JP2014510037A - ジアリールアセチレンヒドラジドを含有するチロシンキナーゼ阻害剤 - Google Patents
ジアリールアセチレンヒドラジドを含有するチロシンキナーゼ阻害剤 Download PDFInfo
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- JP2014510037A JP2014510037A JP2013549896A JP2013549896A JP2014510037A JP 2014510037 A JP2014510037 A JP 2014510037A JP 2013549896 A JP2013549896 A JP 2013549896A JP 2013549896 A JP2013549896 A JP 2013549896A JP 2014510037 A JP2014510037 A JP 2014510037A
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- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
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- C—CHEMISTRY; METALLURGY
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Abstract
Description
本出願は、2011年1月21日に出願された、参照により本明細書に組み込まれるインド特許出願第184/MUM/2011号の利益を主張する。
タンパク質チロシンキナーゼは現在、いくつかの障害の治療における、特に増殖性障害の治療における薬物開発のための重要な分子標的と認識されている。チロシンキナーゼ活性の調節不全は、それによって癌細胞が、成長、増殖、及び生存に対する正常な生理的制約を逃れるような主要機構として現れる。
・米国特許第5,521,184号('184特許):メタンスルホン酸4-[(メチル-1-ピペラジニル)メチル]-N-[4-メチル-3-[[4-(3-ピリジニル)-2-ピリミジニル]アミノ]-フェニル]ベンズアミド(イマチニブメシラート、Gleevec(登録商標))を例示している
・米国特許第7,169,791号('791特許):4-メチル-N-[3-(4-メチル-イミダゾール-1-イル)-5-トリフルオロメチル-フェニル]-3-(4-ピリジン-3-イル-ピリミジン-2-イルアミノ)-ベンズアミド(ニロチニブ、Tasigna(登録商標))を例示している
・米国特許第6,596,746号('746特許):N-(2-クロロ-6-メチルフェニル)-2-(6-(4-(2-ヒドロキシエチル)ピペラジン-1-イル)-2-メチルピリミジン-4-イルアミノ)チアゾール-5-カルボキサミド(ダサチニブ、Sprycel(登録商標))を例示している
式中、
環Qがピリジルである場合、環Pはヘテロアリールであるという条件で、環P及び環Qは独立に、1以上の同一又は異なるラジカルR3によって任意に置換された、6から14個の炭素原子を有するアリール環、又は、それぞれ独立にO、S、及びNから選択される1から4個のヘテロ原子を含有する5から14員のヘテロアリール環から選択され;
R1及びR2は独立に、水素、-C1〜8-アルキル、-C2〜10-アルケニル、-C2〜12-アルキニル、-C3〜12-シクロアルキル、-C4〜12-シクロアルキルアルキル、-C3〜12-シクロアルケニル、アリール、ヘテロアリール、アリールアルキル、及びヘテロアリールアルキルラジカルからなる群から選択され(ここでは、該アリール環は、6から14個の炭素原子を含有し、該ヘテロアリール環は、O、S、及びNからそれぞれ独立に選択される1から4個のヘテロ原子を有する5から14員の環系を含有する)、かつ、1以上の同一又は異なるラジカルR3によって任意に置換され;
X及びYは独立に、C=O、C=S、及びSO2からなる群から選択され;
R3は、ハロゲン、-OH、-CN、-NO2、-N3、-C1〜8-アルキル、-C3〜12-シクロアルキル、-(C1〜8-アルキル)-C3〜12-シクロアルキル、-ヘテロシクロアルキル(O、S、及びNからそれぞれ独立に選択される1又は2個のヘテロ原子を有する3から12個の環原子を含有する)、-(C1〜8-アルキル)-ヘテロシクロアルキル(O、S、及びNからそれぞれ独立に選択される1又は2個のヘテロ原子を有する3から12個の環原子を含有する)、-O-C1〜8-アルキル、-O-C3〜12-シクロアルキル、-O-アリール、-O-ヘテロアリール、-C1〜8アルキル-O-C1〜8アルキル、-O-C1〜8アルキル-O-C1〜8アルキル、-O-C1〜8アルキル-NH(C1〜8アルキル)、-O-C1〜8アルキル-N(C1〜8アルキル)2、-O-C1〜8アルキル-(ヘテロアリール)、-C(O)-C1〜8アルキル、-COOH、-C(O)NH2、-C(O)NH-C1〜8アルキル、-C(O)N(C1〜8アルキル)2、-C(O)O-C1〜8アルキル、-C1〜8ハロアルキル、-C2〜10アルケニル、-C2〜12アルキニル、-OC(O)-NH2、-OC(O)-NH(C1〜8アルキル)、-OC(O)-N(C1〜8アルキル)2、-NH2、-NH(C1〜8アルキル)、-N(C1〜8アルキル)2、-NH-SO2-C1〜8アルキル、-N(C1〜8アルキル)-SO2-C1〜8アルキル、-NH-C(O)-(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-(C1〜8アルキル)、-NH-C(O)O-C1〜8アルキル、-N(C1〜8アルキル)-C(O)O-C1〜8アルキル、-NH-C(O)-NH2、-NH-C(O)-NH(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-NH(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-N(C1〜8アルキル)2、-NH-C(O)-NH-SO2-C1〜8アルキル、-N(C1〜8アルキル)-C(O)-NHSO2-C1〜8アルキル、-N(C1〜8アルキル)-C(O)-N(C1〜8アルキル)-SO2-C1〜8アルキル、-S-C1〜8アルキル、-S(O)-C1〜8アルキル、-SO2-C1〜8アルキル、-S-アリール、-S(O)-アリール、SO2-アリール、-SO2NH2、-SO2NH-(C1〜8アルキル)、-SO2N(C1〜8アルキル)2;-アリール、-(C1〜4-アルキル)-アリール、ヘテロアリール、又は-(C1〜4-アルキル)-ヘテロアリール基からなる群から選択され、ここでは、該アリール環は、6から14個の炭素原子を含有し、該ヘテロアリール環は、O、S、及びNからそれぞれ独立に選択される1から4個のヘテロ原子を有する5から14員の環系を含有し、前述のR3基はそれぞれ、C1〜4-アルキル、C1〜4-アルコキシ、C1〜4-ハロアルキル、-OH、-COOH、-CN、-NO2、ハロ、-NH2、及び-SO2NH2からなる群から選択される単一の基で任意に置換され得る。
本発明は、式(I)の化合物
式中、
環Qがピリジルである場合、環Pはヘテロアリールであるという条件で、環P及び環Qは独立に、1以上の同一又は異なるラジカルR3によって任意に置換された、6から14個の炭素原子を有するアリール環、又は、それぞれ独立にO、S、及びNから選択される1から4個のヘテロ原子を含有する5から14員のヘテロアリール環から選択され;
R1及びR2は独立に、水素、-C1〜8-アルキル、-C2〜10-アルケニル、-C2〜12-アルキニル、-C3〜12-シクロアルキル、-C4〜12-シクロアルキルアルキル、-C3〜12-シクロアルケニル、アリール、ヘテロアリール、アリールアルキル、及びヘテロアリールアルキルラジカルからなる群から選択され(ここでは、該アリール環は、6から14個の炭素原子を含有し、該ヘテロアリール環は、O、S、及びNからそれぞれ独立に選択される1から4個のヘテロ原子を有する5から14員の環系を含有する)、かつ、1以上の同一又は異なるラジカルR3によって任意に置換され;
X及びYは独立に、C=O、C=S、及びSO2からなる群から選択され;
R3は、ハロゲン、-OH、-CN、-NO2、-N3、-C1〜8-アルキル、-C3〜12-シクロアルキル、-(C1〜8-アルキル)-C3〜12-シクロアルキル、-ヘテロシクロアルキル(O、S、及びNからそれぞれ独立に選択される1又は2個のヘテロ原子を有する3から12個の環原子を含有する)、-(C1〜8-アルキル)-ヘテロシクロアルキル(O、S、及びNからそれぞれ独立に選択される1又は2個のヘテロ原子を有する3から12個の環原子を含有する)、-O-C1〜8-アルキル、-O-C3〜12-シクロアルキル、-O-アリール、-O-ヘテロアリール、-C1〜8アルキル-O-C1〜8アルキル、-O-C1〜8アルキル-O-C1〜8アルキル、-O-C1〜8アルキル-NH(C1〜8アルキル)、-O-C1〜8アルキル-N(C1〜8アルキル)2、-O-C1〜8アルキル-(ヘテロアリール)、-C(O)-C1〜8アルキル、-COOH、-C(O)NH2、-C(O)NH-C1〜8アルキル、-C(O)N(C1〜8アルキル)2、-C(O)O-C1〜8アルキル、-C1〜8ハロアルキル、-C2〜10アルケニル、-C2〜12アルキニル、-OC(O)-NH2、-OC(O)-NH(C1〜8アルキル)、-OC(O)-N(C1〜8アルキル)2、-NH2、-NH(C1〜8アルキル)、-N(C1〜8アルキル)2、-NH-SO2-C1〜8アルキル、-N(C1〜8アルキル)-SO2-C1〜8アルキル、-NH-C(O)-(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-(C1〜8アルキル)、-NH-C(O)O-C1〜8アルキル、-N(C1〜8アルキル)-C(O)O-C1〜8アルキル、-NH-C(O)-NH2、-NH-C(O)-NH(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-NH(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-N(C1〜8アルキル)2、-NH-C(O)-NH-SO2-C1〜8アルキル、-N(C1〜8アルキル)-C(O)-NHSO2-C1〜8アルキル、-N(C1〜8アルキル)-C(O)-N(C1〜8アルキル)-SO2-C1〜8アルキル、-S-C1〜8アルキル、-S(O)-C1〜8アルキル、-SO2-C1〜8アルキル、-S-アリール、-S(O)-アリール、SO2-アリール、-SO2NH2、-SO2NH-(C1〜8アルキル)、-SO2N(C1〜8アルキル)2;-アリール、-(C1〜4-アルキル)-アリール、ヘテロアリール、又は-(C1〜4-アルキル)-ヘテロアリール基からなる群から選択され、ここでは、該アリール環は、6から14個の炭素原子を含有し、該ヘテロアリール環は、O、S、及びNからそれぞれ独立に選択される1から4個のヘテロ原子を有する5から14員の環系を含有し、前述のR3基はそれぞれ、C1〜4-アルキル、C1〜4-アルコキシ、C1〜4-ハロアルキル、-OH、-COOH、-CN、-NO2、ハロ、-NH2、及び-SO2NH2からなる群から選択される単一の基で任意に置換され得る。
以下の実施例は、本発明を、その範囲を制限することなく例示するための助けとなる。
実施例で使用するいくつかの出発化合物の調製方法は、参考例として記載されている。
一般式(I)の化合物を含めて、本明細書に記述する化合物は、当技術分野で公知の技術によって、例えばスキーム1〜7に表す反応スキームを通して調製することができる。さらに、以下の実施例では、具体的な酸、塩基、試薬、カップリング剤、溶媒などが挙げられる場合、他の適切な酸、塩基、試薬、カップリング剤なども使用することができ、これらは本発明の範囲内に含まれることを理解されたい。反応条件、例えば、温度、反応時間、又はこれらの組み合わせに対する改変は、本発明の一部と想定される。
DMSO-ジメチルスルホキシド;DMF-N,N-ジメチルホルムアミド;THF-テトラヒドロフラン;Pd(PPh3)4-テトラキス(トリフェニルホスフィン)パラジウム;CuI-ヨウ化銅(I)。
3-エチニル-4-メチル安息香酸メチル
3-エチニル-4-フルオロ安息香酸メチル
3-エチニル-4-メトキシ安息香酸メチル
4-メチル-3-[(キノリン-3-イル)エチニル]安息香酸
4-メチル-3-[(ピリジン-3-イル)エチニル]安息香酸
4-メチル-3-[(キノリン-3-イル)エチニル]安息香酸
4-メチル-3-[(ベンゾチアゾール-3-イル)エチニル]安息香酸
4-フルオロ-3-[(キノリン-3-イル)エチニル]安息香酸
4-メトキシ-[(3-キノリン-3-イル)エチニル]安息香酸
4-メチル-3-[(ピリド(2,3-b)ピラジン-7-イル)エチニル]安息香酸
4-メチル-3-[(6-メチル-3-キノリン-3-イル)エチニル]安息香酸
4-メチル-3-[(ナフト-3-イル)エチニル]安息香酸
4-メチル-3-[5-tert-ブチル-2-フェニル-2H-ピラゾール-3-イルエチニル]安息香酸
4-メチル-3-[(6-クロロ-3-キノリン-3-イル)エチニル]安息香酸
4-メチル-3-[(6-フルオロ-3-キノリン-3-イル)エチニル]安息香酸
4-メチル-3-[(2-キノリン-3-イル)エチニル]安息香酸
4-メチル-3-[2-(3-キノリル)エチニル]ベンゾヒドラジド
4-メチル-3-[2-(3-ピリジル)エチニル]ベンゾヒドラジド
4-メチル-3-[2-(6-キノリル)エチニル]ベンゾヒドラジド
3-[2-(1,3-ベンゾチアゾール-2-イル)エチニル]-4-メチルベンゾヒドラジド
4-フルオロ-3-[2-(3-キノリル)エチニル]ベンゾヒドラジド
4-メトキシ-3-[2-(3-キノリル)エチニル]ベンゾヒドラジド
4-メチル-3-[(ピリド(2,3-b)ピラジン-7-イル)エチニル]ベンゾヒドラジド
4-メチル-3-[(6-メチル-3-キノリン-3-イル)エチニル]ベンゾヒドラジド
4-メチル-3-[(ナフト-3-イル)エチニル]ベンゾヒドラジド
4-メチル-3-[5-tert-ブチル-2-フェニル-2H-ピラゾール-3-イルエチニル]ベンゾヒドラジド
4-メチル-3-[(6-クロロ-3-キノリン-3-イル)エチニル]ベンゾヒドラジド
4-メチル-3-[(6-フルオロ-3-キノリン-3-イル)エチニル]ベンゾヒドラジド
4-メチル-3-[(2-キノリン-3-イル)エチニル]ベンゾヒドラジド
N'-(3-ヨード-4-メチルベンゾイル)-2,4,6-トリクロロベンゾヒドラジド
N'-(2-クロロ-6-メチルベンゾイル)-3-ヨード-4-メチルベンゾヒドラジド
3-ヨード-4-メチル-N'-[4-[(4-メチルピペラジン-1-イル)メチル]-3-(トリフルオロメチル)ベンゾイル]ベンゾヒドラジド
3-ヨード-N'-(2-ヨード-6-メチルベンゾイル)-4-メチルベンゾヒドラジド
N'-(2,6-ジクロロベンゾイル)-3-ヨード-4-メチルベンゾヒドラジド
N'-[2,6-ビス(トリフルオロメチル)ベンゾイル]-3-ヨード-4-メチルベンゾヒドラジド
3-ヨード-4-メチル-N'-[3-(4-メチルイミダゾール-1-イル)-5-(トリフルオロメチル)ベンゾイル]ベンゾ-ヒドラジド
N'-(3-ヨード-4-メチルベンゾイル)-2,4,6-トリメチルベンゾヒドラジド
N'-(2-ブロモ-6-メチルベンゾイル)-3-ヨード-4-メチルベンゾヒドラジド
3-ヨード-N'-(2-メトキシ-6-メチルベンゾイル)-4-メチルベンゾヒドラジド
N'-(2-フルオロ-6-メチルベンゾイル)-3-ヨード-4-メチルベンゾヒドラジド
N'-(2-クロロ-6-メチルベンゾイル)-4-フルオロ-3-ヨードベンゾヒドラジド
N'-(2-クロロ-6-メチルベンゾイル)-3-ヨード-4-メトキシベンゾヒドラジド
N'-(2-フルオロ-6-ヨードベンゾイル)-3-ヨード-4-メチルベンゾヒドラジド
N'-[2-クロロ-6-(トリフルオロメチル)ベンゾイル]-3-ヨード-4-メチルベンゾヒドラジド
N'-[2-フルオロ-6-(トリフルオロメチル)ベンゾイル]-3-ヨード-4-メチルベンゾヒドラジド
N-tert-ブチル-N'-(2-クロロ-6-メチルベンゾイル)-3-ヨード-4-メチルベンゾヒドラジド
N-メチル-N'-(2-クロロ-6-メチルベンゾイル)-3-ヨード-4-メチルベンゾヒドラジド
6-ブロモ-2-ピリジンカルボン酸メチル
5-エチニル-2-チオフェンカルボン酸メチル
3-エチニル-4-ピラゾールカルボン酸メチル
2-エチニル-5-チアゾールカルボン酸メチル
6-[(キノリン-3-イル)エチニル]ピリジン-2-カルボン酸
5-[(キノリン-3-イル)エチニル]チオフェン-2-カルボン酸
3-[(キノリン-3-イル)エチニル]ピラゾール-4-カルボン酸
2-[(キノリン-3-イル)エチニル]チアゾール-5-カルボン酸
4-メチル-3-[(キノリン-3-イル)エチニル]チオ安息香酸
2,4,6-トリクロロ-N'-[4-メチル-3-[2-(3-キノリル)エチニル]ベンゾイル]ベンゾヒドラジド
方法A:
4-メチル-3-[(キノリン-3-イル)エチニル]安息香酸と2,4,6-トリクロロベンゾヒドラジド(シアノホスホン酸ジエチル中)との反応によって、2,4,6-トリクロロ-N'-[4-メチル-3-[2-(3-キノリル)エチニル]ベンゾイル]ベンゾヒドラジドも調製した。この縮合反応は、方法Aに記述したのと同様の方式で実施した。
2,4,6-トリクロロ-N'-[3-[2-(2-イミダゾ[1,2--a]ピラジン-3-イル)エチニル)]]-4-メチル-ベンゾイル]ベンゾヒドラジド
N'-(2-クロロ-6-メチルベンゼンスルホニル)-4-メチル-3-[2-(3-キノリル)エチン-イル]ベンゾヒドラジド
N'-(2-クロロ-6-メチルベンゾイル)-6-[2-(3-キノリル)エチニル]ピリジン-2-カルボン酸ヒドラジド
2-クロロ-6-メチル-N'-[4-メチル-3-[2-(3-キノリル)エチニル]ベンゾイル]チオベンゾ-ヒドラジド
(インビトロ細胞増殖アッセイ)
K562/U937細胞(ウェルあたり2×104)を、試験化合物/ビヒクルと共に、総体積200μLの培地中で、5% CO2と共に37℃でインキュベートした。4日目に、20μL MTT 5mg/mlを加え、細胞を4〜5時間インキュベートし、それに続いて、0.06N HCl中に調製した100μLの10% SDSを添加した。細胞を終夜、5% CO2と共に37℃でインキュベートした。5日目に、参照波長として630nmを用いて、570nmで光学密度を測定した。ビヒクル処理されたウェルにおける光学密度を、試験化合物処理されたウェルの光学密度と比較した。
キナーゼアッセイは、Millipore Pharma Services社(その英国薬理学研究室にて)によって実施された。
最終反応体積25μLにおいて、Abl(ヒト)(5〜10mU)を、8mM MOPS pH7.0、0.2mM EDTA、50μM EAIYAAPFAKKK、10mM Mg(OAc)2、及び[γ-33P-ATP][比活性およそ500cpm/pmol、必要とされる濃度]と共にインキュベートする。この反応は、MgATP混合物の添加によって開始する。室温で40分間インキュベートした後、5μLの3%リン酸溶液の添加によって反応を停止させる。次いで、10μLの反応物を、P30フィルターマットにスポットし、75mMリン酸中で5分間3回、及びメタノール中で1回洗浄し、その後乾燥及びシンチレーション測定を行う。
手順は、Ablキナーゼについて上に記述したのとまったく同じであるが、Abl(ヒト)キナーゼを、変異型Abl(Q252H)(ヒト)、Abl(Y253F)(ヒト)、Abl(T315I)(ヒト)、Abl(M351T)(ヒト)、及びAbl(H396P)(ヒト)キナーゼに置き換える。
最終反応体積25μLにおいて、Lck(ヒト)(5〜10mU)を、50mM Tris pH 7.5、0.1mM EGTA、0.1mM Na3VO4、250μM
最終反応体積25μLにおいて、Lyn(ヒト)(5〜10mU)を、50mM Tris pH 7.5、0.1mM EGTA、0.1mM Na3VO4、0.1% β-メルカプトエタノール、0.1mg/mlポリ(Glu,tyr)4:1、10mM Mg(OAc)2、及び[γ-33P-ATP](比活性およそ500cpm/pmol、必要とされる濃度)と共にインキュベートする。この反応は、MgATP混合物の添加によって開始する。室温で40分間インキュベートした後、5μLの3%リン酸溶液の添加によって反応を停止させる。次いで、10μLの反応物を、フィルターマットAにスポットし、75mMリン酸中で5分間3回、及びメタノール中で1回洗浄し、その後乾燥及びシンチレーション測定を行う。
各キナーゼアッセイ内で、コントロール値の割合を、そのキナーゼについての平均の最小(0%)及び最大(100%)コントロール(コントロールにつきn=4)に基づいて、各試験化合物の生データポイントについて算出した(試料-平均最小値/平均最大値-平均最小値×100%)。これらの値から、阻害率を算出した(100-コントロールの平均割合)。
Claims (10)
- 式(I)の化合物
(式中、
環Qがピリジルである場合、環Pはヘテロアリールであるという条件で、環P及び環Qは独立に、1以上の同一又は異なるラジカルR3によって任意に置換された、6から14個の炭素原子を有するアリール環、又は、それぞれ独立にO、S、及びNから選択される1から4個のヘテロ原子を含有する5から14員のヘテロアリール環から選択され;
R1及びR2は独立に、水素、-C1〜8-アルキル、-C2〜10-アルケニル、-C2〜12-アルキニル、-C3〜12-シクロアルキル、-C4〜12-シクロアルキルアルキル、-C3〜12-シクロアルケニル、アリール、ヘテロアリール、アリールアルキル、及びヘテロアリールアルキルラジカルからなる群から選択され(ここでは、該アリール環は、6から14個の炭素原子を含有し、該ヘテロアリール環は、O、S、及びNからそれぞれ独立に選択される1から4個のヘテロ原子を伴う5から14員の環系を含有する)、かつ、1以上の同一又は異なるラジカルR3によって任意に置換され;
X及びYは独立に、C=O、C=S、及びSO2からなる群から選択され;
R3は、ハロゲン、-OH、-CN、-NO2、-N3、-C1〜8-アルキル、-C3〜12-シクロアルキル、-(C1〜8-アルキル)-C3〜12-シクロアルキル、-ヘテロシクロアルキル(O、S、及びNからそれぞれ独立に選択される1又は2個のヘテロ原子を有する3から12個の環原子を含有する)、-(C1〜8-アルキル)-ヘテロシクロアルキル(O、S、及びNからそれぞれ独立に選択される1又は2個のヘテロ原子を有する3から12個の環原子を含有する)、-O-C1〜8-アルキル、-O-C3〜12-シクロアルキル、-O-アリール、-O-ヘテロアリール、-C1〜8アルキル-O-C1〜8アルキル、-O-C1〜8アルキル-O-C1〜8アルキル、-O-C1〜8アルキル-NH(C1〜8アルキル)、-O-C1〜8アルキル-N(C1〜8アルキル)2、-O-C1〜8アルキル-(ヘテロアリール)、-C(O)-C1〜8アルキル、-COOH、-C(O)NH2、-C(O)NH-C1〜8アルキル、-C(O)N(C1〜8アルキル)2、-C(O)O-C1〜8アルキル、-C1〜8ハロアルキル、-C2〜10アルケニル、-C2〜12アルキニル、-OC(O)-NH2、-OC(O)-NH(C1〜8アルキル)、-OC(O)-N(C1〜8アルキル)2、-NH2、-NH(C1〜8アルキル)、-N(C1〜8アルキル)2、-NH-SO2-C1〜8アルキル、-N(C1〜8アルキル)-SO2-C1〜8アルキル、-NH-C(O)-(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-(C1〜8アルキル)、-NH-C(O)O-C1〜8アルキル、-N(C1〜8アルキル)-C(O)O-C1〜8アルキル、-NH-C(O)-NH2、-NH-C(O)-NH(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-NH(C1〜8アルキル)、-N(C1〜8アルキル)-C(O)-N(C1〜8アルキル)2、-NH-C(O)-NH-SO2-C1〜8アルキル、-N(C1〜8アルキル)-C(O)-NHSO2-C1〜8アルキル、-N(C1〜8アルキル)-C(O)-N(C1〜8アルキル)-SO2-C1〜8アルキル、-S-C1〜8アルキル、-S(O)-C1〜8アルキル、-SO2-C1〜8アルキル、-S-アリール、-S(O)-アリール、SO2-アリール、-SO2NH2、-SO2NH-(C1〜8アルキル)、-SO2N(C1〜8アルキル)2;-アリール、-(C1〜4-アルキル)-アリール、ヘテロアリール、又は-(C1〜4-アルキル)-ヘテロアリール基からなる群から選択され、ここでは、該アリール環は、6から14個の炭素原子を含有し、該ヘテロアリール環は、O、S、及びNからそれぞれ独立に選択される1から4個のヘテロ原子を伴う5から14員の環系を含有し、前述のR3基はそれぞれ、C1〜4-アルキル、C1〜4-アルコキシ、C1〜4-ハロアルキル、-OH、-COOH、-CN、-NO2、ハロ、-NH2、及び-SO2NH2からなる群から選択される単一の基で任意に置換され得る)。 - 環P及び環Qが独立に、1以上の同一又は異なるラジカルR3によって任意に置換された、フェニル、ナフチル、ピリジン、チオフェン、ピラゾール、チアゾール、キノリン、ベンゾチアゾール、ピラジン、ピリミジン、キノキサリン、キナゾリン、イミダゾ[1,2-a]ピラジン、イミダゾ[1,2-a]ピリダジン、イミダゾ[1,2-a]ピリジン、ピラゾロ[1,5-a]ピリミジン、ピリド[2,3-b]ピラジン、シンノリン、フタラジンから選択される、請求項1記載の化合物。
- R1が、水素、-C1〜8-アルキル、-C2〜10-アルケニル、-C2〜12-アルキニル、-C3〜12-シクロアルキル、-C4〜12-シクロアルキルアルキル、又は-C3〜12-シクロアルケニル基から選択される、請求項1又は2記載の化合物。
- R2が、アリール、ヘテロアリール、アリールアルキル、又はヘテロアリールアルキルラジカルから選択され(ここでは、該アリール環は、6から14個の炭素原子を含有し、該ヘテロアリール環は、O、S、及びNからそれぞれ独立に選択される1から4個のヘテロ原子を伴う5から14員の環系を含有する)、かつ、1以上の同一又は異なるラジカルR3によって任意に置換される、請求項1、2、又は3記載の化合物。
- R2が、1以上の同一又は異なるラジカルR3によって任意に置換された、フェニル、ピリジン、チオフェン、又はピラゾールから選択されるアリール又はヘテロアリール環である、請求項4記載の化合物。
- XとYが両方ともC=Oである、請求項1から5のいずれか1項記載の化合物。
- XがC=Sであり、かつYがC=Oである、請求項1から5記載の化合物。
- XがC=Oであり、かつYがSO2である、請求項1から5記載の化合物。
- R3が、ハロゲン、-OH、-CN、-NO2、-N3、-C1〜8-アルキル、-C3〜12-シクロアルキル、-O-C1〜8アルキル、-O-C3〜12-シクロアルキル、-C1〜8-ハロアルキル、-(C1〜8-アルキル)-ヘテロシクロアルキル(O、S、及びNからそれぞれ独立に選択される1又は2個のヘテロ原子を有する3から12個の環原子を含有する)、アリール基、ヘテロアリール基、又は-(C1〜4-アルキル)-ヘテロアリール基からなる群から選択され、ここでは、該アリール環は、6から14個の炭素原子を含有し、該ヘテロアリール環は、O、S、及びNからそれぞれ独立に選択される1から4個のヘテロ原子を伴う5から14員の環系を含有し;前述のR3基はそれぞれ、C1〜4-アルキル、C1〜4-アルコキシ、C1〜4-ハロアルキル、-OH、-COOH、-CN、-NO2、ハロ、-NH2、及び-SO2NH2からなる群から選択される単一の基で任意に置換され得る、請求項1から8のいずれか1項記載の化合物。
- XとYがC=Oであり、R1が水素であり、R2、環P、及び環Qが、アリール又はヘテロアリールである、式(I)の化合物。
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
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R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |