JP2019059697A - Substituted polycyclic pyridazine derivatives and prodrugs thereof - Google Patents

Abstract

To provide substituted polycyclic pyridazine derivatives that exhibit cap-dependent endonuclease inhibitory activity and have anti-influenza action, prodrugs thereof, and pharmaceutical compositions containing the polycyclic pyridazine derivatives.SOLUTION: A compound is represented by the formula (I) in the figure. (P is H or a group forming a prodrug; one of Band Bis NR, and the other is CRR; and Rand Rare H, halogen, hydroxy, carboxy, cyano, formyl, substituted/unsubstituted alkyl, or the like)SELECTED DRAWING: None

Description

  The present invention relates to substituted polycyclic pyridone derivatives exhibiting cap-dependent endonuclease inhibitory activity, their prodrugs, and pharmaceutical compositions containing them.

  Influenza is an acute respiratory infection resulting from an influenza virus infection. In Japan, there are reports of influenza-like patients from millions of people each winter, and influenza is associated with high morbidity and mortality. It is a particularly important disease in high-risk groups such as infants and the elderly, and the merger rate of pneumonia is high in the elderly, and the majority of deaths from influenza are accounted for by the elderly.

As anti-influenza drugs, amantadine (Amantadine; trade name: Symmetrel) and rimantadine (Rimantadine; trade name: Flumadine), which inhibit the nucleation process of virus, suppress budding and release of virus from cells Neuraminidase inhibitors oseltamivir (Oseltamivir; trade name: Tamiflu), zanamivir (Zanamivir; trade name: Relenza), peramivir (Peramivir; trade name: Rapiacta) and raninamivir (Laninamivir; merchandise Name: Inavir (Favipiravir; product name: Aviga), which inhibits RNA polymerase (Avigan)) are known.
However, the development of a novel mechanism of anti-influenza drugs is required because there are concerns about the emergence of resistant strains, side effects, and the global pandemic of highly pathogenic and lethal new influenza viruses. .

  The cap-dependent endonuclease, which is an influenza virus-derived enzyme, is considered to be suitable for anti-influenza drug targets because it is a virus-specific enzyme activity that is essential for virus growth and that the host does not have. . The cap-dependent endonuclease of influenza virus is an endonuclease activity that uses a host mRNA precursor as a substrate and generates a fragment of 9 to 13 bases (not including the bases of the cap structure) containing the cap structure. This fragment functions as a primer for viral RNA polymerase and is used to synthesize mRNA encoding viral proteins. That is, substances that inhibit cap-dependent endonuclease are considered to inhibit viral growth as a result of inhibiting viral protein synthesis by inhibiting viral mRNA synthesis.

  As compounds that inhibit cap-dependent endonucleases, flutimide (patent document 1 and non-patent documents 1 and 2), 4-substituted 2,4-dioxobutanoic acid (patent document 2 and non-patent documents 3 and 4) and In recent years, the compounds and the like described in Patent Documents 3 to 16 have been reported, but have not yet been clinically used as anti-influenza drugs. Patent Document 12 describes a compound having a similar structure to the compound of the present invention, but does not describe the present compound. In addition, Patent Document 17 describes a compound having a similar structure to the compound of the present invention as a compound having HIV integrase inhibitory activity, but does not describe a cap-dependent endonuclease. Patent documents 18 to 21 disclose compounds having a similar structure to the compound of the present invention having cap-dependent endonuclease inhibitory activity and a prodrug thereof filed by the applicant, but the compounds of the present invention Not listed.

German Offenlegungsschrift 2 280 435 U.S. Patent Publication No. 5475109 US Patent Application Publication No. 20130090300 Specification International Publication 2013/057251 brochure International Publication No. 2013/174930 brochure International Publication No. 2014/023691 brochure International Publication No. 2014/043252 brochure International Publication No. 2014/074926 brochure WO 2014/108406 pamphlet International Publication No. 2014/108407 brochure WO 2014/108408 pamphlet WO 2015/038655 pamphlet WO 2015/038660 pamphlet International Publication No. 2016/005330 brochure International Publication No. 2016/005331 brochure International Publication No. 2017/046362 pamphlet WO 2005/016927 pamphlet WO 2010/147068 pamphlet WO 2012/039414 pamphlet International Publication No. 2016/175224 brochure Unexamined-Japanese-Patent No. 2017-137291 specification

Tetrahedron Lett 1995, 36 (12), 2005 Tetrahedron Lett 1995, 36 (12), 2009 Antimicrobial Agents And Chemotherapy, Dec. 1994, p. 2827-2837 Antimicrobial Agents And Chemotherapy, May 1996, p. 1304-1307

  An object of the present invention is to provide a compound having an antiviral activity, in particular, the growth inhibitory activity of influenza virus. Another object of the present invention is to provide a compound which is efficiently absorbed into the body after administration and shows a high pharmacological effect by pro-drugizing the compound used for administration to the living body (for example, oral administration) .

（式中、
Ｐは水素またはプロドラッグを形成する基であり；
Ｂ^１およびＢ^２は、いずれか一方がＮＲ^２、ならびに他方がＣＲ^３ａＲ^３ｂであり；
Ｒ^１は、水素、ハロゲン、ヒドロキシ、カルボキシ、シアノ、ホルミル、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよいアルキルオキシ、置換基群Ｃで置換されていてもよいアルケニルオキシ、置換基群Ｃで置換されていてもよいアルキルカルボニル、置換基群Ｃで置換されていてもよいアルキルオキシカルボニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、置換基群Ｃで置換されていてもよい炭素環オキシ、置換基群Ｃで置換されていてもよい炭素環オキシカルボニル、置換基群Ｃで置換されていてもよい複素環アルキル、置換基群Ｃで置換されていてもよい複素環オキシ、置換基群Ｃで置換されていてもよい複素環オキシカルボニル、
−Ｚ−Ｎ（Ｒ^Ａ１）（Ｒ^Ａ２）、
−Ｚ−Ｎ（Ｒ^Ａ３）−ＳＯ_２−（Ｒ^Ａ４）、
−Ｚ−Ｃ（＝Ｏ）−Ｎ（Ｒ^Ａ５）−ＳＯ_２−（Ｒ^Ａ６）、
−Ｚ−Ｎ（Ｒ^Ａ７）−Ｃ（＝Ｏ）−Ｒ^Ａ８、
−Ｚ−Ｓ−Ｒ^Ａ９、
−Ｚ−ＳＯ_２−Ｒ^Ａ１０、
−Ｚ−Ｓ（＝Ｏ）−Ｒ^Ａ１１、
−Ｚ−Ｎ（Ｒ^Ａ１２）−Ｃ（＝Ｏ）−Ｏ−Ｒ^Ａ１３、
−Ｚ−Ｎ（Ｒ^Ａ１４）−Ｃ（＝Ｏ）−Ｎ（Ｒ^Ａ１５）（Ｒ^Ａ１６）、
−Ｚ−Ｃ（＝Ｏ）−Ｎ（Ｒ^Ａ１７）−Ｃ（＝Ｏ）−Ｎ（Ｒ^Ａ１８）（Ｒ^Ａ１９）、
−Ｚ−Ｎ(Ｒ^Ａ２０）−Ｃ（＝Ｏ）−Ｃ（＝Ｏ）−Ｒ^Ａ２１、
−Ｚ−Ｂ（−ＯＲ^Ａ２２）（−ＯＲ^Ａ２３）または
−Ｚ−ＳＯ_２−Ｎ（Ｒ^Ａ２４）（Ｒ^Ａ２５）、
（ここで、Ｒ^Ａ１、Ｒ^Ａ２、Ｒ^Ａ３、Ｒ^Ａ５、Ｒ^Ａ７、Ｒ^Ａ８、Ｒ^Ａ９、Ｒ^Ａ１２、Ｒ^Ａ１３、Ｒ^Ａ１４、Ｒ^Ａ１５、Ｒ^Ａ１６、Ｒ^Ａ１７、Ｒ^Ａ１８、Ｒ^Ａ１９、Ｒ^Ａ２０、Ｒ^Ａ２１、Ｒ^Ａ２４、およびＲ^Ａ２５は、それぞれ独立して、水素、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、および置換基群Ｃで置換されていてもよい複素環アルキルからなる置換基群から選ばれ、
Ｒ^Ａ４、Ｒ^Ａ６、Ｒ^Ａ１０、およびＲ^Ａ１１はそれぞれ独立して、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、および置換基群Ｃで置換されていてもよい複素環アルキルからなる置換基群から選ばれ、
Ｒ^Ａ１およびＲ^Ａ２、Ｒ^Ａ１５およびＲ^Ａ１６、ならびにＲ^Ａ１８およびＲ^Ａ１９は、隣接する原子と一緒になって複素環を形成していてもよく、
Ｒ^Ａ２２、およびＲ^Ａ２３はそれぞれ独立して、水素原子、置換基群Ｃで置換されていてもよいアルキル、またはＲ^Ａ２２、およびＲ^Ａ２３が一緒になっては、隣接する原子と一緒になって複素環を形成していてもよく、ならびに
Ｚは、単結合または直鎖もしくは分枝状のアルキレンである）であり；

Ｒ^２、Ｒ^３ａおよびＲ^３ｂは、それぞれ独立して水素、カルボキシ、シアノ、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよいアルキルカルボニル、置換基群Ｃで置換されていてもよいアルキルオキシカルボニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、置換基群Ｃで置換されていてもよい炭素環オキシアルキル、置換基群Ｃで置換されていてもよい炭素環カルボニル、置換基群Ｃで置換されていてもよい炭素環オキシカルボニル、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい複素環アルキル、置換基群Ｃで置換されていてもよい複素環オキシアルキル、置換基群Ｃで置換されていてもよい複素環カルボニル、置換基群Ｃで置換されていてもよい複素環オキシカルボニル、
−Ｙ−Ｓ−Ｒ^B１、
−Ｚ−Ｓ（＝Ｏ）−Ｒ^B２、
−Ｚ−ＳＯ_２−Ｒ^B３、
−Ｃ（＝Ｏ）−Ｃ（＝Ｏ）−Ｒ^B４、
−Ｃ（＝Ｏ）−Ｎ（Ｒ^B５）（Ｒ^B６）、
−Ｚ−Ｃ（Ｒ^B７）（Ｒ^B８）（Ｒ^B９）、
−Ｚ−ＣＨ_２−Ｒ^B１０、
−Ｚ−Ｎ（Ｒ^B１１）−Ｃ（＝Ｏ）−Ｏ−Ｒ^B１２、もしくは
−Ｚ−Ｎ（Ｒ^B１３）−Ｃ（＝Ｏ）−Ｒ^B１４
（ここで、Ｒ^B１、Ｒ^B４、Ｒ^B５、Ｒ^B６、Ｒ^B９、Ｒ^B１１、Ｒ^B１２、Ｒ^B１３、およびＲ^B１４はそれぞれ独立して、水素、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、および置換基群Ｃで置換されていてもよい複素環アルキルからなる置換基群から選ばれ、
Ｒ^B２、およびＲ^B３はそれぞれ独立して、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、および置換基群Ｃで置換されていてもよい複素環アルキルからなる置換基群から選ばれ、
Ｒ^B７、Ｒ^B８、およびＲ^B１０はそれぞれ独立して、置換基群Ｃで置換されていてもよい炭素環式基、または置換基群Ｃで置換されていてもよい複素環式基であり、
Ｒ^B５およびＲ^B６は、隣接する原子と一緒になって複素環を形成していてもよく、
Ｙは、直鎖もしくは分枝状のアルキレンであり、ならびに
Ｚは、単結合または直鎖もしくは分枝状のアルキレンである）であり
；

Ｒ^４は、水素、ハロゲン、ヒドロキシ、カルボキシ、シアノ、ホルミル、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよいアルキルオキシ、置換基群Ｃで置換されていてもよいアルケニルオキシ、置換基群Ｃで置換されていてもよいアルキルカルボニル、置換基群Ｃで置換されていてもよいアルキルオキシカルボニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、置換基群Ｃで置換されていてもよい炭素環オキシアルキル、置換基群Ｃで置換されていてもよい炭素環カルボニル、置換基群Ｃで置換されていてもよい炭素環オキシ、置換基群Ｃで置換されていてもよい炭素環オキシカルボニル、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい複素環アルキル、置換基群Ｃで置換されていてもよい複素環オキシアルキル、置換基群Ｃで置換されていてもよい複素環カルボニル、置換基群Ｃで置換されていてもよい複素環オキシ、置換基群Ｃで置換されていてもよい複素環オキシカルボニル、
−Ｚ−Ｎ（Ｒ^Ｃ１）−ＳＯ_２−Ｒ^Ｃ２、
−Ｚ−Ｎ（Ｒ^Ｃ３）−Ｃ（＝Ｏ）−Ｒ^Ｃ４、
−Ｚ−Ｎ（Ｒ^Ｃ５）−Ｃ（＝Ｏ）−Ｏ−Ｒ^Ｃ６、
−Ｚ−Ｃ（＝Ｏ）−Ｎ（Ｒ^Ｃ７）（Ｒ^Ｃ８）、
−Ｚ−Ｎ（Ｒ^Ｃ９）（Ｒ^Ｃ１０）、
−Ｚ−ＳＯ_２−Ｒ^Ｃ１１、または
−Ｚ−Ｎ（Ｒ^Ｃ１２）−Ｏ−Ｃ（＝Ｏ）−Ｒ^Ｃ１３
（ここで、Ｒ^Ｃ１、Ｒ^Ｃ３、Ｒ^Ｃ４、Ｒ^Ｃ５、Ｒ^Ｃ６、Ｒ^Ｃ７、Ｒ^Ｃ８、Ｒ^Ｃ９、Ｒ^Ｃ１０、Ｒ^Ｃ１２および、Ｒ^Ｃ１３は、それぞれ独立して、水素、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、および置換基群Ｃで置換されていてもよい複素環アルキルからなる置換基群から選ばれ、
Ｒ^Ｃ２、およびＲ^Ｃ１１はそれぞれ独立して、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルケニル、置換基群Ｃで置換されていてもよいアルキニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、および置換基群Ｃで置換されていてもよい複素環アルキルからなる置換基群から選ばれ、
Ｒ^Ｃ７およびＲ^Ｃ８、ならびにＲ^Ｃ９およびＲ^Ｃ１０は、隣接する原子と一緒になって複素環を形成していてもよく、ならびに
Ｚは、単結合または直鎖もしくは分枝状のアルキレンである）であり；

１）Ｂ^１がＮＲ^２、およびＢ^２がＣＲ^３ａＲ^３ｂの場合、Ｒ^３ｂおよびＲ^４は隣接する原子と一緒になって置換基群Ｄで置換されていてもよい複素環を形成していてもよく、さらに該複素環は、架橋を形成してもよく、もしくは
Ｒ^３ａおよびＲ^３ｂは、隣接する原子と一緒になって置換基群Ｄで置換されていてもよい炭素環または複素環を形成していてもよく、または
２）Ｂ^１がＣＲ^３ａＲ^３ｂ、およびＢ^２がＮＲ^２の場合、Ｒ^２およびＲ^４は隣接する原子と一緒になって置換基群Ｄで置換されていてもよい複素環を形成していてもよく、さらに該複素環は、架橋を形成してもよい；

置換基群Ｃ：ハロゲン、シアノ、ヒドロキシ、カルボキシ、ホルミル、アミノ、オキソ、ニトロ、アルキル、アルケニル、アルキニル、ハロアルキル、アルキルオキシ、アルキニルオキシ、アルキルチオ、ヒドロキシアルキル、炭素環式基、複素環式基、オキソ置換複素環式基、炭素環アルキルオキシ、炭素環オキシアルキル、炭素環アルキルオキシアルキル、複素環アルキルオキシ、複素環オキシアルキル、複素環アルキルオキシアルキル、ハロアルキルオキシ、アルキルオキシアルキル、アルキルオキシアルキルオキシ、アルキルカルボニル、アルキルカルボニルオキシ、アルキルオキシカルボニル、アルキルアミノ、アルキルカルボニルアミノ、ハロアルキルカルボニルアミノ、アルキルアミノカルボニル、アルキルスルホニル、アルキルスルフィニル、およびアルキルスルホニルアミノ；

置換基群Ｄ：ハロゲン、シアノ、ヒドロキシ、カルボキシ、ホルミル、アミノ、オキソ、ニトロ、アルキル、ハロアルキル、アルキルオキシ、炭素環アルキルオキシ、複素環アルキルオキシ、ハロアルキルオキシ、アルキルオキシアルキル、アルキルオキシアルキルオキシ、アルキルカルボニル、アルキルオキシカルボニル、アルキルアミノ、アルキルカルボニルアミノ、アルキルアミノカルボニル、アルキルスルホニル、アルキルスルホニルアミノ、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、および置換基群Ｃで置換されていてもよい複素環アルキル）
で示される化合物、またはその製薬上許容される塩。

（２）Ｒ^１が、水素、カルボキシ、または−Ｚ−Ｎ（Ｒ^Ａ１）（Ｒ^Ａ２）である、上記（１）記載の化合物、またはその製薬上許容される塩。
（３）Ｒ^４が、水素、または置換基群Ｃで置換されていてもよいアルキルである、上記（１）または（２）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。
（４）Ｒ^２、Ｒ^３ａおよびＲ^３ｂが、それぞれ独立して水素、カルボキシ、シアノ、置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよいアルキルカルボニル、置換基群Ｃで置換されていてもよいアルキルオキシカルボニル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい複素環アルキル、
−Ｙ−Ｓ−Ｒ^B１、
−Ｚ−Ｓ（＝Ｏ）−Ｒ^B２、
−Ｚ−ＳＯ_２−Ｒ^B３、
−Ｃ（＝Ｏ）−Ｃ（＝Ｏ）−Ｒ^B４、
−Ｃ（＝Ｏ）−Ｎ（Ｒ^B５）（Ｒ^B６）、
−Ｚ−Ｃ（Ｒ^B７）（Ｒ^B８）（Ｒ^B９）
−Ｚ−Ｎ（Ｒ^B１１）−Ｃ（＝Ｏ）−Ｏ−Ｒ^B１２、または
−Ｚ−Ｎ（Ｒ^B１３）−Ｃ（＝Ｏ）−Ｒ^B１４
である、上記（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。
（５）Ｂ^１がＮＲ^２であり、およびＢ^２がＣＲ^３ａＲ^３ｂであり、
Ｒ^２が置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい炭素環オキシアルキル、置換基群Ｃで置換されていてもよい複素環式基、換基群Ｃで置換されていてもよい炭素環アルキル、換基群Ｃで置換されていてもよい複素環アルキル、または
−Ｚ−Ｃ（Ｒ^B７）（Ｒ^B８）（Ｒ^B９）であり、
Ｒ^３ａが水素であり、ならびに
Ｒ^３ｂが水素、または置換基群Ｃで置換されていてもよいアルキル
である、上記（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。
（６）Ｂ^１がＮＲ^２であり、およびＢ^２がＣＲ^３ａＲ^３ｂであり、
Ｒ^２が置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい炭素環オキシアルキル、置換基群Ｃで置換されていてもよい複素環式基、換基群Ｃで置換されていてもよい炭素環アルキル、換基群Ｃで置換されていてもよい複素環アルキル、または
−Ｚ−Ｃ（Ｒ^B７）（Ｒ^B８）（Ｒ^B９）であり、
Ｒ^３ａが水素であり、ならびに
Ｒ^３ｂおよびＲ^４が隣接する原子と一緒になって置換基群Ｄで置換されていてもよい複素環を形成し、さらに該複素環が架橋を形成してもよい、
上記（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。
（７）１Ｒ^２が、以下に示される基：

（式中、Ｒ^Ｅ6は、置換基群Ｃから選ばれ、ｍは０または１以上の整数であり、
但し、ｍ個のＲ^Ｅ6は、置換基群Ｃから選ばれる同一または異なっていてもよい基である）である、上記（５）または（６）記載の化合物、またはその製薬上許容される塩。
（８）Ｂ^１がＣＲ^３ａＲ^３ｂであり、およびＢ^２がＮＲ^２であり、
Ｒ^２が水素、または置換基群Ｃで置換されていてもよいアルキルであり、
Ｒ^３ａが水素であり、ならびに
Ｒ^３ｂが置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい炭素環オキシアルキル、置換基群Ｃで置換されていてもよい複素環式基、換基群Ｃで置換されていてもよい炭素環アルキル、換基群Ｃで置換されていてもよい複素環アルキル、または
−Ｚ−Ｃ（Ｒ^B７）（Ｒ^B８）（Ｒ^B９）
である、上記（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。
（９）Ｂ^１がＣＲ^３ａＲ^３ｂであり、およびＢ^２がＮＲ^２であり、
Ｒ^３ａが水素であり、
Ｒ^３ｂが置換基群Ｃで置換されていてもよいアルキル、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい炭素環オキシアルキル、置換基群Ｃで置換されていてもよい複素環式基、換基群Ｃで置換されていてもよい炭素環アルキル、換基群Ｃで置換されていてもよい複素環アルキル、または
−Ｚ−Ｃ（Ｒ^B７）（Ｒ^B８）（Ｒ^B９）であり、ならびに
Ｒ^２およびＲ^４は隣接する原子と一緒になって置換基群Ｄで置換されていてもよい複素環を形成し、さらに該複素環が架橋を形成してもよい、
上記（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。
（１０）２Ｒ^３ｂが、以下に示される基：

（式中、Ｒ^Ｅ6は、置換基群Ｃから選ばれ、ｍは０または１以上の整数であり、
但し、ｍ個のＲ^Ｅ6は、置換基群Ｃから選ばれる同一または異なっていてもよい基である）である、上記（８）または（９）記載の化合物、またはその製薬上許容される塩。
（１１）３置換基群Ｄが、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、置換基群Ｃで置換されていてもよい炭素環式基、置換基群Ｃで置換されていてもよい複素環式基、置換基群Ｃで置換されていてもよい炭素環アルキル、または置換基群Ｃで置換されていてもよい複素環アルキルである、上記（１）、（６）、または（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。
（１２）Ｐが水素である、上記（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。
（１３）Ｐがプロドラッグを形成する基であり、該プロドラッグを形成する基が以下の式ａ）〜ａｃ）から選ばれる基；
ａ）−Ｃ（＝Ｏ）−Ｐ^Ｒ０、
ｂ）−Ｃ（＝Ｏ）−Ｐ^Ｒ１、
ｃ）−Ｃ（＝Ｏ）−Ｌ−Ｐ^Ｒ１、
ｄ）−Ｃ（＝Ｏ）−Ｌ−Ｏ−Ｐ^Ｒ１、
ｅ）−Ｃ（＝Ｏ）−Ｌ−Ｏ−Ｌ−Ｏ−Ｐ^Ｒ１、
ｆ）−Ｃ（＝Ｏ）−Ｌ−Ｏ−Ｃ（＝Ｏ）−Ｐ^Ｒ１、
ｇ）−Ｃ（＝Ｏ）−Ｏ−Ｐ^Ｒ２、
ｈ）−Ｃ（＝Ｏ）−Ｎ（−Ｋ）（Ｐ^Ｒ２）、
ｉ）−Ｃ（＝Ｏ）−Ｏ−Ｌ−Ｏ−Ｐ^Ｒ２、
ｊ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｐ^Ｒ４、
ｋ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｌ−Ｏ−Ｐ^Ｒ４、
ｌ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｐ^Ｒ４、
ｍ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｏ−Ｐ^Ｒ４、
ｎ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｎ（−Ｋ）−Ｐ^Ｒ４、
ｏ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｏ−Ｌ−Ｏ−Ｐ^Ｒ４、
ｐ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｏ−Ｌ−Ｎ（Ｐ^Ｒ４）_２、
ｑ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｎ（−Ｋ）−Ｌ−Ｏ−Ｐ^Ｒ４、
ｒ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｎ（−Ｋ）−Ｌ−Ｎ（Ｐ^Ｒ４）_２、
ｓ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｏ−Ｌ−Ｏ−Ｌ−Ｏ−Ｐ^Ｒ４、
ｔ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｃ（＝Ｏ）−Ｏ−Ｌ−Ｎ（−Ｋ）−Ｃ（＝Ｏ）−Ｐ^Ｒ４、
ｕ）−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｐ（＝Ｏ）（−Ｐ^Ｒ５）_２、
ｖ）−Ｃ（Ｐ^Ｒ３）_２−Ｐ^Ｒ６、
ｗ）−Ｃ（＝Ｎ^＋（Ｐ^Ｒ７）_２）（−Ｎ（Ｐ^Ｒ７）_２）、
ｘ）−Ｃ（Ｐ^Ｒ３）_２−Ｃ（Ｐ^Ｒ３）_２−Ｃ（＝Ｏ）−Ｏ−Ｐ^Ｒ２、
ｙ）−Ｃ（Ｐ^Ｒ３）_２−Ｎ（−Ｋ）−Ｃ（＝Ｏ）−Ｏ−Ｐ^Ｒ２、
ｚ）−Ｐ（＝Ｏ）（−Ｐ^Ｒ８）（−Ｐ^Ｒ９）、
ａａ）−Ｓ（＝Ｏ）_２−Ｐ^Ｒ１０、
ａｂ）−Ｐ^Ｒ１１、および
ａｃ）−Ｃ（Ｐ^Ｒ３）_２−Ｃ（Ｐ^Ｒ３）_２−Ｏ−Ｐ^Ｒ２、
（式中、Ｌは、直鎖もしくは分枝状のアルキレン、または直鎖もしくは分枝状のアルケニレンであり、
Ｋは、水素、または置換基群Ａで置換されていてもよいアルキルであり、
Ｐ^Ｒ０は、置換基群Ａで置換されていてもよいアルキル、または置換基群Ａで置換されていてもよいアルケニルであり、
Ｐ^Ｒ１は、置換基群Ａで置換されていてもよい炭素環式基、置換基群Ａで置換されていてもよい複素環式基、置換基群Ａで置換されていてもよいアルキルアミノ、または置換基群Ａで置換されていてもよいアルキルスルファニルであり、
Ｐ^Ｒ２は、置換基群Ａで置換されていてもよいアルキル、置換基群Ａで置換されていてもよい炭素環式基、置換基群Ａで置換されていてもよい複素環式基、置換基群Ａで置換されていてもよい炭素環アルキル、置換基群Ａで置換されていてもよい複素環アルキル、またはトリアルキルシリルであり、
Ｐ^Ｒ３は、それぞれ独立して、水素、アルキルであり、
Ｐ^Ｒ４は、それぞれ独立して、置換基群Ａで置換されていてもよいアルキル、置換基群Ａで置換されていてもよい炭素環式基、置換基群Ａで置換されていてもよい複素環式基、置換基群Ａで置換されていてもよいアルキルアミノ、置換基群Ａで置換されていてもよい炭素環アルキル、置換基群Ａで置換されていてもよい複素環アルキル、またはトリアルキルシリルであり、
Ｐ^Ｒ５は、それぞれ独立して、ヒドロキシまたはＯＢｎであり、
Ｐ^Ｒ６は、置換基群Ａで置換されていてもよい炭素環式基、または置換基群Ａで置換されていてもよい複素環式基であり、
Ｐ^Ｒ７は、それぞれ独立して、置換基群Ａで置換されていてもよいアルキルであり、
Ｐ^Ｒ８は、置換基群Ａで置換されていてもよいアルキルオキシであり、
Ｐ^Ｒ９は、置換基群Ａで置換されていてもよいアルキルオキシ、置換基群Ａで置換されていてもよいアルキルアミノ、置換基群Ａで置換されていてもよい炭素環オキシ、置換基群Ａで置換されていてもよい複素環オキシ、置換基群Ａで置換されていてもよい炭素環アミノ、または置換基群Ａで置換されていてもよい複素環アミノであり、
Ｐ^Ｒ８およびＰ^Ｒ９は、隣接するリン原子と一緒になって、置換基群Ａで置換されていてもよい複素環を形成してもよく、
Ｐ^Ｒ１０は、置換基群Ａで置換されていてもよいアルキル、置換基群Ａで置換されていてもよい炭素環式基、置換基群Ａで置換されていてもよい複素環式基、置換基群Ａで置換されていてもよい炭素環アルキル、または置換基群Ａで置換されていてもよい複素環アルキルであり、ならびに、
Ｐ^Ｒ１１は、置換基群Ａで置換されていてもよいアルキル、置換基群Ａで置換されていてもよいアルケニル、置換基群Ａで置換されていてもよい炭素環式基、または置換基群Ａで置換されていてもよい複素環式基である。
置換基群Ａ；オキソ、アルキル、ヒドロキシアルキル、アミノ、アルキルアミノ、炭素環式基、複素環式基、炭素環アルキル、アルキルカルボニル、ハロゲン、ヒドロキシ、カルボキシ、アルキルカルボニルアミノ、アルキルカルボニルアミノアルキル、アルキルカルボニルオキシ、アルキルオキシカルボニル、アルキルオキシカルボニルアルキル、アルキルオキシカルボニルオキシ、アルキルアミノカルボニルオキシ、アルキルアミノアルキル、アルキルオキシ、シアノ、ニトロ、アジド、アルキルスルホニル、トリアルキルシリル、およびホスホ）である上記（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。
（１４）上記（１）〜（１３）のいずれかに記載の化合物、その製薬上許容される塩、またはそれらの溶媒和物を含有する抗ウイルス剤。
（１５）抗インフルエンザ作用を有する、上記（１４）記載の抗ウイルス剤。
（１６）インフルエンザ感染症の治療および／または予防のための、上記（１）〜（１３）のいずれかに記載の化合物。
（１７）上記（１）〜（１３）のいずれかに記載の化合物、その製薬上許容される塩、またはそれらの溶媒和物を投与することを特徴とする、インフルエンザ感染症の治療および／または予防方法。
（１８）キャップ依存的エンドヌクレアーゼ阻害作用を有する、上記（１４）記載の抗ウイルス剤。
（１９）上記（１）〜（１３）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投与することを特徴とする、キャップ依存的エンドヌクレアーゼを有するウイルスにより引き起こされる疾患の治療または予防方法。
（２０）キャップ依存的エンドヌクレアーゼを有するウイルスにより引き起こされる疾患の治療または予防剤を製造するための、上記（１）〜（１３）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の使用。
（２１）上記（１）〜（１３）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、経口投与のための抗ウイルス剤。
（２２）錠剤、散剤、顆粒剤、カプセル剤、丸剤、フィルム剤、懸濁剤、乳剤、エリキシル剤、シロップ剤、リモナーデ剤、酒精剤、芳香水剤、エキス剤、煎剤またはチンキ剤である、（２１）記載の抗ウイルス剤。
（２３）糖衣錠、フィルムコーティング錠、腸溶性コーティング錠、徐放錠、トローチ錠、舌下錠、バッカル錠、チュアブル錠、口腔内崩壊錠、ドライシロップ、ソフトカプセル剤、マイクロカプセル剤または徐放性カプセル剤である、（２１）記載の抗ウイルス剤。
（２４）上記（１）〜（１３）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、非経口投与のための抗ウイルス剤。
（２５）経皮、皮下、静脈内、動脈内、筋肉内、腹腔内、経粘膜、吸入、経鼻、点眼、点耳または膣内投与のための、（２４）記載の抗ウイルス剤。
（２６）注射剤、点滴剤、点眼剤、点鼻剤、点耳剤、エアゾール剤、吸入剤、ローション剤、注入剤、塗布剤、含嗽剤、浣腸剤、軟膏剤、硬膏剤、ゼリー剤、クリーム剤、貼付剤、パップ剤、外用散剤または坐剤である、（２４）または（２５）記載の抗ウイルス剤。
（２７）上記（１）〜（１３）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、小児用または高齢者用の抗ウイルス剤。
（２８）上記（１）〜（１３）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と、ノイラミニダーゼ阻害剤、ＲＮＡ依存性ＲＮＡポリメラーゼ阻害剤、Ｍ２タンパク阻害剤、ＰＢ２ Ｃａｐ結合阻害剤、抗ＨＡ抗体、または免疫作用薬との組み合わせからなる抗ウイルス剤。
（２９）上記（１）〜（１３）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、ノイラミニダーゼ阻害剤、ＲＮＡ依存性ＲＮＡポリメラーゼ阻害剤、Ｍ２タンパク阻害剤、ＰＢ２ Ｃａｐ結合阻害剤、抗ＨＡ抗体、または免疫作用薬との併用療法のための抗ウイルス剤。 The present invention provides the invention shown below.
(1) Formula (I):

(In the formula,
P is hydrogen or a group forming a prodrug;
One of B ¹ and B ² is NR ² , and the other is CR ^3a R ^3b ;
R ¹ is hydrogen, halogen, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, substituted with substituent group C Optionally alkynyl, alkyloxy optionally substituted with substituent group C, alkenyloxy optionally substituted with substituent group C, alkylcarbonyl optionally substituted with substituent group C, substituent group Alkyloxycarbonyl which may be substituted by C, carbocyclic group which may be substituted by substituent group C, carbocyclic alkyl which may be substituted by substituent group C, substituted by substituent group C Optionally substituted carbocycle oxy, optionally substituted carbocycle oxycarbonyl, optionally substituted substituent C, optionally substituted heterocyclic alkyl, optionally substituted substituent C Heterocyclic oxy, heterocyclic oxycarbonyl optionally substituted with substituent group C,
-Z-N (R ^A1 ) (R ^A2 ),
_{^{-Z-N (R A3) -SO}} 2 - (R A4),
^{-Z-C (= O) -N} (R A5) -SO 2 - (R A6),
-Z-N ( ^RA7 ) -C (= O) ^-RA8 ,
-Z-S-R ^A9 ,
-Z-SO _2- R ^A10 ,
-Z-S (= O) ^-RA11 ,
-Z-N (R < ^A12 >)-C (= O) -O-R < ^A13 >,
-Z-N ( ^RA14 ) -C (= O) -N ( ^RA15 ) ( ^RA16 ),
-Z-C (= O) -N ( ^RA17 ) -C (= O) -N ( ^RA18 ) ( ^RA19 ),
-Z-N ( ^RA20 ) -C (= O) -C (= O) ^-RA21 ,
-Z-B (-OR ^A22 ) (-OR ^A23 ) or -Z-SO ₂ -N (R ^A24 ) (R ^A25 ),
(Here, R ^A1 , R ^A2 , R ^A3 , R ^A5 , R ^A7 , R ^A8 , R ^A9 , R ^A12 , R ^A13 , R ^A14 , R ^A15 , R ^A16 , R ^A17 , R ^A18 , R ^A19 , R ^{A19 A20} , R ^A21 , R ^A24 and R ^A25 are each independently hydrogen, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, substituent group C Embedded image optionally substituted alkynyl, substituted carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, substituted by substituent group C It is selected from the substituent group consisting of optionally substituted carbocyclic alkyl, and heterocyclic alkyl optionally substituted by substituent group C,
R ^A4 , R ^A6 , R ^A10 and R ^A11 are each independently an alkyl which may be substituted with substituent group C, an alkenyl which may be substituted with substituent group C, and a substituent group C Alkynyl which may be substituted, carbocyclic group which may be substituted with substituent group C, heterocyclic group which may be substituted with substituent group C, which may be substituted with substituent group C It is selected from the substituent group consisting of carbocyclic alkyl and heterocyclic alkyl optionally substituted by substituent group C,
R ^A1 and R ^A2 , R ^A15 and R ^A16 , and R ^A18 and R ^A19 may ^combine with adjacent atoms to form a heterocyclic ring,
R ^A22 and R ^A23 each independently represent a hydrogen atom, an alkyl which may be substituted with substituent group C, or R ^A22 and R ^A23 together with the adjacent atom And may form a heterocyclic ring, and Z is a single bond or linear or branched alkylene);

R ² , R ^3a and R ^3b are each independently hydrogen, carboxy, cyano, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, substituent group C , An optionally substituted alkynyl, a substituted group C optionally substituted alkylcarbonyl, a substituted group C optionally substituted alkyloxycarbonyl, and a substituted group C optionally substituted carbon Cyclic group, carbocyclic ring alkyl which may be substituted by substituent group C, carbocyclic ring oxyalkyl which may be substituted by substituent group C, carbocyclic ring carbonyl which may be substituted by substituent group C, Carbocyclic oxycarbonyl optionally substituted with substituent group C, heterocyclic group optionally substituted with substituent group C, heterocyclic alkyl optionally substituted with substituent group C, substituent group C And heterocyclic oxyalkyl which may be substituted, heterocyclic carbonyl which may be substituted with substituent group C, heterocyclic oxycarbonyl which may be substituted with substituent group C,
-Y-S-R ^B1 ,
-Z-S (= O) -R B2,
-Z-SO _2- R ^B3 ,
-C (= O) -C (= O) -R B4,
-C (= O) -N (R ^B5 ) (R ^B6 ),
-Z-C ( ^RB7 ) ( ^RB8 ) ( ^RB9 ),
_-Z-CH 2 -R ^B10,
-Z-N ( ^RB11 ) -C (= O) -O- ^RB12 or -Z-N ( ^RB13 ) -C (= O) ^-RB14
(Wherein, R ^B1 , R ^B4 , R ^B5 , R ^B6 , R ^B9 , R ^B11 , R ^B12 , R ^B13 , and R ^B14 may be each independently substituted with hydrogen or substituent group C. Alkyl, alkenyl optionally substituted with substituent group C, alkynyl optionally substituted with substituent group C, carbocyclic group optionally substituted with substituent group C, substituted with substituent group C A substituent group selected from a heterocyclic group which may be substituted, a carbocyclic alkyl which may be substituted with a substituent group C, and a heterocyclic alkyl which may be substituted with a substituent group C,
R ^B2 and R ^B3 are each independently an alkyl which may be substituted with substituent group C, an alkenyl which may be substituted with substituent group C, an alkynyl which may be substituted with substituent group C A carbocyclic group which may be substituted with substituent group C, a heterocyclic group which may be substituted with substituent group C, a carbocyclic alkyl which may be substituted with substituent group C, and a substituent It is selected from the substituent group consisting of the heterocyclic alkyl which may be substituted by the group group C,
R ^B7 , R ^B8 and R ^B10 are each independently a carbocyclic group which may be substituted with substituent group C or a heterocyclic group which may be substituted with substituent group C,
R ^B5 and R ^B6 may form a heterocycle together with adjacent atoms,
Y is linear or branched alkylene, and Z is a single bond or linear or branched alkylene)

R ⁴ is hydrogen, halogen, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, substituted with substituent group C Optionally alkynyl, alkyloxy optionally substituted with substituent group C, alkenyloxy optionally substituted with substituent group C, alkylcarbonyl optionally substituted with substituent group C, substituent group Alkyloxycarbonyl which may be substituted by C, carbocyclic group which may be substituted by substituent group C, carbocyclic alkyl which may be substituted by substituent group C, substituted by substituent group C Optionally substituted carbocyclic oxyalkyl, optionally substituted carbocyclic ring carbonyl, optionally substituted carbocyclic ring oxy, optionally substituted substituent C Carbocyclic ring oxycarbonyl which may be substituted, heterocyclic group which may be substituted with substituent group C, heterocyclic alkyl which may be substituted with substituent group C, even if substituted with substituent group C Good heterocyclic oxyalkyl, heterocyclic carbonyl optionally substituted with substituent group C, heterocyclic oxy optionally substituted with substituent group C, heterocyclic oxy optionally substituted with substituent group C Carbonyl,
_{^{-Z-N (R C1) -SO}} 2 -R C2,
-Z-N (R < ^C3 >)-C (= O) -R < ^C4 >,
-Z-N (R < ^C5 >)-C (= O) -O-R < ^C6 >,
-Z-C (= O) -N (R ^C7 ) (R ^C8 ),
-Z-N (R ^<C9> ) (R ^<C10> ),
_-Z-SO ^{2 -R C11} or ^{-Z-N (R C12),} -O-C (= O) -R C13
(Where, R ^C1 , R ^C3 , R ^C4 , R ^C5 , R ^C6 , R ^C7 , R ^C8 , R ^C9 , R ^C10 , R ^C12 and R ^C13 are each independently hydrogen, substituent group C Alkyl which may be substituted, alkenyl which may be substituted with substituent group C, alkynyl which may be substituted with substituent group C, carbocyclic group which may be substituted with substituent group C A heterocyclic group optionally substituted with substituent group C, a carbocyclic alkyl optionally substituted with substituent group C, and a heterocyclic alkyl optionally substituted with substituent group C Selected from the group
R ^C2 and R ^C11 are each independently alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, and alkynyl optionally substituted with substituent group C A carbocyclic group which may be substituted with substituent group C, a heterocyclic group which may be substituted with substituent group C, a carbocyclic alkyl which may be substituted with substituent group C, and a substituent It is selected from the substituent group consisting of the heterocyclic alkyl which may be substituted by the group group C,
R ^C7 and R ^C8 , and R ^C9 and R ^C10 may be taken together with adjacent atoms to form a heterocycle, and Z is a single bond or a linear or branched alkylene. And

1) When B ¹ is NR ² and B ² is CR ^3a R ^3b , R ^3b and R ⁴ are combined with adjacent atoms to form a heterocyclic ring which may be substituted by Substituent Group D Further, the heterocyclic ring may form a bridge, or R ^3a and R ^3b may be a carbocyclic or heterocyclic ring optionally substituted with substituent group D together with the adjacent atoms Or 2) when B ¹ is CR ^3a R ^3b , and B ² is NR ² , R ² and R ⁴ together with the adjacent atoms are substituted with substituent group D And may form a heterocyclic ring, and the heterocyclic ring may further form a bridge;

Substituent group C: halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkynyloxy, alkylthio, hydroxyalkyl, carbocyclic group, heterocyclic group, Oxo substituted heterocyclic group, carbocyclic alkyloxy, carbocyclic oxyalkyl, carbocyclic alkyloxyalkyl, heterocyclic alkyloxy, heterocyclic oxyalkyl, heterocyclic alkyloxyalkyl, haloalkyloxy, alkyloxyalkyl, alkyloxyalkyloxy , Alkylcarbonyl, alkylcarbonyloxy, alkyloxycarbonyl, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, alkylaminocarbonyl, alkylsulfonyl, al Rusurufiniru, and alkylsulfonylamino;

Substituent group D: Halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, alkyl, haloalkyl, alkyloxy, carbocyclic alkyloxy, heterocyclic alkyloxy, haloalkyloxy, alkyloxyalkyl, alkyloxyalkyloxy, Alkylcarbonyl, alkyloxycarbonyl, alkylamino, alkylcarbonylamino, alkylaminocarbonyl, alkylsulfonyl, alkylsulfonylamino, carbocyclic group which may be substituted by substituent group C, substituted by substituent group C Heterocyclic group, carbocyclic alkyl optionally substituted with substituent group C, and heterocyclic alkyl optionally substituted with substituent group C)
Or a pharmaceutically acceptable salt thereof.

(2) The compound according to the above (1) or a pharmaceutically acceptable salt thereof, wherein R ¹ is hydrogen, carboxy, or -Z-N (R ^A1 ) (R ^A2 ).
(3) The compound according to any one of the above (1) or (2), or a pharmaceutically acceptable salt thereof, wherein R ⁴ is hydrogen or alkyl optionally substituted with substituent group C.
(4) R ² , R ^3a and R ^3b are each independently hydrogen, carboxy, cyano, alkyl optionally substituted with substituent group C, alkylcarbonyl optionally substituted with substituent group C, Alkyloxycarbonyl optionally substituted with substituent group C, carbocyclic group optionally substituted with substituent group C, carbocyclic alkyl optionally substituted with substituent group C, substituent group C A heterocyclic group which may be substituted, a heterocyclic alkyl which may be substituted with substituent group C,
-Y-S-R ^B1 ,
-Z-S (= O) -R B2,
-Z-SO _2- R ^B3 ,
-C (= O) -C (= O) -R B4,
-C (= O) -N (R ^B5 ) (R ^B6 ),
-Z-C ( ^RB7 ) ( ^RB8 ) ( ^RB9 )
-Z-N ( ^RB11 ) -C (= O) -O- ^RB12 or -Z-N ( ^RB13 ) -C (= O) ^-RB14
Or the pharmaceutically acceptable salt thereof according to any one of the above (1) to (3).
(5) B ¹ is NR ² and B ² is CR ^3a R ^3b ,
R ² is alkyl may be substituted with a substituent group C, substituted with a substituent group C which may be carbocyclic group, which may be carbocyclic aryloxy substituted with a substituent group C, substituents A heterocyclic group which may be substituted by group C, a carbocyclic alkyl which may be substituted by a substituent group C, a heterocyclic alkyl which may be substituted by a substituent group C, or -Z-C ( R ^B7 ) (R ^B8 ) (R ^B9 ),
The compound according to any one of the above (1) to (4), wherein R ^3a is hydrogen and R ^3b is hydrogen or alkyl optionally substituted with substituent group C, or a pharmaceutically acceptable thereof Salt.
(6) B ¹ is NR ² and B ² is CR ^3a R ^3b ,
R ² is alkyl may be substituted with a substituent group C, substituted with a substituent group C which may be carbocyclic group, which may be carbocyclic aryloxy substituted with a substituent group C, substituents A heterocyclic group which may be substituted by group C, a carbocyclic alkyl which may be substituted by a substituent group C, a heterocyclic alkyl which may be substituted by a substituent group C, or -Z-C ( R ^B7 ) (R ^B8 ) (R ^B9 ),
And R ^3a is hydrogen, and R ^3b and R ⁴ together with the adjacent atoms form a heterocyclic ring which may be substituted with Substituent Group D, and further the heterocyclic ring forms a bridge. Good,
The compound according to any one of the above (1) to (4), or a pharmaceutically acceptable salt thereof.
(7) 1 R ² is a group shown below:

(Wherein, R ^E6 is selected from Substituent Group C, and m is an integer of 0 or 1 or more,
Provided that the m R ^{E 6 s} are the same or different group selected from Substituent Group C), the compound according to the above (5) or (6), or a pharmaceutically acceptable salt thereof .
(8) B ¹ is CR ^3a R ^3b and B ² is NR ² ,
R ² is hydrogen or alkyl optionally substituted with substituent group C,
R ^3a is hydrogen, R ^3b is ^optionally substituted alkyl group C, carbocyclic group ^optionally substituted group C, substituted group C Good carbocyclic ring oxyalkyl, heterocyclic group optionally substituted with substituent group C, carbocyclic alkyl optionally substituted with substituent group C, heterocyclic ring optionally substituted with substituent group C Alkyl, or -Z-C (R ^B7 ) (R ^B8 ) (R ^B9 )
Or the pharmaceutically acceptable salt thereof according to any one of (1) to (4) above.
(9) B ¹ is CR ^3a R ^3b and B ² is NR ² ,
R ^3a is hydrogen,
R ^{3 b} is alkyl ^optionally substituted with substituent group C, carbocyclic group ^optionally substituted with substituent group C, carbocyclic oxyalkyl optionally substituted with substituent group C, substituent A heterocyclic group which may be substituted by group C, a carbocyclic alkyl which may be substituted by a substituent group C, a heterocyclic alkyl which may be substituted by a substituent group C, or -Z-C ( R ^B7 ) (R ^B8 ) (R ^B9 ), and R ² and R ⁴ together with the adjacent atoms form a heterocyclic ring which may be substituted by Substituent Group D, and further the heterocyclic ring May form crosslinks,
The compound according to any one of the above (1) to (4), or a pharmaceutically acceptable salt thereof.
(10) 2R ^3b is a group shown below:

(Wherein, R ^E6 is selected from Substituent Group C, and m is an integer of 0 or 1 or more,
Provided that the m R ^{E 6 s} are the same or different group selected from Substituent Group C), the compound according to the above (8) or (9), or a pharmaceutically acceptable salt thereof .
(11) Tricyclic substituent group D is halogen, alkyl, haloalkyl, alkyloxy, carbocyclic group which may be substituted with substituent group C, heterocyclic group which may be substituted with substituent group C And any one of the above (1), (6) or (9) which is a carbocyclic alkyl which may be substituted by substituent C or a heterocyclic alkyl which may be substituted by substituent C Or a pharmaceutically acceptable salt thereof.
(12) The compound according to any one of the above (1) to (11), or a pharmaceutically acceptable salt thereof, wherein P is hydrogen.
(13) a group in which P is a group forming a prodrug, and the group forming the prodrug is selected from the following formulas a) to ac);
^{a) -C (= O) -P} R0,
^{b) -C (= O) -P} R1,
c) -C (= O) -L- ^PR1 ,
d) -C (= O) -L-O-P ^R1 ,
e) -C (= O) -L-O-L-O-P ^R1 ,
f) -C (= O) -L-O-C (= O) -P ^R1 ,
g) -C (= O) -O- ^PR2 ,
h) -C (= O) -N (-K) ( ^PR2 ),
i) -C (= O) -O-L-O- ^PR2 ,
j) -C ( ^PR3 ) _2- O- ^PR4 ;
k) -C ( ^PR3 ) _2- O-L-O- ^PR4 ,
_{^{l) -C (P R3) 2}} -O-C (= O) -P R4,
m) -C ( ^PR3 ) _2- O-C (= O) -OP- ^R4 ,
_{^{n) -C (P R3) 2}} -O-C (= O) -N (-K) -P R4,
o) -C ( ^PR3 ) _2- O-C (= O) -O-L-O- ^PR4 ,
p) -C ( ^PR3 ) _2- OC (= O) -OLN ( ^PR4 ) ₂ ,
q) -C ( ^PR3 ) _2- OC (= O) -N (-K) -LO- ^PR4 ;
r) -C ( ^PR3 ) _2- OC (= O) -N (-K) -L-N ( ^PR4 ) ₂ ,
s) -C ( ^PR3 ) _2- O-C (= O) -O-L-O-L-O- ^PR4 ,
_{^{t) -C (P R3) 2}} -O-C (= O) -O-L-N (-K) -C (= O) -P R4,
u) -C ( ^PR3 ) ₂ -OP (= O) ( ^-PR5 ) ₂ ,
_{^{v) -C (P R3) 2}} -P R6,
w)-C (= N ⁺ ( ^PR7 ) ₂ ) (-N ( ^PR7 ) ₂ ),
x) -C ( ^PR3 ) _2- C ( ^PR3 ) _2- C (= O) -O- ^PR2 ,
y) -C ( ^PR3 ) _2- N (-K) -C (= O) -O- ^PR2 ,
z)-P (= O) ( ^-PR8 ) ( ^-PR9 ),
^{_{aa) -S (= O) 2}} -P R10,
^{ab) -P R11,} and _{^{ac) -C (P R3) 2}} -C (P R3) 2 -O-P R2,
Wherein L is linear or branched alkylene, or linear or branched alkenylene,
K is hydrogen or alkyl optionally substituted with substituent group A,
P ^R0 is an alkyl which may be substituted with the substituent group A or an alkenyl which may be substituted with the substituent group A,
P ^{R 1} represents a carbocyclic group which may be substituted with substituent group A, a heterocyclic group which may be substituted with substituent group A, an alkylamino which may be substituted with substituent group A, Or alkylsulfanyl optionally substituted with substituent group A,
P ^{R 2} is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, heterocyclic alkyl which may be substituted by substituent group A, or trialkylsilyl;
P ^R3 is independently hydrogen or alkyl,
P ^{R 4} each independently represents an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a complex which may be substituted with the substituent group A Cyclic group, alkylamino which may be substituted with substituent group A, carbocyclic alkyl which may be substituted with substituent group A, heterocyclic alkyl which may be substituted with substituent group A, or tri It is alkylsilyl and
And P ^R5 is independently hydroxy or OB n
P ^R6 is a carbocyclic group which may be substituted with the substituent group A or a heterocyclic group which may be substituted with the substituent group A,
Each P ^R7 is independently an alkyl which may be substituted with Substituent Group A,
^{PR 8} is alkyloxy optionally substituted with substituent group A,
^{PR 9} is alkyloxy optionally substituted with substituent group A, alkylamino optionally substituted with substituent group A, carbocyclic ring oxy optionally substituted with substituent group A, substituent group A heterocyclic oxy which may be substituted by A, a carbocyclic amino which may be substituted by a substituent group A, or a heterocyclic amino which may be substituted by a substituent group A,
P ^R8 and P ^R9 may be taken together with the adjacent phosphorus atom to form a heterocyclic ring which may be substituted with Substituent Group A,
P ^R10 is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, or heterocyclic alkyl which may be substituted by substituent group A, and
P ^{R 11} represents an alkyl which may be substituted with the substituent group A, an alkenyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a substituent group A heterocyclic group optionally substituted by A.
Substituent group A: oxo, alkyl, hydroxyalkyl, amino, alkylamino, carbocyclic group, heterocyclic group, carbocyclic alkyl, alkylcarbonyl, halogen, hydroxy, carboxy, alkylcarbonylamino, alkylcarbonylaminoalkyl, alkyl (1) carbonyloxy, alkyloxycarbonyl, alkyloxycarbonylalkyl, alkyloxycarbonyloxy, alkylaminocarbonyloxy, alkylaminoalkyl, alkyloxy, cyano, nitro, azide, alkylsulfonyl, trialkylsilyl, and phospho (s) mentioned above (1) ) The compound in any one of-(11), or its pharmaceutically acceptable salt.
(14) An antiviral agent comprising the compound according to any one of the above (1) to (13), a pharmaceutically acceptable salt thereof, or a solvate thereof.
(15) The antiviral agent according to the above (14), which has anti-influenza activity.
(16) The compound according to any one of the above (1) to (13) for the treatment and / or prevention of influenza infection.
(17) Treatment and / or treatment of influenza infection, which comprises administering a compound according to any one of (1) to (13) above, a pharmaceutically acceptable salt thereof, or a solvate thereof How to prevent.
(18) The antiviral agent according to the above (14), which has cap-dependent endonuclease inhibitory activity.
(19) Treatment of a disease caused by a virus having a cap-dependent endonuclease, which comprises administering the compound according to any one of the above (1) to (13), or a pharmaceutically acceptable salt thereof Or preventive methods.
(20) The compound according to any one of the above (1) to (13), or a pharmaceutically acceptable salt thereof, for producing a therapeutic or prophylactic agent for a disease caused by a virus having a cap-dependent endonuclease Use of.
(21) An antiviral agent for oral administration, which comprises the compound according to any one of the above (1) to (13), or a pharmaceutically acceptable salt thereof.
(22) Tablets, powders, granules, capsules, pills, films, suspensions, emulsions, elixirs, syrups, limonades, liquor spirits, aromatic liquids, extracts, decoctions or decoctions or tinctures , (21) described antiviral agent.
(23) Sugar coated tablets, film coated tablets, enteric coated tablets, sustained release tablets, troche tablets, sublingual tablets, buccal tablets, chewable tablets, orally disintegrating tablets, dry syrup, soft capsules, microcapsules or sustained release capsules (21) The antiviral agent according to (21).
(24) An antiviral agent for parenteral administration, which comprises the compound according to any one of the above (1) to (13), or a pharmaceutically acceptable salt thereof.
(25) The antiviral agent according to (24) for percutaneous, subcutaneous, intravenous, intraarterial, intramuscular, intraperitoneal, transmucosal, inhalation, nasal, eye drops, ear drops or vaginal administration.
(26) Injections, drips, eye drops, nasal drops, ear drops, aerosols, inhalants, lotions, injections, coatings, gargles, enemas, ointments, plasters, jellies, The antiviral agent according to (24) or (25), which is a cream, a patch, a patch, an external use powder or a suppository.
(27) An antiviral agent for children or elderly people, which comprises the compound according to any one of the above (1) to (13), or a pharmaceutically acceptable salt thereof.
(28) The compound according to any one of the above (1) to (13), or a pharmaceutically acceptable salt thereof, a neuraminidase inhibitor, an RNA-dependent RNA polymerase inhibitor, an M2 protein inhibitor, a PB2 Cap binding inhibition An antiviral agent which comprises an agent, an anti-HA antibody, or a combination with an immunological agent.
(29) A neuraminidase inhibitor, an RNA-dependent RNA polymerase inhibitor, an M2 protein inhibitor, or a PB2 Cap comprising the compound according to any one of the above (1) to (13), or a pharmaceutically acceptable salt thereof. An antiviral agent for combination therapy with a binding inhibitor, an anti-HA antibody, or an immunological agent.

  The present invention further provides a method for treating or preventing influenza infection using a prodrug compound, as well as the above-mentioned compound having anti-influenza activity. The invention further provides parent compounds of prodrug compounds. The parent compound is useful as an anti-influenza agent or an intermediate of the prodrug compound.

  The compounds according to the invention have an inhibitory activity on cap-dependent endonucleases. The more preferable compounds are prodrugs, and after administration, they become parent compounds having an inhibitory activity against cap-dependent endonuclease in the body, and thus they are useful as therapeutic agents and / or preventive agents for influenza infection.

The meanings of the terms used in the present specification will be described below. Unless otherwise noted, each term is used in the same meaning whether used alone or in combination with other terms.
The term "consisting of" means having only compositional requirements.
The term "comprising" is not limited to compositional terms and means not excluding elements not described.

The term "optionally substituted with Substituent Group A" means that one or more identical or different substituents selected from Substituent Group A may be substituted at any position.
The same applies to “optionally substituted with substituent group C” and “optionally substituted with substituent group D”.

（式中、Ｐ^Ｒはプロドラッグを形成する基であり、各記号は上記と同意義である）
における式（ＩＩ）で示される化合物またはその製薬上許容される塩を指し、生体内における生理条件下で薬物代謝酵素、加水分解酵素、胃酸、腸内細菌等によって引き起こされる分解反応によって、それぞれ式（ＩＩＩ）で示される化合物に変換されることにより、キャップ依存的エンドヌクレアーゼ（ＣＥＮ）阻害活性、および／またはＣＰＥ抑制効果を示す化合物を意味する。
該プロドラッグは、より好ましくは、式（ＩＩＩ）で示される化合物よりも、生体内投与時におけるバイオアベイラビリティおよび／またはＡＵＣ（血中濃度曲線下面積）が向上している化合物を意味する。
したがって、該プロドラッグは、生体への投与（例えば、経口投与）後に、胃および／または腸等で効率よく体内に吸収され、その後、式（ＩＩＩ）で示される化合物に変換されるため、好ましくは、式（ＩＩＩ）で示される化合物よりも高いインフルエンザ治療および／または予防効果を示す。 The term "prodrug" as used herein refers to the following reaction formula:

( ^Wherein , P ^R is a group forming a prodrug, and each symbol is as defined above)
The compound represented by the formula (II) or a pharmaceutically acceptable salt thereof according to the present invention, each of which is represented by a degradation reaction caused by drug metabolizing enzyme, hydrolytic enzyme, gastric acid, enteric bacteria etc under physiological conditions in vivo By converting into a compound represented by (III), it means a compound that exhibits a cap-dependent endonuclease (CEN) inhibitory activity and / or a CPE inhibitory effect.
The prodrug more preferably means a compound having improved bioavailability and / or AUC (area under the blood concentration curve) at the time of in vivo administration more than the compound represented by the formula (III).
Therefore, the prodrug is preferably absorbed into the body efficiently in the stomach and / or intestine after administration to a living body (for example, oral administration), and then converted to the compound represented by formula (III). Has a higher influenza therapeutic and / or prophylactic effect than the compounds of formula (III).

（式中、各記号は上記と同意義である）
の、式（ＩＩ）における「Ｐ^Ｒ」基を指し、−ＯＰ^Ｒ基の部分が、生体内における生理条件下で薬物代謝酵素、加水分解酵素、胃酸、腸内細菌等によって引き起こされる分解反応によって、式（ＩＩＩ）における−ＯＨ基に変換される基を示す。
該「プロドラッグを形成する基」は、より好ましくは、式（ＩＩＩ）で示される化合物に付加することによって、式（ＩＩＩ）で示される化合物のバイオアベイラビリティおよび／またはＡＵＣ（血中濃度曲線下面積）を向上させる基を意味する。 The “prodrug forming group” in the present specification is the following reaction formula:

(Wherein each symbol is as defined above)
Of, refers to "P ^R" groups in Formula (II), part of the -OP ^R groups, drug-metabolizing enzyme in vivo under physiological conditions, hydrolysis enzyme, gastric acid, the decomposition reaction caused by the intestinal bacteria, etc. The group converted into -OH group in Formula (III) is shown.
More preferably, the “prodrug forming group” is added to the compound represented by the formula (III) to obtain the bioavailability and / or the AUC (blood concentration curve) of the compound represented by the formula (III). Means a group that improves the area).

As groups forming a prodrug, for example, Prog. Med. 5: 2157-2161 (1985), and Supplied by The British Library-groups described in "The world's Knowledge".
The “P ^R ” group of the formula (I) or the formula (II) may be a group which converts the —OP ^R group into an —OH group in vivo, preferably, for example, the following formula a) to ac) And a group selected from
^{a) -C (= O) -P} R0,
^{b) -C (= O) -P} R1,
c) -C (= O) -L- ^PR1 ,
d) -C (= O) -L-O-P ^R1 ,
e) -C (= O) -L-O-L-O-P ^R1 ,
f) -C (= O) -L-O-C (= O) -P ^R1 ,
g) -C (= O) -O- ^PR2 ,
h) -C (= O) -N (-K) ( ^PR2 ),
i) -C (= O) -O-L-O- ^PR2 ,
j) -C ( ^PR3 ) _2- O- ^PR4 ;
k) -C ( ^PR3 ) _2- O-L-O- ^PR4 ,
_{^{l) -C (P R3) 2}} -O-C (= O) -P R4,
m) -C ( ^PR3 ) _2- O-C (= O) -OP- ^R4 ,
_{^{n) -C (P R3) 2}} -O-C (= O) -N (-K) -P R4,
o) -C ( ^PR3 ) _2- O-C (= O) -O-L-O- ^PR4 ,
p) -C ( ^PR3 ) _2- OC (= O) -OLN ( ^PR4 ) ₂ ,
q) -C ( ^PR3 ) _2- OC (= O) -N (-K) -LO- ^PR4 ;
r) -C ( ^PR3 ) _2- OC (= O) -N (-K) -L-N ( ^PR4 ) ₂ ,
s) -C ( ^PR3 ) _2- O-C (= O) -O-L-O-L-O- ^PR4 ,
_{^{t) -C (P R3) 2}} -O-C (= O) -O-L-N (-K) -C (= O) -P R4,
u) -C ( ^PR3 ) ₂ -OP (= O) ( ^-PR5 ) ₂ ,
_{^{v) -C (P R3) 2}} -P R6,
w)-C (= N ⁺ ( ^PR7 ) ₂ ) (-N ( ^PR7 ) ₂ ),
x) -C ( ^PR3 ) _2- C ( ^PR3 ) _2- C (= O) -O- ^PR2 ,
y) -C ( ^PR3 ) _2- N (-K) -C (= O) -O- ^PR2 ,
z)-P (= O) ( ^-PR8 ) ( ^-PR9 ),
^{_{aa) -S (= O) 2}} -P R10,
^{ab) -P R11,} and _{^{ac) -C (P R3) 2}} -C (P R3) 2 -O-P R2,
Wherein L is linear or branched alkylene, or linear or branched alkenylene,
K is hydrogen or alkyl optionally substituted with substituent group A,
P ^R0 is an alkyl which may be substituted with the substituent group A or an alkenyl which may be substituted with the substituent group A,
P ^{R 1} represents a carbocyclic group which may be substituted with substituent group A, a heterocyclic group which may be substituted with substituent group A, an alkylamino which may be substituted with substituent group A, Or alkylsulfanyl optionally substituted with substituent group A,
P ^{R 2} is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, heterocyclic alkyl which may be substituted by substituent group A, or trialkylsilyl;
And each P ^R3 is independently hydrogen or alkyl,
P ^{R 4} each independently represents an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a complex which may be substituted with the substituent group A Cyclic group, alkylamino which may be substituted with substituent group A, carbocyclic alkyl which may be substituted with substituent group A, heterocyclic alkyl which may be substituted with substituent group A, or tri It is alkylsilyl and
And P ^R5 is independently hydroxy or OB n
P ^R6 is a carbocyclic group which may be substituted with the substituent group A or a heterocyclic group which may be substituted with the substituent group A,
Each P ^R7 is independently an alkyl which may be substituted with Substituent Group A,
^{PR 8} is alkyloxy optionally substituted with substituent group A,
^{PR 9} is alkyloxy optionally substituted with substituent group A, alkylamino optionally substituted with substituent group A, carbocyclic ring oxy optionally substituted with substituent group A, substituent group A heterocyclic oxy which may be substituted by A, a carbocyclic amino which may be substituted by a substituent group A, or a heterocyclic amino which may be substituted by a substituent group A,
P ^R8 and P ^R9 may be taken together with the adjacent phosphorus atom to form a heterocyclic ring which may be substituted with Substituent Group A,
P ^R10 is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, or heterocyclic alkyl which may be substituted by substituent group A,
P ^{R 11} represents an alkyl which may be substituted with the substituent group A, an alkenyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a substituent group A heterocyclic group optionally substituted by A.
Substituent group A: oxo, alkyl, hydroxyalkyl, amino, alkylamino, carbocyclic group, heterocyclic group, carbocyclic alkyl, alkylcarbonyl, halogen, hydroxy, carboxy, alkylcarbonylamino, alkylcarbonylaminoalkyl, alkyl Carbonyloxy, alkyloxycarbonyl, alkyloxycarbonylalkyl, alkyloxycarbonyloxy, alkylaminocarbonyloxy, alkylaminoalkyl, alkyloxy, cyano, nitro, azide, alkylsulfonyl, trialkylsilyl, and phospho).

The group forming the prodrug is preferably a group selected from the following groups.
^{a) -C (= O) -P} R0,
^{b) -C (= O) -P} R1,
g) -C (= O) -O- ^PR2 ,
h) -C (= O) -N (-K) ( ^PR2 ),
i) -C (= O) -O-L-O- ^PR2 ,
_{^{l) -C (P R3) 2}} -O-C (= O) -P R4,
m) -C ( ^PR3 ) _2- O-C (= O) -OP- ^R4 ,
o) -C ( ^PR3 ) _2- O-C (= O) -O-L-O- ^PR4 ,
_{^{v) -C (P R3) 2}} -P R6,
x) -C ( ^PR3 ) _2- C ( ^PR3 ) _2- C (= O) -O- ^PR2 ,
y) -C ( ^PR3 ) _2- N (-K) -C (= O) -O- ^PR2 , and z) -P (= O) ( ^-PR8 ) ( ^-PR9 ),
Wherein L is a linear or branched alkylene,
K is hydrogen or alkyl optionally substituted with substituent group A,
P ^R0 is alkyl ^optionally substituted with Substituent Group A,
P ^R1 is a carbocyclic group which may be substituted with substituent group A or a heterocyclic group which may be substituted with substituent group A,
P ^{R 2} is each independently an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a complex which may be substituted with the substituent group A A cyclic group, a carbocyclic alkyl which may be substituted with substituent group A, or a heterocyclic alkyl which may be substituted with substituent group A,
And each P ^R3 is independently hydrogen or alkyl,
P ^{R 4} represents an alkyl which may be substituted with substituent group A, a carbocyclic group which may be substituted with substituent group A, or a heterocyclic group which may be substituted with substituent group A Yes,
P ^R6 is a carbocyclic group which may be substituted with the substituent group A or a heterocyclic group which may be substituted with the substituent group A,
^{PR 8} is alkyloxy optionally substituted with substituent group A,
^{PR 9} is alkyloxy optionally substituted with substituent group A, alkylamino optionally substituted with substituent group A, carbocyclic ring oxy optionally substituted with substituent group A, substituent group Heterocyclic ring optionally substituted with A, carbocyclic amino optionally substituted with substituent group A, or heterocyclic amino optionally substituted with substituent group A, and ^{PR 8} and P ^{R 9} may be taken together with the adjacent phosphorus atom to form a heterocyclic ring which may be substituted with Substituent Group A.
Substituent group A: oxo, alkyl, alkylamino, carbocyclic group, heterocyclic group, alkylcarbonyl, halogen, hydroxy, alkylcarbonylamino, alkylcarbonyloxy, alkyloxycarbonyl, alkyloxycarbonylalkyl, alkylaminocarbonyloxy (Alkyloxy, nitro, azide, alkylsulfonyl and trialkylsilyl).

（式中、各記号は上記と同意義である）
に示されるように、式（ＩＩＩ）またはその製薬上許容される塩のヒドロキシ基を、−ＯＰ^Ｒ基に変換することを意味する。 In the present specification, “prodrugation” is the following reaction formula:

(Wherein each symbol is as defined above)
As shown in Figure 5, it means converting the hydroxy group of formula (III) or a pharmaceutically acceptable salt thereof into a -OP ^R group.

  In the present specification, the “parent compound” refers to a compound serving as a raw material before synthesizing the “prodrug” and / or release from the “prodrug” by a reaction by an enzyme, gastric acid or the like under physiological conditions in vivo. And the compound represented by the above-mentioned formula (III), or a pharmaceutically acceptable salt thereof.

  The "halogen" includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. In particular, a fluorine atom and a chlorine atom are preferred.

The term "alkyl" includes straight or branched hydrocarbon groups having 1 to 15 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms, and 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. Further preferred embodiments include methyl, ethyl, n-propyl, isopropyl and tert-butyl.

"Alkenyl" means one having 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, and still more preferably 2 to 4 carbon atoms, having one or more double bonds at any position. And 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, dodecenyl, tridecenyl, tetradecenyl, etc. Etc.
Preferred embodiments of "alkenyl" include vinyl, allyl, propenyl, isopropenyl and butenyl.

  "Alkylene" means 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 more preferably 1 to 4 carbon atoms Include groups. For example, methylene, ethylene, trimethylene, propylene, tetramethylene, pentamethylene, hexamethylene and the like can be mentioned.

  "Alkenylene" means one having 2 to 15 carbon atoms, preferably 2 to 10 carbon atoms, more preferably 2 to 6 carbon atoms, and still more preferably 2 to 4 carbon atoms, having one or more double bonds at any position. And a linear or branched divalent hydrocarbon group of For example, vinylene, propenylene, butenylene, pentenylene and the like can be mentioned.

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３〜８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、フルオレニル等および以下に示される基が挙げられる。

The “carbocyclic group” means a carbocyclic group having 3 to 20 carbon atoms, preferably 3 to 16 carbon atoms, more preferably 4 to 12 carbon atoms, and is preferably an aromatic carbocyclic group and a nonaromatic group. Includes carbocyclic groups.
The "aromatic carbocyclic group" includes a monocyclic or two or more cyclic aromatic hydrocarbon group. For example, phenyl, naphthyl, anthryl, phenanthryl and the like can be mentioned.
One embodiment of the "aromatic carbocyclic group" includes phenyl, 1-naphthyl and 2-naphthyl. Another embodiment includes phenyl.
Etc.
The "non-aromatic carbocyclic group" includes a monocyclic or two or more cyclic saturated hydrocarbon group or a cyclic non-aromatic unsaturated hydrocarbon group. The “two or more non-aromatic carbocyclic groups” also include those in which the ring in the above “aromatic carbocyclic group” is fused to a single ring or two or more non-aromatic carbocyclic groups.
Furthermore, "non-aromatic carbocyclic group" also includes a cyclic group which is bridged as follows, or a cyclic group which 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 still more preferably 3 to 8 carbon atoms. For example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclohexadienyl and the like.
The nonaromatic carbocyclic group having two or more rings preferably has 8 to 20 carbon atoms, and more preferably 8 to 16 carbon atoms. Examples include indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, fluorenyl and the like and the groups shown below.

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、アセナフタレン、テトラヒドロナフタレン、フルオレン等が挙げられる。 "Carbocycle" means a carbocycle having 3 to 20 carbon atoms, preferably 3 to 16 carbon atoms, more preferably 4 to 12 carbon atoms, and includes aromatic carbocycles and non-aromatic carbocycles.
The "aromatic carbocyclic ring" includes a monocyclic or two or more cyclic aromatic hydrocarbon. For example, a benzene ring, a naphthalene ring, an anthracene ring, a phenanthrene ring and the like can be mentioned.
A benzene ring and a naphthalene ring are mentioned as one aspect of "aromatic carbocyclic ring." Another embodiment includes a benzene ring.
The "non-aromatic carbocyclic ring" includes a monocyclic or two or more cyclic saturated hydrocarbon or cyclic non-aromatic unsaturated hydrocarbon. The “two or more non-aromatic carbocyclic rings” also include those in which the ring in the above “aromatic carbocyclic ring” is fused to a single ring or two or more non-aromatic carbocyclic rings.
Furthermore, "non-aromatic carbocyclic ring" also includes a ring bridged as follows or a ring forming a spiro ring.

The monocyclic non-aromatic carbon ring preferably has 3 to 16 carbon atoms, more preferably 3 to 12 carbon atoms, and still more 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.
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, acenaphthalene, tetrahydronaphthalene, fluorene and the like can be mentioned.

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８〜１６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、イソクロマニル等および以下に示される基が挙げられる。

"Heterocyclic group" includes aromatic heterocyclic group and non-aromatic heterocyclic group having in the ring one or more identical or different heteroatoms optionally selected from O, S and N .
The “aromatic heterocyclic group” includes a monocyclic or two or more aromatic cyclic group having one or more identical or different hetero atoms optionally selected from O, S and N in the ring. Do.
The “aromatic heterocyclic group” having two or more rings also includes one in which a ring in the above “aromatic carbocyclic group” is fused to a monocyclic or two or more aromatic heterocyclic group.
The monocyclic aromatic heterocyclic group preferably has 5 to 8 members, more preferably 5 or 6 members. For example, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazolyl, triazinyl, triazolyl, furyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl and the like.
The two-ring aromatic heterocyclic group is preferably 8 to 10 members, more preferably 9 members or 10 members. For example, indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazole Ryl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, thiazolopyridyl etc. Can be mentioned.
Examples of the aromatic heterocyclic group having 3 or more rings include carbazolyl, acridinyl, xanthenyl, phenothiazinyl, phenoxatyinyl, phenoxazinyl, dibenzofuryl and the like.
The “non-aromatic heterocyclic group” is a monocyclic or two or more cyclic non-aromatic cyclic group having one or more identical or different hetero atoms optionally selected from O, S and N in the ring. Include groups.
The “nonaromatic heterocyclic group” having two or more rings is a single ring or a nonaromatic heterocyclic group having two or more rings, and the above “aromatic carbocyclic group”, “nonaromatic carbocyclic group” And / or ones in which the respective rings in the "aromatic heterocyclic group" are fused are also included.
Furthermore, "non-aromatic heterocyclic group" also includes a group which is bridged as follows or a group which forms a spiro ring.

As a monocyclic non-aromatic heterocyclic group, 3 to 8 members are preferable, and more preferably 5 or 6 members. For example, dioxanyl, thiiranyl, oxiranyl, oxetanyl, oxathiolanyl, azetidinyl, thiazolyl, thiazolidinyl, pyrrolidinyl, pyrrolidinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidyl, piperazinyl, morpholinyl, morpholino, thiomorpholino, thiomorpholino, dihydropyridyl, tetrahydropyridyl Furyl, tetrahydropyranyl, dihydrothiazolyl, tetrahydrothiazolyl, tetrahydroisothiazolyl, dihydrooxazinyl, hexahydroazepinyl, tetrahydrodiazepinyl, tetrahydropyridazinyl, hexahydropyrimidinyl, dioxolanyl, dioxazinyl , Aziridinyl, dioxolinyl, oxepanyl, thiolanil, thiy Le, triazinyl, and the like.
The non-aromatic heterocyclic group having 2 or more rings is preferably 8 to 20 members, more preferably 8 to 16 members. Examples include indolinyl, isoindolinyl, chromanyl, isochromanyl and the like and the groups shown below.

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 “heterocycle” includes aromatic heterocycles and non-aromatic heterocycles having one or more identical or different heteroatoms optionally selected from O, S and N in the ring.
The "aromatic heterocycle" includes a single ring or two or more aromatic rings having one or more identical or different heteroatoms optionally selected from O, S and N in the ring.
The “aromatic heterocycle” having two or more rings also includes one in which the ring in the above “aromatic carbocyclic ring” is fused to a monocyclic or two or more aromatic heterocycle.
As a monocyclic aromatic heterocycle, 5-8 members are preferable, More preferably, they are 5 members 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.
As a 2-ring aromatic heterocyclic ring, 8-10 members are preferable, More preferably, they are 9 members or 10 members. For example, indole, isoindole, indazole, indolizine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, naphthyridine, quinoxaline, purine, pteridine, benzimidazole, benzisoxazole, benzoxazole, benzoxadiazole, benzisothiazole, benzo Thiazole, benzothiadiazole, benzofuran, isobenzofuran, benzothiophene, benzotriazole, imidazopyridine, triazolopyridine, imidazothiazole, pyrazinopyridazine, oxazolopyridine, thiazolopyridine and the like.
The aromatic heterocyclic ring having three or more rings is preferably 11 to 26 members, more preferably 13 or 14 members. For example, carbazole, acridine, xanthene, phenothiazine, phenoxathiin, phenoxazine, dibenzofuran and the like can be mentioned.
The “non-aromatic heterocyclic ring” is a monocyclic or two or more cyclic non-aromatic ring having one or more identical or different hetero atoms optionally selected from an oxygen atom, a sulfur atom and a nitrogen atom in the ring Includes
The “non-aromatic heterocycle” having two or more rings is a single ring or two or more non-aromatic heterocycles, and the above “aromatic carbocyclic ring”, “non-aromatic carbocyclic ring”, and / or “aromatic heteroaromatic ring” Also included are those in which each ring in “ring” is fused.
Furthermore, "non-aromatic heterocycle" also includes rings that are bridged as follows, or rings that form a spiro ring.

As a single ring non-aromatic heterocyclic ring, 3-8 members are preferable, More preferably, they are 5 members or 6 members. For example, dioxane, thiirane, oxirane, oxetane, oxathiolane, azetidine, thiane, thiazolidine, pyrrolidine, pyrroline, imidazoline, imidazoline, pyrazolidine, pyrazoline, piperidine, piperazine, morpholine, thiomorpholine, dihydropyridine, tetrahydropyridine, tetrahydrofuran, tetrahydropyran, Dihydrothiazole, tetrahydrothiazole, tetrahydroisothiazole, dihydrooxazine, hexahydroazepine, tetrahydrodiazepine, tetrahydropyridazine, hexahydropyrimidine, dioxolane, dioxazine, aziridine, dioxole, oxepane, thiolane, thiine, thiazine and the like.
As a 2 or more non-aromatic heterocyclic ring, 8-20 members are preferable and it is 8-10 members. For example, indoline, isoindoline, chroman, isochroman and the like can be mentioned.

（式中、各記号は上記と同意義である。）
を表わし、環の部分が１または２以上の置換基群Ｄから選択される同一または異なる置換基で任意の位置で置換されていてもよいことを示す。該複素環は、好ましくは５〜７員環である。また、該複素環は縮合環を形成していてもよく、式（ＩＡ）における環がさらに縮環していてもよいことを示し、置換基群Ｄは、上記式（ＩＡ）における環または縮環している環のいずれにも結合していてもよいことを示す。
式（ＩＡ）の例として、以下の式に示す化合物

（式中、Ｒ^ｘ、およびＲ^ｙは、置換基群Ｄから選択される置換基であり、その他の記号は上記と同意義である。）等が挙げられる。 “R ^{3 b} and R ⁴ may be taken together with the adjacent atom to form a heterocyclic ring which may be substituted with Substituent Group D” is a group of the formula (IA) shown below:

(In the formula, each symbol is as defined above.)
And that part of the ring may be substituted at any position with the same or different substituent selected from one or more substituent group D. The heterocycle is preferably a 5- to 7-membered ring. The heterocycle may form a fused ring, and it is shown that the ring in the formula (IA) may be further condensed, and the substituent group D is a ring or a fused in the above formula (IA) It shows that it may be bonded to any of the ring rings.
Compounds represented by the following formula as an example of formula (IA)

(Wherein, R ^x and R ^y are substituents selected from Substituent Group D, and the other symbols are as defined above) and the like.

（式中、Ａ^１は、それぞれ独立してＣＲ^１ＡＲ^１Ｂ、ＳまたはＯ；
Ａ^２は、ＣＲ^２Ａ；
Ａ^３は、それぞれ独立してＣＲ^３ＡＲ^３Ｂ、ＳまたはＯ；
Ａ^４は、ＣＲ^４；
Ａ^５は、それぞれ独立してＣＲ^５ＡＲ^５Ｂ、ＳまたはＯ；
Ａ^６は、単結合、または置換もしくは非置換のヘテロ原子を介在していてもよいアルキレン；
ここで、Ａ^１、Ａ^２、Ａ^３、Ａ^４、Ａ^５、Ａ^１に隣接する窒素原子、およびＡ^５に隣接する炭素原子から構成される環の環構成原子のヘテロ原子の数は、１または２個であり；
Ｒ^１Ａは、それぞれ独立して、水素、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、またはフェニル；
Ｒ^１Ｂは、それぞれ独立して、水素、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、またはフェニル；
Ｒ^２Ａは、水素、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、またはフェニル；
Ｒ^３Ａは、それぞれ独立して、水素、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、またはフェニル；
Ｒ^３Ｂは、それぞれ独立して、水素、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、またはフェニル；
Ｒ^４Ａは、水素、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、またはフェニル；
Ｒ^５Ａは、それぞれ独立して、水素、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、またはフェニル；
Ｒ^５Ｂは、それぞれ独立して、水素、ハロゲン、アルキル、ハロアルキル、アルキルオキシ、またはフェニル；
Ｒ^１ＡおよびＲ^１Ｂは隣接する炭素原子と一緒になって、置換基群Ｃで置換されていてもよい炭素環または置換基群Ｃで置換されていてもよい複素環を形成してもよく；
Ｒ^３ＡおよびＲ^３Ｂは隣接する炭素原子と一緒になって、置換基群Ｃで置換されていてもよい炭素環または置換基群Ｃで置換されていてもよい複素環を形成してもよく；
Ｒ^５ＡおよびＲ^５Ｂは隣接する炭素原子と一緒になって、置換基群Ｃで置換されていてもよい炭素環または置換基群Ｃで置換されていてもよい複素環を形成してもよく、該炭素環または複素環はさらに架橋されていてもよい；
ｐは０から２の整数であり；
ｑは１から２の整数であり；
ｒは０から２の整数であり；その他の各記号は、上記と同異議である。）を表わす。
（ＩＢ）における、「Ａ^６は、単結合、または置換もしくは非置換のヘテロ原子を介在していてもよいアルキレン」の「Ａ^６は単結合」とは、以下に示す式（ＩＢ’）：

で示される化合物を示す。
また、式（ＩＢ）における、「Ａ^６は、単結合、または置換もしくは非置換のヘテロ原子を介在していてもよいアルキレン」の「置換もしくは非置換のヘテロ原子を介在していてもよいアルキレン」とは、上記「アルキル」で置換されていてもよいヘテロ原子が、１〜２個介在してもよい炭素数１〜６の直鎖状又は分枝状のアルキレンを包含し、例えば、−ＣＨ_２−、−ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２Ｏ−、−ＯＣＨ_２−、−ＣＨ_２ＣＨ_２Ｏ−、−ＯＣＨ_２ＣＨ_２−、−ＣＨ_２Ｓ−、−ＳＣＨ_２−、−ＣＨ_２ＣＨ２_Ｓ−、−ＳＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ２ＯＣＨ_２ＣＨ_２−、−ＯＣＨ_２ＣＨ_２Ｏ−、−ＯＣＨ_２Ｏ−、−ＮＨＣＨ_２−、−Ｎ（ＣＨ_３）ＣＨ_２−、−Ｎ^＋（ＣＨ_３）_２ＣＨ_２−、−ＮＨＣＨ_２ＣＨ_２ＣＨ_２−、−Ｎ（ＣＨ_３）ＣＨ_２ＣＨ_２ＣＨ_２−等が挙げられる。好ましくは、−ＣＨ_２−、−ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２−、−ＯＣＨ_２ＣＨ_２Ｏ−、−ＯＣＨ_２Ｏ−、−Ｎ（ＣＨ_３）ＣＨ_２ＣＨ_２ＣＨ_２−が挙げられる。
式（ＩＢ）の例として、以下の式に示す化合物

（式中、各記号は上記と同意義である。）等が挙げられる。 B ¹ is NR ² and B ² is CR ^3a R ^3b , and R ^3b and R ⁴ are taken together with their adjacent atoms to form a heterocyclic ring which may be substituted by Substituent Group D , “Furthermore, the heterocycle may form a bridge” is a compound of the following formula (IB):

(Wherein, A ¹ is each independently CR ^1A R ^1B , S or O;
A ² is CR ^2A ;
A ³ is each independently CR ^3A R ^3B , S or O;
A ⁴ is CR ⁴ ;
A ⁵ is independently CR ^5A R ^5B , S or O;
A ⁶ represents a single bond or an alkylene optionally having a substituted or unsubstituted heteroatom;
Here, the number of heteroatoms in the ring-constituting atoms composed of a nitrogen atom adjacent to A ¹ , A ² , A ³ , A ⁴ , A ⁵ and A ¹ and a carbon atom adjacent to A ⁵ is 1 or 2 pieces;
R ^1A is each independently hydrogen, halogen, alkyl, haloalkyl, alkyloxy or phenyl;
R ^1B is each independently hydrogen, halogen, alkyl, haloalkyl, alkyloxy or phenyl;
R ^2A is hydrogen, halogen, alkyl, haloalkyl, alkyloxy or phenyl;
R ^3A is each independently hydrogen, halogen, alkyl, haloalkyl, alkyloxy or phenyl;
R ^3B is each independently hydrogen, halogen, alkyl, haloalkyl, alkyloxy or phenyl;
R ^4A is hydrogen, halogen, alkyl, haloalkyl, alkyloxy or phenyl;
R ^5A is each independently hydrogen, halogen, alkyl, haloalkyl, alkyloxy or phenyl;
R ^5B is each independently hydrogen, halogen, alkyl, haloalkyl, alkyloxy or phenyl;
R ^1A and R ^1B may be taken together with the adjacent carbon atom to form a carbon ring which may be substituted with substituent group C or a heterocyclic ring which may be substituted with substituent group C;
R ^3A and R ^3B may be taken together with the adjacent carbon atom to form a carbon ring which may be substituted with substituent group C or a heterocyclic ring which may be substituted with substituent group C;
R ^5A and R ^5B may be taken together with the adjacent carbon atom to form a carbon ring which may be substituted with substituent group C or a heterocyclic ring which may be substituted with substituent group C, The carbocycle or heterocycle may be further bridged;
p is an integer of 0 to 2;
q is an integer of 1 to 2;
r is an integer from 0 to 2; each other symbol is as above. Represents.
In (IB), "A ⁶ represents a single bond, or a substituted or unsubstituted alkylene which may have an intervening hetero atom" as of "A ⁶ represents a single bond", given by the following Expression (IB '):

The compound shown by these is shown.
Further, in the formula (IB), “A ⁶ may be a single bond, or an alkylene which may have a substituted or unsubstituted hetero atom”, may be a “substituted or unsubstituted hetero atom of an alkylene”. “Includes a linear or branched alkylene having 1 to 6 carbon atoms in which one or two hetero atoms optionally substituted by the above“ alkyl ”may be intervened, for example, _{CH 2 -, - CH 2 CH} 2 -, - CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH _{2 CH 2 CH 2 CH 2 -} , - CH 2 O -, - OCH 2 -, - CH 2 CH 2 O -, - OCH 2 CH 2 -, - CH 2 S -, - SCH 2 -, - CH 2 CH2 _S −, −SCH ₂ CH ₂ −, −CH _{2 CH2OCH 2 CH 2 -, -} OCH 2 CH 2 O -, - OCH 2 O -, - NHCH 2 -, - N (CH 3) CH 2 -, - N + (CH 3) 2 CH 2 -, - NHCH _{2 CH 2 CH 2 -, -} N (CH 3) CH 2 CH 2 CH 2 - and the like. _{Preferably, -CH 2 -, - CH 2} CH 2 -, - CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 -, - OCH 2 CH 2 O -, - OCH 2 O -, - _{N (CH 3) CH 2 CH} 2 CH 2 - and the like.
Compounds represented by the following formula as an example of formula (IB)

(Wherein each symbol is as defined above) and the like.

（式中、各記号は上記と同意義である。）
を表わし、環の部分が１または２以上の置換基群Ｄから選択される同一または異なる置換基で任意の位置で置換されていてもよいことを示す。該炭素環は、好ましくは３〜７員環である。該複素環は、好ましくは４〜７員環である。式（ＩＣ）の例として、以下の式に示す化合物

（式中、各記号は上記と同意義である。）等が挙げられる。 “R ^3a and R ^3b may be taken together with adjacent atoms to form a carbocyclic ring or heterocyclic ring which may be substituted with Substituent Group D” is a formula (IC) shown below :

(In the formula, each symbol is as defined above.)
And that part of the ring may be substituted at any position with the same or different substituent selected from one or more substituent group D. The carbocycle is preferably a 3-7 membered ring. The heterocycle is preferably a 4 to 7 membered ring. As an example of the formula (IC), a compound represented by the following formula

(Wherein each symbol is as defined above) and the like.

（式中、各記号は上記と同意義である。）
を表わし、環の部分が１または２以上の置換基群Ｄから選択される同一または異なる置換基で任意の位置で置換されていてもよいことを示す。該複素環は、好ましくは５〜７員環である。また、該複素環は縮合環を形成していてもよく、式（ＩＤ）における環がさらに縮環していてもよいことを示し、置換基群Ｄは、上記式（ＩＤ）における環または縮環している環のいずれにも結合していてもよいことを示す。
式（ＩＤ）の例として、以下の式に示す化合物

（式中、各記号は上記と同意義である。）等が挙げられる。 “R ² and R ⁴ may be combined with adjacent atoms to form a heterocyclic ring which may be substituted with Substituent Group D” is represented by the formula (ID) shown below:

(In the formula, each symbol is as defined above.)
And that part of the ring may be substituted at any position with the same or different substituent selected from one or more substituent group D. The heterocycle is preferably a 5- to 7-membered ring. The heterocyclic ring may form a fused ring, and it is shown that the ring in the formula (ID) may be further condensed, and the substituent group D is a ring or a fused ring in the above formula (ID) It shows that it may be bonded to any of the ring rings.
Compounds represented by the following formula as an example of formula (ID)

(Wherein each symbol is as defined above) and the like.

（式中、各記号は上記と同意義である。）を表わす。
（ＩＥ）における、「Ａ^６は、単結合、または置換もしくは非置換のヘテロ原子を介在していてもよいアルキレン」の「Ａ^６は単結合」とは、以下に示す式（ＩＥ’）：

で示される化合物を示す。
また、式（ＩＥ’）における、「Ａ^６は、単結合、または置換もしくは非置換のヘテロ原子を介在していてもよいアルキレン」の「置換もしくは非置換のヘテロ原子を介在していてもよいアルキレン」とは、上記「アルキル」で置換されていてもよいヘテロ原子が、１〜２個介在してもよい炭素数１〜６の直鎖状又は分枝状のアルキレンを包含し、例えば、−ＣＨ_２−、−ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２Ｏ−、−ＯＣＨ_２−、−ＣＨ_２ＣＨ_２Ｏ−、−ＯＣＨ_２ＣＨ_２−、−ＣＨ_２Ｓ−、−ＳＣＨ_２−、−ＣＨ_２ＣＨ２_Ｓ−、−ＳＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ２ＯＣＨ_２ＣＨ_２−、−ＯＣＨ_２ＣＨ_２Ｏ−、−ＯＣＨ_２Ｏ−、−ＮＨＣＨ_２−、−Ｎ（ＣＨ_３）ＣＨ_２−、−Ｎ^＋（ＣＨ_３）_２ＣＨ_２−、−ＮＨＣＨ_２ＣＨ_２ＣＨ_２−、−Ｎ（ＣＨ_３）ＣＨ_２ＣＨ_２ＣＨ_２−等が挙げられる。好ましくは、−ＣＨ_２−、−ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２−、−ＣＨ_２ＣＨ_２ＣＨ_２ＣＨ_２−、−ＯＣＨ_２ＣＨ_２Ｏ−、−ＯＣＨ_２Ｏ−、−Ｎ（ＣＨ_３）ＣＨ_２ＣＨ_２ＣＨ_２−が挙げられる。
式（ＩＥ）の例として、以下の式に示す化合物

（式中、各記号は上記と同意義である。）等が挙げられる。 In the case where B ¹ is CR ^3a R ^3b and B ² is NR ² , and R ² and R ⁴ together with the adjacent atoms form a heterocyclic ring optionally substituted by Substituent Group D , “Furthermore, the heterocyclic ring may form a bridge” means that the following formula (IE):

(Wherein each symbol is as defined above).
In (IE), "A ⁶ represents a single bond, or a substituted or unsubstituted alkylene which may have an intervening hetero atom" as of "A ⁶ represents a single bond", given by the following Expression (IE '):

The compound shown by these is shown.
In addition, in the formula (IE ′), “A ⁶ may intervene a substituted or unsubstituted hetero atom of a single bond or alkylene which may intervene a substituted or unsubstituted hetero atom” The term "alkylene" embraces linear or branched alkylene having 1 to 6 carbon atoms in which one or two hetero atoms which may be substituted by the above "alkyl" may intervene, for example, _{-CH 2 -, - CH 2 CH} 2 -, - CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 CH 2 -, - CH 2 CH 2 _{CH 2 CH 2 CH 2 CH 2} -, - CH 2 O -, - OCH 2 -, - CH 2 CH 2 O -, - OCH 2 CH 2 -, - CH 2 S -, - SCH 2 -, - CH 2 _{CH2 S -, - SCH 2 CH} 2 -, - C _{2 CH2OCH 2 CH 2 -, -} OCH 2 CH 2 O -, - OCH 2 O -, - NHCH 2 -, - N (CH 3) CH 2 -, - N + (CH 3) 2 CH 2 -, - NHCH _{2 CH 2 CH 2 -, -} N (CH 3) CH 2 CH 2 CH 2 - and the like. _{Preferably, -CH 2 -, - CH 2} CH 2 -, - CH 2 CH 2 CH 2 -, - CH 2 CH 2 CH 2 CH 2 -, - OCH 2 CH 2 O -, - OCH 2 O -, - _{N (CH 3) CH 2 CH} 2 CH 2 - and the like.
As an example of the formula (IE), a compound represented by the following formula

(Wherein each symbol is as defined above) and the like.

  A feature of the present invention is that it also has cap-dependent endonuclease inhibitory activity by converting a polycyclic pyridone compound into a polycyclic pyridazine compound.

  Another feature of the compound according to the present invention is that by introducing a group forming a prodrug, it is efficiently absorbed into the body after administration to a living body (for example, oral administration) and exhibits high efficacy. It is.

One or more of the hydrogen, carbon and / or other atoms of the compounds according to the invention may be replaced by 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. ^{Like 36} Cl, hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine and chlorine are included. The compounds according to the invention also encompass such isotopically substituted compounds. The isotopically substituted compounds are also useful as pharmaceuticals and encompass all radioactive labels of the compounds according to the invention. The present invention also includes a "radiolabeling method" for producing the "radioactive label", and the "radioactive label" is useful as a research and / or diagnostic tool in metabolism pharmacokinetic study, binding assay. It is.

Radioactive labels of the compounds according to the invention can be prepared by methods known in the art. For example, the tritium labeled compound of the compound according to the present invention can be prepared by introducing tritium into a specific compound according to the present invention by a catalytic dehalogenation reaction using tritium. This method includes reacting tritium gas with a suitably halogen-substituted precursor of the compound according to the present invention in the presence or absence of a base in the presence of a suitable catalyst such as Pd / C. Do. 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 according to the present invention include the compound according to the present invention, an alkali metal (eg, lithium, sodium, potassium etc.), an alkaline earth metal (eg calcium, barium etc.), Magnesium, transition metals (eg, zinc, iron etc.), ammonia, organic bases (eg, trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethylenediamine, pyridine, picoline, quinoline etc.) and amino acids Or inorganic acids (eg, hydrochloric acid, sulfuric acid, nitric acid, carbonic acid, hydrobromic acid, phosphoric acid, hydroiodic acid etc.), and organic acids (eg, formic acid, acetic acid, propionic acid, trifluoroacetic acid, citric acid) Acid, lactic acid, tartaric acid, oxalic acid, maleic acid, Le acid, mandelic acid, glutaric acid, malic acid, benzoic acid, phthalic acid, ascorbic acid, benzenesulfonic acid, p- toluenesulfonic acid, methanesulfonic acid, and salts with 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 methods which are commonly performed.

  The compound represented by the formula (I) of the present invention or a pharmaceutically acceptable salt thereof may form a solvate (eg, hydrate etc.), co-crystal and / or crystal polymorph, and 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 molecule etc.) with respect to the compound represented by the formula (I). When the compound represented by the formula (I) or a pharmaceutically acceptable salt thereof is allowed to stand in the air, it absorbs water, and may adsorb adsorbed water or may form a hydrate. In addition, the compound represented by formula (I) or a pharmaceutically acceptable salt thereof may be recrystallized to form a crystalline polymorph. "Co-crystal" means that the compound or salt of Formula (I) and the counter molecule are present in the same crystal lattice, and may be formed with any number of counter molecules.

で示される化合物における、Ｐ、Ｂ^１、Ｂ^２、Ｒ^１、Ｒ^２、Ｒ^３ａ、Ｒ^３ｂ、Ｒ^４の好ましい態様を以下に示す。下記の可能な組合せの化合物が好ましい。
Ｐは水素またはプロドラッグを形成する基が挙げられる。
Ｐの好ましい態様としては、水素が挙げられる。
Ｐの別の好ましい態様としては、プロドラッグを形成する基が挙げられる。 The group forming a prodrug is preferably a group which is converted to an OH group by the action of a drug-metabolizing enzyme, a hydrolase, a gastric acid, and / or an enteric bacterium after administration to a living body (eg, oral administration).
Particularly preferred embodiments of the compound of the present invention are shown below.
Formula (I):

Preferred embodiments of P, B ¹ , B ² , R ¹ , R ² , R ^3a , R ^3b and R ^{4 in} the compounds represented by the following are shown below. The following possible combinations of compounds are preferred:
P is hydrogen or a group forming a prodrug.
A preferred embodiment of P includes hydrogen.
Another preferred embodiment of P includes groups that form a prodrug.

More preferred embodiments of groups forming a prodrug include groups selected from the following formulas a) to ac).
^{a) -C (= O) -P} R0,
^{b) -C (= O) -P} R1,
c) -C (= O) -L- ^PR1 ,
d) -C (= O) -L-O-P ^R1 ,
e) -C (= O) -L-O-L-O-P ^R1 ,
f) -C (= O) -L-O-C (= O) -P ^R1 ,
g) -C (= O) -O- ^PR2 ,
h) -C (= O) -N (-K) ( ^PR2 ),
i) -C (= O) -O-L-O- ^PR2 ,
j) -C ( ^PR3 ) _2- O- ^PR4 ;
k) -C ( ^PR3 ) _2- O-L-O- ^PR4 ,
_{^{l) -C (P R3) 2}} -O-C (= O) -P R4,
m) -C ( ^PR3 ) _2- O-C (= O) -OP- ^R4 ,
_{^{n) -C (P R3) 2}} -O-C (= O) -N (-K) -P R4,
o) -C ( ^PR3 ) _2- O-C (= O) -O-L-O- ^PR4 ,
p) -C ( ^PR3 ) _2- OC (= O) -OLN ( ^PR4 ) ₂ ,
q) -C ( ^PR3 ) _2- OC (= O) -N (-K) -LO- ^PR4 ;
r) -C ( ^PR3 ) _2- OC (= O) -N (-K) -L-N ( ^PR4 ) ₂ ,
s) -C ( ^PR3 ) _2- O-C (= O) -O-L-O-L-O- ^PR4 ,
_{^{t) -C (P R3) 2}} -O-C (= O) -O-L-N (-K) -C (= O) -P R4,
u) -C ( ^PR3 ) ₂ -OP (= O) ( ^-PR5 ) ₂ ,
_{^{v) -C (P R3) 2}} -P R6,
w)-C (= N ⁺ ( ^PR7 ) ₂ ) (-N ( ^PR7 ) ₂ ),
x) -C ( ^PR3 ) _2- C ( ^PR3 ) _2- C (= O) -O- ^PR2 ,
y) -C ( ^PR3 ) _2- N (-K) -C (= O) -O- ^PR2 ,
z)-P (= O) ( ^-PR8 ) ( ^-PR9 ),
^{_{aa) -S (= O) 2}} -P R10,
^{ab) -P R11,} and _{^{ac) -C (P R3) 2}} -C (P R3) 2 -O-P R2,
Wherein L is linear or branched alkylene, or linear or branched alkenylene,
K is hydrogen or alkyl optionally substituted with substituent group A,
P ^R0 is an alkyl which may be substituted with the substituent group A or an alkenyl which may be substituted with the substituent group A,
P ^{R 1} represents a carbocyclic group which may be substituted with substituent group A, a heterocyclic group which may be substituted with substituent group A, an alkylamino which may be substituted with substituent group A, Or alkylsulfanyl optionally substituted with substituent group A,
P ^{R 2} is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, heterocyclic alkyl which may be substituted by substituent group A, or trialkylsilyl;
And each P ^R3 is independently hydrogen or alkyl,
P ^{R 4} each independently represents an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a complex which may be substituted with the substituent group A Cyclic group, alkylamino which may be substituted with substituent group A, carbocyclic alkyl which may be substituted with substituent group A, heterocyclic alkyl which may be substituted with substituent group A, or tri It is alkylsilyl and
And P ^R5 is independently hydroxy or benzyloxy,
P ^R6 is a carbocyclic group which may be substituted with the substituent group A or a heterocyclic group which may be substituted with the substituent group A,
Each P ^R7 is independently an alkyl which may be substituted with Substituent Group A,
^{PR 8} is alkyloxy optionally substituted with substituent group A,
^{PR 9} is alkyloxy optionally substituted with substituent group A, alkylamino optionally substituted with substituent group A, carbocyclic ring oxy optionally substituted with substituent group A, substituent group A heterocyclic oxy which may be substituted by A, a carbocyclic amino which may be substituted by a substituent group A, or a heterocyclic amino which may be substituted by a substituent group A,
P ^R8 and P ^R9 may be taken together with the adjacent phosphorus atom to form a heterocyclic ring which may be substituted with Substituent Group A,
P ^R10 is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, or heterocyclic alkyl which may be substituted by substituent group A,
P ^{R 11} represents an alkyl which may be substituted with the substituent group A, an alkenyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a substituent group A heterocyclic group optionally substituted by A.
Substituent group A: oxo, alkyl, hydroxyalkyl, amino, alkylamino, carbocyclic group, heterocyclic group, carbocyclic alkyl, alkylcarbonyl, halogen, hydroxy, carboxy, alkylcarbonylamino, alkylcarbonylaminoalkyl, alkyl Carbonyloxy, alkyloxycarbonyl, alkyloxycarbonylalkyl, alkyloxycarbonyloxy, alkylaminocarbonyloxy, alkylaminoalkyl, alkyloxy, cyano, nitro, azide, alkylsulfonyl, trialkylsilyl, and phospho).

The following groups may be mentioned as further preferred embodiments of the groups forming a prodrug.
^{a) -C (= O) -P} R0,
^{b) -C (= O) -P} R1,
g) -C (= O) -O- ^PR2 ,
h) -C (= O) -N (-K) ( ^PR2 ),
i) -C (= O) -O-L-O- ^PR2 ,
_{^{l) -C (P R3) 2}} -O-C (= O) -P R4,
m) -C ( ^PR3 ) _2- O-C (= O) -OP- ^R4 ,
o) -C ( ^PR3 ) _2- O-C (= O) -O-L-O- ^PR4 ,
_{^{v) -C (P R3) 2}} -P R6 ( excluding benzyl group),
x) -C ( ^PR3 ) _2- C ( ^PR3 ) _2- C (= O) -O- ^PR2 ,
y) -C ( ^PR3 ) _2- N (-K) -C (= O) -O- ^PR2 , and z) -P (= O) ( ^-PR8 ) ( ^-PR9 ),
Wherein L is a linear or branched alkylene,
K is hydrogen or alkyl optionally substituted with substituent group A,
P ^R0 is alkyl ^optionally substituted with Substituent Group A,
P ^R1 is a carbocyclic group which may be substituted with substituent group A or a heterocyclic group which may be substituted with substituent group A,
P ^{R 2} is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, or heterocyclic alkyl which may be substituted by substituent group A,
And each P ^R3 is independently hydrogen or alkyl,
P ^{R 4} represents an alkyl which may be substituted with substituent group A, a carbocyclic group which may be substituted with substituent group A, or a heterocyclic group which may be substituted with substituent group A Yes,
P ^R6 is a carbocyclic group which may be substituted with the substituent group A or a heterocyclic group which may be substituted with the substituent group A,
^{PR 8} is alkyloxy optionally substituted with substituent group A,
^{PR 9} is alkyloxy optionally substituted with substituent group A, alkylamino optionally substituted with substituent group A, carbocyclic ring oxy optionally substituted with substituent group A, substituent group Heterocyclic ring optionally substituted with A, carbocyclic amino optionally substituted with substituent group A, or heterocyclic amino optionally substituted with substituent group A, and ^{PR 8} and P ^{R 9} may be taken together with the adjacent phosphorus atom to form a heterocyclic ring which may be substituted with Substituent Group A.
Substituent group A: oxo, alkyl, alkylamino, carbocyclic group, heterocyclic group, alkylcarbonyl, halogen, hydroxy, alkylcarbonylamino, alkylcarbonyloxy, alkyloxycarbonyl, alkyloxycarbonylalkyl, alkylaminocarbonyloxy (Alkyloxy, nitro, azide, alkylsulfonyl and trialkylsilyl).

Other embodiments of preferred substituents of groups forming a prodrug include the following groups.

B ¹ is NR ² , and B ² is CR ^3a R ^3b .
B ¹ includes CR ^3a R ^3b , and B ² includes NR ² .
Preferred embodiments of B ¹ and B ² include B ¹ is NR ² and B ² is CR ^3a R ^3b .

R ¹ is hydrogen, halogen, hydroxy, carboxy, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, alkyl optionally substituted with substituent group C And oxy, an alkylcarbonyl which may be substituted with substituent group C, an alkyloxycarbonyl which may be substituted with substituent group C, or -Z-N (R ^A1 ) (R ^A2 ).
Preferred embodiments of R ¹ include hydrogen, carboxy, or -Z-N (R ^A1 ) (R ^A2 ).

（式中、Ｒ^Ｅ6は、置換基群Ｃから選ばれ、ｍは０または１以上の整数であり、但し、ｍ個のＲ^Ｅ6は、置換基群Ｃから選ばれる同一または異なっていてもよい基である）。
Ｒ^２のさらに好ましい態様としては、以下の基が挙げられる。

Ｒ^２の別の態様としては、以下の基が挙げられる。

（式中、Ｒ^２Ａ、Ｒ^２Ｂ、Ｒ^２ＣおよびＲ^２Ｄは、それぞれ独立して、水素またはフッ素原子であり、Ｒ^２Ａ、Ｒ^２Ｂ、Ｒ^２ＣおよびＲ^２Ｄのフッ素原子の数は、１または２である）。
Ｒ^２のさらに別の態様としては、以下の基が挙げられる。

When B ¹ is NR ² and B ² is CR ^3a R ^3b ,
R ² is hydrogen, carboxy, cyano, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, alkynyl optionally substituted with substituent group C, substituted Alkyl carbonyl which may be substituted by group C, alkyloxycarbonyl which may be substituted by substituent C, carbocyclic group which may be substituted by substituent C, substituted by substituent C Carbocyclic ring alkyl which may be substituted, carbocyclic ring oxyalkyl optionally substituted by substituent group C, carbocyclic ring carbonyl optionally substituted by substituent group C, even if substituted by substituent group C Good carbocyclic ring oxycarbonyl, heterocyclic group which may be substituted with substituent group C, heterocyclic alkyl which may be substituted with substituent group C, heterocyclic ring which may be substituted with substituent group C Oxial Kill, heterocyclic carbonyl optionally substituted with substituent group C, heterocyclic oxycarbonyl optionally substituted with substituent group C,
-Y-S-R ^B1 ,
-Z-S (= O) -R B2,
-Z-SO _2- R ^B3 ,
-C (= O) -C (= O) -R B4,
-C (= O) -N (R ^B5 ) (R ^B6 ),
-Z-C ( ^RB7 ) ( ^RB8 ) ( ^RB9 )
-Z-N ( ^RB11 ) -C (= O) -O- ^RB12 or -Z-N ( ^RB13 ) -C (= O) ^-RB14
Can be mentioned.
Preferred embodiments of R ² include the following groups.

(Wherein, R ^E6 is selected from Substituent Group C, m is an integer of 0 or 1 or more, provided that m R ^E6 may be the same or different selected from Substituent Group C) Group).
The following groups are mentioned as a further preferable aspect of R ² .

Another aspect of R ² includes the following groups.

(Wherein, R ^2A , R ^2B , R ^2C and R ^2D are each independently hydrogen or a fluorine atom, and the number of fluorine atoms of R ^2A , R ^2B , R ^2C and R ^2D is 1 or 2) Is).
As still another aspect of R ² , the following groups may be mentioned.

When B ¹ is NR ² and B ² is CR ^3a R ^3b ,
When R ^{3a and} R ^3b , and R ^3b and R ⁴ respectively form a ring together with adjacent atoms, R ^3a is hydrogen, R ^3b is hydrogen, R ⁴ is hydrogen, or Substituent group C Alkyl which may be substituted is mentioned.
When R ^3b and R ⁴ are taken together with adjacent atoms to form a heterocyclic ring which may be substituted by Substituent Group D, R ^3a includes hydrogen.

（式中、Ｒ^Ｅ6は、置換基群Ｃから選ばれ、ｍは０または１以上の整数であり、但し、ｍ個のＲ^Ｅ6は、置換基群Ｃから選ばれる同一または異なっていてもよい基である）。
Ｒ^３ｂのさらに好ましい態様としては、以下の基が挙げられる。

Ｒ^３ｂの別の態様としては、以下の基が挙げられる。

（式中、Ｒ^２Ａ、Ｒ^２Ｂ、Ｒ^２ＣおよびＲ^２Ｄは、それぞれ独立して、水素またはフッ素原子であり、Ｒ^２Ａ、Ｒ^２Ｂ、Ｒ^２ＣおよびＲ^２Ｄのフッ素原子の数は、１または２である）。
Ｒ^３ｂのさらに別の態様としては、以下の基が挙げられる。

When B ¹ is CR ^3a R ^3b and B ² is NR ² ,
R ^3b is hydrogen, carboxy, cyano, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, alkynyl optionally substituted with substituent group C, substituted Alkyl carbonyl which may be substituted by group C, alkyloxycarbonyl which may be substituted by substituent C, carbocyclic group which may be substituted by substituent C, substituted by substituent C Carbocyclic ring alkyl which may be substituted, carbocyclic ring oxyalkyl optionally substituted by substituent group C, carbocyclic ring carbonyl optionally substituted by substituent group C, even if substituted by substituent group C Good carbocyclic ring oxycarbonyl, heterocyclic group which may be substituted with substituent group C, heterocyclic alkyl which may be substituted with substituent group C, heterocyclic ring which may be substituted with substituent group C Oxia Alkyl, heterocyclic carbonyl optionally substituted with substituent group C, heterocyclic oxycarbonyl optionally substituted with substituent group C,
-Y-S-R ^B1 ,
-Z-S (= O) -R B2,
-Z-SO _2- R ^B3 ,
-C (= O) -C (= O) -R B4,
-C (= O) -N (R ^B5 ) (R ^B6 ),
-Z-C ( ^RB7 ) ( ^RB8 ) ( ^RB9 )
-Z-N ( ^RB11 ) -C (= O) -O- ^RB12 or -Z-N ( ^RB13 ) -C (= O) ^-RB14
Can be mentioned.
Preferred embodiments of R ^3b include the following groups.

(Wherein, R ^E6 is selected from Substituent Group C, m is an integer of 0 or 1 or more, provided that m R ^E6 may be the same or different selected from Substituent Group C) Group).
More preferable embodiments of R ^3b include the following groups.

Another aspect of R ^3b includes the following groups.

(Wherein, R ^2A , R ^2B , R ^2C and R ^2D are each independently hydrogen or a fluorine atom, and the number of fluorine atoms of R ^2A , R ^2B , R ^2C and R ^2D is 1 or 2) Is).
As still another aspect of R ^3b , the following groups may be mentioned.

When B ¹ is CR ^3a R ^3b and B ² is NR ² ,
When R ² and R ⁴ together with the adjacent atoms do not form a heterocyclic ring optionally substituted with substituent group D, R ² is hydrogen or an alkyl optionally substituted with substituent group C And R ^3a is hydrogen, R ⁴ is hydrogen or alkyl optionally substituted with substituent group C.
When R ² and R ⁴ are taken together with adjacent atoms to form a heterocyclic ring which may be substituted by Substituent Group D, R ^3a includes hydrogen.

で示される部分構造が、以下のいずれかの式で示される化合物が好ましい。

The partial structure represented by is preferably a compound represented by any one of the following formulas.

(Method for producing the compound of the present invention)
The general methods for preparing the compounds of the present invention are exemplified below. In addition, extraction, purification, and the like may be carried out by ordinary organic chemistry experiments.
The synthesis of the compounds of the present invention can be carried out with reference to techniques known in the art.

As starting compounds, commercially available compounds, those described herein, those described in the documents cited herein, and other known compounds can be used.
When it is desired to obtain a salt of the compound of the present invention, when the compound of the present invention is obtained in the form of a salt, it may be purified as it is, or when it is obtained in the free form, it may be dissolved in a suitable organic solvent Alternatively, it may be suspended and an acid or a base may be added to form a salt by a conventional method.
Further, the compound of the present invention and its pharmaceutically acceptable salt may exist in the form of water or an adduct (hydrate or solvate) with various solvents, and these adducts are also included in the present invention. Is included.

In the general synthesis methods and Reference Examples, Examples, and Intermediate Synthesis Examples, the meanings of the abbreviations are as follows.
Alloc: allyloxycarbonyl DEAD: diethylazodicarboxylate DIAD: diisopropyl dicarboxylate DMA: N, N-dimethylacetamide DMF: N, N-dimethylformamide DPPA: diphenyl phosphate azido NMP: N-methylpyrrolidone OBn: benzyloxy THF: tetrahydrofuran T3P: propylphosphonic anhydride

（式中、Ｐ^１、Ｐ^２はカルボキシ保護基であり、Ｐ^３はヒドロキシ保護基およびアミノ保護基であり、Ｐ^４はアミノ保護基であり、その他の記号は前記と同義である。）
第一工程
公知の方法で調製できる化合物ａ１に、アセトニトリル、ＤＭＦ、ＤＭＡ、ＴＨＦ等の溶媒の存在下、トリエチルアミン、ジイソプロピルエチルアミン、Ｎ−メチルモルホリン等の３級アミンを加え、４−アセトアミドベンゼンスルホニルアジド、ｐ‐トルエンスルホニルアジド等のスルホニルアジドを加え、−１０℃〜６０℃、好ましくは０℃〜２５℃にて０．１時間〜６時間、好ましくは０．５時間〜３時間反応させることにより、化合物ａ２を得ることができる。
第二工程
化合物ａ２に、ＤＭＦ、ＤＭＡ、ＮＭＰ、ＴＨＦ等の溶媒の存在下、炭酸カリウム、炭酸ナトリウム等の塩基を加え、Ｏ−（２，４−ジニトロフェニル）ヒドロキシルアミン等のアミノ化試薬を加え、１０℃〜６０℃、好ましくは２０℃〜４０℃にて０．１時間〜２４時間、好ましくは１時間〜１２時間反応させることにより、化合物ａ３を得ることができる。
第三工程
化合物ａ３に、ＴＨＦ、ジオキサン、トルエン、ジクロロメタン等の溶媒の存在下、低級アルキルアルコールを加え、トリフェニルホスフィンを加え、ＤＥＡＤ、ＤＩＡＤ等の光延試薬を加え、０℃〜８０℃、好ましくは１０℃〜２０℃にて０．１時間〜１２時間、好ましくは０．５時間〜３時間反応させることにより、化合物ａ４を得ることができる。
第四工程
化合物ａ４に、酢酸等の溶媒の存在下、化合物ａ５を加え、２０℃〜１５０℃、好ましくは６０℃〜１２０℃にて０．５時間〜２４時間、好ましくは１時間〜６時間反応させることにより、化合物ａ６を得ることができる。
第五工程
化合物ａ６を、アミノ保護基の公知の一般的な脱保護反応に付すことにより、化合物ａ７を得ることができる。
第六工程
化合物ａ７に、酢酸エチル、テトラヒドロフラン、ジオキサン、トルエン等の溶媒の存在下、化合物ａ８を加え、Ｔ３Ｐを加え、メタンスルホン酸等の酸を加え、２０℃〜１２０℃、好ましくは、５０℃〜１００℃にて、０．１時間〜１２時間、好ましくは０．５時間〜３時間反応させることにより、化合物ａ９を得ることができる。
第七工程
化合物a９を公知の一般的なカルボキシル基の脱保護反応に付すことにより、化合物a１０を得ることができる。
第八工程
化合物ａ１０に、ＤＭＦ、トルエン、ジオキサン、ＴＨＦ等の溶媒の存在下、トリエチルアミン、ジイソプロピルエチルアミン、Ｎ−メチルモルホリン等の３級アミンを加え、ＤＰＰＡを加え、４０℃〜１２０℃、好ましくは、６０℃〜１００℃にて０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させ、０℃〜３０℃、好ましくは、０℃〜１０℃に冷却後、水酸化ナトリウム水溶液を加え、同温度で０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させることにより、化合物ａ１１を得ることができる。
第九工程
化合物a１１に、THF、ジオキサン等の溶媒の存在下、次亜リン酸水溶液を加え、亜硝酸ナトリウム、亜硝酸カリウム等の亜硝酸塩を加え、０℃〜５０℃、好ましくは０℃〜１０℃にて、０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させることにより、化合物a１２を得ることができる。
第十工程
化合物a１２を公知の一般的なヒドロキシル基の脱保護反応に付すことにより、化合物a１３を得ることができる。 (Method 1)

(Wherein P ¹ and P ² are carboxy protecting groups, P ³ is a hydroxy protecting group and an amino protecting group, P ⁴ is an amino protecting group, and the other symbols are as defined above).
First Step To compound a1 which can be prepared by a known method, a tertiary amine such as triethylamine, diisopropylethylamine, N-methylmorpholine, etc. is added in the presence of a solvent such as acetonitrile, DMF, DMA, THF etc. By adding a sulfonyl azide such as p-toluenesulfonyl azide and the like, and reacting at −10 ° C. to 60 ° C., preferably at 0 ° C. to 25 ° C. for 0.1 hour to 6 hours, preferably 0.5 hour to 3 hours , Compound a2 can be obtained.
Second Step A compound such as potassium carbonate, sodium carbonate or the like is added to compound a2 in the presence of a solvent such as DMF, DMA, NMP, THF or the like to give an amination reagent such as O- (2,4-dinitrophenyl) hydroxylamine In addition, compound a3 can be obtained by reacting at 10 ° C. to 60 ° C., preferably at 20 ° C. to 40 ° C., for 0.1 hour to 24 hours, preferably 1 hour to 12 hours.
Third Step To compound a3 is added a lower alkyl alcohol in the presence of a solvent such as THF, dioxane, toluene or dichloromethane, triphenylphosphine is added, a Mitsunobu reagent such as DEAD or DIAD is added, and 0 ° C to 80 ° C is preferable. The compound a4 can be obtained by reacting at 10 ° C. to 20 ° C. for 0.1 hour to 12 hours, preferably 0.5 hour to 3 hours.
Fourth Step To compound a4 is added compound a5 in the presence of a solvent such as acetic acid, and the temperature is 20 ° C. to 150 ° C., preferably 60 ° C. to 120 ° C. for 0.5 to 24 hours, preferably 1 to 6 hours Compound a6 can be obtained by reaction.
Fifth Step A compound a7 can be obtained by subjecting the compound a6 to a known general deprotection reaction of an amino protecting group.
Sixth Step A compound a8 is added to a compound a7 in the presence of a solvent such as ethyl acetate, tetrahydrofuran, dioxane, toluene, etc., T3P is added, an acid such as methanesulfonic acid is added, and 20 ° C to 120 ° C, preferably 50 The compound a9 can be obtained by reacting at 100 ° C. to 100 ° C. for 0.1 hour to 12 hours, preferably 0.5 hours to 3 hours.
Seventh Step A compound a10 can be obtained by subjecting the compound a9 to a known general carboxyl group deprotecting reaction.
Eighth step To compound a10 is added a tertiary amine such as triethylamine, diisopropylethylamine, N-methylmorpholine or the like in the presence of a solvent such as DMF, toluene, dioxane, THF or the like, DPPA is added, and 40 ° C to 120 ° C, preferably , After reacting at 60 ° C. to 100 ° C. for 0.1 hour to 6 hours, preferably 0.5 hour to 3 hours, and cooling to 0 ° C. to 30 ° C., preferably 0 ° C. to 10 ° C., sodium hydroxide An aqueous solution is added, and reaction is carried out at the same temperature for 0.1 hour to 6 hours, preferably 0.5 hour to 3 hours, to obtain compound a11.
Ninth step An aqueous solution of hypophosphorous acid is added to compound a11 in the presence of a solvent such as THF or dioxane, a nitrite such as sodium nitrite or potassium nitrite is added, and the temperature is 0 ° C to 50 ° C, preferably 0 ° C to 10 The compound a12 can be obtained by reacting at 0 C for 0.1 hour to 6 hours, preferably for 0.5 hour to 3 hours.
Tenth Step A compound a13 can be obtained by subjecting the compound a12 to a known general hydroxyl group deprotecting reaction.

（式中、各記号は前記と同義である。）
第一工程
化合物ａ４を公知の一般的なカルボキシル基の脱保護反応に付すことにより、化合物ｂ１を得ることができる。
第二工程
化合物ｂ１に、水、メタノール、エタノール等の溶媒の存在下、化合物ｂ２を加え、０℃〜１５０℃、好ましくは、２０℃〜１２０℃にて、１時間〜２４時間、好ましくは２時間〜６時間反応させることにより、化合物ｂ３を得ることができる。
第三工程
化合物ｂ３に、ＤＭＦ、ＮＭＰ、ＤＭＡ等の溶媒の存在下、化合物ｂ４および酢酸を加え、６０℃〜１５０℃、好ましくは８０℃〜１２０℃にて０．１時間〜２４時間、好ましくは１時間〜１２時間反応させることにより、化合物ｂ５を得ることができる。
第四工程
化合物ｂ５に、酢酸エチル、ＴＨＦ、ジオキサン、トルエン等の溶媒の存在下、化合物ａ８を加え、Ｔ３Ｐを加え、２０℃〜１２０℃、好ましくは、５０℃〜１００℃にて、０．１時間〜１２時間、好ましくは０．５時間〜３時間反応させることにより、化合物ｂ６を得ることができる。
第五工程
化合物ｂ６に、ＤＭＦ、トルエン、ジオキサン、ＴＨＦ等の溶媒の存在下、トリエチルアミン、ジイソプロピルエチルアミン、Ｎ−メチルモルホリン等の３級アミンを加え、ＤＰＰＡを加え、４０℃〜１２０℃、好ましくは、６０℃〜１００℃にて０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させ、０℃〜３０℃、好ましくは、０℃〜１０℃に冷却後、水酸化ナトリウム水溶液を加え、同温度で０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させることにより、化合物ｂ７を得ることができる。
第六工程
化合物ｂ７に、ＴＨＦ、ジオキサン等の溶媒の存在下、次亜リン酸水溶液を加え、亜硝酸ナトリウム、亜硝酸カリウム等の亜硝酸塩を加え、０℃〜５０℃、好ましくは０℃〜１０℃にて、０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させることにより、化合物ｂ８を得ることができる。
第七工程
化合物ｂ８を公知の一般的なヒドロキシル基の脱保護反応に付すことにより、化合物ｂ９を得ることができる。 (Method 2)

(Wherein each symbol is as defined above)
First Step A compound b1 can be obtained by subjecting the compound a4 to a known general carboxyl group deprotecting reaction.
Second Step: Compound b2 is added to compound b1 in the presence of a solvent such as water, methanol, ethanol etc., and the mixture is heated at 0 ° C to 150 ° C, preferably 20 ° C to 120 ° C, for 1 hour to 24 hours, preferably 2 Compound b3 can be obtained by reacting for 6 hours.
Third step Compound b4 and acetic acid are added to compound b3 in the presence of a solvent such as DMF, NMP, DMA, etc., and the temperature is 60 ° C. to 150 ° C., preferably 80 ° C. to 120 ° C. for 0.1 hour to 24 hours, preferably Can be reacted for 1 hour to 12 hours to give compound b5.
Fourth Step To compound b5, compound a8 is added in the presence of a solvent such as ethyl acetate, THF, dioxane, toluene and the like, T3P is added, and at 0 ° C to 120 ° C, preferably 50 ° C to 100 ° C, 0. The compound b6 can be obtained by reacting for 1 hour to 12 hours, preferably for 0.5 hours to 3 hours.
Fifth Step To compound b6 is added a tertiary amine such as triethylamine, diisopropylethylamine, N-methylmorpholine or the like in the presence of a solvent such as DMF, toluene, dioxane, THF or the like, DPPA is added, and 40 ° C to 120 ° C, preferably , After reacting at 60 ° C. to 100 ° C. for 0.1 hour to 6 hours, preferably 0.5 hour to 3 hours, and cooling to 0 ° C. to 30 ° C., preferably 0 ° C. to 10 ° C., sodium hydroxide An aqueous solution is added, and reaction is carried out at the same temperature for 0.1 hour to 6 hours, preferably 0.5 hour to 3 hours, to give compound b7.
Sixth step An aqueous solution of hypophosphorous acid is added to compound b7 in the presence of a solvent such as THF or dioxane, a nitrite such as sodium nitrite or potassium nitrite is added, and the temperature is 0 ° C to 50 ° C, preferably 0 ° C to 10 ° C. The compound b8 can be obtained by reacting at 0 C for 0.1 hour to 6 hours, preferably for 0.5 hour to 3 hours.
Seventh Step A compound b9 can be obtained by subjecting the compound b8 to a known general hydroxyl group deprotecting reaction.

（式中、各記号は前記と同義である。）
第一工程
化合物ａ２に、ＴＨＦ、ジオキサン、トルエン、ジクロロメタン等の溶媒の存在下、低級アルキルアルコールを加え、トリフェニルホスフィンを加え、ＤＥＡＤ、ＤＩＡＤ等の光延試薬を加え、０℃〜８０℃、好ましくは１０℃〜２０℃にて０．１時間〜１２時間、好ましくは０．５時間〜３時間反応させることにより、化合物ｃ１を得ることができる。
第二工程
化合物ｃ１を公知の一般的なカルボキシル基の脱保護反応に付すことにより、化合物ｃ２を得ることができる。
第三工程
化合物ｃ２に、ＤＭＦ、トルエン、ジオキサン、ＴＨＦ等の溶媒の存在下、トリエチルアミン、ジイソプロピルエチルアミン、Ｎ−メチルモルホリン等の３級アミンを加え、ＤＰＰＡを加え、４０℃〜１２０℃、好ましくは、６０℃〜１００℃にて０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させ、０℃〜３０℃、好ましくは、０℃〜１０℃に冷却後、水酸化ナトリウム水溶液を加え、同温度で０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させることにより、化合物ｃ３を得ることができる。
第四工程
化合物ｃ３に、ＴＨＦ、ジオキサン等の溶媒の存在下、次亜リン酸水溶液を加え、亜硝酸ナトリウム、亜硝酸カリウム等の亜硝酸塩を加え、０℃〜５０℃、好ましくは０℃〜１０℃にて、０．１時間〜６時間、好ましくは、０．５時間〜３時間反応させることにより、化合物ｃ４を得ることができる。
第五工程
化合物ｃ４を公知の一般的なカルボキシル基の脱保護反応に付すことにより、化合物ｃ５を得ることができる。
第六工程
化合物ｃ５に、ジクロロメタン、クロロホルム、ＴＨＦ等の溶媒の存在下、1-クロロ-N,N,2- トリメチルプロペニルアミン等の縮合剤を加え、０．１時間〜３時間、好ましくは０．５時間〜２時間反応させ、市販または公知の方法により調製できる化合物ｃ６および、トリエチルアミン、Ｎ−メチルモルホリン、ピリジン等の３級アミンを加え、１０℃〜６０℃、好ましくは２０℃〜４０℃にて０．１時間〜２４時間、好ましくは１時間〜１２時間反応させることにより、化合物ｃ７を得ることができる。
第七工程
化合物ｃ７を、アミノ保護基の公知の一般的な脱保護反応に付すことにより、化合物ｃ８を得ることができる。
第八工程
化合物ｃ８を、ヒドロキシおよびアミノ保護基の公知の一般的な脱保護反応に付すことにより、化合物ｃ９を得ることができる。
第九工程
化合物ｃ９に、トルエン、ＤＭＦ、ＤＭＡ、ＮＭＰ等の溶媒の存在下、市販または、公知の方法で調製できる化合物ｃ１０、トリエチルアミン、ジイソプロピルエチルアミン、Ｎ−メチルモルホリン等の３級アミンおよび酢酸を加え、６０℃〜１２０℃、好ましくは８０℃〜１００℃にて０．１時間〜２４時間、好ましくは１時間〜１２時間反応させることにより、化合物ｃ１１を得ることができる。 (Method 3)

(Wherein each symbol is as defined above)
First Step To compound a2 is added lower alkyl alcohol in the presence of a solvent such as THF, dioxane, toluene, dichloromethane and the like, triphenylphosphine is added, Mitsunobu reagent such as DEAD and DIAD is added, 0 ° C-80 ° C, preferably The compound c1 can be obtained by reacting at 10 ° C. to 20 ° C. for 0.1 hour to 12 hours, preferably 0.5 hour to 3 hours.
Second Step A compound c2 can be obtained by subjecting the compound c1 to a known general carboxyl group deprotecting reaction.
Third Step To compound c2 is added a tertiary amine such as triethylamine, diisopropylethylamine, N-methylmorpholine or the like in the presence of a solvent such as DMF, toluene, dioxane, THF or the like, DPPA is added, and 40 ° C to 120 ° C, preferably , After reacting at 60 ° C. to 100 ° C. for 0.1 hour to 6 hours, preferably 0.5 hour to 3 hours, and cooling to 0 ° C. to 30 ° C., preferably 0 ° C. to 10 ° C., sodium hydroxide An aqueous solution is added and compound c3 can be obtained by reacting at the same temperature for 0.1 hour to 6 hours, preferably for 0.5 hour to 3 hours.
Fourth step To a compound c3 is added an aqueous solution of hypophosphorous acid in the presence of a solvent such as THF or dioxane, and a nitrite such as sodium nitrite or potassium nitrite is added thereto, and the temperature is 0 ° C to 50 ° C, preferably 0 ° C to 10 ° C. The compound c4 can be obtained by reacting at 0 C for 0.1 hour to 6 hours, preferably for 0.5 hour to 3 hours.
Fifth Step A compound c5 can be obtained by subjecting the compound c4 to a known general carboxyl group deprotecting reaction.
Sixth Step A compound c5 is added with a condensing agent such as 1-chloro-N, N, 2-trimethylpropenylamine in the presence of a solvent such as dichloromethane, chloroform, THF or the like, for 0.1 hour to 3 hours, preferably 0 .5 hours to 2 hours of reaction, compound c6 which can be prepared by a commercially available method or a known method, and a tertiary amine such as triethylamine, N-methylmorpholine, pyridine and the like are added, 10 to 60.degree. The compound c7 can be obtained by reacting for 0.1 hour to 24 hours, preferably 1 hour to 12 hours.
Seventh Step A compound c8 can be obtained by subjecting the compound c7 to a known general deprotection reaction of an amino protecting group.
Eighth Step Compound c9 can be obtained by subjecting compound c8 to known general deprotection reaction of hydroxy and amino protecting groups.
Step 9 Compound c9 is compound c10 that can be prepared by a commercially available method or a known method in the presence of a solvent such as toluene, DMF, DMA, NMP, etc., a tertiary amine such as triethylamine, diisopropylethylamine, N-methylmorpholine, etc. In addition, compound c11 can be obtained by reacting at 60 ° C. to 120 ° C., preferably 80 ° C. to 100 ° C., for 0.1 hour to 24 hours, preferably 1 hour to 12 hours.

  The compounds of the present invention have cap-dependent endonuclease inhibitory activity. Accordingly, the compounds of the present invention are useful as therapeutic and / or prophylactic agents for influenza.

  The compounds of the present invention are useful for influenza virus induced conditions and / or diseases. For example, cold-like symptoms accompanied by fever, chills, headache, muscle pain, general fatigue, etc., gastrointestinal symptoms such as sore throat, nasal discharge, nasal congestion, airway inflammation symptoms such as cough, sputum, abdominal pain, vomiting, diarrhea, etc. It is effective in the treatment and / or prevention of complications associated with secondary infections such as acute encephalopathy and pneumonia, and symptom improvement.

The compounds of the present invention have not only cap-dependent endonuclease inhibitory activity but also utility as pharmaceuticals, and have any or all of the following excellent features.
a) The inhibitory effect on CYP enzymes (eg, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4, etc.) is weak.
b) show good pharmacokinetics such as high bioavailability, moderate clearance and the like.
c) metabolic stability is high.
d) It shows no irreversible inhibitory effect on CYP enzymes (eg, CYP3A4) within the concentration range of measurement conditions described herein.
e) not mutagenic.
f) low cardiovascular risk.
g) show high solubility.
h) not phototoxic.

When the compound of the present invention is administered to humans for the treatment of the above-mentioned diseases, it can be orally administered as a powder, granules, tablets, capsules, pills, solutions and the like, or injections, suppositories, transdermal absorption It can be administered parenterally as an agent, inhalant and the like. In addition, an excipient, a binder, a wetting agent, a disintegrant, a lubricant and other pharmaceutical additives suitable for the dosage form are mixed with an effective amount of the present compound as needed to form a pharmaceutical preparation. it can. In the case of an injection, it is sterilized with a suitable carrier to give a preparation.
When administering the pharmaceutical composition of this invention, it can be administered by any method of orally and parenterally. Oral administration may be prepared and administered in a commonly used dosage form such as tablets, granules, powders, capsules and the like according to a conventional method. Parenteral administration can be suitably administered in any commonly used form such as injection. The compounds according to the present invention can be suitably used as an oral preparation because they have high oral absorbability.

  Various pharmaceutical additives such as excipients, binders, disintegrants, lubricants and the like suitable for the dosage form can be mixed with an effective amount of the compound of the present invention as needed to form a pharmaceutical composition.

The dose may vary depending on the disease state, administration route, patient's age, or body weight, but when administered orally to an adult, it is usually 0.1 to 100 mg / kg / day, preferably 1 to 20 mg / kg / day. It is a day.
It is desirable to set the dose of the pharmaceutical composition of the present invention in consideration of the patient's age, body weight, type and degree of disease, administration route, etc. It is 100 mg / kg / day, preferably in the range of 0.1 to 10 mg / kg / day. In the case of parenteral administration, although it largely depends on the administration route, it is usually 0.005 to 10 mg / kg / day, preferably 0.01 to 1 mg / kg / day. It may be administered once to several times a day.

  The compound of the present invention can be used in combination with other agents (hereinafter abbreviated as concomitant drugs) for the purpose of enhancing the action of the compound or reducing the dose of the compound. For example, in influenza diseases, neuraminidase inhibitors (eg, oseltamivir, zanamivir, peramivir and inavir etc.), RNA-dependent RNA polymerase inhibitors (eg, favipyravir), M2 protein inhibitors (eg, amandazine), PB2 Cap binding It may be used in combination with inhibitors (e.g. VX-787), anti-HA antibodies (e.g. MHAA4549A), or immune agonists (e.g. nitazoxanide). At this time, the administration time of the compound of the present invention and the concomitant drug is not limited, and these may be administered simultaneously to the administration subject, or may be administered with a time lag. Furthermore, the compound of the present invention and the concomitant drug may be administered as two or more preparations containing each active ingredient, or may be administered as a single preparation containing all the active ingredients.

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

  Hereinafter, the present invention will be described in more detail by way of Examples and Test Examples of the present invention, but the present invention is not limited thereto.

The NMR analysis obtained in the example was performed at 300 MHz and measured using DMSO-d ₆ and CDCl ₃ .
The term "RT" refers to retention time (minutes) in LC / MS (liquid chromatography / mass spectrometry), and the term "MS" refers to mass (M + H) in LC / MS.

(Measurement condition)
(1) Column: ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm i. D.2.1 x 50 mm) (Waters)
Flow rate: 0.8 mL / min; UV detection wavelength: 254 nm;
Mobile phase: [A] 0.1% formic acid-containing aqueous solution, [B] 0.1% formic acid-containing acetonitrile solution after performing a linear gradient of 5% to 100% solvent [B] for 3.5 minutes, 0.5 100% solvent [B] was maintained for one minute.

(2) Column: Shim-pack XR-ODS (2.2 μm, id 50 x 3.0 mm) (Shimadzu)
Flow rate: 1.6 mL / min; UV detection wavelength: 254 nm;
Mobile phase: [A] 0.1% formic acid-containing aqueous solution, [B] 0.1% formic acid-containing acetonitrile solution gradient: linear gradient of 10% to 100% solvent [B] in 3 minutes, 0.5 minutes , 100% solvent [B] was maintained.

第一工程
化合物１（２ｇ、８．６９ｍｍｏｌ）のアセトニトリル（５０ｍｌ）溶液に、氷冷下、トリエチルアミン（２．６４ｇ、２６．１ｍｍｏｌ）および4-アセトアミドベンゼンスルホニルアジド（２．３０ｇ、９．５７ｍｍｏｌ）を加え、室温で３０分間撹拌した。反応液を濃縮後、析出した固体をクロロホルムに懸濁させ、ろ去した。ろ液に１ｍｏｌ／Ｌ塩酸を加え、クロロホルムで抽出した。得られた有機層を硫酸ナトリウムで乾燥し、溶媒を留去した。析出した固体を酢酸エチルに懸濁させ、濾取、乾燥し、化合物２（１．６１ｇ、７２％）を得た。
MS: m/z = 257 [M+H]+, RT = 1.02 min.
1HNMR (DMSO-d6) δ:1.32 (6H, t, J = 7.2 Hz), 4.33 (4H, q, J = 7.2 Hz).
第二工程
化合物２（１．００ｇ、３．９３ｍｍｏｌ）のＤＭＦ（１０ｍｌ）溶液に室温下、炭酸カリウム（１．６２ｇ、１１．７２ｍｍｏｌ）を懸濁させ５分間撹拌した。懸濁液に、O-（2,4-ジニトロフェニル）ヒドロキシルアミン（９３２ｍｇ、４．６８ｍｍｏｌ）を加え、同温度で１時間撹拌した。反応液をクロロホルム（２０ｍｌ）で希釈し、１ｍｏｌ／Ｌ塩酸を加え、クロロホルムで抽出した。得られた有機層を硫酸ナトリウムで乾燥し、溶媒を留去した。析出した固体を酢酸エチルに懸濁させ、濾取、乾燥し、化合物３（８１８ｍｇ、７７％）を得た。
MS: m/z = 272 [M+H]+, RT = 1.08 min.
1HNMR (CDCl3) δ:1.42 (3H, t, J = 7.2 Hz), 1.45(3H, t, J = 7.2 Hz), 4.47 (2H, q, J = 7.2 Hz), 4.53 (2H, q, J = 7.2 Hz), 6.73 (2H, s).
第三工程
化合物３（１．００ｇ、３．６９ｍｍｏｌ）をＴＨＦ（２０ｍｌ）に懸濁させ、トリフェニルホスフィン（１．２６ｇ、４．８０ｍｍｏｌ）、ベンジルアルコール（５１９ｍｇ、４．８０ｍｍｏｌ）、ＤＩＡＤ（４０重量％トルエン溶液）（２．４３ｇ、４．８０ｍｍｏｌ）を加え、室温で３０分間撹拌した。溶媒を留去し、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）により精製して、化合物４（７３５ｍｇ、５５％）を得た。
MS: m/z = 362 [M+H]+, RT = 1.84 min.
1HNMR (CDCl3) δ:1.30 (3H, t, J = 7.2 Hz), 1.41 (3H, t, J = 7.2 Hz), 4.36 (2H, q, J = 7.2 Hz), 4.45 (2H, q, J = 7.2 Hz), 5.52 (2H, s), 5.58 (2H, s), 7.31-7.40 (5H, m).
第四工程
化合物４（３．００ｇ、８．３０ｍｍｏｌ）を酢酸（３０ｍｌ）に溶解させ、アリル3-ヒドロキシモルホリン-4-カルボキシレート（４．２０ｇ、２２．４３ｍｍｏｌ）を加え、８０℃で１時間撹拌した。反応液を放冷後、溶媒を留去し、得られた残渣をクロロホルムに溶解させ、飽和重曹水を加え、クロロホルムで抽出した。得られた有機層を硫酸ナトリウムで乾燥し、溶媒を留去し、化合物５の粗生成物を得た。
MS: m/z = 531 [M+H]+, RT = 2.17 min.
第五工程
化合物５の粗生成物をＴＨＦ（１５０ｍｌ）に溶解させ、モルフォリン（７．２３ｇ、８２．３ｍｍｏｌ）、テトラキストリフェニルホスフィンパラジウム（４８０ｍｇ、０．４１５ｍｍｏｌ）を加え、室温で１５時間撹拌した。反応液を濃縮後、析出した固体を酢酸エチルに懸濁させ、濾取、乾燥し、化合物６（１．８６ｇ、２工程収率５６％）を得た。
MS: m/z = 401 [M+H]+, RT = 1.53 min.
1HNMR (CDCl3) δ:1.40 (3H, t, J = 7.2 Hz), 2.88-3.03 (2H, m), 3.48-3.54 (1H, m), 3.99-4.09 (3H, m), 4.44 (2H, q, J = 7.2 Hz), 4.65-4.71 (1H, m), 5.40 (1H, d, J = 10.8 Hz), 5.59 (1H, d, J = 10.8 Hz), 5.88 (1H, d, J = 12.80 Hz), 7.30-7.38 (3H, m), 7.55-7.57 (2H, m).
第六工程
化合物６（１．５３ｇ、３．８２ｍｍｏｌ）を酢酸エチル（６０ｍｌ）に懸濁させ、Ｔ３Ｐ（５０重量％酢酸エチル溶液）（７．２９ｇ、１１．４６ｍｍｏｌ）、7,8-ジフルオロ-6,11-ジヒドロジベンゾ[b、e]チエピン-11-オール（１．５１ｇ、５．７１ｍｍｏｌ）、メタンスルホン酸（１．４７ｇ、１５．３０ｍｍｏｌ）を加え、６５℃で３０分間撹拌した。反応液を放冷後、飽和重曹水を加え、酢酸エチルで抽出した。得られた有機層を硫酸ナトリウムで乾燥し、溶媒を留去した。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７（１．４６ｇ、５９％）および化合物８（４８５ｍｇ、１９％）を得た。
化合物７
MS: m/z = 647 [M+H]+, RT = 2.79 min.
1HNMR (CDCl3) δ:1.31 (3H, t, J = 7.2 Hz), 2.91-2.99 (1H, m), 3.29-3.36 (2H, m), 3.75-3.79 (1H, m), 3.97-4.04 (2H, m), 4.26 (2H, q, J = 7.2 Hz), 4.53-4.56 (1H, m), 4.63-4.67 (1H, m), 5.09 (1H, s), 5.61 (1H, d, J = 11.20 Hz), 5.73-5.77 (1H, m), 5.84 (1H, d, J = 11.2 Hz), 6.14-6.17 (1H, m), 6.65-6.72 (1H, m), 7.08-7.12 (1H, m), 7.17-7.28 (3H, m), 7.32-7.40 (3H, m), 7.52-7.56 (2H, m).
化合物８
MS: m/z = 647 [M+H]+, RT = 2.66 min.
1HNMR (CDCl3) δ:1.37 (3H, t, J = 7.2 Hz), 3.03-3.10 (1H, m), 3.30-3.36 (2H, m), 3.76-3.80 (1H, m), 3.85-3.89 (1H, m), 3.63 (1H, d, J = 14.0 Hz), 4.23-4.36 (2H, m), 4.50-4.56 (1H, m), 4.67-4.71 (1H, m), 5.33 (1H, s), 5.60 (1H, d, J = 11.60 Hz), 5.74-5.79 (1H, m), 5.77 (1H, d, J = 11.6 Hz), 6.45 (1H, d, J = 7.6 Hz), 6.54-6.60 (1H, m), 6.97-7.03 (3H, m), 7.04-7.12 (1H, m), 7.31-7.39 (3H, m), 7.52-7.57 (2H, m).
第七工程
化合物８（４８５ｍｇ、０．７５０ｍｍｏｌ）をＴＨＦ（１０ｍｌ）に溶解させ、エタノール（５ｍｌ）、水（５ｍｌ）を加えた。反応液を０℃に冷却し、１ｍｏｌ／Ｌ水酸化ナトリウム水溶液（１ｍｌ）を加え、同温度で１５分間撹拌した。反応液に１ｍｏｌ／Ｌ塩酸（１ｍｌ）を加え、中和した。反応液に水を加え、クロロホルムで抽出した。得られた有機層を硫酸ナトリウムで乾燥し、溶媒を留去した。析出した固体をジイソプロピルエーテルに懸濁させ、濾取、乾燥し、化合物９（３８８ｍｇ、８２％）を得た。
MS: m/z = 619 [M+H]+, RT = 2.57 min.
第八工程
化合物９（３００ｍｇ、０．４８５ｍｍｏｌ）をＤＭＦ（５ｍｌ）に溶解させ、トリエチルアミン（２４５ｍｇ、２．４２ｍｍｏｌ）、ＤＰＰＡ（４００ｍｇ、１．４５ｍｍｏｌ）を加え、室温で１時間撹拌した。反応液を８０℃に昇温させ、同温度で２０分間撹拌した。反応液を０℃に冷却後、１ｍｏｌ／Ｌ水酸化ナトリウム水溶液（２ｍｌ）を加え、同温度で１０分間撹拌した。反応液に水を加え、１ｍｏｌ／Ｌ塩酸で中和した。反応液を酢酸エチルで抽出した。得られた有機層を重曹水および水で洗浄し、硫酸ナトリウムで乾燥し、溶媒を留去した。得られた残渣をシリカゲルクロマトグラフィー（酢酸エチルのみ）により精製し、化合物１０（１５０ｍｇ、５３％）を得た。
MS: m/z = 590 [M+H]+, RT = 2.36 min.
1HNMR (CDCl3) δ:3.03-3.10 (1H, m), 3.26-3.33 (2H, m), 3.73-3.80 (2H, m), 3.91 (1H, d, J = 14.0 Hz), 4.44-4.47 (1H, m), 4.64-4.68 (1H, m), 4.76 (2H, s), 5.35 (1H, s), 5.37 (1H, d, J = 10.8 Hz), 5.43 (1H, d, J = 10.8 Hz), 5.88-5.93 (1H, m), 6.60-6.65 (2H, m), 6.94-7.09 (4H, m), 7.29-7.38 (3H, m), 7.55-7.57 (2H, m).
第九工程
化合物１０（１５０ｍｇ、０．２５４ｍｍｏｌ）をＴＨＦ（２ｍｌ）に溶解させ、５０％次亜リン酸水溶液（２ｍｌ）を加えた。反応液を０℃に冷却し、同温度で、亜硝酸ナトリウム（３５ｍｇ、０．５０７ｍｍｏｌ）を加え、同温度で２０分間撹拌した。反応液に水を加え、酢酸エチルで抽出した。得られた有機層を硫酸ナトリウムで乾燥し、溶媒を留去した。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１１（８１ｍｇ、５５％）を得た。
MS: m/z = 575 [M+H]+, RT = 2.55 min.
1HNMR (CDCl3) δ:3.01-3.08 (1H, m), 3.25-3.33 (2H, m), 3.74-3.78 (1H, m), 3.82-3.86 (1H, m), 3.92 (1H, d, J = 14.4 Hz), 4.47-4.50 (1H, m), 4.66 (1H, d, J = 13.2 Hz), 5.31 (1H, s), 5.57 (1H, d, J = 11.6 Hz), 5.71-5.76 (2H, m), 6.43 (1H, d, J = 7.6 Hz), 6.54-6.58 (1H, m), 6.96-7.10 (4H, m), 7.18 (1H, s), 7.33-7.84 (3H, m), 7.55 (2H, d, J = 6.8 Hz).
第十工程
化合物１１（６６ｍｇ、０．１１５ｍｍｏｌ）をＤＭＡ（２ｍｌ）に溶解させ、塩化リチウム（９７．４ｍｇ、２．３０ｍｍｏｌ）を加え、８０℃で３０分間撹拌した。反応液を放冷後、酢酸エチル（１０ｍｌ）で希釈し、水を加え、１ｍｏｌ／Ｌ塩酸で中和し、酢酸エチルで抽出した。得られた有機層を水で洗浄し、硫酸ナトリウムで乾燥し、溶媒を留去した。析出した固体をジイソプロピルエーテルに懸濁させ、濾取、乾燥し、化合物Ｉ−１（３１ｍｇ、５６％）を得た。
MS: m/z = 485 [M+H]+, RT = 2.14 min.
1HNMR (CDCl3) δ:3.１1-3.19 (1H, m), 3.44-3.50 (1H, m), 3.52-3.58 (1H, m), 3.84-3.88 (1H, m), 3.95-3.98 (2H, m), 4.63-4.69 (1H, m), 5.34 (1H, s), 5.76 (1H, d, J = 14.0 Hz), 6.64 (1H, d, J = 7.6 Hz), 6.81 (1H, t, J = 6.4 Hz), 6.99-7.13 (4H, m), 7.18 (1H, s). Example 1

First Step Triethylamine (2.64 g, 26.1 mmol) and 4-acetamidobenzenesulfonyl azide (2.30 g, 9.57 mmol) in a solution of Compound 1 (2 g, 8.69 mmol) in acetonitrile (50 ml) under ice-cooling Was added and stirred at room temperature for 30 minutes. The reaction mixture was concentrated, and the precipitated solid was suspended in chloroform and filtered off. To the filtrate was added 1 mol / L hydrochloric acid, and the mixture was extracted with chloroform. The resulting organic layer was dried over sodium sulfate and the solvent was evaporated. The precipitated solid was suspended in ethyl acetate, collected by filtration and dried to give compound 2 (1.61 g, 72%).
MS: m / z = 257 [M + H] +, RT = 1.02 min.
1 H NMR (DMSO-d6) δ: 1.32 (6 H, t, J = 7.2 Hz), 4.33 (4 H, q, J = 7.2 Hz).
Second Step Potassium carbonate (1.62 g, 11.72 mmol) was suspended in a solution of compound 2 (1.00 g, 3.93 mmol) in DMF (10 ml) at room temperature and stirred for 5 minutes. To the suspension was added O- (2,4-dinitrophenyl) hydroxylamine (932 mg, 4.68 mmol) and stirred at the same temperature for 1 hour. The reaction solution was diluted with chloroform (20 ml), 1 mol / L hydrochloric acid was added, and the mixture was extracted with chloroform. The resulting organic layer was dried over sodium sulfate and the solvent was evaporated. The precipitated solid was suspended in ethyl acetate, collected by filtration and dried to give compound 3 (818 mg, 77%).
MS: m / z = 272 [M + H] +, RT = 1.08 min.
1 H NMR (CDCl 3) δ: 1.42 (3 H, t, J = 7.2 Hz), 1. 45 (3 H, t, J = 7.2 Hz), 4. 47 (2 H, q, J = 7.2 Hz), 4.53 (2 H, q, J = 7.2 Hz), 6.73 (2H, s).
Step 3 Compound 3 (1.00 g, 3.69 mmol) is suspended in THF (20 ml), triphenylphosphine (1.26 g, 4.80 mmol), benzyl alcohol (519 mg, 4.80 mmol), DIAD (40 mg) A weight percent toluene solution) (2.43 g, 4.80 mmol) was added and stirred at room temperature for 30 minutes. The solvent was evaporated, and the obtained residue was purified by silica gel chromatography (hexane-ethyl acetate) to give compound 4 (735 mg, 55%).
MS: m / z = 362 [M + H] +, RT = 1.84 min.
1H NMR (CDCl3) δ: 1.30 (3H, t, J = 7.2 Hz), 1.41 (3H, t, J = 7.2 Hz), 4.36 (2H, q, J = 7.2 Hz), 4.45 (2H, q, J = 7.2 Hz), 5.52 (2H, s), 5.58 (2H, s), 7.31-7.40 (5H, m).
Fourth Step Compound 4 (3.00 g, 8.30 mmol) is dissolved in acetic acid (30 ml), allyl 3-hydroxymorpholine-4-carboxylate (4.20 g, 22.43 mmol) is added, and the mixture is heated at 80 ° C. for 1 hour It stirred. The reaction solution is allowed to cool, and the solvent is evaporated. The obtained residue is dissolved in chloroform, saturated aqueous sodium bicarbonate solution is added, and the mixture is extracted with chloroform. The obtained organic layer was dried over sodium sulfate and the solvent was evaporated to give a crude product of compound 5.
MS: m / z = 531 [M + H] +, RT = 2.17 min.
Fifth step The crude product of compound 5 is dissolved in THF (150 ml), morpholine (7.23 g, 82.3 mmol), tetrakistriphenylphosphine palladium (480 mg, 0.415 mmol) are added and stirred at room temperature for 15 hours did. The reaction mixture was concentrated, and the precipitated solid was suspended in ethyl acetate, collected by filtration and dried to give compound 6 (1.86 g, 56% yield over two steps).
MS: m / z = 401 [M + H] +, RT = 1.53 min.
1H NMR (CDCl3) δ: 1.40 (3H, t, J = 7.2 Hz), 2.88-3.03 (2H, m), 3.48-3.54 (1H, m), 3.99-4.09 (3H, m), 4.44 (2H, q , J = 7.2 Hz), 4.65-4.71 (1 H, m), 5. 40 (1 H, d, J = 10.8 Hz), 5. 59 (1 H, d, J = 10.8 Hz), 5. 88 (1 H, d, J = 12.80 Hz) ), 7.30-7.38 (3H, m), 7.55-7.57 (2H, m).
Sixth Step Compound 6 (1.53 g, 3.82 mmol) is suspended in ethyl acetate (60 ml), T3P (50% by weight solution in ethyl acetate) (7.29 g, 11.46 mmol), 7,8-difluoro- 6,11-Dihydrodibenzo [b, e] thiepin-11-ol (1.51 g, 5.71 mmol), methanesulfonic acid (1.47 g, 15.30 mmol) were added and stirred at 65 ° C. for 30 minutes. The reaction mixture was allowed to cool, saturated aqueous sodium bicarbonate solution was added, and the mixture was extracted with ethyl acetate. The resulting organic layer was dried over sodium sulfate and the solvent was evaporated. The resulting residue was purified by silica gel chromatography (hexane-ethyl acetate) to give compound 7 (1.46 g, 59%) and compound 8 (485 mg, 19%).
Compound 7
MS: m / z = 647 [M + H] +, RT = 2.79 min.
1 H NMR (CDCl 3) δ: 1.31 (3 H, t, J = 7.2 Hz), 2.91-2.99 (1 H, m), 3.29-3.36 (2 H, m), 3.75-3. 79 (1 H, m), 3.97-4.04 (2 H , m), 4.26 (2H, q, J = 7.2 Hz), 4.53-4.56 (1H, m), 4.63-4.67 (1H, m), 5.09 (1H, s), 5.61 (1H, d, J = 11.20 Hz), 5.73-5.77 (1 H, m), 5. 84 (1 H, d, J = 11.2 Hz), 6.14-6.17 (1 H, m), 6.65-6.72 (1 H, m), 7.08-7.12 (1 H, m) , 7.17-7.28 (3H, m), 7.32-7.40 (3H, m), 7.52-7.56 (2H, m).
Compound 8
MS: m / z = 647 [M + H] +, RT = 2.66 min.
1 H NMR (CDCl 3) δ: 1.37 (3 H, t, J = 7.2 Hz), 3.03-3.10 (1 H, m), 3.30-3.36 (2 H, m), 3.76-3. 80 (1 H, m), 3.85-3. 89 (1 H , m), 3.63 (1H, d, J = 14.0 Hz), 4.23-4.36 (2H, m), 4.50-4.56 (1H, m), 4.67-4.71 (1H, m), 5.33 (1H, s), 5.60 (1H, d, J = 11.60 Hz), 5.74-5.79 (1 H, m), 5. 77 (1 H, d, J = 11.6 Hz), 6.45 (1 H, d, J = 7.6 Hz), 6.54-6.60 (1 H , m), 6.97-7.03 (3H, m), 7.04-7.12 (1H, m), 7.31-7. 39 (3H, m), 7.52-7.57 (2H, m).
Seventh Step Compound 8 (485 mg, 0.750 mmol) was dissolved in THF (10 ml), and ethanol (5 ml) and water (5 ml) were added. The reaction solution was cooled to 0 ° C., 1 mol / L aqueous sodium hydroxide solution (1 ml) was added, and the mixture was stirred at the same temperature for 15 minutes. The reaction mixture was neutralized by adding 1 mol / L hydrochloric acid (1 ml). Water was added to the reaction solution, and extracted with chloroform. The resulting organic layer was dried over sodium sulfate and the solvent was evaporated. The precipitated solid was suspended in diisopropyl ether, collected by filtration and dried to give compound 9 (388 mg, 82%).
MS: m / z = 619 [M + H] +, RT = 2.57 min.
Eighth Step Compound 9 (300 mg, 0.485 mmol) was dissolved in DMF (5 ml), triethylamine (245 mg, 2.42 mmol), DPPA (400 mg, 1.45 mmol) were added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was heated to 80 ° C. and stirred at the same temperature for 20 minutes. The reaction mixture was cooled to 0 ° C., 1 mol / L aqueous sodium hydroxide solution (2 ml) was added, and the mixture was stirred at the same temperature for 10 minutes. Water was added to the reaction solution and neutralized with 1 mol / L hydrochloric acid. The reaction solution was extracted with ethyl acetate. The obtained organic layer was washed with aqueous sodium bicarbonate solution and water, dried over sodium sulfate, and the solvent was evaporated. The resulting residue was purified by silica gel chromatography (ethyl acetate only) to give compound 10 (150 mg, 53%).
MS: m / z = 590 [M + H] +, RT = 2.36 min.
1H NMR (CDCl3) δ: 3.03-3.10 (1H, m), 3.26-3.33 (2H, m), 3.73-3.80 (2H, m), 3.91 (1H, d, J = 14.0 Hz), 4.44-4.47 (1H , m), 4.64-4.68 (1 H, m), 4. 76 (2 H, s), 5. 35 (1 H, s), 5. 37 (1 H, d, J = 10.8 Hz), 5.43 (1 H, d, J = 10.8 Hz) , 5.88-5.93 (1H, m), 6.60-6.65 (2H, m), 6.94-7.09 (4H, m), 7.29-7.38 (3H, m), 7.55-7.57 (2H, m).
Step 9 Compound 10 (150 mg, 0.254 mmol) was dissolved in THF (2 ml), and 50% aqueous solution of hypophosphorous acid (2 ml) was added. The reaction solution was cooled to 0 ° C., sodium nitrite (35 mg, 0.507 mmol) was added at the same temperature, and the mixture was stirred at the same temperature for 20 minutes. Water was added to the reaction solution, and extracted with ethyl acetate. The resulting organic layer was dried over sodium sulfate and the solvent was evaporated. The obtained residue was purified by silica gel chromatography (hexane-ethyl acetate) to give compound 11 (81 mg, 55%).
MS: m / z = 575 [M + H] +, RT = 2.55 min.
1H NMR (CDCl3) δ: 3.01-3.08 (1H, m), 3.25-3.33 (2H, m), 3.74-3.78 (1H, m), 3.82-3.86 (1H, m), 3.92 (1H, d, J = 14.4 Hz), 4.47-4.50 (1H, m), 4.66 (1H, d, J = 13.2 Hz), 5.31 (1H, s), 5.57 (1 H, d, J = 11.6 Hz), 5.71-5. 76 (2H, 2H) m), 6.43 (1H, d, J = 7.6 Hz), 6.54-6.58 (1H, m), 6.96-7.10 (4H, m), 7.18 (1H, s), 7.33-7.84 (3H, m), 7.55 (2H, d, J = 6.8 Hz).
Tenth Step Compound 11 (66 mg, 0.115 mmol) was dissolved in DMA (2 ml), lithium chloride (97.4 mg, 2.30 mmol) was added, and the mixture was stirred at 80 ° C. for 30 minutes. The reaction mixture was allowed to cool and then diluted with ethyl acetate (10 ml), water was added, the mixture was neutralized with 1 mol / L hydrochloric acid, and extracted with ethyl acetate. The resulting organic layer was washed with water, dried over sodium sulfate and evaporated. The precipitated solid was suspended in diisopropyl ether, collected by filtration and dried to give compound I-1 (31 mg, 56%).
MS: m / z = 485 [M + H] +, RT = 2.14 min.
1H NMR (CDCl3) δ: 3.11-3.19 (1H, m), 3.44-3.50 (1H, m), 3.52-3.58 (1H, m), 3.84-3.88 (1H, m), 3.95-3.98 (2H, 2H, m) m), 4.63-4.69 (1 H, m), 5.34 (1 H, s), 5. 76 (1 H, d, J = 14.0 Hz), 6.64 (1 H, d, J = 7.6 Hz), 6.81 (1 H, t, J = 6.4 Hz), 6.99-7. 13 (4H, m), 7.18 (1 H, s).

第一工程
化合物４（３．９６ｇ、１０．９５ｍｍｏｌ）のＴＨＦ（１００ｍ）‐エタノール（１００ｍｌ）混合溶液に、氷冷下、１ｍｏｌ／Ｌ水酸化ナトリウム水溶液（２ｍｌ）を加え、同温度で、３０分間撹拌した。反応液を１ｍｏｌ／Ｌ塩酸（２ｍｌ）で中和し、溶媒を減圧留去した。得られた残渣に水を加え、クロロホルムで抽出した。得られた有機層を硫酸ナトリウムで乾燥し、溶媒を留去し、化合物１２（３．２３ｇ、８８％）を得た。
MS: m/z = 334 [M+H]+, RT = 1.91 min.
1HNMR (CDCl3) δ:1.34 (3H, t, J = 7.2 Hz), 4.43 (2H, d, J = 7.2 Hz), 5.65 (2H, s), 6.02 (2H, s), 7.33-7.41 (5H, m), 15.01 (1H, brs).
第二工程
化合物１２（２．８５ｇ、８．５５ｍｍｏｌ）を、エチルアミン水溶液（６６．０〜７２．０重量％）（２０ｍｌ）に溶解させ、室温で３０分間撹拌した。反応液を濃縮後、水を加え、２ｍｏｌ／Ｌ塩酸で中和し、クロロホルムで抽出した。得られ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。得られた残渣を酢酸エチル‐ジイソプロピルエーテル混合溶液（１：１）に懸濁させ、濾取、乾燥し、化合物１３（２．０８ｇ、７３％）を得た。
MS: m/z = 333 [M+H]+, RT = 1.55 min.
1HNMR (CDCl3) δ:1.12 (3H, t, J = 7.2 Hz), 3.36-3.42 (2H, m), 5.67 (2H, s), 5.56 (1H, brs), 6.81 (1H, brs), 7.35-7.40 (5H, m), 15.39 (1H, brs).
第三工程
化合物１３（１．７０ｇ、５．１２ｍｍｏｌ）のＤＭＦ（１５ｍｌ）溶液に、パラホルムアルデヒド（１５４ｍｇ、５．１２ｍｍｏｌ）と酢酸（１２０ｍｇ、２．００ｍｍｏｌ）を加え、１２０℃で２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１４（４７９ｍｇ、２７％）を得た。
MS: m/z = 345 [M+H]+, RT = 1.51 min.
1HNMR (CDCl3) δ:1.28 (3H, t, J = 7.2 Hz), 3.63 (2H, d, J = 7.2 Hz), 4.62 (2H, d, J = 4.8 Hz), 5.69 (2H, s), 7.30-7.37 (3H, m), 7.52-7.54 (2H, m), 7.97 (1H, brs), 15.44 (1H, brs).
第四工程
化合物１４（１．７０ｇ、５．１２ｍｍｏｌ）を、酢酸エチル（１０ｍｌ）に懸濁させ、Ｔ３Ｐ（５０重量％酢酸エチル溶液）（１．４８ｇ、１０．２４ｍｍｏｌ）、ジベンゾスベロール（３６６ｍｇ、１．７４ｍｍｏｌ）を加え、３０分間加熱還流した。反応液を放冷後、水を加え、酢酸エチルで抽出した。得られた有機層を、硫酸ナトリウムで乾燥し、溶媒を減圧留去した。析出した固体を酢酸エチルに懸濁させ、濾取、乾燥し、化合物１５（５８１ｍｇ、９３％）を得た。
MS: m/z = 537 [M+H]+, RT = 2.66 min.
1HNMR (CDCl3) δ:1.28 (3H, t, J = 7.2 Hz), 2.81-2.85 (1H, m), 2.96-3.03 (1H, m), 3.21-3.26 (1H, m), 3.75-3.81 (1H, m), 4.10-4.17 (1H, m), 4.29 (1H, d, J = 14.0 Hz), 4.50-4.57 (1H, m), 4.83 (1H, d, J = 14.0 Hz), 5.63 (1H, d, J =11.2 Hz), 5.77 (1H, d, J = 11.2 Hz), 6.35-6.37 (1H, m), 6.62 (1H, brs), 7.07 (2H, brs), 7.15-7.25 (2H, m), 7.28-7.41 (5H, m), 7.54-7.56 (2H, m), 14.26 (1H, brs).
第五工程
化合物１５（５００ｍｇ、０．９３２ｍｍｏｌ）をＤＭＦ（１０ｍｌ）に溶解させ、トリエチルアミン（４７１ｍｇ、４．６５ｍｍｏｌ）、ＤＰＰＡ（７６９ｍｇ、２．７９ｍｍｏｌ）を加え、室温で１時間撹拌した。反応液を８０℃に昇温させ、同温度で２０分間撹拌した。反応液を０℃に冷却後、１ｍｏｌ／Ｌ水酸化ナトリウム水溶液（４ｍｌ）を加え、同温度で１０分間撹拌した。反応液に水を加え、１ｍｏｌ／Ｌ塩酸で中和した。反応液を酢酸エチルで抽出した。得られた有機層を重曹水および水で洗浄し、硫酸ナトリウムで乾燥し、溶媒を留去した。得られた残渣を得られた残渣を酢酸エチル‐ジイソプロピルエーテル混合溶液（１：１）に懸濁させ、濾取、乾燥し、化合物１６（３７１ｍｇ、７８％）を得た。
MS: m/z = 508 [M+H]+, RT = 2.39 min.
1HNMR (CDCl3) δ:1.17 (3H, t, J = 7.2 Hz), 2.77-2.83 (1H, m), 2.93-3.04 (2H, m), 3.62-3.69 (1H, m), 4.07 (1H, d, J = 13.6 Hz), 4.13-4.23 (1H, m), 4.40-4.47 (1H, m), 4.62 (2H, s), 4.70 (1H, d, J = 13.6 Hz), 5.02 (1H, s), 5.41 (1H, s), 6.58 (1H, d, J = 7.2 Hz), 6.78-6.81 (1H, m), 7.08-7.22 (4H, m), 7.27-7.37 (5H, m), 7.60-7.62 (2H, m).
第六工程
化合物１６（３００ｍｇ、０．５９１ｍｍｏｌ）をＴＨＦ（５ｍｌ）に溶解させ、５０％次亜リン酸水溶液（５ｍｌ）を加えた。反応液を０℃に冷却し、同温度で、亜硝酸ナトリウム（８２ｍｇ、１．１９ｍｍｏｌ）を加え、同温度で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。得られた有機層を飽和重曹水で洗浄し、硫酸ナトリウムで乾燥し、溶媒を留去した。得られた残渣を酢酸エチルに懸濁させ、濾取、乾燥し、化合物１７（７７ｍｇ、２６％）を得た。
MS: m/z = 493 [M+H]+, RT = 2.56 min.
1HNMR (CDCl3) δ:1.17 (3H, t, J = 7.2 Hz), 2.77-2.83 (1H, m), 2.89-3.01 (2H, m), 3.61-3.68 (1H, m), 4.09 (1H, d, J = 13.6 Hz), 4.19-4.28 (1H, m), 4.33-4.40 (1H, m), 4.74 (1H, d, J = 13.6 Hz), 5.01 (1H, s), 5.56 (1H, d, J = 11.2 Hz), 5.65 (1H, d, J = 11.2 Hz), 6.45 (1H, d, J = 7.6 Hz), 6.73 (1H, t, J = 7.2 Hz), 7.05-7.11 (2H, m), 7.14-7.22 (2H, m), 7.17 (1H, s), 7.26-7.38 (5H, m), 7.58-7.60 (2H, m).
第七工程
化合物１７（６8ｍｇ、０．１３８ｍｍｏｌ）をＤＭＡ（１ｍｌ）に溶解させ、塩化リチウム（１１７ｍｇ、２．７６ｍｍｏｌ）を加え、８０℃で２０分間撹拌した。反応液を放冷後、酢酸エチル（１０ｍｌ）で希釈し、水を加え、１ｍｏｌ／Ｌ塩酸で中和し、酢酸エチルで抽出した。得られた有機層を水で洗浄し、硫酸ナトリウムで乾燥し、溶媒を留去した。析出した固体をジイソプロピルエーテルに懸濁させ、濾取、乾燥し、化合物Ｉ−２（２７ｍｇ、４９％）を得た。
MS: m/z = 403 [M+H]+, RT = 2.15 min.
1HNMR (CDCl3) δ:1.24 (3H, t, J = 7.2 Hz), 2.85-2.88 (1H, m), 2.94-3.01 (1H, m), 3.17 (1H, brs), 3.74-3.78 (1H, m), 4.00 ( 1H, brs), 4.24-4.33 (2H, m), 4.91 (1H, d, J = 12.4 Hz), 5.08 (1H, s), 6.61 (1H, brs), 6.89 (1H, brs), 7.11-7.31 (6H, m), 7.13 (1H, s). Example 2

First step: To a mixed solution of compound 4 (3.96 g, 10.95 mmol) in THF (100 m) -ethanol (100 ml) was added 1 mol / L aqueous sodium hydroxide solution (2 ml) under ice-cooling, and Stir for a minute. The reaction solution was neutralized with 1 mol / L hydrochloric acid (2 ml), and the solvent was evaporated under reduced pressure. Water was added to the obtained residue, and extracted with chloroform. The obtained organic layer was dried over sodium sulfate and the solvent was evaporated to give compound 12 (3.23 g, 88%).
MS: m / z = 334 [M + H] +, RT = 1.91 min.
1H NMR (CDCl3) δ: 1.34 (3H, t, J = 7.2 Hz), 4.43 (2H, d, J = 7.2 Hz), 5.65 (2H, s), 6.02 (2H, s), 7.33-7.41 (5H, m), 15.01 (1 H, brs).
Second Step Compound 12 (2.85 g, 8.55 mmol) was dissolved in aqueous ethylamine solution (66.0 to 72.0 wt%) (20 ml) and stirred at room temperature for 30 minutes. The reaction mixture was concentrated, water was added, the mixture was neutralized with 2 mol / L hydrochloric acid, and extracted with chloroform. The obtained organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was suspended in ethyl acetate-diisopropyl ether mixed solution (1: 1), collected by filtration, and dried to give compound 13 (2.08 g, 73%).
MS: m / z = 333 [M + H] +, RT = 1.55 min.
1H NMR (CDCl3) δ: 1.12 (3H, t, J = 7.2 Hz), 3.36-3.42 (2H, m), 5.67 (2H, s), 5.56 (1H, brs), 6.81 (1H, brs), 7.35- 7.40 (5H, m), 15.39 (1H, brs).
Third step To a solution of compound 13 (1.70 g, 5.12 mmol) in DMF (15 ml), paraformaldehyde (154 mg, 5.12 mmol) and acetic acid (120 mg, 2.00 mmol) were added and stirred at 120 ° C. for 2 hours . The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel chromatography (chloroform-methanol) to give compound 14 (479 mg, 27%).
MS: m / z = 345 [M + H] +, RT = 1.51 min.
1H NMR (CDCl3) δ: 1.28 (3H, t, J = 7.2 Hz), 3.63 (2H, d, J = 7.2 Hz), 4.62 (2H, d, J = 4.8 Hz), 5.69 (2H, s), 7.30 -7.37 (3H, m), 7.52-7.54 (2H, m), 7.97 (1H, brs), 15.44 (1H, brs).
Fourth Step Compound 14 (1.70 g, 5.12 mmol) is suspended in ethyl acetate (10 ml), T3P (50% by weight solution in ethyl acetate) (1.48 g, 10.24 mmol), dibenzosuberol (366 mg) , 1.74 mmol) was added and heated to reflux for 30 minutes. The reaction mixture was allowed to cool, water was added, and the mixture was extracted with ethyl acetate. The obtained organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure. The precipitated solid was suspended in ethyl acetate, collected by filtration and dried to give compound 15 (581 mg, 93%).
MS: m / z = 537 [M + H] +, RT = 2.66 min.
1 H NMR (CDCl 3) δ: 1.28 (3 H, t, J = 7.2 Hz), 2.81-2.85 (1 H, m), 2.96-3.03 (1 H, m), 3.21-3.26 (1 H, m), 3.75-3.81 (1 H , m), 4.10-4.17 (1H, m), 4.29 (1H, d, J = 14.0 Hz), 4.50-4.57 (1H, m), 4.83 (1 H, d, J = 14.0 Hz), 5.63 (1H, 1 5 d, J = 11.2 Hz), 5. 77 (1 H, d, J = 11.2 Hz), 6.35-6. 37 (1 H, m), 6.62 (1 H, brs), 7.07 (2 H, brs), 7.15-7. 25 (2 H, m) ), 7.28-7.41 (5H, m), 7.54-7.56 (2H, m), 14.26 (1H, brs).
Fifth Step Compound 15 (500 mg, 0.932 mmol) was dissolved in DMF (10 ml), triethylamine (471 mg, 4.65 mmol), DPPA (769 mg, 2.79 mmol) were added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was heated to 80 ° C. and stirred at the same temperature for 20 minutes. The reaction mixture was cooled to 0 ° C., 1 mol / L aqueous sodium hydroxide solution (4 ml) was added, and the mixture was stirred at the same temperature for 10 minutes. Water was added to the reaction solution and neutralized with 1 mol / L hydrochloric acid. The reaction solution was extracted with ethyl acetate. The obtained organic layer was washed with aqueous sodium bicarbonate solution and water, dried over sodium sulfate, and the solvent was evaporated. The obtained residue was suspended in a mixed solution of ethyl acetate-diisopropyl ether (1: 1), collected by filtration and dried to give compound 16 (371 mg, 78%).
MS: m / z = 508 [M + H] +, RT = 2.39 min.
1H NMR (CDCl3) δ: 1.17 (3H, t, J = 7.2 Hz), 2.77-2.83 (1H, m), 2.93-3.04 (2H, m), 3.62-3.69 (1H, m), 4.07 (1H, d , J = 13.6 Hz), 4.13-4.23 (1H, m), 4.40-4.47 (1 H, m), 4.62 (2 H, s), 4.70 (1 H, d, J = 13.6 Hz), 5.02 (1 H, s) , 5.41 (1H, s), 6.58 (1H, d, J = 7.2 Hz), 6.78-6.81 (1H, m), 7.08-7.22 (4H, m), 7.27-7.37 (5H, m), 7.60-7.62 (2H, m).
Sixth Step Compound 16 (300 mg, 0.591 mmol) was dissolved in THF (5 ml), and 50% aqueous solution of hypophosphorous acid (5 ml) was added. The reaction solution was cooled to 0 ° C., and sodium nitrite (82 mg, 1.19 mmol) was added at the same temperature, and the mixture was stirred for 30 minutes at the same temperature. Water was added to the reaction solution, and extracted with ethyl acetate. The obtained organic layer was washed with saturated aqueous sodium bicarbonate solution, dried over sodium sulfate and the solvent was evaporated. The obtained residue was suspended in ethyl acetate, collected by filtration and dried to give compound 17 (77 mg, 26%).
MS: m / z = 493 [M + H] +, RT = 2.56 min.
1H NMR (CDCl3) δ: 1.17 (3H, t, J = 7.2 Hz), 2.77-2.83 (1H, m), 2.89-3.01 (2H, m), 3.61-3.68 (1H, m), 4.09 (1H, d , J = 13.6 Hz), 4.19-4.28 (1 H, m), 4.33-4.40 (1 H, m), 4.74 (1 H, d, J = 13.6 Hz), 5.01 (1 H, s), 5.56 (1 H, d, J = 11.2 Hz), 5.65 (1 H, d, J = 11.2 Hz), 6. 45 (1 H, d, J = 7.6 Hz), 6.73 (1 H, t, J = 7.2 Hz), 7.05-7.11 (2 H, m) , 7.14-7.22 (2H, m), 7.17 (1H, s), 7.26-7.38 (5H, m), 7.58-7.60 (2H, m).
Seventh Step Compound 17 (68 mg, 0.138 mmol) was dissolved in DMA (1 ml), lithium chloride (117 mg, 2.76 mmol) was added, and the mixture was stirred at 80 ° C. for 20 minutes. The reaction mixture was allowed to cool and then diluted with ethyl acetate (10 ml), water was added, the mixture was neutralized with 1 mol / L hydrochloric acid, and extracted with ethyl acetate. The resulting organic layer was washed with water, dried over sodium sulfate and evaporated. The precipitated solid was suspended in diisopropyl ether, collected by filtration and dried to give compound I-2 (27 mg, 49%).
MS: m / z = 403 [M + H] +, RT = 2.15 min.
1H NMR (CDCl3) δ: 1.24 (3 H, t, J = 7.2 Hz), 2.85-2.88 (1 H, m), 2.94-3.01 (1 H, m), 3.17 (1 H, brs), 3.74-3. 78 (1 H, m ), 4.00 (1H, brs), 4.24-4.33 (2H, m), 4.91 (1H, d, J = 12.4 Hz), 5.08 (1H, s), 6.61 (1H, brs), 6.89 (1H, brs) , 7.1 1-7.31 (6H, m), 7.13 (1 H, s).

The following example compounds were synthesized according to the same method as the above example.

Physical data of each compound is shown below.

(A, B, R1, R2, R4) ＝ (A1, B1, R1-1, R2-1, R4-1)、(A1, B1, R1-1, R2-1, R4-2)、(A1, B1, R1-1, R2-1, R4-3)、(A1, B1, R1-1, R2-1, R4-4)、(A1, B1, R1-1, R2-1, R4-5)、(A1, B1, R1-1, R2-2, R4-1)、(A1, B1, R1-1, R2-2, R4-2)、(A1, B1, R1-1, R2-2, R4-3)、(A1, B1, R1-1, R2-2, R4-4)、(A1, B1, R1-1, R2-2, R4-5)、(A1, B1, R1-1, R2-3, R4-1)、(A1, B1, R1-1, R2-3, R4-2)、(A1, B1, R1-1, R2-3, R4-3)、(A1, B1, R1-1, R2-3, R4-4)、(A1, B1, R1-1, R2-3, R4-5)、(A1, B1, R1-1, R2-4, R4-1)、(A1, B1, R1-1, R2-4, R4-2)、(A1, B1, R1-1, R2-4, R4-3)、(A1, B1, R1-1, R2-4, R4-4)、(A1, B1, R1-1, R2-4, R4-5)、(A1, B1, R1-1, R2-5, R4-1)、(A1, B1, R1-1, R2-5, R4-2)、(A1, B1, R1-1, R2-5, R4-3)、(A1, B1, R1-1, R2-5, R4-4)、(A1, B1, R1-1, R2-5, R4-5)、(A1, B1, R1-2, R2-1, R4-1)、(A1, B1, R1-2, R2-1, R4-2)、(A1, B1, R1-2, R2-1, R4-3)、(A1, B1, R1-2, R2-1, R4-4)、(A1, B1, R1-2, R2-1, R4-5)、(A1, B1, R1-2, R2-2, R4-1)、(A1, B1, R1-2, R2-2, R4-2)、(A1, B1, R1-2, R2-2, R4-3)、(A1, B1, R1-2, R2-2, R4-4)、(A1, B1, R1-2, R2-2, R4-5)、(A1, B1, R1-2, R2-3, R4-1)、(A1, B1, R1-2, R2-3, R4-2)、(A1, B1, R1-2, R2-3, R4-3)、(A1, B1, R1-2, R2-3, R4-4)、(A1, B1, R1-2, R2-3, R4-5)、(A1, B1, R1-2, R2-4, R4-1)、(A1, B1, R1-2, R2-4, R4-2)、(A1, B1, R1-2, R2-4, R4-3)、(A1, B1, R1-2, R2-4, R4-4)、(A1, B1, R1-2, R2-4, R4-5)、(A1, B1, R1-2, R2-5, R4-1)、(A1, B1, R1-2, R2-5, R4-2)、(A1, B1, R1-2, R2-5, R4-3)、(A1, B1, R1-2, R2-5, R4-4)、(A1, B1, R1-2, R2-5, R4-5)、(A1, B1, R1-3, R2-1, R4-1)、(A1, B1, R1-3, R2-1, R4-2)、(A1, B1, R1-3, R2-1, R4-3)、(A1, B1, R1-3, R2-1, R4-4)、(A1, B1, R1-3, R2-1, R4-5)、(A1, B1, R1-3, R2-2, R4-1)、(A1, B1, R1-3, R2-2, R4-2)、(A1, B1, R1-3, R2-2, R4-3)、(A1, B1, R1-3, R2-2, R4-4)、(A1, B1, R1-3, R2-2, R4-5)、(A1, B1, R1-3, R2-3, R4-1)、(A1, B1, R1-3, R2-3, R4-2)、(A1, B1, R1-3, R2-3, R4-3)、(A1, B1, R1-3, R2-3, R4-4)、(A1, B1, R1-3, R2-3, R4-5)、(A1, B1, R1-3, R2-4, R4-1)、(A1, B1, R1-3, R2-4, R4-2)、(A1, B1, R1-3, R2-4, R4-3)、(A1, B1, R1-3, R2-4, R4-4)、(A1, B1, R1-3, R2-4, R4-5)、(A1, B1, R1-3, R2-5, R4-1)、(A1, B1, R1-3, R2-5, R4-2)、(A1, B1, R1-3, R2-5, R4-3)、(A1, B1, R1-3, R2-5, R4-4)、(A1, B1, R1-3, R2-5, R4-5)、(A1, B2, R1-1, R2-1, R4-1)、(A1, B2, R1-1, R2-1, R4-2)、(A1, B2, R1-1, R2-1, R4-3)、(A1, B2, R1-1, R2-1, R4-4)、(A1, B2, R1-1, R2-1, R4-5)、(A1, B2, R1-1, R2-2, R4-1)、(A1, B2, R1-1, R2-2, R4-2)、(A1, B2, R1-1, R2-2, R4-3)、(A1, B2, R1-1, R2-2, R4-4)、(A1, B2, R1-1, R2-2, R4-5)、(A1, B2, R1-1, R2-3, R4-1)、(A1, B2, R1-1, R2-3, R4-2)、(A1, B2, R1-1, R2-3, R4-3)、(A1, B2, R1-1, R2-3, R4-4)、(A1, B2, R1-1, R2-3, R4-5)、(A1, B2, R1-1, R2-4, R4-1)、(A1, B2, R1-1, R2-4, R4-2)、(A1, B2, R1-1, R2-4, R4-3)、(A1, B2, R1-1, R2-4, R4-4)、(A1, B2, R1-1, R2-4, R4-5)、(A1, B2, R1-1, R2-5, R4-1)、(A1, B2, R1-1, R2-5, R4-2)、(A1, B2, R1-1, R2-5, R4-3)、(A1, B2, R1-1, R2-5, R4-4)、(A1, B2, R1-1, R2-5, R4-5)、(A1, B2, R1-2, R2-1, R4-1)、(A1, B2, R1-2, R2-1, R4-2)、(A1, B2, R1-2, R2-1, R4-3)、(A1, B2, R1-2, R2-1, R4-4)、(A1, B2, R1-2, R2-1, R4-5)、(A1, B2, R1-2, R2-2, R4-1)、(A1, B2, R1-2, R2-2, R4-2)、(A1, B2, R1-2, R2-2, R4-3)、(A1, B2, R1-2, R2-2, R4-4)、(A1, B2, R1-2, R2-2, R4-5)、(A1, B2, R1-2, R2-3, R4-1)、(A1, B2, R1-2, R2-3, R4-2)、(A1, B2, R1-2, R2-3, R4-3)、(A1, B2, R1-2, R2-3, R4-4)、(A1, B2, R1-2, R2-3, R4-5)、(A1, B2, R1-2, R2-4, R4-1)、(A1, B2, R1-2, R2-4, R4-2)、(A1, B2, R1-2, R2-4, R4-3)、(A1, B2, R1-2, R2-4, R4-4)、(A1, B2, R1-2, R2-4, R4-5)、(A1, B2, R1-2, R2-5, R4-1)、(A1, B2, R1-2, R2-5, R4-2)、(A1, B2, R1-2, R2-5, R4-3)、(A1, B2, R1-2, R2-5, R4-4)、(A1, B2, R1-2, R2-5, R4-5)、(A1, B2, R1-3, R2-1, R4-1)、(A1, B2, R1-3, R2-1, R4-2)、(A1, B2, R1-3, R2-1, R4-3)、(A1, B2, R1-3, R2-1, R4-4)、(A1, B2, R1-3, R2-1, R4-5)、(A1, B2, R1-3, R2-2, R4-1)、(A1, B2, R1-3, R2-2, R4-2)、(A1, B2, R1-3, R2-2, R4-3)、(A1, B2, R1-3, R2-2, R4-4)、(A1, B2, R1-3, R2-2, R4-5)、(A1, B2, R1-3, R2-3, R4-1)、(A1, B2, R1-3, R2-3, R4-2)、(A1, B2, R1-3, R2-3, R4-3)、(A1, B2, R1-3, R2-3, R4-4)、(A1, B2, R1-3, R2-3, R4-5)、(A1, B2, R1-3, R2-4, R4-1)、(A1, B2, R1-3, R2-4, R4-2)、(A1, B2, R1-3, R2-4, R4-3)、(A1, B2, R1-3, R2-4, R4-4)、(A1, B2, R1-3, R2-4, R4-5)、(A1, B2, R1-3, R2-5, R4-1)、(A1, B2, R1-3, R2-5, R4-2)、(A1, B2, R1-3, R2-5, R4-3)、(A1, B2, R1-3, R2-5, R4-4)、(A1, B2, R1-3, R2-5, R4-5)、(A1, B3, R1-1, R2-1, R4-1)、(A1, B3, R1-1, R2-1, R4-2)、(A1, B3, R1-1, R2-1, R4-3)、(A1, B3, R1-1, R2-1, R4-4)、(A1, B3, R1-1, R2-1, R4-5)、(A1, B3, R1-1, R2-2, R4-1)、(A1, B3, R1-1, R2-2, R4-2)、(A1, B3, R1-1, R2-2, R4-3)、(A1, B3, R1-1, R2-2, R4-4)、(A1, B3, R1-1, R2-2, R4-5)、(A1, B3, R1-1, R2-3, R4-1)、(A1, B3, R1-1, R2-3, R4-2)、(A1, B3, R1-1, R2-3, R4-3)、(A1, B3, R1-1, R2-3, R4-4)、(A1, B3, R1-1, R2-3, R4-5)、(A1, B3, R1-1, R2-4, R4-1)、(A1, B3, R1-1, R2-4, R4-2)、(A1, B3, R1-1, R2-4, R4-3)、(A1, B3, R1-1, R2-4, R4-4)、(A1, B3, R1-1, R2-4, R4-5)、(A1, B3, R1-1, R2-5, R4-1)、(A1, B3, R1-1, R2-5, R4-2)、(A1, B3, R1-1, R2-5, R4-3)、(A1, B3, R1-1, R2-5, R4-4)、(A1, B3, R1-1, R2-5, R4-5)、(A1, B3, R1-2, R2-1, R4-1)、(A1, B3, R1-2, R2-1, R4-2)、(A1, B3, R1-2, R2-1, R4-3)、(A1, B3, R1-2, R2-1, R4-4)、(A1, B3, R1-2, R2-1, R4-5)、(A1, B3, R1-2, R2-2, R4-1)、(A1, B3, R1-2, R2-2, R4-2)、(A1, B3, R1-2, R2-2, R4-3)、(A1, B3, R1-2, R2-2, R4-4)、(A1, B3, R1-2, R2-2, R4-5)、(A1, B3, R1-2, R2-3, R4-1)、(A1, B3, R1-2, R2-3, R4-2)、(A1, B3, R1-2, R2-3, R4-3)、(A1, B3, R1-2, R2-3, R4-4)、(A1, B3, R1-2, R2-3, R4-5)、(A1, B3, R1-2, R2-4, R4-1)、(A1, B3, R1-2, R2-4, R4-2)、(A1, B3, R1-2, R2-4, R4-3)、(A1, B3, R1-2, R2-4, R4-4)、(A1, B3, R1-2, R2-4, R4-5)、(A1, B3, R1-2, R2-5, R4-1)、(A1, B3, R1-2, R2-5, R4-2)、(A1, B3, R1-2, R2-5, R4-3)、(A1, B3, R1-2, R2-5, R4-4)、(A1, B3, R1-2, R2-5, R4-5)、(A1, B3, R1-3, R2-1, R4-1)、(A1, B3, R1-3, R2-1, R4-2)、(A1, B3, R1-3, R2-1, R4-3)、(A1, B3, R1-3, R2-1, R4-4)、(A1, B3, R1-3, R2-1, R4-5)、(A1, B3, R1-3, R2-2, R4-1)、(A1, B3, R1-3, R2-2, R4-2)、(A1, B3, R1-3, R2-2, R4-3)、(A1, B3, R1-3, R2-2, R4-4)、(A1, B3, R1-3, R2-2, R4-5)、(A1, B3, R1-3, R2-3, R4-1)、(A1, B3, R1-3, R2-3, R4-2)、(A1, B3, R1-3, R2-3, R4-3)、(A1, B3, R1-3, R2-3, R4-4)、(A1, B3, R1-3, R2-3, R4-5)、(A1, B3, R1-3, R2-4, R4-1)、(A1, B3, R1-3, R2-4, R4-2)、(A1, B3, R1-3, R2-4, R4-3)、(A1, B3, R1-3, R2-4, R4-4)、(A1, B3, R1-3, R2-4, R4-5)、(A1, B3, R1-3, R2-5, R4-1)、(A1, B3, R1-3, R2-5, R4-2)、(A1, B3, R1-3, R2-5, R4-3)、(A1, B3, R1-3, R2-5, R4-4)、(A1, B3, R1-3, R2-5, R4-5)、(A1, B4, R1-1, R2-1, R4-1)、(A1, B4, R1-1, R2-1, R4-2)、(A1, B4, R1-1, R2-1, R4-3)、(A1, B4, R1-1, R2-1, R4-4)、(A1, B4, R1-1, R2-1, R4-5)、(A1, B4, R1-1, R2-2, R4-1)、(A1, B4, R1-1, R2-2, R4-2)、(A1, B4, R1-1, R2-2, R4-3)、(A1, B4, R1-1, R2-2, R4-4)、(A1, B4, R1-1, R2-2, R4-5)、(A1, B4, R1-1, R2-3, R4-1)、(A1, B4, R1-1, R2-3, R4-2)、(A1, B4, R1-1, R2-3, R4-3)、(A1, B4, R1-1, R2-3, R4-4)、(A1, B4, R1-1, R2-3, R4-5)、(A1, B4, R1-1, R2-4, R4-1)、(A1, B4, R1-1, R2-4, R4-2)、(A1, B4, R1-1, R2-4, R4-3)、(A1, B4, R1-1, R2-4, R4-4)、(A1, B4, R1-1, R2-4, R4-5)、(A1, B4, R1-1, R2-5, R4-1)、(A1, B4, R1-1, R2-5, R4-2)、(A1, B4, R1-1, R2-5, R4-3)、(A1, B4, R1-1, R2-5, R4-4)、(A1, B4, R1-1, R2-5, R4-5)、(A1, B4, R1-2, R2-1, R4-1)、(A1, B4, R1-2, R2-1, R4-2)、(A1, B4, R1-2, R2-1, R4-3)、(A1, B4, R1-2, R2-1, R4-4)、(A1, B4, R1-2, R2-1, R4-5)、(A1, B4, R1-2, R2-2, R4-1)、(A1, B4, R1-2, R2-2, R4-2)、(A1, B4, R1-2, R2-2, R4-3)、(A1, B4, R1-2, R2-2, R4-4)、(A1, B4, R1-2, R2-2, R4-5)、(A1, B4, R1-2, R2-3, R4-1)、(A1, B4, R1-2, R2-3, R4-2)、(A1, B4, R1-2, R2-3, R4-3)、(A1, B4, R1-2, R2-3, R4-4)、(A1, B4, R1-2, R2-3, R4-5)、(A1, B4, R1-2, R2-4, R4-1)、(A1, B4, R1-2, R2-4, R4-2)、(A1, B4, R1-2, R2-4, R4-3)、(A1, B4, R1-2, R2-4, R4-4)、(A1, B4, R1-2, R2-4, R4-5)、(A1, B4, R1-2, R2-5, R4-1)、(A1, B4, R1-2, R2-5, R4-2)、(A1, B4, R1-2, R2-5, R4-3)、(A1, B4, R1-2, R2-5, R4-4)、(A1, B4, R1-2, R2-5, R4-5)、(A1, B4, R1-3, R2-1, R4-1)、(A1, B4, R1-3, R2-1, R4-2)、(A1, B4, R1-3, R2-1, R4-3)、(A1, B4, R1-3, R2-1, R4-4)、(A1, B4, R1-3, R2-1, R4-5)、(A1, B4, R1-3, R2-2, R4-1)、(A1, B4, R1-3, R2-2, R4-2)、(A1, B4, R1-3, R2-2, R4-3)、(A1, B4, R1-3, R2-2, R4-4)、(A1, B4, R1-3, R2-2, R4-5)、(A1, B4, R1-3, R2-3, R4-1)、(A1, B4, R1-3, R2-3, R4-2)、(A1, B4, R1-3, R2-3, R4-3)、(A1, B4, R1-3, R2-3, R4-4)、(A1, B4, R1-3, R2-3, R4-5)、(A1, B4, R1-3, R2-4, R4-1)、(A1, B4, R1-3, R2-4, R4-2)、(A1, B4, R1-3, R2-4, R4-3)、(A1, B4, R1-3, R2-4, R4-4)、(A1, B4, R1-3, R2-4, R4-5)、(A1, B4, R1-3, R2-5, R4-1)、(A1, B4, R1-3, R2-5, R4-2)、(A1, B4, R1-3, R2-5, R4-3)、(A1, B4, R1-3, R2-5, R4-4)、(A1, B4, R1-3, R2-5, R4-5)、(A1, B5, R1-1, R2-1, R4-1)、(A1, B5, R1-1, R2-1, R4-2)、(A1, B5, R1-1, R2-1, R4-3)、(A1, B5, R1-1, R2-1, R4-4)、(A1, B5, R1-1, R2-1, R4-5)、(A1, B5, R1-1, R2-2, R4-1)、(A1, B5, R1-1, R2-2, R4-2)、(A1, B5, R1-1, R2-2, R4-3)、(A1, B5, R1-1, R2-2, R4-4)、(A1, B5, R1-1, R2-2, R4-5)、(A1, B5, R1-1, R2-3, R4-1)、(A1, B5, R1-1, R2-3, R4-2)、(A1, B5, R1-1, R2-3, R4-3)、(A1, B5, R1-1, R2-3, R4-4)、(A1, B5, R1-1, R2-3, R4-5)、(A1, B5, R1-1, R2-4, R4-1)、(A1, B5, R1-1, R2-4, R4-2)、(A1, B5, R1-1, R2-4, R4-3)、(A1, B5, R1-1, R2-4, R4-4)、(A1, B5, R1-1, R2-4, R4-5)、(A1, B5, R1-1, R2-5, R4-1)、(A1, B5, R1-1, R2-5, R4-2)、(A1, B5, R1-1, R2-5, R4-3)、(A1, B5, R1-1, R2-5, R4-4)、(A1, B5, R1-1, R2-5, R4-5)、(A1, B5, R1-2, R2-1, R4-1)、(A1, B5, R1-2, R2-1, R4-2)、(A1, B5, R1-2, R2-1, R4-3)、(A1, B5, R1-2, R2-1, R4-4)、(A1, B5, R1-2, R2-1, R4-5)、(A1, B5, R1-2, R2-2, R4-1)、(A1, B5, R1-2, R2-2, R4-2)、(A1, B5, R1-2, R2-2, R4-3)、(A1, B5, R1-2, R2-2, R4-4)、(A1, B5, R1-2, R2-2, R4-5)、(A1, B5, R1-2, R2-3, R4-1)、(A1, B5, R1-2, R2-3, R4-2)、(A1, B5, R1-2, R2-3, R4-3)、(A1, B5, R1-2, R2-3, R4-4)、(A1, B5, R1-2, R2-3, R4-5)、(A1, B5, R1-2, R2-4, R4-1)、(A1, B5, R1-2, R2-4, R4-2)、(A1, B5, R1-2, R2-4, R4-3)、(A1, B5, R1-2, R2-4, R4-4)、(A1, B5, R1-2, R2-4, R4-5)、(A1, B5, R1-2, R2-5, R4-1)、(A1, B5, R1-2, R2-5, R4-2)、(A1, B5, R1-2, R2-5, R4-3)、(A1, B5, R1-2, R2-5, R4-4)、(A1, B5, R1-2, R2-5, R4-5)、(A1, B5, R1-3, R2-1, R4-1)、(A1, B5, R1-3, R2-1, R4-2)、(A1, B5, R1-3, R2-1, R4-3)、(A1, B5, R1-3, R2-1, R4-4)、(A1, B5, R1-3, R2-1, R4-5)、(A1, B5, R1-3, R2-2, R4-1)、(A1, B5, R1-3, R2-2, R4-2)、(A1, B5, R1-3, R2-2, R4-3)、(A1, B5, R1-3, R2-2, R4-4)、(A1, B5, R1-3, R2-2, R4-5)、(A1, B5, R1-3, R2-3, R4-1)、(A1, B5, R1-3, R2-3, R4-2)、(A1, B5, R1-3, R2-3, R4-3)、(A1, B5, R1-3, R2-3, R4-4)、(A1, B5, R1-3, R2-3, R4-5)、
(A1, B5, R1-3, R2-4, R4-1)、(A1, B5, R1-3, R2-4, R4-2)、(A1, B5, R1-3, R2-4, R4-3)、(A1, B5, R1-3, R2-4, R4-4)、(A1, B5, R1-3, R2-4, R4-5)、(A1, B5, R1-3, R2-5, R4-1)、(A1, B5, R1-3, R2-5, R4-2)、(A1, B5, R1-3, R2-5, R4-3)、(A1, B5, R1-3, R2-5, R4-4)、(A1, B5, R1-3, R2-5, R4-5)、(A1, B6, R1-1, R2-1, R4-1)、(A1, B6, R1-1, R2-1, R4-2)、(A1, B6, R1-1, R2-1, R4-3)、(A1, B6, R1-1, R2-1, R4-4)、(A1, B6, R1-1, R2-1, R4-5)、(A1, B6, R1-1, R2-2, R4-1)、(A1, B6, R1-1, R2-2, R4-2)、(A1, B6, R1-1, R2-2, R4-3)、(A1, B6, R1-1, R2-2, R4-4)、(A1, B6, R1-1, R2-2, R4-5)、(A1, B6, R1-1, R2-3, R4-1)、(A1, B6, R1-1, R2-3, R4-2)、(A1, B6, R1-1, R2-3, R4-3)、(A1, B6, R1-1, R2-3, R4-4)、(A1, B6, R1-1, R2-3, R4-5)、(A1, B6, R1-1, R2-4, R4-1)、(A1, B6, R1-1, R2-4, R4-2)、(A1, B6, R1-1, R2-4, R4-3)、(A1, B6, R1-1, R2-4, R4-4)、(A1, B6, R1-1, R2-4, R4-5)、(A1, B6, R1-1, R2-5, R4-1)、(A1, B6, R1-1, R2-5, R4-2)、(A1, B6, R1-1, R2-5, R4-3)、(A1, B6, R1-1, R2-5, R4-4)、(A1, B6, R1-1, R2-5, R4-5)、(A1, B6, R1-2, R2-1, R4-1)、(A1, B6, R1-2, R2-1, R4-2)、(A1, B6, R1-2, R2-1, R4-3)、(A1, B6, R1-2, R2-1, R4-4)、(A1, B6, R1-2, R2-1, R4-5)、(A1, B6, R1-2, R2-2, R4-1)、(A1, B6, R1-2, R2-2, R4-2)、(A1, B6, R1-2, R2-2, R4-3)、(A1, B6, R1-2, R2-2, R4-4)、(A1, B6, R1-2, R2-2, R4-5)、(A1, B6, R1-2, R2-3, R4-1)、(A1, B6, R1-2, R2-3, R4-2)、(A1, B6, R1-2, R2-3, R4-3)、(A1, B6, R1-2, R2-3, R4-4)、(A1, B6, R1-2, R2-3, R4-5)、(A1, B6, R1-2, R2-4, R4-1)、(A1, B6, R1-2, R2-4, R4-2)、(A1, B6, R1-2, R2-4, R4-3)、(A1, B6, R1-2, R2-4, R4-4)、(A1, B6, R1-2, R2-4, R4-5)、(A1, B6, R1-2, R2-5, R4-1)、(A1, B6, R1-2, R2-5, R4-2)、(A1, B6, R1-2, R2-5, R4-3)、(A1, B6, R1-2, R2-5, R4-4)、(A1, B6, R1-2, R2-5, R4-5)、(A1, B6, R1-3, R2-1, R4-1)、(A1, B6, R1-3, R2-1, R4-2)、(A1, B6, R1-3, R2-1, R4-3)、(A1, B6, R1-3, R2-1, R4-4)、(A1, B6, R1-3, R2-1, R4-5)、(A1, B6, R1-3, R2-2, R4-1)、(A1, B6, R1-3, R2-2, R4-2)、(A1, B6, R1-3, R2-2, R4-3)、(A1, B6, R1-3, R2-2, R4-4)、(A1, B6, R1-3, R2-2, R4-5)、(A1, B6, R1-3, R2-3, R4-1)、(A1, B6, R1-3, R2-3, R4-2)、(A1, B6, R1-3, R2-3, R4-3)、(A1, B6, R1-3, R2-3, R4-4)、(A1, B6, R1-3, R2-3, R4-5)、(A1, B6, R1-3, R2-4, R4-1)、(A1, B6, R1-3, R2-4, R4-2)、(A1, B6, R1-3, R2-4, R4-3)、(A1, B6, R1-3, R2-4, R4-4)、(A1, B6, R1-3, R2-4, R4-5)、(A1, B6, R1-3, R2-5, R4-1)、(A1, B6, R1-3, R2-5, R4-2)、(A1, B6, R1-3, R2-5, R4-3)、(A1, B6, R1-3, R2-5, R4-4)、(A1, B6, R1-3, R2-5, R4-5)、(A1, B7, R1-1, R2-1, R4-1)、(A1, B7, R1-1, R2-1, R4-2)、(A1, B7, R1-1, R2-1, R4-3)、(A1, B7, R1-1, R2-1, R4-4)、(A1, B7, R1-1, R2-1, R4-5)、(A1, B7, R1-1, R2-2, R4-1)、(A1, B7, R1-1, R2-2, R4-2)、(A1, B7, R1-1, R2-2, R4-3)、(A1, B7, R1-1, R2-2, R4-4)、(A1, B7, R1-1, R2-2, R4-5)、(A1, B7, R1-1, R2-3, R4-1)、(A1, B7, R1-1, R2-3, R4-2)、(A1, B7, R1-1, R2-3, R4-3)、(A1, B7, R1-1, R2-3, R4-4)、(A1, B7, R1-1, R2-3, R4-5)、(A1, B7, R1-1, R2-4, R4-1)、(A1, B7, R1-1, R2-4, R4-2)、(A1, B7, R1-1, R2-4, R4-3)、(A1, B7, R1-1, R2-4, R4-4)、(A1, B7, R1-1, R2-4, R4-5)、(A1, B7, R1-1, R2-5, R4-1)、(A1, B7, R1-1, R2-5, R4-2)、(A1, B7, R1-1, R2-5, R4-3)、(A1, B7, R1-1, R2-5, R4-4)、(A1, B7, R1-1, R2-5, R4-5)、(A1, B7, R1-2, R2-1, R4-1)、(A1, B7, R1-2, R2-1, R4-2)、(A1, B7, R1-2, R2-1, R4-3)、(A1, B7, R1-2, R2-1, R4-4)、(A1, B7, R1-2, R2-1, R4-5)、(A1, B7, R1-2, R2-2, R4-1)、(A1, B7, R1-2, R2-2, R4-2)、(A1, B7, R1-2, R2-2, R4-3)、(A1, B7, R1-2, R2-2, R4-4)、(A1, B7, R1-2, R2-2, R4-5)、(A1, B7, R1-2, R2-3, R4-1)、(A1, B7, R1-2, R2-3, R4-2)、(A1, B7, R1-2, R2-3, R4-3)、(A1, B7, R1-2, R2-3, R4-4)、(A1, B7, R1-2, R2-3, R4-5)、(A1, B7, R1-2, R2-4, R4-1)、(A1, B7, R1-2, R2-4, R4-2)、(A1, B7, R1-2, R2-4, R4-3)、(A1, B7, R1-2, R2-4, R4-4)、(A1, B7, R1-2, R2-4, R4-5)、(A1, B7, R1-2, R2-5, R4-1)、(A1, B7, R1-2, R2-5, R4-2)、(A1, B7, R1-2, R2-5, R4-3)、(A1, B7, R1-2, R2-5, R4-4)、(A1, B7, R1-2, R2-5, R4-5)、(A1, B7, R1-3, R2-1, R4-1)、(A1, B7, R1-3, R2-1, R4-2)、(A1, B7, R1-3, R2-1, R4-3)、(A1, B7, R1-3, R2-1, R4-4)、(A1, B7, R1-3, R2-1, R4-5)、(A1, B7, R1-3, R2-2, R4-1)、(A1, B7, R1-3, R2-2, R4-2)、(A1, B7, R1-3, R2-2, R4-3)、(A1, B7, R1-3, R2-2, R4-4)、(A1, B7, R1-3, R2-2, R4-5)、(A1, B7, R1-3, R2-3, R4-1)、(A1, B7, R1-3, R2-3, R4-2)、(A1, B7, R1-3, R2-3, R4-3)、(A1, B7, R1-3, R2-3, R4-4)、(A1, B7, R1-3, R2-3, R4-5)、(A1, B7, R1-3, R2-4, R4-1)、(A1, B7, R1-3, R2-4, R4-2)、(A1, B7, R1-3, R2-4, R4-3)、(A1, B7, R1-3, R2-4, R4-4)、(A1, B7, R1-3, R2-4, R4-5)、(A1, B7, R1-3, R2-5, R4-1)、(A1, B7, R1-3, R2-5, R4-2)、(A1, B7, R1-3, R2-5, R4-3)、(A1, B7, R1-3, R2-5, R4-4)、(A1, B7, R1-3, R2-5, R4-5)、(A1, B8, R1-1, R2-1, R4-1)、(A1, B8, R1-1, R2-1, R4-2)、(A1, B8, R1-1, R2-1, R4-3)、(A1, B8, R1-1, R2-1, R4-4)、(A1, B8, R1-1, R2-1, R4-5)、(A1, B8, R1-1, R2-2, R4-1)、(A1, B8, R1-1, R2-2, R4-2)、(A1, B8, R1-1, R2-2, R4-3)、(A1, B8, R1-1, R2-2, R4-4)、(A1, B8, R1-1, R2-2, R4-5)、(A1, B8, R1-1, R2-3, R4-1)、(A1, B8, R1-1, R2-3, R4-2)、(A1, B8, R1-1, R2-3, R4-3)、(A1, B8, R1-1, R2-3, R4-4)、(A1, B8, R1-1, R2-3, R4-5)、(A1, B8, R1-1, R2-4, R4-1)、(A1, B8, R1-1, R2-4, R4-2)、(A1, B8, R1-1, R2-4, R4-3)、(A1, B8, R1-1, R2-4, R4-4)、(A1, B8, R1-1, R2-4, R4-5)、(A1, B8, R1-1, R2-5, R4-1)、(A1, B8, R1-1, R2-5, R4-2)、(A1, B8, R1-1, R2-5, R4-3)、(A1, B8, R1-1, R2-5, R4-4)、(A1, B8, R1-1, R2-5, R4-5)、(A1, B8, R1-2, R2-1, R4-1)、(A1, B8, R1-2, R2-1, R4-2)、(A1, B8, R1-2, R2-1, R4-3)、(A1, B8, R1-2, R2-1, R4-4)、(A1, B8, R1-2, R2-1, R4-5)、(A1, B8, R1-2, R2-2, R4-1)、(A1, B8, R1-2, R2-2, R4-2)、(A1, B8, R1-2, R2-2, R4-3)、(A1, B8, R1-2, R2-2, R4-4)、(A1, B8, R1-2, R2-2, R4-5)、(A1, B8, R1-2, R2-3, R4-1)、(A1, B8, R1-2, R2-3, R4-2)、(A1, B8, R1-2, R2-3, R4-3)、(A1, B8, R1-2, R2-3, R4-4)、(A1, B8, R1-2, R2-3, R4-5)、(A1, B8, R1-2, R2-4, R4-1)、(A1, B8, R1-2, R2-4, R4-2)、(A1, B8, R1-2, R2-4, R4-3)、(A1, B8, R1-2, R2-4, R4-4)、(A1, B8, R1-2, R2-4, R4-5)、(A1, B8, R1-2, R2-5, R4-1)、(A1, B8, R1-2, R2-5, R4-2)、(A1, B8, R1-2, R2-5, R4-3)、(A1, B8, R1-2, R2-5, R4-4)、(A1, B8, R1-2, R2-5, R4-5)、(A1, B8, R1-3, R2-1, R4-1)、(A1, B8, R1-3, R2-1, R4-2)、(A1, B8, R1-3, R2-1, R4-3)、(A1, B8, R1-3, R2-1, R4-4)、(A1, B8, R1-3, R2-1, R4-5)、(A1, B8, R1-3, R2-2, R4-1)、(A1, B8, R1-3, R2-2, R4-2)、(A1, B8, R1-3, R2-2, R4-3)、(A1, B8, R1-3, R2-2, R4-4)、(A1, B8, R1-3, R2-2, R4-5)、(A1, B8, R1-3, R2-3, R4-1)、(A1, B8, R1-3, R2-3, R4-2)、(A1, B8, R1-3, R2-3, R4-3)、(A1, B8, R1-3, R2-3, R4-4)、(A1, B8, R1-3, R2-3, R4-5)、(A1, B8, R1-3, R2-4, R4-1)、(A1, B8, R1-3, R2-4, R4-2)、(A1, B8, R1-3, R2-4, R4-3)、(A1, B8, R1-3, R2-4, R4-4)、(A1, B8, R1-3, R2-4, R4-5)、(A1, B8, R1-3, R2-5, R4-1)、(A1, B8, R1-3, R2-5, R4-2)、(A1, B8, R1-3, R2-5, R4-3)、(A1, B8, R1-3, R2-5, R4-4)、(A1, B8, R1-3, R2-5, R4-5)、(A1, B9, R1-1, R2-1, R4-1)、(A1, B9, R1-1, R2-1, R4-2)、(A1, B9, R1-1, R2-1, R4-3)、(A1, B9, R1-1, R2-1, R4-4)、(A1, B9, R1-1, R2-1, R4-5)、(A1, B9, R1-1, R2-2, R4-1)、(A1, B9, R1-1, R2-2, R4-2)、(A1, B9, R1-1, R2-2, R4-3)、(A1, B9, R1-1, R2-2, R4-4)、(A1, B9, R1-1, R2-2, R4-5)、(A1, B9, R1-1, R2-3, R4-1)、(A1, B9, R1-1, R2-3, R4-2)、(A1, B9, R1-1, R2-3, R4-3)、(A1, B9, R1-1, R2-3, R4-4)、(A1, B9, R1-1, R2-3, R4-5)、(A1, B9, R1-1, R2-4, R4-1)、(A1, B9, R1-1, R2-4, R4-2)、(A1, B9, R1-1, R2-4, R4-3)、(A1, B9, R1-1, R2-4, R4-4)、(A1, B9, R1-1, R2-4, R4-5)、(A1, B9, R1-1, R2-5, R4-1)、(A1, B9, R1-1, R2-5, R4-2)、(A1, B9, R1-1, R2-5, R4-3)、(A1, B9, R1-1, R2-5, R4-4)、(A1, B9, R1-1, R2-5, R4-5)、(A1, B9, R1-2, R2-1, R4-1)、(A1, B9, R1-2, R2-1, R4-2)、(A1, B9, R1-2, R2-1, R4-3)、(A1, B9, R1-2, R2-1, R4-4)、(A1, B9, R1-2, R2-1, R4-5)、(A1, B9, R1-2, R2-2, R4-1)、(A1, B9, R1-2, R2-2, R4-2)、(A1, B9, R1-2, R2-2, R4-3)、(A1, B9, R1-2, R2-2, R4-4)、(A1, B9, R1-2, R2-2, R4-5)、(A1, B9, R1-2, R2-3, R4-1)、(A1, B9, R1-2, R2-3, R4-2)、(A1, B9, R1-2, R2-3, R4-3)、(A1, B9, R1-2, R2-3, R4-4)、(A1, B9, R1-2, R2-3, R4-5)、(A1, B9, R1-2, R2-4, R4-1)、(A1, B9, R1-2, R2-4, R4-2)、(A1, B9, R1-2, R2-4, R4-3)、(A1, B9, R1-2, R2-4, R4-4)、(A1, B9, R1-2, R2-4, R4-5)、(A1, B9, R1-2, R2-5, R4-1)、(A1, B9, R1-2, R2-5, R4-2)、(A1, B9, R1-2, R2-5, R4-3)、(A1, B9, R1-2, R2-5, R4-4)、(A1, B9, R1-2, R2-5, R4-5)、(A1, B9, R1-3, R2-1, R4-1)、(A1, B9, R1-3, R2-1, R4-2)、(A1, B9, R1-3, R2-1, R4-3)、(A1, B9, R1-3, R2-1, R4-4)、(A1, B9, R1-3, R2-1, R4-5)、(A1, B9, R1-3, R2-2, R4-1)、(A1, B9, R1-3, R2-2, R4-2)、(A1, B9, R1-3, R2-2, R4-3)、(A1, B9, R1-3, R2-2, R4-4)、(A1, B9, R1-3, R2-2, R4-5)、(A1, B9, R1-3, R2-3, R4-1)、(A1, B9, R1-3, R2-3, R4-2)、(A1, B9, R1-3, R2-3, R4-3)、(A1, B9, R1-3, R2-3, R4-4)、(A1, B9, R1-3, R2-3, R4-5)、(A1, B9, R1-3, R2-4, R4-1)、(A1, B9, R1-3, R2-4, R4-2)、(A1, B9, R1-3, R2-4, R4-3)、(A1, B9, R1-3, R2-4, R4-4)、(A1, B9, R1-3, R2-4, R4-5)、(A1, B9, R1-3, R2-5, R4-1)、(A1, B9, R1-3, R2-5, R4-2)、(A1, B9, R1-3, R2-5, R4-3)、(A1, B9, R1-3, R2-5, R4-4)、(A1, B9, R1-3, R2-5, R4-5)、(A1, B10, R1-1, R2-1, R4-1)、(A1, B10, R1-1, R2-1, R4-2)、(A1, B10, R1-1, R2-1, R4-3)、(A1, B10, R1-1, R2-1, R4-4)、(A1, B10, R1-1, R2-1, R4-5)、(A1, B10, R1-1, R2-2, R4-1)、(A1, B10, R1-1, R2-2, R4-2)、(A1, B10, R1-1, R2-2, R4-3)、(A1, B10, R1-1, R2-2, R4-4)、(A1, B10, R1-1, R2-2, R4-5)、(A1, B10, R1-1, R2-3, R4-1)、(A1, B10, R1-1, R2-3, R4-2)、(A1, B10, R1-1, R2-3, R4-3)、(A1, B10, R1-1, R2-3, R4-4)、(A1, B10, R1-1, R2-3, R4-5)、(A1, B10, R1-1, R2-4, R4-1)、(A1, B10, R1-1, R2-4, R4-2)、(A1, B10, R1-1, R2-4, R4-3)、(A1, B10, R1-1, R2-4, R4-4)、(A1, B10, R1-1, R2-4, R4-5)、(A1, B10, R1-1, R2-5, R4-1)、(A1, B10, R1-1, R2-5, R4-2)、(A1, B10, R1-1, R2-5, R4-3)、(A1, B10, R1-1, R2-5, R4-4)、(A1, B10, R1-1, R2-5, R4-5)、(A1, B10, R1-2, R2-1, R4-1)、(A1, B10, R1-2, R2-1, R4-2)、(A1, B10, R1-2, R2-1, R4-3)、(A1, B10, R1-2, R2-1, R4-4)、(A1, B10, R1-2, R2-1, R4-5)、(A1, B10, R1-2, R2-2, R4-1)、(A1, B10, R1-2, R2-2, R4-2)、(A1, B10, R1-2, R2-2, R4-3)、(A1, B10, R1-2, R2-2, R4-4)、(A1, B10, R1-2, R2-2, R4-5)、(A1, B10, R1-2, R2-3, R4-1)、(A1, B10, R1-2, R2-3, R4-2)、(A1, B10, R1-2, R2-3, R4-3)、(A1, B10, R1-2, R2-3, R4-4)、(A1, B10, R1-2, R2-3, R4-5)、(A1, B10, R1-2, R2-4, R4-1)、(A1, B10, R1-2, R2-4, R4-2)、(A1, B10, R1-2, R2-4, R4-3)、(A1, B10, R1-2, R2-4, R4-4)、(A1, B10, R1-2, R2-4, R4-5)、(A1, B10, R1-2, R2-5, R4-1)、(A1, B10, R1-2, R2-5, R4-2)、(A1, B10, R1-2, R2-5, R4-3)、(A1, B10, R1-2, R2-5, R4-4)、(A1, B10, R1-2, R2-5, R4-5)、(A1, B10, R1-3, R2-1, R4-1)、(A1, B10, R1-3, R2-1, R4-2)、(A1, B10, R1-3, R2-1, R4-3)、(A1, B10, R1-3, R2-1, R4
-4)、(A1, B10, R1-3, R2-1, R4-5)、(A1, B10, R1-3, R2-2, R4-1)、(A1, B10, R1-3, R2-2, R4-2)、(A1, B10, R1-3, R2-2, R4-3)、(A1, B10, R1-3, R2-2, R4-4)、(A1, B10, R1-3, R2-2, R4-5)、(A1, B10, R1-3, R2-3, R4-1)、(A1, B10, R1-3, R2-3, R4-2)、(A1, B10, R1-3, R2-3, R4-3)、(A1, B10, R1-3, R2-3, R4-4)、(A1, B10, R1-3, R2-3, R4-5)、(A1, B10, R1-3, R2-4, R4-1)、(A1, B10, R1-3, R2-4, R4-2)、(A1, B10, R1-3, R2-4, R4-3)、(A1, B10, R1-3, R2-4, R4-4)、(A1, B10, R1-3, R2-4, R4-5)、(A1, B10, R1-3, R2-5, R4-1)、(A1, B10, R1-3, R2-5, R4-2)、(A1, B10, R1-3, R2-5, R4-3)、(A1, B10, R1-3, R2-5, R4-4)、(A1, B10, R1-3, R2-5, R4-5)、(A2, B1, R1-1, R2-1, R4-1)、(A2, B1, R1-1, R2-1, R4-2)、(A2, B1, R1-1, R2-1, R4-3)、(A2, B1, R1-1, R2-1, R4-4)、(A2, B1, R1-1, R2-1, R4-5)、(A2, B1, R1-1, R2-2, R4-1)、(A2, B1, R1-1, R2-2, R4-2)、(A2, B1, R1-1, R2-2, R4-3)、(A2, B1, R1-1, R2-2, R4-4)、(A2, B1, R1-1, R2-2, R4-5)、(A2, B1, R1-1, R2-3, R4-1)、(A2, B1, R1-1, R2-3, R4-2)、(A2, B1, R1-1, R2-3, R4-3)、(A2, B1, R1-1, R2-3, R4-4)、(A2, B1, R1-1, R2-3, R4-5)、(A2, B1, R1-1, R2-4, R4-1)、(A2, B1, R1-1, R2-4, R4-2)、(A2, B1, R1-1, R2-4, R4-3)、(A2, B1, R1-1, R2-4, R4-4)、(A2, B1, R1-1, R2-4, R4-5)、(A2, B1, R1-1, R2-5, R4-1)、(A2, B1, R1-1, R2-5, R4-2)、(A2, B1, R1-1, R2-5, R4-3)、(A2, B1, R1-1, R2-5, R4-4)、(A2, B1, R1-1, R2-5, R4-5)、(A2, B1, R1-2, R2-1, R4-1)、(A2, B1, R1-2, R2-1, R4-2)、(A2, B1, R1-2, R2-1, R4-3)、(A2, B1, R1-2, R2-1, R4-4)、(A2, B1, R1-2, R2-1, R4-5)、(A2, B1, R1-2, R2-2, R4-1)、(A2, B1, R1-2, R2-2, R4-2)、(A2, B1, R1-2, R2-2, R4-3)、(A2, B1, R1-2, R2-2, R4-4)、(A2, B1, R1-2, R2-2, R4-5)、(A2, B1, R1-2, R2-3, R4-1)、(A2, B1, R1-2, R2-3, R4-2)、(A2, B1, R1-2, R2-3, R4-3)、(A2, B1, R1-2, R2-3, R4-4)、(A2, B1, R1-2, R2-3, R4-5)、(A2, B1, R1-2, R2-4, R4-1)、(A2, B1, R1-2, R2-4, R4-2)、(A2, B1, R1-2, R2-4, R4-3)、(A2, B1, R1-2, R2-4, R4-4)、(A2, B1, R1-2, R2-4, R4-5)、(A2, B1, R1-2, R2-5, R4-1)、(A2, B1, R1-2, R2-5, R4-2)、(A2, B1, R1-2, R2-5, R4-3)、(A2, B1, R1-2, R2-5, R4-4)、(A2, B1, R1-2, R2-5, R4-5)、(A2, B1, R1-3, R2-1, R4-1)、(A2, B1, R1-3, R2-1, R4-2)、(A2, B1, R1-3, R2-1, R4-3)、(A2, B1, R1-3, R2-1, R4-4)、(A2, B1, R1-3, R2-1, R4-5)、(A2, B1, R1-3, R2-2, R4-1)、(A2, B1, R1-3, R2-2, R4-2)、(A2, B1, R1-3, R2-2, R4-3)、(A2, B1, R1-3, R2-2, R4-4)、(A2, B1, R1-3, R2-2, R4-5)、(A2, B1, R1-3, R2-3, R4-1)、(A2, B1, R1-3, R2-3, R4-2)、(A2, B1, R1-3, R2-3, R4-3)、(A2, B1, R1-3, R2-3, R4-4)、(A2, B1, R1-3, R2-3, R4-5)、(A2, B1, R1-3, R2-4, R4-1)、(A2, B1, R1-3, R2-4, R4-2)、(A2, B1, R1-3, R2-4, R4-3)、(A2, B1, R1-3, R2-4, R4-4)、(A2, B1, R1-3, R2-4, R4-5)、(A2, B1, R1-3, R2-5, R4-1)、(A2, B1, R1-3, R2-5, R4-2)、(A2, B1, R1-3, R2-5, R4-3)、(A2, B1, R1-3, R2-5, R4-4)、(A2, B1, R1-3, R2-5, R4-5)、(A2, B2, R1-1, R2-1, R4-1)、(A2, B2, R1-1, R2-1, R4-2)、(A2, B2, R1-1, R2-1, R4-3)、(A2, B2, R1-1, R2-1, R4-4)、(A2, B2, R1-1, R2-1, R4-5)、(A2, B2, R1-1, R2-2, R4-1)、(A2, B2, R1-1, R2-2, R4-2)、(A2, B2, R1-1, R2-2, R4-3)、(A2, B2, R1-1, R2-2, R4-4)、(A2, B2, R1-1, R2-2, R4-5)、(A2, B2, R1-1, R2-3, R4-1)、(A2, B2, R1-1, R2-3, R4-2)、(A2, B2, R1-1, R2-3, R4-3)、(A2, B2, R1-1, R2-3, R4-4)、(A2, B2, R1-1, R2-3, R4-5)、(A2, B2, R1-1, R2-4, R4-1)、(A2, B2, R1-1, R2-4, R4-2)、(A2, B2, R1-1, R2-4, R4-3)、(A2, B2, R1-1, R2-4, R4-4)、(A2, B2, R1-1, R2-4, R4-5)、(A2, B2, R1-1, R2-5, R4-1)、(A2, B2, R1-1, R2-5, R4-2)、(A2, B2, R1-1, R2-5, R4-3)、(A2, B2, R1-1, R2-5, R4-4)、(A2, B2, R1-1, R2-5, R4-5)、(A2, B2, R1-2, R2-1, R4-1)、(A2, B2, R1-2, R2-1, R4-2)、(A2, B2, R1-2, R2-1, R4-3)、(A2, B2, R1-2, R2-1, R4-4)、(A2, B2, R1-2, R2-1, R4-5)、(A2, B2, R1-2, R2-2, R4-1)、(A2, B2, R1-2, R2-2, R4-2)、(A2, B2, R1-2, R2-2, R4-3)、(A2, B2, R1-2, R2-2, R4-4)、(A2, B2, R1-2, R2-2, R4-5)、(A2, B2, R1-2, R2-3, R4-1)、(A2, B2, R1-2, R2-3, R4-2)、(A2, B2, R1-2, R2-3, R4-3)、(A2, B2, R1-2, R2-3, R4-4)、(A2, B2, R1-2, R2-3, R4-5)、(A2, B2, R1-2, R2-4, R4-1)、(A2, B2, R1-2, R2-4, R4-2)、(A2, B2, R1-2, R2-4, R4-3)、(A2, B2, R1-2, R2-4, R4-4)、(A2, B2, R1-2, R2-4, R4-5)、(A2, B2, R1-2, R2-5, R4-1)、(A2, B2, R1-2, R2-5, R4-2)、(A2, B2, R1-2, R2-5, R4-3)、(A2, B2, R1-2, R2-5, R4-4)、(A2, B2, R1-2, R2-5, R4-5)、(A2, B2, R1-3, R2-1, R4-1)、(A2, B2, R1-3, R2-1, R4-2)、(A2, B2, R1-3, R2-1, R4-3)、(A2, B2, R1-3, R2-1, R4-4)、(A2, B2, R1-3, R2-1, R4-5)、(A2, B2, R1-3, R2-2, R4-1)、(A2, B2, R1-3, R2-2, R4-2)、(A2, B2, R1-3, R2-2, R4-3)、(A2, B2, R1-3, R2-2, R4-4)、(A2, B2, R1-3, R2-2, R4-5)、(A2, B2, R1-3, R2-3, R4-1)、(A2, B2, R1-3, R2-3, R4-2)、(A2, B2, R1-3, R2-3, R4-3)、(A2, B2, R1-3, R2-3, R4-4)、(A2, B2, R1-3, R2-3, R4-5)、(A2, B2, R1-3, R2-4, R4-1)、(A2, B2, R1-3, R2-4, R4-2)、(A2, B2, R1-3, R2-4, R4-3)、(A2, B2, R1-3, R2-4, R4-4)、(A2, B2, R1-3, R2-4, R4-5)、(A2, B2, R1-3, R2-5, R4-1)、(A2, B2, R1-3, R2-5, R4-2)、(A2, B2, R1-3, R2-5, R4-3)、(A2, B2, R1-3, R2-5, R4-4)、(A2, B2, R1-3, R2-5, R4-5)、(A2, B3, R1-1, R2-1, R4-1)、(A2, B3, R1-1, R2-1, R4-2)、(A2, B3, R1-1, R2-1, R4-3)、(A2, B3, R1-1, R2-1, R4-4)、(A2, B3, R1-1, R2-1, R4-5)、(A2, B3, R1-1, R2-2, R4-1)、(A2, B3, R1-1, R2-2, R4-2)、(A2, B3, R1-1, R2-2, R4-3)、(A2, B3, R1-1, R2-2, R4-4)、(A2, B3, R1-1, R2-2, R4-5)、(A2, B3, R1-1, R2-3, R4-1)、(A2, B3, R1-1, R2-3, R4-2)、(A2, B3, R1-1, R2-3, R4-3)、(A2, B3, R1-1, R2-3, R4-4)、(A2, B3, R1-1, R2-3, R4-5)、(A2, B3, R1-1, R2-4, R4-1)、(A2, B3, R1-1, R2-4, R4-2)、(A2, B3, R1-1, R2-4, R4-3)、(A2, B3, R1-1, R2-4, R4-4)、(A2, B3, R1-1, R2-4, R4-5)、(A2, B3, R1-1, R2-5, R4-1)、(A2, B3, R1-1, R2-5, R4-2)、(A2, B3, R1-1, R2-5, R4-3)、(A2, B3, R1-1, R2-5, R4-4)、(A2, B3, R1-1, R2-5, R4-5)、(A2, B3, R1-2, R2-1, R4-1)、(A2, B3, R1-2, R2-1, R4-2)、(A2, B3, R1-2, R2-1, R4-3)、(A2, B3, R1-2, R2-1, R4-4)、(A2, B3, R1-2, R2-1, R4-5)、(A2, B3, R1-2, R2-2, R4-1)、(A2, B3, R1-2, R2-2, R4-2)、(A2, B3, R1-2, R2-2, R4-3)、(A2, B3, R1-2, R2-2, R4-4)、(A2, B3, R1-2, R2-2, R4-5)、(A2, B3, R1-2, R2-3, R4-1)、(A2, B3, R1-2, R2-3, R4-2)、(A2, B3, R1-2, R2-3, R4-3)、(A2, B3, R1-2, R2-3, R4-4)、(A2, B3, R1-2, R2-3, R4-5)、(A2, B3, R1-2, R2-4, R4-1)、(A2, B3, R1-2, R2-4, R4-2)、(A2, B3, R1-2, R2-4, R4-3)、(A2, B3, R1-2, R2-4, R4-4)、(A2, B3, R1-2, R2-4, R4-5)、(A2, B3, R1-2, R2-5, R4-1)、(A2, B3, R1-2, R2-5, R4-2)、(A2, B3, R1-2, R2-5, R4-3)、(A2, B3, R1-2, R2-5, R4-4)、(A2, B3, R1-2, R2-5, R4-5)、(A2, B3, R1-3, R2-1, R4-1)、(A2, B3, R1-3, R2-1, R4-2)、(A2, B3, R1-3, R2-1, R4-3)、(A2, B3, R1-3, R2-1, R4-4)、(A2, B3, R1-3, R2-1, R4-5)、(A2, B3, R1-3, R2-2, R4-1)、(A2, B3, R1-3, R2-2, R4-2)、(A2, B3, R1-3, R2-2, R4-3)、(A2, B3, R1-3, R2-2, R4-4)、(A2, B3, R1-3, R2-2, R4-5)、(A2, B3, R1-3, R2-3, R4-1)、(A2, B3, R1-3, R2-3, R4-2)、(A2, B3, R1-3, R2-3, R4-3)、(A2, B3, R1-3, R2-3, R4-4)、(A2, B3, R1-3, R2-3, R4-5)、(A2, B3, R1-3, R2-4, R4-1)、(A2, B3, R1-3, R2-4, R4-2)、(A2, B3, R1-3, R2-4, R4-3)、(A2, B3, R1-3, R2-4, R4-4)、(A2, B3, R1-3, R2-4, R4-5)、(A2, B3, R1-3, R2-5, R4-1)、(A2, B3, R1-3, R2-5, R4-2)、(A2, B3, R1-3, R2-5, R4-3)、(A2, B3, R1-3, R2-5, R4-4)、(A2, B3, R1-3, R2-5, R4-5)、(A2, B4, R1-1, R2-1, R4-1)、(A2, B4, R1-1, R2-1, R4-2)、(A2, B4, R1-1, R2-1, R4-3)、(A2, B4, R1-1, R2-1, R4-4)、(A2, B4, R1-1, R2-1, R4-5)、(A2, B4, R1-1, R2-2, R4-1)、(A2, B4, R1-1, R2-2, R4-2)、(A2, B4, R1-1, R2-2, R4-3)、(A2, B4, R1-1, R2-2, R4-4)、(A2, B4, R1-1, R2-2, R4-5)、(A2, B4, R1-1, R2-3, R4-1)、(A2, B4, R1-1, R2-3, R4-2)、(A2, B4, R1-1, R2-3, R4-3)、(A2, B4, R1-1, R2-3, R4-4)、(A2, B4, R1-1, R2-3, R4-5)、(A2, B4, R1-1, R2-4, R4-1)、(A2, B4, R1-1, R2-4, R4-2)、(A2, B4, R1-1, R2-4, R4-3)、(A2, B4, R1-1, R2-4, R4-4)、(A2, B4, R1-1, R2-4, R4-5)、(A2, B4, R1-1, R2-5, R4-1)、(A2, B4, R1-1, R2-5, R4-2)、(A2, B4, R1-1, R2-5, R4-3)、(A2, B4, R1-1, R2-5, R4-4)、(A2, B4, R1-1, R2-5, R4-5)、(A2, B4, R1-2, R2-1, R4-1)、(A2, B4, R1-2, R2-1, R4-2)、(A2, B4, R1-2, R2-1, R4-3)、(A2, B4, R1-2, R2-1, R4-4)、(A2, B4, R1-2, R2-1, R4-5)、(A2, B4, R1-2, R2-2, R4-1)、(A2, B4, R1-2, R2-2, R4-2)、(A2, B4, R1-2, R2-2, R4-3)、(A2, B4, R1-2, R2-2, R4-4)、(A2, B4, R1-2, R2-2, R4-5)、(A2, B4, R1-2, R2-3, R4-1)、(A2, B4, R1-2, R2-3, R4-2)、(A2, B4, R1-2, R2-3, R4-3)、(A2, B4, R1-2, R2-3, R4-4)、(A2, B4, R1-2, R2-3, R4-5)、(A2, B4, R1-2, R2-4, R4-1)、(A2, B4, R1-2, R2-4, R4-2)、(A2, B4, R1-2, R2-4, R4-3)、(A2, B4, R1-2, R2-4, R4-4)、(A2, B4, R1-2, R2-4, R4-5)、(A2, B4, R1-2, R2-5, R4-1)、(A2, B4, R1-2, R2-5, R4-2)、(A2, B4, R1-2, R2-5, R4-3)、(A2, B4, R1-2, R2-5, R4-4)、(A2, B4, R1-2, R2-5, R4-5)、(A2, B4, R1-3, R2-1, R4-1)、(A2, B4, R1-3, R2-1, R4-2)、(A2, B4, R1-3, R2-1, R4-3)、(A2, B4, R1-3, R2-1, R4-4)、(A2, B4, R1-3, R2-1, R4-5)、(A2, B4, R1-3, R2-2, R4-1)、(A2, B4, R1-3, R2-2, R4-2)、(A2, B4, R1-3, R2-2, R4-3)、(A2, B4, R1-3, R2-2, R4-4)、(A2, B4, R1-3, R2-2, R4-5)、(A2, B4, R1-3, R2-3, R4-1)、(A2, B4, R1-3, R2-3, R4-2)、(A2, B4, R1-3, R2-3, R4-3)、(A2, B4, R1-3, R2-3, R4-4)、(A2, B4, R1-3, R2-3, R4-5)、(A2, B4, R1-3, R2-4, R4-1)、(A2, B4, R1-3, R2-4, R4-2)、(A2, B4, R1-3, R2-4, R4-3)、(A2, B4, R1-3, R2-4, R4-4)、(A2, B4, R1-3, R2-4, R4-5)、(A2, B4, R1-3, R2-5, R4-1)、(A2, B4, R1-3, R2-5, R4-2)、(A2, B4, R1-3, R2-5, R4-3)、(A2, B4, R1-3, R2-5, R4-4)、(A2, B4, R1-3, R2-5, R4-5)、(A2, B5, R1-1, R2-1, R4-1)、(A2, B5, R1-1, R2-1, R4-2)、(A2, B5, R1-1, R2-1, R4-3)、(A2, B5, R1-1, R2-1, R4-4)、(A2, B5, R1-1, R2-1, R4-5)、(A2, B5, R1-1, R2-2, R4-1)、(A2, B5, R1-1, R2-2, R4-2)、(A2, B5, R1-1, R2-2, R4-3)、(A2, B5, R1-1, R2-2, R4-4)、(A2, B5, R1-1, R2-2, R4-5)、(A2, B5, R1-1, R2-3, R4-1)、(A2, B5, R1-1, R2-3, R4-2)、(A2, B5, R1-1, R2-3, R4-3)、(A2, B5, R1-1, R2-3, R4-4)、(A2, B5, R1-1, R2-3, R4-5)、(A2, B5, R1-1, R2-4, R4-1)、(A2, B5, R1-1, R2-4, R4-2)、(A2, B5, R1-1, R2-4, R4-3)、(A2, B5, R1-1, R2-4, R4-4)、(A2, B5, R1-1, R2-4, R4-5)、(A2, B5, R1-1, R2-5, R4-1)、(A2, B5, R1-1, R2-5, R4-2)、(A2, B5, R1-1, R2-5, R4-3)、(A2, B5, R1-1, R2-5, R4-4)、(A2, B5, R1-1, R2-5, R4-5)、(A2, B5, R1-2, R2-1, R4-1)、(A2, B5, R1-2, R2-1, R4-2)、(A2, B5, R1-2, R2-1, R4-3)、(A2, B5, R1-2, R2-1, R4-4)、(A2, B5, R1-2, R2-1, R4-5)、(A2, B5, R1-2, R2-2, R4-1)、(A2, B5, R1-2, R2-2, R4-2)、(A2, B5, R1-2, R2-2, R4-3)、(A2, B5, R1-2, R2-2, R4-4)、(A2, B5, R1-2, R2-2, R4-5)、(A2, B5, R1-2, R2-3, R4-1)、(A2, B5, R1-2, R2-3, R4-2)、(A2, B5, R1-2, R2-3, R4-3)、(A2, B5, R1-2, R2-3, R4-4)、(A2, B5, R1-2, R2-3, R4-5)、(A2, B5, R1-2, R2-4, R4-1)、(A2, B5, R1-2, R2-4, R4-2)、(A2, B5, R1-2, R2-4, R4-3)、(A2, B5, R1-2, R2-4, R4
-4)、(A2, B5, R1-2, R2-4, R4-5)、(A2, B5, R1-2, R2-5, R4-1)、(A2, B5, R1-2, R2-5, R4-2)、(A2, B5, R1-2, R2-5, R4-3)、(A2, B5, R1-2, R2-5, R4-4)、(A2, B5, R1-2, R2-5, R4-5)、(A2, B5, R1-3, R2-1, R4-1)、(A2, B5, R1-3, R2-1, R4-2)、(A2, B5, R1-3, R2-1, R4-3)、(A2, B5, R1-3, R2-1, R4-4)、(A2, B5, R1-3, R2-1, R4-5)、(A2, B5, R1-3, R2-2, R4-1)、(A2, B5, R1-3, R2-2, R4-2)、(A2, B5, R1-3, R2-2, R4-3)、(A2, B5, R1-3, R2-2, R4-4)、(A2, B5, R1-3, R2-2, R4-5)、(A2, B5, R1-3, R2-3, R4-1)、(A2, B5, R1-3, R2-3, R4-2)、(A2, B5, R1-3, R2-3, R4-3)、(A2, B5, R1-3, R2-3, R4-4)、(A2, B5, R1-3, R2-3, R4-5)、(A2, B5, R1-3, R2-4, R4-1)、(A2, B5, R1-3, R2-4, R4-2)、(A2, B5, R1-3, R2-4, R4-3)、(A2, B5, R1-3, R2-4, R4-4)、(A2, B5, R1-3, R2-4, R4-5)、(A2, B5, R1-3, R2-5, R4-1)、(A2, B5, R1-3, R2-5, R4-2)、(A2, B5, R1-3, R2-5, R4-3)、(A2, B5, R1-3, R2-5, R4-4)、(A2, B5, R1-3, R2-5, R4-5)、(A2, B6, R1-1, R2-1, R4-1)、(A2, B6, R1-1, R2-1, R4-2)、(A2, B6, R1-1, R2-1, R4-3)、(A2, B6, R1-1, R2-1, R4-4)、(A2, B6, R1-1, R2-1, R4-5)、(A2, B6, R1-1, R2-2, R4-1)、(A2, B6, R1-1, R2-2, R4-2)、(A2, B6, R1-1, R2-2, R4-3)、(A2, B6, R1-1, R2-2, R4-4)、(A2, B6, R1-1, R2-2, R4-5)、(A2, B6, R1-1, R2-3, R4-1)、(A2, B6, R1-1, R2-3, R4-2)、(A2, B6, R1-1, R2-3, R4-3)、(A2, B6, R1-1, R2-3, R4-4)、(A2, B6, R1-1, R2-3, R4-5)、(A2, B6, R1-1, R2-4, R4-1)、(A2, B6, R1-1, R2-4, R4-2)、(A2, B6, R1-1, R2-4, R4-3)、(A2, B6, R1-1, R2-4, R4-4)、(A2, B6, R1-1, R2-4, R4-5)、(A2, B6, R1-1, R2-5, R4-1)、(A2, B6, R1-1, R2-5, R4-2)、(A2, B6, R1-1, R2-5, R4-3)、(A2, B6, R1-1, R2-5, R4-4)、(A2, B6, R1-1, R2-5, R4-5)、(A2, B6, R1-2, R2-1, R4-1)、(A2, B6, R1-2, R2-1, R4-2)、(A2, B6, R1-2, R2-1, R4-3)、(A2, B6, R1-2, R2-1, R4-4)、(A2, B6, R1-2, R2-1, R4-5)、(A2, B6, R1-2, R2-2, R4-1)、(A2, B6, R1-2, R2-2, R4-2)、(A2, B6, R1-2, R2-2, R4-3)、(A2, B6, R1-2, R2-2, R4-4)、(A2, B6, R1-2, R2-2, R4-5)、(A2, B6, R1-2, R2-3, R4-1)、(A2, B6, R1-2, R2-3, R4-2)、(A2, B6, R1-2, R2-3, R4-3)、(A2, B6, R1-2, R2-3, R4-4)、(A2, B6, R1-2, R2-3, R4-5)、(A2, B6, R1-2, R2-4, R4-1)、(A2, B6, R1-2, R2-4, R4-2)、(A2, B6, R1-2, R2-4, R4-3)、(A2, B6, R1-2, R2-4, R4-4)、(A2, B6, R1-2, R2-4, R4-5)、(A2, B6, R1-2, R2-5, R4-1)、(A2, B6, R1-2, R2-5, R4-2)、(A2, B6, R1-2, R2-5, R4-3)、(A2, B6, R1-2, R2-5, R4-4)、(A2, B6, R1-2, R2-5, R4-5)、(A2, B6, R1-3, R2-1, R4-1)、(A2, B6, R1-3, R2-1, R4-2)、(A2, B6, R1-3, R2-1, R4-3)、(A2, B6, R1-3, R2-1, R4-4)、(A2, B6, R1-3, R2-1, R4-5)、(A2, B6, R1-3, R2-2, R4-1)、(A2, B6, R1-3, R2-2, R4-2)、(A2, B6, R1-3, R2-2, R4-3)、(A2, B6, R1-3, R2-2, R4-4)、(A2, B6, R1-3, R2-2, R4-5)、(A2, B6, R1-3, R2-3, R4-1)、(A2, B6, R1-3, R2-3, R4-2)、(A2, B6, R1-3, R2-3, R4-3)、(A2, B6, R1-3, R2-3, R4-4)、(A2, B6, R1-3, R2-3, R4-5)、(A2, B6, R1-3, R2-4, R4-1)、(A2, B6, R1-3, R2-4, R4-2)、(A2, B6, R1-3, R2-4, R4-3)、(A2, B6, R1-3, R2-4, R4-4)、(A2, B6, R1-3, R2-4, R4-5)、(A2, B6, R1-3, R2-5, R4-1)、(A2, B6, R1-3, R2-5, R4-2)、(A2, B6, R1-3, R2-5, R4-3)、(A2, B6, R1-3, R2-5, R4-4)、(A2, B6, R1-3, R2-5, R4-5)、(A2, B7, R1-1, R2-1, R4-1)、(A2, B7, R1-1, R2-1, R4-2)、(A2, B7, R1-1, R2-1, R4-3)、(A2, B7, R1-1, R2-1, R4-4)、(A2, B7, R1-1, R2-1, R4-5)、(A2, B7, R1-1, R2-2, R4-1)、(A2, B7, R1-1, R2-2, R4-2)、(A2, B7, R1-1, R2-2, R4-3)、(A2, B7, R1-1, R2-2, R4-4)、(A2, B7, R1-1, R2-2, R4-5)、(A2, B7, R1-1, R2-3, R4-1)、(A2, B7, R1-1, R2-3, R4-2)、(A2, B7, R1-1, R2-3, R4-3)、(A2, B7, R1-1, R2-3, R4-4)、(A2, B7, R1-1, R2-3, R4-5)、(A2, B7, R1-1, R2-4, R4-1)、(A2, B7, R1-1, R2-4, R4-2)、(A2, B7, R1-1, R2-4, R4-3)、(A2, B7, R1-1, R2-4, R4-4)、(A2, B7, R1-1, R2-4, R4-5)、(A2, B7, R1-1, R2-5, R4-1)、(A2, B7, R1-1, R2-5, R4-2)、(A2, B7, R1-1, R2-5, R4-3)、(A2, B7, R1-1, R2-5, R4-4)、(A2, B7, R1-1, R2-5, R4-5)、(A2, B7, R1-2, R2-1, R4-1)、(A2, B7, R1-2, R2-1, R4-2)、(A2, B7, R1-2, R2-1, R4-3)、(A2, B7, R1-2, R2-1, R4-4)、(A2, B7, R1-2, R2-1, R4-5)、(A2, B7, R1-2, R2-2, R4-1)、(A2, B7, R1-2, R2-2, R4-2)、(A2, B7, R1-2, R2-2, R4-3)、(A2, B7, R1-2, R2-2, R4-4)、(A2, B7, R1-2, R2-2, R4-5)、(A2, B7, R1-2, R2-3, R4-1)、(A2, B7, R1-2, R2-3, R4-2)、(A2, B7, R1-2, R2-3, R4-3)、(A2, B7, R1-2, R2-3, R4-4)、(A2, B7, R1-2, R2-3, R4-5)、(A2, B7, R1-2, R2-4, R4-1)、(A2, B7, R1-2, R2-4, R4-2)、(A2, B7, R1-2, R2-4, R4-3)、(A2, B7, R1-2, R2-4, R4-4)、(A2, B7, R1-2, R2-4, R4-5)、(A2, B7, R1-2, R2-5, R4-1)、(A2, B7, R1-2, R2-5, R4-2)、(A2, B7, R1-2, R2-5, R4-3)、(A2, B7, R1-2, R2-5, R4-4)、(A2, B7, R1-2, R2-5, R4-5)、(A2, B7, R1-3, R2-1, R4-1)、(A2, B7, R1-3, R2-1, R4-2)、(A2, B7, R1-3, R2-1, R4-3)、(A2, B7, R1-3, R2-1, R4-4)、(A2, B7, R1-3, R2-1, R4-5)、(A2, B7, R1-3, R2-2, R4-1)、(A2, B7, R1-3, R2-2, R4-2)、(A2, B7, R1-3, R2-2, R4-3)、(A2, B7, R1-3, R2-2, R4-4)、(A2, B7, R1-3, R2-2, R4-5)、(A2, B7, R1-3, R2-3, R4-1)、(A2, B7, R1-3, R2-3, R4-2)、(A2, B7, R1-3, R2-3, R4-3)、(A2, B7, R1-3, R2-3, R4-4)、(A2, B7, R1-3, R2-3, R4-5)、(A2, B7, R1-3, R2-4, R4-1)、(A2, B7, R1-3, R2-4, R4-2)、(A2, B7, R1-3, R2-4, R4-3)、(A2, B7, R1-3, R2-4, R4-4)、(A2, B7, R1-3, R2-4, R4-5)、(A2, B7, R1-3, R2-5, R4-1)、(A2, B7, R1-3, R2-5, R4-2)、(A2, B7, R1-3, R2-5, R4-3)、(A2, B7, R1-3, R2-5, R4-4)、(A2, B7, R1-3, R2-5, R4-5)、(A2, B8, R1-1, R2-1, R4-1)、(A2, B8, R1-1, R2-1, R4-2)、(A2, B8, R1-1, R2-1, R4-3)、(A2, B8, R1-1, R2-1, R4-4)、(A2, B8, R1-1, R2-1, R4-5)、(A2, B8, R1-1, R2-2, R4-1)、(A2, B8, R1-1, R2-2, R4-2)、(A2, B8, R1-1, R2-2, R4-3)、(A2, B8, R1-1, R2-2, R4-4)、(A2, B8, R1-1, R2-2, R4-5)、(A2, B8, R1-1, R2-3, R4-1)、(A2, B8, R1-1, R2-3, R4-2)、(A2, B8, R1-1, R2-3, R4-3)、(A2, B8, R1-1, R2-3, R4-4)、(A2, B8, R1-1, R2-3, R4-5)、(A2, B8, R1-1, R2-4, R4-1)、(A2, B8, R1-1, R2-4, R4-2)、(A2, B8, R1-1, R2-4, R4-3)、(A2, B8, R1-1, R2-4, R4-4)、(A2, B8, R1-1, R2-4, R4-5)、(A2, B8, R1-1, R2-5, R4-1)、(A2, B8, R1-1, R2-5, R4-2)、(A2, B8, R1-1, R2-5, R4-3)、(A2, B8, R1-1, R2-5, R4-4)、(A2, B8, R1-1, R2-5, R4-5)、(A2, B8, R1-2, R2-1, R4-1)、(A2, B8, R1-2, R2-1, R4-2)、(A2, B8, R1-2, R2-1, R4-3)、(A2, B8, R1-2, R2-1, R4-4)、(A2, B8, R1-2, R2-1, R4-5)、(A2, B8, R1-2, R2-2, R4-1)、(A2, B8, R1-2, R2-2, R4-2)、(A2, B8, R1-2, R2-2, R4-3)、(A2, B8, R1-2, R2-2, R4-4)、(A2, B8, R1-2, R2-2, R4-5)、(A2, B8, R1-2, R2-3, R4-1)、(A2, B8, R1-2, R2-3, R4-2)、(A2, B8, R1-2, R2-3, R4-3)、(A2, B8, R1-2, R2-3, R4-4)、(A2, B8, R1-2, R2-3, R4-5)、(A2, B8, R1-2, R2-4, R4-1)、(A2, B8, R1-2, R2-4, R4-2)、(A2, B8, R1-2, R2-4, R4-3)、(A2, B8, R1-2, R2-4, R4-4)、(A2, B8, R1-2, R2-4, R4-5)、(A2, B8, R1-2, R2-5, R4-1)、(A2, B8, R1-2, R2-5, R4-2)、(A2, B8, R1-2, R2-5, R4-3)、(A2, B8, R1-2, R2-5, R4-4)、(A2, B8, R1-2, R2-5, R4-5)、(A2, B8, R1-3, R2-1, R4-1)、(A2, B8, R1-3, R2-1, R4-2)、(A2, B8, R1-3, R2-1, R4-3)、(A2, B8, R1-3, R2-1, R4-4)、(A2, B8, R1-3, R2-1, R4-5)、(A2, B8, R1-3, R2-2, R4-1)、(A2, B8, R1-3, R2-2, R4-2)、(A2, B8, R1-3, R2-2, R4-3)、(A2, B8, R1-3, R2-2, R4-4)、(A2, B8, R1-3, R2-2, R4-5)、(A2, B8, R1-3, R2-3, R4-1)、(A2, B8, R1-3, R2-3, R4-2)、(A2, B8, R1-3, R2-3, R4-3)、(A2, B8, R1-3, R2-3, R4-4)、(A2, B8, R1-3, R2-3, R4-5)、(A2, B8, R1-3, R2-4, R4-1)、(A2, B8, R1-3, R2-4, R4-2)、(A2, B8, R1-3, R2-4, R4-3)、(A2, B8, R1-3, R2-4, R4-4)、(A2, B8, R1-3, R2-4, R4-5)、(A2, B8, R1-3, R2-5, R4-1)、(A2, B8, R1-3, R2-5, R4-2)、(A2, B8, R1-3, R2-5, R4-3)、(A2, B8, R1-3, R2-5, R4-4)、(A2, B8, R1-3, R2-5, R4-5)、(A2, B9, R1-1, R2-1, R4-1)、(A2, B9, R1-1, R2-1, R4-2)、(A2, B9, R1-1, R2-1, R4-3)、(A2, B9, R1-1, R2-1, R4-4)、(A2, B9, R1-1, R2-1, R4-5)、(A2, B9, R1-1, R2-2, R4-1)、(A2, B9, R1-1, R2-2, R4-2)、(A2, B9, R1-1, R2-2, R4-3)、(A2, B9, R1-1, R2-2, R4-4)、(A2, B9, R1-1, R2-2, R4-5)、(A2, B9, R1-1, R2-3, R4-1)、(A2, B9, R1-1, R2-3, R4-2)、(A2, B9, R1-1, R2-3, R4-3)、(A2, B9, R1-1, R2-3, R4-4)、(A2, B9, R1-1, R2-3, R4-5)、(A2, B9, R1-1, R2-4, R4-1)、(A2, B9, R1-1, R2-4, R4-2)、(A2, B9, R1-1, R2-4, R4-3)、(A2, B9, R1-1, R2-4, R4-4)、(A2, B9, R1-1, R2-4, R4-5)、(A2, B9, R1-1, R2-5, R4-1)、(A2, B9, R1-1, R2-5, R4-2)、(A2, B9, R1-1, R2-5, R4-3)、(A2, B9, R1-1, R2-5, R4-4)、(A2, B9, R1-1, R2-5, R4-5)、(A2, B9, R1-2, R2-1, R4-1)、(A2, B9, R1-2, R2-1, R4-2)、(A2, B9, R1-2, R2-1, R4-3)、(A2, B9, R1-2, R2-1, R4-4)、(A2, B9, R1-2, R2-1, R4-5)、(A2, B9, R1-2, R2-2, R4-1)、(A2, B9, R1-2, R2-2, R4-2)、(A2, B9, R1-2, R2-2, R4-3)、(A2, B9, R1-2, R2-2, R4-4)、(A2, B9, R1-2, R2-2, R4-5)、(A2, B9, R1-2, R2-3, R4-1)、(A2, B9, R1-2, R2-3, R4-2)、(A2, B9, R1-2, R2-3, R4-3)、(A2, B9, R1-2, R2-3, R4-4)、(A2, B9, R1-2, R2-3, R4-5)、(A2, B9, R1-2, R2-4, R4-1)、(A2, B9, R1-2, R2-4, R4-2)、(A2, B9, R1-2, R2-4, R4-3)、(A2, B9, R1-2, R2-4, R4-4)、(A2, B9, R1-2, R2-4, R4-5)、(A2, B9, R1-2, R2-5, R4-1)、(A2, B9, R1-2, R2-5, R4-2)、(A2, B9, R1-2, R2-5, R4-3)、(A2, B9, R1-2, R2-5, R4-4)、(A2, B9, R1-2, R2-5, R4-5)、(A2, B9, R1-3, R2-1, R4-1)、(A2, B9, R1-3, R2-1, R4-2)、(A2, B9, R1-3, R2-1, R4-3)、(A2, B9, R1-3, R2-1, R4-4)、(A2, B9, R1-3, R2-1, R4-5)、(A2, B9, R1-3, R2-2, R4-1)、(A2, B9, R1-3, R2-2, R4-2)、(A2, B9, R1-3, R2-2, R4-3)、(A2, B9, R1-3, R2-2, R4-4)、(A2, B9, R1-3, R2-2, R4-5)、(A2, B9, R1-3, R2-3, R4-1)、(A2, B9, R1-3, R2-3, R4-2)、(A2, B9, R1-3, R2-3, R4-3)、(A2, B9, R1-3, R2-3, R4-4)、(A2, B9, R1-3, R2-3, R4-5)、(A2, B9, R1-3, R2-4, R4-1)、(A2, B9, R1-3, R2-4, R4-2)、(A2, B9, R1-3, R2-4, R4-3)、(A2, B9, R1-3, R2-4, R4-4)、(A2, B9, R1-3, R2-4, R4-5)、(A2, B9, R1-3, R2-5, R4-1)、(A2, B9, R1-3, R2-5, R4-2)、(A2, B9, R1-3, R2-5, R4-3)、(A2, B9, R1-3, R2-5, R4-4)、(A2, B9, R1-3, R2-5, R4-5)、(A2, B10, R1-1, R2-1, R4-1)、(A2, B10, R1-1, R2-1, R4-2)、(A2, B10, R1-1, R2-1, R4-3)、(A2, B10, R1-1, R2-1, R4-4)、(A2, B10, R1-1, R2-1, R4-5)、(A2, B10, R1-1, R2-2, R4-1)、(A2, B10, R1-1, R2-2, R4-2)、(A2, B10, R1-1, R2-2, R4-3)、(A2, B10, R1-1, R2-2, R4-4)、(A2, B10, R1-1, R2-2, R4-5)、(A2, B10, R1-1, R2-3, R4-1)、(A2, B10, R1-1, R2-3, R4-2)、(A2, B10, R1-1, R2-3, R4-3)、(A2, B10, R1-1, R2-3, R4-4)、(A2, B10, R1-1, R2-3, R4-5)、(A2, B10, R1-1, R2-4, R4-1)、(A2, B10, R1-1, R2-4, R4-2)、(A2, B10, R1-1, R2-4, R4-3)、(A2, B10, R1-1, R2-4, R4-4)、(A2, B10, R1-1, R2-4, R4-5)、(A2, B10, R1-1, R2-5, R4-1)、(A2, B10, R1-1, R2-5, R4-2)、(A2, B10, R1-1, R2-5, R4-3)、(A2, B10, R1-1, R2-5, R4-4)、(A2, B10, R1-1, R2-5, R4-5)、(A2, B10, R1-2, R2-1, R4-1)、(A2, B10, R1-2, R2-1, R4-2)、(A2, B10, R1-2, R2-1, R4-3)、(A2, B10, R1-2, R2-1, R4-4)、(A2, B10, R1-2, R2-1, R4-5)、(A2, B10, R1-2, R2-2, R4-1)、(A2, B10, R1-2, R2-2, R4-2)、(A2, B10, R1-2, R2-2, R4-3)、(A2, B10, R
1-2, R2-2, R4-4)、(A2, B10, R1-2, R2-2, R4-5)、(A2, B10, R1-2, R2-3, R4-1)、(A2, B10, R1-2, R2-3, R4-2)、(A2, B10, R1-2, R2-3, R4-3)、(A2, B10, R1-2, R2-3, R4-4)、(A2, B10, R1-2, R2-3, R4-5)、(A2, B10, R1-2, R2-4, R4-1)、(A2, B10, R1-2, R2-4, R4-2)、(A2, B10, R1-2, R2-4, R4-3)、(A2, B10, R1-2, R2-4, R4-4)、(A2, B10, R1-2, R2-4, R4-5)、(A2, B10, R1-2, R2-5, R4-1)、(A2, B10, R1-2, R2-5, R4-2)、(A2, B10, R1-2, R2-5, R4-3)、(A2, B10, R1-2, R2-5, R4-4)、(A2, B10, R1-2, R2-5, R4-5)、(A2, B10, R1-3, R2-1, R4-1)、(A2, B10, R1-3, R2-1, R4-2)、(A2, B10, R1-3, R2-1, R4-3)、(A2, B10, R1-3, R2-1, R4-4)、(A2, B10, R1-3, R2-1, R4-5)、(A2, B10, R1-3, R2-2, R4-1)、(A2, B10, R1-3, R2-2, R4-2)、(A2, B10, R1-3, R2-2, R4-3)、(A2, B10, R1-3, R2-2, R4-4)、(A2, B10, R1-3, R2-2, R4-5)、(A2, B10, R1-3, R2-3, R4-1)、(A2, B10, R1-3, R2-3, R4-2)、(A2, B10, R1-3, R2-3, R4-3)、(A2, B10, R1-3, R2-3, R4-4)、(A2, B10, R1-3, R2-3, R4-5)、(A2, B10, R1-3, R2-4, R4-1)、(A2, B10, R1-3, R2-4, R4-2)、(A2, B10, R1-3, R2-4, R4-3)、(A2, B10, R1-3, R2-4, R4-4)、(A2, B10, R1-3, R2-4, R4-5)、(A2, B10, R1-3, R2-5, R4-1)、(A2, B10, R1-3, R2-5, R4-2)、(A2, B10, R1-3, R2-5, R4-3)、(A2, B10, R1-3, R2-5, R4-4)、(A2, B10, R1-3, R2-5, R4-5)。 Moreover, as this invention compound, following formula (A1)-(A2), (B1)-(B10), (R1-1)-(R1-3), (R2-1)-(R2-5) and ( Compounds having a group to be combined with R4-1) to (R4-5) can also be synthesized.

(A, B, R1, R2, R4) = (A1, B1, R1-1, R2-1, R4-1), (A1, B1, R1-1, R2-1, R4-2), (A1 , B1, R1-1, R2-1, R4-3), (A1, B1, R1-1, R2-1, R4-4), (A1, B1, R1-1, R2-1, R4-5) ), (A1, B1, R1-1, R2-2, R4-1), (A1, B1, R1-1, R2-2, R4-2), (A1, B1, R1-1, R2-2) , R4-3), (A1, B1, R1-1, R2-2, R4-4), (A1, B1, R1-1, R2-2, R4-5), (A1, B1, R1-1) , R2-3, R4-1), (A1, B1, R1-1, R2-3, R4-2), (A1, B1, R1-1, R2-3, R4-3), (A1, B1) , R1-1, R2-3, R4-4), (A1, B1, R1-1, R2-3, R4-5), (A1, B1, R1-1, R2-4, R4-1), (A1, B1, R1-1, R2-4, R4-2), (A1, B1, R1-1, R2-4, R4-3), (A1, B1, R1-1, R2-4, R4 -4), (A1, B1, R1-1, R2-4, R4-5), (A1, B1, R1-1, R2-5, R4-1), (A1, B1, R1-1, R2 -5, R4-2), (A1, B1, R1-1, R2-5, R4-3), (A1, B1, R1-1, R2-5, R4-4), (A1, B1, R1) -1, R2-5, R4-5), (A1, B1, R1-2, R2-1, R4-1), (A1, B1, R1-2, R2-1, R4-2), (A1 , B1, R1-2, R2-1, R4-3), (A1, B1, R1-2, R2-1, R4-4), (A1, B1, R1-2, R2-1, R4-5) ), (A1, B1, R1-2, R2-2, R4-1), (A1, B1, R1-2, R2-2, R4-2), (A1, B1, R1-2, R2-2) , R4-3), (A1, B1, R1-2, R2-2, R4-4), (A1, B1, R1-2, R2-2, R4-5), (A1, B1, R1-2, R2-3, R4-1), (A1, B1, R1-2, R2-3, R4-2), (A1, B1, R1-2, R2-3, R4-3), (A1, B1, R1-2, R2-3, R4-4), (A1, B1, R1-2, R2-3, R4-5), (A1, B1, R1-2, R2-4, R4-1), (A1, B1, R1-2, R2-4, R4-2), ( A1, B1, R1-2, R2-4, R4-3), (A1, B1, R1-2, R2-4, R4-4), (A1, B1, R1-2, R2-4, R4-4) 5), (A1, B1, R1-2, R2-5, R4-1), (A1, B1, R1-2, R2-5, R4-2), (A1, B1, R1-2, R2-) 5, R4-3), (A1, B1, R1-2, R2-5, R4-4), (A1, B1, R1-2, R2-5, R4-5), (A1, B1, R1-) 3, R2-1, R4-1), (A1, B1, R1-3, R2-1, R4-2), (A1, B1, R1-3, R2-1, R4-3), (A1, B1, R1-3, R2-1, R4-4), (A1, B1, R1-3, R2-1, R4-5), (A1, B1, R1-3, R2-2, R4-1) (A1, B1, R1-3, R2-2, R4-2), (A1, B1, R1-3, R2-2, R4-3), (A1, B1, R1-3, R2-2, R2) R4-4), (A1, B1, R1-3, R2-2, R4-5), (A1, B1, R1-3, R2-3, R4-1), (A1, B1, R1-3, R2-3, R4-2), (A1, B1, R1-3, R2-3, R4-3), (A1, B1, R1-3, R2-3, R4-4), (A1, B1, R1-3, R2-3, R4-5), (A1, B1, R1-3, R2-4, R4-1), (A1, B1, R1-3, R2-4, R4-2), ( A1, B1, R1-3, R2-4, R4-3), (A1, B1, R1-3, R2-4, R4-4), (A1, B1, R1-3, R2-4, R4-5), (A1, B1, R1-3, R2-5, R4-1) (A1, B1, R1-3, R2-5, R4-2), (A1, B1, R1-3, R2-5, R4-3), (A1, B1, R1-3, R2-5, R4-4), (A1, B1, R1-3, R2-5, R4-5), (A1, B2, R1-1, R2-1, R4-1), (A1, B2, R1-1, R2-1, R4-2), (A1, B2, R1-1, R2-1, R4-3), (A1, B2, R1-1, R2-1, R4-4), (A1, B2, R1-1, R2-1, R4-5), (A1, B2, R1-1, R2-2, R4-1), (A1, B2, R1-1, R2-2, R4-2), A1, B2, R1-1, R2-2, R4-3), (A1, B2, R1-1, R2-2, R4-4), (A1, B2, R1-1, R2-2, R4-2) 5), (A1, B2, R1-1, R2-3, R4-1), (A1, B2, R1-1, R2-3, R4-2), (A1, B2, R1-1, R2-) 3, R4-3), (A1, B2, R1-1, R2-3, R4-4), (A1, B2, R1-1, R2-3, R4-5), (A1, B2, R1-) 1, R2-4, R4-1), (A1, B2, R1-1, R2-4, R4-2), (A1, B2, R1-1, R2-4, R4-3), (A1, B2) B2, R1-1, R2-4, R4-4), (A1, B2, R1-1, R2-4, R4-5), (A1, B2, R1-1, R2-5, R4-1) (A1, B2, R1-1, R2-5, R4-2), (A1, B2, R1-1, R2-5, R4-3), (A1, B2, R1-1, R2-5, R4-4), (A1, B2, R1-1, R2-5, R4-5), (A1, B2, R1-2, R2-1, R4-1), (A1, B2, R1-2, R2-1, R4-2), (A1, B2, R1-2, R2-1) , R4-3), (A1, B2, R1-2, R2-1, R4-4), (A1, B2, R1-2, R2-1, R4-5), (A1, B2, R1-2) , R2-2, R4-1), (A1, B2, R1-2, R2-2, R4-2), (A1, B2, R1-2, R2-2, R4-3), (A1, B2) , R1-2, R2-2, R4-4), (A1, B2, R1-2, R2-2, R4-5), (A1, B2, R1-2, R2-3, R4-1), (A1, B2, R1-2, R2-3, R4-2), (A1, B2, R1-2, R2-3, R4-3), (A1, B2, R1-2, R2-3, R4 -4), (A1, B2, R1-2, R2-3, R4-5), (A1, B2, R1-2, R2-4, R4-1), (A1, B2, R1-2, R2) -4, R4-2), (A1, B2, R1-2, R2-4, R4-3), (A1, B2, R1-2, R2-4, R4-4), (A1, B2, R1) -2, R2-4, R4-5), (A1, B2, R1-2, R2-5, R4-1), (A1, B2, R1-2, R2-5, R4-2), (A1 , B2, R1-2, R2-5, R4-3), (A1, B2, R1-2, R2-5, R4-4), (A1, B2, R1-2, R2-5, R4-5) ), (A1, B2, R1-3, R2-1, R4-1), (A1, B2, R1-3, R2-1, R4-2), (A1, B2, R1-3, R2-1) , R4-3), (A1, B2, R1-3, R2-1, R4-4), (A1, B2, R1-3, R2-1, R4-5), (A1, B2, R1-3) , R2-2, R4-1), (A1, B2, R1-3, R2-2, R4-2), (A1, B2, R1-3, R2-2, R4-3), (A1, B2) , R1-3, R2-2, R4-4), (A1, B2, R1-3, R2-2, R4-5), (A1, B2, R1-3, R2-3, R4-1), (A1, B2, R1-3, R2-3, R4-2), (A1, B2, R1-3, R2-3, R4-3), (A1, B2, R1-3, R2-3, R4-4), (A1, B2, R1-3, R2-3, R4-5) , (A1, B2, R1-3, R2-4, R4-1), (A1, B2, R1-3, R2-4, R4-2), (A1, B2, R1-3, R2-4, R4-3), (A1, B2, R1-3, R2-4, R4-4), (A1, B2, R1-3, R2-4, R4-5), (A1, B2, R1-3, R2-5, R4-1), (A1, B2, R1-3, R2-5, R4-2), (A1, B2, R1-3, R2-5, R4-3), (A1, B2, R1-3, R2-5, R4-4), (A1, B2, R1-3, R2-5, R4-5), (A1, B3, R1-1, R2-1, R4-1), ( A1, B3, R1-1, R2-1, R4-2), (A1, B3, R1-1, R2-1, R4-3), (A1, B3, R1-1, R2-1, R4-) 4), (A1, B3, R1-1, R2-1, R4-5), (A1, B3, R1-1, R2-2, R4-1), (A1, B3, R1-1, R2- 2, R4-2), (A1, B3, R1-1, R2-2, R4-3), (A1, B3, R1-1, R2-2, R4-4), (A1, B3, R1- 1, R2-2, R4-5), (A1, B3, R1-1, R2-3, R4-1), (A1, B3, R1-1, R2-3, R4-2), (A1, B2) B3, R1-1, R2-3, R4-3), (A1, B3, R1-1, R2-3, R4-4), (A1, B3, R1-1, R2-3, R4-5) , (A1, B3, R1-1, R2-4, R4-1), (A1, B3, R1-1, R2-4, R4-2), (A1, B3, R1-1, R2-4, R4-3), (A1, B3, R1-1, R2-4, R4-4), (A1, B3, R1-1, R2-4, R4-5), (A1, B3, R1-1, R2-5, R4-1), (A1, B3, R1-1, R2- 5, R4-2), (A1, B3, R1-1, R2-5, R4-3), (A1, B3, R1-1, R2-5, R4-4), (A1, B3, R1- 1, R2-5, R4-5), (A1, B3, R1-2, R2-1, R4-1), (A1, B3, R1-2, R2-1, R4-2), (A1, B3, R1-2, R2-1, R4-3), (A1, B3, R1-2, R2-1, R4-4), (A1, B3, R1-2, R2-1, R4-5) (A1, B3, R1-2, R2-2, R4-1), (A1, B3, R1-2, R2-2, R4-2), (A1, B3, R1-2, R2-2, R4-3), (A1, B3, R1-2, R2-2, R4-4), (A1, B3, R1-2, R2-2, R4-5), (A1, B3, R1-2, R2-3, R4-1), (A1, B3, R1-2, R2-3, R4-2), (A1, B3, R1-2, R2-3, R4-3), (A1, B3, R1-2, R2-3, R4-4), (A1, B3, R1-2, R2-3, R4-5), (A1, B3, R1-2, R2-4, R4-1), ( A1, B3, R1-2, R2-4, R4-2), (A1, B3, R1-2, R2-4, R4-3), (A1, B3, R1-2, R2-4, R4) 4), (A1, B3, R1-2, R2-4, R4-5), (A1, B3, R1-2, R2-5, R4-1), (A1, B3, R1-2, R2-) 5, R4-2), (A1, B3, R1-2, R2-5, R4-3), (A1, B3, R1-2, R2-5, R4-4), (A1, B3, R1- 2, R2-5, R4-5), (A1, B3, R1-3, R2-1, R4-1), (A1, B3, R1-3, R2-1, R4-2), (A1, B2) B3, R1-3, R2-1, R4-3), (A1, B3, R1-3, R2-1, R4-4), (A1, B3, R1-3, R2-1, R4-5) , (A1, B3, R1-3, R2-2, R4-1), (A1 , B3, R1-3, R2-2, R4-2), (A1, B3, R1-3, R2-2, R4-3), (A1, B3, R1-3, R2-2, R4-4) ), (A1, B3, R1-3, R2-2, R4-5), (A1, B3, R1-3, R2-3, R4-1), (A1, B3, R1-3, R2-3) , R4-2), (A1, B3, R1-3, R2-3, R4-3), (A1, B3, R1-3, R2-3, R4-4), (A1, B3, R1-3) , R2-3, R4-5), (A1, B3, R1-3, R2-4, R4-1), (A1, B3, R1-3, R2-4, R4-2), (A1, B3) , R1-3, R2-4, R4-3), (A1, B3, R1-3, R2-4, R4-4), (A1, B3, R1-3, R2-4, R4-5), (A1, B3, R1-3, R2-5, R4-1), (A1, B3, R1-3, R2-5, R4-2), (A1, B3, R1-3, R2-5, R4 -3), (A1, B3, R1-3, R2-5, R4-4), (A1, B3, R1-3, R2-5, R4-5), (A1, B4, R1-1, R2) -1, R4-1), (A1, B4, R1-1, R2-1, R4-2), (A1, B4, R1-1, R2-1, R4-3), (A1, B4, R1) -1, R2-1, R4-4), (A1, B4, R1-1, R2-1, R4-5), (A1, B4, R1-1, R2-2, R4-1), (A1 , B4, R1-1, R2-2, R4-2), (A1, B4, R1-1, R2-2, R4-3), (A1, B4, R1-1, R2-2, R4-4) ), (A1, B4, R1-1, R2-2, R4-5), (A1, B4, R1-1, R2-3, R4-1), (A1, B4, R1-1, R2-3) , R4-2), (A1, B4, R1-1, R2-3, R4-3), (A1, B4, R1-1, R2-3, R4-4), (A1, B4, R1-1) , R2-3, R4-5), (A1, B4, R1-1, R2 -4, R4-1), (A1, B4, R1-1, R2-4, R4-2), (A1, B4, R1-1, R2-4, R4-3), (A1, B4, R1) -1, R2-4, R4-4), (A1, B4, R1-1, R2-4, R4-5), (A1, B4, R1-1, R2-5, R4-1), (A1 , B4, R1-1, R2-5, R4-2), (A1, B4, R1-1, R2-5, R4-3), (A1, B4, R1-1, R2-5, R4-4) ), (A1, B4, R1-1, R2-5, R4-5), (A1, B4, R1-2, R2-1, R4-1), (A1, B4, R1-2, R2-1) , R4-2), (A1, B4, R1-2, R2-1, R4-3), (A1, B4, R1-2, R2-1, R4-4), (A1, B4, R1-2) , R2-1, R4-5), (A1, B4, R1-2, R2-2, R4-1), (A1, B4, R1-2, R2-2, R4-2), (A1, B4) , R1-2, R2-2, R4-3), (A1, B4, R1-2, R2-2, R4-4), (A1, B4, R1-2, R2-2, R4-5), (A1, B4, R1-2, R2-3, R4-1), (A1, B4, R1-2, R2-3, R4-2), (A1, B4, R1-2, R2-3, R4) -3), (A1, B4, R1-2, R2-3, R4-4), (A1, B4, R1-2, R2-3, R4-5), (A1, B4, R1-2, R2) -4, R4-1), (A1, B4, R1-2, R2-4, R4-2), (A1, B4, R1-2, R2-4, R4-3), (A1, B4, R1) -2, R2-4, R4-4), (A1, B4, R1-2, R2-4, R4-5), (A1, B4, R1-2, R2-5, R4-1), (A1 , B4, R1-2, R2-5, R4-2), (A1, B4, R1-2, R2-5, R4-3), (A1, B4, R1-2, R2-5, R4-4) ), (A1, B4, R1-2, R2-5, R4-5), (A 1, B4, R1-3, R2-1, R4-1), (A1, B4, R1-3, R2-1, R4-2), (A1, B4, R1-3, R2-1, R4-) 3), (A1, B4, R1-3, R2-1, R4-4), (A1, B4, R1-3, R2-1, R4-5), (A1, B4, R1-3, R2-) 2, R4-1), (A1, B4, R1-3, R2-2, R4-2), (A1, B4, R1-3, R2-2, R4-3), (A1, B4, R1-) 3, R2-2, R4-4), (A1, B4, R1-3, R2-2, R4-5), (A1, B4, R1-3, R2-3, R4-1), (A1, B4) B4, R1-3, R2-3, R4-2), (A1, B4, R1-3, R2-3, R4-3), (A1, B4, R1-3, R2-3, R4-4) , (A1, B4, R1-3, R2-3, R4-5), (A1, B4, R1-3, R2-4, R4-1), (A1, B4, R1-3, R2-4, R4-2), (A1, B4, R1-3, R2-4, R4-3), (A1, B4, R1-3, R2-4, R4-4), (A1, B4, R1-3, R2-4, R4-5), (A1, B4, R1-3, R2-5, R4-1), (A1, B4, R1-3, R2-5, R4-2), (A1, B4, S4) R1-3, R2-5, R4-3), (A1, B4, R1-3, R2-5, R4-4), (A1, B4, R1-3, R2-5, R4-5), ( A1, B5, R1-1, R2-1, R4-1), (A1, B5, R1-1, R2-1, R4-2), (A1, B5, R1-1, R2-1, R4-) 3), (A1, B5, R1-1, R2-1, R4-4), (A1, B5, R1-1, R2-1, R4-5), (A1, B5, R1-1, R2-) 2, R4-1), (A1, B5, R1-1, R2-2, R4-2), (A1, B5, R1-1, R2-2, R4-3), (A1, B5, R1-) 1, R2-2, R4-4), (A1, B5, R1-1, R 2-2, R4-5), (A1, B5, R1-1, R2-3, R4-1), (A1, B5, R1-1, R2-3, R4-2), (A1, B5, R1-1, R2-3, R4-3), (A1, B5, R1-1, R2-3, R4-4), (A1, B5, R1-1, R2-3, R4-5), A1, B5, R1-1, R2-4, R4-1), (A1, B5, R1-1, R2-4, R4-2), (A1, B5, R1-1, R2-4, R4-) 3), (A1, B5, R1-1, R2-4, R4-4), (A1, B5, R1-1, R2-4, R4-5), (A1, B5, R1-1, R2-) 5, R4-1), (A1, B5, R1-1, R2-5, R4-2), (A1, B5, R1-1, R2-5, R4-3), (A1, B5, R1-) 1, R2-5, R4-4), (A1, B5, R1-1, R2-5, R4-5), (A1, B5, R1-2, R2-1, R4-1), (A1, B5, R1-2, R2-1, R4-2), (A1, B5, R1-2, R2-1, R4-3), (A1, B5, R1-2, R2-1, R4-4) , (A1, B5, R1-2, R2-1, R4-5), (A1, B5, R1-2, R2-2, R4-1), (A1, B5, R1-2, R2-2, R4-2), (A1, B5, R1-2, R2-2, R4-3), (A1, B5, R1-2, R2-2, R4-4), (A1, B5, R1-2, R2-2, R4-5), (A1, B5, R1-2, R2-3, R4-1), (A1, B5, R1-2, R2-3, R4-2), (A1, B5, R1-2, R2-3, R4-3), (A1, B5, R1-2, R2-3, R4-4), (A1, B5, R1-2, R2-3, R4-5), ( A1, B5, R1-2, R2-4, R4-1), (A1, B5, R1-2, R2-4, R4-2), (A1, B5, R1-2, R2-4, R4-4) 3), (A1, B5, R1-2, R2-4, R4-4), ( A1, B5, R1-2, R2-4, R4-5), (A1, B5, R1-2, R2-5, R4-1), (A1, B5, R1-2, R2-5, R4-4) 2), (A1, B5, R1-2, R2-5, R4-3), (A1, B5, R1-2, R2-5, R4-4), (A1, B5, R1-2, R2-) 5, R4-5), (A1, B5, R1-3, R2-1, R4-1), (A1, B5, R1-3, R2-1, R4-2), (A1, B5, R1-) 3, R2-1, R4-3), (A1, B5, R1-3, R2-1, R4-4), (A1, B5, R1-3, R2-1, R4-5), (A1, B3) B5, R1-3, R2-2, R4-1), (A1, B5, R1-3, R2-2, R4-2), (A1, B5, R1-3, R2-2, R4-3) (A1, B5, R1-3, R2-2, R4-4), (A1, B5, R1-3, R2-2, R4-5), (A1, B5, R1-3, R2-3, R4-1), (A1, B5, R1-3, R2-3, R4-2), (A1, B5, R1-3, R2-3, R4-3), (A1, B5, R1-3, R2-3, R4-4), (A1, B5, R1-3, R2-3, R4-5),
(A1, B5, R1-3, R2-4, R4-1), (A1, B5, R1-3, R2-4, R4-2), (A1, B5, R1-3, R2-4, R4 -3), (A1, B5, R1-3, R2-4, R4-4), (A1, B5, R1-3, R2-4, R4-5), (A1, B5, R1-3, R2) -5, R4-1), (A1, B5, R1-3, R2-5, R4-2), (A1, B5, R1-3, R2-5, R4-3), (A1, B5, R1) -3, R2-5, R4-4), (A1, B5, R1-3, R2-5, R4-5), (A1, B6, R1-1, R2-1, R4-1), (A1 , B6, R1-1, R2-1, R4-2), (A1, B6, R1-1, R2-1, R4-3), (A1, B6, R1-1, R2-1, R4-4) ), (A1, B6, R1-1, R2-1, R4-5), (A1, B6, R1-1, R2-2, R4-1), (A1, B6, R1-1, R2-2) , R4-2), (A1, B6, R1-1, R2-2, R4-3), (A1, B6, R1-1, R2-2, R4-4), (A1, B6, R1-1) , R2-2, R4-5), (A1, B6, R1-1, R2-3, R4-1), (A1, B6, R1-1, R2-3, R4-2), (A1, B6) , R1-1, R2-3, R4-3), (A1, B6, R1-1, R2-3, R4-4), (A1, B6, R1-1, R2-3, R4-5), (A1, B6, R1-1, R2-4, R4-1), (A1, B6, R1-1, R2-4, R4-2), (A1, B6, R1-1, R2-4, R4 -3), (A1, B6, R1-1, R2-4, R4-4), (A1, B6, R1-1, R2-4, R4-5), (A1, B6, R1-1, R2) -5, R4-1), (A1, B6, R1-1, R2-5, R4-2), (A1, B6, R1-1, R2-5, R4-3), (A1, B6, R1) -1, R2-5, R4-4), (A1, B6, R1-1, R2-5, R4-5), (A1, B6, R1-2, R2-1, R4-1), (A1, B6, R1-2, R2-1, R4-2), (A1, B6, R1-2, R2-1, R4-3), (A1, B6, R1-2, R2-1, R4-4), (A1, B6, R1-2, R2-1, R4-5), ( A1, B6, R1-2, R2-2, R4-1), (A1, B6, R1-2, R2-2, R4-2), (A1, B6, R1-2, R2-2, R4-2, R4) 3), (A1, B6, R1-2, R2-2, R4-4), (A1, B6, R1-2, R2-2, R4-5), (A1, B6, R1-2, R2-) 3, R4-1), (A1, B6, R1-2, R2-3, R4-2), (A1, B6, R1-2, R2-3, R4-3), (A1, B6, R1-) 2, R2-3, R4-4), (A1, B6, R1-2, R2-3, R4-5), (A1, B6, R1-2, R2-4, R4-1), (A1, B2) B6, R1-2, R2-4, R4-2), (A1, B6, R1-2, R2-4, R4-3), (A1, B6, R1-2, R2-4, R4-4) (A1, B6, R1-2, R2-4, R4-5), (A1, B6, R1-2, R2-5, R4-1), (A1, B6, R1-2, R2-5, R4-2), (A1, B6, R1-2, R2-5, R4-3), (A1, B6, R1-2, R2-5, R4-4), (A1, B6, R1-2, R2-5, R4-5), (A1, B6, R1-3, R2-1, R4-1), (A1, B6, R1-3, R2-1, R4-2), (A1, B6, R1-3, R2-1, R4-3), (A1, B6, R1-3, R2-1, R4-4), (A1, B6, R1-3, R2-1, R4-5), ( A1, B6, R1-3, R2-2, R4-1), (A1, B6, R1-3, R2-2, R4-2), (A1, B6, R1-3, R2-2, R4-2) 3), (A1, B6, R1-3, R2-2, R4-4) (A1, B6, R1-3, R2-2, R4-5), (A1, B6, R1-3, R2-3, R4-1), (A1, B6, R1-3, R2-3, R4 -2), (A1, B6, R1-3, R2-3, R4-3), (A1, B6, R1-3, R2-3, R4-4), (A1, B6, R1-3, R2) -3, R4-5), (A1, B6, R1-3, R2-4, R4-1), (A1, B6, R1-3, R2-4, R4-2), (A1, B6, R1) -3, R2-4, R4-3), (A1, B6, R1-3, R2-4, R4-4), (A1, B6, R1-3, R2-4, R4-5), (A1 , B6, R1-3, R2-5, R4-1), (A1, B6, R1-3, R2-5, R4-2), (A1, B6, R1-3, R2-5, R4-3) ), (A1, B6, R1-3, R2-5, R4-4), (A1, B6, R1-3, R2-5, R4-5), (A1, B7, R1-1, R2-1) , R4-1), (A1, B7, R1-1, R2-1, R4-2), (A1, B7, R1-1, R2-1, R4-3), (A1, B7, R1-1) , R2-1, R4-4), (A1, B7, R1-1, R2-1, R4-5), (A1, B7, R1-1, R2-2, R4-1), (A1, B7) , R1-1, R2-2, R4-2), (A1, B7, R1-1, R2-2, R4-3), (A1, B7, R1-1, R2-2, R4-4), (A1, B7, R1-1, R2-2, R4-5), (A1, B7, R1-1, R2-3, R4-1), (A1, B7, R1-1, R2-3, R4 -2), (A1, B7, R1-1, R2-3, R4-3), (A1, B7, R1-1, R2-3, R4-4), (A1, B7, R1-1, R2 -3, R4-5), (A1, B7, R1-1, R2-4, R4-1), (A1, B7, R1-1, R2-4, R4-2), (A1, B7, R1) -1, R2-4, R4-3), (A1, B7, R1-1) , R2-4, R4-4), (A1, B7, R1-1, R2-4, R4-5), (A1, B7, R1-1, R2-5, R4-1), (A1, B7) , R1-1, R2-5, R4-2), (A1, B7, R1-1, R2-5, R4-3), (A1, B7, R1-1, R2-5, R4-4), (A1, B7, R1-1, R2-5, R4-5), (A1, B7, R1-2, R2-1, R4-1), (A1, B7, R1-2, R2-1, R4 -2), (A1, B7, R1-2, R2-1, R4-3), (A1, B7, R1-2, R2-1, R4-4), (A1, B7, R1-2, R2) -1, R4-5), (A1, B7, R1-2, R2-2, R4-1), (A1, B7, R1-2, R2-2, R4-2), (A1, B7, R1) -2, R2-2, R4-3), (A1, B7, R1-2, R2-2, R4-4), (A1, B7, R1-2, R2-2, R4-5), (A1 , B7, R1-2, R2-3, R4-1), (A1, B7, R1-2, R2-3, R4-2), (A1, B7, R1-2, R2-3, R4-3) ), (A1, B7, R1-2, R2-3, R4-4), (A1, B7, R1-2, R2-3, R4-5), (A1, B7, R1-2, R2-4) , R4-1), (A1, B7, R1-2, R2-4, R4-2), (A1, B7, R1-2, R2-4, R4-3), (A1, B7, R1-2) , R2-4, R4-4), (A1, B7, R1-2, R2-4, R4-5), (A1, B7, R1-2, R2-5, R4-1), (A1, B7) , R1-2, R2-5, R4-2), (A1, B7, R1-2, R2-5, R4-3), (A1, B7, R1-2, R2-5, R4-4), (A1, B7, R1-2, R2-5, R4-5), (A1, B7, R1-3, R2-1, R4-1), (A1, B7, R1-3, R2-1, R4 -2), (A1, B7, R1-3, R2-1, R4-3) (A1, B7, R1-3, R2-1, R4-4), (A1, B7, R1-3, R2-1, R4-5), (A1, B7, R1-3, R2-2, R4 -1), (A1, B7, R1-3, R2-2, R4-2), (A1, B7, R1-3, R2-2, R4-3), (A1, B7, R1-3, R2) -2, R4-4), (A1, B7, R1-3, R2-2, R4-5), (A1, B7, R1-3, R2-3, R4-1), (A1, B7, R1) -3, R2-3, R4-2), (A1, B7, R1-3, R2-3, R4-3), (A1, B7, R1-3, R2-3, R4-4), (A1 , B7, R1-3, R2-3, R4-5), (A1, B7, R1-3, R2-4, R4-1), (A1, B7, R1-3, R2-4, R4-2) ), (A1, B7, R1-3, R2-4, R4-3), (A1, B7, R1-3, R2-4, R4-4), (A1, B7, R1-3, R2-4) , R4-5), (A1, B7, R1-3, R2-5, R4-1), (A1, B7, R1-3, R2-5, R4-2), (A1, B7, R1-3) , R2-5, R4-3), (A1, B7, R1-3, R2-5, R4-4), (A1, B7, R1-3, R2-5, R4-5), (A1, B8) , R1-1, R2-1, R4-1), (A1, B8, R1-1, R2-1, R4-2), (A1, B8, R1-1, R2-1, R4-3), (A1, B8, R1-1, R2-1, R4-4), (A1, B8, R1-1, R2-1, R4-5), (A1, B8, R1-1, R2-2, R4 -1), (A1, B8, R1-1, R2-2, R4-2), (A1, B8, R1-1, R2-2, R4-3), (A1, B8, R1-1, R2 -2, R4-4), (A1, B8, R1-1, R2-2, R4-5), (A1, B8, R1-1, R2-3, R4-1), (A1, B8, R1) -1, R2-3, R4-2), (A1, B8, R1-) 1, R2-3, R4-3), (A1, B8, R1-1, R2-3, R4-4), (A1, B8, R1-1, R2-3, R4-5), (A1, B1) B8, R1-1, R2-4, R4-1), (A1, B8, R1-1, R2-4, R4-2), (A1, B8, R1-1, R2-4, R4-3) (A1, B8, R1-1, R2-4, R4-4), (A1, B8, R1-1, R2-4, R4-5), (A1, B8, R1-1, R2-5, R4-1), (A1, B8, R1-1, R2-5, R4-2), (A1, B8, R1-1, R2-5, R4-3), (A1, B8, R1-1, R2-5, R4-4), (A1, B8, R1-1, R2-5, R4-5), (A1, B8, R1-2, R2-1, R4-1), (A1, B8, R1-2, R2-1, R4-2), (A1, B8, R1-2, R2-1, R4-3), (A1, B8, R1-2, R2-1, R4-4), ( A1, B8, R1-2, R2-1, R4-5), (A1, B8, R1-2, R2-2, R4-1), (A1, B8, R1-2, R2-2, R4-2) 2), (A1, B8, R1-2, R2-2, R4-3), (A1, B8, R1-2, R2-2, R4-4), (A1, B8, R1-2, R2-) 2, R4-5), (A1, B8, R1-2, R2-3, R4-1), (A1, B8, R1-2, R2-3, R4-2), (A1, B8, R1-) 2, R2-3, R4-3), (A1, B8, R1-2, R2-3, R4-4), (A1, B8, R1-2, R2-3, R4-5), (A1, B2) B8, R1-2, R2-4, R4-1), (A1, B8, R1-2, R2-4, R4-2), (A1, B8, R1-2, R2-4, R4-3) , (A1, B8, R1-2, R2-4, R4-4), (A1, B8, R1-2, R2-4, R4-5), (A1, B8, R1-2, R2-5, R4-1), (A1, B8, R1-2, R2-5, R4-2) (A1, B8, R1-2, R2-5, R4-3), (A1, B8, R1-2, R2-5, R4-4), (A1, B8, R1-2, R2-5, R4-5), (A1, B8, R1-3, R2-1, R4-1), (A1, B8, R1-3, R2-1, R4-2), (A1, B8, R1-3, R2-1, R4-3), (A1, B8, R1-3, R2-1, R4-4), (A1, B8, R1-3, R2-1, R4-5), (A1, B8, R1-3, R2-2, R4-1), (A1, B8, R1-3, R2-2, R4-2), (A1, B8, R1-3, R2-2, R4-3), ( A1, B8, R1-3, R2-2, R4-4), (A1, B8, R1-3, R2-2, R4-5), (A1, B8, R1-3, R2-3, R4) 1), (A1, B8, R1-3, R2-3, R4-2), (A1, B8, R1-3, R2-3, R4-3), (A1, B8, R1-3, R2-) 3, R4-4), (A1, B8, R1-3, R2-3, R4-5), (A1, B8, R1-3, R2-4, R4-1), (A1, B8, R1-) 3, R2-4, R4-2), (A1, B8, R1-3, R2-4, R4-3), (A1, B8, R1-3, R2-4, R4-4), (A1, B3) B8, R1-3, R2-4, R4-5), (A1, B8, R1-3, R2-5, R4-1), (A1, B8, R1-3, R2-5, R4-2) (A1, B8, R1-3, R2-5, R4-3), (A1, B8, R1-3, R2-5, R4-4), (A1, B8, R1-3, R2-5, R4-5), (A1, B9, R1-1, R2-1, R4-1), (A1, B9, R1-1, R2-1, R4-2), (A1, B9, R1-1, R2-1, R4-3), (A1, B9, R1-1, R2-1, R4-4), (A1, B9, R1-1, R2-1, R4-5), (A1, B9, R1-1, R2-2, R4-1), (A1, B9, R1 -1, R2-2, R4-2), (A1, B9, R1-1, R2-2, R4-3), (A1, B9, R1-1, R2-2, R4-4), (A1 , B9, R1-1, R2-2, R4-5), (A1, B9, R1-1, R2-3, R4-1), (A1, B9, R1-1, R2-3, R4-2) ), (A1, B9, R1-1, R2-3, R4-3), (A1, B9, R1-1, R2-3, R4-4), (A1, B9, R1-1, R2-3) , R4-5), (A1, B9, R1-1, R2-4, R4-1), (A1, B9, R1-1, R2-4, R4-2), (A1, B9, R1-1) , R2-4, R4-3), (A1, B9, R1-1, R2-4, R4-4), (A1, B9, R1-1, R2-4, R4-5), (A1, B9) , R1-1, R2-5, R4-1), (A1, B9, R1-1, R2-5, R4-2), (A1, B9, R1-1, R2-5, R4-3), (A1, B9, R1-1, R2-5, R4-4), (A1, B9, R1-1, R2-5, R4-5), (A1, B9, R1-2, R2-1, R4 -1), (A1, B9, R1-2, R2-1, R4-2), (A1, B9, R1-2, R2-1, R4-3), (A1, B9, R1-2, R2) -1, R4-4), (A1, B9, R1-2, R2-1, R4-5), (A1, B9, R1-2, R2-2, R4-1), (A1, B9, R1) -2, R2-2, R4-2), (A1, B9, R1-2, R2-2, R4-3), (A1, B9, R1-2, R2-2, R4-4), (A1 , B9, R1-2, R2-2, R4-5), (A1, B9, R1-2, R2-3, R4-1), (A1, B9, R1-2, R2-3, R4-2) ), (A1, B9, R1-2, R2-3, R4-3), (A1, B9, R1-2, R2-3, R4-4), (A1, B9, R1-2, R2-3) , R4-5), (A1, B9, R1-2, R2-4, R4-1) ), (A1, B9, R1-2, R2-4, R4-2), (A1, B9, R1-2, R2-4, R4-3), (A1, B9, R1-2, R2-4) , R4-4), (A1, B9, R1-2, R2-4, R4-5), (A1, B9, R1-2, R2-5, R4-1), (A1, B9, R1-2) , R2-5, R4-2), (A1, B9, R1-2, R2-5, R4-3), (A1, B9, R1-2, R2-5, R4-4), (A1, B9) , R1-2, R2-5, R4-5), (A1, B9, R1-3, R2-1, R4-1), (A1, B9, R1-3, R2-1, R4-2), (A1, B9, R1-3, R2-1, R4-3), (A1, B9, R1-3, R2-1, R4-4), (A1, B9, R1-3, R2-1, R4 -5), (A1, B9, R1-3, R2-2, R4-1), (A1, B9, R1-3, R2-2, R4-2), (A1, B9, R1-3, R2) -2, R4-3), (A1, B9, R1-3, R2-2, R4-4), (A1, B9, R1-3, R2-2, R4-5), (A1, B9, R1) -3, R2-3, R4-1), (A1, B9, R1-3, R2-3, R4-2), (A1, B9, R1-3, R2-3, R4-3), (A1 , B9, R1-3, R2-3, R4-4), (A1, B9, R1-3, R2-3, R4-5), (A1, B9, R1-3, R2-4, R4-1) ), (A1, B9, R1-3, R2-4, R4-2), (A1, B9, R1-3, R2-4, R4-3), (A1, B9, R1-3, R2-4) , R4-4), (A1, B9, R1-3, R2-4, R4-5), (A1, B9, R1-3, R2-5, R4-1), (A1, B9, R1-3) , R2-5, R4-2), (A1, B9, R1-3, R2-5, R4-3), (A1, B9, R1-3, R2-5, R4-4), (A1, B9) , R1-3, R2-5, R4-5), (A1, B10, R1-1, R2-1, R4-1), (A1, B10, R1-1, R2-1, R4-2), (A1, B10, R1-1, R2-1, R4-3), ( A1, B10, R1-1, R2-1, R4-4), (A1, B10, R1-1, R2-1, R4-5), (A1, B10, R1-1, R2-2, R4-4) 1), (A1, B10, R1-1, R2-2, R4-2), (A1, B10, R1-1, R2-2, R4-3), (A1, B10, R1-1, R2-) 2, R4-4), (A1, B10, R1-1, R2-2, R4-5), (A1, B10, R1-1, R2-3, R4-1), (A1, B10, R1-) 1, R2-3, R4-2), (A1, B10, R1-1, R2-3, R4-3), (A1, B10, R1-1, R2-3, R4-4), (A1, B1 B10, R1-1, R2-3, R4-5), (A1, B10, R1-1, R2-4, R4-1), (A1, B10, R1-1, R2-4, R4-2) (A1, B10, R1-1, R2-4, R4-3), (A1, B10, R1-1, R2-4, R4-4), (A1, B10, R1-1, R2-4, R4-5), (A1, B10, R1-1, R2-5, R4-1), (A1, B10, R1-1, R2-5, R4-2), (A1, B10, R1-1, R2-5, R4-3), (A1, B10, R1-1, R2-5, R4-4), (A1, B10, R1-1, R2-5, R4-5), (A1, B10, R1-2, R2-1, R4-1), (A1, B10, R1-2, R2-1, R4-2), (A1, B10, R1-2, R2-1, R4-3), ( A1, B10, R1-2, R2-1, R4-4), (A1, B10, R1-2, R2-1, R4-5), (A1, B10, R1-2, R2-2, R4-2) 1), (A1, B10, R1-2, R2-2, R4-2), (A1, B10, R1-2, R2-2, R4-3), (A1, B10, R1-2, R2-) 2 , R4-4), (A1, B10, R1-2, R2-2, R4-5), (A1, B10, R1-2, R2-3, R4-1), (A1, B10, R1-2) , R2-3, R4-2), (A1, B10, R1-2, R2-3, R4-3), (A1, B10, R1-2, R2-3, R4-4), (A1, B10) , R1-2, R2-3, R4-5), (A1, B10, R1-2, R2-4, R4-1), (A1, B10, R1-2, R2-4, R4-2), (A1, B10, R1-2, R2-4, R4-3), (A1, B10, R1-2, R2-4, R4-4), (A1, B10, R1-2, R2-4, R4 -5), (A1, B10, R1-2, R2-5, R4-1), (A1, B10, R1-2, R2-5, R4-2), (A1, B10, R1-2, R2) -5, R4-3), (A1, B10, R1-2, R2-5, R4-4), (A1, B10, R1-2, R2-5, R4-5), (A1, B10, R1) -3, R2-1, R4-1), (A1, B10, R1-3, R2-1, R4-2), (A1, B10, R1-3, R2-1, R4-3), (A1 , B10, R1-3, R2-1, R4
-4), (A1, B10, R1-3, R2-1, R4-5), (A1, B10, R1-3, R2-2, R4-1), (A1, B10, R1-3, R2) -2, R4-2), (A1, B10, R1-3, R2-2, R4-3), (A1, B10, R1-3, R2-2, R4-4), (A1, B10, R1) -3, R2-2, R4-5), (A1, B10, R1-3, R2-3, R4-1), (A1, B10, R1-3, R2-3, R4-2), (A1 , B10, R1-3, R2-3, R4-3), (A1, B10, R1-3, R2-3, R4-4), (A1, B10, R1-3, R2-3, R4-5) ), (A1, B10, R1-3, R2-4, R4-1), (A1, B10, R1-3, R2-4, R4-2), (A1, B10, R1-3, R2-4) , R4-3), (A1, B10, R1-3, R2-4, R4-4), (A1, B10, R1-3, R2-4, R4-5), (A1, B10, R1-3) , R2-5, R4-1), (A1, B10, R1-3, R2-5, R4-2), (A1, B10, R1-3, R2-5, R4-3), (A1, B10) , R1-3, R2-5, R4-4), (A1, B10, R1-3, R2-5, R4-5), (A2, B1, R1-1, R2-1, R4-1), (A2, B1, R1-1, R2-1, R4-2), (A2, B1, R1-1, R2-1, R4-3), (A2, B1, R1-1, R2-1, R4 -4), (A2, B1, R1-1, R2-1, R4-5), (A2, B1, R1-1, R2-2, R4-1), (A2, B1, R1-1, R2 -2, R4-2), (A2, B1, R1-1, R2-2, R4-3), (A2, B1, R1-1, R2-2, R4-4), (A2, B1, R1) -1, R2-2, R4-5), (A2, B1, R1-1, R2-3, R4-1), (A2, B1, R1-1, R2-3, R4-2), (A2 , B1, R1-1, R 2-3, R4-3), (A2, B1, R1-1, R2-3, R4-4), (A2, B1, R1-1, R2-3, R4-5), (A2, B1, B2) R1-1, R2-4, R4-1), (A2, B1, R1-1, R2-4, R4-2), (A2, B1, R1-1, R2-4, R4-3), A2, B1, R1-1, R2-4, R4-4), (A2, B1, R1-1, R2-4, R4-5), (A2, B1, R1-1, R2-5, R4-4) 1), (A2, B1, R1-1, R2-5, R4-2), (A2, B1, R1-1, R2-5, R4-3), (A2, B1, R1-1, R2-) 5, R4-4), (A2, B1, R1-1, R2-5, R4-5), (A2, B1, R1-2, R2-1, R4-1), (A2, B1, R1-) 2, R2-1, R4-2), (A2, B1, R1-2, R2-1, R4-3), (A2, B1, R1-2, R2-1, R4-4), (A2, B2 B1, R1-2, R2-1, R4-5), (A2, B1, R1-2, R2-2, R4-1), (A2, B1, R1-2, R2-2, R4-2) (A2, B1, R1-2, R2-2, R4-3), (A2, B1, R1-2, R2-2, R4-4), (A2, B1, R1-2, R2-2, R4-5), (A2, B1, R1-2, R2-3, R4-1), (A2, B1, R1-2, R2-3, R4-2), (A2, B1, R1-2, R2-3, R4-3), (A2, B1, R1-2, R2-3, R4-4), (A2, B1, R1-2, R2-3, R4-5), (A2, B1, B2) R1-2, R2-4, R4-1), (A2, B1, R1-2, R2-4, R4-2), (A2, B1, R1-2, R2-4, R4-3), ( A2, B1, R1-2, R2-4, R4-4), (A2, B1, R1-2, R2-4, R4-5), (A2, B1, R1-2, R2-5, R4-4) 1), (A2, B1, R1-2, R2-5, R4-2), (A A2, B1, R1-2, R2-5, R4-3), (A2, B1, R1-2, R2-5, R4-4), (A2, B1, R1-2, R2-5, R4-4) 5), (A2, B1, R1-3, R2-1, R4-1), (A2, B1, R1-3, R2-1, R4-2), (A2, B1, R1-3, R2- 1, R4-3), (A2, B1, R1-3, R2-1, R4-4), (A2, B1, R1-3, R2-1, R4-5), (A2, B1, R1-) 3, R2-2, R4-1), (A2, B1, R1-3, R2-2, R4-2), (A2, B1, R1-3, R2-2, R4-3), (A2, B2) B1, R1-3, R2-2, R4-4), (A2, B1, R1-3, R2-2, R4-5), (A2, B1, R1-3, R2-3, R4-1) , (A2, B1, R1-3, R2-3, R4-2), (A2, B1, R1-3, R2-3, R4-3), (A2, B1, R1-3, R2-3, R4-4), (A2, B1, R1-3, R2-3, R4-5), (A2, B1, R1-3, R2-4, R4-1), (A2, B1, R1-3, R2-4, R4-2), (A2, B1, R1-3, R2-4, R4-3), (A2, B1, R1-3, R2-4, R4-4), (A2, B1, B2) R1-3, R2-4, R4-5), (A2, B1, R1-3, R2-5, R4-1), (A2, B1, R1-3, R2-5, R4-2), ( A2, B1, R1-3, R2-5, R4-3), (A2, B1, R1-3, R2-5, R4-4), (A2, B1, R1-3, R2-5, R4-4) 5), (A2, B2, R1-1, R2-1, R4-1), (A2, B2, R1-1, R2-1, R4-2), (A2, B2, R1-1, R2- 1, R4-3), (A2, B2, R1-1, R2-1, R4-4), (A2, B2, R1-1, R2-1, R4-5), (A2, B2, R1- 1, R2-2, R4-1), (A2, B2, R1-1, R2-2, R4-2), (A2, B2, R1-1, R2-2, R4-3), (A2, B2, R1-1, R2-2, R4-4), (A2, B2, R1-1, R2-2, R4-5), (A2, B2, R1-1, R2-3, R4-1), (A2, B2, R1-1, R2-3, R4-2), A2, B2, R1-1, R2-3, R4-3), (A2, B2, R1-1, R2-3, R4-4), (A2, B2, R1-1, R2-3, R4-) 5), (A2, B2, R1-1, R2-4, R4-1), (A2, B2, R1-1, R2-4, R4-2), (A2, B2, R1-1, R2-) 4, R4-3), (A2, B2, R1-1, R2-4, R4-4), (A2, B2, R1-1, R2-4, R4-5), (A2, B2, R1- 1, R2-5, R4-1), (A2, B2, R1-1, R2-5, R4-2), (A2, B2, R1-1, R2-5, R4-3), (A2, B2, R1-1, R2-5, R4-4), (A2, B2, R1-1, R2-5, R4-5), (A2, B2, R1-2, R2-1, R4-1) , (A2, B2, R1-2, R2-1, R4-2), (A2, B2, R1-2, R2-1, R4-3), (A2, B2, R1-2, R2-1, R4-4), (A2, B2, R1-2, R2-1, R4-5), (A2, B2, R1-2, R2-2, R4-1), (A2, B2, R1-2, R2-2, R4-2), (A2, B2, R1-2, R2-2, R4-3), (A2, B2, R1-2, R2-2, R4-4), (A2, B2, R1-2, R2-2, R4-5), (A2, B2, R1-2, R2-3, R4-1), (A2, B2, R1-2, R2-3, R4-2), ( A2, B2, R1-2, R2-3, R4-3), (A2, B2, R1-2, R2-3, R4-4), (A2, B2, R1-2, R2-3, R4-4) 5), (A2, B2, R1-2, R2-4, R4-1), (A2, B2, R1-2, R2-4, R4-2), (A2, B2, R1-2, R2-4, R4-3), (A2, B2, R1-2, R2-4, R4 -4), (A2, B2, R1-2, R2-4, R4-5), (A2, B2, R1-2, R2-5, R4-1), (A2, B2, R1-2, R2 -5, R4-2), (A2, B2, R1-2, R2-5, R4-3), (A2, B2, R1-2, R2-5, R4-4), (A2, B2, R1) -2, R2-5, R4-5), (A2, B2, R1-3, R2-1, R4-1), (A2, B2, R1-3, R2-1, R4-2), (A2 , B2, R1-3, R2-1, R4-3), (A2, B2, R1-3, R2-1, R4-4), (A2, B2, R1-3, R2-1, R4-5) ), (A2, B2, R1-3, R2-2, R4-1), (A2, B2, R1-3, R2-2, R4-2), (A2, B2, R1-3, R2-2) , R4-3), (A2, B2, R1-3, R2-2, R4-4), (A2, B2, R1-3, R2-2, R4-5), (A2, B2, R1-3) , R2-3, R4-1), (A2, B2, R1-3, R2-3, R4-2), (A2, B2, R1-3, R2-3, R4-3), (A2, B2) , R1-3, R2-3, R4-4), (A2, B2, R1-3, R2-3, R4-5), (A2, B2, R1-3, R2-4, R4-1), (A2, B2, R1-3, R2-4, R4-2), (A2, B2, R1-3, R2-4, R4-3), (A2, B2, R1-3, R2-4, R4 -4), (A2, B2, R1-3, R2-4, R4-5), (A2, B2, R1-3, R2-5, R4-1), (A2, B2, R1-3, R2 -5, R4-2), (A2, B2, R1-3, R2-5, R4-3), (A2, B2, R1-3, R2-5, R4-4), (A2, B2, R1) -3, R2-5, R4-5), (A2, B3, R1-1, R2-1, R4-1), (A2, B3, R1-1, R2-1, R4-2), (A2, B3, R1-1, R2-1, R4-3), (A2, B3, R1-1, R2-1, R4-4), (A2, B3, R1-1, R2-1, R4-5), (A2, B3, R1-1, R2-2, R4-1), A2, B3, R1-1, R2-2, R4-2), (A2, B3, R1-1, R2-2, R4-3), (A2, B3, R1-1, R2-2, R4- 4), (A2, B3, R1-1, R2-2, R4-5), (A2, B3, R1-1, R2-3, R4-1), (A2, B3, R1-1, R2-) 3, R4-2), (A2, B3, R1-1, R2-3, R4-3), (A2, B3, R1-1, R2-3, R4-4), (A2, B3, R1- 1, R2-3, R4-5), (A2, B3, R1-1, R2-4, R4-1), (A2, B3, R1-1, R2-4, R4-2), (A2, B3, R1-1, R2-4, R4-3), (A2, B3, R1-1, R2-4, R4-4), (A2, B3, R1-1, R2-4, R4-5) (A2, B3, R1-1, R2-5, R4-1), (A2, B3, R1-1, R2-5, R4-2), (A2, B3, R1-1, R2-5, R4-3), (A2, B3, R1-1, R2-5, R4-4), (A2, B3, R1-1, R2-5, R4-5), (A2, B3, R1-2, R2-1, R4-1), (A2, B3, R1-2, R2-1, R4-2), (A2, B3, R1-2, R2-1, R4-3), (A2, B3, R1-2, R2-1, R4-4), (A2, B3, R1-2, R2-1, R4-5), (A2, B3, R1-2, R2-2, R4-1), ( A2, B3, R1-2, R2-2, R4-2), (A2, B3, R1-2, R2-2, R4-3), (A2, B3, R1-2, R2-2, R4-2) 4), (A2, B3, R1-2, R2-2, R4-5) (A2, B3, R1-2, R2-3, R4-1), (A2, B3, R1-2, R2-3, R4-2), (A2, B3, R1-2, R2-3, R4 -3), (A2, B3, R1-2, R2-3, R4-4), (A2, B3, R1-2, R2-3, R4-5), (A2, B3, R1-2, R2 -4, R4-1), (A2, B3, R1-2, R2-4, R4-2), (A2, B3, R1-2, R2-4, R4-3), (A2, B3, R1) -2, R2-4, R4-4), (A2, B3, R1-2, R2-4, R4-5), (A2, B3, R1-2, R2-5, R4-1), (A2 , B3, R1-2, R2-5, R4-2), (A2, B3, R1-2, R2-5, R4-3), (A2, B3, R1-2, R2-5, R4-4) ), (A2, B3, R1-2, R2-5, R4-5), (A2, B3, R1-3, R2-1, R4-1), (A2, B3, R1-3, R2-1) , R4-2), (A2, B3, R1-3, R2-1, R4-3), (A2, B3, R1-3, R2-1, R4-4), (A2, B3, R1-3) , R2-1, R4-5), (A2, B3, R1-3, R2-2, R4-1), (A2, B3, R1-3, R2-2, R4-2), (A2, B3) , R1-3, R2-2, R4-3), (A2, B3, R1-3, R2-2, R4-4), (A2, B3, R1-3, R2-2, R4-5), (A2, B3, R1-3, R2-3, R4-1), (A2, B3, R1-3, R2-3, R4-2), (A2, B3, R1-3, R2-3, R4 -3), (A2, B3, R1-3, R2-3, R4-4), (A2, B3, R1-3, R2-3, R4-5), (A2, B3, R1-3, R2 -4, R4-1), (A2, B3, R1-3, R2-4, R4-2), (A2, B3, R1-3, R2-4, R4-3), (A2, B3, R1) -3, R2-4, R4-4), (A2, B3, R1-3 , R2-4, R4-5), (A2, B3, R1-3, R2-5, R4-1), (A2, B3, R1-3, R2-5, R4-2), (A2, B3) , R1-3, R2-5, R4-3), (A2, B3, R1-3, R2-5, R4-4), (A2, B3, R1-3, R2-5, R4-5), (A2, B4, R1-1, R2-1, R4-1), (A2, B4, R1-1, R2-1, R4-2), (A2, B4, R1-1, R2-1, R4 -3), (A2, B4, R1-1, R2-1, R4-4), (A2, B4, R1-1, R2-1, R4-5), (A2, B4, R1-1, R2 -2, R4-1), (A2, B4, R1-1, R2-2, R4-2), (A2, B4, R1-1, R2-2, R4-3), (A2, B4, R1) -1, R2-2, R4-4), (A2, B4, R1-1, R2-2, R4-5), (A2, B4, R1-1, R2-3, R4-1), (A2 , B4, R1-1, R2-3, R4-2), (A2, B4, R1-1, R2-3, R4-3), (A2, B4, R1-1, R2-3, R4-4) ), (A2, B4, R1-1, R2-3, R4-5), (A2, B4, R1-1, R2-4, R4-1), (A2, B4, R1-1, R2-4) , R4-2), (A2, B4, R1-1, R2-4, R4-3), (A2, B4, R1-1, R2-4, R4-4), (A2, B4, R1-1) , R2-4, R4-5), (A2, B4, R1-1, R2-5, R4-1), (A2, B4, R1-1, R2-5, R4-2), (A2, B4) , R1-1, R2-5, R4-3), (A2, B4, R1-1, R2-5, R4-4), (A2, B4, R1-1, R2-5, R4-5), (A2, B4, R1-2, R2-1, R4-1), (A2, B4, R1-2, R2-1, R4-2), (A2, B4, R1-2, R2-1, R4 -3), (A2, B4, R1-2, R2-1, R4-4) (A2, B4, R1-2, R2-1, R4-5), (A2, B4, R1-2, R2-2, R4-1), (A2, B4, R1-2, R2-2, R4 -2), (A2, B4, R1-2, R2-2, R4-3), (A2, B4, R1-2, R2-2, R4-4), (A2, B4, R1-2, R2 -2, R4-5), (A2, B4, R1-2, R2-3, R4-1), (A2, B4, R1-2, R2-3, R4-2), (A2, B4, R1) -2, R2-3, R4-3), (A2, B4, R1-2, R2-3, R4-4), (A2, B4, R1-2, R2-3, R4-5), (A2 , B4, R1-2, R2-4, R4-1), (A2, B4, R1-2, R2-4, R4-2), (A2, B4, R1-2, R2-4, R4-3) ), (A2, B4, R1-2, R2-4, R4-4), (A2, B4, R1-2, R2-4, R4-5), (A2, B4, R1-2, R2-5) , R4-1), (A2, B4, R1-2, R2-5, R4-2), (A2, B4, R1-2, R2-5, R4-3), (A2, B4, R1-2) , R2-5, R4-4), (A2, B4, R1-2, R2-5, R4-5), (A2, B4, R1-3, R2-1, R4-1), (A2, B4) , R1-3, R2-1, R4-2), (A2, B4, R1-3, R2-1, R4-3), (A2, B4, R1-3, R2-1, R4-4), (A2, B4, R1-3, R2-1, R4-5), (A2, B4, R1-3, R2-2, R4-1), (A2, B4, R1-3, R2-2, R4 -2), (A2, B4, R1-3, R2-2, R4-3), (A2, B4, R1-3, R2-2, R4-4), (A2, B4, R1-3, R2 -2, R4-5), (A2, B4, R1-3, R2-3, R4-1), (A2, B4, R1-3, R2-3, R4-2), (A2, B4, R1) -3, R2-3, R4-3), (A2, B4, R1- 3, R2-3, R4-4), (A2, B4, R1-3, R2-3, R4-5), (A2, B4, R1-3, R2-4, R4-1), (A2, B4, R1-3, R2-4, R4-2), (A2, B4, R1-3, R2-4, R4-3), (A2, B4, R1-3, R2-4, R4-4) (A2, B4, R1-3, R2-4, R4-5), (A2, B4, R1-3, R2-5, R4-1), (A2, B4, R1-3, R2-5, R4-2), (A2, B4, R1-3, R2-5, R4-3), (A2, B4, R1-3, R2-5, R4-4), (A2, B4, R1-3, R2-5, R4-5), (A2, B5, R1-1, R2-1, R4-1), (A2, B5, R1-1, R2-1, R4-2), (A2, B5, R1-1, R2-1, R4-3), (A2, B5, R1-1, R2-1, R4-4), (A2, B5, R1-1, R2-1, R4-5), A2, B5, R1-1, R2-2, R4-1), (A2, B5, R1-1, R2-2, R4-2), (A2, B5, R1-1, R2-2, R4-) 3), (A2, B5, R1-1, R2-2, R4-4), (A2, B5, R1-1, R2-2, R4-5), (A2, B5, R1-1, R2-) 3, R4-1), (A2, B5, R1-1, R2-3, R4-2), (A2, B5, R1-1, R2-3, R4-3), (A2, B5, R1-) 1, R2-3, R4-4), (A2, B5, R1-1, R2-3, R4-5), (A2, B5, R1-1, R2-4, R4-1), (A2, B5, R1-1, R2-4, R4-2), (A2, B5, R1-1, R2-4, R4-3), (A2, B5, R1-1, R2-4, R4-4) (A2, B5, R1-1, R2-4, R4-5), (A2, B5, R1-1, R2-5, R4-1), (A2, B5, R1-1, R2-5, R4-2), (A2, B5, R1-1, R2-5, R4-3) (A2, B5, R1-1, R2-5, R4-4), (A2, B5, R1-1, R2-5, R4-5), (A2, B5, R1-2, R2-1, R4-1), (A2, B5, R1-2, R2-1, R4-2), (A2, B5, R1-2, R2-1, R4-3), (A2, B5, R1-2, R2-1, R4-4), (A2, B5, R1-2, R2-1, R4-5), (A2, B5, R1-2, R2-2, R4-1), (A2, B5, R1-2, R2-2, R4-2), (A2, B5, R1-2, R2-2, R4-3), (A2, B5, R1-2, R2-2, R4-4), ( A2, B5, R1-2, R2-2, R4-5), (A2, B5, R1-2, R2-3, R4-1), (A2, B5, R1-2, R2-3, R4-) 2), (A2, B5, R1-2, R2-3, R4-3), (A2, B5, R1-2, R2-3, R4-4), (A2, B5, R1-2, R2-) 3, R4-5), (A2, B5, R1-2, R2-4, R4-1), (A2, B5, R1-2, R2-4, R4-2), (A2, B5, R1-) 2, R2-4, R4-3), (A2, B5, R1-2, R2-4, R4
-4), (A2, B5, R1-2, R2-4, R4-5), (A2, B5, R1-2, R2-5, R4-1), (A2, B5, R1-2, R2 -5, R4-2), (A2, B5, R1-2, R2-5, R4-3), (A2, B5, R1-2, R2-5, R4-4), (A2, B5, R1) -2, R2-5, R4-5), (A2, B5, R1-3, R2-1, R4-1), (A2, B5, R1-3, R2-1, R4-2), (A2 , B5, R1-3, R2-1, R4-3), (A2, B5, R1-3, R2-1, R4-4), (A2, B5, R1-3, R2-1, R4-5) ), (A2, B5, R1-3, R2-2, R4-1), (A2, B5, R1-3, R2-2, R4-2), (A2, B5, R1-3, R2-2) , R4-3), (A2, B5, R1-3, R2-2, R4-4), (A2, B5, R1-3, R2-2, R4-5), (A2, B5, R1-3) , R2-3, R4-1), (A2, B5, R1-3, R2-3, R4-2), (A2, B5, R1-3, R2-3, R4-3), (A2, B5) , R1-3, R2-3, R4-4), (A2, B5, R1-3, R2-3, R4-5), (A2, B5, R1-3, R2-4, R4-1), (A2, B5, R1-3, R2-4, R4-2), (A2, B5, R1-3, R2-4, R4-3), (A2, B5, R1-3, R2-4, R4 -4), (A2, B5, R1-3, R2-4, R4-5), (A2, B5, R1-3, R2-5, R4-1), (A2, B5, R1-3, R2 -5, R4-2), (A2, B5, R1-3, R2-5, R4-3), (A2, B5, R1-3, R2-5, R4-4), (A2, B5, R1) -3, R2-5, R4-5), (A2, B6, R1-1, R2-1, R4-1), (A2, B6, R1-1, R2-1, R4-2), (A2 , B6, R1-1, R2-1, R4-3), (A2, B6, R1-1, R2-1, R4-4), (A2, B6, R1-1, R2-1, R4-5), (A2, B6, R1-1, R2-2, R4-1), ( A2, B6, R1-1, R2-2, R4-2), (A2, B6, R1-1, R2-2, R4-3), (A2, B6, R1-1, R2-2, R4-) 4), (A2, B6, R1-1, R2-2, R4-5), (A2, B6, R1-1, R2-3, R4-1), (A2, B6, R1-1, R2-) 3, R4-2), (A2, B6, R1-1, R2-3, R4-3), (A2, B6, R1-1, R2-3, R4-4), (A2, B6, R1-) 1, R2-3, R4-5), (A2, B6, R1-1, R2-4, R4-1), (A2, B6, R1-1, R2-4, R4-2), (A2, B6, R1-1, R2-4, R4-3), (A2, B6, R1-1, R2-4, R4-4), (A2, B6, R1-1, R2-4, R4-5) (A2, B6, R1-1, R2-5, R4-1), (A2, B6, R1-1, R2-5, R4-2), (A2, B6, R1-1, R2-5, R4-3), (A2, B6, R1-1, R2-5, R4-4), (A2, B6, R1-1, R2-5, R4-5), (A2, B6, R1-2, R2-1, R4-1), (A2, B6, R1-2, R2-1, R4-2), (A2, B6, R1-2, R2-1, R4-3), (A2, B6, R1-2, R2-1, R4-4), (A2, B6, R1-2, R2-1, R4-5), (A2, B6, R1-2, R2-2, R4-1), ( A2, B6, R1-2, R2-2, R4-2), (A2, B6, R1-2, R2-2, R4-3), (A2, B6, R1-2, R2-2, R4-2) 4), (A2, B6, R1-2, R2-2, R4-5), (A2, B6, R1-2, R2-3, R4-1), (A2, B6, R1-2, R2-) 3, R4-2), (A2, B6, R1-2, R2-3, R 4-3), (A2, B6, R1-2, R2-3, R4-4), (A2, B6, R1-2, R2-3, R4-5), (A2, B6, R1-2, R2-4, R4-1), (A2, B6, R1-2, R2-4, R4-2), (A2, B6, R1-2, R2-4, R4-3), (A2, B6, R1-2, R2-4, R4-4), (A2, B6, R1-2, R2-4, R4-5), (A2, B6, R1-2, R2-5, R4-1), ( A2, B6, R1-2, R2-5, R4-2), (A2, B6, R1-2, R2-5, R4-3), (A2, B6, R1-2, R2-5, R4-) 4), (A2, B6, R1-2, R2-5, R4-5), (A2, B6, R1-3, R2-1, R4-1), (A2, B6, R1-3, R2-) 1, R4-2), (A2, B6, R1-3, R2-1, R4-3), (A2, B6, R1-3, R2-1, R4-4), (A2, B6, R1-) 3, R2-1, R4-5), (A2, B6, R1-3, R2-2, R4-1), (A2, B6, R1-3, R2-2, R4-2), (A2, B6, R1-3, R2-2, R4-3), (A2, B6, R1-3, R2-2, R4-4), (A2, B6, R1-3, R2-2, R4-5) (A2, B6, R1-3, R2-3, R4-1), (A2, B6, R1-3, R2-3, R4-2), (A2, B6, R1-3, R2-3, R4-3), (A2, B6, R1-3, R2-3, R4-4), (A2, B6, R1-3, R2-3, R4-5), (A2, B6, R1-3, R2-4, R4-1), (A2, B6, R1-3, R2-4, R4-2), (A2, B6, R1-3, R2-4, R4-3), (A2, B6, R1-3, R2-4, R4-4), (A2, B6, R1-3, R2-4, R4-5), (A2, B6, R1-3, R2-5, R4-1), ( A2, B6, R1-3, R2-5, R4-2), (A2, B6) , R1-3, R2-5, R4-3), (A2, B6, R1-3, R2-5, R4-4), (A2, B6, R1-3, R2-5, R4-5), (A2, B7, R1-1, R2-1, R4-1), (A2, B7, R1-1, R2-1, R4-2), (A2, B7, R1-1, R2-1, R4 -3), (A2, B7, R1-1, R2-1, R4-4), (A2, B7, R1-1, R2-1, R4-5), (A2, B7, R1-1, R2 -2, R4-1), (A2, B7, R1-1, R2-2, R4-2), (A2, B7, R1-1, R2-2, R4-3), (A2, B7, R1) -1, R2-2, R4-4), (A2, B7, R1-1, R2-2, R4-5), (A2, B7, R1-1, R2-3, R4-1), (A2 , B7, R1-1, R2-3, R4-2), (A2, B7, R1-1, R2-3, R4-3), (A2, B7, R1-1, R2-3, R4-4) ), (A2, B7, R1-1, R2-3, R4-5), (A2, B7, R1-1, R2-4, R4-1), (A2, B7, R1-1, R2-4) , R4-2), (A2, B7, R1-1, R2-4, R4-3), (A2, B7, R1-1, R2-4, R4-4), (A2, B7, R1-1) , R2-4, R4-5), (A2, B7, R1-1, R2-5, R4-1), (A2, B7, R1-1, R2-5, R4-2), (A2, B7) , R1-1, R2-5, R4-3), (A2, B7, R1-1, R2-5, R4-4), (A2, B7, R1-1, R2-5, R4-5), (A2, B7, R1-2, R2-1, R4-1), (A2, B7, R1-2, R2-1, R4-2), (A2, B7, R1-2, R2-1, R4 -3), (A2, B7, R1-2, R2-1, R4-4), (A2, B7, R1-2, R2-1, R4-5), (A2, B7, R1-2, R2) -2, R4-1), (A2, B7, R1-2, R2-2, R4-2), (A2, B7, R1-2, R2-2, R4-3), (A2, B7, R1-2, R2-2, R4-4), (A2, B7, R1-2, R2-2, R4-5), (A2, B7, R1-2, R2-3, R4-1), (A2, B7, R1-2, R2-3, R4-2), (A2, B7, R1-2, R2-3, R4-3), (A2, B7, R1-2, R2-3, R4-4), (A2, B7, R1-2, R2-3, R4-5), ( A2, B7, R1-2, R2-4, R4-1), (A2, B7, R1-2, R2-4, R4-2), (A2, B7, R1-2, R2-4, R4-) 3), (A2, B7, R1-2, R2-4, R4-4), (A2, B7, R1-2, R2-4, R4-5), (A2, B7, R1-2, R2-) 5, R4-1), (A2, B7, R1-2, R2-5, R4-2), (A2, B7, R1-2, R2-5, R4-3), (A2, B7, R1-) 2, R2-5, R4-4), (A2, B7, R1-2, R2-5, R4-5), (A2, B7, R1-3, R2-1, R4-1), (A2, B7, R1-3, R2-1, R4-2), (A2, B7, R1-3, R2-1, R4-3), (A2, B7, R1-3, R2-1, R4-4) (A2, B7, R1-3, R2-1, R4-5), (A2, B7, R1-3, R2-2, R4-1), (A2, B7, R1-3, R2-2, R4-2), (A2, B7, R1-3, R2-2, R4-3), (A2, B7, R1-3, R2-2, R4-4), (A2, B7, R1-3, R2-2, R4-5), (A2, B7, R1-3, R2-3, R4-1), (A2, B7, R1-3, R2-3, R4-2), (A2, B7, R1-3, R2-3, R4-3), (A2, B7, R1-3, R2-3, R4-4), (A2, B7, R1-3, R2-3, R4-5), ((2) A2, B7, R1-3, R2-4, R4-1), (A2, B 7, R1-3, R2-4, R4-2), (A2, B7, R1-3, R2-4, R4-3), (A2, B7, R1-3, R2-4, R4-4) (A2, B7, R1-3, R2-4, R4-5), (A2, B7, R1-3, R2-5, R4-1), (A2, B7, R1-3, R2-5, R4-2), (A2, B7, R1-3, R2-5, R4-3), (A2, B7, R1-3, R2-5, R4-4), (A2, B7, R1-3, R2-5, R4-5), (A2, B8, R1-1, R2-1, R4-1), (A2, B8, R1-1, R2-1, R4-2), (A2, B8, R1-1, R2-1, R4-3), (A2, B8, R1-1, R2-1, R4-4), (A2, B8, R1-1, R2-1, R4-5), A2, B8, R1-1, R2-2, R4-1), (A2, B8, R1-1, R2-2, R4-2), (A2, B8, R1-1, R2-2, R4-) 3), (A2, B8, R1-1, R2-2, R4-4), (A2, B8, R1-1, R2-2, R4-5), (A2, B8, R1-1, R2-) 3, R4-1), (A2, B8, R1-1, R2-3, R4-2), (A2, B8, R1-1, R2-3, R4-3), (A2, B8, R1-) 1, R2-3, R4-4), (A2, B8, R1-1, R2-3, R4-5), (A2, B8, R1-1, R2-4, R4-1), (A2, B8, R1-1, R2-4, R4-2), (A2, B8, R1-1, R2-4, R4-3), (A2, B8, R1-1, R2-4, R4-4) (A2, B8, R1-1, R2-4, R4-5), (A2, B8, R1-1, R2-5, R4-1), (A2, B8, R1-1, R2-5, R4-2), (A2, B8, R1-1, R2-5, R4-3), (A2, B8, R1-1, R2-5, R4-4), (A2, B8, R1-1, R2-5, R4-5), (A2, B8, R1-2, R2-1, R4-1), (A2, B8, R1-2, R2-1, R4-2), (A2, B8, R1-2, R2-1, R4-3), (A2, B8, R1-2, R2-1, R4-4), (A2, B8, R1-2, R2-1, R4-5), (A2, B8, R1-2, R2-2, R4-1), (A2, B8, R1-2, R2-2, R4-2), (A2, B8, R1-2, R2-2, R4-3), (A2, B8, R1-2, R2-2, R4-4), ( A2, B8, R1-2, R2-2, R4-5), (A2, B8, R1-2, R2-3, R4-1), (A2, B8, R1-2, R2-3, R4-) 2), (A2, B8, R1-2, R2-3, R4-3), (A2, B8, R1-2, R2-3, R4-4), (A2, B8, R1-2, R2-) 3, R4-5), (A2, B8, R1-2, R2-4, R4-1), (A2, B8, R1-2, R2-4, R4-2), (A2, B8, R1-) 2, R2-4, R4-3), (A2, B8, R1-2, R2-4, R4-4), (A2, B8, R1-2, R2-4, R4-5), (A2, B8, R1-2, R2-5, R4-1), (A2, B8, R1-2, R2-5, R4-2), (A2, B8, R1-2, R2-5, R4-3) (A2, B8, R1-2, R2-5, R4-4), (A2, B8, R1-2, R2-5, R4-5), (A2, B8, R1-3, R2-1, R4-1), (A2, B8, R1-3, R2-1, R4-2), (A2, B8, R1-3, R2-1, R4-3), (A2, B8, R1-3, R2-1, R4-4), (A2, B8, R1-3, R2-1, R4-5), (A2, B8, R1-3, R2-2, R4-1), (A2, B8, R1-3, R2-2, R4-2), (A2, B8, R1-3, R2-2, R4-3), (A2, B8, R1-3, R2-2, R4-4), ( A2, B8, R1-3, R2-2, R4-5), (A2, B2) B8, R1-3, R2-3, R4-1), (A2, B8, R1-3, R2-3, R4-2), (A2, B8, R1-3, R2-3, R4-3) (A2, B8, R1-3, R2-3, R4-4), (A2, B8, R1-3, R2-3, R4-5), (A2, B8, R1-3, R2-4, R4-1), (A2, B8, R1-3, R2-4, R4-2), (A2, B8, R1-3, R2-4, R4-3), (A2, B8, R1-3, R2-4, R4-4), (A2, B8, R1-3, R2-4, R4-5), (A2, B8, R1-3, R2-5, R4-1), (A2, B8, R1-3, R2-5, R4-2), (A2, B8, R1-3, R2-5, R4-3), (A2, B8, R1-3, R2-5, R4-4), ( A2, B8, R1-3, R2-5, R4-5), (A2, B9, R1-1, R2-1, R4-1), (A2, B9, R1-1, R2-1, R4-) 2), (A2, B9, R1-1, R2-1, R4-3), (A2, B9, R1-1, R2-1, R4-4), (A2, B9, R1-1, R2- 1, R4-5), (A2, B9, R1-1, R2-2, R4-1), (A2, B9, R1-1, R2-2, R4-2), (A2, B9, R1-) 1, R2-2, R4-3), (A2, B9, R1-1, R2-2, R4-4), (A2, B9, R1-1, R2-2, R4-5), (A2, B9, R1-1, R2-3, R4-1), (A2, B9, R1-1, R2-3, R4-2), (A2, B9, R1-1, R2-3, R4-3) (A2, B9, R1-1, R2-3, R4-4), (A2, B9, R1-1, R2-3, R4-5), (A2, B9, R1-1, R2-4, R4-1), (A2, B9, R1-1, R2-4, R4-2), (A2, B9, R1-1, R2-4, R4-3), (A2, B9, R1-1, R2-4, R4-4), (A2, B9, R1-1, R2-4) , R4-5), (A2, B9, R1-1, R2-5, R4-1), (A2, B9, R1-1, R2-5, R4-2), (A2, B9, R1-1) , R2-5, R4-3), (A2, B9, R1-1, R2-5, R4-4), (A2, B9, R1-1, R2-5, R4-5), (A2, B9) , R1-2, R2-1, R4-1), (A2, B9, R1-2, R2-1, R4-2), (A2, B9, R1-2, R2-1, R4-3), (A2, B9, R1-2, R2-1, R4-4), (A2, B9, R1-2, R2-1, R4-5), (A2, B9, R1-2, R2-2, R4 -1), (A2, B9, R1-2, R2-2, R4-2), (A2, B9, R1-2, R2-2, R4-3), (A2, B9, R1-2, R2) -2, R4-4), (A2, B9, R1-2, R2-2, R4-5), (A2, B9, R1-2, R2-3, R4-1), (A2, B9, R1) -2, R2-3, R4-2), (A2, B9, R1-2, R2-3, R4-3), (A2, B9, R1-2, R2-3, R4-4), (A2 , B9, R1-2, R2-3, R4-5), (A2, B9, R1-2, R2-4, R4-1), (A2, B9, R1-2, R2-4, R4-2) ), (A2, B9, R1-2, R2-4, R4-3), (A2, B9, R1-2, R2-4, R4-4), (A2, B9, R1-2, R2-4) , R4-5), (A2, B9, R1-2, R2-5, R4-1), (A2, B9, R1-2, R2-5, R4-2), (A2, B9, R1-2) , R2-5, R4-3), (A2, B9, R1-2, R2-5, R4-4), (A2, B9, R1-2, R2-5, R4-5), (A2, B9) , R1-3, R2-1, R4-1), (A2, B9, R1-3, R2-1, R4-2), (A2, B9, R1-3, R2-1, R4-3), (A2, B9, R1-3, R2-1, R4-4), (A2, B2 B9, R1-3, R2-1, R4-5), (A2, B9, R1-3, R2-2, R4-1), (A2, B9, R1-3, R2-2, R4-2) (A2, B9, R1-3, R2-2, R4-3), (A2, B9, R1-3, R2-2, R4-4), (A2, B9, R1-3, R2-2, R4-5), (A2, B9, R1-3, R2-3, R4-1), (A2, B9, R1-3, R2-3, R4-2), (A2, B9, R1-3, R2-3, R4-3), (A2, B9, R1-3, R2-3, R4-4), (A2, B9, R1-3, R2-3, R4-5), (A2, B9, R1-3, R2-4, R4-1), (A2, B9, R1-3, R2-4, R4-2), (A2, B9, R1-3, R2-4, R4-3), ( A2, B9, R1-3, R2-4, R4-4), (A2, B9, R1-3, R2-4, R4-5), (A2, B9, R1-3, R2-5, R4-) 1), (A2, B9, R1-3, R2-5, R4-2), (A2, B9, R1-3, R2-5, R4-3), (A2, B9, R1-3, R2-) 5, R4-4), (A2, B9, R1-3, R2-5, R4-5), (A2, B10, R1-1, R2-1, R4-1), (A2, B10, R1-) 1, R2-1, R4-2), (A2, B10, R1-1, R2-1, R4-3), (A2, B10, R1-1, R2-1, R4-4), (A2, B10, R1-1, R2-1, R4-5), (A2, B10, R1-1, R2-2, R4-1), (A2, B10, R1-1, R2-2, R4-2) (A2, B10, R1-1, R2-2, R4-3), (A2, B10, R1-1, R2-2, R4-4), (A2, B10, R1-1, R2-2, R4-5), (A2, B10, R1-1, R2-3, R4-1), (A2, B10, R1-1, R2-3, R4-2), (A2, B10, R1-1, R2-3, R4-3), (A2, B10, R1-1, R2-3, R4-4), (A2, B10, R1-1, R2-3, R4-5), (A2, B10, R1-1, R2-4, R4-1) (A2, B10, R1-1, R2-4, R4-2), (A2, B10, R1-1, R2-4, R4-3), (A2, B10, R1-1, R2-4, R4-4), (A2, B10, R1-1, R2-4, R4-5), (A2, B10, R1-1, R2-5, R4-1), (A2, B10, R1-1, R2-5, R4-2), (A2, B10, R1-1, R2-5, R4-3), (A2, B10, R1-1, R2-5, R4-4), (A2, B10, R1-1, R2-5, R4-5), (A2, B10, R1-2, R2-1, R4-1), (A2, B10, R1-2, R2-1, R4-2), ( A2, B10, R1-2, R2-1, R4-3), (A2, B10, R1-2, R2-1, R4-4), (A2, B10, R1-2, R2-1, R4-, 5), (A2, B10, R1-2, R2-2, R4-1), (A2, B10, R1-2, R2-2, R4-2), (A2, B10, R1-2, R2-) 2, R4-3), (A2, B10, R
1-2, R2-2, R4-4), (A2, B10, R1-2, R2-2, R4-5), (A2, B10, R1-2, R2-3, R4-1), ( A2, B10, R1-2, R2-3, R4-2), (A2, B10, R1-2, R2-3, R4-3), (A2, B10, R1-2, R2-3, R4-) 4), (A2, B10, R1-2, R2-3, R4-5), (A2, B10, R1-2, R2-4, R4-1), (A2, B10, R1-2, R2-) 4, R4-2), (A2, B10, R1-2, R2-4, R4-3), (A2, B10, R1-2, R2-4, R4-4), (A2, B10, R1-) 2, R2-4, R4-5), (A2, B10, R1-2, R2-5, R4-1), (A2, B10, R1-2, R2-5, R4-2), (A2, B10, R1-2, R2-5, R4-3), (A2, B10, R1-2, R2-5, R4-4), (A2, B10, R1-2, R2-5, R4-5) (A2, B10, R1-3, R2-1, R4-1), (A2, B10, R1-3, R2-1, R4-2), (A2, B10, R1-3, R2-1, R4-3), (A2, B10, R1-3, R2-1, R4-4), (A2, B10, R1-3, R2-1, R4-5), (A2, B10, R1-3, R2-2, R4-1), (A2, B10, R1-3, R2-2, R4-2), (A2, B10, R1-3, R2-2, R4-3), (A2, B10, R1-3, R2-2, R4-4), (A2, B10, R1-3, R2-2, R4-5), (A2, B10, R1-3, R2-3, R4-1), ( A2, B10, R1-3, R2-3, R4-2), (A2, B10, R1-3, R2-3, R4-3), (A2, B10, R1-3, R2-3, R4-) 4), (A2, B10, R1-3, R2-3, R4-5), (A2, B10, R1-3, R2-4, R4-1), (A2, B10, R1-3, R2-) Four, R4-2), (A2, B10, R1-3, R2-4, R4-3), (A2, B10, R1-3, R2-4, R4-4), (A2, B10, R1-3, R2-4, R4-5), (A2, B10, R1-3, R2-5, R4-1), (A2, B10, R1-3, R2-5, R4-2), (A2, B10, R1-3, R2-5, R4-3), (A2, B10, R1-3, R2-5, R4-4), (A2, B10, R1-3, R2-5, R4-5).

(C, B, R1) = (C1, B1, R1-1)、(C1, B1, R1-2)、(C1, B1, R1-3)、(C1, B2, R1-1)、(C1, B2, R1-2)、(C1, B2, R1-3)、(C1, B3, R1-1)、(C1, B3, R1-2)、(C1, B3, R1-3)、(C1, B4, R1-1)、(C1, B4, R1-2)、(C1, B4, R1-3)、(C1, B5, R1-1)、(C1, B5, R1-2)、(C1, B5, R1-3)、(C1, B6, R1-1)、(C1, B6, R1-2)、(C1, B6, R1-3)、(C1, B7, R1-1)、(C1, B7, R1-2)、(C1, B7, R1-3)、(C1, B8, R1-1)、(C1, B8, R1-2)、(C1, B8, R1-3)、(C1, B9, R1-1)、(C1, B9, R1-2)、(C1, B9, R1-3)、(C1, B10, R1-1)、(C1, B10, R1-2)、(C1, B10, R1-3)、(C2, B1, R1-1)、(C2, B1, R1-2)、(C2, B1, R1-3)、(C2, B2, R1-1)、(C2, B2, R1-2)、(C2, B2, R1-3)、(C2, B3, R1-1)、(C2, B3, R1-2)、(C2, B3, R1-3)、(C2, B4, R1-1)、(C2, B4, R1-2)、(C2, B4, R1-3)、(C2, B5, R1-1)、(C2, B5, R1-2)、(C2, B5, R1-3)、(C2, B6, R1-1)、(C2, B6, R1-2)、(C2, B6, R1-3)、(C2, B7, R1-1)、(C2, B7, R1-2)、(C2, B7, R1-3)、(C2, B8, R1-1)、(C2, B8, R1-2)、(C2, B8, R1-3)、(C2, B9, R1-1)、(C2, B9, R1-2)、(C2, B9, R1-3)、(C2, B10, R1-1)、(C2, B10, R1-2)、(C2, B10, R1-3)、(C3, B1, R1-1)、(C3, B1, R1-2)、(C3, B1, R1-3)、(C3, B2, R1-1)、(C3, B2, R1-2)、(C3, B2, R1-3)、(C3, B3, R1-1)、(C3, B3, R1-2)、(C3, B3, R1-3)、(C3, B4, R1-1)、(C3, B4, R1-2)、(C3, B4, R1-3)、(C3, B5, R1-1)、(C3, B5, R1-2)、(C3, B5, R1-3)、(C3, B6, R1-1)、(C3, B6, R1-2)、(C3, B6, R1-3)、(C3, B7, R1-1)、(C3, B7, R1-2)、(C3, B7, R1-3)、(C3, B8, R1-1)、(C3, B8, R1-2)、(C3, B8, R1-3)、(C3, B9, R1-1)、(C3, B9, R1-2)、(C3, B9, R1-3)、(C3, B10, R1-1)、(C3, B10, R1-2)、(C3, B10, R1-3)、(C4, B1, R1-1)、(C4, B1, R1-2)、(C4, B1, R1-3)、(C4, B2, R1-1)、(C4, B2, R1-2)、(C4, B2, R1-3)、(C4, B3, R1-1)、(C4, B3, R1-2)、(C4, B3, R1-3)、(C4, B4, R1-1)、(C4, B4, R1-2)、(C4, B4, R1-3)、(C4, B5, R1-1)、(C4, B5, R1-2)、(C4, B5, R1-3)、(C4, B6, R1-1)、(C4, B6, R1-2)、(C4, B6, R1-3)、(C4, B7, R1-1)、(C4, B7, R1-2)、(C4, B7, R1-3)、(C4, B8, R1-1)、(C4, B8, R1-2)、(C4, B8, R1-3)、(C4, B9, R1-1)、(C4, B9, R1-2)、(C4, B9, R1-3)、(C4, B10, R1-1)、(C4, B10, R1-2)、(C4, B10, R1-3)、(C5, B1, R1-1)、(C5, B1, R1-2)、(C5, B1, R1-3)、(C5, B2, R1-1)、(C5, B2, R1-2)、(C5, B2, R1-3)、(C5, B3, R1-1)、(C5, B3, R1-2)、(C5, B3, R1-3)、(C5, B4, R1-1)、(C5, B4, R1-2)、(C5, B4, R1-3)、(C5, B5, R1-1)、(C5, B5, R1-2)、(C5, B5, R1-3)、(C5, B6, R1-1)、(C5, B6, R1-2)、(C5, B6, R1-3)、(C5, B7, R1-1)、(C5, B7, R1-2)、(C5, B7, R1-3)、(C5, B8, R1-1)、(C5, B8, R1-2)、(C5, B8, R1-3)、(C5, B9, R1-1)、(C5, B9, R1-2)、(C5, B9, R1-3)、(C5, B10, R1-1)、(C5, B10, R1-2)、(C5, B10, R1-3)、(C6, B1, R1-1)、(C6, B1, R1-2)、(C6, B1, R1-3)、(C6, B2, R1-1)、(C6, B2, R1-2)、(C6, B2, R1-3)、(C6, B3, R1-1)、(C6, B3, R1-2)、(C6, B3, R1-3)、(C6, B4, R1-1)、(C6, B4, R1-2)、(C6, B4, R1-3)、(C6, B5, R1-1)、(C6, B5, R1-2)、(C6, B5, R1-3)、(C6, B6, R1-1)、(C6, B6, R1-2)、(C6, B6, R1-3)、(C6, B7, R1-1)、(C6, B7, R1-2)、(C6, B7, R1-3)、(C6, B8, R1-1)、(C6, B8, R1-2)、(C6, B8, R1-3)、(C6, B9, R1-1)、(C6, B9, R1-2)、(C6, B9, R1-3)、(C6, B10, R1-1)、(C6, B10, R1-2)、(C6, B10, R1-3)、(C7, B1, R1-1)、(C7, B1, R1-2)、(C7, B1, R1-3)、(C7, B2, R1-1)、(C7, B2, R1-2)、(C7, B2, R1-3)、(C7, B3, R1-1)、(C7, B3, R1-2)、(C7, B3, R1-3)、(C7, B4, R1-1)、(C7, B4, R1-2)、(C7, B4, R1-3)、(C7, B5, R1-1)、(C7, B5, R1-2)、(C7, B5, R1-3)、(C7, B6, R1-1)、(C7, B6, R1-2)、(C7, B6, R1-3)、(C7, B7, R1-1)、(C7, B7, R1-2)、(C7, B7, R1-3)、(C7, B8, R1-1)、(C7, B8, R1-2)、(C7, B8, R1-3)、(C7, B9, R1-1)、(C7, B9, R1-2)、(C7, B9, R1-3)、(C7, B10, R1-1)、(C7, B10, R1-2)、(C7, B10, R1-3)、(C8, B1, R1-1)、(C8, B1, R1-2)、(C8, B1, R1-3)、(C8, B2, R1-1)、(C8, B2, R1-2)、(C8, B2, R1-3)、(C8, B3, R1-1)、(C8, B3, R1-2)、(C8, B3, R1-3)、(C8, B4, R1-1)、(C8, B4, R1-2)、(C8, B4, R1-3)、(C8, B5, R1-1)、(C8, B5, R1-2)、(C8, B5, R1-3)、(C8, B6, R1-1)、(C8, B6, R1-2)、(C8, B6, R1-3)、(C8, B7, R1-1)、(C8, B7, R1-2)、(C8, B7, R1-3)、(C8, B8, R1-1)、(C8, B8, R1-2)、(C8, B8, R1-3)、(C8, B9, R1-1)、(C8, B9, R1-2)、(C8, B9, R1-3)、(C8, B10, R1-1)、(C8, B10, R1-2)、(C8, B10, R1-3)、(C9, B1, R1-1)、(C9, B1, R1-2)、(C9, B1, R1-3)、(C9, B2, R1-1)、(C9, B2, R1-2)、(C9, B2, R1-3)、(C9, B3, R1-1)、(C9, B3, R1-2)、(C9, B3, R1-3)、(C9, B4, R1-1)、(C9, B4, R1-2)、(C9, B4, R1-3)、(C9, B5, R1-1)、(C9, B5, R1-2)、(C9, B5, R1-3)、(C9, B6, R1-1)、(C9, B6, R1-2)、(C9, B6, R1-3)、(C9, B7, R1-1)、(C9, B7, R1-2)、(C9, B7, R1-3)、(C9, B8, R1-1)、(C9, B8, R1-2)、(C9, B8, R1-3)、(C9, B9, R1-1)、(C9, B9, R1-2)、(C9, B9, R1-3)、(C9, B10, R1-1)、(C9, B10, R1-2)、(C9, B10, R1-3)、(C10, B1, R1-1)、(C10, B1, R1-2)、(C10, B1, R1-3)、(C10, B2, R1-1)、(C10, B2, R1-2)、(C10, B2, R1-3)、(C10, B3, R1-1)、(C10, B3, R1-2)、(C10, B3, R1-3)、(C10, B4, R1-1)、(C10, B4, R1-2)、(C10, B4, R1-3)、(C10, B5, R1-1)、(C10, B5, R1-2)、(C10, B5, R1-3)、(C10, B6, R1-1)、(C10, B6, R1-2)、(C10, B6, R1-3)、(C10, B7, R1-1)、(C10, B7, R1-2)、(C10, B7, R1-3)、(C10, B8, R1-1)、(C10, B8, R1-2)、(C10, B8, R1-3)、(C10, B9, R1-1)、(C10, B9, R1-2)、(C10, B9, R1-3)、(C10, B10, R1-1)、(C10, B10, R1-2)、(C10, B10, R1-3)、(C11, B1, R1-1)、(C11, B1, R1-2)、(C11, B1, R1-3)、(C11, B2, R1-1)、(C11, B2, R1-2)、(C11, B2, R1-3)、(C11, B3, R1-1)、(C11, B3, R1-2)、(C11, B3, R1-3)、(C11, B4, R1-1)、(C11, B4, R1-2)、(C11, B4, R1-3)、(C11, B5, R1-1)、(C11, B5, R1-2)、(C11, B5, R1-3)、(C11, B6, R1-1)、(C11, B6, R1-2)、(C11, B6, R1-3)、(C11, B7, R1-1)、(C11, B7, R1-2)、(C11, B7, R1-3)、(C11, B8, R1-1)、(C11, B8, R1-2)、(C11, B8, R1-3)、(C11, B9, R1-1)、(C11, B9, R1-2)、(C11, B9, R1-3)、(C11, B10, R1-1)、(C11, B10, R1-2)、(C11, B10, R1-3)、(C12, B1, R1-1)、(C12, B1, R1-2)、(C12, B1, R1-3)、(C12, B2, R1-1)、(C12, B2, R1-2)、(C12, B2, R1-3)、(C12, B3, R1-1)、(C12, B3, R1-2)、(C12, B3, R1-3)、(C12, B4, R1-1)、(C12, B4, R1-2)、(C12, B4, R1-3)、(C12, B5, R1-1)、(C12, B5, R1-2)、(C12, B5, R1-3)、(C12, B6, R1-1)、(C12, B6, R1-2)、(C12, B6, R1-3)、(C12, B7, R1-1)、(C12, B7, R1-2)、(C12, B7, R1-3)、(C12, B8, R1-1)、(C12, B8, R1-2)、(C12, B8, R1-3)、(C12, B9, R1-1)、(C12, B9, R1-2)、(C12, B9, R1-3)、(C12, B10, R1-1)、(C12, B10, R1-2)、(C12, B10, R1-3)、(C13, B1, R1-1)、(C13, B1, R1-2)、(C13, B1, R1-3)、(C13, B2, R1-1)、(C13, B2, R1-2)、(C13, B2, R1-3)、(C13, B3, R1-1)、(C13, B3, R1-2)、(C13, B3, R1-3)、(C13, B4, R1-1)、(C13, B4, R1-2)、(C13, B4, R1-3)、(C13, B5, R1-1)、(C13, B5, R1-2)、(C13, B5, R1-3)、(C13, B6, R1-1)、(C13, B6, R1-2)、(C13, B6, R1-3)、(C13, B7, R1-1)、(C13, B7, R1-2)、(C13, B7, R1-3)、(C13, B8, R1-1)、(C13, B8, R1-2)、(C13, B8, R1-3)、(C13, B9, R1-1)、(C13, B9, R1-2)、(C13, B9, R1-3)、(C13, B10, R1-1)、(C13, B10, R1-2)、(C13, B10, R1-3)、(C14, B1, R1-1)、(C14, B1, R1-2)、(C14, B1, R1-3)、(C14, B2, R1-1)、(C14, B2, R1-2)、(C14, B2, R1-3)、(C14, B3, R1-1)、(C14, B3, R1-2)、(C14, B3, R1-3)、(C14, B4, R1-1)、(C14, B4, R1-2)、(C14, B4, R1-3)、(C14, B5, R1-1)、(C14, B5, R1-2)、(C14, B5, R1-3)、(C14, B6, R1-1)、(C14, B6, R1-2)、(C14, B6, R1-3)、(C14, B7, R1-1)、(C14, B7, R1-2)、(C14, B7, R1-3)、(C14, B8, R1-1)、(C14, B8, R1-2)、(C14, B8, R1-3)、(C14, B9, R1-1)、(C14, B9, R1-2)、(C14, B9, R1-3)、(C14, B10, R1-1)、(C14, B10, R1-2)、(C14, B10, R1-3)、(C15, B1, R1-1)、(C15, B1, R1-2)、(C15, B1, R1-3)、(C15, B2, R1-1)、(C15, B2, R1-2)、(C15, B2, R1-3)、(C15, B3, R1-1)、(C15, B3, R1-2)、(C15, B3, R1-3)、(C15, B4, R1-1)、(C15, B4, R1-2)、(C15, B4, R1-3)、(C15, B5, R1-1)、(C15, B5, R1-2)、(C15, B5, R1-3)、(C15, B6, R1-1)、(C15, B6, R1-2)、(C15, B6, R1-3)、(C15, B7, R1-1)、(C15, B7, R1-2)、(C15, B7, R1-3)、(C15, B8, R1-1)、(C15, B8, R1-2)、(C15, B8, R1-3)、(C15, B9, R1-1)、(C15, B9, R1-2)、(C15, B9, R1-3)、(C15, B10, R1-1)、(C15, B10, R1-2)、(C15, B10, R1-3)、(C16, B1, R1-1)、(C16, B1, R1-2)、(C16, B1, R1-3)、(C16, B2, R1-1)、(C16, B2, R1-2)、(C16, B2, R1-3)、(C16, B3, R1-1)、(C16, B3, R1-2)、(C16, B3, R1-3)、(C16, B4, R1-1)、(C16, B4, R1-2)、(C16, B4, R1-3)、(C16, B5, R1-1)、(C16, B5, R1-2)、(C16, B5, R1-3)、(C16, B6, R1-1)、(C16, B6, R1-2)、(C16, B6, R1-3)、(C16, B7, R1-1)、(C16, B7, R1-2)、(C16, B7, R1-3)、(C16, B8, R1-1)、(C16, B8, R1-2)、(C16, B8, R1-3)、(C16, B9, R1-1)、(C16, B9, R1-2)、(C16, B9, R1-3)、(C16, B10, R1-1)、(C16, B10, R1-2)、(C16, B10, R1-3)、(C17, B1, R1-1)、(C17, B1, R1-2)、(C17, B1, R1-3)、(C17, B2, R1-1)、(C17, B2, R1-2)、(C17, B2, R1-3)、(C17, B3, R1-1)、(C17, B3, R1-2)、(C17, B3, R1-3)、(C17, B4, R1-1)、(C17, B4, R1-2)、(C17, B4, R1-3)、(C17, B5, R1-1)、(C17, B5, R1-2)、(C17, B5, R1-3)、(C17, B6, R1-1)、(C17, B6, R1-2)、(C17, B6, R1-3)、(C17, B7, R1-1)、(C17, B7, R1-2)、(C17, B7, R1-3)、(C17, B8, R1-1)、(C17, B8, R1-2)、(C17, B8, R1-3)、(C17, B9, R1-1)、(C17, B9, R1-2)、(C17, B9, R1-3)、(C17, B10, R1-1)、(C17, B10, R1-2)、(C17, B10, R1-3)。 Furthermore, as a compound of the present invention, a compound having a group to be combined with the following formulas (C1) to (C17), the above (B1) to (B10), and the above (R1-1) to (R1-3) can be synthesized is there.

(C, B, R1) = (C1, B1, R1-1), (C1, B1, R1-2), (C1, B1, R1-3), (C1, B2, R1-1), (C1) , B2, R1-2), (C1, B2, R1-3), (C1, B3, R1-1), (C1, B3, R1-2), (C1, B3, R1-3), (C1 , B4, R1-1), (C1, B4, R1-2), (C1, B4, R1-3), (C1, B5, R1-1), (C1, B5, R1-2), (C1 , B5, R1-3), (C1, B6, R1-1), (C1, B6, R1-2), (C1, B6, R1-3), (C1, B7, R1-1), (C1 , B7, R1-2), (C1, B7, R1-3), (C1, B8, R1-1), (C1, B8, R1-2), (C1, B8, R1-3), (C1 , B9, R1-1), (C1, B9, R1-2), (C1, B9, R1-3), (C1, B10, R1-1), (C1, B10, R1-2), (C1 , B10, R1-3), (C2, B1, R1-1), (C2, B1, R1-2), (C2, B1, R1-3), (C2, B2, R1-1), (C2 , B2, R1-2), (C2, B2, R1-3), (C2, B3, R1-1), (C2, B3, R1-2), (C2, B3, R1-3), (C2 , B4, R1-1), (C2, B4, R1-2), (C2, B4, R1-3), (C2, B5, R1-1), (C2, B5, R1-2), (C2 , B5, R1-3), (C2, B6, R1-1), (C2, B6, R1-2), (C2, B6, R1-3), (C2, B7, R1-1), (C2 , B7, R1-2), (C2, B7, R1-3), (C2, B8, R1-1), (C2, B8, R1-2), (C2, B8, R1-3), (C2 , B9, R1-1), (C2, B9, R1-2), (C2, B9, R1-3), (C2, B10, R1-1) , (C2, B10, R1-2), (C2, B10, R1-3), (C3, B1, R1-1), (C3, B1, R1-2), (C3, B1, R1-3) , (C3, B2, R1-1), (C3, B2, R1-2), (C3, B2, R1-3), (C3, B3, R1-1), (C3, B3, R1-2) , (C3, B3, R1-3), (C3, B4, R1-1), (C3, B4, R1-2), (C3, B4, R1-3), (C3, B5, R1-1) (C3, B5, R1-2), (C3, B5, R1-3), (C3, B6, R1-1), (C3, B6, R1-2), (C3, B6, R1-3) (C3, B7, R1-1), (C3, B7, R1-2), (C3, B7, R1-3), (C3, B8, R1-1), (C3, B8, R1-2) (C3, B8, R1-3), (C3, B9, R1-1), (C3, B9, R1-2), (C3, B9, R1-3), (C3, B10, R1-1) , (C3, B10, R1-2), (C3, B10, R1-3), (C4, B1, R1-1), (C4, B1, R1-2), (C4, B1, R1-3) , (C4, B2, R1-1), (C4, B2, R1-2), (C4, B2, R1-3), (C4, B3, R1-1), (C4, B3, R1-2) , (C4, B3, R1-3), (C4, B4, R1-1), (C4, B4, R1-2), (C4, B4, R1-3), (C4, B5, R1-1) , (C4, B5, R1-2), (C4, B5, R1-3), (C4, B6, R1-1), (C4, B6, R1-2), (C4, B6, R1-3) , (C4, B7, R1-1), (C4, B7, R1-2), (C4, B7, R1-3), (C4, B8, R1-1), (C4, B8, R1-2) , (C4, B8, R1-3), (C4, B9, R1-1), (C4, B9, R1-2), (C4, B) 9, R1-3), (C4, B10, R1-1), (C4, B10, R1-2), (C4, B10, R1-3), (C5, B1, R1-1), (C5, B1) B1, R1-2), (C5, B1, R1-3), (C5, B2, R1-1), (C5, B2, R1-2), (C5, B2, R1-3), (C5, B2) B3, R1-1), (C5, B3, R1-2), (C5, B3, R1-3), (C5, B4, R1-1), (C5, B4, R1-2), (C5, B) B4, R1-3), (C5, B5, R1-1), (C5, B5, R1-2), (C5, B5, R1-3), (C5, B6, R1-1), (C5, B) B6, R1-2), (C5, B6, R1-3), (C5, B7, R1-1), (C5, B7, R1-2), (C5, B7, R1-3), (C5, B) B8, R1-1), (C5, B8, R1-2), (C5, B8, R1-3), (C5, B9, R1-1), (C5, B9, R1-2), (C5, B) B9, R1-3), (C5, B10, R1-1), (C5, B10, R1-2), (C5, B10, R1-3), (C6, B1, R1-1), (C6, B1, R1-2), (C6, B1, R1-3), (C6, B2, R1-1), (C6, B2, R1-2), (C6, B2, R1-3), (C6, B2) B3, R1-1), (C6, B3, R1-2), (C6, B3, R1-3), (C6, B4, R1-1), (C6, B4, R1-2), (C6, B) B4, R1-3), (C6, B5, R1-1), (C6, B5, R1-2), (C6, B5, R1-3), (C6, B6, R1-1), (C6, B6, R1-2), (C6, B6, R1-3), (C6, B7, R1-1), (C6, B7, R1-2), (C6, B7, R1-3), (C6, B) B8, R1-1), (C6, B8, R1-2), (C6, B8, R1-3), (C6, B9, R1-1) , (C6, B9, R1-2), (C6, B9, R1-3), (C6, B10, R1-1), (C6, B10, R1-2), (C6, B10, R1-3) , (C7, B1, R1-1), (C7, B1, R1-2), (C7, B1, R1-3), (C7, B2, R1-1), (C7, B2, R1-2) , (C7, B2, R1-3), (C7, B3, R1-1), (C7, B3, R1-2), (C7, B3, R1-3), (C7, B4, R1-1) , (C7, B4, R1-2), (C7, B4, R1-3), (C7, B5, R1-1), (C7, B5, R1-2), (C7, B5, R1-3) (C7, B6, R1-1), (C7, B6, R1-2), (C7, B6, R1-3), (C7, B7, R1-1), (C7, B7, R1-2) (C7, B7, R1-3), (C7, B8, R1-1), (C7, B8, R1-2), (C7, B8, R1-3), (C7, B9, R1-1) (C7, B9, R1-2), (C7, B9, R1-3), (C7, B10, R1-1), (C7, B10, R1-2), (C7, B10, R1-3) , (C8, B1, R1-1), (C8, B1, R1-2), (C8, B1, R1-3), (C8, B2, R1-1), (C8, B2, R1-2) , (C8, B2, R1-3), (C8, B3, R1-1), (C8, B3, R1-2), (C8, B3, R1-3), (C8, B4, R1-1) , (C8, B4, R1-2), (C8, B4, R1-3), (C8, B5, R1-1), (C8, B5, R1-2), (C8, B5, R1-3) (C8, B6, R1-1), (C8, B6, R1-2), (C8, B6, R1-3), (C8, B7, R1-1), (C8, B7, R1-2) , (C8, B7, R1-3), (C8, B8, R1-1), (C8, B8, R1-2), (C8, B8, R1-3), (C8, B9, R1-1), (C8, B9, R1-2), (C8, B9, R1-3), (C8, B10, R1-1), (C8, B) B10, R1-2), (C8, B10, R1-3), (C9, B1, R1-1), (C9, B1, R1-2), (C9, B1, R1-3), (C9, B1) B2, R1-1), (C9, B2, R1-2), (C9, B2, R1-3), (C9, B3, R1-1), (C9, B3, R1-2), (C9, B) B3, R1-3), (C9, B4, R1-1), (C9, B4, R1-2), (C9, B4, R1-3), (C9, B5, R1-1), (C9, B) B5, R1-2), (C9, B5, R1-3), (C9, B6, R1-1), (C9, B6, R1-2), (C9, B6, R1-3), (C9, B) B7, R1-1), (C9, B7, R1-2), (C9, B7, R1-3), (C9, B8, R1-1), (C9, B8, R1-2), (C9, B) B8, R1-3), (C9, B9, R1-1), (C9, B9, R1-2), (C9, B9, R1-3), (C9, B10, R1-1), (C9, B) B10, R1-2), (C9, B10, R1-3), (C10, B1, R1-1), (C10, B1, R1-2), (C10, B1, R1-3), (C10, B1) B2, R1-1), (C10, B2, R1-2), (C10, B2, R1-3), (C10, B3, R1-1), (C10, B3, R1-2), (C10, B) B3, R1-3), (C10, B4, R1-1), (C10, B4, R1-2), (C10, B4, R1-3), (C10, B5, R1-1), (C10, B5, R1-2), (C10, B5, R1-3), (C10, B6, R1-1), (C10, B6, R1-2), (C10, B6, R1-3), (C10, B7, R1-1), (C10, B7, R1-2), (C10, B7, R1-3), (C10, B8, R1-1), (C10, B8, R1-2), (C10, B8, R1-3), (C10, B9, R1-1), (C10, B9, R1-2), (C10, B9, R1-3), (C10, B10, R1-1), (C10, B10, R1-2), (C10, B10, R1-3), (C11, B1, B1) R1-1), (C11, B1, R1-2), (C11, B1, R1-3), (C11, B2, R1-1), (C11, B2, R1-2), (C11, B2, R12) R1-3), (C11, B3, R1-1), (C11, B3, R1-2), (C11, B3, R1-3), (C11, B4, R1-1), (C11, B4, R1-2), (C11, B4, R1-3), (C11, B5, R1-1), (C11, B5, R1-2), (C11, B5, R1-3), (C11, B6, R1-1), (C11, B6, R1-2), (C11, B6, R1-3), (C11, B7, R1-1), (C11, B7, R1-2), (C11, B7, R1-3), (C11, B8, R1-1), (C11, B8, R1-2), (C11, B8, R1-3), (C11, B9, R1-1), (C11, B9, R1-2), (C11, B9, R1-3), (C11, B10, R1-1), (C11, B10, R1-2), (C11, B10, R1-3), (C12, B1, R1) R1-1), (C12, B1, R1-2), (C12, B1, R1-3), (C12, B2, R1-1), (C12, B2, R1-2), (C12, B2, R12) R1-3), (C12, B3, R1-1), (C12, B3, R1-2), (C12, B3, R1-3), (C12, B4, R1-1), (C12, B4, R12) R1-2), (C12, B4, R1-3), (C12, B5, R1-1), (C12, B5, R1-2), (C12, B5, R1-3), (C12, B6, R1-1 ), (C12, B6, R1-2), (C12, B6, R1-3), (C12, B7, R1-1), (C12, B7, R1-2), (C12, B7, R1-3) ), (C12, B8, R1-1), (C12, B8, R1-2), (C12, B8, R1-3), (C12, B9, R1-1), (C12, B9, R1-2) ), (C12, B9, R1-3), (C12, B10, R1-1), (C12, B10, R1-2), (C12, B10, R1-3), (C13, B1, R1-1) ), (C13, B1, R1-2), (C13, B1, R1-3), (C13, B2, R1-1), (C13, B2, R1-2), (C13, B2, R1-3) ), (C13, B3, R1-1), (C13, B3, R1-2), (C13, B3, R1-3), (C13, B4, R1-1), (C13, B4, R1-2) ), (C13, B4, R1-3), (C13, B5, R1-1), (C13, B5, R1-2), (C13, B5, R1-3), (C13, B6, R1-1) ), (C13, B6, R1-2), (C13, B6, R1-3), (C13, B7, R1-1), (C13, B7, R1-2), (C13, B7, R1-3) ), (C13, B8, R1-1), (C13, B8, R1-2), (C13, B8, R1-3), (C13, B9, R1-1), (C13, B9, R1-2) ), (C13, B9, R1-3), (C13, B10, R1-1), (C13, B10, R1-2), (C13, B10, R1-3), (C14, B1, R1-1) ), (C14, B1, R1-2), (C14, B1, R1-3), (C14, B2, R1-1), (C14, B2, R1-2), (C14, B2, R1-3) ), (C14, B3, R1-1), (C14, B3, R1-2), (C14, B3, R1-3), (C14, B4, R1-1), (C14, B4, R1-2) ), (C14, B4, R1-3), (C14, B5, R1-1), (C14, B5, R1-2), (C14, B5, R1-3), (C14, B6, R1-1), (C14, B6, R1-2), (C14, B6, R1-3), (C14, B7, R1-1), (C14, B7, R1-2), (C14, B7, R1-3), (C14, B8, R1-1), (C14, B8, R1-2), (C14, B8, R1-3), (C14, B9, R1-1), (C14, B9, R1-2), (C14, B9, R1-3), (C14, B10, R1-1), (C14, B10, R1-2), (C14, B10, R1-3), (C15, B1, R1-1), (C15, B1, R1-2), (C15, B1, R1-3), (C15, B2, R1-1), (C15, B2, R1-2), (C15, B2, R1-3), (C15, B3, R1-1), (C15, B3, R1-2), (C15, B3, R1-3), (C15, B4, R1-1), (C15, B4, R1-2), (C15, B4, R1-3), (C15, B5, R1-1), (C15, B5, R1-2), (C15, B5, R1-3), (C15, B6, R1-1), (C15, B6, R1-2), (C15, B6, R1-3), (C15, B7, R1-1), (C15, B7, R1-2), (C15, B7, R1-3), (C15, B8, R1-1), (C15, B8, R1-2), (C15, B8, R1-3), (C15, B9, R1-1), (C15, B9, R1-2), (C15, B9, R1-3), (C15, B10, R1-1), (C15, B10, R1-2), (C15, B10, R1-3), (C16, B1, R1-1), (C16, B1, R1-2), (C16, B1, R1-3), (C16, B2, R1-1), (C16, B2, R1-2), (C16, B2, R1-3), (C16 , B3, R1-1), (C16, B3, R1-2), (C16, B3, R1-3), (C16, B4, R1-1), (C16, B4, R1-2), (C16) , B4, R1-3), (C16, B5, R1-1), (C16, B5, R1-2), (C16, B5, R1-3), (C16, B6, R1-1), (C16) , B6, R1-2), (C16, B6, R1-3), (C16, B7, R1-1), (C16, B7, R1-2), (C16, B7, R1-3), (C16) , B8, R1-1), (C16, B8, R1-2), (C16, B8, R1-3), (C16, B9, R1-1), (C16, B9, R1-2), (C16) , B9, R1-3), (C16, B10, R1-1), (C16, B10, R1-2), (C16, B10, R1-3), (C17, B1, R1-1), (C17) , B1, R1-2), (C17, B1, R1-3), (C17, B2, R1-1), (C17, B2, R1-2), (C17, B2, R1-3), (C17) , B3, R1-1), (C17, B3, R1-2), (C17, B3, R1-3), (C17, B4, R1-1), (C17, B4, R1-2), (C17) , B4, R1-3), (C17, B5, R1-1), (C17, B5, R1-2), (C17, B5, R1-3), (C17, B6, R1-1), (C17) , B6, R1-2), (C17, B6, R1-3), (C17, B7, R1-1), (C17, B7, R1-2), (C17, B7, R1-3), (C17) , B8, R1-1), (C17, B8, R1-2), (C17, B8, R1-3), (C17, B9, R1-1), (C17, B9, R1-2), (C17) , B9, R1-3), (C17, B10, R1-1), (C17, B10, R1-2), (C17, B10, R1-3).

  Below, the biological test example of this invention compound is described.

Test Example 1: Measurement of cap-dependent endonuclease (CEN) inhibitory activity 1) Preparation of substrate
A 30-mer RNA (5'-pp- [5] in which G at the 5 'end is modified by 2 phosphorylation, and the hydroxyl group at the 2' position is methoxylated and modified, and the 6th U from the 5 'end is Cy3 labeled and BHQ2 labeled at the 3' end. m2'-O] GAA UAU (-Cy3) GCA UCA CUA GUA AGC UUU GCU CUA-BHQ2-3 '(manufactured by Japan Bioservices Co., Ltd.) is purchased and cap structure is generated using a script cap (ScriptCap) system manufactured by EPICENTRE. (Product is m7G [5 ']-ppp- [5'] [m2'-O] GAA UAU (-Cy3) GCA UCA CUA GUA AGC UUU GCU CUA (-BHQ2) -3 '). This was separated and purified by denaturing polyacrylamide gel electrophoresis and used as a substrate.
2) Preparation of enzyme
RNP was prepared from virus particles according to a standard method (Reference: VIROLOGY (1976) 73, p327-338 OLGA M. ROCHOVANSKY). Specifically, 200 μL of A / WSN / 33 virus 1 × 10 ³ PFU / mL was inoculated into 10-day-old embryonated chicken eggs and cultured at 37 ° C. for 2 days, and then the urine of the eggs was collected. The virus particles are purified by ultracentrifugation using 20% sucrose, and after solubilizing the virus particles using Triton X-100 and lysolecithin, the RNP fraction (50 by ultracentrifugation using a 30-70% glycerol density gradient) The 70% glycerol fraction) was collected and used as an enzyme solution (containing about 1 nM PB1.PB2.PA complex).
3) Enzyme reaction Enzyme reaction solution (Composition: 53 mM Tris-hydrochloride (pH 7.8), 1 mM MgCl ₂ , 1.25 mM dithiothreitol, 80 mM NaCl, 12.5% glycerol, enzyme solution 0.15 μL in a 384-well plate made of polypropylene Was dispensed in 2.5 μL. Next, 0.5 μL of DMSO was added to 0.5 μL of the test compound solution serially diluted in dimethyl sulfoxide (DMSO), the positive control (PC) and the negative control (NC), and mixed well. Next, 2 μL of substrate solution (1.4 nM substrate RNA, 0.05% Tween 20) is added to start the reaction, and after incubating for 60 minutes at room temperature, 1 μL of the reaction solution is dissolved in 10 μL of Hi-Di Formamide solution (GeneScan 120 Liz Size as a sizing marker) Standard included: Applied Biosystems (ABI)) to stop the reaction. NC was previously stopped by adding EDTA (4.5 mM) before starting the reaction (all indicated concentrations are final concentrations).
3) Measurement of inhibition rate (IC ₅₀ value) The quenched solution was heated at 85 ° C. for 5 minutes, quenched on ice for 2 minutes, and analyzed by ABI PRIZM 3730 Genetic Analyzer. The peak of cap-dependent endonuclease product is quantified by analysis software ABI Genemapper, and after determining the CEN reaction inhibition rate (%) of the test compound as 0% inhibition and 100% inhibition, respectively, the fluorescence intensity of PC and NC is a curve IC ₅₀ values were determined using a fitting software (such as XLfit 2.0: Model 205 (IDBS)).

Test example 2: CPE suppression effect confirmation test <material>
2% FCS E-MEM (adjusted by adding kanamycin and FCS to MEM (Minimum Essential Medium) (Invitrogen))
0.5% BSA E-MEM (adjusted by adding kanamycin and BSA to MEM (Minimum Essential Medium) (Invitrogen))
-HBSS (hanks' Balanced Salt Solution)
・ MDBK cells
The appropriate cell number (3 × 10 ⁵ / mL) was adjusted with 2% FCS E-MEM.
・ MDCK cells
After washing twice with HBSS, the number of cells (5 × 10 ⁵ / mL) was adjusted to an appropriate number with 0.5% BSA E-MEM.
Trypsin solution
Trypsin from porcine pancreas (SIGMA) was dissolved in PBS (-), and filtered with a 0.45 um filter.
EnVision (PerkinElmer)
・ WST-8 Kit (Kishida Chemical)
・ 10% SDS solution

<Operation procedure>
-Dilution of test sample: 2% FCS E-MEM was used when MDBK cells were used, and 0.5% BSA E-MEM was used when MDCK cells were used as culture medium. Hereinafter, the same culture solution was used for dilution of virus, cells and test sample.
The test sample was previously diluted with culture solution to an appropriate concentration, and a 2- to 5-fold serial dilution series was prepared in a 96-well plate (50 μL / well). Two sheets were prepared for measuring anti-Flu activity and for measuring cytotoxicity. A triple determination was performed for each drug.
When MDCK cells were used, Trypsin was added to cells to a final concentration of 3 ug / mL only for anti-Flu activity measurement.
Influenza virus dilution and dispensing In advance, the influenza virus was diluted with culture medium to an appropriate concentration, and aliquoted at 50 μL / well to a 96-well plate containing a test sample. The culture solution was dispensed at 50 μl / well to a plate for cytotoxicity measurement.
-Dilution of cells, dispensing The cells adjusted to the appropriate number of cells were dispensed in 100 μL / well to a 96-well plate containing a test sample.
Mix with plate mixer and incubate in a CO ₂ incubator. Both for the measurement of anti-Flu activity and for the measurement of cytotoxicity were cultured for 3 days.
・ WST-8 dispensing
The 96-well plate cultured for 3 days was observed with a naked eye and under a microscope to confirm cell morphology, presence or absence of crystals, and the like. The supernatant was removed so as not to absorb cells from the plate.
The WST-8 Kit was diluted 10-fold in culture medium, and 100 μL of this WST-8 solution was dispensed to each well. After mixing with a plate mixer, the cells were cultured in a CO ₂ incubator for 1 to 3 hours.
For the plate for measurement of anti-Flu activity, after culture, 10 uL of 10% SDS solution was dispensed to each well to inactivate the virus.
Measurement of Absorbance The absorbance of the mixed 96-well plate was measured at EnVision at two wavelengths of 450 nm / 620 nm.

<Calculation of each measurement item value>
Calculation was performed using Microsoft Excel or a program having equivalent computational processing power based on the following formula.
・ 50% influenza infection cell death inhibition concentration (EC ₅₀ ) calculation
EC ₅₀ = 10 ^Z
Z = (50%-High%) / (High%-Low%) x {log (High conc.)-Log (Low conc.)} + Log (High conc.)
The measurement results are shown below.
Compound I-1: EC50 = 18.2 nM
Compound I-2: EC50 = 207 nM
Compound I-3: EC50 = 283 nM

Test Example 3: CYP Inhibition Test O-deethylation of 7-ethoxyresorufin as a typical substrate metabolic reaction of human major CYP5 species (CYP1A2, 2C9, 2C19, 2D6, 3A4) using commercially available pooled human liver microsomes (CYP1A2), methyl-hydroxylation of tolbutamide (CYP2C9), 4'-hydroxylation of mephenytoin (CYP2C19), O-demethylation of dextromethorphan (CYP2D6), hydroxylation of terfenadine (CYP3A4) as indices The extent to which the amount of metabolite production of is inhibited by the compound of the present invention is evaluated.

  The reaction conditions are as follows: substrate, 0.5 μmol / L ethoxyresorufin (CYP1A2), 100 μmol / L tolbutamide (CYP2C9), 50 μmol / L S-mephenytoin (CYP2C19), 5 μmol / L dextromethorphan (CYP2D6), Reaction time, 15 minutes; reaction temperature, 37 ° C .; enzyme, pooled human liver microsome 0.2 mg protein / mL; compound concentration of the present invention: 1, 5, 10, 20 μmol / L (4 points) .

  Add 5 substrates, human liver microsome, and the compound of the present invention to the reaction solution as a reaction solution in a 96-well plate in 50 mmol / L Hepes buffer, add NADPH which is a coenzyme, and use it as an indicator for metabolic reaction To start. After reacting for 15 minutes at 37 ° C., the reaction is stopped by adding a solution of methanol / acetonitrile = 1/1 (V / V). After centrifugation at 3000 rpm for 15 minutes, resorufin (CYP1A2 metabolite) in the centrifugation supernatant is quantified with a fluorescent multilabel counter, tolbutamide hydroxylate (CYP2C9 metabolite), mephenytoin 4 'hydroxylate (CYP2C19 metabolite) , Dextrorphan (CYP2D6 metabolite), terfenadine alcohol (CYP3A4 metabolite) is quantified by LC / MS / MS.

A control (100%) was obtained by adding only DMSO, which is a solvent in which the compound of the present invention was dissolved, as a control (100%), and the residual activity (%) at each concentration of the compound of the present invention added to the solvent was calculated. The IC ₅₀ is calculated by inverse estimation with a logistic model using

Test Example 4: BA test Examination of oral absorbability Experimental material and method (1) Animal used: Mouse or SD rat is used.
(2) Breeding conditions: Mice or SD rats have free access to chow and sterile tap water.
(3) Dosage, setting of grouping: oral administration, intravenous administration by a predetermined dose. Set groups as follows: (The dose has been changed for each compound)
Oral administration 1 to 30 mg / kg (n = 2 to 3)
Intravenous administration 0.5 to 10 mg / kg (n = 2 to 3)
(4) Preparation of administration solution: Oral administration is administered as a solution or a suspension. Intravenous administration is solubilized and administered.
(5) Administration method: Oral administration is orally administered orally by oral sound. Intravenous administration is performed from the tail vein by a syringe with a needle.
(6) Evaluation items: Blood is collected over time, and the concentration of the compound of the present invention in plasma is measured using LC / MS / MS.
(7) Statistical analysis: With respect to the change in concentration of the compound of the present invention in plasma, the area under the plasma concentration-time curve (AUC) is calculated using the non-linear least squares method program WinNonlin®, and oral administration group and intravenous administration The bioavailability (BA) of the compound of the present invention is calculated from the AUC of the group.

Test Example 5: Metabolic Stability Test A commercially available pooled human liver microsome and the compound of the present invention are reacted for a certain period of time, the remaining rate is calculated by comparing the reaction sample and the unreacted sample, and the degree of metabolism of the compound of the present invention in the liver is evaluated. Do.

  Human liver microsome 0.5 mg protein / mL in 0.2 mL of buffer (50 mmol / L Tris-HCl pH 7.4, 150 mmol / L potassium chloride, 10 mmol / L magnesium chloride) in the presence of 1 mmol / L NADPH Incubate at 37 ° C for 0 or 30 minutes (oxidative reaction). After the reaction, 50 μL of the reaction solution is added to 100 μL of a methanol / acetonitrile = 1/1 (v / v) solution, mixed, and centrifuged at 3000 rpm for 15 minutes. The compound of the present invention in the supernatant of the centrifugation is quantified by LC / MS / MS, and the remaining amount of the compound of the present invention after reaction is calculated with the amount of compound at the time of 0 minutes reaction as 100%. The hydrolysis reaction is carried out in the absence of NADPH, and the glucuronidation reaction is carried out in the presence of 5 mmol / L UDP-glucuronic acid instead of NADPH, and the same operation is carried out thereafter.

Test Example 6: CYP3A4 Fluorescent MBI Test The CYP3A4 fluorescent MBI test is a test to examine the enhancement of CYP3A4 inhibition of the compound of the present invention by metabolic reaction. The 7-benzyloxytrifluoromethylcoumarin (7-BFC) is debenzylated by the CYP3A4 enzyme (E. coli expression enzyme) to yield the fluorescent metabolite 7-hydroxytrifluoromethylcoumarin (7-HFC). CYP3A4 inhibition is evaluated using 7-HFC generation reaction as an index.

  The reaction conditions are as follows: substrate, 5.6 μmol / L 7-BFC; pre-reaction time, 0 or 30 minutes; reaction time, 15 minutes; reaction temperature, 25 ° C. (room temperature); CYP3A4 content (E. coli expression enzyme), 62.5 pmol / mL at the time of pre-reaction, 6.25 pmol / mL at the time of reaction (during 10-fold dilution); Compound concentration of the present invention, 0.625, 1.25, 2.5, 5, 10, 20 μmol / L (6 points ).

  The enzyme and the compound of the present invention are added to a 96-well plate as a pre-reaction solution in K-Pi buffer (pH 7.4) with the composition of the above pre-reaction, and another 96-well plate with substrate and K-Pi buffer Transfer a portion of it to be diluted 1/10, add the coenzyme NADPH, start the reaction as an indicator (pre-reaction absent), and after reaction for a predetermined time, acetonitrile / 0.5 mol / L The reaction is quenched by the addition of Tris (trishydroxyaminomethane) = 4/1 (V / V). In addition, NADPH is also added to the remaining pre-reaction solution to start pre-reaction (pre-reaction included), and after a predetermined time of pre-reaction, another plate is diluted 1/10 with the substrate and K-Pi buffer. Shift the part and start the reaction as index. After reaction for a predetermined time, the reaction is stopped by adding acetonitrile / 0.5 mol / L Tris (trishydroxyaminomethane) = 4/1 (V / V). The fluorescence value of 7-HFC which is a metabolite is measured with the fluorescence plate reader for the plate which performed each index reaction. (Ex = 420 nm, Em = 535 nm)

A control (100%) was obtained by adding only DMSO, which is a solvent in which the compound of the present invention was dissolved, to the reaction system, and the residual activity (%) when each concentration of the compound of the present invention was added was calculated. The IC ₅₀ is calculated by inverse estimation with a logistic model using The case where the difference between IC ₅₀ values is 5 μmol / L or more is (+), and the case where the difference is 3 μmol / L or less is (−).

Test Example 7: Fluctuation Ames Test
The mutagenicity of the compounds of the present invention is evaluated.
20 μL of cryopreservation S. typhimurium (Salmonella typhimurium strain TA98 strain, strain TA100) is inoculated into 10 mL liquid nutrient medium (2.5% Oxoid nutrient broth No. 2) and shake precultured at 37 ° C. for 10 hours. The TA98 strain is centrifuged (2000 × g, 10 minutes) to remove the culture solution by centrifugation of 9 mL of the bacterial solution. 9 mL of 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: 0. Suspend the bacteria in 25 g / L, MgSO ₄ · 7 H ₂ 0: 0.1 g / L, and use 110 mL of Exposure medium (Biotin: 8 μg / mL, histidine: 0.2 μg / mL, glucose: 8 mg / mL) Buffer). The TA100 strain is added to 120 mL of Exposure medium with respect to 3.16 mL bacterial solution to prepare a test bacterial solution. The compound of the present invention DMSO solution (maximum dose 50 mg / mL to several dilutions by 2-3 times common ratio), DMSO as a negative control, 50 μg / mL 4- Nitroquinoline 1-oxide DMSO solution, 0.25 μg / mL 2- (2-furyl) -3- (5-nitro-2-furyl) acrylamide DMSO solution for strain TA100, TA98 for metabolic activation conditions 12 μL each of 40 μg / mL 2-aminoanthracene DMSO solution for the strain and 20 μg / mL 2-aminoanthracene DMSO solution for the TA 100 strain (588 μL of the test solution under metabolic activation conditions and 498 μL of the test solution) Mix 90 μL of the mixture) and shake culture at 37 ° C. for 90 minutes. Indicator medium (MicroF buffer solution containing biotin: 8 μg / mL, histidine: 0.2 μg / mL, glucose: 8 mg / mL, bromocresol purple: 37.5 μg / mL), and 460 μL of the bacterial solution to which the compound of the present invention was exposed And aliquot 50 μL each into 48 wells / dose of microplate, and incubate at 37 ° C. for 3 days. The wells containing bacteria that have acquired growth ability by mutation of amino acid (histidine) synthetase gene turn from purple to yellow due to pH change, therefore count the bacteria growth wells in 48 wells per dose. , Evaluated in comparison with the negative control group. Those with negative mutagenicity are shown as (-), and those with positive are shown as (+).

Test Example 8 hERG test In order to evaluate the electrocardiogram QT interval prolongation risk of the compound of the present invention, it is important for the ventricular repolarization process using HEK 293 cells in which human ether-a-go-go related gene (hERG) channel is expressed. The effects of the compounds of the present invention on delayed rectifier K ⁺ current (I _Kr ), which plays a
After holding the cells at -80 mV membrane potential by whole cell patch clamp method using a fully automatic patch clamp system (PatchXpress 7000A, Axon Instruments Inc.), +40 mV depolarization stimulation for 2 seconds, further -50 mV repolarization Record the induced I _Kr when the stimulus is given for 2 seconds. After the generated current is stabilized, an extracellular solution (NaCl: 135 mmol / L, KCl: 5.4 mmol / L, NaH ₂ PO ₄ : 0.3 mmol / L) in which the compound of the present invention is dissolved at a target concentration _{CaCl 2 · 2H 2 O: 1.8mmol} / L, MgCl 2 · 6H 2 O: 1mmol / L, glucose: 10mmol / L, HEPES (4- (2- hydroxyethyl) -1-piperazine-ethanesulfonic acid): 10 mmol / L, pH = 7.4) is applied to the cells for 10 minutes at room temperature. From the obtained I _Kr , using the analysis software (DataXpress ver. 1, Molecular Devices Corporation), the absolute value of the maximum tail current is measured based on the current value at the holding membrane potential. Furthermore, the inhibition rate for the maximum tail current before application of the compound of the present invention is calculated, and the effect of the compound of the present invention on I _Kr is evaluated in comparison with the vehicle application group (0.1% dimethyl sulfoxide solution).

Test Example 9 Solubility Test The solubility of the compound of the present invention was determined under 1% DMSO addition conditions. Prepare a 10 mmol / L compound solution with DMSO, and add 2 μL of the compound solution of the present invention as JP-1 solution (adding water to 2.0 g of sodium chloride and 7.0 mL of hydrochloric acid to make 1000 mL), JP-2 solution (phosphorus) 3.40 g of potassium dihydrogen and 3.55 g of anhydrous disodium hydrogen phosphate dissolved in water and added to 1 volume of water to 1 volume of 1000 mL add 1 volume of water). After shaking for 1 hour at room temperature, the mixture is filtered. Each filtrate is diluted 10-fold with methanol / water = 1/1 (V / V), and the concentration in the filtrate is measured using LC / MS by an absolute calibration method.

Test Example 10 Powder Solubility Test An appropriate amount of the compound of the present invention was placed in a suitable container, and each container was filled with JP-1 solution (sodium chloride 2.0 g, 7.0 mL hydrochloric acid with water to make 1000 mL), JP-2 solution (500 mL of water was added to 500 mL of pH 6.8 phosphate buffer) 200 μL of 20 mmol / L sodium taurocholate (TCA) / JP-2 solution (JPA solution is added to 1.08 g of TCA to make 100 mL) Add one by one. When the entire solution is dissolved after addition of the test solution, the compound of the present invention is appropriately added. The mixture is sealed, shaken at 37 ° C. for 1 hour and filtered, and 100 μL of methanol is added to 100 μL of each filtrate to perform 2-fold dilution. The dilution factor is changed as needed. Make sure that there are no bubbles and precipitates, shake tightly and tightly. The compound of the present invention is quantified using HPLC by an absolute calibration method.

Test Example 11 Ames test Using Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA as test strains, the Ames test was performed under non-metabolic activation and metabolic activation conditions by the preincubation method. The method is carried out to examine the presence or absence of gene mutagenicity of the compound according to the present invention.

Test Example 12 Light Hemolysis Test The compound of the present invention is dissolved at a target concentration, and a red blood cell suspension (2.5 v / v%) at a concentration of 0.1 to 0.0008% prepared on sheep's defibrated blood And UV irradiation (10 J / cm ² , 290-400 nm) in the UVA and UVB regions using an ultraviolet fluorescent lamp (GL20SE lamp, Sankyo Electric and FL20S-BLB lamp, Panasonic). Collect the mixed solution after the end of light irradiation and centrifuge. After the supernatant after centrifugation is collected and transferred to a microplate, the absorbance (540 or 630 nm) of the supernatant is measured, and determination based on the absorbance is performed. The absorbances at 540 and 630 nm are indicators of biomembrane damage (% light hemolysis rate) and lipid membrane peroxidation (methemoglobin production), respectively. When the light hemolysis rate is less than 10% and the change in absorbance at 630 nm is less than 0.05, (-) is given, the light hemolysis rate is 10% or more, and the change in absorbance at 630 nm is 0. The case of 05 or more is (+).

Formulation Examples The following formulation examples are merely illustrative and are not intended to limit the scope of the invention in any way.
Formulation Example 1: Tablet The compound of the present invention, lactose and calcium stearate are mixed, crushed and granulated, and dried to form granules of an appropriate size. Next, calcium stearate is added and compression molded into tablets.

Formulation Example 2: Capsule The compound of the present invention, lactose and calcium stearate are uniformly mixed to make a powder as a powder or fine particles. It is filled in a capsule container to make a capsule.

Formulation Example 3: Granules The compound of the present invention, lactose and calcium stearate are uniformly mixed, compressed and molded, and then crushed, sized and sieved to give granules of a suitable size.

Formulation Example 4: Orally disintegrating tablet The compound of the present invention and crystalline cellulose are mixed, granulated and then tableted to give an orally disintegrating tablet.

Formulation Example 5 Dry Syrup The compound of the present invention and lactose are mixed, crushed, sized and sieved to obtain a dry syrup of appropriate size.

Formulation Example 6: Injection The compound of the present invention and a phosphate buffer are mixed to prepare an injection.

Formulation Example 7 Instillation The compound of the present invention and a phosphate buffer are mixed to obtain an instillation.

Formulation Example 8: Inhalant The compound of the present invention and lactose are mixed and finely pulverized to give an inhalant.

Formulation Example 9 Ointment The compound of the present invention and petrolatum are mixed to obtain an ointment.

Formulation Example 10 Patch The compound of the present invention and a base such as an adhesive plaster are mixed to obtain a patch.

  The compounds according to the invention have cap-dependent endonuclease (CEN) inhibitory activity after absorption into the body. The compound according to the present invention can be a medicament useful as a therapeutic and / or preventive agent for symptoms and / or diseases induced by infection with influenza virus.

Claims (15)

Formula (I):

(In the formula,
P is hydrogen or a group forming a prodrug;
One of B ¹ and B ² is NR ² , and the other is CR ^3a R ^3b ;
R ¹ is hydrogen, halogen, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, substituted with substituent group C Optionally alkynyl, alkyloxy optionally substituted with substituent group C, alkenyloxy optionally substituted with substituent group C, alkylcarbonyl optionally substituted with substituent group C, substituent group Alkyloxycarbonyl which may be substituted by C, carbocyclic group which may be substituted by substituent group C, carbocyclic alkyl which may be substituted by substituent group C, substituted by substituent group C Optionally substituted carbocycle oxy, optionally substituted carbocycle oxycarbonyl, optionally substituted substituent C, optionally substituted heterocyclic alkyl, optionally substituted substituent C Heterocyclic oxy, heterocyclic oxycarbonyl optionally substituted with substituent group C,
-Z-N (R ^A1 ) (R ^A2 ),
_{^{-Z-N (R A3) -SO}} 2 - (R A4),
^{-Z-C (= O) -N} (R A5) -SO 2 - (R A6),
-Z-N ( ^RA7 ) -C (= O) ^-RA8 ,
-Z-S-R ^A9 ,
-Z-SO _2- R ^A10 ,
-Z-S (= O) ^-RA11 ,
-Z-N (R < ^A12 >)-C (= O) -O-R < ^A13 >,
-Z-N ( ^RA14 ) -C (= O) -N ( ^RA15 ) ( ^RA16 ),
-Z-C (= O) -N ( ^RA17 ) -C (= O) -N ( ^RA18 ) ( ^RA19 ),
-Z-N ( ^RA20 ) -C (= O) -C (= O) ^-RA21 ,
-Z-B (-OR ^A22 ) (-OR ^A23 ) or -Z-SO ₂ -N (R ^A24 ) (R ^A25 ),
(Here, R ^A1 , R ^A2 , R ^A3 , R ^A5 , R ^A7 , R ^A8 , R ^A9 , R ^A12 , R ^A13 , R ^A14 , R ^A15 , R ^A16 , R ^A17 , R ^A18 , R ^A19 , R ^{A19 A20} , R ^A21 , R ^A24 and R ^A25 are each independently hydrogen, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, substituent group C Embedded image optionally substituted alkynyl, substituted carbocyclic group optionally substituted by substituent group C, heterocyclic group optionally substituted by substituent group C, substituted by substituent group C It is selected from the substituent group consisting of optionally substituted carbocyclic alkyl, and heterocyclic alkyl optionally substituted by substituent group C,
R ^A4 , R ^A6 , R ^A10 and R ^A11 are each independently an alkyl which may be substituted with substituent group C, an alkenyl which may be substituted with substituent group C, and a substituent group C Alkynyl which may be substituted, carbocyclic group which may be substituted with substituent group C, heterocyclic group which may be substituted with substituent group C, which may be substituted with substituent group C It is selected from the substituent group consisting of carbocyclic alkyl and heterocyclic alkyl optionally substituted by substituent group C,
R ^A1 and R ^A2 , R ^A15 and R ^A16 , and R ^A18 and R ^A19 may ^combine with adjacent atoms to form a heterocyclic ring,
R ^A22 and R ^A23 each independently represent a hydrogen atom, an alkyl which may be substituted with substituent group C, or R ^A22 and R ^A23 together with the adjacent atom And may form a heterocyclic ring, and Z is a single bond or linear or branched alkylene);

R ² , R ^3a and R ^3b are each independently hydrogen, carboxy, cyano, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, substituent group C , An optionally substituted alkynyl, a substituted group C optionally substituted alkylcarbonyl, a substituted group C optionally substituted alkyloxycarbonyl, and a substituted group C optionally substituted carbon Cyclic group, carbocyclic ring alkyl which may be substituted by substituent group C, carbocyclic ring oxyalkyl which may be substituted by substituent group C, carbocyclic ring carbonyl which may be substituted by substituent group C, Carbocyclic oxycarbonyl optionally substituted with substituent group C, heterocyclic group optionally substituted with substituent group C, heterocyclic alkyl optionally substituted with substituent group C, substituent group C And heterocyclic oxyalkyl which may be substituted, heterocyclic carbonyl which may be substituted with substituent group C, heterocyclic oxycarbonyl which may be substituted with substituent group C,
-Y-S-R ^B1 ,
-Z-S (= O) -R B2,
-Z-SO _2- R ^B3 ,
-C (= O) -C (= O) -R B4,
-C (= O) -N (R ^B5 ) (R ^B6 ),
-Z-C ( ^RB7 ) ( ^RB8 ) ( ^RB9 ),
_-Z-CH 2 -R ^B10,
-Z-N ( ^RB11 ) -C (= O) -O- ^RB12 or -Z-N ( ^RB13 ) -C (= O) ^-RB14
(Wherein, R ^B1 , R ^B4 , R ^B5 , R ^B6 , R ^B9 , R ^B11 , R ^B12 , R ^B13 , and R ^B14 may be each independently substituted with hydrogen or substituent group C. Alkyl, alkenyl optionally substituted with substituent group C, alkynyl optionally substituted with substituent group C, carbocyclic group optionally substituted with substituent group C, substituted with substituent group C A substituent group selected from a heterocyclic group which may be substituted, a carbocyclic alkyl which may be substituted with a substituent group C, and a heterocyclic alkyl which may be substituted with a substituent group C,
R ^B2 and R ^B3 are each independently an alkyl which may be substituted with substituent group C, an alkenyl which may be substituted with substituent group C, an alkynyl which may be substituted with substituent group C A carbocyclic group which may be substituted with substituent group C, a heterocyclic group which may be substituted with substituent group C, a carbocyclic alkyl which may be substituted with substituent group C, and a substituent It is selected from the substituent group consisting of the heterocyclic alkyl which may be substituted by the group group C,
R ^B7 , R ^B8 and R ^B10 are each independently a carbocyclic group which may be substituted with substituent group C or a heterocyclic group which may be substituted with substituent group C,
R ^B5 and R ^B6 may form a heterocycle together with adjacent atoms,
Y is linear or branched alkylene, and Z is a single bond or linear or branched alkylene)

R ⁴ is hydrogen, halogen, hydroxy, carboxy, cyano, formyl, alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, substituted with substituent group C Optionally alkynyl, alkyloxy optionally substituted with substituent group C, alkenyloxy optionally substituted with substituent group C, alkylcarbonyl optionally substituted with substituent group C, substituent group Alkyloxycarbonyl which may be substituted by C, carbocyclic group which may be substituted by substituent group C, carbocyclic alkyl which may be substituted by substituent group C, substituted by substituent group C Optionally substituted carbocyclic oxyalkyl, optionally substituted carbocyclic ring carbonyl, optionally substituted carbocyclic ring oxy, optionally substituted substituent C Carbocyclic ring oxycarbonyl which may be substituted, heterocyclic group which may be substituted with substituent group C, heterocyclic alkyl which may be substituted with substituent group C, even if substituted with substituent group C Good heterocyclic oxyalkyl, heterocyclic carbonyl optionally substituted with substituent group C, heterocyclic oxy optionally substituted with substituent group C, heterocyclic oxy optionally substituted with substituent group C Carbonyl,
_{^{-Z-N (R C1) -SO}} 2 -R C2,
-Z-N (R < ^C3 >)-C (= O) -R < ^C4 >,
-Z-N (R < ^C5 >)-C (= O) -O-R < ^C6 >,
-Z-C (= O) -N (R ^C7 ) (R ^C8 ),
-Z-N (R ^<C9> ) (R ^<C10> ),
_-Z-SO ^{2 -R C11} or ^{-Z-N (R C12),} -O-C (= O) -R C13
(Where, R ^C1 , R ^C3 , R ^C4 , R ^C5 , R ^C6 , R ^C7 , R ^C8 , R ^C9 , R ^C10 , R ^C12 and R ^C13 are each independently hydrogen, substituent group C Alkyl which may be substituted, alkenyl which may be substituted with substituent group C, alkynyl which may be substituted with substituent group C, carbocyclic group which may be substituted with substituent group C A heterocyclic group optionally substituted with substituent group C, a carbocyclic alkyl optionally substituted with substituent group C, and a heterocyclic alkyl optionally substituted with substituent group C Selected from the group
R ^C2 and R ^C11 are each independently alkyl optionally substituted with substituent group C, alkenyl optionally substituted with substituent group C, and alkynyl optionally substituted with substituent group C A carbocyclic group which may be substituted with substituent group C, a heterocyclic group which may be substituted with substituent group C, a carbocyclic alkyl which may be substituted with substituent group C, and a substituent It is selected from the substituent group consisting of the heterocyclic alkyl which may be substituted by the group group C,
R ^C7 and R ^C8 , and R ^C9 and R ^C10 may be taken together with adjacent atoms to form a heterocycle, and Z is a single bond or a linear or branched alkylene. And

1) When B ¹ is NR ² and B ² is CR ^3a R ^3b , R ^3b and R ⁴ are combined with adjacent atoms to form a heterocyclic ring which may be substituted by Substituent Group D Further, the heterocyclic ring may form a bridge, or R ^3a and R ^3b may be a carbocyclic or heterocyclic ring optionally substituted with substituent group D together with the adjacent atoms Or 2) when B ¹ is CR ^3a R ^3b , and B ² is NR ² , R ² and R ⁴ together with the adjacent atoms are substituted with substituent group D And may form a heterocyclic ring, and the heterocyclic ring may further form a bridge;

Substituent group C: halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkyloxy, alkynyloxy, alkylthio, hydroxyalkyl, carbocyclic group, heterocyclic group, Oxo substituted heterocyclic group, carbocyclic alkyloxy, carbocyclic oxyalkyl, carbocyclic alkyloxyalkyl, heterocyclic alkyloxy, heterocyclic oxyalkyl, heterocyclic alkyloxyalkyl, haloalkyloxy, alkyloxyalkyl, alkyloxyalkyloxy , Alkylcarbonyl, alkylcarbonyloxy, alkyloxycarbonyl, alkylamino, alkylcarbonylamino, haloalkylcarbonylamino, alkylaminocarbonyl, alkylsulfonyl, al Rusurufiniru, and alkylsulfonylamino;

Substituent group D: Halogen, cyano, hydroxy, carboxy, formyl, amino, oxo, nitro, alkyl, haloalkyl, alkyloxy, carbocyclic alkyloxy, heterocyclic alkyloxy, haloalkyloxy, alkyloxyalkyl, alkyloxyalkyloxy, Alkylcarbonyl, alkyloxycarbonyl, alkylamino, alkylcarbonylamino, alkylaminocarbonyl, alkylsulfonyl, alkylsulfonylamino, carbocyclic group which may be substituted by substituent group C, substituted by substituent group C Heterocyclic group, carbocyclic alkyl optionally substituted with substituent group C, and heterocyclic alkyl optionally substituted with substituent group C)
Or a pharmaceutically acceptable salt thereof.
The compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein R ¹ is hydrogen, carboxy, or -Z-N (R ^A1 ) (R ^A2 ).
The compound according to any one of claims 1 and 2, or a pharmaceutically acceptable salt thereof, wherein R ⁴ is hydrogen or alkyl optionally substituted with substituent group C.
R ² , R ^3a and R ^3b are each independently hydrogen, carboxy, cyano, alkyl optionally substituted with substituent group C, alkylcarbonyl optionally substituted with substituent group C, substituent group Alkyloxycarbonyl which may be substituted by C, carbocyclic group which may be substituted by substituent group C, carbocyclic alkyl which may be substituted by substituent group C, substituted by substituent group C A heterocyclic group which may be substituted, a heterocyclic alkyl which may be substituted with a substituent group C,
-Y-S-R ^B1 ,
-Z-S (= O) -R B2,
-Z-SO _2- R ^B3 ,
-C (= O) -C (= O) -R B4,
-C (= O) -N (R ^B5 ) (R ^B6 ),
-Z-C ( ^RB7 ) ( ^RB8 ) ( ^RB9 )
-Z-N ( ^RB11 ) -C (= O) -O- ^RB12 or -Z-N ( ^RB13 ) -C (= O) ^-RB14
The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof.
B ¹ is NR ² and B ² is CR ^3a R ^3b ,
R ² is alkyl may be substituted with a substituent group C, substituted with a substituent group C which may be carbocyclic group, which may be carbocyclic aryloxy substituted with a substituent group C, substituents A heterocyclic group which may be substituted by group C, a carbocyclic alkyl which may be substituted by a substituent group C, a heterocyclic alkyl which may be substituted by a substituent group C, or -Z-C ( R ^B7 ) (R ^B8 ) (R ^B9 ),
The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein R ^3a is hydrogen and R ^3b is hydrogen or alkyl optionally substituted with substituent group C. .
B ¹ is NR ² and B ² is CR ^3a R ^3b ,
R ² is alkyl may be substituted with a substituent group C, substituted with a substituent group C which may be carbocyclic group, which may be carbocyclic aryloxy substituted with a substituent group C, substituents A heterocyclic group which may be substituted by group C, a carbocyclic alkyl which may be substituted by a substituent group C, a heterocyclic alkyl which may be substituted by a substituent group C, or -Z-C ( R ^B7 ) (R ^B8 ) (R ^B9 ),
And R ^3a is hydrogen, and R ^3b and R ⁴ together with the adjacent atoms form a heterocyclic ring which may be substituted with Substituent Group D, and further the heterocyclic ring forms a bridge. Good,
The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof.
R ² is a group shown below:

(Wherein, R ^E6 is selected from Substituent Group C, and m is an integer of 0 or 1 or more,
Wherein the m R ^{E 6 s} are the same or different group selected from Substituent Group C), or the compound according to claim 5 or 6, or a pharmaceutically acceptable salt thereof.
B ¹ is CR ^3a R ^3b and B ² is NR ² ,
R ² is hydrogen or alkyl optionally substituted with substituent group C,
R ^3a is hydrogen, R ^3b is ^optionally substituted alkyl group C, carbocyclic group ^optionally substituted group C, substituted group C Good carbocyclic ring oxyalkyl, heterocyclic group optionally substituted with substituent group C, carbocyclic alkyl optionally substituted with substituent group C, heterocyclic ring optionally substituted with substituent group C Alkyl, or -Z-C (R ^B7 ) (R ^B8 ) (R ^B9 )
The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof.
B ¹ is CR ^3a R ^3b and B ² is NR ² ,
R ^3a is hydrogen,
R ^{3 b} is alkyl ^optionally substituted with substituent group C, carbocyclic group ^optionally substituted with substituent group C, carbocyclic oxyalkyl optionally substituted with substituent group C, substituent A heterocyclic group which may be substituted by group C, a carbocyclic alkyl which may be substituted by a substituent group C, a heterocyclic alkyl which may be substituted by a substituent group C, or -Z-C ( R ^B7 ) (R ^B8 ) (R ^B9 ), and R ² and R ⁴ together with the adjacent atoms form a heterocyclic ring which may be substituted by Substituent Group D, and further the heterocyclic ring May form crosslinks,
The compound according to any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof.
R ^3b is a group shown below:

(Wherein, R ^E6 is selected from Substituent Group C, and m is an integer of 0 or 1 or more,
Provided that the m R ^{E 6 s} are the same or different group selected from Substituent Group C) or the pharmaceutically acceptable salt thereof according to claim 8 or 9.
The substituent group D is halogen, alkyl, haloalkyl, alkyloxy, a carbocyclic group which may be substituted with a substituent group C, a heterocyclic group which may be substituted with a substituent group C, a substituent group The compound according to any one of claims 1, 6, or 9, or a pharmaceutically acceptable substance thereof, which is a carbocyclic alkyl optionally substituted by C, or a heterocyclic alkyl optionally substituted by substituent group C. Acceptable salt.
The compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein P is hydrogen.
P is a group forming a prodrug, and the group forming the prodrug is selected from the following formulas a) to ac);
^{a) -C (= O) -P} R0,
^{b) -C (= O) -P} R1,
c) -C (= O) -L- ^PR1 ,
d) -C (= O) -L-O-P ^R1 ,
e) -C (= O) -L-O-L-O-P ^R1 ,
f) -C (= O) -L-O-C (= O) -P ^R1 ,
g) -C (= O) -O- ^PR2 ,
h) -C (= O) -N (-K) ( ^PR2 ),
i) -C (= O) -O-L-O- ^PR2 ,
j) -C ( ^PR3 ) _2- O- ^PR4 ;
k) -C ( ^PR3 ) _2- O-L-O- ^PR4 ,
_{^{l) -C (P R3) 2}} -O-C (= O) -P R4,
m) -C ( ^PR3 ) _2- O-C (= O) -OP- ^R4 ,
_{^{n) -C (P R3) 2}} -O-C (= O) -N (-K) -P R4,
o) -C ( ^PR3 ) _2- O-C (= O) -O-L-O- ^PR4 ,
p) -C ( ^PR3 ) _2- OC (= O) -OLN ( ^PR4 ) ₂ ,
q) -C ( ^PR3 ) _2- OC (= O) -N (-K) -LO- ^PR4 ;
r) -C ( ^PR3 ) _2- OC (= O) -N (-K) -L-N ( ^PR4 ) ₂ ,
s) -C ( ^PR3 ) _2- O-C (= O) -O-L-O-L-O- ^PR4 ,
_{^{t) -C (P R3) 2}} -O-C (= O) -O-L-N (-K) -C (= O) -P R4,
u) -C ( ^PR3 ) ₂ -OP (= O) ( ^-PR5 ) ₂ ,
_{^{v) -C (P R3) 2}} -P R6,
w)-C (= N ⁺ ( ^PR7 ) ₂ ) (-N ( ^PR7 ) ₂ ),
x) -C ( ^PR3 ) _2- C ( ^PR3 ) _2- C (= O) -O- ^PR2 ,
y) -C ( ^PR3 ) _2- N (-K) -C (= O) -O- ^PR2 ,
z)-P (= O) ( ^-PR8 ) ( ^-PR9 ),
^{_{aa) -S (= O) 2}} -P R10,
^{ab) -P R11,} and _{^{ac) -C (P R3) 2}} -C (P R3) 2 -O-P R2,
Wherein L is linear or branched alkylene, or linear or branched alkenylene,
K is hydrogen or alkyl optionally substituted with substituent group A,
P ^R0 is an alkyl which may be substituted with the substituent group A or an alkenyl which may be substituted with the substituent group A,
P ^{R 1} represents a carbocyclic group which may be substituted with substituent group A, a heterocyclic group which may be substituted with substituent group A, an alkylamino which may be substituted with substituent group A, Or alkylsulfanyl optionally substituted with substituent group A,
P ^{R 2} is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, heterocyclic alkyl which may be substituted by substituent group A, or trialkylsilyl;
P ^R3 is independently hydrogen or alkyl,
P ^{R 4} each independently represents an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a complex which may be substituted with the substituent group A Cyclic group, alkylamino which may be substituted with substituent group A, carbocyclic alkyl which may be substituted with substituent group A, heterocyclic alkyl which may be substituted with substituent group A, or tri It is alkylsilyl and
And P ^R5 is independently hydroxy or OB n
P ^R6 is a carbocyclic group which may be substituted with the substituent group A or a heterocyclic group which may be substituted with the substituent group A,
Each P ^R7 is independently an alkyl which may be substituted with Substituent Group A,
^{PR 8} is alkyloxy optionally substituted with substituent group A,
^{PR 9} is alkyloxy optionally substituted with substituent group A, alkylamino optionally substituted with substituent group A, carbocyclic ring oxy optionally substituted with substituent group A, substituent group A heterocyclic oxy which may be substituted by A, a carbocyclic amino which may be substituted by a substituent group A, or a heterocyclic amino which may be substituted by a substituent group A,
P ^R8 and P ^R9 may be taken together with the adjacent phosphorus atom to form a heterocyclic ring which may be substituted with Substituent Group A,
P ^R10 is an alkyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, a heterocyclic group which may be substituted with the substituent group A, or Carbocyclic alkyl which may be substituted by group A, or heterocyclic alkyl which may be substituted by substituent group A, and
P ^{R 11} represents an alkyl which may be substituted with the substituent group A, an alkenyl which may be substituted with the substituent group A, a carbocyclic group which may be substituted with the substituent group A, or a substituent group A heterocyclic group optionally substituted by A.
Substituent group A: oxo, alkyl, hydroxyalkyl, amino, alkylamino, carbocyclic group, heterocyclic group, carbocyclic alkyl, alkylcarbonyl, halogen, hydroxy, carboxy, alkylcarbonylamino, alkylcarbonylaminoalkyl, alkyl Carbonyloxy, alkyloxycarbonyl, alkyloxycarbonylalkyl, alkyloxycarbonyloxy, alkylaminocarbonyloxy, alkylaminoalkyl, alkyloxy, cyano, nitro, azide, alkylsulfonyl, trialkylsilyl and phospho) 11. The compound according to any one of to 11, or a pharmaceutically acceptable salt thereof.
The antiviral agent containing the compound in any one of Claims 1-13, its pharmaceutically acceptable salt, or those solvates.
The antiviral agent according to claim 14, which has an anti-influenza activity.