JP2022542162A - ヘテロ環式アミド化合物及びその製造方法並びに使用 - Google Patents
ヘテロ環式アミド化合物及びその製造方法並びに使用 Download PDFInfo
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Abstract
Description
L1は、-O-、-NH-及び単結合から選ばれ、
R1は、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R2、R3は、それぞれ独立して、H、
L2は、単結合、-O-、-S-、-NH-及び-NHC(=O)-から選ばれ、
R4は、
環Aは、4~10員のヘテロシクロアルキル基及びC3-10シクロアルキル基から選ばれ、
nは、0、1、2、3、4、5及び6から選ばれ、
mは、1、2、3、4、5及び6から選ばれ、
R5は、それぞれ独立して、ハロゲン、N3、OH、SH、NH2、CN、
L3は、-O-、-S-、-NH-及び-CH2-から選ばれ、
R6、R7は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
R9、R12は、それぞれ独立して、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R10、R11、R13、R14は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN及びC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
もしくは、R9はR13に結合され、3~7個の炭素原子を含む炭素鎖が形成され、
Tは、N又はCHから選ばれ、
Rは、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
R’は、H、F、Cl、Br、I、OH、NH2及びCH3から選ばれ、
前記5~6員のヘテロシクロアルキル基、5~6員のヘテロアリール基、5~10員のヘテロシクロアルキル基又は5~10員のヘテロアリール基は、独立して-O-、-NH-、-S-及びNから選ばれた1つ、2つ又は3つのヘテロ原子又はヘテロ原子団を含む。
L1は、-O-、-NH-及び単結合から選ばれ、
R1は、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R2、R3は、それぞれ独立して、H、
L2は、単結合、-O-、-S-、-NH-及び-NHC(=O)-から選ばれ、
R4は、
環Aは、5~10員のヘテロシクロアルキル基及びC3-10シクロアルキル基から選ばれ、
nは、0、1、2、3、4、5及び6から選ばれ、
mは、1、2、3、4、5及び6から選ばれ、
R5は、それぞれ独立して、ハロゲン、N3、OH、SH、NH2、CN、
L3は、-O-、-S-、-NH-及び-CH2-から選ばれ、
R6、R7は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
R9は、それぞれ独立して、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R13は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN及びC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
もしくは、R9はR13に結合され、3~7個の炭素原子を含む炭素鎖が形成され、
Rは、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
R’は、H、F、Cl、Br、I、OH、NH2及びCH3から選ばれ、
前記5~6員のヘテロシクロアルキル基、5~6員のヘテロアリール基、5~10員のヘテロシクロアルキル基又は5~10員のヘテロアリール基は、独立して-O-、-NH-、-S-及びNから選ばれた1つ、2つ又は3つのヘテロ原子又はヘテロ原子団を含む。
L1は、-O-、-NH-及び単結合から選ばれ、
R1は、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R2、R3は、それぞれ独立して、H、
L2は、単結合、-O-、-S-、-NH-及び-NHC(=O)-から選ばれ、
R4は、
環Aは、5~10員のヘテロシクロアルキル基及びC3-10シクロアルキル基から選ばれ、
nは、0、1、2、3、4、5及び6から選ばれ、
mは、1、2、3、4、5及び6から選ばれ、
R5は、それぞれ独立して、ハロゲン、N3、OH、SH、NH2、CN、
L3は、-O-、-S-、-NH-及び-CH2-から選ばれ、
R6、R7は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
Rは、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
R’は、H、F、Cl、Br、I、OH、NH2及びCH3から選ばれ、
前記5~6員のヘテロシクロアルキル基、5~6員のヘテロアリール基、5~10員のヘテロシクロアルキル基又は5~10員のヘテロアリール基は、独立して-O-、-NH-、-S-及びNから選ばれた1つ、2つ又は3つのヘテロ原子又はヘテロ原子団を含む。
特に明記されていない限り、本明細書で使用される以下の用語及びフレーズは、以下の意味を持つことを意図する。特定の用語又はフレーズは、特定の定義なしに不確定又は不明確であると見なされるべきではなく、通常の意味で理解されるべきである。本明細書に商品名が記載されている場合、対応する商品又はその活性成分を指すことを意図する。
ステップ1:化合物1-2の製造
1H NMR(400MHz、DMSO-d6)δ8.15(s、1H)、7.99(s、1H)、7.73~7.70(m、1H)、7.51(s、1H)、7.30(s、1H)、5.49(s、2H)、4.05(s、2H)、3.98(s、3H)、3.44(s、2H)、1.31(s、9H)。
1H NMR(400MHz、DMSO-d6)δ12.83(br s、2H)、7.97(br s、2H)、7.64(d、J=5.6Hz、2H)、7.36(br d、J=8.4Hz、2H)、7.32(br d、J=5.2Hz、2H)、7.25~6.91(m、2H)、6.52(s、2H)、5.82(br d、J=4.0Hz、2H)、4.92(br d、J=10.2Hz、4H)、4.65(d、J=3.6Hz、1H)、4.52(br d、J=7.2Hz、4H)、4.08(br s、2H)、3.75(s、3H)、3.27(br d、J=8.0Hz、2H)、3.18(s、4H)、3.11~2.92(m、3H)、2.11(d、J=1.6Hz、6H)。
1H NMR(400MHz、DMSO-d6)δ8.51(s、0.3H)、7.59(s、1H)、7.56(s、1H)、7.30(s、1H)、7.27(s、1H)、6.59(s、1H)、6.56(s、1H)、5.86~5.83(m、2H)、5.04~5.00(m、4H)、4.62~4.56(m、4H)、4.21~4.20(m、2H)、4.05~4.02(m、2H)、3.76(s、1H)、3.52~3.51(m、4H)、2.20(s、3H)、2.19(s、3H)、2.07~2.05(m、1H)、1.97~1.94(m、1H)、1.36~1.31(m、6H)、0.96~0.94(m、3H)、0.92~0.90(m、3H)。
1H NMR(400MHz、Chloroform-d)δ7.76(d、J=1.8Hz、1H)、7.67(d、J=1.9Hz、1H)、7.14(d、J=2.2Hz、1H)、4.73(s、1H)、4.47(dd、J=7.6、4.3Hz、1H)、4.31(td、J=6.2、1.7Hz、2H)、4.09~3.94(m、3H)、3.87~3.76(m、2H)、3.71(d、J=4.3Hz、1H)、3.30(s、3H)、2.18~2.13(m、2H)、2.01(s、1H)、1.51~1.41(m、1H)、1.40~1.21(m、4H)、1.11~0.96(m、28H)。
1H NMR(400MHz、DMSO-d6)δ12.79(s、2H)、7.96(s、2H)、7.63(dd、J=3.5、1.2Hz、2H)、7.39~7.22(m、4H)、6.50(s、2H)、5.87~5.76(m、2H)、4.91(dd、J=10.1、4.2Hz、4H)、4.79(d、J=6.8Hz、1H)、4.69(d、J=1.6Hz、1H)、4.62(t、J=5.6Hz、1H)、4.51(q、J=7.1Hz、4H)、4.08(t、J=6.4Hz、2H)、3.93(q、J=5.6Hz、1H)、3.77~3.71(m、4H)、3.67~3.43(m、5H)、3.19(s、3H)、2.10(d、J=1.3Hz、6H)、1.82~1.81(m、2H)、1.26(t、J=7.1Hz、6H)。
1H NMR(400MHz、DMSO-d6)δ12.81(s、2H)、7.95(s、2H)、7.66~7.61(m、2H)、7.33(s、2H)、7.26(d、J=9.9Hz、2H)、6.56(s、1H)、6.51(s、1H)、5.80(s、2H)、4.94~4.91(s、6H)、4.62~4.61(m、1H)、4.58~4.43(m、5H)、3.99(s、2H)、3.90(t、J=6.3Hz、2H)、3.63~3.60(m、2H)、3.46~3.44(m、5H)、3.17~3.15(m、2H)、3.15~2.54(m、3H)、2.54~2.11(m、11H)、1.73~1.53(m、5H)、1.32-1.26(m、6H)。
1H NMR(400MHz、CDCl3)δ6.59(s、1H)、4.53~4.49(m、2H)、4.39~4.22(m、2H)、2.26(s、3H)、1.47~1.28(m、6H)。
1H NMR(400MHz、CDCl3)δ4.53(q、J=7.2Hz、2H)、4.40(q、J=7.2Hz、2H)、2.28(s、3H)、1.66~1.38(m、6H)。
1H NMR(400MHz、CDCl3)δ11.26(br s、1H)、8.23~7.95(m、5H)、7.91(s、1H)、6.00(s、2H)、2.98(s、3H)。
1H NMR(400MHz、CDCl3)δ7.50~7.31(m、5H)、6.66(s、1H)、5.31(s、2H)、4.59(t、J=7.2Hz、2H)、2.27(s、3H)、2.21~2.19(m、2H)、2.08~1.95(m、2H)、1.96(t、J=2.4Hz、1H)。
1H NMR(400MHz、CDCl3)δ7.50~7.33(m、5H)、6.66(s、1H)、5.29(s、2H)、4.64(t、J=7.2Hz、2H)、4.55~4.43(m、2H)、4.37(q、J=7.2Hz、2H)、2.48(t、J=7.2Hz、2H)、2.28(s、3H)、2.26(s、3H)、2.14(q、J=7.2Hz、2H)、1.40~1.37(m、6H)。
1H NMR(400MHz、CDCl3)δ6.70(s、1H)、4.50(q、J=7.2Hz、4H)、4.34(q、J=7.2Hz、2H)、2.60(br t、J=7.6Hz、2H)、2.30(s、3H)、2.20(s、3H)、1.85(q、J=7.2Hz、2H)、1.58~1.44(m、2H)、1.40~1.34(m、8H)。
1H NMR(400MHz、DMSO-d6)δ12.89(s、2H)、7.99(s、2H)、7.66(d、J=1.3Hz、2H)、7.45~7.24(m、4H)、6.50(s、1H)、5.68~5.66(m、2H)、4.96~4.81(m、6H)、4.64~4.63(m、3H)、4.46~4.42(m、3H)、3.99(s、2H)、3.48~3.41(m、3H)、3.17(s、3H)、3.08~2.95(m、2H)、2.71~2.69(m、2H)、2.16(s、3H)、2.08(s、3H)、1.76~1.74(m、6H)、1.49~1.47(m、4H)、1.33~1.27(m、6H)。
1H NMR(400MHz、DMSO-d6)δ8.72(br s、4H)、8.13(br s、2H)、7.56~7.51(m、2H)、7.44~7.34(m、4H)、5.98~5.69(m、2H)、5.03~4.81(m、4H)、4.17~4.08(m、2H)、3.82~3.71(m、5H)、0.84~0.76(m、9H)、-0.01~-0.08(m、6H)。
1H NMR(400MHz、CD3OD)δ8.53(s、1H)、7.59(s、1H)、7.52(s、1H)、7.27(s、1H)、7.23(s、1H)、6.61(s、1H)、6.53(s、1H)、5.89~5.78(m、2H)、5.02~4.95(m、4H)、4.66~4.51(m、4H)、4.03~3.90(m、2H)、3.73(s、3H)、3.29~3.20(m、2H)、3.18~3.10(m、1H)、3.00(d、J=12.0Hz、1H)、2.52~2.35(m、3H)、2.34~2.25(m、1H)、2.21(s、3H)、2.18(s、3H)、2.16~1.98(m、2H)、1.90~1.69(m、2H)、1.61~1.39(m、4H)、1.39~1.27(m、6H)。
1H NMR(400MHz、CD3OD-d4)δ8.46(s、1H)、7.59(s、1H)、7.56(s、1H)、7.27(s、1H)、7.20(s、1H)、6.61(s、1H)、6.56(s、1H)、5.81(s、2H)、4.99(s、4H)、4.68(s、4H)、4.66~4.54(m、4H)、3.96~3.80(m、2H)、3.71(s、3H)、3.46(s、4H)、2.63~2.48(m、2H)、2.21(s、3H)、2.19(s、3H)、1.64~1.49(m、2H)、1.41~1.23(m、6H)。
蛍光偏光アッセイ(fluorescence polarization assay、FP assay)は、ヒトSTINGタンパク質に対する化合物の親和性を検出するために使用される。反応系にはフルオレセインにより標識された一定量のc-di-GMP及び様々な濃度の試験化合物がある。組換えヒトSTINGのC末端タンパク質を加える場合、2つの小分子がタンパク質と競合的に結合される。フルオレセインにより標識された結合状態のc-di-GMPは液相でゆっくりと回転し、この時に検出された蛍光偏光度も高くなる。蛍光偏光度は、試験化合物の濃度及び親和性に反比例する。反応系の偏光の大きさを検出することにより、ヒトSTINGに対する試験化合物の親和性を正確に把握することができる。
実験で使用されたTHP1-DualTM細胞(InvivoGen目次コード:thpd-nfis)は、2つの誘導性レポーター遺伝子をヒト単球細胞株THP1に安定的に結合することによって構築された。分泌型胚性アルカリホスファターゼ(SEAP)レポーター遺伝子のプロモーター配列組成は、1つのIFN-βの基本プロモーター、上流の5つのNF-κB共発現転写応答エレメント(NF-κB consensus transcriptional response element)のコピー及び3つのc-Rel結合部位のコピーを含む。分泌されたルシフェラーゼ(Lucia)レポーター遺伝子は、5つのインターフェロン刺激応答エレメント(interferon(IFN)-stimulated response elements)及び1つのISG54の基本プロモーターによって駆動された。それにより、SEAPの活性を検出することによってNF KBを研究する経路とLuciaルシフェラーゼの活性を評価することによってIRFを研究する経路の、STINGの2つの主な下流信号伝達経路を同時に研究することが可能になる。
この実験では、CT-26結腸癌同系マウスモデルによって化合物の有効性を評価する。3E5個のCT-26結腸癌細胞(ATCC-CRL-2638)を6~8週齢のBalb/Cマウス(上海霊暢生物)皮下に接種し、腫瘍体積が100mm3に達した時にランダムに群分けを行い、各群に6匹がある。群分け後の1日目に腫瘍内投与を行った。化合物1の各群の投与量はそれぞれ、マウスあたり1μg、マウスあたり0.1μg、マウスあたり0.01μgである。投与後、週に3回で腫瘍体積を測定した。腫瘍体積の計算式:V=0.5a×b2、aとbはそれぞれ、腫瘍の長径と短径を表す。各点は腫瘍体積の平均値及び標準誤差(SEM)である。対照群(生理食塩水)と投与群との違いは、two-way ANOVAによって統計的に分析した(15日目の統計的差は、例えば、Prism8、****p<0.0001)。
R’は、H、F、Cl、Br、I、OH、NH2及びCH3から選ばれ、
前記5~6員のヘテロシクロアルキル基、5~6員のヘテロアリール基、4~10員のヘテロシクロアルキル基又は5~10員のヘテロアリール基は、独立して-O-、-NH-、-S-及びNから選ばれた1つ、2つ又は3つのヘテロ原子又はヘテロ原子団を含む。
Claims (35)
- 式(IA)に示される化合物、その光学異性体及びその薬学的に許容される塩。
(ただし、
L1は、-O-、-NH-及び単結合から選ばれ、
R1は、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R2、R3は、それぞれ独立して、H、
C3-6シクロアルキル基、5~6員のヘテロシクロアルキル基及び5~6員のヘテロアリール基から選ばれ、前記C3-6シクロアルキル基、5~6員のヘテロシクロアルキル基又は5~6員のヘテロアリール基は、任意選択で1つ、2つ又は3つのRで置換され、
L2は、単結合、-O-、-S-、-NH-及び-NHC(=O)-から選ばれ、
R4は、
及びC1-6アルキル-C(=O)-から選ばれ、前記C1-6アルキル-C(=O)-は、任意選択で1つ、2つ又は3つのRで置換され、
環Aは、4~10員のヘテロシクロアルキル基及びC3-10シクロアルキル基から選ばれ、
nは、0、1、2、3、4、5及び6から選ばれ、
mは、1、2、3、4、5及び6から選ばれ、
R5は、それぞれ独立して、ハロゲン、N3、OH、SH、NH2、CN、
C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基、C1-6アルキルアミノ基及び5~6員のヘテロシクロアルキル-L3-から選ばれ、前記C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基又はC1-6アルキルアミノ基は、任意選択で1つ、2つ又は3つのRで置換され、前記5~6員のヘテロシクロアルキル-L3-は、任意選択で1つ、2つ、3つ又は4つのRで置換され、
L3は、-O-、-S-、-NH-及び-CH2-から選ばれ、
R6、R7は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基及びC1-6アルキルアミノ基から選ばれ、前記C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基又はC1-6アルキルアミノ基は、任意選択で1つ、2つ又は3つのRで置換され、
R8は、H、ハロゲン、N3、OH、SH、NH2、CN、
及びC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
もしくは、R3はR8に連結され、一つの5~6員のヘテロ環を形成し、
R9、R12は、それぞれ独立して、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R10、R11、R13、R14は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN及びC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
もしくは、R9はR13に結連結され、一つの3~7個の炭素原子を含む炭素鎖がを形成し、
Tは、N又はCHから選ばれ、
Rは、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基、C1-6アルキルアミノ基、5~6員のヘテロシクロアルキル基、フェニル基及び5~10員のヘテロアリール基から選ばれ、前記C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基、C1-6アルキルアミノ基、5~6員のヘテロシクロアルキル基、フェニル基又は5~10員のヘテロアリール基は、任意選択で1つ、2つ又は3つのR’で置換され、
R’は、H、F、Cl、Br、I、OH、NH2及びCH3から選ばれ、
前記5~6員のヘテロシクロアルキル基、5~6員のヘテロアリール基、5~10員のヘテロシクロアルキル基又は5~10員のヘテロアリール基は、独立して-O-、-NH-、-S-及びNから選ばれた1つ、2つ又は3つのヘテロ原子又はヘテロ原子団を含む。) - 下記から選ばれる請求項1に記載の化合物、その光学異性体及びその薬学的に許容される塩。
(ただし、
L1は、-O-、-NH-及び単結合から選ばれ、
R1は、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R2、R3は、それぞれ独立して、H、
C3-6シクロアルキル基、5~6員のヘテロシクロアルキル基及び5~6員のヘテロアリール基から選ばれ、前記C3-6シクロアルキル基、5~6員のヘテロシクロアルキル基又は5~6員のヘテロアリール基は、任意選択で1つ、2つ又は3つのRで置換され、
L2は、単結合、-O-、-S-、-NH-及び-NHC(=O)-から選ばれ、
R4は、
及びC1-6アルキル-C(=O)-から選ばれ、前記C1-6アルキル-C(=O)-は、任意選択で1つ、2つ又は3つのRで置換され、
環Aは、5~10員のヘテロシクロアルキル基及びC3-10シクロアルキル基から選ばれ、
nは、0、1、2、3、4、5及び6から選ばれ、
mは、1、2、3、4、5及び6から選ばれ、
R5は、それぞれ独立して、ハロゲン、N3、OH、SH、NH2、CN、
C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基、C1-6アルキルアミノ基及び5~6員のヘテロシクロアルキル-L3-から選ばれ、前記C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基、C1-6アルキルアミノ基は、任意選択で1つ、2つ又は3つのRで置換され、前記5~6員のヘテロシクロアルキル-L3-は、任意選択で1つ、2つ、3つ又は4つのRで置換され、
L3は、-O-、-S-、-NH-及び-CH2-から選ばれ、
R6、R7は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基及びC1-6アルキルアミノ基から選ばれ、前記C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基又はC1-6アルキルアミノ基は、任意選択で1つ、2つ又は3つのRで置換され、
R9は、それぞれ独立して、HとC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
R13は、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN及びC1-6アルキル基から選ばれ、前記C1-6アルキル基は、任意選択で1つ、2つ又は3つのRで置換され、
もしくは、R9はR13に連結され、一つの3~7個の炭素原子を含む炭素鎖を形成し、
Rは、それぞれ独立して、H、ハロゲン、N3、OH、SH、NH2、CN、
C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基、C1-6アルキルアミノ基、5~6員のヘテロシクロアルキル基、フェニル基及び5~10員のヘテロアリール基から選ばれ、前記C1-6アルキル基、C1-6アルコキシ基、C1-6アルキルチオ基、C1-6アルキルアミノ基、5~6員のヘテロシクロアルキル基、フェニル基又は5~10員のヘテロアリール基は、任意選択で1つ、2つ又は3つのR’で置換され、
R’は、H、F、Cl、Br、I、OH、NH2及びCH3から選ばれ、
前記5~6員のヘテロシクロアルキル基、5~6員のヘテロアリール基、5~10員のヘテロシクロアルキル基又は5~10員のヘテロアリール基は、独立して-O-、-NH-、-S-及びNから選ばれた1つ、2つ又は3つのヘテロ原子又はヘテロ原子団を含む。) - 環Aは、テトラヒドロ-2H-ピラニル基、テトラヒドロフラニル基、モルホリニル基、2,7-ジアザスピロ[4.5]デシル基及び2-オキサ6-アザスピロ[3.3]ヘプタニル基から選ばれる、請求項1又は2に記載の化合物、その光学異性体及びその薬学的に許容される塩。
- 請求項1~16のいずれか1項に記載の化合物又はその薬学的に許容される塩を含む薬物組成物。
- 前記薬物組成物は、1つ又は複数の薬学的に許容される担体、希釈剤又は賦形剤をさらに含む、請求項17に記載の薬物組成物。
- STING媒介性疾患の予防又は治療における、請求項1~16のいずれか1項に記載の化合物又は薬学的に許容される塩、又は、請求項17又は18に記載の薬物組成物の使用。
- 前記STING媒介性疾患は、癌、炎症、感染性疾患又は免疫関連疾患を含む、請求項19に記載の使用。
- 前記癌は、副腎皮質癌、肛門癌、肛門直腸癌、肛門管癌、虫垂癌、小脳星状細胞腫、脳星状細胞腫、基底細胞癌、皮膚癌(非黒色腫)、胆道癌、肝外胆管癌、肝内胆管癌、膀胱癌、骨関節癌、骨肉腫、悪性線維性組織球腫、脳癌、脳腫瘍、脳幹神経膠腫、上衣腫、髄芽腫、視覚経路及び視床下部神経膠腫、乳癌、気管支腺腫、神経系癌、神経系リンパ腫、中枢神経系癌、中枢神経系リンパ腫、子宮頸癌、慢性リンパ性白血病、慢性骨髄性白血病、慢性骨髄増殖性疾患、結腸癌、結腸直腸癌、皮膚T細胞リンパ腫、リンパ腫、菌状息肉腫、セザリー症候群、子宮内膜癌、食道癌、頭蓋外胚細胞腫瘍、性腺外胚細胞腫瘍、眼癌、眼内黒色腫、網膜芽細胞腫、胆嚢癌、胃癌、消化管カルチノイド、消化管間質腫瘍(GIST)、胚細胞腫瘍、卵巣胚細胞腫瘍、頭頸部癌、肝細胞癌、ホジキンリンパ腫、膵島細胞腫瘍、カポシ肉腫、腎臓癌、喉癌、急性リンパ芽球性白血病、急性骨髄性白血病、毛細胞白血病、唇及び口腔癌、肝癌、肺癌、非小細胞肺癌、小細胞肺癌、非ホジキンリンパ腫、原発性中枢神経系リンパ腫、ワルデンシュトレームマクログロブリン血症、黒色腫瘍、中皮腫、転移性扁平上皮癌、舌癌、多発性内分泌腺腫症候群、骨髄異形成症候群、多発性骨髄腫、鼻咽頭癌、神経芽細胞腫、口腔咽頭癌、卵巣癌、卵巣上皮癌、卵巣低悪性度腫瘍、膵臓癌、膵島細胞膵臓癌、副鼻腔及び鼻腔癌、副甲状腺癌、陰茎癌、咽頭癌、褐色細胞腫、松果体腫瘍、下垂体腫、形質細胞腫瘍、胸膜肺芽腫、前立腺癌、直腸癌、腎骨盤及び尿管移行上皮癌、網膜芽細胞腫、横紋筋肉腫、唾液腺癌、ユーイングファミリー肉腫、カポジ肉腫、滑膜肉腫、子宮癌、子宮肉腫、小腸癌、軟部肉腫、扁平上皮癌、テント上原始神経外胚葉性腫瘍、精巣癌、喉癌、胸腺腫、尿道癌、子宮内膜症、膣癌、外陰癌、悪性胸水又はウィルムス腫瘍から選ばれる、請求項20に記載の使用。
- 、前記STING媒介性疾患は、頭頸部癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、乳癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、結腸直腸癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、黒色腫から選ばれる、請求項19に記載の使用。
- 、前記STING媒介性疾患は、リンパ癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、膀胱癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、皮膚扁平上皮癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、卵巣癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、胃癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、食道癌から選ばれる、請求項19に記載の使用。
- 前記STING媒介性疾患は、前立腺癌から選ばれる、請求項19に記載の使用。
- STING媒介性腫瘍合併症の予防又は治療における、請求項1~16のいずれか1項に記載の化合物又は薬学的に許容される塩、又は、請求項17又は18に記載の薬物組成物の使用。
- 前記STING媒介性腫瘍合併症は、悪性胸水から選ばれる、請求項33に記載の使用。
- 前記STING媒介性腫瘍合併症は、腹水から選ばれる、請求項33に記載の使用。
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