JP6909155B2 - Cns障害を処置するための組成物および方法 - Google Patents
Cns障害を処置するための組成物および方法 Download PDFInfo
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- JP6909155B2 JP6909155B2 JP2017520471A JP2017520471A JP6909155B2 JP 6909155 B2 JP6909155 B2 JP 6909155B2 JP 2017520471 A JP2017520471 A JP 2017520471A JP 2017520471 A JP2017520471 A JP 2017520471A JP 6909155 B2 JP6909155 B2 JP 6909155B2
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- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Substances C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 1
- 239000003174 triple reuptake inhibitor Substances 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 210000001260 vocal cord Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
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- 230000037221 weight management Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
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- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group
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- C07J1/0003—Androstane derivatives
- C07J1/0018—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa
- C07J1/0022—Androstane derivatives substituted in position 17 beta, not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
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- C07J13/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having a carbon-to-carbon double bond from or to position 17
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- C07J3/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by one carbon atom
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- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
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- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0066—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by a carbon atom forming part of an amide group
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- C07—ORGANIC CHEMISTRY
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- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0053—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa not substituted in position 16
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
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- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/0015—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa
- C07J7/002—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group not substituted in position 17 alfa not substituted in position 16
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- C07J7/0065—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by an OH group free esterified or etherified
- C07J7/007—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by an OH group free esterified or etherified not substituted in position 17 alfa
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- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
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- C07J71/001—Oxiranes
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Description
本願は、米国仮出願第62/064,961号(2014年10月16日出願)に対する優先権を主張する。この米国仮出願の全内容は、本明細書中に参考として援用される。
脳の興奮性は、昏睡状態から痙攣に及ぶ連続である動物の覚醒レベルと定義され、様々な神経伝達物質によって制御されている。一般に、神経伝達物質は、ニューロン膜を横断するイオンのコンダクタンスの制御に関与する。安静時、ニューロン膜は、およそ−70mVという電位(または膜電圧)を有し、細胞内部は、細胞外部に対して負である。電位(電圧)は、ニューロン半透膜を横断するイオン(K+、Na+、Cl−、有機アニオン)バランスの結果である。神経伝達物質は、前シナプス小胞に貯蔵され、ニューロン性活動電位の影響下において放出される。シナプス間隙へ放出されると、アセチルコリンなどの興奮性の化学伝達物質は、膜の脱分極(−70mVから−50mVへの電位の変化)を引き起こす。この作用は、Na+イオンに対する膜透過性を高めるアセチルコリンによって刺激されるシナプス後ニコチン性レセプターにより媒介される。低下した膜電位は、シナプス後活動電位の形でニューロンの興奮性を刺激する。
例えば、GABA調節因子として作用するように設計されたC21置換神経刺激性ステロイドが本明細書中で提供される。特定の実施形態において、このような化合物は、被験体において麻酔および/または鎮静を誘導するための治療剤として有用であると想定される。いくつかの実施形態において、このような化合物は、必要とする被験体(例えば、レット症候群、脆弱X症候群、またはアンジェルマン症候群を有する被験体)においてCNS関連障害(例えば、睡眠障害、気分障害、例えばうつ病、統合失調症スペクトラム障害、痙攣障害、記憶および/または認知の障害、運動障害、人格障害、自閉症スペクトラム障害、疼痛、外傷性脳損傷、脈管疾患、物質乱用障害および/または離脱症候群、あるいは耳鳴)を処置するための治療剤として有用であることが想定される。
1つの実施形態において、R2、R3a、R4aまたはR4bのうちの少なくとも1個は、水素ではない。例えば、1つの実施形態において、R2、R3a、R4aまたはR4bのうちの少なくとも2個は、水素ではない。
式(I−a)において:R6は、置換もしくは非置換のC1〜6アルキル、置換もしくは非置換のC2〜6アルケニル、置換もしくは非置換のC2〜6アルキニル、置換もしくは非置換のC3〜6カルボシクリル、C1〜6ハロアルキル、ハロゲン、シアノ、−ORA6、−C(=O)ORA6、−SRB6、−S(=O)RB6、またはS(=O)2RB6であり、ここでRA6は、水素または置換もしくは非置換のC1〜6アルキル、置換もしくは非置換のC2〜6アルケニル、置換もしくは非置換のC2〜6アルキニル、置換もしくは非置換のC3〜6カルボシクリル、またはC1〜6ハロアルキルであり、そしてRB6は、置換もしくは非置換のC1〜6アルキルまたは置換もしくは非置換のC3〜6カルボシクリルであり;そしてnは、0、1、2、または3である。
式(I)のステロイド、その下位の属、およびその薬学的に受容可能な塩は、本明細書中でまとめて、「本発明の化合物」と称される。
化学的定義
特定の官能基および化学的用語の定義を下記で詳細に説明する。化学元素は、元素周期表(CASバージョン,Handbook of Chemistry and Physics,第75版,内表紙)に従って特定され、特定の官能基は、一般に、その中に記載されているとおりに定義される。さらに、有機化学の通則、ならびに特定の官能性部分および反応性は、Thomas Sorrell,Organic Chemistry,University Science Books,Sausalito,1999;SmithおよびMarch,March’s Advanced Organic Chemistry,第5版,John Wiley & Sons,Inc.,New York,2001;Larock,Comprehensive Organic Transformations,VCH Publishers,Inc.,New York,1989;およびCarruthers,Some Modern Methods of Organic Synthesis,第3版,Cambridge University Press,Cambridge,1987に記載されている。
Raaの各存在は、独立して、C1〜10アルキル、C1〜10ペルハロアルキル、C2〜10アルケニル、C2〜10アルキニル、C3〜10カルボシクリル、3〜14員ヘテロシクリル、C6〜14アリールおよび5〜14員ヘテロアリールから選択されるか、または2つのRaa基が連結して、3〜14員ヘテロシクリルもしくは5〜14員ヘテロアリール環を形成し、ここで、各アルキル、アルケニル、アルキニル、カルボシクリル、ヘテロシクリル、アリールおよびヘテロアリールは、独立して、0、1、2、3、4または5個のRdd基で置換され;
Rbbの各存在は、独立して、水素、−OH、−ORaa、−N(Rcc)2、−CN、−C(=O)Raa、−C(=O)N(Rcc)2、−CO2Raa、−SO2Raa、−C(=NRcc)ORaa、−C(=NRcc)N(Rcc)2、−SO2N(Rcc)2、−SO2Rcc、−SO2ORcc、−SORaa、−C(=S)N(Rcc)2、−C(=O)SRcc、−C(=S)SRcc、−P(=O)2Raa、−P(=O)(Raa)2、−P(=O)2N(Rcc)2、−P(=O)(NRcc)2、C1〜10アルキル、C1〜10ペルハロアルキル、C2〜10アルケニル、C2〜10アルキニル、C3〜10カルボシクリル、3〜14員ヘテロシクリル、C6〜14アリールおよび5〜14員ヘテロアリールから選択されるか、または2つのRbb基が連結して、3〜14員ヘテロシクリルもしくは5〜14員ヘテロアリール環を形成し、ここで、各アルキル、アルケニル、アルキニル、カルボシクリル、ヘテロシクリル、アリールおよびヘテロアリールは、独立して、0、1、2、3、4または5個のRdd基で置換され;
Rccの各存在は、独立して、水素、C1〜10アルキル、C1〜10ペルハロアルキル、C2〜10アルケニル、C2〜10アルキニル、C3〜10カルボシクリル、3〜14員ヘテロシクリル、C6〜14アリールおよび5〜14員ヘテロアリールから選択されるか、または2つのRcc基が連結して、3〜14員ヘテロシクリルもしくは5〜14員ヘテロアリール環を形成し、ここで、各アルキル、アルケニル、アルキニル、カルボシクリル、ヘテロシクリル、アリールおよびヘテロアリールは、独立して、0、1、2、3、4または5個のRdd基で置換され;
Rddの各存在は、独立して、ハロゲン、−CN、−NO2、−N3、−SO2H、−SO3H、−OH、−ORee、−ON(Rff)2、−N(Rff)2、−N(Rff)3 +X−、−N(ORee)Rff、−SH、−SRee、−SSRee、−C(=O)Ree、−CO2H、−CO2Ree、−OC(=O)Ree、−OCO2Ree、−C(=O)N(Rff)2、−OC(=O)N(Rff)2、−NRffC(=O)Ree、−NRffCO2Ree、−NRffC(=O)N(Rff)2、−C(=NRff)ORee、−OC(=NRff)Ree、−OC(=NRff)ORee、−C(=NRff)N(Rff)2、−OC(=NRff)N(Rff)2、−NRffC(=NRff)N(Rff)2、−NRffSO2Ree、−SO2N(Rff)2、−SO2Ree、−SO2ORee、−OSO2Ree、−S(=O)Ree、−Si(Ree)3、−OSi(Ree)3、−C(=S)N(Rff)2、−C(=O)SRee、−C(=S)SRee、−SC(=S)SRee、−P(=O)2Ree、−P(=O)(Ree)2、−OP(=O)(Ree)2、−OP(=O)(ORee)2、C1〜6アルキル、C1〜6ペルハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜10カルボシクリル、3〜10員ヘテロシクリル、C6〜10アリール、5〜10員ヘテロアリールから選択され、ここで、各アルキル、アルケニル、アルキニル、カルボシクリル、ヘテロシクリル、アリールおよびヘテロアリールは、独立して、0、1、2、3、4もしくは5個のRgg基で置換され;
Reeの各存在は、独立して、C1〜6アルキル、C1〜6ペルハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜10カルボシクリル、C6〜10アリール、3〜10員ヘテロシクリルおよび3〜10員ヘテロアリールから選択され、ここで、各アルキル、アルケニル、アルキニル、カルボシクリル、ヘテロシクリル、アリールおよびヘテロアリールは、独立して、0、1、2、3、4または5個のRgg基で置換され;
Rffの各存在は、独立して、水素、C1〜6アルキル、C1〜6ペルハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜10カルボシクリル、3〜10員ヘテロシクリル、C6〜10アリールおよび5〜10員ヘテロアリールから選択されるか、または2つのRff基が連結して、3〜14員ヘテロシクリルもしくは5〜14員ヘテロアリール環を形成し、ここで、各アルキル、アルケニル、アルキニル、カルボシクリル、ヘテロシクリル、アリールおよびヘテロアリールは、独立して、0、1、2、3、4または5個のRgg基で置換され;
Rggの各存在は、独立して、ハロゲン、−CN、−NO2、−N3、−SO2H、−SO3H、−OH、−OC1〜6アルキル、−ON(C1〜6アルキル)2、−N(C1〜6アルキル)2、−N(C1〜6アルキル)3 +X−、−NH(C1〜6アルキル)2 +X−、−NH2(C1〜6アルキル)+X−、−NH3 +X−、−N(OC1〜6アルキル)(C1〜6アルキル)、−N(OH)(C1〜6アルキル)、−NH(OH)、−SH、−SC1〜6アルキル、−SS(C1〜6アルキル)、−C(=O)(C1〜6アルキル)、−CO2H、−CO2(C1〜6アルキル)、−OC(=O)(C1〜6アルキル)、−OCO2(C1〜6アルキル)、−C(=O)NH2、−C(=O)N(C1〜6アルキル)2、−OC(=O)NH(C1〜6アルキル)、−NHC(=O)(C1〜6アルキル)、−N(C1〜6アルキル)C(=O)(C1〜6アルキル)、−NHCO2(C1〜6アルキル)、−NHC(=O)N(C1〜6アルキル)2、−NHC(=O)NH(C1〜6アルキル)、−NHC(=O)NH2、−C(=NH)O(C1〜6アルキル)、−OC(=NH)(C1〜6アルキル)、−OC(=NH)OC1〜6アルキル、−C(=NH)N(C1〜6アルキル)2、−C(=NH)NH(C1〜6アルキル)、−C(=NH)NH2、−OC(=NH)N(C1〜6アルキル)2、−OC(NH)NH(C1〜6アルキル)、−OC(NH)NH2、−NHC(NH)N(C1〜6アルキル)2、−NHC(=NH)NH2、−NHSO2(C1〜6アルキル)、−SO2N(C1〜6アルキル)2、−SO2NH(C1〜6アルキル)、−SO2NH2、−SO2C1〜6アルキル、−SO2OC1〜6アルキル、−OSO2C1〜6アルキル、−SOC1〜6アルキル、−Si(C1〜6アルキル)3、−OSi(C1〜6アルキル)3 −C(=S)N(C1〜6アルキル)2、C(=S)NH(C1〜6アルキル)、C(=S)NH2、−C(=O)S(C1〜6アルキル)、−C(=S)SC1〜6アルキル、−SC(=S)SC1〜6アルキル、−P(=O)2(C1〜6アルキル)、−P(=O)(C1〜6アルキル)2、−OP(=O)(C1〜6アルキル)2、−OP(=O)(OC1〜6アルキル)2、C1〜6アルキル、C1〜6ペルハロアルキル、C2〜6アルケニル、C2〜6アルキニル、C3〜10カルボシクリル、C6〜10アリール、3〜10員ヘテロシクリル、5〜10員ヘテロアリールであり;ここで、X−は、対イオンである。
本明細書中で使用される場合、用語「調節」とは、GABAレセプター機能の阻害または相乗作用のことを指す。「調節因子」(例えば、調節因子化合物)は、例えば、GABAレセプターのアゴニスト、部分アゴニスト、アンタゴニスト、または部分アンタゴニストであり得る。
本明細書中に一般に記載されるように、本発明は、例えば、GABA調節因子として作用するように設計されたC21置換神経刺激性ステロイドを提供する。特定の実施形態において、このような化合物は、被験体において麻酔および/または鎮静を誘導するための治療剤として有用であると想定される。特定の実施形態において、このような化合物は、CNS関連障害を処置するための治療剤として有用であると想定される。
1つの局面において、式(I):
薬学的組成物
使用および処置の方法
本明細書中に記載される化合物は、本明細書中に記載される方法において、例えば神経変性疾患などの本明細書中に記載される障害の処置において使用され得る。
本明細書中に記載される化合物は、本明細書中に記載される方法において、例えば気分障害などの本明細書中に記載される障害の処置において使用され得る。
本明細書中に記載される化合物は、本明細書中に記載される方法において、例えば不安障害などの本明細書中に記載される障害の処置において使用され得る。
摂食障害
本明細書中に記載される化合物は、本明細書中に記載される方法において、例えば国際公開第2013/112605号および国際公開第2014/031792号(これらの内容は、その全体が参照により本明細書中に援用される)に記載されているようなてんかん、てんかん発作重積状態、または発作などの本明細書中に記載される障害の処置において使用され得る。
てんかん発作重積状態(SE)
発作
本明細書中に記載される化合物は、本明細書中に記載される方法において、例えば振顫などの本明細書中に記載される障害の処置において使用され得る。
本明細書中に記載される化合物は、本明細書中に記載される方法において、例えば麻酔または鎮静を誘導するために使用され得る。麻酔とは、健忘症、痛覚脱失、反応性の喪失、骨格筋反射の喪失、低下したストレス応答、またはこれらすべての同時の、薬理学的に誘導される可逆的状態である。これらの影響は、影響の正しい組み合わせを単独で提供する1個の薬物から得られ得るか、または時々、結果の非常に特殊な組み合わせを達成するために、薬物(例えば、催眠薬、鎮静薬、麻痺薬、鎮痛薬)の組み合わせを用いて得られ得る。麻酔は、患者が外科手術および他の手順を、麻酔を受けなければ経験するであろう困難および疼痛を経験せずに、行うことを可能にする。
鎮静および痛覚脱失は、最小の鎮静(不安緩解)から全身麻酔までに及ぶ、連続した意識の状態を包含する。
等価物および範囲
材料および方法
実施例1。1の合成。
1H NMR: (400 MHz, CDCl3) δ 4.02-3.90 (m, 1H), 3.75 (t, J=4.4Hz, 4H), 3.48-3.30 (m, 4H), 3.20-3.18 (m, 2H), 2.61-2.40 (m, 5H), 2.22-2.08 (m, 1H), 1.92-1.78 (m, 3H), 1.73-1.48 (m, 6H), 1.40-1.15 (m, 9H), 0.99-0.88 (m, 4H), 0.80-0.68 (m, 1H), 0.61 (s, 3H).
1H NMR (2): (400 MHz, CDCl3) δ 7.68 (s, 2H), 5.32-5.15 (m, 2H), 4.01-3.91 (m, 1H), 3.41-3.29 (m, 4H), 2.62-2.50 (m, 1H), 2.28-2.14 (m, 1H), 2.13-2.04 (m, 1H), 1.95-1.88 (m, 1H), 1.88-1.62 (m, 5H), 1.56-1.19 (m, 11H), 1.02-0.95 (m, 1H), 0.93 (s, 3H), 0.81-0.72 (m, 1H), 0.69 (s, 3H).
1H NMR (3): (400 MHz, CDCl3) δ 7.75 (s, 1H), 7.64 (s, 1H), 5.32-5.09 (m, 2H), 4.01-3.91 (m, 1H), 3.41-3.29 (m, 4H), 2.70-2.58 (m, 1H), 2.28-2.14 (m, 1H), 2.12-2.04 (m, 1H), 1.95-1.88 (m, 1H), 1.88-1.62 (m, 5H), 1.56-1.20 (m, 11H), 1.03-0.95 (m, 1H), 0.93 (s, 3H), 0.81-0.72 (m, 1H), 0.66 (s, 3H).
1H NMR (A3): (400 MHz, CDCl3) δ 5.11-5.02 (m, 1H), 4.39-4.35 (m, 1H), 4.07-4.02 (m, 1H), 2.41-2.32 (m, 2H), 2.21-2.09 (m, 2H), 1.91-1.71 (m, 4H), 1.70-1.57 (m, 8H), 1.57-1.42 (m, 4H), 1.41-1.29 (m, 3H), 1.11-1.06 (m, 4H), 1.06-1.04 (m, 3H), 1.01-0.93 (m, 2H), 0.89-0.81 (m, 1H).
1H NMR (A4) : (400 MHz, CDCl3) δ 5.10-5.03 (m, 1H), 4.40-4.37 (m, 1H), 4.88-4.84 (m, 1H), 4.44-4.31 (m, 2H), 2.20-2.09 (m, 1H), 1.89-1.72 (m, 4H), 1.69-1.63 (m, 4H), 1.61-1.48 (m, 7H), 1.43-1.11 (m, 6H), 1.11-1.04 (m, 4H), 1.04-0.94 (m, 5H), 0.90-0.81 (m, 12H), 0.2 (s, 6H).
1H NMR (A5) : (400 MHz, CDCl3) δ 5.11-5.02 (m, 1H), 3.99-3.96 (m, 1H), 3.23-3.17 (m, 1H), 3.28 (s, 3H), 2.73-2.67 (m, 1H), 2.46-2.32 (m, 1H), 2.23-2.11 (m, 1H), 1.88-1.74 (m, 2H), 1.71-1.64 (m, 4H), 1.63-1.61 (m, 4H), 1.51-1.33 (m, 5H), 1.22-1.08 (m, 5H), 1.04 (s, 3H), 0.96 (s, 3H), 0.94-0.88 (m, 11H), 0.87-0.78 (m, 2H), 0.2 (s, 6H).
1H NMR (A6) : (400 MHz, CDCl3) δ 3.97-3.93 (m, 1H), 3.89-3.81 (m, 1H), 3.75-3.64 (m, 1H), 3.64-3.61 (m, 1H), 3.21 (s, 3H), 2.34 -2.27 (m, 1H),0.96-0.92 (m, 4H), 0.87 (s, 9H), 0.81 (s, 3H), 0.78-0.72 (m, 1H), 0.2 (m, 6H).
1H NMR (A7) : (400 MHz, CDCl3) δ 3.98-3.93 (m, 1H), 3.71-3.68 (m, 1H), 3.21 (s, 3H), 2.54-2.36 (m, 4H), 2.21-2.06 (m, 5H), 1.96-1.31 (m, 20H), 1.30-1.06 (m, 8H), 1.02-0.91 (m, 4H), 0.92-0.84 (m, 10H), 0.83-0.72 (m, 5H), 0.2 (m, 6H).
1H NMR (A8) : (400 MHz, CDCl3) δ 4.07-4.02 (m, 1H), 3.71-3.68 (m, 1H), 3.21 (s, 3H), 2.49-2.41 (m, 2H), 2.19-2.08 (m, 4H), 1.74-1.57 (m, 8H), 1.56-1.49 (m, 3H), 1.48-1.40 (m, 3H), 1.38-1.32 (m, 1H), 1.31-1.16 (m, 5H), 1.16-1.03 (m, 1H), 0.97 (s, 3H), 0.84-0.78 (m, 1H), 0.77 (s, 3H).
1H NMR (A9) : (400 MHz, CDCl3) δ 4.08-4.04 (m, 1H), 3.91 (s, 2H), 3.71-3.68 (m, 1H), 3.28-3.19 (m, 3H), 2.77-2.71 (m, 1H), 2.51-2.35 (m, 2H), 2.34-2.24 (m, 1H), 2.22-2.11 (m, 1H), 1.83-1.68 (m, 7H), 1.67-1.48 (m, 10H), 1.47-1.38 (m, 2H), 1.21-1.10 (m, 4H), 0.98 (s, 3H), 0.77-0.86 (m, 4H).
1H NMR (4) : (400 MHz, CDCl3) δ 7.78-7.70 (m, 2H), 5.28-5.26 (m, 2H), 4.10-4.03 (m, 1H), 3.73-3.68 (m, 4H), 3.26 (s, 3H), 2.48-2.57 (m, 1H), 2.23-2.12 (m, 1H), 1.78-1.69 (m, 4H), 1.47-1.42 (m, 2H), 1.41-1.07 (m, 8H), 1.04-0.93 (m, 4H), 0.93-0.82 (m, 5H).
1H NMR (5) : (400 MHz, CDCl3) δ 7.79 (s, 3H), 7.69 (s, 3H), 5.38-5.27 (d, J=17.6Hz, 1H), 5.19-5.11 (d, J=18Hz, 1H), 4.12-4.06 (m, 1H), 3.81-3.68 (m, 1H), 3.24 (s, 3H), 2.67-2.52 (m, 2H), 2.31-2.26 (m, 1H), 1.89-1.68 (m, 5H), 1.52-1.38 (m, 2H), 1.46-1.14 (m, 9H), 0.98 (s, 3H), 0.93-0.78 (m, 7H).
1HNMR (A11): (400MHz, CDCl3) δ 5.32-5.18 (m, 1H), 3.98-3.88 (m, 1H), 3.79-3.70 (m, 1H), 3.42-3.33 (m, 2H), 2.88-2.82 (m, 1H), 2.78-2.72 (m, 1H), 2.60-2.51 (m, 1H), 2.48-2.28 (m, 2H), 1.94-1.68 (m, 6H), 1.64-1.60 (m, 3H), 1.58-1.38 (m, 2H), 1.38-1.24 (m, 4H), 1.24-1.16 (m, 7H), 1.16-1.12 (m, 1H), 0.84 (s, 3H).
1HNMR (A12): (400MHz, CDCl3) δ 5.18-5.16 (m, 1H), 3.84-3.78 (m, 1H), 3.75-3.68 (m, 1H), 3.38-3.28 (m, 1H), 3.28-3.22 (m, 1H), 2.85-2.78 (m, 1H), 2.74-2.66 (m, 1H), 2.60-2.55 (m, 1H), 2.48-2.24 (m, 2H), 1.85-1.65 (m, 5H), 1.61-1.54 (m, 5H), 1.36-1.22 (m, 3H), 1.31-1.10 (m, 8H), 0.89-0.86 (m, 10H), 0.81 (s, 3H), 0.03 (s, 6H).
1HNMR (A13): (400MHz, CDCl3) δ 4.34-4.26 (m, 1H), 3.86-3.80 (m, 1H), 3..73-3.64 (m, 1H), 3.60-3.51 (m, 1H), 3.46-3.35 (m, 1H), 3.34-3.30 (m, 1H), 1.96-1.83 (m, 2H), 1.83-1.65 (m, 4H), 1.41-1.30 (m, 3H), 1.30-1.21 (m, 7H), 1.19-1.10 (m, 9H), 1.10-0.94 (m, 3H), 0.86 (s, 12H), 0.78-0.73 (m, 1H), 0.03 (s, 6H).
1H NMR (A14) (400 MHz, CDCl3) δ 3.87-3.80 (m, 1H), 3.75-3.68 (m, 1H), 3.40-3.26 (m, 2H), 2.78-2.70 (m, 2H), 2.58-2.46 (m, 2H), 2.31-2.15 (m, 2H), 2.20 (s, 3H), 1.86-1.66 (m, 6H), 1.40-1.05 (m, 13H), 0.95-0.84 (m, 9H), 0.59 (s, 3H), 0.05 (s, 3H).
1H NMR (A15) (400 MHz, CDCl3) δ 3.96-3.88 (m, 1H), 3.78-3.70 (m, 1H), 3.42-3.34 (m, 2H), 2.76-2.68 (m, 2H), 2.60-2.45 (m, 2H), 2.30-2.18 (m, 1H), 2.12 (s, 3H), 1.92-1.73 (m, 8H), 1.61-1.50 (m, 2H), 1.38-1.25 (m, 9H), 1.25-1.14 (m, 10H), 0.93 (s, 3H), 0.59 (s, 3H).
1H NMR (A16) (400 MHz, CDCl3) δ 3.96-3.88 (m, 1H), 3.78-3.74 (m, 2H), 3.76-3.68 (m, 1H), 3.39-3.33 (m, 2H), 3.12-3.06 (m, 1H), 2.66-2.60 (m, 1H), 2.51-2.44 (m, 2H), 2.25-2.18 (m, 1H), 1.98-1.76 (m, 7H), 1.41-1.24 (m, 6H), 1.23-1.12 (m, 8H), 0.63 (s, 3H).
1H NMR(6)(400 MHz, CDCl3) δ 7.71 (s, 2H), 5.21-5.20 (m, 2H), 3.95-3.90 (m, 1H), 3.80-3.70 (m, 1H), 3.42-3.33 (m, 2H), 2.78-2.70 (m, 2H), 2.63-2.58 (m, 1H), 2.40-2.35 (m, 1H), 1.90-1.70 (m, 7H), 1.43-1.25 (m, 7H), 1.24-1.13 (m, 8H), 0.69 (s, 3H).
1H NMR(7)(400 MHz, CDCl3) δ 7.79 (s, 1H), 7.65 (s, 1H), 5.26-5.10 (m, 2H), 3.98-3.90 (m, 1H), 3.80-3.70 (m, 1H), 3.40-3.35 (m, 2H), 2.85-2.80 (m, 1H), 2.75-2.65 (m, 1H), 2.60-2.45 (m, 2H), 2.31-2.20 (m, 1H), 1.98-1.78 (m, 7H), 1.46-1.25 (m, 7H), 1.24-1.13 (m, 7H), 0.68 (s, 3H).
1H NMR(A19): (400 MHz, CDCl3) δ 4.74-4.61 (m, 1H), 4.39-4.36 (m, 1H), 4.35-3.31 (m, 1H), 4.22-4.15 (m, 2H), 3.29-3.22 (m, 1H), 3.16-3.05 (m, 1H), 2.77-2.58 (m, 1H), 2.54-2.36 (m, 3H), 2.38-2.13 (m, 8H), 1.15 (s, 3H), 0.88 (s, 3H).
1H NMR (8): (400 MHz, CDCl3) δ 7.74-7.62 (m, 2H), 5.32-5.18 (m, 2H), 4.47-4.38 (m, 1H), 4.12-4.03 (m, 2H), 2.57-2.45 (m, 1H), 2.33-2.15 (m, 2H), 1.91-1.63 (m, 6H), 1.55-1.45 (m, 2H), 1.42-1.09 (m, 7H), 1.11-1.05 (m, 1H), 1.03 (s, 3H), 0.96 (s, 3H), 0.94-0.82 (m, 1H).
1H NMR (9): (400 MHz, CDCl3) δ 7.78 (s, 1H), 7.68 (s, 1H), 5.31-5.25 (d, J=17.6Hz, 1H), 5.20-5.14 (d, J=17.6Hz, 1H), 4.48-4.45 (m, 1H), 4.12-4.03 (m, 1H), 2.65-2.53 (m, 2H), 2.32-2.15 (m, 1H), 1.92-1.71 (m, 5H), 1.68-1.59 (m, 4H), 1.54-1.42 (m, 1H), 1.41-1.15 (m, 4H), 1.13-1.05 (m, 1H), 1.04 (s, 3H), 0.94-0.85 (m, 4H).
1H NMR (A25) (400 MHz, CDCl3) δ 2.54-2.52 (m, 1H), 2.13-2.10 (m, 4H), 1.98-1.63 (m, 4H), 1.49-1.30 (m, 8H), 1.25-1.00 (m, 12H), 0.91 (s, 3H), 0.90-0.85 (m, 1H), 0.58 (s, 3H).
1H NMR (A26) (400 MHz, CDCl3) δ 3.94-3.87 (m, 2H), 2.83-2.79 (m, 1H), 2.18-2.16 (m, 1H), 1.94-1.71 (m, 6H), 1.57-1.47 (m, 8H), 1.26-1.10 (m, 11H), 0.93 (s, 3H), 0.61 (s, 3H).
1H NMR (10) (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.80 (s, 1H), 5.03-4.87 (m, 2H), 2.25-2.15 (m, 1H), 2.10-1.80 (m, 3H), 1.75-1.71 (m, 3H), 1.54-1.35 (m, 8H), 1.33-0.95 (m, 10H), 0.94 (s, 3H), 0.64 (s, 3H). LCMS tR=1.268min(2分間のクロマトグラフィー)、10−80AB、C26H37N3O2Na[M+Na]+のMS ESI計算値446、実測値446。
1H NMR (11): (400 MHz, CDCl3) δ 7.89-7.86 (dd, J1 = 2.8 Hz, J2 = 6.4 Hz, 2H), 5.52-5.47 (m, 2H), 2.66-2.62 (t, J = 8.8 Hz, 1H), 2.21-2.16 (m, 2H), 1.95-1.73 (m, 7H), 1.55-1.27 (m, 14H), 1.22-1.08 (m, 2H), 0.94 (s, 3H), 0.73 (s, 3H). LCMS tR=1.512min(2分間のクロマトグラフィー)、10−80AB、C28H40N3O2[M+H]+のMS ESI計算値450、実測値432([M+H−18].
1H NMR( 12): (400 MHz, CDCl3) δ 8.09-8.07 (d, J = 8.4 Hz, 1H), 7.51-7.40 (m, 1H), 7.38-7.32 (m, 2H), 5.41-5.40 (m, 2H), 2.72-2.70 (m, 1H), 2.20-2.17 (m, 2H), 1.96-1.74 (m, 7H), 1.45-1.23 (m, 14H), 1.22-1.08 (m, 2H), 0.96 (s, 3H), 0.71 (s, 3H). LCMS Rt=1.438min(2分間のクロマトグラフィー)、10−80AB、C28H40N3O2[M+H]+のMS ESI計算値450、実測値450.
1H NMR (13): (400 MHz, CDCl3) δ 7.41 (s, 1H), 5.13-5.12 (m, 2H), 2.57-2.52 (m, 1H), 2.32 (s, 3H), 2.25-2.15 (m, 1H), 2.10-2.00 (m, 1H), 1.94-1.59 (m, 5H), 1.52-1.40 (m, 9H), 1.26-1.06 (m, 10H), 0.94 (s, 3H), 0.67 (s, 3H). LCMS Rt=0.93min(1.5分間のクロマトグラフィー)、5−95AB、C25H40N3O2[M+H]+のMS ESI計算値414、実測値414.
1H NMR (14): (400 MHz, CDCl3) δ 7.73-7.71 (m, 1H), 7.07-7.05 (m, 2H), 5.43-5.42 (m, 2H), 3.87 (s, 3H), 2.64-2.62 (m, 1H), 2.25-2.12 (m, 2H), 1.95-1.63 (m, 5H), 1.53-1.48 (m, 8H), 1.44-1.26 (s, 8H), 1.24-1.06 (m, 2H), 0.95 (s, 3H), 0.71(s, 3H). LCMS Rt=0.993min(1.5分間のクロマトグラフィー)、5−95AB、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
1H NMR (15): (400 MHz, CDCl3) δ 7.38 (s, 1H), 7.21-7.19 (m, 1H), 7.15-7.13 (m, 1H), 5.36-5.35 (m, 2H), 3.88 (s, 3H), 2.67-2.65 (m, 1H), 2.25-2.10 (m, 2H), 1.95-1.63 (m, 5H), 1.52-1.44 (m, 8H), 1.43-1.26 (m, 8H), 1.22-1.08 (m, 2H), 0.95 (s, 3H), 0.69 (s, 3H). LCMS Rt=0.944min(1.5分間のクロマトグラフィー)、5−95AB、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
1H NMR (16): (400 MHz, CDCl3) δ 7.92-7.90 (d, J = 9.6 Hz, 1H), 7.02-6.99 (dd, J1 = 2.8 Hz, J2 = 9.6 Hz, 1H), 5.38-5.27 (m, 2H), 3.88 (s, 3H), 2.70-2.68 (m, 1H), 2.25-2.10 (m, 2H), 1.95-1.62 (m, 5H), 1.54-1.45 (m, 9H), 1.43-1.26 (m, 8H), 1.22-1.08 (m, 2H), 0.95 (s, 3H), 0.71 (s, 3H). LCMS Rt=0.939min(1.5分間のクロマトグラフィー)、5−95AB、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
1HNMR (17): (400 MHz, CDCl3) δ 7.67 (d, J=9.2Hz, 1H), 7.35-7.27 (m, 1H), 7.06-7.02 (m, 1H), 5.59-5.50 (m, 2H), 2.67 (d, J=4Hz, 1H), 2.22-1.74 (m, 8H), 1.59-1.44 (m, 8H), 1.27-1.12 (m, 10H), 0.97 (s, 3H), 0.74 (s, 3H). LCMS Rt=0.992min(1.5分間のクロマトグラフィー)、5−95AB、C28H39FN3O2[M+H]+のMS ESI計算値468、実測値450[M+H−18].
1HNMR (18): (400 MHz, CDCl3) δ 7.45-7.41 (m, 1H), 7.10 (d, J=8Hz, 1H) 7.04 (t, J=8Hz ,1H), 5.47-5.37 (m, 2H), 2.70 (t, J=12Hz, 1H), 2.21-1.74 (m, 10H), 1.56-1.44 (m, 5H), 1.27-1.09 (m, 11H),0.96 (s, 3H),0.70 (s, 3H). LCMS Rt=1.402min(2分間のクロマトグラフィー)、10−80AB、C28H39FN3O2[M+H]+のMS ESI計算値468、実測値468.
1H NMR (19): (400 MHz, CDCl3) δ 7.46 (s, 1H), 6.58 (d, J=2Hz, 1H) ,5.02-4.91 (m, 2H), 2.59 (d, J=8Hz, 1H), 2.06-1.72 (m, 7H), 1.59-1.42 (m, 8H), 1.27-1.07 (m, 10H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS Rt=2.667min(3分間のクロマトグラフィー)、10−80AB、C26H38F3N2O2[M+H]+のMS ESI計算値467、実測値449[M+H−18].
1H NMR (20): (400 MHz, CDCl3) δ 7.49 (s, 1H), 6.60 (d, J=1.6Hz, 1H) ,5.05-4.91 (m, 2H), 2.75 (t, J=8Hz, 1H), 1.88-1.80 (m, 8H), 1.57-1.41 (m, 8H), 1.38-0.95 (m, 10H), 0.92 (d , J=8Hz ,6H). LCMS Rt=2.687min(3分間のクロマトグラフィー)、10−80AB、C26H38F3N2O2[M+H]+のMS ESI計算値467、実測値449[M+H−18].
1H NMR (21): (400 MHz, CDCl3) δ 7.86-7.84 (m,1H), 7.46 (d, J=8Hz, 1H) ,7.20 (t, J=20Hz, 1H) 5.49-5.44 (m, 2H), 2.64(t, J=16Hz, 1H), 2.21-1.74 (m, 8H), 1.56-1.43 (m, 7H), 1.33-0.96 (m, 10H),0.83 (s, 3H),0.73 (s, 3H). LCMS Rt=2.712min(3分間のクロマトグラフィー)、10−80AB、C28H39FN3O2[M+H]+のMS ESI計算値468、実測値450([M+H]+−18).
1H NMR (22): δ 8.05-8.02 (m, 1H), 7.16 (t,J=9.2Hz,1H), 6.99-6.96 (m, 1H), 5.43-5.31 (m, 2H), 2.72 (d, J=8.4Hz ,1H), 2.17-1.97 (m, 2H), 1.78-1.57 (m, 6H), 1.47-1.42 (m, 6H), 1.28-1.08 (m, 10H), 0.97 (s, 3H), 0.71 (s, 3H). LCMS Rt=2.589min(3分間のクロマトグラフィー)、10−80AB、C28H39FN3O2[M+H]+のMS ESI計算値468、実測値468.
1H NMR (23): (400 MHz, CDCl3) δ 7.70 (d,J=8Hz,1H), 7.28 (t, J=12Hz, 2H) ,5.46-5.35 (m, 2H), 2.71 (d, J=8Hz, 1H), 2.16-1.75 (m, 7H), 1.58-1.43 (m, 8H), 1.27-1.08 (m, 9H), 0.96 (s, 3H), 0.70 (s, 3H). LCMS Rt=2.569min(3分間のクロマトグラフィー)、10−80AB、C28H39FN3O2[M+H]+のMS ESI計算値468、実測値468.
1H NMR (24): (400 MHz, CDCl3) δ 7.48 (d,J=1.6Hz,1H), 6.72 (d, J=2.4Hz, 1H) , 5.04-4.89 (m, 2H), 2.60(d, J=4Hz, 1H), 2.58-1.72 (m, 8H), 1.58-1.42 (m, 8H), 1.31-1.07 (m, 10H),0.95 (s, 3H),0.65 (s, 3H). LCMS Rt=2.385min(3分間のクロマトグラフィー)、10−80AB、C26H38N3O2[M+H]+のMS ESI計算値424、実測値406[M+H−18]+.
1H NMR (25): (400 MHz, CDCl3) δ 7.50 (s,1H), 6.72 (d, J=2.4Hz, 1H) , 6.75 (s, 1H), 5.09-4.89 (m, 2H), 2.76 (d,J=4Hz,1H),1.88-1.81 (m, 8H), 1.57-1.41 (m, 8H), 1.38-1.20 (m, 10H),1.01 (d, J=48Hz, 6H). LCMS Rt=2.415min(3分間のクロマトグラフィー)、10−80AB、C26H37N3O2[M+H]+のMS ESI計算値424、実測値446[M+23]+.
1H NMR (26): (400 MHz, CDCl3) δ 7.93 (s ,1H), 7.68 (t, J=20Hz, 2H) , 7.29 (d, J=8Hz, 1H), 7.08 (t, J=16Hz, 2H) ,5.25-5.14 (m, 2H), 2.63 (d, J=8Hz, 1H), 2.20-1.72 (m, 9H), 1.57-1.42 (m, 6H), 1.26-1.07 (m, 10H), 0.95 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.194min(2分間のクロマトグラフィー)、30−90AB、C29H41N2O2[M+H]+のMS ESI計算値449、実測値449.
1HNMR (27): (400 MHz, CDCl3) δ 8.05 (s ,1H), 7.75 (t, J=8Hz, 1H) , 7.37 (d, J=8Hz, 1H), 7.22-7.14 (m, 2H) , 5.14 (m, 2H), 2.61 (t, J=16Hz, 1H), 2.22-1.69 (m, 9H), 1.55-1.42 (m,7H), 1.26-1.06 (m, 10H), 0.95 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.213min(2分間のクロマトグラフィー)、30−90AB、C29H41N2O2[M+H]+のMS ESI計算値449、実測値449.
1HNMR (28): (400 MHz, CDCl3) δ 7.30 (d , J=8Hz ,1H), 6.91 (t, J=20Hz, 1H), 5.55-5.46 (m, 2H), 2.65 (t, J=16Hz, 1H), 2.20 -1.74 (m, 8H), 1.60-1.43 (m,8H), 1.27-1.08 (m, 10H), 0.96 (s, 3H), 0.72 (s, 3H). LCMS Rt=2.662min(3分間のクロマトグラフィー)、10−80AB、化学式:C28H37F2N3O2[M+H]+のMS ESI計算値468、実測値468.
1H NMR (29): (400 MHz, CDCl3) δ 7.54 (d , J=8Hz ,2H), 7.00 (t, J=8Hz, 1H), 5.52-5.37 (m, 2H), 2.73-2.63 (m, 1H), 2.12 -1.75 (m, 9H), 1.59-1.45 (m,6H), 1.36-1.10 (m, 10H), 0.98 (s, 3H), 0.71 (s, 3H). LCMS Rt=2.576min(3分間のクロマトグラフィー)、10−80AB、C28H37F2N3O2[M+H]+のMS ESI計算値468、実測値468.
1HNMR (30): (400 MHz, CDCl3) δ 6.89-6.79 (m ,2H), 5.43-5.31 (m, 2H) , 2.70 (t, J=16Hz, 1H), 2.22-1.74 (m, 8H), 1.57-1.44 (m,8H), 1.35-1.08 (m, 10H), 0.97 (s, 3H), 0.70 (s, 3H). LCMS Rt=2.551min(3分間のクロマトグラフィー)、10−80AB、C28H37F2N3O2[M+H]+のMS ESI計算値468、実測値468.
1H NMR (31): (400 MHz, CDCl3) δ 5.16-5.02(m, 2H), 2.66-2.64 (m, 1H), 2.46 (s, 3H), 2.16-1.76 (m, 1H), 1.73-1.55 (m, 7H), 1.51-1.43 (m, 8H), 1.33-1.08 (m, 10H), 0.96 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.070min(2分間のクロマトグラフィー)、30−90AB、C24H39N4O2[M+H]+のMS ESI計算値415、実測値415.
1H NMR (32): (400 MHz, CDCl3) δ 5.34 (s, 2H), 2.62-2.56 (m, 4H), 2.17-2.06 (m, 1H), 1.96-1.52 (m, 8H), 1.49-1.27 (m, 7H), 1.23-1.09 (m, 10H), 0.95 (s, 3H), 0.69 (s, 3H). LCMS Rt=2.447min(3分間のクロマトグラフィー)、10−80AB、C24H39N4O2[M+H]+のMS ESI計算値415、実測値415.
1H NMR (33): (400 MHz, DMSO-d6) δ 8.32 (s,1H), 7.86 (s,1H) ,7.64 (d, J=8Hz, 1H) , 7.23 (d, J=8Hz, 1H), 5.55-5.34(m, 2H), 4.28 (s,1H), 2.51 (s,1H), 1.86 -1.47 (m, 7H), 1.40-1.38 (m, 6H), 1.27-1.02 (m, 9H), 0.93 (s, 3H), 0.61 (s, 3H). LCMS Rt=1.444min(2分間のクロマトグラフィー)、10−80AB、C29H39ClN2O2[M+H]+のMS ESI計算値483、実測値483.
1H NMR (34): (400 MHz, CDCl3) δ 7.98 (s,1H), 7.86 (s,1H) , 7.71 (d, J=1.6Hz, 1H) , 7.13 (d, J=0.8Hz, 1H), 5.16-5.07 (m, 2H), 2.62 (d, J=8.8Hz ,1H), 221-1.95 (m, 2H), 1.77-1.52 (m, 6H), 1.49-1.27 (m, 8H),1.25-1.08 (m, 8H) ,0.97 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.476min(2分間のクロマトグラフィー)、10−80AB、C29H39ClN2O2[M+H]+のMS ESI計算値483、実測値483.
1H NMR (35): (400 MHz, CDCl3) δ 7.87 (d , J=1.6Hz ,1H), 7.82 (d , J=4.4Hz ,1H), 7.36-7.33 (m, 1H), 5.54-5.45 (m, 2H), 2.65 (d, J=4Hz ,1H), 2.23-2.00 (m,2H), 1.96-1.58 (m, 5H), 1.51-1.42 (m, 9H), 1.27-1.08 (m, 10H), 0.96 (s, 3H), 0.72 (s, 3H). LCMS Rt=1.311min(2分間のクロマトグラフィー)、30−90AB、C28H38ClN3O2[M+H]+のMS ESI計算値484、実測値[M+H−18]+466.
1H NMR (36): (400 MHz, CDCl3) δ 8.00 (d , J=4.6Hz ,1H), 7.34 (d , J=6.4Hz ,2H), 5.44-5.31 (m, 2H), 2.71 (t, J=8.8Hz ,1H), 2.21-2.14 (m,2H), 1.97-1.74 (m, 6H), 1.59-1.52 (m, 9H), 1.44-1.09 (m, 10H), 0.97 (s, 3H), 0.71 (s, 3H). LCMS Rt=1.230min(2分間のクロマトグラフィー)、30−90AB、C28H38ClN3O2[M+H]+のMS ESI計算値484、実測値484.
1H NMR (37): (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.44 (d , J=8Hz ,1H), 7.30 (d, J=20Hz ,1H) 5.45-5.34 (m, 2H), 2.70 (d, J=4Hz ,1H), 2.19-2.17 (m,2H), 1.96-1.74 (m, 6H), 1.56-1.51 (m, 9H), 1.46-1.09 (m, 10H), 0.96 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.261min(2分間のクロマトグラフィー)、30−90AB、C28H38ClN3O2[M+H]+のMS ESI計算値484、実測値484.
1HNMR (38): (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.68-7.65 (m, 1H), 7.25 (t, J=2.4Hz, 1H), 7.09 (t, J=2.4Hz, 1H), 5.24-5.12 (m, 2H), 2.64 (t, J=8.4, 1H), 2.20-1.54 (m, 8H), 1.48-1.43 (m, 8H), 1.27-1.08 (m, 10H), 0.95 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.145min(2分間のクロマトグラフィー)、30−90AB、C30H41FN2O2[M+H]+のMS ESI計算値467、実測値467.
1HNMR (39): (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.35 (d, J=9.2Hz, 1H), 7.14 (d, J=6Hz, 1H), 5.12 (m, 2H), 2.61 (t, J=8.8, 1H), 2.20-1.95 (m, 2H), 1.72-1.53 (m, 7H), 1.43-1.10 (m, 18H), 0.95 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.117min(2分間のクロマトグラフィー)、30−90AB、C29H39FN2O2[M+H]+のMS ESI計算値467、実測値467.
1H NMR (A28): (400 MHz, CDCl3) δ 3.62-3.52 (m, 1H), 2.57-2.51 (m, 1H), 2.20-2.12(m, 4H), 2.05-1.98 (m, 1H), 1.87-1.78 (m, 1H), 1.75-1.58 (m, 6H), 1.45-1.09 (m, 11H), 1.03-0.89 (m, 2H), 0.81 (s, 3H), 0.71-0.63 (m, 1H), 0.60 (s, 3H).
1H NMR (A31): (400 MHz, CDCl3) δ 3.19-3.11 (m, 2H), 2.58-2.50 (m, 1H), 2.11 (s, 3H), 2.08-1.82 (m, 3H), 1.70-1.08 (m, 17H), 0.90-0.82 (m, 1H), 0.78 (s, 3H), 0.72-0.63 (m, 1H) , 0.59 (s, 3H).
1H NMR: (400 MHz, CDCl3) δ 3.95-3.88 (m, 3H), 3.60-3.52 (m, 1H), 3.45-3.37 (m, 2H), 2.83-2.78 (m, 1H), 2.23-2.13 (m , 1H), 1.94-1.78 (m, 3H), 1.80-1.61 (m, 4H), 1.44-1.12 (m, 14H), 0.96 -0.89 (m, 4H), 0.80-0.70 (m, 1H), 0.62 (s, 3H)
1H NMR (40): (400 MHz, CDCl3) δ 7.44 (d, J = 2 Hz, 1H), 6.87 (d, J = 2.4 Hz, 1H), 5.30 (s, 3H), 4.40 (dd, J =7.6 Hz, J =14.8 Hz, 2H), 3.96-3.91 (m, 1H), 3.60-3.53 (m, 1H), 3.47-3.38 (m , 2H), 2.60-2.52 (m, 1H), 2.21-2.11 (m, 1H), 2.07-2.00 (m, 1H), 1.90 -1.61 (m, 6H), 1.52-1.15 (m, 17H), 1.03 -0.92 (m, 4H), 0.82-0.72 (m, 1H), 0.66 (s, 3H)
1H NMR (A34): (400 MHz, CDCl3) δ 7.68 (s, 2H), 5.30-5.18 (m, 2H), 3.66-3.60 (m, 1H), 3.30 (s, 3H), 2.64-2.52 (m, 2H), 2.23-2.03 (m, 4H), 1.76-1.68 (m, 4H), 1.48-1.15 (m, 9H), 1.04 (s, 3H), 0.97-0.88 (m, 1H), 0.82-0.75 (m, 1H), 0.71 (s, 3H).
1H NMR (42): (400 MHz, CDCl3) δ 7.68 (s, 2H), 5.31-5.16 (m, 2H), 3.31 (s, 3H), 3.06-2.98 (m, 1H), 2.59-2.55 (m, 1H), 2.22-1.95 (m, 3H), 1.45-1.11 (m, 16H), 1.04-0.94 (m, 1H), 0.92 (s, 3H), 0.83 - 0.874 (m, 1H), 0.70 (s, 3H)
1H NMR (43): (400 MHz, CDCl3) δ 3.74 (t, J = 4.8 Hz, 1H), 3.21-3.11 (m, 2H), 2.62-2.45 (m, 5H), 2.22-2.10 (m, 1H), 2.00-1.05 (m, 25H), 0.93 (s, 3H), 0.60 (s, 3H). LCMS Rt=0.973min(2分間のクロマトグラフィー)、10−80AB、C26H44NO3[M+H]+のMS ESI計算値418、実測値418.
1HNMR (44): (400 MHz, CDCl3) δ 7.63 (d, J=8Hz, 1H), 7.23 (d, J=8.4Hz, 1H), 6.76 (d, J=8Hz, 1H), 5.58 (d, J=1.6Hz, 2H), 3.89 (s, 3H), 2.66 (t, J=8.4, 1H), 2.19-1.97 (m, 2H), 1.78-1.57 (m, 5H), 1.46-1.41 (m, 7H), 1.27-1.09 (m, 7H), 0.97 (s, 3H), 071 (s, 3H). LCMS Rt=0.943min(1.5分間のクロマトグラフィー)、5−95AB、C29H41N3O3[M+H]+のMS ESI計算値480、実測値480
1HNMR (45): (400 MHz, CDCl3) δ 7.38 (t, J=8Hz, 1H), 6.86 (d, J=8Hz, 1H), 6.69 (d, J=8.4Hz, 1H), 5.37 (s, 2H), 4.12 (s, 3H), 2.67 (t, J=8.4, 1H), 2.19-1.95 (m, 2H), 1.77-1.55 (m, 5H), 1.50-1.42 (m, 8H), 1.27-1.08 (m, 11H), 0.96 (s, 3H), 070 (s, 3H). LCMS Rt=1.113min(2分間のクロマトグラフィー)、30−90AB、C29H41N3O3[M+H]+のMS ESI計算値480、実測値480
1HNMR (46): (400 MHz, CDCl3) δ 7.43 (d, J=9.2Hz, 1H), 9.30 (t, J=8Hz, 1H), 6.64 (d, J=6.8Hz, 1H), 5.49 (s, 2H), 4.03 (s, 3H), 2.65-2.60 (m, 1H), 2.04-1.95 (m, 2H), 1.77-1.54 (m, 7H), 1.54-1.42 (m, 6H), 1.27-1.08 (m, 11H), 0.96 (s, 3H), 072 (s, 3H). LCMS Rt=1.168min(2分間のクロマトグラフィー)、30−90AB、C29H41N3O3[M+H]+のMS ESI計算値480、実測値[M+H−18]+462.
1HNMR (47) (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.68 (s, 1H), 7.20 (d, J=8.4Hz, 1H), 7.03 (t, J=8.4Hz, 1H), 5.23-5.11 (m, 2H), 2.63 (t, J=8.4, 1H), 2.22-1.95 (m,2H), 1.77 -1.54 (m, 5H), 1.45-1.07 (m, 19H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.214min(2分間のクロマトグラフィー)、30−90AB、C29H39ClN2O2[M+H]+のMS ESI計算値483、実測値483.
1HNMR (48): (400 MHz, CDCl3) δ 8.00 (s, 1H), 7.65 (d, J=8.4Hz, 1H), 7.20 (s, 1H), 7.14-7.11 (m, 1H), 5.14-5.04 (m, 2H), 2.64 (t, J=8.4, 1H), 2.17-1.96 (m,2H), 1.73 -1.52 (m, 6H), 1.48-1.11 (m, 18H), 0.96 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.239min(2分間のクロマトグラフィー)、30−90AB;C29H39ClN2O2[M+H]+のMS ESI計算値483、実測値483.
1HNMR (49): (400 MHz, CDCl3) δ 8.68 (d, J=2, 1H), 7.76 (d, J=2, 1H), 5.51-5.34 (m, 2H), 2.73 (t, J=8.8, 1H), 2.21-1.97 (m,2H), 1.78 -1.54 (m, 5H), 1.47-1.30 (m, 9H), 1.28-1.09 (m, 10H), 0.97 (s, 3H), 0.72 (s, 3H). LCMS Rt=1.137min(2分間のクロマトグラフィー)、30−90AB、C27H37ClN4O2[M+H]+のMS ESI計算値485、実測値467[M+H−18]+
1HNMR (50): (400 MHz, CDCl3) δ 8.73 (d, J=2, 1H), 8.22 (d, J=2, 1H), 5.59-5.49 (m, 2H), 2.66 (t, J=8.4, 1H), 2.17-1.96 (m,2H), 1.73 -1.53 (m, 6H), 1.45-1.43 (m, 8H), 1.27-1.08 (m, 10H), 0.96 (s, 3H), 0.72 (s, 3H). LCMS Rt=0.977min(1.5分間のクロマトグラフィー)、C27H37ClN4O2[M+H]+のMS ESI計算値485、実測値467[M+H−18]+
1HNMR (51): (400 MHz, CDCl3) δ 7.49-7.45 (m, 1H) , 7.06 (d, J=8.2, 1H), 5.47-5.35 (m, 2H), 2.71 (d, J=8.8, 1H), 2.19-1.96 (m,2H), 1.87 -1.55 (m, 7H), 1.46-1.44 (m, 6H), 1.27-1.09 (m, 11H), 0.96 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.234min(2分間のクロマトグラフィー)、30−90AB、C28H37ClFN3O2[M+H]+のMS ESI計算値502、実測値502.
1HNMR (52) (400 MHz, CDCl3) δ 7.79 (d, J=8.8, 1H) , 7.36-7.33 (m, 1H), 5.52 (s, 2H), 2.72 (d, J=8.4, 1H), 2.20-1.97 (m,2H), 1.84 -1.55 (m, 7H), 1.47-1.44 (m, 6H), 1.27-1.09 (m, 11H), 0.97 (s, 3H), 0.71 (s, 3H). LCMS Rt=1.013min(1.5分間のクロマトグラフィー)、C28H37ClFN3O2[M+H]+のMS ESI計算値502、実測値502.
1HNMR (53): (400 MHz, CDCl3) δ 7.63 (t, J=8.8, 1H), 7.38-7.34 (m, 1H), 5.57-5.48 (m, 2H), 2.65 (t, J=8.8, 1H), 2.20-2.04 (m,2H), 1.77 -1.57 (m, 6H), 1.45-1.43 (m, 7H), 1.27-1.08 (m, 11H), 0.96 (s, 3H), 0.72 (s, 3H). LCMS Rt=1.310min(2分間のクロマトグラフィー)、C28H37ClFN3O2[M+H]+のMS ESI計算値502、実測値484[M+H−18]+.
1HNMR (54): (400 MHz, CDCl3) δ 8.57 (s, 1H), 5.45 (s ,2H), 2.63 (t, J=8.8Hz ,1H), 2.19-1.54 (m, 8H), 1.50-1.43 (m, 7H), 1.27-1.08 (m, 11H), 0.96 (s, 3H), 0.70 (s, 3H). LCMS Rt=0.899min(1.5分間のクロマトグラフィー)、C23H36N4O2[M+H]+のMS ESI計算値401、実測値[M+H−18]+383
1HNMR (55): (400 MHz, CDCl3) δ 8.74 (s, 1H), 5.33-5.16 (m ,2H), 2.67 (d, J=8.8Hz ,1H), 2.20-1.54 (m, 8H), 1.51-1.43 (m, 8H), 1.31-1.09 (m, 10H), 0.95(s, 3H), 0.65 (s, 3H). LCMS Rt=0.8827min(1.5分間のクロマトグラフィー)、C23H36N4O2[M+H]+のMS ESI計算値401、実測値[M+H−18]+383
1H NMR (A35): (400 MHz, CDCl3) δ 7.69 (s, 2H), 5.28-5.19 (m, 2H), 2.59-2.55 (m, 1H), 0.95 (s, 3H), 0.69 (s, 3H).
1H NMR (A36): (400 MHz, CDCl3) δ 7.76 (d, J = 8Hz, 1H), 7.64 (d, J = 8Hz, 1H), 5.29-5.11 (m, 2H), 2.66-2.62 (m, 1H), 0.95 (s, 3H), 0.66 (s, 3H).
1H NMR (56): (400 MHz, CDCl3) δ 7.68 (s, 2H), 5.25 (q, J = 6.8 Hz, 1H), 2.23-2.14 (m, 1H), 2.10-2.00 (m, 1H), 1.90-1.75 (m, 3H), 1.58-1.50 (m, 5H), 1.49-1.25 (m, 8H), 1.24-1.07 (m, 9H),1.04-1.00 (m, 3H), 0.95 (s, 3H), 0.64 (s, 3H). LCMS Rt=0.945min(1.5分間のクロマトグラフィー)、C25H39N3O2[M+H]+のMS ESI計算値414、実測値396([M+H−18]
1H NMR (57): (400 MHz, CDCl3) δ 7.67 (s, 2H), 5.40 (q, J = 7.6 Hz, 1H), 2.65-2.63 (m, 1H), 2.14-2.12 (m, 2H), 1.95-1.66 (m, 5H), 1.60-1.49 (m, 3H), 1.55-1.25 (m, 10H), 1.42-1.00 (m, 10H), 0.95 (s, 3H), 0.67 (s, 3H). LCMS Rt=0.927min(1.5分間のクロマトグラフィー)、C25H39N3O2[M+H]+のMS ESI計算値414、実測値396([M+H−18]+
1H NMR (58): (400 MHz, CDCl3) δ 7.77 (s, 1H), 7.60 (s, 1H), 5.47 (q, J = 7.6Hz, 1H), 2.56-2.51 (m, 1H), 2.15-2.00 (m, 1H), 1.90-1.75 (m,3H), 1.66-1.64 (m, 3H), 1.60-1.54 (m, 2H), 1.50-1.39 (m, 9H), 1.25-1.00 (m, 11H), 0.94 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.054min(2分間のクロマトグラフィー)、C25H39N3O2[M+H]+のMS ESI計算値414、実測値396([M+H−18]
1H NMR (59): (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.74 (s, 1H), 5.64 (q, J = 7.2Hz, 1H), 2.80-2.78 (m, 1H), 2.22-2.20 (m, 2H), 1.96-1.75 (m,2H), 1.69-1.54 (m, 6H), 1.58-1.43 (m, 9H), 1.40-1.00 (m, 10H), 0.93 (s, 3H), 0.51 (s, 3H). LCMS Rt=1.012min(2分間のクロマトグラフィー)、C25H39N3O2[M+H]+のMS ESI計算値414、実測値396([M+H−18]
1H NMR (A37): 400MHz δ 7.87 (dd, J1 = 3.2Hz, J2 = 6.4Hz, 2H), 7.39 (dd, J1 = 3.2Hz, J2 = 6.8Hz, 2H), 5.52-5.51 (m, 2H), 2.65-2.63 (m, 1H), 0.96 (s, 3H), 0.73 (s, 3H).
1H NMR (A38): 400MHz δ 8.09 (d, J = 8.4Hz, 1H), 7.49-7.47 (m, 1H), 7.40-7.26 (m, 2H), 5.42-5.41 (m, 2H),2.72-2.68 (m, 1H), 0.96 (s, 3H), 0.71 (s, 3H).
1H NMR (60): 400MHzδ 7.88 (dd, J1 = 3.2Hz, J2 = 6.8Hz, 2H), 7.40 (dd, J1 = 3.2Hz, J2 = 6.8Hz, 2H), 5.74-5.68 (m, 1H), 2.74-2.69 (m, 1H), 2.25-2.1(m, 1H), 2.00-1.75(m, 8H), 1.60-1.29 (m, 10H), 1.28-1.25 (m, 8H), 1.25-1.00 (m, 2H), 0.97 (s, 3H), 0.73 (s, 3H). LCMS Rt=0.997min(1.5分間のクロマトグラフィー)、C29H41N3O2[M+H]+のMS ESi計算値464、実測値446([M+H−18]
1H NMR (61): 400MHz δ 7.88 (dd, J1 = 2.8Hz, J2 = 6.4Hz, 2H), 7.42 (dd, J1 = 3.2Hz, J2 = 6.4Hz, 2H), 5.54-5.49 (m,1H), 2.26-2.05 (m, 2H), 1.95-1.50 (m, 8H), 1.48-1.30 (m, 8H), 1.28-1.15 (m, 9H), 1.13-1.04 (m, 3H), 0.93 (s, 3H), 0.67 (s, 3H)
LCMS Rt=1.006min(1.5分間のクロマトグラフィー)、C29H41N3O2[M+H]+のMS ESi計算値464、実測値446([M+H−18]
1H NMR (62): 400MHz δ 8.09 (d, J = 8.0Hz, 1H), 7.57-7.55 (m, 1H), 7.49-7.47 (m, 1H), 7.39-7.37 (m, 1H), 5.81-5.79 (m, 1H), 2.72-2.68 (m, 1H), 2.01-1.75 (m, 8H), 1.65-1.55 (m, 2H), 1.50-1.25(m, 8H), 1.24-1.00 (m, 11H), 0.93 (s, 3H), 0.61 (s, 3H). LCMS tR=1.161min(2分間のクロマトグラフィー)、30−90AB、C29H41N3O2[M+H]+のMS ESI計算値464、実測値446([M+H−18]
1H NMR (63): 400MHz δ 8.10 (d, J = 7.6Hz, 1H), 7.51-7.47 (m, 1H), 7.42-7.39 (m, 2H), 5.64-5.58 (m, 1H), 2.36-2.33 (m, 1H), 2.20-2.00 (m, 1H), 1.77-1.57 (m, 7H), 1.50-1.25(m, 10H), 1.25-1.10 (m, 8H), 1.24-1.03 (m, 3H), 0.92 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.186min(2分間のクロマトグラフィー)、C29H41N3O2[M+H]+のMS ESI計算値464、実測値446([M+H−18]
1HNMR (64): (400 MHz, CDCl3) δ 8.64 (s, 1H), 8.56 (s, 1H), 8.27 (s, 1H), 5.37-5.21 (m, 2H), 2.70 (t, J=8.4, 1H), 2.22-1.96 (m, 2H), 1.77 -1.58 (m, 6H), 1.51-1.43 (m, 8H), 1.27-1.08 (m, 10H), 0.96 (s, 3H), 0.69 (s, 3H). LCMS Rt=0.937min(2分間のクロマトグラフィー)、C27H38N4O2[M+H]+のMS ESI計算値451、実測値473[M+23]+.
1HNMR (65): (400 MHz, CDCl3) δ 8.58 (d, J=1.6Hz, 1H), 8.44 (d, J=2Hz, 1H), 8.34 (s, 1H), 5.36-5.25 (m, 2H), 2.70 (t, J=8.4, 1H), 2.24-1.87 (m, 2H), 1.74 -1.54 (m, 6H), 1.46-1.43 (m, 8H), 1.27-1.08 (m, 10H), 0.96 (s, 3H), 0.70 (s, 3H). LCMS Rt=0.916min(1.5分間のクロマトグラフィー)、C27H38N4O2[M+H]+の451、実測値451.
1HNMR (66): (400 MHz, CDCl3) 7.94 (s,1H) ,7.66-7.62 (m, 1H) , 7.29 (s, 1H), 6.90 (t, J=8Hz, 1H), 5.18 (s, 2H), 2.64 (s,1H), 2.13-2.00 (m,2H), 1.95 -1.54 (m, 6H), 1.49-1.43 (m, 8H), 1.27-1.08 (m, 10H), 0.95 (s, 3H), 0.69 (s, 3H). LCMS Rt=0.949min(1.5分間のクロマトグラフィー)、C30H41FN2O2[M+H]+のMS ESI計算値467、実測値467.
1HNMR (67): (400 MHz, CDCl3) δ 8.01 (s,1H) ,7.69-7.66 (m, 1H) , 6.96-6.93 (m, 1H), 6.91-6.83 (m, 1H), 5.12-5.03 (m, 2H), 2.62 (t, J=9.2, 1H), 2.17-1.95 (m,2H), 1.77 -1.54 (m, 6H), 1.47-1.43 (m, 8H), 1.27-1.07 (m, 10H), 0.73 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.151min(2分間のクロマトグラフィー)、C29H39FN2O2[M+H]+のMS ESI計算値467、実測値467.
1HNMR (68): (400 MHz, CDCl3) δ 7.82 (t, J=8.4, 1H), 7.12 (t, J=8, 1H), 5.44-5.31 (m, 2H), 2.72 (t, J=8.4, 1H), 2.19-1.96 (m, 2H), 1.87 -1.70 (m, 7H), 1.43-1.27 (m, 5H), 1.12-1.08 (m, 11H), 0.96 (s, 3H), 0.69 (s, 3H). LCMS Rt=0.968min(1.5分間のクロマトグラフィー)、C28H37F2N3O2[M+H]+のMS ESI計算値486、実測値486.
1HNMR (69): (400 MHz, CDCl3) δ 7.60 (t, J=8Hz, 2H), 5.52-5.42 (m, 2H), 2.64 (t, J=9.2, 1H), 2.14-1.96 (m, 2H), 1.87 -1.53 (m, 6H), 1.47-1.43 (m, 9H), 1.27-1.08 (m, 10H), 0.97 (s, 3H), 0.72 (s, 3H). LCMS Rt=1.004min(1.5分間のクロマトグラフィー)、C28H37F2N3O2[M+H]+のMS ESI計算値486、実測値[M+H−18]+468.
1HNMR (71): (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.87 (s , 1H), 5.04-4.89 (m, 2H), 3.13 (s, 3H), 2.62 (d, J=9.2Hz ,1H) , 2.19-1.52 (m,7H), 1.47-1.43 (m, 9H), 1.27-1.09 (m, 11H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.265min(2分間のクロマトグラフィー)、化学式:C26H40N2O4S[M+H]+のMS ESI計算値477、実測値[M+H−18]+459.
1H NMR (A39): 400MHz δ 7.86 (s, 1H), 7.81 (s, 1H), 5.04-4.88 (m, 2H), 2.62-2.58 (m, 1H), 0.95 (s, 3H), 0.65 (s, 3H).
1H NMR (72): 400MHz δ 7.99 (s, 1H), 7.77 (s, 1H), 5.26 (q, J = 7.6 Hz, 1H), 2.71-2.62 (m, 1H), 2.18-2.16 (m, 2H), 2.00-1.72 (m, 2H), 1.70-1.65 (m, 6H), 1.52-1.41 (m, 10H), 1.43-1.02 (m, 11H), 0.94 (s, 3H), 0.55 (s, 3H). LCMS Rt=1.122min(2分間のクロマトグラフィー)、C27H39N3O2[M+H−18]+のMS ESI計算値420、実測値460([M+23]
1H NMR (73): 400MHz δ 7.77 (s, 1H), 7.72 (s, 1H), 5.04 (q, J = 7.6 Hz, 1H), 2.49-2.47 (m, 1H), 2.07-2.00 (m, 1H), 1.92-1.88 (m,3H), 1.67-1.62(m, 6H), 1.60-1.40 (m, 8H), 1.27-1.06 (m, 11H), 0.94 (s, 3H), 0.65 (s, 3H). LCMS Rt=1.132min(2分間のクロマトグラフィー)、C27H39N3O2[M+H−18]+のMS ESI計算値420、実測値460([M+Na]+.
1HNMR (74) (400 MHz, CDCl3) δ 7.75 (d, J=8.8Hz, 1H), 7.57 (s, 1H), 7.28 (d, J=1.6Hz, 1H) 5.51-5.41 (m, 2H), 2.63 (t, J=8.4, 1H), 2.55 (s, 3H), 2.20-1.95 (m, 2H), 1.77-1.59 (m, 5H), 1.54-1.42 (m, 9H), 1.27-1.08 (m, 11H), 0.96 (s, 3H), 0.72 (s, 3H).LCMS Rt=1.468min(2分間のクロマトグラフィー)、C29H41N3O2S[M+H]+のMS ESI計算値496、実測値478[M+H−18]+.
1HNMR (75) (400 MHz, CDCl3) δ 7.87 (s, 1H), 7.40 (d, J=9.2Hz, 1H), 7.23 (d, J=8.8Hz, 1H) 5.42-5.32 (m, 2H), 2.70-2.66 (m, 1H), 2.56 (s, 3H), 1.96-1.52 (m, 7H), 1.45-1.43 (m, 8H), 1.27-1.08 (m, 11H), 0.96 (s, 3H), 0.69 (s, 3H). LCMS Rt=0.963min(1.5分間のクロマトグラフィー)、C29H41N3O2S[M+H]+のMS ESI計算値496、実測値496.
1HNMR (76): (400 MHz, CDCl3) δ 7.93 (d, J=8.8Hz, 1H), 7.27-7.25 (m, 1H), 5.40-5.30 (m, 2H), 2.69 (t, J=8.8, 1H), 2.53 (s, 3H), 2.22-1.96 (m, 2H), 1.77-1.52 (m, 8H), 1.51-1.27 (m, 6H), 1.24-1.08 (m, 12H), 0.96 (s, 3H), 0.71 (s, 3H). LCMS Rt=1.160min(2分間のクロマトグラフィー)、C29H41N3O2S[M+H]+のMS ESI計算値496、実測値496.
1HNMR (77): (400 MHz, CDCl3) δ 7.40-7.35 (m, 1H), 7.06-7.04 (m, 1H), 5.46-5.35 (m, 2H), 2.71 (d, J=8.4Hz ,1H), 2.18-1.96 (m,2H), 1.76-1.54 (m, 5H), 1.45-1.30 (m, 7H), 1.27-1.08 (m, 10H), 0.96 (s, 3H), 0.67 (s, 3H). LCMS Rt=0.973min(1.5分間のクロマトグラフィー)、C28H37F2N3O2[M+H]+のMS ESI計算値468、実測値468.
1HNMR (78): (400 MHz, CDCl3) δ 7.38-7.33 (m, 1H), 7.06-7.04 (m, 1H), 5.46-5.35 (m, 2H), 2.71 (d, J=8.8Hz ,1H), 2.15-1.96 (m,2H), 1.77-1.54 (m, 6H), 1.46-1.43 (m, 6H), 1.27-1.09 (m, 10H), 0.96 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.252min(2分間のクロマトグラフィー)、C28H37F2N3O2[M+H]+のMS ESI計算値468、実測値468.
1H NMR (A41): 400MHz δ 2.53-2.48 (m, 1H), 2.00 (S, 3H),1.81-1.58 (m, 9H), 1.38-1.16 (m,12H), 1.29-1.07 (m, 10H), 0.98 (s, 3H), 067 (s, 3H).
工程2。A42の合成。A41(21g、65.9mmol)のDCM(300mL)中の溶液に、Dess−Martin試薬(41.9g、98.8mmol)を0℃で添加した。添加後、この混合物を25℃で3時間撹拌した。このとき、H NMRが、出発物質が消費され、所望の生成物が生成されたことを示した。この反応をNa2S2O3(3g)、飽和NaHCO3(50mL)溶液でクエンチし、Na2SO4(10g)で乾燥させ、そして濃縮して、A42(20g)を白色固体として得、これをさらに精製せずに次の工程で直接使用した。
1HNMR (A42): 400MHz δ 2.55-2.53 (m, 1H), 2.27-2.03 (m, 4H), 2.00 (S, 3H),1.69-1.62(m, 3H), 1.43-1.19 (m, 14H), 0.92(s, 3H), 062(s, 3H).
1H NMR (A43): (400 MHz, CDCl3) δ 2.52 (t, J = 8.8 Hz, 1H), 2.17-2.12 (m, 1H), 2.11 (s, 3H), 1.70-1.18 (m, 23H), 1.05-0.85 (m, 1H), 0.80-0.79 (m, 1H), 0.74 (s, 3H), 0.59 (s, 3H).
1H NMR (A44): (400 MHz, CDCl3) δ 3.94-3.87 (m, 2H), 2.81 (t, J = 8.8Hz, 1H), 2.18-2.11 (m, 1H), 1.95-1.85 (m, 1H), 1.80-1.10 (m, 22H), 1.00-0.75 (m, 2H), 0.74 (s, 3H), 0.62 (s, 3H).
1H NMR (79): (400 MHz, CDCl3) δ 7.85 (s, 1H), 7.80 (s, 1H), 5.03-4.86 (m, 2H), 2.59 (t, J = 8.4Hz,1H), 2.25-2.10 (m, 1H), 2.05-1.95 (m, 1H), 1.80-1.15 (m, H), 1.05-0.76 (m, 4H), 0.75 (s, 3H), 0.65 (s, 3H). LCMS Rt=1.312min(2分間のクロマトグラフィー)、C26H38N3O2[M+H]+のMS ESI計算値423、実測値406[M+H−H2O]+.
1H NMR (80): (400 MHz, CDCl3) δ 7.86 (s, 1H), 7.80 (s, 1H), 5.07-5.01 (m, 1H), 2.49 (t, J = 8.8Hz, 1H), 2.15-1.80 (m, 2H), 1.75-1.15 (m, 25H), 0.95-0.85 (m, 1H), 0.84-0.75 (m, 1H), 0.74 (s, 3H), 0.65 (s, 3H). LCMS Rt=1.370min(2分間のクロマトグラフィー)、C27H40N3O2[M+H]+のMS ESI計算値438、実測値420[M+H−H2O]+.
1H NMR (81): (400 MHz, CDCl3) δ 7.99 (s, 1H), 7.77 (s, 1H), 5.30-5.24 (m, 1H), 2.73 (t, J = 8.8Hz, 1H), 2.17-2.14 (m, 2H), 1.75-1.15 (m, 25H), 1.00-0.90 (m, 1H), 0.85-0.75 (m, 1H), 0.74 (s, 3H), 0.55 (s, 3H). LCMS Rt=1.374min(2分間のクロマトグラフィー)、C27H40N3O2[M+H]+のMS ESI計算値438、実測値420[M+H−H2O]+.
1HNMR (106): (400MHz, Methanol-d4) δ 8.00 (s, 1H), 783 (s, 1H), 5.16-5.07 (m, 2H), 3.29 (s, 3H), 3.10 (s, 3H), 2.75 (t, J = 8.8 Hz, 1H), 2.20-2.17 (m, 2H), 1.77-1.25 (m, 25H), 1.18-0.85 (m, 3H), 0.82 (s, 3H), 0.70 (s, 3H). LCMS:Rt=0.861min(1.5分間のクロマトグラフィー)、C28H43N3O3[M+Na]+のMS ESI計算値492、実測値492.
1H NMR (A45): (400 MHz, CDCl3) δ 7.73 (s, 1H), 7.63 (s, 1H), 5.28-5.10 (m, 2H), 2.63 (t, J = 8.8Hz,1H), 2.25-2.10 (m, 1H), 1.80-0.80 (m, 25H), 0.68 (s, 3H), 0.65 (s, 3H).
1H NMR (A46): (400 MHz, CDCl3) δ 7.73 (s, 2H), 5.29-5.18 (m, 2H), 2.57 (t, J = 8.4Hz,1H), 2.25-2.10 (m, 1H), 1.80-0.80 (m, 25H), 0.75 (s, 3H), 0.69 (s, 3H).
1H NMR (90): (400 MHz, CDCl3) δ 7.66 (s, 2H), 5.28-5.22 (m, 1H), 2.24 (t, J = 8.8Hz, 1H), 2.14-1.95 (m, 3H), 1.85-1.70 (m, 3H), 1.65-0.75 (m, H), 0.71(s, 3H), 0.64 (s, 3H). LCMS Rt=1.381min(2分間のクロマトグラフィー)、C25H39N3O2[M+H]+のMS ESI計算値414、実測値414.
1H NMR (91): (400 MHz, CDCl3) δ7.66 (s, 2H), 5.43-5.37 (m, 1H), 2.65 (t, J = 8.8Hz, 1H), 2.14-1.95 (m, 3H), 1.85-1.70 (m, 3H), 1.65-0.75 (m, 23H), 0.74 (s, 3H), 0.67 (s, 3H). LCMS Rt=1.349min(2分間のクロマトグラフィー)、C25H39N3O2[M+H]+のMS ESI計算値414、実測値414.
1H NMR (92): (400 MHz, CDCl3) δ 7.76 (s, 1H), 7.60 (s, 1H), 5.48-5.46 (m, 1H), 2.57 (t, J = 8.8Hz, 1H), 2.15-1.05 (m, 26H), 1.00-0.74 (m, 3H), 0.74 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.295min(2分間のクロマトグラフィー)、C25H39N3O2[M+H]+のMS ESI計算値414、実測値414.
1H NMR (93): (400 MHz, CDCl3) δ 7.79 (s, 1H), 7.75 (s, 1H), 5.68-5.64 (m, 1H), 2.78 (t, J = 8.8Hz, 1H), 2.20-2.14 (m, 2H), 1.75-1.15 (m, 25H), 1.00-0.90 (m, 1H), 0.85-0.75 (m, 1H), 0.73 (s, 3H), 0.51 (s, 3H). LCMS Rt=1.260min(2分間のクロマトグラフィー)、C25H39N3O2[M+H]+のMS ESI計算値414、実測値414.
1H NMR (96): (400 MHz, CDCl3) δ 7.88-7.86 (m, 2H), 7.40-7.37 (m, 2H), 5.56-5.51 (m, 2H), 2.65 (t, J = 8.8Hz,1H), 2.25-2.10 (m, 2H), 1.80-0.80 (m, 24H), 0.75 (s, 3H), 0.73 (s, 3H).
1H NMR (97): (400 MHz, CDCl3) δ 8.09-8.07 (m, 1H), 7.50-7.40 (m, 1H), 7.39-7.32 (m, 2H), 5.46-5.36 (m, 2H), 2.70 (t, J = 8.8Hz,1H), 2.25-2.10 (m, 2H), 1.80-0.80 (m, 24H), 0.77 (s, 3H), 0.72 (s, 3H).
1H NMR (98): (400 MHz, CDCl3) δ7.89-7.86 (m, 2H), 7.42-7.38 (m, 2H), 5.54-5.49 (m, 1H), 2.26 (t, J = 8.Hz, 1H), 2.20-2.05 (m, 2H), 1.85-1.75 (m, 3H), 1.75-0.78 (m, 24H), 0.69 (s, 3H), 0.67 (s, 3H). LCMS Rt=1.493min(2分間のクロマトグラフィー)、C29H42N3O2[M+H]+のMS ESI計算値464、実測値446[M+H−H2O]+.
1H NMR (99): (400 MHz, CDCl3) δ7.89-7.86 (m, 2H), 7.39-7.36 (m, 2H), 5.72-5.66 (m, 1H), 2.71 (t, J = 8.Hz, 1H), 2.19-2.05 (m, 2H), 2.00-1.90 (m, 3H), 1.75-0.78 (m, 24H), 0.75 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.466min(2分間のクロマトグラフィー)、C29H42N3O2[M+H]+のMS ESI計算値464、実測値464.
1H NMR (100): (400 MHz, CDCl3) δ 8.09-8.07 (m, 1H), 7.48-7.36 (m, 3H), 5.64-5.59 (m, 1H), 2.34 (t, J = 8.8Hz, 1H), 2.15-1.75 (m, 2H), 1.74-1.70 (m, 3H), 1.70-0.75 (m, 24H), 0.71 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.411min(2分間のクロマトグラフィー)、C29H42N3O2[M+H]+のMS ESI計算値464、実測値464.
1H NMR (101): (400 MHz, CDCl3) δ 8.08-8.06 (m, 1H), 7.56-7.54 (m, 1H), 7.49-7.47 (m, 1H), 7.37-7.35 (m, 1H), 5.81-5.75 (m, 1H), 2.70 (t, J = 8.8Hz, 1H), 2.15-1.95 (m, 2H), 1.95-1.85 (m, 3H), 1.70-0.75 (m, 24H), 0.73 (s, 3H), 0.61 (s, 3H). LCMS Rt=1.391min(2分間のクロマトグラフィー)、C29H42N3O2[M+H]+のMS ESI計算値464、実測値464.
1H NMR (102): (400 MHz, CDCl3) δ 8.09-8.07 (m, 1H), 7.43-7.34 (m, 3H), 2.32 (t, J = 8.8Hz, 1H), 2.05 (s, 3H), 1.90 (s, 3H), 1.70-1.00 (m, 22H), 0.90-0.50 (m, 10H). LCMS Rt=1.467min(2分間のクロマトグラフィー)、C30H44N3O2[M+H]+のMS ESI計算値478、実測値478.
1H NMR: (103): 400MHz δ 8.29 (s, 1H), 8.03 (d, J=9.2Hz, 1H), 7.55 (t, J=7.2Hz, 1H), 5.61-5.51 (m, 2H), 2.78 (s, 3H), 2.68 (d, J=8.8Hz, 1H), 2.17-2.15 (m, 2H), 1.96-1.53 (m, 5H), 1.49-1.43 (m, 8H), 1.27-1.08 (m, 12H), 0.96 (s, 3H), 0.73 (s, 3H). LCMS Rt=0.877min(1.5分間のクロマトグラフィー)、C29H41N3O3S[M+H]+のMS ESI計算値512、実測値494[M+H−18]+.
1H NMR: (104): 400MHz δ 8.62 (s, 1H), 8.07 (d, J=9.2Hz, 1H), 7.88 (t, J=1.6Hz, 1H), 5.64-5.55 (m, 2H), 3.12 (s, 3H), 2.68 (t, J=8.8Hz, 1H), 2.21-2.17 (m, 2H), 1.96-1.54 (m, 6H), 1.51-1.44 (m, 9H), 1.27-1.09 (m, 11H), 0.97 (s, 3H), 0.73 (s, 3H). LCMS Rt=0.913min(1.5分間のクロマトグラフィー)、C29H41N3O4S[M+H]+のMS ESI計算値528、実測値510[M+H−18]+.
1HNMR (105): (400 MHz, CDCl3) δ 8.09 (d, J=8.8Hz, 1H), 7.27 (s, 1H), 7.18 (s, 1H), 5.47-5.35 (m, 2H), 2.72 (t, J=8.4, 1H), 2.21-1.97 (m, 2H), 1.86 -1.55 (m, 5H), 1.47-1.44 (m, 10H),1.29-1.09(m, 8H), 0.97 (s, 3H), 0.71 (s, 3H). LCMS Rt=0.994min(1.5分間のクロマトグラフィー)、C29H38F3N3O3[M+H]+のMS ESI計算値534、実測値534.
1H NMR (400 MHz, CDCl3) δ 2.44-2.22 (m, 4H), 2.15-1.75 (m, 6H), 1.70-1.20 (m, 10H), 1.10-0.65 (m, 8H).
1H NMR (400 MHz, CDCl3) δ 3.91-3.90 (m, 2H), 2.85-2.75 (m, 1H), 2.25-1.80 (m, 2H), 1.75-1.10 (m, 20H), 1.05-0.63 (m, 10H).
化合物107:1H NMR (400 MHz, CDCl3) δ 7.38-7.33 (m, 1H), 7.06-7.03 (m, 1H), 5.46-5.34 (m, 2H), 2.71 (t, J = 8.8Hz, 1H), 2.21-2.14 (m, 2H), 1.80-1.15 (m, 22H), 1.05-0.80 (m, 2H), 0.77 (s, 3H), 0.70 (s, 3H). LCMS:Rt=1.421min(2分間のクロマトグラフィー)、C28H38F2N3O2[M+H]+のMS ESI計算値486、実測値486.
化合物108:1H NMR (400 MHz, CDCl3) δ 7.65-7.62 (m, 1H), 7.31-7.25 (m, 1H), 5.57-5.47 (m, 2H), 2.66 (t, J = 8.8Hz, 1H), 2.30-2.14 (m, 2H), 1.80-1.15 (m, 22H), 1.05-0.73 (m, 8H). LCMS Rt=1.475min(2分間のクロマトグラフィー)、C28H38F2N3O2[M+H]+のMS ESI計算値486、実測値468[M+H−18]+.
化合物109:1H NMR (400 MHz, CDCl3) δ 7.44-7.40 (m, 1H), 7.12-7.09 (m, 1H), 7.09-7.03 (m, 1H), 5.47-5.36 (m, 2H), 2.70 (t, J = 8.8 Hz, 1H), 2.21-2.16 (m, 2H), 1.80-1.10 (m, 21H), 1.05-0.55 (m, 9H). LCMS:Rt=1.387min(2分間のクロマトグラフィー)、C28H39FN3O2[M+H]+のMS ESI計算値468、実測値468.
化合物110:1H NMR (400 MHz, CDCl3) δ 7.89 - 7.82 (m, 1H), 7.33 - 7.27 (m, 1H), 7.18 - 7.07 (m, 1H), 5.54 (s, 2H), 2.76 - 2.67 (m, 1H), 2.27 - 2.10 (m, 3H), 1.81-1.10 (m, 19H), 1.09 - 0.80 (m, 4H), 0.77 (s, 3H), 0.72 (s, 3H). LCMS:Rt=1.408min(2分間のクロマトグラフィー)、C28H39FN3O2[M+H]+のMS ESI計算値468、実測値468.
化合物111:1H NMR: (400 MHz, CDCl3) δ7.48-7.45 (m, 1H), 7.07-7.05 (m, 1H), 5.46-5.34 (m, 2H), 2.73-2.68 (m, 1H), 2.21-2.17 (m, 2H), 1.87-1.11 (m, 21H), 1.07-0.70 (m, 9H). LCMS:Rt=1.460min(2分間のクロマトグラフィー)、C28H38FClN3O2[M+H]+のMS ESI計算値502、実測値502.
化合物112:1H NMR: (400 MHz, CDCl3) δ7.62 (d, J=8.8 Hz, 1H), 7.37 (d, J=6.8 Hz, 1H), 5.52 (d, J=5.3 Hz, 2H), 2.75-2.58 (m, 1H), 2.33-2.06 (m, 2H), 1.87-1.11 (m, 21H), 1.06-0.64 (m, 9H). LCMS:Rt=1.525min(2分間のクロマトグラフィー)、C28H38FClN3O2[M+H]+のMS ESI計算値502、実測値484[M+H−18]+.
化合物113:1H NMR: (400 MHz, CDCl3) δ7.82-7.74 (m, 1H), 7.38-7.30 (m, 1H), 5.52 (s, 2H), 2.79-2.63 (m, 1H), 2.28-2.07 (m, 2H), 1.90-1.13 (m, 21H), 1.10-0.63 (m, 9H). LCMS:Rt=1.482min(2分間のクロマトグラフィー)、C28H38FClN3O2[M+H]+のMS ESI計算値502、実測値484[M+H−18]+.
化合物114:1H NMR (400 MHz, CDCl3) δ7.52(s, 1H), 7.41 (s, 1H), 4.93-4.79 (m, 2H), 2.57 (t, J = 8.8Hz, 1H), 2.34 (s, 3H), 2.17-1.95 (m, 2H), 1.80-1.10 (m, 21H), 1.05-0.65 (m, 9H). LCMS:Rt=1.369min(2分間のクロマトグラフィー)、C26H41SN2O2[M+H]+のMS ESI計算値445、実測値445.
化合物115:1H NMR (400 MHz, CDCl3) δ7.40-7.36 (m, 1H), 6.87-6.85 (m, 1H), 6.70-6.68 (m, 1H), 5.37-5.35 (m, 2H), 4.12 (s, 3H), 2.69-2.65 (m, 1H), 2.21-2.17 (m, 2H), 1.87-1.11 (m, 21H), 1.07-0.70 (m, 9H). LCMS:Rt=1.384min(2分間のクロマトグラフィー)、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
化合物116:1H NMR (400 MHz, CDCl3) δ7.66-7.59 (m, 1H), 7.25-7.20 (m, 1H), 6.79-6.73 (m, 1H), 5.64-5.52 (m, 2H), 3.89 (s, 3H), 2.7 -2.63 (m, 1H), 2.25-2.10 (m, 2H), 1.82-1.14 (m, 22H), 1.04-0.79 (m, 2H), 0.79-0.68 (m, 6H). LCMS:Rt=1.373min(2分間のクロマトグラフィー)、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
化合物117:1H NMR (400 MHz, CDCl3) δ7.44-7.42 (m, 1H), 7.31-7.27 (m, 1H), 6.64-6.63 (m, 1H), 5.54-5.45 (m, 2H), 4.02 (s, 3H), 2.65-2.60 (m, 1H), 2.21-2.10 (m, 2H), 1.87-1.11 (m, 21H), 1.07-0.70 (m, 9H). LCMS:Rt=1.397min(2分間のクロマトグラフィー)、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
化合物118:1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 5.49-5.30 (m, 2H), 2.64 (t, J = 8.8Hz, 1H), 2.22-2.06 (m, 2H), 1.80-1.10 (m, 19H), 1.05-0.70 (m, 9H). LCMS:Rt=1.305min(2分間のクロマトグラフィー)、C23H37N4O2[M+H]+のMS ESI計算値401、実測値401.
化合物119:1H NMR (400 MHz, CDCl3) δ 8.09-8.06 (m, 1H), 7.50-7.32(m, 3H), 5.46-5.36 (m, 2H), 2.70 (t, J = 8.8Hz, 1H), 2.24-2.16 (m, 2H), 1.80-1.10 (m, 21H), 1.05-0.72 (m, 9H). LCMS Rt=1.360min(2分間のクロマトグラフィー)、C28H40N3O2[M+H]+のMS ESI計算値450、実測値450.
化合物120:1H NMR (400 MHz, CDCl3) δ7.88-7.86 (m, 2H), 7.40-7.37(m, 2H), 5.56-5.46 (m, 2H), 2.65 (t, J = 8.8Hz, 1H), 2.21-2.10 (m, 2H), 1.80-1.10 (m, 21H), 1.17-0.74 (m, 9H). LCMS:Rt=1.008min(1.5分間のクロマトグラフィー)、C28H40N3O2[M+H]+のMS ESI計算値450、実測値450.
化合物121:1H NMR (400 MHz, CDCl3) δ7.48-7.47(m, 1H), 6.73-6.72 (m, 1H), 5.05-4.88 (m, 2H), 2.59 (t, J = 8.8Hz, 1H), 2.17-1.95 (m, 2H), 1.80-1.10 (m, 21H), 1.05-0.65 (m, 9H). LCMS Rt=0.949min(1.5分間のクロマトグラフィー)、C26H38N3O2[M+H]+のMS ESI計算値424、実測値406[M+H−18]+.
化合物122:1H NMR (400 MHz, CDCl3) δ7.50-7.44 (m, 1H), 6.77 - 6.71 (m, 1H), 5.12 - 4.86 (m, 2H), 2.78 - 2.72 (m, 1H), 1.94 - 1.10 (m, 58H), 1.06 - 0.69 (m, 15H). LCMS:Rt=1.373min(2分間のクロマトグラフィー)、C26H37N3O2Na[M+Na]+のMS ESI計算値446、実測値446.
化合物124:1H NMR (400 MHz, CDCl3) δ 7.84-7.80 (m, 1H), 7.14-7.10 (m, 1H), 5.44-5.31 (m, 2H), 2.73-2.69 (m, 1H), 2.25-2.05 (m, 2H), 1.80-1.10 (m, 22H), 1.05-0.90 (m, 2H), 0.77 (s, 3H), 0.71 (s, 3H). LCMS Rt=1.404min(2分間のクロマトグラフィー)、C28H38F2N3O2[M+H]+のMS ESI計算値486、実測値486.
化合物125:1H NMR: (400 MHz, CDCl3) δ7.77-7.73 (m, 1H), 7.13 - 7.06 (m, 1H), 5.53-5.40 (m, 2H), 3.90 (s, 3H), 2.72-2.61 (m, 1H), 2.35-2.12 (m, 3H), 1.90-0.72 (m, 30H). LCMS:Rt=1.422min(2分間のクロマトグラフィー)、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
化合物126:1H NMR: (400 MHz, CDCl3) δ7.96-7.87 (m, 1H), 7.01 (dd, J=2.0, 9.0 Hz, 1H), 6.60 (d, J=2.0 Hz, 1H), 5.33 (d, J=5.8 Hz, 2H), 3.86 (s, 3H), 2.76 - 2.65 (m, 1H), 2.28 - 2.10 (m, 2H), 1.83 - 1.12 (m, 21H), 0.75 (d, J=17.6 Hz, 9H). LCMS:Rt=1.362min(2分間のクロマトグラフィー)、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
化合物127:1H NMR: (400 MHz, CDCl3) δ7.95-7.89 (m, 1H), 7.43-7.34 (m, 1H), 7.18 (d, J=17.3 Hz, 2H), 7.0 -6.98 (m, 1H), 6.63-6.58 (m, 1H), 5.59-5.19 (m, 2H), 3.89 (s, 3H), 2.73-2.62 (m, 1H), 2.26-2.07 (m, 2H), 1.82-1.11 (m, 18H), 1.07-0.65 (m, 9H) LCMS:Rt=1.359min(2分間のクロマトグラフィー)、C29H42N3O3[M+H]+のMS ESI計算値480、実測値480.
化合物128:1H NMR (400 MHz, CDCl3) δ 7.67 (d, J=8.8 Hz, 1H), 7.37 - 7.28 (m, 1H), 7.09 - 6.98 (m, 1H), 5.54 (d, J=5.5 Hz, 2H), 2.66 (s, 1H), 2.27 - 2.09 (m, 3H), 1.87 - 1.09 (m, 20H), 0.75 (d, J=11.3 Hz, 9H). LCMS:Rt=1.446min(2分間のクロマトグラフィー)、C28H39FN3O2[M+H]+のMS ESI計算値468、実測値450[M+H−18]+.
化合物129:1H NMR (400 MHz, CDCl3): δ 7.28 (s, 1H), 7.06 (s, 1H), 5.00-4.84 (m, 2H), 2.64 (t, J = 8.4 Hz, 1H), 2.22-2.06 (m, 2H), 1.79-1.53 (m, 4H), 1.50-1.20 (m, 19H), 1.02-0.85 (m, 19H), 0.78 (s, 3H), 0.72 (s, 3H). LCMS:Rt=0.901min(1.5分間のクロマトグラフィー)、C26H37N3O2[M+H]+のMS ESI計算値424、実測値424.
化合物130:1H NMR (400 MHz, CDCl3): δ 7.33 (s, 1H), 7.16 (s, 1H), 4.90-4.77 (m, 2H), 2.56 (t, J = 8.4 Hz, 1H), 2.17-2.08 (m, 5H), 1.72-1.50 (m, 6H), 1.40-1.20 (m, 15H), 0.80-0.79 (m, 3H), 0.75 (s, 3H), 0.70 (s, 3H). LCMS:Rt=0.927min(1.5分間のクロマトグラフィー)、C26H40N2O2[M+H]+のMS ESI計算値413、実測値413.
化合物131:1H NMR (400 MHz, CDCl3): δ 7.72 (s, 2H), 5.02-4.86 (m, 2H), 2.60 (t, J = 8.4 Hz, 1H), 2.19-2.03 (m, 5H), 1.73-1.51 (m, 6H), 1.37-1.20 (m, 16H), 0.85-0.82 (m, 3H), 0.76 (s, 3H), 0.67(s, 3H). LCMS:Rt=0.983min(1.5分間のクロマトグラフィー)、C26H37F3N2O2[M+H]+のMS ESI計算値467、実測値467.
化合物133:1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 18.1 Hz, 1H), 4.94 - 4.76 (m, 1H), 2.61-2.53 (m, 1H), 2.25-2.13 (m, 1H), 2.08-1.80 (m, 3H), 1.79-1.66 (m, 3H), 1.63-1.35 (m, 11H), 1.34-1.18 (m, 9H), 1.17-1.01 (m, 2H), 0.95 (s, 3H), 0.65 (s, 3H). LCMS:Rt=1.127min(2分間のクロマトグラフィー)、C25H37ClN2O2[M+H]+のMS ESI計算値433、実測値433.
化合物134:1H NMR (400 MHz, CDCl3) δ 7.72 (s, 1H), 5.03 - 4.84 (m, 1H), 2.64 - 2.55 (m, 1H), 2.27 - 1.02 (m, 28H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS:Rt=1.332min(2分間のクロマトグラフィー)、C26H37F3N2O2[M+H]+のMS ESI計算値467、実測値467.
化合物135:1H NMR (400 MHz, CDCl3) δ 7.29 (s, 1H), 6.55 (s, 1H), 4.66-4.54 (m, 2H), 2.55 (t, J = 8.4 Hz, 1H), 2.27-2.00 (m, 5H), 1.70-1.51 (m, 5H), 1.47-1.21 (m, 18H), 0.84-0.80 (m, 3H), 0.76 (s, 3H), 0.65(s, 3H). LCMS:Rt=0.795min(1.5分間のクロマトグラフィー)、C26H40N2O2[M+H]+のMS ESI計算値413、実測値413.
化合物136:1H NMR (400 MHz, DMSO-d6) δ 7.42 (s, 1H), 6.62(s, 1H), 5.03-4.77 (m, 2H), 3.88 (s, 1H), 2.68 (t, J = 10 Hz, 3H), 2.34 (s, 1H) 2.04-1.63 (m, 5H), 1.44-1.15 (m, 27H), 1.07-0.75 (m, 4H), 0.72 (s, 3H), 0.59(s, 3H). LCMS:Rt=1.087min(1.5分間のクロマトグラフィー)、C26H40N2O2[M+H]+のMS ESI計算値413、実測値413.
化合物137:1H NMR (400 MHz, CDCl3) δ 7.45 (s, 1H), 7.41 (s, 1H), 4.93-4.78 (m, 2H), 2.57 (t, J = 8.8 Hz, 1H), 2.18-2.04 (m, 2H), 1.73-1.50 (m, 4H), 1.27-1.17 (m, 18H), 0.81-0.80 (m, 3H) 0.75 (s, 3H), 0.66(s, 3H). LCMS:Rt=0.953min(1.5分間のクロマトグラフィー)、C25H37ClN2O2[M+Na]+のMS ESI計算値433、実測値433.
化合物138:1H NMR (400 MHz, CDCl3) δ 7.43 (d, J=6.0 Hz, 1H), 4.79 - 4.68 (m, 1H), 2.65 - 2.53 (m, 1H), 2.20 (d, J=9.3 Hz, 1H), 2.04 - 1.02 (m, 29H), 0.96 (s, 3H), 0.70 - 0.59 (m, 3H). LCMS:Rt=0.891min(1.5分間のクロマトグラフィー)、C26H37N3O2[M+H]+のMS ESI計算値424、実測値424.
化合物140(64.3mg):1HNMR (クロロホルム-d, 400MHz) δ = 7.72 (s, 2H), 4.86-5.02 (m, 2H), 3.33-3.43 (m, 3H), 3.19 (s, 2H), 2.61 (t, J=8.8 Hz, 1H), 2.16-2.25 (m, 1H), 1.99-2.08 (m, 2H), 1.63-1.78 (m, 4H), 1.06-1.55 (m, 14H), 0.94-1.03 (m, 1H), 0.82-0.89 (m, 1H), 0.72-0.80 (m, 3H), 0.67 (s, 3H). LCMS:Rt=3.106min(4分間のクロマトグラフィー)、C27H39F3N2O3[M+H]+のMS ESI計算値497.3、実測値497.1([M+H]+).
化合物141(59.4mg):1HNMR (クロロホルム-d, 400MHz): δ = 9.65 (br. s., 1H), 7.32 (s, 1H), 7.06 (s, 1H), 5.44 (d, J=17.6 Hz, 1H), 5.26 (d, J=18.2 Hz, 1H), 3.39 (s, 3H), 3.19 (s, 2H), 2.72 (t, J=9.0 Hz, 1H), 2.20 (d, J=10.6 Hz, 1H), 2.11 (d, J=11.6 Hz, 2H), 1.49-1.80 (m, 10H), 1.22-1.42 (m, 8H), 0.94-1.04 (m, 1H), 0.85 (t, J=9.6 Hz, 1H), 0.76 (s, 3H), 0.69 (s, 3H). LCMS:Rt=2.074min(4分間のクロマトグラフィー)、C26H40N2O3[M+Na]+のMS ESI計算値451.3、実測値451.2([M+Na]+.
化合物141(59.4mg):1HNMR (クロロホルム-d, 400MHz) δ = 7.86 (s, 1H), 7.82 (s, 1H), 4.87-5.05 (m, 2H), 3.40 (s, 3H), 3.19 (s, 2H), 2.61 (t, J=8.8 Hz,1H),2.16-2.26 (m, 1H), 2.01-2.08 (m, 2H), 1.66-1.77 (m, 4H), 1.14-1.55 (m, 14H), 0.94-1.04 (m, 1H), 0.82-0.89 (m, 1H), 0.76 (s, 3H), 0.66 (s, 3H). LCMS Rt=2.827min(4分間のクロマトグラフィー)、C27H39N3O3[M+H]+のMS ESI計算値454.3、実測値454.2([M+H]+.
化合物143:1H NMR (400 MHz, CDCl3) δ 7.25 (d, J=1.0 Hz, 1H), 7.04 (d, J=1.0 Hz, 1H), 5.00 - 4.81 (m, 2H), 2.69 - 2.57 (m, 1H), 2.29 - 1.02 (m, 27H), 0.99 - 0.89 (m, 3H), 0.69 (s, 3H). LCMS:Rt=1.367min(2分間のクロマトグラフィー)、C27H42N2O3[M+H+Na]+のMS ESI計算値424、実測値424.
化合物145:1H NMR (400 MHz, CDCl3) δ 7.28 (s,1H), 7.07 (s, 1H), 4.86-4.73 (m, 2H), 3.97-3.92 (m, 2H), 2.54 (t, J = 8.8 Hz, 1H), 2.19-1.70 (m, 9H), 1.43-1.07 (m, 22H), 0.94 (s, 3H), 0.65 (s, 3H). LCMS:Rt=0.918min(1.5分間のクロマトグラフィー)、C27H42N2O3[M+H]+のMS ESI計算値443、実測値443.
化合物146:1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 8.08 (s, 1H), 5.05 - 4.83 (m, 2H), 2.67 - 2.55 (m, 1H), 2.28 - 1.01 (m, 28H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS:Rt=1.330min(2分間のクロマトグラフィー)、C25H37N3O4[M+H−H2O]+のMS ESI計算値426、実測値426.
化合物147:1H NMR (400 MHz, CDCl3) δ 7.34 (s, 1H), 7.16 (s, 1H), 4.91 - 4.75 (m, 2H), 2.60 - 2.49 (m, 1H), 2.27 - 1.00 (m, 31H), 0.94 (s, 3H), 0.65 (s, 3H). LCMS Rt=1.264min(2分間のクロマトグラフィー)、C26H40N2O2[M+H]+のMS ESI計算値413、実測値413.
化合物148:1H NMR (400 MHz, CDCl3) δ 7.27 (s, 1H), 7.07 (s, 1H), 4.86-4.72 (m, 2H), 3.75 (s, 3H), 2.55 (t, J = 9.2 Hz, 1H), 2.22-2.17 (m, 2H), 1.72-1.50 (m, 4H), 1.37-1.20 (m, 17H),0.80-0.79 (m, 3H) 0.75 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.306min(2分間のクロマトグラフィー)、C26H40N2O3[M+Na]+のMS ESI計算値429、実測値429.
化合物149:1H NMR (400 MHz, CDCl3) δ 7.24 (s, 1H), 7.05 (d, J = 6.8 Hz, 1H), 4.83-4.69 (m, 2H), 3.94-3.89 (m, 2H), 2.53 (t, J = 8.8 Hz, 1H), 2.17-1.99 (m, 2H), 1.67-1.18 (m, 24H), 0.78-0.77 (m, 3H) 0.73 (s, 3H), 0.64 (s, 3H). LCMS Rt=1.334min(2分間のクロマトグラフィー)、C27H42N2O3[M+Na]+のMS ESI計算値443、実測値443.
化合物149:1H NMR (400 MHz, CDCl3) δ 7.25 (s, 1H), 7.06 (s, 1H), 4.84-4.71 (m, 2H), 4.14-4.13 (m, 1H), 2.54 (t, J = 8.8 Hz, 1H), 2.18-2.00 (m, 2H), 1.69-1.50 (m, 24H), 1.36-1.19 (m, 22H), 0.79-0.78 (m, 2H) 0.74 (s, 3H), 0.65 (s, 3H). LCMS Rt=0.957min(1.5分間のクロマトグラフィー)、C28H44N2O3[M+Na]+のMS ESI計算値479、実測値479.
化合物151:1H NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 8.08 (s, 1H), 5.03-4.86 (m, 2H), 2.61 (t, J = 8.8 Hz, 1H), 2.20-2.05 (m, 2H), 1.75-1.51 (m, 4H), 1.50-1.21 (m, 16H), 0.99-0.82 (m, 2H) 0.76 (s, 3H), 0.66 (s, 3H). LCMS Rt=0.940min(1.5分間のクロマトグラフィー)、C25H37N3O4[M+H−H2O]+のMS ESI計算値426、実測値426.
化合物154:1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 6 Hz, 1H), 4.79-4.69 (m, 2H), 2.59 (t, J = 8.8 Hz, 1H), 2.21-1.92 (m, 2H), 1.72-1.50 (m, 4H), 1.38-1.21 (m, 22H), 0.85-0.83 (m, 4H), 0.76 (s, 3H), 0.65 (s, 3H). LCMS Rt=0.888min(1.5分間のクロマトグラフィー)、C26H37N3O2[M+H]+のMS ESI計算値424、実測値424.
A56の合成。ブロモトリフェニル(プロピル)ホスホラン(11.6g、30.3mmol)の無水THF(160mL)中の懸濁物に、カリウム2−メチルプロパン−2−オレート(3.40g、30.3mmol)を、N2雰囲気下25℃で添加した。得られた混合物を65℃で1時間撹拌し、この時点で、無水THF(40mL)中のA50(3.1g、10.1mmol)を65℃で添加した。この混合物を65℃で16時間撹拌し、この時点で、TLC(PE:EA=2:1)は、出発物質が消費されたことを示した。反応を水(100mL)でクエンチし、そして酢酸エチル(150mL×3)で抽出し、そして合わせた有機相をブライン(150mL)で洗浄し、Na2SO4で乾燥させ、そして濃縮して残渣を得、これをシリカゲルでのクロマトグラフィー(PE:EtOAc=6:1)により精製して、A56(2.2g)を白色固体として得た。1H NMR (400 MHz, CDCl3) δ 5.09 - 4.90 (m, 1H), 2.37 (dd, J=6.8, 16.3 Hz, 1H), 2.24 - 1.99 (m, 4H), 1.77 - 1.10 (m, 23H), 1.04 - 0.67 (m, 13H).
化合物158(34mg):1H NMR (400 MHz, CDCl3) δ 7.32 (s, 1H), 7.12 (s, 1H), 4.81-4.97 (m, 2H), 3.70-3.84 (m, 3H), 3.39 (s, 3H), 3.19 (s, 2H), 2.58 (t, J=8.7 Hz, 1H), 2.13-2.25 (m, 1H), 2.05 (d, J=11.3 Hz, 1H), 1.62-1.77 (m, 4H), 1.11-1.61 (m, 15H), 0.94-1.03 (m, 1H), 0.80-0.88 (m, 1H), 0.76 (s, 3H), 0.67 (s, 3H). LCMS:Rt=2.776min(4分間のクロマトグラフィー)、C27H42N2O4[M+H]+のMS ESI計算値459.3、実測値459.2[M+H]+.
化合物159(33.2mg):1H NMR (DMSO-d6, 400MHz): δ = 7.36 (s, 1H), 7.18 (s, 1H), 4.80-5.00 (m, 2H), 4.01 (s, 1H), 3.86 (q, J=7.0 Hz, 2H), 3.24 (s, 3H), 3.03 (s, 2h), 2.59-2.67 (m, 1H), 2.33 (br. s., 1H), 2.01 (d, J=11.0 Hz, 2H), 1.62 (br. s., 4H), 1.17-1.54 (m, 12H), 1.15 (d, J=10.0 Hz, 4H), 1.04 (d, J=13.2 Hz, 1H), 0.82-0.95 (m, 1H), 0.69 (s, 3H), 0.55 (s, 3H). LCMS:Rt=2.869min(4分間のクロマトグラフィー)、C28H44N2O4[M+H]+のMS ESI計算値473.3、実測値473.6([M+H]+.
A61の合成。K2CO3(937mg、6.78mmol)を、アセトン(15mL)中のA55(1.5g、3.39mmol)およびエチル1H−ピラゾール−4−カルボキシレート(616mg、4.4mmol)に25℃で添加した。得られた混合物を25℃で12時間撹拌し、この時点で、TLCは、反応が完了したことを示した。この反応混合物を水(50mL)で希釈し、次いで、EtOAc(50mL×3)で抽出し、そして合わせた有機層をブライン(50mL)で洗浄した。その有機層を、Na2SO4で乾燥させ、濾過し、そしてクロマトグラフィー(シリカゲル:PE中EtOAc20〜50%)により精製して、A61(1.4g、82.8%)を白色固体として得た。1H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.91 (s, 1H), 4.81-5.04 (m, 2H), 4.28-4.33 (m, 2H), 3.33-3.46 (m, 3H), 3.12-3.24 (m, 2H), 2.60 (t, J=8.8 Hz, 1H), 2.15-2.26 (m, 1H), 1.63-1.76 (m, 4H), 1.15-1.55 (m, 19H), 0.99 (td, J=12.2, 4.8 Hz, 1H), 0.82-0.89 (m, 1H), 0.74-0.79 (m, 3H), 0.47-0.73 (m, 3H). LCMS:Rt=0.911min(1.5分間のクロマトグラフィー)、C29H44N2O5[M+H]+のMS ESI計算値501.3、実測値501.7([M+H]+.
化合物162(83.2mg):1H NMR (CDCl3, 400MHz): δ 7.72-7.81 (m, 2H), 4.84-5.00 (m, 2H), 3.39 (s, 3H), 3.18 (s, 8H), 2.60 (t, J=8.6 Hz, 1H), 2.15-2.24 (m, 1H), 2.05 (d, J=11.6 Hz, 1H), 1.62-1.78 (m, 5H), 1.13-1.56 (m, 14H), 0.94-1.03 (m, 1H), 0.80-0.88 (m, 1H), 0.76 (s, 3H), 0.67 ppm (s, 3H). LCMS Rt=2.572min(4分間のクロマトグラフィー)、C29H45N3O4[M+H]+のMS ESI計算値500.3、実測値500.2([M+H]+.
化合物163(102mg):1H NMR (CDCl3, 400MHz): δ 7.89 (br. s., 1h), 7.80 (br. s., 1H), 5.78 (br. s., 2H), 4.94 (d, J=19.2 Hz, 2H), 3.39 (s, 3H), 3.19 (s, 2h), 2.61 (br. s., 1H), 2.19 (br. s., 1h), 2.01-2.07 (m, 1H), 1.90 (br. s., 2H), 1.63-1.82 (m, 4H), 1.12-1.60 (m, 13H), 0.98 (d, J=11.6 Hz, 1H), 0.84 (t, J=9.8 Hz, 1H), 0.76 (s, 3H), 0.66 (br. s., 3H). LCMS:Rt=2.293min(4分間のクロマトグラフィー)、C27H41N3O4[M+H]+のMS ESI計算値472.3、実測値472.2([M+H]+.
化合物164(8.2mg):1H NMR (CDCl3, 400MHz): δ 7.25 (s, 1H), 7.05 (s, 1H), 4.82-5.00 (m, 2H), 3.40 (s, 3H), 3.19 (s, 2H), 2.63 (t, J=8.4 Hz, 1H), 2.18-2.27 (m, 1H), 2.07 (d, J=11.6 Hz, 1H), 1.65-1.78 (m, 4H), 1.09-1.58 (m, 15H), 0.96-1.05 (m, 1H), 0.86 (t, J=9.8 Hz, 1H), 0.76 (s, 3H), 0.71 (s, 3H). LCMS:Rt=2.760min(4分間のクロマトグラフィー)、C27H39N3O3[M+H]+のMS ESI計算値454.4、実測値454.1([M+H]+.
化合物165(15.6mg):1H NMR (CDCl3, 400MHz): δ 7.87 (s, 1H), 7.82 (d, J=9.0 Hz, 1H), 7.35 (dd, J=9.0, 2.0 Hz, 1H), 5.44-5.55 (m, 2H), 3.40 (s, 3H), 3.19 (s, 2H), 2.66 (t, J=8.6 Hz, 1H), 2.18-2.28 (m, 1H), 2.14 (d, J=11.6 Hz, 1H), 2.02 (br. s., 1H), 1.65-1.81 (m, 4H), 1.12-1.54 (m, 14H), 0.95-1.04 (m, 1H), 0.82-0.89 (m, 1H), 0.77 (s, 3H), 0.73 ppm (s, 3H). LCMS:Rt=3.012min(4分間のクロマトグラフィー)、C29H40ClN3O3[M+H]+のMS ESI計算値514.2、実測値514.1([M+H]+.
化合物166:1H NMR (CDCl3, 400MHz): δ 7.28 (s, 1H), 7.08 (s, 1H), 4.87 - 4.71 (m, 2H), 3.76 (s, 3H), 2.55 (t, J=8.9 Hz, 1H), 2.25 - 1.01 (m, 31H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS:Rt=1.263min(2分間のクロマトグラフィー)、C26H40N2O3[M+H]+のMS ESI計算値429、実測値429.
化合物167:1H NMR (MeOD, 400MHz): δ 8.07 (s, 1H), 7.93 (s, 1H), 5.11 (d, J=4.3 Hz, 2H), 2.79 - 2.72 (m, 1H), 2.27 - 1.06 (m, 27H), 1.00 (s, 3H), 0.69 (s, 3H). LCMS:Rt=1.166min(1.5分間のクロマトグラフィー)、C26H39N3O3[M+H−H2O]+のMS ESI計算値424、実測値424.
化合物168:1H NMR (CDCl3, 400MHz): Δ 8.01 - 7.76 (m, 2h), 6.10 (br. s., 1h), 4.96 (br. s., 2h), 2.97 (br. s., 3H), 2.60 (br. s., 1H), 2.28 - 1.00 (m, 31H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS:Rt=0.818min(1.5分間のクロマトグラフィー)、C26H40N2O3[M+H−H2O]+のMS ESI計算値438、実測値438.
化合物169:1H NMR (CDCl3, 400MHz): δ7.80 - 7.72 (m, 1H), 5.05 - 4.81 (m, 1H), 3.12 (br. s., 3H), 2.71 - 2.53 (m, 1H), 2.26 - 0.99 (m, 28H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS:Rt=1.194min(2分間のクロマトグラフィー)、C28H43N3O3[M+H−H2O]+のMS ESI計算値452、実測値452.
化合物172:1H NMR (CDCl3, 400MHz): δ7.30 (br. s., 1H), 6.54 (s, 1H), 4.67 - 4.51 (m, 2H), 2.54 (t, J=8.8 Hz, 1H), 2.28 - 1.00 (m, 32H), 0.95 (s, 3H), 0.64 (s, 3H).
LCMS Rt=1.072min(1.5分間のクロマトグラフィー)、5−95AB、C26H40N2O2[M+H]+のMS ESI計算値413、実測値413.
化合物173:1H NMR (CDCl3, 400MHz): δ7.07 (br. s., 1H), 4.89 - 4.64 (m, 2H), 4.17 (td, J=6.0, 12.0 Hz, 1H), 2.65 - 2.47 (m, 1H), 2.25 - 1.00 (m, 31H), 0.94 (s, 3H), 0.75 - 0.56 (m, 3H). LCMS Rt=1.338min(2分間のクロマトグラフィー)、C28H44N2O3[M+H]+のMS ESI計算値457、実測値457.
化合物174:1H NMR (CDCl3, 400MHz): δ7.23 (br. s., 1H), 6.99 - 6.97 (m, 1H), 7.00 (br. s., 1H), 5.12 - 4.77 (m, 2H), 2.65 (br. s., 3H), 2.27 - 1.01 (m, 28H), 0.99 - 0.87 (m, 3H), 0.66 (s, 3H). LCMS:Rt=1.065min(2分間のクロマトグラフィー)、C26H40N2O2[M+H]+のMS ESI計算値413、実測値413.
化合物175:1H NMR (CDCl3, 400MHz): δ7.56 (d, J = 2 Hz, 1H), 7.48 (s, 1H), 5.37-5.10 (m, 2H), 3.86 (s, 1H), 2.74 (t, J = 8.8 Hz, 1H), 2.41 (s, 3H), 2.32-2.03 (m, 3H), 1.72-1.10 (m, 20H), 1.05-0.74 (m, 2H), 0.70 (s, 3H), 0.58 (s, 3H). LCMS Rt=0.775min(1.5分間のクロマトグラフィー)、C26H40N2O2[M+H]+のMS ESI計算値413、実測値413.
化合物176:1H NMR (CDCl3, 400MHz): δ7.56 (s, 1H), 7.43 (s, 1H), 4.99-4.86 (m, 2H), 4.61 (s, 3H), 2.59 (t, J = 9.2 Hz, 1H), 2.17-2.04 (m, 3H), 1.54-1.20 (m, 19H), 0.98-0.81 (m, 3H), 0.75 (s, 1H), 0.66 (s, 1H). LCMS Rt=1.200min(2分間のクロマトグラフィー)、C26H40N2O3[M+H]+のMS ESI計算値429、実測値429.
化合物177:1H NMR (CDCl3, 400MHz): δ7.88 (s, 1H), 7.79 (s, 1H), 5.54 (s, 2H), 5.01-4.85 (m, 2H), 2.60 (t, J = 8.4 Hz, 1H), 2.24-2.02 (m, 2H), 1.72-1.51 (m, 4H), 1.41-1.21 (m, 2H), 0.98-0.82 (m, 2H), 0.76 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.172min(2分間のクロマトグラフィー)、C26H39N3O3[M+H]+のMS ESI計算値442、実測値442.
化合物178:1H NMR (CDCl3, 400MHz): δ7.86 (s, 1H), 7.82 (s, 1H), 4.87-5.05 (m, 2H), 3.40 (s, 3H), 3.19 (s, 2H), 2.61 (t, J=8.8 Hz,1H),2.16-2.26 (m, 1H), 2.01-2.08 (m, 2H), 1.66-1.77 (m, 4H), 1.14-1.55 (m, 14H), 0.94-1.04 (m, 1H), 0.82-0.89 (m, 1H), 0.76 (s, 3H), 0.66 (s, 3H). LCMS:Rt=2.827min(4分間のクロマトグラフィー)、C27H39N3O3[M+H]+のMS ESI計算値454.3、実測値454.2([M+H]+.
化合物179:1H NMR (CDCl3, 400MHz): δ7.26 - 7.25 (m, 1H), 7.07 (s, 1H), 4.78 (d, J=19.6 Hz, 2H), 4.21 - 4.13 (m, 1H), 3.39 (s, 3H), 3.18 (s, 2H), 2.58 - 2.52 (m, 1H), 2.23 - 2.12 (m, 1H), 2.06 - 1.97 (m, 2H), 1.69 (d, J=3.3 Hz, 5H), 1.59 - 1.49 (m, 4H), 1.49 - 1.35 (m, 4H), 1.31 (d, J=6.0 Hz, 11H), 1.25 - 1.12 (m, 4H), 1.02 - 0.91 (m, 1H), 0.87 - 0.79 (m, 1H), 0.75 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.046min(2分間のクロマトグラフィー)、C29H46N2O4[M+H]+のMS ESI計算値487、実測値487.
化合物183:1H NMR (CDCl3, 400MHz): δ7.35 (s, 1H), 5.03-5.21 (m, 2H), 3.39 (s, 3H), 3.19 (s, 2H), 2.63 (t, J=8.8 Hz, 1H), 2.38 (s, 3H), 2.15-2.25 (m, 1H), 1.99-2.10 (m, 2H), 1.63-1.77 (m, 4H), 1.10-1.58 (m, 14H), 0.95-1.04 (m, 1H), 0.81-0.89 (m, 1H), 0.76 (s, 3H), 0.66 (s, 3H). LCMS Rt=2.657min(4分間のクロマトグラフィー)、C26H41N3O3[M+H]+のMS ESI計算値444.3、実測値444.1([M+H]+.
化合物184:1H NMR (DMSO-d6, 400MHz): δ7.49 (s, 1H), 5.46 (d, J=18.6 Hz, 1H), 5.23 (d, J=18.6 Hz, 1H), 4.02 (s, 1H), 3.24 (s, 3H), 3.04 (s, 2H), 2.80 (t, J=9.0 Hz, 1h), 2.67 (br. s., 1H), 2.33 (br. s., 1H), 2.13 (s, 3H), 2.04 (d, J=8.0 Hz, 1H), 1.64 (d, J=16.6 Hz, 4H), 1.49 (d, J=9.0 Hz, 13H), 0.93 (d, J=9.6 Hz, 1H), 0.76 (d, J=9.6 Hz, 1H), 0.70 (s, 3H), 0.58 (s, 3H). LCMS Rt=2.683min(4分間のクロマトグラフィー)、C26H41N3O3[M+H]+のMS ESI計算値444.3、実測値444.1([M+H]+.
化合物185:1H NMR (CDCl3, 400MHz): δ8.00 (d, J=9.6 Hz, 1H), 7.29-7.38 (m, 2H), 5.38 (q, J=18.2 Hz, 2H), 3.40 (s, 3H), 3.19 (s, 2H), 2.73 (t, J=8.6 Hz, 1H), 2.13-2.26 (m, 2H), 2.03 (s, 1H), 1.67-1.82 (m, 4H), 1.13-1.56 (m, 14H), 0.97-1.06 (m, 1H), 0.84-0.91 (m, 1H), 0.78 (s, 3H), 0.72 (s, 3H). LCMS Rt=3.150min(4.0分間のクロマトグラフィー)、C29H40ClN3O3[M+H]+のMS ESI計算値514.1、実測値514.1([M+H]+.
化合物186:1H NMR (CDCl3, 400MHz): δ8.01 (s, 1H), 7.66 (d, J=8.6 Hz, 1H), 7.20 (s, 1H), 7.08-7.16 (m, 1H), 5.04-5.16 (m, 2H), 3.39 (s, 3H), 3.19 (s, 2H), 2.65 (t, J=9.0 Hz, 1H), 2.10-2.24 (m, 2H), 2.01 (s, 1H), 1.66-1.75 (m, 4H), 1.13-1.54 (m, 14H), 0.94-1.03 (m, 1H), 0.82-0.90 (m, 1H), 0.77 (s, 3H), 0.71 (s, 3H). LCMS Rt=3.269min(4.0分間のクロマトグラフィー)、C30H41ClN2O3[M+H]+のMS ESI計算値513.3、実測値513.0([M+H]+.
化合物187:1H NMR (CDCl3, 400MHz): δ7.43 (s, 1H), 5.15 (d, J=4.6 Hz, 2H), 3.40 (s, 3H), 3.19 (s, 2H), 2.58 (t, J=8.8 Hz, 1H), 2.34 (s, 3H), 2.15-2.23 (m, 1H), 2.00-2.09 (m, 2H), 1.63-1.76 (m, 4H), 1.09-1.56 (m, 14H), 0.94-1.03 (m, 1H), 0.81-0.87 (m, 1H), 0.76 (s, 3H), 0.70 ppm (s, 3H). LCMS:Rt=2.873min(4.0分間のクロマトグラフィー)、C26H41N3O3[M+H]+のMS ESI計算値444.3、実測値444.2([M+H]+.
化合物188:1H NMR (CDCl3, 400MHz): δ7.30 (s, 1H), 6.56 (s, 1H), 4.55-4.67 (m, 2H), 3.39 (s, 3H), 3.19 (s, 2H), 2.56 (t, J=8.8 Hz, 1H), 2.23 (s, 3H), 2.13-2.21 (m, 1H), 2.00-2.08 (m, 1H), 1.95 (d, J=11.6 Hz, 1H), 1.66-1.75 (m, 4H), 1.14-1.58 (m, 14H), 0.94-1.04 (m, 1H), 0.81-0.88 (m, 1H), 0.76 (s, 3H), 0.65 (s, 3H). LCMS:Rt=2.194min(4.0分間のクロマトグラフィー)、C27H42N2O3[M+H]+のMS ESI計算値443.3、実測値443.2([M+H]+.
化合物189:1H NMR (CDCl3, 400MHz): δ7.54 (s, 1H), 7.41 (s, 1H), 4.96-4.82 (m, 1H), 4.61 (s, 3H), 3.39 (s, 3H), 3.18 (s, 3H), 2.59 (t, J=8.8 Hz, 1H), 2.20-2.01 (m, 4H), 1.71-1.22 (m, 22H), 0.99-0.84 (m, 2H), 0.75 (s, 3H), 0.66 (s, 3H). LCMS Rt=0.818min(1.5分間のクロマトグラフィー)、C27H42N2O4[M+Na]+のMS ESI計算値481、実測値481.
化合物190:1H NMR (CDCl3, 400MHz): δ7.54 (s, 1H), 7.42 (s, 1H), 4.96-4.82 (m, 1H), 4.61 (s, 3H), 2.58 (t, J=8.8 Hz, 1H), 2.07-1.71 (m, 8H), 1.57-1.11 (m, 23H), 0.95 (s, 1H), 0.66 (s, 1H). LCMS Rt=0.823min(1.5分間のクロマトグラフィー)、C26H40N2O3[M+H]+のMS ESI計算値429、実測値429.
化合物191:1H NMR (CDCl3, 400MHz): δ 7.90 (s, 1H), 7.71 - 7.61 (m, 2H), 7.23 (dd, J=2.0, 9.0 Hz, 1H), 5.28 - 5.12 (m, 2H), 3.41 (s, 3H), 3.21 (s, 2H), 2.66 (t, J=8.7 Hz, 1H), 2.29 - 2.18 (m, 1H), 2.12 (d, J=12.0 Hz, 1H), 2.03 (s, 1H), 1.81 - 1.67 (m, 4H), 1.57 (br. s., 2H), 1.50 - 1.36 (m, 4H), 1.35 - 1.17 (m, 8H), 1.05 - 0.96 (m, 1H), 0.91 - 0.84 (m, 1H), 0.78 (s, 3H), 0.72 (s, 3H). LCMS Rt=1.217min(2分間のクロマトグラフィー)、C30H41ClN2O3[M+H]+のMS ESI計算値513、実測値513.
化合物193:1H NMR (CDCl3, 400MHz): δ5.20 - 5.03 (m, 1H), 3.41 (s, 3H), 3.21 (s, 2H), 2.72 - 2.64 (m, 1H), 2.49 (s, 3H), 2.27 - 2.17 (m, 1H), 2.11 - 2.05 (m, 1H), 2.04 (s, 1H), 1.84 - 1.67 (m, 1H), 1.66 - 1.60 (m, 1H), 1.57 - 1.15 (m, 13H), 1.08 - 0.94 (m, 1H), 0.94 - 0.84 (m, 1H), 0.79 (s, 3H), 0.69 (s, 3H). LCMS Rt=0.999min(2分間のクロマトグラフィー)、C25H40N4O3[M+H]+のMS ESI計算値445、実測値445.
化合物194:1H NMR (CDCl3, 400MHz): δ5.45 - 5.29 (m, 2H), 3.41 (s, 3H), 3.20 (s, 2H), 2.65 (t, J=8.8 Hz, 1H), 2.58 (s, 3H), 2.29 - 2.18 (m, 1H), 2.13 - 1.99 (m, 2H), 1.83 - 1.66 (m, 4H), 1.58 - 1.14 (m, 14H), 1.06 - 0.94 (m, 1H), 0.92 - 0.82 (m, 1H), 0.78 (s, 3H), 0.72 (s, 3H)LCMS:Rt=1.056min(2分間のクロマトグラフィー)、C25H40N4O3[M+H]+のMS ESI計算値445、実測値445.
化合物195:1H NMR (CDCl3, 400MHz): δ7.24 (S, 1H), 6.95 (br. s., 1H), 5.05 - 4.73 (m, 2H), 3.41 (s, 3H), 3.20 (s, 2h), 2.68 (br. s., 3h), 2.20 (br. s., 1H), 1.96 (br. s., 1H), 1.90 - 1.63 (m, 6H), 1.59 - 1.16 (m, 14H), 1.06 - 0.95 (m, 1H), 0.93 - 0.82 (m, 1H), 0.77 (s, 3H), 0.68 (s, 3H). LCMS Rt=0.681min(2分間のクロマトグラフィー)、C27H42N2O3[M+H]+のMS ESI計算値443、実測値443.
化合物197:1H NMR (CDCl3, 400MHz): δ7.77 (s, 1H), 7.62 (s, 1H), 5.24-5.08 (m, 2H), 2.85-2.82 (m, 1H), 2.58-2.45 (m, 2H), 2.30-2.20 (m, 2H), 1.95-1.15 (m, 20H), 0.97 (s, 3H), 0.65 (s, 3H). LCMS Rt=1.142min(2分間のクロマトグラフィー)、C24H36N3O3[M+H]+のMS ESI計算値414、実測値414.
化合物198:1H NMR (CDCl3, 400MHz): δ7.68 (s, 2H), 5.23-5.13 (m, 2H), 2.76-2.71 (m, 1H), 2.61-2.40 (m, 2H), 2.30-2.20 (m, 2H), 1.95-1.15 (m, 20H), 0.96 (s, 3H), 0.67 (s, 3H). LCMS Rt=1.180min(2分間のクロマトグラフィー)、C24H36N3O3[M+H]+のMS ESI計算値420、実測値420.
化合物199:1H NMR (CDCl3, 400MHz): δ7.93 (s, 1H), 7.68 (s, 1H), 7.60 (d, J=9.0 Hz, 1H), 7.04 (d, J=7.6 Hz, 1H), 5.10-5.26 (m, 2H), 3.39 (s, 3H), 3.13-3.25 (m, 2H), 2.59-2.71 (m, 1H), 2.17-2.26 (m, 1H), 2.11 (d, J=12.0 Hz, 1H), 2.02 (br. s., 1H), 1.65-1.76 (m, 4H), 1.06-1.55 (m, 14H), 0.93-1.03 (m, 1H), 0.82-0.89 (m, 1H), 0.77 (s, 3H), 0.70 (s, 3H). LCMS Rt=3.190min(4.0分間のクロマトグラフィー)、C30H44O3[M+H]+のMS ESI計算値513.11、実測値513.1([M+H]+.
A72の合成:1H NMR (CDCl3, 400MHz): δ7.00 (s, 1H), 6.33-6.41 (m, 1H), 4.52-4.64 (m, 2H), 3.34-3.41 (m, 3H), 3.06-3.25 (m, 3H), 2.56 (t, J=8.8 Hz, 1H), 2.13-2.25 (m, 1H), 2.01 (s, 1H), 1.90-1.96 (m, 1H), 1.64-1.75 (m, 4H), 1.15-1.50 (m, 13H), 0.93-1.01 (m, 1H), 0.81-0.89 (m, 1H), 0.73-0.79 (m, 3H), 0.65 (s, 3H). LCMS S Rt=1.942min(4.0分間のクロマトグラフィー)、C26H39FN2O3[M+H]+のMS ESI計算値447、実測値447.
化合物202:1H NMR (CDCl3, 400MHz): δ0.66 (s, 3 H), 0.75 (s, 3 H), 0.78-1.03 (m, 3 H), 1.55 (s, 27 H), 2.00 (s, 1 H), 2.04 (br. s., 1 H), 2.03-2.03 (m, 1 H), 2.13-2.23 (m, 1 H), 2.57 (t, J = 8.78 Hz, 1 H), 3.18 (s, 2 H), 3.39 (s, 3 H), 4.82 (s, 1 H), 4.87-4.94 (m, 1 H), 7.38-7.43 (m, 1 H), 7.45 (s, 1 H). LCMS Rt=1.283min(2.0分間のクロマトグラフィー)、C24H36N2O2[M+H]+のMS ESI計算値463、実測値463.
化合物203:1H NMR (CDCl3, 400MHz): δ7.00 (s, 1 H), 6.37 (dd, J = 8.16, 1.63 Hz, 1 H), 4.48-4.68 (m, 2 H), 2.56 (t, J = 8.78 Hz, 1 H), 2.13-2.30 (m, 1 H), 1.89-1.98 (m, 1 H), 1.63-1.81 (m, 4 H), 1.10-1.61 (m, 18 H), 0.89-1.03 (m, 1 H), 0.71-0.86 (m, 4 H), 0.65 (s, 3 H). LCMS:C25H37FN2O2[M+H]+)のMS計算値417;実測値:417.
化合物204:1H NMR (CDCl3, 400MHz): δ7.92 (d, J = 8.8 Hz, 2H), 5.01-4.82 (m, 2H), 4.29 (q, J = 7.3 Hz, 2H), 2.63-2.55 (m, 1H), 2.26-2.14 (m, 1H), 2.06 (d, J = 11.0 Hz, 1H), 1.96 (t, J = 13.2 Hz, 1H), 1.90-1.80 (m, 1H), 1.79-1.68 (m, 3H), 1.53-1.38 (m, 8H), 1.37-1.31 (m, 4H), 1.30-1.20 (m, 8H), 1.18-1.00 (m, 2H), 0.95 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.088min(2分間のクロマトグラフィー)、C28H42N2O4[M+H]+のMS ESI計算値471、実測値471.
化合物205:1H NMR (CDCl3, 400MHz): δ5.17-5.04 (m, 2H), 2.68-2.64 (m, 1H), 2.47 (s, 3H), 2.06-2.04 (m, 2H), 1.76-1.24 (m, 23H), 0.84-0.83 (m, 2H), 0.76 (s, 3H), 0.67 (s, 3H). LCMS Rt=1.241min(2.0分間のクロマトグラフィー)、C24H38N4O2[M+H]+のMS ESI計算値415、実測値415.
化合物206:1H NMR (CDCl3, 400MHz): δ5.40-5.31 (m, 2H), 2.65-2.56 (m, 1H), 2.24 (s, 3H), 2.08-2.06 (m, 2H), 1.76-1.24 (m, 23H), 0.84-0.83 (m, 2H), 0.76 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.290min(2.0分間のクロマトグラフィー)、C24H38N4O2[M+H]+のMS ESI計算値415、実測値415.
化合物207:1H NMR (CDCl3, 400MHz): δ7.69 (s, 2H), 5.30 - 5.17 (m, 2H), 2.61 - 2.52 (m, 1H), 2.26 - 1.01 (m, 31H), 0.95 (s, 3H), 0.69 (s, 3H). LCMS Rt=0.904min(1.5分間のクロマトグラフィー)、C24H37N3O2[M+H−H2O]+のESI計算値382、実測値382.
化合物208:1H NMR (CDCl3, 400MHz): δ7.78 (s, 1H), 7.66 (s, 1H), 5.32 - 5.24 (m, 1H), 5.18 - 5.10 (m, 1H), 2.70 - 2.60 (m, 1H), 2.28 - 1.03 (m, 32H), 0.96 (s, 3H), 0.66 (s, 3H). LCMS Rt=0.864min(1.5分間のクロマトグラフィー)、C24H37N3O2[M+H]+のMS ESI計算値400、実測値400.
化合物209:1H NMR (CDCl3, 400MHz): δ8.10 (s, 1H), 5.33 - 5.23 (m, 2H), 4.42 (q, J = 7.0 Hz, 2H), 3.47 (br. s., 1H), 2.62 - 2.52 (m, 1H), 2.25 - 1.00 (m, 31H), 0.95 (s, 3H), 0.68 (s, 3H). LCMS Rt=1.342min(2分間のクロマトグラフィー)、10−80AB、C27H41N3O4[M+Na]+のMS ESI計算値494、実測値494.
化合物210:1H NMR (CDCl3, 400MHz): δ8.17 (s, 1H), 5.32 - 5.12 (m, 2H), 4.44 (q, J = 7.0 Hz, 2H), 2.69 - 2.60 (m, 1H), 2.29 - 1.02 (m, 33H), 0.96 (s, 3H), 0.66 (s, 3H)LCMS Rt=1.278min(2分間のクロマトグラフィー)、C27H41N3O4[M+H−H2O]+のMS ESI計算値454、実測値454.
化合物212:1H NMR (DMSO-d6, 400MHz): δ8.58 (s, 1H), 5.60 - 5.53 (m, 1H), 5.41 - 5.34 (m, 1H), 4.27 (brs., 1H), 2.84 - 2.74 (m, 1H), 2.20-1.00 (m, 26H), 0.92 (s, 3H), 0.59 (s, 3H). LCMS Rt=0.837min(1.5分間のクロマトグラフィー)、C25H37N3O4[M+H−H2O]+のMS ESI計算値425、実測値425.
化合物214:1H NMR (CDCl3, 400MHz): δ8.13 (s, 1h), 6.58 (br. s., 1H), 5.51 (br. s., 1H), 5.31 - 5.17 (m, 2H), 2.64 - 2.56 (m, 1H), 2.30 - 1.03 (m, 26H), 0.96 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.189min(2分間のクロマトグラフィー)、C25H38N4O3[M+Na]+のMS ESI計算値465、実測値465.
化合物216:1H NMR (CDCl3, 400MHz): δ8.02 (s, 1H), 5.34-5.24 (m, 2H), 2.66-2.60 (m, 1H), 2.32-1.07 (m, 25H), 0.98 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.532min(2分間のクロマトグラフィー)、C25H36N4O2[M+H−H2O]+のMS ESI計算値407、実測値407.
化合物217:1H NMR (CDCl3, 400MHz): δ7.66 (s, 1H), 5.23-5.14 (m, 2H), 4.80 (s, 2H), 2.62-2.53 (m, 1H), 2.26-1.01 (m, 27H), 0.96 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.165min(2分間のクロマトグラフィー)、C25H39N3O3[M+Na]+のMS ESI計算値452、実測値452.
化合物218:1H NMR (CDCl3, 400MHz): δ7.62 (s, 1H), 5.30-5.05 (m, 2H), 4.84 (s, 2H), 2.64-2.62 (m, 1H), 2.33-1.00 (m, 27H), 0.95 (s, 3H), 0.65 (s, 3H). LCMS Rt=1.138min(2分間のクロマトグラフィー)、C25H39N3O3[M+H]+のMS ESI計算値430、実測値430.
化合物219:1H NMR (CDCl3, 400MHz): δ8.93 (s, 1H), 7.97 (s, 1H), 7.07 (s, 1H), 5.38 - 5.12 (m, 2H), 2.67 (t, J = 8.8 Hz, 1H), 2.30 - 2.07 (m, 2H), 1.83 - 1.64 (m, 4H), 1.62 - 1.10 (m, 35H), 1.05 - 0.90 (m, 1H), 0.89 - 0.79 (m, 1H), 0.77 (s, 3H), 0.70 (s, 3H). LCMS Rt=2.135min(4分間のクロマトグラフィー)、30−90AB、C28H38FN3O2[M+H]+のMS ESI計算値468、実測値468.19F NMR(CDCl3,400MHz):δ−85.326.
化合物220:1H NMR (CDCl3, 400MHz): δ8.35 (s, 1H), 8.07 (s, 1H), 7.19 (s, 1H), 5.29 - 5.15 (m, 2H), 2.68 (t, J=8.8 Hz, 1H), 2.26 - 2.08 (m, 2H), 1.81 - 1.64 (m, 4H), 1.63 - 1.12 (m, 21H), 0.97 (dq, J=5.5, 12.0 Hz, 1H), 0.89 - 0.79 (m, 1H), 0.77 (s, 3H), 0.70 (s, 3H). LCMS Rt=2.631min(4分間のクロマトグラフィー)、C28H38FN3O2[M+H]+のMS ESI計算値468、実測値468.19F NMR(CDCl3,400MHz):δ−84.137.
化合物221:1H NMR (CDCl3, 400MHz): δ8.95 (s, 1H), 7.99 (s, 1H), 7.11-7.07 (m, 1H), 5.38 - 5.19 (m, 2H), 3.41 (s, 3H), 3.21 (s, 2H), 2.70 (t, J = 8.8 Hz, 1H), 2.30 - 2.11 (m, 2H), 2.08 - 2.01 (m, 1H), 1.85 - 1.68 (m, 4H), 1.56 - 1.14 (m, 14H), 1.08 - 0.84 (m, 2H), 0.79 (s, 3H), 0.73 (s, 3H). LCMS Rt=0.928min(1.5分間のクロマトグラフィー)、C29H40FN3O3[M+H]+のMS ESI計算値498、実測値498.
化合物222:1H NMR (CDCl3, 400MHz): δ8.37 (s, 1H), 8.09 (s, 1H), 7.21 (d, J = 1.0 Hz, 1H), 5.33 - 5.17 (m, 2H), 3.41 (s, 3H), 3.21 (s, 2H), 2.70 (t, J = 8.9 Hz, 1H), 2.28 - 1.99 (m, 3H), 1.83 - 1.65 (m, 4H), 1.59 - 1.15 (m, 14H), 1.08 - 0.83 (m, 2H), 0.79 (s, 3H), 0.73 (s, 3H). LCMS Rt=0.950min(1.5分間のクロマトグラフィー)、C29H40FN3O3[M+H]+のMS ESI計算値498、実測値498.
化合物224:1H NMR (CDCl3, 400MHz): δ8.10 (s, 1H), 7.01 (br. s., 1H), 5.28 - 5.15 (m, 2H), 3.65 - 3.61 (m, 2H), 3.57 - 3.51 (m, 2H), 3.38 (s, 3H), 2.63 - 2.55 (m, 1H), 2.27 - 0.99 (m, 26H), 0.96 (s, 3H), 0.70 (s, 3H). LCMS Rt=0.891min(1.5分間のクロマトグラフィー)、C28H44N4O4[M+Na]+のMS ESI計算値523、実測値523.
化合物225:1H NMR (CDCl3, 400MHz): δ8.12 (s, 1H), 5.30-5.15 (m, 2H), 4.06 - 3.56 (m, 4H), 2.65-2.50 (m, 1H), 2.25 - 1.01 (m, 30H), 0.95 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.263min(2分間のクロマトグラフィー)、C29H44N4O3[M+Na]+のMS ESI計算値519、実測値519.
化合物226:1H NMR (CDCl3, 400MHz): δ7.64 (s, 1H), 5.25 - 5.11 (m, 2H), 4.76 (s, 2H), 2.58 (t, J = 8.9 Hz, 1H), 2.24 - 2.13 (m, 1H), 2.10-2.00 (m, 1H), 1.79 - 1.10 (m, 23H), 1.05-0.90 (m, 1H), 0.85 - 0.78 (m, 1H), 0.75 (s, 3H), 0.68 (s, 3H). LCMS Rt=1.211min(2.0分間のクロマトグラフィー)、C25H39N3O3[M+H]+のMS ESI計算値430、実測値430.
化合物227:1H NMR (CDCl3, 400MHz): δ7.63 (s, 1H), 5.31 - 5.04 (m, 2H), 4.84 (s, 2H), 2.70-2.55 (m, 1H), 2.25-2.15 (m, 1H), 2.10-2.00 (m, 1H), 1.88 - 1.13 (m, 30H), 1.04 - 0.90 (m, 1H), 0.89 - 0.78 (m, 1H), 0.76 (s, 3H), 0.66 (s, 3H). LCMS Rt=1.167min(2.0分間のクロマトグラフィー)、C25H39N3O3[M+H]+のMS ESI計算値430、実測値430.
化合物225:1H NMR (DMSO-d6, 400MHz): δ8.40-8.35 (m, 1H), 8.15 (s, 1H), 5.66 - 5.34 (m, 2H), 4.27 (s, 1H), 2.81 - 2.70 (m, 4H), 2.10 - 1.99 (m, 2H), 1.93 - 1.58 (m, 5H), 1.54 - 1.31 (m, 7H), 1.29 - 1.08 (m, 10H), 1.08 - 0.95 (m, 2H), 0.92 (s, 3H), 0.60 (s, 3H). LCMS Rt=0.922min(1.5分間のクロマトグラフィー)、C26H40N4O3[M+Na]+のMS ESI計算値479、実測値479.
化合物229:1H NMR (DMSO-d6, 400MHz): δ8.50 - 8.40 (m, 1H), 8.14 (s, 1H), 5.62-5.36 (m, 2H), 3.22 - 3.22 (m, 1H), 3.28 - 3.22 (m, 2H), 2.77-2.73 (m, 1H), 2.05-2.02 (m, 2H), 1.91 - 1.78 (m, 2H), 1.71 - 1.69 (m, 1H), 1.69 - 1.61 (m, 2H), 1.51 - 1.32 (m, 7H), 1.26 - 0.98 (m, 15H), 0.91 (s, 3H), 0.59 (s, 3H). LCMS Rt=1.123min(1.5分間のクロマトグラフィー)、C27H42N4O3[M+Na]+のMS ESI計算値493、実測値493.
化合物230:1H NMR (DMSO-d6, 400MHz): δ8.43 (t, J = 5.8 Hz, 1H), 8.15 (s, 1H), 5.64 - 5.35 (m, 2H), 3.23 - 3.14 (m, 2H), 2.80 - 2.71 (m, 1H), 2.10-2.00 (m, 2H), 1.91 - 1.61 (m, 5H), 1.57 - 1.31 (m, 10H), 1.26 - 0.95 (m, 11H), 0.91 (s, 3H), 0.86 (t, J = 7.4 Hz, 3H), 0.59 (s, 3H). LCMS Rt=1.186min(1.5分間のクロマトグラフィー)、C28H44N4O3[M+Na]+のMS ESI計算値507、実測値507.
化合物231:1H NMR (DMSO-d6, 400MHz): δ8.51 (d, J = 4.4 Hz, 1H), 8.15 (s, 1H), 5.59 (d, J = 18.1 Hz, 1H), 5.38 (d, J = 17.8 Hz, 1H), 4.28 (s, 1H), 2.82-2.80 (m, 1H), 2.75- 2.72 (m, 1H), 2.10 - 0.95 (m, 26H), 0.91 (s, 3H), 0.75 - 0.47 (m, 6H). LCMS Rt=1.337min(2分間のクロマトグラフィー)、C28H42N4O3[M+Na]+のMS ESI計算値505、実測値505.
化合物232:1H NMR (DMSO-d6, 400MHz): δ10.38 (s, 1H), 8.35 (s, 1H), 7.78 (d, J = 7.8 Hz, 2H), 7.36 (t, J = 8.0 Hz, 2H), 7.15 - 7.09 (m, 1H), 5.68 (d, J = 17.8 Hz, 1H), 5.47 (d, J = 18.1 Hz, 1H), 4.28 (s, 1H), 2.82 - 2.75 (m, 1H), 2.12 - 1.11 (m, 25H), 0.92 (s, 3H), 0.62 (s, 3H). LCMS Rt=1.474min(2分間のクロマトグラフィー)、C31H42N4O3[M+Na]+のMS ESI計算値541、実測値541.
化合物233:1H NMR (CDCl3, 400MHz): δ6.90-6.85 (m, 1H), 6.81 (t, J = 6.8 Hz, 1H), 5.43-5.31 (m, 2H), 2.71 (t, J = 8.8 Hz, 1H), 2.25-2.12 (m, 2H), 1.77-1.53 (m, 4H), 1.38-1.21 (m, 18H), 1.17-0.85 (m, 2H), 0.77 (s, 3H), 0.71 (s, 3H). LCMS Rt=0.974min(1.5分間のクロマトグラフィー)、C28H37F2N3O2[M+H]+のMS ESI計算値486、実測値486.
化合物234:1H NMR (CDCl3, 400MHz): δ7.30 (d, J = 8 Hz, 1H), 6.93-6.89 (m, 1H), 5.56-5.46 (m, 2H), 2.66 (t, J = 8.4 Hz, 1H), 2.59-2.12 (m, 2H), 1.74-1.53 (m, 4H), 1.47-1.24 (m, 18H), 1.21-0.84 (m, 2H), 0.77 (s, 3H), 0.74 (s, 3H). LCMS Rt=1.011min(1.5分間のクロマトグラフィー)、C28H37F2N3O2[M+H]+のMS ESI計算値486、実測値468
化合物236:1H NMR (CDCl3, 400MHz): δ8.58 (d, J = 1.2 Hz, 1H), 8.43 (d, J = 1.6 Hz, 1H), 8.33 (s, 1H) 5.37-5.24 (m, 2H), 2.70 (t, J = 8 Hz, 1H), 2.24-2.11 (m, 2H), 1.72-1.55 (m, 7H), 1.50-1.20 (m, 16H), 0.99-0.83 (m, 3H), 0.77 (s, 3H), 0.71 (s, 3H). LCMS Rt=1.336min(2分間のクロマトグラフィー)、C27H38N4O2[M+H]+のMS ESI計算値451、実測値451.
化合物237:1H NMR (CDCl3, 400MHz): δ7.93 (s, 1H), 7.65-7.61 (m, 1H), 7.28 (s, 1H), 6.91-6.87 (m, 1H), 5.22-5.10 (m, 2H), 2.64 (t, J = 8.4 Hz, 1H), 2.12-2.02 (m, 2H), 1.73-1.54 (m, 7H), 1.37-1.20 (m, 16H), 0.81-0.78 (m, 3H), 0.76 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.389min(2分間のクロマトグラフィー)、C29H39FN2O2[M+H]+のMS ESI計算値467、実測値467.
化合物238:1H NMR (CDCl3, 400MHz): δ8.00 (s, 1H), 7.69-7.66 (m, 1H), 6.95-6.91 (m, 1H), 6.84 (d, J = 8.8 Hz,, 1H), 5.13-5.03 (m, 2H), 2.64 (t, J = 9.2 Hz, 1H), 2.12-2.09 (m, 2H), 1.71-1.52 (m, 8H), 1.37-1.22 (m, 16H), 1.20-0.82 (m, 3H), 0.76 (s, 3H), 0.70 (s, 3H).
LCMS Rt=1.436min(2分間のクロマトグラフィー)、C29H39FN2O2[M+H]+のMS ESI計算値467、実測値467.
化合物239:1H NMR (CDCl3, 400MHz): δ7.99 (s, 1H), 7.36 (d, J = 8.4 Hz,, 1H), 7.15 (d, J = 6 Hz,, 2H), 5.18-5.08 (m, 2H), 2.64 (d, J = 8.8 Hz, 1H), 2.19-2.09 (m, 2H), 1.72-1.52 (m, 8H), 1.37-1.21 (m, 16H), 1.18-0.82 (m, 3H), 0.76 (s, 3H), 0.70 (s, 3H). LCMS Rt=0.963min(1.5分間のクロマトグラフィー)、C29H39FN2O2[M+H]+のMS ESI計算値467、実測値467.
化合物240:1H NMR (CDCl3, 400MHz): δ7.89 (s, 1H), 7.66 (t, J = 8.4 Hz,, 1H), 7.24 (t, J = 2 Hz,, 1H), 7.08 (d, J = 2.4 Hz,, 1H), 5.24-5.12 (m, 2H), 2.64 (t, J = 8.4 Hz, 1H), 2.12-2.17 (m, 2H), 1.73-1.51 (m, 4H), 1.47-1.23 (m, 18H), 1.20-0.82 (m, 3H), 0.76 (s, 3H), 0.70 (s, 3H). LCMS Rt=0.986min(1.5分間のクロマトグラフィー)、C29H39FN2O2[M+H]+のMS ESI計算値467、実測値467.
化合物242:1H NMR (CDCl3, 400MHz): δ8.63 (s, 1H), 8.55 (s,1H), 8.26 (s, 1H) 5.37-5.20 (m, 2H), 2.69 (t, J = 8.4 Hz, 1H), 2.26-2.17 (m, 2H), 1.75-1.52 (m, 7H), 1.37-1.20 (m, 16H), 0.86-0.83 (m, 3H), 0.77 (s, 3H), 0.74 (s, 3H). LCMS Rt=1.257min(2分間のクロマトグラフィー)、C27H38N4O2[M+H]+のMS ESI計算値451、実測値451.
化合物244:1H NMR (CDCl3, 400MHz): δ7.69 (d, J = 7.6 Hz, 1H), 7.31 -7.27 (m,, 2H), 5.46-5.35 (m, 2H), 2.71 (t, J = 8.8 Hz, 1H), 2.14-2.15 (m, 2H), 1.75-1.52 (m, 8H), 1.41-1.24(m, 15H), 1.21-0.84(m, 2H), 0.77 (s, 3H), 0.71 (s, 3H). LCMS Rt=1.373min(2分間のクロマトグラフィー)、C28H38FN3O2[M+H]+のMS ESI計算値468、実測値468.
化合物245:1H NMR (CDCl3, 400MHz): δ8.05-8.01 (m, 1H), 7.17 -7.12 (m,, 1H), 6.97 (t, J = 8.8 Hz, 1H), 5.43-5.31 (m, 2H), 2.71 (t, J = 8.8 Hz, 1H), 2.12-2.11 (m, 2H), 1.76-1.52 (m, 6H), 1.41-1.25 (m, 16H), 1.21-0.84(m, 2H), 0.77 (s, 3H), 0.72 (s, 3H). LCMS Rt=1.392min(2分間のクロマトグラフィー)、C28H38FN3O2[M+H]+のMS ESI計算値468、実測値468.
化合物246:1H NMR (CDCl3, 400MHz): δ7.87-7.84 (m, 1H), 7.47 -7.44 (m, 1H), 7.20 (t, J = 2 Hz, 1H), 5.54-5.44 (m, 2H), 2.65 (t, J = 8.8 Hz, 1H), 2.18-2.12 (m, 2H), 1.73-1.52 (m, 6H), 1.46-1.24 (m, 16H), 1.20-0.82 (m, 2H), 0.77 (s, 3H), 0.73 (s, 3H). LCMS Rt=0.999min(1.5分間のクロマトグラフィー)、C28H38FN3O2[M+H]+のMS ESI計算値468、実測値468.
化合物247:1H NMR (CDCl3, 400MHz): δ 7.88 (s, 1H), 7.40 (d, J = 9.2 Hz, 1H), 7.23 (d, J = 8.8 Hz, 1H), 5.43-5.30 (m, 2H), 2.69 (t, J = 9.2 Hz, 1H), 2.21 (s, 3H), 2.19-2.15 (m, 2H), 1.74-1.51 (m, 5H), 1.41-1.21 (m, 17H), 0.85-0.83 (m, 4H), 0.77 (s, 3H), 0.71 (s, 3H). LCMS Rt=1.002min(1.5分間のクロマトグラフィー)、C29H41N3O2S[M+H]+のMS ESI計算値496、実測値496.
化合物248:1H NMR (CDCl3, 400MHz): δ7.93 (t, J = 8.4 Hz, 1H), 7.26 (d, J = 3.6 Hz, 1H), 7.05 (m, 1H), 5.40-5.30 (m, 2H), 2.70 (t, J = 8.4 Hz, 1H), 2.53 (s, 3H), 2.17-2.13 (m, 2H), 1.78-1.52 (m, 6H), 1.41-1.21 (m, 16H), 0.85-0.83 (m, 3H), 0.77 (s, 3H), 0.72 (s, 3H). LCMS Rt=0.970min(1.5分間のクロマトグラフィー)、C29H41N3O2S[M+H]+のMS ESI計算値496、実測値496.
化合物249:1H NMR (CDCl3, 400MHz): δ7.74 (d, J = 8.8 Hz, 1H), 7.55 (s, 1H), 7.28 (s, 1H), 5.51-5.41 (m, 2H), 2.63 (t, J = 8.4 Hz, 1H), 2.55 (s, 3H), 2.52-2.11 (m, 2H), 1.74-1.51 (m, 5H), 1.40-1.23 (m, 17H), 1.20-0.81 (m, 3H), 0.76 (s, 3H), 0.73 (s, 3H). LCMS Rt=0.959min(1.5分間のクロマトグラフィー)、C29H41N3O2S[M+H]+のMS ESI計算値496、実測値496.
化合物250:1H NMR (CDCl3, 400MHz): δ7.92 (s, 1H),7.68 (s, 1H), 7.60 (d, J = 8.84 Hz, 1H), 7.04-7.02 (m, 1H), 5.24-5.11 (m, 2H), 2.64 (t, J = 8.8 Hz, 1H), 2.20-2.12 (m, 2H), 1.76-1.51 (m, 4H), 1.28-1.21 (m, 20H), 1.18-0.82 (m, 3H), 0.76 (s, 3H), 0.74 (s, 3H). LCMS Rt=0.993min(2分間のクロマトグラフィー)、C29H39ClN2O2[M+H]+のMS ESI計算値483、実測値483.
化合物251:1H NMR (CDCl3, 400MHz): δ8.00 (s, 1H),7.65 (d, J = 8.4 Hz, 1H), 7.20 (s, 1H), 7.13 (d, J = 8.4 Hz, 1H), 5.15-5.04 (m, 2H), 2.64 (t, J = 8.8 Hz, 1H), 2.20-2.11 (m, 2H), 1.72-1.53 (m, 4H), 1.38-1.21 (m, 22H), 1.18-0.83 (m, 3H), 0.77 (s, 3H), 0.71 (s, 3H)
LCMS Rt=1.019min(2分間のクロマトグラフィー)、C29H39ClN2O2[M+H]+のMS ESI計算値483、実測値483.
化合物252:1H NMR (CDCl3, 400MHz): δ7.88 (s, 1H), 7.62 (d, J = 9.6 Hz, 2H), 7.22-7.19 (m, 1H), 5.30-5.12 (m, 2H), 2.64 (d, J = 8 Hz, 1H), 2.20-2.09 (m, 2H), 1.73-1.51 (m, 4H), 1.37-1.21 (m, 19H), 1.18-0.98 (m, 3H), 0.76 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.016min(1.5分間のクロマトグラフィー)、C29H39ClN2O2[M+H]+のMS ESI計算値483、実測値483.
化合物253:1H NMR (CDCl3, 400MHz): δ7.98 (s, 1H), 7.71 (s, 1H), 7.33-7.31 (m, 1H), 7.13 (d, J = 9.2 Hz, 1H), 5.17-5.07 (m, 2H), 2.64 (d, J = 8.8 Hz, 1H), 2.19-2.09 (m, 2H), 1.72-1.55 (m, 4H), 1.37-1.21 (m, 21H), 1.18-0.82 (m, 3H), 0.76 (s, 3H), 0.70 (s, 3H). LCMS Rt=1.013min(1.5分間のクロマトグラフィー)、C29H39ClN2O2[M+H]+のMS ESI計算値483、実測値483.
化合物255:1H NMR (CDCl3, 400MHz): δ 7.11 (d, J=8.3 Hz, 2H), 6.88 (d, J=8.5 Hz, 2H), 3.82 (s, 3H), 3.69 - 3.56 (m, 2H), 2.66 (t, J=8.8 Hz, 1H), 2.22 - 1.72 (m, 5H), 1.65 (d, J=7.8 Hz, 3H), 1.59 - 1.58 (m, 1H), 1.53 - 1.40 (m, 8H), 1.35 - 1.04 (m, 11H), 0.97 (s, 3H), 0.65 (s, 3H).
LCMS Rt=1.224min(2分間のクロマトグラフィー)、C29H42O3[M−18+H]+のMS ESI計算値421、実測値421.
化合物256:1H NMR (CDCl3, 400MHz): δ 7.38 - 7.31 (m, 2H), 7.28 - 7.24 (m, 1H), 7.22 - 7.16 (m, 2H), 3.76 - 3.63 (m, 2H), 2.67 (t, J=8.9 Hz, 1H), 2.25 - 2.02 (m, 2H), 1.97 (t, J=13.2 Hz, 1H), 1.92 - 1.72 (m, 2H), 1.71 - 1.58 (m, 3H), 1.55 - 1.39 (m, 9H), 1.36 - 1.26 (m, 5H), 1.25 - 1.18 (m, 3H), 1.16 - 1.02 (m, 2H), 0.97 (s, 3H), 0.67 (s, 3H). LCMS Rt=1.240min(2分間のクロマトグラフィー)、C28H40O2[M−18+H]+のMS ESI計算値391、実測値391.
化合物258:1H NMR (CDCl3, 400MHz): δ 7.25 - 7.00 (m, 4H), 3.78 - 3.64 (m, 2H), 2.71 - 2.60 (m, 1H), 2.24 - 2.05 (m, 2H), 1.74 - 1.11 (m, 22H), 1.01 - 0.89 (m, 1H), 0.76 (s, 4H), 0.66 (s, 3H). LCMS 1.484min(2分間のクロマトグラフィー)、C28F40FO2[M+H]+のMS ESI計算値427、実測値409[M−18]+.
化合物259:1H NMR (CDCl3, 400MHz): δ7.01 (s, 1H), 6.38 (dd, J=8.2, 1.5 Hz, 1H), 4.55-4.66 (m, 2H), 2.57 (t, J=8.8 Hz, 1H), 2.14-2.26 (m, 1H), 1.85-2.00 (m, 3H), 1.75 (t, J=7.4 Hz, 3H), 1.41-1.55 (m, 9H), 1.22-1.29 (m, 8H), 1.03-1.19 (m, 2H), 0.96 (s, 3H), 0.65 (s, 3H). LCMS Rt=2.747min(4.0分間のクロマトグラフィー)、C25H37FN2O2[M+H]+のMS ESI計算値417.28、実測値417.0([M+H]+.
1H NMR (260): (400 MHz, CDCl3) δ 8.04-8.03 (m, 1H), 5.27-5.17 (m, 2H), 3.65-3.48 (m, 2H), 3.29 - 3.09 (m, 3H), 2.59-2.57 (m, 1H), 2.21-2.20 (m, 1H), 2.06-2.05 (m, 3H), 1.95-1.67 (m, 2H), 1.66-1.60 (m, 5H), 1.57-1.45 (m, 8H), 1.42-1.27 (m, 9H), 1.23-1.05 (m, 2H), 0.96-0.87 (m, 4H), 0.85-0.83 (m, 2H), 0.69 (s, 3H). LCMS tR=1.238min(2分間のクロマトグラフィー)、30−90AB、C29H46N4O3[M+Na]+のMS ESI計算値521、実測値521.
1H NMR (261): (400 MHz, CDCl3) δ 8.03-7.98 (m, 1H), 5.27-5.21 (m, 2H), 4.98-4.68 (m, 1H), 3.11 - 2.95 (m, 3H), 2.61-2.59 (m, 1H), 2.19-2.15 (m, 1H), 2.07-2.05 (m, 1H), 1.96-1.76 (m, 2H), 1.73-1.70 (m, 3H), 1.52-1.47 (m, 9H), 1.43-1.07 (m, 16H), 0.96 (s, 3H), 0.69 (s, 3H). LCMS Rt=1.213min(2分間のクロマトグラフィー)、30−90AB、C29H46N4O3 [M+Na]+のMS ESI計算値521、実測値521.
1H NMR (262): (400MHz, DMSO-d6) δ 8.15 (s, 1H), 7.51 (s, 1H), 5.63 - 5.36 (m, 2H), 4.26 (s, 1H), 2.78 - 2.73 (m, 1H), 2.14 - 1.00 (m, 34H), 0.92 (s, 3H), 0.60 (m, 3H). LCMS tR=1.472min(2分間のクロマトグラフィー)、10−80AB、C29H46N4O3[M−H2O+H]+のMS ESI計算値481、実測値481.
1H NMR (263): (400MHz, CDCl3) δ 8.09 (s, 1H), 5.26 - 5.15 (m, 2H), 4.55 - 4.50 (m, 2H), 4.23 - 4.19 (m, 2H), 2.57 - 2.37 (m, 1H), 2.36 - 1.06 (m, 28H), 0.95 (s, 3H), 0.68 (m, 3H). LCMS tR=1.333min(2分間のクロマトグラフィー)、10−80AB、C28H42N4O3[M−H2O+H]+のMS ESI計算値453、実測値453.
本明細書中に提供される化合物は、様々なアッセイを用いて評価され得る;それらのアッセイの例を下記に記載する。
TBPS結合のステロイド阻害
細胞電気生理学を使用して、異質細胞系において、本発明者らのGABAAレセプター調節因子の薬理学的特性を測定する。各化合物を、最大下アゴニスト用量(GABA EC20=2μM)でGABAによって媒介される電流に影響する能力について試験する。LTK細胞を、GABAレセプターのα1β2γ2サブユニットで安定にトランスフェクトし、そしてCHO細胞を、リポフェクタミン法によって、α4β3δサブユニットで一過性トランスフェクションする。細胞を約50%〜80%のコンフルエンスで継代し、次いで、抗生物質も抗真菌物質も含まない2mlの培養完全培地を含む35mmの滅菌培養ディッシュに播種した。細胞のコンフルエントなクラスターを電気的に交接させる(Pritchettら, Science, 1988, 242, 1306−1308)。遠くの細胞の応答は充分に電圧クランプされないこと、および交接の程度に関する不確実性(Verdoornら, Neuron 1990, 4, 919−928)に起因して、細胞を、1個の細胞の記録を可能にする密度で(他の細胞との目に見える連結がないように)培養した。
一実施形態において、例えば、以下の項目が提供される。
(項目1)
式(I):
の化合物またはその薬学的に受容可能な塩であって;式(I)において:
環Aは、カルボシクリル、ヘテロシクリル、アリール、またはヘテロアリールであり;
R 1 は、水素、C 1〜5 ハロアルキル(例えば、C 1〜3 ハロアルキル)、C 1〜5 アルキル(例えば、C 1〜3 アルキル)、C 2〜6 アルケニル、またはC 3〜6 カルボシクリルであり;
R 2a およびR 2b の各々は独立して、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、または−OR A2 であり、ここでR A2 は、水素またはC 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり;
R 3a は、水素または−OR A3 であり、ここでR A3 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 3b は、水素であるか;あるいはR 3a とR 3b とは一緒になって、オキソ(=O)基を形成し;
R 4a は、水素、C 1〜6 アルキル、または−OR A4 であり、ここでR A4 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 4b は、水素またはC 1〜6 アルキルであるか;あるいはR 4a とR 4b とは一緒になって、オキソ(=O)基を形成するか;あるいはR 4a とR 4b とはそれらが結合している炭素原子と一緒になって、環(例えば、3〜6員環(例えば、カルボシクリルまたはヘテロシクリル環))を形成し;
R 5 は存在しないか、または水素であり;
R 7a およびR 7b の各々は独立して、水素またはハロゲンであり;
は、単結合または二重結合を表し、ここで
の一方が二重結合である場合、他方の
は単結合であり;そして
の一方が二重結合である場合、R 5 は存在しない、化合物またはその薬学的に受容可能な塩。
(項目2)
前記化合物は、式(I−a):
の化合物であり、
式(I−a)において:
R 6 は、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、C 1〜6 ハロアルキル、ハロゲン、シアノ、ニトロ、OR A6 、C(=O)R A6 、C(=O)OR A6 、SR B6 、S(=O)R B6 、S(=O) 2 R B6 、N(R C6 )(R D6 )、C(=O)N(R C6 )(R D6 )、N(R C6 )C(=O)R A6 であり;そして
nは、0、1、2、または3であり;
ここでR A6 は、水素またはC 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、またはC 1〜6 ハロアルキルであり;R B6 は、C 1〜6 アルキルまたはC 3〜6 カルボシクリルであり;そしてR C6 およびR D6 の各々は独立して、水素、C 1〜6 アルキル、カルボシクリル、ヘテロシクリル、アリール、またはヘテロアリールであるか、あるいはR C6 およびR D6 はそれらが結合している窒素原子と一緒になって、環(例えば、3〜6員環(例えば、カルボシクリルまたはヘテロシクリル環))を形成する、項目1に記載の化合物またはその薬学的に受容可能な塩。
(項目3)
Aは、炭素結合(例えば、Aが炭素原子を介して連結している)5もしくは6員ヘテロアリール、または6員アリールである、前出の項目のいずれか1項に記載の化合物。
(項目4)
Aは、
であり、
ここで:
Xは、−O−、−S−、または−N(R N )−であり、ここでR N は独立して、水素、C 1〜6 アルキル、−C(=O)R GA 、−C(=O)OR GA 、−C(=O)N(R GA ) 2 、−S(=O) 2 R GA 、−S(=O) 2 OR GA 、−S(=O) 2 N(R GA ) 2 、または窒素保護基であり;
R 6a 、R 6b 、R 6c 、R 6d 、およびR 6e の各例は独立して、水素、ハロゲン、−NO 2 、−CN、−OR GA 、−N(R GA ) 2 、−C(=O)R GA 、−C(=O)OR GA 、−OC(=O)R GA 、−OC(=O)OR GA 、−C(=O)N(R GA ) 2 、−N(R GA )C(=O)R GA 、−OC(=O)N(R GA ) 2 、−N(R GA )C(=O)OR GA 、−N(R GA )C(=O)N(R GA ) 2 、−S(=O) 2 R GA 、−S(=O) 2 OR GA 、−OS(=O) 2 R GA 、−S(=O) 2 N(R GA ) 2 、−N(R GA )S(=O) 2 R GA 、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、または3〜6員ヘテロシクリルであるか;あるいはR 6a 、R 6b 、R 6c 、R 6d 、およびR 6e のうちの2個はそれらが結合している原子と一緒になって、ヘテロシクリル、アリール、またはヘテロアリール環を形成し;そして
R GA の各例は独立して、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、3〜6員ヘテロシクリル、アリール、ヘテロアリール、酸素に結合している場合には酸素保護基、窒素に結合している場合には窒素保護基であるか、あるいは2個のR GA 基は、介在する原子と一緒になって、ヘテロシクリルまたはヘテロアリール環を形成する、項目3に記載の化合物。
(項目5)
R 6a 、R 6b 、R 6c 、R 6d 、およびR 6e のうちの少なくとも1個は、水素である、項目4に記載の化合物。
(項目6)
R 6a 、R 6b 、R 6c 、R 6d 、およびR 6e のうちの少なくとも1個は、C 1〜2 アルキル、−CO 2 R GA 、−C(=O)R GA 、−CN、−NO 2 、またはハロゲンであり、ここでR GA は、C 1〜2 アルキルである、項目4に記載の化合物。
(項目7)
R 6a 、R 6b 、R 6c 、R 6d 、およびR 6e のうちの少なくとも1個は、−CH 3 である、項目5に記載の化合物。
(項目8)
R 6a 、R 6b 、R 6c 、R 6d 、およびR 6e は、水素である、項目4に記載の化合物。
(項目9)
Aは、少なくとも1個の窒素原子を含む環である、項目4に記載の化合物。
(項目10)
前記化合物は、式(II−b):
の化合物であり、式(II−b)において:
環Eは、ヘテロシクリルまたはヘテロアリールである、前出の項目のいずれか1項に記載の化合物。
(項目11)
Eは、少なくとも1個の窒素原子を含む環である、項目10に記載の化合物。
(項目12)
Eは、
から選択される、項目11に記載の化合物。
(項目13)
Aは、
である、前出の項目のいずれか1項に記載の化合物。
(項目14)
Eは、少なくとも2個の窒素原子を含む環である、項目10〜12のいずれか1項に記載の化合物。
(項目15)
Eは、少なくとも2個の窒素原子を含む環であり、そしてR 2 、R 3a 、R 4a またはR 4b のうちの少なくとも1個は、水素ではない、項目14に記載の化合物。
(項目16)
Eは、少なくとも3個の窒素原子を含む環である、項目10〜15のいずれか1項に記載の化合物。
(項目17)
Eは、4個の窒素原子を含む環である、項目10〜16のいずれか1項に記載の化合物。
(項目18)
R 2 、R 3a 、R 4a またはR 4b のうちの少なくとも1個は、水素ではない、項目17に記載の化合物。
(項目19)
Eは、2個、3個または4個の窒素原子を含む環である、項目10〜18のいずれか1項に記載の化合物。
(項目20)
Eは、ピラゾール、トリアゾール、テトラゾール、インダゾール、ベンゾトリアゾール、トリアゾロピリジン、トリアゾロピラジン、ピラゾロピラジン、またはモルホリンから選択される環である、項目10〜19のいずれか1項に記載の化合物。
(項目21)
Aは、6員ヘテロシクリル環(例えば、少なくとも2個のヘテロ原子を含む6員ヘテロシクリル環)である、項目1〜2のいずれか1項に記載の化合物。
(項目22)
Aは、5〜6員ヘテロシクリル環であり、そしてnは、1または2である、項目1〜2のいずれか1項に記載の化合物。
(項目23)
Eは、モルホリンであり、そしてnは、1または2である、項目10に記載の化合物。
(項目24)
Aは、アリール環である、前出の項目のいずれか1項に記載の化合物。
(項目25)
Aは、フェニルであり、そしてnは、1または2である、前出の項目のいずれか1項に記載の化合物。
(項目26)
R 1 は、水素、置換のC 1〜3 アルキル、または非置換のC 1〜3 アルキルである、前出の項目のいずれか1項に記載の化合物。
(項目27)
R 1 は、水素、メチル、またはメトキシメチルである、前出の項目のいずれか1項に記載の化合物。
(項目28)
R 1 は、メチルである、項目27に記載の化合物。
(項目29)
R 2 は、水素、−OR A2 であり、ここでR A2 は、水素、または置換もしくは非置換のC 1〜6 アルキル(例えば、メチル、エチル)である、前出の項目のいずれか1項に記載の化合物。
(項目30)
R 3a は、−OR A3 であり、ここでR A3 は、水素、または置換もしくは非置換のC 1〜6 アルキル(例えば、メチル)である、前出の項目のいずれか1項に記載の化合物。
(項目31)
R 3a とR 3a とは一緒になって、オキソ(=O)基を形成する、項目1に記載の化合物。
(項目32)
R 4a は、水素、置換のC 1〜6 アルキル、または非置換のC 1〜6 アルキル(例えば、メチル)である、前出の項目のいずれか1項に記載の化合物。
(項目33)
R 4b は、水素、または置換のC 1〜6 アルキル、または非置換のC 1〜6 アルキル(例えば、メチル)である、前出の項目のいずれか1項に記載の化合物。
(項目34)
R 4a は、水素であり、そしてR 4b は、置換のC 1〜6 アルキルまたは非置換のC 1〜6 アルキル(例えば、メチル)である、項目1に記載の化合物。
(項目35)
R 4a およびR 4a の各々は独立して、非置換のC 1〜6 アルキル(例えば、メチル)である、前出の項目のいずれか1項に記載の化合物。
(項目36)
R 4a およびR 4a の各々は独立して、水素である、前出の項目のいずれか1項に記載の化合物。
(項目37)
R 5 は、水素である、前出の項目のいずれか1項に記載の化合物。
(項目38)
nは、0である、前出の項目のいずれか1項に記載の化合物。
(項目39)
nは、1であり、そしてR 6 は、置換もしくは非置換のC 1〜6 アルキル、C 1〜6 ハロアルキル、ハロゲン(例えば、−F、−Br、−Cl)、シアノ、−OR A6 、−C(=O)OR A6 、−SR B6 、−S(=O)R B6 、またはS(=O) 2 R B6 であり、ここでR A6 は、水素または置換もしくは非置換のC 1〜6 アルキル(例えば、メチル、エチル)、C 1〜6 ハロアルキル(例えば、−CF 3 )であり、そしてR B6 は、置換または非置換のC 1〜6 アルキルである、前出の項目のいずれか1項に記載の化合物。
(項目40)
nは、1であり、そしてR 6 は、ハロゲン(例えば、−F、−Br、−Cl)またはシアノである、前出の項目のいずれか1項に記載の化合物。
(項目41)
nは、1であり、そしてR 6 は、置換または非置換のC 1〜6 アルキル(例えば、メチル)である、前出の項目のいずれか1項に記載の化合物。
(項目42)
nは、1であり、そしてR 6 は、C 1〜6 ハロアルキル、−OR A6 、または−C(=O)OR A6 であり、ここでR A6 は、水素または置換もしくは非置換のC 1〜6 アルキル(例えば、メチル、エチル)、C 1〜6 ハロアルキル(例えば、−CF 3 )である、前出の項目のいずれか1項に記載の化合物。
(項目43)
nは、1であり、そしてR 6 は、SR B6 、−S(=O)R B6 、またはS(=O) 2 R B6 であり、ここでR B6 は、置換または非置換のC 1〜6 アルキル(例えば、メチル)である、前出の項目のいずれか1項に記載の化合物。
(項目44)
nは、2であり、そしてR 6 は独立して、置換もしくは非置換のC 1〜6 アルキル、C 1〜6 ハロアルキル、ハロゲン(例えば、−F、−Br、−Cl)、シアノ、−OR A6 、−C(=O)OR A6 、−SR B6 、−S(=O)R B6 、またはS(=O) 2 R B6 から選択され、ここでR A6 は、水素または置換もしくは非置換のC 1〜6 アルキル(例えば、メチル、エチル)、C 1〜6 ハロアルキル(例えば、−CF 3 )であり、そしてR B6 は、置換または非置換のC 1〜6 アルキルである、前出の項目のいずれか1項に記載の化合物。
(項目45)
nは、2であり、そしてR 6 は独立して、ハロゲン(例えば、−F、−Br、−Cl)から選択される、前出の項目のいずれか1項に記載の化合物。
(項目46)
nは、2であり、そしてR 6 のうちの1個は、フッ素である、前出の項目のいずれか1項に記載の化合物。
(項目47)
R 1 は、非置換のC 1〜3 アルキルであり、そしてR 2 、R 3a 、R 4a またはR 4b のうちの少なくとも1個は、水素ではない、前出の項目のいずれか1項に記載の化合物。
(項目48)
前記化合物は式(II−b)の化合物であり、そしてEは、少なくとも3個の窒素原子を含むヘテロアリール環である、項目10に記載の化合物。
(項目49)
前記化合物は、
である、項目1に記載の化合物。
(項目50)
前出の項目のいずれか1項に記載の化合物および薬学的に受容可能な賦形剤を含む、薬学的組成物。
(項目51)
被験体において鎮静および/または麻酔を誘導する方法であって、前記被験体に有効量の式(I):
の化合物またはその薬学的に受容可能な塩を投与する工程を含み;式(I)において:
環Aは、カルボシクリル、ヘテロシクリル、アリール、またはヘテロアリールであり;
R 1 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、またはC 3〜6 カルボシクリルであり;
R 2 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、または−OR A2 であり、ここでR A2 は、水素またはC 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり;
R 3a は、水素または−OR A3 であり、ここでR A3 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 3b は、水素であるか;あるいはR 3a とR 3b とは一緒になって、オキソ(=O)基を形成し;
R 4a は、水素、C 1〜6 アルキル、または−OR A4 であり、ここでR A4 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 4b は、水素またはC 1〜6 アルキルであり;R 4a とR 4b とは一緒になって、オキソ(=O)基を形成するか;あるいはR 4a とR 4b とはそれらが結合している炭素原子と一緒になって、環(例えば、3〜6員環(例えば、カルボシクリルまたはヘテロシクリル環))を形成し、
R 7a は、水素またはハロゲンであり;
R 7b は、水素であり;
R 5 は存在しないか、または水素であり;そして
は、単結合または二重結合を表し、ここで
の一方が二重結合である場合、他方の
は単結合であり;そして
の一方が二重結合である場合、R 5 は存在しない、
方法。
(項目52)
有効量の項目1に記載の化合物、その薬学的に受容可能な塩または化合物の薬学的組成物をそれを必要とする被験体に投与する方法であって、前記被験体は、投与2時間以内に鎮静および/または麻酔を経験する、方法。
(項目53)
前記被験体は、投与1時間以内に鎮静および/または麻酔を経験する、項目52に記載の方法。
(項目54)
前記被験体は、即時に鎮静および/または麻酔を経験する、項目52に記載の方法。
(項目55)
前記化合物は、静脈内投与によって投与される、項目52に記載の方法。
(項目56)
前記化合物は、慢性的に投与される、項目52に記載の方法。
(項目57)
前記被験体は、哺乳動物である、項目52に記載の方法。
(項目58)
前記被験体は、ヒトである、項目57に記載の方法。
(項目59)
前記化合物は、別の治療剤と組み合わせて投与される、項目52に記載の方法。
(項目60)
被験体において発作を処置するための方法であって、前記被験体に有効量の式(I):
の化合物またはその薬学的に受容可能な塩を投与する工程を含み;式(I)において:
環Aは、カルボシクリル、ヘテロシクリル、アリール、またはヘテロアリールであり;
R 1 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、またはC 3〜6 カルボシクリルであり;
R 2 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、または−OR A2 であり、ここでR A2 は、水素またはC 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり;
R 3a は、水素または−OR A3 であり、ここでR A3 は、水素、C 1〜6 アルキル、置換もしくは非置換のC 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 3b は、水素であるか;あるいはR 3a とR 3b とは一緒になって、オキソ(=O)基を形成し;
R 4a は、水素、C 1〜6 アルキル、または−OR A4 であり、ここでR A4 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 4b は、水素またはC 1〜6 アルキルであり;R 4a とR 4b とは一緒になって、オキソ(=O)基を形成するか;あるいはR 4a とR 4b とはそれらが結合している炭素原子と一緒になって、環(例えば、3〜6員環(例えば、カルボシクリルまたはヘテロシクリル環))を形成し、
R 7a は、水素またはハロゲンであり;
R 7b は、水素であり;
R 5 は存在しないか、または水素であり;そして
は、単結合または二重結合を表し、ここで
の一方が二重結合である場合、他方の
の一方が二重結合である場合、R 5 は存在しない、
方法。
(項目61)
被験体においててんかんまたは状態またはてんかん発作重積状態を処置するための方法であって、前記被験体に有効量の式(I):
の化合物またはその薬学的に受容可能な塩を投与する工程を含み;式(I)において:
環Aは、カルボシクリル、ヘテロシクリル、アリール、またはヘテロアリールであり;
R 1 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、またはC 3〜6 カルボシクリルであり;
R 2 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、または−OR A2 であり、ここでR A2 は、水素またはC 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり;
R 3a は、水素または−OR A3 であり、ここでR A3 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 3b は、水素であるか;あるいはR 3a とR 3b とは一緒になって、オキソ(=O)基を形成し;
R 4a は、水素、C 1〜6 アルキル、または−OR A4 であり、ここでR A4 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 4b は、水素またはC 1〜6 アルキルであり;R 4a とR 4b とは一緒になって、オキソ(=O)基を形成するか;あるいはR 4a とR 4b とはそれらが結合している炭素原子と一緒になって、環(例えば、3〜6員環(例えば、カルボシクリルまたはヘテロシクリル環))を形成し、
R 7a は、水素またはハロゲンであり;
R 7b は、水素であり;
R 5 は存在しないか、または水素であり;そして
は、単結合または二重結合を表し、ここで
の一方が二重結合である場合、他方の
は単結合であり;そして
の一方が二重結合である場合、R 5 は存在しない、
方法。
(項目62)
前記てんかん発作重積状態は、痙攣性てんかん発作重積状態(例えば、早期てんかん発作重積状態、確立したてんかん発作重積状態、難治性てんかん発作重積状態、超難治性てんかん発作重積状態)または非痙攣性てんかん発作重積状態(例えば、全般性てんかん発作重積状態、複雑性部分てんかん発作重積状態)である、項目61に記載の方法。
(項目63)
GABA機能に関連する障害の処置を必要とする被験体においてGABA機能に関連する障害を処置するための方法であって、前記被験体に治療有効量の式(I):
の化合物、その薬学的に受容可能な塩または化合物もしくはその薬学的に受容可能な塩のうちの1つの薬学的組成物を投与する工程を含み;式(I)において:
環Aは、カルボシクリル、ヘテロシクリル、アリール、またはヘテロアリールであり;
R 1 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、またはC 3〜6 カルボシクリルであり;
R 2 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、または−OR A2 であり、ここでR A2 は、水素またはC 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり;
R 3a は、水素または−OR A3 であり、ここでR A3 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 3b は、水素であるか;あるいはR 3a とR 3b とは一緒になって、オキソ(=O)基を形成し;
R 4a は、水素、C 1〜6 アルキル、または−OR A4 であり、ここでR A4 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 4b は、水素またはC 1〜6 アルキルであり;R 4a とR 4b とは一緒になって、オキソ(=O)基を形成するか;あるいはR 4a とR 4b とはそれらが結合している炭素原子と一緒になって、環(例えば、3〜6員環(例えば、カルボシクリルまたはヘテロシクリル環))を形成し、
R 7a は、水素またはハロゲンであり;
R 7b は、水素であり;
R 5 は存在しないか、または水素であり;そして
は、単結合または二重結合を表し、ここで
の一方が二重結合である場合、他方の
は単結合であり;そして
の一方が二重結合である場合、R 5 は存在しない、
方法。
(項目64)
CNS関連障害の処置を必要とする被験体においてCNS関連障害を処置するための方法であって、前記被験体に有効量の前出の項目のいずれかに記載の化合物またはその薬学的に受容可能な塩を投与する工程を含む、方法。
(項目65)
前記CNS関連障害は、睡眠障害、気分障害、統合失調症スペクトラム障害、痙攣障害、記憶および/または認知の障害、運動障害、人格障害、自閉症スペクトラム障害、疼痛、外傷性脳損傷、脈管疾患、物質乱用障害および/または離脱症候群、あるいは耳鳴である、項目64に記載の方法。
(項目66)
前記化合物は、経口投与される、項目64に記載の方法。
(項目67)
前記化合物は、筋肉内投与される、項目64に記載の方法。
(項目68)
前記被験体は、レット症候群、脆弱X症候群、またはアンジェルマン症候群を有する被験体である、項目64に記載の方法。
(項目69)
前記CNS関連障害は、睡眠障害、摂食障害、気分障害、統合失調症スペクトラム障害、痙攣障害、記憶および/または認知の障害、運動障害、人格障害、自閉症スペクトラム障害、疼痛、外傷性脳損傷、脈管疾患、物質乱用障害および/または離脱症候群、あるいは耳鳴である、項目64に記載の方法。
(項目70)
前記CNS関連障害は、うつ病(例えば、産後うつ)である、項目64に記載の方法。
(項目71)
前記CNS関連障害は、振顫(例えば、本態性振顫)である、項目64に記載の方法。
(項目72)
前記CNS関連障害は、摂食障害(例えば、神経性食欲不振症、神経性過食症、過食性障害、悪液質)である、項目64に記載の方法。
(項目73)
式(I):
の化合物またはその薬学的に受容可能な塩を含む固体組成物および滅菌希釈剤を含むキットであって;式(I)において:
環Aは、カルボシクリル、ヘテロシクリル、アリール、またはヘテロアリールであり;
R 1 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、またはC 3〜6 カルボシクリルであり;
R 2 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、C 3〜6 カルボシクリル、または−OR A2 であり、ここでR A2 は、水素またはC 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり;
R 3a は、水素または−OR A3 であり、ここでR A3 は、水素、C 1〜6 アルキル、C 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 3b は、水素であるか;あるいはR 3a とR 3b とは一緒になって、オキソ(=O)基を形成し;
R 4a は、水素、C 1〜6 アルキル、または−OR A4 であり、ここでR A4 は、水素、C 1〜6 アルキル、置換もしくは非置換のC 2〜6 アルケニル、C 2〜6 アルキニル、またはC 3〜6 カルボシクリルであり、そしてR 4b は、水素またはC 1〜6 アルキルであり;R 4a とR 4b とは一緒になって、オキソ(=O)基を形成するか;あるいはR 4a とR 4b とはそれらが結合している炭素原子と一緒になって、環(例えば、3〜6員環(例えば、カルボシクリルまたはヘテロシクリル環))を形成し、
R 7a は、水素またはハロゲンであり;
R 7b は、水素であり;
R 5 は存在しないか、または水素であり;そして
は、単結合または二重結合を表し、ここで
の一方が二重結合である場合、他方の
は単結合であり;そして
の一方が二重結合である場合、R 5 は存在しない、キット。
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