JP2022501327A - イミダゾキノリン化合物およびその使用 - Google Patents
イミダゾキノリン化合物およびその使用 Download PDFInfo
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- 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
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
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- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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Abstract
Description
本出願は、2018年9月7日に出願された米国仮特許出願第62/728,556号の利益を主張し、その全内容は参照により本明細書に組み込まれる。
ここで、
R1は、それぞれの存在において、独立して、F、Cl、Br、またはI;
R2は、−O−(C3−5シクロアルキル)、−O−(C1−3アルキル)、−O−(C1−3ハロアルキル)、−S−(C1−3アルキル)、−S(O)(C1−3アルキル)、または−S(O2)(C1−3アルキル);および
nは、0、1、2、3、または4である。
一態様では、本明細書で提供されるのは、イミダゾキノリン誘導体である化合物である。一実施形態では、前記化合物は、表1の化合物、またはその薬学的に許容される塩である。
ここで、
R1は、それぞれの存在において、独立して、F、Cl、Br、またはI;
R2は−O−(C3−5シクロアルキルl)、−O−(C1−3アルキル)、−O−(C1−3ハロアルキル)、−S−(C1−3アルキル)、−S(O)(C1−3アルキル)、または−S(O2)(C1−3アルキル);および
nは、0、1、2、3、または4である。
いくつかの実施形態において、R1はFである。いくつかの実施形態において、R1はHまたはFである。いくつかの実施形態において、R1はH(すなわちnは0である)である。いくつかの実施形態において、R1はH、F、Cl、Br、またはIである。
別の態様では、本明細書で提供されるのは、本明細書で提供される化合物(すなわち、表1の化合物またはその薬学的に許容される塩)を対象に投与することを含む、治療を必要とする対象の癌を治療する方法である。いくつかの実施形態では、癌はHER2陽性癌である。
以下に示す合成スキームでは、特に明記されていない限り、すべての温度を摂氏で示し、すべての部と百分率を重量で示す。試薬および溶媒を商業的供給業者から購入し、特に明記しない限り、更なる精製を行うとなく使用する。無水テトラヒドロフラン(THF)とN,N−ジメチルホルムアミド(DMF)を商業的供給元から購入し、受け取ったまま使用する。
HEK−Blue hTLR7細胞を3×104細胞/ウェルで播種し、9つの濃度の陽性対照(CL264)および3つの化合物(レシキモド、化合物2、化合物3)で処理した。HEK−Blue TLR7細胞は、TLR7刺激後のNF−κB活性化時における胎盤アルカリホスファターゼ(SEAP)の分泌により、TLR7の生物活性を測定するのに役立てることができる。陰性対照として水を使用した。5%CO2中37℃で約16時間の培養後、635nmで分光光度計を使用してSEAPを測定した。
HEK−Blue hTLR8細胞を3×104細胞/ウェルで播種し、9つの濃度の陽性対照(ssRNA40)および4つの試験品(レシキモド、化合物2、化合物3)で処理した。HEK−Blue hTLR8細胞は、TLR8刺激後のNF−κB活性化時における胎盤アルカリホスファターゼ(SEAP)の分泌により、TLR8の生物活性を測定するのに役立てることができる。陰性対照として水を使用した。5%CO2中37℃で約16時間の培養後、635nmで分光光度計を使用してSEAPを測定した。
(付記1)
式(I)の化合物:
(ここで、
R1は、それぞれの存在において、独立して、F、Cl、Br、またはI;
R2は、−O−(C3−5シクロアルキル)、−O−(C1−3ハロアルキル)、−S−(C1−3アルキル)、−S(O)(C1−3アルキル)、または−S(O2)(C1−3アルキル);および
nは、0、1、2、3、または4である。)
R1がF、Cl、Br、またはIである、付記1に記載の化合物。
R1がFである、付記1に記載の化合物。
R2が−O−(C3−5シクロアルキル)、−O−(C1−3モノハロアルキル)、−O−(C1−3ジハロアルキル)、−O−(C1−3トリハロアルキル)、−S−(C1−3アルキル)、−S(O)(C1−3アルキル)、または−S(O2)(C1−3アルキル)である、付記1に記載の化合物。
R2が、−O−CF3、−O−CH2−CF3、−O−シクロプロピル、−S−メチル、−S−エチル、−S(O)−メチル、−S(O)−エチル、−S(O2)−メチル、または−S(O2)−エチルである、付記1に記載の化合物。
nが0である、付記1に記載の化合物。
nが1である、付記1に記載の化合物。
nが2である、付記1に記載の化合物。
付記1から19のいずれか1項に記載の化合物を含む組成物。
付記1から19のいずれか1項に記載の化合物、またはその薬学的に許容される塩を含む医薬組成物。
付記1から19のいずれか1項に記載の化合物を治療を必要とする対象に投与することを含む、前記対象におけるウイルス感染を治療する方法。
前記ウイルス感染がC型肝炎ウイルス(HCV)感染を含む、付記22に記載の方法。
付記1から19のいずれか1項に記載の化合物を治療を必要とする対象に投与することを含む、前記対象の癌を治療する方法。
付記1から19のいずれか1項に記載の化合物を治療を必要とする対象に投与することを含む、前記対象におけるヒト上皮成長因子受容体2(HER2)陽性癌を治療する方法。
前記癌が食道、胃、結腸、直腸、膵臓、肺、***、子宮頸部、子宮体、卵巣、膀胱、頭頸部、子宮内膜、骨肉腫、前立腺、または神経芽細胞腫である、付記24または付記25に記載の方法。
付記1から19のいずれか1項に記載の化合物を治療を必要とする対象に投与することを含む、前記対象におけるアレルギー性疾患を治療する方法。
付記1から19のいずれか1項に記載の化合物、付記20に記載の組成物、または付記21に記載の医薬組成物の、ウイルス感染症、癌、またはアレルギー性疾患の治療のための医薬品の製造における、使用。
付記1から19のいずれか1項に記載の化合物を含む、治療を必要とする対象への投与に適した剤形。
付記1から19のいずれか1項に記載の化合物およびその使用説明書を含むキット。
Claims (30)
- R1がF、Cl、Br、またはIである、請求項1に記載の化合物。
- R1がFである、請求項1に記載の化合物。
- R2が−O−(C3−5シクロアルキル)、−O−(C1−3モノハロアルキル)、−O−(C1−3ジハロアルキル)、−O−(C1−3トリハロアルキル)、−S−(C1−3アルキル)、−S(O)(C1−3アルキル)、または−S(O2)(C1−3アルキル)である、請求項1に記載の化合物。
- R2が、−O−CF3、−O−CH2−CF3、−O−シクロプロピル、−S−メチル、−S−エチル、−S(O)−メチル、−S(O)−エチル、−S(O2)−メチル、または−S(O2)−エチルである、請求項1に記載の化合物。
- nが0である、請求項1に記載の化合物。
- nが1である、請求項1に記載の化合物。
- nが2である、請求項1に記載の化合物。
- 請求項1から19のいずれか1項に記載の化合物を含む組成物。
- 請求項1から19のいずれか1項に記載の化合物、またはその薬学的に許容される塩を含む医薬組成物。
- 請求項1から19のいずれか1項に記載の化合物を治療を必要とする対象に投与することを含む、前記対象におけるウイルス感染を治療する方法。
- 前記ウイルス感染がC型肝炎ウイルス(HCV)感染を含む、請求項22に記載の方法。
- 請求項1から19のいずれか1項に記載の化合物を治療を必要とする対象に投与することを含む、前記対象の癌を治療する方法。
- 請求項1から19のいずれか1項に記載の化合物を治療を必要とする対象に投与することを含む、前記対象におけるヒト上皮成長因子受容体2(HER2)陽性癌を治療する方法。
- 前記癌が食道、胃、結腸、直腸、膵臓、肺、***、子宮頸部、子宮体、卵巣、膀胱、頭頸部、子宮内膜、骨肉腫、前立腺、または神経芽細胞腫である、請求項24または請求項25に記載の方法。
- 請求項1から19のいずれか1項に記載の化合物を治療を必要とする対象に投与することを含む、前記対象におけるアレルギー性疾患を治療する方法。
- 請求項1から19のいずれか1項に記載の化合物、請求項20に記載の組成物、または請求項21に記載の医薬組成物の、ウイルス感染症、癌、またはアレルギー性疾患の治療のための医薬品の製造における、使用。
- 請求項1から19のいずれか1項に記載の化合物を含む、治療を必要とする対象への投与に適した剤形。
- 請求項1から19のいずれか1項に記載の化合物およびその使用説明書を含むキット。
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CN115350279A (zh) | 2016-01-07 | 2022-11-18 | 博笛生物科技有限公司 | 用于***的抗-her2组合 |
CN115554406A (zh) | 2016-01-07 | 2023-01-03 | 博笛生物科技有限公司 | 用于***的抗-cd20组合 |
CN115317603A (zh) | 2016-07-07 | 2022-11-11 | 小利兰·斯坦福大学托管委员会 | 抗体佐剂缀合物 |
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EP4306523A2 (en) | 2024-01-17 |
KR20210074290A (ko) | 2021-06-21 |
WO2020051356A1 (en) | 2020-03-12 |
AU2019335366A1 (en) | 2021-03-25 |
CN113164460A (zh) | 2021-07-23 |
EP3846807A4 (en) | 2022-05-18 |
EP3846807B1 (en) | 2023-08-02 |
US20210214354A1 (en) | 2021-07-15 |
EP4306523A3 (en) | 2024-01-24 |
CA3111786A1 (en) | 2020-03-12 |
EP3846807A1 (en) | 2021-07-14 |
ES2963112T3 (es) | 2024-03-25 |
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