TWI619695B - 蛋白酪胺酸磷酸酶ｓｈｐ－１之增效劑 - Google Patents

蛋白酪胺酸磷酸酶ｓｈｐ－１之增效劑 Download PDF

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TWI619695B
TWI619695B TW105128510A TW105128510A TWI619695B TW I619695 B TWI619695 B TW I619695B TW 105128510 A TW105128510 A TW 105128510A TW 105128510 A TW105128510 A TW 105128510A TW I619695 B TWI619695 B TW I619695B
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nmr
urea
cyanophenoxy
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陳昆鋒
蕭崇瑋
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蕭崇瑋
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Abstract

本發明說明書揭露數個新穎化合物。這些新穎化合物具有SHP-1增效劑活性，能夠用於治療癌症。

Description

蛋白酪胺酸磷酸酶SHP-1之增效劑
本發明係關於一種具有含Src同源區-2的蛋白酪胺酸磷酸酶-1(SHP-1)增效劑活性的新穎化合物，以及使用該化合物的治療方法。
SHP-1，一種帶有二個Src同源區2(SH2)結構區域的蛋白酪胺酸磷酸酶，是一種對不同的細胞內信號分子的調節劑，例如信號轉導因子和轉錄激活因子3(STAT3)、KIT、CD22、CD5、CD72、SHPS-1、TIMP(金屬蛋白酶)、CDK2、p27、SRC、ZAP70、介白素10(IL-10)、NF-κB、Lck、3BP2、Lyn，以及細胞週期素D1。
STAT3是一種藉由調控目標基因的表現來調節發炎、細胞生長和存活的轉錄因子。它在許多癌症中作為構成型活化的致癌基因，包含肝臟、肺臟、頭部及頸部、前列腺、乳房部位的癌症、以及骨髓癌與白血病。SHP-1是STAT3活性的一個關鍵調節因子。從機制的觀點來看，SHP-1顯現蛋白磷酸酶的活性，進而減少磷酸化-STAT3(P-STAT3)的濃度，並隨後阻斷P-STAT3的二聚合作用。因此，目標基因的表現，例如由STAT3轉錄的細胞週期素D1以及生存素，明顯地減少。
此外，SHP-1蛋白以及SHP-1 mRNA的研究顯示，在大部份的癌細胞中SHP-1的表現量低；且在癌細胞中SHP-1基因表現的增加導致細 胞生長的抑制，這意味著SHP-1基因具有腫瘤抑制因子的作用。從藥物開發的觀點來看，開發一種可以減少P-STAT3以及增加SHP-1活性或表現量的小分子是一個很有前景的癌症治療方向。
SHP-1在骨骼再成型中也扮演一個重要的角色，骨骼再成型是一種造骨細胞形成骨骼以及噬骨細胞再吸收骨骼的過程。SHP-1的功能喪失造成噬骨細胞活性的增加且最終導致骨質疏鬆症。因此，增強SHP-1的活性可能是對骨質疏鬆症患者的一種治療方向。
此外，SHP-1的增加對於多發性硬化症患者的巨噬細胞而言是有益的。
因此，本說明書中提供一些新穎化合物。這些新穎化合物具有SHP-1增效活性的潛力，可用於癌症治療。
由本說明書之一實施例，提供具有如下所示化學結構式之化合物I：
在該化合物I的化學結構式中，N為0或1。
X為N或C-R1。
R1為H或Cl。
R2為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該 烷基例如為CH3或CH2CH3。
R3為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R2與R3亦可共同形成一二價飽和或未飽和基團，例如。
Ar為一未取代或經取代的伸苯基(phenylene group)或一伸萘 基(naphthalenylene group)。該伸苯基例如可為或。該 伸萘基例如可為。
R4為H、一鹵素或一烷基。該鹵素例如為F或Cl。該烷基例如為CH3或CH2CH3。
R5為H、一鹵素、一烷基、一烷氧基、或一羥基。該鹵素例如為F或Cl。該烷基例如為CH3或CH2CH3。
R6為H或一羥基。
R5與R6亦可共同形成一二價飽和或未飽和基團，例如
R7為一未取代或經取代的芳香基。R7例如為一經取代的苯 基、一經取代的、、或 。該經取代的苯基例如可為、、 、、、或。該經取代的 基團例如可為、、
由本說明書之另一實施例，提供具有如下所示化學結構式之化合物II：
在化合物II之化學結構式中，R2與R3為H。
Ar為一經取代之芳香基，例如或。
由本說明書之另一實施例，提供一化合物III，其具有如下所示之化學結構式：
在化合物III的化學結構式中，R8為一鹵烷基或一經取代的苯 氧基(C6H5O-)。該鹵烷基例如為CF3。該經取代的苯氧基例如為
R9為H、一鹵素、或一烷基。該鹵素例如為Cl。該烷基例如為CH3或CH2CH3。
X為、、、或。
由本說明書之另一實施例，提供一化合物IV，其具有如下所示之化學結構式：
在化合物IV的化學結構式中，R8為一經取代的苯氧基 (C6H5O-)，例如。
R9為H。
此外，本發明亦提供包含一有效量之上述任一化合物的醫藥組成物。
根據本發明之實施例，該醫藥組成物可進一步包含一醫藥上可接受之載體。
以上的概括性描述及以下之實施方式係為示例，係用以闡明本發明所請之範圍。
根據本說明書之揭露，該作為SHP-1增效劑之新穎化合物用於治療關於降低SHP-1之基因表現或生物活性之疾病或症狀是有效的，該些疾病或症狀例如癌症(如肝癌、白血病、肺癌、乳癌、腎癌、胸腺癌、頭頸癌)、硬化及骨質疏鬆症。這些化合物亦對於激酶抑制劑具有抗性的病患提供一種新的治療選擇。即使激酶抑制劑存在的情況下，這些腫瘤在治療後會於激酶產生突變且以持續磷酸化活化形式存在。
因此，對化療具有抗性的病患而言，腫瘤抑制因子的提升，特別是SHP-1的量與活性上調以抑制激酶的活化突變形式，是一種具有前景的治療方向。換言之，本發明之化合物透過一種新的標靶機制(非依賴激酶)，提供替代的治療選擇，該選擇對於傳統癌症醫療具有抗性的患者是有幫助的。
通用化學結構
根據本說明書一實施例，提供具有下列化學結構式之化合物I：
在化合物I之化學結構式中，N為0或1。
X為N或C-R1。
R1為H或Cl。
R2為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R3為H、一鹵素、或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R2與R3亦可共同形成一二價飽和或不飽和基團，例如。
Ar為一未取代或經取代的伸苯基(phenylene group)或一伸萘 基(naphthalenylene group)。該經取代的伸苯基例如可為或 。該伸萘基例如可為。
R4為H、一鹵素或一烷基。該鹵素例如為F或Cl。該烷基例如為CH3或CH2CH3。
R5為H、一鹵素、一烷基、一烷氧基、或一羥基。該鹵素例如為F或Cl。該烷基例如為CH3或CH2CH3。
R6為H或一羥基。
R5與R6亦可共同形成一二價飽和或未飽和基團，例如
R7為一未取代或經取代的芳香基。R7例如為一經取代的苯 基、一經取代的、、或 。該經取代的苯基例如可為、、 、、、或。該經取代的 基團例如可為、、
由本說明書之另一實施例，提供一化合物II，其具有下列化學結構式。
在化合物II的化學結構式中，R2與R3為H。
Ar為一經取代的芳香基，例如或。
由本說明書之另一實施例，提供一化合物III，其具有下列化學結構式。
在化合物III的化學結構式中，R8為一鹵烷基或一經取代的苯 氧基(C6H5O-)。該鹵烷基例如為CF3。該經取代的苯氧基例如為
R9為H、一鹵素、或一烷基。該鹵素例如為Cl。該烷基例如為CH3或CH2CH3。
X為、、、或。
由本說明書之另一實施例，提供一化合物IV，其具有如下所示之化學結構式。
在化合物IV的化學結構式中，R8為一經取代的苯氧基 (C6H5O-)，例如。
R9為H。
化學合成
在合成流程I的第一步驟中，化合物A與化合物B在叔丁醇鉀(t-BuOK)的存在下耦合以生成中間產物C。在這個步驟中，首先在4℃將叔丁醇鉀加入化合物B的DMSO溶液。接著，將化合物A加入這個反應混合物中。將所得的反應混合物在室溫下攪拌5分鐘然後以微波加熱至150℃維持20分鐘。在反應混合物冷卻至室溫後，加入冰水以中止反應。以乙酸乙酯萃取(3 x 100mL)該反應化合物。以飽和食鹽水(brine)洗滌所收集的有機相，並以無水硫酸鎂乾燥後，最後進行過濾。將過濾物濃縮並層析純化而得到中間物C。
在步驟2中，該中間物C與該胺類R7NH2與三光氣 (triphosgene)反應以得到最終化合物I。在這個步驟中，乾燥的胺類R之THF溶液與三乙胺於冰浴條件下慢慢地加入乾燥的三光氣THF溶液。將混合物於60℃、氮氣環境下攪拌30分鐘。在溫度降至室溫後，將中間物C的乾燥THF溶液於冰浴條件下緩慢加入該混合物，並加熱至60℃維持整夜。將最終溶液進行過濾以去除鹽，且將該過濾液濃縮以進行層析。層析純化後得到化合物I。
在合成流程I：N為0或1。
X為N或C-R1。
R1為H或Cl。
R2為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R3為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R2與R3亦可共同形成一二價飽和或未飽和基團，例如。
Ar為一未取代或經取代的伸苯基(phenylene group)或一伸萘 基(naphthalenylene group)。該伸苯基例如可為或。該 伸萘基例如可為。
R4為H、一鹵素或一烷基。該鹵素例如為F或Cl。該烷基例如為CH3或CH2CH3。
R5為H、一鹵素、一烷基、一烷氧基、或一羥基。該鹵素例 如為F或Cl。該烷基例如為CH3或CH2CH3。
R6為H或一羥基。
R5與R6亦可共同形成一二價飽和或未飽和基團，例如
R7為一未取代或經取代的芳香基。R7例如為一經取代的苯 基、一經取代的、、或 。該經取代的苯基可為、、 、、、或。該經取代的 基團例如可為、、
實施例1：合成流程I中Ar為
在合成流程1中，n為0。
X為N或C-R1。
R1為H或Cl。
R2為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R3為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R2與R3亦可共同形成一二價飽和或未飽和基團，例如。
R4為H、一鹵素或一烷基。該鹵素例如為F或Cl。該烷基例如為CH3或CH2CH3。
R5為H、一鹵素、一烷基、一烷氧基、或一羥基。該鹵素例如為F或Cl。該烷基例如為CH3或CH2CH3。
R6為H或一羥基。
R5與R6亦可共同形成一二價飽和或未飽和的基團，例如
R7為一未取代或經取代的芳香基。例如，R7為一經取代的苯 基，或一經取代的、或。該經取代的苯 基可為、、、、、或 。該經取代的例如可為、
由合成流程1所合成出來的化合物示例，列於下面表1：
SC-92之合成方法(合成流程1之示例)
在化合物SC-92的合成中，首先將對氟苯甲腈(4-fluorobenzonitrile)與5-胺基-2-氯酚耦合，然後與三光氣(triphosgene)反應得到化合物SC-92。
在第一個步驟中，合成中間物4-(5-胺基-2-氯苯氧基)苯甲腈。將叔丁醇鉀(0.245g,2.19mmol))於冰浴條件下加入5-胺基-2-氯苯(0.25g,1.75mmol)之DMSO(1mL)溶液。將對氟苯甲腈(0.176,1.45mmol)加入溶液中，並於室溫中攪拌5分鐘然後以微波爐加熱至150℃維持20分鐘。加入冰水，以乙酸乙酯(3×100mL)萃取該懸浮液。收集有機相並以飽和食鹽水洗滌，以MgSO4乾燥並過濾。將過濾物濃縮並層析純化，以得到中間物4-(5-胺基-2-氯苯氧基)苯甲腈(4-(5-amino-2-chlorophenoxy)benzonitrile)。
4-(5-胺基-2-氯苯氧基)苯甲腈：1H NMR(400MHz,MeOD)：δ 7.68(d,J=8.8Hz,2H),7.18(d,J=8.8Hz,1H),6.99(d,J=8.8Hz,2H),6.58(dd,J=8.4Hz,2.8Hz,1H),6.49(d,J=2.8Hz,1H)。
在第二步驟中，合成產物1,3-二(4-氯-3-(4-氰基苯氧基)苯基)脲(1,3-bis(4-chloro-3-(4-cyanophenoxy)phenyl)urea；SC-92)。首先，在乾燥THF(3mL)中的4-(5-胺基-2-氯苯氧基)苯甲腈(0.148g,0.61mmol)與三乙胺(triethylamine；0.153mL,1.1mmol)於冰浴條件下緩慢加入含有三光氣(0.082 g,0.28mmol)的乾燥THF(3mL)溶液。將混合物於60℃、氮氣環境下攪拌過夜。在降溫至室溫後，將所得溶液過濾以去除鹽，並濃縮該過濾物。濃縮後過濾物以正己烷(3 x 5mL)清洗並收集沉澱物，再減壓乾燥以得到1,3-二(4-氯-3-(4-氰基苯氧基)苯基)脲。
實施例2：在合成流程I中Ar為
N為0或1。
X為N或C-R1。
R1為H或Cl。
R2為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R3為H、一鹵素或一烷基。該鹵素例如為F、Cl、或Br。該烷基例如為CH3或CH2CH3。
R4為H、一鹵素或一烷基。該鹵素例如為F或Cl。該烷基例如為CH3或CH2CH3。
R5為H、一鹵素、一烷基、一烷氧基、或一羥基。該鹵素例 如為F或Cl。該烷基例如為CH3或CH2CH3。
R6為H或一羥基。
R5與R6可共同形成一二價飽和或不飽和基團，例如。
R7為一未取代或經取代的芳香基。例如，R7為一經取代的苯 基或一經取代的。該經取代的苯基例如可為、 、、、、或。該經取代 的例如可為。
將合成流程2所合成之化合物的示例，列於下表2。
實施例3：合成流程I中Ar為
在合成流程3中，n為0。
C為C-R1。
R1為H或Cl。
R2、R3、及R6為H。
R7為一經取代的苯基、一經取代的、或 。該經取代的苯基例如為。該經取代的 例如為。
將合成流程3所合成化合物之示例，列於下表3。
SC-72之合成方法(合成流程3之示例)
在第一步驟中，將對氟苯甲腈與8-胺基-2-萘酚(8-aminonaphthalen-2-ol)耦合，在叔丁醇鉀存在的環境中產生中間物4-((8-胺基萘-2-基)氧基)苯甲腈(4-((8-aminonaphthalen-2-yl)oxy)benzonitrile，化學結構式如下所示)。
將叔丁醇鉀(0.42g,3.72mmol)加入在DMSO(1mL)中的8-胺基-2-萘酚(0.394g,2.48mmol)，並將溫度降至4℃。將對氟苯甲腈(0.3g,2.48mmol)加入反應混合物中並於室溫中攪拌5分鐘，然後以微波加熱至150℃並維持20分鐘。在該反應混合物之溫度降至室溫後，加入冰水以中止反應。以乙酸乙酯(3x100mL)萃取該溶液。收集有機相，以飽和食鹽水(brine)洗滌，以無水MgSO4乾燥並過濾，將濾液濃縮並層析純化以得到中間物4-((8-胺基萘-2-基)氧基)苯甲腈。
4-((8-胺基萘-2-基)氧基)苯甲腈：1H NMR(400MHz,CDCl3)：δ 7.84(d,J=8.8Hz,1H),7.58(d,J=8.8Hz,2H),7.46(d,J=2.4Hz,1H),7.34-7.24(m,2H),7.17(dd,J=8.8Hz,2.4Hz,1H),7.02(d,J=8.8Hz, 2H),6.81(dd,J=7.2Hz,1.2Hz,1H)。
在第二步驟中，該4-((8-胺基萘-2-基)氧基)苯甲腈及4-氯-3-三氟甲基苯胺(4-chloro-3-(trifluoromethyl)aniline)與三光氣反應以得到化合物SC-72。在乾燥THF(3mL)中的4-氯-3-三氟甲基苯胺(0.18g,0.69mmol)與三乙胺(0.38mL,2.76mmol))於冰浴條件下緩慢加入在乾燥THF(3mL)中的三光氣(0.205g,0.69mmol)。該混合物於60℃、氮氣環境下攪拌30分鐘。待溫度回到室溫後，將在乾燥THF(3mL)中的4-((8-胺基萘-2-基)氧基)苯甲腈(0.135g,0.69mmol))於冰浴條件下緩慢加入該混合物，並加熱至60℃隔夜。過濾所得溶液以去除鹽，然後濃縮以進行層析。在層析純化後，得到1-(4-氯-3-(三氟甲基)苯基)-3-(7-(4-氰基苯氧基)萘-1-基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(7-(4-cyanophenoxy)naphthalen-1-yl)-urea；SC-72)。
合成流程II之第一步驟與前述合成流程I之第一步驟相同，且合成流程I之化合物A為合成流程II之化合物A’的簡化。因此，合成流程II第 一步驟的詳細敘述在此省略。
在第二步驟中，亞硫醯氯(thionyl chloride)緩慢加入1當量之於二氯甲烷中的1,1-環丙基二甲酸(1,1-cyclopropanedicarboxylic acid)。反應混合物於40℃攪拌2小時。冷卻至室溫後，反應混合物以旋轉蒸發器乾燥並溶於乾燥的THF。2當量的OH-Ar-NH2與4當量的三乙胺加入該溶液中並於40℃攪拌8小時。將該反應混合物以乙酸乙酯萃取。以飽和食鹽水(brine)洗滌所收集的有機相，且以MgSO4乾燥並過濾。將過濾物濃縮並層析純化以得到化合物II。
在合成流程II，Ar為一經取代的芳香基，例如或
實施例4：合成流程II
合成流程II所合成化合物之示例列於下表4。
化合物D與三乙胺於冰浴條件下緩慢加入含有XCl2試劑(例如草醯氯、亞硫醯氯或三光氣)之乾燥THF溶液。該混合物於60℃、氮氣環境下攪拌30分鐘。在溫度降至室溫後，將所得溶液過濾以去除鹽，並將過濾液濃縮以進行層析。在層析純化後，得到化合物III。
在合成流程III中：
R8為一鹵烷基或一經取代的苯氧基(C6H5O-)。該鹵烷基例如 為CF3。該經取代的苯氧基例如為或。
R9為H、一鹵素或一烷基。該鹵素例如為Cl。該烷基為CH3。
X為、、、或。
實施例5：合成流程III
合成流程III所合成化合物之示例列於下表5。
SC-94之合成方法(合成流程III之示例)
2.2當量之4-(5-胺基-2-甲基苯氧基)苯甲腈(4-(5-amino-2-methylphenoxy)benzonitrile)與4當量之含有三甲胺的乾燥THF於冰浴條件下緩慢加入1當量含有三光氣之乾燥THF溶液。反應混合物於60℃攪拌8小時。將所得溶液過濾以去除鹽，將過濾液濃縮進行層析以得到1,3-二(3-(4-氰基苯氧基)-4-甲基苯基)脲(1,3-bis(3-(4-cyanophenoxy)-4-methylphenyl)urea)。
於乾燥THF中的2當量的羥胺(hydroxylamine)與1.5當量的三甲胺緩慢加入於冰浴條件下1,3-二(3-(4-氰基苯氧基)-4-甲基苯基)脲之乙醇溶液。該混合物於80℃攪拌8小時。冷卻至室溫後，所得混合物以旋轉蒸發器乾燥並以二氯甲烷萃取。收集的有機相以飽和食鹽水洗滌、以MgSO4乾 燥並過濾。在以二氯甲烷與甲醇再結晶後，沉澱物以二氯甲烷清洗以得到SC-94。
在合成流程IV中，R8為經取代的苯氧基(C6H5O-)，例如
R9為H。
X為。
實施例6：合成流程IV
合成流程IV所合成化合物之示例列於下表6。
DC-69之合成方法(合成流程IV之示例)
1當量的草醯氯於冰浴條件下溶於乾燥的THF。在THF中的1 當量的4-氯-3-三氟甲基苯胺與4當量的三甲胺緩慢地加入反應混合物中。將該混合物於60℃攪拌30分鐘。在冷卻至室溫後，於THF中1當量的4-(3-胺基苯氧基)苯甲腈(4-(3-aminophenoxy)benzonitrile)於冰浴條件下緩慢加入該混合物。將該混合物於60℃攪拌8小時。將所得溶液過濾以去除鹽並濃縮以進行層析而得到化合物SC-69。
SC示例化合物之光譜數據
1-(3-(4-氰基苯氧基)苯基)-3-(3-乙炔基苯基)脲(1-(3-(4-cyanophenoxy)phenyl)-3-(3-ethynylphenyl)urea；SC-65)
1H NMR(400MHz,MeOD-d 4 )：δ 7.70(d,J=8.8Hz,1H),7.57(s,1H),7.42-7.33(m,3H),7.25(t,J=8.0Hz,1H),7.21(d,J=8.0Hz,1H),7.12-7.09(m,3H),6.75(dd,J=8.0Hz,1H),3.45(s,1H)；13C NMR(100MHz,MeOD-d 4 )：δ 163.0,156.8,154.8,142.5,140.5,135.4,131.4,129.9,127.4,124.2,123.4,120.7,119.6,116.5,115.2,112.0,106.8,84.2,78.4；C22H15N3O2的HRMS計算值：352.1086；實測值：352.1080。
1-(3-(4-氰基苯氧基)-4-甲氧基苯基)-3-(3-乙炔基苯基)脲(1-(3-(4-cyanophenoxy)-4-methylphenyl)-3-(3-ethynylphenyl)urea；SC-66)
1H NMR(400MHz,MeOD-d 4 )：δ 7.68(d,J=9.2Hz,2H),7.56(t,J=2.0Hz,1H),7.39(dd,J=8.0,2.0Hz,1H),7.28-7.22(m,3H),7.16 (dd,J=8.4,2,.4Hz,1H),7.11(d,J=7.6Hz,1H),7.01(d,J=9.2Hz,2H),3.47(s,1H),1.89(s,3H)；C23H17N3O2(M+H)+的HRMS計算值：368.1399；實測值：368.1413。
N,N'-二(3-(4-氰基苯氧基)苯基)環丙烷-1,1-二甲醯胺(N,N'-bis(3-(4-cyanophenoxy)phenyl)cyclopropane-1,1-dicarboxamide；SC-67)
1H NMR(400MHz,CDCl3-d 1 )：δ 7.57(d,J=9.2Hz,4H),7.47(s,1H),7.32(t,J=8.0Hz,1H),7.28(d,J=8.0Hz,1H),6.99(d,J=9.2Hz,4H),6.78(dd,J=7.6Hz,2.2Hz,2H),1.76-1.75(m,4H)；C31H22N4O4(M+Na)+的HRMS計算值：537.1539；實測值：537.1562。
1-(3-(4-氰基苯氧基)-4-甲基苯基)胺基甲醯基)環丙烷-1-羧酸(1-(3-(4-cyanophenoxy)-4-methylphenyl)carbamoyl)cyclopropane-1-carboxylic acid；SC-68)
1H NMR(400MHz,CDCl3-d 1 )：δ 7.54(d,J=8.8Hz,4H),7.37(s,2H),7.21(d,J=2.0Hz,4H),6.88(d,J=8.8Hz,4H),2.09(s,6H),1.77(d,J=16Hz,4H)；13C NMR(100MHz,CDCl3-d 1 )：δ 177.3,166.7,161.5,152.3,137.1,134.1,131.8,126.3,118.8,117.4,116.7,113.3,105.2,26.1,21.8,15.5；C19H16N2O4的HRMS計算值：336.1110；實測值：336.1115。
N 1 -(4-氯-3-(三氟甲基)苯基)-N 2 -(3-(4-氰基苯氧基)苯基)草醯胺(N 1 -(4-chloro-3-(trifluoromethyl)phenyl)-N 2 -(3-(4-cyanophenoxy)phenyl)oxalamide；SC-69)
1H NMR(400MHz,DMSO-d 6 )：δ 8.47(d,J=2.0Hz,1H),8.15(dd,J=8.8,2.0Hz,1H),7.87(d,J=8.8Hz,2H),7.75-7.70(m,3H),7.46(t,J=8.0Hz,1H),7.17(d,J=8.8Hz,2H),6.95(dd,J=8.0,2.0Hz,1H)；13C NMR(100MHz,DMSO-d 6 )：δ 160.5,158.7,158.1,154.9,139.2,137.1,134.6,132.1,130.5,126.6(m),125.4,125.2,122.6(m),119.3(m),118.9,118.6,116.6,115.8,111.4,105.5；C22H13ClF3N3O3的HRMS計算值：459.0598；實測值：459.0607。
N 1 -(3-((4-氰基環己烷-2,4-二烯-1-基)氧基)環己-2,4-二烯-1-基)-N 2 -(3-(4-氰基苯氧基)苯基)草醯胺(N 1 -(3-((4-cyanocyclohexa-2,4-dien-1-yl)oxy)cyclohexa-2,4-dien-1-yl)-N 2 -(3-(4-cyanophenoxy)phenyl)oxalamide；SC-70)
1H NMR(400MHz,DMSO-d 6 )：δ 10.99(s,1H),7.86(d,J=8.8Hz,2H),7.73(d,J=8.4Hz,1H),7.69(s,1H),7.45(t,J=8.4Hz,1H),7.16(d,J=8.8Hz,2H),6.93(d,J=8.4Hz,1H)；13C NMR(100MHz,DMSO-d 6 )：δ 160.4,158.3,154.8,139.2,134.5,130.4,118.5,116.5,115.7,111.3,105.3。
N 1 -(3-((4-氰基環己烷-2,4-二烯-1-基)氧基)-4-甲基環-2,4-二烯-1-基)-N 2 -(3-(4-氰基苯氧基)-4-甲基苯基)草醯胺(N 1 -(3-((4-cyanocyclohexa-2,4-dien-1-yl)oxy)-4-methylcyclohexa-2,4-dien- 1-yl)-N 2 -(3-(4-cyanophenoxy)-4-methylphenyl)oxalamide；SC-71)
1H NMR(400MHz,DMSO-d 6 )：δ 10.88(s,1H),7.83(d,J=8.8Hz,2H),7.65(d,J=8.4Hz,1H),7.61(s,1H),7.35(d,J=8.4Hz,1H),7.05(d,J=8.8Hz,2H),2.09(s,3H)；13C NMR(100MHz,DMSO-d 6 )：160.6,158.1,151.9,136.9,134.5,131.6,125.4,118.5,117.3,117.0,112.0,104.7,15.0；C29H23N5O3(M+H)+的HRMS計算值：507.2032；實測值507.2054。
1-(4-氯-3-(三氟甲基)苯基)-3-(7-(4-氰基苯氧基)萘-1-基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(7-(4-cyanophenoxy)naphthalen-1-yl)urea；SC-72)
1H NMR(400MHz,DMSO-d 6 )：δ 8.09-8.07(m,2H),7.97(d,J=7.6Hz,1H),7.83-7.81(m,3H),7.75(d,J=8.4Hz,1H),7.64-7.58(m,2H),7.50(t,J=7.6Hz,1H),7.37(d,J=9.2Hz,1H),7.15(d,J=8.4Hz,2H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.3,152.7,151.8,146.6,139.2,134.6,133.5,131.9,131.4,131.3,127.3,126.6(m),125.5,123.6,122.8,122.5(m),120.3,119.3,118.5,117.6,116.6(m),111.7,105.0；C25H15ClF3N3O2(M-H)-的HRMS計算值：480.0727；實測值：480.0705。
1,3-二(7-(4-氰基苯氧基)萘-1-基)脲(1,3-bis(7-(4-cyanophenoxy)naphthalen-1-yl)urea；SC-73)
1H NMR(400MHz,DMSO-d 6 )：δ 8.99(s,2H),8.08-8.05(m,4H),7.93(d,J=2.4Hz,2H),7.83(d,J=8.8Hz,4H),7.72(d,J=8.4Hz,2H),7.51(t,J=8.0Hz,2H),7.37(dd,J=9.2,2.4Hz,2H),7.14(d,J=8.8Hz,4H)；C35H22N4O3(M+Na)+的HRMS計算值：569.1590；實測值：569.1589。
1-((7-(4-氰基苯氧基)萘-1-基)胺基甲酰基)環丙烷羧酸(1-((7-(4-cyanophenoxy)naphthalen-1-yl)carbamoyl)cyclopropane carboxylic acid；SC-75)
1H NMR(400MHz,CDCl3-d 1 )：δ 10.93(s,1H),8.05(d,J=7.6Hz,1H),7.89(d,J=8.8Hz,1H),7.68(d,J=8.4Hz,1H),7.63-7.59(m,3H),7.45(t,J=7.6Hz,1H),7.22(dd,J=8.8,2.4Hz,1H),7.06(d,J=8.8Hz,2H),1.89(s,2H),1.76(s,2H)；C22H16N2O4的HRMS計算值：372.1110；實測值：372.1103。
1,3-二(3-(4-氰基苯氧基)苯基)硫脲(1,3-bis(3-(4-cyanophenoxy)phenyl)thiourea；SC-76)
1H NMR(400MHz,MeOD-d 4 )：δ 7.76(d,J=8.8Hz,2H), 7.59(t,J=8.0Hz,1H),7.25-7.19(m,2H),7.18(d,J=8.8Hz,2H),7.12(t,J=2.4Hz,1H)；13C NMR(100MHz,MeOD-d 4 )：δ 161.8,158.0,135.7,134.0,133.1,121.2,120.2,120.1,115.7,108.3。
1,3-二(4-氯-3-(三氟甲基)苯基)脲(1,3-bis(4-chloro-3-(trifluoromethyl)phenyl)urea；SC-78)
1H NMR(400MHz,MeOD-d 4 )：δ 7.97(s,2H),7.64(d,J=8.8Hz,2H),7.49(d,J=8.8Hz,2H)；13C NMR(100MHz,MeOD-d 4 )：δ 154.2,139.8,132.9,129.3(m),125.7,124.4(m),124.3,118.8；C15H8Cl2F6N2O(M-H)-的HRMS計算值：414.9840；實測值：414.9847。
1-(4-氯-3-(三氟甲基)苯基)-3-(3-(3-氯-4-氰基苯氧基)苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(3-chloro-4-cyanophenoxy)phenyl)urea；SC-79)
1H NMR(400MHz,MeOD-d 4 )：δ 7.95(d,J=2.8Hz,1H),7.76(t,J=8.8Hz,1H),7.64(dd,J=8.8,2.8Hz,1H),7.49(d,J=8.8Hz,1H),7.42(t,J=2.0Hz,1H),7.38(t,J=8.0Hz,1H),7.26(dd,J=8.0,2.0Hz,1H),7.18(d,J=2.4Hz,1H),7.05(dd,J=8.8,2.4Hz,1H),6.79(dd,J=8.0,2.4Hz,1H)；13C NMR(100MHz,MeOD-d 4 )：δ 163.8,156.2,154.5,142.5,140.0,139.1,136.9,133.0,131.6,129.4(q),125.6,124.3,122.9,119.7,118.8(q),17.5,117.2,116.8,115.6,112.4,107.6。
1-(4-氯-3-(三氟甲基)苯基)-3-(3-(4-氰基-2-氟苯氧基)苯基)脲 (1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(4-cyano-2-fluorophenoxy)phenyl)urea；SC-80)
1H NMR(400MHz,MeOD-d 4 )：δ 7.95(d,J=2.8Hz,1H),7.71(dd,J=10.4,2.0Hz,1H),7.63(dd,J=8.4,2.0Hz,1H),7.54(d,J=8.0Hz,1H),7.49(d,J=9.2Hz,1H),7.39(t,J=2.0Hz,1H),7.35(t,J=8.4Hz,1H),7.21(d,J=8.4Hz,1H),7.14(t,J=8.0Hz,1H),6.75(dd,J=8.0,2.8Hz,1H)；C21H12ClF4N3O2(M-H)-的HRMS計算值：448.0476；實測值：448.0476。
1,3-二(3-(3-氯-4-氰基苯氧基)-4-甲基苯基)脲(1,3-bis(3-(3-chloro-4-cyanophenoxy)-4-methylphenyl)urea；SC-82)
1H NMR(400MHz,DMSO-d 6 )：δ 8.82(s,2H),7.93(d,J=8.8Hz,2H),7.34(d,J=2.4Hz,2H),7.27(d,J=8.8Hz,2H),7.23(d,J=2.4Hz,2H),7.16(dd,J=2.4Hz,2H),6.94(dd,J=8.8,2.4Hz,2H),2.04(s,6H)；13C NMR(100MHz,DMSO-d 6 )：δ 171.4,161.9,161.0,148.8,146.7,145.9,141.5,132.2,127.0,125.5,125.0,120.0,114.9,24.4；C29H20Cl2N4O3的HRMS計算值：542.0912；實測值：542.0910。
1,3-二(3-(3-溴-4-氰基苯氧基)-4-甲基苯基)脲(1,3-bis(3-(3-bromo-4-cyanophenoxy)-4-methylphenyl)urea；SC-83)
1H NMR(400MHz,DMSO-d 6 )：δ 8.90(s,1H),7.96(d,J=8.8 Hz,1H),7.45-7.39(m,2H),7.33(d,J=8.4Hz,1H),7.23(dd,J=8.4,2.0Hz,1H),7.04(dd,J=8.8Hz,1H),2.05(s,3H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.0,151.8,150.9,138.7,136.0,131.4,125.5,122.0,119.8,116.6,115.6,115.3,110.0,107.2,14.3；C29H20Br2N4O3(M-H)-的HRMS計算值：628.9824；實測值：628.9842。
1,3-二(3-(4-氰基-3-氟苯基)-4-甲基苯基)脲(1,3-bis(3-(4-cyano-3-fluorophenoxy)-4-methylphenyl)urea；SC-84)
1H NMR(400MHz,DMSO-d 6 )：δ 8.85(s,2H),8.01(dd,J=8.8,6.4Hz,2H),7.34(d,J=2.0Hz,2H),7.28(d,J=8.4Hz,2H),7.18-7.12(m,4H),6.59(dd,J=10.4,2.4Hz,2H),2.06(s,6H)；C29H20F2N4O3(M-H)-的HRMS計算值：509.1425；實測值：509.1424。
1,3-二(3-(4-氰基-2-氟苯氧基)-4-甲基苯基)脲(1,3-bis(3-(4-cyano-2-fluorophenoxy)-4-methylphenyl)urea；SC-85)
1H NMR(400MHz,DMSO-d 6 )：δ 8.79(s,1H),8.03(dd,J=11.2,2.0Hz,1H),7.62(d,J=8.4Hz,1H),7.25-7.23(m,2H),7.12(dd,J=8.4,2.0Hz,1H),6.89(t,J=8.4Hz,1H),2.07(s,3H)。
1,3-二(3-((6-氰基吡啶-3-基)氧基)-4-甲基苯基)脲(1,3-bis(3-((6-cyanopyridin-3-yl)oxy)-4-methylphenyl)urea；SC-86)
1H NMR(400MHz,DMSO-d 6 )：δ 8.88(s,1H),8.47(d,J=2.1Hz,1H),7.99(d,J=8.4Hz,1H),7.33(dd,J=8.4,2.1Hz,2H),7.27(d,J=8.4Hz,1H),7.15(dd,J=8.0,2.0Hz,1H),2.05(s,3H)；13C NMR(100MHz,DMSO-d 6 )：δ 156.5,152.3,151.4,141.0,139.2,131.9,130.6,125.5,123.2,122.4,117.4,115.8,110.1,14.8。
1-(4-氯-3-(三氟甲基)苯基)-3-(3-((6-氰基吡啶-3-基)氧基)-4-甲基苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-((6-cyano-pyridin-3-yl)oxy)-4-methylphenyl)urea；SC-87)
1H NMR(400MHz,DMSO-d 6 )：δ 9.15(s,1H),8.94(s,1H),8.49(m,1H),8.05(s,H),8.00(d,J=8.0Hz,1H),7.59-7.58(m,2H),7.37-7.33(m,2H),7.29(d,J=8.4Hz,1H),7.22(dd,J=8.4,2.0Hz,1H),2.06(s,1H)；13C NMR(100MHz,DMSO-d 6 )：δ 156.1,151.9,151.1,140.7,138.8,138.6(m),131.6,130.3,126.7,126.4,125.3,122.9,122.8,122.7,122.5,122.4(m),117.0,116.5,115.8,110.2,14.5；C21H14ClF3N4O2(M-H)-的HRMS計算值：445.0679；實測值：445.0679。
1-(4-氯-3-(三氟甲基)苯基)-3-(3-(4-氰基-3-氟苯基)-4-甲基苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(4-cyano-3-fluoro-phenoxy)-4-methylphenyl)urea；SC-88)
1H NMR(400MHz,MeOD-d 4 )：δ 7.94(d,J=2.8Hz,1H), 7.81(dd,J=8.8,6.0Hz,1H),7.63(dd,J=8.8,2.8Hz,1H),7.48(d,J=8.8Hz,1H),7.35(d,J=2.0Hz,1H),7.30(d,J=8.4Hz,1H),7.22(dd,J=8.4,2.0Hz,1H),6.97-6.94(m,1H),6.51(dd,J=10.4,2.4Hz,1H),2.15(s,3H)；C22H14ClF4N3O2(M-H)-的HRMS計算值：462.0632；實測值：462.0645。
1-(3-(3-溴-4-氰基苯氧基)-4-甲基苯基)-3-(4-氯-3-(三氟甲基)苯基)脲(1-(3-(3-bromo-4-cyanophenoxy)-4-methylphenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea；SC-89)
1H NMR(400MHz,DMSO-d 6 )：δ 9.15(s,1H),8.94(s,1H),8.06(d,J=2.0Hz,1H),7.90(d,J=8.8Hz,1H),7.60-7.58(m,2H),7.35-7.34(m,2H),7.28(d,J=8.8Hz,1H),7.22(dd,J=8.4,2.0Hz,1H),6.98(dd,J=8.8,2.4Hz,1H),2.04(s,1H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.4,152.1,151.3,139.0,138.8,136.5,131.8,126.5(m),125.9,124.0,123.0,122.9,122.7,122.3,120.3,117.0,116.7(m),116.1,115.6,110.8,107.6,14.7；C22H14BrClF3N3O2(M-H)-的HRMS計算值：521.9832；實測值：521.9821。
1,3-二(4-(4-氰基苯氧基)-2-甲基苯基)脲(1,3-bis(4-(4-cyanophenoxy)-2-methylphenyl)urea；SC-90)
1H NMR(400MHz,DMSO-d 6 )：δ 8.32(s,2H),7.86(d,J=8.0Hz,2H),7.82(d,J=8.0Hz,4H),7.07(d,J=8.0Hz,4H),7.03(d,J=4.0Hz,2H),6.95(dd,J=8.0,4.0Hz,2H),2.29(s,6H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.5,152.8,148.9,134.5,134.3,130.4,123.1,121.8,118.5, 117.9,117.2,104.3,17.8；C29H22N4O3(M-H)-的HRMS計算值：473.1614；實測值：473.1608。
1,3-二(2-氯-5-(4-氰基苯氧基)苯基)脲(1,3-bis(2-chloro-5-(4-cyanophenoxy)phenyl)urea；SC-91)
1H NMR(400MHz,DMSO-d 6 )：δ 9.27(s,2H),7.88(d,J=3.2Hz,2H),7.82(d,J=8.8Hz,4H),7.53(d,J=8.8Hz,2H),7.12(d,J=8.8Hz,4H),6.83(dd,J=8.8,3.2Hz,2H)；13C NMR(100MHz,DMSO-d 6 )：δ 160.6,153.3,151.9,137.0,134.6,130.6,118.5,118.2,118.1,115.3,113.4,105.4；C27H16Cl2N4O3(M-H)-的HRMS計算值：513.0521；實測值：513.0516。
1,3-二(4-氯-3-(4-氰基苯氧基)苯基)脲(1,3-bis(4-chloro-3-(4-cyanophenoxy)phenyl)urea；SC-92)
1H NMR(400MHz,DMSO-d 6 )：δ 9.08(s,2H),7.84(d,J=8.8Hz,4H),7.52-7.48(m,4H),7.28(dd,J=8.8,2.4Hz,2H),7.06(d,J=8.8Hz,4H)；13C NMR(100MHz,DMSO-d 6 )：δ 160.1,151.9,149.3,140.0,134.5,130.7,118.4,117.5,117.0,116.6,111.9,105.2；C27H16Cl2N4O3(M-H)-的HRMS計算值：513.0521；實測值：513.0524。
1,3-二(5-(4-氰基苯氧基)-2-甲基苯基)脲(1,3-bis(5-(4-cyanophenoxy)-2-methylphenyl)urea；SC-93)
1H NMR(400MHz,DMSO-d 6 )：δ 8.52(s,2H),7.80(d,J=8.8Hz,4H),7.71(d,J=2.8Hz,2H),7.27(d,J=8.4Hz,2H),7.06(d,J=8.8Hz,4H),6.73(dd,J=8.4,2.8Hz,2H),2.29(s,6H)；13C NMR(100MHz,DMSO-d 6 )：δ 170.8,161.9,161.6,148.3,143.9,140.9,133.2,128.1,126.9,123.5,121.9,114.0,26.9；C29H22N4O3(M-H)-的HRMS計算值：473.1614；實測值：473.1598。
(1Z,1'Z)-4,4'-(((羰基二(脲二基))二(2-甲基-5,1-亞苯基))二(氧基))二(N'-羥基苯甲醯胺)((1Z,1'Z)-4,4'-(((carbonylbis-(azanediyl))bis(2-methyl-5,1-phenylene))bis(oxy))bis(N'-hydroxy-benzimidamide)；SC-94)
1H NMR(400MHz,MeOD-d 4 )：δ 7.84(d,J=8.8Hz,2H),7.59(d,J=8.8Hz,2H),7.21-7.17(m,4H),7.14-7.06(m,4H),6.93-6.89(m,2H)；C29H28N6O5(M+H)+的HRMS計算值：541.2199；實測值：541.2178。
1-(4-氯-3-(三氟甲基)苯基)-3-(4-(4-氰基苯氧基)-2-氟苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(4-cyanophenoxy)-2-fluorophenyl)urea；SC-96)
1H NMR(400MHz,DMSO-d 6 )：δ 9.47(s,1H),8.68(s,1H),8.11-8.06(m,2H),7.84(d,J=8.8Hz,2H),7.63-7.58(m,2H),7.23(dd,J=11.6,2.8Hz,1H),7.12(d,J=8.8Hz,2H),6.98(dd,J=8.8,1.6Hz,1H)； C21H12ClF4N3O2(M-H)-的HRMS計算值：448.0476；實測值：448.0477。
1,3-二(5-(4-氰基苯氧基)-2-氟苯基)脲(1,3-bis(5-(4-cyanophenoxy)-2-fluorophenyl)urea；SC-97)
1H NMR(400MHz,DMSO-d 6 )：δ 9.32(s,2H),7.94(m,2H),7.81(d,J=8.8Hz,4H),7.35(t,J=9.2Hz,2H),7.07(d,J=8.8Hz,4H),6.81(m,2H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.1,151.5,149.9,147.4,134.4,128.5,118.4,117.4,116.1,113.9,111.8,104.8；C27H16F2N4O3(M-H)-的HRMS計算值：481.1112；實測值：481.1110。
1,3-二(3-(4-氰基-3-甲基苯氧基)-4-甲基苯基)脲(1,3-bis(3-(4-cyano-3-methylphcnoxy)-4-methylphenyl)urea；SC-98)
1H NMR(400MHz,DMSO-d 6 )：δ 8.76(s,1H),7.72(d,J=8.4Hz,2H),7.26(d,J=2.0Hz,2H),7.23(d,J=8.0Hz,2H),7.12(dd,J=8.4,2.4Hz,2H),6.93(d,J=2.0Hz,2H),6.77(dd,J=8.4,2.4Hz,2H),2.41(s,6H),2.02(s,6H)；13C NMR(100MHz,DMSO-d 6 )：δ 160.7,152.1,151.8,144.1,138.9,134.5,131.5,122.4,117.7,117.5,115.2,114.0,110.3,105.0,19.8,14.8；C31H26N4O3(M-H)-的HRMS計算值：501.1927；實測值：501.1924。
1-(3-(4-氰基苯氧基)-4-甲氧基苯基)-3-(3-((6-氰基吡啶-3-基)氧基)-4-甲基苯基)脲(1-(3-(4-cyanophenoxy)-4-methylphenyl)-3-(3-((6-cyanopyridin-3-yl)oxy)-4-methylphenyl)urea；SC-99)
1H NMR(400MHz,CDCl3-d 1 )：δ 8.29(d,J=2.8Hz,1H),7.52(d,J=8.8Hz,1H),7.48(d,J=9.2Hz,2H),7.36(s,1H),7.25(s,1H),7.15(d,J=2.0Hz,1H),7.11-7.06(m,4H),6.98(t,J=12.0Hz,2H),6.84(d,J=9.2Hz,2H),2.05(s,3H),2.04(s,3H)。
1-(3-(3-氯-4-氰基苯氧基)-4-甲基苯基)-3-(3-(4-氰基苯氧基)-4-甲基苯基)脲(1-(3-(3-chloro-4-cyanophenoxy)-4-methylphenyl)-3-(3-(4-cyanophenoxy)-4-methylphenyl)urea；SC-100)
1H NMR(400MHz,CDCl3-d 1 )：δ 7.56-7.53(m,3H),7.20-7.16(m,3H),7.16(s,1H),7.11(s,1H),7.07-7.03(m,2H),6.92-6.87(m,3H),6.81(d,J=8.8Hz,1H),6.62(d,J=10.4Hz,1H),6.56(d,J=9.6Hz,1H),2.09(s,6H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.7,152.2,151.9,151.4,139.2,139.1,137.1,136.3,134.5,131.8,131.7,122.6,118.6,117.4,116.8,115.9,115.4,115.3,110.6,105.6,104.4,14.9,14.8；C29H21ClN4O3(M-H)-的HRMS計算值：507.1224；實測值：507.1218。
1-(3-(4-氰基-3-甲基苯氧基)-4-甲基苯基)-3-(3-((6-氰基吡啶-3-基)氧基)-4-甲基苯基)脲(1-(3-(4-cyano-3-methylphenoxy)-4-methylphenyl)-3-(3-((6-cyanopyridin-3-yl)oxy)-4-methylphenyl)urea；SC-102)
1H NMR(400MHz,MeOD-d 4 )：δ 8.37(d,J=2.8Hz,1H),7.78(d,J=8.4Hz,1H),7.57(d,J=8.8Hz,1H),7.31(dd,J=8.4,2.8Hz,2H),7.25(d,J=8.4Hz,1H)；13C NMR(100MHz,DMSO-d 6 )：δ 160.9,156.5,152.2,152.1,152.0,151.4,144.3,141.0,139.2,139.0,134.7,131.9,131.7,130.6,125.5,123.2,122.6,122.3,117.9,117.6,117.3,115.8,115.7,114.1,110.5,110.2,110.1,105.1,19.9,14.9,14.8；C29H23N5O3(M-H)-的HRMS計算值：488.1723；實測值：488.1718。
1-(3-(3-氯-4-氰基苯氧基)-4-甲基苯基)-3-(3-((6-氰基吡啶-3-基)氧基)51-4-甲基苯基)脲(1-(3-(3-chloro-4-cyanophenoxy)-4-methylphenyl)-3-(3-((6-cyanopyridin-3-yl)oxy)51-4-methylphenyl)urea；SC-103)
1H NMR(400MHz,CDCl3-d 1 )：δ 8.28(d,J=2.8Hz,1H),7.61(d,J=9.6Hz,2H),7.51(d,J=8.4Hz,1H),7.46(d,J=8.8Hz,1H),7.17(dd,J=18.2,2.0Hz,2H),7.08(d,J=8.8Hz,3H),6.93-6.89(m,2H),6.86(d,J=2.0Hz,1H),6.75(dd,J=8.8,2.4Hz,1H),2.04(s,3H),2.02(s,3H)；C28H20ClN5O3(M-H)-的HRMS計算值：508.1176；實測值：508.1176。
1,3-二(3-((6-氰基-5-氟吡啶-3-基)氧基)-4-甲基苯基)脲(1,3-bis(3-((6-cyano-5-fluoropyridin-3-yl)oxy)-4-methylphenyl)urea；SC-104)
1H NMR(400MHz,MeOD-d 4 )：δ 8.13(t,J=2.4Hz,2H),7.36(d,J=8.4Hz,2H),7.24-7.19(m,4H),7.14(dd,J=8.4,2.4Hz,2H),2.31(s,6H)；C27H18F2N6O3(M-H)-的HRMS計算值：511.1330；實測值：511.1333。
1-(4-氯-3-(三氟甲基)苯基)-3-(5-(4-氰基苯氧基)-2-氟苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(5-(4-cyanophenoxy)-2-fluorophenyl)urea；SC-105)
1H NMR(400MHz,DMSO-d 6 )：δ 8.04(d,J=2.4Hz,1H),7.94(dd,J=6.8,3.2Hz,1H),7.84(d,J=8.8Hz,2H),7.62-7.57(m,2H),7.38-7.33(m,1H),7.05(d,J=8.8Hz,2H),6.84-6.80(m,1H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.1,151.7,150.0,147.6,138.5,134.4,131.9,128.4,126.7(m),122.9,122.6(m),118.5,117.4,116.5(m),116.2,116.0,114.1,112.1,104.9；C21H12ClF4N3O2(M-H)-的HRMS計算值：448.0476；實測值：448.0454。
1,3-二(4-(4-氰基苯氧基)-2-氟苯基)脲(1,3-bis(4-(4-cyanophenoxy)-2-fluorophenyl)urea；SC-106)
1H NMR(400MHz,DMSO-d 6 )：δ 9.05(s,2H),8.19(t,J=9.2Hz,2H),7.83(d,J=8.8Hz,4H),7.22(dd,J=12.0,2.4Hz,2H),7.11(d,J=8.8Hz,4H),6.98(d,J=9.2Hz,2H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.5,153.3,151.8,150.9,148.7,134.5,124.5,121.5,118.5,117.6,116.7,108.4,108.2,105.0；C27H16F2N4O3(M-H)-的HRMS計算值：481.1112；實測值：481.1106。
1-(3-(4-氰基苯氧基)-4-甲氧基苯基)-3-(7-(4-氰基苯氧基)萘-1-基)脲(1-(3-(4-cyanophenoxy)-4-methylphenyl)-3-(7-(4-cyanophenoxy)-naphthalen-1-yl)urea；SC-107)
1H NMR(400MHz,DMSO-d 6 )：δ 9.01(s,1H),8.67(s,1H),8.06(d,J=8.8Hz,1H),7.98(d,J=6.8Hz,1H),7.84-7.79(m,5H),7.70(d,J=7.6Hz,1H),7.47(t,J=8.0Hz,1H),7.36(dd,J=9.6,2.4Hz,2H),7.27(d,J=8.0Hz,1H),7.16-7.12(m,3H),7.02(d,J=9.6Hz,2H),2.05(s,3H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.4,161.1,152.7,152.0,151.7,139.3,134.7,134.6,133.8,131.8,131.4,131.3,126.9,125.6,123.1,122.5,120.3,118.7,118.6,118.4,117.6,117.0,115.2,111.6,110.3,105.0,104.5,14.9；C32H22N4O3(M-H)-的HRMS計算值：509.1614；實測值：509.1592。
1-(4-氯-3-(三氟甲基)苯基)-3-(4-(3-氯-4-氰基苯氧基)-2-氟苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(3-chloro-4-cyanophenoxy)-2-fluorophenyl)urea；SC-108)
1H NMR(400MHz,DMSO-d 6 )：δ 9.48(s,1H),8.69(s,1H),8.14-8.09(m,2H),7.94(d,J=8.8Hz,1H),7.66-7.59(m,2H),7.32(d,J=2.4Hz,1H),7.26(dd,J=11.6,2.8Hz,1H),7.07(dd,J=8.8,2.4Hz,1H),7.01(d,J=8.8Hz,1H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.6,153.7,151.9,151.3, 148.5,138.7,136.9,136.0,126.7(m),124.5,122.7,122.5(m),122.3,121.2,118.1,116.3,1162,115.7,108.5,108.3,105.7；C21H11Cl2F4N3O2的HRMS計算值：483.0164；實測值：483.0169。
1-(4-氯-3-(三氟甲基)苯基)-3-(7-(3-氯-4-氰基苯氧基)萘-1-基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(7-(3-chloro-4-cyanophenoxy)naphthalen-1-yl)urea；SC-109)
H NMR(400MHz,DMSO-d 6 )：δ 9.36(s,1H),8.82(s,1H),8.10-8.08(m,2H),7.98-7.93(m,2H),7.86(d,J=2.4Hz,1H),7.76(d,J=8.0Hz,1H),7.63-7.59(m,2H),7.51(t,J=8.0Hz,1H),7.41(dd,J=8.8,2.4Hz,1H),7.38(d,J=2.4Hz,1H),7.10(dd,J=8.8,2.4Hz,1H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.6,152.2,150.9,138.8,136.7,135.8,133.2,131.5,131.2,131.0,127.0,126.3(m),125.3,123.3,122.5,122.3(m),121.8,119.8,119.1,117.8,116.2(m),115.9,115.4,111.6,105.3；C25H14Cl2F3N3O2的HRMS計算值：515.0415；實測值：515.0419。
1-(5-(4-氰基苯氧基)-2-氟苯基)-3-(3-((6-氰基吡啶-3-基)氧基)-4-甲基苯基)脲(1-(5-(4-cyanophenoxy)-2-fluorophenyl)-3-(3-((6-cyanopyridin-3-yl)oxy)-4-methylphenyl)urea；SC-110)
1H NMR(400MHz,MeOD-d 4 )：δ 9.27(s,1H),8.97(s,1H),8.47(d,J=2.8Hz,1H),7.98(d,J=8.4Hz,1H),7.92(dd,J=7.2,2.8Hz,1H),7.81(d,J=8.8Hz,2H),7.34-7.27(m,4H),7.14(dd,J=8.4,2.0Hz,1H),7.07(d,J=8.8Hz,2H),6.79-6.76(m,1H),2.05(s,3H)；13C NMR(100MHz,DMSO-d 6 )：δ 161.3,156.5,151.8,151.5,150.2,147.6,141.1,138.8,134.6,132.1,130.6,129.0,125.6,123.2,122.9,118.6,117.6,117.4,116.8,116.3,115.8,113.8,111.9,110.2,105.0,14.9；C27H18FN5O3(M-H)-的HRMS計算值：478.1315；實測值：478.1297。
1-(4-氯-3-(三氟甲基)苯基)-3-(3-(4-氰基苯氧基)-4-氟苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(4-cyanophenoxy)-4-fluorophenyl)urea；SC-111)
1H NMR(400MHz,MeOD-d 4 )：δ 7.95(d,J=2.4Hz,1H),7.72(d,J=8.8Hz,2H),7.63(dd,J=8.8,2.4Hz,1H),7.51-7.48(m,2H),7.28-7.21(m,2H),7.09(d,J=8.8Hz,2H)；13C NMR(100MHz,MeOD-d 4 )：δ 162.6,154.5,152.6,150.2,142.5,140.0,137.6,135.4,132.9,129.1(m),125.5,124.2,119.5,118.7(m),118.4(m),118.1,117.9,115.3,107.1；C21H12ClF4N3O2的HRMS計算值：449.0554；實測值：449.0558。
1,3-二(3-(4-氰基苯氧基)-4-氟苯基)脲(1,3-bis(3-(4-cyanophenoxy)-4-fluorophenyl)urea；SC-112)
1H NMR(400MHz,DMSO-d 6 )：δ 8.97(s,2H),7.84(d,J=8.4 Hz,4H),7.49(d,J=7.2Hz,2H),7.35(t,J=9.2Hz,2H),7.24(d,J=8.8Hz,2H),7.12(d,J=8.4Hz,4H)；13C NMR(100MHz,DMSO-d 6 )：δ 160.2,152.1,149.5,147.1,140.2,140.1,136.4,134.3,118.2,117.1,116.9,116.3,116.0,115.9,112.3,105.1；C27H16F2N4O3的HRMS計算值：482.1190；實測值：482.1183。
1,3-二(3-((4-氰基萘-1-基)氧基)-4-甲基苯基)脲(1,3-bis(3-((4-cyanonaphthalen-1-yl)oxy)-4-methylphenyl)urea；SC-113)
1H NMR(400MHz,DMSO-d 6 )：δ 8.83(s,2H),8.46(d,J=8.0Hz,2H),8.12(d,J=8.4Hz,2H),8.02(d,J=8.0Hz,2H),7.88(t,J=8.4Hz,2H),7.79(t,J=8.4Hz,2H),7.37(d,J=2.0Hz,2H),7.29(d,J=8.4Hz,2H),7.18(dd,J=8.4,2.0Hz,2H),6.62(d,J=8.0Hz,2H),2.04(s,6H)；13C NMR(100MHz,DMSO-d 6 )：δ 157.1,152.0,151.8,138.9,134.3,132.9,1315,129.6,127.4,124.0,122.3,117.3,115.4,110.4,107.8,101.7；14.5。
1-(4-氯-3-(三氟甲基)苯基)-3-(3-((4-氰基萘-1-基)氧基)-4-甲基苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-((4-cyanonaphthalen-1-yl)oxy)-4-methylphenyl)urea；SC-114)
1H NMR(400MHz,MeOD-d 4 )：δ 9.15(s,1H),8.95(s,1H),8.48(d,J=8.4Hz,1H),8.13(d,J=8.4Hz,1H),8.06-8.04(m,2H),7.89(t,J=8.0Hz,1H),7.79(t,J=8.0Hz,1H),7.60-7.55(m,2H),7.41(d,J=2.0Hz, 1H),7.33(d,J=8.4Hz,1H),7.25(dd,J=8.0,2.0Hz,1H),6.65(d,J=8.0Hz,1H),2.06(s,1H)；C26H17ClF3N3O2的HRMS計算值：495.0961；實測值：495.0959。
1-(3,5-二(三氟甲基)苯基)-3-(3-(4-氰基苯氧基)-4-甲基苯基)脲(1-(3,5-bis(trifluoromethyl)phenyl)-3-(3-(4-cyanophenoxy)-4-methylphenyl)urea；SC-131)
1H NMR(300MHz,DMSO-d 6 )：δ 9.38(s,1H),9.09(s,1H),8.10(s,2H),7.82(d,J=9.0Hz,2H),7.62(s,1H),7.35(d,J=2.1Hz,1H),7.30(d,J=8.7Hz,1H),7.24(dd,J=8.7,2.1Hz,1H)7.02(d,J=9.0Hz,2H),2.05(s,3H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.1,152.3,151.9,141.7,138.7,134.7,131.9,130.7(q),128.7,125.1,121.5,118.8,118.1(d),117.9,116.9,114.4(q),113.8(q),15.0。
1-(3-(4-氰基苯氧基)-4-甲基苯基)-3-(4-氟-3-(三氟甲基)苯基)脲(1-(3-(4-cyanophenoxy)-4-methylphenyl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea；SC-132)
1H NMR(300MHz,DMSO-d 6 )：δ 9.03(s,1H),8.92(s,1H),7.95(dd,J=6.6,2.7Hz,1H),7.83(d,J=9.0Hz,2H),7.64~7.58(m,1H),7.40(t,J=9.6Hz,1H),7.33(d,J=2.1Hz,1H),7.28(d,J=8.1Hz,1H),7.19(dd,J=8.1,2.1Hz,1H),7.02(d,J=9.0Hz,2H),2.05(s,3H)；13C NMR(75MHz, DMSO-d 6 )：δ 161.1,155.3(d),152.5,152.0,139.0,136.4(d),134.7,131.8,124.4(d),123.0,120.8,118.8,117.5(d),116.9,116.6(d),116.1(q),116.0,110.9,104.6,15.0。
1-(4-氯-3-(三氟甲基)苯基)-3-(3-(4-氰基苯氧基)-4-甲基苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(3-(4-cyanophenoxy)-4-methylphenyl)urea；SC-133)
1H NMR(300MHz,DMSO-d 6 )：δ 9.16(s,1H),8.96(s,1H),8.06(s,1H),7.83(d,J=9.0Hz,2H),7.61(s,1H),7.60(s,1H),7.33(d,J=2.1Hz,1H),7.29(d,J=8.4Hz,1H),7.20(d,J=8.1,2.1Hz,1H),7.02(d,J=9.0Hz,2H),2.05(s,3H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.1,152.3,152.0,139.2,138.9,134.7,132.0,131.7,126.7(q),124.6,123.2,123.1,122.4(q),121.0,118.8,117.0,115.8,110.9,104.6,15.0。
1-(3-(4-氰基苯氧基)-4-甲基苯基)-3-(3-(三氟甲基)苯基)脲(1-(3-(4-cyanophenoxy)-4-methylphenyl)-3-(3-(trifluoromethyl)phenyl)urea；SC-134)
1H NMR(300MHz,DMSO-d 6 )：δ 9.04(s,1H),8.90(s,1H),7.96(s,1H),7.83(d,J=9.0Hz,2H),7.56~7.46(m,2H),7.35(d,J=2.1Hz,1H),7.31~7.27(m,2H),7.19(dd,J=8.1,2.1Hz,1H),7.02(d,J=9.0Hz,2H),2.05(s,3H),13C NMR(75MHz,DMSO-d 6 )：δ 161.1,152.4,152.0,140.4,139.1,134.7,131.9,129.9,129.3(q),124.2(q),122.9,121.9,118.8,118.2(q), 116.9,115.7,114.2(q),110.8,104.6,15.0。
1-(4-(氰基甲基)苯基)-3-(3-(4-氰基苯氧基)-4-甲基苯基)脲(1-(4-(cyanomethyl)phenyl)-3-(3-(4-cyanophenoxy)-4-methylphenyl)urea；SC-135)
1H NMR(300MHz,DMSO-d 6 )：δ 8.81(s,1H),8.76(s,1H),7.83(d,J=9.0Hz,2H),7.43(d,J=8.4Hz,2H),7.35(d,J=2.1Hz,1H),7.27(d,J=8.4Hz,1H),7.23(d,J=8.4Hz,2H),7.15(dd,J=8.4,2.1Hz,1H),7.02(d,J=9.0Hz,2H),3.93(s,2H),2.05(s,3H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.2,152.4,152.0,139.3,139.0,134.7,131.8,128.5,124.4,122.6,119.5,118.8,118.7,117.0,115.4,110.5,104.6,21.7,15.0。
1-(4-氯-3-(4-氰基苯氧基)苯基)-3-(4-氟-3-(三氟甲基)苯基)脲(1-(4-chloro-3-(4-cyanophenoxy)phenyl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea；SC-137)
1H NMR(300MHz,DMSO-d 6 )：δ 9.16(s,2H),7.94(dd,J=6.6,2.7Hz,1H),7.87(d,J=8.7Hz,2H),7.66~7.60(m,1H),7.56~7.53(m,2H),7.43(t,J=9.3Hz,1H),7.33(dd,J=9.3,2.7Hz,1H),7.09(d,J=8.7Hz,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.3,152.4,152.1,149.5,140.3,136.2(d),134.8,130.9,124.6(d),118.6,117.7,117.5,117.2,116.9,116.3(m),112.2,105.4。
1-(4-氯-3-(4-氰基苯氧基)苯基)-3-(3-(三氟甲基)苯基)脲 (1-(4-chloro-3-(4-cyanophenoxy)phenyl)-3-(3-(trifluoromethyl)phenyl)urea；SC-138)
1H NMR(300MHz,DMSO-d 6 )：δ 9.14(s,2H),7.96(s,1H),7.86(t,J=9.0Hz,2H),7.58~7.48(m,4H),7.35~7.31(m,2H),7.09(d,J=9.0Hz,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.4,152.3,149.5,140.3,140.2,134.8,130.9,129.9,129.5(q),124.2(q),122.1,118.6,118.4(q),117.7,117.2,116.8,114.4(q),112.2,105.4。
1-(4-氯-3-(4-氰基苯氧基)苯基)-3-(4-氯-3-(三氟甲基)苯基)脲(1-(4-chloro-3-(4-cyanophenoxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea；SC-139)
1H NMR(300MHz,DMSO-d 6 )：δ 9.27(s,1H),9.20(s,1H),8.05(s,1H),7.86(d,J=9.0Hz,2H),7.65-7.54(m,4H),7.34(dd,J=9.0,2.4Hz,1H),7.09(d,J=9.0Hz,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.3,152.2,149.5,140.1,139.0,134.8,132.0,130.9,126.5(q),123.4,122.8(q),122.7(q),118.6,117.2,117.1,117.0,116.9,112.3,105.4。
1-(4-氯-3-(4-氰基苯氧基)苯基)-3-(3-乙炔基苯基)脲(1-(4-chloro-3-(4-cyanophenoxy)phenyl)-3-(3-ethynylphenyl)urea；SC-140)
1H NMR(300MHz,DMSO-d 6 )：δ 9.06(s,1H),8.88(s,1H), 7.86(d,J=9.0Hz,2H),7.62(s,1H),7.55(s,1H),7.53(d,J=5.7Hz,1H),7.39(d,J=9.0Hz,1H),7.32~7.25(m,2H),7.12~7.07(m,3H),4.15(s,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.3,152.3,149.5,140.4,139.5,134.7,130.9,129.2,125.4,122.1,121.2,119.2,118.6,117.5,117.2,116.6,112.0,105.4,83.5,80.5。
1-(3,5-二(三氟甲基)苯基)-3-(2-氯-5-(4-氰基苯氧基)苯基)脲(1-(3,5-bis(trifluoromethyl)phenyl)-3-(2-chloro-5-(4-cyanophenoxy)phenyl)urea；SC-141)
1H NMR(300MHz,DMSO-d 6 )：δ 10.14(s,1H),8.61(s,1H),8.04(s,2H),7.99(d,J=2.7Hz,1H),7.85(d,J=8.4Hz,2H),7.67(s,1H),7.57(d,J=8.7Hz,1H),7.15(d,J=8.4Hz,2H),6.87(dd,J=8.7,3.0Hz,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.7,153.5,151.9,141.2,136.9,134.7,130.9(q),130.7,125.0(q),118.6,118.2,118.1,118.0,115.5,115.0(q),112.9,105.5。
1-(4-氯-3-(三氟甲基)苯基)-3-(2-氯-5-(4-氰基苯氧基)苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(2-chloro-5-(4-cyanophenoxy)phenyl)urea；SC-142)
1H NMR(300MHz,DMSO-d 6 )：δ 9.97(s,1H),8.56(s,1H),8.03(s,1H),8.00(d,J=3.0Hz,1H),7.86(d,J=8.7Hz,2H),7.61(s,2H), 7.56(d,J=8.7Hz,1H),7.16(d,J=8.7Hz,2H),6.86(dd,J=8.7,3.0Hz,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.7,153.5,151.9,138.7,137.1,134.7,132.2,130.7,126.8(q),123.1,122.9(q),122.7(q),118.7,118.2,117.8,116.8(q),115.2,112.5,105.4。
1-(2-氯-5-(4-氰基苯氧基)苯基)-3-(4-氟-3-(三氟甲基)苯基)脲(1-(2-chloro-5-(4-cyanophenoxy)phenyl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea；SC-143)
1H NMR(300MHz,DMSO-d 6 )：δ 9.84(s,1H),8.51(s,1H),8.01(d,J=2.7Hz,1H),7.95(dd,J=6.6,2.7Hz,1H),7.86(d,J=8.4Hz,2H),7.63~7.54(m,2H),7.44(t,J=9.8Hz,1H),7.15(d,J=8.4Hz,2H),6.85(dd,J=8.7,2.7Hz,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.7,155.5,153.5,152.2,152.0,137.2,135.9(d),134.7,130.6,124.3(d),118.6,118.7(q),118.2,117.9,117.7,116.6(q),116.0(q),115.0,112.4,105.5。
1-(5-(4-氰基苯氧基)-2-氟苯基)-3-(3-乙炔基苯基)脲(1-(5-(4-cyanophenoxy)-2-fluorophenyl)-3-(3-ethynylphenyl)urea；SC-144)
1H NMR(300MHz,DMSO-d 6 )：δ 9.23(s,1H),8.81(s,1H),7.98(dd,J=6.6,2.7Hz,1H),7.84(d,J=8.7Hz,2H),7.64(s,1H),7.39~7.27(m,3H),7.14~7.08(m,3H),6.80(dt,J=8.7,2.7Hz,1H),4.16(s,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.3,152.1,150.4,150.2(d),147.2,139.3,134.7,129.0(d),127.5(d),122.2,120.9,118.9,118.7,117.7,116.2(d),113.8 (d),111.9,105.1,83.4,80.5。
1-(5-(4-氰基苯氧基)-2-氟苯基)-3-(4-氟-3-(三氟甲基)苯基)脲(1-(5-(4-cyanophenoxy)-2-fluorophenyl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea；SC-145)
1H NMR(300MHz,DMSO-d 6 )：δ 9.46(s,1H),8.86(s,1H),7.96(dd,J=7.2,3.0Hz,2H),7.84(d,J=8.7Hz,2H),7.61~7.56(m,1H),7.44(t,J=10.0Hz,1H),7.40~7.33(m,1H),7.10(d,J=8.7Hz,2H),6.84(dt,J=9.0,3.0Hz,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.3,160.0,155.4(d),152.2(d),150.6,150.2(d),147.8,135.9(d),134.7,128.8(d),124.3(d),118.7(q),118.3(d),117.7,116.4(m),116.2(d),115.9(q),114.1(d),112.2(d),105.0。
1-(4-(氰基甲基)苯基)-3-(5-(4-氰基苯氧基)-2-氟苯基)脲(1-(4-(cyanomethyl)phenyl)-3-(5-(4-cyanophenoxy)-2-fluorophenyl)urea；SC-146)
1H NMR(300MHz,DMSO-d 6 )：δ 9.21(s,1H),8.78(s,1H),8.01(dd,J=6.6,2.7Hz,1H),7.84(d,J=8.4Hz,2H),7.44(d,J=8.4Hz,2H),7.38~7.31(m,1H),7.26(d,J=9.0Hz,2H),7.11(d,J=8.7Hz,2H),6.79(dt,J=8.7,3.3Hz,1H),3.95(s,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.3,151.9,150.3(d),147.1,138.5,134.7,129.1(d),128.7,124.8,119.1(d),118.6,117.7,116.3,116.0,113.6(d),111.7(d),105.0,21.7。
1-(3,5-二(三氟甲基)苯基)-3-(4-氯-3-(4-氰基苯氧基)苯基)脲 (1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-chloro-3-(4-cyanophenoxy)phenyl)urea；SC-148)
1H NMR(300MHz,DMSO-d 6 )：δ 9.50(s,1H),9.34(s,1H),8.10(s,2H),7.86(d,J=9.0Hz,2H),7.66(s,1H),7.71(d,J=5.4Hz,1H),7.56(s,1H),7.38(dd,J=9.0,2.4Hz,1H),7.09(d,J=9.0Hz,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.3,152.3,149.5,141.5,140.0,134.8,130.7(q),125.1(q),118.6,118.4,118.3,118.2,117.2,117.1,114.7(q),112.6,105.4。
1-(4-氯-3-(4-氰基苯氧基)苯基)-3-(4-(氰基甲基)苯基)脲(1-(4-chloro-3-(4-cyanophenoxy)phenyl)-3-(4-(cyanomethyl)phenyl)urea；SC-149)
1H NMR(300MHz,DMSO-d 6 )：δ 9.01(s,1H),8.83(s,1H),7.86(d,J=9.0Hz,2H),7.56(s,1H),7.53(d,J=8.7Hz,1H),7.44(d,J=8.4Hz,2H),7.30(dd,J=9.0,2.7Hz,1H),7.24(d,J=8.4Hz,2H),7.09(d,J=8.7Hz,2H),3.94(s,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.3,152.3,149.5,140.5,138.7,134.7,130.9,128.6,124.6,119.4,118.8,118.6,117.3,117.3,116.5,111.8,105.4,21.7。
1-(3-(4-氰基苯氧基)-4-氟苯基)-3-(3-乙炔基苯基)脲(1-(3-(4-cyanophenoxy)-4-fluorophenyl)-3-(3-ethynylphenyl)urea；SC-150)
1H NMR(300MHz,DMSO-d 6 )：δ 8.95(s,1H),8.85(s,1H),7.86(d,J=8.1Hz,2H),7.64(s,1H),7.53(dd,J=7.5,2.7Hz,1H),7.39(t,J=6.0Hz,2H),7.30~7.24(m,2H),7.14(d,J=8.7Hz,2H),7.08(d,J=7.5Hz,1H),4.15(s,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.6,152.4,150.3,147.1,140.5(d),139.7,137.1(d),134.7,129.2,125.3,122.1,121.2,119.1,118.6,117.5(d),117.0,116.3(d),112.6,105.5,83.5,80.4。
1-(3-(4-氰基苯氧基)-4-氟苯基)-3-(3-(三氟甲基)苯基)脲(1-(3-(4-cyanophenoxy)-4-fluorophenyl)-3-(3-(trifluoromethyl)phenyl)urea；SC-151)
1H NMR(300MHz,DMSO-d 6 )：δ 9.11(s,1H),9.02(s,1H),7.97(s,1H),7.86(d,J=8.7Hz,2H),7.85-7.47(m,3H),7.42-7.27(m,3H),7.14(d,J=8.7Hz,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.6,152.5,150.4,147.2,140.5(d),140.3,136.9(d),134.7,129.9,129.5(q),124.2(q),122.0,118.6,118.3(q),117.5(d),117.0,116.5(d),114.3(q),112.8,105.5。
1-(3,5-二(三氟甲基)苯基)-3-(3-(4-氰基苯氧基)-4-氟苯基)脲(1-(3,5-bis(trifluoromethyl)phenyl)-3-(3-(4-cyanophenoxy)-4-fluorophenyl)urea；SC-152)
1H NMR(300MHz,DMSO-d 6 )：δ 9.45(s,1H),9.21(s,1H),8.11(s,2H),7.86(d,J=9.0Hz,2H),7.64(s,1H),7.56(dd,J=7.2,2.4Hz, 1H),7.43~7.31(m,2H),7.14(d,J=9.0Hz,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.6,152.4,150.7,147.5,141.7,140.5(d),136.6(d),134.7,130.7(q),123.3(q),118.6,118.2(d),117.5(d),117.1,116.9,114.6(q),113.3,105.5。
1-(4-(氰基甲基)苯基)-3-(3-(4-氰基苯氧基)-4-氟苯基)脲(1-(4-(cyanomethyl)phenyl)-3-(3-(4-cyanophenoxy)-4-fluorophenyl)urea；SC-153)
1H NMR(300MHz,DMSO-d 6 )：δ 8.90(s,1H),8.81(s,1H),7.86(d,J=8.7Hz,2H),7.54(dd,J=7.8,2.7Hz,1H),7.44(d,J=8.4Hz,2H),7.37(t,J=9.6Hz,1H),7.28~7.23(m,3H),7.14(d,J=8.7Hz,2H),3.94(s,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.6,152.4,150.2,147.0,140.5(d),138.9,137.2(d),134.7,128.6,124.5,119.4,118.8,118.6,117.4(d),117.0,116.2(d),112.4,105.5,21.7。
1-(3-(4-氰基苯氧基)-4-氟苯基)-3-(4-氟-3-(三氟甲基)苯基)脲(1-(3-(4-cyanophenoxy)-4-fluorophenyl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea；SC-154)
1H NMR(300MHz,DMSO-d 6 )：δ 9.09(s,1H),9.02(s,1H),7.95(dd,J=6.6,2.7Hz,1H),7.86(d,J=8.7Hz,2H),7.66~7.60(m,1H),7.53(dd,J=7.2Hz,1H),7.46~7.27(m,3H),7.14(d,J=8.7Hz,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.6,155.4(q),152.6,152.1(q),150.4,147.2,140.5(d), 136.9(d),136.3(d),134.7,124.5(d),122.6(q),118.6,117.5(m),117.0,116.4(q),116.1(q),112.9,105.5。
6-(4-氰基苯氧基)-N-(4-氟-3-(三氟甲基)苯基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(6-(4-cyanophenoxy)-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-156)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.60~7.50(m,4H),7.16~7.10(m,3H),7.01(d,J=8.7Hz,1H),6.97(d,J=8.4Hz,2H),6.83(dd,J=9.0,2.7Hz,1H),4.32(t,J=4.5Hz,2H),3.95(t,J=4.5Hz,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 161.9,157.7(q),154.4(q),152.2,148.0,144.7,134.4,134.1(d),126.4,125.2(d),122.4(q),119.7,118.8,118.7,118.6,117.8,117.5,114.8,106.2,66.5,41.0。
N-(4-氯-3-(三氟甲基)苯基)-6-(4-氰基苯氧基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(N-(4-chloro-3-(trifluoromethyl)phenyl)-6-(4-cyanophenoxy)-2H-benZo[b][1,4]oxazine-4(3H)-carboxamide；SC-157)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.64(d,J=2.7Hz,1H),7.58(d,J=9.0Hz,2H),7.52(dd,J=9.0,2.7Hz,1H),7.40(d,J=9.0Hz,1H),7.17(s,1H),7.09(d,J=2.7Hz,1H),7.02(d,J=8.7Hz,1H),6.97(d,J=9.0 Hz,2H),6.84(dd,J=8.7,2.7Hz,1H),4.32(t,J=4.8Hz,2H),3.95(t,J=4.8Hz,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 161.9,151.9,148.0,144.7,136.9,134.4,132.2,129.0(q)126.7(q),126.3,123.7,122.6(q),119.8,118.7,118.6,118.5,117.5,114.8,106.2,66.5,41.0。
N-(3,5-二(三氟甲基)苯基)-6-(4-氰基苯氧基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(N-(3,5-bis(trifluoromethyl)phenyl)-6-(4-cyanophenoxy)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-158)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.83(s,2H),7.58(d,J=9.0Hz,2H),7.55(s,1H),7.34(s,1H),7.10(d,J=2.4Hz,1H),7.03(d,J=9.3Hz,1H),6.99(d,J=9.0Hz,2H),6.86(dd,J=9.0,2.7Hz,1H),4.33(t,J=4.5Hz,2H),3.97(t,J=4.5Hz,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 161.9,151.8,148.1,144.8,139.6,134.4,132.6(q),126.0,123.2(q),119.9,119.3(q),119.1,118.7,117.5,117.2(q),114.8,106.3,66.5,40.9。
6-(4-氰基苯氧基)-N-(3-(三氟甲基)苯基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(6-(4-cyanophenoxy)-N-(3-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-159)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.61(s,1H),7.58(d,J=9.0Hz,2H),7.51(d,J=7.8Hz,1H),7.40(t,J=7.8Hz,1H),7.31(d,J=7.8Hz, 1H),7.18(s,1H),7.11(d,J=2.7Hz,1H),7.01(d,J=9.0Hz,1H),6.97(d,J=9.0Hz,2H),6.83(dd,J=9.0,2.7Hz,1H),4.32(t,J=4.5Hz,2H),3.95(t,J=4.5Hz,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 162.0,152.1,148.0,144.6,138.5,134.4,131.6(q),129.7,126.4,123.9(q),122.7,120.6(q),119.7,118.8,118.6,117.5,116.4(q),114.8,106.1,66.5,40.9。
N-(4-(氰基甲基)苯基)-6-(4-氰基苯氧基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(N-(4-(cyanomethyl)phenyl)-6-(4-cyanophenoxy)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-160)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.57(d,J=9.0Hz,2H),7.34(d,J=8.7Hz,2H),7.24(d,J=8.7Hz,2H),7.12(d,J=3.0Hz,1H),7.10(s,1H),7.01(s,1H),6.97(d,J=9.0Hz,2H),6.81(dd,J=8.7,3.0Hz,1H),4.31(t,J=4.5Hz,2H),3.95(t,J=4.5Hz,2H),3.69(s,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 162.0,152.2,147.9,144.5,137.9,134.4,128.8,126.6,125.3,120.2,119.6,118.8,118.3,118.0,117.5,114.8,106.1,66.5,40.9,23.2。
6-(4-氰基苯氧基)-N-(3-乙炔基苯基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(6-(4-cyanophenoxy)-N-(3-ethynylphenyl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-161)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.60(d,J=9.0Hz,2H),7.44(d,J=8.1Hz,1H),7.33(s,1H),7.27~7.17(m,2H),7.09(d,J=3.0Hz, 1H),7.07(s,1H),7.00(d,J=8.7Hz,1H),6.98(d,J=9.0Hz,2H),6.83(dd,J=9.0,2.7Hz,1H),4.31(t,J=4.5Hz,2H),3.94(t,J=4.5Hz,2H),3.08(s,1H)；13C NMR(75MHz,CDCl3-d 1 )：δ 162.1,152.1,148.0,144.6,138.0,134.4,129.3,127.7,126.6,123.1,22.9,120.1,119.6,118.9,118.5,117.5,114.9,106.2,83.1,77.87,66.5,40.8。
7-(4-氰基苯氧基)-N-(3-乙炔基苯基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(7-(4-cyanophenoxy)-N-(3-ethynylphenyl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-162)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.62(d,J=9.0Hz,2H),7.47(d,J=9.0Hz,1H),7.45(s,1H),7.32(d,J=8.7Hz,1H),7.26~7.18(m,2H),7.11(s,1H),7.05(d,J=9.0Hz,2H),6.68(s,1H),6.65(d,J=2.7Hz,1H),4.31(t,J=4.5Hz,2H),3.94(t,J=4.5Hz,2H),3.04(s,1H)；13C NMR(75MHz,CDCl3-d 1 )：δ 161.1,153.1,152.4,148.7,138.2,134.4,129.3,127.6,124.1,123.0,123.9,122.8,120.2,118.8,118.4,112.7,110.1,106.6,83.2,77.7,67.0,40.6。
7-(4-氰基苯氧基)-N-(3-(三氟甲基)苯基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(7-(4-cyanophenoxy)-N-(3-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-163)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.67~7.57(m,4H),7.42(t,J =8.7Hz,1H),7.35~7.31(m,2H),7.23(s,1H),7.06(d,J=8.7Hz,2H),6.70(s,1H),6.68(dd,J=7.8,2.7Hz,1H),4.32(t,J=4.5Hz,2H),3.96(t,J=4.5Hz,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 161.1,153.3,152.4,148.8,138.7,134.4,131.6(q),129.7,124.1,124.0(q),122.7,122.6,120.4(q),118.8,118.5,116.3(q),112.8,110.1,106.7,67.0,40.7。
N-(3,5-二(三氟甲基)苯基)-7-(4-氰基苯氧基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(N-(3,5-bis(trifluoromethyl)phenyl)-7-(4-cyanophenoxy)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-164)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.89(s,2H),7.63(d,J=8.7Hz,2H),7.55(s,1H),7.40(s,1H),7.32(d,J=9.9Hz,1H),7.07(d,J=8.7Hz,2H),6.72(d,J=6.6,2.7Hz,1H),6.70(s,1H),4.33(t,J=4.5Hz,2H),3.97(t,J=4.5Hz,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 160.9,153.7,152.1,148.9,139.8,134.4,132.6(q),125.0(q),124.1,122.2,119.3(q),118.7,118.6,117.1(q),112.9,110.2,106.8,67.0,40.7。
N-(4-氯-3-(三氟甲基)苯基)-7-(4-氰基苯氧基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(N-(4-chloro-3-(trifluoromethyl)phenyl)-7-(4-cyanophenoxy)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-165)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.69(d,J=2.7Hz,1H),7.64~7.56(m,3H),7.42(d,J=8.4Hz,1H),7.31(d,J=9.3Hz,1H),7.23(s, 1H),7.06(d,J=8.7Hz,2H),6.71(s,1H),6.68(dd,J=6.9,2.7Hz,1H),4.32(t,J=4.8Hz,2H),3.95(t,J=4.8Hz,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 161.0,153.4,152.2,148.8,137.1,134.4,132.1,129.0(q),126.5(q),124.5(q),124.1,123.6,122.4,118.8,118.7,118.6,118.5,112.8,110.2,106.7,67.0,40.7。
7-(4-氰基苯氧基)-N-(4-氟-3-(三氟甲基)苯基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(7-(4-cyanophenoxy)-N-(4-fluoro-3-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-166)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.62(d,J=9.0Hz,2H),7.61~7.55(m,2H),7.32(d,J=9.3Hz,1H),7.17(s,1H),7.14(t,J=9.0Hz,1H),7.06(d,J=9.0Hz,2H),6.70(s,1H),6.67(dd,J=8.4,2.7Hz,1H),4.32(t,J=4.8Hz,2H),3.95(t,J=4.8Hz,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 161.1,157.6(d),154.3(d),153.4,152.5,148.8,134.4,134.3,134.3,125.1(d),124.1,122.5,122.4(q),118.8(q),118.5,117.6(d),112.8,110.2,106.7,67.0,40.7。
N-(4-(氰基甲基)苯基)-7-(4-氰基苯氧基)-2H-苯並[b][1,4]惡嗪-4(3H)-甲醯胺(N-(4-(cyanomethyl)phenyl)-7-(4-cyanophenoxy)-2H-benzo[b][1,4]oxazine-4(3H)-carboxamide；SC-167)
1H NMR(300MHz,CDCl3-d 1 )：δ 7.61(d,J=8.7Hz,2H), 7.40(d,J=8.7Hz,2H),7.33(d,J=8.4Hz,1H),7.25(d,J=9.0Hz,2H),7.15(s,1H),7.05(d,J=9.0Hz,2H),6.68(s,1H),6.65(dd,J=8.4,2.7Hz,1H),4.31(t,J=4.2Hz,2H),3.94(t,J=4.2Hz,2H),3.69(s,2H)；13C NMR(75MHz,CDCl3-d 1 )：δ 161.1,153.1,152.5,148.7,138.1,134.4,128.8,125.1,124.1,122.8,120.2,118.8,118.4,118.0,112.8,110.1,106.6,67.0,40.7,23.2。
1-(4-(4-(氰基甲基)苯氧基)苯基)-3-(4-氟-3-(三氟甲基)苯基)脲(1-(4-(4-(cyanomethyl)phenoxy)phenyl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea；SC-168)
1H NMR(300MHz,DMSO-d 6 )：δ 9.02(s,1H),8.82(s,1H),8.01(dd,J=6.6,2.7Hz,1H),7.67~7.61(m,1H),7.48(d,J=9.0Hz,2H),7.43(t,J=9.3Hz,1H),7.34(d,J=9.0Hz,2H),6.99(dd,J=9.0,3.9Hz,4H),4.00(s,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 157.0,155.2(d),152.7,151.9(d),150.8,136.6(d),135.4,129.7,125.5,124.4(q),124.2(d),120.4,119.7,119.4,118.1,117.6(d),116.4(m),115.9(q),21.6。
1-(4-(4-(氰基甲基)苯氧基)苯基)-3-(4-(氰基甲基)苯基)脲(1-(4-(4-(cyanomethyl)phenoxy)phenyl)-3-(4-(cyanomethyl)phenyl)urea；SC-169)
1H NMR(300MHz,DMSO-d 6 )：δ 8.73(s,1H),8.71(s,1H),7.47(d,J=9.0Hz,4H),7.33(d,J=9.0Hz,2H),7.25(d,J=9.0Hz,2H),6.99(d,J=9.0,3.0Hz,4H),3.99(s,2H),3.94(s,2H)；13C NMR(75MHz, DMSO-d 6 )：δ 157.1,152.6,150.5,139.2,135.8,129.7,128.6,125.5,124.2,120.0,119.8,119.5,119.4,118.5,118.0,21.7,21.6。
1-(4-(4-(氰基甲基)苯氧基)苯基)-3-(3-乙炔基苯基)脲(1-(4-(4-(cyanomethyl)phenoxy)phenyl)-3-(3-ethynylphenyl)urea；SC-170)
1H NMR(300MHz,DMSO-d 6 )：δ 8.78(s,1H),8.75(s,1H),7.66(s,1H),7.48(d,J=9.0Hz,2H),7.40(d,J=8.4Hz,1H),7.34(d,J=9.0Hz,2H),7.29(d,J=8.4Hz,1H),7.07(d,J=8.4Hz,1H),6.99(dd,J=9.0,3.0Hz,4H),4.15(s,1H),3.99(s,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 157.1,152.5,150.6,140.0,135.6,129.7,129.2,125.5,125.0,122.0,120.9,120.1,119.8,119.4,118.9,118.0,83.6,80.4,21.6。
1-(4-氯-3-(三氟甲基)苯基)-3-(4-(4-(氰基甲基)苯氧基)苯基)脲(1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(4-(cyanomethyl)phenoxy)phenyl)urea；SC-171)
1H NMR(300MHz,DMSO-d 6 )：δ 9.15(s,1H),8.87(s,1H),8.11(d,J=2.4Hz,1H),7.66~7.59(m,2H),7.49(d,J=9.0Hz,2H),7.34(d,J=9.0Hz,2H),7.00(d,J=9.0,4.2Hz,4H),4.00(s,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 157.0,152.5,150.9,139.4,135.3,132.0,129.7,126.7(q),125.6,122.8(q),123.0,122.2(q),120.5,119.7,119.4,118.1,116.8(q),21.6。
1-(3,5-二(三氟甲基)苯基)-3-(4-(4-(氰基甲基)苯氧基)苯基)脲(1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-(4-(cyanomethyl)phenoxy) phenyl)urea；SC-172)
1H NMR(300MHz,DMSO-d 6 )：δ 9.39(s,1H),9.02(s,1H),8.14(s,2H),7.63(s,1H),7.51(d,J=9.0Hz,2H),7.34(d,J=9.0Hz,2H),7.01(dd,J=9.0,4.8Hz,4H),4.00(s,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 157.0,152.5,151.1,141.9,135.1,130.9(q),129.8,125.6,123.3(q),120.8,119.7,119.4,118.2,117.9(q),114.2(q),21.6。
1-(4-(4-(氰基甲基)苯氧基)苯基)-3-(3-(三氟甲基)苯基)脲(1-(4-(4-(cyanomethyl)phenoxy)phenyl)-3-(3-(trifluoromethyl)phenyl)urea；SC-173)
1H NMR(300MHz,DMSO-d 6 )：δ 9.05(s,1H),8.84(s,1H),8.01(s,1H),7.54(t,J=9.3Hz,2H),7.49(d,J=9.0Hz,2H),7.36~7.29(m,3H),7.00(dd,J=9.0,3.9Hz,4H),4.00(s,2H)；13C NMR(75MHz,DMSO-d 6 )：δ 157.1,152.6,150.8,140.6,135.5,130.1(q),129.9,129.7,129.3,125.5,124.2(q),121.8,120.3,119.8,119.4,118.1,114.1(q),21.6。
1-(4-氯-3-(4-氰基-3-甲基苯氧基)苯基)-3-(3-(三氟甲基)苯基)脲(1-(4-chloro-3-(4-cyano-3-methylphenoxy)phenyl)-3-(3-(trifluoromethyl)phenyl)urea；SC-174)
1H NMR(300MHz,DMSO-d 6 )：δ 9.14(s,1H),9.13(s,1H),7.96(s,1H),7.77(d,J=8.7Hz,1H),7.58~7.47(m,4H),7.35~7.30(m,2H),7.04(d,J=2.1Hz,1H),6.86(dd,J=8.7,2.7Hz,1H),2.45(s,3H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.2,152.3,149.6,144.5,140.2,140.1,134.8,130.8,129.9,129.5(q),124.1(q),122.1,118.4(q),118.0,117.8,117.7,116.7,114.5,114.4(q),112.1,106.1,20.0。
1-(4-氯-3-(4-氰基-3-甲基苯氧基)苯基)-3-(4-氯-3-(三氟甲基)苯基)脲(1-(4-chloro-3-(4-cyano-3-methylphenoxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea；SC-175)
1H NMR(300MHz,DMSO-d 6 )：δ 9.26(s,1H),9.18(s,1H),8.05(d,J=2.4Hz,1H),7.77(d,J=8.4Hz,1H),7.65(s,1H),7.64(s,1H),7.54(d,J=8.4Hz,1H),7.51(d,J=2.7Hz,1H),7.34(dd,J=8.7,2.4Hz,1H),7.04(d,J=2.4Hz,1H),6.87(dd,J=8.7,2.7Hz,1H),2.45(s,3H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.1,152.2,149.6,144.6,140.1,139.0,134.9,132.0,130.9,126.7(q),123.4,122.8(q),122.7,118.0,117.9,117.8,117.1(q),116.8,114.5,112.3,106.1,20.0。
1-(3,5-二(三氟甲基)苯基)-3-(4-氯-3-(4-氰基-3-甲基苯氧基)苯基)脲(1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-chloro-3-(4-cyano-3-methylphenoxy)phenyl)urea；SC-176)
1H NMR(300MHz,DMSO-d 6 )：δ 9.48(s,1H),9.32(s,1H),8.11(s,2H),7.77(d,J=8.4Hz,1H),7.65(s,1H),7.55(d,J=8.4Hz,1H),7.53(s,1H),7.38(dd,J=9.0,2.7Hz,1H),7.04(d,J=2.4Hz,1H),6.87(dd,J=8.4,2.4Hz,1H),2.45(s,3H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.2,152.3,149.6,144.5,141.5,139.9,134.8,130.9,130.7(q),123.3(q),118.3(q),118.2,117.9,117.8,117.1,114.7(q),114.5,112.6,106.1,20.0。
1-(4-氯-3-(4-氰基-3-甲基苯氧基)苯基)-3-(4-氟-3-(三氟甲基)苯基)脲(1-(4-chloro-3-(4-cyano-3-methylphenoxy)phenyl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea；SC-177)
1H NMR(300MHz,DMSO-d 6 )：δ 9.13(s,1H),9.11(s,1H),7.95(dd,J=6.6,2.4Hz,1H),7.77(d,J=8.4Hz,1H),7.66~7.60(m,1H),7.53(d,J=8.4Hz,1H),7.51(s,1H),7.42(t,J=9.9Hz,1H),7.33(dd,J=8.4,2.4Hz,1H),7.03(d,J=2.4Hz,1H),6.87(dd,J=8.4,2.7Hz,1H),2.45(s,3H)；13C NMR(75MHz,DMSO-d 6 )：δ 160.1,155.4(d),152.4,152.2(d),149.6,144.5,140.2,136.2(d),134.8,130.8,124.6(d),122.6(q),118.0,117.8,117.7,117.4,116.7(m),116.3(q),114.5,112.2,106.1,20.0。
1-(4-氯-3-(3-氯-4-氰基苯氧基)苯基)-3-(3-(三氟甲基)苯基)脲(1-(4-chloro-3-(3-chloro-4-cyanophenoxy)phenyl)-3-(3-(trifluoromethyl)phenyl)urea；SC-178)
1H NMR(300MHz,DMSO-d 6 )：δ 9.18(s,1H),9.17(s,1H), 7.99~7.96(m,2H),7.61~7.55(m,3H),7.51(t,J=7.8Hz,1H),7.38~7.31(m,3H),7.03(dd,J=8.7,2.7Hz,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.0,152.3,148.9,140.4,140.2,137.3,136.4,131.0,129.9,129.5(q),124.2(q),122.1,118.4(q),117.8,117.6,117.3,115.9,115.7,114.4(q),112.3,106.1。
1-(4-氯-3-(3-氯-4-氰基苯氧基)苯基)-3-(4-氯-3-(三氟甲基)苯基)脲(1-(4-chloro-3-(3-chloro-4-cyanophenoxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea；SC-179)
1H NMR(300MHz,DMSO-d 6 )：δ 9.31(s,1H),9.24(s,1H),8.07(s,1H),7.98(d,J=8.7Hz,1H),7.66~7.56(m,4H),7.39~7.35(m,2H),7.03(dd,J=8.7,2.4Hz,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.0,152.2,148.9,140.2,139.0,137.3,136.4,132.0,131.0,126.7(q),123.4,122.8(q),122.7(q),117.8,117.7,117.4,117.0(q),115.8,115.7,112.4,106.2。
1-(3,5-二(三氟甲基)苯基)-3-(4-氯-3-(3-氯-4-氰基苯氧基)苯基)脲(1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-chloro-3-(3-chloro-4-cyanophenoxy)phenyl)urea；SC-180)
1H NMR(300MHz,DMSO-d 6 )：δ 9.52(s,1H),9.37(s,1H),8.11(s,2H),7.97(d,J=8.7Hz,1H),7.66(s,1H),7.61(d,J=2.4Hz,1H),7.58(d,J=8.7Hz,1H),7.41(dd,J=8.7,2.4Hz,1H),7.38(d,J=2.4Hz,1H),7.03(dd,J=8.7,2.4Hz,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.0,152.3,148.9, 141.5,140.1,137.3,136.4,131.0,130.7(q),123.3(q),118.3(q),118.1,117.8,117.7,115.9,115.6,114.8(q),112.8,106.2。
1-(4-氯-3-(3-氯-4-氰基苯氧基)苯基)-3-(4-氟-3-(三氟甲基)苯基)脲(1-(4-chloro-3-(3-chloro-4-cyanophenoxy)phenyl)-3-(4-fluoro-3-(trifluoromethyl)phenyl)urea；SC-181)
1H NMR(300MHz,DMSO-d 6 )：δ 9.19(s,1H),9.17(s,1H),7.99~7.94(m,2H),7.66~7.61(m,1H),7.59(d,J=2.4Hz,1H),7.56(d,J=8.7Hz,1H),7.43(t,J=9.6Hz,1H),7.38~7.35(m,2H),7.02(dd,J=8.7,2.4Hz,1H)；13C NMR(75MHz,DMSO-d 6 )：δ 161.0,155.4(d),152.4,152.1(d),148.9,140.4,137.3,136.4,136.2(d),131.0,124.6(d),122.6(q),117.8,117.7,117.6,117.5,117.3,116.2(q),115.9,115.7,112.4,106.2。
1-(3,5-二(三氟甲基)苯基)-3-(4-氯-3-((6-氰基吡啶-3-基)甲氧基)苯基)脲(1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-chloro-3-((6-cyanopyridin-3-yl)oxy)phenyl)urea；SC-182)
1H NMR(400MHz,CDCl3)：δ 8.40(d,J=2.4Hz,1H),8.08(dd,J=6.6,2.4Hz,1H),7.89(s,2H),7.64(s,1H),7.62(s,1H),7.53(s,1H),7.36(s,1H),7.26(dd,J=8.4,2.4Hz,1H),7.13(t,J=9.6Hz,1H),6.72(t,J=4.8Hz,1H)。
1-(3,5-二(三氟甲基)苯基)-3-(5-((6-氰基吡啶-3-基)甲氧 基)-2-氟苯基)脲(1-(3,5-bis(trifluoromethyl)phenyl)-3-(5-((6-cyanopyridin-3-yl)oxy)-2-fluorophenyl)urea；SC-183)
1H NMR(400MHz,CDCl3)：δ 8.40(d,J=2.4Hz,1H),8.08(dd,J=6.6,2.4Hz,1H),7.89(s,2H),7.64(s,1H),7.62(s,1H),7.53(s,1H),7.36(s,1H),7.26(dd,J=8.4,2.4Hz,1H),7.13(t,J=9.6Hz,1H),6.72(t,J=4.8Hz,1H)。
生物活性分析 重組SHP-1中SC衍生物之磷酸酶活性
利用RediPlate 96 EnzChek酪胺酸磷酸酶分析套組(R-22067)做SHP-1活性分析(分子探針)。重組SHP-1蛋白(25ng)與1μM的SC衍生物反應2小時。然後SHP-1磷酸酶活性分析係根據原廠說明書進行，並且於波長465nm測定其吸光度。SC衍生物之SHP-1活性顯示於下列表7。控制組為DMSO，其為SC衍生物之溶劑。數值以平均值±SD表示(N=3)。
SC衍生物之細胞毒性
將PLC5細胞(一種肝癌細胞株)以5x103個細胞每孔的密度植入96孔盤中。然後，細胞暴露於指定濃度的SC衍生物72小時。之後，細胞與MTT(1mg/ml)(Sigma-Aldrich,St.Louis,MO)於37℃培養2小時。利用微量盤式分析儀在波長570nm測量吸光率，以評估細胞存活率。SC衍生物對於 PLC5癌細胞株的IC50(半數最大抑制濃度)亦顯示於下表7。
在不脫離本發明之精神與範圍下，本發明所屬領域中具有通 常知識者能夠容易地做出不同的結構上修飾與變化。因此，本發明後述申請專利範圍涵蓋這些不脫離本發明之精神與範圍的結構上修飾與變化。

Claims (21)

  1. 一種化合物，具有下列化學結構式I： 其中n為0或1；X為N或C-R1；R1為H或Cl；R2與R3各自獨立為H、一鹵素或一烷基，其中當n=0時，R2與R3不同時為H；Ar為一經取代或未取代的伸苯基(phenylene group)、或一伸萘基(naphthalenylene group)，其中該經取代的伸苯基為或，且該伸萘基為；R4為H、一鹵素、或一烷基；R5為H、一鹵素、一烷基、一烷氧基、或一羥基；R6為H或一羥基；以及R7為一未取代或經取代的芳香基。
  2. 如申請專利範圍第1項所述之化合物，其中該R2與R3之鹵素各自獨立為F、Cl或Br。
  3. 如申請專利範圍第1項所述之化合物，其中該R4與R5之鹵素各自獨立為F 或Cl。
  4. 如申請專利範圍第1項所述之化合物，其中該R2、R3、R4及R5之烷基各自獨立為CH3或CH2CH3。
  5. 如申請專利範圍第1項所述之化合物，其中R2與R3共同形成一二價基團。
  6. 如申請專利範圍第5項所述之化合物，其中該二價基團為。
  7. 如申請專利範圍第1項所述之化合物，其中R5與R6形成一二價基團。
  8. 如申請專利範圍第7項所述之化合物，其中該二價基團為。
  9. 如申請專利範圍第1項所述之化合物，其中R7為一經取代的苯基、一經取代的、、或。
  10. 如申請專利範圍第9項所述之化合物，其中該經取代的苯基為
  11. 如申請專利範圍第9項所述之化合物，其中該經取代的
  12. 一種化合物，具有下列化學結構式II： 其中R2與R3為H，且Ar為一芳香基。
  13. 如申請專利範圍第12項所述之化合物，其中該芳香基為或。
  14. 一種化合物，具有下列化學結構式III： 其中R8為一鹵烷基或一經取代的苯氧基(C6H5O-)；R9為H、一鹵素、或一烷基；以及X為、或。
  15. 如申請專利範圍第14項所述之化合物，其中該鹵烷基為CF3。
  16. 如申請專利範圍第14項所述之化合物，其中該經取代的苯氧基為
  17. 如申請專利範圍第14項所述之化合物，其中該鹵素為Cl。
  18. 如申請專利範圍第14項所述之化合物，其中該烷基為CH3或CH2CH3。
  19. 一種化合物，具有下列化學結構式：
  20. 一種醫藥組成物，包含一有效劑量的如申請專利範圍第1項至第19項中任一項所述之化合物。
  21. 如申請專利範圍第20項所述之醫藥組成物，進一步包含一藥學上可接受之載體。
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