JP6710213B2 - レチノイド関連オーファン受容体ガンマ(rorガンマ(t))のインバースアゴニストとしてのベンゾイミダゾールスルホンアミド誘導体 - Google Patents
レチノイド関連オーファン受容体ガンマ(rorガンマ(t))のインバースアゴニストとしてのベンゾイミダゾールスルホンアミド誘導体 Download PDFInfo
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Classifications
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
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- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
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- C07D249/18—Benzotriazoles
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- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
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- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
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- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D471/10—Spiro-condensed systems
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Description
・Lは、単結合又はメチレン基CH2を表し、
・Xは、以下の環状基を表し:
・構成要素Q1、Q2及びQ3のうちの1つ若しくは2つは、窒素原子及び-CR2a基に相当する他の構成要素を表し、又は構成要素Q1、Q2及びQ3のそれぞれは、-CR2a基に相当し、
・R1は、直鎖状又は分岐状C3〜C5アルキル基、C3〜C5シクロアルキル基、直鎖状又は分岐状C2〜C5アルケニル基、(C1)アルキル(C3〜C5)シクロアルキル基、C4〜C5ヘテロシクロアルキル基、(C1)アルキル(C4〜C6)ヘテロシクロアルキル基を表し、
・R2は、水素原子又はハロゲン原子、直鎖状又は分岐状C1〜C5アルキル基、直鎖状又は分岐状C2〜C4アルケニル基、C1〜C4アルコキシ基、シアノ基-CN、-C(=O)R'2基を表し、R'2は、C1〜C3アルコキシ基、-CF3基を表し;前記アルキル、アルケニル及びアルコキシ基は、場合により1個又は複数のハロゲン原子で置換されており;
・R2aは、水素原子又はハロゲン原子、直鎖状又は分岐状C1〜C5アルキル基、直鎖状又は分岐状C2〜C4アルケニル基、C1〜C4アルコキシ基、-CN基、ヒドロキシル基-OH、-CH(R3a)OH基、カルボン酸基-COOH、カルバモイル基-CONR2cR2d、アミド基-NR2cCOR2d、-SO2R2c基、-SOR2c基、-S(=O)(=NH-R2c)基を表し、前記アルキル、アルケニル及びアルコキシ基は、場合により1個又は複数のハロゲン原子で置換されており、
・R2c及びR2dは、同一であっても異なっていてもよく、水素原子又は直鎖状若しくは分岐状C1〜C5アルキル基を表し;
・R3aは、水素原子又は直鎖状若しくは分岐状C1〜C5アルキル基を表し;
・R3は、水素原子又は(CHR6)n-(Z)o-(CHR'6)p-R7基、CH=R7基又は-C=CH-R7基を表し、
・n、o及びpは、同一であっても異なっていてもよく、0又は1から3の範囲の自然数を表し、
・Zは、メチレン基-CH2-、アミノ基-NH-及び酸素原子-O-から選択される二価基を表し、
・R6及びR'6は、同一であっても異なっていてもよく、水素原子、メチル基-CH3、-OH基、C1ヒドロキシアルキル基、カルボン酸官能基-COOHを表し、
・R7は:
- 水素原子又はハロゲン原子、
- R'7が(C1)アルキル(C6)ヘテロ環を表すCOOR'7基、
- 1個又は複数のハロゲン原子、1個又は複数の直鎖状又は分岐状C1〜C3アルキル基、1個又は複数の-OH基、1個又は複数のカルボニル官能基、1個又は複数の直鎖状又は分岐状C1〜C4ヒドロキシアルキル基、1個又は複数のアミノ基、1個又は複数の-C(=O)R7a基、1個又は複数のS(=O)2R7a基で任意選択で置換されている非カチオン性ヘテロ環式基であって、R7aは、直鎖状若しくは分岐状C1〜C3アルキル基、直鎖状若しくは分岐状C1〜C3アルコキシ基又はアミノ基N(R8a)(R8b)を表す、非カチオン性ヘテロ環式基、
- 1個若しくは複数のC1アルキル基、1個若しくは複数のハロゲン原子、シアノ基-CN又は1個若しくは複数の-COR9基で任意選択で置換されている非カチオン性C3〜C6シクロアルキル基であって、R9は、直鎖状若しくは分岐状C1〜C3アルコキシ基又はヒドロキシル基を表す、非カチオン性C3〜C6シクロアルキル基、
- 1個若しくは複数のハロゲン原子、任意選択で、1個若しくは複数のハロゲン原子で置換されている1個若しくは複数の直鎖状若しくは分岐状C1〜C3アルキル基、1個若しくは複数のC1〜C3アルコキシ基、1個若しくは複数のアミノ基-NR11R12、1個若しくは複数の-COR11基、1個若しくは複数の-COOR11基、1個若しくは複数のアミド基-CONR11R12、1個若しくは複数の-SOR11基、1個若しくは複数の-SO2R11基、1個若しくは複数の-NHCOR11基、1個若しくは複数の-NHCOOR11基、1個若しくは複数の-SO2NR11R12基又は1個若しくは複数の-CN基で任意選択で置換されている芳香族若しくはヘテロ芳香族非カチオン性基であって、R11及びR12は、同一であっても異なっていてもよく、水素原子、ヒドロキシル基-OH、任意選択で、1個又は複数のハロゲン原子で置換されている直鎖状又は分岐状C1〜C3アルキル基を表す、芳香族若しくはヘテロ芳香族非カチオン性基、
を表し、
・R3が、-CH=R7基又は-C=CH-R7基を表す場合、R7は、水素原子、ハロゲン原子又はCOOR'7基を表さず、
・R5は、水素原子又はハロゲン原子、任意選択で、1個又は複数のハロゲン原子で置換されている直鎖状又は分岐状C1〜C3アルキル基;アミノ基-NH2、CH2R'7a基を表し、R'7aは、C1アルコキシ基、ヒドロキシル基-OH、-CH2COOH基、-CH(R5b)OH基、アミノ基-NH2、カルボン酸基-COOH、-CN基、チオキソ官能基を表し、
・R5bは、水素原子;任意選択で、1個又は複数のカルボン酸官能基で置換されている直鎖状又は分岐状C1〜C3アルキル基;シクロプロピル基を表し、
・R8a及びR8bは、同一であっても異なっていてもよく、水素原子、直鎖状若しくは分岐状C1〜C3アルキル基又はシクロプロピル基を表す。
式中:
- R7aは、直鎖状若しくは分岐状C1〜C3アルキル基、直鎖状若しくは分岐状C1〜C3アルコキシ基又はアミノ基N(R8a)(R8b)を表し、
- R8a及びR8bは、同一であっても異なっていてもよく、水素原子、直鎖状若しくは分岐状C1〜C3アルキル基又はシクロプロピル基を表し、
- R8及びR9は、同一であっても異なっていてもよく、水素原子、直鎖状又は分岐状C1〜C3アルキル基、ヒドロキシル基-OH、カルボニル官能基=O、(C1)ヒドロキシアルキル基(-CH2OH)、アミノ基NH2を表し、
- R8及びR9は、それらが結合している炭素原子と一緒になって、5-から7-員環の炭素環式環を形成できる。
- R10は、水素原子若しくはハロゲン原子、任意選択で、1個若しくは複数のハロゲン原子で置換されている直鎖状若しくは分岐状C1〜C3アルキル基、C1〜C3アルコキシ基、アミノ基-NR11R12、-COR11基、-COOR11基、アミド基-CONR11R12、-SOR11基、-SO2R11基、-NHCOR11基、-NHCOOR11基、-SO2NR11R12基又は-CN基を表し;R11及びR12は、同一であっても異なっていてもよく、水素原子、又は任意選択で、1個若しくは複数のハロゲン原子で置換されている直鎖状若しくは分岐状C1〜C3アルキル基を表し、
- mは、0又は1から3の範囲の自然数を表す。
四級アンモニウムイオンの例は、イオンN+(CH3)4であってよい。
HeLa株である株HG5LNから、RORγトランス活性化モデルが開発されており、これは、酵母のGAL4認識ドメインの五量体及びβ-グロビンプロモーターにより制御されるルシフェラーゼレポーター遺伝子を安定的に発現する。HG5LN株は、RORガンマリガンド結合ドメイン(LBD)に融合させたGAL4のDNA結合ドメイン(DBD)により安定的に遺伝子導入された。RORガンマの構成的活性を阻害する分子は、ルシフェラーゼ発現を減少させ、したがって、発光の減少を引き起こす。
このモデルで、CD4+細胞によるIL-17A分泌に対する阻害剤の効果を測定することが可能となる。細胞は、冷凍CD4+細胞(STEMCELL社、#70026)であり、ヒトの末梢血から単離され、抗CD3及び抗CD28抗体で活性化する。分泌されるIL-17Aの量は、TR-FRET(キットHTRF(登録商標)Human Interleukin 17A(Cisbio社、#64H17PEC))技術で測定する。
反応スキーム1
2-オキソ-1-(テトラヒドロピラン-4-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=179
MS:[M+H]=397
MS:[M+H]=476
MS:[M+H]=446
1-(4-メチルテトラヒドロピラン-4-イルメチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=490
MS:[M+H]=460
1-(4-フルオロテトラヒドロピラン-4-イルメチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=494
MS:[M+H]=465
1-[(1R,5S,6S)-1-(3-オキサビシクロ[3.1.0]ヘキサ-6-イル)メチル]-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=474
MS:[M+H]=444
1-オキセタン-3-イルメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=450
MS:[M+H]=419
2-オキソ-1-(2-オキソ[1,3]ジオキソラン-4-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=478
MS:[M+H]=448
2-オキソ-1-(2-オキソオキサゾリジン-5-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=477
MS:[M+H]=447
2-オキソ-1-(2-オキソテトラヒドロフラン-3-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=476
MS:[M+H]=446
2-オキソ-1-ピリジン-4-イルメチル-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=469
MS:[M-H]=437
2-オキソ-1-(テトラヒドロピラン-4-イル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=462
MS:[M+H]=432
tert-ブチル4-{5-[(4-エチルフェニル)イソブチルスルファモイル]-2-オキソ-2,3-ジヒドロベンゾイミダゾール-1-イル}ピペリジン-1-カルボキシレートの合成
MS:[M+H]=461
MS:[M+H]=531
2-オキソ-1-ピペリジン-4-イル-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
1-(1-メタンスルホニルピペリジン-4-イル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
2-オキソ-1-(テトラヒドロピラン-4-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)シクロペンチルアミド
MS:[M+H]=409
MS:[M+H]=488
MS:[M+H]=458
2-オキソ-1-(テトラヒドロピラン-4-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)(1-エチルプロピル)アミドの合成
MS:[M+H]=411
MS:[M+H]=490
MS:[M+H]=460
2-オキソ-1-(テトラヒドロピラン-4-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(2,4-ジメチルフェニル)イソブチルアミドの合成
MS:[M-H]=396
MS:[M+H]=476
MS:[M+H]=446
2-オキソ-1-(テトラヒドロピラン-4-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸シクロペンチル(2,4-ジメチルフェニル)アミドの合成
MS:[M-H]=339
MS:[M+H]=488
MS:[M+H]=458
2-オキソ-1-(テトラヒドロピラン-4-イルメチル)-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(2,4-ジメチルフェニル)(1-エチルプロピル)アミドの合成
MS:[M+H]=411
MS:[M+H]=490
MS:[M+H]=460
1-(1,1-ジオキソヘキサヒドロ-1λ6-チオピラン-4-イルメチル)-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4-エチルフェニル)イソブチルアミドの合成
MS:[M+H]=492
MS:[M+H]=462
反応スキーム2
1-オキセタン-3-イルメチル-2-オキソ-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸(4,6-ジメチルピリジン-3-イル)イソブチルアミドの合成
MS:[M-H]=340
MS:[M+H]=398
MS:[M+H]=449
MS:[M+H]=419
N,N'-カルボニルジイミダゾール(128mg;0.79mmol)を、テトラヒドロフラン(1.1ml)中の3-アミノ-N-(4,6-ジメチルピリジン-3-イル)-N-イソブチル-4-[(オキセタン-3-イルメチル)アミノ]ベンゼンスルホンアミド(110mg;0.26mmol)の溶液に添加する。反応媒体を60℃の温度にて17時間撹拌し、水で加水分解し、酢酸エチルで抽出する。
2-オキソ-1-ピリダジン-4-イルメチル-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸イソプロピル(4-メトキシ-2-メチルフェニル)アミドの合成
MS:[M-H]=355
MS:[M+H]=399
MS:[M+H]=472
MS:[M+H]=442
実施例21に記載されている手順と同様の手順を用いて、2-オキソ-1-ピリダジン-4-イルメチル-2,3-ジヒドロ-1H-ベンゾイミダゾール-5-スルホン酸イソプロピル(4-メトキシ-2-メチルフェニル)アミド(23mg;23%)を、白色固体の形態で得る。
Claims (12)
- 式(I)の化合物、並びに医薬として許容できるその付加塩、その水和物及び/又はその溶媒和物:
・Lは、単結合又はメチレン基CH2を表し、
・Xは、以下の環状基を表し:
・構成要素Q1、Q2及びQ3のうちの1つ若しくは2つは、窒素原子を表し、他の構成要素は、-CR2a基に相当し、又は構成要素Q1、Q2及びQ3のそれぞれは、-CR2a基に相当し、
・R1は、直鎖状又は分岐状C3〜C5アルキル基、C3〜C5シクロアルキル基、直鎖状又は分岐状C2〜C5アルケニル基、-CH2-(C3〜C5)シクロアルキル基、C4〜C5ヘテロシクロアルキル基、-CH2-(C4〜C6)ヘテロシクロアルキル基を表し、
・R2は、水素原子又はハロゲン原子、直鎖状又は分岐状C1〜C5アルキル基、直鎖状又は分岐状C2〜C4アルケニル基、C1〜C4アルコキシ基、シアノ基-CN、-C(=O)R'2基を表し、R'2は、C1〜C3アルコキシ基、-CF3基を表し;前記アルキル、アルケニル及びアルコキシ基は、場合により、1個又は複数のハロゲン原子で置換されており;
・R2aは、水素原子又はハロゲン原子、直鎖状又は分岐状C1〜C5アルキル基、直鎖状又は分岐状C2〜C4アルケニル基、C1〜C4アルコキシ基、-CN基、ヒドロキシル基-OH、-CH(R3a)OH基、カルボン酸基-COOH、カルバモイル基-CONR2cR2d、アミド基-NR2cCOR2d、-SO2R2c基、-SOR2c基、-S(=O)(=NH-R2c)基を表し、前記アルキル、アルケニル及びアルコキシ基は、場合により、1個又は複数のハロゲン原子で置換されており、
・R2c及びR2dは、同一であっても異なっていてもよく、水素原子又は直鎖状若しくは分岐状C1〜C5アルキル基を表し;
・R3aは、水素原子又は直鎖状若しくは分岐状C1〜C5アルキル基を表し;
・R3は、 (CHR6)n-(Z)o-(CHR'6)p-R7基を表し、
・n、o及びpは、同一であっても異なっていてもよく、0又は1から3の範囲の自然数を表し、
・Zは、メチレン基-CH2-、アミノ基-NH-及び酸素原子-O-から選択される二価基を表し、
・R6及びR'6は、同一であっても異なっていてもよく、水素原子、メチル基-CH3、-OH基、ヒドロキシメチル基、カルボン酸官能基-COOHを表し、
・R7は:
- R'7は(C1)アルキル(C6)ヘテロ環を表すCOOR'7基、
- 1個又は複数のハロゲン原子、1個又は複数の直鎖状又は分岐状C1〜C3アルキル基、1個又は複数の-OH基、1個又は複数のカルボニル官能基、1個又は複数の直鎖状又は分岐状C1〜C4ヒドロキシアルキル基、1個又は複数のアミノ基、1個又は複数の-C(=O)R7a基、1個又は複数のS(=O)2R7a基で任意選択で置換されている非カチオン性ヘテロシクロアルキル基であって、R7aが、直鎖状若しくは分岐状C1〜C3アルキル基、直鎖状若しくは分岐状C1〜C3アルコキシ基又はアミノ基N(R8a)(R8b)を表す、非カチオン性ヘテロシクロアルキル基、
- 1個若しくは複数のメチル基、1個若しくは複数のハロゲン原子、シアノ基-CN又は1個若しくは複数の-COR13基で任意選択で置換されている非カチオン性C3〜C6シクロアルキル基であって、R13が、直鎖状若しくは分岐状C1〜C3アルコキシ基又はヒドロキシル基を表す、非カチオン性C3〜C6シクロアルキル基、
- 1個若しくは複数のハロゲン原子、任意選択で、1個若しくは複数のハロゲン原子で置換されている1個若しくは複数の直鎖状若しくは分岐状C1〜C3アルキル基、1個若しくは複数のC1〜C3アルコキシ基、1個若しくは複数のアミノ基-NR11R12、1個若しくは複数の-COR11基、1個若しくは複数の-COOR11基、1個若しくは複数のアミド基-CONR11R12、1個若しくは複数の-SOR11基、1個若しくは複数の-SO2R11基、1個若しくは複数の-NHCOR11基、1個若しくは複数の-NHCOOR11基、1個若しくは複数の-SO2NR11R12基又は1個若しくは複数の-CN基で任意選択で置換されている芳香族若しくはヘテロ芳香族非カチオン性基であって、R11及びR12が、同一であっても異なっていてもよく、水素原子、ヒドロキシル基-OH、任意選択で、1個又は複数のハロゲン原子で置換されている直鎖状又は分岐状C1〜C3アルキル基を表す、芳香族若しくはヘテロ芳香族非カチオン性基
を表し、
・R5は、水素原子又はハロゲン原子、任意選択で、1個又は複数のハロゲン原子で置換されている直鎖状又は分岐状C1〜C3アルキル基;アミノ基-NH2、CH2R'7a基を表し、R'7aは、メトキシ基、ヒドロキシル基-OH、-CH2COOH基、-CH(R5b)OH基、カルボン酸基-COOH、-CN基、チオキソ官能基を表し、
・R5bは、水素原子;任意選択で、1個又は複数のカルボン酸官能基で置換されている直鎖状又は分岐状C1〜C3アルキル基;シクロプロピル基を表し、
・R8a及びR8bは、同一であっても異なっていてもよく、水素原子、直鎖状又は分岐状C1〜C3アルキル基又はシクロプロピル基を表す]。 - R7が、
式中:
- R7aが、直鎖状若しくは分岐状C1〜C3アルキル基、直鎖状若しくは分岐状C1〜C3アルコキシ基又はアミノ基N(R8a)(R8b)を表し、
- R8a及びR8bが、同一であっても異なっていてもよく、水素原子、直鎖状若しくは分岐状C1〜C3アルキル基又はシクロプロピル基を表し、
- R8及びR9が、同一であっても異なっていてもよく、水素原子、直鎖状若しくは分岐状C1〜C3アルキル基、ヒドロキシル基-OH、カルボニル官能基=O、(C1)ヒドロキシアルキル基(-CH2OH)、アミノ基NH2を表し、
- R8及びR9が、それらが結合している炭素原子と一緒になって、5-から7-員環の炭素環式環を形成できることを特徴とする、請求項1に記載の式(I)の化合物。 - R7が、
式中:
- R10が、水素原子若しくはハロゲン原子、任意選択で、1個若しくは複数のハロゲン原子で置換されている直鎖状若しくは分岐状C1〜C3アルキル基;C1〜C3アルコキシ基、アミノ基-NR11R12、-COR11基、-COOR11基、アミド基-CONR11R12、-SOR11基、-SO2R11基、-NHCOR11基、-NHCOOR11基、-SO2NR11R12基又は-CN基を表し;R11及びR12が、同一であっても異なっていてもよく、水素原子、又は任意選択で、1個若しくは複数のハロゲン原子で置換されている直鎖状若しくは分岐状C1〜C3アルキル基を表し、
mが、0又は1から3の範囲の自然数を表すことを特徴とする、請求項1に記載の式(I)の化合物。 - R1が、直鎖状若しくは分岐状C3〜C5アルキル基、又はC3〜C5シクロアルキル基を表すことを特徴とする、請求項1から4のいずれか一項に記載の式(I)の化合物。
- R5が、水素原子を表すことを特徴とする、請求項1から5のいずれか一項に記載の式(I)の化合物。
- 医薬としての、請求項1から7のいずれか一項に記載の化合物。
- 座瘡の処置におけるその使用のための、請求項1から8のいずれか一項に記載の化合物。
- 乾癬の処置におけるその使用のための、請求項1から8のいずれか一項に記載の化合物。
- 請求項1から7のいずれか一項に記載の、1つ又は複数の定義されている化合物を含む医薬組成物。
- 座瘡、アトピー性皮膚炎及び/又は乾癬の処置におけるその使用のための、請求項11に記載の、定義されている医薬組成物。
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PCT/EP2015/080691 WO2016097393A1 (fr) | 2014-12-19 | 2015-12-18 | Dérivés benzimidazoles sulfonamides en tant qu'agonistes inverses du récepteur gamma orphelin associé aux rétinoïdes ror gamma (t) |
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FR3063079B1 (fr) | 2017-02-17 | 2019-03-22 | Galderma Research & Development | Derives sulfonamides hydroxyles en tant qu'agonistes inverses du recepteur gamma orphelin associe aux retinoides ror gamma (t) |
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