JP2013501730A - 脂質付加オキソアデニン誘導体 - Google Patents
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- SKZSOVJFNKAZFH-UHFFFAOYSA-N CCCCCCCCCCCCCCCC(OCC(COP(NCCN1CCC(C[n](c2n3)c(O)nc2c(N)nc3OCCCC)CC1)(O)=O)OC(CCCCCCCCCCCCCCC)=O)=O Chemical compound CCCCCCCCCCCCCCCC(OCC(COP(NCCN1CCC(C[n](c2n3)c(O)nc2c(N)nc3OCCCC)CC1)(O)=O)OC(CCCCCCCCCCCCCCC)=O)=O SKZSOVJFNKAZFH-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
R1=C1〜6アルキル、C1〜6アルキルアミノ、C1〜6アルコキシ、C3〜6シクロアルキルC1〜6アルキル、C3〜6シクロアルキルC1〜6アルキルアミノ、C3〜6シクロアルキルC1〜6アルコキシ、C1〜6アルコキシC1〜6アルキル、C1〜6アルコキシC1〜6アルキルアミノ、C1〜6アルコキシC1〜6アルコキシ;及び任意で、ヒドロキシル、アミノ、チオ、ヒドラジノ、ヒドラジド、アジド、アセチルエニル、カルボキシル又はマレイミドの基によって末端置換されたもの;
n=0〜6
Hetは、4員環、5員環又は6員環の置換された窒素複素環であり、式中、
X、Y=CH又はN、且つXとYの少なくとも一方が窒素原子であり、
Q=O、NH又は共有結合、
Z=O、CH2、CF2又は共有結合、
W=O、S
m=0〜6
p=1又は2
q=0又は1
A=
R2=H又は飽和若しくは不飽和のC4〜C24アルキル若しくはアシル
R3=飽和又は不飽和のC4〜C24アルキル又はアシル。
R1=C1〜6アルキル、C1〜6アルキルアミノ、C1〜6アルコキシ、C3〜6シクロアルキルC1〜6アルキル、C3〜6シクロアルキルC1〜6アルキルアミノ、C3〜6シクロアルキルC1〜6アルコキシ、C1〜6アルコキシC1〜6アルキル、C1〜6アルコキシC1〜6アルキルアミノ、C1〜6アルコキシC1〜6アルコキシ;分枝鎖又は非分枝鎖;
n=0〜6、
X=CH又はN、
Q=O、NH、又は共有結合、
Z=O、CH2、CF2又は共有結合、
W=O、S
m=0〜6
p=1又は2
q=0又は1
R2=H又は飽和若しくは不飽和のC4〜C24アルキル若しくはアシル
R3=飽和又は不飽和のC4〜C24アルキル又はアシル。
R1は、C1〜6アルキル、C1〜6アルキルアミノ、C1〜6アルコキシ、C1〜6アルコキシC1〜6アルキルアミノ、C1〜6アルコキシC1〜6アルコキシから成る群から選択され;
nは、0〜2であり、
Xは、CH又はNであり、
Qは、O、NH又は共有結合であり、
mは、0〜2であり、
qは、0であり、
R2は、H又は飽和若しくは不飽和のC4〜C24アルキル若しくはアシルであり、
R3は、飽和又は不飽和のC4〜C24アルキル又はアシルである。
式中、
R1は、C1〜6アルコキシであり、
nは、0〜2であり、
Xは、CH又はNであり、
Qは、O、NHであり、
mは、0〜2であり、
qは、0であり、
R2は、H又は飽和若しくは不飽和のC4〜C24アルキル若しくはアシルであり、
R3は、飽和又は不飽和のC4〜C24アルキル又はアシルである。
6−アミノ−2−ブトキシ−9−[N−(2−(1,2−ジパルミトイル−sn−グリセロ−3−ホスホ)エチル)−4−ピペリジニルメチル]−8−ヒドロキシプリン(化合物(II)、R1=n−ブトキシ、n=1、X=CH、Q=O、Z=O、W=O、m=2、p=1、R1=R2=n−C15H31CO)の調製
(5)ピリジン(6.4mL)中の上記(4)で調製した化合物(51mg)とホスホン酸水素1,2−ジパルミトイル−sn−グリセリル(93mg、化合物V1、R1=R2=パルミトイル)の溶液を塩化ピバロイル(0.047mL)で処理し、得られた反応混合物を室温で6時間撹拌した。次いでピリジン/水中のヨウ素(129mg)の溶液を加え、反応混合物を室温で1時間撹拌し、CHCl3で希釈し、次いで1MのNa2S2O5によって反応を止めた。水性層をCHCl3で2回抽出し、合わせた有機層を1Mのホウ酸トリエチルアンモニウム(pH8)で洗浄した。有機層を乾燥させ(Na2SO4)、濃縮した。CHCl3−MeOH−Et3N(勾配溶出90:10:1→75:25:1)によるシリカゲルでのフラッシュクロマトグラフィによって、白っぽい固形物として38mg(30%)の6−アミノ−2−ブトキシ−9−[N−(2−(1,2−ジパルミトイル−sn−グリセロ−3−ホスホ)エチル)−4−ピペリジニルメチル]−8−ヒドロキシプリンを得た。1H−NMR(CDCl3−CD3OD,400MHz):δ5.17(bs,1H),4.32(dd,1H),4.20−4.09(m,5H),3.98(brt,2H),3.69(br d,3H),3.23(br s,1H),1.86(br s,4H),1.69(m,2H),1.53(br s,4H),1.42(dd,2H),1.20(m,48H),0.91(t,3H),0.83(t,6H);HRMS[M−H]−C52H94N6O10P:計算値993.6768,観察値993.6782。
6−アミノ−2−ブトキシ−9−[N−(2−(1,2−ジパルミトイル−sn−グリセロ−3−ホスホルアミド)エチル)−4−ピペリジニルメチル]−8−ヒドロキシプリン(化合物(II)、R1=n−ブトキシ、n=1、X=CH、Q=NH、Z=O、W=O、m=2、p=1、R1=R2=n−C15H31CO)の調製
6−アミノ−2−ブトキシ−9−[1−(1,2−ジパルミトイル−sn−グリセロ−3−ホスホルアミド)−4−ピペラジニルエチル]−8−ヒドロキシプリン(化合物(II)、R1=n−ブトキシ、n=2、X=N、Q=単結合、Z=O、W=O、m=0、p=1、R1=R2=n−C15H31CO)の調製
クロロホルム中10mg/mLの脂質付加TLR7−LA1を10.4mL、丸底ガラスバイアルに移した。このバイアルに100mg/mLでクロロホルムに可溶化したDPPCを18.4mL加えた。5mg/mLでクロロホルムに可溶化した脂質付加TLR7−L化合物A3を丸底ガラスバイアルに移した。このバイアルに100mg/mLでクロロホルムに可溶化したDPPCを20mL加えた。穏やかな減圧下でBuchi Rotavaporにてクロロホルムを蒸発させた。真空下のデシケータにて少なくとも一晩、得られた膜をさらに乾燥させた。その後、事前に60℃に加熱した50mMのPO4−100mMのNaCl(pH7)の緩衝液を用いて軌道振盪器(最大速度:250rpm)にて脂質膜をゆっくり水和した。
脂質付加分子A3及びA1を生体内で評価した。表1に要約したSIV−p27含有の製剤を用いて6〜8週齢のC57BL/6メスのマウス(10匹/群)にワクチン接種した。マウスは、14日間離して2回、50μLの筋肉内注射を受け、以下に示すように初回と追加の後、様々な時点で採血した。
Claims (12)
- 式(I)の構造を有する化合物:
R1は、C1〜6アルキル、C1〜6アルキルアミノ、C1〜6アルコキシ、C3〜6シクロアルキルC1〜6アルキル、C3〜6シクロアルキルC1〜6アルキルアミノ、C3〜6シクロアルキルC1〜6アルコキシ、C1〜6アルコキシC1〜6アルキル、C1〜6アルコキシC1〜6アルキルアミノ、C1〜6アルコキシC1〜6アルコキシから成る群から選択され、任意に、ヒドロキシル、アミノ、チオ、ヒドラジノ、ヒドラジド、アジド、アセチレニル、カルボキシル又はマレイミドの基によって末端置換され、
nは、0又は1〜6の整数であり、
Hetは、4員環、5員環又は6員環の飽和複素環であり、式中、
X、Yは、CH又はN、且つXとYの少なくとも一方が窒素原子であり、
Qは、O、NH又は共有結合であり、
Zは、O、CH2、CF2又は共有結合であり、
Wは、O、Sであり、
mは、0又は1〜6の整数であり、
pは、1又は2の整数であり、
qは、0又は整数1であり、
Aは、
R2は、H又は直鎖、分枝鎖若しくは不飽和のC4〜C24アルキル若しくはアシルであり、
R3は、直鎖、分枝鎖又は不飽和のC4〜C24アルキル又はアシルである)、又は薬学上許容可能なその塩。 - 式IIの構造を有する化合物:
R1は、C1〜6アルキル、C1〜6アルキルアミノ、C1〜6アルコキシ、C3〜6シクロアルキルC1〜6アルキル、C3〜6シクロアルキルC1〜6アルキルアミノ、C3〜6シクロアルキルC1〜6アルコキシ、C1〜6アルコキシC1〜6アルキル、C1〜6アルコキシC1〜6アルキルアミノ、C1〜6アルコキシC1〜6アルコキシから成る群から選択され、
nは、0又は1〜6の整数であり、
Xは、CH又はNであり、
Qは、O、NH、又は共有結合であり、
Zは、O、CH2、CF2又は共有結合であり、
Wは、O、Sであり;
mは、0又は1〜6の整数であり、
pは、1又は2の整数であり、
qは、0又は整数1であり、
R2は、H又は直鎖、分枝鎖若しくは不飽和のC4〜C24アルキル若しくはアシルであり、
R3は、直鎖、分枝鎖又は不飽和のC4〜C24アルキル又はアシルである)、又は薬学上許容可能なその塩。 - R1が、C1〜6アルコキシ、又はC1〜6アルコキシC1〜6アルキルであり、
Qが、O,NHであり、
mが、0又は1〜2の整数であり、
qが、0であり、
R2が、H又は直鎖、分枝鎖若しくは不飽和のC4〜C24アルキル若しくはアシルであり、
R3が、直鎖、分枝鎖又は不飽和のC4〜C24アルキル又はアシルである、請求項3の化合物、又は薬学上許容可能なその塩。 - 請求項1〜8のいずれか1項に記載の化合物を投与することを含む、哺乳類で自然免疫の応答を誘導する方法。
- 前記応答が1型IFNを誘導することを含む請求項9に記載の方法。
- 前記応答が、炎症誘発性サイトカインを増大することを含む請求項9に記載の方法。
- 自然免疫の応答を誘導する方法、1型IFNの応答を誘導する方法、又は炎症誘発性サイトカインを増大する方法にて使用するための請求項1〜8のいずれか1項に記載の化合物。
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US23213209P | 2009-08-07 | 2009-08-07 | |
US61/232,132 | 2009-08-07 | ||
PCT/US2010/044703 WO2011017611A1 (en) | 2009-08-07 | 2010-08-06 | Lipidated oxoadenine derivatives |
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JP2013501730A true JP2013501730A (ja) | 2013-01-17 |
JP5759992B2 JP5759992B2 (ja) | 2015-08-05 |
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US (1) | US9044481B2 (ja) |
EP (2) | EP2461690A4 (ja) |
JP (1) | JP5759992B2 (ja) |
KR (1) | KR20120055623A (ja) |
CN (1) | CN102469790B (ja) |
AU (1) | AU2010279299B2 (ja) |
BR (1) | BR112012002349A2 (ja) |
CA (1) | CA2768195A1 (ja) |
EA (1) | EA023536B1 (ja) |
ES (1) | ES2732999T3 (ja) |
MX (1) | MX2012001524A (ja) |
SG (1) | SG178237A1 (ja) |
TR (1) | TR201909600T4 (ja) |
WO (1) | WO2011017611A1 (ja) |
ZA (1) | ZA201200646B (ja) |
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JP2016500068A (ja) * | 2012-11-20 | 2016-01-07 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーGlaxoSmithKline LLC | 新規化合物 |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04103597A (ja) * | 1990-08-20 | 1992-04-06 | Miyoshi Oil & Fat Co Ltd | 8―ヒドロキシアデノシン―5′―リン酸を含むアデノシンモノホスフェート系三量体、その製造方法及びその化合物からなる蛋白質合成阻害剤 |
JPH093091A (ja) * | 1995-06-21 | 1997-01-07 | Rikagaku Kenkyusho | ヌクレオシド誘導体物質、その製造法及び抗腫瘍剤 |
WO2007034881A1 (ja) * | 2005-09-22 | 2007-03-29 | Dainippon Sumitomo Pharma Co., Ltd. | 新規アデニン化合物 |
WO2008005555A1 (en) * | 2006-07-07 | 2008-01-10 | Gilead Sciences, Inc. | Modulators of toll-like receptor 7 |
WO2008114008A1 (en) * | 2007-03-19 | 2008-09-25 | Astrazeneca Ab | 9-substituted-8-oxo-adenine compounds as toll-like receptor (tlr7 ) modulators |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW552261B (en) * | 1996-07-03 | 2003-09-11 | Japan Energy Corp | Novel purine derivative |
WO2003066649A1 (en) * | 2002-02-04 | 2003-08-14 | Biomira Inc. | Immunostimulatory, covalently lipidated oligonucleotides |
WO2010018131A1 (en) * | 2008-08-11 | 2010-02-18 | Smithkline Beecham Corporation | Purine derivatives for use in the treatment of allergic, inflammatory and infectious diseases |
JP5519670B2 (ja) * | 2008-08-11 | 2014-06-11 | グラクソスミスクライン エルエルシー | アレルギー性、炎症性及び感染性疾患治療用のプリン誘導体 |
-
2010
- 2010-08-06 MX MX2012001524A patent/MX2012001524A/es active IP Right Grant
- 2010-08-06 BR BR112012002349A patent/BR112012002349A2/pt not_active Application Discontinuation
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- 2010-08-06 CA CA2768195A patent/CA2768195A1/en not_active Abandoned
- 2010-08-06 SG SG2012007522A patent/SG178237A1/en unknown
- 2010-08-06 KR KR1020127005993A patent/KR20120055623A/ko not_active Application Discontinuation
- 2010-08-06 EA EA201290036A patent/EA023536B1/ru not_active IP Right Cessation
- 2010-08-06 ES ES16190246T patent/ES2732999T3/es active Active
- 2010-08-06 TR TR2019/09600T patent/TR201909600T4/tr unknown
-
2012
- 2012-01-25 ZA ZA2012/00646A patent/ZA201200646B/en unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04103597A (ja) * | 1990-08-20 | 1992-04-06 | Miyoshi Oil & Fat Co Ltd | 8―ヒドロキシアデノシン―5′―リン酸を含むアデノシンモノホスフェート系三量体、その製造方法及びその化合物からなる蛋白質合成阻害剤 |
JPH093091A (ja) * | 1995-06-21 | 1997-01-07 | Rikagaku Kenkyusho | ヌクレオシド誘導体物質、その製造法及び抗腫瘍剤 |
WO2007034881A1 (ja) * | 2005-09-22 | 2007-03-29 | Dainippon Sumitomo Pharma Co., Ltd. | 新規アデニン化合物 |
WO2008005555A1 (en) * | 2006-07-07 | 2008-01-10 | Gilead Sciences, Inc. | Modulators of toll-like receptor 7 |
WO2008114008A1 (en) * | 2007-03-19 | 2008-09-25 | Astrazeneca Ab | 9-substituted-8-oxo-adenine compounds as toll-like receptor (tlr7 ) modulators |
Non-Patent Citations (1)
Title |
---|
JPN6014041879; CHAN,M. et al.: 'Synthesis and Immunological Characterization of Toll-Like Receptor 7 Agonistic Conjugates' Bioconjugate Chemistry Vol.20, 2009, p.1194-1200 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016500068A (ja) * | 2012-11-20 | 2016-01-07 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーGlaxoSmithKline LLC | 新規化合物 |
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BR112012002349A2 (pt) | 2015-10-13 |
WO2011017611A1 (en) | 2011-02-10 |
ES2732999T3 (es) | 2019-11-27 |
JP5759992B2 (ja) | 2015-08-05 |
KR20120055623A (ko) | 2012-05-31 |
AU2010279299A1 (en) | 2012-03-29 |
CN102469790B (zh) | 2014-12-03 |
EA023536B1 (ru) | 2016-06-30 |
EP3199159B1 (en) | 2019-04-10 |
EP2461690A4 (en) | 2013-03-27 |
ZA201200646B (en) | 2013-06-26 |
AU2010279299B2 (en) | 2015-10-01 |
EA201290036A1 (ru) | 2012-12-28 |
TR201909600T4 (tr) | 2019-07-22 |
US9044481B2 (en) | 2015-06-02 |
CA2768195A1 (en) | 2011-02-10 |
EP3199159A1 (en) | 2017-08-02 |
US20120135963A1 (en) | 2012-05-31 |
CN102469790A (zh) | 2012-05-23 |
SG178237A1 (en) | 2012-03-29 |
MX2012001524A (es) | 2012-02-29 |
EP2461690A1 (en) | 2012-06-13 |
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