JP2010138072A - New fused pyrrole derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new fused pyrrole derivative useful as a medicine. <P>SOLUTION: A compound is represented by general formula (1) (wherein R<SP>1</SP>is substituted alkyl or the like; R<SP>2</SP>is a hydrogen atom or the like; [-W<SP>4</SP>=W<SP>5</SP>-W<SP>6</SP>=W<SP>7</SP>-] is the formula: -CR<SP>4</SP>=CR<SP>5</SP>-CR<SP>6</SP>=CR<SP>7</SP>- [wherein R<SP>4</SP>, R<SP>5</SP>, R<SP>6</SP>and R<SP>7</SP>are each independently the formula: -E-A or the like; E is a single bond or the like; A is a hydrogen atom or the like]; R<SP>8</SP>is a hydrogen atom or the like; R<SP>9</SP>is alkyl substituted with a halogen atom or the like; and R<SP>10</SP>is a hydrogen atom or the like), a prodrug or pharmacologically acceptable salts thereof. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a novel condensed pyrrole derivative useful as a medicine. More specifically, the present invention relates to a novel condensed pyrrole derivative useful as a glucocorticoid receptor function modulator (modulator), that is, an anti-inflammatory agent or an antidiabetic agent.

  Steroidal anti-inflammatory drugs have strong anti-inflammatory and immunosuppressive effects, and are used for inflammatory diseases and autoimmune diseases based on excessive immune responses. These are known to bind to a glucocorticoid receptor (hereinafter abbreviated as GR) known as an intranuclear receptor to exert an anti-inflammatory action and an immunomodulatory action. In the old days, it was a steroid that was highly effective against rheumatism, one of the intractable inflammatory diseases. It is also clear that it shows strong side effects such as. Therefore, in recent years, a novel GR-binding compound (GR ligand) has been desired as a new anti-inflammatory therapeutic agent with reduced side effects while maintaining the same anti-inflammatory effect as steroids.

With regard to the anti-inflammatory action exhibited by steroidal anti-inflammatory agents and the metabolic actions such as sugar metabolism and bone metabolism, the following molecular mechanisms are becoming clear due to recent research progress.
GR normally stays in the cytoplasm, but once the steroid, a GR ligand, is bound, GR moves from the cytoplasm into the nucleus and regulates gene transcription. At that time, GR acts on an inflammatory transcription factor such as AP1 or NF-κB or an enzyme involved in an inflammatory reaction and suppresses their activity, thereby exhibiting an anti-inflammatory effect. On the other hand, the action mechanism that GR exerts metabolic actions such as sugar metabolism and bone metabolism is as follows: GR forms a homodimer, and a glucocorticoid responsive element (GRE) in the vicinity of the target gene It is thought to regulate transcription by directly binding to a called gene sequence.

  Based on the above findings, attempts have been reported to search for compounds that have reduced metabolic effects while maintaining anti-inflammatory effects. In particular, when focusing on the reduction of side effects in steroidal anti-inflammatory agents, steroidal anti-inflammatory agents that have been used in the past have strong agonistic effects on GRE-mediated transcriptional regulation, and this agonistic action is a metabolic action. It is considered the body. Therefore, it is thought that by searching for a compound that exerts a weaker agonist effect than conventional steroidal anti-inflammatory agents, that is, a partial agonist of GR, a compound with reduced side effects can be found. Inflammatory compounds have also been reported (see Patent Document 1).

  On the other hand, in a state where blood cortisol concentration is high or GR can be excessively activated, such as Cushing's syndrome, it is useful to suppress excessive activation of GR. In addition, compounds that suppress the action of glucocorticoids via GR are thought to normalize those abnormal states in a state of reduced immune function, depression, or increased glucose metabolism, and GR antagonists have been reported. (See Patent Document 2). In particular, diabetes has increased gluconeogenesis, and excessive production of glucose by the liver is observed. It is known that GR increases the expression of various transaminases that convert amino acids into glucose precursors, glucose-6 phosphatase, phosphoenolpyruvate carboxykinase (PEPCK), and the like, and it is known that hyperglycemia occurs. Is expected to be a therapeutic drug for diabetes.

  Nuclear receptors with high homology with GR include nuclear receptors such as AR (Androgen receptor), MR (Mineralocorticoid receptor), PR (Progesterone receptor). Widely known. In any nuclear receptor, low molecular ligands have been extensively studied. Among them, it has been reported that a compound having an indole skeleton has an action on a nuclear receptor (see Patent Document 3).

In addition, examples of the compound having a condensed pyrrole skeleton include indole derivatives, and synthetic methods thereof have been disclosed so far (Non-patent Document 1).

International Publication No. 2004/058733 Pamphlet US Patent Application Publication No. 2004/0235810 International Publication No. 2004/067529 Pamphlet

Bulletin of the Chemical Society of Japan, 75 (12), 2637-2645, 2002.

The problem to be solved by the present invention is to provide a therapeutic or prophylactic agent for all pathological conditions involving GR, specifically, diseases such as inflammation. Specifically, the object is to provide a compound that exhibits partial agonistic properties with respect to GR as a non-steroidal anti-inflammatory drug with reduced side effects compared to steroidal anti-inflammatory drugs.

As a result of intensive studies, the present inventors have found that the following compounds having a condensed pyrrole skeleton, prodrugs thereof, or pharmaceutically acceptable salts thereof function as a GR modulator, and the present invention has been completed. I came to let you.

That is, the present invention
[1] Formula (1):

［式中、Ｒ¹は、置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、置換もしくは無置換のアルコキシ基、置換もしくは無置換のアルカノイル基、置換もしくは無置換のアルコキシカルボニル基、置換もしくは無置換のアルキルスルホニル基、置換もしくは無置換のシクロアルキルオキシ基、置換もしくは無置換のシクロアルキルカルボニル基、置換もしくは無置換のシクロアルキルオキシカルボニル基、置換もしくは無置換のシクロアルキルスルホニル基、置換もしくは無置換のアリールオキシ基、置換もしくは無置換のアロイル基、置換もしくは無置換のアリールオキシカルボニル基、置換もしくは無置換のアリールスルホニル基、置換もしくは無置換のヘテロアリールオキシ基、置換もしくは無置換のヘテロアリールカルボニル基、置換もしくは無置換のヘテロアリールオキシカルボニル基、置換もしくは無置換のヘテロアリールスルホニル基、置換もしくは無置換のアラルキルオキシ基、置換もしくは無置換のアラルキルカルボニル基、置換もしくは無置換のアラルキルオキシカルボニル基、置換もしくは無置換のアラルキルスルホニル基、置換もしくは無置換のヘテロアラルキルオキシ基、置換もしくは無置換のヘテロアラルキルカルボニル基、置換もしくは無置換のヘテロアラルキルオキシカルボニル基、置換もしくは無置換のヘテロアラルキルスルホニル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環カルボニル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環スルホニル基、置換もしくは無置換のカルバモイル基、又は置換もしくは無置換のスルファモイル基を表し、
Ｒ²は、水素原子、ハロゲン原子、カルボキシル基、置換もしくは無置換のアルキル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、置換もしくは無置換のアルカノイル基、置換もしくは無置換のシクロアルキルカルボニル基、置換もしくは無置換のアルコキシカルボニル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基、又は置換もしくは無置換のアルキル基で置換されてもよいカルバモイル基を表し、
−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−は、以下の式（ａ）〜（ｈ）：
（ａ） −ＣＲ⁴＝ＣＲ⁵−ＣＲ⁶＝ＣＲ⁷−；
（ｂ） −Ｎ＝ＣＲ⁵−ＣＲ⁶＝ＣＲ⁷−；
（ｃ） −ＣＲ⁴＝Ｎ−ＣＲ⁶＝ＣＲ⁷−；
（ｄ） −ＣＲ⁴＝ＣＲ⁵−Ｎ＝ＣＲ⁷−；
（ｅ） −ＣＲ⁴＝ＣＲ⁵−ＣＲ⁶＝Ｎ−；
（ｆ） −Ｎ＝ＣＲ⁵−Ｎ＝ＣＲ⁷−；
（ｇ） −ＣＲ⁴＝Ｎ−ＣＲ⁶＝Ｎ−；
（ｈ） −ＣＲ⁴＝Ｎ−Ｎ＝ＣＲ⁷−
〔式中、Ｒ⁴、Ｒ⁵、Ｒ⁶及びＲ⁷は、各々独立して、同一又は異なって、式：−Ｅ−Ａを表し、式中、Ｅは、単結合、又は以下の式1）〜14）：
1） −Ｃ（Ｒ¹⁶）Ｒ¹⁷−，
2） −Ｏ−，
3） −Ｓ（＝Ｏ）ｍ−，
4） −Ｓ（＝Ｏ）₂ＮＲ¹⁶−，
5） −Ｃ（＝Ｏ）−，
6） −Ｃ（＝Ｏ）Ｏ−，
7） −Ｃ（＝Ｏ）ＮＲ¹⁶−，
8） −Ｃ（＝ＮＲ¹⁶）ＮＲ¹⁷−，
9） −ＮＲ¹⁶−，
10） −Ｎ（Ｒ¹⁶）Ｃ（＝Ｏ）−，
11） −Ｎ（Ｒ¹⁶）Ｓ（＝Ｏ）₂−，
12） −Ｎ（Ｒ¹⁶）Ｃ（＝Ｏ）Ｎ（Ｒ¹⁷）−，
13） −Ｎ（Ｒ¹⁶）Ｓ（＝Ｏ）₂Ｎ（Ｒ¹⁷）−，
14） −Ｐ（＝Ｏ）（ＯＲ¹⁶）₂−
（式中、Ｒ¹⁶及びＲ¹⁷は、各々独立して、水素原子、炭素原子数が１〜３のアルキル基、又は炭素原子数が１〜３のアルコキシ基を表すか、又は式8）、12）及び13）においては、Ｒ¹⁶とＲ¹⁷は結合して、炭素原子数２〜４のアルキレン基を表してもよく、ｍは、０、１又は２を表す。）から選択される基を表し、
Ｅが単結合である時、Ａは、水素原子、ハロゲン原子、シアノ基、ニトロ基、水酸基、カルボキシル基、置換もしくは無置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、又は置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基を表し、
Ｅが前記式1）〜14）から選択される基を表す時、Ａは、水素原子、置換もしくは無置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、又は置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基を表す。〕
から選択される基を表し、
Ｒ⁸は、水素原子、炭素原子数が１〜３のアルキル基、又は１つ以上のハロゲン原子で置換された炭素原子数が１〜３のアルキル基を表し、
Ｒ⁹は、１つ以上のハロゲン原子で置換されたアルキル基、又は１つ以上のハロゲン原子で置換されたシクロアルキル基を表し、
Ｒ¹⁰は、水素原子、置換もしくは無置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、置換もしくは無置換のアルカノイル基、置換もしくは無置換のアルコキシカルボニル基、置換もしくは無置換のアルキルスルフィニル基、置換もしくは無置換のアルキルスルホニル基、置換もしくは無置換のアルケニルカルボニル基、置換もしくは無置換のアルケニルオキシカルボニル基、置換もしくは無置換のアルケニルスルフィニル基、置換もしくは無置換のアルケニルスルホニル基、置換もしくは無置換のシクロアルキルカルボニル基、置換もしくは無置換のシクロアルキルオキシカルボニル基、置換もしくは無置換のシクロアルキルスルフィニル基、置換もしくは無置換のシクロアルキルスルホニル基、置換もしくは無置換のアロイル基、置換もしくは無置換のアリールオキシカルボニル基、置換もしくは無置換のアリールスルフィニル基、置換もしくは無置換のアリールスルホニル基、置換もしくは無置換のヘテロアリールカルボニル基、置換もしくは無置換のヘテロアリールオキシカルボニル基、置換もしくは無置換のヘテロアリールスルフィニル基、置換もしくは無置換のヘテロアリールスルホニル基、置換もしくは無置換のアラルキルカルボニル基、置換もしくは無置換のアラルキルオキシカルボニル基、置換もしくは無置換のアラルキルスルフィニル基、置換もしくは無置換のアラルキルスルホニル基、置換もしくは無置換のヘテロアラルキルカルボニル基、置換もしくは無置換のヘテロアラルキルオキシカルボニル基、置換もしくは無置換のヘテロアラルキルスルフィニル基、置換もしくは無置換のヘテロアラルキルスルホニル基、置換もしくは無置換のカルバモイル基、置換もしくは無置換のスルファモイル基、置換もしくは無置換のチオカルバモイル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環カルボニル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環スルフィニル基、又は置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環スルホニル基を表す。］
で表される化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔２〕 Ｒ⁸が、水素原子を表し、Ｒ¹⁰が、水素原子、置換もしくは無置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、置換もしくは無置換のアルカノイル基、置換もしくは無置換のアルコキシカルボニル基、置換もしくは無置換のアルキルスルホニル基、置換もしくは無置換のアルケニルカルボニル基、置換もしくは無置換のアルケニルオキシカルボニル基、置換もしくは無置換のアルケニルスルホニル基、置換もしくは無置換のシクロアルキルカルボニル基、置換もしくは無置換のシクロアルキルオキシカルボニル基、置換もしくは無置換のシクロアルキルスルホニル基、置換もしくは無置換のアロイル基、置換もしくは無置換のアリールオキシカルボニル基、置換もしくは無置換のアリールスルホニル基、置換もしくは無置換のヘテロアリールカルボニル基、置換もしくは無置換のヘテロアリールオキシカルボニル基、置換もしくは無置換のヘテロアリールスルホニル基、置換もしくは無置換のアラルキルカルボニル基、置換もしくは無置換のアラルキルオキシカルボニル基、置換もしくは無置換のアラルキルスルホニル基、置換もしくは無置換のヘテロアラルキルカルボニル基、置換もしくは無置換のヘテロアラルキルオキシカルボニル基、置換もしくは無置換のヘテロアラルキルスルホニル基、置換もしくは無置換のカルバモイル基、置換もしくは無置換のスルファモイル基、置換もしくは無置換のチオカルバモイル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環カルボニル基、又は置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環スルホニル基を表すか、
またはＲ⁸が、炭素原子数が１〜３のアルキル基、又は１つ以上のハロゲン原子で置換された炭素原子数が１〜３のアルキル基を表し、Ｒ¹⁰が、置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、置換もしくは無置換のアルカノイル基、置換もしくは無置換のアルコキシカルボニル基、置換もしくは無置換のアルキルスルホニル基、置換もしくは無置換のアルケニルカルボニル基、置換もしくは無置換のアルケニルオキシカルボニル基、置換もしくは無置換のアルケニルスルホニル基、置換もしくは無置換のシクロアルキルカルボニル基、置換もしくは無置換のシクロアルキルオキシカルボニル基、置換もしくは無置換のシクロアルキルスルホニル基、置換もしくは無置換のアロイル基、置換もしくは無置換のアリールオキシカルボニル基、置換もしくは無置換のアリールスルホニル基、置換もしくは無置換のヘテロアリールカルボニル基、置換もしくは無置換のヘテロアリールオキシカルボニル基、置換もしくは無置換のヘテロアリールスルホニル基、置換もしくは無置換のアラルキルカルボニル基、置換もしくは無置換のアラルキルオキシカルボニル基、置換もしくは無置換のアラルキルスルホニル基、置換もしくは無置換のヘテロアラルキルカルボニル基、置換もしくは無置換のヘテロアラルキルオキシカルボニル基、置換もしくは無置換のヘテロアラルキルスルホニル基、置換もしくは無置換のカルバモイル基、置換もしくは無置換のスルファモイル基、置換もしくは無置換のチオカルバモイル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環カルボニル基、又は置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環スルホニル基を表し、当該置換のアルキル基の置換基が、置換もしくは無置換のアミノ基、置換もしくは無置換のアリールオキシ基、置換もしくは無置換のヘテロアリールオキシ基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環オキシ基、置換もしくは無置換のアリールチオ基、置換もしくは無置換のヘテロアリールチオ基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環チオ基、置換もしくは無置換のアリールスルホニル基、置換もしくは無置換のヘテロアリールスルホニル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環スルホニル基、置換もしくは無置換のアラルキルオキシ基、置換もしくは無置換のヘテロアラルキルオキシ基、置換もしくは無置換のアラルキルスルホニル基、置換もしくは無置換のヘテロアラルキルスルホニル基、置換もしくは無置換のカルバモイル基、置換もしくは無置換のスルファモイル基、置換もしくは無置換のチオカルバモイル基、又は置換もしくは無置換の飽和もしくは不飽和の脂肪族へテロ環基である、〔１〕に記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔３〕 −Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−が、式（ａ）：−ＣＲ⁴＝ＣＲ⁵−ＣＲ⁶＝ＣＲ⁷−（式中、Ｒ⁴、Ｒ⁵、Ｒ⁶及びＲ⁷は請求項１と同義である）を表す、〔１〕又は〔２〕に記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔４〕 −Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−が、式（ｄ）：−ＣＲ⁴＝ＣＲ⁵−Ｎ＝ＣＲ⁷−（式中、Ｒ⁴、Ｒ⁵及びＲ⁷は請求項１と同義である）を表す、〔１〕又は〔２〕に記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔５〕 Ｒ¹が、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルキル基で置換されたアルキル基、又は置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環で置換されたアルキル基を表す、〔１〕〜〔４〕のいずれかに記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔６〕 Ｒ²が、水素原子又は置換もしくは無置換の炭素数１〜６のアルキル基を表す、〔１〕〜〔５〕のいずれかに記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔７〕 Ｒ⁸が、水素原子を表す、〔１〕〜〔６〕のいずれかに記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔８〕 Ｒ⁹が、１〜７個のフッ素原子又は塩素原子で置換された炭素原子数が１〜６のアルキル基を表す、〔１〕〜〔７〕のいずれかに記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔９〕 Ｒ⁹が、トリフルオロメチル基を表す、〔８〕に記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔１０〕 Ｒ¹⁰が、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基で置換されたアルキル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基、置換もしくは無置換のアラルキルスルホニル基、置換もしくは無置換のヘテロアラルキルスルホニル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基で置換されたアルキルスルホニル基、置換もしくは無置換のアリールスルホニル基、置換もしくは無置換のヘテロアリールスルホニル基、または置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環スルホニル基を表す、〔１〕〜〔９〕のいずれかに記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩；
〔１１〕 〔１〕〜〔１０〕のいずれかに記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩を、有効成分として含有するグルココルチコイド受容体機能調節剤；
〔１２〕 〔１〕〜〔１０〕のいずれかに記載の化合物もしくはそのプロドラッグ、又はそれらの薬学上許容される塩を有効成分として含有する、炎症性疾患もしくは糖尿病の治療薬又は予防薬；
に関する。

[Wherein, R ¹ represents a substituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, substituted or unsubstituted Substituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted alkanoyl group, substituted or unsubstituted Substituted alkoxycarbonyl group, substituted or unsubstituted alkylsulfonyl group, substituted or unsubstituted cycloalkyloxy group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted cycloalkyloxycarbonyl group, substituted or unsubstituted Cycloalkylsulfo Group, substituted or unsubstituted aryloxy group, substituted or unsubstituted aroyl group, substituted or unsubstituted aryloxycarbonyl group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroaryloxy group, substituted Or an unsubstituted heteroarylcarbonyl group, a substituted or unsubstituted heteroaryloxycarbonyl group, a substituted or unsubstituted heteroarylsulfonyl group, a substituted or unsubstituted aralkyloxy group, a substituted or unsubstituted aralkylcarbonyl group, substituted or Unsubstituted aralkyloxycarbonyl group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkyloxy group, substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted heteroarral Killoxycarbonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic carbonyl group, substituted or Represents an unsubstituted saturated or unsaturated aliphatic heterocyclic sulfonyl group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted sulfamoyl group;
R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, substituted or unsubstituted Substituted aralkyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted alkanoyl group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted saturated or unsaturated An aliphatic heterocyclic group, or a carbamoyl group that may be substituted with a substituted or unsubstituted alkyl group,
^{-W 4 = W 5 -W 6 =} W 7 - has the following formula (a) ~ (h):
^{(A) -CR 4 = CR 5} -CR 6 = CR 7 -;
^{(B) -N = CR 5 -CR} 6 = CR 7 -;
^{(C) -CR 4 = N-} CR 6 = CR 7 -;
^{(D) -CR 4 = CR 5} -N = CR 7 -;
^{(E) -CR 4 = CR 5} -CR 6 = N-;
^{(F) -N = CR 5 -N} = CR 7 -;
^{(G) -CR 4 = N-} CR 6 = N-;
^{(H) -CR 4 = N-} N = CR 7 -
[Wherein, R ⁴ , R ⁵ , R ⁶ and R ⁷ are each independently the same or different and represent the formula: -EA, wherein E is a single bond or the following formula 1 )~14):
1) -C (R ¹⁶ ) R ^17- ,
2) -O-,
3) -S (= O) m-,
4) -S (= O) ₂ NR ^16- ,
5) -C (= O)-,
6) -C (= O) O-,
7) -C (= O) NR ^16- ,
8) −C (= NR ¹⁶ ) NR ¹⁷ −,
9) -NR ^16- ,
^{10) -N (R 16) C} (= O) -,
11) -N (R ¹⁶ ) S (= O) _2- ,
^{12) -N (R 16) C} (= O) N (R 17) -,
^{13) -N (R 16) S} (= O) 2 N (R 17) -,
14) -P (= O) (OR ¹⁶ ) _2-
(Wherein R ¹⁶ and R ¹⁷ each independently represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an alkoxy group having 1 to 3 carbon atoms, or formula 8). In 12) and 13), R ¹⁶ and R ¹⁷ may be bonded to each other to represent an alkylene group having 2 to 4 carbon atoms, and m represents 0, 1 or 2. ) Represents a group selected from
When E is a single bond, A is a hydrogen atom, halogen atom, cyano group, nitro group, hydroxyl group, carboxyl group, substituted or unsubstituted alkyl group, substituted or unsubstituted alkenyl group, substituted or unsubstituted alkynyl. Group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted cycloalkenyl group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted Represents a heteroaralkyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group,
When E represents a group selected from the above formulas 1) to 14), A represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, substituted or An unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, Or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group. ]
Represents a group selected from
R ⁸ represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an alkyl group having 1 to 3 carbon atoms substituted with one or more halogen atoms,
R ⁹ represents an alkyl group substituted with one or more halogen atoms, or a cycloalkyl group substituted with one or more halogen atoms;
R ¹⁰ represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, substituted Or an unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, a substituted or unsubstituted alkanoyl group, a substituted or unsubstituted alkoxycarbonyl group, Substituted or unsubstituted alkylsulfinyl group, substituted or unsubstituted alkylsulfonyl group, substituted or unsubstituted alkenylcarbonyl group, substituted or unsubstituted alkenyloxycarbonyl group, substituted or unsubstituted alkenylsulfinyl group, substituted or unsubstituted of Lucenylsulfonyl group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted cycloalkyloxycarbonyl group, substituted or unsubstituted cycloalkylsulfinyl group, substituted or unsubstituted cycloalkylsulfonyl group, substituted or unsubstituted Aroyl group, substituted or unsubstituted aryloxycarbonyl group, substituted or unsubstituted arylsulfinyl group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylcarbonyl group, substituted or unsubstituted heteroaryloxy Carbonyl group, substituted or unsubstituted heteroarylsulfinyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted aralkylcarbonyl group, substituted or unsubstituted aralkylo Sicarbonyl group, substituted or unsubstituted aralkylsulfinyl group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted heteroaralkyloxycarbonyl group, substituted or unsubstituted heteroaralkyl Sulfinyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, substituted or unsubstituted thiocarbamoyl group, substituted or unsubstituted saturated or unsaturated aliphatic Heterocyclic group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic carbonyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic sulfinyl group, or substituted or unsubstituted saturated or unsaturated Represents an aliphatic heterocyclic sulfonyl group. ]
Or a prodrug thereof, or a pharmaceutically acceptable salt thereof;
[2] R ⁸ represents a hydrogen atom, and R ¹⁰ represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl Group, substituted or unsubstituted cycloalkenyl group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted Alkanoyl group, substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted alkylsulfonyl group, substituted or unsubstituted alkenylcarbonyl group, substituted or unsubstituted alkenyloxycarbonyl group, substituted or unsubstituted alkenylsulfonyl group, substituted Or unsubstituted cycloalkyl alkyl Bonyl group, substituted or unsubstituted cycloalkyloxycarbonyl group, substituted or unsubstituted cycloalkylsulfonyl group, substituted or unsubstituted aroyl group, substituted or unsubstituted aryloxycarbonyl group, substituted or unsubstituted arylsulfonyl group Substituted or unsubstituted heteroarylcarbonyl group, substituted or unsubstituted heteroaryloxycarbonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted aralkylcarbonyl group, substituted or unsubstituted aralkyloxycarbonyl group Substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted heteroaralkyloxycarbonyl group, substituted or unsubstituted heteroaralkyl Sulfonyl group, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, substituted or unsubstituted thiocarbamoyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted saturated Or an unsaturated aliphatic heterocyclic carbonyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic sulfonyl group,
Or R ⁸ represents an alkyl group having 1 to 3 carbon atoms, or an alkyl group having 1 to 3 carbon atoms substituted with one or more halogen atoms, and R ¹⁰ represents a substituted alkyl group or substituted Or an unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, Substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted alkanoyl group, substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted alkylsulfonyl group, substituted or unsubstituted alkenylcarbonyl Group, substituted or unsubstituted alkenyloxycarbonyl group, substituted or Substituted alkenylsulfonyl group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted cycloalkyloxycarbonyl group, substituted or unsubstituted cycloalkylsulfonyl group, substituted or unsubstituted aroyl group, substituted or unsubstituted Aryloxycarbonyl group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylcarbonyl group, substituted or unsubstituted heteroaryloxycarbonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted Aralkylcarbonyl group, substituted or unsubstituted aralkyloxycarbonyl group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted hetero Aralkyloxycarbonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, substituted or unsubstituted thiocarbamoyl group, substituted or unsubstituted saturated or unsaturated Represents an aliphatic heterocyclic group, a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic carbonyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic sulfonyl group, and the substitution of the substituted alkyl group The group is substituted or unsubstituted amino group, substituted or unsubstituted aryloxy group, substituted or unsubstituted heteroaryloxy group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic oxy group, substituted or unsubstituted Substituted arylthio groups, substituted or unsubstituted hete Arylthio group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic thio group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted saturated or unsaturated fat Heterocyclic sulfonyl group, substituted or unsubstituted aralkyloxy group, substituted or unsubstituted heteroaralkyloxy group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted carbamoyl The compound or prodrug thereof according to [1], which is a group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group Or their pharmacological permit Salts;
[3] ^{-W 4 = W 5 -W 6 =} W 7 - is of the formula ^{(a): - CR 4 =} CR 5 -CR 6 = CR 7 - ( wherein, R ^4, R ^5, R ⁶ and R ⁷ is as defined in claim 1, and the compound according to [1] or [2] or a prodrug thereof, or a pharmaceutically acceptable salt thereof;
[4] ^{-W 4 = W 5 -W 6 =} W 7 - is of formula ^{(d): - CR 4 =} CR 5 -N = CR 7 - ( wherein, R ^4, R ⁵ and R ⁷ claims Or a prodrug thereof, or a pharmaceutically acceptable salt thereof, which represents the same as 1);
[5] R ¹ represents a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted cycloalkyl group, Any one of [1] to [4], which represents an alkyl group substituted with a substituted or unsubstituted cycloalkyl group, or an alkyl group substituted with a substituted or unsubstituted saturated or unsaturated aliphatic heterocycle The described compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof;
[6] The compound according to any one of [1] to [5], wherein R ² represents a hydrogen atom or a substituted or unsubstituted alkyl group having 1 to 6 carbon atoms, or a prodrug thereof, or a pharmaceutical thereof Acceptable salts;
[7] The compound according to any one of [1] to [6], wherein R ⁸ represents a hydrogen atom, or a prodrug thereof, or a pharmaceutically acceptable salt thereof;
[8] The compound according to any one of [1] to [7] or a compound thereof, wherein R ⁹ represents an alkyl group having 1 to 6 carbon atoms substituted with 1 to 7 fluorine atoms or chlorine atoms. Prodrugs, or pharmaceutically acceptable salts thereof;
[9] The compound according to [8], wherein R ⁹ represents a trifluoromethyl group, or a prodrug thereof, or a pharmaceutically acceptable salt thereof;
[10] R ¹⁰ is a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, an alkyl group substituted with a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted Aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or An alkylsulfonyl group substituted with an unsubstituted saturated or unsaturated aliphatic heterocyclic group, a substituted or unsubstituted arylsulfonyl group, a substituted or unsubstituted heteroarylsulfonyl group, or a substituted or unsubstituted saturated or unsaturated group [1] to [9], which represents an aliphatic heterocyclic sulfonyl group of Or a prodrug thereof, or a pharmaceutically acceptable salt thereof;
[11] A glucocorticoid receptor function modulator comprising the compound according to any one of [1] to [10] or a prodrug thereof, or a pharmaceutically acceptable salt thereof as an active ingredient;
[12] A therapeutic or prophylactic agent for inflammatory diseases or diabetes comprising the compound according to any one of [1] to [10] or a prodrug thereof, or a pharmaceutically acceptable salt thereof as an active ingredient;
About.

According to the present invention, a compound having a novel condensed pyrrole skeleton, a prodrug thereof, or a pharmaceutically acceptable compound thereof useful as a glucocorticoid function modulator (modulator), that is, a therapeutic or prophylactic agent for inflammatory diseases or diabetes. It has become possible to provide the salt to be made.

Hereinafter, the present invention will be described more specifically.
The description of each group in the present invention also applies to the case where the group is a part of another group, unless otherwise specified.
The number of substituents in the present specification is not particularly limited as long as substitution is possible, and is 1 or more, preferably 1 to 5.

  In the present specification, examples of the “halogen atom” include a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

  Examples of the “alkyl group” include linear or branched alkyl groups having 1 to 10 carbon atoms, specifically, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group. , Sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group, 1-methylbutyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, etc. it can. Among them, preferred is an alkyl group having 1 to 6 carbon atoms.

  Examples of the “alkenyl group” include linear or branched alkenyl groups having 2 to 6 carbon atoms, specifically, vinyl group, 1-propenyl group, allyl group (2-propenyl group), Isopropenyl group (1-methylvinyl group), 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-1-propenyl group, 1-methyl-2-propenyl group, 2-methylallyl group, 1 -An ethyl vinyl group, 1-pentenyl group, 1-hexenyl group, etc. can be mentioned. Among them, preferred is an alkenyl group having 2 to 4 carbon atoms.

Examples of the “alkynyl group” include linear or branched alkynyl groups having 2 to 6 carbon atoms, and specifically include an ethynyl group, a 1-propynyl group, a 2-propynyl group, and a 1-butynyl group. 1-methyl-2-propynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, or 1-hexynyl group. Among them, preferred is an alkynyl group having 2 to 4 carbon atoms.

  Examples of the “cycloalkyl group” include 3- to 10-membered saturated monocyclic to tricyclic aliphatic hydrocarbon ring groups, and specifically include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group. A cycloheptyl group, a cyclooctyl group, a bicyclo [3,2,1] octyl group, a bicyclo [2,2,2] octyl group, or an adamantyl group. Of these, a 4- to 6-membered saturated cycloalkyl group is preferable.

  Examples of the “cycloalkenyl group” include a 4- to 10-membered monocyclic to tricyclic aliphatic hydrocarbon group containing 1 or 2 double bonds in the ring, specifically, a cyclobutenyl group. , Cyclopentenyl group, cyclohexenyl group, cycloheptenyl group, or cyclooctenyl group, and the bonding position is not particularly limited. Among them, a 4- to 6-membered cycloalkenyl group is preferable.

  Examples of the “aryl group” include an aryl group having 6 to 10 carbon atoms, and specific examples include a phenyl group, a 1-naphthyl group, and a 2-naphthyl group.

  The “heteroaryl group” is a monocyclic 5-membered member containing 1 to 4 heteroatoms selected from 0 to 4 nitrogen atoms, 0 to 2 oxygen atoms and 0 to 2 sulfur atoms. Alternatively, a 6-membered heteroaryl group or a bicyclic 9-membered or 10-membered heteroaryl group can be mentioned, and the bonding position is not particularly limited as long as it is chemically stable. Specifically, furyl group, thienyl group, pyrrolyl group, oxazolyl group, isoxazolyl group, thiazolyl group, isothiazolyl group, imidazolyl group, pyrazolyl group, oxadiazolyl group, thiadiazolyl group, triazolyl group, pyridyl group, pyridazinyl group, pyrimidinyl group, Pyrazinyl group, tetrazolyl group, indolyl group, benzofuranyl group, benzothiophenyl group, benzoxazolyl group, benzisoxazolyl group, benzothiazolyl group, benzimidazolyl group, quinolyl group, isoquinolyl group, quinazolinyl group, imidazopyridinyl group Or a prynyl group.

  The “aralkyl group” is also referred to as an arylalkyl group, and examples of the “aralkyl group” include a linear or branched alkyl group having 1 to 6 carbon atoms substituted with an aryl group. Examples of the aryl group and the alkyl group are the same as described above. Specific examples of the aralkyl group include benzyl group (phenylmethyl group), phenethyl group (2-phenylethyl group), 3-phenylpropyl group, 2-phenyl-2-methylethyl group, 1-phenylethyl group, 1 -Naphthylmethyl, 2-naphthylmethyl, etc. can be mentioned.

  The “heteroaralkyl group” is also called a heteroarylalkyl group, and examples of the “heteroaralkyl group” include a linear or branched alkyl group having 1 to 6 carbon atoms substituted with a heteroaryl group. It is done. Examples of the heteroaryl group and the alkyl group include those described above, and the bonding position between the heteroaryl group and the alkyl group is not particularly limited as long as it is chemically stable. Specific examples of the heteroaralkyl group include a furylmethyl group, a furylethyl group, a thienylmethyl group, a thienylethyl group, a pyrrolylmethyl group, a pyrrolylethyl group, an oxazolylmethyl group, an oxazolylethyl group, an isoxazolylmethyl group, Isoxazolylethyl, thiazolylmethyl, thiazolylethyl, isothiazolylmethyl, isothiazolylethyl, imidazolylmethyl, imidazolylethyl, pyrazolylmethyl, pyrazolylethyl, oxadiazolylmethyl, oxadiazolyl Ethyl group, thiadiazolylmethyl group, thiadiazolylethyl group, pyridylmethyl group, pyridylethyl group, pyridazinylmethyl group, pyridazinylethyl group, pyrimidinylmethyl group, pyrimidinylethyl group, pyrazinylmethyl group, pyrazinylethyl group Group, triazolylmethyl group, triazolylethyl group, tetrazolylmethyl group, tetrazolylethyl group, benzofuranylmethyl group, benzofuranylethyl group, benzothiophenylmethyl group, or benzothiophenylethyl group Etc.

  Examples of the “alkoxy group” include linear or branched alkoxy groups having 1 to 10 carbon atoms, and specifically include methoxy group, ethoxy group, propoxy group, isopropoxy group, butoxy group, isobutoxy group. Group, sec-butoxy group, tert-butoxy group, pentyloxy group, isopentyloxy group, neopentyloxy group, tert-pentyloxy group, 1-methylbutoxy group, hexyloxy group, heptyloxy group, octyloxy group, Nonyloxy group, decyloxy group, etc. can be mentioned. Among them, preferred is an alkoxy group having 1 to 6 carbon atoms.

  The “alkanoyl group”, which is also called an acyl group, includes a linear or branched alkanoyl group having 2 to 10 carbon atoms, and specifically includes an acetyl group, a propionyl group, a butyryl group, and an isobutyryl group. , Valeryl group, isovaleryl group, pivaloyl group, hexanoyl group, heptanoyl group, octanoyl group, nonanoyl group, decanoyl group, and the like. Among them, preferred is an alkanoyl group having 2 to 6 carbon atoms.

  The “alkanoyl” in the “alkanoyloxy group” has the same meaning as the “alkanoyl group”.

  Examples of the “alkoxycarbonyl group” include linear or branched alkoxycarbonyl groups having 2 to 11 carbon atoms, and specifically include methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group. Group, butoxycarbonyl group, isobutoxycarbonyl group, sec-butoxycarbonyl group, tert-butoxycarbonyl group, pentyloxycarbonyl group, isopentyloxycarbonyl group, neopentyloxycarbonyl group, tert-pentyloxycarbonyl group, 1-methyl Examples thereof include a butoxycarbonyl group, a hexyloxycarbonyl group, a heptyloxycarbonyl group, an octyloxycarbonyl group, a nonyloxycarbonyl group, and a decyloxycarbonyl group. Among them, preferred is an alkoxycarbonyl group having 2 to 7 carbon atoms.

  Examples of the “alkylthio group” include linear or branched alkylthio groups having 1 to 10 carbon atoms, and specifically include methylthio group, ethylthio group, propylthio group, isopropylthio group, butylthio group, isobutyl group. Thio group, sec-butylthio group, tert-butylthio group, pentylthio group, isopentylthio group, neopentylthio group, tert-pentylthio group, 1-methylbutylthio group, hexylthio group, heptylthio group, octylthio group, nonylthio group, Or a decylthio group can be mentioned. Among them, preferred is an alkylthio group having 1 to 6 carbon atoms.

  Examples of the “alkylsulfinyl group” include linear or branched alkylsulfinyl groups having 1 to 10 carbon atoms, specifically, methylsulfinyl group, ethylsulfinyl group, propylsulfinyl group, isopropylsulfinyl group. Butylsulfinyl group, isobutylsulfinyl group, sec-butylsulfinyl group, tert-butylsulfinyl group, pentylsulfinyl group, isopentylsulfinyl group, neopentylsulfinyl group, tert-pentylsulfinyl group, 1-methylbutylsulfinyl group, hexylsulfinyl group A group, heptylsulfinyl group, octylsulfinyl group, nonylsulfinyl group, or decylsulfinyl group. Among them, preferred is an alkylsulfinyl group having 1 to 6 carbon atoms.

  Examples of the “alkylsulfonyl group” include linear or branched alkylsulfonyl groups having 1 to 10 carbon atoms, specifically, methylsulfonyl group, ethylsulfonyl group, propylsulfonyl group, isopropylsulfonyl group. Butylsulfonyl group, isobutylsulfonyl group, sec-butylsulfonyl group, tert-butylsulfonyl group, pentylsulfonyl group, isopentylsulfonyl group, neopentylsulfonyl group, tert-pentylsulfonyl group, 1-methylbutylsulfonyl group, hexylsulfonyl A group, a heptylsulfonyl group, an octylsulfonyl group, a nonylsulfonyl group, or a decylsulfonyl group. Among them, preferred is an alkylsulfonyl group having 1 to 6 carbon atoms.

  “Alkylene” includes linear or branched alkylene having 1 to 10 carbon atoms, specifically, methylene, ethylene, trimethylene, 1-methylmethylene, 1-methylethylene, tetramethylene, Examples include octamethylene and decamethylene. Among them, preferred is alkylene having 1 to 6 carbon atoms.

  The “saturated aliphatic heterocyclic group” includes 1 to 4 heteroatoms selected from 0 to 4 nitrogen atoms, 0 to 2 oxygen atoms and 0 to 2 sulfur atoms. A 10-membered monocyclic or bicyclic saturated aliphatic heterocyclic group is exemplified, and the bonding position is not particularly limited as long as it is chemically stable. Specifically, azetidinyl group, pyrrolidinyl group, piperidyl group, piperidino group, piperazinyl group, azepanyl group, azocanyl group, tetrahydrofuryl group, tetrahydrothienyl group, tetrahydropyranyl group, morpholinyl group, morpholino group, thiomorpholinyl group, 1- Oxothiomorpholinyl group, 1,1-dioxothiomorpholinyl group, thiomorpholino group, 1-oxothiomorpholino group, 1,1-dioxothiomorpholino group, 1,3-dioxolanyl group, 1,4 -A dioxanyl group, a decahydroquinolino group, a decahydroquinoxalino, a 1,4-diazabicyclo [4.4.0] decano group, or a decahydroisoquinolino can be mentioned.

  The “unsaturated aliphatic heterocyclic group” includes 1 to 4 heteroatoms selected from 0 to 4 nitrogen atoms, 0 to 2 oxygen atoms and 0 to 2 sulfur atoms, Examples thereof include a 5- to 10-membered monocyclic or bicyclic unsaturated aliphatic heterocyclic group having no aromatic attribute and containing one or two double bonds, and the bonding position is not particularly limited as long as it is chemically stable. Specific examples include a 2-pyrrolinyl group, a 3-pyrrolinyl group, a 2-imidazolinyl group, a 3-imidazolinyl group, a 2-pyrazolinyl group, a 3-pyrazolinyl group, and an octahydroquinolinyl group.

  “Saturated or unsaturated aliphatic heterocyclic oxy group” means a group in which an oxygen atom is bonded to any carbon atom of the above “saturated aliphatic heterocyclic group” or “unsaturated aliphatic heterocyclic group”. Represents.

  “Saturated or unsaturated aliphatic heterocyclic carbonyl group” means a group in which a carbonyl group is bonded to any carbon atom of the above “saturated aliphatic heterocyclic group” or “unsaturated aliphatic heterocyclic group”. Represents.

“Saturated or unsaturated aliphatic heterocyclic sulfonyl group” means that sulfonyl (SO ₂ ) is present at any carbon atom of the above “saturated aliphatic heterocyclic group” or “unsaturated aliphatic heterocyclic group”. Represents a bonded group.

  “Saturated or unsaturated aliphatic heterocyclic sulfinyl group” means that sulfinyl (SO) is bonded to any carbon atom of the above “saturated aliphatic heterocyclic group” or “unsaturated aliphatic heterocyclic group”. Represents the group.

  “Saturated or unsaturated aliphatic heterocyclic thio group” means that thio (S) is bonded to any carbon atom of the above “saturated aliphatic heterocyclic group” or “unsaturated aliphatic heterocyclic group”. Represents the group.

  “Saturated or unsaturated aliphatic heterocyclic oxycarbonyl group” means a carbonyl on the oxygen atom outside the ring of the above “saturated aliphatic heterocyclic oxy group” or “unsaturated aliphatic heterocyclic oxy group”. A group to which a group is bonded is represented.

  The “aroyl group” is also referred to as an arylcarbonyl group. Examples of the “aroyl group” include a carbonyl group having an aryl group having 6 to 10 carbon atoms, specifically, a benzoyl group and a 1-naphthoyl group. Or a 2-naphthoyl group.

  The cycloalkyl part in the “cycloalkyloxy group”, “cycloalkylcarbonyl group”, “cycloalkyloxycarbonyl group”, “cycloalkylthio group”, “cycloalkylsulfinyl group”, and “cycloalkylsulfonyl group” is as defined above. It is.

  The cycloalkenyl moiety in the “cycloalkenyloxy group”, “cycloalkenylcarbonyl group”, “cycloalkenyloxycarbonyl group”, “cycloalkenylthio group”, “cycloalkenylsulfinyl group”, and “cycloalkenylsulfonyl group” is as defined above. It is synonymous.

  The aryl moiety in the “aryloxy group”, “aryloxycarbonyl group”, “arylthio group”, “arylsulfinyl group”, and “arylsulfonyl group” has the same meaning as described above.

  The heteroaryl moiety in the “heteroaryloxy group”, “heteroarylcarbonyl group”, “heteroaryloxycarbonyl group”, “heteroarylthio group”, “heteroarylsulfinyl group”, and “heteroarylsulfonyl group” is as defined above. It is the same.

  The aralkyl moiety in the “aralkyloxy group”, “aralkylcarbonyl group”, “aralkyloxycarbonyl group”, “aralkylthio group”, “aralkylsulfinyl group”, and “aralkylsulfonyl group” is as defined above.

The heteroaralkyl moiety in the “heteroaralkyloxy group”, “heteroaralkylcarbonyl group”, “heteroaralkyloxycarbonyl group”, “heteroaralkylthio group”, “heteroaralkylsulfinyl group”, and “heteroaralkylsulfonyl group” It is synonymous.

“Alkyl group”, “alkenyl group”, “alkynyl group”, “alkoxy group”, “alkanoyl group”, “alkoxycarbonyl group”, “alkylthio group”, “alkylsulfinyl group” or “alkylsulfonyl group” substituted In this case, the substituent is selected from the following groups (i) to (v), and 1 to 6 identical or different substituents may be substituted:
(I) halogen atom, hydroxyl group, carboxyl group, cyano group, formyl group, oxo group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH) ₂ );
(Ii) a substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group;
(Iii) alkoxy group, alkanoyl group, alkanoyloxy group, alkoxycarbonyl group, alkylthio group, alkylsulfinyl group, alkylsulfonyl group;
[These groups are selected from a halogen atom, a hydroxyl group, a carboxyl group, a substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, and a substituted or unsubstituted thiocarbamoyl group. It may be substituted with a substituent. ];
(Iv) a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkyloxy group, a substituted or unsubstituted cycloalkylcarbonyl group, a substituted or unsubstituted cycloalkyloxycarbonyl group, a substituted or unsubstituted cycloalkylthio Group, substituted or unsubstituted cycloalkylsulfonyl group, substituted or unsubstituted cycloalkylsulfinyl group, substituted or unsubstituted cycloalkenyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted A substituted saturated or unsaturated aliphatic heterocyclic oxy group, a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic sulfonyl group, a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic carbonyl group, substituted or Unsubstituted saturated or unsaturated aliphatic heterocyclic thio , Substituted or unsubstituted, saturated or unsaturated aliphatic heterocyclic sulfinyl group, a substituted or unsubstituted, saturated or unsaturated aliphatic heterocyclic oxycarbonyl group;
(V) a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aroyl group, a substituted or unsubstituted heteroarylcarbonyl group, a substituted or unsubstituted aryloxy group, substituted or unsubstituted Substituted heteroaryloxy group, substituted or unsubstituted aryloxycarbonyl group, substituted or unsubstituted heteroaryloxycarbonyl group, substituted or unsubstituted arylthio group, substituted or unsubstituted heteroarylthio group, substituted or unsubstituted Arylsulfonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted arylsulfinyl group, substituted or unsubstituted heteroarylsulfinyl group, substituted or unsubstituted aralkyloxy group, substituted or unsubstituted arral Kill carbonyl group, substituted or unsubstituted aralkyloxycarbonyl group, substituted or unsubstituted aralkylthio group, substituted or unsubstituted aralkylsulfinyl group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkyloxy group , Substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted heteroaralkyloxycarbonyl group, substituted or unsubstituted heteroaralkylthio group, substituted or unsubstituted heteroaralkylsulfinyl group, substituted or unsubstituted heteroaralkylsulfonyl Group.

“Cycloalkyl group”, “cycloalkenyl group”, “cycloalkyloxy group”, “cycloalkylcarbonyl group”, “cycloalkyloxycarbonyl group”, “cycloalkylthio group”, “cycloalkylsulfinyl group”, “cycloalkyl” “Sulfonyl group”, “saturated or unsaturated aliphatic heterocyclic group”, “saturated or unsaturated aliphatic heterocyclic oxy group”, “saturated or unsaturated aliphatic heterocyclic carbonyl group”, “saturated or unsaturated” An aliphatic heterocyclic oxycarbonyl group ”,“ saturated or unsaturated aliphatic heterocyclic sulfonyl group ”,“ saturated or unsaturated aliphatic heterocyclic sulfinyl group ”, or“ saturated or unsaturated aliphatic heterocyclic thio ” When the “group” is substituted, the substituent is selected from the following groups (vi) to (ix) One or five different substituents may be substituted:
(Vi) halogen atom, hydroxyl group, carboxyl group, cyano group, nitro group, oxo group, thioxo group, formyl group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH) ₂ );
(Vii) A substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted hetero group An aryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted heteroaryloxy group, a substituted or unsubstituted aroyl group, a substituted or unsubstituted heteroarylcarbonyl group, a substituted or unsubstituted aryloxycarbonyl group, Substituted or unsubstituted heteroaryloxycarbonyl group, substituted or unsubstituted arylthio group, substituted or unsubstituted heteroarylthio group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or Nothing Substituted arylsulfinyl group, substituted or unsubstituted heteroarylsulfinyl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted aralkyloxy group, substituted or unsubstituted aralkylcarbonyl group, substituted or unsubstituted aralkyloxycarbonyl Group, substituted or unsubstituted aralkylthio group, aralkylsulfinyl group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted heteroaralkyloxy group, substituted or unsubstituted heteroaralkyl A carbonyl group, a substituted or unsubstituted heteroaralkyloxycarbonyl group, a substituted or unsubstituted heteroaralkylthio group, a substituted or unsubstituted heteroaralkylsulfinyl group, a substituted or unsubstituted B aralkyl sulfonyl group;
(Viii) an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkanoyl group, an alkanoyloxy group, an alkoxycarbonyl group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group [these groups are represented by the following (1) to (3 ):
(1) a halogen atom, a hydroxyl group, a carboxyl group, a formyl group, a sulfo group (—SO ₂ OH), a phosphono group (—PO (OH) ₂ ), a substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, A substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group;
(2) an alkoxy group, an alkanoyl group, an alkoxycarbonyl group, an alkanoyloxy group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group (groups of this group are halogen atoms, hydroxyl groups, carboxyl groups, alkoxy groups, substituted or unsubstituted groups) An amino group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted sulfamoyl group).
(3) Cycloalkyl group, cycloalkyloxy group, cycloalkylsulfonyl group, cycloalkylcarbonyl group, cycloalkyloxycarbonyl group, cycloalkylthio group, cycloalkylsulfinyl group, cycloalkenyl group, cycloalkenyloxy group, cycloalkenylsulfonyl group , Cycloalkenylthio group, cycloalkenylcarbonyl group, cycloalkenyloxycarbonyl group, cycloalkenylsulfinyl group, saturated or unsaturated aliphatic heterocyclic group, saturated or unsaturated aliphatic heterocyclic oxy group, saturated or unsaturated Aliphatic heterocyclic sulfonyl group, saturated or unsaturated aliphatic heterocyclic thio group, saturated or unsaturated aliphatic heterocyclic carbonyl group, saturated or unsaturated aliphatic heterocyclic oxycarbonyl group, saturated or unsaturated fat Heterocycle Finyl group, aryl group, aryloxy group, arylthio group, arylsulfonyl group, aroyl group, aryloxycarbonyl group, arylsulfinyl group, heteroaryl group, heteroaryloxy group, heteroarylthio group, heteroarylsulfonyl group, heteroaryl Carbonyl group, heteroaryloxycarbonyl group, heteroarylsulfinyl group (groups of this group are halogen atom, hydroxyl group, carboxyl group, formyl group, cyano group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH ) _2), a carboxyl group or an alkoxycarbonyl alkyl group which may be substituted with a group, a carboxyl group or alkoxycarbonyl alkenyl group which may be substituted with a group, an alkoxy group, an alkanoyl group, an alkoxycarbonyl group, also substituted Ku may be substituted by unsubstituted amino group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted sulfamoyl group)
May be substituted with the same or different 1 to 5 substituents selected from ];
(Ix) a cycloalkyl group, a cycloalkenyl group, a cycloalkoxy group, a cycloalkylcarbonyl group, a cycloalkoxycarbonyl group, a cycloalkylthio group, a cycloalkylsulfonyl group, a cycloalkylsulfinyl group, a saturated or unsaturated aliphatic heterocyclic group, Saturated or unsaturated aliphatic heterocyclic oxy group, saturated or unsaturated aliphatic heterocyclic carbonyl group, saturated or unsaturated aliphatic heterocyclic sulfonyl group, saturated or unsaturated aliphatic heterocyclic thio group, saturated or Unsaturated aliphatic heterocyclic oxycarbonyl group, saturated or unsaturated aliphatic heterocyclic sulfinyl group [These groups are the following (1) to (3):
(1) Halogen atom, hydroxyl group, carboxyl group, formyl group, cyano group, nitro group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH) ₂ ), substituted or unsubstituted amino group, substituted or An unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group;
(2) an alkyl group, an alkoxy group, an alkanoyl group, an alkoxycarbonyl group, an alkanoyloxy group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group (groups of this group are halogen atoms, hydroxyl groups, carboxyl groups, alkoxy groups, substituted or An optionally substituted amino group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted sulfamoyl group);
(3) Cycloalkyl group, cycloalkyloxy group, cycloalkylsulfonyl group, cycloalkylcarbonyl group, cycloalkyloxycarbonyl group, cycloalkylthio group, cycloalkylsulfinyl group, cycloalkenyl group, saturated or unsaturated aliphatic heterocycle Group, saturated or unsaturated aliphatic heterocyclic oxy group, saturated or unsaturated aliphatic heterocyclic sulfonyl group, saturated or unsaturated aliphatic heterocyclic thio group, saturated or unsaturated aliphatic heterocyclic carbonyl group, Saturated or unsaturated aliphatic heterocyclic oxycarbonyl group, saturated or unsaturated aliphatic heterocyclic sulfinyl group, aryl group, aryloxy group, arylthio group, arylsulfonyl group, aroyl group, aryloxycarbonyl group, arylsulfinyl group , Heteroaryl group, heteroaryl Xyl group, heteroarylthio group, heteroarylsulfonyl group, heteroarylcarbonyl group, heteroaryloxycarbonyl group, heteroarylsulfinyl group, aralkyl group, aralkyloxy group, aralkylcarbonyl group, aralkyloxycarbonyl group, aralkylthio group, aralkyl Sulfinyl group, aralkylsulfonyl group, heteroaralkyl group, heteroaralkyloxy group, heteroaralkylcarbonyl group, heteroaralkyloxycarbonyl group, heteroaralkylthio group, heteroaralkylsulfinyl group, heteroaralkylsulfonyl group (the group in this group is a halogen atom) , a hydroxyl group, a carboxyl group, a formyl group, a cyano group, a sulfo group (-SO ₂ OH), a phosphono group (-PO (OH) _2), a carboxyl group or alkoxycarbonyl Alkyl group which may be substituted with, alkenyl group which may be substituted with carboxyl group or alkoxycarbonyl group, alkoxy group, alkanoyl group, alkoxycarbonyl group, substituted or unsubstituted amino group, substituted or unsubstituted carbamoyl Group or a substituted or unsubstituted sulfamoyl group)
May be substituted with the same or different 1 to 5 substituents selected from ].

“Aryl group”, “aryloxy group”, “aroyl group”, “aryloxycarbonyl group”, “arylthio group”, “arylsulfinyl group”, “arylsulfonyl group”, “heteroaryl group”, “heteroaryloxy” Group, heteroarylcarbonyl group, heteroaryloxycarbonyl group, heteroarylthio group, heteroarylsulfinyl group, heteroarylsulfonyl group, aralkyl group, aralkyloxy group, "Aralkylcarbonyl group", "Aralkyloxycarbonyl group", "Aralkylthio group", "Aralkylsulfinyl group", "Aralkylsulfonyl group", "Heteroaralkyl group", "Heteroaralkyloxy group", "Heteroaralkylcarbonyl group" , "Hetero Aralkyl Oki The substituent when the “carbonyl group”, “heteroaralkylthio group”, “heteroaralkylsulfinyl group” or “heteroaralkylsulfonyl group” is substituted is selected from the following groups (x) to (xiv) 1 to 5 of the same or different substituents may be substituted:
(X) halogen atom, hydroxyl group, carboxyl group, cyano group, nitro group, formyl group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH) ₂ );
(Xi) a substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group;
(Xii) an alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkanoyl group, an alkanoyloxy group, an alkoxycarbonyl group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group [these groups are represented by the following (1) to (4 ):
(1) Halogen atom, hydroxyl group, carboxyl group, formyl group, oxo group, cyano group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH) ₂ );
(2) a substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group;
(3) alkoxy group, alkoxycarbonyl group, alkylthio group, alkylsulfinyl group, alkylsulfonyl group
[This group is based on the following (a) or (b):
(a) a halogen atom, a hydroxyl group, a carboxyl group, an alkoxy group, a substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group;
(b) Cycloalkyl group, cycloalkyloxy group, cycloalkylthio group, cycloalkylsulfinyl group, cycloalkylsulfonyl group, cycloalkenyl group, cycloalkenyloxy group, saturated or unsaturated aliphatic heterocyclic group, saturated or unsaturated Aliphatic heterocyclic oxy group, saturated or unsaturated aliphatic heterocyclic thio group, saturated or unsaturated aliphatic heterocyclic sulfinyl group, saturated or unsaturated aliphatic heterocyclic sulfonyl group, aryl group, aryloxy group An arylthio group, an arylsulfonyl group, an arylsulfinyl group, a heteroaryl group, a heteroaryloxy group, a heteroarylthio group, a heteroarylsulfonyl group, a heteroarylsulfinyl group (groups of this group include a halogen atom, a hydroxyl group, a carboxyl group, Formyl group, cyano group, sulfo (-SO ₂ OH), a phosphono group (-PO (OH) _2), an alkyl group which may be substituted with a carboxyl group, an alkenyl group which may be substituted with a carboxyl group, optionally substituted by a carboxyl group Substituted by good alkoxy group, alkanoyl group, alkoxycarbonyl group, alkylsulfonyl group optionally substituted by carboxyl group, substituted or unsubstituted amino group, substituted or unsubstituted carbamoyl group, or substituted or unsubstituted sulfamoyl group May be)
Optionally substituted with a substituent selected from:
(4) Cycloalkyl group, cycloalkyloxy group, cycloalkylthio group, cycloalkylsulfinyl group, cycloalkylsulfonyl group, cycloalkenyl group, cycloalkenyloxy group, saturated or unsaturated aliphatic heterocyclic group, saturated or unsaturated Aliphatic heterocyclic oxy group, saturated or unsaturated aliphatic heterocyclic thio group, saturated or unsaturated aliphatic heterocyclic sulfinyl group, saturated or unsaturated aliphatic heterocyclic sulfonyl group, aryl group, aryloxy group An arylthio group, an arylsulfonyl group, an arylsulfinyl group, a heteroaryl group, a heteroaryloxy group, a heteroarylthio group, a heteroarylsulfonyl group, a heteroarylsulfinyl group (groups of this group include a halogen atom, a hydroxyl group, a carboxyl group, Formyl group, cyano group, sulfo (-SO ₂ OH), a phosphono group (-PO (OH) _2), an alkyl group which may be substituted with a carboxyl group, an alkenyl group which may be substituted with a carboxyl group, an alkoxy group, an alkanoyl group, an alkoxycarbonyl A group, a substituted or unsubstituted amino group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted sulfamoyl group)
May be substituted with the same or different 1 to 5 substituents selected from ];
(Xiii) cycloalkyl group, cycloalkenyl group, cycloalkyloxy group, cycloalkylcarbonyl group, cycloalkylthio group, cycloalkylsulfinyl group, cycloalkylsulfonyl group, cycloalkenyl group, cycloalkenyloxy group, saturated or unsaturated fat Aromatic heterocyclic group, saturated or unsaturated aliphatic heterocyclic oxy group, saturated or unsaturated aliphatic heterocyclic carbonyl group, saturated or unsaturated aliphatic heterocyclic thio group, saturated or unsaturated aliphatic heterocyclic ring Sulfinyl group, saturated or unsaturated aliphatic heterocyclic sulfonyl group [groups of this group are the following (1) to (3):
(1) Halogen atom, hydroxyl group, carboxyl group, formyl group, oxo group, thioxo group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH) ₂ );
(2) an alkoxy group, an alkoxycarbonyl group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, an amino group optionally substituted with the same or different 1 or 2 alkyl groups, and the same or different 1 or 2 alkyls A carbamoyl group which may be substituted with a group, a sulfamoyl group which may be substituted with one or two alkyl groups which are the same or different (groups in this group are a halogen atom, a hydroxyl group, a carboxyl group, an alkoxy group, an alkoxycarbonyl group) A group, an amino group optionally substituted with the same or different 1 or 2 alkyl groups, and an optionally substituted carbamoyl group optionally substituted with 1 or 2 alkyl groups);
(3) Cycloalkyl group, cycloalkyloxy group, cycloalkenyl group, cycloalkenyloxy group, saturated or unsaturated aliphatic heterocyclic group, saturated or unsaturated aliphatic heterocyclic oxy group, aryl group, aryloxy group , Arylthio group, arylsulfonyl group, heteroaryl group, heteroaryloxy group, heteroarylthio group, heteroarylsulfonyl group (groups in this group are halogen atom, hydroxyl group, carboxyl group, alkyl group, alkoxy group, the same or different An amino group which may be substituted with 1 or 2 alkyl groups, a carbamoyl group which may be substituted with the same or different 1 or 2 alkyl groups, a substituted with 1 or 2 alkyl groups which are the same or different Optionally substituted with a sulfamoyl group);
May be substituted with the same or different 1 to 5 substituents selected from ];
(Xiv) aryl group, aryloxy group, arylthio group, arylsulfonyl group, aroyl group, aryloxycarbonyl group, arylsulfinyl group, heteroaryl group, heteroaryloxy group, heteroarylthio group, heteroarylsulfonyl group, heteroaryl A carbonyl group, a heteroaryloxycarbonyl group, a heteroarylsulfinyl group [these groups are represented by the following (1) to (3):
(1) Halogen atom, hydroxyl group, carboxyl group, cyano group, nitro group, formyl group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH) ₂ );
(2) an alkyl group, an alkoxy group, an alkylthio group, an alkylsulfonyl group, an alkylsulfinyl group, an alkoxycarbonyl group, an amino group which may be substituted with the same or different 1 or 2 alkyl groups, the same or different 1 or 2 A carbamoyl group which may be substituted with one alkyl group, a sulfamoyl group which may be substituted with the same or different one or two alkyl groups (groups of this group are halogen atoms, hydroxyl groups, carboxyl groups, alkoxy groups, An alkoxycarbonyl group, an amino group optionally substituted with the same or different 1 or 2 alkyl groups, an optionally substituted carbamoyl group optionally substituted with 1 or 2 alkyl groups );
(3) Cycloalkyl group, cycloalkenyl group, cycloalkenyloxy group, saturated or unsaturated aliphatic heterocyclic group, saturated or unsaturated aliphatic heterocyclic oxy group, aryl group, aryloxy group, arylthio group, aryl Sulfonyl group, heteroaryl group, heteroaryloxy group, heteroarylthio group, heteroarylsulfonyl group (groups in this group are halogen atom, hydroxyl group, carboxyl group, carbamoyl group, alkyl group, alkoxy group, alkylsulfonyl group, the same Or an amino group which may be substituted with different 1 or 2 alkyl groups, a carbamoyl group which may be substituted with the same or different 1 or 2 alkyl groups, or 1 or 2 alkyl groups which are the same or different Optionally substituted with an optionally substituted sulfamoyl group )
May be substituted with the same or different 1 to 5 substituents selected from ].

  Or, “aryl group”, “heteroaryl group”, “aralkyl group”, “heteroaralkyl group”, “aryloxy group”, “aroyl group”, “aryloxycarbonyl group”, “arylthio group”, “arylsulfinyl” Group "," arylsulfonyl group "," heteroaryloxy group "," heteroarylcarbonyl group "," heteroaryloxycarbonyl group "," heteroarylthio group "," heteroarylsulfinyl group "," heteroarylsulfonyl group " ”,“ Aralkyloxy group ”,“ aralkylcarbonyl group ”,“ aralkyloxycarbonyl group ”,“ aralkylsulfonyl group ”,“ heteroaralkyloxy group ”,“ heteroaralkylcarbonyl group ”,“ heteroaralkyloxycarbonyl group ”, or "Hetero Aralkyl Kills By bonding two adjacent substituents of group ", the following formulas (T1) ~ (T18):

〔式中、Ｒ^Tは、存在しないか、１つまたは複数存在し、各々独立して、以下の(1)〜(3)：
(1)ハロゲン原子、水酸基、オキソ基、カルボキシ基、同一もしくは異なる１又は２個の置換基で置換されていてもよいカルバモイル基、飽和の脂肪族ヘテロ環オキシカルボニル基；
(2)アルキル基、アルコキシカルボニル基、アルコキシ基
（この群の基は、ハロゲン原子、カルボキシル基又はアルコキシ基で置換されていてもよい）；
(3)２つのＲ^Tが一緒になってメチレン、エチレン、トリメチレン、テトラメチレンもしくはブテニレンを表し、環を構成する１つまたは２つの炭素原子と結合し新たな環を形成する場合；
のいずれかを表し、Ｒ^xは水素原子またはアルキル基を表す。〕
で表わされる二価基を表していてもよい。
ここで、前記「飽和の脂肪族ヘテロ環オキシカルボニル基」における「飽和の脂肪族ヘテロ環」としては、例えば、酸素原子、窒素原子および／または硫黄原子を１または２個有する、５又は６員の飽和の脂肪族ヘテロ環が挙げられる。飽和の脂肪族ヘテロ環オキシカルボニル基として、例えばテトラヒドロフラニルオキシカルボニル基、テトラヒドロピラニルオキシカルボニル基、ジヒドロフラニルオキシカルボニル基、テトラヒドロチオピラニルオキシカルボニル基、テトラヒドロジオキソチオピラニルオキシカルボニル基、ピロリジニルオキシカルボニル基、ピペリジルオキシカルボニル基、ピペラジルオキシカルボニル基、イミダゾリジニルオキシカルボニル基、オキサゾリジニルオキシカルボニル基、又はチアゾリジニルオキシカルボニル基が挙げられる。

[In the formula, R ^T does not exist, or one or a plurality thereof exist, and each independently represents the following (1) to (3):
(1) a halogen atom, a hydroxyl group, an oxo group, a carboxy group, a carbamoyl group which may be substituted with the same or different one or two substituents, a saturated aliphatic heterocyclic oxycarbonyl group;
(2) an alkyl group, an alkoxycarbonyl group, an alkoxy group (a group in this group may be substituted with a halogen atom, a carboxyl group or an alkoxy group);
(3) When two R ^T together represent methylene, ethylene, trimethylene, tetramethylene or butenylene and combine with one or two carbon atoms constituting the ring to form a new ring;
^Rx represents a hydrogen atom or an alkyl group. ]
The divalent group represented by may be represented.
Here, as the “saturated aliphatic heterocycle” in the “saturated aliphatic heterocycle oxycarbonyl group”, for example, 5 or 6-membered having 1 or 2 oxygen atom, nitrogen atom and / or sulfur atom And a saturated aliphatic heterocycle. As saturated aliphatic heterocyclic oxycarbonyl group, for example, tetrahydrofuranyloxycarbonyl group, tetrahydropyranyloxycarbonyl group, dihydrofuranyloxycarbonyl group, tetrahydrothiopyranyloxycarbonyl group, tetrahydrodioxothiopyranyloxycarbonyl group, Examples include pyrrolidinyloxycarbonyl group, piperidyloxycarbonyl group, piperazyloxycarbonyl group, imidazolidinyloxycarbonyl group, oxazolidinyloxycarbonyl group, and thiazolidinyloxycarbonyl group.

Examples of the substituent in the substituted amino group, substituted carbamoyl group, substituted thiocarbamoyl group, and substituted sulfamoyl group include the following (1) to (3):
(1) alkyl group, alkylcarbonyl group, alkoxycarbonyl group, alkylsulfonyl group, alkenyl group
[This group is based on the following (a) or (b):
(a) Halogen atom, hydroxyl group, carboxyl group, oxo group, alkoxy group, alkoxycarbonyl group, alkylthio group, alkylsulfinyl group, alkylsulfonyl group, sulfo group (—SO ₂ OH), phosphono group (—PO (OH) ₂ ), An amino group optionally substituted with the same or different 1 or 2 alkyl groups, and a carbamoyl group optionally substituted with the same or different 1 or 2 alkyl groups;
(b) a cycloalkyl group, a cycloalkyloxy group, a cycloalkylthio group, a cycloalkylsulfonyl group, a cycloalkenyl group, a cycloalkenyloxy group, a saturated or unsaturated aliphatic heterocyclic group, and a saturated or unsaturated aliphatic heterocyclic ring Oxy group, saturated or unsaturated aliphatic heterocyclic thio group, saturated or unsaturated aliphatic heterocyclic sulfonyl group, aryl group, aryloxy group, arylthio group, arylsulfonyl group, aralkyl group, heteroaryl group, heteroaryl An oxy group, a heteroarylthio group, a heteroarylsulfonyl group, a heteroaralkyl group (groups of this group are substituted with a halogen atom, a hydroxyl group, a carboxyl group, a cyano group, an alkyl group which may be substituted with a carboxyl group, or a carboxyl group) An optionally substituted alkoxy group, the same or different 1 or An amino group which may be substituted with one alkyl group, a carbamoyl group which may be substituted with the same or different 1 or 2 alkyl groups, a substituent which may be substituted with 1 or 2 alkyl groups which are the same or different May be substituted with a good sulfamoyl group)
Optionally substituted with a group selected from
(2) Aryl group, heteroaryl group, aralkyl group, heteroaralkyl group, cycloalkyl group, aroyl group, heteroarylcarbonyl group, aralkylcarbonyl group, heteroaralkylcarbonyl group, cycloalkylcarbonyl group, aryloxycarbonyl group, heteroaryl Oxycarbonyl group, aralkyloxycarbonyl group, heteroaralkyloxycarbonyl group, cycloalkyloxycarbonyl group, arylsulfonyl group, heteroarylsulfonyl group, aralkylsulfonyl group, heteroaralkylsulfonyl group, cycloalkylsulfonyl group, saturated or unsaturated fat Aromatic heterocyclic group, saturated or unsaturated aliphatic heterocyclic carbonyl group, saturated or unsaturated aliphatic heterocyclic oxycarbonyl group, saturated or unsaturated aliphatic heterocyclic sulfonyl group Group [group this group, the following (a) or (b):
(a) halogen atom, hydroxyl group, carboxyl group, cyano group, nitro group;
(b) an alkyl group, an alkoxy group, an alkoxycarbonyl group, an alkylsulfonyl group, an amino group which may be substituted with the same or different 1 or 2 substituents, and a substituted with the same or different 1 or 2 alkyl groups A carbamoyl group which may be substituted and a sulfamoyl group which may be substituted with the same or different one or two alkyl groups (groups of this group are a halogen atom, a hydroxyl group, a carboxyl group, an alkoxy group, an alkoxycarbonyl group, an alkylsulfonyl group) A group, an aryl group, an amino group optionally substituted with the same or different 1 or 2 alkyl groups, or a carbamoyl group optionally substituted with the same or different 1 or 2 alkyl groups Also good)
May be substituted with the same or different 1 to 5 substituents selected from ];
(3) Two substituents are bonded to form an alkylene having 2 to 6 carbon atoms which may be substituted with a carboxy group, a hydroxyl group, an alkyl group, an alkoxy group or an alkoxycarbonyl group, Any —CH ₂ — may be replaced by a divalent group selected from —O—, —NR ²⁰ —, —SO—, —SO ₂ —, —S— and —CO—, wherein R ²⁰ is the following (a) or (b):
(a) a hydrogen atom,
(b) an alkyl group, an alkoxycarbonyl group, an alkylcarbonyl group or an alkylsulfonyl group (the group in this group is a hydroxyl group, an alkoxy group, a carboxyl group, an amino group optionally substituted with one or two different alkyl groups, And optionally substituted with the same or different carbamoyl group optionally substituted with 1 or 2 alkyl groups)
Represents];
And may be substituted with the same or different 1 or 2 substituents.

R ^{1 in} formula (1) is preferably a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, a substituted or unsubstituted group Examples include a cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, an alkyl group substituted with a substituted or unsubstituted cycloalkyl group, and an alkyl group substituted with a substituted or unsubstituted cycloalkenyl group. A substituted benzyl group, an alkyl group of carbon chain 1 substituted with a substituted or unsubstituted cycloalkyl group, that is, a methyl group substituted with a substituted or unsubstituted cycloalkyl group is particularly preferred. In addition, the substituted aryl group, the substituted heteroaryl group, the substituted aralkyl group, the substituted heteroaralkyl group, the substituted cycloalkyl group, the substituted cycloalkenyl group, the alkyl group substituted with the substituted cycloalkyl group, and the substituted cycloalkenyl group are substituted. Preferred examples of the substituent for the alkyl group include a halogen atom, an alkyl group, and an alkoxy group.

The “alkyl group” for R ² in formula (1) is preferably a linear or branched alkyl group having 1 to 4 carbon atoms. Specific examples include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, or a tert-butyl group.
The “cycloalkyl group” in R ² is preferably a 3- to 6-membered cycloalkyl group. Specific examples include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.
The “aralkyl group” in R ² is preferably a linear or branched alkyl group having 1 to 3 carbon atoms substituted with a phenyl group. Specific examples include a benzyl group (phenylmethyl group), a phenethyl group (2-phenylethyl group), or a 3-phenylpropyl group.
The “heteroaralkyl group” in R ² is preferably a linear or branched alkyl group having 1 to 3 carbon atoms substituted with a heteroaryl group, and the bonding position of the heteroaryl group and the alkyl group Is not particularly limited as long as it is chemically stable. Specifically, 2-pyridylmethyl group, 3-pyridylmethyl group, 4-pyridylmethyl group, 2-furylmethyl (furfuryl group), 3-furylmethyl group, 2-thienylmethyl group, 3-thienylmethyl group, A 2-pyridylethyl group, a 3-pyridylethyl group, a 4-pyridylethyl group, and the like can be given.
Examples of the “alkanoyl group” in R ² include a linear or branched alkanoyl group having 2 to 4 carbon atoms. Specific examples include an acetyl group, a propionyl group, a butyryl group, and an isobutyryl group.
Examples of the “alkoxycarbonyl group” for R ² include linear or branched alkoxycarbonyl groups having 2 to 4 carbon atoms. Specific examples include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, and an isopropoxycarbonyl group.
The “carbamoyl group optionally substituted with an alkyl group” in R ² is the same or different 1 or 2 alkyl group having 1 to 3 carbon atoms (methyl group, ethyl group, propyl group, or isopropyl group). And a carbamoyl group which may be substituted with.
R ² is preferably a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms, a substituted or unsubstituted alkoxycarbonyl group having 2 to 4 carbon atoms, or a substituted or unsubstituted aryl group. . R ² is particularly preferably a hydrogen atom.

In the formula ^{(1), -W 4 = W} 5 -W 6 = W 7 - as preferably, formula ^{(a): - CR 4 =} CR 5 -CR 6 = CR 7 - ( wherein, R ^4, R ⁵ , R ⁶ and R ⁷ are independently the same or different and each represents a group represented by the formula: -EA, and formula (d): -CR ⁴ = CR ⁵ -N = CR ⁷ -(In formula, R < ⁴ >, R < ⁵ > and R < ⁷ > are respectively independently the same or different and represent group | formula: -EA).
In the formula: -EA, E represents the following formulas 1) to 14):
1) -C (R ¹⁶ ) R ^17- ,
2) -O-,
3) -S (= O) m-,
4) -S (= O) ₂ NR ^16- ,
5) -C (= O)-,
6) -C (= O) O-,
7) -C (= O) NR ^16- ,
8) −C (= NR ¹⁶ ) NR ¹⁷ −,
9) -NR ^16- ,
^{10) -N (R 16) C} (= O) -,
11) -N (R ¹⁶ ) S (= O) _2- ,
^{12) -N (R 16) C} (= O) N (R 17) -,
^{13) -N (R 16) S} (= O) 2 N (R 17) -,
14) -P (= O) (OR ¹⁶ ) _2-
(Wherein, R ¹⁶ and R ¹⁷ are each independently either hydrogen atom, or a number of carbon atoms represents 1-3 alkyl group, or Formula 8), 12) in and 13), and R ¹⁶ R ¹⁷ may be bonded to represent an alkylene group having 2 to 4 carbon atoms. m represents 0, 1, or 2. )
Is bonded to the right side of the divalent group represented by formulas 1) to 14).
In this specification, when a divalent group is a different compound depending on in which direction it is bonded, it means that it is bonded in the direction represented by the structural formula unless otherwise specified.
In the formulas 1), 4) and 7) to 14), the “alkyl group having 1 to 3 carbon atoms” in R ¹⁶ and R ¹⁷ is a linear or branched carbon group having 1 to 3 carbon atoms. Represents an alkyl group, and specific examples include a methyl group, an ethyl group, a propyl group, and an isopropyl group.
Equation 8), 12) in and 13), if by bonding R ¹⁶ and R ¹⁷ represents an alkylene group having 2 to 4 carbon atoms, a divalent group of formula 8), 12) and Formula 13), detail Specifically, formulas (R1) to (R9):

を挙げることができる。

Can be mentioned.

^{-W 4 = W 5 -W 6 =} W 7 - in the formula ^{(a): - CR 4 =} CR 5 -CR 6 = CR 7 - as preferably a group represented by the formula: -CH = CH-C ( -E-A) = CH- groups represented by and among them the formula: -CH = CH-C (NO 2) = CH-, or formula: -CH = CH-C (CN ) = CH- in The groups represented are particularly preferred. The group represented by the formula (d): -CR ⁴ = CR ⁵ -N = CR ⁷ -in -W ⁴ = W ⁵ -W ⁶ = W ⁷ -is preferably the formula: -CH = CR ^5-. A group represented by N═CR ⁷ — is exemplified. That is, as a preferred embodiment of the compound of formula (1), formula (2), formula (3) or formula (4):

で表される化合物を挙げることができる。式（４）において、Ｒ⁵及びＲ⁷としては、各々独立して同一又は異なってハロゲン原子が特に好ましい。

The compound represented by these can be mentioned. In the formula (4), the R ⁵ and R ^7, particularly preferably a halogen atom independently same or different and.

In Formula (1), R ⁸ is preferably a hydrogen atom.

As the “alkyl group having 1 to 6 carbon atoms substituted with one or more halogen atoms” in R ^9, linear or branched carbon substituted with 1 to 7 identical or different halogen atoms An alkyl group having 1 to 6 atoms (specifically, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group) , Tert-pentyl group, 1-methylbutyl group, or hexyl group). Preferred examples of the halogen atom include a fluorine atom or a chlorine atom.
The “cycloalkyl group having 3 to 6 carbon atoms substituted with one or more halogen atoms” in R ⁹ is a 3 to 6-membered saturated cyclohexane substituted with 1 to 5 identical or different halogen atoms. An alkyl group (specifically, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, or a cyclohexyl group can be given). The halogen atom is preferably a fluorine atom or a chlorine atom.
R ⁹ is preferably an alkyl group having 1 to 3 carbon atoms substituted with 1 to 5 identical or different halogen atoms, and particularly preferably a trifluoromethyl group.

R ¹⁰ is preferably a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted aralkyl group, substituted or unsubstituted Unsubstituted heteroaralkyl group, alkyl group substituted with a substituted or unsubstituted saturated or unsaturated aliphatic heterocycle, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted Saturated or unsaturated aliphatic heterocycle, substituted or unsubstituted aralkylcarbonyl group, substituted or unsubstituted heteroaralkylcarbonyl group, alkylcarbonyl group substituted with substituted or unsubstituted saturated or unsaturated aliphatic heterocycle A substituted or unsubstituted arylcarbonyl group Substituted or unsubstituted heteroarylcarbonyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic carbonyl, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted Alkylsulfonyl group substituted by saturated or unsaturated aliphatic heterocycle, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocycle Examples include sulfonyl, a substituted or unsubstituted carbamoyl group, a substituted or unsubstituted sulfamoyl group, and a substituted or unsubstituted thiocarbamoyl group. As R ^10, more preferably, substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, a substituted or unsubstituted, saturated or alkyl group substituted by unsaturated aliphatic heterocycle, a substituted or unsubstituted Aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic ring, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted An alkylsulfonyl group substituted by a substituted saturated or unsaturated aliphatic heterocycle, a substituted or unsubstituted arylsulfonyl group, a substituted or unsubstituted heteroarylsulfonyl group, or a substituted or unsubstituted saturated or unsaturated fat The group heterocyclic sulfonyl.

The compound of the present invention represented by the formula (1) is appropriately combined with known methods from methods shown in the following production methods 1 to 10, methods similar to the following production methods, or synthesis methods well known to those skilled in the art. Can be manufactured. In this specification, the following abbreviations may be used for simplification of description.
Boc: tert-butoxycarbonyl group Cbz: benzyloxycarbonyl group TMS: trimethylsilyl group TBS: tert-butyldimethylsilyl group SEM: 2-[(trimethylsilyl) ethoxy] methyl group Ac: acetyl group Me: methyl group Et: ethyl group Pr : Propyl group i-Pr: isopropyl group Bu: butyl group i-Bu: isobutyl group t-Bu: tert-butyl group Ph: phenyl group Bn: benzyl group Ms: methanesulfonyl group TFA: trifluoroacetic acid Alloc: allyloxycarbonyl Base

[Production method 1]
Among the compounds represented by formula (1), the compound represented by formula (1-10) or formula (1-7) or a salt thereof is produced, for example, by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁸、Ｒ⁹、及びＲ¹⁰は、前記と同義である。Ｒ^18a、Ｒ^18bは、各々独立して、水素原子、メチル基、エチル基を表す。Ｘは、脱離基（例えば、ヨウ素原子、臭素原子、塩素原子、メタンスルホニルオキシ、トリフルオロメタンスルホニルオキシ、ｐ−トルエンスルホニルオキシ等）を表す。]
１）工程１
化合物（１−３）は、公知または公知の合成法により得られる縮合ピロール化合物（１−１）と化合物（１−２）を、不活性溶媒中、塩基と反応させることにより製造される。化合物（１−２）の使用量としては、化合物（１−１）に対して、通常１当量〜過剰量の範囲から選択される。不活性溶媒としては、例えば、エーテル系溶媒（テトラヒドロフラン、ジエチルエーテル、１，２−ジメトキシエタン、１，４−ジオキサン等）、非プロトン性極性溶媒（Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、ジメチルスルホキシド、アセトニトリル等）、ケトン類（アセトン等）、またはこれらの混合溶媒等が挙げられる。
塩基としては、例えば炭酸アルカリ(炭酸セシウム、炭酸カリウム、炭酸ナトリウム、炭酸水素カリウム、炭酸水素ナトリウム等)、水素化アルカリ（水素化ナトリウム、水素化カリウム等）、水酸化アルカリ(水酸化カリウム、水酸化ナトリウム等)、アルカリアルコキシド（ナトリウムエトキシド、ナトリウムtert-ブトキシド、カリウムtert-ブトキシド等）、有機塩基（Ｎ-メチルモルホリン、トリエチルアミン、ジイソプロピルエチルアミン、トリブチルアミン、１，８-ジアザビシクロ[５．４．０]ウンデカ-７-エン，１，５-ジアザビシクロ[４．３．０]ノナ-５-エン、１，４-ジアザビシクロ[５．４．０]ウンデカ-７-エン、ピリジン等）が挙げられ、好適には、炭酸カリウム、カリウムtert-ブトキシド、トリエチルアミン等が挙げられる。塩基の使用量としては、化合物（１−１）に対して通常１〜５当量の範囲から選択される。反応温度としては、約−７８℃〜約１５０℃の範囲から選択することができる。
２）工程２
化合物（１−７）は、化合物（１−４）と化合物（１−５）もしくは化合物（１−６）から調製される化合物を、不活性溶媒中、ルイス酸存在下、文献（例えばJournal of Fluorine Chemistry, 108, 83 (2001)、Journal of Fluorine Chemistry, 116, 103 (2002)、Tetrahedron Asymmetry, 12, 2121 (2001)）に従い、工程１で得られた化合物（１−３）と反応させることで得られる。不活性溶媒としては、例えば、エーテル系溶媒（テトラヒドロフラン、ジエチルエーテル、１，２−ジメトキシエタン、１，４−ジオキサン等）、ハロゲン化炭化水素類（ジクロロメタン、クロロホルム、１，２−ジクロロエタン、クロロベンゼン等）またはこれらの混合溶媒等が挙げられる。ルイス酸としては、塩化アルキルアルミニウム、塩化アルミニウム、四塩化チタン、四塩化スズ、塩化亜鉛、スカンジウムトリフルオロメタンスルフォネート等の金属ハロゲン化物、金属トリフラート、トリフルオロボランジエチルエーテル錯体、ヨウ化亜鉛を用いることができる。
３）工程３
化合物（１−１０）は、化合物（１−８）と化合物（１−５）もしくは化合物（１−６）から調製される化合物を用い、工程２と同様の方法により製造することができる。
４）工程４
製造法１記載の工程３と同様の方法によって、化合物（１−１）から、化合物（１−９）は製造される。
５）工程５
製造法１記載の工程１と同様の方法によって、工程４で得られた化合物（１−９）から、化合物（１−１０）を製造することもできる。
６）工程６
製造法１記載の工程２と同様の方法によって、化合物（１−１）から、化合物（１−１１）は製造される。
７）工程７
製造法１記載の工程１と同様の方法によって、工程６で得られた化合物（１−１１）から、化合物（１−７）を製造することができる。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 8, R 9, and R ¹⁰ are as defined above. R ^18a and R ^18b each independently represent a hydrogen atom, a methyl group, or an ethyl group. X represents a leaving group (for example, iodine atom, bromine atom, chlorine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, etc.). ]
1) Step 1
Compound (1-3) is produced by reacting a condensed pyrrole compound (1-1) obtained by a known or known synthesis method with compound (1-2) with a base in an inert solvent. The amount of compound (1-2) to be used is usually selected from the range of 1 equivalent to excess with respect to compound (1-1). Examples of the inert solvent include ether solvents (tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane, etc.), aprotic polar solvents (N, N-dimethylformamide, N, N-dimethyl). Acetamide, dimethyl sulfoxide, acetonitrile, etc.), ketones (acetone, etc.), or a mixed solvent thereof.
Examples of the base include alkali carbonate (cesium carbonate, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc.), alkali hydride (sodium hydride, potassium hydride, etc.), alkali hydroxide (potassium hydroxide, water, etc.) Sodium oxide, etc.), alkali alkoxide (sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, etc.), organic base (N-methylmorpholine, triethylamine, diisopropylethylamine, tributylamine, 1,8-diazabicyclo [5.4. 0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [5.4.0] undec-7-ene, pyridine and the like. Preferable examples include potassium carbonate, potassium tert-butoxide, triethylamine and the like. The amount of the base used is usually selected from the range of 1 to 5 equivalents relative to compound (1-1). The reaction temperature can be selected from the range of about −78 ° C. to about 150 ° C.
2) Step 2
Compound (1-7) is prepared by reacting compound (1-4) with compound (1-5) or compound (1-6) in the presence of a Lewis acid in an inert solvent (for example, Journal of Fluorine Chemistry, 108, 83 (2001), Journal of Fluorine Chemistry, 116, 103 (2002), Tetrahedron Asymmetry, 12, 2121 (2001)) and reacting with the compound (1-3) obtained in step 1 It is obtained by. Examples of the inert solvent include ether solvents (tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane, etc.), halogenated hydrocarbons (dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, etc.). ) Or a mixed solvent thereof. As the Lewis acid, metal halides such as alkylaluminum chloride, aluminum chloride, titanium tetrachloride, tin tetrachloride, zinc chloride, scandium trifluoromethanesulfonate, metal triflate, trifluoroborane diethyl ether complex, zinc iodide are used. be able to.
3) Step 3
Compound (1-10) can be produced in the same manner as in step 2 using the compound prepared from compound (1-8) and compound (1-5) or compound (1-6).
4) Step 4
Compound (1-9) is produced from compound (1-1) by the same method as in Step 3 described in Production Method 1.
5) Step 5
Compound (1-10) can also be produced from compound (1-9) obtained in Process 4 by the same method as in Process 1 described in Production Process 1.
6) Step 6
Compound (1-11) is produced from compound (1-1) by the same method as in Step 2 described in Production Method 1.
7) Step 7
Compound (1-7) can be produced from compound (1-11) obtained in Process 6 by the same method as in Process 1 described in Production Process 1.

[Production method 2]
Among the compounds represented by the formula (1), the compound represented by the formula (1-7) or the formula (2-5) or a salt thereof is produced, for example, by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁸、Ｒ⁹、Ｒ¹⁰、Ｒ^18a、Ｒ^18b、及びＸは、前記と同義である。Ｐrotは、アミノ基の保護基（Protective Groups in Organic Synthesis 3rd Edition (John Wiley ＆ Sons, Inc.)又はＲ¹⁰を表す。]
１）工程１
製造法１記載の工程１と同様の方法によって、化合物（１−１）から、化合物（１−３）は製造される。
２）工程２
化合物（２−１）は、工程１で得られた化合物（１−３）を、溶媒中、塩基存在下または非存在下にハロゲン化剤と反応させることにより製造される（例えばTetrahedron Letters. 43, 2695 (2002), Comprehensive Organic transformation, R. C. ラロック著, VCH publisher Inc., 1989等参照）。ハロゲン化剤としては、N-クロロスクシニルイミド、N-ブロモスクシニルイミド、N-ヨードスクシニルイミド等のN-ハロゲン化イミド類、塩素、臭素、ヨウ素等を挙げることが出来る。ハロゲン化剤の使用量としては、化合物（１−３）に対して、通常１当量〜過剰量の範囲から選択される。不活性溶媒としては、例えば、エーテル系溶媒（テトラヒドロフラン、ジエチルエーテル、１，２−ジメトキシエタン、１，４−ジオキサン等）、非プロトン性極性溶媒（Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、ジメチルスルホキシド、アセトニトリル等）、ケトン類（アセトン等）、またはこれらの混合溶媒等が挙げられる。
塩基としては、例えば炭酸アルカリ(炭酸セシウム、炭酸カリウム、炭酸ナトリウム、炭酸水素カリウム、炭酸水素ナトリウム等)、水素化アルカリ（水素化ナトリウム、水素化カリウム等）、水酸化アルカリ(水酸化カリウム、水酸化ナトリウム等)、アルカリアルコキシド（ナトリウムエトキシド、ナトリウムtert-ブトキシド、カリウムtert-ブトキシド等）、有機塩基（Ｎ-メチルモルホリン、トリエチルアミン、ジイソプロピルエチルアミン、トリブチルアミン、１，８-ジアザビシクロ[５．４．０]ウンデカ-７-エン，１，５-ジアザビシクロ[４．３．０]ノナ-５-エン、１，４-ジアザビシクロ[５．４．０]ウンデカ-７-エン、ピリジン等）が挙げられ、好適には、炭酸カリウム、カリウムtert-ブトキシド、トリエチルアミン等が挙げられる。塩基の使用量としては、化合物（１−３）に対して通常１〜５当量の範囲から選択される。反応温度としては、約−７８℃〜約１５０℃の範囲から選択することができる。
３）工程３
製造法２記載の工程２と同様の方法によって、化合物（１−１）から、化合物（２−２）は製造される。
４）工程４
製造法２記載の工程１と同様の方法によって、工程２で得られた化合物（２−２）から、化合物（１−２）は製造することもできる。
５）工程５
化合物（２−５）は、不活性溶媒中、工程２または４で得られた化合物（２−１）をハロゲン-メタル交換したのちに、化合物（２−３）及び化合物（１−６）から調整した化合物と文献（Org. Lett., 9, 683 (2007)）に従い反応させることにより、製造することができる。ハロゲン-メタル交換の方法としては、例えば、Angew. Chem. Int. Ed. 43, 3333 (2004), Angew. Chem. Int. Ed. 42, 4302 (2003), Angew. Chem. Int. Ed. 39, 4414 (2000)等の文献が挙げられる。
６）工程６
化合物（１−７）は、工程５で得られた化合物（２−５）を文献（例えばOrg. Lett., 9, 683 (2007)、Protective Groups in Organic Synthesis 3rd Edition (John Wiley ＆ Sons, Inc.）記載の方法により反応させることで、製造することができる。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 8, R 9, R 10, R 18a, R 18b, and X have the same meanings as defined above. Prot represents a protecting group for amino group (Protective Groups in Organic Synthesis 3rd Edition (John Wiley & Sons, Inc.) or R ¹⁰ )
1) Step 1
Compound (1-3) is produced from compound (1-1) by the same method as in Step 1 described in Production Method 1.
2) Step 2
Compound (2-1) is produced by reacting compound (1-3) obtained in Step 1 with a halogenating agent in a solvent in the presence or absence of a base (for example, Tetrahedron Letters. 43). , 2695 (2002), Comprehensive Organic transformation, RC Larroque, VCH publisher Inc., 1989). Examples of the halogenating agent include N-halogenated imides such as N-chlorosuccinimide, N-bromosuccinimide, and N-iodosuccinimide, chlorine, bromine, iodine and the like. The amount of the halogenating agent used is usually selected from the range of 1 equivalent to an excess amount relative to the compound (1-3). Examples of the inert solvent include ether solvents (tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane, etc.), aprotic polar solvents (N, N-dimethylformamide, N, N-dimethyl). Acetamide, dimethyl sulfoxide, acetonitrile, etc.), ketones (acetone, etc.), or a mixed solvent thereof.
Examples of the base include alkali carbonate (cesium carbonate, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc.), alkali hydride (sodium hydride, potassium hydride, etc.), alkali hydroxide (potassium hydroxide, water, etc.) Sodium oxide, etc.), alkali alkoxide (sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, etc.), organic base (N-methylmorpholine, triethylamine, diisopropylethylamine, tributylamine, 1,8-diazabicyclo [5.4. 0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [5.4.0] undec-7-ene, pyridine and the like. Preferable examples include potassium carbonate, potassium tert-butoxide, triethylamine and the like. The amount of the base used is usually selected from the range of 1 to 5 equivalents relative to the compound (1-3). The reaction temperature can be selected from the range of about −78 ° C. to about 150 ° C.
3) Step 3
Compound (2-2) is produced from compound (1-1) by the same method as in Step 2 described in Production Method 2.
4) Step 4
Compound (1-2) can also be produced from compound (2-2) obtained in Step 2 by the same method as in Step 1 described in Production Method 2.
5) Step 5
Compound (2-5) is obtained from Compound (2-3) and Compound (1-6) after halogen-metal exchange of Compound (2-1) obtained in Step 2 or 4 in an inert solvent. It can be produced by reacting the prepared compound with the literature (Org. Lett., 9, 683 (2007)). As a method of halogen-metal exchange, for example, Angew. Chem. Int. Ed. 43, 3333 (2004), Angew. Chem. Int. Ed. 42, 4302 (2003), Angew. Chem. Int. Ed. 39 , 4414 (2000).
6) Step 6
Compound (1-7) is compound (2-5) obtained in Step 5 described in literature (eg Org. Lett., 9, 683 (2007), Protective Groups in Organic Synthesis 3rd Edition (John Wiley & Sons, Inc. .) Can be produced by reacting by the method described.

[Production method 3]
Among the compounds represented by formula (1), the compound represented by formula (3-2) or a salt thereof is produced, for example, by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁸、及びＲ⁹は、前記と同義である。Ｒ¹⁹及びＲ²¹は、各々独立して、水素原子、置換もしくは無置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、または置換もしくは無置換のヘテロアラルキル基を表す。]
１）工程１
化合物（３−２）は、化合物（１−７）を、溶媒中、酸存在下または非存在下に、化合物（３−１）、還元剤と反応させることにより製造することができる。酸としては、酢酸等の有機酸や四塩化チタン等のルイス酸などが挙げられる。酸の使用量としては、化合物（１−７）に対し、通常１〜大過剰の範囲から選択される。還元剤としては、例えばシアノ水素化ホウ素ナトリウム、トリアセトキシ水素化ホウ素ナトリウム、水素化ホウ素ナトリウム、水素雰囲気下におけるパラジウム−炭素等が挙げられる。還元剤の使用量としては、化合物（１−７）に対し、通常１〜大過剰の範囲から選択される。溶媒としては、例えば、エーテル系溶媒（テトラヒドロフラン、ジエチルエーテル、１，２−ジメトキシエタン、１，４−ジオキサン等）、ハロゲン化炭化水素類（ジクロロメタン、クロロホルム、１，２−ジクロロエタン、クロロベンゼン等）、非プロトン性極性溶媒（Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、ジメチルスルホキシド、アセトニトリル等）、プロトン性極性溶媒（メタノール、エタノール等）またはこれらの混合溶媒等が挙げられる。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 8, and R ⁹ are as defined above. R ¹⁹ and R ²¹ are each independently a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, substituted or unsubstituted It represents an unsubstituted cycloalkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted heteroaralkyl group. ]
1) Step 1
Compound (3-2) can be produced by reacting compound (1-7) with compound (3-1) and a reducing agent in a solvent in the presence or absence of an acid. Examples of the acid include organic acids such as acetic acid and Lewis acids such as titanium tetrachloride. The amount of the acid used is usually selected from the range of 1 to a large excess relative to the compound (1-7). Examples of the reducing agent include sodium cyanoborohydride, sodium triacetoxyborohydride, sodium borohydride, palladium-carbon in a hydrogen atmosphere, and the like. The amount of the reducing agent to be used is usually selected from a range of 1 to a large excess relative to the compound (1-7). Examples of the solvent include ether solvents (tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane, etc.), halogenated hydrocarbons (dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, etc.), Examples include aprotic polar solvents (N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, etc.), protic polar solvents (methanol, ethanol, etc.), and mixed solvents thereof.

[Production Method 4]
Among the compounds represented by the formula (1), the compound represented by the formula (4-3) or a salt thereof is produced, for example, by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁸、及びＲ⁹は、前記と同義である。Ｒ²²は、置換もしくは無置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、置換もしくは無置換のヘテロアラルキル基、置換もしくは無置換のアルカノイル基、置換もしくは無置換のアルコキシカルボニル基、置換もしくは無置換のアルキルスルホニル基、置換もしくは無置換のアルケニルカルボニル基、置換もしくは無置換のアルケニルオキシカルボニル基、置換もしくは無置換のアルケニルスルホニル基、置換もしくは無置換のシクロアルキルカルボニル基、置換もしくは無置換のシクロアルキルオキシカルボニル基、置換もしくは無置換のシクロアルキルスルホニル基、置換もしくは無置換のアロイル基、置換もしくは無置換のアリールオキシカルボニル基、置換もしくは無置換のアリールスルホニル基、置換もしくは無置換のヘテロアリールカルボニル基、置換もしくは無置換のヘテロアリールオキシカルボニル基、置換もしくは無置換のヘテロアリールスルホニル基、置換もしくは無置換のアラルキルカルボニル基、置換もしくは無置換のアラルキルオキシカルボニル基、置換もしくは無置換のアラルキルスルホニル基、置換もしくは無置換のヘテロアラルキルカルボニル基、置換もしくは無置換のヘテロアラルキルオキシカルボニル基、置換もしくは無置換のヘテロアラルキルスルホニル基、置換もしくは無置換のカルバモイル基、置換もしくは無置換のスルファモイル基、置換もしくは無置換のチオカルバモイル基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環基、置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環カルボニル基、または置換もしくは無置換の飽和もしくは不飽和の脂肪族ヘテロ環スルホニル基を表す。]
１）工程１
化合物（４−３）は、化合物（１−７）と、溶媒中、塩基存在下もしくは非存在下に、化合物（４−１）もしくは化合物（４−２）と反応させることにより、製造することができる。塩基としては、例えば炭酸アルカリ(炭酸セシウム、炭酸カリウム、炭酸ナトリウム、炭酸水素カリウム、炭酸水素ナトリウム等)、水素化アルカリ（水素化ナトリウム、水素化カリウム等）、水酸化アルカリ(水酸化カリウム、水酸化ナトリウム等)、アルカリアルコキシド（ナトリウムエトキシド、ナトリウムtert-ブトキシド、カリウムtert-ブトキシド等）、有機塩基（Ｎ-メチルモルホリン、トリエチルアミン、ジイソプロピルエチルアミン、トリブチルアミン、１，８-ジアザビシクロ[５．４．０]ウンデカ-７-エン，１，５-ジアザビシクロ[４．３．０]ノナ-５-エン、１，４-ジアザビシクロ[５．４．０]ウンデカ-７-エン、ピリジン等）が挙げられる。塩基の使用量としては、化合物（１−７）に対し、通常１〜大過剰の範囲から選択される。溶媒としては、例えば、エーテル系溶媒（テトラヒドロフラン、ジエチルエーテル、１，２−ジメトキシエタン、１，４−ジオキサン等）、ハロゲン化炭化水素類（ジクロロメタン、クロロホルム、１，２−ジクロロエタン、クロロベンゼン等）、プロトン性極性溶媒（メタノール、エタノール等）非プロトン性極性溶媒（Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミド、ジメチルスルホキシド、アセトニトリル等）、またはこれらの混合溶媒等が挙げられる。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 8, and R ⁹ are as defined above. R ²² represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, substituted or unsubstituted Aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted alkanoyl group, substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted Substituted alkylsulfonyl group, substituted or unsubstituted alkenylcarbonyl group, substituted or unsubstituted alkenyloxycarbonyl group, substituted or unsubstituted alkenylsulfonyl group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted cycloaryl Killoxycarbonyl group, substituted or unsubstituted cycloalkylsulfonyl group, substituted or unsubstituted aroyl group, substituted or unsubstituted aryloxycarbonyl group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylcarbonyl Group, substituted or unsubstituted heteroaryloxycarbonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted aralkylcarbonyl group, substituted or unsubstituted aralkyloxycarbonyl group, substituted or unsubstituted aralkylsulfonyl group Substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted heteroaralkyloxycarbonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted Yl group, substituted or unsubstituted sulfamoyl group, substituted or unsubstituted thiocarbamoyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic ring It represents a carbonyl group or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic sulfonyl group. ]
1) Step 1
Compound (4-3) is produced by reacting compound (1-7) with compound (4-1) or compound (4-2) in a solvent in the presence or absence of a base. Can do. Examples of the base include alkali carbonate (cesium carbonate, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc.), alkali hydride (sodium hydride, potassium hydride, etc.), alkali hydroxide (potassium hydroxide, water, etc.) Sodium oxide, etc.), alkali alkoxide (sodium ethoxide, sodium tert-butoxide, potassium tert-butoxide, etc.), organic base (N-methylmorpholine, triethylamine, diisopropylethylamine, tributylamine, 1,8-diazabicyclo [5.4. 0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [5.4.0] undec-7-ene, pyridine and the like. . The amount of base used is usually selected from the range of 1 to a large excess relative to compound (1-7). Examples of the solvent include ether solvents (tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane and the like), halogenated hydrocarbons (dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene and the like), Examples include a protic polar solvent (methanol, ethanol, etc.), an aprotic polar solvent (N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, etc.), or a mixed solvent thereof.

[Production Method 5]
Among the compounds represented by the formula (1), the compound represented by the formula (1-10) or a salt thereof is produced, for example, by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁸、Ｒ⁹、Ｒ¹⁰、Ｘ、及びＰrotは、前記と同義である。]
１）工程１
文献（例えばSynlett, 1301 (1999)、有機合成化学協会誌, 59, 51 (2001)、Protective Groups in Organic Synthesis 3rd Edition (John Wiley ＆ Sons, Inc.）、Comprehensive Organic transformation,（ R. C. ラロック著, VCH publisher Inc., 1989））に記載されている方法と同様の方法によって、化合物（１−７）から化合物（５−１）を製造することができる。
２）工程２
文献（例えばSynlett, 1301 (1999)、有機合成化学協会誌, 59, 51 (2001)、Protective Groups in Organic Synthesis 3rd Edition (John Wiley ＆ Sons, Inc.）、Comprehensive Organic transformation,（ R. C. ラロック著, VCH publisher Inc., 1989））に記載されている方法と同様な方法によって、工程１で得られた化合物（５−１）から、化合物（５−３）を製造することができる。
３）工程３
文献（例えばSynlett, 1301 (1999)、有機合成化学協会誌, 59, 51 (2001)、Protective Groups in Organic Synthesis 3rd Edition (John Wiley ＆ Sons, Inc.）、Comprehensive Organic transformation,（ R. C. ラロック著, VCH publisher Inc., 1989）)に記載されている方法と同様な方法によって、工程２で得られた化合物（５−３）から、化合物（１−１０）を製造することができる。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 8, R 9, R 10, X, and Prot are as defined above. ]
1) Step 1
Literature (for example, Synlett, 1301 (1999), Journal of Synthetic Organic Chemistry, 59, 51 (2001), Protective Groups in Organic Synthesis 3rd Edition (John Wiley & Sons, Inc.), Comprehensive Organic transformation, (by RC Larock, VCH The compound (5-1) can be produced from the compound (1-7) by a method similar to the method described in publisher Inc., 1989)).
2) Step 2
Literature (for example, Synlett, 1301 (1999), Journal of Synthetic Organic Chemistry, 59, 51 (2001), Protective Groups in Organic Synthesis 3rd Edition (John Wiley & Sons, Inc.), Comprehensive Organic transformation, (by RC Larock, VCH The compound (5-3) can be produced from the compound (5-1) obtained in Step 1 by a method similar to the method described in publisher Inc., 1989)).
3) Step 3
Literature (for example, Synlett, 1301 (1999), Journal of Synthetic Organic Chemistry, 59, 51 (2001), Protective Groups in Organic Synthesis 3rd Edition (John Wiley & Sons, Inc.), Comprehensive Organic transformation, (by RC Larock, VCH The compound (1-10) can be produced from the compound (5-3) obtained in Step 2 by a method similar to the method described in publisher Inc., 1989)).

[Production Method 6]
Among the compounds represented by formula (1), the compound represented by formula (6-5) or formula (6-7) or a salt thereof is produced, for example, by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁸、Ｒ⁹、Ｒ¹⁰、Ｘ、及びＰrotは、前記と同義である。]
１）工程１
製造法１記載の工程１と同様の方法によって、化合物（１−１）から、化合物（１−３）は製造される。
２）工程２
化合物（６−３）は、工程１で得られた化合物（１−３）を、酸無水物（６−１）または酸ハロゲン化物（６−２）と、不活性溶媒中、ルイス酸もしくは塩基いずれか一方の存在下または非存在下、反応させることにより製造することができる。ルイス酸としては、塩化アルキルアルミニウム、塩化アルミニウム、四塩化チタン、四塩化スズ、塩化亜鉛、スカンジウムトリフルオロメタンスルフォネート等の金属ハロゲン化物、金属トリフラートを用いることができる。塩基としては、例えば、有機塩基（１−ヒドロキシベンズトリアゾール、Ｎ-メチルモルホリン、トリエチルアミン、ジイソプロピルエチルアミン、トリブチルアミン、１，８-ジアザビシクロ[５．４．０]ウンデカ-７-エン，１，５-ジアザビシクロ[４．３．０]ノナ-５-エン、１，４-ジアザビシクロ[５．４．０]ウンデカ-７-エン、ピリジン、ジメチルアミノピリジン、ピコリン等）、アルカリ金属（ｎ−ブチルリチウム、メチルリチウム、イソプロピルマグネシウムブロミド等）、無機塩基（ナトリウムエトキシド、ナトリウムメトキシド、カリウム tert-ブトキシド、水素化ナトリウム等）が挙げられる。塩基の使用量としては、化合物（１−３）に対し、通常１〜５当量の範囲から選択される。酸無水物（６−１）または酸ハロゲン化物（６−２）の使用量としては、化合物（１−３）に対し、通常１〜５当量の範囲から選択される。不活性溶媒としては、例えば、エーテル系溶媒（テトラヒドロフラン、ジエチルエーテル、１，２−ジメトキシエタン、１，４−ジオキサン等）、ハロゲン化炭化水素類（ジクロロメタン、クロロホルム、１，２−ジクロロエタン、クロロベンゼン等）、ニトロ化合物（ニトロメタン、ニトロエタン、ニトロベンゼン等）、またはこれらの混合溶媒等が挙げられる。反応温度としては、約−７８℃〜約１５０℃の範囲から選択することができる。
３）工程３
製造法６記載の工程２と同様の方法によって、化合物（６−４）は化合物（１−１）から製造できる。
４）工程４
製造法１記載の工程１と同様の方法によって、工程３で得られた化合物（６−４）から、化合物（６−３）を製造することもできる。
５）工程５
化合物（６−５）は、工程２または４で得られた化合物（６−３）を、ルイス酸存在下、文献（例えばTetrahedron Lett., 31, 5547 (1990)、Comprehensive Organic transformation,（ R. C. ラロック著, VCH publisher Inc., 1989））記載の方法もしくは製造法３記載の工程１と同様の方法により、化合物（１−８）と反応させることにより製造することができる。
６）工程６
化合物（６−８）は、工程２または４で得られた化合物（６−３）を文献（例えばTetrahedron Lett., 32, 987 (1991)、 Org. Lett., 7, 355 (2005) ）記載の方法に従い、化合物（２−３）と反応させることにより、製造することができる。
７）工程７
化合物（６−７）は、工程６で得られた化合物（６−６）を、文献（例えばTetrahedron Lett., 32, 987 (1991)、 Org. Lett., 7, 355 (2005)、Protective Groups in Organic Synthesis 3rd Edition (John Wiley ＆ Sons, Inc. ）、Comprehensive Organic transformation,（ R. C. ラロック著, VCH publisher Inc., 1989）)記載の方法により、還元反応及び脱保護反応をさせることで製造することができる。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 8, R 9, R 10, X, and Prot are as defined above. ]
1) Step 1
Compound (1-3) is produced from compound (1-1) by the same method as in Step 1 described in Production Method 1.
2) Step 2
Compound (6-3) is compound obtained by subjecting compound (1-3) obtained in Step 1 to acid anhydride (6-1) or acid halide (6-2) and Lewis acid or base in an inert solvent. It can be produced by reacting in the presence or absence of either one. As the Lewis acid, metal halides such as alkylaluminum chloride, aluminum chloride, titanium tetrachloride, tin tetrachloride, zinc chloride, scandium trifluoromethanesulfonate, and metal triflates can be used. Examples of the base include organic bases (1-hydroxybenztriazole, N-methylmorpholine, triethylamine, diisopropylethylamine, tributylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1,5- Diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [5.4.0] undec-7-ene, pyridine, dimethylaminopyridine, picoline, etc.), alkali metal (n-butyllithium, Methyl lithium, isopropyl magnesium bromide, etc.) and inorganic bases (sodium ethoxide, sodium methoxide, potassium tert-butoxide, sodium hydride, etc.). The usage-amount of a base is normally selected from the range of 1-5 equivalent with respect to a compound (1-3). The amount of the acid anhydride (6-1) or acid halide (6-2) used is usually selected from the range of 1 to 5 equivalents relative to the compound (1-3). Examples of the inert solvent include ether solvents (tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane, etc.), halogenated hydrocarbons (dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, etc.). ), Nitro compounds (nitromethane, nitroethane, nitrobenzene, etc.), or mixed solvents thereof. The reaction temperature can be selected from the range of about −78 ° C. to about 150 ° C.
3) Step 3
Compound (6-4) can be produced from compound (1-1) by the same method as in Step 2 described in Production Method 6.
4) Step 4
Compound (6-3) can also be produced from compound (6-4) obtained in Step 3 by the same method as in Step 1 described in Production Method 1.
5) Step 5
Compound (6-5) is obtained by reacting Compound (6-3) obtained in Step 2 or 4 in the presence of a Lewis acid in the literature (for example, Tetrahedron Lett., 31, 5547 (1990), Comprehensive Organic transformation, (RC Lalock). VCH publisher Inc., 1989))) or by the same method as in Step 1 described in Production Method 3, can be produced by reacting with compound (1-8).
6) Step 6
Compound (6-8) describes compound (6-3) obtained in Step 2 or 4 in the literature (for example, Tetrahedron Lett., 32, 987 (1991), Org. Lett., 7, 355 (2005)). According to the method, it can be produced by reacting with compound (2-3).
7) Step 7
Compound (6-7) was prepared by converting compound (6-6) obtained in Step 6 from literature (eg, Tetrahedron Lett., 32, 987 (1991), Org. Lett., 7, 355 (2005), Protective Groups. in Organic Synthesis 3rd Edition (John Wiley & Sons, Inc.), Comprehensive Organic transformation, (by RC Laroc, VCH publisher Inc., 1989)) to produce by reducing and deprotecting. Can do.

[Production method 7]
Among the compounds represented by formula (1), the compound represented by formula (7-4), formula (7-5), formula (7-7), or formula (7-8) or a salt thereof is For example, it is manufactured by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁸、Ｒ⁹、及びＲ¹⁰は、前記と同義である。Ｒ²³及びＲ²⁴は、各々独立して置換もしくは無置換のアルキル基、置換もしくは無置換のアルケニル基、置換もしくは無置換のアルキニル基、置換もしくは無置換のシクロアルキル基、置換もしくは無置換のシクロアルケニル基、置換もしくは無置換のアリール基、置換もしくは無置換のヘテロアリール基、置換もしくは無置換のアラルキル基、または置換もしくは無置換のヘテロアラルキル基を表す。]
１）工程１
化合物（７−２）は、例えばトルエン等の芳香族炭化水素系溶媒中で化合物（７−１）をクロロスルホニルイソシアナートと、文献（例えばOrg. Lett., 3, 2242 (2001)）に従い反応させることにより、製造することができる。クロロスルホニルイソシアナートの使用量としては、化合物（７−１）に対し、通常１当量〜過剰量の範囲から選択される。
２）工程２
化合物（７−３）は、工程１で得られた化合物（７−２）をジクロロメタンなどのハロゲン化炭化水素系溶媒中、４−ジメチルアミノピリジンと、文献（例えばOrg. Lett., 3, 2242 (2001)）に従い反応させることで製造することができる。４−ジメチルアミノピリジンの使用量としては、化合物（７−２）に対し、通常１当量〜過剰量の範囲から選択される。
３）工程３
化合物（７−４）は、製造法１の工程２または製造法２の工程６で得られた化合物（１−７）を、不活性溶媒中、化合物（７−３）と、文献（例えばOrg. Lett., 3, 2242 (2001)）に従い反応させることで得ることができる。不活性溶媒としては、例えば、エーテル系溶媒（テトラヒドロフラン、ジエチルエーテル、１，２−ジメトキシエタン、１，４−ジオキサン等）、ハロゲン化炭化水素類（ジクロロメタン、クロロホルム、１，２−ジクロロエタン、クロロベンゼン等）またはこれらの混合溶媒等が挙げられる。反応温度としては、０℃〜溶媒の沸点の範囲から選択することができる。
４）工程４
化合物（７−５）は、工程３で得られた化合物（７−４）を、溶媒中酸性条件下反応させることで製造することができる。溶媒としては、例えば、エーテル系溶媒（テトラヒドロフラン、ジエチルエーテル、１，２−ジメトキシエタン、１，４−ジオキサン等）、ハロゲン化炭化水素類（ジクロロメタン、クロロホルム、１，２−ジクロロエタン、クロロベンゼン等）、プロトン性溶媒（メタノール、エタノール等）またはこれらの混合溶媒等が挙げられる。酸としては、ギ酸、酢酸、トリフルオロ酢酸等の有機酸や塩酸等の無機酸が挙げられる。
５）工程５
化合物（７−７）は、工程３で得られた化合物（７−４）より、文献（例えば、Eur.J.Org.Chem., 2763 (2004)、Org.Prep. Proced. Int., 28, 127 (1996)）記載の方法で、化合物（７−６）と反応させることで製造することができる。
６）工程６
製造法７記載の工程４と同様の方法によって、工程５で得られた化合物（７−７）から、化合物（７−８）を製造することができる。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 8, R 9, and R ¹⁰ are as defined above. R ²³ and R ²⁴ each independently represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group; An alkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, or a substituted or unsubstituted heteroaralkyl group is represented. ]
1) Step 1
Compound (7-2) is obtained by reacting compound (7-1) with chlorosulfonyl isocyanate in an aromatic hydrocarbon solvent such as toluene according to literature (for example, Org. Lett., 3, 2242 (2001)). By making it, it can manufacture. The amount of chlorosulfonyl isocyanate used is usually selected from the range of 1 equivalent to an excess amount relative to compound (7-1).
2) Step 2
Compound (7-3) was prepared by combining compound (7-2) obtained in Step 1 with 4-dimethylaminopyridine in a halogenated hydrocarbon solvent such as dichloromethane and literature (for example, Org. Lett., 3, 2242). (2001)). The amount of 4-dimethylaminopyridine used is usually selected from the range of 1 equivalent to an excess amount relative to compound (7-2).
3) Step 3
Compound (7-4) was prepared by combining compound (1-7) obtained in step 2 of production method 1 or step 6 of production method 2 with compound (7-3) and literature (eg, Org) in an inert solvent. Lett., 3, 2242 (2001)). Examples of the inert solvent include ether solvents (tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane, etc.), halogenated hydrocarbons (dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, etc.). ) Or a mixed solvent thereof. The reaction temperature can be selected from the range of 0 ° C. to the boiling point of the solvent.
4) Step 4
Compound (7-5) can be produced by reacting compound (7-4) obtained in Step 3 in a solvent under acidic conditions. Examples of the solvent include ether solvents (tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, 1,4-dioxane and the like), halogenated hydrocarbons (dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene and the like), Examples thereof include a protic solvent (methanol, ethanol, etc.) or a mixed solvent thereof. Examples of the acid include organic acids such as formic acid, acetic acid and trifluoroacetic acid, and inorganic acids such as hydrochloric acid.
5) Step 5
Compound (7-7) was obtained from literature (eg, Eur. J. Org. Chem., 2763 (2004), Org. Prep. Proced. Int., 28) from compound (7-4) obtained in Step 3. , 127 (1996)) and reacting with compound (7-6).
6) Step 6
Compound (7-8) can be produced from compound (7-7) obtained in Step 5 by the same method as in Step 4 described in Production Method 7.

[Production method 8]
Among the compounds represented by the formula (1), the compound represented by the formula (1-10) or a salt thereof is produced, for example, by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁸、Ｒ⁹、Ｒ¹⁰、及びＸは、前記と同義である。]
１）工程１
化合物（１−１０）は、溶媒中、製造法１の工程２または製造法２の工程６で得られた化合物（１−７）を、触媒存在下、カップリング反応を用いて化合物（５−４）と縮合させることにより製造することができる（例えば、Palladiumu Reagents and Catalysts, Jiro Tsuji著, John Wiley ＆ Sons Ltd, 2004、Angew. Chem. Int. Ed., 42, 5400 (2003)参照）。尚、化合物（４−１）におけるＲ¹⁰としては、アリル基、ヘテロアリール基が望ましい。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 8, R 9, R 10, and X have the same meanings as defined above. ]
1) Step 1
Compound (1-10) is compound (1-7) obtained in Step 2 of Production Method 1 or Step 6 of Production Method 2 in a solvent using a coupling reaction in the presence of a catalyst. 4) (see, for example, Palladiumu Reagents and Catalysts, Jiro Tsuji, John Wiley & Sons Ltd, 2004, Angew. Chem. Int. Ed., 42, 5400 (2003)). In addition, as R < ¹⁰ > in a compound (4-1), an allyl group and heteroaryl group are desirable.

[Production Method 9]
Among the compounds represented by formula (1), the compound represented by formula (6-7) or formula (9-5) or a salt thereof is produced, for example, by the method shown below.

[式中、Ｒ¹、Ｒ²、−Ｗ⁴＝Ｗ⁵−Ｗ⁶＝Ｗ⁷−、Ｒ⁹、Ｘ、及びＰrotは、前記と同義である。Ｍは、ヘテロ元素（好ましくは、アルカリ金属、アルカリ土類金属、典型金属、珪素原子等）を表す。]
１）工程１
製造法１記載の工程１と同様の方法によって、化合物（１−１）から、化合物（１−３）は製造される。
２）工程２
化合物（９−１）は、文献（例えばEur. J. Org. Chem., 2530 (2003)、Tetrahedron 49, 4015 (1993)）記載の方法に従い、工程１で得られた化合物（１−３）を反応させることで、製造することができる。
３）工程３
製造法９記載の工程２と同様の方法によって、化合物（９−２）は、化合物（１−１）から製造することができる。
４）工程４
製造法１記載の工程１と同様の方法によって、工程３で得られた化合物（９−２）から、化合物（９−１）は製造することもできる。
５）工程５
化合物（９−３）は、工程２または４で得られた化合物（９−１）を文献（例えばJ. AM. Chem. Soc., 119, 9913 (1997)、J. Org. Chem., 64, 1278 (1999)、Angew. Chem. Int. Ed., 40, 589 (2001)）記載の方法により化合物（２−３）と反応させることで、製造することができる。
６）工程６
化合物（９−５）は、工程５で得られた化合物（９−３）を文献（例えばAngew. Chem. Int. Ed., 40, 589 (2001)、Chem. Rev., 104, 6119 (2004)、Tetrahedron, 56, 3635 (2002)）記載の方法により化合物（９−４）と反応させることで、製造することができる。
７）工程７
化合物（６−７）は、工程６で得られた化合物（９−５）を文献（例えばAngew. Chem. Int. Ed., 40, 589 (2001)、 Protective Groups in Organic Synthesis 3rd Edition (John Wiley ＆ Sons, Inc. ）記載の方法により脱保護反応をさせることで製造することができる。

^{Wherein, R 1, R 2, -W} 4 = W 5 -W 6 = W 7 -, R 9, X, and Prot are as defined above. M represents a hetero element (preferably an alkali metal, an alkaline earth metal, a typical metal, a silicon atom, etc.). ]
1) Step 1
Compound (1-3) is produced from compound (1-1) by the same method as in Step 1 described in Production Method 1.
2) Step 2
Compound (9-1) is compound (1-3) obtained in Step 1 according to the method described in the literature (for example, Eur. J. Org. Chem., 2530 (2003), Tetrahedron 49, 4015 (1993)). It can manufacture by making this react.
3) Step 3
Compound (9-2) can be produced from compound (1-1) by the same method as in Step 2 described in Production Method 9.
4) Step 4
Compound (9-1) can also be produced from compound (9-2) obtained in Step 3 by the same method as in Step 1 described in Production Method 1.
5) Step 5
Compound (9-3) is compound (9-1) obtained in Step 2 or 4 described in literature (for example, J. AM. Chem. Soc., 119, 9913 (1997), J. Org. Chem., 64). , 1278 (1999), Angew. Chem. Int. Ed., 40, 589 (2001)), and reacting with the compound (2-3).
6) Step 6
Compound (9-5) is compound (9-3) obtained in Step 5 described in literature (for example, Angew. Chem. Int. Ed., 40, 589 (2001), Chem. Rev., 104, 6119 (2004). ), Tetrahedron, 56, 3635 (2002)), and can be produced by reacting with compound (9-4).
7) Step 7
Compound (6-7) is compound (9-5) obtained in Step 6 described in literature (for example, Angew. Chem. Int. Ed., 40, 589 (2001), Protective Groups in Organic Synthesis 3rd Edition (John Wiley & Sons, Inc.) can be produced by a deprotection reaction.

The raw materials and reagents used above are commercially available compounds or can be produced from known compounds using known methods, unless otherwise specified.
In each of the above production steps, when the raw material compound of each reaction has a reaction active group such as a hydroxyl group, an amino group or a carboxyl group, these groups other than the site to be reacted are preliminarily added as necessary. The compound of interest can be obtained by protecting with an appropriate protecting group and removing the protecting group after each reaction or several reactions. As a protecting group for protecting a hydroxyl group, an amino group, a carboxyl group, etc., a usual protecting group used in the field of organic synthetic chemistry may be used, and introduction and removal of such a protecting group can be carried out according to ordinary methods. (For example, the method described in Protective Groups in Organic Synthesis, TW Greene, PGM Wuts, 3rd edition, John Wiley & Sons, Inc. (1999)).
For example, the hydroxyl protecting group includes a tert-butyldimethylsilyl group, a methoxymethyl group, a tetrahydropyranyl group, and the amino group protecting group includes a tert-butyloxycarbonyl group, a benzyloxycarbonyl group, and the like. It is done. Such a hydroxyl-protecting group can be removed by reacting in a solvent such as hydrous methanol, hydrous ethanol, hydrous tetrahydrofuran or the like in the presence of an acid such as a base, sulfuric acid or acetic acid. In the case of a tert-butyldimethylsilyl group, for example, the reaction can be carried out in a solvent such as tetrahydrofuran in the presence of tetrabutylammonium fluoride. In the case of a tert-butyloxycarbonyl group, the amino-protecting group is removed in the presence of an acid such as hydrochloric acid or trifluoroacetic acid in a solvent such as hydrous tetrahydrofuran, methylene chloride, chloroform or hydrous methanol. In the case of a benzyloxycarbonyl group, for example, it can be carried out by reacting in a solvent such as acetic acid in the presence of an acid such as hydrobromic acid.
Examples of the form of protection when protecting the carboxyl group include tert-butyl ester, ortho ester, acid amide and the like. In the case of tert-butyl ester, such removal of the protecting group is performed by, for example, reacting in a water-containing solvent in the presence of hydrochloric acid. In the case of ortho ester, for example, water-containing methanol, water-containing tetrahydrofuran, water-containing 1 In the case of acid amide, for example, in the presence of an acid such as hydrochloric acid or sulfuric acid, water is treated with an acid in a solvent such as 1,2-dimethoxyethane and subsequently with an alkali such as sodium hydroxide. The reaction can be carried out in a solvent such as hydrous methanol or hydrous tetrahydrofuran.

The compounds represented by the formula (1) include those having an optically active center, and therefore, these can be obtained as a racemate or in an optically active form when an optically active starting material is used. it can. If necessary, the racemates obtained can be physically or chemically resolved into their optical enantiomers by known methods. It can also be synthesized using known asymmetric reactions. Preferably, diastereomers are formed from the racemate by a reaction using an optically active resolving agent. Different forms of diastereomers can be resolved by known methods such as fractional crystallization.
In addition, the compound represented by the formula (1) includes those having a tautomer. Examples of tautomerism include formula (13-1) and formula (13-2).

The compound of the present invention and a prodrug thereof can be converted into a salt by mixing with a pharmaceutically acceptable acid or alkali in a solvent such as water, methanol, ethanol, and acetone. Examples of the pharmaceutically acceptable acid include inorganic acids such as hydrochloric acid, hydrobromic acid, sulfate, phosphoric acid and nitric acid, or acetic acid, propionic acid, oxalic acid, succinic acid, lactic acid, malic acid, tartaric acid and citric acid. And organic acids such as maleic acid, fumaric acid, methanesulfonic acid, p-toluenesulfonic acid, and ascorbic acid. Examples of the pharmaceutically acceptable alkali addition salt include ammonium salt, lithium salt, sodium salt, potassium salt, calcium salt, magnesium salt and the like.
The present invention also includes solvates such as a hydrate of the compound represented by the general formula (1) or a pharmaceutically acceptable salt thereof, and an ethanol solvate.

In the present invention, examples of the prodrug, that is, a compound that is metabolized by an enzyme in a living body and converted into an active ingredient includes a compound in which a carboxyl group is esterified. Specific examples of the ester include methyl ester, ethyl ester, benzyl ester, pivaloyloxymethyl ester, cilexetil, medoxomil, pivoxyl, proxetyl, and mofetil (see, for example, J. Med. Chem. 47, 2393 (2004)). Etc. These compounds can be produced according to a conventional method (for example, see J. Med. Chem. 35, 4727 (1992), WO 01/40180 etc.). Prodrugs are usually used as oral preparations. That is, when the compound of the present invention has a carboxy group or a hydroxyl group, compounds obtained by converting these groups into esters are also included in the category of the present invention.
In addition, when the compound of the present invention is metabolized by an in vivo enzyme and converted into a metabolite having a lower physiological activity, the compound can be used as an ante-drug. Ante-drug is usually used as a topical agent.

The novel condensed pyrrole derivative of the present invention, a prodrug thereof or a pharmaceutically acceptable salt thereof functions as a glucocorticoid function regulator (GR modulator) and can be used as a therapeutic or prophylactic agent for all pathological conditions involving GR. .
The “glucocorticoid function regulator” in the present invention represents a substance that activates or suppresses the function of the glucocorticoid receptor (GR). For example, a GR agonist (including a partial agonist), a GR antagonist (including a partial antagonist). Etc. Specifically, the “GR modulator” inhibits the binding of GR to known steroid (including natural and synthetic steroids) compounds such as dexamethasone and suppresses the activity of dexamethasone in vitro. / It is a substance showing an enhancing action.
Glucocorticoid function regulators can be applied to the treatment of the following various diseases in which existing steroidal anti-inflammatory drugs are clinically used. 1) Diseases that are improved by physiological hormonal effects, such as hormone deficiency in which blood cortisol levels are abnormally low due to pituitary gland failure, adrenal insufficiency, etc., adrenal enzyme deficiency or dexamethasone inhibitory hypertension via high ACTH levels; 2) Rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, polymyositis, dermatomyositis, mixed connective tissue disease, vasculitis syndrome, Behcet's disease, adult Still's disease, Sjogren's syndrome, etc. 3) Idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, aplastic anemia, erythroblastic fistula, blood phagocytic syndrome, Hodgkin disease, non-Hodgkin lymphoma, multiple myeloma, acute lymph Blood diseases such as primary leukemia, chronic lymphocytic leukemia, paroxysmal nocturnal hemoglobinuria, thrombotic thrombocytopenic purpura, retinoid syndrome, cytarabine syndrome; 4) Minimal change nephrotic syndrome, membranous nephropathy, focal glomerulosclerosis, IgA nephropathy, membranoproliferative glomerulonephritis, rapidly progressive nephritis syndrome, renal lesions associated with multiple myeloma, cloglobulinemia Nephropathy, acute interstitial nephritis, drug-induced nephropathy, etc. in infectious diseases; 5) Infectious diseases (carini pneumonia, mycoplasma pneumonia), chronic obstructive pulmonary disease, interstitial lung disease (idiopathic interstitial pneumonia) , Acute interstitial pneumonia, adult respiratory distress syndrome, nonspecific interstitial pneumonia, obstructive bronchiolitis organizing pneumonia), bronchial asthma, pulmonary eosinophilia syndrome (allergic bronchopulmonary aspergillosis, allergic) Granulomatous vasculitis, chronic eosinophilic pneumonia, acute eosinophilic pneumonia), hypersensitivity pneumonia, sarcoidosis, Goodpasture syndrome, drug-induced pneumonia, radioactive pneumonia, collagen disease, and other respiratory diseases; 6) Multiple Sclerosis, acute disseminated encephalomyelitis, severe Neuropathy associated with myasthenia, chronic inflammatory demyelinating polyneuritis, Lambert-Eaton myasthenia syndrome, HTLV-1-related myelopathy, tuberculous meningitis, central nervous lupus, vasculitis・ Tolosa-Hunt syndrome ・ Nerve sarcoidosis ・ Nerve Behcet's disease ・ Idiopathic peripheral facial palsy ・ Cerebral neuropathy such as brain edema and spinal cord injury associated with head trauma and brain tumor; 7) Thyroid crisis ・ Graves' disease Thyroiditis, thyroid diseases such as drug-induced hyperthyroidism, myxedema coma; 8) Gastrointestinal diseases such as Crohn's disease, ulcerative colitis, primary intestinal malignant lymphoma, intestinal Behcet's disease; 9) Acute hepatitis, fulminant Liver diseases such as hepatitis and autoimmune hepatitis. ; 10) Ophthalmic diseases such as allergic conjunctivitis, hay fever, spring catarrh, rejection after corneal transplantation, iritis, iridocyclitis, Vogt-Koyanagi-Harada disease, optic neuritis, etc .; 11) autoimmune blistering ( Pemphigus, pemphigoid, linear IgA bullosa, acquired epidermolysis bullosa), skin disease associated with collagen disease, neutrophilic dermatosis (Sweet disease, pyoderma gangrenosum), Weber Christian disease, Steves Johnson syndrome, toxic epidermal necrosis, cutaneous vasculitis, eczema dermatitis group, drug eruption, urticaria, polymorphic exudative erythema, nodular erythema, scleroderma, discoid lupus erythematosus, deep lupus erythematosus, cutaneous malignant lymphoma Cutaneous sarcoidosis, alopecia areata, scab hemangioma, prurigo group, palmoplantar pustulosis, psoriasis, insect bites, poisoning rash, gibber rose rash, squamous red lichen, erythroderma, hypertrophic scar, keloid, Granulomatosis / Amyloid lichen Skin diseases such as alopecia areata; 12) As a therapeutic or prophylactic agent for diseases such as osteoarthritis, gout, pseudogout, inflammation around tendons or tendons, strangulation neuropathy, orthopedics-related diseases such as disc herniation, etc. Useful.
In addition, the glucocorticoid function regulator is considered to be applied to the following disease treatments that are expected to suppress the action of glucocorticoid. 1) Cushing's syndrome and other diseases in which the blood cortisol level is high or GR is excessively activated; 2) A state of reduced immune capacity associated with HIV infection; 3) Psychiatric and neurological disorders (anxiety) Disorders, mood disorders, schizophrenia, dementia, depression / anxiety symptoms associated with various diseases, premenstrual syndrome); 4) changes associated with excessive stress state; 5) useful as a therapeutic or preventive agent for diabetes, etc. .
Moreover, the glucocorticoid function regulator of this invention can be used as a therapeutic agent and a preventive agent with respect to an inflammatory disease as a GR partial agonist.

In addition, the compound of the present invention has an immunosuppressive agent, an anti-inflammatory agent, an anti-rheumatic agent, an antithrombotic agent, an antihistamine, an antiallergic agent, a β2-stimulating agent, an ST combination, a diabetes therapeutic agent, a diabetic agent for the purpose of enhancing its effect. It can be used in combination with a drug (hereinafter abbreviated as a concomitant drug) such as a complication therapeutic agent, an antihyperlipidemic agent, an antihypertensive agent, or an antiobesity agent.
As immunosuppressants, cyclophosphamide, methotrexate, cyclosporin A, etc., as anti-inflammatory agents, indomethacin, bucillamine, etc., as antirheumatic agents, leflunomide, sulfasalazine, limacarib, etc., as antithrombotic agents, warfarin, etc. Antihistamines such as olopatadine hydrochloride, fexofenadine hydrochloride, tranilast as antiallergic agents, salbutamol sulfate as probiotics such as β2 stimulants, procaterol hydrochloride as ST combinations, cotrimoxazole, etc. as antidiabetic agents Insulin resistance improving agents (such as pioglitazone or its hydrochloride), diabetic complications treatment, antihyperlipidemic agents, antihypertensives, anti-obesity agents such as central anti-obesity agents (such as phentermine) and pancreatic lipase Inhibitors (such as orlistat).
In anticipation of an anti-inflammatory action / immunomodulatory action, the combination drug preferably includes methotrexate, indomethacin, fexofenadine hydrochloride and the like, and the antidiabetic agent preferably includes an insulin resistance improving agent and the like.
When the compound of the present invention is used in combination with a concomitant drug, the amount of these drugs used can be reduced within a safe range considering the side effects of the drug.

The compounds of the present invention, when used therapeutically, are used as pharmaceutical compositions as oral or parenteral (eg, intravenous, subcutaneous, intramuscular, topical, rectal, transdermal, or nasal, Pulmonary). Examples of dosage forms for oral administration include dosage forms such as tablets, capsules, pills, granules, powders, liquids, suspensions, etc. Examples of dosage forms for parenteral administration include , Preparations in the form of aqueous injections, oily injections, ointments, creams, lotions, aerosols, suppositories, patches and the like. These preparations can be prepared using a conventionally known technique, and can contain a nontoxic and inert carrier or excipient usually used in the pharmaceutical field.
The dose varies depending on the individual compound and the disease, age, weight, sex, symptom, route of administration, etc. of the patient, but usually for adults (50 kg body weight), The drug or a pharmaceutically acceptable salt thereof is administered at 0.1 to 1000 mg / day, preferably 1 to 300 mg / day once a day or divided into 2 to 3 times a day. It can also be administered once every few days to several weeks.
The compound of the present invention is an immunosuppressive agent, anti-inflammatory agent, anti-rheumatic agent, antithrombotic agent, antihistamine agent, antiallergic agent, β2 stimulant, ST combination, diabetes therapeutic agent, diabetic complication, for the purpose of enhancing its effect Can be used in combination with drugs (concomitant drugs) such as anti-hyperlipidemic agents, antihyperlipidemic agents, antihypertensive agents, anti-obesity agents. The administration timing of the compound of the present invention and the concomitant drug is not limited, and these may be administered simultaneously to the administration subject, or may be administered with a time difference. Moreover, it is good also as a mixture of this invention compound and a concomitant drug. The dose of the concomitant drug can be appropriately selected based on the clinically used dose. The compounding ratio of the compound of the present invention and the concomitant drug can be appropriately selected depending on the administration subject, administration route, target disease, symptom, combination and the like. For example, when the administration subject is a human, the concomitant drug may be used in an amount of 0.01 to 100 parts by weight per 1 part by weight of the compound of the present invention.

The present invention will be described in more detail below with reference to examples and test examples, but the technical scope of the present invention is not limited to these examples. In addition, the compound names shown in the following Reference Examples and Examples do not necessarily follow the IUPAC nomenclature.

Reference example 1
3- (1-amino-2,2,2-trifluoroethyl) -1H-indole-6-carbonitrile 3- (1-amino-2,2,2-trifluoroethyl) -1H-indole-6-carbonitrile

トリフルオロアセトアルデヒドエチルヘミアセタール(1.44g)に、0℃でヘキサメチルジシラザン(1.61g)を加えたのちに、50℃で3時間撹拌した。反応溶液を25℃に放冷後、６−シアノインドール(1.42g)のクロロホルム(30ml)溶液を加えた。続いてボラン トリフロリド ジメチルエーテラート(1.42g)を加えて25℃で3時間撹拌した。反応溶液に1N 塩酸を加えて酢酸エチルで抽出した。水層を飽和炭酸カリウム水溶液で中和した後に、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し、ろ過した。ろ液を減圧濃縮後、得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題の化合物(460mg)を得た。
¹H-NMR (400 MHz, CDCl₃) δ 8.58 (bs, 1H), 7.83 (d, J= 8.4 Hz, 1H), 7.75 (s, 1H), 7.53 (d, J= 1.5 Hz, 1H), 7.41 (dd, J= 8.4, 1.5 Hz, 1H), 4.82-4.73 (m, 1H).
MS (ESI+) 240（M⁺+1）

Hexamethyldisilazane (1.61 g) was added to trifluoroacetaldehyde ethyl hemiacetal (1.44 g) at 0 ° C., followed by stirring at 50 ° C. for 3 hours. The reaction solution was allowed to cool to 25 ° C., and then a solution of 6-cyanoindole (1.42 g) in chloroform (30 ml) was added. Subsequently, borane trifluoride dimethyl etherate (1.42 g) was added and stirred at 25 ° C. for 3 hours. 1N Hydrochloric acid was added to the reaction solution, and the mixture was extracted with ethyl acetate. The aqueous layer was neutralized with a saturated aqueous potassium carbonate solution and then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to give the title compound (460 mg).
¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.58 (bs, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.75 (s, 1H), 7.53 (d, J = 1.5 Hz, 1H), 7.41 (dd, J = 8.4, 1.5 Hz, 1H), 4.82-4.73 (m, 1H).
MS (ESI +) 240 (M ⁺ +1)

Reference example 2
tert-butyl [1- (6-cyano-1H-indol-3-yl) -2,2,2-trifluoroethyl] carbamate tert-butyl [1- (6-cyano-1H-indol-3-yl) -2,2,2-trifluoroethyl] carbamate

参考例１で得られた3-(1-アミノ-2,2,2-トリフルオロエチル)-1H-インドール-6-カルボニトリル(60mg)のテトラヒドロフラン(5ml)溶液に、トリエチルアミン(27mg)、ジ-TERT-ブチル ジカーボネート(59mg)、4-ジメチルアミノピリジン(5mg)を加えて25℃で8時間撹拌した。反応溶液に水を加えて酢酸エチルで抽出し、有機層を飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し、ろ過した。ろ液を減圧濃縮後、得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題の化合物(15mg)を得た。
¹H-NMR (400 MHz, CDCl₃) δ 8.58 (bs, 1H), 7.83 (d, J= 8.4 Hz, 1H), 7.75 (s, 1H), 7.53 (d, J= 1.5 Hz, 1H), 7.41 (dd, J= 8.4, 1.5 Hz, 1H), 4.82-4.73 (m, 1H).
MS (ESI+) 340（M⁺+1）

To a solution of 3- (1-amino-2,2,2-trifluoroethyl) -1H-indole-6-carbonitrile (60 mg) obtained in Reference Example 1 in tetrahydrofuran (5 ml) was added triethylamine (27 mg), -TERT-butyl dicarbonate (59 mg) and 4-dimethylaminopyridine (5 mg) were added and stirred at 25 ° C. for 8 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to give the title compound (15 mg).
¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.58 (bs, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.75 (s, 1H), 7.53 (d, J = 1.5 Hz, 1H), 7.41 (dd, J = 8.4, 1.5 Hz, 1H), 4.82-4.73 (m, 1H).
MS (ESI +) 340 (M ⁺ +1)

Example 1
tert-butyl {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} carbamate tert-butyl {1- [1- ( 4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} carbamate

参考例２で得られたtert-ブチル [1-(6-シアノ-1H-インドール-3-イル)-2,2,2-トリフルオロエチル]カルバメート(5.80g)のN,N-ジメチルホルムアミド(50ml)溶液に、炭酸カリウム(4.14g)、4−クロロベンジルクロリド(3.28mg)を加えて25℃で8時間撹拌した。反応溶液に水を加えて酢酸エチルで抽出し、有機層を飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し、ろ過した。ろ液を減圧濃縮後、得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題の化合物(7.10g)を得た。
¹H-NMR (400 MHz, CDCl₃) δ 7.73 (d, J= 8.4 Hz, 1H), 7.58 (s, 1H), 7.41 (dd, J= 8.4, 1.3 Hz, 1H), 7.38 (s, 1H), 7.33 (d, J= 8.5 Hz, 2H), 7.04 (d, J= 8.5 Hz, 2H), 5.79-5.64 (m, 1H), 5.31 (s, 2H), 5.10-4.98 (m, 1H), 1.47 (s, 9H).

N, N-dimethylformamide of tert-butyl [1- (6-cyano-1H-indol-3-yl) -2,2,2-trifluoroethyl] carbamate (5.80 g) obtained in Reference Example 2 50 ml), potassium carbonate (4.14 g) and 4-chlorobenzyl chloride (3.28 mg) were added and stirred at 25 ° C. for 8 hours. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to give the title compound (7.10 g).
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.73 (d, J = 8.4 Hz, 1H), 7.58 (s, 1H), 7.41 (dd, J = 8.4, 1.3 Hz, 1H), 7.38 (s, 1H ), 7.33 (d, J = 8.5 Hz, 2H), 7.04 (d, J = 8.5 Hz, 2H), 5.79-5.64 (m, 1H), 5.31 (s, 2H), 5.10-4.98 (m, 1H) , 1.47 (s, 9H).

Example 2
3- (1-Amino-2,2,2-trifluoroethyl) -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile 3- (1-amino-2,2,2-trifluoroethyl) -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile

実施例１で得られたtert-ブチル {1-[1-(4-クロロベンジル)-6-シアノ-1H-インドール-3-イル]-2,2,2-トリフルオロエチル}カーバメート(7.10g)に４N塩酸の1,4-ジオキサン(80ml)溶液を加えて25℃で20時間撹拌した。反応溶液を減圧濃縮後、酢酸エチルを加え、続いて飽和炭酸カリウム水溶液で中和した後に、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し、ろ過した。ろ液を減圧濃縮し表題の化合物(5.56g)を得た。
¹H-NMR (400 MHz, CDCl₃) δ 7.82 (d, J= 8.4 Hz, 1H), 7.57 (s, 1H), 7.43 (s, 1H), 7.39 (dd, J= 8.4, 1.4 Hz, 1H), 7.31 (d, J= 8.5 Hz, 2H), 7.04 (d, J= 8.5 Hz, 2H), 5.31 (s, 2H), 4.81-4.74 (m, 1H).

Tert-butyl {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} carbamate (7.10 g) obtained in Example 1 ) Was added 4N hydrochloric acid in 1,4-dioxane (80 ml) and stirred at 25 ° C. for 20 hours. After the reaction solution was concentrated under reduced pressure, ethyl acetate was added, followed by neutralization with a saturated aqueous potassium carbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure to give the title compound (5.56 g).
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.82 (d, J = 8.4 Hz, 1H), 7.57 (s, 1H), 7.43 (s, 1H), 7.39 (dd, J = 8.4, 1.4 Hz, 1H ), 7.31 (d, J = 8.5 Hz, 2H), 7.04 (d, J = 8.5 Hz, 2H), 5.31 (s, 2H), 4.81-4.74 (m, 1H).

Example 3
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(3-phenylpropyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(3-phenylpropyl) amino] ethyl} -1H-indole-6-carbonitrile

実施例２で得られた3-(1-アミノ-2,2,2-トリフルオロエチル)-1-(4-クロロベンジル)-1H-インドール-6-カルボニトリル(50mg)のテトラヒドロフラン(2ml)溶液に氷冷下3-フェニルプロピオンアルデヒド(0.018ml)、酢酸(0.008ml)、トリアセトキシ水素化ホウ素ナトリウム(58mg)を順次加え室温で26時間攪拌した。反応液を飽和重曹水に注ぎ酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、硫酸マグネシウムで乾燥し、ろ過した。ろ液を減圧濃縮し得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題化合物(56mg)を得た。
¹H-NMR (400 MHz, CDCl₃) δ 7.83 (d, J= 7.8 Hz, 1H), 7.57-7.55 (m, 1H), 7.39 (dd, J= 8.4, 1.3 Hz, 1H), 7.35 (s, 1H), 7.32 (d, J= 8.3 Hz, 2H), 7.26-7.21 (m, 2H), 7.17-7.14 (m, 1H), 7.11-7.09 (m, 2H), 7.01 (d, J= 8.3 Hz, 2H), 5.29 (s, 2H), 4.46 (q, J= 7.3 Hz, 1H), 2.71-2.56 (m, 4H), 1.85-1.79 (m, 2H).
MS (ESI+) 482（M⁺+1）

3- (1-Amino-2,2,2-trifluoroethyl) -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile (50 mg) obtained in Example 2 in tetrahydrofuran (2 ml) Under ice-cooling, 3-phenylpropionaldehyde (0.018 ml), acetic acid (0.008 ml) and sodium triacetoxyborohydride (58 mg) were successively added to the solution, and the mixture was stirred at room temperature for 26 hours. The reaction mixture was poured into saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain the title compound (56 mg).
^{1 H-NMR (400 MHz,} CDCl 3) δ 7.83 (d, J = 7.8 Hz, 1H), 7.57-7.55 (m, 1H), 7.39 (dd, J = 8.4, 1.3 Hz, 1H), 7.35 (s , 1H), 7.32 (d, J = 8.3 Hz, 2H), 7.26-7.21 (m, 2H), 7.17-7.14 (m, 1H), 7.11-7.09 (m, 2H), 7.01 (d, J = 8.3 Hz, 2H), 5.29 (s, 2H), 4.46 (q, J = 7.3 Hz, 1H), 2.71-2.56 (m, 4H), 1.85-1.79 (m, 2H).
MS (ESI +) 482 (M ⁺ +1)

Example 4
N- {1- [6-Cyano-1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} furan-3-sulfonamide N- {1- [ 6-cyano-1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} furan-3-sulfonamide

3-(1-アミノ-2,2,2-トリフルオロエチル)-1-(3-メチルベンジル)-1H-インドール-6-カルボニトリル(30mg)のピリジン(1ml)溶液に氷冷下フラン‐3-スルホニルクロライド(16mg)を加え60℃で15時間攪拌した。反応液を飽和食塩水に注ぎ酢酸エチルで抽出した。有機層を硫酸マグネシウムで乾燥し、ろ過した後ろ液を減圧濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題化合物(35mg)を得た。
¹H-NMR (400 MHz, CDCl₃) δ 7.86-7.83 (m, 1H), 7.75 (d, J= 8.3 Hz, 1H), 7.64 (s, 1H), 7.41 (dd, J= 8.3, 1.2 Hz, 1H), 7.37 (s, 1H), 7.32 (t, J= 1.7 Hz, 1H), 7.26-7.22 (m, 1H), 7.17-7.15 (m, 1H), 6.95-6.94 (m, 1H), 6.88-6.86 (m, 1H), 6.46-6.45 (m, 1H), 5.39 (t, J= 7.8 Hz, 1H), 5.27 (s, 2H), 5.13 (d, J= 7.8 Hz, 1H), 2.34 (s, 3H).
MS (ESI+) 474（M⁺+1）

To a solution of 3- (1-amino-2,2,2-trifluoroethyl) -1- (3-methylbenzyl) -1H-indole-6-carbonitrile (30 mg) in pyridine (1 ml) under ice-cooling furan- 3-sulfonyl chloride (16 mg) was added and stirred at 60 ° C. for 15 hours. The reaction mixture was poured into saturated brine and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, the filtered back solution was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain the title compound (35 mg).
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.86-7.83 (m, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.64 (s, 1H), 7.41 (dd, J = 8.3, 1.2 Hz , 1H), 7.37 (s, 1H), 7.32 (t, J = 1.7 Hz, 1H), 7.26-7.22 (m, 1H), 7.17-7.15 (m, 1H), 6.95-6.94 (m, 1H), 6.88-6.86 (m, 1H), 6.46-6.45 (m, 1H), 5.39 (t, J = 7.8 Hz, 1H), 5.27 (s, 2H), 5.13 (d, J = 7.8 Hz, 1H), 2.34 (s, 3H).
MS (ESI +) 474 (M ⁺ +1)

Reference example 3
N- (tert-butoxycarbonyl) -N- [4- (dimethylazazaniumidene) -1,4-dihydropyridin-1-ylsulfonyl] -azide

Tert-ブチルアルコール(1.04g)の塩化メチレン(10ml)溶液に氷冷下クロロスルフォニルイソシアナート(1.23ml)、4-ジメチルアミノピリジン(3.44g)を加え室温で１時間攪拌した。反応液に水を加え、クロロホルムで抽出した後有機層を硫酸マグネシウムで乾燥し、ろ過した。ろ液を減圧濃縮し、得られた残渣にアセトニトリルを加えて60℃で30分攪拌した後、氷冷して濾過することで表題の化合物(3.14g)を得た。

To a methylene chloride (10 ml) solution of Tert-butyl alcohol (1.04 g), chlorosulfonyl isocyanate (1.23 ml) and 4-dimethylaminopyridine (3.44 g) were added under ice cooling, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, acetonitrile was added to the resulting residue, and the mixture was stirred at 60 ° C. for 30 min, cooled on ice and filtered to give the title compound (3.14 g).

Example 5
tert-butyl [({1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} amino) sulfonyl] carbamate tert-butyl [ ({1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} amino) sulfonyl] carbamate

実施例２で得られた3-(1-アミノ-2,2,2-トリフルオロエチル)-1-(4-クロロベンジル)-1H-インドール-6-カルボニトリル(100mg)、参考例３で得られたN-(tert-ブトキシカルボニル)-N-[4-(ジメチルアザニウミリデン)-1,4-ジヒドロピリジン-1-イルスルホニル]-アザニド(82mg)のテトラヒドロフラン(3ml)溶液を加熱還流下17時間攪拌した。反応液を飽和食塩水に注ぎ酢酸エチルで抽出した後有機層を硫酸マグネシウムで乾燥し、ろ過した。ろ液を減圧濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題の化合物(65mg)を得た。
MS (ESI+) 543（M⁺+1）

3- (1-Amino-2,2,2-trifluoroethyl) -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile (100 mg) obtained in Example 2, A solution of the obtained N- (tert-butoxycarbonyl) -N- [4- (dimethylazaniumylidene) -1,4-dihydropyridin-1-ylsulfonyl] -azide (82 mg) in tetrahydrofuran (3 ml) was heated to reflux. Stir for 17 hours. The reaction solution was poured into saturated brine and extracted with ethyl acetate, and then the organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain the title compound (65 mg).
MS (ESI +) 543 (M ⁺ +1)

Example 6
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} sulfamide N- {1- [1- (4- chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} sulfamide

実施例５で得られたtert-ブチル [({1-[1-(4-クロロベンジル)-6-シアノ-1H-インドール-3-イル]-2,2,2-トリフルオロエチル}アミノ)スルホニル]カルバメート(65mg)のクロロホルム(1ml)溶液に４N−塩酸-ジオキサン(1ml)溶液を加え室温で15時間攪拌した。反応液を濃縮し、飽和重曹水及び酢酸エチルを加えて抽出し、有機層を飽和食塩水で洗浄後、硫酸ナトリウムで乾燥し、ろ過した。濾液を減圧濃縮し、得られた残渣を薄層クロマトグラフィーにより精製することにより表題の化合物(16mg)を得た。
¹H-NMR (400 MHz, DSMO-d₆) δ 8.16 (s, 1H), 8.13 (bs, 1H), 7.97 (s, 1H), 7.92 (d, J= 8.3 Hz, 1H), 7.45-7.39 (m, 3H), 7.28 (d, J= 8.3 Hz, 2H), 6.82 (bs, 2H), 5.52 (s, 2H), 5.38-5.35 (m, 1H).
MS (ESI+) 443（M⁺+1）

Tert-butyl [({1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} amino) obtained in Example 5 To a solution of [sulfonyl] carbamate (65 mg) in chloroform (1 ml) was added 4N-hydrochloric acid-dioxane (1 ml) solution, and the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated, extracted with saturated aqueous sodium hydrogen carbonate and ethyl acetate, and the organic layer was washed with saturated brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by thin layer chromatography to give the title compound (16 mg).
¹ H-NMR (400 MHz, DSMO-d ₆ ) δ 8.16 (s, 1H), 8.13 (bs, 1H), 7.97 (s, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.45-7.39 (m, 3H), 7.28 (d, J = 8.3 Hz, 2H), 6.82 (bs, 2H), 5.52 (s, 2H), 5.38-5.35 (m, 1H).
MS (ESI +) 443 (M ⁺ +1)

Example 7
tert-butyl benzyl [({1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} amino) sulfonyl] carbamate tert-butyl benzyl [({1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} amino) sulfonyl] carbamate

実施例５で得られたtert-ブチル [({1-[1-(4-クロロベンジル)-6-シアノ-1H-インドール-3-イル]-2,2,2-トリフルオロエチル}アミノ)スルホニル]カルバメート(70mg)のテトラヒドロフラン(3ml)溶液に氷冷下トリフェニルホスフィン(50mg)、ベンジルアルコール(0.02ml)、ジエチルアゾジカルボキシレート(0.03ml)を順次加え室温で44時間攪拌した。反応液を飽和食塩水に注ぎ酢酸エチルで抽出した後有機層を硫酸マグネシウムで乾燥し、ろ過した。ろ液を減圧濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題化合物(41mg)を得た。
¹H-NMR (400 MHz, CDCl₃) δ 9.50 (d, J= 9.3 Hz, 1H), 8.21 (s, 1H), 8.00-7.95 (m, 2H), 7.46-7.22 (m, 10H), 5.52-5.46 (m, 3H), 4.81 (d, J= 16.2 Hz, 1H), 4.59 (d, J= 16.2 Hz, 1H), 0.89 (s, 9H).

Tert-butyl [({1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} amino) obtained in Example 5 To a solution of [sulfonyl] carbamate (70 mg) in tetrahydrofuran (3 ml), triphenylphosphine (50 mg), benzyl alcohol (0.02 ml) and diethyl azodicarboxylate (0.03 ml) were successively added under ice-cooling and stirred at room temperature for 44 hours. The reaction solution was poured into saturated brine and extracted with ethyl acetate, and then the organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to obtain the title compound (41 mg).
¹ H-NMR (400 MHz, CDCl ₃ ) δ 9.50 (d, J = 9.3 Hz, 1H), 8.21 (s, 1H), 8.00-7.95 (m, 2H), 7.46-7.22 (m, 10H), 5.52 -5.46 (m, 3H), 4.81 (d, J = 16.2 Hz, 1H), 4.59 (d, J = 16.2 Hz, 1H), 0.89 (s, 9H).

Example 8
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} piperidine-1-sulfonamide N- {1- [ 1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} piperidine-1-sulfonamide

スルフリルクロライド(500mg)のジクロロメタン(10ml)溶液に、氷冷下ピペリジン(0.243ml)、トリエチルアミン(0.515ml)のジクロロメタン(3ml)溶液を加え室温で2時間攪拌した。反応液を氷水に注ぎ、クロロホルムで抽出し、有機層を飽和食塩水で洗浄後、硫酸マグネシウムで乾燥し、ろ過した。ろ液を減圧濃縮後、ピペリジン‐1-スルホニルクロライドの粗精製物を得た。実施例２で得られた3-(1-アミノ-2,2,2-トリフルオロエチル)-1-(4-クロロベンジル)-1H-インドール-6-カルボニトリルのピリジンシ(2ml)溶液に、ピペリジン‐1-スルホニルクロライド(100 mg)を室温で加え60℃で24時間攪拌した。途中ピペリジン‐1-スルホニルクロライド(50mg)を追加した。反応液を飽和食塩水に注ぎ、酢酸エチルで抽出した後有機層を硫酸マグネシウムで乾燥し、ろ過した。ろ液を減圧濃縮後し得られた残渣を薄層クロマトグラフィーで精製することにより表題の化合物(8.5mg)を得た。
¹H-NMR (400 MHz, DSMO-d₆) δ 8.69 (d, J= 9.3 Hz, 1H), 8.27 (s, 1H), 8.02-8.01 (m, 2H), 7.45-7.39 (m, 3H), 7.30 (d, J= 8.3 Hz, 2H), 5.56 (d, J= 15.4 Hz, 1H), 5.49 (d, J= 15.4 Hz, 1H), 5.36-5.33 (m, 1H), 2.70-2.65 (m, 4H), 1.07-0.99 (m, 6H).
MS (ESI+) 511（M⁺+1）

Piperidine (0.243 ml) and triethylamine (0.515 ml) in dichloromethane (3 ml) were added to a solution of sulfuryl chloride (500 mg) in dichloromethane (10 ml), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ice water and extracted with chloroform. The organic layer was washed with saturated brine, dried over magnesium sulfate, and filtered. After the filtrate was concentrated under reduced pressure, a crude product of piperidine-1-sulfonyl chloride was obtained. To a solution of 3- (1-amino-2,2,2-trifluoroethyl) -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile obtained in Example 2 in pyridine (2 ml), Piperidine-1-sulfonyl chloride (100 mg) was added at room temperature and stirred at 60 ° C. for 24 hours. On the way piperidine-1-sulfonyl chloride (50 mg) was added. The reaction solution was poured into saturated brine and extracted with ethyl acetate, and then the organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by thin layer chromatography to give the title compound (8.5 mg).
¹ H-NMR (400 MHz, DSMO-d ₆ ) δ 8.69 (d, J = 9.3 Hz, 1H), 8.27 (s, 1H), 8.02-8.01 (m, 2H), 7.45-7.39 (m, 3H) , 7.30 (d, J = 8.3 Hz, 2H), 5.56 (d, J = 15.4 Hz, 1H), 5.49 (d, J = 15.4 Hz, 1H), 5.36-5.33 (m, 1H), 2.70-2.65 ( m, 4H), 1.07-0.99 (m, 6H).
MS (ESI +) 511 (M ⁺ +1)

Example 9
1- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -3-phenylthiourea 1- {1- [1 -(4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -3-phenylthiourea

実施例２で得られた3-(1-アミノ-2,2,2-トリフルオロエチル)-1-(4-クロロベンジル)-1H-インドール-6-カルボニトリル(50mg)のテトラヒドロフラン(1ml)溶液にフェニルイソチオシアネート(0.016ml)を加え室温で15時間攪拌した。反応を減圧濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題化合物(49mg)を得た。
¹H-NMR (400 MHz, DSMO-d₆) δ 9.69 (s, 1H), 8.74 (d, J= 9.5 Hz, 1H), 8.23 (s, 1H), 8.03 (s, 1H), 7.89 (d, J= 8.3 Hz, 1H), 7.50-7.47 (m, 3H), 7.41 (d, J= 8.3 Hz, 2H), 7.33-7.29 (m, 4H), 7.14-7.10 (m, 1H), 6.97-6.93 (m, 1H), 5.55 (s, 2H).
MS (ESI+) 499（M⁺+1）

3- (1-Amino-2,2,2-trifluoroethyl) -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile (50 mg) obtained in Example 2 in tetrahydrofuran (1 ml) Phenyl isothiocyanate (0.016 ml) was added to the solution and stirred at room temperature for 15 hours. The reaction was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to give the title compound (49 mg).
¹ H-NMR (400 MHz, DSMO-d ₆ ) δ 9.69 (s, 1H), 8.74 (d, J = 9.5 Hz, 1H), 8.23 (s, 1H), 8.03 (s, 1H), 7.89 (d , J = 8.3 Hz, 1H), 7.50-7.47 (m, 3H), 7.41 (d, J = 8.3 Hz, 2H), 7.33-7.29 (m, 4H), 7.14-7.10 (m, 1H), 6.97- 6.93 (m, 1H), 5.55 (s, 2H).
MS (ESI +) 499 (M ⁺ +1)

Example 10
1- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -3-phenylurea 1- {1- [1 -(4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -3-phenylurea

実施例２で得られた3-(1-アミノ-2,2,2-トリフルオロエチル)-1-(4-クロロベンジル)-1H-インドール-6-カルボニトリル(50mg)のテトラヒドロフラン(1ml)溶液にフェニルイソシアネート(0.012ml)を加え室温で15時間攪拌した。反応を減圧濃縮し、得られた残渣をシリカゲルカラムクロマトグラフィーで精製することにより表題化合物(48mg)を得た。
¹H-NMR (400 MHz, DSMO-d₆) δ 8.52 (m, 1H), 8.23-8.22 (m, 1H), 8.00 (s, 1H), 7.03 (d, J= 8.3 Hz, 1H), 7.50-7.22 (m, 10H), 6.95-6.92 (m, 1H), 5.99-5.95 (m, 1H), 5.54 (s, 2H).
MS (ESI+) 483（M⁺+1）

3- (1-Amino-2,2,2-trifluoroethyl) -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile (50 mg) obtained in Example 2 in tetrahydrofuran (1 ml) Phenyl isocyanate (0.012 ml) was added to the solution and stirred at room temperature for 15 hours. The reaction was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography to give the title compound (48 mg).
¹ H-NMR (400 MHz, DSMO-d ₆ ) δ 8.52 (m, 1H), 8.23-8.22 (m, 1H), 8.00 (s, 1H), 7.03 (d, J = 8.3 Hz, 1H), 7.50 -7.22 (m, 10H), 6.95-6.92 (m, 1H), 5.99-5.95 (m, 1H), 5.54 (s, 2H).
MS (ESI +) 483 (M ⁺ +1)

  In the same manner as the compound of Example 3, the compounds of Examples 11 to 26 having the structural formulas shown in Tables 1 and 2 were produced.

Example 11
1- (4-chlorobenzyl) -3- {1-[(cyclohexylmethyl) amino] -2,2,2-trifluoroethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3 -{1-[(cyclohexylmethyl) amino] -2,2,2-trifluoroethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.85 (d, J = 8.3 Hz, 1H), 7.58-7.56 (m, 1H), 7.40-7.386 (m, 2H), 7.32 (d, J = 8.3 Hz , 2H), 7.03 (d, J = 8.3 Hz, 2H), 5.31 (s, 2H), 4.46 (q, J = 7.3 Hz 1H), 2.53-2.38 (m, 2H), 1.78-1.37 (m, 6H ), 1.27-1.09 (m, 3H), 0.91-0.78 (m, 2H).
MS (ESI +) 460 (M ⁺ +1)

Example 12
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(2-phenylethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(2-phenylethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.72 (d, J = 8.3 Hz, 1H), 7.55-7.54 (m, 1H), 7.35-7.29 (m, 3H), 7.26-7.18 (m, 4H) , 7.13-7.11 (m, 2H), 7.00 (d, J = 8.5 Hz, 2H), 5.27 (s, 2H), 4.49 (q, J = 7.2 Hz, 1H), 2.97-2.74 (m, 4H), 1.63 (bs, 1H).
MS (ESI +) 468 (M ⁺ +1)

Example 13
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(3-thienylmethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(3-thienylmethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.74 (d, J = 8.0 Hz, 1H), 7.58-7.57 (m, 1H), 7.39-7.24 (m, 6H), 7.04 (d, J = 8.3 Hz , 2H), 7.00-6.96 (m, 1H), 5.31 (s, 2H), 4.50 (q, J = 7.3Hz, 1H), 3.87 (d, J = 13.9 Hz, 1H), 3.79 (d, J = 13.9 Hz, 1H), 1.94 (bs, 1H).
MS (ESI +) 460 (M ⁺ +1)

Example 14
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(2-furylmethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(2-furylmethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.71 (d, J = 8.3 Hz, 1H), 7.57-7.56 (m, 1H), 7.40-7.26 (m, 5H), 7.04 (d, J = 8.3 Hz , 2H), 6.32-6.31 (m, 1H), 6.11 (d, J = 3.2 Hz, 1H), 5.31 (s, 2H), 4.51 (q, J = 7.3 Hz, 1H), 3.88 (d, J = 15.2 Hz, 1H), 3.74 (d, J = 15.2 Hz, 1H), 2.06 (bs, 1H).
MS (ESI +) 444 (M ⁺ +1)

Example 15
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(3-furylmethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(3-furylmethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.79 (d, J = 8.0 Hz, 1H), 7.58 (s, 1H), 7.39-7.26 (m, 6H), 7.04 (d, J = 8.3 Hz, 2H ), 6.32 (s, 1H), 5.31 (s, 2H), 4.54-4.49 (m, 1H), 3.73 (d, J = 13.8 Hz, 1H), 3.63 (d, J = 13.8 Hz, 1H), 1.83 (bs, 1H).
MS (ESI +) 444 (M ⁺ +1)

Example 16
3- {1-[(1-benzothien-3-ylmethyl) amino] -2,2,2-trifluoroethyl} -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile 3- {1 -[(1-benzothien-3-ylmethyl) amino] -2,2,2-trifluoroethyl} -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.86 (d, J = 7.8 Hz, 1H), 7.73-7.68 (m, 2H), 7.57 (s, 1H), 7.38-7.23 (m, 7H), 7.03 (d, J = 8.0 Hz, 2H), 5.29 (s, 2H), 4.60-4.54 (m, 1H), 4.13-4.05 (m, 2H), 2.02 (bs, 1H).
MS (ESI +) 510 (M ⁺ +1)

Example 17
1- (4-Chlorobenzyl) -3- (2,2,2-trifluoro-1-{[(5-phenyl-2-thienyl) methyl] amino} ethyl) -1H-indole-6-carbonitrile 1 -(4-chlorobenzyl) -3- (2,2,2-trifluoro-1-{[(5-phenyl-2-thienyl) methyl] amino} ethyl) -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.81 (d, J = 8.3 Hz, 1H), 7.58-7.54 (m, 3H), 7.41-7.29 (m, 7H), 7.14 (d, J = 3.4 Hz , 1H), 7.04 (d, J = 8.3 Hz, 2H), 6.79 (d, J = 3.4 Hz, 1H), 5.31 (s, 2H), 4.62 (q, J = 7.3 Hz, 1H), 4.06 (d , J = 14.5 Hz, 1H), 3.93 (d, J = 14.5 Hz, 1H), 2.09 (bs, 1H).

Example 18
1- (4-Chlorobenzyl) -3- [2,2,2-trifluoro-1-({[5- (4-methoxyphenyl) -2-thienyl] methyl} amino) ethyl] -1H-indole- 6-carbonitrile 1- (4-chlorobenzyl) -3- [2,2,2-trifluoro-1-({[5- (4-methoxyphenyl) -2-thienyl] methyl} amino) ethyl] -1H-indole -6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.81 (d, J = 8.3 Hz, 1H), 7.58-7.57 (m, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.41-7.37 (m , 2H), 7.31 (d, J = 8.7 Hz, 2H), 7.05-7.02 (m, 3H), 6.91 (d, J = 8.7 Hz, 2H), 6.76 (d, J = 3.4 Hz, 1H), 5.31 (s, 2H), 4.61 (q, J = 7.3 Hz, 1H), 4.05 (d, J = 14.5 Hz, 1H), 3.91 (d, J = 14.5 Hz, 1H), 3.84 (s, 3H), 2.05 (bs, 1H).

Example 19
1- (4-Chlorobenzyl) -3- {2,2,2-trifluoro-1-[(1,3-thiazol-2-ylmethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(1,3-thiazol-2-ylmethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.54 (d, J = 5.9 Hz, 1H), 7.80 (d, J = 8.5 Hz, 1H), 7.60-7.59 (m, 1H), 7.41-7.38 (m , 2H), 7.33 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 5.9 Hz, 1H), 7.04 (d, J = 8.3 Hz, 2H), 5.31 (s, 2H), 4.50 (q , J = 7.2 Hz 1H), 3.89 (d, J = 14.8 Hz, 1H), 3.79 (d, J = 14.8 Hz, 1H).
MS (ESI +) 461 (M ⁺ +1)

Example 20
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(pyridin-3-ylmethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl ) -3- {2,2,2-trifluoro-1-[(pyridin-3-ylmethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.53-8.47 (m, 2H), 7.81 (d, J = 8.0 Hz, 1H), 7.62-7.59 (m, 2H), 7.41-7.39 (m, 2H) , 7.33 (d, J = 8.4 Hz, 2H), 7.26-7.24 (m, 1H), 7.04 (d, J = 8.4 Hz, 2H), 5.31 (s, 2H), 4.50 (q, J = 7.4 Hz, 1H), 3.87 (d, J = 13.7 Hz, 1H), 3.79 (d, J = 13.7 Hz, 1H), 2.00 (bs, 1H).
MS (ESI +) 455 (M ⁺ +1)

Example 21
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(pyridin-2-ylmethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl ) -3- {2,2,2-trifluoro-1-[(pyridin-2-ylmethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.54-8.52 (m, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.64-7.59 (m, 1H), 7.57-7.56 (m, 1H) , 7.52 (s, 1H), 7.38-7.31 (m, 3H), 7.20-7.15 (2H, m),, 7.04 (d, J = 8.3 Hz, 2H), 5.31 (s, 2H), 4.57 (q, J = 7.2 Hz, 1H), 3.96 (d, J = 14.4 Hz, 1H), 3.90 (d, J = 14.4 Hz, 1H), 2.76 (bs, 1H).
MS (ESI +) 455 (M ⁺ +1)

Example 22
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(pyridin-4-ylmethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl ) -3- {2,2,2-trifluoro-1-[(pyridin-4-ylmethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.83 (d, J = 8.3 Hz, 1H), 7.71 (d, J = 3.2 Hz, 1H), 7.57-7.56 (m, 1H), 7.42-7.26 (m , 7H), 7.04 (d, J = 8.1 Hz, 2H), 5.31 (s, 2H), 4.68 (q, J = 7.2 Hz 1H), 4.18 (d, J = 15.4 Hz, 1H), 4.11 (d, J = 15.4 Hz, 1H), 2.52 (bs, 1H).
MS (ESI +) 455 (M ⁺ +1)

Example 23
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(2-thienylmethyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(2-thienylmethyl) amino] ethyl} -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.78 (d, J = 8.3 Hz, 1H), 7.58-7.57 (m, 1H), 7.40-7.37 (m, 2H), 7.33 (d, J = 8.3 Hz , 2H), 7.24 (dd, J = 5.1, 1.2 Hz, 1H), 7.04 (d, J = 8.3 Hz, 2H), 6.96-6.94 (m, 1H), 6.85-6.83 (m, 1H), 5.31 ( s, 2H), 4.57 (q, J = 7.2 Hz, 1H), 4.06 (d, J = 14.5 Hz, 1H), 3.95 (d, J = 14.5 Hz, 1H), 2.04 (bs, 1H).
MS (ESI +) 460 (M ⁺ +1)

Example 24
3- {1-[(1-Benzothien-2-ylmethyl) amino] -2,2,2-trifluoroethyl} -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile 3- {1 -[(1-benzothien-2-ylmethyl) amino] -2,2,2-trifluoroethyl} -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.81-7.79 (m, 2H), 7.68-7.66 (m, 1H), 7.59-7.58 (m, 1H), 7.40-7.26 (m, 6H), 7.05- 7.03 (m, 3H), 5.30 (s, 2H), 4.65-4.58 (m, 1H), 4.18-4.00 (m, 2H), 2.15 (bs, 1H).
MS (ESI +) 510 (M ⁺ +1)

Example 25
1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(3-phenoxybenzyl) amino] ethyl} -1H-indole-6-carbonitrile 1- (4-chlorobenzyl) -3- {2,2,2-trifluoro-1-[(3-phenoxybenzyl) amino] ethyl} -1H-indole-6-carbonitrile
MS (ESI +) 547 (M ⁺ +1)

Example 26
3- [1- (benzylamino) -2,2,2-trifluoroethyl] -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile 3- [1- (benzylamino) -2,2 , 2-trifluoroethyl] -1- (4-chlorobenzyl) -1H-indole-6-carbonitrile
MS (ESI +) 454 (M ⁺ +1)

  Similar to the compound of Example 4, the compounds of Examples 27 to 49 having the structural formulas shown in Tables 3 to 5 were produced.

Example 27
N- {1- [6-Cyano-1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} furan-2-sulfonamide N- {1- [ 6-cyano-1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} furan-2-sulfonamide
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.69 (d, J = 8.3 Hz, 1H), 7.62 (s, 1H), 7.40 (dd, J = 8.3, 1.3 Hz, 1H), 7.36 (s, 1H ), 7.26-7.23 (m, 2H), 7.16 (d, J = 7.6 Hz, 1H), 6.96-6.95 (m, 2H), 6.88 (d, 1H, J = 7.6 Hz), 6.32-6.31 (m, 1H), 5.32-5.26 (m, 2H), 5.26 (s, 2H), 2.34 (s, 3H).
MS (ESI +) 474 (M ⁺ +1)

Example 28
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -2-methoxybenzenesulfonamide N- {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -2-methoxybenzenesulfonamide
MS (ESI +) 534 (M ⁺ +1)

Example 29
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -3-methoxybenzenesulfonamide N- {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -3-methoxybenzenesulfonamide
¹ H-NMR (400 MHz, DSMO-d ₆ ) δ 9.07 (d, J = 8.5 Hz, 1H), 8.03 (s, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.75 (s, 1H ), 7.41 (d, J = 8.5 Hz, 2H), 7.30 (dd, J = 8.4, 1.3 Hz, 1H), 7.16-7.09 (m, 3H), 7.06-7.01 (m, 2H), 6.85-6.82 ( m, 1H), 5.56-5.49 (m, 1H), 5.40 (d, J = 16.0 Hz, 1H), 5.36 (d, J = 16.0 Hz, 1H), 3.50 (s, 3H).
MS (ESI +) 534 (M ⁺ +1)

Example 30
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -2-nitrobenzenesulfonamide N- {1- [ 1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -2-nitrobenzenesulfonamide
¹ H-NMR (400 MHz, CDCl ₃ ) δ 8.04-8.02 (m, 1H), 7.80-7.78 (m, 1H), 7.73 (d, J = 8.3 Hz, 1H), 7.66-7.54 (m, 3H) , 7.40-7.38 (m, 2H), 7.33 (d, J = 8.3 Hz, 2H), 7.01 (d, J = 8.3 Hz, 2H), 6.19 (d, J = 9.5 Hz, 1H), 5.57-5.50 ( m, 1H), 5.26 (s, 2H).
MS (ESI +) 549 (M ⁺ +1)

Example 31
N- [1- (1-benzyl-6-cyano-1H-indol-3-yl) -2,2,2-trifluoroethyl] methanesulfonamide N- [1- (1-benzyl-6-cyano- 1H-indol-3-yl) -2,2,2-trifluoroethyl] methanesulfonamide
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.86 (d, J = 8.3 Hz, 1H), 7.63 (d, J = 1.4 Hz, 1H), 7.46-7.42 (m, 2H), 7.40-7.33 (m , 3H), 7.14-7.09 (m, 2H), 5.55-5.44 (m, 1H), 5.36 (d, J = 15.8 Hz, 1H), 5.32 (d, J = 15.8 Hz, 1H), 4.92-4.86 ( m, 1H), 3.05 (s, 3H).
MS (ESI +) 408 (M ⁺ +1)

Example 32
N- [1- (1-Benzyl-6-cyano-1H-indol-3-yl) -2,2,2-trifluoroethyl] -2,4,6-trimethylbenzenesulfonamide N- [1- ( 1-benzyl-6-cyano-1H-indol-3-yl) -2,2,2-trifluoroethyl] -2,4,6-trimethylbenzenesulfonamide
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.66 (d, J = 8.3 Hz, 1H), 7.56 (s, 1H), 7.40-7.31 (m, 5H), 7.14-7.07 (m, 2H), 6.81 (s, 2H), 5.37-5.14 (m, 2H), 5.26 (s, 2H), 2.53 (s, 6H), 2.24 (s, 3H).
MS (ESI +) 512 (M ⁺ +1)

Example 33
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} benzenesulfonamide N- {1- [1- ( 4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} benzenesulfonamide
MS (ESI +) 504 (M ⁺ +1)

Example 34
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} benzamide N- {1- [1- (4- chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} benzamide
MS (ESI +) 468 (M ⁺ +1)

Example 35
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} morpholine-4-carboxamide N- {1- [1 -(4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} morpholine-4-carboxamide
MS (ESI +) 477 (M ⁺ +1)

Example 36
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -1-phenylmethanesulfonamide N- {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -1-phenylmethanesulfonamide
MS (ESI +) 518 (M ⁺ +1)

Example 37
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} methanesulfonamide N- {1- [1- ( 4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} methanesulfonamide
MS (ESI +) 442 (M ⁺ +1)

Example 38
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -2-phenoxyacetamide N- {1- [1 -(4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -2-phenoxyacetamide
MS (ESI +) 498 (M ⁺ +1)

Example 39
(E) -N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -2-phenylethanesulfonamide ( E) -N- {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -2-phenylethenesulfonamide
MS (ESI +) 530 (M ⁺ +1)

Example 40
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -4-phenoxybenzenesulfonamide N- {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -4-phenoxybenzenesulfonamide
MS (ESI +) 597 (M ⁺ +1)

Example 41
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -3-phenoxybenzenesulfonamide N- {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -3-phenoxybenzenesulfonamide
MS (ESI +) 597 (M ⁺ +1)

Example 42
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} biphenyl-4-sulfonamide N- {1- [ 1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} biphenyl-4-sulfonamide
MS (ESI +) 581 (M ⁺ +1)

Example 43
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} biphenyl-3-sulfonamide N- {1- [ 1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} biphenyl-3-sulfonamide
MS (ESI +) 581 (M ⁺ +1)

Example 44
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} thiophene-2-sulfonamide N- {1- [ 1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} thiophene-2-sulfonamide
MS (ESI +) 510 (M ⁺ +1)

Example 45
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} thiophene-3-sulfonamide N- {1- [ 1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} thiophene-3-sulfonamide
MS (ESI +) 510 (M ⁺ +1)

Example 46
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -1-benzothiophene-2-sulfonamide N- {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -1-benzothiophene-2-sulfonamide
MS (ESI +) 561 (M ⁺ +1)

Example 47
Benzyl 4-[({1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} amino) sulfonyl] piperidine-1-carboxy Rate benzyl 4-[({1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} amino) sulfonyl] piperidine-1-carboxylate
MS (ESI +) 646 (M ⁺ +1)

Example 48
N- {1- [6-cyano-1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} methanesulfonamide N- {1- [6-cyano -1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} methanesulfonamide
MS (ESI +) 422 (M ⁺ +1)

Example 49
N- {1- [6-cyano-1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} benzenesulfonamide N- {1- [6-cyano -1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} benzenesulfonamide
MS (ESI +) 484 (M ⁺ +1)

  Similar to the compound of Example 1, the compounds of Examples 50 to 51 whose structural formulas are shown in Table 6 were produced.

Example 50
tert-butyl [1- (1-benzyl-6-cyano-1H-indol-3-yl) -2,2,2-trifluoroethyl] carbamate tert-butyl [1- (1-benzyl-6-cyano- 1H-indol-3-yl) -2,2,2-trifluoroethyl] carbamate
¹ H-NMR (400 MHz, CDCl ₃ ) δ 7.72 (d, J = 8.3 Hz, 1H), 7.62 (s, 1H), 7.43-7.30 (m, 5H), 7.14-7.09 (m, 2H), 5.58 -5.63 (m, 1H), 5.34 (s, 2H), 5.10-4.95 (m, 1H), 1.47 (s, 9H).
MS (ESI +) 430 (M ⁺ +1)

Example 51
tert-butyl {1- [6-cyano-1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} carbamate tert-butyl {1- [6-cyano -1- (3-methylbenzyl) -1H-indol-3-yl] -2,2,2-trifluoroethyl} carbamate
MS (ESI +) 444 (M ⁺ +1)

  In the same manner as the compound of Example 2, the compounds of Examples 52 to 53 whose structural formulas are shown in Table 7 were produced.

Example 52
3- (1-Amino-2,2,2-trifluoroethyl) -1- (3-methylbenzyl) -1H-indole-6-carbonitrile 3- (1-amino-2,2,2-trifluoroethyl) -1- (3-methylbenzyl) -1H-indole-6-carbonitrile
MS (ESI +) 344 (M ⁺ +1)

Example 53
N-benzyl-N '-{1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} sulfamide N-benzyl-N' -{1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} sulfamide
¹ H-NMR (400 MHz, DSMO-d ₆ ) δ 8.57 (d, J = 9.3 Hz, 1H), 8.22 (s, 1H), 8.03 (s, 1H), 7.95 (d, J = 8.3 Hz, 1H ), 7.54-7.51 (m, 1H), 7.46-7.43 (m, 1H), 7.32 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 8.3 Hz, 2H), 7.17-7.12 (m, 3H), 6.94-6.92 (m, 2H), 5.55-5.50 (m, 2H), 5.38-5.34 (m, 1H), 3.83-3.78 (m, 1H), 3.60-3.54 (m, 1H).
MS (ESI +) 533 (M ⁺ +1)

  In the same manner as the compound of Example 8, the compounds of Examples 54 to 55 whose structural formulas are shown in Table 8 were produced.

Example 54
N- {1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} morpholine-4-sulfonamide N- {1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} morpholine-4-sulfonamide
MS (ESI +) 513 (M ⁺ +1)

Example 55
N '-{1- [1- (4-Chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -N, N-diethylsulfamide N' -{1- [1- (4-chlorobenzyl) -6-cyano-1H-indol-3-yl] -2,2,2-trifluoroethyl} -N, N-diethylsulfamide
¹ H-NMR (400 MHz, DSMO-d ₆ ) δ 8.54 (bs, 1H), 8.27-8.26 (m, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.44-7.40 (m, 3H) , 7.29 (d, J = 8.4 Hz, 2H), 5.56 (d, J = 15.5 Hz, 1H), 5.49 (d, J = 15.5 Hz, 1H), 5.38-5.30 (m, 1H), 2.78 (q, J = 7.1 Hz, 4H), 0.75 (t, J = 7.1 Hz, 6H).
MS (ESI +) 499 (M ⁺ +1)

Test example 1
Binding inhibition test Insect cells infected with baculovirus to express human GRα protein were treated with approximately equal volume of binding buffer (10 mM Tris-Cl, 1.5 mM EDTA, 10% glycerol, 5 mM DTT, 20 mM sodium molybdate). , pH 7.6). The operation of rapidly freezing with liquid nitrogen and thawing at room temperature was performed twice to disrupt the cell membrane. Centrifugation was performed at 4 ° C. and 100,000 g for 1 hour in an ultracentrifuge, and the obtained supernatant was used as a cytoplasmic fraction containing human GRα protein.
A 96-well polypropylene plate (Coaster, etc.) was placed on ice, and 1 μL of DMSO or a test compound was placed in each well. Add 50 μL each of ³ H-Dex (tritiated dexamethasone; Amersham) / GR protein solution (diluted with binding buffer) diluted to 10 nM with binding buffer, and stir gently with a plate mixer And then allowed to stand at 4 ° C. for 16-20 hours (DMSO final concentration: 1%).
50 μL of dextran-coated activated carbon (Sigma) 5% solution suspended in a binding buffer was placed in each well and gently stirred for 30 seconds with a plate mixer. Thereafter, 4 ° C., centrifuged for 5 minutes at 2500 rotation was measured ³ H count of the supernatant 50μL in TopCount (PerkinElmer). Each test compound was measured twice.
The binding activity was calculated as follows. The average value of ³ H count in the presence of 10 μM dexamethasone (Dex) was defined as NSB (non-specific binding), and the binding inhibition rate of each well was calculated by the following formula. Binding inhibition rate (%) = 100 × {1- (each well cpm value−NSB) / (DMSO well cpm value average−NSB)} (cpm is an abbreviation of count per minute) The average binding inhibition rate for each well was calculated and used as the binding inhibition rate for each test compound.
Test example 2
TAT (tyrosine aminotransferase) assay H4-III-E maintained in passage in α-MEM medium A (10% non-immobilized FBS, 50 μM 2-mercapto-ethanol) α-MEM medium A or α-MEM medium The suspension was suspended in B (phenol red-free, 10% non-immobilized FBS, 50 μM 2-mercapto-ethanol added), seeded in a 96-well plate at 2 × 10 ⁴ cells / 100 μL / well, and cultured overnight. The medium supernatant was removed, and 100 μL of the test compound (diluted with α-MEM medium A or α-MEM medium B) was added, followed by further overnight culture. When measuring agonist activity, add test compound alone, and when measuring antagonist activity, add dexamethasone at the same time 0.005 μM to determine how much the test compound suppresses TAT activity induction by dexamethasone. investigated.
The culture supernatant of the plate is removed by aspiration, and cell lysate (1% NP-40, 0.2% TritonX-100, 0.25% DOC, 0.1% SDS, 1 mM EGTA, 150 mM NaCl, Tris (pH 7.4), Protease inhibitor cocktail After adding 20 μL of [2.5 mg / ml aprotinin, 2.5 mg / ml leupeptin, 2.5 mg / ml soybean trypsin inhibitor]), TAT reaction reagent (10N KOH, 0.125M KH ₂ PO ₄ , 0.5M α-ketoglutarate, 5mM Pyridoxal- 150 μL of 5′phosphate, L-tyrosine) was added and reacted at 37 ° C. for 15 minutes. Furthermore, 20 μL of 10N KOH was added, reacted at 37 ° C. for 30 minutes, and absorbance at 331 nm was measured with a microplate reader (SPECTRA MAX250).
The value obtained by subtracting the average value of the absorbance of the non-drug-added group to which the drug and TAT reaction solution were not added from the average value of the absorbance of the well to which the test compound was added was compared with the Dex-treated group (0.5 nM to 5 μM) The agonist activity (%) was calculated based on the following calculation formula, assuming that the absorbance of the group exhibiting the maximum activity in the common ratio 10) was 100%. Agonist activity (%) = 100 × [(absorbance of the drug-treated group) − (absorbance of the TAT reaction reagent non-added group)] / [(absorbance of the Dex-treated group showing the maximum value) − (TAT reaction reagent non-added group) Absorbance of
On the other hand, antagonist activity was calculated as follows. Antagonist activity (%) = Inhibition rate of TAT activity increase by Dex (%) = 100−100 × [(absorbance of drug-treated group) − (absorbance of non-drug group)] / [(absorbance of Dex-treated group) − (Absorbance of the group without added drug)]
Tables 9 and 10 show the results of the binding inhibition test of Test Example 1. From the results of Table 9 and Table 10, it can be seen that the compound of the present invention has an action as a GR function regulator.

  The condensed pyrrole derivatives and their pharmaceutically acceptable salts according to the present invention can be used as non-steroidal anti-inflammatory drugs or anti-diabetic drugs with reduced side effects compared to steroidal anti-inflammatory drugs.

Claims (11)

Formula (1):

[Wherein, R ¹ represents a substituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, substituted or unsubstituted Substituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted alkanoyl group, substituted or unsubstituted Substituted alkoxycarbonyl group, substituted or unsubstituted alkylsulfonyl group, substituted or unsubstituted cycloalkyloxy group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted cycloalkyloxycarbonyl group, substituted or unsubstituted Cycloalkylsulfo Group, substituted or unsubstituted aryloxy group, substituted or unsubstituted aroyl group, substituted or unsubstituted aryloxycarbonyl group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroaryloxy group, substituted Or an unsubstituted heteroarylcarbonyl group, a substituted or unsubstituted heteroaryloxycarbonyl group, a substituted or unsubstituted heteroarylsulfonyl group, a substituted or unsubstituted aralkyloxy group, a substituted or unsubstituted aralkylcarbonyl group, substituted or Unsubstituted aralkyloxycarbonyl group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkyloxy group, substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted heteroarral Killoxycarbonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic carbonyl group, substituted or Represents an unsubstituted saturated or unsaturated aliphatic heterocyclic sulfonyl group, a substituted or unsubstituted carbamoyl group, or a substituted or unsubstituted sulfamoyl group;
R ² represents a hydrogen atom, a halogen atom, a carboxyl group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, substituted or unsubstituted Substituted aralkyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted alkanoyl group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted saturated or unsaturated An aliphatic heterocyclic group, or a carbamoyl group that may be substituted with a substituted or unsubstituted alkyl group,
^{-W 4 = W 5 -W 6 =} W 7 - has the following formula (a) ~ (h):
^{(A) -CR 4 = CR 5} -CR 6 = CR 7 -;
^{(B) -N = CR 5 -CR} 6 = CR 7 -;
^{(C) -CR 4 = N-} CR 6 = CR 7 -;
^{(D) -CR 4 = CR 5} -N = CR 7 -;
^{(E) -CR 4 = CR 5} -CR 6 = N-;
^{(F) -N = CR 5 -N} = CR 7 -;
^{(G) -CR 4 = N-} CR 6 = N-;
^{(H) -CR 4 = N-} N = CR 7 -
[Wherein, R ⁴ , R ⁵ , R ⁶ and R ⁷ are each independently the same or different and represent the formula: -EA, wherein E is a single bond or the following formula 1 )~14):
1) -C (R ¹⁶ ) R ^17- ,
2) -O-,
3) -S (= O) m-,
4) -S (= O) ₂ NR ^16- ,
5) -C (= O)-,
6) -C (= O) O-,
7) -C (= O) NR ^16- ,
8) −C (= NR ¹⁶ ) NR ¹⁷ −,
9) -NR ^16- ,
^{10) -N (R 16) C} (= O) -,
11) -N (R ¹⁶ ) S (= O) _2- ,
^{12) -N (R 16) C} (= O) N (R 17) -,
^{13) -N (R 16) S} (= O) 2 N (R 17) -,
14) -P (= O) (OR ¹⁶ ) _2-
(Wherein R ¹⁶ and R ¹⁷ each independently represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an alkoxy group having 1 to 3 carbon atoms, or formula 8). In 12) and 13), R ¹⁶ and R ¹⁷ may be bonded to each other to represent an alkylene group having 2 to 4 carbon atoms, and m represents 0, 1 or 2. ) Represents a group selected from
When E is a single bond, A is a hydrogen atom, halogen atom, cyano group, nitro group, hydroxyl group, carboxyl group, substituted or unsubstituted alkyl group, substituted or unsubstituted alkenyl group, substituted or unsubstituted alkynyl. Group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted cycloalkenyl group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aralkyl group, substituted or unsubstituted Represents a heteroaralkyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group,
When E represents a group selected from the above formulas 1) to 14), A represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, substituted or An unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, Or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group. ]
Represents a group selected from
R ⁸ represents a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or an alkyl group having 1 to 3 carbon atoms substituted with one or more halogen atoms,
R ⁹ represents an alkyl group substituted with one or more halogen atoms, or a cycloalkyl group substituted with one or more halogen atoms;
R ¹⁰ represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, substituted Or an unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, a substituted or unsubstituted alkanoyl group, a substituted or unsubstituted alkoxycarbonyl group, Substituted or unsubstituted alkylsulfinyl group, substituted or unsubstituted alkylsulfonyl group, substituted or unsubstituted alkenylcarbonyl group, substituted or unsubstituted alkenyloxycarbonyl group, substituted or unsubstituted alkenylsulfinyl group, substituted or unsubstituted of Lucenylsulfonyl group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted cycloalkyloxycarbonyl group, substituted or unsubstituted cycloalkylsulfinyl group, substituted or unsubstituted cycloalkylsulfonyl group, substituted or unsubstituted Aroyl group, substituted or unsubstituted aryloxycarbonyl group, substituted or unsubstituted arylsulfinyl group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylcarbonyl group, substituted or unsubstituted heteroaryloxy Carbonyl group, substituted or unsubstituted heteroarylsulfinyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted aralkylcarbonyl group, substituted or unsubstituted aralkylo Sicarbonyl group, substituted or unsubstituted aralkylsulfinyl group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted heteroaralkyloxycarbonyl group, substituted or unsubstituted heteroaralkyl Sulfinyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, substituted or unsubstituted thiocarbamoyl group, substituted or unsubstituted saturated or unsaturated aliphatic Heterocyclic group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic carbonyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic sulfinyl group, or substituted or unsubstituted saturated or unsaturated Represents an aliphatic heterocyclic sulfonyl group. ]
Or a prodrug thereof, or a pharmaceutically acceptable salt thereof. R ⁸ represents a hydrogen atom, R ¹⁰ represents a hydrogen atom, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted Or an unsubstituted cycloalkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, a substituted or unsubstituted alkanoyl group, Substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted alkylsulfonyl group, substituted or unsubstituted alkenylcarbonyl group, substituted or unsubstituted alkenyloxycarbonyl group, substituted or unsubstituted alkenylsulfonyl group, substituted or unsubstituted The cycloalkyl carboni A group, a substituted or unsubstituted cycloalkyloxycarbonyl group, a substituted or unsubstituted cycloalkylsulfonyl group, a substituted or unsubstituted aroyl group, a substituted or unsubstituted aryloxycarbonyl group, a substituted or unsubstituted arylsulfonyl group, A substituted or unsubstituted heteroarylcarbonyl group, a substituted or unsubstituted heteroaryloxycarbonyl group, a substituted or unsubstituted heteroarylsulfonyl group, a substituted or unsubstituted aralkylcarbonyl group, a substituted or unsubstituted aralkyloxycarbonyl group, Substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted heteroaralkyloxycarbonyl group, substituted or unsubstituted heteroaralkylsulfonyl group Group, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, substituted or unsubstituted thiocarbamoyl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted saturated Or an unsaturated aliphatic heterocyclic carbonyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic sulfonyl group,
Or R ⁸ represents an alkyl group having 1 to 3 carbon atoms, or an alkyl group having 1 to 3 carbon atoms substituted with one or more halogen atoms, and R ¹⁰ represents a substituted alkyl group or substituted Or an unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkenyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, Substituted or unsubstituted aralkyl group, substituted or unsubstituted heteroaralkyl group, substituted or unsubstituted alkanoyl group, substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted alkylsulfonyl group, substituted or unsubstituted alkenylcarbonyl Group, substituted or unsubstituted alkenyloxycarbonyl group, substituted or Substituted alkenylsulfonyl group, substituted or unsubstituted cycloalkylcarbonyl group, substituted or unsubstituted cycloalkyloxycarbonyl group, substituted or unsubstituted cycloalkylsulfonyl group, substituted or unsubstituted aroyl group, substituted or unsubstituted Aryloxycarbonyl group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylcarbonyl group, substituted or unsubstituted heteroaryloxycarbonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted Aralkylcarbonyl group, substituted or unsubstituted aralkyloxycarbonyl group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylcarbonyl group, substituted or unsubstituted hetero Aralkyloxycarbonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted carbamoyl group, substituted or unsubstituted sulfamoyl group, substituted or unsubstituted thiocarbamoyl group, substituted or unsubstituted saturated or unsaturated Represents an aliphatic heterocyclic group, a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic carbonyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic sulfonyl group, and the substitution of the substituted alkyl group The group is substituted or unsubstituted amino group, substituted or unsubstituted aryloxy group, substituted or unsubstituted heteroaryloxy group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic oxy group, substituted or unsubstituted Substituted arylthio groups, substituted or unsubstituted hete Arylthio group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic thio group, substituted or unsubstituted arylsulfonyl group, substituted or unsubstituted heteroarylsulfonyl group, substituted or unsubstituted saturated or unsaturated fat Heterocyclic sulfonyl group, substituted or unsubstituted aralkyloxy group, substituted or unsubstituted heteroaralkyloxy group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted carbamoyl The compound or prodrug thereof according to claim 1, which is a group, a substituted or unsubstituted sulfamoyl group, a substituted or unsubstituted thiocarbamoyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group Or their pharmacological Salt content. ^{-W 4 = W 5 -W 6 =} W 7 - is of the formula ^{(a): - CR 4 =} CR 5 -CR 6 = CR 7 - ( ^{wherein, R 4, R 5, R} 6 and R ⁷ wherein The compound according to claim 1 or 2 or a prodrug thereof, or a pharmaceutically acceptable salt thereof, which represents the same as defined in item 1. ^{-W 4 = W 5 -W 6 =} W 7 - is of formula ^{(d): - CR 4 =} CR 5 -N = CR 7 - ( wherein, R ^4, R ⁵ and R ⁷ claim 1 as defined Or a prodrug thereof, or a pharmaceutically acceptable salt thereof. R ¹ represents a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted cycloalkyl group, substituted or unsubstituted The compound according to any one of claims 1 to 4, which represents an alkyl group substituted with a substituted cycloalkyl group or an alkyl group substituted with a substituted or unsubstituted saturated or unsaturated aliphatic heterocycle. Or a prodrug thereof, or a pharmaceutically acceptable salt thereof. R ² represents a hydrogen atom or a substituted or unsubstituted alkyl group having 1 to 6 carbon atoms, the compound according to any one of claims 1 to 5 or a prodrug thereof, or a pharmaceutically acceptable salt thereof. salt. The compound according to any one of claims 1 to 6 or a prodrug thereof, wherein R ⁹ represents an alkyl group having 1 to 6 carbon atoms substituted with 1 to 7 fluorine atoms or chlorine atoms. Or a pharmaceutically acceptable salt thereof. The compound according to claim 7 or a prodrug thereof, or a pharmaceutically acceptable salt thereof, wherein R ⁹ represents a trifluoromethyl group. R ¹⁰ is a substituted or unsubstituted aralkyl group, a substituted or unsubstituted heteroaralkyl group, a substituted or unsubstituted, saturated or alkyl group substituted by an aliphatic heterocyclic group of unsaturated, substituted or unsubstituted aryl group Substituted or unsubstituted heteroaryl group, substituted or unsubstituted saturated or unsaturated aliphatic heterocyclic group, substituted or unsubstituted aralkylsulfonyl group, substituted or unsubstituted heteroaralkylsulfonyl group, substituted or unsubstituted An alkylsulfonyl group substituted with a saturated or unsaturated aliphatic heterocyclic group, a substituted or unsubstituted arylsulfonyl group, a substituted or unsubstituted heteroarylsulfonyl group, or a substituted or unsubstituted saturated or unsaturated aliphatic group Any one of claims 1 to 8, which represents a heterocyclic sulfonyl group. Compound or a prodrug thereof or a pharmaceutically acceptable salt thereof, as claimed in claim.   A glucocorticoid receptor function regulator comprising the compound according to any one of claims 1 to 9, or a prodrug thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.   A therapeutic or prophylactic agent for inflammatory diseases or diabetes comprising the compound according to any one of claims 1 to 9, or a prodrug thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.