JP2021523226A - Rip1阻害剤化合物並びにそれを製造及び使用するための方法 - Google Patents
Rip1阻害剤化合物並びにそれを製造及び使用するための方法 Download PDFInfo
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- JP2021523226A JP2021523226A JP2021510284A JP2021510284A JP2021523226A JP 2021523226 A JP2021523226 A JP 2021523226A JP 2021510284 A JP2021510284 A JP 2021510284A JP 2021510284 A JP2021510284 A JP 2021510284A JP 2021523226 A JP2021523226 A JP 2021523226A
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- oxo
- oxobenzoxazapine
- methyl
- triazole
- oxazepine
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D267/02—Seven-membered rings
- C07D267/08—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D267/12—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D267/14—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
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- A61P37/00—Drugs for immunological or allergic disorders
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Abstract
【解決手段】本明細書では、受容体相互作用タンパク質−1(RIP1)キナーゼ阻害剤化合物などのキナーゼ阻害剤化合物並びにそのような阻害剤化合物を含む医薬組成物及び組合せが開示される。開示される化合物、医薬組成物及び/又は組合せは、キナーゼ関連疾患又は状態、特にRIP1関連疾患又は状態を治療又は予防するために使用され得る。
【選択図】なし
Description
本出願は、2018年5月3日に出願された先願である米国仮特許出願第62/666,462号の出願日の利益を主張するものであり、その全体が参照により本明細書に援用される。
本開示は、受容体相互作用タンパク質キナーゼ−1(「RIP1」)の阻害並びにRIP1が関連する疾患及び/又は状態の治療等のための化合物並びにその化合物を製造及び使用する方法に関する。
受容体相互作用タンパク質キナーゼ−1(本明細書では「RIP1」と称する)は、チロシンキナーゼ様ファミリーに属する、自然免疫シグナル伝達に関与するセリン/スレオニンプロテインキナーゼである。RIP1は、細胞シグナル伝達の調節において中心的な役割を果たし、そのプログラム細胞死における役割は、炎症性腸疾患、乾癬、他の疾患等の様々な炎症性疾患、及び/又は炎症、及び/又はネクロプトーシス細胞死が関与する状態と関連付けられている。
本明細書では、式I
を満たす構造を有することができる。特定の環Bの実施形態は、ジアゾール、トリアゾール、オキサジアゾール、オキサゾール又はピリジニルである。好適なトリアゾールの例としては、次に示すもののいずれかが挙げられる。
Xは、ハロゲン又はトリフラートであり;
PGは、アミン保護基であり;及び
環B、L、R1、R2、R4、R5、m、n及びpのそれぞれは、上述の化合物実施形態の任意の1つ又は複数に記載された通りである。
I.用語の概説
以下に示す用語及び方法の説明は、本開示をより詳細に説明するため及び本開示の実施において当業者を指導するために提供するものである。単数形「1つの(a)」、「1つの(an)」及び「その」)は、文脈がそうでないことを明確に指示していない限り、1つ又は2つ以上を意味する。「又は」という語は、文脈がそうでないことを明確に指示していない限り、提示された代替的な構成要素の単一の構成要素又は2つ以上の構成要素の組合せを指す。本明細書において用いられる「含む」は、「包含する」を意味する。したがって、「A又はBを含む」は、「A、B又はA及びBを包含する」を意味し、追加の構成要素を排除しない。本明細書に引用する特許及び特許出願を含む全ての参考文献は、参照により本明細書に援用される。
(i)患者若しくは対象における疾患若しくは状態の発生を予防すること、特にこの種の患者若しくは対象がその状態の素因を有しているが、依然としてそれを有すると診断されていない場合に予防すること;
(ii)疾患若しくは状態を阻害すること、例えばその進行を停止若しくは緩徐化させること;
(iii)疾患又は状態を緩和すること、例えば症状を縮小させるか、又は疾患、若しくは状態、若しくはその症状を退行させること;又は
(iv)疾患若しくは状態を安定化させること
が挙げられる。
A.化合物
本明細書では、RIP1を阻害するため、及び/又はRIP1が関連する疾患及び/又は状態を治療するために有用な化合物並びにそのような化合物を含む医薬組成物を開示する。一部の実施形態において、化合物は、選択的キナーゼ阻害剤である。例えば、例示的な化合物は、RIP1を、RIP2、RIP3又はRIP2及びRIP3の両方に対して選択的に阻害する能力を有する。一部の実施形態において、本開示化合物は、式I
環Bは、5員環又は6員環のヘテロアリールであり;
Lは、ヘテロ原子又はRaであり、但し、Raは、H又はDではなく;
Zは、C1〜10脂肪族(例えば、C1〜10アルキル、C2〜10アルケニル、C2〜10アルキニル又はC3〜6シクロアルキルである);又は
R1は、ハロゲン、−C≡CH又は−リンカー−R6基であり、リンカーは、Raであり、但し、Raは、H又はDではなく、及びR6は、Rb、−C(Rf)3又は−C(Rf)=C(Rf)2であり;
R2及びR3は、独立に、Raであり;
R4及びR5は、独立に、Reであり;
Raは、それぞれの場合に独立に、H又はD(LがRaである実施形態を除く)、C1〜10脂肪族(例えば、C1〜10アルキル、C2〜10アルケニル、C2〜10アルキニル又はC3〜6シクロアルキル)、C1〜10ハロ脂肪族、C5〜10芳香族又はC3〜6複素環であり;
Rbは、それぞれの場合に独立に、−OH、−SH、−ORc、−SRc、−NRdRd、−Si(Ra)3、−C(O)OH、−C(O)ORc又は−C(O)NRdRdであり;
Rcは、それぞれの場合に独立に、C1〜10アルキル(これは、1、2又は3個のReで置換され得る)、C2〜10アルケニル(これは、1、2又は3個のReで置換され得る)、C2〜10アルキニル(これは、1、2又は3個のReで置換され得る)、C3〜6シクロアルキル(これは、1、2又は3個のReで置換され得る)又はC5〜10芳香族(これは、1、2又は3個のReで置換され得る)であり;
Rdは、それぞれの場合に独立に、H;C1〜6アルキル(これは、1、2又は3個のReで置換され得る);C3〜6シクロアルキル(これは、1、2又は3個のReで置換され得る);C3〜6複素環(これは、1、2又は3個のReで置換され得る);C5〜10アリール(これは、1、2又は3個のRbで置換され得る);C5〜10ヘテロアリール(これは、1、2又は3個のReで置換され得る)であるか;又は2個のRd基は、それらが結合されている窒素と一緒になって、C3〜9複素環(これは、1個又は複数のReで置換され得る)若しくはC5〜10ヘテロアリール(これは、1個又は複数のReで置換され得る)を提供し;
Reは、それぞれの場合に独立に、ハロゲン、C1〜6アルキル、C2〜10アルケニル、C2〜10アルキニル、C1〜6ハロアルキル、C3〜6シクロアルキル、C5〜10ヘテロアリール又は−ORaであり;
Rfは、それぞれの場合に独立に、Ra、Rb若しくはReであるか、又は2個のRf基は、それらが結合されている炭素原子と一緒になって、C3〜6シクロアルキル基(これは、1個又は複数のReで置換され得る)若しくはC3〜10複素環(これは、1個又は複数のReで置換され得る)を提供し;
mは、1〜4、例えば1、2、3又は4、であり、特定の実施形態では1又は2であり;
nは、0、1又は2であり;及び
pは、0、1、2、3、4又は5である。
環Bは、5員環又は6員環のヘテロアリールであり;
Lは、ヘテロ原子又はRaであり、但し、Raは、H又はDではなく;
R1は、ハロゲン、−C≡CH又は−リンカー−R6基であり、リンカーは、Raであり、但し、Raは、H又はDではなく、及びR6は、Rb、−C(Rf)3又は−C(Rf)=C(Rf)2であり;
R2及びR3は、独立に、Raであり;
R4及びR5は、独立に、Reであり;
Raは、それぞれの場合に独立に、H又はD(LがRaである実施形態を除く)、C1〜10脂肪族(例えば、C1〜10アルキル、C2〜10アルケニル、C2〜10アルキニル又はC3〜6シクロアルキル)、C1〜10ハロ脂肪族、C5〜10芳香族又はC3〜6複素環であり;
Rbは、それぞれの場合に独立に、−OH、−SH、−ORc、−SRc、−NRdRd、−Si(Ra)3、−C(O)OH、−C(O)ORc又は−C(O)NRdRdであり;
Rcは、それぞれの場合に独立に、C1〜10アルキル(これは、1、2又は3個のReで置換され得る)、C2〜10アルケニル(これは、1、2又は3個のReで置換され得る)、C2〜10アルキニル(これは、1、2又は3個のReで置換され得る)、C3〜6シクロアルキル(これは、1、2又は3個のReで置換され得る)又はC5〜10芳香族(これは、1、2又は3個のReで置換され得る)であり;
Rdは、それぞれの場合に独立に、H;C1〜6アルキル(これは、1、2又は3個のReで置換され得る);C3〜6シクロアルキル(これは、1、2又は3個のReで置換され得る);C3〜6複素環(これは、1、2又は3個のReで置換され得る);C5〜10アリール(これは、1、2又は3個のRbで置換され得る);C5〜10ヘテロアリール(これは、1、2又は3個のReで置換され得る)であるか;又は2個のRd基は、それらが結合されている窒素と一緒になって、C3〜9複素環(これは、1個又は複数のReで置換され得る)若しくはC5〜10ヘテロアリール(これは、1個又は複数のReで置換され得る)を提供し;
Reは、それぞれの場合に独立に、ハロゲン、C1〜6アルキル、C2〜10アルケニル、C2〜10アルキニル、C1〜6ハロアルキル、C3〜6シクロアルキル、C5〜10ヘテロアリール又は−ORaであり;
Rfは、それぞれの場合に独立に、Ra、Rb若しくはReであるか、又は2個のRf基は、それらが結合されている炭素原子と一緒になって、C3〜6シクロアルキル基(一部の実施形態では、C3〜6シクロアルキル基は、1個又は複数のReで置換されている)若しくはC3〜10複素環(一部の実施形態では、C3〜10複素環式基は、1個又は複数のReで置換されている)を提供し;
mは、1〜4、例えば1、2、3又は4であり、特定の実施形態では1又は2であり;
nは、0、1又は2であり;及び
pは、0、1、2、3、4又は5である。
を満たす構造を有することができる。一部の実施形態において、5員環のヘテロアリール基は、ジアゾール、トリアゾール、オキサジアゾール又はオキサゾールである。例示的なトリアゾールとしては、次に示すもののいずれかが挙げられる。
I−1:エチル(S)−3−(3−(5−ベンジル−1H−1,2,4−トリアゾール−3−カルボキサミド)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−7−イル)プロパノエート;
I−2:(S)−N−(7−(3−((1H−インダゾール−5−イル)アミノ)−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−5−ベンジル−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−3:(S)−N−(7−(3−((1H−インダゾール−6−イル)アミノ)−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−5−ベンジル−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−4:(S)−5−ベンジル−N−(7−(3−((6,7−ジメトキシキナゾリン−4−イル)アミノ)−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−5:エチル(S)−3−(3−(1−(2−フルオロベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−7−イル)プロパノエート;
I−6:(S)−3−(3−(1−(2−フルオロベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−7−イル)プロパン酸;
I−7:(S)−N−(7−(3−((1H−インダゾール−6−イル)アミノ)−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1−(2−フルオロベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−8:エチル(S)−3−(3−(1−(2,6−ジクロロベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−7−イル)プロパノエート;
I−9:(S)−3−(3−(5−ベンジル−1H−1,2,4−トリアゾール−3−カルボキサミド)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−7−イル)プロパン酸;
I−10:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−(3−オキソ−3−(ピロリジン−1−イル)プロピル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−11:(S)−5−ベンジル−N−(5−メチル−7−(3−モルホリノ−3−オキソプロピル)−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−12:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−(3−オキソ−3−(キノリン−7−イルアミノ)プロピル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−13:(S)−5−ベンジル−N−(7−(3−(シクロプロピルアミノ)−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−14:(S)−5−ベンジル−N−(7−(3−ヒドロキシプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−15:(S)−5−ベンジル−N−(7−(4−ヒドロキシブチル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−16:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−(4−(ピリジン−2−イルメトキシ)ブチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−17:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−(4−(ピリジン−2−イルアミノ)ブチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−18:(S)−1−(2,6−ジクロロベンジル)−N−(5−メチル−4−オキソ−7−(3−オキソ−3−(ピロリジン−1−イル)プロピル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−19:(S)−N−(7−(3−(シクロプロピルアミノ)−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1−(2,6−ジクロロベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−20:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−((4−(ピリジン−4−イル)ピペラジン−1−イル)メチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−21:(S)−1−(2,6−ジクロロベンジル)−N−(5−メチル−4−オキソ−7−((4−(ピリジン−4−イル)ピペラジン−1−イル)メチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−22:(S,E)−5−ベンジル−N−(5−メチル−4−オキソ−7−(3−オキソ−3−(ピロリジン−1−イル)プロプ−1−エン−1−イル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−23:(S,E)−5−ベンジル−N−(7−(3−(シクロプロピルアミノ)−3−オキソプロプ−1−エン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−24:(S)−5−ベンジル−N−(7−((5,6−ジヒドロ−[1,2,4]トリアゾロ[1,5−a]ピラジン−7(8H)−イル)メチル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−25:(S)−1−ベンジル−N−(7−((5,6−ジヒドロ−[1,2,4]トリアゾロ[1,5−a]ピラジン−7(8H)−イル)メチル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−26:(S)−1−ベンジル−N−(7−(3−(シクロプロピルアミノ)−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−27:(S)−N−(7−(3−(シクロプロピルアミノ)−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−5−(2,4−ジフルオロベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−28:(S)−5−ベンジル−N−(7−(3−ヒドロキシ−3−メチルブチル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−29:(S)−1−ベンジル−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−30:(S)−5−ベンジル−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−31:(S)−N−(7−(3−アミノ−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−5−ベンジル−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−32:(S)−N−(7−(3−アミノ−3−オキソプロピル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1−ベンジル−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−33:(S)−1−ベンジル−N−(5−メチル−4−オキソ−7−(3−オキソ−3−(ピロリジン−1−イル)プロピル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−34:(S)−5−(2,4−ジフルオロベンジル)−N−(5−メチル−4−オキソ−7−(3−オキソ−3−(ピロリジン−1−イル)プロピル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−35:(S)−5−ベンジル−N−(7−(5−ヒドロキシペント−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−36:(S)−5−ベンジル−3−((7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)カルバモイル)−1,2,4−トリアゾール−1−イド;
I−37:(S)−1−ベンジル−N−(5−メチル−4−オキソ−7−(4−(キノリン−6−イルオキシ)ブト−1−イン−1−イル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−38:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−(4−(キノリン−6−イルオキシ)ブト−1−イン−1−イル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−39:(S)−1−ベンジル−N−(5−メチル−4−オキソ−7−((2−(トリフルオロメチル)−5,6−ジヒドロ−[1,2,4]トリアゾロ[1,5−a]ピラジン−7(8H)−イル)メチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−40:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−((2−(トリフルオロメチル)−5,6−ジヒドロ−[1,2,4]トリアゾロ[1,5−a]ピラジン−7(8H)−イル)メチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−41:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−(4−(キノリン−7−イルオキシ)ブト−1−イン−1−イル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−42:(S)−1−ベンジル−N−(5−メチル−4−オキソ−7−(4−(キノリン−7−イルオキシ)ブト−1−イン−1−イル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−43:(S)−5−(2,4−ジフルオロベンジル)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−44:(S)−1−ベンジル−N−(5−メチル−4−オキソ−7−(4−(キノリン−5−イルオキシ)ブト−1−イン−1−イル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−45:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−(4−(キノリン−5−イルオキシ)ブト−1−イン−1−イル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−46:(S)−1−ベンジル−N−(5−メチル−4−オキソ−7−((3−(トリフルオロメチル)−5,6−ジヒドロ−[1,2,4]トリアゾロ[4,3−a]ピラジン−7(8H)−イル)メチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−47:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−((3−(トリフルオロメチル)−5,6−ジヒドロ−[1,2,4]トリアゾロ[4,3−a]ピラジン−7(8H)−イル)メチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−48:(S)−1−ベンジル−N−(7−(3,3−ジメチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−49:(S)−5−ベンジル−N−(7−(3,3−ジメチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−50:(S)−1−ベンジル−N−(7−((1−ヒドロキシシクロブチル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−51:(S)−5−ベンジル−N−(7−((1−ヒドロキシシクロブチル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−52:(S)−1−ベンジル−N−(7−((1−ヒドロキシシクロペンチル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−53:(S)−5−ベンジル−N−(7−((1−ヒドロキシシクロペンチル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−54:(S)−1−ベンジル−N−(7−((4−ヒドロキシテトラヒドロ−2H−ピラン−4−イル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−55:(S)−5−ベンジル−N−(7−((4−ヒドロキシテトラヒドロ−2H−ピラン−4−イル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−56:(S)−i−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−4−フェノキシピコリンアミド;
I−57:(S)−5−ベンジル−N−(7−((3−ヒドロキシオキセタン−3−イル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−58:(S)−1−ベンジル−N−(7−((3−ヒドロキシオキセタン−3−イル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−59:(S)−5−ベンジル−N−(5−メチル−7−(3−メチルブト−3−エン−1−イン−1−イル)−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−60:(S)−5−ベンジル−N−(7−イソペンチル−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−61:(S)−5−ベンジル−N−(7−(3−メトキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−62:(S)−1−ベンジル−N−(8−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−63:(S)−5−ベンジル−N−(8−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−64:(S)−N−(8−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−4−フェノキシピコリンアミド;
I−65:(S)−5−(2,6−ジクロロベンジル)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−66:(S)−5−ベンジル−N−(5−メチル−4−オキソ−8−((2−(トリフルオロメチル)−5,6−ジヒドロ−[1,2,4]トリアゾロ[1,5−a]ピラジン−7(8H)−イル)メチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−67:(S)−1−ベンジル−N−(5−メチル−4−オキソ−8−((2−(トリフルオロメチル)−5,6−ジヒドロ−[1,2,4]トリアゾロ[1,5−a]ピラジン−7(8H)−イル)メチル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−68:(S)−N−(7−(3−ヒドロキシ−3−(メチル−d3)ブト−1−イン−1−イル−4,4,4−d3)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−4−フェノキシピコリンアミド;
I−69:(S)−5−ベンジル−N−(7−(3−ヒドロキシ−3−(メチル−d3)ブト−1−イン−1−イル−4,4,4−d3)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−70:(R)−5−ベンジル−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−71:(S)−5−ベンジル−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1,3,4−オキサジアゾール−2−カルボキサミド;
I−72:(S)−N−(8−((3−ヒドロキシオキセタン−3−イル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−4−フェノキシピコリンアミド;
I−73:(S)−5−ベンジル−N−(8−((3−ヒドロキシオキセタン−3−イル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−74:(3S,3aR,6R,6aS)−6−(((S)−3−(5−ベンジル−1H−1,2,4−トリアゾール−3−カルボキサミド)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−7−イル)エチニル)−6−ヒドロキシヘキサヒドロフロ[3,2−b]フラン−3−イルベンゾエート;
I−75:5−ベンジル−N−((S)−7−(((3R,3aS,6S,6aR)−3,6−ジヒドロキシヘキサヒドロフロ[3,2−b]フラン−3−イル)エチニル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−76:メチル(S)−4−(3−(5−ベンジル−1H−1,2,4−トリアゾール−3−カルボキサミド)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−7−イル)−2,2−ジメチルブト−3−イノエート;
I−77:(S)−1−ベンジル−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−ピラゾール−3−カルボキサミド;
I−78:(S)−5−(3−フルオロベンジル)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−79:(S)−5−(4−フルオロベンジル)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−80:(S)−5−(2−フルオロベンジル)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−81:(S)−5−ベンジル−N−(7−エチニル−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−82:(S)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1−(2−メチルベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−83:(S)−1−([1,1’−ビフェニル]−4−イルメチル)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−84:(S)−1−(2,6−ジメチルベンジル)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−85:(S)−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1−イソブチル−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−86:(S)−5−ベンジル−N−エチル−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−87:(S)−5−ベンジル−N−(7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)イソオキサゾール−3−カルボキサミド;
I−88:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−((1,2,3,4−テトラヒドロイソキノリン−7−イル)エチニル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−89:(S)−N−(7−(3,3−ジメチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−5−(2−フルオロベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−90:(S)−1−(2,6−ジメチルベンジル)−N−(7−(3,3−ジメチルブト−1−イン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−91:(S)−5−ベンジル−N−(5−エチル−7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−92:(S)−N−(5−エチル−7−(3−ヒドロキシ−3−メチルブト−1−イン−1−イル)−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−5−(3−フルオロベンジル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−93:(S)−5−ベンジル−N−(7−(3−メチルブト−3−エン−1−イン−1−イル)−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−94:(S,Z)−5−ベンジル−N−(7−(2−クロロ−3−ヒドロキシ−3−メチルブト−1−エン−1−イル)−5−メチル−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−95:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−(3−(ピロリジン−1−イル)プロプ−1−イン−1−イル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;
I−96:(S)−5−ベンジル−N−(5−メチル−7−(3−モルホリノプロプ−1−イン−1−イル)−4−オキソ−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド;又は
I−97:(S)−5−ベンジル−N−(5−メチル−4−オキソ−7−((トリメチルシリル)エチニル)−2,3,4,5−テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−1H−1,2,4−トリアゾール−3−カルボキサミド。
本明細書に記載する化合物は、単独で、互いに組み合わせて、別々の医薬組成物中で、単一の医薬組成物中で一緒に又は他の確立された療法と補助的に若しくは併用して使用することができる。1種若しくは複数の化合物又は1種の化合物(又は複数の化合物)を含む組成物は、1回又は複数回投与することができる。一部の実施形態において、本発明の化合物は、治療される障害又は状態に有用な他の治療薬と併用することができる。これらの他の治療薬は、本開示化合物と、同時に、任意の順序で連続的に同じ投与経路又は異なる投与経路で投与することができる。連続投与する場合、本化合物及び治療薬は、少なくとも1種の化合物及び治療薬の効果持続時間が少なくとも1種の他の化合物及び/又は治療薬の効果持続時間と重複するように投与され得る。4種の成分を含む組合せの例示的な実施形態において、最初に投与される成分の効果持続時間は、2番目、3番目及び4番目の成分の効果持続時間と重複し得るが、2番目、3番目及び4番目の成分の効果持続時間は、独立に、互いに重複してもしなくてもよい。4種の成分を含む組合せの他の例示的な実施形態において、最初に投与される成分の効果持続時間は、2番目の成分の効果持続時間と重複するが、3番目又は4番目とは重複せず;2番目の成分の効果持続時間は、最初及び3番目の成分の効果持続時間と重複し;4番目の成分の効果持続時間は、3番目の成分のものとのみ重複する。一部の実施形態において、全ての化合物及び/又は治療薬の効果持続時間は、互いに重複する。
鎮痛剤 − モルヒネ、フェンタニル、ヒドロモルフォン、オキシコドン、コデイン、アセトアミノフェン、ヒドロコドン、ブプレノルフィン、トラマドール、ベンラファキシン、フルピルチン、メペリジン、ペンタゾシン、デキストロモラミド、ジピパノン;
抗生物質 − アミノグリコシド(例えば、アミカシン、ゲンタマイシン、カナマイシン、ネオマイシン、ネチルマイシン、トブラマイシン及びパロマイシン)、カルバペネム(例えば、エルタペネム、ドリペネム、イミペネム、シラスタチン及びメロペネム)、セファロスポリン(例えば、セファドロキシル、セファゾリン、セファロチン、セファレキシン、セファクロル、セファマンドール、セフォキシチン、セフプロジル、セフロキシム、セフィキシム、セフジニル、セフジトレン、セフォペラゾン、セフォタキシム、セフポドキシム、セフタジジム、セフチブテン、セフチゾキシム、セフトリアキソン、セフェピム及びセフォビプロール、グリコペプチド(例えば、テイコプラニン、バンコマイシン及びテラバンシン)、リンコサミド(例えば、クリンダマイシン及びインコマイシン、リポペプチド(例えば、ダプトマイシン)、マクロライド(アジスロマイシン、クラリスロマイシン、ジリスロマイシン、エリスロマイシン、ロキシスロマイシン、トロレアンドマイシン、テリスロマイシン及びスペクチノマイシン)、モノバクタム(例えば、アズトレオナム)、ニトロフラン(例えば、フラゾリドン及びニトロフラントイン)、ペニシリン(例えば、アモキシシリン、アンピシリン、アズロシリン、カルベニシリン、クロキサシリン、ジクロキサシリン、フルクロキサシリン、メズロシリン、メチシリン、ナフシリン、オキサシリン、ペニシリンG、ペニシリンV、ピペラシリン、テモシリン及びチカルシリン)、複合ペニシリン製剤(例えば、アモキシシリン/クラブラン酸、アンピシリン/スルバクタム、ピペラシリン/タゾバクタム、チカルシリン/クラブラン酸)、ポリペプチド(例えば、バシトラシン、コリスチン及びポリミキシンB)、キノロン(例えば、シプロフロキサシン、エノキサシン、ガチフロキサシン、レボフロキサシン、ロメフロキサシン、モキシフロキサシン、ナリジクス酸、ノルフロキサシン、オフロキサシン、トロバフロキサシン、グレパフロキサシン、スパルフロキサシン及びテマフロキサシン)、スルホンアミド(例えば、マフェニド、スルホンアミドクリソイジン、スルファセタミド、スルファジアジン、スルファジアジン銀、スルファメチゾール、スルファメトキサゾール、スルファニルイミド、スルファサラジン、スルフィソキサゾール、トリメトプリム及びトリメトプリム−スルファメトキサゾール)、テトラサイクリン(例えば、デメクロサイクリン、ドキシサイクリン、ミノサイクリン、オキシテトラサイクリン及びテトラサイクリン)、抗酸菌化合物(例えば、クロファジミン、ダプソン、カプレオマイシン、サイクロセリン、エタンブトール、エチオナミド、イソニアジド、ピラジンアミド、リファンピシン(リファンピン)、リファブチン、リファペンチン及びストレプトマイシン)並びに他のもの、例えばアルスフェナミン、クロラムフェニコール、ホスホマイシン、フシジン酸、リネゾリド、メトロニダゾール、ムピロシン、プラテンシマイシン、キヌプリスチン/ダルホプリスチン、リファキシミン、チアムフェニコール、チゲサイクリン及びチミダゾール;
抗体 − 抗TNF−α抗体、例えばインフリキシマブ(Remicade(商標))、アダリムマブ、ゴリムマブ、セルトリズマブ;抗−B細胞抗体、例えばリツキシマブ;抗IL−6抗体、例えばトシリズマブ;抗IL−1抗体、例えばアナキンラ;抗PD−1及び/又は抗PD−L1抗体、例えばニボルマブ、ペンブロリズマブ、ピジリズマブ、BMS−936559、MPDL3280A、AMP−224、MEDI4736;イキセキズマブ、ブロダルマブ、オファツムマブ、シルクマブ、クレノリキシマブ、クラザキウマブ、フェザキヌマブ、フレチクマブ、マブリリムマブ、オクレリズマブ、サリルマブ、セクキヌマブ、トラリズマブ、ザノリムマブ;
抗凝血剤 − ワルファリン(Coumadin(商標))、アセノクマロール、フェンプロクモン、アトロメンチン、フェニンジオン、ヘパリン、フォンダパリヌクス、イドラパリヌクス、リバロキサバン、アピキサバン、ヒルジン、レピルジン、ビバリルジン、アルガトロバム、ダビガトラン、キシメラガトラン、バトロキソビン、ヘメンチン;
抗炎症剤 − ステロイド、例えばブデソニド、非ステロイド性抗炎症剤、例えばアミノサリチレート(例えば、スルファサラジン、メサラミン、オルサラジン及びバルサラジド)、シクロオキシゲナーゼ阻害剤(COX−2阻害剤、例えばロフェコキシブ、セレコキシブ)、ジクロフェナク、エトドラク、ファモチジン、フェノプロフェン、フルルビプロフェン、ケトプロフェン、ケトロラク、イブプロフェン、インドメタシン、メクロフェナメート、メフェナム酸、メロキシカム、ナンブメトン、ナプロキセン、オキサプロジン、ピロキシカム、サルサレート、スリンダク、トルメチン;
免疫抑制剤 − メルカプトプリン、コルチコステロイド、例えばデキサメタゾン、ヒドロコルチゾン、プレドニゾン、メチルプレドニゾロン及びプレドニゾロン、アルキル化剤、例えばシクロホスファミド、カルシニューリン阻害剤、例えばシクロスポリン、シロリムス及びタクロリムス、イノシン一リン酸脱水素酵素(IMPDH)阻害剤、例えばミコフェノレート、ミコフェノール酸モフェチル及びアザチオプリン並びに細胞性免疫を抑制しながらレシピエントの液性免疫応答を完全に保つように設計された剤(様々な抗体(例えば、抗リンパ球グロブリン(ALG)、抗胸腺細胞グロブリン(ATG)、モノクローナル抗T細胞抗体(OKT3))及び放射線照射を含む)。アザチオプリンは、現在、Salix Pharmaceuticals, Inc.から商品名Azasanで入手可能であり;メルカプトプリンは現在、Gate Pharmaceuticals, Inc.から商品名Purinetholで入手可能であり;プレドニゾン及びプレドニゾロンは、現在、Roxane Laboratories, Incから入手可能であり;メチルプレドニゾロンは、現在、Pfizerから入手可能であり;シロリムス(ラパマイシン)は、現在、Wyeth-Ayerstから商品名Rapamuneで入手可能であり;タクロリムスは、現在、Fujisawaから商品名Prografで入手可能であり;シクロスポリンは、現在、Novartisから商品名Sandimmuneで、且つAbbottから商品名Gengrafで入手可能であり;IMPDH阻害剤、例えばミコフェノール酸モフェチル及びミコフェノール酸は、現在、Rocheから商品名Cellceptで、且つNovartisから商品名Myforticで入手可能であり;アザチオプリンは、現在、Glaxo Smith Klineから商品名Imuranで入手可能であり;抗体は、現在、Ortho Biotechから商品名Orthocloneで、Novartisから商品名Simulect(バシリキシマブ)で、且つRocheから商品名Zenapax(ダクリズマブ)で入手可能である;及び
グアニル酸シクラーゼC受容体アゴニスト又は腸分泌促進物質、例えばLinzessの名称で販売されているリナクロチド。
本発明化合物は、当業者に理解されているように、任意の好適な方法により調製することができる。以下の実施例において例示的な好適な方法の1つを特定の化合物を参照しながら示す。これは、次に示すスキーム1に従う第1反応ステップを含むことができる。
A.疾患/障害
開示された化合物に加えてその組合せ及び/又は医薬組成物は、インビボ又はエクスビボのいずれかでキナーゼを、1種若しくは複数の本開示化合物又は1種若しくは複数の本開示化合物を含む組成物と接触させることにより、RIP1キナーゼを阻害するために使用することができる。1種若しくは複数の開示化合物又は1種若しくは複数の開示化合物を含む組成物は、様々な疾患及び/又は障害の軽減、治療又は予防に使用することもできる。特定の実施形態において、開示化合物、開示化合物の組合せ又はその医薬組成物は、RIP1の阻害又はRIP1が関与する経路の阻害が治療的に有用である状態の治療に有用となり得る。一部の実施形態において、化合物は、RIP1キナーゼ活性を直接阻害する。特定の実施形態において、開示された化合物は、自己免疫性疾患、炎症性疾患、心血管疾患、神経障害、神経変性疾患、アレルギー性疾患、呼吸器疾患、腎臓疾患、癌、虚血状態、赤血球欠乏、肺及び脳損傷(例えば、虚血再灌流又はシスプラチン及び/又は脳血管障害により引き起こされるもの)並びに細菌及びウイルス感染の治療に有用である。
1種又は複数の本発明の活性化合物を含む医薬組成物は、任意の好適な方法、例えば混合、溶解、造粒、糖衣、磨り潰し、乳化、カプセル化、内包又は凍結乾燥プロセスにより製造することができる。医薬組成物は、1種又は複数の生理学的に許容される添加剤(例えば、希釈剤、担体又は補助剤)、1種又は複数のアジュバント又はこれらの組合せを用いて製剤化することにより、医薬的に使用することができる製剤を得ることができる。
本開示化合物、医薬組成物又は開示化合物の組合せは、一般に、意図された結果を達成するのに有効な量、例えばRIP1キナーゼを阻害するため及び/又は具体的な状態を治療、予防又は軽減するために有効な量で使用されることになる。開示化合物又はその医薬組成物は、治療効果を達成する目的で治療的に又は予防効果を達成する目的で予防的に投与することができる。治療効果とは、患者がその基礎にある障害に依然として悩まされている可能性の有無とは無関係に、感覚又は状態が改善されたと患者が報告するように、基礎にある治療される障害が根絶若しくは軽減されること及び/又は基礎にある障害に伴う1つ若しくは複数の症状が根絶若しくは軽減されることを意味する。例えば、アレルギーを患っている患者に化合物を投与することにより、基礎にあるアレルギー反応が根絶又は軽減された場合のみならず、患者がアレルゲンに曝露された後のアレルギーに付随する症状の重症度が低下するか又は期間が短縮されたと報告した場合も治療効果が得られている。他の例として、喘息に関連する治療効果としては、喘息発作が発症した後の呼吸の改善又は喘息が発症する頻度若しくは重症度の低下が挙げられる。治療効果としては、改善を実感するか否かに関わらず、疾患の進行が停止又は緩徐化することも挙げられる。
実施例1
本開示化合物は、上のスキームに例示したように、化合物200又は化合物206等の好適な出発化合物を用いて製造することができる。化合物200を生成するための代表的な方法をスキーム7Aに例示し、化合物206を生成するための代表的な方法をスキーム7Bに例示する。
1H nmr(400MHz,D6DMSO)δ 7.83(1H,d,J 8.0Hz,NH),7.45(1H,d,J 2.0Hz,オキソベンゾオキサザピンH−6),7.25(1H,dd,J 8.0,2.0Hz,オキソベンゾオキサザピンH−8),7.20−7.15(5H,m,オキソベンゾオキサザピンH−9,C6H5の4H),7.09−7.04(1H,m,C6H5の1H),5.47(1H,br s,OH),4.81−4.74(1H,m,オキソベンゾオキサザピンH−3),4.39−4.36(2H,m,オキソベンゾオキサザピンH−2の2H),3.84(2H,s,CH 2C6H5),3.28(3H,s,NCH3),1.44(6H,s,C(CH 3)2OH);m/z:442[M+H]+.
1H nmr(400MHz,CDCl3)δ 8.76(1H,dd,J 4.0,1.5Hz,キノリンH−2),8.03(2H,m,NH,キノリンH−4),8.01(1H,d,J 9.5Hz,キノリンH−8),7.99(1H,s,トリアゾールH−5),7.40(1H,dd,J 9.0,3.0Hz,キノリンH−7),7.37−7.7.33(4H,m,C6H5の4H,オキソベンゾオキサザピンH−6,H−8),7.28−7.24(3H,m,C6H5の3H,オキソベンゾオキサザピンH−6,H−8),7.12(1H,d,J 2.5Hz,キノリンH−5),7.10(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.36(2H,s,NCH 2C6H5),5.06(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.75(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.30(2H,t,J 7.0Hz,CCH2CH 2O),4.24(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.39(3H,s,NCH3),2.98(2H,t,J 7.0Hz,CCH 2CH2O);m/z:573[M+H]+(実測値[M+H]+,573.2244,C33H28N6O4 理論値[M+H]+ 573.2245).
1H nmr(400MHz,CDCl3)δ 8.73(1H,dd,J 4.0,1.5Hz,キノリンH−2),8.05(2H,m,NH,キノリンH−4),8.00(1H,d,J 9.5Hz,キノリンH−8),7.40(1H,dd,J 9.5,3.0Hz,キノリンH−7),7.34(1H,m,キノリンH−3),7.25(1H,dd,J 8.0,2.0Hz,オキソベンゾオキサザピンH−8),7.25−7.20(6H,m,C6H5,オキソベンゾオキサザピンH−7),7.11(1H,d,J 3.0Hz,キノリンH−5),7.09(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.02(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.67(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.29(2H,t,J 7.0Hz,CCH2CH 2O),4.26(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.14(2H,s,CH 2C6H5),3.37(3H,s,NCH3),2.98(2H,t,J 7.0Hz,CCH 2CH2O);13C nmr(100MHz,CDCl3)δ 168.7,156.6,149.7,148.0,144.3,136.0,134.9,131.0,130.8,129.2,128.8(2C),128.6,127.1,126.5,123.1,122.4,121.4,121.0,106.3,86.6,80.7,77.2,66.2,49.1,35.4,33.4,20.4,;m/z:573[M+H]+(実測値[M+H]+,573.2262,C33H28N6O4 理論値[M+H]+ 573.2245).
1H nmr(400MHz,CDCl3)δ 8.04(1H,d,J 7.5Hz,NH),8.00(1H,s,トリアゾールH−5),7.38−7.33(3H,m,C6H5の3H),7.27−7.24(2H,m,C6H5の2H),7.19(2H,m,オキソベンゾオキサザピンH−6,H−8),7.15(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.35(2H,s,NCH 2C6H5),5.09(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.73(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26−4.21(3H,m,オキソベンゾオキサザピンH−2の1H,NCH2CH2Nの2H),3.87(2H,s,ArCH2NCH2Cの2H),3.75(2H,s,ArCH2NCH2Cの2H),3.40(3H,s,NCH3),3.01(2H,td,J 5.0,1.5Hz,NCH2CH2Nの2H);13C nmr(100MHz,CDCl3)δ 168.8,158.4,156.6,153.5(q,J 39.5Hz),152.2,149.6,143.9,136.4,134.5,133.7,129.2,129.0,128.2,127.8,123.4,123.3,119.2(q,J 270.5Hz),77.2,60.6,54.3,50.7,49.2,48.4,47.1,35.6;19F nmr(380MHz,CDCl3)δ −65.4 m/z:582[M+H]+(実測値[M+H]+,582.2188,C27H26F3N9O3 理論値[M+H]+ 582.2183).
1H nmr(400MHz,CDCl3)δ 8.02(1H,d,J 7.5Hz,NH),7.27−7.21(6H,m,C6H5,オキソベンゾオキサザピンH−8),7.21(1H,dd,J 7.5,2.0Hz,オキソベンゾオキサザピンH−8),7.15(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.07(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.69(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.29−4.23(3H,m,オキソベンゾオキサザピンH−2の1H,NCH2CH2Nの2H),4.12(2H,s,CH 2C6H5),3.86(2H,s,ArCH2NCH2Cの2H),3.76(2H,s,ArCH2NCH2Cの2H),3.39(3H,s,NCH3),3.03(2H,t,J 5.5Hz,NCH2CH2Nの2H);13C nmr(100MHz,CDCl3)δ 168.8,158.7,153.4(q,J 39.5Hz),152.2,149.6,136.3,135.7,134.6,128.8,128.7,127.9,127.1,123.4,123.2,123.1,119.2(q,J 269.5Hz),77.1,60.7,50.4,49.4,48.6,47.1,35.6,33.0;19F nmr(380MHz,CDCl3)δ −65.3 m/z:582[M+H]+(実測値[M+H]+,582.2167,C27H26F3N9O3 理論値[M+H]+ 582.2183).
1H nmr(400MHz,CDCl3)δ 8.75(1H,dd,J 4.5,2.0Hz,キノリンH−2),8.09−8.06(2H,m,NH,キノリンH−4),7.70(1H,d,J 9.0Hz,キノリンH−5),7.50(1H,d,J 2.5Hz,キノリンH−8),7.27−7.17(9H,m,キノリンH−3,H−6,オキソベンゾオキサザピンH−6,H−8,C6H5),7.07(1H,d,J 8.5Hz,オキソベンゾオキサザピンH−9),5.00(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.31(2H,td,J 7.0,2.5Hz,OCH 2CH2C),4.24(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.13(2H,s,CH 2C6H5),3.36(3H,s,NCH3),2.97(2H,t,J 7.0Hz,OCH2CH 2C);13C nmr(100MHz,CDCl3)δ 168.7,159.6,158.6,150.3,149.6,149.5,136.0(2C),135.9,131.0,128.9,128.8,128.7,127.0,126.5,123.7,123.0,121.0,120.1,119.1,107.9,86.8,80.6,77.2,66.1,49.2,35.5,33.2,20.3;m/z:573[M+H]+(実測値[M+H]+,573.2269,C33H28N6O4 理論値[M+H]+ 573.2245).
1H nmr(400MHz,CDCl3)δ 8.20(1H,dd,J 4.5,2.0Hz,キノリンH−2),8.06(1H,dd,J 8.0,1.5Hz,キノリンH−4),8.03(1H,d,J 7.0Hz,NH),7.99(1H,s,トリアゾールH−5),7.70(1H,d,J 9.0Hz,キノリンH−5),7.45(1H,d,J 2.5Hz,キノリンH−8),7.37−7.33(3H,m,C6H5の3H,オキソベンゾオキサザピンH−6),7.27−7.22(6H,m,キノリンH−6,H−3,オキソベンゾオキサザピンH−8,C6H5の3H,オキソベンゾオキサザピンH−6),7.09(1H,dd,J 8.0,0.5Hz,オキソベンゾオキサザピンH−9),5.35(2H,s,NCH 2C6H5),5.06(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.75(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.33(2H,t,J 7.0Hz,OCH 2CH2C),4.23(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),3.39(3H,s,NCH3),2.98(2H,t,J 7.0Hz,OCH2CH 2C);13C nmr(100MHz,CDCl3)δ 168.8,159.4,158.4,156.6,150.6,149.8,149.7,143.9,135.9,135.7,133.7,130.9,129.2,128.9,128.2,126.5,123.7,123.1,121.0,119.9,119.1,108.2,86.6,80.7,77.1,66.1,54.3,49.1,38.6,35.5,20.3;m/z:573[M+H]+(実測値[M+H]+,573.2249,C33H28N6O4 理論値[M+H]+ 573.2245).
1H nmr(400MHz,CDCl3)δ 8.05(1H,d,J 7.5Hz,NH),7.27−7.20(3H,m,オキソベンゾオキサザピンH−6,H−8,C6H3F2の1H),7.10(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),6.82−6.74(2H,m,C6H3F2の2H),4.99(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.12(2H,s,CH 2C6H3F2),3.39(3H,s,NCH3),1.61(6H,s,C(CH 3)2OH);19F nmr(380MHz,CDCl3)δ −111.2;−113.2;m/z:478[M+H−H2O]+(実測値[M+H]+,496.1795,C25H23F2N5O4 理論値[M+H]+ 496.1791).
1H nmr(400MHz,CDCl3)δ 8.89(1H,dd,J 4.0,2.0Hz,キノリンH−2),8.63(1H,ddd,J 8.5,2.0,1.0Hz,キノリンH−4),8.02(1H,d,J 7.5Hz,NH),7.99(1H,s,トリアゾールH−5),7.70(1H,d,J 8.5Hz,キノリンH−8),7.59(1H,dd,J 8.5,7.5Hz,キノリンH−7),7.38−7.33(4H,m,キノリンH−3,C6H5の3H,オキソベンゾオキサザピンH−6),7.26−7.22(4H,m,オキソベンゾオキサザピンH−8,C6H5の3H,オキソベンゾオキサザピンH−6),7.09(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),6.89(1H,dd,J 7.5,0.5Hz,キノリンH−6),5.35(2H,s,NCH 2C6H5),5.06(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.73(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.35(2H,t,J 7.0Hz,OCH 2CH2C),4.24(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.37(3H,s,NCH3),3.03(2H,t,J 7.0Hz,OCH2CH 2C);m/z:573[M+H]+(実測値[M+H]+,573.2251,C33H28N6O4 理論値[M+H]+ 573.2245).
1H nmr(400MHz,CDCl3)δ 8.85(1H,dd,J 4.0,2.0Hz,キノリンH−2),8.64(1H,ddd,J 8.5,2.0,1.0Hz,キノリンH−4),8.07(1H,d,J 7.5Hz,NH),7.69(1H,d,J 8.5Hz,キノリンH−8),7.59(1H,dd,J 8.5,7.5Hz,キノリンH−3),7.26−7.17(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.08(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),6.90(1H,dd,J 8.0,0.5Hz,キノリンH−6),5.02(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.36(2H,t,J 7.0Hz,OCH 2CH2C),4.25(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.13(2H,s,CH 2C6H5),3.36(3H,s,NCH3),3.04(2H,t,J 7.0Hz,OCH2CH 2C);13C nmr(100MHz,CDCl3)δ 168.7,158.5,153.9,150.6,149.7,148.9,136.0,131.0,130.9,129.4,128.8,128.7,127.0,126.5,123.1,121.8,121.0,120.9,120.3,105.4,86.7,80.7,77.2,49.1,35.5,33.2,20.5;m/z:573[M+H]+(実測値[M+H]+,573.2266,C33H28N6O4 理論値[M+H]+ 573.2245).
1H nmr(400MHz,CDCl3)δ 8.06(1H,d,J 7.5Hz,NH),8.02(1H,s,トリアゾールH−5),7.39−7.35(3H,m,3×ArH),7.29−7.7.26(2H,m,2×ArH),7.20(2H,m,2×ArH),7.17(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.38(2H,s,NCH 2C6H5),5.12(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.15(2H,t,J 5.5Hz,NCH2CH2Nの2H),3.98,3.93(2H,2d AB系,J 15.5Hz,ArCH2NCH2の2H),3.76(2H,s,ArCH2NCH2の2H),3.42(3H,s,NCH3),2.96(2H,dt,J 4.0,5.5Hz,NCH2CH2Nの2H);19F nmr(380MHz,CDCl3)δ −63.2;m/z:582[M+H]+(実測値[M+H]+,582.2173,C27H26F3N9O3 理論値[M+H]+ 582.2183).
1H nmr(400MHz,CDCl3)δ 8.01(1H,d,J 7.0Hz,NH),7.27−7.19(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.16(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.09(1H,dt,J 10.5,7.5Hz,オキソベンゾオキサザピンH−3),4.70(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.28(1H,dd,J 10.5,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.14(4H,m,NCH2CH2Nの2H),ArCH2NCH2又はCH 2C6H5の2H),3.93(2H,s,ArCH2NCH2又はCH 2C6H5の2H),3.78,3.74(2H,2d AB系,J 13.5Hz,ArCH2NCH2の2H),3.40(3H,s,NCH3),2.97(2H,t,J 5.5Hz,NCH2CH2Nの2H);13C nmr(100MHz,CDCl3)δ 168.8,158.6,152.0,149.6,143.4(q,J 40.0Hz),136.4,135.8,134.3,128.8,128.7,127.9,127.1,126.9,123.4,123.2,118.3(q,J 270.5Hz),77.2,60.8,49.5,49.4,43.6,35.6,33.1;19F nmr(380MHz,CDCl3)δ −63.2;m/z:582[M+H]+(実測値[M+H]+,582.2208,C27H26F3N9O3 理論値[M+H]+ 582.2183).
1H nmr(400MHz,CDCl3)δ 8.04(1H,d,J 7.0Hz,NH),8.01(1H,s,トリアゾールH−5),7.40−7.36(3H,m,C6H5の3H),7.29−7.23(4H,m,C6H5の2H,オキソベンゾオキサザピンH−6,H−8),7.09(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.38(2H,s,NCH 2C6H5),5.06(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.24(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.40(3H,s,NCH3),1.32(9H,s,C(CH3)3);m/z:458[M+H]+(実測値[M+H]+,458.2205,C26H27N5O3 理論値[M+H]+ 458.2187).
1H nmr(400MHz,CDCl3)δ 8.08(1H,d,J 7.5Hz,NH),7.26−7.21(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.07(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.02(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,JHz,オキソベンゾオキサザピンH−2の1H),4.15(2H,s,CH 2C6H5),3.40(3H,s,NCH3),1.32(9H,s,C(CH3)3);13C nmr(100MHz,CDCl3)δ 168.7,158.5,149.2,135.9,135.8,130.9,128.8,128.7,127.0,126.4,122.8,121.8,99.4,77.6,77.2,49.1,35.5,33.2,30.9,27.9;m/z:458[M+H]+(実測値[M+H]+,458.2200,C26H27N5O3 理論値[M+H]+ 458.2187).
1H nmr(400MHz,CDCl3)δ 8.02(1H,d,J 7.5Hz,NH),7.99(1H,s,トリアゾールH−5),7.38−7.34(3H,m,C6H5の3H),7.29−7.25(4H,m,C6H5の2H,オキソベンゾオキサザピンH−6,H−8),7.11(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.36(2H,s,NCH 2C6H5),5.06(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.75(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.25(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.40(3H,s,NCH3),2.55−2.49(2H,m,cBuH−2の2H,H−4),2.33(2H,m,cBuH−2の2H,H−4),1.87(2H,m,cBuH−3);m/z:472[M+H]+,454[M+H−H2O]+(実測値[M+H]+,472.1994,C26H25N5O4 理論値[M+H]+ 472.1979).
1H nmr(400MHz,CDCl3)δ 8.10(1H,d,J 7.5Hz,NH),7.29−7.20(7H,m,C6H5,オキソベンゾオキサザピンH−6の2H,H−8,H−9),7.10(1H,dd,J 7.5,1.0Hz,オキソベンゾオキサザピンH−6の1H,H−8,H−9),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.28(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.15,4.11(2H,2d AB系,J 16.0Hz,CH 2C6H5),3.39(3H,s,NCH3),2.57−2.50(2H,m,cBuH−2の2H,H−4),2.35(2H,m,cBuH−2の2H,H−4),1.92−1.84(2H,m,cBuH−3);13C(100MHz,CDCl3)δ 168.7,158.7,149.9,136.0,135.8,131.0,128.8,128.7,127.0,126.5,123.0,120.4,93.4,81.9,76.9,68.2,49.1,38.5,35.5,33.0,13.0;m/z:454[M+H−H2O]+(実測値[M+H]+,472.1999,C26H25N5O4 理論値[M+H]+ 472.1979).
1H nmr(400MHz,CDCl3)δ 8.02(1H,d,J 7.0Hz,NH),7.99(1H,s,トリアゾールH−5),7.38−7.34(3H,m,C6H5の3H),7.28−7.26(4H,m,C6H5の2H,オキソベンゾオキサザピンH−6,H−8),7.10(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.36(2H,s,NCH2C6H5),5.06(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.75(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.24(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.40(3H,s,NCH3),2.08−1.99(4H,m,cペンタンH−2,H−5),1.90−1.84(2H,m,cペンタンH−3の2H,H−4),1.83−1.76(2H,m,シクロペンタンH−3,H−4の2H);m/z:486[M+H]+,468[M+H−H2O]+(実測値[M+H]+,486.2122,C27H27N5O4 理論値[M+H]+ 486.2136).
1H nmr(400MHz,CDCl3)δ 8.06(1H,d,J 7.5Hz,NH),7.31−7.23(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−7),7.10(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.68(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.14(2H,s,CH 2C6H5),3.39(3H,s,NCH3),2.08−1.97(4H,m,cペンタンH−2,H−5),1.90−1.85(2H,m,cペンタンH−3の2H,H−4),1.82−1.76(2H,m,cペンタンH−3の2H,H−4);m/z:468[M+H−H2O]+(実測値[M+H]+,486.2154,C27H27N5O4 理論値[M+H]+ 486.2136).
1H nmr(400MHz,CDCl3)δ 8.03(1H,d,J 7.0Hz,NH),8.02(1H,s,トリアゾールH−5),7.39−7.35(3H,m,C6H5の3H),7.31−7.27(4H,m,C6H5の2H,オキソベンゾオキサザピンH−6,H−8),7.14(1H,dd,J 8.0,1.0Hz,オキソベンゾオキサザピンH−9),5.37(2H,s,NCH 2C6H5),5.08(1H,dt,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.95(2H,dt,J 12.0,4.5Hz,ピランH−2,H−6の2H),3.72(2H,ddd,J 12.0,9.0,3.0Hz,ピランH−2の2H,H−6),3.42(3H,s,NCH3),2.07−2.02(2H,m,ピランH−3の2H,H−5),1.89(2H,ddd,J 13.0,9.0,4.0Hz,ピランH−3の2H,H−5);m/z:502[M+H]+,484[M+H−H2O]+(実測値[M+H]+,502.2105,C27H27N5O5 理論値[M+H]+ 502.2085).
1H nmr(400MHz,CDCl3)δ 8.07(1H,d,J 6.5Hz,NH),7.28−7.19(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.09(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.00(1H,dt,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),4.64(1H,dd,J 9.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,t,J 10.5Hz,オキソベンゾオキサザピンH−2の1H),4.12(2H,s,CH2C6H5),3.93(2H,dt,J 12.0,4.5Hz,ピランH−2の2H,H−6),3.70(2H,ddd,J 11.5,9.0,2.5Hz,ピランH−2の2H,H−6),3.37(3H,s,NCH3),2.03(2H,m,ピランH−3の2H,H−5),1.88(2H,ddd,J 13.0,9.0,4.0Hz,ピランH−3の2H,H−5);13C nmr(100MHz,CDCl3)δ 168.6,158.7,150.1,136.1,135.7,131.1,128.9,128.8,127.1,126.6,123.2,120.0,92.3,83.4,77.3,66.1,64.8,49.1,39.9,35.6,33.1;m/z:484[M+H−H2O]+(実測値[M+H]+,502.2080,C27H27N5O5 理論値[M+H]+ 502.2085).
1H nmr(400MHz,CDCl3)δ 8.85(1H,d,J 7.5Hz,NH),8.42(1H,d,J 5.5Hz,pyH−6),7.60(1H,d,J 2.5Hz,pyH−3),7.40(2H,m,C6H5の2H),7.27−7.22(3H,m,オキソベンゾオキサザピンH−6,H−8,C6H5の1H),7.10(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),7.05(2H,m,C6H5の2H),6.93(1H,dd,J 5.5,2.5Hz,pyH−5),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.70(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.28(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.41(3H,s,NCH3),1.61(6H,s,C(CH 3)2OH);13C nmr(100MHz,CDCl3)δ 169.0,166.1,163.6,153.7,151.3,150.1,150.0,136.2,130.8,130.3,126.4,125.6,123.0,120.7,120.3,114.4,110.6,94.4,80.7,77.2,65.6,49.3,35.4,31.4;m/z:472[M+H]+(実測値[M+H]+,472.1891,C27H25N3O5 理論値[M+H]+ 472.1867).
1H nmr(400MHz,CDCl3)δ 8.06(1H,d,J 7.5Hz,NH),7.33−7.26(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.14(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.03(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.93(2H,d,J 7.0Hz,オキセタンH−2,H−4の2H),4.80(2H,d,J 7.0Hz,オキセタンH−2の2H,H−4),4.70(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.30(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.16(2H,s,CH 2C6H5),3.41(3H,s,NCH3),2.98(1H,br s,OH);m/z:474[M+H]+(実測値[M+H]+,474.1789,C25H23N5O5 理論値[M+H]+ 474.1772).
1H nmr(400MHz,CDCl3)δ 8.03(1H,d,J 7.0Hz,NH),8.01(1H,s,トリアゾールH−5),7.37(3H,m,C6H5の3H),7.28−7.25(4H,m,C6Hの2H5,オキソベンゾオキサザピンH−6,H−8),7.12(1H,d,J 8.5Hz,オキソベンゾオキサザピンH−9),5.35(2H,s,NCH 2C6H5),5.04(1H,dt,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),4.89(2H,dd,J 7.0,1.0Hz,オキセタンH−2の2H,H−4),4.78(2H,ddd,J 6.5,2.0,1.0Hz,オキソベンゾオキサザピンH−2の2H,H−4),4.72(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.5,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.53(1H,s,OH),3.38(3H,s,NCH3);13C nmr(100MHz,CDCl3)δ 168.7,158.4,156.5,150.4,144.0,136.1,133.7,130.9,129.2,129.0,128.2,126.6,123.4,119.5,88.9,84.5,77.1,67.3,54.4,53.4,49.1,35.5;m/z:474[M+H]+.
1H nmr(400MHz,CDCl3)δ 8.09(1,d,J 7.5Hz,NH),7.27(2H,t,J 7.0Hz,C6H5の2H),7.20−7.15(5H,m,C6H5の3H,オキソベンゾオキサザピンH−6,H−8),7.09(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.41(1H,q,J 1.0Hz,=CH2の1H),5.32(1H,m,=CH2の1H),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.63(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.12(2H,s,CH 2C6H5),3.38(3H,s,NCH3),1.98(3H,t,JHz,C(CH 3)=CH2);13C nmr(100MHz,CDCl3)δ 168.7,158.7,154.6,149.8,136.0,135.9,130.9,128.8,128.7,127.0,126.4(2C),123.1,122.6,121.0,91.3,86.7,77.2,49.2,35.5,33.0,23.3;m/z:464[M+Na]+,442[M+H]+(実測値[M+H]+,442.1869,C25H23N5O3 理論値[M+H]+ 442.1874).
1H nmr(400MHz,CDCl3)δ 8.09(1H,d,J 7.5Hz,NH),7.29−7.19(5H,m,C6H5),7.06(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),7.03(1H,d,J 2.0Hz,オキソベンゾオキサザピンH−6),7.00(1H,m,オキソベンゾオキサザピンH−8),5.04(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.22(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.14(2H,s,CH 2C6H5),3.39(3H,s,NCH3),2.60(2H,m,CH 2CH2CH(CH3)2),1.60(1H,m,CH2CH2CH(CH3)2),1.52−1.46(2H,m,CH2CH 2CH(CH3)2),0.94(6H,d,J 6.5Hz,CH2CH2CH(CH 3)2);m/z:448[M+H]+(実測値[M+H]+,448.2335,C25H29N5O3 理論値[M+H]+ 448.2343).
1H nmr(400MHz,CDCl3)δ 8.09(1H,d,J 7.5Hz,NH),7.28−7.25(2H,m,C6H5の2H),7.19(5H,m,C6H5の3H,オキソベンゾオキサザピンH−6,H−8),7.09(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.63(1H,dd,J 9.0,8.0Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 10.5,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.12(2H,s,CH 2C6H5),3.43(3H,s,NCH3又はOCH3),3.39(3H,s,NCH3又はOCH3),1.54(6H,s,C(CH 3)2OCH3);m/z:474[M+H]+,442[M+H−CH3OH]+(実測値[M+H]+,474.2138,C26H27N5O4 理論値[M+H]+ 474.2136).
1H nmr(400MHz,CDCl3)δ 8.01(1H,d,J 7.5Hz,NH),8.00(1H,s,トリアゾールH−5),7.39−7.34(3H,m,C6H5の3H),7.27−7.23(4H,m,C6H5の2H,オキソベンゾオキサザピンH−8,H−9),7.12(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−6),5.36(2H,s,NCH 2C6H5),5.05(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.73(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.23(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.39(3H,s,NCH3),1.61(6H,s,C(CH 3)2OH);m/z:460[M+H]+,442[M+H−H2O]+(実測値[M+H]+,460.1968,C25H25N5O4 理論値[M+H]+ 460.1979).
1H nmr(400MHz,CDCl3)δ 8.08(1H,d,J 7.5Hz,NH),7.26−7.18(7H,m,C6H5,オキソベンゾオキサザピンH−7,H−9),7.11(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−6),5.00(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.62(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.24(1H,dd,J 11.5,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.14,4.10(2H,2d,J 16.0Hz,CH 2C6H5),3.37(3H,s,NCH3),1.61(6H,s,C(CH 3)2OH);13C nmr(100MHz,CDCl3)δ 168.7,158.7,149.5,136.1,135.9,129.0,128.8,128.7,127.0,126.0,123.1,122.2,95.1,80.6,76.9,65.5,49.2,35.4,33.0,31.4(2C);m/z:442[M+H−H2O]+(実測値[M+H]+,460.1972,C25H25N5O4 理論値[M+H]+ 460.1979).
1H nmr(400MHz,CDCl3)δ 8.83(1H,d,J 7.5Hz,NH),8.42(1H,d,J 5.5Hz,ピリジンH−3),7.60(1H,d,J 2.5Hz,ピリジンH−6),7.42−7.38(2H,m,C6H5の2H),7.28−7.22(3H,m,C6H5の1H,オキソベンゾオキサザピンH−7,H−9),7.13(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−6),7.07−7.04(2H,m,C6H5の2H),6.93(1H,dd,J 5.5,2.5Hz,ピリジンH−4),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.68(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.40(3H,s,NCH3),1.61(6H,s,C(CH 3)2OH);13C nmr(100MHz,CDCl3)δ 169.0,166.1,163.6,153.7,151.3,150.1,149.6,136.4,130.3,128.9,126.0,125.7,123.0,122.0,120.7,114.4,110.6,94.9,80.6,77.2,65.6,49.4,35.3,31.4;m/z:472[M+H]+(実測値[M+H]+,472.1873,C27H25N3O5 理論値[M+H]+ 472.1867).
1H nmr(400MHz,CDCl3)δ 8.05(1H,d,J 7.5Hz,NH),7.33−7.29(3H,m,C6H3Cl2の3H,オキソベンゾオキサザピンH−6),7.226−7.24(1H,m,C6H3Cl2の1H,オキソベンゾオキサザピンH−6),7.18−7.15(1H,m,オキソベンゾオキサザピンH−8)),7.10(1H,d,J 8.5Hz,オキソベンゾオキサザピンH−9),5.00(1H,dt,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),4.67(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.48(2H,s,CH 2C6H3Cl2),4.27(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.39(3H,s,NCH3),1.61(6H,s,C(CH3)2);m/z:532,530,528[M+H]+ 514,512,510[M+H−H2O]+(実測値[M+H]+,528.1201,C25H23Cl2N5O4 理論値[M+H]+ 528.1200).
1H nmr(400MHz,CDCl3)δ 8.04(1H,d,J 7.5Hz,NH),7.30−7.17(8H,m,C6H5,オキソベンゾオキサザピンH−6,H−7,H−9),5.08(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.70(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.30−4.25(3H,m,オキソベンゾオキサザピンH−2の1H,NCH2CH2N),4.14(2H,s,CH2C6H5),3.88,3.83(2H,2d AB系,J 16.0Hz,ArCH2NCH2の2H),3.76(2H,s,ArCH2NCH2),3.40(3H,s,NCH3),3.09−3.02(2H,m,NCH2CH2N);19F nmr(380MHz,CDCl3)δ −65.3;m/z:604[M+Na]+ 582[M+H]+.
1H nmr(400MHz,CDCl3)δ 8.05(1H,d,J 7.0Hz,NH),8.00(1H,s,トリアゾールH−5),7.39−7.35(3H,m,C6H5の3H,オキソベンゾオキサザピンH−6,H−7,H−9),7.28−7.25(2H,m,C6H5の2H,オキソベンゾオキサザピンH−6,H−7,H−9),7.23−7.17(3H,m,C6H5の3H,オキソベンゾオキサザピンH−6,H−7,H−9),5.37(2H,s,NCH 2C6H5),5.11(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.28−4.23(3H,m,オキソベンゾオキサザピンH−2の1H,NCH2CH2Nの2H),3.90,3.86(2H,2d AB系,J 16.0Hz,ArCH2NCH2の2H),3.79,3.75(2H,2d AB系,J 13.5Hz,ArCH2NCH2の2H),3.42(3H,s,NCH3),3.10−3.02(2H,m,NCH2CH2Nの2H);19F nmr(380MHz,CDCl3)δ −65.4;m/z:604[M+Na]+,582[M+H]+.
1H nmr(400MHz,CDCl3)δ 8.85(1H,d,J 7.5Hz,NH),8.43(1H,d,J 5.5Hz,pyH−3),7.60(1H,d,J 2.5Hz,pyH−4),7.42−7.38(2H,m,C6H5の2H),7.27−7.22(3H,m,C6H5の3H,オキソベンゾオキサザピンH−6,H−8),7.11(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),7.10−7.05(2H,m,C6H5の2H,オキソベンゾオキサザピンH−6,H−8),6.93(1H,dd,J 5.5,2.5Hz,pyH−6),5.01(1H,dt,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),4.70(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.28(1H,dd,J 11.5,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.41(3H,s,NCH3);m/z:478[M+H]+,460[M+H−H2O]+(実測値[M+H]+,478.2255,C27H19D6N3O4 理論値[M+H]+ 478.2244).
1H nmr(400MHz,CDCl3)δ 8.09(1H,d,J 7.5Hz,NH),7.28−7.21(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.10(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.14(2H,s,CH 2C6H5),3.39(3H,s,NCH3);13C nmr(100MHz,CDCl3)δ 168.6,158.5,149.9,136.0,135.8,131.0,128.8(2C),127.1(2C),126.5,123.1,120.5,94.6,80.6,77.2,65.3,49.1,35.5,33.2,30.5(m);m/z:466[M+H]+,448[M+H−H2O]+(実測値[M+H]+,466.2356,C25H19D6N5O4 理論値[M+H]+ 466.2356).
1H nmr(400MHz,CDCl3)δ 7.99(1H,d,J 6.5Hz,NH),7.36−7.29(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.13(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),4.97(1H,ddd,J 11.0,7.5,7.0Hz,オキソベンゾオキサザピンH−3),4.72(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,m,オキソベンゾオキサザピンH−2の1H),4.26(2H,s,CH 2C6H5),3.43(3H,s,NCH3),1.63(6H,s,C(CH3)2);m/z:484[M+Na]+,443[M+H−H2O]+(実測値[M+H]+,443.1727,C25H24N4O5 理論値[M+H−H2O]+ 443.1714).
1H nmr(400MHz,CDCl3)δ 8.84(1H,d,J 7.5Hz,NH),8.43(1H,d,J 5.5Hz,pyH−6),7.60(1H,d,J 2.5Hz,pyH−3),7.42−7.39(2H,m,C6H5の2H),7.31(1H,dd,J 8.0,2.0Hz,オキソベンゾオキサザピンH−7),7.27−7.22(2H,m,C6H5の1H,オキソベンゾオキサザピンH−9),7.17(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−6),7.07−7.05(2H,m,C6H5の2H),6.93(1H,dd,J 5.5,2.5Hz,pyH−5),5.02(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.93(2H,d,J 7.0Hz,オキセタンH−2の2H,H−4),4.79(2H,d,J 7.0Hz,オキセタンH−2の2H,H−4),4.69(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.29(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.42(3H,s,NCH3);m/z:486[M+H]+,(実測値[M+H]+,486.1674,C23H23N3O6 理論値[M+H]+ 486.1660).
1H nmr(400MHz,CDCl3)δ 8.07(1H,d,J 7.5Hz,NH),7.97(1H,s,OH),7.32−7.22(6H,m,C6H5,オキソベンゾオキサザピンH−7),7.20(1H,d,J 2.0Hz,オキソベンゾオキサザピンH−9),7.14(1H,d,J 8.5Hz,オキソベンゾオキサザピンH−6の1H),4.99(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.92(2H,d,J 7.0Hz,オキセタンH−2の2H,H−4),4.79(2H,d,J 6.5Hz,オキセタンH−2の2H,H−4),4.64(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.25(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.14(2H,s,CH 2C6H5),3.40(3H,s,NCH3);m/z:474[M+H]+,456[M+H−H2O]+(実測値[M+H]+,474.1784,C25H23N5O5 理論値[M+H]+ 474.1772).
1H nmr(400MHz,CDCl3)δ 8.07(1H,d,J 7.5Hz,NH),8.03(2H,m,COC6H5の2H),7.59(1H,tt,J 7.5,1.0Hz,COC6H5の1H),7.45(2H,t,J 7.5Hz,COC6H5の2H),7.32−7.23(7H,m,CH2C6 H 5,オキソベンゾオキサザピンH−6,H−8),7.12(1H,d,J 8.5Hz,オキソベンゾオキサザピンH−9),5.23(1H,d,J 3.0Hz,イソソルベートH−6),5.02(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.87,4.83(2H,2d AB系,J 4.5Hz,イソソルベートH−3a,H−6a),4.69(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.28(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.25−4.20(2H,m,イソソルベートH−5),4.15(2H,s,CH 2C6H5),4.04,3.95(2H,2d AB系,J 9.5Hz,イソソルベートH−2),3.40(3H,s,NCH3),;m/z:650[M+H]+(実測値[M+H]+,650.2283,C35H31N5O8 理論値[M+H]+ 650.2245).
1H nmr(400MHz,CD3OD)δ 7.51(1H,d,J 2.0Hz,オキソベンゾオキサザピンH−6),7.36(1H,dd,J 8.0,2.0Hz,オキソベンゾオキサザピンH−8),7.33−7.23(5H,m,C6H5),7.19(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.01(1H,dd,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),4.65,4.54(2H,2d AB系,J 4.5Hz,イソソルベートH−3a,H−6a),4.60(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.41(1H,dd,J 11.5,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.24(1H,d,J 2.5Hz,イソソルベートH−6),4.15(2H,s,CH 2C6H5),3.99−3.91(2H,m,イソソルベートH−5の2H),3.93,3.71(2H,2d AB系,J 8.5Hz,イソソルベートH−2),3.40(3H,s,NCH3);13C nmr(100MHz,CD3OD)δ 169.1,150.3,136.5,130.7,128.4,128.3,126.8,126.6,122.7,119.9,110.0,89.5,88.6,87.1,83.7,78.1,77.8,77.5,74.4,49.1,34.4,33.2;m/z:546[M+H]+(実測値[M+H]+,546.2007,C28H27N5O7 理論値[M+H]+ 546.1983).
1H nmr(400MHz,CDCl3)δ 8.06(1H,d,J 7.5Hz,NH),7.31−7.23(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.10(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.02(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.68(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.16(2H,s,CH2C6H5),3.78(3H,s,OCH3),3.41(3H,s,NCH3),1.58(6H,s,C(CH3)2);m/z:502[M+H]+(実測値[M+H]+,502.2107,C27H27N5O4 理論値[M+H]+ 502.2085).
1H nmr(400MHz,CDCl3)δ 7.79(1H,d,J 7.0Hz,NH),7.38−7.32(4H,m,4H又はC6H5,ピラゾールH−4又はH−5,オキソベンゾオキサザピンH−6,H−8),7.28−7.21(4H,m,C6H5,ピラゾールH−4又はH−5,オキソベンゾオキサザピンH−6又はH−8の4H),7.12(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),6.74(1H,d,J 2.5Hz,ピラゾールH−4又はH−5),5.31(2H,s,NCH 2C6H5),5.05(1H,dt,J 11.0,7.0Hz,オキソベンゾオキサザピンH−3),4.73(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.28(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.42(3H,s,NCH3),1.62(6H,s,C(CH 3)2OH);m/z:459[M+H]+,441[M+H−H2O]+(実測値[M+H]+,459.2040,C26H26N4O4 理論値[M+H]+ 459.2027).
1H nmr(400MHz,CDCl3)δ 8.10(1H,d,J 7.0Hz,NH),7.28(2H,m,オキソベンゾオキサザピンH−6,H−8),7.21(1H,m,C6H4Fの1H),7.10(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),7.01(1H,br d,J 8.0Hz,C6H4Fの1H),6.96(1H,br d,J 9.5Hz,C6H4Fの1H),6.90(1H,td,J 8.5,2.5Hz,C6H4Fの1H),5.00(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.29(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.15(2H,s,CH 2C6H4F),3.40(3H,s,NCH3),1.62(6H,s,C(CH 3)2OH);13C nmr(100MHz,CD3OD)δ 168.5,164.0,161.6,149.9,138.5,135.9,131.0,130.2(d,J 8.5Hz),128.8,126.5,124.5(d,J 2.5Hz),123.0,120.5,115.8(d,J 22.0Hz),113.9(d,J 21.5Hz),94.6,80.6,76.9,65.6,49.2,35.5,32.9,31.4;19F nmr(380MHz,CDCl3)δ −112.6;m/z:460[M+H−H2O]+(実測値[M+H]+,478.1901,C25H24FN5O4 理論値[M+H]+ 478.1885).
1H nmr(400MHz,CDCl3)δ 8.11(1H,d,J 7.5Hz,NH),7.27−7.25(2H,m,オキソベンゾオキサザピンH−6,H−8),7.17(2H,dd,J 8.5,5.5Hz,C6H4Fの2H),7.09(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),6.90(2H,t,J 8.5Hz,C6H4Fの2H),4.99(1H,dt,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),4.64(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.29(1H,dd,J 11.5,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.09(2H,s,CH 2C6H4F),3.39(3H,s,NCH3),1.62(6H,s,C(CH 3)2OH);19F nmr(380MHz,CDCl3)δ −115.6;m/z:478[M+H]+ 460[M+H−H2O]+(実測値[M+H]+,478.1902,C25H24FN5O4 理論値[M+H]+ 478.1885).
1H nmr(400MHz,CDCl3)δ 8.08(1H,d,J 7.5Hz,NH),7.26−7.16(3H,m,オキソベンゾオキサザピンH−6,H−8,C6H4Fの1H),7.09(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),7.01(1H,td,J 7.5,1.0Hz,C6H4Fの1H),7.00−6.96(1H,m,C6H4Fの1H),5.00(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.65(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.17(2H,s,CH 2C6H4F),3.38(3H,s,NCH3),1.62(6H,s,C(CH 3)2OH);13C nmr(100MHz,CDCl3)δ 168.7,160.7(d,J 246.3Hz),158.5,149.9,136.0,131.0(d,J 4.0Hz),131.0,129.1,129.0(d,J 8.5Hz),126.5,126.3,124.4(d,J 4.0Hz),123.1,120.4,115.4(d,J 12.0Hz),94.6,80.6,76.9,65.6,49.1,35.5,31.4,26.3;19F nmr(380MHz,CDCl3)δ −117.5;m/z:460[M+H−H2O]+(実測値[M+H]+,478.1895,C25H24FN5O4 理論値[M+H]+ 478.1885).
1H nmr(400MHz,CDCl3)δ 7.40−7.38(6H,m,3×C6H5の2H),7.24−7.20(6H,m,3×C6H5の2H),7.18−7.12(4H,m,3×C6H5の1H,オキソベンゾオキサザピンH−6の1H,H−8,H−9),6.97−6.95(2H,m,オキソベンゾオキサザピンH−6の2H,H−8,H−9),4.48(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.37(1H,dd,J 11.5,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.55(1H,dt,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),3.28(1H,d,J 8.5Hz,NH),2.88(3H,s,NCH3),1.63(6H,s,C(CH 3)2OH);m/z:561[M−H+HCO2H]−.
1H nmr(400MHz,CDCl3)δ 8.09(1H,d,J 7.5Hz,NH),7.33−7.31(2H,m,オキソベンゾオキサザピンH−8,H−9),7.25−7.20(5H,m,C6H5),7.09(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.15(2H,s,CH 2C6H5),3.40(3H,s,NCH3),0.26(9H,s,Si(CH3)3);m/z:474[M+H]+(実測値[M+H]+,474.1981,C25H27N5O3Si 理論値[M+H]+ 474.1956).
1H nmr(400MHz,CDCl3)δ 8.06(1H,d,JHz,NH),7.36(1H,dd,JHz,オキソベンゾオキサザピンH−8),7.35−7.26(6H,m,C6H5,オキソベンゾオキサザピンH−6),7.14(1H,d,J 8.5Hz,オキソベンゾオキサザピンH−9),5.04(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.71(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.29(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.17(2H,s,CH 2C6H5),3.42(3H,s,NCH3),3.12(1H,s,HCC);13C nmr(100MHz,CDCl3)δ 168.6,150.4,136.1,131.5,128.9(2C),127.3,127.0,123.3,119.8,82.0,78.1,77.2,49.1,35.5,33.5;m/z:402[M+H]+(実測値[M+H]+,402.1561,C22H19N5O3 理論値[M+H]+ 402.1576).
1H nmr(400MHz,CDCl3)δ 7.24(1H,d,J 2.0Hz,オキソベンゾオキサザピンH−6),7.22(1H,dd,J 8.0,2.0Hz,オキソベンゾオキサザピンH−8),7.06(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),4.41(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.12(1H,dd,J 11.5,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.72(1H,dd,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3);m/z:275[M+H]+(実測値[M+H]+,275.1390,C15H18N2O3 理論値[M+H]+ 275.1404).
1H nmr(400MHz,CDCl3)δ 8.03(1H,d,J 7.0Hz,NH),7.83(1H,s,トリアゾールH−5),7.32−7.21(5H,m,C6H4の5H,オキソベンゾオキサザピンH−6),7.16(1H,dd,J 9.0,2.0Hz,オキソベンゾオキサザピンH−8),7.12(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.37(2H,s,NCH 2C6H4CH3),5.07(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.41(3H,s,NCH3),2.27(3H,s,C6H4CH 3),1.62(6H,s,C(CH 3)2OH);13C nmr(100MHz,CDCl3)δ 168.8,158.4,156.5,149.9,143.8,136.8,136.0,131.4,131.1,130.9,129.7,129.4,126.8,126.5,123.2,120.4,94.5,80.6,77.1,65.5,52.6,49.1,35.5,31.4,19.0;m/z:474[M+H]+,456[M+H−H2O]+
1H nmr(400MHz,CDCl3)δ 8.07(1H,s,トリアゾールH−5),8.06(1H,d,J 7.0Hz,NH),7.60−7.55(4H,m,C6H4C6H5の4H),7.45−7.42(2H,m,C6H4C6H5の2H),7.38−7.34(3H,m,C6H4C6H5の3H),7.28−7.26(2H,m,オキソベンゾオキサザピンH−6,H−8),7.11(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.41(2H,s,NCH 2C6H4Ph),5.07(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.41(3H,s,NCH3),1.62(6H,s,C(CH 3)2OH);13C nmr(100MHz,CDCl3)δ 169.1,158.7,157.0,150.3,144.3,142.3,140.4,136.3,132.9,131.2,129.2,129.0,128.2,128.0,127.4,126.8,123.5,120.7,94.9,80.9,77.5,65.9,54.4,49.4,35.8,31.7;m/z:536[M+H]+,518[M+H−H2O]+
1H nmr(400MHz,CDCl3)δ 8.02(1H,d,J 7.0Hz,NH),7.59(1H,s,トリアゾールH−5),7.28−7.21(3H,m,オキソベンゾオキサザピンH−6の3H,H−8,H−9,C6 H 3(CH3)2),7.13−7.10(3H,m,オキソベンゾオキサザピンH−6の3H,H−8,H−9,C6H3(CH 3)2),5.41(2H,s,NCH 2C6H3(CH3)2),5.06(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,9.5Hz,オキソベンゾオキサザピンH−2の1H),3.41(3H,s,NCH3),2.30(6H,s,C6H3(CH 3)2),1.62(6H,s,C(CH 3)2OH);13C nmr(100MHz,CDCl3)δ 168.8,158.5,156.5,149.9,143.1,138.1,136.0,130.9,129.6,129.0(2C),126.5,123.2,120.4,94.5,80.6,77.1,65.5,49.1,49.0,35.5,31.4,19.6;m/z:488[M+H]+,470[M+H−H2O]+(実測値[M+H]+,488.2292,C27H29N5O4 理論値[M+H]+ 488.2292).
1H nmr(400MHz,CDCl3)δ 8.04(1H,s,トリアゾールH−5),8.03(1H,d,J 7.0Hz,NH),7.29−7.26(2H,m,オキソベンゾオキサザピンH−6,H−8),7.12(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.06(1H,ddd,J 11.0,7.5,7.0Hz,オキソベンゾオキサザピンH−3),4.75(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.98(2H,d,J 7.0Hz,NCH 2CH(CH3)2),3.41(3H,s,NCH3),2.30−2.23(1H,m,CH(CH3)2),1.62(6H,s,C(CH 3)2OH),0.91(6H,dd,J 6.5,1.0Hz,CH(CH 3)2);13C nmr(100MHz,CDCl3)δ 168.9,158.5,156.5,149.9,144.3,136.0,130.9,126.5,123.2,120.4,94.5,80.6,77.1,65.5,57.6,49.1,35.5,31.4,29.0,19.7;m/z:426[M+H]+,408[M+H−H2O]+(実測値[M+H]+,426.2126,C22H27N5O4 理論値[M+H]+ 426.2136).
1H nmr(400MHz,CDCl3)δ 7.30−7.18(5H,m, C6H5の5H,オキソベンゾオキサザピンH−6,H−8,H−9),7.13−7.06(3H,m,C6H5の3H,オキソベンゾオキサザピンH−6,H−8,H−9),6.85−6.77(0.66H,m,オキソベンゾオキサザピンH−3メジャー),5.34−5.27(0.33H,m,オキソベンゾオキサザピンH−3マイナー),4.94(0.33H,dd,J 12.0,10.5Hz,オキソベンゾオキサザピンH−3マイナー),4.84(0.66H,dd,J 12.0,9.5Hz,オキソベンゾオキサザピンH−3メジャー),4.55(0.66H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2メジャーの1H),4.50(0.33H,m,オキソベンゾオキサザピンH−2マイナーの1H),4.11(0.66H,s,CH 2C6H5マイナー),4.05(1.32H,q,J 7.0Hz,NCH 2CH3メジャー),3.91,3.84(1.32H,2d AB系,J 15.5Hz,CH 2C6H5メジャー),3.50(0.66H,q,J 7.0Hz,NCH 2CH3マイナー),3.28(1H,s,NCH3マイナー),3.25(2H,s,NCH3メジャー),1.61(2H,s,C(CH3)2OHマイナー),1.57(4H,s,C(CH3)2OHメジャー),1.20(3H,t,J 7.0Hz,NCH2CH 3);m/z:488[M+H]+,470[M+H−H2O]+(実測値[M+H]+,488.2291,C27H29N5O4 理論値[M+H]+ 488.2292).
1H nmr(400MHz,CDCl3)δ 8.10(1H,d,JHz,NH),7.33(1H,m,オキソベンゾオキサザピンH−6),7.31(1H,dd,J 8.0,2.5Hz,オキソベンゾオキサザピンH−8),7.15(5H,br s,C6H5),7.02(1H,dd,J 8.0,1.0Hz,オキソベンゾオキサザピンH−9),4.10(2H,s,CH 2C6H5),3.36(3H,s,NCH3);13C(100MHz,100MHz)δ 168.7,158.9,149.1,137.4,135.8,130.6,128.8,128.7,127.1,126.4,118.1,77.2,49.2,35.5,32.9;m/z:458,456[M+H]+(実測値[M+H]+,458.0651,C20H18BrN5O3 理論値[M+H]+ 458.0645).
1H nmr(400MHz,CDCl3)δ 7.72(1H,d,J 7.0Hz,NH),7.36−7.21(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.11(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),6.30(1H,br s,イソオキサゾールH−5),4.99(1H,dt,J 11.0,7.0Hz,オキソベンゾオキサザピンH−3),4.70(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.10(2H,s,CH 2C6H5),3.41(3H,s,NCH3),1.62(6H,s,C(CH 3)2OH);13C nmr(100MHz,CDCl3)δ 174.1,168.4,158.5,157.9,149.9,136.0,135.2,130.9,128.9,128.7,127.4,126.5,123.1,120.4,101.6,94.6,80.6,76.9,65.6,49.2,35.5,33.2,31.4,;m/z:460[M+H]+,442[M+H−H2O]+(実測値[M+H]+,460.1884,C26H25N3O5 理論値[M+H]+ 460.1867).
1H nmr(400MHz,CD3OD)δ 7.71(1H,dd,J 5.5,3.0Hz,1×ArH),7.20(1H,dd,J 5.5,3.0Hz,1×ArH),7.59(1H,d,J 2.0Hz,1×ArH),7.44(1H,td,J 8.5,2.0Hz,1×ArH),7.41(1H,br s,1×ArH),7.33−7.23(6H,m,6×ArH),5.03(1H,dd,J 11.5,7.5Hz,オキソベンゾオキサザピンH−3),4.60(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.45(1H,dd,J 11.5,9.5Hz,オキソベンゾオキサザピンH−2の1H),4.35(2H,s,イソキノリンH−1),4.16(2H,s CH2C6H5),3.50(2H,t,J 6.5Hz,イソキノリンH−3又はH−4),3.42(3H,s,NCH3),3.13(2H,dd,J 7.0,6.0Hz,イソキノリンH−3又はH−4);m/z:533[M+H]+(実測値[M+H]+,533.2296,C31H28N6O3 理論値[M+H]+ 533.2296).
1H nmr(400MHz,CDCl3)δ 8.07(1H,d,J 7.0Hz,NH),7.26−7.19(4H,m,オキソベンゾオキサザピンH−6,H−7,C6H4Fの2H),7.08(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),7.06−7.02(1H,m,C6H4Fの1H),7.03−6.99(1H,m,C6H4Fの1H),5.01(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 10.0,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.25(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.19(2H,s,CH 2C6H4F),3.40(3H,s,NCH3),1.32(9H,s,C(CH3)3);13C nmr(100MHz,CDCl3)δ 168.8,160.7(d,J 245.5Hz),158.5,149.2,135.8,131.0(d,J 4.0Hz),130.9,128.9(d,J 8.5Hz),126.4,124.3(d,J 4.0Hz),123.1(d,J 15.0Hz),122.8,121.8,115.3(d,J 21.5Hz),99.4,77.6,77.0,49.2,35.5,30.9,27.9,26.3;m/z:476[M+H]+(実測値[M+H]+,476.2100,C25H26FN5O3 理論値[M+H]+ 476.2092).
1H nmr(400MHz,CDCl3)δ 8.02(1H,d,J 7.5Hz,NH),7.59(1H,s,トリアゾールH−5),7.26−7.22(3H,m,オキソベンゾオキサザピンH−6,H−8,C6H3(CH3)2H−4),7.12(2H,d,J 7.5Hz,C6H3(CH3)2H−3,H−5),7.09(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.42(2H,s,NCH 2C6H3(CH3)2),5.06(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.24(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),3.42(3H,s,NCH3),2.31(6H,s,C6H3(CH3)2,1.32(9H,s,C(CH3)3);m/z:486[M+H]+(実測値[M+H]+,486.2506,C28H31N5O3 理論値[M+H]+ 486.2500).
1H nmr(400MHz,CDCl3)δ 8.08(1H,d,J 7.5Hz,NH),7.33−7.26(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.12(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),4.99(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.21−4.11(1H,m,NCH 2CH3の1H),4.16(2H,s,NCH 2C6H5),3.66(1H,heptet,J 7.0Hz,NCH 2CH3の1H),1.63(6H,s,C(CH 3)2OH),1.19(3H,t,J 7.0Hz,NCH2CH 3);m/z:456[M+H−H2O]+(実測値[M+H]+,474.2143,C26H27N5O4 理論値[M+H]+ 474.2136).
1H nmr(400MHz,CDCl3)δ 8.09(1H,d,J 7.5Hz,NH),7.30−7.28(2H,m,オキソベンゾオキサザピンH−6,H−8),7.26−7.21(1H,m,C6H4Fの1H),7.12(1H,d,J 8.5Hz,オキソベンゾオキサザピンH−9),7.03(1H,br d,J 7.5Hz,C6H4Fの1H),6.98(1H,br d,J 9.5Hz,C6H4Fの1H),6.92(1H,td,J 8.5,2.5Hz,C6H4Fの1H),4.97(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.65(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,dd,J 11.0,10.5Hz,オキソベンゾオキサザピンH−2の1H),4.22−4.10(1H,m,NCH 2CH3の1H),4.14(2H,s,CH 2C6H4F),3.66(1H,heptet,J 7.0Hz,NCH 2CH3の1H),1.63(6H,s,C(CH 3)2OH),1.19(3H,t,J 7.0Hz,NCH2CH 3);19F nmr(380MHz,CDCl3)δ −112.6;m/z:474[M+H−H2O]+(実測値[M+H]+,492.2047,C26H26FN5O4 理論値[M+H]+ 492.2042).
1H nmr(400MHz,CDCl3)δ 8.01(1H,d,J 7.0Hz,1×NH),7.54(1H,s,1×NH),7.35−7.24(6H,m,C5H5,オキソベンゾオキサザピンH−8),7.10(1H,d,J 8.5Hz,オキソベンゾオキサザピンH−9),7.09(1H,m,オキソベンゾオキサザピンH−6),5.40(1H,br s,C=CH2の1H),5.32(1H,br s,C=CH2の1H),5.08(1H,m,オキソベンゾオキサザピンH−3),4.76(1H,dd,J 10.0,6.0Hz,オキソベンゾオキサザピンH−2の1H),4.33(1H,t,J 10.5Hz,オキソベンゾオキサザピンH−2の1H),4.18(2H,s,CH 2C6H5),1.98(3H,s,CCH3);m/z:428[M+H]+(実測値[M+H]+,428.1709,C24H21N5O3 理論値[M+H]+ 428.1717).
1H nmr(400MHz,CD3OD)δ 7.32−7.21(7H,m,C6H5,オキソベンゾオキサザピンH−6,H−8),7.06(1H,d,J 8.0Hz,オキソベンゾオキサザピンH−9),5.00(1H,dd,J 10.5,6.5Hz,オキソベンゾオキサザピンH−3),4.61(1H,dd,J 10.5,6.5Hz,オキソベンゾオキサザピンH−2の1H),4.40(1H,t,J 9.5Hz,オキソベンゾオキサザピンH−2の1H),4.15(2H,s,CH2C6H5);m/z:444,442[M+H]+(実測値[M+H]+,444.0492,C19H16BrN5O3 理論値[M+H]+ 444.0489).
1H nmr(400MHz,CDCl3)δ 8.07(1H,d,J 7.5Hz,NH),7.28−7.20(7H,m,オキソベンゾオキサザピンH−6,H−8,C6H5),7.09(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.02(1H,dt,J 11.0,7.5Hz,オキソベンゾオキサザピンH−3),4.66(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.26(1H,dd,J 11.0,10.0Hz,オキソベンゾオキサザピンH−2の1H),4.14(2H,s,CH 2C6H5),3.62(2H,s,CCH2N),3.38(3H,s,NCH3),2.73−2.70(4H,m,ピロリジンの4H),1.86−1.82(4H,m,ピロリジンの4H);m/z:485[M+H]+(実測値[M+H]+,485.2322,C27H28N6O3 理論値[M+H]+ 485.2296).
1H nmr(400MHz,CDCl3)δ 8.08(1H,d,J 7.0Hz,NH),7.29−7.7.27(2H,m,オキソベンゾオキサザピンH−6,H−8),7.25−7.18(5H,m,C6H5),7.10(1H,d,J 9.0Hz,オキソベンゾオキサザピンH−9),5.02(1H,dt,J 11.0,7.0Hz,オキソベンゾオキサザピンH−3),4.65(1H,dd,J 9.5,7.5Hz,オキソベンゾオキサザピンH−2の1H),4.27(1H,t,J 10.5Hz,オキソベンゾオキサザピンH−2の1H),4.13(2H,s,CH 2C6H5),3.78,3.76(4H,2d AB系,J 4.5Hz,モルホリンの4H),3.50(2H,s,CCH2N),3.39(3H,s,NCH3),2.65,2.63(4H,2d AB系,J 4.5Hz,モルホリンの4H);m/z:501[M+H]+(実測値[M+H]+,501.2245,C27H28N6O4 理論値[M+H]+ 501.2245).
本実施例では、ADP-Glo(商標)技術を用いる生化学分析により開示化合物を評価した。
本実施例では、U937及びL929細胞を本開示化合物に曝露して細胞ネクロプトーシスアッセイを行うことにより、化合物のヒトRIP1及びマウスRIP1に対する活性を評価した。
本実施例では、急性低体温症マウスモデル試験を用いて、本明細書に開示する化合物がTNFαにより惹起される低体温症を阻害する能力を評価した。
Claims (20)
- 式
環Bは、5員環又は6員環のヘテロアリールであり;
Lは、ヘテロ原子又はRaであり、但し、Raは、H又はDではなく;
Zは、C1〜10脂肪族(C1〜10アルキル、C2〜10アルケニル、C2〜10アルキニル若しくはC3〜6シクロアルキルなど);又は
R1は、ハロゲン、−C≡CH又は−リンカー−R6基であり、リンカーは、Raであり、但し、Raは、H又はDではなく、及びR6は、Rb、−C(Rf)3又は−C(Rf)=C(Rf)2であり;
R2及びR3は、独立に、Raであり;
R4及びR5は、独立に、Reであり;
Raは、それぞれの場合に独立に、H、D、C1〜10脂肪族、C1〜10ハロ脂肪族、C5〜10芳香族又はC3〜6複素環であり;
Rbは、それぞれの場合に独立に、−OH、−SH、−ORc、−SRc、−NRdRd、−Si(Ra)3、−C(O)OH、−C(O)ORc又は−C(O)NRdRdであり;
Rcは、それぞれの場合に独立に、C1〜10アルキル、C2〜10アルケニル、C2〜10アルキニル、C3〜6シクロアルキル又はC5〜10芳香族であり;
Rdは、それぞれの場合に独立に、H;C1〜6アルキル;C3〜6シクロアルキル;C3〜6複素環;C5〜10アリール;C5〜10ヘテロアリールであるか;又は2個のRd基は、それらが結合されている窒素と一緒になって、C3〜9複素環若しくはC5〜10ヘテロアリールを提供し;
Reは、それぞれの場合に独立に、ハロゲン、C1〜6アルキル、C2〜10アルケニル、C2〜10アルキニル、C1〜6ハロアルキル、C3〜6シクロアルキル、C5〜10ヘテロアリール又は−ORaであり;
Rfは、それぞれの場合に独立に、Ra、Rb若しくはReであるか、又は2個のRf基は、それらが結合されている炭素原子と一緒になって、C3〜6シクロアルキル基若しくはC3〜10複素環を提供し;
mは、1〜4であり;
nは、0、1又は2であり;及び
pは、0、1、2、3、4又は5である)
を有する化合物又はその医薬的に許容される塩。 - 環Bは、ジアゾール、トリアゾール、オキサジアゾール、オキサゾール又はピリジニルである、請求項1〜4のいずれか一項に記載の化合物。
- R5は、Reであり、Reは、ハロゲン又はメチルである、請求項1〜6のいずれか一項に記載の化合物。
- 前記リンカー−R6基の前記リンカーは、Raであり、Raは、アルキル、アルケニル又はアルキニル基を含むC1、C2、C3又はC4脂肪族基である、請求項1〜7のいずれか一項に記載の化合物。
- 前記C2基は、アルキンを含み、R6は、Rbであり、Rbは、−C(Rf)3であり、1個のRfは、Reであり、及びそれぞれの他のRfは、それぞれの場合に独立に、Raであり、Raは、C1〜4アルキルである、請求項8に記載の化合物。
- Reは、−ORaであり、Raは、Hである、請求項9に記載の化合物。
- Raは、メチルである、請求項9又は10に記載の化合物。
- 請求項1〜15のいずれか一項に記載の化合物、添加剤、治療薬又はこれらの組合せを含む医薬組成物。
- 受容体相互作用タンパク質−1(RIP1)キナーゼを、請求項1〜15のいずれか一項に記載の化合物又は請求項16に記載の医薬組成物と接触させることを含む方法。
- 対象の疾患を治療するための方法であって、前記対象に、(i)治療有効量の、請求項1〜15のいずれか一項に記載の化合物又はその医薬的に許容される塩、立体異性体、N−オキシド、互変異性体、水和物、溶媒和物、同位体若しくはプロドラッグ;或いは(ii)治療有効量の、請求項16に記載の医薬組成物を投与することを含み、前記対象は、前記疾患を有するか又はそれを有するか若しくは発症する疑いがあり、前記疾患は、受容体相互作用タンパク質−1(RIP1)キナーゼが関与する疾患である、方法。
- 請求項1〜15のいずれか一項に記載の化合物を製造するための方法であって
式Aを有する出発物質を、R1を含有する試剤であって、R1は、リンカー−R6基を含む、R1を含有する試剤と、前記出発物質及び前記R1を含有する試剤を遷移金属触媒、塩基及び溶媒と組み合わせることによってカップリングさせて、官能基化された生成物を生成することと;
前記官能基化された生成物のアミン基を脱保護して、アミン化合物を提供することと;
前記アミン化合物と、酸を含有するカップリング相手との間にアミド結合を形成して、アミド含有化合物を提供することと
を含み、
式Aは、
前記官能基化された生成物は、式B
前記酸を含有するカップリング相手は、式C
Xは、ハロゲン又はトリフラートであり;
PGは、アミン保護基であり;及び
環B、L、R1、R2、R4、R5、m、n及びpのそれぞれは、請求項1〜15のいずれか一項に記載の通りである、方法。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2022160665A (ja) * | 2018-05-03 | 2022-10-19 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Rip1阻害剤化合物並びにそれを製造及び使用するための方法 |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2947446T3 (es) | 2018-05-03 | 2023-08-09 | Rigel Pharmaceuticals Inc | Compuestos inhibidores de RIP1 y métodos para fabricar y usar los mismos |
JP7045526B2 (ja) * | 2018-11-02 | 2022-03-31 | 中国科学院上海薬物研究所 | Rip1キナーゼを阻害する複素環状アミド及びその使用 |
CN111138448B (zh) * | 2018-11-02 | 2022-08-02 | 中国科学院上海药物研究所 | 抑制rip1激酶的杂环酰胺及其用途 |
US11718612B2 (en) | 2019-09-06 | 2023-08-08 | Board Of Regents, The University Of Texas System | Inhibitors of receptor interacting protein kinase I for the treatment of disease |
AU2020341681B2 (en) * | 2019-09-06 | 2024-02-15 | Rigel Pharmaceuticals, Inc. | RIP1 inhibitory compounds and methods for making and using the same |
CR20220075A (es) * | 2019-09-06 | 2022-07-14 | Rigel Pharmaceuticals Inc | Compuestos inhibidores de rip1 y métodos para prepararlos y usarlos |
MX2022003671A (es) | 2019-09-27 | 2022-04-25 | Univ Texas | Inhibidores de proteina cinasa i de interaccion con receptores para el tratamiento de enfermedades. |
WO2021080757A1 (en) * | 2019-10-21 | 2021-04-29 | Google Llc | Verifiable consent for privacy protection |
US11578078B2 (en) | 2019-11-07 | 2023-02-14 | Rigel Pharmaceuticals, Inc. | Heterocyclic RIP1 inhibitory compounds |
WO2021108198A1 (en) * | 2019-11-26 | 2021-06-03 | Board Of Regents, The University Of Texas System | Inhibitors of receptor interacting protein kinase i for the treatment of disease |
CN115515940A (zh) * | 2020-02-28 | 2022-12-23 | 德州大学系统董事会 | 用于治疗疾病的受体相互作用蛋白激酶i的抑制剂 |
AR121717A1 (es) | 2020-04-02 | 2022-06-29 | Rigel Pharmaceuticals Inc | Inhibidores de rip1k |
AR122703A1 (es) | 2020-07-01 | 2022-09-28 | Rigel Pharmaceuticals Inc | Inhibidores de rip1k |
WO2022171111A1 (en) * | 2021-02-10 | 2022-08-18 | Zai Lab (Us) Llc | Heteroaryl-fused bicyclic compound as rip1-kinase inhibitors and uses thereof |
CN114989156A (zh) * | 2021-05-19 | 2022-09-02 | 成都贝诺科成生物科技有限公司 | 一种受体相互作用蛋白抑制剂及其制备方法和用途 |
CN117460722A (zh) | 2021-08-10 | 2024-01-26 | 艾伯维公司 | 烟酰胺ripk1抑制剂 |
WO2023114061A1 (en) | 2021-12-16 | 2023-06-22 | Rigel Pharmaceuticals, Inc. | Crystalline forms of a ripk1 inhibitor |
CN116478150A (zh) * | 2022-01-21 | 2023-07-25 | 中国科学院上海药物研究所 | 具有ripk1抑制活性的化合物、其制备方法及其用途 |
CN114736197B (zh) * | 2022-06-13 | 2022-09-13 | 南京医工医药技术有限公司 | 咪唑啉酮衍生物及其用途 |
CN115353513A (zh) * | 2022-07-29 | 2022-11-18 | 中国人民解放军海军军医大学 | 一种抑制程序性细胞坏死的硫代七元环衍生物及其应用 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014125444A1 (en) * | 2013-02-15 | 2014-08-21 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides as kinase inhibitors |
JP2017524028A (ja) * | 2014-08-21 | 2017-08-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 薬剤としてのrip1キナーゼ阻害剤である複素環式アミド |
JP2018519319A (ja) * | 2015-07-02 | 2018-07-19 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 二環式ラクタム及びその使用方法 |
JP2019530726A (ja) * | 2016-10-17 | 2019-10-24 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 二環式ピリドンラクタム及びその使用方法。 |
JP2020509009A (ja) * | 2017-02-27 | 2020-03-26 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | キナーゼ阻害剤としての複素環式アミド |
JP2021523225A (ja) * | 2018-05-03 | 2021-09-02 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Rip1阻害剤化合物並びにそれを製造及び使用するための方法 |
Family Cites Families (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4921475A (en) | 1983-08-18 | 1990-05-01 | Drug Delivery Systems Inc. | Transdermal drug patch with microtubes |
US5087240A (en) | 1983-08-18 | 1992-02-11 | Drug Delivery Systems Inc. | Transdermal drug patch with conductive fibers |
US4738851A (en) | 1985-09-27 | 1988-04-19 | University Of Iowa Research Foundation, Inc. | Controlled release ophthalmic gel formulation |
US5163899A (en) | 1987-03-20 | 1992-11-17 | Drug Delivery Systems Inc. | Transdermal drug delivery system |
US5312325A (en) | 1987-05-28 | 1994-05-17 | Drug Delivery Systems Inc | Pulsating transdermal drug delivery system |
GB8804164D0 (en) | 1988-02-23 | 1988-03-23 | Tucker J M | Bandage for administering physiologically active compound |
US4882150A (en) | 1988-06-03 | 1989-11-21 | Kaufman Herbert E | Drug delivery system |
US5008110A (en) | 1988-11-10 | 1991-04-16 | The Procter & Gamble Company | Storage-stable transdermal patch |
US5088977A (en) | 1988-12-21 | 1992-02-18 | Drug Delivery Systems Inc. | Electrical transdermal drug applicator with counteractor and method of drug delivery |
US5521222A (en) | 1989-09-28 | 1996-05-28 | Alcon Laboratories, Inc. | Topical ophthalmic pharmaceutical vehicles |
ES2055280T3 (es) | 1989-12-04 | 1994-08-16 | Searle & Co | Sistema monocapa para la administracion transdermica de farmacos. |
US5077033A (en) | 1990-08-07 | 1991-12-31 | Mediventures Inc. | Ophthalmic drug delivery with thermo-irreversible gels of polxoxyalkylene polymer and ionic polysaccharide |
JP2594486B2 (ja) | 1991-01-15 | 1997-03-26 | アルコン ラボラトリーズ インコーポレイテッド | 局所的眼薬組成物 |
US5352456A (en) | 1991-10-10 | 1994-10-04 | Cygnus Therapeutic Systems | Device for administering drug transdermally which provides an initial pulse of drug |
CA2123809A1 (en) | 1991-12-18 | 1993-06-24 | Debra L. Wilfong | Multilayered barrier structures |
ATE132381T1 (de) | 1992-01-29 | 1996-01-15 | Voelkl Franz Ski | Ballspielschläger, insbesondere tennisschläger |
IL114193A (en) | 1994-06-20 | 2000-02-29 | Teva Pharma | Ophthalmic pharmaceutical compositions based on sodium alginate |
ES2094688B1 (es) | 1994-08-08 | 1997-08-01 | Cusi Lab | Manoemulsion del tipo de aceite en agua, util como vehiculo oftalmico y procedimiento para su preparacion. |
IT1283911B1 (it) | 1996-02-05 | 1998-05-07 | Farmigea Spa | Soluzioni oftalmiche viscosizzate con polisaccaridi della gomma di tamarindo |
US5800807A (en) | 1997-01-29 | 1998-09-01 | Bausch & Lomb Incorporated | Ophthalmic compositions including glycerin and propylene glycol |
US6261547B1 (en) | 1998-04-07 | 2001-07-17 | Alcon Manufacturing, Ltd. | Gelling ophthalmic compositions containing xanthan gum |
US6197934B1 (en) | 1998-05-22 | 2001-03-06 | Collagenesis, Inc. | Compound delivery using rapidly dissolving collagen film |
EP2192838A4 (en) | 2007-08-15 | 2011-07-27 | Harvard College | HETEROCYCLIC NEKROPTOSIS HEMMER |
JP2016514693A (ja) | 2013-03-15 | 2016-05-23 | プレジデント アンド フェローズ オブ ハーバード カレッジ | ハイブリッド型ネクロトーシス阻害剤 |
JP2018505199A (ja) | 2015-02-13 | 2018-02-22 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | (S)−5−ベンジル−N−(5−メチル−4−オキソ−2,3,4,5テトラヒドロベンゾ[b][1,4]オキサゼピン−3−イル)−4H−1,2,4−トリアゾール−3−カルボキサミドの結晶形 |
DK3362449T3 (da) | 2015-10-13 | 2021-07-19 | Inst Nat Sante Rech Med | Sibirilin-derivater til anvendelse til at forebygge og/eller behandle lidelser associeret med cellulær nekroptose |
JP6754772B2 (ja) | 2015-10-23 | 2020-09-16 | 武田薬品工業株式会社 | 複素環化合物 |
WO2017109724A1 (en) | 2015-12-21 | 2017-06-29 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides as kinase inhibitors |
KR20180114910A (ko) | 2016-02-05 | 2018-10-19 | 데날리 테라퓨틱스 인크. | 수용체-상호작용 단백질 키나제 1의 억제제 |
US11072607B2 (en) | 2016-12-16 | 2021-07-27 | Genentech, Inc. | Inhibitors of RIP1 kinase and methods of use thereof |
JP2021523226A (ja) * | 2018-05-03 | 2021-09-02 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Rip1阻害剤化合物並びにそれを製造及び使用するための方法 |
JP2022511213A (ja) | 2018-06-26 | 2022-01-31 | シャンハイ インスティテュート オブ オーガニック ケミストリー,チャイニーズ アカデミー オブ サイエンシズ | 細胞壊死阻害剤、その調製方法およびその使用 |
CN111138448B (zh) | 2018-11-02 | 2022-08-02 | 中国科学院上海药物研究所 | 抑制rip1激酶的杂环酰胺及其用途 |
JP7045526B2 (ja) | 2018-11-02 | 2022-03-31 | 中国科学院上海薬物研究所 | Rip1キナーゼを阻害する複素環状アミド及びその使用 |
AU2020341681B2 (en) | 2019-09-06 | 2024-02-15 | Rigel Pharmaceuticals, Inc. | RIP1 inhibitory compounds and methods for making and using the same |
-
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Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014125444A1 (en) * | 2013-02-15 | 2014-08-21 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides as kinase inhibitors |
JP2016512488A (ja) * | 2013-02-15 | 2016-04-28 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | キナーゼ阻害剤としての複素環式アミド |
JP2017524028A (ja) * | 2014-08-21 | 2017-08-24 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | 薬剤としてのrip1キナーゼ阻害剤である複素環式アミド |
JP2018519319A (ja) * | 2015-07-02 | 2018-07-19 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 二環式ラクタム及びその使用方法 |
JP2019530726A (ja) * | 2016-10-17 | 2019-10-24 | エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft | 二環式ピリドンラクタム及びその使用方法。 |
JP2020509009A (ja) * | 2017-02-27 | 2020-03-26 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | キナーゼ阻害剤としての複素環式アミド |
JP2021523225A (ja) * | 2018-05-03 | 2021-09-02 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Rip1阻害剤化合物並びにそれを製造及び使用するための方法 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2022160665A (ja) * | 2018-05-03 | 2022-10-19 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Rip1阻害剤化合物並びにそれを製造及び使用するための方法 |
JP7187729B2 (ja) | 2018-05-03 | 2022-12-12 | ライジェル ファーマシューティカルズ, インコーポレイテッド | Rip1阻害剤化合物並びにそれを製造及び使用するための方法 |
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