JP7060775B2 - New compound - Google Patents

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JP7060775B2
JP7060775B2 JP2018075114A JP2018075114A JP7060775B2 JP 7060775 B2 JP7060775 B2 JP 7060775B2 JP 2018075114 A JP2018075114 A JP 2018075114A JP 2018075114 A JP2018075114 A JP 2018075114A JP 7060775 B2 JP7060775 B2 JP 7060775B2
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hydroxyethanesulfonyl
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賢太郎 花田
修 小林
宏之 半沢
直樹 中尾
誠 鈴木
祥平 川崎
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DIRECTOR-GENERAL OF NATIONAL INSTITUTE OF INFECTIOUS DISEASES
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Description

本発明は、セラミド特異的輸送タンパク質(以後CERT(ceramide-transfer protein)と略することがある。)の機能を阻害可能とする新規化合物に関する。 The present invention relates to a novel compound capable of inhibiting the function of a ceramide-specific transport protein (hereinafter sometimes abbreviated as CERT (ceramide-transfer protein)).

小胞体で生合成された各種の膜脂質はそれぞれに異なるオルガネラへと移動しているが、その移動が起こる理由は長い間不明であった。小胞体で合成される脂質セラミドはゴルジ体へ輸送され、そこで主要膜リン脂質の一つであるスフィンゴミエリンへ変換されるが、近年、セラミドを小胞体からゴルジ体へ輸送する経路は、小胞輸送ではなく、専用の輸送タンパク質が働いていることが明らかにされた（非特許文献１）。 Various membrane lipids biosynthesized in the endoplasmic reticulum migrate to different organelles, but the reason for the migration has long been unknown. Lipid ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus, where it is converted to sphingomyelin, which is one of the major membrane phospholipids. It was clarified that a dedicated transport protein works instead of transport (Non-Patent Document 1).

即ち、セラミドは、細胞質に存在するCERTによって輸送されており、C末250残基のSTART(Steroidogenic acute regulator-related lipid transfer)ドメインがセラミドを脂質膜から特異的に引き抜き、膜間転移を行う。 That is, ceramide is transported by CERT present in the cytoplasm, and the START (Steroidogenic acute regulator-related lipid transfer) domain of C-terminal 250 residues specifically extracts ceramide from the lipid membrane and performs intermembrane transfer.

HPA-12((N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecamide)は、CERTの特異的阻害剤であるが（非特許文献２、３）、このHPA-12を利用した様々な研究報告例がある。例えばHPA-12でCERTを阻害するとC型肝炎ウイルスや偏性細胞内寄生細菌クラミジア属菌のヒト培養細胞での増殖が抑制されると報告されている（非特許文献４、５）。 HPA-12 ((N- (3-hydroxy-1-hydroxymethyl-3-phenylpropyl) dodecamide) is a specific inhibitor of CERT (Non-Patent Documents 2 and 3), but various HPA-12s are used. For example, it has been reported that inhibition of CERT with HPA-12 suppresses the growth of hepatitis C virus and the obligate intracellular parasite Chlamydia spp. In cultured human cells (non-patent literature). 4, 5).

Hanada,K.,Kumagai, K.,Yasuda, S.,Miura, Y.,Kawano, M.,Fukasawa, M.,and Nishijima,M. (2003) Molecular machinery for non-vesicular trafficking of ceramide.Nature 426,803-809Hanada, K., Kumagai, K., Yasuda, S., Miura, Y., Kawano, M., Fukasawa, M., and Nishijima, M. (2003) Molecular machinery for non-vesicular trafficking of ceramide. Nature 426,803 -809 Kumgai,et al.(2004)J.Biol.Chem.280,6488Kumgai, et al. (2004) J.Biol.Chem.280,6488 Yasuda,et al.(2001)J.Biol.Chem.276,43994Yasuda, et al. (2001) J.Biol.Chem.276,43994 H.Aizaki, K.Morikawa, M.Fukasawa, H.Hara, Y.Inoue, H.Tani, K.Saito, M.Nishijima, K.Hanada, Y.Matsuura, M.M.C. Lai, T.Miyamura, T.Wakita, T.Suzuki, J.Virol. 2008,82,5715.H.Aizaki, K.Morikawa, M.Fukasawa, H.Hara, Y.Inoue, H.Tani, K.Saito, M.Nishijima, K.Hanada, Y.Matsuura, M.M.C.Lai, T.Miyamura, T.Wakita , T.Suzuki, J.Virol. 2008,82,5715. C.A.Elwell, S.Jiang, J.H.Kim, A.Lee, T.Wittmann, K.Hanada, P.Melancon, J.N.Engel, PLoS Pathog. 2011,7,e1002198.C.A.Elwell, S.Jiang, J.H.Kim, A.Lee, T.Wittmann, K.Hanada, P.Melancon, J.N.Engel, PLoS Pathog. 2011,7, e1002198.

しかしHPA-12はセラミドと構造が似ているため、他の分子目標に対してoff target効果を与えてしまう虞がある。 However, since HPA-12 is similar in structure to ceramide, it may have an off target effect on other molecular targets.

本発明はかかる問題点に鑑みてなされたものであって、セラミドとの構造類似性がなく且つCERT阻害活性に優れる新規化合物を提供することを目的とする。 The present invention has been made in view of such problems, and an object of the present invention is to provide a novel compound having no structural similarity to ceramide and having excellent CERT inhibitory activity.

本発明にかかる新規化合物は、下記構造式(I)からなる。 The novel compound according to the present invention has the following structural formula (I).

Figure 0007060775000001
Figure 0007060775000001

ここで、結合基－Ｘ－は、－Ｃ≡Ｃ－、－ＣＨ２ＣＨ２－、cis－ＣＨ＝ＣＨ－、trans－ＣＨ＝ＣＨ－、cis－シクロプロピル－、又は、trans－シクロプロピル－であり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、及びＲ５は、各々独立して、水素原子、ハロゲン原子、１以上のハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ８アルキル基、又は、ＯＲ６（Ｒ６は、水素原子、又は、ハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ６アルキル基である。）である。 Here, the binding group -X- is -C≡C-, -CH 2 CH 2- , cis-CH = CH-, trans-CH = CH-, cis-cyclopropyl-, or trans-cyclopropyl-. R 1 , R 2 , R 3 , R 4 , and R 5 are linear or branched chains that may independently have a hydrogen atom, a halogen atom, or one or more halogen atoms. A C1-C8 alkyl group or OR 6 (R 6 is a linear or branched C1-C6 alkyl group which may have a hydrogen atom or a halogen atom).

本発明によれば、セラミドとの構造類似性がなく、且つ、CERT阻害活性に優れる新規化合物が得られる。 According to the present invention, a novel compound having no structural similarity to ceramide and having excellent CERT inhibitory activity can be obtained.

E16及びE25につき光学異性体ごとのSM代謝標識率を示す図であり、そのうち(A)はE16-A(1S,2R)であり、(B)はE16-B(1R,2S)であり、(C)はE25-A(1S,2R)であり、(D)はE25-B(1R,2S)である。It is a figure showing the SM metabolism labeling rate for each optical isomer for E16 and E25, of which (A) is E16-A (1S, 2R) and (B) is E16-B (1R, 2S). (C) is E25-A (1S, 2R) and (D) is E25-B (1R, 2S).

以下、添付の図面を参照して本発明の実施形態について具体的に説明するが、当該実施形態は本発明の原理の理解を容易にするためのものであり、本発明の範囲は、下記の実施形態に限られるものではなく、当業者が以下の実施形態の構成を適宜置換した他の実施形態も、本発明の範囲に含まれる。 Hereinafter, embodiments of the present invention will be specifically described with reference to the accompanying drawings, but the embodiments are for facilitating the understanding of the principles of the present invention, and the scope of the present invention is as follows. The present invention is not limited to the embodiments, and other embodiments in which those skilled in the art appropriately replace the configurations of the following embodiments are also included in the scope of the present invention.

本発明にかかる新規化合物は、下記構造式(I)からなる。 The novel compound according to the present invention has the following structural formula (I).

Figure 0007060775000002
Figure 0007060775000002

上記(I)において、結合基－Ｘ－は、－Ｃ≡Ｃ－、－ＣＨ２ＣＨ２－、cis－ＣＨ＝ＣＨ－、trans－ＣＨ＝ＣＨ－、cis－シクロプロピル－、又は、trans－シクロプロピル－である。 In (I) above, the linking group -X- is -C≡C-, -CH 2 CH 2- , cis-CH = CH-, trans-CH = CH-, cis-cyclopropyl-, or trans-. Cyclopropyl-.

上記(I)において、Ｒ１、Ｒ２、Ｒ３、Ｒ４、及びＲ５は、各々独立して、水素原子、ハロゲン原子、１以上のハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ８アルキル基、又は、ＯＲ６（Ｒ６は、水素原子、又は、ハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ６アルキル基である。）である。 In (I) above, R 1 , R 2 , R 3 , R 4 , and R 5 each independently may have a hydrogen atom, a halogen atom, or one or more halogen atoms. A branched C1-C8 alkyl group or OR 6 (R 6 is a linear or branched C1-C6 alkyl group which may have a hydrogen atom or a halogen atom). ..

HPA-12は下記構造式で示され、セラミドと類似の構造を有する。 HPA-12 is represented by the following structural formula and has a structure similar to that of ceramide.

Figure 0007060775000003
Figure 0007060775000003

しかしながら、上記構造式(I)からなる化合物は、セラミドとの類似構造性がほとんどないため、CERT以外へのoff target効果をHPA-12よりも大幅に低減できる。 However, since the compound having the above structural formula (I) has almost no similar structure to ceramide, the off target effect other than CERT can be significantly reduced as compared with HPA-12.

結合基－Ｘ－は、好ましくはcis－シクロプロピル－である。かかる場合、本実施形態にかかる化合物は下記構造式(II)からなる。 The linking group -X- is preferably cis-cyclopropyl-. In such a case, the compound according to this embodiment has the following structural formula (II).

Figure 0007060775000004
Figure 0007060775000004

上記(II)において、Ｒ１、Ｒ２、Ｒ３、Ｒ４、及びＲ５は、各々独立して、水素原子、ハロゲン原子、１以上のハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ８アルキル基、又は、ＯＲ６（Ｒ６は、水素原子、又は、ハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ６アルキル基である。）である。 In (II) above, R 1 , R 2 , R 3 , R 4 , and R 5 each independently have a hydrogen atom, a halogen atom, or a linear or component which may have one or more halogen atoms. A branched C1-C8 alkyl group or OR 6 (R 6 is a linear or branched C1-C6 alkyl group which may have a hydrogen atom or a halogen atom). ..

Ｒ１、Ｒ２、Ｒ３、Ｒ４、及びＲ５において、好ましくは、Ｒ３は鎖状又は環状のＣ５Ｈ８であり、Ｒ１、Ｒ２、Ｒ４、及びＲ５は水素原子である。かかる場合、本実施形態にかかる化合物は下記構造式(III)又は(IV)からなる。 In R 1 , R 2 , R 3 , R 4 , and R 5 , preferably R 3 is a chain or cyclic C 5 H 8 , where R 1 , R 2 , R 4 , and R 5 are hydrogen atoms. Is. In such a case, the compound according to this embodiment has the following structural formula (III) or (IV).

Figure 0007060775000005
Figure 0007060775000005

Figure 0007060775000006
Figure 0007060775000006

上記(III)又は(IV)において、結合基－Ｘ－は、－Ｃ≡Ｃ－、－ＣＨ２ＣＨ２－、cis－ＣＨ＝ＣＨ－、trans－ＣＨ＝ＣＨ－、cis－シクロプロピル－、又は、trans－シクロプロピル－である。 In (III) or (IV) above, the linking group -X- is -C≡C-, -CH 2 CH 2- , cis-CH = CH-, trans-CH = CH-, cis-cyclopropyl-, Alternatively, it is trans-cyclopropyl-.

具体的には、本実施形態にかかる新規化合物は、下記に示す化合物である。 Specifically, the novel compound according to this embodiment is a compound shown below.

化合物Ａ１は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A1, the binding group -X- is -C≡C-, and R 1 , R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000007
Figure 0007060775000007

化合物Ａ２は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ５はＦであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound A2, the binding group -X- is -C≡C-, R5 is F, and R1 , R2 , R3 , and R4 are hydrogen atoms, respectively.

Figure 0007060775000008
Figure 0007060775000008

化合物Ａ３は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ２はＭｅであり、Ｒ１、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A3, the binding group -X- is -C≡C-, R2 is Me, and R1 , R3 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000009
Figure 0007060775000009

化合物Ａ４は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ２はＭｅで、Ｒ５はＦであり、Ｒ１、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound A4, the binding group -X- is -C≡C-, R2 is Me, R5 is F, and R1 , R3 , and R4 are hydrogen atoms, respectively.

Figure 0007060775000010
Figure 0007060775000010

化合物Ａ５は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ４はｔＢｕであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound A5, the binding group -X- is -C≡C-, R4 is tBu, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000011
Figure 0007060775000011

化合物Ａ６は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ４はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound A6, the binding group -X- is -C≡C-, R4 is Me, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000012
Figure 0007060775000012

化合物Ａ７は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ４はＣＦ３であり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound A7, the binding group -X- is -C≡C-, R4 is CF 3 , and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000013
Figure 0007060775000013

化合物Ａ８は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はＭｅであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A8, the binding group -X- is -C≡C- , R3 is Me, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000014
Figure 0007060775000014

化合物Ａ９は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ１はＭｅであり、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A9, the binding group -X- is -C≡C-, R 1 is Me, and R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000015
Figure 0007060775000015

化合物Ａ１０は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ２はＭｅであり、Ｒ３はＭｅであり、Ｒ１、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A10, the binding group -X- is -C≡C-, R2 is Me , R3 is Me, and R1 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000016
Figure 0007060775000016

化合物Ａ１１は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ１はＭｅであり、Ｒ３はＭｅであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A11, the binding group -X- is -C≡C-, R1 is Me , R3 is Me, and R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000017
Figure 0007060775000017

化合物Ａ１２は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ５はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A12, the binding group -X- is -C≡C-, R5 is Me, and R1 , R2 , R3 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000018
Figure 0007060775000018

化合物Ａ１４は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はｎＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A14, the binding group -X- is -C≡C-, R3 is nPr , and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000019
Figure 0007060775000019

化合物Ａ１５は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はＯＥｔであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A15, the binding group -X- is -C≡C- , R3 is OEt, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000020
Figure 0007060775000020

化合物Ａ１６は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はｎＰｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A16, the binding group -X- is -C≡C-, R3 is nPen , and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000021
Figure 0007060775000021

化合物Ａ１７は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はｉＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A17, the binding group -X- is -C≡C- , R3 is iPr, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000022
Figure 0007060775000022

化合物Ａ１８は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はｉＢｕであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A18, the binding group -X- is -C≡C- , R3 is iBu, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000023
Figure 0007060775000023

化合物Ａ１９は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ１はＭｅであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A19, the binding group -X- is -C≡C-, R 1 is Me, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000024
Figure 0007060775000024

化合物Ａ２１は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ１はｎＰｅｎであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A21, the binding group -X- is -C≡C-, R 1 is nPen, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000025
Figure 0007060775000025

化合物Ａ２２は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はＨｅｐであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A22, the binding group -X- is -C≡C- , R3 is Hep, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000026
Figure 0007060775000026

化合物Ａ２３は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はＯｃｔａであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A23, the binding group -X- is -C≡C- , R3 is Octa, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000027
Figure 0007060775000027

化合物Ａ２４は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はｃ－Ｈｅｘであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A24, the binding group -X- is -C≡C-, R3 is c - Hex, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000028
Figure 0007060775000028

化合物Ａ２５は、結合基－Ｘ－は－Ｃ≡Ｃ－であり、Ｒ３はｃ－Ｐｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound A25, the binding group -X- is -C≡C-, R3 is c - Pen, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000029
Figure 0007060775000029

化合物Ｂ１は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B1, the binding group -X- is -CH 2 CH 2- , and R 1 , R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000030
Figure 0007060775000030

化合物Ｂ２は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ５はＦであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound B2, the binding group -X- is -CH 2 CH 2- , R 5 is F, and R 1 , R 2 , R 3 and R 4 are hydrogen atoms, respectively.

Figure 0007060775000031
Figure 0007060775000031

化合物Ｂ３は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ２はＭｅであり、Ｒ１、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B3, the binding group -X- is -CH 2 CH 2- , R 2 is Me, and R 1 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000032
Figure 0007060775000032

化合物Ｂ４は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ２はＭｅで、Ｒ５はＦであり、Ｒ１、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound B4, the binding group -X- is -CH 2 CH 2- , R 2 is Me, R 5 is F, and R 1 , R 3 , and R 4 are hydrogen atoms, respectively.

Figure 0007060775000033
Figure 0007060775000033

化合物Ｂ５は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ４はｔＢｕであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound B5, the binding group -X- is -CH 2 CH 2- , R 4 is tBu, and R 1 , R 2 , R 3 and R 5 are hydrogen atoms, respectively.

Figure 0007060775000034
Figure 0007060775000034

化合物Ｂ６は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ４はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound B6, the binding group -X- is -CH 2 CH 2- , R 4 is Me, and R 1 , R 2 , R 3 and R 5 are hydrogen atoms, respectively.

Figure 0007060775000035
Figure 0007060775000035

化合物Ｂ７は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ４はＣＦ３であり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound B7, the binding group -X- is -CH 2 CH 2- , R 4 is CF 3 , and R 1 , R 2 , R 3 and R 5 are hydrogen atoms, respectively.

Figure 0007060775000036
Figure 0007060775000036

化合物Ｂ８は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はＭｅであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B8, the binding group -X- is -CH 2 CH 2- , R 3 is Me, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000037
Figure 0007060775000037

化合物Ｂ９は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ１はＭｅであり、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B9, the binding group -X- is -CH 2 CH 2- , R 1 is Me, and R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000038
Figure 0007060775000038

化合物Ｂ１０は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ２はＭｅであり、Ｒ３はＭｅであり、Ｒ１、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B10, the binding group -X- is -CH 2 CH 2- , R 2 is Me, R 3 is Me, and R 1 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000039
Figure 0007060775000039

化合物Ｂ１１は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ１はＭｅであり、Ｒ３はＭｅであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B11, the binding group -X- is -CH 2 CH 2- , R 1 is Me, R 3 is Me, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000040
Figure 0007060775000040

化合物Ｂ１２は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ５はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B12, the binding group -X- is -CH 2 CH 2- , R 5 is Me, and R 1 , R 2, R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000041
Figure 0007060775000041

化合物Ｂ１４は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はｎＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B14, the binding group -X- is -CH 2 CH 2- , R 3 is nPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000042
Figure 0007060775000042

化合物Ｂ１５は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はＯＥｔであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B15, the binding group -X- is -CH 2 CH 2- , R 3 is OEt, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000043
Figure 0007060775000043

化合物Ｂ１６は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はｎＰｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B16, the binding group -X- is -CH 2 CH 2- , R 3 is nPen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000044
Figure 0007060775000044

化合物Ｂ１７は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はｉＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B17, the binding group -X- is -CH 2 CH 2- , R 3 is iPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000045
Figure 0007060775000045

化合物Ｂ１８は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はｉＢｕであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B18, the binding group -X- is -CH 2 CH 2- , R 3 is iBu, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000046
Figure 0007060775000046

化合物Ｂ１９は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ１はＭｅであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B19, the binding group -X- is -CH 2 CH 2- , R 1 is Me, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000047
Figure 0007060775000047

化合物Ｂ２１は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ１はｎＰｅｎであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B21, the binding group -X- is -CH 2 CH 2- , R 1 is nPen, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000048
Figure 0007060775000048

化合物Ｂ２２は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はＨｅｐであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B22, the binding group -X- is -CH 2 CH 2- , R 3 is Hep, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000049
Figure 0007060775000049

化合物Ｂ２３は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はＯｃｔａであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B23, the binding group -X- is -CH 2 CH 2- , R 3 is Octa, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000050
Figure 0007060775000050

化合物Ｂ２４は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はｃ－Ｈｅｘであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B24, the binding group -X- is -CH 2 CH 2- , R 3 is c-Hex, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000051
Figure 0007060775000051

化合物Ｂ２５は、結合基－Ｘ－は－ＣＨ２ＣＨ２－であり、Ｒ３はｃ－Ｐｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound B25, the binding group -X- is -CH 2 CH 2- , R 3 is c-Pen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000052
Figure 0007060775000052

化合物Ｃ１は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C1, the bonding group -X- is cis-CH = CH-, and R 1 , R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000053
Figure 0007060775000053

化合物Ｃ２は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ５はＦであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound C2, the binding group -X- is cis - CH = CH-, R5 is F, and R1 , R2 , R3 , and R4 are hydrogen atoms, respectively.

Figure 0007060775000054
Figure 0007060775000054

化合物Ｃ３は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ２はＭｅであり、Ｒ１、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C3, the binding group -X- is cis-CH = CH-, R 2 is Me, and R 1 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000055
Figure 0007060775000055

化合物Ｃ４は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ２はＭｅで、Ｒ５はＦであり、Ｒ１、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound C4, the binding group -X- is cis - CH = CH-, R2 is Me, R5 is F, and R1 , R3 , and R4 are hydrogen atoms, respectively.

Figure 0007060775000056
Figure 0007060775000056

化合物Ｃ５は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ４はｔＢｕであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound C5, the binding group -X- is cis - CH = CH-, R4 is tBu, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000057
Figure 0007060775000057

化合物Ｃ６は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ４はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound C6, the binding group -X- is cis - CH = CH-, R4 is Me, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000058
Figure 0007060775000058

化合物Ｃ７は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ４はＣＦ３であり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound C7, the binding group -X- is cis - CH = CH-, R4 is CF3 , and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000059
Figure 0007060775000059

化合物Ｃ８は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はＭｅであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C8, the binding group -X- is cis-CH = CH-, R 3 is Me, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000060
Figure 0007060775000060

化合物Ｃ９は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ１はＭｅであり、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C9, the binding group -X- is cis-CH = CH-, R 1 is Me, and R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000061
Figure 0007060775000061

化合物Ｃ１０は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ２はＭｅであり、Ｒ３はＭｅであり、Ｒ１、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C10, the binding group -X- is cis-CH = CH-, R 2 is Me, R 3 is Me, and R 1 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000062
Figure 0007060775000062

化合物Ｃ１１は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ１はＭｅであり、Ｒ３はＭｅであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C11, the binding group -X- is cis-CH = CH-, R 1 is Me, R 3 is Me, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000063
Figure 0007060775000063

化合物Ｃ１２は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ５はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C12, the binding group -X- is cis-CH = CH-, R 5 is Me, and R 1 , R 2, R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000064
Figure 0007060775000064

化合物Ｃ１４は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はｎＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C14, the binding group -X- is cis-CH = CH-, R 3 is nPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000065
Figure 0007060775000065

化合物Ｃ１５は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はＯＥｔであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C15, the binding group -X- is cis-CH = CH-, R 3 is OEt, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000066
Figure 0007060775000066

化合物Ｃ１６は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はｎＰｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C16, the binding group -X- is cis-CH = CH-, R 3 is nPen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000067
Figure 0007060775000067

化合物Ｃ１７は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はｉＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C17, the binding group -X- is cis-CH = CH-, R 3 is iPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000068
Figure 0007060775000068

化合物Ｃ１８は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はｉＢｕであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C18, the binding group -X- is cis-CH = CH-, R 3 is iBu, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000069
Figure 0007060775000069

化合物Ｃ１９は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ１はＭｅであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C19, the binding group -X- is cis-CH = CH-, R 1 is Me, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000070
Figure 0007060775000070

化合物Ｃ２１は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ１はｎＰｅｎであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C21, the binding group -X- is cis-CH = CH-, R 1 is nPen, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000071
Figure 0007060775000071

化合物Ｃ２２は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はＨｅｐであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C22, the binding group -X- is cis-CH = CH-, R 3 is Hep, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000072
Figure 0007060775000072

化合物Ｃ２３は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はＯｃｔａであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C23, the binding group -X- is cis-CH = CH-, R 3 is Octa, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000073
Figure 0007060775000073

化合物Ｃ２４は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はｃ－Ｈｅｘであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C24, the binding group -X- is cis-CH = CH-, R3 is c - Hex, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000074
Figure 0007060775000074

化合物Ｃ２５は、結合基－Ｘ－はcis－ＣＨ＝ＣＨ－であり、Ｒ３はｃ－Ｐｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound C25, the binding group -X- is cis-CH = CH-, R 3 is c-Pen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000075
Figure 0007060775000075

化合物Ｄ１は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D1, the binding group -X- is trans-CH = CH-, and R 1 , R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000076
Figure 0007060775000076

化合物Ｄ２は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ５はＦであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound D2, the binding group -X- is trans - CH = CH-, R5 is F, and R1 , R2 , R3 , and R4 are hydrogen atoms, respectively.

Figure 0007060775000077
Figure 0007060775000077

化合物Ｄ３は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ２はＭｅであり、Ｒ１、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D3, the binding group -X- is trans-CH = CH-, R 2 is Me, and R 1 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000078
Figure 0007060775000078

化合物Ｄ４は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ２はＭｅで、Ｒ５はＦであり、Ｒ１、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound D4, the binding group -X- is trans-CH = CH-, R 2 is Me, R 5 is F, and R 1 , R 3 , and R 4 are hydrogen atoms, respectively.

Figure 0007060775000079
Figure 0007060775000079

化合物Ｄ５は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ４はｔＢｕであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound D5, the binding group -X- is trans - CH = CH-, R4 is tBu, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000080
Figure 0007060775000080

化合物Ｄ６は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ４はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound D6, the binding group -X- is trans - CH = CH-, R4 is Me, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000081
Figure 0007060775000081

化合物Ｄ７は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ４はＣＦ３であり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound D7, the binding group -X- is trans-CH = CH-, R 4 is CF 3 , and R 1 , R 2 , R 3 and R 5 are hydrogen atoms, respectively.

Figure 0007060775000082
Figure 0007060775000082

化合物Ｄ８は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はＭｅであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D8, the binding group -X- is trans-CH = CH-, R 3 is Me, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000083
Figure 0007060775000083

化合物Ｄ９は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ１はＭｅであり、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D9, the binding group -X- is trans-CH = CH-, R 1 is Me, and R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000084
Figure 0007060775000084

化合物Ｄ１０は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ２はＭｅであり、Ｒ３はＭｅであり、Ｒ１、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D10, the binding group -X- is trans-CH = CH-, R 2 is Me, R 3 is Me, and R 1 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000085
Figure 0007060775000085

化合物Ｄ１１は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ１はＭｅであり、Ｒ３はＭｅであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D11, the binding group -X- is trans-CH = CH-, R 1 is Me, R 3 is Me, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000086
Figure 0007060775000086

化合物Ｄ１２は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ５はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D12, the binding group -X- is trans-CH = CH-, R 5 is Me, and R 1 , R 2, R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000087
Figure 0007060775000087

化合物Ｄ１４は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はｎＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D14, the binding group -X- is trans-CH = CH-, R 3 is nPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000088
Figure 0007060775000088

化合物Ｄ１５は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はＯＥｔであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D15, the binding group -X- is trans-CH = CH-, R 3 is OEt, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000089
Figure 0007060775000089

化合物Ｄ１６は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はｎＰｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D16, the binding group -X- is trans-CH = CH-, R 3 is nPen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000090
Figure 0007060775000090

化合物Ｄ１７は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はｉＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D17, the binding group -X- is trans-CH = CH-, R 3 is iPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000091
Figure 0007060775000091

化合物Ｄ１８は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はｉＢｕであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D18, the binding group -X- is trans-CH = CH-, R 3 is iBu, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000092
Figure 0007060775000092

化合物Ｄ１９は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ１はＭｅであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D19, the binding group -X- is trans-CH = CH-, R 1 is Me, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000093
Figure 0007060775000093

化合物Ｄ２１は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ１はｎＰｅｎであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D21, the binding group -X- is trans-CH = CH-, R 1 is nPen, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000094
Figure 0007060775000094

化合物Ｄ２２は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はＨｅｐであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D22, the binding group -X- is trans-CH = CH-, R 3 is Hep, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000095
Figure 0007060775000095

化合物Ｄ２３は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はＯｃｔａであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D23, the binding group -X- is trans-CH = CH-, R 3 is Octa, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000096
Figure 0007060775000096

化合物Ｄ２４は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はｃ－Ｈｅｘであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D24, the binding group -X- is trans-CH = CH-, R 3 is c-Hex, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000097
Figure 0007060775000097

化合物Ｄ２５は、結合基－Ｘ－はtrans－ＣＨ＝ＣＨ－であり、Ｒ３はｃ－Ｐｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound D25, the binding group -X- is trans-CH = CH-, R 3 is c-Pen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000098
Figure 0007060775000098

化合物Ｅ１は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。なお、本実施形態にかかる化合物Ｅ１は、一方の異性体、他方の異性体、及び、ラセミ体の全てを含むものである。化合物Ｅ２～Ｅ２５も、一方の異性体、他方の異性体、及び、ラセミ体の全てを含むものであるが、一方の異性体のみを記載し、それ以外は省略するものとする。 In compound E1, the linking group -X- is cis-cyclopropyl-, and R 1 , R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively. The compound E1 according to the present embodiment contains all of one isomer, the other isomer, and racemate. Compounds E2 to E25 also include all of one isomer, the other isomer, and racemate, but only one isomer is described, and the others are omitted.

Figure 0007060775000099
Figure 0007060775000099

Figure 0007060775000100
Figure 0007060775000100

Figure 0007060775000101
Figure 0007060775000101

化合物Ｅ２は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ５はＦであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound E2, the linking group -X- is cis - cyclopropyl-, R5 is F, and R1 , R2 , R3 , and R4 are hydrogen atoms, respectively.

Figure 0007060775000102
Figure 0007060775000102

化合物Ｅ３は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ２はＭｅであり、Ｒ１、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E3, the linking group -X- is cis-cyclopropyl-, R 2 is Me, and R 1 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000103
Figure 0007060775000103

化合物Ｅ４は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ２はＭｅで、Ｒ５はＦであり、Ｒ１、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound E4, the linking group-X- is cis - cyclopropyl-, R2 is Me, R5 is F, and R1 , R3 , and R4 are hydrogen atoms, respectively.

Figure 0007060775000104
Figure 0007060775000104

化合物Ｅ５は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ４はｔＢｕであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound E5, the linking group -X- is cis - cyclopropyl-, R4 is tBu, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000105
Figure 0007060775000105

化合物Ｅ６は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ４はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound E6, the linking group-X- is cis - cyclopropyl-, R4 is Me, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000106
Figure 0007060775000106

化合物Ｅ７は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ４はＣＦ３であり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound E7, the linking group-X- is cis - cyclopropyl-, R4 is CF3 , and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000107
Figure 0007060775000107

化合物Ｅ８は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はＭｅであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である In compound E8, the linking group -X- is cis-cyclopropyl-, R 3 is Me, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000108
Figure 0007060775000108

化合物Ｅ９は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ１はＭｅであり、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E9, the linking group -X- is cis-cyclopropyl-, R 1 is Me, and R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000109
Figure 0007060775000109

化合物Ｅ１０は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ２はＭｅであり、Ｒ３はＭｅであり、Ｒ１、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E10, the linking group -X- is cis-cyclopropyl-, R 2 is Me, R 3 is Me, and R 1 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000110
Figure 0007060775000110

化合物Ｅ１１は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ１はＭｅであり、Ｒ３はＭｅであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E11, the linking group -X- is cis-cyclopropyl-, R 1 is Me, R 3 is Me, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000111
Figure 0007060775000111

化合物Ｅ１２は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ５はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E12, the linking group -X- is cis-cyclopropyl-, R 5 is Me, and R 1 , R 2, R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000112
Figure 0007060775000112

化合物Ｅ１４は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はｎＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E14, the linking group -X- is cis-cyclopropyl-, R 3 is nPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000113
Figure 0007060775000113

化合物Ｅ１５は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はＯＥｔであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E15, the linking group -X- is cis-cyclopropyl-, R 3 is OEt, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000114
Figure 0007060775000114

化合物Ｅ１６は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はｎＰｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E16, the linking group -X- is cis-cyclopropyl-, R 3 is nPen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000115
Figure 0007060775000115

化合物Ｅ１７は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はｉＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E17, the linking group -X- is cis-cyclopropyl-, R 3 is iPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000116
Figure 0007060775000116

化合物Ｅ１８は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はｉＢｕであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E18, the linking group -X- is cis-cyclopropyl-, R 3 is iBu, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000117
Figure 0007060775000117

化合物Ｅ１９は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ１はＭｅであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E19, the linking group -X- is cis-cyclopropyl-, R 1 is Me, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000118
Figure 0007060775000118

化合物Ｅ２１は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ１はｎＰｅｎであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E21, the linking group -X- is cis-cyclopropyl-, R 1 is nPen, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000119
Figure 0007060775000119

化合物Ｅ２２は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はＨｅｐであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E22, the linking group -X- is cis-cyclopropyl-, R 3 is Hep, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000120
Figure 0007060775000120

化合物Ｅ２３は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はＯｃｔａであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E23, the linking group -X- is cis-cyclopropyl-, R 3 is Octa, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000121
Figure 0007060775000121

化合物Ｅ２４は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はｃ－Ｈｅｘであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E24, the linking group-X- is cis-cyclopropyl-, R3 is c - Hex, and R1 , R2 , R4 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000122
Figure 0007060775000122

化合物Ｅ２５は、結合基－Ｘ－はcis－シクロプロピル－であり、Ｒ３はｃ－Ｐｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound E25, the linking group -X- is cis-cyclopropyl-, R 3 is c-Pen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000123
Figure 0007060775000123

化合物Ｆ１は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。なお、本実施形態にかかる化合物Ｆ１は、一方の異性体、他方の異性体、及び、ラセミ体の全てを含むものである。化合物Ｆ２～Ｆ２５も、一方の異性体、他方の異性体、及び、ラセミ体の全てを含むものであるが、一方の異性体のみを記載し、それ以外は省略するものとする。 In compound F1, the linking group -X- is trans-cyclopropyl-, and R 1 , R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively. The compound F1 according to the present embodiment contains all of one isomer, the other isomer, and racemate. Compounds F2 to F25 also include all of one isomer, the other isomer, and racemate, but only one isomer is described, and the others are omitted.

Figure 0007060775000124
Figure 0007060775000124

Figure 0007060775000125
Figure 0007060775000125

Figure 0007060775000126
Figure 0007060775000126

化合物Ｆ２は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ５はＦであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound F2, the linking group -X- is trans - cyclopropyl-, R5 is F, and R1 , R2 , R3 , and R4 are hydrogen atoms, respectively.

Figure 0007060775000127
Figure 0007060775000127

化合物Ｆ３は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ２はＭｅであり、Ｒ１、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F3, the linking group -X- is trans-cyclopropyl-, R 2 is Me, and R 1 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000128
Figure 0007060775000128

化合物Ｆ４は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ２はＭｅで、Ｒ５はＦであり、Ｒ１、Ｒ３、Ｒ４はそれぞれ水素原子である。 In compound F4, the linking group -X- is trans-cyclopropyl-, R 2 is Me, R 5 is F, and R 1 , R 3 , and R 4 are hydrogen atoms, respectively.

Figure 0007060775000129
Figure 0007060775000129

化合物Ｆ５は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ４はｔＢｕであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound F5, the linking group-X- is trans - cyclopropyl-, R4 is tBu, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000130
Figure 0007060775000130

化合物Ｆ６は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ４はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound F6, the linking group-X- is trans - cyclopropyl-, R4 is Me, and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000131
Figure 0007060775000131

化合物Ｆ７は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ４はＣＦ３であり、Ｒ１、Ｒ２、Ｒ３、Ｒ５はそれぞれ水素原子である。 In compound F7, the linking group-X- is trans - cyclopropyl-, R4 is CF3 , and R1 , R2 , R3 , and R5 are hydrogen atoms, respectively.

Figure 0007060775000132
Figure 0007060775000132

化合物Ｆ８は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はＭｅであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F8, the linking group -X- is trans-cyclopropyl-, R 3 is Me, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000133
Figure 0007060775000133

化合物Ｆ９は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ１はＭｅであり、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F9, the linking group -X- is trans-cyclopropyl-, R 1 is Me, and R 2 , R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000134
Figure 0007060775000134

化合物Ｆ１０は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ２はＭｅであり、Ｒ３はＭｅであり、Ｒ１、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F10, the linking group -X- is trans-cyclopropyl-, R 2 is Me, R 3 is Me, and R 1 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000135
Figure 0007060775000135

化合物Ｆ１１は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ１はＭｅであり、Ｒ３はＭｅであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F11, the linking group -X- is trans-cyclopropyl-, R 1 is Me, R 3 is Me, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000136
Figure 0007060775000136

化合物Ｆ１２は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ５はＭｅであり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F12, the linking group -X- is trans-cyclopropyl-, R 5 is Me, and R 1 , R 2, R 3 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000137
Figure 0007060775000137

化合物Ｆ１４は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はｎＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F14, the linking group -X- is trans-cyclopropyl-, R 3 is nPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000138
Figure 0007060775000138

化合物Ｆ１５は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はＯＥｔであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F15, the linking group -X- is trans-cyclopropyl-, R 3 is OEt, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000139
Figure 0007060775000139

化合物Ｆ１６は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はｎＰｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F16, the linking group -X- is trans-cyclopropyl-, R 3 is nPen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000140
Figure 0007060775000140

化合物Ｆ１７は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はｉＰｒであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F17, the linking group -X- is trans-cyclopropyl-, R 3 is iPr, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000141
Figure 0007060775000141

化合物Ｆ１８は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はｉＢｕであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F18, the linking group -X- is trans-cyclopropyl-, R 3 is iBu, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000142
Figure 0007060775000142

化合物Ｆ１９は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ１はＭｅであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F19, the linking group -X- is trans-cyclopropyl-, R 1 is Me, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000143
Figure 0007060775000143

化合物Ｆ２１は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ１はｎＰｅｎであり、Ｒ３はｎＰｒであり、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F21, the linking group -X- is trans-cyclopropyl-, R 1 is nPen, R 3 is nPr, and R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000144
Figure 0007060775000144

化合物Ｆ２２は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はＨｅｐであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F22, the linking group -X- is trans-cyclopropyl-, R 3 is Hep, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000145
Figure 0007060775000145

化合物Ｆ２３は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はＯｃｔａであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F23, the linking group -X- is trans-cyclopropyl-, R 3 is Octa, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000146
Figure 0007060775000146

化合物Ｆ２４は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はｃ－Ｈｅｘであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F24, the linking group -X- is trans-cyclopropyl-, R 3 is c-Hex, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000147
Figure 0007060775000147

化合物Ｆ２５は、結合基－Ｘ－はtrans－シクロプロピル－であり、Ｒ３はｃ－Ｐｅｎであり、Ｒ１、Ｒ２、Ｒ４、Ｒ５はそれぞれ水素原子である。 In compound F25, the linking group -X- is trans-cyclopropyl-, R 3 is c-Pen, and R 1 , R 2 , R 4, and R 5 are hydrogen atoms, respectively.

Figure 0007060775000148
Figure 0007060775000148

本実施形態にかかるCERT機能阻害剤は、本実施形態にかかる新規化合物を含み、CERTのSTARTドメインに結合してCERT機能を阻害する。 The CERT function inhibitor according to this embodiment contains a novel compound according to this embodiment, and binds to the START domain of CERT to inhibit CERT function.

本実施形態にかかる医薬組成物は、医薬的に有効量の本実施形態にかかる新規化合物を含み、感染症を治療又は予防するための医薬組成物である。例えば、本実施形態にかかる新規化合物は、CERTの機能を阻害してスィンゴ脂質の合成を阻害するため、HCVゲノム複製阻害だけでなく粒子形成あるいは感染過程も阻害可能である。そのためHCVを治療又は予防するための医薬組成物として使用できる。 The pharmaceutical composition according to the present embodiment contains a pharmaceutically effective amount of the novel compound according to the present embodiment, and is a pharmaceutical composition for treating or preventing an infectious disease. For example, since the novel compound according to this embodiment inhibits the function of CERT and inhibits the synthesis of singolipid, it can inhibit not only HCV genome replication inhibition but also particle formation or infection process. Therefore, it can be used as a pharmaceutical composition for treating or preventing HCV.

本実施形態にかかる医薬組成物は、医薬的に有効量の本実施形態にかかる新規化合物を含み、がんを治療又は予防するための医薬組成物である。例えば、化学療法剤に対して耐性を獲得したがん細胞のCERTを阻害すると、がん細胞はの化学療法剤に対する再感作(resensitization)を起こす。そのためがんを治療又は予防するための医薬組成物として使用可能である。 The pharmaceutical composition according to the present embodiment contains a pharmaceutically effective amount of the novel compound according to the present embodiment, and is a pharmaceutical composition for treating or preventing cancer. For example, inhibition of CERT in cancer cells that have acquired resistance to chemotherapeutic agents causes the cancer cells to resensitize to the chemotherapeutic agents. Therefore, it can be used as a pharmaceutical composition for treating or preventing cancer.

本発明の医薬組成物は、注射、急速注入、鼻咽頭吸収、皮膚吸収により、非経口的に、および経口的に投与し得る。非経口投与のための製薬上許容可能な担体調製物としては、滅菌、あるいは水性または非水性の溶液、懸濁液および乳濁液が挙げられる。非水性溶媒の例は、プロピレングリコール、ポリエチレングリコール、植物油、例えばオリーブ油、注射可能有機エステル、例えばエチルオレエートである。閉塞性包帯用の担体は、皮膚透過性を増大し、抗原吸収を増強するために用い得る。経口投与のための液体投薬形態は、液体投薬形態を含有するリポソーム溶液を包含し得る。 The pharmaceutical composition of the present invention can be administered parenterally and orally by injection, rapid infusion, nasopharyngeal absorption, skin absorption. Pharmaceutically acceptable carrier preparations for parenteral administration include sterile or aqueous or non-aqueous solutions, suspensions and emulsions. Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable organic esters such as ethyloleate. Carriers for obstructive bandages can be used to increase skin permeability and enhance antigen absorption. Liquid dosage forms for oral administration may include liposome solutions containing liquid dosage forms.

本発明の医薬組成物は、アジュバントを含有することも可能である。アジュバントは、特異的免疫応答を非特異的に増大するために用い得る物質である。アジュバントは、それらの粗製に基づいて、大まかにいくつかの群に分けられる。 The pharmaceutical composition of the present invention can also contain an adjuvant. An adjuvant is a substance that can be used to non-specifically increase a specific immune response. The adjuvants are roughly divided into several groups based on their crudeness.

これらの群としては、油アジュバント（例えば、フロイントの完全および不完全アジュバント）、無機塩（例えば、AlK(SO4)2、AlNH4(SO4)、シリカ、ミョウバン、Al(OH)3、Ca3(PO4)2、カオリンおよび炭素）、ポリヌクレオチド（例えばポリICおよびポリAU酸）が挙げられる。 These groups include oil adjuvants (eg, Freund's complete and incomplete adjuvants), inorganic salts (eg, AlK (SO 4 ) 2 , AlNH 4 (SO 4 ), silica, alum, Al (OH) 3 , Ca. 3 (PO 4 ) 2 , kaolin and carbon), polynucleotides (eg poly IC and poly AU acid).

下記合成法により本実施例にかかる化合物を合成した。 The compound according to this example was synthesized by the following synthetic method.

(1)Ａ１～Ａ２５の合成
Ａ１～Ａ２５の合成は下記合成法により合成した。 (1) Synthesis of A1 to A25 The synthesis of A1 to A25 was synthesized by the following synthetic method.

Figure 0007060775000149
Figure 0007060775000149

ここでL1(R1及びR2がともに水素原子)は市販品を使用した。 Here, a commercially available product was used for L1 (both R1 and R2 are hydrogen atoms).

2-ethynyl-6-methylpyridine(L2)は、下記合成法により合成した。 2-ethynyl-6-methylpyridine (L2) was synthesized by the following synthetic method.

Figure 0007060775000150
Figure 0007060775000150

2-ethynyl-3-methylpyridine(L3)は、下記合成法により合成した。 2-ethynyl-3-methylpyridine (L3) was synthesized by the following synthetic method.

Figure 0007060775000151
Figure 0007060775000151

2-ethynyl-3-pentylpyridine(L4)は、下記合成法により合成した。 2-ethynyl-3-pentylpyridine (L4) was synthesized by the following synthetic method.

Figure 0007060775000152
Figure 0007060775000152

3-Iodobenzeneboronic acid pinacol ester(M1)は、下記合成法により合成した。 3-Iodobenzeneboronic acid pinacol ester (M1) was synthesized by the following synthetic method.

Figure 0007060775000153
Figure 0007060775000153

2-fluoro-5-iodobenzeneboronic acid pinacol ester(M2)は、下記合成法により合成した。 2-fluoro-5-iodobenzeneboronic acid pinacol ester (M2) was synthesized by the following synthetic method.

Figure 0007060775000154
Figure 0007060775000154

3-(tert-butyl)-5-iodobenzeneboronic acid pinacol ester(M3)、5-iodo-3-methylbenzeneboronic acid pinacol ester(M4)、及び、5-iodo-3-(trifluoromethyl)benzeneboronic acid pinacol ester(M5)は、下記合成法により合成した。 3- (tert-butyl) -5-iodobenzeneboronic acid pinacol ester (M3), 5-iodo-3-methylbenzeneboronic acid pinacol ester (M4), and 5-iodo-3- (trifluoromethyl) benzeneboronic acid pinacol ester (M5) Was synthesized by the following synthetic method.

Figure 0007060775000155
Figure 0007060775000155

3-iodo-4-methylbenzeneboronic acid pinacol ester(M6)は、下記合成法により合成した。 3-iodo-4-methylbenzeneboronic acid pinacol ester (M6) was synthesized by the following synthetic method.

Figure 0007060775000156
Figure 0007060775000156

3-Iodo-6-methylbenzeneboronic acid pinacol ester(M7)は、下記合成法により合成した。 3-Iodo-6-methylbenzeneboronic acid pinacol ester (M7) was synthesized by the following synthetic method.

Figure 0007060775000157
Figure 0007060775000157

3-Iodo-4-propylbenzeneboronic acid pinacol ester(M8)、3-Iodo-4-pentylbenzeneboronic acid pinacol ester(M9)、3-Iodo-4-isopropylbenzeneboronic acid pinacol ester(M10)、3-Iodo-4-isobutylbenzeneboronic acid pinacol ester(M11)、3-Iodo-4-heptylbenzeneboronic acid pinacol ester(M12)、及び、3-Iodo-4-octylbenzeneboronic acid pinacol ester(M13)は、下記合成法により合成した。 3-Iodo-4-propylbenzeneboronic acid pinacol ester (M8), 3-Iodo-4-pentylbenzeneboronic acid pinacol ester (M9), 3-Iodo-4-isopropylbenzeneboronic acid pinacol ester (M10), 3-Iodo-4-isobutylbenzeneboronic acid The pinacol ester (M11), 3-Iodo-4-heptylbenzeneboronic acid pinacol ester (M12), and 3-Iodo-4-octylbenzeneboronic acid pinacol ester (M13) were synthesized by the following synthetic methods.

Figure 0007060775000158
Figure 0007060775000158

3-Iodo-4-cyclohexylbenzeneboronic acid pinacol ester(M14)、及び、3-Iodo-4-cyclopentylbenzeneboronic acid pinacol ester(M15)は、下記合成法により合成した。 3-Iodo-4-cyclohexylbenzeneboronic acid pinacol ester (M14) and 3-Iodo-4-cyclopentylbenzeneboronic acid pinacol ester (M15) were synthesized by the following synthetic methods.

Figure 0007060775000159
Figure 0007060775000159

4-Hydroxyethylsulfonylbromobenzene(R1)は、下記合成法により合成した。 4-Hydroxyethylsulfonylbromobenzene (R1) was synthesized by the following synthetic method.

Figure 0007060775000160
Figure 0007060775000160

合成したA1～A25のNMRを下記に示す。 The synthesized NMR of A1 to A25 is shown below.

4'-(2-hydroxyethanesulfonyl)-3-(pyridin-2-ylethynyl)-1,1'-biphenyl (A1) 1H-NMR (CDCl3) δ: 8.65-8.63 (1H, m), 8.02-8.00 (2H, m), 7.86 (1H, dd, J = 2.3, 1.1 Hz), 7.79 (2H, dt, J= 8.8, 1.9 Hz), 7.72 (1H, td, J = 7.8, 1.9 Hz), 7.68-7.65 (1H, m), 7.62 (1H, tt, J = 5.0, 1.9 Hz), 7.56 (1H, dt, J = 7.9, 1.0 Hz), 7.50 (1H, t, J = 7.8 Hz), 7.28 (1H, ddd, J = 7.3, 4.7, 1.4 Hz), 4.06 (2H, dt, J = 10.9, 5.9 Hz), 3.42 (2H, dt, J = 4.1, 2.0 Hz), 2.97 (1H, t, J = 6.3 Hz).; 13C-NMR (CDCl3) δ: 56.4, 58.4, 88.4, 89.3, 123.0, 123.3, 127.2, 127.9, 128.0, 128.6, 129.3, 131.0, 132.1, 136.3, 137.9, 139.2, 143.1, 145.9, 150.1. 4'-(2-hydroxyethanesulfonyl) -3- (pyridin-2-ylethynyl) -1,1'-biphenyl (A1) 1 H-NMR (CDCl 3 ) δ: 8.65-8.63 (1H, m), 8.02-8.00 (2H, m), 7.86 (1H, dd, J = 2.3, 1.1 Hz), 7.79 (2H, dt, J = 8.8, 1.9 Hz), 7.72 (1H, td, J = 7.8, 1.9 Hz), 7.68- 7.65 (1H, m), 7.62 (1H, tt, J = 5.0, 1.9 Hz), 7.56 (1H, dt, J = 7.9, 1.0 Hz), 7.50 (1H, t, J = 7.8 Hz), 7.28 (1H) , ddd, J = 7.3, 4.7, 1.4 Hz), 4.06 (2H, dt, J = 10.9, 5.9 Hz), 3.42 (2H, dt, J = 4.1, 2.0 Hz), 2.97 (1H, t, J = 6.3) Hz) .; 13 C-NMR (CDCl 3 ) δ: 56.4, 58.4, 88.4, 89.3, 123.0, 123.3, 127.2, 127.9, 128.0, 128.6, 129.3, 131.0, 132.1, 136.3, 137.9, 139.2, 143.1, 145.9, 150.1.

2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A2) 1H-NMR (CDCl3) δ: 8.63 (1H, dt, J= 4.6, 1.6 Hz), 8.03 (2H, dt, J = 8.7, 2.1 Hz), 7.79-7.76 (2H, m), 7.74-7.62 (3H, m), 7.55-7.46 (2H, m), 7.28 (1H, ddd, J = 7.4, 4.7, 1.5 Hz), 7.22 (1H, dd, J = 10.5, 8.7 Hz), 4.06 (2H, s), 3.42 (2H, td, J= 4.1, 2.0 Hz), 3.05 (1H, s).; 13C-NMR (CDCl3) δ: 56.3, 58.3, 87.4, 89.0, 116.9 (d, J = 23.0 Hz), 119.2 (d, J = 3.8 Hz), 123.1, 127.2 (d, J= 18.2 Hz), 128.3, 128.5 (d, J = 11.5 Hz), 130.0 (d, J = 3.8 Hz), 132.0 (d, J = 5.8 Hz), 134.1 (d, J = 8.6 Hz), 134.4 (d, J= 2.9 Hz), 136.3, 138.3, 140.6, 142.9, 150.1. 158.4, 161.0. 2-fluoro-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A2) 1 H-NMR (CDCl 3 ) δ: 8.63 (1H, dt, J = 4.6, 1.6 Hz), 8.03 (2H, dt, J = 8.7, 2.1 Hz), 7.79-7.76 (2H, m), 7.74-7.62 (3H, m), 7.55-7.46 (2H, m), 7.28 (1H) , ddd, J = 7.4, 4.7, 1.5 Hz), 7.22 (1H, dd, J = 10.5, 8.7 Hz), 4.06 (2H, s), 3.42 (2H, td, J = 4.1, 2.0 Hz), 3.05 ( 1H, s) .; 13 C-NMR (CDCl 3 ) δ: 56.3, 58.3, 87.4, 89.0, 116.9 (d, J = 23.0 Hz), 119.2 (d, J = 3.8 Hz), 123.1, 127.2 (d, J = 18.2 Hz), 128.3, 128.5 (d, J = 11.5 Hz), 130.0 (d, J = 3.8 Hz), 132.0 (d, J = 5.8 Hz), 134.1 (d, J = 8.6 Hz), 134.4 ( d, J = 2.9 Hz), 136.3, 138.3, 140.6, 142.9, 150.1. 158.4, 161.0.

4'-(2-hydroxyethanesulfonyl)-3-(6-methylpyridin-2-yl)ethynyl-1,1'-biphenyl (A3) 1H-NMR (CDCl3) δ: 7.96 (2H, dd, J = 8.5, 5.3 Hz), 7.79 (1H, d, J = 5.0 Hz), 7.69 (2H, dd, J = 8.2, 5.0 Hz), 7.57 (3H, tt, J = 11.9, 4.7 Hz), 7.40 (2H, tt, J = 13.1, 4.7 Hz), 7.11 (1H, dd, J = 7.8, 5.0 Hz), 4.37 (1H, s), 4.06 (2H, q, J = 5.6 Hz), 3.46 (2H, q, J = 5.6 Hz), 2.53 (3H, d, J = 5.0 Hz).; 13C-NMR (CDCl3) δ: 23.9, 55.6, 58.0, 88.0, 88.9, 122.6, 122.7, 124.2, 127.4, 127.4, 128.2, 128.3, 128.9, 130.3, 131.4, 131.6, 136.4, 137.8, 138.7, 141.6, 144.9, 158.5. 4'-(2-hydroxyethanesulfonyl) -3- (6-methylpyridin-2-yl) ethynyl-1,1'-biphenyl (A3) 1 H-NMR (CDCl 3 ) δ: 7.96 (2H, dd, J = 8.5) , 5.3 Hz), 7.79 (1H, d, J = 5.0 Hz), 7.69 (2H, dd, J = 8.2, 5.0 Hz), 7.57 (3H, tt, J = 11.9, 4.7 Hz), 7.40 (2H, tt) , J = 13.1, 4.7 Hz), 7.11 (1H, dd, J = 7.8, 5.0 Hz), 4.37 (1H, s), 4.06 (2H, q, J = 5.6 Hz), 3.46 (2H, q, J = 5.6 Hz), 2.53 (3H, d, J = 5.0 Hz) .; 13 C-NMR (CDCl 3 ) δ: 23.9, 55.6, 58.0, 88.0, 88.9, 122.6, 122.7, 124.2, 127.4, 127.4, 128.2, 128.3 , 128.9, 130.3, 131.4, 131.6, 136.4, 137.8, 138.7, 141.6, 144.9, 158.5.

2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(6-methylpyridin-2-yl)ethynyl-1,1'-biphenyl (A4) 1H-NMR (CDCl3) δ: 8.00 (2H, dt, J = 8.7, 1.8 Hz), 7.72 (3H, ddd, J = 12.8, 7.8, 1.8 Hz), 7.61 (2H, tt, J = 6.9, 3.3 Hz), 7.36 (1H, d, J= 7.3 Hz), 7.17 (2H, dt, J = 19.7, 6.2 Hz), 4.07 (2H, t, J = 5.7 Hz), 3.73 (1H, s), 3.46-3.43 (2H, m), 2.56 (3H, s).; 13C-NMR (CDCl3) δ: 24.2, 55.9, 58.2, 87.0, 88.9, 116.7 (d, J = 23.0 Hz), 119.1 (d, J = 3.8 Hz), 122.9, 124.3, 127.2 (d, J = 14.4 Hz), 127.7, 128.1, 129.7 (d, J = 3.8 Hz), 133.9 (d, J = 9.6 Hz), 134.2 (d, J = 3.8 Hz), 136.5, 138.3, 140.3, 141.8, 158.2, 158.8, 160.7. 2-fluoro-4'-(2-hydroxyethanesulfonyl) -5- (6-methylpyridin-2-yl) ethynyl-1,1'-biphenyl (A4) 1 H-NMR (CDCl 3 ) δ: 8.00 (2H, dt) , J = 8.7, 1.8 Hz), 7.72 (3H, ddd, J = 12.8, 7.8, 1.8 Hz), 7.61 (2H, tt, J = 6.9, 3.3 Hz), 7.36 (1H, d, J = 7.3 Hz) , 7.17 (2H, dt, J = 19.7, 6.2 Hz), 4.07 (2H, t, J = 5.7 Hz), 3.73 (1H, s), 3.46-3.43 (2H, m), 2.56 (3H, s). 13 C-NMR (CDCl 3 ) δ: 24.2, 55.9, 58.2, 87.0, 88.9, 116.7 (d, J = 23.0 Hz), 119.1 (d, J = 3.8 Hz), 122.9, 124.3, 127.2 (d, J) = 14.4 Hz), 127.7, 128.1, 129.7 (d, J = 3.8 Hz), 133.9 (d, J = 9.6 Hz), 134.2 (d, J = 3.8 Hz), 136.5, 138.3, 140.3, 141.8, 158.2, 158.8 , 160.7.

3-tert-butyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A5) 1H-NMR (CDCl3) δ: 8.65 (1H, td, J= 2.5, 0.9 Hz), 8.03-8.00 (2H, m), 7.80 (2H, dt, J = 8.7, 1.8 Hz), 7.73-7.67 (3H, m), 7.61 (1H, t, J = 1.8 Hz), 7.57 (1H, dt, J = 7.8, 1.1 Hz), 7.27 (2H, tt, J = 5.7, 1.8 Hz), 4.06 (2H, q, J = 5.6 Hz), 3.42-3.40 (2H, m), 2.83 (1H, t, J = 6.2 Hz), 1.40 (9H, s).; 13C-NMR (CDCl3) δ: 31.2, 34.9, 56.4, 58.4, 88.7, 89.1, 122.8, 122.9, 125.3, 127.1, 127.9, 128.2, 128.6, 129.4, 129.6, 134.0, 136.3, 137.7, 139.1, 143.2, 146.6, 150.1, 152.4. 3-tert-butyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A5) 1 H-NMR (CDCl 3 ) δ: 8.65 (1H, td, J = 2.5, 0.9 Hz), 8.03-8.00 (2H, m), 7.80 (2H, dt, J = 8.7, 1.8 Hz), 7.73-7.67 (3H, m), 7.61 (1H, t, J = 1.8 Hz) ), 7.57 (1H, dt, J = 7.8, 1.1 Hz), 7.27 (2H, tt, J = 5.7, 1.8 Hz), 4.06 (2H, q, J = 5.6 Hz), 3.42-3.40 (2H, m) , 2.83 (1H, t, J = 6.2 Hz), 1.40 (9H, s) .; 13 C-NMR (CDCl 3 ) δ: 31.2, 34.9, 56.4, 58.4, 88.7, 89.1, 122.8, 122.9, 125.3, 127.1 , 127.9, 128.2, 128.6, 129.4, 129.6, 134.0, 136.3, 137.7, 139.1, 143.2, 146.6, 150.1, 152.4.

4'-(2-hydroxyethanesulfonyl)-3-methyl-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A6) 1H-NMR (CDCl3) δ: 8.63 (1H, dq, J= 5.0, 0.9 Hz), 8.02-7.99 (2H, m), 7.78 (2H, dd, J = 6.9, 1.8 Hz), 7.71 (1H, td, J = 7.8, 1.8 Hz), 7.66 (1H, s), 7.55 (1H, dt, J = 7.8, 1.1 Hz), 7.49 (1H, s), 7.42 (1H, s), 7.29-7.25 (1H, m), 4.06 (2H, q, J = 5.6 Hz), 3.41 (2H, td, J = 4.1, 2.0 Hz), 3.01 (1H, t, J = 6.2 Hz), 2.45 (3H, s).; 13C-NMR (CDCl3) δ: 21.3, 56.4, 58.4, 88.7, 88.9, 122.9, 123.0, 127.2, 128.0, 128.2, 128.4, 128.6, 128.8, 132.1, 132.7, 136.3, 137.7, 139.1, 139.2, 143.2, 146.1, 150.1. 4'-(2-hydroxyethanesulfonyl) -3-methyl-5-(pyridin-2-ylethynyl) -1,1'-biphenyl (A6) 1 H-NMR (CDCl 3 ) δ: 8.63 (1H, dq, J = 5.0, 0.9 Hz), 8.02-7.99 (2H, m), 7.78 (2H, dd, J = 6.9, 1.8 Hz), 7.71 (1H, td, J = 7.8, 1.8 Hz), 7.66 (1H, s), 7.55 (1H, dt, J = 7.8, 1.1 Hz), 7.49 (1H, s), 7.42 (1H, s), 7.29-7.25 (1H, m), 4.06 (2H, q, J = 5.6 Hz), 3.41 (2H, td, J = 4.1, 2.0 Hz), 3.01 (1H, t, J = 6.2 Hz), 2.45 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 21.3, 56.4, 58.4, 88.7 , 88.9, 122.9, 123.0, 127.2, 128.0, 128.2, 128.4, 128.6, 128.8, 132.1, 132.7, 136.3, 137.7, 139.1, 139.2, 143.2, 146.1, 150.1.

4'-(2-hydroxyethanesulfonyl)-3-(pyridin-2-ylethynyl)-5-trifluoromethyl-1,1'-biphenyl (A7) 1H-NMR (CDCl3) δ: 8.67-8.66 (1H, m), 8.06 (2H, dt, J = 8.5, 2.1 Hz), 8.03 (1H, s), 7.93 (1H, s), 7.82 (3H, dt, J = 8.7, 1.8 Hz), 7.74 (1H, td, J = 7.6, 1.7 Hz), 7.58 (1H, dt, J = 7.8, 1.1 Hz), 7.32 (1H, ddd, J = 7.7, 4.9, 1.3 Hz), 4.07 (2H, dd, J = 10.5, 6.4 Hz), 3.42 (2H, td, J = 4.1, 2.0 Hz), 2.79 (1H, t, J = 6.2 Hz).; 13C-NMR (CDCl3) δ: 56.4, 58.4, 86.7, 90.7, 122.0, 123.5, 124.4 (d, J = 2.9 Hz), 124.7, 127.4, 128.2, 128.8 (d, J= 3.8 Hz), 128.9, 131.9, 132.3, 133.9, 136.4, 138.8, 140.2, 142.5, 144.5, 150.3.; 19F-NMR (CDCl3) δ: 37.2. 4'-(2-hydroxyethanesulfonyl) -3- (pyridin-2-ylethynyl) -5-trifluoromethyl-1,1'-biphenyl (A7) 1 H-NMR (CDCl 3 ) δ: 8.67-8.66 (1H, m) , 8.06 (2H, dt, J = 8.5, 2.1 Hz), 8.03 (1H, s), 7.93 (1H, s), 7.82 (3H, dt, J = 8.7, 1.8 Hz), 7.74 (1H, td, J) = 7.6, 1.7 Hz), 7.58 (1H, dt, J = 7.8, 1.1 Hz), 7.32 (1H, ddd, J = 7.7, 4.9, 1.3 Hz), 4.07 (2H, dd, J = 10.5, 6.4 Hz) , 3.42 (2H, td, J = 4.1, 2.0 Hz), 2.79 (1H, t, J = 6.2 Hz).; 13 C-NMR (CDCl 3 ) δ: 56.4, 58.4, 86.7, 90.7, 122.0, 123.5, 124.4 (d, J = 2.9 Hz), 124.7, 127.4, 128.2, 128.8 (d, J = 3.8 Hz), 128.9, 131.9, 132.3, 133.9, 136.4, 138.8, 140.2, 142.5, 144.5, 150.3.; 19 F- NMR (CDCl 3 ) δ: 37.2.

4'-(2-hydroxyethanesulfonyl)-4-methyl-3-(pyridin-2-ylethynyl)-1,1'-biphenyl (A8) 1H-NMR (CDCl3) δ: 8.66 (1H, dq, J= 5.0, 0.9 Hz), 8.00 (2H, dt, J = 8.5, 2.1 Hz), 7.85 (1H, d, J = 1.8 Hz), 7.79 (2H, dt, J = 8.7, 1.8 Hz), 7.72 (1H, td, J = 7.8, 1.8 Hz), 7.55 (2H, ddd, J = 13.5, 7.8, 1.6 Hz), 7.38 (1H, d, J = 7.8 Hz), 7.28 (1H, dt, J = 5.5, 1.9 Hz), 4.05 (2H, dd, J = 10.5, 6.4 Hz), 3.40 (2H, t, J = 5.3 Hz), 2.80 (1H, t, J = 6.4 Hz), 2.62 (3H, s).; 13C-NMR (CDCl3) δ: 20.5, 56.3, 58.4, 87.5, 93.0, 122.9, 123.0, 127.2, 127.7, 127.8, 128.6, 130.4, 131.1, 132.0, 132.1, 136.2, 136.4, 137.5, 141.4, 143.3, 145.9, 150.1. 4'-(2-hydroxyethanesulfonyl) -4-methyl-3- (pyridin-2-ylethynyl) -1,1'-biphenyl (A8) 1 H-NMR (CDCl 3 ) δ: 8.66 (1H, dq, J = 5.0, 0.9 Hz), 8.00 (2H, dt, J = 8.5, 2.1 Hz), 7.85 (1H, d, J = 1.8 Hz), 7.79 (2H, dt, J = 8.7, 1.8 Hz), 7.72 (1H, 1H, td, J = 7.8, 1.8 Hz), 7.55 (2H, ddd, J = 13.5, 7.8, 1.6 Hz), 7.38 (1H, d, J = 7.8 Hz), 7.28 (1H, dt, J = 5.5, 1.9 Hz) ), 4.05 (2H, dd, J = 10.5, 6.4 Hz), 3.40 (2H, t, J = 5.3 Hz), 2.80 (1H, t, J = 6.4 Hz), 2.62 (3H, s) .; 13 C -NMR (CDCl 3 ) δ: 20.5, 56.3, 58.4, 87.5, 93.0, 122.9, 123.0, 127.2, 127.7, 127.8, 128.6, 130.4, 131.1, 132.0, 132.1, 136.2, 136.4, 137.5, 141.4, 143.3, 145.9, 150.1.

4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl)ethynyl-1,1'-biphenyl (A9) 1H-NMR (CDCl3) δ: 8.46 (1H, d, J = 5.0 Hz), 8.01 (2H, d, J = 8.7 Hz), 7.84 (1H, s), 7.78 (2H, t, J = 4.1 Hz), 7.67-7.44 (6H, m), 7.19 (1H, dd, J = 7.6, 4.8 Hz), 4.05 (2H, s), 3.42 (2H, t, J = 5.7 Hz), 3.31 (1H, s), 2.55 (3H, s).; 13C-NMR (CDCl3) δ: 19.5, 56.3,58.4, 88.1, 92.3, 123.0, 123.5, 127.9, 128.0, 128.5, 128.6, 128.7, 129.3, 130.8, 132.0, 136.1, 137.2, 138.0, 139.3, 142.7, 145.9, 147.4. 4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl) ethynyl-1,1'-biphenyl (A9) 1 H-NMR (CDCl 3 ) δ: 8.46 (1H, d, J = 5.0) Hz), 8.01 (2H, d, J = 8.7 Hz), 7.84 (1H, s), 7.78 (2H, t, J = 4.1 Hz), 7.67-7.44 (6H, m), 7.19 (1H, dd, J) = 7.6, 4.8 Hz), 4.05 (2H, s), 3.42 (2H, t, J = 5.7 Hz), 3.31 (1H, s), 2.55 (3H, s).; 13 C-NMR (CDCl 3 ) δ : 19.5, 56.3,58.4, 88.1, 92.3, 123.0, 123.5, 127.9, 128.0, 128.5, 128.6, 128.7, 129.3, 130.8, 132.0, 136.1, 137.2, 138.0, 139.3, 142.7, 145.9, 147.4.

4'-(2-hydroxyethanesulfonyl)-3-(6-methylpyridin-2-yl)ethynyl-4-methyl-1,1'-biphenyl (A10) 1H-NMR (CDCl3) δ: 7.96 (2H, d, J = 8.7 Hz), 7.82 (1H, s), 7.73 (2H, d, J= 8.7 Hz), 7.59 (1H, dd, J = 9.2, 6.0 Hz), 7.49 (1H, dd, J = 8.0, 1.6 Hz), 7.36 (2H, dd, J = 18.3, 7.8 Hz), 7.13 (1H, d, J = 7.3 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.49 (1H, br s), 3.41 (2H, t, J = 5.7 Hz), 2.58 (6H, s).; 13C-NMR (CDCl3) δ: 20.4, 24.4, 56.1, 58.3, 87.1, 93.1, 122.8, 123.0, 124.4, 127.6, 128.5, 130.3, 131.0, 136.3, 136.4, 137.5, 141.2, 142.4, 145.6, 158.9. 4'-(2-hydroxyethanesulfonyl) -3- (6-methylpyridin-2-yl) ethynyl-4-methyl-1,1'-biphenyl (A10) 1 H-NMR (CDCl 3 ) δ: 7.96 (2H, d) , J = 8.7 Hz), 7.82 (1H, s), 7.73 (2H, d, J = 8.7 Hz), 7.59 (1H, dd, J = 9.2, 6.0 Hz), 7.49 (1H, dd, J = 8.0, 1.6 Hz), 7.36 (2H, dd, J = 18.3, 7.8 Hz), 7.13 (1H, d, J = 7.3 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.49 (1H, br s), 3.41 (2H, t, J = 5.7 Hz), 2.58 (6H, s) .; 13 C-NMR (CDCl 3 ) δ: 20.4, 24.4, 56.1, 58.3, 87.1, 93.1, 122.8, 123.0, 124.4, 127.6, 128.5, 130.3, 131.0, 136.3, 136.4, 137.5, 141.2, 142.4, 145.6, 158.9.

4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl)ethynyl-4-methyl-1,1'-biphenyl (A11) 1H-NMR (CDCl3) δ: 8.49 (1H, dd, J = 4.8, 1.1 Hz), 8.00 (2H, dt, J = 8.7, 1.8 Hz), 7.87 (1H, d, J = 2.3 Hz), 7.80-7.77 (2H, m), 7.58 (1H, dt, J = 7.8, 0.9 Hz), 7.53 (1H, dd, J = 7.8, 1.8 Hz), 7.38 (1H, d, J= 7.8 Hz), 7.20 (1H, dd, J = 7.8, 4.6 Hz), 4.05 (2H, s), 3.42-3.39 (2H, m), 2.93 (1H, s), 2.62 (3H, s), 2.56 (3H, s).; 13C-NMR (CDCl3) δ: 19.7, 20.7, 56.4, 58.4, 91.2, 92.0, 122.9, 123.4, 127.7, 127.8, 128.6, 130.4, 131.3, 135.9, 136.5, 137.1, 137.5, 141.2, 143.0, 145.9, 147.5. 4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl) ethynyl-4-methyl-1,1'-biphenyl (A11) 1 H-NMR (CDCl 3 ) δ: 8.49 (1H, dd) , J = 4.8, 1.1 Hz), 8.00 (2H, dt, J = 8.7, 1.8 Hz), 7.87 (1H, d, J = 2.3 Hz), 7.80-7.77 (2H, m), 7.58 (1H, dt, J = 7.8, 0.9 Hz), 7.53 (1H, dd, J = 7.8, 1.8 Hz), 7.38 (1H, d, J = 7.8 Hz), 7.20 (1H, dd, J = 7.8, 4.6 Hz), 4.05 ( 2H, s), 3.42-3.39 (2H, m), 2.93 (1H, s), 2.62 (3H, s), 2.56 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 19.7, 20.7, 56.4, 58.4, 91.2, 92.0, 122.9, 123.4, 127.7, 127.8, 128.6, 130.4, 131.3, 135.9, 136.5, 137.1, 137.5, 141.2, 143.0, 145.9, 147.5.

4'-(2-hydroxyethanesulfonyl)-2-methyl-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A12) 1H-NMR (CDCl3) δ: 8.61 (1H, dq, J= 5.0, 0.9 Hz), 7.99 (2H, dt, J = 8.4, 1.9 Hz), 7.69 (1H, td, J = 7.7, 1.7 Hz), 7.56-7.50 (4H, m), 7.47 (1H, d, J = 1.8 Hz), 7.31 (1H, d, J= 7.8 Hz), 7.25 (1H, tt, J = 6.4, 1.7 Hz), 4.07 (2H, q, J = 5.6 Hz), 3.44 (2H, td, J = 4.1, 2.1 Hz), 3.12 (1H, s), 2.27 (3H, s).; 13C-NMR (CDCl3) δ: 20.4, 56.3, 58.3, 88.7, 88.7, 120.1, 122.8, 127.1, 128.4, 130.2, 130.9, 131.7, 132.1, 132.9, 136.2, 136.4, 137.7, 139.9, 143.2, 146.9, 150.0. 4'-(2-hydroxyethanesulfonyl) -2-methyl-5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A12) 1 H-NMR (CDCl 3 ) δ: 8.61 (1H, dq, J = 5.0, 0.9 Hz), 7.99 (2H, dt, J = 8.4, 1.9 Hz), 7.69 (1H, td, J = 7.7, 1.7 Hz), 7.56-7.50 (4H, m), 7.47 (1H, d, J) = 1.8 Hz), 7.31 (1H, d, J = 7.8 Hz), 7.25 (1H, tt, J = 6.4, 1.7 Hz), 4.07 (2H, q, J = 5.6 Hz), 3.44 (2H, td, J) = 4.1, 2.1 Hz), 3.12 (1H, s), 2.27 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 20.4, 56.3, 58.3, 88.7, 88.7, 120.1, 122.8, 127.1, 128.4, 130.2, 130.9, 131.7, 132.1, 132.9, 136.2, 136.4, 137.7, 139.9, 143.2, 146.9, 150.0.

4'-(2-hydroxyethanesulfonyl)-4-propyl-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A14) 1H-NMR (CDCl3) δ: 8.64 (1H, dq, J= 4.9, 0.9 Hz), 8.00-7.97 (2H, m), 7.85 (1H, d, J = 1.8 Hz), 7.79-7.77 (2H, m), 7.72 (1H, td, J = 7.8, 1.8 Hz), 7.54 (2H, dd, J = 7.8, 1.2 Hz), 7.36 (1H, d, J = 7.9 Hz), 7.28 (1H, ddd, J = 7.6, 5.0, 1.1 Hz), 4.05 (2H, dd, J = 11.0, 5.9 Hz), 3.43-3.40 (2H, m), 3.15 (1H, s), 2.92 (2H, t, J = 7.6 Hz), 1.79 (2H, td, J = 14.9, 7.4 Hz), 1.03 (3H, t, J = 7.4 Hz).; 13C-NMR (CDCl3) δ: 13.9, 23.7, 36.3, 56.3, 58.3, 87.5, 92.4, 122.6, 122.9, 127.2, 127.7, 128.6, 129.7, 131.5, 136.3, 136.4, 137.5, 143.3, 145.8, 145.8, 150.1. 4'-(2-hydroxyethanesulfonyl) -4-propyl-5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A14) 1 H-NMR (CDCl 3 ) δ: 8.64 (1H, dq, J = 4.9, 0.9 Hz), 8.00-7.97 (2H, m), 7.85 (1H, d, J = 1.8 Hz), 7.79-7.77 (2H, m), 7.72 (1H, td, J = 7.8, 1.8 Hz), 7.54 (2H, dd, J = 7.8, 1.2 Hz), 7.36 (1H, d, J = 7.9 Hz), 7.28 (1H, ddd, J = 7.6, 5.0, 1.1 Hz), 4.05 (2H, dd, J = 11.0, 5.9 Hz), 3.43-3.40 (2H, m), 3.15 (1H, s), 2.92 (2H, t, J = 7.6 Hz), 1.79 (2H, td, J = 14.9, 7.4 Hz), 1.03 ( 3H, t, J = 7.4 Hz) .; 13 C-NMR (CDCl 3 ) δ: 13.9, 23.7, 36.3, 56.3, 58.3, 87.5, 92.4, 122.6, 122.9, 127.2, 127.7, 128.6, 129.7, 131.5, 136.3 , 136.4, 137.5, 143.3, 145.8, 145.8, 150.1.

4'-(2-hydroxyethanesulfonyl)-4-pentyl-3-(pyridin-2-ylethynyl)-1,1'-biphenyl (A16) 1H-NMR (CDCl3) δ: 8.65 (1H, d, J = 4.1 Hz), 7.99 (2H, d, J = 8.7 Hz), 7.86 (1H, d, J= 1.8 Hz), 7.79 (2H, d, J = 8.2 Hz), 7.71 (1H, td, J = 7.8, 1.8 Hz), 7.54 (2H, td, J = 5.3, 2.7 Hz), 7.37 (1H, d, J = 7.8 Hz), 7.27 (1H, ddd, J = 7.7, 4.9, 1.3 Hz), 4.05 (2H, dd, J = 11.0, 6.4 Hz), 3.40 (2H, dd, J = 7.1, 3.9 Hz), 2.94 (2H, t, J = 7.8 Hz), 2.89 (1H, t, J = 6.4 Hz), 1.75 (2H, dd, J = 15.1, 7.3 Hz), 1.43-1.38 (4H, m), 0.90 (3H, t, J = 7.1 Hz).; 13C-NMR (CDCl3) δ: 14.0, 22.5, 30.3, 31.6, 34.3, 56.4, 58.4, 87.5, 92.5, 122.6, 122.9, 127.2, 127.8, 127.8, 128.6, 129.7, 131.6, 136.2, 136.4, 137.5, 143.4, 145.9, 146.2, 150.2. 4'-(2-hydroxyethanesulfonyl) -4-pentyl-3- (pyridin-2-ylethynyl) -1,1'-biphenyl (A16) 1 H-NMR (CDCl 3 ) δ: 8.65 (1H, d, J = 4.1 Hz), 7.99 (2H, d, J = 8.7 Hz), 7.86 (1H, d, J = 1.8 Hz), 7.79 (2H, d, J = 8.2 Hz), 7.71 (1H, td, J = 7.8, 1.8 Hz), 7.54 (2H, td, J = 5.3, 2.7 Hz), 7.37 (1H, d, J = 7.8 Hz), 7.27 (1H, ddd, J = 7.7, 4.9, 1.3 Hz), 4.05 (2H, dd, J = 11.0, 6.4 Hz), 3.40 (2H, dd, J = 7.1, 3.9 Hz), 2.94 (2H, t, J = 7.8 Hz), 2.89 (1H, t, J = 6.4 Hz), 1.75 ( 2H, dd, J = 15.1, 7.3 Hz), 1.43-1.38 (4H, m), 0.90 (3H, t, J = 7.1 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 22.5, 30.3, 31.6, 34.3, 56.4, 58.4, 87.5, 92.5, 122.6, 122.9, 127.2, 127.8, 127.8, 128.6, 129.7, 131.6, 136.2, 136.4, 137.5, 143.4, 145.9, 146.2, 150.2.

4'-(2-hydroxyethanesulfonyl)-4-iso-propyl-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A17) 1H-NMR (CDCl3) δ: 8.66 (1H, d, J= 5.0 Hz), 8.00 (2H, t, J = 4.4 Hz), 7.86 (1H, d, J = 1.8 Hz), 7.79 (2H, t, J = 4.4 Hz), 7.71 (1H, td, J = 7.8, 1.8 Hz), 7.59 (1H, dd, J = 8.0, 2.1 Hz), 7.56 (1H, d, J = 7.8 Hz), 7.44 (1H, d, J = 8.2 Hz), 7.27 (1H, tt, J = 5.7, 1.7 Hz), 4.05 (2H, q, J= 5.6 Hz), 3.64 (1H, t, J = 6.9 Hz), 3.41 (2H, td, J = 4.2, 2.1 Hz), 2.90 (1H, s), 1.36 (6H, d, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 23.1, 31.6, 56.4, 58.4, 87.4, 92.8, 122.0, 122.9, 126.1, 127.3, 127.8, 128.2, 128.6, 131.7, 136.2, 136.4, 137.5, 143.4, 146.0, 150.2, 151.7. 4'-(2-hydroxyethanesulfonyl) -4-iso-propyl-5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A17) 1 H-NMR (CDCl 3 ) δ: 8.66 (1H, d, J = 5.0 Hz), 8.00 (2H, t, J = 4.4 Hz), 7.86 (1H, d, J = 1.8 Hz), 7.79 (2H, t, J = 4.4 Hz), 7.71 (1H, td, J = 7.8, 1.8 Hz), 7.59 (1H, dd, J = 8.0, 2.1 Hz), 7.56 (1H, d, J = 7.8 Hz), 7.44 (1H, d, J = 8.2 Hz), 7.27 (1H, tt, J = 5.7, 1.7 Hz), 4.05 (2H, q, J = 5.6 Hz), 3.64 (1H, t, J = 6.9 Hz), 3.41 (2H, td, J = 4.2, 2.1 Hz), 2.90 (1H, 1H, s), 1.36 (6H, d, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 23.1, 31.6, 56.4, 58.4, 87.4, 92.8, 122.0, 122.9, 126.1, 127.3, 127.8, 128.2, 128.6, 131.7, 136.2, 136.4, 137.5, 143.4, 146.0, 150.2, 151.7.

4-iso-butyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A18) 1H-NMR (CDCl3) δ: 8.64 (1H, d, J= 4.6 Hz), 7.99 (2H, d, J = 8.2 Hz), 7.87 (1H, d, J = 1.8 Hz), 7.79 (2H, d, J = 8.2 Hz), 7.71 (1H, td, J = 7.7, 1.7 Hz), 7.54 (2H, dt, J = 7.8, 2.1 Hz), 7.32 (1H, d, J = 8.2 Hz), 7.27 (1H, dd, J = 8.0, 4.4 Hz), 4.05 (2H, q, J = 5.5 Hz), 3.41 (2H, t, J= 5.5 Hz), 2.98 (1H, t, J = 6.2 Hz), 2.82 (2H, d, J = 6.9 Hz), 2.15-2.09 (1H, m), 1.01 (6H, d, J = 6.4 Hz).; 13C-NMR (CDCl3) δ: 22.5, 29.9, 43.6, 56.4, 58.4, 87.9, 92.6, 122.9, 123.0, 127.1, 127.5, 127.4, 128.6, 130.6, 131.5, 136.2, 136.5, 137.5, 143.4, 145.1, 145.9, 150.2. 4-iso-butyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A18) 1 H-NMR (CDCl 3 ) δ: 8.64 (1H, d, J = 4.6 Hz), 7.99 (2H, d, J = 8.2 Hz), 7.87 (1H, d, J = 1.8 Hz), 7.79 (2H, d, J = 8.2 Hz), 7.71 (1H, td, J = 7.7, 1.7 Hz), 7.54 (2H, dt, J = 7.8, 2.1 Hz), 7.32 (1H, d, J = 8.2 Hz), 7.27 (1H, dd, J = 8.0, 4.4 Hz), 4.05 (2H, q, J = 5.5 Hz), 3.41 (2H, t, J = 5.5 Hz), 2.98 (1H, t, J = 6.2 Hz), 2.82 (2H, d, J = 6.9 Hz), 2.15-2.09 (1H, m), 1.01 (6H, d, J = 6.4 Hz) .; 13 C-NMR (CDCl 3 ) δ: 22.5, 29.9, 43.6, 56.4, 58.4, 87.9, 92.6, 122.9, 123.0, 127.1, 127.5, 127.4, 128.6, 130.6, 131.5, 136.2, 136.5, 137.5, 143.4, 145.1, 145.9, 150.2.

4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl)ethynyl-4-propyl-1,1'-biphenyl (A19) 1H-NMR (CDCl3) δ: 8.48 (1H, dd, J = 4.7, 0.9 Hz), 7.99 (2H, dt, J = 8.7, 2.0 Hz), 7.89 (1H, d, J = 1.9 Hz), 7.79 (2H, dt, J = 8.7, 2.0 Hz), 7.56 (2H, ddt, J = 11.8, 7.2, 2.5 Hz), 7.37 (1H, d, J = 8.0 Hz), 7.19 (1H, dd, J = 7.8, 4.7 Hz), 4.05 (2H, dt, J = 5.9, 2.4 Hz), 3.42-3.40 (2H, m), 2.94 (3H, t, J = 7.7 Hz), 2.56 (3H, s), 1.79 (2H, td, J = 15.0, 7.5 Hz), 1.02 (3H, t, J = 7.3 Hz).; 13C-NMR (CDCl3) δ: 14.0, 19.6, 23.8, 36.5, 56.4, 58.4, 91.2, 91.4, 122.8, 122.9, 127.7, 127.8, 128.6, 129.7, 131.7, 135.8, 136.5, 137.1, 137.5, 143.0, 145.6, 145.9, 147.5. 4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl) ethynyl-4-propyl-1,1'-biphenyl (A19) 1 H-NMR (CDCl 3 ) δ: 8.48 (1H, dd) , J = 4.7, 0.9 Hz), 7.99 (2H, dt, J = 8.7, 2.0 Hz), 7.89 (1H, d, J = 1.9 Hz), 7.79 (2H, dt, J = 8.7, 2.0 Hz), 7.56 (2H, ddt, J = 11.8, 7.2, 2.5 Hz), 7.37 (1H, d, J = 8.0 Hz), 7.19 (1H, dd, J = 7.8, 4.7 Hz), 4.05 (2H, dt, J = 5.9) , 2.4 Hz), 3.42-3.40 (2H, m), 2.94 (3H, t, J = 7.7 Hz), 2.56 (3H, s), 1.79 (2H, td, J = 15.0, 7.5 Hz), 1.02 (3H) , t, J = 7.3 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 19.6, 23.8, 36.5, 56.4, 58.4, 91.2, 91.4, 122.8, 122.9, 127.7, 127.8, 128.6, 129.7, 131.7, 135.8, 136.5, 137.1, 137.5, 143.0, 145.6, 145.9, 147.5.

4'-(2-hydroxyethanesulfonyl)-3-(3-penthylpyridin-2-yl)ethynyl-4-propyl-1,1'-biphenyl (A21) 1H-NMR (CDCl3) δ: 8.49 (1H, t, J = 2.4 Hz), 8.00 (2H, d, J = 8.3 Hz), 7.89 (1H, d, J = 1.7 Hz), 7.79 (2H, t, J = 4.1 Hz), 7.56 (2H, td, J = 8.0, 1.7 Hz), 7.37 (1H, d, J = 8.0 Hz), 7.21 (1H, dd, J= 7.8, 4.7 Hz), 4.05 (2H, dd, J = 10.8, 6.3 Hz), 3.41 (2H, td, J= 4.2, 2.1 Hz), 2.92 (5H, dt, J = 19.2, 7.7 Hz), 1.77 (4H, tt, J= 21.5, 7.1 Hz), 1.40-1.36 (4H, m), 1.02 (3H, t, J = 7.3 Hz), 0.89 (3H, t, J = 7.0 Hz).; 13C-NMR (CDCl3) δ: 13.9, 14.0, 22.6, 23.8, 30.0, 31.6, 33.3, 36.3, 56.4, 58.4, 90.4, 91.5, 122.9, 123.1, 127.7, 127.8, 128.6, 129.7, 131.8, 136.4, 136.5, 137.5, 140.4, 142.6, 145.5, 146.0, 147.6. 4'-(2-hydroxyethanesulfonyl) -3- (3-penthylpyridin-2-yl) ethynyl-4-propyl-1,1'-biphenyl (A21) 1 H-NMR (CDCl 3 ) δ: 8.49 (1H, t) , J = 2.4 Hz), 8.00 (2H, d, J = 8.3 Hz), 7.89 (1H, d, J = 1.7 Hz), 7.79 (2H, t, J = 4.1 Hz), 7.56 (2H, td, J) = 8.0, 1.7 Hz), 7.37 (1H, d, J = 8.0 Hz), 7.21 (1H, dd, J = 7.8, 4.7 Hz), 4.05 (2H, dd, J = 10.8, 6.3 Hz), 3.41 (2H) , td, J = 4.2, 2.1 Hz), 2.92 (5H, dt, J = 19.2, 7.7 Hz), 1.77 (4H, tt, J = 21.5, 7.1 Hz), 1.40-1.36 (4H, m), 1.02 ( 3H, t, J = 7.3 Hz), 0.89 (3H, t, J = 7.0 Hz) .; 13 C-NMR (CDCl 3 ) δ: 13.9, 14.0, 22.6, 23.8, 30.0, 31.6, 33.3, 36.3, 56.4 , 58.4, 90.4, 91.5, 122.9, 123.1, 127.7, 127.8, 128.6, 129.7, 131.8, 136.4, 136.5, 137.5, 140.4, 142.6, 145.5, 146.0, 147.6.

4-heptyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A22) 1H-NMR (CDCl3) δ: 8.66-8.64 (1H, m), 7.99 (2H, dd, J = 6.4, 1.8 Hz), 7.86 (1H, d, J = 1.8 Hz), 7.79 (2H, dt, J = 8.7, 1.8 Hz), 7.72 (1H, td, J = 7.8, 1.8 Hz), 7.54 (2H, dt, J = 7.9, 1.7 Hz), 7.36 (1H, d, J = 7.8 Hz), 7.28 (1H, tt, J = 5.7, 1.8 Hz), 4.05 (2H, q, J = 5.6 Hz), 3.42-3.40 (2H, m), 2.99-2.92 (3H, m), 1.78-1.71 (2H, m), 1.38 (4H, tt, J = 18.8, 5.2 Hz), 1.28 (4H, dt, J = 11.3, 4.4 Hz), 0.86 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 14.1, 22.6, 29.1, 29.4, 30.6, 31.8, 34.4, 56.4, 58.3, 87.5, 92.5, 122.6, 122.9, 127.2, 127.8, 127.9, 128.6, 129.7, 131.5, 136.2, 136.4, 137.4, 143.3, 145.9, 146.2, 150.1. 4-heptyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A22) 1 H-NMR (CDCl 3 ) δ: 8.66-8.64 (1H, m) , 7.99 (2H, dd, J = 6.4, 1.8 Hz), 7.86 (1H, d, J = 1.8 Hz), 7.79 (2H, dt, J = 8.7, 1.8 Hz), 7.72 (1H, td, J = 7.8) , 1.8 Hz), 7.54 (2H, dt, J = 7.9, 1.7 Hz), 7.36 (1H, d, J = 7.8 Hz), 7.28 (1H, tt, J = 5.7, 1.8 Hz), 4.05 (2H, q) , J = 5.6 Hz), 3.42-3.40 (2H, m), 2.99-2.92 (3H, m), 1.78-1.71 (2H, m), 1.38 (4H, tt, J = 18.8, 5.2 Hz), 1.28 ( 4H, dt, J = 11.3, 4.4 Hz), 0.86 (3H, t, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.1, 22.6, 29.1, 29.4, 30.6, 31.8, 34.4, 56.4 , 58.3, 87.5, 92.5, 122.6, 122.9, 127.2, 127.8, 127.9, 128.6, 129.7, 131.5, 136.2, 136.4, 137.4, 143.3, 145.9, 146.2, 150.1.

4'-(2-hydroxyethanesulfonyl)-4-octyl-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A23) 1H-NMR (CDCl3) δ: 8.65 (1H, d, J= 5.0 Hz), 8.00 (2H, d, J = 8.7 Hz), 7.86 (1H, d, J = 1.8 Hz), 7.79 (2H, d, J = 8.2 Hz), 7.71 (1H, td, J = 7.8, 1.8 Hz), 7.56-7.53 (2H, m), 7.37 (1H, d, J = 7.8 Hz), 7.29-7.27 (2H, m), 4.05 (2H, q, J = 5.6 Hz), 3.41 (2H, t, J = 5.3 Hz), 2.96-2.90 (3H, m), 1.78-1.70 (2H, m), 1.35 (10H, dq, J = 44.9, 10.4 Hz), 0.86 (3H, t, J= 6.9 Hz).; 13C-NMR (CDCl3) δ: 14.1, 22.6, 29.3, 29.4, 30.6, 31.9, 34.4, 56.4, 58.3, 87.5, 92.5, 122.6, 122.9, 127.2, 127.8, 127.8, 128.6, 129.7, 131.5, 136.2, 136.4, 137.4, 143.4, 145.9, 146.2, 150.2. 4'-(2-hydroxyethanesulfonyl) -4-octyl-5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A23) 1 H-NMR (CDCl 3 ) δ: 8.65 (1H, d, J = 5.0 Hz), 8.00 (2H, d, J = 8.7 Hz), 7.86 (1H, d, J = 1.8 Hz), 7.79 (2H, d, J = 8.2 Hz), 7.71 (1H, td, J = 7.8, 1.8 Hz), 7.56-7.53 (2H, m), 7.37 (1H, d, J = 7.8 Hz), 7.29-7.27 (2H, m), 4.05 (2H, q, J = 5.6 Hz), 3.41 (2H, t, J = 5.3 Hz), 2.96-2.90 (3H, m), 1.78-1.70 (2H, m), 1.35 (10H, dq, J = 44.9, 10.4 Hz), 0.86 (3H, t, J = 6.9 Hz) ) .; 13 C-NMR (CDCl 3 ) δ: 14.1, 22.6, 29.3, 29.4, 30.6, 31.9, 34.4, 56.4, 58.3, 87.5, 92.5, 122.6, 122.9, 127.2, 127.8, 127.8, 128.6, 129.7, 131.5 , 136.2, 136.4, 137.4, 143.4, 145.9, 146.2, 150.2.

4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A24) 1H-NMR (CDCl3) δ: 8.62 (1H, dd, J= 5.0, 0.9 Hz), 7.99 (2H, t, J = 4.4 Hz), 7.93 (1H, d, J = 16.0 Hz), 7.89 (1H, d, J = 1.8 Hz), 7.81 (2H, dd, J = 8.7, 1.8 Hz), 7.69 (1H, td, J = 7.6, 1.8 Hz), 7.46 (2H, td, J = 10.1, 4.0 Hz), 7.31 (1H, d, J = 7.8 Hz), 7.20-7.14 (2H, m), 4.04 (2H, d, J = 3.7 Hz), 3.40 (2H, td, J = 6.5, 4.1 Hz), 3.27 (1H, s), 2.84 (2H, t, J= 7.8 Hz), 1.69-1.61 (2H, m), 1.44-1.26 (10H, m), 0.86 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 26.1, 26.9, 33.4, 42.1, 56.3, 58.3, 87.5, 92.7, 122.1, 122.9, 126.5, 127.2, 127.7, 128.1, 128.6, 131.6, 136.2, 136.3, 137.4, 143.3, 145.8, 150.1, 150.7. 4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A24) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, dd, J = 5.0, 0.9 Hz), 7.99 (2H, t, J = 4.4 Hz), 7.93 (1H, d, J = 16.0 Hz), 7.89 (1H, d, J = 1.8 Hz), 7.81 (2H, dd, J = 8.7, 1.8 Hz), 7.69 (1H, td, J = 7.6, 1.8 Hz), 7.46 (2H, td, J = 10.1, 4.0 Hz), 7.31 (1H, d, J = 7.8 Hz), 7.20- 7.14 (2H, m), 4.04 (2H, d, J = 3.7 Hz), 3.40 (2H, td, J = 6.5, 4.1 Hz), 3.27 (1H, s), 2.84 (2H, t, J = 7.8 Hz) ), 1.69-1.61 (2H, m), 1.44-1.26 (10H, m), 0.86 (3H, t, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 26.1, 26.9, 33.4, 42.1 , 56.3, 58.3, 87.5, 92.7, 122.1, 122.9, 126.5, 127.2, 127.7, 128.1, 128.6, 131.6, 136.2, 136.3, 137.4, 143.3, 145.8, 150.1, 150.7.

4'-(2-hydroxyethanesulfonyl)-4-cyclo-pentyl-5-(pyridin-2-ylethynyl)-1,1'-biphenyl (A25) 1H-NMR (CDCl3) δ: 8.65 (1H, d, J= 5.0 Hz), 7.99 (2H, d, J = 8.2 Hz), 7.85 (1H, d, J = 1.8 Hz), 7.78 (2H, d, J = 8.7 Hz), 7.72 (1H, td, J = 7.8, 1.8 Hz), 7.58-7.54 (2H, m), 7.44 (1H, d, J = 8.2 Hz), 7.28 (1H, dt, J = 6.4, 2.6 Hz), 4.05 (2H, d, J = 5.0 Hz), 3.67 (1H, t, J = 8.2 Hz), 3.41 (2H, t, J = 5.5 Hz), 3.05 (1H, s), 2.20 (2H, s), 1.87-1.70 (6H, m).; 13C-NMR (CDCl3) δ: 25.8, 34.0, 43.5, 56.3, 58.3, 87.8, 92.7, 122.5, 122.9, 126.6, 127.2, 127.7, 128.0, 128.6, 131.7, 136.2, 136.3, 137.4, 143.4, 145.8, 149.7, 150.1. 4'-(2-hydroxyethanesulfonyl) -4-cyclo-pentyl-5- (pyridin-2-ylethynyl) -1,1'-biphenyl (A25) 1 H-NMR (CDCl 3 ) δ: 8.65 (1H, d, J = 5.0 Hz), 7.99 (2H, d, J = 8.2 Hz), 7.85 (1H, d, J = 1.8 Hz), 7.78 (2H, d, J = 8.7 Hz), 7.72 (1H, td, J = 7.8, 1.8 Hz), 7.58-7.54 (2H, m), 7.44 (1H, d, J = 8.2 Hz), 7.28 (1H, dt, J = 6.4, 2.6 Hz), 4.05 (2H, d, J = 5.0) Hz), 3.67 (1H, t, J = 8.2 Hz), 3.41 (2H, t, J = 5.5 Hz), 3.05 (1H, s), 2.20 (2H, s), 1.87-1.70 (6H, m). 13 C-NMR (CDCl 3 ) δ: 25.8, 34.0, 43.5, 56.3, 58.3, 87.8, 92.7, 122.5, 122.9, 126.6, 127.2, 127.7, 128.0, 128.6, 131.7, 136.2, 136.3, 137.4, 143.4, 145.8 , 149.7, 150.1.

(2)Ｂ１～Ｂ２５の合成
Ｂ１～Ｂ２５の合成は下記合成法により合成した。 (2) Synthesis of B1 to B25 The synthesis of B1 to B25 was synthesized by the following synthetic method.

Figure 0007060775000161
Figure 0007060775000161

合成したB1～B25のNMRを下記に示す。 The synthesized NMR of B1 to B25 is shown below.

4'-(2-hydroxyethanesulfonyl)-3-(pyridin-2-ylethyl)-1,1'-biphenyl (B1) 1H-NMR (CDCl3) δ: 8.55 (1H, t, J= 2.5 Hz), 7.97 (2H, t, J = 4.1 Hz), 7.71 (2H, t, J = 4.1 Hz), 7.59 (1H, td, J = 7.7, 1.8 Hz), 7.39 (3H, m), 7.27 (1H, dd, J = 7.5, 1.1 Hz), 7.15-7.10 (2H, m), 4.04 (2H, s), 3.65 (1H, s), 3.41 (2H, dd, J= 8.2, 3.2 Hz), 3.13 (4H, s).; 13C-NMR (CDCl3) δ: 35.9, 40.0, 56.1, 58.3, 121.3, 123.1, 125.0, 127.5, 127.9, 128.2, 128.4, 128.8, 129.1, 136.5, 137.3, 138.9, 142.3, 146.9, 149.1, 160.7. 4'-(2-hydroxyethanesulfonyl) -3- (pyridin-2-ylethyl) -1,1'-biphenyl (B1) 1 H-NMR (CDCl 3 ) δ: 8.55 (1H, t, J = 2.5 Hz), 7.97 (2H, t, J = 4.1 Hz), 7.71 (2H, t, J = 4.1 Hz), 7.59 (1H, td, J = 7.7, 1.8 Hz), 7.39 (3H, m), 7.27 (1H, dd) , J = 7.5, 1.1 Hz), 7.15-7.10 (2H, m), 4.04 (2H, s), 3.65 (1H, s), 3.41 (2H, dd, J = 8.2, 3.2 Hz), 3.13 (4H, s) s) .; 13 C-NMR (CDCl 3 ) δ: 35.9, 40.0, 56.1, 58.3, 121.3, 123.1, 125.0, 127.5, 127.9, 128.2, 128.4, 128.8, 129.1, 136.5, 137.3, 138.9, 142.3, 146.9, 149.1, 160.7.

2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B2) 1H-NMR (CDCl3) δ: 8.55 (1H, dq, J= 5.0, 0.9 Hz), 7.98 (2H, dt, J = 8.5, 2.1 Hz), 7.71-7.46 (4H, m), 7.21 (2H, dt, J = 8.1, 3.2 Hz), 7.15 (1H, ddd, J = 7.6, 5.0, 1.1 Hz), 7.08 (2H, ddd, J = 9.8, 7.3, 1.6 Hz), 4.05 (2H, t, J = 5.7 Hz), 3.51 (1H, s), 3.43-3.40 (2H, m), 3.10 (4H, q, J = 4.4 Hz).; 13C-NMR (CDCl3) δ: 35.0, 40.0, 56.2, 58.3, 116.2 (d, J = 23.0 Hz), 121.4, 123.1, 126.5 (d, J = 13.4 Hz), 128.0, 128.5 (d, J = 11.5 Hz), 129.9 (d, J = 2.9 Hz), 130.4 (t, J = 8.1 Hz), 132.0 (t, J = 5.3 Hz), 136.5, 137.8, 137.9 (d, J= 3.8 Hz), 141.8 (d, J = 1.9 Hz), 149.2, 156.8, 159.3, 160.5. 2-fluoro-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethyl) -1,1'-biphenyl (B2) 1 H-NMR (CDCl 3 ) δ: 8.55 (1H, dq, J = 5.0, 0.9 Hz), 7.98 (2H, dt, J = 8.5, 2.1 Hz), 7.71-7.46 (4H, m), 7.21 (2H, dt, J = 8.1, 3.2 Hz), 7.15 (1H, ddd, J) = 7.6, 5.0, 1.1 Hz), 7.08 (2H, ddd, J = 9.8, 7.3, 1.6 Hz), 4.05 (2H, t, J = 5.7 Hz), 3.51 (1H, s), 3.43-3.40 (2H, m), 3.10 (4H, q, J = 4.4 Hz) .; 13 C-NMR (CDCl 3 ) δ: 35.0, 40.0, 56.2, 58.3, 116.2 (d, J = 23.0 Hz), 121.4, 123.1, 126.5 ( d, J = 13.4 Hz), 128.0, 128.5 (d, J = 11.5 Hz), 129.9 (d, J = 2.9 Hz), 130.4 (t, J = 8.1 Hz), 132.0 (t, J = 5.3 Hz), 136.5, 137.8, 137.9 (d, J = 3.8 Hz), 141.8 (d, J = 1.9 Hz), 149.2, 156.8, 159.3, 160.5.

4'-(2-hydroxyethanesulfonyl)-3-(6-methylpyridin-2-yl)-ethyl-1,1'-biphenyl (B3) 1H-NMR (CDCl3) δ: 7.97 (2H, t, J = 4.4 Hz), 7.73 (2H, t, J = 4.4 Hz), 7.48 (1H, t, J = 7.6 Hz), 7.40 (3H, dq, J = 13.3, 4.3 Hz), 7.28 (1H, t, J = 3.7 Hz), 7.00 (1H, d, J = 7.3 Hz), 6.91 (1H, d, J= 7.8 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.51 (1H, br s), 3.41 (2H, t, J= 5.5 Hz), 3.10 (4H, s), 2.55 (3H, s).; 13C-NMR (CDCl3) δ: 24.4, 36.2, 40.0, 56.1, 58.3, 119.9, 120.8, 125.0, 127.6, 127.9, 128.4, 129.0, 129.0, 136.7, 137.3, 138.9, 142.5, 147.0, 157.8, 160.1. 4'-(2-hydroxyethanesulfonyl) -3- (6-methylpyridin-2-yl) -ethyl-1,1'-biphenyl (B3) 1 H-NMR (CDCl 3 ) δ: 7.97 (2H, t, J = 4.4 Hz), 7.73 (2H, t, J = 4.4 Hz), 7.48 (1H, t, J = 7.6 Hz), 7.40 (3H, dq, J = 13.3, 4.3 Hz), 7.28 (1H, t, J = 3.7 Hz), 7.00 (1H, d, J = 7.3 Hz), 6.91 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.51 (1H, br s), 3.41 ( 2H, t, J = 5.5 Hz), 3.10 (4H, s), 2.55 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 24.4, 36.2, 40.0, 56.1, 58.3, 119.9, 120.8, 125.0 , 127.6, 127.9, 128.4, 129.0, 129.0, 136.7, 137.3, 138.9, 142.5, 147.0, 157.8, 160.1.

2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(6-methylpyridin-2-yl)ethyl-1,1'-biphenyl (B4) 1H-NMR (CDCl3) δ: 7.98-7.95 (2H, m), 7.69 (2H, dd, J = 8.5, 1.6 Hz), 7.48 (1H, t, J = 7.8 Hz), 7.22 (2H, ddd, J = 12.0, 6.3, 2.6 Hz), 7.08 (1H, dd, J = 10.5, 8.2 Hz), 7.00 (1H, d, J = 7.8 Hz), 6.90 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.60 (1H, br s), 3.42 (2H, dd, J = 6.9, 4.6 Hz), 3.06 (4H, s), 2.54 (3H, s).; 13C-NMR (CDCl3) δ: 24.2, 35.2, 39.9, 56.0, 28.2, 116.1 (d, J = 23.0 Hz), 119.9, 120.9, 126.4 (d, J = 13.4 Hz), 127.9, 128.5 (d, J = 12.5 Hz), 129.8 (d, J = 2.9 Hz), 130.3 d, J = 7.7 Hz), 130.4 (d, J = 2.9 Hz), 132.0 (d, J = 3.8 Hz), 136.7, 137.8, 137.9 (d, J = 3.8 Hz), 141.7, 156.7, 157.8, 159.2, 159.8.; 19F-NMR (CDCl3) δ: 31.8. 2-fluoro-4'-(2-hydroxyethanesulfonyl) -5- (6-methylpyridin-2-yl) ethyl-1,1'-biphenyl (B4) 1 H-NMR (CDCl 3 ) δ: 7.98-7.95 (2H) , m), 7.69 (2H, dd, J = 8.5, 1.6 Hz), 7.48 (1H, t, J = 7.8 Hz), 7.22 (2H, ddd, J = 12.0, 6.3, 2.6 Hz), 7.08 (1H, 1H, dd, J = 10.5, 8.2 Hz), 7.00 (1H, d, J = 7.8 Hz), 6.90 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.60 (1H, br s), 3.42 (2H, dd, J = 6.9, 4.6 Hz), 3.06 (4H, s), 2.54 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 24.2, 35.2, 39.9, 56.0 , 28.2, 116.1 (d, J = 23.0 Hz), 119.9, 120.9, 126.4 (d, J = 13.4 Hz), 127.9, 128.5 (d, J = 12.5 Hz), 129.8 (d, J = 2.9 Hz), 130.3 d, J = 7.7 Hz), 130.4 (d, J = 2.9 Hz), 132.0 (d, J = 3.8 Hz), 136.7, 137.8, 137.9 (d, J = 3.8 Hz), 141.7, 156.7, 157.8, 159.2, 159.8 .; 19 F-NMR (CDCl 3 ) δ: 31.8.

3-tert-butyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B5) 1H-NMR (CDCl3) δ: 8.58 (1H, dt, J= 4.0, 1.4 Hz), 7.99-7.96 (2H, m), 7.76-7.73 (2H, m), 7.62 (2H, ddt, J = 24.7, 11.4, 4.0 Hz), 7.45 (1H, ddd, J = 14.4, 7.1, 4.1 Hz), 7.26 (2H, t, J = 2.1 Hz), 7.16-7.09 (2H, m), 4.04 (2H, t, J = 5.3 Hz), 3.42-3.39 (2H, m), 3.23 (1H, s), 3.13 (4H, s), 1.34 (9H, s).; 13C-NMR (CDCl3) δ: 31.3, 34.8, 36.8, 40.3, 56.3, 58.4, 121.3, 122.2, 123.1, 124.8,126.3, 128.1, 128.4, 128.6, 132.0, 136.4, 137.1, 138.8, 142.1, 147.7, 149.3, 152.1, 161.0. 3-tert-butyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethyl) -1,1'-biphenyl (B5) 1 H-NMR (CDCl 3 ) δ: 8.58 (1H, dt, J = 4.0, 1.4 Hz), 7.99-7.96 (2H, m), 7.76-7.73 (2H, m), 7.62 (2H, ddt, J = 24.7, 11.4, 4.0 Hz), 7.45 (1H, ddd, J = 14.4, 7.1, 4.1 Hz), 7.26 (2H, t, J = 2.1 Hz), 7.16-7.09 (2H, m), 4.04 (2H, t, J = 5.3 Hz), 3.42-3.39 (2H, m), 3.23 (1H, s), 3.13 (4H, s), 1.34 (9H, s) .; 13 C-NMR (CDCl 3 ) δ: 31.3, 34.8, 36.8, 40.3, 56.3, 58.4, 121.3, 122.2, 123.1, 124.8,126.3, 128.1, 128.4, 128.6, 132.0, 136.4, 137.1, 138.8, 142.1, 147.7, 149.3, 152.1, 161.0.

4'-(2-hydroxyethanesulfonyl)-3-methyl-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B6) 1H-NMR (CDCl3) δ: 8.56 (1H, d, J= 3.7 Hz), 7.97-7.94 (2H, m), 7.71 (2H, dd, J = 6.4, 1.8 Hz), 7.59 (1H, td, J = 7.8, 1.8 Hz), 7.22 (2H, d, J = 11.9 Hz), 7.13 (3H, td, J= 6.5, 4.4 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.49 (1H, s), 3.40 (2H, dd, J= 6.9, 4.6 Hz), 3.10 (4H, ddd, J = 14.7, 8.2, 4.6 Hz), 2.39 (3H, s).; 13C-NMR (CDCl3) δ: 21.4, 35.9, 40.1, 56.2, 58.3, 121.3, 123.0, 124.7, 125.8, 127.9, 128.3, 129.7, 136.4, 137.2, 138.8, 138.9, 142.3, 147.1, 149.2, 160.9. 4'-(2-hydroxyethanesulfonyl) -3-methyl-5-(pyridin-2-ylethyl) -1,1'-biphenyl (B6) 1 H-NMR (CDCl 3 ) δ: 8.56 (1H, d, J = 3.7 Hz), 7.97-7.94 (2H, m), 7.71 (2H, dd, J = 6.4, 1.8 Hz), 7.59 (1H, td, J = 7.8, 1.8 Hz), 7.22 (2H, d, J = 11.9) Hz), 7.13 (3H, td, J = 6.5, 4.4 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.49 (1H, s), 3.40 (2H, dd, J = 6.9, 4.6 Hz), 3.10 (4H, ddd, J = 14.7, 8.2, 4.6 Hz), 2.39 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 21.4, 35.9, 40.1, 56.2, 58.3, 121.3, 123.0, 124.7, 125.8, 127.9, 128.3, 129.7, 136.4, 137.2, 138.8, 138.9, 142.3, 147.1, 149.2, 160.9.

4'-(2-hydroxyethanesulfonyl)-3-(pyridin-2-ylethyl)-5-trifluoromethyl-1,1'-biphenyl (B7) 1H-NMR (CDCl3) δ: 8.59 (1H, dt, J= 4.3, 1.5 Hz), 8.02 (2H, dt, J = 8.5, 2.1 Hz), 7.74 (2H, dt, J = 8.7, 1.8 Hz), 7.66 (1H, s), 7.62-7.58 (2H, m), 7.51 (1H, s), 7.16 (1H, ddd, J= 7.4, 4.9, 1.0 Hz), 7.10 (1H, d, J = 7.8 Hz), 4.06 (2H, t, J = 5.0 Hz), 3.41 (2H, td, J = 4.1, 2.0 Hz), 3.23 (2H, dt, J = 9.5, 3.9 Hz), 3.18-3.13 (2H, m), 2.86 (1H, s).; 13C-NMR (CDCl3) δ: 35.6, 39.7, 56.2, 58.4, 121.5, 121.9 (q, J = 3.8 Hz), 123.1, 125.2, 125.5 (q, J = 3.5 Hz), 128.1, 128.5 (t, J = 9.6 Hz), 128.6 (d, J = 6.7 Hz), 130.9 (d, J = 1.9 Hz), 131.4, 131.9, 132.0 (t, J = 2.9 Hz), 132.7, 136.5, 138.3, 139.8, 143.5, 145.5, 149.4, 160.1.; 19F-NMR (CDCl3) δ: 37.6. 4'-(2-hydroxyethanesulfonyl) -3- (pyridin-2-ylethyl) -5-trifluoromethyl-1,1'-biphenyl (B7) 1 H-NMR (CDCl 3 ) δ: 8.59 (1H, dt, J = 4.3, 1.5 Hz), 8.02 (2H, dt, J = 8.5, 2.1 Hz), 7.74 (2H, dt, J = 8.7, 1.8 Hz), 7.66 (1H, s), 7.62-7.58 (2H, m), 7.51 (1H, s), 7.16 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 7.10 (1H, d, J = 7.8 Hz), 4.06 (2H, t, J = 5.0 Hz), 3.41 (2H) , td, J = 4.1, 2.0 Hz), 3.23 (2H, dt, J = 9.5, 3.9 Hz), 3.18-3.13 (2H, m), 2.86 (1H, s).; 13 C-NMR (CDCl 3 ) δ: 35.6, 39.7, 56.2, 58.4, 121.5, 121.9 (q, J = 3.8 Hz), 123.1, 125.2, 125.5 (q, J = 3.5 Hz), 128.1, 128.5 (t, J = 9.6 Hz), 128.6 ( d, J = 6.7 Hz), 130.9 (d, J = 1.9 Hz), 131.4, 131.9, 132.0 (t, J = 2.9 Hz), 132.7, 136.5, 138.3, 139.8, 143.5, 145.5, 149.4, 160.1.; 19 F-NMR (CDCl 3 ) δ: 37.6.

4'-(2-hydroxyethanesulfonyl)-4-methyl-3-(pyridin-2-ylethyl)-1,1'-biphenyl (B8) 1H-NMR (CDCl3) δ: 8.59-8.57 (1H, m), 7.95 (2H, dt, J = 8.7, 1.8 Hz), 7.70 (2H, dt, J = 8.7, 1.8 Hz), 7.59 (1H, td, J = 7.6, 1.8 Hz), 7.37-7.35 (2H, m), 7.27 (1H, s), 7.15 (1H, ddd, J = 7.6, 4.8, 1.1 Hz), 7.10 (1H, d, J = 7.8 Hz), 4.03 (2H, s), 3.41-3.38 (2H, m), 3.26 (1H, s), 3.12-3.09 (4H, m), 2.38 (3H, s).; 13C-NMR (CDCl3) δ: 19.0, 33.4, 38.8, 56.3, 58.4, 121.3, 123.0, 125.0, 127.7, 127.9, 128.4, 131.0, 136.4, 136.5, 137.0, 137.0, 140.1, 147.0, 149.3, 161.0. 4'-(2-hydroxyethanesulfonyl) -4-methyl-3- (pyridin-2-ylethyl) -1,1'-biphenyl (B8) 1 H-NMR (CDCl 3 ) δ: 8.59-8.57 (1H, m) , 7.95 (2H, dt, J = 8.7, 1.8 Hz), 7.70 (2H, dt, J = 8.7, 1.8 Hz), 7.59 (1H, td, J = 7.6, 1.8 Hz), 7.37-7.35 (2H, m) ), 7.27 (1H, s), 7.15 (1H, ddd, J = 7.6, 4.8, 1.1 Hz), 7.10 (1H, d, J = 7.8 Hz), 4.03 (2H, s), 3.41-3.38 (2H, s) m), 3.26 (1H, s), 3.12-3.09 (4H, m), 2.38 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 19.0, 33.4, 38.8, 56.3, 58.4, 121.3, 123.0 , 125.0, 127.7, 127.9, 128.4, 131.0, 136.4, 136.5, 137.0, 137.0, 140.1, 147.0, 149.3, 161.0.

4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl)ethyl-1,1'-biphenyl (B9) 1H-NMR (CDCl3) δ: 8.41 (1H, dd, J = 4.8, 1.6 Hz), 7.97 (2H, dt, J = 8.4, 1.9 Hz), 7.72 (2H, dt, J = 8.4, 1.9 Hz), 7.41 (4H, ddd, J = 14.0, 8.9, 3.2 Hz), 7.30 (1H, dt, J = 7.0, 1.6 Hz), 7.08 (1H, dd, J= 7.6, 4.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.46 (1H, s), 3.42-3.39 (2H, m), 3.11 (4H, s), 2.23 (3H, s).; 13C-NMR (CDCl3) δ: 18.7, 34.9, 37.1, 56.2, 58.4, 121.4, 125.0, 127.6, 128.0, 128.4, 128.6, 128.9, 129.1, 131.2, 131.9, 137.4, 137.7, 139.0, 142.8, 146.7, 147.0, 159.0. 4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl) ethyl-1,1'-biphenyl (B9) 1 H-NMR (CDCl 3 ) δ: 8.41 (1H, dd, J = 4.8) , 1.6 Hz), 7.97 (2H, dt, J = 8.4, 1.9 Hz), 7.72 (2H, dt, J = 8.4, 1.9 Hz), 7.41 (4H, ddd, J = 14.0, 8.9, 3.2 Hz), 7.30 (1H, dt, J = 7.0, 1.6 Hz), 7.08 (1H, dd, J = 7.6, 4.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.46 (1H, s), 3.42-3.39 ( 2H, m), 3.11 (4H, s), 2.23 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 18.7, 34.9, 37.1, 56.2, 58.4, 121.4, 125.0, 127.6, 128.0, 128.4, 128.6, 128.9, 129.1, 131.2, 131.9, 137.4, 137.7, 139.0, 142.8, 146.7, 147.0, 159.0.

4'-(2-hydroxyethanesulfonyl)-3-(6-methylpyridin-2-yl)ethyl-4-methyl-1,1'-biphenyl (B10) 1H-NMR (CDCl3) δ: 7.95 (2H, dt, J = 8.7, 1.8 Hz), 7.72-7.69 (2H, m), 7.47 (1H, t, J = 7.8 Hz), 7.36 (2H, dt, J = 9.8, 3.4 Hz), 7.25 (1H, t, J = 5.3 Hz), 7.00 (1H, d, J = 7.3 Hz), 6.89 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m), 3.23 (1H, s), 3.08 (4H, dt, J = 12.7, 4.9 Hz), 2.56 (3H, s), 2.37 (3H, s).; 13C-NMR (CDCl3) δ: 19.0, 24.5, 33.5, 38.7, 56.3, 58.4, 119.8, 120.8, 124.9, 127.7, 127.9, 128.4, 130.9, 136.4, 136.6, 136.9, 137.0, 140.6, 147.0, 157.9, 160.4. 4'-(2-hydroxyethanesulfonyl) -3- (6-methylpyridin-2-yl) ethyl-4-methyl-1,1'-biphenyl (B10) 1 H-NMR (CDCl 3 ) δ: 7.95 (2H, dt) , J = 8.7, 1.8 Hz), 7.72-7.69 (2H, m), 7.47 (1H, t, J = 7.8 Hz), 7.36 (2H, dt, J = 9.8, 3.4 Hz), 7.25 (1H, t, J = 5.3 Hz), 7.00 (1H, d, J = 7.3 Hz), 6.89 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m) , 3.23 (1H, s), 3.08 (4H, dt, J = 12.7, 4.9 Hz), 2.56 (3H, s), 2.37 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 19.0, 24.5 , 33.5, 38.7, 56.3, 58.4, 119.8, 120.8, 124.9, 127.7, 127.9, 128.4, 130.9, 136.4, 136.6, 136.9, 137.0, 140.6, 147.0, 157.9, 160.4.

4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl)ethyl-4-methyl-1,1'-biphenyl (B11) 1H-NMR (CDCl3) δ: 8.44 (1H, dd, J = 5.0, 1.4 Hz), 7.97-7.93 (2H, m), 7.71-7.69 (2H, m), 7.67-7.63 (1H, m), 7.49-7.44 (1H, m), 7.35 (1H, dd, J= 5.0, 1.8 Hz), 7.27 (1H, t, J = 3.9 Hz), 7.08 (1H, dd, J = 7.6, 4.8 Hz), 4.03 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m), 3.22 (1H, br s), 3.14-3.05 (4H, m), 2.41 (3H, s), 2.21 (3H, s).; 13C-NMR (CDCl3) δ: 18.7, 19.0, 32.4, 35.8, 56.3, 58.4, 121.4, 125.0, 127.7, 128.1, 128.4, 128.6, 131.0, 131.2, 132.0, 132.1, 136.6, 137.0, 137.7, 140.9, 146.8, 147.0, 159.2. 4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl) ethyl-4-methyl-1,1'-biphenyl (B11) 1 H-NMR (CDCl 3 ) δ: 8.44 (1H, dd) , J = 5.0, 1.4 Hz), 7.97-7.93 (2H, m), 7.71-7.69 (2H, m), 7.67-7.63 (1H, m), 7.49-7.44 (1H, m), 7.35 (1H, dd) , J = 5.0, 1.8 Hz), 7.27 (1H, t, J = 3.9 Hz), 7.08 (1H, dd, J = 7.6, 4.8 Hz), 4.03 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m), 3.22 (1H, br s), 3.14-3.05 (4H, m), 2.41 (3H, s), 2.21 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 18.7, 19.0, 32.4, 35.8, 56.3, 58.4, 121.4, 125.0, 127.7, 128.1, 128.4, 128.6, 131.0, 131.2, 132.0, 132.1, 136.6, 137.0, 137.7, 140.9, 146.8, 147.0, 159.2.

4'-(2-hydroxyethanesulfonyl)-2-methyl-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B12) 1H-NMR (CDCl3) δ: 8.54 (1H, dq, J= 4.9, 0.9 Hz), 7.96 (2H, dt, J = 8.6, 1.9 Hz), 7.59 (1H, td, J = 7.7, 1.8 Hz), 7.49 (2H, dt, J = 8.5, 1.9 Hz), 7.22-7.10 (4H, m), 7.02 (1H, d, J = 1.8 Hz), 4.06 (2H, dd, J = 7.0, 4.2 Hz), 3.54 (1H, br s), 3.43 (2H, dt, J = 5.8, 2.7 Hz), 3.13-3.03 (4H, m), 2.22 (3H, s).; 13C-NMR (CDCl3) δ: 19.8, 35.4, 40.0, 56.2, 58.3, 121.2, 123.0, 127.7, 128.3, 129.6, 130.1, 130.7, 132.5, 136.4, 137.1, 139.2, 139.6, 148.1, 149.1, 160.9. 4'-(2-hydroxyethanesulfonyl) -2-methyl-5- (pyridin-2-ylethyl) -1,1'-biphenyl (B12) 1 H-NMR (CDCl 3 ) δ: 8.54 (1H, dq, J = 4.9, 0.9 Hz), 7.96 (2H, dt, J = 8.6, 1.9 Hz), 7.59 (1H, td, J = 7.7, 1.8 Hz), 7.49 (2H, dt, J = 8.5, 1.9 Hz), 7.22- 7.10 (4H, m), 7.02 (1H, d, J = 1.8 Hz), 4.06 (2H, dd, J = 7.0, 4.2 Hz), 3.54 (1H, br s), 3.43 (2H, dt, J = 5.8) , 2.7 Hz), 3.13-3.03 (4H, m), 2.22 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 19.8, 35.4, 40.0, 56.2, 58.3, 121.2, 123.0, 127.7, 128.3, 129.6, 130.1, 130.7, 132.5, 136.4, 137.1, 139.2, 139.6, 148.1, 149.1, 160.9.

4'-(2-hydroxyethanesulfonyl)-4-propyl-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B14) 1H-NMR (CDCl3) δ: 8.58 (1H, dq, J= 4.9, 0.9 Hz), 7.95 (2H, dt, J = 8.6, 1.9 Hz), 7.70 (2H, dt, J = 8.6, 2.0 Hz), 7.60 (1H, td, J = 7.6, 1.9 Hz), 7.39 (2H, t, J = 4.8 Hz), 7.27 (1H, t, J = 3.9 Hz), 7.16 (1H, ddd, J = 7.6, 4.9, 1.1 Hz), 7.10 (1H, d, J = 7.6 Hz), 4.04 (2H, t, J = 5.4 Hz), 3.44 (1H, s), 3.41-3.39 (2H, m), 3.16-3.07 (4H, m), 2.66 (2H, dd, J = 8.8, 6.9 Hz), 1.66 (2H, td, J = 15.1, 7.5 Hz), 1.01 (3H, t, J = 7.3 Hz).; 13C-NMR (CDCl3) δ: 14.1, 24.2, 32.8, 34.3, 39.7, 56.2, 58.3, 121.3, 123.0, 124.9, 127.6, 128.2, 128.4, 128.6, 130.0, 132.0, 136.3, 136.4, 136.9, 140.0, 141.4, 146.9, 149.3, 160.9. 4'-(2-hydroxyethanesulfonyl) -4-propyl-5- (pyridin-2-ylethyl) -1,1'-biphenyl (B14) 1 H-NMR (CDCl 3 ) δ: 8.58 (1H, dq, J = 4.9, 0.9 Hz), 7.95 (2H, dt, J = 8.6, 1.9 Hz), 7.70 (2H, dt, J = 8.6, 2.0 Hz), 7.60 (1H, td, J = 7.6, 1.9 Hz), 7.39 ( 2H, t, J = 4.8 Hz), 7.27 (1H, t, J = 3.9 Hz), 7.16 (1H, ddd, J = 7.6, 4.9, 1.1 Hz), 7.10 (1H, d, J = 7.6 Hz), 4.04 (2H, t, J = 5.4 Hz), 3.44 (1H, s), 3.41-3.39 (2H, m), 3.16-3.07 (4H, m), 2.66 (2H, dd, J = 8.8, 6.9 Hz) , 1.66 (2H, td, J = 15.1, 7.5 Hz), 1.01 (3H, t, J = 7.3 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.1, 24.2, 32.8, 34.3, 39.7, 56.2, 58.3, 121.3, 123.0, 124.9, 127.6, 128.2, 128.4, 128.6, 130.0, 132.0, 136.3, 136.4, 136.9, 140.0, 141.4, 146.9, 149.3, 160.9.

4-ethoxy-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B15) 1H-NMR (CDCl3) δ: 8.55 (1H, dq, J= 4.9, 0.9 Hz), 7.92 (2H, t, J = 4.3 Hz), 7.66 (2H, dd, J = 6.8, 1.8 Hz), 7.57 (1H, td, J = 7.6, 1.9 Hz), 7.42 (1H, dd, J = 8.6, 2.5 Hz), 7.34 (1H, d, J = 2.5 Hz), 7.14-7.09 (2H, m), 6.92 (1H, d, J= 8.6 Hz), 4.10 (2H, q, J = 7.0 Hz), 4.02 (2H, t, J = 5.5 Hz), 3.33 (3H, dd, J = 27.1, 21.7 Hz), 3.11 (4H, s), 1.46 (3H, t, J = 7.0 Hz).; 13C-NMR (CDCl3) δ: 14.8, 30.8, 38.3, 56.3, 58.4, 63.6, 111.5, 121.1, 123.0, 126.2, 127.2, 128.4, 129.0, 130.5, 130.7, 136.3, 146.8, 149.1, 157.6, 161.6. 4-ethoxy-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethyl) -1,1'-biphenyl (B15) 1 H-NMR (CDCl 3 ) δ: 8.55 (1H, dq, J = 4.9, 0.9 Hz), 7.92 (2H, t, J = 4.3 Hz), 7.66 (2H, dd, J = 6.8, 1.8 Hz), 7.57 (1H, td, J = 7.6, 1.9 Hz), 7.42 (1H, dd, J = 8.6, 2.5 Hz), 7.34 (1H, d, J = 2.5 Hz), 7.14-7.09 (2H, m), 6.92 (1H, d, J = 8.6 Hz), 4.10 (2H, q, J) = 7.0 Hz), 4.02 (2H, t, J = 5.5 Hz), 3.33 (3H, dd, J = 27.1, 21.7 Hz), 3.11 (4H, s), 1.46 (3H, t, J = 7.0 Hz). 13 C-NMR (CDCl 3 ) δ: 14.8, 30.8, 38.3, 56.3, 58.4, 63.6, 111.5, 121.1, 123.0, 126.2, 127.2, 128.4, 129.0, 130.5, 130.7, 136.3, 146.8, 149.1, 157.6, 161.6 ..

4'-(2-hydroxyethanesulfonyl)-4-pentyl-3-(pyridin-2-ylethyl)-1,1'-biphenyl (B16) 1H-NMR (CDCl3) δ: 8.58 (1H, t, J= 2.5 Hz), 7.95 (2H, t, J = 4.1 Hz), 7.70 (2H, t, J = 4.4 Hz), 7.59 (1H, td, J = 7.6, 1.8 Hz), 7.39 (2H, t, J = 4.8 Hz), 7.27 (1H, t, J = 3.7 Hz), 7.15 (1H, td, J = 6.2, 1.1 Hz), 7.09 (1H, d, J = 7.8 Hz), 4.04 (2H, s), 3.40 (2H, dd, J = 6.9, 4.1 Hz), 3.29 (1H, s), 3.12 (4H, ddd, J = 14.4, 8.0, 4.4 Hz), 2.67 (2H, t, J = 7.8 Hz), 1.61 (2H, dd, J = 15.6, 7.3 Hz), 1.38 (4H, dd, J = 7.1, 3.4 Hz), 0.91 (3H, t, J = 7.1 Hz).; 13C-NMR (CDCl3) δ: 14.0, 22.5, 30.8, 31.8, 32.3, 32.8, 39.7, 56.3, 58.4, 121.3, 123.0, 125.0, 127.7, 128.3, 130.0, 136.3, 136.4, 136.9, 140.0, 141.7, 147.0, 149.3, 161.0. 4'-(2-hydroxyethanesulfonyl) -4-pentyl-3- (pyridin-2-ylethyl) -1,1'-biphenyl (B16) 1 H-NMR (CDCl 3 ) δ: 8.58 (1H, t, J = 2.5 Hz), 7.95 (2H, t, J = 4.1 Hz), 7.70 (2H, t, J = 4.4 Hz), 7.59 (1H, td, J = 7.6, 1.8 Hz), 7.39 (2H, t, J = 4.8 Hz), 7.27 (1H, t, J = 3.7 Hz), 7.15 (1H, td, J = 6.2, 1.1 Hz), 7.09 (1H, d, J = 7.8 Hz), 4.04 (2H, s), 3.40 (2H, dd, J = 6.9, 4.1 Hz), 3.29 (1H, s), 3.12 (4H, ddd, J = 14.4, 8.0, 4.4 Hz), 2.67 (2H, t, J = 7.8 Hz), 1.61 ( 2H, dd, J = 15.6, 7.3 Hz), 1.38 (4H, dd, J = 7.1, 3.4 Hz), 0.91 (3H, t, J = 7.1 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0 , 22.5, 30.8, 31.8, 32.3, 32.8, 39.7, 56.3, 58.4, 121.3, 123.0, 125.0, 127.7, 128.3, 130.0, 136.3, 136.4, 136.9, 140.0, 141.7, 147.0, 149.3, 161.0.

4'-(2-hydroxyethanesulfonyl)-4-iso-propyl-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B17) 1H-NMR (CDCl3) δ:8.59 (1H, dd, J = 5.0, 0.9 Hz), 7.95 (2H, dd, J = 6.6, 2.1 Hz), 7.72 (2H, dd, J = 6.4, 1.8 Hz), 7.59 (1H, td, J = 7.6, 2.0 Hz), 7.45 (1H, dd, J = 8.0, 2.1 Hz), 7.39 (2H, t, J = 5.3 Hz), 7.15 (1H, td, J = 6.2, 1.1 Hz), 7.09 (1H, d, J = 7.8 Hz), 4.04 (2H, s), 3.40 (2H, dd, J = 7.1, 3.9 Hz), 3.27 (1H, dd, J = 13.7, 6.9 Hz), 3.19-3.07 (5H, m), 1.27 (6H, d, J = 6.4 Hz).; 13C-NMR (CDCl3) δ: 24.0, 28.6, 32.9, 40.2, 56.3, 58.4, 121.3, 123.0, 125.4, 126.2, 127.7, 128.4, 128.5, 136.1, 136.4, 137.0, 139.2, 147.0, 147.7, 149.4, 161.0. 4'-(2-hydroxyethanesulfonyl) -4-iso-propyl-5- (pyridin-2-ylethyl) -1,1'-biphenyl (B17) 1 H-NMR (CDCl 3 ) δ: 8.59 (1H, dd, J = 5.0, 0.9 Hz), 7.95 (2H, dd, J = 6.6, 2.1 Hz), 7.72 (2H, dd, J = 6.4, 1.8 Hz), 7.59 (1H, td, J = 7.6, 2.0 Hz), 7.45 (1H, dd, J = 8.0, 2.1 Hz), 7.39 (2H, t, J = 5.3 Hz), 7.15 (1H, td, J = 6.2, 1.1 Hz), 7.09 (1H, d, J = 7.8 Hz) ), 4.04 (2H, s), 3.40 (2H, dd, J = 7.1, 3.9 Hz), 3.27 (1H, dd, J = 13.7, 6.9 Hz), 3.19-3.07 (5H, m), 1.27 (6H, d, J = 6.4 Hz) .; 13 C-NMR (CDCl 3 ) δ: 24.0, 28.6, 32.9, 40.2, 56.3, 58.4, 121.3, 123.0, 125.4, 126.2, 127.7, 128.4, 128.5, 136.1, 136.4, 137.0 , 139.2, 147.0, 147.7, 149.4, 161.0.

4-iso-butyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B18) 1H-NMR (CDCl3) δ:8.58 (1H, d, J = 4.1 Hz), 7.96-7.94 (2H, m), 7.71 (2H, dt, J = 8.7, 1.8 Hz), 7.59 (1H, td, J = 7.8, 1.8 Hz), 7.38 (2H, dd, J = 6.0, 2.3 Hz), 7.23 (1H, t, J = 4.4 Hz), 7.15 (1H, dt, J = 5.8, 2.7 Hz), 7.08 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m), 3.18 (1H, s), 3.11 (4H, tt, J = 11.7, 4.3 Hz), 2.56 (2H, d, J = 7.3 Hz), 1.94-1.87 (1H, m), 0.96 (6H, d, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 22.6, 29.8, 32.8, 39.8, 41.5, 56.3, 58.4, 121.3, 123.0, 124.7, 127.7, 128.3, 128.4, 130.9, 136.3, 136.4, 136.9, 140.4, 140.5, 147.0, 149.4, 161.0. 4-iso-butyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethyl) -1,1'-biphenyl (B18) 1 H-NMR (CDCl 3 ) δ: 8.58 (1H, d, J = 4.1 Hz), 7.96-7.94 (2H, m), 7.71 (2H, dt, J = 8.7, 1.8 Hz), 7.59 (1H, td, J = 7.8, 1.8 Hz), 7.38 (2H, dd, J) = 6.0, 2.3 Hz), 7.23 (1H, t, J = 4.4 Hz), 7.15 (1H, dt, J = 5.8, 2.7 Hz), 7.08 (1H, d, J = 7.8 Hz), 4.04 (2H, t) , J = 5.5 Hz), 3.41-3.38 (2H, m), 3.18 (1H, s), 3.11 (4H, tt, J = 11.7, 4.3 Hz), 2.56 (2H, d, J = 7.3 Hz), 1.94 -1.87 (1H, m), 0.96 (6H, d, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 22.6, 29.8, 32.8, 39.8, 41.5, 56.3, 58.4, 121.3, 123.0, 124.7 , 127.7, 128.3, 128.4, 130.9, 136.3, 136.4, 136.9, 140.4, 140.5, 147.0, 149.4, 161.0.

4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl)ethyl-4-propyl-1,1'-biphenyl (B19) 1H-NMR (CDCl3) δ:8.44 (1H, dd, J = 5.0, 1.2 Hz), 7.95 (2H, dt, J = 8.6, 2.0 Hz), 7.70 (2H, dt, J = 8.7, 2.0 Hz), 7.44-7.37 (3H, m), 7.28 (1H, t, J= 4.0 Hz), 7.08 (1H, dd, J = 7.6, 4.7 Hz), 4.04 (2H, t, J = 5.6 Hz), 3.40 (2H, dt, J = 5.8, 2.5 Hz), 3.35 (1H, br s), 3.15-3.05 (4H, m), 2.69 (2H, dd, J = 8.9, 6.7 Hz), 2.21 (3H, s), 1.72-1.63 (2H, m), 1.02 (3H, t, J = 7.3 Hz).; 13C-NMR (CDCl3) δ: 14.2, 18.7, 24.3, 31.8, 34.4, 36.8 56.3, 58.4, 121.4, 125.0, 127.7, 128.4, 128.4, 128.4, 130.0, 131.2, 132.0, 136.4, 137.0, 137.7, 140.4, 141.4, 146.8, 146.9, 159.3. 4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl) ethyl-4-propyl-1,1'-biphenyl (B19) 1 H-NMR (CDCl 3 ) δ: 8.44 (1H, dd) , J = 5.0, 1.2 Hz), 7.95 (2H, dt, J = 8.6, 2.0 Hz), 7.70 (2H, dt, J = 8.7, 2.0 Hz), 7.44-7.37 (3H, m), 7.28 (1H, t, J = 4.0 Hz), 7.08 (1H, dd, J = 7.6, 4.7 Hz), 4.04 (2H, t, J = 5.6 Hz), 3.40 (2H, dt, J = 5.8, 2.5 Hz), 3.35 ( 1H, br s), 3.15-3.05 (4H, m), 2.69 (2H, dd, J = 8.9, 6.7 Hz), 2.21 (3H, s), 1.72-1.63 (2H, m), 1.02 (3H, t) , J = 7.3 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.2, 18.7, 24.3, 31.8, 34.4, 36.8 56.3, 58.4, 121.4, 125.0, 127.7, 128.4, 128.4, 128.4, 130.0, 131.2, 132.0 , 136.4, 137.0, 137.7, 140.4, 141.4, 146.8, 146.9, 159.3.

4'-(2-hydroxyethanesulfonyl)-3-(3-penthylpyridin-2-yl)ethyl-4-propyl-1,1'-biphenyl (B21) 1H-NMR (CDCl3) δ:8.45 (1H, dd, J = 4.8, 1.7 Hz), 7.97-7.94 (2H, m), 7.70 (2H, dt, J= 8.6, 2.0 Hz), 7.45-7.38 (3H, m), 7.28 (1H, t, J = 5.0 Hz), 7.11 (1H, dd, J = 7.6, 4.8 Hz), 4.06-4.03 (2H, m), 3.41-3.38 (2H, m), 3.31 (1H, br s), 3.12 (4H, ddt, J = 19.2, 9.7, 3.6 Hz), 2.69 (2H, dd, J = 8.9, 7.0 Hz), 2.51 (2H, t, J = 7.9 Hz), 1.72-1.63 (2H, m), 1.54-1.46 (2H, m), 1.29 (4H, tt, J = 9.6, 3.6 Hz), 1.02 (3H, dd, J = 9.3, 5.2 Hz), 0.87 (3H, tt, J = 7.1, 2.3 Hz).; 13C-NMR (CDCl3) δ: 13.9, 14.2, 22.4, 24.3, 30.2, 31.7, 32.0,32.5, 34.4, 36.2, 56.3, 58.4, 121.4, 125.0, 127.7, 127.9, 128.4, 128.4, 129.4, 130.0, 135.8, 136.4, 136.8, 137.0, 140.5, 141.4, 146.7, 146.9, 158.8. 4'-(2-hydroxyethanesulfonyl) -3- (3-penthylpyridin-2-yl) ethyl-4-propyl-1,1'-biphenyl (B21) 1 H-NMR (CDCl 3 ) δ: 8.45 (1H, dd) , J = 4.8, 1.7 Hz), 7.97-7.94 (2H, m), 7.70 (2H, dt, J = 8.6, 2.0 Hz), 7.45-7.38 (3H, m), 7.28 (1H, t, J = 5.0) Hz), 7.11 (1H, dd, J = 7.6, 4.8 Hz), 4.06-4.03 (2H, m), 3.41-3.38 (2H, m), 3.31 (1H, br s), 3.12 (4H, ddt, J) = 19.2, 9.7, 3.6 Hz), 2.69 (2H, dd, J = 8.9, 7.0 Hz), 2.51 (2H, t, J = 7.9 Hz), 1.72-1.63 (2H, m), 1.54-1.46 (2H, m), 1.29 (4H, tt, J = 9.6, 3.6 Hz), 1.02 (3H, dd, J = 9.3, 5.2 Hz), 0.87 (3H, tt, J = 7.1, 2.3 Hz) .; 13 C-NMR (CDCl 3 ) δ: 13.9, 14.2, 22.4, 24.3, 30.2, 31.7, 32.0, 32.5, 34.4, 36.2, 56.3, 58.4, 121.4, 125.0, 127.7, 127.9, 128.4, 128.4, 129.4, 130.0, 135.8, 136.4, 136.8, 137.0, 140.5, 141.4, 146.7, 146.9, 158.8.

4-heptyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B22) 1H-NMR (CDCl3) δ:8.57 (1H, t, J = 2.5 Hz), 7.95 (2H, d, J = 8.2 Hz), 7.70 (2H, t, J= 4.4 Hz), 7.59 (1H, td, J = 7.8, 1.8 Hz), 7.38 (2H, t, J = 4.4 Hz), 7.27 (2H, t, J = 4.1 Hz), 7.17-7.14 (1H, m), 7.09 (1H, d, J= 7.8 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.63 (1H, s), 3.40 (2H, dd, J= 7.1, 4.4 Hz), 3.16-3.07 (4H, m), 2.67 (2H, t, J = 8.0 Hz), 1.65-1.58 (2H, m), 1.44-1.28 (8H, m), 0.88 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 14.0, 22.6, 29.1, 29.6, 31.7, 32.3, 32.8, 39.6, 56.1, 58.3, 121.3, 123.0, 124.9, 127.6, 128.2, 128.3, 129.9, 136.2, 136.5, 137.0, 139.9, 141.6, 146.8, 149.2, 160.9. 4-heptyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethyl) -1,1'-biphenyl (B22) 1 H-NMR (CDCl 3 ) δ: 8.57 (1H, t, J = 2.5 Hz), 7.95 (2H, d, J = 8.2 Hz), 7.70 (2H, t, J = 4.4 Hz), 7.59 (1H, td, J = 7.8, 1.8 Hz), 7.38 (2H, t, J = 4.4 Hz), 7.27 (2H, t, J = 4.1 Hz), 7.17-7.14 (1H, m), 7.09 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.63 (1H, s), 3.40 (2H, dd, J = 7.1, 4.4 Hz), 3.16-3.07 (4H, m), 2.67 (2H, t, J = 8.0 Hz), 1.65-1.58 (2H, m), 1.44-1.28 (8H, m), 0.88 (3H, t, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 22.6, 29.1, 29.6, 31.7, 32.3, 32.8, 39.6, 56.1, 58.3, 121.3, 123.0, 124.9, 127.6, 128.2, 128.3, 129.9, 136.2, 136.5, 137.0, 139.9, 141.6, 146.8, 149.2, 160.9.

4'-(2-hydroxyethanesulfonyl)-4-octyl-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B23) 1H-NMR (CDCl3) δ:8.58 (1H, t, J = 2.5 Hz), 7.96-7.93 (2H, m), 7.73-7.69 (2H, m), 7.59 (1H, td, J = 7.6, 1.8 Hz), 7.39 (2H, t, J = 4.8 Hz), 7.27 (1H, t, J = 3.9 Hz), 7.17-7.14 (1H, m), 7.09 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (3H, m), 3.16-3.07 (4H, m), 2.67 (2H, t, J= 8.0 Hz), 1.65-1.58 (2H, m), 1.35 (10H, dq, J = 33.8, 8.3 Hz), 0.88 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 14.1, 22.6, 29.2, 29.4, 29.7, 31.1, 31.8, 32.3, 32.8, 39.7, 56.2, 58.3, 121.3, 123.0, 125.0, 127.6, 128.2, 128.4, 130.0, 136.3, 136.4, 136.9, 140.0, 141.7, 146.9, 149.3, 161.0. 4'-(2-hydroxyethanesulfonyl) -4-octyl-5- (pyridin-2-ylethyl) -1,1'-biphenyl (B23) 1 H-NMR (CDCl 3 ) δ: 8.58 (1H, t, J = 2.5 Hz), 7.96-7.93 (2H, m), 7.73-7.69 (2H, m), 7.59 (1H, td, J = 7.6, 1.8 Hz), 7.39 (2H, t, J = 4.8 Hz), 7.27 ( 1H, t, J = 3.9 Hz), 7.17-7.14 (1H, m), 7.09 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (3H, m) ), 3.16-3.07 (4H, m), 2.67 (2H, t, J = 8.0 Hz), 1.65-1.58 (2H, m), 1.35 (10H, dq, J = 33.8, 8.3 Hz), 0.88 (3H, t, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.1, 22.6, 29.2, 29.4, 29.7, 31.1, 31.8, 32.3, 32.8, 39.7, 56.2, 58.3, 121.3, 123.0, 125.0, 127.6 , 128.2, 128.4, 130.0, 136.3, 136.4, 136.9, 140.0, 141.7, 146.9, 149.3, 161.0.

4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B24) 1H-NMR (CDCl3) δ:8.58 (1H, d, J = 5.0 Hz), 7.94 (2H, d, J = 8.2 Hz), 7.70 (2H, d, J= 8.2 Hz), 7.58 (1H, td, J = 7.6, 1.8 Hz), 7.42 (1H, dd, J = 8.0, 2.1 Hz), 7.35 (2H, dd, J = 6.9, 5.0 Hz), 7.16-7.13 (1H, m), 7.05 (1H, d, J = 7.8 Hz), 4.03 (2H, t, J = 5.5 Hz), 3.58 (1H, s), 3.40 (2H, dd, J = 7.3, 4.1 Hz), 3.19-3.14 (2H, m), 3.10-3.06 (2H, m), 2.77 (1H, t, J = 9.8 Hz), 1.79 (5H, dt, J = 38.8, 12.7 Hz), 1.38 (5H, dtd, J= 65.2, 19.6, 9.5 Hz).; 13C-NMR (CDCl3) δ: 26.1, 26.9, 32.8, 34.3, 39.4, 40.1, 56.2, 58.3, 121.3, 123.1, 125.2, 126.8, 127.6, 128.3, 128.4, 131.9, 132.0, 135.9, 136.4, 136.9, 139.1, 146.6, 146.8, 149.2, 160.9. 4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-ylethyl) -1,1'-biphenyl (B24) 1 H-NMR (CDCl 3 ) δ: 8.58 (1H, d, J = 5.0 Hz), 7.94 (2H, d, J = 8.2 Hz), 7.70 (2H, d, J = 8.2 Hz), 7.58 (1H, td, J = 7.6, 1.8 Hz), 7.42 (1H, dd, J = 8.0, 2.1 Hz), 7.35 (2H, dd, J = 6.9, 5.0 Hz), 7.16-7.13 (1H, m), 7.05 (1H, d, J = 7.8 Hz), 4.03 (2H, t, J) = 5.5 Hz), 3.58 (1H, s), 3.40 (2H, dd, J = 7.3, 4.1 Hz), 3.19-3.14 (2H, m), 3.10-3.06 (2H, m), 2.77 (1H, t, J = 9.8 Hz), 1.79 (5H, dt, J = 38.8, 12.7 Hz), 1.38 (5H, dtd, J = 65.2, 19.6, 9.5 Hz) .; 13 C-NMR (CDCl 3 ) δ: 26.1, 26.9 , 32.8, 34.3, 39.4, 40.1, 56.2, 58.3, 121.3, 123.1, 125.2, 126.8, 127.6, 128.3, 128.4, 131.9, 132.0, 135.9, 136.4, 136.9, 139.1, 146.6, 146.8, 149.2, 160.9.

4'-(2-hydroxyethanesulfonyl)-4-cyclo-pentyl-5-(pyridin-2-ylethyl)-1,1'-biphenyl (B25) 1H-NMR (CDCl3) δ:8.59 (1H, dq, J = 5.0, 0.9 Hz), 7.95 (2H, dt, J = 8.7, 1.8 Hz), 7.71 (2H, dt, J = 8.7, 1.8 Hz), 7.59 (1H, td, J = 7.8, 1.8 Hz), 7.44 (1H, dd, J = 8.2, 1.8 Hz), 7.39 (1H, d, J = 7.8 Hz), 7.36 (1H, d, J = 2.3 Hz), 7.15 (1H, ddd, J = 7.6, 5.0, 1.1 Hz), 7.08 (1H, dd, J = 7.8, 0.9 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.40 (2H, td, J = 4.1, 2.1 Hz), 3.34-3.16 (4H, m), 3.13-3.06 (2H, m), 2.09-2.02 (2H, m), 1.86 (2H, ddt, J = 23.1, 13.3, 4.6 Hz), 1.80-1.69 (2H, m), 1.62 (2H, dtd, J = 20.1, 7.8, 3.7 Hz).; 13C-NMR (CDCl3) δ: 25.9, 33.2, 35.1, 40.2, 40.7, 56.3, 58.3, 121.3, 123.1, 125.4, 126.9, 127.7, 128.3, 128.4, 135.9, 136.4, 136.9, 140.0, 145.6, 146.9, 149.3, 161.0. 4'-(2-hydroxyethanesulfonyl) -4-cyclo-pentyl-5- (pyridin-2-ylethyl) -1,1'-biphenyl (B25) 1 H-NMR (CDCl 3 ) δ: 8.59 (1H, dq, J = 5.0, 0.9 Hz), 7.95 (2H, dt, J = 8.7, 1.8 Hz), 7.71 (2H, dt, J = 8.7, 1.8 Hz), 7.59 (1H, td, J = 7.8, 1.8 Hz), 7.44 (1H, dd, J = 8.2, 1.8 Hz), 7.39 (1H, d, J = 7.8 Hz), 7.36 (1H, d, J = 2.3 Hz), 7.15 (1H, ddd, J = 7.6, 5.0, 1.1 Hz), 7.08 (1H, dd, J = 7.8, 0.9 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.40 (2H, td, J = 4.1, 2.1 Hz), 3.34-3.16 (4H, m), 3.13-3.06 (2H, m), 2.09-2.02 (2H, m), 1.86 (2H, ddt, J = 23.1, 13.3, 4.6 Hz), 1.80-1.69 (2H, m), 1.62 (2H, m) dtd, J = 20.1, 7.8, 3.7 Hz) .; 13 C-NMR (CDCl 3 ) δ: 25.9, 33.2, 35.1, 40.2, 40.7, 56.3, 58.3, 121.3, 123.1, 125.4, 126.9, 127.7, 128.3, 128.4 , 135.9, 136.4, 136.9, 140.0, 145.6, 146.9, 149.3, 161.0.

(3)Ｃ１～Ｃ２５の合成
Ｃ１～Ｃ２５の合成は下記合成法により合成した。 (3) Synthesis of C1 to C25 The synthesis of C1 to C25 was synthesized by the following synthetic method.

Figure 0007060775000162
Figure 0007060775000162

合成したC1～C25のNMRを下記に示す。 The synthesized NMR of C1 to C25 is shown below.

(E)-4'-(2-hydroxyethanesulfonyl)-3-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C1) 1H-NMR (CDCl3) δ: 8.60 (1H, dd, J= 4.8, 1.0 Hz), 7.99 (2H, dt, J = 8.8, 1.9 Hz), 7.79-7.76 (3H, m), 7.70-7.61 (3H, m), 7.54-7.41 (3H, m), 7.25 (1H, d, J = 21.0 Hz), 7.17 (1H, ddd, J = 7.5, 4.9, 1.0 Hz), 4.06-4.03 (2H, m), 3.43-3.40 (3H, m).; 13C-NMR (CDCl3) δ: 56.2, 58.3, 122.2, 122.3, 126.0, 127.2, 128.0, 128.5, 128.7, 129.4, 132.0, 136.7, 137.4, 137.7, 139.4, 146.6, 149.6, 155.1. (E) -4'-(2-hydroxyethanesulfonyl) -3- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C1) 1 H-NMR (CDCl 3 ) δ: 8.60 (1H, dd, J = 4.8, 1.0 Hz), 7.99 (2H, dt, J = 8.8, 1.9 Hz), 7.79-7.76 (3H, m), 7.70-7.61 (3H, m), 7.54-7.41 (3H, m) , 7.25 (1H, d, J = 21.0 Hz), 7.17 (1H, ddd, J = 7.5, 4.9, 1.0 Hz), 4.06-4.03 (2H, m), 3.43-3.40 (3H, m) .; 13 C -NMR (CDCl 3 ) δ: 56.2, 58.3, 122.2, 122.3, 126.0, 127.2, 128.0, 128.5, 128.7, 129.4, 132.0, 136.7, 137.4, 137.7, 139.4, 146.6, 149.6, 155.1.

(E)-2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C2) 1H-NMR (CDCl3) δ: 8.60 (1H, dd, J= 5.0, 0.9 Hz), 8.01 (2H, dt, J = 8.7, 1.8 Hz), 7.77 (2H, dd, J = 8.2, 1.4 Hz), 7.71-7.44 (5H, m), 7.39 (1H, d, J = 7.8 Hz), 7.22-7.13 (3H, m), 4.05 (2H, t, J = 5.5 Hz), 3.44-3.38 (3H, m).; 13C-NMR (CDCl3) δ: 56.2, 58.3, 116.8 (d, J = 23.0 Hz), 122.3 (d, J = 12.5 Hz), 127.2 (d, J = 12.5 Hz), 128.4, 128.5 (dd, J = 10.1, 7.2 Hz), 128.3, 129.9 (d, J= 2.9 Hz), 130.8, 132.0 (d, J = 5.3 Hz), 132.1 (t, J = 104.5 Hz), 133.5 (d, J = 3.8 Hz), 136.7, 138.1, 141.4, 141.4, 149.6, 155.0, 158.2, 160.7. (E) -2-fluoro-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C2) 1 H-NMR (CDCl 3 ) δ: 8.60 (1H, dd, J = 5.0, 0.9 Hz), 8.01 (2H, dt, J = 8.7, 1.8 Hz), 7.77 (2H, dd, J = 8.2, 1.4 Hz), 7.71-7.44 (5H, m) , 7.39 (1H, d, J = 7.8 Hz), 7.22-7.13 (3H, m), 4.05 (2H, t, J = 5.5 Hz), 3.44-3.38 (3H, m) .; 13 C-NMR (CDCl) 3 ) δ: 56.2, 58.3, 116.8 (d, J = 23.0 Hz), 122.3 (d, J = 12.5 Hz), 127.2 (d, J = 12.5 Hz), 128.4, 128.5 (dd, J = 10.1, 7.2 Hz) ), 128.3, 129.9 (d, J = 2.9 Hz), 130.8, 132.0 (d, J = 5.3 Hz), 132.1 (t, J = 104.5 Hz), 133.5 (d, J = 3.8 Hz), 136.7, 138.1, 141.4, 141.4, 149.6, 155.0, 158.2, 160.7.

(E)-4'-(2-hydroxyethanesulfonyl)-3-(6-methylpyridin-2-yl-2-vinyl)-1,1'-biphenyl (C3) 1H-NMR (CDCl3) δ: 8.00 (2H, dd, J = 6.6, 2.1 Hz), 7.80 (3H, td, J = 4.2, 2.3 Hz), 7.66-7.56 (3H, m), 7.50 (2H, dt, J = 8.4, 4.1 Hz), 7.28-7.23 (2H, m), 7.05 (1H, d, J = 7.8 Hz), 4.05 (2H, t, J = 5.5 Hz), 3.43-3.40 (2H, m), 2.59 (3H, s).; 13C-NMR (CDCl3) δ: 24.6, 56.3, 58.3, 118.9, 122.0, 126.0, 127.0, 127.2, 128.0, 128.5, 129.2, 129.4, 131.6, 136.8, 137.5, 137.6, 139.3, 146.7, 154.6, 158.3. (E) -4'-(2-hydroxyethanesulfonyl) -3- (6-methylpyridin-2-yl-2-vinyl) -1,1'-biphenyl (C3) 1 H-NMR (CDCl 3 ) δ: 8.00 ( 2H, dd, J = 6.6, 2.1 Hz), 7.80 (3H, td, J = 4.2, 2.3 Hz), 7.66-7.56 (3H, m), 7.50 (2H, dt, J = 8.4, 4.1 Hz), 7.28 -7.23 (2H, m), 7.05 (1H, d, J = 7.8 Hz), 4.05 (2H, t, J = 5.5 Hz), 3.43-3.40 (2H, m), 2.59 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 24.6, 56.3, 58.3, 118.9, 122.0, 126.0, 127.0, 127.2, 128.0, 128.5, 129.2, 129.4, 131.6, 136.8, 137.5, 137.6, 139.3, 146.7, 154.6, 158.3.

(E)-2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(6-methylpyridin-2-yl-2-vinyl)-1,1'-biphenyl (C4) 1H-NMR (CDCl3) δ: 8.01 (2H, dt, J = 8.9, 1.9 Hz), 7.78 (2H, dd, J = 8.5, 1.6 Hz), 7.64 (1H, dd, J = 7.3, 2.3 Hz), 7.58 (3H, tt, J = 10.1, 3.3 Hz), 7.20 (3H, tt, J = 16.7, 8.2 Hz), 7.04 (1H, d, J = 7.8 Hz), 4.05 (2H, dd, J = 6.9, 4.1 Hz), 3.43-3.41 (2H, m), 2.99 (1H, s), 2.58 (3H, s).; 13C-NMR (CDCl3) δ: 24.5, 56.2, 58.3, 116.8 (d, J = 23.0 Hz), 118.9, 122.0, 127.0, 128.1, 128.8 (t, J = 1.9 Hz), 129.1 (d, J = 3.8 Hz), 129.9 (d, J = 2.9 Hz), 130.4, 133.7 (d, J = 3.8 Hz), 136.8, 138.0, 141.4, 154.5, 158.1, 158.3, 160.6.; 19F-NMR (CDCl3) δ: -17.8. (E) -2-fluoro-4'-(2-hydroxyethanesulfonyl) -5- (6-methylpyridin-2-yl-2-vinyl) -1,1'-biphenyl (C4) 1 H-NMR (CDCl 3 ) δ: 8.01 (2H, dt, J = 8.9, 1.9 Hz), 7.78 (2H, dd, J = 8.5, 1.6 Hz), 7.64 (1H, dd, J = 7.3, 2.3 Hz), 7.58 (3H, tt, J = 10.1, 3.3 Hz), 7.20 (3H, tt, J = 16.7, 8.2 Hz), 7.04 (1H, d, J = 7.8 Hz), 4.05 (2H, dd, J = 6.9, 4.1 Hz), 3.43- 3.41 (2H, m), 2.99 (1H, s), 2.58 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 24.5, 56.2, 58.3, 116.8 (d, J = 23.0 Hz), 118.9, 122.0, 127.0, 128.1, 128.8 (t, J = 1.9 Hz), 129.1 (d, J = 3.8 Hz), 129.9 (d, J = 2.9 Hz), 130.4, 133.7 (d, J = 3.8 Hz), 136.8, 138.0, 141.4, 154.5, 158.1, 158.3, 160.6 .; 19 F-NMR (CDCl 3 ) δ: -17.8.

(E)-3-tert-butyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C5) 1H-NMR (CDCl3) δ: 8.62 (1H, d, J= 3.7 Hz), 8.02 (2H, dd, J = 6.9, 1.8 Hz), 7.83-7.80 (2H, m), 7.70 (3H, ddd, J = 12.6, 5.7, 3.9 Hz), 7.64 (1H, s), 7.54 (1H, t, J = 1.6 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.26 (1H, t, J = 8.0 Hz), 7.19-7.16 (1H, m), 4.05 (2H, s), 3.43-3.40 (2H, m), 2.93 (1H, s), 1.41 (9H, s).; 13C-NMR (CDCl3) δ: 31.3, 34.9, 56.4, 58.4, 122.0, 122.2, 123.2, 124.6, 124.9, 127.9, 128.2, 128.5, 129.4, 132.6, 136.6, 137.2, 137.4, 139.3, 147.5, 149.7, 152.6, 155.4. (E) -3-tert-butyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C5) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, d, J = 3.7 Hz), 8.02 (2H, dd, J = 6.9, 1.8 Hz), 7.83-7.80 (2H, m), 7.70 (3H, ddd, J = 12.6, 5.7, 3.9) Hz), 7.64 (1H, s), 7.54 (1H, t, J = 1.6 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.26 (1H, t, J = 8.0 Hz), 7.19-7.16 ( 1H, m), 4.05 (2H, s), 3.43-3.40 (2H, m), 2.93 (1H, s), 1.41 (9H, s) .; 13 C-NMR (CDCl 3 ) δ: 31.3, 34.9, 56.4, 58.4, 122.0, 122.2, 123.2, 124.6, 124.9, 127.9, 128.2, 128.5, 129.4, 132.6, 136.6, 137.2, 137.4, 139.3, 147.5, 149.7, 152.6, 155.4.

(E)-4'-(2-hydroxyethanesulfonyl)-3-methyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C6) 1H-NMR (CDCl3) δ: 8.60 (1H, d, J= 3.7 Hz), 7.98 (2H, dd, J = 6.9, 1.8 Hz), 7.77 (2H, t, J = 4.4 Hz), 7.70-7.62 (2H, m), 7.58 (1H, s), 7.42 (2H, t, J = 9.6 Hz), 7.33 (1H, s), 7.24 (1H, t, J = 13.5 Hz), 7.17 (1H, td, J = 6.2, 1.1 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.41 (3H, t, J = 5.5 Hz), 2.44 (3H, s).; 13C-NMR (CDCl3) δ: 21.4, 56.2, 58.3, 122.1, 122.2, 123.4, 127.9, 128.1, 128.4, 128.4, 128.5, 131.9, 132.0, 132.1, 136.6, 137.3, 137.5, 139.1, 139.4, 146.7, 149.5, 155.2. (E) -4'-(2-hydroxyethanesulfonyl) -3-methyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C6) 1 H-NMR (CDCl 3 ) δ: 8.60 (1H, d, J = 3.7 Hz), 7.98 (2H, dd, J = 6.9, 1.8 Hz), 7.77 (2H, t, J = 4.4 Hz), 7.70-7.62 (2H, m), 7.58 (1H) , s), 7.42 (2H, t, J = 9.6 Hz), 7.33 (1H, s), 7.24 (1H, t, J = 13.5 Hz), 7.17 (1H, td, J = 6.2, 1.1 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.41 (3H, t, J = 5.5 Hz), 2.44 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 21.4, 56.2, 58.3, 122.1, 122.2 , 123.4, 127.9, 128.1, 128.4, 128.4, 128.5, 131.9, 132.0, 132.1, 136.6, 137.3, 137.5, 139.1, 139.4, 146.7, 149.5, 155.2.

(E)-4'-(2-hydroxyethanesulfonyl)-3-(pyridin-2-yl-2-vinyl)-5-trifluoromethyl-1,1'-biphenyl (C7) 1H-NMR (CDCl3) δ: 8.63 (1H, dd, J= 5.0, 0.9 Hz), 8.05 (2H, dt, J = 8.7, 1.8 Hz), 7.91 (2H, d, J = 28.9 Hz), 7.82 (2H, dt, J = 8.5, 2.1 Hz), 7.72 (3H, dd, J = 8.9, 7.1 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.30 (1H, t, J = 10.1 Hz), 7.22 (1H, ddd, J = 7.6, 4.8, 0.9 Hz), 4.07 (2H, t, J = 4.8 Hz), 3.45-3.42 (2H, m), 3.21 (1H, s).; 13C-NMR (CDCl3) δ: 56.2, 58.4, 122.7 (d, J= 19.2 Hz), 123.5, 124.3 (d, J = 5.8 Hz), 125.1, 128.2, 128.7, 129.0 (d, J = 29.7 Hz), 130.5 (d, J = 1.9 Hz), 132.0 (q, J = 32.3 Hz), 136.4 (t, J = 253.5 Hz), 136.8, 138.5 (d, J = 6.7 Hz), 140.3, 142.3 (t, J = 205.6 Hz), 145.2, 149.7, 150.2, 154.5.; 19F-NMR (CDCl3) δ: 37.4. (E) -4'-(2-hydroxyethanesulfonyl) -3- (pyridin-2-yl-2-vinyl) -5-trifluoromethyl-1,1'-biphenyl (C7) 1 H-NMR (CDCl 3 ) δ: 8.63 (1H, dd, J = 5.0, 0.9 Hz), 8.05 (2H, dt, J = 8.7, 1.8 Hz), 7.91 (2H, d, J = 28.9 Hz), 7.82 (2H, dt, J = 8.5, 2.1 Hz), 7.72 (3H, dd, J = 8.9, 7.1 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.30 (1H, t, J = 10.1 Hz), 7.22 (1H, ddd, J = 7.6, 4.8, 0.9 Hz), 4.07 (2H, t, J = 4.8 Hz), 3.45-3.42 (2H, m), 3.21 (1H, s) .; 13 C-NMR (CDCl 3 ) δ: 56.2, 58.4 , 122.7 (d, J = 19.2 Hz), 123.5, 124.3 (d, J = 5.8 Hz), 125.1, 128.2, 128.7, 129.0 (d, J = 29.7 Hz), 130.5 (d, J = 1.9 Hz), 132.0 (q, J = 32.3 Hz), 136.4 (t, J = 253.5 Hz), 136.8, 138.5 (d, J = 6.7 Hz), 140.3, 142.3 (t, J = 205.6 Hz), 145.2, 149.7, 150.2, 154.5 .; 19 F-NMR (CDCl 3 ) δ: 37.4.

(E)-4'-(2-hydroxyethanesulfonyl)-4-methyl-3-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C8) 1H-NMR (CDCl3) δ: 8.61 (1H, t, J= 2.5 Hz), 7.98 (2H, dt, J = 8.4, 1.9 Hz), 7.90 (2H, dd, J = 13.1, 8.9 Hz), 7.80 (2H, dt, J = 8.7, 1.8 Hz), 7.69 (1H, td, J = 7.6, 1.8 Hz), 7.45-7.41 (2H, m), 7.30 (1H, d, J = 7.8 Hz), 7.16 (2H, tt, J = 6.2, 3.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.42-3.39 (2H, m), 3.33 (1H, s), 2.52 (3H, s).; 13C-NMR (CDCl3) δ: 19.7, 56.3, 58.3, 122.2, 122.3, 124.6, 126.9, 127.8, 128.4, 129.9, 130.0, 131.3, 131.9, 136.4, 136.6, 136.8, 137.2, 137.3, 146.7, 149.6, 155.3. (E) -4'-(2-hydroxyethanesulfonyl) -4-methyl-3- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C8) 1 H-NMR (CDCl 3 ) δ: 8.61 (1H, t, J = 2.5 Hz), 7.98 (2H, dt, J = 8.4, 1.9 Hz), 7.90 (2H, dd, J = 13.1, 8.9 Hz), 7.80 (2H, dt, J = 8.7, 1.8 Hz), 7.69 (1H, td, J = 7.6, 1.8 Hz), 7.45-7.41 (2H, m), 7.30 (1H, d, J = 7.8 Hz), 7.16 (2H, tt, J = 6.2, 3.8) Hz), 4.04 (2H, t, J = 5.5 Hz), 3.42-3.39 (2H, m), 3.33 (1H, s), 2.52 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 19.7 , 56.3, 58.3, 122.2, 122.3, 124.6, 126.9, 127.8, 128.4, 129.9, 130.0, 131.3, 131.9, 136.4, 136.6, 136.8, 137.2, 137.3, 146.7, 149.6, 155.3.

(E)-4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl-2-vinyl)-1,1'-biphenyl (C9) 1H-NMR (CDCl3) δ: 8.48 (1H, d, J = 4.6 Hz), 8.01 (2H, d, J = 8.7 Hz), 7.83 (4H, dt, J = 14.8, 7.1 Hz), 7.68 (1H, t, J = 3.7 Hz), 7.51 (3H, tt, J = 11.4, 2.7 Hz), 7.42 (1H, d, J = 15.6 Hz), 7.11 (1H, dd, J = 7.6, 4.8 Hz), 4.05 (2H, t, J = 5.5 Hz), 3.42-3.40 (2H, m), 3.01 (1H, s), 2.47 (3H, s).; 13C-NMR (CDCl3) δ: 18.9, 56.4, 58.4, 122.4, 125.0, 126.3, 127.2, 127.3, 128.1, 128.5, 129.5, 131.0, 132.9, 137.6, 138.0, 138.3, 139.5, 146.9, 147.1, 153.1. (E) -4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl-2-vinyl) -1,1'-biphenyl (C9) 1 H-NMR (CDCl 3 ) δ: 8.48 ( 1H, d, J = 4.6 Hz), 8.01 (2H, d, J = 8.7 Hz), 7.83 (4H, dt, J = 14.8, 7.1 Hz), 7.68 (1H, t, J = 3.7 Hz), 7.51 ( 3H, tt, J = 11.4, 2.7 Hz), 7.42 (1H, d, J = 15.6 Hz), 7.11 (1H, dd, J = 7.6, 4.8 Hz), 4.05 (2H, t, J = 5.5 Hz), 3.42-3.40 (2H, m), 3.01 (1H, s), 2.47 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 18.9, 56.4, 58.4, 122.4, 125.0, 126.3, 127.2, 127.3, 128.1, 128.5, 129.5, 131.0, 132.9, 137.6, 138.0, 138.3, 139.5, 146.9, 147.1, 153.1.

(E)-4'-(2-hydroxyethanesulfonyl)-3-(6-methylpyridin-2-yl-2-vinyl)-4-methyl-1,1'-biphenyl (C10) 1H-NMR (CDCl3) δ: 7.99 (2H, dt, J = 8.7, 2.1 Hz), 7.89 (1H, d, J = 2.3 Hz), 7.86-7.80 (3H, m), 7.58 (1H, t, J = 7.8 Hz), 7.45 (1H, dd, J= 7.8, 2.3 Hz), 7.30 (2H, t, J = 8.5 Hz), 7.16 (1H, d, J = 16.0 Hz), 7.05 (1H, d, J = 7.3 Hz), 4.06-4.03 (2H, m), 3.42-3.39 (2H, m), 2.95 (1H, s), 2.60 (3H, s), 2.53 (3H, s).; 13C-NMR (CDCl3) δ: 19.7, 24.6, 56.4, 58.4, 118.8, 122.0, 124.7, 126.8, 127.8, 128.5, 129.5, 130.6, 131.3, 136.7, 136.7, 136.9, 137.2, 146.9, 155.0, 158.4. (E) -4'-(2-hydroxyethanesulfonyl) -3- (6-methylpyridin-2-yl-2-vinyl) -4-methyl-1,1'-biphenyl (C10) 1 H-NMR (CDCl 3 ) δ: 7.99 (2H, dt, J = 8.7, 2.1 Hz), 7.89 (1H, d, J = 2.3 Hz), 7.86-7.80 (3H, m), 7.58 (1H, t, J = 7.8 Hz), 7.45 (1H, dd, J = 7.8, 2.3 Hz), 7.30 (2H, t, J = 8.5 Hz), 7.16 (1H, d, J = 16.0 Hz), 7.05 (1H, d, J = 7.3 Hz), 4.06 -4.03 (2H, m), 3.42-3.39 (2H, m), 2.95 (1H, s), 2.60 (3H, s), 2.53 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 19.7 , 24.6, 56.4, 58.4, 118.8, 122.0, 124.7, 126.8, 127.8, 128.5, 129.5, 130.6, 131.3, 136.7, 136.7, 136.9, 137.2, 146.9, 155.0, 158.4.

(E)-4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl-2-vinyl)-4-methyl-1,1'-biphenyl (C11) 1H-NMR (CDCl3) δ: 8.48 (1H, dd, J = 4.8, 1.6 Hz), 8.05 (1H, d, J = 15.1 Hz), 8.00 (2H, dt, J = 8.7, 1.8 Hz), 7.84 (1H, d, J = 1.8 Hz), 7.81 (2H, dt, J = 8.5, 1.9 Hz), 7.46 (3H, tt, J = 10.1, 2.9 Hz), 7.32 (2H, d, J = 7.3 Hz), 7.27 (1H, d, J = 2.3 Hz), 7.11 (1H, dd, J = 7.8, 4.6 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.41-3.39 (2H, m), 3.10 (1H, s), 2.54 (3H, s), 2.45 (3H, s).; 13C-NMR (CDCl3) δ: 18.9, 19.8, 56.3, 58.4, 122.3, 124.8, 126.4, 126.8, 127.9, 128.5, 128.6, 131.0, 131.1, 131.3, 132.0, 136.9, 137.2, 137.2, 137.6, 138.3, 146.9, 147.1, 153.3. (E) -4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl-2-vinyl) -4-methyl-1,1'-biphenyl (C11) 1 H-NMR (CDCl 3 ) δ: 8.48 (1H, dd, J = 4.8, 1.6 Hz), 8.05 (1H, d, J = 15.1 Hz), 8.00 (2H, dt, J = 8.7, 1.8 Hz), 7.84 (1H, d, J = 1.8 Hz), 7.81 (2H, dt, J = 8.5, 1.9 Hz), 7.46 (3H, tt, J = 10.1, 2.9 Hz), 7.32 (2H, d, J = 7.3 Hz), 7.27 (1H, d, J = 2.3 Hz), 7.11 (1H, dd, J = 7.8, 4.6 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.41-3.39 (2H, m), 3.10 (1H, s), 2.54 ( 3H, s), 2.45 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 18.9, 19.8, 56.3, 58.4, 122.3, 124.8, 126.4, 126.8, 127.9, 128.5, 128.6, 131.0, 131.1, 131.3 , 132.0, 136.9, 137.2, 137.2, 137.6, 138.3, 146.9, 147.1, 153.3.

(E)-4'-(2-hydroxyethanesulfonyl)-2-methyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C12) 1H-NMR (CDCl3) δ: 8.58 (1H, t, J= 2.5 Hz), 7.99 (2H, d, J = 8.1 Hz), 7.64 (2H, ddd, J = 16.8, 8.9, 5.5 Hz), 7.57-7.52 (3H, m), 7.42 (1H, d, J = 1.6 Hz), 7.38 (1H, d, J= 8.1 Hz), 7.31 (1H, d, J = 7.9 Hz), 7.16 (2H, dt, J = 10.4, 3.9 Hz), 4.07 (2H, t, J = 5.6 Hz), 3.45-3.43 (2H, m), 3.29 (1H, br s), 2.26 (3H, s).; 13C-NMR (CDCl3) δ: 20.2, 56.3, 58.3, 122.1, 122.1, 126.9, 127.7, 127.9, 128.0, 130.2, 131.9, 131.9, 132.0, 134.6, 135.4, 136.6, 137.4, 140.1, 147.7, 149.5, 153.3. (E) -4'-(2-hydroxyethanesulfonyl) -2-methyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C12) 1 H-NMR (CDCl 3 ) δ: 8.58 (1H, t, J = 2.5 Hz), 7.99 (2H, d, J = 8.1 Hz), 7.64 (2H, ddd, J = 16.8, 8.9, 5.5 Hz), 7.57-7.52 (3H, m), 7.42 (1H, d, J = 1.6 Hz), 7.38 (1H, d, J = 8.1 Hz), 7.31 (1H, d, J = 7.9 Hz), 7.16 (2H, dt, J = 10.4, 3.9 Hz), 4.07 (2H, t, J = 5.6 Hz), 3.45-3.43 (2H, m), 3.29 (1H, br s), 2.26 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 20.2, 56.3, 58.3, 122.1, 122.1, 126.9, 127.7, 127.9, 128.0, 130.2, 131.9, 131.9, 132.0, 134.6, 135.4, 136.6, 137.4, 140.1, 147.7, 149.5, 153.3.

(E)-4'-(2-hydroxyethanesulfonyl)-4-propyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C14) 1H-NMR (CDCl3) δ: 8.62 (1H, dd, J= 4.8, 0.9 Hz), 8.00-7.97 (2H, m), 7.94 (1H, d, J = 15.9 Hz), 7.89 (1H, d, J = 2.0 Hz), 7.81 (2H, dd, J = 6.8, 2.0 Hz), 7.70 (1H, td, J= 7.7, 1.8 Hz), 7.46 (3H, dt, J = 15.8, 6.4 Hz), 7.31 (1H, d, J = 7.9 Hz), 7.20-7.13 (2H, m), 4.04 (2H, t, J = 5.6 Hz), 3.42-3.40 (2H, m), 3.29 (1H, s), 2.83 (2H, t, J = 7.7 Hz), 1.69 (2H, dd, J = 15.2, 7.5 Hz), 1.01 (3H, t, J = 7.3 Hz).; 13C-NMR (CDCl3) δ: 14.0, 24.2, 35.1, 56.3, 58.3, 122.1, 122.3, 124.9, 126.9, 127.8, 128.4, 128.5, 129.9, 130.1, 130.6, 132.0, 136.1, 136.6, 136.8, 137.2, 141.9, 146.7, 149.6, 155.4. (E) -4'-(2-hydroxyethanesulfonyl) -4-propyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C14) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, dd, J = 4.8, 0.9 Hz), 8.00-7.97 (2H, m), 7.94 (1H, d, J = 15.9 Hz), 7.89 (1H, d, J = 2.0 Hz), 7.81 (2H) , dd, J = 6.8, 2.0 Hz), 7.70 (1H, td, J = 7.7, 1.8 Hz), 7.46 (3H, dt, J = 15.8, 6.4 Hz), 7.31 (1H, d, J = 7.9 Hz) , 7.20-7.13 (2H, m), 4.04 (2H, t, J = 5.6 Hz), 3.42-3.40 (2H, m), 3.29 (1H, s), 2.83 (2H, t, J = 7.7 Hz), 1.69 (2H, dd, J = 15.2, 7.5 Hz), 1.01 (3H, t, J = 7.3 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 24.2, 35.1, 56.3, 58.3, 122.1, 122.3 , 124.9, 126.9, 127.8, 128.4, 128.5, 129.9, 130.1, 130.6, 132.0, 136.1, 136.6, 136.8, 137.2, 141.9, 146.7, 149.6, 155.4.

(E)-4-ethoxy-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C15) 1H-NMR (CDCl3) δ: 8.61 (1H, t, J= 2.4 Hz), 7.98-7.92 (3H, m), 7.88 (1H, d, J = 2.3 Hz), 7.78 (2H, dt, J= 8.6, 2.0 Hz), 7.68 (1H, td, J = 7.7, 1.8 Hz), 7.51 (1H, dd, J = 8.6, 2.5 Hz), 7.47 (1H, d, J = 8.0 Hz), 7.35 (1H, d, J = 16.2 Hz), 7.16 (1H, ddd, J = 7.5, 4.8, 1.1 Hz), 7.01 (1H, d, J = 8.6 Hz), 4.20 (2H, q, J = 7.0 Hz), 4.05 (2H, t, J = 5.4 Hz), 3.40 (2H, td, J = 4.1, 2.1 Hz), 2.97 (1H, br s), 1.54 (3H, t, J = 7.0 Hz).; 13C-NMR (CDCl3) δ: 14.8, 56.4, 58.4, 64.2, 112.4, 121.8, 122.0, 126.4, 126.5, 127.4, 127.5, 128.2, 128.5, 129.6, 131.1, 136.5, 136.7, 146.6, 149.6, 156.0, 157.5. (E) -4-ethoxy-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C15) 1 H-NMR (CDCl 3 ) δ: 8.61 (1H, t, J = 2.4 Hz), 7.98-7.92 (3H, m), 7.88 (1H, d, J = 2.3 Hz), 7.78 (2H, dt, J = 8.6, 2.0 Hz), 7.68 (1H) , td, J = 7.7, 1.8 Hz), 7.51 (1H, dd, J = 8.6, 2.5 Hz), 7.47 (1H, d, J = 8.0 Hz), 7.35 (1H, d, J = 16.2 Hz), 7.16 (1H, ddd, J = 7.5, 4.8, 1.1 Hz), 7.01 (1H, d, J = 8.6 Hz), 4.20 (2H, q, J = 7.0 Hz), 4.05 (2H, t, J = 5.4 Hz) , 3.40 (2H, td, J = 4.1, 2.1 Hz), 2.97 (1H, br s), 1.54 (3H, t, J = 7.0 Hz).; 13 C-NMR (CDCl 3 ) δ: 14.8, 56.4, 58.4, 64.2, 112.4, 121.8, 122.0, 126.4, 126.5, 127.4, 127.5, 128.2, 128.5, 129.6, 131.1, 136.5, 136.7, 146.6, 149.6, 156.0, 157.5.

(E)-4'-(2-hydroxyethanesulfonyl)-4-pentyl-3-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C16) 1H-NMR (CDCl3) δ: 8.62 (1H, d, J= 4.1 Hz), 7.99 (2H, d, J = 8.7 Hz), 7.93 (1H, d, J = 15.6 Hz), 7.88 (1H, d, J = 1.8 Hz), 7.81 (2H, d, J = 8.7 Hz), 7.69 (1H, td, J = 7.8, 1.8 Hz), 7.48 (1H, dd, J = 7.8, 1.8 Hz), 7.43 (1H, d, J= 8.2 Hz), 7.31 (1H, d, J = 8.2 Hz), 7.16 (2H, dd, J = 13.7, 9.2 Hz), 4.04 (2H, d, J = 5.5 Hz), 3.41 (2H, t, J = 5.5 Hz), 3.18 (1H, s), 2.84 (2H, t, J = 7.8 Hz), 1.65 (2H, dd, J = 15.1, 7.3 Hz), 1.38 (4H, t, J = 3.7 Hz), 0.90 (3H, t, J = 7.1 Hz).; 13C-NMR (CDCl3) δ: 14.0, 22.4, 30.7, 31.6, 33.0, 56.3, 58.4, 122.0, 122.2, 125.0, 126.9, 127.8, 128.5, 129.9, 130.2, 130.5, 136.1, 136.6, 136.8, 137.2, 142.1, 146.8, 149.7, 155.5. (E) -4'-(2-hydroxyethanesulfonyl) -4-pentyl-3- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C16) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, d, J = 4.1 Hz), 7.99 (2H, d, J = 8.7 Hz), 7.93 (1H, d, J = 15.6 Hz), 7.88 (1H, d, J = 1.8 Hz), 7.81 ( 2H, d, J = 8.7 Hz), 7.69 (1H, td, J = 7.8, 1.8 Hz), 7.48 (1H, dd, J = 7.8, 1.8 Hz), 7.43 (1H, d, J = 8.2 Hz), 7.31 (1H, d, J = 8.2 Hz), 7.16 (2H, dd, J = 13.7, 9.2 Hz), 4.04 (2H, d, J = 5.5 Hz), 3.41 (2H, t, J = 5.5 Hz), 3.18 (1H, s), 2.84 (2H, t, J = 7.8 Hz), 1.65 (2H, dd, J = 15.1, 7.3 Hz), 1.38 (4H, t, J = 3.7 Hz), 0.90 (3H, t) , J = 7.1 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 22.4, 30.7, 31.6, 33.0, 56.3, 58.4, 122.0, 122.2, 125.0, 126.9, 127.8, 128.5, 129.9, 130.2, 130.5, 136.1, 136.6, 136.8, 137.2, 142.1, 146.8, 149.7, 155.5.

(E)-4'-(2-hydroxyethanesulfonyl)-4-iso-propyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C17) 1H-NMR (CDCl3) δ: 8.62 (1H, d, J= 3.7 Hz), 8.06 (1H, d, J = 16.0 Hz), 7.99 (2H, d, J = 8.7 Hz), 7.83 (3H, dd, J = 11.4, 5.0 Hz), 7.69 (1H, td, J = 7.7, 1.7 Hz), 7.54 (1H, dd, J = 8.0, 2.1 Hz), 7.43 (2H, t, J = 8.2 Hz), 7.18 (1H, dd, J = 7.1, 5.3 Hz), 7.11 (1H, d, J = 15.6 Hz), 4.05 (2H, t, J = 5.3 Hz), 3.51-3.44 (1H, m), 3.41 (2H, dd, J = 6.9, 4.1 Hz), 3.16 (1H, s), 1.32 (6H, d, J = 6.4 Hz).; 13C-NMR (CDCl3) δ: 23.5, 29.1, 56.3, 58.4, 122.3, 122.3, 125.4, 126.1, 127.3, 127.8, 128.5, 130.0, 130.7, 135.8, 136.5, 136.6, 137.2, 146.7, 147.7, 149.7, 155.4. (E) -4'-(2-hydroxyethanesulfonyl) -4-iso-propyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C17) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, d, J = 3.7 Hz), 8.06 (1H, d, J = 16.0 Hz), 7.99 (2H, d, J = 8.7 Hz), 7.83 (3H, dd, J = 11.4, 5.0 Hz) ), 7.69 (1H, td, J = 7.7, 1.7 Hz), 7.54 (1H, dd, J = 8.0, 2.1 Hz), 7.43 (2H, t, J = 8.2 Hz), 7.18 (1H, dd, J = 7.1, 5.3 Hz), 7.11 (1H, d, J = 15.6 Hz), 4.05 (2H, t, J = 5.3 Hz), 3.51-3.44 (1H, m), 3.41 (2H, dd, J = 6.9, 4.1) Hz), 3.16 (1H, s), 1.32 (6H, d, J = 6.4 Hz) .; 13 C-NMR (CDCl 3 ) δ: 23.5, 29.1, 56.3, 58.4, 122.3, 122.3, 125.4, 126.1, 127.3 , 127.8, 128.5, 130.0, 130.7, 135.8, 136.5, 136.6, 137.2, 146.7, 147.7, 149.7, 155.4.

(E)-4-iso-butyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C18) 1H-NMR (CDCl3) δ: 8.61 (1H, d, J= 4.1 Hz), 7.99 (2H, d, J = 8.2 Hz), 7.92 (2H, dd, J = 10.8, 8.9 Hz), 7.82 (2H, d, J = 8.7 Hz), 7.69 (1H, td, J = 7.6, 1.7 Hz), 7.47 (1H, dd, J = 7.8, 1.8 Hz), 7.43 (1H, d, J = 7.8 Hz), 7.27 (1H, t, J = 3.9 Hz), 7.19-7.13 (2H, m), 4.04 (2H, t, J = 5.3 Hz), 3.41 (2H, t, J = 5.5 Hz), 3.21 (1H, s), 2.72 (2H, d, J = 7.3 Hz), 1.98-1.91 (1H, m), 0.97 (6H, d, J = 6.4 Hz).; 13C-NMR (CDCl3) δ: 22.5, 30.0, 42.3, 56.3, 58.4, 121.9, 122.2, 125.0, 126.6, 127.8, 128.5, 130.1, 130.2, 131.5, 136.4, 136.6, 136.8, 137.3, 141.0, 146.7, 149.7, 155.5. (E) -4-iso-butyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C18) 1 H-NMR (CDCl 3 ) δ: 8.61 (1H, d, J = 4.1 Hz), 7.99 (2H, d, J = 8.2 Hz), 7.92 (2H, dd, J = 10.8, 8.9 Hz), 7.82 (2H, d, J = 8.7 Hz) ), 7.69 (1H, td, J = 7.6, 1.7 Hz), 7.47 (1H, dd, J = 7.8, 1.8 Hz), 7.43 (1H, d, J = 7.8 Hz), 7.27 (1H, t, J = 3.9 Hz), 7.19-7.13 (2H, m), 4.04 (2H, t, J = 5.3 Hz), 3.41 (2H, t, J = 5.5 Hz), 3.21 (1H, s), 2.72 (2H, d, J = 7.3 Hz), 1.98-1.91 (1H, m), 0.97 (6H, d, J = 6.4 Hz) .; 13 C-NMR (CDCl 3 ) δ: 22.5, 30.0, 42.3, 56.3, 58.4, 121.9, 122.2, 125.0, 126.6, 127.8, 128.5, 130.1, 130.2, 131.5, 136.4, 136.6, 136.8, 137.3, 141.0, 146.7, 149.7, 155.5.

(E)-4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl-2-vinyl)-4-propyl-1,1'-biphenyl (C19) 1H-NMR (CDCl3) δ: 8.48 (1H, dd, J = 4.7, 1.6 Hz), 8.08 (1H, d, J = 15.6 Hz), 8.00 (2H, dt, J = 8.6, 2.0 Hz), 7.82 (3H, dq, J = 10.0, 2.5 Hz), 7.49-7.47 (2H, m), 7.33-7.25 (3H, m), 7.11 (1H, dd, J = 7.6, 4.8 Hz), 4.05-4.03 (2H, m), 3.40 (2H, dt, J = 5.8, 2.5 Hz), 3.08 (1H, s), 2.84 (2H, t, J = 7.7 Hz), 2.45 (3H, s), 1.70 (2H, dd, J = 15.3, 7.4 Hz), 1.01 (3H, t, J = 7.3 Hz).; 13C-NMR (CDCl3) δ: 13.9, 18.9, 24.0, 35.0, 56.1, 58.3, 122.2, 125.0, 126.4, 126.8, 127.7, 128.4, 130.4, 130.9, 131.1, 136.7, 136.7, 137.2, 138.3, 142.0, 146.7, 147.0, 153.3. (E) -4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl-2-vinyl) -4-propyl-1,1'-biphenyl (C19) 1 H-NMR (CDCl 3 ) δ: 8.48 (1H, dd, J = 4.7, 1.6 Hz), 8.08 (1H, d, J = 15.6 Hz), 8.00 (2H, dt, J = 8.6, 2.0 Hz), 7.82 (3H, dq, J = 10.0, 2.5 Hz), 7.49-7.47 (2H, m), 7.33-7.25 (3H, m), 7.11 (1H, dd, J = 7.6, 4.8 Hz), 4.05-4.03 (2H, m), 3.40 (2H) , dt, J = 5.8, 2.5 Hz), 3.08 (1H, s), 2.84 (2H, t, J = 7.7 Hz), 2.45 (3H, s), 1.70 (2H, dd, J = 15.3, 7.4 Hz) , 1.01 (3H, t, J = 7.3 Hz) .; 13 C-NMR (CDCl 3 ) δ: 13.9, 18.9, 24.0, 35.0, 56.1, 58.3, 122.2, 125.0, 126.4, 126.8, 127.7, 128.4, 130.4, 130.9, 131.1, 136.7, 136.7, 137.2, 138.3, 142.0, 146.7, 147.0, 153.3.

(E)-4'-(2-hydroxyethanesulfonyl)-3-(3-penthylpyridin-2-yl-2-vinyl)-4-propyl-1,1'-biphenyl (C21) 1H-NMR (CDCl3) δ: 8.49 (1H, dd, J = 4.8, 1.7 Hz), 8.09 (1H, d, J = 15.4 Hz), 8.00 (2H, dt, J = 8.6, 2.0 Hz), 7.84-7.80 (3H, m), 7.48 (2H, dt, J = 7.8, 2.0 Hz), 7.33 (2H, t, J = 4.6 Hz), 7.27 (1H, d, J= 4.6 Hz), 7.13 (1H, dd, J = 7.7, 4.7 Hz), 4.06-4.04 (2H, m), 3.42-3.39 (2H, m), 3.08 (1H, s), 2.84 (2H, t, J = 7.7 Hz), 2.75 (2H, t, J = 7.8 Hz), 1.75-1.60 (4H, m), 1.40-1.34 (4H, m), 1.01 (3H, t, J = 7.3 Hz), 0.90-0.87 (3H, m).; 13C-NMR (CDCl3) δ: 14.0, 14.0, 22.4, 24.1, 30.5, 31.5, 32.3, 35.1, 56.3, 58.4, 122.3, 125.2, 126.6, 126.8, 127.8, 128.5, 130.5, 131.2, 135.6, 136.8, 137.1, 137.2, 137.5, 142.1, 147.0, 147.2, 152.9. (E) -4'-(2-hydroxyethanesulfonyl) -3- (3-penthylpyridin-2-yl-2-vinyl) -4-propyl-1,1'-biphenyl (C21) 1 H-NMR (CDCl 3 ) δ: 8.49 (1H, dd, J = 4.8, 1.7 Hz), 8.09 (1H, d, J = 15.4 Hz), 8.00 (2H, dt, J = 8.6, 2.0 Hz), 7.84-7.80 (3H, m) , 7.48 (2H, dt, J = 7.8, 2.0 Hz), 7.33 (2H, t, J = 4.6 Hz), 7.27 (1H, d, J = 4.6 Hz), 7.13 (1H, dd, J = 7.7, 4.7) Hz), 4.06-4.04 (2H, m), 3.42-3.39 (2H, m), 3.08 (1H, s), 2.84 (2H, t, J = 7.7 Hz), 2.75 (2H, t, J = 7.8 Hz) ), 1.75-1.60 (4H, m), 1.40-1.34 (4H, m), 1.01 (3H, t, J = 7.3 Hz), 0.90-0.87 (3H, m) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 14.0, 22.4, 24.1, 30.5, 31.5, 32.3, 35.1, 56.3, 58.4, 122.3, 125.2, 126.6, 126.8, 127.8, 128.5, 130.5, 131.2, 135.6, 136.8, 137.1, 137.2, 137.5, 142.1, 147.0, 147.2, 152.9.

(E)-4-heptyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C22) 1H-NMR (CDCl3) δ: 8.63-8.61 (1H, m), 8.00-7.98 (2H, m), 7.94 (1H, d, J = 16.0 Hz), 7.89 (1H, d, J = 1.8 Hz), 7.82 (2H, dt, J = 8.5, 1.9 Hz), 7.70 (1H, td, J = 7.8, 1.8 Hz), 7.48 (1H, dd, J = 8.0, 2.1 Hz), 7.43 (1H, d, J = 7.8 Hz), 7.32 (1H, d, J = 8.2 Hz), 7.17 (2H, tt, J = 6.2, 3.7 Hz), 4.05 (2H, d, J = 4.6 Hz), 3.42-3.39 (2H, m), 3.14 (1H, s), 2.84 (2H, t, J= 7.8 Hz), 1.69-1.62 (2H, m), 1.44-1.22 (8H, m), 0.87 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 14.1, 22.6, 29.1, 29.4, 31.1, 31.7, 33.1, 56.3, 58.4, 122.0, 122.3, 125.0, 126.9, 127.8, 128.5, 129.9, 130.2, 130.5, 136.1, 136.6, 136.8, 137.2, 142.2, 146.8, 149.7, 155.5. (E) -4-heptyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C22) 1 H-NMR (CDCl 3 ) δ: 8.63-8.61 (1H, m), 8.00-7.98 (2H, m), 7.94 (1H, d, J = 16.0 Hz), 7.89 (1H, d, J = 1.8 Hz), 7.82 (2H, dt, J = 8.5, 1.9 Hz), 7.70 (1H, td, J = 7.8, 1.8 Hz), 7.48 (1H, dd, J = 8.0, 2.1 Hz), 7.43 (1H, d, J = 7.8 Hz), 7.32 (1H, d, J = 8.2 Hz), 7.17 (2H, tt, J = 6.2, 3.7 Hz), 4.05 (2H, d, J = 4.6 Hz), 3.42-3.39 (2H, m), 3.14 (1H, s), 2.84 (2H, t, J = 7.8 Hz), 1.69-1.62 (2H, m), 1.44-1.22 (8H, m), 0.87 (3H, t, J = 6.9 Hz).; 13 C-NMR (CDCl 3 ) ) δ: 14.1, 22.6, 29.1, 29.4, 31.1, 31.7, 33.1, 56.3, 58.4, 122.0, 122.3, 125.0, 126.9, 127.8, 128.5, 129.9, 130.2, 130.5, 136.1, 136.6, 136.8, 137.2, 142.2, 146.8 , 149.7, 155.5.

(E)-4'-(2-hydroxyethanesulfonyl)-4-octyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C23) 1H-NMR (CDCl3) δ: 8.62 (1H, dd, J= 5.0, 0.9 Hz), 7.99 (2H, t, J = 4.4 Hz), 7.93 (1H, d, J = 16.0 Hz), 7.89 (1H, d, J = 1.8 Hz), 7.81 (2H, dd, J = 8.7, 1.8 Hz), 7.69 (1H, td, J = 7.6, 1.8 Hz), 7.46 (2H, td, J = 10.1, 4.0 Hz), 7.31 (1H, d, J = 7.8 Hz), 7.20-7.14 (2H, m), 4.04 (2H, d, J = 3.7 Hz), 3.40 (2H, td, J = 6.5, 4.1 Hz), 3.27 (1H, s), 2.84 (2H, t, J = 7.8 Hz), 1.69-1.61 (2H, m), 1.44-1.26 (10H, m), 0.86 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 14.0, 22.6, 29.2, 29.3, 29.4, 31.0, 31.8, 33.0, 56.3, 58.3, 122.0, 122.2, 124.9, 126.0, 127.8, 128.5, 129.9, 130.2, 130.5, 136.0, 136.6, 136.7, 137.2, 142.1, 146.7, 149.6, 155.5. (E) -4'-(2-hydroxyethanesulfonyl) -4-octyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C23) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, dd, J = 5.0, 0.9 Hz), 7.99 (2H, t, J = 4.4 Hz), 7.93 (1H, d, J = 16.0 Hz), 7.89 (1H, d, J = 1.8 Hz), 7.81 (2H, dd, J = 8.7, 1.8 Hz), 7.69 (1H, td, J = 7.6, 1.8 Hz), 7.46 (2H, td, J = 10.1, 4.0 Hz), 7.31 (1H, d, J = 7.8 Hz), 7.20-7.14 (2H, m), 4.04 (2H, d, J = 3.7 Hz), 3.40 (2H, td, J = 6.5, 4.1 Hz), 3.27 (1H, s), 2.84 (2H, t, J = 7.8 Hz), 1.69-1.61 (2H, m), 1.44-1.26 (10H, m), 0.86 (3H, t, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0 , 22.6, 29.2, 29.3, 29.4, 31.0, 31.8, 33.0, 56.3, 58.3, 122.0, 122.2, 124.9, 126.0, 127.8, 128.5, 129.9, 130.2, 130.5, 136.0, 136.6, 136.7, 137.2, 142.1, 146.7, 149.6 , 155.5.

(E)-4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (C24) 1H-NMR (CDCl3) δ: 8.62 (1H, d, J= 4.1 Hz), 8.02 (1H, d, J = 16.0 Hz), 7.98 (2H, dt, J = 8.5, 2.1 Hz), 7.85 (1H, d, J = 2.3 Hz), 7.80 (2H, d, J = 8.2 Hz), 7.70 (1H, td, J = 7.6, 1.7 Hz), 7.52 (1H, dd, J = 8.2, 1.8 Hz), 7.42 (2H, t, J = 8.9 Hz), 7.19 (1H, dd, J = 7.1, 4.4 Hz), 7.11 (1H, d, J = 15.6 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41 (2H, t, J = 5.5 Hz), 3.34 (1H, s), 3.05-2.99 (1H, m), 1.89 (4H, t, J = 9.2 Hz), 1.80 (1H, d, J = 13.7 Hz), 1.49 (4H, t, J = 10.3 Hz), 1.34-1.25 (1H, m).; 13C-NMR (CDCl3) δ: 26.1, 26.8, 33.9, 39.7, 56.2, 58.3, 122.1, 122.3, 125.4, 126.7, 127.1, 127.8, 128.4, 130.1, 130.7, 135.8, 136.4, 136.7, 137.2, 146.7, 146.7, 149.6, 155.5. (E) -4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (C24) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, d, J = 4.1 Hz), 8.02 (1H, d, J = 16.0 Hz), 7.98 (2H, dt, J = 8.5, 2.1 Hz), 7.85 (1H, d, J = 2.3 Hz) ), 7.80 (2H, d, J = 8.2 Hz), 7.70 (1H, td, J = 7.6, 1.7 Hz), 7.52 (1H, dd, J = 8.2, 1.8 Hz), 7.42 (2H, t, J = 8.9 Hz), 7.19 (1H, dd, J = 7.1, 4.4 Hz), 7.11 (1H, d, J = 15.6 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41 (2H, t, J = 5.5 Hz), 3.34 (1H, s), 3.05-2.99 (1H, m), 1.89 (4H, t, J = 9.2 Hz), 1.80 (1H, d, J = 13.7 Hz), 1.49 (4H, t, J = 10.3 Hz), 1.34-1.25 (1H, m) .; 13 C-NMR (CDCl 3 ) δ: 26.1, 26.8, 33.9, 39.7, 56.2, 58.3, 122.1, 122.3, 125.4, 126.7, 127.1, 127.8, 128.4, 130.1, 130.7, 135.8, 136.4, 136.7, 137.2, 146.7, 146.7, 149.6, 155.5.

(E)-4'-(2-hydroxyethanesulfonyl)-4-cyclo-pentyl-5-(pyridin-2-ylethyl)-1,1'-biphenyl (C25) 1H-NMR (CDCl3) δ: 8.62 (1H, d, J= 3.9 Hz), 8.05 (1H, d, J = 15.8 Hz), 7.98 (2H, dt, J = 8.5, 1.8 Hz), 7.84 (1H, d, J = 2.1 Hz), 7.81 (2H, dt, J = 8.5, 1.8 Hz), 7.69 (1H, td, J = 7.7, 1.8 Hz), 7.52 (1H, dd, J = 8.1, 1.9 Hz), 7.43 (2H, dd, J = 8.0, 4.8 Hz), 7.18 (1H, ddd, J = 7.6, 4.8, 0.9 Hz), 7.10 (1H, d, J = 15.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.53-3.44 (1H, m), 3.42-3.39 (2H, m), 3.30 (1H, s), 2.12 (2H, dt, J = 15.3, 5.6 Hz), 1.89-1.61 (6H, m).; 13C-NMR (CDCl3) δ: 25.6, 34.2, 41.4, 56.3, 58.3, 122.3, 125.2, 126.7, 127.1, 127.8, 128.5, 130.4, 130.5, 136.4, 136.5, 136.7, 137.2, 145.5, 146.7, 149.6, 155.4. (E) -4'-(2-hydroxyethanesulfonyl) -4-cyclo-pentyl-5- (pyridin-2-ylethyl) -1,1'-biphenyl (C25) 1 H-NMR (CDCl 3 ) δ: 8.62 ( 1H, d, J = 3.9 Hz), 8.05 (1H, d, J = 15.8 Hz), 7.98 (2H, dt, J = 8.5, 1.8 Hz), 7.84 (1H, d, J = 2.1 Hz), 7.81 ( 2H, dt, J = 8.5, 1.8 Hz), 7.69 (1H, td, J = 7.7, 1.8 Hz), 7.52 (1H, dd, J = 8.1, 1.9 Hz), 7.43 (2H, dd, J = 8.0, 4.8 Hz), 7.18 (1H, ddd, J = 7.6, 4.8, 0.9 Hz), 7.10 (1H, d, J = 15.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.53-3.44 (1H, m), 3.42-3.39 (2H, m), 3.30 (1H, s), 2.12 (2H, dt, J = 15.3, 5.6 Hz), 1.89-1.61 (6H, m) .; 13 C-NMR (CDCl 3 ) ) δ: 25.6, 34.2, 41.4, 56.3, 58.3, 122.3, 125.2, 126.7, 127.1, 127.8, 128.5, 130.4, 130.5, 136.4, 136.5, 136.7, 137.2, 145.5, 146.7, 149.6, 155.4.

(4)Ｄ１～Ｄ２５の合成
Ｄ１～Ｄ２５の合成は下記合成法により合成した。 (4) Synthesis of D1 to D25 The synthesis of D1 to D25 was synthesized by the following synthesis method.

Figure 0007060775000163
Figure 0007060775000163

合成したD1～D25のNMRを下記に示す。 The synthesized NMR of D1 to D25 is shown below.

(Z)-4'-(2-hydroxyethanesulfonyl)-3-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D1) 1H-NMR (CDCl3) δ: 8.63 (1H, d, J= 4.5 Hz), 8.01 (2H, d, J = 7.9 Hz), 7.82 (3H, d, J = 8.5 Hz), 7.69 (3H, dt, J = 24.6, 8.2 Hz), 7.53 (2H, dd, J = 16.4, 7.4 Hz), 7.42 (1H, d, J = 7.9 Hz), 7.26 (1H, d, J = 15.9 Hz), 7.19 (1H, dd, J = 7.4, 4.5 Hz), 4.56 (2H, t, J = 6.2 Hz), 3.54 (2H, t, J= 6.2 Hz).; 13C-NMR (CDCl3) δ: 54.9, 57.0, 122.3, 122.3, 126.0, 127.2, 127.4, 128.0, 128.7, 128.8, 129.5, 131.9, 136.7, 137.5, 137.6, 139.4, 146.8, 149.7, 155.1, 160.0. (Z) -4'-(2-hydroxyethanesulfonyl) -3- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D1) 1 H-NMR (CDCl 3 ) δ: 8.63 (1H, d, J = 4.5 Hz), 8.01 (2H, d, J = 7.9 Hz), 7.82 (3H, d, J = 8.5 Hz), 7.69 (3H, dt, J = 24.6, 8.2 Hz), 7.53 (2H, dd, J = 16.4, 7.4 Hz), 7.42 (1H, d, J = 7.9 Hz), 7.26 (1H, d, J = 15.9 Hz), 7.19 (1H, dd, J = 7.4, 4.5 Hz), 4.56 ( 2H, t, J = 6.2 Hz), 3.54 (2H, t, J = 6.2 Hz) .; 13 C-NMR (CDCl 3 ) δ: 54.9, 57.0, 122.3, 122.3, 126.0, 127.2, 127.4, 128.0, 128.7 , 128.8, 129.5, 131.9, 136.7, 137.5, 137.6, 139.4, 146.8, 149.7, 155.1, 160.0.

(Z)-2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D2) 1H-NMR (CDCl3) δ: 8.60 (1H, d, J= 4.1 Hz), 8.02 (2H, t, J = 4.4 Hz), 7.78 (2H, dd, J = 8.2, 1.4 Hz), 7.71-7.58 (4H, m), 7.39 (1H, d, J = 7.8 Hz), 7.22-7.13 (3H, m), 4.06 (2H, t, J = 5.5 Hz), 3.43 (2H, t, J = 5.5 Hz), 3.28 (1H, s).; 13C-NMR (CDCl3) δ: 56.2, 58.3, 116.8 (d, J = 23.0 Hz), 122.3 (d, J = 14.4 Hz), 127.2 (d, J = 14.4 Hz), 128.1, 128.4, 128.9 (d, J = 8.6 Hz), 129.9 (d, J = 3.8 Hz), 133.5 (d, J = 3.8 Hz),136.7, 138.1, 141.4 (d, J = 1.9 Hz), 149.6, 155.0, 158.2, 160.4. (Z) -2-fluoro-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D2) 1 H-NMR (CDCl 3 ) δ: 8.60 (1H, d, J = 4.1 Hz), 8.02 (2H, t, J = 4.4 Hz), 7.78 (2H, dd, J = 8.2, 1.4 Hz), 7.71-7.58 (4H, m), 7.39 (1H) , d, J = 7.8 Hz), 7.22-7.13 (3H, m), 4.06 (2H, t, J = 5.5 Hz), 3.43 (2H, t, J = 5.5 Hz), 3.28 (1H, s) .; 13 C-NMR (CDCl 3 ) δ: 56.2, 58.3, 116.8 (d, J = 23.0 Hz), 122.3 (d, J = 14.4 Hz), 127.2 (d, J = 14.4 Hz), 128.1, 128.4, 128.9 ( d, J = 8.6 Hz), 129.9 (d, J = 3.8 Hz), 133.5 (d, J = 3.8 Hz), 136.7, 138.1, 141.4 (d, J = 1.9 Hz), 149.6, 155.0, 158.2, 160.4.

(Z)-4'-(2-hydroxyethanesulfonyl)-3-(6-methylpyridin-2-yl-2-vinyl)-1,1'-biphenyl (D3) 1H-NMR (CDCl3) δ: 7.98 (2H, dd, J = 6.4, 1.8 Hz), 7.76 (3H, t, J = 4.1 Hz), 7.63-7.55 (3H, m), 7.47 (2H, tt, J = 8.9, 3.6 Hz), 7.25 (2H, dd, J = 16.5, 9.2 Hz), 7.03 (1H, d, J = 7.8 Hz), 4.03 (2H, t, J= 5.7 Hz), 3.44 (1H, br s), 3.42-3.40 (2H, m), 2.58 (3H, s).; 13C-NMR (CDCl3) δ: 24.4, 56.0, 58.2, 118.8, 122.0, 125.9, 127.0, 127.1, 127.9, 128.4, 129.0, 129.3, 131.6, 136.8, 137.4, 137.5, 139.2, 146.4, 154.5, 158.2. (Z) -4'-(2-hydroxyethanesulfonyl) -3- (6-methylpyridin-2-yl-2-vinyl) -1,1'-biphenyl (D3) 1 H-NMR (CDCl 3 ) δ: 7.98 ( 2H, dd, J = 6.4, 1.8 Hz), 7.76 (3H, t, J = 4.1 Hz), 7.63-7.55 (3H, m), 7.47 (2H, tt, J = 8.9, 3.6 Hz), 7.25 (2H) , dd, J = 16.5, 9.2 Hz), 7.03 (1H, d, J = 7.8 Hz), 4.03 (2H, t, J = 5.7 Hz), 3.44 (1H, br s), 3.42-3.40 (2H, m) ), 2.58 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 24.4, 56.0, 58.2, 118.8, 122.0, 125.9, 127.0, 127.1, 127.9, 128.4, 129.0, 129.3, 131.6, 136.8, 137.4, 137.5, 139.2, 146.4, 154.5, 158.2.

(Z)-2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(6-methylpyridin-2-yl-2-vinyl)-1,1'-biphenyl (D4) 1H-NMR (CDCl3) δ: 8.01-7.98 (2H, m), 7.75 (2H, dd, J = 8.5, 1.1 Hz), 7.63 (1H, dd, J = 7.3, 2.3 Hz), 7.57 (3H, dq, J = 13.2, 3.5 Hz), 7.24 (1H, d, J = 7.8 Hz), 7.16 (2H, dt, J = 15.9, 6.6 Hz), 7.04 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.7 Hz), 3.47 (1H, s), 3.42 (2H, t, J = 5.7 Hz), 2.57 (3H, s).; 13C-NMR (CDCl3) δ: 24.3, 56.0, 58.2, 116.7 (d, J = 23.0 Hz), 118.9, 122.0, 127.0 (d, J = 13.4 Hz), 128.0, 128.7 (d, J = 2.9 Hz), 128.7, 129.0 (d, J = 2.9 Hz), 129.8 (d, J= 2.9 Hz), 130.5, 133.5 (d, J = 3.8 Hz), 136.8, 138.0, 141.2, 154.4, 158.0, 158.2, 160.5.; 19F-NMR (CDCl3) δ: -17.7. (Z) -2-fluoro-4'-(2-hydroxyethanesulfonyl) -5- (6-methylpyridin-2-yl-2-vinyl) -1,1'-biphenyl (D4) 1 H-NMR (CDCl 3 ) δ: 8.01-7.98 (2H, m), 7.75 (2H, dd, J = 8.5, 1.1 Hz), 7.63 (1H, dd, J = 7.3, 2.3 Hz), 7.57 (3H, dq, J = 13.2, 3.5) Hz), 7.24 (1H, d, J = 7.8 Hz), 7.16 (2H, dt, J = 15.9, 6.6 Hz), 7.04 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.7) Hz), 3.47 (1H, s), 3.42 (2H, t, J = 5.7 Hz), 2.57 (3H, s).; 13 C-NMR (CDCl 3 ) δ: 24.3, 56.0, 58.2, 116.7 (d, J = 23.0 Hz), 118.9, 122.0, 127.0 (d, J = 13.4 Hz), 128.0, 128.7 (d, J = 2.9 Hz), 128.7, 129.0 (d, J = 2.9 Hz), 129.8 (d, J = 2.9 Hz), 130.5, 133.5 (d, J = 3.8 Hz), 136.8, 138.0, 141.2, 154.4, 158.0, 158.2, 160.5 .; 19 F-NMR (CDCl 3 ) δ: -17.7.

(Z)-3-tert-butyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D5) 1H-NMR (CDCl3) δ: 8.62 (1H, d, J= 4.1 Hz), 8.02 (2H, t, J = 4.4 Hz), 7.82 (2H, t, J = 4.1 Hz), 7.70 (3H, ddd, J = 13.1, 6.4, 3.9 Hz), 7.64 (1H, s), 7.54 (1H, t, J= 1.6 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.26 (2H, t, J = 8.0 Hz), 7.18 (1H, ddd, J = 7.6, 4.8, 0.9 Hz), 4.05 (2H, t, J = 5.3 Hz), 3.41 (2H, t, J = 5.3 Hz), 2.89 (1H, t, J = 1.8 Hz), 1.41 (9H, s).; 13C-NMR (CDCl3) δ: 31.3, 34.9, 56.4, 58.4, 122.1, 122.3, 123.2, 124.6, 124.9, 128.3, 128.5, 128.6, 132.5, 136.6, 137.2, 137.4, 139.3, 147.5, 149.7, 152.6, 155.4. (Z) -3-tert-butyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D5) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, d, J = 4.1 Hz), 8.02 (2H, t, J = 4.4 Hz), 7.82 (2H, t, J = 4.1 Hz), 7.70 (3H, ddd, J = 13.1, 6.4, 3.9 Hz), 7.64 (1H, s), 7.54 (1H, t, J = 1.6 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.26 (2H, t, J = 8.0 Hz), 7.18 (1H) , ddd, J = 7.6, 4.8, 0.9 Hz), 4.05 (2H, t, J = 5.3 Hz), 3.41 (2H, t, J = 5.3 Hz), 2.89 (1H, t, J = 1.8 Hz), 1.41 (9H, s) .; 13 C-NMR (CDCl 3 ) δ: 31.3, 34.9, 56.4, 58.4, 122.1, 122.3, 123.2, 124.6, 124.9, 128.3, 128.5, 128.6, 132.5, 136.6, 137.2, 137.4, 139.3 , 147.5, 149.7, 152.6, 155.4.

(Z)-4'-(2-hydroxyethanesulfonyl)-3-methyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D6) 1H-NMR (CDCl3) δ: 8.59 (1H, d, J= 4.1 Hz), 7.92 (2H, t, J = 4.1 Hz), 7.60 (2H, t, J = 4.1 Hz), 7.50 (1H, td, J = 7.8, 1.8 Hz), 7.29 (2H, t, J = 8.0 Hz), 7.22 (1H, d, J = 7.8 Hz), 7.14 (2H, t, J = 5.7 Hz), 6.83 (1H, d, J= 12.4 Hz), 6.74 (1H, d, J = 12.8 Hz), 4.02 (2H, t, J = 5.5 Hz), 3.38 (2H, dd, J = 6.6, 4.4 Hz), 3.31 (1H, s), 2.36 (3H, s).; 13C-NMR (CDCl3) δ: 21.3, 56.2, 58.3, 122.0, 124.0, 125.2, 127.3, 127.8, 128.4, 130.0, 130.8, 132.7, 135.8, 137.2, 137.3, 138.7, 138.8, 146.7, 149.5, 156.1. (Z) -4'-(2-hydroxyethanesulfonyl) -3-methyl-5-(pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D6) 1 H-NMR (CDCl 3 ) δ: 8.59 (1H, d, J = 4.1 Hz), 7.92 (2H, t, J = 4.1 Hz), 7.60 (2H, t, J = 4.1 Hz), 7.50 (1H, td, J = 7.8, 1.8 Hz), 7.29 (2H, t, J = 8.0 Hz), 7.22 (1H, d, J = 7.8 Hz), 7.14 (2H, t, J = 5.7 Hz), 6.83 (1H, d, J = 12.4 Hz), 6.74 ( 1H, d, J = 12.8 Hz), 4.02 (2H, t, J = 5.5 Hz), 3.38 (2H, dd, J = 6.6, 4.4 Hz), 3.31 (1H, s), 2.36 (3H, s). 13 C-NMR (CDCl 3 ) δ: 21.3, 56.2, 58.3, 122.0, 124.0, 125.2, 127.3, 127.8, 128.4, 130.0, 130.8, 132.7, 135.8, 137.2, 137.3, 138.7, 138.8, 146.7, 149.5, 156.1 ..

(Z)-4'-(2-hydroxyethanesulfonyl)-3-(pyridin-2-yl-2-vinyl)-5-trifluoromethyl-1,1'-biphenyl (D7) 1H-NMR (CDCl3) δ: 8.63 (1H, dd, J= 4.8, 1.1 Hz), 8.05 (2H, dt, J = 8.7, 1.8 Hz), 7.91 (2H, d, J = 28.9 Hz), 7.82-7.80 (2H, m), 7.72 (3H, dd, J = 8.7, 6.9 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.30 (1H, t, J = 9.8 Hz), 7.22 (1H, ddd, J= 7.4, 4.7, 1.0 Hz), 4.07 (2H, t, J = 5.0 Hz), 3.45-3.42 (2H, m), 3.26 (1H, s).; 13C-NMR (CDCl3) δ: 56.2, 58.4, 122.7 (d, J = 19.2 Hz), 123.5 (q, J = 1.9 Hz), 123.6 (q, J = 272.8 Hz), 128.2, 128.7, 129.1, 130.5, 132.0 (d, J= 9.6 Hz), 132.0 (q, J = 32.6 Hz), 136.8, 138.5, 138.6, 140.3, 145.2, 149.8, 154.5.; 19F-NMR (CDCl3) δ: 37.4. (Z) -4'-(2-hydroxyethanesulfonyl) -3- (pyridin-2-yl-2-vinyl) -5-trifluoromethyl-1,1'-biphenyl (D7) 1 H-NMR (CDCl 3 ) δ: 8.63 (1H, dd, J = 4.8, 1.1 Hz), 8.05 (2H, dt, J = 8.7, 1.8 Hz), 7.91 (2H, d, J = 28.9 Hz), 7.82-7.80 (2H, m), 7.72 (3H, dd, J = 8.7, 6.9 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.30 (1H, t, J = 9.8 Hz), 7.22 (1H, ddd, J = 7.4, 4.7, 1.0) Hz), 4.07 (2H, t, J = 5.0 Hz), 3.45-3.42 (2H, m), 3.26 (1H, s).; 13 C-NMR (CDCl 3 ) δ: 56.2, 58.4, 122.7 (d, s). J = 19.2 Hz), 123.5 (q, J = 1.9 Hz), 123.6 (q, J = 272.8 Hz), 128.2, 128.7, 129.1, 130.5, 132.0 (d, J = 9.6 Hz), 132.0 (q, J = 32.6 Hz), 136.8, 138.5, 138.6, 140.3, 145.2, 149.8, 154.5 .; 19 F-NMR (CDCl 3 ) δ: 37.4.

(Z)-4'-(2-hydroxyethanesulfonyl)-4-methyl-3-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D8) 1H-NMR (CDCl3) δ: 8.56 (1H, dq, J= 5.0, 0.9 Hz), 7.89 (2H, dt, J = 8.5, 2.1 Hz), 7.54 (2H, dt, J = 8.7, 2.1 Hz), 7.41 (3H, tt, J = 12.1, 4.0 Hz), 7.33 (1H, d, J = 8.2 Hz), 7.08 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.99 (1H, d, J = 7.8 Hz), 6.93 (1H, d, J = 12.4 Hz), 6.84 (1H, d, J = 12.4 Hz), 4.01 (2H, t, J = 5.3 Hz), 3.38-3.35 (2H, m), 3.28 (1H, s), 2.35 (3H, s).; 13C-NMR (CDCl3) δ: 19.6, 56.2, 58.3, 121.9, 123.5, 126.4, 127.5, 127.9, 128.4, 131.0, 131.7, 132.0, 135.7, 136.2, 137.0, 137.1, 146.4, 149.4, 155.9. (Z) -4'-(2-hydroxyethanesulfonyl) -4-methyl-3- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D8) 1 H-NMR (CDCl 3 ) δ: 8.56 (1H, dq, J = 5.0, 0.9 Hz), 7.89 (2H, dt, J = 8.5, 2.1 Hz), 7.54 (2H, dt, J = 8.7, 2.1 Hz), 7.41 (3H, tt, J = 12.1, 4.0 Hz), 7.33 (1H, d, J = 8.2 Hz), 7.08 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.99 (1H, d, J = 7.8 Hz), 6.93 (1H, d, J = 12.4 Hz), 6.84 (1H, d, J = 12.4 Hz), 4.01 (2H, t, J = 5.3 Hz), 3.38-3.35 (2H, m), 3.28 (1H, s), 2.35 ( 3H, s) .; 13 C-NMR (CDCl 3 ) δ: 19.6, 56.2, 58.3, 121.9, 123.5, 126.4, 127.5, 127.9, 128.4, 131.0, 131.7, 132.0, 135.7, 136.2, 137.0, 137.1, 146.4, 149.4, 155.9.

(Z)-4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl-2-vinyl)-1,1'-biphenyl (D9) 1H-NMR (CDCl3) δ: 8.47 (1H, dd, J = 4.6, 1.4 Hz), 8.00 (2H, dt, J = 8.4, 1.9 Hz), 7.86-7.78 (4H, m), 7.67 (1H, dt, J = 7.0, 1.6 Hz), 7.50 (3H, dq, J = 12.7, 4.0 Hz), 7.41 (1H, d, J = 15.6 Hz), 7.10 (1H, dd, J = 7.6, 4.8 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.42-3.39 (2H, m), 3.18 (1H, s), 2.46 (3H, s).; 13C-NMR (CDCl3) δ: 18.8, 56.3, 58.3, 122.3, 124.9, 126.2, 127.1, 127.2, 128.0, 128.5, 129.4, 131.0, 132.9, 137.6, 137.9, 138.3, 139.4, 146.7, 147.1, 153.0. (Z) -4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl-2-vinyl) -1,1'-biphenyl (D9) 1 H-NMR (CDCl 3 ) δ: 8.47 ( 1H, dd, J = 4.6, 1.4 Hz), 8.00 (2H, dt, J = 8.4, 1.9 Hz), 7.86-7.78 (4H, m), 7.67 (1H, dt, J = 7.0, 1.6 Hz), 7.50 (3H, dq, J = 12.7, 4.0 Hz), 7.41 (1H, d, J = 15.6 Hz), 7.10 (1H, dd, J = 7.6, 4.8 Hz), 4.04 (2H, t, J = 5.5 Hz) , 3.42-3.39 (2H, m), 3.18 (1H, s), 2.46 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 18.8, 56.3, 58.3, 122.3, 124.9, 126.2, 127.1, 127.2 , 128.0, 128.5, 129.4, 131.0, 132.9, 137.6, 137.9, 138.3, 139.4, 146.7, 147.1, 153.0.

(Z)-4'-(2-hydroxyethanesulfonyl)-3-(6-methylpyridin-2-yl-2-vinyl)-4-methyl-1,1'-biphenyl (D10) 1H-NMR (CDCl3) δ: 8.01-7.98 (2H, m), 7.89 (1H, d, J = 1.8 Hz), 7.87-7.81 (3H, m), 7.58 (1H, t, J = 7.8 Hz), 7.45 (1H, dd, J = 7.8, 1.8 Hz), 7.30 (2H, dd, J = 11.2, 8.0 Hz), 7.16 (1H, d, J = 16.0 Hz), 7.05 (1H, d, J = 7.8 Hz), 4.05 (2H, t, J = 5.3 Hz), 3.42-3.39 (2H, m), 2.85 (1H, s), 2.60 (3H, s), 2.53 (3H, s).; 13C-NMR (CDCl3) δ: 19.8, 24.7, 56.4, 58.4, 118.8, 122.0, 124.7, 126.8, 127.9, 128.5, 129.5, 130.7, 131.3, 136.7, 136.7, 136.9, 137.2, 137.2, 146.9, 155.0, 158.4. (Z) -4'-(2-hydroxyethanesulfonyl) -3- (6-methylpyridin-2-yl-2-vinyl) -4-methyl-1,1'-biphenyl (D10) 1 H-NMR (CDCl 3 ) δ: 8.01-7.98 (2H, m), 7.89 (1H, d, J = 1.8 Hz), 7.87-7.81 (3H, m), 7.58 (1H, t, J = 7.8 Hz), 7.45 (1H, dd, J = 7.8, 1.8 Hz), 7.30 (2H, dd, J = 11.2, 8.0 Hz), 7.16 (1H, d, J = 16.0 Hz), 7.05 (1H, d, J = 7.8 Hz), 4.05 (2H, t, J = 5.3 Hz), 3.42-3.39 (2H, m), 2.85 (1H, s), 2.60 (3H, s), 2.53 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 19.8 , 24.7, 56.4, 58.4, 118.8, 122.0, 124.7, 126.8, 127.9, 128.5, 129.5, 130.7, 131.3, 136.7, 136.7, 136.9, 137.2, 137.2, 146.9, 155.0, 158.4.

(Z)-4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl-2-vinyl)-4-methyl-1,1'-biphenyl (D11) 1H-NMR (CDCl3) δ: 8.45 (1H, t, J = 2.3 Hz), 7.82 (2H, dt, J = 8.7, 1.8 Hz), 7.43 (1H, d, J = 6.9 Hz), 7.29 (5H, ddt, J = 18.1, 9.8, 3.9 Hz), 7.13 (1H, dd, J = 7.6, 4.8 Hz), 7.06 (1H, d, J = 1.8 Hz), 6.96 (1H, d, J = 12.4 Hz), 6.86 (1H, d, J = 11.9 Hz), 4.00 (2H, d, J = 5.0 Hz), 3.34 (2H, td, J = 4.1, 2.0 Hz), 2.90 (1H, s), 2.41 (3H, s), 2.05 (3H, s).; 13C-NMR (CDCl3) δ: 18.6, 19.6, 56.4, 58.3, 122.1, 126.1, 127.4, 128.1, 129.6, 130.9, 131.4, 131.5, 135.6, 136.6, 136.8, 137.1, 138.0, 146.6, 147.0, 155.9. (Z) -4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl-2-vinyl) -4-methyl-1,1'-biphenyl (D11) 1 H-NMR (CDCl 3 ) δ: 8.45 (1H, t, J = 2.3 Hz), 7.82 (2H, dt, J = 8.7, 1.8 Hz), 7.43 (1H, d, J = 6.9 Hz), 7.29 (5H, ddt, J = 18.1, 9.8, 3.9 Hz), 7.13 (1H, dd, J = 7.6, 4.8 Hz), 7.06 (1H, d, J = 1.8 Hz), 6.96 (1H, d, J = 12.4 Hz), 6.86 (1H, d, J = 11.9 Hz), 4.00 (2H, d, J = 5.0 Hz), 3.34 (2H, td, J = 4.1, 2.0 Hz), 2.90 (1H, s), 2.41 (3H, s), 2.05 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 18.6, 19.6, 56.4, 58.3, 122.1, 126.1, 127.4, 128.1, 129.6, 130.9, 131.4, 131.5, 135.6, 136.6, 136.8, 137.1, 138.0, 146.6, 147.0, 155.9.

(Z)-4'-(2-hydroxyethanesulfonyl)-2-methyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D12) 1H-NMR (CDCl3) δ: 8.55 (1H, dq, J= 4.9, 0.9 Hz), 7.93 (2H, dt, J = 8.6, 1.9 Hz), 7.52 (1H, td, J = 7.7, 1.7 Hz), 7.42 (2H, dt, J = 8.6, 1.9 Hz), 7.26-7.11 (5H, m), 6.79 (1H, d, J = 12.4 Hz), 6.67 (1H, d, J = 12.4 Hz), 4.04 (2H, t, J= 5.6 Hz), 3.63 (1H, s), 3.43-3.40 (2H, m), 2.23 (3H, s).; 13C-NMR (CDCl3) δ: 14.0, 23.7, 35.4, 56.2, 58.3, 121.8, 123.6, 126.5, 127.5, 128.3, 128.4, 130.3, 131.7, 132.1, 135.7, 136.2, 136.6, 137.1, 141.7, 146.4, 149.5, 155.8. (Z) -4'-(2-hydroxyethanesulfonyl) -2-methyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D12) 1 H-NMR (CDCl 3 ) δ: 8.55 (1H, dq, J = 4.9, 0.9 Hz), 7.93 (2H, dt, J = 8.6, 1.9 Hz), 7.52 (1H, td, J = 7.7, 1.7 Hz), 7.42 (2H, dt, J = 8.6, 1.9 Hz), 7.26-7.11 (5H, m), 6.79 (1H, d, J = 12.4 Hz), 6.67 (1H, d, J = 12.4 Hz), 4.04 (2H, t, J = 5.6 Hz) , 3.63 (1H, s), 3.43-3.40 (2H, m), 2.23 (3H, s) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 23.7, 35.4, 56.2, 58.3, 121.8, 123.6, 126.5 , 127.5, 128.3, 128.4, 130.3, 131.7, 132.1, 135.7, 136.2, 136.6, 137.1, 141.7, 146.4, 149.5, 155.8.

(Z)-4'-(2-hydroxyethanesulfonyl)-4-propyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D14) 1H-NMR (CDCl3) δ: 8.57 (1H, dq, J= 5.0, 1.0 Hz), 7.88 (2H, dt, J = 8.6, 2.0 Hz), 7.53-7.51 (2H, m), 7.46 (1H, dd, J = 8.0, 1.9 Hz), 7.40-7.34 (3H, m), 7.08 (1H, ddd, J = 7.5, 4.9, 1.0 Hz), 6.99 (2H, dd, J = 16.1, 10.2 Hz), 6.84 (1H, d, J= 12.4 Hz), 4.00 (2H, t, J = 5.5 Hz), 3.38-3.35 (3H, m), 2.68 (2H, dd, J= 8.6, 6.9 Hz), 1.70-1.64 (2H, m), 1.00 (3H, t, J = 7.2 Hz).; 13C-NMR (CDCl3) δ: 20.1, 56.1, 58.2, 121.9, 123.9, 127.7, 128.7, 130.0, 130.0, 130.1, 130.6, 132.5, 134.2, 134.6, 135.8, 137.3, 139.5, 147.5, 149.3, 156.1. (Z) -4'-(2-hydroxyethanesulfonyl) -4-propyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D14) 1 H-NMR (CDCl 3 ) δ: 8.57 (1H, dq, J = 5.0, 1.0 Hz), 7.88 (2H, dt, J = 8.6, 2.0 Hz), 7.53-7.51 (2H, m), 7.46 (1H, dd, J = 8.0, 1.9 Hz) , 7.40-7.34 (3H, m), 7.08 (1H, ddd, J = 7.5, 4.9, 1.0 Hz), 6.99 (2H, dd, J = 16.1, 10.2 Hz), 6.84 (1H, d, J = 12.4 Hz) ), 4.00 (2H, t, J = 5.5 Hz), 3.38-3.35 (3H, m), 2.68 (2H, dd, J = 8.6, 6.9 Hz), 1.70-1.64 (2H, m), 1.00 (3H, m) t, J = 7.2 Hz) .; 13 C-NMR (CDCl 3 ) δ: 20.1, 56.1, 58.2, 121.9, 123.9, 127.7, 128.7, 130.0, 130.0, 130.1, 130.6, 132.5, 134.2, 134.6, 135.8, 137.3 , 139.5, 147.5, 149.3, 156.1.

(Z)-4-ethoxy-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D15) 1H-NMR (CDCl3) δ: 8.62 (1H, dq, J= 4.8, 0.9 Hz), 7.97 (3H, dt, J = 13.7, 5.8 Hz), 7.89 (1H, d, J = 2.4 Hz), 7.80 (2H, dt, J = 8.7, 2.0 Hz), 7.68 (1H, td, J = 7.7, 1.8 Hz), 7.52 (1H, dd, J = 8.6, 2.4 Hz), 7.47 (1H, t, J = 4.0 Hz), 7.35 (1H, d, J = 16.4 Hz), 7.16 (1H, ddd, J = 7.5, 4.8, 1.1 Hz), 7.02 (1H, d, J = 8.6 Hz), 4.20 (2H, q, J = 7.0 Hz), 4.05 (2H, s), 3.42-3.39 (2H, m), 1.55 (3H, t, J = 7.0 Hz).; 13C-NMR (CDCl3) δ: 14.8, 56.5, 58.4, 64.2, 112.4, 121.9, 122.1, 126.5, 126.6, 127.5, 128.2, 128.6, 129.7, 131.1, 136.5, 136.7, 146.6, 149.7, 156.0, 157.5, 158.7. (Z) -4-ethoxy-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D15) 1 H-NMR (CDCl 3 ) δ: 8.62 (1H, dq, J = 4.8, 0.9 Hz), 7.97 (3H, dt, J = 13.7, 5.8 Hz), 7.89 (1H, d, J = 2.4 Hz), 7.80 (2H, dt, J = 8.7, 2.0 Hz), 7.68 (1H, td, J = 7.7, 1.8 Hz), 7.52 (1H, dd, J = 8.6, 2.4 Hz), 7.47 (1H, t, J = 4.0 Hz), 7.35 (1H, d, J = 16.4 Hz), 7.16 (1H, ddd, J = 7.5, 4.8, 1.1 Hz), 7.02 (1H, d, J = 8.6 Hz), 4.20 (2H, q, J = 7.0 Hz), 4.05 (2H, s), 3.42-3.39 (2H, m), 1.55 (3H, t, J = 7.0 Hz).; 13 C-NMR (CDCl 3 ) δ: 14.8, 56.5, 58.4, 64.2, 112.4, 121.9, 122.1, 126.5 , 126.6, 127.5, 128.2, 128.6, 129.7, 131.1, 136.5, 136.7, 146.6, 149.7, 156.0, 157.5, 158.7.

(E)-4'-(2-hydroxyethanesulfonyl)-4-pentyl-3-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D16) 1H-NMR (CDCl3) δ: 8.57 (1H, d, J= 4.1 Hz), 7.88 (2H, d, J = 8.7 Hz), 7.52 (2H, d, J = 8.7 Hz), 7.46 (1H, dd, J = 8.0, 2.1 Hz), 7.36 (3H, td, J = 9.8, 4.0 Hz), 7.07 (1H, t, J = 6.2 Hz), 6.99 (2H, dd, J = 14.7, 10.1 Hz), 6.84 (1H, d, J = 12.4 Hz), 4.00 (2H, t, J = 5.7 Hz), 3.36 (3H, t, J= 5.5 Hz), 2.69 (2H, t, J = 7.8 Hz), 1.63 (2H, t, J = 7.6 Hz), 1.35 (4H, dd, J = 7.3, 3.7 Hz), 0.89 (3H, t, J = 7.1 Hz).; 13C-NMR (CDCl3) δ: 13.9, 22.4, 30.1, 31.6, 33.3, 56.2, 58.3, 121.8, 123.6, 126.5, 127.5, 128.3, 128.4, 130.2, 131.7, 132.1, 135.6, 136.2, 136.5, 137.1, 142.0, 146.4, 149.4, 155.9. (E) -4'-(2-hydroxyethanesulfonyl) -4-pentyl-3- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D16) 1 H-NMR (CDCl 3 ) δ: 8.57 (1H, d, J = 4.1 Hz), 7.88 (2H, d, J = 8.7 Hz), 7.52 (2H, d, J = 8.7 Hz), 7.46 (1H, dd, J = 8.0, 2.1 Hz), 7.36 (3H, td, J = 9.8, 4.0 Hz), 7.07 (1H, t, J = 6.2 Hz), 6.99 (2H, dd, J = 14.7, 10.1 Hz), 6.84 (1H, d, J = 12.4 Hz) ), 4.00 (2H, t, J = 5.7 Hz), 3.36 (3H, t, J = 5.5 Hz), 2.69 (2H, t, J = 7.8 Hz), 1.63 (2H, t, J = 7.6 Hz), 1.35 (4H, dd, J = 7.3, 3.7 Hz), 0.89 (3H, t, J = 7.1 Hz) .; 13 C-NMR (CDCl 3 ) δ: 13.9, 22.4, 30.1, 31.6, 33.3, 56.2, 58.3 , 121.8, 123.6, 126.5, 127.5, 128.3, 128.4, 130.2, 131.7, 132.1, 135.6, 136.2, 136.5, 137.1, 142.0, 146.4, 149.4, 155.9.

(Z)-4'-(2-hydroxyethanesulfonyl)-4-iso-propyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D17) 1H-NMR (CDCl3) δ: 8.56 (1H, dq, J= 5.0, 0.9 Hz), 7.89 (2H, dd, J = 6.9, 1.8 Hz), 7.55-7.51 (3H, m), 7.45 (1H, d, J = 8.2 Hz), 7.36 (2H, td, J = 7.8, 1.8 Hz), 7.08-7.05 (2H, m), 6.93 (1H, d, J = 8.2 Hz), 6.85 (1H, d, J = 12.4 Hz), 4.00 (2H, t, J = 5.5 Hz), 3.37 (2H, dd, J = 6.9, 4.1 Hz), 3.25 (1H, t, J = 6.9 Hz), 1.26 (6H, d, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 23.2, 30.0, 56.1, 58.3, 121.8, 123.6, 126.2, 126.9, 127.5, 128.2, 128.4, 131.9, 132.3, 135.6, 136.1, 136.1, 137.2, 146.3, 147.5, 149.4, 155.7. (Z) -4'-(2-hydroxyethanesulfonyl) -4-iso-propyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D17) 1 H-NMR (CDCl 3 ) δ: 8.56 (1H, dq, J = 5.0, 0.9 Hz), 7.89 (2H, dd, J = 6.9, 1.8 Hz), 7.55-7.51 (3H, m), 7.45 (1H, d, J = 8.2 Hz) , 7.36 (2H, td, J = 7.8, 1.8 Hz), 7.08-7.05 (2H, m), 6.93 (1H, d, J = 8.2 Hz), 6.85 (1H, d, J = 12.4 Hz), 4.00 ( 2H, t, J = 5.5 Hz), 3.37 (2H, dd, J = 6.9, 4.1 Hz), 3.25 (1H, t, J = 6.9 Hz), 1.26 (6H, d, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 23.2, 30.0, 56.1, 58.3, 121.8, 123.6, 126.2, 126.9, 127.5, 128.2, 128.4, 131.9, 132.3, 135.6, 136.1, 136.1, 137.2, 146.3, 147.5, 149.4, 155.7 ..

(Z)-4-iso-butyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D18) 1H-NMR (CDCl3) δ: 8.57 (1H, td, J= 2.5, 1.2 Hz), 7.88 (2H, dd, J = 8.7, 1.8 Hz), 7.51 (2H, dt, J = 8.5, 2.1 Hz), 7.45 (1H, dd, J = 8.0, 2.1 Hz), 7.40-7.35 (2H, m), 7.31 (1H, d, J = 7.8 Hz), 7.07 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.99 (2H, dd, J = 13.3, 10.1 Hz), 6.82 (1H, d, J = 12.4 Hz), 4.00 (2H, dd, J = 6.9, 4.1 Hz), 3.50 (1H, br s), 3.38-3.35 (2H, m), 2.59 (2H, d, J= 7.3 Hz), 1.98 (1H, t, J = 6.6 Hz), 0.96 (6H, d, J = 6.4 Hz).; 13C-NMR (CDCl3) δ: 22.5, 29.3, 42.5, 56.1, 58.3, 121.8, 123.5, 126.3, 127.5, 127.6, 128.3, 131.2, 131.6, 132.3,135.6, 136.2, 136.8, 137.2, 140.9, 146.3, 149.4, 155.9. (Z) -4-iso-butyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D18) 1 H-NMR (CDCl 3 ) δ: 8.57 (1H, td, J = 2.5, 1.2 Hz), 7.88 (2H, dd, J = 8.7, 1.8 Hz), 7.51 (2H, dt, J = 8.5, 2.1 Hz), 7.45 (1H, dd, J = 8.0, 2.1 Hz), 7.40-7.35 (2H, m), 7.31 (1H, d, J = 7.8 Hz), 7.07 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.99 (2H, dd) , J = 13.3, 10.1 Hz), 6.82 (1H, d, J = 12.4 Hz), 4.00 (2H, dd, J = 6.9, 4.1 Hz), 3.50 (1H, br s), 3.38-3.35 (2H, m) ), 2.59 (2H, d, J = 7.3 Hz), 1.98 (1H, t, J = 6.6 Hz), 0.96 (6H, d, J = 6.4 Hz) .; 13 C-NMR (CDCl 3 ) δ: 22.5 , 29.3, 42.5, 56.1, 58.3, 121.8, 123.5, 126.3, 127.5, 127.6, 128.3, 131.2, 131.6, 132.3, 135.6, 136.2, 136.8, 137.2, 140.9, 146.3, 149.4, 155.9.

(Z)-4'-(2-hydroxyethanesulfonyl)-3-(3-methylpyridin-2-yl-2-vinyl)-4-propyl-1,1'-biphenyl (D19) 1H-NMR (CDCl3) δ: 8.49 (1H, dd, J = 4.8, 1.7 Hz), 8.10 (1H, d, J = 15.4 Hz), 8.00 (2H, dt, J = 8.6, 2.0 Hz), 7.86 (4H, ddd, J = 14.8, 9.5, 7.5 Hz), 7.49 (2H, tdd, J = 5.2, 2.6, 1.2 Hz), 7.32 (2H, t, J= 7.6 Hz), 7.11 (1H, dd, J = 7.6, 4.8 Hz), 4.55 (2H, td, J = 6.3, 0.8 Hz), 3.53 (2H, t, J = 6.2 Hz), 2.85 (2H, t, J = 7.7 Hz), 2.46 (3H, s), 1.78 (1H, br s), 1.71 (2H, dd, J = 15.3, 7.4 Hz), 1.01 (3H, t, J= 7.3 Hz).; 13C-NMR (CDCl3) δ: 14.0, 19.0, 24.1, 35.1, 54.9, 57.0, 122.3, 125.1, 126.6, 126.8, 127.9, 128.6, 130.5, 130.9, 131.2, 136.7, 136.9, 137.3, 138.3, 142.2, 147.0, 147.1, 153.3, 160.0. (Z) -4'-(2-hydroxyethanesulfonyl) -3- (3-methylpyridin-2-yl-2-vinyl) -4-propyl-1,1'-biphenyl (D19) 1 H-NMR (CDCl 3 ) δ: 8.49 (1H, dd, J = 4.8, 1.7 Hz), 8.10 (1H, d, J = 15.4 Hz), 8.00 (2H, dt, J = 8.6, 2.0 Hz), 7.86 (4H, ddd, J = 14.8, 9.5, 7.5 Hz), 7.49 (2H, tdd, J = 5.2, 2.6, 1.2 Hz), 7.32 (2H, t, J = 7.6 Hz), 7.11 (1H, dd, J = 7.6, 4.8 Hz), 4.55 (2H, td, J = 6.3, 0.8 Hz), 3.53 (2H, t, J = 6.2 Hz), 2.85 (2H, t, J = 7.7 Hz), 2.46 (3H, s), 1.78 (1H, br) s), 1.71 (2H, dd, J = 15.3, 7.4 Hz), 1.01 (3H, t, J = 7.3 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 19.0, 24.1, 35.1, 54.9, 57.0, 122.3, 125.1, 126.6, 126.8, 127.9, 128.6, 130.5, 130.9, 131.2, 136.7, 136.9, 137.3, 138.3, 142.2, 147.0, 147.1, 153.3, 160.0.

(Z)-4'-(2-hydroxyethanesulfonyl)-3-(3-penthylpyridin-2-yl-2-vinyl)-4-propyl-1,1'-biphenyl (D21) 1H-NMR (CDCl3) δ: 8.50 (1H, dd, J = 4.7, 1.6 Hz), 8.10 (1H, d, J = 15.4 Hz), 8.00 (2H, dt, J = 8.6, 2.0 Hz), 7.86 (4H, ddd, J = 13.4, 10.0, 7.5 Hz), 7.49 (2H, td, J = 7.6, 1.9 Hz), 7.31 (2H, dd, J= 14.6, 11.7 Hz), 7.13 (1H, dd, J = 7.7, 4.7 Hz), 4.55 (2H, td, J= 6.3, 0.8 Hz), 3.54 (2H, t, J = 6.3 Hz), 2.85 (2H, t, J = 7.7 Hz), 2.76 (2H, t, J = 7.7 Hz), 1.68 (5H, dq, J = 27.8, 6.1 Hz), 1.37 (4H, td, J = 7.1, 3.7 Hz), 1.01 (3H, t, J = 7.2 Hz), 0.89 (3H, dt, J = 8.3, 3.1 Hz).; 13C-NMR (CDCl3) δ: 14.0, 14.0, 22.5, 24.1, 30.5, 31.5, 32.4, 35.2, 54.9, 57.0, 122.3, 125.3, 126.7, 126.7, 127.8, 128.6, 130.5, 131.1, 135.6, 136.7, 137.2, 137.5, 142.2, 147.1, 147.2, 152.9, 160.0. (Z) -4'-(2-hydroxyethanesulfonyl) -3- (3-penthylpyridin-2-yl-2-vinyl) -4-propyl-1,1'-biphenyl (D21) 1 H-NMR (CDCl 3 ) δ: 8.50 (1H, dd, J = 4.7, 1.6 Hz), 8.10 (1H, d, J = 15.4 Hz), 8.00 (2H, dt, J = 8.6, 2.0 Hz), 7.86 (4H, ddd, J = 13.4, 10.0, 7.5 Hz), 7.49 (2H, td, J = 7.6, 1.9 Hz), 7.31 (2H, dd, J = 14.6, 11.7 Hz), 7.13 (1H, dd, J = 7.7, 4.7 Hz), 4.55 (2H, td, J = 6.3, 0.8 Hz), 3.54 (2H, t, J = 6.3 Hz), 2.85 (2H, t, J = 7.7 Hz), 2.76 (2H, t, J = 7.7 Hz), 1.68 (5H, dq, J = 27.8, 6.1 Hz), 1.37 (4H, td, J = 7.1, 3.7 Hz), 1.01 (3H, t, J = 7.2 Hz), 0.89 (3H, dt, J = 8.3, 3.1 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 14.0, 22.5, 24.1, 30.5, 31.5, 32.4, 35.2, 54.9, 57.0, 122.3, 125.3, 126.7, 126.7, 127.8, 128.6, 130.5, 131.1 , 135.6, 136.7, 137.2, 137.5, 142.2, 147.1, 147.2, 152.9, 160.0.

(Z)-4-heptyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D22) 1H-NMR (CDCl3) δ: 8.57 (1H, dd, J= 3.0, 2.1 Hz), 7.89-7.87 (2H, m), 7.52 (2H, dt, J = 8.7, 1.8 Hz), 7.46 (1H, dd, J = 8.0, 1.6 Hz), 7.37 (3H, td, J = 9.8, 3.8 Hz), 7.09-7.06 (1H, m), 6.99 (2H, dd, J = 15.1, 10.1 Hz), 6.84 (1H, d, J= 12.4 Hz), 4.00 (2H, d, J = 5.0 Hz), 3.38-3.35 (2H, m), 3.33 (1H, s), 2.70 (2H, t, J = 7.8 Hz), 1.67-1.59 (2H, m), 1.39-1.26 (8H, m), 0.87 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 14.0, 22.6, 29.1, 29.4, 30.5, 31.7, 33.3, 56.2, 58.3, 121.8, 123.6, 126.5, 127.5, 128.3, 128.4, 130.2, 131.7, 132.1, 135.6, 136.2, 136.5, 137.1, 142.0, 146.4, 149.4, 155.9. (Z) -4-heptyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D22) 1 H-NMR (CDCl 3 ) δ: 8.57 (1H, dd, J = 3.0, 2.1 Hz), 7.89-7.87 (2H, m), 7.52 (2H, dt, J = 8.7, 1.8 Hz), 7.46 (1H, dd, J = 8.0, 1.6 Hz) , 7.37 (3H, td, J = 9.8, 3.8 Hz), 7.09-7.06 (1H, m), 6.99 (2H, dd, J = 15.1, 10.1 Hz), 6.84 (1H, d, J = 12.4 Hz), 4.00 (2H, d, J = 5.0 Hz), 3.38-3.35 (2H, m), 3.33 (1H, s), 2.70 (2H, t, J = 7.8 Hz), 1.67-1.59 (2H, m), 1.39 -1.26 (8H, m), 0.87 (3H, t, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 22.6, 29.1, 29.4, 30.5, 31.7, 33.3, 56.2, 58.3, 121.8 , 123.6, 126.5, 127.5, 128.3, 128.4, 130.2, 131.7, 132.1, 135.6, 136.2, 136.5, 137.1, 142.0, 146.4, 149.4, 155.9.

(Z)-4'-(2-hydroxyethanesulfonyl)-4-octyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D23) 1H-NMR (CDCl3) δ: 8.56 (1H, dd, J= 3.0, 2.1 Hz), 7.88 (2H, d, J = 8.7 Hz), 7.51 (2H, d, J = 8.7 Hz), 7.46 (1H, dd, J = 8.2, 1.8 Hz), 7.40-7.33 (3H, m), 7.09-7.06 (1H, m), 6.99 (2H, dd, J = 13.7, 10.1 Hz), 6.83 (1H, d, J = 12.4 Hz), 4.00 (2H, t, J = 5.7 Hz), 3.66 (1H, s), 3.37 (2H, t, J = 5.7 Hz), 2.69 (2H, t, J = 7.8 Hz), 1.66-1.59 (2H, m), 1.32 (10H, tt, J = 17.9, 5.8 Hz), 0.87 (3H, t, J = 6.6 Hz).; 13C-NMR (CDCl3) δ: 14.0, 22.5, 29.1, 29.3, 29.4, 30.4, 31.7, 33.3, 56.1, 58.3, 121.8, 123.6, 126.5, 127.4, 128.2, 128.3, 130.2, 131.6, 132.1, 135.6, 136.1, 136.4, 137.1, 141.9, 146.2, 149.3, 155.8. (Z) -4'-(2-hydroxyethanesulfonyl) -4-octyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D23) 1 H-NMR (CDCl 3 ) δ: 8.56 (1H, dd, J = 3.0, 2.1 Hz), 7.88 (2H, d, J = 8.7 Hz), 7.51 (2H, d, J = 8.7 Hz), 7.46 (1H, dd, J = 8.2, 1.8 Hz) ), 7.40-7.33 (3H, m), 7.09-7.06 (1H, m), 6.99 (2H, dd, J = 13.7, 10.1 Hz), 6.83 (1H, d, J = 12.4 Hz), 4.00 (2H, t, J = 5.7 Hz), 3.66 (1H, s), 3.37 (2H, t, J = 5.7 Hz), 2.69 (2H, t, J = 7.8 Hz), 1.66-1.59 (2H, m), 1.32 ( 10H, tt, J = 17.9, 5.8 Hz), 0.87 (3H, t, J = 6.6 Hz) .; 13 C-NMR (CDCl 3 ) δ: 14.0, 22.5, 29.1, 29.3, 29.4, 30.4, 31.7, 33.3 , 56.1, 58.3, 121.8, 123.6, 126.5, 127.4, 128.2, 128.3, 130.2, 131.6, 132.1, 135.6, 136.1, 136.4, 137.1, 141.9, 146.2, 149.3, 155.8.

(Z)-4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl)-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D24) 1H-NMR (CDCl3) δ: 8.54 (1H, d, J= 4.6 Hz), 7.88 (2H, d, J = 8.7 Hz), 7.51 (3H, d, J = 8.7 Hz), 7.42 (1H, d, J = 8.2 Hz), 7.35 (2H, dd, J = 11.4, 5.0 Hz), 7.06 (2H, dd, J = 12.4, 5.0 Hz), 6.93 (1H, d, J = 7.8 Hz), 6.84 (1H, d, J = 12.4 Hz), 4.00 (3H, t, J = 5.7 Hz), 3.38 (2H, t, J= 5.7 Hz), 2.83 (1H, t, J = 11.2 Hz), 1.80 (5H, dd, J = 25.4, 15.3 Hz), 1.51-1.25 (5H, m).; 13C-NMR (CDCl3) δ: 25.9, 26.7, 33.4, 40.5, 55.9, 58.2, 121.7, 123.6, 126.7, 126.7, 127.3, 128.0, 128.2, 131.6, 132.4, 135.6, 135.9, 136.0, 137.2, 146.0, 146.4, 149.1, 155.6. (Z) -4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl) -5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D24) 1 H-NMR (CDCl 3 ) δ: 8.54 (1H, d, J = 4.6 Hz), 7.88 (2H, d, J = 8.7 Hz), 7.51 (3H, d, J = 8.7 Hz), 7.42 (1H, d, J = 8.2 Hz), 7.35 (2H, dd, J = 11.4, 5.0 Hz), 7.06 (2H, dd, J = 12.4, 5.0 Hz), 6.93 (1H, d, J = 7.8 Hz), 6.84 (1H, d, J = 12.4 Hz) ), 4.00 (3H, t, J = 5.7 Hz), 3.38 (2H, t, J = 5.7 Hz), 2.83 (1H, t, J = 11.2 Hz), 1.80 (5H, dd, J = 25.4, 15.3 Hz) ), 1.51-1.25 (5H, m) .; 13 C-NMR (CDCl 3 ) δ: 25.9, 26.7, 33.4, 40.5, 55.9, 58.2, 121.7, 123.6, 126.7, 126.7, 127.3, 128.0, 128.2, 131.6, 132.4, 135.6, 135.9, 136.0, 137.2, 146.0, 146.4, 149.1, 155.6.

(Z)-4'-(2-hydroxyethanesulfonyl)-4-cyclo-pentyl-5-(pyridin-2-yl-2-vinyl)-1,1'-biphenyl (D25) 1H-NMR (CDCl3) δ: 8.58 (1H, d, J= 4.1 Hz), 7.89 (2H, dt, J = 8.7, 1.8 Hz), 7.55 (2H, dd, J = 8.7, 1.8 Hz), 7.51 (1H, dd, J = 8.2, 2.3 Hz), 7.46 (1H, d, J = 7.8 Hz), 7.37-7.33 (2H, m), 7.07 (2H, dt, J = 12.4, 3.0 Hz), 6.92 (1H, d, J= 8.2 Hz), 6.85 (1H, d, J = 12.4 Hz), 4.01 (2H, q, J = 5.5 Hz), 3.36 (2H, td, J = 4.1, 2.0 Hz), 3.29 (1H, t, J = 8.5 Hz), 3.04 (1H, s), 2.02 (2H, tt, J = 7.6, 4.0 Hz), 1.86-1.59 (6H, m).; 13C-NMR (CDCl3) δ: 25.6, 34.1, 42.2, 56.3, 58.3, 121.8, 123.7, 126.7, 126.8, 127.6, 128.1, 128.4, 132.0, 132.7, 135.5, 136.1, 137.0, 137.1, 145.5, 146.5, 149.5, 155.9. (Z) -4'-(2-hydroxyethanesulfonyl) -4-cyclo-pentyl-5- (pyridin-2-yl-2-vinyl) -1,1'-biphenyl (D25) 1 H-NMR (CDCl 3 ) δ: 8.58 (1H, d, J = 4.1 Hz), 7.89 (2H, dt, J = 8.7, 1.8 Hz), 7.55 (2H, dd, J = 8.7, 1.8 Hz), 7.51 (1H, dd, J = 8.2, 2.3 Hz), 7.46 (1H, d, J = 7.8 Hz), 7.37-7.33 (2H, m), 7.07 (2H, dt, J = 12.4, 3.0 Hz), 6.92 (1H, d, J = 8.2) Hz), 6.85 (1H, d, J = 12.4 Hz), 4.01 (2H, q, J = 5.5 Hz), 3.36 (2H, td, J = 4.1, 2.0 Hz), 3.29 (1H, t, J = 8.5) Hz), 3.04 (1H, s), 2.02 (2H, tt, J = 7.6, 4.0 Hz), 1.86-1.59 (6H, m) .; 13 C-NMR (CDCl 3 ) δ: 25.6, 34.1, 42.2, 56.3, 58.3, 121.8, 123.7, 126.7, 126.8, 127.6, 128.1, 128.4, 132.0, 132.7, 135.5, 136.1, 137.0, 137.1, 145.5, 146.5, 149.5, 155.9.

(5)Ｅ１～Ｅ２５の合成
Ｅ１～Ｅ２５の合成は下記Simons-Smith合成法により合成した。 (5) Synthesis of E1 to E25 The synthesis of E1 to E25 was synthesized by the following Simmons-Smith synthesis method.

Figure 0007060775000164
Figure 0007060775000164

合成したE1～E25のNMRを下記に示す。 The synthesized NMR of E1 to E25 is shown below.

cis-4'-(2-hydroxyethanesulfonyl)-3-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E1) 1H-NMR (CDCl3) δ: 8.50 (1H, dq, J= 4.9, 0.9 Hz), 7.98 (2H, dt, J = 8.8, 1.9 Hz), 7.77 (2H, dt, J = 8.4, 1.9 Hz), 7.57 (1H, td, J = 7.6, 1.9 Hz), 7.41 (3H, td, J = 3.3, 1.8 Hz), 7.21 (2H, tt, J = 4.4, 1.5 Hz), 7.09 (1H, ddd, J = 7.4, 4.8, 1.1 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.41-3.39 (2H, m), 3.04 (1H, s), 2.62 (1H, ddd, J = 9.5, 5.3, 3.4 Hz), 2.34 (1H, ddd, J = 9.2, 5.0, 3.6 Hz), 1.82 (1H, ddd, J = 9.6, 4.9, 3.9 Hz), 1.54 (1H, ddd, J= 9.7, 5.1, 3.6 Hz).; 13C-NMR (CDCl3) δ: 18.9, 28.0, 29.5, 56.3, 58.3, 120.8, 122.0, 124.9, 125.3, 126.0, 128.1, 128.5, 129.2, 136.0, 137.3, 139.1, 143.3, 147.1, 149.4, 160.7. cis-4'-(2-hydroxyethanesulfonyl) -3- (2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E1) 1 H-NMR (CDCl 3 ) δ: 8.50 (1H, dq) , J = 4.9, 0.9 Hz), 7.98 (2H, dt, J = 8.8, 1.9 Hz), 7.77 (2H, dt, J = 8.4, 1.9 Hz), 7.57 (1H, td, J = 7.6, 1.9 Hz) , 7.41 (3H, td, J = 3.3, 1.8 Hz), 7.21 (2H, tt, J = 4.4, 1.5 Hz), 7.09 (1H, ddd, J = 7.4, 4.8, 1.1 Hz), 4.04 (2H, t) , J = 5.3 Hz), 3.41-3.39 (2H, m), 3.04 (1H, s), 2.62 (1H, ddd, J = 9.5, 5.3, 3.4 Hz), 2.34 (1H, ddd, J = 9.2, 5.0 , 3.6 Hz), 1.82 (1H, ddd, J = 9.6, 4.9, 3.9 Hz), 1.54 (1H, ddd, J = 9.7, 5.1, 3.6 Hz) .; 13 C-NMR (CDCl 3 ) δ: 18.9, 28.0, 29.5, 56.3, 58.3, 120.8, 122.0, 124.9, 125.3, 126.0, 128.1, 128.5, 129.2, 136.0, 137.3, 139.1, 143.3, 147.1, 149.4, 160.7.

cis-2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E2) 1H-NMR (CDCl3) δ: 8.49 (1H, d, J= 4.6 Hz), 8.00 (2H, d, J = 8.2 Hz), 7.76 (2H, d, J = 6.9 Hz), 7.59-7.55 (1H, m), 7.24-7.08 (5H, m), 4.05 (2H, s), 3.40 (2H, t, J = 5.3 Hz), 2.87 (1H, s), 2.62-2.57 (1H, m), 2.30-2.25 (1H, m), 1.78 (1H, td, J= 9.8, 5.3 Hz), 1.47 (1H, dt, J = 10.2, 4.4 Hz).; 13C-NMR (CDCl3) δ: 18.8, 27.1, 29.3, 56.4, 58.3, 116.3 (d, J = 23.0 Hz), 120.9, 122.0, 126.7 (d, J = 13.4 Hz), 127.7 (d, J = 7.7 Hz), 128.1, 128.2 (d, J = 2.9 Hz), 130.0 (d, J = 2.9 Hz), 136.0, 137.7,138.8 (d, J = 3.8 Hz), 141.9, 149.4, 159.3, 160.5. cis-2-fluoro-4'-(2-hydroxyethanesulfonyl) -5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E2) 1 H-NMR (CDCl 3 ) δ: 8.49 (1H, d, J = 4.6 Hz), 8.00 (2H, d, J = 8.2 Hz), 7.76 (2H, d, J = 6.9 Hz), 7.59-7.55 (1H, m), 7.24-7.08 (5H, m), 4.05 (2H, s), 3.40 (2H, t, J = 5.3 Hz), 2.87 (1H, s), 2.62-2.57 (1H, m), 2.30-2.25 (1H, m), 1.78 (1H) , td, J = 9.8, 5.3 Hz), 1.47 (1H, dt, J = 10.2, 4.4 Hz).; 13 C-NMR (CDCl 3 ) δ: 18.8, 27.1, 29.3, 56.4, 58.3, 116.3 (d, J = 23.0 Hz), 120.9, 122.0, 126.7 (d, J = 13.4 Hz), 127.7 (d, J = 7.7 Hz), 128.1, 128.2 (d, J = 2.9 Hz), 130.0 (d, J = 2.9 Hz) ), 136.0, 137.7, 138.8 (d, J = 3.8 Hz), 141.9, 149.4, 159.3, 160.5.

cis-4'-(2-hydroxyethanesulfonyl)-3-(2-(6-methylpyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E3) 1H-NMR (CDCl3) δ: 7.98 (2H, d, J = 8.2 Hz), 7.78 (2H, dd, J = 6.9, 1.8 Hz), 7.43 (4H, dt, J = 17.6, 5.2 Hz), 7.22-7.20 (1H, m), 6.95 (2H, t, J = 7.1 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m), 2.96 (1H, s), 2.59-2.55 (1H, m), 2.51 (3H, s), 2.34 (1H, ddd, J = 9.2, 5.0, 3.7 Hz), 1.79 (1H, dt, J = 9.6, 4.6 Hz), 1.50 (1H, ddd, J = 9.5, 4.9, 3.8 Hz).; 13C-NMR (CDCl3) δ: 18.9, 24.6, 27.8, 29.7, 56.3, 58.3, 118.1, 120.3, 124.8, 125.3, 126.0, 128.1, 128.4, 129.1, 136.2, 137.2, 139.0, 143.5, 147.2, 158.0, 160.0. cis-4'-(2-hydroxyethanesulfonyl) -3- (2- (6-methylpyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E3) 1 H-NMR (CDCl 3 ) δ: 7.98 (2H) , d, J = 8.2 Hz), 7.78 (2H, dd, J = 6.9, 1.8 Hz), 7.43 (4H, dt, J = 17.6, 5.2 Hz), 7.22-7.20 (1H, m), 6.95 (2H, t, J = 7.1 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m), 2.96 (1H, s), 2.59-2.55 (1H, m), 2.51 (3H, s) ), 2.34 (1H, ddd, J = 9.2, 5.0, 3.7 Hz), 1.79 (1H, dt, J = 9.6, 4.6 Hz), 1.50 (1H, ddd, J = 9.5, 4.9, 3.8 Hz) .; 13 C-NMR (CDCl 3 ) δ: 18.9, 24.6, 27.8, 29.7, 56.3, 58.3, 118.1, 120.3, 124.8, 125.3, 126.0, 128.1, 128.4, 129.1, 136.2, 137.2, 139.0, 143.5, 147.2, 158.0, 160.0 ..

cis-2-fluoro-4'-(2-hydroxyethanesulfonyl)-5-(2-(6-methylpyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E4) 1H-NMR (CDCl3) δ: 7.98 (2H, d, J = 8.2 Hz), 7.78 (2H, dd, J = 6.9, 1.8 Hz), 7.43 (4H, dt, J = 17.6, 5.2 Hz), 7.22-7.20 (1H, m), 6.95 (2H, t, J = 7.1 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m), 2.96 (1H, s), 2.59-2.55 (1H, m), 2.51 (3H, s), 2.34 (1H, ddd, J = 9.2, 5.0, 3.7 Hz), 1.79 (1H, dt, J = 9.6, 4.6 Hz), 1.50 (1H, ddd, J = 9.5, 4.9, 3.8 Hz).; 13C-NMR (CDCl3) δ: 18.7, 24.5, 26.9, 29.4, 56.3, 58.3, 116.2 (d, J = 22.0 Hz), 118.0, 120.3, 126.6 (d, J = 13.4 Hz), 127.6 (d, J = 8.6 Hz), 128.1 (d, J = 10.5 Hz), 128.2 (d, J = 2.9 Hz), 129.9 (d, J = 2.9 Hz), 136.2, 137.7, 138.9 (d, J= 3.8 Hz), 141.9 (d, J = 1.9 Hz), 156.7, 158.0, 159.2, 159.8.; 19F-NMR (CDCl3) δ: -22.0. cis-2-fluoro-4'-(2-hydroxyethanesulfonyl) -5-(2- (6-methylpyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E4) 1 H-NMR (CDCl 3 ) δ : 7.98 (2H, d, J = 8.2 Hz), 7.78 (2H, dd, J = 6.9, 1.8 Hz), 7.43 (4H, dt, J = 17.6, 5.2 Hz), 7.22-7.20 (1H, m), 6.95 (2H, t, J = 7.1 Hz), 4.04 (2H, t, J = 5.5 Hz), 3.41-3.38 (2H, m), 2.96 (1H, s), 2.59-2.55 (1H, m), 2.51 (3H, s), 2.34 (1H, ddd, J = 9.2, 5.0, 3.7 Hz), 1.79 (1H, dt, J = 9.6, 4.6 Hz), 1.50 (1H, ddd, J = 9.5, 4.9, 3.8 Hz) ).; 13 C-NMR (CDCl 3 ) δ: 18.7, 24.5, 26.9, 29.4, 56.3, 58.3, 116.2 (d, J = 22.0 Hz), 118.0, 120.3, 126.6 (d, J = 13.4 Hz), 127.6 (d, J = 8.6 Hz), 128.1 (d, J = 10.5 Hz), 128.2 (d, J = 2.9 Hz), 129.9 (d, J = 2.9 Hz), 136.2, 137.7, 138.9 (d, J = 3.8) Hz), 141.9 (d, J = 1.9 Hz), 156.7, 158.0, 159.2, 159.8 .; 19 F-NMR (CDCl 3 ) δ: -22.0.

cis-3-tert-butyl-4'-(2-hydroxyethanesulfonyl)-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E5) 1H-NMR (CDCl3) δ: 8.50 (1H, d, J= 4.6 Hz), 7.98 (2H, t, J = 4.4 Hz), 7.77 (2H, dd, J = 6.9, 1.8 Hz), 7.56 (1H, td, J = 7.8, 1.8 Hz), 7.42 (1H, t, J = 1.8 Hz), 7.29 (1H, t, J = 1.8 Hz), 7.21 (1H, t, J = 3.9 Hz), 7.17 (1H, t, J= 1.6 Hz), 7.08 (1H, ddd, J = 7.4, 4.9, 1.3 Hz), 4.04 (2H, d, J = 5.0 Hz), 3.41-3.38 (2H, m), 2.96 (1H, s), 2.64-2.60 (1H, m), 2.37-2.32 (1H, m), 1.81 (1H, dt, J = 9.6, 4.4 Hz), 1.55 (1H, ddd, J = 9.7, 4.9, 3.5 Hz), 1.37 (9H, s).; 13C-NMR (CDCl3) δ: 19.0, 28.2, 29.5, 31.3, 34.9, 56.4, 58.4, 120.8, 121.9, 122.0, 122.3, 124.0, 128.2, 128.4, 136.0, 137.2, 139.0, 142.9, 147.9, 149.4, 152.2, 160.8. cis-3-tert-butyl-4'-(2-hydroxyethanesulfonyl) -5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E5) 1 H-NMR (CDCl 3 ) δ : 8.50 (1H, d, J = 4.6 Hz), 7.98 (2H, t, J = 4.4 Hz), 7.77 (2H, dd, J = 6.9, 1.8 Hz), 7.56 (1H, td, J = 7.8, 1.8) Hz), 7.42 (1H, t, J = 1.8 Hz), 7.29 (1H, t, J = 1.8 Hz), 7.21 (1H, t, J = 3.9 Hz), 7.17 (1H, t, J = 1.6 Hz) , 7.08 (1H, ddd, J = 7.4, 4.9, 1.3 Hz), 4.04 (2H, d, J = 5.0 Hz), 3.41-3.38 (2H, m), 2.96 (1H, s), 2.64-2.60 (1H) , m), 2.37-2.32 (1H, m), 1.81 (1H, dt, J = 9.6, 4.4 Hz), 1.55 (1H, ddd, J = 9.7, 4.9, 3.5 Hz), 1.37 (9H, s). 13 C-NMR (CDCl 3 ) δ: 19.0, 28.2, 29.5, 31.3, 34.9, 56.4, 58.4, 120.8, 121.9, 122.0, 122.3, 124.0, 128.2, 128.4, 136.0, 137.2, 139.0, 142.9, 147.9, 149.4 , 152.2, 160.8.

cis-4'-(2-hydroxyethanesulfonyl)-3-methyl-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E6) 1H-NMR (CDCl3) δ: 8.38-8.37 (1H, m), 7.90 (2H, t, J = 4.4 Hz), 7.53 (2H, dd, J = 6.9, 1.8 Hz), 7.40 (1H, td, J = 7.8, 1.8 Hz), 7.07 (1H, s), 6.98-6.92 (4H, m), 4.02 (2H, t, J = 5.5 Hz), 3.38 (2H, dd, J = 6.9, 4.1 Hz), 3.32 (1H, s), 2.72 (1H, td, J = 8.9, 6.4 Hz), 2.61 (1H, dd, J = 15.8, 8.9 Hz), 2.27 (3H, s), 1.85 (1H, q, J = 6.1 Hz), 1.55 (1H, td, J = 8.6, 5.3 Hz).; 13C-NMR (CDCl3) δ: 11.0, 21.2, 25.3, 26.2, 56.2, 58.3, 120.7, 123.4, 125.1, 125.6, 127.8, 128.2, 128.6, 130.6, 132.0, 135.5, 137.0, 138.0, 138.8, 147.2, 148.5, 158.0. cis-4'-(2-hydroxyethanesulfonyl) -3-methyl-5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E6) 1 H-NMR (CDCl 3 ) δ: 8.38 -8.37 (1H, m), 7.90 (2H, t, J = 4.4 Hz), 7.53 (2H, dd, J = 6.9, 1.8 Hz), 7.40 (1H, td, J = 7.8, 1.8 Hz), 7.07 ( 1H, s), 6.98-6.92 (4H, m), 4.02 (2H, t, J = 5.5 Hz), 3.38 (2H, dd, J = 6.9, 4.1 Hz), 3.32 (1H, s), 2.72 (1H) , td, J = 8.9, 6.4 Hz), 2.61 (1H, dd, J = 15.8, 8.9 Hz), 2.27 (3H, s), 1.85 (1H, q, J = 6.1 Hz), 1.55 (1H, td, J = 8.6, 5.3 Hz) .; 13 C-NMR (CDCl 3 ) δ: 11.0, 21.2, 25.3, 26.2, 56.2, 58.3, 120.7, 123.4, 125.1, 125.6, 127.8, 128.2, 128.6, 130.6, 132.0, 135.5 , 137.0, 138.0, 138.8, 147.2, 148.5, 158.0.

cis-4'-(2-hydroxyethanesulfonyl)-4-methyl-3-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E8) 1H-NMR (CDCl3) δ: 8.29-8.27 (1H, m), 7.95 (2H, dt, J = 8.5, 2.1 Hz), 7.67 (2H, dt, J = 8.7, 1.8 Hz), 7.36 (1H, d, J = 1.8 Hz), 7.31 (1H, td, J = 7.8, 1.8 Hz), 7.25 (1H, dd, J = 8.2, 2.7 Hz), 7.05 (1H, d, J = 8.2 Hz), 6.90 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.76 (1H, d, J = 8.2 Hz), 4.04 (2H, s), 3.39 (2H, td, J = 4.1, 2.1 Hz), 3.06 (1H, s), 2.78 (1H, td, J= 8.7, 6.0 Hz), 2.58 (1H, q, J = 8.2 Hz), 2.25 (3H, s), 1.89 (1H, dd, J= 12.4, 5.5 Hz), 1.60 (1H, td, J = 8.5, 5.2 Hz).; 13C-NMR (CDCl3) δ: 11.1, 19.4, 25.0, 25.3, 56.4, 58.4, 120.5,121.7, 125.0, 127.7, 128.4, 128.4, 130.0, 135.3, 135.6, 136.5, 136.8, 139.6, 147.2, 148.4, 158.4. cis-4'-(2-hydroxyethanesulfonyl) -4-methyl-3-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E8) 1 H-NMR (CDCl 3 ) δ: 8.29 -8.27 (1H, m), 7.95 (2H, dt, J = 8.5, 2.1 Hz), 7.67 (2H, dt, J = 8.7, 1.8 Hz), 7.36 (1H, d, J = 1.8 Hz), 7.31 ( 1H, td, J = 7.8, 1.8 Hz), 7.25 (1H, dd, J = 8.2, 2.7 Hz), 7.05 (1H, d, J = 8.2 Hz), 6.90 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.76 (1H, d, J = 8.2 Hz), 4.04 (2H, s), 3.39 (2H, td, J = 4.1, 2.1 Hz), 3.06 (1H, s), 2.78 (1H, td, J = 8.7, 6.0 Hz), 2.58 (1H, q, J = 8.2 Hz), 2.25 (3H, s), 1.89 (1H, dd, J = 12.4, 5.5 Hz), 1.60 (1H, td, J = 8.5) , 5.2 Hz) .; 13 C-NMR (CDCl 3 ) δ: 11.1, 19.4, 25.0, 25.3, 56.4, 58.4, 120.5, 121.7, 125.0, 127.7, 128.4, 128.4, 130.0, 135.3, 135.6, 136.5, 136.8, 139.6, 147.2, 148.4, 158.4.

cis-4'-(2-hydroxyethanesulfonyl)-3-(2-(3-methylpyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E9) 1H-NMR (CDCl3) δ: 8.35 (1H, t, J = 2.5 Hz), 7.99 (2H, dt, J = 8.5, 1.9 Hz), 7.79 (2H, dt, J = 8.7, 1.8 Hz), 7.41 (4H, tt, J = 8.2, 1.7 Hz), 7.27-7.23 (1H, m), 7.00 (1H, dd, J = 7.6, 4.8 Hz), 4.05 (2H, q, J = 5.5 Hz), 3.40 (2H, td, J = 4.1, 2.0 Hz), 2.78 (1H, t, J= 6.2 Hz), 2.64 (1H, ddd, J = 9.5, 5.2, 3.8 Hz), 2.41 (1H, td, J= 5.5, 4.7 Hz), 2.39 (1H, s), 1.89 (1H, ddd, J = 9.4, 4.8, 3.9 Hz), 1.52 (1H, ddd, J = 9.5, 4.9, 3.5 Hz).; 13C-NMR (CDCl3) δ: 12.5, 25.6, 26.2, 27.4, 58.4, 64.0, 120.5, 125.4, 126.1, 128.2, 131.6, 132.7, 137.0, 139.0, 146.7. cis-4'-(2-hydroxyethanesulfonyl) -3- (2- (3-methylpyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E9) 1 H-NMR (CDCl 3 ) δ: 8.35 (1H) , t, J = 2.5 Hz), 7.99 (2H, dt, J = 8.5, 1.9 Hz), 7.79 (2H, dt, J = 8.7, 1.8 Hz), 7.41 (4H, tt, J = 8.2, 1.7 Hz) , 7.27-7.23 (1H, m), 7.00 (1H, dd, J = 7.6, 4.8 Hz), 4.05 (2H, q, J = 5.5 Hz), 3.40 (2H, td, J = 4.1, 2.0 Hz), 2.78 (1H, t, J = 6.2 Hz), 2.64 (1H, ddd, J = 9.5, 5.2, 3.8 Hz), 2.41 (1H, td, J = 5.5, 4.7 Hz), 2.39 (1H, s), 1.89 (1H, ddd, J = 9.4, 4.8, 3.9 Hz), 1.52 (1H, ddd, J = 9.5, 4.9, 3.5 Hz) .; 13 C-NMR (CDCl 3 ) δ: 12.5, 25.6, 26.2, 27.4, 58.4, 64.0, 120.5, 125.4, 126.1, 128.2, 131.6, 132.7, 137.0, 139.0, 146.7.

cis-4'-(2-hydroxyethanesulfonyl)-3-(2-(6-methylpyridin-2-yl)cyclopropyl)-4-methyl-1,1'-biphenyl (E10) 1H-NMR (CDCl3) δ: 7.95 (2H, dt, J = 8.7, 2.1 Hz), 7.68 (2H, dt, J = 8.7, 1.8 Hz), 7.40 (1H, d, J = 1.8 Hz), 7.24 (1H, dd, J = 7.8, 1.8 Hz), 7.17 (1H, t, J = 7.8 Hz), 7.04 (1H, d, J = 7.8 Hz), 6.74 (1H, d, J = 7.3 Hz), 6.48 (1H, d, J = 7.8 Hz), 4.05-4.03 (2H, m), 3.42-3.39 (2H, m), 3.30 (1H, br s), 2.74 (1H, td, J = 8.7, 6.0 Hz), 2.54 (1H, q, J = 8.2 Hz), 2.30 (3H, s), 2.22 (3H, s), 1.86 (1H, dd, J= 12.4, 6.0 Hz), 1.56 (1H, td, J = 8.6, 5.2 Hz).; 13C-NMR (CDCl3) δ: 11.2, 19.4, 24.2, 24.9, 25.2, 56.2, 58.3, 118.2, 119.8, 124.8, 127.6, 128.3, 128.5, 129.9, 135.4, 135.5, 136.7,136.8, 139.6, 147.2, 156.7, 157.6. cis-4'-(2-hydroxyethanesulfonyl) -3- (2- (6-methylpyridin-2-yl) cyclopropyl) -4-methyl-1,1'-biphenyl (E10) 1 H-NMR (CDCl 3 ) δ : 7.95 (2H, dt, J = 8.7, 2.1 Hz), 7.68 (2H, dt, J = 8.7, 1.8 Hz), 7.40 (1H, d, J = 1.8 Hz), 7.24 (1H, dd, J = 7.8) , 1.8 Hz), 7.17 (1H, t, J = 7.8 Hz), 7.04 (1H, d, J = 7.8 Hz), 6.74 (1H, d, J = 7.3 Hz), 6.48 (1H, d, J = 7.8) Hz), 4.05-4.03 (2H, m), 3.42-3.39 (2H, m), 3.30 (1H, br s), 2.74 (1H, td, J = 8.7, 6.0 Hz), 2.54 (1H, q, J = 8.2 Hz), 2.30 (3H, s), 2.22 (3H, s), 1.86 (1H, dd, J = 12.4, 6.0 Hz), 1.56 (1H, td, J = 8.6, 5.2 Hz).; 13 C -NMR (CDCl 3 ) δ: 11.2, 19.4, 24.2, 24.9, 25.2, 56.2, 58.3, 118.2, 119.8, 124.8, 127.6, 128.3, 128.5, 129.9, 135.4, 135.5, 136.7, 136.8, 139.6, 147.2, 156.7, 157.6.

cis-4'-(2-hydroxyethanesulfonyl)-3-(2-(3-methylpyridin-2-yl)cyclopropyl)-4-methyl-1,1'-biphenyl (E11) 1H-NMR (CDCl3) δ: 8.36 (1H, d, J = 4.6 Hz), 8.00-7.97 (2H, m), 7.78 (2H, dt, J = 8.7, 1.8 Hz), 7.40 (3H, td, J = 7.3, 6.4 Hz), 7.27 (2H, t, J= 5.3 Hz), 7.01 (1H, dd, J = 7.6, 4.8 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.40 (2H, td, J = 4.1, 2.0 Hz), 2.93 (1H, s), 2.71 (1H, dt, J= 9.8, 4.4 Hz), 2.42 (3H, s), 2.38 (3H, s), 2.30 (1H, dt, J = 9.3, 4.2 Hz), 1.81-1.76 (1H, m), 1.54 (1H, ddd, J = 9.3, 5.4, 3.1 Hz).; 13C-NMR (CDCl3) δ: 16.8, 19.0, 19.5, 23.7, 25.7, 56.4, 58.4, 120.4, 124.8, 125.0, 127.8, 128.5, 130.5, 130.6, 136.5, 137.0, 137.1, 139.1, 141.3, 146.8, 147.3, 159.0. cis-4'-(2-hydroxyethanesulfonyl) -3- (2- (3-methylpyridin-2-yl) cyclopropyl) -4-methyl-1,1'-biphenyl (E11) 1 H-NMR (CDCl 3 ) δ : 8.36 (1H, d, J = 4.6 Hz), 8.00-7.97 (2H, m), 7.78 (2H, dt, J = 8.7, 1.8 Hz), 7.40 (3H, td, J = 7.3, 6.4 Hz), 7.27 (2H, t, J = 5.3 Hz), 7.01 (1H, dd, J = 7.6, 4.8 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.40 (2H, td, J = 4.1, 2.0 Hz) ), 2.93 (1H, s), 2.71 (1H, dt, J = 9.8, 4.4 Hz), 2.42 (3H, s), 2.38 (3H, s), 2.30 (1H, dt, J = 9.3, 4.2 Hz) , 1.81-1.76 (1H, m), 1.54 (1H, ddd, J = 9.3, 5.4, 3.1 Hz) .; 13 C-NMR (CDCl 3 ) δ: 16.8, 19.0, 19.5, 23.7, 25.7, 56.4, 58.4 , 120.4, 124.8, 125.0, 127.8, 128.5, 130.5, 130.6, 136.5, 137.0, 137.1, 139.1, 141.3, 146.8, 147.3, 159.0.

cis-4'-(2-hydroxyethanesulfonyl)-2-methyl-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E12) 1H-NMR (CDCl3) δ: 8.36 (1H, dd, J= 4.9, 0.9 Hz), 7.91 (2H, dt, J = 8.3, 1.8 Hz), 7.41 (1H, td, J = 7.7, 1.8 Hz), 7.30-7.27 (2H, m), 7.02-6.97 (3H, m), 6.90 (1H, d, J = 8.0 Hz), 6.79 (1H, s), 4.05 (2H, t, J = 5.7 Hz), 3.67 (1H, s), 3.43-3.40 (2H, m), 2.68 (1H, td, J = 8.8, 6.4 Hz), 2.62-2.55 (1H, m), 2.10 (3H, s), 1.77 (1H, dd, J = 11.8, 6.3 Hz), 1.51 (1H, td, J = 8.5, 5.4 Hz).; 13C-NMR (CDCl3) δ: 10.8, 19.7, 24.9, 26.0, 56.1, 58.2, 120.6, 123.3, 127.6, 129.1, 130.0, 130.0, 130.0, 132.2, 135.5, 135.6, 137.0, 138.7, 148.0, 148.4, 158.0. cis-4'-(2-hydroxyethanesulfonyl) -2-methyl-5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E12) 1 H-NMR (CDCl 3 ) δ: 8.36 (1H, dd, J = 4.9, 0.9 Hz), 7.91 (2H, dt, J = 8.3, 1.8 Hz), 7.41 (1H, td, J = 7.7, 1.8 Hz), 7.30-7.27 (2H, m), 7.02-6.97 (3H, m), 6.90 (1H, d, J = 8.0 Hz), 6.79 (1H, s), 4.05 (2H, t, J = 5.7 Hz), 3.67 (1H, s), 3.43-3.40 (2H, m), 2.68 (1H, td, J = 8.8, 6.4 Hz), 2.62-2.55 (1H, m), 2.10 (3H, s), 1.77 (1H, dd, J = 11.8, 6.3 Hz), 1.51 (1H, td, J = 8.5, 5.4 Hz) .; 13 C-NMR (CDCl 3 ) δ: 10.8, 19.7, 24.9, 26.0, 56.1, 58.2, 120.6, 123.3, 127.6, 129.1, 130.0, 130.0, 130.0 , 132.2, 135.5, 135.6, 137.0, 138.7, 148.0, 148.4, 158.0.

cis-4'-(2-hydroxyethanesulfonyl)-4-propyl-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E14) 1H-NMR (CDCl3) δ: 8.29 (1H, dt, J= 5.0, 0.9 Hz), 7.94 (2H, dt, J = 8.6, 1.9 Hz), 7.66 (2H, dt, J = 8.6, 1.9 Hz), 7.35-7.27 (4H, m), 7.08 (1H, d, J = 8.0 Hz), 6.91 (1H, ddd, J = 7.4, 5.0, 1.0 Hz), 6.75 (1H, d, J = 8.0 Hz), 4.04 (2H, t, J = 5.4 Hz), 3.40 (2H, dt, J = 9.6, 3.7 Hz), 3.13 (1H, d, J= 3.1 Hz), 2.81-2.60 (3H, m), 2.54-2.46 (1H, m), 1.90 (1H, dd, J = 12.6, 5.7 Hz), 1.66-1.57 (2H, m), 1.45 (1H, ddt, J = 16.9, 9.7, 3.6 Hz), 0.94 (3H, t, J = 7.3 Hz).; 13C-NMR (CDCl3) δ: 11.4, 14.1, 23.0, 24.4, 25.8, 34.3, 56.3, 58.3, 120.5, 121.9, 125.0, 127.7, 128.3, 128.5, 129.0, 135.3, 135.3, 135.9, 136.7, 143.8, 147.2, 148.3, 158.4. cis-4'-(2-hydroxyethanesulfonyl) -4-propyl-5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E14) 1 H-NMR (CDCl 3 ) δ: 8.29 (1H, dt, J = 5.0, 0.9 Hz), 7.94 (2H, dt, J = 8.6, 1.9 Hz), 7.66 (2H, dt, J = 8.6, 1.9 Hz), 7.35-7.27 (4H, m), 7.08 (1H, d, J = 8.0 Hz), 6.91 (1H, ddd, J = 7.4, 5.0, 1.0 Hz), 6.75 (1H, d, J = 8.0 Hz), 4.04 (2H, t, J = 5.4 Hz) ), 3.40 (2H, dt, J = 9.6, 3.7 Hz), 3.13 (1H, d, J = 3.1 Hz), 2.81-2.60 (3H, m), 2.54-2.46 (1H, m), 1.90 (1H, dd, J = 12.6, 5.7 Hz), 1.66-1.57 (2H, m), 1.45 (1H, ddt, J = 16.9, 9.7, 3.6 Hz), 0.94 (3H, t, J = 7.3 Hz) .; 13 C -NMR (CDCl 3 ) δ: 11.4, 14.1, 23.0, 24.4, 25.8, 34.3, 56.3, 58.3, 120.5, 121.9, 125.0, 127.7, 128.3, 128.5, 129.0, 135.3, 135.3, 135.9, 136.7, 143.8, 147.2, 148.3, 158.4.

cis-4'-(2-hydroxyethanesulfonyl)-4-pentyl-3-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E16) 1H-NMR (CDCl3) δ: 1H-NMR (CDCl3) δ: 8.28 (1H, dq, J = 5.0, 0.9 Hz), 7.94 (2H, dt, J = 8.5, 2.0 Hz), 7.65 (2H, dt, J = 8.8, 1.9 Hz), 7.35 (1H, d, J = 1.9 Hz), 7.29 (2H, tt, J = 10.3, 3.4 Hz), 7.08 (1H, t, J = 4.0 Hz), 6.89 (1H, ddd, J = 7.3, 4.9, 1.0 Hz), 6.74 (1H, t, J = 4.0 Hz), 4.04-4.02 (2H, m), 3.39 (2H, td, J = 4.1, 2.3 Hz), 3.25 (1H, br s), 2.80-2.69 (2H, m), 2.63 (1H, dd, J = 16.0, 8.8 Hz), 2.55-2.48 (1H, m), 1.92-1.88 (1H, m), 1.63-1.51 (2H, m), 1.45-1.27 (5H, m), 0.90 (3H, dd, J= 9.0, 5.1 Hz).; 13C-NMR (CDCl3) δ: 11.4, 14.0, 22.5, 24.4, 25.8, 29.7, 31.8, 32.2, 56.3, 58.4, 120.5, 121.9, 125.0, 127.6, 128.3, 128.6, 128.9, 135.2, 135.3, 135.8, 136.9, 144.0, 147.1, 148.3,158.4. cis-4'-(2-hydroxyethanesulfonyl) -4-pentyl-3- (2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E16) 1 H-NMR (CDCl 3 ) δ: 1 H-NMR (CDCl 3 ) δ: 8.28 (1H, dq, J = 5.0, 0.9 Hz), 7.94 (2H, dt, J = 8.5, 2.0 Hz), 7.65 (2H, dt, J = 8.8, 1.9 Hz) , 7.35 (1H, d, J = 1.9 Hz), 7.29 (2H, tt, J = 10.3, 3.4 Hz), 7.08 (1H, t, J = 4.0 Hz), 6.89 (1H, ddd, J = 7.3, 4.9) , 1.0 Hz), 6.74 (1H, t, J = 4.0 Hz), 4.04-4.02 (2H, m), 3.39 (2H, td, J = 4.1, 2.3 Hz), 3.25 (1H, br s), 2.80- 2.69 (2H, m), 2.63 (1H, dd, J = 16.0, 8.8 Hz), 2.55-2.48 (1H, m), 1.92-1.88 (1H, m), 1.63-1.51 (2H, m), 1.45- 1.27 (5H, m), 0.90 (3H, dd, J = 9.0, 5.1 Hz) .; 13 C-NMR (CDCl 3 ) δ: 11.4, 14.0, 22.5, 24.4, 25.8, 29.7, 31.8, 32.2, 56.3, 58.4, 120.5, 121.9, 125.0, 127.6, 128.3, 128.6, 128.9, 135.2, 135.3, 135.8, 136.9, 144.0, 147.1, 148.3, 158.4.

cis-4'-(2-hydroxyethanesulfonyl)-4-iso-propyl-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E17) 1H-NMR (CDCl3) δ: 8.30-8.29 (1H, m), 7.96 (2H, dt, J = 8.5, 2.1 Hz), 7.72 (2H, dt, J = 8.5, 1.9 Hz), 7.46 (1H, d, J = 1.4 Hz), 7.36 (1H, dd, J = 8.0, 2.1 Hz), 7.31-7.27 (1H, m), 7.16 (1H, d, J = 8.2 Hz), 6.89 (1H, ddd, J = 7.6, 4.8, 1.1 Hz), 6.65 (1H, d, J = 7.8 Hz), 4.04 (2H, q, J = 5.5 Hz), 3.39 (3H, ddd, J = 12.6, 7.8, 5.3 Hz), 2.81 (2H, dq, J = 20.0, 5.6 Hz), 2.64 (1H, dd, J = 16.0, 8.7 Hz), 1.87 (1H, dd, J = 12.4, 6.0 Hz), 1.63 (2H, td, J = 8.5, 5.2 Hz), 1.18 (3H, d, J = 6.9 Hz), 0.79 (3H, d, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 11.7, 22.5, 24.2, 24.6, 25.9, 28.6, 56.5, 58.4, 120.5, 121.4, 125.5, 125.6, 127.8, 128.4, 129.1, 135.0,135.2, 135.4, 136.8, 147.3, 148.5, 150.2, 158.5. cis-4'-(2-hydroxyethanesulfonyl) -4-iso-propyl-5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E17) 1 H-NMR (CDCl 3 ) δ : 8.30-8.29 (1H, m), 7.96 (2H, dt, J = 8.5, 2.1 Hz), 7.72 (2H, dt, J = 8.5, 1.9 Hz), 7.46 (1H, d, J = 1.4 Hz), 7.36 (1H, dd, J = 8.0, 2.1 Hz), 7.31-7.27 (1H, m), 7.16 (1H, d, J = 8.2 Hz), 6.89 (1H, ddd, J = 7.6, 4.8, 1.1 Hz) , 6.65 (1H, d, J = 7.8 Hz), 4.04 (2H, q, J = 5.5 Hz), 3.39 (3H, ddd, J = 12.6, 7.8, 5.3 Hz), 2.81 (2H, dq, J = 20.0) , 5.6 Hz), 2.64 (1H, dd, J = 16.0, 8.7 Hz), 1.87 (1H, dd, J = 12.4, 6.0 Hz), 1.63 (2H, td, J = 8.5, 5.2 Hz), 1.18 (3H) , d, J = 6.9 Hz), 0.79 (3H, d, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 11.7, 22.5, 24.2, 24.6, 25.9, 28.6, 56.5, 58.4, 120.5, 121.4, 125.5, 125.6, 127.8, 128.4, 129.1, 135.0, 135.2, 135.4, 136.8, 147.3, 148.5, 150.2, 158.5.

cis-4'-(2-hydroxyethanesulfonyl)-3-(2-(3-methylpyridin-2-yl)cyclopropyl)-4-propyl-1,1'-biphenyl (E19) 1H-NMR (CDCl3) δ: 8.37 (1H, d, J = 3.2 Hz), 7.99 (2H, dd, J = 6.7, 1.9 Hz), 7.80-7.78 (2H, m), 7.41 (2H, tt, J = 4.9, 1.8 Hz), 7.35 (1H, d, J = 1.9 Hz), 7.28 (1H, d, J = 7.8 Hz), 7.01 (1H, dd, J = 7.5, 4.9 Hz), 4.05 (2H, s), 3.41-3.39 (2H, m), 2.79 (2H, dt, J = 9.7, 4.3 Hz), 2.72 (2H, dd, J = 11.1, 4.6 Hz), 2.40 (3H, s), 2.30 (1H, dt, J= 9.4, 4.3 Hz), 1.80-1.76 (1H, m), 1.57 (2H, ddd, J = 10.8, 6.8, 4.4 Hz), 0.86 (3H, t, J = 7.3 Hz).; 13C-NMR (CDCl3) δ: 14.1, 17.0, 18.9, 23.6, 24.4, 25.1, 34.9, 56.5, 58.4, 120.4, 124.6, 125.0, 127.9, 128.5, 129.8, 130.7, 136.5, 137.0, 137.1, 140.8, 143.4, 146.8, 147.4, 159.0. cis-4'-(2-hydroxyethanesulfonyl) -3- (2- (3-methylpyridin-2-yl) cyclopropyl) -4-propyl-1,1'-biphenyl (E19) 1 H-NMR (CDCl 3 ) δ : 8.37 (1H, d, J = 3.2 Hz), 7.99 (2H, dd, J = 6.7, 1.9 Hz), 7.80-7.78 (2H, m), 7.41 (2H, tt, J = 4.9, 1.8 Hz), 7.35 (1H, d, J = 1.9 Hz), 7.28 (1H, d, J = 7.8 Hz), 7.01 (1H, dd, J = 7.5, 4.9 Hz), 4.05 (2H, s), 3.41-3.39 (2H) , m), 2.79 (2H, dt, J = 9.7, 4.3 Hz), 2.72 (2H, dd, J = 11.1, 4.6 Hz), 2.40 (3H, s), 2.30 (1H, dt, J = 9.4, 4.3 Hz), 1.80-1.76 (1H, m), 1.57 (2H, ddd, J = 10.8, 6.8, 4.4 Hz), 0.86 (3H, t, J = 7.3 Hz) .; 13 C-NMR (CDCl 3 ) δ : 14.1, 17.0, 18.9, 23.6, 24.4, 25.1, 34.9, 56.5, 58.4, 120.4, 124.6, 125.0, 127.9, 128.5, 129.8, 130.7, 136.5, 137.0, 137.1, 140.8, 143.4, 146.8, 147.4, 159.0.

cis-4'-(2-hydroxyethanesulfonyl)-3-(2-(3-penthylpyridin-2-yl)cyclopropyl)-4-propyl-1,1'-biphenyl (E21) 1H-NMR (CDCl3) δ: 8.37 (1H, dd, J = 4.8, 1.7 Hz), 7.99 (2H, dt, J = 8.6, 2.0 Hz), 7.79 (2H, dt, J = 8.6, 1.9 Hz), 7.41 (2H, dd, J = 7.8, 1.9 Hz), 7.31 (2H, dd, J = 26.8, 4.9 Hz), 7.02 (1H, dd, J = 7.6, 4.8 Hz), 4.05 (2H, s), 3.41-3.39 (2H, m), 2.85 (1H, s), 2.81 (1H, dt, J= 9.7, 4.4 Hz), 2.75-2.66 (4H, m), 2.34 (1H, dt, J = 9.4, 4.3 Hz), 1.80-1.75 (1H, m), 1.65-1.52 (5H, m), 1.34-1.22 (4H, m), 0.84 (6H, dt, J= 17.3, 7.2 Hz).; 13C-NMR (CDCl3) δ: 13.9, 14.1, 17.3, 22.5, 23.7, 24.1, 25.1, 30.2, 31.6, 32.5, 34.9, 56.4, 58.4, 120.4, 124.5, 124.9, 127.9, 128.5, 129.8, 135.3, 136.3, 136.5, 137.0, 140.9, 143.4, 146.8, 147.3, 158.4. cis-4'-(2-hydroxyethanesulfonyl) -3- (2- (3-penthylpyridin-2-yl) cyclopropyl) -4-propyl-1,1'-biphenyl (E21) 1 H-NMR (CDCl 3 ) δ : 8.37 (1H, dd, J = 4.8, 1.7 Hz), 7.99 (2H, dt, J = 8.6, 2.0 Hz), 7.79 (2H, dt, J = 8.6, 1.9 Hz), 7.41 (2H, dd, J) = 7.8, 1.9 Hz), 7.31 (2H, dd, J = 26.8, 4.9 Hz), 7.02 (1H, dd, J = 7.6, 4.8 Hz), 4.05 (2H, s), 3.41-3.39 (2H, m) , 2.85 (1H, s), 2.81 (1H, dt, J = 9.7, 4.4 Hz), 2.75-2.66 (4H, m), 2.34 (1H, dt, J = 9.4, 4.3 Hz), 1.80-1.75 (1H) , m), 1.65-1.52 (5H, m), 1.34-1.22 (4H, m), 0.84 (6H, dt, J = 17.3, 7.2 Hz) .; 13 C-NMR (CDCl 3 ) δ: 13.9, 14.1 , 17.3, 22.5, 23.7, 24.1, 25.1, 30.2, 31.6, 32.5, 34.9, 56.4, 58.4, 120.4, 124.5, 124.9, 127.9, 128.5, 129.8, 135.3, 136.3, 136.5, 137.0, 140.9, 143.4, 146.8, 147.3 , 158.4.

cis-4-heptyl-4'-(2-hydroxyethanesulfonyl)-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E22) 1H-NMR (CDCl3) δ: 8.28 (1H, d, J= 4.6 Hz), 7.94 (2H, d, J = 8.2 Hz), 7.65 (2H, d, J = 8.7 Hz), 7.31 (4H, tt, J = 11.9, 4.5 Hz), 7.08 (1H, d, J = 7.8 Hz), 6.90 (1H, dd, J = 6.9, 5.0 Hz), 6.74 (1H, d, J = 8.2 Hz), 4.03 (2H, s), 3.39 (3H, dd, J = 10.3, 4.8 Hz), 2.80-2.69 (2H, m), 2.63 (1H, dd, J= 16.3, 8.5 Hz), 2.55-2.48 (1H, m), 1.89 (1H, q, J = 6.0 Hz), 1.63-1.52 (2H, m), 1.35 (9H, tt, J = 25.4, 7.9 Hz), 0.89 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 11.4, 14.1, 22.6, 24.4, 25.7, 29.2, 29.6, 30.0, 31.7, 32.3, 56.2, 58.3, 120.5, 121.9, 125.0, 127.6, 128.3, 128.6, 128.9, 135.3, 135.3, 135.7, 136.8, 144.0, 147.1, 148.3, 158.4. cis-4-heptyl-4'-(2-hydroxyethanesulfonyl) -5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E22) 1 H-NMR (CDCl 3 ) δ: 8.28 (1H, d, J = 4.6 Hz), 7.94 (2H, d, J = 8.2 Hz), 7.65 (2H, d, J = 8.7 Hz), 7.31 (4H, tt, J = 11.9, 4.5 Hz), 7.08 (1H, d, J = 7.8 Hz), 6.90 (1H, dd, J = 6.9, 5.0 Hz), 6.74 (1H, d, J = 8.2 Hz), 4.03 (2H, s), 3.39 (3H, dd, J = 10.3, 4.8 Hz), 2.80-2.69 (2H, m), 2.63 (1H, dd, J = 16.3, 8.5 Hz), 2.55-2.48 (1H, m), 1.89 (1H, q, J = 6.0 Hz) ), 1.63-1.52 (2H, m), 1.35 (9H, tt, J = 25.4, 7.9 Hz), 0.89 (3H, t, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 11.4, 14.1, 22.6, 24.4, 25.7, 29.2, 29.6, 30.0, 31.7, 32.3, 56.2, 58.3, 120.5, 121.9, 125.0, 127.6, 128.3, 128.6, 128.9, 135.3, 135.3, 135.7, 136.8, 144.0, 147.1, 148.3, 158.4.

cis-4'-(2-hydroxyethanesulfonyl)-4-octyl-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E23) 1H-NMR (CDCl3) δ: 8.29 (1H, dt, J= 4.3, 1.5 Hz), 7.96-7.93 (2H, m), 7.66 (2H, dt, J = 8.7, 1.8 Hz), 7.35-7.27 (3H, m), 7.08 (1H, d, J = 8.2 Hz), 6.90 (1H, ddd, J = 7.3, 5.0, 0.9 Hz), 6.75 (1H, d, J = 7.8 Hz), 4.03 (2H, s), 3.41-3.38 (2H, m), 3.18 (1H, s), 2.80-2.69 (2H, m), 2.63 (1H, q, J = 8.2 Hz), 2.55-2.48 (1H, m), 1.90 (1H, dd, J = 12.4, 6.0 Hz), 1.58 (2H, dtd, J= 23.2, 7.9, 4.7 Hz), 1.43-1.24 (11H, m), 0.89 (3H, t, J = 6.9 Hz).; 13C-NMR (CDCl3) δ: 11.4, 14.1, 22.6, 24.4, 25.8, 29.2, 29.5, 29.7, 30.0, 31.8, 32.3, 56.3, 58.3, 120.5, 121.9, 125.0, 127.7, 128.3, 128.6, 129.0, 135.2, 135.3, 135.8, 136.7, 144.1, 147.1, 148.3, 158.4. cis-4'-(2-hydroxyethanesulfonyl) -4-octyl-5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E23) 1 H-NMR (CDCl 3 ) δ: 8.29 (1H, dt, J = 4.3, 1.5 Hz), 7.96-7.93 (2H, m), 7.66 (2H, dt, J = 8.7, 1.8 Hz), 7.35-7.27 (3H, m), 7.08 (1H, d) , J = 8.2 Hz), 6.90 (1H, ddd, J = 7.3, 5.0, 0.9 Hz), 6.75 (1H, d, J = 7.8 Hz), 4.03 (2H, s), 3.41-3.38 (2H, m) , 3.18 (1H, s), 2.80-2.69 (2H, m), 2.63 (1H, q, J = 8.2 Hz), 2.55-2.48 (1H, m), 1.90 (1H, dd, J = 12.4, 6.0 Hz) ), 1.58 (2H, dtd, J = 23.2, 7.9, 4.7 Hz), 1.43-1.24 (11H, m), 0.89 (3H, t, J = 6.9 Hz) .; 13 C-NMR (CDCl 3 ) δ: 11.4, 14.1, 22.6, 24.4, 25.8, 29.2, 29.5, 29.7, 30.0, 31.8, 32.3, 56.3, 58.3, 120.5, 121.9, 125.0, 127.7, 128.3, 128.6, 129.0, 135.2, 135.3, 135.8, 136.7, 144.1, 147.1, 148.3, 158.4.

cis-4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl)-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E24) 1H-NMR (CDCl3) δ: 8.28-8.27 (1H, m), 7.96 (2H, dt, J = 8.7, 1.8 Hz), 7.73 (2H, dt, J = 8.5, 2.1 Hz), 7.49 (1H, d, J = 1.8 Hz), 7.36 (1H, dd, J = 8.0, 2.1 Hz), 7.29 (2H, td, J = 7.7, 1.7 Hz), 7.12 (1H, d, J = 8.2 Hz), 6.90 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.65 (1H, d, J = 8.2 Hz), 4.04 (2H, d, J = 5.0 Hz), 3.41-3.38 (2H, m), 3.03 (1H, s), 2.94 (1H, t, J = 11.7 Hz), 2.80 (1H, td, J = 8.7, 6.0 Hz), 2.62 (1H, dd, J = 16.0, 8.7 Hz), 1.86-1.61 (7H, m), 1.49-1.17 (5H, m), 0.67 (1H, d, J = 12.8 Hz).; 13C-NMR (CDCl3) δ: 11.8, 24.7, 25.9, 26.2, 26.7, 27.1, 32.7, 34.7, 39.4, 56.4, 58.4, 120.5, 121.3, 125.5, 126.2, 127.7, 128.4, 129.3, 135.1, 135.3, 136.7, 147.2, 148.4, 149.1, 158.5. cis-4-cyclo-hexyl-4'-(2-hydroxyethanesulfonyl) -5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E24) 1 H-NMR (CDCl 3 ) δ : 8.28-8.27 (1H, m), 7.96 (2H, dt, J = 8.7, 1.8 Hz), 7.73 (2H, dt, J = 8.5, 2.1 Hz), 7.49 (1H, d, J = 1.8 Hz), 7.36 (1H, dd, J = 8.0, 2.1 Hz), 7.29 (2H, td, J = 7.7, 1.7 Hz), 7.12 (1H, d, J = 8.2 Hz), 6.90 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.65 (1H, d, J = 8.2 Hz), 4.04 (2H, d, J = 5.0 Hz), 3.41-3.38 (2H, m), 3.03 (1H, s), 2.94 (1H, t, J = 11.7 Hz), 2.80 (1H, td, J = 8.7, 6.0 Hz), 2.62 (1H, dd, J = 16.0, 8.7 Hz), 1.86-1.61 (7H, m), 1.49-1.17 (5H) , m), 0.67 (1H, d, J = 12.8 Hz) .; 13 C-NMR (CDCl 3 ) δ: 11.8, 24.7, 25.9, 26.2, 26.7, 27.1, 32.7, 34.7, 39.4, 56.4, 58.4, 120.5 , 121.3, 125.5, 126.2, 127.7, 128.4, 129.3, 135.1, 135.3, 136.7, 147.2, 148.4, 149.1, 158.5.

cis-4'-(2-hydroxyethanesulfonyl)-4-cyclo-pentyl-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (E25) 1H-NMR (CDCl3) δ: 8.29 (1H, t, J = 2.3 Hz), 7.95 (2H, t, J = 4.1 Hz), 7.70 (2H, t, J = 4.4 Hz), 7.44 (1H, d, J = 1.8 Hz), 7.35 (1H, dd, J = 8.0, 2.1 Hz), 7.31-7.27 (1H, m), 7.17 (1H, d, J = 8.2 Hz), 6.90 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.62 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.45-3.39 (3H, m), 3.34 (1H, d, J = 16.9 Hz), 2.78 (1H, td, J = 8.7, 6.0 Hz), 2.66 (1H, q, J = 8.2 Hz), 2.12-2.04 (1H, m), 1.85-1.61 (6H, m), 1.46-1.23 (3H, m).; 13C-NMR (CDCl3) δ: 12.0, 24.8, 25.8, 25.8, 25.9, 33.8, 35.2, 40.6, 56.3, 58.3, 120.5, 121.3, 125.5, 126.1, 127.6, 128.3, 128.4, 128.8, 132.0, 135.2, 135.2, 135.7, 136.8, 147.0, 148.1, 148.3, 158.6. cis-4'-(2-hydroxyethanesulfonyl) -4-cyclo-pentyl-5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (E25) 1 H-NMR (CDCl 3 ) δ : 8.29 (1H, t, J = 2.3 Hz), 7.95 (2H, t, J = 4.1 Hz), 7.70 (2H, t, J = 4.4 Hz), 7.44 (1H, d, J = 1.8 Hz), 7.35 (1H, dd, J = 8.0, 2.1 Hz), 7.31-7.27 (1H, m), 7.17 (1H, d, J = 8.2 Hz), 6.90 (1H, ddd, J = 7.4, 4.9, 1.0 Hz), 6.62 (1H, d, J = 7.8 Hz), 4.04 (2H, t, J = 5.3 Hz), 3.45-3.39 (3H, m), 3.34 (1H, d, J = 16.9 Hz), 2.78 (1H, td) , J = 8.7, 6.0 Hz), 2.66 (1H, q, J = 8.2 Hz), 2.12-2.04 (1H, m), 1.85-1.61 (6H, m), 1.46-1.23 (3H, m) .; 13 C-NMR (CDCl 3 ) δ: 12.0, 24.8, 25.8, 25.8, 25.9, 33.8, 35.2, 40.6, 56.3, 58.3, 120.5, 121.3, 125.5, 126.1, 127.6, 128.3, 128.4, 128.8, 132.0, 135.2, 135.2 , 135.7, 136.8, 147.0, 148.1, 148.3, 158.6.

(6)Ｆ１～Ｆ２５の合成
Ｆ１～Ｆ２５の合成は下記Simons-Smith合成法により合成した。 (6) Synthesis of F1 to F25 F1 to F25 were synthesized by the following Simmons-Smith synthesis method.

Figure 0007060775000165
Figure 0007060775000165

合成したF1～F25においてF14のNMRを下記に示す。 The NMR of F14 in the synthesized F1 to F25 is shown below.

trans-4'-(2-hydroxyethanesulfonyl)-4-propyl-5-(2-(pyridin-2-yl)cyclopropyl)-1,1'-biphenyl (F14) 1H-NMR (CDCl3) δ: 8.52 (1H, dq, J= 4.9, 0.9 Hz), 7.98 (2H, dt, J = 8.6, 2.0 Hz), 7.78 (2H, dt, J = 8.6, 2.0 Hz), 7.59 (1H, td, J = 7.6, 1.9 Hz), 7.40 (1H, dd, J = 7.9, 2.0 Hz), 7.33-7.26 (3H, m), 7.23 (1H, dt, J = 7.8, 1.0 Hz), 7.10 (1H, ddd, J = 7.4, 5.0, 1.1 Hz), 4.04 (2H, s), 3.41-3.38 (2H, m), 2.84 (1H, s), 2.70 (3H, dt, J = 12.6, 5.4 Hz), 2.21 (1H, dt, J = 9.3, 4.3 Hz), 1.77 (1H, ddd, J = 9.3, 4.9, 4.0 Hz), 1.65-1.55 (4H, m), 0.86 (3H, t, J = 7.3 Hz).; 13C-NMR (CDCl3) δ: 14.1, 17.1, 23.7, 25.8, 28.0, 35.0, 56.4, 58.4, 120.7, 121.9, 124.7, 125.1, 127.9, 128.5, 129.8, 136.0, 136.5, 137.0, 140.4, 143.4, 147.3, 149.5, 161.0. trans-4'-(2-hydroxyethanesulfonyl) -4-propyl-5-(2- (pyridin-2-yl) cyclopropyl) -1,1'-biphenyl (F14) 1 H-NMR (CDCl 3 ) δ: 8.52 (1H, dq, J = 4.9, 0.9 Hz), 7.98 (2H, dt, J = 8.6, 2.0 Hz), 7.78 (2H, dt, J = 8.6, 2.0 Hz), 7.59 (1H, td, J = 7.6) , 1.9 Hz), 7.40 (1H, dd, J = 7.9, 2.0 Hz), 7.33-7.26 (3H, m), 7.23 (1H, dt, J = 7.8, 1.0 Hz), 7.10 (1H, ddd, J = 7.4, 5.0, 1.1 Hz), 4.04 (2H, s), 3.41-3.38 (2H, m), 2.84 (1H, s), 2.70 (3H, dt, J = 12.6, 5.4 Hz), 2.21 (1H, dt) , J = 9.3, 4.3 Hz), 1.77 (1H, ddd, J = 9.3, 4.9, 4.0 Hz), 1.65-1.55 (4H, m), 0.86 (3H, t, J = 7.3 Hz) .; 13 C- NMR (CDCl 3 ) δ: 14.1, 17.1, 23.7, 25.8, 28.0, 35.0, 56.4, 58.4, 120.7, 121.9, 124.7, 125.1, 127.9, 128.5, 129.8, 136.0, 136.5, 137.0, 140.4, 143.4, 147.3, 149.5 , 161.0.

(7)CERT結合親和性、及び、CERT機能阻害性
本実施例にかかる化合物について、表面プラズモン共鳴法(SPR法)によりCERTとの結合親和性を調べた。光学異性体が存在する化合物ではラセミ体について測定した。結合の強さは解離定数Kd（dissociation constant、単位：μM）で示され、この値が小さいほど結合が強いことを示す。Kdは下記表1及び表２において各セル中の上段に記載する。 (7) CERT binding affinity and CERT function inhibitory properties The binding affinity of the compound according to this example was investigated by the surface plasmon resonance method (SPR method). For compounds with optical isomers, racemates were measured. The strength of the bond is indicated by the dissociation constant Kd (dissociation constant, unit: μM), and the smaller this value is, the stronger the bond is. Kd is listed in the upper part of each cell in Tables 1 and 2 below.

本実施例にかかる化合物について、無血清培養HeLa細胞における放射性セリンを用いたSM(スフィンゴミエリン)代謝標識率により、CERT機能阻害性を調べた。光学異性体が存在する化合物ではラセミ体について測定した。SM代謝標識率は、化合物無添加時に対する１μM化合物存在時の相対値により調べた。SM代謝標識率は、下記表1及び表２において各セル中の下段に記載する。 The CERT function inhibitory effect of the compound according to this example was examined by the SM (sphingomyelin) metabolism labeling rate using radioactive serine in serum-free cultured HeLa cells. For compounds with optical isomers, racemates were measured. The SM metabolism labeling rate was examined by the relative value in the presence of 1 μM compound with respect to the case where no compound was added. The SM metabolism labeling rate is shown in the lower part of each cell in Tables 1 and 2 below.

Figure 0007060775000166
Figure 0007060775000166

Figure 0007060775000167
Figure 0007060775000167

表１及び表２の結果から、E16及びE25が、優れたCERT結合親和性及びCERT機能阻害性を示すことが判明した。 From the results in Tables 1 and 2, it was found that E16 and E25 show excellent CERT binding affinity and CERT function inhibitory property.

(8)異性体
E16及びE25は、優れたCERT結合親和性及びCERT機能阻害性を示したが、それらについて光学異性体ごとのCERT結合親和性及びCERT機能阻害性を調べた。光学異性体の分離は株式会社ダイセルのCHIRALPAK IA-3を使用した。 (8) Isomer
E16 and E25 showed excellent CERT binding affinity and CERT function inhibitory properties, and the CERT binding affinity and CERT function inhibitory properties of each optical isomer were investigated for them. For the separation of optical isomers, CHIRALPAK IA-3 of Daicel Corporation was used.

E16の一方の異性体であるE16-A(1S,2R)は下記である。 One isomer of E16, E16-A (1S, 2R), is as follows.

Figure 0007060775000168
Figure 0007060775000168

E16の他方の異性体であるE16-B(1R,2S)は下記である。 The other isomer of E16, E16-B (1R, 2S), is:

Figure 0007060775000169
Figure 0007060775000169

E25の一方の異性体であるE25-A(1S,2R)は下記である。 One isomer of E25, E25-A (1S, 2R), is as follows.

Figure 0007060775000170
Figure 0007060775000170

E25の他方の異性体であるE25-B(1R,2S)は下記である。 The other isomer of E25, E25-B (1R, 2S), is:

Figure 0007060775000171
Figure 0007060775000171

各光学異性体の旋光(optical rotation)は下記であった。
(+)-E16-A: HPLC (hexane / iPrOH = 6/4, flow rate = 1.0 ml / min, UV detection at 254 nm) tR= 6.7 min.; [a]D 33.3 = +109.0 (c 1.32, CHCl3)
(-)-E16-B: HPLC (hexane / iPrOH = 6/4, flow rate = 1.0 ml / min, UV detection at 254 nm) tR= 9.5 min.; [a]D 33.8 = -106.5 (c 1.26, CHCl3)
(+)-E25-A: HPLC (hexane / iPrOH = 6/4, flow rate = 1.0 ml / min, UV detection at 254 nm) tR= 8.4 min.; [a]D 34.3 = +102.9 (c 1.32, CHCl3)
(-)-E25-B: HPLC (hexane / iPrOH = 6/4, flow rate = 1.0 ml / min, UV detection at 254 nm) tR= 13.3 min.; [a]D 34.2 = -102.3 (c 1.12, CHCl3) The optical rotation of each optical isomer was as follows.
(+)-E16-A: HPLC (hexane / iPrOH = 6/4, flow rate = 1.0 ml / min, UV detection at 254 nm) t R = 6.7 min .; [a] D 33.3 = +109.0 (c 1.32) , CHCl 3 )
(-)-E16-B: HPLC (hexane / iPrOH = 6/4, flow rate = 1.0 ml / min, UV detection at 254 nm) t R = 9.5 min .; [a] D 33.8 = -106.5 (c 1.26) , CHCl 3 )
(+)-E25-A: HPLC (hexane / iPrOH = 6/4, flow rate = 1.0 ml / min, UV detection at 254 nm) t R = 8.4 min .; [a] D 34.3 = +102.9 (c 1.32) , CHCl 3 )
(-)-E25-B: HPLC (hexane / iPrOH = 6/4, flow rate = 1.0 ml / min, UV detection at 254 nm) t R = 13.3 min .; [a] D 34.2 = -102.3 (c 1.12) , CHCl 3 )

SPR法によりCERTとの結合親和性を調べた。結果を下記表３に示す。 The binding affinity with CERT was investigated by the SPR method. The results are shown in Table 3 below.

Figure 0007060775000172
Figure 0007060775000172

10％血清含有培地中にて代謝標識解析を行い、CERT機能阻害性を調べた。結果を下記表４に示す。 Metabolic labeling analysis was performed in a medium containing 10% serum to investigate CERT function inhibition. The results are shown in Table 4 below.

Figure 0007060775000173
Figure 0007060775000173

更に、E16及びE25について光学異性体ごとに、10%血清培養HeLa細胞における放射性セリンを用いたSM代謝標識率により、CERT機能阻害性を調べた。結果を図１及び表５に示す。 Furthermore, for each optical isomer of E16 and E25, the CERT function inhibition was examined by the SM metabolic labeling rate using radioactive serine in 10% serum-cultured HeLa cells. The results are shown in FIGS. 1 and 5.

Figure 0007060775000174
Figure 0007060775000174

上記結果から、E16-A及びE-25Aは、優れたCERT結合親和性及びCERT機能阻害性を示すことが判明した。 From the above results, it was found that E16-A and E-25A show excellent CERT binding affinity and CERT function inhibitory property.

抗ウイルス剤、抗がん剤として利用できる。 It can be used as an antiviral agent and an anticancer agent.

Claims (7)

下記構造式(I)からなる新規化合物
Figure 0007060775000175
 （ここで、結合基－Ｘ－は、－Ｃ≡Ｃ－、－ＣＨ２ＣＨ２－、cis－ＣＨ＝ＣＨ－、trans－ＣＨ＝ＣＨ－、cis－シクロプロピル－、又は、trans－シクロプロピル－であり、Ｒ１、Ｒ２、Ｒ３、Ｒ４、及びＲ５は、各々独立して、水素原子、ハロゲン原子、１以上のハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ８アルキル基、又は、ＯＲ６（Ｒ６は、水素原子、又は、ハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ６アルキル基である。）である。）。 A novel compound having the following structural formula (I)
Figure 0007060775000175
 (Here, the binding group -X- is -C≡C-, -CH 2 CH 2- , cis-CH = CH-, trans-CH = CH-, cis-cyclopropyl-, or trans-cyclopropyl. -, And R 1 , R 2 , R 3 , R 4 , and R 5 are linear or branched chains that may independently have a hydrogen atom, a halogen atom, or one or more halogen atoms. C1-C8 alkyl group or OR 6 (R 6 is a linear or branched C1-C6 alkyl group which may have a hydrogen atom or a halogen atom). .. 下記構造式を有する請求項１記載の新規化合物
Figure 0007060775000176
 （ここで、Ｒ１、Ｒ２、Ｒ３、Ｒ４、及びＲ５は、各々独立して、水素原子、ハロゲン原子、１以上のハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ８アルキル基、又は、ＯＲ６（Ｒ６は、水素原子、又は、ハロゲン原子を有していてもよい直鎖若しくは分枝鎖のＣ１－Ｃ６アルキル基である。）である。）。 The novel compound according to claim 1, which has the following structural formula.
Figure 0007060775000176
 (Here, R 1 , R 2 , R 3 , R 4 , and R 5 are linear or branched chains that may independently have a hydrogen atom, a halogen atom, and one or more halogen atoms, respectively. C1-C8 alkyl group or OR 6 (R 6 is a linear or branched C1-C6 alkyl group which may have a hydrogen atom or a halogen atom). .. 下記構造式を有する請求項１記載の新規化合物
Figure 0007060775000177
 （ここで、結合基－Ｘ－は、－Ｃ≡Ｃ－、－ＣＨ２ＣＨ２－、cis－ＣＨ＝ＣＨ－、trans－ＣＨ＝ＣＨ－、cis－シクロプロピル－、又は、trans－シクロプロピル－である。）。 The novel compound according to claim 1, which has the following structural formula.
Figure 0007060775000177
 (Here, the linking group -X- is -C≡C-, -CH 2 CH 2- , cis-CH = CH-, trans-CH = CH-, cis-cyclopropyl-, or trans-cyclopropyl. -.). 下記構造式を有する請求項３記載の新規化合物。
Figure 0007060775000178
 The novel compound according to claim 3, which has the following structural formula.
Figure 0007060775000178
 請求項１乃至４の何れか一項に記載の化合物を含む、CERTのSTARTドメインに結合してCERT機能を阻害する、CERT機能阻害剤。 A CERT function inhibitor that binds to the START domain of CERT and inhibits CERT function, which comprises the compound according to any one of claims 1 to 4 . 医薬的に有効量の請求項１乃至５の何れか一項に記載の化合物を含みがんを治療又は予防するための医薬組成物。 A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to any one of claims 1 to 5 for treating or preventing cancer. 医薬的に有効量の請求項１乃至５の何れか一項に記載の化合物を含み感染症を治療又は予防するための医薬組成物。 A pharmaceutical composition comprising a pharmaceutically effective amount of the compound according to any one of claims 1 to 5 for treating or preventing an infectious disease.
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