JP2019536760A - 縮合二環ピリジン化合物、及びampa受容体調節因子としてのそれらの使用 - Google Patents
縮合二環ピリジン化合物、及びampa受容体調節因子としてのそれらの使用 Download PDFInfo
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- JP2019536760A JP2019536760A JP2019522295A JP2019522295A JP2019536760A JP 2019536760 A JP2019536760 A JP 2019536760A JP 2019522295 A JP2019522295 A JP 2019522295A JP 2019522295 A JP2019522295 A JP 2019522295A JP 2019536760 A JP2019536760 A JP 2019536760A
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- trifluoromethyl
- triazolo
- pyridine
- methyl
- chloro
- Prior art date
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- 108090000078 AMPA Receptors Proteins 0.000 title claims description 74
- -1 bicyclic pyridine compounds Chemical class 0.000 title claims description 65
- 150000001875 compounds Chemical class 0.000 claims abstract description 608
- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 238000000034 method Methods 0.000 claims abstract description 54
- 239000012453 solvate Substances 0.000 claims abstract description 33
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 63
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 57
- 238000011282 treatment Methods 0.000 claims description 45
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 36
- 230000000694 effects Effects 0.000 claims description 36
- 201000010099 disease Diseases 0.000 claims description 35
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 208000035475 disorder Diseases 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 24
- 230000001404 mediated effect Effects 0.000 claims description 19
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 15
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Classifications
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Abstract
Description
本出願は、2016年10月26日に出願された米国特許出願第62/412,868号の優先権を主張するものであり、その内容は参照により本明細書に組み込まれる。
本発明は、AMPA受容体調節特性を有する化合物、これらの化合物を含む医薬組成物、これらの化合物を調製するための化学プロセス、及び動物、特にヒトにおけるAMPA受容体活性に関連する疾患の治療におけるその使用に関する。
Yは、N又はCHであり、
R1は、H、ハロ及びC1〜6アルキルからなる群から選択され、
R2は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ及びC3〜8シクロアルキルからなる群から選択され、
R3は、H、ハロ、C1〜6アルキル、C1〜6アルコキシ、CN及びCF3からなる群から選択され、
R4は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ、Fで置換されたフェニル、及びピリジルからなる群から選択され、
Yは、N又はCHであり、
R1は、H、ハロ及びC1〜6アルキルからなる群から選択され、
R2は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ及びC3〜8シクロアルキルからなる群から選択され、
R3は、H、ハロ、C1〜6アルキル、C1〜6アルコキシ、CN及びCF3からなる群から選択され、
R4は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ、Fで置換されたフェニル、及びピリジルからなる群から選択され、
R1は、H、ハロ、CH3及びCH2CH3からなる群から選択され、
R2は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ及びC3〜8シクロアルキルからなる群から選択され、
R4は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ、Fで置換されたフェニル、及びピリジルからなる群から選択され、
R5は、
(A)有効量の式(I):
Yは、N又はCHであり、
R1は、H、ハロ及びC1〜6アルキルからなる群から選択され、
R2は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ及びC3〜8シクロアルキルからなる群から選択され、
R3は、H、ハロ、C1〜6アルキル、C1〜6アルコキシ、CN及びCF3からなる群から選択され、
R4は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ、Fで置換されたフェニル、及びピリジルからなる群から選択され、
式(I)の化合物の製薬的に許容される塩、N−オキシド、又は溶媒和物、の少なくとも1つと、
(B)少なくとも1つの製薬的に許容される賦形剤と、を含む医薬組成物である。
Yは、N又はCHであり、
R1は、H、ハロ及びC1〜6アルキルからなる群から選択され、
R2は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ及びC3〜8シクロアルキルからなる群から選択され、
R3は、H、ハロ、C1〜6アルキル、C1〜6アルコキシ、CN及びCF3からなる群から選択され、
R4は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ、Fで置換されたフェニル、及びピリジルからなる群から選択され、
その製薬的に許容される塩、N−オキシド、又は溶媒和物、の少なくとも1つを、それを必要としている対象に投与することを含む、方法である。
本明細書で使用するとき、「含む(including)」、「含有する(containing)」、及び「含む(comprising)」という用語は、本明細書では幅広い非限定的意味で用いられる。
表3.本明細書で使用される略語及び頭字語としては、以下が挙げられる。
次に、本発明の方法において有用な例示的な化合物を、以下のその一般的調製についての例示的な合成スキーム及び以下の具体例を参照することによって説明する。
又は
Inertsil ODS−3カラム(3μm、30×100mm、T=45℃)を使用してShimadzu LC−8AシリーズHPLC上で行い、80mL/分の流速で、5% ACN/H2O(いずれも0.05% TFAを含む)の移動相を1分間保持してから5〜99%のACN勾配を6分間かけて送液した後、99% ACNで3分間保持した。
又は
XBridge C18 OBDカラム(5μm、50×100mm)を使用してShimadzu LC−8AシリーズHPLC上で行い、80mL/分の流速で、5% ACN/H2O(いずれも0.05% TFAを含む)の移動相を1分間保持してから5〜99%のACN勾配を14分間かけて送液した後、99% ACNで10分間保持した。
又は
XBridge C18カラム(5μm、100×50mm)を使用してGilson HPLC上で行い、80mL/分の流速で、5〜99% ACN/20mM NH4OHの移動相を10分間かけて送液した後、99% ACNで2分間保持した。
7−クロロ−6−(ジフルオロメチル)−4−メチル−2−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−3−カルボン酸(1.80g、5.48mmol)のジメチルスルホキシド(18mL)溶液に、炭酸銀(453mg、1.64mmol)及び酢酸(47μL、0.821mmol)を添加した。反応混合物を120℃で1時間撹拌した。反応混合物をジエチルエーテル(100mL)で希釈し、混合物を食塩水で洗浄した(50mL×10回)。有機層を硫酸マグネシウムで乾燥させ、濾過し、蒸発させた。精製(FCC、SiO2、n−ペンタン:ジエチルエーテル(4:1))して、白色結晶性固体として標題化合物(1.30g、4.56mmol、83%)を得た。1H NMR(300MHz,DMSO−d6)δ 7.59(s,1H),7.57−7.52(m,1H),7.44(t,J=53.7Hz,1H),2.62(s,3H)。
6−ヨード−8−メチル−2−プロピル−[1,2,4]トリアゾロ[1,5−a]ピリジン。1,2−ジアミノ−5−ヨード−3−メチルピリジン−1−イウム2,4,6−トリメチルベンゼンスルホネート(中間体12)(500mg、1.11mmol)のAcOH(13.1mL)溶液に、Cu(OAc)2(101mg、0.56mmol)及びブチルアルデヒド(0.3mL、3.34mmol)を添加した。混合物を18時間で70℃まで加熱し、次いで、室温まで冷却した。更なるCu(OAc)2(0.5当量)を加え、反応物を更に4.5時間かけて70℃まで加熱した。室温まで冷却した後、混合物を濾過し、濾液を減圧下で濃縮した。残渣をEtOAcに溶解して、飽和NaHCO3水溶液で洗浄した。水層をEtOAcで抽出し(2回)、合わせた有機物を食塩水で洗浄し、Na2SO4で乾燥させ、濾過した。濾液を減圧下で濃縮した。精製(FCC、SiO2;0〜50% EtOAc/ヘキサン)して、標題化合物(195mg、58%)を得た。MS(ESI):C10H12IN3の質量計算値、301.0;m/z実測値、302.0[M+H]+。
6−ヨード−8−メチル−2−プロピル−[1,2,4]トリアゾロ[1,5−a]ピリジン。1,2−ジアミノ−5−ヨード−3−メチルピリジン−1−イウム2,4,6−トリメチルベンゼンスルホネート(中間体12)(500mg、1.11mmol)の酪酸(1.6mL)溶液に、酪酸無水物(0.55mL、3.34mmol)を添加した。反応物をマイクロ波反応器内で180℃で30分間撹拌した後、EtOAc及びH2Oで希釈した。次いで、混合物を4N NaOHで中和し、水層をEtOAcで2回抽出し、合わせた有機物を食塩水で洗浄し、Na2SO4で乾燥させ、濾過した。濾液を減圧下で濃縮した。精製(FCC、SiO2;0〜50% EtOAc/ヘキサン)して、白色固体として標題化合物(269mg、80%)を得た。
方法A:中間体66の方法Aに類似する様式で、1,2−ジアミノ−3−メチル−5−(トリフルオロメチル)ピリジン−1−イウム2,4,6−トリメチルベンゼンスルホネート(中間体59)を使用して、標題化合物を調製した。MS(ESI):C11H12F3N3の質量計算値、243.1;m/z実測値、244.2[M+H]+。
中間体32に類似する様式で、2−シクロプロピル−6−ヨード−8−メチル−[1,2,4]トリアゾロ[1,5−a]ピリジンを用い、標題化合物を調製した。MS(ESI):C11H10F3N3の質量計算値、241.2;m/z実測値、242.1[M+H]+。1H NMR(500MHz,DMSO−d6)δ 9.32(dt,J=2.0,1.0Hz,1H),7.80−7.62(m,1H),2.54(t,J=0.9Hz,3H),2.24−2.15(m,1H),1.11−1.06(m,2H),1.03−0.98(m,2H)。
カルシウム流入アッセイ
このアッセイを用いて、TARP γ8依存性AMPA受容体活性を阻害する化合物の能力を試験した。AMPA受容体は、グルタミン酸塩によって活性化される非選択的カチオンチャネルである。イオンチャネル型グルタミン酸受容体は、通常、急速に脱感作しすぎるため、FLIPRアッセイにおいて検出可能なカルシウム流入が不可能である(Strange et al.(2006).「Functional characterisation of homomeric ionotropic glutamate receptors GluR1−GluR6 in a fluorescence−based high throughput screening assay.」Comb Chem High Throughput Screen 9(2):147〜158)。しかし、この脱感作は不完全であり、かなりの量の定常状態電流が、グルタミン酸塩の持続的存在下に残っている(Cho et al.(2007).「Two families of TARP isoforms that have distinct effects on the kinetic properties of AMPA receptors and synaptic currents.」Neuron 55(6):890〜904)。
Claims (29)
- 式(I)の化合物:
[式中、
Yは、N又はCHであり、
R1は、H、ハロ及びC1〜6アルキルからなる群から選択され、
R2は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ及びC3〜8シクロアルキルからなる群から選択され、
R3は、H、ハロ、C1〜6アルキル、C1〜6アルコキシ、CN及びCF3からなる群から選択され、
R4は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ、Fで置換されたフェニル、及びピリジルからなる群から選択され、
は、−CH=N−、−CH2−C(=O)−及び−S−C(=O)−からなる群から選択される]及び
その製薬的に許容される塩、N−オキシド、又は溶媒和物。 - YがNである、請求項1に記載の化合物。
- YがCHである、請求項1に記載の化合物。
- R1がHである、請求項1に記載の化合物。
- R1が、Cl又はFである、請求項1に記載の化合物。
- R1が、CH3又はCH2CH3である、請求項1に記載の化合物。
- R2が、CF3、CHF2又はCF2(CH3)である、請求項1に記載の化合物。
- R2が、CH3、CH2CH3、CH2CH2CH3又はCH(CH3)2である、請求項1に記載の化合物。
- R2が、シクロプロピルである、請求項1に記載の化合物。
- R2が、OCH3又はOCH2CH3である、請求項1に記載の化合物。
- R3が、H、Cl、CH3又はCH2CH3である、請求項1に記載の化合物。
- R3が、OCH3又はCNである、請求項1に記載の化合物。
- R3が、CF3である、請求項1に記載の化合物。
- R4が、CF3、CF2(CH3)又はCHF2である、請求項1に記載の化合物。
- R4が、OCH3である、請求項1に記載の化合物。
- R4が、CH2CH3である、請求項1に記載の化合物。
- R4が、4−フルオロフェニル、ピリジン−3−イル、又はピリジン−4−イルである、請求項1に記載の化合物。
- 以下からなる群から選択される化合物:
5−(7−クロロ−1H−インダゾール−5−イル)−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−メチル−1H−インダゾール−5−イル)−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−クロロインドリン−2−オン、
5−(2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メチルインドリン−2−オン、
8−クロロ−5−(7−クロロ−1H−インダゾール−5−イル)−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−8−メチル−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−(ジフルオロメチル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−メチル−1H−インダゾール−5−イル)−2−(ジフルオロメチル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(2−(ジフルオロメチル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
7−メチル−5−(2−(ジフルオロメチル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
2−(ジフルオロメチル)−6−(トリフルオロメチル)−5−(7−(トリフルオロメチル)−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(2−(ジフルオロメチル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メトキシインドリン−2−オン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−(ジフルオロメチル)−6−メトキシ−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−(ジフルオロメチル)−6−メトキシ−5−(7−メチル−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−(ジフルオロメチル)−6−メトキシ−5−(7−(トリフルオロメチル)−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−6−(ジフルオロメチル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−(ジフルオロメチル)−5−(7−メチル−1H−インダゾール−5−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(6−(ジフルオロメチル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
5−[6−(ジフルオロメチル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル]−7−メチル−インドリン−2−オン、
5−[6−(ジフルオロメチル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル]−7−メトキシ−インドリン−2−オン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−メチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(2−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
7−メチル−5−(2−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−エチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−エチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(2−エチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
5−(2−エチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メチルインドリン−2−オン、
8−クロロ−5−(7−クロロ−1H−インダゾール−5−イル)−2−エチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
8−クロロ−2−エチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−エチル−8−フルオロ−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−[2−エチル−8−フルオロ−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル]インドリン−2−オン、
2−シクロプロピル−8−フルオロ−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−8−フルオロ−2−イソプロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−エチル−8−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−イソプロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−イソプロピル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−シクロプロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−シクロプロピル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(2−シクロプロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
5−(2−シクロプロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メチルインドリン−2−オン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−(1,1−ジフルオロエチル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−メトキシ−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−6−(ジフルオロメチル)−2−エチル−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−(ジフルオロメチル)−2−エチル−5−(7−メチル−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(6−(ジフルオロメチル)−2−エチル−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
5−(6−(ジフルオロメチル)−2−エチル−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メチルインドリン−2−オン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−シクロプロピル−6−(ジフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−シクロプロピル−6−(ジフルオロメチル)−5−(7−メチル−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−6−メトキシ−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−メトキシ−5−(7−メチル−1H−インダゾール−5−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−エチル−5−(7−メチル−1H−インダゾール−5−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−6−(1,1−ジフルオロエチル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−(2−ジフルオロメチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)ベンゾ[d]チアゾール−2(3H)−オン、
6−(4−フルオロフェニル)−5−(7−メチル−1H−インダゾール−5−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−(4−フルオロフェニル)−5−(1H−インダゾール−5−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(6−(4−フルオロフェニル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メチルインドリン−2−オン、
5−(7−メチル−1H−インダゾール−5−イル)−6−(ピリジン−3−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−メチル−1H−インダゾール−5−イル)−6−(ピリジン−4−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−(4−フルオロフェニル)−2−メチル−5−(7−メチル−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−エチル−6−(4−フルオロフェニル)−5−(7−メチル−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−シクロプロピル−6−(4−フルオロフェニル)−5−(7−メチル−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(2,6−ビス(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−クロロ−1H−インダゾール、
5−(2,6−ビス(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−メチル−1H−インダゾール、
5−(2,6−ビス(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−メチルインドリン−2−オン、
5−(2,6−ビス(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−クロロインドリン−2−オン、
5−(2−シクロプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−メチルインドリン−2−オン、
5−(2−シクロプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−クロロインドリン−2−オン、
5−(2−シクロプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−メチル−1H−インダゾール、
7−クロロ−5−(2−シクロプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−1H−インダゾール、
5−(2−イソプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−メチルインドリン−2−オン、
5−(2−イソプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−クロロインドリン−2−オン、
7−クロロ−5−(2−イソプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−1H−インダゾール、及び
5−(2−イソプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−7−メチル−1H−インダゾール、並びに
その製薬的に許容される塩、N−オキシド、又は溶媒和物。 - 以下からなる群から選択される化合物:
7−クロロ−5−(2−シクロプロピル−8−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
2−シクロプロピル−8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−6−(ジフルオロメチル)−8−メチル−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−(ジフルオロメチル)−8−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−(ジフルオロメチル)−8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−(ジフルオロメチル)−8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−シクロプロピル−8−エチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−シクロプロピル−8−エチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(2−シクロプロピル−8−エチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メチルインドリン−2−オン、
5−(7−クロロ−1H−インダゾール−5−イル)−8−メチル−2−プロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−2−プロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−メチル−5−(8−メチル−2−プロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
2−(ジフルオロメチル)−8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−(ジフルオロメチル)−8−エチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−(ジフルオロメチル)−8−エチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2,8−ジエチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2,8−ジエチル−5−(7−メチル−1H−インダゾール−5−イル)−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−6−(ジフルオロメチル)−8−エチル−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−(ジフルオロメチル)−8−エチル−5−(7−メチル−1H−インダゾール−5−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−シクロプロピル−6−(ジフルオロメチル)−8−エチル−[1,2,4]トリアゾロ[1,5−a]ピリジン、
2−シクロプロピル−6−(ジフルオロメチル)−8−エチル−5−(7−メチル−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
6−(ジフルオロメチル)−8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−2−プロピル−[1,2,4]トリアゾロ[1,5−a]ピリジン、
8−クロロ−5−(7−クロロ−1H−インダゾール−5−イル)−2−プロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(8−クロロ−2−プロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
5−(8−クロロ−2−プロピル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メチルインドリン−2−オン、
5−(2−シクロプロピル−8−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−メチルインドリン−2−オン、
7−クロロ−5−(2−エチル−8−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
2−エチル−8−メチル−6−(トリフルオロメチル)−5−(7−(トリフルオロメチル)−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(2−エチル−8−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−7−(トリフルオロメチル)インドリン−2−オン、
7−クロロ−5−(2−エチル−8−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
7−エチル−5−(8−メチル−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
7−メチル−5−(8−メチル−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
7−メトキシ−5−(8−メチル−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(8−メチル−2,6−ビス(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)−2−オキソインドリン−7−カルボニトリル、
5−(7−クロロ−1H−インダゾール−5−イル)−6−(ジフルオロメチル)−8−メチル−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(6−(ジフルオロメチル)−8−メチル−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
6−(ジフルオロメチル)−8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−2−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−シクロプロピル−6−(ジフルオロメチル)−8−メチル−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(2−シクロプロピル−6−(ジフルオロメチル)−8−メチル−[1,2,4]トリアゾロ[1,5−a]ピリジン−5−イル)インドリン−2−オン、
2−シクロプロピル−6−(ジフルオロメチル)−8−メチル−5−(7−メチル−1H−インダゾール−5−イル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−6−(ジフルオロメチル)−2−エチル−8−メチル−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2,8−ジメチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
5−(7−クロロ−1H−インダゾール−5−イル)−2−エトキシ−8−メチル−6−(トリフルオロメチル)−[1,2,4]トリアゾロ[1,5−a]ピリジン、
7−クロロ−5−(2−シクロプロピル−6−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル)−1H−インダゾール、
5−[6−(ジフルオロメチル)−2−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル]−7−メチル−インドリン−2−オン、
7−(7−クロロ−1H−インダゾール−5−イル)−6−(ジフルオロメチル)−2−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン、
6−(ジフルオロメチル)−7−(7−メチル−1H−インダゾール−5−イル)−2−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン、
5−[6−(ジフルオロメチル)−4−メチル−2−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル]−7−メチル−インドリン−2−オン、
6−(ジフルオロメチル)−4−メチル−7−(7−メチル−1H−インダゾール−5−イル)−2−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン、
7−クロロ−5−[6−(ジフルオロメチル)−4−メチル−2−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン−7−イル]インドリン−2−オン、及び
7−(7−クロロ−1H−インダゾール−5−イル)−6−(ジフルオロメチル)−4−メチル−2−(トリフルオロメチル)ピラゾロ[1,5−a]ピリジン、並びに
その製薬的に許容される塩、N−オキシド、又は溶媒和物。 - 医薬組成物であって、
(A)有効量の式(I):
[式中、
Yは、N又はCHであり、
R1は、H、ハロ、C1〜6アルキルからなる群から選択され、
R2は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ及びC3〜8シクロアルキルからなる群から選択され、
R3は、H、ハロ、C1〜6アルキル、C1〜6アルコキシ、CN及びCF3からなる群から選択され、
R4は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ、Fで置換されたフェニル、及びピリジルからなる群から選択され、
は、−CH=N−、−CH2−C(=O)−及び−S−C(=O)−からなる群から選択される]
の化合物、及び式(I)の化合物の製薬的に許容される塩、N−オキシド、又は溶媒和物、の少なくとも1つと、
(B)少なくとも1つの製薬的に許容される賦形剤と、を含む、医薬組成物。 - 有効量の請求項23に記載の少なくとも1つの化合物と、少なくとも1つの製薬的に許容される賦形剤とを含む医薬組成物。
- AMPA受容体活性によって媒介される疾患、障害若しくは医学的状態に罹患しているか又はこれらの疾患、障害若しくは医学的状態であると診断された対象を治療する方法であって、このような治療を必要としている対象に、有効量の式(I):
[式中、
Yは、N又はCHであり、
R1は、H、ハロ、C1〜6アルキルからなる群から選択され、
R2は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ及びC3〜8シクロアルキルからなる群から選択され、
R3は、H、ハロ、C1〜6アルキル、C1〜6アルコキシ、CN及びCF3からなる群から選択され、
R4は、C1〜6アルキル、C1〜6ハロアルキル、C1〜6アルコキシ、Fで置換されたフェニル、及びピリジルからなる群から選択され、
は、−CH=N−、−CH2−C(=O)−及び−S−C(=O)−からなる群から選択される]
の化合物、及び式(I)の化合物の製薬的に許容される塩、N−オキシド又は溶媒和物、の少なくとも1つを投与することを含む、方法。 - 前記AMPA受容体によって媒介される疾患、障害又は医学的状態が、脳虚血、頭部外傷、脊髄損傷、アルツハイマー病、パーキンソン病、筋萎縮性側索硬化症(ALS)、ハンチントン舞踏病、AIDS神経障害、てんかん、精神障害、運動障害、疼痛、痙性、食品毒による神経障害、各種神経変性疾患、各種精神病、慢性疼痛、片頭痛、癌性疼痛、糖尿病性神経障害、脳炎、急性播種性脳脊髄炎、急性脱髄性多発神経障害(ギランバレー症候群)、慢性炎症性脱髄性多発神経炎、多発性硬化症、マルキアファーヴァビニャミ病、橋中心髄鞘崩壊症、デビック症候群、バロー病、HIV−又はHTLV−脊髄症、進行性多巣性白質脳症、二次性脱髄障害(例えば、CNSループスエリテマトーデス、結節性多発性動脈炎、シェーグレン症候群、サルコイドーシス、孤立性脳血管炎など)、統合失調症、前駆期統合失調症、認知障害、うつ病、不安障害、不安うつ病及び双極性障害から選択される、請求項27に記載の方法。
- 前記AMPA受容体によって媒介される疾患、障害又は状態が、うつ病、心的外傷後ストレス障害、てんかん、統合失調症、前駆期統合失調症又は認知障害である、請求項27に記載の方法。
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008113795A1 (en) * | 2007-03-20 | 2008-09-25 | Glaxo Group Limited | Compounds which potentiate ampa receptor and uses thereof in medicine |
WO2010066658A1 (en) * | 2008-12-09 | 2010-06-17 | Glaxo Group Limited | Compounds which potentiate the ampa receptor and uses thereof in medicine |
WO2011036889A1 (ja) * | 2009-09-25 | 2011-03-31 | 武田薬品工業株式会社 | 複素環化合物 |
JP2012502029A (ja) * | 2008-09-08 | 2012-01-26 | シグナル ファーマシューティカルズ,エルエルシー | アミノトリアゾロピリジン及びそのキナーゼ阻害剤としての使用 |
JP2012526735A (ja) * | 2009-05-12 | 2012-11-01 | ジャンセン ファーマシューティカルズ, インコーポレイテッド. | 1,2,4−トリアゾロ[4,3−a]ピリジン誘導体およびmGluR2受容体の正のアロステリック調節因子としてのその使用 |
WO2015183673A1 (en) * | 2014-05-28 | 2015-12-03 | Eli Lilly And Company | 6-substituted-3h-1,3-benzothiazol-2-one compounds as tarp-gamma 8 dependent ampa receptor antagonists |
JP2016501219A (ja) * | 2012-11-27 | 2016-01-18 | イーライ リリー アンド カンパニー | Tarp−ガンマ8依存性ampa受容体アンタゴニストとしての6−((s)−1−{1−[5−(2−ヒドロキシ−エトキシ)−ピリジン−2−イル]−1h−ピラゾール−3−イル}−エチル)−3h−1,3−ベンゾチアゾール−2−オン |
JP2019532981A (ja) * | 2016-10-26 | 2019-11-14 | ヤンセン ファーマシューティカ エヌ.ベー. | 融合アザヘテロ環状化合物、及びampa受容体調節因子としてのそれらの使用 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1100504A2 (en) | 1998-07-02 | 2001-05-23 | Eisai Co., Ltd. | Pharmaceutical compositions and their uses for treatment of demyelinating disorders |
AU2005271669A1 (en) * | 2004-08-03 | 2006-02-16 | Merck & Co., Inc. | 1,3-disubstituted heteroaryl NMDA/NR2B antagonists |
GB0719803D0 (en) * | 2007-10-10 | 2007-11-21 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
JP5498392B2 (ja) * | 2007-11-30 | 2014-05-21 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 1,5−ジヒドロ−ピラゾロ[3,4−d]ピリミジン−4−オン誘導体及びcns障害の治療のためのpde9aモジュレーターとしてのそれらの使用 |
JO3041B1 (ar) * | 2008-07-25 | 2016-09-05 | Galapagos Nv | مركبات جديدة مفيدة لمعالجة الأمراض التنكسية والالتهابية |
-
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Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008113795A1 (en) * | 2007-03-20 | 2008-09-25 | Glaxo Group Limited | Compounds which potentiate ampa receptor and uses thereof in medicine |
JP2012502029A (ja) * | 2008-09-08 | 2012-01-26 | シグナル ファーマシューティカルズ,エルエルシー | アミノトリアゾロピリジン及びそのキナーゼ阻害剤としての使用 |
WO2010066658A1 (en) * | 2008-12-09 | 2010-06-17 | Glaxo Group Limited | Compounds which potentiate the ampa receptor and uses thereof in medicine |
JP2012526735A (ja) * | 2009-05-12 | 2012-11-01 | ジャンセン ファーマシューティカルズ, インコーポレイテッド. | 1,2,4−トリアゾロ[4,3−a]ピリジン誘導体およびmGluR2受容体の正のアロステリック調節因子としてのその使用 |
WO2011036889A1 (ja) * | 2009-09-25 | 2011-03-31 | 武田薬品工業株式会社 | 複素環化合物 |
JP2016501219A (ja) * | 2012-11-27 | 2016-01-18 | イーライ リリー アンド カンパニー | Tarp−ガンマ8依存性ampa受容体アンタゴニストとしての6−((s)−1−{1−[5−(2−ヒドロキシ−エトキシ)−ピリジン−2−イル]−1h−ピラゾール−3−イル}−エチル)−3h−1,3−ベンゾチアゾール−2−オン |
WO2015183673A1 (en) * | 2014-05-28 | 2015-12-03 | Eli Lilly And Company | 6-substituted-3h-1,3-benzothiazol-2-one compounds as tarp-gamma 8 dependent ampa receptor antagonists |
JP2019532981A (ja) * | 2016-10-26 | 2019-11-14 | ヤンセン ファーマシューティカ エヌ.ベー. | 融合アザヘテロ環状化合物、及びampa受容体調節因子としてのそれらの使用 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019532981A (ja) * | 2016-10-26 | 2019-11-14 | ヤンセン ファーマシューティカ エヌ.ベー. | 融合アザヘテロ環状化合物、及びampa受容体調節因子としてのそれらの使用 |
JP6994029B2 (ja) | 2016-10-26 | 2022-01-14 | ヤンセン ファーマシューティカ エヌ.ベー. | 融合アザヘテロ環状化合物、及びampa受容体調節因子としてのそれらの使用 |
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