JPWO2007125952A1 - Npyy5受容体拮抗作用を有するアミン誘導体 - Google Patents
Npyy5受容体拮抗作用を有するアミン誘導体 Download PDFInfo
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- JPWO2007125952A1 JPWO2007125952A1 JP2008513237A JP2008513237A JPWO2007125952A1 JP WO2007125952 A1 JPWO2007125952 A1 JP WO2007125952A1 JP 2008513237 A JP2008513237 A JP 2008513237A JP 2008513237 A JP2008513237 A JP 2008513237A JP WO2007125952 A1 JPWO2007125952 A1 JP WO2007125952A1
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- 0 *c1cnc(*)cc1 Chemical compound *c1cnc(*)cc1 0.000 description 25
- IIEWJVIFRVWJOD-UHFFFAOYSA-N CCC1CCCCC1 Chemical compound CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 4
- UAEPNZWRGJTJPN-UHFFFAOYSA-N CC1CCCCC1 Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
- CQZJBZRPDGMPPB-QEXXYFSFSA-O CC(C)(C)S(N[C@H]1CC[C@@](C)(CNC(C2)C=CC=C2c2ccccn2)CC1)(O)[OH2+] Chemical compound CC(C)(C)S(N[C@H]1CC[C@@](C)(CNC(C2)C=CC=C2c2ccccn2)CC1)(O)[OH2+] CQZJBZRPDGMPPB-QEXXYFSFSA-O 0.000 description 1
- QRMPKOFEUHIBNM-UHFFFAOYSA-N CC1CCC(C)CC1 Chemical compound CC1CCC(C)CC1 QRMPKOFEUHIBNM-UHFFFAOYSA-N 0.000 description 1
- HPNSNOXSCJYLHE-UHFFFAOYSA-N CCC(C(C)O)NCC1CCCCC1 Chemical compound CCC(C(C)O)NCC1CCCCC1 HPNSNOXSCJYLHE-UHFFFAOYSA-N 0.000 description 1
- QMMUYVTYTBICLS-UHFFFAOYSA-N CCC(CC1)CCC1NC Chemical compound CCC(CC1)CCC1NC QMMUYVTYTBICLS-UHFFFAOYSA-N 0.000 description 1
- CYISMTMRBPPERU-UHFFFAOYSA-N CCC1CCC(C)CC1 Chemical compound CCC1CCC(C)CC1 CYISMTMRBPPERU-UHFFFAOYSA-N 0.000 description 1
- AKZVDQZLGWCATP-UHFFFAOYSA-N CCC[S@](N)(O)#[O] Chemical compound CCC[S@](N)(O)#[O] AKZVDQZLGWCATP-UHFFFAOYSA-N 0.000 description 1
- NXJQIUFKKRJZHC-YVNMAJEFSA-N CC[C@@H](CC1)CC(C)C1C=C Chemical compound CC[C@@H](CC1)CC(C)C1C=C NXJQIUFKKRJZHC-YVNMAJEFSA-N 0.000 description 1
- IWHLPMBLJZJCJK-UHFFFAOYSA-N CNCC1CCCCC1 Chemical compound CNCC1CCCCC1 IWHLPMBLJZJCJK-UHFFFAOYSA-N 0.000 description 1
- CZZZABOKJQXEBO-UHFFFAOYSA-N Cc(cc1)cc(C)c1N Chemical compound Cc(cc1)cc(C)c1N CZZZABOKJQXEBO-UHFFFAOYSA-N 0.000 description 1
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- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
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- C07C311/43—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring having sulfur atoms of sulfonamide groups and amino groups bound to carbon atoms of six-membered rings of the same carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
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Abstract
Description
Trends in Pharmacological Sciences, Vol.15, 153(1994) Trends in Pharmacological Sciences, Vol.18, 372(1997) Peptides, Vol.18, 445(1997)
(1)式(I):
Yは−S(O)n−(nは1または2である)または−CO−であり、
R2は水素または置換基を有していてもよい低級アルキルであり、
R1およびR2は一緒になって低級アルキレンを形成してもよく、
R7は水素または置換基を有していてもよい低級アルキルであり、
Xは
置換基を有していてもよい低級アルキレン、
置換基を有していてもよい低級アルケニレン、
置換基を有していてもよい−CO−低級アルキレン、
置換基を有していてもよい−CO−低級アルケニレンまたは
但し、
[式中、R14は置換基を有していてもよいフェニルである]ではない)
であり、
−NR2−X−は
Zは置換基を有していてもよい低級アルキル、置換基を有していてもよい低級アルケニル、置換基を有していてもよいアミノ、置換基を有していてもよい低級アルコキシ、置換基を有していてもよい炭化水素環式基、置換基を有していてもよいヘテロ環式基である、
(但し、Zは3環の縮合へテロ環式基、置換基を有していてもよいチアゾリルまたは置換基を有していてもよいキナゾリニルではない)]
である化合物(但し、Xが
(2)R1が低級アルキルである、(1)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(3)Yが−S(O)2−である、(1)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(4)Zが置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である、(1)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(5)Xが
(6)Zが置換基を有していてもよいヘテロ環式基である、(5)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(7)
(8)
pおよびqは各々独立して0または1であり、pおよびqのいずれか一方は0ではない、(5)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(9)Zが置換基を有していてもよい低級アルキル、置換基を有していてもよいフェニル、置換基を有していてもよいピリジル、置換基を有していてもよいピラゾリル、置換基を有していてもよいイソオキサゾリル、置換基を有していてもよいオキサジアゾリル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニルまたは置換基を有していてもよい2環の縮合へテロ環である、(7)または(8)に記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(10)Xが
であり、p+qが1または2である、(1)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(11)p+qが1である、(10)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(12)式(I):
Yは−S(O)2−であり、
R2は水素または置換基を有していてもよい低級アルキルであり、
R7は水素または置換基を有していてもよい低級アルキルであり、
Xは
Zは置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である]
である化合物(但し、Zが3環の縮合へテロ環式基または置換基を有していてもよいピリミジニルである化合物を除く)、その製薬上許容される塩またはそれらの溶媒和物、
(13)Zが置換基を有していてもよいフェニル、置換基を有していてもよいインダニル、置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいピラゾリル、置換基を有していてもよいイソオキサゾリル、置換基を有していてもよいオキサジアゾリルまたは置換基を有していてもよい2環の縮合へテロ環である、(12)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(14)Zが置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンゾオキサゾリル、置換基を有していてもよいベンゾピリジル、置換基を有していてもよいベンゾピリダジル、置換基を有していてもよいベンゾイミダゾリル、置換基を有していてもよいチアゾロピリジル、置換基を有していてもよいイソキサゾリノニル、置換基を有していてもよいオキサゾリノニル、置換基を有していてもよいベンズオキサジノニルまたは置換基を有していてもよいベンゾキシアゼピノニルである、(12)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(15)式(I):
Yは−S(O)2−であり、
R2は水素または置換基を有していてもよい低級アルキルであり、
R7は水素または置換基を有していてもよい低級アルキルであり、
Xは
但し、
[式中、R14は置換基を有していてもよいフェニルである]ではない)であり、
Zは置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である]
である化合物(但し、Zが3環の縮合へテロ環式基、置換基を有していてもよいチアゾリルまたは置換基を有していてもよいキナゾリニルである化合物を除く)、その製薬上許容される塩またはそれらの溶媒和物、
(16)Zが置換基を有していてもよいフェニル、置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいキノリル、置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンズイミダゾリル、置換基を有していてもよいベンズオキサゾリル、置換基を有していてもよいチアゾロピリジルまたは置換基を有していてもよいオキサゾロピリジルである、(15)記載の化合物、その製薬上許容される塩またはそれらの溶媒和物、
(17)式(I):
Yは−S(O)2−であり、
R2は水素または置換基を有していてもよい低級アルキルであり、
R7は水素または置換基を有していてもよい低級アルキルであり、
Xは
Zは置換基を有していてもよいフェニル、置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいキノリル、置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンズイミダゾリル、置換基を有していてもよいベンズオキサゾリル、置換基を有していてもよいチアゾロピリジルまたは置換基を有していてもよいオキサゾロピリジルである]である化合物、その製薬上許容される塩またはそれらの溶媒和物、
(18)(1)〜(17)のいずれかに記載の化合物、その製薬上許容される塩またはそれらの溶媒和物を有効成分とする医薬組成物、
(19)(1)〜(17)のいずれかに記載の化合物、その製薬上許容される塩またはそれらの溶媒和物を有効成分とするNPY Y5受容体拮抗剤、
(20)式:
(式中、R1はエチルまたはtert-ブチルである)で示される化合物、その塩またはそれらの溶媒和物、
(21)式:
(式中、R1はエチル、イソプロピルまたはtert-ブチルである)で示される化合物、その塩またはそれらの溶媒和物、
(22)式:
(式中、Zは置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である)で示される化合物、その塩またはそれらの溶媒和物、
(23)式:
(式中、R15はNH2またはOHであり、
Zは置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいキノリル、置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンゾオキサゾリル、置換基を有していてもよいベンゾピリジル、置換基を有していてもよいベンゾピリダジル、置換基を有していてもよいベンズイミダゾリル、置換基を有していてもよいベンズオキサゾリル、置換基を有していてもよいチアゾロピリジル置換基を有していてもよいイソキサゾリノニル、置換基を有していてもよいオキサゾリノニル、置換基を有していてもよいベンズオキサジノニルまたは置換基を有していてもよいベンゾキシアゼピノニルである)で示される化合物、その塩またはそれらの溶媒和物、に関する。
R1における「低級アルキル」は好ましくは炭素数2〜10、さらに好ましくは炭素数2〜6、最も好ましくはエチル、イソプロピルまたはt−ブチルである。
(3)それぞれ下記に定義する置換基群βから選択される1以上の置換可能な基で置換されていてもよい(i)ヒドロキシ、(ii)低級アルコキシ、(iii)メルカプト、(iv)低級アルキルチオ、(v)アシル、(vi)アシルオキシ、(vii)カルボキシ、(viii)低級アルコキシカルボニル、(ix)イミノ、(x)カルバモイル、(xi)チオカルバモイル、(xii)低級アルキルカルバモイル、(xiii)低級アルキルチオカルバモイル、(xiv)アミノ、(xv)低級アルキルアミノもしくは(xvi)ヘテロ環カルボニル;または
(4)式:
Wは単結合、O、SまたはNR12であり、
R12は水素、低級アルキルまたはフェニルであり、
sは0〜4の整数)
で示される基等が挙げられる。
(6)それぞれ置換基群βから選択される1以上の置換可能な基で置換されていてもよい(i)ヒドロキシ、(ii)低級アルキル、(iii)低級アルケニル、(iv)低級アルコキシ、(v)カルボキシ、(vi)低級アルコキシカルボニル、(vii)アシル、(viii)アシルオキシ、(ix)イミノ、(x)メルカプト、(xi)低級アルキルチオ、(xii)カルバモイル、(xiii)低級アルキルカルバモイル、(xiv)シクロアルキルカルバモイル、(xv)チオカルバモイル、(xvi)低級アルキルチオカルバモイル、(xvii)低級アルキルスルフィニル、(xviii)低級アルキルスルホニル、(xix)スルファモイル、(xx)低級アルキルスルファモイルおよび(xxi)シクロアルキルスルファモイル;
(7)それぞれ置換基群β、低級アルキル、低級アルコキシ低級アルキル、保護されていてもよいヒドロキシ低級アルキル、ハロゲノ低級アルキル、低級アルキルスルホニルおよび/またはアリールスルホニルで置換されていてもよい、(i)シクロアルキル、(ii)シクロアルケニル、(iii)シクロアルキルオキシ、(iv)アミノおよび(v)アルキレンジオキシ;並びに
(8)それぞれ置換基群β、低級アルキル、ハロゲノ低級アルキルおよび/またはオキソで置換されていてもよい(i)フェニル、(ii)ナフチル、(iii)フェノキシ、(iv)フェニル低級アルコキシ、(v)フェニルチオ、(vi)フェニル低級アルキルチオ、(vii)フェニルアゾ、(viii)ヘテロ環式基、(ix)ヘテロ環オキシ、(x)ヘテロ環チオ、(xi)ヘテロ環カルボニルおよび(xii)ヘテロ環スルホニルからなる群である。
置換基を有していてもよい低級アルキル(ここで置換基とはハロゲン、シアノ、フェニル、カルボキシおよび/または低級アルコキシカルボニル);
低級アルケニル;低級アルコキシカルボニル低級アルケニル;
置換基を有していてもよい低級アルコキシ(ここで置換基とはハロゲン、ヒドロキシ、低級アルコキシ、カルボキシ、低級アルコキシカルボニル、低級アルキルアミノおよび/またはシアノ);
アシル;ヒドロキシイミノ;低級アルキルチオ;低級アルキルスルフィニル;スルファモイル;
置換基を有していてもよいアミノ(ここで置換基とは低級アルキル、保護されていてもよいヒドロキシ低級アルキル、フェニルおよび/またはアシル);
アルキレンジオキシ;シアノフェニル;ヘテロ環置換フェニル;ビフェニルイル;フェノキシ;低級アルキルで置換されていてもよいフェニルアゾ;
置換基を有していてもよいヘテロ環式基(ここで置換基とは保護されていてもよいヒドロキシ;メルカプト;ハロゲン;低級アルキル;シクロアルキル;低級アルコキシカルボニル;アミノ;低級アルコキシカルボニルアミノ;カルバモイル;オキソ;フェニル;低級アルコキシフェニル;またはヘテロ環式基)であり、さらに好ましくはハロゲン;ハロゲンで置換されていてもよい低級アルキル;ハロゲンで置換されていてもよい低級アルコキシである。
Zにおける「置換基を有していてもよいアリール」および「置換基を有していてもよいフェニル」は、置換基群α、置換基群αから選択される置換可能な1以上の基で置換されていてもよい低級アルキル等で置換されていてもよい「アリール」、「フェニル」を包含する。
−NR2−X−が
である。
(式中、Halはハロゲンであり、−G−CH2−は式(I)の−X−と同義であり、R13は低級アルキルであり、その他の記号は前記と同義である)
工程A
化合物1と目的化合物に対応する置換基R1を有するスルホニルハライド2と適当な溶媒中、0℃〜50℃で数分〜数時間反応させればnが2である化合物3が得られる。溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジエチルエーテル、ジクロロメタン、トルエン、ベンゼン、キシレン、シクロヘキサン、へキサン、クロロホルム、酢酸エチル、酢酸ブチル、ペンタン、ヘプタン、ジオキサン、アセトン、アセトニトリル、水およびそれらの混合溶媒等が使用可能である。
工程B
化合物1と置換基R1を有するスルフィニルハライド4を反応させてn=1である化合物5を得ることもできる。反応条件は上記工程Aと同様である。
工程C
工程Bで得られた化合物5を常法により酸化反応に付せば、n=2である化合物3が得られる。酸化剤としてはm−クロロ過安息香酸、過酢酸、過酸化水素、過トリフルオロ酢酸、過よう素酸ナトリウム、次亜塩素酸ナトリウム、過マンガン酸カリウム等を使用することができ、反応は0℃〜50℃で行えばよい。溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジエチルエーテル、ジクロロメタン、トルエン、ベンゼン、キシレン、シクロヘキサン、へキサン、クロロホルム、酢酸エチル、酢酸ブチル、ペンタン、ヘプタン、ジオキサン、アセトン、アセトニトリル、水、メタノール、エタノール、イソプロパノールおよびそれらの混合溶媒等を用いることができる。
工程D
工程AあるいはCで得た化合物3を適当な溶媒中、塩基で処理し、化合物6を得る。塩基としては水酸化バリウム、水酸化ナトリウム、水酸化カリウム、ヒドラジン、プロパンチオールリチウム塩等を用いることができ、溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジオキサン、アセトン、アセトニトリル、メタノール、エタノール、プロパノール、水およびそれらの混合溶媒等が使用可能である。0℃〜100℃で数分〜数十時間反応させればよい。
工程E
工程Dで得られた化合物6と目的化合物に対応する置換基ZおよびR7を有するアミノ化合物7を適当な溶媒中、0℃〜50℃で数分〜数時間反応させて化合物8を得る。溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジエチルエーテル、ジクロロメタン、トルエン、ベンゼン、キシレン、シクロヘキサン、へキサン、クロロホルム、酢酸エチル、酢酸ブチル、ペンタン、ヘプタン、ジオキサン、アセトン、アセトニトリル、水およびそれらの混合溶媒等が使用可能であり、必要であれば塩化チオニル、酸ハロゲン化物、酸無水物、活性化エステル等の活性化剤を用いてもよい。
工程F
得られた化合物8を適当な溶媒中、適当な還元剤で処理し、化合物(I−A)を得る。還元剤としては水素化ホウ素ナトリウム、水素化ホウ素リチウム、水素化リチウムアルミニウム等を用いることができ、溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジオキサン、アセトニトリル、メタノール、エタノール、プロパノール、酢酸およびそれらの混合溶媒等が使用可能である。0℃〜100℃で数分〜数十時間反応させればよい。
工程G
工程Dで得られた化合物6を適当な溶媒中、還元剤で処理し、化合物9を得る。還元剤としては水素化ホウ素ナトリウム、水素化ホウ素リチウム、水素化リチウムアルミニウム、ジボラン等を用いることができ、溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジオキサン、アセトニトリル、メタノール、エタノール、プロパノールおよびそれらの混合溶媒等が使用可能である。0℃〜100℃で数分〜数十時間反応させればよく、必要であれば酸ハロゲン化物、酸無水物、活性化エステル等の中間体を経由してもよい。
工程H
工程Gで得られた化合物9を常法により酸化反応に付せば、化合物10が得られる。酸化剤としてはm−クロロ過安息香酸、過酢酸、過酸化水素、過トリフルオロ酢酸、過よう素酸ナトリウム、次亜塩素酸ナトリウム、過マンガン酸カリウム、デス‐マーチン過よう素酸、ジメチルスルホキシド/オキサリルクロライド(Swern酸化)、ルテニウム触媒等を使用することができ、反応は−80℃〜50℃で行えばよい。溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジエチルエーテル、ジクロロメタン、トルエン、ベンゼン、キシレン、シクロヘキサン、へキサン、クロロホルム、酢酸エチル、酢酸ブチル、ペンタン、ヘプタン、ジオキサン、アセトン、アセトニトリル、水、メタノール、エタノール、イソプロパノールおよびそれらの混合溶媒等を用いることができる。
工程J
得られた化合物10と目的化合物に対応する置換基ZおよびR7を有するアミノ化合物7を常法により還元的アミノ化反応に付せば、化合物(I−A)が得られる。還元剤としては水素化ホウ素ナトリウム、トリアセトキシ水素化ホウ素ナトリウム、シアノ水素化ホウ素ナトリウム等を使用することができ、反応は0℃〜50℃で行えばよい。溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジオキサン、アセトニトリル、メタノール、エタノール、プロパノール、酢酸、塩酸およびそれらの混合溶媒等を用いることができる。
(式中、各記号は前記と同義であり、−G−CH2− は式(I)の −X− と同義である)
工程K
化合物1と目的化合物に対応する置換基R1を有するアシルハライド11と適当な溶媒中、−20℃〜50℃で数分〜数時間反応させれば化合物12が得られる。溶媒としてはテトラヒドロフラン、ジメチルホルムアミド、ジエチルエーテル、ジクロロメタン、トルエン、ベンゼン、キシレン、シクロヘキサン、へキサン、クロロホルム、酢酸エチル、酢酸ブチル、ペンタン、ヘプタン、ジオキサン、アセトン、アセトニトリル、水およびそれらの混合溶媒等が使用可能である。
工程D、工程G、工程Hおよび工程J
こうして得られた化合物12を上記工程D、工程G、工程Hおよび工程Jと同様の方法に付せば本発明に係る化合物(I-B)を得ることができる。
(式中、各記号は前記と同意義であり、−CH2−G−は式(I)の−X−と同義であり、Rはアルキル)
工程L
化合物16に、置換基R7を導入する工程である。例えば、R7X1(X1はハロゲン)を塩基存在下で反応させることにより、化合物17を得ることができる。溶媒としては、テトラヒドロフラン、ジメチルホルムアミドを使用することができる。反応は、室温で行うことができる。塩基としては、トリエチルアミン、ピリジン、ジメチルアミノピリジン等を用いることができる。なお、式(I-C)において、R7が水素である化合物は、本工程を行わない。
工程M
化合物17に置換基Zを導入する工程である。例えば、ZX1(X1はハロゲン)を塩基存在下で反応させることにより、化合物18を得ることができる。溶媒としては、メタノール、エタノール、イソプロパノール、ジメチルホルムアミド等を用いることができる。反応は、室温下または加温下で行うことができる。例えば、封管し、マイクロウェ−ブ反応装置を用いて行うこともできる。塩基としては、N,N-ジイソプロピルエチルアミン等を用いることができる。
工程N
化合物18を還元し、化合物19を得る工程である。還元剤として、水素化リチウムアルミニウムを用いることができる。溶媒としては、テトラヒロドフラン等を用いることができる。反応は、室温で行うことができる。
工程O
化合物19をアジド化して、化合物20に誘導する工程である。例えば、化合物19に、塩基としてトリエチルアミンを用い、メタンスルホニルクロライドを反応させて、化合物19をメシレートに誘導する。メシル化する際の溶媒としては、クロロホルムを用いることができる。得られた化合物に、アジ化ナトリウムを反応させ、ジメチルホルムアミド中等で、室温下または加温下で、アジド化を行い、化合物20を得ることができる。
工程P
化合物20を還元し、化合物21を得る工程である。接触還元で行うことができる。触媒としては、10%パラジウム炭素等を用いることができる。溶媒としては、エタノール等を用いることができる。
工程Q
化合物21に、式:R1−Y−X1(X1はハロゲン等、YはS、SO、SO2またはCOである)で示される化合物を反応させ、化合物22を得る工程である。式:R1−Y−X1で示される化合物として、各種のスルホニルクロライド、アシルクロライド等を用いることができる。溶媒としては、テトラヒドロフラン、ジメチルアミド等を用いることができる。反応は、室温下または加温下で行うことができる。塩基の存在下で行うのが好ましく、塩基としては、ピリジン、トリエチルアミン等を用いることができる。なお、式(I−C)において、R2が水素である化合物は、以降の工程Rを行わず、化合物22が最終目的化合物となる。また、Y=SまたはSOである式:R1−Y−X1で示される化合物を用いて反応させ、化合物22を得て、その後に酸化して、YがSO2である化合物に変換し、次の工程に用いても良い。
工程R
化合物22に、置換基R2を導入する工程である。R2X1(X1はハロゲン等)を塩基存在下で化合物22に反応させることにより、化合物(I−C)を得ることができる。塩基としては、水素化ナトリウム等を用いることができる。溶媒としては、ジメチルホルムアミド等を用いることができる。
(式中、Rは置換基を有していてもよい低級アルキルであり、R7は水素または置換基を有していてもよい低級アルキルであり、Gは1,4-シクロアルキレンであり、Zは置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である)
Rとしては、特に、低級アルキル、さらには、メチル、エチルが好ましい。特にエチルが好ましい。
R7としては、水素が好ましい。
Zとしては、置換基を有していてもよいヘテロ環式基が好ましい。
特に、以下の化合物が好ましい。
式:
(式中、R15はNH2またはOHであり、
Zは置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいキノリル、置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンゾオキサゾリル、置換基を有していてもよいベンゾピリジル、置換基を有していてもよいベンゾピリダジル、置換基を有していてもよいベンズイミダゾリル、置換基を有していてもよいベンズオキサゾリル、置換基を有していてもよいチアゾロピリジル置換基を有していてもよいイソキサゾリノニル、置換基を有していてもよいオキサゾリノニル、置換基を有していてもよいベンズオキサジノニルまたは置換基を有していてもよいベンゾキシアゼピノニルである)で示される化合物。
(式中、各記号は前記と同意義であり、−CH2−G−は式(I)の−X−と同義であり、Rはアルキル、Proはアミノ保護基である)
工程S
化合物17に、保護基を導入する工程である。保護基としては、広く、Protective Groups in Organic Synthesis(Theodra W. Greene著)等に記載の保護基を用いることができる。酸性条件下で除去することができるアミノ保護基が好ましい。ベンジルオキシカルボニル基、tert-ブチルオキシカルボニル基等があげられる。例えば、ProX1(X1はハロゲン等、Proはベンジルオキシカルボニル基、tert-ブチルオキシカルボニル等)、Pro−O−Pro(Proはベンジルオキシカルボニル基、tert-ブチルオキシカルボニル等)を塩基存在下で反応させることにより、化合物23を得ることができる。溶媒としては、テトラヒドロフラン、ジメチルホルムアミドを使用することができる。反応は、室温で行うことができる。塩基としては、トリエチルアミン、ピリジン、ジメチルアミノピリジン等を用いることができる。なお、R7が水素の化合物でも、同様に反応を行うことができる。
工程T
化合物23を還元し、化合物24を得る工程である。還元剤として、水素化リチウムアルミニウムを用いることができる。溶媒としては、テトラヒロドフラン等を用いることができる。反応は、室温で行うことができる。
工程U
化合物24をアジド化して、化合物25に誘導する工程である。例えば、化合物24に、塩基としてトリエチルアミンを用い、メタンスルホニルクロライドを反応させて、化合物24をメシレートに誘導する。メシル化する際の溶媒としては、クロロホルムを用いることができる。得られた化合物に、アジ化ナトリウムを反応させ、ジメチルホルムアミド中等で、室温下または加温下で、アジド化を行い、化合物25を得ることができる。
工程V
化合物25を還元し、化合物26を得る工程である。化合物25を、トリフェニルホスフィン及び水を用いて、還元することにより、化合物26を得る。反応は、加温下で行うことができる。溶媒としては、テトラヒドロフランを用いることができる。トリフェニルホスフィンを用いた還元法以外にも、接触還元で行うことができる。接触還元の場合は、触媒としては、10%パラジウム炭素などを用いることができる。溶媒としては、エタノールなどを用いることができる。いずれの還元法を用いるかは、使用する保護基により、適宜選択することができる。
工程W
化合物26に、式:R1−Y−X1(X1はハロゲン等、YはS、SO、SO2またはCOである)で示される化合物を反応させ、化合物27を得る工程である。式:R1−Y−X1(X1はハロゲン等)で示される化合物として、各種のスルホニルクロライド、アシルクロライド等を用いることができる。溶媒としては、テトラヒドロフラン、ジメチルアミド等を用いることができる。反応は、室温下または加温下で行うことができる。塩基の存在下で行うのが好ましく、塩基としては、ピリジン、トリエチルアミン等を用いることができる。また、Y=SまたはSOである式:R1−Y−X1で示される化合物を用いて反応させ、化合物27を得て、その後に酸化して、YがSO2である化合物に変換し、次の工程に用いても良い。
工程X
化合物27の保護基を除去する工程である。保護基の除去は、保護基によって各種の条件を選択して用いることができる。例えば、tert-ブチルオキシカルボニル基は酸ではずすことができる。ベンジルオキシカルボニル基は、接触還元等ではずすことができる。
工程Y
化合物28に置換基Zを導入する工程である。例えば、ZX1(X1はハロゲン)を塩基存在下で反応させることにより、化合物(I−D)を得ることができる。溶媒としては、メタノール、エタノール、イソプロパノール、ジメチルホルムアミド等を用いることができる。反応は、室温下または加温下で行うことができる。例えば、封管し、マイクロウェ−ブ反応装置を用いて行うこともできる。塩基としては、N,N-ジイソプロピルエチルアミン等を用いることができる。
上記の工程において、以下の中間体は有用である。
(式中、Rは置換基を有していてもよい低級アルキルであり、Proは保護基であり、R7は水素または置換基を有していてもよい低級アルキルであり、Gは1,4-シクロアルキレンであり、YはSO2またはSOであり、R1は置換基を有していてもよい低級アルキルであり、R2は水素または置換基を有していてもよい低級アルキルである)
Rとしては、特に、低級アルキル、さらには、メチル、エチルが好ましい。特にエチルが好ましい。
Proとしては、酸性条件下で除去することができるアミノ保護基が好ましい。例えば、Proとしては、式:−(C=O)-O-R(Rは置換基を有していてもよい低級アルキル、置換基を有していてもよい低級アルケニル)で示される基が好ましい。特に、tert-ブチルオキシカルボニル基が好ましい。
R7としては、水素が好ましい。
Yとしては、SO2が好ましい。
R1としては、特に、低級アルキル、さらには、イソプロピル、エチルが好ましい。特にエチルが好ましい。
R2としては、水素が好ましい。
特に、以下の化合物が好ましい。
式:
(式中、R1はエチルまたはtert-ブチルである)で示される化合物。
式:
(式中、R1はエチル、イソプロピルまたはtert-ブチルである)で示される化合物。
式:
(式中、Zは置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である)で示される化合物。
R1が置換基を有していてもよい低級アルキルである(以下、R1がR1−1であるとする)化合物、
R1がそれぞれハロゲンで置換されていてもよい炭素数1〜10のアルキルである(以下、R1がR1−2であるとする)化合物、
R1がハロゲンで置換されていてもよい炭素数1〜10のアルキルである(以下、R1がR1−3であるとする)化合物、
R1がイソプロピルまたはt−ブチルである(以下、R1がR1−4であるとする)化合物、
R2が水素または炭素数1〜3のアルキルである(以下、R2がR2−1であるとする)化合物、
R2が水素である(以下、R2がR2−2であるとする)化合物、
Xが置換基を有していてもよい低級アルキレン、置換基を有していてもよい低級アルケニレンまたは
Xが炭素数2〜6のアルキレン、炭素数3〜6のアルケニレンまたは
Xが炭素数2〜6のアルキレンまたは
Xが炭素数2〜6のアルキレンまたはそれぞれハロゲン、ヒドロキシ、低級アルキルもしくはハロゲノ低級アルキルで置換されていてもよいシクロアルキレンもしくはフェニレンである(以下、XがX−4であるとする)化合物、
Xが炭素数2〜6のアルキレンまたは炭素数5〜6のシクロアルキレンである(以下、XがX−5であるとする)化合物、
Xが炭素数3〜6のアルキレンまたは1,4−シクロヘキシレンである(以下、XがX−6であるとする)化合物、
Yが−SO−である(以下、YがY−1であるとする)化合物、
Yが−SO2−である(以下、YがY−2であるとする)化合物、
Yが−CO−である(以下、YがY−3であるとする)化合物、
Zが置換基を有していてもよい低級アルキル、置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である(以下、ZがZ−1であるとする)化合物、
Zが−(CR8R9)r−W−(CR10R11)s−V
[式中、R8、R9、R10およびR11は各々独立して水素または低級アルキルであり、2以上のR8、R9、R10および/またはR11が存在するとき、各々のR8、R9、R10およびR11は異なっていてもよく、Wは単結合、O、SまたはNR12であり、R12は水素、低級アルキルまたはフェニルであり、Vは水素、置換基を有していてもよいシクロアルキル、置換基を有していてもよいビシクロアルキル、置換基を有していてもよいアリールまたは置換基を有していてもよいヘテロ環式基であり、rは1〜4の整数であり、sは0〜4の整数である]
である(以下、ZがZ−2であるとする)化合物、
Zが−(CH2)r−W−(CH2)s−V
[式中、Wは単結合、O、SまたはNR12であり、R12は水素または低級アルキルであり、Vはそれぞれ置換基を有していてもよいアリールまたはヘテロ環式基(ここで置換基とはハロゲン、ヒドロキシ、低級アルキル、ハロゲノ低級アルキル、低級アルコキシ、低級アルケニル、アミノ、低級アルキルアミノ、アシル、カルボキシ、低級アルコキシカルボニル、フェニルまたは単環のヘテロアリール)であり、rは1〜4の整数であり、sは0〜4の整数である]
である(以下、ZがZ−3であるとする)化合物、
Zが−(CH2)r−W−(CH2)s−V
[式中、Wは単結合、O、S、NHまたはNMeであり、Vはそれぞれ置換基を有していてもよいフェニルまたはヘテロアリール(ここで置換基とはハロゲン、低級アルキル、ハロゲノ低級アルキル、低級アルコキシ、アミノまたは低級アルキルアミノ)であり、rは1〜3の整数であり、sは0または1である]
である(以下、ZがZ−4であるとする)化合物、
Zが置換基を有していてもよい炭化水素環式基
[ここで置換基とはハロゲン;ヒドロキシ;
置換基を有していてもよい低級アルキル(ここで置換基とはハロゲン、ヒドロキシ、カルボキシ、低級アルコキシカルボニル、シアノおよび/またはフェニル);
低級アルコキシカルボニルで置換されていてもよい低級アルケニル;
置換基を有していてもよい低級アルコキシ(ここで置換基とはハロゲン、ヒドロキシ、低級アルコキシ、カルボキシ、低級アルコキシカルボニル、低級アルキルアミノ、シクロアルキル、シアノおよび/またはヘテロ環式基);
シクロアルキル;シクロアルキルオキシ;アシル;低級アルキルチオ;カルバモイル;低級アルキルカルバモイル;シクロアルキルカルバモイル;ヒドロキシイミノ;
置換基を有していてもよいアミノ(ここで置換基とは低級アルキル、保護されていてもよいヒドロキシ低級アルキル、低級アルコキシ低級アルキル、アシル、低級アルキルスルホニル、アリールスルホニルおよび/またはフェニル);
ハロゲン、シアノ、フェニルおよび/またはヘテロ環式基で置換されていてもよいフェニル;
低級アルキルスルフィニル;低級アルキルスルファモイル;シクロアルキルスルファモイル;
ニトロ;シアノ;アルキレンジオキシ;低級アルキルで置換されていてもよいフェニルアゾ;フェノキシ;オキソ;
置換基を有していてもよいヘテロ環式基(ここで置換基とは保護されていてもよいヒドロキシ;メルカプト;ハロゲン;低級アルキル;シクロアルキル;低級アルコキシカルボニル;アシル;アミノ;低級アルコキシカルボニルアミノ;カルバモイル;オキソ;フェニル;低級アルコキシフェニル;ハロゲノフェニル;ヘテロ環式基および/またはオキソ);
低級アルキルで置換されていてもよいヘテロ環スルホニル;ヘテロ環オキシ;低級アルキルで置換されていてもよいヘテロ環カルボニル]
である(以下、ZがZ−5であるとする)化合物、
Zが置換基を有していてもよいフェニル
(ここで置換基とはハロゲン;ヒドロキシ;ハロゲン、ヒドロキシ、低級アルコキシカルボニル、シアノおよび/またはフェニルで置換されていてもよい低級アルキル;低級アルコキシカルボニル低級アルケニル;ハロゲン、低級アルコキシ、低級アルコキシカルボニル、シクロアルキルおよび/またはヘテロ環式基で置換されていてもよい低級アルコキシ;シクロアルキル;シクロアルキルオキシ;アシル;低級アルキルチオ;カルバモイル;低級アルキルカルバモイル;低級アルキル、ヒドロキシ低級アルキル、アシル、低級アルキルスルホニルおよび/またはフェニルで置換されていてもよいアミノ;ハロゲン、シアノ、フェニルおよび/またはヘテロ環式基で置換されていてもよいフェニル;
低級アルキルスルファモイル;シクロアルキルスルファモイル;ニトロ;アルキレンジオキシ;低級アルキルで置換されていてもよいフェニルアゾ;フェノキシ;オキソ;ヒドロキシ、ハロゲン、低級アルキル、低級アルコキシカルボニル、アミノ、カルバモイル、フェニル、ハロゲノフェニル、ヘテロ環式基および/またはオキソで置換されていてもよいヘテロ環式基;ヘテロ環オキシ;並びに/または低級アルキルで置換されていてもよいヘテロ環スルホニル)である(以下、ZがZ−6であるとする)化合物、
Zが置換基を有していてもよいフェニル
(ここで置換基とはハロゲン;ハロゲン、ヒドロキシ、低級アルコキシカルボニルおよび/またはフェニルで置換されていてもよい低級アルキル;ハロゲンおよび/またはシクロアルキルで置換されていてもよい低級アルコキシ;シクロアルキル;シクロアルキルオキシ;アシル;低級アルキルチオ;低級アルキルカルバモイル;低級アルキル、ヒドロキシ低級アルキル、アシルおよび/またはフェニルで置換されていてもよいアミノ;ピペリジルで置換されていてもよいフェニル;シクロアルキルスルファモイル;アルキレンジオキシ;フェノキシ;
低級アルキルで置換されていてもよいモルホリニルもしくはモルホリノ;ヒドロキシ、低級アルキル、低級アルコキシカルボニル、フェニル、ハロゲノフェニルおよび/またはオキソで置換されていてもよいピペリジル;ヒドロキシ、カルバモイルおよび/またはオキソで置換されていてもよいピロリジニル;フェニルまたはピリミジルで置換されていてもよいピペラジニル;ジヒドロピリジル;ピロリル;ピロリニル;ハロゲンおよび/または低級アルキルで置換されていてもよいイミダゾリル;ピラゾリル;チエニル;チアジアゾリル;フリル;オキサゾリル;イソオキサゾリル;低級アルキルおよび/またはフェニルで置換されていてもよいテトラゾリル;インドリニル;インドリル;テトラヒドロキノリル;低級アルキルで置換されていてもよいベンゾチアゾリル;オキソで置換されていてもよいテトラヒドロイソチアゾリル;オキソで置換されていてもよいベンゾピラニル;テトラヒドロピラニルオキシ;テトラヒドロフリルオキシ;低級アルキルで置換されていてもよいモルホリノスルホニル;および/または低級アルキルで置換されていてもよいピペリジルスルホニル)である(以下、ZがZ−7であるとする)化合物、
Zが置換基を有していてもよいフェニル(ここで置換基とはハロゲン、低級アルキル、ハロゲノ低級アルキル、低級アルコキシ、シクロアルキルオキシ、低級アルキルカルバモイル、フェニル、低級アルキルモルホリノおよび/またはテトラヒドロピラニルオキシ)である(以下、ZがZ−8であるとする)化合物、
Zが置換基を有していてもよいヘテロ環式基(ここで置換基とはハロゲン、ヒドロキシ、低級アルキル、ハロゲノ低級アルキル、低級アルコキシ、メルカプト、低級アルキルチオ、アシル、カルボキシ、低級アルコキシカルボニル、アミノ、低級アルキルアミノ、フェニル、ナフチル、ハロゲンで置換されていてもよいフェニルチオ、ハロゲンで置換されていてもよいフェノキシ、オキソおよび/または低級アルキルで置換されていてもよいヘテロ環式基)である(以下、ZがZ−9であるとする)化合物、
Zがそれぞれ置換基を有していてもよいチエニル、ピラゾリル、チアゾリル、チアジアゾリル、ピリジル、ピリミジニル、ピラジニル、ピリダジニル、トリアジニル、インドリル、イソインドリル、インドリニル、イソインドリニル、インダゾリル、ベンゾピラニル、ベンズオキサゾリル、ベンゾチエニル、ベンゾチアゾリル、ベンゾチアゾリニル、ベンゾチアジアゾリル、ベンズイミダゾリル、キノリル、イソキノリル、ジヒドロベンゾフリル、カルバゾリル、アクリジニル、ジベンゾフリルまたはチアゾロピリジル(ここで置換基とは低級アルキル;ハロゲノ低級アルキル;低級アルコキシ;低級アルコキシカルボニル;アシル;低級アルコキシカルボニル低級アルキル;メルカプト;それぞれハロゲンで置換されていてもよいフェニル、ナフチル、フェニルチオもしくはフェノキシ;フリル;ニトロ;オキソ;および/または低級アルキルで置換されていてもよいモルホリノ)である(以下、ZがZ−10であるとする)化合物、
Zがそれぞれ置換基を有していてもよいチエニル、チアゾリル、チアジアゾリル、ピリジル、ピラジニル、インドリル、イソインドリニル、ベンゾピラニル、キノリル、カルバゾリル、ジベンゾフリル、ベンゾピラニル、ベンゾチエニルまたはベンゾチアゾリル(ここで置換基とは低級アルキル、ハロゲノ低級アルキル、低級アルコキシ、低級アルコキシカルボニル、アシル、フェニル、ナフチル、フェニルチオ、低級アルキルモルホリノおよびオキソからなる群から選択される1以上の基)である(以下、ZがZ−11であるとする)化合物、
R1がR1−2であり、R2がR2−2であり、nが2であり、X、YおよびZの組み合わせ(X,Y,Z)が以下の組み合わせである化合物、
(X,Y,Z)=(X-3,Y-2,Z-1),(X-3,Y-2,Z-2),(X-3,Y-2,Z-3),(X-3,Y-2,Z-4),(X-3,Y-2,Z-5),(X-3,Y-2,Z-6),(X-3,Y-2,Z-7),(X-3,Y-2,Z-8),(X-3,Y-2,Z-9),(X-3,Y-2,Z-10),(X-3,Y-2,Z-11),
(X-3,Y-3,Z-1),(X-3,Y-3,Z-2),(X-3,Y-3,Z-3),(X-3,Y-3,Z-4),(X-3,Y-3,Z-5),(X-3,Y-3,Z-6),(X-3,Y-3,Z-7),(X-3,Y-3,Z-8),(X-3,Y-3,Z-9),(X-3,Y-3,Z-10),(X-3,Y-3,Z-11),
(X-4,Y-2,Z-1),(X-4,Y-2,Z-2),(X-4,Y-2,Z-3),(X-4,Y-2,Z-4),(X-4,Y-2,Z-5),(X-4,Y-2,Z-6),(X-4,Y-2,Z-7),(X-4,Y-2,Z-8),(X-4,Y-2,Z-9),(X-4,Y-2,Z-10),(X-4,Y-2,Z-11),
(X-4,Y-3,Z-1),(X-4,Y-3,Z-2),(X-4,Y-3,Z-3),(X-4,Y-3,Z-4),(X-4,Y-3,Z-5),(X-4,Y-3,Z-6),(X-4,Y-3,Z-7),(X-4,Y-3,Z-8),(X-4,Y-3,Z-9),(X-4,Y-3,Z-10),(X-4,Y-3,Z-11),
(X-5,Y-2,Z-1),(X-5,Y-2,Z-2),(X-5,Y-2,Z-3),(X-5,Y-2,Z-4),(X-5,Y-2,Z-5),(X-5,Y-2,Z-6),(X-5,Y-2,Z-7),(X-5,Y-2,Z-8),(X-5,Y-2,Z-9),(X-5,Y-2,Z-10),(X-5,Y-2,Z-11),
(X-5,Y-3,Z-1),(X-5,Y-3,Z-2),(X-5,Y-3,Z-3),(X-5,Y-3,Z-4),(X-5,Y-3,Z-5),(X-5,Y-3,Z-6),(X-5,Y-3,Z-7),(X-5,Y-3,Z-8),(X-5,Y-3,Z-9),(X-5,Y-3,Z-10)または(X-5,Y-3,Z-11)
もしくはその製薬上許容される塩、またはそれらの溶媒和物が挙げられる。
さらに、本発明化合物は、NPY Y5受容体拮抗作用のみならず、医薬としての有用性を備えており、下記いずれか、あるいは全ての優れた特徴を有している。
a)CYP酵素阻害が弱い。
b)薬物代謝酵素の誘導を起こしにくい。
c)高いバイオアベイラビリティー等良好な薬物動態を示す。
d)貧血誘発作用等の毒性が低い。
e)代謝安定性が高い。
f)高いY5受容体選択性を有している。
g)水溶性が高い。
h)脳移行性が高い。
また、本明細書中で用いる略号は以下の意味を表す。
Me:メチル
Et:エチル
i-Pr:イソプロピル
DMSO:ジメチルスルホキシド
Pd−C:パラジウム炭素
THF:テトラヒドロフラン
DMF:N,N−ジメチルホルムアミド
mCPBA:メタクロロ過安息香酸
第1工程
3−フルオロニトロベンゼン(2.00 g, 14.2 mmol)をジメチルスルホキシド15 mlに溶解させ、3,5−ジメチルピペリジン(3.21 g, 28.4 mmol)と炭酸カリウム(3.92 g, 28.4 mmol)を加え3時間150℃で攪拌した。反応液を水へあけ酢酸エチルで抽出した。有機層を水洗し無水硫酸ナトリウムで乾燥した。溶媒を減圧下留去し、残渣に酢酸エチルおよびヘキサンを加え、析出した結晶を濾取することで目的物の置換ニトロベンゼンが2.05 g、収率62%で得られた。
1H-NMR (CDCl3) δppm: 0.76 (q, 1H, J = 12.0 Hz), 0.96 (d, 6H, J = 6.3 Hz), 1.70-1.91 (m, 3H), 2.32 (t, 2H, J = 12.0 Hz), 3.62-3.72 (m, 2H), 7.17-7.25 (m, 1H), 7.34 (t, 1H, J = 8.1 Hz), 7.59 (d, 1H, J = 8.1 Hz), 7.71 (s, 1H).
第2工程
第1工程で得られた化合物(2.05 g, 8.75 mmol) をエタノール25 mlに溶解させ、10% Pd-C( 0.20g ) を加え水素添加反応を12時間行なった。Pd-Cをセライト濾過により除去し、濾液を減圧下濃縮した。残渣をシリカゲルクロマトグラフィにより精製すると目的物のアニリンが1.62 g、収率90%で得られた。
1H-NMR (CDCl3) δppm: 0.69 (q, 1H, J = 12.0 Hz), 0.92 (d, 6H, J = 6.3 Hz), 1.75-1.98 (m, 3H), 2.22 (t, 2H, J = 12.0 Hz), 3.53-3.62 (m, 2H), 6.21 (d, 1H, J = 7.5 Hz), 6.38 (s, 1H), 6.42 (d, 1H, J = 8.1 Hz), 7.04 (t, 1H, J = 8.1 Hz).
第3工程
原料カルボン酸(合成法は国際公開第01/037826号パンフレットに記載)(5.04 g, 19.1 mmol) をテトラヒドロフラン50 mlに懸濁させ、氷冷下水素化リチウムアルミニウム (0.726 g, 19.1 mmol)を加え、室温で1時間攪拌した。反応液を再び氷冷攪拌し、水( 1.5mL )を注意深く滴下した。滴下後、室温で5分間攪拌し、生じた沈殿物を濾過除去し、濾液を減圧下濃縮した。残渣に酢酸エチルおよびヘキサンを加え、析出した結晶を濾取することで目的物のアルコールが3.15 g、収率66%で得られた。
1H-NMR (DMSO-d6) δppm: 0.88 (q, 2H, J = 11.6 Hz), 1.25 (s, 9H), 1.15-1.30 (m, 3H), 1.67-1.76 (m, 2H), 1.83-1.92 (m, 2H), 2.97 (m, 1H), 3.13-3.20 (m, 2H), 4.35 (t, 1H, J = 5.2 Hz), 6.71 (d, 1H, J = 8.8 Hz).
第4工程
第3工程で得た化合物(500 mg, 2.01 mmol) をクロロホルム5 mlに溶解させ、デス‐マーチン過よう素酸(893 mg, 2.11 mmol)を加え室温で1時間攪拌した。沈殿物を濾過除去し、濾液を減圧下濃縮した。残渣をシリカゲルクロマトグラフィにより精製すると目的物のアルデヒドが385 mg、収率77%で得られた。
1H-NMR (DMSO-d6) δppm: 1.26 (s, 9H), 1.13-1.38 (m, 4H), 1.85-1.98 (m, 4H), 2.16 (m, 1H), 3.01 (m, 1H), 6.80 (d, 1H, J = 8.0 Hz), 9.54 (s, 1H).
第5工程
第2工程で得たアニリン(107 mg, 0.523 mmol) をテトラヒドロフラン3 mlに溶解させ、第4工程で得たアルデヒド(130 mg, 0.523 mmol)を加え室温で1時間攪拌した。反応液に水素化ホウ素ナトリウム(23.7mg, 0.628 mmol)を加え室温でさらに3時間攪拌した。反応液を水へあけ酢酸エチルで抽出した。有機層を水洗し無水硫酸ナトリウムで乾燥した。溶媒を減圧下留去し、残渣をシリカゲルクロマトグラフィにより精製すると目的物が99.3 mg、収率43%で得られた。
1H-NMR (DMSO-d6) δppm: 0.64 (q, 1H, J = 11.6 Hz), 0.87 (d, 6H, J = 6.0 Hz), 0.92-1.08 (m, 2H), 1.25 (s, 9H), 1.15-1.32 (m, 2H), 1.41 (m, 1H), 1.58-1.95 (m, 7H), 2.08 (t, 2H, J = 11.6 Hz), 2.75-2.82 (m, 2H), 3.00 (m, 1H), 3.48-3.55 (m, 2H), 5.31 (m, 1H), 5.94 (d, 1H, J = 8.5 Hz), 6.08-6.13 (m, 2H), 6.71 (d, 1H, J = 8.5 Hz), 6.85 (t, 1H, J = 8.5 Hz). 融点:161-162℃
第1工程
原料アミン(1.20 g, 3.64 mmol)と2‐クロロ‐5‐トリフルオロメチルピリジン(727 mg, 4.01 mmol)をイソプロパノール4 mlに懸濁させ、N, N-ジイソプロピルエチルアミン(1.87 ml, 10.9 mmol)を加え封管後、マイクロウェーブ反応装置を用いて1時間160℃の条件で反応を行なった。反応液を水へあけ酢酸エチルで抽出した。有機層を水洗し無水硫酸ナトリウムで乾燥した。溶媒を減圧下留去し、残渣をシリカゲルクロマトグラフィにより精製すると目的物のエステルが222 mg、収率20%で得られた。
第2工程
第1工程で得たエステル(207 mg, 0.685 mmol) をテトラヒドロフラン3 mlに溶解させ、氷冷下水素化リチウムアルミニウム (31.1 mg, 0.822 mmol)を加え、室温で0.5時間攪拌した。反応液を氷水へあけ酢酸エチルで抽出した後、有機層を水洗し無水硫酸ナトリウムで乾燥し、溶媒を減圧下留去することでアルコールを得た。得られたアルコールをクロロホルム3mlに溶解し、トリエチルアミン(0.28 ml, 2.04 mmol)を加え、氷冷下メタンスルホニルクロライド (0.12 ml, 1.64 mmol)を滴下し、室温で1時間攪拌した。反応液を水へあけ酢酸エチルで抽出した後、有機層を水洗し無水硫酸ナトリウムで乾燥し、溶媒を減圧下留去することでメシレートを得た。得られたメシレートをジメチルホルムアミド3mlに溶解し、アジ化ナトリウム(221 mg, 3.40 mmol)を加え、3時間100℃で攪拌した。反応液を水へあけ酢酸エチルで抽出した。有機層を水洗し無水硫酸ナトリウムで乾燥した。溶媒を減圧下留去し、残渣をシリカゲルクロマトグラフィにより精製すると目的物のアジドが178 mg、収率87%で得られた。
第3工程
第2工程で得たアジド(178 mg, 0.595 mmol) をエタノール3 mlに溶解させ、10% Pd-C( 30 mg ) を加え水素添加反応を4時間行なった。Pd-Cをセライト濾過により除去し、濾液を減圧下濃縮することでアミンを得た。
得られたアミンをテトラヒドロフラン3mlに溶解し、トリエチルアミン(0.28 ml, 0.714 mmol)を加え、氷冷下イソプロピルスルホニルクロライド (0.10 ml, 1.64 mmol)を滴下し1時間攪拌した。反応液を水へあけ酢酸エチルで抽出した後、有機層を水洗し無水硫酸ナトリウムで乾燥した。溶媒を減圧下留去し、残渣をシリカゲルクロマトグラフィにより精製すると目的物が64.8 mg、収率29%で得られた。
1H-NMR (DMSO-d6) δ: 0.92-1.06 (m, 2 H), 1.10-1.25 (m, 2H,), 1.22 (d, 6H, J = 6.4 Hz), 1.38 (m, 1H), 1.76-1.84 (m, 2H), 1.93-2.02 (m, 2H), 2.81 (t, 2H, J = 6.0 Hz), 3.08-3.19 (m, 1H), 3.69 (m, 1H), 6.53 (d, 1H, J = 8.8 Hz), 6.95 (t, 1H, J = 5.6 Hz), 7.16 (d, 1H, J = 7.6 Hz), 7.58 (d, 1H, J = 8.8 Hz), 8.26 (s, 1H) 融点:155-156℃
第1工程
原料アミン(132 g, 401 mmol)を氷冷下ジクロロメタン1000 mlに懸濁させ、トリエチルアミン(123 ml, 882 mmol)、(Boc)2O(101 ml, 440 mmol)を順に加え10分間反応させた。その後さらに室温で2時間反応させ、溶媒を留去した。クエン酸水(クエン酸一水和物50g, 水400 ml)に残渣をあけ、pH4とし、酢酸エチルで抽出した。有機層を水洗し、無水硫酸マグネシウムで乾燥し、溶媒を減圧下留去することで目的物が定量的に得られた。
1H-NMR (DMSO-d6) δppm: 1.06-1.25 (m, 2H), 1.25-1.43 (m, 2H), 1.37 (s, 9H), 1.75-1.94 (m, 4H), 2.19 (tt, 1H, J = 11.7, 3.9 Hz), 3.07-3.24 (m, 1H), 3.58 (s, 3H), 6.74 (d, 1H, J = 6.6 Hz).
第2工程
水素化リチウムアルミニウム (18.3 g, 483 mmol)をテトラヒドロフラン800 mlに懸濁させ、第1工程で得られたエステルのテトラヒドロフラン(300 ml)溶液を氷冷下攪拌しながら1時間かけてゆっくり加えた。氷冷下で10分間反応させた後、さらに室温で2.5時間反応させた。反応液を再び氷冷し、水とテトラヒドロフランの混合液(1:1, 36 ml)、2N水酸化ナトリウム水溶液(18 ml)、水(18 ml)を順に加え20分間攪拌した。その後さらに室温で1.5時間攪拌し、析出物を濾過除去し、濾液を減圧下濃縮した。残渣に酢酸エチルおよびヘキサンを加え、析出した結晶を濾取することで目的物のアルコールが79.5 g、収率87%(第1〜2工程通算)で得られた。
1H-NMR (DMSO-d6) δppm: 0.78-1.00 (m, 2H), 1.00-1.32 (m, 3H), 1.37 (s, 9H), 1.65-1.84 (m, 4H), 3.04-3.24 (m, 3H), 4.32-4.42 (m, 1H), 6.66 (d, 1H, J = 7.8 Hz).
第3工程
原料アルコール (79.5 g, 347 mmol)をテトラヒドロフラン800 mlに溶解させ、トリエチルアミン(72.5 ml, 520 mmol)、メタンスルホニルクロライド(32.2 ml, 416 mmol)を氷冷下攪拌しながら順に加え、1.5時間反応させた。反応液をクエン酸水(クエン酸一水和物30g, 水500 ml)にあけ、pH4とし、酢酸エチルで抽出後、有機層を水洗し無水硫酸マグネシウムで乾燥した。溶媒を減圧下留去する途中に析出した結晶を濾取し、ヘキサンで洗浄することでメシレートを100 g得た。得られたメシレートをジメチルホルムアミド100 mlに溶解させ、アジ化ナトリウム(63.7 g, 980 mmol)を加え、80℃で2時間反応させた。反応液を水にあけ、酢酸エチルで抽出した。有機層を水洗し、無水硫酸マグネシウムで乾燥し、溶媒を減圧下留去することで目的物のアジドが定量的(crude重量85.4 g)に得られた。
1H-NMR (DMSO-d6) δppm: 0.90-1.21 (m, 4H), 1.32-1.50 (m, 1H), 1.37 (s, 9H), 1.65-1.84 (m, 4H), 3.06-3.24 (m, 3H), 6.71 (d, 1H, J = 8.1 Hz).
第4工程
第3工程で得られたアジドを室温でテトラヒドロフラン900 mlに溶解させ、トリフェニルホスフィン(103 g, 392 mmol)、水(90 ml)を順に加え、80℃で1.5時間反応させた。溶媒770 mlを留去し、水300ml、酢酸エチル400 ml、2N塩酸150 mlを順に加え、pH2.5とし、分液抽出を行なった。有機層を2N塩酸で抽出し、水層を合わせ酢酸エチルで洗浄した後、2N水酸化ナトリウムを加えアルカリ性とし、酢酸エチル及びクロロホルムで何度も抽出を行なった。有機層を合わせ、無水硫酸マグネシウムで乾燥した。溶媒を減圧下留去し、残渣にヘキサンを加え、析出した結晶を濾取し、ヘキサンで洗浄することで目的物のアミンが41.7 g、収率53%(第3〜4工程通算)で得られた。
1H-NMR (DMSO-d6) δppm: 0.77-0.96 (m, 2H), 1.00-1.18 (m, 3H), 1.37 (s, 9H), 1.67-1.82 (m, 4H), 2.30-2.38 (m, 2H), 2.90-3.60 (m, 2H), 3.05-3.22 (m, 1H), 6.66 (d, 1H, J = 7.2 Hz).
第5工程
原料アミン(37.5 g, 164 mmol)をテトラヒドロフラン400 mlに懸濁させ、トリエチルアミン(91.7 ml, 656 mmol)、イソプロピルスルホニルクロライド(32.2 ml, 416 mmol)を順に-55〜-40℃で攪拌しながらゆっくり加え、0℃まで徐々に昇温しながら6時間反応させた。反応液を氷冷の希酸水溶液にあけ、酢酸エチルで抽出した。有機層を水洗し、無水硫酸マグネシウムで乾燥した。溶媒を減圧下留去し、残渣にイソプロピルエーテルを加え、析出した結晶を濾取し、イソプロピルエーテルで洗浄することで目的物のスルホンアミドが43.1 g、収率79%で得られた。
1H-NMR (DMSO-d6) δppm: 0.79-0.98 (m, 2H), 1.00-1.36 (m, 3H), 1.20 (d, 6H, J = 6.6 Hz), 1.37 (s, 9H), 1.70-1.84 (m, 4H), 2.72-2.80 (m, 2H), 3.04-3.22 (m, 2H), 6.68 (d, 1H, J = 8.1 Hz), 6.94 (t, 1H, J = 6.0 Hz).
第6工程
Boc保護された原料アミン(43.0 g, 128 mmol)をメタノール200 mlに懸濁させ、4N 塩酸-ジオキサン溶液(96 ml, 384 mmol) を氷冷下攪拌しながら加え、20分間反応させた後、さらに室温で3時間反応させた。反応液を再び氷冷し、イソプロピルエーテル220 mlを加え、30分間攪拌した後、析出した結晶を濾取し、イソプロピルエーテルで洗浄することで目的物のアミン塩酸塩が30.8 g、収率89%で得られた。
1H-NMR (DMSO-d6) δppm: 0.85-1.02 (m, 2H), 1.20 (d, 6H, J = 6.6 Hz), 1.20-1.40 (m, 3H), 1.75-1.84 (m, 2H), 1.90-2.00 (m, 2H), 2.73-2.82 (m, 2H), 2.83-2.97 (m, 1H), 3.08-3.20 (m, 1H), 7.01 (t, 1H, J = 5.7 Hz), 8.01 (s, 3H).
第7工程
原料アミン(190 mg, 0.700 mmol)と2-クロロ-5-トリフルオロメチルピリジン(1.27 g, 7.00 mmol)をN-メチルピロリドン4 mlに懸濁させ、N,N-ジイソプロピルエチルアミン(1.25 ml, 7.00 mmol)を加え、封管後、マイクロウェーブ反応装置を用いて20分間210℃の条件で反応を行なった。反応液を水へあけ、酢酸エチルで抽出した。有機層を水洗し、無水硫酸ナトリウムで乾燥した。溶媒を減圧下留去し、残渣をシリカゲルクロマトグラフィにより精製すると目的物化合物(Ij-1)が158 mg、収率60%で得られた。
1H-NMR (DMSO-d6) δppm: 0.80-0.98 (m, 2H), 1.02-1.18 (m, 2H), 1.17 (t, 3H, J = 7.2 Hz), 1.22-1.34 (m, 1H), 1.37 (s, 9H), 1.68-1.82 (m, 4H), 2.68-2.78 (m, 2H), 2.96 (q, 2H, J = 7.2 Hz), 3.04-3.22 (m, 1H), 6.68 (d, 1H, J = 8.1 Hz), 6.94 (t, 1H, J = 6.0 Hz).
1H-NMR (DMSO-d6) δppm: 0.79-1.00 (m, 2H), 1.01-1.20 (m, 2H), 1.22-1.34 (m, 1H), 1.25 (s, 9H), 1.37 (s, 9H), 1.70-1.86 (m, 4H), 2.81-2.90 (m, 2H), 3.04-3.22 (m, 1H), 6.68 (d, 1H, J = 8.1 Hz), 6.83 (t, 1H, J = 6.0 Hz).
R1がエチル基の場合
H-NMR (DMSO-d6) δppm: 0.84-1.02 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.20-1.40 (m, 3H), 1.74-1.82 (m, 2H), 1.90-2.00 (m, 2H), 2.72-2.80 (m, 2H), 2.83-2.96 (m, 1H), 2.97 (q, 2H, J = 7.5 Hz), 7.04 (t, 1H, J = 6.0 Hz), 8.03 (s, 3H).
R1がtert-ブチル基の場合
H-NMR (DMSO-d6) δppm: 0.84-1.04 (m, 2H), 1.16-1.38 (m, 3H), 1.26 (s, 9H), 1.74-1.84 (m, 2H), 1.92-2.02 (m, 2H), 2.82-2.98 (m, 3H), 6.90 (d, 1H, J = 6.0 Hz), 8.01 (s, 3H).
1H-NMR (DMSO-d6) δ: 0.90-1.05 (m, 2 H), 1.05-1.15 (m, 6H), 1.25 (s, 9H,), 1.15-1.32 (m, 3H), 1.41 (m, 1H), 1.75-1.98 (m, 4H), 2.11 (m, 1H), 2.58-3.38 (m, 5H), 3.58-3.76 (m, 2H), 5.17 (m, 1H), 6.25-6.92 (m, 5H) 融点:147-149℃
化合物Ia-140
1H-NMR (CDCl3) δ: 1.02-1.20 (m, 2 H), 1.17-1.32 (m, 2 H), 1.37 (d, 6H, J = 6.9 Hz), 1.46-1.70 (m, 4H), 1.86-1.95 (m, 2H), 2.08-2.18 (m, 2H), 3.01 (d, 2H, J = 6.9 Hz), 3.13 (m, 1H), 3.25 (m, 1H), 3.87 (d, 1H, J = 8.4 Hz) , 6.61(d, 2H, J = 8.7 Hz) , 7.39 (d, 2H, J = 8.7 Hz)
化合物Ia-141
1H-NMR (CDCl3) δ: 1.00-1.30 (m, 4 H), 1.37 (d, 6H, J = 6.9 Hz), 1.59 (m, 1H), 1.87-1.98 (m, 2H), 1.99-2.18 (m, 5H), 2.85 (q, 3H, J = 7.5 Hz), 2.97 (d, 2H, J = 6.9 Hz), 3.12 (m, 1H), 3.23 (m, 1H), 3.88 (d, 1H, J = 8.1 Hz) , 6.53 (d, 1H, J = 7.8 Hz) , 6.63 (brs, 1H), 7.04 (d, 1H, J = 7.8 Hz) Mass: 351[M+H]
化合物Ia-178
1H-NMR (CDCl3) δ: 1.08-1.36 (m, 4 H), 1.39 (s, 9H), 1.59 (m, 1H), 1.90-1.99 (m, 2H), 2.16-2.26 (m, 2H), 3.17-3.34 (m,3H), 3.69 (d, 1H, J = 9.3 Hz), 6.68 (d, 1H, J = 9.3 Hz), 7.77 (dd, 1H, J = 2.1 Hz and 9.3 Hz), 8.49 (brs, 1H) Mass:394[M+H]+
化合物Ib-138
1H-NMR (CDCl3) δ: 1.02-1.34 (m, 4 H), 1.37 (d, 6H, J = 6.6 Hz), 1.57 (m, 1H), 1.87-1.97 (m, 2H), 2.07-2.18 (m, 2H), 2.93 (d, 2H, J = 6.6 Hz), 3.13 (m, 1H), 3.25 (m, 1H), 3.99 (d, 1H, J = 8.4 Hz) , 6.38 (m, 1H) , 6.49 (brs, 1H), 6.97 (q, 1H, J = 9.3 Hz) Mass:347[M+H]
化合物Ii-2
1H-NMR (DMSO-d6) δ: 0.91-1.06 (m, 2H), 1.12-1.28 (m, 11H), 1.31-1.47 (m, 1H), 1.75-1.94 (m, 4H), 2.19 (t, 2H, J = 11.3 Hz), 2.79 (t, 2H, J = 6.0 Hz), 2.93-3.08 (m, 1H), 2.97 (q, 2H, J = 7.42 Hz), 3.46 (m, 2H), 3.57-3.69 (m, 2H), 5.71 (t, 1H, J = 5.2 Hz), 5.77 (d, 1H, J = 11.5 Hz), 5.88-5.96 (m, 2H), 7.01 (d, 1H, J = 7.4 Hz).
化合物Ii-3
1H-NMR (DMSO-d6) δ: 0.90-1.07 (m, 2 H), 1.15-1.21 (m, 1H), 1.27 (s, 9H), 1.40-1.49 (m, 2H), 1.82 (d, 2H, J = 11.6 Hz), 1.92 (d, 2H, J = 11.6 Hz), 2.79-2.84 (m, 2H), 2.97-3.10 (m, 1H), 3.24 (s, 3H), 3.55-3.62 (m, 2H), 3.84-3.91 (m, 2H), 5.50-5.59 (m, 1H), 6.40 (d, 1H, J = 8.0 Hz), 6.56 (s, 1H), 6.72 (d, 1H, J = 8.4 Hz), 6.97 (d, 1H, J = 8.4 Hz). 融点:166-168℃
化合物Ii-4
1H-NMR (DMSO-d6) δ: 0.87 (t, 3H, J = 7.2 Hz), 0.93-1.06 (m, 2H), 1.13-1.21 (m, 1H), 1.26 (s, 9H), 1.37-1.49 (m, 2H), 1.61-1.72 (m, 2H), 1.82 (d, 2H, J = 12.0 Hz), 1.91 (d, 2H, J = 12.0 Hz), 2.78-2.84 (m, 2H), 2.97-3.08 (m, 1H), 3.61-3.71 (m, 2H), 5.52-5.60 (m, 1H), 6.40 (d, 1H, J = 8.4 Hz), 6.56 (s, 1H), 6.73 (d, 1H, J = 8.8 Hz), 6.97 (d, 1H, J = 8.8 Hz). 融点:185-186℃
化合物Ii-5
1H-NMR (DMSO-d6) δ: 0.90-1.05 (m, 2H), 1.26 (s, 9H), 1.28-1.31 (m, 1H), 1.35-1.47 (m, 8H), 1.81 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.77-2.84 (m, 2H), 2.96-3.07 (m, 1H), 4.30-4.42 (m, 1H), 5.51-5.64 (m, 1H), 6.39 (d, 1H, J = 8.0 Hz), 6.55 (s, 1H), 6.72 (d, 1H, J = 8.8 Hz), 7.07 (d, 1H, J = 8.8 Hz). 融点:156-157℃
化合物Ii-6
1H-NMR (DMSO-d6) δ: 0.91-1.07 (m, 2H), 1.19-1.25 (m, 4H), 1.26 (s, 9H), 1.38-1.49 (m, 2H), 1.82 (d, 2H, J = 8.8 Hz), 1.91 (d, 2H, J = 8.8 Hz), 2.79-2.84 (m, 2H), 2.97-3.07 (m, 1H), 3.69-3.80 (m, 2H), 5.51-5.63 (m, 1H), 6.41 (d, 1H, J = 8.0 Hz), 6.56 (s, 1H), 6.72 (d, 1H, J = 8.8 Hz), 6.97 (d, 1H, J = 8.8 Hz). 融点:178-179℃
化合物Ii-7
1H-NMR (DMSO-d6) δ: 0.92-1.07 (m, 2H), 1.19-1.22 (m, 1H), 1.26 (s, 9H), 1.38-1.48 (m, 2H), 1.82 (d, 2H, J = 11.6 Hz), 1.91 (d, 2H, J = 11.6 Hz), 2.79-2.84 (m, 2H), 2.95-3.09 (m, 1H), 3.25 (s, 3H), 5.52-5.60 (m, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.56 (s, 1H), 6.72 (d, 1H, J = 8.4 Hz), 6.92 (d, 1H, J = 8.4 Hz). 融点:206-207℃
化合物Ii-8
1H-NMR (DMSO-d6) δ: 0.91-1.05 (m, 2H), 1.16-1.24 (m, 1H), 1.26 (s, 9H), 1.37-1.47 (m, 2H), 1.81 (d, 2H, J = 12.8 Hz), 1.90 (d, 2H, J = 12.8 Hz), 2.75-2.81 (m, 2H), 2.96-3.08 (m, 1H), 5.45-5.52 (m, 1H), 6.33 (d, 1H, J = 8.4 Hz), 6.50 (s, 1H), 6.68-6.80 (m, 2H), 11.02 (brs, 1H). 融点:213-214℃
化合物Ii-9
1H-NMR (DMSO-d6) δ: 0.91-1.08 (m, 2 H), 1.17-1.30 (m, 8H), 1.44 (brs, 1H), 1.82 (d, 2H, J = 12.4 Hz), 1.89 (d, 2H, J = 12.4 Hz), 2.78-2.82 (m, 2H), 2.97-3.15 (m, 2H), 3.23 (s, 3H), 3.55-3.62 (m, 2H), 3.83-3.90 (m, 2H), 5.52-5.59 (m, 1H), 6.40 (d, 1H, J = 8.0 Hz), 6.55 (s, 1H), 6.92 (d, 1H, J = 8.0 Hz), 6.97 (d, 1H, J = 8.4 Hz). 融点:120-121℃
化合物Ii-10
1H-NMR (DMSO-d6) δ: 0.88 (t, 3H, J = 7.2 Hz), 0.93-1.08 (m, 2H), 1.17-1.30 (m, 8H), 1.44 (brs, 1H), 1.52-1.61 (m, 2H), 1.83 (d, 2H, J = 12.0 Hz), 1.90 (d, 2H, J = 12.0 Hz), 2.78-2.84 (m, 2H), 2.98-3.15 (m, 2H), 3.62-3.71 (m, 2H), 5.52-5.60 (m, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.57 (s, 1H), 6.92 (d, 1H, J = 8.0 Hz), 6.97 (d, 1H, J = 8.4 Hz). 融点:144-145℃
化合物Ii-11
1H-NMR (DMSO-d6) δ: 0.90-1.08 (m, 2H), 1.15-1.30 (m, 8H), 1.33-1.50 (m, 7H), 1.82 (d, 2H, J = 12.0 Hz), 1.89 (d, 2H, J = 12.0 Hz), 2.78-2.86 (m, 2H), 2.96-3.14 (m, 2H), 4.30-4.45 (m, 1H), 5.50-5.61 (m, 1H), 6.40 (d, 1H, J = 7.6 Hz), 6.55 (s, 1H), 6.92 (d, 1H, J = 7.2 Hz), 7.07 (d, 1H, J = 7.6 Hz). 融点:137-138℃
化合物Ii-12
1H-NMR (DMSO-d6) δ: 0.92-1.07 (m, 2H), 1.14-1.30 (m, 11H), 1.36-1.50 (m, 1H), 1.82 (d, 2H, J = 12.0 Hz), 1.89 (d, 2H, J = 12.0 Hz), 2.78-2.85 (m, 2H), 2.97-3.15 (m, 2H), 3.69-3.79 (m, 2H), 5.52-5.60 (m, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.56 (s, 1H), 6.92 (d, 1H, J = 7.2 Hz), 6.98 (d, 1H, J = 8.4 Hz). 融点:158-159℃
化合物Ii-13
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 2H), 1.12-1.30 (m, 8H), 1.34-1.51 (m, 1H), 1.82 (d, 2H, J = 12.0 Hz), 1.88 (d, 2H, J = 12.0 Hz), 2.77-2.83 (m, 2H), 2.95-3.12 (m, 2H), 3.25 (s, 3H), 5.51-5.59 (m, 1H), 6.41 (d, 1H, J = 8.8 Hz), 6.56 (s, 1H), 6.86-6.97 (m, 2H). 融点:157-158℃
化合物Ii-14
1H-NMR (DMSO-d6) δ: 0.91-1.08 (m, 2 H), 1.12-1.30 (m, 5H), 1.38-1.50 (m, 1H), 1.82 (d, 2H, J = 12.0 Hz), 1.88 (d, 2H, J = 12.0 Hz), 2.77-2.85 (m, 2H), 2.90-3.09 (m, 3H), 3.23 (s, 3H), 3.55-3.61 (m, 2H), 3.84-3.91 (m, 2H), 5.52-5.60 (m, 1H), 6.40 (d, 1H, J = 8.4 Hz), 6.55 (s, 1H), 6.89-7.00 (m, 2H). 融点:150-151℃
化合物Ii-15
1H-NMR (DMSO-d6) δ: 0.88 (s, 3H), 0.90 (s, 3H), 0.92-1.08 (m, 2H), 1.12-1.30 (m, 5H), 1.35-1.51 (m, 1H), 1.83 (d, 2H, J = 12.4 Hz), 1.89 (d, 2H, J = 12.4 Hz), 2.00-2.16 (m, 1H), 2.77-2.84 (m, 2H), 2.90-3.10 (m, 3H), 3.42-3.55 (m, 2H), 5.50-5.65 (m, 1H), 6.40 (d, 1H, J = 8.4 Hz), 6.56 (s, 1H), 6.88-7.01 (m, 2H) 融点:132-133℃
化合物Ii-16
1H-NMR (DMSO-d6) δ: 0.87 (t, 3H, J = 6.8 Hz), 0.90-1.08 (m, 2H), 1.10-1.28 (m, 5H), 1.35-1.50 (m, 1H), 1.59-1.72 (m, 2H), 1.82 (d, 2H, J = 12.0 Hz), 1.89 (d, 2H, J = 12.0 Hz), 2.77-2.85 (m, 2H), 2.90-3.09 (m, 3H), 3.61-3.71 (m, 2H), 5.52-5.61 (m, 1H), 6.40 (d, 1H, J = 8.0 Hz), 6.56 (s, 1H), 6.97 (d, 2H, J = 8.0 Hz). 融点:136-137℃
化合物Ii-17
1H-NMR (DMSO-d6) δ: 0.92-1.06 (m, 2H), 1.12-1.28 (m, 5H), 1.33-1.50 (m, 7H), 1.81 (d, 2H, J = 12.0 Hz), 1.88 (d, 2H, J = 12.0 Hz), 2.78-2.84 (m, 2H), 2.90-3.08 (m, 3H), 4.28-4.44 (m, 1H), 5.49-5.79 (m, 1H), 6.39 (d, 1H, J = 8.0 Hz), 6.55 (s, 1H), 6.97 (d, 1H, J = 7.6 Hz), 7.07 (d, 1H, J = 8.0 Hz). 融点:124-125℃
化合物Ii-18
1H-NMR (DMSO-d6) δ: 0.90-1.07 (m, 2H), 1.12-1.29 (m, 8H), 1.36-1.51 (m, 1H), 1.82 (d, 2H, J = 12.0 Hz), 1.89 (d, 2H, J = 12.0 Hz), 2.78-2.86 (m, 2H), 2.90-3.09 (m, 3H), 3.68-3.80 (m, 2H), 5.51-5.61 (m, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.57 (s, 1H), 6.97 (d, 2H, J = 8.4 Hz). 融点:163-164℃
化合物Ii-19
1H-NMR (DMSO-d6) δ: 0.89-1.08 (m, 2H), 1.11-1.30 (m, 5H), 1.35-1.51 (m, 1H), 1.82 (d, 2H, J = 10.8 Hz), 1.89 (d, 2H, J = 10.8 Hz), 2.75-2.88 (m, 2H), 2.89-3.10 (m, 3H), 3.25 (s, 3H), 5.48-5.60 (m, 1H), 6.42 (d, 1H, J = 7.6 Hz), 6.56 (s, 1H), 6.92 (d, 1H, J = 7.6 Hz), 6.98 (d, 1H, J = 5.6 Hz). 融点:189-190℃
化合物Ii-20
1H-NMR (DMSO-d6) δ: 0.95-1.13 (m, 2H), 1.31-1.59 (m, 10H), 1.73-1.92 (m, 4H), 2.12-2.26 (m, 2H), 2.84 (d, 2H, J = 6.0 Hz), 3.07-3.30 (m, 4H), 4.30-4.46 (m, 1H), 5.64 (brs, 1H), 6.41 (d, 1H, J = 8.4 Hz), 6.57 (s, 1H), 7.08 (d, 1H, J = 8.4 Hz). 融点:165-166℃
化合物Ii-21
1H-NMR (DMSO-d6) δ: 0.86-1.25 (m, 10H), 1.40 (d, 3H, J = 6.9Hz), 1.52 (m, 1H), 1.82-1.93 (m, 4H), 2.95-3.00 (m, 5H), 3.63-3.91 (m, 2H), 4.61-4.68 (m, 1H), 6.73 (brs, 2H), 7.01 (d, 2H, J = 7.8Hz), 7.11 (d, 1H, J = 8.1Hz,).
化合物Ii-22
1H-NMR (DMSO-d6) δ: 0.98-1.10 (m, 2 H), 1.15-1.34 (m, 5H), 1.36-1.43 (m, 9H), 1.53 (m, 1H), 1.82.1-93 (m, 4H), 2.94-3.01 (m, 6H), 4.52 (m, 1H), 4.63 (m, 1H), 6.73 (brs, 2H), 7.02 (d, 1H, J = 7.5Hz), 7.21-7.25 (m, 1H).
化合物Ii-23
1H-NMR (DMSO-d6) δ: 0.86-1.04 (m, 4 H), 1.25 (s, 10H), 1.30 (s, 6H), 1.38 (s, 3H), 1.40 (s, 3H), 178-1.92 (m 4H), 2.76-2.80 (m, 2H), 3.03 (m, 1H), 4.54-4.63 (m, 1H), 5.57 (m, 1H), 6.16 (s, 1H), 6.22 (d, 1H, J = 8.4Hz), 6.76 (d, 1H, J = 8.4Hz), 6.98 (d, 1H, J = 8.4Hz).
化合物Ii-24
1H-NMR (DMSO-d6) δ: 0.98-1.11 (m, 5 H), 1.15-1.31 (m, 20H), 1.57 (m, 1H), 1.82.1-93 (m, 4H), 2.74-2.81 (m, 1H), 3.01-3.06 (m, 2H), 3.35 (m, 1H), 3.40 (m, 1H), 4.04-4.17 (m, 3H), 6.77 (d, 1H, J = 9.0Hz),
化合物Ii-25
1H-NMR (DMSO-d6) δ: 0.98-1.20 (m, 13 H), 1.30 (d, 3H, J = 3H), 1.59 (m, 1H), 1.81-1.91 (m, 4H), 2.73-2.83 (m, 1H), 2.94-3.04 (m, 4H), 3.35-3.45 (m, 2H), 4.08-4.19 (m, 3H), 6.88 (brs, 3H), 7.03 (d, 1H, J = 8.4Hz).
化合物Ii-26
1H-NMR (DMSO-d6) δ: 1.02-1.10 (m, 2H), 1.19-1.32 (m, 2H), 1.26 (s, 9H), 1.55 (m, 1H), 1.86-1.93 (m, 4H), 3.01-3.04 (m, 3H), 6.76 (d, 1H, J = 8.7 Hz), 7.03 (m, 1H), 7.37-7.43 (m, 3H), 7.76-7.80 (m, 1H), 8.20-8.23 (m, 1H), 8.34-8.40 (m, 1H), 8.78-8.79 (m, 1H)
化合物Ii-27
1H-NMR (DMSO-d6) δ: 1.03-1.10 (m, 2H), 1.20-1.30 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.53 (m, 1H), 1.88 (m, 4H), 2.99-3.15 (m, 3H), 7.33-7.35 (m, 3H), 7.71-7.75 (m, 1H), 8.16-8.18 (m, 1H), 829-8.32 (m, 1H), 8.76-8.78 (m, 1H)
化合物Ii-28
1H-NMR (DMSO-d6) δ: 1.04-1.11 (m, 2H), 1.15-1.28 (m, 2H), 1.19 (t, 3H, J =7.2 Hz), 1.59 (m, 1H), 1.87-1.91 (m, 4H), 2.93-3.08 (m, 2H), 2.97 (q, 2H, J =7.2 Hz), 3.06-3.08 (m, 2H), 7.01 (m, 1H), 7.17 (d, 1H, J =7.5Hz), 7.43 (d, 1H, J =7.5Hz), 7.50-7.57 (m, 2H), 7.80-7.84 (m, 1H), 8.25-8.27 (m, 1H), 8.39-8.44 (m, 1H), 8.80-8.82 (m, 1H)
化合物Ii-29
1H-NMR (DMSO-d6) δ: 0.99-1.10 (m, 2H), 1.15-1.28 (m, 2H), 1.19 (t, 3H, J =7.5 Hz), 1.52 (m, 1H), 1.84-1.91 (m, 4H), 2.94-3.01 (m, 5H), 6.88 (m, 1H), 7.00 (d, 1H, J =7.8 Hz), 7.26-7.28 (m, 2H), 7.38 (m, 1H), 7.76 (d, 1H, J = 3.3. Hz), 7.90 (d, 1H, J =3.3 Hz)
化合物Ii-30
1H-NMR (DMSO-d6) δ: 0.93-1.08 (m, 2 H), 1.18-1.33 (m, 2H), 1.26 (s, 9H), 1.45 (m, 1H), 1.78-1.97 (m, 4 H), 2.86-2.94 (m, 2H), 2.95-3.10 (m, 1H), 5.91 (m, 1H), 6.55 (d, 1H, J = 7.6 Hz), 6.63-6.71 (m, 2H), 6.73 (d, 1H, J = 8.0 Hz), 7.06 (s, 1H), 7.15 (t, 1H, J = 8.0 Hz), 7.60 (s, 1H), 8.11 (s, 1H), 8.31 (s, 1H)
化合物Ii-31
1H-NMR (DMSO-d6) δ: 0.93-1.08 (m, 2 H), 1.13-1.28 (m, 2H), 1.26 (s, 9H), 1.43 (m, 1H), 1.76-1.97 (m, 4 H), 2.83-3.18 (m, 3H), 5.79 (m, 1H), 6.21 (s, 2H), 6.44 (d, 1H, J = 6.8 Hz), 6.58-6.67 (m, 2H), 6.73 (d, 1H, J = 8.0 Hz), 7.10 (t, 1H, J = 8.0 Hz), 7.21 (s, 2H) 融点:205-206℃
化合物Ii-32
1H-NMR (DMSO-d6) δ: 0.90-1.05 (m, 2 H), 1.05-1.28 (m, 11H), 1.41 (m, 1H), 1.75-1.92 (m, 4 H), 2.11 (t, 2H, J = 10.0 Hz), 2.73-2.82 (m, 2H), 2.91-3.08 (m, 3H), 3.24 (d, 2H, J = 11.2 Hz), 3.62-3.72 (m, 2H), 5.07 (m, 1H), 6.47 (d, 2H, J = 7.2 Hz), 6.72 (d, 2H, J = 7.2 Hz), 6.97 (d, 1H, J = 7.6 Hz) 融点:165-166℃
化合物Ii-33
1H-NMR (DMSO-d6) δ: 0.91-1.06 (m, 2H), 1.15-1.26 (m, 8H), 1.33-1.48 (m, 1H), 1.71-1.93 (m, 4H), 2.88 (d, 2H, J = 6.5 Hz), 2.93-3.15 (m, 2H), 5.70 (brs, 2H), 6.63 (d, 2H, J = 9.1 Hz), 6.93-6.96 (m, 1H), 7.38-7.42 (m, 2H), 7.57 (d, 2H, J = 9.1 Hz), 7.88-7.93 (m, 2H)
化合物Ii-34
1H-NMR (DMSO-d6) δ: 0.98-1.02 (m, 2H), 1.16-1.18 (m, 5H), 1.42 (s, 1H), 1.75-1.91 (m, 4H), 2.88 (d, 2H, J = 6.6 Hz), 2.96 (q, 3H, J = 7.3 Hz), 6.63 (d, 2H, J = 8.9 Hz), 6.99-7.02 (m, 1H), 7.38-7.41 (m, 2H), 7.57 (d, 2H, J = 8.9 Hz), 7.89-7.92 (m, 2H).
化合物Ii-35
1H-NMR (DMSO-d6) δ: 0.90-1.52 (m, 5H), 1.19 (t, 3H, J = 7.2 Hz), 1.75-1.96 (m, 4H), 2.50-3.10 (m, 3H), 2.62 (q, 2H, J = 7.2 Hz), 5.55-5.70 (m, 1H ), 6.57 (d, 2H, J = 8.7 Hz), 6.80-7.04 (m, 4H), 7.01 (d, 1H, J = 7.8 Hz), 7.34 (d, 2H, J = 8.7 Hz)
化合物Ii-36
1H-NMR (DMSO-d6) δ: 0.90-1.50 (m, 5H), 1.19 (t, 3H, J = 7.2 Hz), 1.75-1.95 (m, 4H), 2.70-3.10 (m, 3H), 2.97 (q, 2H, J = 7.2 Hz), 3.70 (s, 3H), 5.40-5.50 (m, 1H ), 6.53 (d, 2H, J = 8.7 Hz), 6.74 (d, 2H, J = 8.7 Hz), 6.78-6.90 (m, 4H), 6.99 (d, 1H, J = 7.8 Hz)
化合物Ii-37
1H-NMR (CDCl3) δ: 1.02-1.32 (m, 4 H), 139 (s, 9H,), 1.58 (m, 1H), 1.86-1.96 (m, 2H), 2.12-2.22 (m, 2H), 3.02 (d, 2H, J = 6.6 Hz), 3.25 (m, 1H), 3.67 (d, 1H, J = 9.3 Hz) , 6.67(d, 2H, J = 8.7 Hz) , 7.41 (d, 2H, J = 8.7 Hz) Mass:393[M+H]
化合物Ii-38
1H-NMR (DMSO-d6) δ: 0.93-1.07 (m, 2H), 1.17-1.26 (m, 2H), 1.19 (t, 3H, J = 7.1 Hz), 1.43 (s, 1H), 1.77-1.85 (m, 2H), 1.85-1.94 (m, 2H), 2.82 (t, 1H, J = 5.8 Hz), 2.98 (m, 1H), 2.97 (q, 2H, J = 7.1 Hz), 5.87 (m, 1H), 6.56 (d, 2H, J = 8.6 Hz), 6.98 (d, 1H, J = 7.6 Hz), 7.02 (d, 2H, J = 8.6 Hz).
化合物Ii-39
1H-NMR (DMSO-d6) δ: 0.98-1.10 (m, 2H), 1.19-1.35 (m, 2H), 1.29 (s, 9H), 1.46 (s, 1H), 1.73-1.98 (m, 4H), 2.93 (m, 1H), 3.04 (m, 1H), 6.60-6.69 (m, 2H), 6.75 (d, 1H, J = 8.8 Hz), 6.97 (d, 1H, J = 7.6 Hz), 7.49 (d, 1H, J = 8.8 Hz), 8.05 (s, 1H).
化合物Ii-40
1H-NMR (DMSO-d6) δ: 0.96-1.09 (m, 2H), 1.16-1.29 (m, 2H), 1.19 (t, 3H, J = 7.3 Hz), 1.45 (s, 1H), 1.76-1.94 (m, 4H), 1.76 (s, 2H), 2.93 (t, 2H, J = 5.8 Hz), 2.97 (q, 2H, J = 7.3 Hz), 6.66 (s, 1H), 6.94-7.01 (m, 2H), 7.49 (d, 1H, J = 8.6 Hz), 8.04 (s, 1H).
化合物Ii-41
1H-NMR (DMSO-d6) δ: 0.91-1.05 (m, 2H), 1.17-1.33 (m, 2H), 1.26 (s, 9H), 1.35-1.48 (m, 1H), 1.76-1.86 (m, 2H), 1.86-1.95 (m, 2H), 2.76-2.82 (m, 1H), 2.96-3.08 (m, 1H), 3.71 (s, 3H), 5.21-5.30 (m, 1H), 6.57 (d, 1H, J = 8.6 Hz), 6.73 (d, 1H, J = 8.6 Hz), 7.02 (dd, 1H, J = 8.6, 2.3 Hz), 7.44 (d, 1H, J = 2.3 Hz).
化合物Ii-42
1H-NMR (DMSO-d6) δ: 0.98-1.01 (m, 2H), 1.18-1.28 (m, 2H), 1.19 (t, 3H, J = 7.1 Hz), 1.42 (s, 1H), 1.76-1.85 (m, 2H), 1.85-1.93 (m, 2H), 2.79 (t, 2H, J = 5.9 Hz), 2.97 (q, 2H, J = 7.1 Hz), 3.02 (m, 1H), 3.71 (s, 3H), 5.26 (m, 1H), 6.58 (d, 1H, J = 8.6 Hz), 6.98 (d, 2H, J = 7.8 Hz), 7.02 (d, 2H, J = 8.6 Hz), 7.44 (br s, 1H).
化合物Ii-43
1H-NMR (DMSO-d6) δ: 0.98-1.06 (m, 2H), 1.16-1.25 (m, 2H), 1.18 (t, 3H, J =7.5 Hz), 1.51 (m, 1H), 1.83-1.91 (m, 4H), 2.85 (t, 2H, J = 6.3 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.04(m, 1H), 3.56 (s, 3H), 5.46 (t, 1H, J = 6.3 Hz), 5.76 (s, 1H), 6.49 (d, 1H, J = 7.8 Hz), 7.21 (t, 1H, J = 7.5Hz), 7.32 (t, 2H, J = 7.5 Hz), 7.68 (d, 2H, J = 7.5 Hz)
化合物Ii-44
1H-NMR (DMSO-d6)δ: 0.96-1.05 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.24 (m, 2H), 1.48 (m, 1H), 1.76-1.91 (m, 4H), 2.91 (d, 2H, J = 6.6 Hz), 2.97 (q, 2H, J = 7.2 Hz), 6.35 (s, 1H), 6.99 (d, 1H, J = 7.8 Hz), 7.46-7.49 (m, 3H), 7.73-7.76 (m, 2H)
化合物Ii-45
1H-NMR (DMSO-d6) δ: 0.92-1.08 (m, 2H), 1.15-1.22 (m, 1H), 1.26 (s, 9H), 1.37-1.51 (m, 2H), 1.81 (d, 2H, J = 11.6 Hz), 1.91 (d, 2H, J = 11.6 Hz), 2.76-2.86 (m, 2H), 2.97-3.08 (m, 1H), 3.35 (s, 3H), 5.82-5.91 (m, 1H), 6.26 (d, 1H, J = 13.6 Hz), 6.39 (s, 1H), 6.73 (brs, 1H). 融点:215-216℃
化合物Ii-46
1H-NMR (CDCl3) δ: 1.02-1.32 (m, 4H), 1.24 (d, 6H, J = 6.0 Hz), 1.39 (s, 9H), 1.54 (m, 1H), 1.84-1.94 (m, 2H), 2.12-2.22 (m, 2H), 2.39 (t, 2H, J = 10.5 Hz), 2.94 (d, 2H, J = 6.9 Hz), 3.24 (m, 1H), 3.38 (d, 1H, J = 9.6 Hz), 3.61 (d, 1H, J = 9.6 Hz), 3.72-4.00 (m, 2H), 5.83-5.94 (m, 1H), 5.96-6.10 (m, 2H).
化合物Ii-47
1H-NMR (DMSO-d6) δ: 0.91-1.07 (m, 2H), 1.16-1.34 (m, 11H), 1.40 (m, 1H), 1.79 (d, 2H, J = 12.5 Hz), 1.90 (d, 2H, J = 11.9 Hz), 2.82 (t, 2H, J = 5.5 Hz), 3.01 (m, 1H), 6.12-6.18 (m, 3H), 6.30 (t, 1H, J = 5.5 Hz), 6.76 (d, 1H, J = 8.7 Hz).
化合物Ii-48
1H-NMR (CDCl3) δ: 1.00-1.28 (m, 4H), 1.39 (s, 9H), 1.56 (m, 1H), 1.91 (d, 2H, J = 12.4 Hz), 2.08-2.21 (m, 4H), 2.58 (t, 2H, J = 8.1 Hz), 2.97 (d, 2H, J = 6.0 Hz), 3.23 (m, 1H), 3.70 (d, 1H, J = 9.4 Hz), 3.80 (t, 2H, J = 7.1 Hz), 6.66 (d, 2H, J = 8.7 Hz), 7.36 (d, 2H, J = 8.7 Hz).
化合物Ii-49
1H-NMR (DMSO-d6) δ: 0.92-1.06 (m, 2H), 1.17-1.33 (m, 11H), 1.41 (m, 1H), 1.80 (d, 2H, J = 12.9 Hz), 1.90 (d, 2H, J = 11.4 Hz), 2.82 (t, 2H, J = 6.1 Hz), 3.01 (m, 1H), 6.07 (t, 1H, J = 5.3 Hz), 6.34-6.43 (m, 2H), 6.51 (dd, 1H, J1 = 8.2 Hz, J2 = 1.8 Hz), 6.75 (d, 1H, J = 8.5 Hz), 7.11 (t, 1H, 8.2 Hz).
化合物Ii-50
1H-NMR (DMSO-d6) δ: 0.92-1.08 (m, 2H), 1.14-1.31 (m, 8H), 1.43 (m, 1H), 1.76-1.94 (m, 4H), 2.82 (t, 2H, J = 6.0 Hz), 2.95-3.16 (m, 2H), 5.90 (t, 1H, J = 5.5 Hz), 6.56 (d, 2H, J = 8.7 Hz), 6.95 (d, 1H, J = 7.9 Hz), 7.03 (d, 2H, J = 8.6 Hz).
化合物Ii-51
1H-NMR (DMSO-d6) δ: 0.90-1.08 (m, 2H), 1.13-1.31 (m, 8H), 1.42 (m, 1H), 1.76-1.94 (m, 4H), 2.83 (t, 2H, J = 6.0 Hz), 2.95-3.16 (m, 2H), 6.07 (t, 1H, J = 5.4 Hz), 6.36-6.46 (m, 2H), 6.53 (dd, 1H, J1 = 8.1 Hz, J2 = 1.9 Hz), 6.95 (d, 1H, J = 7.9 Hz), 7.12 (d, 1H, J = 8.1 Hz).
化合物Ii-52
1H-NMR (DMSO-d6) δ: 0.91-1.10 (m, 2H), 1.19-1.37 (m, 11H), 1.45 (m, 1H), 1.78-1.90 (m, 4H), 2.84 (t, 2H, J = 6.0 Hz), 3.04 (m, 1H), 4.64 (q, 2H, J = 9.0 Hz), 5.73 (t, 1H, J = 5.4 Hz), 6.13-6.21 (m, 2H), 6.26 (d, 1H, J = 7.2 Hz), 6.78 (d, 1H, J = 8.4 Hz), 6.99 (t, 1H, 8.0 Hz).
化合物Ii-53
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 2H), 1.13-1.30 (m, 8H), 1.42 (m, 1H), 1.75-1.93 (m, 4H), 2.80 (t, 2H, J = 6.2 Hz), 2.93-3.16 (m, 2H), 5.66 (t, 1H, J = 5.5 Hz), 6.53 (d, 2H, J = 9.1 Hz), 6.89 (d, 2H, J = 8.8 Hz), 6.92 (t, 1H, JH-F = 75 Hz), 6.94 (d, 1H, J = 8.0 Hz).
化合物Ii-54
1H-NMR (DMSO-d6) δ: 0.88-1.05 (m, 2H), 1.14-1.32 (m, 11H), 1.41 (m, 1H), 1.75-1.94 (m, 4H), 2.77 (t, 2H, J = 6.0 Hz), 3.01 (m, 1H), 4.54 (q, 2H, J = 9.0 Hz), 5.33 (t, 1H, J = 5.8 Hz), 6.49 (d, 2H, J = 8.8 Hz), 6.75 (d, 1H, J = 8.8 Hz), 6.80 (d, 2H, J = 8.8 Hz).
化合物Ii-55
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 2H), 1.14-1.31 (m, 8H), 1.40 (m, 1H), 1.74-1.93 (m, 4H), 2.79 (t, 2H, J = 5.9 Hz), 2.94-3.15 (m, 6H), 3.69 (t, 4H, J = 4.8 Hz), 5.70-5.94 (m, 4H), 6.94 (d, 1H, J = 8.0 Hz).
化合物Ii-56
1H-NMR (DMSO-d6) δ: 0.98-1.14 (m, 2H), 1.15-1.32 (m, 5H), 1.54 (m, 1H), 1.83-1.96 (m, 4H), 2.89-3.10 (m, 5H), 6.17 (t, 1H, J = 5.2 Hz), 6.63 (d, 1H, J = 2.2 Hz), 7.02 (d, 1H, J = 7.7 Hz), 7.21 (dd, 1H, J1 = 9.1 Hz, J2 = 2.5 Hz), 7.27 (dd, 1H, J1 = 8.2 Hz, J2 = 4.4 Hz), 7.67 (d, 1H, J = 9.1 Hz), 7.97 (d, 1H, J = 8.2 Hz), 8.45 (dd, 1H, J1 = 4.3 Hz, J2 = 1.5 Hz).
化合物Ii-57
1H-NMR (DMSO-d6) δ: 0.97-1.14 (m, 2H), 1.17-1.34 (m, 8H), 1.54 (m, 1H), 1.83-1.96 (m, 4H), 2.94 (t, 2H, J = 6.0 Hz), 2.99-3.18 (m, 2H), 6.17 (t, 1H, J = 5.4 Hz), 6.63 (d, 1H, J = 2.5 Hz), 6.96 (d, 1H, J = 7.7 Hz), 7.21 (dd, 1H, J1 = 9.1 Hz, J2 = 2.5 Hz), 7.27 (dd, 1H, J1 = 8.2 Hz, J2 = 4.1 Hz), 7.67 (d, 1H, J = 9.1 Hz), 7.97 (d, 1H, J = 8.0 Hz), 8.45 (dd, 1H, J1 = 4.3 Hz, J2 = 1.5 Hz).
化合物Ii-58
1H-NMR (DMSO-d6) δ: 0.90-1.07 (m, 2H), 1.12-1.29 (m, 5H), 1.40 (m, 1H), 1.74-1.93 (m, 4H), 2.80 (t, 2H, J = 5.9 Hz), 2.92-3.07 (m, 7H), 3.69 (t, 4H, J = 4.8 Hz), 5.69-5.95 (m, 4H), 6.99 (d, 1H, J = 7.7 Hz).
化合物Ii-59
1H-NMR (DMSO-d6) δ: 0.94-1.11 (m, 2H), 1.14-1.30 (m, 5H), 1.47 (m, 1H), 1.78-1.95 (m, 4H), 2.88-3.09 (m, 5H), 3.80 (s, 3H), 6.09 (t, 1H, J = 5.6 Hz), 6.81-6.86 (m, 1H), 6.96 (dd, 1H, J1 = 8.8 Hz, J2 = 2.8 Hz), 7.01 (d, 1H, J = 7.4 Hz), 7.29 (t, 1H, J = 8.0 Hz), 7.45-7.51 (m, 2H), 7.66 (d, 1H, J = 8.5 Hz), 8.04 (d, 1H, J = 2.8 Hz).
化合物Ii-60
1H-NMR (DMSO-d6) δ: 1.03 (m, 2H), 1.19 (t, 2H, J = 7.8 Hz), 1.21 (m, 2H), 1.46 (m, 1H), 1.76-1.95 (m, 4H), 2.90 (t, 2H, J = 5.8 Hz), 2.97 (q, 2H, J = 7.3 Hz), 3.03 (m, 1H), 3.80 (s, 3H), 5.95 (m, 1H), 6.90 (m, 1H), 6.98 (d, 1H, J = 7.8 Hz), 6.98 (dd, 1H, J = 7.8, 7.8 Hz), 7.06 (d, 1H, J = 8.6 Hz), 7.26 (dd, 1H, J = 7.8, 7.8 Hz), 7.61 (d, 1H, J = 8.6 Hz), 7.69 (d, 1H, J = 7.8 Hz), 8.03 (s, 1H).
化合物Ii-61
1H-NMR (DMSO-d6) δ: 0.96-1.09 (m, 2H), 1.18-1.29 (m,2H), 1.19 (t, 3H, J = 7.6 Hz), 1.47 (m, 1H), 1.87 (m, 5H), 2.90 (t, 2H, J = 6.3 Hz), 2.97 (q, 2H, J = 7.6 Hz), 3.02 (m, 1H), 5.98 (m, 1H), 6.63 (d, 2H, J = 8.3 Hz), 6.98 (d, 1H, J = 7.3 Hz), 7.14 (m, 1H), 7.73 (s, 2H), 7.83 (d, 2H, J = 8.3 Hz), 8.52 (d, 1H, J = 4.0 Hz).
化合物Ii-62
1H-NMR (DMSO-d6) δ: 0.98-1.01 (m, 2H), 1.20 (s, 9H), 1.20-1.37 (m, 2H), 1.42 (m, 1H), 1.76-1.96 (m, 4H), 2.28-2.37 (m, 2H), 2.75-2.85 (m, 2H), 3.02 (m, 1H), 3.36 (t, 2H, J = 7.8 Hz), 3.57 (t, 2H, J = 6.3 Hz), 5.66 (m, 1H), 6.54 (d, 2H, J = 8.0 Hz), 6.73 (d, 1H, J = 8.6 Hz), 7.00 (d, 1H, J = 8.0 Hz).
化合物Ii-63
1H-NMR (DMSO-d6) δ: 0.96-1.14 (m, 2H), 1.14-1.32 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.50 (m, 1H), 1.76-1.96 (m, 4H), 2.91-3.10 (m, 3H), 2.97 (q, 2H, J = 7.2 Hz), 6.28 (m, 1H), 7.02 (d, 1H, J = 7.8 Hz), 7.32-7.46 (m, 3H), 8.20 (d, 1H, J = 6.9 Hz), 8.22 (s, 2H).
化合物Ii-64
1H-NMR (DMSO-d6) δ: 1.03-1.15 (m, 2H), 1.18-1.29 (m, 2H), 1.24 (d, 6H, J = 6.3 Hz), 1.52 (m, 1H), 1.86-1.94 (m, 2H), 2.10-2.19 (m, 2H), 2.40 (t, 2H, J = 6.0 Hz), 2.95 (d, 2H, J = 6.0 Hz), 3.23 (m, 1H), 3.40 (d, 2H, J = 11.4 Hz), 3.75-3.85 (m, 2H), 3.86 (d, 1H, J = 9.3 Hz), 6.14 (d, 1H, J = 8.5 Hz), 6.15 (s, 1H), 6.29 (d, 1H, J = 8.5 Hz), 7.06 (d, 1H, J = 8.5 Hz).
化合物Ii-65
1H-NMR (CDCl3) δ:1.08-1.16 (m, 2H), 1.14 (d, 6H, J = 6.8 Hz), 1.21-1.30 (m, 2H), 1.29 (s, 9H), 1.78 (t, 2H, J = 10.6 Hz), 1.83-1.92 (m, 2H), 2.11-2.19 (m, 2H), 2.78 (d, 2H, J = 10.6 Hz), 3.06 (s, 2H), 3.23 (m, 1H), 3.38 (s, 2H), 3.70-3.80 (m, 2H), 4.02 (d, 1H, J = 9.9 Hz), 5.37 (s, 1H), 6.30 (s, 1H).
化合物Ii-66
1H-NMR (DMSO-d6) δ: 1.01-1.12 (m, 2H), 1.20-1.34 (m, 2H), 1.27 (s, 9H), 1.54 (m, 1H), 1.82-1.99 (m, 4H), 2.91-2.98 (m, 2H), 3.06 (m ,1H), 6.17 (s, 1H), 6.63 (s, 1H), 6.78 (d, 1H, J = 9.0 Hz), 7.20 (m, 1H), 7.27 (m, 1H), 7.77 (d, 1H, J = 9.0 Hz), 7.98 (d, 1H, J = 9.0 Hz), 8.54 (s, 1H).
化合物Ii-67
1H-NMR (DMSO-d6) δ: 0.92-1.06 (m, 2H), 1.20-1.32 (m, 2H), 1.26 (s, 9H), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 1.88-1.96 (m, 2H), 2.78-2.86 (m, 2H), 3.02 (m ,1H), 5.89 (s, 1H), 6.56 (d, 1H, J = 8.4 Hz), 6.76 (d, 1H, J = 8.4 Hz), 7.02 (d, 1H, J = 8.4 Hz).
化合物Ii-68
1H-NMR (DMSO-d6) δ: 0.92-1.05 (m, 2H), 1.19 (s, 9H), 1.20-1.32 (m, 2H), 1.26 (s, 9H), 1.42 (m, 1H), 1.80-1.96 (m, 4H), 2.77 (s, 2H), 3.04 (m, 1H), 5.29 (s, 1H), 6.44 (d, 1H, J = 7.2 Hz), 6.68 (d, 1H, J = 7.2 Hz), 6.75 (d, 1H, J = 8.4 Hz).
化合物Ii-69
1H-NMR (DMSO-d6) δ: 0.95-1.10 (m, 2H), 1.20-1.32 (m, 2H), 1.26 (s, 9H), 1.47 (m, 1H), 1.80-1.88 (m, 2H), 1.88-1.95 (m, 2H), 2.88-2.95 (m, 2H), 3.02 (s, 1H), 6.07 (m, 1H), 6.77 (d, 1H, J = 8.4 Hz), 6.97 (d, 1H, J = 7.6 Hz), 7.26 (t, 1H, J = 7.6 Hz), 7.35-7.42 (m, 2H), 7.46 (d, 1H, J = 8.4 Hz), 7.91 (d, 1H, J = 7.6 Hz), 8.04 (s, 1H).
化合物Ii-70
1H-NMR (DMSO-d6) δ: 0.93-1.05 (m, 2H), 1.10-1.32 (m, 2H), 1.26 (s, 9H), 1.42 (m, 1H), 1.78-1.86 (m, 2H), 1.86-1.95 (m, 2H), 2.78-2.83 (m, 2H), 3.03 (m, 1H), 4.80 (q, 2H, J = 9.2 Hz), 5.48 (t, 1H, J = 5.6 Hz), 6.69-6.76 (m, 2H), 7.08 (dd, 1H, J = 8.8, 2.4 Hz), 7.45 (d, 1H, J = 2.4 Hz).
化合物Ii-71
1H-NMR (DMSO-d6) δ: 0.96-1.10 (m, 2H), 1.20-1.32 (m, 2H), 1.27 (s, 9H), 1.82-1.88 (m, 2H), 1.88-1.97 (m, 2H), 2.83-2.88 (m, 2H), 3.04 (m, 1H), 5.82 (s, 1H), 6.69 (m, 1H), 6.76 (d, 1H, J = 8.8 Hz), 7.12 (dd, 1H, J = 9.2, 8.8 Hz), 7.37 (m, 1H), 7.87 (d, 1H, J = 2.8 Hz), 7.99 (s, 1H).
化合物Ii-72
化合物Ii-73
化合物Ii-74
化合物Ii-75
化合物Ii-76
化合物Ii-77
化合物Ii-78
化合物Ii-79
化合物Ii-80
化合物Ii-81
化合物Ii-82
化合物Ii-83
化合物Ii-84
1H-NMR (DMSO-d6) δ: 0.91-1.08 (m, 2H), 1.14-1.30 (t, 3H, J = 7.5 Hz ), 1.41 (m, 1H), 1.73-1.94 (m, 4H), 2.34-2.46 (m, 2H), 2.85 (t, 2H, J = 6.6 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.00 (m, 1H), 3.25 (t, 2H, J = 7.5 Hz), 3.53 (t, 2H, J = 6.6 Hz), 6.27 (d, 2H, J = 11.7 Hz), 6.52 (t, 1H, J = 5.1 Hz), 7.00 (d, 1H, J = 7.2 Hz).
化合物Ii-85
化合物Ii-86
化合物Ii-87
化合物Ii-88
化合物Ii-89
化合物Ii-90
化合物Ii-91
1H-NMR (DMSO-d6) δ: 0.92-1.05 (m, 2H), 1.13 (d, 6H, J = 6.0 Hz), 1.18-1.30 (m, 2H), 1.21 (d, 6H, J = 6.4 Hz), 1.40 (m, 1H), 1.76-1.83 (m, 2H), 1.83-1.93 (m, 2H), 2.19 (dd, 1H, J = 11.2, 11.2 Hz), 2.76-2.82 (m, 2H), 3.01 (m, 1H), 3.09 (m, 1H), 3.45 (d, 2H, J = 11.2 Hz), 3.58-3.69 (m, 2H), 5.67 (m, 1H), 5.77 (d, 1H, J = 12.0 Hz), 5.90 (s, 1H), 5.91 (m, 1H), 6.91 (d, 1H, J = 7.6 Hz).
化合物Ii-92
1H-NMR (DMSO-d6) δ: 0.90-1.07 (m, 2H), 1.14-1.30 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.32-1.46 (m, 1H), 1.75-1.92 (m, 4H), 2.78-2.83 (m, 2H), 2.95-3.18 (m, 6H), 3.66-3.72 (m, 4H), 5.75 (brs, 1H), 6.00 (s, 1H), 6.04 (s, 1H), 6.11 (s, 1H), 6.95 (d, 1H, J = 9.0 Hz).
化合物Ii-93
1H-NMR (DMSO-d6) δ: 0.90-1.08 (m, 2H), 1.13-1.27 (m, 5H), 1.42 (m, 1H), 1.74-1.93 (m, 4H), 2.30-2.40 (m, 2H), 2.81 (d, 2H, J = 6.6 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.00 (m, 1H), 3.49 (t, 2H, J = 7.5 Hz), 3.66 (t, 2H, J = 6.6 Hz), 5.00-5.50 (brs, 2H), 6.07-6.15 (m, 2H), 6.25(s, 1H), 7.00 (d, 1H, J = 6.6Hz).
化合物Ii-94
1H-NMR (DMSO-d6) δ: 0.92-1.07 (m, 2H), 1.15-1.32 (m, 5H), 1.21 (d, 6H, J = 6.9 Hz), 1.42 (m, 1H), 1.74-1.93 (m, 4H), 2.30-2.42 (m, 2H), 2.81 (d, 2H, J = 6.6 Hz), 2.92-3.18 (m, 2H), 3.49 (t, 2H, J = 7.5 Hz), 3.66 (t, 2H, J = 6.6 Hz), 4.70-5.30 (brs, 2H), 6.05-6.16 (m, 2H), 6.25 (s, 1H), 6.95 (d, 1H, J = 8.1Hz).
化合物Ii-95
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 2H), 1.16-1.31 (d, 6H, J = 6.9 Hz), 1.40 (m, 1H), 1.73-1.94 (m, 4H), 2.34-2.46 (m, 2H), 2.84 (t, 2H, J = 6.0 Hz), 2.94-3.16 (m, 2H), 3.28 (t, 2H, J = 7.5 Hz), 3.53 (t, 2H, J = 6.6 Hz), 6.27 (d, 2H, J = 11.7 Hz), 6.52 (t, 1H, J = 5.4 Hz), 6.94 (d, 1H, J = 7.8 Hz).
化合物Ii-96
1H-NMR (DMSO-d6) δ: 0.91-1.04 (m, 2H), 1.20-1.32 (m, 2H), 1.26 (s, 9H), 1.40 (m, 1H), 1.76-1.95 (m, 4H), 2.77-2.83 (m, 2H), 2.99-3.04 (m, 5H), 3.67-3.72 (m, 4H), 5.71 (m, 1H), 5.79 (d, 1H, J = 11.7 Hz), 5.89 (s, 1H), 5.90 (m, 1H), 6.72 (d, 1H, J = 8.4 Hz).
化合物Ii-97
1H-NMR (DMSO-d6) δ: 0.92-1.03 (m, 2H), 1.20-1.32 (m, 2H), 1.26 (s, 9H), 1.41 (m, 1H), 1.77-1.93 (m, 4H), 2.78-2.83 (m, 2H), 2.97-3.05 (m, 5H), 3.68-3.72 (m, 4H), 5.36 (m, 1H), 6.04 (d, 1H, J = 8.0 Hz), 6.10 (s, 1H), 6.11 (d, 1H, J = 8.0 Hz), 6.72 (d, 1H, J = 8.0 Hz), 6.89 (dd, 1H, J = 8.0, 8.0 Hz).
化合物Ii-98
1H-NMR (DMSO-d6) δ: 0.92-1.04 (m, 2H), 1.17-1.29 (m, 2H), 1.21 (d, 6H, J = 6.4 Hz), 1.41 (m, 1H), 1.75-1.92 (m, 4H), 2.77-2.83 (m, 2H), 2.95-3.05 (m, 5H), 3.09 (m, 1H), 3.67-3.72 (m, 4H), 5.36 (m, 1H), 6.04 (d, 1H, J = 8.0 Hz), 6.10 (s, 1H), 6.11 (d, 1H, J = 8.0 Hz), 6.89 (dd, 1H, J = 8.0, 8.0 Hz), 6.92 (d, 1H, J = 8.0 Hz).
化合物Ii-99
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 2H), 1.15-1.31 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.39 (m, 1H), 1.47-1.62 (m, 6H), 1.74-1.94 (m, 4H), 2.78 (t, 2H, J = 6.0 Hz), 2.93-3.16 (m, 6H), 5.64-5.76 (m, 2H), 5.83-5.92 (m, 2H), 6.94 (d, 1H, J = 7.8 Hz).
化合物Ii-100
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 2H), 1.15-1.30 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.40 (m, 1H), 1.74-1.96 (m, 8H), 2.79 (t, 2H, J = 6.0 Hz), 2.93-3.18 (m, 6H), 5.48-5.67 (m, 4H), 6.94 (d, 1H, J = 8.1 Hz).
化合物Ii-101
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 2H), 1.13-1.29 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.39 (m, 1H), 1.47-1.62 (m, 6H), 1.75-1.94 (m, 4H), 2.79 (t, 2H, J = 6.0 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.03-3.10 (m, 4H), 5.64-5.75 (m, 2H), 5.83-5.91 (m, 2H), 7.00 (d, 1H, J = 7.8 Hz).
化合物Ii-102
1H-NMR (DMSO-d6) δ: 0.90-1.07 (m, 2H), 1.13-1.29 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.41 (m, 1H), 1.74-1.96 (m, 8H), 2.79 (t, 2H, J = 6.0 Hz), 2.97 (q, 2H, J = 7.5 Hz), 3.00 (m, 1H), 3.09-3.19 (m, 4H), 5.46-5.66 (m, 4H), 6.99 (d, 1H, J = 7.2 Hz).
化合物Ii-103
1H-NMR (DMSO-d6) δ: 0.91-1.03 (m, 2H), 1.16-1.29 (m, 2H), 1.21 (d, 6H, J = 6.8 Hz), 1.40 (m, 1H), 1.75-1.92 (m, 4H), 2.20 (s, 3H), 2.35-2.43 (m, 4H), 2.75-2.82 (m, 2H), 2.88-3.13 (m, 6H), 5.67 (m, 1H), 5.76 (d, 1H, J = 11.2 Hz), 5.82-5.92 (m, 2H), 6.91 (d, 1H, J = 8.0 Hz).
化合物Ii-104
1H-NMR (DMSO-d6) δ: 0.92-1.02 (m, 2H), 1.19-1.32 (m, 2H), 1.26 (s, 9H), 1.39 (m, 1H), 1.75-1.95 (m, 4H), 2.19 (s, 3H), 2.38-2.42 (m, 4H), 2.77-2.83 (m, 5H), 2.98-3.09 (m, 5H), 5.67 (m, 1H), 5.76 (d, 1H, J = 11.2 Hz), 5.88 (m, 1H), 5.88 (s, 1H), 6.72 (d, 1H, J = 8.8 Hz).
化合物Ii-105
1H-NMR (DMSO-d6) δ: 0.95-1.09 (m, 2H), 1.18-1.31 (m, 2H), 1.22 (d, 6H, J = 6.8 Hz), 1.44 (m, 1H), 1.78-1.93 (m, 4H), 2.87-2.92 (m, 2H), 3.03 (m, 1H), 3.10 (m, 1H), 6.13 (m, 1H), 6.21 (m, 1H), 6.22 (s, 2H), 6.51 (s, 1H), 6.52 (d, 1H, J = 8.0 Hz), 6.92 (d, 1H, J = 8.0 Hz), 7.26 (s, 2H).
化合物Ii-106
1H-NMR (DMSO-d6) δ: 0.97-1.08 (m, 2H), 1.17-1.29 (m, 5H), 1.40-1.68 (m, 3H), 1.80-1.92 (m, 2H), 2.90 (t, 2H, J = 6.0 Hz), 2.94-3.06 (m, 3H), 6.12-6.22 (m, 4H), 6.50-6.54 (m, 2H), 6.94-7.00 (m, 1H), 7.26-7.27 (m, 2H).
化合物Ii-107
1H-NMR (DMSO-d6) δ: 0.91-1.03 (m, 2H), 1.16-1.29 (m, 2H), 1.21 (d, 6H, J = 6.4 Hz), 1.40 (m, 1H), 1.74-1.92 (m, 4H), 2.75-2.81 (m, 2H), 2.84 (s, 3H), 3.00 (m, 1H), 3.09 (m, 1H), 3.25 (s, 3H), 3.35-3.47 (m, 4H), 5.59-5.67 (m, 4H), 6.91 (d, 1H, J = 8.0 Hz).
化合物Ii-108
1H-NMR (DMSO-d6) δ: 0.92-1.03 (m, 2H), 1.18-1.32 (m, 2H), 1.26 (s, 9H), 1.40 (m, 1H), 1.75-1.94 (m, 4H), 2.75-2.81 (m, 2H), 2.83 (s, 3H), 3.01 (m, 1H), 3.25 (s, 3H), 3.34-3.47 (m, 4H), 5.58-5.70 (m, 4H), 6.72 (d, 1H, J = 8.4 Hz).
化合物Ii-109
1H-NMR (DMSO-d6) δ: 0.90-1.51 (m, 10H), 1.21 (d, 6H, J = 6.9 Hz), 1.56-1.67 (m, 3H), 1.71-1.93 (m, 6H), 2.64 (s, 3H), 2.78 (t, 2H, J = 6.0 Hz), 2.93-3.17 (m, 2H), 3.44 (m, 1H), 5.56-5.77 (m, 4H), 6.94 (d, 1H, J = 7.8 Hz).
化合物Ii-110
1H-NMR (DMSO-d6) δ: 0.83-1.01 (m, 2H), 1.00-1.40 (m, 3H), 1.21 (d, 6H, J = 6.9 Hz), 1.68-1.91 (m, 4H), 2.73 (t, 2H, J = 6.0 Hz), 2.90-3.15 (m, 2H), 2.95 (s, 3H), 4,48 (s, 2H), 5.60-5.72 (m, 4H), 6.94 (d, 1H, J = 7.8 Hz), 7.15-7.35 (m, 5H).
化合物Ii-111
1H-NMR (DMSO-d6) δ: 0.97-1.14 (m, 2H), 1.14-1.33 (m, 5H), 1.45-1.61 (m, 1H), 1.81-1.96 (m, 4H), 2.90-3.10 (m, 5H), 6.34 (t, 1H, J = 5.2 Hz), 6.51 (d, 1H, J = 2.2 Hz), 6.99-7.07 (m, 2H), 7.36 (dd, 1H, J = 8.2, 4.1 Hz), 8.02 (d, 1H, J = 8.5 Hz), 8.48 (dd, 1H, J = 4.1, 1.4 Hz).
化合物Ii-112
1H-NMR (DMSO-d6) δ: 0.97-1.13 (m, 2H), 1.17-1.34 (m, 8H), 1.45-1.59 (m, 1H), 1.81-1.99 (m, 4H), 2.94 (t, 2H, J = 5.9 Hz), 2.99-3.21 (m, 2H), 6.33 (t, 1H, J = 5.4 Hz), 6.51 (d, 1H, J = 2.2 Hz), 6.96 (d, 1H, J = 7.7 Hz), 7.02 (dd, 1H, J = 13.5, 2.2 Hz), 7.36 (dd, 1H, J = 8.2, 4.1 Hz), 8.02 (d, 1H, J = 8.5 Hz), 8.48 (dd, 1H, J = 4.1, 1.4 Hz).
化合物Ii-113
1H-NMR (DMSO-d6) δ: 0.93-1.13 (m, 2H), 1.15-1.34 (m, 8H), 1.39-1.57 (m, 1H), 1.79-1.95 (m, 4H), 2.87 (t, 2H, J = 6.2 Hz), 2.94-3.16 (m, 2H), 3.54 (s, 3H), 5.66 (t, 1H, J = 5.5 Hz), 6.49 (d, 1H, J = 9.6 Hz), 6.73 (d, 1H, J = 2.8 Hz), 6.91-7.02 (m, 2H), 7.29 (d, 1H, J = 9.3 Hz), 7.72 (d, 1H, J = 9.3 Hz).
化合物Ii-114
1H-NMR (DMSO-d6) δ: 0.93-1.10 (m, 2H), 1.14-1.33 (m, 8H), 1.41-1.56 (m, 1H), 1.79-1.94 (m, 4H), 2.89 (t, 2H, J = 6.0 Hz), 2.95-3.16 (m, 2H), 6.00 (t, 1H, J = 5.4 Hz), 6.84 (dd, 1H, J = 8.8, 2.2 Hz), 6.95 (d, 1H, J = 8.0 Hz), 7.07 (d, 1H, J = 2.2 Hz), 7.72 (d, 1H, J = 8.8 Hz), 8.86 (s, 1H).
化合物Ii-115
1H-NMR (DMSO-d6) δ: 0.94-1.06 (m, 4H), 1.26 (s, 9H), 1.40-1.51 (m, 1H), 1.84 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.85-2.90 (m, 2H), 2.97-3.06 (m, 1H), 5.93-5.99 (m, 1H), 6.63-6.79 (m, 3H), 7.40 (d, 1H, J = 8.8 Hz), 8.32 (s, 1H).
化合物Ii-116
1H-NMR (DMSO-d6) δ: 0.95-1.07 (m, 4H), 1.26 (s, 9H), 1.39-1.47 (m, 1H), 1.80 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.87-2.93 (m, 2H), 2.98-3.06 (m, 1H), 3.37 (s, 3H), 6.27 (s, 1H), 6.55 (d, 1H, J = 8.8 Hz), 6.73 (d, 1H, J = 8.8 Hz), 6.80 (t, 1H, J = 5.2 Hz), 7.32 (d, 1H, J = 8.8 Hz).
化合物Ii-117
1H-NMR (DMSO-d6) δ: 0.94-1.08 (m, 4H), 1.20 (s, 3H), 1.22 (s, 3H), 1.39-1.51 (m, 1H), 1.80 (d, 2H, J = 12.4 Hz), 1.88 (d, 2H, J = 12.4 Hz), 2.87-2.94 (m, 2H), 2.97-3.07 (m, 1H), 3.08-3.14 (m, 1H), 3.37 (s, 3H), 6.27 (s, 1H), 6.55 (d, 1H, J = 8.4 Hz), 6.82 (t, 1H, J = 5.6 Hz), 6.94 (d, 1H, J = 8.0 Hz), 7.32 (d, 1H, J = 8.4 Hz).
化合物Ii-118
1H-NMR (DMSO-d6) δ: 0.92-1.06 (m, 4H), 1.26 (s, 9H), 1.38-1.50 (m, 1H), 1.83 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.80-2.86 (m, 2H), 2.96-3.06 (m, 1H), 3.26 (s, 3H), 5.58-5.65 (m, 1H), 6.27 (d, 1H, J = 8.4 Hz), 6.38 (s, 1H), 6.75 (d, 1H, J = 8.4 Hz), 6.99 (d, 1H, J = 8.4 Hz).
化合物Ii-119
1H-NMR (DMSO-d6) δ: 0.94-1.06 (m, 4H), 1.26 (s, 9H), 1.39-1.50 (m, 1H), 1.84 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.81-2.89 (m, 2H), 2.96-3.07 (m, 1H), 3.51 (s, 3H), 5.79-5.84 (m, 1H), 6.60 (s, 1H), 6.75 (d, 1H, J = 8.8 Hz), 7.03 (d, 1H, J = 8.8 Hz), 7.19 (d, 1H, J = 8.8 Hz).
化合物Ii-120
1H-NMR (DMSO-d6) δ: 0.93-1.10 (m, 4H), 1.26 (s, 9H), 1.37-1.40 (m, 1H), 1.42 (s, 3H), 1.44 (s, 3H), 1.83 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.79-2.96 (m, 2H), 2.97-3.07 (m, 1H), 4.33-4.46 (m, 1H), 5.50-5.59 (m, 1H), 6.25 (d, 1H, J = 8.8 Hz), 6.57 (s, 1H), 6.75 (d, 1H, J = 8.4 Hz), 7.00 (d, 1H, J = 8.4 Hz).
化合物Ii-121
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 4H), 1.26 (s, 9H), 1.36-1.49 (m, 1H), 1.82 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.80-2.87 (m, 2H), 2.95-3.97 (m, 1H), 3.27 (s, 3H), 5.85-5.92 (m, 1H), 6.33 (s, 1H), 6.36 (s, 1H), 6.75 (d, 1H, J = 8.8 Hz).
化合物Ii-122
1H-NMR (DMSO-d6) δ: 0.92-1.08 (m, 4H), 1.26 (s, 9H), 1.38-1.41 (m, 1H), 1.42 (s, 3H), 1.43 (s, 3H), 1.82 (d, 2H, J = 11.8 Hz), 1.90 (d, 2H, J = 11.8 Hz), 2.83-2.88 (m, 2H), 2.98-3.06 (m, 1H), 4.33-4.47 (m, 1H), 6.35 (s, 1H), 6.54 (s, 1H), 6.76 (d, 1H, J = 8.4 Hz), 8.32 (s, 1H).
化合物Ii-123
1H-NMR (DMSO-d6) δ: 0.93-1.06 (m, 4H), 1.22 (s, 3H), 1.24 (s, 3H), 1.26 (s, 9H), 1.39-1.50 (m, 1H), 1.81 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.87-2.93 (m, 2H), 2.96-3.07 (m, 1H), 4.39-4.47 (m, 1H), 6.30 (s, 1H), 6.54 (d, 1H, J = 8.8 Hz), 6.77 (d, 1H, J = 8.8 Hz), 6.86 (t, 1H, J = 5.2 Hz), 7.32 (d, 1H, J = 8.4 Hz).
化合物Ii-124
1H-NMR (DMSO-d6) δ: 0.90-1.05 (m, 4H), 1.26 (s, 9H), 1.36-1.51 (m, 1H), 1.79 (d, 2H, J = 12.4 Hz), 1.90 (d, 2H, J = 12.4 Hz), 2.80-2.86 (m, 2H), 3.01 (s, 3H), 3.02-3.05 (m, 1H), 3.49 (t, 2H, J = 4.8 Hz), 4.26 (t, 2H, J = 4.8 Hz), 6.02 (s, 1H), 6.20 (t, 1H, J = 5.6 Hz), 6.31 (d, 1H, J = 8.8 Hz), 6.74 (d, 1H, J = 8.8 Hz), 7.43 (d, 1H, J = 8.4 Hz).
化合物Ii-125
1H-NMR (DMSO-d6) δ: 0.92-1.02 (m, 4H), 1.08 (t, 3H, J = 7.2 Hz), 1.25 (s, 9H), 1.35-1.42 (m, 1H), 1.79 (d, 2H, J = 12.0 Hz), 1.90 (d, 2H, J = 12.0 Hz), 2.80-2.86 (m, 2H), 2.96-3.05 (m, 1H), 3.42-3.51 (m, 4H), 4.20-4.26 (m, 2H), 6.03 (s, 1H), 6.20 (s, 1H), 6.31 (d, 1H, J = 8.8 Hz), 6.75 (d, 1H, J = 8.8 Hz), 7.42 (d, 1H, J = 8.8 Hz).
化合物Ii-126
1H-NMR (DMSO-d6) δ: 0.92-1.02 (m, 4H), 1.09 (s, 3H), 1.11 (s, 3H), 1.25 (s, 9H), 1.43−1.55 (m, 1H), 1.80 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.0 Hz), 2.84 (m, 2H), 2.97-3.08 (m, 1H), 3.37 (t, 2H, J = 5.2 Hz), 4.18 (t, 2H, J = 5.2 Hz), 4.71-4.80 (m, 1H), 6.05 (s, 1H), 6.19 (t, 1H, J = 5.2 Hz), 6.32 (d, 1H, J = 8.8 Hz), 6.74 (d, 1H, J = 8.4 Hz), 7.18 (d, 1H, J = 8.4 Hz).
化合物Ii-127
1H-NMR (DMSO-d6) δ: 0.94-1.12 (m, 2H), 1.14-1.39 (m, 5H), 1.34-1.56 (m, 1H), 1.70-1.97 (m, 4H), 2.87-3.10 (m, 5H), 6.17 (t, 1H, J = 5.2 Hz), 6.94-7.06 (m, 2H), 7.35-7.47 (m, 4H), 7.75-7.80 (m, 1H), 8.07 (d, 1H, J = 3.0 Hz).
化合物Ii-128
1H-NMR (DMSO-d6) δ: 0.96-1.12 (m, 2H), 1.14-1.31 (m, 5H), 1.31-1.55 (m, 1H), 1.70-1.96 (m, 4H), 2.89-3.09 (m, 5H), 6.24 (t, 1H, J = 5.4 Hz), 6.94-7.05 (m, 2H), 7.24 (d, 1H, J = 6.9 Hz), 7.52 (t, 1H, J = 8.0 Hz), 7.75 (d, 1H, J = 8.8 Hz), 7.88-7.97 (m, 2H), 8.07 (d, 1H, J = 2.5 Hz).
化合物Ii-129
1H-NMR (DMSO-d6) δ: 0.98-1.12 (m, 2H), 1.18-1.30 (m, 2H), 1.19 (t, 3H, J = 6.8 Hz), 1.48 (m, 1H), 1.79-1.95 (m, 4H), 2.92-3.09 (m, 3H), 2.97 (q, 2H, J = 6.8 Hz), 6.27 (m, 1H), 7.01 (d, 1H, J = 8.0 Hz), 7.39-7.47 (m, 2H), 7.56 (m, 1H), 8.18-8.25 (m, 2H), 8.23 (s, 2H).
化合物Ii-130
1H-NMR (DMSO-d6) δ: 0.96-1.12 (m, 2H), 1.15-1.30 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.45-1.64 (m, 1H), 1.78-1.96 (m, 4H), 2.97 (q, 2H, J = 7.2 Hz), 2.95-3.15 (m, 1H), 3.22-3.28 (m, 2H), 6.89 (d, 1H, J = 9.0 Hz), 6.94-7.02 (m, 2H), 7.38 (t, 1H, J = 6.0 Hz), 7.46 (t, 2H, J = 7.5 Hz), 7.78 (d, 1H, J = 9.0 Hz), 7.96 (d, 2H, J = 9.0 Hz).
化合物Ii-131
1H-NMR (DMSO-d6) δ: 0.96-1.12 (m, 2H), 1.15-1.30 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.48-1.62 (m, 1H), 1.78-1.96 (m, 4H), 2.98 (q, 2H, J = 7.2 Hz), 2.94-3.10 (m, 1H), 3.22-3.28 (m, 2H), 6.89 (d, 1H, J = 9.0 Hz), 7.02 (d, 1H, J = 9.0 Hz), 7.10 (t, 1H, J = 5.4 Hz), 7.22 (td, 1H, J = 9.0, 3.0 Hz), 7.47-7.56 (m, 1H), 7.77-7.88 (m, 3H).
化合物Ii-132
1H-NMR (DMSO-d6) δ: 0.96-1.13 (m, 2H), 1.15-1.32 (m, 2H), 1.19 (t, 3H, J = 7.5 Hz), 1.48-1.65 (m, 1H), 1.78-1.96 (m, 4H), 2.98 (q, 2H, J = 7.2 Hz), 2.94-3.12 (m, 1H), 3.22-3.28 (m, 2H), 6.89 (d, 1H, J = 9.0 Hz), 7.01 (d, 1H, J = 6.0 Hz), 7.09 (t, 1H, J = 5.4 Hz), 7.27-7.35 (m, 2H), 7.42-7.50 (m, 1H), 7.57 (dd, 1H, J = 9.0, 3.0 Hz), 7.86 (td, 1H, J = 7.5, 3.0 Hz).
化合物Ii-133
1H-NMR (DMSO-d6) δ: 0.92-1.08 (m, 2H), 1.15-1.30 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.42-1.58 (m, 1H), 1.72-1.94 (m, 4H), 2.95-3.20 (m, 4H), 4.89-4.98 (m, 2H), 6.65 (brs, 1H), 6.92 (d, 1H, J = 9.0 Hz), 6.91-6.98 (m, 1H), 7.03 (d, 1H, J = 9.0 Hz).
化合物Ii-134
1H-NMR (DMSO-d6) δ: 0.90-1.08 (m, 2H), 1.15-1.30 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.42-1.58 (m, 1H), 1.72-1.94 (m, 4H), 2.92-3.20 (m, 4H), 6.74 (t, 1H, J = 6.0 Hz), 6.94 (t, 1H, J = 6.0 Hz), 6.97 (s, 1H), 7.08-7.24 (m, 5H).
化合物Ii-135
1H-NMR (DMSO-d6) δ: 0.95-1.10 (m, 2H), 1.12-1.30 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.48-1.60 (m, 1H), 1.76-1.94 (m, 4H), 2.92-3.10 (m, 1H), 2.97 (q, 2H, J = 7.2 Hz), 3.18-3.30 (m, 2H), 6.89 (d, 1H, J = 9.6 Hz), 7.02 (brs, 1H), 7.11 (t, 1H, J = 5.4 Hz), 7.42-7.56 (m, 2H), 7.85 (d, 1H, J = 9.6 Hz), 7.93 (d, 1H, J = 7.5 Hz), 8.03 (s, 1H).
化合物Ii-136
1H-NMR (DMSO-d6) δ: 0.98-1.12 (m, 2H), 1.13-1.30 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.48-1.62 (m, 1H), 1.78-1.96 (m, 4H), 2.92-3.12 (m, 1H), 2.97 (q, 2H, J = 7.2 Hz), 3.22-3.32 (m, 2H), 6.89 (d, 1H, J = 9.0 Hz), 7.01 (d, 1H, J = 7.5 Hz), 7.20 (t, 1H, J = 6.0 Hz), 7.62 (s, 1H), 7.91 (d, 1H, J = 9.0 Hz), 8.02 (s, 2H).
化合物Ii-137
1H-NMR (DMSO-d6) δ: 0.95-1.12 (m, 2H), 1.13-1.30 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.65-1.95 (m, 5H), 2.93-3.12 (m, 1H), 2.97 (q, 2H, J = 7.2 Hz), 3.25-3.40 (m, 2H), 5.07-5.16 (m, 2H), 7.01 (d, 1H, J = 7.5 Hz), 7.25 (t, 1H, J = 6.0 Hz), 7.92-8.03 (m, 3H), 8.33 (d, 1H, J = 6.0 Hz).
化合物Ii-138
1H-NMR (DMSO-d6) δ: 0.91-1.26 (m, 4H), 1.19 (t, 3H, J = 7.5 Hz), 1.36-1.43 (m, 1H), 1.78-1.90 (m, 4H), 2.90-3.07 (m, 3H), 2.96 (q, 2H, J = 7.5 Hz), 5.69 (t, 1H, J = 5.7 Hz), 5.81 (d, 1H, J = 2.4 Hz), 7.00 (d, 1H, J = 7.8 Hz), 7.16-7.39 (m, 3H), 7.73-7.79 (m, 1H), 7.86-7.88 (m, 1H).
化合物Ii-139
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 4H), 1.20 (s, 3H), 1.22 (s, 3H), 1.40−1.52 (m, 1H), 1.81 (d, 2H, J = 12.4 Hz), 1.88 (d, 2H, J = 12.4 Hz), 2.90-2.98 (m, 2H), 2.99-3.13 (m, 2H), 5.68 (t, 1H, J = 5.6 Hz), 5.81 (s, 1H), 6.93 (d, 1H, J = 8.8 Hz), 7.16-7.40 (m, 3H), 7.76 (t, 1H, J = 8.0 Hz), 7.87 (s, 1H).
化合物Ii-140
1H-NMR (DMSO-d6) δ: 0.90-1.06 (m, 4H), 1.26 (s, 9H), 1.40−1.49 (m, 1H), 1.82 (d, 2H, J = 12.4 Hz), 1.91 (d, 2H, J = 12.4 Hz), 2.90-2.99 (m, 2H), 3.01-3.06 (m, 1H), 5.67 (t, 1H, J = 6.0 Hz), 5.81 (s, 1H), 6.74 (d, 1H, J = 8.4 Hz), 7.14-7.40 (m, 3H), 7.76 (t, 1H, J = 8.4 Hz), 7.87 (s, 1H).
化合物Ii-141
1H-NMR (DMSO-d6) δ: 0.97-1.06 (m, 2H), 1.18-1.27 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.45-1.59 (m, 1H), 1.76-1.81 (m, 2H), 1.87-1.91 (m, 2H), 2.97-3.09 (m, 1H), 3.10-3.13 (m, 1H), 3.17-3.22 (m, 2H), 6.94-7.02 (m, 2H), 6.98 (td, 1H, J = 7.8, 1.2 Hz), 7.36 (dd, 1H, J = 7.8, 0.6 Hz), 7.65 (dd, 1H, J = 7.8, 0.6 Hz), 8.00-8.05 (m, 1H).
化合物Ii-142
1H-NMR (DMSO-d6) δ: 0.96-1.04 (m, 2H), 1.18-1.28 (m, 2H), 1.20 (d, 6H, J = 6.9 Hz), 1.43-1.59 (m, 1H), 1.74-1.79 (m, 2H), 1.85-1.90 (m, 2H), 2.92-3.07 (m, 1H), 3.09-3.18 (m, 3H), 6.92-6.99 (m, 2H), 7.10 (td, 1H, J = 7.8, 1.2 Hz), 7.21 (dd, 1H, J = 7.8, 0.6 Hz), 7.31 (dd, 1H, J = 7.8, 0.6 Hz), 7.89-7.97 (m, 1H).
化合物Ii-143
1H-NMR (DMSO-d6)δ: 0.97-1.07 (m, 2H), 1.17-1.23 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.42-1.57 (m, 1H), 1.73-1.78 (m, 2H), 1.86-1.90 (m, 2H), 2.93-3.02 (m, 1H), 2.97 (q, 2H, J = 7.2 Hz), 3.11 (t, 2H, J = 6.3 Hz), 6.91-7.02 (m, 2H), 7.19 (dd, 1H, J = 8.4, 4.8 Hz), 7.34 (dd, 1H, J = 9.3, 2.4 Hz), 8.00 (t, 1H, J = 6.0 Hz).
化合物Ii-144
1H-NMR (DMSO-d6)δ: 0.97-1.08 (m, 2H), 1.16-1.24 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.42-1.59 (m, 1H), 1.74-1.80 (m, 2H), 1.85-1.90 (m, 2H), 2.92-3.03 (m, 1H), 2.97 (q, 2H, J = 7.5 Hz), 3.18 (t, 2H, J = 6.3 Hz), 6.99-7.07 (m, 2H), 7.33 (dd, 1H, J = 9.0, 4.8 Hz), 7.58 (dd, 1H, J = 8.7, 2.7 Hz), 8.00 (t, 1H, J = 5.4 Hz).
化合物Ii-145
1H-NMR (DMSO-d6) δ: 0.97-1.09 (m, 2H), 1.17-1.23 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.43-1.59 (m, 1H), 1.72-1.81 (m, 2H), 1.85-1.92 (m, 2H), 2.95-3.06 (m, 1H), 2.97 (q, 2H, J = 7.5 Hz), 3.19 (t, 2H, J = 6.0 Hz), 7.01 (d, 1H, J = 8.1 Hz), 7.20-7.23 (m, 1H), 7.33 (dd, 1H, J = 8.7, 0.6 Hz), 7.58 (dd, 1H, J = 2.1, 0.9 Hz), 8.11-8.18 (m, 1H).
化合物Ii-146
1H-NMR (DMSO-d6) δ: 0.98-1.06 (m, 2H), 1.15-1.21 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.42-1.58 (m, 1H), 1.70-1.81 (m, 2H), 1.82-1.96 (m, 2H), 2.93-3.00 (m, 3H), 3.13-3.19 (m, 2H), 6.98-7.02 (m, 2H), 7.26-7.27 (m, 1H), 7.32-7.35 (m, 1H), 8.18-8.21 (m, 1H).
化合物Ii-147
1H-NMR (DMSO-d6) δ: 0.98-1.04 (m, 2H), 1.16-1.23 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.43-1.59 (m, 1H), 1.73-1.78 (m, 2H), 1.86-1.89 (m, 2H), 2.93-3.00 (m, 3H), 3.11-3.15 (m, 2H), 6.72-6.79 (m, 1H), 7.00-7.08 (m, 2H), 7.29-7.34 (m, 1H), 8.13-8.16 (m, 1H).
化合物Ii-148
1H-NMR (DMSO-d6) δ: 0.94-1.06 (m, 2H), 1.15-1.26 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.45-1.58 (m, 1H), 1.72-1.80 (m, 2H), 1.84-1.92 (m, 2H), 2.96 (q, 2H, J = 7.2 Hz), 2.96-3.05 (m, 1H), 3.09-3.16 (m, 2H), 6.99 (d, 1H, J = 8.0 Hz), 7.13 (dd, 1H, J = 8.0, 2.0 Hz), 7.20 (d, 1H, J = 8.4 Hz), 7.49 (d, 1H, J = 2.0 Hz), 8.11 (t, 1H, J = 6.0 Hz).
化合物Ii-149
1H-NMR (DMSO-d6) δ: 0.96-1.08 (m, 2H), 1.12-1.24 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.43-1.59 (m, 1H), 1.74-1.80 (m, 2H), 1.86-1.91 (m, 2H), 2.93-3.01 (m, 3H), 3.17-3.22 (m, 2H), 7.00-7.05 (m, 2H), 7.37-7.39 (m, 1H), 7.65-7.68 (m, 1H), 8.22-8.26 (m, 1H).
化合物Ii-150
1H-NMR (DMSO-d6) δ: 0.98-1.08 (m, 2H), 1.15-1.29 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.44-1.60 (m, 1H), 1.74-1.80 (m, 2H), 1.86-1.91 (m, 2H), 2.95-3.17 (m, 2H), 3.21-3.27 (m, 2H), 6.95-6.98 (m, 1H), 8.10 (dd, 1H, J = 8.4, 2.7 Hz), 8.19 (dd, 1H, J = 3.0, 1.5 Hz), 8.44-8.47 (m, 1H).
化合物Ii-151
1H-NMR (DMSO-d6) δ: 0.99-1.04 (m, 2H), 1.15-1.23 (m, 2H), 1.21 (d, 6H, J = 6.3 Hz), 1.43-1.59 (m, 1H), 1.73-1.81 (m, 2H), 1.85-1.91 (m, 2H), 2.97-3.18 (m, 2H), 3.21-3.29 (m, 2H), 6.95-6.98 (m, 1H), 8.20-8.23 (m, 2H), 8.58-8.61 (m, 1H).
化合物Ii-152
1H-NMR (DMSO-d6) δ: 0.96-1.04 (m, 2H), 1.15-1.26 (m, 2H), 1.25 (s, 9H), 1.56-1.62 (m, 1H), 1.78-1.83 (m, 2H), 1.87-1.93 (m, 2H), 2.98-3.08 (m, 1H), 3.17 (t, 2H, J = 6.3 Hz), 3.48 (s, 3H), 6.47 (d, 2H, J = 8.7 Hz), 6.89-6.96 (m, 2H), 7.11-7.19 (m, 2H).
化合物Ii-153
1H-NMR (DMSO-d6) δ: 0.95-1.04 (m, 2H), 1.13-1.30 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.41 (m, 1H), 1.71-1.94 (m, 4H), 2.80-2.89 (m, 2H), 2.92-3.10 (m, 2H), 2.97 (q, 2H, J = 7.5 Hz), 3.21-3.30 (m, 2H), 6.25-6.35 (m, 2H), 6.39 (dd, 1H, J = 8.4, 2.1 Hz), 7.01 (d, 1H, J = 7.5 Hz), 7.01 (dd, 1H, J = 8.4, 8.4 Hz).
化合物Ii-154
1H-NMR (DMSO-d6) δ: 0.91-1.09 (m, 2H), 1.16-1.28 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.42 (m, 1H), 1.74-1.95 (m, 4H), 2.80-3.16 (m, 9H), 2.97 (q, 2H, J = 7.5 Hz), 6.24-6.36 (m, 2H), 6.30 (dd, 1H, J = 8.4, 2.1 Hz), 7.10 (dd, 1H, J = 8.4, 2.1 Hz), 7.05 (d, 1H, J = 8.4 Hz).
化合物Ii-155
化合物Ii-156
化合物Ii-157
化合物Ii-158
1H-NMR (DMSO-d6) δ: 0.91-1.07 (m, 2H), 1.10-1.30 (m, 5H), 1.41 (m, 1H), 1.76-1.94 (m, 4H), 2.74-2.83 (m, 2H), 2.83 (s, 3H), 2.90-3.08 (m, 3H), 2.96 (s, 3H), 5.68 (m, 1H), 6.39 (m, 1H), 6.58 (m, 1H), 6.95 (dd, 1H, J = 8.4, 8.4 Hz), 7.00 (d, 1H, J = 7.8 Hz).
化合物Ii-159
化合物Ii-160
化合物Ii-161
化合物Ii-162
化合物Ii-163
化合物Ii-164
化合物Ii-165
化合物Ii-166
化合物Ii-167
化合物Ii-168
化合物Ii-169
化合物Ii-170
化合物Ii-171
化合物Ii-172
化合物Ii-173
1H-NMR (DMSO-d6) δ: 0.95-1.08 (m, 2H), 1.15-1.28 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz),1.43 (m, 1H), 1.76-1.85 (m, 2H), 1.85-1.93 (m, 2H), 2.76-2.82 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 2.97 (t, 2H, J = 7.2 Hz), 3.00 (m, 1H), 3.64-3.70 (m, 4H), 6.33 (m, 1H), 6.37 (d, 1H, J = 8.4 Hz), 6.56 (s, 1H), 7.00 (d, 1H, J = 7.8 Hz), 7.28 (d, 1H, J = 8.4 Hz).
化合物Ii-174
化合物Ii-175
化合物Ii-176
化合物Ii-177
化合物Ii-178
化合物Ii-179
化合物Ii-180
化合物Ii-181
化合物Ii-182
化合物Ii-183
化合物Ii-184
化合物Ii-185
化合物Ii-186
化合物Ii-187
化合物Ii-188
化合物Ii-189
化合物Ii-190
化合物Ii-191
化合物Ii-192
化合物Ii-193
化合物Ii-194
化合物Ii-195
化合物Ii-196
化合物Ii-197
化合物Ii-198
化合物Ii-199
化合物Ii-200
化合物Ii-201
化合物Ii-202
化合物Ii-203
化合物Ii-204
化合物Ii-205
化合物Ii-206
1H-NMR (DMSO-d6) δ: 0.98-1.24 (m, 4H), 1.19 (t, 3H, J = 7.5 Hz), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 2.02-2.14 (m, 2H), 2.80 (t, 2H, J = 6.0 Hz), 2.86 (q, 2H, J = 7.2 Hz), 3.64-3.82 (m, 1H), 6.40 (d, 2H, J = 8.1 Hz), 7.01 (d, 2H, J = 7.2 Hz), 7.32-7.50 (m, 4H), 7.99 (d, 2H, J = 6.9 Hz)
化合物Ij-3
1H-NMR (DMSO-d6) δ: 0.96-1.26 (m, 4H), 1.18 (t, 3H, J = 7.5 Hz), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 2.02-2.14 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60-3.78 (m, 1H), 6.40-6.50 (m,2H), 6.85-6.92 (m, 1H), 6.97-7.03 (m, 1H), 7.22-7.35 (m, 2H), 7.36-7.46 (m, 2H), 7.88-7.96 (m, 1H)
化合物Ij-4
1H-NMR (DMSO-d6) δ: 0.92-1.24 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.38 (m, 1H), 1.78-1.88 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60-3.78 (m, 1H), 6.50 (t, 1H, J = 3.9 Hz), 6.53 (s, 1H), 7.00 (t, 1H, J = 5.7 Hz), 7.25 (t, 1H, J = 7.2 Hz), 7.34-7.45 (m, 2H), 7.55 (d, 2H, J = 7.2 Hz), 7.67 (dd, 1H, J = 8.7, 2.7 Hz), 8.29 (d, 1H, J = 2.7 Hz)
化合物Ij-5
1H-NMR (DMSO-d6) δ: 0.92-1.24 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.38 (m, 1H), 1.78-1.88 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60-3.78 (m, 1H), 6.52 (d, 1H, J = 8.4 Hz), 6.60 (d, 1H, J = 7.8 Hz), 7.01 (t, 1H, J = 5.7 Hz), 7.20-7.36 (m, 3H), 7.46 (t, 1H, J = 8.1 Hz), 7.55 (d, 1H, J = 8.7 Hz), 8.15 (s, 1H)
化合物Ij-6
1H-NMR (DMSO-d6) δ: 0.92-1.24 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60-3.78 (m, 1H), 6.51 (d, 1H, J = 8.7 Hz), 6.60 (d, 1H, J = 7.5 Hz), 7.01 (t, 1H, J = 5.7 Hz), 7.02-7.12 (m, 1H), 7.36-7.48 (m, 3H), 7.71 (dd, 1H, J = 8.7, 2.1 Hz), 8.33 (d, 1H, J = 2.1 Hz)
化合物Ij-7
1H-NMR (DMSO-d6) δ: 0.92-1.24 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.5 Hz), 3.60-3.78 (m, 1H), 6.50 (d, 2H, J = 8.7 Hz), 6.99 (t, 1H, J = 6.0 Hz), 7.16-7.26 (m, 2H), 7.52-7.68 (m, 3H), 8.25 (s, 1H)
化合物Ij-8
1H-NMR (CDCl3) δ: 1.15-1.26 (m, 4H), 1.40 (t, 3H, J = 7.5 Hz), 1.55-1.58 (m, 1H), 1.93 (d, 2H, J = 9.7 Hz), 2.23 (d, 2H, J = 9.7 Hz), 3.01-3.11 (m, 4H), 3.56-3.61 (m, 1H), 3.84 (s, 3H), 4.34 (t, 1H, J = 6.1 Hz), 4.83-4.86 (m, 1H), 6.46 (d, 1H, J = 8.6 Hz), 6.99 (d, 1H, J = 8.5 Hz), 7.05 (d, 1H, J = 8.5 Hz), 7.29 (s, 1H), 7.30-7.34 (m, 1H), 7.69 (dd, 1H, J = 8.7, 2.4 Hz), 8.25 (s, 1H).
化合物Ij-9
1H-NMR (CDCl3) δ: 1.16-1.24 (m, 4H), 1.40 (t, 3H, J = 6.2 Hz), 1.55-1.59 (m, 1H), 1.94 (d, 2H, J = 11.8 Hz), 2.23 (d, 2H, J = 11.8 Hz), 3.03-3.09 (m, 4H), 3.58-3.62 (m, 1H), 3.88 (s, 3H), 4.29 (t, 1H, J = 6.4 Hz), 4.85-4.89 (m, 1H), 6.49 (d, 1H, J = 8.7 Hz), 6.88 (dd, 1H, J = 8.7, 2.2 Hz), 7.04-7.06 (m, 1H), 7.10 (d, 1H, J = 8.7 Hz), 7.36 (t, 1H, J = 7.9 Hz), 7.70 (dd, 1H, J = 8.7, 2.2 Hz), 8.32 (s, 1H).
化合物Ij-10
1H-NMR (CDCl3) δ: 1.19-1.30 (m, 4H), 1.41 (t, 3H, J = 6.3 Hz), 1.56-1.59 (m, 1H), 1.94 (d, 2H, J = 11.1 Hz), 2.23 (d, 2H, J = 11.1 Hz), 3.01-3.11 (m, 4H), 3.57-3.61 (m, 1H), 3.87 (s, 3H), 4.27 (t, 1H, J = 6.4 Hz), 4.98 (s, 1H), 6.50 (dd, 1H, J = 8.7, 2.2 Hz), 6.99 (d, 2H, J = 8.9 Hz), 7.43 (d, 2H, J = 8.7 Hz), 7.68 (dd, 1H, J = 8.7, 2.2 Hz), 8.25 (s, 1H).
化合物Ij-11
1H-NMR (DMSO-d6) δ: 0.93-1.08 (m, 2H), 1.09-1.25 (m, 5H), 1.39 (m, 1H), 1.75-1.86 (m, 2H), 1.95-2.07 (m, 2H), 2.34 (s, 3H), 2.78 (t, 2H, J = 6.2 Hz), 2.98 (q, 2H, J = 7.3 Hz), 3.65 (m, 1H), 6.45-6.53 (m, 2H), 7.01 (t, 1H, J = 5.6 Hz), 7.07 (d, 1H, J = 7.1 Hz), 7.23-7.38 (m, 3H), 7.64 (dd, 1H, J1 = 8.8 Hz, J2 = 2.5 Hz), 8.26 (d, 1H, J = 2.5 Hz).
化合物Ij-12
1H-NMR (DMSO-d6) δ: 0.93-1.08 (m, 2H), 1.09-1.27 (m, 11H), 1.39 (m, 1H), 1.76-1.87 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.2 Hz), 2.84-3.03 (m, 3H), 3.66 (m, 1H), 6.45-6.54 (m, 2H), 7.01 (t, 1H, J = 5.8 Hz), 7.13 (d, 1H, J = 6.9 Hz), 7.27-7.41 (m, 3H), 7.66 (dd, 1H, J1 = 8.8 Hz, J2 = 2.5 Hz), 8.27 (d, 1H, J = 2.2 Hz).
化合物Ij-13
1H-NMR (DMSO-d6) δ: 0.92-1.09 (m, 2H), 1.09-1.25 (m, 5H), 1.39 (m, 1H), 1.76-1.85 (m, 2H), 1.95-2.06 (m, 2H), 2.78 (t, 2H, J = 6.2 Hz), 2.98 (q, 2H, J = 7.3 Hz), 3.68 (m, 1H), 6.52 (d, 1H, J = 8.8 Hz), 6.66 (d, 1H, J = 8.0 Hz), 7.02 (t, 1H, J = 5.5 Hz), 7.23 (d, 1H, J = 8.1 Hz), 7.49-7.55 (m, 2H), 7.62 (d, 1H, J1 = 8.5 Hz), 7.72 (dd, 1H, J1 = 8.8 Hz, J2 = 2.5 Hz), 8.35 (d, 1H, J = 2.5 Hz).
化合物Ij-14
1H-NMR (DMSO-d6) δ: 0.92-1.22 (m, 4H), 1.22 (d, 6H, J = 6.4 Hz), 1.39 (m, 1H), 1.76-1.86 (m, 2H), 1.95-2.03 (m, 2H), 2.81 (t, 2H, J = 6.4 Hz), 3.10-3.20 (m, 1H), 3.60-3.75 (m, 1H), 6.65 (d, 1H, J = 4.8 Hz), 6.70 (s, 1H), 6.88-6.98 (m, 2H), 8.16 (d, 1H, J = 5.2 Hz).
化合物Ij-15
1H-NMR (CDCl3) δ: 1.02-1.28 (m, 4H), 1.38 (d, 6H, J = 6.9 Hz), 1.52 (m, 1H), 1.85-1.94 (m, 2H), 2.11-2.21 (m, 2H), 3.01 (t, 2H, J = 6.6 Hz), 3.10-3.25 (m, 1H), 3.38-3.54 (m, 1H), 4.22 (t, 1H, J = 6.3 Hz), 4.58 (d, 1H, J = 7.8 Hz), 6.34 (d, 1H, J = 1.8 Hz), 6.53 (dd, 1H, J = 5.4, 1.8 Hz), 7.93 (d, 1H, J = 5.4 Hz).
化合物Ij-16
1H-NMR (CDCl3) δ: 1.03-1.28 (m, 4H), 1.37 (d, 6H, J = 6.9 Hz), 1.52 (m, 1H), 1.84-1.93 (m, 2H), 2.11-2.21 (m, 2H), 3.01 (t, 2H, J = 6.6 Hz), 3.09-3.24 (m, 1H), 3.40-3.54 (m, 1H), 4.26 (t, 1H, J = 6.6 Hz), 4.44 (d, 1H, J = 8.1 Hz), 6.29 (d, 1H, J = 8.7 Hz), 7.33 (dd, 1H, J = 8.7, 2.7 Hz), 7.99 (d, 1H, J = 2.7 Hz).
化合物Ij-17
1H-NMR (DMSO-d6) δ: 0.92-1.22 (m, 4H), 1.21 (d, 6H, J = 6.8 Hz), 1.36 (m, 1H), 1.76-1.84 (m, 2H), 1.92-2.00 (m, 2H), 2.80 (t, 2H, J = 6.4 Hz), 3.08-3.18 (m, 1H), 3.45-3.56 (m, 1H), 6.36 (d, 1H, J = 8.4 Hz), 6.43 (d, 1H, J = 7.2 Hz), 6.75 (d, 1H, J = 7.6 Hz), 6.94 (t, 1H, J = 6.0 Hz), 7.33 (t, 1H, J = 7.6 Hz).
化合物Ij-18
1H-NMR (DMSO-d6) δ: 0.98-1.24 (m, 4H), 1.22 (d, 6H, J = 6.9 Hz), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.14 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.10-3.22 (m, 1H), 3.64-3.82 (m, 1H), 6.40 (d, 2H, J = 8.4 Hz), 6.95-7.05 (m, 2H), 7.35-7.50 (m, 4H), 7.99 (d, 2H, J = 7.2 Hz)
化合物Ij-19
1H-NMR (CDCl3) δ: 1.22-1.38 (m, 4H), 1.38 (d, 6H, J = 8.0 Hz), 1.54 (m, 1H), 1.86-1.95 (m, 2H), 2.18-2.26 (m, 2H), 3.03 (t, 2H, J = 6.0 Hz), 3.12-3.22 (m, 1H), 3.52-3.64 (m, 1H), 4.16 (t, 1H, J = 6.4 Hz), 4.82-4.92 (m, 1H), 6.46 (d, 1H, J = 8.0 Hz), 7.10-7.20 (m, 2H), 7.23-7.33 (m, 1H), 7.37 (t, 1H, J = 8.0 Hz), 7.65 (d, 1H, J = 8.7 Hz), 8.24 (s, 1H).
化合物Ij-20
1H-NMR (CDCl3) δ: 1.22-1.38 (m, 4H), 1.39 (d, 6H, J = 8.0 Hz), 1.54 (m, 1H), 1.86-1.95 (m, 2H), 2.18-2.26 (m, 2H), 3.03 (t, 2H, J = 6.0 Hz), 3.12-3.22 (m, 1H), 3.52-3.64 (m, 1H), 4.16 (t, 1H, J = 6.4 Hz), 4.78-4.88 (m, 1H), 6.46 (d, 1H, J = 8.0 Hz), 6.98(t, 1H, J = 5.7 Hz), 7.18 (d, 1H, J = 8.0 Hz), 7.23-7.29 (m, 1H), 7.33-7.40 (m, 1H), 7.65 (d, 1H, J = 8.7 Hz), 8.29 (s, 1H).
化合物Ij-21
1H-NMR (CDCl3) δ: 1.10-1.30 (m, 4H), 1.38 (d, 6H, J = 8.0 Hz), 1.54 (m, 1H), 1.86-1.95 (m, 2H), 2.18-2.26 (m, 2H), 3.03 (t, 2H, J = 6.0 Hz), 3.13-3.22 (m, 1H), 3.52-3.64 (m, 1H), 4.15 (t, 1H, J = 6.4 Hz), 4.78-4.88 (m, 1H), 6.46 (d, 1H, J = 8.0 Hz), 7.07-7.14 (m, 2H), 7.40-7.46 (m, 2H), 7.62 (d, 1H, J = 8.7 Hz), 8.23 (s, 1H).
化合物Ij-22
1H-NMR (DMSO-d6) δ: 0.95-1.25 (m, 4H), 1.22 (d, 6H, J = 6.6 Hz), 1.25-1.50 (br, 1H), 1.81 (d, 2H, J = 11.4 Hz), 2.00 (d, 2H, J = 10.5 Hz), 2.81 (t, 2H, J = 6.6 Hz), 3.05-3.22 (m, 1H), 3.58-3.80 (m, 1H), 3.76 (s, 3H), 6.49 (d, 2H, J = 8.7 Hz), 6.50-6.70 (br, 1H), 6.95-7.10 (m, 3H), 7.20-7.32 (m, 2H), 7.51 (d, 1H, J = 7.2Hz), 8.05 (br, 1H). ESI(positive) 418.3 [M+H]+
化合物Ij-23
1H-NMR (DMSO-d6) δ: 0.95-1.32 (m, 4H), 1.22 (d, 6H, J = 6.6 Hz), 1.25-1.55 (br, 1H), 1.82 (d, 2H, J = 11.4 Hz), 2.01 (d, 2H, J = 10.2 Hz), 2.81 (t, 2H, J = 6.6 Hz), 3.05-3.22 (m, 1H), 3.58-3.78 (m, 1H), 3.80 (s, 3H), 6.59 (d, 2H, J = 9.6 Hz), 6.85 (dd, 1H, J = 8.4 Hz, 2.4 Hz), 6.99 (t, 3H, J = 5.7Hz), 7.05-7.18 (m, 2H), 7.32 (d, 1H, J = 7.8Hz), 7.76 (d, 1H, J = 8.4Hz), 8.27 (d, 1H, J = 2.1 Hz). ESI(positive) 418.3 [M+H]+
化合物Ij-24
1H-NMR (DMSO-d6) δ: 0.92-1.25 (m, 4H), 1.22 (d, 6H, J = 6.6 Hz), 1.28-1.48 (m, 1H), 1.81 (d, 2H, J = 10.8 Hz), 2.00 (d, 2H, J = 9.6 Hz), 2.81 (t, 2H, J = 6.6 Hz), 3.08-3.22 (m, 1H), 3.58-3.74 (m, 1H), 3.77 (s, 3H), 6.51 (d, 2H, J = 8.7 Hz), 6.97 (d, 2H, J = 8.7 Hz), 6.98 (brs, 1H), 7.48 (d, 2H, J = 8.7 Hz), 7.63 (dd, 1H, J = 11.4Hz, 2.4Hz), 8.21 (d, 1H, J = 2.4 Hz). ESI(positive) 418.3[M+H]+
化合物Ij-25
1H-NMR (DMSO-d6) δ: 0.92-1.22 (m, 4H), 1.27 (s, 9H), 1.38 (m, 1H), 1.78-1.88 (m, 2H), 1.95-2.05 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.60-3.80 (m, 1H), 6.65 (d, 1H, J = 5.4 Hz), 6.70 (s, 1H), 6.87 (t, 1H, J = 6.0 Hz), 6.94 (d, 1H, J = 7.8 Hz), 8.16 (d, 1H, J = 5.4 Hz)
化合物Ij-26
1H-NMR (DMSO-d6) δ: 0.92-1.22 (m, 4H), 1.27 (s, 9H), 1.38 (m, 1H), 1.78-1.88 (m, 2H), 1.94-2.04 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.60-3.80 (m, 1H), 6.53 (d, 1H, J = 8.7 Hz), 6.87 (t, 1H, J = 5.7 Hz), 7.19 (d, 1H, J = 7.5 Hz), 7.59 (dd, 1H, J = 9.0, 2.4 Hz), 8.26 (d, 1H, J = 2.4 Hz)
化合物Ij-27
1H-NMR (DMSO-d6) δ: 0.92-1.22 (m, 4H), 1.26 (s, 9H), 1.38 (m, 1H), 1.76-1.86 (m, 2H), 1.92-2.02 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.40-3.60 (m, 1H), 6.36 (d, 1H, J = 8.1 Hz), 6.43 (d, 1H, J = 6.9 Hz), 6.80 (d, 1H, J = 7.5 Hz), 6.86 (t, 1H, J = 5.4 Hz), 7.34 (t, 1H, J = 8.4 Hz)
化合物Ij-28
1H-NMR ((DMSO-d6) δ: 0.93-1.18 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.39 (m, 1H), 1.75-1.86 (m, 2H), 1.94-2.05 (m, 2H), 2.80 (t, 2H, J = 6.0 Hz), 3.09-3.27 (m, 2H), 6.19 (d, 1H, J = 8.1 Hz), 6.64 (d, 2H, J = 8.7 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.33 (d, 2H, J = 8.7 Hz) Mass:379[M+H]+
化合物Ij-29
1H-NMR (DMSO-d6) δ: 0.93-1.18 (m, 4H), 1.22 (s, 3H), 1.24 (s, 3H), 1.32-1.49 (m, 2H), 1.82 (d, 2H, J = 11.2 Hz), 2.04 (d, 2H, J = 11.2 Hz), 2.75-2.87 (m, 2H), 3.07-3.28 (m, 2H), 6.64 (s, 1H), 6.96 (s, 1H), 7.10-7.22 (m, 2H), 7.25-7.39 (m, 2H), 7.77-7.90 (m, 2H), 8.63 (s, 1H). 融点:161-162℃
化合物Ij-30
1H-NMR (DMSO-d6) δ: 0.92-1.22 (m, 4H), 1.27 (s, 9H), 1.37 (m, 1H), 1.76-1.86 (m, 2H), 1.94-2.05 (m, 2H), 2.88 (t, 2H, J = 6.3 Hz), 3.19 (m, 1H), 6.19 (d, 1H, J = 7.5 Hz), 6.64 (d, 2H, J = 8.7 Hz), 6.88 (d, 1H, J = 6.0Hz), 7.33 (d, 2H, J = 8.7 Hz) Mass:392M+
化合物Ij-31
1H-NMR (DMSO-d6) δ: 0.92-1.16 (m, 4H), 1.26 (s, 9H), 1,36 (m, 1H), 1.72-1.83 (m, 2H), 1.92-2.02 (m, 2H), 2.87 (t, 2H, J = 6.3 Hz), 3.12 (m, 1H), 6.09-6.23 (m, 4H), 6.87 (t, 1H, J = 6.0 Hz) Mass:361[M+H]+
化合物Ij-32
1H-NMR (CDCl3) δ: 1.00-1.20 (m, 4H), 1.40 (s, 9H), 1.42-1.64 (m, 2H), 1.84-1.95 (m, 2H), 2.09-2.20 (m, 2H), 3.07 (m, 1H), 3.07 (t, 2H, J = 6.3 Hz), 3.90 (m, 1H), 6.10 (dd, 2H, J = 9.6, 5.4 Hz).
化合物Ij-33
1H-NMR (DMSO-d6) δ: 0.93-1.21 (m, 5H), 1.28 (s, 9H), 1.33-1.46 (m, 1H), 1.82 (d, 2H, J = 11.6 Hz), 2.04 (d, 2H, J = 11.6 Hz), 2.86-2.95 (m, 2H), 3.03-3.29 (m, 1H), 6.59-6.71 (m, 1H), 6.80-6.92 (m, 1H), 7.09-7.21 (m, 2H), 7.27-7.37 (m, 2H), 7.77-7.88 (m, 2H), 8.58-8.67 (s, 1H). 融点:172-173℃
化合物Ij-34
1H-NMR (DMSO-d6) δ: 0.96-1.08 (m, 2H), 1.12-1.24(m, 2H), 1.21 (d, 6H, J = 6.4 Hz), 1.38 (m, 1H), 1.76-1.86 (m, 2H), 1.92-2.00 (m, 2H), 2.80 (t, 2H, J = 6.4 Hz), 3.10-3.20 (m, 1H), 3.48-3.60 (m, 1H), 6.95 (t, 1H, J = 5.6 Hz), 7.41 (d, 1H, J = 7.6 Hz), 7.63 (s, 1H), 7.82 (s, 1H).
化合物Ij-35
1H-NMR (DMSO-d6) δ: 0.96-1.26 (m, 4H), 1.27 (s, 9H), 1.38 (m, 1H), 1.78-1.88 (m, 2H), 1.92-2.02 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.48-3.62 (m, 1H), 6.87 (t, 1H, J = 6.0 Hz), 7.45 (d, 1H, J = 7.5 Hz), 7.63 (s, 1H), 7.82 (s, 1H)
化合物Ij-36
1H-NMR (DMSO-d6) δ: 0.96-1.06 (m, 2H), 1.12-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.39 (m, 1H), 1.78-1.84 (m, 2H), 1.95-1.99 (m, 2H), 2.81 (t, 2H, J = 6.0 Hz), 3.10-3.20 (m, 1H), 3.74-3.88 (m, 1H), 6.80 (s, 1H), 6.98 (t, 1H, J = 6.0 Hz), 7.93 (d, 2H, J = 7.2 Hz), 8.53 (s, 1H).
化合物Ij-37
1H-NMR (DMSO-d6) δ: 0.96-1.30 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.80 (t, 2H, J = 6.0 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.72-3.90 (m, 1H), 6.85 (d, 1H, J = 9.6 Hz), 6.93 (d, 1H, J = 7.5 Hz), 7.04 (t, 1H, J = 5.7 Hz), 7.26-7.38 (m, 2H), 7.40-7.52 (m, 1H), 7.57 (d, 1H, J = 9.0 Hz), 7.85 (t, 1H, J =7.8 Hz)
化合物Ij-38
1H-NMR (DMSO-d6) δ: 0.96-1.30 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.80 (t, 2H, J = 6.0 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.72-3.90 (m, 1H), 3.80 (s, 3H), 6.72 (d, 1H, J = 7.8 Hz), 6.77 (d, 1H, J = 9.0 Hz), 6.98-7.10 (m, 2H), 7.12 (d, 1H, J = 8.4 Hz), 7.38 (t, 1H, J = 8.1 Hz), 7.56 (d, 1H, J = 9.3 Hz), 7.61 (d, 1H, J = 7.8 Hz)
化合物Ij-39
1H-NMR (DMSO-d6) δ: 0.96-1.30 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.72-3.90 (m, 1H), 6.85 (d, 1H, J = 9.6 Hz), 6.92 (d, 1H, J = 7.5 Hz), 7.04 (t, 1H, J = 5.7 Hz), 7.21 (t, 1H, J = 8.7 Hz), 7.46-7.56 (m, 1H), 7.75-7.88 (m, 3H)
化合物Ij-40
1H-NMR (DMSO-d6) δ: 0.96-1.10 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.15-1.26 (m, 2H), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.14 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.76-3.87 (m, 1H), 6.85 (d, 1H, J = 9.6 Hz), 6.91 (d, 1H, J = 7.5 Hz), 7.01 (t, 1H, J = 5.7 Hz), 7.42-7.52 (m, 2H), 7.83 (d, 1H, J = 8.0 Hz), 7.93 (d, 1H, J = 8.0 Hz), 8.02 (s, 1H).
化合物Ij-41
1H-NMR (DMSO-d6) δ: 0.96-1.30 (m, 4H), 1.20 (t, 3H, J = 7.5 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.76-3.90 (m, 1H), 6.88 (d, 1H, J = 9.3 Hz), 6.97 (d, 1H, J = 7.5 Hz), 7.03 (t, 1H, J = 5.7 Hz), 7.67-7.77 (m, 2H), 7.92 (d, 1H, J = 9.6 Hz), 8.26 (d, 1H, J = 6.9 Hz), 8.33(s, 1H)
化合物Ij-42
1H-NMR (DMSO-d6) δ: 0.93-1.10 (m, 2H), 1.20 (t, 3H, J= 7.2 Hz), 1.22-1.28 (m, 1H), 1.35-1.50 (m, 2H), 1.84 (d, 2H, J = 12.0 Hz), 2.08 (d, 2H, J = 12.0 Hz), 2.63-2.76 (m, 2H), 2.91-3.03 (m, 2H), 3.75-3.90 (m, 1H), 6.86 (d, 1H, J = 9.2 Hz), 6.93 (d, 1H, J = 7.2 Hz), 6.98-7.07 (m, 1H), 7.36 (d, 1H, J = 7.2 Hz), 7.59 (t, 1H, J = 8.0 Hz), 7.85 (d, 1H, J = 9.2 Hz), 7.91-8.02 (m, 2H). 融点:144-145℃
化合物Ij-43
1H-NMR (DMSO-d6) δ: 0.94-1.06 (m, 2H), 1.10-1.24 (m, 2H), 1.21 (d, 6H, J = 6.8 Hz), 1.39 (m, 1H), 1.76-1.86 (m, 2H), 1.98-2.06 (m, 2H), 2.81 (t, 2H, J = 6.4 Hz), 3.10-3.20 (m, 1H), 3.62-3.74 (m, 1H), 6.84 (d, 1H, J =9.2 Hz), 6.88-6.98 (m, 2H), 7.31 (d, 1H, J = 9.6 Hz).
化合物Ij-44
1H-NMR (DMSO-d6) δ: 0.94-1.26 (m, 4H), 1.20 (d, 6H, J = 6.6 Hz), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.06-3.20 (m, 1H), 3.72-3.90 (m, 1H), 6.75-6.88 (m, 2H), 6.97 (t, 1H, J = 6.0 Hz), 7.30-7.48 (m, 3H), 7.76 (d, 1H, J = 9.3 Hz), 7.94 (d, 2H, J =8.4 Hz)
化合物Ij-45
1H-NMR (DMSO-d6) δ: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.9 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.3 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 6.85 (d, 1H, J = 9.0 Hz), 6.91 (d, 1H, J = 7.5 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.25-7.36 (m, 2H), 7.40-7.50 (m, 1H), 7.57 (d, 1H, J = 6.9 Hz), 7.85 (t, 1H, J =8.1 Hz)
化合物Ij-46
1H-NMR (DMSO-d6) δ: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.6 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.3 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 6.85 (d, 1H, J = 9.3 Hz), 6.90 (d, 1H, J = 7.5 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.21 (t, 1H, J = 7.8 Hz), 7.46-7.56 (m, 1H), 7.75-7.86 (m, 3H)
化合物Ij-47
1H-NMR (DMSO-d6) δ: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.9 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 6.81 (d, 1H, J = 7.5 Hz), 6.84 (d, 1H, J = 9.3 Hz), 6.98 (t, 1H, J = 6.3 Hz), 7.25-7.35 (m, 2H), 7.77 (d, 1H, J = 9.3 Hz), 7.96-8.06 (m, 2H)
化合物Ij-48
1H-NMR (DMSO-d6) δ: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.9 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.3 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 3.80 (s, 3H), 6.71 (d, 1H, J = 7.8 Hz), 6.76 (d, 1H, J = 9.3 Hz), 6.98 (t, 1H, J = 5.7 Hz), 7.05 (d, 1H, J = 7.2 Hz), 7.12 (d, 1H, J = 7.8 Hz), 7.38 (t, 1H, J = 8.4 Hz), 7.56 (d, 1H, J = 9.3 Hz), 7.62 (d, 1H, J = 6.9 Hz)
化合物Ij-49
1H-NMR (DMSO-d6) δ: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.6 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 3.82 (s, 3H), 6.78-6.88 (m, 2H), 6.92-7.04 (m, 2H), 7.37 (t, 1H, J = 7.5 Hz), 7.46-7.58 (m, 2H), 7.79 (d, 1H, J = 9.3 Hz)
化合物Ij-50
1H-NMR (DMSO-d6) δ: 0.96-1.28 (m, 4H), 1.22 (d, 6H, J = 6.9 Hz), 1.42 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.10-3.22 (m, 1H), 3.74-3.92 (m, 1H), 3.80 (s, 3H), 6.70 (d, 1H, J = 7.8 Hz), 6.82 (d, 1H, J = 9.3 Hz), 6.95-7.05 (m, 3H), 7.72 (d, 1H, J = 9.3 Hz), 7.90 (d, 2H, J = 9.0 Hz).
化合物Ij-51
1H-NMR (DMSO-d6) δ: 0.92-1.05 (m, 2H), 1.07-1.20 (m, 2H), 1.22 (d, 6H, J = 6.9 Hz), 1.39 (m, 1H), 1.76-1.85 (m, 2H), 2.02-2.10 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.57-3.68 (m, 1H), 4.89-4.98 (m, 2H), 6.47 (d, 1H, J = 8.0 Hz), 6.88 (d, 1H, J = 7.5 Hz), 6.96 (t, 1H, J = 6.0 Hz), 7.02 (d, 1H, J = 7.5 Hz).
化合物Ij-52
1H-NMR (DMSO-d6) δ: 0.92-1.05 (m, 2H), 1.07-1.20 (m, 2H), 1.22 (d, 6H, J = 6.9 Hz), 1.39 (m, 1H), 1.52-1.74 (m, 6H), 1.77-1.85 (m, 2H), 1.87-1.97 (m, 2H), 2.02-2.09 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.55-3.65 (m, 1H), 5.25-5.32 (m, 1H), 6.19 (d, 1H, J = 8.0 Hz), 6.77 (s, 2H), 6.95 (t, 1H, J = 6.0 Hz).
化合物Ij-53
1H-NMR (DMSO-d6) δ: 0.92-1.15 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.38 (m, 1H), 1.77-1.85 (m, 2H), 1.88-1.95 (m, 4H), 2.02-2.09 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.25-3.35 (m, 4H), 3.55-3.65 (m, 1H), 5.80-5.85 (m, 1H), 6.72 (d, 1H, J = 8.0 Hz), 6.80 (d, 1H, J = 8.0 Hz), 6.96 (t, 1H, J = 6.0 Hz).
化合物Ij-54
1H-NMR (DMSO-d6) δ: 0.92-1.20 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.38 (m, 1H), 1.77-1.85 (m, 2H), 2.02-2.09 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.58-3.65 (m, 1H), 6.56 (d, 1H, J = 8.0 Hz), 6.90-6.98 (m, 2H), 7.03-7.10 (m, 3H), 7.15 (t, 1H, J = 8.0 Hz), 6.38 (t, 2H, J = 8.0 Hz).
化合物Ij-55
1H-NMR (DMSO-d6) δ: 0.92-1.20 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.38 (m, 1H), 1.77-1.85 (m, 2H), 2.02-2.09 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.58-3.65 (m, 1H), 6.55 (d, 1H, J = 8.0 Hz), 6.90-6.98 (m, 2H), 7.05-7.15 (m, 3H), 7.21 (t, 2H, J = 8.0 Hz).
化合物Ij-56
1H-NMR (DMSO-d6) δ: 0.92-1.20 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.38 (m, 1H), 1.77-1.85 (m, 2H), 2.02-2.09 (m, 2H), 2.80 (t, 2H, J = 6.3 Hz), 3.09-3.20 (m, 1H), 3.58-3.65 (m, 1H), 3.75 (s, 3H), 6.49 (d, 1H, J = 8.0 Hz), 6.87-6.98 (m, 4H), 7.00-7.07 (m, 3H).
化合物Ij-57
1H-NMR (DMSO-d6) δ: 0.96-1.28 (m, 4H), 1.27 (s, 9H), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 2.00-2.10 (m, 2H), 2.88 (t, 2H, J = 6.0 Hz), 3.60-3.76 (m, 1H), 6.82-6.92 (m, 2H), 6.96 (d, 1H, J = 7.8 Hz), 7.32 (d, 1H, J = 9.6 Hz).
化合物Ij-58
1H-NMR (DMSO-d6) δ: 0.99-1.28 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.39 (m, 1H), 1.78-1.86 (m, 2H), 2.04-2.10 (m, 2H), 2.82 (t, 2H, J = 6.1 Hz), 3.06-3.20 (m, 1H), 3.80-3.96 (m, 1H), 6.71 (d, 1H, J = 9.0 Hz), 6.76-6.86 (m, 1H), 6.90-6.98 (m, 1H), 7.10 (t, 1H, J = 8.1 Hz), 7.39-7.50 (m, 2H), 7.56 (d, 1H, J = 7.5 Hz), 7.78 (d, 1H, J = 7.5 Hz).
化合物Ij-59
1H-NMR (DMSO-d6) δ: 0.99-1.28 (m, 4H), 1.27 (s, 9H), 1.40 (m, 1H), 1.80-1.85 (m, 2H), 2.04-2.09 (m, 2H), 2.91 (t, 2H, J = 6.1 Hz), 3.80-3.96 (m, 1H), 6.70 (d, 1H, J = 9.0 Hz), 6.81-6.87 (m, 2H), 7.10 (t, 1H, J = 8.1 Hz), 7.39-7.44 (m, 2H), 7.56 (d, 1H, J = 7.5 Hz), 7.79 (d, 1H, J = 7.5 Hz).
化合物Ij-60
1H-NMR (DMSO-d6) δ: 0.97-1.09 (m, 2H), 1.23 (d, 6H, J = 6.9 Hz), 1.31-1.50 (m, 2H), 1.82-1.87 (m, 2H), 2.01-2.05 (m, 2H), 2.83 (t, 2H, J = 6.0 Hz), 3.11-3.20 (m, 1H), 4.00-4.18 (m, 1H), 6.83 (d, 1H, J = 5.7 Hz), 6.90-7.06 (m, 2H), 7.45 (t, 1H, J = 6.9 Hz), 7.59 (t, 1H, J = 8.1 Hz), 7.67 (d, 1H, J = 8.4 Hz), 7.83 (d, 1H, J = 5.7 Hz), 8.27 (d, 1H, J = 7.5 Hz).
化合物Ij-61
1H-NMR (DMSO-d6) δ: 0.96-1.09 (m, 2H), 1.28 (s, 9H), 1.29-1.50 (m, 2H), 1.82-1.87 (m, 2H), 2.01-2.05 (m, 2H), 2.91 (t, 2H, J = 7.8 Hz), 4.00-4.18 (m, 1H), 6.82-6.89 (m, 2H), 6.97 (d, 1H, J = 7.5 Hz ), 7.45 (t, 1H, J = 7.2 Hz), 7.59 (t, 1H, J = 8.1 Hz), 7.67 (d, 1H, J = 7.8 Hz), 7.84 (d, 1H, J = 6.0 Hz), 8.27 (d, 1H, J = 8.4 Hz).
化合物Ij-62
1H-NMR (DMSO-d6) δ: 0.96-1.14 (m, 2H), 1.18-1.30 (m, 2H), 1.22 (d, 6H, J = 6.6 Hz), 1.40 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.14 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.10-3.20 (m, 1H), 3.58-3.70 (m, 1H), 6.95-7.03 (m, 2H), 7.20 (t, 1H, J = 7.5 Hz ), 7.37 (d, 1H, J = 8.1 Hz), 7.64 (d, 1H, J = 7.5 Hz), 7.92 (d, 1H, J = 7.8 Hz).
化合物Ij-63
1H-NMR (DMSO-d6) δ: 1.00 (dd, 2H, J = 24.8, 10.6 Hz), 1.15-1.22 (m, 2H), 1.18 (t, 3H, J = 7.6 Hz), 1.27 (s, 9H), 1.34-1.40 (m, 1H), 1.81 (d, 2H, J = 11.6 Hz), 2.07 (d, 2H, J = 11.6 Hz), 2.60 (q, 2H, J = 7.6 Hz), 2.89 (t, 2H, J = 6.3 Hz), 3.52-3.63 (m, 1H), 6.87 (t, 1H, J = 5.8 Hz), 7.04 (d, 1H, J = 7.9 Hz), 7.27 (d, 1H, J = 8.2 Hz), 7.47 (s, 1H), 7.80 (d, 1H, J = 7.6 Hz).
化合物Ij-64
1H-NMR (DMSO-d6) δ: 0.92-1.10 (m, 2H), 1.12-1.25 (m, 2H), 1.27 (s, 9H), 1.37 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.12 (m, 2H), 2.89 (t, 2H, J = 6.0 Hz), 3.50-3.66 (m, 1H), 6.87 (t, 1H, J = 5.7 Hz), 7.03 (dd, 1H, J = 8.7, 2.7 Hz), 7.32-7.37 (m, 1H), 7.58 (dd, 1H, J = 8.7, 2.7 Hz), 7.92 (d, 1H, J = 7.2 Hz).
化合物Ij-65
1H-NMR (DMSO-d6) δ: 1.01 (dd, 2H, J = 24.6, 10.2 Hz), 1.21 (dd, 2H, J = 24.6, 10.2 Hz), 1.27 (s, 9H), 1.34-1.40 (m, 1H), 1.82 (d, 2H, J = 11.2 Hz), 2.08 (d, 2H, J = 11.2 Hz), 2.89 (t, 2H, J = 6.2 Hz), 3.59-3.65 (m, 1H), 6.87 (t, 1H, J = 5.8 Hz), 7.21 (dd, 1H, J = 8.6, 2.4 Hz), 7.34 (d, 1H, J = 8.6 Hz), 7.77 (d, 1H, J = 1.8 Hz), 8.06 (d, 1H, J = 7.6 Hz).
化合物Ij-66
1H-NMR (CDCl3) δ: 1.09-1.46 (m, 4H), 1.41 (s, 9H), 1.54 (m, 1H), 1.90-2.00 (m, 2H), 2.24-2.34 (m, 2H), 3.09 (t, 2H, J = 6.6 Hz), 3.46-3.60 (m, 1H), 3.99 (t, 1H, J = 6.6 Hz), 6.58 (brs, 1H), 7.58(s, 2H), 7.85 (s, 1H).
化合物Ij-67
1H-NMR (DMSO-d6) δ: 0.90-1.30 (m, 4H), 1.27 (s, 9H), 1.30-1.48 (m, 1H), 1.82 (d, 2H, J = 11.1 Hz), 2.08 (d, 2H, J = 9.6 Hz), 2.89 (t, 2H, J = 6.3 Hz), 3.55-3.70 (m, 1H), 6.87 (t, 1H, J = 5.7 Hz), 7.17 (m, 1H), 7.41 (d, 1H, J = 8.7 Hz), 7.77 (d, 1H, J = 1.5 Hz), 8.10 (d, 1H, J = 7.5 Hz). ESI(positive)m/z 466.2 [M+H]+
化合物Ij-68
1H-NMR (DMSO-d6) δ: 0.90-1.28 (m, 4H), 1.25 (s, 9H), 1.32 (m, 1H), 1.76-1.82 (m, 2H), 2.00-2.10 (m, 2H), 2.87 (t, 2H, J = 6.6 Hz), 3.50-3.62 (m, 1H), 3.71 (s, 3H), 6.77 (dd, 1H, J = 8.7, 2.7 Hz), 6.84 (t, 1H, J = 5.7 Hz), 7.22-7.28 (m, 2H), 7.66 (d, 1H, J = 7.2 Hz).
化合物Ij-69
1H-NMR (DMSO-d6) δ: 0.94-1.10 (m, 2H), 1.12-1.25 (m, 2H), 1.27 (s, 9H), 1.37 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.12 (m, 2H), 2.90 (t, 2H, J = 6.0 Hz), 3.52-3.68 (m, 1H), 3.84 (s, 3H), 6.82 (d, 1H, J = 8.1 Hz), 6.88 (t, 1H, J = 5.4 Hz), 6.95 (t, 1H, J = 7.8 Hz), 7.23 (d, 1H, J = 7.8 Hz), 7.83 (d, 1H, J = 7.8 Hz).
化合物Ij-70
1H-NMR (DMSO-d6) δ: 0.98-1.10 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.17-1.32 (m, 2H), 1.40 (m, 1H), 1.76-1.88 (m, 2H), 2.04-2.14 (m, 2H), 2.79 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.60-3.78 (m, 1H), 7.03 (t, 1H, J = 6.3 Hz), 7.45-7.54 (m, 2H), 8.10 (s, 1H), 8.34 (d, 1H, J = 7.2 Hz).
化合物Ij-71
1H-NMR (DMSO-d6) δ: 1.01 (dd, 2H, J = 26.1, 12.3 Hz), 1.16-1.22 (m, 2H), 1.22 (d, 6H, J = 6.6 Hz), 1.35-1.41 (m, 1H), 1.70-1.77 (m, 1H), 1.82 (d, 2H, J = 11.6 Hz), 2.08 (d, 2H, J = 11.6 Hz), 2.81 (t, 2H, J = 6.3 Hz), 3.66-3.72 (m, 1H), 6.99 (t, 1H, J = 6.3 Hz), 7.23 (dd, 1H, J = 8.1, 4.7 Hz), 7.66 (d, 1H, J = 8.1 Hz), 8.07 (d, 1H, J = 4.7 Hz), 8.26 (d, 1H, J = 6.3 Hz).
化合物Ij-72
1H-NMR (DMSO-d6) δ: 1.01 (dd, 2H, J = 24.8, 11.3 Hz), 1.18-1.23 (m, 2H), 1.27 (s, 9H), 1.36-1.39 (m, 1H), 1.82 (d, 2H, J = 11.5 Hz), 2.08 (d, 2H, J = 11.5 Hz), 2.89 (t, 2H, J = 6.1 Hz), 3.65-3.73 (m, 1H), 6.87 (t, 1H, J = 5.7 Hz), 7.23 (dd, 1H, J = 8.1, 4.8 Hz), 7.66 (d, 1H, J = 7.9 Hz), 8.07 (d, 1H, J = 4.7 Hz), 8.26 (d, 1H, J = 7.6 Hz).
化合物Ij-73
1H-NMR (CDCl3)δ: 1.09-1.46 (m, 4H), 1.41 (s, 9H), 1.55 (m, 1H), 1.92-2.02 (m, 2H), 2.24-2.34 (m, 2H), 3.09 (t, 2H, J = 6.3 Hz), 3.58-3.72 (m, 1H), 3.98 (t, 1H, J = 6.0 Hz), 6.30 (brs, 1H), 7.62(d, 1H, J = 8.1 Hz), 7.77 (d, 1H, J = 8.4 Hz).
化合物Ij-74
1H-NMR (DMSO-d6) δ: 0.90-1.08 (m, 2H), 1.12-1.40 (m, 3H), 1.25 (s, 9H), 1.76-1.86 (m, 2H), 1.98-2.10 (m, 2H), 2.87 (d, 2H, J = 6.3 Hz), 3.40-3.56 (m, 1H), 6.85 (brs, 1H), 6.93 (t, 1H, J = 7.5 Hz), 7.07 (t, 1H, J = 7.5 Hz), 7.20 (d, 1H, J = 7.5 Hz), 7.29 (d, 1H, J = 7.8 Hz), 7.79 (brs, 1H).
化合物Ij-75
1H-NMR (CDCl3) δ: 1.08-1.26 (m, 2H), 1.36-1.60 (m, 3H), 1.40 (s, 9H), 1.92-2.02 (m, 2H), 2.22-2.32 (m, 2H), 3.08 (t, 2H, J = 6.6 Hz), 3.68-3.80 (m, 1H), 4.03 (t, 1H, J = 6.0 Hz), 7.06 (brs, 1H), 7.20-7.36(m, 3H).
化合物Ij-76
1H-NMR (DMSO-d6) δ: 1.02 (dd, 2H, J = 25.2, 12.4 Hz), 1.17 (t, 3H, J = 7.1 Hz), 1.20 (t, 3H, J = 7.3 Hz), 1.26-1.35 (m, 2H), 1.37-1.42 (m, 1H), 1.83 (d, 2H, J = 11.6 Hz), 2.05 (d, 2H, J = 11.6 Hz), 2.80 (t, 2H, J = 6.4 Hz), 2.99 (q, 2H, J = 7.3 Hz), 3.65-3.72 (m, 1H), 4.01 (q, 2H, J = 7.1 Hz), 6.32 (d, 1H, J = 7.9 Hz), 6.86-6.94 (m, 2H), 7.01 (t, 1H, J = 6.0 Hz), 7.12 (d, 1H, J = 6.9 Hz), 7.17 (d, 1H, J = 6.8 Hz).
化合物Ij-77
1H-NMR (DMSO-d6) δ: 1.02 (dd, 2H, J = 24.8, 10.8 Hz), 1.19-1.21 (m, 2H), 1.30 (s, 9H), 1.37-1.41 (m, 1H), 1.84 (d, 2H, J = 10.6 Hz), 2.06 (d, 2H, J = 10.6 Hz), 2.92 (t, 2H, J = 6.3 Hz), 3.50-3.52 (m, 1H), 6.42 (d, 1H, J = 8.1 Hz), 6.83 (d, 1H, J = 7.9 Hz), 6.88-6.92 (m, 2H), 7.11-7.14 (m, 2H), 10.58 (s, 1H).
化合物Ij-78
1H-NMR (DMSO-d6) δ: 0.97-1.05 (m, 2H), 1.20-1.26 (m, 2H), 1.28 (s, 9H), 1.34-1.38 (m, 1H), 1.84 (d, 2H, J = 11.5 Hz), 2.07 (d, 2H, J = 11.5 Hz), 2.90 (t, 2H, J = 6.1 Hz), 3.47 (s, 3H), 3.63-3.69 (m, 1H), 6.34 (d, 1H, J = 7.6 Hz), 6.87-6.93 (m, 3H), 7.11 (d, 1H, J = 8.4 Hz), 7.17 (d, 1H, J = 8.4 Hz).
化合物Ij-79
1H-NMR (DMSO-d6) δ: 1.03 (dd, 2H, J = 23.6, 10.8 Hz), 1.18 (t, 3H, J = 7.5 Hz), 1.25-1.34 (m, 2H), 1.29 (s, 9H), 1.37-1.40 (m, 1H), 1.86 (d, 2H, J = 11.7 Hz), 2.07 (d, 2H, J = 11.7 Hz), 2.92 (t, 2H, J = 6.2 Hz), 3.67-3.73 (m, 1H), 4.03 (q, 2H, J = 7.1 Hz), 6.34 (d, 1H, J = 7.9 Hz), 6.87-6.96 (m, 3H), 7.14 (dd, 1H, J = 8.1, 1.2 Hz), 7.19 (dd, 1H, J = 8.1, 1.2 Hz).
化合物Ij-80
1H-NMR (DMSO-d6) δ: 1.00 (dd, 2H, J = 23.2, 11.9 Hz), 1.19-1.25 (m, 2H), 1.28 (s, 9H), 1.33-1.38 (m, 1H), 1.45 (s, 3H), 1.47 (s, 3H), 1.83 (d, 2H, J = 11.1 Hz), 2.07 (d, 2H, J = 11.1 Hz), 2.90 (t, 2H, J = 6.1 Hz), 3.62-3.70 (m, 1H), 4.57-4.66 (m, 1H), 6.21 (d, 1H, J = 7.9 Hz), 6.82-6.94 (m, 3H), 7.18 (d, 1H, J = 7.6 Hz), 7.31 (d, 1H, J = 7.6 Hz).
化合物Ij-81
化合物Ij-82
1H-NMR (DMSO-d6) δ: 0.90-1.19 (m, 4H), 1.28 (s, 9H), 1.32-1.45 (m, 1H), 1.80 (d, 2H, J = 11.2 Hz), 1.98 (d, 2H, J = 11.2 Hz), 2.84-2.93 (m, 2H), 3.26 (s, 3H), 3.40-3.53 (m, 1H), 6.29 (d, 1H, J = 8.0 Hz), 6.38 (d, 1H, J = 7.2 Hz), 6.86 (s, 1H), 7.33 (d, 1H, J = 8.4 Hz).
化合物Ij-83
化合物Ij-84
1H-NMR (DMSO-d6) δ: 0.92-1.20 (m, 4H), 1.18 (t, 3H, J = 7.2 Hz), 1.40 (m, 1H), 1.75-1.85 (m, 2H), 1.96-2.06 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.60-3.78 (m, 1H), 6.38 (d, 1H, J = 8.1 Hz), 6.67 (s, 1H), 6.72 (d, 1H, J = 5.4 Hz), 7.00 (t, 1H, J = 6.0 Hz), 7.36-7.54 (m, 3H), 7.62 (d, 2H, J = 6.9 Hz), 8.00 (d, 1H, J = 5.4 Hz)
化合物Ij-85
1H-NMR (DMSO-d6) δ: 1.00-1.20 (m, 4H), 1.20 (t, 3H, J = 7.2 Hz), 1.43 (m, 1H), 1.80-1.88 (m, 2H), 2.03-2.13 (m, 2H), 2.81 (t, 3H, J = 6.0 Hz), 3.00 (q, 2H, J = 7.2 Hz), 3.26 (m, 1H), 6.17 (d, 1H, J = 7.6 Hz), 6.57 (s, 1H), 6.96-7.07 (m, 2H), 7.35 (dd, 1H, J = 8.4, 4.0 Hz), 8.02 (d, 1H, J = 8.4 Hz), 8.47 (d, 1H, J = 4.0 Hz).
化合物Ij-86
1H-NMR (DMSO-d6) δ: 1.00-1.24 (m, 4H), 1.23 (d, 6H, J = 6.4 Hz), 1.42 (m, 1H), 1.80-1.88 (m, 2H), 2.03-2.12 (m, 2H), 2.79-2.87 (m, 2H), 3.16 (m, 1H), 3.27 (m, 1H), 6.17 (d, 1H, J = 8.0 Hz), 6.57 (s, 1H), 6.99 (d, 1H, J = 8.0 Hz), 7.01 (s, 1H), 7.35 (dd, 1H, J = 8.0, 4.0 Hz), 8.02 (d, 1H, J = 8.0 Hz), 8.47 (d, 1H, J = 2.8 Hz).
化合物Ij-87
1H-NMR (DMSO-d6) δ: 0.95-1.08 (m, 2H), 1.11-1.25 (m, 2H), 1.20 (t, 3H, J = 7.2 Hz), 1.40 (m, 1H), 1.76-1.86 (m, 2H), 1.97-2.04 (m, 2H), 2.73-2.82 (m, 2H), 2.99 (q, 2H, J = 7.2 Hz), 3.70 (m, 1H), 6.53 (d, 1H, J = 8.8 Hz), 6.53 (d, 1H, J = 8.8 Hz), 7.01 (t, 1H, J = 6.0 Hz), 7.58 (d, 1H, J = 3.2 Hz), 7.79 (d, 1H, J = 3.2 Hz), 7.86 (d, 1H, J = 8.8 Hz), 8.55 (s, 1H).
化合物Ij-88
1H-NMR (DMSO-d6) δ: 0.92-1.07 (m, 2H), 1.09-1.20 (m, 2H), 1.19 (t, 6H, J = 7.2 Hz), 1.39 (m, 1H), 1.75-1.83 (m, 2H), 1.95-2.03 (m, 2H), 2.74-2.81 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.66 (m, 1H), 6.48 (d, 1H, J = 8.4 Hz), 6.60 (d, 1H, J = 7.6 Hz), 7.00 (t, 1H, J = 5.6 Hz), 7.06 (dd, 1H, J = 4.8, 2.4 Hz), 7.25 (d, 1H, J = 2.4 Hz), 7.37 (d, 1H, J = 4.8 Hz), 7.60 (dd, 1H, J = 8.4, 2.0 Hz), 8.26 (s, 1H).
化合物Ij-89
1H-NMR (DMSO-d6) δ: 0.93-1.07 (m, 2H), 1.10-1.20 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.39 (m, 1H), 1.76-1.84 (m, 2H), 1.96-2.04 (m, 2H), 2.73-2.81 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.65 (m, 1H), 6.41-6.50 (m, 2H), 7.01 (t, 1H, J = 6.0 Hz), 7.44 (d, 1H, J = 4.0 Hz), 7.58 (m, 1H), 7.59 (s, 1H), 7.68 (d, 1H, J = 8.0 Hz), 8.34 (s, 1H).
化合物Ij-90
1H-NMR (DMSO-d6) δ: 0.95-1.08 (m, 2H), 1.12-1.25 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.39 (m, 1H), 1.76-1.86 (m, 2H), 1.94-2.03 (m, 2H), 2.75-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.71 (m, 1H), 6.54 (d, 1H, J = 8.8 Hz), 6.98-7.07 (m, 2H), 7.25 (s, 1H), 7.85 (dd, 1H, J = 8.8, 2.0 Hz), 8.07 (s, 1H), 8.56 (d, 1H, J = 2.0 Hz).
化合物Ij-91
1H-NMR (DMSO-d6) δ: 0.93-1.07 (m, 2H), 1.11-1.22 (m, 2H), 1.21 (d, 6H, J = 6.8 Hz), 1.38 (m, 1H), 1.77-1.85 (m, 2H), 1.95-2.03 (m, 2H), 2.77-2.83 (m, 2H), 3.14 (m, 1H), 3.72 (m, 1H), 6.53 (d, 1H, J = 8.8 Hz), 6.97 (t, 1H, J = 6.0 Hz), 7.02 (d, 1H, J = 7.6 Hz), 7.25 (s, 1H), 7.84 (dd, 1H, J = 8.8, 2.0 Hz), 8.06 (s, 1H), 8.56 (d, 1H, J = 2.0 Hz).
化合物Ij-92
1H-NMR (DMSO-d6) δ: 0.92-1.03 (m, 2H), 1.11-1.23 (m, 2H), 1.21 (d, 6H, J = 6.8 Hz), 1.37 (m, 1H), 1.75-1.83 (m, 2H), 1.91-1.99 (m, 2H), 2.36-2.42 (m, 2H), 3.12 (m, 1H), 3.70 (m, 1H), 6.49 (d, 1H, J = 9.2 Hz), 6.97 (t, 1H, J = 6.0 Hz), 7.47 (d, 1H, J = 8.0 Hz), 7.62 (d, 1H, J = 8.0 Hz), 8.36 (s, 1H).
化合物Ij-93
1H-NMR (DMSO-d6) δ: 0.95-1.13 (m, 4H), 1.23 (d, 6H, J = 6.9 Hz), 1.31-1.44 (m, 1H), 1.78-1.82 (m, 2H), 2.03-2.06 (m, 2H), 2.76-2.82 (m, 2H), 3.10-3.19 (m, 1H), 3.20-3.25 (m, 4H), 3.58-3.65 (m, 1H), 3.69-3.74 (m, 4H), 6.04 (d, 1H, J = 7.5 Hz), 6.72 (d, 1H, J = 9.6 Hz), 6.95-6.99 (m, 1H), 7.10 (d, 1H, J = 9.6 Hz).
化合物Ij-94
1H-NMR (DMSO-d6) δ: 0.96-1.42 (m, 5H), 1.22 (d, 6H, J = 6.9 Hz), 1.79-1.83 (m, 2H), 2.03-2.07 (m, 2H), 2.80 (d, 2H, J = 6.3 Hz), 3.10-3.19 (m, 1H), 3.54-3.70 (m, 1H), 3.74 (s, 3H), 6.57-6.64 (m, 3H), 6.72-6.75 (m, 1H), 6.90-7.09 (m, 3H), 7.24-7.30 (m, 1H).
化合物Ij-95
1H-NMR (DMSO-d6) δ: 0.93-1.04 (m, 2H), 1.10-1.18 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.34-1.44 (m, 1H), 1.78-1.87 (m, 2H), 2.02-2.12 (m, 2H), 2.77-2.84 (m, 2H), 3.10-3.20 (m, 1H), 3.52-3.70 (m, 1H), 6.64 (d, 1H, J = 8.0 Hz), 6.88-7.06 (m, 5H), 7.12 (d, 1H, J = 8.0 Hz), 7.37-7.46 (m, 1H).
化合物Ij-96
1H-NMR (DMSO-d6) δ: 0.90-1.04 (m, 2H), 1.05-1.18 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.43 (m, 1H), 1.75-1.84 (m, 2H), 1.98-2.08 (m, 2H), 2.76-2.84 (m, 2H), 3.08-3.18 (m, 1H), 3.52-3.64 (m, 1H), 6.55 (d, 1H, J = 8.0 Hz), 6.91-7.00 (m, 2H), 7.15-7.38 (m, 5H).
化合物Ij-97
1H-NMR (DMSO-d6) δ: 0.96-1.08 (m, 2H), 1.12-1.25 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.35-1.47 (m, 1H), 1.78-1.87 (m, 2H), 2.02-2.10 (m, 2H), 2.78-2.83 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.70-3.82 (m, 1H), 6.82 (d, 1H, J = 8.0 Hz), 6.93 (d, 1H, J = 8.0 Hz), 7.01 (t, 1H, J = 4.5 Hz), 7.13 (d, 1H, J = 4.0 Hz), 7.43 (d, 1H, J = 4.0 Hz), 7.76 (d, 1H, J = 8.0 Hz).
化合物Ij-98
1H-NMR (DMSO-d6) δ: 0.97-1.10 (m, 2H), 1.17-1.28 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.37-1.49 (m, 1H), 1.80-1.88 (m, 2H), 2.04-2.12 (m, 2H), 2.77-2.83 (m, 2H), 2.99 (q, 2H, J = 7.2 Hz), 3.76-3.88 (m, 1H), 6.85 (d, 1H, J = 8.0 Hz), 6.99-7.05 (m, 2H), 7.61 (s, 1H), 7.90 (d, 1H, J = 8.0 Hz), 8.02 (s, 2H).
化合物Ij-99
1H-NMR (DMSO-d6) δ: 0.98-1.10 (m, 2H), 1.14-1.26 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.37-1.48 (m, 1H), 1.80-1.88 (m, 2H), 2.04-2.13 (m, 2H), 2.77-2.83 (m, 2H), 2.96 (s, 6H), 2.99 (q, 2H, J = 7.2 Hz), 3.76-3.86 (m, 1H), 6.72-6.78 (m, 2H), 6.82 (d, 1H, J = 8.0 Hz), 7.02 (t, 1H, J = 4.5 Hz), 7.18 (d, 1H, J = 8.0 Hz), 7.26 (t, 1H, J = 8.0 Hz), 7.34 (s, 1H), 7.74 (d, 1H, J = 8.0 Hz).
化合物Ij-100
1H-NMR (DMSO-d6)δ: 0.98-1.10 (m, 2H), 1.16-1.27 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.37-1.48 (m, 1H), 1.80-1.88 (m, 2H), 2.04-2.13 (m, 2H), 2.77-2.83 (m, 2H), 2.99 (q, 2H, J = 7.2 Hz), 3.76-3.86 (m, 1H), 6.83 (d, 1H, J = 8.0 Hz), 6.89 (d, 1H, J = 8.0 Hz), 7.02 (t, 1H, J = 4.5 Hz), 7.42-7.50 (m, 3H), 7.53-7.59 (m, 2H).
化合物Ij-101
1H-NMR (DMSO-d6)δ: 0.92-1.05 (m, 2H), 1.08-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.36-1.43 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.09 (m, 2H), 2.77-2.83 (m, 2H), 3.10-3.20 (m, 1H), 3.56-3.68 (m, 1H), 6.62 (d, 1H, J = 8.0 Hz), 6.93 (d, 1H, J = 8.0 Hz), 6.98 (t, 1H, J = 4.5 Hz), 7.10-7.15 (m, 3H), 7.43 (d, 2H, J = 8.0 Hz).
化合物Ij-102
1H-NMR (DMSO-d6) δ: 0.92-1.05 (m, 2H), 1.08-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.36-1.43 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.09 (m, 2H), 2.77-2.83 (m, 2H), 3.10-3.20 (m, 1H), 3.57-3.68 (m, 1H), 6.65 (d, 1H, J = 8.0 Hz), 6.94 (d, 1H, J = 8.0 Hz), 6.97 (t, 1H, J = 4.5 Hz), 7.06 (d, 1H, J = 8.0 Hz), 7.13 (d, 1H, J = 8.0 Hz), 7.18-7.26 (m, 2H), 7.41 (t, 1H, J = 8.0 Hz).
化合物Ij-103
1H-NMR (DMSO-d6) δ: 0.88-1.04 (m, 2H), 1.05-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.43 (m, 1H), 1.77-1.82 (m, 2H), 2.00-2.07 (m, 2H), 2.76-2.82 (m, 2H), 3.08-3.20 (m, 1H), 3.52-3.64 (m, 1H), 6.57 (d, 1H, J = 8.0 Hz), 6.92-7.00 (m, 2H), 7.17 (d, 1H, J = 8.0 Hz), 7.23-7.28 (m, 2H), 7.38 (t, 1H, J = 8.0 Hz), 7.56 (d, 1H, J = 8.0 Hz).
化合物Ij-104
1H-NMR (DMSO-d6) δ: 0.96-1.08 (m, 2H), 1.12-1.24 (m, 2H), 1.19 (t, 3H, J = 7.6 Hz), 1.35-1.46 (m, 1H), 1.78-1.86 (m, 2H), 2.04-2.12 (m, 2H), 2.76-2.82 (m, 2H), 2.98 (q, 2H, J = 7.6 Hz), 3.67-3.78 (m, 1H), 6.27 (s, 2H), 6.71 (d, 1H, J = 8.0 Hz), 6.93 (d, 1H, J = 8.0 Hz), 7.02 (brs, 1H), 7.52 (s, 2H), 7.67 (d, 1H, J = 8.0 Hz).
化合物Ij-105
1H-NMR (DMSO-d6) δ: 0.96-1.08 (m, 2H), 1.13-1.25 (m, 2H), 1.19 (t, 3H, J = 7.6 Hz), 1.35-1.46 (m, 1H), 1.78-1.87 (m, 2H), 2.04-2.12 (m, 2H), 2.76-2.83 (m, 2H), 2.99 (q, 2H, J = 7.6 Hz), 3.72-3.82 (m, 1H), 6.82 (d, 1H, J = 8.0 Hz), 6.85 (d, 1H, J = 8.0 Hz), 7.03 (t, 1H, J = 4.5 Hz), 7.12 (t, 1H, J = 4.0 Hz), 7.51 (d, 1H, J = 4.0 Hz), 7.56 (d, 1H, J = 4.0 Hz), 7.76 (d, 1H, J = 8.0 Hz).
化合物Ij-106
1H-NMR (DMSO-d6) δ: 0.88-1.02 (m, 2H), 1.07-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.45 (m, 1H), 1.76-1.85 (m, 2H), 2.02-2.08 (m, 2H), 2.76-2.83 (m, 2H), 3.10-3.20 (m, 1H), 3.57-3.67 (m, 1H), 6.63 (d, 1H, J = 8.0 Hz), 6.92-7.00 (m, 3H), 7.13 (d, 1H, J = 8.0 Hz), 7.29-7.36 (m, 1H), 7.42-7.50 (m, 1H).
化合物Ij-107
1H-NMR (DMSO-d6) δ: 0.88-1.02 (m, 2H), 1.07-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.43 (m, 1H), 1.75-1.83 (m, 2H), 1.98-2.06 (m, 2H), 2.76-2.83 (m, 2H), 3.08-3.18 (m, 1H), 3.52-3.63 (m, 1H), 6.57 (d, 1H, J = 8.0 Hz), 6.93 (d, 1H, J = 8.0 Hz), 6.97 (t, 1H, J = 4.5 Hz), 7.12 (t, 1H, J = 4.0 Hz), 7.19 (d, 1H, J = 8.0 Hz), 7.33-7.47 (m, 2H).
化合物Ij-108
1H-NMR (DMSO-d6) δ: 0.88-1.02 (m, 2H), 1.07-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.33-1.43 (m, 1H), 1.75-1.83 (m, 2H), 1.98-2.07 (m, 2H), 2.76-2.83 (m, 2H), 3.08-3.18 (m, 1H), 3.54-3.63 (m, 1H), 6.63 (d, 1H, J = 8.0 Hz), 6.93-7.00 (m, 2H), 7.14 (t, 1H, J = 8.0 Hz), 7.20-7.37 (m, 3H).
化合物Ij-109
1H-NMR (DMSO-d6) δ: 0.82-1.05 (m, 2H), 1.05-1.20 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.32-1.43 (m, 1H), 1.76-1.83 (m, 2H), 2.00-2.08 (m, 2H), 2.29 (s, 3H), 2.76-2.83 (m, 2H), 3.08-3.18 (m, 1H), 3.56-3.66 (m, 1H), 6.55 (d, 1H, J = 8.0 Hz), 6.90 (d, 1H, J = 8.0 Hz), 6.93-7.00 (m, 3H), 7.05 (d, 1H, J = 8.0 Hz), 7.17 (d, 2H, J = 8.0 Hz).
化合物Ij-110
1H-NMR (DMSO-d6) δ: 0.91-1.19 (m, 4H), 1.28 (s, 9H), 1.32-1.43 (m, 1H), 1.80 (d, 2H, J = 12.0 Hz), 2.07 (d, 2H, J = 12.0 Hz), 2.88 (t, 2H, J = 6.4 Hz), 3.16-3.27 (m, 1H), 5.47 (d, 1H, J = 7.6 Hz), 5.80 (s, 1H), 6.83 (d, 1H, J = 6.0 Hz), 7.15-7.40 (m, 3H), 7.75 (t, 1H, J = 8.4 Hz), 7.86 (s, 1H).
化合物Ij-111
1H-NMR (DMSO-d6) δ: 0.91-1.19 (m, 4H), 1.21 (d, 6H, J = 6.9 Hz), 1.32-1.43 (m, 1H), 1.76-1.82 (m, 2H), 2.02-2.12 (m, 2H), 2.77-2.83 (m, 2H), 3.08-3.27 (m, 2H), 5.48 (d, 1H, J = 8.1 Hz), 5.80 (d, 1H, J = 2.7 Hz), 6.95 (t, 1H, J = 6.0 Hz), 7.15-7.39 (m, 3H), 7.75 (td, 1H, J = 8.4, 1.8 Hz), 7.86 (t, 1H, J = 2.7 Hz).
化合物Ij-112
1H-NMR (DMSO-d6) δ: 0.91-1.19 (m, 4H), 1.18 (t, 3H, J = 7.2 Hz), 1.30-1.45 (m, 1H), 1.76-1.82 (m, 2H), 2.02-2.12 (m, 2H), 2.77-2.83 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz) 3.10-3.30 (m, 1H), 5.48 (d, 1H, J = 7.8 Hz), 5.80 (d, 1H, J = 2.7 Hz), 6.99 (t, 1H, J = 6.0 Hz), 7.15-7.40 (m, 3H), 7.75 (td, 1H, J = 8.4, 1.8 Hz), 7.86 (t, 1H, J = 2.7 Hz).
化合物Ij-113
化合物Ij-114
化合物Ij-115
1H-NMR (DMSO-d6) δ: 0.92-1.19 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.30-1.45 (m, 1H), 1.76-1.84 (m, 2H), 2.02-2.12 (m, 2H), 2.74-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz) 3.15-3.30 (m, 1H), 5.53 (d, 1H, J = 8.1 Hz), 5.80 (d, 1H, J = 2.4 Hz), 6.92 (t, 1H, J = 8.4 Hz), 7.01 (t, 1H, J = 6.0 Hz), 7.37-7.43 (m, 3H), 8.21 (d, 1H, J = 2.4 Hz).
化合物Ij-116
化合物Ij-117
化合物Ij-118
1H-NMR (DMSO-d6)δ: 0.92-1.19 (m, 4H), 1.19 (t, 3H, J = 7.5 Hz), 1.30-1.45 (m, 1H), 1.75-1.86 (m, 2H), 2.02-2.12 (m, 2H), 2.74-2.83 (m, 2H), 2.97 (q, 2H, J = 7.5 Hz) 3.13-3.30 (m, 1H), 5.38 (d, 1H, J = 8.4 Hz), 5.75 (d, 1H, J = 2.7 Hz), 6.99 (t, 1H, J = 6.3 Hz), 7.18-7.28 (m, 2H), 7.63-7.70 (m, 2H), 8.11 (d, 1H, J = 2.7 Hz).
化合物Ij-119
1H-NMR (DMSO-d6) δ: 0.88-1.19 (m, 4H), 1.18 (t, 3H, J = 7.5 Hz), 1.28-1.45 (m, 1H), 1.73-1.83 (m, 2H), 2.02-2.13 (m, 2H), 2.73-2.81 (m, 2H), 2.95 (q, 2H, J = 7.5 Hz) 3.12-3.30 (m, 1H), 5.36 (d, 1H, J = 7.5 Hz), 5.76 (d, 1H, J = 2.4 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.30 (td, 1H, J = 7.5, 1.8 Hz), 7.42 (td, 1H, J = 7.8, 1.5 Hz), 7.53-7.60 (m, 2H), 7.84 (d, 1H, J = 2.7 Hz).
化合物Ij-120
1H-NMR (DMSO-d6) δ: 0.92-1.19 (m, 4H), 1.19 (t, 3H, J = 7.5 Hz), 1.30-1.45 (m, 1H), 1.74-1.84 (m, 2H), 2.02-2.10 (m, 2H), 2.75-2.82 (m, 2H), 2.97 (q, 2H, J = 7.5 Hz) 3.20-3.30 (m, 1H), 5.52 (d, 1H, J = 7.8 Hz), 5.80 (d, 1H, J = 2.4 Hz), 6.99 (t, 1H, J = 6.0 Hz), 7.13 (d, 1H, J = 8.1 Hz), 7.40 (t, 1H, J = 8.1 Hz), 7.62 (d, 1H, J = 8.4 Hz), 7.72 (s, 1H), 8.22 (d, 1H, J = 2.4 Hz).
化合物Ij-121
1H-NMR (DMSO-d6) δ: 0.92-1.19 (m, 4H), 1.19 (t, 3H, J = 7.5 Hz), 1.30-1.45 (m, 1H), 1.74-1.84 (m, 2H), 2.02-2.12 (m, 2H), 2.75-2.82 (m, 2H), 2.98 (q, 2H, J = 7.5 Hz) 3.15-3.30 (m, 1H), 5.47 (d, 1H, J = 8.1 Hz), 5.78 (d, 1H, J = 2.4 Hz), 7.00 (t, 1H, J = 6.0 Hz), 7.43 (d, 2H, J = 7.8 Hz), 7.67 (d, 2H, J = 9.0 Hz), 8.17 (d, 1H, J = 2.4 Hz).
化合物Ij-122
1H-NMR (DMSO-d6) δ: 0.94-1.07 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.32-1.50 (m, 1H), 1.81-1.84 (m, 2H), 1.99-2.07 (m, 2H), 2.77-2.81 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.60-3.77 (m, 1H), 7.01-7.05 (m, 1H), 7.22-7.40 (m, 4H), 7.81-7.87 (m, 1H), 8.02 (s, 1H), 8.36 (s, 1H).
化合物Ij-123
1H-NMR (DMSO-d6) δ: 0.95-1.12 (m, 4H), 1.18 (t, 3H, J = 7.2 Hz), 1.32-1.50 (m, 1H), 1.77-1.81 (m, 2H), 1.96-1.99 (m, 2H), 2.74-2.78 (m, 2H), 2.97 (q, 2H, J = 7.2 Hz), 3.54-3.70 (m, 1H), 4.81 (q, 2H, J = 9.0 Hz), 6.50-6.53 (m, 1H), 6.99-7.03 (m, 1H), 7.50 (d, 1H, J =0.9 Hz) 7.83 (d, 1H, J = 0.9 Hz).
化合物Ij-124
1H-NMR (DMSO-d6) δ: 0.95-1.23 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.32-1.50 (m, 1H), 1.77-1.81 (m, 2H), 2.03-2.07 (m, 2H), 2.74-2.80 (m, 2H), 2.97 (q, 2H, J = 7.2 Hz), 3.61-3.73 (m, 1H), 7.00-7.04 (m, 1H), 7.09-7.12 (m, 1H), 7.29-7.37 (m, 2H), 7.45-7.52 (m, 1H), 7.88-7.94 (m, 2H), 8.04-8.05 (m, 1H).
化合物Ij-125
1H-NMR (DMSO-d6) δ: 0.94-1.14 (m, 4H), 1.19 (t, 3H, J = 7.2 Hz), 1.32-1.50 (m, 1H), 1.79-1.83 (m, 2H), 1.97-2.03 (m, 2H), 2.76-2.81 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.50-3.63 (m, 1H), 4.43 (q, 2H, J = 9.0 Hz), 7.00-7.04 (m, 1H), 7.13-7.15 (m, 1H), 7.35 (s, 1H) 7.55 (s, 1H).
化合物Ij-126
1H-NMR (DMSO-d6) δ: 1.02-1.08 (m, 2H), 1.17-1.29 (m, 2H), 1.19 (t, 3H, J = 7.5 Hz), 1.36-1.43 (m, 1H), 1.79-1.85 (m, 2H), 2.05-2.11 (m, 2H), 2.79 (t, 2H, J = 6.0 Hz), 2.99 (q, 2H, J = 7.5 Hz), 3.53-3.62 (m, 1H), 6.98 (t, 1H, J = 7.8 Hz), 7.03 (t, 1H, J = 6.3 Hz), 7.28 (dd, 1H, J = 7.5, 1.2 Hz), 7.63 (dd, 1H, J = 7.5, 1.2 Hz), 8.28 (d, 1H, J = 7.5 Hz).
化合物Ij-127
1H-NMR (DMSO-d6) δ: 0.97-1.05 (m, 2H), 1.18-1.24 (m, 2H), 1.16 (t, 3H, J = 7.5 Hz), 1.34-1.41 (m, 1H), 1.77-1.81 (m, 2H), 2.02-2.08 (m, 2H), 2.76 (t, 2H, J = 6.0 Hz), 2.96 (q, 2H, J = 7.5 Hz), 3.55-3.64 (m, 1H), 7.00 (t, 1H, J = 7.8 Hz), 7.18 (dd, 1H, J = 8.4, 1.8 Hz), 7.32 (dd, 1H, J = 8.4, 0.6 Hz), 7.74 (d, 1H, J = 1.8 Hz), 8.04 (d, 1H, J = 7.8 Hz).
化合物Ij-128
1H-NMR (DMSO-d6) δ: 0.98-1.07 (m, 2H), 1.15-1.26 (m, 8H), 1.32-1.43 (m, 1H), 1.78-1.84 (m, 2H), 1.98-2.09 (m, 2H), 2.60 (q, 2H, J = 7.5 Hz), 2.78 (t, 2H, J = 6.3 Hz), 2.96 (q, 2H, J = 7.5 Hz), 3.55-3.64 (m, 1H), 6.98-7.05 (m, 2H), 7.27 (dd, 1H, J = 7.8, 1.8 Hz), 7.47 (m, 1H), 7.84 (d, 1H, J =7.5 Hz).
化合物Ij-129
1H-NMR (DMSO-d6) δ: 0.92-1.15 (m, 2H), 1.15-1.35 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.48 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.16 (m, 2H), 2.78-2.84 (m, 2H), 2.97 (q, 2H, J = 7.2 Hz), 3.62-3.80 (m, 1H), 7.02 (t, 1H, J = 6.0 Hz), 7.45 (d, 1H, J = 9.0 Hz), 8.09 (dd, 1H, J = 9.0, 2.4 Hz), 8.68 (d, 1H, J = 2.4 Hz), 8.70 (brs, 1H).
化合物Ij-130
1H-NMR (DMSO-d6) δ: 0.88-1.10 (m, 2H), 1.15-1.46 (m, 3H), 1.21 (d, 6H, J = 6.6 Hz), 1.78-1.88 (m, 2H), 1.98-2.08 (m, 2H), 2.76-2.86 (m, 2H), 3.10-3.20 (m, 1H), 3.46-3.62 (m, 1H), 6.91-6.96 (m, 1H), 7.01 (brs, 1H), 7.64 (d, 1H, J = 7.8 Hz), 8.07 (d, 1H, J = 5.1 Hz), 8.35 (d, 1H, J = 7.8 Hz).
化合物Ij-131
1H-NMR (DMSO-d6) δ: 0.92-1.05 (m, 2H), 1.15-1.30 (m, 2H), 1.27 (s, 9H), 1.30-1.43 (m, 1H), 1.77-1.86 (m, 2H), 1.98-2.08 (m, 2H), 2.86-2.92 (m, 2H), 3.35-3.50 (m, 1H), 3.73 (s, 3H), 6.69 (dd, 1H, J = 8.4, 2.0 Hz), 6.86 (t, 1H, J = 6.0 Hz), 7.01 (d, 1H, J = 2.0 Hz), 7.10 (d, 1H, J = 8.4 Hz), 7.62 (d, 1H, J = 7.6 Hz).
化合物Ij-132
1H-NMR (DMSO-d6)δ: 0.92-1.08 (m, 2H), 1.15-1.33 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.42 (m, 1H), 1.76-1.86 (m, 2H), 1.98-2.08 (m, 2H), 2.76-2.82 (m, 2H), 2.97 (q, 2H, J = 7.2 Hz), 3.40-3.58 (m, 1H), 7.01 (t, 1H, J = 6.0 Hz), 7.13 (d, 1H, J = 8.4 Hz), 7.20 (d, 1H, J = 8.4 Hz), 7.49 (s, 1H), 8.01 (d, 1H, J = 7.6 Hz).
化合物Ij-133
1H-NMR (DMSO-d6) δ: 0.96-1.10 (m, 2H), 1.16-1.28 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.46 (m, 1H), 1.78-1.85 (m, 2H), 2.04-2.12 (m, 2H), 2.76-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.55-3.70 (m, 1H), 7.01 (t, 1H, J = 6.0 Hz), 7.12 (t, 1H, J = 9.6 Hz), 7.48 (d, 1H, J = 7.6 Hz), 8.13 (d, 1H, J = 7.6 Hz).
化合物Ij-134
1H-NMR (DMSO-d6) δ: 0.98-1.08 (m, 2H), 1.15-1.26 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.33-1.42 (m, 1H), 1.39-1.84 (m, 2H), 2.05-2.09 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.10-3.20 (m, 1H), 3.61-3.75 (m, 1H), 6.98 (t, 1H, J = 6.0 Hz), 7.45 (dd, 1H, J = 7.5, 0.6 Hz), 7.60 (dd, 1H, J = 8.4, 1.5 Hz), 8.17 (d, 1H, J = 1.5 Hz), 8.50 (d, 1H, J = 7.5 Hz).
化合物Ij-135
1H-NMR (DMSO-d6) δ: 0.98-1.08 (m, 2H), 1.15-1.25 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.35-1.44 (m, 1H), 1.80-1.84 (m, 2H), 2.05-2.08 (m, 2H), 2.81 (t, 2H, J = 6.3 Hz), 3.10-3.19 (m, 1H), 3.62-3.78 (m, 1H), 6.98 (t, 1H, J = 6.0 Hz), 7.79 (d, 1H, J = 2.1 Hz), 8.10 (d, 1H, J = 2.1, 1.5 Hz), 8.52 (d, 1H, J = 6.9 Hz).
化合物Ij-136
1H-NMR (DMSO-d6) δ: 0.97-1.08 (m, 2H), 1.17-1.24 (m, 2H), 1.19 (t, 3H, J = 7.5 Hz), 1.33-1.41 (m, 1H), 1.78-1.83 (m, 2H), 2.04-2.08 (m, 2H), 2.78 (t, 2H, J = 6.3 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.56-3.67 (m, 1H), 7.00-7.04 (m, 2H), 7.39 (d, 1H, J = 2.1 Hz), 7.66 (dd, 1H, J = 8.4, 1.8 Hz), 8.14 (d, 1H, J = 7.5 Hz).
化合物Ij-137
1H-NMR (DMSO-d6) δ: 0.96-1.10 (m, 2H), 1.12-1.28 (m, 2H), 1.21 (d, 6H, J = 6.9 Hz), 1.31 (t, 3H, J = 6.9 Hz), 1.33-1.46 (m, 1H), 1.76-1.85 (m, 2H), 2.02-2.16 (m, 2H), 2.78-2.84 (m, 2H), 3.10-3.22 (m, 1H), 3.50-3.64 (m, 1H), 3.98 (q, 2H, J = 6.9 Hz), 6.78 (dd, 1H, J = 8.7, 2.7 Hz), 6.98 (t, 1H, J = 6.0 Hz), 7.23-7.27 (m, 2H), 7.68 (d, 1H, J = 7.2 Hz).
化合物Ij-138
1H-NMR (DMSO-d6) δ: 0.94-1.08 (m, 2H), 1.14-1.26 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.45 (m, 1H), 1.77-1.86 (m, 2H), 2.03-2.12 (m, 2H), 2.76-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.52-3.68 (m, 1H), 6.97-7.06 (m, 2H), 7.34 (dd, 1H, J = 8.4, 4.8 Hz), 7.56 (dd, 1H, J = 8.4, 2.4 Hz), 7.91 (d, 1H, J = 7.6 Hz).
化合物Ij-139
1H-NMR (DMSO-d6) δ: 0.96-1.12 (m, 2H), 1.16-1.32 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.32-1.46 (m, 1H), 1.78-1.86 (m, 2H), 2.02-2.16 (m, 2H), 2.78-2.84 (m, 2H), 3.10-3.21 (m, 1H), 3.58-3.76 (m, 1H), 7.00 (t, 1H, J = 6.0 Hz), 8.19-8.23 (m, 2H), 8.52 (d, 1H, J = 6.9 Hz).
化合物Ij-140
1H-NMR (DMSO-d6) δ: 0.96-1.12 (m, 2H), 1.12-1.30 (m, 2H), 1.21 (d, 6H, J = 6.6 Hz), 1.32-1.46 (m, 1H), 1.78-1.86 (m, 2H), 2.02-2.16 (m, 2H), 2.78-2.84 (m, 2H), 3.10-3.20 (m, 1H), 3.58-3.78 (m, 1H), 7.01 (t, 1H, J = 6.0 Hz), 8.08 (dd, 1H, J = 8.4, 2.7 Hz), 8.19 (d, 1H, J = 2.7 Hz), 8.38 (d, 1H, J = 7.2 Hz).
化合物Ij-141
1H-NMR (DMSO-d6) δ: 0.97-1.08 (m, 2H), 1.15-1.22 (m, 5H), 1.34-1.42 (m, 1H), 1.78-1.83 (m, 2H), 2.04-2.08 (m, 2H), 2.78 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.53-3.62 (m, 1H), 3.81 (s, 1H), 7.02 (t, 1H, J = 6.3 Hz), 7.41 (s, 1H), 7.53 (s, 1H), 7.88 (d, 1H, J = 7.5 Hz).
化合物Ij-142
1H-NMR (DMSO-d6) δ: 0.94-1.06 (m, 2H), 1.17-1.30 (m, 2H), 1.18 (t, 3H, J = 7.5 Hz), 1.32-1.41 (m, 1H), 1.79-1.84 (m, 2H), 2.01-2.05 (m, 2H), 2.77 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 7.2 Hz), 3.41-3.58 (m, 1H), 6.97 (dd, 1H, J = 8.4, 2.4 Hz), 6.99-7.03 (m, 1H), 7.27 (d, 1H, J = 2.4 Hz), 7.34 (dd, 1H, J = 8.4, 0.3 Hz), 8.07-8.14 (m, 1H).
化合物Ij-143
1H-NMR (DMSO-d6) δ: 0.94-1.08 (m, 2H), 1.16-1.33 (m, 2H), 1.19 (t, 3H, J = 7.2 Hz), 1.33-1.45 (m, 1H), 1.77-1.86 (m, 2H), 2.00-2.08 (m, 2H), 2.74-2.82 (m, 2H), 2.98 (q, 2H, J = 7.2 Hz), 3.38-3.54 (m, 1H), 6.90-7.00 (m, 1H), 7.02 (t, 1H, J = 4.5 Hz), 7.19 (dd, 1H, J = 8.4, 5.1 Hz), 7.33 (dd, 1H, J = 8.4, 2.7 Hz), 7.88 (d, 1H, J = 7.8 Hz).
化合物Ij-144
1H-NMR (DMSO-d6) δ: 0.94-1.06 (m, 2H), 1.19-1.29 (m, 2H), 1.18 (t, 3H, J = 7.2 Hz), 1.31-1.41 (m, 1H), 1.79-1.84 (m, 2H), 2.01-2.05 (m, 2H), 2.77 (t, 2H, J = 6.0 Hz), 2.98 (q, 2H, J = 6.9 Hz), 3.41-3.57 (m, 1H), 6.71-6.79 (m, 1H), 7.06-7.08 (m, 2H), 7.31 (dd, 1H, J = 8.7, 4.8 Hz), 8.03 (d, 1H, J = 7.8 Hz).
化合物Ij-145
1H-NMR (DMSO-d6) δ: 0.95-1.16 (m, 2H), 1.18-1.44 (m, 3H), 1.21 (d, 6H, J = 6.6 Hz), 1.78-1.86 (m, 2H), 2.02-2.12 (m, 2H), 2.78-2.84 (m, 2H), 3.10-3.20 (m, 1H), 3.40-3.58 (m, 1H), 6.95 (t, 1H, J = 7.8 Hz), 7.01 (brs, 1H), 7.09 (t, 1H, J = 6.9 Hz), 7.22 (d, 1H, J = 6.6 Hz), 7.31 (d, 1H, J = 7.8 Hz), 7.83 (d, 1H, J = 7.8 Hz).
化合物Ij-146
化合物Ij-147
化合物Ij-148
脳移行性(脳/血漿分配係数;Kp)について、マウス(Jcl;C57BL/6J mouse, ♂, 7 weeks)静脈内投与(0.5 mg/2 mL/kg)後の血漿および脳内濃度から評価した。その結果、化合物(I-72)の脳 Kp 値(Kp Cont.)は1.29であり、高い脳移行性を示した。
P-gp を介した薬物間相互作用を in vivo で検討するため、P-gp 阻害剤であるシクロスポリンA 20 mg/kg 共存下での脳Kp値(Kp CSA)を測定し、コントロール群(Kp Cont.)と比較した。化合物(I-72)の Kp CSA は1.14であり、Kp Cont. とのKp ratio(Kp CSA / Kp Cont.)は 0.9と、P-gp を介した薬物間相互作用は認められなかった。
ヒトNPY Y5受容体をコードするcDNA配列(WO96/16542号参照)を、発現ベクター pME18S(Takebe et al. Mol. Cell. Biol. 8, 8957)にクローニングした。得られた発現ベクターを、LipofectAMINE試薬(商標、Gibco BRL社)を用いて、宿主細胞CHOに、使用説明書にしたがってトランスフェクションし、NPY Y5受容体安定発現細胞を得た。
NPY Y5受容体を発現させたCHO細胞から調製した膜標品を、本発明に係る化合物および30,000 cpmの[125I]ペプタイドYY(終濃度60 pM:アマーシャム社製)とともに、アッセイ緩衝液(0.1% 牛血清アルブミンを含む20 mM HEPES-Hanks緩衝液、pH 7.4)中で、25℃、2時間インキュベーションした後、1% ポリエチレンイミン処理したグラスフィルターGF/Cにて濾過した。50 mM Tris-HCl緩衝液、pH 7.4にて洗浄後、ガンマカウンターにてグラスフィルター上の放射活性を求めた。非特異的結合は200 nMペプタイドYY存在下で測定し、特異的ペプタイドYY結合に対する被検化合物の50%阻害濃度(IC50値)を求めた[Inui, A. et al. Endocrinology 131, 2090-2096 (1992) 参照]。結果を表1に示す。
本発明に係る化合物は、NPY Y5受容体に対するペプタイドYY(NPYと同属物質)の結合を阻害した。即ち、本化合物はNPY Y5受容体に対して親和性を示した。
ヒトNPY Y5受容体を発現させたCHO細胞を、2.5mMイソブチルメチルキサンチン(SIGMA社)存在下で37℃、20分間インキュベーションした後、本発明に係る化合物を添加し5分間インキュベーションし、その後50 nMNPYおよび10 μMフォルスコリン(Sigma社)を加えて30分間インキュベーションした。1N HClを添加して反応を停止した後、上清中のcAMP量をEIA kit(Amersham LIFE SIENCE社製)を用いて測定した。フォルスコリン刺激によるcAMP生成に対するNPYの抑制作用を100%とし、このNPY作用に対する本発明に係る化合物の50%阻害濃度(IC50値)を求めた。
Y1発現細胞(human neuroblastoma, SK-N-MC)膜標品およびY2発現細胞(human neuroblastoma, SMS-KAN)膜標品を使用して試験例2と同様の方法で試験を行い、本発明に係る化合物のNPY Y1受容体およびNPY Y2受容体に対する親和性を測定した。その結果により、本発明に係る化合物がNPY Y5受容体選択性を有していることを確認することができた。
エーテル麻酔下、雄性C57BL/6Jマウス(12-14 週齢、25-30g)の外後頭稜から鼻背部まで正中に沿って皮膚を切開し、頭蓋骨上部を露出させた。露出部bregma よりlambdaに向かって約 1 mm後方、正中線から左側に約1mmの位置に電気ドリルを用いて直径約1mmの穴を開けた。麻酔から覚醒後のマウスに0.5%ヒドロキシプロピルメチルセルロース(信越化学株式会社製)水溶液あるいはこの水溶液に懸濁した被検物質を強制経口投与し、投与1時間後、NPY Y5受容体特異的アゴニスト([ cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide:Tocris社製)0.1nmolを先に設けた頭部開口部よりカニューレを用いて注入した。注入2時間後および4時間後にマウスの摂食量を測定し、0.5%ヒドロキシメチルセルロース溶液投与群と被検物質投与群との間の摂餌量の差を調査した。その結果、本発明化合物を6mg/kgの用量で投与した場合、0.5%ヒドロキシプロピルメチルセルロースを投与した場合と比較して摂食量が有意に抑制された。
以下に示す製剤例は例示にすぎないものであり、発明の範囲を何ら限定することを意図するものではない。
製剤例1 錠剤
化合物(I−1) 15mg
デンプン 15mg
乳糖 15mg
結晶性セルロース 19mg
ポリビニルアルコール 3mg
蒸留水 30ml
ステアリン酸カルシウム 3mg
ステアリン酸カルシウム以外の成分を均一に混合し、破砕造粒して乾燥し、適当な大きさの顆粒剤とした。次にステアリン酸カルシウムを添加して圧縮成形して錠剤とした。
化合物(I−2) 10mg
ステアリン酸マグネシウム 10mg
乳糖 80mg
を均一に混合して粉末または細粒状として散剤をつくる。それをカプセル容器に充填してカプセル剤とした。
化合物(I−3) 30g
乳糖 265g
ステアリン酸マグネシウム 5g
よく混合し、圧縮成型した後、粉砕、整粒し、篩別して適当な大きさの顆粒剤とした。
Claims (23)
- 式(I):
Yは−S(O)n−(nは1または2である)または−CO−であり、
R2は水素または置換基を有していてもよい低級アルキルであり、
R1およびR2は一緒になって低級アルキレンを形成してもよく、
R7は水素または置換基を有していてもよい低級アルキルであり、
Xは
置換基を有していてもよい低級アルキレン、
置換基を有していてもよい低級アルケニレン、
置換基を有していてもよい−CO−低級アルキレン、
置換基を有していてもよい−CO−低級アルケニレンまたは
但し、
[式中、R14は置換基を有していてもよいフェニルである]ではない)
であり、
−NR2−X−は
Zは置換基を有していてもよい低級アルキル、置換基を有していてもよい低級アルケニル、置換基を有していてもよいアミノ、置換基を有していてもよい低級アルコキシ、置換基を有していてもよい炭化水素環式基、置換基を有していてもよいヘテロ環式基である、
(但し、Zは3環の縮合へテロ環式基、置換基を有していてもよいチアゾリルまたは置換基を有していてもよいキナゾリニルではない)]
である化合物(但し、Xが
- R1が低級アルキルである、請求項1記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- Yが−S(O)2−である、請求項1記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- Zが置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である、請求項1記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- Zが置換基を有していてもよいヘテロ環式基である、請求項5記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- Zが置換基を有していてもよい低級アルキル、置換基を有していてもよいフェニル、置換基を有していてもよいピリジル、置換基を有していてもよいピラゾリル、置換基を有していてもよいイソオキサゾリル、置換基を有していてもよいオキサジアゾリル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニルまたは置換基を有していてもよい2環の縮合へテロ環である、請求項7または8に記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- p+qが1である、請求項10記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- 式(I):
Yは−S(O)2−であり、
R2は水素または置換基を有していてもよい低級アルキルであり、
R7は水素または置換基を有していてもよい低級アルキルであり、
Xは
Zは置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である]
である化合物(但し、Zが3環の縮合へテロ環式基または置換基を有していてもよいピリミジニルである化合物を除く)、その製薬上許容される塩またはそれらの溶媒和物。 - Zが置換基を有していてもよいフェニル、置換基を有していてもよいインダニル、置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいピラゾリル、置換基を有していてもよいイソオキサゾリル、置換基を有していてもよいオキサジアゾリルまたは置換基を有していてもよい2環の縮合へテロ環である、請求項12記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- Zが置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンゾオキサゾリル、置換基を有していてもよいベンゾピリジル、置換基を有していてもよいベンゾピリダジル、置換基を有していてもよいベンゾイミダゾリル、置換基を有していてもよいチアゾロピリジル、置換基を有していてもよいイソキサゾリノニル、置換基を有していてもよいオキサゾリノニル、置換基を有していてもよいベンズオキサジノニルまたは置換基を有していてもよいベンゾキシアゼピノニルである、請求項12記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- 式(I):
Yは−S(O)2−であり、
R2は水素または置換基を有していてもよい低級アルキルであり、
R7は水素または置換基を有していてもよい低級アルキルであり、
Xは
但し、
[式中、R14は置換基を有していてもよいフェニルである]ではない)
であり、
Zは置換基を有していてもよい炭化水素環式基または置換基を有していてもよいヘテロ環式基である]
である化合物(但し、Zが3環の縮合へテロ環式基、置換基を有していてもよいチアゾリルまたは置換基を有していてもよいキナゾリニルである化合物を除く)、その製薬上許容される塩またはそれらの溶媒和物。 - Zが置換基を有していてもよいフェニル、置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいキノリル、置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンズイミダゾリル、置換基を有していてもよいベンズオキサゾリル、置換基を有していてもよいチアゾロピリジルまたは置換基を有していてもよいオキサゾロピリジルである、請求項15記載の化合物、その製薬上許容される塩またはそれらの溶媒和物。
- 式(I):
Yは−S(O)2−であり、
R2は水素または置換基を有していてもよい低級アルキルであり、
R7は水素または置換基を有していてもよい低級アルキルであり、
Xは
Zは置換基を有していてもよいフェニル、置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいキノリル、置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンズイミダゾリル、置換基を有していてもよいベンズオキサゾリル、置換基を有していてもよいチアゾロピリジルまたは置換基を有していてもよいオキサゾロピリジルである]である化合物、その製薬上許容される塩またはそれらの溶媒和物。 - 請求項1〜17のいずれかに記載の化合物、その製薬上許容される塩またはそれらの溶媒和物を有効成分とする医薬組成物。
- 請求項1〜17のいずれかに記載の化合物、その製薬上許容される塩またはそれらの溶媒和物を有効成分とするNPY Y5受容体拮抗剤。
- 式:
(式中、R15はNH2またはOHであり、
Zは置換基を有していてもよいピリジル、置換基を有していてもよいピリダジニル、置換基を有していてもよいピラジニル、置換基を有していてもよいピリミジニル、置換基を有していてもよいキノリル、置換基を有していてもよいイソキノリル、置換基を有していてもよいベンゾチアゾリル、置換基を有していてもよいベンゾオキサゾリル、置換基を有していてもよいベンゾピリジル、置換基を有していてもよいベンゾピリダジル、置換基を有していてもよいベンズイミダゾリル、置換基を有していてもよいベンズオキサゾリル、置換基を有していてもよいチアゾロピリジル置換基を有していてもよいイソキサゾリノニル、置換基を有していてもよいオキサゾリノニル、置換基を有していてもよいベンズオキサジノニルまたは置換基を有していてもよいベンゾキシアゼピノニルである)で示される化合物、その塩またはそれらの溶媒和物。
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US9139518B2 (en) | 2015-09-22 |
RU2011129383A (ru) | 2013-01-20 |
EP2017261A4 (en) | 2014-04-02 |
US20100267945A1 (en) | 2010-10-21 |
MX2008013511A (es) | 2008-10-28 |
TW200811091A (en) | 2008-03-01 |
CA2650683A1 (en) | 2007-11-08 |
WO2007125952A1 (ja) | 2007-11-08 |
BRPI0710950A2 (pt) | 2012-06-26 |
KR101441146B1 (ko) | 2014-09-17 |
JP2010174038A (ja) | 2010-08-12 |
TWI376367B (en) | 2012-11-11 |
NZ572381A (en) | 2011-01-28 |
US9150507B2 (en) | 2015-10-06 |
NO20084983L (no) | 2009-01-28 |
JP2009221230A (ja) | 2009-10-01 |
AU2007244358A1 (en) | 2007-11-08 |
AU2007244358B2 (en) | 2012-06-14 |
KR20090007571A (ko) | 2009-01-19 |
JP4528901B2 (ja) | 2010-08-25 |
ZA200907457B (en) | 2011-12-28 |
JP5392917B2 (ja) | 2014-01-22 |
EP2017261A1 (en) | 2009-01-21 |
US20100063027A1 (en) | 2010-03-11 |
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