JP2020505457A - 2−アリールスルホンアミド−N−アリールアセトアミド誘導体化Stat3 - Google Patents
2−アリールスルホンアミド−N−アリールアセトアミド誘導体化Stat3 Download PDFInfo
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- JP2020505457A JP2020505457A JP2019560057A JP2019560057A JP2020505457A JP 2020505457 A JP2020505457 A JP 2020505457A JP 2019560057 A JP2019560057 A JP 2019560057A JP 2019560057 A JP2019560057 A JP 2019560057A JP 2020505457 A JP2020505457 A JP 2020505457A
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- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- GBABOYUKABKIAF-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IELIFDKJSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- CILBMBUYJCWATM-PYGJLNRPSA-N vinorelbine ditartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC CILBMBUYJCWATM-PYGJLNRPSA-N 0.000 description 1
- 201000005102 vulva cancer Diseases 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229940053867 xeloda Drugs 0.000 description 1
- 229920001221 xylan Polymers 0.000 description 1
- 150000004823 xylans Chemical class 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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Abstract
Description
[政府の権利]
[関連出願]
ここで、アリールまたはヘテロアリールは、ヒドロキシル、カルボン酸、カルボキシレート、ベンゾヒドロキサム酸、ヒドロキシル置換アルキルのうちの1つ以上で置換されていてもよく、
ならびに、それらの溶媒和物、水和物、または薬学的に許容される塩に関するものである。
式中、R11はアリールまたはヘテロアリールを含むかまたは除外することができ、
ここで、アリールまたはヘテロアリールは、ヒドロキシ、カルボン酸、カルボン酸塩、ベンゾヒドロキサム酸、ニトロソ、アルキルカルボン酸、C1〜C6アルキル、およびハロのうちの1つ以上で置換されていてもよく、
式中、R12は(R)−CH(CH3)であり;
ならびに、それらの溶媒和物、水和物、または薬学的に許容される塩に関する。
およびその塩を含み得る。
式中、R14は5〜7員シクロアルキルまたはヘテロシクロアルキル基を含むかまたは除外することができ、ここでシクロアルキル基は1つまたは複数のハロで置換することができ、
式中、R15は置換アリールを含むかまたは除外することができ、ここで置換はヒドロキシ、カルボキシル酸、およびベンゾヒドロキサム酸のうちの1つ以上である。
式中、R16は(R)−CH(CH3)であり;
式中、Yは、CHおよびNであり、
ならびにそれらの溶媒和物、水和物、または薬学的に許容される塩を含むかまたは除外することができる。
を含むことも除外することもできる。
式中、nは1〜3から選択され、
式中、XはCHおよびNを含むかまたは除外することができ、
式中、R17はCH2および0を含むかまたは除外することができ、
式中、R18は水素およびハロを含むかまたは除外することができ、
式中、R19は水素およびヒドロキシルを含むかまたは除外することができ、
式中、R20は、−OH、NHOH、および−(O−,Na+)であり、
ならびに、それらの溶媒和物、水和物、または薬学的に許容される塩を含むかまたは除外することができる。
式中、W,X,Y,およびZはそれぞれ独立してCHまたはNを含むかまたは除外することができる、
式中、R21は、任意に置換されたアリール、任意に置換されたヘテロアリール、またはヘテロ環と縮合した任意に置換されたアリールを含むかまたは除外することができる、
ここで、置換アリールまたは置換ヘテロアリールまたは複素環と縮合した置換アリールは、ヒドロキシル、カルボン酸、カルボン酸塩、ヒドロキサム酸、アミド、アルキルアミド、ジアルキルアミド、アルコキシアミノ、アルキルカルボン酸、C1−C6アルキル、およびハロのうちの1つ以上で置換されることができ、
式中、nは1〜3から選択されるものであり、
ならびにその溶媒和物、水和物、または薬学的に許容される塩に関するものである。
式中、W,X,Y,Z、およびQはそれぞれ独立してCHまたはNを含むかまたは除外することができ、
ここで、dは0、1、2、3、または4から選択され、
式中、R21は本明細書に記載の通りであり、
式中、R22はハロゲンである。
[定義]
[式I〜VIIIの化合物の投与]
[式I〜VIIIの化合物を用いた治療方法]
[医薬製剤/組成物およびその用途]
[併用療法]
[式I〜VIIIの化合物の代謝産物]
[製造品/キット]
[Stat3阻害剤の合成]
[投与量]
[Stat3阻害剤の投与方法]
[Stat3阻害剤を含む組成物の形態と投与量]
[本発明の選択された化合物の合成]
[一般的に使用されている略語]
1H NMR(300MHz,クロロホルム−d)δ 5.70(d,J=8.4 Hz,1H),4.18(p,J=7.2 Hz,1H),1.47(d,J=7.2 Hz.3H),1.40(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 4.80(q,J=7.3 Hz,1H),2.99(s,3H),1.50(d,J=7.3 Hz.3H),1.40(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 4.97(q,J=7.3 Hz,1H),3.00(s,3H),1.57(d,J=7.3 Hz.3H)
1H NMR(300MHz,クロロホルム−d)δ 5.25−5.09(m,1H),3.02(s,3H),1.69(d,J=7.4 Hz.3H)
MS(ESI)m/z 821[M+H]+
MS(ESI)m/z 641.1743[M+H]+
MS(ESI)m/z 663.1562[M+Na]+
MS(ESI)m/z 715.2265[M+H]+
MS(APCI) m/z 625.1900[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.17(d,J=8.4 Hz,2H),7.30(d,J=8.4 Hz,2H),7.13(d,J=8.1 Hz,2H),7.00(d,J=8.1 Hz,2H),4.93−4.73(m,3H),3.17(s,3H),2.60−2.44(m,1H),2.04−1.66(m,6H),1.54− 1.31(m,4H),1.25(d,J=7.2 Hz.3H)
1H NMR(300MHz,クロロホルム−d)δ 7.70(d,J=8.1 Hz,2H),7.56−7.33(m,5H),7.21−7.14(m,2H),7.14−7.06(m,2H),6.97(d,J=7.8Hz,2H),5.06(s,2H),4.88−4.64(m,3H),3.18(s,3H),2.55−2.41(m,1H),1.94−1.69(m,6H),1.50−1.32(m,4H),1.22(d,J=7.2 Hz.3H)
MS(APCI+)m/z 640.1877[M+H]+
MS(ESI)m/z 641.175 1[M+H]+
MS(APCI) m/z 625.18[M+H]+
MS(ESI)m/z 640.20[M+H]+。HRMS(ESI+)C30H30F5N3O5Sに対する計算値:639.1826,実測値639.1823
1H NMR(300MHz,クロロホルム−d)δ 4.55(dd,J=11.0,4.8 Hz,1H),2.97(s,3H),2.05(dqd,J=14.8,7.5,4.8 Hz,1H),1.70(ddq,J =14.5,11.0,7.2 Hz,1H),1.39(s,9H),1.05(t,J = 7.4 Hz.3H)
1H NMR(300MHz,クロロホルム−d)δ 7.61(br.s,1H),4.71(dd,J=11.0,4.8 Hz,1H),2.95(s,3H),2.10(dtd,J=14.5,7.4,4.8 Hz,1H),1.77(ddq,J = 14.5,11.0,7.4 Hz,1H),1.06(t,J = 7.4 Hz.3H)
MS(ESI)m/z 857.2[M+Na]+
MS(ESI)m/z 653.1752[M−H]−
MS(ESI)m/z 653.1737[M−H]−.HRMS(ESI−)C31H3 1F5N206Sについての計算値:654.1823,実測値654.1811
1H NMR(300MHz,クロロホルム−d)δ 3.75(s,3H),1.47(s,9H),1.38(s,4H)
1H NMR(300MHz,クロロホルム−d)δ 1.84−1.76(m,2H),1.70−1.63(m,2H),1.49(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 1.96(br.s,2H),1.44(s,9H),1.25−1.17(m,2H),0.97−0.89(m,2H)
1H NMR(300MHz,クロロホルム−d)δ 1.61−1.45(m,4H),1.32(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 3 .15(s,3H),1.87(br.s,4H),1.37(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 3 .15(s,3H),1.98(br.s,2H),1.59(br.s,1H),1.41−1.10(m,1H)
1H NMR(300MHz,クロロホルム−d)δ 3.16(s,3H),2.30(br.s,2H),1.91(br.s,1H),1.45(br.s,1H)
MS(ESI)m/z 833.2[M+H]+,m/z 855.2[M+Na]+
MS(ESI)m/z 653.1751[M+H]+
MS(ESI)m/z 757[M+H]+,m/z 779[M+Na]+
MS(ESI)m/z 667.2241[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 6.07(s,1H),1.54(s,6H)1.48(s,9H).
1H NMR(300MHz,クロロホルム−d)δ 3.13(t,J=1.6Hz.3H),1.57(s,6H),1.45(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 3.13(t,J = 1.6 Hz.3H),1.57(s,6H),1.45(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 3.23(t,J = 1.6 Hz.3H),1.72(s,6H)
MS(ESI)m/z 835.25[M+H]+
MS(ESI)m/z 655.1911[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.48−7.22(m,5H),4.70−4.41(m,2H),3.80−3.62(m,2H),3.54(dd,J=5.1,3.9 Hz,1H),1.71(br.s,2H),1.47(s,9H)
MS(ESI)m/z 504[M+Na]+
1H NMR(300MHz,クロロホルム−d) δ 7.38−7.31(m,3H),7.27−7.19(m,2H),4.92(dd,J=7.0,4.3 Hz,1H),4.53(d,J=11.5 Hz,1H),4.42(d,J=11.5 Hz,1H),3.97−3.78(m,2H),3.12(s,3H),1.43(s,9H)
MS(ESI)m/z 462[M+Na]+
1H NMR(300MHz,クロロホルム−d) δ 7.44−7.33(m,3H),7.26−7.11(m,2H),5.28(dd,J=7.5,3.4 Hz,1H),4.60−4.39(m,2H),4 .19−3.91(m,2H),3.13(s,3H)
MS(ESI)m/z 949.2[M+Na]+
HRMS(ESI)m/z 657.1697[M+H]+
MS(ESI)m/z 657.1695[M+H]+
1H NMR(300MHz,クロロホルム−d)δ7.41−7.3 1(m,3H),7.23−7.13(m,2H),5.02(dd,J=6.9,3.6 Hz,1H),4.44(q,J = 11.2 Hz,2H),4.07−3.79(m,2H),3.09(s,3H)
1H NMR(300MHz,クロロホルム−d) δ 7.40−7.3 1(m,3H),7.23−7.14(m,2H),5.26(dd,J=7.4,3.4 Hz,1H),4.54−4.39(m,2H),4.15−3.92(m,2H),3.11(s,3H)
MS(ESI)m/z 821.20[M+H]+
MS(ESI)m/z 731.25[M+H]
MS(ESI)m/z 836.3[M+H]+
HRMS(ESI)m/z 656.1847[M+H]+
HRMS(ESI)m/z 639.1597[M−H]−
1H NMR(300MHz,クロロホルム−d) δ 7.43−7.14(m,10H),4.63(tdd,J=7.2,5.4,3.5 Hz,1H),4.53(s,2H),4.25−3.99(m,2H),3.60(t,J = 6.2 Hz,2H),3.29(dd,J=13.4,3.5 Hz,1H),3.09(t,J =7.2 Hz,2H),2.72(dd,J=13.4,9.7 Hz,1H),2.17−1.92(m,2H)
1H NMR(300MHz,クロロホルム−d) δ 7.40−7.13(m,10H),5.28(t,J = 6.4Hz,1H),4.46(d,J=2.3 Hz,2H),4.33(ddt,J = 9.5,8.0,3.2Hz,1H),4.01(dd,J=9.0,2.9Hz,1H),3.80−3.64(m,3H),3.27(dd,J=13.5,3.4Hz,1H),2.77(dd,J=13.5,9.5Hz,1H),2.42−2 .11(m,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.44−7.25(m,5H),4.55(d,J=1.3 Hz,2H),4.22(dd,J=8.5,5.0 Hz,1H),3.66(t,J = 5.6 Hz,2H),2.31−1.94(m,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.44−7.30(m,5H),4.54(s,2H),4.06−3.94(m,1H),3.66−3.55(m,2H),2.26−2.09(m,1H),1.93(ddtd,J=14.2,9.1,5.1,0.8 Hz,1H),1.50(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.45−7.28(m,5H),6.30(d,J=8.9 Hz,1H),4.52(d,J=14.1 Hz,1H),4.48(d,J=14.1 Hz,1H),4.35(ddd,J=8.9,6.5,4.2 Hz,1H),3.71−3.45(m,2H),2.30−2.12(m,1H),2.04(dddd,J=14.8,6.5,5.0,3.9 Hz,1H),1.35(s,9H)
HRMS(ESI)m/z 693.1651[M+Na]+
HRMS(ESI)m/z 671.1846[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.86−7.74(m,2H),7.65(dd,J =7.5,3.6 Hz,2H),7.47−7.27(m,9H),5.56(d,J=9.7 Hz,1H),4.62(d,J=11.5 Hz,1H),4.55−4.13(m,7H),1.48(s,9H),1.29(d,J=11.5 Hz,2H). MS(ESI)m/z 510.2319[M+Na]+
1H NMR(300MHz,クロロホルム−d)δ 7.40−7.29(m,5H),4.61(d,J=11.6 Hz,1H),4.47(d,J=11.6 Hz,1H),3.97(qd,J=6.3,3.7 Hz,1H),3.30(d,J=3.7 Hz,1H),1.61(br.s,2H),1.48(s,9H),1.32(d,J=6.3 Hz.3H)
1H NMR(300MHz,クロロホルム−d) δ 7.39−7.29(m,3H),7.27−7.21(m,2H),5.81(d,J=10.1 Hz,1H),4.58(d,J=11.5 Hz,1H),4.38(d,J=11.5 Hz,1H),4.20−4.06(m,2H),1.38(d,J =6.2 Hz.3H),1.35(s,9H)
HRMS(ESI)m/z 671.1851[M+H]+
MS(ESI)m/z 671.1831[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 5.43(br.s,1H),4.27(br.s,1H),3.91(dd,J=6.1,3.9 Hz,2H),2.41(br.s,1H),1.50(s,9H),1.47(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.39−7.25(m,10H),3.95(d,J=13.4 Hz,2H),3.72(dおよび重複するm,J = 13.4 Hz.3H),3.46(t,J = 7.6 Hz,1H),2.55(t,J = 5.7 Hz,1H),1.59(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.45−7.28(m,10H),3.81(dd,J=8.0,5.1 Hz,1H),3.70(q,J =13.6 Hz,4H),3.07−2.82(m,2H),1.48(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.40−7.22(m,10H),3.72(d,J=13.5 Hz,2H),3.56(dおよび重複するm,J = 13.5 Hz.3H),2.80(dd,J=12.7,4.9 Hz,1H),2.57(dd,J=12.7,8.4 Hz,1H),1.47(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.59− 7.12(m,1OH),5.71(br.s,1H),4.23(t,J = 5.9 Hz,1H),3.74−3.52(m,4H),2.88(qd,J=13.5,5.9 Hz,2H),1.36(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.47−7.23(m,10H),5.03(t,J = 7.4 Hz,1H),3.99(d,J=13.3 Hz,2H),3.38(d,J=13.3 Hz,2H),2.84(d,J=7.4 Hz,2H),2.59(s,3H),1.36(s,9H)
1H NMR(300MHz,クロロホルム−d) ロトマー1:ロトマー2(1.8:1 ratio) δ 7.48−7.30(m,9H),7.27−7 .18(m,1H),5.34−5.14(m,2H),5.09−4.96(m,1H),4.85(ロトマー 1:d,J=16.1 Hz,1H),4.75(ロトマー 2:d,J=15.5 Hz,1H),4.54(ロトマー 2:d,J=15.5 Hz,1H),4.41(ロトマー 1: d,J=16. 1 Hz,1H),3.93(dd,J=14.8,10.8 Hz,1H),3.64−3.43(m,2H),3.03(ロトマー 1:s,3H),2 .84(ロトマー 2:s,3H),1.35(ロトマー 1:s,9H),1.29(ロトマー 2:s,9H)
HRMS(ESI+)m/z 656.1848[M+H]+
HRMS(ESI+)m/z 656.1849[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.78(d,J=7.5 Hz,2H),7.61(d,J=7.5 Hz,2H),7.47−7.25(m,9H),5.79(d,J=8.2 Hz,1H),5 .16(q,J = 12.2 Hz,2H),4.55(dd,J=8.2,4.5 Hz,1H),4.48−4.29(m,2H),4.24(t,J = 7.1Hz,1H),3.14−2.79(m,2H),1.44(s,9H)
MS(ESI+)m/z 532[M+Na]+1H NMR(300MHz,クロロホルム−d)δ7.44−7.30(m,5H),5.14(q,J = 12.1 Hz,2H),4.38(dt,J = 8.9,4.4 Hz,1H),3.19−2.82(m,2H),1.33(s,9H)
MS(ESI)m/z 683.1497[M−H]−
MS(ESI)m/z 707.1468[M+Na]+
1H NMR(300MHz,クロロホルム−d)δ 4.51(dd,J=8.5,3.2 Hz,1H),3.78−3.56(m,2H),2.42−2.19(m,1H),2.14−1.87(m,3H),1.43(s,9H)
LCMS:純度>98%,MS(ESI)m/z 368[M+Na]+1H NMR(300MHz,クロロホルム−d)δ 4.64(dd,J=8.7,3.6 Hz,1H),3.67(q,J = 7.0,6.5 Hz,2H),2.38(dq,J = 12.7,8.7 Hz,1H),2.28−1.98(m,3H)
1H NMR(300MHz,クロロホルム−d)δ 4.94(dd,J=8.8,3.8 Hz,1H),3.71(ddd,J=7.3,6.5,0.7 Hz,2H),2.58−2.28(m,2H),2.19−2.00(m,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.83(d,J=8.2 Hz,1H),7.48−7.29(m,10H),7.11(d,J=8.0 Hz,2H),6.95(d,J=8.0 Hz,2H),6.72(d,J=8.2 Hz,1H),6.60(s,1H),5.36(s,2H),5.11(d,J=14.3 Hz,1H),4.95−4.74(m,2H),4.53(d,J=14.3 Hz,1H),4.45(t,J = 6.7 Hz,1H),3.83−3.55(m,2H),2.57−2.38(m,1H),2.17−1.64(m,9H),1.52−1.11(m,5H). LCMS:純度98%,MS(ESI)m/z 833[M+H]+
HRMS(ESI)m/z 653.1750[M+H]+
HRMS(ESI)m/z 653.1761[M+H]+
MS(ESI): [M+Na]+ = 590,[2M+Na]+ =1157
MS(ESI): [M+Na]+ = 630,[2M+Na]+ = 1237
1H NMR(300MHz,クロロホルム−d)δ 7.85(d,J=8.6 Hz,1H),7.52−7.14(m,14H),6.23(dd,J=8.6,2.2 Hz,1H),6.18(d,J=2.2 Hz,1H),5.32(s,2H),5.10(s,2H),4.46(t,J = 5.4 Hz,1H),4.33(d,J=5.4 Hz,2H),4 .11(dt,J = 10.5,3.3 Hz,2H),3.55(td,J=11.3,3.3 Hz,2H),2.78(tt,J = 10.5,4.9 Hz,1H),1.97−1.69(m,4H). MS(ESI):[M+H]+=508.2,[2M+Na]+=1037.4
MS(ESI):[M+H]+=835.2,[M+Na]+=857.2,[2M+Na]+=1691.45
HRMS(ESI)m/z 655.1516[M+H]+
HRMS(ESI)m/z 655.1537[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.88(d,J=8.5 Hz,1H),7.57−7.29(m,11H),6.75(dd,J=8.5,2.0 Hz,1H),6.66(br.s,1H),5.34(s,2H),5.19(s,2H),1.55(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.81(d,J=8.4 Hz,1H),7.46−7.30(m,12H),7.03(d,J=8.3 Hz,2H),6.85−6.76(m,2H),5.35(s,2H),5.07(s,2H),4.75(s,2H),1.43(s,9H). MS(ESI): 624,626 [M+Na]+
1H NMR(300MHz,クロロホルム−d)δ 7.81(d,J=8.4 Hz,1H),7.77−7.70(m,1H),7.50(t,J = 1.7 Hz,1H),7.46−7.28(m,12H),7.18(d,J=8.0 Hz,2H),6.92−6.80(m,2H),6.71(dd,J=1.9,0.9 Hz,1H),5.34(s,2H),5.06(s,2H),4.82(s,2H),1.45(d,J=1.1 Hz,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.85(d,J=8.6 Hz,1H),7.75(dd,J=1.5,0.9 Hz,1H),7.56−7.23(m,12H),6.71(dd,J=1.9,0.9 Hz,1H),6.24(dd,J=8.6,2.2 Hz,1H),6.19(d,J=2.2 Hz,1H),5.32(s,2H),5.10(s,2H),4.36(s,2H). MS(ESI+)m/z 490.2 [M+H]+
MS(ESI+)m/z 817.1[M+H]+
HRMS(ESI+)m/z 641.1386[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.43−7.29(m,5H),5.15(s,2H),3.84−3.21(m,4H),3.17−2.78(m,1H),2.20−2.02(m,2H),1.45(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 3.19−2.74(m and overlapping br.s,7H),2.16−1.81(m,2H),1.45(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 3.74−3.61(m,2H),3.60−3.44(m,2H),3.04(p,J = 6.7 Hz,1H),2.20(q,J = 6.9 Hz,2H),1.43(s,9H).
MS(ESI)m/z 424[M+Na]+
MS(ESI)m/z 368[M+Na]+
1H NMR(300MHz,クロロホルム−d)δ 7.81(d,J =8.1 Hz,1H),7.49−7.23(m,10H),7.12(d,J=8.1 Hz,2H),6.96(d,J=8.1 Hz,2H),6.59(dd,J=8.1,1.8 Hz,1H),6.30(d,J=1.8 Hz,1H),5.36(s,2H),4.97(d,J=12.5 Hz,1H),4.86(d,J=12.5 Hz,1H),4.75(d,J=14. 1 Hz,1H),4.62(d,J=14. 1 Hz,1H),3.64−3 .19(m,4H),2.73(p,J=7.2 Hz,1H),2.58−2.38(m,1H),2.02−1.59(m,8H),1.49−1.08(m,4H). MS(ESI)m/z 833[M+H]+
HRMS(ESI)m/z 653.1741[M+H]+
HRMS(ESI)m/z 653.1737[M+H]+
MS(ESI)m/z 374.1[M+Na]+
MS(ESI)m/z 861.35[M+Na]+
MS(ESI)m/z 617.3[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.87(d,J=8.2 Hz,1H),7.48−7.28(m,10H),7.12(d,J=8.0 Hz,2H),6.94(d,J=8.0 Hz,2H),6.78(dd,J=8.2,1.7 Hz,1H),6.67(s,1H),5.37(s,2H),5.15(d,J=12.2 Hz,1H),5.05−4.76(m,3H),4.50(d,J=14.4 Hz,1H),3.99−3.62(m,2H),2.58−2.38(m,1H),1.98−1.11(m,14H).
MS(ESI)m/z 847.3[M+H]+
HRMS(ESI)m/z 667.1902[M+H]+
HRMS(ESI)m/z 667.1903[M+H]+
MS(ESI)m/z 346.1[M+Na]+
MS(ESI)m/z 811.35[M+H]+
MS(ESI)m/z 811.35[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.81(d,J=8.2 Hz,1H),7.47−7.29(m,10H),7.13(d,J=8. 1 Hz,2H),6.99(d,J=8.1 Hz,2H),6.62(dd,J=8.2,1.8 Hz,1H),6.43(s,1H),5.37(s,2H),5.05(d,J=12.4 Hz,1H),4.90−4.76(m,2H),4.72(s,2H),4.15−3.88(m,2H),2.59−2.38(m,1H),1.97(q,J=8.4,7.9 Hz,1H),1.91−1.70(m,5H),1.50−1.15(m,6H). MS(ESI)m/z 819.2[M+H]+
HRMS(ESI)m/z 639.1581[M+H]+
HRMS(ESI)m/z 639.1597[M+H]+
HRMS(ESI)m/z 639.1583[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.12(dd,J=8.8,7.0 Hz,1H),8.04−8.00(m,1H),8.00−7.96(m,1H),7.54−7.37(m,5H),5.43(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.75−7.72(m,1H),7.72−7.68(m,1H),7.48−7.32(m,5H),6.77(t,J=8.6 Hz,1H),5.33(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.77(ddd,J=8.5,1.9,0.8 Hz,1H),7.70(dd,J=12.3,1.9 Hz,1H),7.50−7.34(m,5H),7.32−7.16(m,4H),6.68(t,J=8.5 Hz,1H),5.33(s,2H),4.40(s,2H),2.64−2.36(m,1H),2.03−1.68(m,5H),1.59−1.15(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 7.85(dd,J=12.0,9.8 Hz,2H),7.51−7.33(m,5H),7.20−6.87(m,5H),5.38(s,2H),5.32(d,J=14.3 Hz,1H),4.75(q,J=7.1 Hz,1H),4.20(d,J=14.3 Hz,1H),3.16(s,3H),2.46(s,1H),1.93−1.69(m,6H),1.47−1.30(m,4H),1.23(d,J=7.1Hz.3H)
MS(ESI)m/z 643[M+H]+。HRMS(ESI+)C30H28F6N2O5Sに対する計算値: 642.1623,実測値642.1613
1H NMR(300MHz,クロロホルム−d)δ 7.62(d,J=10.3 Hz,1H),7.51−7.37(m,5H),7.14−6.89(m,6H),5.30(d,J=13.8 Hz,1H),5.06(br.s,1H),4.79−4.60(m,1H),4.20(d,J=13.8 Hz,1H),3.16(s,3H),2.53−2.39(m,1H),1.93−1.69(m,6H),1.47−1.33(m,4H),1.23(d,J=7.1 Hz.3H)
MS(ESI)m/z 658[M+H]+。HRMS(ESI+)C30H29F6N3O5Sに対する計算値:657.1732,実測値657.1716
HRMS(ESI+)m/z 655.1692[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.25(d,J=1.7 Hz,1H),8.10(dd,J=8.4 Hz,J=1.7 Hz,1H),7.90(d,J=8.4 Hz,1H),7.53−7.34(m,5H),5.42(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 8.01(d,2.0 Hz,1H),7.86(dd,J=8.6,2.0 Hz,1H),7.50−7.32(m,5H),7.28(d,J=8.3 Hz,2H),7.22(d,J=8.3 Hz,2H),6.65(d,J=8.6 Hz,1H),5.33(s,2H),5.16(t,J=5.5 Hz,1H),4.43(d,J=5.5 Hz,2H),2.61−2.42(m,1H),1.99−1.70(m,6H),1.52−1.32(m,4H)
HRMS(ESI)m/z 659.1455[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.93(s,1H),7.55−7.33(m,6H),7.08(d,J=8.0 Hz,2H),7.04−6.88(m,3H),5.49(d,J=14.3 Hz,1H),5.04(s,2H),4.74−4.49(m,1H),4.06(d,J=14.3 Hz,1H),3.13(s,3H),2.58−2.39(m,1H),1.95−1.68(m,6H),1.49−1.26(m,4H),1.22(d,J=7.1 Hz.3H)
HRMS(ESI) m/z 674.1532[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.86−7.76(m,2H),7.52−7.32(m,5H),6.65(d,J=9.0 Hz,1H),5.34(s,2H),4.02(br.s,2H),2.20(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 8.09(d,J=8.6 Hz,1H),7.94(dd,J=8.6,2.1 Hz,1H),7.88(d,J=2.1 Hz,1H),7.53−7.33(m,5H),6.48(s,1H),5.36(s,2H),2.29(s,3H),1.56(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.89(s,1H),7.81(d,J=8.2 Hz,1H),7.56−7.33(m,5H),7.10(s,4H),6.99−6.85(m,1H),5.36(s,2H),4.82(d,J=14.7 Hz,1H),4.53(d,J=14.7 Hz,1H),2.58−2.39(m,1H),2.04(s,3H),1.93−1.69(m,5H),1.52−1.07(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 7.88(dd,J=8.5,2.1 Hz,1H),7.82(d,J=2.1 Hz,1H),7.52−7.33(m,5H),7.30(d,J=8.2 Hz,2H),7.22(d,J=8.2 Hz,2H),6.62(d,J=8.5 Hz,1H),5.33(s,2H),4.40(s,2H),4.30(br.s,1H),2.63 −2.43(m,1H),2.19(s,3H),1.97−1.70(m,6H),1.53−1.31(m,4H)
HRMS(ESI+)m/z 639.2027[M+H]+
HRMS(ESI+)m/z 639.1980[M+H]+
MS(ESI+)m/z 643.1[M+H]+
HRMS(ESI+)m/z 659.1408[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.85(d,J=8.2 Hz,1H),7.51−7.35(m,5H),7.17(s,1H),7.12(d,J=7.8 Hz,2H),7.05(d,J=8.2 Hz,1H),6.98(d,J=7.8 Hz,2H),5.40(s,2H),4.84(d,J=14.3 Hz,1H),4.66(d,J=14.3 Hz,1H),4.43(t,J= 6.1 Hz,1H),3.85−3.59(m,2H),2.58−2.40(m,1H),2.00−1.65(m,8H),1.48−1.32(m,6H)
HRMS(ESI)m/z 671.1404[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.86(s,2H),7.56−7.33(m,5H),5.39(s,2H),2.36(s,6H)
1H NMR(300MHz,クロロホルム−d)δ 7.72(s,2H),7.53−7.31(m,5H),5.34(s,2H),2.25(s,6H)
1H NMR(300MHz,クロロホルム−d)δ 7.72(s,2H),7.51−7.33(m,5H),7.24(d,J=8.0 Hz,2H),7 .16(d,J=8.0 Hz,2H),5.35(s,2H),4.34(s,2H),2.59−2.42(m,1H),2.32(s,6H),2.00−1.65(m,6H),1.49−1.25(m,4H)
1H NMR(300MHz,クロロホルム−d)δ 7.81(s,2H),7.55−7.37(m,5H),7.06(d,J=8.1 Hz,2H),6.96(d,J=8.1 Hz,2H),5.38(s,2H),4.80(d,J=13.5 Hz,1H),4.53(d,J=13.5 Hz,1H),4.46(q,J=7.0 Hz,1H),3.09(s,3H),2.55−2.37(m,1H),1.96(s,3H),1.91(s,3H),1.88−1.69(m,5H),1.48−1.21(m,5H),1.09(d,J=7.0 Hz.3H)
HRMS(ESI+)m/z 653.2095[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.19−7.14(m,2H),4.29(br.s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.66−7.58(m,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.62−7.55(m,2H),7.49−7.32(m,5H),5.34(s,2H),4.16(br.s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.59−7.50(m,2H),7.48−7.31(m,5H),7.27(d,J=8.1 Hz,2H),7.20(d,J=8.1 Hz,2H),5.33(s,2H),4.59(s,2H),2.65−2.41(m,1H),2.00−1.59(m,6H),1.54−1.12(m,6H)
HRMS(ESI+)m/z 751.2072[M+H]+
HRMS(ESI+)m/z 661.1610[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.44−7.32(m,5H),5.23(s,2H),4.67(dd,J=9.2,5.5 Hz,1H),4.06(ddd,J=8.9,8.0,6.2 Hz,1H),3.91(ddd,J= 8.9,8.0,5.5 Hz,1H),2.52(dtd,J=11.2,9.2,6.2 Hz,1H),2.18(ddt,J=11.2,8.9,5.5 Hz,1H),1.40(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 10.48(br.s,1H),7.46−7.31(m,5H),5.83(br.s,3H),5.35−5.19(m,2H),5.13(dd,J=10.2,7.7 Hz,1H),4.26(td,J=9.8,7.7 Hz,1H),4.10(td,J=10.2,665 Hz,1H),2.95(dtd,J=12.4,9.7,6.6 Hz,1H),2.65(ddt,J=12.4,9.8,7.6 Hz,1H)
MS(ESI)m/z 444.0[M+Na]+1H NMR(300MHz,クロロホルム−d)δ 7.42−7.31(m,3H),7.27−7.18(m,2H),5.21−5.00(m,3H),4.36(dt,J=9.4,7.4 Hz,1H),4.05(td,J=8.0,4.9 Hz,1H),2.65(dtd,J=11.4,9.4,4.9 Hz,1H),2.46(ddt,J=11.5,9.1,7.4 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 5.05(dd,J=9.8,7.1 Hz,1H),4.50−3.92(m,2H),2.66(dtd,J=11.5,9.4,4.9 Hz,1H),2.49(ddt,J=11.5,9.0,7.3 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 5.26(dd,J=10.0,7.1 Hz,1H),4.33(dt,J=9.2,7.3 Hz,1H),4.02(ddd,J=9.1,7.4,4.9 Hz,1H),2.79(dddd,J=11.7,10.0,9.0,4.9 Hz,1H),2.56(ddt,J=11.6,9.1,7.1 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 7.77(ddd,J=8.5,1.9,0.8 Hz,1H),7.70(dd,J=12.3,1.9 Hz,1H),7.50−7.33(m,5H),7.31−7.16(m,4H),6.68(t,J=8.5 Hz,1H),5.33(s,2H),4.40(s,2H),2.63−2.40(m,1H),2.04−1.69(m,5H),1.60−1.13(m,5H)
MS(ESI)m/z 731.2032[M+H]+
MS(ESI)m/z 641.1550[M+H]+
MS(ESI)m/z 656.1655[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.59(d,J=8.8 Hz,2H),7.50(d,J=8.8 Hz,2H),6.71(brs,1H),1.55(s,9H)
1H NMR(300MHz,クロロホルム−d)δ d 7.67(d,J=8.1 Hz,2H),7.41(s,1H),7.25−7.04(m,6H),4.82(s,2H),2.59 −2.42(m,1H),1.97− 1.70(m,6H),1.59(s,9H),1.51−1.30(m,4H)
1H NMR(300MHz,クロロホルム−d)δ 8.05(d,J=8.7 Hz,2H),7.50−7.34(m,5H),7.28(d,J=8.7 Hz,2H),7.15(m,4H),5.81(s,2H),4.85(s,2H),2.56−2.41(m,1H),1.96−1.69(m,6H),1.45(s および重複するm,13H)
1H NMR(300MHz,クロロホルム−d)δ 7.96(d,J=8.8 Hz,2H),7.39(m,5H),4.36(s,2H),2.63−2.42(m,1H),2.02−1.66(m,6H),1.58−1.16(m,4H)
1H NMR(300MHz,クロロホルム−d)δ 8.12(d,J=8.6 Hz,2H),7.49−7.35(m,5H),7.16−6.96(m,6H),5.83(s,2H),5.01−4.91(m,lH),4.87(d,J=14.3 Hz,1H),4.72(d,J=14.3 Hz,1H),4.26(t,J=8.2 Hz,1H),4.09−3.85(m,1H),2.56−2.40(m,1H),2.33−2.15(m,1H),1.98−1.69(m,6H),1.39(t,J=10.1 Hz,4H)
HRMS(ESI+)m/z 647.1866[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 9.20(d,J=2.2 Hz,1H),8.32(d,J=8.2 Hz,1H),7.5 1(d,J=8.2 Hz,1H),7.03(br s,1H),3.97(s,3H),2.62−2.48(m,2H),2.42−2.27(m,2H),1.92−1.78(m,2H),1.77−1.66(m,2H)
1H NMR(300MHz,クロロホルム−d)δ 9.15(d,J=2.2,1H),8.25(dd,J =8.2,2.2 Hz,1H),7.28(d,J=8.2,1H),3.96(s,3H),2.83(tt,J=11.7,3.4 Hz,1H),2.10−1.70(m,5H),1.68−1.18(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 8.56−8.49(m,1H),7.67(dd,J=8.0,2.3 Hz,1H),7.18(d,=8.0 Hz,1H),4.7 1(s,2H),2.73(tt,J=11.7,3.4 Hz,1H),2.04−1. 15(m,10H)
1H NMR(300MHz,クロロホルム−d)δ 8.55(d,J=2.4 Hz,1H),7.67(dd,J=8.1,2.4 Hz,1H),7.17(d,J=8.1 Hz,1H),4.49(s,2H),2.72(tt,J=11.6,3.4 Hz,1H),2.08−1.71(m,5H),1.58−1.21(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 8.26(d,J=2.3 Hz,1H),7.85(d,J=8.3 Hz,1H),7.52−7.44(m,1H),7.43−7.32(m,10H),7.12(d,J=8.0 Hz,1H),6.74−6.64(m,1H),6.57(s,1H),5.36(s,2H),4.98(s,2H),4.84(s,2H),2.77−2.61(m,1H),2.02−1.69(m,6H),1.54−1.32(m,4H)
1H NMR(300MHz,クロロホルム−d)δ 8.53(d,J=2.1Hz,1H),7.85(d,J=8.6 Hz,1H),7.58(dd,J=8.1,2.4 Hz,1H),7.15(d,J=8.1 Hz,1H),6.23(dd,J=8.6,2.2 Hz,1H),6.18(d,J=2.2 Hz,1H),5.32(s,2H),5.11(s,2H),4.43(br s,1H),4.33(s,2H),2.86−2.62(m,1H),2.08−1.69(m,6H),1.66−1.18(m,4H)
MS(ESI+)m/z 820.3[M+H]+
MS(ESI+)m/z 640.2[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.56(d,J=2.5 Hz,1H),7.85(dd,J=8.2,1.0 Hz,1H),7.78(dd,J=8.3,2.4 Hz,1H),7.52−7.3 1(m,10H),7.17(d,J=8.6 Hz,1H),6.96(d,J=1.7 Hz,1H),6.88(d,J=8.4 Hz,1H),5.35(s,2H),5.10(s,2H),4.93(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 8.65(d,J =2.3 Hz,1H),7.93−7.81(m,1H),7.77(dd,J=8.3,2.3 Hz,1H),7.53−7.29(m,10H),7.21−7.13(m,1H),6.25(dd,J=8.5,2.2 Hz,1H),6.20(d,J=2.2 Hz,1H),5.32(s,2H),5.26−5.17(m,1H),5.13(s,2H),4.44(d,J=4.9 Hz,2H)
1H NMR(300MHz,クロロホルム−d)δ 8.54(s,1H),7.83(d,J=8.2 Hz,1H),7.76(d,J=8.5 Hz,1H),7.51−7.32(m,10H),7.13(d,J=8.3 Hz,1H),6.88(s,1H),6.79(d,J=8.2 Hz,1H),5.38(s,2H),5.26−5.06(m,2H),5.00−4.89(m,1H),4.83(s,2H),4.10−3.86(m,2H),2.18−1.97(m,1H),1.85−1.67(m,1H)
MS(ESI+)m/z 818.2[M+H]+
HRMS(ESI)m/z 640.1538[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.48−7.32(m,5H),5.19(s,2H),4.21 −4.00(m,4H),3.50 −3.30(m,1H),1.45(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.44−7.3 1(m,5H),5.22(s,2H),4.47−4.18(m,4H),3.81(td,J=8.9,7.5 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 7.44−7.30(m,5H),5.15(s,2H),4.43−4.11(m,4H),3.47(tt,J=9.0,6.4 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 4.32(dt,J=24.9,8.2 Hz,4H),3.64−3.39(m,1H)
1H NMR(300MHz,クロロホルム−d)δ 4.37(h,J=8.0,7.3 Hz,4H),3.88(tt,J= 9.1,6.4 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 7.82(d,J=8.1 Hz,1H),7.53−7.32(m,10H),7.15(D,J=7.8 Hz,2H),6.98(d,J=7.8 Hz,2H),6.60−6.45(m,1H),6.23(s,1H),5.38(s,2H),4.93(s,2H),4.72(s,2H),4.03(t,J=7.5 Hz,2H),3.63(t,J=8.4 Hz,2H),3.05(q,J=7.5 Hz,1H),2.60−2.41(m,1H),1.97− 1.70(m,5H),1.52−1.14(m,5H)
HRMS(ESI)m/z 639.1591[M+H]+
LCMS(ESI+)m/z 729.10[M+H]+
MS(ESI)m/z 834.20[M+H]+
HRMS(ESI)m/z 654.1697[M+H]+
MS(ESI)m/z 825.30[M+H]+
MS(ESI)m/z 743.20[M+H]+
MS(ESI)m/z 848.30[M+H]+
MS(ESI)m/z 668.1828[M HRMS(ESI+)C31H30F5N3O6Sの計算値:667.1775,実測値667.1768
1H NMR(300MHz,クロロホルム−d)δ 7.80(d,J=8.4 Hz,1H),7.45−7.29(m,12H),7.15(d,J=8.1 Hz,2H),6.87(d,J=1.9 Hz,1H),6.82(dd,J=8.4,1.9 Hz,1H),6.14(s,1H),5.34(s,2H),5.04(s,2H),4.81(s,2H),4.34(dd,J=5.5 Hz,J= 2.8 Hz,2H),3.95(t,J=5.6 Hz,2H),2.53(t,J=5.6 Hz,2H),1.44(s,9H). MS(ESI):628 [M+Na]+
1H NMR(300MHz,クロロホルム−d)δ 7.85(d,J=8.6 Hz,1H),7.49−7.29(m,14H),6.23(dd,J=8.6,2.2 Hz,1H),6.18(d,J=2.2 Hz,1H),6.15(br.s,1H),5.32(s,2H),5.10(s,2H),4.35(d,J=2.5 Hz,2H),3.96(t,J=5.3 Hz,2H),2.54(dq,J=5.3,2.9 Hz,2H)
HRMS(ESI)m/z 821.2239[M+H]+
HRMS(ESI)m/z 643.1563[M+H]+
MS(ESI)m/z 677.1[M+H]+
MS(ESI)m/z 643.1580[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.80−7.66(m,2H),7.55−7.31(m,7H),7.24(d,J=8.4 Hz,2H),6.63(t,J=8.4 Hz,1H),5.32(s,2H),4.41(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.80−7.64(m,2H),7.51−7.29(m,9H),6.69(t,J=8.3 Hz,1H),6 .19−6.07(m,1H),5.32(s,2H),4.44(s,2H),4.34(q,J=2.8 Hz,2H),3.95(t,J=5.5 Hz,2H),2.62−2.44(m,2H)
MS(ESI):745.2[M+H]+
MS(ESI):657.1[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.92−7.72(m,1H),7.52−7.29(m,10H),6.40−6.26(m,2H),5.33(s,2H),5.14(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.65(d,J=11.8 Hz,1H),7.54−7.30(m,10H),6.36(d,J=7.3 Hz,1H),5.32(s,2H),5.11(s,2H),4.11(br.s,2H)
1H NMR(300MHz,クロロホルム−d)δ 8.20(d,J=6.3 Hz,1H),8.17(br.s,1H),7.74(d,J=11.1 Hz,1H),7.53−7.31(m,10H),5.36(s,2H),5.20(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.66(d,J=9.7 Hz,1H),7.47−7.29(m,10H),7.14(d,J=7.8 Hz,2H),7.06(d,J=7.8 Hz,2H),6.33(d,J=5.9 Hz,1H),5.48(d,J=14.0 Hz,1H),5.35(s,2H),4.85−4.63(m,2H),4.20(d,J=14.0 Hz,1H),2.56−2.41(m,1H),1.94−1.67(m,6H),1.50−1.25(m,4H)
MS(ESI): 837.2[M+H]+
MS(ESI)m/z 657.1486[M+H]+
MS(ESI)m/z 679. 1288[M+Na]+
MS(ESI)m/z 617.1183[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.65(d,J=9.6 Hz,1H),7.51−7.28(m,12H),7.00(d,J=8.2 Hz,2H),6.44(d,J=5.9 Hz,1H),5.36(s,2H),5.24(d,J=14.2 Hz,1H),4.91(q,J=12.1 Hz,2H),4.36(d,J=14.2 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 7.64(d,J=12.4 Hz,1H),7.48(d,J=8.4 Hz,2H),7.44−7.29(m,10H),7.17(d,J=8.4 Hz,2H),6.13(d,J=7.2 Hz,1H),5.32(s,2H),5.02(s,2H),4.77(s,1H),4.33(s,2H)
MS(ESI)m/z 833.00,835.00[M+H]+
MS(ESI)m/z 837.6[M+H]+
MS(ESI)m/z 659.1254[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.38(dd,J=8.3,2.1 Hz,1H),8.30−8.23(m,1H),8.09−7.98(m,1H),7.28(d,J=8.7 Hz,2H),6.90(d,J=8.7 Hz,2H),4.79(s,2H),4.38(s,2H),3.82(s,3H)
MS(ESI)m/z 269[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.78(d,J=8.2 Hz,1H),7.74(br.s,1H),7.23(d,J=8.9 Hz,2H),7.18(dd,J=8.2 Hz,J=1.7 Hz,1H),6.87(d,J=8.9 Hz,2H),6.77(s,1H),4.73(s,2H),4.21(s,2H),3.80(s,3H),1.53(s,9H)
MS(ESI)m/z 541.3[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.67(d,J=8.2 Hz,1H),7.27−7.18(m,4H),6.91−6.80(m,2H),6.73−6.63(dd,J=8.2 Hz,J = 2 .1 Hz,1H),6.53(d,J=2 .1 Hz,1H),4.69(s,2H),4.41(t,J=5.5 Hz,1H),4.33(d,J=4.5 Hz,2H),3.80(s,3H),2.62−2.39(m,1H),2.01−1.70(m,5H),1.52−1.15(m,5H). MS(ESI)m/z 441.2[M+H]+
MS(ESI)m/z 756.2[M+H]+
MS(ESI)m/z 636.1[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.74(d,J=2.1 Hz,1H),8.27−8.19(m,2H),7.41(d,J=9.3 Hz,1H),7.20(d,J=9.3 Hz,2H),6.86(d,J=8.7 Hz,2H),5.59(s,2H),3.79(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 7.83(s,1H),7.22−7.09(m,3H),6.97−6.91(m,1H),6.88−6.75(m,3H),5.48(s,2H),3.78(s,3H),3.60(br.s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.96(d,J=0.8 Hz,1H),7.83(s,1H),7.26−7.19(m,2H),7.14(d,J=8.6 Hz,2H),6.83(d,J=8.6 Hz,2H),6.51(s,1H),5.52(s,2H),3.78(s,3H),1.54(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.94(t,J=0.6 Hz,1H),7.44(s,1H),7.21−7.08(m,8H),6.84(d,J=8.7 Hz,2H),5.50(s,2H),4.81(s,2H),3.78(s,3H),2.59−2.40(m,1H),1.99−1.68(m,5H),1.52−1.34(mおよび重複s,14H)
1H NMR(300MHz,クロロホルム−d)δ 7.84(d,J=0.7 Hz,1H),7.37−7.30(m,2H),7.24−7.12(m,5H),6.88−6.76(m,4H),5.48(s,2H),4.31(s,2H),3.78(s,3H),2.67−2.39(m,1H),2.11−1.67(m,5H),1.52−1.08(m,5H)
MS(ESI)m/z 741.2[M+H]+
MS(ESI)m/z 621.2[M+H]+
MS(ESI)m/z 621.2[M+H]+
HRMS(ESI)m/z 592.1910[M+H]+
HRMS(ESI)m/z 574.2015[M+H]+
HRMS(ESI)m/z 574.2007[M+H]+
MS(ESI)m/z 574.2004[M+H]+
実施例72−75
MS(ESI)m/z 797.2[M+H]+
HRMS(ESI)m/z 617.1923[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.83(d,J=8.2 Hz,1H),7.49−7.28(m,10H),7.14(d,J=8.1 Hz,2H),7.08−7.02(m,2H),6.72(dd,J=8.2,1.8 Hz,1H),6.57(s,1H),5.36(s,2H),5.09(d,J=12.2 Hz,1H),4.97(d,J=14.2 Hz,1H),4.83(d,J=12.2 Hz,1H),4.68(d,J=14.2 Hz,1H),3 .87(t,J=8.0 Hz,1H),3.16(dt,J=11.0,6.8 Hz,1H),2.94(dt,J=11.0,6.8 Hz,1H),2.60−2.32(m,1H),1.94−1.56(m,8H),1.54−1.14(m,6H). MS(ESI)m/z 603.3 [M+H]+
MS(ESI)m/z 797.2[M+H]+
HRMS(ESI)m/z 617.1918[M+H]+
MS(ESI)m/z 797.2[M+H]+
HRMS(ESI)m/z 617.2071[M+H]+
MS(ESI)m/z 783.3[M+H]+
HRMS(ESI)m/z 603.2285[M+H]+
HRMS(ESI)m/z 564.1760[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.85(d,J=8.6 Hz,1H),7.50−7.27(m,12H),7.22(d,J=8.2 Hz,2H),6.24(dd,J=8.6,2.2 Hz,1H),6.19(d,J=2.2 Hz,1H),5.32(s,2H),5.10(s,2H),4.33(s,2H),4.20−3.95(m,2H),3.55(td,J=11.3,3.4 Hz,2H),2.78(tt,J=10.9,4.9 Hz,1H),1.98−1.68(m,4H)
1H NMR(300MHz,クロロホルム−d)δ 7.80(d,J=8.2,1H),7.47−7.31(m,10H),7.14(d,J=8.1 Hz,2H),7.03(d,J=8.1 Hz,2H),6.61(dd,J=8.2,1.8 Hz,1H),6.50(s,1H),5.37(s,2H),5.08(d,J=12.3 Hz,1H),4.91(d,J=12.3 Hz,1H),4.86−4.76(m,2H),4.67(d,J=14.3 Hz,1H),4.15−3.92(m,5H),3.53(td,J=11.3,3.2 Hz,2H),2.84−2.64(m,1H),2.09−1.92(m,1H),1.89−1.64(m,4H)
HRMS(ESI)m/z 641.1382[M+H]+
HRMS(ESI)m/z 663.1196[M+Na]+
HRMS(ESI)m/z 681.1108 [M+Na]+
1H NMR(300MHz,クロロホルム−d)δ 7.84(d,J=8.6,1H),7.47(d,J=8.3 Hz,2H),7.44−7.30(m,10H),7.19(d,J=8.3 Hz,2H),6.21(dd,J=8.6,2.2 Hz,1H),6 .14(d,J=2.2 Hz,1H),5.32(s,2H),5.09(s,2H),4.49(br.s,1H),4.32(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 7.84(d,J=8.6 Hz,1H),7.53−7.23(m,14H),6.30−6.12(m,3H),5.32(s,2H),5.10(s,2H),4.45(s,1H),4.33(d,J=4.2 Hz,2H),2.82−2.63(m,2H),2.54(d,J=8.3 Hz,2H),2.04(p,J= 7.6 Hz,2H)
MS(ESI)m/z 817.10[M+H]+
MS(ESI)m/z 639.1584[M+H]+
HRMS(ESI)m/z 625.1432[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.00(d,J=8.7 Hz,2H),7.82(dd,J=1.5,0.9 Hz,1H),7.59−7.47(m,3H),6.75(dd,J=1.9,0.9 Hz,1H),1.62(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.94(d,J=8.3 Hz,2H),7.31(d,J=8.3 Hz,2H),4.20−4.03(m,2H),3.93(dt,J=8.4,7.5 Hz,1H),3.76(dd,J=8.5,7.1 Hz,1H),3.46(p,J=7.6 Hz,1H),2.48−2.32(m,1H),2.01(dq,J=12.4,7.9 Hz,1H),1.60(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 8.07(d,J=8.3 Hz,2H),7.38(d,J=8.3 Hz,2H),4.25−4.07(m,2H),3.97(dt,J=8.6,7.6 Hz,1H),3.81(dd,J=8.6,7.1 Hz,1H),3.51(p,J=7.6 Hz,1H),2.53−2.34(m,1H),2.05(dq,J=12.4,7.9 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 7.34(d,J=8.2 Hz,2H),7.27(d,J=8.2 Hz,2H),4.68(s,2H),4.22−4.02(m,2H),3.93(td,J=8.2,7.3 Hz,1H),3.73(dd,J=8.2,7.5 Hz,1H),3.42(p,J=7.7 Hz,1H),2.38(dtd,J=12.3,7.7,4.5 Hz,1H),2.11−1.94(m,1H)
1H NMR(300MHz,クロロホルム−d)δ 7.36(d,J=8.2 Hz,2H),7.25(d,J=8.2 Hz,2H),4.50(s,2H),4.19−4.02(m,2H),3.93(dt,J=8.4,7.5 Hz,1H),3.73(dd,J=8.4,7.5 Hz,1H),3.42(p,J=7.7 Hz,1H),2.45−2.31(m,1H),2.01(dq,J=12.3,8.0 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 7.82(d,J=8.3 Hz,1H),7.44−7.31(m,10H),7 .18(d,J=8.2 Hz,2H),7.08(d,J=8.2 Hz,2H),6.68(d,J=8.3 Hz,1H),6.58(s,1H),5.35(s,2H),4.96(s,2H),4.84(s,2H),4.19−4.00(m,2H),3.98−3.83(m,1H),3.77−3.64(m,1H),3.39(p,J=7.7 Hz,1H),2.43−2.27(m,1H),1.96(dq,J=12.3,8.1 Hz,1H)
HRMS(ESI)m/z 807.2179[M+H]+
HRMS(ESI)m/z 627. 1223[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.06(d,J=7.9,2H),7.52−7.35(m,5H),7.05(m,6H),5.39(s,2H),5.00−4.80(m,2H),4.72(d,J=14.4 Hz,1H),4.25−3.89(m,2H),2.62−2.40(m,1H),2.26(dq,J=17.0,8.7,8.0 Hz,1H),2.03−1.71(m,6H),1.68−1.30(m,5H)
HRMS(ESI)m/z 623.1640[M+H]+
HRMS(ESI)m/z 638. 1747[M+H]+
実施例84−85
LCMS(ESI)m/z 731.10[M+H]+
MS(ESI)m/z 836.20[M+H]+
MS(ESI)m/z 656.1493[M+H]+
LCMS(ESI)m/z 819.3[M+H]+
LCMS(ESI)m/z 729.20[M+H]+
MS(ESI)m/z 834.30[M+H]+
HRMS(ESI)m/z 654.1696[M+H]+
実施例86−87
1H NMR(300MHz,クロロホルム−d)δ 8.01(d,J=8.9 Hz,2H),7.50−7.33(m,7H),7.24(d,J=8.7 Hz,2H),7.10(d,J=8.3 Hz,2H),5.36(s,2H),4.84(s,2H),1.44(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.92(d,J=8.8 Hz,2H),7.54−7.32(m,7H),7.23(d,J=8.4 Hz,2H),6.58(d,J=8.8 Hz,2H),5.33(s,2H),4.54(s,1H),4.38(s,2H)
1H NMR(300MHz,クロロホルム−d)δ 8.08(d,J=8.2 Hz,2H),7.54−7.34(m,7H),7.04(d,J=8.4 Hz,2H),6.99(d,J=8.3 Hz,2H),5.39(s,2H),4.97−4.80(m,2H),4.70(d,J=14.4 Hz,1H),4.31−3.84(m,2H),2.32−2.13(m,1H),2.02−1.84(m,1H)
1H NMR(300MHz,クロロホルム−d)δ 8.07(d,J=8.5 Hz,2H),7.53−7.35(m,5H),7.31(d,J=8.2,2H),7.11−7.00(2 overlapping doublets,4H),6.14(q,J=1.5 Hz,1H),5.39(s,2H),4.99−4.84(m,2H),4.72(d,J=14.4 Hz,1H),4.39−4.28(m,2H),4.21−4.01(m,2H),3.94(t,J=5.5 Hz,2H),2.51(m,2H),2.25(dt,J=16.7,7.7 Hz,1H),2.02−1.83(m,1H)
HRMS(ESI)m/z 625.1433[M+H]+。
MS(ESI)m/z 730.10[M+H]+
HRMS(ESI)m/z 640.1540[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.06(d,J=8.3 Hz,2H),7.57−7.30(m,7H),7.14−6.93(m,4H),6.30−6.10(m,1H),5.38(s,2H),4.97−4.81(m,2H),4.75(d,J=14.4 Hz,1H),4.25−3.98(m,2H),2.80−2.64(m,2H),2.62−2.45(m,2H),2.38−2.15(m,1H),2.04−1.80(m,3H)
HRMS(ESI)m/z 609.1486[M+H]+
HRMS(ESI)m/z 624.1589[M+H]+
HRMS(ESI)m/z 674.1398[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.27−7.21(m,4H),4.32(s,2H),2.64−2.42(m,1H),2.00−1.69(m,5H),1.54−1.16(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 7.28−7.14(m,4H),3.85(s,2H),2.62−2.41(m,1H),1.99−1.66(m,6H),1.52−1.16(m,4H)
1H NMR(300MHz,クロロホルム−d)δ 7.76(s,1H),7.27(d,J=8.2 Hz,2H),7.21(d,J=8.2 Hz,2H),5.13−4.94(m,1H),4.55(d,J=5.8 Hz,2H),4.37(q,J=7.1Hz,2H),2.60−2.38(m,1H),1.97−1.70(m,6H),1.51−1.10(m および重複する t,J=7.1 Hz,7H)
1H NMR(300MHz,クロロホルム−d)δ 8.42(br s,1H),7.64(s,1H),7.42−6.96(m,4H),4.51(s,2H),2.62−2.42(m,1H),2.02−1.58(m,5H),1.56−1.08(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 7.76(s,1H),7.49−7.31(m,5H),7.32−7.12(m,4H),5.35(s,2H),5.13(t,J=6.1 Hz,1H),4.54(d,J=5.9 Hz,2H),2.63−2.40(m,1H),1.96−1.60(m,6H),1.51−1.19(m,4H)
HRMS(ESI)m/z 614.1375[M+H]+
MS(ESI)m/z 599.1,601.1[M+H]+
MS(ESI)m/z 525.1,527.1[M+Na]+
MS(ESI)m/z 507.3[M+H]+
MS(ESI)m/z 820.3[M+H]+
HRMS(ESI)m/z 642.1326 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 10.99(s,1H),8.04(d,J=8.7 Hz,1H),7 .84(d,J=2.3 Hz,1H),7.72(dd,J=8.7,2.3 Hz,1H),4.04(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 7.98−7.91(m,1H),7.91−7.82(m,2H),7.57−7.3 1(m,5H),5.30(s,2H),3.96(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 7.82−7.76(m,1H),7.57−7.49(m,2H),7.46−7.29(m,3H),6.32−6.20(m,2H),5.15(s,2H),4.02(s,2H),3.86(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 8.00(br s,1H),7.91(d,J=8.5 Hz,1H),7.64(d,J=2 .1 Hz,1H),7.56−7.48(m,2H),7.46−7.30(m,3H),7.01(dd,J=8.5,2.1 Hz,1H),5.22(s,2H),3.92(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 8.29−8.23(m,1H),7.83(d,J=8.2 Hz,1H),7.53−7.30(m,6H),7.12(dd,J=8.1,0.9 Hz,1H),6.70(dd,J =8.5,1.8 Hz,1H),6.58(s,1H),5.01(s,2H),4.84(s,2H),3.93(s,3H),2.80−2.58(m,1H),2.02−1.68(m,6H),1.57−1.09(m,4 H)
1H NMR(300MHz,クロロホルム−d)δ 8.56−8.47(m,1H),7.81(d,J=8.6 Hz,1H),7.57(dd,J=8.0,2.4 Hz,1H),7.53−7.46(m,2H),7.44−7.30(m,3H),7.15(d,J=8.0 Hz,1H),6.24(dd,J=8.6,2.2 Hz,1H),6.18(d,J=2.2 Hz,1H),5.12(s,2H),4.41(t,J=5.5 Hz,1H),4.33(d,J=5.3 Hz,2H),3.86(d,J=0.6 Hz.3H),2.72(tt,J=11.6,3.4 Hz,1H),2.03−1.70(m,5H),1.60−1.14(m,5H)
MS(ESI)m/z 744.3[M+H]+
HRMS(ESI)m/z 654.1688[M+H]+
MS(ESI)m/z 677.1 [M+Na]+
1H NMR(300MHz,クロロホルム−d)δ 7.97(s,1H),7.85(d,J=5.4 Hz,1H),7.46(d,J=8.2 Hz,1H),5.71(s,2H),3.63−3.45(m,2H),1.02−0.80(m,2H),−0.04(s,9H)
MS(ESI)m/z 446.3[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.83(s,1H),7.29(d,J=10.7 Hz,1H),6.85(d,J=7.2 Hz,1H),5.63(s,2H),4.03(br.s,2H),3.61−3.43(m,2H),1.00−0.79(m,2H),−0.05(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.83(s,1H),7.43−7.09(m,4H),6.85(d,J=7.2 Hz,1H),5.63(s,2H),4.03(s,5H),3.61−3.43(m,2H),1.00−0.79(m,2H),−0.05(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 8.02(s,1H),7.50(d,J=9.2 Hz,1H),7.20−6.96(m,5H),5.67−5.45(m,3H),4.29(d,J=14.1 Hz,1H),3.52−3.36(m,2H),2.48(m,1H),2.00−1.67(m,5H),1.52−1.17(m,5H),0.82(dd,J=9.3,7.2 Hz,2H),−0.06(s,9H)
MS(ESI)m/z 476.2 [M+Na]+1H NMR(300MHz,クロロホルム−d)δ 7.82(s,1H),7.41−7.19(m,5H),6.68(d,J=6.9 Hz,2H),5.63(s,2H),4.55(br.s,1H),4.43−4.35(m,2H),3.59−3.50(m,2H),2.62−2.44(m,1H),2.00−1.72(m,5H),1.54−1.32(m,5H),0.93−0.85(m,2H),−0.04(s,9H)
MS(ESI)m/z 767.2[M+H]+
HRMS(ESI)m/z 637. 1698[M+H]+
HRMS(ESI)m/z 639. 1854[M+H]+
MS(ESI)m/z 428.1[M+Na]+1H NMR(300MHz,クロロホルム−d)δ 8.22(d,J=1.0 Hz,1H),7.94(dd,J=8.8,1.9 Hz,1H),7.82(d,J=8.9 Hz,1H),7.42−7.29(m,10H),7.27−7.14(m,6H)
1H NMR(300MHz,クロロホルム−d)δ 7.93(d,J=0.9 Hz,1H),7.47(dd,J=8.5,0.7 Hz,1H),7.36−7.17(m,15H),6.51(dd,J=8.5,1.9 Hz,1H),5.72−5.63(m,1H)
1H NMR(300MHz,クロロホルム−d)δ 7.92(d,J=2.4 Hz,1H),7.36−7.15(m,16H),6.66(dd,J=8.4,6.7 Hz,1H)
1H NMR(300MHz,クロロホルム−d)δ 8.09(d,J=2.5,1H),8.02(dd,J=8.8,5.8 Hz,1H),7.81(br.s,1H),7.59(d,J=8.8 Hz,1H),7.37−7.24(m,9H),7.23−7.13(m,6H)
1H NMR(300MHz,クロロホルム−d)δ 8.06(d,J=2.2 Hz,1H),7.37−7.22(m,9H),7.21−7.12(m,7H),7.04(d,J=8.1Hz,2H),6.82(d,J=8.1Hz,2H),6.55−6.44(m,1H),5.29(d,J=14.0 Hz,1H),3.72(d,J=14.0 Hz,1H),2.56−2.34(m,1H),1.97−1.68(m,5H),1.53−1.16(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 7.91(d,J=2.4 Hz,1H),7.34(d,J=8.6 Hz,1H),7.31−7.12(m,15H),6.70(dd,J=8.6,6.5 Hz,1H),4.27(s,2H),3.99(br.s,1H),2.61−2.37(m,1H),1.98−1.68(m,5H),1.52−1.21(m,5H)
MS(ESI)m/z 879 [M+H]+
HRMS(ESI)m/z 637. 1707 [M+H]+
1H NMR(300MHz,CDCL3)δ 8.54(s,1H),7.65(dd,J=8.1,2.2 Hz,1H),7.22(d,J=8.1 Hz,1H),6.20− 6.10(m,1H),4.74(s,2H),2.44−2.33(m,2H),2.27−2.17(m,2H),1.85−1.74(m,2H),1.73−1.62(m,2H)
1H NMR(300MHz,クロロホルム−d)δ 8.42(d,J=2.4 Hz,1H),7.53(dd,J=8.0,2.4 Hz,1H),7.19(d,J=8.0 Hz,1H),4.74(s,2H),2.73−2.31(m,1H),2.00−1.68(m,5H),1.58−1.14(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 8.45(d,J=2.4 Hz,1H),7.56(dd,J=8.2,2.4 Hz,1H),7.40(d,J=8.2Hz,1H),4.67(s,2H),2.71−2.30(m,1H),2.10−1.72(m,5H),1.55−1.03(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 8.04(s,1H),7.39(d,J=8.1 Hz,1H),7.36−7.29(m,9H),7.24−7.16(m,6H),6.61(d,J=5.3 Hz,1H). MS(ESI)m/z 479.0,481.0 [M+Na]+
1H NMR(300MHz,クロロホルム−d)δ 7.91(d,J=1.0 Hz,1H),7.37−7.1 1(m,16H),5.75(dd,J=7.5,1.0 Hz,1H),3.63(s,2H). MS(ESI)m/z 394.0 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.06(d,J=1.0 Hz,1H),8.00(br.s,1H),7.62−7.54(m,1H),7.43(dd,J=10.2,0.5 Hz,1H),7.34−7.28(m,9H),7.28−7.21(m,6H)
MS(ESI)m/z 663.2 [M+H]+
MS(ESI)m/z 880.3 [M+H]+
HRMS(ESI)m/z 638.1754 [M+H]+
1H NMR(300MHz,CDCL3)δ 9.12(d,J=1.8 Hz,1H),8.73 d,J=1.8 Hz,1H),4.07(s,3H)
1H NMR(300MHz,CDCL3)δ 9.21(d,J=1.2 Hz,1H),8.81(d,J=1.2 Hz,1H),6.98−7.01(m,1H),4.05(s,3H),2.55−2.60(m,2H),2.34−2.38(m,2H),1.81−1.89(m,2H),1.70−1.77(m,2H)
1H NMR(300MHz,CDCL3)δ 9.23(d,J=1.8 Hz,1H),8.59(d,J=1.8 Hz,1H),4.05(s,3H),2.82−2.91(m,1H),1.31−1.99(m,10H)
1H NMR(300MHz,CDCl3)δ 8.57(d,J=1.2 Hz,1H),8.45(d,J=1.2 Hz,1H),4.84(s,2H),3.10(brs,1H,OH),2.76−2.85(m,1H),1.28−1.98(m,10H)
1H NMR(300MHz,クロロホルム−d)δ 8.32(d,J=1.4 Hz,1H),8.13(d,J=1.4 Hz,1H),8.09(s,1H),7.43(d,J=9.0 Hz,1H),7.28−7.07(m,15H),6.46(d,J=6.2 Hz,1H),5.18(d,J=15.2 Hz,1H),4.44(d,J=15.2 Hz,1H),2.82−2.60(m,1H),2.03−1.71(m,7H),1.57−1.26(m,3H)
1H NMR(300MHz,クロロホルム−d)δ 8.34(d,J=1.5 Hz,1H),8.27(s,1H),7.90(d,J=1.0 Hz,1H),7.27−7.11(m,15H),5.54(d,J=7.2 Hz,1H),4.93−4.82(m,1H),3.97(d,J=5.1 Hz,2H),2.88−2.66(m,1H),2.04−1.74(m,4H),1.70−1.30(m,6H)
HRMS(ESI)m/z 881.2724 [M+H]+
HRMS(ESI)m/z 639.1713 [M+H]+
6−ブロモ−1−トリチル−1H−ベンゾ[d]イミダゾール: 1H NMR(300MHz,クロロホルム−d)δ 7.89(s,1H),7.65(d,J=8.6,1H),7.42−7.32(m,8H),7.31−7.25(m,1H),7.24−7.14(m,7H),6.60(d,J=1.9 Hz,1H). 5−ブロモ−1−トリチル−1H−ベンゾ[d]イミダゾール: 1H NMR(300MHz,クロロホルム−d)δ 7.94(d,J=1.9 Hz,1H),7.89(s,1H),7.41−7.29(m,9H),7.24−7.1 1(m,6),7.02(dd,J=8.8,1.9 Hz,1H),6.35(d,J=8.8 Hz,1H)
HRMS(ESI)m/z 548.3528 [M+H]+
HRMS(ESI)m/z 883.2995 [M+Na]+
HRMS(ESI)m/z 619.1833[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.30(d,J=8.6,1H),7.70(d,J=1.9 Hz,1H),7.64−7.56(m,1H),7.25(d,J=7.5 Hz,1H),6.45(d,J=7.5 Hz,1H),5.43(s,2H),3.74− 3.53(m,2H),1.07−0.85(m,2H),0.00(s,9H)
MS(ESI)m/z 455.3[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.24(d,J=8.7 Hz,1H),7.12(d,J=7.5 Hz,1H),6.81(dd,J=8.6,2.3 Hz,1H),6.64(d,J=2.3 Hz,1H),6.34(d,J=7.5 Hz,1H),5.40(s,2H),4.13(br.s,2H),3.72−3.41(m,1H),1.01−0.89(m,2H),−0.01(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 8.44(d,J=8.7 Hz,1H),8.33(s,1H),8.07(d,J=2.1 Hz,1H),7.47(dd,J=8.7,2.1 Hz,1H),7.27(d,J=7.5 Hz,1H),6.55(d,J=7.5 Hz,1H),5.44(s,2H),3.76−3.48(m,2H),1.04−0.85(m,2H),−0.00(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 8.41(d,J=8.4 Hz,1H),7.25(d,J=7.5 Hz,1H),7.18−6.99(m,6H),6.42(d,J=7.5 Hz,1H),5.43(s,2H),4.94(s,2H),3.75−3.54(m,2H),2.61−2.39(m,1H),1.98−1.67(m,6H),1.51−1.14(m,4H),1.06−0.86(m,2H),0.01(s,8H)
MS(ESI)m/z 333.2 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 10.72(s,1H),8.39(d,J=8.5 Hz,1H),7.24−6.92(m,7H),6.47(d,J=7.2 Hz,1H),5.08−4.68(m,3H),4.21−3.96(m,2H),2.58−2.39(m,1H),2.37−2.20(m,1H),2.04−1.70(m,5H),1.58−1.14(m,6H). HRMS(ESI)m/z 646.1826 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 10.68(s,1H),8.42(d,J= 8.3 Hz,1H),8.08(s,1H),7.49−7.30(m,2H),7.13(d,J=7.8 Hz,2H),7.01(d,J=7.8 Hz,2H),5.07−4.67(m,3H),4.23−3.98(m,2H),2.58 −2.42(m,1H),2.42−2.22(m,1H),2.04−1.66(m,6H),1.53−1.17(m,5H). HRMS(ESI)m/z 647.1745 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.75(d,J=2.2 Hz,1H),7.76(dd,J=8.2,2.2 Hz,1H),7.64(d,J=8.2 Hz,1H),6.43−6.30(m,1H),2.48−2.35(m,2H),2.35−2.23(m,2H),1.92−1.78(m,2H),1.77−1.66(m,2H)
(5−シクロヘキシルピリジン−2−イル)メタンアミン: 1H NMR(300MHz,クロロホルム−d)δ 8.41(d,J=2.3 Hz,1H),7.49(dd,J=8.0,2.3 Hz,1H),7.20(d,J=8.0 Hz,1H),3.94(s,2H),2.65−2.40(m,1H),2.04−1.66(m,7H),1.54−1.10(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 8.47(d,J=2.2 Hz,1H),8.23(d,J=8.8 Hz,1H),8.01(s,1H),7.54(dd,J=8.0,2.2 Hz,1H),7.25(d,J=8.0 Hz,1H),7.09(dd,J=8.8,2.2 Hz,1H),6.68(d,J=2.3 Hz,1H),5.74(t,J=5.0 Hz,1H),5.54(s,2H),4.53(d,J=4.9 Hz,2H),3.74(dd,J=8.7,8.0 Hz,2H),2.67−2.48(m,1H),2.03−1.73(m,5H),1.58−1.19(m,5H),1.00(dd,J=8.7,8.0 Hz,2H),0.00(s,9H)
HRMS(ESI)m/z 778.2611 [M+H]+
MS(ESI)m/z 678.3 [M+H]+
HRMS(ESI)m/z 648.1850 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.87−8.70(m,2H),7.10−6.98(m,1H),2.61−2.49(m,2H),2.43−2.31(m,2H),1.93−1.79(m,2H),1.78−1.68(m,2H)
1H NMR(300MHz,クロロホルム−d)δ 8.63(d,J=1.5 Hz,1H),8.47(d,J=1.5 Hz,1H),6.78−6.70(m,1H),4.00(s,2H),2.59−2.47(m,2H),2.35−2.23(m,2H),1.89−1.62(m,6H)
1H NMR(300MHz,クロロホルム−d)δ 8.68(s,1H),8.56(s,1H),8.25(d,J=8.8 Hz,1H),8.01(s,1H),7.10(dd,J=8.8,2.4 Hz,1H),6.87−6.77(m,1H),6.70(d,J=2.4 Hz,1H),5.54(s,2H),4.65−4.54(m,2H),3.83−3.66(m,2H),2.65−2.45(m,2H),2.41−2.25(m,2H),1.90−1.78(m,2H),1.78−1.67(m,2H),1.15−0.90(m,2H),0.00(s,9H)
MS(ESI)m/z 777.3 [M+H]+
MS(ESI)m/z 779.3 [M+H]+
MS(ESI)m/z 679.2 [M+H]+
HRMS(ESI)m/z 649.1687 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.43−8.35(m,2H),8.10(d,J=8.9 Hz,1H),4.90(s,2H),1.64(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 7.68(d,J=8.3 Hz,1H),6.71(dd,J=8.3,2.0 Hz,1H),6.63(d,J=2.0 Hz,1H),4.64(s,2H),4.22(br.s,2H),1.60(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 8.58(br.s,1H),8.11(d,J=1.8 Hz,1H),7.92(d,J=8.3 Hz,1H),7.53(dd,J=8.3,1.8 Hz,1H),4.80(s,2H),1.62(s,9H)
MS(ESI)m/z 518.4[M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.46(s,1H),7.69(d,J=8.4 Hz,1H),7.53(dd,J=8.1,2.2 Hz,1H),7.24(d,J=8.1 Hz,1H),6.75(d,J=8.4 Hz,1H),6.59(s,1H),5.55(br.s,1H),4.64(s,2H),4.48(d,J=4.2 Hz,2H),2.66−2.45(m,1H),2.02−1.73(m,6H),1.60(s,9H),1.50−1.31(m,4H)
HRMS(ESI)m/z 635.1975 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 7.71(dd,J=8.6,7.2 Hz,1H),7.35−7.28(m,1H),4.74(s,2H),1.62(s,9H)
1H NMR(300MHz,クロロホルム−d)δ 8.48(d,J=2.2 Hz,1H),7.54(dd,J=8.0,2.2 Hz,1H),7.47(d,J=10.4 Hz,1H),7.27−7.22(m,1H),6.62(d,J=7 .1Hz,1H),5.79− 5.64(m,1H),4.62(s,2H),4.52(d,J=5.1 Hz,2H),2.67−2.47(m,1H),2.02−1.71(m,6H),1.60(s,9H),1.53−1.31(m,4H). MS(ESI)m/z 440.4 [M+H]+
HRMS(ESI)m/z 653. 1682 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 10.99(s,1H),8.04(d,J=8.7 Hz,1H),7.84(d,J=2.2 Hz,1H),7.72(dd,J=8.7,2.2 Hz,1H),4.04(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 7.99−7.81(m,3H),7.57−7.25(m,5H),5.30(s,2H),3.96(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 7.80(d,J=8.6 Hz,1H),7.54(m,2H),7.47−7.25(m,5H),6.27(m,2H),5.16(s,2H),4.06−3.99(m,2H),3.87(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 7.99(s,1H),7.91(d,J=8.4 Hz,1H),7.64(d,J=2.0 Hz,1H),7.53(m,2H),7.49−7.20(m,3H),7.01(dd,J=8.5,2.0 Hz,1H),5.22(s,2H),4.02−3.82(s,3H)
1H NMR(300MHz,クロロホルム−d)δ 7.81(d,J=8.2 Hz,1H),7.43−7.30(m,5H),7.14(d,J=8.2,2H) 7.05(d,J=8.2 Hz,2H),6.72(d,J=8.2 Hz,1H),6.49(s,1H),4.93(s,2H),4.84(s,2H),3.92(s,3H),2.57−2.41(m,1H),1.98−1.69(m,5H),1.2−1.5(m,5H)
1H NMR(300MHz,クロロホルム−d)δ 7.81(d,J=8.5 Hz,1H),7.51(d,J=7.4 Hz,2H),7.46−7.16(m,7H),6.29(dd,J=8.5,2.4 Hz,1H),6.17(d,J=2.4 Hz,1H),5.12(s,2H),4.41(br,1H),4.31(s,2H),3.86(s,3H),2.52(m,1H),1.98−1.69(m,5H),1.50−1.19(m,5H)
MS(ESI):[M+H]+m/z 743.2
HRMS(ESI+)m/z 653.1732 [M+H]+
1H NMR(300MHz,クロロホルム−d)δ 8.57(d,J=1.7 Hz,1H),7.83(d,J=8.3,1H),7.78(dd,J=8.2,2.3,1H),7.47−7.31(m,5H),7.18(d,J=8.2 Hz,1H),6.96(d,J=1.8 Hz,1H),6.90(dd,J= 8.3,1.8 Hz,1H),5.13(s,3H),4.94(s,3H),3.93(s,3H)。
1H NMR(300MHz,クロロホルム−d)δ 8.66(d,J=2.4 Hz,1H),7.83(d,J=8.3,1H),7.78(dd,J=8.2,2.4,1H),7.55−7.46(m,2H),7.44−7.26(m,3H),7.18(d,J=8.2 Hz,1H),6.26(dd,J=8.3,2.2,1H),6.20(d,J=2.2 Hz,1H),5.25(br,1H),5.15(s,2H),4.44(d,J=4.4 Hz,2H),3.86(s,3H)。
1H NMR(300MHz,クロロホルム−d)δ 8.53(m,1H),7.98−7.66(m,2H),7.62−7.05(m,6H),7.01−6.69(m,2H),5.4−5.06(m,2H),5.05−4.70(m,3H),4.28−3.70(m,5H),1.94−1.43(m,2H)。
MS(ESI)[M+H]+ m/z 742.2
MS(ESI):[M+H]+m/z 654.3
1H NMR(300MHz,CDCl3)δ 8.42(d,J=2.2 Hz,1H),7.50(dd,J=8.0,2.2 Hz,1H),7.34(d,J=8.0 Hz,1H),4.53(s,2H),2.64−2.38(m,1H),1.91−1.71(m,5H),1.50−1.25(m,5H)
1H NMR(300MHz,CDCl3)δ 8.49−8.33(m,1H),8.20(br,1H),8.03−7.79(m,2H),7.55−7.18(m,5H),5.39(s,2H)
1H NMR(300MHz,CDCl3)δ 8.36(d,J=2.0 Hz,1H),7.90−7.79(m,2H),7.50(dd,J=8.0,2.0 Hz,1H),7.47−7.35(m,5H),7.35−7.26(m,2H),5.42(d,J=14.6 Hz,1H),5.37(s,2H),4.58(d,J=14.6 Hz,1H),2.61−2.42(m,1H),1.92−1.72(m,5H),1.52−1.29(m,5H)
1H NMR(300MHz,CDCl3)δ 8.47(d,J=2.1 Hz,1H),7.73(d,J=8.4 Hz,1H),7.71−7.63(m,1H),7.52(dd,J=8.0,2.1 Hz,1H),7.24(d,J=8.0 Hz,1H),6.66(m,1H),5.51(br,1H),4.52(d,J=5.3 Hz,2H),3.87(s,3H),2.56(s,1H),1.96 −1.76(m,5H),1.53−1.35(m,5H)
1H NMR(300MHz,CDCl3)δ 8.24(s,1H),7.85−7.69(m,2H),7.5 1−7.38(m,1H),7.34−7.12(m,2H),5.26(d,J=14.9 Hz,1H),4.90(t,J=7 .8 Hz,1H),4.45(d,J=14.9 Hz,1H),4 .18−3.95(m,3H),3.91(s,3H),4.03−3.85(m,1H),2.55−2.38(m,1H),2.36−2 .15(m,1H),1.96−1.65(m,6H),1.46−1.17(m,5H)
MS(ESI):[M+H]+m/z 642.2
1H NMR(300MHz,CDCl3)δ 8.16(d,J=2.8 Hz,1H),7.99−7.92(m,1H),7.52−7.44(m,2H),7.41−7.30(m,3H),6.96(dd,J=8.5,2.8 Hz,1H),5.42(s,2H),4.14(s,2H)
1H NMR(300MHz,CDCl3)δ 8.78(d,J=2.1 Hz,1H),8.54−8.37(m,2H),8.22(d,J=8.6 Hz,1H),7.55−7.45(m,2H),7.45−7.34(m,3H),5.47(s,2H)
1H NMR(300MHz,CDCl3)δ 8.63(d,J=2.3 Hz,1H),8.37(d,J=2.2 Hz,1H),8.17(d,J=8.3 Hz,1H),7.82(dd,J=8.3,2.3 Hz,1H),7.53−7.46(m,3H),7.43−7.33(m,3H),7.23(d,J=7.9 Hz,1H),5.46(s,2H),5.02(s,2H),2.59−2.46(m,1H),1.94−1.77(m,5H),1.49−1.34(m,5H)
1H NMR(300MHz,CDCl3)δ 8.44(s,1H),8.20(d,J=2.7 Hz,1H),7.98(d,J=8.6 Hz,1H),7.58−7.30(m,6H),7.22(d,J=8.0 Hz,1H),6.90(dd,J=8.6,2.7 Hz,1H),5.66(br,1H),5.41(s,2H),4.46(d,J=4.9 Hz,2H),2.57−2.45(m,1H),1.99−1.79(m,5H),1.53−1.32(m,5H)
MS(ESI):[M+H]+m/z 625.2.
1H NMR(300MHz,CDCl3)δ 9.12(d,J=1.8 Hz,1H),8.73(d,J=1.8 Hz,1H),4.07(s,3H)
1H NMR(300MHz,CDCl3)δ 9.21(d,J=1.2 Hz,1H),8.81(d,J=1.2 Hz,1H),6.98−7.01(m,1H),4.05(s,3H),2.55−2.60(m,2H),2.34−2.38(m,2H),1.81−1.89(m,2H),1.70−1.77(m,2H)
1H NMR(300MHz,CDCl3)δ 9.23(d,J=1.8 Hz,1H),8.59(d,J=1.8 Hz,1H),4.05(s,3H),2.82−2.91(m,1H),1.31−1.99(m,10H).
1H NMR(300MHz,CDCl3)δ 8.57(d,J=1.2 Hz,1H),8.45(d,J=1.2 Hz,1H),4.84(s,2H),3.10(brs,1H,OH),2.76−2.85(m,1H),1.28−1.98(m,10H)
1H NMR(300MHz,CDCl3)δ 8.65(d,J=1.2 Hz,1H),8.50(d,J=1.2 Hz,1H),5.36(s,2H),3.14(s,3H),2.77−2.86(m,1H),1.26−1.98(m,10H)
1H NMR(300MHz,CDCl3)δ 8.48(s,1H),8.40(d,J=1.2 Hz,1H),7.86(d,J=8.1 Hz,1H),7.33−7.41(m,10H),6.99(s,1H),6.93(d,J=8.1 Hz,1H),5.35(s,2H),5.09(s,2H),4.99(s,2H),2.72−2.81(m,1H),1.26−1.96(m,10H).
1H NMR(300MHz,CDCl3)δ 8.52(d,J=1.2 Hz,1H),8.43(d,J=1.2 Hz,1H),7.87(d,J=9.0 Hz,1H),7.28−7.50(m,10H),6.27−6.31(m,2H),5.32(s,2H),5.15−5.19(m,3H),4.48(d,J=4.5 Hz,2H),2.73−2.81(m,1H),1.28−1.97(m,10H).
1H NMR(300MHz,CDCl3)δ 8.39(s,1H),8.35(s,1H),7.84(d,J=8.4 Hz,1H),7.33−7.44(m,10H),6.92(d,J=1.8 Hz,1H),6.82(dd,J=1.8,8,4 Hz,1H),5.37(s,2H),5.21(d,J=12.3 Hz,1H),5.12(d,J=12.3 Hz,1H),4.99(d,J=15.9 Hz,1H),4.88−4.94(m,1H),4.76(d,J=15.9 Hz,1H),4.01−4.09(m,1H),3.88−3.98(m,1H),2.69−2.78(m,1H),1.26−2.10(m,12H)
1H NMR(300MHz,CDCl3)δ 11.23(brs,1H,OH),8.83(s,1H),8.43(s,1H),7.70(d,J=8.4 Hz,1H),6.69(dd,J=1.8,8.4 Hz,1H),6.61(d,J=1.8 Hz,1H),4.95−5.07(m,3H),4.10−4.18(m,1H),3.96−4.05(m,1H),2.79−2.90(m,1H),2.20−2.31(m,1H),1.25−2.08(m,11H). MS(ESI)m/z 641.0[M+H]+
1H NMR(300MHz,CDCl3)δ 9.01(s,2H),4.10(s,3H).
1H NMR(300MHz,CDCl3)δ 8.91(s,2H),6.42−6.44(m,1H),4.09(s,3H),2.43−2.48(m,2H),2.28−2.34(m,2H),1.84−1.88(m,2H),1.71−1.76(m,2H).
1H NMR(300MHz,CDCl3)δ 8.78(s,2H),4.08(s,3H),2.61−2.70(m,1H),1.25−1.96(m,10H).
1H NMR(300MHz,CDCl3)δ 8.59(s,2H),4.83(s,2H),3.71(brs,1H,OH),2.53−2.62(m,1H),1.77−1.97(m,5H),1.25−1.54(m,5H)
1H NMR(300MHz,CDCl3)δ 8.63(s,2H),5.43(s,2H),3.22(s,3H),2.54−2.63(m,1H),1.76−1.98(m,5H),1.25−1.54(m,5H)
1H NMR(300MHz,CDCl3)δ 8.52(s,2H),7.86(d,J=8.1Hz,1H),7.32−7.42(m,10H),7.23(d,J=1.2 Hz,1H),7.11(dd,J=1.2,8.1 Hz,1H),5.35(s,2H),5.13(s,2H),5.07(s,2H),2.48−2.58(m,1H),1.76−1.96(m,5H),1.24−1.53(m,5H)
1H NMR(300MHz,CDCl3)δ 8.59(s,2H),7.88(d,J=9.3 Hz,1H),7.49−7.52(m,2H),7.30−7.43(m,8H),6.3 1−6.35(m,2H),5.58(t,J=5.4 Hz,1H,NH),5.33(s,2H),5 .18(s,2H),4.56(d,J=5.4 Hz,2H),2.52−2.61(m,1H),1.77−1.98(m,5H),1.26−1.54(m,5H)
1H NMR(300MHz,CDCl3)δ 8.49(s,2H),7.83(d,J=8.4 Hz,1H),7.32−7.45(m,10H),7.15(d,J=1.8 Hz,1H),6.98(dd,J=1.8,8.4 Hz,1H),5.37(s,2H),5.25(d,J=12.6 Hz,1H),5.16(d,J=12.6 Hz,1H),5.09(d,J=17.1 Hz,1H),4.98−5.04(m,1H),4.82(d,J=17.1 Hz,1H),3.94−4.13(m,2H),2.47−2.56(m,1H),2.11−2.21(m,1H),1.24−1.95(m,11H)
1H NMR(300MHz,CDCl3)δ 11.08(brs,1H,OH),8.63(s,2H),7.83(d,J=8.4 Hz,1H),6.82−6.91(m,2H),5.12−5.32(m,3H),4.90(d,J=17.1 Hz,1H),4.02−4.23(m,2H),2.53−2.64(m,1H),2.35−2.46(m,1H),1.76−2.20(m,6H),1.24−1.54(m,5H). MS(ESI)m/z 641.1[M+H]+
1H NMR(300MHz,CDCl3)δ 8.18(d,J=8.7 Hz,1H),7.69(d,J=8.7 Hz,1H),4.09(s,3H)
1H NMR(300MHz,CDCl3)δ 8.11(d,J=8.7 Hz,1H),7.67(d,J=8.7 Hz,1H),6.95−6.98(m,1H),4.08(s,3H),2.65−2.72(m,2H),2.32−2.40(m,2H),1.82−1.91(m,2H),1.70−1.79(m,2H)
1H NMR(300MHz,CDCl3)δ 8.12(d,J=8.7 Hz,1H),7.48(d,J=8.7 Hz,1H),4.08(s,3H),3.06−3.17(m,1H),2.00−2.09(m,2H),1.88−1.98(m,2H),1.78−1.86(m,1H),1.27−1.68(m,5H)
1H NMR(300MHz,CDCl3)δ 7.42(d,J=9.0 Hz,1H),7.36(d,J=9.0 Hz,1H),4.95(s,2H),3.59(brs,1H,OH),2.93−3.03(m,1H),1.98−2.06(m,2H),1.87−1.95(m,2H),1.25−1.86(m,6H)
1H NMR(300MHz,CDCl3)δ 7.62(d,J=9.0 Hz,1H),7.43(d,J=9.0 Hz,1H),5.54(s,2H),3.15(s,3H),2.97−3.06(m,1H),1.98−2.06(m,2H),1.88−1.96(m,2H),1.78−1.86(m,1H),1.27−1.68(m,5H)
1H NMR(300MHz,CDCl3)δ 7.86(d,J=8.1Hz,1H),7.31−7.48(m,12H),7.05(d,J=1.8 Hz,1H),6.96(dd,J=1.8,8.1 Hz,1H),5.35(s,2H),5.13(s,2H),5.10(s,2H),2.94−3.02(m,1H),1.97−2.05(m,2H),1.86−1.94(m,2H),1.26−1.84(m,6H)
1H NMR(300MHz,CDCl3)δ 7.87(d,J=8.4 Hz,1H),7.29−7.49(m,12H),6.25−6.30(m,2H),5.49(t,J=5.4 Hz,1H,NH),5.32(s,2H),5.13(s,2H),4.64(d,J=5.4 Hz,2H),2.92−3.02(m,1H),1.98−2.05(m,2H),1.87−1.96(m,2H),1.77−1.85(m,1H),1.28−1.68(m,5H)
1H NMR(300MHz,CDCl3)δ 7.83(d,J=8.4 Hz,1H),7.30−7.43(m,12H),6.93(d,J=1.8 Hz,1H),6.89(dd,J=1.8,8.4 Hz,1H),5.37(s,2H),5.19(d,J=12.3 Hz,1H),5.06−5.14(m,2H),4.90−5.00(m,2H),3.90−4.08(m,2H),2.91−3.01(m,1H),1.24−2.13(m,12H)
1H NMR(300MHz,CDCl3)δ 11.29(brs,1H,OH),7.94(d,J=8.1 Hz,1H),7.78(d,J=8.4 Hz,1H),7.59(d,J=8.4 Hz,1H),6.55−6.63(m,2H),5.33(d,J=13.8 Hz,1H),5.11(d,J=13.8 Hz,1H),4.97(t,J=7.8 Hz,1H),3.94−4.15(m,2H),3.03−3.14(m,1H),1.26−2.28(m,12H). HRMS(ESI)m/z 641.1491 [M+H]+
1H NMR(300MHz,CDCl3)δ 8.39(d,J=2.3 Hz,1H),7.8 1(d,J=8.2 Hz,1H),7.57−7.24(m,6H),7.19(d,J=8.0 Hz,1H). 6.93(d,J=2.0 Hz,1H),6.89(dd,J=8.2,2.0 Hz,1H),5.06(s,2H),4.99(s,3H),3.91(s,3H),2.60−2.47(m,1H),1.96−1.71(m,5H),1.52−1.33(m,5H)
1H NMR(300MHz,CDCl3)δ 8.45(d,J=2.2 Hz,1H),7.82(dd,J=8.5,0.7 Hz,1H),7.60−7.46(m,3H),7.45 −7.26(m,3H),7.25−7.17(m,1H),6.38−6.15(m,2H),5.35(br,1H),5.14(s,2H),4.45(s,2H),3.86(s,3H),2.63−2.48(m,1H),1.97−1.71(m,5H),1.53−1.31(m,5H)
1H NMR(300MHz,CDCl3)δ 8.35(d,J=2.2 Hz,1H),7.83−7.76(m,1H),7.53−7.30(m,6H),7.13(d,J=8.1 Hz,1H),6.83(d,J=1.9 Hz,1H),6.81−6.73(m,1H),5.18(d,J=12.6 Hz,1H),5.07(d,J=12.6 Hz,1H),4.99−4.80(m,3H),4.20−3.85(m,2H),3.94(s,3H),2.58−2.45(m,1H),2.14−1.98(m,1H),1.96−1.51(m,6H),1.51−1.28(m,5H)
MS(ESI):[M+H]+m/z 730.3
MS(ESI):[M+H]+m/z 834.9
MS(ESI):[M+H]+m/z 654.9
MS(ESI):[M+H]+m/z 654.9
MS(ESI):[M+H]+m/z m/z=671.0
1H NMR(300MHz,CDCl3)δ 8.21−8.00(m,3H),7.52−7.35(m,5H),5.45(s,2H)
1H NMR(300MHz,CDCL3)δ 7.81(dd,J=7.8 Hz,8.4 Hz,1H),7.55−7.29(m,5H),6.47−6.29(m,2H),5.35(s,2H),4.17(s,2H)
1H NMR(300MHz,CDCL3)δ8.04(dd,J=8.3,8.2 Hz,1H),7.97(s,1H),7.67(dd,J=11.9,2.0 Hz,1H),7.51−7.35(m,5H),7.33−7.28(m,1H),5.40(s,2H)
1H NMR(300MHz,CDCL3)δ 8.41(s,1H),7.99(m,1H),7.65−6.95(m,9H),5.40(s,2H),5.02(s,2H),2.65−2.53(m,1H),2.05−1.65(m,5H),1.56−1.20(m,5H)
1H NMR(300MHz,CDCL3)δ 8.44(d,J=1.2 Hz,1H),7.81(dd,J=8.7 Hz,8.4 Hz,1H),7.54−7.41(m,4H),7.40−7.29(m,3H),6.45(d,J=8.9 Hz,1H),6.33(d,J=13.5 Hz,1H),5.63(s,1H),5.33(s,2H),4.42(s,2H),2.64−2.52(m,1H),1.98−1.69(m,5H),1.58−1.22(m,5H)
1H NMR(300MHz,CDCL3)δ 8.35(s,1H),7.98(dd,J=8.2Hz,8.0 Hz,1H),7.55−7.34(m,6H),7.21−7.05(m,3H),5.39(s,2H),5.04(m,1H),4.91(s,2H),4.26−3.99(m,2H),2.64−2.46(m,1H),2.46−2.22(m,1H),1.94−1.70(m,6H),1.5 1−1.33(m,5H)
MS(ESI):[M+H]+m/z 641.9
1H NMR(300MHz,CDCL3)δ 9.56(s,1H),8.19(s,1H),7.59−7.31(m,8H),7.26−7.03(m,2H),5.19(d,J=14.8 Hz,1H),4.99(s,2H),4 .80−4.92(m,1H),4.47(d,J=14.8 Hz,1H),4 .17−4.06(m,1H),4.06−3.90(m,1H),2.60−2.35(m,1H),2.34−2.10(m,1H),2.00−1.69(m,6H),1.54−1.26(m,5H)
MS(ESI):[M+H]+m/z 656.9
1H NMR(300MHz,CDCL3)δ 9.56(s,1H),8.19(s,1H),7.59−7.31(m,8H),7.26−7.03(m,2H),5. 19(d,J=14.8 Hz,1H),4.99(s,2H),4 .80−4.92(m,1H),4.47(d,J=14.8 Hz,1H),4 .17−4.06(m,1H),4.06−3.90(m,1H),2.60−2.35(m,1H),2.34−2.10(m,1H),2.00−1.69(m,6H),1.54−1.26(m,5H)
MS(ESI):[M+H]+ 641.0
1H NMR(300MHz,CDCL3)δ 10.12(s,1H),8.35(d,J=2.2 Hz,1H),8.20(d,J=8.3 Hz,1H),7.56−7.35(m,6H),7.16(d,J=8.0 Hz,1H),7.00(d,J=1.9 Hz,1H),6.86(dd,J=8.3,1.9Hz,1H),5.22(d,J=11.4 Hz,1H),5.11(d,J=11.4 Hz,1H),5.02−4.76(m,3H),4.26−3.90(m,2H),3.80(s,3H),2.66−2.42(m,1H),2.31−2.00(m,1H),1.96−1.69(m,6H),1.57−1.15(m,5H)
MS(ESI)m/z 759.0[M+H]+
1H NMR(300MHz,CDCL3)δ 10.91(s,1H,OH),8.42(d,J=1.2 Hz,1H),8.37(d,J=1.2 Hz,1H),7.89(d,J=8.4 Hz,1H),6.86(d,J=2.4 Hz,1H),6.80(dd,J=2.4,8.4 Hz,1H),5.02−5.12(m,2H),4 .80(d,J=15.3 Hz,1H),4.12−4.20(m,1H),3.93−4.07(m,4H),2.68−2.78(m,1H),2.27−2.38(m,1H),2.04−2.14(m,1H),1.84−1.98(m,4H),1.73−1.82(m,1H),1.27−1.58(m,5H)
1H NMR(300MHz,CDCL3)δ 9.23(d,J=1.5 Hz,1H),8.80(d,J=1.5 Hz,1H),6.92−6.95(m,1H),4.05(s,3H),2.84−2.91(m,2H),2.64−2.71(m,2H),2.06−2.17(m,2H)
1H NMR(300MHz,CDCl3)δ 9.23(d,J=1.5 Hz,1H),8.59(d,J=1.5 Hz,1H),4.05(s,3H),3.28−3.38(m,1H),2.11−2. 19(m,2H),1.72−1.94(m,6H)
1H NMR(300MHz,CDCL3)δ 8.54(d,J=1.8 Hz,1H),8.44(d,J=1.8 Hz,1H),4.82(d,J=4.2 Hz,2H),3.19−3.30(m,1H),3.07(t,J= 4.2 Hz,1H,OH),2.08−2.16(m,2H),1.71−1.91(m,6H)
1H NMR(300MHz,CDCL3)δ 8.65(d,J=1.2 Hz,1H),8.50(d,J=1.2 Hz,1H),5.35(s,2H),3.22−3.32(m,1H),3.13(s,3H),2.07−2.16(m,2H),1.71−1.92(m,6H)
1H NMR(300MHz,CDCl3)δ 8.48(s,1H),8.39(d,J=1.8 Hz,1H),7.87(d,J=8.7 Hz,1H),7.32−7.42(m,10H),7.00(s,1H),6.93(d,J=8.7 Hz,1H),5.35(s,2H),5.09(s,2H),4.98(s,2H),3.16−3.27(m,1H),2.05−2.14(m,2H),1.69−1.90(m,6H)
1H NMR(300MHz,CDCl3)δ 8.52(d,J=1.2 Hz,1H),8.44(d,J=1.2 Hz,1H),7.87(d,J=8.4 Hz,1H),7.29−7.50(m,10H),6.26−6.31(m,2H),5.32(s,2H),5.17(t,J= 5.4 Hz,1H,NH),5.15(s,2H),4.48(d,J=5.4 Hz,2H),3.18−3.28(m,1H),2.10−2.15(m,2H),1.70−1.91(m,6H)
1H NMR(300MHz,CDCl3)δ 8.39(s,1H),8.35(d,J=1.8 Hz,1H),7.84(d,J=8.4 Hz,1H),7.33−7.44(m,10H),6.93(d,J=1.8 Hz,1H),6.82(dd,J=1.8,8.4 Hz,1H),5.37(s,2H),5.21(d,J=12.6 Hz,1H),5.13(d,J=12.6 Hz,1H),4.88−5.01(m,2H),4.76(d,J=15.0 Hz,1H),4.00−4.10(m,1H),3.89−3.98(m,1H),3.15−3.25(m,1H),2.01−2.13(m,3H),1.67−1.89(m,7H)
1H NMR(300MHz,CDCl3)δ 11.29(brs,1H,OH),8.86(s,1H),8.44(s,1H),7.69(d,J=8.4 Hz,1H),6.69(d,J=8.4 Hz,1H),6.60(s,1H),4.95−5.08(m,3H),4.10−4. 18(m,1H),3.98−4.05(m,1H),3.25−3.37(m,1H),1.72−2.29(m,10H). MS(ESI)m/z 627.0[M+H]+
1H NMR(300MHz,CDCl3)δ 8.43(d,J=1.2 Hz,1H),8.36(d,J=1.2 Hz,1H),8.21(d,J=8.1 Hz,1H),7.44−7.48(m,5H),7.23(d,J=1.5 Hz,1H),6.98(dd,J=1.5,8.1 Hz,1H),5.39(d,J=11.4 Hz,1H),5.29(d,J=11.4 Hz,1H),4.94−5.03(m,2H),4.80(d,J=15.6 Hz,1H),4.00−4.15(m,2H),2.70−2.80(m,1H),2.12−2.22(m,1H), 1.25−1.98(m,11H)
1H NMR(300MHz,CDCl3)δ 10.07(s,1H,NH),8.40(s,1H),8.34(s,1H),8.24(d,J=8.4 Hz,1H),7.35−7.42(m,8H),7.21−7.25(m,2H),7.00(d,J=1.8 Hz,1H),6.89(dd,J=1.8,8.4 Hz,1H),5.13(d,J=12.0 Hz,1H),4.87−5.06(m,5H),4.75(d,J=15.3 Hz,1H),3.95−4.12(m,2H),2.69−2.78(m,1H),2.07−2.15(m,1H),1.25−1.97(m,11H)
1H NMR(300MHz,CDC13)□11.61(brs,1H,OH),10.35(brs,1H,OH),8.47(s,1H),8.39(s,1H),7.56(d,J=7.8Hz,1H),6.85(s,1H),6.74(d,J=7.8Hz,1H),5.08−5.15(m,1H),4.96(s,2H),3.99−4.19(m,2H),2.69−2.80(m,1H),2.26−2.38(m,1H),1.23−2.17(m,11H). MS(ESI+)m/z 656.0[M+H]+
1H NMR(300MHz,CDCl3)δ 8.18−8.11(m,2H),7.99(s,1H),7.73−7.66(m,2H),7.51−7.34(m,5H),5.39(s,2H)
1H NMR(300MHz,CDCl3)δ 8.32(s,1H),8.07(d,J=8.5 Hz,2H),7.52−7.34(m,6H),7.25(d,J=8.5 Hz,2H),7.18(d,J=8.0 Hz,1H),5.37(s,2H),5.04−4.95(m,1H),4.95−4.84(m,2H),4.18−4.08(m,1H),4.08−4.00(m,1H),2.58−1.44(m,1H),2.38−2.23(m,1H),1.97−1.77(m,6H),1.50−1.31(m,5H)
MS(ESI+)m/z 624.0[M+H]+
1H NMR(300MHz,CDCL3)δ 8.50(s,1H),7.75−7.53(m,1H),7.41−7.11(m,1H),6.34−6.06(m,1H),4.70(s,2H),2.89−2.31(m,4H),2.03−1.98(m,2H)
1H NMR(300MHz,CDCl3)δ 8.41(d,J=1.8 Hz,1H),7.53(dd,J=8.0,1.8 Hz,1H),7.19(d,J=8.0 Hz,1H),4.73(s,2H),2.61−2.47(m,1H),1.91−1.79(m,4H),1.48−1.33(m,4H)
1H NMR(300MHz,CDCl3)δ 8.46(s,1H),7.69−7.46(m,1H),7.46−7.17(m,1H),4.65(s,2H),3.10−2.90(m,1H),2.27−1.40(m,8H)
1H NMR(300MHz,CDCl3)δ 8.49(d,J=2.2 Hz,1H),7.77(dd,J=8.4,1.7 Hz,1H),7.71(dd,J=12.3,1.7 Hz,1H),7.54(dd,J=8.0,2.2 Hz,1H),7.47−7.30(m,5H),7.23(d,J=8.0 Hz,1H),6.65(dd,J=8.5,8.4 Hz,1H),5.57(s,1H),5.32(s,2H),4.51(m,2H),3.08−2.95(m,1H),2.17−2.07(m,2H),1.86−1.68(m,4H),1.63−1.53(m 2H)
1H NMR(300MHz,CDCl3)δ 8.31(s,1H),7.91−7.77(m,2H),7.52(d,J=7.8 Hz,1H),7.47−7.29(m,6H),7.26−7.20(m,1H),5.37(s,2H),5.35−5.24(m 1H),4.98−4.89(m,1H),4.49(d,J=14.8 Hz,1H),4.17−4.04(m,2H),3.04−2.89(m,1H),2.39−2.19(m,1H),2.14−2.02(m,1H),1.94−1.65(m,6H),1.60−1.46(m ZH)
MS(ESI+):[M+H]+ m/z 627.9
1H NMR(300MHz,CDCl3)δ 8.42(d,J=1.8 Hz,1H),7.86(d,J=8.3,1H),7.52(dd,J=8.0,1.8 Hz,1H),7.43−7.30(m,10H),7.19(d,J=7.9 Hz,1H),6.98(s,1H),6.90(d,J=8.3 Hz,1H),5.35(s,2H),5.05(s,2H),4.99(s,2H),3.07−2.92(m,1H),2.15−2.07(m,2H),1.88−1.68(m,4H),1.63−1.51(m,2H)
1H NMR(300MHz,CDCl3)δ 8.47(d,J=1.8 Hz,1H),7.87(d,J=8.4,1H),7.57−7.23(m,11H),7.19(d,J=7.9 Hz,1H),6.30−6.22(m,2H),5.39(s,1H),5.32(s,2H),5.12(s,2H),4.43(s,2H),3.07−2.94(m,1H),2.18−2.07(m,2H),1.88−1.68(m,4H),1.63−1.51(m,2H)
1H NMR(300MHz,CDCl3)δ 8.36(s,1H),7.86−7.75(m,1H),7.53−7.46(m,1H),7.44−7.39(m,10H),7.15−7.07(m,1H),6.87(s,1H),6.82−6.73(m,1H),5.35(s,2H),5.20−5.10(m,1H),5.10−5.02(m,1H),4.97−4.82(m,3H),4 .11−3.89(m,2H),3.06−2.90(m,1H),2.12−2.04(m,2H),1.88−1.48(m,8H)
MS(ESI+):[M+H]+ m/z 626.0
MS(ESI+):[M+H]+m/z 643.1
1H NMR(300MHz,CDCl3)δ 8.53(s,1H),8.37(s,1H),7.84−7.89(m,2H),7.33−7.47(m,6H),5.39(d,J=14.4 Hz,1H),5.38(s,2H),4.62(d,J=14.4 Hz,1H),2.70−2.80(m,1H),1.85−1.98(m,4H),1.74−1.82(m,1H),1.26−1.61(m,5H)
1H NMR(300MHz,CDCl3)δ 8.53(s,1H),8.37(s,1H),7.84−7.89(m,2H),7.33−7.47(m,6H),5.39(d,J=14.4 Hz,1H),5.38(s,2H),4.62(d,J=14.4 Hz,1H),2.70−2.80(m,1H),1.85−1.98(m,4H),1.74−1.82(m,1H),1.26−1.61(m,5H)
1H NMR(300MHz,CDCl3)δ 8.46(s,1H),8.32(s,1H),7.81−7.94(m,2H),7.38−7.49(m,6H),5.39(s,2H),5.17(d,J=15.6 Hz,1H),4.91−4.98(m,1H),4.66(d,J=15.6 Hz,1H),3.96−4.19(m,2H),2.68−2.78(m,1H),2.25−2.36(m,1H),1.26−2.00(m,11H)
1H NMR(300MHz,CDCl3)δ 8.83(s,1H),8.43(s,1H),7.65−7.75(m,2H),7.25−7.31(m,1H),5.18(d,J=14.7 Hz,1H),4.87−4.96(m,1H),4.80(d,J=14.7 Hz,1H),4.10−4.18(m,1H),3.96−4.05(m,1H),2.78−2.89(m,1H),2.12−2.21(m,1H),1.24−2.04(m,11H). HRMS(ESI+)m/z 643.1447[M+H]+
1H NMR(300MHz,CDCl3)δ 8.46(s,1H),8.31(s,1H),7.40−7.59(m,8H),5.14(d,J=15.3 Hz,1H),5.05(s,2H),4.88−4.95(m,1H),4.65(d,J=15.3 Hz,1H),3.86−4.19(m,2H),2.68−2.77(m,1H),2.24−2.35(m,1H),1.25−1.96(m,11H)
1H NMR(300MHz,CDCl3)δ 8.48(s,1H),8.33(s,1H),7.46−7.67(m,3H),5 .18(d,J=14.7 Hz,1H),4.90−4.99(m,1H),4.66(d,J=14.7 Hz,1H),3.96−4.22(m,2H),2.69−2.80(m,1H),2.27−2.38(m,1H),1.26−2.07(m,11H)
1H NMR(300MHz,CDCl3)δ 8.46(s,1H),8.32(s,1H),7.79−7.90(m,2H),7.47(dd,J=7.8,JHF=7.8 Hz,1H),5.17(d,J=15.0 Hz,1H),4.93−4.99(m,1H),4.66(d,J=15.0 Hz,1H),4.12−4.20(m,1H),3.93−4.08(m,4H),2.68−2.78(m,1H),2.26−2.36(m,1H),1.84−2.00(m,5H),1.74−1.82(m,1H),1.26−1.64(m,5H). HRMS(ESI+)m/z 657.1604[M+H]+
1H NMR(300MHz,CDCl3)δ 7.86(d,J=8.2 Hz,1H),7.43−7.32(m,12H),7.10(d,J=8.3 Hz,2H),6.74(d,J=8.2 Hz,1H),6.55(s,1H),5.37(s,2H),4.92(s,2H),4.86(s,2H),1.32(s,9H)
1H NMR(300MHz,CDCl3)δ 7.87(d,J=8.7 Hz,1H),7.49−7.26(m,14H),6.29−6.13(m,2H),5.34(s,2H),5.12(s,2H),4.45(s,1H),4.33(d,J=5.0 Hz,2H),1.36(s,9H)
1H NMR(300MHz,CDCl3)δ 7.88−7.76(m,1H),7.45−7.24(m,12H),7.08−6.96(m,2H),6.69−6.59(m,1H),6.50(s,1H),5.37(s,2H),5.13−5.01(m,1H),4.94−4.78(m,2H),4.74(s,2H),4.19−3.92(m,2H),2.09−1.70(m,2H),1.31(s,9H)
MS(ESI+):[M+H]+ m/z 613.0
1H NMR(300MHz,CDCl3)δ 7.86−7.68(m,2H),7.52−7.27(m,9H),6.75−6.63(m,1H),5.37(s,2H),4.82(s,1H),4.43(s,2H),1.38(s,9H)
1H NMR(300MHz,CDCl3)δ 7.87−7.74(m,2H),7.47−7.30(m,5H),7.27−7.23(m,2H),7.10−6.95(m,3H),5.36(s,2H),5.28(d,J=14.4 Hz,1H),5.13−4.94(m,1H),4.91−4.81(m,1H),4.35−4.20(m,1H),4.06−3.99(m,1H),2.48−2.24(m,1H),1.97−1.80(m,1H),1.27(s,9H)
MS(ESI+):[M+H]+ m/z 615.1
1H NMR(300MHz,CDCl3)δ 9.20−8.95(m,1H),7.69−7.53(m,1H),7.45−7.38(m,5H),7.35−7.25(m,3H),7.08−6.96(m,3H),5.28−5.15(m,1H),5.02(s,2H),4.88−4.79(m,1H),4.36−4.17(m,1H),4.18−3.98(m,2H),2.39−2.22(m,1H),2.02−1.87(m,1H),1.29(s,9H)
MS(ESI+):[M+H]+ m/z 630.1
1H NMR(300MHz,CDCl3)δ 8.43(s,1H),8.35(d,J=1.2 Hz,1H),7.8 1(d,J=8.1 Hz,1H),7.33−7.48(m,5H),6.94(d,J=1.8 Hz,1H),6.84(dd,J=1.8. 8.1 Hz,1H),5.23(d,J=12.6 Hz,1H),5.13(d,J=12.6 Hz,1H),5.04(d,J=15.3 Hz,1H),4.87−4.93(m,1H),4.76(d,J=15.3 Hz,1H),4.19(t,JHF=1.8 Hz.3H),3.87−4.05(m,5H),2.69−2.79(m,1H),2.04−2.15(m,1H),1.24−1.98(m,11H)
1H NMR(300MHz,CDCl3)δ 8.48(d,J=1.2 Hz,1H),8.36(d,J=1.2 Hz,1H),8.17(d,J=8.7 Hz,1H),7.43−7.47(m,5H),7.23(d,J=1.8 Hz,1H),6.97(dd,J=1.8,8.7 Hz,1H),5.38(d,J=11.4 Hz,1H),5.27(d,J=11.4 Hz,1H),5.06(d,J=15.3 Hz,1H),4.92−4.99(m,1H),4.81(d,J=15.3 Hz,1H),4.20(t,JHF=1.8 Hz.3H),3.96−4.20(m,2H),2.70−2.80(m,1H),2.17−2.25(m,1H),1.75−1.98(m,6H),1.26−1.64(m,5H)
1H NMR(300MHz,CDCl3)δ 8.67(s,1H),8.37(s,1H),7.68−7.79(m,1H),6.58−6.72(m,2H),4.81−5.14(m,3H),4.20(brs,3H),3.90−4.09(m,2H),2.71−2.83(m,1H),1.28−2.29(m,12H). HRMS(ESI+)m/z 653.1686[M+H]+
1H NMR(300MHz,CDCl3)δ 8.20(br,1H),8.13(d,J=1.8 Hz,1H),7.97(d,J=8.2 Hz,1H),7.56−7.47(m,1H),5.37(s,2H)
1H NMR(300MHz,CDCl3)δ 8.37(d,J=1.8 Hz,1H),7.91(d,J=8.2 Hz,1H),7.53−7.45(m,2H),7.42(d,J=8.2 Hz,1H),7.28−7.24(m,1H),5.30(m,2H),5.02(s,2H),2.60−2.43(m,1H),1.92−1.72(m,5H),1.49−1.29(m,5H)
1H NMR(300MHz,CDCl3)δ 8.43(s,1H),7.65(d,J=8.4,1H),7.56−7.46(m,1H),7.23(d,J=8.0,1H),6.75(d,J=8.4Hz,1H),6.56(s,1H),5.84(s,1H),5.14(s,2H),4.47(s,2H),2.62−2.42(m,1H),1.94−1.72(m,5H),1.51−1.28(m,5H)
MS(ESI+):[M+H]+ m/z 636.17
1H NMR(300MHz,CDCl3)δ 8.33(s,1H),8.24−8.16(m,1H),7.80(s,1H),7.50−7.36(m,6H),7.20−7.10(m,1H),6.95(d,J=2.2 Hz,1H),6.87−6.76(m,1H),5.24−5.15(m,1H),5.14−5.05(m,1H),4.99−4.83(m,3H),4.15−3.94(m,2H),2.93(s,3H),2.60−2.42(m,1H),2.21−2.12(m,1H),2.02− 1.93(m,1H),1.92−1.72(m,5H),1.51−1.27(m,5H)
MS(ESI+):[M+H]+ m/z 653.2
1H NMR(300MHz,CDCl3)δ 8.59(m,1H),8.51(d,J=8.8 Hz,1H),8.37−8.22(m,2H),5.48(s,2H),3.83−3.62(m,2H),1.08−0.92(m,2H),0.07− −0.03(m,9H)
1H NMR(300MHz,CDCl3)δ 8.17−8.04(m,2H),6.91−6.76(m,2H),5.41(s,2H),4.53−3.92(m,2H),3.78−3.60(m,2H),1.06−0.89(m,2H),−0.01(s,9H)
1H NMR(300MHz,CDCl3)δ 8.37(d,J=8.7 Hz,1H),8.18(m,2H),8.02(d,J=2.1 Hz,1H),7.75(dd,J=8.7,2.1 Hz,1H),5.45(s,2H),3.81−3.60(m,2H),1.07−0.91(m,2H),0.09− −0.03(m,9H)
1H NMR(300MHz,CDCl3)δ 8.40(d,J=2.3 Hz,1H),8.33(d,J=8.3 Hz,1H),8.18(s,1H),7.65(d,J=2.3 Hz,1H),7.55(d,J=8.3 Hz,1H),7.47−7.36(m,1H),7.36−7.27(m,1H),5.44(s,2H),5.10(s,2H),3.80−3.60(m,2H),2.67−2.45(m,1H),2.1−1.6(m,5H),1.55−1.15(m,5H),1.07−0.88(m,2H),0.02(s,9H)
1H NMR(300MHz,CDCl3)δ 8.46(d,J=2.2 Hz,1H),8.10(m,2H),7.58(dd,J=8.0,2.2 Hz,1H),7.32(d,J=8.0 Hz,1H),6.88(dd,J=8.8,2.3 Hz,1H),6.77(d,J=2.3 Hz,1H),5.89−5.69(br,1H),5.40(s,2H),4.56(s,2H),3.77−3.61(m,2H),2.66−2.46(m,1H),2.0−1.70(m,5H),1.58−1.14(m,5H),1.05−0.86(m,2H),0.07(s,9H)
1H NMR300MHz,CDCl3)δ 8.43−8.26(m,2H),8.18(s,1H),7.55(s,1H),7.42−7.10(m,3H),5.45(s,2H),5.21−4.90(m,3H),4.27−3.97(m,2H),3.84−3.51(m,2H),2.66−2.48(m,1H),2.48−2.27(m,1H),1.96−1.71(m,6H),1.54−1.13(m,5H),1.10−0.89(m,2H),0.03(s,9H)
HRMS(ESI+)m/z 648.1847[M+H]+
1H NMR(300MHz,CDCL3)δ 7.67(d,J=8.1 Hz,1H),7.09(d,J=2 .1 Hz,1H),6.88(dd,J=8.1,2.1 Hz,1H),5.07(s,2H),4.41(br,2H),3.74−3.53(m,2H),1.05−0.87(m,2H),0.09− −0.04(m,9H)
1H NMR(300MHz,CDCl3)δ 8.48(s,1H),8.21(d,J=2.0 Hz,1H),8.09(dd,J=8.2,2.0 Hz,1H),7.97(d,J=8.2 Hz,1H),5.13(s,2H),3.76−3.60(m,2H),1.08−0.88(m,2H),0.06− −0.04(m,9H)
1H NMR(300MHz,CDCl3)δ 8.39(d,J=2.3 Hz,1H),7.93(d,J=7.9 Hz,1H),7.83(s,1H),7.68(d,J=7.9 Hz,1H),7.53(dd,J=7.9,2.3 Hz,1H),7.36−7.21(m,1H),5.12(s,2H),5.05(s,2H),3.76−3.56(m,2H),1.99−1.71(m,5H),1.50−1.19(m,5H),1.08−0.83(m,2H),0.08− −0.05(m,9H)
1H NMR(300MHz,CDCl3)δ 8.35(s,1H),7.94(d,J=8.0 Hz,1H),7.75(d,J=2.0 Hz,1H),7.70−7.59(m,1H),7.52(dd,J=8.0,2.0 Hz,1H),7.27−7.15(m,1H),5.12(s,2H),5.07−4.88(m,3H),3.79−3.52(m,2H),2.61−2.46(m,1H),1.97−1.70(m,5H),1.50−1.30(m,5H),1.05−0.85(m,2H),0.02(s,9H)
1H NMR(300MHz,CDCl3)δ 8.33(m,1H),7.87(d,J=7.9 Hz,1H),7.79(d,J=1.8 Hz,1H),7.60(dd,J=7.9,1.8 Hz,1H),7.53(dd,J=8.1,2.3 Hz,1H),7.35−7.07(m,1H),5.17(s,2H),5.09−4.83(m,3H),4.13−3.93(m,2H),2.61−2.42(m,1H),2.42−2.21(m,1H),1.94−1.64(m,6H),1.54−1.29(m,5H)
HRMS(ESI+)m/z 649.1563[M+H]+
MS(ESI+)m/z 661.0[M+H]+
1H NMR(300MHz,CDCl3)δ 7.24−7.29(m,5H),6.95−7.06(m,1H),4.15(s,2H)
1H NMR(300MHz,CDCl3)δ 7.48−7.58(m,1H)
1H NMR(300MHz,CDCl3)δ 8.59(s,1H),8.33(s,1H),7.84(d,J=8.1 Hz,1H),7.31−7.43(m,10H),6.82−6.93(m,2H),5.36(s,2H),5.07−5.19(m,4H),4.54−4.64(m,1H),3.99−4.07(m,1H),3.69−3.77(m,1H),2.68−2.79(m,1H),1.26−2.13(m,21H)
1H NMR(300MHz,CDCl3)δ 8.45(s,1H),8.40(s,1H),7.84(d,J=8.1 Hz,1H),7.34−7.44(m,10H),7.21−7.28(m,1H),6.96(d,J=1.8 Hz,1H),6.84(dd,J=1.8,8.1Hz,1H),5.37(s,2H),5.22(d,J=12.9 Hz,1H),5.13(d,J=12.9 Hz,1H),5.01(d,J=15.3 Hz,1H),4.90−4.95(m,1H),4.79(d,J=15.3 Hz,1H),3.93−4.09(m,2H),2.74−2.84(m,1H),1.26−2.14(m,12H)
1H NMR(300MHz,CDCl3)δ 11.4(brs,1H,OH),8.88(s,1H),8.51(s,1H),7.71(d,J=7.5 Hz,1H),7.25−7.35(m,1H),6.64−6.72(m,2H),4.98−5.10(m,3H),4.00−4.19(m,2H),2.86−2.97(m,1H),2.22−2.33(m,1H),1.26−2.11(m,11H). HRMS(ESI+)m/z 623.1577[M+H]+
1H NMR(300MHz,CDCl3)δ 7.54(d,J=8.1 Hz,1H),6.89(dd,J=8.0,7.7 Hz,1H),5.30(s,2H),4.35(s,2H)
1H NMR(300MHz,CDCl3)δ 8.62−8.38(m,2H),7.87−7.71(m,1H),5.42(s,2H)
1H NMR(300MHz,CDCl3)δ 8.34(d,J=2.0 Hz,1H),7.68(d,J=8.0 Hz,1H),7.53(dd,J=8.0,2.0 Hz,1H),7.46−7.39(m,1H),7.32(d,J=8.0 Hz,1H),5.50−5.37(m,3H),4.58(d,J=14.5 Hz,1H),2.61−2.47(m,1H),1.95−1.75(m,5H),1.53−1.28(m,5H)
1H NMR(300MHz,CDCl3)δ 8.47(d,J=2.0 Hz,1H),7.59−7.51(m,2H),7.24(d,J=8.0 Hz,1H),6.82(dd,J=7.8 Hz,7.7 Hz,1H),5.79(s,1H),5.29(s,2H),4.53(m,2H),2.63−2.48(m,1H),1.97−1.78(m,5H),1.51−1.25(m,5H)
MS(ESI+):[M+H]+ m/z 654.3
1H NMR(300MHz,CDCl3)δ 10.15(s,1H),7.85(d,J=2.3 Hz,1H),7.73(dd,J=8.5,2.3 Hz,1H),7.49(d,J=8.5 Hz,1H),3.21(s,6H)
1H NMR(300MHz,CDCl3)δ 7.91(dd,J=8.2,2.0 Hz,1H),7.85(d,J=2.0 Hz,1H),7.45(d,J=8.2 Hz,1H),7.43−7.34(m,5H),5.23(s,2H),3.13(s,3H),2.85(s,3H)
1H NMR(300MHz,CDCl3)δ 7.44−7.30(m,5H),7.09(d,J=8.0 Hz,1H),6.28(dd,J=8.0,2.0 Hz,1H),6.24(d,J=2.0 Hz,1H),5.03(s,2H),3.47(br s,2H),3.07(s,3H),2.88(s,3H)
1H NMR(300MHz,CDCl3)δ 8.78(s,1H),7.43−7.31(m,6H),7.18(d,J=8.1 Hz,1H),6.95(dd,J=8.1,1.9 Hz,1H),5.04(s,2H),3.12(s,3H),2.86(s,3H)
1H NMR(300MHz,CDCl3)δ 8.39−8.35(m,1H),7.50−7.43(m,1H),7.37−7.26(m,5H),7.26−7.20(m,1H),7.19−7.12(m,1H),6.92−6.85(m,2H),4.97(s,4H),3.07(s,3H),2.79(s,3H),2.58−2.43(m,1H),1.70−1.70(m 5H),1.45−1.30(m,5H)
1H NMR(300MHz,CDCl3)δ 8.42(m,1H),7.47(m,1H),7.40−7.25(m,5H),7.20(m,1H),7.12(m,1H),6.33−6.22(m,2H),5.15−4.98(m,3H),4.38(s,2H),3.06(s,3H),2.87(s,3H),2.60− 2.46(m,1H),1.92−1.73(m,5H),1.5 1−1.3 1(m,5H)
1H NMR(300MHz,CDCl3)δ 8.32(d,J=2.0 Hz,1H),7.47(dd,J=8.0,2.0 Hz,1H),7.42−7.29(m,5H),7.24(d,J=8.2 Hz,1H),7.14(d,J=8.0 Hz,1H),6.81−6.74(m,2H),5.15−4.82(m,5H),4.07−3.91(m,2H),3.10(s,3H),2.85(s,3H),2.58−2.43(m,1H),2.15−2.05(m,1H),1.80−1.68(m,6H),1.50−1.29(m,5H)
MS(ESI+):[M+H]+ m/z 667.4
1H NMR(300MHz,CDCl3)δ 8.49(s,1H),8.38(s,1H),7.86(d,J=8.1 Hz,1H),7.69−7.77(m,1H),7.33−7.44(m,10H),7.01−7.09(m,1H),6.95(d,J=1.8 Hz,1H),6.84(dd,J=1.8,8.1 Hz,1H),5.38(s,2H),5.21(d,J=12.6 Hz,1H),5.11(d,J=12.6 Hz,1H),5.00(d,J=15.3 Hz,1H),4.83−4.92(m,2H),3.94−4.02(m,1H),3.79−3.86(m,1H),2.73−2.83(m,1H),2.11−2.18(m,1H),1.26−1.99(m,11H)
1H NMR(300MHz,CDCl3)□11.14(brs,1H,OH),8.92(s,1H),8.49(s,1H),7.68−7.78(m,2H),7.05−7.14(m,1H),6.63−6.75(m,2H),5.09(s,2H),4.90−4.98(m,1H),4.01−4.10(m,1H),3.88−3.96(m,1H),2.86−2.98(m,1H),1.28−2.61(m,12H). MS(ESI+)m z 605.3[M+H]+
1H NMR(300MHz,CDCl3)δ12.46(s,1H),8.34(d,J=1.9 Hz,1H),7.5 1(dd,J=8.0,1.9 Hz,1H),7.46(d,J=8.4 Hz,1H),7.19(d,J=8.0 Hz,1H),6.76(d,J=2.0 Hz,1H),6.72(dd,J=8.4,2.1 Hz,1H),5.18−5.04(m,1H),4.98−4.79(m,2H),4.13−4.01(m,2H),2.58−2.45(m,1H),2.43−2.27(m,1H),2.22−2.08(m,1H),1.92−1.72(m,5H),1.49−1.31(m,5H). MS(ESI+):[M+H]+ m/z 639.4
1H NMR(300MHz,CDCl3)δ 2.43(t,JHF= 2.1 Hz.3H)
1H NMR(300MHz,CDCl3)δ 8.44(s,1H),8.38(s,1H),7.84(d,J=8.1 Hz,1H),7.34−7.44(m,10H),6.97(s,1H),6.83(d,J=8.1 Hz,1H),5.37(s,2H),5.22(d,J=12.9 Hz,1H),5 .12(d,J=12.9 Hz,1H),5.03(d,J=15.0 Hz,1H),4.88−4.95(m,1H),4.78(d,J=15.0 Hz,1H),3.93−4.05(m,2H),2.73−2.84(m,1H),1.28−2.34(m,15H)
1H NMR(300MHz,CDCl3)δ 11.17(brs,1H,OH), 8.88(s,1H),8.47(s,1H),7.71(d,J=8.1Hz,1H),6.70(d,J=8.1Hz,1H),6.64(s,1H),5.11(d,J=14.1Hz,1H),4.97−5.02(m,2H),3.97−4.18(m,2H),2.83−2.94(m,1H),2.23−2.40(m,4H),1.26−2.07(m,11H)。HRMS(ESI+)m/z637.1739[M+H]+
1H NMR(300MHz,CDCl3)δ 8.50(s,1H),8.46(s,2H),8.38(s,1H),8.06(s,1H),7.87(d,J=8.4 Hz,1H),7.34−7.44(m,10H),6.98(d,J=1.8 Hz,1H),6.87(dd,J=1.8,8.4 Hz,1H),5.38(s,2H),5.22(d,J=12.6 Hz,1H),5.06−5.14(m,2H),4.93−4.99(m,1H),4.83(d,J=15.3 Hz,1H),3.92−3.99(m,1H),3.56−3.63(m,1H),2.72−2.83(m,1H),1.26−2.16(m,12H)
1H NMR(300MHz,CDCl3)δ 11.20(brs,1H,OH),8.97(s,1H),8.47(s,3H),8.10(s,1H),7.72(d,J=8.4 Hz,1H),6.70(d,J=8.4 Hz,1H),6.65(s,1H),5.19(d,J=12.3 Hz,1H),4.97−5.08(m,2H),3.98−4.07(m,1H),3.66−3.74(m,1H),2.85−2.97(m,1H),2.26−2.36(m,1H),1.26−2.08(m,11H). HRMS(ESI+)m/z 687.1691[M+H]+
19F NMR(282 MHz,CDCl3)δ −134.1,−135.4
1H NMR(300MHz,CDCl3)δ 8.43(s,1H),8.40(s,1H),7.84(d,J=8.1 Hz,1H),7.34−7.44(m,10H),6.94(s,1H),6.83(d,J=8.1 Hz,1H),5.38(s,2H),5.22(d,J=12.6 Hz,1H),5.14(d,J=12.6 Hz,1H),5.01(d,J=15.6 Hz,1H),4.90−4.95(m,1H),4.79(d,J=15.6 Hz,1H),3.91−4.10(m,2H),2.74−2.85(m,1H),1.26−2.83(m,12H)
1H NMR(300MHz,CDCl3)δ 11.13(brs,1H,OH),8.84(s,1H),8.49(s,1H),7.72(d,J=7.5 Hz,1H),6.64−6.72(m,2H),4.98−5.1 1(m,3H),4.11−4.20(m,1H),4.00−4.08(m,1H),2.85−2.97(m,1H),2.22−2.33(m,1H),1.26−2.13(m,11H). HRMS(ESI+)m/z 657.1190 [M+H]+
1H NMR(300MHz,CDCl3)δ 8.68(s,1H),8.62(s,1H),7.89(d,J=8.1 Hz,1H),7.55−7.63(m,2H),7.34−7.45(m,10H),7.08(s,1H),6.90(d,J=8.1 Hz,1H),5.39(s,2H),5.27(d,J=12.3 Hz,1H),5.14−5.20(m,2H),4.98(d,J=15.9 Hz,1H),4.84−4.89(m,1H),3.79−3.87(m,1H),3.54−3.62(m,1H),2.98−3.08(m,1H),1.26−2.45(m,12H)
1H NMR(300MHz,CDC13)□11.19(brs,1H,OH),9.01(s,1H),8.54(s,1H),7.75(d,J=8.4 Hz,1H),7.56−7.62(m,2H),6.67−6.74(m,2H),5.27(d,J=14.7 Hz,1H),5.05(d,J=14.7 Hz,1H),4.85−4.90(m,1H),3.84−3.92(m,1H),3.65−3.73(m,1H),2.89−3.00(m,1H),2.31−2.43(m,1H),1.26−2.09(m,11H). MS(ESI+)m/z 603.3[M+H]+
1H NMR(300MHz,CDCl3)δ 9.46(s,1H),8.47(s,1H),8.02(d,J=8.9 Hz,1H),7.47(d,J=8.9,1H),5.99(s,2H),3.59(t,J= 8.4 Hz,2H),0.91(t,J= 8.4 Hz,2H),−0.06(s,9H)
1H NMR(300MHz,CDCl3)δ 8.38(s,1H),8.06(d,J=8.8 Hz,1H),7.66(s,1H),7.51(d,J=8.0 Hz,1H),7.34−7.24(m,2H),5.95(s,2H),5.07(s,2H),3.55(t,J= 8.4 Hz,2H),2.59−2.43(m,1H),1.88−1.72(m,5H),1.49−1.29(m,5H),0.92−0.82(t,J= 8.4 Hz,2H),−0.08(s,9H)
1H NMR(300MHz,CDCl3)δ 8.43(d,J=2.1 Hz,1H),7.75(d,J=9.0 Hz,1H),7.48(dd,J=8.0,2.1 Hz,1H),7.23(d,J=8.0 Hz,1H),6.82(dd,J=9.0,1.9 Hz,1H),6.55(d,J=1.9 Hz,1H),5.81(s,2H),5.50(s,1H),4.44(s,2H),3.60−3.47(m,2H),2.61−2.44(m,1H),1.89−1.70(m,5H),1.47−1.29(m,5H),0.92−0.79(m,2H),−0.09(s,9H)
1H NMR(300MHz,CDCl3)δ 8.32(d,J=2.0 Hz,1H),8.05(d,J=8.7 Hz,1H),7.60(s,1H),7.50(dd,J=8.0,2.0 Hz,1H),7.25−7.18(m,2H),5.94(s,2H),5.02−4.92(m,3H),4.09−4.01(m,2H),3.64−3.52(m,2H),2.56−2.42(m,1H),2.40−2.27(m,1H),2.00−1.69(m,6H),1.50−1.24(m,5H),0.96−0.80(m,2H),−0.06(s,9H)
MS(ESI+): [M+H]+ m/z 621.3
1H NMR(300MHz,CDCl3)δ5 9.71(s,1H),8.42(d,J=1.7Hz,1H),7.84(dd,J=8.9,1.7 Hz,1H),7.70(d,J=8.9 Hz,1H),5.98(s,2H),3.57(t,J=8.2 Hz,2H),0.89(t,J= 8.2 Hz,2H),−0.08(s,9H)
1H NMR(300MHz,CDCl3)δ 8.52(s,1H),8.43(s,1H),8.04(s,1H),7.72(d,J=8.7 Hz,1H),7.49(d,J=8.7 Hz,1H),6.00(s,2H),5.08(s,2H),3.66−3.52(m,2H),2.83−2.68(m,1H),2.00−1.71(m,5H),1.63−1.32(m,5H),0.96−0.84(m,2H),−0.07(s,9H)
1H NMR(300MHz,CDCl3)δ 8.56(d,J=1.3 Hz,1H),8.42(d,J=1.3 Hz,1H),7.47(d,J=8.7 Hz,1H),7.10−6.99(m,2H),5.89(s,2H),4.51(s,2H),3.59−3.48(m,2H),2.81−2.67(m,1H),1.97−1.77(m,5H),1.64−1.31(m,5H),0.93−0.83(m,2H),−0.07(s,9H)
1H NMR(300MHz,CDCl3)δ 8.43(d,J=1.2 Hz,1H),8.37(d,J=1.2 Hz,1H),7.92(s,1H),7.75(d,J=8.7 Hz,1H),7.48(d,J=8.7 Hz,1H),5.99(s,2H),5.15(d,J=15.3 Hz,1H),4.99−4.90(m,1H),4.79(d,J=15.3 Hz,1H),4.08−3.95(m,2H),3.64−3.57(m,2H),2.79−2.65(m,1H),2.41−2.27(m,1H),1.98−1.76(m,6H),1.63−1.30(m,5H),0.98−0.86(m,2H),−0.05(s,9H)
MS(ESI+):[M+H]+ m/z 622.3
1H NMR(300MHz,CDCl3)δ 8.55(s,1H),8.48(s,1H),7 .85(d,J=8.1 Hz,1H),7.33−7.45(m,10H),6.99(d,J=1.8 Hz,1H),6.85(dd,J=1.8,8.1 Hz,1H),6.73−6.81(m,2H),5.38(s,2H),5.24(d,J=12.6 Hz,1H),5.14(d,J=12.6 Hz,1H),4.99(d,J=15.9 Hz,1H),4.88−4.95(m,2H),3.97−4.05(m,1H),3.87−3.94(m,1H),2 .87−2.97(m,1H),1.26−2.38(m,12H)
1H NMR(300MHz,CDCl3)δ 11.13(brs,1H,OH),8.90(s,1H),8.52(s,1H),7.70(d,J=8.7 Hz,1H),6.76−6.84(m,2H),6.65−6.70(m,2H),5.15(d,J=14.7 Hz,1H),4.96−5.04(m,2H),4.06−4.13(m,1H),3.93−4.01(m,1H),2.89−3.01(m,1H),2.24−2.35(m,1H),1.26−2.10(m,11H). MS(ESI+)m/z 605.3 [M+H]+
1H NMR(300MHz,CDCl3)δ 8.45(s,1H),8.36(s,1H),8.27(d,J=8.5 Hz,1H),8.14(s,1H),7.64(d,J=1.6 Hz,1H),7.38(dd,J=8.5,1.6 Hz,1H),5.37(s,2H),4.98(s,2H),3.63−3.49(m,2H),2.69−2.53(m,1H),1.85−1.55(m,5H),1.51−1.18(m,5H),0.93−0.77(m,2H),−0. 13(s,9H)
1H NMR(300MHz,CDCl3)δ8.56(s,1H),8.46(s,1H),8.17−8.07(m,2H),6.92−6.85(m 1H),6.8 1(m,1H),5.51−5.38(m,3H),4.59(s,2H),3.75−3.62(m,2H),2.85−2.71(m,1H),2.00−1.77(m,5H),1.52−1.24(m,5H),1.03−0.92(m,2H),0.00(s,9H)
1H NMR(300MHz,CDCl3)δ 8.44(s,1H),8.39−8.33(m,2H),8.18(s,1H),7.61(d,J=1.6 Hz,1H),7.42(dd,J=8.5,1.6 Hz,1H),5.44(s,2H),5.17−5.01(m,2H),4.86(d,J=15.5 Hz,1H),4.18−3.99(m,2H),3.75−3.65(m,2H),2.80−2.66(m,1H),2.45−2.25(m,1H),1.98−1.67(m,6H),1.63−1.34(m,5H),1.02−0.95(m,2H),0.02(s,9H)
MS(ESI+):[M+H]+ m/z 649.2
1H NMR(300MHz,CDCl3)δ 7.20−7.39(m,1H),6.72−6.81(m,1H),4.04(s,2H)
19F NMR(282 MHz,CDCl3)δ −109.8,−117.8,−128.2,−156.7
1H NMR(300MHz,CDCl3)δ 8.44(s,1H),8.40(s,1H),7.84(d,J=8.1 Hz,1H),7.34−7.44(m,10H),6.94(d,J=1.5 Hz,1H),6.83(dd,J=1.5,8.1 Hz,1H),5.38(s,2H),5.22(d,J=12.3 Hz,1H),5.13(d,J=12.3 Hz,1H),5.02(d,J=15.3 Hz,1H),4.89−4.94(m,1H),4.78(d,J=15.3 Hz,1H),4.01−4.09(m,1H),3.91−3.98(m,1H),2.74−2.85(m,1H),1.26−2.13(m,12H)
1H NMR(300MHz,CDCl3)δ 11.09(brs,1H,OH),8.83(s,1H),8.50(s,1H),7.73(d,J=8.4 Hz,1H),6.66−6.72(m,2H),4.97−5.09(m,3H),4.10−4.19(m,1H),3.99−4.07(m,1H),2.87−2.96(m,1H),1.26−2.45(m,12H). MS(ESI+)m/z 657.2[M+H]+
HRMS(ESI+)m/z 654.1919[M+H]+
1H NMR(300MHz,CDCl3)δ2.32−2.34(m,3H)
1H NMR(300MHz,CDCl3)δ 8.47(s,1H),8.40(s,1H),7.84(d,J=8.1 Hz,1H),7.33−7.44(m,10H),6.96(d,J=1.8 Hz,1H),6.83(d,J=1.8,8.1 Hz,1H),5.37(s,2H),5.22(d,J=12.6 Hz,1H),5.12(d,J=12.6 Hz,1H),5.03(d,J=15.3 Hz,1H),4 .88−4.95(m,1H),4.81(d,J=15.3 Hz,1H),3.88−4.06(m,2H),2.74−2.85(m,1H),2.22(s,3H),1.26−2.15(m,12H)
1H NMR(300MHz,CDCl3)δ 11.11(brs,1H,OH),8.88(s,1H),8.49(s,1H),7.71(d,J=8.7 Hz,1H),6.65−6.71(m,2H),5.10(d,J=14.1 Hz,1H),4.96−5.05(m,2H),4.06−4.15(m,1H),3.95−4.02(m,1H),2.86−2.96(m,1H),2.26(s,3H),1.26−2.09(m,12H). HRMS(ESI+)m/z 637. 1726 [M+H]+
1H NMR(300MHz,CDCl3)δ7.02−7.11(m,1H)
1H NMR(300MHz,CDCl3)δ 8.45(s,1H),8.39(s,1H),7.84(d,J=8.1 Hz,1H),7.33−7.44(m,10H),6.81−6.95(m,3H),5.37(s,2H),5.22(d,J=12.6 Hz,1H),5.12(d,J=12.6 Hz,1H),4.89−5.00(m,2H),4.83(d,J=15.3 Hz,1H),3.99−4.07(m,1H),3.88−3.95(m,1H),2.74−2.84(m,1H),1.26−2.20(m,12H)
1H NMR(300MHz,CDCl3)δ 11.10(brs,1H,OH),8.50(s,1H),8.49(s,1H),7.72(d,J=7.5 Hz,1H),6.88−6.97(m,1H),6.65−6.71(m,2H),4.98−5.11(m,3H),4.09−4.18(m,1H),3.96−4.04(m,1H),2.85−2.98(m,1H),1.26−2.32(m,12H). HRMS(ESI+)m/z 623.1584[M+H]+
1H NMR(300MHz,CDCl3)δ 8.12(d,J=2.1 Hz,1H),7.64(ddd,J=2.1,8.4,8.4 Hz,1H),7.18−7.33(m,5H),6.82(dd,J=3.0,8.4 Hz,1H),4.04(s,2H)
1H NMR(300MHz,CDCl3)δ 8.96(d,J=2.1 Hz,1H),8.45(ddd,J=2.1,6.6,9.0 Hz,1H),7.23(dd,J=9.0,3.0 Hz,1H)
1H NMR(300MHz,CDCl3)δ 8.73(d,J=1.8 Hz,1H),8.50(s,1H),8.34−8.38(m,2H),7.86(d,J=8.7 Hz,1H),7.32−7.42(m,10H),7.04(dd,J=3.0,9.0 Hz,1H),6.97(s,1H),6.86(d,J=8.7 Hz,1H),5.38(s,2H),5.21(d,J=12.3 Hz,1H),5.03−5.13(m,2H),4.82−4.93(m,2H),3.86−3.94(m,1H),3.54−3.60(m,1H),2.71−2.82(m,1H),1.26−2.40(m,12H)
1H NMR(300MHz,CDCl3)δ 11.19(brs,1H,OH),8.94(s,1H),8.74(d,J=2.4 Hz,1H),8.47(s,1H),8.37−8.43(m,1H),7.73(d,J=8.4 Hz,1H),7.10(dd,J=2.4,8.4 Hz,1H),6.70(d,J=8.1 Hz,1H),6.66(s,1H),5.16(d,J=14.7 Hz,1H),4.92−5.03(m,2H),3.94−4.02(m,1H),3.63−3.70(m,1H),2.84−2.92(m,1H),1.25−2.38(m,12H). HRMS(ESI+)m/z 570.1820 [M+H]+
1H NMR(300MHz,CDCl3)δ 7.86−7.88(m,1H),7.22−7.48(m,6H),4.08(s,2H)
1H NMR(300MHz,CDCl3)δ 8.73(s,1H),8.19−8.25(m,1H)
1H NMR(300MHz,CDCl3)δ 8.48−8.50(m,2H),8.40(d,J=1.2 Hz,1H),8.23−8.29(m,1H),7.84(d,J=8.1 Hz,1H),7.30−7.44(m,10H),6.96(d,J=1.8 Hz,1H),6.86(dd,J=1.8,8.1 Hz,1H),5.38(s,2H),5.21(d,J=12.3 Hz,1H),5.04−5.14(m,2H),4.91−4.96(m,1H),4.86(d,J=15.9 Hz,1H),3.90−3.98(m,1H),3.54−3.61(m,1H),2.74−2.84(m,1H),2.05−2.15(m,1H),1.85−2.00(m,5H),1.75−1.82(m,1H),1.26−1.66(m,5H)
1H NMR(300MHz,CDCl3)δ 11.14(brs,1H,OH),8.94(s,1H),8.51(s,1H),8.47(s,1H),8.23−8.29(m,1H),7.74(d,J=8.4 Hz,1H),6.67−6.71(m,2H),5.18(d,J=14.1 Hz,1H),4.95−5.02(m,2H),3.96−4.05(m,1H),3.64−3.71(m,1H),2.82−2.92(m,1H),2.26−2.37(m,1H),1.26−2.07(m,11H).
MS(ESI+):[M+H]+m/z 588.3
リガンド構造を描画し、MarvinSketch(ChemAxon)で3次元座標に変換した。次に、Avogadro(Hanwell MD,et al.(2012)J. Cheminformatics 4:17)において、MMFF94力場(Halgren TA(1996) J. Comput.Chem.17:490-519)を使用して、エネルギーの構造を最小化した。インシリコでAlaに変異したK591を有するStat3モノマー(PDB 1bg1)の構造は、UCSFキメラでのドッキングのために調製した(Pettersen EF,et al.,(2004)J. Comput. Chem. 25:1605-1612)。K591A変異体は、K591を確実にモデル化することが困難であるために使用した。これは柔軟性があり、推定リガンド結合部位にまで及ぶ。リガンドは、Yasara(Krieger E,et al.,(2014)Bioinformatics 30:2981-2982)を使用した代替側鎖立体構造を持つStat3の5つの構造に対してドッキングした。これは、Autodock Vina(Trott O,et al.,J. Comput. Chem. 31:455-461)に基づいたドッキングおよびスコアリングアルゴリズムを使用する。マニュアル検査は、化学的に最も合理的でSARデータと整合性があるYasaraの最高スコアモデルをサポートした。次に、残基591をLysに戻し、SCWRL回転異性体ライブラリ(Shapovalov MV,et al.,(2007)Proteins 66:279-303)を使用して、Yasaraのドッキングモデルに適合するように側鎖回転異性体を最適化した。最終モデルは、YasaraでNova力場(Krieger E. et al.,(2002)Proteins 47:393-402; Krieger E,et al.,(2009)Proteins 77 Suppl 9:114-122)を使用してエネルギーを最小化した。二次元のリガンド相互作用図は、シュレディンガーマエストロで作成した。
核抽出物の調製とDNA結合活性/電気泳動移動度シフトアッセイ(EMSA)は、前述のように実行した(Zhang X,et al.,(2010)Biochem Pharmacol 79:1398-409; Zhang X,et al.,(2012) Proc Natl Acad Sci USA 109:9623-8)。使用した32P標識オリゴヌクレオチドプローブは、Stat1およびStat3に結合するhSIE(c−fos遺伝子からの高親和性sis誘導性要素、m67バリアント、5'−AGCTTCATTTCCCGTAAATCCCTA)(配列番号1)、およびStat1およびStat5結合用のMGFe((ウシb−カゼイン遺伝子プロモーター、5'−AGATTTCTAGGAATTCAAの乳腺因子要素)(配列番号2)であった。示されている場合を除き、核抽出物を化合物と室温で30分間プレインキュベートした後、EMSA分析に供する前に放射標識プローブと30℃で30分間インキュベートした。必要に応じて、Stat3:DNA複合体に対応するバンドをスキャンし、ImageJを使用して化合物の各濃度について定量化し、IC50値が得られた化合物の濃度に対するコントロールの割合(DMSO)としてプロットした。
選択した類似体は、Stat3とStat5の両方のDNA結合活性を破壊するが、in vitroでのStatlのそれは破壊しない。
透過性、およびヒトおよびマウスの肝臓ミクロソーム研究は、Eurofins Cerep PanlabsおよびEurofin Discovery Servicesによって実施された。
(論考)
Claims (32)
- 式I、
式中、R1はアリールまたは5または6員ヘテロアリールから選択され、ヘテロ原子は1つ以上のO、N、S(A)2であり、Sは硫黄であり、Aは酸素または電子対から選択され、アリールまたは5または6員ヘテロアリールは、ハロ、CF3、C1−C6アルキル、C1−C6分岐アルキル、アリール、ヘテロアリール、C3−C7シクロアルキル、C3−C7シクロアルケニル、3−6員の複素環、3−7員の飽和複素環、縮合C2−C5アルキレンで任意に置換される、ここで、1つ以上のCH2基をO、NR9、S(A)2で置き換えることができ、Sは硫黄であり、Aは酸素または電子対から選択される、アリールまたは5または6員ヘテロアリールは任意に置換されてよいナフタレン、任意に置換されてよいインドール、ベンゾフラン、ベンゾチオフェンであり、
R2およびR3は独立してHまたはC1−C6アルキルから選択され;
ここで、R2およびR3はC3−C6シクロアルカン環を形成することができ、このC3−C6シクロアルカン環は、1つ以上のC1−C6アルキル、ヒドロキシル、NR9R10、またはC1−C6アルコキシで置換することができ、
R4は、H、C1−C6アルキル、(CH2)fNR9R10、(CH2)fOR9、(CH2)fCO2R9、(CH2)fCO2NR9R10から選択され、
R5は、C1−C6アルキル、(CH2)fNR9R10、(CH2)fOR9、(CH2)fCO2R9、(CH2)fCO2NR9R10から選択される。ここで、R4とR5は、C3−C6シクロアルカン環を形成でき、このC3−C6シクロアルカン環は1つ以上のC1−C6アルキル、ヒドロキシル、NR9R10、またはC1−C6アルコキシで置換でき、1つ以上のCH2基をO、NR9、S(A)2で置換でき、Sは硫黄であり、Aは酸素または電子対から選択され、
R6はC1−C6アルキルから選択されるものであり、
ここで、R4およびR6はC3−C6シクロアルカン環を形成することができ、このC3−C6シクロアルカン環は1つ以上のC1−C6アルキル、ヒドロキシル、NR9R10で置換でき、1つ以上のCH2基はO、NR9、S(A)2で置換でき、Sは硫黄、Aは酸素または電子対から選択でき、式中、R4およびR6は、任意に置換されたピロール環を形成でき、前記ピロール環の1つ以上のCH基は、O、N、S(A)2で置き換えることができ、Sは硫黄であり、Aは酸素または電子対から選択されものであり、
R7はCF3、アリールまたはヘテロアリール基から選択され、アリールまたはヘテロアリール基はC1−C6アルキル、ハロ、ヒドロキシル、CN、またはCF3から選択される1〜5個の置換基で置換されており、
R8は、1以上のH、C1−C6アルキル、C1−C6アルコキシ、ヒドロキシル、ハロゲン、OC(O)CH3、NR9R10、CN、CF3、CO2R9、CO2NR9R10、(CH2)fNR9R10、(CH2)fOR9、または(CH2)fCO2R9から選択される置換基であり; R9はHまたはC1−C6アルキルから選択され; R10はH、C1−C6アルキルから選択され、
Wは、CO2H、テトラゾール、ベンジル、C(0)NHOR10およびCF2OHから選択され、
QはC、CH、N、O、Sでであり、ここで、QとR8は複素環を形成でき、
pは0または1から選択され、yは0または1から選択され、
fは0〜4から選択され、tは0または1から選択される、
で表される化合物、
および、その溶媒和物、水和物、または薬学的に許容される塩。 - 式II、
ここで、アリールまたはヘテロアリールは、ヒドロキシル、カルボン酸、カルボキシレート、ベンゾヒドロキサム酸、ヒドロキシル置換アルキルのうちの1つまたは複数で置換され得るものであり、
およびその溶媒和物、水和物、または薬学的に許容される塩。 - 式III、
式中、R11はアリールまたはヘテロアリールから選択され、
ここで、アリールまたはヘテロアリールは、1つまたは複数のヒドロキシル、カルボン酸、カルボン酸塩、ベンゾヒドロキサム酸、ニトロソ、アルキルカルボン酸、C1−C6アルキル、およびハロで置換されるものであり、
式中、R12は(R)−CH(CH3)である、
で表される、請求項1に記載の化合物、
およびその溶媒和物、水和物、または薬学的に許容される塩。 - R11が
から選択される、請求項3に記載の化合物、およびその塩。 - 式IV、
式中、R15は置換アリールから選択され、置換はヒドロキシ、カロボキシル酸、およびベンゾヒドロキサム酸の1つまたは複数であり、
式中、R16は(R)−CH(CH3)であり、
式中、YはCHおよびNから選択される、
で表される請求項1に記載の化合物、およびその溶媒和物、水和物、または薬学的に許容される塩。 - R14が、
- R15が
- 式V、
R18は水素およびハロから選択され、
R19は水素およびヒドロキシルから選択され、
R20は−OH、−NHOH、および −(O−,Na+)から選択され;
R21はCH3である、
で表される請求項1に記載の化合物、およびその溶媒和物、水和物、または薬学的に許容される塩。 - 式VI、
式中、nは1〜3から選択され、
XはCHおよびNから選択され、
R17はCH2およびOから選択され、
R18は水素およびハロから選択され、
R19は水素およびヒドロキシルから選択され、
R20は−OH、NHOH、および−(O−,Na+)から選択される、
で表される、請求項1に記載の化合物およびその溶媒和物、水和物、または薬学的に許容される塩。 - 化合物、
から選択される請求項1に記載の化合物、およびその溶媒和物、水和物、または薬学的に許容される塩。 - 化合物、
から選択される請求項1に記載の化合物、およびその溶媒和物、水和物、または薬学的に許容される塩。 - 式VIII、
式中、W,X,Y,およびZはそれぞれ独立してCHまたはNを含むか、除外することができ、
R21は、置換されていてもよいアリール、置換されていてもよいヘテロアリール、または複素環と縮合した置換されていてもよいアリールから選択され、
置換アリールまたは置換ヘテロアリールまたは複素環と縮合した置換アリールは、ヒドロキシル、カルボン酸、カルボキシレート、ヒドロキサム酸、アミド、アルキルアミド、ジアルキルアミド、アルコキシアミノ、アルキルカルボン酸、C1−C6アルキル、およびハロの1つまたは複数で置換することができ、
nは1から3から選択される、
から選択される、請求項1記載の化合物、およびその溶媒和物、水和物、または薬学的に許容される塩。 - R21が以下のいずれかの化合物、
から選択される請求項12に記載の化合物。 - 式VIII、
式中、W,X,Y,Z、およびQは、それぞれ独立して、CHまたはNを含むか、除外することができ、
dは0、1、2、3、または4から選択され、
R21は、置換されていてもよいアリール、置換されていてもよいヘテロアリール、または複素環と縮合した置換されていてもよいアリールから選択され、
R22はハロゲンである、
で表される請求項1に記載の化合物。 - R21が以下の部分
- ハロゲンがフッ素である請求項14に記載の化合物。
- 請求項1〜16のいずれか1項に記載の治療有効量の化合物、塩、結晶または多形体、および薬学的に許容される賦形剤を含む医薬組成物。
- 請求項1〜16のいずれか1項に記載の化合物の治療有効量を含む、構成的に活性化されたStat3を有する腫瘍細胞を選択的に治療するのに使用する組成物。
- 癌、過形成、または新形成からなる群から選択される状態の治療のための薬剤の調製のための、請求項1〜16のいずれか1項に記載の化合物の使用。
- 腫瘍進行が阻害または低減されるか、またはMDRが阻害または低減されることを特徴とする請求項19に記載の使用。
- 癌を治療する方法であって、それを必要とする対象に治療有効量の請求項18に記載の組成物を投与することを含む方法。
- 請求項21に記載の組成物を対象に投与する方法であって、異常に活性なStat3を有する細胞の生存、成長または移動が阻害される方法。
- 組成物の有効用量が約0.05mg/kg〜約5g/kgの範囲である請求項21記載の方法。
- 組成物の有効用量が、約0.05mg/kg〜約5g/kgの1つまたは複数の用量で与えられる請求項21に記載の方法。
- 組成物の有効用量が約.08mg/kg〜約0.5mg/kg、約.08〜約0.24mg/kg、または約0.24〜約0.5mg/kg、または約0.08〜0.5mg/kgである請求項21に記載の方法。
- 組成物の1つまたは複数の有効用量が経口投与される請求項21に記載の方法。
- 組成物の1つまたは複数の有効用量が皮下、静脈内、または筋肉内に投与される請求項21に記載の方法。
- 癌が固形腫瘍である請求項21に記載の方法。
- 固形腫瘍が神経膠腫、乳癌または膵臓癌を含む請求項21に記載の方法。
- 癌が、肺、乳房、前立腺、膵臓、卵巣、膀胱、頭頸部、甲状腺、脳、皮膚および腎臓からなる群より選択される請求項21に記載の方法。
- 前記癌が、脳腫瘍、神経膠腫、髄芽腫、脳血管腫、乳房、前立腺、膵臓、卵巣、膀胱、頭頸部、悪性黒色腫、多発性骨髄腫、リンパ腫、未分化大T細胞リンパ腫、セザリー症候群、EBV関連バーキットリンパ腫、HSVサイミリ依存性(T細胞)、皮膚T細胞リンパ腫、菌状息肉腫、HTLV−I依存性白血病を含む白血病、赤白血病、急性リンパ性白血病(ALL)、慢性リンパ性白血病(CLL)、急性骨髄性白血病(AML)、慢性骨髄性白血病(CML)、巨核球性白血病、および大顆粒リンパ球(LGL)白血病、または甲状腺、皮膚、肺、腎臓がん、腎細胞がん、膵臓がん腺癌、卵巣癌、頭頸部の有棘細胞癌、またはホジキンリンパ腫からなる群より選択される請求項21に記載の方法。
- 前記組成物の各用量が約0.08mg/kgから約0.5mg/kg未満であり、前記用量が経口、皮内、筋肉内、腹腔内、静脈内、局所、皮下、および硬膜外経路からなる群から選択される送達経路により投与される請求項21に記載の方法。
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