JPWO2021178920A5 - - Google Patents

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JPWO2021178920A5
JPWO2021178920A5 JP2022552714A JP2022552714A JPWO2021178920A5 JP WO2021178920 A5 JPWO2021178920 A5 JP WO2021178920A5 JP 2022552714 A JP2022552714 A JP 2022552714A JP 2022552714 A JP2022552714 A JP 2022552714A JP WO2021178920 A5 JPWO2021178920 A5 JP WO2021178920A5
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JP2023516073A (en
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Priority claimed from PCT/US2021/021240 external-priority patent/WO2021178920A1/en
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上記の発明は、理解を明確にする目的で説明及び例として幾らか詳細に記載しているが、当業者には、本発明の教示を踏まえることで、添付の特許請求の範囲に規定される本発明の趣旨又は範囲を逸脱することなく、或る特定の変更及び修正をそれに加えることができることが容易に明らかである。さらに、当業者であれば、日常実験を用いるだけで、本明細書に記載される特定の実施形態及び方法に対する多くの均等物を認識するか、又は確かめることができる。かかる均等物は、本願の範囲に包含されることが意図される。
項１
式Ｉ、式ＩＩ、式ＩＩＩ、式ＩＶ、式Ｖ及び式ＶＩ：
（式中、
各ａは独立して０、１又は２であり、
各ｙは独立して０、１又は２であり、
Ｘ ３ 、Ｘ ４ 、Ｘ ５ 及びＸ ６ はＮ、ＣＨ及びＣＲ ３ からなる群から選択され、ここでＸ ３ 、Ｘ ４ 、Ｘ ５ 及びＸ ６ の３つ以下がＮであり、
Ｘ ７ はＮ又はＣＨであり、
Ｘ ８ 及びＸ ９ は、いずれの場合にも各々独立してＮ及びＣＨからなる群から選択され、ここでＸ ８ 又はＸ ９ の少なくとも１つがＣＨであり、
Ｘ １２ はＮ、Ｏ及びＳから独立して選択される１個、２個又は３個の原子を有する５員のヘテロアリール基であり、ここでＸ １２ は、Ｒ ３ から独立して選択される１つ、２つ又は３つの基で任意に置換され、
Ｘ １７ はアリール、ヘテロアリール、二環又はシクロアルキルであり、その各々がＲ ３ から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換され、
Ｑ １ は、いずれの場合にも独立してＮＨ、Ｎ（アルキル）、Ｎ（ハロアルキル）、ＣＨ ２ 、Ｏ及びＳからなる群から選択され、ここでＸ ７ がＮである場合、Ｑ １ はＣＨ ２ であり、
Ｒは、いずれの場合にも独立して水素、Ｃ １ ～Ｃ ４ ハロアルキル、Ｃ １ ～Ｃ ４ アルキル、フッ素、塩素、臭素、ヨウ素、ＣＨ ２ Ｆ、ＣＨＦ ２ 、ＣＦ ３ 、ＣＨ ２ Ｃｌ、ＣＨＣｌ ２ 、ＣＣｌ ３ 、ＣＨ ２ Ｂｒ、ＣＨＢｒ ２ 及びＣＢｒ ３ からなる群から選択され、
Ｒ １ は水素、Ｃ １ ～Ｃ ４ アルキル、Ｃ １ ～Ｃ ４ ハロアルキル又はシクロアルキルであり、
Ｒ ３ は、いずれの場合にも独立して水素、ヒドロキシル、アルコキシ、Ｃ １ ～Ｃ ４ アルキル、Ｃ １ ～Ｃ ４ ハロアルキル、シクロアルキル、フッ素、塩素、臭素及びヨウ素からなる群から選択され、
ＢはＢ １ 及びＢ ２ から選択され、
Ｂ １ は、
からなる群から選択され、
Ｂ ２ は、
からなる群から選択され、
Ｘ １０ はＣ（Ｒ ７ ） ２ 、Ｃ（Ｏ）若しくはＯであり、
Ｘ １１ は複素環、ヘテロアリール、アリール、シクロアルキル若しくは二環であり、このＸ １１ 基の各々がＲ ３ から独立して選択される１つ、２つ、３つ若しくは４つの基で任意に置換されるか、
又はＸ １０ 及びＸ １１ が一緒に、
を形成し、
Ｘ １３ 、Ｘ １４ 、Ｘ １５ 及びＸ １６ は独立してＮ、ＣＨ及びＣＲ ４ からなる群から選択され、ここでＸ １３ 、Ｘ １４ 、Ｘ １５ 及びＸ １６ の３つ以下がＮであり、
各Ｒ ４ は独立して水素、アリール、ヘテロアリール、Ｃ １ ～Ｃ ４ アルコキシ、Ｃ １ ～Ｃ ４ ハロアルキル、Ｃ １ ～Ｃ ４ ハロアルコキシ、Ｃ １ ～Ｃ ４ アルキル、フッ素、塩素、臭素及びヨウ素から選択され、
ここで、隣接した炭素原子上の２つのＲ ４ 基が任意に結合して縮合環を形成してもよく、該縮合環は１つ、２つ又は３つのＲ置換基で任意に置換され、このため、
の非限定的な例としては、２つのＲ ４ 基が結合してピロールを形成する、
が挙げられ、
Ｒ ５ は水素、Ｃ １ ～Ｃ ４ アルキル、アリル、クロチル、アルケニル、アルキニル、ハロアルキル又はシクロアルキルであり、
各Ｒ ６ は独立して水素、Ｃ １ ～Ｃ ４ アルコキシ、Ｃ １ ～Ｃ ４ アルキル、Ｃ １ ～Ｃ ４ ハロアルキル、フッ素、塩素、臭素及びヨウ素から選択され、
各Ｒ ７ は独立して水素又はＣ １ ～Ｃ ４ アルキルであり、
Ｒ ８ は水素、Ｃ １ ～Ｃ ４ アルキル、アリル、クロチル、アルケニル、アルキニル、ハロアルキル又はシクロアルキルであり、
Ｌは二価連結基である）から選択される化合物又はその薬学的に許容可能な塩。
項２
Ｌが式：
（式中、
Ｘ １ 及びＸ ２ は、いずれの場合にも独立して結合、複素環、ＮＲ ２ 、Ｃ（Ｒ ２ ） ２ 、Ｏ、Ｃ（Ｏ）及びＳから選択され、
Ｒ ２ は、いずれの場合にも独立して水素、アルキル、脂肪族、ヘテロ脂肪族、複素環、アリール、ヘテロアリール、－Ｃ（Ｏ）Ｈ、－Ｃ（Ｏ）ＯＨ、－Ｃ（Ｏ）アルキル、－Ｃ（Ｏ）Ｏアルキル、－Ｃ（Ｏ）（脂肪族、アリール、ヘテロ脂肪族又はヘテロアリール）、－Ｃ（Ｏ）Ｏ（脂肪族、アリール、ヘテロ脂肪族又はヘテロアリール）、アルケン及びアルキンからなる群から選択され、
Ｒ ２０ 、Ｒ ２１ 、Ｒ ２２ 、Ｒ ２３ 及びＲ ２４ は、いずれの場合にも独立して結合、アルキル、－Ｃ（Ｏ）－、－Ｃ（Ｏ）Ｏ－、－ＯＣ（Ｏ）－、－ＳＯ ２ －、－Ｓ（Ｏ）－、－Ｃ（Ｓ）－、－Ｃ（Ｏ）ＮＲ ２ －、－ＮＲ ２ Ｃ（Ｏ）－、－Ｏ－、－Ｓ－、－ＮＲ ２ －、－Ｃ（Ｒ ４０ Ｒ ４０ ）－、－Ｐ（Ｏ）（ＯＲ ２６ ）Ｏ－、－Ｐ（Ｏ）（ＯＲ ２６ ）－、二環、アルケン、アルキン、ハロアルキル、アルコキシ、アリール、複素環、脂肪族、ヘテロ脂肪族、ヘテロアリール、乳酸、グリコール酸及び炭素環からなる群から選択され、その各々がＲ ４０ から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換され、
Ｒ ２６ は、いずれの場合にも独立して水素、アルキル、アリールアルキル、ヘテロアリールアルキル、アルケン、アルキン、アリール、ヘテロアリール、複素環、脂肪族及びヘテロ脂肪族からなる群から選択され、
Ｒ ４０ は、いずれの場合にも独立して水素、アルキル、アルケン、アルキン、フルオロ、ブロモ、クロロ、ヒドロキシル、アルコキシ、アジド、アミノ、シアノ、－ＮＨ（アルキルを含む脂肪族）、－Ｎ（アルキルを含む脂肪族） ２ 、－ＮＨＳＯ ２ （アルキルを含む脂肪族）、－Ｎ（アルキルを含む脂肪族）ＳＯ ２ アルキル、－ＮＨＳＯ ２ （アリール、ヘテロアリール又は複素環）、－Ｎ（アルキル）ＳＯ ２ （アリール、ヘテロアリール又は複素環）、－ＮＨＳＯ ２ アルケニル、－Ｎ（アルキル）ＳＯ ２ アルケニル、－ＮＨＳＯ ２ アルキニル、－Ｎ（アルキル）ＳＯ ２ アルキニル、ハロアルキル、脂肪族、ヘテロ脂肪族、アリール、ヘテロアリール、複素環及びシクロアルキルからなる群から選択される）のリンカーである、項１に記載の化合物。
項３
式：
のものである、項１に記載の化合物。
項４
Ｘ ８ がＮであり、Ｘ ９ がＣＨである、項３に記載の化合物。
項５
Ｘ ８ がＣＨであり、Ｘ ９ がＮである、項３に記載の化合物。
項６
Ｘ ８ がＣＨであり、Ｘ ９ がＣＨである、項３に記載の化合物。
項７
が、
である、項３～６のいずれか一項に記載の化合物。
項８
が、
である、項３～６のいずれか一項に記載の化合物。
項９
が、
である、項３～６のいずれか一項に記載の化合物。
項１０
が、
である、項３～９のいずれか一項に記載の化合物。
項１１
ＲがＣ １ ～Ｃ ４ ハロアルキル、Ｃ １ ～Ｃ ４ アルキル、フッ素、塩素又は臭素である、項３～１１のいずれか一項に記載の化合物。
項１２
Ｒがフッ素である、項３～１１のいずれか一項に記載の化合物。
項１３
式：
のものである、項１に記載の化合物。
項１４
Ｘ １７ がＲ ３ から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換されるアリール基である、項１３に記載の化合物。
項１５
Ｘ １７ がフェニルである、項１４に記載の化合物。
項１６
Ｘ １７ がヘテロアリール基又はシクロアルキル基であり、その各々がＲ ３ から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換される、項１３に記載の化合物。
項１７
Ｑ １ がＮＨであり、Ｘ ７ がＣＨである、項３～１６のいずれか一項に記載の化合物。
項１８
Ｑ １ がＯであり、Ｘ ７ がＣＨである、項３～１６のいずれか一項に記載の化合物。
項１９
Ｑ １ がＮ（ＣＨ ３ ）であり、Ｘ ７ がＣＨである、項３～１６のいずれか一項に記載の化合物。
項２０
式：
のものである、項１に記載の化合物。
項２１
Ｘ ３ がＣＲ ３ である、項３～２０のいずれか一項に記載の化合物。
項２２
Ｘ ３ がＮである、項３～２０のいずれか一項に記載の化合物。
項２３
Ｘ ３ がＣＨである、項３～２０のいずれか一項に記載の化合物。
項２４
Ｘ ３ がＣＦである、項３～２０のいずれか一項に記載の化合物。
項２５
Ｘ ３ がＣ（ＣＦ ３ ）である、項３～２０のいずれか一項に記載の化合物。
項２６
Ｘ ３ がＣ（Ｃｌ）である、項３～２０のいずれか一項に記載の化合物。
項２７
Ｘ ５ がＣＲ ３ である、項３～２６のいずれか一項に記載の化合物。
項２８
Ｘ ５ がＮである、項３～２６のいずれか一項に記載の化合物。
項２９
Ｘ ５ がＣＨである、項３～２６のいずれか一項に記載の化合物。
項３０
Ｘ ５ がＣＦである、項３～２６のいずれか一項に記載の化合物。
項３１
Ｘ ５ がＣ（ＣＦ ３ ）である、項３～２６のいずれか一項に記載の化合物。
項３２
Ｘ ５ がＣ（Ｃｌ）である、項３～２６のいずれか一項に記載の化合物。
項３３
式：
のものである、項１に記載の化合物。
項３４
Ｒ １ が水素である、項３３に記載の化合物。
項３５
Ｒ １ がＣＨ ３ である、項３３に記載の化合物。
項３６
Ｘ ４ がＣＲ ３ である、項３～３５のいずれか一項に記載の化合物。
項３７
Ｘ ４ がＮである、項３～３５のいずれか一項に記載の化合物。
項３８
Ｘ ４ がＣＨである、項３～３５のいずれか一項に記載の化合物。
項３９
Ｘ ４ がＣＦである、項３～３５のいずれか一項に記載の化合物。
項４０
Ｘ ４ がＣ（ＣＦ ３ ）である、項３～３５のいずれか一項に記載の化合物。
項４１
Ｘ ４ がＣ（Ｃｌ）である、項３～３５のいずれか一項に記載の化合物。
項４２
Ｘ ６ がＣＲ ３ である、項３～４１のいずれか一項に記載の化合物。
項４３
Ｘ ６ がＣＨである、項３～４１のいずれか一項に記載の化合物。
項４４
Ｘ ６ がＣＦである、項３～４１のいずれか一項に記載の化合物。
項４５
Ｘ ６ がＣ（ＣＦ ３ ）である、項３～４１のいずれか一項に記載の化合物。
項４６
Ｘ ６ がＣ（Ｃｌ）である、項３～４１のいずれか一項に記載の化合物。
項４７
式：
のものである、項１に記載の化合物。
項４８
Ｑ １ がＮＨであり、Ｘ ７ がＣＨである、項４７に記載の化合物。
項４９
Ｑ １ がＯであり、Ｘ ７ がＣＨである、項４７に記載の化合物。
項５０
Ｑ １ がＮ（ＣＨ ３ ）であり、Ｘ ７ がＣＨである、項４７に記載の化合物。
項５１
Ｘ １２ がＮから独立して選択される１個、２個又は３個の原子を有する５員のヘテロアリール基であり、ここでＸ １２ はＲ ３ から独立して選択される１つ、２つ又は３つの基で任意に置換される、項４７～５０のいずれか一項に記載の化合物。
項５２
Ｘ １２ がフランであり、ここでＸ １２ はＲ ３ から独立して選択される１つ、２つ又は３つの基で任意に置換される、項４７～５０のいずれか一項に記載の化合物。
項５３
ＢがＢ １ である、項３～５５のいずれか一項に記載の化合物。
項５４
Ｂ １ が、
である、項５３に記載の化合物。
項５５
Ｒ ５ が水素である、項５４に記載の化合物。
項５６
Ｒ ５ がメチルである、項５４に記載の化合物。
項５７
Ｂ １ が、
である、項５３に記載の化合物。
項５８
Ｂ １ が、
である、項５３に記載の化合物。
項５９
Ｂ １ が、
である、項５３に記載の化合物。
項６０
ＢがＢ ２ である、項３～５２のいずれか一項に記載の化合物。
項６１
式：
のものである、項１に記載の化合物。
項６２
Ｑ １ がＮＨであり、Ｘ ７ がＣＨである、項６１に記載の化合物。
項６３
Ｑ １ がＯであり、Ｘ ７ がＣＨである、項６１に記載の化合物。
項６４
Ｑ １ がＮ（ＣＨ ３ ）であり、Ｘ ７ がＣＨである、項６１に記載の化合物。
項６５
Ｘ ３ がＣＲ ３ である、項６１～６４のいずれか一項に記載の化合物。
項６６
Ｘ ３ がＮである、項６１～６４のいずれか一項に記載の化合物。
項６７
Ｘ ３ がＣＨである、項６１～６４のいずれか一項に記載の化合物。
項６８
Ｘ ３ がＣＦである、項６１～６４のいずれか一項に記載の化合物。
項６９
Ｘ ３ がＣ（ＣＦ ３ ）である、項６１～６４のいずれか一項に記載の化合物。
項７０
Ｘ ３ がＣ（Ｃｌ）である、項６１～６４のいずれか一項に記載の化合物。
項７１
Ｘ ５ がＣＲ ３ である、項６１～７０のいずれか一項に記載の化合物。
項７２
Ｘ ５ がＮである、項６１～７０のいずれか一項に記載の化合物。
項７３
Ｘ ５ がＣＨである、項６１～７０のいずれか一項に記載の化合物。
項７４
Ｘ ５ がＣＦである、項６１～７０のいずれか一項に記載の化合物。
項７５
Ｘ ５ がＣ（ＣＦ ３ ）である、項６１～７０のいずれか一項に記載の化合物。
項７６
Ｘ ５ がＣ（Ｃｌ）である、項６１～７０のいずれか一項に記載の化合物。
項７７
Ｘ ４ がＣＲ ３ である、項６１～７６のいずれか一項に記載の化合物。
項７８
Ｘ ４ がＮである、項６１～７６のいずれか一項に記載の化合物。
項７９
Ｘ ４ がＣＨである、項６１～７６のいずれか一項に記載の化合物。
項８０
Ｘ ４ がＣＦである、項６１～７６のいずれか一項に記載の化合物。
項８１
Ｘ ４ がＣ（ＣＦ ３ ）である、項６１～７６のいずれか一項に記載の化合物。
項８２
Ｘ ４ がＣ（Ｃｌ）である、項６１～７６のいずれか一項に記載の化合物。
項８３
Ｘ ６ がＣＲ ３ である、項６１～７６のいずれか一項に記載の化合物。
項８４
Ｘ ６ がＣＨである、項６１～７６のいずれか一項に記載の化合物。
項８５
Ｘ ６ がＣＦである、項６１～７６のいずれか一項に記載の化合物。
項８６
Ｘ ６ がＣ（ＣＦ ３ ）である、項６１～７６のいずれか一項に記載の化合物。
項８７
Ｘ ６ がＣ（Ｃｌ）である、項６１～７６のいずれか一項に記載の化合物。
項８８
Ｂ ２ が、
である、項６０～８７のいずれか一項に記載の化合物。
項８９
Ｒ ５ が水素である、項８８に記載の化合物。
項９０
Ｒ ５ がメチルである、項８８に記載の化合物。
項９１
Ｂ ２ が、
である、項６０～８７のいずれか一項に記載の化合物。
項９２
Ｂ ２ が、
である、項６０～８７のいずれか一項に記載の化合物。
項９３
Ｂ ２ が、
である、項６０～８７のいずれか一項に記載の化合物。
項９４
Ｘ １１ が複素環であり、このＸ １１ 基の各々がＲ ３ から独立して選択される１つ、２つ、３つ又は４つの基で任意に置換される、項６０～９３のいずれか一項に記載の化合物。
項９５
Ｘ １１ が二環であり、このＸ １１ 基の各々がＲ ３ から独立して選択される１つ、２つ、３つ又は４つの基で任意に置換される、項６０～９３のいずれか一項に記載の化合物。
項９６
Ｘ １１ がヘテロアリール、アリール又はシクロアルキルであり、このＸ １１ 基の各々がＲ ３ から独立して選択される１つ、２つ、３つ又は４つの基で任意に置換される、項６０～９３のいずれか一項に記載の化合物。
項９７
Ｘ １１ が、
から選択される、項６０～９３のいずれか一項に記載の化合物。
項９８
Ｘ １１ が、
から選択される、項６０～９３のいずれか一項に記載の化合物。
項９９
Ｘ １０ 及びＸ １１ が一緒に、
を形成する、項６０～９３のいずれか一項に記載の化合物。
項１００
Ｘ １０ 及びＸ １１ が一緒に、
を形成する、項６０～９３のいずれか一項に記載の化合物。
項１０１
Ｘ １０ がＣ（Ｒ ７ ） ２ である、項３～９８のいずれか一項に記載の化合物。
項１０２
Ｘ １０ がＣＨ ２ である、項３～９８のいずれか一項に記載の化合物。
項１０３
Ｘ １０ がＣ（Ｏ）である、項３～９８のいずれか一項に記載の化合物。
項１０４
Ｘ １０ がＯである、項３～９８のいずれか一項に記載の化合物。
項１０５
Ｘ １３ がＣＲ ３ である、項３～１０４のいずれか一項に記載の化合物。
項１０６
Ｘ １３ がＮである、項３～１０４のいずれか一項に記載の化合物。
項１０７
Ｘ １３ がＣＨである、項３～１０４のいずれか一項に記載の化合物。
項１０８
Ｘ １３ がＣＦである、項３～１０４のいずれか一項に記載の化合物。
項１０９
Ｘ １３ がＣ（ＣＦ ３ ）である、項３～１０４のいずれか一項に記載の化合物。
項１１０
Ｘ １３ がＣ（Ｃｌ）である、項３～１０４のいずれか一項に記載の化合物。
項１１１
Ｘ １４ がＣＲ ３ である、項３～１１０のいずれか一項に記載の化合物。
項１１２
Ｘ １４ がＮである、項３～１１０のいずれか一項に記載の化合物。
項１１３
Ｘ １４ がＣＨである、項３～１１０のいずれか一項に記載の化合物。
項１１４
Ｘ １４ がＣＦである、項３～１１０のいずれか一項に記載の化合物。
項１１５
Ｘ １４ がＣ（ＣＦ ３ ）である、項３～１１０のいずれか一項に記載の化合物。
項１１６
Ｘ １４ がＣ（Ｃｌ）である、項３～１１０のいずれか一項に記載の化合物。
項１１７
Ｘ １５ がＣＲ ３ である、項３～１１６のいずれか一項に記載の化合物。
項１１８
Ｘ １５ がＮである、項３～１１６のいずれか一項に記載の化合物。
項１１９
Ｘ １５ がＣＨである、項３～１１６のいずれか一項に記載の化合物。
項１２０
Ｘ １５ がＣＦである、項３～１１６のいずれか一項に記載の化合物。
項１２１
Ｘ １５ がＣ（ＣＦ ３ ）である、項３～１１６のいずれか一項に記載の化合物。
項１２２
Ｘ １５ がＣ（Ｃｌ）である、項３～１１６のいずれか一項に記載の化合物。
項１２３
Ｘ １６ がＣＲ ３ である、項３～１２２のいずれか一項に記載の化合物。
項１２４
Ｘ １６ がＣＨである、項３～１２２のいずれか一項に記載の化合物。
項１２５
Ｘ １６ がＣＦである、項３～１２２のいずれか一項に記載の化合物。
項１２６
Ｘ １６ がＣ（ＣＦ ３ ）である、項３～１２２のいずれか一項に記載の化合物。
項１２７
Ｘ １６ がＣ（Ｃｌ）である、項３～１２２のいずれか一項に記載の化合物。
項１２８
Ｒ ８ が水素である、項３～１２７のいずれか一項に記載の化合物。
項１２９
Ｒ ８ がメチルである、項３～１２７のいずれか一項に記載の化合物。
項１３０
Ｌが式：
（式中、
Ｘ １ 及びＸ ２ は、いずれの場合にも独立して結合、複素環、ＮＲ ２ 、Ｃ（Ｒ ２ ） ２ 、Ｏ、Ｃ（Ｏ）及びＳから選択され、
Ｒ ２ は、いずれの場合にも独立して水素、アルキル、脂肪族、ヘテロ脂肪族、複素環、アリール、ヘテロアリール、－Ｃ（Ｏ）Ｈ、－Ｃ（Ｏ）ＯＨ、－Ｃ（Ｏ）アルキル、－Ｃ（Ｏ）Ｏアルキル、－Ｃ（Ｏ）（脂肪族、アリール、ヘテロ脂肪族又はヘテロアリール）、－Ｃ（Ｏ）Ｏ（脂肪族、アリール、ヘテロ脂肪族又はヘテロアリール）、アルケン及びアルキンからなる群から選択され、
Ｒ ２０ 、Ｒ ２１ 、Ｒ ２２ 、Ｒ ２３ 及びＲ ２４ は、いずれの場合にも独立して結合、アルキル、－Ｃ（Ｏ）－、－Ｃ（Ｏ）Ｏ－、－ＯＣ（Ｏ）－、－ＳＯ ２ －、－Ｓ（Ｏ）－、－Ｃ（Ｓ）－、－Ｃ（Ｏ）ＮＲ ２ －、－ＮＲ ２ Ｃ（Ｏ）－、－Ｏ－、－Ｓ－、－ＮＲ ２ －、－Ｃ（Ｒ ４０ Ｒ ４０ ）－、－Ｐ（Ｏ）（ＯＲ ２６ ）Ｏ－、－Ｐ（Ｏ）（ＯＲ ２６ ）－、アルケン、アルキン、ハロアルキル、アルコキシ、アリール、複素環、脂肪族、ヘテロ脂肪族、ヘテロアリール、乳酸、グリコール酸及び炭素環からなる群から選択され、その各々がＲ ４０ から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換され、
Ｒ ２６ は、いずれの場合にも独立して水素、アルキル、アリールアルキル、ヘテロアリールアルキル、アルケン、アルキン、アリール、ヘテロアリール、複素環、脂肪族及びヘテロ脂肪族からなる群から選択され、
Ｒ ４０ は、いずれの場合にも独立して水素、アルキル、アルケン、アルキン、フルオロ、ブロモ、クロロ、ヒドロキシル、アルコキシ、アジド、アミノ、シアノ、－ＮＨ（アルキルを含む脂肪族）、－Ｎ（アルキルを含む脂肪族） ２ 、－ＮＨＳＯ ２ （アルキルを含む脂肪族）、－Ｎ（アルキルを含む脂肪族）ＳＯ ２ アルキル、－ＮＨＳＯ ２ （アリール、ヘテロアリール又は複素環）、－Ｎ（アルキル）ＳＯ ２ （アリール、ヘテロアリール又は複素環）、－ＮＨＳＯ ２ アルケニル、－Ｎ（アルキル）ＳＯ ２ アルケニル、－ＮＨＳＯ ２ アルキニル、－Ｎ（アルキル）ＳＯ ２ アルキニル、ハロアルキル、脂肪族、ヘテロ脂肪族、アリール、ヘテロアリール、複素環及びシクロアルキルからなる群から選択される）のリンカーである、項３～１２９のいずれか一項に記載の化合物。
項１３１
Ｌが式：
のリンカーである、項１３０に記載の化合物。
項１３２
Ｘ １ が結合である、項１３０又は１３１に記載の化合物。
項１３３
Ｘ １ が複素環である、項１３０又は１３１に記載の化合物。
項１３４
Ｘ １ がＮＲ ２ である、項１３０又は１３１に記載の化合物。
項１３５
Ｘ １ がＣ（Ｏ）である、項１３０又は１３１に記載の化合物。
項１３６
Ｘ ２ が結合である、項１３０～１３５のいずれか一項に記載の化合物。
項１３７
Ｘ ２ が複素環である、項１３０～１３５のいずれか一項に記載の化合物。
項１３８
Ｘ ２ がＮＲ ２ である、項１３０～１３５のいずれか一項に記載の化合物。
項１３９
Ｘ ２ がＣ（Ｏ）である、項１３０～１３５のいずれか一項に記載の化合物。
項１４０
Ｒ ２０ が結合である、項１３０～１３９のいずれか一項に記載の化合物。
項１４１
Ｒ ２０ がＣＨ ２ である、項１３０～１３９のいずれか一項に記載の化合物。
項１４２
Ｒ ２０ が複素環である、項１３０～１３９のいずれか一項に記載の化合物。
項１４３
Ｒ ２０ がアリールである、項１３０～１３９のいずれか一項に記載の化合物。
項１４４
Ｒ ２０ がフェニルである、項１３０～１３９のいずれか一項に記載の化合物。
項１４５
Ｒ ２０ が二環である、項１３０～１３９のいずれか一項に記載の化合物。
項１４６
Ｒ ２１ が結合である、項１３０～１４５のいずれか一項に記載の化合物。
項１４７
Ｒ ２１ がＣＨ ２ である、項１３０～１４５のいずれか一項に記載の化合物。
項１４８
Ｒ ２１ が複素環である、項１３０～１４５のいずれか一項に記載の化合物。
項１４９
Ｒ ２１ がアリールである、項１３０～１４５のいずれか一項に記載の化合物。
項１５０
Ｒ ２１ がフェニルである、項１３０～１４５のいずれか一項に記載の化合物。
項１５１
Ｒ ２１ が二環である、項１３０～１４５のいずれか一項に記載の化合物。
項１５２
Ｌが式：
のリンカーである、項１３０に記載の化合物。
項１５３
Ｒ ２２ が結合である、項１３０～１５２のいずれか一項に記載の化合物。
項１５４
Ｒ ２２ がＣＨ ２ である、項１３０～１５２のいずれか一項に記載の化合物。
項１５５
Ｒ ２２ が複素環である、項１３０～１５２のいずれか一項に記載の化合物。
項１５６
Ｒ ２２ がアリールである、項１３０～１５２のいずれか一項に記載の化合物。
項１５７
Ｒ ２２ がフェニルである、項１３０～１５２のいずれか一項に記載の化合物。
項１５８
Ｒ ２２ が二環である、項１３０～１５２のいずれか一項に記載の化合物。
項１５９
Ｌが式：
のリンカーである、項１３０に記載の化合物。
項１６０
Ｒ ２３ が結合である、項１３０～１５９のいずれか一項に記載の化合物。
項１６１
Ｒ ２３ がＣＨ ２ である、項１３０～１５９のいずれか一項に記載の化合物。
項１６２
Ｒ ２３ が複素環である、項１３０～１５９のいずれか一項に記載の化合物。
項１６３
Ｒ ２３ がアリールである、項１３０～１５９のいずれか一項に記載の化合物。
項１６４
Ｒ ２３ がフェニルである、項１３０～１５９のいずれか一項に記載の化合物。
項１６５
Ｒ ２３ が二環である、項１３０～１５９のいずれか一項に記載の化合物。
項１６６
Ｌが式：
のリンカーである、項１３０に記載の化合物。
項１６７
Ｒ ２４ が結合である、項１３０～１６６のいずれか一項に記載の化合物。
項１６８
Ｒ ２４ がＣＨ ２ である、項１３０～１６６のいずれか一項に記載の化合物。
項１６９
Ｒ ２４ が複素環である、項１３０～１６６のいずれか一項に記載の化合物。
項１７０
Ｒ ２４ がアリールである、項１３０～１６６のいずれか一項に記載の化合物。
項１７１
Ｒ ２４ がフェニルである、項１３０～１６６のいずれか一項に記載の化合物。
項１７２
Ｒ ２４ が二環である、項１３０～１６６のいずれか一項に記載の化合物。
項１７３
Ｒ ２４ がＣ（Ｏ）である、項１３０～１６６のいずれか一項に記載の化合物。
項１７４
Ｌが、
から選択される、項３～１７３のいずれか一項に記載の化合物。
項１７５
表１から選択される化合物又はその薬学的に許容可能な塩。
項１７６
表２から選択される化合物又はその薬学的に許容可能な塩。
項１７７
項１～１７６のいずれか一項に記載の化合物又はその薬学的に許容可能な塩と、薬学的に許容可能な賦形剤とを含む医薬組成物。
項１７８
任意に医薬組成物中の有効量の項１～１７６のいずれか一項に記載の化合物又はその薬学的に許容可能な塩を、それを必要とする患者に投与することを含む、ＢＲＤ９によって媒介される障害を治療する方法。
項１７９
前記患者がヒトである、項１７８に記載の方法。
項１８０
ＢＲＤ９媒介性障害の治療に使用される、任意に医薬組成物中の項１～１７６のいずれか一項に記載の化合物又はその薬学的に許容可能な塩。
項１８１
ＢＲＤ９媒介性障害の治療における、任意に医薬組成物中の項１～１７６のいずれか一項に記載の化合物又はその薬学的に許容可能な塩の使用。
項１８２
ＢＲＤ９媒介性障害の治療のための薬剤の製造における、任意に医薬組成物中の項１～１７６のいずれか一項に記載の化合物又はその薬学的に許容可能な塩の使用。 Although the above invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, those skilled in the art will appreciate that, in light of the teachings of this invention, the scope of the invention as set forth in the appended claims It will be readily apparent that certain changes and modifications may be made thereto without departing from the spirit or scope of the invention. Additionally, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments and methods described herein. Such equivalents are intended to be included within the scope of this application.
Item 1
Formula I, Formula II, Formula III, Formula IV, Formula V and Formula VI:
(In the formula,
each a is independently 0, 1 or 2,
each y is independently 0, 1 or 2;
X 3 ,X 4 ,X 5 and X 6 are N, CH and CR 3 is selected from the group consisting of, where X 3 ,X 4 ,X 5 and X 6 3 or less of are N,
X 7 is N or CH,
X 8 and X 9 are in each case independently selected from the group consisting of N and CH, where 8 or X 9 at least one of is CH,
X 12 is a 5-membered heteroaryl group having 1, 2 or 3 atoms independently selected from N, O and S, where X 12 is, R 3 optionally substituted with one, two or three groups independently selected from
X 17 is aryl, heteroaryl, bicyclic or cycloalkyl, each of which R 3 optionally substituted with one, two, three or four substituents independently selected from
Q 1 is, in each case, independently NH, N (alkyl), N (haloalkyl), CH 2 , O and S, where X 7 is N, then Q 1 is CH 2 and
R is in each case independently hydrogen, C 1 ～C 4 Haloalkyl, C 1 ～C 4 Alkyl, fluorine, chlorine, bromine, iodine, CH 2 F.CHF 2 , C.F. 3 , C.H. 2 Cl, CHCl 2 , CCl 3 , C.H. 2 Br, CHBr 2 and CBr 3 selected from the group consisting of
R 1 is hydrogen, C 1 ～C 4 alkyl, C 1 ～C 4 haloalkyl or cycloalkyl,
R 3 is in each case independently hydrogen, hydroxyl, alkoxy, C 1 ～C 4 alkyl, C 1 ～C 4 selected from the group consisting of haloalkyl, cycloalkyl, fluorine, chlorine, bromine and iodine;
B is B 1 and B 2 selected from
B 1 teeth,
selected from the group consisting of
B 2 teeth,
selected from the group consisting of
X 10 is C(R 7 ) 2 , C(O) or O,
X 11 is a heterocycle, heteroaryl, aryl, cycloalkyl or bicyclic; 11 Each of the groups is R 3 optionally substituted with one, two, three or four groups independently selected from;
or X 10 and X 11 together,
form,
X 13 ,X 14 ,X 15 and X 16 are independently N, CH and CR 4 selected from the group consisting of, where X 13 ,X 14 ,X 15 and X 16 3 or less of are N,
Each R 4 are independently hydrogen, aryl, heteroaryl, C 1 ～C 4 Alkoxy, C 1 ～C 4 Haloalkyl, C 1 ～C 4 Haloalkoxy, C 1 ～C 4 selected from alkyl, fluorine, chlorine, bromine and iodine,
Here, two R on adjacent carbon atoms 4 The groups may be optionally joined to form a fused ring, which fused ring is optionally substituted with one, two or three R substituents, such that
As a non-limiting example, two R 4 the groups combine to form pyrrole,
are mentioned,
R 5 is hydrogen, C 1 ～C 4 alkyl, allyl, crotyl, alkenyl, alkynyl, haloalkyl or cycloalkyl,
Each R 6 are independently hydrogen, C 1 ～C 4 Alkoxy, C 1 ～C 4 alkyl, C 1 ～C 4 selected from haloalkyl, fluorine, chlorine, bromine and iodine,
Each R 7 is independently hydrogen or C 1 ～C 4 is alkyl,
R 8 is hydrogen, C 1 ～C 4 alkyl, allyl, crotyl, alkenyl, alkynyl, haloalkyl or cycloalkyl,
L is a divalent linking group) or a pharmaceutically acceptable salt thereof.
Section 2
L is the formula:
(In the formula,
X 1 and X 2 is in each case independently a bond, a heterocycle, NR 2 ,C(R 2 ) 2 , O, C(O) and S;
R 2 is in each case independently hydrogen, alkyl, aliphatic, heteroaliphatic, heterocycle, aryl, heteroaryl, -C(O)H, -C(O)OH, -C(O)alkyl, -C(O)O alkyl, -C(O) (aliphatic, aryl, heteroaliphatic or heteroaryl), -C(O)O (aliphatic, aryl, heteroaliphatic or heteroaryl), alkenes and alkynes selected from the group consisting of
R 20 ,R 21 ,R 22 ,R 23 and R 24 is in each case independently a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO 2 -, -S(O)-, -C(S)-, -C(O)NR 2 -, -NR 2 C(O)-, -O-, -S-, -NR 2 -, -C(R 40 R 40 )-,-P(O)(OR 26 )O-, -P(O)(OR 26 )-, bicyclic, alkene, alkyne, haloalkyl, alkoxy, aryl, heterocyclic, aliphatic, heteroaliphatic, heteroaryl, lactic acid, glycolic acid, and carbocyclic, each of which R 40 optionally substituted with one, two, three or four substituents independently selected from
R 26 are in each case independently selected from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkene, alkyne, aryl, heteroaryl, heterocycle, aliphatic and heteroaliphatic;
R 40 is in each case independently hydrogen, alkyl, alkene, alkyne, fluoro, bromo, chloro, hydroxyl, alkoxy, azide, amino, cyano, -NH (aliphatic including alkyl), -N (aliphatic including alkyl) aliphatic) 2 ,-NHSO 2 (aliphatic containing alkyl), -N (aliphatic containing alkyl) SO 2 Alkyl, -NHSO 2 (aryl, heteroaryl or heterocycle), -N(alkyl)SO 2 (aryl, heteroaryl or heterocycle), -NHSO 2 Alkenyl, -N(alkyl)SO 2 alkenyl, -NHSO 2 Alkynyl, -N(alkyl)SO 2 The compound according to paragraph 1, which is a linker selected from the group consisting of alkynyl, haloalkyl, aliphatic, heteroaliphatic, aryl, heteroaryl, heterocycle and cycloalkyl.
Section 3
formula:
The compound according to item 1, which is
Section 4
X 8 is N and 9 The compound according to item 3, wherein is CH.
Item 5
X 8 is CH and 9 is N, the compound according to item 3.
Item 6
X 8 is CH and 9 The compound according to item 3, wherein is CH.
Section 7
but,
The compound according to any one of items 3 to 6, which is.
Section 8
but,
The compound according to any one of items 3 to 6, which is.
Section 9
but,
The compound according to any one of items 3 to 6, which is.
Item 10
but,
The compound according to any one of items 3 to 9, which is.
Item 11
R is C 1 ～C 4 Haloalkyl, C 1 ～C 4 The compound according to any one of paragraphs 3 to 11, which is alkyl, fluorine, chlorine or bromine.
Item 12
The compound according to any one of paragraphs 3 to 11, wherein R is fluorine.
Item 13
formula:
The compound according to item 1, which is
Section 14
X 17 is R 3 14. A compound according to paragraph 13, which is an aryl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from .
Item 15
X 17 15. The compound according to item 14, wherein is phenyl.
Section 16
X 17 is a heteroaryl group or a cycloalkyl group, each of which R 3 14. A compound according to paragraph 13, optionally substituted with 1, 2, 3 or 4 substituents independently selected from.
Section 17
Q 1 is NH and 7 17. The compound according to any one of paragraphs 3 to 16, wherein is CH.
Item 18
Q 1 is O and 7 17. The compound according to any one of paragraphs 3 to 16, wherein is CH.
Item 19
Q 1 is N(CH 3 ) and X 7 17. The compound according to any one of paragraphs 3 to 16, wherein is CH.
Section 20
formula:
The compound according to item 1, which is
Section 21
X 3 is CR 3 The compound according to any one of Items 3 to 20, which is.
Section 22
X 3 21. The compound according to any one of paragraphs 3 to 20, wherein N is N.
Item 23
X 3 21. The compound according to any one of paragraphs 3 to 20, wherein is CH.
Section 24
X 3 21. The compound according to any one of paragraphs 3 to 20, wherein is CF.
Section 25
X 3 is C (CF 3 ), the compound according to any one of Items 3 to 20.
Section 26
X 3 21. The compound according to any one of paragraphs 3 to 20, wherein is C(Cl).
Section 27
X 5 is CR 3 The compound according to any one of Items 3 to 26, which is.
Section 28
X 5 27. The compound according to any one of paragraphs 3 to 26, wherein N is N.
Section 29
X 5 27. The compound according to any one of paragraphs 3 to 26, wherein is CH.
Section 30
X 5 27. The compound according to any one of paragraphs 3 to 26, wherein is CF.
Item 31
X 5 is C (CF 3 ), the compound according to any one of Items 3 to 26.
Item 32
X 5 27. The compound according to any one of paragraphs 3 to 26, wherein is C(Cl).
Section 33
formula:
The compound according to item 1, which is
Item 34
R 1 34. The compound according to item 33, wherein is hydrogen.
Section 35
R 1 is CH 3 The compound according to item 33, which is.
Section 36
X 4 is CR 3 The compound according to any one of Items 3 to 35, which is.
Section 37
X 4 36. The compound according to any one of paragraphs 3 to 35, wherein is N.
Section 38
X 4 36. The compound according to any one of paragraphs 3 to 35, wherein is CH.
Section 39
X 4 36. The compound according to any one of paragraphs 3 to 35, wherein is CF.
Section 40
X 4 is C (CF 3 ), the compound according to any one of items 3 to 35.
Section 41
X 4 36. The compound according to any one of paragraphs 3 to 35, wherein is C(Cl).
Section 42
X 6 is CR 3 The compound according to any one of Items 3 to 41, which is.
Section 43
X 6 42. The compound according to any one of paragraphs 3 to 41, wherein is CH.
Section 44
X 6 42. The compound according to any one of paragraphs 3 to 41, wherein is CF.
Section 45
X 6 is C (CF 3 ), the compound according to any one of Items 3 to 41.
Section 46
X 6 42. The compound according to any one of paragraphs 3 to 41, wherein is C(Cl).
Section 47
formula:
The compound according to item 1, which is
Item 48
Q 1 is NH and 7 48. The compound according to item 47, wherein is CH.
Section 49
Q 1 is O and 7 48. The compound according to item 47, wherein is CH.
Item 50
Q 1 is N(CH 3 ) and X 7 48. The compound according to item 47, wherein is CH.
Section 51
X 12 is a 5-membered heteroaryl group having 1, 2 or 3 atoms independently selected from N, where X 12 is R 3 51. A compound according to any one of paragraphs 47 to 50, optionally substituted with one, two or three groups independently selected from.
Section 52
X 12 is a franc, where X 12 is R 3 51. A compound according to any one of paragraphs 47 to 50, optionally substituted with one, two or three groups independently selected from.
Section 53
B is B 1 The compound according to any one of Items 3 to 55, which is.
Item 54
B 1 but,
54. The compound according to item 53.
Section 55
R 5 55. The compound according to item 54, wherein is hydrogen.
Section 56
R 5 55. The compound according to item 54, wherein is methyl.
Section 57
B 1 but,
54. The compound according to item 53.
Section 58
B 1 but,
54. The compound according to item 53.
Section 59
B 1 but,
54. The compound according to item 53.
Section 60
B is B 2 The compound according to any one of Items 3 to 52, which is.
Section 61
formula:
The compound according to item 1, which is
Section 62
Q 1 is NH and 7 62. The compound according to item 61, wherein is CH.
Section 63
Q 1 is O and 7 62. The compound according to item 61, wherein is CH.
Item 64
Q 1 is N(CH 3 ) and X 7 62. The compound according to item 61, wherein is CH.
Item 65
X 3 is CR 3 The compound according to any one of Items 61 to 64, which is.
Section 66
X 3 is N, the compound according to any one of paragraphs 61 to 64.
Section 67
X 3 65. The compound according to any one of paragraphs 61 to 64, wherein is CH.
Section 68
X 3 65. The compound according to any one of paragraphs 61 to 64, wherein is CF.
Item 69
X 3 is C (CF 3 ), the compound according to any one of Items 61 to 64.
Section 70
X 3 65. The compound according to any one of paragraphs 61 to 64, wherein is C(Cl).
Section 71
X 5 is CR 3 The compound according to any one of Items 61 to 70, which is.
Section 72
X 5 is N, the compound according to any one of paragraphs 61 to 70.
Section 73
X 5 71. The compound according to any one of paragraphs 61 to 70, wherein is CH.
Section 74
X 5 71. The compound according to any one of paragraphs 61 to 70, wherein is CF.
Section 75
X 5 is C (CF 3 ), the compound according to any one of Items 61 to 70.
Section 76
X 5 71. The compound according to any one of paragraphs 61 to 70, wherein is C(Cl).
Section 77
X 4 is CR 3 The compound according to any one of Items 61 to 76, which is.
Section 78
X 4 is N, the compound according to any one of paragraphs 61 to 76.
Section 79
X 4 77. The compound according to any one of paragraphs 61 to 76, wherein is CH.
Item 80
X 4 77. The compound according to any one of paragraphs 61 to 76, wherein is CF.
Item 81
X 4 is C (CF 3 ), the compound according to any one of Items 61 to 76.
Section 82
X 4 77. The compound according to any one of paragraphs 61 to 76, wherein is C(Cl).
Section 83
X 6 is CR 3 The compound according to any one of Items 61 to 76, which is.
Section 84
X 6 77. The compound according to any one of paragraphs 61 to 76, wherein is CH.
Section 85
X 6 77. The compound according to any one of paragraphs 61 to 76, wherein is CF.
Item 86
X 6 is C (CF 3 ), the compound according to any one of Items 61 to 76.
Section 87
X 6 77. The compound according to any one of paragraphs 61 to 76, wherein is C(Cl).
Section 88
B 2 but,
The compound according to any one of Items 60 to 87, which is
Section 89
R 5 89. The compound according to paragraph 88, wherein is hydrogen.
Item 90
R 5 89. The compound according to paragraph 88, wherein is methyl.
Item 91
B 2 but,
The compound according to any one of Items 60 to 87, which is
Section 92
B 2 but,
The compound according to any one of Items 60 to 87, which is
Item 93
B 2 but,
The compound according to any one of Items 60 to 87, which is
Section 94
X 11 is a heterocycle, and this 11 Each of the groups is R 3 94. A compound according to any one of paragraphs 60 to 93, optionally substituted with one, two, three or four groups independently selected from.
Section 95
X 11 is a bicyclic ring, and this 11 Each of the groups is R 3 94. A compound according to any one of paragraphs 60 to 93, optionally substituted with one, two, three or four groups independently selected from.
Section 96
X 11 is heteroaryl, aryl or cycloalkyl, and this 11 Each of the groups is R 3 94. A compound according to any one of paragraphs 60 to 93, optionally substituted with one, two, three or four groups independently selected from.
Section 97
X 11 but,
94. The compound according to any one of paragraphs 60 to 93, selected from:
Item 98
X 11 but,
94. The compound according to any one of paragraphs 60 to 93, selected from:
Section 99
X 10 and X 11 together,
94. The compound according to any one of paragraphs 60 to 93, which forms
Item 100
X 10 and X 11 together,
94. The compound according to any one of paragraphs 60 to 93, which forms
Section 101
X 10 is C(R 7 ) 2 99. The compound according to any one of paragraphs 3 to 98, wherein
Item 102
X 10 is CH 2 99. The compound according to any one of paragraphs 3 to 98, which is.
Item 103
X 10 99. The compound according to any one of paragraphs 3 to 98, wherein is C(O).
Section 104
X 10 99. The compound according to any one of paragraphs 3 to 98, wherein is O.
Section 105
X 13 is CR 3 The compound according to any one of Items 3 to 104, which is.
Section 106
X 13 105. The compound according to any one of paragraphs 3 to 104, wherein N is N.
Section 107
X 13 105. The compound according to any one of paragraphs 3 to 104, wherein is CH.
Section 108
X 13 105. The compound according to any one of paragraphs 3 to 104, wherein is CF.
Section 109
X 13 is C (CF 3 ), the compound according to any one of Items 3 to 104.
Item 110
X 13 105. The compound according to any one of paragraphs 3 to 104, wherein is C(Cl).
Item 111
X 14 is CR 3 The compound according to any one of Items 3 to 110, which is.
Item 112
X 14 111. The compound according to any one of paragraphs 3 to 110, wherein N is N.
Item 113
X 14 111. The compound according to any one of paragraphs 3 to 110, wherein is CH.
Section 114
X 14 111. The compound according to any one of paragraphs 3 to 110, wherein is CF.
Section 115
X 14 is C (CF 3 ), the compound according to any one of Items 3 to 110.
Section 116
X 14 111. The compound according to any one of paragraphs 3 to 110, wherein is C(Cl).
Item 117
X 15 is CR 3 The compound according to any one of Items 3 to 116, which is.
Section 118
X 15 is N. The compound according to any one of paragraphs 3 to 116, wherein N is N.
Section 119
X 15 The compound according to any one of paragraphs 3 to 116, wherein is CH.
Section 120
X 15 The compound according to any one of paragraphs 3 to 116, wherein is CF.
Section 121
X 15 is C (CF 3 ), the compound according to any one of Items 3 to 116.
Section 122
X 15 The compound according to any one of paragraphs 3 to 116, wherein is C(Cl).
Section 123
X 16 is CR 3 The compound according to any one of Items 3 to 122, which is.
Section 124
X 16 The compound according to any one of paragraphs 3 to 122, wherein is CH.
Section 125
X 16 123. The compound according to any one of paragraphs 3 to 122, wherein is CF.
Section 126
X 16 is C (CF 3 ). The compound according to any one of Items 3 to 122.
Section 127
X 16 is C(Cl), the compound according to any one of paragraphs 3 to 122.
Section 128
R 8 The compound according to any one of paragraphs 3 to 127, wherein is hydrogen.
Section 129
R 8 The compound according to any one of paragraphs 3 to 127, wherein is methyl.
Section 130
L is the formula:
(In the formula,
X 1 and X 2 is in each case independently a bond, a heterocycle, NR 2 ,C(R 2 ) 2 , O, C(O) and S;
R 2 is in each case independently hydrogen, alkyl, aliphatic, heteroaliphatic, heterocycle, aryl, heteroaryl, -C(O)H, -C(O)OH, -C(O)alkyl, -C(O)O alkyl, -C(O) (aliphatic, aryl, heteroaliphatic or heteroaryl), -C(O)O (aliphatic, aryl, heteroaliphatic or heteroaryl), alkenes and alkynes selected from the group consisting of
R 20 ,R 21 ,R 22 ,R 23 and R 24 is in each case independently a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO 2 -, -S(O)-, -C(S)-, -C(O)NR 2 -, -NR 2 C(O)-, -O-, -S-, -NR 2 -, -C(R 40 R 40 )-,-P(O)(OR 26 )O-, -P(O)(OR 26 )-, alkene, alkyne, haloalkyl, alkoxy, aryl, heterocycle, aliphatic, heteroaliphatic, heteroaryl, lactic acid, glycolic acid, and carbocycle, each of which R 40 optionally substituted with one, two, three or four substituents independently selected from
R 26 are in each case independently selected from the group consisting of hydrogen, alkyl, arylalkyl, heteroarylalkyl, alkene, alkyne, aryl, heteroaryl, heterocycle, aliphatic and heteroaliphatic;
R 40 is in each case independently hydrogen, alkyl, alkene, alkyne, fluoro, bromo, chloro, hydroxyl, alkoxy, azide, amino, cyano, -NH (aliphatic including alkyl), -N (including alkyl) aliphatic) 2 ,-NHSO 2 (aliphatic containing alkyl), -N (aliphatic containing alkyl)SO 2 Alkyl, -NHSO 2 (aryl, heteroaryl or heterocycle), -N(alkyl)SO 2 (aryl, heteroaryl or heterocycle), -NHSO 2 Alkenyl, -N(alkyl)SO 2 alkenyl, -NHSO 2 Alkynyl, -N(alkyl)SO 2 The compound according to any one of paragraphs 3 to 129, which is a linker selected from the group consisting of alkynyl, haloalkyl, aliphatic, heteroaliphatic, aryl, heteroaryl, heterocycle and cycloalkyl.
Section 131
L is the formula:
131. The compound according to paragraph 130, which is a linker for.
Section 132
X 1 132. The compound according to item 130 or 131, wherein is a bond.
Section 133
X 1 132. The compound according to item 130 or 131, wherein is a heterocycle.
Section 134
X 1 is NR 2 The compound according to item 130 or 131, which is
Section 135
X 1 132. The compound according to item 130 or 131, wherein is C(O).
Section 136
X 2 136. The compound according to any one of paragraphs 130 to 135, wherein is a bond.
Section 137
X 2 The compound according to any one of paragraphs 130 to 135, wherein is a heterocycle.
Section 138
X 2 is NR 2 The compound according to any one of Items 130 to 135, which is.
Section 139
X 2 The compound according to any one of paragraphs 130 to 135, wherein is C(O).
Section 140
R 20 139. The compound according to any one of paragraphs 130 to 139, wherein is a bond.
Section 141
R 20 is CH 2 The compound according to any one of Items 130 to 139, which is.
Section 142
R 20 The compound according to any one of paragraphs 130 to 139, wherein is a heterocycle.
Section 143
R 20 A compound according to any one of paragraphs 130 to 139, wherein is aryl.
Section 144
R 20 The compound according to any one of paragraphs 130 to 139, wherein is phenyl.
Section 145
R 20 The compound according to any one of paragraphs 130 to 139, wherein is bicyclic.
Section 146
R 21 The compound according to any one of paragraphs 130 to 145, wherein is a bond.
Section 147
R 21 is CH 2 The compound according to any one of paragraphs 130 to 145, which is.
Section 148
R 21 The compound according to any one of paragraphs 130 to 145, wherein is a heterocycle.
Section 149
R 21 The compound according to any one of paragraphs 130 to 145, wherein is aryl.
Item 150
R 21 The compound according to any one of paragraphs 130 to 145, wherein is phenyl.
Section 151
R 21 The compound according to any one of paragraphs 130 to 145, wherein is bicyclic.
Section 152
L is the formula:
131. The compound according to paragraph 130, which is a linker for.
Section 153
R 22 153. The compound according to any one of paragraphs 130 to 152, wherein is a bond.
Section 154
R 22 is CH 2 The compound according to any one of paragraphs 130 to 152, which is.
Section 155
R 22 The compound according to any one of paragraphs 130 to 152, wherein is a heterocycle.
Section 156
R 22 153. The compound according to any one of paragraphs 130 to 152, wherein is aryl.
Section 157
R 22 The compound according to any one of paragraphs 130 to 152, wherein is phenyl.
Section 158
R 22 The compound according to any one of paragraphs 130 to 152, wherein is bicyclic.
Section 159
L is the formula:
131. The compound according to paragraph 130, which is a linker for.
Item 160
R 23 The compound according to any one of paragraphs 130 to 159, wherein is a bond.
Section 161
R 23 is CH 2 The compound according to any one of paragraphs 130 to 159, which is.
Section 162
R 23 The compound according to any one of paragraphs 130 to 159, wherein is a heterocycle.
Section 163
R 23 A compound according to any one of paragraphs 130 to 159, wherein is aryl.
Section 164
R 23 The compound according to any one of paragraphs 130 to 159, wherein is phenyl.
Section 165
R 23 is bicyclic, the compound according to any one of paragraphs 130 to 159.
Section 166
L is the formula:
131. The compound according to paragraph 130, which is a linker for.
Section 167
R 24 167. The compound according to any one of paragraphs 130 to 166, wherein is a bond.
Section 168
R 24 is CH 2 The compound according to any one of paragraphs 130 to 166, which is.
Section 169
R 24 The compound according to any one of paragraphs 130 to 166, wherein is a heterocycle.
Section 170
R 24 A compound according to any one of paragraphs 130 to 166, wherein is aryl.
Section 171
R 24 The compound according to any one of paragraphs 130 to 166, wherein is phenyl.
Section 172
R 24 is bicyclic, the compound according to any one of paragraphs 130 to 166.
Section 173
R 24 The compound according to any one of paragraphs 130 to 166, wherein is C(O).
Section 174
L is
The compound according to any one of paragraphs 3 to 173, selected from.
Section 175
A compound selected from Table 1 or a pharmaceutically acceptable salt thereof.
Section 176
A compound selected from Table 2 or a pharmaceutically acceptable salt thereof.
Section 177
A pharmaceutical composition comprising a compound according to any one of Items 1 to 176 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
Section 178
mediated by BRD9, optionally comprising administering to a patient in need thereof an effective amount of a compound according to any one of paragraphs 1 to 176, or a pharmaceutically acceptable salt thereof, in a pharmaceutical composition. How to treat the disorder.
Section 179
179. The method of paragraph 178, wherein the patient is a human.
Section 180
A compound according to any one of paragraphs 1 to 176, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutical composition, for use in the treatment of a BRD9-mediated disorder.
Section 181
Use of a compound according to any one of paragraphs 1 to 176, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutical composition, in the treatment of a BRD9-mediated disorder.
Section 182
Use of a compound according to any one of paragraphs 1 to 176, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutical composition, in the manufacture of a medicament for the treatment of a BRD9-mediated disorder.

Claims (69)

Figure 2021178920000001
（式中、
各ａは独立して０、１又は２であり、
各ｙは独立して０、１又は２であり、
Ｘ３、Ｘ４、Ｘ５及びＸ６はＮ、ＣＨ及びＣＲ３からなる群から選択され、ここでＸ３、Ｘ４、Ｘ５及びＸ６の３つ以下がＮであり、
Ｘ７はＮ又はＣＨであり、
Ｘ８及びＸ９は、いずれの場合にも各々独立してＮ及びＣＨからなる群から選択され、ここでＸ８又はＸ９の少なくとも１つがＣＨであり、
Ｘ１７はアリール、ヘテロアリール、二環又はシクロアルキルであり、その各々がＲ３から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換され、
Ｑ１は、いずれの場合にも独立してＮＨ、Ｎ（アルキル）、Ｎ（ハロアルキル）、ＣＨ２、Ｏ及びＳからなる群から選択され、ここでＸ７がＮである場合、Ｑ１はＣＨ２であり、
Ｒは、いずれの場合にも独立して水素、Ｃ１～Ｃ４ハロアルキル、Ｃ１～Ｃ４アルキル、フッ素、塩素、臭素、ＣＨ２Ｆ、ＣＨＦ２、ＣＦ３、ＣＨ２Ｃｌ、ＣＨＣｌ２、ＣＣｌ３、ＣＨ２Ｂｒ、ＣＨＢｒ２及びＣＢｒ３からなる群から選択され、
Ｒ３は、いずれの場合にも独立して水素、ヒドロキシル、アルコキシ、Ｃ１～Ｃ４アルキル、Ｃ１～Ｃ４ハロアルキル、シクロアルキル、フッ素、塩素、及び臭素からなる群から選択され、
ＢはＢ１及びＢ２から選択され、
Ｂ１は、
Figure 2021178920000002
からなる群から選択され、
Ｂ２は、
Figure 2021178920000003
からなる群から選択され、
Ｘ１０はＣ（Ｒ７）２、Ｃ（Ｏ）若しくはＯであり、
Ｘ１１は複素環、ヘテロアリール、アリール、シクロアルキル若しくは二環であり、このＸ１１基の各々がＲ３から独立して選択される１つ、２つ、３つ若しくは４つの基で任意に置換されるか、
又はＸ１０及びＸ１１が一緒に、
Figure 2021178920000004
を形成し、
Ｘ１３、Ｘ１４、Ｘ１５及びＸ１６は独立してＮ、ＣＨ及びＣＲ４からなる群から選択され、ここでＸ１３、Ｘ１４、Ｘ１５及びＸ１６の３つ以下がＮであり、
各Ｒ４は独立して水素、アリール、ヘテロアリール、Ｃ１～Ｃ４アルコキシ、Ｃ１～Ｃ４ハロアルキル、Ｃ１～Ｃ４ハロアルコキシ、Ｃ１～Ｃ４アルキル、フッ素、塩素、臭素及びヨウ素から選択され、
ここで、隣接した炭素原子上の２つのＲ４基が任意に結合して縮合環を形成してもよく、該縮合環は１つ、２つ又は３つのＲ置換基で任意に置換され、
Ｒ５は水素、Ｃ１～Ｃ４アルキル、アリル、クロチル、アルケニル、アルキニル、ハロアルキル又はシクロアルキルであり、
各Ｒ６は独立して水素、Ｃ１～Ｃ４アルコキシ、Ｃ１～Ｃ４アルキル、Ｃ１～Ｃ４ハロアルキル、フッ素、塩素、臭素及びヨウ素から選択され、
各Ｒ７は独立して水素又はＣ１～Ｃ４アルキルであり、
Ｒ８は水素、Ｃ１～Ｃ４アルキル、アリル、クロチル、アルケニル、アルキニル、ハロアルキル又はシクロアルキルであり、
Ｌが式：
Figure 2021178920000005
（式中、
Ｘ１及びＸ２は、いずれの場合にも独立して結合、複素環、ＮＲ２、Ｃ（Ｒ２）２、Ｏ、Ｃ（Ｏ）及びＳから選択され、
Ｒ２は、いずれの場合にも独立して水素、アルキル、複素環、アリール、ヘテロアリール、－Ｃ（Ｏ）Ｈ、－Ｃ（Ｏ）ＯＨ、－Ｃ（Ｏ）アルキル、－Ｃ（Ｏ）Ｏアルキル、－Ｃ（Ｏ）（アリール又はヘテロアリール）、－Ｃ（Ｏ）Ｏ（アリール又はヘテロアリール）、アルケン及びアルキンからなる群から選択され、
Ｒ２０、Ｒ２１、Ｒ２２、Ｒ２３及びＲ２４は、いずれの場合にも独立して結合、アルキル、－Ｃ（Ｏ）－、－Ｃ（Ｏ）Ｏ－、－ＯＣ（Ｏ）－、－ＳＯ２－、－Ｓ（Ｏ）－、－Ｃ（Ｓ）－、－Ｃ（Ｏ）ＮＲ２－、－ＮＲ２Ｃ（Ｏ）－、－Ｏ－、－Ｓ－、－ＮＲ２－、－Ｃ（Ｒ４０Ｒ４０）－、二環、アルケン、アルキン、ハロアルキル、アルコキシ、アリール、複素環、ヘテロアリール、乳酸、グリコール酸及び炭素環からなる群から選択され、その各々がＲ４０から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換され、
Ｒ４０は、いずれの場合にも独立して水素、アルキル、アルケン、アルキン、フルオロ、ブロモ、クロロ、ヒドロキシル、アルコキシ、アジド、アミノ、シアノ、－ＮＨ（アルキル）、－Ｎ（アルキル）２、－ＮＨＳＯ２（アルキル）、－Ｎ（アルキル）ＳＯ２アルキル、－ＮＨＳＯ２（アリール、ヘテロアリール又は複素環）、－Ｎ（アルキル）ＳＯ２（アリール、ヘテロアリール又は複素環）、－ＮＨＳＯ２アルケニル、－Ｎ（アルキル）ＳＯ２アルケニル、－ＮＨＳＯ２アルキニル、－Ｎ（アルキル）ＳＯ２アルキニル、ハロアルキル、アリール、ヘテロアリール、複素環及びシクロアルキルからなる群から選択される）の二価連結基である）からなる群から選択される化合物又はその薬学的に許容可能な塩。
Figure 2021178920000001
(In the formula,
each a is independently 0, 1 or 2,
each y is independently 0, 1 or 2;
X3 , X4 , X5 and X6 are selected from the group consisting of N, CH and CR3 , where no more than three of X3 , X4 , X5 and X6 are N;
X 7 is N or CH,
X 8 and X 9 are in each case each independently selected from the group consisting of N and CH, where at least one of X 8 or X 9 is CH;
X 17 is aryl, heteroaryl, bicyclic or cycloalkyl, each optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 3 ;
Q 1 is in each case independently selected from the group consisting of NH, N(alkyl), N(haloalkyl), CH 2 , O and S, where if X 7 is N, Q 1 is CH 2 ,
R is in each case independently hydrogen, C 1 -C 4 haloalkyl, C 1 -C 4 alkyl, fluorine, chlorine, bromine, CH 2 F, CHF 2 , CF 3 , CH 2 Cl, CHCl 2 , selected from the group consisting of CCl3 , CH2Br , CHBr2 and CBr3 ;
R 3 is in each case independently selected from the group consisting of hydrogen, hydroxyl, alkoxy, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, cycloalkyl, fluorine, chlorine, and bromine;
B is selected from B 1 and B 2 ;
B1 is
Figure 2021178920000002
selected from the group consisting of
B2 is
Figure 2021178920000003
selected from the group consisting of
X 10 is C(R 7 ) 2 , C(O) or O,
X 11 is a heterocycle, heteroaryl, aryl, cycloalkyl or bicyclic, and each of the X 11 groups is optionally one, two, three or four groups independently selected from R 3 . replaced or
or X 10 and X 11 together,
Figure 2021178920000004
form,
X13 , X14 , X15 and X16 are independently selected from the group consisting of N, CH and CR4 , where no more than three of X13 , X14 , X15 and X16 are N;
Each R 4 is independently hydrogen, aryl, heteroaryl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl , C 1 -C 4 haloalkoxy, C 1 -C 4 alkyl, fluorine, chlorine, bromine and iodine selected from
wherein two R groups on adjacent carbon atoms may optionally be combined to form a fused ring, which fused ring is optionally substituted with one, two or three R substituents,
R 5 is hydrogen, C 1 -C 4 alkyl, allyl, crotyl, alkenyl, alkynyl, haloalkyl or cycloalkyl;
each R 6 is independently selected from hydrogen, C 1 -C 4 alkoxy, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, fluorine, chlorine, bromine and iodine;
each R 7 is independently hydrogen or C 1 -C 4 alkyl;
R 8 is hydrogen, C 1 -C 4 alkyl, allyl, crotyl, alkenyl, alkynyl, haloalkyl or cycloalkyl;
L is the formula:
Figure 2021178920000005
(In the formula,
X 1 and X 2 are in each case independently selected from a bond, heterocycle, NR 2 , C(R 2 ) 2 , O, C(O) and S;
R 2 in each case is independently hydrogen, alkyl, heterocycle, aryl, heteroaryl, -C(O)H, -C(O)OH, -C(O)alkyl, -C(O) selected from the group consisting of O alkyl, -C(O) (aryl or heteroaryl), -C(O)O (aryl or heteroaryl), alkenes and alkynes;
R 20 , R 21 , R 22 , R 23 and R 24 each independently represent a bond, alkyl, -C(O)-, -C(O)O-, -OC(O)-, -SO 2 -, -S(O)-, -C(S)-, -C(O)NR 2 -, -NR 2 C(O)-, -O-, -S-, -NR 2 -, -C(R 40 R 40 )-, bicyclic, alkene, alkyne, haloalkyl, alkoxy, aryl, heterocycle, heteroaryl, lactic acid, glycolic acid and carbocycle, each of which is independent of R 40 optionally substituted with 1, 2, 3 or 4 substituents selected from
In each case, R 40 is independently hydrogen, alkyl, alkene, alkyne, fluoro, bromo, chloro, hydroxyl, alkoxy, azide, amino, cyano, -NH(alkyl), -N(alkyl) 2 , - NHSO 2 (alkyl), -N(alkyl)SO 2alkyl , -NHSO 2 (aryl, heteroaryl or heterocycle), -N(alkyl)SO 2 (aryl, heteroaryl or heterocycle), -NHSO 2alkenyl , -N(alkyl) SO2alkenyl , -NHSO2alkynyl , -N(alkyl) SO2alkynyl , haloalkyl, aryl, heteroaryl, heterocycle and cycloalkyl). ) or a pharmaceutically acceptable salt thereof. 式：
Figure 2021178920000006
の化合物又はその薬学的に許容可能な塩である、請求項１に記載の化合物。 formula:
Figure 2021178920000006
2. The compound according to claim 1, which is a compound of or a pharmaceutically acceptable salt thereof. Ｘ８がＮであり、Ｘ９がＣＨであり、又はＸ８がＣＨであり、Ｘ９がＮである、請求項２に記載の化合物。 3. A compound according to claim 2, wherein X8 is N and X9 is CH, or X8 is CH and X9 is N. Ｘ８がＣＨであり、Ｘ９がＣＨである、請求項２に記載の化合物。 3. A compound according to claim 2, wherein X8 is CH and X9 is CH.
Figure 2021178920000007
が、
Figure 2021178920000008
である、請求項２～４のいずれか一項に記載の化合物。
Figure 2021178920000007
but,
Figure 2021178920000008
The compound according to any one of claims 2 to 4, which is ＲがＣ１～Ｃ４ハロアルキル、Ｃ１～Ｃ４アルキル、フッ素、塩素又は臭素である、請求項１～５のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 5, wherein R is C 1 -C 4 haloalkyl, C 1 -C 4 alkyl, fluorine, chlorine or bromine. Ｒがフッ素である、請求項１～５のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 5, wherein R is fluorine. 式：
Figure 2021178920000009
の化合物又はその薬学的に許容可能な塩である、請求項１に記載の化合物。 formula:
Figure 2021178920000009
2. The compound according to claim 1, which is a compound of or a pharmaceutically acceptable salt thereof. Ｘ１７がＲ３から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換されるアリール基である、請求項８に記載の化合物。 9. A compound according to claim 8, wherein X17 is an aryl group optionally substituted with 1, 2, 3 or 4 substituents independently selected from R3 . Ｘ１７がフェニルである、請求項９に記載の化合物。 10. A compound according to claim 9, wherein X17 is phenyl. Ｘ１７がヘテロアリール基又はシクロアルキル基であり、その各々がＲ３から独立して選択される１つ、２つ、３つ又は４つの置換基で任意に置換される、請求項８に記載の化合物。 9. X 17 is a heteroaryl group or a cycloalkyl group, each of which is optionally substituted with 1, 2, 3 or 4 substituents independently selected from R 3 compound. Ｂが、
Figure 2021178920000010
である、請求項１～１１のいずれか一項に記載の化合物。 B is
Figure 2021178920000010
The compound according to any one of claims 1 to 11, which is 式：
Figure 2021178920000011
の化合物又はその薬学的に許容可能な塩である、請求項１に記載の化合物。 formula:
Figure 2021178920000011
The compound according to claim 1, which is a compound of or a pharmaceutically acceptable salt thereof. Ｑ１がＮＨであり、Ｘ７がＣＨである、請求項１～１３のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 13, wherein Q 1 is NH and X 7 is CH. Ｘ３がＣＲ３である、請求項１～１４のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 14, wherein X 3 is CR 3 . Ｘ３がＣＨ又はＣＦである、請求項１～１４のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 14, wherein X 3 is CH or CF. Ｘ５がＣＲ３である、請求項１～１６のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 16, wherein X 5 is CR 3 . Ｘ５がＣＨ又はＣＦである、請求項１～１６のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 16, wherein X 5 is CH or CF. Ｘ４がＣＲ３である、請求項１～１８のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 18, wherein X 4 is CR 3 . Ｘ４がＣＦである、請求項１～１８のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 18, wherein X 4 is CF. Ｘ６がＣＲ３である、請求項１～２０のいずれか一項に記載の化合物。 21. A compound according to any one of claims 1 to 20, wherein X 6 is CR 3 . Ｘ６がＣＨ又はＣＦである、請求項１～２０のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 20, wherein X 6 is CH or CF. Ｂ２が、
Figure 2021178920000012
である、請求項１３～２２のいずれか一項に記載の化合物。 B 2 is
Figure 2021178920000012
A compound according to any one of claims 13 to 22, which is Ｘ１１が、Ｒ３から独立して選択される１つ、２つ、３つ又は４つの基で任意に置換される複素環である、請求項１３～２３のいずれか一項に記載の化合物。 A compound according to any one of claims 13 to 23, wherein X 11 is a heterocycle optionally substituted with 1, 2, 3 or 4 groups independently selected from R 3 . Ｘ１１が、Ｒ３から独立して選択される１つ、２つ、３つ又は４つの基で任意に置換される二環である、請求項１３～２３のいずれか一項に記載の化合物。 A compound according to any one of claims 13 to 23, wherein X 11 is a bicyclic ring optionally substituted with 1, 2, 3 or 4 groups independently selected from R 3 . Ｘ１１が、
Figure 2021178920000013
及び
から選択される、請求項１３～２３のいずれか一項に記載の化合物。 X 11 is
Figure 2021178920000013
A compound according to any one of claims 13 to 23, selected from and. Ｘ１０がＣＨ２である、請求項１～２６のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 26, wherein X 10 is CH 2 . Ｘ１３がＣＲ４である、請求項１～２７のいずれか一項に記載の化合物。 28. A compound according to any one of claims 1 to 27, wherein X 13 is CR 4 . Ｘ１４がＣＨである、請求項１～２８のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 28, wherein X 14 is CH. Ｘ１５がＣＨである、請求項１～２９のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 29, wherein X 15 is CH. Ｘ１６がＣＲ４である、請求項１～３０のいずれか一項に記載の化合物。 31. A compound according to any one of claims 1 to 30, wherein X 16 is CR 4 . Ｘ１６がＣＨである、請求項１～３１のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 31, wherein X 16 is CH. Ｘ１６がＣＦである、請求項１～３１のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 31, wherein X 16 is CF. Ｒ８がメチルである、請求項１～３３のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 33, wherein R 8 is methyl. Ｘ１が結合又は複素環である、請求項１～３４のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 34, wherein X 1 is a bond or a heterocycle. Ｘ２が結合又は複素環である、請求項１～３５のいずれか一項に記載の化合物。 36. A compound according to any one of claims 1 to 35, wherein X 2 is a bond or a heterocycle. Ｒ２０が結合、ＣＨ２、複素環、アリール又は二環である、請求項１～３６のいずれか一項に記載の化合物。 37. A compound according to any one of claims 1 to 36, wherein R 20 is a bond, CH 2 , heterocycle, aryl or bicyclic. Ｒ２０がフェニルである、請求項１～３６のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 36, wherein R 20 is phenyl. Ｒ２１が結合、ＣＨ２、複素環、アリール又は二環である、請求項１～３８のいずれか一項に記載の化合物。 39. A compound according to any one of claims 1 to 38, wherein R 21 is a bond, CH 2 , heterocycle, aryl or bicyclic. Ｒ２１がフェニルである、請求項１～３８のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 38, wherein R 21 is phenyl. Ｒ２２が結合、ＣＨ２、複素環、アリール又は二環である、請求項１～４０のいずれか一項に記載の化合物。 41. A compound according to any one of claims 1 to 40, wherein R 22 is a bond, CH 2 , heterocycle, aryl or bicyclic. Ｒ２２がフェニルである、請求項１～４０のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 40, wherein R 22 is phenyl. Ｒ２３が結合、ＣＨ２、複素環、アリール又は二環である、請求項１～４２のいずれか一項に記載の化合物。 43. A compound according to any one of claims 1 to 42, wherein R 23 is a bond, CH 2 , heterocycle, aryl or bicyclic. Ｒ２３がフェニルである、請求項１～４２のいずれか一項に記載の化合物。 A compound according to any one of claims 1 to 42, wherein R 23 is phenyl. Ｒ２４が結合、ＣＨ２、複素環、アリール又は二環である、請求項１～４４のいずれか一項に記載の化合物。 45. A compound according to any one of claims 1 to 44, wherein R 24 is a bond, CH 2 , heterocycle, aryl or bicyclic. Ｒ２４がフェニルである、請求項１～４４のいずれか一項に記載の化合物。 45. A compound according to any one of claims 1 to 44, wherein R 24 is phenyl. Ｌが、
Figure 2021178920000014
から選択される、請求項１～４６のいずれか一項に記載の化合物。 L is
Figure 2021178920000014
47. A compound according to any one of claims 1 to 46, selected from: 明細書の表１の化合物番号１～２４５から選択される化合物又はその薬学的に許容可能な塩。 A compound selected from compound numbers 1 to 245 in Table 1 of the specification or a pharmaceutically acceptable salt thereof. 明細書の表２の化合物番号２４６～２７５から選択される化合物又はその薬学的に許容可能な塩。 A compound selected from compound numbers 246 to 275 in Table 2 of the specification or a pharmaceutically acceptable salt thereof. 式：
Figure 2021178920000015
（式中、
Ｘ３はＣＨ、Ｎ及びＣＲ３からなる群から選択され、
Ｑ１はＮＨ、Ｎ（アルキル）又はＯであり、
Ｒ３は、いずれの場合にも独立してフッ素、水素、Ｃ１～Ｃ４アルキル、Ｃ１～Ｃ４ハロアルキル、塩素及び臭素からなる群から選択され、
Ｘ１０はＣ（Ｒ７）２、Ｃ（Ｏ）又はＯであり、
Ｘ１１は、Ｒ３から独立して選択される１つ、２つ、３つ又は４つの基で任意に置換される複素環であり、
Ｘ１６はＣＲ４、Ｎ及びＣＨからなる群から選択され、
各Ｒ４は独立して水素、Ｃ１～Ｃ４アルコキシ、Ｃ１～Ｃ４ハロアルキル、Ｃ１～Ｃ４ハロアルコキシ、Ｃ１～Ｃ４アルキル、フッ素、塩素及び臭素から選択され、
各Ｒ７は独立して水素又はＣ１～Ｃ４アルキルであり、
Ｒ８は水素、Ｃ１～Ｃ４アルキル、アリル、クロチル、アルケニル、アルキニル、ハロアルキル又はシクロアルキルである）の化合物又はその薬学的に許容可能な塩である、請求項１に記載の化合物。 formula:
Figure 2021178920000015
(In the formula,
X 3 is selected from the group consisting of CH, N and CR 3 ;
Q 1 is NH, N (alkyl) or O,
R 3 is in each case independently selected from the group consisting of fluorine, hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, chlorine and bromine;
X 10 is C(R 7 ) 2 , C(O) or O,
X 11 is a heterocycle optionally substituted with 1, 2, 3 or 4 groups independently selected from R 3 ,
X 16 is selected from the group consisting of CR 4 , N and CH;
each R 4 is independently selected from hydrogen, C 1 -C 4 alkoxy, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 alkyl, fluorine, chlorine and bromine;
each R 7 is independently hydrogen or C 1 -C 4 alkyl;
2. The compound according to claim 1, wherein R 8 is hydrogen, C 1 -C 4 alkyl, allyl, crotyl, alkenyl, alkynyl, haloalkyl or cycloalkyl, or a pharmaceutically acceptable salt thereof. 式：
Figure 2021178920000016
若しくは
の化合物又はその薬学的に許容可能な塩である、請求項５０に記載の化合物。 formula:
Figure 2021178920000016
51. The compound according to claim 50, which is a compound of or a pharmaceutically acceptable salt thereof. Ｑ１がＮＨである、請求項５０又は５１に記載の化合物。 52. A compound according to claim 50 or 51, wherein Q1 is NH. 式：
Figure 2021178920000017
の化合物又はその薬学的に許容可能な塩である、請求項５０～５２のいずれか一項に記載の化合物。 formula:
Figure 2021178920000017
or a pharmaceutically acceptable salt thereof. Ｒ７がＣＨ３である、請求項５０～５３のいずれか一項に記載の化合物。 54. A compound according to any one of claims 50 to 53, wherein R 7 is CH 3 . Ｒ４がＣＨ３又はＣ１～Ｃ４アルコキシである、請求項５０に記載の化合物。 51. A compound according to claim 50, wherein R 4 is CH 3 or C 1 -C 4 alkoxy. 式：
Figure 2021178920000018
の化合物又はその薬学的に許容可能な塩である、請求項５０～５２及び５５のいずれか一項に記載の化合物。 formula:
Figure 2021178920000018
or a pharmaceutically acceptable salt thereof. Ｘ１１が、
Figure 2021178920000019
及び
から選択される、請求項５０～５６のいずれか一項に記載の化合物。 X 11 is
Figure 2021178920000019
57. A compound according to any one of claims 50 to 56, selected from and. 式：
Figure 2021178920000020
の化合物又はその薬学的に許容可能な塩である、請求項５０～５２並びに５５及び５６のいずれか一項に記載の化合物。 formula:
Figure 2021178920000020
or a pharmaceutically acceptable salt thereof, according to any one of claims 50 to 52 and 55 and 56. Ｘ１０がＣＨ２である、請求項５０～５２及び５４～５８のいずれか一項に記載の化合物。 A compound according to any one of claims 50-52 and 54-58, wherein X 10 is CH 2 .
Figure 2021178920000021
及び
又はその薬学的に許容可能な塩からなる群から選択される、請求項５０に記載の化合物。
Figure 2021178920000021
51. A compound according to claim 50, selected from the group consisting of: and or a pharmaceutically acceptable salt thereof. 構造：
Figure 2021178920000022
の化合物又はその薬学的に許容可能な塩である、請求項５０に記載の化合物。 structure:
Figure 2021178920000022
51. The compound according to claim 50, which is a compound of or a pharmaceutically acceptable salt thereof. 構造：
Figure 2021178920000023
の化合物又はその薬学的に許容可能な塩である、請求項５０に記載の化合物。 structure:
Figure 2021178920000023
51. The compound according to claim 50, which is a compound of or a pharmaceutically acceptable salt thereof. 構造：
Figure 2021178920000024
の化合物又はその薬学的に許容可能な塩である、請求項５０に記載の化合物。 structure:
Figure 2021178920000024
51. The compound according to claim 50, which is a compound of or a pharmaceutically acceptable salt thereof. 構造：
Figure 2021178920000025
の化合物又はその薬学的に許容可能な塩である、請求項５０に記載の化合物。 structure:
Figure 2021178920000025
51. The compound according to claim 50, which is a compound of or a pharmaceutically acceptable salt thereof. 構造：
Figure 2021178920000026
の化合物又はその薬学的に許容可能な塩である、請求項５０に記載の化合物。 structure:
Figure 2021178920000026
51. The compound according to claim 50, which is a compound of or a pharmaceutically acceptable salt thereof. 請求項１～６５のいずれか一項に記載の化合物又はその薬学的に許容可能な塩と、薬学的に許容可能な賦形剤とを含む、ヒト患者におけるＢＲＤ９媒介性障害の治療のための医薬組成物。 A compound according to any one of claims 1 to 65, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient for the treatment of BRD9-mediated disorders in a human patient. Pharmaceutical composition. 前記ＢＲＤ９媒介性障害が滑膜肉腫である、請求項６６に記載の医薬組成物。 67. The pharmaceutical composition of claim 66, wherein the BRD9-mediated disorder is synovial sarcoma. 前記ＢＲＤ９媒介性障害が多発性骨髄腫である、請求項６６に記載の医薬組成物。 67. The pharmaceutical composition of claim 66, wherein said BRD9-mediated disorder is multiple myeloma. 前記ＢＲＤ９媒介性障害がＳＭＡＲＣＢ１撹乱癌である、請求項６６に記載の医薬組成物。 67. The pharmaceutical composition of claim 66, wherein the BRD9-mediated disorder is a SMARCB1-disrupted cancer.
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