TW202315871A - 作為造血前驅細胞激酶１（ｈｐｋ１）抑制劑的吲唑及其使用方法 - Google Patents
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Abstract
本發明提供式(I)所示化合物或其藥學上可接受的鹽、包含該化合物的組成物、使用該化合物治療與HPK1相關的各種疾病之方法及製備此等化合物之方法。
Description
本發明關於造血前驅細胞激酶1(HPK1)抑制劑、包含該抑制劑之藥物組成物、使用該抑制劑治療與HPK1相關的各種疾病之方法及製備此等化合物之方法。
免疫療法係一種利用人體自身免疫系統來對抗癌症及其他疾病 之治療方法。近年來，此種相對較新之方法，在臨床治療多種腫瘤類型方面取得顯著的成功，特別是在免疫檢查點抑制劑之治療及嵌合抗原T細胞療法方面。研究最多的檢查點抑制劑，包含CTLA4、PD-1或PD-L1抑制劑，其藉由克服腫瘤部位之免疫抑制機制，顯示出顯著的抗腫瘤活性。
造血前驅細胞激酶1(HPK1，MAP4K1)是一種絲胺酸/蘇胺酸激酶，屬於MAP4K的成員。HPK1在造血細胞系的亞群中顯著表達。最新發現HPK1是活化T淋巴細胞及樹突狀細胞的關鍵負調節因子。最近的研究表明，HPK1激酶活性在抗癌免疫中作為新細胞內檢查點分子扮演重要的角色，及與現有檢查點方案聯合療法之潛在優勢。抑制HPK1預計具有雙重的功能，1.延長活化T細胞的時間；2藉由樹突狀細胞增加APC的功能。此種雙重靶向可協同作用，以在腫瘤微環境中達到有效的免疫反應。因此，HPK1已被證實為抗癌免疫治療的新目標。可使用本發明化合物治療的癌症示例包含但不限於，所有形式的癌症、黑素瘤、母細胞瘤、肉瘤、淋巴瘤及白血病，淋巴瘤及白血病，包含但不限於膀胱癌、腦瘤、乳腺癌、子宮頸癌、大腸直腸癌、食道癌、子宮內膜癌、肝細胞癌、喉癌、肺癌、骨肉瘤、卵巢癌、胰腺癌、前列腺癌、腎癌和甲狀腺癌、急性淋巴球白血病、急性骨髓性白血病、室管膜瘤、尤文氏肉瘤、神經膠母細胞瘤、髓母細胞瘤、 神經胚細胞瘤、橫紋肌肉瘤、橫紋肌樣癌及腎胚細胞瘤(威爾姆氏腫瘤)。
用小分子抑制劑抑制HPK1可用於治療癌症及其他疾病(Hernandez, S., et. al. (2018) Cell Reports 25, 80-94)。
［先前技術文獻］
［專利文獻］無
本發明提供一種新型吲唑化合物及藥學上可接受的鹽，作為有效HPK1抑制劑及T細胞與樹突狀細胞之雙重活化劑。
本發明之一實施例是由式(I)所示之化合物：
式(I)
或其藥學上可接受的鹽、水合物、溶劑化物，其中，R
1、R
1、R
3、R
4、R
5、Het、M及L如具體實施方式中所定義。
在另一實施例中，本發明提供一種藥物組成物，其包含藥學上可接受之載體或稀釋劑及式(I)所示化合物或其藥學上可接受的鹽。
在另一實施例中，本發明提供一種治療患有與HPK1調節相關疾病或病症的受試者之方法，包含：向受試者施用治療有效量之式(I)所示化合物或其藥學上可接受的鹽。
下述描述僅為示例性的，並無意於限制本發明、應用或用途。
定義
為清楚起見，本說明書在此定義本發明中所使用之通用術語。
本說明書可互換地使用術語「取代基」、「自由基」、「基團」、「部分」及「片段」。
如本說明書所用，術語「烯基」係指具有至少一個不飽和位點，即碳-碳，sp2雙鍵之直鏈或支鏈的烴基。在一實施例中，烯基具有2至12個碳原子。在一些實施例中，烯基為C
2~C
10烯基或C
2~C
6烯基。烯基的實例包含但不限於乙烯或乙烯基(-CH＝CH
2)、烯丙基(-CH
2CH＝CH
2)、環戊烯基(-C
5H
7)及5-己烯基(-CH
2CH
2CH
2CH
2CH＝CH
2)。
如本說明書所用，術語「烷氧基」為RO-，其中R為烷基。烷氧基之非限制性實例包含甲氧基、乙氧基及丙氧基。
如本說明書所用，術語「烷氧基烷基」係指被烷氧基取代之烷基部分。烷氧基烷基之實例包含甲氧基甲基、甲氧基乙基、甲氧基丙基及乙氧基乙基。
如本說明書所用，術語「烷氧羰基」為ROC(O)-，其中，R為如本發明所定義之烷基。在各種實施例中，R為C
1~C
10烷基或C
1~C
6烷基。
如本說明書所用，術語「烷基」係指直鏈或支鏈之烴基。在一實施例中，烷基具有1至12個碳原子。在一些實施例中，烷基為C
1~C
10烷基或C
1~C
6烷基。烷基之實例包含但不限於甲基、乙基、丙基、異丙基、丁基、異丁基、叔丁基、戊基、己基、庚基、辛基、壬基及癸基。「低級烷基」係指具有1至4個碳原子的烷基。
如本說明書所用，若使用術語「C
1~C
6」，則表示碳原子數為1至6。例如：C
1~C
6烷基表示碳數為1至6之任何整數的烷基。
如本說明書所用，術語「烷基胺基」係指被一個或多個烷基取代的胺基。「N-(烷基)胺基」是RNH-，且「N,N-(烷基)
2胺基」是R
2N-，其中R基團是本說明書所定義之烷基且其相同或不同。在各種實施例中，R為C
1~C
10烷基或C
1~C
6烷基。烷基胺基之實例包含甲基胺基、乙基胺基、丙基胺基、丁基胺基、二甲基胺基、二乙基胺基及甲基乙基胺基。
如本說明書所用，術語「烷基胺基烷基」係指被烷基胺基取代之烷基部分，其中烷基胺基如本說明書所定義。烷基胺基烷基之實例包含甲基胺基甲基及乙基胺基甲基。
如本說明書所用，術語「炔基」係指具有至少一個不飽和位點，即碳-碳，sp三鍵之直鏈或支鏈碳鏈基團。在一實施例中，炔基具有2至12個碳原子。在一些實施例中，炔基為C
2~C
10炔基或C
2~C
6炔基。炔基之實例包含炔基(-C≡CH)和炔丙基(-CH
2C≡CH)。
如本說明書所用，術語「芳基」係指每個環中至多7個原子的任何單環或雙環碳環，其中至少一個環是芳族的，或5至14個碳原子的芳環系統是，該芳環系統為包含與5或6元環烷基稠合之碳環芳族基團。芳基的代表性實例包含但不限於苯基、甲苯基、二甲苯基、萘基、四氫萘基、蒽基、芴基、茚基、薁基及二氫茚基。碳環芳族基團可為未取代的或任選取代的。
如本說明書所用，術語「環烷基」是包含至少一個飽和或部分不飽和之環結構且藉由環碳連接之烴基。在各種實施例中，其係指飽和或部分不飽和之C
3~C
12環狀部分，飽和或部分不飽和之C
3~C
12環狀部分之實例包含環丙基、環丁基、環戊基、環戊烯基、環己基、環己烯基、環庚基及環辛基。「環烷氧基」是RO-，其中，R是環烷基。
如本說明書所用，術語「鹵素」及「鹵代」係指氯(-Cl)、溴(-Br)、氟(-F)或碘(-I)。「鹵代烷氧基」係指被一個或多個鹵素基團取代的烷氧基，且鹵代烷氧基之實例包含但不限於-OCF
3、-OCHF
2及-OCH
2F。「鹵代烷氧基烷基」係指被鹵代烷氧基取代之烷基部分，其中鹵代烷氧基如本說明書所定義。鹵代烷氧基烷基之實例包含三氟甲氧基甲基、三氟乙氧基甲基及三氟甲氧基乙基。「鹵代烷基」係指被一個或多個鹵素基團取代的烷基部分。鹵代烷基的實例包含-C
F3及-CHF
2。
如本說明書所用，術語「雜烷基」係指在鏈中具有2至14個碳(在一些實施例中為2至10個碳)之直鏈或支鏈烷基，其中，一個或多個已被雜原子取代，該雜原子選自S、O、P及N。示例性的雜烷基包含烷基醚、二級及三及烷基胺、醯胺、烷基硫化物等。
如本說明書所用，術語「雜環基」包含以下定義之雜芳基，且係指具有2至14個環碳原子之飽和或部分不飽和的單環、雙環或三環基團，除環碳原子外，還有1至4個選自P、N、O及S之雜原子。在各個實施例中，雜環基藉由碳或藉由雜原子連接至另一部分，且任選地被碳或雜原子取代。雜環基的實例包含氮雜環丁烷基、苯並咪唑基、苯並呋喃基、苯並呋喃氮基、苯並吡唑基、苯並三唑基、苯並噻吩基、苯並噁唑基、咔唑基、咔啉基、肉桂啉基、呋喃基、咪唑基、二氫吲哚基、吲哚基、吲哚嗪基、吲唑基、異苯並呋喃基、異吲哚基、異喹啉基、異噻唑基、異噁唑基、萘吡啶基、噁二唑基、噁唑基、噁唑啉、異噁唑啉、氧雜環丁烷基、吡喃基、吡嗪基、吡唑基、噠嗪基、吡啶並吡啶基、吡啶基、嘧啶基、吡咯基、喹唑啉基、喹啉基、喹㗁啉基、四氫吡喃基、四氫硫吡喃基、四氫異喹啉基、四唑基、四唑並吡啶基、噻二唑基、噻唑基、噻吩基、三唑基、氮雜環丁烷基、1,4-二噁烷基、六氫氮雜吡啶基、哌嗪基、哌啶基、吡啶-2-基、吡咯烷基、嗎啉基、硫代嗎啉基、二氫苯並咪唑基、二氫苯並呋喃基、二氫苯並噻吩基、二氫苯並噁唑基、二氫呋喃基、二氫咪唑基、二氫吲哚基、二氫異噁唑基、二氫異噻唑基、二氫噁二唑基、二氫噁唑基、二氫吡嗪基、二氫吡唑基、二氫吡啶基、二氫嘧啶基、二氫吡咯基、二氫喹啉基、二氫四唑基、二氫噻二唑基、二氫噻唑基、二氫噻吩基、二氫三唑基、二氫氮雜環丁烷基、亞甲二氧苯甲醯基、四氫呋喃基及四氫噻吩基及其N-氧化物。「雜環基氧基」是RO-，其中，R是雜環基。「雜環硫基」是RS-，其中，R是雜環基。
如本說明書所用，術語「3-元或4-元雜環基」係指具有3或4個環原子之單環，其中，至少一個環原子是選自N、O及S之雜原子組成之群組。3-或4-元雜環基之非限制性實例包含氮丙啶基、2
H-氮丙烯基、氧雜環烷基、噻喃基、氮雜環丁烷基、2,3-二乙醯氮、氮雜基、1,3-二氮雜環丁烷基、氧雜環丁烷基、2
H-氧雜環丁烷基、硫雜環丁烷基及2
H-噻吩基。
如本說明書所用，術語「雜芳基」係指在每個環中具有至多7個原子之單環、雙環或三環，其中至少一個環是芳族且在環中包含1至4個選自N、O及S之雜原子組成之群組。雜芳基的非限制性實例包含吡啶基、噻吩基、呋喃基、嘧啶基、咪唑基、吡喃基、吡唑基、噻唑基、噻二唑基、異噻唑基、噁唑基、異噁唑基、吡咯基、噠嗪基、吡嗪基、喹啉基、異喹啉基、苯並呋喃基、二苯並呋喃基、二苯並噻吩基、苯並噻吩基、吲哚基、苯並噻唑基、苯並噁唑基、苯並咪唑基、異吲哚基、苯並三唑基、嘌呤基、硫雜茚基及吡嗪基。雜芳基的連接可藉由芳環產生，或者，若雜芳基是雙環或三環且其中一個環非為芳族或不包含雜原子，則可藉由非芳族環或不包含雜原子之環進行連接。「雜芳基」亦應理解為包含任何含氮雜芳基之N-氧化物衍生物。「雜芳氧基」是RO-，其中，R是雜芳基。
如本說明書所用，術語「羥基烷氧基」係指被羥基(-OH)取代之烷氧基，其中，烷氧基如本說明書所定義。羥基烷氧基之實例是羥基乙氧基。
如本說明書所用，術語「羥烷基」係指被至少一個羥基取代之直鏈或支鏈的單價C
1~C
10烴基，且羥烷基之實例包含但不限於羥甲基、羥乙基、羥丙基及羥丁基。
如本說明書所用，術語「藥學上可接受的」是指適用於藥物製劑，對此用途而言一般認為是安全的，且已由國家或州政府的監管機構正式批准用於該用途，或被列入《美國藥典》或其他公認供動物使用，特別是供人類使用之藥典中。
如本說明書所用，術語「藥學上可接受之載體」係指稀釋劑、佐劑、賦形劑或載體，或藥學上可接受的且與本發明化合物一起施用之其他成分。
如本說明書所用，術語「藥學上可接受的鹽」係指可增強所需藥理活性的鹽。藥學上可接受的鹽之實例包含與無機或有機酸形成之酸加成鹽、金屬鹽及胺鹽。與無機酸形成之酸加成鹽的實例包含與鹽酸、氫溴酸、硫酸、硝酸及磷酸形成的鹽。與有機酸形成的酸加成鹽之實例包含乙酸、丙酸、己酸、庚酸、環戊烷丙酸、乙醇酸、丙酮酸、乳酸、丙二酸、丁二酸、蘋果酸、順丁烯二酸、反丁烯二酸、酒石酸、檸檬酸、苯甲酸、鄰-(4-羥基-苯甲醯基)-苯甲酸、肉桂酸、苦杏仁酸、甲磺酸、乙磺酸、1,2-乙二磺酸、2-羥乙磺酸、苯磺酸、對氯苯磺酸、2-萘磺酸、對甲苯磺酸、樟腦磺酸、4-甲基-雙環[2.2.2]辛-2-烯-1-羧酸、葡萄糖庚酸、4,4'-亞甲基雙(3-羥基-2-萘)酸、3-苯基丙酸、三甲基乙酸、叔丁基乙酸、月桂基硫酸、葡萄糖酸、麩胺酸、羥基萘甲酸、水楊酸、硬脂酸及黏康酸。金屬鹽之實例包含與鈉、鉀、鈣、鎂、鋁、鐵及鋅離子的鹽。胺鹽之實例包含與與胺及有機含氮鹼形成之鹽，其強度足以與羧酸形成鹽。
如本說明書所用，術語「被取代」指上述任何基團(即烷基、芳基、雜芳基、雜環或環烷基)，其中，被取代部分的至少一個氫原子被取代基取代。在一實施例中，被取代之基團的每個碳原子被不超過兩個取代基取代。在另一實施例中，被取代之基團的每個碳原子被不多於一個取代基取代。在酮取代基的情況下，兩個氫原子被氧取代，氧藉由雙鍵連接到碳上。除非特別規定，否則取代基包含鹵代、羥基、(低級)烷基、鹵代烷基、單烷基或二烷基胺基、芳基、雜環、-NO
2、B(OH)
2、BPin、-NR
aR
b、-NR
aC(=O)R
b、-NR
aC(=O)NR
aR
b、-NRaC(=O)OR
b、-NR
aSO
2R
b、-OR
a、 -CN 、-C(=O)R
a、-C(=O)OR
a、-C(=O)NR
aR
b、-OC(=O)R
a、-OC(=O)OR
a、-OC(=O)NR
aR
b、-NR
aSO
2R
b、-PO
3R
a、-PO(OR
a)(OR
b) 、-SO
2R
a、-S(O)R
a、-SO(N)R
a(例如：亞碸亞胺)，-(R
a)S=NR
b(例如： 硫亞胺) 及-SR
a，其中，R
a及R
b相同或不同，且獨立地為-H、鹵代、胺基、烷基、鹵代烷基、芳基或雜環，或其中R
a及R
b與其等所連接之氮原子一起形成雜環。基於其等所連接之原子，R
a及R
b可為的複數形式。
如本說明書所用，術語「治療有效量」是指當應用於本發明的化合物時，旨在表示足以改善、減輕、穩定、逆轉、減緩或延遲病症進展或疾病狀態，或病症或疾病之症狀之化合物的量。在一實施例中，本發明的方法提供化合物組合之施用。在此種情況下，「治療有效量」是本發明化合物在組合中足以引起預期生物效應的量。
如本說明書所用，術語「治療(treatment)」或「治療(treating)」是指改善或逆轉疾病或病症進展或嚴重程度，或改善或逆轉此類疾病或病症之一種或多種症狀或副作用。如本說明書所用，「治療(treatment)」或「治療(treating)」亦意指抑制或阻斷疾病或病症之體系、症狀或狀態的進展，如延遲、阻滯、約束、妨礙或阻礙。為實現本發明之目的，「治療(treatment)」或「治療(treating)」進一步意指獲得有益或期望的臨床結果之方法，其中「有益或期望的臨床結果」包含但不限於減輕症狀、減輕疾病或疾病的程度，穩定(即不惡化)的疾病或病症狀態，疾病或病症狀態的延遲或減慢，疾病或病症狀態的改善或緩解及部分或全部疾病或病症的緩解。
化合物
本發明提供式(I)所示的化合物：
式(I)
或其藥學上可接受的鹽、水合物或溶劑化物，其中：
X是O或S；
L是鍵、-O-、-S-或-NR
6-；
R
1為烷基、環烷基、芳基、雜芳基或雜環基，其中R
1任選地被一個或多個獨立選自R
7的取代基取代；
R
6為-H或C
1-6烷基；
R
7為C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、氧代、氰基、羥基、-C(O)R
9、 -C(O)OR
9、 -C(O)NR
10R
11、-OR
9、-OC(O)R
9、-OC(O)NR
10R
11、-SR
9、 -S(O)R
9、-S(O)
2R
9、 -S(O)(=NH)R
10、-S(O)
2NR
10R
11、-NR
10R
11、-N(R
6)NR
10R
11、-N(R
6)OR
9、-N(R
6)C(O)R9、-N(R
6)C(O)OR
9、-N(R
6)C(O)NR
10R
11、-N(R
6)S(O)
2R
9、 -N(R
6)S(O)
2NR
10R
11, 或-P(O)R
12R
13；
R
9為-H、C
1-6烷基、C
1-6鹵代烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基或雜環基；
每個R
10及R
11獨立地為-H、C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基或雜環基，或R
10及R
11與其等所連接的氮原子一起形成4-到12-元雜環基，雜環基任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥烷基、-CN, -NO
2, -NR
10R
11, -NR
10C(=O)R
9,-NR
10C(=O)NR
10R11、-NR
10C(=O)OR
9、-OR
9、-C(=O)R
9、 -C(=O)OR
9、 -C(=O)NR
10R
11、 -OC(=O)R
9、-OC(=O)OR
9及 -OC(=O)NR
10R
11；
每個R
12及R
13獨立地為C
1-6烷基，C
1-6烷氧基、C
3-8環烷基、芳基、雜芳基、雜環基，或R
12及R
13與其等所連接的磷原子一起形成4-到8-元雜環基，雜環基任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥烷基、-CN、-NO
2、-NR
10R
11、-NR
10C(=O)R
9、 -NR
10C(=O)NR
10R
11、-NR
10C(=O)OR
9、-OR
9、-C(=O)R
9、-C(=O)OR
9、-C(=O)NR
10R
11、 -OC(=O)R
9、-OC(=O)OR
9及 -OC(=O)NR
10R
11；
Het選自由下列基團組成之群組：
R
a、R
b及R
c各自獨立地為-H、-D、鹵代、CF
3、CF
2H、CH
2F、CN、OR
9或NR
10R
11；
R
2為-H、-D、-CD
3、C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、羥基、-CD
2OH、-CN、-NO
2、鹵代烷基、三甲基矽烷乙氧基甲基、-C(O)R
9、-C(O)OR
9、-C(O)NR
10R
11、 -OR
9、 -OC(O)R
9、-OC(O)N R
10R
11、-SR
9、-S(O)R
9、-S(O)
2R
9、-S(O)(=NH)R
10、-S(O)
2NR
10R
11、-NR
10R
11、-N(R
6)NR
10R
11、-N(R
6)OR
9、-N(R
6)C(O)R
9、-N(R
6)C(O)R
9、-N(R
6)C(O)OR
9、-N(R
6)C(O)NR
10R
11、-N(R
6)S(O)
2R
9、-N(R
6)S(O)
2NR
10R
11或-P(O)R
12R
13，其中C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基、或雜環基可任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥烷基、-CN、-NO
2、-NR
10R
11、-NR
10C(=O)R
9、-NR
10C(=O)NR
10R
11、-NR
10C(=O)OR
9、-OR
9、-C(=O)R
9、-C(=O)OR
9、-C(=O)NR
10R
11、 -OC(=O)R
9、-OC(=O)OR
9及-OC(O=)NR
10R
11；
R
3為-H、-D、-CD
3、C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、氰基、羥基、 -CH
2OH、-CD
2OH、-OH、-CN、 -NO
2、鹵代烷基、-C(O)R
9、-C(O)OR
9、-C(O)NR
10R
11、-OR
9、-OC(O)R
9, -OC(O)NR
10R
11、-SR
9、-S(O)R
9、-S(O)
2R
9、-S(O)(=NH)R
10、-S(O
)2NR
10R
11、-NR
10R
11、-N(R
6)NR
10R
11, -N(R
6)OR
9、-N(R
6)C(O)R
9、-N(R
6)C(O)OR
9、-N(R
6)C(O)NR
10R
11、-N(R
6)S(O)
2R
9、 -N(R
6)S(O)
2NR
10R
11，或-P(O)R
12R
13；
M是鍵、-O-、-S-或-NR
6-；
R
6為-H或C
1-6烷基；
R
4為-H、-D、C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、氰基、羥基、-C(O)R
9、-C(O)OR
9、-C(O)NR
10R
11、-S(O)
2R
9、-S(O)(=NH)R
10、-S(O)
2NR
10R
11或-P(O)R
12R
13，其中C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基，或雜環基任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥烷基、-CN、-CD
3、-NO
2、-NR
10R
11、-NR
10C(=O)R
9、-NR
10C(=O)NR
10R
11、-NR
10C(=O)OR
9、-NR
10S(O)
2R
9、-OR
9、-C(=O)R
9、-C(=O)OR
9、-C(=O)NR
10R
11、-OC(=O)R
9、-OC(=O)OR
9及-OC(=O)NR
10R
11；及
R
5為-H、-D、-CD
3、C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、鹵代、羥基、-CH
2OH、-CD
2OH、-CN或鹵代烷基。
 |
在各種實施例中，L為鍵，R
1為環烷基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、鹵代、氰基、羥基、-C(O)R
9、-C(O)OR
9、-C(O)R
10R
11、-OR
9、-OC(O)R
9、-OC(O)NR
10R
11、-NR
10R
11、-N(R
6)NR
10R
11、-N(R
6)OR
9、-N(R
6)C(O)R
9、-N(R
6)C(O)OR
9及-N(R
6)C(O)NR
10R
11。
在各種實施例中，R
2及R
3中之每一個獨立地為-H、鹵代、烷基硫基、鹵代烷基或烷基。在各種實施例中，M是鍵、-O-或-NR
6-；及R
4為-H、-D、C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、氰基、羥基、-C(O)R
9、-C(O)NR
10R
11、-S(O)
2R
9、-S(O)(=NH)R
10或-S(O)
2NR
10R
11，其中，C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、芳基、雜芳基，或雜環基任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥基烷基、-CN、-CD
3、-NR
10R
11、-NR
10S(O)
2R
9及-NR
10C(=O)R
9。
 |
其中R
1、R
2、R
3、R
4、R
5、R
a、R
b、M及L如上述式(I)所定義。
在各種實施例中，L為鍵，R
1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C
1-3烷基硫基、C
1-3烷基、C
1-3羥烷基及C
1-3鹵代烷基；R
2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R
3為–H、烷基或鹵代；M是鍵、-O-、-S-或-NR
6-；R
4為–H、鹵代、烷基、羥烷基、鹵代烷基、鹵代烯基、環烷基、氰基烷基、二甲胺基、二甲胺基乙基、二甲胺基羰基、甲胺基氧乙基、胺基羰基烷基、乙醯胺基乙基、丙醯胺基乙基、甲醯胺基乙基、胺基烷基、甲胺基羰基甲基、烷氧基烷基、氮雜環丁烷基或氮雜環丁烷基甲基；R
5為–H、烷基或鹵代。
式(II)所示的非限制性示例化合物包含表1實施例1~145的化合物。在特定實施例中，該化合物選自以下組成之群組：實施例58、80、82、85、87、92、94、97、98、110、111、118、123、125、129與134之化合物。
 |
其中R
1、R
2、R
3、R
4、R
5、R
a、R
b、M及L如上述式(I)所定義。
在一些實施例中，L為鍵，R
1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C
1-3烷基、C
1-3羥烷基及C
1-3鹵代烷基；R
2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R
3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR
6-；R
4為–H、鹵代、烷基、羥烷基、二甲胺基、二甲胺基乙基、二甲胺基羰基、甲胺基氧乙基、胺基羰基烷基、乙醯胺基乙基或烷氧基烷基；R
5為–H、烷基或鹵代。
式(III)所示之非限制性示例化合物包含表1實施例146~218的化合物。在特定實施例中，化合物選自以下組成之群組：149、152、156、159、161~163、167、169、170、172~175、178、184、193、194、196、199與218之化合物。
在另一個實施例中，提供由式(IV)所示的化合物：
式(IV)。
 |
其中R
1、R
2、R
3、R
4、R
5、R
a、R
b、M及L如上述式(I)所定義。
在一些實施例中，L為鍵，R
1為環丙基，其任選地其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C
1-3烷基、C
1-3羥烷基及C
1-3鹵代烷基；R
2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R
3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR
6-；R
4為–H、鹵代、烷基、羥烷基、鹵代烷基、鹵代烯基、環烷基、氰基烷基、二甲胺基、二甲胺基乙基、二甲胺基羰基、甲胺基氧乙基、胺基羰基烷基、乙醯胺基乙基、丙醯胺基乙基、甲醯胺基乙基、環烷基烷基、環烷基(羥基)烷基、羥基環烷基、甲氧基環烷基、環烷基(甲氧基)甲基、烷氧基烷基、烯基、甲基磺醯胺基乙基、咪唑基乙基、二噁烷基、環丁基羰基胺基乙基、二氟乙醯胺基乙基、三氟乙醯胺基乙基、甲基硫代甲基、甲基硫代乙基、氮雜環丁烷基、氮雜環丁烷基甲基、環丙基羰基胺基(氰基)甲基、氰基(二氟乙醯胺基)甲基、丙基-1,1,3,3,3-d6)胺基、四氫呋喃基、甲基咪唑基乙基、呋喃基、吡咯基、甲基吡咯基、異噁唑基、四唑基烷基、甲基吡唑基或甲基吡唑基甲基；R
5為–H、烷基或鹵代。
式(IV)的非限制性示例化合物包含表1的實施例219及220的化合物。
在另一實施例中，提供一種由式(V)所示的化合物：
式(V)。
 |
其中R
1、R
2、R
3、R
4、R
5、R
a、R
b、M及L如上述式(I)所定義。
在一些實施例中，L為鍵，R
1為環烷基，其任選地其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：C
1-6烷基、C
2-6烯基、C
2-6炔基、環烷基、鹵代、氰基、羥基、-C(O)R
9、-C(O)OR
9、-C(O)NR
10R
11、-OR
9、-OC(O)R
9、-OC(O)NR
10R
11、-NR
10R
11、-N(R
6)NR
10R
11、-N(R
6)OR
9、-N(R
6)C(O)R
9、-N(R
6)C(O)OR
9及-N(R
6)C(O)NR
10R
11。在一些其他實施例中，R
1為環烷基，其任選地其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C
1-3烷基、C
1-3羥烷基及C
1-3鹵代烷基。
式(V)所示的非限制性示例化合物包含表1實施例221~445的化合物。
在一些實施例中，R
1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C
1-C
3烷基、C
1-C
3羥烷基及C
1-C
3鹵代烷基；R
2為–H、烷基、烷基硫基、鹵代烷基或鹵代；R
3為–H、烷基或鹵代；M為鍵、-O-或-NR
6-；R
4為–H、鹵代、烷基、單烷基胺基或二烷基胺基；R
5為–H、烷基或鹵代。非限制性示例化合物包含以下一種：
(1S,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；
(1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；
(1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；
(1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-(三氟甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；
(1S,2S)-N-(6-(5-氯-6-氟-7-(異丙基胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；及
(1S,2S)-N-(6-(5-氯-6-氟-7-異丙基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺。
在一些實施例中，R
1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C
1-3烷基、C
1-3羥烷基及C
1-3鹵代烷基；R
2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R
3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR
6-；R
4為–H、鹵代、烷基、羥烷基、鹵代烷基、鹵代烯基、環烷基、單烷基胺基或二烷基胺基；及R
5為–H、烷基或鹵代。非限制性示例化合物包含一種化合物，該化合物選自以下組成之群組：實施例258、261、265、266、269、272、275、280、288、291、293、296、297、300、304、306、310、318、320、324、327、329、330、332、334、336、341、345、349、353、356、358、359、361、366、371、372、374、390、391、393、404、405、408、410、414、417、419、422、423、425、426、428、430、433、434、436、439、441及445。
在一些實施例中，R
1為環丙基，其任選地被選自鹵代、C
1-3烷基、C
1-3羥烷基和C
1-3鹵代烷基的一個或多個基團取代；R
2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R
3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR
6-；R
4為–H、鹵代、烷基、烷基羰基、二烷基胺基碳基、氧吡咯烷基、羥基烷基、鹵代烷基、鹵代烯基、環烷基、吡啶基、單烷基胺基或二烷基胺基；R
5為–H、烷基或鹵代。非限制性示例化合物包含一種化合物，該化合物選自以下組成之群組：實施例258、261、265、266、268、269、271~273 275、280、281、288、290、291、293、296~298、300、304、306、307、310、316、318、320、324、326、327、329、330~334、336、339、341、345、346、349、353、356、358、359、361~363、365~367、370~ 374、377~379、383、388、390、391、393、398、401、404~ 406、408~410、414、415、417、419、421~426、428、430、433、434、436、439、441及445。
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其中R
1、R
2、R
3、R
4、R
5、R
a、R
b、M及L如上述式(I)所定義。
在一些實施例中，L為鍵，R
1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C
1-3烷基、C
1-3羥烷基及C
1-3鹵代烷基；R
2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R
3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR
6-；R
4為–H、鹵代、烷基、羥烷基、鹵代烷基、鹵代烷基醯胺基烷基、鹵代烷基羰基胺基烷基、烷基胺基烷基、羥基鹵代烷基、鹵代烯基、環烷基、氰基、氰基烷基、二甲胺基、二甲胺基乙基、甲胺基羰基、二甲胺基羰基、甲胺基氧乙基、胺基羰基烷基、乙醯胺基乙基、二烷基胺基環烷基，胺基環烷基、甲胺基環烷基、環烷基烷基、環烷基(羥基)烷基、環烷基醯胺烷基、環烷基胺基羰基、羥基環烷基、甲氧基環烷基、環烷基(甲氧基)甲基、烷氧基羰基、烷基羰基、烷基醯胺烷基、烷氧基烷基、烯基、甲基磺醯胺基乙基、咪唑基乙基、二噁烷基、氮雜環丁烷基、氮雜環丁烷基甲基、四氫呋喃基、呋喃基、嘧啶基、吡啶基、吡咯基、鹵代吡咯烷基、吡咯烷基、甲基吡咯基、異噁唑基、四唑烷基、三嗪基、甲基吡唑基或甲基吡唑基甲基；R
5為–H、烷基或鹵代。
(VI)所示的非限制性示例化合物包含表1實施例446~666之化合物。在特定實施例中，該化合物選自選自以下組成之群組：實施例464、466、467、476、477、480、484、485、487、488、490~494、496、497、502~505、509、513、514、519~521、523~525、529~532、534、541、543、548、550、552、556~558、561~565、568~574、577、579、581、585、586、588、592、596~600、602、607、612、615、617~619、621、623、625、629、634、636~642、644、646、650~652、655~657及659~665。
在一個實施例中，提供一種藥物組成物，其包含藥學上可接受的載體或稀釋劑及式(I)所示化合物或其藥學上可接受的鹽。
化合物的醫療用途以及使用該化合物進行治療之方法
本發明提供一種治療患有與HPK1調節相關疾病或病症的受試者之方法，該方法包含：向有需要的受試者施用治療有效量之式1化合物或其藥學上可接受的鹽。在一些實施例中，與HPK1調節相關疾病或病症是癌症、轉移、炎症或包含自體免疫疾病之免疫疾病。
在一些其他實施例中，該疾病為癌症、轉移、炎症或自體免疫疾病。在特定實施例中，該癌症選自下列組成之群組：腫瘤癌、黑色素瘤、胚細胞瘤、肉瘤、淋巴瘤及白血病，包含但不限於膀胱癌、腦瘤、乳腺癌、子宮頸癌、大腸直腸癌、食道癌、子宮內膜癌、肝細胞癌、喉癌、肺癌、骨肉瘤、卵巢癌、胰腺癌、前列腺癌、腎癌和甲狀腺癌、急性淋巴球白血病、急性骨髓性白血病、室管膜瘤、尤文氏肉瘤、神經膠母細胞瘤、髓母細胞瘤、 神經胚細胞瘤、橫紋肌肉瘤、橫紋肌樣癌及腎胚細胞瘤(威爾姆氏腫瘤)。
在一些實施例中，自體免疫疾病是發炎性腸道疾病、艾迪森氏病、斑禿、僵直性脊柱炎、抗磷脂質症候群、溶血性貧血、自身免疫性肝炎、貝西氏症、柏格氏病、大疱性類天疱瘡、心肌病、乳糜瀉、慢性疲勞免疫功能障礙綜合症(CFIDS)、慢性發炎脫髓鞘性多發神經病變、Churg-Strauss症候群、瘢痕性類天疱瘡、冷凝集素病、第1型糖尿病、盤狀狼瘡、原發性冷凝球蛋白症、葛瑞夫兹氏病、格林─巴利症候群、橋本氏甲狀腺炎、甲狀腺低能症、自體免疫性淋巴增生綜合症(ALPS)、特發性肺纖維化、特發性血小板減少性紫斑症(ITP)、幼年關節炎、扁平苔蘚、紅斑性狼瘡、梅尼爾氏症、混合結締組織病、多發性硬化、重症肌無力、尋常型天疱瘡、惡性貧血、多發性軟骨炎、自體免疫多腺症、風濕性多發性肌痛症、多發性肌炎、皮肌炎、原發性無γ球蛋白血症、原發性膽汁性肝硬化、牛皮癬、牛皮癬性關節炎、 Raynaud氏現象、Reiter氏症候群、風濕熱、類風濕性關節炎、類肉瘤病、硬皮病、乾燥症候群、僵硬人症候群、高安氏動脈炎、巨細胞動脈炎、潰瘍性結腸炎、眼色素層炎、血管炎或肉芽腫伴多血管炎。
在另一實施例中，提供式(I)所示的化合物或其藥學上可接受的鹽，以製備藥物用於抑制需要抑制HPK1活性的受試者的HPK1活性。在一些實施例中，該用途包含治療癌症或自體免疫疾病。
根據本發明的待治療的合適受試者包含哺乳動物受試者。根據本發明的哺乳動物包含但不限於人、犬、貓、牛、山羊、馬、綿羊、豬、齧齒動物、兔類、靈長類等，且包含子宮內的哺乳動物。受試者可是任何性別，也可處於任何發育階段。在一實施例中，根據本發明的待治療的合適受試者是人。
本發明的化合物通常以治療有效量施用。本發明的化合物可藉由任何適合的途徑以適於該途徑之藥物組成物的形式，且以對於預期治療有效的劑量施用。有效劑量通常在約0.01~約1000mg/kg體重/天之範圍內，理想為約0.01~約500mg/kg/天，以單次或分次劑量。根據年齡、物種及所治療的疾病或病症，低於該範圍下限的劑量水平可能是合適的。在其他情況下，可使用更大的劑量而無有害副作用。較大的劑量亦可分成幾個較小的劑量，用於全天施用。確定合適劑量的方法在本發明所屬的技術領域中是習知的。例如：可使用Remington： The Science and Practice of Pharmacy, Mack Publishing Co., 20th ed., 2000。
藥物組成物、劑型及給藥途徑
為治療上述提及之疾病或病症，本發明所述之化合物或其藥學上可接受的鹽可以方式施用：
口服給藥
本發明的化合物可口服給藥，包含藉由吞咽，使得化合物進入胃腸道，或直接從口腔吸收到血流中(例如：口頰或舌下給藥)。適合口服給藥的組成物包含固體、液體、凝膠或粉末製劑，並具有諸如片劑、口含錠、膠囊、顆粒劑或粉末的劑型。用於口服給藥的組成物可配製成立即釋放或修飾釋放，包含延遲釋放或緩釋，任選地帶有腸溶衣。液體製劑可包含溶液、糖漿及懸浮液，其可用於軟膠囊或硬膠囊。此種製劑可包含藥學上可接受的載體，例如水、乙醇、聚乙二醇、纖維素或油。製劑還可包含一種或多種乳化劑及/或懸浮劑。
在片劑劑型中，按劑型的重量計，存在之藥物量可為重量的約0.05%至約95%，更通常為約2%至約50%。另外，片劑可含有崩散劑，按重量計，含有約0.5%至約35%，更通常為劑型的約2%至約25%。崩散劑之實例包含但不限於乳糖、澱粉、羥基乙酸澱粉鈉、交聯聚維酮(crospovidone)、交聯羧甲基纖維素鈉(croscarmellose sodium)、麥芽糖糊精或其混合物。
用於片劑合適的潤滑劑，按重量計，可為約0.1%至約5%，且包但不限於滑石、二氧化矽、硬脂酸、硬脂酸鈣、硬脂酸鋅或硬脂酸鎂、反丁醯二酸硬脂酸鈉等。
用於片劑合適的黏合劑包含但不限於明膠、聚乙二醇、糖、樹膠、澱粉、聚乙烯吡咯烷酮、羥丙基纖維素、羥丙基甲基纖維素等。用於片劑合適的稀釋劑包含但不限於甘露醇、木糖醇、乳糖、右旋糖、蔗糖、山梨糖醇、微晶纖維素及澱粉。
用於片劑的合適增溶劑，按重量計，可為約0.1%至約3%，且包含但不限於聚山梨糖醇酯、硫酸月桂酯鈉、十二烷基硫酸鈉、碳酸丙烯酯、二甘醇單乙醚、二甲基異山梨醇、蓖麻油聚乙二醇(天然或氫化)、HCOR
TM(Nikkol)、油基酯、Gelucire
TM、辛酸/辛酸單/雙甘油酯、山梨醇酐脂肪酸酯及Solutol HS
TM。
注射給藥
本發明的化合物可直接給藥到血流、肌肉或內部器官中。注射給藥的合適方式包含靜脈內、肌肉內、皮下動脈內、腹膜內、鞘內腔、顱內等。注射給藥的合適裝置包含注射器(包含針式及無針式注射器)及輸注方法。
用於注射給藥之組成物可配製成立即釋放或修飾釋放，包含延遲釋放或緩釋。大多數注射製劑是含有賦形劑之水溶液，包含鹽類、緩衝劑及等張劑。注射製劑亦可以脫水形式(例如：藉由凍乾)或作為無菌非水溶液製備。此等製劑可與合適的載體一起使用，諸如無菌水。溶解度增強劑亦可用於製備注射溶液。
經皮給藥
本發明的化合物可局部給藥至皮膚或經皮給藥。用於此種局部給藥之製劑可包含乳液、溶液、乳膏、凝膠、水凝膠、軟膏、泡沫、植入物、貼片等。用於局部給藥製劑之藥學上可接受的載體可包含水、乙醇、礦物油、甘油、聚乙二醇等。局部或經皮給藥亦可藉由電穿孔、離子電滲療法、聲滲療法等進行。用於局部給藥之組成物可配製成立即釋放或修飾釋放，包含延遲釋放或緩釋。
聯合療法
根據本發明之藥物組成物可含有一種或多種附加治療劑，例如：以增加療效或減少副作用。因此，在一些實施例中，藥物組成物進一步含有一種或多種附加治療劑，附加治療劑選自用於治療或抑制由HPK1直接或間接介導的疾病之活性成分。此種活性成分之實例是但不限於治療癌症、轉移、炎症或自體免疫發病機制之藥劑。在一些實施例中，式(I)化合物與抗PD-1劑、抗PD-L1劑或抗CTLA4劑一起施用。
製備藥物組成物之參考文獻
製備用於治療或預防疾病或病症的藥物組成物之方法是本發明所屬技術領域中習知的。例如：根據Handbook of Pharmaceutical Excipients (7
thed.)、Remington: The Science and Practice of Pharmacy (20
thed.)、Encyclopedia of Pharmaceutical Technology (3
rded.)或Sustained and Controlled Release Drug Delivery Systems (1978)，可選擇藥學上可接受的賦形劑、載體、添加劑等，從而與本發明的化合物混合用於製成藥物組成物。
本發明提供透過抑制HPK1活性而具有多種藥理作用之化合物、具有該化合物作為有效藥劑的藥物組成物、該化合物之醫療用途，特別是用於治療由HPK1調節的疾病或病症，及治療或預防方法，包含向需要此種治療或預防之受試者施用該化合物。本發明之化合物及其藥學上可接受的鹽具有良好的安全性及對HPK1的高選擇性，因此表現出其作為藥物的優異性質。
化合物製備
以下製備實施例說明可用於製備式(I)化合物之中間化合物的製備。本發明新型中間化合物及用於製備中間化合物的合成方法代表本發明的實施方式。
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步驟1)3-溴-4-氯-5-氟-2-甲基苯胺
向3-溴-5-氟-2-甲基苯胺(50g，245mmol，1eq)的AcOH(100mL)溶液中加入N-氯琥珀醯亞胺(36g，270mmol，1.1eq)。將混合物在25℃下攪拌16小時。在真空下濃縮混合物並用二氯甲烷(200mL*2)萃取殘餘物。將合併的有機層用飽和NaHCO
3200 mL洗滌，經Na
2SO
4乾燥，過濾並在減壓下濃縮以得到殘餘物。獲得呈黑色油狀之粗產物(66g，粗品)。
步驟2)4-溴-5-氯-6-氟-1H-吲唑
向3-溴-4-氯-5-氟-2-甲基苯胺(25.8g，108mmol，1eq)的AcOH(1.96L，0.05M)、H
2O(0.065L，1.5M)溶液中加入亞硝酸鈉(8.96g，130mmol，1.2eq)。將混合物在25℃下攪拌16小時。在真空下濃縮混合物並用二氯甲烷(1L*2)萃取殘餘物。將合併的有機層用飽和NaHCO
3(1L)洗滌，經Na
2SO
4乾燥，過濾並在減壓下濃縮以得到殘餘物。獲得呈棕色固體的粗產物(23.6g，粗品)。
步驟3)4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑
向4-溴-5-氯-6-氟-1H-吲唑(1.98g，7.97mmol，1eq)的THP(40mL)溶液中加入3,4-二氫-2H-哌喃(2.18ml，23.9mmol，3eq)及對甲苯磺酸單水合物(300mg，1.59mmol，0.2eq)。將反應混合物在70℃下攪拌14小時。用乙酸乙酯萃取反應混合物並經MgSO
4乾燥。有機殘餘物透過管柱層析法(矽膠，己烷:乙酸乙酯=1:0至4:1)純化。獲得4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑(1.51g，4.54mmol，57%產率)。
1H NMR (400MHz, DMSO-d
6) δ 8.16 (s, 1H), 8.00 (dd, J = 9.3, 1.1 Hz, 1H), 5.85 (dd, J = 9.6, 2.5 Hz, 1H), 3.87 (d, J = 12.6 Hz, 1H), 3.79-3.72 (m, 1H), 2.38-2.30 (m, 1H), 2.04-1.94 (m, 2H), 1.77-1.55 (m, 3H).
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步驟1)4-溴-5-氯-6-氟-7-碘-1H-吲唑
向4-溴-5-氯-6-氟-1H-吲唑(2g，8.02mmol)的硫酸(1.7mL)溶液中分批加入N-碘琥珀醯亞胺(2.7g，12.03mmol)。將混合物在0℃下攪拌3小時。反應完成後，將混合物倒入冰水中，並用固體NaOH驟冷，再用二氯甲烷萃取。在真空下濃縮合併之有機殘餘物。(2.99g，粗品)。
1H NMR (400MHz, DMSO-d
6) δ 13.91 (s, 1H), 8.27 (d, J = 1.6 Hz, 1H)。
步驟2)4-溴-5-氯-6-氟-7-碘-2-(四氫-2H-哌喃-2-基)-2H-吲唑
向4-溴-5-氯-6-氟-7-碘-1H-吲唑(2.99g，7.97mmol，1eq)的THP(40mL)溶液中加入3,4-二氫-2H-哌喃(2.18ml，23.9mmol，3eq)及對甲苯磺酸單水合物(300mg，1.59mmol，0.2eq)。將反應混合物在60℃下攪拌16小時。用乙酸乙酯萃取反應混合物並經MgSO
4乾燥。將有機殘餘物透過管柱層析法(矽膠，己烷:乙酸乙酯=1:0~4:1)純化。獲得4-溴-5-氯-6-氟-7-碘-2-(四氫-2H-哌喃-2-基)-2H-吲唑(1.64g、7.97mmol、60.7％產率)。
1H NMR (400MHz, DMSO-d
6) δ 8.84 (s, 1H), 5.80 (dd, J = 9.9, 2.7 Hz, 1H), 5.66 (s, 1H), 4.02 (t, J = 6.6 Hz, 1H), 3.85-3.70 (m, 1H), 2.33-2.21 (m, 1H), 2.08-1.91 (m, 2H), 1.79-1.45 (m, 4H)。
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步驟1)4-溴-5-氯-6-氟-7-硝基-1H-吲唑
向在0℃下攪拌的HNO
3(12.63g，200.43mmol，9.02mL，5eq)的H
2SO
4(50mL)混合物中緩慢加入4-溴-5-氯-6-氟-1H-吲唑(10g，40.09mmol，1eq)。加入後將混合物在0℃下攪拌2小時。TLC(石油醚：乙酸乙酯=3:1)顯示所有反應物都被消耗，並出現一個主要的新點。將混合物倒入冰水中，用乙酸乙酯(50mL*3)萃取，合併的有機相經Na
2SO
4乾燥，過濾並濃縮濾液獲得呈黃色固體的4-溴-5-氯-6-氟-7-硝基-1H-吲唑(12g，粗品)。
步驟2)4-溴-5-氯-6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-2H-吲唑
向4-溴-5-氯-6-氟-7-硝基-1H-吲唑(2.34g，7.97mmol，1eq)的THF(40mL)溶液中加入3,4-二氫-2H-哌喃(2.18ml，23.9mmol，3eq)和對甲苯磺酸單水合物(300mg，1.59mmol，0.2eq)。將反應混合物在60℃下攪拌14小時。用乙酸乙酯萃取反應混合物並經MgSO
4乾燥。有機殘餘物透過管柱層析法(矽膠，己烷:乙酸乙酯=1:0-4:1)純化。獲得4-溴-5-氯-6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-2H-吲唑(1.65g，4.35mmol，54.7％產率)。
步驟3)4-溴-5-氯-6-氟-2-(四氫-2H-哌喃-2-基)-2H-吲唑-7-胺
向4-溴-5-氯-6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-2H-吲唑(600mg，1.58mmol，1eq)的EtOH(5mL)與H
2O(5mL)溶液中加入NH
4Cl(508.66mg，9.51mmol，6eq)和Fe(531.04mg，9.51mmol，6eq)，接著將反應混合物在80℃下攪拌1小時。過濾反應混合物，用乙酸乙酯(20mL)稀釋濾液，用水(20mL*2)洗滌混合物，接著有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過prep-TLC(SiO
2，石油醚/乙酸乙酯＝1:1)純化殘餘物。獲得呈黃色油狀的4-溴-5-氯-6-氟-2-(四氫-2H-哌喃-2-基)-2H-吲唑-7-胺(390mg、1.12mmol、70.59%產率)。
1H NMR (400MHz, DMSO-d
6) δ 8.41 (s, 1H), 5.85 (br s, 2H), 5.71 (br d, J=8.0 Hz, 1H), 4.00 (br d, J=11.3 Hz, 1H), 3.77 - 3.59 (m, 1H), 2.29 - 2.17 (m, 1H), 2.10 - 1.91 (m, 2H), 1.78 - 1.54 (m, 3H)。
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步驟1)4-溴-5-氯-6-氟-7-硝基-1H-吲唑
在-15℃下向中間物1A(900mg，3.61mmol，1eq)的H
2SO
4(10mL)(98%純度)溶液中逐滴加入HNO
3(419.69mg，4.33mmol，299.78uL，1.2eq)(65%純度)，接著將反應混合物在0℃下攪拌2小時。將反應混合物緩慢倒入冰水(20mL)中，接著用飽和NaOH水溶液將混合物的pH值調節至pH=7，接著用乙酸乙酯(30mL*2)萃取混合物，合併的有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。獲得呈黃色固體的4-溴-5-氯-6-氟-7-硝基-1H-吲唑(900mg，粗品)。
1H NMR (400MHz, DMSO-d
6) δ 14.36 (br s, 1H), 8.37 (br s, 1H)。
步驟2)4-溴-5-氯-6-氟-7-硝基-1-(四氫-2H-哌喃-2-基)-1H-吲唑
向4-溴-5-氯-6-氟-7-硝基-1H-吲唑(900mg，3.06mmol，1eq)(粗品)的DCM(10mL)溶液中加入TsOH.H
2O(58.14mg，305.64umol，0.1eq)和DHP(771.27mg，9.17mmol，838.34uL，3eq)，接著將反應混合物在20℃下攪拌2小時。用二氯甲烷(20mL)稀釋反應混合物，並用NaHCO
3(15mL*2)的飽和水溶液洗滌混合物，有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。殘餘物透過管柱層析法純化(SiO
2，石油醚/乙酸乙酯=40/1~25:1，4-溴-5-氯-6-氟-7-硝基-1-(四氫-2H-哌喃-2-基)-1H-吲唑在石油醚/乙酸乙酯=40/1時出現，4-溴-5-氯-6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-2H-吲唑在石油醚/乙酸乙酯=25/1時出現)。獲得呈棕色固體的4-溴-5-氯-6-氟-7-硝基-1-(四氫-2H-哌喃-2-基)-1H-吲唑(200mg，528.29umol，17.28%產率)。獲得呈黃色固體的4-溴-5-氯-6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-2H-吲唑(600mg，1.58mmol，51.85%產率)。
4-溴-5-氯-6-氟-7-硝基-1-(四氫-2H-哌喃-2-基)-1H-吲唑
1H NMR (400MHz, DMSO-d
6) δ 8.43 (s, 1H), 5.50 (dd, J=2.8, 7.8 Hz, 1H), 3.45 - 3.38 (m, 2H), 2.35 - 2.27 (m, 1H), 2.23 - 2.14 (m, 1H), 1.92 (td, J=4.6, 13.6 Hz, 1H), 1.68 (ddt, J=4.0, 10.1, 13.9 Hz, 1H), 1.59 - 1.36 (m, 2H)。
4-溴-5-氯-6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-2H-吲唑
1H NMR (400MHz, DMSO-d
6) δ 8.99 (s, 1H), 5.86 (dd, J=2.7, 9.7 Hz, 1H), 4.08 - 3.96 (m, 1H), 3.81 - 3.68 (m, 1H), 2.28 - 2.14 (m, 1H), 2.14 - 2.02 (m, 1H), 2.02 - 1.89 (m, 1H), 1.78 - 1.67 (m, 1H), 1.64 - 1.56 (m, 2H)。
步驟3)4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-胺
向4-溴-5-氯-6-氟-7-硝基-1-(四氫-2H-哌喃-2-基)-1H-吲唑(200mg，528.29umol，1eq)的EtOH(5mL)和H
2O(5mL)的溶液中加入NH
4Cl(169.55mg，3.17mmol，6eq)和Fe(177.03mg，3.17mmol，6eq)，接著將反應混合物在80℃下攪拌2小時。過濾反應混合物，並將濾液濃縮以除去EtOH，接著用乙酸乙酯(20mL)稀釋混合物，用水(20mL*2)洗滌混合物，接著有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。獲得呈黃色固體的4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-胺(140mg，粗品)。
步驟4)4-溴-5-氯-6-氟-N,N-二甲基-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-胺
在0℃下於N
2中向4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-胺(120mg，344.24umol，1eq)的THF(5mL)溶液中分批加入NaH(34.42mg，860.59umol，60%純度，2.5eq)，接著將混合物在0℃下於N
2中攪拌30分鐘，接著逐滴加入MeI(293.16mg，2.06mmol，128.58uL，6eq)，並將反應混合物在20℃下於N
2中攪拌12小時。將反應混合物倒入NH
4Cl的飽和水溶液(20mL)中，接著用乙酸乙酯(20mL*2)萃取混合物，合併的有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過prep-TLC(SiO
2，石油醚/乙酸乙酯＝5:1)純化殘餘物。獲得呈黃色油狀的中間物1E(30mg，78.06umol，22.68%產率，98%純度)。
中間物1E。4-溴-5-氯-6-氟-N-異丙基-2-(四氫-2H-哌喃-2-基)-2H-
吲唑-7-胺
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向中間物1B(100mg，0.218mmol，1eq)的2-甲基-2-丁醇(1.09mL)溶液中加入Xantphos Pd G3(21mg，21.8μmol，0.1eq)及Cs
2CO
3(142mg，0.436mmol，2.0eq)。將混合物脫氣並用N
2氣沖3次，接著加入丙-2-胺(0.19mL，2.18mmol，10eq)。將混合物在密封管中於90℃下攪拌3小時。用H
2O(40mL)稀釋反應混合物，接著用DCM(50mL*3)萃取混合物。合併的有機層經Na
2SO
4乾燥，過濾並在真空下濃縮濾液以得到殘餘物。透過矽膠層析法純化殘餘物(產物在己烷/乙酸乙酯＝10/1時出現)以提供呈米色固體的中間物1E(47mg，0.120mmol，55%產率)。
1H NMR (400 MHz, DMSO-d
6) δ 8.43 (s, 1H), 5.74 (dd, J = 9.6, 2.5 Hz, 1H), 5.29 (dd, J = 9.9, 3.3 Hz, 1H), 4.63-4.57 (m, 1H), 3.99 (d, J = 11.0 Hz, 1H), 3.74-3.68 (m, 1H), 2.23-2.17 (m, 1H), 2.05-1.95 (m, 2H), 1.74-1.57 (m, 3H), 1.23-1.18 (m, 6H)。
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向中間物1E(600mg，1.54mmol，1.0eq)的甲醇(7.7mL)溶液中加入甲醛(0.572mL，7.68mmol，5.0eq)和乙酸(88μL，1.54mmol，1.0eq)。混合物在室溫下攪拌10分鐘。加入氰基硼氫化鈉(290mg，4.61mmol，3.0eq)，接著將混合物在室溫下攪拌16小時。用H
2O驟冷反應混合物並用乙酸乙酯(150mL*3)萃取。合併的有機層經Na
2SO
4乾燥，過濾並在真空下濃縮濾液以得到殘餘物。透過矽膠層析法純化殘餘物(產物在己烷/乙酸乙酯＝100/4時出現)以提供呈棕色油狀的中間物1F(292mg，0.722mmol，47%產率)。
1H NMR (400 MHz, DMSO-d
6) δ 8.51 (s, 1H), 5.75 (dd, J = 9.3, 2.7 Hz, 1H), 4.14-4.05 (m, 1H), 4.00-3.93 (m, 1H), 3.78-3.67 (m, 1H), 2.92 (d, J = 4.4 Hz, 3H), 2.23-2.20 (m, 1H), 2.05-1.95 (m, 2H), 1.75-1.60 (m, 3H), 1.17 (d, J = 6.6 Hz, 6H)。
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步驟1)4-溴-5-氯-6-氟-1H-吲唑-7-胺
向4-溴-5-氯-6-氟-7-硝基-1H-吲唑(12g，40.75mmol，1eq)的EtOH(100mL)和H
2O(40mL)的溶液中加入Fe(6.83g，122.26mmol，3eq)及NH
4Cl(6.54g，122.26mmol，3eq)。將反應混合物加熱至80℃並反應2小時。透過矽藻土濾餅過濾反應混合物，濃縮濾液以得到粗產物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯＝20/1至3/1)純化殘餘物。獲得呈黃色固體的4-溴-5-氯-6-氟-1H-吲唑-7-胺(5g，18.90mmol，46.39%產率)。
步驟2)N-(4-溴-5-氯-6-氟-1H-吲唑-7-基)乙醯胺
向4-溴-5-氯-6-氟-1H-吲唑-7-胺(3g，11.34mmol，1eq)的AcOH(30mL)溶液中加入Ac
2O(1.39g，13.61mmol，1.27mL，1.2eq)，將反應混合物加熱至80℃並反應3小時。在真空下除去溶劑。殘餘物透過管柱層析法(SiO
2，石油醚/乙酸乙酯=50/1至4/1)純化以獲得呈黃色固體的N-(4-溴-5-氯-6-氟-1H-吲唑-7-基)乙醯胺(3g，9.79mmol，86.29%產率)。
步驟3)4-溴-5-氯-N-乙基-6-氟-1H-吲唑-7-胺
在0℃下於N
2中向LAH(520.00mg，13.70mmol，1.5eq)的THF(50mL)溶液中逐滴加入N-(4-溴-5-氯-6-氟-1H-吲唑-7-基)乙醯胺(2.8g，9.13mmol，1eq)的THF(100mL)溶液，加入後，使反應混合物升溫至25℃，並反應16小時。將混合物倒入水(500mL)中，用乙酸乙酯(100mL*2)萃取，合併的有機相經Na
2SO
4乾燥，過濾並濃縮濾液以得到粗品。殘餘物透過管柱層析法(SiO
2，石油醚/乙酸乙酯=50/1至2/1)純化以獲得呈黃色固體的4-溴-5-氯-N-乙基-6-氟-1H-吲唑-7-胺(1g，3.42mmol，37.42%產率)。
步驟4)4-溴-5-氯-N-乙基-6-氟-N-甲基-1H-吲唑-7-胺
向4-溴-5-氯-N-乙基-6-氟-1H-吲唑-7-胺(1.4g，4.79mmol，1eq)和 HCHO(718.48mg，23.93mmol，659.16uL，5eq)的MeOH(50mL)溶液中加入NaBH
3CN(902.21mg，14.36mmol，3eq)和AcOH(287.38mg，4.79mmol，273.70uL，1eq)。將反應混合物在25℃下攪拌16小時。在真空下除去溶劑。殘餘物透過管柱層析法(SiO
2，石油醚/乙酸乙酯=50/1至5/1)純化以獲得呈白色固體的4-溴-5-氯-N-乙基-6-氟-N-甲基-1H-吲唑-7-胺(1.4g，4.57mmol，95.42%產率)。
中間物1H。4-溴-5-氯-6-氟-7-甲基-1-(四氫-2H-哌喃-2-基)-1H-吲唑
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步驟1)4-溴-6-氟-7-硝基-1H-吲唑
在0℃下向4-溴-6-氟-1H-吲唑(10g，46.51mmol，1eq)的H
2SO
4(80mL)(98%純度)溶液中分批加入KNO
3(4.70g，46.51mmol，1eq)，接著在0℃下將混合物攪拌1小時。接著將反應混合物倒入冰水(200mL)中，並用乙酸乙酯(100mL*2)萃取混合物，合併的有機層用飽和NaHCO
3水溶液(100mL*2)和鹽水(100mL)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。殘餘物經矽膠層析法純化(200~300篩孔矽膠，石油醚/乙酸乙酯=15/1至1/1，產物4-溴-6-氟-7-硝基-1H-吲唑在石油醚/乙酸乙酯=8/1時出現)，以得到呈黃色固體的 4-溴-6-氟-7-硝基-1H-吲唑 (2.7g，10.38mmol，22.32%產率)和粗產物。透過MPLC(石油醚/乙酸乙酯)純化粗產物，以得到呈黃色固體的4-溴-6-氟-7-硝基-1H-吲唑(3.57g，13.73mmol，29.52%產率)。
步驟2)4-溴-6-氟-5-碘-7-硝基-1H-吲唑
在25℃下向4-溴-6-氟-7-硝基-1H-吲唑(2.7g，10.38mmol，1eq)的H
2SO
4(30mL)溶液中加入 NIS(7.01g，31.15mmol，3eq)。將反應混合物在50℃下攪拌16小時。用冰水(50mL)驟冷反應混合物。接著用乙酸乙酯(50mL*3)萃取混合物。合併的有機層用Na
2SO
3水溶液(20mL*2)、NaHCO
3水溶液(20mL*2)及鹽水(20mL)洗滌，經硫酸鈉乾燥，過濾並在真空下濃縮濾液以得到呈黃色固體的4-溴-6-氟-5-碘-7-硝基-1H-吲唑(3.4g，8.81mmol，84.85%產率)。
1H NMR (400 MHz, DMSO-d
6) δ 14.28 (br s, 1H), 8.30 (s, 1H)。
步驟3)4-溴-6-氟-5-碘-1H-吲唑-7-胺
向4-溴-6-氟-5-碘-7-硝基-1H-吲唑(3.4g，8.81mmol，1eq)的EtOH(50mL)及H
2O(25mL)溶液中加入NH
4Cl(2.83g，52.86mmol，6eq)，接著在60℃下分批加入Fe(2.95g，52.86mmol，6eq)。將混合物在80℃下攪拌1小時。反應混合物趁熱透過矽藻土過濾。接著在真空下濃縮濾液以除去EtOH。用乙酸乙酯(50mL*2)萃取所得水相。合併的有機層用鹽水(50mL)洗滌，經硫酸鈉乾燥，過濾並在真空下濃縮濾液，以得到殘餘物。殘餘物經矽膠層析法純化(MPLC，石油醚/乙酸乙酯=5/1至2/1，產物在石油醚/乙酸乙酯=2/1時出現)，以得到呈灰色固體的4-溴-6-氟-5-碘-1H-吲唑-7-胺(2.2g，6.18mmol，70.16%產率)。
1H NMR (400 MHz, DMSO-d
6) δ 13.09 (br s, 1H), 7.86 (d, J = 1.7 Hz, 1H), 5.62 (s, 2H)。
步驟4)4-溴-6-氟-5-碘-N,N-二甲基-1H-吲唑-7-胺
向4-溴-6-氟-5-碘-1H-吲唑-7-胺(2.2g，6.18mmol，1eq)的MeOH(50mL)溶液中加入 AcOH(1.11g，18.54mmol，1.06mL，3eq)及HCHO(5.02g，61.81mmol，4.60mL，10eq)，接著在40℃下分批加入NaBH
3CN(3.88g，61.81mmol，10eq)。氣體釋放且溫度升高。懸浮液在25℃下攪拌16小時。將反應混合物倒入水(50mL)中，接著將混合物濃縮以除去MeOH，用乙酸乙酯(50mL*2)萃取混合物，並將合併的有機層用鹽水(50mL)洗滌，經硫酸鈉乾燥，過濾並減壓濃縮以得到殘餘物。殘餘物經矽膠層析法純化(200~300d 篩孔矽膠，石油醚/乙酸乙酯=15/1至8/1，產物在石油醚/乙酸乙酯=8/1時出現)，以得到呈灰白色固體的4-溴-6-氟-5-碘-N,N-二甲基-1H-吲唑-7-胺(2.05g，5.34mmol，86.37%產率)。
步驟5) 4-溴-6-氟-N,N-二甲基-5-(甲硫基)-1H-吲唑-7-胺
向配備磁力攪拌棒的100mL瓶中依次加入4-溴-6-氟-5-碘-N,N-二甲基-1H-吲唑-7-胺 (1.2g，3.13mmol，1eq)，NaSMe(328.56mg，4.69mmol，1.5eq)，Xantphos(361.65mg，625.02umol，0.2eq)，K
2CO
3(1.30g，9.38mmol，3eq)，二噁烷(20mL)和Pd
2(dba)
3(286.17mg，312.51umol，0.1eq)。將瓶子抽真空並用氮氣回填。接著將混合物於氮環境中在90℃下攪拌16小時。殘餘物經矽膠層析法純化(200~300篩孔矽膠，石油醚/乙酸乙酯=20/1至8/1，產物在石油醚/乙酸乙酯=10/1時出現)，以得到呈橙色固體的4-溴-6-氟-N,N-二甲基-5-(甲硫基)-1H-吲唑-7-胺(540mg，1.78mmol，56.81%產率)。
1H NMR (400 MHz, DMSO-d
6) δ 13.59 (br s, 1H), 8.00 (d, J = 1.6 Hz, 1H), 2.91 (d, J = 2.4 Hz, 6H), 2.39 (s, 3H)。
 |
向4-溴-6-氟-5-碘-N,N-二甲基-1H-吲唑-7-胺(1.0g，2.61mmol，1eq)及2,2-二氟-2-(氟磺醯基)乙酸甲酯(1.00g，5.22mmol，664.45uL，2eq)的DMF(10mL) 溶液中加入CuI(994.63mg，5.22mmol，2eq)。將混合物於N
2環境中在100℃下攪拌6小時。過濾反應混合物，並用水50mL稀釋濾液及用乙酸乙酯(50mL*2)萃取。合併的有機層用鹽水(50mL*3)洗滌，經無水Na
2SO
4乾燥，過濾並減壓濃縮濾液以得到殘餘物。透過矽膠管柱層析法(石油醚:乙酸乙酯=1:0至10:1)純化殘餘物。獲得呈黃色固體的4-溴-6-氟-N,N-二甲基-5-(三氟甲基)-1H-吲唑-7-胺 (502mg、1.54mmol、58.91%產率)。
 |
步驟1)4-溴-5-乙基-6-氟-2-三苯甲基-2H-吲唑
於N
2環境中在-78℃下向二異丙胺(132.75mg，1.31mmol，185.41uL，1.2eq)的THF(5mL)溶液中緩慢加入正丁基鋰(2.5M，481.04uL，1.1eq)0.5小時。接著將4-溴-6-氟-2-三苯甲基-2H-吲唑(500mg，1.09mmol，1eq)的THF(2mL)溶液逐滴加入到溶液中。將混合物在-78℃下攪拌0.5小時後，將EtI(204.62mg，1.31mmol，104.93uL，1.2eq)的THF(2mL)溶液加入混合物中，並將溶液加熱至15℃並在N
2環境下攪拌2小時。透過在15℃下加入3mL飽和NH
4Cl水溶液來驟冷反應混合物，用20mL的水稀釋並用乙酸乙酯(30mL*2)萃取。合併的有機層用鹽水(30mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮濾液以得到殘餘物。獲得呈黃色固體的4-溴-5-乙基-6-氟-2-三苯甲基-2H-吲唑(500mg，粗品)。
步驟2)4-溴-5-乙基-6-氟-1H-吲唑
向4-溴-5-乙基-6-氟-2-三苯甲基-2H-吲唑(500mg，1.03mmol，1eq)的DCM(6mL)溶液中加入TFA(3.08g，27.01mmol，2.00mL，26.22eq)。將混合物在15℃下攪拌4小時。用飽和NaHCO
3水溶液將反應混合物的pH值調節至7，並將混合物用二氯甲烷(30mL*2)萃取。合併的有機層用鹽水(30mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮濾液以得到殘餘物。殘餘物透過prep-HPLC(柱：Phenomenex luna C18 150*40mm*15um；流動相：[水(0.1%TFA)-ACN]；B%：40%~70%，10分鐘)純化。將分液減壓濃縮以除去ACN，用飽和NaHCO
3水溶液將水溶液的pH值調節至7。用乙酸乙酯(10mL*2)萃取水溶液。合併的有機層用鹽水(10mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮濾液以得到產物。獲得呈黃色固體的4-溴-5-乙基-6-氟-1H-吲唑(70mg，287.98umol，27.96%產率) 。
1H NMR (400MHz, DMSO-d
6) δ 13.39 (br s, 1H), 8.01 - 7.98 (m, 1H), 7.41 (d, J=9.9 Hz, 1H), 2.83 (dq, J=2.4, 7.5 Hz, 2H), 1.14 (t, J=7.5 Hz, 3H)。
 |
步驟1)6-氟-5-硝基-1H-吲唑
在-15℃下向6-氟-1H-吲唑(4.4g，32.32mmol，1
eq)的H
2SO
4(30mL)溶液中逐滴加入HNO
3(2.44g，38.79mmol，1.75mL，1.2
eq)，將反應混合物在0℃下攪拌2小時。將反應混合物緩慢倒入冰水(100mL)中，接著用乙酸乙酯(100mL*2)萃取混合物，合併的有機層經Na
2SO
4乾燥，過濾並減壓濃縮，獲得呈黃色固體的6-氟-5-硝基-1H-吲唑(5.4g，粗品)。
步驟2)6-氟-5-硝基-1-(四氫-2H-哌喃-2-基)-1H-吲唑
向6-氟-5-硝基-1H-吲唑(4.9g，27.05mmol，1
eq)(粗品)的DCM(50mL)混合物中加入DHP(6.83g，81.16mmol，7.42mL，3
eq)和TsOH.H
2O (514.60mg，2.71mmol，0.1
eq)，並將反應混合物在15℃下攪拌1小時。將反應混合物倒入NaHCO
3的飽和溶液(100mL)中，接著用二氯甲烷(50mL*2)萃取混合物，合併的有機層經Na
2SO
4乾燥，過濾並減壓濃縮至得到殘餘物。殘餘物透過管柱層析法(SiO
2，石油醚/乙酸乙酯=20/1至15:1)純化，獲得呈黃色固體的6-氟-5-硝基-1-(四氫-2H-哌喃-2-基)-1H-吲唑(3g，11.31mmol，41.81%產率)。
1H NMR (400MHz, DMSO-d
6) δ 8.78 (d,
J=7.3 Hz, 1H), 8.41 (s, 1H), 7.97 (d,
J=12.1 Hz, 1H), 5.90 (dd,
J=2.1, 9.7 Hz, 1H), 3.94 - 3.85 (m, 1H), 3.82 - 3.72 (m, 1H), 2.43 - 2.28 (m, 1H), 2.10 - 1.93 (m, 2H), 1.82 - 1.34 (m, 3H)。
步驟3)6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-5-胺
在N
2環境下，向6-氟-5-硝基-1-(四氫-2H-哌喃-2-基)-1H-吲唑(2.9g，10.93mmol，1eq)的MeOH(30mL)溶液中加入濕的Pd/C(300mg，10%純度)。將懸浮液脫氣並用H
2氣沖3次。將混合物於H
2(15 Psi)中在15℃下攪拌4小時。過濾反應混合物，並減壓濃縮濾液以得到殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯=15/1至8:1)純化殘餘物。獲得呈磚紅色固體的6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-5-胺 (1.5g，5.87mmol，53.65%產率，92%純度)。
1H NMR (400MHz, DMSO-d
6) δ 7.82 (s, 1H), 7.43 (d,
J=11.6 Hz, 1H), 6.98 (d,
J=8.6 Hz, 1H), 5.66 (dd,
J=2.3, 9.7 Hz, 1H), 4.91 (s, 2H), 3.85 (br d,
J=12.1 Hz, 1H), 3.77 - 3.62 (m, 1H), 2.42 - 2.27 (m, 1H), 2.07 - 1.96 (m, 1H), 1.95 - 1.86 (m, 1H), 1.76 - 1.63 (m, 1H), 1.59 - 1.51 (m, 2H); LCMS (電灑) m/z 236.1 (M+H)+。
步驟4)4-溴-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-5-胺
在0℃下向6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-5-胺(1.45g，5.67mmol，1eq)的MeCN(10 mL)溶液中分批加入NBS(1.21g，6.80mmol，1.2eq)。並將混合物在0℃下攪拌2小時。濃縮反應混合物以得到殘餘物。接著將殘餘物溶解在乙酸乙酯(30mL)中，混合物用鹽水(15mL*2)洗滌，有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯＝20/1)純化殘餘物。獲得呈棕色固體的4-溴-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-5-胺(1.3g，4.14mmol，72.98%產率)。
1H NMR (400MHz, DMSO-d
6) δ 7.80 (s, 1H), 7.60 (d,
J=10.6 Hz, 1H), 5.71 (dd,
J=2.5, 9.6 Hz, 1H), 5.15 (s, 2H), 3.88 - 3.82 (m, 1H), 3.76 - 3.68 (m, 1H), 2.36 - 2.27 (m, 1H), 2.02 (br dd,
J=4.6, 8.5 Hz, 1H), 1.96 - 1.90 (m, 1H), 1.76 - 1.65 (m, 1H), 1.60 - 1.52 (m, 2H)。
 |
步驟1)4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-甲醛
於N
2中，在-78℃下，向中間物1A(3g，8.99mmol，1eq)的THF(60mL)混合物中逐滴加入LDA(2M，17.99mL，4eq)。將混合物在-78℃下攪拌1小時。接著，在-78℃下逐滴加入HCO
2Et(3.17g，35.97mmol，3.52mL，4eq)的THF(8mL)溶液，接著將混合物在-78℃下攪拌2小時。在-78℃下，透過加入飽和NH
4Cl溶液(20mL)來驟冷反應混合物，接著用EA(30mL*3)萃取。合併的有機層用鹽水(30mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯=30/1至20/1)純化殘餘物。獲得呈灰白色固體的4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-甲醛(2.78g、7.69mmol、85.49%產率)。
1H NMR (400 MHz, DMSO-d
6) δ 10.40 (s, 1H), 8.35 (s, 1H), 6.09 (dd, J = 2.6, 8.9 Hz, 1H), 3.71 - 3.63 (m, 1H), 3.63 - 3.52 (m, 1H), 2.42 - 2.30 (m, 1H), 2.21 - 2.10 (m, 1H), 2.07 - 1.95 (m, 1H), 1.77 - 1.63 (m, 2H), 1.60 - 1.40 (m, 2H); LCMS (電灑) m/z 278.9 (M+H)+。
步驟2)1-(4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-基)丁-3-烯-1-醇
於N
2中，在0℃下，向4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-甲醛(2.2g，6.08mmol，1eq)的THF(60mL)混合物中逐滴加入烯丙基溴化鎂(1M，9.13mL，1.5eq)。在0℃下攪拌混合物2小時。在0℃下透過加入飽和NH
4Cl溶液(20mL)來驟冷反應混合物，接著用EA(30mL*3)萃取。合併的有機層用鹽水(30mL*2)洗滌，經無水Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯＝10/1至5/1)純化殘餘物。獲得呈無色油狀的1-(4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-基)丁-3-烯-1-醇(2g，4.95mmol，81.43%產率)。
1H NMR (400 MHz, DMSO-d
6) δ 8.25 - 8.21 (m, 1H), 8.20 - 8.18 (m, 1H), 6.61 (br d, J = 9.0 Hz, 1H), 6.23 (d, J = 4.0 Hz, 1H), 6.18 (br d, J = 8.3 Hz, 1H), 5.95 (d, J = 5.0 Hz, 1H), 5.90 - 5.75 (m, 2H), 5.36 (dt, J = 4.3, 7.5 Hz, 1H), 5.30 (td, J = 5.9, 7.9 Hz, 1H), 5.10 - 4.97 (m, 4H), 3.97 (br d, J = 11.5 Hz, 1H), 3.89 (br d, J = 11.3 Hz, 1H), 3.69 - 3.55 (m, 2H), 2.87 - 2.74 (m, 2H), 2.70 - 2.55 (m, 4H), 2.06 (br d, J = 10.8 Hz, 3H), 1.96 - 1.87 (m, 1H), 0.90 - 0.78 (m, 1H); LCMS (電灑) m/z 302.9 (M+H)+。
步驟3)4-溴-7-(3-溴環戊基)-5-氯-6-氟-1H-吲唑
於N
2中，在-20℃下，向1-(4-溴-5-氯-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑-7-基)丁-3-烯-1-醇(2g，4.95mmol，1eq)的DCM(20mL)混合物中逐滴加入Br
2(1.19g，7.43mmol，383.11uL，1.5eq)的DCM(2mL)混合物。混合物在-10℃下攪拌3小時。透過加入Na
2SO
3溶液(30mL)驟冷混合物，接著用DCM(30mL)稀釋。有機層用Na
2SO
3溶液(30mL*2)洗滌，經無水Na
2SO
4乾燥，過濾並濃縮以獲得殘餘物。將殘餘物溶解在MeOH(15mL)中，接著加入K
2CO
3(2.05g，14.86mmol，3eq)並將所得混合物在20℃下攪拌16小時。加入水(20mL)驟冷反應，用EA(30mL*3)萃取，經Na
2SO
4乾燥，過濾並濃縮以獲得殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯＝10/1至3:1)純化殘餘物。透過反相HPLC(0.1% FA條件)純化粗產物。獲得呈白色固體的4-溴-7-(3-溴環戊基)-5-氯-6-氟-1H-吲唑 (300mg，752.91umol，15.20%產率)。
1H NMR (400 MHz, DMSO-d
6) δ 13.44 - 13.37 (m, 2H), 8.14 - 8.11 (m, 2H), 5.71 - 5.67 (m, 1H), 5.44 (dt, J = 1.2, 7.5 Hz, 1H), 4.97 (s, 1H), 4.83 - 4.76 (m, 2H), 4.47 (dd, J = 3.7, 10.1 Hz, 1H), 4.22 (dd, J = 5.5, 10.1 Hz, 1H), 4.15 (dd, J = 2.3, 10.6 Hz, 1H), 3.20 - 3.13 (m, 1H), 2.69 - 2.64 (m, 1H), 2.34 - 2.27 (m, 2H); LCMS (電灑) m/z 398.8 (M+H)+。
步驟4)3-(4-溴-5-氯-6-氟-1H-吲唑-7-基)乙酸環戊酯
於N
2中，在20℃下，向4-溴-7-(3-溴環戊基)-5-氯-6-氟-1H-吲唑(100mg，250.97μmol，1eq)的DMSO(2mL)混合物中加入一份KOAc(73.89mg，752.91μmol，3eq)。接著將混合物加熱至70℃並攪拌3小時。加入水(15mL)驟冷反應，接著用EA(20mL*3)萃取，合併的有機層用鹽水(20mL*2)洗滌，經Na
2SO
4乾燥，過濾並濃縮以得到殘餘物。3-(4-溴-5-氯-6-氟-1H-吲唑-7-基)乙酸環戊酯(100mg，粗品，棕色油狀)不經進一步純化直接用於下一步。
LCMS(電灑)m/z 378.8 (M+H)+。
步驟5)3-(4-溴-5-氯-6-氟-1H-吲唑-7-基)環戊烷-1-醇
於N
2中，在20℃下，向3-(4-溴-5-氯-6-氟-1H-吲唑-7-基)乙酸環戊酯(80mg，211.87umol，1eq)的MeOH(4mL)和H2O(0.8mL)混合物中加入一份K
2CO
3(442.15mg，3.20mmol，15.1eq)。在20℃下攪拌混合物2小時。在20℃下透過加入水(15mL)來驟冷反應混合物，接著用乙酸乙酯(20mL*3)萃取。合併的有機層用鹽水(20mL*1)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯＝3/1至1/2)純化殘餘物。獲得呈白色固體的3-(4-溴-5-氯-6-氟-1H-吲唑-7-基)環戊烷-1-醇(50mg，149.01umol，70.33%產率)。
LCMS(電灑)m/z 336.9 (M+H)+。
步驟1)5-氟-2-碘-4-(三氟甲基)苯胺
在15℃下向3-氟-4-(三氟甲基)苯胺(4g，22.33mmol，1eq)的MeCN(40mL)溶液中加入 NIS(5.53g，24.57mmol，1.1eq)，接著將反應混合物在15℃下攪拌15小時。用H
2O (100mL)稀釋反應混合物，並用EtOAc(100mL*3)萃取。合併的有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。獲得呈棕色油狀的5-氟-2-碘-4-(三氟甲基)苯胺(5.6g，粗品)。
LCMS(電灑)m/z 305.9 (M+H)+。
步驟2)5-氟-2-甲基-4-(三氟甲基)苯胺
在15℃下，向5-氟-2-碘-4-(三氟甲基)苯胺(6.0g，19.67mmol，1eq)及2,4,6-三甲基-1,3,5,2,4,6-三氧雜三硼雜環己烷(8.82g，29.51mmol，9.82mL，42%純度，1.5eq)的DME (60 mL)溶液中加入Pd(PPh
3)
4(1.14g，983.57umol，0.05eq) 及K
2CO
3(8.16g，59.01mmol，3eq)，接著將反應混合物在100℃下攪拌60小時。減壓濃縮反應混合物以提供殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯＝5/1至3/1，石油醚/乙酸乙酯=2:1，Rf=0.3)純化殘餘物。獲得呈黃色油狀的5-氟-2-甲基-4-(三氟甲基)苯胺(1.6g，4.06mmol，20.64%產率，49%純度)。
LCMS(電灑)m/z 194.1.9 (M+H)+。
步驟3)6-氟-5-(三氟甲基)-1H-吲唑
在0℃下向5-氟-2-甲基-4-(三氟甲基)苯胺(1g，5.18mmol，1eq)的AcOH(15mL)溶液中加入NaNO
2(357.25mg，5.18mmol，1eq)及H
2O(3mL)，接著將反應混合物在15℃下攪拌2小時。透過在20℃下加入H
2O(60mL)驟冷反應，並用EtOAc(50mL*3)萃取所得混合物。合併的有機層用H
2O(50mL*3)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過管柱(SiO2，石油醚/乙酸乙酯＝10/1至5/1，石油醚/乙酸乙酯=3:1，Rf=0.5)純化殘餘物。獲得呈黃色固體的6-氟-5-(三氟甲基)-1H-吲唑(500mg，2.45mmol，47.31%產率)。
LCMS(電灑)m/z 205.2 (M+H)+。
步驟4)6-氟-7-硝基-5-(三氟甲基)-1H-吲唑
在0℃下向6-氟-5-(三氟甲基)-1H-吲唑(500mg，2.45mmol，1eq)的H
2SO
4(5mL，95%純度)溶液中加入KNO
3(249mg，2.46mmol，1.01eq)，接著將反應混合物在15℃下攪拌15小時。用水(100mL)稀釋反應混合物並用乙酸乙酯(50mL*2)萃取。合併的有機層用飽和碳酸氫鈉溶液處理至pH=7，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。獲得呈黃色固體的6-氟-7-硝基-5-(三氟甲基)-1H-吲唑(500mg)。
LCMS(電灑)m/z 250.2 (M+H)+。
步驟5)6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑
在0℃下，向6-氟-7-硝基-5-(三氟甲基)-1H-吲唑(500mg，2.01mmol，1eq)的THF(10mL)溶液中加入PPTS (50.44mg，200.71umol，0.1eq)及DHP(844.13mg，10.04mmol，917.53uL，5eq)，接著在60℃下將反應混合物攪拌15小時。用溶劑H
2O(50mL)稀釋反應混合物，並用EtOAc(50mL*3)萃取。合併的有機層用H
2O(50mL*3)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。獲得呈黃色油狀的6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑(1g，粗品)。
步驟6)6-氟-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑-7-胺
在0℃下，向6-氟-7-硝基-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑(800mg，2.40mmol，1eq)及H
2O(2mL)的EtOH(10mL)溶液中加入NH
4Cl(642.08mg，12.00mmol，5eq) 及Fe(268.13mg，4.80mmol，2eq)，接著將反應混合物在60℃下攪拌1小時。用H
2O(20mL)稀釋反應混合物，並用EtOAc(20mL*3)萃取。合併的有機層用H
2O(30mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯＝10/1至5/1，石油醚:乙酸乙酯=3:1，Rf=0.3)純化殘餘物。獲得呈黃色固體的6-氟-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑-7-胺(500mg，1.65mmol，68.68%產率)。
LCMS(電灑)m/z 220.2 (M+H)+。
步驟7)4-溴-6-氟-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑-7-胺
在20℃下向6-氟-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑-7-胺(200mg，659.51umol，1eq)的DMF(1mL)溶液中加入NBS(129.12mg，725.46umol，1.1eq)，接著將反應混合物在20℃下攪拌2小時。用H
2O(10mL)稀釋反應混合物，並用EtOAc(10mL*3)萃取。合併的有機層用H
2O(10mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。獲得呈黃色固體的4-溴-6-氟-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑-7-胺(120mg，粗品)。
LCMS(電灑)m/z 297.9 (M+H)+。
步驟8) 4-溴-6-氟-N-異丙基-5-(三氟甲基)-1H-吲唑-7-胺
在20℃下向4-溴-6-氟-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑-7-胺(100mg，335.53umol，1eq)的MeOH(1mL)溶液中加入AcOH(40.30mg，671.06umol，38.38uL，2eq)及丙酮(97.44mg，1.68mmol，123.34uL，5eq)，接著加入NaBH
3CN(105.42mg，1.68mmol，5eq)並將反應混合物在20℃下攪拌2小時。接著，將丙酮(97.44mg，1.68mmol，123.34uL，5eq)、NaBH
3CN(105.43mg，1.68mmol，5eq)及AcOH(60.45mg，1.01mmol，57.57uL，3eq)加入到混合物中，並在20℃下攪拌反應混合物20小時。用H
2O(10mL)稀釋反應混合物，並用EtOAc(10mL*3)萃取。合併的有機層用H
2O(10mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過prep-TLC(石油醚/乙酸乙酯＝3:1，Rf=0.4)純化殘餘物。獲得呈白色固體的4-溴-6-氟-N-異丙基-5-(三氟甲基)-1H-吲唑-7-胺(60mg，165.83umol，49.42%產率，94%純度)。
LCMS(電灑)m/z 340.1 (M+H)+。
步驟9)4-溴-6-氟-N-異丙基-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑-7-胺
在0℃下，向4-溴-6-氟-N-異丙基-5-(三氟甲基)-1H-吲唑-7-胺(50mg，147.01umol，1eq)的THF(1mL)溶液中加入PPTS(3.69mg，14.70umol，0.1eq)及DHP(61.83mg，735.05umol，67.21uL，5eq)，接著在60℃下將反應混合物攪拌2小時。用H
2O(50mL)稀釋反應混合物，並用EtOAc(50mL*3)萃取。合併的有機層用H
2O(50mL*3)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過prep-TLC(石油醚:乙酸乙酯=5:1，Rf=0.6)純化殘餘物。獲得呈黃色油狀的4-溴-6-氟-N-異丙基-2-(四氫-2H-哌喃-2-基)-5-(三氟甲基)-2H-吲唑-7-胺(50mg，117.86umol，80.17%產率)。
LCMS(電灑)m/z 424.1 (M+H)+。
 |
步驟1)3-溴-5-氟-2-甲基苯胺
向1-溴-5-氟-2-甲基-3-硝基苯(23g，98.28mmol，1
eq)的EtOH(80mL)及H
2O(80mL)的混合物中加入Fe(27.44g，491.41mmol，5
eq) 及NH
4Cl(26.29g，491.41mmol，5
eq)。將混合物在100℃下攪拌3小時。過濾混合物並減壓濃縮濾液以除去EtOH。所得混合物用DCM(50mL*3)萃取。合併的有機相用鹽水(50mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物以得到呈黃色液體的3-溴-5-氟-2-甲基苯胺(20.6g，粗品)。
1H NMR (400MHz, DMSO-d
6) δ 6.59 (br d, J=8.4 Hz, 1H), 6.42 (br d, J=11.2 Hz, 1H), 5.51 (br s, 2H), 2.09 (s, 3H)。
步驟2)3-溴-5-氟-4-碘-2-甲基苯胺
在0℃下，向3-溴-5-氟-2-甲基苯胺(18g，88.22mmol，1eq)(粗品)的CH
3CN(150mL)混合物中分批加入NIS(19.85g，88.22mmol，1eq)。將混合物在30℃下攪拌3小時。3小時後，LCMS顯示化合物2殘留，且亦檢測期望的質量。接著將混合物在30℃下再另外攪拌12小時。LCMS顯示沒有化合物2殘留且檢測到一個具有期望質量的主峰。用飽和Na
2SO
3(200mL)驟冷混合物並用EtOAc(50mL*3)萃取所得混合物。合併的有機相用鹽水(50mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。殘餘物透過矽膠層析法(1000篩孔矽膠，石油醚/乙酸乙酯=50/1，30/1、TLC(石油醚:乙酸乙酯=10:1，Rf=0.28))純化，以得到呈棕色固體的3-溴-5-氟-4-碘-2-甲基苯胺(22g，66.68mmol，75.58%產率)。
1H NMR (400MHz, DMSO-d
6) δ 6.55 (d, J=10.5 Hz, 1H), 5.67 (s, 2H), 2.25 (d, J=0.8 Hz, 3H)。
步驟3)4-溴-6-氟-5-碘-1H-吲唑
在0℃下，向3-溴-5-氟-4-碘-2-甲基苯胺(22g，66.68mmol，1eq)的CH
3COOH(200mL)混合物中加入溶解於水(40mL)的NaNO
2(5.52g，80.02mmol，1.2eq)。將混合物在30℃下攪拌16小時。將混合物倒入飽和NaHCO
3(1000mL)中並用EtOAc(200mL*3)萃取所得混合物。合併的有機相用鹽水(100mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。殘餘物經矽膠層析法(1000篩孔矽膠，石油醚/乙酸乙酯=15/1，5/1)純化，以得到呈棕色固體的4-溴-6-氟-5-碘-1H-吲唑(7.5g，22.00mmol，32.99%產率)。
1H NMR (400MHz, DMSO-d
6) δ 13.58 (br s, 1H), 8.00 (s, 1H), 7.51 (d, J=8.1 Hz, 1H), 3.32 (s, 1H)。
步驟4)4-溴-6-氟-5-碘-1-(四氫-2H-哌喃-2-基)-1H-吲唑
向4-溴-6-氟-5-碘-1H-吲唑(7.5g，22.00mmol，1eq)及4-甲基苯磺酸水合物(418.47mg，2.20mmol，0.1eq)的DCM(100mL)混合物中緩慢加入DHP(5.55g，66.00mmol，6.03mL，3eq)。將混合物在30℃下攪拌1小時。混合物用飽和NaHCO
3(30mL*3)及鹽水(30mL*3)洗滌。有機相經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。殘餘物經矽膠層析法(1000篩孔矽膠，石油醚/乙酸乙酯=100/1，50/1)純化，以得到呈黃色固體的4-溴-6-氟-5-碘-1-(四氫-2H-哌喃-2-基)-1H-吲唑(7.4g，17.41mmol，79.14%產率)。
1H NMR (400MHz, DMSO-d
6) δ 8.06 (s, 1H), 7.80 (dd, J=0.7, 8.4 Hz, 1H), 5.83 (dd, J=2.4, 9.6 Hz, 1H), 3.88 - 3.85 (m, 1H), 3.80 - 3.70 (m, 2H), 2.40 - 2.27 (m, 1H), 2.07 - 1.94 (m, 2H), 1.81 - 1.63 (m, 2H), 1.62 - 1.53 (m, 2H)。
步驟5)4-溴-5-環丙基-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑
於N
2中，向4-溴-6-氟-5-碘-1-(四氫-2H-哌喃-2-基)-1H-吲唑(1.5g，3.53mmol，1eq) 及環丙基硼酸(303.14mg，3.53mmol，1eq)的二噁烷(10 mL) 及H
2O(2.5mL)的混合物中加入Na
2CO
3(748.10mg，7.06mmol，2eq) 及Pd(dppf)Cl
2(258.23mg，352.91μmol，0.1eq)。將混合物在80℃下攪拌16小時。減壓濃縮混合物以得到殘餘物。殘餘物透過prep-TLC(石油醚：乙酸乙酯=20:1)純化以得到呈無色油狀的4-溴-5-環丙基-6-氟-1-(四氫-2H-哌喃-2-基)-1H-吲唑(0.21g，619.10umol，17.54%產率)。
1H NMR (400MHz, CDCl
3) δ 7.98 (d, J=0.6 Hz, 1H), 7.20 (d, J=10.4 Hz, 1H), 5.61 (dd, J=2.8, 9.1 Hz, 1H), 4.03 - 3.94 (m, 1H), 3.76-3.69 (m, 1H), 2.55 - 2.42 (m, 1H), 2.19 - 2.06 (m, 2H), 1.91-1.86 (m, 1H), 1.81 - 1.64 (m, 3H), 1.12 - 1.05 (m, 2H), 0.87 - 0.81 (m, 2H)。
步驟1)4-溴-6-氟-5-(丙-1-烯-2-基)-1-(四氫-2H-哌喃-2-基)-1H-吲唑
於N
2中，向4-溴-6-氟-5-碘-1-(四氫-2H-哌喃-2-基)-1H-吲唑(1.5g，3.53mmol，1
eq)及三氟(異丙烯基)硼氫化鉀(626.67mg，4.23mmol，1.2
eq)的二噁烷(10mL) 及H
2O(2mL)的混合物中加入Pd(dppf)Cl
2(258.23mg，352.91umol，0.1
eq) 及Na
2CO
3(748.10mg，7.06mmol，2
eq)。將混合物在80℃下攪拌16小時。減壓濃縮混合物以得到殘餘物。殘餘物透過矽膠層析法(1000目矽膠，石油醚/乙酸乙酯=100/1，50/1、TLC(石油醚:乙酸乙酯=10:1，Rf=0.61))純化以得到0.9g的黃色油。此油透過prep-TLC(石油醚：乙酸乙酯=20:1)純化以得到呈黃色油狀的4-溴-6-氟-5-(丙-1-烯-2-基)-1-(四氫-2H-哌喃-2-基)-1H-吲唑(0.55g，1.62mmol，45.94%產率)。
1H NMR (400MHz, CDCl
3) δ 8.00 (d,
J=0.6 Hz, 1H), 7.28 (d,
J=0.9 Hz, 0.5H), 7.26 (d,
J=0.7 Hz, 0.5H), 5.64 (dd,
J=2.8, 9.0 Hz, 1H), 5.46 (t,
J=1.6 Hz, 1H), 5.01 (s, 1H), 4.05 - 3.97 (m, 1H), 3.80 - 3.69 (m, 1H), 2.57 - 2.42 (m, 1H), 2.19 - 2.09 (m, 2H), 2.07 (s, 3H), 1.81 - 1.66 (m, 4H)。
步驟2)4-溴-6-氟-5-異丙基-1-(四氫-2H-哌喃-2-基)-1H-吲唑
於N
2中，向4-溴-6-氟-5-(丙-1-烯-2-基)-1-(四氫-2H-哌喃-2-基)-1H-吲唑(0.4g，1.18mmol，1
eq)的MeOH(10mL)溶液中加入PtO
2。將懸浮液在真空下脫氣並用H
2氣沖數次。將混合物在H
2(15Psi)下在30℃下攪拌2.5小時。過濾混合物並減壓濃縮濾液以得到殘餘物。殘餘物透過矽膠層析法(300~400篩孔矽膠，石油醚/乙酸乙酯=50/1)純化以得到呈無色油狀的4-溴-6-氟-5-異丙基-1-(四氫-2H-哌喃-2-基)-1H-吲唑(0.3g，879.20umol，74.56%產率)。
步驟3)4-溴-6-氟-5-異丙基-1H-吲唑
向4-溴-6-氟-5-異丙基-1-(四氫-2H-哌喃-2-基)-1H-吲唑(0.3g，879.20umol，1eq) 的DCM(1mL)溶液中加入TFA(2.30g，20.14mmol，1.49mL，22.91eq)。將混合物在 30℃下攪拌0.5小時。減壓濃縮混合物以得到殘餘物。殘餘物用DCM(10mL)稀釋並用TEA將所得混合物調節pH至約8。減壓濃縮混合物以得到殘餘物。殘餘物經矽膠層析法(300~400篩孔矽膠，石油醚/乙酸乙酯=30/1、5/1)純化以得到呈無色油狀的4-溴-6-氟-5-異丙基-1H-吲唑(0.2g，777.90umol，88.48%產率)。
1H NMR (400MHz, CDCl
3) δ 8.04 (s, 1H), 7.11 (d, J=11.2 Hz, 1H), 3.75 - 3.63 (m, 1H), 1.38 (dd, J=1.7, 7.1 Hz, 6H)。
 |
步驟1)2-溴-4-氟-3-甲氧基-1-甲基苯
向2-溴-6-氟-3-甲苯酚(4.8g，23.41mmol，1
eq)的丙酮(50mL)溶液中加入K
2CO
3(6.47g，46.82mmol，2
eq)和碘甲烷(9.97g，70.24mmol，4.37mL，3
eq)，並將混合物在25℃下攪拌1小時。濃縮反應混合物以得到殘餘物。將殘餘物溶於乙酸乙酯(50mL)中，並過濾混合物，再濃縮濾液以得到呈黃色油狀的殘餘物(4.6g，21.00mmol，89.70%產率)。
1H NMR (400MHz, CHLOROFORM-d) δ 7.05 - 6.85 (m, 2H), 3.95 (d,
J=1.2 Hz, 3H), 2.38 (s, 3H)。
步驟2)3-溴-1-氟-2-甲氧基-4-甲基-5-硝基苯
在0℃下向2-溴-4-氟-3-甲氧基-1-甲基苯(4.4g，20.09mmol，1
eq)的H
2SO
4(40mL)(98%)溶液中分批加入KNO
3(2.23g，22.10mmol，1.1
eq)，並將混合物在25℃下攪拌1小時。將反應混合物緩慢倒入冰水(200mL)中，接著用乙酸乙酯(200mL*2)萃取混合物，合併的有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。獲得呈棕色油狀的3-溴-1-氟-2-甲氧基-4-甲基-5-硝基苯(4.6g，粗品)。
1H NMR (400MHz, CHLOROFORM-d) δ 7.70 (d,
J=10.9 Hz, 1H), 4.08 (d,
J=2.7 Hz, 3H), 2.61 (d,
J=1.1 Hz, 3H)。
步驟3)3-溴-5-氟-4-甲氧基-2-甲基苯胺
向3-溴-1-氟-2-甲氧基-4-甲基-5-硝基苯(4.6g，17.42mmol，1
eq)的EtOH(30mL)及H
2O(30mL)的溶液中加入Fe(5.84g，104.53mmol，6
eq)及NH
4Cl(5.59g，104.53mmol，6
eq)，並將混合物在80℃下攪拌2小時。過濾反應混合物，並將濾液濃縮以除去EtOH，接著用EA(50mL)稀釋混合物，並用水(20mL*2)洗滌混合物，接著有機層經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。獲得呈棕色油狀的3-溴-5-氟-4-甲氧基-2-甲基苯胺(3.5g，粗品)。
1H NMR (400MHz, CHLOROFORM-d) δ 6.44 (d,
J=11.9 Hz, 1H), 3.83 (s, 3H), 3.76 - 3.48 (m, 2H), 2.24 (d,
J=1.0 Hz, 3H)。
步驟4)4-溴-6-氟-5-甲氧基-1H-吲唑
在0℃下向3-溴-5-氟-4-甲氧基-2-甲基苯胺(3.5g，14.95mmol，1
eq)(粗品)的AcOH (20mL)混合物中逐滴加入NaNO
2(1.24g，17.94mmol，1.2
eq)的H
2O(4mL)溶液，接著將混合物在25℃下攪拌12小時。將反應混合物用冰水(100mL)稀釋，並透過使用KOH將混合物調節至pH7，接著用EA(100mL*2)萃取混合物，合併的有機層用鹽水(50mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮以得到殘餘物。透過管柱層析法(SiO
2，石油醚/乙酸乙酯＝20/1至15:1)純化殘餘物。獲得呈棕色固體的4-溴-6-氟-5-甲氧基-1H-吲唑(600mg，2.45mmol，16.37%產率)。
1H NMR (400MHz, DMSO-d
6) δ 13.44 (br s, 1H), 8.00 (s, 1H), 7.52 (br d,
J=10.4 Hz, 1H), 3.84 (s, 3H)。
式
(I)
化合物的合成
使用合成方法A~J製備以下化合物。下述描述本發明中一些化合物之說明性合成實例，且其他化合物可透過與下述所述方法類似之方法用不同的起始或反應材料製備而得。
合成方法
A
 |
向
化合物 1(0.2 g，0.462 mmol，1 eq)(5-甲基-1H-吲唑-4-基)硼酸(0.081 g，0.462 mmol，1 eq)在二噁烷(4 mL)及H
2O(1 mL)中的溶液中加入Na
2CO
3(0.146 g，1.38 mmol，3 eq)及Pd(dppf)Cl
2(33 mg，0.046 mmol，0.1 eq)。將混合物在110℃下攪拌16小時。將反應混合物用水(10ml)稀釋，並用乙酸乙酯(10ml x 2)萃取。合併的有機層經Na
2SO
4乾燥，過濾並減壓濃縮，得到殘餘物。藉由管柱層析法純化殘餘物，獲得為黃色固體的
實施例 2(135 mg，0.369 mmol，80% 產率)。
1H NMR (400 MHz, DMSO-d
6) δ 13.04 (s, NH), 12.76 (s, CONH), 8.05 (s, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.63 (s, 2H), 7.49-7.44 (m, 2H), 7.31 (d, J=8.4 Hz, 1H), 5.05 (td, J12=3.3 Hz, J13=65.7 Hz, 1H), 2.24 (s, 3H), 2.23-2.24 (m, 1H), 1.78-1.73 (m, 1H), 1.31-1.23 (m, 1H); LCMS (電噴霧) m/z 367.1 (M+H)+。
合成方法
B
 |
步驟1)(1S,2S)-N-(6-(5-氯-6-氟-7-(甲硫基)-2-(四氫-2H-吡喃-2-基)-2H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺
在N
2下，向
化合物 3(4.4 g，11.59 mmol，1 eq)在二噁烷(100 mL)和H
2O(20 mL)的溶液中加入化合物2(4.20 g，11.59 mmol，1 eq)、Pd(dppf)Cl
2(847.97 mg，1.16 mmol，0.1 eq)和Na
2CO
3(2.46 g，23.18 mmol，2 eq)。將反應混合物在90°C下攪拌12小時。加入水(100 mL)，並用EA(200 mL*2)萃取所得水相。合併的有機相用飽和鹽水(200ml*2)洗滌，並在真空中濃縮。藉由矽膠層析法(石油醚：乙酸乙酯=10:1至1:1)純化混合物，獲得為淡黃色固體
化合物 4(3.9 g，7.29 mmol，62.90%產率)。
1H NMR (400MHz, DMSO-d
6) δ 8.00 - 7.95 (m, 2H), 7.92 - 7.85 (m, 1H), 7.59 (dd, J=1.8, 8.4 Hz, 1H), 5.70 (dd, J=2.5, 9.5 Hz, 1H), 5.07 - 4.79 (m, 1H), 3.82 - 3.63 (m, 1H), 2.72 (d, J=0.9 Hz, 3H), 2.35 - 2.23 (m, 1H), 2.04 - 1.94 (m, 2H), 1.81 - 1.48 (m, 4H), 1.46 - 1.33 (m, 2H)。
步驟2)(1S, 2S)-N-(6-(5-氯-6-氟-7-(甲硫基)-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺。2 TFA鹽
在N
2下，向
化合物 4(3.80 g，7.10 mmol，1 eq)在DCM(100 mL)的溶液中加入TFA(9.86 g，86.51 mmol，6.41 mL，12.18 eq)。將反應混合物在20℃下攪拌4小時。加入DCM(10 ml)，接著緩慢添加MeOH(200 ml)。將反應混合物在20℃下攪拌半小時。過濾反應混合物並濃縮濾餅以得到產物。濾液在真空中濃縮得到產物。接著將粗產物凍乾，得到為淡黃色固體的
實施例 58(3.1 g，4.26 mmol，59.98%產率，2 TFA)。
1H NMR (400MHz, DMSO-d
6) δ 13.76 (br s, 1H), 12.82 (br s, 1H), 8.19 (d, J=1.7 Hz, 1H), 7.96 - 7.82 (m, 2H), 7.59 (dd, J=1.8, 8.4 Hz, 1H), 5.26 - 4.85 (m, 1H), 2.57 (s, 3H), 2.30 - 2.19 (m, 1H), 1.84 - 1.69 (m, 1H), 1.33 (tdd, J=6.4, 9.0, 12.9 Hz, 1H); LCMS (電噴霧) m/z 450.8 (M+H)+。
合成方法
C
實施例149。(1S,2S)-N-(5-(5-氯-7-乙氧基-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺。2 TFA
向
化合物 5(2.5 g，7.91 mmol，1 eq)在二噁烷(30 mL)的溶液中加入(SnBu
3)
2(6.88 g，11.86 mmol，5.93 mL，1.5 eq)、Pd(PPh
3)
4(913.78 mg，790.77 umol，0.1 eq)及LiCl(1.01 g，23.72 mmol，485.85 uL，3 eq)。將反應混合物在N
2下在110℃下攪拌16小時。過濾反應混合物，並減壓濃縮濾液，得到殘餘物。藉由管柱層析法(矽膠，石油醚：乙酸乙酯=10:1至3:1)純化殘餘物。獲得為黃色油狀的
化合物 6(1.3g，2.47mmol，31.24%產率)。
步驟2)(1S,2S)-N-(5-(5-氯-7-乙氧基-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺。2 TFA
向4-溴-5-氯-7-乙氧基-6-氟-1H-吲唑(100 mg，264.81 umol，1 eq)在二噁烷(2 mL)的溶液中加入
化合物 6(167.24 mg，317.77 umol，1.2 eq)、Pd(PPh
3)
4(30.60 mg，26.48 umol，0.1 eq)及LiCl(33.68 mg，794.42 umol，16.27 uL，3 eq)。將混合物在140℃下在微波下攪拌2小時。接著，向反應混合物中添加10 mL飽和K
2CO
3水溶液，並在20°C下攪拌15分鐘。用10 mL水稀釋混合物，並用乙酸乙酯(20 mL*2)萃取。用鹽水(20 mL*2)洗滌合併的有機層，合併的有機層經Na
2SO
4乾燥，過濾並減壓濃縮，得到殘餘物。藉由prep-TLC(矽膠板，石油醚：乙酸乙酯=1:2)純化殘餘物，得到粗產物。藉由prep -HPLC(柱：Phenomenex luna C18 150*25mm*10um；流動相：[水(0.1%TFA)-ACN]；B%：55%~85%，10分鐘)純化粗產物。得到為黃色油狀的
實施例 149(60 mg，112.36μmol，42.43%產率)。
1H NMR (400MHz, DMSO-d
6) δ 12.97 (s, 1H), 8.28 (d, J=8.4 Hz, 1H), 7.95 (s, 1H), 7.81 (d, J=8.4 Hz, 1H), 6.12 - 6.06 (m, 1H), 5.20 - 4.96 (m, 1H), 4.46 - 4.34 (q, J=7.0 Hz, 2H), 3.97 (m, 1H), 3.73 - 3.61 (m, 1H), 2.47 - 2.40 (m, 1H), 2.32 - 2.22 (m, 1H), 2.04 (m, 2H), 1.83 - 1.69 (m, 2H), 1.57 (m, 2H), 1.49 (t, J=7.0 Hz, 3H), 1.41 - 1.28 (m, 1H)。
合成方法
D
 |
向
中間物 1K(45 mg，185.13 umol，1 eq)在EtOH(2 mL)的溶液中加入
化合物 6(116.92 mg，222.15 umol，1.2 eq)及Ad
2nBuP-Pd-G
3(13.48 mg，18.51 umol，0.1 eq)。接著將反應混合物在N
2環境下在80℃下攪拌16小時。將反應混合物用水20 mL稀釋，並用乙酸乙酯(20 mL*2)萃取。用鹽水(20 mL*2)洗滌合併的有機層，合併的有機層經Na
2SO
4乾燥，過濾，並在減壓下濃縮濾液，得到殘餘物。藉由prep-HPLC(柱：Phenomenex luna C18 150*25mm*10um；流動相：[水(0.1%TFA)-ACN]；B%：33%~63%，10分鐘)純化殘餘物，得到粗產物。粗產物藉由prep-TLC(矽膠板，石油醚：乙酸乙酯=1:1)純化。得到白色固體的
實施例 152(9.7 mg，24.29 umol，13.12%產率，100%純度)。
1H NMR (400 MHz, DMSO-d
6) δ 13.18 (br s, 1H), 12.94 (br s, 1H), 8.26 (d, J=8.2 Hz, 1H), 7.72 (s, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.42 (d, J=10.1 Hz, 1H), 5.20 - 4.95 (m, 1H), 2.65 (dq, J=2.4, 7.2 Hz, 2H), 2.27 (m, 1H), 1.85 - 1.69 (m, 1H), 1.34 (m, 1H), 1.11 (t, J=7.0 Hz, 3H); LCMS (電噴霧) m/z 400.4 (M+H)+。
合成方法
E
 |
步驟1)(1S,2S)-2-氟-N-(6-碘代咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺
在室溫下用N,N-二異丙基乙胺(2.376 mL，13.642 mmol)處理二氯甲烷(100 mL)中5之
化合物 7(5.890 g，22.737 mmol)、(1S,2S)-2-氟環丙烷-1-羧酸(3.076 g，29.558 mmol)及1-乙基-3-(3-二甲胺基丙基)碳二亞胺鹽酸鹽(EDC-HCl，6.538 g，34.105 mmol)的混合物，在相同溫度下攪拌40小時。藉由過濾收集沉澱物，用二氯甲烷洗滌，並乾燥，得為米黃色固體的
化合物 8(3.870 g，49.3%)。
1H NMR (400 MHz, DMSO-d
6) δ 10.99 (s, 1H), 8.87 (s, 1H), 8.02 (s, 1H), 7.36 ~ 7.23 (m, 2H), 4.97 ~ 4.77 (m, 1H), 2.09 ~ 2.07 (m, 1H), 1.65 ~ 1.57 (m, 1H), 1.16 ~ 1.09 (m, 1H)。
步驟2)(1S,2S)-2-氟-N-(6-(5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺
化合物 8(0.750 g，2.173 mmol)、(5-甲基-1H-吲唑-4-基)硼酸(0.459 g，2.608 mmol)、[1,1'-雙(二苯基膦基)二茂鐵]二氯鈀(II)(Pd(dppf)Cl
2，0.159 g，0.217 mmol)及碳酸銫(1.416 g，4.346 mmol)在四氫呋喃(15 mL)/水中(4 mL)於室溫下混合，接著在微波下於120°C下加熱1小時，冷卻至室溫，藉由矽藻土墊過濾以去除固體，並在乙酸乙酯及飽和碳酸氫鈉水溶液之間分離。用飽和氯化鈉水溶液清洗有機層，分離有機層、乾燥(無水硫酸鎂)、過濾，並在真空中濃縮。對殘餘物進行色譜分析(SiO
2，30 g筒；乙酸乙酯/己烷=100%)，得到粗產物，在室溫下使用乙醚(5 mL)使粗產物結晶。過濾所得沉澱物，用乙醚洗滌並乾燥沉澱物，得到為淡黃色固體的
實施例 221(0.550 g，72.4%)。
1H NMR (400MHz, DMSO-d
6) δ 12.77 (s, 1H), 9.70 (s, 1H), 9.00 (s, 1H), 8.66 (d, J = 9.2 Hz, 1H), 8.59 (s, 1H), 8.55 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 5.91 ~ 5.71 (m, 1H), 3.11 (s, 3H), 3.05 ~ 3.00 (m, 1H), 2.54 ~ 2.48 (m, 1H), 2.07 ~ 2.03 (m, 1H); LCMS (電噴霧) m/z 350.0 (M+H)+。
合成方法
F
實施例223。N-(6-(5-氯-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷甲醯胺鹽酸
向環丙烷羧酸(3.17 g，36.78 mmol，2.91 mL，1.3 eq)在DCM(50 mL)的溶液中加入EDCI(6.51 g，33.95 mmol，1.2 eq)、HOBt(4.59 g，33.95 mmol，1.2 eq)及TEA(8.59 g，84.89 mmol，11.82 mL，3 eq)。將混合物在20℃下攪拌1小時。接著添加
化合物 7(6 g，28.30 mmol，1 eq)。最終將混合物在20°C下攪拌18小時。將混合物倒入H
2O(200 mL)中，用乙酸乙酯(300 mL*3)萃取，用鹽水(500 mL*2)洗滌有機相，經無水硫酸鈉(Na
2SO
4)乾燥，過濾並在真空中濃縮。殘餘物用乙酸乙酯(50 mL)研磨純化，過濾並濃縮濾餅，得到為黃色固體的
化合物 9(1.9g，6.78mmol，23.96%產率)。
1H NMR (400MHz, DMSO-d
6) δ 9.70 (d, J=1.2 Hz, 1H), 7.60 (dd, J=2.1, 9.3 Hz, 1H), 7.32 (d, J=9.3 Hz, 1H), 6.62 (s, 2H), 2.46 - 2.37 (m, 1H), 1.02 - 0.90 (m, 4H)。
步驟2)(1S,2S)-2-氟-N-(6-(5-甲基-1H-吲哚-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺二鹽酸鹽
向
化合物 9(10.22 g，31.27 mmol，1 eq)及4,4,5,5-四甲基-2-(4,4,5,5-四甲基-1,3,2-二氧苯甲醛-2-基)-1,3,2-二氧苯甲醛(11.12 g，43.78 mmol，1.4
eq)在二噁烷(100 mL)的溶液中加入KOAc(9.21 g，93.82 mmol，3
eq)及Pd(dppf)Cl
2(1.14 g，1.56 mmol，0.05
eq)。將混合物加熱至90°C 3小時。將殘餘物倒入水(200 mL)中。用乙酸乙酯(200ml*2)萃取水相。用鹽水(300 mL)洗滌合併的有機相，有機相經無水Na
2SO
4乾燥，過濾並在真空中濃縮。TLC(石油醚/乙酸乙酯=0:1)顯示一個主要點。藉由矽膠層析法純化殘餘物，用石油醚/乙酸乙酯=0:1洗脫。得到
化合物 10(11g，粗品)，其為黃色固體。用石油醚(20ml)及乙酸乙酯(4ml)研磨純化粗產物，過濾並濃縮濾餅。得到為白色固體的
化合物 10(6.3g，19.26mmol，產率48.46%)。
步驟3)N-(6-(5-氯-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷甲醯胺。二鹽酸鹽
向
化合物 10(100 mg，305.64 umol，1
eq)及4-溴-5-氯-1H-吲唑(84.90 mg，366.76 umol，1.2
eq)在二噁烷(3 mL)及H
2O(1 mL)的溶液中加入Na
2CO
3(97.18 mg，916.91 umol，3
eq)及Pd(dppf)Cl
2(11.18 mg，15.28 umol，0.05
eq)。將混合物在90°C下攪拌10小時。將混合物倒入石油醚(10 mL)中，用矽膠過濾，濾液在真空中濃縮。藉由prep-HPLC(柱：Phenomenex Synergi C18 150*25*10um；流動相：[水(0.05%HCl)-ACN]；B%：14%~34%，9分鐘)純化殘餘物，接著進行凍乾。獲得為白色固體
的實施例 223(36.8 mg，85.95μmol，28.12%產率，99.2%純度，2 HCl)。
1H NMR (400MHz, METHANOL-d
4) δ 8.92 (s, 1H), 8.13 (s, 1H), 7.99 - 7.91 (m, 3H), 7.68 (dd, J=1.0, 8.9 Hz, 1H), 7.58 (d, J=8.9 Hz, 1H), 1.95 - 1.87 (m, 1H), 1.12 - 1.07 (m, 2H), 1.05 - 0.98 (m, 2H); LCMS (電噴霧) m/z 352.0 (M+H)+。
合成方法
G
實施例231。N-(6-(5-溴-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-
基)環丙烷甲醯胺。2 TFA鹽
CuBr (137.29 mg, 957.04 umol, 29.15 uL, 1
eq) 與t-BuONO (98.69 mg, 957.04 umol, 113.83 uL, 1
eq) 在MeCN (5 mL) 中之混合物，於0°C下攪拌30分鐘，接著加入實施例227(662 mg，957.04 umol， 1
eq)在MeCN(1 mL)中的溶液，並將混合物在20°C下攪拌2小時，接著加入CuBr(137.29 mg，957.04 umol，29.15 uL，1 eq)和t-BuONO(98.69 mg，957.04 umol，113.83 uL，1 eq)，接著將混合物在20°C下再攪拌12小時。將反應混合物濃縮以得到殘餘物，接著將殘餘物溶解在乙酸乙酯(50 mL)中，接著用稀釋的氫氧化銨(3%，20mL*2)洗滌混合物，用鹽水(20mL)洗滌有機層，經Na
2SO
4乾燥，過濾並減壓濃縮，得到殘餘物。藉由prep-HPLC純化(柱：Phenomenex Synergi C18 150*25*10um；流動相：[水(0.1%TFA)-ACN]；B%：20%~50%，9分鐘)殘餘物。得到為黃色固體的
實施例 231(14mg，22.01umol，2.3%產率，2TFA)。
1H NMR (400MHz, DMSO-d
6) δ 13.49 (br s, 1H), 11.05 (s, 1H), 8.78 (s, 1H), 8.14 (s, 1H), 7.92 (s, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.57 (d, J=9.2 Hz, 1H), 7.32 (dd, J=1.7, 9.2 Hz, 1H), 2.05 - 1.86 (m, 1H), 0.85 - 0.79 (m, 4H); LCMS (electrospray) m/z 414.1 (M+H)+。
合成方法
H
實施例258。(1S,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-
基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺
步驟1)(1S,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1-(四氫-2H-吡喃-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺
向
中間體 1D(30 mg，78.06 umol，1 eq)及
化合物 11(32.33 mg，93.67 umol，1.2 eq)在二噁烷(1 mL)及H
2O(0.2 mL)中之溶液中加入Pd(dppf)Cl
2(5.71 mg，7.81 umol，0.1 eq)及Na
2CO
3(24.82 mg，234.17 umol，3 eq)，接著將混合物在80°C下在N
2下攪拌12小時。將反應混合物濃縮得到殘餘物。藉由prep-TLC(SiO
2，二氯甲烷：甲醇=10:1)純化殘餘物。得到為黃油狀的
化合物 12(34mg，57.44umol，73.59%產率，87%純度)。
步驟2)(1S,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺
向
化合物 12(34mg，57.44umol，1eq)在二噁烷(1 mL)的溶液中加入HCl/二噁烷(4M，1ml，69.64eq)，接著將混合物在20°C下在N
2下攪拌2小時。用乙酸乙酯(20 mL)稀釋反應混合物，並用飽和NaHCO
3水溶液(15 mL*2)洗滌混合物，經Na
2SO
4乾燥有機層，過濾並減壓濃縮，得到殘餘物。藉由prep-HPLC(柱：Phenomenex luna C18 150*25 10u；流動相：[水(0.1%TFA)-ACN]；B%：23%~53%，10分鐘)純化殘餘物。得到為白色固體的
實施例 258(8.7 mg，13.05μmol，22.72%產率，2 TFA)。
1H NMR (400 MHz, DMSO-d
6) δ 13.55 (br s, 1H), 11.21 (s, 1H), 8.80 (s, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.43 (d, J=9.2 Hz, 1H), 5.08 - 4.77 (m, 1H), 3.01 (s, 3H), 3.00 (s, 3H), 2.16 (td, J=7.0, 13.8 Hz, 1H), 1.76 - 1.57 (m, 1H), 1.27 - 1.11 (m, 1H); LCMS (電噴霧) m/z 431.2 (M+H)+。
合成方法
I
 |
步驟1)1-(4-溴-5-氯-6-氟-1-(四氫-2H-吡喃-2-基)-1H-吲唑-7-基)乙烷-1-酮
將
中間體 1A(3.29 g，9.86 mmol，1 eq)在THF(49 mL)溶液中冷卻至-78℃，接著將LDA(7.39 mL，14.7 mmol，1.5 eq)緩慢添加到反應混合物中，將混合物在相同溫度下攪拌30分鐘。接著逐滴添加酸酐(1.11 mL，11.8 mmol，1.2 eq)，並在室溫下攪拌反應混合物2小時。消耗中間體1A後，用水驟冷並用DCM萃取，分離，經無水MgSO
4乾燥，過濾，並在真空中濃縮。藉由矽膠色譜法純化殘餘物(產物在己烷/乙酸乙酯=10/1時產生)，得到為橙色固體的
化合物 13(1.86 g，4.95 mmol，50.2%產率)。
步驟2)1-(4-溴-5-氯-6-氟-1-(四氫-2H-吡喃-2-基)-1H-吲唑-7-基)乙烷-1-醇
將
化合物 13(1.86 mg，4.95 mmol，1 eq)在MeOH(24 mL)中的溶液冷卻至0°C，接著按比例添加硼氫化鈉(375 mg，9.90 mmol，2 eq)。將反應混合物在室溫下攪拌2小時。消耗
化合物 13後，濃縮反應混合物並用DCM萃取，用水洗滌，分離，經無水MgSO
4乾燥，過濾，並在真空中濃縮。藉由矽膠色譜法純化殘餘物(產物在己烷/乙酸乙酯=7/3時產生)，得到為象牙色固體的
化合物 14(615 mg，1.62 mmol，32%產率)。
步驟3)7-(1-(2H-四唑-2-基)乙基)-4-溴-5-氯-6-氟-1-(四氫-2H-吡喃-2-基)-1H吲唑
向
化合物 14(100 mg，0.265 mmol，1.0 eq)在THF(1.33 mL)中的溶液中加入1H四唑(0.89 mL，0.398 mmol，1.5 eq)和PPh3(104 mg，0.398 mmol，1.5 eq)。將混合物冷卻至0°C，並在0°C下緩慢加入DEAD(0.181 mL，0.398 mmol，1.5 eq)。將混合物在室溫下攪拌1小時。用DCM(30mL*3)萃取反應混合物。合併的有機層經Na
2SO
4乾燥，過濾，在真空中濃縮濾液。藉由矽膠色譜法(產物在己烷/乙酸乙酯=10/2時產生)純化粗產物，得到為白色固體的
化合物 15(62 mg，0.144 mmol，54%產率)。
步驟4)(1S，2S)-N-(6-(7-(1-(2H-四唑-2-基)乙基)-5-氯-6-氟-1-(四氫-2H-吡喃-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺
向
化合物 15(62 mg，0.144 mmol，1 eq)在1,4-二噁烷(0.577 mL)/H2O(0.144 mL)中的溶液中加入
化合物 11(54 mg，0.159 mmol，1.1 eq)、Pd(dppf)Cl
2(5 mg，0.007 mmol，0.05 eq)、Na
2CO
3(30 mg，0.289 mmol，2 eq)。將混合物脫氣並用氮氣清洗3次。將混合物在微波反應器中於120℃攪拌30分鐘。反應混合物藉由矽藻土過濾，濾液用DCM萃取。合併的有機層經Na
2SO
4乾燥，過濾，濾液在真空中濃縮，得到殘餘物。藉由矽膠色譜法純化殘餘物(產物在己烷/乙酸乙酯=2/8時產生)，得到為黃色固體的
化合物 16(68 mg，0.120 mmol，83%)。
步驟5)(1S，2S)-N-(6-(7-(1-(2H-四唑-2-基)乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺
向
化合物 16(66 mg，0.116 mmol，1 eq)在乙酸乙酯(0.6 mL)中的溶液中加入1 N HCl EA溶液(1.16 mL，1.16 mmol，10 eq)中。將混合物在室溫下攪拌1小時。反應混合物用飽和NaHCO
3驟冷，並用EA萃取，經Na
2SO
4乾燥，過濾，濾液在真空中濃縮。藉由矽膠色譜法純化粗產物(產物在DCM/MeOH=10/1時產生)，得到為象牙色固體的
實施例 393(4 mg，0.008 mmol，7%)。
1H NMR (400 MHz, DMSO-d
6) δ 13.77 (s, 1H), 11.07 (s, 1H), 8.99 (s, 1H), 8.80 (s, 1H), 8.14-8.04 (m, 2H), 7.58-7.54 (m, 1H), 7.35 (dd, J = 9.3, 1.6 Hz, 1H), 6.74 (q, J = 7.1 Hz, 1H), 5.00-4.79 (m, 1H), 2.23 (d, J = 7.2 Hz, 3H), 2.16-2.09 (m, 1H), 1.68-1.57 (m, 1H), 1.18-1.09 (m, 1H) ); LCMS (電噴霧) m/z 485.10 (M+H)+。
合成方法
J
實施例446。(1S,2S)-2-氟-N-(5-(5-甲基-1H-吲唑-4-基)吡唑[1,5-
a]吡啶-2-基)環丙烷甲醯胺
步驟1)(1S,2S)-N-(5-溴吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺
在N
2下於0°C下，向
化合物 17(3.1 g，14.62 mmol，1 eq)和(1S,2S)-2-氟環丙烷羧酸(1.67 g，16.08 mmol，1.1 eq)在CH
3CN(40 mL)中的混合物中緩慢加入MsCl(3.35 g，29.24 mmol，2.26 mL，2 eq)和3-甲基吡啶(6.81 g，73.10 mmol，7.12 mL，5 eq)。將混合物在30℃下攪拌3小時。減壓濃縮混合物。用乙酸乙酯(200 mL)溶解殘餘物，所得混合物用10%檸檬酸(30 mL*2)、飽和Na
2CO
3(30 mL*2)、鹽水(30 mL*2)洗滌，經Na
2SO
4乾燥，過濾並減壓濃縮，得到殘餘物。藉由矽膠層析法(1000g篩孔矽膠，石油醚/乙酸乙酯=5/1,3/1)純化殘餘物，得到為白色固體的
化合物 18(2.3 g，7.72 mmol，52.81%產率)。
步驟2)(1S,2S)-2-氟-N-(5-(4,4,5,5-四甲基-1,3,2-二氧苯甲醛-2-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺
將
化合物 18(0.345 g，1.159 mmol)、4,4,4',4',5,5,5,5', 5'-八甲基-2,2'-二(1,3,2-二氧苯甲醛，0.588 g，2.318 mmol)、[1,1'-二(二苯基膦基)二茂鐵]二氯鈀(II)(Pd(dppf)Cl
2，0.084 g，0.115 mmol)及醋酸鉀(0.398 g，4.056 mmol)在室溫下在DMSO(10 mL)中混合，接著將該混合物在90℃下攪拌18小時，冷卻至室溫，藉由矽藻土墊過濾以去除固體，並在乙酸乙酯與水之間分離。用飽和氯化鈉水溶液清洗有機層、分離，經無水硫酸鎂乾燥，過濾，真空濃縮。對殘餘物進行色層分析(SiO
2，12 g筒；乙酸乙酯/己烷=0%至100%)，得到為棕色固體的
化合物 19(0.289 g，72.3%)。
步驟3)(1S,2S)-2-氟-N-(5-(5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷甲醯胺
在N
2下，向
化合物 19(6 g*，17.34 mmol，1 eq)及4-溴-5-甲基-1H-吲唑(3.6 g，17.34 mmol，1 eq)在二噁烷(120 mL)及H
2O(24 mL)中的混合物中加入Na
2CO
3(3.67 g，34.68 mmol，2 eq)及Pd(dppf)Cl
2(1.28 g，1.73 mmol，0.1 eq)。將該混合物在90°C下攪拌4小時。減壓濃縮混合物，得到殘餘物。藉由矽膠色層分析法(1000篩孔矽膠，石油醚/乙酸乙酯=5/1,1/1、TLC(石油醚：乙酸乙酯=1:1；Rf=0.08)純化殘餘物，得到2.5 g黃色固體。該固體用CH
3CN(10 mL)研磨兩次。過濾混合物並收集過濾濾餅。用H
2O/CH
3CN(5:1；10 mL)分散濾餅，並將所得混合物凍乾第三次，得到為灰白色固體的
實施例 446(1.53 g，4.37 mmol，25.20%產率，96.98%純度)。
1H NMR (400 MHz, DMSO-d
6) δ 13.09 (s, 1H), 11.13 (s, 1H), 8.61 (d, J=7.1 Hz, 1H), 7.74 (s, 1H), 7.63 (d, J=0.9 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H), 7.32 (d, J=8.6 Hz, 1H), 6.91 (s, 1H), 6.86 (dd, J=1.9, 7.0 Hz, 1H), 5.06 - 4.98 (m, 1H), 4.88-4.84 (m, 1H), 2.34 (s, 3H), 2.15 (td, J=6.9, 13.8 Hz, 1H), 1.74 - 1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (電噴霧) m/z 350.1 (M+H)+。
下表1顯示實施例的化合物及用於製備化合物的一般合成方法及表徵數據。
表1.實施例化合物
| Ex # | 結構/名稱 | 1H NMR / MS (M+1) | 方法 |
| 1 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.04 (s, NH), 12.69 (s, CONH), 8.03 (s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.63 (s, 1H), 7.48-7.44 (m, 1H), 7.31 (d, J=8.4 Hz, 1H), 2.30 (s, 3H), 2.02 (t, J=5.6 Hz, 1H), 0.97 (t, J=4.0 Hz, 4H); LCMS (電灑) m/z 349.0 (M+H)+. | A |
| 2 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.04 (s, NH), 12.76 (s, CONH), 8.05 (s, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.63 (s, 2H), 7.49-7.44 (m, 2H), 7.31 (d, J=8.4 Hz, 1H), 5.05 (td, J12=3.3 Hz, J13=65.7 Hz, 1H), 2.24 (s, 3H), 2.23-2.24 (m, 1H), 1.78-1.73 (m, 1H), 1.31-1.23 (m, 1H); LCMS (電灑) m/z 367.1 (M+H)+. | A |
| 3 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.03 (s, 1H), 11.80 (s, 1H), 7.99 (s, 1H), 7.78 (d, 8.4 Hz, 1H), 7.63 (s, 1H), 7.46-7.42 (m, 2H), 7.31 (d, 8.4 Hz, 1H), 2.30 (s, 3H), 1.52 (s, 9H); LCMS (電灑) m/z 381.1 (M+H)+. | A |
| 4 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.02 (br s, 1H), 12.28 (br s, 1H), 8.04 (d, J=1.3 Hz, 1H), 7.83 (d, J=8.3 Hz, 1H), 7.63 (s, 1H), 7.50 - 7.43 (m, 2H), 7.31 (d, J=8.4 Hz, 1H), 3.44 (quin, J=8.5 Hz, 1H), 2.32-2.13 (m, 7H), 2.06-1.92 (m, 1H), 1.90 - 1.78 (m, 1H); LCMS (電灑) m/z 363.2 (M+H)+. | A |
| 5 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.21 - 12.83 (m, 2H), 8.08 (d, J=1.2 Hz, 1H), 7.89 (d, J=8.3 Hz, 1H), 7.64 (s, 1H), 7.52 - 7.43 (m, 2H), 7.32 (d, J=8.6 Hz, 1H), 3.02 (td, J=9.5, 13.0 Hz, 1H), 2.30 (s, 3H), 2.23 - 2.11 (m, 2H) ; LCMS (電灑) m/z 385.0 (M+H)+. | A |
| 6 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.05 (br s, 1H), 12.50 (s, 1H), 8.06 (d, J=1.3 Hz, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.63 (s, 1H), 7.50 - 7.44 (m, 2H), 7.32 (d, J=8.6 Hz, 1H), 5.19 - 4.95 (m, 1H), 2.97 - 2.85 (m, 1H), 2.66 - 2.57 (m, 2H), 2.45 - 2.35 (m, 2H), 2.30 (s, 3H) ; LCMS (電灑) m/z 381.1 (M+H)+. | A |
| 7 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.03 (br s, 1H), 12.48 (s, 1H), 8.06 (d, J=1.3 Hz, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.63 (s, 1H), 7.50 - 7.43 (m, 2H), 7.32 (d, J=8.6 Hz, 1H), 5.37 - 5.15 (m, 1H), 3.45 (br d, J=3.1 Hz, 1H), 2.65 - 2.55 (m, 2H), 2.45-2.35 (m, 2H), 2.30 (s, 3H); LCMS (電灑) m/z 381.1 (M+H)+. | A |
| 8 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.04(s, 1H), 12.93(s, 1H), 8.16(dd, J=8.4 Hz, J=2.0 Hz, 2H), 8.10(s, 1H), 7.91(d, J=7.6 Hz, 1H), 7.70-7.65(m, 2H), 7.60-7.57(m, 2H), 7.53(dd, J=8.4 Hz, 2.0 Hz, 1H), 7.47(d, J=8.4 Hz, 1H), 7.32(d, J=8.8 Hz, 1H), 2.32(s, 3H) ; LCMS (電灑) m/z 385.1 (M+H)+. | A |
| 9 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.99 (s, NH), 12.31 (s, NH), 7.99 (s, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.58 (s, 1H), 7.44-7.40 (m, 2H), 7.27 (d, J = 8.0 Hz, 1H), 2.26 (s, 3H), 1.59 (m, 2H), 1.31-1.29 (m, 2H), 0.89-0.85 (m, 3H); LCMS (電灑) m/z 365.1 (M+H)+. | A |
| 10 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.98 (s, NH), 12.32 (s, NH), 7.99 (s, 1H), 7.80 (d, J = 8.0 Hz, 1H), 7.58 (s, 1H), 7.44-7.40 (m, 2H), 7.27 (d, J = 8.0 Hz, 1H), 2.96 (m, 1H), 2.26 (s, 3H), 1.89 (m, 2H), 1.79-1.49 (m, 4H), 1.24-1.20 (m, 1H), 0.83-0.80 (m, 1H); LCMS (電灑) m/z 377.1 (M+H)+. | A |
| 11 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.08 (br s, 1H), 12.60 (br s, 1H), 8.07 (d, J=1.3 Hz, 1H), 7.86 (d, J=8.2 Hz, 1H), 7.64 (s, 1H), 7.51 - 7.43 (m, 2H), 7.32 (d, J=8.6 Hz, 1H), 3.38 - 3.25 (m, 1H), 2.98 - 2.81 (m, 4H), 2.30 (s, 3H); LCMS (電灑) m/z 377.1 (M+H)+. | A |
| 12 |  | 1H NMR (400 MHz, DMSO-d 6) d 13.00 (s, 1H), 12.17 (s, 1H), 8.82 (d, J = 4.4 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 8.16 ~ 8.12 (m, 2H), 7.93 (d, J = 8.8 Hz, 1H), 7.76 (dd, J = 7.2, 4.8 Hz, 1H), 7.64 (s, 1H), 7.52 (dd, J = 8.4, 1.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 2.32 (s, 3H); LCMS (電灑) m/z 386.1 (M+H)+. | A |
| 13 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.31(s, 1H), 12.74(brs, 1H), 8.43(s, 1H), 7.93(d, J=1.6 Hz, 1H), 7.73(d, J=2.4 Hz, 1H), 7.71(s, 1H), 7.60(d, J=3.2 Hz, 2H), 7.36-7.34(m, 1H), 7.31(dd, J=8.4 Hz, J=1.2 Hz, 1H), 6.92-6.89(m, 1H), 6.86-6.85(m, 1H), 2.03-1.98(m, 1H), 0.99-0.95(m, 4H); LCMS (電灑) m/z 417.0 (M+H)+. | B |
| 14 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.07(s, 1H), 12.62(s, 1H), 8.25(s, 1H), 8.08(s, 1H), 8.03(s, 1H), 7.77-7.67(m, 3H), 7.59(d, J=8.0 Hz, 1H), 2.00-1.96(m, 1H), 0.96-0.92(m, 4H) ; LCMS (電灑) m/z 335.1 (M+H)+. | A |
| 15 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.27(s, 1H), 12.69(s, 1H), 8.21(s, 1H), 8.00(s, 1H), 7.84(d, J=8.4 Hz, 1H), 7.65(dd, J=8.4 Hz, J=1.6 Hz, 1H), 7.54(dd, J=10.8 Hz, J=9.2 Hz, 1H), 2.02-1.96(m, 1H), 0.95-0.93(m, 4H); LCMS (電灑) m/z 353.1 (M+H)+. | B |
| 16 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38(s, 1H), 12.74(s, 1H), 8.09(d, J=1.6 Hz, 1H), 7.83(d, J=8.8 Hz, 1H), 7.72(s, 1H), 7.55(d, J=8.8 Hz, 1H), 7.51(dd, J=8.4 Hz, J=1.6 Hz, 1H), 7.46(d, J=8.8 Hz, 1H), 2.02-1.97(m, 1H), 0.97-0.93(m, 4H); LCMS (電灑) m/z 369.0 (M+H)+. | B |
| 17 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.58(s, 1H), 12.74(s, 1H), 8.03(d, J=1.6 Hz, 1H), 7.84(d, J=8.0 Hz, 1H), 7.75(s, 2H), 7.71(s, 1H), 7.44(dd, J=8.8 Hz, 1.6 Hz, 1H), 20.4-2.00(m, 1H), 0.99-0.96(m, 4H); LCMS (電灑) m/z 403.0 (M+H)+. | B |
| 18 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.19(s, 1H), 12.64(s, 1H), 7.84(s, 1H), 7.75(s, 1H), 7.65(d, J=8.0 Hz, 1H), 7.55(d, J=8.0 Hz, 1H), 7.48(d, J=8.0 Hz, 1H), 7.29-7.20(m, 3H), 6.63(d, J=4.0 Hz, 1H), 3.66-3.62(m, 1H), 2.01-1.92(m, 1H), 0.98-0.85(m, 4H); LCMS (電灑) m/z 417.1 (M+H)+. | B |
| 19 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.75(s, 1H), 12.71(s, 1H), 8.35(s, 2H), 7.86(d, J=6.8 Hz, 1H), 7.79(s, 1H), 7.53(d, J=6.8 Hz, 1H), 7.28(d, J=6.0 Hz, 1H), 2.05-1.95(m, 1H), 1.10-0.90(m, 4H); LCMS (電灑) m/z 369.0 (M+H)+. | B |
| 20 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36(s, 1H), 12.73(s, 1H), 8.39(s, 1H), 8.27(s, 1H), 7.88-7.81(m, 2H), 7.62(s, 1H), 7.31(s, 1H), 2.04-1.99(m, 1H), 0.99-0.97(m, 4H); LCMS (電灑) m/z 369.0 (M+H)+. | B |
| 21 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (s, NH), 12.70(s, NH), 7.95 (s, 1H), 7.84-7.82 (m, 2H), 7.75 (d, J=8.4 Hz, 1H), 7.60(d, J=9.6 Hz, 1H), 7.44(d, J=10.0 Hz, 1H), 2.02-1.98(m, 1H), 1.08 (s, 9 H), 0.98-0.96 (m, 4H); LCMS (電灑) m/z 435.1 (M+H)+. | B |
| 22 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.28(s, 1H), 12.74(s, 1H), 8.43(s, 1H), 8.23(s, 1H), 7.88-7.87(m, 2H), 7.72-7.71(m, 2H), 7.61-7.59(m, 2H), 7.19(dd, J=5.2 Hz, J=3.2 Hz, 1H), 2.07-2.00(m, 1H), 1.01-0.97(m, 4H); LCMS (電灑) m/z 417.0 (M+H)+. | B |
| 23 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.31 (s, NH), 12.71 (s, NH), 8.45-8.42 (m, 1H), 8.02 (s, 1H), 7.90 (s, 1H), 7.72-7.70 (d, J = 8.0 Hz, 1H), 7.48-7.50 (d, J = 8.4 Hz, 1H), 7.46 (m, 4H), 6.76 (m, 1H), 4.24 (d, J = 5.2 Hz, 1H), 2.03-2.01 (m, 1H), 0.99-0.97 (m, 4H); LCMS (電灑) m/z 474.1 (M+H)+. | B |
| 24 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.03(s, 1H), 12.67(s, 1H), 8.11(d, J=3.2 Hz, 1H), 7.82-7.80(m, 2H), 7.60(dd, J=8.4 Hz, J=1.6 Hz, 1H), 7.53(d, J=9.2 Hz, 1H), 7.34(d, J=8.4 Hz, 1H), 3.75(s, 3H), 2.05-1.98(m, 1H), 0.98-0.96(m, 4H); LCMS (電灑) m/z 365.1 (M+H)+. | B |
| 25 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.13(s, 1H), 12.72(s, 1H), 8.07(d, J=1.6 Hz, 1H), 7.84(d, J=8.0 Hz, 1H), 7.71(s, 1H), 7.58-7.53(m, 3H), 5.15-5.08(m, 1H), 4.45(d, J=5.2 Hz, 2H), 2.04-1.99(m, 1H), 1.02-0.96(m, 4H); LCMS (電灑) m/z 365.0 (M+H)+. | B |
| 26 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.03 (s, NH), 12.77 (s, NH), 7.97 (s, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.49-7.38 (m, 3H), 4.20 (br, NH2), 2.10 (m, 1H), 1.99 (s, 3H), 0.99-0.96 (m, 4H); LCMS (電灑) m/z 364.1 (M+H)+. | B |
| 27 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.85 (s, 1H), 12.61 (s, 1H), 9.02 (s, 1H), 8.11 (s, 1H), 7.77 - 7.75 (m, 2H), 7.65 (d, J=9.2 Hz, 1H), 7.34 (d, J=8.6 Hz, 1H), 7.07 (d, J=8.6 Hz, 1H), 1.97 (quin, J=6.2 Hz, 1H), 0.94 (d, J=6.0 Hz, 4H); LCMS (電灑) m/z 351.40 (M+H)+. | B |
| 28 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.04(s, 1H), 12.69(s, 1H), 7.99(d, J=1.2 Hz, 1H), 7.84(d, J=8.4 Hz, 1H), 7.55(s, 1H), 7.50(d, J=8.4 Hz, 1H), 7.42(dd, J=7.6 Hz, 1.6 Hz, 1H), 7.35(d, J=9.2 Hz, 1H), 2.0(q, J=7.6 Hz, 2H), 2.05-1.99(m, 1H), 1.08(t, J=7.6 Hz, 3H), 0.98-0.96(m, 4H); LCMS (電灑) m/z 363.1 (M+H)+. | B |
| 29 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.68(s, 1H), 12.76(s, 1H), 8.28(d, J=1.6 Hz, 1H), 8.07(s, 1H), 7.89(d, J=8.4 Hz, 1H), 7.75(d, J=9.2 Hz, 1H), 7.69(dd, J=8.4 Hz, J=1.6 Hz, 2H), 2.03-1.96(m, 1H), 0.96-0.94(m, 4H) ; LCMS: m/z =403.0 (M+H+)LCMS (電灑) m/z 360.1 (M+H)+. | B |
| 30 |  | 1H NMR (400 MHz, DMSO-d 6) 13.37(s, 1H), 12.76(s, 1H), 8.15(d, J=1.6 Hz, 1H), 7.88(d, J=8.4 Hz, 1H), 7.77(brs, 1H), 7.60-7.55(m, 2H), 7.50(d, J=9.2 Hz, 1H), 5.16-4.95(m, 1H), 2.28-2.21(m, 1H), 1.81-1.71(m, 1H), 1.38-1.28(m, 1H) ; LCMS (電灑) m/z 387.0 (M+H)+. | B |
| 31 |  | 1H NMR (400 MHz, DMSO-d 6) 12.85(s, 1H), 12.76(s, 1H), 8.19 (s, 1H), 7.81 - 7.78 (m, 2H), 7.68 (d, J=9.2 Hz, 1H), 7.56 (d, J=8.6 Hz, 1H), 7.34 (d, J=8.6 Hz, 1H), 5.16-4.95 (m, 1H), 4.26 (t, J=4.4 Hz, 2H), 3.32 (t, J=4.4 Hz, 2H), 2.45 (s, 6H), 2.28 - 2.21(m, 1H), 1.78 -1.68 (m, 1H), 1.38-1.28(m, 1H) ; LCMS (電灑) m/z 440.10 (M+H)+. | B |
| 32 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.14 (s, NH), 13.08 (s, NH), 8.12 (s, 1H), 7.94-7.92 (m, 1H), 7.65 (s, 1H), 7.55 (dd, J12=1.6 Hz, J13=8.4 Hz, 1H), 7.47 (d, J=8.4 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 2.75 (m, 1H), 2.31 (s, 3H), 1.21-1.17 (m, 4H); LCMS (電灑) m/z 365.0 (M+H)+. | A |
| 33 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.50(s, 1H), 12.85(s, 1H), 8.11(s, 1H), 7.91(d, J=8.4 Hz, 2H), 7.85(s, 1H), 7.72(d, J=4.0 Hz, 2H), 7.50(d, J=8.8 Hz, 1H), 6.82(t, J=55.2 Hz, 1H), 5.14-4.98(m, 1H), 2.25-2.22(m, 1H), 1.82-1.72(m, 1H), 1.37-1.30(m, 1H) ; 19F NMR (400MHz, DMSO-d6) δ -102.50(d, J=56.8 Hz, 1H), -103.08(d, J=56.8 Hz, 1H), 219.66-219.92(m, 1H) ; LCMS (電灑) m/z = 403.0 (M+H+) | B |
| 34 |  | 1H NMR (400 MHz, DMSO-d 6) 12.85(s, 1H), 12.77(s, 1H), 8.21 (s, 1H), 7.86 (s, 1H), 7.83 (d, J=8.4 Hz, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.32 (d, J=9.2 Hz, 1H), 5.13-4.96 (m, 1H), 4.08 (t, J=4.6 Hz, 2H), 3.53 (t, J=4.4 Hz, 2H), 3.21 (s, 3H), 2.29 - 2.22(m, 1H), 1.80 -1.70 (m, 1H), 1.36-1.27(m, 1H) ; LCMS (電灑) m/z 427.10 (M+H)+. | B |
| 35 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.22(s, 1H), 12.78(s, 1H), 8.02(d, J=1.6 Hz, 1H), 7.86(d, J=8.0 Hz, 1H), 7.77(d, J=8.8 Hz, 1H), 7.70(s, 1H), 7.55(d, J=8.8 Hz, 1H), 7.43(dd, J=8.4 Hz, J=2.0 Hz, 1H), 6.69(dd, J=17.6 Hz, J=10.8 Hz, 1H), 5.76(d, J=16.4 Hz, 1H), 5.16(d, J=12.0 hz, 1H), 5.13-4.94(m, 1H), 2.24-2.20(m, 1H), 1.72-1.71(m, 1H), 1.35-1.28(m, 1H); LCMS (電灑) m/z =379.1 (M+H+) | B |
| 36 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.77(s, 1H), 8.13(dd, J=4.4 Hz, 1.6 Hz, 1H), 7.92(dd, J=8.4 Hz, 6.4 Hz, 1H), 7.88(d, J=7.6 Hz, 1H), 7.64-7.54(m, 3H), 5.10-4.92(m, 1H), 5.39-5.27(m, 1H), 4.73-4.60(m, 1H), 2.22-2.21(m, 1H), 1.69-1.68(m, 1H), 1.30-1.25(m, 1H); LCMS (電灑) m/z =383.1. (M+H+) | B |
| 37 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.01(s, 1H), 12.74(s, 1H), 8.07(s, 1H), 7.83(dd, J=8.4 Hz, 1H), 7.58(s, 1H), 7.51(d, J=8.0 Hz, 1H), 7.41(d, J=8.8 Hz, 1H), 6.95(dd, J=8.4 Hz, 1.2 Hz, 1H), 5.10-4.92(m, 1H), 2.21-2.17(m, 1H), 1.94-1.90(m, 1H), 1.74-1.69(m, 1H), 1.30-1.11(m, 1H), 0.82-0.75(m, 1H), 0.60-0.59(m, 1H); LCMS (電灑) m/z =393.1 (M+H+) | B |
| 38 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.79(s, 1H), 8.06(d, J=2.0 Hz, 1H), 7.84(d, J=8.0 Hz, 1H), 7.67(s, 1H), 7.55-7.53(m, 2H), 7.48(d, J=8.8 Hz, 1H), 7.39(d, J=1.2 Hz, 1H), 7.16(d, J=8.8 Hz, 1H), 6.18-6.17(m, 1H), 5.29(s, 2H), 5.10-4.93(m, 1H), 2.23-2.20(m, 1H), 1.76-1.68(m, 1H), 1.31-1.27(m, 1H); LCMS (電灑) m/z =433.1 (M+H+) | B |
| 39 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.35(s, 1H), 12.77(s, 1H), 8.20(d, J=2.0 Hz, 1H), 7.87(s, 1H), 7.83(d, J=8.4 Hz, 1H), 7.66(dd, J=8.4 Hz, 1.6 Hz, 1H), 7.51(d, J=3.2 Hz, 1H), 5.12-4.91(m, 1H), 3.91(s, 1H), 2.21-2.18(m, 1H), 1.75-1.68(m, 1H), 1.29-1.23(m, 1H); LCMS (電灑) m/z =377.1 (M+H+) | B |
| 40 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (s, NH), 12.80 (s, NH), 8.09 (s, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.35 (d, J=9.6 Hz, 1H), 4.96-5.15 (m, 1H), 2.25-2.22 (m, 1H), 2.18 (s, 3H), 1.79-1.72 (m, 1H), 1.33-1.31 (m, 1H); LCMS (電灑) m/z 385.1 (M+H)+. | B |
| 41 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (s, NH), 12.80 (s, NH), 8.09 (s, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.67 (s, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.35 (d, J=9.6 Hz, 1H), 4.96-5.15 (m, 1H), 2.25-2.22 (m, 1H), 2.18 (s, 3H), 1.79-1.72 (m, 1H), 1.33-1.31 (m, 1H); LCMS (電灑) m/z 385.1 (M+H)+. | B |
| 42 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.46 (s, NH), 12.83 (s, NH), 8.19 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.80 (s, 1H), 7.64 (d, J = 8.8 Hz, 1H), 5.16-4.95 (m, 1H), 2.28-2.21 (m, 1H), 1.79-1.72 (m, 1H), 1.35-1.28 (m, 1H); LCMS (電灑) m/z =405.0 (M+H+) | B |
| 43 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.59 (s, NH), 12.79 (s, NH), 8.05 (s, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.71 s, 1H), 7.46-7.40 (m, 2H), 6.48 (dd, J12=11.8 Hz, J13=17.8 Hz, 1H), 5.35 (dd, J12=2.6 Hz, J13=14.2 Hz, 1H), 5.16-4.95 (m, 1H), 2.26-2.21 (m, 1H), 1.79-1.72 (m, 1H), 1.35-1.29 (m, 1H); LCMS (電灑) m/z 449.0 (M+H)+. | B |
| 44 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.34 (s, 1H), 12.77 (d, J=3.2Hz, 1H), 7.88 (d, J=1.6Hz, 1H), 7.80 (d, J=8.4Hz, 1H), 7.38 (d, J=9.6Hz, 1H), 7.30 (dd, J=2.0, 6.4Hz, 1H), 5.10 (m, 0.5H), 4.93 (m, 0.5H), 2.20 (m, 1H), 2.00 (m, 3H), 1.71 (m, 1H), 1.28 (m, 1H) , LCMS (電灑) m/z 419.05 (M+H)+. | B |
| 45 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.55 (s, 1H), 12.79 (d, J=3.6Hz, 1H), 7.87 (d, J=2.0Hz, 1H), 7.86 (d, J=7.6Hz, 1H), 7.41 (d, J=10.0Hz, 1H), 7.28 (dd, J=1.6Hz, 1H), 5.14 (m, 0.5H), 4.97 (m, 0.5H), 2.23 (m, 1H), 2.00 (m, 3H), 1.76 (m, 1H), 1.31 (m, 1H), LCMS (電灑) m/z 511.00 (M+H)+. | B |
| 46 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (s, NH), 12.80 (s, NH), 8.04 (s, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.56 (s, 1H), 7.44 (d, J=8.4 Hz, 1H), 5.15-4.96 (m, 1H), 2.58-2.54 (m, 2H), 2.25-2.22 (m, 1H), 1.78-1.72 (m, 1H), 1.33-1.30 (m, 1H), 1.06 (t, 3H); LCMS (電灑) m/z 399.1 (M+H)+. | B |
| 47 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.41(s, 1H), 12.78(s, 1H), 8.23(d, J=1.6 Hz, 1H), 7.89(s, 1H), 7.84(d, J=8.4 Hz, 1H), 7.67(d, J=8.4 Hz, 1H), 7.46(d, J=9.6 Hz, 1H), 5.11-4.92(m, 1H), 4.19(s, 1H), 2.21-2.18(m, 1H), 1.77-1.67(m, 1H), 1.33-1.25(m, 1H); LCMS (電灑) m/z 395.1 (M+H+) | B |
| 48 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.34(s, 1H), 12.77(s, 1H), 8.01(d, J=2.0 Hz, 1H), 7.84(d, J=8.4 Hz, 1H), 7.60(s, 1H), 7.45(d, J=8.4 Hz, 1H), 7.41(dd, J=8.4 Hz, J=1.2 Hz, 1H), 5.12-4.92(m, 1H), 2.21-2.19(m, 1H), 1.76-1.69(m, 1H), 1.31-1.26(m, 1H); LCMS (電灑) m/z 497.0 (M+H+) | B |
| 49 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (s, 1H), 12.78 (d, J=3.6Hz, 1H), 7.89 (d, J=1.6Hz, 1H), 7.84 (d, J=8.4Hz, 1H), 7.43 (d, J=10Hz, 1H), 7.31 (dd, J=1.6, 6.8Hz, 1H), 5.14 (m, 0.5H), 4.95 (m, 0.5H), 2.24 (m, 1H), 2.02 (t, J=2.4Hz, 3H), 1.75 (m, 1H), 1.31 (m, 1H); LCMS (電灑) m/z 464.00 (M+H)+. | B |
| 50 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.67(s, 1H), 12.82(s, 1H), 8.03(s, 1H), 7.82(d, J=8.4 Hz, 1H), 7.66-7.64(m, 1H), 7.41(d, J=8.4 Hz, 1H), 5.15-4.95(m, 1H), 2.26-2.23(m, 1H), 1.79-1.72(m, 1H), 1.34-1.28(m, 1H); LCMS (電灑) LCMS: m/z 439.1 (M+H+) | B |
| 51 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.75 (s, 1H), 12.82 (s, 1H), 8.09 (d, J=1.6Hz, 1H), 7.88 (d, J=8.4Hz, 1H), 7.79 (brs, 1H), 7.50 (dd, J=1.6, 6.4Hz, 1H), 5.14 (m, 0.5H), 4.97 (m, 0.5H), 2.23 (m, 4H), 1.76 (m, 1H), 1.32 (m, 1H); LCMS (電灑) m/z 419.00 (M+H)+. | B |
| 52 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.16 (s, 1H), 12.81 (s, 1H), 7.91 (d, J=1.6Hz, 1H), 7.87 (d, J=8.4Hz, 1H), 7.33 (m, 2H), 5.73 (m, 1H), 5.59 (m, 1H), 5.14 (m, 0.5H), 4.97 (m, 0.5H), 4.84 (m, 1H), 2.25 (m, 1H), 2.01 (t, J=2.4Hz, 3H) 1.76 (m, 1H), 1.32 (m, 1H); LCMS (電灑) m/z 411.10 (M+H)+. | B |
| 53 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.00(s, 1H), 12.80(s, 1H), 7.92(d, J=1.2 Hz, 1H), 7.84(d, J=8.4 Hz, 1H), 7.34(dd, J=8.4 Hz, J=1.6 Hz, 1H), 5.15-4.97(m, 1H), 2.26-2.24(m, 1H), 2.08(s, 3H), 1.79-1.76(m, 1H), 1.32-1.27(m, 1H); LCMS (電灑) m/z 454.0 (M+H+) | B |
| 54 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.03(s, 1H), 13.21(s, 1H), 7.94(d, J=1.6 Hz, 1H), 7.50(d, J=1.6 Hz, 1H), 5.14-4.95(m, 1H), 2.25-2.22(m, 1H), 2.09(s, 3H), 1.80-1.70(m, 1H), 1.36-1.29(m, 1H); LCMS (電灑) m/z 487.0 (M+H+) | B |
| 55 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.33(s, 1H), 12.80(s, 1H), 8.06(s, 1H), 7.84(d, J=8.0 Hz, 1H), 7.43-7.41(m, 1H), 5.13-4.97(m, 1H), 2.23-2.20(m, 1H), 2.16(s, 3H), 1.77-1.72(m, 1H), 1.44-1.41(m, 1H); LCMS (電灑): m/z 421.0 (M+H+) | B |
| 56 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.78 (s, 1H), 12.60 (s, 1H), 8.09 (s, 1H), 8.06 (s, 1H), 7.84 (d, J=8.0 Hz, 1H), 7.43-7.41 (m, 1H), 5.13-4.97 (m, 1H), 2.23-2.20 (m, 1H), 2.16 (s, 3H), 1.77-1.72 (m, 1H), 1.44-1.41 (m, 1H); LCMS (電灑): m/z 403.0 (M+H)+. | B |
| 57 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.59 (s, 1H), 12.81 (s, 1H), 8.15 (s, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.82 (s, 1H), 7.34 (dd, J=8.4 Hz, J=1.6 Hz, 1H), 5.18-5.12 (m, 0.5H), 5.01-4.96 (m, 0.5H), 2.50 (t, J=1.6 Hz, 3H), 2.29-2.21 (m, 1H), 1.85-1.72 (m, 1H), 1.38-1.29 (m, 1H); LCMS (電灑) m/z 419.0 (M+H)+. | B |
| 58 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.76 (br s, 1H), 12.82 (br s, 1H), 8.19 (d, J=1.7 Hz, 1H), 7.96 - 7.82 (m, 2H), 7.59 (dd, J=1.8, 8.4 Hz, 1H), 5.26 - 4.85 (m, 1H), 2.57 (s, 3H), 2.30 - 2.19 (m, 1H), 1.84 - 1.69 (m, 1H), 1.33 (tdd, J=6.4, 9.0, 12.9 Hz, 1H); LCMS (電灑) m/z 450.8 (M+H)+. | B |
| 59 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36 (s, 1H), 12.77 (br s, 1H), 8.04 (s, 1H), 7.87 (dd, J12= 4.8 Hz, J13=8.4 Hz, 1H), 7.66 (s, 1H), 7.45 (d, J=7,6 Hz, 1H), 5.14 - 4.95 (m, 1H), 2.49 (d, J=1.7 Hz, 3H), 2.21 (d, J=2.8 Hz, 3H), 2.18 - 2.10 (m, 1H), 1.75 - 1.61 (m, 1H), 1.27 - 1.10 (m, 1H); LCMS (電灑) m/z 399.1 (M+H)+. | B |
| 60 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.87 (s, 1H), 12.85 (s, 1H), 8.22 (s, 1H), 7.88 (m, 2H), 7.60 (dd, J12=1.8 Hz, J13=8.2 Hz, 1H), 5.13-4.97 (m, 1H), 2.28-2.21 (m, 1H), 1.95 (s, 3H), 1.92 (s, 3H), 1.81-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS (電灑) m/z 481.1 (M+H)+. | B |
| 61 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 (s, 1H), 12.82 (s, 1H), 8.19 (d, J=2.0Hz, 1H), 7.90 (d, J=8.4 Hz, 2H), 7.59 (dd, J=6.8 Hz, J=2.0 Hz, 1H), 7.10 (q, J=12.4 Hz, 1H), 6.22 (brs, 1H), 5.81 (d, J=11.6 Hz, 1H), 5.16-5.12 (m, 0.5H), 4.99-4.96 (m, 0.5H), 2.28-2.21 (m, 1H), 1.81-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS (電灑) m/z 431.0 (M+H)+. | B |
| 62 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.37 (s, 1H), 12.79 (s, 1H), 8.08 (s, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.11-7.09 (m, 1H), 6.16 (d, J=18.4 Hz, 1H), 5.70 (d, J=12.0 Hz, 1H), 5.14-4.97 (m, 1H), 2.28-2.21 (m, 1H), 2.20 (s, 3H), 1.81-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS (電灑) m/z 411.1 (M+H)+. | B |
| 63 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.85 (s, 1H), 8.22 (s, 1H), 7.96-7.89 (m, 2H), 7.49 (d, J=8.0 Hz, 1H), 7.11-7.09 (m, 1H), 7.60 (d, J=8.0 Hz, 1H), 5.14-4.97 (m, 1H), 3.19 (s, 3H), 2.28-2.21 (m, 1H), 1.79-1.73 (m, 1H), 1.37-1.28 (m, 1H); LCMS (電灑) m/z 467.0 (M+H)+. | B |
| 64 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.79 (br s, 1H), 8.08 (s, 1H), 7.87 (d, J=8.0 Hz, 1H), 7.73 (s, 1H), 7.49 (d, J=9.6 Hz, 1H), 5.14 - 4.96 (m, 1H), 3.17 (s, 3H), 2.54 (s, 3H), 2.16 (td, J=6.9, 13.8 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS (電灑) m/z 431.0 (M+H)+. | B |
| 65 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.44 - 8.32 (m, 2H), 7.84 - 7.76 (m, 1H), 7.42 - 7.25 (m, 5H), 5.07 - 5.01 (m, 1H), 3.27 - 2.97 (m, 5H), 2.24 - 2.15 (m, 1H), 2.06 (br d, J = 2.2 Hz, 3H), 1.96 - 1.81 (m, 1H), 1.38 - 1.28 (m, 1H); LCMS (電灑) m/z 490.2 (M+H)+. | B |
| 66 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36 (br s, 1H), 12.81 (s, 1H), 8.12 (s, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 5.14 - 4.96 (m, 1H), 3.13 (s, 3H), 2.32 (s, 3H), 2.16 (td, J=6.9, 13.8 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS (電灑) m/z 447.1 (M+H)+. | B |
| 67 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.35 (s, 1H), 12.79 (s, 1H), 8.08 (s, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.83 (br s, 1H), 7.48 (dd, J=1.6, 6.8 Hz, 1H), 5.14 - 4.96 (m, 1H), 2.26 - 2.18 (m, 4H), 1.82 - 1.71 (m, 1H), 1.36 - 1.28 (m, 1H); LCMS (電灑) m/z 511.00 (M+H)+. | B |
| 68 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.94 (s, 1H), 12.76 (s, 1H), 8.08 (d, J=1.6 Hz, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.71 (s, 1H), 7.52 (dd, J=2.4, 6.4 Hz, 1H), 5.69 (s, 2H), 5.16 - 4.94 (m, 1H), 2.27 - 2.20 (m, 1H), 1.81 - 1.70 (m, 1H), 1.36 - 1.27 (m, 1H); LCMS (電灑) m/z 420.00 (M+H)+. | B |
| 69 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (s, 1H), 12.79 (s, 1H), 8.13 (d, J=1.6 Hz, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.76 (s, 1H), 7.55 (dd, J=1.6, 6.8 Hz, 1H), 5.16 - 4.95 (m, 1H), 2.99 (s, 6H), 2.28 - 2.21 (m, 1H), 1.81 - 1.71 (m, 1H), 1.36 - 1.28 (m, 1H); LCMS (電灑) m/z 448.10 (M+H)+. | B |
| 70 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 (br s, 1H), 12.81 (s, 1H), 8.15 (s, 1H), 7.96 (br s, 2H), 7.90-7.86 (m, 2H), 7.55 (d, J=8.4 Hz, 1H), 5.11 - 4.92 (m, 1H), 3.14 (m, 2H), 2.88 (m, 2H), 2.16 (td, J=6.9, 13.8 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS (電灑) m/z 480.1 (M+H)+. | B |
| 71 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.76 (s, 1H), 12.82 (s, 1H), 8.17 (d, J=0.8 Hz, 1H), 7.88 (s, 1H), 7.86 (d, J=8.4 Hz, 1H), 7.58 (dd, J=1.6, 6.8 Hz, 1H), 5.14 - 4.94 (m, 1H), 3.50 (t, J=6.0 Hz, 2H), 3.20 (s, 3H), 3.17 (t, J=6.4 Hz, 2H), 2.26 - 2.19 (m, 1H), 1.80 - 1.70 (m, 1H), 1.35 - 1.26 (m, 1H); LCMS (電灑) m/z 495.10 (M+H)+. | B |
| 72 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.29 (s, 1H), 10.42 (s, 1H), 7.80 (s, 1H), 7.75 (d, J=1.6 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.31 (dd, J=1.6, 6.8 Hz, 1H), 6.58 (q, J=10 Hz, 1H), 6.32 (dd, J=1.6, 15.2 HZ, 1H), 5.83 (d, J=10 Hz, 1H), 4.86 - 4.65 (m, 1H), 1.95 (d, J=14 Hz, 1H), 1.85 (m, 1H), 1.69 - 1.55 (m, 1H), 0.95 - 0.87 (m, 1H); LCMS (電灑) m/z 474.00 (M+H)+. | B |
| 73 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.78 (br s, 1H), 12.81 (s, 1H), 8.18 (s, 1H), 7.99 (t, J=5.2 Hz, 1H), 7.89 - 7.87 (m, 2H), 7.59 (d, J=8.4 Hz, 1H), 5.13 - 4.96 (m, 1H), 3.29 (m, 2H), 3.00 (m, 2H), 2.16 (td, J=6.9, 13.8 Hz, 1H), 1.75 (s, 3H), 1.74 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS (電灑) m/z 522.1 (M+H)+. | B |
| 74 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.50 (br s, 1H), 12.82 (s, 1H), 8.14 (s, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.81 (s, 1H), 7.55 (d, J=8.4 Hz, 1H), 5.14 - 4.76 (m, 1H), 3.83 (m, 4H), 3.28 (m, 4H), 2.16 (td, J=6.9, 13.8 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS (電灑) m/z 490.1 (M+H)+. | B |
| 75 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.60 (s, 1H), 12.82 (s, 1H), 8.13 (s, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.84 (s, 1H), 7.54 (d, J=8.4 Hz, 1H), 5.16 - 4.97 (m, 1H), 3.55 (br s, 6H), 3.39 (br s, 2H), 2.90 (d, J=8.0 Hz, 3H), 2.19 - 2.10 (m, 1H), 1.73 - 1.60 (m, 1H), 1.35 - 1.28 (m, 1H); LCMS (電灑) m/z 503.1 (M+H)+. | B |
| 76 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.56 (s, 1H), 12.82 (s, 1H), 8.71 (br s, 1H), 8.13 (s, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.84 (s, 1H), 7.54 (d, J=8.4 Hz, 1H), 5.13 - 4.98 (m, 1H), 3.38 (br s, 4H), 2.66 (br s, 4H), 2.19 - 2.10 (m, 1H), 1.79 - 1.73 (m, 1H), 1.35 - 1.28 (m, 1H); LCMS (電灑) m/z 489.1 (M+H)+. | B |
| 77 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.18 (s, 1H), 12.78 (s, 1H), 8.08 (s, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.73 (s, 1H), 7.51 (d, J=8.4 Hz, 1H), 5.12 - 4.96 (m, 1H), 3.65 (br s, 4H), 2.19 - 2.10 (m, 1H), 1.95 (br s, 4H), 1.77 - 1.73 (m, 1H), 1.35 - 1.28 (m, 1H); LCMS (電灑) m/z 473.1 (M+H)+. | B |
| 78 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.17 (s, 1H), 12.79 (s, 1H), 8.09 (s, 1H), 7.85 (d, J=8.4 Hz, 1H), 7.75 (s, 1H), 7.83 (d, J=6.4, Hz, 1H), 5.14 - 4.97 (m, 2H), 4.41 (s, 1H), 3.97 (s, 2H), 3.73 - 3.35 (m, 2H), 2.29 - 2.18 (m, 1H), 2.10 - 1.98 (m, 1H), 1.94 - 1.85 (m, 1H), 1.82 - 1.70 (m, 1H), 1.38 - 1.27 (m, 1H); LCMS (電灑) m/z 490.10 (M+H)+. | B |
| 79 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.75 (s, 1H), 12.84 (s, 1H), 8.20 (s, 1H), 7.94 - 7.82 (m, 2H), 7.60 (d, J=8.4 Hz, 1H), 7.83 (d, J=6.4, Hz, 1H), 5.18 - 4.87 (m, 2H), 3.52 (q, J=5.2Hz, 2H), 3.06 (t, J=5.6Hz, 2H), 2.29 - 2.18 (m, 1H), 1.83 - 1.69 (m, 1H), 1.39 - 1.27 (m, 1H); LCMS (電灑) m/z 481.05 (M+H)+. | B |
| 80 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.78 (br s, 1H), 12.81 (s, 1H), 8.14 (d, J=1.4 Hz, 1H), 7.88 (d, J=8.4 Hz, 1H), 7.86 - 7.79 (m, 1H), 7.55 (dd, J=1.8, 8.4 Hz, 1H), 5.25 - 4.85 (m, 1H), 4.15 (s, 3H), 2.30 - 2.18 (m, 1H), 1.85 - 1.68 (m, 1H), 1.33 (tdd, J=6.4, 9.0, 12.7 Hz, 1H); LCMS (電灑) m/z 435.3 (M+H)+. | B |
| 81 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.77 (s, 1H), 12.82 (s, 1H), 8.16 (d, J = 1.5 Hz, 1H), 7.92 - 7.87 (m, 1H), 7.84 - 7.80 (m, 1H), 7.62 - 7.53 (m, 1H), 5.27 - 4.92 (m, 1H), 4.38 (q, J = 7.0 Hz, 2H), 2.30 - 2.20 (m, 1H), 1.88 - 1.71 (m, 1H), 1.42 (t, J = 7.0 Hz, 3H), 1.38 - 1.29 (m, 1H); LCMS (電灑) m/z 449.1 (M+H)+. | B |
| 82 |  | 1H NMR (400 MHz, DMSO-d 6) δ 7.91 (s, 1H), 7.74 (s, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.40 (dd, J=1.6, 6.8, Hz, 1H), 5.02 - 4.78 (m, 1H), 3.23 (t, J=5.6Hz, 2H), 2.99 (d, J=4Hz, 3H), 2.80 (t, J=6.0 2H), 2.09 - 1.99 (m, 1H), 1.74 - 1.62 (m, 1H), 1.16 - 1.07 (m, 1H); LCMS (電灑) m/z 477.10 (M+H)+. | B |
| 83 |  | 1H NMR (400 MHz, DMSO-d 6) δ 8.07 (d, J= 1.6 Hz, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.78 (s, 1H), 7.51 (dd, J=2.0, 6.4 Hz, 1H), 5.14 - 4.91 (m, 1H), 3.48 (m, 2H), 3.16 (t, J=12 Hz 2H), 2.87 - 2.78(m, 1H), 2.24 - 2.15 (m, 1H), 1.85 (d, J= 10.4 Hz, 2H), 1.80 - 1.68 (m, 1H), 1.66 - 1.54 (m, 2H), 1.33 - 1.24 (m, 1H); LCMS (電灑) m/z 503.10 (M+H)+. | B |
| 84 |  | 1H NMR (400 MHz, DMSO-d 6) δ 8.10 (d, J = 1.6 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.53 (dd, J = 1.6, 8.0 Hz, 1H), 5.15 - 4.93 (m, 1H), 3.26 - 3.17 (m, 2H), 3.12 - 2.96 (m, 2H), 2.89 - 2.81 (m, 1H), 2.26 - 2.17 (m, 1H), 1.91 - 1.68 (m, 4H), 1.35 - 1.23 (m, 2H); LCMS (電灑) m/z 503.1 (M+H)+. | B |
| 85 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.94 (s, 1H), 12.83 (s, 1H), 8.15 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.56 (d, J = 8.0 Hz, 1H), 5.14 - 4.97 (m, 1H), 3.61 (s, 3H), 3.41 - 3.38 (m, 2H), 2.87 - 2.84 (m, 2H), 2.78 (s, 6H), 2.26-2.23 (m, 1H), 1.73 - 1.65 (m, 1H), 1.31 - 1.23 (m, 1H); LCMS (電灑) m/z 505.1 (M+H)+. | B |
| 86 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.94 (s, 1H), 12.85 (s, 1H), 8.19 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.60 (d, J = 8.0 Hz, 1H), 5.14 - 4.97 (m, 1H), 3.61 - 3.57 (m, 2H), 3.04 - 3.01 (m, 2H), 2.87 - 2.84 (m, 2H), 2.26-2.23 (m, 1H), 1.73 - 1.65 (m, 1H), 1.64 - 1.61 (m, 2H), 1.31 - 1.23 (m, 1H); LCMS (電灑) m/z 495.1 (M+H)+. | B |
| 87 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.86 (s, 1H), 12.84 (s, 1H), 8.19 (d, J = 1.6 Hz, 1H), 8.13 - 8.05 (m, 1H), 7.95 - 7.85 (m, 2H), 7.59 (dd, J = 1.6, 8.4 Hz, 1H), 5.18 - 4.95 (m, 1H), 3.66 (s, 2H), 2.58 (d, J = 1.4 Hz, 3H), 2.29 - 2.21 (m, 1H), 1.83 - 1.69 (m, 1H), 1.38 - 1.28 (m, 1H); LCMS (電灑) m/z 509.1 (M+H)+. | B |
| 88 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.56 (s, 1H), 12.83 (s, 1H), 8.19 (d, J = 1.6 Hz, 1H), 7.93 - 7.81 (m, 2H), 7.59 (dd, J = 2.0, 8.0 Hz, 1H), 7.20 (s, 1H), 5.17 - 4.95 (m, 2H), 4.01 (s, J = 8.8 Hz, 1H), 3.91 - 3.82 (m, 1H), 3.67 - 3.60 (m, 1H), 3.55 (t, J = 5.2 Hz, 2H), 2.29 - 2.21 (m, 1H), 1.83 - 1.70 (m, 1H), 1.38 - 1.28 (m, 1H); LCMS (電灑) m/z 519.1 (M+H)+. | B |
| 89 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.25 (s, 1H), 12.78 (s, 1H), 8.09 (d, J = 1.6 Hz, 1H), 7.90 - 7.70 (m, 2H), 7.52 (dd, J = 1.6, 8.4 Hz, 1H), 7.20 (s, 1H), 5.67 - 5.47 (s, 1H), 5.17 - 4.93 (m, 1H), 4.43 - 4.16 (m, 2H), 4.04 - 3.96 (m, 1H), 3.89 - 3.52 (m, 2H), 2.86 (s, 3H), 2.29 - 2.20 (m, 1H), 1.83 - 1.68 (m, 1H), 1.38 - 1.27 (m, 1H); LCMS (電灑) m/z 533.1 (M+H)+ | B |
| 90 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.13 (s, 1H), 12.78 (s, 1H), 8.10 (d, J = 1.6 Hz, 1H), 7.89 - 7.68 (m, 2H), 7.52 (dd, J = 2.4, 8.8 Hz, 1H), 7.21 (s, 1H), 5.82 - 5.62 (s, 1H), 5.17 - 4.94 (m, 1H), 4.33 - 4.23 (m, 1H), 4.15 - 4.06 (m, 1H), 3.67 - 3.43 (m, 2H), 3.34 - 3.26 (m, 1H), 3.12 - 3.05 (m, 1H), 2.31 - 2.15 (m, 2H), 1.84 - 1.69 (m, 1H), 1.39 - 1.26 (m, 1H); LCMS (電灑) m/z 533.1 (M+H)+. | B |
| 91 |  | 1H NMR (400 MHz, DMSO-d 6) δ 7.85 (s, 1H), 7.76 (s, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.36 (dd, J = 1.6, 8.4 Hz, 1H), 5.02 - 4.78 (m, 1H), 4.04 - 3.87 (m, 1H), 3.78 - 3.61 (m, 2H), 3.58 - 3.48 (m, 1H), 2.72 - 2.59 (m, 2H), 2.34 - 2.26 (m, 1H), 2.09 - 1.92 (m, 2H), 1.74 - 1.61 (m, 4H), 1.15 - 1.02 (m, 1H); LCMS (電灑) m/z 503.1 (M+H)+. | B |
| 92 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (s, 1H), 12.82 (s, 1H), 8.22 (s, 1H), 8.14 (s, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.85 (s, 1H), 7.55 (d, J = 8.0 Hz, 1H), 5.14 - 4.97 (m, 1H), 2.89 (m, 2H), 2.65 (t, J = 5.2 Hz, 2H), 2.26-2.23 (m, 1H), 1.73 - 1.65 (m, 1H), 1.31 - 1.23 (m, 1H); LCMS (電灑) m/z 491.1 (M+H)+. | B |
| 93 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (s, 1H), 12.81 (s, 1H), 8.22 (s, 1H), 8.14 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 5.14 - 4.96 (m, 1H), 3.64-3.61 (m, 2H), 3.35-3.32 (m, 2H), 3.02 (s, 3H), 2.26-2.23 (m, 1H), 1.73 - 1.65 (m, 1H), 1.31 - 1.23 (m, 1H); LCMS (電灑) m/z 478.1 (M+H)+. | B |
| 94 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.51 (s, 1H), 12.82 (s, 1H), 8.49 (br, 1H), 8.38 (br, 1H), 8.14 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.72 (s, 1H), 7.55 (d, J = 8.8 Hz, 1H), 5.16 - 4.97 (m, 1H), 3.96-3.91 (m, 2H), 3.67-3.64 (m, 2H), 2.90 (s, 3H), 2.26-2.23 (m, 1H), 1.79 - 1.72 (m, 1H), 1.37 - 1.30 (m, 1H), 1.08 (t, J = 7.2 Hz, 1H); LCMS (電灑) m/z 503.1 (M+H)+. | B |
| 95 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.18 (s, 1H), 12.78 (s, 1H), 8.57 (br, 2H), 8.08 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.51 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 5.16 - 4.95 (m, 1H), 4.00 (m, 2H), 3.92 (m, 2H), 3.71 (br, 2H), 3.05 (br, 1H), 2.25 - 2.20 (m, 1H), 1.78 - 1.68 (m, 1H), 1.36 - 1.28 (m, 1H), 1.08 (t, J = 7.2 Hz, 1H); LCMS (電灑) m/z 489.1 (M+H)+. | B |
| 96 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.26 (br s, 1H), 12.74 (s, 1H), 8.00 (d, J = 1.4 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.60 (s, 1H), 7.44 (dd, J = 1.7, 8.3 Hz, 1H), 6.81 (s, 1H), 5.16 - 4.94 (m, 1H), 3.98 (s, 3H), 2.31 (s, 3H), 2.27 - 2.19 (m, 1H), 1.82 - 1.68 (m, 1H), 1.32 (tdd, J = 6.3, 9.0, 12.8 Hz, 1H); LCMS(電灑) m/z 397.4 (M+H+). | B |
| 97 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (br s, 1H), 12.76 (s, 1H), 8.04 (d, J=1.3 Hz, 1H), 7.86 (d, J=8.3 Hz, 1H), 7.69 (s, 1H), 7.46 (dd, J=1.7, 8.3 Hz, 1H), 5.18 - 4.89 (m, 1H), 4.08 (d, J=0.9 Hz, 3H), 2.29 - 2.22 (m, 1H), 2.20 (d, J=3.2 Hz, 3H), 1.83 - 1.69 (m, 1H), 1.32 (tdd, J=6.4, 8.8, 12.8 Hz, 1H); LCMS(電灑) m/z 415.4 (M +H+). | B |
| 98 |  | 1H NMR (400 MHz, DMSO-d 6) 13.42 (br s, 1H), 12.78 (s, 1H), 8.05 (d, J=1.3 Hz, 1H), 7.86 (d, J=8.3 Hz, 1H), 7.68 (s, 1H), 7.47 (dd, J=1.5, 8.3 Hz, 1H), 5.22 - 4.90 (m, 1H), 4.30 (br d, J=7.1 Hz, 2H), 2.23 (br d, J=7.0 Hz, 1H), 2.19 (d, J=3.1 Hz, 3H), 1.80 - 1.70 (m, 1H), 1.39 (t, J=7.0 Hz, 3H), 1.35 - 1.28 (m, 1H); LCMS(電灑) m/z 429.4 (M +H+). | B |
| 99 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.76 (s, 1H), 12.84 (s, 1H), 8.19 (d, J=2.0 Hz, 1H), 7.94 - 7.84 (m, 2H), 7.59 (dd, J=1.6, 8.0 Hz, 1H), 5.17 - 4.95 (m, 1H), 4.03 (s, 2H), 3.01 (s, 3H), 2.81 (s, 3H), 2.29 - 2.20 (m, 1H), 1.82 - 1.70 (m, 1H), 1.38 - 1.28 (m, 1H); LCMS (電灑) m/z 522.10 (M+H)+. | B |
| 100 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (s, 1H), 12.80 (s, 1H), 8.12 (s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.54 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 5.14 - 4.96 (m, 1H), 3.62 (s, 2H), 3.37 (s, 6H), 3.15 (s, 3H), 2.25 - 2.20 (m, 1H), 1.78 - 1.68 (m, 1H), 1.34 - 1.28 (m, 1H); LCMS (電灑) m/z 519.1 (M+H)+. | B |
| 101 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.22 (br s, 1H), 12.74 (s, 1H), 8.00 (d, J = 1.3 Hz, 1H), 7.83 (d, J = 8.3 Hz, 1H), 7.60 (s, 1H), 7.44 (dd, J = 1.8, 8.3 Hz, 1H), 6.79 (s, 1H), 5.17 - 4.93 (m, 1H), 4.27 (q, J = 7.1 Hz, 2H), 2.29 (s, 3H), 2.27 - 2.20 (m, 1H), 1.82 - 1.69 (m, 1H), 1.46 (t, J = 7.0 Hz, 3H), 1.32 (tdd, J = 6.4, 8.9, 12.8 Hz, 1H); LCMS(電灑) m/z 410.9 (M+H+). | B |
| 102 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.16 (br s, 1H), 12.77 (s, 1H), 8.00 (d, J=1.6 Hz, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.55 (s, 1H), 7.42 (dd, J=1.6, 8.3 Hz, 1H), 5.18 - 4.93 (m, 1H), 2.96 (s, 3H), 2.96 (s, 3H), 2.56 - 2.52 (m, 2H), 2.29 - 2.20 (m, 1H), 1.82 - 1.71 (m, 1H), 1.32 (tdd, J=6.6, 9.0, 12.8 Hz, 1H), 1.07 (t, J=7.4 Hz, 3H); LCMS(電灑) m/z 442.2 (M +H+). | B |
| 103 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (br s, 1H), 12.80 (s, 1H), 8.05 (d, J = 1.3 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.64 (s, 1H), 7.45 (dd, J = 1.8, 8.3 Hz, 1H), 5.18 - 4.92 (m, 1H), 2.59 (br d, J = 6.9 Hz, 2H), 2.52 (br s, 3H), 2.29 - 2.20 (m, 1H), 1.82 - 1.70 (m, 1H), 1.37 - 1.28 (m, 1H), 1.08 (t, J = 7.3 Hz, 3H); LCMS(電灑) m/z 445.3 (M+H+). | B |
| 104 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (br s, 1H), 12.77 (br s, 1H), 8.03 (s, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.64 (s, 1H), 7.46 (br d, J=8.3 Hz, 1H), 5.18 - 4.89 (m, 1H), 2.95 (s, 6H), 2.28 - 2.22 (m, 1H), 2.16 (br d, J=3.2 Hz, 3H), 1.83 - 1.69 (m, 1H), 1.38 - 1.24 (m, 1H); LCMS(電灑) m/z 428.2 (M+H+). | B |
| 105 |  | 1H NMR (400MHz, CHLOROFORM-d) δ 12.79 (br s, 1H), 8.09 (d, J = 1.6 Hz, 1H), 7.86 (d, J = 8.3 Hz, 1H), 7.71 (s, 1H), 7.51 (dd, J = 1.8, 8.3 Hz, 1H), 7.48 (d, J = 9.3 Hz, 1H), 5.21 - 4.92 (m, 1H), 2.28 - 2.22 (m, 1H), 2.21 (s, 3H), 1.83 - 1.69 (m, 1H), 1.32 (ddd, J = 2.6, 6.4, 12.8 Hz, 1H); LCMS(電灑) m/z 417.1 (M +H+). | B |
| 106 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.84 (br s, 1H), 12.79 (s, 1H), 8.03 (d, J=1.6 Hz, 1H), 7.88 (d, J=8.3 Hz, 1H), 7.70 (br s, 1H), 7.43 (dd, J=1.8, 8.3 Hz, 1H), 5.23 - 4.89 (m, 1H), 2.61 (br d, J=6.0 Hz, 2H), 2.29 - 2.20 (m, 1H), 1.82 - 1.69 (m, 1H), 1.37 - 1.27 (m, 1H), 1.09 (t, J=7.4 Hz, 3H); LCMS(電灑) m/z 417.1 (M +H+). | B |
| 107 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.43 (s, 1H), 12.78 (s, 1H), 8.02 (s, 1H), 7.87 (d, J=8.4 Hz, 1H), 7.59 (s, 1H), 7.45 - 7.42 (m, 1H), 5.15 - 4.97 (m, 1H), 4.34 - 4.28 (m, 2H), 2.59 - 2.53 (m, 2H), 2.27 - 2.23 (m, 1H), 1.85 - 1.75 (m, 1H), 1.40 (t, J = 6.8 Hz, 3H), 1.36 - 1.32 (m, 1H), 1.09 (t, J = 7.2 Hz, 3H); LCMS(電灑) m/z 443.2 (M +H+). | B |
| 108 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.27 (s, 1H), 12.82 (s, 1H), 10.11 (s, 1H), 8.20 (d, J = 1.6 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 1.1 Hz, 1H), 7.60 (dd, J = 1.7, 8.3 Hz, 1H), 5.18 - 4.96 (m, 1H), 2.26 (ddd, J = 2.2, 4.5, 6.5 Hz, 1H), 2.19 (s, 3H), 1.77 (tdd, J = 3.2, 6.8, 19.9 Hz, 1H), 1.33 (tdd, J = 6.3, 9.0, 12.8 Hz, 1H); LCMS(電灑) m/z 462.1 (M +H+). | B |
| 109 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.35 - 13.37 (m, 1H), 12.79 (s, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.88 (d, J=8.3 Hz, 1H), 7.79 (br s, 1H), 7.48 (dd, J=1.8, 8.3 Hz, 1H), 5.22 - 4.90 (m, 1H), 2.27 - 2.19 (m, 4H), 1.83 - 1.69 (m, 1H), 1.32 (tdd, J=6.4, 9.0, 12.9 Hz, 1H); LCMS(電灑) m/z 403.2 (M +H+). | B |
| 110 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36 (br s, 1H), 12.77 (s, 1H), 8.04 (d, J = 1.5 Hz, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.67 (s, 1H), 7.48 (dd, J = 1.7, 8.3 Hz, 1H), 5.16 - 4.94 (m, 1H), 2.97 (d, J = 2.1 Hz, 6H), 2.27 - 2.22 (m, 1H), 2.20 (s, 3H), 1.83 - 1.69 (m, 1H), 1.39 - 1.26 (m, 1H); LCMS(電灑) m/z 460 (M+H+). | B |
| 111 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.77 - 13.52 (m, 1H), 12.80 (s, 1H), 8.09 (d, J = 1.5 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.52 (dd, J = 1.8, 8.3 Hz, 1H), 5.20 - 4.93 (m, 1H), 2.55 (s, 3H), 2.30 - 2.24 (m, 1H), 2.22 (s, 3H), 1.83 - 1.70 (m, 1H), 1.32 (tdd, J = 6.4, 8.9, 12.8 Hz, 1H); LCMS(電灑) m/z 462.05 (M +H+). | B |
| 112 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.16 (s, 1H), 12.83 (s, 1H), 8.14 (d, J = 1.5 Hz, 1H), 7.92 (d, J = 8.3 Hz, 1H), 7.85 (d, J = 1.2 Hz, 1H), 7.53 (dd, J = 1.7, 8.3 Hz, 1H), 5.19 - 4.94 (m, 1H), 3.50 (s, 3H), 2.29 (br s, 1H), 2.24 (d, J = 2.9 Hz, 3H), 1.85 - 1.69 (m, 1H), 1.41 - 1.24 (m, 1H); LCMS(電灑) m/z 463.1 (M +H+). | B |
| 113 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.94 - 12.86 (m, 1H), 12.83 - 12.74 (m, 1H), 9.90 (br s, 1H), 8.09 (br s, 1H), 7.88 (br d, J = 7.9 Hz, 1H), 7.66 (br s, 1H), 7.49 (br d, J = 7.4 Hz, 1H), 5.19 - 4.95 (m, 1H), 2.28 - 2.23 (m, 1H), 2.20 (br s, 3H), 2.16 (br s, 3H), 1.84 - 1.69 (m, 1H), 1.42 - 1.25 (m, 1H); LCMS(電灑) m/z 442.0 (M +H+). | B |
| 114 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.05 (s, 1H), 10.78 (s, 1H), 8.08 (s, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.72 (s, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.45 (d, J = 12.4 Hz, 1H), 5.14 - 4.95 (m, 1H), 3.37 (s, 3H), 2.25 - 2.20 (m, 1H), 1.78 - 1.68 (m, 1H), 1.34 - 1.28 (m, 10H); LCMS (電灑) m/z 549.1 (M+H)+. | B |
| 115 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.88 (s, 1H), 12.79 (s, 1H), 8.25 (s, 1H), 8.11 (s, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.76 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 6.45 (d, J = 12.4 Hz, 1H), 5.13 - 4.96 (m, 1H), 4.04 - 3.99 (m, 1H), 3.23 (s, 3H), 2.25 - 2.20 (m, 1H), 1.78 - 1.68 (m, 1H), 1.34 - 1.28 (m, 1H); LCMS (電灑) m/z 449.1 (M+H)+. | B |
| 116 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.28 (s, 1H), 12.87 - 12.78 (m, 1H), 8.14 (d, J = 1.5 Hz, 1H), 7.91 (d, J = 8.3 Hz, 1H),7.80 (d, J = 1.3 Hz, 1H), 7.53 (dd, J = 1.8, 8.4 Hz, 1H), 5.18 - 4.95 (m, 1H), 3.98 (s, 3H), 2.21 (d, J = 3.1 Hz, 3H), 1.91 - 1.88 (m,1H), 1.69 (br d, J = 2.8 Hz, 1H), 1.34 - 1.29 (m, 1H); LCMS(電灑) m/z 443.1(M+H+). | B |
| 117 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.07 (br s, 1H), 12.81 (s, 1H), 8.08 (d, J=1.5 Hz, 1H), 7.86 (d, J=8.4 Hz, 2H), 7.50 (dd, J=1.8, 8.3 Hz, 1H), 5.19 - 4.94 (m, 1H), 2.29 - 2.20 (m, 4H), 1.84 - 1.68 (m, 1H), 1.38 - 1.26 (m, 1H); LCMS(電灑) m/z 435.1 (M +H+). | B |
| 118 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.87 - 13.43 (m, 1H), 12.78 (s, 1H), 8.07 (s, 1H), 7.85 (d, J = 8.4 Hz, 1H), 7.73 (s, 1H), 7.50 (dd, J = 1.3, 8.4 Hz, 1H), 5.21 - 4.93 (m, 1H), 4.35 (q, J = 7.0 Hz, 2H), 2.30 - 2.19 (m, 4H), 1.84 - 1.70 (m, 1H), 1.41 (t, J = 7.0 Hz, 3H), 1.37 - 1.27 (m, 1H); LCMS(電灑) m/z 461.2 (M+H+). | B |
| 119 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (br s, 1H), 12.87 (s, 1H), 8.24 (d, J = 1.6 Hz, 1H), 8.00 (s, 1H), 7.94 (d, J = 8.4 Hz, 1H), 7.62 (dd, J = 1.8, 8.4 Hz, 1H), 5.17 - 4.95 (m, 1H), 3.56 (s, 3H), 2.29 - 2.22 (m, 1H), 1.83 - 1.71 (m, 1H), 1.37 - 1.29 (m, 1H); LCMS(電灑) m/z 483 (M+H+). | B |
| 120 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.22 - 11.13 (m, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.95 - 7.87 (m, 1H), 7.72 - 7.70 (m, 1H), 6.96 - 6.93 (m, 1H), 6.92 - 6.89 (m, 1H), 5.07 - 4.81 (m, 1H), 3.21 (s, 3H), 2.30 - 2.25 (m, 3H), 2.25 - 2.23 (m, 1H), 2.20 - 2.09 (m, 1H), 1.79 (s, 3H), 1.74 - 1.63 (m, 1H), 1.28 - 1.09 (m, 1H); LCMS(電灑) m/z 456.1 (M +H+). | B |
| 121 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.45 (br s, 1H), 12.85 (s, 1H), 8.23 (d, J = 1.6 Hz, 1H), 7.94 - 7.88 (m, 2H), 7.62 (dd, J = 1.8, 8.4 Hz, 1H), 5.21 - 4.90 (m, 1H), 2.29 - 2.17 (m, 1H), 1.85 - 1.62 (m, 1H), 1.42 - 1.26 (m, 1H); LCMS(電灑) m/z 449.2 (M +H+). | B |
| 122 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.57 (s, 1H), 12.86 (s, 1H), 8.36 - 8.16 (m, 1H), 7.96 - 7.91 (m, 2H), 7.63 (dd, J = 1.8, 8.4 Hz, 1H), 5.22 - 4.90 (m, 1H), 4.00 (s, 3H), 2.30 - 2.20 (m, 1H), 1.83 - 1.68 (m, 1H), 1.45 - 1.21 (m, 1H); LCMS(電灑) m/z 463.1 (M +H+). | B |
| 123 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.06 - 13.79 (m, 1H), 12.83 (s, 1H), 8.21 (d, J = 1.6 Hz, 1H), 7.91 - 7.89 (m, 1H), 7.63 (d, J = 1.7 Hz, 1H), 7.62 - 7.59 (m, 1H), 5.15 - 4.96 (m, 1H), 3.23 (s, 3H), 2.27 - 2.23 (m, 1H), 1.82 (s, 3H), 1.76 - 1.69 (m, 1H), 1.36 - 1.30 (m, 1H); LCMS(電灑) m/z 476.1 (M +H+). | B |
| 124 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.94 (br s, 1H), 8.10 (d, J = 1.5 Hz, 1H), 7.91(d, J = 8.3 Hz, 1H), 7.68 (s, 1H), 7.51 (dd, J = 1.7, 8.3 Hz, 1H), 5.19 - 4.92 (m, 1H), 2.31 - 2.25 (m, 1H), 2.19 (d, J = 3.1 Hz,3H), 1.82 - 1.71 (m, 1H), 1.37 - 1.28 (m, 1H); LCMS(電灑) m/z 429.1(M+H+). | B |
| 125 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.86 - 13.55 (m, 1H), 8.21 (d, J = 1.5 Hz, 1H), 7.92 (s, 1H), 7.90 (s, 1H), 7.61 (dd, J = 1.8, 8.4 Hz, 1H), 5.17 - 4.94 (m, 1H), 3.13 (s, 3H), 2.94 (s, 3H), 2.28 - 2.22 (m, 1H), 1.81 - 1.72 (m, 1H), 1.36 - 1.28 (m, 1H); LCMS(電灑) m/z 475.9 (M +H+). | B |
| 126 |  | 1H NMR (400 MHz, DMSO-d 6) δ 8.16 (d, J=1.6 Hz, 1H), 7.95 (d, J=3.2 Hz, 1H), 7.89 (d, J=8.3 Hz, 1H), 7.56 (dd, J=1.8, 8.3 Hz, 1H), 5.18 - 4.93 (m, 1H), 2.29 - 2.20 (m, 1H), 1.83 - 1.70 (m, 1H), 1.32 (tdd, J=6.4, 9.0, 12.8 Hz, 1H); LCMS(電灑) m/z 423.1 (M +H+). | B |
| 127 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.71 - 13.47 (s, 1H), 12.98 - 12.70 (s, 1H), 8.65 - 8.55 (s, 1H), 8.21 (s, 1H), 7.97 - 7.88 (m, 1H), 7.85 (s, 1H), 7.63 - 7.56 (m, 1H), 5.20 - 4.91 (m, 1H), 2.91 (br d, J = 4.3 Hz, 3H), 2.30 - 2.21 (m, 1H), 1.84 - 1.69 (m, 1H), 1.41 - 1.28 (m, 1H); LCMS(電灑) m/z 462.0 (M +H+). | B |
| 128 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.69 (s, 1H), 12.86 (s, 1H), 8.24 (d, J = 1.5 Hz, 1H), 7.97 - 7.87 (m, 2H), 7.63 (dd, J = 1.7, 8.4 Hz, 1H), 5.22 - 4.92 (m, 1H), 2.77 (d, J = 6.2 Hz, 3H), 2.31 - 2.21 (m, 1H), 1.83 - 1.70 (m, 1H), 1.25-1.32 (m, J = 2.5, 6.3, 12.8 Hz, 1H); LCMS(電灑) m/z 447.2 (M+H+). | B |
| 129 |  | 1H NMR (400 MHz, DMSO-d 6) δ 8.14 (s, 1H), 7.92 - 7.82 (m, 2H), 7.59 - 7.51 (m, 1H), 5.18 - 4.92 (m, 1H), 4.51 - 4.40 (m, 1H), 4.11 - 3.85 (m, 3H), 2.94 (s, 3H), 2.89 - 2.16 (m, 1H), 2.03 - 1.88 (m, 1H), 1.83 - 1.68 (m, 1H), 1.38 - 1.27 (m, 1H); LCMS (電灑) m/z 489.10 (M+H)+. | B |
| 130 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.86 - 13.56 (m, 1H), 12.93 - 12.67 (m, 1H), 8.01 (s, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.63 (s, 1H), 7.40 (br d, J = 8.5 Hz, 1H), 5.20 - 4.90 (m, 1H), 3.01 (s, 6H), 2.28 - 2.18 (m, 1H), 1.82 - 1.69 (m, 1H), 1.31 (ddd, J = 2.4, 6.4, 12.5 Hz, 1H); LCMS(電灑) m/z 482.1 (M+H+). | B |
| 131 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.39 (s, 1H), 12.82 (br d, J = 1.7 Hz, 1H), 8.13 (s, 1H), 7.91 (d, J = 8.3 Hz, 1H), 7.76 (s, 1H), 7.52 (dd, J = 1.4, 8.3 Hz, 1H), 5.18 - 4.92 (m, 1H), 2.74 (d, J = 6.2 Hz, 3H), 2.24 (br d, J = 3.2 Hz, 3H), 1.86 - 1.66 (m, 1H), 1.32 (tdd, J = 6.5, 8.8, 12.7 Hz, 1H); LCMS(電灑) m/z 427.10 (M +H+). | B |
| 132 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.19 (s, 1H), 12.81 (br s, 1H), 8.11 (d, J = 1.5 Hz, 1H), 7.90 (d, J = 8.3 Hz, 1H), 7.70 (d, J = 1.1 Hz, 1H), 7.50 (dd, J = 1.7, 8.3 Hz, 1H), 5.18 - 4.93 (m, 1H), 2.90 (d, J = 4.5 Hz, 3H), 2.29 - 2.24 (m, 1H), 2.22 (d, J = 3.1 Hz, 3H), 1.87 - 1.67 (m, 1H), 1.33 (tdd, J = 6.4, 8.9, 12.7 Hz, 1H); LCMS(電灑) m/z 442.1 (M +H+). | B |
| 133 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.45 (br s, 1H), 12.81 (s, 1H), 8.15 (d, J = 1.5 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.57 (dd, J = 1.8, 8.4 Hz, 1H), 5.17 - 4.92 (m, 1H), 3.26 (q, J = 6.4 Hz, 2H), 2.98 (s, 3H), 2.30 - 2.21 (m, 1H), 1.85 - 1.70 (m, 1H), 1.33 (tdd, J = 6.5, 8.8, 12.8 Hz, 1H), 1.09 (t, J = 7.1 Hz, 3H); LCMS(電灑) m/z 462.1(M+H+). | B |
| 134 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38 (br s, 1H), 8.10 (d, J = 1.3 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.74 (s, 1H), 7.51 (dd, J = 1.8, 8.4 Hz, 1H), 5.18 - 4.91 (m, 1H), 3.12 (s, 3H), 2.93 (s, 3H), 2.24 (br d, J = 2.1 Hz, 1H), 2.21 (d, J = 2.8 Hz, 3H), 1.83 - 1.67 (m, 1H), 1.31 (ddd, J = 2.8, 6.3, 12.7 Hz, 1H); LCMS(電灑) m/z 455.9 (M+H+). | B |
| 135 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.50 (s, 1H), 12.85 (s, 1H), 8.21 (d, J = 1.4 Hz, 1H), 8.04 ( s, 2H), 7.92 (d, J = 8.4 Hz,1H), 7.84 (s, 1H), 7.60 (dd, J = 1.7, 8.3 Hz, 1H), 5.20 - 4.94 (m, 1H), 2.32 - 2.18 (m, 1H), 1.84 - 1.69 (m, 1H), 1.29~ 1.36(m, 1H); LCMS(電灑) m/z 448.1 (M+H+). | B |
| 136 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.12 (br s, 1H), 12.76 (br d, J=12.7 Hz, 1H), 8.00 (s, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.54 (s, 1H), 7.43 (dd, J=1.6, 8.2 Hz, 1H), 5.21 - 4.89 (m, 1H), 3.21 (q, J=6.9 Hz, 2H), 2.94 (s, 3H), 2.55 (br d, J=7.6 Hz, 2H), 2.28 - 2.19 (m, 1H), 1.83 - 1.68 (m, 1H), 1.37 - 1.26 (m, 1H), 1.07 (dt, J=4.0, 7.1 Hz, 6H); LCMS(電灑) m/z 456.2 (M+H+). | B |
| 137 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.11 (s, 1H), 8.04 (d, J = 1.4 Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.64 (s, 1H), 7.47 (dd, J = 1.8, 8.3 Hz, 1H), 5.19 - 4.89 (m, 1H), 3.23 - 3.17 (m, 2H), 2.93 (d, J = 1.9 Hz, 3H), 2.28 - 2.20 (m, 1H), 2.17 (d, J = 3.1 Hz, 3H), 1.85 - 1.68 (m, 1H), 1.38 - 1.23 (m, 1H), 1.06 (t, J = 7.1 Hz, 3H); LCMS(電灑) m/z 441.14 (M +H+). | B |
| 138 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.34 (br s, 1H), 8.04 (d, J = 1.3 Hz, 1H), 7.83 (d, J = 8.2 Hz, 1H), 7.68 (s, 1H), 7.49 (dd, J = 1.7, 8.3 Hz, 1H), 5.16 - 4.94 (m, 1H), 3.23 (q, J = 7.1 Hz, 2H), 2.95 (d, J = 2.0 Hz, 3H), 2.28 - 2.22 (m, 1H), 2.20 (s, 3H), 1.82 - 1.68 (m, 1H), 1.31 (tdd, J = 6.2, 8.9, 12.6 Hz, 1H), 1.07 (t, J = 7.1 Hz, 3H); LCMS(電灑) m/z 474.1 (M+H+). | B |
| 139 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.31 (s, 1H), 12.77 (s, 1H), 8.33 (s, 1H), 8.24 (br s, 1H), 7.89 - 7.81 (m, 1H), 7.80 - 7.74 (m, 1H), 7.13 (br d, J = 13.7 Hz, 1H), 5.17 - 4.92 (m, 1H), 2.95 (br s, 6H), 2.27 - 2.18 (m, 1H), 1.82 - 1.69 (m, 1H), 1.31 (br s, 1H); LCMS(電灑) m/z 414.2 (M+H+). | B |
| 140 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.04 (br s, 1H), 12.83 (br s, 1H), 8.47 - 8.36 (m, 2H), 7.92 - 7.83 (m, 2H), 7.45 (br d, J = 11.7 Hz, 1H), 5.19 - 4.95 (m, 1H), 2.30 - 2.20 (m, 1H), 1.84 - 1.70 (m, 1H), 1.34 (ddd, J = 2.4, 6.2, 12.9 Hz, 1H); LCMS(電灑) m/z 455.2 (M+H+). | B |
| 141 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.56 (s, 1 H) 12.81 (s, 1 H) 8.42 (s, 1 H) 8.34 (s, 1 H) 7.89 - 7.82 (m, 2 H) 7.29 (d, J=10.4 Hz, 1 H) 5.14 - 4.97 (m, 1 H) 2.49 (s, 3 H) 2.28 - 2.23 (m, 1 H) 1.80 - 1.73 (m, 1 H) 1.35 - 1.30 (m, 1 H); LCMS(電灑) m/z 416.9 (M+H+). | B |
| 142 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.21 - 13.61 (m, 1 H) 12.76 (s, 1 H) 8.35 (d, J=1.50 Hz, 1 H) 8.31 (s, 1 H) 7.85 - 7.89 (m, 1 H) 7.79 (dd, J=8.38, 1.75 Hz, 1 H) 7.34 - 7.39 (m, 1 H) 7.27 - 7.32 (m, 1 H) 4.93 - 5.17 (m, 1 H) 3.17 (s, 1 H) 2.62 (s, 3 H) 2.20 - 2.29 (m, 1 H) 1.70 - 1.82 (m, 1 H) 1.32 (ddt, J=12.77, 8.93, 6.35, 6.35 Hz, 1 H); LCMS(電灑) m/z 399.0 (M+H+). | B |
| 143 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.77 (br s, 1H), 8.15 - 7.99 (m, 2H), 7.83 (br d, J = 8.3 Hz, 1H), 7.45 (br d, J = 8.1 Hz, 1H), 7.18 (br s, 1H), 5.17 - 4.93 (m, 1H), 2.33 (s, 3H), 2.25 (br s, 1H), 1.84 - 1.70 (m, 1H), 1.37 - 1.27 (m, 1H); LCMS(電灑) m/z 346.1(M+H+). | B |
| 144 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (br s, 1H), 12.82 (br s, 1H), 8.11 (s, 1H), 7.98 (s, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.55 (td, J=2.1, 8.3 Hz, 1H), 7.47 (dd, J=0.7, 9.7 Hz, 1H), 5.18 - 4.90 (m, 1H), 2.79 (s, 3H), 2.63 (d, J=1.0 Hz, 3H), 2.24 (td, J=6.9, 13.6 Hz, 1H), 1.85 - 1.67 (m, 1H), 1.39 - 1.25 (m, 1H); LCMS(電灑) m/z 442.2 (M+H+). | B |
| 145 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (br s, 1H), 12.82 (br s, 1H), 8.11 (s, 1H), 7.98 (s, 1H), 7.85 (d, J=8.3 Hz, 1H), 7.55 (td, J=2.1, 8.3 Hz, 1H), 7.47 (dd, J=0.7, 9.7 Hz, 1H), 5.18 - 4.90 (m, 1H), 2.79 (s, 3H), 2.63 (d, J=1.0 Hz, 3H), 2.24 (td, J=6.9, 13.6 Hz, 1H), 1.85 - 1.67 (m, 1H), 1.39 - 1.25 (m, 1H); LCMS(電灑) m/z 442.2 (M+H+). | B |
| 146 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.04 (s, 1H), 12.86 (s, 1H), 8.19 (d, J=8.8 Hz, 1H), 7.74 (s, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.48 (d, J=8.4 Hz, 1H), 7.29 (d, J=8.4 Hz, 1H), 5.14-4.93 (m, 1H), 2.35 (s, 3H), 2.29-2.20 (m, 1H), 1.77-1.70 (m, 1H), 1.35-1.26 (m, 1H); LCMS (電灑) m/z 368.1 (M+H)+. | D |
| 147 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.96 (s, 1H), 8.25 (d, J=8.0 Hz, 1H), 7.80 (s, 1H), 7.71 (d, J=8.4 Hz, 1H), 7.42 (d, J=10.0 Hz, 1H), 5.17-4.98 (m, 1H), 2.69 (s, 3H), 2.28-2.21 (m, 1H), 1.81-1.71 (m, 1H), 1.37-1.28 (m, 1H); LCMS (電灑) m/z 386.1 (M+H)+. | D |
| 148 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.10 (br s, 1H), 12.95 (s, 1H), 8.21 (d, J=8.0 Hz, 1H), 7.53 (d, J=8.0 Hz, 1H), 7.37 (d, J=10.1 Hz, 1H), 5.18 - 4.97 (m, 1H), 2.27 (s, 3H), 2.16 (td, J=6.9, 13.8 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS (電灑) m/z 432.1 (M+H)+. | D |
| 149 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.77 (s, 1H), 12.97 (s, 1H), 8.27 (d, J=8.4 Hz, 1H), 7.93 (s, 1H), 7.82 (d, J=8.5 Hz, 1H), 5.20 - 4.95 (m, 1H), 4.40 (q, J=7.0 Hz, 2H), 2.31 - 2.23 (m, 1H), 1.85 - 1.71 (m, 1H), 1.41 (t, J=6.9 Hz, 3H), 1.38 - 1.30 (m, 1H); LCMS (電灑) m/z 450.2 (M+H)+. | C |
| 150 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.93 (s, 1 H), 8.25 (d, J=8.31 Hz, 1 H), 7.64 - 7.59 (m, 2 H), 7.39 (d, J=11.62 Hz, 1 H), 5.19 - 4.96 (m, 1 H), 3.08 (dt, J=14.15, 7.17 Hz, 1 H), 2.30 - 2.23 (m, 1 H), 1.83 - 1.71 (m, 1 H), 1.40 - 1.32 (m, 1 H),1.31 - 1.23 (m, 6 H); LCMS (電灑) m/z 414.2 (M+H)+. | D |
| 151 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.91 (s, 1 H), 8.25 (d, J=8.56 Hz, 1 H), 8.00 (s, 1 H), 7.95 (d, J=8.44 Hz, 1 H),7.40 (d, J=10.88 Hz, 1 H), z, 1 H), 5.21 - 4.94 (m, 1 H), 2.30 - 2.23 (m, 1 H), 1.84 - 1.69 (m, 1 H), 1.41 - 1.28 (m, 1 H); LCMS (電灑) m/z 387.2 (M+H)+. | D |
| 152 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.18 (br s, 1H), 12.94 (br s, 1H), 8.26 (d, J=8.2 Hz, 1H), 7.72 (s, 1H), 7.68 (d, J=8.3 Hz, 1H), 7.42 (d, J=10.1 Hz, 1H), 5.20 - 4.95 (m, 1H), 2.65 (dq, J=2.4, 7.2 Hz, 2H), 2.27 (m, 1H), 1.85 - 1.69 (m, 1H), 1.34 (m, 1H), 1.11 (t, J=7.0 Hz, 3H); LCMS (電灑) m/z 400.4 (M+H)+. | D |
| 153 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.99 (s, 1H), 8.29 (d, J=8.4 Hz, 1H), 7.91 (d, J=0.9 Hz, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.71 (dd, J=0.9, 9.2 Hz, 1H), 5.20 - 4.96 (m, 1H), 2.31 - 2.23 (m, 1H), 1.84 - 1.71 (m, 1H), 1.40 - 1.31 (m, 1H); LCMS (電灑) m/z 406.3 (M+H)+. | D |
| 154 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (br s, 1H), 12.96 (s, 1H), 8.26 (d, J=8.3 Hz, 1H), 7.89 (s, 1H), 7.83 (d, J=8.3 Hz, 1H), 5.21 - 4.95 (m, 1H), 3.30 (q, J=6.4 Hz, 4H), 2.31 - 2.22 (m, 1H), 1.84 - 1.71 (m, 1H), 1.41 - 1.27 (m, 2H), 1.02 (t, J=7.1 Hz, 6H); LCMS (電灑) m/z 477.3 (M+H)+. | D |
| 155 |  | 1H NMR (400 MHz, DMSO-d 6)) δ 12.93 (s, 1H), 8.25 (d, J=8.6 Hz, 1H), 8.16 (s, 1H), 7.98 (d, J=8.4 Hz, 1H), 7.55 (d, J=10.6 Hz, 1H), 5.22 - 4.93 (m, 1H), 3.73 (s, 3H), 2.31 - 2.22 (m, 1H), 1.85 - 1.70 (m, 1H), 1.41 - 1.28 (m, 1H); LCMS (電灑) m/z 402.4 (M +H+). | D |
| 156 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.94 (s, 1H), 8.29 - 8.21 (m, 1H), 7.80 (d, J=0.8 Hz, 1H), 7.74 (d, J=8.4 Hz, 1H), 7.55 (dd, J=0.8, 9.5 Hz, 1H), 5.20 - 4.95 (m, 1H), 2.32 - 2.27 (m, 1H), 2.26 (s, 3H), 1.84 - 1.71 (m, 1H), 1.35 (tdd, J=6.4, 8.9, 13.0 Hz, 1H); LCMS(電灑) m/z 418.3 (M+H+). | D |
| 157 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.84 (br s, 1H), 13.07 (s, 1H), 8.39 - 8.30 (m, 2H), 8.08 (d, J=8.4 Hz, 1H), 7.77 (d, J=9.5 Hz, 1H), 5.21 - 4.97 (m, 1H), 2.29 (td, J=6.9, 13.4 Hz, 1H), 1.86 - 1.71 (m, 1H), 1.43 - 1.28 (m, 1H); LCMS(電灑) m/z 397.4 (M+H+). | D |
| 158 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.17 (br s, 1H), 12.83 (br s, 1H), 8.22 (d, J=8.4 Hz, 1H), 7.87 (s, 1H), 7.81 (d, J=8.4 Hz, 1H), 7.38 (d, J=10.2 Hz, 1H), 5.20 - 4.95 (m, 1H), 2.31 - 2.23 (m, 1H), 2.07 - 1.98 (m, 1H), 1.84 - 1.69 (m, 1H), 1.34 (tdd, J=6.4, 8.9, 12.8 Hz, 1H), 0.72 - 0.61 (m, 2H), 0.17 - 0.06 (m, 2H); LCMS(電灑) m/z 412.4 (M+H+). | D |
| 159 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.93 (s, 1H), 8.21 (d, J=8.4 Hz, 1H), 7.93 (br s, 1H), 7.78 (d, J=8.5 Hz, 1H), 5.19 - 4.96 (m, 1H), 2.31 - 2.22 (m, 1H), 1.84 - 1.70 (m, 1H), 1.39 - 1.27 (m, 1H), 1.22 (t, J=7.1 Hz, 3H); LCMS(電灑) m/z 449.3 (M+H+). | D |
| 160 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.46 (br s, 1H), 12.97 (s, 1H), 8.29 (d, J=8.3 Hz, 1H), 7.83 (s, 1H), 7.78 (d, J=8.4 Hz, 1H), 7.67 (d, J=8.8 Hz, 1H), 5.20 - 4.96 (m, 1H), 2.31 - 2.23 (m, 1H), 1.84 - 1.71 (m, 1H), 1.35 (tdd, J=6.4, 9.0, 13.0 Hz, 1H); LCMS(電灑) m/z 452.0 (M+H+). | D |
| 161 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.91 (s, 1H), 8.23 (d, J=8.4 Hz, 1H), 7.72 (s, 1H), 7.64 (d, J=8.4 Hz, 1H), 5.24 - 4.90 (m, 1H), 2.99 (s, 3H), 2.98 (s, 3H), 2.70 - 2.58 (m, 2H), 2.31 - 2.21 (m, 1H), 1.86 - 1.67 (m, 1H), 1.41 - 1.26 (m, 1H), 1.12 (t, J=7.4 Hz, 3H); LCMS(電灑) m/z 443.2 (M +H+). | D |
| 162 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (br s, 1H), 12.95 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.69 (d, J = 8.3 Hz, 1H), 5.18 - 4.96 (m, 1H), 2.67 - 2.64 (m, 2H), 2.53 (br s, 3H), 2.30 - 2.22 (m, 1H), 1.82 - 1.71 (m, 1H), 1.35 (tdd, J = 6.5, 8.8, 12.9 Hz, 1H), 1.12 (t, J = 7.4 Hz, 3H); LCMS(電灑) m/z 446.3 (M+H+). | D |
| 163 |  | 1H NMR (400MHz, CHLOROFORM-d) δ 13.46 (br s, 1H), 12.98 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.88 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 5.24 - 4.95 (m, 1H), 3.51 (br t, J = 6.9 Hz, 3H), 3.03 (br t, J = 6.6 Hz, 2H), 2.28 (br d, J = 2.6 Hz, 4H), 1.84 - 1.71 (m, 1H), 1.80 - 1.30 (m, 1H), 1.41 - 1.30 (m, 1H); LCMS(電灑) m/z 462.1 (M +H+). | D |
| 164 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.65 (br s, 1H), 13.02 (s, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.10 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 11.2 Hz, 1H), 5.19 - 4.97 (m, 1H), 3.18 (d, J = 1.0 Hz, 3H), 2.31 - 2.25 (m, 1H), 1.84 - 1.71 (m, 1H), 1.41 - 1.29 (m, 1H); LCMS(電灑) m/z 434 (M+H+). | D |
| 165 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.52 (br s, 1H), 13.33 (br s, 1H), 12.97 (s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 8.09 (s, 1H), 7.81 (s, 1H), 7.71 (br s, 1H), 7.68 (d, J = 8.4 Hz, 1H), 5.25 - 4.96 (m, 1H), 3.97 (q, J = 7.1 Hz, 2H), 3.93 - 3.87 (m, 1H), 3.78 (s, 2H), 3.70 (s, 1H), 2.72 - 2.62 (m, 3H), 2.32 - 2.23 (m, 1H), 1.84 - 1.71 (m, 1H), 1.41 - 1.31 (m, 1H), 1.21 (t, J = 7.5 Hz, 1H), 1.12 (t, J = 7.4 Hz, 3H), 1.01 (t, J = 7.1 Hz, 3H), 0.94 (t, J = 7.1 Hz, 1H); LCMS(電灑) m/z 518.3 (M +H+). | D |
| 166 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.48 ( s, 1H), 8.10 (d, J = 8.2 Hz, 1H), 7.81 (s, 1H), 7.58 (d, J = 8.2 Hz, 1H), 5.19 - 4.84 (m, 1H), 3.97 (s, 2H), 3.02 (s, 3H), 2.91 - 2.76 (m, 6H), 2.74 - 2.62 (m, 2H), 2.21 - 2.10 (m, 1H), 1.81 - 1.64 (m, 1H), 1.29 - 1.19 (m, 1H), 1.13 (t, J = 7.3 Hz, 3H); LCMS(電灑) m/z 517.1 (M+H+). | D |
| 167 |  | 1H NMR (400 MHz, DMSO-d 6) δ 7.82 ( d, J = 7.9 Hz, 1H), 7.72 (s, 1H), 7.41 (d, J = 8.2 Hz, 1H), 5.03 - 4.68 (m, 1H), 3.18 (s, 1H), 2.86 (s, 1H), 2.70 - 2.63 (m, 2H), 2.01 - 1.91 (m, 1H), 1.72 - 1.57 (m, 1H), 1.12 (t, J = 7.3 Hz, 3H), 1.05 - 0.96 (m, 1H); LCMS(電灑) m/z 503.3 (M+H+). | D |
| 168 |  | 1H NMR (400 MHz, DMSO-d 6) δ 7.82 ( d, J = 7.9 Hz, 1H), 7.72 (s, 1H), 7.41 (d, J = 8.2 Hz, 1H), 5.03 - 4.68 (m, 1H), 3.18 (s, 1H), 2.86 (s, 1H), 2.70 - 2.63 (m, 2H), 2.01 - 1.91 (m, 1H), 1.72 - 1.57 (m, 1H), 1.12 (t, J = 7.3 Hz, 3H), 1.05 - 0.96 (m, 1H); LCMS(電灑) m/z 490.3 (M+H+). | D |
| 169 |  | 1H NMR (400MHz, CHLOROFORM-d) δ 8.15 (d, J=8.3 Hz, 1H), 7.89 (br s, 1H), 7.60 (d, J=8.3 Hz, 1H), 5.10 - 4.76 (m, 1H), 3.13 (d, J=1.6 Hz, 6H), 2.35 (d, J=3.4 Hz, 3H), 2.12 - 2.01 (m, 2H), 1.49 - 1.33 (m, 1H); LCMS(電灑) m/z429.1 (M+H+). | D |
| 170 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.65 (s, 1H), 12.94 (br s, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.89 - 7.84 (m, 1H), 7.75 (d, J = 8.3 Hz, 1H), 5.20 - 4.94 (m, 1H), 2.56 (s, 3H), 2.28 (s, 3H), 2.27 - 2.23 (m, 1H), 1.84 - 1.72 (m, 1H), 1.41 - 1.30 (m, 1H); LCMS(電灑) m/z 464.0 (M +H+). | D |
| 171 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.96 (s, 1H), 12.92 (s, 1H), 8.41 (d, J = 6.5 Hz, 1H), 8.38 (d, J = 1.2 Hz, 1H), 8.29 (d, J = 8.6 Hz, 1H), 8.15 (d, J= 7.7 Hz, 1H), 5.21 - 4.94 (m, 1H), 2.24 (s, 1H), 1.88 - 1.69 (m, 1H), 1.41 - 1.29 (m, 1H); LCMS(電灑) m/z 0.887, 440.1 (M+H+). | D |
| 172 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.56 - 13.42 (m, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.90 (br s, 1H), 7.79 (d, J = 8.4 Hz, 1H), 5.20 - 4.95 (m, 1H), 3.02 (br d, J = 1.7 Hz, 6H), 2.27 (ddd, J = 2.0, 4.6, 6.7 Hz, 1H), 1.85 - 1.71 (m, 1H), 1.38 - 1.30 (m, 1H), 1.30 (s, 1H); LCMS(電灑) m/z 449.1 (M +H+). | D |
| 173 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.57 - 13.32 (m, 1H), 8.25 (dd, J = 3.0, 8.3 Hz, 1H), 7.86 (br s, 1H), 7.70 (dd, J = 2.9, 8.3 Hz, 1H), 5.22 - 4.91 (m, 1H), 2.53 (br s, 3H), 2.27 (br s, 3H), 1.83 - 1.70 (m, 1H), 1.40 - 1.27 (m, 1H), 1.21 (br d, J = 10.5 Hz, 2H); LCMS(電灑) m/z 431.07 (M +H+). | D |
| 174 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.76 (s, 1H), 12.98 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 1.3 Hz, 1H), 7.85 (d, J = 8.4 Hz, 1H), 5.21 - 4.96 (m, 1H), 2.58 (s, 3H), 2.31 - 2.25 (m, 1H), 1.84 - 1.72 (m, 1H), 1.37 - 1.30 (m, 1H); LCMS(電灑) m/z 452 (M+H+). | D |
| 175 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54 - 13.33 (m, 1H), 12.92 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.82 (s, 1H), 7.68 (d, J = 8.3 Hz, 1H), 5.19 - 4.96 (m, 1H), 4.33 (q, J = 7.0 Hz, 2H), 2.30 - 2.25 (m, 4H), 1.83 - 1.72 (m, 1H), 1.39 (t, J = 7.0 Hz, 3H), 1.36 - 1.32 (m, 1H); LCMS(電灑) m/z 430.2 (M+H+). | D |
| 176 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.90 - 13.81 (m, 1H), 12.94 (br s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.87 - 7.80 (m, 1H), 7.67 (d, J = 8.3 Hz, 1H), 5.17 - 4.95 (m, 1H), 2.76 - 2.68 (m, 2H), 2.27 - 2.19 (m, 1H), 1.82 - 1.73 (m, 1H), 1.57 - 1.42 (m, 1H), 1.15 - 1.11 (m, 3H); LCMS(電灑) m/z 418 (M +H+). | D |
| 177 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36 (s, 1H), 12.97 (s, 1H), 8.29 (d, J = 8.3 Hz, 1H), 7.92 (s, 1H), 7.74 (d, J = 8.3 Hz, 1H), 5.20 - 4.96 (m, 1H), 3.14 (s, 3H), 2.31 - 2.23 (m, 4H), 1.84 - 1.71 (m, 1H), 1.35 (tdd, J = 6.4, 8.9, 13.0 Hz, 1H); LCMS(電灑) m/z 447.9 (M +H+). | D |
| 178 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (s, 1H), 12.93 (s, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.76 (s, 1H), 7.67 - 7.65 (m, 1H), 5.21 - 4.96 (m, 1H), 4.37 - 4.31 (m, 2H), 2.68 - 2.64 (m, 2H), 2.34 - 2.33 (m, 1H), 1.81 - 1.68 (m, 1H), 1.40 (t, J = 6.8 Hz, 3H), 1.19 - 1.15 (m, 1H), 1.13 (t, J = 7.6 Hz, 3H); LCMS(電灑) m/z 444.2 (M +H+). | D |
| 179 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.27 (br s, 1H), 12.97 (s, 1H), 10.16 (s, 1H), 8.29 (d, J = 8.4 Hz, 1H), 7.91 (s, 1H), 7.85 (d, J = 8.3 Hz, 1H), 5.18 - 4.98 (m, 1H), 2.28 (ddd, J = 2.4, 4.3, 6.6 Hz, 1H), 2.19 (s, 3H), 1.82 - 1.73 (m, 1H), 1.35 (ddd, J = 2.6, 6.3, 12.9 Hz, 1H); LCMS(電灑) m/z 463.1(M +H+). | D |
| 180 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.68 (br s, 1H), 13.02 (s, 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.05 (br s, 1H), 7.87 (d, J = 8.4 Hz, 1H), 5.20 - 4.98 (m, 1H), 3.19 (s, 3H), 2.31 - 2.25 (m, 1H), 1.85 - 1.71 (m, 1H), 1.36 (tdd, J = 6.6, 8.8, 13.0 Hz, 1H); LCMS(電灑) m/z 468 (M+H+). | D |
| 181 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.96 - 12.91 (m, 2H), 9.96 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.79 (s, 1H), 7.71 (d, J = 8.3 Hz, 1H), 5.20 - 4.94 (m, 1H), 2.27 (d, J = 2.9 Hz, 3H), 2.17 (s, 4H), 1.84 - 1.71 (m, 1H), 1.42 - 1.30 (m, 1H); LCMS(電灑) m/z 442.10 (M +H+). | D |
| 182 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.19 (s, 1H), 12.99 (s, 1H), 8.31 (d, J = 8.4 Hz, 1H), 7.97 (s, 1H), 7.76 (d, J = 8.3 Hz, 1H), 5.21 - 4.95 (m, 1H), 3.51 (s, 3H), 2.33 - 2.25 (m, 4H), 1.85 - 1.71 (m, 1H), 1.41 - 1.28 (m, 1H); LCMS(電灑) m/z 463.06 (M +H+). | D |
| 183 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 - 13.24 (m, 1H), 12.99 (s, 1H), 8.30 (d, J = 8.3 Hz, 1H), 7.98 - 7.86 (m, 1H), 7.76 (d, J = 8.4 Hz, 1H),5.27 - 4.90 (m, 1H), 3.99 (s, 3H), 2.31 - 2.24 (m, 4H), 1.82 - 1.70 (m, 1H), 1.44 - 1.27 (m, 1H); LCMS(電灑) m/z 444.0 (M +H+). | D |
| 184 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.83 - 13.51 (m, 1H), 12.93 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.84 (s, 1H), 7.73 (d, J = 8.4 Hz, 1H), 5.22 - 4.93 (m, 1H), 4.51 - 4.26 (m, 2H), 2.30 - 2.28 (m, 1H), 2.06 - 2.03 (m, 1H), 1.86 - 1.73 (m, 1H), 1.64 - 1.52 (m, 1H), 1.42 (t, J = 7.0 Hz, 3H), 1.33 (m, J = 6.7, 14.0 Hz, 1H); LCMS(電灑) m/z 462.2 (M+H+). | D |
| 185 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.48 (s, 1H), 13.03 (s, 1H), 8.34 (d, J = 8.3 Hz, 1H), 8.09 (d, J = 1.3 Hz, 1H), 7.89 (d, J = 8.3 Hz, 1H), 5.20 - 4.98 (m, 1H), 3.57 (s, 3H), 2.31 - 2.25 (m, 1H), 1.85 - 1.73 (m, 1H), 1.41 - 1.31 (m, 1H); LCMS(電灑) m/z 484 (M+H+). | D |
| 186 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.92 - 13.91 (m, 1H), 13.91 - 13.90 (m, 1H), 13.86 (br s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.93 (br d, J = 2.7 Hz, 1H), 7.68 (d, J = 8.3 Hz, 1H), 5.17 - 4.95 (m, 1H), 2.32 - 2.31 (m, 1H), 2.31 (d, J = 2.9 Hz, 2H), 2.26 (dt, J = 2.2, 4.5 Hz, 1H), 1.84 - 1.73 (m, 1H), 1.32 - 1.25 (m, 1H); LCMS(電灑) m/z 404.2 (M +H+). | D |
| 187 |  | 1H NMR (400 MHz, DMSO-d 6) δ 8.42 (d, J = 8.3 Hz, 1H), 8.14 (d, J = 3.2 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 5.38 - 5.15 (m, 1H), 2.71 - 2.70 (m, 3H), 2.45 (br s, 1H), 2.03 - 1.89 (m, 1H), 1.41 (s, 1H); LCMS(電灑) m/z 436.1 (M +H+). | D |
| 188 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.25 (d, J = 8.4 Hz, 1H), 7.84 (s, 1H), 7.71 (d, J = 8.3 Hz, 1H), 5.04 (dt, J = 3.9, 6.2 Hz, 1H), 2.32 (d, J = 3.3 Hz, 3H), 2.24 -2.16 (m, 1H), 1.98 - 1.84 (m, 1H), 1.34 - 1.29 (m, 1H); LCMS(電灑) m/z 429.9 (M+H+). | D |
| 189 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.34 (s, 1H), 8.31 - 8.28 (m, 1H), 8.05 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 5.17 - 4.98 (m, 1H), 3.25 (s, 3H), 2.28 (ddd, J = 1.8, 4.7, 6.8 Hz, 1H), 1.83 (s, 3H), 1.75 (dt, J = 3.8, 6.9 Hz, 1H), 1.38 - 1.32 (m, 1H); LCMS(電灑) m/z 477.0 (M +H+). | D |
| 190 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.61 (br s, 1H), 12.99 - 12.91 (m, 1H), 8.31 - 8.24 (m, 1H), 7.94 - 7.88 (m, 1H), 7.77 - 7.70 (m, 1H), 5.23 - 4.96 (m, 1H), 3.22 (s, 3H), 2.30 (d, J = 2.8 Hz, 3H), 2.28 - 2.23 (m, 1H), 1.80 (s, 3H), 1.77 - 1.70 (m, 1H), 1.41 - 1.29 (m, 1H); LCMS(電灑) m/z 456.12 (M +H+). | D |
| 191 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.90 (br , 2H), 8.20 (d, J = 8.0 Hz, 1H), 7.83 (s, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.49 (s, 1H), 5.15 - 4.98 (m, 1H), 5.04 (d, J = 5.2 Hz, 1H), 3.24 (s, 3H), 2.32-2.26 (m, 2H), 1.80-1.73 (m, 1H), 1.35 - 1.23 (m, 1H); LCMS (電灑) m/z 450.1 (M+H)+. | D |
| 192 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.94 (s, 1H), 12.88 (s, 1H), 8.37 (s, 1H), 8.22 (d, J = 8.4 Hz, 1H), 7.90 (s, 1H), 7.77 (d, J = 8.4 Hz, 1H), 5.15 - 4.98 (m, 1H), 2.60 (d, J = 5.2 Hz, 3H), 2.18-2.13 (m, 1H), 1.71 - 1.63 (m, 1H), 1.35 - 1.12 (m, 10H); LCMS (電灑) m/z 550.1 (M+H)+. | D |
| 193 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.87 - 13.62 (m, 1H), 8.29 (d, J = 8.5 Hz, 1H), 7.98 (s, 1H), 7.86 (d, J = 8.5 Hz, 1H), 5.18 - 4.95 (m, 1H), 3.12 (s, 3H), 2.93 (s, 3H), 2.27 (ddd, J = 2.0, 4.6, 6.7 Hz, 1H), 1.82 - 1.71 (m, 1H), 1.34 (ddd, J = 2.6, 6.3, 13.0 Hz, 1H); LCMS(電灑) m/z 476.9 (M +H+). | D |
| 194 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36 (br s, 1H), 12.90 (br s, 1H), 8.21 (d, J = 8.8 Hz, 1H), 7.77 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 5.19 - 4.95 (m, 1H), 2.99 (s, 6H), 2.27 (s, 4H), 1.84 - 1.70 (m, 1H), 1.40 - 1.28 (m, 1H); LCMS(電灑) m/z 461 (M+H+). | D |
| 195 |  | 1H NMR (400 MHz, DMSO-d 6) δ 8.65 (br d, J = 3.3 Hz, 1H), 8.19 - 8.12 (m, 1H), 7.95 (s, 1H), 7.77 (d, J = 8.3 Hz, 1H), 5.17 - 4.89 (m, 1H), 2.91 (d, J = 4.5 Hz, 3H), 2.23 - 2.14 (m, 1H), 1.85 - 1.63 (m, 1H), 1.35 - 1.17 (m, 1H); LCMS(電灑) m/z 462.9 (M +H+). | D |
| 196 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.53 - 13.38 (m, 1H), 13.59 - 13.37 (m, 1H), 8.31 - 8.23 (m, 1H), 7.96 - 7.87 (m, 1H), 7.85- 7.76 (m, 1H), 5.21 - 4.96 (m, 1H), 3.31 (br s, 2H), 3.09 - 2.92 (m, 3H), 2.35 - 2.23 (m, 1H), 1.87 - 1.72 (m, 1H), 1.42 - 1.30 (m, 1H), 1.14 - 1.05 (m, 3H); LCMS(電灑) m/z 463.7 (M+H+). | D |
| 197 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.48 - 13.33 (m, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.86 (s, 1H), 7.72 (d, J = 8.4 Hz, 1H), 5.19 - 4.93 (m, 1H), 3.12 (s, 3H), 2.92 (s, 3H), 2.28 (d, J = 2.9 Hz, 3H), 2.27 - 2.22 (m, 1H), 1.82 - 1.69 (m, 1H), 1.39 - 1.28 (m, 1H); LCMS(電灑) m/z 457.1 (M+H+). | D |
| 198 |  | 1H NMR (400 MHz, DMSO-d 6) δ 8.35 (s, 1H),8.22 (d, J = 8.4 Hz, 1H), 7.96 (s, 1H), 7.65 (d, J = 8.4 Hz, 1H), 5.17 - 4.91 (m, 1H), 2.30 - 2.19 (m, 1H), 1.83 - 1.69 (m, 1H),1.39 - 1.28 (m, 1H); LCMS(電灑) m/z 474.1 (M+H+). | D |
| 199 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.01 - 12.83 (m, 1H), 8.30 - 8.14 (m, 1H),7.98 - 7.94 (m, 1H), 7.80 (s, 1H), 7.71 - 7.59 (m, 1H),5.28 - 4.88 (m, 1H), 2.49 - 2.48 (m, 3H),2.27 - 2.24 (m, 4H), 1.83 - 1.72 (m, 1H), 1.39 - 1.30 (m, 1H); LCMS(電灑) m/z 400.0 (M +H+). | D |
| 200 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (s, 1H), 13.03 - 12.78 (m, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.74 - 7.61 (m, 2H), 5.20 - 4.94 (m, 1H), 3.23 (br d, J = 7.1 Hz, 2H), 2.95 (d, J = 1.8 Hz, 3H), 2.63 (br d, J = 5.8 Hz, 2H), 2.29 - 2.24 (m, 1H), 1.83 - 1.71 (m, 1H), 1.40 - 1.29 (m, 1H), 1.12 (t, J = 7.4 Hz, 3H), 1.06 (t, J = 7.1 Hz, 3H); LCMS(電灑) m/z 457.0 (M +H+). | D |
| 201 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.19 (br s, 1H), 12.89 (br s, 1H), 8.24 (d, J = 8.5 Hz, 1H), 8.15 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.53 (d, J = 10.5 Hz, 1H), 5.19 - 4.96 (m, 1H), 3.91 (q, J = 7.0 Hz, 2H), 2.31 - 2.23 (m, 1H), 1.84 - 1.72 (m, 1H), 1.39 - 1.30 (m, 1H), 1.15 (t, J = 6.9 Hz, 3H); LCMS(電灑) m/z 416.0 (M+H+). | D |
| 202 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.20 - 13.00 (m, 1H), 12.95 - 12.86 (m, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.80 (s, 1H), 7.67 (d, J = 8.4 Hz, 1H), 6.98 - 6.89 (m, 1H), 5.21 - 4.94 (m, 1H), 4.09 (br t, J = 5.9 Hz, 2H), 3.38 - 3.33 (m, 2H), 3.04 - 2.98 (m, 3H), 2.57 - 2.52 (m, 3H), 2.28 (br dd, J = 2.1, 4.4 Hz, 1H), 2.26 - 2.26 (m, 1H), 2.25 (d, J = 3.1 Hz, 3H), 1.83 - 1.71 (m, 1H), 1.39 - 1.30 (m, 1H); LCMS(電灑) m/z 516.1 (M +H+). | D |
| 203 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.13 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.77 (s, 1H), 7.68 (d, J = 8.3 Hz, 1H), 5.23 - 4.94 (m, 1H), 3.22 (q, J = 6.9 Hz, 2H), 2.95 (d, J = 2.1 Hz, 3H), 2.30 - 2.27 (m, 1H), 2.25 (d, J = 3.2 Hz, 3H), 1.87 - 1.68 (m, 1H), 1.35 (tdd, J = 6.5, 8.7, 13.1 Hz, 1H), 1.06 (t, J = 7.2 Hz, 3H); LCMS(電灑) m/z 442.14 (M +H+). | D |
| 204 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.27 - 13.06 (m, 1H), 8.21 (br d, J = 8.1 Hz, 1H), 7.78 (br s, 1H), 7.66 (br d, J = 8.4 Hz, 1H), 5.19 - 4.95 (m, 1H), 4.91 (br s, 1H), 3.65 - 3.55 (m, 2H), 3.27 - 3.14 (m, 2H), 3.04 - 2.94 (m, 3H),2.28 - 2.19 (m, 4H), 1.82 - 1.68 (m, 1H), 1.38 - 1.26 (m, 1H); LCMS(電灑) m/z 459.1 (M +H+). | D |
| 205 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.63 (br s, 1H), 8.27 (d, J=8.3 Hz, 1H), 7.99 (s, 1H), 7.74 (d, J=8.3 Hz, 1H), 5.19 - 4.95 (m, 1H), 2.29 (d, J=2.9 Hz, 3H), 2.28 - 2.22 (m, 1H), 1.84 - 1.70 (m, 1H), 1.39 - 1.27 (m, 1H); LCMS(電灑) m/z 454.2 (M+H+). | D |
| 206 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.24 (br d, J = 2.9 Hz, 1H), 8.50 - 8.44 (m, 1H), 8.18 (d, J = 8.3 Hz, 1H), 7.84 (s, 1H), 7.67 (d, J = 8.2 Hz, 1H), 5.17 - 4.89 (m, 1H), 2.91 (d, J = 4.4 Hz, 3H), 2.29 (d, J = 2.8 Hz, 3H), 2.24 - 2.18 (m, 1H), 1.83 - 1.67 (m, 1H), 1.35 - 1.21 (m, 1H); LCMS(電灑) m/z 442.10 (M +H+). | D |
| 207 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.86 - 13.56 (m, 1H), 12.95 (s, 1H), 8.24 (d, J = 8.3 Hz, 1H), 7.73 (s, 1H), 7.62 (d, J = 8.3 Hz, 1H), 5.19 - 4.96 (m, 1H), 3.03 (d, J = 2.2 Hz, 6H), 2.32 - 2.21 (m, 1H), 1.83 - 1.71 (m, 1H), 1.41 - 1.31 (m, 1H); LCMS(電灑) m/z 483.2 (M+H+). | D |
| 208 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.23 (d, J=8.4 Hz, 1H), 7.98 (d, J=3.3 Hz, 1H), 7.82 (d, J=8.4 Hz, 1H), 5.04 (dt, J=3.9, 6.2 Hz, 1H), 2.20 (dtd, J=4.3, 6.9, 9.1 Hz, 1H), 1.95 - 1.84 (m, 1H), 1.37 - 1.29 (m, 1H); LCMS(電灑) m/z 424.1 (M +H+). | D |
| 209 |  | 1H NMR (400 MHz, DMSO-d 6) δ 1.27-1.40 (m, 1 H), 1.71-1.83 (m, 1 H), 2.27 (br s, 1 H), 4.95-5.19 (m, 1 H), 7.51 (s, 1 H), 7.65 (s, 1 H), 7.78 (br s, 1 H), 7.87 (br d, J=8.68 Hz, 1 H), 8.05 (br s, 1 H), 8.21-8.38 (m, 1 H), 12.77-13.42 (m, 1 H), 13.77-14.05 (m, 1 H); LCMS(電灑) m/z 456.1 (M+H+). | D |
| 210 |  | 1H NMR (400 MHz, DMSO-d 6) δ 1.12 (br t, J=7.40 Hz, 3 H), 1.27-1.42 (m, 1 H), 1.68-1.85 (m, 1 H), 2.22-2.31 (m, 1 H), 2.68 (br d, J=7.28 Hz, 2 H), 4.90-5.23 (m, 1 H), 7.73 (d, J=8.41 Hz, 1 H), 7.93 (br s, 1 H), 8.30 (d, J=8.28 Hz, 1 H), 12.60-13.33 (m, 1 H), 13.48-13.91 (m, 1 H); LCMS(電灑) m/z 468.2 (M+H+). | D |
| 211 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.79 - 13.40 (m, 1H), 13.10 - 12.67 (m, 1H), 8.75 - 8.46 (m, 1H), 8.39 - 8.10 (m, 1H), 8.01 - 7.71 (m, 1H), 5.24 - 4.92 (m, 1H), 2.65 - 2.55 (m, 3H), 2.32 - 2.22 (m, 1H), 2.35 - 2.22 (m, 2H), 1.88 - 1.63 (m, 1H), 1.49 - 1.19 (m, 2H); LCMS(電灑) m/z 420.0 (M +H+). | D |
| 212 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 - 13.72 (m, 1 H) 12.88 (s, 1 H) 8.74 (s, 1 H) 8.13 - 8.21 (m, 2 H) 7.77 (d, J=7.75 Hz, 1 H) 7.35 (d, J=7.75 Hz, 1 H) 4.92 - 5.19 (m, 1 H) 3.17 (s, 1 H) 2.65 (s, 3 H) 2.23 - 2.31 (m, 1 H) 1.74 - 1.84 (m, 2 H) 1.31 - 1.39 (m, 1 H); LCMS(電灑) m/z 400.0 (M+H+). | D |
| 213 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.93 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.96 (s, 1H), 7.74 (d, J = 8.3 Hz, 1H), 5.25 - 4.89 (m, 1H), 2.31 (d, J = 2.8 Hz, 3H), 2.29 - 2.22 (m, 1H), 1.84 - 1.70 (m, 1H), 1.29-1.36 (m, J = 2.6, 6.2, 12.8 Hz, 1H); LCMS(電灑) m/z 470.2 (M+H+). | D |
| 214 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.27 (br s, 1H), 13.01 - 12.74 (m, 1H), 8.68 (br s, 1H), 8.55 (d, J = 8.6 Hz, 1H), 8.22 (d, J = 8.5 Hz, 1H), 8.15 (q, J = 8.6 Hz, 2H), 7.61 (d, J = 14.3 Hz, 1H), 5.18 - 4.96 (m, 1H), 2.99 (br s, 6H), 2.30 - 2.23 (m, 1H), 1.83- 1.72 (m, 1H), 1.38 - 1.31 (m, 1H); LCMS(電灑) m/z 415.2 (M +H+). | D |
| 215 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.03 (s, 1H), 12.97 (s, 1H), 8.82 (s, 1H), 8.26 (s, 2H), 7.90 (d, J = 12.0 Hz, 1H), 5.24 - 4.94 (m, 1H), 2.28 (ddd, J = 2.0, 4.6, 6.7 Hz, 1H), 1.87 - 1.70 (m, 1H), 1.32-1.36 (m, J = 2.6, 6.2, 12.7 Hz, 1H); LCMS(電灑) m/z 456.2 (M+H+). | D |
| 216 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.30 - 12.94 (m, 1H), 8.73 - 8.65 (m, 1H), 8.15 - 8.08 (m, 1H), 8.07 - 8.01 (m, 1H), 7.66 (d, J = 7.9 Hz, 1H), 6.82 - 6.73 (m, 1H), 5.29 - 4.92 (m, 1H), 3.13 - 2.82 (m, 6H), 2.29 - 2.18 (m, 1H), 2.07 (s, 1H), 1.84 - 1.69 (m, 1H), 1.39 - 1.25 (m, 1H); LCMS(電灑) m/z 397.1 (M +H+). | D |
| 217 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.94 - 13.07 (m, 1H), 8.24 (d, J =8.3 Hz, 1H), 7.92 (s, 1H), 7.74 - 7.44 (m, 2H), 5.18 - 4.91 (m, 1H), 2.27 (d, J = 2.6 Hz, 3H), 2.26 - 2.22 (m, 1H), 1.82 - 1.71 (m,1H), 1.37 - 1.28 (m, 1H); LCMS(電灑) m/z 436.1 (M+H+). | D |
| 218 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.33 (br s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.77 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 5.19 - 4.95 (m, 1H), 3.25 (br d, J = 7.7 Hz, 2H), 2.97 (d, J = 1.6 Hz, 3H), 2.26 (s, 3H), 1.85 - 1.70 (m, 1H), 1.40 - 1.21 (m, 2H), 1.10 - 1.04 (m, 3H); LCMS(電灑) m/z 475 (M+H+). | D |
| 219 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.32 (s, 1H), 13.04 (s, 1H), 9.13 (s, 1H), 8.31 (s, 1H), 7.79 (s, 1H), 7.52 (d, J = 9.3 Hz, 1H), 5.23-4.94 (m, 1H), 2.35 - 2.17 (m, 4H), 1.86-1.68 (m, 1H), 1.41-1.29 (m, 1H); LCMS(電灑) m/z 418.0 (M +H+). | D |
| 220 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.60 (s, 1H), 13.10 (s, 1H), 9.12 (s, 1H), 8.53 (s, 1H), 8.14 (s, 1H), 7.63 (d, J = 11.5 Hz, 1H), 5.19-4.96 (m, 1H), 3.17 (s, 3H), 2.29 - 2.21 (m, 1H), 1.86-1.68 (m, 1H), 1.39 - 1.29 (m, 1H); LCMS(電灑) m/z 434.0 (M +H+). | D |
| 221 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.77 (s, 1H), 9.70 (s, 1H), 9.00 (s, 1H), 8.66 (d, J = 9.2 Hz, 1H), 8.59 (s, 1H), 8.55 (d, J = 9.2 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.8 Hz, 1H), 5.91 ~ 5.71 (m, 1H), 3.11 (s, 3H), 3.05 ~ 3.00 (m, 1H), 2.54 ~ 2.48 (m, 1H), 2.07 ~ 2.03 (m, 1H); LCMS (電灑) m/z 350.0 (M+H)+. | E |
| 222 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.23 (s, 1H), 11.01 (s, 1H), 8.93 (s, 1H), 8.17 (s, 1H), 7.59 ~ 7.51 (m, 3H), 7.42 (t, J = 7.8 Hz, 1H), 7.26 (d, J = 6.4 Hz, 1H), 5.00 ~ 4.79 (m, 1H), 2.13 ~ 2.10 (m, 1H), 1.67 ~ 1.60 (m, 1H), 1.17 ~ 1.09 (m, 1H); LCMS (電灑) m/z 335.9 (M+H)+. | E |
| 223 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.92 (s, 1H), 8.13 (s, 1H), 7.99 - 7.91 (m, 3H), 7.68 (dd, J=1.0, 8.9 Hz, 1H), 7.58 (d, J=8.9 Hz, 1H), 1.95 - 1.87 (m, 1H), 1.12 - 1.07 (m, 2H), 1.05 - 0.98 (m, 2H); LCMS (電灑) m/z 352.0 (M+H)+. | F |
| 224 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.98 (s, 1H), 8.17 - 8.09 (m, 3H), 7.94 (d, J=9.2 Hz, 1H), 7.71 (d, J=9.2 Hz, 1H), 7.54 - 7.48 (m, 1H), 3.90 (s, 3H), 1.94 - 1.85 (m, 1H), 1.12 - 1.06 (m, 2H), 1.05 - 0.99 (m, 2H); LCMS (電灑) m/z 348.0 (M+H)+. | F |
| 225 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.76 (s, 1H), 7.88 - 7.83 (m, 2H), 7.75 (dd, J=1.5, 9.2 Hz, 1H), 7.66 (dd, J=0.8, 8.9 Hz, 1H), 7.36 (d, J=8.9 Hz, 1H), 1.96 - 1.88 (m, 1H), 1.09 - 1.04 (m, 2H), 1.02 - 0.95 (m, 2H); LCMS (電灑) m/z 333.2 | F |
| 226 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.43 (br s, 1H), 8.80 (s, 1H), 8.16 (s, 1H), 7.93 (s, 1H), 7.84 - 7.76 (m, 2H), 7.69 (d, J=9.4 Hz, 1H), 7.45 (br d, J=8.9 Hz, 1H), 1.97 (quin, J=6.2 Hz, 1H), 0.86 (d, J=6.0 Hz, 4H); LCMS (電灑) m/z 386.1 (M+H)+. | F |
| 227 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.40 (br s, 1H), 8.83 (s, 1H), 8.14 (s, 1H), 7.75 (d, J=9.0 Hz, 1H), 7.68 (s, 1H), 7.61 (d, J=9.0 Hz, 1H), 7.37 (d, J=10.9 Hz, 1H), 6.90 - 5.46 (m, 6H), 1.94 (quin, J=6.2 Hz, 1H), 0.95 - 0.82 (m, 4H); LCMS (電灑) m/z 351.2 (M+H)+. | F |
| 228 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.56 - 8.53 (m, 1H), 8.11 (s, 1H), 7.82 (s, 1H), 7.68 (d, J=8.9 Hz, 1H), 7.58 - 7.50 (m, 2H), 7.38 (dd, J=1.7, 9.2 Hz, 1H), 1.97 - 1.88 (m, 1H), 1.02 - 0.97 (m, 2H), 0.93 - 0.88 (m, 2H); LCMS (電灑) m/z 397.9 (M+H)+. | F |
| 229 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.82 (br s, 1H), 7.89 (br d, J=8.8 Hz, 1H), 7.82 - 7.73 (m, 3H), 7.45 (d, J=8.9 Hz, 1H), 2.98 (s, 3H), 1.98 - 1.86 (m, 1H), 1.12 - 0.95 (m, 4H); LCMS (電灑) m/z 347.0 (M+H)+. | F |
| 230 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.60 - 8.57 (m, 1H), 8.09 (s, 1H), 7.87 (s, 1H), 7.58 - 7.49 (m, 3H), 7.48 - 7.44 (m, 1H), 2.62 (s, 6H), 1.97 - 1.89 (m, 1H), 1.03 - 0.97 (m, 2H), 0.94 - 0.88 (m, 2H); LCMS (電灑) m/z 361.2 (M+H)+. | F |
| 231 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (br s, 1H), 11.05 (s, 1H), 8.78 (s, 1H), 8.14 (s, 1H), 7.92 (s, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.57 (d, J=9.2 Hz, 1H), 7.32 (dd, J=1.7, 9.2 Hz, 1H), 2.05 - 1.86 (m, 1H), 0.85 - 0.79 (m, 4H); LCMS (電灑) m/z 414.1 (M+H)+. | G |
| 232 |  | 1H NMR (400MHz, METHANOL-d 4) δ 9.17 (s, 1H), 8.22 (s, 1H), 8.21 - 8.18 (m, 1H), 8.06 (d, J=9.3 Hz, 1H), 7.84 (s, 2H), 1.94 - 1.87 (m, 1H), 1.14 - 1.09 (m, 2H), 1.07 - 1.01 (m, 2H); LCMS (電灑) m/z 343.0 (M+H)+. | F |
| 233 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.91 (s, 1H), 8.10 (s, 1H), 8.07 - 8.03 (m, 1H), 8.00 - 7.96 (m, 1H), 7.91 (s, 1H), 7.72 - 7.65 (m, 2H), 4.61 (s, 2H), 3.61 (s, 1H), 1.93 - 1.86 (m, 1H), 1.13 - 1.08 (m, 2H), 1.07 - 1.01 (m, 2H); LCMS (電灑) m/z 348.2 (M+H)+. | F |
| 234 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.82 (s, 1H), 8.10 (s, 1H), 8.01 - 7.95 (m, 1H), 7.95 - 7.89 (m, 1H), 7.78 (s, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.50 (d, J=8.7 Hz, 1H), 2.69 (q, J=7.5 Hz, 2H), 1.93 - 1.85 (m, 1H), 1.19 (t, J=7.5 Hz, 3H), 1.13 - 1.07 (m, 2H), 1.07 - 0.98 (m, 2H); LCMS (電灑) m/z 346.2 (M+H)+. | F |
| 235 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.82 (br s, 1H), 8.90 (s, 1H), 8.19 (s, 1H), 7.91 (d, J=0.6 Hz, 1H), 7.83 (d, J=9.2 Hz, 1H), 7.63 (br d, J=9.2 Hz, 1H), 7.50 (d, J=11.4 Hz, 1H), 6.54 (dd, J=11.9, 17.9 Hz, 1H), 5.63 (br d, J=17.9 Hz, 1H), 5.42 (br d, J=11.6 Hz, 1H), 2.06 - 1.94 (m, 1H), 0.95 - 0.85 (m, 4H); LCMS (電灑) m/z 362.1 (M+H)+. | F |
| 236 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.46 (br s, 1H), 8.82 (s, 1H), 8.20 (s, 1H), 7.94 (s, 1H), 7.85 - 7.76 (m, 2H), 7.71 (br d, J=9.2 Hz, 1H), 7.47 (br d, J=8.6 Hz, 1H), 5.11 - 4.85 (m, 1H), 2.20 (td, J=6.9, 13.9 Hz, 1H), 1.77 - 1.63 (m, 1H), 1.31 - 1.16 (m, 1H), 1.31 - 1.16 (m, 1H); LCMS (電灑) m/z 403.8 (M+H)+. | F |
| 237 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.40 (s, 1H), 11.05 (s, 1H), 8.77 (s, 1H), 8.16 (s, 1H), 7.91 (s, 1H), 7.62 (d, J=9.7 Hz, 1H), 7.58 - 7.48 (m, 2H), 7.34 (dd, J=1.7, 9.2 Hz, 1H), 5.04 - 4.80 (m, 1H), 2.20 - 2.10 (m, 1H), 1.73 - 1.59 (m, 1H), 1.23 - 1.10 (m, 1H); LCMS (電灑) m/z 370.1 (M+H)+. | F |
| 238 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.49 (br s, 1H), 8.88 (br s, 1H), 8.20 (s, 1H), 7.90 (s, 1H), 7.73 (br d, J=9.2 Hz, 1H), 7.69 - 7.64 (m, 1H), 7.63 - 7.53 (m, 2H), 5.11 - 4.86 (m, 1H), 2.19 (br s, 1H), 1.77 - 1.62 (m, 1H), 1.22 (br d, J=2.9 Hz, 1H); LCMS (電灑) m/z 415.8 (M+H)+. | F |
| 239 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.69 (br s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 8.04 (s, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.77 (br d, J=9.0 Hz, 1H), 7.71 (d, J=8.8 Hz, 1H), 7.59 (br d, J=8.8 Hz, 1H), 2.40 (s, 3H), 2.03 - 1.95 (m, 1H), 0.95 - 0.87 (m, 4H); LCMS (電灑) m/z 359.9 (M+H)+. | F |
| 240 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.27 (s, 1H), 8.99 (s, 1H), 8.21 (s, 1H), 7.98 (d, J=9.2 Hz, 1H), 7.85 (dd, J=1.5, 9.1 Hz, 1H), 7.69 (dd, J=1.0, 8.1 Hz, 2H), 6.23-5.16 (m, 6H), 2.13-2.00 (m, 1H), 1.04-0.87 (m, 4H); LCMS (電灑) m/z 367.0 (M+H+) | F |
| 241 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.09 (br s, 1H), 9.04 (s, 1H), 8.22 (s, 1H), 7.97 - 7.86 (m, 3H), 7.41 (d, J=10.5 Hz, 1H), 2.07 - 2.00 (m, 1H), 1.99 - 1.91 (m, 1H), 1.99 - 1.91 (m, 1H), 0.97 - 0.87 (m, 4H), 0.78 - 0.68 (m, 2H), 0.26 (br d, J=4.5 Hz, 2H); LCMS (電灑) m/z 376.1 (M+H+) | F |
| 242 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.50 (br s, 1H), 11.17 (s, 1H), 8.68 (d, J=7.2 Hz, 1H), 7.92 (s, 1H), 7.79 (d, J=1.0 Hz, 1H), 7.68 (dd, J=0.9, 9.0 Hz, 1H), 6.97 (s, 1H), 6.96 (d, J=2.0 Hz, 1H), 6.96 - 6.93 (m, 1H), 2.13-2.00 (m, 1H), 1.04-0.87 (m, 4H); LCMS (電灑)m/z 370.8 (M+H+) | F |
| 243 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.91 - 11.45 (m, 1H), 9.05 - 8.93 (m, 1H), 8.24 (br s, 1H), 8.00 (s, 1H), 7.87 - 7.59 (m, 3H), 5.07 (br s, 1H), 4.91 (br s, 1H), 2.22 (br s, 1H), 1.79 - 1.63 (m, 1H), 1.23 (br s, 1H); LCMS (電灑) m/z 388.0 (M+H+) | F |
| 244 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.99 (br s, 1H), 8.99 (s, 1H), 8.23 (s, 1H), 7.95 - 7.85 (m, 2H), 7.82 (d, J=0.9 Hz, 1H), 7.55 (d, J=8.7 Hz, 1H), 7.08 (d, J=8.7 Hz, 1H), 2.07 - 1.89 (m, 2H), 0.98 - 0.90 (m, 4H), 0.87 - 0.81 (m, 2H), 0.69 - 0.63 (m, 2H); LCMS (電灑) m/z 358.0 (M+H+) | F |
| 245 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.27 (br s, 1H), 8.78 (s, 1H), 8.14 (s, 1H), 7.82 (s, 1H), 7.67 (br d, J=9.0 Hz, 1H), 7.46 (br d, J=9.0 Hz, 1H), 7.40 (br d, J=9.8 Hz, 1H), 2.21 (br d, J=1.2 Hz, 3H), 2.00 - 1.88 (m, 1H), 0.86 (br d, J=5.7 Hz, 4H); LCMS (電灑) m/z 350.2 (M+H+) | F |
| 246 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.30 (s, 1H), 8.73 (s, 1H), 8.15 (s, 1H), 7.71 - 7.65 (m, 2H), 7.40 (br d, J=11.8 Hz, 2H), 3.04 (td, J=7.0, 14.1 Hz, 1H), 1.98-1.92 (m, 1H), 1.28 (dd, J=6.9, 17.4 Hz, 6H), 0.87 (d, J=6.1 Hz, 4H); LCMS (電灑) m/z 378.1 (M+H+) | F |
| 247 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.22 (s, 1H), 8.99 (s, 1H), 8.24 (s, 1H), 7.98-7.91 (m, 1H), 7.90-7.84 (m, 2H), 7.71-7.65 (m, 1H), 7.62-7.57 (m, 1H), 2.40 (s, 3H), 2.11-1.99 (m, 1H), 1.05-0.87 (m, 4H); LCMS (電灑) m/z 364.1 (M+H+) | F |
| 248 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.18 (s, 1H), 8.95 (s, 1H), 8.24 (s, 1H), 7.95 (d, J=9.0 Hz, 1H), 7.81 - 7.74 (m, 2H), 7.46 (d, J=10.3 Hz, 1H), 2.58 (q, J=6.8 Hz, 2H), 2.09 - 2.00 (m, 1H), 1.09 (t, J=7.3 Hz, 3H), 0.98 - 0.87 (m, 4H); LCMS (電灑) m/z 364.1 (M+H+) | F |
| 249 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.53 (br s, 1H), 11.13 (s, 1H), 8.72 (s, 1H), 8.15 (s, 1H), 7.97 (s, 1H), 7.78 - 7.74 (m, 1H), 7.73 - 7.69 (m, 1H), 7.63 (d, J=9.2 Hz, 1H), 7.34 (d, J=9.0 Hz, 1H), 7.11 - 6.80 (m, 1H), 2.00 - 1.91 (m, 1H), 0.87 - 0.81 (m, 4H); LCMS (電灑) m/z 368.2 (M+H+) | F |
| 250 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.16 (s, 1H), 11.06 (s, 1H), 8.70 (s, 1H), 8.15 (s, 1H), 7.80 (s, 1H), 7.56 (d, J=9.2 Hz, 1H), 7.38 (d, J=9.8 Hz, 1H), 7.29 (dd, J=1.7, 9.2 Hz, 1H), 5.09 - 4.77 (m, 1H), 2.22 (d, J=2.4 Hz, 3H), 2.18 - 2.11 (m, 1H), 1.75 - 1.58 (m, 1H), 1.24 - 1.06 (m, 1H); LCMS (電灑) m/z 368.1 (M+H+) | F |
| 251 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.92 (br s, 1H), 8.99 (s, 1H), 8.21 (s, 1H), 7.96-7.81 (m, 3H), 7.46 (d, J=9.9 Hz, 1H), 4.43 (s, 2H), 2.07-1.96 (m, 1H), 0.96-0.87 (m, 4H); LCMS (電灑) m/z 366.1 (M+H+) | F |
| 252 |  | 1H NMR (400MHz, METHANOL-d 4) δ 9.03 (s, 1H), 8.18 - 8.14 (m, 1H), 8.05 (s, 1H), 7.99 (d, J=9.2 Hz, 1H), 7.49 (d, J=10.6 Hz, 1H), 3.77 (s, 3H), 1.95 - 1.82 (m, 1H), 1.15 - 1.07 (m, 2H), 1.06 - 1.00 (m, 2H); LCMS (電灑) m/z 366.1 (M+H+) | F |
| 253 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.64 (s, 1H), 11.16 (s, 1H), 8.76 (s, 1H), 8.19 (s, 1H), 7.98 (s, 1H), 7.66 - 7.57 (m, 2H), 7.29 (dd, J=1.8, 9.1 Hz, 1H), 7.13 - 6.78 (m, 1H), 5.07 - 4.80 (m, 1H), 2.16 (td, J=6.9, 13.9 Hz, 1H), 1.74 - 1.61 (m, 1H), 1.24 - 1.13 (m, 1H); LCMS (電灑) m/z 404.0 (M+H+) | F |
| 254 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.50 (s, 1H), 11.11 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.93 (s, 1H), 7.65 (d, J=8.8Hz, 1H), 7.57 (d, J=9.2Hz, 1H), 7.32 (dd, J=1.6, 7.6Hz, 1H), 5.02 (m, 0.5H), 4.85 (m, 0.5H), 2.16 (m, 1H), 1.66 (m, 1H), 1.16 (m, 1H), LCMS (電灑) m/z 433.00 (M+H)+. | F |
| 255 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.59 (br s, 1H), 11.04 (s, 1H), 8.72 (s, 1H), 8.15 (s, 1H), 7.97 (s, 1H), 7.62 - 7.56 (m, 2H), 7.23 (dd, J=1.7, 9.1 Hz, 1H), 7.11 - 6.80 (m, 1H), 2.01 - 1.92 (m, 1H), 0.85 - 0.79 (m, 4H); LCMS (電灑) m/z 386.1 (M+H+) | F |
| 256 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.14 (s, 1H), 11.13 (s, 1H), 8.87 - 8.83 (m, 1H), 8.19 (s, 1H), 8.15 (br s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.40 (dd, J = 1.8, 9.2 Hz, 1H), 5.04 - 4.83 (m, 1H), 2.19 - 2.13 (m, 1H), 1.72 - 1.62 (m, 1H), 1.23 - 1.15 (m, 1H); LCMS (電灑) m/z 422.1 (M+H)+. | F |
| 257 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36 (s, 1H), 11.19 (br s, 1H), 8.72 (s, 1H), 8.16 (s, 1H), 7.80 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.37 (br d, J=9.2 Hz, 1H), 5.10 - 4.79 (m, 1H), 2.48 (d, J=1.7 Hz, 3H), 2.21 (d, J=2.8 Hz, 3H), 2.18 - 2.10 (m, 1H), 1.75 - 1.61 (m, 1H), 1.27 - 1.10 (m, 1H); LCMS (電灑) m/z 382.4 (M+H)+. | F |
| 258 |  | 1H NMR (400 MHz, DMSO-d 6)) δ 13.55 (br s, 1H), 11.21 (s, 1H), 8.80 (s, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.43 (d, J=9.2 Hz, 1H), 5.08 - 4.77 (m, 1H), 3.01 (s, 3H), 3.00 (s, 3H), 2.16 (td, J=7.0, 13.8 Hz, 1H), 1.76 - 1.57 (m, 1H), 1.27 - 1.11 (m, 1H); LCMS (電灑) m/z 431.2 (M+H)+. | H |
| 259 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.20 (br s, 1H), 8.88 (s, 1H), 8.21 (s, 1H), 8.09 (d, J=1.1 Hz, 1H), 7.66 (br d, J=8.3 Hz, 1H), 7.46 (br d, J=8.8 Hz, 1H), 5.11 - 4.81 (m, 1H), 2.23 - 2.11 (m, 1H), 1.96 (s, 3H), 1.93 (s, 3H), 1.75 - 1.62 (m, 1H), 1.25 - 1.13 (m, 1H); LCMS (電灑) m/z 464.1 (M+H)+. | H |
| 260 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.17 - 13.29 (m, 1H), 11.18 (s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.97 (s, 1H), 7.61 (d, J=9.0 Hz, 1H), 7.36 (dd, J=1.3, 9.2 Hz, 1H), 5.12 - 4.77 (m, 1H), 2.26 (d, J=2.9 Hz, 3H), 2.16 (td, J=7.0, 14.0 Hz, 1H), 1.76 - 1.58 (m, 1H), 1.25 - 1.10 (m, 1H); LCMS (電灑) m/z 402.0 (M+H)+. | H |
| 261 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.29 (s, 1H), 8.89 (s, 1H), 8.20 (s, 1H), 8.17 (s, 1H), 7.67 (d, J=9.0 Hz, 1H), 7.50 (br d, J=9.4 Hz, 1H), 5.09 - 4.82 (m, 1H), 2.18 (td, J=6.9, 13.9 Hz, 1H), 1.75 - 1.62 (m, 1H), 1.26 - 1.14 (m, 1H); LCMS (電灑) m/z 466.1 (M+H)+. | H |
| 262 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.19 (s, 1H), 8.73 (s, 1H), 8.15 (s, 1H), 7.95 (br s, 1H), 7.61 (d, J=9.3 Hz, 1H), 7.35 (d, J=7.8 Hz, 1H), 5.17 - 4.75 (m, 1H), 2.25 (d, J=2.9 Hz, 3H), 2.28 - 2.12 (m, 1H),1.72 - 1.59 (m, 1H), 1.24 - 1.10 (m, 1H); LCMS (電灑) m/z 386.3 (M+H)+. | H |
| 263 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.78 (s, 1H), 7.93 (s, 1H), 7.85 (d, J = 9.2 Hz, 1H), 7.71 (d, J = 9.5 Hz, 1H), 5.06 - 4.94 (m, 1H), 2.31 (d, J = 3.1 Hz, 3H), 2.16 - 2.09 (m, 1H), 1.93 - 1.79 (m, 1H), 1.33 - 1.22 (m, 1H); LCMS (電灑) m/z 436.0 (M+H)+. | H |
| 264 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38 (br s, 1H), 11.28 (br s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.85 (s, 1H), 7.64 (d, J=9.0 Hz, 1H), 7.52 (s, 1H), 7.44 (br d, J=9.0 Hz, 1H), 7.14 (dd, J=11.4, 17.7 Hz, 1H), 6.12 (br d, J=17.9 Hz, 1H), 5.51 (d, J=11.5 Hz, 1H), 5.07 - 4.86 (m, 1H), 2.34 (s, 3H), 2.16 (td, J=7.0, 13.8 Hz, 1H), 1.76 - 1.60 (m, 1H), 1.20 (tdd, J=6.4, 9.1, 12.3 Hz, 1H); LCMS (電灑) m/z 376.1 (M+H)+. | H |
| 265 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.09 (br s, 1H), 11.12 (s, 1H), 8.72 (s, 1H), 8.15 (s, 1H), 7.90 (br s, 1H), 7.56 (d, J=9.2 Hz, 1H), 7.35 (br d, J=9.2 Hz, 1H), 5.11 - 4.75 (m, 1H), 3.17 (br d, J=2.1 Hz, 3H), 2.16 (td, J=6.9, 13.8 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS (電灑) m/z 417.1 (M+H)+. | H |
| 266 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.79 (br s, 1H), 11.14 (s, 1H), 8.84 (s, 1H), 8.19 (s, 1H), 8.06 (s, 1H), 7.61 (d, J=9.3 Hz, 1H), 7.41 (dd, J=1.6, 9.3 Hz, 1H), 5.08 - 4.80 (m, 1H), 2.58 (s, 3H), 2.22 - 2.11 (m, 1H), 1.74 - 1.60 (m, 1H), 1.18 (tdd, J=6.2, 9.1, 12.4 Hz, 1H); LCMS (電灑) m/z 434.2 (M+H)+. | H |
| 267 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.52 (br s, 1H), 11.19 (s, 1H), 8.90 (s, 1H), 8.22 (d, J=3.4 Hz, 2H), 7.65 (d, J=9.3 Hz, 1H), 7.44 (dd, J=1.7, 9.3 Hz, 1H), 5.07 - 4.80 (m, 1H), 3.56 (s, 3H), 2.21 - 2.14 (m, 1H), 1.72 - 1.62 (m, 1H), 1.24 - 1.15 (m, 1H); LCMS (電灑) m/z 466.1 (M+H)+. | H |
| 268 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.29 (s, 1H), 8.78 (s, 1H), 8.17 (s, 1H), 7.99 (s, 1H), 7.65 (d, J=9.1 Hz, 1H), 7.42 (dd, J=1.6, 9.1 Hz, 1H), 5.08 - 4.84 (m, 1H), 2.26 (d, J=3.0 Hz, 3H), 2.21 - 2.11 (m, 1H), 1.75 - 1.62 (m, 1H), 1.20 (tdd, J=6.3, 9.0, 12.4 Hz, 1H); LCMS (電灑) m/z 446.2 (M+H)+. | H |
| 269 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.22 (s, 1H), 8.76 (s, 1H), 8.16 (s, 1H), 7.89 (s, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.41 (dd, J = 1.6, 9.1 Hz, 1H), 5.06 - 5.02 (m, 1H), 4.90 - 4.84 (m, 1H), 2.52 (s, 3H), 2.23 (d, J = 2.9 Hz, 3H), 2.20 - 2.12 (m, 1H), 1.75 - 1.63 (m, 1H), 1.26 - 1.14 (m, 1H); LCMS (電灑) m/z 414.1 (M+H)+. | H |
| 270 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.23 (br s, 1H), 11.20 (s, 1H), 8.79 (s, 1H), 8.19 (s, 1H), 8.03 (s, 1H), 7.64 (d, J = 9.2 Hz, 1H), 7.37 (dd, J = 1.7, 9.1 Hz, 1H), 5.06 - 4.84 (m, 1H), 3.50 (br s, 3H), 2.27 (d, J = 2.8 Hz, 3H), 2.21 - 2.12 (m, 1H), 1.73 - 1.62 (m, 1H), 1.23 - 1.14 (m, 1H); LCMS (電灑) m/z 446.2 (M+H)+. | H |
| 271 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54 (br s, 1H), 11.27 (s, 1H), 8.73 (s, 1H), 8.16 (s, 1H), 7.84 (s, 1H), 7.64 (d, J=9.3 Hz, 1H), 7.41 (dd, J=1.4, 9.1 Hz, 1H), 5.13 - 4.79 (m, 1H), 4.08 (d, J=1.0 Hz, 3H), 2.22 (d, J=3.1 Hz, 3H), 2.20 - 2.10 (m, 1H), 1.77 - 1.60 (m, 1H), 1.20 (tdd, J=6.3, 9.1, 12.4 Hz, 1H); LCMS (電灑) m/z 398.2 (M+H)+. | H |
| 272 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.81 (br s, 1H), 11.15 (s, 1H), 8.80 (s, 1H), 8.17 (s, 1H), 8.00 (s, 1H), 7.61 (d, J=9.3 Hz, 1H), 7.39 (dd, J=1.6, 9.2 Hz, 1H), 5.12 - 4.81 (m, 1H), 4.16 (d, J=1.5 Hz, 3H), 2.22 - 2.11 (m, 1H), 1.75 - 1.60 (m, 1H), 1.18 (tdd, J=6.3, 9.1, 12.4 Hz, 1H); LCMS (電灑) m/z 418.2 (M+H)+. | H |
| 273 |  | 1H NMR (400 MHz, DMSO-d 6) δ 10.90 (br s, 1H), 8.63 (s, 1H), 8.13 (s, 1H), 7.73 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 5.03 - 4.80 (m, 1H), 3.00 (s, 6H), 2.19 (d, J = 2.9 Hz, 3H), 2.18 - 2.14 (m, 1H), 1.78 - 1.65 (m, 1H), 1.24 - 1.14 (m, 1H); LCMS (電灑) m/z 411.2 (M+H)+. | H |
| 274 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.29 (s, 1H), 10.19 (s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.82 (s, 1H), 7.66 (s, 1H), 7.64 (s, 1H), 7.45 (br d, J = 9.9 Hz, 1H), 6.61 - 6.51 (m, 1H), 6.35 (dd, J = 1.8, 16.9 Hz, 1H), 5.89 - 5.84 (m, 1H), 5.08 - 5.03 (m, 1H), 4.89 (dt, J = 3.8, 6.3 Hz, 1H), 2.32 (s, 3H), 2.21 - 2.12 (m, 1H), 1.76 - 1.60 (m, 1H), 1.27 - 1.14 (m, 1H); LCMS (電灑) m/z 419.3 (M+H)+. | H |
| 275 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.80 (br s, 1H), 11.18 (s, 1H), 8.82 (s, 1H), 8.17 (s, 1H), 8.00 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.42 (dd, J=1.5, 9.3 Hz, 1H), 5.11 - 4.81 (m, 1H), 4.40 (q, J=7.1 Hz, 2H), 2.21 - 2.10 (m, 1H), 1.74 - 1.61 (m, 1H), 1.41 (t, J=7.0 Hz, 3H), 1.25 - 1.09 (m, 1H); LCMS (電灑) m/z 432.3 (M+H)+. | H |
| 276 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.23 - 11.08 (m, 1H), 10.40 - 10.29 (m, 1H), 8.80 (s, 1H), 8.17 (s, 1H), 8.01 (br d, J = 7.9 Hz, 2H), 7.59 (br d, J = 9.0 Hz, 1H), 7.46 - 7.36 (m, 1H), 6.66 - 6.49 (m, 1H), 6.41 - 6.36 (m, 1H), 5.95 - 5.85 (m, 1H), 5.12 - 4.78 (m, 1H), 2.22 - 2.08 (m, 1H), 1.77 - 1.58 (m, 1H), 1.27 - 1.10 (m, 1H); LCMS (電灑) m/z 439.2 (M+H)+. | H |
| 277 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.14 (s, 1H), 9.88 (br d, J = 6.7 Hz, 1H), 8.77 (dd, J = 1.0, 1.6 Hz, 1H), 8.19 (s, 1H), 8.03 (br s, 1H), 7.60 (d, J = 9.2 Hz, 1H), 7.36 (dd, J = 1.8, 9.2 Hz, 1H), 5.05 - 5.00 (m, 1H), 4.86 (dt, J = 3.9, 6.2 Hz, 1H), 3.58 (br d, J = 11.0 Hz, 4H), 3.53 - 3.44 (m, 2H), 3.39 - 3.26 (m, 2H), 2.93 (br d, J = 2.7 Hz, 3H), 2.20 - 2.12 (m, 1H), 1.73 - 1.61 (m, 1H), 1.24 - 1.13 (m, 1H); LCMS (電灑) m/z 486.2 (M+H)+. | H |
| 278 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.09 (br s, 1H), 10.92 (s, 1H), 8.64 (s, 1H), 8.13 (s, 1H), 7.75 (s, 1H), 7.52 (d, J=9.2 Hz, 1H), 7.48 (d, J=8.3 Hz, 1H), 7.32 (d, J=8.6 Hz, 1H), 7.26 (dd, J=1.7, 9.2 Hz, 1H), 4.46 (t, J=5.2 Hz, 1H), 3.69 - 3.60 (m, 1H), 3.55 - 3.48 (m, 1H), 2.32 (s, 3H), 2.08 - 1.99 (m, 1H), 1.49 - 1.39 (m, 1H), 1.02 - 0.96 (m, 1H), 0.95 - 0.90 (m, 1H); LCMS (電灑) m/z 362.3 (M+H)+. | H |
| 279 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54 (br s, 1H), 11.21 (s, 1H), 8.81 (s, 1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.62 (d, J = 9.3 Hz, 1H), 7.43 (dd, J = 1.6, 9.2 Hz, 1H), 5.07 - 4.84 (m, 1H), 3.84 - 3.82 (m, 4H), 3.29 (br s, 4H), 2.21 - 2.12 (m, 1H), 1.74 - 1.61 (m, 1H), 1.19 (tdd, J = 6.4, 9.1, 12.4 Hz, 1H); LCMS (電灑) m/z 473.2 (M+H)+. | H |
| 280 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.23 (1 H, s) 8.78 (1 H, s) 8.16 (1 H, s) 7.93 (1 H, br s) 7.61 (1 H, d, J=9.20 Hz) 7.44 (1 H, br d, J=9.40 Hz) 5.16 – 4.71 (1 H, m) 2.17 (1 H, dt, J=14.07, 6.97 Hz) 1.76 - 1.61 (1 H, m) 1.27 - 1.17 (4 H, m); LCMS (電灑) m/z 431.0 (M+H)+. | H |
| 281 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.50 (1 H, br s) 11.38 - 11.10 (1 H, m) 8.99 - 8.77 (1 H, m) 8.17 (1 H, s) 7.96 (1 H, s) 7.77 - 7.57 (1 H, m) 7.53 - 7.35 (1 H, m) 5.14 – 4.79 (1 H, m) 3.39 - 3.37 (1 H, m) 3.30 (4 H, q, J=7.01 Hz) 2.17 (1 H, dt, J=13.88, 7.00 Hz) 1.79 - 1.59 (1 H, m) 1.27 - 1.12 (1 H, m) 1.06 – 0.95 (6 H, m); LCMS (電灑) m/z 459.0 (M+H)+. | H |
| 282 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (br s, 1H), 11.16 (s, 1H), 8.74 (s, 1H), 8.16 (s, 1H), 7.93 (br s, 1H), 7.58 (d, J = 9.0 Hz, 1H), 7.37 (dd, J = 1.5, 9.2 Hz, 1H), 5.07 - 4.82 (m, 1H), 3.72 (br s, 4H), 2.21 - 2.12 (m, 1H), 1.98 - 1.93 (m, 4H), 1.73 - 1.62 (m, 1H), 1.24 - 1.13 (m, 1H); LCMS (電灑) m/z 457.3 (M+H)+. | H |
| 283 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.08 (br s, 1H), 11.08 (s, 1H), 8.70 (s, 1H), 8.14 (s, 1H), 7.89 (br s, 1H), 7.54 (d, J=9.3 Hz, 1H), 7.30 (dd, J=1.6, 9.3 Hz, 1H), 5.06 - 4.79 (m, 1H), 4.39 (br t, J=5.7 Hz, 4H), 2.39 - 2.32 (m, 2H), 2.15 (td, J=7.0, 13.7 Hz, 1H), 1.72 - 1.61 (m, 1H), 1.22 - 1.13 (m, 1H); LCMS (電灑) m/z 443.4 (M+H)+. | H |
| 284 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.22 - 11.10 (m, 1H), 8.76 (br s, 1H), 8.17 (s, 1H), 7.62 - 7.56 (m, 2H), 7.43 - 7.32 (m, 1H), 6.87 (s, 1H), 5.07 - 4.83 (m, 1H), 2.21 - 2.10 (m, 1H), 1.75 - 1.60 (m, 1H), 1.25 - 1.13 (m, 1H); LCMS(電灑) m/z 385.4 (M+H+). | H |
| 285 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36 (br s, 1H), 11.28 (s, 1H), 8.69 (s, 1H), 8.15 (s, 1H), 7.73 (s, 1H), 7.63 (d, J = 9.1 Hz, 1H), 7.43 (br d, J = 9.1 Hz, 1H), 6.83 (s, 1H), 5.08 - 4.86 (m, 1H), 3.99 (s, 3H), 2.32 (s, 3H), 2.21 - 2.12 (m, 1H), 1.75 - 1.63 (m, 1H), 1.27 - 1.12 (m, 1H); LCMS(電灑) m/z 380.5 (M+H+). | H |
| 286 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.53 - 13.11 (m, 1H), 11.23 - 11.11 (m, 1H), 9.82 (s, 1H), 8.80 (br s, 1H), 8.17 (d, J = 11.5 Hz, 2H), 7.89 (s, 1H), 7.65 - 7.57 (m, 1H), 7.43 - 7.32 (m, 1H), 6.72 (dd, J = 10.3, 17.1 Hz, 1H), 6.32 (dd, J = 1.9, 17.0 Hz, 1H), 5.85 - 5.80 (m, 1H), 5.07 - 4.83 (m, 1H), 2.20 - 2.12 (m, 1H), 1.73 - 1.61 (m, 1H), 1.23 - 1.14 (m, 1H); LCMS (電灑) m/z 439.3 (M+H+). | H |
| 287 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.30 (br s, 1H), 11.29 (s, 1H), 8.69 (s, 1H), 8.15 (s, 1H), 7.73 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.43 (br d, J = 8.4 Hz, 1H), 6.82 (s, 1H), 5.07 - 4.86 (m, 1H), 4.28 (q, J = 6.9 Hz, 3H), 2.31 (s, 3H), 2.20 - 2.12 (m, 1H), 1.75 - 1.63 (m, 1H), 1.46 (t, J = 7.0 Hz, 3H), 1.21 (tdd, J = 6.3, 9.0, 12.5 Hz, 1H); LCMS(電灑) m/z 394.1 (M+H+). | H |
| 288 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.48 (br s, 1H), 11.21 (s, 1H), 8.71 (s, 1H), 8.15 (s, 1H), 7.83 (s, 1H), 7.61 (d, J=9.2 Hz, 1H), 7.38 (dd, J=1.3, 9.2 Hz, 1H), 5.12 - 4.79 (m, 1H), 4.31 (q, J=7.0 Hz, 2H), 2.22 (d, J=3.1 Hz, 3H), 2.20 - 2.11 (m, 1H), 1.74 - 1.60 (m, 1H), 1.39 (t, J=7.0 Hz, 3H), 1.19 (tdd, J=6.4, 9.1, 12.4 Hz, 1H); LCMS(電灑) m/z 412.1 (M +H+). | H |
| 289 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.72 (s, 1H), 7.88 - 7.81 (m, 2H), 7.79 (s, 1H), 7.73 (br d, J = 8.8 Hz, 1H), 6.64 - 6.55 (m, 1H), 6.49 - 6.41 (m, 1H), 5.87 (br d, J = 11.6 Hz, 1H), 5.07 - 4.97 (m, 2H), 2.26 (s, 3H), 2.19 - 2.09 (m, 1H), 1.94 - 1.81 (m, 1H), 1.35 - 1.23 (m, 1H); LCMS(電灑) m/z 419.2 (M +H+). | H |
| 290 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.80 (br s, 1H), 11.19 (s, 1H), 8.87 (s, 1H), 8.18 (s, 1H), 8.07 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.46 (dd, J = 1.7, 9.2 Hz, 1H), 5.06 - 4.83 (m, 1H), 3.51 - 3.50 (m, 2H), 3.08 (t, J = 6.7 Hz, 2H), 2.22 - 2.12 (m, 1H), 1.74 - 1.61 (m, 1H), 1.19 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS(電灑) m/z 464 (M+H+). | H |
| 291 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.54 - 11.33 (m, 1H), 8.73 (br d, J=3.3 Hz, 1H), 8.18 (d, J=1.6 Hz, 1H), 7.78 - 7.61 (m, 2H), 7.47 (br t, J=9.4 Hz, 1H), 5.12 - 4.85 (m, 1H), 2.98 (s, 3H), 2.97 (s, 3H), 2.56 (br d, J=7.3 Hz, 2H), 2.17 (td, J=6.9, 13.7 Hz, 1H), 1.78 - 1.59 (m, 1H), 1.29 - 1.21 (m, 1H), 1.10 (t, J=7.4 Hz, 3H); LCMS(電灑) m/z 425.2 (M +H+). | H |
| 292 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.45 (br s, 1H), 11.22 (s, 1H), 8.77 (s, 1H), 8.16 (s, 1H), 7.90 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.41 (dd, J = 1.5, 9.2 Hz, 1H), 5.06 - 4.85 (m, 1H), 3.50 (t, J = 6.9 Hz, 2H), 3.02 (t, J = 6.9 Hz, 2H), 2.23 (d, J = 2.9 Hz, 3H), 2.19 - 2.13 (m, 1H), 1.74 - 1.60 (m, 1H), 1.19 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS(電灑) m/z 444 (M+H+). | H |
| 293 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.89 - 13.08 (m, 1H), 11.22 (br s, 1H), 8.72 (s, 1H), 8.17 (s, 1H), 7.81 (s, 1H), 7.63 (br d, J = 9.1 Hz, 1H), 7.35 (br d, J = 9.1 Hz, 1H), 5.07 - 4.83 (m, 1H), 2.62 - 2.58 (m, 2H), 2.53 (s, 3H), 2.16 (td, J = 6.9, 13.9 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.24 - 1.15 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(電灑) m/z 428.3 (M+H+). | H |
| 294 |  | 1H NMR (400MHz, CHLOROFORM-d) δ 11.24 (s, 1H), 8.73 (s, 1H), 8.18 (s, 1H), 7.75 (s, 1H), 7.64 (d, J = 9.0 Hz, 1H), 7.42 (d, J = 10.4 Hz, 1H), 7.36 (br d, J = 9.0 Hz, 1H), 5.12 - 4.76 (m, 1H), 2.61 (br d, J = 7.3 Hz, 2H), 2.23 - 2.12 (m, 1H), 1.77 - 1.62 (m, 1H), 1.22 - 1.16 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(電灑) m/z 382.3 (M +H+). | H |
| 295 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.51 (d, J = 7.2 Hz, 1H), 7.85 (s, 1H), 7.66 (s, 1H), 7.00 - 6.91 (m, 2H), 5.03 - 4.96 (m, 1H), 2.16 - 2.07 (m, 1H), 1.89 - 1.78 (m, 1H), 1.30 - 1.17 (m, 1H); LCMS(電灑) m/z 404.1 (M+H+). | H |
| 296 |  | 1H NMR (400MHz, CHLOROFORM-d) δ 11.23 (s, 1H), 8.77 (s, 1H), 8.17 (s, 1H), 7.90 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.54 (d, J = 9.3 Hz, 1H), 7.45 (br d, J = 9.3 Hz, 1H), 5.12 - 4.81 (m, 1H), 2.25 (s, 3H), 2.21 - 2.11 (m, 1H), 1.75 - 1.61 (m, 1H), 1.25 - 1.21 (m, 1H); LCMS(電灑) m/z 400.2 (M +H+). | H |
| 297 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.17 (s, 1H), 8.75 (d, J = 0.7 Hz, 1H), 8.17 (s, 1H), 7.97 (s, 1H), 7.59 (br d, J = 9.2 Hz, 1H), 7.44 - 7.39 (m, 1H), 5.16 - 4.80 (m, 1H), 2.56 - 2.54 (m, 3H), 2.38 - 2.30 (m, 1H), 2.27 (s, 3H), 2.21 - 2.11 (m, 1H), 1.77 - 1.62 (m, 1H), 1.25 - 1.12 (m, 1H); LCMS(電灑) m/z 446.0 (M +H+). | H |
| 298 |  | 1H NMR (400 MHz, CHLOROFORM-d) δ 13.00 (s, 1 H), 8.34 - 8.22 (m, 2 H), 7.92 (d, J=9.17 Hz, 1 H), 7.71 - 7.61 (m, 2 H), 5.01 - 4.74 (m, 1 H), 2.67 (br d, J=7.34 Hz, 2 H), 2.20 - 2.15 (m, 1 H), 2.06 - 1.96 (m, 2 H), 1.33 - 1.23 (m, 1 H), 1.17 (t, J=7.46 Hz, 3 H); LCMS(電灑) m/z 400.0 (M +H+). | H |
| 299 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (s, 1H), 8.74 (s, 1H), 8.18 (s, 1H), 7.97 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.36 (br d, J = 8.9 Hz, 1H), 5.09 - 4.78 (m, 1H), 3.13 (s, 3H), 2.23 (d, J = 2.8 Hz, 3H), 2.20 - 2.11 (m, 1H), 1.73 - 1.62 (m, 1H), 1.24 - 1.12 (m, 1H); LCMS(電灑) m/z 429.11 (M +H+). | H |
| 300 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (br s, 1H), 11.22 (s, 1H), 8.71 (s, 1H), 8.16 (s, 1H), 7.86 (s, 1H), 7.60 (d, J = 9.2 Hz, 1H), 7.43 (br d, J = 9.0 Hz, 1H), 5.08 - 4.85 (m, 1H), 2.99 (d, J = 2.3 Hz, 6H), 2.27 (s, 3H), 2.21 - 2.12 (m, 1H), 1.76 - 1.61 (m, 1H), 1.26 - 1.16 (m, 1H); LCMS(電灑) m/z 443 (M+H+). | H |
| 301 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.20 (s, 1H), 10.15 (s, 1H), 8.87 (s, 1H), 8.19 (s, 1H), 7.98 (s, 1H), 7.64 (d, J = 9.3 Hz, 1H), 7.46 (dd, J = 1.5, 9.2 Hz, 1H), 5.08 - 4.82 (m, 1H), 2.18 (s, 3H), 2.17 - 2.11 (m, 1H), 1.74 - 1.62 (m, 1H), 1.26 - 1.15 (m, 1H); LCMS(電灑) m/z 445.2 (M +H+). | H |
| 302 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38 - 13.09 (m, 1H), 11.19 (s, 1H), 8.80 (s, 1H), 8.19 (s, 1H), 8.03 (s, 1H), 7.64 (d, J = 9.1 Hz, 1H), 7.38 (dd, J = 1.6, 9.2 Hz, 1H), 5.09 - 4.78 (m, 1H), 3.50 (s, 3H), 2.27 (d, J = 2.8 Hz, 3H), 2.21 - 2.12 (m, 1H), 1.74 - 1.61 (m, 1H), 1.19 (tdd, J = 6.3, 9.0, 12.4 Hz, 1H); LCMS(電灑) m/z 446.0 (M +H+). | H |
| 303 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.15 (s, 1H), 8.87 (d, J = 0.6 Hz, 1H), 8.20 (s, 1H), 8.15 (s, 1H), 7.63 (d, J = 9.3 Hz, 1H), 7.42 (dd, J = 1.7, 9.3 Hz, 1H), 5.07 - 4.82 (m, 1H), 3.19 (s, 3H), 2.21 - 2.11 (m, 1H), 1.74 - 1.61 (m, 1H), 1.24 - 1.12 (m, 1H); LCMS(電灑) m/z 450 (M+H+). | H |
| 304 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.28 (br s, 1H), 8.77 (s, 1H), 8.17 (s, 1H), 8.05 (br d, J = 2.0 Hz, 1H), 7.63 (br d, J = 9.1 Hz, 1H), 7.45 (br d, J = 9.1 Hz, 1H), 5.06 - 5.02 (m, 1H), 4.89 - 4.87 (m, 1H), 2.30 (s, 3H), 2.21 - 2.12 (m, 1H), 1.75 - 1.61 (m, 1H), 1.24 - 1.13 (m, 1H); LCMS(電灑) m/z 418 (M +H+). | H |
| 305 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.80 (s, 1H), 7.89 - 7.86 (m, 2H), 7.77 (d, J = 8.9 Hz, 1H), 5.05 - 4.96 (m, 1H), 4.06 (s, 3H), 2.30 (d, J = 3.1 Hz, 3H), 2.13 (ddd,J = 2.3, 4.5, 6.6 Hz, 1H), 1.91 - 1.81 (m, 1H), 1.31 - 1.25 (m, 1H); LCMS(電灑) m/z 426.2 (M+H+). | H |
| 306 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.27 (s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.65 (d, J = 9.2 Hz, 1H), 7.49 (dd, J = 1.6, 9.2 Hz, 1H), 5.04 (dt, J = 3.8, 6.2 Hz, 1H), 4.89 - 4.85 (m, 1H), 3.27 (q, J = 6.9 Hz, 2H), 2.98 (d, J = 2.6 Hz, 3H), 2.20 - 2.12 (m, 1H), 1.73 - 1.63 (m, 1H), 1.20 (tdd, J = 6.3, 9.0, 12.4 Hz, 1H), 1.08 (t, J = 7.1 Hz, 3H); LCMS(電灑) m/z 445.2 (M +H+). | H |
| 307 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.14 (s, 1H), 8.68 (s, 1H), 8.13 (s, 1H), 7.86 (br d, J = 3.4 Hz, 1H), 7.55 (d, J = 9.2 Hz, 1H), 7.24 (d, J = 9.2 Hz,1H), 5.06 - 4.79 (m, 1H), 3.02 (d, J = 2.0 Hz, 6H), 2.21 - 2.11 (m, 1H), 1.73 - 1.61 (m, 1H), 1.21 - 1.11 (m, 1H); LCMS(電灑) m/z 465.1 (M+H+). | H |
| 308 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.14 - 12.81 (m, 1H), 11.30 - 11.11 (m, 1H), 9.94 (s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.80 (s, 1H), 7.66 - 7.59 (m, 1H), 7.43 - 7.32 (m, 1H), 5.07 - 4.81 (m, 1H), 2.22 (d, J = 2.9 Hz, 3H), 2.16 (s, 4H), 1.74 - 1.62 (m, 1H), 1.27 - 1.12 (m, 1H); LCMS(電灑) m/z 424.15 (M +H+). | H |
| 309 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.29 (s, 1H), 11.07 (s, 1H), 8.74 (s, 1H), 8.41 (s, 1H), 7.93 (s, 1H), 7.54 (d, J = 9.2 Hz, 1H), 7.29 (d, J = 9.2 Hz, 1H), 5.01 - 4.83 (m, 1H), 3.22 (s, 3H), 2.23 - 2.16 (m, 1H), 1.78 - 1.61 (m, 1H), 1.23 (br, 9H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 532.1 (M+H)+. | H |
| 310 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.02 - 13.34 (m, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.85 (s, 1H), 7.65 (s, 1H), 6.93 (s, 1H), 6.89 (dd, J = 1.8, 7.1 Hz, 1H), 5.11 - 4.78 (m, 1H), 4.35 (q, J = 7.0 Hz, 2H), 2.28 (s, 3H), 2.19 - 2.12 (m, 1H), 1.68 (m, J = 3.2, 6.8, 19.9 Hz, 1H), 1.41 (t, J = 7.0 Hz, 3H), 1.26 - 1.11 (m, 1H); LCMS(電灑) m/z 444.2 (M+H+). | H |
| 311 |  | 1H NMR (400 MHz, DMSO-d 6) δ 10.85 (br s, 1H), 8.70 (s, 1H), 8.15 (s, 1H), 7.89 (s, 1H), 7.60 (d, J = 9.0 Hz, 1H), 7.36 (dd, J = 1.5, 9.1 Hz, 1H), 5.05 - 4.79 (m, 2H), 2.27 (br d, J = 2.6 Hz, 3H), 1.80 (s, 3H), 1.77 - 1.63 (m, 1H), 1.18 (tdd, J = 6.3, 9.2, 12.2 Hz, 1H); LCMS(電灑) m/z 438.16 (M +H+). | H |
| 312 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.78 (s, 1H), 7.91 - 7.83 (m, 3H), 7.80 - 7.75 (m, 1H), 5.01 (dt, J = 3.9, 6.2 Hz, 1H), 4.13 (br t, J = 6.5 Hz, 2H), 3.17 (br t, J = 6.7 Hz, 2H), 2.63 (s, 3H), 2.29 (d, J = 2.9 Hz, 3H), 2.17 - 2.09 (m, 1H), 1.92 - 1.81 (m, 1H), 1.31 - 1.26 (m, 1H); LCMS(電灑) m/z501.3 (M +H+). | H |
| 313 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.19(br s, 1H), 11.16 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.91 (s, 1H), 7.61 (d, J = 9.0 Hz, 1H), 7.36 (br d, J = 8.9 Hz, 1H), 5.04 - 4.85(m, 1H), 2.23 (d, J = 3.1 Hz, 3H), 2.19 - 2.16 (m, 1H), 1.72 - 1.63 (m, 1H), 1.18 (ddd, J = 2.6, 6.2, 9.2 Hz, 1H); LCMS(電灑) m/z 412.1 (M+H+). | H |
| 314 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (br s, 1H), 11.13 (s, 1H), 8.88 (s, 1H), 8.19 (s, 1H), 8.08 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.41 (dd, J = 1.8, 9.2 Hz, 1H), 5.06 - 4.83 (m, 1H), 2.22 - 2.12 (m, 1H), 1.74 - 1.57 (m, 1H), 1.29 - 1.06 (m, 1H); LCMS(電灑) m/z 432.2 (M +H+). | H |
| 315 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.69 - 13.54 (m, 1H), 11.16 (s, 1H), 8.90 (s, 1H), 8.20 (s, 1H), 8.13 (s, 1H), 7.63 (br d, J = 9.2 Hz, 1H), 7.44 (br d, J = 9.4 Hz, 1H), 5.12 (d, J = 6.5 Hz, 1H), 4.01 (s, 3H), 2.23 - 2.11 (m, 1H), 1.76 - 1.61 (m, 1H), 1.28 - 1.08 (m, 1H); LCMS(電灑) m/z 446.2 (M +H+). | H |
| 316 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.22 - 13.73 (m, 1H), 11.15 (s, 1H), 8.87 - 8.86 (m, 1H), 8.19 (s, 1H), 8.13 (s, 1H), 7.62 (d, J = 9.3 Hz, 1H), 7.47 - 7.40 (m, 1H), 5.04 - 4.84 (m, 1H), 3.23 (s, 3H), 2.17 (ddd, J = 2.0, 5.0, 6.9 Hz, 1H), 1.82 (s, 3H), 1.71 - 1.63 (m, 1H), 1.19 - 1.13 (m, 1H); LCMS(電灑) m/z 459.1 (M +H+). | H |
| 317 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.93 (s, 1H), 11.06 (s, 1H), 8.70 (s, 1H), 8.14 (s, 1H), 7.79 (s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.38 (s, 1H), 7.31 (d, J = 9.2 Hz, 1H), 5.01 - 4.83 (m, 1H), 5.01 (s, 1H), 2.60 (s, 3H), 2.23 - 2.16 (m, 1H), 1.78 - 1.61 (m, 1H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 432.1 (M+H)+. | H |
| 318 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.60 - 13.32 (m, 1H), 11.06 (s, 1H), 8.63 (s, 1H), 8.15 (s, 1H), 7.74 (s, 1H), 7.54 (d, J = 9.1 Hz, 1H), 7.21 (dd, J = 1.6, 9.1 Hz, 1H), 5.04 - 4.82 (m, 1H), 4.32 (q, J = 7.0 Hz, 2H), 2.60 (br d, J = 6.6 Hz, 2H), 2.20 - 2.11 (m, 1H), 1.72 - 1.61 (m, 1H), 1.39 (t, J = 6.9 Hz, 3H), 1.20 - 1.13 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(電灑) m/z 426.0 (M+H+). | H |
| 319 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.73 (s, 1H), 11.13 (s, 1H), 8.89 (s, 1H), 8.22 (s, 1H), 8.10 (s, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.40 (dd, J = 1.5, 9.2 Hz, 1H), 5.08 - 4.81 (m, 1H), 2.77 (d, J = 6.1 Hz, 3H), 2.25 - 2.12 (m, 1H), 1.76 - 1.61 (m, 1H), 1.13-1.19 (m, J = 2.9, 6.1, 12.1 Hz, 1H); LCMS(電灑) m/z 430.3(M+H+). | H |
| 320 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.10 (s, 1H), 8.89 (s, 1H), 8.19 (s, 1H), 8.06 (s, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 1.7, 9.3 Hz, 1H), 5.10 - 4.79 (m, 1H), 3.13 (s, 3H), 2.93 (s, 3H), 2.21 - 2.12 (m, 1H), 1.75 - 1.60 (m, 1H), 1.08 (s, 1H); LCMS(電灑) m/z 459.0 (M +H+). | H |
| 321 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.19 - 11.05 (m, 1H), 8.90 - 8.81 (m, 1H), 8.69 - 8.61 (m, 1H), 8.49 - 8.44 (m, 1H), 8.26 - 8.16 (m, 1H), 8.07 - 8.00 (m, 1H), 7.68 - 7.54 (m, 1H), 7.42 - 7.31 (m, 1H), 5.15 - 4.75 (m, 1H), 2.91 (d, J = 4.2 Hz, 3H), 2.23 - 2.11 (m, 1H), 1.76 (br d, J = 4.8 Hz, 1H), 1.27 - 1.10 (m, 1H); LCMS(電灑) m/z 445.3 (M +H+). | H |
| 322 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.43 (s, 1H), 11.10 (s, 1H), 8.77 (s, 1H), 8.18 (s, 1H), 7.92 (s, 1H), 7.59 (d, J = 9.2 Hz, 1H), 7.31 (dd, J = 1.6, 9.2 Hz, 1H), 5.08 - 4.79 (m, 1H), 2.74 (d, J = 6.2 Hz, 3H), 2.28 (d, J = 3.2 Hz, 3H), 2.16 (td, J = 6.9, 13.9 Hz, 1H), 1.75 - 1.58 (m, 1H), 1.17 (tdd, J = 6.3, 9.1, 12.2 Hz, 1H); LCMS(電灑) m/z 409.14 (M +H+). | H |
| 323 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.21 - 11.16 (m, 1H), 8.83 (s, 1H), 8.18 (s, 1H), 8.15 (br s, 1H), 7.71 - 7.59 (m, 1H), 7.41 (dd, J = 1.6, 9.2 Hz, 1H), 5.06 - 4.83 (m, 1H), 2.22 - 2.11 (m, 1H), 1.74 - 1.59 (m, 1H), 1.19 (tdd, J = 6.4, 9.1, 12.4 Hz, 1H); LCMS(電灑) m/z 406.1 (M +H+). | H |
| 324 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38 (br s, 1H), 11.06 (s, 1H), 8.66 (s, 1H), 8.13 (s, 1H), 7.84 (br s, 1H), 7.51 (d, J = 9.1 Hz, 1H), 7.30 (br d, J = 8.5 Hz, 1H), 5.06 - 4.81 (m, 1H), 3.25 - 3.20 (m, 2H), 2.95 (br s, 3H), 2.25 (s, 3H), 2.16 - 2.15 (m, 1H), 1.70 - 1.63 (m, 1H), 1.19 - 1.13 (m, 1H), 1.07 (t, J = 7.1 Hz, 3H); LCMS(電灑) m/z 457 (M+H+). | H |
| 325 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.55 (s, 1H), 11.12 (s, 1H), 8.86 (s, 1H), 8.20 (s, 1H), 8.05 (d, J = 16.9 Hz, 3H), 7.61 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 1.6, 9.2 Hz, 1H), 5.11 - 4.79 (m, 1H), 2.24 - 2.08 (m, 1H), 1.78 - 1.57 (m, 1H), 1.21 - 1.14 (m,1H); LCMS(電灑) m/z 431.1 (M+H+). | H |
| 326 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.16 (br s, 1H), 11.06 (s, 1H), 8.63 (s, 1H), 8.14 (s, 1H), 7.68 (s, 1H), 7.53 (d, J=9.2 Hz, 1H), 7.22 (d, J=9.3 Hz, 1H), 5.06 - 4.78 (m, 1H), 3.27 - 3.11 (m, 2H), 2.94 (s, 4H), 2.57 (br d, J=6.8 Hz, 2H), 2.21 - 2.09 (m, 1H), 1.76 - 1.58 (m, 1H), 1.25 - 1.14 (m, 1H), 1.11 - 1.04 (m, 6H); LCMS(電灑) m/z 439.2 (M+H+). | H |
| 327 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.52 (br s, 1H), 11.08 (s, 1H), 8.76 (s, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 7.58 (d, J=9.2 Hz, 1H), 7.37 (d, J=9.3 Hz, 1H), 3.00 (d, J=1.7 Hz, 6H), 2.01 - 1.90 (m, 1H), 0.92 - 0.78 (m, 4H); LCMS(電灑) m/z 413.0 (M+H+). | H |
| 328 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.24 (br s, 1H), 11.07 (s, 1H), 8.84 (s, 1H), 8.19 (s, 1H), 8.02 (s, 1H), 7.58 - 7.54 (m, 1H), 7.50 - 7.44 (m, 2H), 5.04 - 4.81 (m, 1H), 3.85 (q, J = 7.0 Hz, 2H), 2.20 - 2.12 (m, 1H), 1.67 (tdd, J = 3.3, 6.8, 20.0 Hz, 1H), 1.21 - 1.14 (m, 1H), 1.10 (t, J = 7.0 Hz, 3H); LCMS(電灑) m/z 398.1 (M+H+). | H |
| 329 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.41 (br s, 1H), 11.08 (s, 1H), 8.73 (s, 1H), 8.16 (s, 1H), 7.88 (s, 1H), 7.57 (d, J = 9.1 Hz, 1H), 7.31 (dd, J = 1.4, 9.3 Hz, 1H), 5.08 - 4.81 (m, 1H), 3.12 (s, 3H), 2.92 (s, 3H), 2.24 (d, J = 2.8 Hz, 3H), 2.19 - 2.11 (m, 1H), 1.72 - 1.59 (m, 1H), 1.19 - 1.15 (m, 1H); LCMS(電灑) m/z 439.3 (M+H+). | H |
| 330 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (s, 1H), 11.05 (s, 1H), 8.65 (s, 1H), 8.13 (s, 1H), 7.76 (s, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.27 (dd, J = 1.6, 9.2 Hz, 1H), 5.07 - 4.79 (m, 1H), 3.20 (q, J = 6.6 Hz, 2H), 2.92 (s, 3H), 2.21 - 2.12 (m, 4H), 1.73 - 1.59 (m, 1H), 1.25 - 1.10 (m, 1H), 1.05 (t, J = 7.1 Hz, 3H); LCMS(電灑) m/z 424.18 (M +H+). | H |
| 331 |  | 1H NMR (400 MHz, DMSO-d 6) δ 1.12-1.22 (m, 1 H), 1.60-1.73 (m, 1 H), 2.12-2.21 (m, 1 H), 4.81-5.05 (m, 1 H), 7.39 (dd, J=9.26, 1.75 Hz, 1 H), 7.50 (s, 1 H) 7.58-7.64 (m, 1 H), 7.77 (s, 1 H), 8.14 (s, 1 H), 8.19 (s, 1 H), 8.87 (s, 1 H), 11.11 (s, 1 H), 13.86-13.91 (m, 1 H); LCMS(電灑) m/z 438.1 (M+H+). | H |
| 332 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (br s, 1H), 11.19 (s, 1H), 8.74 (s, 1H), 8.11 (s, 1H), 8.00 - 7.84 (m, 1H), 7.56 (d, J=9.3 Hz, 1H), 7.33 (dd, J=1.4, 9.2 Hz, 1H), 5.04 - 4.78 (m, 1H), 3.00 (br s, 6H), 2.46 - 2.41 (m, 1H), 1.61 - 1.44 (m, 1H), 1.25 (qd, J=6.6, 13.1 Hz, 1H); LCMS(電灑) m/z 431.0 (M+H+). | H |
| 333 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.99 - 13.12 (m, 1H), 11.27 (s, 1H), 8.78 (s, 1H), 8.13 (s, 1H), 7.93 (s, 1H), 7.60 (d, J=9.3 Hz, 1H), 7.39 (d, J=9.3 Hz, 1H), 5.05 - 4.75 (m, 1H), 3.00 (d, J=2.4 Hz, 6H), 2.44 (br s, 1H), 1.63 - 1.46 (m, 1H), 1.26 (qd, J=6.4, 13.2 Hz, 1H); LCMS(電灑) m/z 431.1 (M+H+). | H |
| 334 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.77 - 13.25 (m, 1H), 11.15 (s, 1H), 8.78 (s, 1H), 8.17 (s, 1H), 7.94 (s, 1H), 7.59 (d, J=9.2 Hz, 1H), 7.38 (d, J=9.3 Hz, 1H), 5.09 - 4.80 (m, 1H), 3.00 (d, J=2.3 Hz, 6H), 2.16 (td, J=6.8, 13.6 Hz, 1H), 1.73 - 1.58 (m, 1H), 1.24 - 1.10 (m, 1H); LCMS(電灑) m/z 431.1 (M+H+). | H |
| 335 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.34 (br s, 1H), 11.05 (s, 1H), 8.93 (s, 1H), 8.29 (s, 1H), 8.19 (s, 1H), 7.60 - 7.56 (m, 1H), 7.55 - 7.51 (m, 1H), 7.15 (d, J = 13.7 Hz, 1H), 5.06 - 4.80 (m, 1H), 2.95 (d, J = 1.2 Hz, 6H), 2.22 - 2.09 (m, 1H), 1.75 - 1.59 (m, 1H), 1.16 (br s, 1H); LCMS(電灑) m/z 397.2 (M+H+). | H |
| 336 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.68 (s, 1H), 11.09 (s, 1H), 8.83 (s, 1H), 8.18 (s, 1H), 8.08 (s, 1H), 7.59 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 9.0 Hz, J = 1.8 Hz, 1H), 5.03 - 4.83 (m, 1H), 3.84 (t, J = 6.8 Hz, 2H), 2.52 (t, J = 7.4 Hz, 2H), 2.31-2.24 (m, 2H), 2.18-2.13 (m, 1H), 1.71 - 1.63 (m, 1H), 1.23 - 1.12 (m, 1H); LCMS (電灑) m/z 471.1 (M+H)+. | H |
| 337 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.62 (s, 1H), 11.06 (s, 1H), 8.82 (s, 1H), 8.16 (s, 1H), 8.11 (br, 1H), 8.08 (s, 1H), 7.59 - 7.55 (m, 2H), 7.38 (dd, J = 9.0 Hz, J = 1.8 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 6.54 (d, J = 8.0 Hz, 1H), 5.03 - 4.83 (m, 1H), 3.41 (s, 3H), 2.18-2.13 (m, 1H), 1.71 - 1.63 (m, 1H), 1.23 - 1.12 (m, 1H); LCMS (電灑) m/z 494.1 (M+H)+. | H |
| 338 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.22 (s, 1H), 11.07 (s, 1H), 8.79 - 8.65 (m, 1H), 8.46 - 8.34 (m, 1H), 8.17 (s, 1H), 7.90 - 7.78 (m, 1H), 7.65 - 7.51 (m, 1H), 7.36 - 7.22 (m, 1H), 5.08 - 4.78 (m, 1H), 2.89 (br d, J = 4.5 Hz, 3H), 2.24 (br d, J = 2.8 Hz, 3H), 2.19 - 2.13 (m, 1H), 1.74 - 1.58 (m, 1H), 1.23 - 1.11 (m, 1H); LCMS(電灑) m/z 425.1 (M +H+). | H |
| 339 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.67 (br s, 1H), 11.10 (s, 1H), 8.73 (s, 1H), 8.18 (s, 1H), 7.97 (s, 1H), 7.60 (d, J = 9.1 Hz, 1H), 7.27 (dd, J = 1.6, 9.1 Hz, 1H), 5.05 - 4.81 (m, 1H), 2.66 (br d, J = 7.3 Hz, 2H), 2.22 - 2.11 (m, 1H), 1.74 - 1.61 (m, 1H), 1.20 - 1.14 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(電灑) m/z 450.2 (M +H+). | H |
| 340 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.48 (br s, 1 H) 11.05 (s, 1 H) 8.94 (s, 1 H) 8.36 (br s, 1 H) 8.21 (s, 1 H) 7.52 - 7.62 (m, 2 H) 7.37 (br d, J=7.25 Hz, 1 H) 7.29 (d, J=7.50 Hz, 1 H) 4.81 - 5.04 (m, 1 H) 2.62 (s, 3 H) 2.12 - 2.20 (m, 1 H) 1.61 - 1.73 (m, 1 H) 1.12 - 1.23 (m, 1 H); LCMS(電灑) m/z 382.1 (M+H+). | H |
| 341 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 (s, 1 H), 11.06 (s, 1 H), 8.81 (s, 1 H), 8.14(s, 1 H), 8.01 (s, 1 H), 7.54 (s, 1 H), 7.37 - 7.34 (m, 1 H), 4.98 - 4.80 (m, 1 H), 3.23 - 3.17 (q, J = 7.0 Hz, 1H), 2.87 (s, 3 H), 2.14 - 2.10 (m, 1 H), 1.66 - 1.59 (m, 1 H), 1.16 - 1.10 (m, 1 H), 1.00 (t, J= 6.9 Hz, 3 H); LCMS(電灑) m/z 473.1 (M+H+). | H |
| 342 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.63 (s, 1 H) 11.17 (s, 1 H) 9.07 (s, 1 H) 8.43(s, 1 H) 8.21 (s, 1 H) 7.72 - 7.61 (m, 2 H) 7.32 (d, J=10.4 Hz, 1 H) 5.05 - 4.85 (m, 1 H) 2.51 (s, 3 H) 2.20 - 2.15 (m, 1 H) 1.72 - 1.65 (m, 1 H) 1.22 - 1.16 (m, 1 H); LCMS(電灑) m/z 400.0 (M+H+). | H |
| 343 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54 (s, 1H), 11.09 (s, 1H), 8.75 (s, 1H), 8.16 (s, 1H), 7.94 (d, J = 1.0 Hz, 1H), 7.73 - 7.43(m, 2H), 7.30 (dd, J = 1.6, 9.2 Hz, 1H), 5.10 - 4.79 (m, 1H), 2.24 (d, J = 2.6 Hz, 3H), 2.19 - 2.12 (m, 1H), 1.74 - 1.61 (m, 1H),1.17 (ddd, J = 2.9, 6.2, 12.2 Hz, 1H); LCMS(電灑) m/z 418.1 (M+H+). | H |
| 344 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.08 (br s, 1H), 11.11 (s, 1H), 9.05 (s, 1H), 8.49 (s, 1H), 8.21 (s, 1H), 7.68 - 7.63 (m, 1H), 7.61 - 7.57 (m, 1H), 7.48 (d, J = 11.6 Hz, 1H), 5.12 - 4.84 (m, 1H), 2.25 - 2.12 (m, 1H), 1.83 - 1.60 (m, 1H), 1.27 - 1.08 (m, 1H); LCMS(電灑) m/z 438.2 (M+H+). | H |
| 345 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.94 (s, 1H), 11.09 (s, 1H), 8.74 (s, 1H), 8.15 (s, 1H), 7.99 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.31 (dd, J = 1.7, 9.2 Hz, 1H), 5.08 - 4.77 (m, 1H), 2.26 (d, J = 2.8 Hz, 3H), 2.20 - 2.11 (m, 1H), 1.73 - 1.59 (m, 1H), 1.23 -1.10 (m, 1H); LCMS(電灑) m/z 452.3 (M+H+). | H |
| 346 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.61 (s, 1H), 11.10 (s, 1H), 8.86 (s, 1H), 8.63-8.47 (br, 2H), 8.20 (s, 1H), 8.03 (s, 1H), 7.60 (d, J = 9.6 Hz, 1H), 7.43 (t, J = 4.6 Hz, 1H), 6.86 (t, J = 6.0 Hz, 1H), 5.04 - 4.83 (m, 1H), 3.53 (s, 3H), 2.20-2.13 (m, 1H), 1.72 - 1.62 (m, 1H), 1.23 - 1.13 (m, 1H); LCMS (電灑) m/z 495.1 (M+H)+. | H |
| 347 |  | 1H NMR (400 MHz, ACETONE-d 6) δ 13.30 (s, 1H), 10.52 (s, 1H), 9.23 (s, 1H), 8.72 (s, 1H), 8.61 (s, 1H), 8.04 (d, J = 9.3 Hz, 1H), 7.90 (d, J = 9.1 Hz, 1H), 5.47 - 5.26 (m, 1H), 4.96 - 4.73 (m, 2H), 3.75 (s, 3H), 2.76 - 2.71 (m, 1H), 2.33 - 2.24 (m, 1H), 1.70 - 1.63 (m, 1H); LCMS(電灑) m/z 527.1 (M+H+). | H |
| 348 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.61 (s, 1H), 11.10 (s, 1H), 8.86 (s, 1H), 8.63 (br, 1H), 8.47 (br, 1H), 8.20 (s, 1H), 8.08 (s, 1H), 7.60 (d, J = 9.6 Hz, 1H), 7.55 (br, 1H), 7.42 (t, J = 8.0 Hz, 1H), 5.04 - 4.83 (m, 1H), 3.48 (s, 3H), 2.20-2.15 (m, 1H), 1.72 - 1.62 (m, 1H), 1.23 - 1.13 (m, 1H); LCMS (電灑) m/z 495.1 (M+H)+. | H |
| 349 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.66 (s, 1H), 11.09 (s, 1H), 8.77 (s, 1H), 8.59 (s, 1H), 8.46 (s, 1H), 8.20 (s, 1H), 7.96 (s, 1H), 7.82 (d, J = 6.8 Hz, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.34 (t, J = 8.2 Hz, 2H), 5.04 - 4.83 (m, 1H), 4.45 (s, 2H), 2.90 (s, 3H), 2.20-2.15 (m, 1H), 1.72 - 1.62 (m, 1H), 1.23 - 1.13 (m, 1H); LCMS (電灑) m/z 508.1 (M+H)+. | H |
| 350 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.18-13.20 (m, 1H), 11.22 (s, 1H), 8.74 (d, J = 7.2 Hz, 1H), 8.15 (s, 1H), 7.89 (s, 1H), 7.10-6.94 (m, 2H), 5.16-4.74 (m, 1H), 4.12 (s, 3H), 2.25-2.09 (m, 1H), 1.78-1.54 (m, 1H), 1.29-1.05 (m, 1H); LCMS(電灑) m/z 470.2 (M+H+). | H |
| 351 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.75 - 14.36 (m, 1H), 11.13 (s, 1H), 8.90 (s,1H), 8.27 (s, 1H), 8.21 (s, 1H), 7.62 (d, J = 9.2Hz, 1H), 7.41 (dd, J = 1.5, 9.3 Hz, 1H), 5.09 - 4.80 (m, 1H), 2.22 - 2.13 (m, 1H), 1.74 - 1.59 (m, 1H), 1.12-1.20 (m, J = 2.9, 6.1,12.3 Hz, 1H); LCMS(電灑) m/z 413.2 (M+H+). | H |
| 352 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.25 - 13.17 (m, 1H), 11.02 (s, 1H), 8.84 (s, 1H), 8.31 - 8.24 (m, 1H), 8.18 (s, 1H), 7.57 - 7.50 (m, 2H), 7.16 (d, J = 7.6 Hz, 1H), 6.80 (br d, J = 3.8 Hz, 1H), 5.07 - 4.78 (m, 1H), 2.92 (br s, 6H), 2.23 - 2.09 (m, 1H), 1.76 - 1.58 (m, 1H), 1.27 - 1.08 (m, 1H); LCMS(電灑) m/z 379.1 (M +H+). | H |
| 353 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.69 (s, 1H), 11.08 (s, 1H), 8.76 (s, 1H), 8.52 (s, 2H), 8.15 (s, 1H), 7.97 (s, 1H), 7.54 (s, 1H), 7.46 (s, 2H), 7.33 (br, 1H), 5.04 - 4.83 (m, 1H), 4.48 (s, 2H), 2.91 (s, 3H), 2.20-2.15 (m, 1H), 1.72 - 1.62 (m, 1H), 1.23 - 1.13 (m, 1H); LCMS (電灑) m/z 508.1 (M+H)+. | H |
| 354 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.45 (s, 1H), 11.10 (s, 1H), 8.71 (s, 1H), 8.20 (s, 1H), 8.09 (s, 1H), 7.52 (t, J=9.7 Hz, 2H), 7.28 (td, J=2.4, 8.9 Hz, 1H), 5.05 - 4.80 (m, 1H), 2.85 (s, 3H), 2.72 (s, 3H), 2.16 (br s, 1H), 1.74 - 1.58 (m, 1H), 1.23 - 1.12 (m, 1H); LCMS(電灑) m/z 425.2 (M+H+). | H |
| 355 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.45 (s, 1H), 11.10 (s, 1H), 8.71 (s, 1H), 8.20 (s, 1H), 8.09 (s, 1H), 7.52 (t, J=9.7 Hz, 2H), 7.28 (td, J=2.4, 8.9 Hz, 1H), 5.05 - 4.80 (m, 1H), 2.85 (s, 3H), 2.72 (s, 3H), 2.16 (br s, 1H), 1.74 - 1.58 (m, 1H), 1.23 - 1.12 (m, 1H); LCMS(電灑) m/z 425.2 (M+H+). | H |
| 356 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.98 (s, 1H), 11.08 (s, 1H), 8.81 (s, 1H), 8.23 - 8.18 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 5.03 - 4.82 (m, 1H), 3.88 (q, J = 7.0 Hz, 2H), 2.17 - 2.14 (m, 1H), 1.70 - 1.63 (m, 1H), 1.19 - 1.16 (m, 1H), 1.10 (t, J = 7.0 Hz, 3H); LCMS(電灑) m/z 416.1 (M +H+). | H |
| 357 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.98 (s, 1H), 11.08 (s, 1H), 8.81 (s, 1H), 8.23 - 8.18 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.8 Hz, 1H), 5.03 - 4.82 (m, 1H), 3.88 (q, J = 7.0 Hz, 2H), 2.17 - 2.14 (m, 1H), 1.70 - 1.63 (m, 1H), 1.19 - 1.16 (m, 1H), 1.10 (t, J = 7.0 Hz, 3H); LCMS(電灑) m/z 416.1 (M +H+). | H |
| 358 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.64 (s, 1H), 11.12 (s, 1H), 8.83 (s, 1H), 8.18 (s, 1H), 8.03 (s, 1H), 7.59 (d, J = 9.6 Hz, 1H), 7.38 (dd, J = 1.6, 9.2 Hz, 1H), 5.03 - 4.84 (m, 1H), 3.83 (t, J = 7.8 Hz, 2H), 3.60 (t, J = 8.0 Hz, 2H), 2.82 (s, 3H), 2.16 (m, 1H), 1.69 - 1.64 (m, 1H), 1.21 - 1.15 (m, 1H) ; LCMS (電灑) m/z 486.10 (M+H)+. | H |
| 359 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.26 (s, 1H), 11.08 (s, 1H), 8.73 (s, 1H), 8.14 (s, 1H), 7.90 (s, 1H), 7.53 (d, J = 9.2 Hz, 1H), 7.32 (dd, J = 1.6, 9.2 Hz, 1 H), 5.16 (dd, J = 2.6, 9.8 Hz, 1H), 5.03 - 4.83 (m, 1H), 4.08 (s, 1H), 2.19 - 2.12 (m, 1H), 1.71 - 1.61 (m, 1H), 1.22 (d, J = 6.8 Hz, 6H), 1.19 - 1.12 (m, 1H) ; LCMS (電灑) m/z 445.10 (M+H)+. | H |
| 360 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (s, 1H), 11.11 (s, 1H), 8.78 (s, 1H), 8.16 (s, 1H), 7.95 (s, 1H), 7.56 (d, J = 9.2 Hz, 1H), 7.36 (dd, J = 1.8, 9.4 Hz, 1H), 5.02 - 4.85 (m, 1H), 3.54 (s, 1H), 2.89 (d, J = 3.2 Hz, 3H), 2.19 - 2.12 (m, 1H), 1.71 - 1.61 (m, 1H), 1.21 - 1.13 (m, 7H) ; LCMS (電灑) m/z 459.10 (M+H)+. | H |
| 361 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.40 (s, 1H), 11.10 (s, 1H), 8.77 (s, 1H), 8.15 (s, 1H), 7.92 (s, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.35 (dd, J = 9.2 Hz, J = 2.0 Hz, 1H), 5.03 - 4.83 (m, 1H), 3.01-2.98 (br, 4H), 2.17-2.14 (m, 1H), 1.69 - 1.62 (m, 1H), 1.19 - 1.14 (m, 1H) 0.64-0.59 (m, 2H), 0.48-0.45 (m, 2H); LCMS (電灑) m/z 457.1 (M+H)+. | H |
| 362 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54 (s, 1H), 11.10 (s, 1H), 8.81 (s, 1H), 8.18 (s, 1H), 7.96 (d, J = 1.6 Hz, 1H), 7.58 (d, J = 9.6 Hz, 1H), 7.35 (dd, J = 1.6, 9.2 Hz, 1H), 5.47 (t, J = 5.6 Hz, 1H), 5.03-4.83 (m, 3H), 2.19 - 2.12 (m, 1H), 1.70 - 1.63 (m, 1H), 1.19 - 1.12 (m, 1H); LCMS (電灑) m/z 419.10 (M+H)+. | H |
| 363 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.90 (s, 1H), 11.12 (s, 1H), 8.85 (s, 1H), 8.18 (s, 1H), 8.07 (d, J = 1.2 Hz, 1H), 7.59 (d, J = 9.6 Hz, 1H), 7.38 (dd, J = 2.0, 9.2 Hz, 1H), 5.93 (s, 1H), 5.81 (s, 1H), 5.04 - 4.83 (m, 1H), 2.19 - 2.12 (m, 1H), 1.71 - 1.61 (m, 1H), 1.19 - 1.13 (m, 1H); LCMS (電灑) m/z 420.05 (M+H)+. | H |
| 364 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.73 (s, 1H), 11.15 (s, 1H), 8.93 (s, 1H), 8.23 (s, 1H), 8.21 (s, 1H), 7.63 (d, J = 9.2 Hz, 1H), 7.45 (d, J = 9.2 Hz, 1H), 5.03 - 4.84 (m, 1H), 2.55 (s, 3H), 2.16-2.14 (m, 1H), 1.69 - 1.63 (m, 1H), 1.20 - 1.15 (m, 1H); LCMS (電灑) m/z 470.10 (M+H)+. | H |
| 365 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.56 - 14.07 (1H), 11.12 (s, 1H), 8.84 (d, J = 1.1 Hz, 1H), 8.20 (s, 1H), 8.17 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.1, 1.9 Hz, 1H), 7.28 (s, 2H), 6.41 (t, J = 2.2 Hz, 2H), 5.04 - 4.84 (m, 1H), 2.20 - 2.13 (m, 1H), 1.70 - 1.64 (m, 1H), 1.20 - 1.13 (m, 1H); LCMS (電灑) m/z 453.10 (M+H)+. | H |
| 366 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.35 (s, 1H), 11.09 (s, 1H), 8.77 (s, 1H), 8.14 (s, 1H), 7.97 (s, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.35 (dd, J = 9.3, 1.6 Hz, 1H), 6.79-6.22 (m, 1H), 5.10-4.47 (m, 3H), 2.25-2.09 (m, 1H), 1.76-1.57 (m, 1H), 1.21-1.09 (m, 1H); LCMS (電灑) m/z 442.10 (M+H)+. | H |
| 367 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.03 (s, 1H), 11.07 (s, 1H), 8.71 (s, 1H), 8.16 (d, J = 13.2 Hz, 1H), 7.86 (s, 1H), 7.53 (d, J = 9.3 Hz, 1H), 7.30 (dd, J = 8.8, 1.6 Hz, 1H), 6.08 (s, 1H), 5.09 - 4.81 (m, 1H), 3.12 (s, 1H), 2.17-2.08 (m, 1H), 1.66 (d, J = 23.1 Hz, 1H), 1.23-1.14 (m, 1H), 0.80 (d, J = 5.5 Hz, 2H), 0.63 (d, J = 3.3 Hz, 2H); LCMS(電灑) m/z 443.1 (M+H+). | H |
| 368 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.96 (s, 1H), 11.12 (s, 1H), 8.93-8.83 (m, 1H), 8.17-8.12 (m, 2H), 7.69-7.57 (m, 1H), 7.46-7.36 (m, 1H), 5.04-4.83 (m, 1H), 3.44 (qd, J = 7.2, 3.7 Hz, 1H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.23-1.13 (m, 1H), 0.98-0.55 (m, 4H); LCMS(電灑) m/z 539.1 (M+H+). | H |
| 369 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.16 (s, 1H), 11.11 (s, 1H), 10.16 (s, 1H), 8.83 (d, J = 1.1 Hz, 1H), 8.18 (s, 1H), 7.98 (d, J = 1.6 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 4.93 (ddd, J = 66.2, 9.9, 6.3 Hz, 1H), 4.76 (t, J = 5.5 Hz, 1H), 3.79 (q, J = 6.2 Hz, 2H), 2.65 (t, J = 6.6 Hz, 2H), 2.19-2.08 (m, 1H), 1.70-1.61 (m, 1H), 1.23-1.13 (m, 1H); LCMS(電灑) m/z 475.1 (M+H+). | H |
| 370 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.12 - 13.48 (1H), 11.08 (s, 1H), 8.72 (s, 1H), 8.14 (s, 1H), 7.90 (s, 1H), 7.52 (d, J = 9.3 Hz, 1H), 7.31 (dd, J = 9.1, 1.9 Hz, 1H), 5.16 (d, J = 6.9 Hz, 1H), 5.03 - 4.83 (m, 1H), 3.90 (s, 1H), 2.19 - 2.12 (m, 1H), 1.71 - 1.58 (m, 2H), 1.53 - 1.46 (m, 1H), 1.23 - 1.12 (m, 4H), 0.94 (t, J = 7.4 Hz, 3H); LCMS (電灑) m/z 459.10 (M+H)+. | H |
| 371 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38 (s, 1H), 11.10 (s, 1H), 8.77 (d, J = 12.6 Hz, 1H), 8.14 (d, J = 8.2 Hz, 1H), 7.97 (s, 1H), 7.54 (t, J = 9.3 Hz, 1H), 7.35 (d, J = 9.3 Hz, 1H), 6.66-6.46 (m, 0.5H), 6.11 (d, J = 9.3 Hz, 1H), 5.99-5.80 (m, 0.5H), 5.10-4.77 (m, 2H), 2.24-2.09 (m, 1H), 1.81-1.58 (m, 4H), 1.21-1.06 (m, 1H); LCMS (電灑) m/z 456.10 (M+H)+. | H |
| 372 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.28 (s, 1H), 11.11 (s, 1H), 8.80 (t, J = 1.4 Hz, 1H), 8.18 (s, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 9.1, 1.9 Hz, 1H), 5.83 (d, J = 3.8 Hz, 1H), 5.43-5.37 (m, 1H), 5.04-4.83 (m, 1H), 2.19-2.12 (m, 1H), 1.70-1.62 (m, 1H), 1.54 (d, J = 6.6 Hz, 3H), 1.23-1.13 (m, 1H); LCMS (電灑) m/z 433.10 (M+H)+. | H |
| 373 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.40 (s, 1H), 11.11 (s, 1H), 8.82 (t, J = 1.4 Hz, 1H), 8.17 (s, 1H), 7.99 (s, 1H), 7.61-7.57 (m, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 5.07-4.83 (m, 2H), 3.23 (s, 3H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.57 (t, J = 6.3 Hz, 4H), 1.21-1.13 (m, 2H); LCMS (電灑) m/z 447.10 (M+H)+. | H |
| 374 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.68 (s, 1H), 11.11 (s, 1H), 8.83 (t, J = 1.4 Hz, 1H), 8.18 (s, 1H), 8.05 (s, 1H), 7.61-7.58 (m, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 6.43-6.27 (m, 1H), 5.04-4.83 (m, 1H), 2.20-2.13 (m, 1H), 1.83 (dd, J = 23.9, 6.3 Hz, 3H), 1.72-1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (電灑) m/z 435.10 (M+H)+. | H |
| 375 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.37 (s, 1H), 11.44 (s, 1H), 11.11 (s, 1H), 8.82 (d, J = 1.1 Hz, 1H), 8.18 (s, 1H), 8.01 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.49 (s, 1H), 7.39 (dd, J = 9.1, 1.9 Hz, 1H), 7.01 (s, 1H), 6.68 (s, 1H), 5.04-4.84 (m, 1H), 2.20-2.13 (m, 1H), 1.71-1-61 (m, 1H), 1.23-1.13 (m, 1H) ; LCMS (電灑) m/z 454.10 (M+H)+. | H |
| 376 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.35 (s, 1H), 11.11 (s, 1H), 8.82 (d, J = 1.6 Hz, 1H), 8.18 (s, 1H), 8.01 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.46 (s, 1H), 7.38 (dd, J = 9.1, 1.9 Hz, 1H), 6.96 (s, 1H), 6.64 (s, 1H), 5.04-4.83 (m, 1H), 3.75 (s, 3H), 2.20-2.13 (m, 1H), 1.71-1.61 (m, 1H), 1.23-1.13 (m, 1H); LCMS (電灑) m/z 468.10 (M+H)+. | H |
| 377 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (s, 1H), 11.12 (s, 1H), 8.87 (t, J = 1.4 Hz, 1H), 8.19 (s, 1H), 8.04 (s, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.42 (dd, J = 9.1, 1.9 Hz, 1H), 7.08 (s, 1H), 6.39-6.37 (m, 1H), 6.26 (t, J = 3.0 Hz, 1H), 5.04-4.84 (m, 1H), 3.54 (d, J = 1.1 Hz, 3H), 2.20-2.13 (m, 1H), 1.72-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (電灑) m/z 468.10 (M+H)+. | H |
| 378 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.57 (s, 1H), 11.12 (s, 1H), 8.88 (t, J = 1.1 Hz, 1H), 8.21 (s, 1H), 8.10 (s, 1H), 7.70 (d, J = 1.6 Hz, 1H), 7.62 (d, J = 9.3 Hz, 1H), 7.43 (dd, J = 9.1, 1.9 Hz, 1H), 6.64 (d, J = 1.4 Hz, 1H), 5.04-4.84 (m, 1H), 3.76 (s, 3H), 2.20-2.13 (m, 1H), 1.71-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (電灑) m/z 469.10 (M+H)+. | H |
| 379 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.94 (s, 1H), 11.11 (s, 1H), 9.01 (s, 1H), 8.86 (s, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.59 (d, J = 9.1 Hz, 1H), 7.39 (dd, J = 9.2, 1.5 Hz, 1H), 6.36 (s, 2H), 5.02 - 4.85 (m, 1H), 2.18 - 2.14 (m, 1H), 1.70 - 1.63 (m, 1H), 1.20 - 1.14 (m, 1H); LCMS (電灑) m/z 470.10 (M+H)+. | I |
| 380 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.56 (s, 1H), 11.10 (s, 1H), 8.82 (d, J = 1.1 Hz, 1H), 8.17 (s, 1H), 7.96 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.36 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 1H), 3.91 (d, J = 1.1 Hz, 2H), 3.20 (q, J = 6.8 Hz, 4H), 2.19-2.12 (m, 1H), 2.00-1.93 (m, 2H), 1.71-1.61 (m, 1H), 1.23-1.13 (m, 1H); LCMS (電灑) m/z 457.10 (M+H)+. | H |
| 381 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.50 (s, 1H), 11.11 (s, 1H), 8.82 (d, J = 1.1 Hz, 1H), 8.18 (s, 1H), 7.98 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.84 (m, 1H), 4.00 (d, J = 1.1 Hz, 2H), 2.53-2.49 (m, 4H), 2.20-2.13 (m, 1H), 1.70-1.62 (m, 5H), 1.24-1.13 (m, 1H); LCMS (電灑) m/z 472.10 (M+H)+. | H |
| 382 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.41 (s, 1H), 11.11 (s, 1H), 8.83 (t, J = 1.1 Hz, 1H), 8.17 (s, 1H), 7.97 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.38 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 1H), 3.84 (s, 2H), 2.44 (s, 4H), 2.19-2.12 (m, 1H), 1.70-1.62 (m, 1H), 1.51-1.37 (m, 6H), 1.23-1.13 (m, 1H); LCMS (電灑) m/z 486.10 (M+H)+. | H |
| 383 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.92 (s, 1H), 11.11 (s, 1H), 8.85 (d, J = 1.1 Hz, 1H), 8.17 (s, 1H), 8.07 (s, 1H), 7.81 (s, 2H), 7.58 (d, J = 9.3 Hz, 1H), 7.38 (dd, J = 9.1, 1.9 Hz, 1H), 6.07 (s, 2H), 5.04 - 4.83 (m, 1H), 2.19 - 2.12 (m, 1H), 1.71 - 1.61 (m, 1H), 1.21 - 1.13 (m, 1H); LCMS (電灑) m/z 469.10 (M+H)+. | I |
| 384 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.95 (s, 1H), 11.11 (s, 1H), 8.83 (t, J = 1.4 Hz, 1H), 8.31 (d, J = 1.4 Hz, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.75 (d, J = 1.1 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 6.03 (s, 2H), 5.04 - 4.83 (m, 1H), 2.19 - 2.12 (m, 1H), 1.71 - 1.61 (m, 1H), 1.21 - 1.13 (m, 1H); LCMS (電灑) m/z 469.10 (M+H)+. | I |
| 385 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.92 (s, 1H), 11.11 (s, 1H), 8.83 (d, J = 1.1 Hz, 1H), 8.79 (s, 1H), 8.16 (s, 1H), 8.07 (s, 1H), 7.96 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 5.83 (s, 2H), 5.04 - 4.83 (m, 1H), 2.19 - 2.12 (m, 1H), 1.71 - 1.61 (m, 1H), 1.21 - 1.13 (m, 1H); LCMS (電灑) m/z 469.10 (M+H)+. | I |
| 386 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.86 (s, 1H), 11.12 (s, 1H), 8.85 (s, 1H), 8.17 (s, 1H), 8.08 (s, 1H), 7.58 (d, J = 9.6 Hz, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 7.33 (d, J = 1.1 Hz, 1H), 6.93-6.91 (m, 1H), 5.04-4.83 (m, 1H), 3.80 (d, J = 15.4 Hz, 3H), 2.19-2.12 (m, 1H), 1.70-1.62 (m, 1H), 1.23-1.13 (m, 1H); LCMS (電灑) m/z 501.10 (M+H)+. | H |
| 387 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.20 - 13.84 (s, 1 H) 8.84 (s, 1 H) 8.71 (d, J=9.4 Hz, 1 H) 7.92 (s, 1 H) 7.87 (s, 1 H) 7.49 (d, J=9.13 Hz, 1 H) 7.27 (dd, J=9.26, 1.75 Hz, 1 H) 6.87 (br s, 1 H) 3.00 (d, J=2.38 Hz, 6 H) 2.66 - 2.70 (m, 1 H) 0.61 - 0.71 (m, 2 H) 0.39 - 0.46 (m, 2 H); LCMS (電灑) m/z 428.1 (M+H+). | H |
| 388 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.12 (s, 1H), 8.89 (s, 1H), 8.21 (s, 1H), 8.15 (s, 1H), 7.62 (d, J=9.2 Hz, 1H), 7.44 (dd, J=1.6, 9.3 Hz, 1H), 6.95 (br s, 1H), 6.27 (t, J=3.1 Hz, 1H), 6.14 (br s, 1H), 5.13 - 4.80 (m, 1H), 2.18 (td, J=7.0, 13.9 Hz, 1H), 2.07 (s, 3H), 1.74 - 1.61 (m, 1H), 1.23 - 1.13 (m, 1H); LCMS (電灑) m/z 467.1 (M +H+). | H |
| 389 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 - 11.96 (m, 1H), 11.08 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.89 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.35 (dd, J = 1.7, 9.2 Hz, 1H), 6.56 - 5.57 (m, 1H), 5.21 - 4.65 (m, 1H), 2.25 - 2.09 (m, 1H), 1.69 (d, J = 1.4 Hz, 6H), 1.65 - 1.59 (m, 1H), 1.17 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS (電灑) m/z 446.0 (M+H+). | H |
| 390 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.66 (s, 1H), 11.11 (s, 1H), 8.83 (s, 1H), 8.18 (s, 1H), 8.00 (d, J = 1.1 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 3H), 3.36 (s, 3H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.23-1.13 (m, 1H); LCMS (電灑) m/z 432.10 (M+H)+. | H |
| 391 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.65 (s, 1H), 11.11 (s, 1H), 8.83 (d, J = 1.1 Hz, 1H), 8.18 (s, 1H), 8.00 (d, J = 1.6 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 3H), 3.57 (q, J = 7.1 Hz, 2H), 2.19-2.12 (m, 1H), 1.66 (dtd, J = 23.3, 6.7, 3.5 Hz, 1H), 1.39 (s, 0H), 1.24-1.13 (m, 4H); LCMS (電灑) m/z 446.10 (M+H)+. | H |
| 392 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.76-14.21 (1H), 11.11 (s, 1H), 9.64 (s, 1H), 8.84 (s, 1H), 8.17 (s, 1H), 8.09 (s, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.38 (d, J = 8.8 Hz, 1H), 6.11 (s, 2H), 5.01 - 4.85 (m, 1H), 2.19 - 2.12 (m, 1H), 1.69 - 1.63 (m, 1H), 1.19 - 1.13 (m, 1H); LCMS (電灑) m/z 470.10 (M+H)+. | I |
| 393 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54-13.94 (s, 1H), 11.06 (d, J = 7.7 Hz, 1H), 8.98 (d, J = 11.5 Hz, 1H), 8.80 (s, 1H), 8.12 (s, 2H), 7.58-7.54 (m, 1H), 7.35 (dd, J = 9.3, 1.6 Hz, 1H), 6.74 (q, J = 7.1 Hz, 1H), 5.00-4.79 (m, 1H), 2.24-2.20 (m, 3H), 2.16-2.09 (m, 1H), 1.68-1.57 (m, 1H), 1.18-1.09 (m, 1H); LCMS (電灑) m/z 485.10 (M+H)+. | I |
| 394 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (s, 1H), 11.06 (d, J = 6.6 Hz, 1H), 8.71 (d, J = 7.7 Hz, 1H), 8.13 (d, J = 7.7 Hz, 1H), 7.88 (d, J = 1.1 Hz, 1H), 7.52 (t, J = 8.5 Hz, 1H), 7.31 (dd, J = 9.3, 1.6 Hz, 1H), 5.56-5.52 (m, 1H), 5.03-4.82 (m, 2H), 3.09 (s, 3H), 2.85 (s, 3H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.34 (d, J = 6.6 Hz, 3H), 1.21-1.12 (m, 1H); LCMS (電灑) m/z 503.15 (M+H)+. | H |
| 395 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.01 (s, 1H), 11.09 (s, 1H), 8.81 (s, 1H), 8.16 (s, 1H), 7.94 (s, 1H), 7.58 (d, J=9.3 Hz, 1H), 7.37 (dd, J=1.7, 9.3 Hz, 1H), 5.08 - 4.80 (m, 1H), 3.18 (s, 3H), 2.15 (br d, J=7.0 Hz, 1H), 1.71 (br d, J=2.7 Hz, 6H), 1.64 (br s, 1H), 1.17 (br dd, J=8.9, 12.1 Hz, 1H); LCMS (電灑) m/z 460.2 (M+H)+. | H |
| 396 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.37- 12.98 (m, 1H), 11.09 (s, 1H), 8.82 (s, 1H), 8.22 (s, 1H), 8.16 (s, 1H), 7.95 (s, 1H), 7.57 (d, J= 9.2 Hz, 1H), 7.37 (dd, J= 1.7, 9.2 Hz, 1H), 5.03 - 4.82 (m, 1H), 3.87 (q, J= 6.6 Hz, 1H), 2.21 (s, 6H), 2.16 (br dd, J = 6.1, 7.6 Hz, 1H), 1.72- 1.61 (m, 1H), 1.49 (d, J= 6.8 Hz, 3H), 1.23 - 1.13 (m, 1H); LCMS (電灑) m/z 459.2 (M+H)+. | H |
| 397 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.26-13.88 (1H), 11.08 (s, 1H), 8.71 (d, J = 1.6 Hz, 1H), 8.15 (s, 1H), 7.94 (s, 1H), 7.53 (d, J = 9.3 Hz, 1H), 7.30 (dd, J = 9.3, 1.6 Hz, 1H), 5.75 (d, J = 3.3 Hz, 1H), 5.03-4.83 (m, 1H), 4.42 (d, J = 4.4 Hz, 2H), 3.02 (s, 3H), 2.88 (s, 3H), 2.19-2.12 (m, 1H), 1.71-1.61 (m, 1H), 1.23-1.12 (m, 1H); LCMS (電灑) m/z 488.1 (M+H)+. | H |
| 398 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.53-14.00 (1H), 11.12 (s, 1H), 9.77 (s, 1H), 8.83 (s, 1H), 8.20-8.17 (m, 2H), 7.59 (d, J = 9.1 Hz, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 6.59 (q, J = 7.1 Hz, 1H), 5.04-4.83 (m, 1H), 2.21 (d, J = 7.1 Hz, 3H), 2.17-2.12 (m, 1H), 1.70-1.63 (m, 1H), 1.20-1.13 (m, 1H); LCMS (電灑) m/z 484.10 (M+H)+. | I |
| 399 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.10 (s, 1H), 8.79 (s, 1H), 8.20 (d, J = 15.8 Hz, 2H), 8.00 (s, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.34 (dd, J = 1.8, 9.2 Hz, 1H), 5.03 - 4.84 (m, 1H), 4.81 - 4.75 (m, 1H), 2.22 - 2.09 (m, 1H), 1.75 - 1.59 (m, 1H), 1.54 (d, J = 6.8 Hz, 3H), 1.27 - 1.12 (m, 1H); LCMS (電灑) m/z 431.1 (M+H)+. | H |
| 400 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.12-13.82 (m, 1H), 11.11 (s, 1H), 8.84 (s, 1H), 8.27-8.14 (m, 1H), 7.64 (s, 1H), 7.61 (d, J = 9.2 Hz, 1H), 7.39 (dd, J = 9.1, 1.8 Hz, 1H), 7.27 (s, 1H), 6.66 (dd, J = 2.9, 1.6 Hz, 1H) 5.10 - 4.79 (m, 1H), 3.22-3.00 (m, 6H), 2.21 - 2.12 (m, 1H), 1.74 - 1.61 (m, 1H), 1.24 - 1.12 (m, 1H); LCMS (電灑) m/z 524.1 (M+H)+. | H |
| 401 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.79 (s, 1 H) 11.18 (s, 1 H) 8.67 (d, J=7.09 Hz, 1 H) 7.93 (s, 1 H) 7.77 (s, 1 H) 6.92 - 6.99 (m, 2 H) 4.82 - 5.08 (m, 1 H) 4.53 (s, 1 H) 2.15 (m, 1 H) 1.61 - 1.75 (m, 1 H) 1.12 - 1.27 (m, 1 H) 0.92 (br s, 2 H) 0.68 - 0.77 (m, 2 H); LCMS (電灑) m/z 444.0 (M+H)+. | H |
| 402 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.08 (s, 1H), 8.81 (s, 1H), 8.27 (br s, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 1.7, 9.3 Hz, 1H), 5.12 - 4.75 (m, 1H), 4.33 (d, J = 6.8 Hz, 1H), 2.22 - 2.12 (m, 4H), 1.74 - 1.59 (m, 1H), 1.47 (d, J = 6.7 Hz, 3H), 1.22 - 1.12 (m, 1H); LCMS (電灑) m/z 445.2 (M+H)+. | H |
| 403 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.35 - 13.11 (m, 1H), 10.33 (s, 1H), 8.40 (s, 1H), 7.96 - 7.72 (m, 1H), 7.44 (s, 2H), 6.36 (d, J = 1.4 Hz, 1H), 5.79 (s, 2H), 5.09 (dd, J = 2.4, 9.4 Hz, 1H), 5.05 - 4.81 (m, 1H), 4.17 - 3.92 (m, 1H), 4.14 - 2.74 (m, 1H), 2.17 - 2.05 (m, 1H), 1.71 - 1.55 (m,12H), 1.23 (d, J = 6.3 Hz, 6H), 1.21 - 1.08 (m, 1H); LCMS (電灑) m/z 460.2 (M+H)+. | H |
| 404 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.17 - 13.33 (m, 1H), 11.08 (s, 1H), 8.79 (s, 1H), 8.16 (s, 1H), 8.00 (s, 1H), 7.56 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.5, 9.2 Hz, 1H), 5.06 - 4.81 (m, 1H), 4.73 (br d, J = 1.1 Hz, 1H), 2.16 (td, J = 6.9, 13.8 Hz, 1H), 2.07 (s, 1H), 1.76 - 1.56 (m, 1H), 1.37 (d, J = 6.0 Hz, 6H), 1.17 (tdd, J = 6.2, 9.0, 12.3 Hz, 1H); LCMS (電灑) m/z 446.1 (M+H)+. | H |
| 405 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.55 (br s, 1H), 11.08 (s, 1H), 8.78 (d, J=1.0 Hz, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.57 (d, J=9.3 Hz, 1H), 7.35 (dd, J=1.8, 9.3 Hz, 1H), 5.05 - 4.80 (m, 1H), 3.67 - 3.55 (m, 1H), 2.16 (td, J=7.0, 14.0 Hz, 1H), 1.73 - 1.59 (m, 1H), 1.45 (d, J=7.0 Hz, 6H), 1.17 (tdd, J=6.1, 9.1, 12.1 Hz, 1H); LCMS (電灑) m/z 430.2 (M+H)+. | H |
| 406 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54 (s, 1H), 11.11 (s, 1H), 8.79 (s, 1H), 8.17 (s, 1H), 7.96 (d, J = 1.1 Hz, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 1H), 3.61 (q, J = 8.8 Hz, 1H), 2.19-1.91 (m, 8H), 1.73-1.61 (m, 3H), 1.24-1.07 (m, 1H); LCMS (電灑) m/z 456.10 (M+H)+. | H |
| 407 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.18 - 13.49 (m, 1H), 11.09 (s, 1H), 9.02 (s, 1H), 8.83 (s, 1H), 8.28 - 7.99 (m, 2H), 7.58 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 1.7, 9.2 Hz, 1H), 6.78 (q, J = 6.9 Hz, 1H), 5.10 - 4.74 (m, 1H), 2.27 (d, J = 7.0 Hz, 3H), 2.21 - 2.11 (m, 1H), 1.74 - 1.59 (m, 1H), 1.22 - 1.12 (m, 1H); LCMS (電灑) m/z 484.1 (M+H)+. | I |
| 408 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.19 - 13.48 (m, 1H), 11.09 (s, 1H), 9.02 (s, 1H), 8.83 (s, 1H), 8.31 - 7.98 (m, 2H), 7.59 (d, J = 9.2 Hz, 1H), 7.38 (dd, J = 1.7, 9.2 Hz, 1H), 6.78 (q, J = 7.1 Hz, 1H), 5.09 - 4.68 (m, 1H), 2.27 (d, J = 7.0 Hz, 3H), 2.20 - 2.10 (m, 1H), 1.67 (tdd, J = 3.2, 6.8, 19.9 Hz, 1H), 1.23 - 1.13 (m, 1H); LCMS (電灑) m/z 484.1 (M+H)+. | I |
| 409 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38 (s, 1H), 11.10 (s, 1H), 8.86 (s, 1H), 8.17 (s, 1H), 8.01 (d, J = 1.6 Hz, 1H), 7.59 (q, J = 9.7 Hz, 2H), 7.40 (dd, J = 9.3, 1.6 Hz, 1H), 5.82-5.75 (m, 1H), 5.04-4.83 (m, 1H), 2.20-2.13 (m, 1H), 1.72-1.62 (m, 1H), 1.28-1.11 (m, 1H); LCMS (電灑) m/z 487.1 (M+H)+. | H |
| 410 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.51 (s, 1H), 11.08 (s, 1H), 8.77 (s, 1H), 8.18 (s, 1H), 7.95 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.34 (dd, J = 9.3, 1.6 Hz, 1H), 5.03-4.83 (m, 2H), 4.50-4.42 (m, 3H), 3.51-3.38 (m, 6H), 2.20-2.07 (m, 3H), 1.99-1.83 (m, 3H), 1.72-1.61 (m, 2H), 1.23-1.13 (m, 4H); LCMS (電灑) m/z 472.10 (M+H)+. | H |
| 411 |  | 1H NMR (400 MHz, DMSO-d 6) δ 8.62 - 8.72 (m, 1 H) 8.12 - 8.25 (m, 1 H) 7.83 - 7.96 (m, 1 H) 7.56 - 7.62 (m, 1 H) 7.43 - 7.52 (m, 1 H) 4.95 - 4.98 (m, 0.5 H) 4.77 - 4.81 (m, 0.5 H) 2.70 - 2.80 (m, 3 H) 2.07 - 2.17 (m, 1 H) 1.73 - 1.88 (m, 1 H) 1.18 - 1.31 (m, 1 H); LCMS (電灑) m/z 461.3 (M+H)+. | H |
| 412 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54 - 12.76 (m, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.36 (s, 1H), 8.17 (s, 1H), 8.07 - 7.97 (m, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.36 (br d, J = 9.0 Hz, 1H), 7.23 (br d, J = 6.8 Hz, 1H), 6.87 (br d, J = 5.0 Hz, 1H), 6.07 (q, J = 6.7 Hz, 1H), 5.82 - 5.67 (m, 1H), 5.13 - 4.80 (m, 1H), 3.02 (s, 3H), 2.78 (br s, 1H), 2.20 - 2.14 (m, 1H), 2.10 - 2.00 (m, 3H), 1.86 - 1.75 (m, 1H), 1.71 - 1.64 (m, 3H), 1.28 - 1.07 (m, 1H); LCMS (電灑) m/z 487.1 (M+H)+. | H |
| 413 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.10 (s, 1H), 9.77 (s, 1H), 8.82 (s, 1H), 8.24 - 8.00 (m, 2H), 7.58 (d, J = 9.1 Hz, 1H), 7.37 (dd, J = 1.6, 9.3 Hz, 1H), 6.62 (d, J = 7.4 Hz, 1H), 5.11 - 4.74 (m, 1H), 2.25 - 2.15 (m, 4H), 1.79 - 1.56 (m, 1H), 1.27 - 1.10 (m, 1H); LCMS (電灑) m/z 484.1 (M+H)+. | I |
| 414 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.75 (br s, 1H), 11.09 (s, 1H), 9.75 (s, 1H), 8.82 (s, 1H), 8.17 (s, 1H), 8.08 (s, 1H), 7.59 (br d, J = 8.9 Hz, 1H), 7.37 (dd, J = 1.7, 9.2 Hz, 1H), 6.59 (br d, J = 6.8 Hz, 1H), 5.12 - 4.75 (m, 1H), 2.26 - 2.07 (m, 4H), 1.75 - 1.60 (m, 1H), 1.21 - 1.15 (m, 1H); LCMS (電灑) m/z 484.1 (M+H)+. | I |
| 415 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.40-13.49 (1H), 11.06-11.17 (1H), 8.83-8.91 (1H), 8.15-8.21 (1H), 8.02-8.09 (1H), 7.57-7.64 (1H), 7.38-7.46 (1H), 5.72-5.82 (1H), 4.82-5.07 (1H), 3.46-3.55 (3H), 2.12-2.21 (1H), 1.61-1.74 (1H), 1.13-1.22 (1H); LCMS (電灑) m/z 501.1 (M+H)+. | H |
| 416 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.23 (s, 1H), 11.06 (s, 1H), 8.72 (s, 1H), 8.16 (s, 1H), 7.88 (d, J = 1.1 Hz, 1H), 7.54 (d, J = 9.3 Hz, 1H), 7.32 (dd, J = 9.3, 1.6 Hz, 1H), 5.60-5.58 (m, 1H), 5.04-4.83 (m, 1H), 4.55 (s, 1H), 3.95 (q, J = 7.7 Hz, 1H), 3.87 (dd, J = 9.1, 5.8 Hz, 1H), 3.79-3.71 (m, 2H), 2.27-2.13 (m, 2H), 1.91 (s, 1H), 1.67 (dtd, J = 23.5, 6.9, 3.7 Hz, 1H), 1.22-1.13 (m, 1H); LCMS (電灑) m/z 474.1 (M+H)+. | H |
| 417 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.67 - 13.49 (m, 1H), 11.10 (s, 1H), 8.79 (s, 1H), 8.52 (d, J = 6.8 Hz, 1H), 8.16 (s, 1H), 7.98 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.6, 9.3 Hz, 1H), 5.45 (quin, J = 7.1 Hz, 1H), 5.07 - 4.81 (m, 1H), 2.22 - 2.11 (m, 1H), 1.85 (s, 3H), 1.73 - 1.61 (m, 1H), 1.55 (d, J = 7.3 Hz, 3H), 1.17 (tdd, J = 6.3, 9.1, 12.3 Hz, 1H); LCMS (電灑) m/z 473.2 (M+H)+. | H |
| 418 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.40 (s, 1H), 11.10 (s, 1H), 8.87 (s, 1H), 8.16-8.04 (m, 2H), 7.59 (d, J = 8.8 Hz, 1H), 7.41 (dd, J = 9.1, 1.9 Hz, 1H), 5.81 (q, J = 7.1 Hz, 1H), 5.04-4.83 (m, 1H), 3.79-3.58 (m, 2H), 2.20-2.13 (m, 1H), 1.67 (dtd, J = 23.4, 6.8, 3.6 Hz, 1H), 1.23 (t, J = 7.1 Hz, 3H), 1.19-1.13 (m, 1H); LCMS (電灑) m/z 514.7 (M+H)+. | H |
| 419 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.78 (s, 1H), 11.12 (s, 1H), 8.89 (t, J = 1.4 Hz, 1H), 8.18 (s, 1H), 8.12 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.42 (dd, J = 9.1, 1.9 Hz, 1H), 7.06 (dt, J = 41.2, 6.7 Hz, 1H), 5.05-4.84 (m, 1H), 2.21-2.14 (m, 1H), 1.68 (dtd, J = 23.5, 6.9, 3.5 Hz, 1H), 1.24-1.14 (m, 1H); LCMS (電灑) m/z 488.7 (M+H)+. | H |
| 420 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.30 (br s, 1H), 11.05 (s, 1H), 8.72 (s, 1H), 8.14 (s, 1H), 7.87 (br s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.31 (dd, J = 1.5, 9.2 Hz, 1H), 5.34 (br s, 1H), 5.04 - 4.82 (m, 1H), 2.16 (td, J = 7.0, 13.9 Hz, 1H), 1.73 - 1.61 (m, 1H), 1.26 (d, J = 6.3 Hz, 3H), 1.16 (ddd, J = 2.8, 6.2, 12.1 Hz, 1H), 1.00 (br s, 1H), 0.46 - 0.37 (m, 2H), 0.30 - 0.20 (m, 2H); LCMS (電灑) m/z 471.2 (M+H)+. | H |
| 421 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.22 (br s, 1H), 11.06 (s, 1H), 8.71 (s, 1H), 8.14 (s, 1H), 7.86 (s, 1H), 7.52 (d, J = 9.1 Hz, 1H), 7.30 (d, J = 9.3 Hz, 1H), 5.57 (m, 1H), 4.92 (m, 1H), 3.30 (s, 2H), 2.15 (m, 1H), 1.66 (m, 1H), 1.16 (m, 1H), 1.07 (m, 1H), 0.48 (m, 2H), 0.27 (m, 2H); LCMS (電灑) m/z 457.1 (M+H)+. | H |
| 422 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.52 - 13.66 (m, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.16 (s, 1H), 7.97 (s, 1H), 7.57 (d, J=9.2 Hz, 1H), 7.36 (dd, J=1.6 Hz, 1.6 Hz, 1H), 5.04 –4.83 (m, 1H), 3.82 –3.74 (m, 3H), 3.68 (s, 1H), 2.20-2.14 (m, 1H), 1.71-1.63 (m, 1H), 1.22 (d, J = 7.4 Hz, 3H), 1.2-1.14(m, 2H); LCMS (電灑) m/z 460.0 (M+H)+; SFC RT=0.640. | H |
| 423 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.57 (s, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.16 (s, 1H), 7.98 (s, 1H), 7.57 (d, J=9.2Hz, 1H), 7.35 (d, J=1.6 Hz, 1H), 5.04 –4.83 (m, 1H), 3.82 –3.74 (m, 3H), 2.20-2.14 (m, 1H), 1.41-1.39 (m, 1H), 1.22 (d, J = 14.4 Hz, 3H), 1.2-1.17(m, 2H); LCMS (電灑) m/z 460.0 (M+H)+; SFC RT=1.252. | H |
| 424 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.64 - 13.32 (m, 1H), 11.09 (s, 1H), 8.79 (s, 1H), 8.32 (br d, J = 6.3 Hz, 1H), 8.16 (s, 1H), 7.98 (s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.7, 9.2 Hz, 1H), 5.46 (br t, J = 7.0 Hz, 1H), 5.05 - 4.81 (m, 1H), 2.19 - 2.07 (m, 3H), 1.74 - 1.60 (m, 1H), 1.55 (d, J = 7.3 Hz, 3H), 1.24 - 1.11 (m, 1H), 0.95 (t, J = 7.6 Hz, 3H); LCMS (電灑) m/z 487.2 (M+H)+. | H |
| 425 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.55-13.09 (m, 1H), 11.07 (s, 1H), 8.73 (s, 1H), 8.16 (s, 1H), 8.07-7.83 (m, 1H), 7.54 (d, J = 9.1 Hz, 1H), 7.32 (dd, J = 1.7, 9.1 Hz, 1H), 6.30-5.95 (m, 1H), 5.65 - 5.44 (m, 1H), 5.11-4.76 (m, 1H), 4.54-3.95 (m, 1H), 2.20-2.12 (m, 1H), 1.75-1.59 (m, 1H), 1.33 (d, J = 6.7 Hz, 3H), 1.17 (ddt J = 6.2, 6.2, 9.1, 12.2 Hz, 1H); LCMS (電灑) m/z 481.0 (M+H)+. | H |
| 426 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.66 - 13.47 (m, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.67 (br d, J = 6.8 Hz, 1H), 8.16 (s, 1H), 8.06 (s, 1H), 8.00 (br s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 1.4, 9.3 Hz, 1H), 5.62 - 5.48 (m, 1H), 5.09 - 4.80 (m, 1H), 2.16 (quin, J = 6.9 Hz, 1H), 1.73 - 1.61 (m, 1H), 1.57 (d, J = 7.0 Hz, 3H), 1.22 - 1.10 (m, 1H); LCMS (電灑) m/z 458.9 (M+H)+. | H |
| 427 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.74 - 13.07 (m, 1H), 11.09 (s, 1H), 8.80 (s, 1H), 8.43 (s, 1H), 8.16 (s, 1H), 7.96 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.35 (dd, J = 1.7, 9.2 Hz, 1H), 5.06 - 4.80 (m, 1H), 4.60 (t, J = 6.4 Hz, 1H), 4.50 - 4.39 (m, 2H), 4.32 (t, J = 6.5 Hz, 1H), 4.15 (t, J = 6.2 Hz, 1H), 3.75 (br t, J = 6.7 Hz, 1H), 2.22 - 2.11 (m, 1H), 1.73 - 1.60 (m, 1H), 1.49 (d, J = 6.7 Hz, 3H), 1.24 - 1.11 (m, 1H); LCMS (電灑) m/z 487.3 (M+H)+. | H |
| 428 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.30 (br s, 1H), 11.19 (s, 1H), 10.04 (d, J = 4.5 Hz, 1H), 8.84 (s, 1H), 8.16 (s, 1H), 8.04 (s, 1H), 7.62 (d, J = 9.1 Hz, 1H), 7.49-7.39 (m,1H), 5.70-5.46 (m, 1H), 5.11 - 4.78 (m, 1H), 2.17 (td, J = 6.9, 13.8 Hz, 1H), 1.69 (d, J = 7.0 Hz, 3H), 1.67-1.59 (m, 1H), 1.29-1.09 (m, 1H); LCMS (電灑) m/z 527.1 (M+H)+. | H |
| 429 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.30 (br s, 1H), 11.05 (s, 1H), 8.72 (s, 1H), 8.14 (s, 1H), 7.91 (s, 1H), 7.58 (d, J = 9.0 Hz, 1H), 7.38-7.32 (m, 1H), 5.09 - 4.81 (m, 1H), 4.08-3.99 (m,1H), 2.19-2.13 (m,1H), 1.71-1.62 (m, 1H), 1.51 (d, J = 6.7 Hz, 3H), 1.32-1.23 (m,1H), 1.21-1.13 (m, 1H), 1.04-0.94 (m,1H), 0.69-0.56 (m, 1H); LCMS (電灑) m/z 496.3 (M+H)+. | H |
| 430 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.99 - 13.36 (m, 1H), 11.09 (s, 1H), 8.79 (s, 1H), 8.51 - 8.44 (m, 1H), 8.46 (s, 1H), 8.41 (br d, J = 6.7 Hz, 1H), 8.15 (s, 1H), 7.97 (s, 1H), 7.57 (d, J = 9.2 Hz, 1H), 7.35 (dd, J = 1.7, 9.3 Hz, 1H), 5.45 (br t, J = 7.0 Hz, 1H), 5.07 - 4.76 (m, 1H), 3.14 - 3.03 (m, 1H), 2.10 (br d, J = 8.7 Hz, 1H), 2.21 - 2.01 (m, 1H), 2.00 - 1.81 (m, 4H), 1.64 (dt, J = 4.2, 6.7 Hz, 1H), 1.75 - 1.60 (m, 1H), 1.55 (br d, J = 7.2 Hz, 3H), 1.17 (ddd, J = 2.8, 6.2, 12.3 Hz, 1H); LCMS (電灑) m/z 513.3 (M+H)+. | H |
| 431 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.37 (br s, 1H), 11.25 (s, 1H), 8.92 (s, 1H), 8.81 (d, J = 5.7 Hz, 1H), 8.22 (s, 1H), 8.19 (s, 1H), 8.10 (s, 1H), 7.66 (d, J = 9.2 Hz, 1H), 7.49 (d, J = 9.4 Hz, 1H), 5.06 - 4.89 (m, 1H), 2.24-2.15 (m, 1H), 1.78-1.62 (m, 1H), 1.26-1.17 (m, 1H), 0.30 - 0.20 (m, 2H); LCMS (電灑) m/z 453.9 (M+H)+. | H |
| 432 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.18 (s, 1H), 11.08 (s, 1H), 8.68 (s, 1H), 8.19 (s, 1H), 7.81 (s, 1H), 7.54 (d, J = 9.3 Hz, 1H), 7.30 (dd, J = 9.3, 1.6 Hz, 1H), 6.48 (d, J = 18.1 Hz, 2H), 4.93 (ddd, J = 66.4, 10.0, 6.2 Hz, 1H), 3.40 (s, 4H), 2.19-2.12 (m, 1H), 1.71-1.62 (m, 1H), 1.19-1.12 (m, 1H); LCMS (電灑) m/z 472.10 (M+H)+. | H |
| 433 |  | 1H NMR (400 MHz, DMSO-d 6) δ 1H-NMR (400 MHz, DMSO-D6) δ 13.31 (s, 1H), 11.11 (s, 1H), 8.79 (d, J = 1.6 Hz, 1H), 8.19 (s, 1H), 7.98 (d, J = 1.6 Hz, 1H), 7.94 (d, J = 4.9 Hz, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.35 (dd, J = 9.1, 1.9 Hz, 1H), 4.93 (ddd, J = 66.2, 10.2, 6.3 Hz, 1H), 4.25 (q, J = 7.1 Hz, 1H), 2.67-2.60 (m, 3H), 2.19-2.08 (m, 1H), 1.71-1.61 (m, 1H), 1.55 (d, J = 7.1 Hz, 3H), 1.24-1.10 (m, 1H); LCMS (電灑) m/z 473.10 (M+H)+. | H |
| 434 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 (s, 1H), 11.13 (s, 1H), 8.85 (s, 1H), 8.18 (s, 1H), 8.04-8.01 (m, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.3, 1.6 Hz, 1H), 5.05-4.84 (m, 1H), 4.10 (d, J = 12.6 Hz, 2H), 2.20-2.13 (m, 1H), 2.08 (d, J = 9.3 Hz, 3H), 1.67 (dtd, J = 23.3, 6.8, 3.7 Hz, 1H), 1.24-1.14 (m, 1H), LCMS (電灑) m/z 449.05 (M+H)+. | H |
| 435 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.71 (s, 1H), 11.12 (s, 1H), 8.79 (s, 1H), 8.23 (s, 1H), 8.03 (d, J = 1.1 Hz, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.36 (dd, J = 9.3, 1.6 Hz, 1H), 6.42 (s, 1H), 5.04-4.84 (m, 1H), 3.21 (s, 3H), 2.58 (d, J = 4.4 Hz, 3H), 2.20-2.13 (m, 1H), 1.70-1.63 (m, 1H), 1.19-1.13 (m, 1H) m/z 474.10 (M+H)+. | H |
| 436 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.58 (s, 1H), 11.12 (s, 1H), 8.82 (t, J = 1.4 Hz, 1H), 8.18 (d, J = 12.1 Hz, 1H), 8.01 (s, 1H), 7.58 (d, J = 9.3 Hz, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 1H), 4.64 (q, J = 7.1 Hz, 1H), 2.19-2.12 (m, 1H), 2.02-1.96 (m, 3H), 1.81-1.77 (m, 3H), 1.66 (dtd, J = 23.3, 6.9, 3.8 Hz, 1H), 1.21-1.13 (m, 1H), LCMS (電灑) m/z 463.00 (M+H)+. | H |
| 437 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.71 (s, 1H), 11.12 (s, 1H), 8.85 (d, J = 1.1 Hz, 1H), 8.21-8.16 (m, 1H), 8.03 (d, J = 1.1 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 1H), 4.54-4.43 (m, 2H), 2.68 (d, J = 13.7 Hz, 3H), 2.20-2.13 (m, 1H), 1.67 (dtd, J = 23.3, 6.9, 3.8 Hz, 1H), 1.20-1.13 (m, 1H) LCMS (電灑) m/z 465.00 (M+H)+. | H |
| 438 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.69 (s, 1H), 11.12 (s, 1H), 8.85 (t, J = 1.4 Hz, 1H), 8.18 (s, 1H), 8.04 (s, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 3H), 3.11 (s, 3H), 2.19-2.12 (m, 1H), 1.66 (dtd, J = 23.5, 6.7, 3.5 Hz, 1H), 1.22-1.13 (m, 1H), LCMS (電灑) m/z 481.00 (M+H)+. | H |
| 439 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.81 (s, 1H), 11.14 (s, 1H), 9.65 (d, J = 6.0 Hz, 1H), 8.86 (s, 1H), 8.21 (d, J = 8.8 Hz, 2H), 8.13 (s, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.39 (dd, J = 9.1, 1.4 Hz, 1H), 6.69 (d, J = 6.6 Hz, 1H), 5.05-4.84 (m, 1H), 2.21-2.14 (m, 1H), 1.73-1.62 (m, 1H), 1.22-1.14 (m, 1H), LCMS (電灑) m/z 471.00 (M+H)+. | H |
| 440 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.33 (s, 1H), 11.12 (s, 1H), 8.85 (t, J = 1.4 Hz, 1H), 8.16 (s, 1H), 7.97 (d, J = 0.8 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.39 (dd, J = 9.3, 1.6 Hz, 1H), 5.04-4.83 (m, 2H), 3.93-3.87 (m, 1H), 3.38 (d, J = 3.3 Hz, 2H), 3.24 (s, 3H), 2.16 (dt, J = 14.4, 6.7 Hz, 1H), 1.66 (dtd, J = 23.2, 6.9, 3.8 Hz, 1H), 1.24-1.13 (m, 1H), 0.95 (d, J = 6.0 Hz, 3H); LCMS (電灑) m/z 490.10 (M+H)+. | H |
| 441 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.60 (br s, 1H), 11.08 (s, 1H), 9.39 (br d, J = 6.5 Hz, 1H), 8.80 (s, 1H), 8.16 (s, 1H), 8.02 (br s, 1H), 7.57 (d, J = 9.3 Hz, 1H), 7.36 (dd, J = 1.8, 9.2 Hz, 1H), 6.28 (t, J = 53.6 Hz, 1H), 5.55 (br t, J = 6.8 Hz, 1H), 5.04 - 4.81 (m, 1H), 2.23 - 2.10 (m, 1H), 1.73 - 1.67 (m, 1H), 1.65 (d, J = 7.2 Hz, 3H), 1.17 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS (電灑) m/z 509.2 (M+H)+. | H |
| 442 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.20 (s, 1H), 12.37 (d, J = 1.3 Hz, 1H), 11.08 (s, 1H), 8.85 (s, 1H), 8.18 (s, 1H), 8.00 (s, 1H), 7.67 (d, J = 3.1 Hz, 1H), 7.58 (d, J = 9.2 Hz, 1H), 7.40 (dd, J = 1.7. 9.2 Hz, 1H), 4.93 (m, 1H), 2.48 (s, 3H), 2.16 (m, 2H), 1.67 (m, 2H), 1.17 (m, 2H); LCMS (電灑) m/z 468.1 (M+H)+. | H |
| 443 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.68 (s, 1H), 11.11 (s, 1H), 8.81 (d, J = 1.1 Hz, 1H), 8.17 (d, J = 9.3 Hz, 1H), 8.05 (d, J = 1.1 Hz, 1H), 7.59 (d, J = 9.3 Hz, 1H), 7.37 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 1H), 4.64-4.59 (m, 1H), 2.48 (s, 2H), 2.19-2.12 (m, 1H), 1.83-1.81 (m, 3H), 1.71-1.61 (m, 1H), 1.20-1.13 (m, 1H); LCMS (電灑) m/z 478.1 (M+H)+. | H |
| 444 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.54 (s, 1H), 11.12 (s, 1H), 8.84 (s, 1H), 8.18 (s, 1H), 8.04 (s, 1H), 7.60 (d, J = 9.3 Hz, 1H), 7.38 (dd, J = 9.3, 1.6 Hz, 1H), 5.15 (d, J = 7.1 Hz, 1H), 5.04-4.83 (m, 1H), 3.06 (s, 3H), 2.20-2.13 (m, 1H), 1.97-1.91 (m, 3H), 1.72-1.62 (m, 1H), 1.20-1.13 (m, 1H); LCMS (電灑) m/z 494.1 (M+H)+. | H |
| 445 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.26 (s, 1H), 11.08 (s, 1H), 8.79 (s, 1H), 8.18 (s, 1H), 8.00 (d, J = 23.6 Hz, 2H), 7.58 (d, J = 8.8 Hz, 1H), 7.35 (dd, J = 9.1, 1.9 Hz, 1H), 5.04-4.83 (m, 1H), 4.24 (q, J = 7.1 Hz, 1H), 3.11 (td, J = 12.6, 7.1 Hz, 2H), 2.20-2.13 (m, 1H), 1.70-1.63 (m, 1H), 1.54 (d, J = 7.1 Hz, 3H), 1.21-1.13 (m, 1H), 1.01 (t, J = 7.1 Hz, 3H); LCMS (電灑) m/z 487.1 (M+H)+. | H |
| 446 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.09 (s, 1H), 11.13 (s, 1H), 8.61 (d, J=7.1 Hz, 1H), 7.74 (s, 1H), 7.63 (d, J=0.9 Hz, 1H), 7.49 (d, J=8.6 Hz, 1H), 7.32 (d, J=8.6 Hz, 1H), 6.91 (s, 1H), 6.86 (dd, J=1.9, 7.0 Hz, 1H), 5.06 - 4.98 (m, 1H), 4.88-4.84 (m, 1H), 2.34 (s, 3H), 2.15 (td, J=6.9, 13.8 Hz, 1H), 1.74 - 1.61 (m, 1H), 1.21-1.13 (m, 1H); LCMS (電灑) m/z 350.1 (M+H)+. | J |
| 447 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (s, 1H), 8.63 (d, J=7.1 Hz, 1H), 7.82 (s, 1H), 7.65 (d, J=0.9 Hz, 1H), 7.45 (d, J=11.5 Hz, 1H), 6.93 (s, 1H), 6.81 (dd, J=1.8, 7.1 Hz, 1H), 6.56 (dd, J=11.8, 17.9 Hz, 1H), 5.63 (br d, J=18.0 Hz, 1H), 5.46 - 5.36 (m, 1H), 5.06 - 4.82 (m, 1H), 2.15 (td, J=7.0, 13.8 Hz, 1H), 1.73 - 1.59 (m, 1H), 1.17 (tdd, J=6.3, 9.0, 12.3 Hz, 1H)); LCMS (電灑) m/z 380.1 (M+H)+. | J |
| 448 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (s, 1H), 8.65 (d, J=7.1 Hz, 1H), 7.88 (d, J=1.0 Hz, 1H), 7.75 (d, J=1.0 Hz, 1H), 7.63 (dd, J=1.0, 8.8 Hz, 1H), 7.51 (d, J=8.8 Hz, 1H), 6.95 (s, 1H), 6.92 (dd, J=2.0, 7.1 Hz, 1H), 5.05-4.83 (m, 1H), 2.15 (td, J=7.0, 13.8 Hz, 1H), 1.74-1.60 (m, 1H), 1.17 (tdd, J=6.3, 9.0, 12.3 Hz, 1H); LCMS (電灑) m/z 370.1 (M+H)+. | J |
| 449 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.10 (s, 1H), 8.56 (br d, J=7.0 Hz, 1H), 7.90 (s, 1H), 7.74 (s, 1H), 7.58 (br d, J=9.2 Hz, 1H), 7.35 (d, J=8.9 Hz, 1H), 6.98 (br d, J=7.1 Hz, 1H), 6.89 (s, 1H), 5.08-4.80 (m, 1H), 3.80 (s, 3H), 2.19-2.08 (m, 1H), 1.75-1.60 (m, 1H), 1.26-1.07 (m, 1H); LCMS (電灑) m/z 366.1 (M+H)+. | J |
| 450 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.18 (br s, 1H), 8.68 (br s, 1H), 8.12-7.54 (m, 5H), 7.04-6.85 (m, 2H), 5.05-4.84 (m, 1H), 3.10 (br s, 6H), 2.16 (td, J=7.0, 14.0 Hz, 1H), 1.73-1.62 (m, 1H), 1.23-1.14 (m, 1H); LCMS (電灑) m/z 379.1 (M+H)+. | J |
| 451 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.19-13.15 (m, 1H), 11.17 (s, 1H), 8.64 (d, J=7.1 Hz, 1H), 7.87 (s, 1H), 7.82-7.74 (m, 2H), 7.64 (s, 1H), 6.93 (s, 1H), 6.83 (dd, J=1.8, 7.1 Hz, 1H), 5.08-4.81 (m, 1H), 2.20-2.10 (m, 1H), 1.74-1.59 (m, 1H), 1.17 (tdd, J=6.2, 9.0, 12.4 Hz, 1H); LCMS (電灑) m/z 404.1 (M+H)+. | J |
| 452 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.10 (br s, 1H), 11.13 (s, 1H), 8.61 (d, J=7.1 Hz, 1H), 7.68 (s, 1H), 7.59 (d, J=1.0 Hz, 1H), 7.53 (d, J=8.6 Hz, 1H), 7.36 (d, J=8.7 Hz, 1H), 6.90 (s, 1H), 6.81 (dd, J=1.9, 7.0 Hz, 1H), 5.06 - 4.81 (m, 1H), 2.70 - 2.59 (m, 2H), 2.20 - 2.10 (m, 1H), 1.75 - 1.58 (m, 1H), 1.18 (td, J=3.1, 6.1 Hz, 1H), 1.12 (t, J=7.5 Hz, 3H); LCMS (電灑) m/z 364.2 (M+H)+. | J |
| 453 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (s, 1H), 8.61 (d, J=7.1 Hz, 1H), 7.97 (d, J=0.7 Hz, 1H), 7.77 (d, J=8.8 Hz, 1H), 7.69 - 7.64 (m, 1H), 7.61 (d, J=1.1 Hz, 1H), 6.92 (s, 1H), 6.82 (dd, J=2.0, 7.1 Hz, 1H), 5.06 - 4.82 (m, 1H), 2.33 (s, 3H), 2.21 - 2.11 (m, 1H), 1.73 - 1.61 (m, 1H), 1.18 (tdd, J=6.1, 8.9, 12.3 Hz, 1H); LCMS (電灑) m/z 378.2 (M+H)+. | J |
| 454 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.11 (s, 1H), 8.58 (d, J=7.1 Hz, 1H), 7.82 (s, 1H), 7.66 (s, 1H), 7.40 (d, J=12.0 Hz, 1H), 6.93 - 6.87 (m, 2H), 5.05 - 4.82 (m, 1H), 2.67 (s, 6H), 2.19 - 2.09 (m, 1H), 1.73 - 1.61 (m, 1H), 1.22 - 1.12 (m, 1H); LCMS (電灑) m/z =397.1 (M+H+) | J |
| 455 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.43 (br s, 1H), 11.15 (s, 1H), 8.65 (d, J=7.1 Hz, 1H), 7.83 (s, 1H), 7.70 (dd, J=0.8, 1.8 Hz, 1H), 7.67-7.63 (m, 1H), 7.58-7.55 (m, 1H), 6.95 (s, 1H), 6.88 (dd, J=1.9, 7.2 Hz, 1H), 5.05-4.83 (m, 1H), 2.20-2.10 (m, 1H), 1.72-1.61 (m, 1H), 1.18 (qd, J=6.2, 15.1 Hz, 1H); LCMS (電灑) m/z =414.0 (M+H+) | J |
| 456 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.21 (s, 1H), 8.73 (d, J=7.2 Hz, 1H), 8.19 (s, 1H), 7.94 (d, J=1.2 Hz, 1H), 7.85-7.73 (m, 2H), 7.09 (dd, J=2.0, 7.1 Hz, 1H), 7.02 (s, 1H), 5.08-4.82 (m, 1H), 2.16 (td, J=7.0, 13.8 Hz, 1H), 1.74-1.62 (m, 1H), 1.18 (tdd, J=6.3, 9.1, 12.3 Hz, 1H); LCMS (電灑): m/z =361.1 (M+H+) | J |
| 457 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.14 (s, 1H), 8.62 (d, J=7.1 Hz, 1H), 7.83 (s, 1H), 7.74 (d, J=0.9 Hz, 1H), 7.34 (d, J=10.5 Hz, 1H), 6.98 (dd, J=1.8, 7.1 Hz, 1H), 6.92 (s, 1H), 5.06 - 4.99 (m, 1H), 4.90 - 4.82 (m, 1H), 2.15 (td, J=7.0, 13.6 Hz, 1H), 2.01 - 1.93 (m, 1H), 1.74 - 1.61 (m, 1H), 1.22-1.13 (m, 1H), 0.77 - 0.69 (m, 2H), 0.33 - 0.25 (m, 2H); LCMS (電灑) m/z =394.1 (M+H+) | J |
| 458 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.50 (br s, 1H), 11.17 (s, 1H), 8.68 (d, J=7.2 Hz, 1H), 7.92 (s, 1H), 7.79 (d, J=1.0 Hz, 1H), 7.68 (dd, J=0.9, 9.0 Hz, 1H), 6.97 (s, 1H), 6.96 (d, J=2.0 Hz, 1H), 6.96 - 6.93 (m, 1H), 5.06 - 5.00 (m, 1H), 4.88-4.84 (m, 1H), 2.18-2.12 (m, 1H), 1.75 - 1.59 (m, 1H), 1.22-1.14 (tdd, J=6.2, 9.2, 12.4 Hz, 1H); LCMS (電灑)m/z =388.0 (M+H+) | J |
| 459 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.10 (s, 1H), 11.15 (s, 1H), 8.62 (d, J=7.1 Hz, 1H), 7.75 - 7.67 (m, 2H), 7.48 (d, J=8.8 Hz, 1H), 7.02 (d, J=8.8 Hz, 1H), 6.96 - 6.88 (m, 2H), 5.07 - 4.82 (m, 1H), 2.20 - 2.08 (m, 1H), 2.03 - 1.94 (m, 1H), 1.74 - 1.60 (m, 1H), 1.22 - 1.11 (m, 1H), 0.90 - 0.78 (m, 2H), 0.70 - 0.60 (m, 2H); LCMS (電灑) m/z =376.1 (M+H+) | J |
| 460 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.17 (br s, 1H), 11.15 (s, 1H), 8.64 (d, J=7.1 Hz, 1H), 7.77 (s, 1H), 7.67 (d, J=0.9 Hz, 1H), 7.38 (d, J=9.9 Hz, 1H), 6.93 (s, 1H), 6.87 (dd, J=2.0, 7.1 Hz, 1H), 5.06 - 4.81 (m, 1H), 2.23 (d, J=2.6 Hz, 3H), 2.15 (td, J=6.9, 13.8 Hz, 1H), 1.75 - 1.59 (m, 1H), 1.17 (tdd, J=6.3, 9.1, 12.3 Hz, 1H); LCMS (電灑) m/z =368.1 (M+H+) | J |
| 461 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.18 (br s, 1H), 11.14 (s, 1H), 8.62 (d, J=7.1 Hz, 1H), 7.82 (s, 1H), 7.69 (s, 1H), 7.58 (s, 2H), 6.94 (dd, J=1.9, 7.0 Hz, 1H), 6.91 (s, 1H), 5.09 - 4.80 (m, 1H), 4.50 (s, 2H), 2.22 - 2.09 (m, 1H), 1.75 - 1.58 (m, 1H), 1.24 - 1.11 (m, 1H); LCMS (電灑) m/z =366.0 (M+H+) | J |
| 462 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.14 (s, 1H), 8.63 (d, J=7.0 Hz, 1H), 7.64 (d, J=3.1 Hz, 1H), 7.59 (d, J=0.8 Hz, 1H), 7.36 (d, J=12.3 Hz, 1H), 6.92 (s, 1H), 6.78 (dd, J=1.8, 7.1 Hz, 1H), 5.07 - 4.97 (m, 1H), 4.88-4.84 (m, 1H), 3.13 - 3.00 (m, 1H), 2.18-2.11 (m, 1H), 1.74 - 1.60 (m, 1H), 1.28 (dd, J=7.1, 11.6 Hz, 6H), 1.21 - 1.08 (m, 1H); LCMS (電灑) m/z =396.1 (M+H+) | J |
| 463 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.25 (br s, 1H), 11.33-10.98 (m, 1H), 11.13 (s, 1H), 8.61 (d, J=7.0 Hz, 1H), 7.76 (s, 1H), 7.66-7.59 (m, 2H), 7.56-7.51 (m, 1H), 6.92 (s, 1H), 6.87 (dd, J=1.8, 7.1 Hz, 1H), 5.23-4.71 (m, 1H), 2.39 (s, 3H), 2.20-2.10 (m, 1H), 1.75-1.58 (m, 1H), 1.17 (tdd, J=6.2, 9.1, 12.2 Hz, 1H); LCMS (電灑) m/z =382.1 (M+H+) | J |
| 464 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.48 (br s, 1H), 11.17 (s, 1H), 8.67 (d, J=7.1 Hz, 1H), 7.86 (s, 1H), 7.74 (d, J=1.0 Hz, 1H), 7.66 - 7.61 (m, 1H), 6.96 (s, 1H), 6.90 (dd, J=2.0, 7.1 Hz, 1H), 5.08 - 4.80 (m, 1H), 2.14 (br d, J=7.2 Hz, 1H), 1.75 - 1.60 (m, 1H), 1.21 - 1.14 (m, 1H); LCMS (電灑) m/z =432.0 (M+H+) | J |
| 465 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.52 (br s, 1H), 11.17 (s, 1H), 8.67 (d, J=7.0 Hz, 1H), 7.94 (s, 1H), 7.78 - 7.74 (m, 1H), 7.73 - 7.69 (m, 1H), 7.66 (s, 1H), 7.11 - 6.80 (m, 3H), 5.07 - 4.83 (m, 1H), 2.19 - 2.10 (m, 1H), 1.74 - 1.62 (m, 1H), 1.18 (tdd, J=6.4, 9.0, 12.3 Hz, 1H); LCMS (電灑) m/z =386.2 (M+H+) | J |
| 466 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.15 (s, 1H), 8.64 (d, J=7.1 Hz, 1H), 7.70 (s, 1H), 7.63 (s, 1H), 7.39 (d, J=10.4 Hz, 1H), 6.93 (s, 1H), 6.82 (dd, J=1.8, 7.0 Hz, 1H), 5.06 - 4.81 (m, 1H), 2.66 - 2.57 (m, 2H), 2.20 - 2.09 (m, 1H), 1.74 - 1.60 (m, 1H), 1.22 - 1.14 (m, 1H), 1.10 (t, J=7.4 Hz, 3H); LCMS (電灑) m/z =382.1 (M+H+) | J |
| 467 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.27 (s, 1H), 11.15 (s, 1H), 8.67 - 8.61 (m, 1H), 7.97 (s, 1H), 7.84 - 7.80 (m, 1H), 7.56 - 7.48 (m, 1H), 7.05 - 6.99 (m, 1H), 6.95 (s, 1H), 5.08 - 4.82 (m, 1H), 3.67 (s, 2H), 3.71 - 3.63 (m, 1H), 2.07 (s, 1H), 1.75 - 1.61 (m, 1H), 1.26 - 1.09 (m, 1H); LCMS (電灑) m/z =384.1 (M+H+) | J |
| 468 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.60 (br s, 1H), 11.21 (s, 1H), 8.68 (d, J=7.1 Hz, 1H), 7.93 (s, 1H), 7.69 (s, 1H), 7.60 (d, J=11.2 Hz, 1H), 7.09 - 6.79 (m, 3H), 5.08 - 4.81 (m, 1H), 2.19 - 2.11 (m, 1H), 1.73 - 1.61 (m, 1H), 1.23 - 1.14 (m, 1H); LCMS (電灑) m/z =404.1 (M+H+) | J |
| 469 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.40 (s, 1H), 11.14 (br d, J=3.1 Hz, 1H), 8.62 (d, J=7.0 Hz, 1H), 7.52 (s, 1H), 7.44 (d, J=9.8 Hz, 1H), 6.90 (s, 1H), 6.74 (dd, J=1.8, 7.1 Hz, 1H), 5.09 - 4.79 (m, 1H), 2.19 - 2.12 (m, 1H), 2.09 (t, J=2.4 Hz, 3H), 1.75 - 1.60 (m, 1H), 1.23 - 1.09 (m, 1H); LCMS (電灑) m/z =402.0 (M+H+) | J |
| 470 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (d, J=3.5 Hz, 1H), 8.63 (d, J=7.0 Hz, 1H), 7.53 (d, J=0.7 Hz, 1H), 7.29 (d, J=10.0 Hz, 1H), 6.91 (s, 1H), 6.75 (dd, J=1.8, 7.0 Hz, 1H), 5.11 - 4.79 (m, 1H), 2.15 (td, J=6.8, 13.4 Hz, 1H), 2.07 (t, J=2.4 Hz, 3H), 1.90 (d, J=4.3 Hz, 3H), 1.74 - 1.59 (m, 1H), 1.24 - 1.10 (m, 1H); LCMS (電灑) m/z 382.0 (M+H)+. | J |
| 471 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.37 (s, 1H), 11.15 (s, 1H), 8.59 (d, J=7.1 Hz, 1H), 7.60 (d, J=1.0 Hz, 1H), 6.95 (d, J=10.1 Hz, 1H), 6.91 (s, 1H), 6.88 (dd, J=2.0, 7.1 Hz, 1H), 5.11 - 4.77 (m, 1H), 2.43 (s, 6H), 2.14 (td, J=6.9, 13.9 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.24 - 1.11 (m, 1H); LCMS (電灑) m/z 414.4 (M+H)+. | J |
| 472 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.53 (s, 1H), 11.15 (br d, J=5.6 Hz, 1H), 8.59 (d, J=7.0 Hz, 1H), 7.52 (s, 1H), 7.45 (d, J=9.7 Hz, 1H), 6.90 (s, 1H), 6.75 (dd, J=1.7, 7.0 Hz, 1H), 5.09 - 4.80 (m, 1H), 3.79 (d, J=2.9 Hz, 1H), 2.20 - 2.14 (m, 1H), 2.12 (br d, J=1.7 Hz, 3H), 1.74 - 1.59 (m, 1H), 1.27 - 1.08 (m, 1H); LCMS (電灑) m/z 392.2 (M+H+) | J |
| 473 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.49 (d, J=7.2 Hz, 1H), 7.51 (s, 1H), 7.17 (d, J=9.7 Hz, 1H), 6.80 (br d, J=5.4 Hz, 1H), 4.98 - 4.76 (m, 1H), 2.15 (s, 3H), 2.12 - 2.03 (m, 1H), 1.87 - 1.73 (m, 1H), 1.40 - 1.30 (m, 1H), 1.27 - 1.15 (m, 1H), 0.83 - 0.74 (m, 1H), 0.69 (br s, 1H), 0.55 - 0.40 (m, 2H); LCMS (電灑) m/z 408.4 (M+H+) | J |
| 474 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.17 (d, J=4.4 Hz, 1H), 8.67 (d, J=7.1 Hz, 1H), 7.53 (s, 1H), 7.37 (d, J=9.8 Hz, 1H), 6.91 (s, 1H), 6.73 (dd, J=1.8, 7.1 Hz, 1H), 6.04 - 5.92 (m, 1H), 5.85 - 5.75 (m, 1H), 5.06 - 4.82 (m, 2H), 2.15 (br d, J=6.5 Hz, 1H), 2.07 (t, J=2.4 Hz, 3H), 1.74 - 1.60 (m, 1H), 1.24 - 1.11 (m, 1H); LCMS (電灑) m/z 394.3 (M+H+) | J |
| 475 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (br d, J=4.8 Hz, 1H), 8.63 (d, J=7.1 Hz, 1H), 7.55 (s, 1H), 7.29 (d, J=9.9 Hz, 1H), 6.90 (s, 1H), 6.76 (dd, J=1.8, 7.0 Hz, 1H), 5.07 - 4.81 (m, 1H), 2.31 - 2.24 (m, 2H), 2.14 (br d, J=6.7 Hz, 1H), 2.06 (t, J=2.4 Hz, 3H), 1.75 - 1.59 (m, 1H), 1.24 - 1.09 (m, 1H), 0.90 (dt, J=4.0, 7.5 Hz, 3H); LCMS (電灑) m/z 396.3 (M+H+) | J |
| 476 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.12 (br d, J = 0.7 Hz, 1H), 11.18 (s, 1H), 8.69 (d, J = 7.2 Hz, 1H), 8.04 (br s, 1H), 7.80 (s, 1H), 6.98 (s, 1H), 6.95 (dd, J = 1.8, 7.1 Hz, 1H), 5.05 - 4.84 (m, 1H), 2.18 - 2.11 (m, 1H), 1.73 - 1.62 (m, 1H), 1.23 - 1.15 (m, 1H); LCMS (電灑) m/z 422.1 (M+H)+. | J |
| 477 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.31 (br s, 1H), 11.14 (s, 1H), 8.63 (d, J=7.1 Hz, 1H), 7.77 (s, 1H), 7.63 (d, J=1.0 Hz, 1H), 6.92 (s, 1H), 6.84 (dd, J=1.8, 7.1 Hz, 1H), 5.11 - 4.75 (m, 1H), 2.47 (d, J=1.6 Hz, 3H), 2.22 (d, J=2.9 Hz, 3H), 2.15 (td, J=6.8, 13.8 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.17 (tdd, J=6.3, 9.1, 12.4 Hz, 1H); LCMS (電灑) m/z 382.4 (M+H)+. | J |
| 478 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.16 - 12.54 (m, 1H), 11.20 (s, 1H), 8.71 (d, J=7.2 Hz, 1H), 8.00 (s, 1H), 7.82 (s, 1H), 7.00 (s, 1H), 6.96 (dd, J=1.8, 7.2 Hz, 1H), 5.11 - 4.79 (m, 1H), 2.15 (td, J=6.9, 13.8 Hz, 1H), 1.96 (s, 3H), 1.92 (s, 3H), 1.76 - 1.60 (m, 1H), 1.18 (tdd, J=6.4, 9.1, 12.2 Hz, 1H); LCMS (電灑) m/z 464.1 (M+H)+. | J |
| 479 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.80 (br s, 1H), 11.17 (s, 1H), 8.66 (d, J=7.1 Hz, 1H), 7.90 (br s, 1H), 7.69 (s, 1H), 6.94 (s, 1H), 6.87 (dd, J=2.0, 7.1 Hz, 1H), 5.10 - 4.78 (m, 1H), 2.27 (d, J=2.8 Hz, 3H), 2.19 - 2.07 (m, 1H), 1.74 - 1.60 (m, 1H), 1.24 - 1.11 (m, 1H); LCMS (電灑) m/z 402.0 (M+H)+. | J |
| 480 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.00 (br s, 1H), 11.18 (s, 1H), 8.68 (d, J=7.2 Hz, 1H), 8.08 (br s, 1H), 7.80 (d, J=0.8 Hz, 1H), 6.98 (s, 1H), 6.95 (dd, J=1.9, 7.2 Hz, 1H), 5.08 - 4.79 (m, 1H), 2.15 (td, J=7.0, 13.6 Hz, 1H), 1.75 - 1.60 (m, 1H), 1.26 - 1.09 (m, 1H); LCMS (電灑) m/z 466.3 (M+H)+. | J |
| 481 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.54 (d, J=7.1 Hz, 1H), 7.85 (d, J=3.2 Hz, 1H), 7.59 (s, 1H), 6.98 (s, 1H), 6.86 (dd, J=1.9, 7.2 Hz, 1H), 5.00 - 4.96 (m, 1H), 2.34 (d, J=3.2 Hz, 3H),2.20 - 2.16 (m, 1H), 1.92 - 1.72 (m, 1H), 1.30 - 1.15 (m, 1H); LCMS (電灑) m/z 386.0 (M+H)+. | J |
| 482 |  | 1H NMR (400MHz, METHANOL-d 4) δ 8.55 (d, J = 7.1 Hz, 1H), 7.89 (s, 1H), 7.63 (s, 1H), 7.00 (s, 1H), 6.87 (dd, J = 1.7, 7.1 Hz, 1H), 4.99 - 4.91 (m, 1H), 2.31 (d, J = 3.1 Hz, 3H), 2.14 - 2.04 (m, 1H), 1.87 - 1.75 (m, 1H), 1.27 - 1.16 (m, 1H); LCMS (電灑) m/z 435.9 (M+H)+. | J |
| 483 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.36 (br s, 1H), 11.16 (s, 1H), 8.63 (d, J=7.1 Hz, 1H), 7.81 (s, 1H), 7.65 (s, 1H), 7.52 (s, 1H), 7.15 (dd, J=11.1, 18.0 Hz, 1H), 6.92 (s, 1H), 6.87 (dd, J=1.8, 7.1 Hz, 1H), 6.11 (br d, J=17.6 Hz, 1H), 5.51 (d, J=11.6 Hz, 1H), 5.05 - 4.85 (m, 1H), 2.36 (s, 3H), 2.14 (br d, J=8.1 Hz, 1H), 1.72 - 1.64 (m, 1H), 1.21 - 1.15 (m, 1H); LCMS (電灑) m/z 376.1 (M+H)+. | J |
| 484 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.51 (br s, 1H), 11.16 (s, 1H), 8.64 (d, J=7.1 Hz, 1H), 7.87 (s, 1H), 7.73 (d, J=1.0 Hz, 1H), 6.95 (s, 1H), 6.91 (dd, J=1.9, 7.2 Hz, 1H), 5.10 - 4.78 (m, 1H), 3.00 (br s, 6H), 2.15 (td, J=7.0, 13.8 Hz, 1H), 1.74 - 1.61 (m, 1H), 1.24 - 1.11 (m, 1H); LCMS (電灑) m/z 431.1 (M+H)+. | J |
| 485 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.79 (s, 1H), 11.17 (s, 1H), 8.68 (d, J=7.1 Hz, 1H), 7.98 (s, 1H), 7.79 (d, J=1.0 Hz, 1H), 6.98 (s, 1H), 6.94 (dd, J=2.0, 7.1 Hz, 1H), 5.08 - 4.77 (m, 1H), 2.57 (s, 3H), 2.15 (td, J=6.9, 13.9 Hz, 1H), 1.74 - 1.61 (m, 1H), 1.18 (tdd, J=6.3, 9.1, 12.3 Hz, 1H); LCMS (電灑) m/z 434.2 (M+H)+. | J |
| 486 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.51 (br s, 1H), 11.20 (s, 1H), 8.72 (d, J=7.2 Hz, 1H), 8.10 (s, 1H), 7.84 (d, J=1.0 Hz, 1H), 7.02 (s, 1H), 6.96 (dd, J=1.9, 7.2 Hz, 1H), 5.07 - 4.77 (m, 1H), 3.56 (s, 3H), 2.15 (quin, J=6.9 Hz, 1H), 1.75 - 1.58 (m, 1H), 1.18 (tdd, J=6.3, 9.0, 12.3 Hz, 1H); LCMS (電灑) m/z 466.1 (M+H)+. | J |
| 487 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.69 (br s, 1H), 11.19 (s, 1H), 8.66 (d, J=7.0 Hz, 1H), 7.92 (br s, 1H), 7.69 (d, J=1.0 Hz, 1H), 6.94 (s, 1H), 6.87 (dd, J=1.9, 7.1 Hz, 1H), 5.07 - 4.82 (m, 1H), 2.27 (d, J=3.0 Hz, 3H), 2.20 - 2.10 (m, 1H), 1.74 - 1.60 (m, 1H), 1.18 (tdd, J=6.2, 9.1, 12.3 Hz, 1H); LCMS (電灑) m/z 448.1 (M+H)+. | J |
| 488 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (s, 1H), 11.18 (s, 1H), 8.65 (d, J = 7.0 Hz, 1H), 7.84 (s, 1H), 7.68 (s, 1H), 6.93 (s, 1H), 6.87 (dd, J = 1.9, 7.1 Hz, 1H), 5.05 - 4.84 (m, 1H), 2.52 (br s, 3H), 2.24 (d, J = 2.9 Hz, 3H), 2.19 - 2.10 (m, 1H), 1.73 - 1.61 (m, 1H), 1.22 - 1.13 (m, 1H); LCMS (電灑) m/z 414.2 (M+H)+. | J |
| 489 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.23 (s, 1H), 11.21 (s, 1H), 8.70 (d, J = 7.2 Hz, 1H), 7.95 (s, 1H), 7.74 (d, J = 0.9 Hz, 1H), 6.97 (s, 1H), 6.90 (dd, J = 1.9, 7.2 Hz, 1H), 5.05 - 4.84 (m, 1H), 3.50 (s, 3H), 2.27 (d, J = 2.8 Hz, 3H), 2.15 (td, J = 6.9, 13.9 Hz, 1H), 1.73 - 1.62 (m, 1H), 1.25 - 1.12 (m, 1H); LCMS (電灑) m/z 446.2 (M+H)+. | J |
| 490 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.14 (s, 1H), 8.62 (d, J = 7.2 Hz, 1H), 7.75 (s, 1H), 7.61 (d, J = 1.0 Hz, 1H), 6.90 (s, 1H), 6.84 (dd, J = 1.9, 7.1 Hz, 1H), 5.05 - 5.00 (m, 1H), 4.88 - 4.83 (m, 1H), 2.96 (d, J = 2.0 Hz, 6H), 2.20 (d, J = 3.4 Hz, 3H), 2.17 - 2.09 (m, 1H), 1.73 - 1.61 (m, 1H), 1.21 - 1.12 (m, 1H); LCMS (電灑) m/z 411.2 (M+H)+. | J |
| 491 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (br s, 1H), 11.14 (s, 1H), 8.62 (d, J=7.0 Hz, 1H), 7.79 (br s, 1H), 7.62 (d, J=1.0 Hz, 1H), 6.91 (s, 1H), 6.84 (dd, J=1.9, 7.1 Hz, 1H), 5.08 - 4.80 (m, 1H), 4.08 (s, 3H), 2.23 (d, J=3.1 Hz, 3H), 2.15 (td, J=6.9, 14.0 Hz, 1H), 1.75 - 1.59 (m, 1H), 1.24 - 1.11 (m, 1H); LCMS (電灑) m/z 398.2 (M+H)+. | J |
| 492 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.84 (br s, 1H), 11.16 (s, 1H), 8.66 (d, J=7.2 Hz, 1H), 7.94 (s, 1H), 7.77 - 7.72 (m, 1H), 6.96 (s, 1H), 6.91 (dd, J=1.9, 7.1 Hz, 1H), 5.09 - 4.77 (m, 1H), 4.16 (d, J=1.5 Hz, 3H), 2.15 (td, J=6.9, 13.7 Hz, 1H), 1.74 - 1.59 (m, 1H), 1.24 - 1.10 (m, 1H); LCMS (電灑) m/z 418.2 (M+H)+. | J |
| 493 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.80 (br s, 1H), 11.17 (s, 1H), 8.66 (d, J=7.1 Hz, 1H), 7.94 (br s, 1H), 7.75 (s, 1H), 6.95 (s, 1H), 6.92 (dd, J=1.8, 7.2 Hz, 1H), 5.13 - 4.78 (m, 1H), 4.39 (br d, J=6.5 Hz, 2H), 2.21 - 2.09 (m, 1H), 1.74 - 1.60 (m, 1H), 1.41 (t, J=7.0 Hz, 3H), 1.24 - 1.12 (m, 1H); LCMS (電灑) m/z 432.4 (M+H)+. | J |
| 494 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.14 (s, 1H), 8.60 (d, J=7.1 Hz, 1H), 7.88 (s, 1H), 7.68 (dd, J=0.8, 1.8 Hz, 1H), 6.92 (s, 1H), 6.89 (dd, J=2.0, 7.1 Hz, 1H), 5.08 - 4.78 (m, 1H), 3.17 (d, J=2.8 Hz, 3H), 2.14 (td, J=7.0, 13.9 Hz, 1H), 1.74 - 1.58 (m, 1H), 1.17 (tdd, J=6.3, 9.0, 12.3 Hz, 1H); LCMS (電灑) m/z 417.4 (M+H)+. | J |
| 495 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (br d, J = 2.8 Hz, 1H), 11.18 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 8.17 (s, 1H), 7.90 (br s, 1H), 7.77 - 7.68 (m, 1H), 6.95 (s, 1H), 6.91 (dd, J = 2.0, 7.1 Hz, 1H), 5.06 - 4.83 (m, 1H), 3.30 (br s, 4H), 2.57 (br s, 4H), 2.28 (s, 3H), 2.19 - 2.10 (m, 1H), 1.73 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS (電灑) m/z 486.2 (M+H)+. | J |
| 496 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (1 H, s) 8.62 (1 H, d, J=7.20 Hz) 7.89 (1 H, br s) 7.70 (1 H, d, J=1.00 Hz) 7.04 – 6.79 (2 H, m) 5.07 – 4.70 (1 H, m) 2.15 (1 H, dt, J=13.85, 7.02 Hz) 1.73 - 1.61 (1 H, m) 1.25 - 1.16 (4 H, m); LCMS (電灑) m/z 431.0 (M+H)+. | J |
| 497 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.78 - 13.23 (1 H, m) 11.18 (1 H, s) 8.66 (1 H, d, J=7.20 Hz) 7.90 (1 H, s) 7.83 - 7.73 (1 H, m) 7.05 – 6.90 (2 H, m) 5.10 – 4.83 (1 H, m) 3.30 (4 H, q, J=6.65 Hz) 2.15 (1 H, dt, J=13.77, 6.98 Hz) 1.77 - 1.61 (1 H, m) 1.27 - 1.14 (1 H, m) 1.02 (6 H, t, J=7.09 Hz); LCMS (電灑) m/z 459.0 (M+H)+. | J |
| 498 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.53 (br s, 1H), 11.16 (s, 1H), 8.65 (d, J = 7.2 Hz, 1H), 7.90 (br s, 1H), 7.74 (d, J = 1.0 Hz, 1H), 6.95 (s, 1H), 6.93 - 6.88 (m, 1H), 5.05 - 4.83 (m, 1H), 3.92 - 3.76 (m, 4H), 3.30 - 3.21 (m, 4H), 2.14 (td, J = 6.9, 13.9 Hz, 1H), 1.73 - 1.61 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS (電灑) m/z 473.3 (M+H)+. | J |
| 499 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.24 (br s, 1H), 11.14 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.89 (br s, 1H), 7.69 (d, J = 1.0 Hz, 1H), 6.92 (s, 1H), 6.88 (dd, J = 2.0, 7.1 Hz, 1H), 5.07 - 4.82 (m, 1H), 3.72 (br s, 4H), 2.19 - 2.10 (m, 1H), 1.99 - 1.90 (m, 4H), 1.74 - 1.61 (m, 1H), 1.23 - 1.12 (m, 1H); LCMS (電灑) m/z 457.3 (M+H)+. | J |
| 500 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.61 (br s, 1H), 11.17 (s, 1H), 8.81 (br s, 2H), 8.67 (d, J = 7.1 Hz, 1H), 7.94 (br s, 1H), 7.73 (d, J = 1.0 Hz, 1H), 6.97 (s, 1H), 6.90 (dd, J = 1.9, 7.2 Hz, 1H), 5.08 - 4.81 (m, 1H), 3.62 - 3.40 (m, 8H), 2.22 - 2.09 (m, 1H), 1.74 - 1.59 (m, 1H), 1.26 - 1.11 (m, 1H); LCMS (電灑) m/z 472.3 (M+H)+. | J |
| 501 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.10 (br s, 1H), 11.14 (s, 1H), 8.61 (d, J=7.1 Hz, 1H), 7.88 (br s, 1H), 7.68 (d, J=0.9 Hz, 1H), 6.92 (s, 1H), 6.88 (dd, J=1.9, 7.1 Hz, 1H), 5.16 - 4.74 (m, 1H), 4.51 - 4.25 (m, 4H), 2.35 (quin, J=7.3 Hz, 2H), 2.14 (td, J=6.9, 13.9 Hz, 1H), 1.76 - 1.57 (m, 1H), 1.29 - 1.06 (m, 1H); LCMS (電灑) m/z 443.3 (M+H)+. | J |
| 502 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.45 (br s, 1H), 11.17 (s, 1H), 9.37 (br s, 1H), 8.66 (d, J=7.1 Hz, 1H), 7.90 (br s, 1H), 7.74 (d, J=1.0 Hz, 1H), 6.96 (s, 1H), 6.92 (dd, J=2.0, 7.1 Hz, 1H), 5.05 - 4.84 (m, 1H), 3.13 (br s, 2H), 2.92 (d, J=2.4 Hz, 3H), 2.72 (s, 3H), 2.70 (s, 3H), 2.14 (br d, J=7.1 Hz, 1H), 2.02 (br s, 4H), 1.73 - 1.62 (m, 1H), 1.48 (br s, 4H), 1.23 - 1.13 (m, 1H); LCMS(電灑) m/z542.3 (M +H+). | J |
| 503 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.94 - 13.16 (m, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.90 (s, 1H), 7.82 - 7.71 (m, 1H), 7.84 - 7.70 (m, 1H), 7.04 - 6.85 (m, 2H), 5.09 - 4.82 (m, 1H), 3.44 - 3.32 (m, 1H), 3.24 - 3.06 (m, 1H), 2.95 - 2.81 (m, 3H), 2.23 - 2.07 (m, 1H), 1.90 - 1.76 (m, 3H), 1.74 - 1.34 (m, 6H), 1.26 - 1.07 (m, 3H); LCMS(電灑) m/z 515.2 (M +H+). | J |
| 504 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (br s, 1H), 11.17 (s, 1H), 8.66 (d, J=7.1 Hz, 1H), 8.37 (br s, 2H), 7.91 (s, 1H), 7.74 (d, J=1.0 Hz, 1H), 6.96 (s, 1H), 6.92 (dd, J=2.0, 7.2 Hz, 1H), 5.07 - 4.82 (m, 1H), 3.10 (br s, 1H), 2.91 (d, J=2.6 Hz, 3H), 2.56 - 2.52 (m, 5H), 2.15 (td, J=6.9, 13.5 Hz, 1H), 2.06 (br d, J=9.9 Hz, 2H), 1.99 (br d, J=11.5 Hz, 2H), 1.72 - 1.61 (m, 1H), 1.54 - 1.44 (m, 2H), 1.38 - 1.26 (m, 2H), 1.21 - 1.14 (m, 1H); LCMS(電灑) m/z 528.3 (M +H+). | J |
| 505 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.35 (br s, 1H), 11.18 (s, 1H), 8.67 (d, J=7.2 Hz, 1H), 8.33 (br s, 2H), 7.94 (s, 1H), 7.79 - 7.75 (m, 1H), 6.97 (s, 1H), 6.94 (dd, J=2.0, 7.1 Hz, 1H), 5.06 - 4.84 (m, 1H), 3.08 (br s, 1H), 2.85 (s, 3H), 2.57 (t, J=5.4 Hz, 3H), 2.54 - 2.52 (m, 2H), 2.15 (td, J=7.2, 14.0 Hz, 1H), 1.83 (br s, 4H), 1.72 - 1.56 (m, 5H), 1.23 - 1.13 (m, 1H); LCMS(電灑) m/z 528.3 (M +H+). | J |
| 506 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.33 (br s, 1H), 11.11 (s, 1H), 8.58 (d, J = 7.0 Hz, 1H), 7.71 (s, 1H), 7.57 (d, J = 0.9 Hz, 1H), 6.88 (s, 1H), 6.84 - 6.79 (m, 2H), 5.07 - 4.80 (m, 1H), 3.99 (s, 3H), 2.35 (s, 3H), 2.14 (td, J = 7.1, 14.0 Hz, 1H), 1.73 - 1.61 (m, 1H), 1.17 (tdd, J = 6.2, 8.9, 12.3 Hz, 1H); LCMS(電灑) m/z 380.2 (M+H+). | J |
| 507 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.76 (br s, 1H), 11.18 (s, 1H), 8.66 (d, J=7.1 Hz, 1H), 7.94 (br s, 1H), 7.75 (d, J=1.0 Hz, 1H), 6.95 (s, 1H), 6.92 (dd, J=2.0, 7.1 Hz, 1H), 5.06 - 4.83 (m, 1H), 4.33 (br s, 2H), 4.27 - 4.20 (m, 1H), 3.81 - 3.74 (m, 1H), 3.69 (dt, J=6.1, 7.6 Hz, 1H), 2.18 - 2.10 (m, 1H), 2.07 - 1.98 (m, 1H), 1.92 - 1.81 (m, 2H), 1.80 - 1.73 (m, 1H), 1.72 - 1.62 (m, 1H), 1.18 (tdd, J=6.2, 9.1, 12.3 Hz, 1H); LCMS(電灑) m/z 488.2 (M +H+). | J |
| 508 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.30 (br s, 1H), 11.16 (s, 1H), 8.62 (br d, J=7.1 Hz, 1H), 8.45 (br s, 2H), 7.85 (s, 1H), 7.70 (s, 1H), 6.93 (s, 1H), 6.89 (dd, J=2.0, 7.1 Hz, 1H), 5.27 (br d, J=8.9 Hz, 1H), 5.05 - 4.83 (m, 1H), 3.60 (br s, 1H), 2.99 (br s, 1H), 2.58 (br t, J=5.2 Hz, 3H), 2.52 (br s, 1H), 2.18 - 2.12 (m, 1H), 2.08 (br d, J=9.8 Hz, 4H), 1.72 - 1.62 (m, 1H), 1.45 - 1.32 (m, 4H), 1.23 - 1.14 (m, 1H); | J |
| 509 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (br s, 1H), 11.16 (s, 1H), 8.62 (d, J=7.1 Hz, 1H), 7.79 (s, 1H), 7.64 (d, J=0.9 Hz, 1H), 6.91 (s, 1H), 6.85 (dd, J=2.0, 7.1 Hz, 1H), 5.10 - 4.81 (m, 1H), 4.31 (br d, J=6.8 Hz, 2H), 2.23 (d, J=3.1 Hz, 3H), 2.14 (td, J=6.9, 13.9 Hz, 1H), 1.73 - 1.61 (m, 1H), 1.39 (t, J=7.0 Hz, 3H), 1.17 (tdd, J=6.2, 9.1, 12.3 Hz, 1H); LCMS(電灑) m/z 412.2 (M +H+). | J |
| 510 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.16 - 12.81 (m, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.84 (s, 1H), 7.72 - 7.66 (m, 1H), 6.95 - 6.86 (m, 2H), 6.00 - 5.59 (m, 2H), 5.17 - 4.76 (m, 1H), 2.21 - 2.09 (m, 1H), 1.76 - 1.59 (m, 1H), 1.43 - 1.36 (m, 1H), 1.26 - 1.11 (m, 1H); LCMS(電灑) m/z 403.1 (M+H+). | J |
| 511 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.28 (s, 1H), 11.12 (s, 1H), 8.58 (d, J = 7.1 Hz, 1H), 7.70 (d, J = 1.2 Hz, 1H), 7.57 (dd, J = 0.9, 1.7 Hz, 1H), 6.87 (s, 1H), 6.84 - 6.79 (m, 2H), 5.05 - 4.83 (m, 1H), 4.27 (q, J = 7.0 Hz, 2H), 2.34 (s, 3H), 2.19 - 2.09 (m, 1H), 1.72 - 1.61 (m, 1H), 1.46 (t, J = 7.0 Hz, 3H), 1.17 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS(電灑) m/z 393.9 (M+H+). | J |
| 512 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.27 (br s, 1H), 11.15 (s, 1H), 9.49 (br s, 1H), 8.62 (d, J=7.1 Hz, 1H), 7.88 (br s, 1H), 7.69 (d, J=1.0 Hz, 1H), 6.93 (s, 1H), 6.90 (dd, J=2.0, 7.2 Hz, 1H), 5.33 (br s, 1H), 5.11 - 4.77 (m, 1H), 3.19 (br d, J=9.0 Hz, 1H), 2.77 (s, 3H), 2.76 (s, 3H), 2.52 (d, J=2.0 Hz, 1H), 2.12 (br d, J=11.7 Hz, 3H), 2.04 (br d, J=10.8 Hz, 2H), 1.72 - 1.61 (m, 1H), 1.61 - 1.51 (m, 2H), 1.46 - 1.32 (m, 2H), 1.17 (tdd, J=6.2, 9.0, 12.4 Hz, 1H); LCMS(電灑) m/z 528.3 (M +H+). | J |
| 513 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (s, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.76 (s, 1H), 7.64 (s, 1H), 6.93 (s, 1H), 6.82 (d, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 2.69 - 2.62 (m, 2H), 2.50 (s, 3H), 2.16 - 2.12 (m, 1H), 1.70 - 1.63 (m, 1H), 1.28 - 1.12 (m, 1H), 1.12 - 1.08 (m, 3H); LCMS (電灑) m/z 428.1 (M+H)+. | J |
| 514 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.63 - 13.08 (m, 1H), 11.19 (s, 1H), 8.67 (td, J = 1.0, 7.1 Hz, 1H), 8.03 - 7.86 (m, 1H), 7.83 - 7.56 (m, 4H), 7.06 - 6.86 (m, 2H), 5.14 - 4.81 (m, 2H), 3.24 - 3.15 (m, 1H), 2.95 - 2.84 (m, 4H), 2.15 (td, J = 7.0, 13.9 Hz, 1H), 2.02 - 1.91 (m, 2H), 1.86 - 1.74 (m, 2H), 1.73 - 1.45 (m, 4H), 1.41 - 1.28 (m, 1H), 1.25 - 1.12 (m, 1H); LCMS(電灑) m/z 514.1 (M +H+). | J |
| 515 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.32 (br d, J = 13.8 Hz, 1H), 11.16 (s, 1H), 8.63 (br d, J = 6.9 Hz, 1H), 7.95 - 7.60 (m, 5H), 6.99 - 6.79 (m, 2H), 5.35 - 4.78 (m, 2H), 4.09 - 3.63 (m, 1H), 4.05 - 3.45 (m, 1H), 3.24 - 2.98 (m, 3H), 2.15 (td, J = 6.9, 13.7 Hz, 1H), 2.09 - 1.93 (m, 2H), 1.77 (br s, 3H), 1.72 - 1.61 (m, 1H), 1.53 - 1.34 (m, 2H), 1.26 - 1.14 (m, 1H); LCMS(電灑) m/z 500.4 (M +H+). | J |
| 516 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.54 - 12.40 (m, 1H), 11.16 (s, 1H), 8.62 (d, J = 7.3 Hz, 1H), 7.98 - 7.77 (m, 1H), 7.71 (br s, 1H), 7.02 - 6.86 (m, 2H), 6.84 - 6.66 (m, 1H), 5.07 - 4.82 (m, 1H), 3.47 (br s, 2H), 3.26 (br s, 1H), 2.15 (td, J = 6.8, 13.6 Hz, 1H), 1.99 (br d, J = 10.3 Hz, 1H), 1.82 (br d, J = 10.4 Hz, 1H), 1.74 - 1.62 (m, 4H), 1.55 (br d, J = 10.4 Hz, 1H), 1.39 (d, J = 5.1 Hz, 9H), 1.36 - 1.11 (m, 3H); LCMS(電灑) m/z 600.1 (M +H+). | J |
| 517 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 - 12.88 (m, 1H), 11.24 - 11.06 (m, 1H), 8.71 - 8.53 (m, 1H), 7.93 - 7.64 (m, 2H), 7.05 - 6.57 (m, 2H), 5.10 - 4.69 (m, 1H), 3.92 - 3.72 (m, 3H), 2.27 - 2.08 (m, 1H), 1.81 - 1.45 (m, 8H), 1.34 - 1.09 (m, 2H); LCMS(電灑) m/z 501.1 (M +H+). | J |
| 518 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (br s, 1H), 11.15 (s, 1H), 8.62 (d, J=7.1 Hz, 1H), 7.68 (br s, 1H), 7.62 (s, 1H), 6.91 (s, 1H), 6.83 (dd, J=1.8, 7.1 Hz, 1H), 5.06 - 4.82 (m, 1H), 3.26 (br d, J=6.1 Hz, 4H), 2.61 (br d, J=7.1 Hz, 2H), 2.19 - 2.10 (m, 1H), 1.74 - 1.60 (m, 1H), 1.21 - 1.14 (m, 1H), 1.10 (t, J=7.4 Hz, 3H), 0.99 (t, J=7.1 Hz, 6H); LCMS(電灑) m/z 453.4(M+H+). | J |
| 519 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.99 - 12.38 (m, 1H), 11.14 (s, 1H), 8.61 (d, J=7.1 Hz, 1H), 7.68 (s, 1H), 7.58 (d, J=0.9 Hz, 1H), 6.90 (s, 1H), 6.79 (dd, J=1.9, 7.0 Hz, 1H), 5.11 - 4.76 (m, 1H), 2.97 (s, 3H), 2.97 (s, 3H), 2.65 - 2.53 (m, 2H), 2.14 (td, J=6.9, 13.8 Hz, 1H), 1.75 - 1.60 (m, 1H), 1.22 - 1.14 (m, 1H), 1.10 (t, J=7.4 Hz, 3H); LCMS(電灑) m/z425.2 (M +H+). | J |
| 520 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.79 (br s, 1H), 11.18 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 7.99 (br s, 1H), 7.80 (d, J = 0.7 Hz, 1H), 6.98 (s, 1H), 6.96 (dd, J = 1.9, 7.2 Hz, 1H), 5.06 - 4.82 (m, 1H), 3.53 (t, J = 6.7 Hz, 2H), 3.12 - 3.04 (m, 2H), 2.15 (td, J = 7.1, 13.8 Hz, 1H), 1.73 - 1.61 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS(電灑) m/z 464 (M+H+). | J |
| 521 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.62 (s, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 8.07 (d, 1H), 7.78 (s, 1H), 7.65 (d, 1H), 6.94 (s, 1H), 6.83 (dd, 1H), 5.08 - 4.83 (m, 1H), 3.64 (s, 2H), 2.63 (d, 2H), 2.60 (d, 3H), 2.20 - 2.11 (m, 1H), 1.75 - 1.61 (m, 1H), 1.24 - 1.15 (m, 1H), 1.11 (t, 3H); LCMS(電灑) m/z 485.2 (M+H+). | J |
| 522 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.72 - 13.26 (m, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.78 (s, 1H), 7.64 (d, J = 0.8 Hz, 1H), 6.95 (s, 1H), 6.82 (dd, J = 1.9, 7.1 Hz, 1H), 5.13 - 4.76 (m, 1H), 3.97 (s, 2H), 3.02 (s, 3H), 2.83 (s, 3H), 2.66 - 2.59 (m, 2H), 2.19 - 2.08 (m, 1H), 1.74 - 1.61 (m, 1H), 1.23 - 1.15 (m, 1H), 1.11 (t, J = 7.4 Hz, 3H); LCMS(電灑) m/z 499.4 (M+H+). | J |
| 523 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.46 (s, 1H), 11.16 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.84 (s, 1H), 7.68 (d, J = 0.7 Hz, 1H), 6.93 (s, 1H), 6.88 (dd, J = 2.0, 7.1 Hz, 1H), 5.08 - 4.81 (m, 2H), 3.51 (t, J = 6.9 Hz, 2H), 3.01 (br t, J = 6.8 Hz, 2H), 2.24 (d, J = 2.9 Hz, 3H), 2.15 (td, J = 6.9, 14.0 Hz, 1H), 1.73 - 1.61 (m, 1H), 1.17 (tdd, J = 6.2, 9.0, 12.3 Hz, 1H); LCMS(電灑) m/z 444.1 (M+H+). | J |
| 524 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.13 (s, 1H), 8.58 (d, J = 7.1 Hz, 1H), 7.67 (s, 1H), 7.55 (d, J = 0.8 Hz, 1H), 6.88 (s, 1H), 6.78 (dd, J = 1.9, 7.1 Hz, 1H), 5.06 - 4.82 (m, 1H), 3.50 (q, J = 7.0 Hz, 2H), 2.60 (br d, J = 7.6 Hz, 2H), 2.14 (td, J = 7.2, 13.9 Hz, 1H), 1.74 - 1.59 (m, 1H), 1.22 - 1.07 (m, 7H); LCMS(電灑) m/z 425.2 (M+H+). | J |
| 525 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.48 - 12.86 (m, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.0 Hz, 1H), 7.68 (s, 1H), 7.60 (d, J = 0.9 Hz, 1H), 6.91 (s, 1H), 6.81 (dd, J = 1.9, 7.0 Hz, 1H), 5.08 - 4.79 (m, 1H), 3.23 (q, J = 7.0 Hz, 2H), 2.95 (d, J = 1.6 Hz, 3H), 2.60 (br d, J = 7.1 Hz, 2H), 2.18 - 2.10 (m, 1H), 1.72 - 1.61 (m, 1H), 1.20 - 1.14 (m, 1H), 1.12 - 1.04 (m, 6H); LCMS(電灑) m/z 439.2 (M+H+). | J |
| 526 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 - 13.32 (m, 1H), 13.12 - 12.20 (m, 1H), 11.17 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.79 (s, 1H), 7.65 (d, J = 0.9 Hz, 1H), 6.94 (s, 1H), 6.83 (dd, J = 2.0, 7.1 Hz, 1H), 5.07 - 4.82 (m, 1H), 3.77 (br s, 2H), 2.63 (br d, J = 6.8 Hz, 2H), 2.21 - 2.09 (m, 1H), 1.74 - 1.61 (m, 1H), 1.24 - 1.14 (m, 1H), 1.10 (t, J = 7.4 Hz, 3H); LCMS(電灑) m/z 472.1 (M+H+). | J |
| 527 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.64 - 13.45 (m, 1H), 11.24 - 11.12 (m, 1H), 8.72 - 8.62 (m, 1H), 8.02 - 7.73 (m, 4H), 7.03 - 6.89 (m, 2H), 5.13 - 4.83 (m, 1H), 2.88 (br d, J = 17.4 Hz, 2H), 2.08 (s, 5H), 2.04 - 1.93 (m, 2H), 1.75 - 1.58 (m, 3H), 1.28 - 1.18 (m, 3H); LCMS(電灑) m/z 500.1 (M +H+). | J |
| 528 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.75 (s, 1H), 7.88 (s, 1H), 7.82 - 7.76 (m, 1H), 7.74 - 7.68 (m, 1H), 2.19 - 2.11 (m, 1H), 1.92 - 1.81 (m, 1H), 1.35 - 1.22 (m, 2H); LCMS(電灑) m/z 404.1 (M+H+). | J |
| 529 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.68 (s, 1H), 11.16 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.88 (d, J = 1.3 Hz, 1H), 7.68 (d, J = 1.0 Hz, 1H), 6.94 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.07 - 4.82 (m, 1H), 2.54 (s, 3H), 2.28 (s, 3H), 2.19 - 2.10 (m, 1H), 1.79 - 1.57 (m, 1H), 1.26 - 1.12 (m, 1H); LCMS(電灑) m/z 446.0 (M +H+). | J |
| 530 |  | 1H NMR (400MHz, CHLOROFORM-d) δ 13.40 (br s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.81 (s, 1H), 7.67 (dd, J = 0.7, 1.7 Hz, 1H), 7.52 (dd, J = 0.9, 9.3 Hz, 1H), 6.93 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.06 - 4.82 (m, 1H), 2.26 (s, 3H), 2.15 (td, J = 7.0, 13.9 Hz, 1H), 1.75 - 1.61 (m, 1H), 1.21 - 1.14 (m, 1H); LCMS(電灑) m/z 400.1 (M +H+). | J |
| 531 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.48 (s, 1H), 11.16 (s, 1H), 8.63 (d, J = 6.8 Hz, 1H), 7.72 (s, 1H), 7.61 (s, 1H), 6.92 (s, 1H), 6.81 (dd, J = 7.2, 2.0 Hz, 1H), 5.04 - 4.85 (m, 1H), 4.34 - 4.29 (m, 2H), 2.64 - 2.60 (m, 2H), 2.17 - 2.13 (m, 1H), 1.75 - 1.65 (m, 1H), 1.40 (t, J = 7.2 Hz, 3H), 1.19 - 1.15 (m, 1H), 1.12 (t, J = 7.2Hz, 3H); LCMS(電灑) m/z 426.2 (M +H+). | J |
| 532 |  | 1H NMR (400 MHz, CHLOROFORM-d) δ 8.46 - 8.41 (m, 1 H), 8.37 (d, J=7.09 Hz, 1 H), 7.80 - 7.74 (m, 1 H), 7.45 (d, J=0.86 Hz, 1 H), 7.09 (s, 1 H), 6.73 (dd, J=7.03, 1.90 Hz, 1 H), 5.00 - 4.72 (m, 1 H), 2.81 - 2.64 (m, 2 H), 2.01 - 1.94 (m, 1 H), 1.92 - 1.89 (m, 1 H), 1.28 - 1.25 (m, 1 H), 1.18 (t, J=7.46 Hz, 3 H); LCMS(電灑) m/z 400.0 (M +H+). | J |
| 533 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.18 (s, 1H), 8.67 (d, J = 7.0 Hz, 1H), 7.91 (s, 1H), 7.71 (s, 1H), 6.96 (s, 1H), 6.89 (dd, J = 1.9, 7.1 Hz, 1H), 5.15 - 4.65 (m, 1H), 3.13 (s, 3H), 2.24 (d, J = 2.8 Hz, 3H), 2.15 (td, J = 7.0, 14.1 Hz, 1H), 1.76 - 1.58 (m, 1H), 1.26 - 1.10 (m, 1H); LCMS(電灑) m/z 429.11 (M +H+). | J |
| 534 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.39 (br s, 1H), 14.04 - 12.74 (m, 1H), 11.15 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.80 (s, 1H), 7.64 (d, J = 0.9 Hz, 1H), 7.29 (dd, J = 2.0, 7.3 Hz, 1H), 6.96 - 6.90 (m, 1H), 6.86 (dd, J = 1.8, 7.1 Hz, 1H), 5.06 - 4.83 (m, 1H), 4.30 (br t, J = 4.9 Hz, 2H), 3.78 (t, J = 5.1 Hz, 2H), 2.24 (d, J = 3.1 Hz, 3H), 2.20 - 2.08 (m, 1H), 1.75 - 1.58 (m, 1H), 1.25 - 1.13 (m, 1H); LCMS(電灑) m/z 428.0 (M +H+). | J |
| 535 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.41 (d, J = 7.1 Hz, 1H), 7.66 (s, 1H), 7.44 (s, 1H), 6.83 (s, 1H), 6.74 (dd, J = 1.7, 7.1 Hz, 1H), 4.86 (td, J = 3.1, 6.3 Hz, 1H), 4.69 (dt, J = 3.9, 6.2 Hz, 1H), 4.46 - 4.38 (m, 2H), 4.33 - 4.25 (m, 2H), 3.89 - 3.80 (m, 1H), 2.20 - 2.16 (m, 1H), 2.18 (d, J = 3.2 Hz, 2H), 2.00 (td, J = 6.9, 13.8 Hz, 1H), 1.78 - 1.62 (m, 1H), 1.19 - 1.04 (m, 1H); LCMS(電灑) m/z 471.1 (M +H+). | J |
| 536 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.19 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 7.67 (s, 1H), 6.96 (s, 1H), 6.87 (s, 1H), 6.79 (dd, J = 2.0, 7.2 Hz, 1H), 5.08 - 4.79 (m, 1H), 2.19 - 2.08 (m, 1H), 1.74 - 1.59 (m, 1H), 1.28 - 1.09 (m, 2H); LCMS(電灑) m/z 406.2 (M +H+). | J |
| 537 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.31 (br s, 1H), 11.27 - 11.11 (m, 1H), 10.14 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.91 (s, 1H), 7.80 (d, J = 0.9 Hz, 1H), 6.97 (s, 1H), 6.95 (dd, J = 1.9, 7.2 Hz, 1H), 5.09 - 4.82 (m, 1H), 2.18 (s, 3H), 2.16 - 2.10 (m, 1H), 1.75 - 1.61 (m, 1H), 1.18 (ddd, J = 2.7, 6.1, 12.5 Hz, 1H); LCMS(電灑) m/z 445.2 (M +H+). | J |
| 538 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.73 (br s, 1H), 11.22 (s, 1H), 8.72 (d, J = 7.0 Hz, 1H), 8.06 (s, 1H), 7.83 (d, J = 1.0 Hz, 1H), 7.01 (s, 1H), 6.97 (dd, J = 2.0, 7.2 Hz, 1H), 5.08 - 4.83 (m, 1H), 3.20 (s, 3H), 2.16 (td, J = 7.0, 14.0 Hz, 1H), 1.75 - 1.60 (m, 1H), 1.24 - 1.13 (m, 1H); LCMS(電灑) m/z 450 (M+H+). | J |
| 539 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.15 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.80 (s, 1H), 7.63 (d, J = 0.7 Hz, 1H), 6.91 (s, 1H), 6.85 (dd, J = 1.9, 7.2 Hz, 1H), 6.06 - 5.88 (m, 1H), 5.05 - 4.82 (m, 1H), 4.33 (br t, J = 5.4 Hz, 2H), 3.62 (br t, J = 5.8 Hz, 5H), 2.94 (s, 3H), 2.23 (d, J = 3.1 Hz, 3H), 2.18 - 2.11 (m, 1H), 1.73 - 1.61 (m, 1H), 1.20 - 1.14 (m, 1H); LCMS(電灑) m/z 484.4 (M+H+). | J |
| 540 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.95 (s, 1H), 11.16 (s, 1H), 9.93 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.76 (s, 1H), 7.67 (s, 1H), 6.93 (s, 1H), 6.87 (dd, J = 1.7, 7.1 Hz, 1H), 5.06 - 4.82 (m, 1H), 2.24 (d, J = 2.6 Hz, 3H), 2.20 - 2.10 (m, 4H), 1.73 - 1.60 (m, 1H), 1.17 (tdd, J = 6.4, 9.0, 12.3 Hz, 1H); LCMS(電灑) m/z 424.15 (M +H+). | J |
| 541 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.96 (br s, 1H), 7.66 (d, J = 1.0 Hz, 1H), 6.94 (s, 1H), 6.88 (dd, J = 2.0, 7.1 Hz, 1H), 5.06 - 4.83 (m, 1H), 2.30 (s, 3H), 2.15 (td, J = 7.0, 14.0 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.17 (tdd, J = 6.3, 9.0, 12.3 Hz, 1H); LCMS(電灑) m/z 418 (M +H+). | J |
| 542 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.97 (s, 1H), 11.16 (s, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.35 (s, 1H), 7.88 (s, 1H), 7.71 (s, 1H), 6.93 (s, 1H), 6.89 (d, J = 7.2 Hz, 1H), 5.04 - 4.85 (m, 1H), 3.23 (s, 3H), 2.16 - 2.12 (m, 1H), 1.70 - 1.63 (m, 1H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 532.1 (M+H)+. | J |
| 543 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.02 - 13.34 (m, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.85 (s, 1H), 7.65 (s, 1H), 6.93 (s, 1H), 6.89 (dd, J = 1.8, 7.1 Hz, 1H), 5.11 - 4.78 (m, 1H), 4.35 (q, J = 7.0 Hz, 2H), 2.28 (s, 3H), 2.19 - 2.12 (m, 1H), 1.68 (m, J = 3.2, 6.8, 19.9 Hz, 1H), 1.41 (t, J = 7.0 Hz, 3H), 1.26 - 1.11 (m, 1H); LCMS(電灑) m/z 444.2 (M+H+). | J |
| 544 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.15 (s, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.80 (s, 1H), 7.64 (d, J = 1.0 Hz, 1H), 6.91 (s, 1H), 6.85 (dd, J = 1.9, 7.1 Hz, 1H), 6.28 (br s, 1H), 5.14 - 4.71 (m, 1H), 4.22 (t, J = 5.4 Hz, 2H), 3.40 (br d, J = 4.1 Hz, 2H), 2.24 (d, J = 3.0 Hz, 3H), 2.19 - 2.09 (m, 1H), 1.73 - 1.59 (m, 1H), 1.24 - 1.07 (m, 1H); LCMS(電灑) m/z 470.1 (M +H+). | J |
| 545 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.24 - 11.04 (m, 1H), 8.74 - 8.52 (m, 1H), 7.85 - 7.75 (m, 1H), 7.64 (d, J = 0.9 Hz, 1H), 6.91 (s, 1H), 6.85 (dd, J = 1.8, 7.1 Hz, 1H), 6.27 - 6.15 (m, 1H), 6.03 - 5.80 (m, 1H), 5.09 - 4.80 (m, 1H), 4.31 - 4.12 (m, 2H), 3.47 - 3.34 (m, 2H), 2.57 (s, 3H), 2.23 (d, J = 3.1 Hz, 3H), 2.19 - 2.08 (m, 1H), 1.75 - 1.60 (m, 1H), 1.25 - 1.10 (m, 1H); LCMS(電灑) m/z 484.2 (M +H+). | J |
| 546 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.52 - 13.40 (m, 1H), 11.16 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.85 (br s, 1H), 7.68 (s, 1H), 6.94 (s, 1H), 6.89 (dd, J = 1.6, 7.0 Hz, 1H), 5.04 - 4.83 (m, 1H), 4.05 (br t, J = 6.7 Hz, 2H), 3.16 (br d, J = 5.5 Hz, 2H), 2.53 (br s, 3H), 2.25 (d, J = 2.7 Hz, 3H), 2.17 - 2.13 (m, 1H), 2.04 (td, J = 2.4, 4.9 Hz, 1H), 1.68 (tdd, J = 3.3, 6.6, 19.7 Hz, 1H), 1.17 (ddd, J = 2.6, 6.2, 12.3 Hz, 1H); LCMS(電灑) m/z 501.2 (M +H+). | J |
| 547 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.67 - 13.25 (m, 1H), 11.16 (s, 1H), 9.63 (br t, J = 5.2 Hz, 1H), 8.63 (d, J = 7.1 Hz, 1H), 7.82 (s, 1H), 7.64 (d, J = 0.9 Hz, 1H), 6.92 (s, 1H), 6.85 (dd, J = 1.9, 7.2 Hz, 1H), 5.07 - 4.83 (m, 1H), 4.38 ( s, 2H), 3.66 (q, J = 5.5 Hz, 3H), 2.23 (d, J = 3.1 Hz, 3H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.75 - 1.61 (m, 1H), 1.18-1.29 (m, J = 2.9, 6.1, 12.3 Hz, 1H); LCMS(電灑) m/z 523.3 (M+H+). | J |
| 548 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.32 (s, 1H), 11.19 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.89 (s, 1H), 7.73 (s, 1H), 6.96 (s, 1H), 6.89 (dd, J = 1.8, 7.1 Hz, 1H), 5.15- 4.72 (m, 1H), 3.98 (s, 3H), 2.24 (d, J = 2.9 Hz, 3H), 2.20 - 2.09 (m, 1H), 1.76 - 1.59 (m, 1H), 1.18 (ddd, J = 2.8, 6.2, 12.2 Hz,1H); LCMS(電灑) m/z 426.2 (M+H+). | J |
| 549 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.66 - 13.38 (m, 1H), 13.19 (br s, 1H), 11.19 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.85 (s, 1H), 7.72 (s, 1H), 6.96 (s, 1H), 6.89 (dd,J = 1.8, 7.1 Hz, 1H), 5.07 - 4.84 (m, 1H), 2.24 (d, J = 3.1 Hz, 3H), 2.18 - 2.13 (m, 1H), 1.72 - 1.62 (m, 1H), 1.20 - 1.14 (m, 1H); LCMS(電灑) m/z 412.2 (M+H+). | J |
| 550 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.22 - 11.13 (m, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.95 - 7.87 (m, 1H), 7.72 - 7.70 (m, 1H), 6.96 - 6.93 (m, 1H), 6.92 - 6.89 (m, 1H), 5.07 - 4.81 (m, 1H), 3.21 (s, 3H), 2.30 - 2.25 (m, 3H), 2.25 - 2.23 (m, 1H), 2.20 - 2.09 (m, 1H), 1.79 (s, 3H), 1.74 - 1.63 (m, 1H), 1.28 - 1.09 (m, 1H); LCMS(電灑) m/z 438.16 (M +H+). | J |
| 551 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (br s, 1H), 11.20 (s, 1H), 8.70 (d, J = 7.1 Hz, 1H), 7.99 (s, 1H), 7.83 (d, J = 0.9 Hz, 1H), 7.03 - 6.95 (m, 2H), 5.10 - 4.82 (m, 1H), 2.22 - 2.09 (m, 1H), 1.79 - 1.60 (m, 1H), 1.26 - 1.11 (m, 1H); LCMS(電灑) m/z 432.2 (M +H+). | J |
| 552 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.07 - 13.87 (m, 1H), 11.19 (s, 1H), 8.69 (br d, J = 7.1 Hz, 1H), 8.07 - 8.01 (m, 1H), 7.82 (d, J = 0.7 Hz, 1H), 6.99 (s, 1H), 6.97 (br d, J = 2.0 Hz, 1H), 5.05 - 4.83 (m, 1H), 3.23 (s, 3H), 2.18 - 2.11 (m, 1H), 1.82 (s, 3H), 1.71 - 1.64 (m, 1H), 1.22 - 1.13 (m, 1H); LCMS(電灑) m/z 459.2 (M +H+). | J |
| 553 |  | 1H NMR (400 MHz, DMSO-d 6) δ 12.95 (s, 1H), 11.15 (s, 1H), 8.60 (d, J = 7.2 Hz, 1H), 7.77 (s, 1H), 7.68 (s, 1H), 7.42 (s, 1H), 6.91 - 6.88 (m, 2H), 5.02 (s, 1H), 5.04 - 4.85 (m, 1H), 2.66 (s, 3H), 2.16 - 2.12 (m, 1H), 1.70 - 1.63 (m, 1H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 432.1 (M+H)+. | J |
| 554 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.22 (s, 1H), 8.71 (d, J = 7.1 Hz, 1H), 8.05 (s, 1H), 7.85 (d, J = 1.0 Hz, 1H), 7.00 (s, 1H), 6.97 (dd, J = 2.0, 7.2 Hz, 1H), 5.08 - 4.81 (m, 1H), 4.00 (s, 3H), 2.19 - 2.11 (m, 1H), 1.75 - 1.60 (m, 1H), 1.21 - 1.13 (m, 1H); LCMS(電灑) m/z 446.0 (M +H+). | J |
| 555 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (br s, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.0 Hz, 1H), 7.89 (s, 1H), 7.77 (s, 1H), 7.04 - 6.89 (m, 2H), 5.15 - 4.82 (m, 1H), 4.58 (d, J = 4.3 Hz, 1H), 4.08 (br d, J = 5.4 Hz, 1H), 3.70 (br s, 1H), 2.90 (s, 3H), 2.11 (dt, J = 7.0, 13.6 Hz, 2H), 1.81 - 1.62 (m, 5H), 1.59 - 1.43 (m, 2H), 1.25 - 1.13 (m, 1H); LCMS(電灑) m/z 501.2 (M +H+). | J |
| 556 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.88 - 13.56 (m, 1H), 11.20 (s, 1H), 8.70 (d, J = 7.1 Hz, 1H), 8.00 (s, 1H), 7.82 (d, J = 0.7 Hz, 1H), 6.99 (s, 1H), 6.96 (d, J = 2.0 Hz, 1H), 5.05 - 4.85 (m, 1H), 3.13 (s, 3H), 2.93 (s, 3H), 2.18 - 2.11 (m, 1H), 1.72 - 1.62 (m, 1H), 1.18 (ddd, J = 2.9, 6.1, 12.3 Hz, 1H); LCMS(電灑) m/z459.1(M +H+). | J |
| 557 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.18 (br d, J = 2.5 Hz, 1H), 11.14 (s, 1H), 8.62 (d, J = 7.2 Hz, 1H), 7.74 (s, 1H), 7.62 (s, 1H), 6.90 (s, 1H), 6.87 - 6.81 (m, 1H), 5.17 - 4.73 (m, 2H), 3.65 - 3.57 (m, 2H), 3.28 - 3.18 (m, 2H), 2.97 (d, J = 2.3 Hz, 3H), 2.25 - 2.10 (m, 4H), 1.76 - 1.58 (m, 1H), 1.26 - 1.11 (m, 1H); LCMS(電灑) m/z 441.1 (M +H+). | J |
| 558 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.43 (br s, 1H), 11.14 (s, 1H), 8.59 (d, J = 7.0 Hz, 1H), 7.78 (s, 1H), 7.62 (s, 1H), 6.91 (s, 1H), 6.87 (dd, J = 1.9, 7.1 Hz, 1H), 5.06 - 4.82 (m, 1H), 2.97 (d, J = 2.0 Hz, 6H), 2.26 (s, 3H), 2.19 - 2.10 (m, 1H), 1.73 - 1.61 (m, 1H), 1.22 - 1.12 (m, 1H); LCMS(電灑) m/z 443 (M+H+). | J |
| 559 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.29 (br s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.0 Hz, 1H), 7.86 (br s, 1H), 7.71 (s, 1H), 7.00 - 6.86 (m, 2H), 5.44 (br s, 1H), 5.11 - 4.94 (m, 1H), 4.90 - 4.77 (m, 1H), 4.40 - 4.11 (m, 2H), 2.25 - 2.09 (m, 2H), 2.04 - 1.86 (m, 1H), 1.84 - 1.57 (m, 5H), 1.30 - 1.08 (m, 1H); LCMS(電灑) m/z 487.2 (M +H+). | J |
| 560 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.68 - 13.53 (m, 1H), 11.24 - 11.17 (m, 1H), 8.70 (d, J = 7.1 Hz, 1H), 8.67 - 8.60 (m, 1H), 7.99 - 7.93 (m, 1H), 7.81 (d, J = 0.9 Hz, 1H), 6.99 (s, 1H), 6.97 - 6.92 (m, 1H), 5.07 - 4.81 (m, 1H), 2.91 (d, J = 4.4 Hz, 3H), 2.20 - 2.10 (m, 1H), 1.75 - 1.55 (m, 1H), 1.07 (s, 1H); LCMS(電灑) m/z 445.1(M +H+). | J |
| 561 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.18 (br s, 1H), 8.65 (d, J = 7.2 Hz, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 7.09 - 6.87 (m, 2H), 5.08 - 4.84 (m, 1H), 3.87 - 3.71 (m, 1H), 3.59 - 3.43 (m, 1H), 3.60 - 3.42 (m, 1H), 2.89 - 2.81 (m, 3H), 2.46 - 2.39 (m, 2H), 2.21 - 2.09 (m, 1H), 2.24 - 2.07 (m, 1H), 2.20 - 1.95 (m, 1H), 1.99 (br d, J = 4.9 Hz, 1H), 1.79 - 1.62 (m, 3H), 1.26 - 1.12 (m, 2H); LCMS(電灑) m/z 487.2 (M +H+). | J |
| 562 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (br s, 1H), 11.11 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.83 (s, 1H), 7.65 (s, 1H), 6.91 (s, 1H), 6.86 (dd, J = 1.9, 7.1 Hz, 1H), 2.24 (d, J = 2.9 Hz, 3H), 2.00 - 1.87 (m, 1H), 0.88 - 0.77 (m, 4H); LCMS(電灑) m/z 395.12 (M +H+). | J |
| 563 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.55 - 8.47 (m, 1H), 7.79 - 7.72 (m, 1H), 7.58 - 7.54 (m, 1H), 7.00 - 6.93 (m, 1H), 6.89 - 6.83 (m, 1H), 5.02 - 4.93 (m, 1H), 4.60 - 4.56 (m, 1H), 3.29 - 3.24 (m, 2H), 3.01 - 2.94 (m, 3H), 2.33 - 2.25 (m, 3H), 2.17 - 2.07 (m, 1H), 1.89 - 1.77 (m, 1H), 1.27 - 1.19 (m, 1H), 1.15 - 1.09 (m, 3H); LCMS(電灑) m/z 425.2 (M +H+). | J |
| 564 |  | 1H NMR (400 MHz, METHANOL-d 4) δ 8.43 - 8.38 (m, 1H), 7.77 - 7.72 (m, 1H), 7.59 - 7.54 (m, 1H), 6.89 - 6.86 (m, 1H),6.85 - 6.81 (m, 1H), 4.88 - 4.82 (m, 1H), 4.72 - 4.64 (m, 1H), 3.20 - 3.15 (m, 2H), 3.20 (br s, 1H), 2.90 (d, J = 1.8 Hz, 2H), 2.95 -2.88 (m, 1H), 2.04 - 1.94 (m, 1H), 1.78 - 1.65 (m, 1H), 1.17 - 1.07 (m, 1H), 1.05 - 0.99 (m, 3H); LCMS(電灑) m/z 445.2 (M +H+). | J |
| 565 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.18 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 7.80 (d, J = 4.8 Hz, 1H), 7.62 (d, J = 0.9 Hz, 1H), 6.92 (s, 1H), 6.80 (dd, J = 1.9, 7.1 Hz, 1H), 5.08 - 4.70 (m, 1H), 3.02 (d, J = 2.3 Hz, 6H), 2.20 - 2.12 (m, 1H), 1.73 - 1.62 (m, 1H), 1.22 - 1.14 (m, 1H); LCMS(電灑) m/z 465.1 (M+H+). | J |
| 566 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (br s, 1H), 11.19 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.86 (s, 1H), 7.73 (s, 1H), 6.97 (s, 1H), 6.89 (dd, J = 1.9, 7.2 Hz, 1H), 5.07 - 4.80 (m, 1H), 2.74 (d, J = 6.4 Hz, 3H), 2.28 (d, J = 3.2 Hz, 3H), 2.20 - 2.09 (m, 1H), 1.74 - 1.61 (m, 1H), 1.25 - 1.13 (m, 1H); LCMS(電灑) m/z 409.14 (M +H+). | J |
| 567 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (br s, 1H), 11.28 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.83 (s, 1H), 7.67 (s, 1H), 6.89 (s, 1H), 6.87 (d, J = 1.8 Hz, 1H), 5.03 - 4.81 (m, 1H), 2.23 (d, J = 2.8 Hz, 3H), 1.64 - 1.45 (m, 1H), 1.27 (qd, J = 6.5, 13.1 Hz, 1H); LCMS(電灑) m/z 413.11 (M +H+). | J |
| 568 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (br s, 1H), 11.28 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.83 (s, 1H), 7.67 (d, J = 0.7 Hz, 1H), 6.88 (s, 1H), 6.87 (d, J = 1.8 Hz, 1H), 5.04 - 4.79 (m, 1H), 2.49 - 2.40 (m, 3H), 2.23 (d, J = 2.8 Hz, 3H), 1.62 - 1.45 (m, 1H), 1.27 (qd, J = 6.4, 13.1 Hz, 1H); LCMS(電灑) m/z 413.11 (M +H+). | J |
| 569 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.45 (br s, 1H), 11.10 (s, 1H), 8.61 (d, J=7.1 Hz, 1H), 7.81 (s, 1H), 7.66 (s, 1H), 7.52 (d, J=9.3 Hz, 1H), 6.91 (s, 1H), 6.88 (dd, J=1.8, 7.1 Hz, 1H), 2.26 (s, 3H), 2.00 - 1.88 (m, 1H), 0.90 - 0.77 (m, 4H); LCMS(電灑) m/z 382.1(M+H+) | J |
| 570 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.43 (br s, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.1 Hz, 1H), 7.84 (s, 1H), 7.73 - 7.67 (m, 1H), 6.94 (s, 1H), 6.89 (dd, J = 2.0, 7.1 Hz, 1H), 5.16 - 4.74 (m, 1H), 3.12 (s, 3H), 2.92 (s, 3H), 2.24 (d, J = 2.9 Hz, 3H), 2.19 - 2.10 (m, 1H), 1.74 - 1.60 (m, 1H), 1.18 (tdd, J = 6.2, 9.1, 12.3 Hz, 1H); LCMS(電灑) m/z 439.2 (M+H+). | J |
| 571 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (br s, 1H), 11.28 (br s, 1H), 8.63 (d, J=7.1 Hz, 1H), 7.81 (s, 1H), 7.67 (s, 1H), 7.52 (d, J=9.3 Hz, 1H), 6.93 - 6.87 (m, 2H), 5.05 - 4.81 (m, 1H), 2.48 - 2.42 (m, 1H), 2.26 (s, 3H), 1.61 - 1.46 (m, 1H), 1.33 - 1.20 (m, 1H); LCMS(電灑) m/z 400.1(M+H+). | J |
| 572 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.40 (br s, 1H), 11.28 (s, 1H), 8.63 (d, J=7.0 Hz, 1H), 7.81 (s, 1H), 7.67 (s, 1H), 7.52 (d, J=9.2 Hz, 1H), 6.93 - 6.87 (m, 2H), 5.03 - 4.80 (m, 1H), 2.46 - 2.42 (m, 1H), 2.26 (s, 3H), 1.61 - 1.46 (m, 1H), 1.27 (qd, J=6.3, 13.0 Hz, 1H); LCMS(電灑) m/z 400.1(M+H+). | J |
| 573 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.42 (br s, 1H), 11.15 (s, 1H), 8.62 (d, J=7.0 Hz, 1H), 7.82 (s, 1H), 7.68 (s, 1H), 7.52 (d, J=9.4 Hz, 1H), 6.93 (s, 1H), 6.90 (dd, J=1.8, 7.1 Hz, 1H), 5.06 - 4.83 (m, 1H), 2.26 (s, 3H), 2.15 (td, J=7.1, 14.1 Hz, 1H), 1.74 - 1.61 (m, 1H), 1.22 - 1.12 (m, 1H); LCMS(電灑) m/z 400.1(M+H+). | J |
| 574 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.47 (br s, 1H), 11.16 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.84 (s, 1H), 7.67 (s, 1H), 6.93 (s, 1H), 6.87 (dd, J = 1.8, 7.1 Hz, 1H), 5.08 - 4.79 (m, 1H), 3.30 (s, 3H), 2.25 - 2.23 (m, 1H), 2.24 (d, J = 2.9 Hz, 3H), 2.14 (br dd, J = 6.0, 8.1 Hz, 1H), 1.76 - 1.60 (m, 1H), 1.24 - 1.13 (m, 1H); LCMS(電灑) m/z 413.11 (M +H+). | J |
| 575 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.74 (s, 1H), 11.22 (s, 1H), 8.72 (d, J = 7.1 Hz, 1H), 8.40 (s, 1H), 8.02 (s, 1H), 7.85 (d, J = 1.0 Hz, 1H), 7.02 (s, 1H), 6.97 (dd, J = 1.9, 7.2 Hz, 1H), 5.14 - 4.76 (m, 1H), 2.77 (d, J = 6.1 Hz, 3H), 2.21 - 2.12 (m, 1H), 1.75 - 1.61 (m, 1H), 1.26 - 1.12 (m, 2H); LCMS(電灑) m/z 430.3(M+H+). | J |
| 576 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 - 13.43 (m, 1H), 11.22 (s, 1H), 8.71 (d, J = 6.8 Hz, 1H), 8.08 (s, 2H), 7.95 (s, 1H), 7.82 (s, 1H), 7.03 - 6.91 (m, 2H), 5.10 - 4.81 (m, 1H), 2.15 (d, J = 6.8 Hz, 1H), 1.76 - 1.59 (m, 1H), 1.18 (d, J = 7.2 Hz, 1H); LCMS(電灑) m/z 431.1 (M+H+). | J |
| 577 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38 (br s, 1H), 11.14 (s, 1H), 8.60 (d, J = 6.9 Hz, 1H), 7.78 (s, 1H), 7.64 (s, 1H), 6.91 (s, 1H), 6.88 (dd, J = 1.6, 7.1 Hz, 1H), 5.06 - 4.83 (m, 1H), 3.23 (q, J = 6.7 Hz, 2H), 2.95 (s, 3H), 2.26 (s, 3H), 2.19 - 2.10 (m, 1H), 1.74 - 1.61 (m, 1H), 1.21 - 1.14 (m, 1H), 1.07 (t, J = 7.0 Hz, 3H); LCMS(電灑) m/z 457 (M+H+). | J |
| 578 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.62 - 12.96 (m, 1H), 11.16 (br s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.98 (s, 1H), 7.83 (s, 1H), 7.50 (d, J = 10.4 Hz, 1H), 7.04 (dd, J = 1.8, 7.1 Hz, 1H), 6.95 (s, 1H), 5.06 - 4.81 (m, 1H), 3.86 (q, J = 6.9 Hz, 2H), 2.15 (td, J = 7.0, 13.6 Hz, 1H), 1.73 - 1.62 (m, 1H), 1.22 - 1.15 (m, 1H), 1.11 (t, J = 7.0 Hz, 3H). LCMS: m/z 398.0 (M+H+) | J |
| 579 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.31 - 11.12 (m, 1H), 8.82 - 8.55 (m, 1H), 8.00 - 7.87 (m, 1H), 7.85 - 7.70 (m, 1H), 7.03 - 6.90 (m, 2H), 5.10 - 4.82 (m, 1H), 2.56 - 2.53 (m, 3H), 2.24 - 2.11 (m, 1H), 1.75 - 1.61 (m, 1H), 1.26 - 1.13 (m, 1H); LCMS(電灑) m/z 402.1 (M +H+). | J |
| 580 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.31 - 12.98 (m, 1H), 11.21 - 11.07 (m, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.78 - 7.71 (m, 1H), 7.64 - 7.58 (m, 1H), 6.93 - 6.88 (m, 2H), 6.84 (br d, J = 7.1 Hz, 1H), 5.06 - 4.82 (m, 1H), 4.07 (br t, J = 5.9 Hz, 2H), 3.35 - 3.27 (m, 2H), 2.98 (s, 3H), 2.53 (d, J = 4.5 Hz, 3H), 2.20 (d, J = 3.0 Hz, 3H), 2.16 - 2.09 (m, 1H), 1.72 - 1.61 (m, 1H), 1.20 - 1.13 (m, 1H); LCMS(電灑) m/z =498.2 (M +H+). | J |
| 581 |  | 1H NMR (400 MHz, DMSO-d 6) δ 1.12-1.24 (m, 1 H), 1.61-1.74 (m, 1 H), 2.11-2.20 (m, 1 H), 4.82-5.07 (m, 1 H), 6.95-6.98 (m, 1 H), 6.99 (s, 1 H), 7.50 (s, 1 H), 7.63 (s, 1 H), 7.77 (s, 1 H), 7.83 (d, J=1.00 Hz, 1 H), 8.06 (s, 1 H), 8.71 (d, J=7.13 Hz, 1 H), 11.20 (s, 1 H), 13.85-13.92 (m, 1 H); LCMS(電灑) m/z 438.1 (M+H+). | J |
| 582 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.19 (s, 1H), 8.69 (d, J = 7.1 Hz, 1H), 8.06 (s, 1H), 7.74 (s, 1H), 6.97 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.10 - 4.72 (m, 1H), 2.26 (d, J = 2.6 Hz, 3H), 2.15 (td, J = 6.6, 13.5 Hz, 1H), 1.73 - 1.60 (m, 1H), 1.25 - 1.13 (m, 1H); LCMS(電灑) m/z 393.1 (M+H+). | J |
| 583 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.38 (s, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 8.29 (s, 1H), 7.93 (d, J = 1.0 Hz, 1H), 7.23 (d, J = 13.7 Hz, 1H), 7.16 (dd, J = 2.0, 7.2 Hz, 1H), 6.94 (s, 1H), 5.06 - 4.83 (m, 1H), 2.95 (d, J = 2.0 Hz, 6H), 2.14 (br s, 1H), 1.77 - 1.57 (m, 1H), 1.17 (br s, 1H); LCMS(電灑) m/z 397.2 (M+H+). | J |
| 584 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.31 - 13.17 (m, 1H), 11.26 - 11.08 (m, 1H), 8.66 (d, J = 7.1 Hz, 1H), 8.49 - 8.38 (m, 1H), 7.85 - 7.76 (m, 1H), 7.70 (s, 1H), 6.95 (s, 1H), 6.88 (s, 1H), 5.07 - 4.82 (m, 1H), 2.90 (d, J = 4.6 Hz, 3H), 2.25 (d, J = 3.1 Hz, 3H), 2.15 (td, J = 6.7, 13.8 Hz, 1H), 1.74 - 1.62 (m, 1H), 1.21 - 1.09 (m, 1H); LCMS(電灑) m/z 425.1 (M +H+). | J |
| 585 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.82 - 13.52 (m, 1H), 11.19 (s, 1H), 8.69 (d, J = 7.0 Hz, 1H), 7.91 (s, 1H), 7.70 (d, J = 0.9 Hz, 1H), 6.96 (s, 1H), 6.86 (dd, J = 1.9, 7.1 Hz, 1H), 5.06 - 4.83 (m, 1H), 2.68 - 2.63 (m, 2H), 2.19 - 2.10 (m, 1H), 1.74 - 1.62 (m, 1H), 1.20 - 1.14 (m, 1H), 1.10 (t, J = 7.5 Hz, 3H); LCMS(電灑) m/z 450.2 (M +H+). | J |
| 586 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.21 (s, 1H), 8.73 (d, J = 7.2 Hz, 1H), 8.24 (s, 1H), 7.86 (s, 1H), 7.02 (s, 1H), 6.97 (dd, J= 1.9, 7.2 Hz, 1H), 5.10 - 4.78 (m,1H), 2.22 - 2.10 (m, 1H), 1.76 - 1.58 (m, 1H), 1.22 - 1.15 (m, 1H); LCMS(電灑) m/z 413.2 (M+H+). | J |
| 587 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.11 (s, 1H), 11.17 (s, 1H), 8.68 - 8.66 (m, 1H), 8.45(s, 1H), 8.04 (s, 1H), 7.52 (d, J=11.2 Hz, 1H), 7.22 - 7.21 (m, 1H), 6.99 (s, 1H), 5.02 - 4.86 (m, 1H), 2.15 (br s, 1H), 1.72 - 1.70 (m, 1 H) 1.19 - 1.18 (m, 1 H); LCMS(電灑) m/z 438.2 (M+H+). | J |
| 588 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.84 - 13.52 (m, 1H), 11.32 - 11.10 (m, 1H), 8.75 - 8.60 (m, 1H), 7.97 - 7.76 (m, 1H), 7.72 - 7.64 (m, 1H), 6.99 - 6.91 (m, 1H), 6.89 - 6.80 (m, 1H), 5.09 - 4.81 (m, 1H), 4.26 - 4.07 (m, 2H), 2.75 - 2.62 (m, 2H), 2.24 - 2.10 (m, 1H), 1.77 - 1.62 (m, 1H), 1.23 - 1.15 (m, 1H), 1.15 - 1.09 (m, 3H); LCMS(電灑) m/z 453.1 (M +H+). | J |
| 589 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.64 (s, 1 H) 11.17 (s, 1 H) 8.65 (d, J=7.2 Hz, 1 H) 8.38 (s, 1 H) 8.02 (s, 1 H) 7.37 (d, J=8.8 Hz, 1 H) 7.22 - 7.19 (m, 1 H) 6.98 (s, 1 H), 5.05 - 4.84 (m, 1 H) 2.52 (s, 3 H) 2.16 - 2.13 (m, 1 H) 1.72 - 1.64 (m, 1 H) 1.20 - 1.15 (m, 1 H); LCMS(電灑) m/z 400.1 (M+H+). | J |
| 590 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.74 (br s, 1H), 8.24 (d, J=8.3 Hz, 1H), 7.79 (s, 1H), 7.76 (d, J=11.9 Hz, 1H), 7.66 (d, J=8.3 Hz, 1H), 5.19 - 4.94 (m, 1H), 2.26 (td, J=6.9, 13.6 Hz, 1H), 1.84 - 1.70 (m, 1H), 1.39 - 1.27 (m, 1H); LCMS(電灑) m/z 440.2 (M+H+). | J |
| 591 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.55 (s, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.89 (d, J = 0.7 Hz, 1H), 7.72 - 7.41 (m, 2H), 6.95 (s, 1H), 6.89 (dd, J = 1.8, 7.0 Hz, 1H), 5.09 - 4.81 (m, 1H), 2.24 (d, J = 2.6 Hz, 3H), 2.19 - 2.11 (m, 1H), 1.76 - 1.60 (m, 1H), 1.25 - 1.11 (m, 1H); LCMS(電灑) m/z 418.1 (M+H+). | J |
| 592 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.95 ( s, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.94 ( s, 1H), 7.72 (s, 1H), 6.95 (s, 1H), 6.90 (dd, J = 1.8, 7.1 Hz, 1H), 5.11 -4.78 (m, 1H), 2.28 (d, J = 2.8 Hz, 3H), 2.20 - 2.10 (m, 1H), 1.74 - 1.61 (m, 1H), 1.24 - 1.12 (m, 1H); LCMS(電灑) m/z 452.2 (M+H+). | J |
| 593 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.43 - 13.58 (m, 1 H) 11.13 (s, 1 H) 8.62 (d, J=7.13 Hz, 1 H) 8.36 (s, 1 H) 7.94 (d, J=1.25 Hz, 1 H) 7.36 (s, 2 H) 7.17 (dd, J=7.25, 2.00 Hz, 1 H) 6.95 (s, 1 H) 4.80 - 5.07 (m, 1 H) 2.63 (s, 3 H) 2.10 - 2.18 (m, 1 H) 1.62 - 1.73 (m, 1 H) 1.17 (ddt, J=12.32, 9.04, 6.27, 6.27 Hz, 1 H); LCMS(電灑) m/z= 382.1 (M+H+). | J |
| 594 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.69 (s, 1H), 11.14 (s, 1H), 8.93 (s, 1H), 8.26-8.23 (m, 2H), 7.65 (d, J = 9.3 Hz, 1H), 7.51-7.39 (m, 1H), 5.11-4.77 (m, 1H), 4.13 (s, 3H), 2.18 (td, J = 6.8, 13.8 Hz, 1H), 1.81-1.59 (m, 1H), 1.27-1.11 (m, 1H); LCMS(電灑) m/z 470.2 (M+H+). | J |
| 595 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.26 (br s, 1H), 11.11 (s, 1H), 8.57 (br d, J = 7.1 Hz, 1H), 8.28 (s, 1H), 7.84 (s, 1H), 7.26 (br d, J = 7.7 Hz, 1H), 7.13 (dd, J = 2.0, 7.3 Hz, 1H), 6.90 (s, 1H), 6.80 (br d, J = 7.7 Hz, 1H), 5.08 - 4.79 (m, 1H), 2.93 (s, 6H), 2.14 (quin, J = 6.9 Hz, 1H), 1.74 - 1.60 (m, 1H), 1.17 (tdd, J = 6.2, 9.0, 12.3 Hz, 1H); LCMS(電灑) m/z 379.1 (M +H+). | J |
| 596 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.63 (s, 1H), 11.19 (s, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.45 (br, 1H), 7.97 (s, 1H), 7.84 (s, 1H), 6.99 (s, 1H), 6.85 (d, J = 7.2 Hz, 1H), 5.04 - 4.85 (m, 1H), 3.53 (s, 3H), 2.16 - 2.12 (m, 1H), 1.70 - 1.63 (m, 1H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 495.1 (M+H)+. | J |
| 597 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.67 (s, 1H), 11.19 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 7.82 (s, 1H), 7.69 (s, 1H), 6.94 (s, 1H), 6.85 (d, J = 7.2 Hz, 1H), 5.04 - 4.87 (m, 1H), 4.50 (q, J = 7.2 Hz, 1H), 2.69 - 2.60 (m, 2H), 4.23 (s, 2H), 2.16 - 2.12 (m, 1H), 1.70 - 1.63 (m, 1H), 1.60 (d, J = 12 Hz, 3H), 1.28 - 1.11 (m, 4H); LCMS (電灑) m/z 467.1 (M+H)+. | J |
| 598 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.15 (s, 1H), 11.17 (s, 1H), 8.63 (d, J = 7.6 Hz, 1H), 7.96 (s, 1H), 7.67 (s, 1H), 6.94 (s, 1H), 6.88 (d, J = 7.2 Hz, 1H), 5.04 - 4.87 (m, 1H), 2.30 (s, 3H), 2.15 - 2.13 (m, 1H), 1.71 - 1.64 (m, 1H), 1.24 - 1.18 (m, 1H) ; LCMS (電灑) m/z 418.10 (M+H)+. | J |
| 599 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.13 (s, 1H), 11.29 (s, 1H), 8.64 (d, J = 6.0 Hz, 1H), 7.96 (s, 1H), 7.66 (s, 1H), 6.90 - 6.88 (m, 2H), 5.00 - 4.84 (m, 1H), 2.50 - 2.43 (m, 1H), 2.30 (s, 3H), 1.58 - 1.49 (m, 1H), 1.30 - 1.24 (m, 1H) ; LCMS (電灑) m/z 418.10 (M+H)+. | J |
| 600 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.11 (s, 1H), 11.29 (s, 1H), 8.64 (d, J = 7.2 Hz, 1H), 7.96 (s, 1H), 7.66 (s, 1H), 6.90 - 6.88 (m, 2H), 5.00 - 4.84 (m, 1H), 2.50 - 2.43 (m, 1H), 2.30 (s, 3H), 1.57 (m, 1H), 1.29 - 1.24 (m, 1H) ; LCMS (電灑) m/z 418.10 (M+H)+. | J |
| 601 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.39 (s, 1H), 11.19 (s, 1H), 9.49 (s, 1H), 8.69 (d, J = 7.2 Hz, 1 H), 8.42 (d, J = 4.4 Hz, 1H), 7.91 (s, 1H), 7.83 - 7.82 (m, 1H), 6.99 - 6.97 (m, 1H), 6.86 (t, J = 5.0 Hz, 1H), 5.05 - 4.85 (m, 1H), 2.17 - 2.13 (m, 1H), 1.71 - 1.63 (m, 1H), 1.21 - 1.15 (m, 1H) ; LCMS (電灑) m/z 481.10 (M+H)+. | J |
| 602 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.63 (s, 1H), 11.21 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.05 (s, 1H), 7.85 (s, 1H), 7.00 (s, 1H), 6.98 (d, J = 7.2 Hz, 1H), 5.04 - 4.87 (m, 1H), 4.23 (s, 2H), 2.16 - 2.12 (m, 1H), 1.70 - 1.63 (m, 1H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 459.1 (M+H)+. | J |
| 603 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.65 (s, 1H), 11.19 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 7.81 (s, 1H), 7.71 (s, 1H), 6.94 (s, 1H), 6.87 (d, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 2.66 - 2.63 (m, 2H), 2.18 - 2.11 (m, 1H), 1.73 (s, 6H), 1.70 - 1.62 (m, 1H), 1.28 - 1.12 (m, 1H), 1.12 (t, J = 5.2 Hz, 3H); LCMS (電灑) m/z 481.1 (M+H)+. | J |
| 604 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.93 - 13.02 (m, 1H), 11.17 (s, 1H), 8.63 (d, J=7.2 Hz, 1H), 8.05 (s, 1H), 7.69 (d, J=1.0 Hz, 1H), 7.52 (dd, J=0.8, 9.5 Hz, 1H), 6.96 (s, 1H), 6.89 (td, J=2.2, 7.2 Hz, 1H), 5.14 - 4.72 (m, 1H), 2.85 (s, 3H), 2.72 (d, J=1.6 Hz, 3H), 2.14 (td, J=6.9, 13.8 Hz, 1H), 1.75 - 1.59 (m, 1H), 1.17 (tdd, J=6.2, 9.1, 12.3 Hz, 1H); LCMS(電灑) m/z 425.2 (M+H+). | J |
| 605 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.93 - 13.02 (m, 1H), 11.17 (s, 1H), 8.63 (d, J=7.2 Hz, 1H), 8.05 (s, 1H), 7.69 (d, J=1.0 Hz, 1H), 7.52 (dd, J=0.8, 9.5 Hz, 1H), 6.96 (s, 1H), 6.89 (td, J=2.2, 7.2 Hz, 1H), 5.14 - 4.72 (m, 1H), 2.85 (s, 3H), 2.72 (d, J=1.6 Hz, 3H), 2.14 (td, J=6.9, 13.8 Hz, 1H), 1.75 - 1.59 (m, 1H), 1.17 (tdd, J=6.2, 9.1, 12.3 Hz, 1H); LCMS(電灑) m/z 425.2 (M+H+ | J |
| 606 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.16 (s, 1H), 8.64 (br d, J = 7.1 Hz, 1H), 8.06 (s, 1H), 7.83 (s, 1H), 7.03 (br dd, J = 1.8, 7.1Hz, 1H), 6.96 (s, 1H), 5.06 - 4.82 (m, 1H), 3.86 (br d, J = 7.0 Hz, 2H), 2.55 (s, 3H), 2.18 - 2.12 (m, 1H), 1.73 - 1.61 (m, 1H), 1.26 - 1.15 (m, 1H), 1.11 (br t, J = 6.9 Hz, 3H); LCMS(電灑) m/z 444.2 (M +H+). | J |
| 607 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.06 - 13.49 (m, 1H), 10.62 (br s, 1H), 9.03 (d, J = 7.0 Hz, 1H), 8.56 (s, 1H), 8.25 (s, 1H), 7.58 (s, 1H), 7.44 (dd, J = 1.8, 7.1 Hz, 1H), 5.46 - 5.25 (m, 1H), 2.69 (br s, 1H), 2.27 - 2.21 (m, 1H), 1.69 - 1.61 (m, 1H); LCMS(電灑) m/z 472.0 (M +H+). | J |
| 608 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.64 (s, 1H), 11.19 (s, 1H), 8.67 (d, J = 7.2 Hz, 1H), 7.82 (s, 1H), 7.71 (s, 1H), 6.94 (s, 1H), 6.88 (d, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 2.66 - 2.63 (m, 2H), 2.18 - 2.11 (m, 1H), 1.73 - 7.72 (m, 2H), 1.70 - 1.62 (m, 1H), 1.62 - 1.60 (m, 1H), 1.28 - 1.12 (m, 1H), 1.12 (t, J = 5.2 Hz, 3H); LCMS (電灑) m/z 479.1 (M+H)+. | J |
| 609 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.63 (s, 1H), 11.20 (s, 1H), 8.99 (s, 1H), 8.69 (d, J = 7.2 Hz, 1H), 8.21 (d, J = 6.4 Hz, 2H), 7.99 (s, 1H), 7.83 - 7.82 (m, 1H), 7.01 - 6.98 (m, 2H), 6.62 (d, J = 4.8 Hz, 2H), 5.04 - 4.85 (m, 1H), 2.17 - 2.12 (m, 1H), 1.71 - 1.63 (m, 1H), 1.21 - 1.16 (m, 1H) ; LCMS (電灑) m/z 480.10 (M+H)+. | J |
| 610 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.28 (br s, 1H), 11.15 (s, 1H), 8.60 (d, J = 7.0 Hz, 1H), 7.96 (s, 1H), 7.77 (s, 1H), 7.01 (dd, J = 1.8, 7.3 Hz, 1H), 6.92 (s, 1H), 5.04 - 4.83 (m, 1H), 3.83 (q, J = 7.0 Hz, 2H), 2.98 (br s, 6H), 2.18 - 2.11 (m, 1H), 1.72 - 1.6 (m, 1H), 1.18 (br s, 1H), 1.11 (t, J = 7.0 Hz, 3H); LCMS(電灑) m/z 441.1 (M +H+). | J |
| 611 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.96 (s, 1H), 11.17 (s, 1H), 8.64 (d, J = 7.2 Hz, 1H), 8.18 - 8.12 (m, 1H), 7.81 (s, 1H), 7.02 - 6.93 (m, 2H), 5.04 - 4.84 (m, 1H), 3.96 - 3.82 (m, 2H), 2.18 - 2.09 (m, 1H), 1.70 - 1.60 (m, 1H), 1.20 - 1.16 (m, 1H), 1.12 (t, J = 6.8 Hz, 3H); LCMS(電灑) m/z 416.1 (M +H+). | J |
| 612 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.85 (s, 1H), 11.22 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.01 (s, 1H), 7.82 (s, 1H), 6.99 (s, 1H), 6.97 (s, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 4.72 (s, 2H), 3.03 (s, 3H), 2.18 - 2.11 (m, 1H), 1.70 - 1.62 (m, 1H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 484.1 (M+H)+. | J |
| 613 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.62 (s, 1H), 11.21 (s, 1H), 8.70 (d, J = 7.2 Hz, 1H), 8.55 (s, 1H), 7.98 (s, 1H), 7.84 (s, 1H), 7.00 - 6.99 (m, 2H), 5.03 - 4.86 (m, 1H), 3.52 (s, 3H), 2.17 - 2.12 (m, 1H), 1.71 - 1.64 (m, 1H), 1.21 - 1.14 (m, 1H) ; LCMS (電灑) m/z 513.10 (M+H)+. | J |
| 614 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.75 (s, 1H), 11.20 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.22 (d, J = 6.8 Hz, 1H), 8.04 (s, 1H), 7.84 (s, 1H), 7.01 (dd, J = 2.2, 7.0 Hz, 2H), 6.60 (d, J = 5.6 Hz, 1H), 5.06 - 4.86 (m, 1H), 3.41 (s, 3H), 2.19 - 2.12 (m, 1H), 1.73 - 1.63 (m, 1H), 1.21 - 1.17 (m, 1H) ; LCMS (電灑) m/z 494.10 (M+H)+. | J |
| 615 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.02 (s, 1H), 11.21 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.09 (s, 1H), 7.83 (s, 1H), 7.00 (s, 1H), 6.97 (s, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 4.79 (dd, J = 18 Hz, 110 Hz, 2H), 2.18 - 2.11 (m, 1H), 1.90 (s, 3H), 1.70 - 1.62 (m, 1H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 484.1 (M+H)+. | J |
| 616 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.51 (s, 1H), 11.19 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 8.38 (dd, J = 1.6, 4.4 Hz, 2H), 7.89 (s, 1H), 7.73 - 7.72 (m, 1H), 7.21 (d, J = 6.0 Hz, 2H), 6.95 (s, 1H), 6.90 (dd, J = 2.4, 7.2 Hz, 1H), 5.05 - 4.84 (m, 1H), 3.54 (t, 2H), 3.06 (d, J = 2.0 Hz, 3H), 2.86 (t, J = 7.4 Hz, 2H), 2.18 - 2.11 (m, 1H), 1.72 - 1.64 (m, 1H), 1.21 - 1.13 (m, 1H) ; LCMS (電灑) m/z 522.10 (M+H)+. | J |
| 617 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.70 (s, 1H), 11.21 (s, 1H), 8.91 (d, J = 0.8 Hz, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.58 (d, J = 2.0 Hz, 1H), 8.01 (s, 1H), 7.85 (s, 1H), 7.01 - 6.99 (m, 2H), 5.04 - 4.85 (m, 1H), 3.55 (s, 3H), 2.18 - 2.11 (m, 1H), 1.71 - 1.64 (m, 1H), 1.21 - 1.14 (m, 1H) ; LCMS (電灑) m/z 496.10 (M+H)+. | J |
| 618 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.67 (s, 1H), 11.21 (s, 1H), 8.88 (d, J = 2.0 Hz, 1H), 8.71 (d, J = 7.2 Hz, 1H), 8.38 (s, 1H), 8.01 (s, 1H), 7.85 (s, 1H), 7.01 - 6.99 (m, 2H), 5.05 - 4.84 (m, 1H), 3.63 (s, 3H), 2.18 - 2.11 (m, 1H), 1.71 - 1.63 (m, 1H), 1.21 - 1.11 (m, 1H) ; LCMS (電灑) m/z 496.10 (M+H)+. | J |
| 619 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.29 (s, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.3 Hz, 1H), 7.87 (s, 1H), 7.71 (s, 1H), 6.92 - 6.90 (m, 2H), 5.18 - 5.17 (m, 1H), 5.03 - 4.85 (m, 1H), 4.03 (s, 1H), 2.17 - 2.09 (m, 1H), 1.72 - 1.62 (m, 1H), 1.23 (d, J = 6.4 Hz, 6H), 1.20 - 1.15 (m, 1H) ; LCMS (電灑) m/z 445.10 (M+H)+. | J |
| 620 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.51 (s, 1H), 11.19 (s, 1H), 8.65 (d, J = 7.2 Hz, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 6.94 (s, 1H), 6.92 (s, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 3.93 (t, J = 9.6 Hz, 1H), 2.84 (s, 3H), 2.18 - 2.07 (m, 3H), 1.96 - 1.86 (m, 2H), 1.72 - 1.57 (m, 3H), 1.28 - 1.12 (m, 1H); LCMS (電灑) m/z 471.1 (M+H)+. | J |
| 621 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.81 (s, 1H), 11.21 (s, 1H), 8.69 (d, J = 7.2 Hz, 1H), 7.88 (s, 1H), 7.81 (s, 1H), 6.97 (s, 1H), 6.95 (s, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 3.02 (q, J = 7.3 Hz, 2H), 2.18 - 2.08 (m, 1H), 1.72 - 1.62 (m, 1H), 1.22 - 1.13 (m, 4H); LCMS (電灑) m/z 448.1 (M+H)+. | J |
| 622 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (s, 1H), 11.20 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.89 (s, 1H), 7.76 (d, J = 1.2 Hz, 1H), 6.95 - 6.93 (m, 2H), 5.03 - 4.84 (m, 1H), 3.56 (s, 1H), 2.89 (d, J = 3.6 Hz, 3H), 2.18 - 2.11 (m, 1H), 1.72 - 1.62 (m, 1H), 1.22 - 1.15 (m, 7H) ; LCMS (電灑) m/z 459.10 (M+H)+. | J |
| 623 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.66 (s, 1H), 11.21 (s, 1H), 8.70 (d, J = 7.2 Hz, 1H), 7.97 (s, 1H), 7.80 (m, 1H), 6.97 - 6.94 (m, 2H), 5.05 - 4.85 (m, 1H), 3.84 (t, J = 7.8 Hz, 2H), 3.60 (t, J = 8.0 Hz, 2H), 2.82 (s, 3H), 2.18 - 2.11 (m, 1H), 1.73 - 1.62 (m, 1H), 1.21 - 1.15 (m, 1H) ; LCMS (電灑) m/z 486.10 (M+H)+. | J |
| 624 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.13 (s, 1H), 11.17 (s, 1H), 8.62 (d, J = 6.8 Hz, 1H), 7.86 (s, 1H), 7.69 (d, J = 0.8 Hz, 1H), 6.96 - 6.86 (m, 2H), 5.05 - 4.83 (m, 1H), 4.68 - 4.58 (m, 2H), 4.37 - 4.30 (m, 1H), 4.27 - 4.16 (m, 2H), 3.27 (s, 3H), 2.18 - 2.09 (m, 1H), 1.73 - 1.61 (m, 1H), 1.20 - 1.12 (m, 1H); LCMS (電灑) m/z 473.1 (M+H)+. | J |
| 625 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.41 (s, 1H), 11.19 (s, 1H), 8.65 (d, J = 7.2 Hz, 1H), 7.87 (s, 1H), 7.76 (s, 1H), 6.94 (s, 1H), 6.92 (s, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 3.01 - 2.98 (m, 4H), 2.18 - 2.08 (m, 1H), 1.72 - 1.62 (m, 1H), 1.22 - 1.13 (m, 4H), 0.63 - 0.60 (m, 2H), 0.49 - 0.45 (m, 2H); LCMS (電灑) m/z 457.1 (M+H)+. | J |
| 626 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.02 (s, 1H), 11.24 (s, 1H), 10.49 (s, 1H), 8.73 (d, J = 7.2 Hz, 1H), 8.07 (s, 1H), 7.89-7.87 (m, 1H), 7.02 (s, 1H), 7.00 (dd, J = 7.0, 1.8 Hz, 1H), 5.06-4.85 (m, 1H), 2.19-2.12 (m, 1H), 1.73-1.63 (m, 1H), 1.21-1.15 (m, 1H); LCMS (電灑) m/z 416.05 (M+H+). | J |
| 627 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.06 (s, 1H), 11.13 (s, 1H), 8.58 (d, J = 6.8 Hz, 1H), 7.81 (s, 1H), 7.64 (s, 1H), 6.90 - 6.81 (m, 2H), 5.02 - 4.80 (m, 1H), 4.49 - 4.40 (m, 2H), 4.20 - 4.04 (m, 2H), 3.53 (d, J = 6.4 Hz, 2H), 3.25 (s, 3H), 2.99 - 2.88 (m, 1H), 2.15 - 2.04 (m, 1H), 1.68 - 1.57 (m, 1H), 1.17 - 1.09 (m, 1H); LCMS (電灑) m/z 487.1 (M+H)+. | J |
| 628 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.62 (s, 1H), 11.20 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 7.95 (d, J = 2.0 Hz, 1H), 7.74 (d, J = 1.2 Hz, 1H), 6.96 (s, 1H), 6.91 (dd, J = 1.6, 7.2 Hz, 1H), 5.06 - 4.84 (m, 1H), 3.69 - 3.61 (m, 4H), 3.47 - 3.39 (m, 4H), 2.18 - 2.10 (m, 1H), 1.73 - 1.61 (m, 1H), 1.21 - 1.12 (m, 1H); LCMS (電灑) m/z 521.1 (M+H)+. | J |
| 629 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.57 (s, 1H), 11.20 (s, 1H), 10.49 (s, 1H), 8.68 (d, J = 7.2 Hz, 1H), 8.07 (s, 1H), 7.89-7.87 (m, 1H), 7.02 (s, 1H), 7.00 (dd, J = 7.0, 1.8 Hz, 1H), 5.06-4.85 (m, 1H), 2.19-2.12 (m, 1H), 1.73-1.63 (m, 1H), 1.21-1.15 (m, 1H); LCMS (電灑) m/z 416.05 (M+H+). | J |
| 630 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.41 (s, 1H), 11.19 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.91 (s, 1H), 7.76 (s, 1H), 6.94 (s, 1H), 6.87 (s, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 4.55 - 4.51 (m, 2H), 3.98 - 3.94 (m, 2H), 2.85 - 2.80 (m, 1H), 2.15 - 2.08 (m, 1H), 1.72 - 1.62 (m, 1H), 1.29 - 1.12 (m, 4H), 0.86 - 0.79 (m, 1H); LCMS (電灑) m/z 457.1 (M+H)+. | J |
| 631 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.49 (s, 1H), 11.19 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.91 (s, 1H), 7.74 (t, J = 1.2 Hz, 1H), 6.95 (s, 1H), 6.91 (dd, J = 2.4, 7.2 Hz, 1H), 5.06 - 4.84 (m, 1H), 3.53 - 3.39 (m, 4H), 2.90 - 2.82 (m, 4H), 2.19 - 2.09 (m, 1H), 1.73 - 1.61 (m, 1H), 1.21 - 1.12 (m, 1H); LCMS (電灑) m/z 489.1 (M+H)+. | J |
| 632 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.41 (s, 1H), 11.20 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.96 (s, 1H), 7.68 (s, 1H), 6.92 (s, 1H), 6.87 (s, J = 7.2 Hz, 1H), 5.04 - 4.84 (m, 1H), 4.55 - 4.44 (m, 4H), 2.15 - 2.08 (m, 1H), 1.72 - 1.62 (m, 1H), 1.66 (d, J = 22 Hz, 1H), 1.29 - 1.12 (m, 1H); LCMS (電灑) m/z 475.1 (M+H)+. | J |
| 633 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.90 (br s, 1H), 11.23 (s, 1H), 8.71 (d, J = 7.2 Hz, 1H), 7.99 (d, J = 17.2 Hz, 1H), 7.85-7.83 (m, 1H), 7.00 (s, 1H), 6.97 (dd, J = 7.0, 2.0 Hz, 1H), 5.06-4.85 (m, 1H), 2.18-2.11 (m, 1H), 1.73-1.63 (m, 1H), 1.21-1.14 (m, 1H); LCMS (電灑) m/z 439.05 (M+H+). | J |
| 634 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.91 (s, 1H), 11.22 (s, 1H), 8.70 (d, J = 7.2 Hz, 1H), 7.99 (s, 1H), 7.83-7.80 (m, 1H), 6.98 (s, 1H), 6.96 (dd, J = 7.0, 1.8 Hz, 1H), 5.93 (s, 1H), 5.81 (s, 1H), 5.05-4.84 (m, 1H), 2.18-2.11 (m, 1H), 1.72-1.62 (m, 1H), 1.20-1.13 (m, 1H); LCMS (電灑) m/z 420.00 (M+H+). | J |
| 635 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.59 (s, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.93 (s, 1H), 7.75 (t, J = 1.4 Hz, 1H), 6.96 (s, 1H), 6.92 (dd, J = 7.1, 1.6 Hz, 1H), 5.08-4.80 (m, 1H), 3.89 (t, J = 11.5 Hz, 2H), 3.32-3.24 (m, 2H), 3.24-3.10 (m, 2H), 2.97 (d, J = 11.5 Hz, 2H), 2.22-2.09 (m, 1H), 1.77-1.61 (m, 1H), 1.22-1.11 (m, 1H); LCMS (電灑) m/z 505.10 (M+H)+. | J |
| 636 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.44 (s, 1H), 11.18 (s, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.75 (s, 1H), 7.03-6.84 (m, 2H), 6.42 (s, 1H), 5.10-4.83 (m, 1H), 4.83-4.49 (m, 2H), 2.24-2.04 (m, 1H), 1.76-1.59 (m, 1H), 1.21-1.05 (m, 1H); LCMS (電灑) m/z 442.10 (M+H)+. | J |
| 637 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.63-14.10 (1H), 11.21 (s, 1H), 8.71 (d, J = 7.1 Hz, 1H), 8.09 (s, 1H), 7.82 (t, J = 1.4 Hz, 1H), 7.28 (s, 2H), 6.99 - 6.96 (m, 2H), 6.41 (t, J = 2.2 Hz, 2H), 5.06 - 4.85 (m, 1H), 2.19 - 2.12 (m, 1H), 1.73 - 1.63 (m, 1H), 1.21 - 1.14 (m, 1H); LCMS (電灑) m/z 453.10 (M+H)+. | J |
| 638 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.51 (s, 1H), 11.20 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.92 (s, 1H), 7.80 (d, J = 1.1 Hz, 1H), 7.02-6.87 (m, 2H), 5.76 (s, 1H), 5.09-4.81 (m, 1H), 2.23-2.07 (m, 1H), 1.75-1.61 (m, 7H), 1.21-1.10 (m, 2H); LCMS (電灑) m/z 470.10 (M+H)+. | J |
| 639 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.67 - 13.30 (m, 1H), 11.18 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.94 (s, 1H), 7.79 (d, J = 1.0 Hz, 1H), 7.05 - 6.79 (m, 2H), 5.63 (s, 1H), 5.38 (s, 1H), 5.15 - 4.77 (m, 1H), 2.21 (s, 3H), 2.18 - 2.09 (m, 1H), 1.74 - 1.60 (m, 1H), 1.25 - 1.12 (m, 1H); LCMS (電灑) m/z 428.1 (M+H+). | J |
| 640 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.61 (br d, J = 2.1 Hz, 1H), 11.18 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.92 (s, 1H), 7.76 (d, J = 0.9 Hz, 1H), 7.07 - 6.84 (m, 2H), 5.10 - 4.76 (m, 1H), 3.62 (td, J = 7.0, 14.1 Hz, 1H), 2.15 (td, J = 6.9, 13.8 Hz, 1H), 1.76 - 1.59 (m, 1H), 1.44 (d, J = 7.0 Hz, 6H), 1.18 (tdd, J = 6.2, 9.0, 12.3 Hz, 1H); LCMS (電灑) m/z 430.2 (M+H+). | J |
| 641 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.32 (s, 1H), 11.03 (s, 1H), 8.61 (d, J = 7.1 Hz, 1H), 7.95 (s, 1H), 7.73 (s, 1H), 6.98-6.88 (m, 2H), 6.24-5.96 (m, 1H), 5.05-4.81 (m, 1H), 3.34-3.24 (m, 1H), 2.22-2.09 (m, 1H), 1.78-1.58 (m, 4H), 1.22-1.11 (m, 1H); LCMS (電灑) m/z 456.10 (M+H)+. | J |
| 642 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.11 (s, 1H), 10.83 (s, 1H), 8.54 (d, J = 7.1 Hz, 1H), 7.90-7.72 (m, 1H), 7.62 (s, 1H), 6.88 (s, 1H), 6.86-6.79 (m, 1H), 5.56-5.24 (m, 1H), 5.00-4.74 (m, 1H), 4.34-3.50 (m, 4H), 2.38-2.03 (m, 3H), 1.75-1.56 (m, 1H), 1.19-1.04 (m, 1H); LCMS (電灑) m/z 475.10 (M+H)+. | J |
| 643 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.83 (s, 1H), 11.08 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.99 (s, 1H), 7.82 (d, J = 5.5 Hz, 1H), 7.67-6.83 (m, 7H), 5.59-5.07 (m, 3H), 5.05-4.79 (m, 1H), 2.23-2.09 (m, 1H), 1.79-1.62 (m, 2H), 1.43 (d, J = 7.1 Hz, 2H), 1.23-1.09 (m, 1H); LCMS (電灑) m/z 591.20 (M+H)+. | J |
| 644 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.21 (s, 1H), 8.72 (d, J=7.2 Hz, 1H), 8.07 (s, 1H), 7.87 (d, J=1.0 Hz, 1H), 7.05 - 6.99 (m, 2H), 6.95 (br s, 1H), 6.27 (t, J=3.2 Hz, 1H), 6.16 - 6.11 (m, 1H), 5.08 - 4.84 (m, 1H), 2.16 (td, J=6.8, 14.1 Hz, 1H), 2.10 - 2.04 (m, 3H), 1.78 - 1.63 (m, 1H), 1.23 - 1.15 (m, 1H); LCMS (電灑) m/z 467.1 (M +H+). | J |
| 645 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.95 - 13.76 (m, 1H), 10.54 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 8.47 ( s, 1H), 7.98 (s, 1H), 7.76 (d, J = 1.0 Hz, 1H), 6.91 (dd, J = 2.0, 7.1 Hz, 1H), 6.76 (s, 1H), 4.92 - 4.85 (m, 1H), 4.03 - 3.91 (m, 2H), 3.76 (dd, J = 1.3, 10.6 Hz, 1H), 2.57 (s, 3H), 2.38 - 2.29 (m, 1H), 1.06 (d, J = 7.2 Hz, 3H); LCMS (電灑) m/z 476.1(M+H+). | J |
| 646 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.51 (s, 1H), 11.07 (s, 1H), 9.60-9.58 (m, 1H), 8.64 (d, J = 7.1 Hz, 1H), 7.87 (s, 1H), 7.72 (s, 1H), 7.53 (s, 1H), 7.28 (s, 1H), 6.94 (s, 1H), 6.90 (dd , J=7.1, 1.8 Hz, 1H), 3.80 (s, 3H), 2.99 (7H), 2.32 (dd, J=9.1, 4.3 Hz, 2H), 2.00-1.95 (m, 1H), 1.68-1.55 (m, 1H), 1.37-1.18 (m, 2H), 0.97 (d, J=6.2 Hz, 3H); LCMS (電灑) m/z 507.1 (M+H)+. | J |
| 647 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.52 (s, 1H), 9.05 (s, 1H), 8.57 (d, J = 7.0 Hz, 1H), 7.87 (s, 1H), 7.65 (dd , J=1.77, 0.79 Hz, 1H), 6.85-6.81 (m, 2H), 6.72 (s, 1H), 3.01 (s, 6H), 2.62-2.58 (m, 1H), 0.69-0.65 (m, 2H), 0.46-0.44 (m, 2H); LCMS (電灑) m/z 428.0 (M+H)+. | J |
| 648 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.03 (s, 1H), 8.63 (d, J = 7.2 Hz, 1H), 8.55 (s, 1H), 7.87 (s, 1H), 7.71 (s, 1H), 7.53 (s, 1H), 7.26 (s, 1H), 6.97 (s, 1H), 6.90 (dd , J=7.1, 1.8 Hz, 1H), 3.77 (s, 3H), 3.02 (d, J=2.2 Hz, 6H), 2.22-2.14 (m, 1H), 2.09 (d, J=4.5 Hz, 3 H), 1.63-1.54 (m, 1H), 1.26 (d, J=6.1 Hz, 5H), 1.06 (t, J=7.0 Hz, 2H); LCMS (電灑) m/z 507.1 (M+H)+. | J |
| 649 |  | 1H NMR (400 MHz, DMSO-d 6) δ 11.20 (s, 1H), 8.71 (d, J = 7.1 Hz, 1H), 8.13 (s, 1H), 7.84-7.80 (m,1H), 7.50-7.38 (m, 1H), 7.00 (s, 1H), 6.97 (dd , J=7.19, 1.94 Hz, 1 H), 6.66 (dd, J=2.94, 1.69 Hz, 1 H), 5.09 - 4.81 (m, 1H), 3.15-2.95 (m, 5H), 2.20-2.11 (m, 1H), 1.75-1.61 (m, 1H), 1.22-1.12 (m, 1H); LCMS (電灑) m/z 524.1 (M+H)+. | J |
| 650 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.17 - 13.20 (m, 1H), 11.17 (s, 1H), 8.66 (d, J = 7.2 Hz, 1H), 7.94 (s, 1H), 7.76 (s, 1H), 7.00 - 6.89 (m, 2H), 5.10 - 4.80 (m, 1H), 4.74 (br s, 1H), 2.15 (quin, J = 6.9 Hz, 1H), 1.77 - 1.59 (m, 1H), 1.37 (d, J = 6.0 Hz, 6H), 1.26 - 1.09 (m, 1H); LCMS (電灑) m/z 446.0 (M+H)+. | J |
| 651 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.55 (s, 1H), 11.19 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.90 (d, J = 1.1 Hz, 1H), 7.76 (t, J = 1.1 Hz, 1H), 6.96-6.92 (m, 2H), 5.05-4.84 (m, 1H), 3.59 (q, J = 8.6 Hz, 1H), 2.18-1.91 (m, 8H), 1.72-1.62 (m, 3H), 1.24-1.06 (m, 1H); LCMS (電灑) m/z 456.1 (M+H)+. | J |
| 652 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.35 (s, 1H), 11.15 (s, 1H), 8.65 (d, J = 7.1 Hz, 1H), 7.90 (s, 1H), 7.79 (t, J = 1.4 Hz, 1H), 7.59 (s, 1H), 6.93 (dd, J = 6.3, 2.5 Hz, 2H), 5.74 (t, J = 7.4 Hz, 1H), 5.01-4.80 (m, 1H), 2.15-2.08 (m, 1H), 1.64 (dtd, J = 23.2, 6.9, 3.8 Hz, 1H), 1.17-1.10 (m, 1H); LCMS (電灑) m/z 487.1 (M+H)+. | J |
| 653 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.25 (br s, 1H), 11.14 (s, 1H), 8.61 (d, J = 7.2 Hz, 1H), 7.85 (br s, 1H), 7.70 (s, 1H), 6.92 (s, 1H), 6.91 - 6.88 (m, 1H), 5.32 (br d, J = 9.5 Hz, 1H), 5.06 - 4.82 (m, 1H), 2.21 - 2.06 (m, 1H), 1.75 - 1.61 (m, 1H), 1.26 (d, J = 6.4 Hz, 3H), 1.21 - 1.14 (m, 1H), 1.04 (br s, 1H), 0.48 - 0.35 (m, 2H), 0.34 - 0.18 (m, 2H); LCMS (電灑) m/z 471.1 (M+H)+. | J |
| 654 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.26 (s, 1H), 11.15 (s, 1H), 8.61 (d, J = 7.0 Hz, 1H), 7.85 (m, 1H), 7.70 (d, J = 1.0 Hz, 1H), 6.91 (m, 2H), 5.65 (m, 1H), 4.95 (m, 1H), 3.31 (s, 2H), 2.14 (m, 1H), 1.67 (m, 1H), 1.18 (m, 1H), 1.08 (m ,1H), 0.48 (d, J = 7.1 Hz, 2H), 0.27 (m, 2H); LCMS (電灑) m/z 457.1 (M+H)+. | J |
| 655 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.56 (br s, 1H), 11.17 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.91 (s, 1H), 7.78 (s, 1H), 6.96 (br d, J = 2.2 Hz, 1H), 6.95 - 6.91 (m, 1H), 5.07 - 4.82 (m, 1H), 3.85 - 3.74 (m, 2H), 3.67 (br s, 1H), 3.25 (s, 3H), 2.21 - 2.09 (m, 1H), 1.74 - 1.60 (m, 1H), 1.40 (br d, J = 6.1 Hz, 3H), 1.22 - 1.12 (m, 1H); LCMS (電灑) m/z 460.1 (M+H)+. | J |
| 656 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.56 (br s, 1H), 11.17 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.91 (s, 1H), 7.78 (d, J = 1.0 Hz, 1H), 6.96 (d, J = 2.6 Hz, 1H), 6.95 - 6.92 (m, 1H), 5.07 - 4.79 (m, 1H), 3.85 - 3.73 (m, 2H), 3.67 (br s, 1H), 3.25 (s, 3H), 2.15 (td, J = 6.8, 13.7 Hz, 1H), 1.73 - 1.61 (m, 1H), 1.40 (br d, J = 6.2 Hz, 3H), 1.18 (ddd, J = 2.8, 6.2, 12.3 Hz, 1H); LCMS (電灑) m/z 460.1 (M+H)+. | J |
| 657 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (s, 1H), 11.15 (s, 1H), 8.62 (d, J = 7.1 Hz, 1H), 8.04-7.83 (m, 1H), 7.71 (d, J = 1.0 Hz, 1H), 6.92 (s, 1H), 6.90 (dd, J = 7.1, 2.0 Hz, 1H), 6.33-5.92 (m, 1H), 5.67-5.51 (m, 1H), 5.07-4.81 (m, 1H), 4.53-4.03 (m, 1H), 2.21-2.05 (m, 1H), 1.75-1.57 (m, 1H), 1.32 (d, J = 6.6 Hz, 3H), 1.17 (ddt, J=12.26, 9.07, 6.16, 6.16 Hz, 1 H); LCMS (電灑) m/z 481.0 (M+H)+. | J |
| 658 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.15 (s, 1H), 11.19 (s, 1H), 8.68 (d, J = 7.1 Hz, 1H), 7.92 (s, 1H), 7.78 (d, J = 1.0 Hz, 1H), 6.98 (s, 1H), 6.94 (dd, J = 2.0, 7.1 Hz, 1H), 5.57 (dd, J = 5.4, 10.8 Hz, 1H), 5.18 (d, J = 3.4 Hz, 1H), 5.07 - 4.83 (m, 1H), 4.55 (dd, J = 3.7 Hz, 1H), 4.47 (dd, J = 4.6, 8.9 Hz, 1H), 3.72 (dd, J = 1.2, 9.0 Hz, 1H), 2.26 (dd, J = 5.4, 12.5 Hz, 1H), 2.20 - 2.02 (m, 2H), 1.76 - 1.62 (m, 1H), 1.28 - 1.12 (m, 2H); LCMS (電灑) m/z 474.2 (M+H)+. | J |
| 659 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.80 - 13.56 (m, 1H), 11.18 (s, 1H), 8.77 (br d, J = 6.6 Hz, 1H), 8.67 (d, J = 7.1 Hz, 1H), 8.06 (s, 1H), 7.94 (s, 1H), 7.77 (d, J = 0.9 Hz, 1H), 6.96 (s, 1H), 6.93 (dd, J = 1.8, 7.2 Hz, 1H), 5.56 (br t, J = 7.2 Hz, 1H), 5.11 - 4.78 (m, 1H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.73 - 1.62 (m, 1H), 1.58 (d, J = 7.2 Hz, 3H), 1.18 (tdd, J = 6.4, 9.0, 12.4 Hz, 1H); LCMS (電灑) m/z 459.2 (M+H)+. | J |
| 660 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.73 - 13.44 (m, 1H), 11.17 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 8.46 - 8.32 (m, 1H), 7.92 (s, 1H), 7.77 (s, 1H), 6.96 (s, 1H), 6.93 (dd, J = 2.0, 7.2 Hz, 1H), 5.46 (br t, J = 7.0 Hz, 1H), 5.09 - 4.77 (m, 1H), 2.20 - 2.07 (m, 3H), 1.78 - 1.61 (m, 1H), 1.55 (br d, J = 7.2 Hz, 3H), 1.27 - 1.07 (m, 1H), 0.95 (t, J = 7.6 Hz, 3H); LCMS (電灑) m/z 487.2 (M+H)+. | J |
| 661 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.77 - 13.42 (m, 1H), 11.18 (s, 1H), 8.67 (d, J = 7.1 Hz, 1H), 8.54 - 8.48 (m, 1H), 8.34 (br s, 1H), 7.91 (s, 1H), 7.77 (d, J = 0.7 Hz, 1H), 6.95 (s, 1H), 6.93 (dd, J = 2.0, 7.2 Hz, 1H), 5.45 (br t, J = 7.1 Hz, 1H), 5.05 - 4.83 (m, 1H), 3.08 (br t, J = 8.3 Hz, 1H), 2.19 - 2.01 (m, 3H), 1.99 - 1.83 (m, 3H), 1.75 - 1.61 (m, 2H), 1.55 (d, J = 7.2 Hz, 3H), 1.17 (ddd, J = 2.8, 6.1, 12.3 Hz, 1H); LCMS (電灑) m/z 513.2 (M+H)+. | J |
| 662 |  | 1H NMR (400 MHz, DMSO-d 6) δ14.24-12.89 (m, 1H), 11.19 (s, 1H), 10.54-9.82 (m, 1H), 8.68 (d, J = 7.0 Hz, 1H), 7.97 (s, 1H), 7.00-6.92 (m, 2H), 5.56 (q, J = 7.0 Hz, 1H), 5.07- 4.81 (m, 1H), 2.21-2.08 (m, 1H), 1.69 (d, J = 7.0 Hz, 3H), 1.66 - 1.60 (m, 1H), 1.26-1.09 (m, 1H); LCMS (電灑) m/z 527.1 (M+H)+. | J |
| 663 |  | 1H NMR (400 MHz, DMSO-d 6) δ13.90-13.44 (m, 1H), 11.21-11.13 (m, 1H), 8.94-8.80 (m, 1H), 8.66 (d, J = 7.2 Hz, 1H), 8.56 (s, 1H), 7.96-7.86 (m, 1H), 7.80-7.73 (m, 1H), 6.95 (s, 1H), 6.94-6.91 (m, 1H), 5.54-5.41 (m, 1H), 4.93 (s, 1H), 2.22-2.09 (m, 1H), 1.90-1.82 (m, 3H), 1.73-1.61 (m, 1H), 1.54 (d, J = 7.0 Hz, 3H), 1.21 - 1.13 (m, 1H); LCMS (電灑) m/z 473.1 (M+H)+. | J |
| 664 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.73 (s, 1H), 11.21 (s, 1H), 8.70 (d, J = 7.1 Hz, 1H), 7.97 (s, 1H), 7.77 (s, 1H), 7.00 (s, 1H), 6.93 (dd, J = 7.1, 2.2 Hz, 1H), 6.40 (s, 1H), 5.05-4.85 (m, 1H), 3.20 (s, 3H), 2.58 (d, J = 4.4 Hz, 3H), 2.18-2.11 (m, 1H), 1.72-1.64 (m, 1H), 1.21-1.15 (m, 1H) m/z 474.10 (M+H)+. | J |
| 665 |  | 1H NMR (400 MHz, DMSO-d 6) δ 14.06 - 13.53 (m, 1H), 11.18 (s, 1H), 9.82 - 9.45 (m, 1H), 8.67 (d, J = 7.1 Hz, 1H), 7.95 (s, 1H), 7.78 (d, J = 0.9 Hz, 1H), 6.99 - 6.91 (m, 2H), 6.44 - 6.11 (m, 1H), 5.61 - 5.51 (m, 1H), 5.05 - 4.83 (m, 1H), 2.15 (td, J = 7.0, 13.8 Hz, 1H), 1.70 (dt, J = 3.7, 6.9 Hz, 1H), 1.65 (d, J = 7.2 Hz, 3H), 1.24 - 1.12 (m, 1H); LCMS (電灑) m/z 509.2 (M+H)+. | J |
| 666 |  | 1H NMR (400 MHz, DMSO-d 6) δ 13.33 (s, 1H), 11.20 (s, 1H), 8.67 (t, J = 8.0 Hz, 1H), 7.91 (s, 1H), 7.82 (t, J = 1.1 Hz, 1H), 6.97 (dd, J = 7.1, 2.2 Hz, 2H), 5.04-4.85 (m, 2H), 3.90 (t, J = 6.3 Hz, 1H), 3.38 (d, J = 6.6 Hz, 3H), 3.25 (s, 3H), 2.14 (t, J = 8.0 Hz, 1H), 1.71-1.64 (m, 1H), 1.18 (dd, J = 12.1, 8.8 Hz, 1H), 0.95 (d, J = 6.6 Hz, 3H); LCMS (電灑) m/z 490.1 (M+H)+. | J |
化合物的評價
HPK1激酶試驗
藉由Promega的ADP Glo™ 激酶試驗測定HPK1激酶活性。在測定過程中，將5 ng重組人類HPK1（signalchem）與5μL化合物（0.5%DMSO）、5μL MBP（0.5µg/µL）和5μL ATP（25µM）在緩衝液（40mM Tris，7.5；20mM MgCl
2；0.1mg/ml BSA；50μM DTT）中一起培養。於檢測開始，將反應混合物在96孔盤中於30℃下培養40分鐘。培養後，加入25uL ADP-Glo試劑，並在室溫下培養作用40分鐘以停止反應並降解殘餘的ATP。接著透過在每孔中加入50uL的檢測試劑將ADP產物轉化為ATP。在室溫下培養30分鐘後，用Molecular device I3X讀盤儀檢測冷光。使用在GraphPad Prism 7軟體或SigmaPlot 13.0中執行的軟體程序，從抑制劑濃度範圍中選定的一系列抑制百分比值計算出IC
50值
表2示出本發明化合物之IC
50值，其中+表示＞1000nM，++表示501-1000nM，+++表示101-500nM，++++表示＜100nM。
表2 針對HPK1數據的體外活性
| 實施例 | HPK1 IC 50(nM) | 實施例 | HPK1 IC 50(nM) | 實施例 | HPK1 IC 50(nM) |
| 1 | +++ | 45 | + | 89 | ++++ |
| 2 | +++ | 46 | ++++ | 90 | ++++ |
| 3 | + | 47 | ++++ | 91 | +++ |
| 4 | ++ | 48 | ++++ | 92 | ++++ |
| 5 | +++ | 49 | ++ | 93 | ++++ |
| 6 | +++ | 50 | ++++ | 94 | ++++ |
| 7 | +++ | 51 | ++++ | 95 | ++++ |
| 8 | + | 52 | + | 96 | ++++ |
| 9 | + | 53 | +++ | 97 | ++++ |
| 10 | + | 54 | + | 98 | ++++ |
| 11 | ++ | 55 | +++ | 99 | ++++ |
| 12 | + | 56 | ++++ | 100 | ++++ |
| 13 | + | 57 | ++++ | 101 | ++++ |
| 14 | + | 58 | ++++ | 102 | ++++ |
| 15 | +++ | 59 | ++++ | 103 | ++++ |
| 16 | +++ | 60 | + | 104 | ++++ |
| 17 | +++ | 61 | ++++ | 105 | ++++ |
| 18 | + | 62 | +++ | 106 | ++++ |
| 19 | + | 63 | ++++ | 107 | ++++ |
| 20 | + | 64 | ++++ | 108 | ++++ |
| 21 | + | 65 | ++++ | 109 | ++++ |
| 22 | + | 66 | ++++ | 110 | ++++ |
| 23 | + | 67 | ++++ | 111 | ++++ |
| 24 | +++ | 68 | ++++ | 112 | +++ |
| 25 | ++ | 69 | ++++ | 113 | ++++ |
| 26 | + | 70 | ++++ | 114 | +++ |
| 27 | + | 71 | ++++ | 115 | ++++ |
| 28 | +++ | 72 | +++ | 116 | ++++ |
| 29 | +++ | 73 | ++++ | 117 | ++++ |
| 30 | +++ | 74 | +++ | 118 | ++++ |
| 31 | + | 75 | +++ | 119 | +++ |
| 32 | +++ | 76 | +++ | 120 | ++++ |
| 33 | +++ | 77 | ++++ | 121 | + |
| 34 | + | 78 | +++ | 122 | ++++ |
| 35 | +++ | 79 | ++++ | 123 | ++++ |
| 36 | +++ | 80 | ++++ | 124 | + |
| 37 | +++ | 81 | ++++ | 125 | ++++ |
| 38 | + | 82 | ++++ | 126 | ++++ |
| 39 | +++ | 83 | +++ | 127 | ++++ |
| 40 | ++++ | 84 | ++++ | 128 | +++ |
| 41 | +++ | 85 | ++++ | 129 | ++++ |
| 42 | +++ | 86 | ++++ | 130 | ++++ |
| 43 | ++++ | 87 | ++++ | 131 | +++ |
| 44 | ++ | 88 | ++++ | 132 | +++ |
| 133 | ++++ | 179 | ++++ | 225 | + |
| 134 | ++++ | 180 | +++ | 226 | ++++ |
| 135 | + | 181 | +++ | 227 | + |
| 136 | ++++ | 182 | + | 228 | + |
| 137 | ++++ | 183 | ++++ | 229 | ++++ |
| 138 | ++++ | 184 | ++++ | 230 | + |
| 139 | ++++ | 185 | +++ | 231 | + |
| 140 | + | 186 | ++++ | 232 | ++++ |
| 141 | + | 187 | ++++ | 233 | ++ |
| 142 | + | 188 | + | 234 | + |
| 143 | ++++ | 189 | ++++ | 235 | ++++ |
| 144 | +++ | 190 | ++++ | 236 | ++++ |
| 145 | + | 191 | ++++ | 237 | ++++ |
| 146 | +++ | 192 | ++++ | 238 | ++++ |
| 147 | ++++ | 193 | ++++ | 239 | ++++ |
| 148 | + | 194 | ++++ | 240 | ++ |
| 149 | ++++ | 195 | +++ | 241 | + |
| 150 | ++++ | 196 | ++++ | 242 | +++ |
| 151 | + | 197 | ++++ | 243 | ++++ |
| 152 | ++++ | 198 | ++++ | 244 | +++ |
| 153 | ++++ | 199 | ++++ | 245 | ++++ |
| 154 | ++++ | 200 | ++++ | 246 | ++++ |
| 155 | ++++ | 201 | + | 247 | ++++ |
| 156 | ++++ | 202 | ++++ | 248 | ++++ |
| 157 | +++ | 203 | ++++ | 249 | +++ |
| 158 | +++ | 204 | ++++ | 250 | ++++ |
| 159 | ++++ | 205 | ++++ | 251 | + |
| 160 | ++++ | 206 | +++ | 252 | ++++ |
| 161 | ++++ | 207 | ++++ | 253 | ++++ |
| 162 | ++++ | 208 | ++++ | 254 | ++++ |
| 163 | ++++ | 209 | ++++ | 255 | ++++ |
| 164 | + | 210 | ++++ | 256 | ++++ |
| 165 | ++++ | 211 | ++++ | 257 | ++++ |
| 166 | ++++ | 212 | + | 258 | ++++ |
| 167 | ++++ | 213 | + | 259 | + |
| 168 | +++ | 214 | + | 260 | ++++ |
| 169 | ++++ | 215 | + | 261 | ++++ |
| 170 | ++++ | 216 | + | 262 | ++++ |
| 171 | + | 217 | ++++ | 263 | ++++ |
| 172 | ++++ | 218 | ++++ | 264 | ++++ |
| 173 | ++++ | 219 | +++ | 265 | ++++ |
| 174 | ++++ | 220 | + | 266 | ++++ |
| 175 | ++++ | 221 | +++ | 267 | +++ |
| 176 | ++++ | 222 | ++ | 268 | ++++ |
| 177 | +++ | 223 | ++++ | 269 | ++++ |
| 178 | ++++ | 224 | +++ | 270 | +++ |
| 271 | ++++ | 317 | ++++ | 363 | ++++ |
| 272 | ++++ | 318 | ++++ | 364 | ++++ |
| 273 | ++++ | 319 | ++++ | 365 | ++++ |
| 274 | ++++ | 320 | ++++ | 366 | ++++ |
| 275 | ++++ | 321 | ++++ | 367 | ++++ |
| 276 | ++++ | 322 | +++ | 368 | ++++ |
| 277 | +++ | 323 | ++++ | 369 | ++++ |
| 278 | + | 324 | ++++ | 370 | ++++ |
| 279 | ++++ | 325 | + | 371 | ++++ |
| 280 | ++++ | 326 | ++++ | 372 | ++++ |
| 281 | ++++ | 327 | ++++ | 373 | ++++ |
| 282 | ++++ | 328 | ++++ | 374 | ++++ |
| 283 | ++++ | 329 | ++++ | 375 | ++++ |
| 284 | +++ | 330 | ++++ | 376 | ++++ |
| 285 | ++++ | 331 | ++++ | 377 | ++++ |
| 286 | + | 332 | ++++ | 378 | ++++ |
| 287 | ++++ | 333 | ++++ | 379 | ++++ |
| 288 | ++++ | 334 | ++++ | 380 | ++++ |
| 289 | + | 335 | ++++ | 381 | ++++ |
| 290 | ++++ | 336 | ++++ | 382 | +++ |
| 291 | ++++ | 337 | ++++ | 383 | ++++ |
| 292 | ++++ | 338 | +++ | 384 | ++++ |
| 293 | ++++ | 339 | ++++ | 385 | ++++ |
| 294 | ++++ | 340 | +++ | 386 | ++++ |
| 295 | ++++ | 341 | ++++ | 387 | ++++ |
| 296 | ++++ | 342 | ++++ | 388 | ++++ |
| 297 | ++++ | 343 | ++++ | 389 | ++++ |
| 298 | ++++ | 344 | +++ | 390 | ++++ |
| 299 | +++ | 345 | ++++ | 391 | ++++ |
| 300 | ++++ | 346 | ++++ | 392 | ++++ |
| 301 | ++++ | 347 | ++++ | 393 | ++++ |
| 302 | +++ | 348 | ++++ | 394 | ++++ |
| 303 | ++++ | 349 | ++++ | 395 | ++++ |
| 304 | ++++ | 350 | ++++ | 396 | ++++ |
| 305 | ++++ | 351 | ++++ | 397 | ++++ |
| 306 | ++++ | 352 | +++ | 398 | ++++ |
| 307 | ++++ | 353 | ++++ | 399 | ++++ |
| 308 | +++ | 354 | + | 400 | ++++ |
| 309 | ++++ | 355 | + | 401 | ++++ |
| 310 | ++++ | 356 | ++++ | 402 | +++ |
| 311 | ++++ | 357 | ++++ | 403 | + |
| 312 | ++++ | 358 | ++++ | 404 | ++++ |
| 313 | + | 359 | ++++ | 405 | ++++ |
| 314 | + | 360 | ++++ | 406 | ++++ |
| 315 | ++++ | 361 | ++++ | 407 | ++++ |
| 316 | ++++ | 362 | ++++ | 408 | ++++ |
| 409 | ++++ | 455 | ++++ | 501 | ++++ |
| 410 | ++++ | 456 | ++ | 502 | ++++ |
| 411 | ++++ | 457 | ++++ | 503 | ++++ |
| 412 | ++++ | 458 | ++++ | 504 | ++++ |
| 413 | ++++ | 459 | +++ | 505 | ++++ |
| 414 | ++++ | 460 | ++++ | 506 | ++++ |
| 415 | ++++ | 461 | + | 507 | ++++ |
| 416 | ++++ | 462 | ++++ | 508 | ++++ |
| 417 | ++++ | 463 | ++++ | 509 | ++++ |
| 418 | ++++ | 464 | ++++ | 510 | ++++ |
| 419 | ++++ | 465 | ++++ | 511 | ++++ |
| 420 | ++++ | 466 | ++++ | 512 | ++++ |
| 421 | ++++ | 467 | ++++ | 513 | ++++ |
| 422 | ++++ | 468 | ++++ | 514 | ++++ |
| 423 | ++++ | 469 | ++++ | 515 | ++++ |
| 424 | ++++ | 470 | +++ | 516 | ++++ |
| 425 | ++++ | 471 | +++ | 517 | ++++ |
| 426 | ++++ | 472 | + | 518 | ++++ |
| 427 | ++++ | 473 | + | 519 | ++++ |
| 428 | ++++ | 474 | +++ | 520 | ++++ |
| 429 | ++++ | 475 | + | 521 | ++++ |
| 430 | ++++ | 476 | ++++ | 522 | ++++ |
| 431 | +++ | 477 | ++++ | 523 | ++++ |
| 432 | ++++ | 478 | ++ | 524 | ++++ |
| 433 | ++++ | 479 | ++++ | 525 | ++++ |
| 434 | ++++ | 480 | ++++ | 526 | ++++ |
| 435 | ++++ | 481 | ++++ | 527 | ++++ |
| 436 | ++++ | 482 | ++++ | 528 | ++++ |
| 437 | ++++ | 483 | ++++ | 529 | ++++ |
| 438 | ++++ | 484 | ++++ | 530 | ++++ |
| 439 | ++++ | 485 | ++++ | 531 | ++++ |
| 440 | ++++ | 486 | ++++ | 532 | ++++ |
| 441 | ++++ | 487 | ++++ | 533 | ++++ |
| 442 | ++++ | 488 | ++++ | 534 | ++++ |
| 443 | ++++ | 489 | ++++ | 535 | ++++ |
| 444 | ++++ | 490 | ++++ | 536 | ++++ |
| 445 | ++++ | 491 | ++++ | 537 | ++++ |
| 446 | ++++ | 492 | ++++ | 538 | ++++ |
| 447 | ++++ | 493 | ++++ | 539 | ++++ |
| 448 | ++++ | 494 | ++++ | 540 | ++++ |
| 449 | +++ | 495 | ++++ | 541 | ++++ |
| 450 | + | 496 | ++++ | 542 | ++++ |
| 451 | ++++ | 497 | ++++ | 543 | ++++ |
| 452 | ++++ | 498 | ++++ | 544 | ++++ |
| 453 | ++ | 499 | ++++ | 545 | ++++ |
| 454 | +++ | 500 | +++ | 546 | ++++ |
| 547 | ++++ | 592 | ++++ | 637 | ++++ |
| 548 | ++++ | 593 | ++++ | 638 | ++++ |
| 549 | + | 594 | ++++ | 639 | ++++ |
| 550 | ++++ | 595 | +++ | 640 | ++++ |
| 551 | + | 596 | ++++ | 641 | ++++ |
| 552 | ++++ | 597 | ++++ | 642 | ++++ |
| 553 | ++++ | 598 | ++++ | 643 | +++ |
| 554 | ++++ | 599 | ++++ | 644 | ++++ |
| 555 | ++++ | 600 | ++++ | 645 | ++++ |
| 556 | ++++ | 601 | ++++ | 646 | ++++ |
| 557 | ++++ | 602 | ++++ | 647 | ++++ |
| 558 | ++++ | 603 | ++++ | 648 | ++++ |
| 559 | ++++ | 604 | +++ | 649 | ++++ |
| 560 | ++++ | 605 | + | 650 | ++++ |
| 561 | ++++ | 606 | ++++ | 651 | ++++ |
| 562 | ++++ | 607 | ++++ | 652 | ++++ |
| 563 | ++++ | 608 | ++++ | 653 | ++++ |
| 564 | ++++ | 609 | ++++ | 654 | ++++ |
| 565 | ++++ | 610 | ++++ | 655 | ++++ |
| 566 | +++ | 611 | ++++ | 656 | ++++ |
| 567 | ++++ | 612 | ++++ | 657 | ++++ |
| 568 | ++++ | 613 | ++++ | 658 | ++++ |
| 569 | ++++ | 614 | ++++ | 659 | ++++ |
| 570 | ++++ | 615 | ++++ | 660 | ++++ |
| 571 | ++++ | 616 | ++++ | 661 | ++++ |
| 572 | ++++ | 617 | ++++ | 662 | ++++ |
| 573 | ++++ | 618 | ++++ | 663 | ++++ |
| 574 | ++++ | 619 | ++++ | 664 | ++++ |
| 575 | ++++ | 620 | ++++ | 665 | ++++ |
| 576 | + | 621 | ++++ | 666 | +++ |
| 577 | ++++ | 622 | ++++ | ||
| 578 | ++++ | 623 | ++++ | ||
| 579 | ++++ | 624 | ++++ | ||
| 580 | ++++ | 625 | ++++ | ||
| 581 | ++++ | 626 | ++++ | ||
| 582 | ++++ | 627 | ++++ | ||
| 583 | ++++ | 628 | ++++ | ||
| 584 | +++ | 629 | ++++ | ||
| 585 | ++++ | 630 | ++++ | ||
| 586 | ++++ | 631 | ++++ | ||
| 587 | ++++ | 632 | ++++ | ||
| 588 | ++++ | 633 | ++++ | ||
| 589 | ++++ | 634 | ++++ | ||
| 590 | ++++ | 635 | ++++ | ||
| 591 | ++++ | 636 | ++++ |
人類周邊泛T
細胞的IFNγ
及IL-2
分析
人類周邊血泛T細胞購自STEMCELL
TMTechnologies Inc.。將人
類周邊血泛T細胞解凍並懸浮在DMEM培養基(10%FBS和1%青黴素/鏈黴素)中。 將8 X 10
4T細胞接種在96孔盤中，並與不同濃度的化合物和100nM前列腺素E2培養1小時。用Dynabeads人類T-活化劑CD3/CD28(Life Technologies)以1:3的細胞：珠比例刺激T細胞。按照製造商的建議，使用MSD V-PLEX人類細胞激素試劑組在刺激後24小時測量細胞激素分泌。用MESO Quickplex SQ120(Mesoscale Discovery)分析數據。
在表3中，值+表示為＞1000nM，++為200-1,000nM，+++為
＜200nM，和–為未測定。
表3. 本發明化合物在人類周邊血泛T細胞中的IFNγ和IL-2分
泌
| 實施例 | IFNγ (EC 50) | IL-2 (EC 50) | 實施例 | IFNγ (EC 50) | IL-2 (EC 50) |
| 104 | ++ | + | 333 | ++ | ++ |
| 105 | ++ | + | 334 | ++ | ++ |
| 107 | ++ | - | 359 | ++ | ++ |
| 110 | +++ | - | 361 | ++ | + |
| 111 | ++ | - | 484 | +++ | ++ |
| 118 | +++ | - | 488 | ++ | - |
| 123 | ++ | + | 503 | ++ | - |
| 125 | +++ | - | 509 | +++ | ++ |
| 134 | +++ | + | 520 | ++ | - |
| 152 | ++ | ++ | 521 | +++ | +++ |
| 156 | ++ | ++ | 523 | +++ | - |
| 161 | ++ | - | 524 | +++ | +++ |
| 162 | ++ | - | 525 | +++ | ++ |
| 163 | - | - | 529 | +++ | +++ |
| 167 | ++ | + | 530 | ++ | ++ |
| 169 | ++ | + | 531 | +++ | ++ |
| 170 | ++ | + | 532 | ++ | - |
| 172 | ++ | - | 534 | +++ | - |
| 173 | ++ | - | 541 | ++ | - |
| 174 | ++ | - | 543 | +++ | ++ |
| 175 | +++ | - | 548 | - | - |
| 178 | - | - | 550 | ++ | ++ |
| 184 | +++ | - | 552 | ++ | ++ |
| 193 | ++ | + | 556 | +++ | ++ |
| 194 | ++ | - | 557 | +++ | ++ |
| 196 | ++ | - | 558 | +++ | ++ |
| 199 | ++ | - | 561 | ++ | ++ |
| 258 | +++ | ++ | 562 | ++ | - |
| 291 | +++ | ++ | 563 | ++ | ++ |
| 293 | +++ | - | 564 | ++ | ++ |
| 296 | +++ | ++ | 565 | ++ | ++ |
| 297 | +++ | +++ | 569 | ++ | + |
| 316 | ++ | + | 570 | +++ | ++ |
| 320 | ++ | - | 574 | ++ | ++ |
| 324 | +++ | ++ | 577 | +++ | ++ |
| 326 | ++ | ++ | 579 | +++ | + |
| 327 | +++ | ++ | 588 | +++ | +++ |
| 329 | ++ | ++ | |||
| 330 | ++ | ++ | |||
| 332 | ++ | ++ |
無
Claims (34)
- 一種化合物或其藥學上可接受的鹽、水合物或溶劑化物，其特徵係該化合物如式(I)所示：式(I)， 其中： X是O或S； L是鍵、-O-、-S-、或-NR 6-； R 1為烷基、環烷基、芳基、雜芳基或雜環基，其中R 1任選地被一個或多個獨立選自R 7的取代基取代； R 6為-H或C 1-6烷基； R 7為C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、氧代、氰基、羥基、-C(O)R 9、 -C(O)OR 9、 -C(O)NR 10R 11、-OR 9、-OC(O)R 9、-OC(O)NR 10R 11、-SR 9、 -S(O)R 9、-S(O) 2R 9、 -S(O)(=NH)R 10、-S(O) 2NR 10R 11、-NR 10R 11、-N(R 6)NR 10R 11、-N(R 6)OR 9、-N(R 6)C(O)R9、-N(R 6)C(O)OR 9、-N(R 6)C(O)NR 10R 11、-N(R 6)S(O) 2R 9、 -N(R 6)S(O) 2NR 10R 11, 或-P(O)R 12R 13； R 9為-H、C 1-6烷基、C 1-6鹵代烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基或雜環基； 每個R 10及R 11獨立地為-H、C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基或雜環基，或R 10及R 11與其等所連接的氮原子一起形成4-到12-元雜環基，雜環基任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥烷基、-CN, -NO 2, -NR 10R 11, -NR 10C(=O)R 9、-NR 10C(=O)NR 10R 11、-NR 10C(=O)OR 9、-OR 9、-C(=O)R 9、 -C(=O)OR 9、 -C(=O)NR 10R 11、 -OC(=O)R 9、-OC(=O)OR 9及 -OC(=O)NR 10R 11； 每個R 12及R 13獨立地為C 1-6烷基，C 1-6烷氧基、C 3-8環烷基、芳基、雜芳基、雜環基，或R 12及R 13與其等所連接的磷原子一起形成4-到8-元雜環基，雜環基任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥烷基、-CN、-NO 2、-NR 10R 11、-NR 10C(=O)R 9、 -NR 10C(=O)NR 10R 11、-NR 10C(=O)OR 9、-OR 9、-C(=O)R 9、-C(=O)OR 9、-C(=O)NR 10R 11、 -OC(=O)R 9、-OC(=O)OR 9及 -OC(=O)NR 10R 11； Het選自由下列基團組成之群組：
； R a、R b及R c各自獨立地為-H、-D、鹵代、CF 3、CF 2H、CH 2F、CN、OR 9或NR 10R 11； R 2為-H、-D、-CD 3、C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、羥基、-CD 2OH、-CN、-NO 2、鹵代烷基、三甲基矽烷乙氧基甲基、-C(O)R 9、-C(O)OR 9、-C(O)NR 10R 11、 -OR 9、 -OC(O)R 9、-OC(O)N R 10R 11、-SR 9、-S(O)R 9、-S(O) 2R 9、-S(O)(=NH)R 10、-S(O) 2NR 10R 11、-NR 10R 11、-N(R 6)NR 10R 11、-N(R 6)OR 9、-N(R 6)C(O)R 9、-N(R 6)C(O)R 9、-N(R 6)C(O)OR 9、-N(R 6)C(O)NR 10R 11、-N(R 6)S(O) 2R 9、-N(R 6)S(O) 2NR 10R 11或-P(O)R 12R 13，其中C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基、或雜環基可任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥烷基、-CN、-NO 2、-NR 10R 11、-NR 10C(=O)R 9、-NR 10C(=O)NR 10R 11、-NR 10C(=O)OR 9、-OR 9、-C(=O)R 9、-C(=O)OR 9、-C(=O)NR 10R 11、 -OC(=O)R 9、-OC(=O)OR 9及-OC(O=)NR 10R 11； R 3為-H、-D、-CD 3、C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、氰基、羥基、 -CH 2OH、-CD 2OH、-OH、-CN、 -NO 2、鹵代烷基、-C(O)R 9、-C(O)OR 9、-C(O)NR 10R 11、-OR 9、-OC(O)R 9, -OC(O)NR 10R 11、-SR 9、-S(O)R 9、-S(O) 2R 9、-S(O)(=NH)R 10、-S(O )2NR 10R 11、-NR 10R 11、-N(R 6)NR 10R 11, -N(R 6)OR 9、-N(R 6)C(O)R 9、-N(R 6)C(O)OR 9、-N(R 6)C(O)NR 10R 11、-N(R 6)S(O) 2R 9、 -N(R 6)S(O) 2NR 10R 11，或-P(O)R 12R 13； M是鍵、-O-、-S-或-NR 6-； R 6為-H或C 1-6烷基； R 4為-H、-D、C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、氰基、羥基、-C(O)R 9、-C(O)OR 9、-C(O)NR 10R 11、-S(O) 2R 9、-S(O)(=NH)R 10、-S(O) 2NR 10R 11或-P(O)R 12R 13，其中C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基，或雜環基任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥烷基、-CN、-CD 3、-NO 2、-NR 10R 11、-NR 10C(=O)R 9、-NR 10C(=O)NR 10R 11、-NR 10C(=O)OR 9、-NR 10S(O) 2R 9、-OR 9、-C(=O)R 9、-C(=O)OR 9、-C(=O)NR 10R 11、-OC(=O)R 9、-OC(=O)OR 9及-OC(=O)NR 10R 11；及 R 5為-H、-D、-CD 3、C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、鹵代、羥基、-CH 2OH、-CD 2OH、-CN或鹵代烷基。
- 如請求項1所述之化合物或其藥學上可接受的鹽，其中，L為鍵，R 1為環烷基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、鹵代、氰基、羥基、-C(O)R 9、-C(O)OR 9、-C(O)R 10R 11、-OR 9、-OC(O)R 9、-OC(O)NR 10R 11、-NR 10R 11、-N(R 6)NR 10R 11、-N(R 6)OR 9、-N(R 6)C(O)R 9、-N(R 6)C(O)OR 9及-N(R 6)C(O)NR 10R 11。
- 如請求項1所述之化合物或其藥學上可接受的鹽，其中，R 2及R 3中之每一個獨立地為-H、鹵代、烷基硫基、鹵代烷基或烷基。
- 如請求項1所述之化合物或其藥學上可接受的鹽，其中，M是鍵、-O-或-NR 6-；及R 4為-H、-D、C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基、雜環基、鹵代、氰基、羥基、-C(O)R 9、-C(O)NR 10R 11、-S(O) 2R 9、-S(O)(=NH)R 10或-S(O) 2NR 10R 11，其中，C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、芳基、雜芳基，或雜環基任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、羥基、烷基、烯基、炔基、鹵代烷基、羥基烷基、-CN、-CD 3、-NR 10R 11、-NR 10S(O) 2R 9及-NR 10C(=O)R 9。
- 如請求項1所述之化合物或其藥學上可接受的鹽，其中，式(II)所示之化合物：式(II)。
- 如請求項5所述之化合物或其藥學上可接受的鹽，其中，L為鍵，R 1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C 1-3烷基硫基、C 1-3烷基、C 1-3羥烷基及C 1-3鹵代烷基；R 2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R 3為–H、烷基或鹵代；M是鍵、-O-、-S-或-NR 6-；R 4為–H、鹵代、烷基、羥烷基、鹵代烷基、鹵代烯基、環烷基、氰基烷基、二甲胺基、二甲胺基乙基、二甲胺基羰基、甲胺基氧乙基、胺基羰基烷基、乙醯胺基乙基、丙醯胺基乙基、甲醯胺基乙基、胺基烷基、甲胺基羰基甲基、烷氧基烷基、氮雜環丁烷基或氮雜環丁烷基甲基；R 5為–H、烷基或鹵代。
- 如請求項5所述之化合物或其藥學上可接受的鹽，其中，其選自由表1中實施例1至145之化合物組成之群組。
- 如請求項5所述之化合物或其藥學上可接受的鹽，其中，其選自下列組成之群組： (1S,2S)-N-(6-(5-氯-6-氟-7-(甲硫基)-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-甲氧基-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-((2-胺基乙基)(甲基)胺基)-5-氯-6-氟-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-((2-(二甲胺基)乙基)(甲基)胺基)-6-氟-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-((2-(甲胺基)-2-氧乙基)硫代)-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲基(2-(甲胺基)乙基)胺基)-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-((氮雜環丁烷-3-基甲基)(甲基)胺基)-5-氯-6-氟-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-7-甲氧基-5-甲基-1H-吲唑-4-基)苯並[d]噻唑-2-基)環丙烷甲醯胺； (1S,2S)-N-(6-(7-乙氧基-6-氟-5-甲基-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5,7-雙(甲硫基)-1H-吲唑-4-基)苯並[d]噻唑-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-乙氧基-6-氟-5-(甲硫基)-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(N-甲基乙醯胺)-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺； 5-氯-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺)苯並[d]噻唑-6-基)-N,N-二甲基-1H-吲唑-7-甲醯胺； (1S,2S)-N-(6-(7-(氮雜環丁烷-3-基(甲基)胺基)-5-氯-6-氟-1H-吲唑-4-基)苯並[d]噻唑-2-基)-2-氟環丙烷-1-甲醯胺；及 6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)苯並[d]噻唑-6-基)-N,N, 5-三甲基-1H-吲唑-7-甲醯胺。
- 如請求項1所述之化合物或其藥學上可接受的鹽，其中，式(III)所示化合物：式(III)。
- 如請求項9所述之化合物或其藥學上可接受的鹽，其中，L為鍵，R 1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C 1-3烷基、C 1-3羥烷基及C 1-3鹵代烷基；R 2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R 3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR 6-；R 4為–H、鹵代、烷基、羥烷基、二甲胺基、二甲胺基乙基、二甲胺基羰基、甲胺基氧乙基、胺基羰基烷基、乙醯胺基乙基或烷氧基烷基；R 5為–H、烷基或鹵代。
- 如請求項9所述之化合物或其藥學上可接受的鹽，其中，其選自由表1中實施例146至218之化合物組成之群組。
- 如請求項9所述之化合物或其藥學上可接受的鹽，其中，其選自下列組成之群組： (1S,2S)-N-(5-(5-氯-7-乙氧基-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5-(甲硫基)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(乙胺基)-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-(二甲胺基)-5-乙基-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-6-氟-7-(甲硫基)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-7-((2-羥乙基)硫代)-5-甲基-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-6-氟-7-((2-(甲胺基)-2-氧乙基)硫代)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-(二甲胺基)-6-氟-5-甲基-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5,7-雙(甲硫基)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5-甲基-7-(甲硫基)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(甲硫基)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-乙氧基-6-氟-5-甲基-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-乙氧基-5-乙基-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-乙氧基-6-氟-5-(甲硫基)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； 5-氯-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺)噻唑[5,4-b]吡啶-5-基)-N,N-二甲基-1H-吲唑-7-甲醯胺； (1S,2S)-N-(5-(7-(二甲胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N(5-(5-氯-7-(乙基(甲基)胺基)-6-氟-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5,7-二甲基-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)環丙烷-1-甲醯胺；及 (1S,2S)-N-(5-(7-(乙基(甲基)胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)噻唑[5,4-b]吡啶-2-基)-2-氟環丙烷-1-甲醯胺。
- 如請求項1所述之化合物或其藥學上可接受的鹽，其中，式(IV)所示化合物：式(IV)。
- 如請求項13所述之化合物或其藥學上可接受的鹽，其中，L為鍵，R 1為環丙基，其任選地其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C 1-3烷基、C 1-3羥烷基及C 1-3鹵代烷基；R 2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R 3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR 6-；R 4為–H、鹵代、烷基、羥烷基、鹵代烷基、鹵代烯基、環烷基、氰基烷基、二甲胺基、二甲胺基乙基、二甲胺基羰基、甲胺基氧乙基、胺基羰基烷基、乙醯胺基乙基、丙醯胺基乙基、甲醯胺基乙基、環烷基烷基、環烷基(羥基)烷基、羥基環烷基、甲氧基環烷基、環烷基(甲氧基)甲基、烷氧基烷基、烯基、甲基磺醯胺基乙基、咪唑基乙基、二噁烷基、環丁基羰基胺基乙基、二氟乙醯胺基乙基、三氟乙醯胺基乙基、甲基硫代甲基、甲基硫代乙基、氮雜環丁烷基、氮雜環丁烷基甲基、環丙基羰基胺基(氰基)甲基、氰基(二氟乙醯胺基)甲基、丙基-1,1,3,3,3-d6)胺基、四氫呋喃基、甲基咪唑基乙基、呋喃基、吡咯基、甲基吡咯基、異噁唑基、四唑基烷基、甲基吡唑基或甲基吡唑基甲基；R 5為–H、烷基或鹵代。
- 如請求項13所述之化合物或其藥學上可接受的鹽，其中，其選自由表1中實施例219及220之化合物組成之群組。
- 如請求項1所述之化合物或其藥學上可接受的鹽，其中，式(V)所示化合物：式(V)。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，L為鍵，R 1為環烷基，其任選地其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：C 1-6烷基、C 2-6烯基、C 2-6炔基、環烷基、鹵代、氰基、羥基、-C(O)R 9、-C(O)OR 9、-C(O)NR 10R 11、-OR 9、-OC(O)R 9、-OC(O)NR 10R 11、-NR 10R 11、-N(R 6)NR 10R 11、-N(R 6)OR 9、-N(R 6)C(O)R 9、-N(R 6)C(O)OR 9及-N(R 6)C(O)NR 10R 11。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，R 1為環烷基，其任選地其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C 1-3烷基、C 1-3羥烷基及C 1-3鹵代烷基。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，其選自表1中的實施例221至445之化合物組成之群組。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，R 1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C 1-C 3烷基、C 1-C 3羥烷基及C 1-C 3鹵代烷基；R 2為–H、烷基、烷基硫基、鹵代烷基或鹵代；R 3為–H、烷基或鹵代；M為鍵、-O-或-NR 6-；R 4為–H、鹵代、烷基、單烷基胺基或二烷基胺基；R 5為–H、烷基或鹵代。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，其選自： (1S,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-(三氟甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(異丙基胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；及 (1S,2S)-N-(6-(5-氯-6-氟-7-異丙基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，R 1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C 1-3烷基、C 1-3羥烷基及C 1-3鹵代烷基；R 2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R 3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR 6-；R 4為–H、鹵代、烷基、羥烷基、鹵代烷基、鹵代烯基、環烷基、單烷基胺基或二烷基胺基；及R 5為–H、烷基或鹵代。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，其選自： (1S,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-溴-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5-甲基-7-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-甲氧基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-乙氧基-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(乙胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-乙氧基-6-氟-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-5-乙基-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-乙基-6-氟-7-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5,7-雙(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(6,7-二氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(乙基(甲基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-乙氧基-6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-乙氧基-5-乙基-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； 5-氯-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺)咪唑[1,2-a]吡啶-6-基)-N,N-二甲基-1H-吲唑-7-甲醯胺； (1S,2S)-N-(6-(7-(乙基(甲基)胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷甲醯胺； 6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)咪唑[1,2-a]吡啶-6-基)-N,N,5-三甲基-1H-吲唑-7-甲醯胺； (1S,2S)-N-(6-(7-(乙基(甲基)胺基)-6-氟-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1R,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1R,2R)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(2-氧吡咯烷-1-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； 5-氯-N-乙基-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)咪唑[1,2-a]吡啶-6-基)-N-甲基-1H-吲唑-7-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5-甲基-7-(三氟甲氧基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲基(吡啶-3-基甲基)胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲基(吡啶-4-基甲基)胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(三氟甲氧基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(3-甲基-2-氧代咪唑啶-1-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(異丙基胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(環丙基(甲基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-((氰甲基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-((1-氰乙基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-羥乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-氟乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲氧基甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(乙氧基甲基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(1-(2H-四唑-2-基)乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-異丙氧基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-異丙基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-((S)-1-(2H-四唑-2-基)乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(2-羥基環戊基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-((S)-1-(1H-四唑-1-基)乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(1-乙醯胺乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1,2,2,2-四氟乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-((R)-1-甲氧基丙烷-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-((S)-1-甲氧基丙烷-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-((1,1-二氟丙烷-2-基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-甲醯胺乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-(2,2,2-三氟乙醯胺基)乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； N-(1-(5-氯-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺)咪唑[1,2-a]吡啶-6-基)-1H-吲唑-7-基)乙基)環丁烷甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-(甲胺基)-1-氧丙烷-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-((甲硫基)甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-(甲硫基)乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(氰基(甲醯胺)甲基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(1-(2,2-二氟乙醯胺基)乙基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；及 (1S,2S)-N-(6-(5-氯-7-(1-(乙胺基)-1-氧丙烷-2-基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，R 1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C 1-3烷基、C 1-3羥烷基及C 1-3鹵代烷基；R 2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R 3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR 6-；R 4為–H、鹵代、烷基、烷基羰基、二烷基胺基羰基、氧吡咯烷基、羥基烷基、鹵代烷基、鹵代烯基、環烷基、吡啶基、單烷基胺基或二烷基胺基；及R 5為–H、烷基或鹵代。
- 如請求項16所述之化合物或其藥學上可接受的鹽，其中，其選自： (1S,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-溴-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-溴-6-氟-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5-甲基-7-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-7-甲氧基-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-甲氧基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-乙氧基-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(乙胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(二乙胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-乙氧基-6-氟-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-((2-羥乙基)硫代)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-5-乙基-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-乙基-6-氟-7-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5,7-雙(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-乙基-6,7-二氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(6,7-二氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(乙基(甲基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二甲胺基)-6-氟-5-(三氟甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-乙氧基-6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(N-甲基乙醯胺)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-乙氧基-5-乙基-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； 5-氯-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺)咪唑[1,2-a]吡啶-6-基)-N,N-二甲基-1H-吲唑-7-甲醯胺； (1S,2S)-N-(6-(7-(乙基(甲基)胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-乙基-7-(乙基(甲基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷甲醯胺； 6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)咪唑[1,2-a]吡啶-6-基)-N,N,5-三甲基-1H-吲唑-7-甲醯胺； (1S,2S)-N-(6-(7-(乙基(甲基)胺基)-6-氟-5-甲基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(二氟甲基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1R,2S)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2R)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1R,2R)-N-(6-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(2-氧吡咯烷-1-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-乙基-6-氟-7-(三氟甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； 5-氯-N-乙基-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)咪唑[1,2-a]吡啶-6-基)-N-甲基-1H-吲唑-7-甲醯胺； (1S,2S)-2-氟-N-(6-(6-氟-5-甲基-7-(三氟甲氧基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲基(嘧啶-2-基)胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲基(吡啶-3-基甲基)胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲基(吡啶-4-基甲基)胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(三氟甲氧基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(3-甲基-2-氧代咪唑啶-1-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(異丙基胺基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(環丙基(甲基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(羥甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(氟甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1H-吡咯-1-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-((氰甲基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(環丙基胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(二級-丁胺基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-((1-氰乙基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-羥乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-甲氧基乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-氟乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-甲基-1H-吡咯-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-甲基-1H-吡唑-5-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-((2H-四唑-2-基)甲基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-((2H-1,2,3-三唑-2-基)甲基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(2-甲基-1H-吡咯-1-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(甲氧基甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(乙氧基甲基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(1-(2H-四唑-2-基)乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(1-(1H-四唑-1-基)乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-環丙氧基-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-異丙氧基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-異丙基-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-環戊基-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-((S)-1-(2H-四唑-2-基)乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(2,2,2-三氟-1-羥乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(2-羥基環戊基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-((S)-1-(1H-四唑-1-基)乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(2,2,2-三氟-1-甲氧基乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(7-(1-乙醯胺乙基)-5-氯-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1,2,2,2-四氟乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-((環丙基甲基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-((R)-1-甲氧基丙烷-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-((S)-1-甲氧基丙烷-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-丙醯胺基乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-((1,1-二氟丙烷-2-基)胺基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-甲醯胺乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-(2,2,2-三氟乙醯胺基)乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； N-(1-(5-氯-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺)咪唑[1,2-a]吡啶-6-基)-1H-吲唑-7-基)乙基)環丁烷甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-(甲胺基)-1-氧丙烷-2-基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-((甲硫基)甲基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-6-氟-7-(1-(甲硫基)乙基)-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(氰基(甲醯胺)甲基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(6-(5-氯-7-(1-(2,2-二氟乙醯胺基)乙基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；及 (1S,2S)-N-(6-(5-氯-7-(1-(乙胺基)-1-氧丙烷-2-基)-6-氟-1H-吲唑-4-基)咪唑[1,2-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺。
- 如請求項1所述之化合物或其藥學上可接受的鹽，其中，其是(VI)所示化合物：式(VI)。
- 如請求項26所述之化合物或其藥學上可接受的鹽，其中，L為鍵，R 1為環丙基，其任選地被一個或多個基團所取代，該基團選自由下列組成之群組：鹵代、C 1-3烷基、C 1-3羥烷基及C 1-3鹵代烷基；R 2為–H、烷基、鹵代、鹵代烷基或烷基硫基；R 3為–H、烷基或鹵代；M為鍵、-O-、-S-或-NR 6-；R 4為–H、鹵代、烷基、羥烷基、鹵代烷基、鹵代烷基醯胺基烷基、鹵代烷基羰基胺基烷基、烷基胺基烷基、羥基鹵代烷基、鹵代烯基、環烷基、氰基、氰基烷基、二甲胺基、二甲胺基乙基、甲胺基羰基、二甲胺基羰基、甲胺基氧乙基、胺基羰基烷基、乙醯胺基乙基、二烷基胺基環烷基，胺基環烷基、甲胺基環烷基、環烷基烷基、環烷基(羥基)烷基、環烷基醯胺烷基、環烷基胺基羰基、羥基環烷基、甲氧基環烷基、環烷基(甲氧基)甲基、烷氧基羰基、烷基羰基、烷基醯胺烷基、烷氧基烷基、烯基、甲基磺醯胺基乙基、咪唑基乙基、二噁烷基、氮雜環丁烷基、氮雜環丁烷基甲基、四氫呋喃基、呋喃基、嘧啶基、吡啶基、吡咯基、鹵代吡咯烷基、吡咯烷基、甲基吡咯基、異噁唑基、四唑烷基、三嗪基、甲基吡唑基或甲基吡唑基甲基；R 5為–H、烷基或鹵代。
- 如請求項26所述之化合物或其藥學上可接受的鹽，其中，其選自表1中的實施例446至666之化合物組成之群組。
- 如請求項26所述之化合物或其藥學上可接受的鹽，其中，其選自： (1S,2S)-N-(5-(5-溴-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5-甲氧基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5,7-二氯-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5,7-二甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-溴-5-氯-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-溴-6-氟-5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5-甲基-7-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-(二甲胺基)-6-氟-5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-7-甲氧基-5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-甲氧基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-乙氧基-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(甲胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(乙胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(二乙胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-((4-(二甲胺基)環己基)(甲基)胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-((4-羥基環己基)(甲基)胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(甲基((1R,4R)-4-(甲胺基)環己基)胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(甲基((1S,4S)-4-(甲胺基)環己基)胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-乙氧基-6-氟-5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-6-氟-7-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺二鹽酸鹽； (1S,2S)-N-(5-(7-((4-胺基環己基)(甲基)胺基)-5-氯-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-(二甲胺基)-5-乙基-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-((2-羥乙基)硫代)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-6-氟-7-((2-(甲胺基)-2-氧乙基)硫代)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺雙(2,2,2-三氟乙酸)； (1S,2S)-2-氟-N-(5-(6-氟-7-((2-羥乙基)硫代)-5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-7-(乙基胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-7-(乙基(甲基)胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5,7-雙(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-乙氧基-5-乙基-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-6,7-二氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-7-(2-羥基乙氧基)-5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(6,7-二氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-乙氧基-6-氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； 甲基6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)吡唑[1,5-a]吡啶-5-基)-5-甲基-1H-吲唑-7-羧酸鹽； (1S,2S)-2-氟-N-(5-(6-氟-5-甲基-7-(N-甲基乙醯胺)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(N-甲基乙醯胺)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； 5-氯-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)吡唑[1,5-a]吡啶-5-基)-N,N-二甲基-1H-吲唑-7-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-7-((2-羥乙基)(甲基)胺基)-5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-(二甲胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-((3-羥基環丁基)(甲基)胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； N-(5-(6-氟-5-甲基-7-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷甲醯胺； (1S,2S)-N-(5-(7-(乙基(甲基)胺基)-6-氟-5-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(乙基(甲基)胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-(二甲胺基)-6-氟-5-(三氟甲基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1R,2S)-2-氟-N-(5-(6-氟-5-甲基-7-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； N-(5-(6-氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷甲醯胺； 6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)吡唑[1,5-a]吡啶-5-基)-N,N,5-三甲基-1H-吲唑-7-甲醯胺； (1R,2S)-2-氟-N-(5-(6-氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2R)-2-氟-N-(5-(6-氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1R,2R)-2-氟-N-(5-(6-氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1R,2R)-2-氟-N-(5-(6-氟-5-甲基-7-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-(乙基(甲基)胺基)-6-氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-甲基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(二氟甲基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-乙基-6-氟-7-(三氟甲基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-氰基-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-((氰甲基)硫代)-5-乙基-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-2-氟-N-(5-(6-氟-5-甲基-7-(三氟甲氧基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(甲基(嘧啶-2-基)胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-((氰甲基)硫代)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1R,2R)-N-(5-(6,7-二氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2R)-N-(5-(6,7-二氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1R,2S)-N-(5-(6,7-二氟-5-(甲硫基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-((1-氰乙基)硫代)-5-乙基-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(三氟甲氧基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； 5-氯-N-(氰甲基)-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺基)吡唑[1,5-a]吡啶-5-基)-N-甲基-1H-吲唑-7-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(N-(氰甲基)乙醯胺)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(甲基(1,3,5-三嗪-2-基)胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(甲基(1,2,4-三嗪-3-基)胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(異丙基胺基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(乙硫基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(3-甲基-2-氧代咪唑啶-1-基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(環丙基(甲基)胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(羥甲基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(氟甲基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-((氰甲基)胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(1H-吡咯-1-基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-((2-氰基丙烷-2-基)胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(丙-1-烯-2-基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-異丙基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-((1-氰乙基)胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(3-氟吡咯烷-1-基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(2-甲基-1H-吡咯-1-基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2R,3S)-N-(5-(5-氯-7-(二甲胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-甲基-3-(1-甲基-1H-吡唑-4-基)環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-異丙氧基-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-環戊基-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(2,2,2-三氟-1-羥乙基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-((R)-1-甲氧基丙烷-2-基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-((S)-1-甲氧基丙烷-2-基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-((1,1-二氟丙烷-2-基)胺基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(1-甲醯胺乙基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(1-丙醯胺基乙基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； N-(1-(5-氯-6-氟-4-(2-((1S,2S)-2-氟環丙烷-1-甲醯胺)吡唑[1,5-a]吡啶-5-基)-1H-吲唑-7-基)乙基)環丁烷甲醯胺； (1S,2S)-N-(5-(5-氯-6-氟-7-(1-(2,2,2-三氟乙醯胺基)乙基)-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(7-(1-乙醯胺乙基)-5-氯-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺； (1S,2S)-N-(5-(5-氯-7-(1,3-二甲基脲基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺；及 (1S,2S)-N-(5-(5-氯-7-(1-(2,2-二氟乙醯胺基)乙基)-6-氟-1H-吲唑-4-基)吡唑[1,5-a]吡啶-2-基)-2-氟環丙烷-1-甲醯胺。
- 一種藥物組成物，其特徵係其包含藥學上可接受之載體或稀釋劑及如請求項1所述之化合物或其藥學上可接受的鹽。
- 一種治療患有與HPK1調節相關疾病或病症的受試者之方法，其特徵係其包含：向有需要的受試者施用治療有效量之如請求項1所述之化合物或其藥學上可接受的鹽。
- 如請求項31所述之方法，其中，該疾病為癌症，其中如請求項1所述之化合物與抗PD-1劑、抗PD-L1劑或抗CTLA4劑一起施用。
- 如請求項32所述之方法，其中，該疾病為癌症、轉移、炎症或自體免疫疾病。
- 如請求項33所述之方法，其中，該癌症選自下列組成之群組：腫瘤癌、黑色素瘤、胚細胞瘤、肉瘤、淋巴瘤及白血病，包含但不限於膀胱癌、腦瘤、乳腺癌、子宮頸癌、大腸直腸癌、食道癌、子宮內膜癌、肝細胞癌、喉癌、肺癌、骨肉瘤、卵巢癌、胰腺癌、前列腺癌、腎癌和甲狀腺癌、急性淋巴球白血病、急性骨髓性白血病、室管膜瘤、尤文氏肉瘤、神經膠母細胞瘤、髓母細胞瘤、 神經胚細胞瘤、橫紋肌肉瘤、橫紋肌樣癌及腎胚細胞瘤(威爾姆氏腫瘤)。
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