JP7068743B2 - A pharmaceutical composition containing a condensed ring derivative having MGAT2 inhibitory activity. - Google Patents

Description

The present invention relates to a compound having a monoacylglycerol acyltransferase 2 (hereinafter also referred to as MGAT2) inhibitory action, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing the same.

Obesity is defined as the accumulation of excess fat or adipose tissue in the body relative to lean body mass and is recognized as a major risk factor for health problems. Body mass index (BMI) is a simple index of height-to-weight ratio commonly used to classify an adult (15 years or older) population or individual as overweight or obese. It is defined as body weight (kg / m ² ) in kilograms divided by the square of height in meters. According to the World Health Organization, a BMI of 25 kg / m ² or more is "overweight" and a BMI of 30 kg / m ² or more is "obesity". On the other hand, the Japan Society for the Study of Obesity defines a BMI of 25 kg / m ² or more as "obesity". This is because the number of obesity-related diseases, including diabetes and dyslipidemia, increases with BMI, and the average BMI for the number of diseases is 1.0 or greater at 25 kg / m ² . According to a 2005 survey by the World Health Organization, about 1.6 billion people are overweight and at least 400 million are obese worldwide. Obesity is mainly caused by an increase in the ratio of caloric intake to physical activity and consumption in daily life. The number of obese people is increasing due to the increase in intake of high-fat and high-sugar foods in recent years, and it is expected that more than 700 million people will be diagnosed with obesity worldwide in 2015. These treatments include diet, exercise, and drug therapy. Drugs such as orlistat, mazindol, and sibutramine are used in drug therapy, but none are satisfactory in terms of both efficacy and side effects.
Excessive intake of triglycerides is a cause of obesity. Triglycerides ingested by the diet are decomposed into 2-monoacylglycerol and free fatty acids by pancreatic lipase in the gastrointestinal tract and absorbed by small intestinal epithelial cells. The acyl group of a free fatty acid is transferred to 2-monoacylglycerol by a monoacylglycerol acyltransferase (MGAT). The diacylglycerol produced is further converted to triglycerides by the diacylglycerol acyltransferase (DGAT).
Three isoforms of MGAT have been identified: MGAT1, MGAT2, and MGAT3. Of these, MGAT2 and MGAT3 are highly expressed in the small intestine and are considered to be involved in fat absorption in the small intestine.
Experiments with MGAT2 knockout mice have reported that the expression of MGAT2 in the small intestine was enhanced and the MGAT activity was increased by a high-fat diet load (Non-Patent Document 1). Furthermore, in MGAT2 knockout mice, suppression of weight gain due to high-fat diet load, suppression of insulin resistance induction, suppression of blood cholesterol elevation, suppression of fatty liver formation, etc., and enhancement of energy consumption have been confirmed (non-patent). Document 2).
So far, compounds having MGAT2 inhibitory activity have been reported (Patent Documents 1 to 19 and Non-Patent Documents 3 to 13), but the compounds of the present invention shown below are not disclosed.

International Publication No. 2010/095767 International Publication No. 2012/091010 International Publication No. 2012/124744 International Publication No. 2013/08234 International Publication No. 2013/112323 International Publication No. 2013/11006 International Publication No. 2013/116075 International Publication No. 2014/074365 International Publication No. 2014/133134 International Publication No. 2014/193884 Japanese Unexamined Patent Publication No. 2014-5245 Japanese Unexamined Patent Publication No. 2014-9165 International Publication No. 2015/11246 International Publication No. 2015/129845 International Publication No. 2015/134699 International Publication No. 2015/134701 International Publication No. 2015/191681 International Publication No. 2016/121782 International Publication No. 2017/06924

Journal of Biological Chemistry (2004), 279, 18878-18886 Nature Medicine (2009), 15, (4), 442-446 Bioorganic & Medicinal Chemistry Letter (2013), 23, 2721-2726 Med. Chem. Commun (2013), 4, 1305-1311 Bioorganic & Medicinal Chemistry Letter (2015), 23, 5922-5931 Bioorganic & Medicinal Chemistry Letter (2015), 23, 4544-4560 Journal of Lipid Research 2015, 56, 747-753 European Journal of Pharmacology, 2015, 758, 72-81 Journal of Medicinal Chemistry (2015), 58, 3892-3909 HETEROCYCLES 2016, 92, 470-484 Chemical and Pharmaceutical Bulletin, 2016, 64, 228-238 European Journal of Pharmacology, 2016, 791, 569-577 Analytical Biochemistry, 2016, 501, 48-55

An object of the present invention is to provide a compound having an MGAT2 inhibitory action, a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing them.

As a result of diligent research, the present inventors have found a pharmaceutical composition containing an excellent compound having an MGAT2 inhibitory action. That is, the present invention relates to the following.

（式中、
式：

で示される部分が

であり；
Ｘは、Ｃ（＝Ｏ）、Ｃ（＝Ｓ）、またはＳＯ₂であり；
ｍは、０または１であり；

Ｒ¹は、水素、ヒドロキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルであり、ただしＲ¹は、式：

でなく；

Ｒ^2aは、式：

（式中、環Ｃは、芳香族炭素環、芳香族複素環、非芳香族炭素環、または非芳香族複素環であり；
Ｒ⁵は、それぞれ独立して、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
ｎは、１～５の整数である）であり、
Ｒ^2bは、シアノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキニル、または置換もしくは非置換のアルキルスルホニルであり、または
Ｒ^2aおよびＲ^2bは、隣接する炭素原子と一緒になって、環Ｂを形成してもよく、
環Ｂは、置換もしくは非置換の非芳香族炭素環または置換もしくは非置換の非芳香族複素環であり；

Ｒ^3aは、水素、ハロゲン、ヒドロキシ、シアノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環式基オキシ、置換もしくは非置換の非芳香族炭素環式基オキシ、置換もしくは非置換の芳香族複素環式基オキシ、置換もしくは非置換の非芳香族複素環式基オキシ、置換もしくは非置換の芳香族炭素環式基スルホニル、置換もしくは非置換の非芳香族炭素環式基スルホニル、置換もしくは非置換の芳香族複素環式基スルホニル、または置換もしくは非置換の非芳香族複素環式基スルホニルであり、
Ｒ^3bは、水素、ハロゲン、ヒドロキシ、シアノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環式基オキシ、置換もしくは非置換の非芳香族炭素環式基オキシ、置換もしくは非置換の芳香族複素環式基オキシ、置換もしくは非置換の非芳香族複素環式基オキシ、置換もしくは非置換の芳香族炭素環式基スルホニル、置換もしくは非置換の非芳香族炭素環式基スルホニル、置換もしくは非置換の芳香族複素環式基スルホニル、または置換もしくは非置換の非芳香族複素環式基スルホニルであり、
Ｒ^3aとＲ^3bは、隣接する炭素原子と一緒になって、置換もしくは非置換の非芳香族炭素環または置換もしくは非置換の非芳香族複素環を形成してもよく、または
Ｒ^2bとＲ^3bは、隣接する炭素原子と一緒になって、置換もしくは非置換の非芳香族炭素環または置換もしくは非置換の非芳香族複素環を形成してもよく；

Ｒ^4aは、式：

であり；
Ｌ¹は、単結合または置換もしくは非置換のアルキレンであり、
Ｌ²は、単結合、－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｏ－、－Ｏ－Ｃ（＝Ｏ）－、－Ｎ（Ｈ）－、－Ｃ（＝Ｏ）－Ｎ（Ｈ）－、－Ｎ（Ｈ）－Ｃ（＝Ｏ）－、－Ｎ（Ｈ）－Ｃ（＝Ｏ）－Ｎ（Ｈ）－、－Ｃ（＝Ｏ）－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－、－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－、－Ｓ（＝Ｏ）₂－Ｎ（Ｈ）－、－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－Ｎ（Ｈ）－、または－Ｓ（＝Ｏ）₂－Ｎ（Ｈ）－Ｃ（＝Ｏ）－であり、
Ｌ³は、単結合または置換もしくは非置換のアルキレンであり、
Ｒ⁷は、水素、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
ただし、Ｌ¹、Ｌ²、およびＬ³が単結合の場合は、Ｒ⁷は、水素、またはハロゲンではなく、
Ｒ^4bは、ハロゲン、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｒ^4c’は、水素、ハロゲン、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｌは、それぞれ独立して、単結合、アルキレン、またはＣ（＝Ｏ）であり、
Ｒ^S1およびＲ^S2は、それぞれ独立して、水素、置換もしくは非置換のアルキル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、または置換もしくは非置換の非芳香族複素環式基であり、または、
同一の硫黄原子に結合しているＲ^S1およびＲ^S2は当該硫黄原子と一緒になって置換もしくは非置換の非芳香族複素環を形成してもよく；
Ｒ^Nは、それぞれ独立して、水素、シアノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、または置換もしくは非置換の非芳香族複素環カルボニルである）で示される化合物、（ただし、以下の化合物を除く

）またはその製薬上許容される塩、を含有する医薬組成物。
［２］環Ｂが、以下のいずれかの式で示される、前記［１］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
式：

（式中、
Ｂ¹は、ＣＲ^11aＲ^11b、ＮＲ^11c、Ｏ、またはＳであり、
Ｂ²は、ＣＲ^12aＲ^12b、ＮＲ^12c、Ｏ、またはＳであり、
Ｂ³は、ＣＲ^13aＲ^13b、ＮＲ^13c、Ｏ、またはＳであり、
Ｂ⁴は、ＣＲ^14aＲ^14b、ＮＲ^14c、Ｏ、またはＳであり、および
Ｂ⁵は、ＣＲ^15aＲ^15b、ＮＲ^15c、Ｏ、またはＳであり、
Ｒ^11a、Ｒ^12a、Ｒ^13a、Ｒ^14a、およびＲ^15aは、それぞれ独立して、水素、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｒ^11b、Ｒ^12b、Ｒ^13b、Ｒ^14b、およびＲ^15bは、それぞれ独立して、水素、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｒ^11c、Ｒ^12c、Ｒ^13c、Ｒ^14c、およびＲ^15cは、それぞれ独立して、水素、シアノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルであり、
または、Ｒ^11aとＲ^12a、Ｒ^12aとＲ^13a、Ｒ^13aとＲ^14a、および／またはＲ^14aとＲ^15aは、隣接する炭素原子と一緒になって、置換もしくは非置換の芳香族炭素環、置換もしくは非置換の非芳香族炭素環、置換もしくは非置換の芳香族複素環、または置換もしくは非置換の非芳香族複素環を形成してもよく、
および／または、Ｒ^11cとＲ^12a、Ｒ^11cとＲ^12c、Ｒ^12cとＲ^11a、Ｒ^12cとＲ^13a、Ｒ^12cとＲ^13c、Ｒ^13cとＲ^12a、Ｒ^13cとＲ^14a、Ｒ^13cとＲ^14c、Ｒ^14cとＲ^13a、Ｒ^14cとＲ^15a、Ｒ^14cとＲ^15c、および／またはＲ^15cとＲ^14aは、隣接する原子と一緒になって、置換もしくは非置換の芳香族複素環または置換もしくは非置換の非芳香族複素環を形成してもよく、
および／または、Ｒ^11aとＲ^13a、Ｒ^11aとＲ^13c、Ｒ^11aとＲ^14a、Ｒ^11aとＲ^14c、Ｒ^11aとＲ^15a、Ｒ^11aとＲ^15c、Ｒ^11cとＲ^13a、Ｒ^11cとＲ^13c、Ｒ^11cとＲ^14a、Ｒ^11cとＲ^14c、Ｒ^11cとＲ^15a、Ｒ^11cとＲ^15c、Ｒ^12aとＲ^14a、Ｒ^12aとＲ^14c、Ｒ^12aとＲ^15a、Ｒ^12aとＲ^15c、Ｒ^12cとＲ^14a、Ｒ^12cとＲ^14c、Ｒ^12cとＲ^15a、Ｒ^12cとＲ^15c、Ｒ^13aとＲ^15a、Ｒ^13aとＲ^15c、Ｒ^13cとＲ^15a、および／またはＲ^13cとＲ^15cは、一緒になってヘテロ原子を介在してもよいＣ２－Ｃ４架橋を形成してもよく、
および／または、Ｒ^11bとＲ^12b、Ｒ^11bとＲ^12c、Ｒ^11cとＲ^12b、Ｒ^11cとＲ^12c、Ｒ^12bとＲ^13b、Ｒ^12bとＲ^13c、Ｒ^12cとＲ^13b、Ｒ^12cとＲ^13c、Ｒ^13bとＲ^14b、Ｒ^13bとＲ^14c、Ｒ^13cとＲ^14b、Ｒ^13cとＲ^14c、Ｒ^14bとＲ^15b、Ｒ^14bとＲ^15c、Ｒ^14cとＲ^15b、および／またはＲ^14cとＲ^15cは、一緒になって結合を形成してもよく、
その他の記号は、前記［１］と同意義である）
［３］環Ｂが、以下のいずれかの式で示される、前記［１］または［２］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
式：

（式中、
Ｂ¹は、Ｃ、ＣＲ^11a、ＣＲ^11aＲ^11b、ＮＲ^11c、Ｎ、ＯまたはＳであり、
Ｂ²は、Ｃ、ＣＲ^12a、またはＮであり、
Ｂ³は、Ｃ、ＣＲ^13a、ＣＲ^13aＲ^13b、ＮＲ^13c、Ｎ、ＯまたはＳであり、
Ｂ⁴は、ＣＲ^14aＲ^14b、ＮＲ^14c、ＯまたはＳであり、
Ｂ⁵は、ＣＲ^15aＲ^15b、ＮＲ^15c、ＯまたはＳであり、
ただし、Ｂ¹およびＢ³が環Ｄの構成原子である場合は、Ｂ¹はＣ、ＣＲ^11aまたはＮであり、Ｂ³はＣ、ＣＲ^13aまたはＮであり、
Ｒ^11a、Ｒ^12a、Ｒ^13a、Ｒ^14a、およびＲ^15aは、それぞれ独立して、水素、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｒ^11b、Ｒ^12b、Ｒ^13b、Ｒ^14b、およびＲ^15bは、それぞれ独立して、水素、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｒ^11c、Ｒ^12c、Ｒ^13c、Ｒ^14c、およびＲ^15cは、それぞれ独立して、水素、シアノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルであり、
または、Ｒ^11aとＲ^13a、Ｒ^11aとＲ^13c、Ｒ^11aとＲ^14a、Ｒ^11aとＲ^14c、Ｒ^11aとＲ^15a、Ｒ^11aとＲ^15c、Ｒ^11cとＲ^13a、Ｒ^11cとＲ^13c、Ｒ^11cとＲ^14a、Ｒ^11cとＲ^14c、Ｒ^11cとＲ^15a、Ｒ^11cとＲ^15c、Ｒ^12aとＲ^14a、Ｒ^12aとＲ^14c、Ｒ^12aとＲ^15a、Ｒ^12aとＲ^15c、Ｒ^12cとＲ^14a、Ｒ^12cとＲ^14c、Ｒ^12cとＲ^15a、Ｒ^12cとＲ^15c、Ｒ^13aとＲ^15a、Ｒ^13aとＲ^15c、Ｒ^13cとＲ^15a、および／またはＲ^13cとＲ^15cは、一緒になってヘテロ原子を介在してもよいＣ２－Ｃ４架橋を形成してもよく、
および／または、Ｒ^11bとＲ^12b、Ｒ^11bとＲ^12c、Ｒ^11cとＲ^12b、Ｒ^11cとＲ^12c、Ｒ^12bとＲ^13b、Ｒ^12bとＲ^13c、Ｒ^12cとＲ^13b、Ｒ^12cとＲ^13c、Ｒ^13bとＲ^14b、Ｒ^13bとＲ^14c、Ｒ^13cとＲ^14b、Ｒ^13cとＲ^14c、Ｒ^14bとＲ^15b、Ｒ^14bとＲ^15c、Ｒ^14cとＲ^15b、および／またはＲ^14cとＲ^15cは、一緒になって結合を形成してもよく、
環Ｄは、芳香族炭素環、非芳香族炭素環、芳香族複素環、または非芳香族複素環であり、
Ｒ⁶は、それぞれ独立して、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
ｎは、１～４の整数であり、
その他の記号は、前記［１］と同意義である）
［４］環Ｂが、以下のいずれかの式で示される、前記［１］～［３］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
式：

（式中、Ｂ¹、Ｂ³、Ｂ⁴、Ｂ⁵、Ｒ⁶およびｎは、前記［３］と同意義である）
［５］Ｒ⁶が、それぞれ独立して、ハロゲン、シアノ、ヒドロキシ、置換もしくは非置換のアミノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のスルファモイル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の非芳香族炭素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルである、前記［３］または［４］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［６］環Ｃが、芳香族炭素環または芳香族複素環である、前記［１］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［７］Ｒ⁵が、それぞれ独立して、ハロゲン、シアノ、ヒドロキシ、置換もしくは非置換のアミノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のスルファモイル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の非芳香族炭素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルであり、
ｎが１～３である、前記［１］または［６］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［８］Ｒ^2bが、置換もしくは非置換のアルキルである、前記［１］、［６］または［７］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［９］Ｒ^4aが、以下に示される基である、前記［１］～［８］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。

（式中、
Ｌ¹は、単結合または置換もしくは非置換のアルキレンであり、
Ｌ²は、－Ｎ（Ｈ）－、－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｏ－、－Ｏ－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｎ（Ｈ）－、－Ｎ（Ｈ）－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－、または－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－であり、
Ｌ³は、単結合または置換もしくは非置換のアルキレンであり、
Ｒ⁷は、水素、ハロゲン、ヒドロキシ、シアノ、置換もしくは非置換のアミノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、式：－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1であり、および
その他の記号は、前記［１］と同意義である）。
［１０］Ｒ^4bが、置換もしくは非置換のアルキル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、または置換もしくは非置換の非芳香族複素環式基である、前記［１］～［９］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［１１］Ｒ^3aおよびＲ^3bが水素である、前記［１］～［１０］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［１２］化合物Ｉ－８、Ｉ－１０、Ｉ－１２、Ｉ－２３、Ｉ－２４、Ｉ－３４、Ｉ－６７、Ｉ－１７０、Ｉ－１９０、Ｉ－２１２、Ｉ－２３６、Ｉ－２５３、Ｉ－２７５、Ｉ－２７６、ＩＩ－９３、ＩＩ－９４、ＩＩ－１０３、ＩＩ－１２１、ＩＩ－１５１、ＩＩ－１６８、ＩＩ－１７４、ＩＩ－２０３、ＩＩ－２２５、ＩＩ－２３３、ＩＩ－２７０、ＩＩ－２７６およびＩＩ－２９５からなる群から選択される、前記［１］記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
［１２－１］化合物Ｉ－９、Ｉ－７２、Ｉ－９７、Ｉ－１００、Ｉ－１０４、Ｉ－１１０、Ｉ－１２２、Ｉ－１３１、Ｉ－１３３、Ｉ－１６３、Ｉ－１６７、Ｉ－１６８、Ｉ－１８６、Ｉ－１９３、Ｉ－２００、Ｉ－２４２、Ｉ－２８０、Ｉ－２８４、ＩＩ－６７、ＩＩ－７２、ＩＩ－８７、ＩＩ－１３７、ＩＩ－１４７、ＩＩ－２０１、ＩＩ－２０２、ＩＩ－２１４、ＩＩ－２３８、ＩＩ－２６２、ＩＩ－２７３およびＩＩ－２７４からなる群から選択される、前記［１］記載の化合物またはその製薬上許容される塩、を含有する医薬組成物。
［１３］式（Ｉ）：

（式中、
式：

で示される部分が

であり；
Ｘは、Ｃ（＝Ｏ）であり；
Ｒ¹は、水素であり；
Ｒ^2aは、式：

（式中、環Ｃは、ベンゼンまたはピリジンであり；
Ｒ⁵は、それぞれ独立して、ハロゲン、ハロアルキル、ハロアルキルオキシ、ハロゲンまたはハロアルキルで置換されてもよい非芳香族炭素環式基、またはハロゲンまたはハロアルキルで置換されてもよい非芳香族複素環式基であり、
ｎは、１～３の整数である）であり、
Ｒ^2bは、アルキル、またはハロアルキルであり、または
Ｒ^2aおよびＲ^2bは、隣接する炭素原子と一緒になって、環Ｂを形成してもよく、
環Ｂは、式：

（式中、Ｒ⁶は、それぞれ独立して、ハロゲン、ハロアルキル、ハロアルキルオキシ、ハロゲンまたはハロアルキルで置換されてもよい非芳香族炭素環式基、またはハロゲンまたはハロアルキルで置換されてもよい非芳香族複素環式基であり、
Ｒ^14aおよびＲ^14bは、それぞれ独立して、水素またはハロゲンであり、
ｎは、１～３の整数である）であり；
Ｒ^3aは、水素であり、
Ｒ^3bは、水素であり；
Ｒ^4aは、カルボキシまたは式：

であり；
Ｌ³は、単結合またはアルキレンであり、
Ｒ⁷は、水素、ハロゲン、アルキルスルホニル、オキソで置換されていてもよい非芳香族複素環式基、アルキルで置換されていてもよい非芳香族炭素環スルホニル、または式：－Ｓ（＝Ｏ）（＝Ｎ－Ｈ）－Ｒ^S1であり、
Ｒ^4bは、置換基群αで置換されていてもよいアルキル、置換基群βで置換されていてもよい芳香族炭素環式基、または置換基群βで置換されていてもよい芳香族複素環式基であり、
Ｒ^S1は、アルキルであり、
置換基群αは、ハロゲン、ハロアルキルオキシ、および非芳香族炭素環式基であり、
置換基群βは、ハロゲン、シアノ、アルキル、ハロアルキル、およびアルキルオキシである）で示される化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［１４］ＭＧＡＴ２阻害作用を有する、前記［１］～［１３］または［１２－１］のいずれかに記載の医薬組成物。
［１５］ＭＧＡＴ２の関与する疾患の治療または予防のために用いる、前記［１４］記載の医薬組成物。
［１６］肥満症、メタボリックシンドローム、高脂血症、高中性脂肪血症、高ＶＬＤＬ血症、高脂肪酸血症、糖尿病または動脈硬化症の治療または予防のために用いる、前記［１５］記載の医薬組成物。 [1] Equation (I):

(During the ceremony,
formula:

The part indicated by

And;
X is C (= O), C (= S), or SO ₂ ;
m is 0 or 1;

R ¹ is hydrogen, hydroxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted. Substituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or non-substituted Substituted aromatic carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, substituted or unsubstituted non-aromatic heterocyclic carbonyls, substituted or unsubstituted aromatics Carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic A carbocyclic sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic sulfonyl, a substituted or unsubstituted aromatic heterocyclic sulfonyl, or a substituted or unsubstituted non-aromatic heterocyclic sulfonyl, wherein R ¹ is the formula:

Not;

R ^2a is the formula:

(In the formula, ring C is an aromatic carbocycle, an aromatic heterocycle, a non-aromatic carbocycle, or a non-aromatic heterocycle;
R ⁵ are independently halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted. Ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted. Alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted Alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted Alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups. Formula groups, substituted or unsubstituted aromatic carbocyclic oxys, substituted or unsubstituted non-aromatic carbocyclic oxys, substituted or unsubstituted aromatic heterocyclic oxys, substituted or unsubstituted non-aromatic heterocyclic oxys, substituted Alternatively, unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted. Alternatively, an unsubstituted or unsubstituted aromatic carbocyclic carbonyl, a substituted or unsubstituted non-aromatic carbocyclic carbonyl, a substituted or unsubstituted aromatic heterocyclic carbonyl, a substituted or unsubstituted non-aromatic heterocyclic carbonyl, a substituted or unsubstituted. Aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted Aromatic carbocyclic sulfanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or Unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic Group heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl , Substituted or unsubstituted non-aromatic heterocyclic sulfonyl, Formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN ) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (= ^N - ^RN ) ₂ -RS1.
n is an integer from 1 to 5)
R ^2b is cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted alkylsulfonyl, or R ^2a and R. ^2b may be combined with adjacent carbon atoms to form ring B.
Ring B is a substituted or unsubstituted non-aromatic carbocycle or a substituted or unsubstituted non-aromatic heterocycle;

R ^3a is hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted. Substituent non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic group oxy, substituted or Unsubstituted non-aromatic carbocyclic group oxy, substituted or unsubstituted aromatic heterocyclic group oxy, substituted or unsubstituted non-aromatic heterocyclic group oxy, substituted or unsubstituted aromatic carbocyclic group A sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic group sulfonyl, a substituted or unsubstituted aromatic heterocyclic group sulfonyl, or a substituted or unsubstituted non-aromatic heterocyclic group sulfonyl.
R ^3b is hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted. Substituent non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic group oxy, substituted or Unsubstituted non-aromatic carbocyclic group oxy, substituted or unsubstituted aromatic heterocyclic group oxy, substituted or unsubstituted non-aromatic heterocyclic group oxy, substituted or unsubstituted aromatic carbocyclic group A sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic group sulfonyl, a substituted or unsubstituted aromatic heterocyclic group sulfonyl, or a substituted or unsubstituted non-aromatic heterocyclic group sulfonyl.
R ^3a and R ^3b may be combined with adjacent carbon atoms to form a substituted or unsubstituted non-aromatic carbon ring or a substituted or unsubstituted non-aromatic heterocycle, or R ^2b and R. ^3b may be combined with adjacent carbon atoms to form a substituted or unsubstituted non-aromatic carbon ring or a substituted or unsubstituted non-aromatic heterocycle;

R ^4a is the formula:

And;
L ¹ is a single bond or substituted or unsubstituted alkylene,
L ² is a single bond, -C (= O)-, -C (= O) -O-, -OC (= O)-, -N (H)-, -C (= O) -N. (H)-, -N (H) -C (= O)-, -N (H) -C (= O) -N (H)-, -C (= O) -N (H) -S ( = O) _2- , -N (H) -S (= O) _2- , -S (= O) ₂ -N (H)-, -N (H) -S (= O) ₂ -N (H) )-Or-S (= O) ₂ -N (H) -C (= O)-,
L ³ is a single bond or substituted or unsubstituted alkylene,
R ⁷ is hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, Substituent or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyl Oxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted Alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted aromatic Carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatics. Carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy. , Substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbocyclic carbonyl, Substituent or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or non-substituted Substituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfanyl, substituted or unsubstituted. Non-aromatic carousyl sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted if Or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted. Non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic Heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or the formula: -S (= ^N - ^RN ) ₂ -RS1.
However, if L ¹ , L ² , and L ³ are single bonds, then R ⁷ is not hydrogen or halogen,
R ^4b is halogen, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted. Guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted. Alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or Unsubstituted alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted. Aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted. Aromatic carbon ring oxy, substituted or unsubstituted non-aromatic carbon ring oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbon Ring carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbon Ring carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, Substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfanyl, substituted Or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfa Nyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or Unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or the formula: -S (= ^N - ^RN ) ₂ -RS1.
R ^4c'is hydrogen, halogen, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted. Alternatively, unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted. Alternatively, unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl. , Substituted or unsubstituted alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted. Alternatively, an unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted non-aromatic heterocyclic group, a substituted. Alternatively, an unsubstituted aromatic carbocyclic oxy, a substituted or unsubstituted non-aromatic carbon ring oxy, a substituted or unsubstituted aromatic heterocyclic oxy, a substituted or unsubstituted non-aromatic heterocyclic oxy, a substituted or unsubstituted. Aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted Aromatic carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, substituted or unsubstituted non-aromatic heterocyclic carbonyls, substituted or unsubstituted aromatic carbocycles. Oxycarbonyl, substituted or unsubstituted non-aromatic carbocycle oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocycle Sulfanyl, substituted or unsubstituted non-aromatic carbocycle Sulfanyl, substituted or unsubstituted aromatic heterocycle Sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or Unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or the formula: -S (= ^N - ^RN ) ₂ -RS1.
L is independently single bond, alkylene, or C (= O), respectively.
R ^S1 and R ^S2 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted. An aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, or
RS1 and ^RS2 bonded to the same sulfur atom may be combined with the sulfur atom to form a substituted or ^{unsubstituted} non-aromatic heterocycle;
^RNs are independently hydrogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aromatics. Group carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatics. Compounds represented by group carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, or substituted or unsubstituted non-aromatic heterocyclic carbonyls, (provided that they are. , Excluding the following compounds

) Or a pharmaceutically acceptable salt thereof, a pharmaceutical composition.
[2] A pharmaceutical composition in which ring B contains the compound according to the above [1] or a pharmaceutically acceptable salt thereof, which is represented by any of the following formulas.
formula:

(During the ceremony,
B ¹ is CR ^11a R ^11b , NR ^11c , O, or S.
B ² is CR ^12a R ^12b , NR ^12c , O, or S.
B ³ is CR ^13a R ^13b , NR ^13c , O, or S.
B ⁴ is CR ^14a R ^14b , NR ^14c , O, or S, and B ⁵ is CR ^15a R ^15b , NR ^15c , O, or S.
R ^11a , R ^12a , R ^13a , R ^14a , and R ^15a are independently hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or non-substituted, respectively. Substituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted. Alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenyl Carbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenyl Sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocycles. Oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy , Substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or Unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or non-substituted Substituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocycles Rufanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or Unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (=) ^N -RN) ₂ - ^RS1 is a group represented by
R ^11b , R ^12b , R ^13b , R ^14b , and R ^15b are independently hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or non-substituted, respectively. Substituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted. Alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenyl Carbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenyl Sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocycles. Oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy , Substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or Unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or non-substituted Substituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocycles Rufanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or Unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (=) ^N -RN) ₂ - ^RS1 is a group represented by
R ^11c , R ^12c , R ^13c , R ^14c , and R ^15c are independently hydrogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or Unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkenyl, substituted or unsubstituted. Alkoxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted. Alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted fragrance. Group carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatics. Group carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyl , Substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or Unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfanyl, substituted or non-substituted Substituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic Group Carbocyclic Sulfinyl, Substituted or unsubstituted Aromatic Heterocyclic Sulfinyl, Substituted or unsubstituted Non-Aromatic Heterocyclic Sulfinyl Finyl, substituted or unsubstituted aromatic carbocyclic sulfonyls, substituted or unsubstituted non-aromatic carbocyclic sulfonyls, substituted or unsubstituted aromatic heterocyclic sulfonyls, or substituted or unsubstituted non-aromatic heterocyclic sulfonyls. ,
Alternatively, R ^11a and R ^12a , R ^12a and R ^13a , R ^13a and R ^14a , and / or R ^14a and R ^15a , together with adjacent carbon atoms, are substituted or unsubstituted aromatic carbon rings, Substituted or unsubstituted non-aromatic carbocycles, substituted or unsubstituted aromatic heterocycles, or substituted or unsubstituted non-aromatic heterocycles may be formed.
And / or R ^11c and R ^12a , R ^11c and R ^12c , R ^12c and R ^11a , R ^12c and R ^13a , R ^12c and R ^13c , R ^13c and R ^12a , R ^13c and R ^14a , R ^13c and R ^14c , R ^14c and R ^13a , R ^14c and R ^15a , R ^14c and R ^15c , and / or R ^15c and R ^14a , together with adjacent atoms, are substituted or unsubstituted aromatic heterocycles or substitutions. Alternatively, an unsubstituted non-aromatic heterocycle may be formed.
And / or R ^11a and R ^13a , R ^11a and R ^13c , R ^11a and R ^14a , R ^11a and R ^14c , R ^11a and R ^15a , R ^11a and R ^15c , R ^11c and R ^13a , R ^11c and R ^13c , R ^11c and R ^14a , R ^11c and R ^14c , R ^11c and R ^15a , R ^11c and R ^15c , R ^12a and R ^14a , R ^12a and R ^14c , R ^12a and R ^15a , R ^12a and R ^15c , R ^12c and R ^14a , R ^12c and R ^14c , R ^12c and R ^15a , R ^12c and R ^15c , R ^13a and R ^15a , R ^13a and R ^15c , R ^13c and R ^15a , and / or R ^13c and R ^15c . May together form a C2-C4 crosslink that may intervene heteroatoms.
And / or R ^11b and R ^12b , R ^11b and R ^12c , R ^11c and R ^12b , R ^11c and R ^12c , R ^12b and R ^13b , R ^12b and R ^13c , R ^12c and R ^13b , R ^12c and R ^13c , R ^13b and R ^14b , R ^13b and R ^14c , R ^13c and R ^14b , R ^13c and R ^14c , R ^14b and R ^15b , R ^14b and R ^15c , R ^14c and R ^15b , and / or R ^14c . R ^15c may be combined to form a bond,
Other symbols have the same meaning as [1] above)
[3] A pharmaceutical composition in which ring B contains the compound according to the above [1] or [2], or a pharmaceutically acceptable salt thereof, which is represented by any of the following formulas.
formula:

(During the ceremony,
B ¹ is C, CR ^11a , CR ^11a R ^11b , NR ^11c , N, O or S.
B ² is C, CR ^12a , or N,
B ³ is C, CR ^13a , CR ^13a R ^13b , NR ^13c , N, O or S.
B ⁴ is CR ^14a R ^14b , NR ^14c , O or S,
B ⁵ is CR ^15a R ^15b , NR ^15c , O or S,
However, when B ¹ and B ³ are constituent atoms of ring D, B ¹ is C, CR ^11a or N, and B ³ is C, CR ^13a or N.
R ^11a , R ^12a , R ^13a , R ^14a , and R ^15a are independently hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or non-substituted, respectively. Substituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted. Alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenyl Carbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenyl Sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocycles. Oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy , Substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or Unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or non-substituted Substituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocycles Rufanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or Unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (=) ^N -RN) ₂ - ^RS1 is a group represented by
R ^11b , R ^12b , R ^13b , R ^14b , and R ^15b are independently hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or non-substituted, respectively. Substituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted. Alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenyl Carbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenyl Sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocycles. Oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy , Substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or Unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or non-substituted Substituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocycles Rufanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or Unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (=) ^N -RN) ₂ - ^RS1 is a group represented by
R ^11c , R ^12c , R ^13c , R ^14c , and R ^15c are independently hydrogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or Unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkenyl, substituted or unsubstituted. Alkoxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted. Alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted fragrance. Group carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatics. Group carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyl , Substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or Unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfanyl, substituted or non-substituted Substituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic Group Carbocyclic Sulfinyl, Substituted or unsubstituted Aromatic Heterocyclic Sulfinyl, Substituted or unsubstituted Non-Aromatic Heterocyclic Sulfinyl Finyl, substituted or unsubstituted aromatic carbocyclic sulfonyls, substituted or unsubstituted non-aromatic carbocyclic sulfonyls, substituted or unsubstituted aromatic heterocyclic sulfonyls, or substituted or unsubstituted non-aromatic heterocyclic sulfonyls. ,
Or R ^11a and R ^13a , R ^11a and R ^13c , R ^11a and R ^14a , R ^11a and R ^14c , R ^11a and R ^15a , R ^11a and R ^15c , R ^11c and R ^13a , R ^11c and R ^13c , R ^11c and R ^14a , R ^11c and R ^14c , R ^11c and R ^15a , R ^11c and R ^15c , R ^12a and R ^14a , R ^12a and R ^14c , R ^12a and R ^15a , R ^12a and R ^15c , R ^12c And R ^14a , R ^12c and R ^14c , R ^12c and R ^15a , R ^12c and R ^15c , R ^13a and R ^15a , R ^13a and R ^15c , R ^13c and R ^15a , and / or R ^13c and R ^15c . Together they may form C2-C4 crosslinks that may intervene heteroatoms.
And / or R ^11b and R ^12b , R ^11b and R ^12c , R ^11c and R ^12b , R ^11c and R ^12c , R ^12b and R ^13b , R ^12b and R ^13c , R ^12c and R ^13b , R ^12c and R ^13c , R ^13b and R ^14b , R ^13b and R ^14c , R ^13c and R ^14b , R ^13c and R ^14c , R ^14b and R ^15b , R ^14b and R ^15c , R ^14c and R ^15b , and / or R ^14c . R ^15c may be combined to form a bond,
Ring D is an aromatic carbocycle, a non-aromatic carbocycle, an aromatic heterocycle, or a non-aromatic heterocycle.
R ⁶ are independently halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted. Ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted. Alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted Alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted Alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups. Formula groups, substituted or unsubstituted aromatic carbocyclic oxys, substituted or unsubstituted non-aromatic carbocyclic oxys, substituted or unsubstituted aromatic heterocyclic oxys, substituted or unsubstituted non-aromatic heterocyclic oxys, substituted Alternatively, unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted. Alternatively, an unsubstituted or unsubstituted aromatic carbocyclic carbonyl, a substituted or unsubstituted non-aromatic carbocyclic carbonyl, a substituted or unsubstituted aromatic heterocyclic carbonyl, a substituted or unsubstituted non-aromatic heterocyclic carbonyl, a substituted or unsubstituted. Aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted Aromatic carbocyclic sulfanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or Unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic Group heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl , Substituted or unsubstituted non-aromatic heterocyclic sulfonyl, Formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN ) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (= ^N - ^RN ) ₂ -RS1.
n is an integer of 1 to 4 and
Other symbols have the same meaning as [1] above)
[4] A pharmaceutical composition in which ring B contains the compound according to any one of the above [1] to [3], or a pharmaceutically acceptable salt thereof, which is represented by any of the following formulas.
formula:

(In the formula, B ¹ , B ³ , B ⁴ , B ⁵ , R ⁶ and n have the same meaning as [3] above).
[5] R ⁶ are independently halogen, cyano, hydroxy, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted carbamoyl, substituted or non-substituted. Substituted sulfamoyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic complex Cyclic group, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, or substituted or unsubstituted non-aromatic complex A pharmaceutical composition containing the compound according to the above [3] or [4], which is a ring sulfonyl, or a pharmaceutically acceptable salt thereof.
[6] A pharmaceutical composition containing the compound according to the above [1], or a pharmaceutically acceptable salt thereof, wherein the ring C is an aromatic carbocycle or an aromatic heterocycle.
[7] R ⁵ are independently halogen, cyano, hydroxy, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted carbamoyl, substituted or non-substituted. Substituted sulfamoyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic complex A cyclic group, a substituted or unsubstituted non-aromatic carbocyclic oxy, a substituted or unsubstituted non-aromatic heterocyclic oxy, a substituted or unsubstituted non-aromatic carbocyclic sulfonyl, or a substituted or unsubstituted non-aromatic complex. It is a ring sulfonyl and
A pharmaceutical composition containing the compound according to the above [1] or [6], or a pharmaceutically acceptable salt thereof, wherein n is 1 to 3.
[8] A pharmaceutical composition containing the compound according to any one of the above [1], [6] or [7], or a pharmaceutically acceptable salt thereof, wherein R ^2b is a substituted or unsubstituted alkyl. thing.
[9] A pharmaceutical composition in which R ^4a contains the compound according to any one of the above [1] to [8], or a pharmaceutically acceptable salt thereof, which is a group shown below.

(During the ceremony,
L ¹ is a single bond or substituted or unsubstituted alkylene,
L ² is -N (H)-, -C (= O)-, -C (= O) -O-, -OC (= O)-, -C (= O) -N (H). -, -N (H) -C (= O)-, -C (= O) -N (H) -S (= O) _2- , or -N (H) -S (= O) _2- can be,
L ³ is a single bond or substituted or unsubstituted alkylene,
R ⁷ is hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyl sulfanyl, substituted. Alternatively, an unsubstituted alkyl sulphinyl, a substituted or unsubstituted alkylsulfonyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group. Group, substituted or unsubstituted non-aromatic heterocyclic group, formula: -N = S (= O) ( ^-RS1 ) ^-RS2 , or formula: -S (= O) (= ^N -RN) ^-RS1 and other symbols have the same meaning as [1] above).
[10] R ^4b is a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group. , Or a pharmaceutical composition containing a substituted or unsubstituted non-aromatic heterocyclic group, the compound according to any one of the above [1] to [9], or a pharmaceutically acceptable salt thereof.
[11] A pharmaceutical composition containing the compound according to any one of the above [1] to [10], or a pharmaceutically acceptable salt thereof, wherein R ^3a and R ^3b are hydrogen.
[12] Compounds I-8, I-10, I-12, I-23, I-24, I-34, I-67, I-170, I-190, I-212, I-236, I- 253, I-275, I-276, II-93, II-94, II-103, II-121, II-151, II-168, II-174, II-203, II-225, II-233, A pharmaceutical composition containing the compound according to the above [1] or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of II-270, II-276 and II-295.
[12-1] Compounds I-9, I-72, I-97, I-100, I-104, I-110, I-122, I-131, I-133, I-163, I-167, I-168, I-186, I-193, I-200, I-242, I-280, I-284, II-67, II-72, II-87, II-137, II-147, II- The compound according to [1] above or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of 201, II-202, II-214, II-238, II-262, II-273 and II-274. The pharmaceutical composition contained.
[13] Equation (I):

(During the ceremony,
formula:

The part indicated by

And;
X is C (= O);
R ¹ is hydrogen;
R ^2a is the formula:

(In the formula, ring C is benzene or pyridine;
Each of R ⁵ is independently a non-aromatic carbocyclic group which may be substituted with halogen, haloalkyl, haloalkyloxy, halogen or haloalkyl, or a non-aromatic heterocyclic group which may be substituted with halogen or haloalkyl. And
n is an integer of 1 to 3)
R ^2b may be alkyl or haloalkyl, or R ^2a and R ^2b may be combined with adjacent carbon atoms to form ring B.
Ring B is the formula:

(In the formula, R ⁶ is a non-aromatic carbocyclic group which may be independently substituted with halogen, haloalkyl, haloalkyloxy, halogen or haloalkyl, or a non-aromatic group which may be substituted with halogen or haloalkyl. It is a heterocyclic group and
R ^14a and R ^14b are independently hydrogen or halogen, respectively.
n is an integer of 1 to 3);
R ^3a is hydrogen,
R ^3b is hydrogen;
R ^4a is carboxy or formula:

And;
L ³ is single bond or alkylene and
R ⁷ is a non-aromatic heterocyclic group optionally substituted with hydrogen, halogen, alkyl sulfonyl, oxo, a non-aromatic carbocyclic sulfonyl optionally substituted with alkyl, or the formula: —S (= O). ) (= NH) ^-RS1
R ^4b is an alkyl substituted with a substituent group α, an aromatic carbocyclic group optionally substituted with a substituent group β, or an aromatic complex optionally substituted with a substituent group β. It is a cyclic group and
^RS1 is alkyl and
Substituents α are halogen, haloalkyloxy, and non-aromatic carbocyclic groups.
Substituent group β is a compound represented by halogen, cyano, alkyl, haloalkyl, and alkyloxy), or a pharmaceutically acceptable salt thereof, which is a pharmaceutical composition.
[14] The pharmaceutical composition according to any one of the above [1] to [13] or [12-1], which has an MGAT2 inhibitory action.
[15] The pharmaceutical composition according to the above [14], which is used for the treatment or prevention of a disease associated with MGAT2.
[16] The above-mentioned [15], which is used for the treatment or prevention of obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, hyperfatty acidemia, diabetes or arteriosclerosis. Pharmaceutical composition.

（式中、
環Ａは、ベンゼン環、または５員もしくは６員の芳香族複素環であり、
Ｚ¹は、Ｃ、またはＮであり、
Ｚ²は、Ｃ、またはＮであり、
破線は結合の存在、非存在を表し、結合が存在する場合は、Ｚ¹はＣであり、Ｚ²は、Ｃであり、
Ｘは、Ｃ（＝Ｏ）、Ｃ（＝Ｓ）、またはＳＯ₂であり、

Ｒ¹は、水素、ヒドロキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルであり、
ただしＲ¹は、式：

でなく；

Ｒ^2aおよびＲ^2bは、隣接する炭素原子と一緒になって、環Ｂを形成し、
環Ｂは、置換もしくは非置換の非芳香族炭素環または置換もしくは非置換の非芳香族複素環であり、
ただし、環Ａが５員の芳香族複素環の場合、Ｒ^2aは、式：

であってもよく、Ｒ^2bは、水素、シアノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキニル、または置換もしくは非置換のアルキルスルホニルであってもよい、
環Ｃは、芳香族炭素環、芳香族複素環、非芳香族複素環、または炭素数４～１６の非芳香族炭素環であり、
Ｒ⁵は、それぞれ独立して、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
ｎは、１～５の整数であり；

Ｒ^3aは、水素、ハロゲン、ヒドロキシ、シアノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環式基オキシ、置換もしくは非置換の非芳香族炭素環式基オキシ、置換もしくは非置換の芳香族複素環式基オキシ、置換もしくは非置換の非芳香族複素環式基オキシ、置換もしくは非置換の芳香族炭素環式基スルホニル、置換もしくは非置換の非芳香族炭素環式基スルホニル、置換もしくは非置換の芳香族複素環式基スルホニル、または置換もしくは非置換の非芳香族複素環式基スルホニルであり、
Ｒ^3bは、水素、ハロゲン、ヒドロキシ、シアノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環式基オキシ、置換もしくは非置換の非芳香族炭素環式基オキシ、置換もしくは非置換の芳香族複素環式基オキシ、置換もしくは非置換の非芳香族複素環式基オキシ、置換もしくは非置換の芳香族炭素環式基スルホニル、置換もしくは非置換の非芳香族炭素環式基スルホニル、置換もしくは非置換の芳香族複素環式基スルホニル、または置換もしくは非置換の非芳香族複素環式基スルホニルであり、または
Ｒ^3aとＲ^3bは、隣接する炭素原子と一緒になって、置換もしくは非置換の非芳香族炭素環または置換もしくは非置換の非芳香族複素環を形成してもよく；

Ｒ^4aは、式：

Ｌ¹は、単結合または置換もしくは非置換のアルキレンであり、
Ｌ²は、単結合、－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｏ－、－Ｏ－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｎ（Ｈ）－、－Ｎ（Ｈ）－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－、－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－、－Ｓ（＝Ｏ）₂－Ｎ（Ｈ）－、または－Ｓ（＝Ｏ）₂－Ｎ（Ｈ）－Ｃ（＝Ｏ）－であり、
Ｌ³は、単結合または置換もしくは非置換のアルキレンであり、
Ｒ⁷は、水素、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
ただし、Ｌ¹、Ｌ²、およびＬ³が単結合の場合は、Ｒ⁷は、水素、またはヒドロキシではなく、
Ｒ^4bは、ハロゲン、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｒ^4cは、それぞれ独立して、ハロゲン、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
ただしＲ^4a、Ｒ^4b、およびＲ^4cは、ベンジルオキシ、メチルオキシおよびメチルスルファニルではなく；
ｍは、０～３の整数であり、
Ｌは、それぞれ独立して、単結合、アルキレン、またはＣ（＝Ｏ）であり、
Ｒ^S1およびＲ^S2は、それぞれ独立して、水素、置換もしくは非置換のアルキル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、または置換もしくは非置換の非芳香族複素環式基であり、または、
同一の硫黄原子に結合しているＲ^S1およびＲ^S2は当該硫黄原子と一緒になって置換もしくは非置換の非芳香族複素環を形成してもよく；
Ｒ^Nは、それぞれ独立して、水素、シアノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、または置換もしくは非置換の非芳香族複素環カルボニルである）
で示される化合物、
（ただし、以下の化合物を除く

）またはその製薬上許容される塩、を含有する医薬組成物。
［２’］式：

で示される部分が

（式中、
Ｒ^4c’が水素、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルであり、
その他の各記号は前記［１’］と同意義である）
で示される、前記［１’］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［３’］環Ｂが、以下のいずれかの式で示される、前記［１’］または［２’］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
式：

（式中、
Ｂ¹は、ＣＲ^11aＲ^11b、ＮＲ^11c、Ｏ、またはＳであり、
Ｂ²は、ＣＲ^12aＲ^12b、ＮＲ^12c、Ｏ、またはＳであり、
Ｂ³は、ＣＲ^13aＲ^13b、ＮＲ^13c、Ｏ、またはＳであり、
Ｂ⁴は、ＣＲ^14aＲ^14b、ＮＲ^14c、Ｏ、またはＳであり、および
Ｂ⁵は、ＣＲ^15aＲ^15b、ＮＲ^15c、Ｏ、またはＳであり、
Ｒ^11a、Ｒ^12a、Ｒ^13a、Ｒ^14a、およびＲ^15aは、それぞれ独立して、水素、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｒ^11b、Ｒ^12b、Ｒ^13b、Ｒ^14b、およびＲ^15bは、それぞれ独立して、水素、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
Ｒ^11c、Ｒ^12c、Ｒ^13c、Ｒ^14c、およびＲ^15cは、それぞれ独立して、水素、シアノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルであり、
または、Ｒ^11aとＲ^12a、Ｒ^12aとＲ^13a、Ｒ^13aとＲ^14a、および／またはＲ^14aとＲ^15aは、隣接する炭素原子と一緒になって、置換もしくは非置換の芳香族炭素環、置換もしくは非置換の非芳香族炭素環、置換もしくは非置換の芳香族複素環、または置換もしくは非置換の非芳香族複素環を形成してもよく、
および／または、Ｒ^11cとＲ^12a、Ｒ^11cとＲ^12c、Ｒ^12cとＲ^11a、Ｒ^12cとＲ^13a、Ｒ^12cとＲ^13c、Ｒ^13cとＲ^12a、Ｒ^13cとＲ^14a、Ｒ^13cとＲ^14c、Ｒ^14cとＲ^13a、Ｒ^14cとＲ^15a、Ｒ^14cとＲ^15c、および／またはＲ^15cとＲ^14aは、隣接する原子と一緒になって、置換もしくは非置換の芳香族複素環または置換もしくは非置換の非芳香族複素環を形成してもよく、
および／または、Ｒ^11aとＲ^13a、Ｒ^11aとＲ^13c、Ｒ^11aとＲ^14a、Ｒ^11aとＲ^14c、Ｒ^11aとＲ^15a、Ｒ^11aとＲ^15c、Ｒ^11cとＲ^13a、Ｒ^11cとＲ^13c、Ｒ^11cとＲ^14a、Ｒ^11cとＲ^14c、Ｒ^11cとＲ^15a、Ｒ^11cとＲ^15c、Ｒ^12aとＲ^14a、Ｒ^12aとＲ^14c、Ｒ^12aとＲ^15a、Ｒ^12aとＲ^15c、Ｒ^12cとＲ^14a、Ｒ^12cとＲ^14c、Ｒ^12cとＲ^15a、Ｒ^12cとＲ^15c、Ｒ^13aとＲ^15a、Ｒ^13aとＲ^15c、Ｒ^13cとＲ^15a、および／またはＲ^13cとＲ^15cは、一緒になってヘテロ原子を介在してもよいＣ２－Ｃ４架橋を形成してもよく、
および／または、Ｒ^11bとＲ^12b、Ｒ^11bとＲ^12c、Ｒ^11cとＲ^12b、Ｒ^11cとＲ^12c、Ｒ^12bとＲ^13b、Ｒ^12bとＲ^13c、Ｒ^12cとＲ^13b、Ｒ^12cとＲ^13c、Ｒ^13bとＲ^14b、Ｒ^13bとＲ^14c、Ｒ^13cとＲ^14b、Ｒ^13cとＲ^14c、Ｒ^14bとＲ^15b、Ｒ^14bとＲ^15c、Ｒ^14cとＲ^15b、および／またはＲ^14cとＲ^15cは、一緒になって結合を形成してもよく、
破線は結合の存在または非存在を示し、
その他の記号は、前記［１’］と同意義である）
［４’］環Ｂが、以下のいずれかの式で示される、前記［１’］～［３’］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
式：

（式中、
環Ｄは、芳香族炭素環、非芳香族炭素環、芳香族複素環、または非芳香族複素環であり、
Ｒ⁶は、それぞれ独立して、ハロゲン、ヒドロキシ、シアノ、カルボキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のチオカルバモイル、置換もしくは非置換のアミジノ、置換もしくは非置換のアミノ、置換もしくは非置換のウレイド、置換もしくは非置換のグアニジノ、ペンタフルオロチオ、スルホ、置換もしくは非置換のスルファモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルケニルオキシ、置換もしくは非置換のアルキルカルボニルオキシ、置換もしくは非置換のアルケニルカルボニルオキシ、置換もしくは非置換のアルキルカルボニル、置換もしくは非置換のアルケニルカルボニル、置換もしくは非置換のアルキルオキシカルボニル、置換もしくは非置換のアルケニルオキシカルボニル、置換もしくは非置換のアルキルスルファニル、置換もしくは非置換のアルケニルスルファニル、置換もしくは非置換のアルキルスルフィニル、置換もしくは非置換のアルケニルスルフィニル、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルケニルスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の芳香族炭素環オキシ、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の芳香族複素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の芳香族炭素環カルボニルオキシ、置換もしくは非置換の非芳香族炭素環カルボニルオキシ、置換もしくは非置換の芳香族複素環カルボニルオキシ、置換もしくは非置換の非芳香族複素環カルボニルオキシ、置換もしくは非置換の芳香族炭素環カルボニル、置換もしくは非置換の非芳香族炭素環カルボニル、置換もしくは非置換の芳香族複素環カルボニル、置換もしくは非置換の非芳香族複素環カルボニル、置換もしくは非置換の芳香族炭素環オキシカルボニル、置換もしくは非置換の非芳香族炭素環オキシカルボニル、置換もしくは非置換の芳香族複素環オキシカルボニル、置換もしくは非置換の非芳香族複素環オキシカルボニル、置換もしくは非置換の芳香族炭素環スルファニル、置換もしくは非置換の非芳香族炭素環スルファニル、置換もしくは非置換の芳香族複素環スルファニル、置換もしくは非置換の非芳香族複素環スルファニル、置換もしくは非置換の芳香族炭素環スルフィニル、置換もしくは非置換の非芳香族炭素環スルフィニル、置換もしくは非置換の芳香族複素環スルフィニル、置換もしくは非置換の非芳香族複素環スルフィニル、置換もしくは非置換の芳香族炭素環スルホニル、置換もしくは非置換の非芳香族炭素環スルホニル、置換もしくは非置換の芳香族複素環スルホニル、置換もしくは非置換の非芳香族複素環スルホニル、式：－Ｌ－Ｎ＝Ｓ（＝Ｏ）（－Ｒ^S1）－Ｒ^S2、式：－Ｌ－Ｓ（＝Ｏ）（＝Ｎ－Ｒ^N）－Ｒ^S1、式：－Ｎ＝Ｓ（＝Ｎ－Ｒ^N）（－Ｒ^S1）－Ｒ^S2、または式：－Ｓ（＝Ｎ－Ｒ^N）₂－Ｒ^S1で示される基であり、
ｎは、０～４の整数であり、
Ｂ¹、Ｂ²、Ｂ³、Ｂ⁴およびＢ⁵は、前記［３’］と同意義であり、
その他の記号は、前記［１’］と同意義である）
［５’］環Ｂが、以下のいずれかの式で示される、前記［１’］～［４’］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
式：

（式中、Ｒ⁶およびｎは、前記［４’］と同意義であり、
Ｂ¹、Ｂ²、Ｂ³、Ｂ⁴およびＢ⁵は、前記［３’］と同意義であり、
その他の記号は、前記［１’］と同意義である）
［６’］Ｒ⁶が、それぞれ独立して、ハロゲン、シアノ、ヒドロキシ、置換もしくは非置換のアミノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のスルファモイル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の非芳香族炭素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルである、前記［４’］または［５’］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［７’］環Ｃが、芳香族炭素環または芳香族複素環である、前記［１’］または［２’］記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［８’］Ｒ⁵が、それぞれ独立して、ハロゲン、シアノ、ヒドロキシ、置換もしくは非置換のアミノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のカルバモイル、置換もしくは非置換のスルファモイル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、置換もしくは非置換の非芳香族複素環式基、置換もしくは非置換の非芳香族炭素環オキシ、置換もしくは非置換の非芳香族複素環オキシ、置換もしくは非置換の非芳香族炭素環スルホニル、または置換もしくは非置換の非芳香族複素環スルホニルであり、
ｎが１～３である、前記［１’］、［２’］または［７’］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［９’］Ｒ^2bが、水素、または置換もしくは非置換のアルキルである、前記［１’］、［２’］、［７’］または［８’］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［１０’］Ｒ^4aが、以下に示される基である、前記［１’］～［９’］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。

（式中、
Ｌ¹は、単結合または置換もしくは非置換のアルキレンであり、
Ｌ²は、単結合、－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｏ－、－Ｏ－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｎ（Ｈ）－、－Ｎ（Ｈ）－Ｃ（＝Ｏ）－、－Ｃ（＝Ｏ）－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－、または－Ｎ（Ｈ）－Ｓ（＝Ｏ）₂－であり、
Ｌ³は、単結合または置換もしくは非置換のアルキレンであり、
Ｒ⁷は、水素、ハロゲン、ヒドロキシ、シアノ、置換もしくは非置換のアミノ、置換もしくは非置換のアルキル、置換もしくは非置換のアルキルオキシ、置換もしくは非置換のアルキルスルホニル、置換もしくは非置換のアルキルアミノスルホニル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、または置換もしくは非置換の非芳香族複素環式基である。
ただし、Ｌ¹、Ｌ²、およびＬ³が単結合の場合は、Ｒ⁷は、水素、またはヒドロキシではない）。
［１１’］Ｒ^4bが、置換もしくは非置換のアルキル、置換もしくは非置換の芳香族炭素環式基、置換もしくは非置換の非芳香族炭素環式基、置換もしくは非置換の芳香族複素環式基、または置換もしくは非置換の非芳香族複素環式基である、前記［１’］～［１０’］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［１２’］Ｒ^3aが、水素、ハロゲン、または置換もしくは非置換のアルキルであり、Ｒ^3bが、水素、ハロゲン、または置換もしくは非置換のアルキルである、前記［１’］～［１１’］のいずれかに記載の化合物、またはその製薬上許容される塩、を含有する医薬組成物。
［１３’］ＭＧＡＴ２阻害作用を有する、前記前記［１’］～［１２’］のいずれかに記載の医薬組成物。
［１４’］ＭＧＡＴ２の関与する疾患の治療または予防のために用いる、前記［１３’］記載の医薬組成物。
［１５’］肥満症、メタボリックシンドローム、高脂血症、高中性脂肪血症、高ＶＬＤＬ血症、高脂肪酸血症、糖尿病または動脈硬化症の治療または予防のために用いる、前記［１４’］記載の医薬組成物。 [1'] Equation (I'):

(During the ceremony,
Ring A is a benzene ring or a 5- or 6-membered aromatic heterocycle.
Z ¹ is C, or N,
Z ² is C, or N,
The dashed line represents the presence or absence of a bond, where Z ¹ is C and Z ² is C.
X is C (= O), C (= S), or SO ₂ .

R ¹ is hydrogen, hydroxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted. Substituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or non-substituted Substituted aromatic carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, substituted or unsubstituted non-aromatic heterocyclic carbonyls, substituted or unsubstituted aromatics Carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic A carbocyclic sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic sulfonyl, a substituted or unsubstituted aromatic heterocyclic sulfonyl, or a substituted or unsubstituted non-aromatic heterocyclic sulfonyl.
However, R ¹ is the formula:

Not;

R ^2a and R ^2b together with adjacent carbon atoms form ring B, forming a ring B.
Ring B is a substituted or unsubstituted non-aromatic carbocycle or a substituted or unsubstituted non-aromatic heterocycle.
However, when the ring A is a 5-membered aromatic heterocycle, R ^2a is expressed by the formula:

R ^2b may be hydrogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted alkylsulfonyl. May be,
Ring C is an aromatic carbocycle, an aromatic heterocycle, a non-aromatic heterocycle, or a non-aromatic carbocycle having 4 to 16 carbon atoms.
R ⁵ are independently halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted. Ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted. Alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted Alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted Alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups. Formula groups, substituted or unsubstituted aromatic carbocyclic oxys, substituted or unsubstituted non-aromatic carbocyclic oxys, substituted or unsubstituted aromatic heterocyclic oxys, substituted or unsubstituted non-aromatic heterocyclic oxys, substituted Alternatively, unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted. Alternatively, an unsubstituted or unsubstituted aromatic carbocyclic carbonyl, a substituted or unsubstituted non-aromatic carbocyclic carbonyl, a substituted or unsubstituted aromatic heterocyclic carbonyl, a substituted or unsubstituted non-aromatic heterocyclic carbonyl, a substituted or unsubstituted. Aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted Aromatic carbocyclic sulfanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or Unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic Group heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl , Substituted or unsubstituted non-aromatic heterocyclic sulfonyl, Formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN ) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (= ^N - ^RN ) ₂ -RS1.
n is an integer from 1 to 5;

R ^3a is hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted. Substituent non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic group oxy, substituted or Unsubstituted non-aromatic carbocyclic group oxy, substituted or unsubstituted aromatic heterocyclic group oxy, substituted or unsubstituted non-aromatic heterocyclic group oxy, substituted or unsubstituted aromatic carbocyclic group A sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic group sulfonyl, a substituted or unsubstituted aromatic heterocyclic group sulfonyl, or a substituted or unsubstituted non-aromatic heterocyclic group sulfonyl.
R ^3b is hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted. Substituent non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic group oxy, substituted or Unsubstituted non-aromatic carbocyclic group oxy, substituted or unsubstituted aromatic heterocyclic group oxy, substituted or unsubstituted non-aromatic heterocyclic group oxy, substituted or unsubstituted aromatic carbocyclic group A sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic group sulfonyl, a substituted or unsubstituted aromatic heterocyclic group sulfonyl, or a substituted or unsubstituted non-aromatic heterocyclic group sulfonyl, or with R ^3a . R ^3b may be combined with adjacent carbon atoms to form a substituted or unsubstituted non-aromatic carbon ring or a substituted or unsubstituted non-aromatic heterocycle;

R ^4a is the formula:

L ¹ is a single bond or substituted or unsubstituted alkylene,
L ² is a single bond, -C (= O)-, -C (= O) -O-, -OC (= O)-, -C (= O) -N (H)-, -N. (H) -C (= O)-, -C (= O) -N (H) -S (= O) _2- , -N (H) -S (= O) _2- , -S (= O) ) ₂ -N (H)-or-S (= O) ₂ -N (H) -C (= O)-
L ³ is a single bond or substituted or unsubstituted alkylene,
R ⁷ is a hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureido, Substituent or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, Substituent or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxy Carbonyl, substituted or unsubstituted alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, Substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, Substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted Aromatic Carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic Carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted Aromatic carbon ring carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbon Ring oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbon Ring sulfanyl, substituted or unsubstituted non-aromatic Carbocyclic sulfanyl, substituted or unsubstituted fragrance Group heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbon ring sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl. , Substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or non-substituted Substituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , formula: -LS (= O) (= ^N -RN) ^-RS1 , Formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or Formula: -S (= ^N - ^RN ) ₂ -RS1.
However, if L ¹ , L ² , and L ³ are single bonds, then R ⁷ is not hydrogen or hydroxy,
R ^4b is halogen, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted. Guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted. Alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or Unsubstituted alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted. Aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted. Aromatic carbon ring oxy, substituted or unsubstituted non-aromatic carbon ring oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbon Ring carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbon Ring carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, Substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfanyl, substituted Or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfa Nyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or Unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or the formula: -S (= ^N - ^RN ) ₂ -RS1.
R ^4c are independently halogen, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid. , Substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy. , Substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyl Oxycarbonyl, substituted or unsubstituted alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl , Substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group , Substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or non-substituted Substituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or non-substituted Substituted aromatic carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, substituted or unsubstituted non-aromatic heterocyclic carbonyls, substituted or unsubstituted aromatics Carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic Carocyclic sulfanyl, substituted or unsubstituted non-aromatic carousyl sulfanyl, substituted or unsubstituted. Fragrant heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbon ring sulfinyl, substituted or unsubstituted non-aromatic carbon ring sulfinyl, substituted or unsubstituted aromatic heterocycle Sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or Unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , formula: -LS (= O) (= ^N -RN) -R ^S1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (= ^N - ^RN ) ₂ -RS1.
However, R ^4a , R ^4b , and R ^4c are not benzyloxy, methyloxy and methylsulfanyl;
m is an integer from 0 to 3 and
L is independently single bond, alkylene, or C (= O), respectively.
R ^S1 and R ^S2 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted. An aromatic heterocyclic group, or a substituted or unsubstituted non-aromatic heterocyclic group, or
RS1 and ^RS2 bonded to the same sulfur atom may be combined with the sulfur atom to form a substituted or ^{unsubstituted} non-aromatic heterocycle;
^RNs are independently hydrogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aromatics, respectively. Group carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted fragrances. Group carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, or substituted or unsubstituted non-aromatic heterocyclic carbonyls)
Compounds indicated by,
(However, the following compounds are excluded

) Or a pharmaceutically acceptable salt thereof, a pharmaceutical composition.
[2'] Expression:

The part indicated by

(During the ceremony,
R ^4c'is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, Substituent or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted Alternatively, an unsubstituted non-aromatic carbocyclic carbonyl, a substituted or unsubstituted aromatic heterocyclic carbonyl, a substituted or unsubstituted non-aromatic heterocyclic carbonyl, a substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or non-substituted. Substituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, or substituted or unsubstituted. It is a non-aromatic heterocyclic sulfonyl and is
Each other symbol has the same meaning as the above [1'])
A pharmaceutical composition containing the compound according to the above [1'], or a pharmaceutically acceptable salt thereof, which is indicated by.
[3'] A pharmaceutical composition in which ring B contains the compound according to the above [1'] or [2'], or a pharmaceutically acceptable salt thereof, which is represented by any of the following formulas.
formula:

(During the ceremony,
B ¹ is CR ^11a R ^11b , NR ^11c , O, or S.
B ² is CR ^12a R ^12b , NR ^12c , O, or S.
B ³ is CR ^13a R ^13b , NR ^13c , O, or S.
B ⁴ is CR ^14a R ^14b , NR ^14c , O, or S, and B ⁵ is CR ^15a R ^15b , NR ^15c , O, or S.
R ^11a , R ^12a , R ^13a , R ^14a , and R ^15a are independently hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or non-substituted, respectively. Substituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted. Alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenyl Carbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenyl Sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocycles. Oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy , Substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or Unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or non-substituted Substituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocycles Rufanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or Unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (=) ^N -RN) ₂ - ^RS1 is a group represented by
R ^11b , R ^12b , R ^13b , R ^14b , and R ^15b are independently hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or non-substituted, respectively. Substituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted. Alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenyl Carbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenyl Sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocycles. Oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy , Substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or Unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or non-substituted Substituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocycles Rufanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or Unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-substituted Aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (=) ^N -RN) ₂ - ^RS1 is a group represented by
R ^11c , R ^12c , R ^13c , R ^14c , and R ^15c are independently hydrogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or Unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkenyl, substituted or unsubstituted. Alkoxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted. Alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted fragrance. Group carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatics. Group carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyl , Substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or Unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfanyl, substituted or non-substituted Substituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic Group Carbocyclic Sulfinyl, Substituted or unsubstituted Aromatic Heterocyclic Sulfinyl, Substituted or unsubstituted Non-Aromatic Heterocyclic Sulfinyl Finyl, substituted or unsubstituted aromatic carbocyclic sulfonyls, substituted or unsubstituted non-aromatic carbocyclic sulfonyls, substituted or unsubstituted aromatic heterocyclic sulfonyls, or substituted or unsubstituted non-aromatic heterocyclic sulfonyls. ,
Alternatively, R ^11a and R ^12a , R ^12a and R ^13a , R ^13a and R ^14a , and / or R ^14a and R ^15a , together with adjacent carbon atoms, are substituted or unsubstituted aromatic carbon rings, Substituted or unsubstituted non-aromatic carbocycles, substituted or unsubstituted aromatic heterocycles, or substituted or unsubstituted non-aromatic heterocycles may be formed.
And / or R ^11c and R ^12a , R ^11c and R ^12c , R ^12c and R ^11a , R ^12c and R ^13a , R ^12c and R ^13c , R ^13c and R ^12a , R ^13c and R ^14a , R ^13c and R ^14c , R ^14c and R ^13a , R ^14c and R ^15a , R ^14c and R ^15c , and / or R ^15c and R ^14a , together with adjacent atoms, are substituted or unsubstituted aromatic heterocycles or substitutions. Alternatively, an unsubstituted non-aromatic heterocycle may be formed.
And / or R ^11a and R ^13a , R ^11a and R ^13c , R ^11a and R ^14a , R ^11a and R ^14c , R ^11a and R ^15a , R ^11a and R ^15c , R ^11c and R ^13a , R ^11c and R ^13c , R ^11c and R ^14a , R ^11c and R ^14c , R ^11c and R ^15a , R ^11c and R ^15c , R ^12a and R ^14a , R ^12a and R ^14c , R ^12a and R ^15a , R ^12a and R ^15c , R ^12c and R ^14a , R ^12c and R ^14c , R ^12c and R ^15a , R ^12c and R ^15c , R ^13a and R ^15a , R ^13a and R ^15c , R ^13c and R ^15a , and / or R ^13c and R ^15c . May together form a C2-C4 crosslink that may intervene heteroatoms.
And / or R ^11b and R ^12b , R ^11b and R ^12c , R ^11c and R ^12b , R ^11c and R ^12c , R ^12b and R ^13b , R ^12b and R ^13c , R ^12c and R ^13b , R ^12c and R ^13c , R ^13b and R ^14b , R ^13b and R ^14c , R ^13c and R ^14b , R ^13c and R ^14c , R ^14b and R ^15b , R ^14b and R ^15c , R ^14c and R ^15b , and / or R ^14c . R ^15c may be combined to form a bond,
Dashed lines indicate the presence or absence of bonds,
Other symbols have the same meaning as the above [1'])
[4'] Ring B is a pharmaceutical composition containing the compound according to any one of the above [1'] to [3'] represented by any of the following formulas, or a pharmaceutically acceptable salt thereof. thing.
formula:

(During the ceremony,
Ring D is an aromatic carbocycle, a non-aromatic carbocycle, an aromatic heterocycle, or a non-aromatic heterocycle.
R ⁶ are independently halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted. Ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted. Alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted Alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted Alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups. Formula groups, substituted or unsubstituted aromatic carbocyclic oxys, substituted or unsubstituted non-aromatic carbocyclic oxys, substituted or unsubstituted aromatic heterocyclic oxys, substituted or unsubstituted non-aromatic heterocyclic oxys, substituted Alternatively, unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, substituted. Alternatively, an unsubstituted or unsubstituted aromatic carbocyclic carbonyl, a substituted or unsubstituted non-aromatic carbocyclic carbonyl, a substituted or unsubstituted aromatic heterocyclic carbonyl, a substituted or unsubstituted non-aromatic heterocyclic carbonyl, a substituted or unsubstituted. Aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted Aromatic carbocyclic sulfanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or Unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic Group heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl , Substituted or unsubstituted non-aromatic heterocyclic sulfonyl, Formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , Formula: -LS (= O) (= ^N -RN ) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (= ^N - ^RN ) ₂ -RS1.
n is an integer from 0 to 4,
B ¹ , B ² , B ³ , B ⁴ and B ⁵ have the same meaning as the above [3'].
Other symbols have the same meaning as the above [1'])
[5'] Ring B is a pharmaceutical composition containing the compound according to any one of the above [1'] to [4'] represented by any of the following formulas, or a pharmaceutically acceptable salt thereof. thing.
formula:

(In the formula, R ⁶ and n have the same meaning as the above [4'].
B ¹ , B ² , B ³ , B ⁴ and B ⁵ have the same meaning as the above [3'].
Other symbols have the same meaning as the above [1'])
[6'] R ⁶ are independently halogen, cyano, hydroxy, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted carbamoyl, substituted or Unsubstituted sulfamoyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic groups. Heterocyclic groups, substituted or unsubstituted non-aromatic carbocyclic oxys, substituted or unsubstituted non-aromatic heterocyclic oxys, substituted or unsubstituted non-aromatic carbocyclic sulfonyls, or substituted or unsubstituted non-aromatics. A pharmaceutical composition containing the compound according to the above [4'] or [5'], which is a heterocyclic sulfonyl, or a pharmaceutically acceptable salt thereof.
[7'] A pharmaceutical composition containing the compound according to the above [1'] or [2'], or a pharmaceutically acceptable salt thereof, wherein the ring C is an aromatic carbocycle or an aromatic heterocycle.
[8'] R ⁵ are independently halogen, cyano, hydroxy, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted carbamoyl, substituted or Unsubstituted sulfamoyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic groups. Heterocyclic groups, substituted or unsubstituted non-aromatic carbocyclic oxys, substituted or unsubstituted non-aromatic heterocyclic oxys, substituted or unsubstituted non-aromatic carbocyclic sulfonyls, or substituted or unsubstituted non-aromatics. It is a heterocyclic sulfonyl,
A pharmaceutical composition containing the compound according to any one of the above [1'], [2'] or [7'], or a pharmaceutically acceptable salt thereof, wherein n is 1 to 3.
[9'] The compound according to any one of the above [1'], [2'], [7'] or [8'], wherein R ^2b is hydrogen or a substituted or unsubstituted alkyl, or a compound thereof. A pharmaceutical composition containing a pharmaceutically acceptable salt.
[10'] R ^4a is a pharmaceutical composition containing the compound according to any one of the above [1'] to [9'], or a pharmaceutically acceptable salt thereof, which is a group shown below.

(During the ceremony,
L ¹ is a single bond or substituted or unsubstituted alkylene,
L ² is a single bond, -C (= O)-, -C (= O) -O-, -OC (= O)-, -C (= O) -N (H)-, -N. (H) -C (= O)-, -C (= O) -N (H) -S (= O) _2- , or -N (H) -S (= O) _2- , and
L ³ is a single bond or substituted or unsubstituted alkylene,
R ⁷ is hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkylaminosulfonyl. , Substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, or substituted or unsubstituted non-aromatic heterocyclic group. It is a group.
However, if L ¹ , L ² , and L ³ are single bonds, then R ⁷ is not hydrogen or hydroxy).
[11'] R ^4b is a substituted or unsubstituted alkyl, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-aromatic carbocyclic group, a substituted or unsubstituted aromatic heterocyclic group. A pharmaceutical composition containing the compound according to any one of the above [1'] to [10'], or a pharmaceutically acceptable salt thereof, which is a group or a substituted or unsubstituted non-aromatic heterocyclic group. thing.
[12'] R ^3a is a hydrogen, halogen, or substituted or unsubstituted alkyl, and R ^3b is a hydrogen, halogen, or substituted or unsubstituted alkyl, the above-mentioned [1'] to [11']. A pharmaceutical composition containing the compound according to any one of the above, or a pharmaceutically acceptable salt thereof.
[13'] The pharmaceutical composition according to any one of the above [1'] to [12'], which has an MGAT2 inhibitory effect.
[14'] The pharmaceutical composition according to the above [13'], which is used for treating or preventing a disease associated with MGAT2.
[15'] The above-mentioned [14'] used for the treatment or prevention of obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, hyperfatty acidemia, diabetes or arteriosclerosis. The pharmaceutical composition described.

The pharmaceutical composition of the present invention has an MGAT2 inhibitory action and is a preventive agent for obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, hyperfatty acidemia, diabetes or arteriosclerosis. And / or useful as a therapeutic agent.

It is a result of measurement according to Test Example 6 using compound I-23.

The meaning of each term used in the present specification will be described below. Unless otherwise specified, each term is used interchangeably when used alone or in combination with other terms.
The term "consisting of" means having only constituent requirements.
The term "contains" is not limited to the constituents and means does not exclude elements not described.

"Halogen" includes a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. Fluorine atoms and chlorine atoms are particularly preferable.

The "alkyl" includes a linear or branched hydrocarbon group having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, still more preferably 1 to 4 carbon atoms. do. For example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl. , Isooctyl, n-nonyl, n-decyl and the like.
Preferred embodiments of "alkyl" include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and n-pentyl. More preferred embodiments include methyl, ethyl, n-propyl, isopropyl and tert-butyl.

The "alkenyl" has 1 or more double bonds at arbitrary positions and has 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, and further preferably 2 to 4 carbon atoms. Includes linear or branched hydrocarbon groups of. For example, vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetra. And so on.
Preferred embodiments of the "alkenyl" include vinyl, allyl, propenyl, isopropenyl, butenyl.

The "alkynyl" has 1 or more triple bonds at arbitrary positions and has 2 to 10 carbon atoms, preferably 2 to 8 carbon atoms, more preferably 2 to 6 carbon atoms, and further preferably 2 to 4 carbon atoms. Includes linear or branched hydrocarbon groups. Further, it may have a double bond at an arbitrary position. For example, it includes ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, noninyl, decynyl and the like.
Preferred embodiments of "alkynyl" include ethynyl, propynyl, butynyl, pentynyl.

The “alkylene” is a linear or branched divalent hydrocarbon having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and further preferably 1 to 4 carbon atoms. Includes groups. For example, methylene, ethylene, propylene, tetramethylene, pentamethylene, hexamethylene and the like can be mentioned.

The "aromatic carbocyclic group" means a cyclic aromatic hydrocarbon group having a single ring or two or more rings. For example, phenyl, naphthyl, anthryl, phenanthryl and the like can be mentioned.
A preferred embodiment of the "aromatic carbocyclic group" is phenyl.

単環の非芳香族炭素環式基としては、炭素数３～１６が好ましく、より好ましくは炭素数３～１２、さらに好ましくは炭素数４～８である。例えば、シクロプロピル、シクロブチル、シクロペンチル、シクロヘキシル、シクロヘプチル、シクロオクチル、シクロノニル、シクロデシル、シクロプロペニル、シクロブテニル、シクロペンテニル、シクロヘキセニル、シクロヘプテニル、シクロヘキサジエニル等が挙げられる。
２環以上の非芳香族炭素環式基としては、炭素数８～２０が好ましく、より好ましくは炭素数８～１６である。例えば、インダニル、インデニル、アセナフチル、テトラヒドロナフチル、フルオレニル等が挙げられる。 The "non-aromatic carbocyclic group" means a cyclic saturated hydrocarbon group or a cyclic non-aromatic unsaturated hydrocarbon group having a single ring or two or more rings. The "non-aromatic carbocyclic group" having two or more rings also includes a monocyclic or two or more non-aromatic carbocyclic groups fused with the ring in the above "aromatic carbocyclic group".
Furthermore, the "non-aromatic carbocyclic group" also includes a group that is crosslinked as follows, or a group that forms a spiro ring.

The monocyclic non-aromatic carbocyclic group preferably has 3 to 16 carbon atoms, more preferably 3 to 12 carbon atoms, and further preferably 4 to 8 carbon atoms. For example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclopropenium, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclohexadienyl and the like can be mentioned.
The non-aromatic carbocyclic group having two or more rings preferably has 8 to 20 carbon atoms, and more preferably 8 to 16 carbon atoms. For example, indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, fluorenyl and the like can be mentioned.

単環の非芳香族炭素環としては、炭素数３～１６が好ましく、より好ましくは炭素数３～１２、さらに好ましくは炭素数３～８である。例えば、シクロプロパン、シクロブタン、シクロペンタン、シクロヘキサン、シクロヘプタン、シクロオクタン、シクロノナン、シクロデカン、シクロプロペン、シクロブテン、シクロペンテン、シクロヘキセン、シクロヘプテン、シクロヘキサジエン等が挙げられる。
２環以上の非芳香族炭素環としては、炭素数８～２０が好ましく、より好ましくは炭素数８～１６である。例えば、インダン、インデン、アセナフチレン、テトラヒドロナフタレン、フルオレン等が挙げられる。 The "aromatic carbocyclic ring" includes a single ring or two or more cyclic aromatic hydrocarbons. For example, a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring and the like can be mentioned.
As one embodiment of the "aromatic carbocycle", a benzene ring and a naphthalene ring can be mentioned. Another embodiment is a benzene ring.
The "non-aromatic carbon ring" includes a cyclic saturated hydrocarbon or a cyclic non-aromatic unsaturated hydrocarbon having a single ring or two or more rings. The "non-aromatic carbon ring" having two or more rings also includes a monocyclic ring or a non-aromatic carbon ring having two or more rings in which the ring in the above "aromatic carbon ring" is condensed.
Furthermore, the "non-aromatic carbon ring" also includes a ring that is crosslinked as follows, or a ring that forms a spiro ring.

The monocyclic non-aromatic carbon ring preferably has 3 to 16 carbon atoms, more preferably 3 to 12 carbon atoms, and further preferably 3 to 8 carbon atoms. For example, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclononane, cyclodecane, cyclopropene, cyclobutene, cyclopentene, cyclohexene, cycloheptene, cyclohexadiene and the like can be mentioned.
The non-aromatic carbon ring having two or more rings preferably has 8 to 20 carbon atoms, and more preferably 8 to 16 carbon atoms. For example, indane, indene, acenaphthylene, tetrahydronaphthylene, fluorene and the like can be mentioned.

"Aromatic heterocyclic group" means a monocyclic or two or more aromatic cyclic groups having one or more identical or different heteroatoms arbitrarily selected from O, S and N in the ring. do. The aromatic heterocyclic group having two or more rings includes a monocyclic or an aromatic heterocyclic group having two or more rings fused with the ring in the above-mentioned "aromatic carbocyclic group".
The monocyclic aromatic heterocyclic group is preferably 5 to 8 members, more preferably 5 or 6 members. Examples thereof include pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridadinyl, pyrimidinyl, pyrazinyl, triazolyl, triazinyl, tetrazolyl, frill, thienyl, isooxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl and the like.
The two-ring aromatic heterocyclic group is preferably 8 to 10-membered, more preferably 9- or 10-membered. For example, indolyl, isoindrill, indazolyl, indolidinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyldinyl, quinoxalinyl, prynyl, pteridinyl, benzimidazolyl, benzisooxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiolyl. Lil, benzothiazolyl, benzothiasiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazolipyridyl, triazolopyridyl, imidazoliazolyl, pyrazinopyridazinyl, oxazolopyridyl, thiazolopyridyl, etc. Can be mentioned.
Examples of the aromatic heterocyclic group having three or more rings include carbazolyl, acridinyl, xanthenyl, phenothiazine, phenoxatiinyl, phenoxadinyl, dibenzofuryl and the like.

単環の非芳香族複素環式基としては、３～８員が好ましく、より好ましくは５員または６員である。例えば、ジオキサニル、チイラニル、オキシラニル、オキセタニル、オキサチオラニル、アゼチジニル、チアニル、チアゾリジニル、ピロリジニル、ピロリニル、イミダゾリジニル、イミダゾリニル、ピラゾリジニル、ピラゾリニル、ピペリジル、ピペラジニル、モルホリニル、モルホリノ、チオモルホリニル、チオモルホリノ、ジヒドロピリジル、テトラヒドロピリジル、テトラヒドロフリル、テトラヒドロピラニル、ジヒドロチアゾリル、テトラヒドロチアゾリル、テトラヒドロイソチアゾリル、ジヒドロオキサジニル、ヘキサヒドロアゼピニル、テトラヒドロジアゼピニル、テトラヒドロピリダジニル、ヘキサヒドロピリミジニル、ジオキソラニル、ジオキサジニル、アジリジニル、ジオキソリニル、オキセパニル、チオラニル、チイニル、チアジニル等が挙げられる。
２環以上の非芳香族複素環式基としては、８～２０員が好ましく、より好ましくは８～１０員である。例えば、インドリニル、イソインドリニル、クロマニル、イソクロマニル等が挙げられる。 A "non-aromatic heterocyclic group" is a monocyclic or two or more cyclic non-aromatic cyclic group having one or more identical or different heteroatoms arbitrarily selected from O, S and N in the ring. Means the group. The non-aromatic heterocyclic group having two or more rings is a monocyclic or non-aromatic heterocyclic group having two or more rings, and the above-mentioned "aromatic carbocyclic group", "non-aromatic carbocyclic group", and the above-mentioned "aromatic carbocyclic group". / Or a fused ring of each of the "aromatic heterocyclic groups", and a single ring or two or more non-aromatic carbocyclic groups fused with the ring of the above "aromatic heterocyclic group". Also includes those that have been used.
Furthermore, the "non-aromatic heterocyclic group" also includes a group that is crosslinked as follows, or a group that forms a spiro ring.

The monocyclic non-aromatic heterocyclic group is preferably 3 to 8 members, more preferably 5 or 6 members. For example, dioxanyl, tiylanyl, oxylanyl, oxetanyl, oxathiolanyl, azetidinyl, thianyl, thiazolidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazoridinyl, pyrazolinyl, piperidyl, piperazinyl, pyrazolinyl, piperidyl, piperazinyl, morpholinyl, morpholinohydro Frills, tetrahydropyranyl, dihydrothiazolyl, tetrahydrothiazolyl, tetrahydroisothiazolyl, dihydrooxadinyl, hexahydroazepinyl, tetrahydrodiazepinyl, tetrahydropyranidazinyl, hexahydropyrimidinyl, dioxolanyl, dioxadinyl , Aziridinyl, dioxolinyl, oxepanyl, thiolanyl, tiinyl, thiazinyl and the like.
The non-aromatic heterocyclic group having two or more rings is preferably 8 to 20 members, more preferably 8 to 10 members. For example, indolinyl, isoindrinyl, chromanyl, isochromanyl and the like can be mentioned.

単環の非芳香族複素環としては、３～８員が好ましく、より好ましくは５員または６員である。例えば、ジオキサン、チイラン、オキシラン、オキセタン、オキサチオラン、アゼチジン、チアン、チアゾリジン、ピロリジン、ピロリン、イミダゾリジン、イミダゾリン、ピラゾリジン、ピラゾリン、ピペリジン、ピペラジン、モルホリン、チオモルホリン、ジヒドロピリジン、テトラヒドロピリジン、テトラヒドロフラン、テトラヒドロピラン、ジヒドロチアゾール、テトラヒドロチアゾール、テトラヒドロイソチアゾール、ジヒドロオキサジン、ヘキサヒドロアゼピン、テトラヒドロジアゼピン、テトラヒドロピリダジン、ヘキサヒドロピリミジン、ジオキソラン、ジオキサジン、アジリジン、ジオキソール、オキセパン、チオラン、チイン、チアジン等が挙げられる。
２環以上の非芳香族複素環としては、８～２０員が好ましく、８～１０員である。例えば、インドリン、イソインドリン、クロマン、イソクロマン等が挙げられる。 The "aromatic heterocycle" includes a monocyclic or two or more aromatic rings having one or more identical or different heteroatoms arbitrarily selected from O, S and N in the ring.
The "aromatic heterocycle" having two or more rings also includes a monocycle or an aromatic heterocycle having two or more rings in which the ring in the above "aromatic carbon ring" is condensed.
The monocyclic aromatic heterocycle is preferably 5 to 8 members, more preferably 5 or 6 members. For example, pyrrole, imidazole, pyrazole, pyridine, pyridazine, pyrimidine, pyrazine, triazole, triazine, tetrazole, furan, thiophene, isoxazole, oxazole, oxadiazole, isothiazole, thiazole, thiadiazole and the like can be mentioned.
The two-ring aromatic heterocycle is preferably 8 to 10 members, more preferably 9 or 10 members. For example, indol, isoindole, indazole, indridin, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, naphthylidine, quinoxalin, purine, pteridine, benzimidazole, benzisoxazole, benzoxazole, benzoxadiazole, benzisothiazole, benzo. Examples thereof include thiazole, benzothiaziazole, benzofuran, isobenzofuran, benzothiophene, benzotriazole, imidazolepyridine, triazolopyridine, imidazolethiazole, pyrazinopyridazine, oxazolopyridine, thiazolopyridine and the like.
The aromatic heterocycle having 3 or more rings is preferably 11 to 26 members, more preferably 13 or 14 members. For example, carbazole, acridine, xanthene, phenothiazine, phenoxazine, phenoxazine, dibenzofuran and the like can be mentioned.
A "non-aromatic heterocycle" is a monocyclic or two or more cyclic non-aromatic rings having one or more identical or different heteroatoms arbitrarily selected from oxygen, sulfur and nitrogen atoms in the ring. Including.
The "non-aromatic heterocycle" having two or more rings is a single ring or a non-aromatic heterocycle having two or more rings, and the above-mentioned "aromatic carbocycle", "non-aromatic carbocycle", and / or "aromatic heterocycle". It also includes those in which each ring in the "ring" is condensed.
Furthermore, the "non-aromatic heterocycle" also includes a ring that is crosslinked as follows, or a ring that forms a spiro ring.

The monocyclic non-aromatic heterocycle is preferably 3 to 8 members, more preferably 5 or 6 members. For example, dioxane, thiirane, oxylan, oxetane, oxathiorane, azetidine, thiane, thiazolidine, pyrrolidine, pyrrolin, imidazolidine, imidazoline, pyrazolidine, pyrazoline, piperidine, piperazine, morpholine, thiomorpholin, dihydropyridine, tetrahydropyran, tetrahydrofuran, tetrahydropyran, Examples thereof include dihydrothiazole, tetrahydrothiazole, tetrahydroisothiazole, dihydrooxazine, hexahydroazepine, tetrahydrodiazepine, tetrahydropyrandazine, hexahydropyranmidin, dioxoran, dioxazine, aziridine, dioxol, oxetane, thiolan, thiane, thiazine and the like.
The non-aromatic heterocycle having two or more rings is preferably 8 to 20 members, preferably 8 to 10 members. For example, indoline, isoindoline, chroman, isochroman and the like can be mentioned.

"Substituted carbamoyl", "substituted thiocarbamoyl", "substituted amidino", "substituted amino", "substituted ureido", "substituted guanidino", "substituted sulfamoyl", "substituted alkyl", "substituted alkenyl", "substituted alkynyl" , "Substituted alkylene", "Substituted alkyloxy", "Substituted alkenyloxy", "Substituted alkylcarbonyloxy", "Substituted alkenylcarbonyloxy", "Substituted alkylcarbonyl", "Substituted alkenylcarbonyl", "Substituted alkyloxycarbonyl" , "Substituted Alkenyl Oxycarbonyl", "Substituted Alkyl Sulfanyl", "Substituted Alkyl Sulfanyl", "Substituted Alkyl Sulfinyl", "Substituted Alkenyl Sulfinyl", "Substituted Alkylsulfonyl", and as substituents for "Substituted Alkylsulfonyl" The following substituents are mentioned. A carbon atom or a nitrogen atom at an arbitrary position may be bonded to one or more groups selected from the following substituents.
Substituents: Halogen, Hydroxy, Cyano, Formyl, Formyloxy, Thioformyl, Carboxy, Thiocarboxy, Dithiocarboxy, Carbamoyl, Thiocarbamoyl, Amidino, Amino, Hydroxyamino, Hydroxyimino, Azido, Hydradino, Ureid, Guanidino, Pentafluorothio , Thiol, sulfino, sulfo, sulfamoyl, trialkylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkenyl, haloalkynyl, alkyloxy, alkenyloxy, alkynyloxy, haloalkyloxy, haloalkyloxyalkyl, alkylcarbonyloxy, alkenylcarbonyloxy , Alkinylcarbonyloxy, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, alkyloxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylsulfanyl, alkenylsulfanyl, alkynylsulfanyl, alkylsulfinyl, alkenylsulfinyl, alkynylsulfinyl, alkylsulfonyl, alkenylsulfonyl, Alkinylsulfonyl, Monoalkylaminosulfonyl, Monoalkenylaminosulfonyl, Monoalkynylaminosulfonyl, Dialkylaminosulfonyl, Dialkenylaminosulfonyl, Dialkynylaminosulfonyl, Monoalkylamino, Monoalkenylamino, Monoalkynylamino, Dialkylamino, Dialkenylamino , Dialkynylamino, Monoalkylcarbonylamino, Monoalkenylcarbonylamino, Monoalkynylcarbonylamino, Dialkylcarbonylamino, Dialkenylcarbonylamino, Dialkynylcarbonylamino, Monoalkyloxycarbonylamino, Monoalkenyloxycarbonylamino, Monoalkynyloxycarbonyl Amino, Dialkyloxycarbonylamino, Dialkenyloxycarbonylamino, Dialkynyloxycarbonylamino, Monoalkylsulfonylamino, Monoalkenylsulfonylamino, Monoalkynylsulfonylamino, Dialkylsulfonylamino, Dialkenylsulfonylamino, Dialkynylsulfonylamino, Monoalkyl Carbamoyl, monoalkenylcarbamoyl, monoalkynylcarbamoyl, dialkylcarbamoyl, dialkenylcarbamoyl, dialkynylcarbamoyl, monoa Lucyloxycarbamoyl, monoalkenyloxycarbamoyl, monoalkynyloxycarbamoyl, dialkyloxycarbamoyl, dialkenyloxycarbamoyl, dialkynyloxycarbamoyl, monoalkylcarbonylcarbamoyl, monoalkenylcarbonylcarbamoyl, monoalkynylcarbonylcarbamoyl, monoalkyloxycarbonylcarbamoyl, mono Alkenyloxycarbonylcarbamoyl, monoalkynyloxycarbonylcarbamoyl, monoalkylsulfonylcarbamoyl, monoalkenylsulfonylcarbamoyl, monoalkynylsulfonylcarbamoyl, monoalkylsulfamoyl, monoalkenylsulfamoyl, monoalkynylsulfamoyl, dialkylsulfamoyl, di. Alkenyl Sulfamoyl, Dialkynyl Sulfamoyl, Monoalkyloxy Sulfamoyl, Monoalkenyloxysulfamoyl, Monoalkynyloxysulfamoyl, Dialkyloxysulfamoyl, Dialkenyloxysulfamoyl, Dialkynyloxysulfa Moyl, monoalkylcarbonylsulfamoyl, monoalkenylcarbonylsulfamoyl, monoalkynylcarbonylsulfamoyl, monoalkyloxycarbonylsulfamoyl, monoalkenyloxycarbonylsulfamoyl, monoalkynyloxycarbonylsulfamoyl, monoalkylsulfonyl Sulfamoyl, monoalkenylsulfonylsulfamoyl, monoalkynylsulfonylsulfamoyl, aromatic carbocyclic group optionally substituted with substituent group A, non-aromatic carbon ring optionally substituted with substituent group A A formula group, an aromatic heterocyclic group which may be substituted with a substituent group A, a non-aromatic heterocyclic group which may be substituted with a substituent group A, and an aromatic group which may be substituted with a substituent group A. Carbocyclic oxy, non-aromatic carbocyclic oxy which may be substituted with substituent group A, aromatic heterocyclic oxy which may be substituted with substituent group A, non-aromatic which may be substituted with substituent group A. Heterocyclic oxy, aromatic carbocyclic carbonyloxy which may be substituted with substituent group A, non-aromatic carbocyclic carbonyloxy which may be substituted with substituent group A, fragrance which may be substituted with substituent group A. Group heterocyclic carbonyloxy, non-aromatic heterocyclic carbonyloxy which may be substituted with substituent group A, aromatic carbocyclic carbonyl which may be substituted with substituent group A, may be substituted with substituent group A. Non-aromatic charcoal Elementary ring carbonyl, aromatic heterocyclic carbonyl optionally substituted with substituent group A, non-aromatic heterocyclic carbonyl optionally substituted with substituent group A, aromatic carbon optionally substituted with substituent group A Ring oxycarbonyl, non-aromatic carbocyclic oxycarbonyl which may be substituted with substituent group A, aromatic heterocyclic oxycarbonyl which may be substituted with substituent group A, non-aromatic which may be substituted with substituent group A. Aromatic heterocyclic oxycarbonyl, aromatic carbocyclic sulfanyl which may be substituted with substituent group A, non-aromatic carbocyclic sulfanyl which may be substituted with substituent group A, may be substituted with substituent group A. Aromatic heterocyclic sulfanyl, non-aromatic heterocyclic sulfanyl which may be substituted with substituent group A, aromatic carbocyclic sulfinyl which may be substituted with substituent group A, non-optional which may be substituted with substituent group A. Aromatic carbocyclic sulfinyl, aromatic heterocyclic sulfinyl which may be substituted with substituent group A, non-aromatic heterocyclic sulfinyl which may be substituted with substituent group A, aromatic which may be substituted with substituent group A. Group carbocyclic sulfonyl, non-aromatic carbocyclic sulfonyl which may be substituted with substituent group A, aromatic heterocyclic sulfonyl which may be substituted with substituent group A, non-aromatic which may be substituted with substituent group A. Group heterocyclic sulfonyl, aromatic carbocyclic alkyl optionally substituted with substituent group A, non-aromatic carbocyclic alkyl optionally substituted with substituent group A, aromatic optionally substituted with substituent group A Heterocyclic alkyl, non-aromatic heterocyclic alkyl which may be substituted with substituent group A, aromatic carbocyclic alkyloxy which may be substituted with substituent group A, non-aromatic which may be substituted with substituent group A. Group carbocyclic alkyloxy, aromatic heterocyclic alkyloxy which may be substituted with substituent group A, non-aromatic heterocyclic alkyloxy which may be substituted with substituent group A, even when substituted with substituent group A Good aromatic carbocyclic alkylcarbonyl, non-aromatic carbocyclic alkylcarbonyl optionally substituted with substituent group A, aromatic heterocyclic alkylcarbonyl optionally substituted with substituent group A, substituted with substituent group A May be non-aromatic heterocyclic alkylcarbonyl, may be substituted with substituent group A aromatic carbocyclic alkyloxycarbonyl, non-aromatic carbocyclic alkyloxycarbonyl, may be substituted with substituent group A. Heterocyclic alkyloxycarbonyl, non-aromatic heterocyclic alkyloxycarbonyl optionally substituted with substituent group A, aromatic carbocyclic alkylsulfanyl optionally substituted with substituent group A, substituent group A Non-aromatic carbocyclic alkyl sulfanyl which may be substituted, aromatic heterocyclic alkyl sulfanyl which may be substituted with substituent group A, non-aromatic heterocyclic alkyl sulfanyl which may be substituted with substituent group A, substituent. Aromatic carbon ring alkylsulfinyl optionally substituted with group A, non-aromatic carbon ring alkylsulfinyl optionally substituted with substituent group A, aromatic heterocyclic alkylsulfinyl optionally substituted with substituent group A, Non-aromatic heterocyclic alkylsulfinyl which may be substituted with substituent group A, aromatic carbocyclic alkylsulfonyls which may be substituted with substituent group A, non-aromatic carbon ring which may be substituted with substituent group A. Alkylsulfonyl, aromatic heterocyclic alkylsulfonyls optionally substituted with substituent group A, non-aromatic heterocyclic alkylsulfonyls optionally substituted with substituent group A, aromatics optionally substituted with substituent group A Carbocyclic alkylamino, non-aromatic carbocyclic alkylamino which may be substituted with substituent group A, aromatic heterocyclic alkylamino which may be substituted with substituent group A, may be substituted with substituent group A. Non-aromatic heterocyclic alkylamino, aromatic carbocyclic alkylcarbonylamino optionally substituted with substituent group A, non-aromatic carbocyclic alkylcarbonylamino optionally substituted with substituent group A, substituent group A Fragrant aromatic heterocyclic alkylcarbonylamino which may be substituted, non-aromatic heterocyclic alkylcarbonylamino which may be substituted with substituent group A, aromatic carbocyclic alkyloxycarbonylamino which may be substituted with substituent group A. , Non-aromatic carbocyclic alkyloxycarbonylamino which may be substituted with substituent group A, aromatic heterocyclic alkyloxycarbonylamino which may be substituted with substituent group A, may be substituted with substituent group A. Non-aromatic heterocyclic alkyloxycarbonylamino, aromatic carbocyclic alkylsulfonylamino which may be substituted with substituent group A, non-aromatic carbocyclic alkylsulfonylamino which may be substituted with substituent group A, substituent group Aromatic heterocyclic alkylsulfonylamino which may be substituted with A, non-aromatic heterocyclic alkylsulfonylamino which may be substituted with substituent group A, aromatic carbocyclic oxyalkyl which may be substituted with substituent group A. Amino, a non-aromatic carbocyclic oxyalkylamino which may be substituted with a substituent group A, an aromatic heterocyclic oxyalkylamino which may be substituted with a substituent group A, and a substituent group A may be substituted. Non-aromatic heterocyclic oxyalkylamino.
"May be substituted with a substituent group A" means that a carbon atom, a nitrogen atom or a sulfur atom at an arbitrary position may be bonded to one or more groups selected from the substituent group A.
Substituent group A: oxo, halogen, hydroxy, alkyl, haloalkyl, hydroxyalkyl, alkyloxy, haloalkyloxy, alkyloxycarbonylalkyl, monoalkylamino, dialkylamino, aromatic carbocyclic group, aromatic heterocyclic group, And aromatic carbocyclic oxy.
The same applies to the following, "may be substituted with the substituent group B".
Substituents B: Halogen, alkyl, and haloalkyl.

"Substituted non-aromatic carbocycle", "substituted non-aromatic heterocycle", "substituted aromatic carbocyclic group", "substituted non-aromatic carbocyclic group", "substituted aromatic heterocyclic group", " Substituted non-aromatic heterocyclic groups ”,“ substituted aromatic carbocyclic oxys ”,“ substituted non-aromatic carbocyclic oxys ”,“ substituted aromatic heterocyclic oxys ”,“ substituted non-aromatic heterocyclic oxys ”,“ substituted "Aromatic Carbocyclic carbonyloxy", "Substituted non-aromatic carbocyclic carbonyloxy", "Substituted aromatic heterocyclic carbonyloxy", "Substituted non-aromatic heterocyclic carbonyloxy", "Substituted aromatic carbocyclic carbonyl", " Substituted non-aromatic carbocyclic carbonyl ”,“ Substituted aromatic heterocyclic carbonyl ”,“ Substituted non-aromatic heterocyclic carbonyl ”,“ Substituted aromatic carbocyclic oxycarbonyl ”,“ Substituted non-aromatic carbocyclic oxycarbonyl ”,“ Substituted Aromatic Heterocyclic Oxycarbonyl "," Substituted Non-Aromatic Heterocyclic Oxycarbonyl "," Substituted Aromatic Carbocyclic Sulfanyl "," Substituted Non-Aromatic Carbocyclic Sulfanyl "," Substituted Aromatic Heterocyclic Sulfanyl "," Substituted " Non-Aromatic Heterocyclic Sulfanyl, "Substituted Aromatic Carbocyclic Sulfinyl", "Substituted Non-Aromatic Carbocyclic Sulfinyl", "Substituted Aromatic Heterocyclic Sulfinyl", "Substituted Non-Aromatic Heterocyclic Sulfinyl", "Substituted Aromatic""Carbon Ring sulfonyl", "Substituted Non-Aromatic Carbocyclic sulfonyl", "Substituted Aromatic Heterocyclic sulfonyl", and "Substituted Non-Aromatic Heterocyclic sulfonyl""AromaticCarbocycle","Non-AromaticCarbocycle", Examples of the substituents on the rings of the "aromatic heterocycle" and the "non-aromatic heterocycle" include the following substituents. An atom at an arbitrary position on the ring may be bonded to one or more groups selected from the following substituents.
Substituents: oxo, halogen, hydroxy, cyano, formyl, formyloxy, thioformyl, carboxy, thiocarboxy, dithiocarboxy, carbamoyl, thiocarbamoyl, amidino, amino, hydroxyamino, imino, hydroxyimino, azide, hydrazino, ureido, guanidino , Pentafluorothio, thiol, sulfino, sulfo, sulfamoyl, trialkylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkenyloxy, alkynyloxy, haloalkyloxy, haloalkenyloxy, haloalkynyloxy, haloalkyloxyalkyloxy, Hydroxyalkyl, Alkylcarbonyloxy, Alkenylcarbonyloxy, Alkinylcarbonyloxy, Alkylcarbonyl, Alkenylcarbonyl, Alkinylcarbonyl, Alkyloxycarbonyl, Alkenyloxycarbonyl, Alkinyloxycarbonyl, Alkyl Sulfanyl, Alkenyl Sulfanyl, Alkinyl Sulfanyl, Alkyl Sulfinyl, Alkenyl Sulfinyl , Alkinyl sulfinyl, alkyl sulfonyl, alkenyl sulfonyl, alkynyl sulfonyl, monoalkyl amino sulfonyl, monoalkenyl amino sulfonyl, monoalkynyl amino sulfonyl, dialkyl amino sulfonyl, dialkenyl amino sulfonyl, dialkynyl amino sulfonyl, monoalkyl amino, monoalkenyl amino, Monoalkynylamino, Monohaloalkylamino, Dialkylamino, Dialkenylamino, Dialkynylamino, Monoalkylcarbonylamino, Monoalkenylcarbonylamino, Monoalkynylcarbonylamino, Monohaloalkylcarbonylamino, Dialkylcarbonylamino, Dialkenylcarbonylamino, Dialkynyl Carbonylamino, monoalkyloxycarbonylamino, monoalkenyloxycarbonylamino, monoalkynyloxycarbonylamino, dialkyloxycarbonylamino, dialkenyloxycarbonylamino, dialkynyloxycarbonylamino, monoalkylsulfonylamino, monoalkenylsulfonylamino, monoalkynyl Sulfonylamino, dialkylsulfonylamino, dialkenylsulfonylamino, dialkynylsulfonylamino, alkylimino, alkenylimino, alkynylimino, Alkyloxyimino, Alkenyloxyimino, Alkinyloxyimino, Monoalkylcarbamoyl, Monoalkenylcarbamoyl, Monoalkynylcarbamoyl, Dialkylcarbamoyl, Dialkenylcarbamoyl, Dialkynylcarbamoyl, Monoalkyloxycarbamoyl, Monoalkenyloxycarbamoyl, Monoalkynyloxycarbamoyl, Dialkyloxycarbamoyl, dialkenyloxycarbamoyl, dialkynyloxycarbamoyl, monoalkylcarbonylcarbamoyl, monoalkenylcarbonylcarbamoyl, monoalkynylcarbonylcarbamoyl, monoalkyloxycarbonylcarbamoyl, monoalkenyloxycarbonylcarbamoyl, monoalkynyloxycarbonylcarbamoyl, monoalkylsulfonyl Carbamoyl, monoalkenylsulfonylcarbamoyl, monoalkynylsulfonylcarbamoyl, monoalkylsulfamoyl, monoalkenyl sulfamoyl, monoalkynyl sulfamoyl, dialkylsulfamoyl, dialkenylsulfamoyl, dialkynylsulfamoyl, monoalkyloxy Sulfamoyl, monoalkenyloxysulfamoyl, monoalkynyloxysulfamoyl, dialkyloxysulfamoyl, dialkenyloxysulfamoyl, dialkynyloxysulfamoyl, monoalkylcarbonylsulfamoyl, monoalkenylcarbonylsulfa Moyl, monoalkynylcarbonylsulfamoyl, monoalkyloxycarbonylsulfamoyl, monoalkenyloxycarbonylsulfamoyl, monoalkynyloxycarbonylsulfamoyl, monoalkylsulfonylsulfamoyl, monoalkenylsulfonylsulfamoyl, monoalkynylsulfonyl Sulfamoyl, aromatic carbocyclic groups optionally substituted with substituent group A, non-aromatic carbocyclic groups optionally substituted with substituent group A, aromatics optionally substituted with substituent group A It may be substituted with a group heterocyclic group, a non-aromatic heterocyclic group which may be substituted with a substituent group A, an aromatic carbocyclic oxy which may be substituted with a substituent group A, or a substituent group A. Non-aromatic carbocyclic oxy, aromatic heterocyclic oxy which may be substituted with substituent group A, non-aromatic heterocyclic oxy which may be substituted with substituent group A, may be substituted with substituent group A. Aromatic carbocyclic carbonyloxy, non-aromatic which may be substituted with substituent group A Group Carbocyclic carbonyloxy, aromatic heterocyclic carbonyloxy which may be substituted with substituent group A, non-aromatic heterocyclic carbonyloxy which may be substituted with substituent group A, even when substituted with substituent group A Good aromatic carbocyclic carbonyl, non-aromatic carbocyclic carbonyl may be substituted with substituent group A, aromatic heterocyclic carbonyl may be substituted with substituent group A, may be substituted with substituent group A. Non-aromatic heterocyclic carbonyl, aromatic carbocyclic oxycarbonyl optionally substituted with substituent group A, non-aromatic carbocyclic oxycarbonyl optionally substituted with substituent group A, substituted with substituent group A May be aromatic heterocyclic oxycarbonyl, non-aromatic heterocyclic oxycarbonyl which may be substituted with substituent group A, aromatic carbocyclic sulfanyl which may be substituted with substituent group A, substituted with substituent group A. May be non-aromatic carbocyclic sulfanyl, optionally substituted with substituent group A aromatic heterocyclic sulfanyl, optionally substituted with substituent group A non-aromatic heterocyclic sulfanyl, substituted with substituent group A May be aromatic carbocyclic sulfinyl, may be substituted with substituent group A, may be substituted with non-aromatic carbocyclic ring sulfinyl, may be substituted with substituent group A, optionally substituted with aromatic heterocyclic sulfinyl, substituted with substituent group A. May be non-aromatic heterocyclic sulfinyl, aromatic carbocyclic sulfonyl which may be substituted with substituent group A, non-aromatic carbocyclic sulfonyl which may be substituted with substituent group A, substituted with substituent group A. May be aromatic heterocyclic sulfonyl, non-aromatic heterocyclic sulfonyl which may be substituted with substituent group A, aromatic carbocyclic amino which may be substituted with substituent group A, may be substituted with substituent group A. Good non-aromatic carbocyclic amino, aromatic heterocyclic amino which may be substituted with substituent group A, non-aromatic heterocyclic amino which may be substituted with substituent group A, even when substituted with substituent group A Good aromatic carbocyclic alkyl, non-aromatic carbocyclic alkyl which may be substituted with substituent group A, aromatic heterocyclic alkyl which may be substituted with substituent group A, may be substituted with substituent group A. Non-aromatic heterocyclic alkyl, aromatic carbocyclic alkyloxy optionally substituted with substituent group A, non-aromatic carbocyclic alkyloxy optionally substituted with substituent group A, substituted with substituent group A May be aromatic heterocyclic alkyloxy, non-aromatic heterocyclic alkyloxy which may be substituted with substituent group A, aromatic carbocyclic alkylcarbonyl which may be substituted with substituent group A, substituted with substituent group A. May be non-aromatic carbocyclic alkylcarbonyl, substituents Aromatic heterocyclic alkylcarbonyl optionally substituted with group A, non-aromatic heterocyclic alkylcarbonyl optionally substituted with substituent group A, aromatic carbocyclic alkyloxycarbonyl optionally substituted with substituent group A , Non-aromatic carbocyclic alkyloxycarbonyl which may be substituted with substituent group A, aromatic heterocyclic alkyloxycarbonyl which may be substituted with substituent group A, non-aromatic which may be substituted with substituent group A. Group heterocyclic alkyloxycarbonyl, aromatic carbocyclic alkyl sulfanyl optionally substituted with substituent group A, non-aromatic carbocyclic alkyl sulfanyl optionally substituted with substituent group A, substituted with substituent group A May be aromatic heterocyclic alkylsulfanyl, non-aromatic heterocyclic alkylsulfanyl which may be substituted with substituent group A, aromatic carbocyclic alkylsulfinyl which may be substituted with substituent group A, substituted with substituent group A. Non-aromatic carbocyclic alkyl sulfinyl which may be substituted, aromatic heterocyclic alkylsulfinyl which may be substituted with substituent group A, non-aromatic heterocyclic alkylsulfinyl which may be substituted with substituent group A, substituent group. Aromatic carbocyclic alkyl sulfonyls optionally substituted with A, non-aromatic carbocyclic alkyl sulfonyls optionally substituted with substituent group A, aromatic heterocyclic alkylsulfonyls optionally substituted with substituent group A, substituted. Non-aromatic heterocyclic alkylsulfonyls that may be substituted with group A, aromatic carbocyclic alkylaminos that may be substituted with substituent group A, non-aromatic carbocyclic alkyls that may be substituted with substituents A. Amino, aromatic heterocyclic alkylamino which may be substituted with substituent group A, non-aromatic heterocyclic alkylamino which may be substituted with substituent group A, aromatic carbon which may be substituted with substituent group A. Ring alkylcarbonylamino, non-aromatic carbocyclic alkylcarbonylamino optionally substituted with substituent group A, aromatic heterocyclic alkylcarbonylamino optionally substituted with substituent group A, substituted with substituent group A May be non-aromatic heterocyclic alkylcarbonylamino, aromatic carbocyclic alkyloxycarbonylamino which may be substituted with substituent group A, non-aromatic carbocyclic alkyloxycarbonylamino which may be substituted with substituent group A, Aromatic heterocyclic alkyloxycarbonylamino which may be substituted with substituent group A, non-aromatic heterocyclic alkyloxycarbonylamino which may be substituted with substituent group A, fragrance which may be substituted with substituent group A. Group carbocyclic alkylsulfonylamino, located in substituent group A A non-aromatic carbon ring alkylsulfonylamino that may be converted, an aromatic heterocyclic alkylsulfonylamino that may be substituted with a substituent group A, a non-aromatic heterocyclic alkylsulfonylamino that may be substituted with a substituent group A. , Aromatic carbocyclic oxyalkylamino which may be substituted with substituent group A, non-aromatic carbocyclic oxyalkylamino which may be substituted with substituent group A, aromatic which may be substituted with substituent group A. A non-aromatic heterocyclic oxyalkylamino which may be substituted with a heterocyclic oxyalkylamino and a substituent group A.

The embodiments and preferred embodiments of each substituent in the compound represented by the formula (I) or (I') are shown below. Compounds of possible combinations of the respective embodiments of each substituent shown below are preferred.

で示される部分の好ましい態様としては、

が挙げられ、更に好ましい態様としては、

が挙げられ、

が特に好ましい。 formula:

As a preferred embodiment of the portion indicated by,

Is mentioned, and as a more preferable embodiment,

Is mentioned,

Is particularly preferable.

Examples of X include C (= O), C (= S), or SO ₂ .
Preferred embodiments of X include C (= O) and C (= S).
A more preferred embodiment of X is C (= O).

R ¹ includes hydrogen, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocycle. Formula groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, Substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted Alternatively, an unsubstituted non-aromatic heterocyclic oxycarbonyl, a substituted or unsubstituted aromatic carbocyclic sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic sulfonyl, a substituted or unsubstituted aromatic heterocyclic sulfonyl, or a substituted or non-substituted aromatic heterocyclic sulfonyl. Substituted non-aromatic heterocyclic sulfonyls can be mentioned.
Preferred embodiments of R ¹ include hydrogen or hydroxy.
A more preferred embodiment of R ¹ is hydrogen.
Examples of substituents when R ¹ is substituted include halogen, hydroxy, amino, alkyl, monoalkylamino, dialkylamino, aromatic carbocyclic groups, non-aromatic carbocyclic groups, aromatic heterocycles. Examples include a formula group or a non-aromatic heterocyclic group.

であり、
Ｒ^2bは、水素、シアノ、置換もしくは非置換のカルバモイル、置換もしくは非置換のアルキル、置換もしくは非置換のアルケニル、置換もしくは非置換のアルキニル、または置換もしくは非置換のアルキルスルホニルである。
この場合、Ｒ^2bの更に好ましい態様としては、水素、または置換もしくは非置換のアルキルが挙げられ、特に、アルキル、ハロアルキルが好ましい。
なお、Ｒ^2bが置換されている場合の置換基の例としては、ハロゲンが挙げられる。 It is preferable that R ^2a and R ^2b form a ring B together with adjacent carbon atoms.
As another aspect of R ^2a and R ^2b , the following aspects are also preferred.
R ^2a is the formula:

And
R ^2b is hydrogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted alkylsulfonyl.
In this case, further preferred embodiments of R ^2b include hydrogen or substituted or unsubstituted alkyl, and alkyl and haloalkyl are particularly preferable.
Halogen is mentioned as an example of the substituent when R ^2b is substituted.

が挙げられる。
環Ｂの更に好ましい態様としては、式：

が挙げられる。
環Ｂの特に好ましい態様としては、式：

が挙げられる。
環Ｂの別の好ましい態様としては、式：

が挙げられ、更に好ましくは、式：

が挙げられる。
環Ｂの別の特に好ましい態様としては、式：

が挙げられる。
環Ｂの好ましい具体的な態様としては、式：

が挙げられる。
環Ｂの好ましい別の具体的な態様としては、式：

が挙げられる。 A preferred embodiment of the ring B is the formula:

Can be mentioned.
A more preferred embodiment of the ring B is the formula:

Can be mentioned.
A particularly preferred embodiment of the ring B is the formula:

Can be mentioned.
Another preferred embodiment of ring B is the formula:

Is mentioned, and more preferably, the formula:

Can be mentioned.
Another particularly preferred embodiment of ring B is the formula:

Can be mentioned.
A preferred specific embodiment of the ring B is the formula:

Can be mentioned.
As another preferred specific embodiment of the ring B, the formula:

Can be mentioned.

が挙げられる。 In yet another embodiment of the ring B, the formula:

Can be mentioned.

A preferred embodiment of B ¹ is CR ^11a R ^11b .
More preferred embodiments of B ¹ include C, CR ^11a , CR ^11a R ^11b , NR ^11c , or N.

Examples of B ² include CR ^12a R ^12b , NR ^12c , O, or S.
Preferred embodiments of B ² include CR ^12a R ^12b , NR ^12c , or O.
Further preferred embodiments of B ² include C, CR ^12a or N.
A more preferred embodiment of B ² is C.

Examples of B ³ include CR ^13a R ^13b , NR ^13c , O, or S.
Preferred embodiments of B ³ include CR ^13a R ^13b , NR ^13c or O.
Further preferred embodiments of B ³ include C, CR ^13a , CR ^13a R ^13b or O.
Preferred specific embodiments of B ³ include, for example, CH ₂ , NMe, and O.

Examples of B ⁴ include CR ^14a R ^14b , NR ^14c , O, or S.
Preferred embodiments of B ⁴ include CR ^14a R ^14b , NR ^14c or O.
A more preferred embodiment of B ⁴ is CR ^14a R ^14b .
Preferred specific embodiments of B ⁴ include CH ₂ , CF ₂ , C (= O) or O.

Preferred embodiments of B ⁵ include CR ^15a R ^15b .

However, -B ¹ -B ² -B ³ -B ⁴ -or -B ¹ -B ² -B ³ -B ⁴ -B ⁵ --is -O-O-O-O- or -S-S-S. Unlike -S- and the like, three or more atoms of any one of N, O, and S are not continuously bonded.

Ｒ^11a、Ｒ^12a、Ｒ^13a、Ｒ^14a、およびＲ^15aの好ましい態様としては、それぞれ独立して、水素、ハロゲン、または置換もしくは非置換のアルキルが挙げられる。
Ｒ^11a、Ｒ^12a、Ｒ^13a、Ｒ^14a、およびＲ^15aの更に好ましい態様としては、水素またはハロゲンが挙げられる。
Ｒ^11a、Ｒ^12a、Ｒ^13a、Ｒ^14a、およびＲ^15aが置換されている場合の置換基は、それぞれ独立して、ハロゲン、ヒドロキシ、アミノ、アルキル、モノアルキルアミノ、ジアルキルアミノ、芳香族炭素環式基、非芳香族炭素環式基、芳香族複素環式基、または非芳香族複素環式基である。 R ^11a , R ^12a , R ^13a , R ^14a , and R ^15a are independently hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or Unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted. Alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted Alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted Alkenyl sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Group heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic complex Ring oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyl Oxy, substituted or unsubstituted non-aromatic heterocyclic carbonyl Oxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted Alternatively, an unsubstituted non-aromatic heterocyclic carbonyl, a substituted or unsubstituted aromatic carbocyclic oxycarbonyl, a substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, a substituted or unsubstituted aromatic heterocyclic oxycarbonyl, a substituted or Unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic charcoal Elementary ring sulfanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, Substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted Non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) -R ^S2 , formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (= ^N -RN) ₂ -RS The group represented by ^S1 can be mentioned.
Here, the formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , the formula: -LS (= O) (= ^N -RN) ^-RS1 , the formula: -N = The groups represented by ^S (= ^N -RN) ( ^-RS1 ) ^-RS2 and the formula: -S (= ^N -RN) ₂ -RS1 are groups having the following chemical structures, respectively.

Preferred embodiments of R ^11a , R ^12a , R ^13a , R ^14a , and R ^15a include, independently, hydrogen, halogen, or substituted or unsubstituted alkyl, respectively.
Further preferred embodiments of R ^11a , R ^12a , R ^13a , R ^14a , and R ^15a include hydrogen or halogen.
When R ^11a , R ^12a , R ^13a , R ^14a , and R ^15a are substituted, the substituents are independently halogen, hydroxy, amino, alkyl, monoalkylamino, dialkylamino, aromatic carbocycle. A formula group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic heterocyclic group.

R ^11b , R ^12b , R ^13b , R ^14b , and R ^15b are independently hydrogen, halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or Unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted. Alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted Alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted Alkenyl sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Group heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic complex Ring oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyl Oxy, substituted or unsubstituted non-aromatic heterocyclic carbonyl Oxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted Alternatively, an unsubstituted non-aromatic heterocyclic carbonyl, a substituted or unsubstituted aromatic carbocyclic oxycarbonyl, a substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, a substituted or unsubstituted aromatic heterocyclic oxycarbonyl, a substituted or Unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic charcoal Elementary ring sulfanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, Substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted Non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocyclic sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) -R ^S2 , formula: -LS (= O) (= ^N -RN) ^-RS1 , formula: -N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (= ^N -RN) ₂ -RS The group represented by ^S1 can be mentioned.
Preferred embodiments of R ^11b , R ^12b , R ^13b , R ^14b , and R ^15b include hydrogen, or halogen.
When R ^11b , R ^12b , R ^13b , R ^14b , and R ^15b are substituted, the substituents are independently halogen, hydroxy, amino, alkyl, monoalkylamino, dialkylamino, aromatic carbocycle. A formula group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic heterocyclic group.

R ^11c , R ^12c , R ^13c , R ^14c , and R ^15c are independently hydrogen, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or non-substituted, respectively. Substituted amino, substituted or unsubstituted ureid, substituted or unsubstituted guanidino, pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkenyl, substituted or unsubstituted. Alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted Alkyl sulfanyl, substituted or unsubstituted alkenyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted aromatic Carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted aromatics. Carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyl, Substituent or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or non-substituted Substituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfanyl, substituted or unsubstituted. Non-aromatic carousyl sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic Carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfin Examples include inyl, substituted or unsubstituted aromatic carbocyclic sulfonyls, substituted or unsubstituted non-aromatic carbocyclic sulfonyls, substituted or unsubstituted aromatic heterocyclic sulfonyls, or substituted or unsubstituted non-aromatic heterocyclic sulfonyls. Be done.
Preferred embodiments of R ^11c , R ^12c , R ^13c , R ^14c , and R ^15c include, independently, hydrogen, halogen, or substituted or unsubstituted alkyl, respectively.
Further preferred embodiments of R ^11c , R ^12c , R ^13c , R ^14c , and R ^15c include hydrogen.
When R ^11c , R ^12c , R ^13c , R ^14c , and R ^15c are substituted, the substituents are independently halogen, hydroxy, amino, alkyl, monoalkylamino, dialkylamino, aromatic carbocycle. A formula group, a non-aromatic carbocyclic group, an aromatic heterocyclic group, or a non-aromatic heterocyclic group.

R ^S1 and R ^S2 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or non-substituted. Substituted aromatic heterocyclic groups, or substituted or unsubstituted non-aromatic heterocyclic groups, or R ^S1 and R ^S2 bonded to the same sulfur atom are combined with the sulfur atom. May form a substituted or unsubstituted non-aromatic heterocycle.
Preferred embodiments of ^RS1 and ^RS2 include hydrogen or substituted or unsubstituted alkyl, respectively.
Further preferred embodiments of ^RS1 and ^RS2 include hydrogen.
Examples of substituents when R ^S1 and R ^S2 are substituted are, independently, halogen, hydroxy, amino, alkyl, alkyloxy, monoalkylamino, dialkylamino, aromatic carbocyclic groups, non-rex. Examples include aromatic carbocyclic groups, aromatic heterocyclic groups, or non-aromatic heterocyclic groups.

The ^RNs are independently hydrogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted. Aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted Examples include aromatic carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, or substituted or unsubstituted non-aromatic heterocyclic carbonyls.
Preferred embodiments of ^RN include, independently, hydrogen, or substituted or unsubstituted alkyl.
A more preferred embodiment of ^RN is each independently substituted or unsubstituted alkyl.
Examples of substituents when ^RN is substituted are, independently, halogen, hydroxy, amino, alkyl, alkyloxy, monoalkylamino, dialkylamino, aromatic carbocyclic group, non-aromatic carbon. Examples include a cyclic group, an aromatic heterocyclic group, a non-aromatic heterocyclic group, and the like.

Examples of L include single bond, alkylene or C (= O) independently of each other.
Preferred embodiments of L include single bonds or alkylenes independently of each other.
A more preferred embodiment of L is a single bond.

Examples of n include integers from 0 to 5.
A preferred embodiment of n is an integer of 0 to 3.
A more preferred embodiment of n is an integer of 0 to 2.
A more preferred embodiment of n is an integer of 1 to 2.

Examples of the ring C include an aromatic carbocycle, a non-aromatic carbocycle having 4 to 20 carbon atoms, an aromatic heterocycle, and a non-aromatic heterocycle.
Preferred embodiments of ring C include an aromatic carbocycle or an aromatic heterocycle.
More preferred embodiments of ring C include benzene, naphthalene, indan, pyridine, pyrimidine, pyrazole, piperidine, piperazine, benzodioxol, benzothiophene, or thiazole.
More preferred embodiments of ring C include benzene or pyridine.
A particularly preferred embodiment of ring C is benzene.

The R ^5s are independently halogen, hydroxy, cyano, carboxy, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted. Substituted ureides, substituted or unsubstituted guanidinos, pentafluorothios, sulfos, substituted or unsubstituted sulfamoyls, substituted or unsubstituted alkyls, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted. Alkenyloxy, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or non-substituted Substituent alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkenylsulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted Alkenylsulfonyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic complex Cyclic groups, substituted or unsubstituted aromatic carbocyclic oxys, substituted or unsubstituted non-aromatic carbocyclic oxys, substituted or unsubstituted aromatic heterocyclic oxys, substituted or unsubstituted non-aromatic heterocyclic oxys, Substituted or unsubstituted aromatic carbocyclic carbonyloxy, substituted or unsubstituted non-aromatic carbocyclic carbonyloxy, substituted or unsubstituted aromatic heterocyclic carbonyloxy, substituted or unsubstituted non-aromatic heterocyclic carbonyloxy, Substituted or unsubstituted aromatic carbocyclic carbonyls, substituted or unsubstituted non-aromatic carbocyclic carbonyls, substituted or unsubstituted aromatic heterocyclic carbonyls, substituted or unsubstituted non-aromatic heterocyclic carbonyls, substituted or unsubstituted. Aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic heterocyclic oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted. Aromatic carbocyclic sulfanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, also substituted Alternatively, unsubstituted aromatic heterocyclic sulfanyl, substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted. Aromatic heterocyclic sulfinyl, substituted or unsubstituted non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic carbocyclic sulfonyl, substituted or unsubstituted aromatic heterocycle. Ring sulfonyl, substituted or unsubstituted non-aromatic heterocyclic sulfonyl, formula: -L-N = S (= O) ( ^-RS1 ) ^-RS2 , formula: -LS (= O) (= N- RN) ^-RS1 , formula: ^-N = S (= ^N -RN) ( ^-RS1 ) ^-RS2 , or formula: -S (= ^N - ^RN ) ₂ -RS1 Can be mentioned.
Preferred embodiments of R ⁵ are independently halogen, cyano, substituted or unsubstituted carbamoyl, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted. Aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted. Non-aromatic carbocyclic oxy, or substituted or unsubstituted non-aromatic heterocyclic oxy.
In a more preferred embodiment of R ⁵ , each independently has a halogen, a cyano, a substituted or unsubstituted amino, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkyloxy, a substituted or unsubstituted aromatic carbocyclic ring formula. Group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted non-aromatic carbocyclic ring Examples include oxy, or substituted or unsubstituted non-aromatic heterocyclic oxy.
In a further preferred embodiment of R ⁵ , each independently is a halogen, a substituted or unsubstituted alkyl, a substituted or unsubstituted alkyloxy, a substituted or unsubstituted aromatic carbocyclic group, a substituted or unsubstituted non-fragrance. Group carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted non-aromatic carbocyclic oxy, or substituted or unsubstituted non-substituted. Aromatic heterocyclic oxy can be mentioned.
Particularly preferred embodiments of R ⁵ are halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic carbocyclic groups, or substituted or unsubstituted non-aromatic heterocycles. The formula group is mentioned.
Examples of substituents when R ⁵ is substituted include halogen, alkyl, haloalkyl, cyanoalkyl, alkyloxyalkyl, haloalkylcarbonyl, non-aromatic carbocyclic groups, non-aromatic heterocyclic groups, non-aromatic groups. Examples thereof include group carbocyclic alkyl, aromatic heterocyclic alkyl, and non-aromatic heterocyclic alkyl.

Examples of R ^3a include hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted. Unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic group oxy, substituted Alternatively, an unsubstituted non-aromatic carbocyclic group oxy, a substituted or unsubstituted aromatic heterocyclic group oxy, a substituted or unsubstituted non-aromatic heterocyclic group oxy, a substituted or unsubstituted aromatic carbocyclic group oxy. Examples include a group sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic group sulfonyl, a substituted or unsubstituted aromatic heterocyclic group sulfonyl, or a substituted or unsubstituted non-aromatic heterocyclic group sulfonyl.
Preferred embodiments of R ^3a include hydrogen.
Examples of substituents when R ^3a is substituted include halogen, hydroxy, amino, alkyl, monoalkylamino, dialkylamino, aromatic carbocyclic groups, non-aromatic carbocyclic groups, aromatic heterocycles. Examples include a formula group or a non-aromatic heterocyclic group.

R ^3b includes hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted. Unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic group oxy, substituted Alternatively, an unsubstituted non-aromatic carbocyclic group oxy, a substituted or unsubstituted aromatic heterocyclic group oxy, a substituted or unsubstituted non-aromatic heterocyclic group oxy, a substituted or unsubstituted aromatic carbocyclic group oxy. Examples include a group sulfonyl, a substituted or unsubstituted non-aromatic carbocyclic group sulfonyl, a substituted or unsubstituted aromatic heterocyclic group sulfonyl, or a substituted or unsubstituted non-aromatic heterocyclic group sulfonyl.
Preferred embodiments of R ^3b include hydrogen.
Examples of substituents when R ^3b is substituted are halogen, hydroxy, amino, alkyl, monoalkylamino, dialkylamino, aromatic carbocyclic groups, non-aromatic carbocyclic groups, aromatic heterocycles. Examples include a formula group or a non-aromatic heterocyclic group.

が挙げられる。
Ｒ^4aの別の好ましい態様としては、シアノ、

が挙げられる。
Ｒ^4aの更に好ましい態様としては、

が挙げられる。
Ｒ^4aのより好ましい態様としては、

が挙げられる。 A preferred embodiment of R ^4a is the formula:

Can be mentioned.
Another preferred embodiment of R ^4a is cyano,

Can be mentioned.
A more preferred embodiment of R ^4a is

Can be mentioned.
A more preferred embodiment of R ^4a is

Can be mentioned.

Preferred embodiments of R ^4b include substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups. Examples include groups or substituted or unsubstituted non-aromatic heterocyclic groups.
Examples of substituents when R ^4b is substituted are halogen, hydroxy, cyano, alkyl, alkenyl, haloalkyl, hydroxyalkyl, alkyloxy, haloalkyloxy, alkylsulfonyl, dialkylamino, substituted with substituent group B. It may be substituted with an aromatic carbocycle, a non-aromatic carbocycle which may be substituted with a substituent group B, an aromatic heterocycle which may be substituted with a substituent group B, and a substituent group B. Examples include non-aromatic heterocycles.
When R ^4b is substituted, preferred substituents are halogen, cyano, alkyl, haloalkyl, alkyloxy, haloalkyloxy, aromatic carbocycles which may be substituted with substituent group B, and substituents group B. Examples thereof include a non-aromatic carbocycle which may be substituted, an aromatic heterocycle which may be substituted with the substituent group B, and a non-aromatic heterocycle which may be substituted with the substituent group B.

Preferred embodiments of R ^4c include substituted or unsubstituted alkyl.

Preferred embodiments of R ^4c' include hydrogen, or substituted or unsubstituted alkyl.
When R ^4c or R ^4c'is substituted, the substituent includes halogen.

m is an integer of 0 to 3.
A preferred embodiment of m is 0 or 1.

Preferred embodiments of L ¹ include single bonds or alkylenes.
Further preferred embodiments of L ¹ include single bond and methylene.

Preferred embodiments of L ² are single bond, -C (= O) -O-, -N (H)-, -C (= O) -N (H)-, -N (H) -C (= O)-, -N (H) -C (= O) -N (H)-, -C (= O) -N (H) -S (= O) _2- , -N (H) -S ( = O) ₂ -or-N (H) -S (= O) ₂ -N (H)-.
More preferred embodiments of L ² are single bond, -C (= O)-, -C (= O) -N (H)-, -N (H) -C (= O)-, -C (=). O) -N (H) -S (= O) _2- or -N (H) -S (= O) _2- .
A more preferred embodiment of L ² is -N (H)-, -C (= O) -N (H)-, -N (H) -C (= O)-, or -C (= O)-. Examples include N (H) -S (= O) _2- .

A preferred embodiment of L ³ is an alkylene that may be single bond or substituted with halogen or hydroxy.
Preferred specific embodiments of L ³ include single bonds, methylene, ethylene and propylene.

Examples of R ⁷ include hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkylamino. A sulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, or substituted or unsubstituted non-aromatic heterocyclic group. The formula group is mentioned.
Preferred embodiments of R ⁷ are hydrogen, halogen, hydroxy, cyano, substituted or unsubstituted amino, substituted or unsubstituted carbamoyl, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted. Alkyl sulfanyl, substituted or unsubstituted alkyl sulfinyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic Group heterocyclic groups, substituted or unsubstituted non-aromatic heterocyclic groups, substituted or unsubstituted non-aromatic carbocyclic sulfonyls, formulas: -N = S (= O) ( ^-RS1 ) ^-RS2 , Alternatively, the formula: -S (= O) (= ^N -RN) ^-RS1 can be mentioned.
More preferred embodiments of R ⁷ are hydrogen, halogen, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted. Substituted non-aromatic carbocyclic sulfonyls, or the formula: —S (= O) (= ^N —RN) ^—RS1 can be mentioned.
Examples of substituents when R ⁷ is substituted include oxo, halogen, cyano, hydroxy, alkyl, haloalkyl, alkyloxy, haloalkyloxy, hydroxyalkyl, alkylcarbonyl, or alkylsulfonyl.

Preferred embodiments of R ⁶ are, independently, halogen, cyano, hydroxy, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted carbamoyl, substituted or substituted. Unsubstituted sulfamoyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic group. Heterocyclic groups, substituted or unsubstituted non-aromatic carbocyclic oxys, substituted or unsubstituted non-aromatic heterocyclic oxys, substituted or unsubstituted non-aromatic carbocyclic sulfonyls, or substituted or unsubstituted non-aromatics. Examples include heterocyclic sulfonyls.
A further preferred embodiment of R ⁶ is an independently halogen, cyano, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aromatic carbocyclic ring formula. Group, substituted or unsubstituted non-aromatic carbocyclic group, substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic oxy , Substituent or unsubstituted non-aromatic carbocyclic oxy, substituted or unsubstituted aromatic heterocyclic oxy or substituted or unsubstituted non-aromatic heterocyclic oxy.
In a more preferred embodiment of R ⁶ , each independently has a non-aromatic carbocyclic group which may be substituted with halogen, haloalkyl, haloalkyloxy, halogen or haloalkyl, or a non-aromatic which may be substituted with halogen or haloalkyl. Group heterocyclic groups can be mentioned.
Examples of substituents when R ⁶ is substituted include halogen, alkyl, haloalkyl, cyanoalkyl, hydroxyalkyl, alkyloxy, haloalkyloxy, alkyloxyalkyl, haloalkylcarbonyl, alkyloxycarbonylalkyl, substituent group B. An aromatic carbocyclic group which may be substituted with, a non-aromatic carbocyclic group which may be substituted with a substituent group B, an aromatic heterocyclic group which may be substituted with a substituent group B, a substituent. Non-aromatic heterocyclic group optionally substituted with group B, aromatic carbocyclic oxy optionally substituted with substituent group B, non-aromatic carbocyclic oxy optionally substituted with substituent group B, substituted Examples include aromatic heterocyclic oxy which may be substituted with group B and non-aromatic heterocyclic oxy which may be substituted with substituent group B.

Examples of R ¹⁶ include hydrogen, substituted or unsubstituted carbamoyl, substituted or unsubstituted thiocarbamoyl, substituted or unsubstituted amidino, substituted or unsubstituted amino, substituted or unsubstituted ureido, substituted or unsubstituted guanidino, and the like. Pentafluorothio, sulfo, substituted or unsubstituted sulfamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkylcarbonyl. , Substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkylsulfinyl. , Substituted or unsubstituted alkenyl sulfinyl, substituted or unsubstituted alkyl sulfonyl, substituted or unsubstituted alkenyl sulfonyl, substituted or unsubstituted aromatic carbocyclic group, substituted or unsubstituted non-aromatic carbocyclic group, Substituted or unsubstituted aromatic heterocyclic group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic oxy, substituted or unsubstituted non-aromatic carbocyclic oxy, substituted or Unsubstituted aromatic heterocyclic oxy, substituted or unsubstituted non-aromatic heterocyclic oxy, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic Group heterocyclic carbonyl, substituted or unsubstituted non-aromatic heterocyclic carbonyl, substituted or unsubstituted aromatic carbocyclic oxycarbonyl, substituted or unsubstituted non-aromatic carbocyclic oxycarbonyl, substituted or unsubstituted aromatic complex Ring oxycarbonyl, substituted or unsubstituted non-aromatic heterocyclic oxycarbonyl, substituted or unsubstituted aromatic carbocyclic sulfanyl, substituted or unsubstituted non-aromatic carbocyclic sulfanyl, substituted or unsubstituted aromatic heterocyclic sulfanyl , Substituted or unsubstituted non-aromatic heterocyclic sulfanyl, substituted or unsubstituted aromatic carbocyclic sulfinyl, substituted or unsubstituted non-aromatic carbocyclic sulfinyl, substituted or unsubstituted aromatic heterocyclic sulfinyl, substituted or non-substituted Substituent non-aromatic heterocyclic sulfinyl, substituted or unsubstituted aromatic carbocyclic sulfonyl, substituted or unsubstituted non-aromatic charcoal Examples include prime ring sulfonyls, substituted or unsubstituted aromatic heterocyclic sulfonyls, substituted or unsubstituted non-aromatic heterocyclic sulfonyls and the like.
Preferred embodiments of R ¹⁶ include substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclic groups, substituted or unsubstituted non-aromatic carbocyclic groups, substituted or unsubstituted aromatic heterocyclic groups. Group, substituted or unsubstituted non-aromatic heterocyclic group, substituted or unsubstituted aromatic carbocyclic carbonyl, substituted or unsubstituted non-aromatic carbocyclic carbonyl, substituted or unsubstituted aromatic heterocyclic carbonyl, or Examples include substituted or unsubstituted non-aromatic heterocyclic carbonyls.
Preferred embodiments of R ¹⁶ include substituted or unsubstituted alkyl, aromatic carbocyclic groups optionally substituted with substituent group B, non-aromatic carbocyclic groups optionally substituted with substituent group B, and the like. An aromatic heterocyclic group which may be substituted with a substituent group B, a non-aromatic heterocyclic group which may be substituted with a substituent group B, and an aromatic carbocyclic carbonyl which may be substituted with a substituent group B. , A non-aromatic carbocyclic carbonyl that may be substituted with substituent group B, an aromatic heterocyclic carbonyl that may be substituted with substituent group B, or a non-aromatic heterocycle that may be substituted with substituent group B. Carbonyl is mentioned.
Examples of substituents when R ¹⁶ is substituted include halogen, alkyl, haloalkyl, aromatic carbocyclic groups which may be substituted with substituent group B, and non-substituted groups which may be substituted with substituent group B. Examples thereof include an aromatic carbocyclic group, an aromatic heterocyclic group which may be substituted with a substituent group B, and a non-aromatic heterocyclic group which may be substituted with a substituent group B.

A feature of the compound according to the present invention is that the ring A is condensed with a monocycle such as dihydropyridone of the formula (I) or (I') to have an MGAT2 inhibitory action. Another feature is that the enone structure can be avoided and toxicity can be suppressed by condensing the ring A with a monocycle such as dihydropyridone.

The compound represented by the formula (I) or (I') is not limited to a specific isomer, and all possible isomers (eg, keto-enol isomer, imine-enamine isomer, diastereoisomer) are not limited to the specific isomers. Includes isomers, optical isomers, rotational isomers, etc.), racemates or mixtures thereof.

One or more hydrogen, carbon and / or other atoms of the compound of formula (I) or (I') may be substituted with isotopes of hydrogen, carbon and / or other atoms, respectively. Examples of such isotopes are ² H, ³ H, ¹¹ C, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, ¹⁷ O, ³¹ P, ³² P, ³⁵ S, ¹⁸ F, ¹²³ I and, respectively. ³⁶ Like Cl, hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine and chlorine are included. The compound represented by the formula (I) or (I') also includes a compound substituted with such an isotope. The isotope-substituted compounds are also useful as pharmaceuticals and include all radiolabeled compounds of the compounds of formula (I) or (I'). A "radiolabeling method" for producing the "radiolabeled body" is also included in the present invention, and the "radiolabeled body" is useful as a tool for research and / or diagnosis in metabolic pharmacokinetics research, binding assay. Is.

The radiolabeled compound represented by the formula (I) or (I') can be prepared by a method well known in the art. For example, a tritium-labeled compound represented by the formula (I) or (I') introduces tritium into a specific compound represented by the formula (I) or (I') by a catalytic dehalogenation reaction using tritium. Can be prepared by This method comprises a precursor and tritium in which the compound of formula (I) or (I') is appropriately halogenated in the presence or absence of a suitable catalyst, eg, Pd / C, base. Includes reacting with gas. Other suitable methods for preparing tritium-labeled compounds can be referred to in "Isotopes in the Physical and Biomedical Sciences, Vol.1, Labeled Compounds (Part A), Chapter 6 (1987)". The ¹⁴ C-labeled compound can be prepared by using a raw material having ¹⁴ C carbon.

Examples of the pharmaceutically acceptable salt of the compound represented by the formula (I) or (I') include the compound represented by the formula (I), an alkali metal (for example, lithium, sodium, potassium, etc.), and alkaline soil. Kinds of metal (eg, calcium, barium, etc.), magnesium, transition metals (eg, zinc, iron, etc.), ammonia, organic bases (eg, trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, meglumin, ethylenediamine) , Ppyridine, picolin, quinoline, etc.) and salts with amino acids, or inorganic acids (eg, hydrochloric acid, sulfuric acid, nitrate, carbonic acid, hydrobromic acid, phosphoric acid, hydroiodic acid, etc.), and organic acids (eg, formic acid). , Acetic acid, propionic acid, trifluoroacetic acid, citric acid, lactic acid, tartaric acid, oxalic acid, maleic acid, fumaric acid, mandelic acid, glutaric acid, malic acid, benzoic acid, phthalic acid, ascorbic acid, benzenesulfonic acid, p- Examples thereof include salts with toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, etc.). In particular, salts with hydrochloric acid, sulfuric acid, phosphoric acid, tartaric acid, methanesulfonic acid and the like can be mentioned. These salts can be formed by conventional methods.

When the compound represented by the formula (I) or (I') of the present invention or a pharmaceutically acceptable salt thereof forms a solvate (eg, hydrate, etc.), a co-crystal and / or a crystal polymorph. The present invention also includes such various solvates, co-crystals and crystal polymorphs. The "solvate" may be coordinated with any number of solvent molecules (eg, water molecules) with respect to the compound represented by the formula (I) or (I'). When the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof is left in the air, it may absorb water and adsorbed water may adhere to it or form a hydrate. In addition, a compound represented by the formula (I) or (I') or a pharmaceutically acceptable salt thereof may be recrystallized to form a polymorph. "Cocrystal" means that the compound or salt represented by the formula (I) or (I') and the counter molecule are present in the same crystal lattice, and may be formed with any number of counter molecules. ..

The compound represented by the formula (I) or (I') of the present invention or a pharmaceutically acceptable salt thereof may form a prodrug, and the present invention also includes various such prodrugs. A prodrug is a derivative of a compound according to the present invention having a group that can be chemically or metabolically decomposed, and is a compound according to the present invention that is pharmaceutically active in vivo by solvolysis or under physiological conditions. Is. The prodrug is hydrolyzed by a compound, gastric acid, etc., which is enzymatically oxidized, reduced, hydrolyzed, etc. under physiological conditions in the living body and converted into the compound represented by the formula (I) or (I'). It includes a compound converted into a compound represented by the formula (I) or (I') and the like. Methods for selecting and producing suitable prodrug derivatives are described, for example, in "Design of Prodrugs, Elsevier, Amsterdam, 1985". Prodrugs may have activity in themselves.

If the compound represented by the formula (I) or (I') or a pharmaceutically acceptable salt thereof has a hydroxyl group, for example, the compound having a hydroxyl group and a suitable acyl halide, a suitable acid anhydride, a suitable Examples thereof are prodrugs such as acyloxy derivatives and sulfonyloxy derivatives produced by reacting with a sulfonyl chloride, a suitable sulfonylan hydride and a mixed hydride, or by reacting with a condensing agent. For example, CH ₃ COO-, C ₂ H ₅ COO-, tert-BuCOO-, C ₁₅ H ₃₁ COO-, PhCOO-, (m-NaOOCPh) COO-, NaOOCCH ₂ CH ₂ COO-, CH ₃ CH (NH ₂ ). ) COO-, CH ₂ N (CH ₃ ) ₂ COO-, CH ₃ SO _3- , CH ₃ CH ₂ SO _3- , CF ₃ SO _3- , CH ₂ FSO _3- , CF ₃ CH ₂ SO _3- , p -CH ₃ O-PhSO _3- , PhSO _3- , p-CH ₃ PhSO _3- .

(Method for producing the compound of the present invention)
The compound represented by the formula (I) or (I') according to the present invention can be produced, for example, by a general synthetic method shown below. Extraction, purification, etc. may be performed by the treatment performed in a normal organic chemistry experiment.
The compound of the present invention can be synthesized with reference to a method known in the art.

（式中、Ｘ１は塩素、臭素、ヨウ素、トリフルオロメタンスルホナート；Ｘ２は塩素、臭素、ヨウ素；その他各記号は、前記と同意義である。）
工程１
化合物ａ１に化合物ａ２と塩基を反応させることで、化合物ａ３を得ることができる。
塩基としては、トリエチルアミン、ジイソプロピルエチルアミン、炭酸水素ナトリウム、炭酸セシウム、炭酸カリウムなどが挙げられる。
反応温度は０℃～１００℃である。
反応時間は１時間～１０時間である。
反応溶媒としてはメタノール、エタノール、テトラヒドロフラン等が挙げられる。
工程２
化合物ａ３に塩化銅や臭化銅などのハロゲン化剤と酸と亜硝酸ナトリウムなど水溶液を反応させることで、化合物ａ４を得ることができる。
酸としては、塩酸や酢酸などが挙げられる。
反応温度は０℃～１００℃である。
反応時間は１時間～１０時間である。
工程３
金属触媒および塩基存在下、化合物ａ４とボロン酸またはボロン酸エステルまたはトリアルキルスタンナンなどを反応させることにより、化合物ａ５を得ることができる。
金属触媒としては、酢酸パラジウム、ビス（ジベンジリデンアセトン）パラジウム、テトラキス（トリフェニルホスフィン）パラジウム、ビス（トリフェニルホスフィン）パラジウム（ＩＩ）二塩化物、ビス（トリ－ｔｅｒｔ－ブチルホスフィン）パラジウムなどが挙げられ、化合物ａ４に対して、０．００１～０．５モル当量用いることができる。
塩基として、水酸化リチウム、水酸化ナトリウム、水酸化カリウム、カリウムｔｅｒｔ－ブトキシド、ナトリウムｔｅｒｔ－ブトキシド、炭酸ナトリウム、炭酸カリウム、炭酸水素ナトリウム、リン酸ナトリウム、リン酸水素ナトリウム、リン酸カリウム、リン酸水素カリウム等が挙げられ、化合物ａ４に対して、１～１０モル当量用いることができる。
ボロン酸またはボロン酸エステルまたはトリアルキルスタンナンなどは、化合物ａ４に対して、１～１０モル当量用いることができる。
反応温度は、２０℃～溶媒の還流温度、場合によってはマイクロウェーブ照射下の温度で行う。
反応時間は、０．１～４８時間、好ましくは０．５時間～１２時間である。
反応溶媒としては、テトラヒドロフラン、トルエン、ＤＭＦ、ジオキサン、水等が挙げられ、単独または混合して用いることができる。
なお、アミンまたはイミンまたはシアン化カリウムなどと化合物ａ４を反応させることで、Ｒ^4aにアミンまたはイミンまたはシアンなどを有する化合物ａ５を合成することができる。
また、Ｒ^4aがカルボニルアミノ、スルホニルアミノ等の場合は、化合物ａ３に種々官能基を付加することで合成できる。 (General synthesis method 1)
The compound represented by the formula (I) or (I') according to the present invention (hereinafter a5) can be produced, for example, by the following production method.

(In the formula, X1 is chlorine, bromine, iodine, trifluoromethanesulfonate; X2 is chlorine, bromine, iodine; and other symbols have the same meaning as described above.)
Process 1
Compound a3 can be obtained by reacting compound a1 with compound a2 and a base.
Examples of the base include triethylamine, diisopropylethylamine, sodium hydrogencarbonate, cesium carbonate, potassium carbonate and the like.
The reaction temperature is 0 ° C to 100 ° C.
The reaction time is 1 hour to 10 hours.
Examples of the reaction solvent include methanol, ethanol, tetrahydrofuran and the like.
Step 2
Compound a4 can be obtained by reacting compound a3 with a halogenating agent such as copper chloride or copper bromide with an acid and an aqueous solution such as sodium nitrite.
Examples of the acid include hydrochloric acid and acetic acid.
The reaction temperature is 0 ° C to 100 ° C.
The reaction time is 1 hour to 10 hours.
Process 3
Compound a5 can be obtained by reacting compound a4 with boronic acid, a boronic acid ester, trialkylstannan, or the like in the presence of a metal catalyst and a base.
Examples of the metal catalyst include palladium acetate, bis (dibenzylideneacetone) palladium, tetrakis (triphenylphosphine) palladium, bis (triphenylphosphine) palladium (II) dichloride, and bis (tri-tert-butylphosphine) palladium. As mentioned above, 0.001 to 0.5 molar equivalents can be used with respect to compound a4.
As bases, lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, sodium phosphate, sodium hydrogenphosphate, potassium phosphate, phosphate. Examples thereof include potassium hydrogen, and 1 to 10 mol equivalents can be used with respect to compound a4.
Boronic acid, boronic acid ester, trialkylstannan and the like can be used in an amount of 1 to 10 molar equivalents with respect to compound a4.
The reaction temperature is 20 ° C. to the reflux temperature of the solvent, and in some cases, the temperature under microwave irradiation.
The reaction time is 0.1 to 48 hours, preferably 0.5 to 12 hours.
Examples of the reaction solvent include tetrahydrofuran, toluene, DMF, dioxane, water and the like, which can be used alone or in combination.
By reacting compound a4 with amine, imine, potassium cyanide, etc., compound a5 having amine, imine, cyanide, etc. in R ^4a can be synthesized.
When R ^4a is carbonylamino, sulfonylamino, etc., it can be synthesized by adding various functional groups to compound a3.

（式中、各記号は、前記と同意義である。）
工程１
化合物ａ１にヒドラジン水和物を反応させることで、化合物ａ６を得ることができる。
反応温度は０℃～１００℃である。
反応時間は１時間～２０時間である。
反応溶媒としてはメタノール、エタノール、テトラヒドロフラン等が挙げられる。
工程２
化合物ａ６に塩基とハロゲン化物など反応させることで、化合物ａ３を得ることができる。
塩基としては、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウム、トリエチルアミン、ジイソプロピルエチルアミン、水素化ナトリウムなどが挙げられる。
反応温度は０℃～１００℃である。
反応時間は１時間～１０時間である。
反応溶媒としてはテトラヒドロフラン、ジクロロメタン、ジメチルホルムアミド等が挙げられる。 (Another method)
The compound a3 can be produced, for example, by the following production method.

(In the formula, each symbol has the same meaning as above.)
Process 1
Compound a6 can be obtained by reacting compound a1 with hydrazine hydrate.
The reaction temperature is 0 ° C to 100 ° C.
The reaction time is 1 to 20 hours.
Examples of the reaction solvent include methanol, ethanol, tetrahydrofuran and the like.
Step 2
Compound a3 can be obtained by reacting compound a6 with a base or a halide.
Examples of the base include sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, triethylamine, diisopropylethylamine, sodium hydride and the like.
The reaction temperature is 0 ° C to 100 ° C.
The reaction time is 1 hour to 10 hours.
Examples of the reaction solvent include tetrahydrofuran, dichloromethane, dimethylformamide and the like.

（式中、Ｘ３はＣ（＝Ｏ）、Ｃ（＝Ｓ）、またはＳＯ₂；その他各記号は、前記と同意義である。）
工程１
化合物ａ１に化合物ｂ１と塩基を反応させることで、化合物ｂ２を得ることができる。
塩基としては、ＤＢＵ、トリエチルアミン、ジイソプロピルエチルアミン、炭酸水素ナトリウムなどが挙げられる。
反応温度は０℃～１５０℃である。
反応時間は３０分～１０時間である。
反応溶媒としてはメタノール、エタノール、テトラヒドロフラン等が挙げられる。
工程２
塩基の存在下、化合物ｂ２とカルボン酸塩化物、スルホン酸塩化物またはチオカルボン酸塩化物等を反応させることにより、化合物ｂ３を得ることができる。
塩基としては、ピリジン、ＤＩＥＡ、炭酸カリウム、炭酸水素ナトリウム、水素化ナトリウム、水酸化ナトリウム等が挙げられる。
反応温度は、０℃～１５０℃、好ましくは２０℃～１００℃である。
反応時間は、０．５時間～１２０時間、好ましくは１時間～７２時間である。
反応溶媒としては、アセトニトリル、テトラヒドロフラン、トルエン、ジクロロメタン等が挙げられる。

工程２の別法として、工程２’を取り得る。
工程２’
化合物ｂ２に、縮合剤の存在下、カルボン酸などを反応させ、必要に応じて塩基も作用させることで、化合物ｂ３を得ることができる。
縮合剤としては、ジシクロへキシルカルボジイミド、カルボニルジイミダゾール、ジシクロヘキシルカルボジイミド－Ｎ－ヒドロキシベンゾトリアゾール、ＥＤＣ、４－（４，６－ジメトキシ－１，３，５－トリアジン－２－イル）－４－メチルモルホリニウムクロリド、ＨＡＴＵ等が挙げられ、化合物ａ３に対して１～５モル当量用いることができる。
塩基としては、トリエチルアミン、ジイソプロピルエチルアミンなどが挙げられる。
反応温度は、－２０℃～６０℃、好ましくは０℃～３０℃である。
反応時間は、０．１時間～２４時間、好ましくは１時間～１２時間である。
反応溶媒としては、ＤＭＦ、ＤＭＡ、ＮＭＰ、テトラヒドロフラン、ジオキサン、ジクロロメタン、アセトニトリル等が挙げられ、単独または混合して用いることができる。 (General synthesis method 2)
The compound represented by the formula (I) or (I') according to the present invention (hereinafter b3) can be produced, for example, by the following production method.

(In the formula, X3 is C (= O), C (= S), or SO ₂ ; other symbols have the same meaning as described above.)
Process 1
Compound b2 can be obtained by reacting compound a1 with compound b1 and a base.
Examples of the base include DBU, triethylamine, diisopropylethylamine, sodium hydrogencarbonate and the like.
The reaction temperature is 0 ° C to 150 ° C.
The reaction time is 30 minutes to 10 hours.
Examples of the reaction solvent include methanol, ethanol, tetrahydrofuran and the like.
Step 2
Compound b3 can be obtained by reacting compound b2 with a carboxyl chloride, a sulfonate, a thiocarboxylate, or the like in the presence of a base.
Examples of the base include pyridine, DIEA, potassium carbonate, sodium hydrogen carbonate, sodium hydride, sodium hydroxide and the like.
The reaction temperature is 0 ° C. to 150 ° C., preferably 20 ° C. to 100 ° C.
The reaction time is 0.5 hours to 120 hours, preferably 1 hour to 72 hours.
Examples of the reaction solvent include acetonitrile, tetrahydrofuran, toluene, dichloromethane and the like.

As an alternative to step 2, step 2'can be taken.
Process 2'
Compound b3 can be obtained by reacting compound b2 with a carboxylic acid or the like in the presence of a condensing agent and allowing a base to act as necessary.
Condensing agents include dicyclohexylcarbodiimide, carbonyldiimidazole, dicyclohexylcarbodiimide-N-hydroxybenzotriazole, EDC, 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methyl. Examples thereof include morpholinium chloride, HATU and the like, and 1 to 5 mol equivalents can be used with respect to compound a3.
Examples of the base include triethylamine and diisopropylethylamine.
The reaction temperature is −20 ° C. to 60 ° C., preferably 0 ° C. to 30 ° C.
The reaction time is 0.1 hour to 24 hours, preferably 1 hour to 12 hours.
Examples of the reaction solvent include DMF, DMA, NMP, tetrahydrofuran, dioxane, dichloromethane, acetonitrile and the like, and they can be used alone or in combination.

（式中、Ｘ４は塩素、臭素、ヨウ素；その他各記号は、前記と同意義である。）
工程１
化合物ｃ１に化合物ｃ２および塩基を反応させることで、化合物ｃ３を得ることができる。
塩基としては、ＤＢＵ、トリエチルアミン、ジイソプロピルエチルアミン、炭酸水素ナトリウム、炭酸セシウムなどが挙げられる。
反応温度は０℃～１５０℃である。
反応時間は３０分～１０時間である。
反応溶媒としてはメタノール、エタノール、テトラヒドロフラン、アセトニトリル等が挙げられる。
工程２
化合物ｃ３に酢酸アンモニウムなどを反応させることで、化合物ｃ４を得ることができる。
反応温度は０℃～１５０℃である。
反応時間は３０分～１０時間である。
反応溶媒としてはトルエン等が挙げられる。
工程３
化合物ｃ４に、酸またはルイス酸を反応させることにより、化合物ｃ５を得ることができる。
酸としては、塩酸－酢酸エチル、塩酸－メタノール、塩酸－ジオキサン、硫酸、ギ酸、トリフルオロ酢酸等が挙げられる。ルイス酸としては、ヨウ化トリメチルシリル、ＢＢｒ₃、ＡｌＣｌ₃、ＢＦ₃・（Ｅｔ₂Ｏ）等が挙げられ、化合物ｃ４に対して１～１０モル当量用いることができる。
反応温度は、０℃～６０℃、好ましくは０℃～２０℃である。
反応時間は、０．５時間～１２時間、好ましくは１時間～６時間である。
反応溶媒としては、メタノール、エタノール、水、アセトン、アセトニトリル、ＤＭＦ等が挙げられ、単独または混合して用いることができる。
工程４
塩基の存在下、化合物ｃ５とクロロギ酸４－ニトロフェニルまたはＣＤＩまたはＴＣＤＩ等を反応させることにより、化合物ｃ６を得ることができる。
塩基としては、ピリジン、ＤＩＥＡ、トリエチルアミン等が挙げられる。
反応温度は、０℃～１５０℃、好ましくは２０℃～１００℃である。
反応時間は、０．５時間～１２０時間、好ましくは１時間～７２時間である。
反応溶媒としては、アセトニトリル、テトラヒドロフラン、トルエン、ジクロロメタン等が挙げられる。
工程５
化合物ｃ６にＮ－ブロモスクシンイミドまたはＮ－ヨードスクシンイミドなどのハロゲン化剤とを反応させることで、化合物ｃ７を得ることができる。
酸としては、塩酸や酢酸などが挙げられる。
反応温度は０℃～１００℃である。
反応時間は１時間～１０時間である。
反応溶媒としては、ジクロロメタン、ジメチルホルムアミド等が挙げられる。
工程６
金属触媒および塩基存在下、化合物ｃ７とボロン酸またはボロン酸エステルまたはトリアルキルスタンナンなどを反応させることにより、化合物ｃ８を得ることができる。
金属触媒としては、酢酸パラジウム、ビス（ジベンジリデンアセトン）パラジウム、テトラキス（トリフェニルホスフィン）パラジウム、ビス（トリフェニルホスフィン）パラジウム（ＩＩ）二塩化物、ビス（トリ－ｔｅｒｔ－ブチルホスフィン）パラジウムなどが挙げられ、化合物ｃ７に対して、０．００１～０．５モル当量用いることができる。
塩基として、水酸化リチウム、水酸化ナトリウム、水酸化カリウム、カリウムｔｅｒｔ－ブトキシド、ナトリウムｔｅｒｔ－ブトキシド、炭酸ナトリウム、炭酸カリウム、炭酸水素ナトリウム、リン酸ナトリウム、リン酸水素ナトリウム、リン酸カリウム、リン酸水素カリウム等が挙げられ、化合物ｃ７に対して、１～１０モル当量用いることができる。
ボロン酸またはボロン酸エステルまたはトリアルキルスタンナンなどは、化合物ｃ７
に対して、１～１０モル当量用いることができる。
反応温度は、２０℃～溶媒の還流温度、場合によってはマイクロウェーブ照射下の温度で行う。
反応時間は、０．１～４８時間、好ましくは０．５時間～１２時間である。
反応溶媒としては、テトラヒドロフラン、トルエン、ＤＭＦ、ジオキサン、水等が挙げられ、単独または混合して用いることができる。
なお、アミンやイミン、シアン化カリウムなどと化合物ｃ７を反応させることで、Ｒ^4aにアミンまたはイミンまたはシアンなどを有する化合物ｃ８を合成することができる。 (General synthesis method 3)
The compound represented by the formula (I) or (I') according to the present invention (c8 below) can be produced, for example, by the following production method.

(In the formula, X4 is chlorine, bromine, iodine; other symbols have the same meaning as described above.)
Process 1
Compound c3 can be obtained by reacting compound c1 with compound c2 and a base.
Examples of the base include DBU, triethylamine, diisopropylethylamine, sodium hydrogencarbonate, cesium carbonate and the like.
The reaction temperature is 0 ° C to 150 ° C.
The reaction time is 30 minutes to 10 hours.
Examples of the reaction solvent include methanol, ethanol, tetrahydrofuran, acetonitrile and the like.
Step 2
Compound c4 can be obtained by reacting compound c3 with ammonium acetate or the like.
The reaction temperature is 0 ° C to 150 ° C.
The reaction time is 30 minutes to 10 hours.
Examples of the reaction solvent include toluene and the like.
Process 3
Compound c5 can be obtained by reacting compound c4 with an acid or Lewis acid.
Examples of the acid include hydrochloric acid-ethyl acetate, hydrochloric acid-methanol, hydrochloric acid-dioxane, sulfuric acid, formic acid, trifluoroacetic acid and the like. Examples of the Lewis acid include trimethylsilyl iodide, BBr ₃ , AlCl ₃ , BF ₃ · (Et ₂ O) and the like, and 1 to 10 molar equivalents can be used with respect to compound c4.
The reaction temperature is 0 ° C to 60 ° C, preferably 0 ° C to 20 ° C.
The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours.
Examples of the reaction solvent include methanol, ethanol, water, acetone, acetonitrile, DMF and the like, and they can be used alone or in combination.
Step 4
Compound c6 can be obtained by reacting compound c5 with 4-nitrophenyl chloroformate, CDI, TCDI, or the like in the presence of a base.
Examples of the base include pyridine, DIEA, triethylamine and the like.
The reaction temperature is 0 ° C. to 150 ° C., preferably 20 ° C. to 100 ° C.
The reaction time is 0.5 hours to 120 hours, preferably 1 hour to 72 hours.
Examples of the reaction solvent include acetonitrile, tetrahydrofuran, toluene, dichloromethane and the like.
Step 5
Compound c7 can be obtained by reacting compound c6 with a halogenating agent such as N-bromosuccinimide or N-iodosuccinimide.
Examples of the acid include hydrochloric acid and acetic acid.
The reaction temperature is 0 ° C to 100 ° C.
The reaction time is 1 hour to 10 hours.
Examples of the reaction solvent include dichloromethane, dimethylformamide and the like.
Step 6
Compound c8 can be obtained by reacting compound c7 with boronic acid, a boronic acid ester, trialkylstannan, or the like in the presence of a metal catalyst and a base.
Examples of the metal catalyst include palladium acetate, bis (dibenzylideneacetone) palladium, tetrakis (triphenylphosphine) palladium, bis (triphenylphosphine) palladium (II) dichloride, and bis (tri-tert-butylphosphine) palladium. As mentioned above, 0.001 to 0.5 molar equivalents can be used with respect to compound c7.
As bases, lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate, sodium phosphate, sodium hydrogenphosphate, potassium phosphate, phosphate. Examples thereof include potassium hydrogen, and 1 to 10 mol equivalents can be used with respect to compound c7.
Boronic acid or boronic acid ester or trialkylstannan and the like can be compounded with compound c7.
However, 1 to 10 molar equivalents can be used.
The reaction temperature is 20 ° C. to the reflux temperature of the solvent, and in some cases, the temperature under microwave irradiation.
The reaction time is 0.1 to 48 hours, preferably 0.5 to 12 hours.
Examples of the reaction solvent include tetrahydrofuran, toluene, DMF, dioxane, water and the like, which can be used alone or in combination.
By reacting compound c7 with amine, imine, potassium cyanide, etc., compound c8 having amine, imine, cyanide, etc. in R ^4a can be synthesized.

（式中、Ｍはリチウム、塩化マグネシウム、臭化マグネシウム、ヨウ化マグネシウム等；その他各記号は、前記と同意義である。）

工程１
化合物ｄ１と求核剤ｄ２を反応させることにより、化合物ｄ３を得ることができる。
求核剤ｄ２としては、メチルリチウム、エチルリチウム等のリチウム試薬やメチル臭化マグネシウム、メチル塩化マグネシウム、メチルヨウ化マグネシウム、エチル臭化マグネシウム、エチル塩化マグネシウム、エチルヨウ化マグネシウム等のグリニャール試薬およびこれらと金属塩の混合試薬が挙げられ、化合物ａ１に対して、１～５モル当量用いることができる。
反応温度は、－７８℃～溶媒の還流温度、好ましくは－４５℃～０℃である。
反応時間は、０．５～２４時間、好ましくは１時間～６時間である。
反応溶媒としては、テトラヒドロフラン、ヘキサン、ジエチルエーテル、メチルｔｅｒｔ－ブチルエーテル、トルエン、ジクロロメタン等が挙げられ、単独または混合して用いることができる。
求核剤ｄ２は、ハロゲン化物をｎ－ブチルリチウム等のアルキルリチウムを用いてリチオ化することにより、調整することができる。
反応溶媒としては、テトラヒドロフラン、ジオキサンなどアルキルリチウムと反応しない溶媒でなければ特に限定されない。リチオ化反応の温度は、－７８℃～０℃程度が好ましい。
なお、アルキル化などの反応を連続して行うことでＲ¹がアルキルなどの化合物を合成することができる。
工程２
化合物ｄ３を含む溶媒に、オゾンガスを導入し反応させた後、酸化的処理または還元的処理を行うことにより、化合物ｄ４を得ることができる。
反応温度は、－７８℃～－１５℃、好ましくは－７８℃～－４０℃である。
反応時間は、反応液の色が青色を帯びるまで反応させればよい。
酸化的処理としては、過酸化水素、クロム酸－硫酸等を使用することができる。
還元的処理としては、Ｚｎ－酢酸、（ＥｔＯ）₃Ｐ、接触水素添加、ジメチルスルフィド等を使用することができる。
反応溶媒としては、ジクロロメタン、メタノール、エタノール、酢酸エチル等が挙げられる。
工程３
化合物ｄ４と求核剤ｄ５を反応させることにより、化合物ｄ６を得ることができる。
求核剤ｄ５としては、メチルリチウム、エチルリチウム等のリチウム試薬やメチル臭化マグネシウム、メチル塩化マグネシウム、メチルヨウ化マグネシウム、エチル臭化マグネシウム、エチル塩化マグネシウム、エチルヨウ化マグネシウム等のグリニャール試薬およびこれらと金属塩の混合試薬が挙げられ、化合物ｄ４に対して、１～５モル当量用いることができる。
反応温度は、－７８℃～溶媒の還流温度、好ましくは－４５℃～０℃である。
反応時間は、０．５～２４時間、好ましくは１時間～６時間である。
反応溶媒としては、テトラヒドロフラン、ヘキサン、ジエチルエーテル、メチルｔｅｒｔ－ブチルエーテル、トルエン、ジクロロメタン等が挙げられ、単独または混合して用いることができる。
求核剤ｄ５は、ハロゲン化物をｎ－ブチルリチウム等のアルキルリチウムを用いてリチオ化することにより、調整することができる。
反応溶媒としては、テトラヒドロフラン、ジオキサンなどアルキルリチウムと反応しない溶媒でなければ特に限定されない。リチオ化反応の温度は、－７８℃～０℃程度が好ましい。
なお、求核剤ｄ５の代わりに、水素化ホウ素ナトリウム、水素化ホウ素リチウム、水素化アルミニウムリチウム等の還元剤を作用させることで、Ｒ^3bが水素である化合物を得ることができる。
工程４
化合物ｄ６に、トリフェニルホスフィン、および縮合剤の存在下、化合物ｄ７を反応させることにより、化合物ｄ８を得ることができる。
縮合剤としては、ＤＥＡＤ、ＤＩＡＤ等が挙げられ、化合物ｄ６に対して１～５モル当量用いることができる。
反応温度は、０℃～６０℃、好ましくは１０℃～４０℃である。
反応時間は、０．１時間～１２時間、好ましくは０．２時間～６時間である。
反応溶媒としては、テトラヒドロフラン、ジオキサン、酢酸エチル、トルエン、アセトニトリル等が挙げられ、単独または混合して用いることができる。
工程５
化合物ｄ８に、酸またはルイス酸を反応させることにより、化合物ｄ９を得ることができる。
酸としては、塩酸－酢酸エチル、塩酸－メタノール、塩酸－ジオキサン、硫酸、ギ酸、トリフルオロ酢酸等が挙げられる。ルイス酸としては、ヨウ化トリメチルシリル、ＢＢｒ₃、ＡｌＣｌ₃、ＢＦ₃・（Ｅｔ₂Ｏ）等が挙げられ、化合物ｄ８に対して１～１０モル当量用いることができる。
反応温度は、０℃～６０℃、好ましくは０℃～２０℃である。
反応時間は、０．５時間～１２時間、好ましくは１時間～６時間である。
反応溶媒としては、メタノール、エタノール、水、アセトン、アセトニトリル、ＤＭＦ等が挙げられ、単独または混合して用いることができる。
工程６
化合物ｄ９を加熱することで、化合物ｄ１０を得ることができる。
反応時間は、０．５時間～１２時間、好ましくは１時間～６時間である。
反応温度は、５０℃～１２０℃、好ましくは６０℃～９０℃である。
反応溶媒としては、メタノール、エタノール、ＤＭＦ、テトラヒドロフラン等が挙げられ、単独または混合して用いることができる。 (General synthesis method 4)
The compound represented by the formula (I) or (I') according to the present invention (d10 below) can be produced, for example, by the following production method.

(In the formula, M is lithium, magnesium chloride, magnesium bromide, magnesium iodide, etc .; other symbols have the same meaning as described above.)

Process 1
Compound d3 can be obtained by reacting compound d1 with nucleophile d2.
Examples of the nucleating agent d2 include lithium reagents such as methyl lithium and ethyl lithium, Grignard reagents such as methyl magnesium bromide, magnesium chloride, magnesium methyl iodide, magnesium ethyl bromide, ethyl magnesium chloride and magnesium ethyl iodide, and metals thereof. Examples thereof include a salt mixing reagent, and 1 to 5 molar equivalents can be used with respect to compound a1.
The reaction temperature is −78 ° C. to the reflux temperature of the solvent, preferably −45 ° C. to 0 ° C.
The reaction time is 0.5 to 24 hours, preferably 1 to 6 hours.
Examples of the reaction solvent include tetrahydrofuran, hexane, diethyl ether, methyl tert-butyl ether, toluene, dichloromethane and the like, which can be used alone or in combination.
The nucleophile d2 can be adjusted by lithiolating the halide with an alkyllithium such as n-butyllithium.
The reaction solvent is not particularly limited as long as it is not a solvent that does not react with alkyllithium such as tetrahydrofuran and dioxane. The temperature of the lithiolysis reaction is preferably about −78 ° C. to 0 ° C.
It should be noted that R ¹ can synthesize a compound such as alkyl by continuously performing a reaction such as alkylation.
Step 2
Compound d4 can be obtained by introducing ozone gas into a solvent containing compound d3 and reacting it, and then performing an oxidative treatment or a reducing treatment.
The reaction temperature is −78 ° C. to −15 ° C., preferably −78 ° C. to −40 ° C.
The reaction time may be such that the reaction may be carried out until the color of the reaction solution becomes bluish.
As the oxidative treatment, hydrogen peroxide, chromic acid-sulfuric acid and the like can be used.
As the reducing treatment, Zn _- acetic acid, (EtO) 3P, catalytic hydrogenation, dimethyl sulfide and the like can be used.
Examples of the reaction solvent include dichloromethane, methanol, ethanol, ethyl acetate and the like.
Process 3
Compound d6 can be obtained by reacting compound d4 with nucleophile d5.
Examples of the nucleating agent d5 include lithium reagents such as methyl lithium and ethyl lithium, Grignard reagents such as methyl magnesium bromide, methyl magnesium chloride, magnesium iodide, magnesium bromide, ethyl magnesium chloride and magnesium ethyl iodide, and metals thereof. Examples thereof include a salt mixing reagent, and 1 to 5 molar equivalents can be used with respect to compound d4.
The reaction temperature is −78 ° C. to the reflux temperature of the solvent, preferably −45 ° C. to 0 ° C.
The reaction time is 0.5 to 24 hours, preferably 1 to 6 hours.
Examples of the reaction solvent include tetrahydrofuran, hexane, diethyl ether, methyl tert-butyl ether, toluene, dichloromethane and the like, which can be used alone or in combination.
The nucleophile d5 can be adjusted by lithiolating the halide with an alkyllithium such as n-butyllithium.
The reaction solvent is not particularly limited as long as it is not a solvent that does not react with alkyllithium such as tetrahydrofuran and dioxane. The temperature of the lithiolysis reaction is preferably about −78 ° C. to 0 ° C.
A compound in which R ^3b is hydrogen can be obtained by allowing a reducing agent such as sodium borohydride, lithium borohydride, or lithium aluminum hydride to act instead of the nucleophile d5.
Step 4
Compound d8 can be obtained by reacting compound d6 with compound d7 in the presence of triphenylphosphine and a condensing agent.
Examples of the condensing agent include DEAD and DIAD, and 1 to 5 molar equivalents can be used with respect to compound d6.
The reaction temperature is 0 ° C to 60 ° C, preferably 10 ° C to 40 ° C.
The reaction time is 0.1 hour to 12 hours, preferably 0.2 hour to 6 hours.
Examples of the reaction solvent include tetrahydrofuran, dioxane, ethyl acetate, toluene, acetonitrile and the like, which can be used alone or in combination.
Step 5
Compound d9 can be obtained by reacting compound d8 with an acid or Lewis acid.
Examples of the acid include hydrochloric acid-ethyl acetate, hydrochloric acid-methanol, hydrochloric acid-dioxane, sulfuric acid, formic acid, trifluoroacetic acid and the like. Examples of the Lewis acid include trimethylsilyl iodide, BBr ₃ , AlCl ₃ , BF ₃ · (Et ₂ O) and the like, and 1 to 10 molar equivalents can be used with respect to compound d8.
The reaction temperature is 0 ° C to 60 ° C, preferably 0 ° C to 20 ° C.
The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours.
Examples of the reaction solvent include methanol, ethanol, water, acetone, acetonitrile, DMF and the like, and they can be used alone or in combination.
Step 6
Compound d10 can be obtained by heating compound d9.
The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours.
The reaction temperature is 50 ° C to 120 ° C, preferably 60 ° C to 90 ° C.
Examples of the reaction solvent include methanol, ethanol, DMF, tetrahydrofuran and the like, which can be used alone or in combination.

（式中、Ｘ５はフッ素、塩素、臭素、ヨウ素；その他各記号は、前記と同意義である。）
工程１
化合物ｅ１に、塩基の存在下または非存在下、Ｂｏｃ₂Ｏを反応させることにより、化合物ｅ２を得ることができる。
塩基としては、水酸化ナトリウム、炭酸ナトリウム、炭酸水素ナトリウム、炭酸カリウム、炭酸カルシウム、炭酸セシウム、ピリジン、トリエチルアミン等が挙げられ、化合物a4に対して１～５モル当量用いることができる。
反応温度は、－１０℃～８０℃、好ましくは１０℃～６０℃である。
反応時間は、０．５時間～２４時間、好ましくは１～１２時間である。
反応溶媒としては、テトラヒドロフラン、ジオキサン、アセトニトリル、水等が挙げられ、単独または混合して用いることができる。
また、Ｂｏｃ以外の保護基として、Ｂｎ基、Ａｌｌｏｃ基、Ｆｍｏｃ基、Ｃｂｚ基、Ａｃ基、Ｔｒｏｃ基、メトキシカルボニル基、トリフルオロアセチル基などの他の保護基も用いることができる。
工程２
化合物ｅ２に、塩基性の水溶液を反応させることにより、化合物ｅ３を得ることができる。
反応温度は、０℃～４０℃、好ましくは０℃～２０℃である。
反応時間は、０．５時間～１２時間、好ましくは１時間～６時間である。
塩基としては、炭酸ナトリウム、炭酸カリウム、炭酸セシウム、水酸化リチウム、水酸化ナトリウム、水酸化カリウム等が挙げられる。
反応溶媒としては、メタノール、エタノール、水、アセトン、アセトニトリル、テトラヒドロフラン等が挙げられ、単独または混合して用いることができる。
工程３
化合物ｅ３に、縮合剤の存在下、メルドラム酸を反応させ、必要に応じて塩基も作用させ、その後加熱することで化合物ｅ４を得ることができる。
縮合剤としては、ジシクロへキシルカルボジイミド、カルボニルジイミダゾール、ジシクロヘキシルカルボジイミド－Ｎ－ヒドロキシベンゾトリアゾール、ＥＤＣ、４－（４，６－ジメトキシ－１，３，５－トリアジン－２－イル）－４－メチルモルホリニウムクロリド、ＨＡＴＵ等が挙げられ、化合物ｅ３に対して１～５モル当量用いることができる。
塩基としては、トリエチルアミン、ジイソプロピルエチルアミン、パラジメチルアミノピリジンなどが挙げられる。
反応温度は、縮合反応が－２０℃～６０℃、好ましくは０℃～３０℃であり、その後の加熱反応は５０℃～８０℃である。
反応時間は、縮合反応が０．１時間～２４時間、好ましくは１時間～１２時間であり、その後の加熱反応が２～５時間である。
反応溶媒としては、ＤＭＦ、ＤＭＡ、ＮＭＰ、テトラヒドロフラン、ジオキサン、ジクロロメタン、アセトニトリル、酢酸エチル等が挙げられ、単独または混合して用いることができる。
工程４
化合物ｅ４に塩基とハロゲン化物ｅ５を反応させることで、化合物ｅ６を得ることができる。
塩基としては、炭酸水素ナトリウム、炭酸ナトリウム、炭酸カリウム、炭酸セシウム、トリエチルアミン、ジイソプロピルエチルアミン、水素化ナトリウムなどが挙げられる。
反応温度は０℃～１００℃である。
反応時間は１時間～１０時間である。
反応溶媒としてはテトラヒドロフラン、ジクロロメタン、ジメチルホルムアミド等が挙げられる。
工程５
化合物ｅ６に、酸を反応させることにより、化合物ｅ７を得ることができる。
酸としては、塩酸、硫酸、メタンスルホン酸、トリフルオロ酢酸等が挙げられる。
反応温度は、０℃～６０℃、好ましくは０℃～２０℃である。
反応時間は、０．５時間～１２時間、好ましくは１時間～６時間である。
反応溶媒としては、メタノール、エタノール、水、アセトン、アセトニトリル、ＤＭＦ、ジクロロメタン等が挙げられ、単独または混合して用いることができる。
なお、アルキル化などの反応を連続して行うことでＲ¹がアルキルなどの化合物を合成することができる。 (General synthesis method 5)
The compound represented by the formula (I) or (I') according to the present invention (hereinafter e7) can be produced, for example, by the following production method.

(In the formula, X5 is fluorine, chlorine, bromine, iodine; other symbols have the same meaning as described above.)
Process 1
Compound e2 can be obtained by reacting compound e1 with Boc ₂ O in the presence or absence of a base.
Examples of the base include sodium hydroxide, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, calcium carbonate, cesium carbonate, pyridine, triethylamine and the like, and 1 to 5 molar equivalents can be used with respect to compound a4.
The reaction temperature is −10 ° C. to 80 ° C., preferably 10 ° C. to 60 ° C.
The reaction time is 0.5 to 24 hours, preferably 1 to 12 hours.
Examples of the reaction solvent include tetrahydrofuran, dioxane, acetonitrile, water and the like, which can be used alone or in combination.
Further, as a protective group other than Boc, other protective groups such as Bn group, Alloc group, Fmoc group, Cbz group, Ac group, Troc group, methoxycarbonyl group and trifluoroacetyl group can also be used.
Step 2
Compound e3 can be obtained by reacting compound e2 with a basic aqueous solution.
The reaction temperature is 0 ° C to 40 ° C, preferably 0 ° C to 20 ° C.
The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours.
Examples of the base include sodium carbonate, potassium carbonate, cesium carbonate, lithium hydroxide, sodium hydroxide, potassium hydroxide and the like.
Examples of the reaction solvent include methanol, ethanol, water, acetone, acetonitrile, tetrahydrofuran and the like, and they can be used alone or in combination.
Process 3
Compound e4 can be obtained by reacting compound e3 with Meldrum's acid in the presence of a condensing agent, allowing a base to act as necessary, and then heating the compound e3.
Condensing agents include dicyclohexylcarbodiimide, carbonyldiimidazole, dicyclohexylcarbodiimide-N-hydroxybenzotriazole, EDC, 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methyl. Examples thereof include morpholinium chloride, HATU and the like, and 1 to 5 mol equivalents can be used with respect to compound e3.
Examples of the base include triethylamine, diisopropylethylamine, paradimethylaminopyridine and the like.
The reaction temperature is −20 ° C. to 60 ° C., preferably 0 ° C. to 30 ° C. for the condensation reaction, and 50 ° C. to 80 ° C. for the subsequent heating reaction.
The reaction time is 0.1 to 24 hours for the condensation reaction, preferably 1 to 12 hours for the subsequent heating reaction, and 2 to 5 hours for the subsequent heating reaction.
Examples of the reaction solvent include DMF, DMA, NMP, tetrahydrofuran, dioxane, dichloromethane, acetonitrile, ethyl acetate and the like, and they can be used alone or in combination.
Step 4
Compound e6 can be obtained by reacting compound e4 with a base and a halide e5.
Examples of the base include sodium hydrogen carbonate, sodium carbonate, potassium carbonate, cesium carbonate, triethylamine, diisopropylethylamine, sodium hydride and the like.
The reaction temperature is 0 ° C to 100 ° C.
The reaction time is 1 hour to 10 hours.
Examples of the reaction solvent include tetrahydrofuran, dichloromethane, dimethylformamide and the like.
Step 5
Compound e7 can be obtained by reacting compound e6 with an acid.
Examples of the acid include hydrochloric acid, sulfuric acid, methanesulfonic acid, trifluoroacetic acid and the like.
The reaction temperature is 0 ° C to 60 ° C, preferably 0 ° C to 20 ° C.
The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours.
Examples of the reaction solvent include methanol, ethanol, water, acetone, acetonitrile, DMF, dichloromethane and the like, and they can be used alone or in combination.
It should be noted that R ¹ can synthesize a compound such as alkyl by continuously performing a reaction such as alkylation.

（式中、各記号は、前記と同意義である。）
化合物ｅ６に、アミンｆ１と酸を反応させることにより、化合物ｆ２を得ることができる。
酸としては、塩酸、硫酸、メタンスルホン酸、酢酸、トリフルオロ酢酸等が挙げられる。
反応温度は、０℃～１２０℃、好ましくは５０℃～１００℃である。
反応時間は、０．５時間～１２時間、好ましくは１時間～６時間である。
反応溶媒としては、トルエン、ベンゼン、テトラヒドロフラン等が挙げられ、単独または混合して用いることができる。
なお、アルキル化などの反応を連続して行うことでＲ¹がアルキルなどの化合物を合成することができる。 (General synthesis method 6)
The compound represented by the formula (I) or (I') according to the present invention (hereinafter f2) can be produced, for example, by the following production method.

(In the formula, each symbol has the same meaning as above.)
Compound f2 can be obtained by reacting compound e6 with amine f1 and an acid.
Examples of the acid include hydrochloric acid, sulfuric acid, methanesulfonic acid, acetic acid, trifluoroacetic acid and the like.
The reaction temperature is 0 ° C. to 120 ° C., preferably 50 ° C. to 100 ° C.
The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours.
Examples of the reaction solvent include toluene, benzene, tetrahydrofuran and the like, and they can be used alone or in combination.
It should be noted that R ¹ can synthesize a compound such as alkyl by continuously performing a reaction such as alkylation.

（式中、各記号は、前記と同意義である。）
化合物ｅ６に、硫化試薬を反応させることにより、化合物ｇ１を得ることができる。
硫化試薬としては、５硫化２リン、２，４－ビス（４－メトキシフェニル）－１，３，２，４－ジチアジホスフェタン－２，４－ジスルフィドなどが挙げられる。
反応温度は、０℃～１２０℃、好ましくは５０℃～１００℃である。
反応時間は、０．５時間～１２時間、好ましくは１時間～６時間である。
反応溶媒としては、トルエン、ベンゼン、テトラヒドロフラン等が挙げられ、単独または混合して用いることができる。
なお、アルキル化などの反応を連続して行うことでＲ¹がアルキルなどの化合物を合成することができる。 (General synthesis method 7)
The compound represented by the formula (I) or (I') according to the present invention (hereinafter g1) can be produced, for example, by the following production method.

(In the formula, each symbol has the same meaning as above.)
Compound g1 can be obtained by reacting compound e6 with a sulfurizing reagent.
Examples of the sulfurizing reagent include 2 phosphorus pentasulfide, 2,4-bis (4-methoxyphenyl) -1,3,2,4-dithiadiphosphethane-2,4-disulfide and the like.
The reaction temperature is 0 ° C. to 120 ° C., preferably 50 ° C. to 100 ° C.
The reaction time is 0.5 to 12 hours, preferably 1 to 6 hours.
Examples of the reaction solvent include toluene, benzene, tetrahydrofuran and the like, and they can be used alone or in combination.
It should be noted that R ¹ can synthesize a compound such as alkyl by continuously performing a reaction such as alkylation.

（式中、各記号は、前記と同意義である。）
工程１
化合物ｈ１に、還元剤を反応させることにより、化合物ｈ２を得ることができる。
還元剤としては、水素化ホウ素ナトリウム、水素化ホウ素リチウム、水素化アルミニウムリチウム等が挙げられ、化合物ｈ１に対して、１～１０モル当量用いることができる。
反応温度は、０℃～還流温度、好ましくは２０℃～還流温度である。
反応時間は、０．２時間～４８時間、好ましくは１時間～２４時間である。
反応溶媒としては、メタノール、エタノール、プロパノール、イソプロパノール、ブタノール、テトラヒドロフラン、ジエチルエーテル、ジクロロメタン、水等が挙げられ、単独または混合して用いることができる。
工程２
化合物ｈ２に、アリルアルコールと塩基を反応させることにより、化合物ｈ３を得ることができる。
塩基としては、カリウムｔｅｒｔ－ブトキシド、ナトリウムｔｅｒｔ－ブトキシド等が挙げられる。
反応温度は、０℃～１５０℃、好ましくは２０℃～８０℃である。
反応時間は、０．５時間～４８時間、好ましくは０．５時間～７時間である。
反応溶媒としては、ジメチルスルホキシド、テトラヒドロフラン等が挙げられる。
工程３
化合物ｈ３とデスマーチンペルヨージナンを反応させることにより、化合物ｈ４を得ることができる。
反応温度は、０℃～１００、好ましくは２０℃～５０℃である。
反応時間は、０．５時間～４８時間、好ましくは０．５時間～７時間である。
反応溶媒としては、ジクロロメタンなどが挙げられる。
工程４
化合物ｈ４に、ヒドロキシルアミンと酢酸ナトリウムを反応させることにより、化合物ｈ５を得ることができる。
反応温度は、０℃～１５０℃、好ましくは５０℃～１００℃である。
反応時間は、０．５時間～４８時間、好ましくは０．５時間～７時間である。
反応溶媒としては、エタノール、メタノールなどが挙げられる。
工程５
化合物ｈ５とヒドロキノンを反応させることにより、化合物ｈ６を得ることができる。
反応温度は、０℃～１５０℃、好ましくは５０℃～１００℃である。
反応時間は、０．５時間～４８時間、好ましくは１０時間～２４時間である。
反応溶媒としては、トルエンなどが挙げられる。
工程６
化合物ｈ６と金属触媒存在下、水素ガスを反応させることにより、化合物ｈ７を得ることができる。
金属触媒としては、パラジウム－炭素、ロジウム－炭素などが挙げられ、化合物ｈ６に対して、０．０１～１００重量パーセント用いることができる。
水素気圧は、１～５０気圧が挙げられる。
反応温度は、０℃～溶媒の還流温度、好ましくは２０℃～４０℃である。
反応時間は、０．５～７２時間、好ましくは１～１２時間である。
反応溶媒としては、メタノール、エタノール、プロパノール、イソプロパノール、ブタノール、テトラヒドロフラン、ジエチルエーテル、トルエン、酢酸エチル、酢酸、水等が挙げられ、単独または混合して用いることができる。
工程７
化合物ｈ７に、塩基の存在下または非存在下、Ｂｏｃ₂Ｏを反応させることにより、化合物ｈ８を得ることができる。
塩基としては、水酸化ナトリウム、炭酸ナトリウム、炭酸水素ナトリウム、炭酸カリウム、炭酸カルシウム、炭酸セシウム、ピリジン、トリエチルアミン等が挙げられ、化合物ｌ１に対して１～５モル当量用いることができる。
反応温度は、－１０℃～８０℃、好ましくは１０℃～６０℃である。
反応時間は、０．５時間～２４時間、好ましくは１～１２時間である。
反応溶媒としては、テトラヒドロフラン、ジオキサン、アセトニトリル、水等が挙げられ、単独または混合して用いることができる。
なお、アルキル化などの反応を連続して行うことでＲ¹がアルキルなどの化合物を合成することができる。
工程８
化合物ｈ８とデスマーチンペルヨージナンを反応させることにより、化合物ｈ９を得ることができる。
反応温度は、０℃～１００、好ましくは２０℃～５０℃である。
反応時間は、０．５時間～４８時間、好ましくは０．５時間～７時間である。
反応溶媒としては、ジクロロメタンなどが挙げられる。
工程９
化合物ｈ９に、２－メチル２－ブテン、リン酸二水素ナトリウムと亜塩素酸ナトリウムを反応させることにより、化合物ｈ１０を得ることができる。
反応温度は、０℃～１００、好ましくは２０℃～５０℃である。
反応時間は、０．５時間～４８時間、好ましくは０．５時間～７時間である。
反応溶媒としては、ｔｅｒｔ－ブタノールなどが挙げられる。
工程１０
化合物ｈ１０とヨウ化メチルと塩基を反応させることにより、化合物ｈ１１を得ることができる。
塩基としては、炭酸カリウム、炭酸セシウム、炭酸ナトリウム、炭酸水素ナトリウム、等が挙げられる。
反応温度は、０℃～１００℃、好ましくは２０℃～５０℃である。
反応時間は、０．５時間～４８時間、好ましくは０．５時間～１０時間である。
反応溶媒としては、ジメチルスルホキシド、テトラヒドロフラン、アセトン、ＤＭＦ、ＤＭＡ、ＮＭＰ等が挙げられる。
工程１１
化合物ｈ１１に、酸またはルイス酸を反応させることにより、化合物ｈ１２を得ることができる。
酸としては、塩酸－酢酸エチル、塩酸－メタノール、塩酸－ジオキサン、硫酸、ギ酸、濃塩酸トリフルオロ酢酸等が挙げられる。ルイス酸としては、ヨウ化トリメチルシリル、ＢＢｒ₃、ＡｌＣｌ₃、ＢＦ₃・（Ｅｔ₂Ｏ）等が挙げられ、化合物ｈ１１に対して１～１０モル当量用いることができる。
反応温度は、０℃～１００℃、好ましくは２０℃～５０℃である。
反応時間は、０．５時間～１５０時間、好ましくは１０時間～１００時間である。
反応溶媒としては、メタノール、エタノール、水、アセトン、アセトニトリル、ＤＭＦ等が挙げられ、単独または混合して用いることができる。
工程１２
塩基存在下または非存在下、化合物ｈ１２とカルボン酸塩化物、スルホン酸塩化物またはチオカルボン酸塩化物等を反応させることにより、化合物ｈ１３を得ることができる。
塩基としては、ピリジン、ＤＩＥＡ、炭酸カリウム、炭酸水素ナトリウム、水素化ナトリウム、水酸化ナトリウム等が挙げられる。
反応温度は、０℃～１５０℃、好ましくは２０℃～１００℃である。
反応時間は、０．５時間～４８時間、好ましくは１時間～２４時間である。
反応溶媒としては、アセトニトリル、テトラヒドロフラン、トルエン、ジクロロメタン、ジメチルアセトアミド、ジメチルホルムアミド等が挙げられる。

工程１２の別法として、工程１２’を取り得る。
工程１２’
塩基存在下または非存在下、化合物ｈ１２に、縮合剤とカルボン酸などを反応させることにより、化合物ａ１３を得ることができる。
縮合剤としては、ジシクロへキシルカルボジイミド、カルボニルジイミダゾール、ジシクロヘキシルカルボジイミド－Ｎ－ヒドロキシベンゾトリアゾール、ＥＤＣ、４－（４，６－ジメトキシ－１，３，５－トリアジン－２－イル）－４－メチルモルホリニウムクロリド、ＨＡＴＵ等が挙げられ、化合物ｈ１２に対して１～５モル当量用いることができる。
塩基としては、トリエチルアミン、ジイソプロピルエチルアミンなどが挙げられる。
反応温度は、－２０℃～６０℃、好ましくは０℃～３０℃である。
反応時間は、０．１時間～２４時間、好ましくは１時間～１２時間である。
反応溶媒としては、ＤＭＦ、ＤＭＡ、ＮＭＰ、テトラヒドロフラン、ジオキサン、ジクロロメタン、アセトニトリル等が挙げられ、単独または混合して用いることができる。
工程１３
化合物ｈ１３に塩基を反応させることで、化合物ｈ１４を得ることができる。
塩基としては、ピペリジン、ピロリジン、トリエチルアミン、ジイソプロピルエチルアミン、ナトリウムメトキシド、ナトリウムエトキシドなどが挙げられる。
反応温度は０℃～１００℃である。
反応時間は１時間～１０時間である。
反応溶媒としてはメタノール、エタノール、テトラヒドロフラン等が挙げられる。
工程１４
化合物ｈ１４を、一般合成法１記載の方法に従い反応させることにより、化合物ｈ１５を得ることができる。 (General synthesis method 8)
The compound represented by the formula (I) according to the present invention (h15 below) can be produced, for example, by the following production method.

(In the formula, each symbol has the same meaning as above.)
Process 1
Compound h2 can be obtained by reacting compound h1 with a reducing agent.
Examples of the reducing agent include sodium borohydride, lithium borohydride, lithium aluminum hydride and the like, and 1 to 10 molar equivalents can be used with respect to compound h1.
The reaction temperature is 0 ° C. to reflux temperature, preferably 20 ° C. to reflux temperature.
The reaction time is 0.2 hours to 48 hours, preferably 1 hour to 24 hours.
Examples of the reaction solvent include methanol, ethanol, propanol, isopropanol, butanol, tetrahydrofuran, diethyl ether, dichloromethane, water and the like, and they can be used alone or in combination.
Step 2
Compound h3 can be obtained by reacting compound h2 with allyl alcohol and a base.
Examples of the base include potassium tert-butoxide, sodium tert-butoxide and the like.
The reaction temperature is 0 ° C. to 150 ° C., preferably 20 ° C. to 80 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 0.5 hours to 7 hours.
Examples of the reaction solvent include dimethyl sulfoxide and tetrahydrofuran.
Process 3
Compound h4 can be obtained by reacting compound h3 with Dess-Martin peryodinane.
The reaction temperature is 0 ° C to 100, preferably 20 ° C to 50 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 0.5 hours to 7 hours.
Examples of the reaction solvent include dichloromethane and the like.
Step 4
Compound h5 can be obtained by reacting compound h4 with hydroxylamine and sodium acetate.
The reaction temperature is 0 ° C. to 150 ° C., preferably 50 ° C. to 100 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 0.5 hours to 7 hours.
Examples of the reaction solvent include ethanol, methanol and the like.
Step 5
Compound h6 can be obtained by reacting compound h5 with hydroquinone.
The reaction temperature is 0 ° C. to 150 ° C., preferably 50 ° C. to 100 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 10 hours to 24 hours.
Examples of the reaction solvent include toluene and the like.
Step 6
Compound h7 can be obtained by reacting compound h6 with hydrogen gas in the presence of a metal catalyst.
Examples of the metal catalyst include palladium-carbon, rhodium-carbon and the like, and 0.01 to 100% by weight of the compound h6 can be used.
The hydrogen pressure is 1 to 50 atm.
The reaction temperature is 0 ° C. to the reflux temperature of the solvent, preferably 20 ° C. to 40 ° C.
The reaction time is 0.5 to 72 hours, preferably 1 to 12 hours.
Examples of the reaction solvent include methanol, ethanol, propanol, isopropanol, butanol, tetrahydrofuran, diethyl ether, toluene, ethyl acetate, acetic acid, water and the like, which can be used alone or in combination.
Step 7
Compound h8 can be obtained by reacting compound h7 with Boc ₂ O in the presence or absence of a base.
Examples of the base include sodium hydroxide, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, calcium carbonate, cesium carbonate, pyridine, triethylamine and the like, and 1 to 5 molar equivalents can be used with respect to compound l1.
The reaction temperature is −10 ° C. to 80 ° C., preferably 10 ° C. to 60 ° C.
The reaction time is 0.5 to 24 hours, preferably 1 to 12 hours.
Examples of the reaction solvent include tetrahydrofuran, dioxane, acetonitrile, water and the like, which can be used alone or in combination.
It should be noted that R ¹ can synthesize a compound such as alkyl by continuously performing a reaction such as alkylation.
Step 8
Compound h9 can be obtained by reacting compound h8 with Dess-Martin peryodinane.
The reaction temperature is 0 ° C to 100, preferably 20 ° C to 50 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 0.5 hours to 7 hours.
Examples of the reaction solvent include dichloromethane and the like.
Step 9
Compound h10 can be obtained by reacting compound h9 with 2-methyl-2-butene, sodium dihydrogen phosphate and sodium chlorite.
The reaction temperature is 0 ° C to 100, preferably 20 ° C to 50 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 0.5 hours to 7 hours.
Examples of the reaction solvent include tert-butanol and the like.
Step 10
Compound h11 can be obtained by reacting compound h10 with methyl iodide and a base.
Examples of the base include potassium carbonate, cesium carbonate, sodium carbonate, sodium hydrogen carbonate, and the like.
The reaction temperature is 0 ° C to 100 ° C, preferably 20 ° C to 50 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 0.5 hours to 10 hours.
Examples of the reaction solvent include dimethyl sulfoxide, tetrahydrofuran, acetone, DMF, DMA, NMP and the like.
Step 11
Compound h12 can be obtained by reacting compound h11 with an acid or Lewis acid.
Examples of the acid include hydrochloric acid-ethyl acetate, hydrochloric acid-methanol, hydrochloric acid-dioxane, sulfuric acid, formic acid, concentrated trifluoroacetic acid hydrochloride and the like. Examples of the Lewis acid include trimethylsilyl iodide, BBr ₃ , AlCl ₃ , BF ₃ · (Et ₂ O) and the like, and 1 to 10 molar equivalents can be used with respect to compound h11.
The reaction temperature is 0 ° C to 100 ° C, preferably 20 ° C to 50 ° C.
The reaction time is 0.5 hours to 150 hours, preferably 10 hours to 100 hours.
Examples of the reaction solvent include methanol, ethanol, water, acetone, acetonitrile, DMF and the like, and they can be used alone or in combination.
Step 12
Compound h13 can be obtained by reacting compound h12 with a carboxyl chloride, a sulfonate, a thiocarboxylate, or the like in the presence or absence of a base.
Examples of the base include pyridine, DIEA, potassium carbonate, sodium hydrogen carbonate, sodium hydride, sodium hydroxide and the like.
The reaction temperature is 0 ° C. to 150 ° C., preferably 20 ° C. to 100 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 1 hour to 24 hours.
Examples of the reaction solvent include acetonitrile, tetrahydrofuran, toluene, dichloromethane, dimethylacetamide, dimethylformamide and the like.

As an alternative to step 12, step 12'can be taken.
Process 12'
Compound a13 can be obtained by reacting compound h12 with a condensing agent and a carboxylic acid in the presence or absence of a base.
Condensing agents include dicyclohexylcarbodiimide, carbonyldiimidazole, dicyclohexylcarbodiimide-N-hydroxybenzotriazole, EDC, 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methyl. Examples thereof include morpholinium chloride, HATU and the like, and 1 to 5 mol equivalents can be used with respect to compound h12.
Examples of the base include triethylamine and diisopropylethylamine.
The reaction temperature is −20 ° C. to 60 ° C., preferably 0 ° C. to 30 ° C.
The reaction time is 0.1 hour to 24 hours, preferably 1 hour to 12 hours.
Examples of the reaction solvent include DMF, DMA, NMP, tetrahydrofuran, dioxane, dichloromethane, acetonitrile and the like, and they can be used alone or in combination.
Step 13
Compound h14 can be obtained by reacting compound h13 with a base.
Examples of the base include piperidine, pyrrolidine, triethylamine, diisopropylethylamine, sodium methoxide, sodium ethoxide and the like.
The reaction temperature is 0 ° C to 100 ° C.
The reaction time is 1 hour to 10 hours.
Examples of the reaction solvent include methanol, ethanol, tetrahydrofuran and the like.
Step 14
Compound h15 can be obtained by reacting compound h14 according to the method described in General Synthesis Method 1.

（式中、各記号は、前記と同意義である。）
工程１
化合物ｊ１とメチル（トリフェニルホスフォラニリデン）アセテートを反応させることにより、化合物ｊ２を得ることができる。
反応温度は、０℃～２００℃、好ましくは２０℃～１５０℃である。
反応時間は、０．５時間～４８時間、好ましくは０．５時間～１２時間である。
反応溶媒としては、トルエン、ジメチルスルホキシド、テトラヒドロフラン等が挙げられる。
工程２
化合物ｊ２とアンモニアを反応させることにより、化合物ｊ３を得ることができる。
反応温度は、０℃～１５０℃、好ましくは２０℃～８０℃である。
反応時間は、０．５時間～４８時間、好ましくは０．５時間～７時間である。
反応溶媒としては、ジメチルスルホキシド、テトラヒドロフラン、ジエチルエーテル、トルエン等が挙げられる。
工程３
化合物ｊ３とカルボン酸塩化物、スルホン酸塩化物またはチオカルボン酸塩化物等を反応させ、必要に応じて塩基も作用させることで、化合物ｊ５を得ることができる。
塩基としては、ピリジン、ＤＩＥＡ、炭酸カリウム、炭酸水素ナトリウム、水素化ナトリウム、水酸化ナトリウム等が挙げられる。
反応温度は、０℃～１５０℃、好ましくは２０℃～１００℃である。
反応時間は、０．５時間～４８時間、好ましくは１時間～２４時間である。
反応溶媒としては、アセトニトリル、テトラヒドロフラン、トルエン、ジクロロメタンjジメチルアセトアミド、ジメチルホルムアミド等が挙げられる。

工程３の別法として、工程３’を取り得る。
工程３’
塩基存在下または非存在下、化合物ｊ３に、縮合剤とカルボン酸などを反応させることにより、化合物ｊ４を得ることができる。
縮合剤としては、ジシクロへキシルカルボジイミド、カルボニルジイミダゾール、ジシクロヘキシルカルボジイミド－Ｎ－ヒドロキシベンゾトリアゾール、ＥＤＣ、４－（４，６－ジメトキシ－１，３，５－トリアジン－２－イル）－４－メチルモルホリニウムクロリド、ＨＡＴＵ等が挙げられ、化合物ｊ３に対して１～５モル当量用いることができる。
塩基としては、トリエチルアミン、ジイソプロピルエチルアミンなどが挙げられる。
反応温度は、－２０℃～６０℃、好ましくは０℃～３０℃である。
反応時間は、０．１時間～２４時間、好ましくは１時間～１２時間である。
反応溶媒としては、ＤＭＦ、ＤＭＡ、ＮＭＰ、テトラヒドロフラン、ジオキサン、ジクロロメタン、アセトニトリル等が挙げられ、単独または混合して用いることができる。
工程４
化合物ｊ４に塩基を反応させることで、化合物ｊ５を得ることができる。
塩基としては、ピペリジン、ピロリジン、トリエチルアミン、ジイソプロピルエチルアミン、ナトリウムメトキシド、ナトリウムエトキシドなどが挙げられる。
反応温度は０℃～１００℃である。
反応時間は１時間～１０時間である。
反応溶媒としてはメタノール、エタノール、テトラヒドロフラン等が挙げられる。
工程５
化合物ｊ５を、一般合成法１記載の方法に従い反応させることにより、化合物ｊ６を得ることができる。 (General synthesis method 9)
The compound represented by the formula (I) or (I') according to the present invention (hereinafter j6) can be produced, for example, by the following production method.

(In the formula, each symbol has the same meaning as above.)
Process 1
Compound j2 can be obtained by reacting compound j1 with methyl (triphenylphosphinelidene) acetate.
The reaction temperature is 0 ° C. to 200 ° C., preferably 20 ° C. to 150 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 0.5 hours to 12 hours.
Examples of the reaction solvent include toluene, dimethyl sulfoxide, tetrahydrofuran and the like.
Step 2
Compound j3 can be obtained by reacting compound j2 with ammonia.
The reaction temperature is 0 ° C. to 150 ° C., preferably 20 ° C. to 80 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 0.5 hours to 7 hours.
Examples of the reaction solvent include dimethyl sulfoxide, tetrahydrofuran, diethyl ether, toluene and the like.
Process 3
Compound j5 can be obtained by reacting compound j3 with a carboxyl chloride, a sulfonate, a thiocarboxylate, or the like, and if necessary, allowing a base to act.
Examples of the base include pyridine, DIEA, potassium carbonate, sodium hydrogen carbonate, sodium hydride, sodium hydroxide and the like.
The reaction temperature is 0 ° C. to 150 ° C., preferably 20 ° C. to 100 ° C.
The reaction time is 0.5 hours to 48 hours, preferably 1 hour to 24 hours.
Examples of the reaction solvent include acetonitrile, tetrahydrofuran, toluene, dichloromethanej dimethylacetamide, dimethylformamide and the like.

As an alternative to step 3, step 3'can be taken.
Process 3'
Compound j4 can be obtained by reacting compound j3 with a condensing agent and a carboxylic acid in the presence or absence of a base.
Condensing agents include dicyclohexylcarbodiimide, carbonyldiimidazole, dicyclohexylcarbodiimide-N-hydroxybenzotriazole, EDC, 4- (4,6-dimethoxy-1,3,5-triazine-2-yl) -4-methyl. Examples thereof include morpholinium chloride, HATU and the like, and 1 to 5 mol equivalents can be used with respect to compound j3.
Examples of the base include triethylamine and diisopropylethylamine.
The reaction temperature is −20 ° C. to 60 ° C., preferably 0 ° C. to 30 ° C.
The reaction time is 0.1 hour to 24 hours, preferably 1 hour to 12 hours.
Examples of the reaction solvent include DMF, DMA, NMP, tetrahydrofuran, dioxane, dichloromethane, acetonitrile and the like, and they can be used alone or in combination.
Step 4
Compound j5 can be obtained by reacting compound j4 with a base.
Examples of the base include piperidine, pyrrolidine, triethylamine, diisopropylethylamine, sodium methoxide, sodium ethoxide and the like.
The reaction temperature is 0 ° C to 100 ° C.
The reaction time is 1 hour to 10 hours.
Examples of the reaction solvent include methanol, ethanol, tetrahydrofuran and the like.
Step 5
Compound j6 can be obtained by reacting compound j5 according to the method described in General Synthesis Method 1.

The compound according to the present invention has an MGAT2 inhibitory action and is a preventive agent for obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, hyperfatty acidemia, diabetes, arteriosclerosis, etc. Or it is useful as a therapeutic agent.
The compound according to the present invention has not only an MGAT2 inhibitory action but also a medicinal usefulness, and has any or all of the following excellent characteristics.
a) High metabolic stability.
b) Shows high solubility.
c) There is little concern about phototoxicity.
d) There is little concern about hepatotoxicity.
e) There is little concern about nephrotoxicity.
f) There is little concern about toxicity to the cardiovascular system.
g) There is little concern about gastrointestinal disorders.
h) There is little concern about drug interactions.
i) Highly orally absorbable.
j) The clearance is small.
k) Highly transferable to the target tissue.
l) Enzyme activity is strong.
m) There is little induction of drug-metabolizing enzymes.
n) Strong medicinal effect.
o) High selectivity of MGAT2 inhibitory action.
p) High chemical stability.

The pharmaceutical composition of the present invention can be administered by either an oral method or a parenteral method. Examples of the parenteral administration method include transdermal, subcutaneous, intravenous, intraarterial, intramuscular, intraperitoneal, transmucosal, inhalation, nasal, instillation, ear instillation, and intravaginal administration.

In the case of oral administration, according to the conventional method, solid preparations for internal use (eg tablets, powders, granules, capsules, pills, film preparations, etc.), liquid preparations for internal use (eg, suspensions, emulsions, elixirs, syrups, etc.) It may be prepared and administered in any commonly used dosage form such as an agent, a limonade agent, a liquor agent, an aromatic water agent, an extract agent, a decoction agent, a tincture agent, etc. The tablets may be sugar-coated tablets, film-coated tablets, enteric-coated tablets, sustained release tablets, troche tablets, sublingual tablets, buccal tablets, chewable tablets or orally disintegrating tablets, and powders and granules may be dry syrup. Capsules may be soft capsules, microcapsules or sustained release capsules.

In the case of parenteral administration, injections, instillations, external preparations (eg, eye drops, nasal drops, ear drops, aerosols, inhalants, lotions, injectables, coatings, gargling agents, enema agents, etc. Any commonly used dosage form such as ointment, plaster, jelly, cream, patch, pap, external powder, suppository, etc. can be suitably administered. The injection may be an emulsion of O / W, W / O, O / W / O, W / O / W type or the like.

Various pharmaceutical additives such as excipients, binders, disintegrants, and lubricants suitable for the dosage form may be mixed with the effective amount of the compound according to the present invention as necessary to prepare a pharmaceutical composition. can. Further, the pharmaceutical composition is a pharmaceutical composition for pediatrics, elderly people, severely ill patients or surgery by appropriately changing the effective amount, dosage form and / or various pharmaceutical additives of the compound according to the present invention. It can also be a thing. Pediatric pharmaceutical compositions are preferably administered to patients aged 12 or less than 15 years. In addition, the pediatric pharmaceutical composition can be administered to patients less than 27 days after birth, 28 days to 23 months after birth, 2 years to 11 years, or 12 to 16 years or 18 years. The pharmaceutical composition for the elderly is preferably administered to a patient aged 65 years or older.

The dose of the pharmaceutical composition of the present invention is preferably set in consideration of the age, body weight, type and degree of disease, administration route, etc. of the patient, but in the case of oral administration, it is usually 0.05 to 100 mg / mg. It is kg / day, preferably in the range of 0.1 to 10 mg / kg / day. In the case of parenteral administration, it is usually 0.005 to 10 mg / kg / day, preferably in the range of 0.01 to 1 mg / kg / day, although it varies greatly depending on the administration route. This may be administered once to several times a day.

The dose of the concomitant drug can be appropriately selected based on the clinically used dose. In addition, the compounding ratio of the compound according to the present invention and the concomitant drug can be appropriately selected depending on the administration target, administration route, target disease, symptom, combination and the like. For example, when the administration target is a human, 0.01 to 100 parts by weight of the concomitant drug may be used with respect to 1 part by weight of the compound according to the present invention.

The pharmaceutical composition of the present invention can also be used for obesity (provided that the patient has both type 2 diabetes and dyslipidemia and has a BMI of 25 kg / m ² or more even with diet and exercise therapy). It is valid.

The pharmaceutical composition of the present invention is also effective for severe obesity in which the effects of pre-applied diet therapy and exercise therapy are insufficient.

The pharmaceutical composition of the present invention can also be used in combination with other anti-obesity drugs (pharmaceutical compositions containing compounds having an anti-obesity effect, drugs that can be used for weight management in obesity and obesity). .. For example, by using a pharmaceutical composition containing a compound having an anti-obesity effect in combination with the compound according to the present invention, it can be used for prevention and / or treatment of obesity, weight management in obesity, and the like. Further, by using the pharmaceutical composition containing the compound according to the present invention in combination with the pharmaceutical composition containing a compound having an anti-obesity effect, it is used for prevention and / or treatment of obesity, weight management in obesity, and the like. be able to. In addition, the administration therapy of the pharmaceutical composition of the present invention can also be used in combination with diet therapy, drug therapy, exercise and the like.

The abbreviations used herein have the following meanings.
Ac: Acetyl Alloc: Allyloxycarbonyl Bn: BenzylBoc: tert-Butoxycarbonyl Cbz: Benzyloxycarbonyl CDI: Carbonyldiimidazole DBU: Diazabicycloundecene DEAD: diethylazodicarboxylate DIAD: Diisopropyldicarboxylate DIEA: N , N-diisopropylethylamine DMA: dimethylacetamide DMF: N, N-dimethylformamide DMSO: dimethylsulfoxide EDC: 1-ethyl-3- (3-dimethylaminopropyl) -carbodiimide Et: ethyl Fmoc: 9-fluorenylmethyloxy CarbonylHATU: O- (7-azabenzotriazole-1-yl) -1,1,3,3-tetramethyluronium hexafluorophosphate NMP: N-methylpyrrolidone TCDI: 1,1'-thiocarbonyldiimidazole Troc : 2,2,2-trichloroethoxycarbonyl

Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but the present invention is not limited thereto.

工程１
既知化合物１（WO2017069224A1）（５４．７ｍｇ、０．１４２ｍｍｏｌ）をテトラヒドロフラン（１．１ｍＬ）に溶解し、フェニルヒドラジン（２８μＬ、０．２８ｍｍｏｌ）を氷冷下で加えて、２０分間撹拌した。反応液にＤＩＥＡ（５０μＬ、０．２８ｍｍｏｌ）を氷冷下で加え、室温にて３時間撹拌した後、さらに７０℃にて１時間撹拌した。反応液の溶媒を減圧留去し、得られた残渣をカラムクロマトグラフィー（クロロホルム－メタノール）により精製し、化合物２（５９．４ｍｇ、収率９２％）を得た。
1H-NMR (CDCl3) δ: 2.01-2.10(2H, m), 2.17(1H, dt, J=12.8, 8.3 Hz), 2.24-2.39(2H, m), 2.49(1H, ddd, J=12.8, 7.4, 3.8 Hz), 2.83-3.01(2H, m), 2.93(1H, d, J=15.9 Hz), 3.06(1H, d, J=15.9 Hz), 4.02(2H, t, J=6.0 Hz), 5.12(2H, s), 5.37(1H, s), 6.78(1H, s), 6.79(1H, d, J=7.5 Hz), 7.29(1H, d, J=7.5 Hz), 7.39(1H, t, J=7.3 Hz), 7.51(2H, t, J=7.8 Hz), 7.57(2H, d, J=7.5 Hz).
工程２
化合物２（４４．９ｍｇ、９８．４μｍｏｌ）、２－メタンスルホニル酢酸（５４ｍｇ、０．４０ｍｍｏｌ）、およびＮ、Ｎ－ジシクロヘキシルカルボジイミド（８２ｍｇ、０．４０ｍｍｏｌ）をジクロロメタン（２ｍＬ）に懸濁し、室温にて２５時間撹拌した。反応液にＮ、Ｎ－ジメチルアミノ－４－ピリジン（２．４ｍｇ、２０μｍｏｌ）を追加し、室温にてさらに４時間撹拌した。反応液に２－メタンスルホニル酢酸（２７ｍｇ、０．２０ｍｍｏｌ）およびＮ、Ｎ－ジシクロヘキシルカルボジイミド（４１ｍｇ、０．２０ｍｍｏｌ）を追加し、室温にてさらに２４時間撹拌した。反応液をろ過し、ろ液の溶媒を減圧留去した。得られた残渣をシリカゲルクロマトグラフィー（クロロホルム－メタノール）により精製した。さらに得られた固体をジイソプロピルエーテルで洗浄し、化合物Ｉ－３４（３６．３ｍｇ、収率６４％）を得た。
1H-NMR (CDCl3) δ: 1.95-2.06(2H, m), 2.19-2.32(3H, m), 2.44-2.54(1H, m), 2.90(3H, s), 2.91-3.04(2H, m), 3.09(1H, d, J=15.8 Hz), 3.18(1H, d, J=15.8 Hz), 3.88-3.97(2H, m), 4.02(1H, d, J=14.3 Hz), 4.22(1H, d, J=14.3 Hz), 6.12(1H, s), 6.66-6.72(1H, m), 6.76-6.79(1H, m), 7.18(1H, d, J=8.3 Hz), 7.35-7.52(5H, m), 9.66(1H, s). Example 1

Process 1
Known compound 1 (WO2017069224A1) (54.7 mg, 0.142 mmol) was dissolved in tetrahydrofuran (1.1 mL), phenylhydrazine (28 μL, 0.28 mmol) was added under ice cooling, and the mixture was stirred for 20 minutes. DIEA (50 μL, 0.28 mmol) was added to the reaction solution under ice-cooling, and the mixture was stirred at room temperature for 3 hours and then at 70 ° C. for 1 hour. The solvent of the reaction solution was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (chloroform-methanol) to obtain Compound 2 (59.4 mg, yield 92%).
1H-NMR (CDCl3) δ: 2.01-2.10 (2H, m), 2.17 (1H, dt, J = 12.8, 8.3 Hz), 2.24-2.39 (2H, m), 2.49 (1H, ddd, J = 12.8, 7.4, 3.8 Hz), 2.83-3.01 (2H, m), 2.93 (1H, d, J = 15.9 Hz), 3.06 (1H, d, J = 15.9 Hz), 4.02 (2H, t, J = 6.0 Hz) , 5.12 (2H, s), 5.37 (1H, s), 6.78 (1H, s), 6.79 (1H, d, J = 7.5 Hz), 7.29 (1H, d, J = 7.5 Hz), 7.39 (1H, s) t, J = 7.3 Hz), 7.51 (2H, t, J = 7.8 Hz), 7.57 (2H, d, J = 7.5 Hz).
Step 2
Compound 2 (44.9 mg, 98.4 μmol), 2-methanesulfonylacetic acid (54 mg, 0.40 mmol), and N, N-dicyclohexylcarbodiimide (82 mg, 0.40 mmol) were suspended in dichloromethane (2 mL) and brought to room temperature. And stirred for 25 hours. N, N-dimethylamino-4-pyridine (2.4 mg, 20 μmol) was added to the reaction mixture, and the mixture was further stirred at room temperature for 4 hours. 2-Methanesulfonylacetic acid (27 mg, 0.20 mmol) and N, N-dicyclohexylcarbodiimide (41 mg, 0.20 mmol) were added to the reaction mixture, and the mixture was further stirred at room temperature for 24 hours. The reaction solution was filtered, and the solvent of the filtrate was distilled off under reduced pressure. The obtained residue was purified by silica gel chromatography (chloroform-methanol). Further, the obtained solid was washed with diisopropyl ether to obtain compound I-34 (36.3 mg, yield 64%).
1H-NMR (CDCl3) δ: 1.95-2.06 (2H, m), 2.19-2.32 (3H, m), 2.44-2.54 (1H, m), 2.90 (3H, s), 2.91-3.04 (2H, m) , 3.09 (1H, d, J = 15.8 Hz), 3.18 (1H, d, J = 15.8 Hz), 3.88-3.97 (2H, m), 4.02 (1H, d, J = 14.3 Hz), 4.22 (1H, 1H, d, J = 14.3 Hz), 6.12 (1H, s), 6.66-6.72 (1H, m), 6.76-6.79 (1H, m), 7.18 (1H, d, J = 8.3 Hz), 7.35-7.52 (5H) , m), 9.66 (1H, s).

工程１
化合物１（１．０ｇ、２．６０ｍｍｏｌ）をエタノール（１５ｍＬ）に溶解し、ヒドラジン１水和物（０．６５ｍｌ、１３．０ｍｍｏｌ）を加え、室温から８０℃で１８時間撹拌した。室温下、反応液に重層水を加え、クロロホルムで抽出し、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、懸濁精製（酢酸エチル／ヘキサン）して化合物３（８９０ｍｇ、収率９０％）を得た。
1H-NMR (CDCl3) δ: 2.01-2.18(m, 3H), 2.25-2.42(m, 3H), 2.81-3.02(m, 4H), 4.00(t, J=5.9 Hz, 2H), 5.49(s, 1H), 6.75-6.77(m, 2H), 7.22(d, J=9.0 Hz, 1H).
工程２
化合物３の（１００ｍｇ、０．２４ｍｍｏｌ）をジクロロメタン（１．０ｍＬ）に溶解し、１－ブロモ－２－メトキシエタン（６６．７ｍｇ、０．４８ｍｍｏｌ）および炭酸セシウム（３１３ｍｇ、０．９６ｍｍｏｌ）を加え、９０℃で２時間撹拌した。室温下、反応液に水を加え、酢酸エチルで抽出し、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、化合物４を粗生成物として得た。
工程３
化合物４の粗生成物（０．２４ｍｍｏｌ）をトルエン（１ｍＬ）に溶解し、２－（メタンスルホニル）酢酸（６６．２ｍｇ、０．４８ｍｍｏｌ）およびＮ，Ｎ’－ジシクロヘキシルカルボジイミド（９９．０ｍｇ、０．４８ｍｍｏｌ）を室温で加え、１時間撹拌した。室温下、反応液に水を加え、酢酸エチルで抽出し、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）および逆相クロマトグラフィーにより精製して化合物Ｉ－５５（３０．０ｍｇ、２段階収率２２％）を得た。
1H-NMR (CDCl3) δ: 2.01-2.20(m, 3H), 2.25-2.44(m, 3H), 2.85-2.97(m, 3H), 3.09(d, J=15.8 Hz, 1H), 3.30(br-s, 3H), 3.39(s, 3H), 3.72(t, J=5.0 Hz, 2H), 3.99(t, J=5.9 Hz, 2H), 4.13(br-s, 2H), 4.28(br-s, 2H), 5.68(s, 1H), 6.77(br-s, 2H), 7.20-7.22(m, 1H). Example 2

Process 1
Compound 1 (1.0 g, 2.60 mmol) was dissolved in ethanol (15 mL), hydrazine monohydrate (0.65 ml, 13.0 mmol) was added, and the mixture was stirred at 80 ° C. for 18 hours from room temperature. At room temperature, layered water was added to the reaction solution, the mixture was extracted with chloroform, and dried over sodium sulfate. The solvent was distilled off under reduced pressure, and suspension purification (ethyl acetate / hexane) was performed to obtain Compound 3 (890 mg, yield 90%).
1H-NMR (CDCl3) δ: 2.01-2.18 (m, 3H), 2.25-2.42 (m, 3H), 2.81-3.02 (m, 4H), 4.00 (t, J = 5.9 Hz, 2H), 5.49 (s) , 1H), 6.75-6.77 (m, 2H), 7.22 (d, J = 9.0 Hz, 1H).
Step 2
Dissolve (100 mg, 0.24 mmol) of compound 3 in dichloromethane (1.0 mL) and add 1-bromo-2-methoxyethane (66.7 mg, 0.48 mmol) and cesium carbonate (313 mg, 0.96 mmol). , 90 ° C. for 2 hours. At room temperature, water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and dried over sodium sulfate. The solvent was evaporated under reduced pressure to give compound 4 as a crude product.
Process 3
The crude product of compound 4 (0.24 mmol) was dissolved in toluene (1 mL) with 2- (methanesulfonyl) acetic acid (66.2 mg, 0.48 mmol) and N, N'-dicyclohexylcarbodiimide (99.0 mg, 0). .48 mmol) was added at room temperature and stirred for 1 hour. At room temperature, water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) and reverse phase chromatography to obtain compound I-55 (30.0 mg, 2-step yield 22%). ..
1H-NMR (CDCl3) δ: 2.01-2.20 (m, 3H), 2.25-2.44 (m, 3H), 2.85-2.97 (m, 3H), 3.09 (d, J = 15.8 Hz, 1H), 3.30 (br -s, 3H), 3.39 (s, 3H), 3.72 (t, J = 5.0 Hz, 2H), 3.99 (t, J = 5.9 Hz, 2H), 4.13 (br-s, 2H), 4.28 (br- s, 2H), 5.68 (s, 1H), 6.77 (br-s, 2H), 7.20-7.22 (m, 1H).

工程１
化合物３の（７１９ｍｇ、１．８９ｍｍｏｌ）をＤＭＦ（７ｍＬ）に溶解し、２－シクロプロピルエチルメタンスルホナート（４６６ｍｇ、２．８４ｍｍｏｌ）および炭酸カリウム（１．３１ｇ、９．４５ｍｍｏｌ）を加え、８０℃で５時間撹拌した。室温下、反応液に水を加え、クロロホルムで抽出し、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をカラムクロマトグラフィー（酢酸エチル）により精製し、化合物５（３５８ｍｇ、収率４２％）を得た。
1H-NMR (CDCl3) δ: 0.06-0.10(m, 2H), 0.46-0.51(m, 2H), 0.63-0.72(m, 1H), 1.69-1.75(m, 2H), 2.03-2.15(dt, J=30.7, 9.3 Hz, 3H), 2.28-2.43(m, 3H), 2.82-3.00(m, 4H), 3.93-4.02(m, 4H), 4.78(br-s, 2H), 5.23(s, 1H), 6.76-9.78(m, 2H), 7.23-7.25(m, 1H).
工程２
化合物５（２．３０ｇ、５．１３ｍｍｏｌ）および二塩化銅（１．３８ｇ、１０．３ｍｍｏｌ）を、酢酸（７ｍＬ）および濃塩酸（１１ｍＬ）に溶解し、亜硝酸ナトリウム（４６０ｍｇ、６．６７ｍｍｏｌ）の水溶液（１ｍＬ）を氷冷下で滴下し、氷冷下にて４５分間撹拌した。反応液をクロロホルムで抽出し、有機層を飽和塩化アンモニウム水溶液と２Ｍ炭酸ナトリウム水溶液で洗浄した後、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をカラムクロマトグラフィー（クロロホルム－酢酸エチル）により精製し、化合物６（１．２４ｇ、収率５２％）を得た。
1H-NMR (CDCl3) δ: -0.04-0.05(2H, m), 0.40-0.51(2H, m), 0.61-0.72(1H, m), 1.69-1.82(2H, m), 2.01-2.10(2H, m), 2.14(1H, dt, J=13.1, 8.3 Hz), 2.25-2.42(3H, m), 2.82-3.00(2H, m), 2.94(1H, d, J=15.8 Hz), 3.08(1H, d, J=15.8 Hz), 4.01(2H, t, J=5.9 Hz), 4.24(2H, t, J=7.0 Hz), 5.59(1H, s), 6.76-6.80(2H, m), 7.22(1H, d, J=9.0 Hz).
工程３
化合物６（１．５７ｇ、３．３６ｍｍｏｌ）をＤＭＡ（１６ｍｌ）に溶解し、シアン化カリウム（６７８ｍｇ、１０．４ｍｍｏｌ）を加え、マイクロ波照射下、２００℃にて３時間撹拌した。反応液を室温に戻した後、飽和炭酸水素ナトリウム水溶液および水を加え、水層をヘキサン－酢酸エチル（２：１）で抽出した。有機層を水および飽和食塩水で洗浄した後、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、化合物７の粗生成物（１．４６ｇ）を得た。
工程４
化合物７の粗生成物（２１２ｍｇ）、アジ化ナトリウム(１５０ｍｇ、２．３１ｍｍｏｌ)および塩化アンモニウム(１２４ｍｇ、２．３１ｍｍｏｌ)を、ＤＭＦ（４．２ｍＬ）および水（０．４ｍＬ）に懸濁し、１４０℃にて３時間撹拌した。反応液を室温に戻した後、クエン酸水溶液を加え、水層を酢酸エチルで抽出した。有機層を硫酸ナトリウムで乾燥し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール）により精製して化合物Ｉ－２４（１６２ｍｇ、２段階収率６６％）を得た。
1H-NMR (CDCl3) δ: 0.01-0.06(2H, m), 0.36-0.42(2H, m), 0.73-0.82(1H, m), 1.88(2H, q, J=7.1 Hz), 2.02-2.11(2H, m), 2.18(1H, s), 2.20(1H, dt, J=13.3, 8.2 Hz), 2.26-2.39(2H, m), 2.45(1H, ddd, J=13.0, 7.7, 4.5 Hz), 2.88-3.06(2H, m), 3.12(1H, d, J=15.9 Hz), 3.22(1H, d, J=15.9 Hz), 4.03 (2H, t, J=6.0 Hz), 4.99-5.13(2H, m), 5.97(1H, s), 6.79-6.83(2H, m), 7.24(1H, d, J=9.3 Hz). Example 3

Process 1
Compound 3 (719 mg, 1.89 mmol) is dissolved in DMF (7 mL), 2-cyclopropylethylmethanesulfonate (466 mg, 2.84 mmol) and potassium carbonate (1.31 g, 9.45 mmol) are added, and 80 The mixture was stirred at ° C. for 5 hours. At room temperature, water was added to the reaction solution, the mixture was extracted with chloroform, and dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (ethyl acetate) to obtain Compound 5 (358 mg, yield 42%).
1H-NMR (CDCl3) δ: 0.06-0.10 (m, 2H), 0.46-0.51 (m, 2H), 0.63-0.72 (m, 1H), 1.69-1.75 (m, 2H), 2.03-2.15 (dt, J = 30.7, 9.3 Hz, 3H), 2.28-2.43 (m, 3H), 2.82-3.00 (m, 4H), 3.93-4.02 (m, 4H), 4.78 (br-s, 2H), 5.23 (s, 1H), 6.76-9.78 (m, 2H), 7.23-7.25 (m, 1H).
Step 2
Compound 5 (2.30 g, 5.13 mmol) and copper dichloride (1.38 g, 10.3 mmol) were dissolved in acetic acid (7 mL) and concentrated hydrochloric acid (11 mL) and sodium nitrite (460 mg, 6.67 mmol). The aqueous solution (1 mL) of the above solution was added dropwise under ice-cooling, and the mixture was stirred under ice-cooling for 45 minutes. The reaction mixture was extracted with chloroform, the organic layer was washed with saturated aqueous ammonium chloride solution and 2M aqueous sodium carbonate solution, and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by column chromatography (chloroform-ethyl acetate) to obtain Compound 6 (1.24 g, yield 52%).
1H-NMR (CDCl3) δ: -0.04-0.05 (2H, m), 0.40-0.51 (2H, m), 0.61-0.72 (1H, m), 1.69-1.82 (2H, m), 2.01-2.10 (2H) , m), 2.14 (1H, dt, J = 13.1, 8.3 Hz), 2.25-2.42 (3H, m), 2.82-3.00 (2H, m), 2.94 (1H, d, J = 15.8 Hz), 3.08 ( 1H, d, J = 15.8 Hz), 4.01 (2H, t, J = 5.9 Hz), 4.24 (2H, t, J = 7.0 Hz), 5.59 (1H, s), 6.76-6.80 (2H, m), 7.22 (1H, d, J = 9.0 Hz).
Process 3
Compound 6 (1.57 g, 3.36 mmol) was dissolved in DMA (16 ml), potassium cyanide (678 mg, 10.4 mmol) was added, and the mixture was stirred at 200 ° C. for 3 hours under microwave irradiation. After returning the reaction solution to room temperature, saturated aqueous sodium hydrogen carbonate solution and water were added, and the aqueous layer was extracted with hexane-ethyl acetate (2: 1). The organic layer was washed with water and saturated brine, and then dried over sodium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of compound 7 (1.46 g).
Step 4
The crude product of compound 7 (212 mg), sodium azide (150 mg, 2.31 mmol) and ammonium chloride (124 mg, 2.31 mmol) were suspended in DMF (4.2 mL) and water (0.4 mL), 140. The mixture was stirred at ° C. for 3 hours. After returning the reaction solution to room temperature, an aqueous citric acid solution was added, and the aqueous layer was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain Compound I-24 (162 mg, 2-step yield 66%).
1H-NMR (CDCl3) δ: 0.01-0.06 (2H, m), 0.36-0.42 (2H, m), 0.73-0.82 (1H, m), 1.88 (2H, q, J = 7.1 Hz), 2.02-2.11 (2H, m), 2.18 (1H, s), 2.20 (1H, dt, J = 13.3, 8.2 Hz), 2.26-2.39 (2H, m), 2.45 (1H, ddd, J = 13.0, 7.7, 4.5 Hz) ), 2.88-3.06 (2H, m), 3.12 (1H, d, J = 15.9 Hz), 3.22 (1H, d, J = 15.9 Hz), 4.03 (2H, t, J = 6.0 Hz), 4.99-5.13 (2H, m), 5.97 (1H, s), 6.79-6.83 (2H, m), 7.24 (1H, d, J = 9.3 Hz).

工程１
化合物７（１．４６ｇ、３．１８ｍｍｏｌ）をテトヒドロフラン（６ｍＬ）およびメタノール（６ｍＬ）に溶解し、５Ｎ水酸化ナトリウム水溶液（６．４ｍＬ、３．２ｍｍｏｌ）を加え、マイクロ波照射下、１２０℃にて７５分間撹拌した。反応液を室温に戻した後、２Ｎ塩酸（３０ｍＬ）を加え、水層をクロロホルムで抽出し、有機層を硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム－メタノール）により精製して、化合物２（１．１２ｇ、収率７３％）を得た。
1H-NMR (CDCl3) δ: -0.02-0.02(2H, m), 0.39-0.45(2H, m), 0.69-0.77(1H, m), 1.78(2H, q, J=7.2 Hz), 2.02-2.11(2H, m), 2.21(1H, dt, J=13.2, 8.2 Hz), 2.26-2.39(2H, m), 2.45(1H, ddd, J=13.0, 7.7, 4.5 Hz), 2.93(1H, dt, J=16.2, 7.7 Hz), 3.01(1H, ddd, J=16.5, 8.6, 4.3 Hz), 3.09(1H, d, J = 16.2 Hz), 3.19(1H, d, J=16.1 Hz), 4.03(2H, t, J=6.0 Hz), 4.76-4.89(2H, m), 6.01(1H, s), 6.79-6.84(2H, m), 7.19-7.23(1H, m), 15.66(1H, s).
工程２
化合物２（４８６ｍｇ、１．０２ｍｍｏｌ）およびカルボニルジイミダゾール（４９５ｍｇ、３．０５ｍｍｏｌ）をテトラヒドロフラン（５ｍＬ）に溶解し、７０℃にて１００分間撹拌した。反応液を室温に戻した後、メタンスルホン酸アミド（４８４ｍｇ、５．０９ｍｍｏｌ）およびジアザビシクロウンデセン（０．７７ｍＬ、５．１ｍｍｏｌ）を加え、室温にて１４時間撹拌した。溶媒を減圧留去した後、残渣に２Ｎ塩酸（２０ｍＬ）を加え、水層をクロロホルムで抽出し、有機層を硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣を固体化（ジイソプロピルエーテル－クロロホルム）により精製して、化合物Ｉ－１２（２８１ｍｇ、収率５０％）を得た。
1H-NMR (CDCl3) δ: 0.00-0.04(2H, m), 0.41-0.47(2H, m), 0.67-0.76(1H, m), 1.78(2H, qd, J=7.2, 1.4 Hz), 2.02-2.11(2H, m), 2.18(1H, dt, J=13.2, 8.2 Hz), 2.26-2.36(2H, m), 2.40(1H, ddd, J=13.1, 7.7, 4.4 Hz), 2.91(1H, dt, J=16.4, 8.1 Hz), 2.99(1H, ddd, J=16.5, 8.6, 4.5 Hz), 3.07(1H, d, J=15.8 Hz), 3.18(1H, d, J=15.8 Hz), 3.38(3H, s), 4.02(2H, t, J=6.0 Hz), 4.75-4.87(2H, m), 5.95(1H, s), 6.79-6.83(2H, m), 7.20-7.23(1H, m), 14.99(1H, s). Example 4

Process 1
Compound 7 (1.46 g, 3.18 mmol) was dissolved in tethydrofuran (6 mL) and methanol (6 mL), 5N aqueous sodium hydroxide solution (6.4 mL, 3.2 mmol) was added, and the mixture was exposed to microwaves to 120. The mixture was stirred at ° C for 75 minutes. After returning the reaction solution to room temperature, 2N hydrochloric acid (30 mL) was added, the aqueous layer was extracted with chloroform, and the organic layer was dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain Compound 2 (1.12 g, yield 73%).
1H-NMR (CDCl3) δ: -0.02-0.02 (2H, m), 0.39-0.45 (2H, m), 0.69-0.77 (1H, m), 1.78 (2H, q, J = 7.2 Hz), 2.02- 2.11 (2H, m), 2.21 (1H, dt, J = 13.2, 8.2 Hz), 2.26-2.39 (2H, m), 2.45 (1H, ddd, J = 13.0, 7.7, 4.5 Hz), 2.93 (1H, dt, J = 16.2, 7.7 Hz), 3.01 (1H, ddd, J = 16.5, 8.6, 4.3 Hz), 3.09 (1H, d, J = 16.2 Hz), 3.19 (1H, d, J = 16.1 Hz), 4.03 (2H, t, J = 6.0 Hz), 4.76-4.89 (2H, m), 6.01 (1H, s), 6.79-6.84 (2H, m), 7.19-7.23 (1H, m), 15.66 (1H, m) s).
Step 2
Compound 2 (486 mg, 1.02 mmol) and carbonyldiimidazole (495 mg, 3.05 mmol) were dissolved in tetrahydrofuran (5 mL) and stirred at 70 ° C. for 100 minutes. After returning the reaction solution to room temperature, methanesulfonic acid amide (484 mg, 5.09 mmol) and diazabicycloundecene (0.77 mL, 5.1 mmol) were added, and the mixture was stirred at room temperature for 14 hours. After distilling off the solvent under reduced pressure, 2N hydrochloric acid (20 mL) was added to the residue, the aqueous layer was extracted with chloroform, and the organic layer was dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by solidification (diisopropyl ether-chloroform) to obtain Compound I-12 (281 mg, yield 50%).
1H-NMR (CDCl3) δ: 0.00-0.04 (2H, m), 0.41-0.47 (2H, m), 0.67-0.76 (1H, m), 1.78 (2H, qd, J = 7.2, 1.4 Hz), 2.02 -2.11 (2H, m), 2.18 (1H, dt, J = 13.2, 8.2 Hz), 2.26-2.36 (2H, m), 2.40 (1H, ddd, J = 13.1, 7.7, 4.4 Hz), 2.91 (1H) , dt, J = 16.4, 8.1 Hz), 2.99 (1H, ddd, J = 16.5, 8.6, 4.5 Hz), 3.07 (1H, d, J = 15.8 Hz), 3.18 (1H, d, J = 15.8 Hz) , 3.38 (3H, s), 4.02 (2H, t, J = 6.0 Hz), 4.75-4.87 (2H, m), 5.95 (1H, s), 6.79-6.83 (2H, m), 7.20-7.23 (1H) , m), 14.99 (1H, s).

工程１
化合物７（２３．１ｍｇ、５０．４μｍｏｌ）および５％パラジウム炭素（２３ｍｇ）を、メタノール（１．５ｍＬ）および濃塩酸（０．２ｍＬ）に懸濁し、水素雰囲気下、室温にて４時間撹拌した。反応液をろ過した後、溶媒を減圧留去し、化合物９（２４．９ｍｇ、収率９９％）を得た。
1H-NMR (DMSO-D6) δ: -0.08-0.04(2H, m), 0.34-0.41(2H, m), 0.58-0.67(1H, m), 1.59-1.67(2H, m), 1.91(2H, dt, J=15.6, 6.4 Hz), 2.14-2.28(2H, m), 2.36-2.45(2H, m), 2.90(2H, t, J=6.7 Hz), 2.94(1H, d, J=15.8 Hz), 3.01(1H, d, J = 15.8 Hz), 4.01(2H, t, J=6.1 Hz), 4.22(2H, t, J=6.7 Hz), 4.38(1H, d, J=15.2 Hz), 4.43(1H, d, J=15.2 Hz), 6.68(1H, dd, J=8.4, 2.3 Hz), 6.85(1H, d, J=2.3 Hz), 7.01(1H, d, J=8.4 Hz), 8.42(1H, s), 8.73(3H, s).
工程２
化合物９（６．０ｍｇ、１２μｍｏｌ）をテトラヒドロフラン（０．７ｍＬ）に懸濁し、無水酢酸（６μＬ、０．０６ｍｍｏｌ）およびトリエチルアミン（１７μＬ、０．１２ｍｍｏｌ）を加え、室温にて２０分間撹拌した。メタノール（２ｍＬ）を加えた後、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム－メタノール）により精製して、化合物Ｉ－１０（４．６ｍｇ、収率７６％）を得た。
1H-NMR (CDCl3) δ: -0.05-0.05(2H, m), 0.39-0.48(2H, m), 0.60-0.72(1H, m), 1.75(2H, q, J=7.0 Hz), 2.02(3H, s), 2.03-2.10(2H, m), 2.14(1H, dt, J=13.1, 8.0 Hz), 2.25-2.36(2H, m), 2.40(1H, ddd, J=12.9, 7.7, 4.2 Hz), 2.83-2.97(2H, m), 2.96(1H, d, J=15.8 Hz), 3.07(1H, d, J=15.8 Hz), 4.02(2H, t, J=6.0 Hz), 4.27(2H, t, J=7.2 Hz), 4.55(1H, dd, J=16.1, 4.8 Hz), 4.76(1H, dd, J=16.1, 6.0 Hz), 5.73(1H, s), 6.76-6.81(2H, m), 7.19-7.24(1H, m), 8.65-8.72(1H, m). Example 5

Process 1
Compound 7 (23.1 mg, 50.4 μmol) and 5% palladium carbon (23 mg) were suspended in methanol (1.5 mL) and concentrated hydrochloric acid (0.2 mL), and the mixture was stirred at room temperature for 4 hours under a hydrogen atmosphere. .. After filtering the reaction solution, the solvent was distilled off under reduced pressure to obtain Compound 9 (24.9 mg, yield 99%).
1H-NMR (DMSO-D6) δ: -0.08-0.04 (2H, m), 0.34-0.41 (2H, m), 0.58-0.67 (1H, m), 1.59-1.67 (2H, m), 1.91 (2H) , dt, J = 15.6, 6.4 Hz), 2.14-2.28 (2H, m), 2.36-2.45 (2H, m), 2.90 (2H, t, J = 6.7 Hz), 2.94 (1H, d, J = 15.8) Hz), 3.01 (1H, d, J = 15.8 Hz), 4.01 (2H, t, J = 6.1 Hz), 4.22 (2H, t, J = 6.7 Hz), 4.38 (1H, d, J = 15.2 Hz) , 4.43 (1H, d, J = 15.2 Hz), 6.68 (1H, dd, J = 8.4, 2.3 Hz), 6.85 (1H, d, J = 2.3 Hz), 7.01 (1H, d, J = 8.4 Hz) , 8.42 (1H, s), 8.73 (3H, s).
Step 2
Compound 9 (6.0 mg, 12 μmol) was suspended in tetrahydrofuran (0.7 mL), acetic anhydride (6 μL, 0.06 mmol) and triethylamine (17 μL, 0.12 mmol) were added, and the mixture was stirred at room temperature for 20 minutes. After adding methanol (2 mL), the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain Compound I-10 (4.6 mg, yield 76%).
1H-NMR (CDCl3) δ: -0.05-0.05 (2H, m), 0.39-0.48 (2H, m), 0.60-0.72 (1H, m), 1.75 (2H, q, J = 7.0 Hz), 2.02 ( 3H, s), 2.03-2.10 (2H, m), 2.14 (1H, dt, J = 13.1, 8.0 Hz), 2.25-2.36 (2H, m), 2.40 (1H, ddd, J = 12.9, 7.7, 4.2 Hz), 2.83-2.97 (2H, m), 2.96 (1H, d, J = 15.8 Hz), 3.07 (1H, d, J = 15.8 Hz), 4.02 (2H, t, J = 6.0 Hz), 4.27 ( 2H, t, J = 7.2 Hz), 4.55 (1H, dd, J = 16.1, 4.8 Hz), 4.76 (1H, dd, J = 16.1, 6.0 Hz), 5.73 (1H, s), 6.76-6.81 (2H) , m), 7.19-7.24 (1H, m), 8.65-8.72 (1H, m).

工程１
既知化合物１０（WO2017069224A1）（１０００ｍｇ、３．１３ｍｍｏｌ）をジクロロエタン（１０ｍＬ）に溶解し、塩化ホスホリル（０．５２４ｍＬ、５．６４ｍｍｏｌ）のジクロロエタン溶液（２．５ｍＬ）を加え、２０分間攪拌した。反応液にＤＭＦ（０．４３４ｍＬ、５．６４ｍｍｏｌ）を加え、３時間撹拌した。反応液に炭酸水素ナトリウム水溶液を加えた後、酢酸エチルで抽出した。有機層を水で洗浄した後、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣を懸濁精製（ヘキサン‐酢酸エチル）により精製して化合物１１（７２０ｍｇ、収率６８％）を得た。
［Ｍ＋Ｈ］＝３３６．９０、測定条件Ｃ
工程２
化合物１１（３５０ｍｇ、１．０４ｍｍｏｌ）をイソプロパノール（３．５ｍＬ）に溶解し、化合物１２（２７０ｍｇ、１．３５ｍｍｏｌ）および炭酸水素ナトリウム（１３１ｍｇ、１．５５ｍｍｏｌ）を加え、９０℃で６時間撹拌した。溶液を濾過し、溶媒を減圧留去した。得られた残渣に１０ｗｔ％塩酸－メタノール（３．５５ｇ、５．１８ｍｍｏｌ）を加え、１４時間撹拌した。反応液に炭酸水素ナトリウム水溶液を加えた後、酢酸エチルで抽出した。有機層を水で洗浄した後、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール）により精製して化合物１３（３６０ｍｇ、収率８７％）を得た。
［Ｍ＋Ｈ］＝４０１．００、測定条件Ｃ
工程３
化合物１３（１００ｍｇ、０．２４９ｍｍｏｌ）をジオキサン（３ｍＬ）に溶解し、4,4,4',4',5,5,5',5'-オクタメチル-2,2'-ビ-1,3,2-ジオキサボロラン（８２ｍｇ、０．３２４ｍｍｏｌ）、[1,1'-ビス(ジフェニルホスフィノ)フェロセン]パラジウム(II)ジクロリド ジクロロメタン付加物（２０ｍｇ、０．０２５ｍｍｏｌ）および酢酸カリウム（６８ｍｇ、０．６９８ｍｍｏｌ）を加え、９５℃で１時間撹拌した。反応液に３０％過酸化水素水溶液（２８３ｍＬ、２．４９ｍｍｏｌ）を氷冷下加え、室温で２時間撹拌した。反応液にチオ硫酸ナトリウム水溶液を加え、酢酸エチルで抽出した後、有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール）により精製して、化合物１４（７５ｍｇ、収率８９％）を得た。
［Ｍ＋Ｈ］＝３３９．０５、測定条件Ｃ
工程４
化合物１４（７５ｍｇ、０．２２２ｍｍｏｌ）をＤＭＦ（１ｍＬ）に溶解し、炭酸カリウム（３０６ｍｇ、２．２１６ｍｍｏｌ）およびトリフルオロメタンスルホン酸2,2,2-トリフルオロエチル（０．０９６ｍＬ、０．６６５ｍｍｏｌ）を加え、３時間撹拌した。反応液に水を加え、酢酸エチルで抽出した後、有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）により精製して、化合物１５（９３ｍｇ、収率１００％）を得た。
［Ｍ＋Ｈ］＝４２１．１０、測定条件Ｃ
工程５
化合物１５（９３ｍｇ、０．２２１ｍｍｏｌ）をジクロロメタン（１ｍＬ）に溶解し、２－メチルスルホニル酢酸（６１ｍｇ、０．４４２ｍｍｏｌ）およびジシクロヘキシルカルボジイミド（９１ｍｇ、０．４４２ｍｍｏｌ）を加え、１時間撹拌した。反応液に水を加え、酢酸エチルで抽出した後、有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）により精製し、超臨界クロマトグラフィー（エタノール）により光学分割し、化合物Ｉ－２８２およびＩ－２８３（２１ｍｇ、収率３５％）を得た。
分析条件
＜Waters製 SFC30システム＞
カラム：CHIRALPAK IB/SFC （5μｍ、ｉ．ｄ．250ｘ4.6ｍｍ） （DAICEL）
流速：2.0 ｍＬ／分；ＵＶ検出波長：220ｎｍ
背圧：15Mpa
移動相：［Ａ］液化炭酸、［Ｂ］エタノール
７０％溶媒［Ｂ］を１５分間維持した。
溶出時間：Ｉ-283 4.1分, I-282 4.7分
I-282：［Ｍ＋Ｈ］＝５４１、測定条件Ｂ、保持時間１．９４分
I-283：¹H-NMR (CDCl₃) δ: 0.01-0.02 (m, 2H), 0.39-0.44 (m, 2H), 1.77 (q, J = 7.2 Hz, 2H), 3.02-3.10 (m, 6H), 3.23 (s, 3H), 4.08 (t, J = 7.3 Hz, 2H), 4.27-4.31 (m, 4H), 6.19 (s, 1H), 6.73-6.76 (m, 2H), 7.11 (d, J = 8.2 Hz, 1H), 9.67 (s, 1H).
なお、化合物Ｉ－２８２およびＩ－２８３はそれぞれ光学活性体であるが、立体配置は決定していない。 Example 6

Process 1
Known compound 10 (WO2017069224A1) (1000 mg, 3.13 mmol) was dissolved in dichloroethane (10 mL), phosphoryl chloride (0.524 mL, 5.64 mmol) in dichloroethane solution (2.5 mL) was added, and the mixture was stirred for 20 minutes. DMF (0.434 mL, 5.64 mmol) was added to the reaction mixture, and the mixture was stirred for 3 hours. After adding an aqueous sodium hydrogen carbonate solution to the reaction solution, the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by suspension purification (hexane-ethyl acetate) to obtain Compound 11 (720 mg, yield 68%).
[M + H] = 336.90, measurement condition C
Step 2
Compound 11 (350 mg, 1.04 mmol) was dissolved in isopropanol (3.5 mL), compound 12 (270 mg, 1.35 mmol) and sodium hydrogen carbonate (131 mg, 1.55 mmol) were added, and the mixture was stirred at 90 ° C. for 6 hours. .. The solution was filtered and the solvent was distilled off under reduced pressure. 10 wt% hydrochloric acid-methanol (3.55 g, 5.18 mmol) was added to the obtained residue, and the mixture was stirred for 14 hours. After adding an aqueous sodium hydrogen carbonate solution to the reaction solution, the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain compound 13 (360 mg, yield 87%).
[M + H] = 401.00, measurement condition C
Process 3
Compound 13 (100 mg, 0.249 mmol) was dissolved in dioxane (3 mL) and 4,4,4', 4', 5,5,5', 5'-octamethyl-2,2'-bi-1,3 , 2-Dioxaborolane (82 mg, 0.324 mmol), [1,1'-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane adduct (20 mg, 0.025 mmol) and potassium acetate (68 mg, 0.698 mmol). ) Was added, and the mixture was stirred at 95 ° C. for 1 hour. A 30% aqueous hydrogen peroxide solution (283 mL, 2.49 mmol) was added to the reaction solution under ice-cooling, and the mixture was stirred at room temperature for 2 hours. An aqueous sodium thiosulfate solution was added to the reaction mixture, the mixture was extracted with ethyl acetate, the organic layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain Compound 14 (75 mg, yield 89%).
[M + H] = 339.05, measurement condition C
Step 4
Compound 14 (75 mg, 0.222 mmol) was dissolved in DMF (1 mL) and potassium carbonate (306 mg, 2.216 mmol) and trifluoromethanesulfonic acid 2,2,2-trifluoroethyl (0.096 mL, 0.665 mmol). Was added, and the mixture was stirred for 3 hours. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, the organic layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 15 (93 mg, 100% yield).
[M + H] = 421.10, measurement condition C
Step 5
Compound 15 (93 mg, 0.221 mmol) was dissolved in dichloromethane (1 mL), 2-methylsulfonylacetic acid (61 mg, 0.442 mmol) and dicyclohexylcarbodiimide (91 mg, 0.442 mmol) were added, and the mixture was stirred for 1 hour. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, the organic layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) and optically resolved by supercritical chromatography (ethanol) to obtain compounds I-282 and I-283 (21 mg, collected). Rate 35%) was obtained.
Analytical conditions <Waters SFC30 system>
Column: CHIRALPAK IB / SFC (5 μm, id. 250 x 4.6 mm) (DAICEL)
Flow velocity: 2.0 mL / min; UV detection wavelength: 220 nm
Back pressure: 15Mpa
Mobile phase: [A] liquefied carbonic acid, [B] ethanol 70% solvent [B] was maintained for 15 minutes.
Elution time: I-283 4.1 minutes, I-282 4.7 minutes
I-282: [M + H] = 541, measurement condition B, holding time 1.94 minutes
I-283: ¹ H-NMR (CDCl ₃ ) δ: 0.01-0.02 (m, 2H), 0.39-0.44 (m, 2H), 1.77 (q, J = 7.2 Hz, 2H), 3.02-3.10 (m, 6H), 3.23 (s, 3H), 4.08 (t, J = 7.3 Hz, 2H), 4.27-4.31 (m, 4H), 6.19 (s, 1H), 6.73-6.76 (m, 2H), 7.11 (d) , J = 8.2 Hz, 1H), 9.67 (s, 1H).
Although compounds I-282 and I-283 are optically active substances, their stereoscopic arrangements have not been determined.

工程１
化合物１６（１５０ｍｇ、０．４４ｍｍｏｌ）をエタノール（１ｍＬ）に溶解し、化合物１７（１３２ｍｇ、０．８９ｍｍｏｌ）およびＤＢＵ（０．６７ｍｌ、４．４４ｍｍｏｌ）を室温で加え、１００℃で３０分撹拌した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して、化合物１８（６０ｍｇ、収率３３％）を得た。
¹H-NMR (CDCl₃) δ: 0.04-0.08(m, 2H), 0.39-0.44(m, 2H), 0.72-0.81(m, 1H), 1.67(dd, J=15.4, 7.2 Hz, 2H), 2.05-2.17(m, 1H), 2.39-2.45(m, 1H), 2.78-2.82(m, 2H), 2.93-3.00(m, 3H), 3.14(d, J = 16.3 Hz, 1H), 5.57(s, 1H), 5.79(s, 1H), 7.16(d, J=8.3 Hz, 1H), 7.34-7.42(m, 2H), 8.43(s, 1H).
工程２
実施例６の工程３に従い、化合物１９（４５ｍｇ、９２％）を得た。
［Ｍ＋Ｈ］＝３５１．０５、測定条件Ｃ
工程３
実施例６の工程４に従い、化合物２０の粗生成物を得た。
工程４
化合物５の粗生成物（０．０５３ｍｍｏｌ）をジクロロメタン（１ｍＬ）に溶解し、２－（メタンスルホニル）アセチルクロライド（０．４８ｍｍｏｌ）およびピリジン（０．０６３ｍｌ、０．８１ｍｍｏｌ）を０℃で加え、３時間撹拌した。室温下、水を加え、酢酸エチルで抽出し、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）および逆相クロマトグラフィーとプレパラティブＴＬＣにより精製して化合物Ｉ－２７７（２．２ｍｇ、２段階収率８％）を得た。
¹H-NMR (CDCl₃) δ: 0.05-0.09(m, 2H), 0.41-0.46(m, 2H), 0.72-0.81(m, 1H), 1.74(dd, J=15.2, 7.2 Hz, 2H), 2.16-2.23(m, 1H), 2.37-2.43(m, 1H), 2.92-3.04(m, 4H), 3.11(d, J=17.7 Hz, 1H), 3.30(d, J=16.8 Hz, 1H), 4.33-4.39(m, 2H), 4.93(d, J=14.3 Hz, 1H), 5.10(d, J=14.3 Hz, 1H), 6.30(s, 1H), 6.85-6.87(m, 2H), 7.21-7.23(m, 1H), 12.11(s, 1H). Example 7

Process 1
Compound 16 (150 mg, 0.44 mmol) was dissolved in ethanol (1 mL), compound 17 (132 mg, 0.89 mmol) and DBU (0.67 ml, 4.44 mmol) were added at room temperature, and the mixture was stirred at 100 ° C. for 30 minutes. .. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 18 (60 mg, yield 33%).
¹ H-NMR (CDCl ₃ ) δ: 0.04-0.08 (m, 2H), 0.39-0.44 (m, 2H), 0.72-0.81 (m, 1H), 1.67 (dd, J = 15.4, 7.2 Hz, 2H) , 2.05-2.17 (m, 1H), 2.39-2.45 (m, 1H), 2.78-2.82 (m, 2H), 2.93-3.00 (m, 3H), 3.14 (d, J = 16.3 Hz, 1H), 5.57 (s, 1H), 5.79 (s, 1H), 7.16 (d, J = 8.3 Hz, 1H), 7.34-7.42 (m, 2H), 8.43 (s, 1H).
Step 2
Compound 19 (45 mg, 92%) was obtained according to Step 3 of Example 6.
[M + H] = 351.05, measurement condition C
Process 3
A crude product of compound 20 was obtained according to step 4 of Example 6.
Step 4
The crude product of compound 5 (0.053 mmol) was dissolved in dichloromethane (1 mL) and 2- (methanesulfonyl) acetyl chloride (0.48 mmol) and pyridine (0.063 ml, 0.81 mmol) were added at 0 ° C. The mixture was stirred for 3 hours. At room temperature, water was added, the mixture was extracted with ethyl acetate, and dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate), reverse phase chromatography and preparative TLC to compound I-277 (2.2 mg, 2-step yield 8%). ) Was obtained.
¹ H-NMR (CDCl ₃ ) δ: 0.05-0.09 (m, 2H), 0.41-0.46 (m, 2H), 0.72-0.81 (m, 1H), 1.74 (dd, J = 15.2, 7.2 Hz, 2H) , 2.16-2.23 (m, 1H), 2.37-2.43 (m, 1H), 2.92-3.04 (m, 4H), 3.11 (d, J = 17.7 Hz, 1H), 3.30 (d, J = 16.8 Hz, 1H) ), 4.33-4.39 (m, 2H), 4.93 (d, J = 14.3 Hz, 1H), 5.10 (d, J = 14.3 Hz, 1H), 6.30 (s, 1H), 6.85-6.87 (m, 2H) , 7.21-7.23 (m, 1H), 12.11 (s, 1H).

工程１
既知化合物２１（WO2017069224A1）（３．０ｇ、７．７３ｍｍｏｌ）をテトラヒドロフラン（２０ｍＬ）およびメタノール（１０ｍＬ）の混合溶媒に溶解し、２Ｎ水酸化ナトリウム水溶液（４．６４ｍＬ、９．２７ｍｍｏｌ）を加え、２時間撹拌した。反応液に１Ｎ塩酸水溶液を加えた後、酢酸エチルで抽出した。有機層を水で洗浄した後、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣を固体化（ヘキサン‐酢酸エチル）により精製して化合物２２（２．７ｇ、収率９３％）を得た。
［Ｍ＋Ｈ］＝３７４．００、測定条件Ｃ
工程２
化合物２２（５００ｍｇ、１．３４ｍｍｏｌ）をアセトニトリル（５ｍＬ）に溶解し、2-クロロアセトフェノン（２１７ｍｇ、１．４０ｍｍｏｌ）および炭酸セシウム（６５３ｍｇ、２．００ｍｍｏｌ）を加え、１時間撹拌した。反応液に水を加えた後、酢酸エチルで抽出した。有機層を水で洗浄した後、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣を固体化（ヘキサン‐酢酸エチル）により精製して化合物２３（３３０ｍｇ、収率５０％）を得た。
［Ｍ＋Ｈ］＝４９２．００、測定条件Ｃ
工程３
化合物２３（３３０ｍｇ、０．６７０ｍｍｏｌ）をトルエン（５ｍＬ）に溶解し、酢酸アンモニウム（５１７ｍｇ、６．７０ｍｍｏｌ）を加え、１２０℃で４時間撹拌した。反応液に水を加えた後、酢酸エチルで抽出した。有機層を水で洗浄した後、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール）により精製して、化合物２４（２２０ｍｇ、収率７０％）を得た。
¹H-NMR (DMSO-D₆) δ: 1.17 (s, 9H), 2.14-2.17 (m, 1H), 2.35-2.41 (m, 1H), 2.82-2.88 (m, 2H), 2.96-3.00 (m, 1H), 3.12 (d, J = 14.4 Hz, 1H), 6.71 (s, 1H), 7.13-7.21 (m, 2H), 7.33-7.42 (m, 4H), 7.48 (s, 1H), 7.57 (s, 2H), 7.76 (d, J = 7.7 Hz, 2H).［Ｍ＋Ｈ］＝４７２．０５、測定条件Ｃ
工程４
化合物２４（１００ｍｇ、０．２１２ｍｍｏｌ）をメタノール（１ｍＬ）に溶解し、４Ｎ塩酸－ジオキサン溶液（１５９ｍＬ、０．６３５ｍｍｏｌ）を加え、１時間撹拌した。溶媒を減圧留去し、得られた残渣をジクロロメタン（１ｍＬ）に溶解し、ピリジン（０．０８５ｍＬ、１．０６ｍｍｏｌ）およびクロロギ酸４－ニトロフェニル（５８．９ｍｇ、０．３１７ｍｍｏｌ）を加え、３０分間撹拌した。反応液にトリエチルアミン（０．２９３ｍＬ、２．１２ｍｍｏｌ）を加え、２時間撹拌した。その後、水を加えた後、酢酸エチルで抽出した。有機層を水で洗浄した後、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）により精製して、化合物２５（６５ｍｇ、収率７８％）を得た。
¹H-NMR (DMSO-D₆) δ: 2.23-2.28(m, 2H), 2.99(t, J=6.9 Hz, 2H), 3.26(q, J=14.3 Hz, 2H), 6.92(d, J=8.3 Hz, 1H), 7.26(t, J=7.4 Hz, 1H), 7.38(t, J=7.5 Hz, 3H), 7.52(s, 1H), 7.86(d, J=7.0 Hz, 2H), 8.08(s, 1H), 8.82(s, 1H).
工程５
実施例６の工程３に従い、化合物２６と不純物の混合物（８０ｍｇ）を得た。
［Ｍ＋Ｈ］＝３３２．０５、測定条件Ｃ
工程６
実施例６の工程４に従い、化合物２７（４０ｍｇ、２段階収率６１％）を得た。
¹H-NMR (CDCl₃) δ: 2.23-2.27(m, 1H), 2.45-2.49(m, 1H), 2.90-3.01(m, 2H), 3.20-3.31(m, 2H), 4.36(q, J=8.1 Hz, 2H), 5.89(s, 1H), 6.83-7.21(m, 3H), 7.36-8.00(m, 5H).
工程７
化合物２７（４０ｍｇ、０．０９７ｍｍｏｌ）をジクロロメタン（３ｍＬ）に溶解し、N-ブロモスクシンイミド（３４ｍｇ、０．１９４ｍｍｏｌ）を氷冷下加え、室温で１時間撹拌した。反応液にチオ硫酸ナトリウム水溶液を加え、酢酸エチルで抽出した後、有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）により精製して、化合物２８（１２ｍｇ、２５％）を得た。
¹H-NMR (CDCl₃) δ: 2.23-2.27(m, 1H), 2.45-2.49(m, 1H), 2.90-3.01(m, 2H), 3.20-3.31(m, 2H), 4.36(q, J=8.1 Hz, 2H), 5.89(s, 1H), 6.83-7.21(m, 3H), 7.36-8.00(m, 5H).
工程８
化合物２８（５．０ｍｇ、０．０１０ｍｍｏｌ）をジオキサン（０．５ｍＬ）に溶解し、ジフェニルメタンイミン（９．２ｍｇ、０．０５１ｍｍｏｌ）、クロロ[(4,5-ビス(ジフェニルホスフィノ)-9,9-ジメチルキサンテン)-2-(2’-アミノ-1,1’ビフェニル)]パラジウム(II)（３．５ｍｇ、０．０１０ｍｍｏｌ）およびt-ブトキシナトリウム（２．７ｍｇ、０．０２８ｍｍｏｌ）を加え、マイクロウェーブ照射下、１４０℃で３０分間撹拌した。反応液に水を加え、酢酸エチルで抽出した後、有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）により精製して、化合物２９（４．０ｍｇ、６７％）を得た。
［Ｍ＋Ｈ］＝５９３．１５、測定条件Ｃ
工程９
化合物２９（４．０ｍｇ、０．００７ｍｍｏｌ）をテトラヒドロフラン（０．５ｍＬ）に溶解し、２Ｎ塩酸水溶液（０．１０ｍＬ、０．２０２ｍｍｏｌ）を加え、３時間撹拌した。溶媒を減圧留去し、得られた残渣をトルエン（０．５ｍＬ）に溶解した。その後、2-メチルスルホニル酢酸（４．８ｍｇ、０．０３５ｍｍｏｌ）およびジシクロヘキシルカルボジイミド（７．２ｍｇ、０．０３５ｍｍｏｌ）を加え、３０分間撹拌した。反応液に水を加え、酢酸エチルで抽出した後、有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣を逆相カラムクロマトグラフィーにより精製して、化合物Ｉ－２０１（１．０ｍｇ、２段階収率２６％）を得た。
¹H-NMR (CDCl₃) δ: 2.26-2.27(m, 1H), 2.44-2.51(m, 1H), 2.93-3.07(m, 2H), 3.15(s, 2H), 3.18-3.32(m, 2H), 3.93-4.18(m, 2H), 4.30-4.37(m, 2H), 5.59-5.87(m, 1H), 6.83-6.89(m, 2H), 7.19-7.20(m, 1H), 7.30-7.32(m, 1H), 7.38-7.43(m, 3H), 7.76(d, J=7.8 Hz, 1H), 8.19-8.79(m, 1H). Example 8

Process 1
Known compound 21 (WO2017069224A1) (3.0 g, 7.73 mmol) is dissolved in a mixed solvent of tetrahydrofuran (20 mL) and methanol (10 mL), 2N aqueous sodium hydroxide solution (4.64 mL, 9.27 mmol) is added, and 2 Stir for hours. A 1N aqueous hydrochloric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by solidification (hexane-ethyl acetate) to obtain compound 22 (2.7 g, yield 93%).
[M + H] = 374.00, measurement condition C
Step 2
Compound 22 (500 mg, 1.34 mmol) was dissolved in acetonitrile (5 mL), 2-chloroacetophenone (217 mg, 1.40 mmol) and cesium carbonate (653 mg, 2.00 mmol) were added, and the mixture was stirred for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by solidification (hexane-ethyl acetate) to obtain compound 23 (330 mg, yield 50%).
[M + H] = 492.00, measurement condition C
Process 3
Compound 23 (330 mg, 0.670 mmol) was dissolved in toluene (5 mL), ammonium acetate (517 mg, 6.70 mmol) was added, and the mixture was stirred at 120 ° C. for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain compound 24 (220 mg, yield 70%).
¹ H-NMR (DMSO-D ₆ ) δ: 1.17 (s, 9H), 2.14-2.17 (m, 1H), 2.35-2.41 (m, 1H), 2.82-2.88 (m, 2H), 2.96-3.00 ( m, 1H), 3.12 (d, J = 14.4 Hz, 1H), 6.71 (s, 1H), 7.13-7.21 (m, 2H), 7.33-7.42 (m, 4H), 7.48 (s, 1H), 7.57 (s, 2H), 7.76 (d, J = 7.7 Hz, 2H). [M + H] = 472.05, measurement condition C
Step 4
Compound 24 (100 mg, 0.212 mmol) was dissolved in methanol (1 mL), a 4N hydrochloric acid-dioxane solution (159 mL, 0.635 mmol) was added, and the mixture was stirred for 1 hour. The solvent was distilled off under reduced pressure, the obtained residue was dissolved in dichloromethane (1 mL), pyridine (0.085 mL, 1.06 mmol) and 4-nitrophenyl chloroformate (58.9 mg, 0.317 mmol) were added, and 30 Stir for minutes. Triethylamine (0.293 mL, 2.12 mmol) was added to the reaction mixture, and the mixture was stirred for 2 hours. Then, after adding water, it was extracted with ethyl acetate. The organic layer was washed with water and then dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 25 (65 mg, yield 78%).
¹ H-NMR (DMSO-D ₆ ) δ: 2.23-2.28 (m, 2H), 2.99 (t, J = 6.9 Hz, 2H), 3.26 (q, J = 14.3 Hz, 2H), 6.92 (d, J) = 8.3 Hz, 1H), 7.26 (t, J = 7.4 Hz, 1H), 7.38 (t, J = 7.5 Hz, 3H), 7.52 (s, 1H), 7.86 (d, J = 7.0 Hz, 2H), 8.08 (s, 1H), 8.82 (s, 1H).
Step 5
A mixture of compound 26 and impurities (80 mg) was obtained according to step 3 of Example 6.
[M + H] = 332.05, measurement condition C
Step 6
Compound 27 (40 mg, 2-step yield 61%) was obtained according to Step 4 of Example 6.
¹ H-NMR (CDCl ₃ ) δ: 2.23-2.27 (m, 1H), 2.45-2.49 (m, 1H), 2.90-3.01 (m, 2H), 3.20-3.31 (m, 2H), 4.36 (q, J = 8.1 Hz, 2H), 5.89 (s, 1H), 6.83-7.21 (m, 3H), 7.36-8.00 (m, 5H).
Step 7
Compound 27 (40 mg, 0.097 mmol) was dissolved in dichloromethane (3 mL), N-bromosuccinimide (34 mg, 0.194 mmol) was added under ice-cooling, and the mixture was stirred at room temperature for 1 hour. An aqueous sodium thiosulfate solution was added to the reaction mixture, the mixture was extracted with ethyl acetate, the organic layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 28 (12 mg, 25%).
¹ H-NMR (CDCl ₃ ) δ: 2.23-2.27 (m, 1H), 2.45-2.49 (m, 1H), 2.90-3.01 (m, 2H), 3.20-3.31 (m, 2H), 4.36 (q, J = 8.1 Hz, 2H), 5.89 (s, 1H), 6.83-7.21 (m, 3H), 7.36-8.00 (m, 5H).
Step 8
Compound 28 (5.0 mg, 0.010 mmol) was dissolved in dioxane (0.5 mL), diphenylmethaneimine (9.2 mg, 0.051 mmol), chloro [(4,5-bis (diphenylphosphino) -9, 9-Dimethylxanthene) -2- (2'-amino-1,1'biphenyl)] palladium (II) (3.5 mg, 0.010 mmol) and t-butoxysodium (2.7 mg, 0.028 mmol) were added. , Stirred at 140 ° C. for 30 minutes under microwave irradiation. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, the organic layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 29 (4.0 mg, 67%).
[M + H] = 593.15, measurement condition C
Step 9
Compound 29 (4.0 mg, 0.007 mmol) was dissolved in tetrahydrofuran (0.5 mL), a 2N aqueous hydrochloric acid solution (0.10 mL, 0.202 mmol) was added, and the mixture was stirred for 3 hours. The solvent was distilled off under reduced pressure, and the obtained residue was dissolved in toluene (0.5 mL). Then, 2-methylsulfonylacetic acid (4.8 mg, 0.035 mmol) and dicyclohexylcarbodiimide (7.2 mg, 0.035 mmol) were added, and the mixture was stirred for 30 minutes. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, the organic layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by reverse phase column chromatography to obtain Compound I-201 (1.0 mg, 2-step yield 26%).
¹ H-NMR (CDCl ₃ ) δ: 2.26-2.27 (m, 1H), 2.44-2.51 (m, 1H), 2.93-3.07 (m, 2H), 3.15 (s, 2H), 3.18-3.32 (m, 2H), 3.93-4.18 (m, 2H), 4.30-4.37 (m, 2H), 5.59-5.87 (m, 1H), 6.83-6.89 (m, 2H), 7.19-7.20 (m, 1H), 7.30- 7.32 (m, 1H), 7.38-7.43 (m, 3H), 7.76 (d, J = 7.8 Hz, 1H), 8.19-8.79 (m, 1H).

工程１
既知化合物３０（１８．３ｇ、８０．０ｍｍｏｌ）のエタノール（９１ｍＬ）溶解に、アンモニア水（１３９ｍＬ）を加えて１００℃で９時間撹拌した。反応液を濃縮し、水を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をテトラヒドロフラン（５８ｍＬ）に溶解させ、２－シアノ酢酸（８．１３ｇ、９６．０ｍｍｏｌ）と1-エチル-3-(3-ジメチルアミノプロピル)カルボジイミド塩酸塩（１８．３ｇ、９６．０ｍｍｏｌ）とトリエチルアミン（２６．５ｍＬ、１９１ｍｍｏｌ）を氷冷下加えた後、室温で２時間撹拌した。反応液に塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。有機層を水および飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥し、溶媒を減圧留去した。得られた残渣をシリカゲルクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物３１（１１．３ｇ、収率７６％）をエチルエステル体との混合物として得た。
¹H-NMR (CDCl₃) δ: 1.44(s, 10H), 3.06(d, J = 7.9 Hz, 2H), 3.36(s, 2H), 3.72(s, 3H), 3.93(d, J=9.8 Hz, 2H), 4.06(d, J=9.7 Hz, 2H).
工程２
化合物３１（１１．３ｇ、３６．４ｍｍｏｌ）をメタノール（６０ｍＬ）に溶解し、ソジウムメトキシドの２８％メタノール溶液（１４．６ｍＬ、７２．８ｍｍｏｌ）を加え、室温下１時間撹拌した。反応液を１ｍｏｌ／Ｌ塩酸水溶液（３６．４ｍＬ）に注ぎ、水を加え、酢酸エチルで抽出した。有機層を水で洗浄した後、無水硫酸マグネシウムで乾燥し、溶媒を減圧留去した。得られた残渣をジクロロエタン（１４２ｍＬ）に溶解し、ＤＭＦ（０．２７．８ｍＬ、３５７ｍｍｏｌ）を加え、続いて氷冷下で塩化ホスホリル（４．９８ｍＬ、５３．６ｍｍｏｌ）を加え、室温に昇温して２時間撹拌した。反応液に飽和重層水を加え、酢酸エチルで抽出し、有機層を無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物３２（６．６０ｇ、６１％）を得た。
¹H-NMR (CDCl₃) δ: 1.45(s, 9H), 3.22(s, 2H), 3.94-4.00(m, 4H), 6.32(s, 1H).
工程３
化合物３２（２．００ｇ、６．７２ｍｍｏｌ）のエタノール（２０ｍＬ）溶液に、６－ヒドラジニルニコチノニトリル（９９１ｍｇ、７．３９ｍｍｏｌ）と炭酸水素ナトリウム（７３４ｍｇ、８．７３ｍｍｏｌ）を加え、８０℃にて３時間撹拌した。析出した固体を濾取し、エタノールと水で洗浄することで、化合物３３（１．７３ｇ、収率６５％）を得た。
¹H-NMR (CDCl₃) δ: 1.44(s, 9H), 3.12(s, 2H), 3.91(d, J=9.0 Hz, 2H), 4.01(d, J=9.0 Hz, 2H), 5.63(s, 1H), 7.19(br-s, 2H), 8.01-8.07(m, 2H), 8.66(s, 1H).
工程４
化合物３３（１０３ｍｇ、０．２６ｍｍｏｌ）のジクロロメタン（２ｍＬ）溶液に、トリフルオロ酢酸（１．０ｍＬ、１３．０ｍｍｏｌ）を加え、室温にて１時間撹拌した。濃縮後、メタノールを加え、析出した固体を濾取することで、化合物３４（８２ｍｇ、収率７７％）を得た。
¹H-NMR (DMSO-D₆) δ: 3.24(s, 2H), 3.90(d, J=11.4 Hz, 2H), 4.07(d, J=11.4 Hz, 2H), 7.58(s, 2H), 7.95(d, J=8.9 Hz, 1H), 8.07(s, 1H), 8.42(dd, J=8.8, 2.3 Hz, 1H), 8.92-9.01(m, 2H).
工程５
フェノール（２０．２ｍｇ、０．２２ｍｍｏｌ）をジオキサン（１ｍＬ）に溶解し、カリウムターシャリーブトキシド（２３．０ｍｇ、０．２１ｍｍｏｌ）を加え、室温にて１０分間撹拌した。反応液に、化合物３４（４０ｍｇ、０．０９８ｍｍｏｌ）、５－[ジ(１－アダマンチル)ホスフィノ]－１’,３’,５’－トリフェニル－１’Ｈ－[１,４’]ビピラゾール（１３．０ｍｇ、０．０２０ｍｍｏｌ）、アリルパラジウムクロライドダイマー（１．８ｍｇ、０．００５ｍｍｏｌ）と１－ブロモ－４－（トリフルオロメチル）ベンゼン（２６．４ｍｇ、０．１２ｍｍｏｌ）を加え、９０℃にて２時間撹拌した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物３５（３０．４ｍｇ、４７％）を得た。
¹H-NMR (DMSO-D₆) δ: 3.17(s, 2H), 3.86(d, J=7.8 Hz, 2H), 4.00(d, J=7.8 Hz, 2H), 6.57(d, J=8.5 Hz, 2H), 7.47-7.54(m, 4H), 7.95(d, J=8.8 Hz, 1H), 8.00(s, 1H), 8.40-8.42(m, 1H), 8.93(s, 1H).
工程６
化合物３５（３０．４ｍｇ、０．０５３ｍｍｏｌ）のジクロロメタン（０．６ｍＬ）溶液に、２－（メタンスルホニル）アセチルクロライド（０．２８ｍｍｏｌ）とピリジン（０．０２２ｍｌ、０．２８ｍｍｏｌ）を０℃で加え、１時間撹拌した。室温下、水を加え、酢酸エチルで抽出し、硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール）により精製して化合物ＩＩ－１４（１８．２ｍｇ、４７％）を得た。
¹H-NMR (DMSO-D₆) δ: 3.13(s, 3H), 3.31(s, 2H), 3.90(d, J=7.8 Hz, 2H), 4.05(d, J=7.8 Hz, 2H), 4.37(s, 2H), 6.58(d, J=8.5 Hz, 2H), 7.49(d, J=8.8 Hz, 2H), 7.96(d, J=8.5 Hz, 1H), 8.49(dd, J=8.8, 2.3 Hz, 1H), 8.55(s, 1H), 8.88(d, J=1.8 Hz, 1H), 11.16(s, 1H). Example 9

Process 1
Ammonia water (139 mL) was added to the solution of known compound 30 (18.3 g, 80.0 mmol) in ethanol (91 mL), and the mixture was stirred at 100 ° C. for 9 hours. The reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (58 mL), 2-cyanoacetic acid (8.13 g, 96.0 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride. After adding (18.3 g, 96.0 mmol) and triethylamine (26.5 mL, 191 mmol) under ice-cooling, the mixture was stirred at room temperature for 2 hours. An aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel chromatography (hexane-ethyl acetate) to obtain Compound 31 (11.3 g, yield 76%) as a mixture with an ethyl ester compound.
¹ H-NMR (CDCl ₃ ) δ: 1.44 (s, 10H), 3.06 (d, J = 7.9 Hz, 2H), 3.36 (s, 2H), 3.72 (s, 3H), 3.93 (d, J = 9.8) Hz, 2H), 4.06 (d, J = 9.7 Hz, 2H).
Step 2
Compound 31 (11.3 g, 36.4 mmol) was dissolved in methanol (60 mL), a 28% methanol solution of sodium methoxydo (14.6 mL, 72.8 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into a 1 mol / L hydrochloric acid aqueous solution (36.4 mL), water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was dissolved in dichloroethane (142 mL), DMF (0.27.8 mL, 357 mmol) was added, and then phosphoryl chloride (4.98 mL, 53.6 mmol) was added under ice-cooling, and the temperature was raised to room temperature. And stirred for 2 hours. Saturated layered water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 32 (6.60 g, 61%).
¹ H-NMR (CDCl ₃ ) δ: 1.45 (s, 9H), 3.22 (s, 2H), 3.94-4.00 (m, 4H), 6.32 (s, 1H).
Process 3
To a solution of compound 32 (2.00 g, 6.72 mmol) in ethanol (20 mL), 6-hydrazinylnicotinhonitrile (991 mg, 7.39 mmol) and sodium hydrogen carbonate (734 mg, 8.73 mmol) were added, and the temperature was 80 ° C. Was stirred for 3 hours. The precipitated solid was collected by filtration and washed with ethanol and water to give compound 33 (1.73 g, yield 65%).
¹ H-NMR (CDCl ₃ ) δ: 1.44 (s, 9H), 3.12 (s, 2H), 3.91 (d, J = 9.0 Hz, 2H), 4.01 (d, J = 9.0 Hz, 2H), 5.63 ( s, 1H), 7.19 (br-s, 2H), 8.01-8.07 (m, 2H), 8.66 (s, 1H).
Step 4
Trifluoroacetic acid (1.0 mL, 13.0 mmol) was added to a solution of compound 33 (103 mg, 0.26 mmol) in dichloromethane (2 mL), and the mixture was stirred at room temperature for 1 hour. After concentration, methanol was added, and the precipitated solid was collected by filtration to give compound 34 (82 mg, yield 77%).
¹ H-NMR (DMSO-D ₆ ) δ: 3.24 (s, 2H), 3.90 (d, J = 11.4 Hz, 2H), 4.07 (d, J = 11.4 Hz, 2H), 7.58 (s, 2H), 7.95 (d, J = 8.9 Hz, 1H), 8.07 (s, 1H), 8.42 (dd, J = 8.8, 2.3 Hz, 1H), 8.92-9.01 (m, 2H).
Step 5
Phenol (20.2 mg, 0.22 mmol) was dissolved in dioxane (1 mL), potassium tertiary butoxide (23.0 mg, 0.21 mmol) was added, and the mixture was stirred at room temperature for 10 minutes. In the reaction solution, compound 34 (40 mg, 0.098 mmol), 5- [di (1-adamantyl) phosphino] -1', 3', 5'-triphenyl-1'H- [1,4'] bipyrazole ( Add 13.0 mg, 0.020 mmol), allylpalladium chloride dimer (1.8 mg, 0.005 mmol) and 1-bromo-4- (trifluoromethyl) benzene (26.4 mg, 0.12 mmol) to 90 ° C. And stirred for 2 hours. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 35 (30.4 mg, 47%).
¹ H-NMR (DMSO-D ₆ ) δ: 3.17 (s, 2H), 3.86 (d, J = 7.8 Hz, 2H), 4.00 (d, J = 7.8 Hz, 2H), 6.57 (d, J = 8.5) Hz, 2H), 7.47-7.54 (m, 4H), 7.95 (d, J = 8.8 Hz, 1H), 8.00 (s, 1H), 8.40-8.42 (m, 1H), 8.93 (s, 1H).
Step 6
To a solution of compound 35 (30.4 mg, 0.053 mmol) in dichloromethane (0.6 mL) was added 2- (methanesulfonyl) acetyl chloride (0.28 mmol) and pyridine (0.022 ml, 0.28 mmol) at 0 ° C. The mixture was stirred for 1 hour. At room temperature, water was added, the mixture was extracted with ethyl acetate, and dried over sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain Compound II-14 (18.2 mg, 47%).
¹ H-NMR (DMSO-D ₆ ) δ: 3.13 (s, 3H), 3.31 (s, 2H), 3.90 (d, J = 7.8 Hz, 2H), 4.05 (d, J = 7.8 Hz, 2H), 4.37 (s, 2H), 6.58 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 7.96 (d, J = 8.5 Hz, 1H), 8.49 (dd, J = 8.8) , 2.3 Hz, 1H), 8.55 (s, 1H), 8.88 (d, J = 1.8 Hz, 1H), 11.16 (s, 1H).

工程１
化合物３６（４．５ｇ（純度７８％）、１１．１１ｍｍｏｌ）のメタノール（３０ｍＬ）溶液に、氷冷下水素化ホウ素ナトリウム（４０８ｍｇ、１０．８０ｍｍｏｌ）を加え、０℃にて１時間撹拌した。氷冷下反応液に飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出した。有機層を水および飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物３７（４．６６ｇ（純度７８％）、収率１０３％）を得た。
工程２
アリルアルコール（４．８４ｍＬ、７１．２ｍｍｏｌ）のジメチルスルホキシド（４０ｍＬ）溶液に、カリウムターシャリーブトキシド（８．７９ｇ、７８ｍｍｏｌ）をゆっくりと加え、室温にて３０分撹拌した。反応液に化合物３７（４．５ｇ（純度７８％）、１１．１１ｍｍｏｌ）のジメチルスルホキシド（５ｍＬ）溶液を加え、更に室温下１時間撹拌した。氷冷下反応液に２ｍｏｌ／Ｌ塩酸水溶液を加え撹拌した後、酢酸エチルで抽出した。有機層を水および飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物３８（１．６５ｇ、収率４９％）を得た。
¹H-NMR (CDCl₃) δ: 2.01-2.08(m, 2H), 2.31(ddt, J=23.8, 13.1, 4.0 Hz, 2H), 2.75(s, 1H), 3.44(t, J=9.4 Hz, 1H), 3.57(dd, J=9.7, 3.2 Hz, 1H), 4.01(t, J=6.0 Hz, 2H), 4.07(dd, J=4.5, 1.2 Hz, 2H), 4.86(dd, J=9.0, 3.0 Hz, 1H), 5.21(dd, J=10.6, 1.6 Hz, 1H), 5.29(dd, J=17.3, 1.6 Hz, 1H), 5.93(ddd, J=22.6, 10.6, 5.5 Hz, 1H), 6.87(d, J=8.5 Hz, 2H), 7.31(d, J=8.5 Hz, 2H).
工程３
化合物３８（１．６５ｇ、５．４２ｍｍｏｌ）のジクロロメタン（１５ｍＬ）溶液に、氷冷下デス－マーチン試薬（２．５３ｇ、５．９６ｍｍｏｌ）を加え、室温にて１．５時間撹拌した。反応液に、飽和重曹水を加え、酢酸エチルにて抽出した。有機層を１０％チオ硫酸ナトリウム水溶液及び飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物３９（７６０ｍｇ、４６％）を得た。
¹H-NMR (CDCl₃) δ: 2.04-2.13(m, 2H), 2.26-2.40(m, 2H), 4.09(t, J=6.0 Hz, 2H), 4.13-4.16(m, 2H), 4.70(s, 2H), 5.24(dd, J=10.4, 1.5 Hz, 1H), 5.33(dq, J=17.3, 1.5 Hz, 1H), 5.91-6.01(m, 1H), 6.93(dt, J=9.5, 2.3 Hz, 2H), 7.94(dt, J=9.5, 2.3 Hz, 2H).
工程４
化合物３９（７６０ｍｇ、２．５１ｍｍｏｌ）のエタノール（１０ｍＬ）溶液に、ヒドロキシルアミン塩酸塩（３４９ｍｇ、５．０３ｍｍｏｌ）と酢酸ナトリウム（４１２ｍｇ、５．０３ｍｍｏｌ）を加え、４時間加熱還流下撹拌した。不溶物をろ去後、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）により精製して化合物４０（５６７ｍｇ、７１％）を得た。
¹H-NMR (CDCl₃) δ: 2.02-2.11(m, 3H), 2.25-2.39(m, 2H), 4.00(dt, J=5.7, 1.3 Hz, 2H), 4.04(t, J=6.0 Hz, 2H), 4.70(s, 2H), 5.19(dd, J=10.4, 1.4 Hz, 1H), 5.27(dq, J=17.2, 1.5 Hz, 1H), 5.84-5.93(m, 1H), 6.88(dt, J=9.5, 2.4 Hz, 2H), 7.63-7.68(m, 3H).
工程５
化合物４０（７２９ｍｇ、２．３０ｍｍｏｌ）をトルエン（５ｍｌ）に溶解し、ヒドロキノン（７５９ｍｇ、６．８９ｍｍｏｌ）を加え２４時間加熱還流下撹拌した。不溶物をろ去後、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）により精製して化合物４１（６８０ｍｇ、９３％）を得た。
¹H-NMR (CDCl₃) δ: 2.01-2.08(m, 2H), 2.24-2.38(m, 2H), 3.28-3.33(m, 1H), 3.78-4.54(m, 8H), 5.16(s, 1H), 6.88(dt, J=9.5, 2.5 Hz, 2H), 7.42(s, 2H).
工程６
化合物４１（６７５ｍｇ、２．１３ｍｍｏｌ）のエタノール（７ｍｌ）溶液に、２．５％ロジウム－カーボン（４３８ｍｇ、０．１０６ｍｍｏｌ）を加え、水素雰囲気下室温にて６時間撹拌した。セライト濾過後、反応液を濃縮し、化合物４２（６４２ｍｇ、９５％）を得た。
¹H-NMR (CDCl₃) δ: 2.02-2.09(m, 2H), 2.26-2.38(m, 2H), 2.45-2.55(m, 1H), 3.68-3.76(m, 2H), 3.84-3.91(m, 1H), 3.99-4.07(m, 3H), 4.10-4.16(m, 2H), 6.90(d, J=7.8 Hz, 2H), 7.43(d, J=7.8 Hz, 2H).
工程７
化合物４２（２９６ｍｇ、０．９３ｍｍｏｌ）のテトラヒドロフラン（３ｍｌ）溶液に、二炭酸ジ－ｔｅｒｔ－ブチル（６０７ｍｇ、２．７８ｍｍｏｌ）を加え、室温下２４時間撹拌した。溶媒を減圧留去後、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン‐酢酸エチル）により精製して化合物４３（２９２ｍｇ、７５％）を得た。
¹H-NMR (CDCl₃) δ: 1.40(s, 9H), 1.99-2.08(m, 2H), 2.24-2.38(m, 2H), 3.19(s, 1H), 3.45(s, 1H), 3.61(t, J=8.5 Hz, 1H), 3.73-3.84(m, 3H), 3.94(d, J=9.5 Hz, 1H), 4.00(t, J=5.9 Hz, 2H), 4.12(t, J=8.6 Hz, 1H), 5.77(s, 1H), 6.85(d, J=8.7 Hz, 2H), 7.45(d, J=8.7 Hz, 2H).
工程８
化合物４３（２９０ｍｇ、０．６９ｍｍｏｌ）のジクロロメタン（３ｍｌ）溶液に、氷冷下デス－マーチン試薬（３２３ｍｇ、０．７６１ｍｍｏｌ）を加え、室温にて１時間撹拌した。反応液に、飽和重曹水を加え、酢酸エチルにて抽出した。有機層を１０％チオ硫酸ナトリウム水溶液及び飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物４４（２４８ｍｇ、８６％）を得た。
¹H-NMR (CDCl₃) δ: 1.32(brs, 9H), 2.01-2.08(m, 3H), 2.24-2.39(m, 2H), 3.64(t, J=6.5 Hz, 1H), 3.96-4.21(m, 4H), 4.41(dd, J=9.2, 7.4 Hz, 1H), 5.50(s, 1H), 6.89(dt, J=9.6, 2.7 Hz, 2H), 7.37(dt, J=9.6, 2.7 Hz, 2H), 9.82(d, J=2.4 Hz, 1H).
工程９
化合物４４（２４５ｍｇ、０．５９ｍｍｏｌ）及び２－メチル２－ブテン（６２２ｍｌ、５．９ｍｍｏｌ）のｔｅｒｔ－ブタノール（３ｍｌ）溶液に、リン酸二水素ナトリウム（３５２ｍｇ、２．９３ｍｍｏｌ）水溶液（０．５ｍｌ）、亜塩素酸ナトリウム（１５９ｍｇ、１．７６ｍｍｏｌ）水溶液（０．５ｍｌ）を順次加え、室温にて２時間撹拌した。反応液に１０％クエン酸水溶液を加え、クロロホルムにて抽出した。無水硫酸ナトリウムで乾燥した後、溶媒を減圧留去し、粗生成物として化合物４５（２５４ｍｇ、９９％）を得た。
工程１０
化合物４５（２５０ｍｇ、０．５８ｍｍｏｌ）のアセトン（４ｍｌ）溶液に、ジメチルホルムアミド（１ｍｌ）、炭酸カリウム（１７６ｍｇ、１．２６ｍｍｏｌ）、ヨウ化メチル（０．０８ｍｌ、１．２６ｍｍｏｌ）を加え、７時間撹拌した。反応液に水を加え、酢酸エチルにて抽出した。有機層を水及び飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物４６（２００ｍｇ、７８％）を得た。
¹H-NMR (CDCl₃) δ: 1.38(s, 9H), 1.99-2.08(m, 2H), 2.24-2.38(m, 2H), 3.32(s, 1H), 3.71(s, 3H), 4.00(t, J=6.0 Hz, 2H), 4.10-4.45(m, 4H), 6.25(s, 1H), 6.85(dt, J=9.6, 2.6 Hz, 2H), 7.32(dt, J=9.6, 2.6 Hz, 2H).
工程１１
化合物４６（１９０ｍｇ、０．４２５ｍｍｏｌ）に４ｍｏｌ／Ｌ塩酸－酢酸エチル溶液（２ｍｌ、８ｍｍｏｌ）を加え、室温で２時間撹拌した。溶媒を減圧留去後、テトラヒドロフラン（２ｍｌ）を加え、ＨＡＴＵ（２０６ｍｇ、０．５４ｍｍｏｌ）、２－シアノ酢酸（４６．１ｍｇ、０．５４ｍｍｏｌ）及びトリエチルアミン（０．１７ｍｌ、１．２５ｍｍｏｌ）を加え、室温下１０時間撹拌した。反応液に１０％クエン酸水溶液を加え、酢酸エチルで抽出した。有機層を１０％クエン酸水溶液、飽和重曹水、飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物４７（１３５ｍｇ、７８％）を得た。
¹H-NMR (CDCl₃) δ: 2.01-2.08(m, 2H), 2.23-2.37(m, 2H), 3.31-3.44(m, 3H), 3.79(s, 3H), 4.00(t, J=6.0 Hz, 2H), 4.08-4.15(m, 1H), 4.29-4.38(m, 2H), 4.66(d, J=9.7 Hz, 1H), 6.86(dt, J=9.6, 2.6 Hz, 2H), 7.26(dt, J=9.6, 2.6 Hz, 2H), 8.48(s, 1H).
工程１２
化合物４７（１３０ｍｇ、０．３１ｍｍｏｌ）のメタノール（１ｍｌ）溶液に、氷冷下１ｍｏｌ／Ｌナトリウムメトキシド－メタノール溶液（０．９４ｍｌ、０．９４ｍｍｏｌ）を加え、室温にて１時間撹拌した。反応液を水で希釈後、１ｍｏｌ／Ｌ塩酸水溶液でｐＨ＝４程度に調整し、酢酸エチルにて抽出した。有機層を０．１ｍｏｌ／Ｌ塩酸水溶液、飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去後、１，２－ジクロロエタン（２ｍｌ）、オキシ塩化リン（０．０４１ｍｌ、０．５２ｍｍｏｌ）、２，６－ルチジン（０．０２ｍｌ、０．１７ｍｍｏｌ）を加え、室温にて１４時間撹拌した。反応液に０．１ｍｏｌ／Ｌ塩酸水溶液を加え、酢酸エチルで抽出した。有機層を０．１ｍｏｌ／Ｌ塩酸水溶液、飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物４８（１０１ｍｇ、８０％）を得た。
工程１３
化合物４８（９５ｍｇ、０．２４ｍｍｏｌ）の２－プロパノール（２ｍｌ）溶液に、化合物４９（７１．２ｍｇ、０．３６ｍｍｏｌ）、炭酸水素ナトリウム（３０ｍｇ、０．３６ｍｍｏｌ）を加え、８０℃にて１８時間撹拌した。セライト濾過後、溶媒を減圧留去し、残渣に２ｍｏｌ／Ｌ塩酸－メタノール溶液（６ｍｌ、１２ｍｍｏｌ）を加え、５０℃にて２時間撹拌した。溶媒を減圧留去後、飽和重曹水を加え、酢酸エチルにて抽出した。有機層を飽和重曹水、飽和食塩水で洗浄後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物５０（７６．４ｍｇ、６９％）を得た。
¹H-NMR (CDCl₃) δ: -0.04-0.05(m, 2H), 0.40-0.48(m, 2H), 0.57-0.69(m, 1H), 1.67(q, J=7.0 Hz, 2H), 1.98-2.08(m, 2H), 2.23-2.35(m, 2H), 3.66(t, J=8.2 Hz, 1H), 3.89(t, J=6.8 Hz, 2H), 3.99(t, J=6.0 Hz, 2H), 4.07(t, J=8.2 Hz, 2H), 4.29(d, J=9.4 Hz, 1H), 4.40(t, J=8.2 Hz, 1H), 4.79(s, 2H), 5.35(s, 1H), 6.85(d, J=8.8 Hz, 2H), 7.33(d, J=8.8 Hz, 2H).
工程１４
化合物５０（７５ｍｇ、０．１６ｍｍｏｌ）をトルエン（２ｍｌ）に懸濁させ、ジシクロヘキシルカルボジイミド（１００ｍｇ、０．４８ｍｍｏｌ）、２－メチルスルホニル酢酸（６７ｍｇ、０．４８ｍｍｏｌ）を加え、室温下１８時間撹拌した。不溶物をろ過後、溶媒を減圧留去し、残渣をアミノシリカゲルカラムクロマトグラフィー（クロロホルム－メタノール）により精製した。得られた化合物をＳＦＣ（ＩＤカラム（ダイセル製）、ＭｅＯＨ ３０％）にて光学分割した。
化合物ＩＩ－２またはＩＩ－３
¹H-NMR (CDCl₃) δ: -0.07--0.01(m, 2H), 0.35-0.41(m, 2H), 0.54-0.66(m, 1H), 1.74(q, J=7.2 Hz, 2H), 1.98-2.07(m, 2H), 2.21-2.35(m, 2H), 3.22(s, 3H), 3.79(t, J=8.2 Hz, 1H), 3.95(t, J=5.9 Hz, 2H), 4.01-4.09(m, 3H), 4.14(d, J=9.7 Hz, 1H), 4.19-4.37(m, 3H), 4.45(t, J=8.4 Hz, 1H), 6.40(s, 1H), 6.79(d, J=8.8 Hz, 2H), 7.26(d, J=8.8 Hz, 2H), 9.74(s, 1H).
化合物ＩＩ－２またはＩＩ－３
¹H-NMR (CDCl₃) δ: -0.07--0.01(m, 2H), 0.35-0.41(m, 2H), 0.54-0.66(m, 1H), 1.74(q, J=7.2 Hz, 2H), 1.98-2.07(m, 2H), 2.21-2.35(m, 2H), 3.22(s, 3H), 3.79(t, J=8.2 Hz, 1H), 3.95(t, J=5.9 Hz, 2H), 4.01-4.09(m, 3H), 4.14(d, J=9.7 Hz, 1H), 4.19-4.37(m, 3H), 4.45(t, J=8.4 Hz, 1H), 6.40(s, 1H), 6.79(d, J=8.8 Hz, 2H), 7.26(d, J=8.8 Hz, 2H), 9.74(s, 1H). Example 10

Process 1
Sodium borohydride (408 mg, 10.80 mmol) under ice-cooling was added to a solution of compound 36 (4.5 g (purity 78%), 11.11 mmol) in methanol (30 mL), and the mixture was stirred at 0 ° C. for 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction solution under ice-cooling, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 37 (4.66 g (purity 78%), yield 103%).
Step 2
Potassium tertiary buttoxide (8.79 g, 78 mmol) was slowly added to a solution of allyl alcohol (4.84 mL, 71.2 mmol) in dimethyl sulfoxide (40 mL), and the mixture was stirred at room temperature for 30 minutes. A solution of compound 37 (4.5 g (purity 78%), 11.11 mmol) in dimethyl sulfoxide (5 mL) was added to the reaction mixture, and the mixture was further stirred at room temperature for 1 hour. A 2 mol / L hydrochloric acid aqueous solution was added to the reaction solution under ice-cooling, the mixture was stirred, and then the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 38 (1.65 g, yield 49%).
¹ H-NMR (CDCl ₃ ) δ: 2.01-2.08 (m, 2H), 2.31 (ddt, J = 23.8, 13.1, 4.0 Hz, 2H), 2.75 (s, 1H), 3.44 (t, J = 9.4 Hz) , 1H), 3.57 (dd, J = 9.7, 3.2 Hz, 1H), 4.01 (t, J = 6.0 Hz, 2H), 4.07 (dd, J = 4.5, 1.2 Hz, 2H), 4.86 (dd, J = 9.0, 3.0 Hz, 1H), 5.21 (dd, J = 10.6, 1.6 Hz, 1H), 5.29 (dd, J = 17.3, 1.6 Hz, 1H), 5.93 (ddd, J = 22.6, 10.6, 5.5 Hz, 1H) ), 6.87 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.5 Hz, 2H).
Process 3
A Dess-Martin reagent (2.53 g, 5.96 mmol) under ice-cooling was added to a solution of compound 38 (1.65 g, 5.42 mmol) in dichloromethane (15 mL), and the mixture was stirred at room temperature for 1.5 hours. Saturated aqueous sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous sodium thiosulfate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 39 (760 mg, 46%).
¹ H-NMR (CDCl ₃ ) δ: 2.04-2.13 (m, 2H), 2.26-2.40 (m, 2H), 4.09 (t, J = 6.0 Hz, 2H), 4.13-4.16 (m, 2H), 4.70 (s, 2H), 5.24 (dd, J = 10.4, 1.5 Hz, 1H), 5.33 (dq, J = 17.3, 1.5 Hz, 1H), 5.91-6.01 (m, 1H), 6.93 (dt, J = 9.5) , 2.3 Hz, 2H), 7.94 (dt, J = 9.5, 2.3 Hz, 2H).
Step 4
Hydroxylamine hydrochloride (349 mg, 5.03 mmol) and sodium acetate (412 mg, 5.03 mmol) were added to a solution of compound 39 (760 mg, 2.51 mmol) in ethanol (10 mL), and the mixture was stirred under heating under reflux for 4 hours. After removing the insoluble material by filtration, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 40 (567 mg, 71%).
¹ H-NMR (CDCl ₃ ) δ: 2.02-2.11 (m, 3H), 2.25-2.39 (m, 2H), 4.00 (dt, J = 5.7, 1.3 Hz, 2H), 4.04 (t, J = 6.0 Hz) , 2H), 4.70 (s, 2H), 5.19 (dd, J = 10.4, 1.4 Hz, 1H), 5.27 (dq, J = 17.2, 1.5 Hz, 1H), 5.84-5.93 (m, 1H), 6.88 ( dt, J = 9.5, 2.4 Hz, 2H), 7.63-7.68 (m, 3H).
Step 5
Compound 40 (729 mg, 2.30 mmol) was dissolved in toluene (5 ml), hydroquinone (759 mg, 6.89 mmol) was added, and the mixture was stirred under heating under reflux for 24 hours. After removing the insoluble material by filtration, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 41 (680 mg, 93%).
¹ H-NMR (CDCl ₃ ) δ: 2.01-2.08 (m, 2H), 2.24-2.38 (m, 2H), 3.28-3.33 (m, 1H), 3.78-4.54 (m, 8H), 5.16 (s, 1H), 6.88 (dt, J = 9.5, 2.5 Hz, 2H), 7.42 (s, 2H).
Step 6
2.5% rhodium-carbon (438 mg, 0.106 mmol) was added to a solution of compound 41 (675 mg, 2.13 mmol) in ethanol (7 ml), and the mixture was stirred at room temperature for 6 hours under a hydrogen atmosphere. After filtration through cerite, the reaction solution was concentrated to give compound 42 (642 mg, 95%).
¹ H-NMR (CDCl ₃ ) δ: 2.02-2.09 (m, 2H), 2.26-2.38 (m, 2H), 2.45-2.55 (m, 1H), 3.68-3.76 (m, 2H), 3.84-3.91 ( m, 1H), 3.99-4.07 (m, 3H), 4.10-4.16 (m, 2H), 6.90 (d, J = 7.8 Hz, 2H), 7.43 (d, J = 7.8 Hz, 2H).
Step 7
Di-tert-butyl dicarbonate (607 mg, 2.78 mmol) was added to a solution of compound 42 (296 mg, 0.93 mmol) in tetrahydrofuran (3 ml), and the mixture was stirred at room temperature for 24 hours. After distilling off the solvent under reduced pressure, the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 43 (292 mg, 75%).
¹ H-NMR (CDCl ₃ ) δ: 1.40 (s, 9H), 1.99-2.08 (m, 2H), 2.24-2.38 (m, 2H), 3.19 (s, 1H), 3.45 (s, 1H), 3.61 (t, J = 8.5 Hz, 1H), 3.73-3.84 (m, 3H), 3.94 (d, J = 9.5 Hz, 1H), 4.00 (t, J = 5.9 Hz, 2H), 4.12 (t, J = 8.6 Hz, 1H), 5.77 (s, 1H), 6.85 (d, J = 8.7 Hz, 2H), 7.45 (d, J = 8.7 Hz, 2H).
Step 8
A Dess-Martin reagent (323 mg, 0.761 mmol) under ice-cooling was added to a solution of compound 43 (290 mg, 0.69 mmol) in dichloromethane (3 ml), and the mixture was stirred at room temperature for 1 hour. Saturated aqueous sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous sodium thiosulfate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 44 (248 mg, 86%).
¹ H-NMR (CDCl ₃ ) δ: 1.32 (brs, 9H), 2.01-2.08 (m, 3H), 2.24-2.39 (m, 2H), 3.64 (t, J = 6.5 Hz, 1H), 3.96-4.21 (m, 4H), 4.41 (dd, J = 9.2, 7.4 Hz, 1H), 5.50 (s, 1H), 6.89 (dt, J = 9.6, 2.7 Hz, 2H), 7.37 (dt, J = 9.6, 2.7) Hz, 2H), 9.82 (d, J = 2.4 Hz, 1H).
Step 9
Aqueous solution of sodium dihydrogen phosphate (352 mg, 2.93 mmol) (0.5 ml) in a solution of compound 44 (245 mg, 0.59 mmol) and 2-methyl2-butene (622 ml, 5.9 mmol) in tert-butanol (3 ml). ) And an aqueous solution of sodium chlorite (159 mg, 1.76 mmol) (0.5 ml) were sequentially added, and the mixture was stirred at room temperature for 2 hours. A 10% aqueous citric acid solution was added to the reaction solution, and the mixture was extracted with chloroform. After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain compound 45 (254 mg, 99%) as a crude product.
Step 10
Dimethylformamide (1 ml), potassium carbonate (176 mg, 1.26 mmol) and methyl iodide (0.08 ml, 1.26 mmol) were added to a solution of compound 45 (250 mg, 0.58 mmol) in acetone (4 ml) for 7 hours. Stirred. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 46 (200 mg, 78%).
¹ H-NMR (CDCl ₃ ) δ: 1.38 (s, 9H), 1.99-2.08 (m, 2H), 2.24-2.38 (m, 2H), 3.32 (s, 1H), 3.71 (s, 3H), 4.00 (t, J = 6.0 Hz, 2H), 4.10-4.45 (m, 4H), 6.25 (s, 1H), 6.85 (dt, J = 9.6, 2.6 Hz, 2H), 7.32 (dt, J = 9.6, 2.6) Hz, 2H).
Step 11
A 4 mol / L hydrochloric acid-ethyl acetate solution (2 ml, 8 mmol) was added to compound 46 (190 mg, 0.425 mmol), and the mixture was stirred at room temperature for 2 hours. After distilling off the solvent under reduced pressure, tetrahydrofuran (2 ml) was added, HATU (206 mg, 0.54 mmol), 2-cyanoacetic acid (46.1 mg, 0.54 mmol) and triethylamine (0.17 ml, 1.25 mmol) were added. The mixture was stirred at room temperature for 10 hours. A 10% aqueous citric acid solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous citric acid solution, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 47 (135 mg, 78%).
¹ H-NMR (CDCl ₃ ) δ: 2.01-2.08 (m, 2H), 2.23-2.37 (m, 2H), 3.31-3.44 (m, 3H), 3.79 (s, 3H), 4.00 (t, J = 6.0 Hz, 2H), 4.08-4.15 (m, 1H), 4.29-4.38 (m, 2H), 4.66 (d, J = 9.7 Hz, 1H), 6.86 (dt, J = 9.6, 2.6 Hz, 2H), 7.26 (dt, J = 9.6, 2.6 Hz, 2H), 8.48 (s, 1H).
Step 12
A 1 mol / L sodium methoxide-methanol solution (0.94 ml, 0.94 mmol) was added to a solution of compound 47 (130 mg, 0.31 mmol) in methanol (1 ml) under ice-cooling, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water, adjusted to pH = about 4 with a 1 mol / L hydrochloric acid aqueous solution, and extracted with ethyl acetate. The organic layer was washed with 0.1 mol / L hydrochloric acid aqueous solution and saturated brine, and dried over anhydrous sodium sulfate. After distilling off the solvent under reduced pressure, 1,2-dichloroethane (2 ml), phosphorus oxychloride (0.041 ml, 0.52 mmol) and 2,6-lutidine (0.02 ml, 0.17 mmol) were added, and 14 at room temperature. Stir for hours. A 0.1 mol / L hydrochloric acid aqueous solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with 0.1 mol / L hydrochloric acid aqueous solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 48 (101 mg, 80%).
Step 13
Compound 49 (71.2 mg, 0.36 mmol) and sodium hydrogen carbonate (30 mg, 0.36 mmol) were added to a solution of compound 48 (95 mg, 0.24 mmol) in 2-propanol (2 ml), and the mixture was added at 80 ° C. for 18 hours. Stirred. After filtration through cerite, the solvent was distilled off under reduced pressure, a 2 mol / L hydrochloric acid-methanol solution (6 ml, 12 mmol) was added to the residue, and the mixture was stirred at 50 ° C. for 2 hours. After distilling off the solvent under reduced pressure, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 50 (76.4 mg, 69%).
¹ H-NMR (CDCl ₃ ) δ: -0.04-0.05 (m, 2H), 0.40-0.48 (m, 2H), 0.57-0.69 (m, 1H), 1.67 (q, J = 7.0 Hz, 2H), 1.98-2.08 (m, 2H), 2.23-2.35 (m, 2H), 3.66 (t, J = 8.2 Hz, 1H), 3.89 (t, J = 6.8 Hz, 2H), 3.99 (t, J = 6.0 Hz) , 2H), 4.07 (t, J = 8.2 Hz, 2H), 4.29 (d, J = 9.4 Hz, 1H), 4.40 (t, J = 8.2 Hz, 1H), 4.79 (s, 2H), 5.35 (s) , 1H), 6.85 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 8.8 Hz, 2H).
Step 14
Compound 50 (75 mg, 0.16 mmol) was suspended in toluene (2 ml), dicyclohexylcarbodiimide (100 mg, 0.48 mmol) and 2-methylsulfonylacetic acid (67 mg, 0.48 mmol) were added, and the mixture was stirred at room temperature for 18 hours. .. After filtering the insoluble material, the solvent was distilled off under reduced pressure, and the residue was purified by amino silica gel column chromatography (chloroform-methanol). The obtained compound was optically resolved by SFC (ID column (manufactured by Daicel), MeOH 30%).
Compound II-2 or II-3
¹ H-NMR (CDCl ₃ ) δ: -0.07--0.01 (m, 2H), 0.35-0.41 (m, 2H), 0.54-0.66 (m, 1H), 1.74 (q, J = 7.2 Hz, 2H) , 1.98-2.07 (m, 2H), 2.21-2.35 (m, 2H), 3.22 (s, 3H), 3.79 (t, J = 8.2 Hz, 1H), 3.95 (t, J = 5.9 Hz, 2H), 4.01-4.09 (m, 3H), 4.14 (d, J = 9.7 Hz, 1H), 4.19-4.37 (m, 3H), 4.45 (t, J = 8.4 Hz, 1H), 6.40 (s, 1H), 6.79 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 9.74 (s, 1H).
Compound II-2 or II-3
¹ H-NMR (CDCl ₃ ) δ: -0.07--0.01 (m, 2H), 0.35-0.41 (m, 2H), 0.54-0.66 (m, 1H), 1.74 (q, J = 7.2 Hz, 2H) , 1.98-2.07 (m, 2H), 2.21-2.35 (m, 2H), 3.22 (s, 3H), 3.79 (t, J = 8.2 Hz, 1H), 3.95 (t, J = 5.9 Hz, 2H), 4.01-4.09 (m, 3H), 4.14 (d, J = 9.7 Hz, 1H), 4.19-4.37 (m, 3H), 4.45 (t, J = 8.4 Hz, 1H), 6.40 (s, 1H), 6.79 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 9.74 (s, 1H).

工程１
（Ｒ）－２－メチルプロパン－２－スルフィンアミド（１３４ｇ、１.１１ｍｏｌ）のトルエン（５００ｍＬ）溶液に、テトラエトキシチタン（１４１ｍＬ、６６６ｍｍｏｌ）、化合物５１（１００ｇ、４４４ｍｍｏｌ）のテトラヒドロフラン（２５０ｍＬ）とトルエン（２５０ｍＬ）溶液を加え、９０℃で１２時間撹拌した。反応液に室温下、飽和塩化アンモニウム水溶液を加えた後、酢酸エチルで抽出した。有機層を飽和塩化アンモニウム水溶液で洗浄した後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物５２（８２ｇ、収率５６％）を得た。
¹H-NMR (CDCl₃) δ: 1.32(s, 9H), 3.24-3.31(m, 1H), 3.45-3.53(m, 1H), 4.27-4.41(m, 2H), 7.09-7.12(m, 2H), 7.83(d, 1H, J=8.31 Hz).
工程２
１ｍｏｌ／Ｌリチウムヘキサメチルジシラジド テトラヒドロフラン溶液（３３４ｍＬ、３３３ｍｍｏｌ）に、酢酸メチル（２６．５ｍＬ、３３３ｍｍｏｌ）を－７８℃で加え、１時間撹拌した。反応液に、塩化チタントリイソプロポキド（１１０ｇ、４２４ｍｍｏｌ）のテトラヒドロフラン（２５０ｍＬ）溶液を、－７８℃で滴下し、２時間撹拌した。反応液に、化合物５２（５０．０ｇ、１５１ｍｍｏｌ）のテトラヒドロフラン（２５０ｍＬ）溶液を、－７８℃で滴下し、３０分撹拌した。飽和塩化アンモニウム水溶液とロッシェル塩を加え、室温に昇温して１２時間撹拌した。その後、酢酸エチルで抽出し、有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物５３（３５ｇ、収率５７％）を得た。
¹H NMR (400 MHz, DMSO-d₆) δ: 1.09(s, 9H), 2.26-2.36(m, 2H), 3.04(q, 2H, J=5.6 Hz), 3.53(s, 3H), 4.22-4.26(m, 1H), 4.34-4.37(m, 1H), 5.45(s, 1H), 7.01-7.07(m, 2H), 7.28(d, 1H, J=8.56 Hz).
工程３
化合物５３（１．４ｇ、３．４６ｍｍｏｌ）のジオキサン（１５ｍＬ）溶液に、ビス（ピナコラト）ジボロン（１．３２ｇ、５．１９ｍｍｏｌ）、［１，１’－ビス（ジフェニルホスフィノ）フェロセン］パラジウム（ＩＩ）ジクロリド ジクロロメタン錯体（１：１）（０．１４１ｇ、０．１７ｍｍｏｌ）と酢酸カリウム（１．０２ｇ、１０．４ｍｍｏｌ）を加え、１００℃で４時間撹拌した。反応液に、３０％過酸化水素水（１．９６ｍＬ、１７．３ｍｍｏｌ）を室温下加え、２時間撹拌した。反応液に水を加え、酢酸エチルで抽出し、有機層を１０％チオ硫酸ナトリウム水溶液水で洗浄した後、無水硫ナトリウムで乾燥し、溶媒を減圧留去した。得られた残渣をＤＭＦ（１０ｍＬ）に溶解させ、炭酸セシウム（１．６９ｇ、５．１９ｍｍｏｌ）とトリフルオロメタンスルホン酸２,２,２－トリフルオロエチルエステル（５９７ｍＬ、４．１６ｍｍｍｏｌ）を加え、室温下１２時間撹拌した。反応液に、１０％クエン酸水溶液を加え、酢酸エチルで抽出し、飽和重層水と飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸ナトリウムで乾燥し、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物５４（１．２３ｇ、収率８４％）を得た。
¹H-NMR (CDCl₃) δ: 1.22(s, 9H), 2.21-2.28(m, 1H), 2.52-2.57(m, 1H), 2.77(d, J=15.7 Hz, 1H), 2.96(d, J=15.7 Hz, 1H), 3.71(s, 3H), 4.19-4.25(m, 1H), 4.31(q, J=8.1 Hz, 2H), 4.45-4.51(m, 1H), 5.13(s, 1H), 6.40(d, J=2.6 Hz, 1H), 6.56(dd, J=8.8, 2.6 Hz, 1H), 7.17(d, J=8.8 Hz, 1H).
工程４
化合物５４（５４５ｍｇ、１．２９ｍｍｏｌ）のメタノール（１．１ｍＬ）溶液に、４ｍｏｌ／Ｌ 塩酸ジオキサン溶液（０．６４ｍＬ、２．５７ｍｍｏｌ）を加え、室温で１時間撹拌した。反応液の溶媒を減圧留去した後、得られた残渣をテトラヒドロフラン（４．５ｍｌ）に溶解させ、２－シアノ酢酸（２１９ｍｇ、２．５７ｍｍｏｌ）、1-エチル-3-(3-ジメチルアミノプロピル)カルボジイミド塩酸塩（４９３ｍｇ、２．５７ｍｍｏｌ）とトリエチルアミン（０．７１ｍＬ、５．１５ｍｍｏｌ）を加え、室温で３時間撹拌した。反応液に水を加え、酢酸エチルで抽出し、飽和重層水と飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸ナトリウムで乾燥し、溶媒を減圧留去し、化合物５５（４８３ｍｇ、９７％）を得た。
¹H-NMR (CDCl₃) δ: 2.14-2.20(m, 1H), 2.81-2.88(m, 1H), 3.02(d, J=15.1 Hz, 1H), 3.17(d, J=15.1 Hz, 1H), 3.33(dd, J=20.2, 18.9 Hz, 2H), 3.70(s, 3H), 4.19-4.32(m, 4H), 6.40(d, J=2.8 Hz, 1H), 6.54(dd, J=8.8, 2.8 Hz, 1H), 7.15(s, 1H), 7.20(d, J=8.8 Hz, 1H).
工程５
化合物５５（４９７ｍｇ、１．２９ｍｍｏｌ）のメタノール（２．５ｍＬ）溶液に、２８％ソジウムメトキシド メタノール溶液（９９３ｍｇ、５．１５ｍｍｏｌ）を加え、室温下１時間撹拌した。反応液に２ｍｏｌ／Ｌの塩酸水溶液（６ｍＬ）と水を加え、酢酸エチルで抽出した。有機層を水で洗浄した後、無水硫酸マグネシウムで乾燥した。濃縮後、得られた残渣を酢酸エチルに溶解させ、飽和重層水で逆抽出した。その後、水層に濃塩酸を氷冷下加え、析出した固体を濾取することで、化合物５６（３４０ｍｇ、７５％）を得た。
¹H-NMR (DMSO-D₆) δ: 1.99-2.15(m, 2H), 2.67(d, J=17.3 Hz, 1H), 3.21(d, J=17.3 Hz, 1H), 4.09-4.15(m, 1H), 4.20-4.25(m, 1H), 4.72(q, J=8.9 Hz, 2H), 6.49(d, J=2.6 Hz, 1H), 6.64(dd, J=8.8, 2.6 Hz, 1H), 7.41(d, J=8.8 Hz, 1H), 7.89(s, 1H).
工程６
化合物５６（５００ｍｇ、１．４１ｍｍｏｌ）のジクロロエタン（５ｍＬ）溶液に、塩化ホスホリル（０．１５２ｍＬ、１．６９ｍｍｏｌ）とＤＭＦ（０．１３６ｍＬ、１．７０ｍｍｏｌ）のジクロロエタン（５ｍｌ）溶液を加え、室温で７５時間撹拌した。反応液に水を加え、酢酸エチルで抽出し、飽和重層水と飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸マグネシウムで乾燥し、溶媒を減圧留去し、化合物５７（４８６ｍｇ、９２％）を得た。
¹H-NMR (CDCl₃) δ: 2.24-2.27(m, 2H), 3.00(d, J=18.8 Hz, 1H), 3.43(d, J=18.8 Hz, 1H), 4.17-4.35(m, 4H), 5.92(s, 1H), 6.42(d, J=2.5 Hz, 1H), 6.63(dd, J=8.8, 2.5 Hz, 1H), 7.33(d, J=8.8 Hz, 1H).
工程７
化合物５７（１００ｍｇ、０．２７ｍｍｏｌ）のエタノール（２ｍＬ）溶液に、２－ヒドラジニル－５－メチルピリジン塩酸塩（５１．４ｍｇ、０．３２ｍｍｏｌ）と炭酸水素ナトリウム（５６．３ｍｇ、０．６７ｍｍｏｌ）を加え、７０℃にて７時間撹拌した。その後、水を加え、クロロホルムで抽出し、飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸マグネシウムで乾燥し、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム－メタノール）により精製して化合物５８（７７．６ｍｇ、収率６３％）を得た。
¹H-NMR (CDCl₃) δ: 2.15-2.26(m, 2H), 2.36(s, 3H), 3.01(d, J=16.2 Hz, 1H), 3.27(d, J=16.2 Hz, 1H), 4.21-4.24(m, 2H), 4.32(q, J=8.1 Hz, 2H), 5.20(s, 1H), 6.42(d, J=2.6 Hz, 1H), 6.61(dd, J=8.8, 2.6 Hz, 1H), 7.18(s, 2H), 7.50(d, J=8.8 Hz, 1H), 7.63(dd, J=8.6, 2.2 Hz, 1H), 7.77(d, J=8.4 Hz, 1H), 8.19(s, 1H).
工程８
化合物５８（４３０ｍｇ、０．９４ｍｍｏｌ）のジクロロメタン（５ｍＬ）溶液に、２－（メタンスルホニル）アセチルクロライド（３．７４ｍｍｏｌ）のジクロロメタン（３ｍｌ）溶液とピリジン（０．３０３ｍｌ、３．７４ｍｍｏｌ）を０℃で加え、１時間半撹拌した。室温下、水を加え、酢酸エチルで抽出し、硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール、アミノシリカゲル）により精製して、ヘキサン―酢酸エチルで粉末化させることで化合物Ｉ－２７５（３２０ｍｇ、５９％）を得た。
¹H-NMR (CDCl₃) δ: 2.19-2.31(m, 2H), 2.40(s, 3H), 3.11(d, J=16.3 Hz, 1H), 3.22(s, 3H), 3.41(d, J=16.3 Hz, 1H), 4.14(s, 2H), 4.23-4.25(m, 2H), 4.33(q, J=8.0 Hz, 2H), 5.59(s, 1H), 6.44(d, J=2.6 Hz, 1H), 6.62(dd, J=8.8, 2.6 Hz, 1H), 7.49(d, J=8.8 Hz, 1H), 7.69-7.72(m, 1H), 7.81(d, J=8.3 Hz, 1H), 8.30(br-s, 1H), 11.19(s, 1H). Example 11

Process 1
(R) -2-Methylpropane-2-sulfinamide (134 g, 1.11 mol) in a toluene (500 mL) solution with tetraethoxytitanium (141 mL, 666 mmol) and compound 51 (100 g, 444 mmol) in tetrahydrofuran (250 mL). A solution of toluene (250 mL) was added, and the mixture was stirred at 90 ° C. for 12 hours. A saturated aqueous solution of ammonium chloride was added to the reaction solution at room temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 52 (82 g, yield 56%).
¹ H-NMR (CDCl ₃ ) δ: 1.32 (s, 9H), 3.24-3.31 (m, 1H), 3.45-3.53 (m, 1H), 4.27-4.41 (m, 2H), 7.09-7.12 (m, 2H), 7.83 (d, 1H, J = 8.31 Hz).
Step 2
Methyl acetate (26.5 mL, 333 mmol) was added to a 1 mol / L lithium hexamethyldisilazide tetrahydrofuran solution (334 mL, 333 mmol) at −78 ° C., and the mixture was stirred for 1 hour. A solution of titanium chloride triisopropoxide (110 g, 424 mmol) in tetrahydrofuran (250 mL) was added dropwise to the reaction solution at −78 ° C., and the mixture was stirred for 2 hours. A solution of compound 52 (50.0 g, 151 mmol) in tetrahydrofuran (250 mL) was added dropwise to the reaction solution at −78 ° C., and the mixture was stirred for 30 minutes. A saturated aqueous ammonium chloride solution and a Rochelle salt were added, the temperature was raised to room temperature, and the mixture was stirred for 12 hours. Then, the mixture was extracted with ethyl acetate, the organic layer was washed with water, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 53 (35 g, yield 57%).
¹ H NMR (400 MHz, DMSO-d ₆ ) δ: 1.09 (s, 9H), 2.26-2.36 (m, 2H), 3.04 (q, 2H, J = 5.6 Hz), 3.53 (s, 3H), 4.22 -4.26 (m, 1H), 4.34-4.37 (m, 1H), 5.45 (s, 1H), 7.01-7.07 (m, 2H), 7.28 (d, 1H, J = 8.56 Hz).
Process 3
In a solution of compound 53 (1.4 g, 3.46 mmol) in dichloromethane (15 mL), bis (pinacolato) diboron (1.32 g, 5.19 mmol), [1,1'-bis (diphenylphosphino) ferrocene] palladium ( II) Dichloride dichloromethane complex (1: 1) (0.141 g, 0.17 mmol) and potassium acetate (1.02 g, 10.4 mmol) were added, and the mixture was stirred at 100 ° C. for 4 hours. A 30% hydrogen peroxide solution (1.96 mL, 17.3 mmol) was added to the reaction solution at room temperature, and the mixture was stirred for 2 hours. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, the organic layer was washed with 10% aqueous sodium thiosulfate solution, dried over anhydrous sodium sulfur, and the solvent was evaporated under reduced pressure. The obtained residue is dissolved in DMF (10 mL), cesium carbonate (1.69 g, 5.19 mmol) and trifluoromethanesulfonic acid 2,2,2-trifluoroethyl ester (597 mL, 4.16 m mmol) are added, and room temperature is reached. The mixture was stirred for 12 hours. A 10% aqueous solution of citrate was added to the reaction mixture, the mixture was extracted with ethyl acetate, washed with saturated aqueous layered water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain the obtained residue. Purification by silica gel column chromatography (hexane-ethyl acetate) gave compound 54 (1.23 g, yield 84%).
¹ H-NMR (CDCl ₃ ) δ: 1.22 (s, 9H), 2.21-2.28 (m, 1H), 2.52-2.57 (m, 1H), 2.77 (d, J = 15.7 Hz, 1H), 2.96 (d) , J = 15.7 Hz, 1H), 3.71 (s, 3H), 4.19-4.25 (m, 1H), 4.31 (q, J = 8.1 Hz, 2H), 4.45-4.51 (m, 1H), 5.13 (s, 1H), 6.40 (d, J = 2.6 Hz, 1H), 6.56 (dd, J = 8.8, 2.6 Hz, 1H), 7.17 (d, J = 8.8 Hz, 1H).
Step 4
A 4 mol / L dioxane hydrochloride solution (0.64 mL, 2.57 mmol) was added to a solution of compound 54 (545 mg, 1.29 mmol) in methanol (1.1 mL), and the mixture was stirred at room temperature for 1 hour. After distilling off the solvent of the reaction solution under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (4.5 ml), 2-cyanoacetic acid (219 mg, 2.57 mmol), 1-ethyl-3- (3-dimethylaminopropyl). ) Carbodiimide hydrochloride (493 mg, 2.57 mmol) and triethylamine (0.71 mL, 5.15 mmol) were added, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, washed with saturated aqueous layer water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give compound 55 (483 mg, 97%). rice field.
¹ H-NMR (CDCl ₃ ) δ: 2.14-2.20 (m, 1H), 2.81-2.88 (m, 1H), 3.02 (d, J = 15.1 Hz, 1H), 3.17 (d, J = 15.1 Hz, 1H) ), 3.33 (dd, J = 20.2, 18.9 Hz, 2H), 3.70 (s, 3H), 4.19-4.32 (m, 4H), 6.40 (d, J = 2.8 Hz, 1H), 6.54 (dd, J = 8.8, 2.8 Hz, 1H), 7.15 (s, 1H), 7.20 (d, J = 8.8 Hz, 1H).
Step 5
A 28% sodium methoxydo methanol solution (993 mg, 5.15 mmol) was added to a methanol (2.5 mL) solution of compound 55 (497 mg, 1.29 mmol), and the mixture was stirred at room temperature for 1 hour. A 2 mol / L hydrochloric acid aqueous solution (6 mL) and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over anhydrous magnesium sulfate. After concentration, the obtained residue was dissolved in ethyl acetate and back-extracted with saturated layered water. Then, concentrated hydrochloric acid was added to the aqueous layer under ice-cooling, and the precipitated solid was collected by filtration to obtain compound 56 (340 mg, 75%).
¹ H-NMR (DMSO-D ₆ ) δ: 1.99-2.15 (m, 2H), 2.67 (d, J = 17.3 Hz, 1H), 3.21 (d, J = 17.3 Hz, 1H), 4.09-4.15 (m) , 1H), 4.20-4.25 (m, 1H), 4.72 (q, J = 8.9 Hz, 2H), 6.49 (d, J = 2.6 Hz, 1H), 6.64 (dd, J = 8.8, 2.6 Hz, 1H) , 7.41 (d, J = 8.8 Hz, 1H), 7.89 (s, 1H).
Step 6
To a solution of compound 56 (500 mg, 1.41 mmol) in dichloroethane (5 mL) is added a solution of phosphoryl chloride (0.152 mL, 1.69 mmol) and DMF (0.136 mL, 1.70 mmol) in dichloroethane (5 ml) at room temperature. The mixture was stirred for 75 hours. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, washed with saturated aqueous layer water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to give compound 57 (486 mg, 92%). rice field.
¹ H-NMR (CDCl ₃ ) δ: 2.24-2.27 (m, 2H), 3.00 (d, J = 18.8 Hz, 1H), 3.43 (d, J = 18.8 Hz, 1H), 4.17-4.35 (m, 4H) ), 5.92 (s, 1H), 6.42 (d, J = 2.5 Hz, 1H), 6.63 (dd, J = 8.8, 2.5 Hz, 1H), 7.33 (d, J = 8.8 Hz, 1H).
Step 7
2-Hydradinyl-5-methylpyridine hydrochloride (51.4 mg, 0.32 mmol) and sodium hydrogen carbonate (56.3 mg, 0.67 mmol) in a solution of compound 57 (100 mg, 0.27 mmol) in ethanol (2 mL). In addition, the mixture was stirred at 70 ° C. for 7 hours. Then, water is added, the mixture is extracted with chloroform, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and the obtained residue is purified by silica gel column chromatography (chloroform-methanol). The compound 58 (77.6 mg, yield 63%) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.15-2.26 (m, 2H), 2.36 (s, 3H), 3.01 (d, J = 16.2 Hz, 1H), 3.27 (d, J = 16.2 Hz, 1H), 4.21-4.24 (m, 2H), 4.32 (q, J = 8.1 Hz, 2H), 5.20 (s, 1H), 6.42 (d, J = 2.6 Hz, 1H), 6.61 (dd, J = 8.8, 2.6 Hz) , 1H), 7.18 (s, 2H), 7.50 (d, J = 8.8 Hz, 1H), 7.63 (dd, J = 8.6, 2.2 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 8.19 (s, 1H).
Step 8
A solution of compound 58 (430 mg, 0.94 mmol) in dichloromethane (5 mL), a solution of 2- (methanesulfonyl) acetyl chloride (3.74 mmol) in dichloromethane (3 ml) and pyridine (0.303 ml, 3.74 mmol) at 0 ° C. And stirred for one and a half hours. At room temperature, water was added, the mixture was extracted with ethyl acetate, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform-methanol, amino silica gel) and powdered with hexane-ethyl acetate to give compound I-275 (320 mg, 59%). Obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.19-2.31 (m, 2H), 2.40 (s, 3H), 3.11 (d, J = 16.3 Hz, 1H), 3.22 (s, 3H), 3.41 (d, J) = 16.3 Hz, 1H), 4.14 (s, 2H), 4.23-4.25 (m, 2H), 4.33 (q, J = 8.0 Hz, 2H), 5.59 (s, 1H), 6.44 (d, J = 2.6 Hz) , 1H), 6.62 (dd, J = 8.8, 2.6 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.69-7.72 (m, 1H), 7.81 (d, J = 8.3 Hz, 1H) , 8.30 (br-s, 1H), 11.19 (s, 1H).

工程１
化合物５１（１．７５ｇ、７．６９ｍｍｏｌ）に（Ｓ）－２－メチルプロパン－２－スルフィンアミド（１．０３ｇ、８．４５ｍｍｏｌ）とテトラエトキシチタン（３．２２ｍＬ、６ｍｍｏｌ）を加え、１００℃で２時間半撹拌した。反応液を酢酸エチルと水で希釈し、酢酸エチルで抽出した。有機層を飽和塩化ナトリウム水溶液で洗浄した後、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物５９（１．８６ｇ、収率７３％）を得た。
¹H-NMR (CDCl₃) δ: 1.32(s, 9H), 3.24-3.31(m, 2H), 3.46-3.53(m, 2H), 4.28-4.41(m, 2H), 7.09-7.13(m, 2H), 7.84(d, J=8.4 Hz, 1H).
工程２
１ｍｏｌ／Ｌリチウムヘキサメチルジシラジド テトラヒドロフラン溶液（９．０１ｍＬ、９．０１ｍｍｏｌ）に、テトラヒドロフラン（１５ｍＬ）と酢酸メチル（０．７２ｍＬ、９．０１ｍｍｏｌ）を－７８℃で加え、３０分間撹拌した。反応液に１ｍｏｌ／Ｌ塩化チタントリイソプロポキドのヘキサン溶液（１１．３ｍＬ、１１．３ｍｍｏｌ）－７８℃で滴下し、２０分間撹拌した。その後、化合物５９（１．８６ｇ、５．６３ｍｍｏｌ）のテトラヒドロフラン（１６ｍＬ）溶液を、－７８℃で滴下し、１時間撹拌した。飽和塩化ナトリウム水溶液を加え、酢酸エチルで抽出し、有機層を水で洗浄した後、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物６０（２．０７ｇ、収率７７％）を得た。
¹H-NMR (CDCl₃) δ: 1.22(s, 9H), 2.22-2.29(m, 1H), 2.56-2.61(m, 2H), 2.78(d, J=15.8 Hz, 1H), 2.93(d, J=15.8 Hz, 1H), 3.71(s, 3H), 4.20-4.25(m, 1H), 4.43-4.49(m, 1H), 5.17(s, 1H), 7.02-7.05(m, 2H), 7.11(d, J=8.3 Hz, 1H).
工程３
化合物６０（５１２ｍｇ、１．２２ｍｍｏｌ）の１、４-ジオキサン（５ｍＬ）溶液にビス（ピナコラト）ジボロン（３４１ｍｇ、１．３４ｍｍｏｌ）、酢酸カリウム（３５９ｍｇ、３．６６ｍｍｏｌ）と［１、１’－ビス（ジフェニルホスフィノ）フェロセン］パラジウム（ＩＩ）ジクロリド ジクロロメタン付加物（１９．９ｍｇ、０．０２４ｍｍｏｌ）を加え、減圧、窒素置換を３回繰り返した後３時間加熱還流した。室温に冷却後、不溶物をセライト濾過し溶媒を減圧留去して得られた残渣をテトラヒドロフラン（５ｍＬ）で希釈し、３０％過酸化水素水溶液（２７７ｍｇ、２．４４ｍｍｏｌ）と１ｍｏｌ／Ｌ水酸化ナトリウム水溶液（０．２４４ｍＬ、０．２４４ｍｍｏｌ）を加え室温で１９時間半撹拌した。反応液をチオ硫酸ナトリウム５水和物（６０６ｍｇ、２．４４ｍｍｏｌ）で処理し、酢酸エチルで抽出し、有機層を水で洗浄した後、溶媒を減圧留去し、得られた残渣をヘキサン－酢酸エチルで粉末化し、化合物６１（３９１ｍｇ、収率９４％）を得た。
¹H-NMR (CDCl₃) δ: 1.23(s, 9H), 2.21-2.28(m, 1H), 2.45-2.50(m, 1H), 2.78(d, J=15.9 Hz, 1H), 2.99(d, J=15.9 Hz, 1H), 3.71(s, 3H), 4.17-4.22(m, 1H), 4.43-4.50(m, 1H), 5.10(s, 1H), 6.23(s, 1H), 6.34(s, 1H), 6.40(d, J=8.3 Hz, 1H), 7.05(d, J=8.6 Hz, 1H).
工程４
化合物６１（３８０ｍｇ、１．１１ｍｍｏｌ）のＮ、Ｎ－ジメチルフォルムアミド（１．５ｍＬ）溶液に、２、２、２－トリフルオロエチルトリフルオロメタンスルフォネート（３１０ｍｇ、１．３４ｍｍｏｌ）と炭酸カリウム（１８５ｍｇ、１、３４ｍｍｏｌ）を加え室温で１４時間撹拌後、６０℃に加温しさらに２時間撹拌した。反応液を酢酸エチルと水で希釈し、有機層を水で洗浄した後、溶媒を減圧留去し、得られた残渣のメタノール（２ｍＬ）溶液に４ｍｏｌ／Ｌ塩酸ジオキサン溶液（０．５５７ｍＬ、２．２３ｍｍｏｌ）を加え室温で１時間撹拌した。反応液の溶媒を減圧留去し、さらにトルエンを加えて溶媒を減圧留去し、得られた残渣のジクロロメタン（４ｍＬ）溶液に、２－シアノ酢酸（１６１ｍｇ、１．８９ｍｍｏｌ）、１－（３－ジメチルアミノプロピル）－３－エチルカルボジイミド塩酸塩（３６３ｍｇ、１．８９ｍｍｏｌ）とトリエチルアミン（０．４６３ｍＬ、３．３４ｍｍｏｌ）を加え室温で１９時間撹拌した。反応液の溶媒を減圧留去し、酢酸エチルと水で希釈し、有機層を水で洗浄し、溶媒を減圧留去し、化合物６２の粗生成物を得た。
工程５
化合物６２の粗生成物のメタノール（４ｍＬ）溶液に、６０％水素化ナトリウム（２７０ｍｇ、６．７５ｍｍｏｌ）を加え室温で５時間撹拌した。２ｍｏｌ／Ｌ塩酸水溶液（３．３４ｍＬ、６．６８ｍｍｏｌ）を加えた後に溶媒を減圧留去し、酢酸エチルと水で希釈し、有機層を水で洗浄した後、溶媒を減圧留去し、得られた残渣をヘキサン－酢酸エチルで粉末化し、化合物６３（３２４ｍｇ、収率８２％）を得た。
¹H-NMR (DMSO-D₆) δ: 1.99-2.13(m, 2H), 2.65(d, J=17.1 Hz, 1H), 3.19(d, J=17.1 Hz, 1H), 4.09-4.17(m, 1H), 4.20-4.25(m, 1H), 4.72(q, J=8.9 Hz, 2H), 6.48(d, J=2.3 Hz, 1H), 6.64(dd, J=8.8, 2.3 Hz, 1H), 7.41(d, J=8.8 Hz, 1H), 7.84(s, 1H).
工程６
化合物６３（３０８ｍｇ、０．８６９ｍｍｏｌ）の１、２－ジクロロエタン（６．２ｍＬ）懸濁液に、Ｎ、Ｎ－ジメチルホルムアミド（６３．５ｍｇ、０．８６９ｍｍｏｌ）とオキシ塩化リン（１３３ｍｇ、０．８６９ｍｍｏｌ）加え室温で１８．５時間撹拌した。反応液に水を加え、析出した固体をろ取し化合物６４（３１２ｍｇ、収率９６％）を得た。
¹H-NMR (CDCl₃) δ: 2.26(2H, t, J=5.5 Hz), 3.00(1H, d, J=18.8 Hz), 3.44(1H, d, J=18.8 Hz), 4.15-4.29(2H, m), 4.30(1H, d, J=7.9 Hz), 4.34(1H, d, J=7.9 Hz), 5.83(1H, s), 6.42(1H, d, J=2.5 Hz), 6.63(1H, dd, J=8.8, 2.4 Hz), 7.33(1H, d, J=8.8 Hz).
工程７
化合物６４（５００ｍｇ、１．３４ｍｍｏｌ）のテトラヒドロフラン（４ｍＬ）溶液に、ヒドラジン１水和物（２２５ｍｇ、３．３５ｍｍｏｌ）を加え、室温で１時間撹拌した。反応液に水を加え、酢酸エチルで抽出し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム-メタノール）により精製して化合物６５（４３２ｍｇ、収率８７％）を得た。
［Ｍ＋Ｈ］＝３６９．００、測定条件Ｃ
工程８
化合物６５の（３３３ｍｇ、０．９１ｍｍｏｌ）のアセトニトリル（２ｍＬ）溶液に、化合物６６（３２４ｍｇ、１．０９ｍｍｏｌ）と炭酸セシウム（３９７ｍｇ、１．２２ｍｍｏｌ）を加え、８０℃で１時間半撹拌した。反応液に水を加え、酢酸エチルで抽出し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール）により精製して化合物６７（１３７ｍｇ、収率３１％）を得た。
¹H-NMR (CDCl₃) δ: 2.14-2.26(m, 4H), 2.93(d, J=16.1 Hz, 1H), 3.21(d, J=16.1 Hz, 1H), 3.97-4.03(m, 4H), 4.19-4.21(m, 2H), 4.32(q, J=8.1 Hz, 2H), 4.83(s, 2H), 5.19(s, 1H), 6.41(d, J=2.5 Hz, 1H), 6.60(dd, J=8.8, 2.5 Hz, 1H), 7.46(d, J=8.8 Hz, 1H).
工程９
化合物６７（１３７ｍｇ、０．２８ｍｍｏｌ）のトルエン（２ｍＬ）溶液に、２－（メタンスルホニル）酢酸（１９１ｍｇ、１．３８ｍｍｏｌ）とＮ，Ｎ’－ジイソプロピルカルボジイミド（０．２２ｍｌ、１．３８ｍｍｏｌ）を室温で加え、３時間撹拌した。室温下、水を加え、酢酸エチルで抽出し、有機層を飽和重層水で洗浄した後、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム-メタノール）により精製し、メタノール-水で粉末化することで、化合物ＩＩ－１２１（８２．４ｍｇ、収率４９％）を得た。
¹H-NMR (CDCl₃) δ: 2.09-2.18(m, 2H), 2.29-2.36(m, 2H), 3.03(d, J=16.3 Hz, 1H), 3.21(s, 3H), 3.31(d, J=16.3 Hz, 1H), 3.99-4.35(m, 10H), 5.92(s, 1H), 6.40(d, J=2.4 Hz, 1H), 6.60(dd, J=8.8, 2.4 Hz, 1H), 7.41(d, J=8.8 Hz, 1H), 9.56(s, 1H). Example 12

Process 1
To compound 51 (1.75 g, 7.69 mmol), (S) -2-methylpropan-2-sulfinamide (1.03 g, 8.45 mmol) and tetraethoxytitanium (3.22 mL, 6 mmol) were added, and the temperature was 100 ° C. Was stirred for two and a half hours. The reaction mixture was diluted with ethyl acetate and water and extracted with ethyl acetate. After washing the organic layer with saturated aqueous sodium chloride solution, the solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to purify compound 59 (1.86 g, yield 73%). Got
¹ H-NMR (CDCl ₃ ) δ: 1.32 (s, 9H), 3.24-3.31 (m, 2H), 3.46-3.53 (m, 2H), 4.28-4.41 (m, 2H), 7.09-7.13 (m, 2H), 7.84 (d, J = 8.4 Hz, 1H).
Step 2
Tetrahydrofuran (15 mL) and methyl acetate (0.72 mL, 9.01 mmol) were added to a 1 mol / L lithium hexamethyldisilazide tetrahydrofuran solution (9.01 mL, 9.01 mmol) at −78 ° C., and the mixture was stirred for 30 minutes. A hexane solution of 1 mol / L titanium chloride triisopropoxide (11.3 mL, 11.3 mmol) was added dropwise to the reaction solution at −78 ° C., and the mixture was stirred for 20 minutes. Then, a solution of compound 59 (1.86 g, 5.63 mmol) in tetrahydrofuran (16 mL) was added dropwise at −78 ° C., and the mixture was stirred for 1 hour. Saturated sodium chloride aqueous solution is added, the mixture is extracted with ethyl acetate, the organic layer is washed with water, the solvent is distilled off under reduced pressure, and the obtained residue is purified by silica gel column chromatography (hexane-ethyl acetate) to purify compound 60. (2.07 g, 77% yield) was obtained.
¹ H-NMR (CDCl ₃ ) δ: 1.22 (s, 9H), 2.22-2.29 (m, 1H), 2.56-2.61 (m, 2H), 2.78 (d, J = 15.8 Hz, 1H), 2.93 (d , J = 15.8 Hz, 1H), 3.71 (s, 3H), 4.20-4.25 (m, 1H), 4.43-4.49 (m, 1H), 5.17 (s, 1H), 7.02-7.05 (m, 2H), 7.11 (d, J = 8.3 Hz, 1H).
Process 3
Bis (pinacolato) diboron (341 mg, 1.34 mmol), potassium acetate (359 mg, 3.66 mmol) and [1,1'-bis] in a 1,4-dioxane (5 mL) solution of compound 60 (512 mg, 1.22 mmol). (Diphenylphosphino) ferrocene] Palladium (II) dichloride dichloromethane adduct (19.9 mg, 0.024 mmol) was added, and the pressure was reduced and nitrogen substitution was repeated 3 times, followed by heating and refluxing for 3 hours. After cooling to room temperature, the insoluble material was filtered through Celite, the solvent was distilled off under reduced pressure, and the obtained residue was diluted with tetrahydrofuran (5 mL), and the mixture was diluted with 30% aqueous hydrogen peroxide solution (277 mg, 2.44 mmol) and 1 mol / L hydroxide. Aqueous sodium solution (0.244 mL, 0.244 mmol) was added, and the mixture was stirred at room temperature for 19 and a half hours. The reaction mixture was treated with sodium thiosulfate pentahydrate (606 mg, 2.44 mmol), extracted with ethyl acetate, the organic layer was washed with water, the solvent was distilled off under reduced pressure, and the obtained residue was hexane-. It was powdered with ethyl acetate to obtain compound 61 (391 mg, yield 94%).
¹ H-NMR (CDCl ₃ ) δ: 1.23 (s, 9H), 2.21-2.28 (m, 1H), 2.45-2.50 (m, 1H), 2.78 (d, J = 15.9 Hz, 1H), 2.99 (d , J = 15.9 Hz, 1H), 3.71 (s, 3H), 4.17-4.22 (m, 1H), 4.43-4.50 (m, 1H), 5.10 (s, 1H), 6.23 (s, 1H), 6.34 ( s, 1H), 6.40 (d, J = 8.3 Hz, 1H), 7.05 (d, J = 8.6 Hz, 1H).
Step 4
A solution of compound 61 (380 mg, 1.11 mmol) in N, N-dimethylformamide (1.5 mL) with 2,2,2-trifluoroethyltrifluoromethanesulfonate (310 mg, 1.34 mmol) and potassium carbonate (310 mg, 1.34 mmol). 185 mg (1,34 mmol) was added, and the mixture was stirred at room temperature for 14 hours, heated to 60 ° C., and further stirred for 2 hours. The reaction mixture was diluted with ethyl acetate and water, the organic layer was washed with water, the solvent was distilled off under reduced pressure, and the obtained residue was mixed with a methanol (2 mL) solution and a 4 mol / L dioxane hydrochloride solution (0.557 mL, 2). .23 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The solvent of the reaction solution was distilled off under reduced pressure, toluene was further added and the solvent was distilled off under reduced pressure, and 2-cyanoacetic acid (161 mg, 1.89 mmol), 1- (3) was added to a dichloromethane (4 mL) solution of the obtained residue. -Dichloromethane) -3-ethylcarbodiimide hydrochloride (363 mg, 1.89 mmol) and triethylamine (0.463 mL, 3.34 mmol) were added, and the mixture was stirred at room temperature for 19 hours. The solvent of the reaction solution was distilled off under reduced pressure, diluted with ethyl acetate and water, the organic layer was washed with water, and the solvent was distilled off under reduced pressure to obtain a crude product of compound 62.
Step 5
60% sodium hydride (270 mg, 6.75 mmol) was added to a solution of the crude product of compound 62 in methanol (4 mL), and the mixture was stirred at room temperature for 5 hours. After adding a 2 mol / L aqueous hydrochloric acid solution (3.34 mL, 6.68 mmol), the solvent was distilled off under reduced pressure, diluted with ethyl acetate and water, the organic layer was washed with water, and then the solvent was distilled off under reduced pressure. The resulting residue was powdered with hexane-ethyl acetate to give compound 63 (324 mg, 82% yield).
¹ H-NMR (DMSO-D ₆ ) δ: 1.99-2.13 (m, 2H), 2.65 (d, J = 17.1 Hz, 1H), 3.19 (d, J = 17.1 Hz, 1H), 4.09-4.17 (m) , 1H), 4.20-4.25 (m, 1H), 4.72 (q, J = 8.9 Hz, 2H), 6.48 (d, J = 2.3 Hz, 1H), 6.64 (dd, J = 8.8, 2.3 Hz, 1H) , 7.41 (d, J = 8.8 Hz, 1H), 7.84 (s, 1H).
Step 6
N, N-dimethylformamide (63.5 mg, 0.869 mmol) and phosphorus oxychloride (133 mg, 0.869 mmol) in a 1,2-dichloroethane (6.2 mL) suspension of compound 63 (308 mg, 0.869 mmol). ) And stirred at room temperature for 18.5 hours. Water was added to the reaction solution, and the precipitated solid was collected by filtration to give compound 64 (312 mg, yield 96%).
¹ H-NMR (CDCl ₃ ) δ: 2.26 (2H, t, J = 5.5 Hz), 3.00 (1H, d, J = 18.8 Hz), 3.44 (1H, d, J = 18.8 Hz), 4.15-4.29 ( 2H, m), 4.30 (1H, d, J = 7.9 Hz), 4.34 (1H, d, J = 7.9 Hz), 5.83 (1H, s), 6.42 (1H, d, J = 2.5 Hz), 6.63 ( 1H, dd, J = 8.8, 2.4 Hz), 7.33 (1H, d, J = 8.8 Hz).
Step 7
Hydrazine monohydrate (225 mg, 3.35 mmol) was added to a solution of compound 64 (500 mg, 1.34 mmol) in tetrahydrofuran (4 mL), and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain compound 65 (432 mg, yield 87%).
[M + H] = 369.00, measurement condition C
Step 8
Compound 66 (324 mg, 1.09 mmol) and cesium carbonate (397 mg, 1.22 mmol) were added to a solution of compound 65 (333 mg, 0.91 mmol) in acetonitrile (2 mL), and the mixture was stirred at 80 ° C. for one and a half hours. Water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) to obtain compound 67 (137 mg, yield 31%).
¹ H-NMR (CDCl ₃ ) δ: 2.14-2.26 (m, 4H), 2.93 (d, J = 16.1 Hz, 1H), 3.21 (d, J = 16.1 Hz, 1H), 3.97-4.03 (m, 4H) ), 4.19-4.21 (m, 2H), 4.32 (q, J = 8.1 Hz, 2H), 4.83 (s, 2H), 5.19 (s, 1H), 6.41 (d, J = 2.5 Hz, 1H), 6.60 (dd, J = 8.8, 2.5 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H).
Step 9
2- (Methanesulfonyl) acetic acid (191 mg, 1.38 mmol) and N, N'-diisopropylcarbodiimide (0.22 ml, 1.38 mmol) at room temperature in a toluene (2 mL) solution of compound 67 (137 mg, 0.28 mmol). And stirred for 3 hours. At room temperature, water was added, the mixture was extracted with ethyl acetate, the organic layer was washed with saturated layered water, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform-methanol) and powdered with methanol-water to obtain Compound II-121 (82.4 mg, yield 49%).
¹ H-NMR (CDCl ₃ ) δ: 2.09-2.18 (m, 2H), 2.29-2.36 (m, 2H), 3.03 (d, J = 16.3 Hz, 1H), 3.21 (s, 3H), 3.31 (d) , J = 16.3 Hz, 1H), 3.99-4.35 (m, 10H), 5.92 (s, 1H), 6.40 (d, J = 2.4 Hz, 1H), 6.60 (dd, J = 8.8, 2.4 Hz, 1H) , 7.41 (d, J = 8.8 Hz, 1H), 9.56 (s, 1H).

工程１
化合物５３（５.５０ｇ、１３．６ｍｍｏｌ）のメタノール（６０ｍＬ）溶液に、４ｍｏｌ／Ｌ塩酸ジオキサン溶液（３．４０ｍＬ、１３．６ｍｍｏｌ）を加え、室温で１時間撹拌した。その後、溶媒を減圧留去した後、得られた残渣をテトラヒドロフラン（６０ｍｌ）に溶解させ、２－シアノ酢酸（２．３１ｇ、２７．２ｍｍｏｌ）、１－エチル－３－（３－ジメチルアミノプロピル）カルボジイミド塩酸塩（５．２２ｇ、２７．２ｍｍｏｌ）とトリエチルアミン（７．５４ｍＬ、５４．４ｍｍｏｌ）を加え、室温で１時間撹拌した。反応液に飽和塩化アンモニウム水溶液を加え、酢酸エチルで抽出し、水で洗浄した後、無水硫酸ナトリウムで乾燥し、溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物６８（４．８０ｇ、収率９６％）を得た。
工程２
化合物６８（４．８０ｇ、１３．１ｍｍol）に、１ｍｏｌ／Ｌソジウムメトキシド メタノール溶液（２６．１ｍＬ、２６．１ｍｍｏｌ）を加え、室温下３時間撹拌した。反応液に１ｍｏｌ／Ｌ塩酸水溶液（１５０ｍＬ）を加え、酢酸エチルで抽出した。有機層を水で洗浄した後、無水硫酸ナトリウムで乾燥した。濃縮後、得られた残渣をヘキサン―酢酸エチルで粉末化させ、化合物６９（３．７５ｇ、８６％）を得た。
¹H NMR (DMSO-d₆) δ: 2.06-2.12(2H, m), 2.71(1H, d, J=17.5 Hz), 3.19(1H, d, J=17.0 Hz), 4.12-4.17(1H, m), 4.22-4.27(1H, m), 7.01(1H, d, J=2.0 Hz), 7.11(1H, dd, J=8.5, 2.0 Hz), 7.42(1H, d, J=8.5 Hz), 7.91(1H, s).
工程３
化合物６９（２．００ｇ、５．９７ｍｍｏｌ）のジクロロエタン（２０ｍＬ）溶液に、ＤＭＦ（４．６４ｍＬ、５９．７ｍｍｏｌ）と塩化ホスホリル（０．６１ｍＬ、６．５６ｍｍｏｌ）を加え、室温で１９時間撹拌した。反応液に水を加え、クロロホルムで抽出し、飽和重層水と飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸マグネシウムで乾燥し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して、ヘキサン―酢酸エチルで粉末化させ、化合物７０（１．０３ｇ、収率４９％）を得た。
¹H-NMR (CDCl₃) δ: 2.27(br-s, 2H), 3.03(d, J=18.6 Hz, 1H), 3.41(d, J=18.8 Hz, 1H), 4.17-4.31(m, 2H), 5.96(s, 1H), 7.07-7.27(m, 3H).
工程４
化合物７０（２５０ｍｇ、０．７１ｍｍｏｌ）のエタノール（５ｍＬ）溶液に、２－ヒドラジニル－５－メチルピリジン塩酸塩（１３５ｍｇ、０．８５ｍｍｏｌ）と炭酸水素ナトリウム（１４８ｍｇ、１．７７ｍｍｏｌ）を加え、７０℃にて１時間半撹拌した。反応液に水を加え、クロロホルムで抽出し、無水硫酸マグネシウムで乾燥し、溶媒を減圧留去し、得られた残渣にジイソプロピルエーテルを加えて粉末化することで、化合物７１（２３７ｍｇ、収率７６％）を得た。
¹H-NMR (CDCl₃) δ: 2.15-2.29(m, 2H), 2.36(s, 3H), 3.03(d, J=16.1 Hz, 1H), 3.24(d, J=16.1 Hz, 1H), 4.22-4.24(m, 2H), 5.23(s, 1H), 7.04(d, J=2.0 Hz, 1H), 7.10(dd, J=8.4, 2.0 Hz, 1H), 7.19(br-s, 2H), 7.42(d, J=8.4 Hz, 1H), 7.61-7.64(m, 1H), 7.76(d, J=8.5 Hz, 1H), 8.19(br-s, 1H).
工程５
化合物７１（１００ｍｇ、０．２３ｍｍｏｌ）のトルエン（２ｍＬ）と水（０．４ｍＬ）溶液に、ポタシウムシクロプロピルトリフルオロボレート（１０１ｍｇ、０．６８ｍｍｏｌ）、［１，１’－ビス（ジ－tert-ブチルホスフィノ）フェロセン］パラジウム（ＩＩ）ジクロリド （０．１４８ｇ、０．２２７ｍｍｏｌ）と炭酸セシウム（０．２２２ｇ、０．６８１ｍｍｏｌ）を加え、１００℃で３時間撹拌した。反応液に水を加え、酢酸エチルで抽出し、有機層を飽和塩化ナトリウム水溶液で洗浄し、無水硫酸マグネシウムで乾燥し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して、ヘキサン―酢酸エチルで粉末化させ、化合物７２（２０．４ｍｇ、収率２２％）を得た。
工程６
化合物７２（２０．４ｍｇ、０．０５１ｍｍｏｌ）のジクロロメタン（１ｍＬ）溶液に、２－（メタンスルホニル）アセチルクロライド（０．２０ｍｍｏｌ）のジクロロメタン（０．３ｍｌ）溶液とピリジン（０．０１６ｍｌ、０．２０ｍｍｏｌ）を０℃で加え、３時間撹拌した。室温下、反応液に水を加え、酢酸エチルで抽出し、硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール、アミノシリカゲル）により精製して、化合物ＩＩ－１６８（１４．２ｍｇ、５４％）を得た。
¹H-NMR (CDCl₃) δ: 0.68-0.72(m, 2H), 0.95-1.00(m, 2H), 1.81-1.88(m, 1H), 2.19-2.28(m, 2H), 2.40(s, 3H), 3.11(d, J=16.3 Hz, 1H), 3.23(s, 3H), 3.42(d, J=16.3 Hz, 1H), 4.14(s, 2H), 4.20-4.22(m, 2H), 5.61(s, 1H), 6.57(d, J=1.8 Hz, 1H), 6.73(dd, J=8.2, 1.8 Hz, 1H), 7.42(d, J=8.2 Hz, 1H), 7.70 (dd, J=8.4, 1.8 Hz, 1H), 7.81(d, J=8.4 Hz, 1H), 8.30(s, 1H), 11.17(s, 1H). Example 13

Process 1
A 4 mol / L dioxane hydrochloride solution (3.40 mL, 13.6 mmol) was added to a methanol (60 mL) solution of compound 53 (5.50 g, 13.6 mmol), and the mixture was stirred at room temperature for 1 hour. Then, after distilling off the solvent under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (60 ml), 2-cyanoacetic acid (2.31 g, 27.2 mmol), 1-ethyl-3- (3-dimethylaminopropyl). Carbodiimide hydrochloride (5.22 g, 27.2 mmol) and triethylamine (7.54 mL, 54.4 mmol) were added, and the mixture was stirred at room temperature for 1 hour. Saturated ammonium chloride aqueous solution is added to the reaction solution, extracted with ethyl acetate, washed with water, dried over anhydrous sodium sulfate, the solvent is distilled off under reduced pressure, and the obtained residue is subjected to silica gel column chromatography (hexane-ethyl acetate). ) To give compound 68 (4.80 g, yield 96%).
Step 2
A 1 mol / L sodium methoxydo methanol solution (26.1 mL, 26.1 mmol) was added to compound 68 (4.80 g, 13.1 mmol), and the mixture was stirred at room temperature for 3 hours. A 1 mol / L hydrochloric acid aqueous solution (150 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then dried over anhydrous sodium sulfate. After concentration, the obtained residue was powdered with hexane-ethyl acetate to give compound 69 (3.75 g, 86%).
¹ H NMR (DMSO-d ₆ ) δ: 2.06-2.12 (2H, m), 2.71 (1H, d, J = 17.5 Hz), 3.19 (1H, d, J = 17.0 Hz), 4.12-4.17 (1H, m), 4.22-4.27 (1H, m), 7.01 (1H, d, J = 2.0 Hz), 7.11 (1H, dd, J = 8.5, 2.0 Hz), 7.42 (1H, d, J = 8.5 Hz), 7.91 (1H, s).
Process 3
DMF (4.64 mL, 59.7 mmol) and phosphoryl chloride (0.61 mL, 6.56 mmol) were added to a solution of compound 69 (2.00 g, 5.97 mmol) in dichloroethane (20 mL), and the mixture was stirred at room temperature for 19 hours. .. Water was added to the reaction solution, the mixture was extracted with chloroform, washed with saturated aqueous layer water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) and powdered with hexane-ethyl acetate to give compound 70 (1.03 g, yield 49%).
¹ H-NMR (CDCl ₃ ) δ: 2.27 (br-s, 2H), 3.03 (d, J = 18.6 Hz, 1H), 3.41 (d, J = 18.8 Hz, 1H), 4.17-4.31 (m, 2H) ), 5.96 (s, 1H), 7.07-7.27 (m, 3H).
Step 4
2-Hydradinyl-5-methylpyridine hydrochloride (135 mg, 0.85 mmol) and sodium hydrogen carbonate (148 mg, 1.77 mmol) were added to a solution of compound 70 (250 mg, 0.71 mmol) in ethanol (5 mL), and the temperature was 70 ° C. Was stirred for one and a half hours. Water was added to the reaction mixture, the mixture was extracted with chloroform, dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and diisopropyl ether was added to the obtained residue to powder the compound 71 (237 mg, yield 76). %) Was obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.15-2.29 (m, 2H), 2.36 (s, 3H), 3.03 (d, J = 16.1 Hz, 1H), 3.24 (d, J = 16.1 Hz, 1H), 4.22-4.24 (m, 2H), 5.23 (s, 1H), 7.04 (d, J = 2.0 Hz, 1H), 7.10 (dd, J = 8.4, 2.0 Hz, 1H), 7.19 (br-s, 2H) , 7.42 (d, J = 8.4 Hz, 1H), 7.61-7.64 (m, 1H), 7.76 (d, J = 8.5 Hz, 1H), 8.19 (br-s, 1H).
Step 5
Potasium cyclopropyltrifluoroborate (101 mg, 0.68 mmol), [1,1'-bis (di-tert-), in a solution of compound 71 (100 mg, 0.23 mmol) in toluene (2 mL) and water (0.4 mL). Butylphosphino) ferrocene] palladium (II) dichloride (0.148 g, 0.227 mmol) and cesium carbonate (0.222 g, 0.681 mmol) were added, and the mixture was stirred at 100 ° C. for 3 hours. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, the organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) and powdered with hexane-ethyl acetate to give compound 72 (20.4 mg, yield 22%).
Step 6
Compound 72 (20.4 mg, 0.051 mmol) in dichloromethane (1 mL), 2- (methanesulfonyl) acetyl chloride (0.20 mmol) in dichloromethane (0.3 ml) and pyridine (0.016 ml, 0.20 mmol). ) Was added at 0 ° C. and stirred for 3 hours. At room temperature, water was added to the reaction mixture, the mixture was extracted with ethyl acetate, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform-methanol, amino silica gel) to obtain compound II-168 (14.2 mg, 54%).
¹ H-NMR (CDCl ₃ ) δ: 0.68-0.72 (m, 2H), 0.95-1.00 (m, 2H), 1.81-1.88 (m, 1H), 2.19-2.28 (m, 2H), 2.40 (s, 3H), 3.11 (d, J = 16.3 Hz, 1H), 3.23 (s, 3H), 3.42 (d, J = 16.3 Hz, 1H), 4.14 (s, 2H), 4.20-4.22 (m, 2H), 5.61 (s, 1H), 6.57 (d, J = 1.8 Hz, 1H), 6.73 (dd, J = 8.2, 1.8 Hz, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.70 (dd, J = 8.4, 1.8 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 8.30 (s, 1H), 11.17 (s, 1H).

工程１
（Ｒ）－２－メチルプロパン－２－スルフィンアミド（６３１ｍｇ、５．２１ｍｍｏｌ）のトルエン（２．５ｍＬ）溶液に、テトラエトキシチタン（０．６５４ｍＬ、３．１２ｍｍｏｌ）を加え、化合物７３（３８４ｍｇ、２．０８ｍｍｏｌ）のトルエン（２．５ｍＬ）溶液を加え、１００℃で３時間撹拌した。反応液に、室温下クエン酸水溶液と酢酸エチル加えて、不溶物を濾過し、酢酸エチルで抽出した。有機層を飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物７４（４２８ｍｇ、収率７２％）を得た。
¹H-NMR (CDCl₃) δ: 1.32(s, 9H), 3.31-3.38(m, 1H), 3.45-3.52(m, 1H), 4.27-4.33(m, 1H), 4.36-4.41(m, 1H), 6.43-6.49(m, 2H).
工程２
１ｍｏｌ／Ｌリチウムヘキサメチルジシラジド テトラヒドロフラン溶液（２．２３ｍＬ、２．２３ｍｍｏｌ）に、テトラヒドロフラン（１ｍＬ）と酢酸メチル（０．１７８ｍＬ、２．２３ｍｍｏｌ）を－７８℃で加え、１時間撹拌した。その後、１ｍｏｌ／Ｌ塩化チタントリイソプロポキド ヘキサン溶液（２．９８ｍＬ、２．９８ｍｍｏｌ）を－７８℃で滴下し、３０分間撹拌した。その後、化合物７４（４２８ｍｇ、１．４９ｍｍｏｌ）のテトラヒドロフラン（１ｍＬ）溶液を、－７８℃で滴下し、４時間撹拌した。反応液に１０％のクエン酸水溶液とロッシェル塩を加え、室温に昇温して１２時間撹拌し、酢酸エチルで抽出し、有機層を飽和重層水と飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製して化合物７５（３０５ｍｇ、収率５７％）を得た。
¹H-NMR (CDCl₃) δ: 1.22(s, 9H), 2.19-2.27(m, 1H), 2.45-2.49(m, 1H), 2.74(d, J=15.9 Hz, 1H), 3.40(d, J=15.9 Hz, 1H), 3.70(s, 3H), 4.19-4.24(m, 1H), 4.51-4.57(m, 1H), 5.02(s, 1H), 6.36-6.47(m, 2H).
工程３
化合物７５（３０５ｍｇ、０．８５ｍｍｏｌ）のメタノール（２．６ｍＬ）溶液に、４ｍｏｌ／Ｌ塩酸ジオキサン溶液（０．４４ｍＬ、１．７７ｍｍｏｌ）を加え、０℃で１時間撹拌した。反応液の溶媒を減圧留去した後、得られた残渣をテトラヒドロフラン（２．５ｍｌ）に溶解させ、２－シアノ酢酸（１０８ｍｇ、１．２７ｍｍｏｌ）、ＨＡＴＵ（４８２ｍｇ、１．２７ｍｍｏｌ）とトリエチルアミン（０．２９ｍＬ、２．１１ｍｍｏｌ）を加え、室温で４時間撹拌した。反応液に水を加え、酢酸エチルで抽出し、飽和重層水と飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸ナトリウムで乾燥し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、ヘキサン―酢酸エチルで粉末化し、化合物７６（１７０ｍｇ、収率６２％）を得た。
¹H-NMR (CDCl₃) δ: 2.08-2.14(m, 1H), 2.83-2.90(m, 1H), 2.96(d, J=14.7 Hz, 1H), 3.26-3.33(m, 3H), 3.75(s, 3H), 4.13-4.18(m, 1H), 4.27-4.33(m, 1H), 6.35-6.44(m, 2H), 7.51(s, 1H).
工程４
化合物７６（３９３ｍｇ、１．２１ｍｍol）のメタノール（４ｍＬ）とテトラヒドロフラン（１ｍＬ）溶液に、１ｍｏｌ／Ｌソジウムメトキシド メタノール溶液（２．６ｍＬ、２．６ｍｍｏｌ）を加え、室温下７時間撹拌した。反応液に２ｍｏｌ／Ｌの塩酸水溶液（１．３ｍＬ）を加え、濃縮後得られた残渣にメタノールを加え、不溶物を濾過により除き、溶媒を減圧留去した。得られた残渣に酢酸エチルを加えて粉末化させ、化合物７７（２１３ｍｇ、６０％）を得た。
¹H-NMR (DMSO-D₆) δ: 2.07-2.17(m, 2H), 2.72(d, J=17.7 Hz, 1H), 3.19(d, J=17.7 Hz, 1H), 4.10-4.22(m, 2H), 6.61(br-d, J=10.2 Hz, 1H), 6.78-6.84(m, 1H), 7.89(s, 1H).
工程５
化合物７７（１．０ｇ、３．４２ｍｍｏｌ）のジクロロエタン（１０ｍＬ）溶液に、ＤＭＦ（２．６６ｍＬ、３４．２ｍｍｏｌ）と塩化ホスホリル（０．３５ｍＬ、３．７６ｍｍｏｌ）を加え、室温で２０時間撹拌した。反応液に水を加え、クロロホルムで抽出し、飽和重層水と飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸マグネシウムで乾燥し、溶媒を減圧留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（ヘキサン－酢酸エチル）により精製し、化合物７８（４１３ｍｇ、収率３９％）を得た。
［Ｍ＋Ｈ］＝３１０．９５、測定条件Ｃ
工程６
化合物７８（５０ｍｇ、０．１６ｍｍｏｌ）のエタノール（１ｍＬ）溶液に、２－ヒドラジニル－５－メチルピリジン塩酸塩（３０．８ｍｇ、０．１９ｍｍｏｌ）と炭酸水素ナトリウム（３４ｍｇ、０．４０ｍｍｏｌ）を加え、８０℃にて２時間撹拌した。反応液に水を加え、酢酸エチルで抽出し、飽和塩化ナトリウム水溶液で洗浄した後、無水硫酸マグネシウムで乾燥し、溶媒を減圧留去した。得られた残渣をジクロロメタン（１．０ｍＬ）に溶解し、２－（メタンスルホニル）アセチルクロライド（０．６４ｍｍｏｌ）のジクロロメタン（１．０ｍｌ）溶液とピリジン（０．０５２ｍｌ、０．６４ｍｍｏｌ）を０℃で加え、３時間撹拌した。室温下、水を加え、酢酸エチルで抽出し、硫酸マグネシウムで乾燥した。溶媒を減圧留去し、得られた残渣をシリカゲルカラムクロマトグラフィー（クロロホルム‐メタノール、アミノシリカゲル）により精製して、ヘキサン―酢酸エチルで粉末化させることで化合物ＩＩ－２０３（５２．７ｍｇ、４１％）を得た。
¹H-NMR (CDCl₃) δ: 2.19-2.26(m, 1H), 2.32-2.40(m, 4H), 2.99(d, J=16.2 Hz, 1H), 3.22(s, 3H), 3.81(d, J=16.2 Hz, 1H), 4.15-4.20(m, 4H), 5.77(s, 1H), 6.47-6.52(m, 2H), 7.69-7.71(m, 1H), 7.81(d, J=8.3 Hz, 1H), 8.30(br-s, 1H). Example 14

Process 1
To a solution of (R) -2-methylpropane-2-sulfinamide (631 mg, 5.21 mmol) in toluene (2.5 mL), tetraethoxytitanium (0.654 mL, 3.12 mmol) was added, and compound 73 (384 mg, A 2.08 mmol) toluene (2.5 mL) solution was added and the mixture was stirred at 100 ° C. for 3 hours. An aqueous citric acid solution and ethyl acetate were added to the reaction solution at room temperature, the insoluble material was filtered off, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 74 (428 mg, yield 72%).
¹ H-NMR (CDCl ₃ ) δ: 1.32 (s, 9H), 3.31-3.38 (m, 1H), 3.45-3.52 (m, 1H), 4.27-4.33 (m, 1H), 4.36-4.41 (m, 1H), 6.43-6.49 (m, 2H).
Step 2
Tetrahydrofuran (1 mL) and methyl acetate (0.178 mL, 2.23 mmol) were added to a solution of 1 mol / L lithium hexamethyldisilazide in tetrahydrofuran (2.23 mL, 2.23 mmol) at −78 ° C., and the mixture was stirred for 1 hour. Then, a 1 mol / L titanium chloride triisopropoxide hexane solution (2.98 mL, 2.98 mmol) was added dropwise at −78 ° C., and the mixture was stirred for 30 minutes. Then, a solution of compound 74 (428 mg, 1.49 mmol) in tetrahydrofuran (1 mL) was added dropwise at −78 ° C., and the mixture was stirred for 4 hours. A 10% aqueous citric acid solution and a Rochelle salt are added to the reaction solution, the temperature is raised to room temperature, the mixture is stirred for 12 hours, extracted with ethyl acetate, and the organic layer is washed with saturated aqueous layer water and saturated aqueous sodium chloride solution, and then anhydrous sulfuric acid. Dry with magnesium. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 75 (305 mg, yield 57%).
¹ H-NMR (CDCl ₃ ) δ: 1.22 (s, 9H), 2.19-2.27 (m, 1H), 2.45-2.49 (m, 1H), 2.74 (d, J = 15.9 Hz, 1H), 3.40 (d , J = 15.9 Hz, 1H), 3.70 (s, 3H), 4.19-4.24 (m, 1H), 4.51-4.57 (m, 1H), 5.02 (s, 1H), 6.36-6.47 (m, 2H).
Process 3
A 4 mol / L dioxane hydrochloride solution (0.44 mL, 1.77 mmol) was added to a solution of compound 75 (305 mg, 0.85 mmol) in methanol (2.6 mL), and the mixture was stirred at 0 ° C. for 1 hour. After distilling off the solvent of the reaction solution under reduced pressure, the obtained residue was dissolved in tetrahydrofuran (2.5 ml), and 2-cyanoacetic acid (108 mg, 1.27 mmol), HATU (482 mg, 1.27 mmol) and triethylamine (0) were dissolved. .29 mL, 2.11 mmol) was added, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, washed with saturated aqueous layered water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) and powdered with hexane-ethyl acetate to give compound 76 (170 mg, yield 62%).
¹ H-NMR (CDCl ₃ ) δ: 2.08-2.14 (m, 1H), 2.83-2.90 (m, 1H), 2.96 (d, J = 14.7 Hz, 1H), 3.26-3.33 (m, 3H), 3.75 (s, 3H), 4.13-4.18 (m, 1H), 4.27-4.33 (m, 1H), 6.35-6.44 (m, 2H), 7.51 (s, 1H).
Step 4
A 1 mol / L sodium methoxydo methanol solution (2.6 mL, 2.6 mmol) was added to a solution of compound 76 (393 mg, 1.21 mmol) in methanol (4 mL) and tetrahydrofuran (1 mL), and the mixture was stirred at room temperature for 7 hours. A 2 mol / L hydrochloric acid aqueous solution (1.3 mL) was added to the reaction solution, methanol was added to the residue obtained after concentration, the insoluble material was removed by filtration, and the solvent was distilled off under reduced pressure. Ethyl acetate was added to the obtained residue and powdered to obtain compound 77 (213 mg, 60%).
¹ H-NMR (DMSO-D ₆ ) δ: 2.07-2.17 (m, 2H), 2.72 (d, J = 17.7 Hz, 1H), 3.19 (d, J = 17.7 Hz, 1H), 4.10-4.22 (m) , 2H), 6.61 (br-d, J = 10.2 Hz, 1H), 6.78-6.84 (m, 1H), 7.89 (s, 1H).
Step 5
DMF (2.66 mL, 34.2 mmol) and phosphoryl chloride (0.35 mL, 3.76 mmol) were added to a solution of compound 77 (1.0 g, 3.42 mmol) in dichloroethane (10 mL), and the mixture was stirred at room temperature for 20 hours. .. Water was added to the reaction solution, the mixture was extracted with chloroform, washed with saturated aqueous layer water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain compound 78 (413 mg, yield 39%).
[M + H] = 310.95, measurement condition C
Step 6
To a solution of compound 78 (50 mg, 0.16 mmol) in ethanol (1 mL) was added 2-hydrazinyl-5-methylpyridine hydrochloride (30.8 mg, 0.19 mmol) and sodium hydrogen carbonate (34 mg, 0.40 mmol). The mixture was stirred at 80 ° C. for 2 hours. Water was added to the reaction solution, the mixture was extracted with ethyl acetate, washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was dissolved in dichloromethane (1.0 mL), and a solution of 2- (methanesulfonyl) acetyl chloride (0.64 mmol) in dichloromethane (1.0 ml) and pyridine (0.052 ml, 0.64 mmol) were added at 0 ° C. And stirred for 3 hours. At room temperature, water was added, the mixture was extracted with ethyl acetate, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (chloroform-methanol, amino silica gel) and powdered with hexane-ethyl acetate to obtain Compound II-203 (52.7 mg, 41%). ) Was obtained.
¹ H-NMR (CDCl ₃ ) δ: 2.19-2.26 (m, 1H), 2.32-2.40 (m, 4H), 2.99 (d, J = 16.2 Hz, 1H), 3.22 (s, 3H), 3.81 (d) , J = 16.2 Hz, 1H), 4.15-4.20 (m, 4H), 5.77 (s, 1H), 6.47-6.52 (m, 2H), 7.69-7.71 (m, 1H), 7.81 (d, J = 8.3) Hz, 1H), 8.30 (br-s, 1H).

The compounds shown below were also synthesized in the same manner.

It should be noted that II-275 and II-276 are optically active compounds in which the stereochemistry of sulfoxyimine is different from each other, although the structure of the stereochemistry has not been determined.

The physical data of each compound is shown below.
In the table, "RT" indicates the retention time (minutes) in LC / MS (liquid chromatography / mass spectrometry), and "MS" indicates the mass (M + H) in LC / MS. The term "LCMS Method" represents any of the following measurement conditions for LC / MS.
[Measurement condition A]
Column: ACQUITY UPLC® BEH C18 (1.7 μm id2.1x50 mm) (Waters)
Flow velocity: 0.8 mL / min UV detection wavelength: 254 nm
Mobile phase: [A] is a 0.1% formic acid-containing aqueous solution [B] is a 0.1% formic acid-containing acetonitrile solution. After linear gradient of 5% -100% solvent [B] for 3.5 minutes, 0. The 100% solvent [B] was maintained for 5 minutes.
[Measurement condition B]
Column: Shim-pack XR-ODS (2.2μm id50x3.0mm) (Shimadzu)
Flow velocity: 1.6 mL / min UV detection wavelength: 254 nm;
Mobile phase: [A] is a 0.1% formic acid-containing aqueous solution, [B] is a 0.1% formic acid-containing acetonitrile solution Granant: 10% -100% solvent [B] is linearly gradient in 3 minutes. The 100% solvent [B] was maintained for 5 minutes.
[Measurement condition C]
Column: ACQUITY UPLC® BEH C18 (1.7 μm id2.1x50 mm) (Waters)
Flow velocity: 0.55 mL / min UV detection wavelength: 254 nm
Mobile phase: [A] is an aqueous solution containing 0.1% formic acid, [B] is an acetonitrile solution containing 0.1% formic acid. The 100% solvent [B] was maintained for 5 minutes.
[Measurement condition D]
Column: Shim-pack XR-ODS (2.2μm id50x3.0mm) (Shimadzu)
Flow velocity: 1.6 mL / min UV detection wavelength: 254 nm
Mobile phase: [A] is a 0.1% formic acid-containing aqueous solution, [B] is a 0.1% formic acid-containing acetonitrile solution Granant: 10% -100% solvent [B] is linearly gradient in 8 minutes. The 100% solvent [B] was maintained for 5 minutes.

The NMR analysis obtained in each example was performed at 300 MHz and measured using DMSO-d ₆ and CDCl ₃ .

Hereinafter, examples of biological tests of the compound according to the present invention will be described.

Preparation Example 1 (Preparation of recombinant human MGAT2)
A full-length human MGAT2 gene with Flag-tag added to the N-terminal was inserted into pFastBac (manufactured by Invitrogen). Recombinant baculovirus was prepared and infected with Sf-9 cells according to the protocol of the Bac-to-Bac baculovirus expression system (manufactured by Invitrogen). The collected cells were crushed by ultrasonic waves, and then the membrane fraction was collected by centrifugation. Expression was confirmed by Western blotting analysis with an anti-Flag antibody, and a recombinant human MGAT2 enzyme solution was used.

Test Example 1 (Measurement of human MGAT2 inhibitory activity)
An assay buffer (100 mmol / L phosphate buffer (pH 7.4) containing 2 mmol / l DTT) was placed on a 384-well microplate made of Corning polystyrene, to which 0.2 μL of DMSO solution of each compound according to the present invention was dispensed. ), Add 5 μL of the enzyme solution and 5 μL of the substrate solution (100 mmol / L phosphate buffer (pH 7.4), 30 μmol / L 2-Oleoylglycerol, 10 μmol / L Oleoyl-CoA), stir and centrifuge, and then wet the box. Incubated in the room for 1 hour at room temperature. After the enzymatic reaction, the reaction was stopped by adding 50 μL of a stop solution containing Internal Standard (IS) (containing 0.2 μmol / L Diolein-d5, 0.4% formic acid and 50% isopropanol), and the reaction was stopped by adding 50 μL to a plate manufactured by Shimadzu GLC. After sealing, stirring and centrifugation were performed, and measurements were performed by electrospray ionization using a RapidFire 360 and an Agilent 6550 Q-TOF mass spectrometer. The reaction product (P) Diolein of 2-Oleoylglycerol, which is a substrate, and the ammonium adduct ion of IS were detected, and the peak intensity ratio P / IS was calculated using the peak height to evaluate the inhibitory activity. The inhibitory activity is defined as Control (+) / Control (-) with and without enzyme addition, respectively, and the inhibition rate is 0% and 100%, respectively, and the peak intensity ratio P / when the compound according to the present invention is added. Using IS as a sample, it was calculated by TIBCO Spotfire (manufactured by TIBCO Software) by the following formula.
Inhibitory activity (%) = [1-{Sample-Control (-)} / {Control (+)-Control (-)}] * 100
The following table shows the results of the inhibitory activity of each compound according to the present invention. IC ₅₀ (nM) in the table indicates a concentration exhibiting 50% enzyme inhibition.

Test Example 2 (Metabolism Stability Test)
A commercially available pooled human liver microsome was reacted with the compound according to the present invention for a certain period of time, the residual rate was calculated by comparing the reaction sample and the unreacted sample, and the degree to which the compound according to the present invention was metabolized in the liver was evaluated.

In 0.2 mL buffer (50 mmol / L Tris-HCl pH 7.4, 150 mmol / L potassium chloride, 10 mmol / L magnesium chloride) containing 0.5 mg protein / mL of human liver microsomes in the presence of 1 mmol / L NADPH The reaction was carried out at 37 ° C. for 0 or 30 minutes (oxidative reaction). After the reaction, 50 μL of the reaction solution was added to 100 μL of a methanol / acetonitrile = 1/1 (v / v) solution, mixed, and centrifuged at 3000 rpm for 15 minutes. The compound according to the present invention in the centrifugal supernatant was quantified by LC / MS / MS, and the residual amount of the compound according to the present invention after the reaction was calculated with the compound amount at the time of 0 minute reaction as 100%.
(Results) The residual rate at a compound concentration of 0.5 μmol / L is shown.

Test Example 3 (Solubility Test)
The solubility of the compound according to the present invention was determined under the condition of adding 1% DMSO. A 10 mmol / L compound solution was prepared by DMSO, and 6 μL of the compound solution according to the present invention was mixed with a pH 6.8 artificial intestinal solution (0.2 mol / L potassium dihydrogen phosphate test solution 250 mL, 0.2 mol / L NaOH test solution 118 mL, and water). It was added to 594 μL (which was 1000 mL). After allowing to stand at 25 ° C. for 16 hours, the mixed solution was suction-filtered. The filtrate was diluted 2-fold with methanol / water = 1/1 (V / V), and the concentration in the filtrate was measured by HPLC or LC / MS / MS by the absolute calibration curve method.
(result)

Test Example 4 (phototoxicity test)
As an in vitro phototoxicity test, an erythrocyte photohemolysis test (Wolfgang JW Pepe et al., ATLA29, 145-162, 2001), which is an evaluation method using the action on biological membranes and photoperoxidation as an index, was performed. In this method, a mixed solution (concentration: 0.1 to 0.0008%) in which 2.5% (v / v) of sheep erythrocyte solution is added to the preparation solution of the compound according to the present invention using dimethylswoxide as a medium. ) Was used. Two microplates to which this mixed solution was added were prepared, and one microplate was irradiated with light in the UVA and UVB regions using an ultraviolet fluorescent lamp (GL20SE lamp, Sankyo Electric and FL20S-BLB lamp, Panasonic) (10J / After performing centrifuge with a microplate not irradiated with light (cm ² , 290 to 400 nm), the absorbance of the supernatant (540 nm or 630 nm) was measured. In order to obtain two indexes (action on biological membrane and photoperoxidation) used for determining phototoxicity, the absorbance in the medium was subtracted from the absorbance obtained from the compound according to the present invention, both with and without light irradiation. The values were calculated and used for subsequent calculations. For the action on the biological membrane, the photohemolysis rate was obtained from the difference between the light-irradiated and unirradiated absorbances (540 nm), and for the photoperoxidation, the amount of change in the light-irradiated and unirradiated absorbances (630 nm) was determined. In the calculation of the photohemolysis rate, the absorbance (540 nm) obtained from the 2.5% (v / v) sheep red blood cell solution forcibly hemolyzed with distilled water was used as the standard for the photohemolysis rate of 100%. The case where the photohemolysis rate is less than 10% and the amount of change in absorbance at 630 nm is less than 0.05 is defined as (-), and the case where the photohemolysis rate is 10% or more and the amount of change in absorbance at 630 nm is 0. The case of 05 or more was defined as (+).
(result)
Compound I-34: (-)

Test Example 5 (cell damage test)
Using Toxinsight (Thermofisher Scientific), which is a cell image analyzer, the number of cells after exposure to the compound was automatically measured, and the cytotoxicity of the compound according to the present invention was evaluated.
HepG2 cells (derived from human liver cancer cells) were seeded on a 384-well plate at 60000 cells / mL, and a compound solution was added to each well 24 hours later. As the compound solution, a DMSO solution containing the compound according to the present invention (maximum concentration is set to 50 μmol / L, diluted in 5 steps at a 2-fold common ratio, minimum concentration is about 3.1 μmol / L), and DMSO only as a negative control. A solution and a camptothecin solution were used as a positive control. A DMSO solution, a negative control solution, or a positive control solution of the compound according to the present invention was added to each well. After 71 hours, Hoechst 33342 solution diluted with dalvecolinic acid buffer (D-PBS) to a final concentration of 1 μg / mL was added to each well and the nucleus was placed in a 5% CO ₂ incubator at 37 ° C. for 1 hour. Staining was performed. After staining, the cells were fixed in a CO ₂ incubator at 37 ° C. for 20 minutes with 4% paraformaldehyde. Finally, after washing with D-PBS three times, the number of fluorescently colored nuclei per well was counted using Toxinsight (Thermofisher Scientific). Four wells were provided per concentration, and the average value and variation (SD) of the number of nuclei (the number of cells in which no disorder was observed) in the four wells were calculated. Calculate the compound exposure concentration (IC ₅₀ ) in which the mean value is reduced by 50% or more from the mean value of the negative control group as compared with the negative control group. It was judged that the smaller the IC ₅₀ value, the higher the risk of cytotoxicity.

Test Example 6 (anti-obesity effect test)
The anti-obesity effect of the compounds of Examples was examined in C57BL / 6j mice (DIO mice) fed a high-fat diet (TestDiet; 58Y1).
A 5-week-old male C57BL / 6j (Claire Japan) was purchased, fed with a high-fat diet under a 12-hour light-dark cycle, and bred for 4 weeks to prepare DIO mice. The vehicle (0.5% HPMC) was administered twice daily from 3 weeks before compound administration. Randomization was performed according to changes in body weight and food intake during the acclimatization period, and grouping was performed (n = 7). From Day 1 to Day 28, forced trans-law administration of the example compound or vehicle (0.5% HPMC) was performed twice a day. Body weight and food intake were measured daily. The patient was dissected on Day28, the epididymal fat weight was measured, and the collected blood was biochemically examined.
As a result of the test, a mouse to which the compound according to the present invention was administered was found to have a clear effect of suppressing weight gain as compared with a mouse to which the compound was not administered.

試験の結果、本発明に係る化合物を投与されたマウスは、化合物の投与量依存的に脂質吸収の抑制効果が認められた。
以上の結果から、本発明の医薬組成物は、肥満症、メタボリックシンドローム、高脂血症、高中性脂肪血症、高ＶＬＤＬ血症、高脂肪酸血症、糖尿病または動脈硬化症の予防剤、および／または治療剤として有用であることが示された。 Test Example 7 (lipid absorption inhibitory action)
Male C57BL / 6j mice (7-8 weeks old) fasted 17 hours before administration of corn oil were forced to use 0.5% hydroxypropylmethylcellulose (0.5% HPMC aqueous solution) or a suspended compound in this aqueous solution. Orally administered. After 13 hours, a lipoprotein lipase inhibitor (Pluronic F-127: Sigma, 50 mg / mL) was intraperitoneally administered at a dose of 10 mL / kg to eliminate the effects of blood triglyceride (TG) clearance, 15 minutes later. Corn oil (5 uCi / mL) containing 14C-labeled triolein was administered orally at a dose of 200 uL / mouse. Blood was collected from the inferior vena cava under anesthesia 4 hours after administration of corn oil, and blood was collected in a tube containing heparin. Plasma was separated by centrifugation, 20 μL of which was mixed well with 200 uL of scintillation cocktail, and radioactivity was measured using a liquid scintillation counter. The rate of decrease in plasma radioactivity in the compound-administered group with respect to the plasma radioactivity in the 0.5% HPMC-administered group was defined as the lipid absorption suppression rate (%).
(result)

As a result of the test, the mice to which the compound according to the present invention was administered were found to have an inhibitory effect on lipid absorption depending on the dose of the compound.
From the above results, the pharmaceutical composition of the present invention is a preventive agent for obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, hyperfatty acidemia, diabetes or arteriosclerosis, and / Or has been shown to be useful as a therapeutic agent.

Test Example 8 (CYP inhibition test)
Using commercially available pooled human liver microsomes, O-deethylation of 7-ethoxyresorphin (CYP1A2), methyl of tolubutamide, as a typical substrate metabolic reaction of the major human CYP5 molecular species (CYP1A2, 2C9, 2C19, 2D6, 3A4). -Hydration (CYP2C9), 4'-hydroxylation of mephenitoin (CYP2C19), O demethylation of dexstrometolphan (CYP2D6), hydroxylation of terfenazine (CYP3A4) are used as indicators, and the amount of each metabolite produced is this. The degree of inhibition by the compound according to the invention was evaluated.
The reaction conditions are as follows: substrate, 0.5 μmol / L ethoxyresorphin (CYP1A2), 100 μmol / L tolubutamide (CYP2C9), 50 μmol / L S-mephenytoin (CYP2C19), 5 μmol / L dextrometholphan (CYP2D6), 1 μmol / L terphenadine (CYP3A4); reaction time, 15 minutes; reaction temperature, 37 ° C; enzyme, pooled human liver microsome 0.2 mg protein / mL; compound concentration according to the present invention 1, 5, 10, 20 μmol / L (4). point).
As a reaction solution, add 5 kinds of substrates, human liver microsomes, and the compound according to the present invention to a 96-well plate in 50 mmol / L Hepes buffer with the above composition, and add NADPH, which is a coenzyme, as an index. A metabolic reaction was initiated. After reacting at 37 ° C. for 15 minutes, the reaction was stopped by adding a methanol / acetonitrile = 1/1 (V / V) solution. After centrifugation at 3000 rpm for 15 minutes, resorphin (CYP1A2 metabolite) in the centrifugal supernatant was quantified with a fluorescent multi-label counter or LC / MS / MS, and tolubutamide hydroxide (CYP2C9 metabolite), mephenytoin 4'hydroxylizer. The body (CYP2C19 metabolite), dextrolphan (CYP2D6 metabolite), and terfenazine alcohol (CYP3A4 metabolite) were quantified by LC / MS / MS.
The control (100%) was obtained by adding only DMSO, which is a solvent in which the drug was dissolved, to the reaction system, the residual activity (%) was calculated, and the IC ₅₀ was calculated by reverse estimation using a logistic model using the concentration and suppression rate. Calculated.
(result)
Compound II-103: 5 types> 20 μmol / L

Test Example 9 (BA test)
Examination of oral absorbability Experimental materials and methods (1) Animals used: Mice or SD rats were used.
(2) Breeding conditions: Mice or SD rats were allowed to freely ingest solid feed and sterile tap water.
(3) Dosage and grouping settings: Oral administration and intravenous administration were administered at predetermined doses. The group was set as follows. (Dose may change for each compound)
Oral administration 1 to 30 mg / kg (n = 2 to 3)
Intravenous administration 0.5-10 mg / kg (n = 2-3)
(4) Preparation of administration solution: Oral administration was administered as a solution or suspension. Intravenous administration was solubilized.
(5) Administration method: Oral administration was forcibly administered intragastrically by an oral sonde. Intravenous administration was performed from the tail vein or femoral vein by a syringe equipped with an injection needle.
(6) Evaluation item: Blood was collected over time, and the concentration of the compound according to the present invention in plasma was measured using LC / MS / MS.
(7) Statistical analysis: For the change in plasma concentration of the compound according to the present invention, the area under the plasma concentration-time curve (AUC) was calculated using the nonlinear least squares program WinNonlin (registered trademark), and the oral administration group and intravenous. The bioavailability (BA) of the compound according to the present invention was calculated from the AUC of the internal administration group.
(result)
Compound II-94: 73%

Test Example 10 (CYP3A4 (MDZ) MBI test)
It is a test for evaluating the mechanism based indication (MBI) ability from the enhancement by a metabolic reaction with respect to the inhibition of CYP3A4 of the compound which concerns on this invention. CYP3A4 inhibition was evaluated using pooled human liver microsomes using the 1-hydroxylation reaction of midazolam (MDZ) as an index.
Reaction conditions are as follows: substrate, 10 μmol / L MDZ; pre-reaction time, 0 or 30 minutes; reaction time, 2 minutes; reaction temperature, 37 ° C; pooled human liver microsomes, 0.5 mg / mL during pre-reaction, reaction 0.05 mg / mL (at 10-fold dilution); concentrations 1, 5, 10 and 20 μmol / L (4 points) at the time of compound prereaction according to the present invention.
Add pooled human liver microsomes and a compound solution according to the present invention to a 96-well plate as a pre-reaction solution in K-Pi buffer (pH 7.4) with the above pre-reaction composition, and add the substrate and K- to another 96-well plate. Part of it was transferred so that it was diluted 1/10 with Pi buffer, and the coenzyme NADPH was added to start the reaction as an index (no pre-reaction), and after a predetermined time reaction, methanol / acetonitrile. The reaction was stopped by adding = 1/1 (V / V) solution. In addition, NADPH is added to the remaining pre-reaction solution to start the pre-reaction (pre-reaction is present), and after the pre-reaction for a predetermined time, another plate is diluted 1/10 with the substrate and K-Pi buffer. The reaction was started by shifting the part and using it as an index. After the reaction for a predetermined time, the reaction is stopped by adding a methanol / acetonitrile = 1/1 (V / V) solution. After centrifuging the plate subjected to each index reaction at 3000 rpm for 15 minutes, 1-hydroxyl midazolam in the centrifugal supernatant was quantified by LC / MS / MS.
The control (100%) was obtained by adding only DMSO, which is a solvent in which the compound according to the present invention was dissolved, to the reaction system, and the residual activity (%) when the compound according to the present invention was added at each concentration was calculated. ICs were calculated by inverse estimation with a logistic model using the concentration and inhibition rate. The IC of Preincubation 0 min / IC of Preincubaion 30 min was set as the Shifted IC value, and if the Shifted IC was 1.5 or more, it was set as Positive, and if the Shifted IC was 1.0 or less, it was set as Negative.
(result)
Compound II-103: Negative

Test Example 11 (powder solubility test)
Put an appropriate amount of the compound according to the present invention in an appropriate container, and add JP-1 solution (2.0 g of sodium chloride, 7.0 mL of hydrochloric acid and water to make 1000 mL) and JP-2 solution (pH 6.8) in each container. Add 500 mL of water to 500 mL of phosphate buffer) and 200 μL of 20 mmol / L sodium taurocholate (TCA) / JP-2 solution (add JP-2 solution to 1.08 g of TCA to make 100 mL). When the entire amount was dissolved after the test solution was added, the compound according to the present invention was added as appropriate. After sealing and shaking at 37 ° C. for 1 hour, the mixture is filtered, and 100 μL of methanol is added to 100 μL of each filtrate for 2-fold dilution. The dilution ratio is changed as necessary. After checking for air bubbles and precipitates, the mixture was sealed and shaken. The compound according to the present invention was quantified by the absolute calibration curve method using HPLC.
(result)
Compound II-94: JP-2 solution: 3.4 μmol / L

Test Example 12 (Fructuation Ames test)
The mutagenicity of the compound according to the present invention was evaluated.
20 μL of cryopreserved Salmonella typhimurium TA98 strain, TA100 strain was inoculated into 10 mL liquid nutrient medium (2.5% Oxoid nutrient blood No. 2) and cultured at 37 ° C. for 10 hours before shaking. For the TA98 strain, 8.0 mL of the bacterial solution was centrifuged (2000 × g, 10 minutes) to remove the culture solution. 8.0 mL Micro F buffer (K ₂ HPO ₄ : 3.5 g / L, KH ₂ PO ₄ : 1 g / L, (NH ₄ ) ₂ SO ₄ : 1 g / L, trisodium citrate dihydrate: Suspend the bacteria in 0.25 g / L, _Л4.7H20 : 0.1 g / L) and add 120 mL of Exposure medium (biotin: ₈ μg / mL, histidine: 0.2 μg / mL, glucose: 8 mg / mL). Included in MicroF buffer). The TA100 strain was added to 120 mL of Exposure medium with respect to 3.1 mL of the bacterial solution to prepare a test bacterial solution. The compound DMSO solution according to the present invention (diluted from the maximum dose of 50 mg / mL in several steps at a common ratio of 2 to 3 times), DMSO as a negative control, and 50 μg / mL for TA98 strain under non-metabolic activation conditions as a positive control. 4-Nitroquinolin-1-oxide DMSO solution, 0.25 μg / mL 2- (2-furyl) -3- (5-nitro-2-furyl) acrylamide DMSO solution for TA100 strain, metabolic activation conditions In the case of TA98 strain, 40 μg / mL 2-aminoanthracene DMSO solution, and for TA100 strain, 20 μg / mL 2-aminoanthracene DMSO solution, 12 μL and 588 μL of the test bacterial solution (498 μL of the test bacterial solution under metabolic activation conditions). And S9 mix (90 μL of mixed solution) were mixed, and the mixture was shake-cultured at 37 ° C. for 90 minutes. A MicroF buffer solution containing 230 μL of the bacterial solution exposed to the compound according to the present invention containing an indicator medium (biotin: 8 μg / mL, histidine: 0.2 μg / mL, glucose: 8 mg / mL, bromocresol purple: 37.5 μg / mL). ) The mixture was mixed with 1150 μL, 50 μL each was dispensed into 48 wells / dose of microplate, and statically cultured at 37 ° C. for 3 days. Wells containing bacteria that have acquired growth potential due to mutations in the amino acid (histidine) synthase gene change color from purple to yellow due to pH changes, so the number of bacteria growth wells that turned yellow out of 48 wells per dose was counted. , Evaluated in comparison with the negative control group. Those with negative mutagenicity are shown as (-), and those with positive mutagenicity are shown as (+).
(result)
Compound I-24: (-)

Test Example 13 (hERG test)
For the purpose of assessing the risk of ECG QT interval prolongation of the compound according to the present invention, CHO cells expressing a human ether-a-go-go related gene (hERG) channel play an important role in the ventricular repolarization process. The effect of the compound according to the present invention on delayed rectification K ⁺ current (I _Kr ) was investigated.
Using the fully automatic patch clamp system (QPatch; Sophion Bioscience A / S), the cells are held at a membrane potential of -80 mV by the whole cell patch clamp method, a leak potential of -50 mV is applied, and then a depolarization stimulus of +20 mV is applied. The I _Kr induced when a repolarization stimulus of -50 mV was applied for 2 seconds was recorded. After the generated current stabilizes, extracellular fluid in which the compound according to the present invention is dissolved at the desired concentration (NaCl: 145 mmol / L, KCl: 4 mmol / L, CaCl ₂ : 2 mmol / L, MgCl ₂ : 1 mmol / L, glucose: 10 mmol / L, HEPES (4- (2-hydroxythethyl) -1-piperazinethethelphonic acid, 4- (2-hydroxyethyl) -1-piperazine ethanesulfonic acid): 10 mmol / L, pH = 7.4) is applied to the cells for 10 minutes under room temperature conditions. From the obtained I _Kr , the absolute value of the maximum tail current was measured based on the current value at the holding membrane potential using analysis software (Falster Patch; Sophion Bioscience A / S). Furthermore, the inhibition rate for the maximum tail current before the application of the compound according to the present invention was calculated, and the effect of the compound according to the present invention on I _Kr was evaluated.
(Results) The inhibition rate at a compound concentration of 10 μmol / L is shown.
Compound I-253: 6.9%

Examples of Pharmaceuticals The compounds according to the present invention can be prepared by any conventional route, in particular, by an intestinal route, for example, orally, for example, in the form of tablets or capsules, or parenterally, for example, in the form of an injectable solution or a suspension. It can be administered topically, for example, in the form of a lotion, gel, ointment or cream, or in the form of a nasal or suppository as a pharmaceutical composition. Pharmaceutical compositions comprising a compound of the invention in free or pharmaceutically acceptable salt form, together with at least one pharmaceutically acceptable carrier or diluent, are mixed, in the conventional manner. It can be manufactured by granulation or coating methods. For example, the oral composition can be a tablet, a granule, or a capsule containing an excipient, a disintegrant, a binder, a lubricant, etc., an active ingredient, and the like. Further, the composition for injection may be a solution or a suspension, may be sterilized, or may contain a preservative, a stabilizer, a buffering agent and the like.

Since the pharmaceutical composition of the present invention has an MGAT2 inhibitory effect, for example, obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, hyperfatty acidemia, diabetes, arteriosclerosis, etc. It is useful as a medicine for diseases involving MGAT2.

Claims (8)

formula:

(During the ceremony,
X is C (= O);
R ¹ Is hydrogen;
R ^2a And R ^2b Together with adjacent carbon atoms form ring B,
Ring B is the formula:

(In the formula, R ⁶ Are independently non-aromatic carbocyclic groups that may be substituted with halogen, haloalkyl, haloalkyloxy, halogen or haloalkyl, or non-aromatic heterocyclic groups that may be substituted with halogen or haloalkyl. ,
R ^14a And R ^14b Are independently hydrogen or halogen,
n is an integer of 1 to 3);
R ^3a Is hydrogen,
R ^3b Is hydrogen;
R ^4a Is carboxy or formula:

And;
L ³ Is a single bond or alkylene,
R ⁷ Is a non-aromatic heterocyclic group optionally substituted with hydrogen, halogen, alkylsulfonyl, oxo, a non-aromatic carbocyclic sulfonyl optionally substituted with alkyl, or the formula: —S (= O) ( = NH) -R ^S1 And
R ^4b Is an alkyl substituted with a substituent group α, an aromatic carbocyclic group optionally substituted with a substituent group β, or an aromatic heterocyclic group optionally substituted with a substituent group β. Is the basis and
R ^S1 Is alkyl,
Substituents α are halogen, haloalkyloxy, and non-aromatic carbocyclic groups.
Substituent group β is a compound represented by halogen, cyano, alkyl, haloalkyl, and alkyloxy) or a pharmaceutically acceptable salt thereof.
Ring B is the formula:

(In the formula, R ⁶ Are independently halogen, haloalkyl, or haloalkyloxy, respectively.
R ^14a And R ^14b Are each independently hydrogen,
n is an integer of 1 to 2);
R ^4a Is the formula:

And
L ³ Is alkylene,
R ⁷ Is an alkylsulfonyl
R ^4b Is an alkyl substituted with a substituent group α, an aromatic carbocyclic group optionally substituted with a substituent group β, or an aromatic heterocyclic group optionally substituted with a substituent group β. Is the basis and
Substituent group α is haloalkyloxy,
The pharmaceutical composition according to claim 1, wherein the substituent group β is a halogen and an alkyl.
R ^4b The aromatic carbocyclic group which may be substituted with the substituent group β in the above is a phenyl group which may be substituted with the substituent group β.
R ^4b The aromatic heterocyclic group which may be substituted with the substituent group β in the above is a 5- or 6-membered monocyclic aromatic heterocyclic group which may be substituted with the substituent group β. Item 3. The pharmaceutical composition according to Item 1 or 2.
The pharmaceutical composition according to claim 1, which is selected from the group consisting of the following compounds.

A pharmaceutical composition containing a compound represented by any of the following formulas or a pharmaceutically acceptable salt thereof.

The pharmaceutical composition according to any one of claims 1 to 5 , which is an MGAT2 inhibitor. The pharmaceutical composition according to any one of claims 1 to 6 , which is used for treating or preventing a disease associated with MGAT2. The pharmaceutical composition according to claim 7 , which is used for the treatment or prevention of obesity, metabolic syndrome, hyperlipidemia, hypertriglyceridemia, hyperVLDLemia, hyperfatty acidemia, diabetes or arteriosclerosis.

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