof or a salt or solvate thereof. _R2 is
alkyl,
cycloalkyl, aryl, substituted aryl, heteroaryl, substituted carbonyl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy, from one to the maximum possible number of substitutions alkyl substituted with the same or different substituents of
cycloalkyl,
heterocycloalkyl,
Aryl,
aryl or heteroaryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
Here, substituted aryl, substituted carbonyl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently the same or different substituents selected from Substituent Group III up to the maximum substitutable number. have
A compound according to any one of claims 1 to 7 or an enantiomer thereof or a salt or solvate thereof. _R3 is
alkyl,
cycloalkyl, aryl, substituted aryl, heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy, identical or alkyl substituted with different substituents,
cycloalkyl,
heterocycloalkyl,
aryl or aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
wherein substituted aryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy each independently have the same or different substituents selected from Substituent Group III up to the maximum possible number of substituents;
A compound according to any one of claims 1 to 8 or an enantiomer thereof or a salt or solvate thereof. _R1 is
alkyl,
one up to maximum substitution selected from the group consisting of cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino and substituted amino alkyl substituted with up to the possible number of identical or different substituents;
alkenyl,
alkynyl,
cycloalkyl,
heterocycloalkyl,
Aryl,
aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
heteroaryl,
carbonyl substituted with a substituent selected from the group consisting of cycloalkyl, alkenyl, and aryl;
alkylcarbonyl,
halogen, hydroxy, cycloalkyl, aryl, substituted aryl, heteroaryl, carboxy, substituted carboxy, carbamoyl, amino, substituted amino, guanidino and substituted oxy, identical or different from one to the maximum possible number of substitutions alkylcarbonyl substituted with a substituent,
carboxy substituted with a substituent selected from the group consisting of alkyl and substituted alkyl; carbamoyl substituted with different substituents,
wherein substituted heterocycloalkyl, substituted aryl, substituted heteroaryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently halogen, alkyl, hydroxy, alkoxy, aryl, tert-butoxycarbonyl groups, and having the same or different substituents from 1 to the maximum substitutable number selected from tert-butyldimethylsilyl groups,
A compound according to any one of claims 1 to 9 or an enantiomer thereof or a salt or solvate thereof. _R2 is
alkyl,
cycloalkyl, aryl, substituted aryl, heteroaryl, substituted carbonyl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy, from one to the maximum possible number of substitutions alkyl substituted with the same or different substituents of
cycloalkyl,
heterocycloalkylaryl,
aryl or heteroaryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
wherein substituted aryl, substituted carbonyl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently identical from one to the maximum possible number of substitutions selected from halogen, alkyl, heterocyclyl, hydroxy and alkoxy; or with different substituents,
A compound according to any one of claims 1 to 9 or an enantiomer thereof or a salt or solvate thereof. _R3 is
alkyl,
cycloalkyl, aryl, substituted aryl, heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy, identical or alkyl substituted with different substituents,
cycloalkyl,
heterocycloalkyl,
aryl or aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
wherein substituted aryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy each independently represent from one to the maximum possible number of the same or different substituents selected from halogen, alkyl, hydroxy and alkoxy; have
A compound according to any one of claims 1 to 9 or an enantiomer thereof or a salt or solvate thereof. _R1 is
C _1-6 alkyl,
C _3-10 cycloalkyl, C _3-10 heterocycloalkyl, substituted C _3-10 heterocycloalkyl, C _3-10 aryl, substituted C _3-10 aryl, C _3-10 heteroaryl, substituted C _3-10 hetero C _1-6 alkyl substituted with the same or different substituents from 1 to the maximum possible number of substituents selected from the group consisting of aryl, carboxy, substituted carboxy, carbamoyl, amino and substituted amino;
C _2-6 alkenyl,
C _2-6 alkynyl,
C _3-10 cycloalkyl,
C _3-10 heterocycloalkyl,
C _3-10 aryl,
C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
C _3-10 heteroaryl,
carbonyl substituted with a substituent selected from the group consisting of C _3-10 cycloalkyl, C _2-6 alkenyl, and C _3-10 aryl;
C _1-6 alkylcarbonyl,
the group consisting of halogen, hydroxy, C _3-10 cycloalkyl, C _3-10 aryl, substituted C _3-10 aryl, C _3-10 heteroaryl, carboxy, substituted carboxy, carbamoyl, amino, substituted amino, guanidino and substituted oxy C _1-6 alkylcarbonyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from
C _1-6 alkyl, and carboxy substituted with a substituent selected from the group consisting of C _1-6 alkyl, or C _1-6 alkyl, substituted C _1-6 alkyl, C _3-10 cycloalkyl, and C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents,
wherein substituted C _3-10 heterocycloalkyl, substituted C _3-10 aryl, substituted C _3-10 heteroaryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently halogen, C _{1- 6} alkyl, hydroxy, C _1-6 alkoxy, C _3-10 aryl, tert-butoxycarbonyl group, and tert-butyldimethylsilyl group having the same or different substituents from 1 to the maximum possible number of substituents ,
A compound according to any one of claims 1 to 12 or an enantiomer thereof or a salt or solvate thereof. _R2 is
C _1-6 alkyl,
C _3-10 cycloalkyl, C _3-10 aryl, substituted C _3-10 aryl, C _3-10 heteroaryl, substituted carbonyl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted C _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of oxy,
C _3-10 cycloalkyl,
C _3-10 heterocycloalkylC _3-10 aryl,
C _3-10 aryl or C _3-10 heteroaryl substituted with from 1 to the maximum possible number of substituents by halogen with the same or different substituents;
wherein substituted C _3-10 aryl, substituted carbonyl, substituted carboxy, substituted carbamoyl, substituted amino and substituted oxy are each independently one selected from halogen, alkyl, heterocyclyl, hydroxy and C _1-6 alkoxy with the same or different substituents from to the maximum possible number of substituents,
A compound according to any one of claims 1 to 12 or an enantiomer thereof or a salt or solvate thereof. _R3 is
C _1-6 alkyl,
consisting of C _3-10 cycloalkyl, C _3-10 aryl, substituted C _3-10 aryl, C _3-10 heteroaryl, carboxy, substituted carboxy, carbamoyl, substituted carbamoyl, amino, substituted amino, guanidino, hydroxy and substituted oxy C _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group,
C _3-10 cycloalkyl,
C _3-10 heterocycloalkyl,
C _3-10 aryl, or C _3-10 aryl substituted with from 1 to the maximum possible number of substituents with the same or different substituents with halogen;
wherein substituted C _3-10 aryl, substituted C _3-10 heteroaryl, substituted carboxy, substituted carbamoyl, substituted amino, and substituted oxy are each independently halogen, C _1-6 alkyl, hydroxy and C _1-6 having the same or different substituents from 1 to the maximum possible number of substituents selected from alkoxy;
A compound according to any one of claims 1 to 12 or an enantiomer thereof or a salt or solvate thereof. _R1 is
C _1-6 alkyl,
C _3-10 cycloalkyl C _1-6 alkyl,
C _3-10 heterocycloalkyl C _1-6 alkyl,
C _3-10 heterocycloalkylC _1-6 alkyl substituted with from 1 to the maximum possible number of the same or different substituents selected from the group consisting of C _1-6 alkyl and tert-butoxycarbonyl group,
C _3-10 aryl C _1-6 alkyl,
C _3-10 arylC 1-6 substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of C _1-6 alkyl, halogen, hydroxy _{and C 1-6 alkoxy} alkyl,
C _3-10 heteroaryl C _1-6 alkyl,
C _3-10 heteroaryl C _1-6 alkyl substituted from one to the maximum possible number of substitutions with a tert-butoxycarbonyl group,
carboxyC _1-6 alkyl,
carboxyC _1-6 alkyl substituted with C _1-6 alkyl,
carbamoyl C _1-6 alkyl,
amino C _1-6 alkyl,
aminoC _1-6 alkyl substituted with from 1 to the maximum possible number of substituents on C _1-6 alkyl with the same or different substituents;
C _2-6 alkenyl,
C _2-6 alkynyl,
C _3-10 cycloalkyl,
C _3-10 heterocycloalkyl,
C _3-10 aryl,
C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents with halogen;
C _3-10 heteroaryl,
carbonyl substituted with a substituent selected from the group consisting of C _3-10 cycloalkyl, C _2-6 alkenyl, and C _3-10 aryl;
C _1-6 alkylcarbonyl,
selected from the group consisting of halogen, hydroxy, C _1-6 alkoxy, C _3-10 cycloalkyl, C _3-10 heteroaryl, carboxy, C _1-6 alkylcarboxy, carbamoyl, amino, tert-butoxycarbonylamino and guanidino C _1-6 alkylcarbonyl substituted with the same or different substituents from 1 to the maximum substitutable number of
C _3-10 aryl C _1-6 alkylcarbonyl,
C _3-10 arylC _1-6 alkylcarbonyl substituted with from 1 to the maximum substitutable number of the same or different substituents selected from the group consisting of halogen, hydroxy and C _1-6 alkoxy;
carboxy substituted with a substituent selected from the group consisting of C _1-6 alkyl, and C _3-10 arylC _1-6 alkyl, or C _1-6 alkyl, C _3-10 arylC _1-6 alkyl , C _3-10 cycloalkyl, and C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents,
A compound according to any one of claims 1 to 15 or an enantiomer thereof or a salt or solvate thereof. _R1 is
carbonyl substituted with a substituent selected from the group consisting of C _3-10 cycloalkyl, C _2-6 alkenyl, and C _3-10 aryl;
C _1-6 alkylcarbonyl,
selected from the group consisting of halogen, hydroxy, C _1-6 alkoxy, C _3-10 cycloalkyl, C _3-10 heteroaryl, carboxy, C _1-6 alkylcarboxy, carbamoyl, amino, tert-butoxycarbonylamino and guanidino C _1-6 alkylcarbonyl substituted with the same or different substituents from 1 to the maximum substitutable number of
C _3-10 aryl C _1-6 alkylcarbonyl,
C _3-10 arylC _1-6 alkylcarbonyl substituted with from 1 to the maximum substitutable number of the same or different substituents selected from the group consisting of halogen, hydroxy and C _1-6 alkoxy;
carboxy substituted with a substituent selected from the group consisting of C _1-6 alkyl, and C _3-10 arylC _1-6 alkyl, or C _1-6 alkyl, C _3-10 arylC _1-6 alkyl , C _3-10 cycloalkyl, and C _3-10 aryl substituted with the same or different substituents from 1 to the maximum possible number of substituents,
A compound according to any one of claims 1 to 16 or an enantiomer thereof or a salt or solvate thereof. _R2 is
C _1-6 alkyl,
substituted with from 1 to the maximum possible number of the same or different substituents selected from the group consisting of C _3-10 cycloalkyl, C _3-10 heteroaryl, pyrrolidinecarbonyl, guanidino, hydroxy and C _1-6 alkoxy; C _1-6 alkyl,
C _3-10 aryl C _1-6 alkyl,
C _3-10 arylC _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of halogen, hydroxy and C _1-6 alkoxy;
carboxyC _1-6 alkyl,
carboxyC _1-6 alkyl substituted with C _1-6 alkyl,
carbamoyl C _1-6 alkyl,
carbamoylC _1-6 alkyl substituted with from 1 to the maximum possible number of substituents on C _1-6 alkyl with the same or different substituents;
amino C _1-6 alkyl,
aminoC _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of C _1-6 alkyl and tert-butoxycarbonyl;
C _3-10 cycloalkyl,
C _3-10 heterocycloalkylC _3-10 aryl,
C _3-10 aryl or C _3-10 heteroaryl substituted with from 1 to the maximum possible number of substituents with the same or different substituents with halogen;
A compound according to any one of claims 1 to 15 or an enantiomer thereof or a salt or solvate thereof. _R3 is
C _1-6 alkyl,
C substituted with one to the maximum substitutable number of the same or different substituents selected from the group consisting of C _3-10 cycloalkyl, C _3-10 heteroaryl, guanidino, hydroxy and C _1-6 alkoxy; _1-6 alkyl,
C _3-10 aryl C _1-6 alkyl,
C _3-10 arylC _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of halogen, hydroxy and C _1-6 alkoxy;
carboxyC _1-6 alkyl,
carboxyC _1-6 alkyl substituted with C _1-6 alkyl,
carbamoyl C _1-6 alkyl,
carbamoylC _1-6 alkyl substituted with from 1 to the maximum possible number of substituents on C _1-6 alkyl with the same or different substituents;
amino C _1-6 alkyl,
aminoC _1-6 alkyl substituted with the same or different substituents from 1 to the maximum substitutable number selected from the group consisting of C _1-6 alkyl and tert-butoxycarbonyl;
C _3-10 cycloalkyl,
C _3-10 heterocycloalkyl C _3-10 aryl, or C _3-10 aryl substituted with from 1 to the maximum possible number of substituents with the same or different substituents with halogen;
A compound according to any one of claims 1 to 15 or an enantiomer thereof or a salt or solvate thereof. R ₁ is the following table,

A compound or enantiomer thereof or a salt or solvate thereof according to any one of claims 1 to 19, selected from: R ₂ is represented in the table below,

A compound or enantiomer thereof or a salt or solvate thereof according to any one of claims 1 to 19, selected from: R ₃ is the following table,

A compound or enantiomer thereof or a salt or solvate thereof according to any one of claims 1 to 19, selected from: An anticancer agent comprising the compound according to any one of claims 1 to 22 or a pharmaceutically acceptable salt thereof. A medicament containing the compound according to any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof. 25. The medicament according to claim 24, which is a preventive or therapeutic agent for cancer. A pharmaceutical composition comprising a compound according to any one of claims 1 to 22 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. A pharmaceutical composition for preventing or treating cancer, comprising the compound according to any one of claims 1 to 22 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier. 28. The medicament according to claim 25 or the pharmaceutical composition according to claim 27, wherein said cancer comprises leukemia.