JP2021500346A - Ret9及びvegfr2阻害剤 - Google Patents
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- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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Abstract
Description
本願は、2017年10月20日に提出された米国仮特許出願62/575,280の利益を主張し、参照によってその全体の内容が本明細書に組み入れられる。
(a)式Iの化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド若しくは同位体標識化合物又はそれらの薬学的に許容される塩と、
(b)その使用説明書と、
を含むキットが提供される。
(a)本明細書で提供される組成物と、
(b)その使用説明書と、
を含むキットが提供される。
(a)本明細書で提供される医薬組成物と、
(b)その使用説明書と、
を含むキットが提供される。
本開示を説明するために用いられるいくつかの用語の定義が以下に挙げられる。具体的な例で限定されない限り、これらの定義は、用語が本明細書及び特許請求の範囲全体で使用される場合にその用語に、個別に又はより大きな群の一部に適用される。
1つの観点において本明細書で提供されるのは式I:
1つの観点では、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を含む組成物である。
1つの観点では、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を含む医薬組成物である。
本明細書で提供されるのは、疾患を治療する化合物、粒子、被覆された粒子、及びその組成物である。いくつかの実施の形態では、対象の疾患を治療する方法が提供され、該方法は、治療を必要とする対象に本明細書で提供される有効量の化合物を投与することを含む。特定の実施の形態では、有効量は治療上有効量である。特定の実施の形態では、有効量は予防的な有効量である。特定の実施の形態では、対象は成長因子関連疾患を患っている。特定の実施の形態では、対象は成長因子関連疾患に感受性がある。特定の実施の形態では、対象はRET関連疾患を患っている。特定の実施の形態では、対象はRET関連疾患に感受性がある。特定の実施の形態では、対象は黄斑変性症の進行の危険を有する。
標的としてのDNAで標識された血管内皮増殖因子受容体2(VEGFR2)を用いて、固定化したアデノシン三リン酸(ATP)部位特異的リガンドの結合の競合における化合物の能力を評価するために競合結合アッセイ(DISCOVERX(商標) KINOMESCAN(商標))が用いられた。試験化合物の、固定化したリガンドと競合する能力がDNA標識の定量的ポリメラーゼ連鎖反応(qPCR)を用いて測定された(Fabian,M.A.et al.,23 Nature Biotechnology 329−336(2005);Karaman,M.W.et al.,26 Nature Biotechnology 127−132(2008))。
(付記1)
式I:
式I
付記1に記載の化合物。
付記1に記載の化合物。
付記1に記載の化合物。
式I
前記式Iの同位体標識化合物は、式Iの化合物又はその薬学的に許容される塩の重水素化誘導体である、
付記1に記載の化合物。
付記1から5のいずれか一つに記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物又はそれらの薬学的に許容される塩を含む、
組成物。
担体をさらに含む、
付記6に記載の組成物。
付記1から5のいずれか一つに記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物又はそれらの薬学的に許容される塩を含む、
医薬組成物。
薬学的に許容される担体をさらに含む、
付記8に記載の医薬組成物。
治療上有効量の付記1から5のいずれか一つに記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド若しくは同位体標識化合物又はそれら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における眼疾患の治療方法。
治療上有効量の付記6又は7に記載の組成物を対象に投与することを含む、
治療を必要とする対象における眼疾患の治療方法。
治療上有効量の付記8又は9に記載の医薬組成物を対象に投与することを含む、
治療を必要とする対象における眼疾患の治療方法。
前記眼疾患が網膜症である、
付記10から12のいずれか一つに記載の方法。
前記眼疾患が黄斑変性症である、
付記10から12のいずれか一つに記載の方法。
前記眼疾患が緑内障である、
付記10から12のいずれか一つに記載の方法。
前記眼疾患が角膜血管新生である、
付記10から12のいずれか一つに記載の方法。
前記化合物、前記組成物又は前記医薬組成物が対象の片眼又は両眼に送達される、
付記10から16のいずれか一つに記載の方法。
対象の眼への送達に適した、
付記6又は7に記載の組成物。
対象の眼への送達に適した、
付記8又は9に記載の医薬組成物。
治療上有効量の付記1から5のいずれか一つに記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物若しくはそれらの薬学的に許容される塩、治療上有効量の付記6若しくは7に記載の組成物、又は治療上有効量の付記8若しくは9に記載の医薬組成物を対象に投与することを含む、治療を必要とする対象における増殖性疾患、眼疾患、外皮疾患、炎症疾患、自己免疫疾患、自己炎症性疾患、又は代謝疾患の治療方法。
治療上有効量の付記1から5のいずれか一つに記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物若しくはそれらの薬学的に許容される塩、治療上有効量の付記6若しくは7に記載の組成物、又は治療上有効量の付記8若しくは9に記載の医薬組成物を対象に投与することを含む、
VEGFR2関連疾患の治療方法。
治療上有効量の付記1から5のいずれか一つに記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物若しくはそれらの薬学的に許容される塩、治療上有効量の付記6若しくは7に記載の組成物、又は治療上有効量の付記8若しくは9に記載の医薬組成物を対象に投与することを含む、
VEGFR2関連疾患の治療方法。
式(I)
式(X)
Xがハロゲンであって、
Rがアミン保護基である、
調製方法。
XがCl又はFである、
付記24に記載の方法。
Rがtert−ブチルオキシカルボニルである、
付記24に記載の方法。
式(X)
複数の粒子を含み、
前記粒子は、
付記1に記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド若しくは同位体標識化合物又は前記いずれかの薬学的に許容される塩を含むコア粒子と、
前記コア粒子の周囲の粘液浸透性促進表面改変物質の皮膜と、
を含む、
粘液浸透性医薬組成物。
前記粘液浸透性促進表面改変物質は、
(親水性ブロック)−(疎水性ブロック)−(親水性ブロック)構造の三元ブロック共重合体である、
付記28に記載の粘液浸透性医薬組成物。
前記三元ブロック共重合体は、
ポロキサマーである、
付記28に記載の粘液浸透性医薬組成物。
前記粘液浸透性促進表面改変物質は、前記コア粒子の外表面に、nm2あたり少なくとも0.01表面改変物質の密度で存在する、
付記28に記載の粘液浸透性医薬組成物。
治療上有効量の付記28に記載の粘液浸透性医薬組成物を対象に投与することを含む、
治療を必要とする対象における眼疾患の治療方法。
治療上有効量の付記28に記載の粘液浸透性医薬組成物を対象に投与することを含む、
治療を必要とする対象における増殖性疾患、眼疾患、皮膚疾患、炎症疾患、自己免疫疾患、自己炎症性疾患、又は代謝疾患の治療方法。
治療上有効量の付記28に記載の粘液浸透性医薬組成物を対象に投与することを含む、
VEGFR2関連疾患の治療方法。
眼疾患を治療するための付記34に記載の方法。
前記眼疾患が黄斑変性症である、
付記32又は35に記載の方法。
前記眼疾患が滲出加齢性黄斑変性症である、
付記32又は35に記載の方法。
Claims (36)
- 式I:
- 式I
請求項1に記載の化合物。 -
請求項1に記載の化合物。 -
請求項1に記載の化合物。 - 式I
前記式Iの同位体標識化合物は、式Iの化合物又はその薬学的に許容される塩の重水素化誘導体である、
請求項1に記載の化合物。 - 請求項1から5のいずれか一項に記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物又はそれらの薬学的に許容される塩を含む、
組成物。 - 担体をさらに含む、
請求項6に記載の組成物。 - 請求項1から5のいずれか一項に記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物又はそれらの薬学的に許容される塩を含む、
医薬組成物。 - 薬学的に許容される担体をさらに含む、
請求項8に記載の医薬組成物。 - 治療上有効量の請求項1から5のいずれか一項に記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド若しくは同位体標識化合物又はそれら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における眼疾患の治療方法。 - 治療上有効量の請求項6又は7に記載の組成物を対象に投与することを含む、
治療を必要とする対象における眼疾患の治療方法。 - 治療上有効量の請求項8又は9に記載の医薬組成物を対象に投与することを含む、
治療を必要とする対象における眼疾患の治療方法。 - 前記眼疾患が網膜症である、
請求項10から12のいずれか一項に記載の方法。 - 前記眼疾患が黄斑変性症である、
請求項10から12のいずれか一項に記載の方法。 - 前記眼疾患が緑内障である、
請求項10から12のいずれか一項に記載の方法。 - 前記眼疾患が角膜血管新生である、
請求項10から12のいずれか一項に記載の方法。 - 前記化合物、前記組成物又は前記医薬組成物が対象の片眼又は両眼に送達される、
請求項10から16のいずれか一項に記載の方法。 - 対象の眼への送達に適した、
請求項6又は7に記載の組成物。 - 対象の眼への送達に適した、
請求項8又は9に記載の医薬組成物。 - 治療上有効量の請求項1から5のいずれか一項に記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物若しくはそれらの薬学的に許容される塩、治療上有効量の請求項6若しくは7に記載の組成物、又は治療上有効量の請求項8若しくは9に記載の医薬組成物を対象に投与することを含む、治療を必要とする対象における増殖性疾患、眼疾患、外皮疾患、炎症疾患、自己免疫疾患、自己炎症性疾患、又は代謝疾患の治療方法。
- 治療上有効量の請求項1から5のいずれか一項に記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物若しくはそれらの薬学的に許容される塩、治療上有効量の請求項6若しくは7に記載の組成物、又は治療上有効量の請求項8若しくは9に記載の医薬組成物を対象に投与することを含む、
VEGFR2関連疾患の治療方法。 - 治療上有効量の請求項1から5のいずれか一項に記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド、同位体標識化合物若しくはそれらの薬学的に許容される塩、治療上有効量の請求項6若しくは7に記載の組成物、又は治療上有効量の請求項8若しくは9に記載の医薬組成物を対象に投与することを含む、
VEGFR2関連疾患の治療方法。 - 式(I)
式(X)
Xがハロゲンであって、
Rがアミン保護基である、
調製方法。 - XがCl又はFである、
請求項24に記載の方法。 - Rがtert−ブチルオキシカルボニルである、
請求項24に記載の方法。 - 式(X)
- 複数の粒子を含み、
前記粒子は、
請求項1に記載の化合物、その溶媒和物、水和物、多形物、共結晶、プロドラッグ、N−オキシド若しくは同位体標識化合物又は前記いずれかの薬学的に許容される塩を含むコア粒子と、
前記コア粒子の周囲の粘液浸透性促進表面改変物質の皮膜と、
を含む、
粘液浸透性医薬組成物。 - 前記粘液浸透性促進表面改変物質は、
(親水性ブロック)−(疎水性ブロック)−(親水性ブロック)構造の三元ブロック共重合体である、
請求項28に記載の粘液浸透性医薬組成物。 - 前記三元ブロック共重合体は、
ポロキサマーである、
請求項28に記載の粘液浸透性医薬組成物。 - 前記粘液浸透性促進表面改変物質は、前記コア粒子の外表面に、nm2あたり少なくとも0.01表面改変物質の密度で存在する、
請求項28に記載の粘液浸透性医薬組成物。 - 治療上有効量の請求項28に記載の粘液浸透性医薬組成物を対象に投与することを含む、
治療を必要とする対象における眼疾患の治療方法。 - 治療上有効量の請求項28に記載の粘液浸透性医薬組成物を対象に投与することを含む、
治療を必要とする対象における増殖性疾患、眼疾患、皮膚疾患、炎症疾患、自己免疫疾患、自己炎症性疾患、又は代謝疾患の治療方法。 - 治療上有効量の請求項28に記載の粘液浸透性医薬組成物を対象に投与することを含む、
VEGFR2関連疾患の治療方法。 - 眼疾患を治療するための請求項34に記載の方法。
- 前記眼疾患が黄斑変性症である、
請求項32又は35に記載の方法。 - 前記眼疾患が滲出加齢性黄斑変性症である、
請求項32又は35に記載の方法。
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