JP2018532706A - Tyk2阻害剤およびその使用 - Google Patents
Tyk2阻害剤およびその使用 Download PDFInfo
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- JP2018532706A JP2018532706A JP2018512319A JP2018512319A JP2018532706A JP 2018532706 A JP2018532706 A JP 2018532706A JP 2018512319 A JP2018512319 A JP 2018512319A JP 2018512319 A JP2018512319 A JP 2018512319A JP 2018532706 A JP2018532706 A JP 2018532706A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
Abstract
Description
本発明は、非レセプターチロシン−プロテインキナーゼ2(「TYK2」)(チロシンキナーゼ2としても公知)を阻害するために有用な化合物および方法に関する。本発明はまた、本発明の化合物を含有する薬学的に受容可能な組成物、および種々の障害の処置においてこれらの組成物を使用する方法を提供する。
新たな治療剤の探索は、近年、疾患に関連する酵素または他の生体分子の構造のよりよい理解によって、大いに助けられている。広範な研究の主題である酵素の1つの重要なクラスは、プロテインキナーゼファミリーである。
本発明の化合物およびその薬学的に受容可能な組成物は、TYK2キナーゼの阻害剤として有効であることが、ここで見出された。このような化合物は、一般式I:
1.本発明の特定の実施形態の一般的な説明:
本発明の化合物およびその組成物は、TYK2プロテインキナーゼの阻害剤として有用である。
XおよびYの各々は独立して、=C(R6)−または=N−であり;
環Aは、フェニル;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員の部分不飽和単環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する6員〜12員の部分不飽和二環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員の単環式ヘテロアリール環;または窒素、酸素、および硫黄から独立して選択される2個〜4個のヘテロ原子を有する7員〜12員の二環式ヘテロアリール環であり;
R1およびR1’の各々は独立して、水素、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであるか;あるいは
R1とR1’とは、これらの介在する原子と一緒になって、窒素、酸素、および硫黄から独立して選択される0個〜2個のヘテロ原子を有する、必要に応じて置換された3員〜7員のスピロ縮合環を形成し;
各R2は独立して、C1〜6脂肪族、フェニル、窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する4員〜7員の飽和または部分不飽和の複素環式環、ならびに窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環からなる群より選択される、必要に応じて置換された基であり;
R3は、C2〜6脂肪族またはCy1であり;ここでR3は、n個の例のR8で置換されており;
R5は、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、−N(R)S(O)2R、およびCy2であり;ここでR5は、p個の例のR9で置換されているか;または
環Aが二環式もしくは部分不飽和である場合、L1R5は一緒になって、存在しないことも可能であり;
Cy1およびCy2の各々は独立して、フェニル;3員〜7員の飽和もしくは部分不飽和の単環式炭素環;6員〜12員の二環式炭素環式環;窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する3員〜7員の飽和もしくは部分不飽和の単環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜3個のヘテロ原子を有する6員〜12員の飽和もしくは部分不飽和の二環式複素環式環;または窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環であり;
R6の各例は独立して、水素、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
R7およびR8の各例は独立して、オキソ、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
R9の各例は独立して、オキソ、C1〜6ヒドロキシ脂肪族、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
L1は、共有結合、またはC1〜6の二価の飽和もしくは不飽和の、直鎖もしくは分枝鎖の炭化水素鎖であり、ここでこの鎖の1個もしくは2個のメチレン単位は、必要に応じて独立して、−N(R)−、−N(R)C(O)−、−C(O)N(R)−、−N(R)S(O)2−、−S(O)2N(R)−、−O−、−C(O)−、−OC(O)−、−C(O)O−、−S−、−S(O)−もしくは−S(O)2−によって置き換えられており;
mは、0〜2であり;
nは、0〜4であり;
pは、0〜3であり;そして
各Rは独立して、水素であるか、またはC1〜6脂肪族、フェニル、窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する4員〜7員の飽和もしくは部分不飽和の複素環式、ならびに窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環から選択される必要に応じて置換された基であるか、あるいは
同じ窒素上の2個のR基は、これらの介在する原子と一緒になって、この窒素に加えて、窒素、酸素、および硫黄から独立して選択される0個〜3個のヘテロ原子を有する4員〜7員の飽和、部分不飽和、もしくはヘテロアリールの環を形成する。
2.化合物および定義:
3.例示的な実施形態の説明:
上記のように、特定の実施形態において、本発明は、式I:
XおよびYの各々は独立して、=C(R6)−または=N−であり;
環Aは、フェニル;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員の部分不飽和単環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する6員〜12員の部分不飽和二環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員の単環式ヘテロアリール環;または窒素、酸素、および硫黄から独立して選択される2個〜4個のヘテロ原子を有する7員〜12員の二環式ヘテロアリール環であり;
R1およびR1’の各々は独立して、水素、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであるか;あるいは
R1とR1’とは、これらの介在する原子と一緒になって、窒素、酸素、および硫黄から独立して選択される0個〜2個のヘテロ原子を有する、必要に応じて置換された3員〜7員のスピロ縮合環を形成し;
各R2は独立して、C1〜6脂肪族、フェニル、窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する4員〜7員の飽和または部分不飽和の複素環式環、ならびに窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環からなる群より選択される、必要に応じて置換された基であり;
R3は、C2〜6脂肪族またはCy1であり;ここでR3は、n個の例のR8で置換されており;
R5は、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、−N(R)S(O)2R、およびCy2であり;ここでR5は、p個の例のR9で置換されているか;あるいは
環Aが二環式もしくは部分不飽和である場合、L1R5は一緒になって、存在しないことも可能であり;
Cy1およびCy2の各々は独立して、フェニル;3員〜7員の飽和もしくは部分不飽和の単環式炭素環;6員〜12員の二環式炭素環式環;窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する3員〜7員の飽和もしくは部分不飽和の単環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜3個のヘテロ原子を有する6員〜12員の飽和もしくは部分不飽和の二環式複素環式環;または窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環であり;
R6の各例は独立して、水素、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
R7およびR8の各例は独立して、オキソ、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
R9の各例は独立して、オキソ、C1〜6ヒドロキシ脂肪族、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
L1は、共有結合、またはC1〜6の二価の飽和もしくは不飽和の、直鎖もしくは分枝鎖の炭化水素鎖であり、ここでこの鎖の1個もしくは2個のメチレン単位は、必要に応じて独立して、−N(R)−、−N(R)C(O)−、−C(O)N(R)−、−N(R)S(O)2−、−S(O)2N(R)−、−O−、−C(O)−、−OC(O)−、−C(O)O−、−S−、−S(O)−もしくは−S(O)2−によって置き換えられており;
mは、0〜2であり;
nは、0〜4であり;
pは、0〜3であり;そして
各Rは独立して、水素であるか、またはC1〜6脂肪族、フェニル、窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する4員〜7員の飽和もしくは部分不飽和の複素環式、ならびに窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環から選択される必要に応じて置換された基であるか、あるいは
同じ窒素上の2個のR基は、これらの介在する原子と一緒になって、この窒素に加えて、窒素、酸素、および硫黄から独立して選択される0個〜3個のヘテロ原子を有する4員〜7員の飽和、部分不飽和、もしくはヘテロアリールの環を形成する。
5.使用、処方および投与
薬学的に受容可能な組成物
化合物および薬学的に受容可能な組成物の使用
併用療法
以下の実施例に記載されるように、特定の例示的実施形態において、化合物は、以下の一般手順に従って調製される。本発明の化合物の合成を記載するが、以下の一般方法および当業者に公知である他の方法が、全ての化合物、ならびに本明細書中に記載されるようなこれらの化合物の各々のサブクラスおよび種に適用され得ることが、理解される。
実施例75。3−フルオロ−2−(5−オキソ−4−(4,5,6,7−テトラヒドロ−2H−ピラゾロ[3,4−b]ピリジン−2−イル)−6,7−ジヒドロ−5H−ピロロ[3,4−b]ピリジン−2−イル)ベンゾニトリル,I−75の合成
実施例151。3−フルオロ−2−(4−(3−イソプロピル−1H−ピラゾール−1−イル)−5−オキソ−6,7−ジヒドロ−5H−ピロロ[3,4−b]ピリジン−2−イル)ベンゾニトリル,I−151の合成
実施例152。3−フルオロ−2−(5−オキソ−4−(3−(3−(ピロリジン−1−カルボニル)ピペリジン−1−イル)−1H−ピラゾール−1−イル)−6,7−ジヒドロ−5H−ピロロ[3,4−b]ピリジン−2−イル)ベンゾニトリル,I−152の合成
実施例178。2−(4−(3−((3R,4S)−3,4−ジヒドロキシアゼパン−1−イル)−1H−ピラゾール−1−イル)−5−オキソ−6,7−ジヒドロ−5H−ピロロ[3,4−b]ピリジン−2−イル)−3−フルオロベンゾニトリル,I−178の合成
実施例198。(R)−3−フルオロ−2−(4−(3−(3−ヒドロキシ−3−(ピロリジン−1−カルボニル)−ピロリジン−1−イル)−1H−ピラゾール−1−イル)−5−オキソ−6,7−ジヒドロ−5H−ピロロ[3,4−b]ピリジン−2−イル)ベンゾニトリル,I−198の合成
実施例199。3−フルオロ−2−(4−(3−((3R,4S)−3−ヒドロキシ−4−(メトキシ−d3)ピロリジン−1−イル)−1H−ピラゾール−1−イル)−5−オキソ−6,7−ジヒドロ−5H−ピロロ[3,4−b]ピリジン−2−イル)ベンゾニトリル,I−199の合成
実施例216。(3R,4R)−1−(1−(2−(2−シアノ−6−フルオロフェニル)−5−オキソ−6,7−ジヒドロ−5H−ピロロ[3,4−b]ピリジン−4−イル)−1H−ピラゾール−3−イル)−3−ヒドロキシピペリジン−4−カルボニトリル,I−216の合成
実施例228。3−フルオロ−2−(4−(3−((3S,4R)−3−ヒドロキシ−4−メトキシ−3−メチルピペリジン−1−イル)−1H−ピラゾール−1−イル)−5−オキソ−6,7−ジヒドロ−5H−ピロロ[3,4−b]ピリジン−2−イル)ベンゾニトリルI−228の合成
Claims (41)
- 式I:
XおよびYの各々は独立して、=C(R6)−または=N−であり;
環Aは、フェニル;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員の部分不飽和単環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する6員〜12員の部分不飽和二環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員の単環式ヘテロアリール環;または窒素、酸素、および硫黄から独立して選択される2個〜4個のヘテロ原子を有する7員〜12員の二環式ヘテロアリール環であり;
R1およびR1’の各々は独立して、水素、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであるか;あるいは
R1とR1’とは、これらの介在する原子と一緒になって、窒素、酸素、および硫黄から独立して選択される0個〜2個のヘテロ原子を有する、必要に応じて置換された3員〜7員のスピロ縮合環を形成し;
各R2は独立して、C1〜6脂肪族、フェニル、窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する4員〜7員の飽和または部分不飽和の複素環式環、ならびに窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環からなる群より選択される、必要に応じて置換された基であり;
R3は、C2〜6脂肪族またはCy1であり;ここでR3は、n個の例のR8で置換されており;
R5は、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、−N(R)S(O)2R、およびCy2であり;ここでR5は、p個の例のR9で置換されているか;または
環Aが部分不飽和である場合、L1R5は一緒になって、存在しないことも可能であり;
Cy1およびCy2の各々は独立して、フェニル;3員〜7員の飽和もしくは部分不飽和の単環式炭素環;6員〜12員の二環式炭素環式環;窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する3員〜7員の飽和もしくは部分不飽和の単環式複素環式環;窒素、酸素、および硫黄から独立して選択される1個〜3個のヘテロ原子を有する6員〜12員の飽和もしくは部分不飽和の二環式複素環式環;または窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環であり;
R6の各例は独立して、水素、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
R7およびR8の各例は独立して、オキソ、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
R9の各例は独立して、オキソ、C1〜6ヒドロキシ脂肪族、−R2、ハロゲン、−CN、−NO2、−OR、−SR、−NR2、−S(O)2R、−S(O)2NR2、−S(O)R、−C(O)R、−C(O)OR、−C(O)NR2、−C(O)N(R)OR、−OC(O)R、−OC(O)NR2、−N(R)C(O)OR、−N(R)C(O)R、−N(R)C(O)NR2、または−N(R)S(O)2Rであり;
L1は、共有結合、またはC1〜6の二価の飽和もしくは不飽和の、直鎖もしくは分枝鎖の炭化水素鎖であり、ここで該鎖の1個もしくは2個のメチレン単位は、必要に応じて独立して、−N(R)−、−N(R)C(O)−、−C(O)N(R)−、−N(R)S(O)2−、−S(O)2N(R)−、−O−、−C(O)−、−OC(O)−、−C(O)O−、−S−、−S(O)−もしくは−S(O)2−によって置き換えられており;
mは、0〜2であり;
nは、0〜4であり;
pは、0〜3であり;そして
各Rは独立して、水素であるか、またはC1〜6脂肪族、フェニル、窒素、酸素、および硫黄から独立して選択される1個〜2個のヘテロ原子を有する4員〜7員の飽和もしくは部分不飽和の複素環式、ならびに窒素、酸素、および硫黄から独立して選択される1個〜4個のヘテロ原子を有する5員〜6員のヘテロアリール環から選択される必要に応じて置換された基であるか、あるいは
同じ窒素上の2個のR基は、これらの介在する原子と一緒になって、該窒素に加えて、窒素、酸素、および硫黄から独立して選択される0個〜3個のヘテロ原子を有する4員〜7員の飽和、部分不飽和、もしくはヘテロアリールの環を形成する、
化合物またはその薬学的に受容可能な塩。 - L1は共有結合である、前出の請求項のいずれか1項に記載の化合物。
- L1は−C(O)−である、請求項1〜4のいずれか1項に記載の化合物。
- R3はCy1である、前出の請求項のいずれか1項に記載の化合物。
- R5はCy2である、前出の請求項のいずれか1項に記載の化合物。
- 少なくとも1個のR8は、ハロゲン、−CN、またはヒドロキシメチルである、前出の請求項のいずれか1項に記載の化合物。
- 環Aは、窒素、酸素、および硫黄から独立して選択される1個〜3個のヘテロ原子を有する5員ヘテロアリール環である、前出の請求項のいずれか1項に記載の化合物。
- 環Aはピラゾリルである、請求項14に記載の化合物。
- nは2〜3である、請求項16に記載の化合物。
- 前記化合物は、本明細書の表1に記載される化合物から選択される、請求項1に記載の化合物、またはその薬学的に受容可能な塩。
- 前出の請求項のいずれか1項に記載の化合物、またはその薬学的に受容可能な塩、および薬学的に受容可能なキャリア、アジュバント、またはビヒクルを含有する、薬学的組成物。
- TYK2を生物学的サンプルにおいて阻害する方法であって、該サンプルを、請求項1〜18のいずれか1項に記載の化合物、またはその薬学的に受容可能な塩と接触させる工程を包含する、方法。
- TYK2媒介性の障害、疾患、または状態を、患者において処置する方法であって、該患者に、請求項19に記載の薬学的組成物を投与する工程を包含する、方法。
- 前記障害は、自己免疫障害、炎症性障害、増殖性障害、内分泌性障害、神経学的障害、または移植に関連する障害から選択される、請求項21に記載の方法。
- 前記障害は自己免疫障害である、請求項22に記載の方法。
- 前記自己免疫障害は、1型糖尿病、全身性エリテマトーデス、多発性硬化症、乾癬、クローン病、潰瘍性大腸炎、炎症性腸疾患および強直性脊椎炎から選択される、請求項23に記載の方法。
- 前記障害は炎症性障害である、請求項22に記載の方法。
- 前記炎症性障害は、関節リウマチ、喘息、慢性閉塞性肺疾患、乾癬、クローン病、潰瘍性大腸炎、および炎症性腸疾患から選択される、請求項25に記載の方法。
- 前記障害は増殖性障害である、請求項22に記載の方法。
- 前記増殖性障害は血液学的がんである、請求項27に記載の方法。
- 前記増殖性障害は白血病である、請求項27に記載の方法。
- 前記白血病はT細胞白血病である、請求項29に記載の方法。
- 前記T細胞白血病はT細胞急性リンパ芽球性白血病(T−ALL)である、請求項30に記載の方法。
- 前記増殖性障害は、TYK2における1つまたはそれより多くの活性化変異に関連する、請求項27に記載の方法。
- 前記障害は移植に関連する、請求項22に記載の方法。
- 前記障害は、移植拒絶または対宿主性移植片病である、請求項33に記載の方法。
- 前記障害は内分泌性障害である、請求項22に記載の方法。
- 前記内分泌性障害は、多嚢胞性卵巣症候群、クルゾン症候群、または1型糖尿病である、請求項35に記載の方法。
- 前記障害は神経学的障害である、請求項22に記載の方法。
- 前記神経学的障害はアルツハイマー病である、請求項37に記載の方法。
- 前記障害は、I型インターフェロン、IL−10、IL−12、またはIL−23のシグナル伝達に関連する、請求項21に記載の方法。
- 前記増殖性障害はリンパ球増殖性疾患である、請求項27に記載の方法。
- 前記リンパ球増殖性疾患は、リンパ腫様丘疹症または未分化大細胞リンパ腫である、請求項40に記載の方法。
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WO2021193224A1 (ja) * | 2020-03-24 | 2021-09-30 | 国立大学法人東海国立大学機構 | 遺伝性対側性色素異常症治療用医薬組成物、遺伝性対側性色素異常症モデルマウス、および、遺伝性対側性色素異常症治療用化合物のスクリーニング方法 |
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US20210047319A1 (en) | 2021-02-18 |
US20170066763A1 (en) | 2017-03-09 |
TW201718576A (zh) | 2017-06-01 |
TWI707852B (zh) | 2020-10-21 |
EP3344624B1 (en) | 2023-10-25 |
EP4327809A3 (en) | 2024-04-17 |
US20230074228A1 (en) | 2023-03-09 |
EP4327809A2 (en) | 2024-02-28 |
US10023571B2 (en) | 2018-07-17 |
JP2019172690A (ja) | 2019-10-10 |
EP3344624A4 (en) | 2019-01-16 |
US20180354949A1 (en) | 2018-12-13 |
JP6802263B2 (ja) | 2020-12-16 |
EP3344624A1 (en) | 2018-07-11 |
US10781204B2 (en) | 2020-09-22 |
JP2021130712A (ja) | 2021-09-09 |
EP3344624B8 (en) | 2023-11-29 |
HK1256997A1 (zh) | 2019-10-11 |
WO2017040757A1 (en) | 2017-03-09 |
US11434240B2 (en) | 2022-09-06 |
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