TWI543969B - Multifunctional quinoline derivatives as anti-neurodegenerative agents - Google Patents

Multifunctional quinoline derivatives as anti-neurodegenerative agents Download PDF

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TWI543969B
TWI543969B TW102115224A TW102115224A TWI543969B TW I543969 B TWI543969 B TW I543969B TW 102115224 A TW102115224 A TW 102115224A TW 102115224 A TW102115224 A TW 102115224A TW I543969 B TWI543969 B TW I543969B
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quinolin
undec
hydrogen
chloro
compound
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TW201441195A (en
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陳基旺
黃振瑋
張佩德
立卡 塔
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安基生技新藥股份有限公司
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作為抗神經退化劑之多官能性喹啉衍生物 Polyfunctional quinoline derivative as anti-neurodegradant

本發明係關於一種用於治療神經退化性疾病之化合物或其醫藥可接受性鹽類、溶劑化物或水合物、前藥或代謝物。 The present invention relates to a compound for the treatment of a neurodegenerative disease or a pharmaceutically acceptable salt, solvate or hydrate, prodrug or metabolite thereof.

美國專利第7,439,243號及第7,452,888號揭示一系列的喹啉衍生物，其可用於治療CNS異常，包括阿茲海默症。美國專利第7,009,053號記載一系列的喹啉衍生物可用於治療阿茲海默症、亨丁頓氏症、帕金森氏症、肌萎縮性側索硬化症、中風、局部缺血、創傷性腦損傷、脊髓損傷或骨關節炎。 U.S. Patent Nos. 7,439,243 and 7,452,888 disclose a series of quinoline derivatives useful for the treatment of CNS abnormalities, including Alzheimer's disease. U.S. Patent No. 7,009,053 describes a series of quinoline derivatives useful in the treatment of Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, ischemia, traumatic brain Injury, spinal cord injury or osteoarthritis.

於一方面，本發明係關於一種式(I)化合物或其醫藥可接受性鹽類、溶劑化物或水合物、前藥或代謝物： 其中R1為氫、(C1-C8)烷基、(C1-C8)伸烷基(C3-C8)環烷基、(C1-C8)鹵烷基或(C1-C8)伸烷基(C6-C20)芳基；R2為氫或鹵素；R3為氫、鹵素、(C1-C8)烷基或(C1-C8)烷氧基；R4為氫、鹵素、(C1-C8)烷基、(C1-C8)烷氧基或(C1-C8)鹵烷基；R5為氫或(C1-C20)烷醇；R6為氫；且R7為氫、(C1-C20)烷醇、(C1-C8)伸烷基(C3-C8)雜環基(C1-C20)烷醇、(C1-C8)伸烷基(C3-C8)雜環基(C1-C20)烷基、(C1-C8)伸烷基(C1-C6)烷基胺基(C1-C6)炔基、(C1-C8)伸烷基胺基(C1-C20)烷醇或(C1-C8)伸烷基胺基(C1-C20)烷醇(C1-C8)伸烷基取代之(C3-C20)雜芳基。 In one aspect, the invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, solvate or hydrate, prodrug or metabolite thereof: Wherein R 1 is hydrogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkyl (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )haloalkyl or (C) 1 -C 8 )alkyl (C 6 -C 20 ) aryl; R 2 is hydrogen or halogen; R 3 is hydrogen, halogen, (C 1 -C 8 )alkyl or (C 1 -C 8 ) alkane Alkyl; R 4 is hydrogen, halogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy or (C 1 -C 8 )haloalkyl; R 5 is hydrogen or (C 1 -C 20 ) an alkanol; R 6 is hydrogen; and R 7 is hydrogen, (C 1 -C 20 ) alkanol, (C 1 -C 8 )alkyl (C 3 -C 8 )heterocyclyl (C 1 - C 20 ) alkanol, (C 1 -C 8 )alkyl (C 3 -C 8 )heterocyclyl (C 1 -C 20 )alkyl, (C 1 -C 8 )alkyl (C 1 -C 6 )alkylamino (C 1 -C 6 )alkynyl, (C 1 -C 8 )alkylamino(C 1 -C 20 )alkanol or (C 1 -C 8 )alkylene Alkylamino(C 1 -C 20 )alkanol (C 1 -C 8 )alkyl-substituted (C 3 -C 20 )heteroaryl.

於另一方面，本發明係關於一種製備前述化合物之方法，該方法包括：(1)將式(II)化合物 其中：R2、R3、R4、R5及R6係各自獨立為氫；或 R2、R4、R5及R6係各自獨立為氫且R3為CH3；或R2、R3、R5及R6係各自獨立為氫且R4為CH3、F、Cl或Br；或R2、R5、R6係各自獨立為氫、R3為OCH3且R4為Cl；或R2、R4為Cl且R3、R5、R6係各自獨立為氫，與溴甲苯、碘甲烷、碘乙烷、2-溴丙烷或亞甲基環丙基溴於一鹼性溶液中於約室溫至約80℃下進行反應，以獲得式(III)化合物 其中：R1為CH3、CH2CH3、CH(CH3)2、CH2CH(CH3)2或苯甲基；且R2、R3、R4、R5及R6係各自獨立為氫；或R2、R4、R5及R6係各自獨立為氫且R3為CH3；或R2、R3、R5及R6係各自獨立為氫且R4為CH3、F、Cl或Br；或R2、R5、R6係各自獨立為氫、R3為OCH3且R4為Cl；或R2、R4為Cl且R3、R5、R6係各自獨立為氫；(2)將式(III)化合物與雙(三甲基矽基)胺基鋰及一溴(C1-C20)烷醇於四氫呋喃中在0℃下進行反應，以獲得式(I)化合物 其中：R1為CH3、CH2CH3、CH(CH3)2、CH2CH(CH3)2或苯甲基；R2、R3、R4、R5及R6係各自獨立為氫；或R2、R4、R5及R6係各自獨立為氫且R3為CH3；或R2、R3、R5及R6係各自獨立為氫且R4為CH3、F、Cl或Br；或R2、R5、R6係各自獨立為氫、R3為OCH3且R4為Cl；或R3為Cl且R4為OCH3或R2、R4為Cl且R3、R5、R6係各自獨立為氫；且R7為(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH或(CH2)15OH，(3)將其中R1為苯甲基的式(I)化合物，與氫氣於壓力下透過鈀碳在室溫下於甲醇中進行反應，或與三氯化硼於二氯甲烷中在0℃下進行反應，以獲得式(I)化合物 In another aspect, the invention relates to a process for the preparation of a compound of the foregoing, which process comprises: (1) a compound of formula (II) Wherein: R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; or R 2 , R 4 , R 5 and R 6 are each independently hydrogen and R 3 is CH 3 ; or R 2 , R 3 , R 5 and R 6 are each independently hydrogen and R 4 is CH 3 , F, Cl or Br; or R 2 , R 5 , R 6 are each independently hydrogen, R 3 is OCH 3 and R 4 is Cl; or R 2 , R 4 are Cl and R 3 , R 5 , R 6 are each independently hydrogen, with bromotoluene, methyl iodide, ethyl iodide, 2-bromopropane or methylene cyclopropyl bromide The reaction is carried out in an alkaline solution at a temperature of from about room temperature to about 80 ° C to obtain a compound of the formula (III) Wherein: R 1 is CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 or benzyl; and R 2 , R 3 , R 4 , R 5 and R 6 are each Independently hydrogen; or R 2 , R 4 , R 5 and R 6 are each independently hydrogen and R 3 is CH 3 ; or R 2 , R 3 , R 5 and R 6 are each independently hydrogen and R 4 is CH 3 , F, Cl or Br; or R 2 , R 5 , R 6 are each independently hydrogen, R 3 is OCH 3 and R 4 is Cl; or R 2 , R 4 are Cl and R 3 , R 5 , R 6 is each independently hydrogen; (2) reacting a compound of formula (III) with bis(trimethylsulfonyl)amino lithium and monobromo(C 1 -C 20 ) alkanol in tetrahydrofuran at 0 ° C, To obtain a compound of formula (I) Wherein: R 1 is CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 or benzyl; R 2 , R 3 , R 4 , R 5 and R 6 are each independently Is hydrogen; or R 2 , R 4 , R 5 and R 6 are each independently hydrogen and R 3 is CH 3 ; or R 2 , R 3 , R 5 and R 6 are each independently hydrogen and R 4 is CH 3 , F, Cl or Br; or R 2 , R 5 , R 6 are each independently hydrogen, R 3 is OCH 3 and R 4 is Cl; or R 3 is Cl and R 4 is OCH 3 or R 2 , R 4 Is Cl and R 3 , R 5 , R 6 are each independently hydrogen; and R 7 is (CH 2 ) 9 OH, (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, ( CH 2 ) 13 OH or (CH 2 ) 15 OH, (3) a compound of the formula (I) wherein R 1 is a benzyl group, reacted with hydrogen under pressure through palladium carbon at room temperature in methanol, or The reaction is carried out with boron trichloride in dichloromethane at 0 ° C to obtain a compound of formula (I)

R1、R2、R3、R4、R5及R6係各自獨立為氫；或R1、R2、R4、R5及R6係各自獨立為氫且R3為CH3；或R1、R2、R3、R5及R6係各自獨立為氫且R4為CH3、F、Cl或Br；或R1、R2、R5、R6係各自獨立為氫、R3為OCH3且R4為Cl；或R2、R4為Cl且R1、R3、R5、R6係各自獨立為氫；且R7為(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH或(CH2)15OH；或(4)將其中R1、R2、R3、R4、R5及R6係各自獨立為氫且R7為(CH2)11OH的式(I)化合物，與N-氯琥珀醯亞胺於氯甲烷中在室溫下進行反應，以提供式(I)化合物，其中R1、R3、R5及R6係各自獨立為氫、R2及R4係各自獨立為氯且R7為(CH2)11OH；或(5)將其中R1為甲基、R2、R3、R4、R5及R6係各自獨立為氫且R7為(CH2)11OH、(CH2)12OH或(CH2)13OH的式(1)化合物，與濃鹽酸、ICl3及冰乙酸進行反應，以提供式(I)化合物，其中R1為甲基、R2、R3、R5及R6係各自獨立為氫、R4為Cl且R7為(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH、(CH2)15OH、(CH2)10OCOCH3、(CH2)11OCOCH3、(CH2)12OCOCH3或(CH2)13OCOCH3；或(6)將2-胺基苯酚與甲基乙烯基酮於鹽酸中進行反應，以獲得式(INT-1)化合物 (7)將式(INT-1)化合物與碘甲烷、碘乙烷、2-溴丙烷、亞甲基環丙基溴或溴甲苯於鹼性溶液中進行反應，以提供式(III)化合物 其中R10為甲基、乙基、2-丙基、亞甲基環丙基或苯甲基；(8)將其中R10為甲基、乙基、2-丙基、亞甲基環丙基或苯甲基的式(III)化合物，與雙(三甲基矽基)胺基鋰及10-溴-1-癸醇或11-溴-1-十一醇於四氫呋喃中在0℃下進行反應，以獲得式(I)化合物，其中R1為甲基、乙基、2-丙基、亞甲基環丙基或苯甲基；R2、R3、R4、R6及R7係各自獨立為氫；且R5為(CH2)11OH或(CH2)12OH；(9)將其中R1為苯甲基；R2、R3、R4、R6及R7係各自獨立為氫；且R5為(CH2)11OH或(CH2)12OH的式(I)化合物，與氫氣於壓力下透過鈀碳在室溫下於甲醇中進行反應，以獲得式(I)化合物，其中R1為氫；R2、R3、R4、R6及R7係各自獨立為氫；且R5為(CH2)11OH或(CH2)12OH；或 (10)將2-三氟甲氧基苯胺與巴豆醛反應，以獲得2-甲基-8-三氟甲氧基喹啉，將其以雙(三甲基矽基)胺基鋰及一溴(C1-C20)烷醇於四氫呋喃中在0℃下進行處理，以獲得式(I)化合物，其中R1為三氟甲基；R2、R3、R4、R5及R6係各自獨立為氫；且R7為(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH或(CH2)15OH；或(11)將一式(IV)之8-羥基-2-甲基喹啉化合物，其中R1為氫、甲基、乙基、2-丙基或亞甲基環丙基 與二氧化硒於二【口+咢】烷中在升溫下進行反應，以提供一式(VI)化合物，R1為氫、甲基、乙基、2-丙基或亞甲基環丙基；以及 R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; or R 1 , R 2 , R 4 , R 5 and R 6 are each independently hydrogen and R 3 is CH 3 ; Or R 1 , R 2 , R 3 , R 5 and R 6 are each independently hydrogen and R 4 is CH 3 , F, Cl or Br; or R 1 , R 2 , R 5 , R 6 are each independently hydrogen. And R 3 is OCH 3 and R 4 is Cl; or R 2 and R 4 are Cl and R 1 , R 3 , R 5 , and R 6 are each independently hydrogen; and R 7 is (CH 2 ) 9 OH, ( CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH or (CH 2 ) 15 OH; or (4) wherein R 1 , R 2 , R 3 , R 4. A compound of formula (I) wherein R 5 and R 6 are each independently hydrogen and R 7 is (CH 2 ) 11 OH, reacted with N-chlorosuccinimide in methyl chloride at room temperature to provide a compound of formula (I), wherein R 1 , R 3 , R 5 and R 6 are each independently hydrogen, R 2 and R 4 are each independently chlorine and R 7 is (CH 2 ) 11 OH; or (5) Wherein R 1 is methyl, R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen and R 7 is (CH 2 ) 11 OH, (CH 2 ) 12 OH or (CH 2 ) 13 OH compound with concentrated hydrochloric acid, ICl 3 of glacial acetic acid and the reaction of formula (1), to provide compounds of formula (I) a compound wherein R 1 is methyl, R 2 , R 3 , R 5 and R 6 are each independently hydrogen, R 4 is Cl and R 7 is (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH, (CH 2 ) 15 OH, (CH 2 ) 10 OCOCH 3 , (CH 2 ) 11 OCOCH 3 , (CH 2 ) 12 OCOCH 3 or (CH 2 ) 13 OCOCH 3 Or (6) reacting 2-aminophenol with methyl vinyl ketone in hydrochloric acid to obtain a compound of formula (INT-1) (7) reacting a compound of the formula (INT-1) with methyl iodide, ethyl iodide, 2-bromopropane, methylene cyclopropyl bromide or bromine toluene in an alkaline solution to provide a compound of the formula (III) Wherein R 10 is methyl, ethyl, 2-propyl, methylenecyclopropyl or benzyl; (8) wherein R 10 is methyl, ethyl, 2-propyl, methylene cyclopropane Or a benzyl group of a compound of formula (III) with bis(trimethyldecyl)amine lithium and 10-bromo-1-nonanol or 11-bromo-1-undecyl alcohol in tetrahydrofuran at 0 ° C The reaction is carried out to obtain a compound of the formula (I) wherein R 1 is methyl, ethyl, 2-propyl, methylenecyclopropyl or benzyl; R 2 , R 3 , R 4 , R 6 and R 7 is each independently hydrogen; and R 5 is (CH 2 ) 11 OH or (CH 2 ) 12 OH; (9) wherein R 1 is benzyl; R 2 , R 3 , R 4 , R 6 and R 7 is a compound of formula (I) each independently being hydrogen; and R 5 is (CH 2 ) 11 OH or (CH 2 ) 12 OH, reacted with hydrogen under pressure through palladium on carbon at room temperature in methanol, A compound of formula (I) wherein R 1 is hydrogen; R 2 , R 3 , R 4 , R 6 and R 7 are each independently hydrogen; and R 5 is (CH 2 ) 11 OH or (CH 2 ) 12 OH Or (10) reacting 2-trifluoromethoxyaniline with crotonaldehyde to obtain 2-methyl-8-trifluoromethoxyquinoline, which is bis(trimethylsulfonyl)amine lithium bromine and a (C 1 -C 20) Ol in tetrahydrofuran at 0 ℃ treatment, to obtain a formula (I) compounds wherein R 1 is trifluoromethyl; R 2, R 3, R 4, R 5 and R 6 are each independently hydrogen lines; and R 7 is (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH or (CH 2 ) 15 OH; or (11) an 8-hydroxy group of the formula (IV) a -2-methylquinoline compound wherein R 1 is hydrogen, methyl, ethyl, 2-propyl or methylene cyclopropyl The reaction is carried out with selenium dioxide in dioxane at elevated temperature to provide a compound of formula (VI), R 1 being hydrogen, methyl, ethyl, 2-propyl or methylene cyclopropyl; as well as

(12)將其中R1為氫、甲基、乙基、2-丙基或亞甲基環丙基之式(VI)化合物，與N-甲基丙炔胺進行反應，以獲得一式(I)化合物，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2或CH(CH3)2、R2、R3、R4、R5及R6係各自獨立為氫；且R7為CH2N(CH3)CH2C≡CH；或 (13)將R1為氫、甲基、乙基、2-丙基或亞甲基環丙基的式(VI)化合物，與2(哌【口+井】-1-基)乙醇進行反應，以獲得一式(I)化合物，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2或CH(CH3)2、R2、R3、R4、R5及R6係各自獨立為氫；且R7為CH2(N(CH2CH2)2N)CH2CH2OH；或(14)將式(VI)化合物與一胺基(C1-C20)烷醇進行反應以獲得一式(I)化合物，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2或CH(CH3)2；R2、R3、R4、R5及R6係各自獨立為氫；且R7為CH2NH(CH2)8OH或CH2N((CH2)6OH)CH2(8-甲氧基喹啉-2-基)。 (12) reacting a compound of the formula (VI) wherein R 1 is hydrogen, methyl, ethyl, 2-propyl or methylenecyclopropyl, with N-methylpropynylamine to obtain one formula (I) a compound wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 or CH(CH 3 ) 2 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; and R 7 is CH 2 N(CH 3 )CH 2 C≡CH; or (13) R 1 is hydrogen, methyl, ethyl, 2-propyl or A methylene cyclopropyl compound of the formula (VI) is reacted with 2 (piperider + well)-1-yl)ethanol to obtain a compound of the formula (I) wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 or CH(CH 3 ) 2 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; and R 7 is CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 2 OH; or (14) reacting a compound of the formula (VI) with an amine (C 1 -C 20 ) alkanol to obtain a formula ( I) a compound wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 or CH(CH 3 ) 2 ; R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; and R 7 is CH 2 NH(CH 2 ) 8 OH or CH 2 N((CH 2 ) 6 OH) CH 2 (8-methoxyquinolin-2-yl).

於另一方面，本發明係關於一種組成物，其包括一治療有效量之前述化合物或其醫藥可接受性鹽類、溶劑化物或水合物、前藥或代謝物，以及一醫藥可接受性稀釋劑或載劑。 In another aspect, the invention relates to a composition comprising a therapeutically effective amount of a compound of the foregoing, or a pharmaceutically acceptable salt, solvate or hydrate thereof, prodrug or metabolite thereof, and a pharmaceutically acceptable dilution Agent or carrier.

於又一方面，本發明係關於一種組成物，其包括一前述化合物或其醫藥可接受性鹽類、溶劑化物或水合物、前藥或代謝物，以及一醫藥可接受性稀釋劑或載劑，可用於治療一神經退化性疾病。 In still another aspect, the present invention relates to a composition comprising a compound of the foregoing, or a pharmaceutically acceptable salt, solvate or hydrate thereof, prodrug or metabolite thereof, and a pharmaceutically acceptable diluent or carrier It can be used to treat a neurodegenerative disease.

於再一方面，本發明係關於一種前述化合物用於製備神經退化性疾病治療用藥物的用途。於一實施例中，該藥物係用於治療阿茲海默症。 In still another aspect, the present invention relates to the use of a compound as described above for the manufacture of a medicament for the treatment of a neurodegenerative disease. In one embodiment, the drug is for the treatment of Alzheimer's disease.

這些及其他方面將可透過以下較佳具體實施例之說明配合下列圖式而有所了解，然而在不背離本發明之新穎概念的精神與範圍下可進行變化及修改。 These and other aspects will be understood by the following description of the preferred embodiments of the present invention, which may be modified and modified without departing from the spirit and scope of the invention.

附隨之圖式說明一或多種本發明具體實施例，配合發明說明可闡明本發明之原理。若有可能，相同之參考編號係用於全部圖式以表示具體實施例之相同或類似元件。 The accompanying drawings illustrate one or more embodiments of the invention, Wherever possible, the same reference numerals are in the

圖1A-B顯示化合物C12於鋅離子存在或不存在之條件下對於fAβ形成及fAβs分離之影響的形態分析。 1A-B show morphological analysis of the effect of compound C12 on fAβ formation and fAβs separation in the presence or absence of zinc ions.

圖2顯示化合物C12在鋅離子不存在下抑制Aβ之聚合作用。 Figure 2 shows that compound C12 inhibits the polymerization of Aβ in the absence of zinc ions.

圖3A-B顯示化合物C12作為針對fAβ之神經保護劑。 Figures 3A-B show compound C12 as a neuroprotective against fAβ.

圖4顯示喹啉衍生物誘發的軸突生長。 Figure 4 shows axonal derivative induced axonal growth.

圖5顯示喹啉衍生物增加GAP43(軸突生長之標記物)之表現。 Figure 5 shows the performance of quinoline derivatives increasing GAP43, a marker for axon growth.

圖6顯示滾輪試驗的結果。 Figure 6 shows the results of the roller test.

圖7A-D顯示Morris水迷宮試驗的結果。 Figures 7A-D show the results of the Morris water maze test.

圖8顯示於化合物C12治療後，在記憶障礙fAβ病變小鼠中GAP43增加及fAβ減少。 Figure 8 shows an increase in GAP43 and a decrease in fAβ in mice with memory impairment fAβ lesions after treatment with compound C12.

除非前後文有清楚指明，否則單數形式的「一」及「該」包含複數的情形。 The singular forms "a" and "the" are used in the plural unless they are clearly indicated.

不在兩個字母或符號間的破折號「-」係用以表示一部分或取代基的連接點。舉例而言，-CONH2部分係透過碳原子連接。 A dash "-" that is not between two letters or symbols is used to indicate a part or a point of attachment of a substituent. For example, the -CONH 2 moiety is attached through a carbon atom.

術語「胺基」表示-NH2。胺基可任意經取代，如本文對於術語「經取代」之定義。術語「烷基胺基」表示-NR2，其中至少一個R為烷基而第二個R 為烷基或氫。術語「醯基胺基」表示N(R)C(=O)R，其中各R獨立為氫、烷基或芳基。 The term "amino" means -NH 2 . The amine group can be optionally substituted as defined herein for the term "substituted." The term "alkylamino" denotes -NR 2 wherein at least one R is alkyl and the second R is alkyl or hydrogen. The term "mercaptoamine" means N(R)C(=O)R, wherein each R is independently hydrogen, alkyl or aryl.

術語「烷基」表示含正鏈、二級、三級或環碳原子之C1-C18烴。實例為甲基、乙基、1-丙基、2-丙基、1-丁基、2-甲基-1-丙基(異丁基，-CH2CH(CH3)2)、2-丁基(第二丁基，-CH(CH3)CH2CH3)、2-甲基-2-丙基(第三丁基，-C(CH3)3)、1-戊基、2-戊基、3-戊基、2-甲基-2-丁基、3-甲基-2-丁基、3-甲基-1-丁基、2-甲基-1-丁基、1-己基、2-己基、3-己基、2-甲基-2-戊基、3-甲基-2-戊基、4-甲基-2-戊基、3-甲基-3-戊基、2-甲基-3-戊基、2,3-二甲基-2-丁基、3,3-二甲基-2-丁基。烷基可為單價烴基團，如上所述及例示，或其可為二價烴基團(即伸烷基)。該烷基可任意經一或多個下列基團取代：烷氧基、鹵基、鹵烷基、羥基、羥基烷基、芳基、雜芳基、雜環、環烷基、烷醯基、烷氧基羰基、胺基、亞胺基、烷基胺基、醯基胺基、硝基、三氟甲基、三氟甲氧基、羧基、羧基烷基、酮基、硫酮基、烷硫基、烷基亞磺醯基、烷基磺醯基、氰基、乙醯胺基、乙醯氧基、乙醯基、苯甲醯胺基、苯亞磺醯基、苯磺醯胺基、苯磺醯基、苯磺醯基胺基、苯甲醯基、苯甲醯基胺基、苯甲醯氧基、苯甲基、苯甲氧基、苯甲氧基羰基、苯甲基硫基、胺甲醯基、胺甲酸基、異氰酸基(isocyannato)、胺磺醯基、胺亞磺醯基、亞磺酸基、磺酸基、磺酸胺基、硫代磺酸基、NRxRy及/或COORx，其中各Rx及Ry獨立為H、烷基、烯基、芳基、雜芳基、雜環、環烷基或羥基。該烷基可任意以一或多個非過氧化氧基(-O-)、硫基(-S-)、胺基(-N(H)-)、亞甲基二氧基(-OCH2O-)、羰基(-C(=O)-)、羧基(-C(=O)O-)、羰基二氧基(-OC(=O)O-)、羧根基(-OC(=O)-)、亞胺基 (C=NH)、亞磺醯基(SO)或磺醯基(SO2)中斷。此外，該烷基可任意為至少部分未飽和，因此提供一種烯基。 The term "alkyl" denotes a C 1 -C 18 hydrocarbon containing a normal, secondary, tertiary or cyclic carbon atom. Examples are methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-methyl-1-propyl (isobutyl, -CH 2 CH(CH 3 ) 2 ), 2- Butyl (t-butyl, -CH(CH 3 )CH 2 CH 3 ), 2-methyl-2-propyl (t-butyl, -C(CH 3 ) 3 ), 1-pentyl, 2 -pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1 -hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl. The alkyl group can be a monovalent hydrocarbon group, as described and exemplified above, or it can be a divalent hydrocarbon group (ie, an alkylene group). The alkyl group may be optionally substituted by one or more of the following groups: alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, alkanoyl, Alkoxycarbonyl, amine, imino, alkylamino, decylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, thiol, alkane Thio group, alkylsulfinyl group, alkylsulfonyl group, cyano group, etidinyl group, ethoxylated group, ethoxylated group, benzammonium group, phenylsulfinyl group, benzenesulfonylamino group , phenylsulfonyl, phenylsulfonylamino, benzhydryl, benzhydrylamino, benzhydryloxy, benzyl, benzyloxy, benzyloxycarbonyl, benzyl sulfide Base, amine methyl sulfhydryl, amine carboxylic acid group, isocyannato, amine sulfonyl group, amine sulfinyl group, sulfinic acid group, sulfonic acid group, sulfonic acid amine group, thiosulfonic acid group, NR x R y and/or COOR x , wherein each R x and R y is independently H, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl or hydroxy. The alkyl group may optionally be one or more of a non-peroxyoxy group (-O-), a thio group (-S-), an amine group (-N(H)-), a methylenedioxy group (-OCH 2 ). O-), carbonyl (-C(=O)-), carboxyl (-C(=O)O-), carbonyldioxy (-OC(=O)O-), carboxy root (-OC(=O) )-), imino group (C=NH), sulfinyl (SO) or sulfonyl (SO 2 ) is interrupted. Furthermore, the alkyl group can be optionally at least partially unsaturated, thus providing an alkenyl group.

術語「伸烷基」表示一種1-18個碳原子的飽和、支鏈或直鏈或環狀烴基團，且具有由母烷類之相同或不同碳原子上移除兩個氫原子而衍生的兩個單價基團中心。典型伸烷基基團包括但不限於亞甲基(-CH2-)、1,2-伸乙基(CH2CH2-)、1,3-伸丙基(-CH2CH2CH2-)、1,4-伸丁基(CH2CH2CH2CH2-)等等。該伸烷基可任意經一或多個下列基團取代：烷氧基、鹵基、鹵烷基、羥基、羥基烷基、芳基、雜芳基、雜環、環烷基、烷醯基、烷氧基羰基、胺基、亞胺基、烷基胺基、醯基胺基、硝基、三氟甲基、三氟甲氧基、羧基、羧基烷基、酮基、硫酮基、烷硫基、烷基亞磺醯基、烷基磺醯基、氰基、乙醯胺基、乙醯氧基、乙醯基、苯甲醯胺基、苯亞磺醯基、苯磺醯胺基、苯磺醯基、苯磺醯基胺基、苯甲醯基、苯甲醯基胺基、苯甲醯氧基、苯甲基、苯甲氧基、苯甲氧基羰基、苯甲基硫基、胺甲醯基、胺甲酸基、異氰酸基、胺磺醯基、胺亞磺醯基、亞磺酸基、磺酸基、磺酸胺基、硫代磺酸基、NRxRy及/或COORx，其中各Rx及Ry獨立為H、烷基、烯基、芳基、雜芳基、雜環、環烷基或羥基。此外，該伸烷基可任意以一或多個非過氧化氧基(-O-)、硫基(-S-)、胺基(-N(H)-)、亞甲基二氧基(-OCH2O-)、羰基(-C(=O)-)、羧基(-C(=O)O-)、羰基二氧基(-OC(=O)O-)、羧根基(-OC(=O)-)、亞胺(C=NH)、亞磺醯基(SO)或磺醯基(SO2)中斷。此外，該伸烷基可任意為至少部分未飽和，因此提供一種伸烯基。 The term "alkylene" means a saturated, branched or straight-chain or cyclic hydrocarbon group of 1 to 18 carbon atoms and derived from the removal of two hydrogen atoms from the same or different carbon atoms of the parent alkane. Two monovalent group centers. Typical alkylene groups include, but are not limited to, methylene (-CH 2 -), 1,2-extended ethyl (CH 2 CH 2 -), 1,3-propenyl (-CH 2 CH 2 CH 2 -), 1,4-tert-butyl (CH 2 CH 2 CH 2 CH 2 -), and the like. The alkylene group may be optionally substituted by one or more of the following groups: alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, alkanoyl , alkoxycarbonyl, amine, imine, alkylamino, decylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, thiol, Alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, etidinyl, ethoxylated, ethoxylated, benzylamino, phenylsulfinyl, benzenesulfonamide Base, benzenesulfonyl, benzenesulfonylamino, benzhydryl, benzhydrylamino, benzhydryloxy, benzyl, benzyloxy, benzyloxycarbonyl, benzyl Thio group, amine methyl sulfhydryl group, urethane group, isocyanate group, amine sulfonyl group, amine sulfinylene group, sulfinic acid group, sulfonic acid group, sulfonic acid amine group, thiosulfonic acid group, NR x R y and/or COOR x , wherein each R x and R y is independently H, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl or hydroxy. Further, the alkylene group may optionally be one or more of a non-peroxyoxy group (-O-), a thio group (-S-), an amine group (-N(H)-), or a methylenedioxy group ( -OCH 2 O-), carbonyl (-C(=O)-), carboxyl (-C(=O)O-), carbonyldioxy (-OC(=O)O-), carboxylate (-OC (=O)-), imine (C=NH), sulfinyl (SO) or sulfonyl (SO 2 ) interrupted. Furthermore, the alkylene group can be optionally at least partially unsaturated, thus providing an extended alkenyl group.

術語「炔基」表示一種單基團支鏈或無支鏈之烴鏈，其具有一完全未飽和部分(即一碳-碳sp參鍵)。於一具體實施例中，炔基可具有2至10個碳 原子，或2至6個碳原子。於另一具體實施例中，炔基可具有2至4個碳原子。此術語可由以下基團例示：乙炔基、1-丙炔基、2-丙炔基、1-丁炔基、2-丁炔基、3-丁炔基、1-己炔基、2-己炔基、3-己炔基、1-辛炔基等等。炔基可為經取代或未經取代者。 The term "alkynyl" means a mono-branched or unbranched hydrocarbon chain having a fully unsaturated moiety (i.e., a carbon-carbon sp- bond). In a particular embodiment, an alkynyl group can have from 2 to 10 carbon atoms, or from 2 to 6 carbon atoms. In another embodiment, an alkynyl group can have from 2 to 4 carbon atoms. This term can be exemplified by ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-hexynyl, 2-hexyl Alkynyl, 3-hexynyl, 1-octynyl and the like. An alkynyl group can be substituted or unsubstituted.

術語「烷氧基」表示烷基-O-之基團，其中烷基如本文之定義。較佳之烷氧基包括例如甲氧基、乙氧基、正丙氧基、異丙氧基、正丁氧基、第三丁氧基、第二丁氧基、正戊氧基、正己氧基、1,2-二甲基丁氧基等。烷氧基可任意經一或多個下列基團取代：鹵基、鹵烷基、羥基、羥基烷基、芳基、雜芳基、雜環、環烷基、烷醯基、烷氧基羰基、胺基、亞胺基、烷基胺基、醯基胺基、硝基、三氟甲基、三氟甲氧基、羧基、羧基烷基、酮基、硫酮基、烷硫基、烷基亞磺醯基、烷基磺醯基、氰基、乙醯胺基、乙醯氧基、乙醯基、苯甲醯胺基、苯亞磺醯基、苯磺醯胺基、苯磺醯基、苯磺醯基胺基、苯甲醯基、苯甲醯基胺基、苯甲醯氧基、苯甲基、苯甲氧基、苯甲氧基羰基、苯甲基硫基、胺甲醯基、胺甲酸基、異氰酸基、胺磺醯基、胺亞磺醯基、亞磺酸基、磺酸基、磺酸胺基、硫代磺酸基、NRxRy及/或COORx，其中各Rx及Ry獨立為H、烷基、烯基、芳基、雜芳基、雜環、環烷基或羥基。 The term "alkoxy" denotes an alkyl-O- group wherein alkyl is as defined herein. Preferred alkoxy groups include, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, second butoxy, n-pentyloxy, n-hexyloxy 1,2-dimethylbutoxy and the like. The alkoxy group may be optionally substituted by one or more of the following groups: halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocyclic, cycloalkyl, alkanoyl, alkoxycarbonyl , amine, imido, alkylamino, decylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, thioketo, alkylthio, alkane A sulfinyl group, an alkylsulfonyl group, a cyano group, an etidinyl group, an ethoxylated group, an ethyl fluorenyl group, a benzamidine group, a sulfinyl group, a benzenesulfonyl group, a benzenesulfonate Base, benzenesulfonylamino, benzhydryl, benzhydrylamino, benzhydryloxy, benzyl, benzyloxy, benzyloxycarbonyl, benzylthio, amine Sulfhydryl, urethane, isocyanate, amidoxime, amine sulfoximine, sulfinate, sulfonate, sulfonate, thiosulfonate, NR x R y and/or COOR x wherein each R x and R y is independently H, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl or hydroxy.

術語「烷醇」表示通式ROH之化合物，其中R為烷基，其定義如上。 The term "alkanol" means a compound of the formula ROH wherein R is alkyl and is as defined above.

術語「芳基」表示具有單環(例如苯基)或多個縮合(稠合)環的6至20個碳原子之未飽和芳族碳環基團，其中至少一環為芳族環 (例如萘基、二氫菲基、茀基或蒽基)。較佳之芳基包括苯基、萘基等。該芳基可任意為二價基團，因而提供一種伸芳基。芳基可任意經一或多個下列基團取代：烷基、烯基、烷氧基、鹵基、鹵烷基、羥基、羥基烷基、芳基、雜芳基、雜環、環烷基、烷醯基、烷氧基羰基、胺基、亞胺基、烷基胺基、醯基胺基、硝基、三氟甲基、三氟甲氧基、羧基、羧基烷基、酮基、硫酮基、烷硫基、烷基亞磺醯基、烷基磺醯基、氰基、乙醯胺基、乙醯氧基、乙醯基、苯甲醯胺基、苯亞磺醯基、苯磺醯胺基、苯磺醯基、苯磺醯基胺基、苯甲醯基、苯甲醯基胺基、苯甲醯氧基、苯甲基、苯甲氧基、苯甲氧基羰基、苯甲基硫基、胺甲醯基、胺甲酸基、異氰酸基、胺磺醯基、胺亞磺醯基、亞磺酸基、磺酸基、磺酸胺基、硫代磺酸基、NRxRy及/或COORx，其中各Rx及Ry獨立為H、烷基、烯基、芳基、雜芳基、雜環、環烷基或羥基。 The term "aryl" denotes an unsaturated aromatic carbocyclic group of 6 to 20 carbon atoms having a single ring (e.g., phenyl) or a plurality of condensed (fused) rings, wherein at least one ring is an aromatic ring (e.g., naphthalene). Base, dihydrophenanthrenyl, anthracenyl or fluorenyl). Preferred aryl groups include phenyl, naphthyl and the like. The aryl group may be optionally a divalent group, thus providing an extended aryl group. The aryl group may be optionally substituted by one or more of the following groups: alkyl, alkenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocyclic, cycloalkyl , alkanoyl, alkoxycarbonyl, amine, imine, alkylamino, decylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, a thioketo group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, a cyano group, an etidinyl group, an ethoxylated group, an ethyl fluorenyl group, a benzamidine group, a phenyl sulfinyl group, Phenylsulfonylamino, phenylsulfonyl, phenylsulfonylamino, benzhydryl, benzhydrylamino, benzhydryloxy, benzyl, benzyloxy, benzyloxycarbonyl , benzylthio, amine, mercapto, carboxylic acid, isocyanate, amidoxime, amine sulfinyl, sulfinate, sulfonate, sulfonate, thiosulfonic acid a group, NR x R y and/or COOR x , wherein each R x and R y is independently H, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl or hydroxy.

術語「芳氧基」及「芳基烷氧基」各表示鍵結至氧原子之芳基以及在烷基部分鍵結至氧原子之芳烷基。實例包括但不限於苯氧基、萘氧基及苯甲氧基。 The terms "aryloxy" and "arylalkoxy" each denote an aryl group bonded to an oxygen atom and an aralkyl group bonded to an oxygen atom at the alkyl moiety. Examples include, but are not limited to, phenoxy, naphthyloxy, and benzyloxy.

術語「碳環」表示飽和、未飽和或芳族環，其具有3至8個碳原子為單環，7至12個碳原子為雙環，而至多約30個碳原子為多環。單環碳環一般具有3至6個環原子，更典型為5或6個環原子。雙環碳環具有7至12個環原子，例如排列為雙環[4,5]、[5,5]、[5,6]或[6,6]系統，或9或10個環原子排列為雙環[5,6]或[6,6]系統。碳環之實例包括環丙基、環丁基、環戊基、1-環戊-1-烯基、1-環戊-2-烯 基、1-環戊-3-烯基、環己基、1-環己-1-烯基、1-環己-2-烯基、1-環己-3-烯基、苯基、螺環基及萘基。該碳環可任意經上述可取代烷基之基團取代。 The term "carbocycle" means a saturated, unsaturated or aromatic ring having from 3 to 8 carbon atoms which is a monocyclic ring, from 7 to 12 carbon atoms being a bicyclic ring, and up to about 30 carbon atoms being a polycyclic ring. Monocyclic carbocycles typically have from 3 to 6 ring atoms, more typically 5 or 6 ring atoms. Bicyclic carbocycles having from 7 to 12 ring atoms, for example arranged in a bicyclo[4,5], [5,5], [5,6] or [6,6] system, or 9 or 10 ring atoms arranged in a double ring [5,6] or [6,6] system. Examples of the carbocyclic ring include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a 1-cyclopent-1-enyl group, and a 1-cyclopent-2-ene. , 1-cyclopent-3-enyl, cyclohexyl, 1-cyclohex-1-enyl, 1-cyclohex-2-enyl, 1-cyclohex-3-enyl, phenyl, spiro Base and naphthyl. The carbocyclic ring may be optionally substituted with a group of the above-mentioned substitutable alkyl group.

若一取代基被指定為所指定者的一或多個原子，「或一鍵」時，在該取代基為「一鍵」所代表的組態中，緊鄰所指定取代基的基團係透過化學上合理的鍵結組態彼此直接連接。 If a substituent is specified as one or more atoms of the specified one, "or one-key", in the configuration represented by the "one-bond" substituent, the group immediately adjacent to the specified substituent is transmitted through The chemically sound bond configurations are directly connected to each other.

術語「環烷基」表示3至20個碳原子之環狀烷基，其具有單環或多環縮合環。此環烷基包括，舉例而言，單環結構例如為環丙基、環丁基、環戊基、環辛基等，或多環結構例如為金剛烷基等。環烷基可任意經一或多個下列基團取代：烷基、烯基、烷氧基、鹵基、鹵烷基、羥基、羥基烷基、芳基、雜芳基、雜環、環烷基、烷醯基、烷氧基羰基、胺基、亞胺基、烷基胺基、醯基胺基、硝基、三氟甲基、三氟甲氧基、羧基、羧基烷基、酮基、硫酮基、烷硫基、烷基亞磺醯基、烷基磺醯基、氰基、乙醯胺基、乙醯氧基、乙醯基、苯甲醯胺基、苯亞磺醯基、苯磺醯胺基、苯磺醯基、苯磺醯基胺基、苯甲醯基、苯甲醯基胺基、苯甲醯氧基、苯甲基、苯甲氧基、苯甲氧基羰基、苯甲基硫基、胺甲醯基、胺甲酸基、異氰酸基、胺磺醯基、胺亞磺醯基、亞磺酸基、磺酸基、磺酸胺基、硫代磺酸基、NRxRy及/或COORx，其中各Rx及Ry獨立為H、烷基、烯基、芳基、雜芳基、雜環、環烷基或羥基。環烷基可任意為至少部分未飽和，因而提供一種環烯基。此外，環烷基可任意為二價基團，因而提供一種伸環烷基。 The term "cycloalkyl" denotes a cyclic alkyl group of 3 to 20 carbon atoms which has a monocyclic or polycyclic fused ring. The cycloalkyl group includes, for example, a monocyclic structure such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclooctyl group or the like, or a polycyclic structure such as an adamantyl group or the like. The cycloalkyl group may be optionally substituted by one or more of the following groups: alkyl, alkenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkane Alkyl, alkoxycarbonyl, alkoxycarbonyl, amine, imido, alkylamino, decylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto , thioketo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, etidinyl, ethoxylated, ethoxylated, benzylamino, phenylsulfinyl , benzenesulfonamide, benzenesulfonyl, benzenesulfonylamino, benzhydryl, benzhydrylamino, benzhydryloxy, benzyl, benzyloxy, benzyloxy Carbonyl, benzylthio, aminemethanyl, urethane, isocyanate, amidoxime, amine sulfinyl, sulfinate, sulfonate, sulfonate, thiosulfonate An acid group, NR x R y and/or COOR x , wherein each R x and R y is independently H, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl or hydroxy. The cycloalkyl group can be optionally at least partially unsaturated, thus providing a cycloalkenyl group. Further, the cycloalkyl group may be optionally a divalent group, thus providing a stretched cycloalkyl group.

術語「有效量」表示足以產生有利或所欲結果之數量。特定投藥的有效量為熟悉醫藥技術者所能確定。 The term "effective amount" means an amount sufficient to produce a desired or desired result. The effective amount of a particular administration can be determined by those skilled in the art.

術語「鹵基」表示氟基、氯基、溴基及碘基。相同地，術語「鹵素」表示氟、氯、溴及碘。 The term "halo" means fluoro, chloro, bromo and iodo. Similarly, the term "halogen" means fluoro, chloro, bromo and iodo.

術語「鹵烷基」表示經1-4個鹵基取代之烷基，各鹵基可相同或相異。代表性之鹵烷基包括三氟甲基、3-氟十二烷基、12,12,12-三氟十二烷基、2-溴辛基、3-溴-6-氯庚基等。 The term "haloalkyl" denotes an alkyl group substituted with 1-4 halo groups, each halo group being the same or different. Representative haloalkyl groups include trifluoromethyl, 3-fluorododecyl, 12,12,12-trifluorododecyl, 2-bromooctyl, 3-bromo-6-chloroheptyl and the like.

術語「雜芳基」為含一、二或三個芳族環且在芳族環中含至少一氮、氧或硫原子之單環、雙環或三環系統，且其可為未經取代或經取代者。雜芳基可任意為二價基團，因而提供一伸雜芳基。雜芳基之實例包括但不限於2H-吡咯基、3H-吲哚基、4H-喹【口+井】基、4H-咔唑基、吖啶基、苯并[b]噻吩基、苯并噻唑基、β-咔啉基、咔唑基、【口+克】烯基、【口+辛】啉基(cinnaolinyl)、二苯并[b,d]呋喃基、呋呫基、呋喃基、咪唑基(imidazolyl)、咪唑基(imidizolyl)、吲唑基、吲【口+巾】基(indolisinyl)、吲哚基、異苯并呋喃基、異吲哚基、異喹啉基、異噻唑基、異【口+咢】唑基、【口+奈】啶基、萘[2,3-b]、【口+咢】唑基、呸啶基、啡啶基、啡啉基、啡砷【口+井】基、啡【口+井】基、啡噻【口+井】基、啡【口+咢】噻基、啡【口+咢】【口+井】基、呔【口+井】基、喋啶基、嘌呤基、哌喃基、吡【口+井】基、吡唑基、嗒【口+井】基、吡啶基、嘧啶基、吡咯基、喹唑啉基、喹啉基、喹【口+咢】啉基、噻二唑基、噻嗯基、噻唑基、噻吩基、三唑基及【口+山】基。在一具體實施例中，術語「雜芳基」 表示含有五或六個環原子之單環芳族環，並含碳及1、2、3或4個獨立選自非過氧化氧、硫及N(Z)之雜原子，其中Z不存在或為H、O、烷基、苯基或苯甲基。在另一具體實施例中，雜芳基表示約八至十個由其衍生之環原子之鄰-稠合雙環雜環，特別是苯-衍生物或由稠合伸丙基或伸丁基雙基團所衍生者。 The term "heteroaryl" is a monocyclic, bicyclic or tricyclic ring system containing one, two or three aromatic rings and containing at least one nitrogen, oxygen or sulfur atom in the aromatic ring, and which may be unsubstituted or Replaced by. The heteroaryl group may be optionally a divalent group, thus providing a heteroaryl group. Examples of heteroaryl groups include, but are not limited to, 2 H -pyrrolyl, 3 H -indolyl, 4 H -quino[indolyl], 4 H -carbazolyl, acridinyl, benzo[ b ]thiophene Base, benzothiazolyl, β-carboline, carbazolyl, [mouth + gram] alkenyl, [mouth + octyl] cinnaolinyl, dibenzo [b, d] furanyl, furazyl , furanyl, imidazolyl, imidizolyl, carbazolyl, indolisinyl, fluorenyl, isobenzofuranyl, isodecyl, isoquinolyl , isothiazolyl, iso [mouth + oxime] oxazolyl, [mouth + nai] pyridine, naphthalene [2,3- b ], [mouth + oxime] oxazolyl, acridinyl, phenanthryl, morpholinyl , arsenic arsenic [mouth + well] base, brown [mouth + well] base, morphine [mouth + well] base, brown [mouth + 咢] thiol, brown [mouth + 咢] [mouth + well] base, 呔[mouth + well] base, acridinyl, sulfhydryl, piperidyl, pyridyl], pyrazolyl, pyrene, pyridyl, pyrrolyl, quinazoline Base, quinolyl, quinol [mouth + fluorene] phenyl, thiadiazolyl, thiol, thiazolyl, thienyl, triazolyl and [mouth + ] Base. In one embodiment, the term "heteroaryl" means a monocyclic aromatic ring containing five or six ring atoms and contains carbon and 1, 2, 3 or 4 independently selected from the group consisting of non-peroxygen peroxide, sulfur and A hetero atom of N(Z) wherein Z is absent or is H, O, alkyl, phenyl or benzyl. In another embodiment, a heteroaryl group represents about eight to ten ortho-fused bicyclic heterocycles derived from a ring atom derived therefrom, particularly a benzene-derivative or a fused propyl or butyl group. The group is derived from.

雜芳基可任意經一或多個下列基團取代：烷基、烯基、烷氧基、鹵基、鹵烷基、羥基、羥基烷基、芳基、雜芳基、雜環、環烷基、烷醯基、烷氧基羰基、胺基、亞胺基、烷基胺基、醯基胺基、硝基、三氟甲基、三氟甲氧基、羧基、羧基烷基、酮基、硫酮基、烷硫基、烷基亞磺醯基、烷基磺醯基、氰基、乙醯胺基、乙醯氧基、乙醯基、苯甲醯胺基、苯亞磺醯基、苯磺醯胺基、苯磺醯基、苯磺醯基胺基、苯甲醯基、苯甲醯基胺基、苯甲醯氧基、苯甲基、苯甲氧基、苯甲氧基羰基、苯甲基硫基、胺甲醯基、胺甲酸基、異氰酸基、胺磺醯基、胺亞磺醯基、亞磺酸基、磺酸基、磺酸胺基、硫代磺酸基、NRxRy及/或COORx，其中各Rx及Ry獨立為H、烷基、烯基、芳基、雜芳基、雜環、環烷基或羥基。 The heteroaryl group may be optionally substituted by one or more of the following groups: alkyl, alkenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle, cycloalkane Alkyl, alkoxycarbonyl, alkoxycarbonyl, amine, imido, alkylamino, decylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto , thioketo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, etidinyl, ethoxylated, ethoxylated, benzylamino, phenylsulfinyl , benzenesulfonamide, benzenesulfonyl, benzenesulfonylamino, benzhydryl, benzhydrylamino, benzhydryloxy, benzyl, benzyloxy, benzyloxy Carbonyl, benzylthio, aminemethanyl, urethane, isocyanate, amidoxime, amine sulfinyl, sulfinate, sulfonate, sulfonate, thiosulfonate An acid group, NR x R y and/or COOR x , wherein each R x and R y is independently H, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl or hydroxy.

術語「雜環」或「雜環基」表示一飽和或部分未飽和之環系統，其含有至少一個選自氧、氮及硫之雜原子，且任意經烷基或C(=O)ORb取代，其中Rb為氫或烷基。典型之雜環為含有一或多個選自氧、氮及硫之雜原子的單環、雙環或三環基團。雜環基亦可含有連接至該環的酮基(=O)。雜環基之非限制性實例包括1,3-二氫苯并呋喃、1,3-二氧戊環、1,4-二【口+咢】烷、1,4-二噻【口+山】、2H- 哌喃、2-吡唑啉、4H-哌喃、【口+克】基、咪唑啶基、咪唑啉基、吲哚啉基、異【口+克】基、異吲哚啉基、嗎啉、哌【口+井】基、哌啶、哌啶基、吡唑啶、吡唑啶基、吡唑啉基、吡咯啶、吡咯啉、【口+昆】啶及硫代嗎啉。該雜環基可任意為二價基團，因而提供一伸雜環基。雜環可任意經一或多個下列基團取代：烷基、烯基、烷氧基、鹵基、鹵烷基、羥基、羥基烷基、芳基、雜芳基、雜環、環烷基、烷醯基、烷氧基羰基、胺基、亞胺基、烷基胺基、醯基胺基、硝基、三氟甲基、三氟甲氧基、羧基、羧基烷基、酮基、硫酮基、烷硫基、烷基亞磺醯基、烷基磺醯基、氰基、乙醯胺基、乙醯氧基、乙醯基、苯甲醯胺基、苯亞磺醯基、苯磺醯胺基、苯磺醯基、苯磺醯基胺基、苯甲醯基、苯甲醯基胺基、苯甲醯氧基、苯甲基、苯甲氧基、苯甲氧基羰基、苯甲基硫基、胺甲醯基、胺甲酸基、異氰酸基、胺磺醯基、胺亞磺醯基、亞磺酸基、磺酸基、磺酸胺基、硫代磺酸基、NRxRy及/或COORx，其中各Rx及Ry獨立為H、烷基、烯基、芳基、雜芳基、雜環、環烷基或羥基。 The term "heterocycle" or "heterocyclyl" denotes a saturated or partially unsaturated ring system containing at least one heteroatom selected from the group consisting of oxygen, nitrogen and sulfur, and optionally via alkyl or C(=O)OR b Substituted wherein R b is hydrogen or alkyl. Typical heterocycles are monocyclic, bicyclic or tricyclic groups containing one or more heteroatoms selected from the group consisting of oxygen, nitrogen and sulfur. The heterocyclic group may also contain a keto group (=O) attached to the ring. Non-limiting examples of heterocyclic groups include 1,3-dihydrobenzofuran, 1,3-dioxolane, 1,4-bis[oral+咢]alkane, 1,4-dithia [mouth+mountain 】, 2 H -pyran, 2-pyrazoline, 4 H -pyran, [mouth + gram] group, imidazolidinyl group, imidazolinyl group, porphyrin group, iso [mouth + gram] group, isoindole Porphyrin, morpholine, piperazine, piperidine, piperidinyl, pyrazolidine, pyrazolyl, pyrazolinyl, pyrrolidine, pyrroline, sulphonate Daimorpholine. The heterocyclic group may be optionally a divalent group, thereby providing a heterocyclic group. The heterocyclic ring may be optionally substituted by one or more of the following groups: alkyl, alkenyl, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocyclic, cycloalkyl , alkanoyl, alkoxycarbonyl, amine, imine, alkylamino, decylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxy, carboxyalkyl, keto, a thioketo group, an alkylthio group, an alkylsulfinyl group, an alkylsulfonyl group, a cyano group, an etidinyl group, an ethoxylated group, an ethyl fluorenyl group, a benzamidine group, a phenyl sulfinyl group, Phenylsulfonylamino, phenylsulfonyl, phenylsulfonylamino, benzhydryl, benzhydrylamino, benzhydryloxy, benzyl, benzyloxy, benzyloxycarbonyl , benzylthio, amine, mercapto, carboxylic acid, isocyanate, amidoxime, amine sulfinyl, sulfinate, sulfonate, sulfonate, thiosulfonic acid a group, NR x R y and/or COOR x , wherein each R x and R y is independently H, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl or hydroxy.

氮雜環及雜芳基之實例包括但不限於吡咯、咪唑、吡唑、吡啶、吡【口+井】、嘧啶、嗒【口+井】、吲【口+巾】、異吲哚、吲哚、吲唑、嘌呤、喹【口+巾】、異喹啉、喹啉、酞【口+井】、萘基吡啶、喹【口+咢】啉、喹唑啉、【口+辛】啉、喋啶、咔唑、咔啉、啡啶、吖啶、啡啉、異噻唑、啡【口+井】、異【口+咢】唑、啡【口+咢】【口+井】、啡噻【口+井】、咪唑啶、咪唑啉、哌啶、哌【口+井】、吲哚啉、嗎啉基、哌啶基、四氫呋喃基等及含雜環之N-烷氧基-氮。 Examples of nitrogen heterocycles and heteroaryl groups include, but are not limited to, pyrrole, imidazole, pyrazole, pyridine, pyridyl], pyrimidine, pyrene, sputum, sputum, sputum, sputum, sputum, sputum Anthraquinone, carbazole, anthracene, quinone [mouth + towel], isoquinoline, quinoline, hydrazine [mouth + well], naphthylpyridine, quinol [mouth + hydrazine] porphyrin, quinazoline, [mouth + octane] porphyrin , acridine, oxazole, porphyrin, phenanthridine, acridine, morphine, isothiazole, brown [mouth + well], different [mouth + 咢] azole, brown [mouth + 咢] [mouth + well], brown Thio [mouth + well], imidazolium, imidazoline, piperidine, piperazine [mouth + well], porphyrin, morpholinyl, piperidinyl, tetrahydrofuranyl, etc. and heterocyclic N-alkoxy-nitrogen .

術語「水合物」表示溶劑分子為水的複合物。 The term "hydrate" means a complex in which the solvent molecule is water.

術語「個體」、「主體」、「受試者」及「病患」係可交替使用，且代表一哺乳動物，包括但不限於靈長動物，包括猿猴及人類。 The terms "individual", "subject", "subject" and "patient" are used interchangeably and represent a mammal, including but not limited to primates, including marmosets and humans.

術語「代謝物」表示自母藥或其前藥於活體內或活體外所製造之任何式(I)化合物。 The term "metabolite" means any compound of formula (I) which is produced in vivo or ex vivo from a parent drug or a prodrug thereof.

本文所述之化合物的醫藥可接受性鹽類可由母化合物透過傳統化學方法合成而得，其中母化合物含有一鹼性或酸性部分。一般而言，可將此等化合物的自由酸或鹼形態，與化學計量的適當鹼或酸在水或有機溶劑或二者之混合物中進行反應而製備此種鹽；一般而言，較佳者為非水性媒介，例如醚、乙酸乙酯、乙醇、異丙醇或乙腈。許多適合鹽類的列表可見於Remington：The Science and Practice of Pharmacy,21st edition,Lippincott,Williams & Wilkins,(2005)。 The pharmaceutically acceptable salts of the compounds described herein can be synthesized from the parent compound by conventional chemical methods wherein the parent compound contains an alkaline or acidic moiety. In general, such salts can be prepared by reacting the free acid or base forms of such compounds with a stoichiometric amount of a suitable base or acid in water or an organic solvent or a mixture of the two; in general, preferred It is a non-aqueous medium such as ether, ethyl acetate, ethanol, isopropanol or acetonitrile. A list of many suitable salts can be found in Remington: The Science and Practice of Pharmacy, 21 st edition, Lippincott, Williams & Wilkins, (2005).

醫藥可接受性前藥表示一化合物在主體內經例如水解或氧化等代謝後形成式(I)化合物者。前藥的典型實例包括在活性化合物之官能性部分具有生物不安定性保護基團的化合物。前藥包括可被氧化、還原、胺化、去胺化、羥基化、去羥基化、水解、脫水、烷基化、去烷基化、醯基化、去醯基化、磷酸化、去磷酸化以產生活性化合物之化合物。 A pharmaceutically acceptable prodrug means a compound which is metabolized in a host, for example by hydrolysis or oxidation, to form a compound of formula (I). Typical examples of prodrugs include compounds having a biolabile protecting group in the functional portion of the active compound. Prodrugs include oxidation, reduction, amination, deamination, hydroxylation, dehydroxylation, hydrolysis, dehydration, alkylation, dealkylation, thiolation, dethiolation, phosphorylation, dephosphorylation A compound that produces an active compound.

前藥可使用本領域已知之方法由式(I)化合物輕易製備。舉例而言，請參見以下文獻：Notari,R.E.,“Theory and Practice of Prodrug Kinetics,”Methods in Enzymology,112：309 323(1985)；Bodor,N.,“Novel Approaches in Prodrug Design,”Drugs of the Future,6(3)：165 182(1981)；and Bundgaard,H.,“Design of Prodrugs：Bioreversible-Derivatives for Various Functional Groups and Chemical Entities,”in Design of Prodrugs(H.Bundgaard,ed.),Elsevier,N.Y.(1985)；Burger’s Medicinal Chemistry and Drug Chemistry,Fifth Ed.,Vol.1,pp.172 178,949 982(1995)。 Prodrugs can be readily prepared from compounds of formula (I) using methods known in the art. For example, see the following literature: Notari, RE, "Theory and Practice of Prodrug Kinetics," Methods in Enzymology , 112:309 323 (1985); Bodor, N., "Novel Approaches in Prodrug Design," Drugs of the Future , 6(3): 165 182 (1981); and Bundgaard, H., "Design of Prodrugs: Bioreversible-Derivatives for Various Functional Groups and Chemical Entities," in Design of Prodrugs (H. Bundgaard, ed.), Elsevier , NY (1985); Burger's Medicinal Chemistry and Drug Chemistry, Fifth Ed., Vol. 1, pp. 172 178, 949 982 (1995).

術語「溶劑化物」表示由一溶質(於本發明中為式(I)化合物或其鹽類或生理上具有功能性的衍生物)及一溶劑所形成的各種化學計量之複合物。就本發明之目的而言，該溶劑並不會影響該溶質的生物活性。適當溶劑的非限制性實例包括但不限於水、甲醇、乙醇及乙酸。該溶劑較佳為醫藥可接受性溶劑。醫藥可接受性溶劑的非限制性實例包括水、乙醇及乙酸。 The term "solvate" means a complex of various stoichiometry formed from a solute (in the present invention, a compound of formula (I) or a salt thereof or a physiologically functional derivative) and a solvent. For the purposes of the present invention, the solvent does not affect the biological activity of the solute. Non-limiting examples of suitable solvents include, but are not limited to, water, methanol, ethanol, and acetic acid. The solvent is preferably a pharmaceutically acceptable solvent. Non-limiting examples of pharmaceutically acceptable solvents include water, ethanol, and acetic acid.

術語「室溫」表示約20℃至約30℃範圍內的溫度。 The term "room temperature" means a temperature in the range of from about 20 ° C to about 30 ° C.

術語「經取代」欲指在所指定之原子上之一或多個氫以選自所指定之基團置換，前提為所指定之原子並未超過正常價數，且該取代產生一安定化合物。適當的所指定之基團包括，例如烷基、烯基、亞烷基、亞烯基、烷氧基、鹵基、鹵烷基、羥基、羥基烷基、芳基、雜芳基、雜環、環烷基、烷醯基、醯氧基、烷氧基羰基、胺基、亞胺基、烷基胺基、醯基胺基、硝基、三氟甲基、三氟甲氧基、羧基、羧基烷基、酮基、硫酮基、烷硫基、烷基亞磺醯基、烷基磺醯基、氰基、乙醯胺基、乙醯氧基、乙醯基、苯甲醯胺基、苯亞磺醯基、苯磺醯胺基、苯磺醯基、苯磺醯基胺基、苯甲醯基、苯甲醯基胺基、苯甲醯氧基、苯甲基、苯甲氧基、苯甲氧基羰基、苯甲基硫基、胺甲醯基、胺甲酸基、異氰酸基、胺磺醯基、胺亞磺醯基、亞磺酸基、 磺酸基、磺酸胺基、硫代磺酸基、NRxRy及/或COORx，其中各Rx及Ry獨立為H、烷基、烯基、芳基、雜芳基、雜環、環烷基或羥基。當取代基為酮基(即=O)或硫酮基(即=S)時，則原子上之兩個氫被置換。 The term "substituted" is intended to mean that one or more hydrogens on the designated atom are replaced with a group selected from the group specified, provided that the specified atom does not exceed the normal valence and that the substitution results in a stable compound. Suitable designated groups include, for example, alkyl, alkenyl, alkylene, alkenylene, alkoxy, halo, haloalkyl, hydroxy, hydroxyalkyl, aryl, heteroaryl, heterocycle , cycloalkyl, alkyl fluorenyl, decyloxy, alkoxycarbonyl, amine, imine, alkylamino, decylamino, nitro, trifluoromethyl, trifluoromethoxy, carboxyl , carboxyalkyl, keto, thioketo, alkylthio, alkylsulfinyl, alkylsulfonyl, cyano, acetylamino, ethoxylated, ethyl, benzamide Base, phenylsulfinyl, benzenesulfonylamino, benzenesulfonyl, benzenesulfonylamino, benzhydryl, benzhydrylamino, benzhydryloxy, benzyl, benzo Oxyl, benzyloxycarbonyl, benzylthio, aminemethionyl, urethane, isocyanate, amidoxime, amine sulfinyl, sulfinate, sulfonate, sulfonate An acid amine group, a thiosulfonic acid group, NR x R y and/or COOR x , wherein each R x and R y is independently H, alkyl, alkenyl, aryl, heteroaryl, heterocyclic, cycloalkyl Or hydroxyl. When the substituent is a keto group (i.e., =0) or a thioketo group (i.e., =S), then two hydrogens on the atom are replaced.

術語「治療」表示獲得理想的藥理學及/或生理學上功效。就完全或部分預防一疾病或其症狀而言，該功效可為預防性功效，且/或就部分或完全治癒一疾病及/或可歸因於該疾病的不良影響而言，該功效可為治療性功效。 The term "treatment" means obtaining the desired pharmacological and/or physiological efficacy. The efficacy may be a prophylactic effect in terms of completely or partially preventing a disease or a symptom thereof, and/or in terms of partially or completely curing a disease and/or attributable to the adverse effects of the disease, the efficacy may be Therapeutic effect.

本發明係關於多官能性喹啉衍生物，其具有以下特性：金屬螯合、清除活性含氧物、抗凝血、軸突生長及神經元增生。其可用於治療與氧化壓力及其他跟異常摺疊蛋白質凝集相關之失調所引發的神經元毒性及異常有關係的神經退化性疾病。於動物模式中，經發現腹腔注射每日1至100mg/kg(較佳為1至10mg/kg)之喹啉衍生物(B3或C12)可改善小鼠記憶而不會造成嚴重毒性。 The present invention relates to polyfunctional quinoline derivatives having the following characteristics: metal chelation, scavenging of active oxygenates, anticoagulation, axonal growth, and neuronal proliferation. It can be used to treat neurodegenerative diseases associated with oxidative stress and other neurotoxicity and abnormalities caused by disorders associated with abnormally folded protein agglutination. In the animal model, it has been found that intraperitoneal injection of a quinoline derivative (B3 or C12) of 1 to 100 mg/kg (preferably 1 to 10 mg/kg) per day improves memory in mice without causing serious toxicity.

於一方面，本發明係關於一種式(I)化合物或其醫藥可接受性鹽類、溶劑化物或水合物、前藥或代謝物： 其中R1為氫、(C1-C8)烷基、(C1-C8)伸烷基(C3-C8)環烷基、(C1-C8)鹵烷基或(C1-C8)伸烷基(C6-C20)芳基；R2為氫或鹵素；R3為氫、鹵素、(C1-C8)烷基或(C1-C8)烷氧基；R4為氫、鹵素、(C1-C8)烷基、(C1-C8)烷氧基或(C1-C8)鹵烷基；R5為氫或(C1-C20)烷醇；R6為氫；且R7為氫、(C1-C20)烷醇、(C1-C8)伸烷基(C3-C8)雜環基(C1-C20)烷醇、(C1-C8)伸烷基(C3-C8)雜環基(C1-C20)烷基、(C1-C8)伸烷基(C1-C6)烷基胺基(C1-C6)炔基、(C1-C8)伸烷基胺基(C1-C20)烷醇或(C1-C8)伸烷基胺基(C1-C20)烷醇(C1-C8)伸烷基取代之(C3-C20)雜芳基。 In one aspect, the invention relates to a compound of formula (I) or a pharmaceutically acceptable salt, solvate or hydrate, prodrug or metabolite thereof: Wherein R 1 is hydrogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkyl (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )haloalkyl or (C) 1 -C 8 )alkyl (C 6 -C 20 ) aryl; R 2 is hydrogen or halogen; R 3 is hydrogen, halogen, (C 1 -C 8 )alkyl or (C 1 -C 8 ) alkane Alkyl; R 4 is hydrogen, halogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy or (C 1 -C 8 )haloalkyl; R 5 is hydrogen or (C 1 -C 20 ) an alkanol; R 6 is hydrogen; and R 7 is hydrogen, (C 1 -C 20 ) alkanol, (C 1 -C 8 )alkyl (C 3 -C 8 )heterocyclyl (C 1 - C 20 ) alkanol, (C 1 -C 8 )alkyl (C 3 -C 8 )heterocyclyl (C 1 -C 20 )alkyl, (C 1 -C 8 )alkyl (C 1 -C 6 )alkylamino (C 1 -C 6 )alkynyl, (C 1 -C 8 )alkylamino(C 1 -C 20 )alkanol or (C 1 -C 8 )alkylene Alkylamino(C 1 -C 20 )alkanol (C 1 -C 8 )alkyl-substituted (C 3 -C 20 )heteroaryl.

於本發明一具體實施例中，其中R1為氫、CH3、CH2CH3、CH(CH3)2、CH2CH(CH3)2、CF3或苯甲基；R2為氫、F或Cl；R3為氫、F、Cl、CH3或OCH3；R4為氫、F、Cl、Br、CH3、OCH3或CF3；R5為氫、(CH2)11OH或(CH2)12OH；R6為氫；且R7為氫、(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH、(CH2)14OH、(CH2)15OH、CH2(N(CH2CH2)2N)CH2CH2OH 、CH2(N(CH2CH2)2N)CH2CH3、CH2N(CH3)CH2C≡CH、CH2NH(CH2)8OH或CH2N((CH2)6OH)CH2(8-甲氧基喹啉-2-基)。 In a particular embodiment of the invention, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , CF 3 or benzyl; R 2 is hydrogen , F or Cl; R 3 is hydrogen, F, Cl, CH 3 or OCH 3 ; R 4 is hydrogen, F, Cl, Br, CH 3 , OCH 3 or CF 3 ; R 5 is hydrogen, (CH 2 ) 11 OH or (CH 2 ) 12 OH; R 6 is hydrogen; and R 7 is hydrogen, (CH 2 ) 9 OH, (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH, (CH 2 ) 14 OH, (CH 2 ) 15 OH, CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 2 OH , CH 2 (N(CH 2 CH 2 ) 2 N CH 2 CH 3 , CH 2 N(CH 3 )CH 2 C≡CH, CH 2 NH(CH 2 ) 8 OH or CH 2 N((CH 2 ) 6 OH)CH 2 (8-methoxyquinoline) -2-base).

於本發明另一具體實施例中，其中R1為氫、CH3、CH2CH3、CH(CH3)2、CH2CH(CH3)2、CH2CH(CH2)2、CF3或苯甲基；R2、R3、R4、R5及R6係各自獨立為氫；且R7為(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH、(CH2)14OH、(CH2)15OH、CH2(N(CH2CH2)2N)CH2CH2OH或CH2N(CH3)CH2C≡CH。 In another embodiment of the invention, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 , CF 3 or benzyl; R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; and R 7 is (CH 2 ) 9 OH, (CH 2 ) 10 OH, (CH 2 ) 11 OH , (CH 2 ) 12 OH, (CH 2 ) 13 OH, (CH 2 ) 14 OH, (CH 2 ) 15 OH, CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 2 OH or CH 2 N(CH 3 )CH 2 C≡CH.

於本發明另一具體實施例中，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2或CH(CH3)2；R2、R3、R5及R6係各自獨立為氫；R4為CH3、F、Cl、Br、CF3或OCH3；且R7為(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH、(CH2)15OH、(CH2)10OCOCH3、(CH2)11OCOCH3、(CH2)12OCOCH3、(CH2)13OCOCH3、CH2NH(CH2)8OH、CH2(N(CH2CH2)2N)CH2CH2OH、CH2(N(CH2CH2)2N)CH2CH3或CH2N(CH3)CH2C≡CH。 In another embodiment of the invention, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 or CH(CH 3 ) 2 ; 2 , R 3 , R 5 and R 6 are each independently hydrogen; R 4 is CH 3 , F, Cl, Br, CF 3 or OCH 3 ; and R 7 is (CH 2 ) 9 OH, (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH, (CH 2 ) 15 OH, (CH 2 ) 10 OCOCH 3 , (CH 2 ) 11 OCOCH 3 , (CH 2 ) 12 OCOCH 3 , (CH 2 ) 13 OCOCH 3 , CH 2 NH(CH 2 ) 8 OH, CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 2 OH, CH 2 (N(CH 2 CH 2 2 N)CH 2 CH 3 or CH 2 N(CH 3 )CH 2 C≡CH.

於本發明另一具體實施例中，其中R1為氫、CH3、CH2CH3、CH(CH2)2或CH2CH(CH2)2；R2、R4係各自獨立為Cl；R3、R5及R6係各自獨立為氫；且 R7為(CH2)11OH、CH2NH(CH2)8OH或CH2N(CH3)CH2C≡CH。 In another embodiment of the invention, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH(CH 2 ) 2 or CH 2 CH(CH 2 ) 2 ; R 2 and R 4 are each independently Cl ; R 3 , R 5 and R 6 are each independently hydrogen; and R 7 is (CH 2 ) 11 OH, CH 2 NH(CH 2 ) 8 OH or CH 2 N(CH 3 )CH 2 C≡CH.

於本發明另一具體實施例中，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2、CH(CH3)2或苯甲基；R2、R3、R4、R6及R7係各自獨立為氫；且R5為(CH2)11OH或(CH2)12OH。 In another embodiment of the invention, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 , CH(CH 3 ) 2 or benzene Methyl; R 2 , R 3 , R 4 , R 6 and R 7 are each independently hydrogen; and R 5 is (CH 2 ) 11 OH or (CH 2 ) 12 OH.

於本發明另一具體實施例中，其中R1為CH3；R2、R5及R6係各自獨立為氫；R3及R4係各自獨立為OCH3或Cl；且R7為(CH2)11OH。 In another embodiment of the invention, wherein R 1 is CH 3 ; R 2 , R 5 and R 6 are each independently hydrogen; R 3 and R 4 are each independently OCH 3 or Cl; and R 7 is ( CH 2 ) 11 OH.

於本發明另一具體實施例中，該化合物係選自下列所組成之群組：9-(8-(苯甲氧基)喹啉-2-基)壬-1-醇、10-(8-(苯甲氧基)喹啉-2-基)癸-1-醇、11-(8-(苯甲氧基)喹啉-2-基)十一-1-醇、12-(8-(苯甲氧基)喹啉-2-基)十二-1-醇、13-(8-(苯甲氧基)喹啉-2-基)十三-1-醇、14-((8-(苯甲氧基)喹啉-2-基)十四-1-醇、15-(8-(苯甲氧基)喹啉-2-基)十五-1-醇、11-(8-(苯甲氧基)-5-甲基喹啉-2-基)十一-1-醇、11-(8-(苯甲氧基)-6-甲基喹啉-2-基)十一-1-醇、11-(8-(苯甲氧基)-5-氟喹啉-2-基)十一-1-醇、11-(8-(苯甲氧基)-5-氯喹啉-2-基)十一-1-醇、2-(9-羥壬基)喹啉-8-醇、2-(10-羥癸基)喹啉-8-醇、2-(11-羥十一基)喹啉-8-醇、2-(12-羥十二基)喹啉-8-醇、2-(13-羥十三基)喹啉-8-醇、2-(14-羥十四基)喹啉-8-醇、2-(15-羥十五基)喹啉-8-醇、2-(11-羥十一基)-5-甲基喹啉-8- 醇、2-(11-羥十一基)-6-甲基喹啉-8-醇、5-氯-2-(11-羥十一基)喹啉-8-醇、9-(8-甲氧基喹啉-2-基)壬-1-醇、10-(8-甲氧基喹啉-2-基)癸-1-醇、11-(8-甲氧基喹啉-2-基)十一-1-醇、12-(8-甲氧基喹啉-2-基)十二-1-醇、13-(8-甲氧基喹啉-2-基)十三-1-醇、14-((8-甲氧基喹啉-2-基)十四-1-醇、15-(8-甲氧基喹啉-2-基)十五-1-醇、11-(8-甲氧基-5-甲基喹啉-2-基)十一-1-醇、11-(5-氟-8-甲氧基喹啉-2-基)十一-1-醇、12-(5-氟-8-甲氧基喹啉-2-基)十二-1-醇、9-(5-氯-8-甲氧基喹啉-2-基)壬-1-醇、11-(5-氯-8-甲氧基喹啉-2-基)十一-1-醇、15-(5-氯-8-甲氧基喹啉-2-基)十五-1-醇、11-(5-溴-8-甲氧基喹啉-2-基)十一-1-醇、11-(8-甲氧基-5-(三氟甲基)喹啉-2-基)十一-1-醇、11-(5,8-二甲氧基喹啉-2-基)十一-1-醇、11-(8-甲氧基-6-甲基喹啉-2-基)十一-1-醇、11-(6-氟-8-甲氧基喹啉-2-基)十一-1-醇、11-(6-氯-8-甲氧基喹啉-2-基)十一-1-醇、11-(7-氟-8-甲氧基喹啉-2-基)十一-1-醇、11-(7-氯-8-甲氧基喹啉-2-基)十一-1-醇、11-(5-氯-6,8-二甲氧基喹啉-2-基)十一-1-醇、11-(6-氯-5,8-二甲氧基喹啉-2-基)十一-1-醇、11-(5,7-二氯-8-甲氧基喹啉-2-基)十一-1-醇、9-(8-乙氧基喹啉-2-基)壬-1-醇、10-(8-乙氧基喹啉-2-基)癸-1-醇、11-(8-乙氧基喹啉-2-基)十一-1-醇、12-(8-乙氧基喹啉-2-基)十二-1-醇、13-(8-乙氧基喹啉-2-基)十三-1-醇、14-((8-乙氧基喹啉-2-基)十四-1-醇、15-(8-乙氧基喹啉-2-基)十五-1-醇、11-(8-乙氧基-5-甲基喹啉-2-基)十一-1-醇、11-(8-乙氧基-5-氟喹啉-2-基)十一-1-醇、9-(5-氯-8-乙氧基喹啉-2-基)壬-1-醇、11-(5-氯-8-乙氧基喹啉-2-基)十一-1-醇、15-(5-氯-8-乙氧基喹啉-2-基)十五-1-醇、11-(5-溴-8-乙氧基喹啉-2-基)十一-1-醇、11-(5,7-二氯-8-乙氧基喹啉-2-基)十一-1-醇、9-(8-異丙氧基喹啉-2-基)壬-1-醇、10-(8-異丙氧基喹啉-2-基)癸-1-醇、11-(8-異丙氧基喹啉-2-基)十一-1-醇、 12-(8-異丙氧基喹啉-2-基)十二-1-醇、13-(8-異丙氧基喹啉-2-基)十三-1-醇、14-((8-異丙氧基喹啉-2-基)十四-1-醇、15-(8-異丙氧基喹啉-2-基)十五-1-醇、11-(8-異丙氧基-5-甲基喹啉-2-基)十一-1-醇、11-(5-氟-8-異丙氧基喹啉-2-基)十一-1-醇、9-(5-氯-8-異丙氧基喹啉-2-基)壬-1-醇、11-(5-氯-8-異丙氧基喹啉-2-基)十一-1-醇、15-(5-氯-8-異丙氧基喹啉-2-基)十五-1-醇、11-(5-溴-8-異丙氧基喹啉-2-基)十一-1-醇、15-(5-氯-8-異丙氧基喹啉-2-基)十五-1-醇、11-(5-溴-8-異丙氧基喹啉-2-基)十一-1-醇、11-(5,7-二氯-8-異丙氧基喹啉-2-基)十一-1-醇、9-(8-(環丙基甲氧基)喹啉-2-基)壬-1-醇、10-(8-(環丙基甲氧基)喹啉-2-基)癸-1-醇、11-(8-(環丙基甲氧基)喹啉-2-基)十一-1-醇、12-(8-(環丙基甲氧基)喹啉-2-基)十二-1-醇、13-(8-(環丙基甲氧基)喹啉-2-基)十三-1-醇、14-((8-(環丙基甲氧基)喹啉-2-基)十四-1-醇、15-(8-(環丙基甲氧基)喹啉-2-基)十五-1-醇、11-(8-(環丙基甲氧基)-5-甲基喹啉-2-基)十一-1-醇、11-(8-(環丙基甲氧基)-5-氟喹啉-2-基)十一-1-醇、9-(5-氯-8-(環丙基甲氧基)喹啉-2-基)壬-1-醇、11-(5-氯-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇、15-(5-氯-8-(環丙基甲氧基)喹啉-2-基)十五-1-醇、11-(5-溴-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇、11-(5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇、5,7-二氯-2-(11-羥十一基)喹啉-8-醇、10-(5-氯-8-甲氧基喹啉-2-基)癸-1-醇、乙酸10-(5-氯-8-甲氧基喹啉-2-基)癸酯、11-(5-氯-8-甲氧基喹啉-2-基)十一-1-醇、乙酸11-(5-氯-8-甲氧基喹啉-2-基)十一酯、12-(5-氯-8-甲氧基喹啉-2-基)十二-1-醇、乙酸12-(5-氯-8-甲氧基喹啉-2-基)十二酯、13-(5-氯-8-甲氧基喹啉-2-基)十三-1-醇、乙酸13-(5-氯-8-甲氧基喹啉-2-基)十三酯、11-(8-甲氧基喹啉-4-(-基)十一-1-醇、11-(8-乙氧基喹啉-4-(-基)十一-1-醇、11-(8-異丙氧基喹啉-4-(-基) 十一-1-醇、11-(8-(環丙基甲氧基)喹啉-4-(-基)十一-1-醇、11-(8-(苯甲氧基)喹啉-4-(-基)十一-1-醇、12-(8-(苯甲氧基)喹啉-4-(-基)十二-1-醇、4-((11-羥十一基)喹啉-8-醇、4-((12-羥十二基)喹啉-8-醇、9-(8-(三氟甲氧基)喹啉-2-基)壬-1-醇、11-(8-(三氟甲氧基)喹啉-2-基)十一-1-醇、14-((8-(三氟甲氧基)喹啉-2-基)十四-1-醇、15-(8-(三氟甲氧基)喹啉-2-基)十五-1-醇、2-((4-((2-羥乙基)哌【口+井】-1-基)甲基)喹啉-8-醇、2-(4-(((5-氯-8-甲氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-(4-(((5-氯-8-乙氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-(4-(((5-氯-8-異丙氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-(4-(((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基)哌【口+井】-1-基)乙烷、2-(4-(((5,7-二氯-8-甲氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-(4-(((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-((甲基(丙-2-炔基)胺基)甲基)喹啉-8-醇、5-氯-2-((甲基(丙-2-炔基)胺基)甲基)喹啉-8-醇、N((5-氯-8-甲氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5-氯-8-乙氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5-氯-8-異丙氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5,7-二氯-8-甲氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、8-((5-氯-8-甲氧基喹啉-2-基)甲基胺基)辛-1-醇、8-((5-氯-8-乙氧基喹啉-2-基)甲基胺基)辛-1-醇、8-((5-氯-8-異丙氧基喹啉-2-基)甲基胺基)辛-1-醇、8-((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基胺基)辛-1-醇、8-((5,7-二氯-8-甲氧基喹啉-2-基)甲基胺基)辛-1-醇、8-((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基胺基)辛-1-醇以及6-(雙((8-甲氧基喹啉-2-基)甲基)胺基)己-1-醇。 In another embodiment of the invention, the compound is selected from the group consisting of 9-(8-(benzyloxy)quinolin-2-yl)indol-1-ol, 10-(8) -(benzyloxy)quinolin-2-yl)indol-1-ol, 11-(8-(benzyloxy)quinolin-2-yl)undec-1-ol, 12-(8- (Benzyloxy)quinolin-2-yl)dodec-1-ol, 13-(8-(benzyloxy)quinolin-2-yl)tridec-1-ol, 14-(8 -(benzyloxy)quinolin-2-yl)tetradec-1-ol, 15-(8-(benzyloxy)quinolin-2-yl)pentadecan-1-ol, 11-(8 -(benzyloxy)-5-methylquinolin-2-yl)undec-1-ol, 11-(8-(benzyloxy)-6-methylquinolin-2-yl) 1--1-ol, 11-(8-(benzyloxy)-5-fluoroquinolin-2-yl)undec-1-ol, 11-(8-(benzyloxy)-5-chloroquine Benzan-2-yl)undec-1-ol, 2-(9-hydroxyindolyl)quinolin-8-ol, 2-(10-hydroxydecyl)quinolin-8-ol, 2-(11- Hydroxyundyl)quinoline-8-ol, 2-(12-hydroxydodecyl)quinolin-8-ol, 2-(13-hydroxytridecyl)quinolin-8-ol, 2-(14 -hydroxytetradecyl)quinoline-8-ol, 2-(15-hydroxypentadecyl)quinolin-8-ol, 2-(11-hydroxyundecyl)-5-methylquinoline-8- Alcohol, 2-(11-hydroxyundecyl)-6-methylquinolin-8-ol, 5-chloro-2-(11-hydroxyundecyl)quinolin-8-ol, 9-(8- Methoxyquinolin-2-yl)indol-1-ol, 10-(8-methoxyquinolin-2-yl)indol-1-ol, 11-(8-methoxyquinolin-2- Ethyl-1-decanol, 12-(8-methoxyquinolin-2-yl)dodec-1-ol, 13-(8-methoxyquinolin-2-yl)tridecene-1 - alcohol, 14-((8-methoxyquinolin-2-yl)tetradec-1-ol, 15-(8-methoxyquinolin-2-yl)pentadecan-1-ol, 11- (8-Methoxy-5-methylquinolin-2-yl)undec-1-ol, 11-(5-fluoro-8-methoxyquinolin-2-yl)undec-1-ol , 12-(5-fluoro-8-methoxyquinolin-2-yl)dodec-1-ol, 9-(5-chloro-8-methoxyquinolin-2-yl)indole-1- Alcohol, 11-(5-chloro-8-methoxyquinolin-2-yl)undec-1-ol, 15-(5-chloro-8-methoxyquinolin-2-yl) fifteen- 1-alcohol, 11-(5-bromo-8-methoxyquinolin-2-yl)undec-1-ol, 11-(8-methoxy-5-(trifluoromethyl)quinoline- 2-yl)undec-1-ol, 11-(5,8-dimethoxyquinolin-2-yl)undec-1-ol, 11-(8-methoxy-6-methylquin Benzan-2-yl)undec-1-ol, 11-(6-fluoro-8-methoxyquinolin-2-yl)undec-1-ol, 11-(6-chloro-8-methoxy Quinolin-2-yl)undec-1-ol, 11-(7-fluoro-8-A Quinolin-2-yl)undec-1-ol, 11-(7-chloro-8-methoxyquinolin-2-yl)undec-1-ol, 11-(5-chloro-6, 8-dimethoxyquinolin-2-yl)undec-1-ol, 11-(6-chloro-5,8-dimethoxyquinolin-2-yl)undec-1-ol, 11 -(5,7-dichloro-8-methoxyquinolin-2-yl)undec-1-ol, 9-(8-ethoxyquinolin-2-yl)indol-1-ol, 10 -(8-ethoxyquinolin-2-yl)indol-1-ol, 11-(8-ethoxyquinolin-2-yl)undec-1-ol, 12-(8-ethoxyl Quinoline-2-yl)dodec-1-ol, 13-(8-ethoxyquinolin-2-yl)tridec-1-ol, 14-((8-ethoxyquinolin-2- Tetrendyl-1-ol, 15-(8-ethoxyquinolin-2-yl)pentadecan-1-ol, 11-(8-ethoxy-5-methylquinolin-2-yl , undecyl alcohol, 11-(8-ethoxy-5-fluoroquinolin-2-yl)undec-1-ol, 9-(5-chloro-8-ethoxyquinolin-2 -yl)non-1-ol, 11-(5-chloro-8-ethoxyquinolin-2-yl)undec-1-ol, 15-(5-chloro-8-ethoxyquinoline- 2-yl)pentadecan-1-ol, 11-(5-bromo-8-ethoxyquinolin-2-yl)undec-1-ol, 11-(5,7-dichloro-8-ethyl Oxyquinolin-2-yl)undec-1-ol, 9-(8-isopropoxyquinolin-2-yl)indol-1-ol, 10-(8-isopropoxyquinoline- 2-yl)non-1-ol, 11-(8-isopropoxyquinolin-2- ) XI-1-ol, 12-(8-Isopropoxyquinolin-2-yl)dodec-1-ol, 13-(8-isopropoxyquinolin-2-yl)tridec-1-ol, 14-(( 8-isopropoxyquinolin-2-yl)tetradec-1-ol, 15-(8-isopropoxyquinolin-2-yl)pentadecan-1-ol, 11-(8-isopropyl Oxy-5-methylquinolin-2-yl)undec-1-ol, 11-(5-fluoro-8-isopropoxyquinolin-2-yl)undec-1-ol, 9- (5-chloro-8-isopropoxyquinolin-2-yl)indol-1-ol, 11-(5-chloro-8-isopropoxyquinolin-2-yl)undec-1-ol , 15-(5-chloro-8-isopropoxyquinolin-2-yl)pentadecan-1-ol, 11-(5-bromo-8-isopropoxyquinolin-2-yl) eleven 1-ol, 15-(5-chloro-8-isopropoxyquinolin-2-yl)pentadecan-1-ol, 11-(5-bromo-8-isopropoxyquinolin-2- Ethyl-1-decanol, 11-(5,7-dichloro-8-isopropoxyquinolin-2-yl)undec-1-ol, 9-(8-(cyclopropylmethoxy) ))quinolin-2-yl)indol-1-ol, 10-(8-(cyclopropylmethoxy)quinolin-2-yl)indol-1-ol, 11-(8-(cyclopropyl) Methoxy)quinolin-2-yl)undec-1-ol, 12-(8-(cyclopropylmethoxy)quinolin-2-yl)dodec-1-ol, 13-(8- (cyclopropylmethoxy)quinolin-2-yl)tridec-1-ol, 14-((8-(cyclopropylmethoxy)quinolin-2-yl)tetradec-1-ol, 15-(8-(cyclopropylmethoxy) Quinolin-2-yl)pentadecan-1-ol, 11-(8-(cyclopropylmethoxy)-5-methylquinolin-2-yl)undec-1-ol, 11-( 8-(cyclopropylmethoxy)-5-fluoroquinolin-2-yl)undec-1-ol, 9-(5-chloro-8-(cyclopropylmethoxy)quinolin-2-壬)-1-ol, 11-(5-chloro-8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol, 15-(5-chloro-8-(cyclo) Propylmethoxy)quinolin-2-yl)pentadecan-1-ol, 11-(5-bromo-8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol , 11-(5,7-Dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol, 5,7-dichloro-2-(11-hydroxy-11 Quinoline-8-ol, 10-(5-chloro-8-methoxyquinolin-2-yl)indol-1-ol, 10-(5-chloro-8-methoxyquinoline acetate-acetic acid- 2-yl) decyl ester, 11-(5-chloro-8-methoxyquinolin-2-yl)undec-1-ol, 11-(5-chloro-8-methoxyquinoline-2 acetate -yl)undecyl ester, 12-(5-chloro-8-methoxyquinolin-2-yl)dodec-1-ol, acetic acid 12-(5-chloro-8-methoxyquinoline-2 -yl)dodecyl ester, 13-(5-chloro-8-methoxyquinolin-2-yl)tridec-1-ol, 13-(5-chloro-8-methoxyquinoline-2 acetate -yl)tridecyl ester, 11-(8-methoxyquinolin-4-(-yl)undec-1-ol, 11-(8-ethoxyquinolin-4-(-yl) eleven -1-ol, 11-(8-isopropyl Quinolin-4-yl - (- yl) Undec-1-ol, 11-(8-(cyclopropylmethoxy)quinolin-4-(-yl)undec-1-ol, 11-(8-(benzyloxy)quinoline- 4-(-yl)undec-1-ol, 12-(8-(benzyloxy)quinolin-4-(-yl)dodec-1-ol, 4-((11-hydroxyundecyl) Quinoline-8-ol, 4-((12-hydroxydodecyl)quinolin-8-ol, 9-(8-(trifluoromethoxy)quinolin-2-yl)indol-1-ol , 11-(8-(Trifluoromethoxy)quinolin-2-yl)undec-1-ol, 14-((8-(trifluoromethoxy)quinolin-2-yl)tetradecene- 1-alcohol, 15-(8-(trifluoromethoxy)quinolin-2-yl)pentadecan-1-ol, 2-((4-((2-hydroxyethyl))pipeper] -1-yl)methyl)quinoline-8-ol, 2-(4-(((5-chloro-8-methoxyquinolin-2-yl)methyl)pipeper] -yl)ethanol, 2-(4-(((5-chloro-8-ethoxyquinolin-2-yl)methyl)piperidinium), 2-(4-yl)ethanol, 2-(4- (((5-Chloro-8-isopropoxyquinolin-2-yl)methyl)piperidinium [oral + well]-1-yl)ethanol, 2-(4-(((5-chloro-8-) (cyclopropylmethoxy)quinolin-2-yl)methyl)piper [mouth + well]-1-yl)ethane, 2-(4-((5,7-dichloro-8-) Oxyquinolin-2-yl)methyl)piper [mouth + well]-1-yl)ethanol, 2-(4-((5,7-dichloro-8-(cyclopropylmethoxy)) Quinoline-2-yl)methyl)piper [mouth + well]-1-yl) , 2-((methyl(prop-2-ynyl)amino)methyl)quinolin-8-ol, 5-chloro-2-((methyl(prop-2-ynyl)amino) A Quinoline-8-ol, N((5-chloro-8-methoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine, N (5 -Chloro-8-ethoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine, N((5-chloro-8-isopropoxyquinolin-2) -yl)methyl)-N-methylprop-2-yn-1-amine, N((5-chloro-8-(cyclopropylmethoxy)quinolin-2-yl)methyl)-N -methylprop-2-yn-1-amine, N((5,7-dichloro-8-methoxyquinolin-2-yl)methyl)-N-methylprop-2-yne-1 -amine, N((5,7-dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine, 8- ((5-Chloro-8-methoxyquinolin-2-yl)methylamino)octyl-1-ol, 8-((5-chloro-8-ethoxyquinolin-2-yl)-methyl Amino-1-octyl-1-ol, 8-((5-chloro-8-isopropoxyquinolin-2-yl)methylamino)octyl-1-ol, 8-((5-chloro-) 8-(cyclopropylmethoxy)quinolin-2-yl)methylamino)octyl-1-ol, 8-((5,7-dichloro-8-methoxyquinolin-2-yl) )methylamino)octyl-1-ol, 8-((5,7-dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)methylamino)octyl-1-ol And 6-(bis((8-methoxyquinolin-2-yl)methyl)amino)hexan-1-ol .

於另一方面，本發明係關於一種組成物，其包括上述化合物或其醫藥可接受性鹽類、溶劑化物或水合物、前藥或代謝物，以及一醫藥可接受性稀釋劑或載劑，用於治療神經退化性疾病。 In another aspect, the present invention relates to a composition comprising the above compound or a pharmaceutically acceptable salt, solvate or hydrate thereof, prodrug or metabolite thereof, and a pharmaceutically acceptable diluent or carrier, For the treatment of neurodegenerative diseases.

於本發明一具體實施例中，該神經退化性疾病係選自由以下疾病所組成之群組：阿茲海默症、肌萎縮性側索硬化症(ALS)、白內障、認知失調、缺血性腦中風、腦性麻痺、中風、出血性中風、庫賈氏症、海綿樣腦病變、狂牛症、癡呆症、憂鬱症、唐氏症、癲癇、創傷後癲癇、額顳葉癡呆症、妥瑞氏症、哈斯氏症(Hallerboden-Spatz disease)、亨丁頓氏症、路易氏體疾病、帕金森氏症、認知障礙、學習障礙、黃斑部病變、記憶障礙、多發性硬化症、多發性系統萎縮、運動神經元疾病、匹克氏症、漸進性核上麻痺、假性痴呆症、視網膜病變、老年癡呆症、精神分裂症暫時性缺氧誘發之神經退化、疼痛、創傷性腦損傷及脊髓損傷。 In a specific embodiment of the invention, the neurodegenerative disease is selected from the group consisting of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), cataract, cognitive dysfunction, ischemic Stroke, cerebral palsy, stroke, hemorrhagic stroke, CJD, spongiform encephalopathy, mad cow disease, dementia, depression, Down's syndrome, epilepsy, post-traumatic epilepsy, frontotemporal dementia, Toray Hallerboden-Spatz disease, Huntington's disease, Lewis' disease, Parkinson's disease, cognitive impairment, learning disabilities, macular degeneration, memory impairment, multiple sclerosis, multiple Systemic atrophy, motor neuron disease, Pick's disease, progressive nuclear paralysis, pseudo-dementia, retinopathy, Alzheimer's disease, neurodegeneration induced by temporary hypoxia, schizophrenia, pain, traumatic brain injury, and spinal cord damage.

化學Chemistry 實例1-製備(8-苯甲氧基喹啉-2-基)及(8-羥基喹啉-2-基)烷基醇Example 1 - Preparation of (8-benzyloxyquinolin-2-yl) and (8-hydroxyquinolin-2-yl)alkyl alcohol

試劑與條件：(a)BnBr,KOH,EtOH，回流，15h.；(b)1)LHMDS,THF,0℃,1h.；2)Br(CH2)n-1OH,rt,16-36h.；(c)H2,Pd/C,MeOH,rt,6至10h.；(d)BCl3,CH2Cl2,0℃至rt,3h。 Reagents and conditions : (a) BnBr, KOH, EtOH, reflux, 15 h.; (b) 1) LHMDS, THF, 0 ° C, 1 h.; 2) Br(CH 2 ) n-1 OH, rt, 16-36h (c) H 2 , Pd/C, MeOH, rt, 6 to 10 h.; (d) BCl 3 , CH 2 Cl 2 , 0 ° C to rt, 3 h.

方法：參見G.Serratrice等人之文獻[Tetrahedron,1996,52,4659-4672] 進行苯甲基化。於回流條件下，將溴甲苯(6.45g,37.7mmol)添加至含2-甲基喹吶啶(5.0g,31.4mmol)及KOH(1.95g,34.8mmol)之60ml EtOH攪拌溶液。於15小時後，過濾反應混合物並真空移除濾液。將殘餘物利用快速管柱層析法以Hex/EA(6：1)進行純化，並於己烷中再結晶以獲得中間體。將LHMDS(2.2至2.5當量)以含攪拌溶液(1當量)之20ml THF於0℃下處理1小時。將對應的Br(CH2)n-1OH(1.0至1.2當量)添加至反應混合物，並使溫度回到室溫(RT)再進行15至36小時。減壓移除溶劑。將棕色油狀殘餘物利用快速管柱層析法以Hex/EA(3：1至2：1)或DCM/EA(15：1至9：1)進行純化，並以己烷/EA再結晶以提供一系列化合物A。在10% Pd/C存在條件下於氫氣下，在室溫下移除化合物A系列的苯甲基6-10小時。過濾反應混合物，並將濾液利用快速管柱層析法以Hex/EA(4：1至3：1)進行純化以提供一系列化合物B。於含A11(0.65g,1.4mmol)之20ml CH2Cl2攪拌溶液中，於冰浴中添加1M BCl3(2.8ml,2.8mmol)達3小時。將反應混合物倒入冰浴中，並以50ml CH2Cl2萃取。於真空下濃縮有機層，並將殘餘物利用快速管柱層析法(EA)純化，以提供產物(0.31g,60%)。 Method : See Benzylation by G. Serratrice et al. [ Tetrahedron , 1996 , 52 , 4659-4672]. Bromo-toluene (6.45 g, 37.7 mmol) was added to a stirred solution of 2-methylquinacidine (5.0 g, 31.4 mmol) and KOH (1.95 g, 34.8 mmol) in 60 ml of EtOH under reflux. After 15 hours, the reaction mixture was filtered and the filtrate was evaporated in vacuo. The residue was purified by flash column chromatography using Hex / EA (6:1) and recrystallized from hexane to afford intermediate. LHMDS (2.2 to 2.5 equivalents) was treated with 20 ml of THF containing a stirred solution (1 eq.) at 0 ° C for 1 hour. The corresponding Br(CH 2 ) n-1 OH (1.0 to 1.2 equivalents) was added to the reaction mixture, and the temperature was returned to room temperature (RT) for another 15 to 36 hours. The solvent was removed under reduced pressure. The brown oily residue was purified by flash column chromatography using Hex/EA (3:1 to 2:1) or DCM/EA (15:1 to 9:1) and recrystallised from hexanes/EA To provide a series of compounds A. The benzyl group of the Compound A series was removed at room temperature for 6-10 hours in the presence of 10% Pd/C under hydrogen. The reaction mixture was filtered, and the filtrate was purified by flash column chromatography using Hex/EA (4:1 to 3:1) to afford a series of Compound B. Containing A11 (0.65g, 1.4mmol) of 20ml CH 2 Cl 2 solution was stirred in an ice bath was added 1M BCl 3 (2.8ml, 2.8mmol) for 3 hours. The reaction mixture was poured into an ice-bath and extracted with 50 ml CH 2 Cl 2 . The organic layer was concentrated under EtOAc (EtOAc)EtOAc

9-(8-(苯甲氧基)喹啉-2-基)壬-1-醇(A1)9-(8-(Benzyloxy)quinolin-2-yl)indol-1-ol (A1)

產率(YD)：53%.1H NMR(400MHz,d4-MeOD)δ8.15(d,J=8.4Hz,1H),7.52(d,J=6.8Hz,2H),7.31~7.41(m,5H),7.29(d,J=2.0Hz,1H),7.15(dd,J=7.6,2.0Hz,1H),5.40(s,2H),3.52(t,J=6.8Hz,2H),3.00(t,J=8.0Hz,2H),1.80(quin,J=6.8Hz,2H),1.50(t,J=7.2Hz,2H),1.28-1.42(br,11H)；MS.m/z 400.0,[M+Na]+。 Yield (YD): 53%. 1 H NMR (400MHz, d4 -MeOD) δ 8.15 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 6.8 Hz, 2H), 7.31~7.41 (m) , 5H), 7.29 (d, J = 2.0 Hz, 1H), 7.15 (dd, J = 7.6, 2.0 Hz, 1H), 5.40 (s, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.80 (quin, J = 6.8 Hz, 2H), 1.50 (t, J = 7.2 Hz, 2H), 1.28-1.42 (br, 11H); MS.m/z 400.0 , [M+Na] + .

10-(8-(苯甲氧基)喹啉-2-基)癸-1-醇(A2)10-(8-(benzyloxy)quinolin-2-yl)indol-1-ol (A2)

YD：41%.1H NMR(400MHz,d4-MeOD)δ8.14(d,J=8.4Hz,1H),7.52(d,J =7.6Hz,2H),7.32-7.42(m,5H),7.28(t,J=7.2Hz,1H),7.14(dd,J=7.6,1.2Hz,1H),5.38(s,2H),3.51(t,J=6.8Hz,2H),2.98(t,J=8.0Hz,2H),1.79(quin,J=7.2Hz,2H),1.49(t,J=6.8Hz,2H),1.29-1.40(br,13H)；MS.m/z 414.0,[M+Na]+。 YD:. 41% 1 H NMR (400MHz, d4 -MeOD) δ8.14 (d, J = 8.4Hz, 1H), 7.52 (d, J = 7.6Hz, 2H), 7.32-7.42 (m, 5H), 7.28 (t, J = 7.2 Hz, 1H), 7.14 (dd, J = 7.6, 1.2 Hz, 1H), 5.38 (s, 2H), 3.51 (t, J = 6.8 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H), 1.79 (quin, J = 7.2 Hz, 2H), 1.49 (t, J = 6.8 Hz, 2H), 1.29-1.40 (br, 13H); MS.m/z 414.0, [M+ Na] + .

11-(8-(苯甲氧基)喹啉-2-基)十一-1-醇(A3)11-(8-(Benzyloxy)quinolin-2-yl)undec-1-ol (A3)

YD：42%.1H NMR(400MHz,CDCl3)δ8.02(d,J=8.4Hz,1H),7.53(d,J=7.2Hz,2H),7.27-7.39(m,6H),7.02(d,J=7.6Hz,1H),5.46(s,2H),3.63(t,J=6.8Hz,2H),3.05(t,J=8Hz,2H),1.84(q,J=7.6Hz,3H),1.56(t,J=7.2Hz,2H),1.29-1.46(m,12H)；MS.m/z 428.3,[M+Na]+。 YD: 42%. 1 H NMR (400MHz, CDCl 3 ) δ 8.02 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.27-7.39 (m, 6H), 7.02 (d, J = 7.6 Hz, 1H), 5.46 (s, 2H), 3.63 (t, J = 6.8 Hz, 2H), 3.05 (t, J = 8 Hz, 2H), 1.84 (q, J = 7.6 Hz, 3H), 1.56 (t, J = 7.2 Hz, 2H), 1.29-1.46 (m, 12H); MS.m/z 428.3, [M+Na] + .

12-(8-(苯甲氧基)喹啉-2-基)十二-1-醇(A4)12-(8-(Benzyloxy)quinolin-2-yl)dodec-1-ol (A4)

YD：44%.1H NMR(400MHz,d4-MeOD)δ8.13(d,J=8.4Hz,1H),7.52(d,J=7.6Hz,2H),7.31-7.40(m,5H),7.26(d,J=7.6Hz,1H),7.13(dd,J=7.6,0.8Hz,1H),5.37(s,2H),3.51(t,J=6.8Hz,2H),2.98(t,J=7.6Hz,2H),1.78(quin,J=7.2Hz,2H),1.49(quin,J=7.2Hz,2H),1.25-1.41(m,17H)；MS.m/z 442.3,[M+Na]+。 YD: 44%. 1 H NMR (400MHz, d4 -MeOD) δ 8.13 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.6 Hz, 2H), 7.31-7.40 (m, 5H), 7.26 (d, J = 7.6 Hz, 1H), 7.13 (dd, J = 7.6, 0.8 Hz, 1H), 5.37 (s, 2H), 3.51 (t, J = 6.8 Hz, 2H), 2.98 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.2 Hz, 2H), 1.49 (quin, J = 7.2 Hz, 2H), 1.25-1.41 (m, 17H); MS.m/z 442.3, [M+ Na] + .

13-(8-(苯甲氧基)喹啉-2-基)十三-1-醇(A5)13-(8-(Benzyloxy)quinolin-2-yl)tridec-1-ol (A5)

YD：40%.1H NMR(400MHz,CDCl3)δ7.95(d,J=8.4Hz,1H),7.45(d,J=7.6Hz,2H),7.19-7.30(m,5H),6.93(d,J=7.6Hz,1H),5.40(s,2H),3.55(t,J=6.8Hz,2H),2.99(t,J=7.6Hz,2H),1.77(quin,J=7.6Hz,2H),1.46(t,J=6.8Hz,2H),1.19-1.38(br,19H)；MS.m/z 456.3,[M+Na]+。 YD: 40%. 1 H NMR (400MHz, CDCl 3 ) δ 7.95 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 7.6 Hz, 2H), 7.19-7.30 (m, 5H), 6.93 (d, J = 7.6 Hz, 1H), 5.40 (s, 2H), 3.55 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.77 (quin, J = 7.6 Hz) , 2H), 1.46 (t, J = 6.8 Hz, 2H), 1.19-1.38 (br, 19H); MS.m/z 456.3, [M+Na] + .

14-(8-(苯甲氧基)喹啉-2-基)十四-1-醇(A6)14-(8-(Benzyloxy)quinolin-2-yl)tetradec-1-ol (A6)

YD：51%.1H NMR(400MHz,d4-MeOD)δ8.14(d,J=8.4Hz,1H),7.52(d,J=7.2Hz,2H),7.33-7.42(m,5H),7.28(t,J=7.2Hz,1H),7.14(d,J=6.8Hz,1H),5.38(s,2H),3.52(t,J=6.4Hz,2H),2.98(t,J=8.0Hz,2H),1.50(quin,J=6.8Hz,2H),1.47(t,J=6.8Hz,2H),1.22-1.41(br,21H)；MS.m/z 447.3,[M+H]+。 YD:. 51% 1 H NMR (400MHz, d4 -MeOD) δ8.14 (d, J = 8.4Hz, 1H), 7.52 (d, J = 7.2Hz, 2H), 7.33-7.42 (m, 5H), 7.28 (t, J = 7.2 Hz, 1H), 7.14 (d, J = 6.8 Hz, 1H), 5.38 (s, 2H), 3.52 (t, J = 6.4 Hz, 2H), 2.98 (t, J = 8.0) Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.47 (t, J = 6.8 Hz, 2H), 1.22-1.41 (br, 21H); MS.m/z 447.3, [M+H] + .

15-(8-(苯甲氧基)喹啉-2-基)十五-1-醇(A7)15-(8-(Benzyloxy)quinolin-2-yl)pentadecan-1-ol (A7)

YD：42%.1H NMR(400MHz,d4-MeOD)δ8.15(d,J=8.4Hz,1H),7.53(d,J=7.2Hz,2H),7.35-7.43(m,5H),7.28-7.33(m,1H),7.15(dd,J=7.6,1.6Hz,1H),5.39(s,2H),3.52(t,J=6.8Hz,2H),2.99(t,J=8.0Hz,2H),1.79(quin,J=6.8Hz,2H),1.51(quin,J=6.8Hz,2H),1.22-1.41(br,23H)；MS.m/z 462.3,[M+H]+。 YD:. 42% 1 H NMR (400MHz, d4 -MeOD) δ8.15 (d, J = 8.4Hz, 1H), 7.53 (d, J = 7.2Hz, 2H), 7.35-7.43 (m, 5H), 7.28-7.33 (m, 1H), 7.15 (dd, J = 7.6, 1.6 Hz, 1H), 5.39 (s, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz) , 2H), 1.79 (quin, J = 6.8 Hz, 2H), 1.51 (quin, J = 6.8 Hz, 2H), 1.22-1.41 (br, 23H); MS.m/z 462.3, [M+H] + .

11-(8-(苯甲氧基)-5-甲基喹啉-2-基)十一-1-醇(A8)11-(8-(Benzyloxy)-5-methylquinolin-2-yl)undec-1-ol (A8)

YD：47%.1H NMR(400MHz,d4-MeOD)δ8.30(d,J=8.4Hz,1H),7.52(d,J=7.2Hz,2H),7.44(d,J=8.8Hz,1H),7.26-7.36(m,3H),7.17(d,J=8.0Hz,2H),7.02(d,J=8.0Hz,2H),5.36(s,2H),3.52(t,J=6.4Hz,2H),3.00(t,J=7.6Hz,2H),2.55(s,3H),1.80(quin,J=7.2Hz,2H),1.50(quin,J=6.8Hz,2H),1.28-1.41(m,15H)；MS.m/z 420.3,[M+H]+。 YD: 47%. 1 H NMR (400MHz, d4 -MeOD) δ 8.30 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H), 7.44 (d, J = 8.8 Hz, 1H), 7.26-7.36 (m, 3H), 7.17 (d, J = 8.0 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 5.36 (s, 2H), 3.52 (t, J = 6.4 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 2.55 (s, 3H), 1.80 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.28- 1.41 (m, 15H); MS.m/z 420.3, [M+H] + .

11-(8-(苯甲氧基)-6-甲基喹啉-2-基)十一-1-醇(A9)11-(8-(Benzyloxy)-6-methylquinolin-2-yl)undec-1-ol (A9)

YD：40%.1H NMR(400MHz,d4-MeOD)δ8.03(d,J=8.4Hz,1H),7.53(d,J=7.2Hz,2H),7.33-7.37(m,3H),7.26-7.30(m,1H),7.16(s,1H),7.00(d,J=1.2Hz,2H),5.36(s,2H),3.51(t,J=6.8Hz,2H),2.95(t,J=7.6Hz,2H),2.40(s,3H),1.76(q,J=7.6Hz,2H),1.56(t,J=7.2Hz,2H),1.29-1.46(m,15H)；MS.m/z 442.3,[M+Na]+。 YD: 40%. 1 H NMR (400MHz, d4 -MeOD) δ 8.03 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 7.2 Hz, 2H), 7.33 - 7.37 (m, 3H), 7.26-7.30 (m, 1H), 7.16 (s, 1H), 7.00 (d, J = 1.2 Hz, 2H), 5.36 (s, 2H), 3.51 (t, J = 6.8 Hz, 2H), 2.95 (t , J = 7.6 Hz, 2H), 2.40 (s, 3H), 1.76 (q, J = 7.6 Hz, 2H), 1.56 (t, J = 7.2 Hz, 2H), 1.29-1.46 (m, 15H); MS .m/z 442.3, [M+Na] + .

11-(8-(苯甲氧基)-5-氟喹啉-2-基)十一-1-醇(A10)11-(8-(Benzyloxy)-5-fluoroquinolin-2-yl)undec-1-ol (A10)

YD：43%.1H NMR(400MHz,CDCl3)δ8.28(d,J=8.8Hz,1H),7.51(d,J=7.2Hz,2H),7.33-7.40(m,3H),7.28(t,J=8.0Hz,1H),6.89~6.98(m,2H),5.42(s,2H),3.61(t,J=6.4Hz,2H),3.07(t,J=8Hz,2H),1.83(q,J=7.6Hz,2H),1.51-1.54(m,2H),1.21-1.45(m,15H)；MS.m/z 446.2,[M+Na]+。 YD: 43%. 1 H NMR (400MHz, CDCl 3 ) δ 8.28 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 7.2 Hz, 2H), 7.33-7.40 (m, 3H), 7.28 (t, J = 8.0 Hz, 1H), 6.89~6.98 (m, 2H), 5.42 (s, 2H), 3.61 (t, J = 6.4 Hz, 2H), 3.07 (t, J = 8 Hz, 2H), 1.83 (q, J = 7.6 Hz, 2H), 1.51-1.54 (m, 2H), 1.21-1.45 (m, 15H); MS.m/z 446.2, [M+Na] + .

11-(8-(苯甲氧基)-5-氯喹啉-2-基)十一-1-醇(A11)11-(8-(Benzyloxy)-5-chloroquinolin-2-yl)undec-1-ol (A11)

YD：43%.H NMR(400MHz,d4-MeOD)δ8.48(d,J=8.8Hz,1H),7.52-7.57(m,3H),7.46(d,J=8.4Hz,1H),7.35~7.39(m,2H),7.31(d,J=7.2Hz,1H), 7.14(d,J=8.4Hz,1H),5.40(s,2H),3.52(t,J=6.8Hz,2H),3.03(t,J=7.6Hz,2H),1.81(quin,J=7.2Hz,2H),1.49(t,J=6.8Hz,2H),1.28-1.41(m,15H)；MS.m/z 462.2,[M+Na]+。 YD: 43%. H NMR (400MHz, d4 -MeOD) δ 8.48 (d, J = 8.8 Hz, 1H), 7.52-7.57 (m, 3H), 7.46 (d, J = 8.4 Hz, 1H), 7.35 ~7.39 (m, 2H), 7.31 (d, J = 7.2 Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 5.40 (s, 2H), 3.52 (t, J = 6.8 Hz, 2H) , 3.03 (t, J = 7.6 Hz, 2H), 1.81 (quin, J = 7.2 Hz, 2H), 1.49 (t, J = 6.8 Hz, 2H), 1.28-1.41 (m, 15H); MS.m/ z 462.2, [M+Na] + .

2-(9-羥壬基)喹啉-8-醇(B1)2-(9-hydroxyindenyl)quinoline-8-ol (B1)

YD：85%.1H NMR(400MHz,d4-MeOD)δ7.86(d,J=8.4Hz,1H),7.22(t,J=7.6Hz,1H),7.03-7.13(m,3H),3.50(t,J=6.8Hz,2H),2.75(t,J=8.0Hz,2H),1.58(quin,J=6.8Hz,2H),1.44(quin,J=6.8Hz,2H),1.10-1.20(m,11H)；HRMS(ESI)：計算值[C18H25NO2-Na]+：310.1778，實際值：310.1779。 YD: 85%. 1 H NMR (400MHz, d4 -MeOD) δ 7.86 (d, J = 8.4 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.03-7.13 (m, 3H), 3.50 (t, J = 6.8 Hz, 2H), 2.75 (t, J = 8.0 Hz, 2H), 1.58 (quin, J = 6.8 Hz, 2H), 1.44 (quin, J = 6.8 Hz, 2H), 1.10- 1.20 (m, 11H); HRMS (ESI): calcd for [C 18 H 25 NO 2 -Na ] +: 310.1778, Found: 310.1779.

2-(10-羥癸基)喹啉-8-醇(B2)2-(10-hydroxydecyl)quinolin-8-ol (B2)

YD：85%.1H NMR(400MHz,CDCl3)δ8.01(d,J=8.4Hz,1H),7.35(t,J=6.8Hz,1H),7.26-7.28(m,2H),7.11(d,J=7.2Hz,1H),3.60(t,J=6.4Hz,2H),2.92(t,J=7.6Hz,2H),1.79(quin,J=6.8Hz,2H),1.53(quin,J=6.8Hz,2H),1.27-1.33(br,14H)；MS.m/z 302.2,[M+H]+。 YD: 85%. 1 H NMR (400MHz, CDCl 3 ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.26-7.28 (m, 2H), 7.11 (d, J = 7.2 Hz, 1H), 3.60 (t, J = 6.4 Hz, 2H), 2.92 (t, J = 7.6 Hz, 2H), 1.79 (quin, J = 6.8 Hz, 2H), 1.53 (quin) , J = 6.8 Hz, 2H), 1.27-1.33 (br, 14H); MS.m/z 302.2, [M+H] + .

2-(11-羥十一基)喹啉-8-醇(B3)2-(11-hydroxyundecyl)quinolin-8-ol (B3)

YD：77%.1H NMR(400MHz,CDCl3)δ8.04(d,J=8.4Hz,1H),7.38(t,J=7.8Hz,1H),7.27-7.31(m,2H),7.14(dd,J=1.2,7.6Hz,1H),3.64(t,J=6.8Hz,2H),2.95(t,J=7.8Hz,2H),1.83(quin,J=7.8Hz,2H),1.55(m,2H),1.28-1.36(br,17H)；1 MS.m/z 316.2,[M+H]+。 YD: 77%. 1 H NMR (400MHz, CDCl 3 ) δ 8.04 (d, J = 8.4 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.27-7.31 (m, 2H), 7.14 (dd, J = 1.2, 7.6 Hz, 1H), 3.64 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 7.8 Hz, 2H), 1.83 (quin, J = 7.8 Hz, 2H), 1.55 (m, 2H), 1.28-1.36 (br, 17H); 1 MS.m/z 316.2, [M+H] + .

2-(12-羥十二基)喹啉-8-醇(B4)2-(12-hydroxydodecyl)quinolin-8-ol (B4)

YD：76%.1H NMR(400MHz,CDCl3)δ8.03(d,J=8.4Hz,1H),7.36(t,J=8Hz,1H),7.25-7.30(m,2H),7.13(d,J=7.6Hz,1H),3.62(t,J=6.4Hz,2H),2.94(t,J=7.6Hz,2H),1.81(quin,J=7.6Hz,2H),1.54(quin,J=6.8Hz,2H),1.29-1.38(br,18H)；MS.m/z 330.3,[M+H]+。 YD: 76%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (d, J = 8.4 Hz, 1H), 7.36 (t, J = 8 Hz, 1H), 7.25-7.30 (m, 2H), 7.13 ( d, J = 7.6 Hz, 1H), 3.62 (t, J = 6.4 Hz, 2H), 2.94 (t, J = 7.6 Hz, 2H), 1.81 (quin, J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.29-1.38 (br, 18H); MS.m/z 330.3, [M+H] + .

2-(13-羥十三基)喹啉-8-醇(B5)2-(13-hydroxytridecyl)quinoline-8-ol (B5)

YD：84%.1H NMR(400MHz,CDCl3)δ8.03(d,J=8.4Hz,1H),7.36(t,J=7.6Hz,1H),7.26-7.30(m,2H),7.13(d,J=7.6Hz,1H),3.62(t,J=6.8Hz,2H), 2.95(t,J=7.6Hz,2H),1.81(quin,J=7.2Hz,2H),1.54(quin,J=6.8Hz,2H),1.25-1.34(br,20H)；MS.m/z 344.3,[M+H]+。 YD: 84%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (d, J = 8.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.26-7.30 (m, 2H), 7.13 (d, J = 7.6 Hz, 1H), 3.62 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 7.6 Hz, 2H), 1.81 (quin, J = 7.2 Hz, 2H), 1.54 (quin) , J = 6.8 Hz, 2H), 1.25-1.34 (br, 20H); MS.m/z 344.3, [M+H] + .

2-(14-羥十四基)喹啉-8-醇(B6)2-(14-hydroxytetradecyl)quinolin-8-ol (B6)

YD：87%.1H NMR(400MHz,CDCl3)δ8.02(d,J=8.8Hz,1H),7.36(t,J=7.6Hz,1H),7.25-7.29(m,2H),7.12(d,J=7.2Hz,1H),3.61(t,J=6.4Hz,2H),2.94(t,J=7.6Hz,2H),1.80(quin,J=7.2Hz,2H),1.54(quin,J=6.8Hz,2H),1.24-1.34(br,24H)；MS.m/z 358.3,[M+H]+。 YD: 87%. 1 H NMR (400MHz, CDCl 3 ) δ 8.02 (d, J = 8.8 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.25-7.29 (m, 2H), 7.12 (d, J = 7.2 Hz, 1H), 3.61 (t, J = 6.4 Hz, 2H), 2.94 (t, J = 7.6 Hz, 2H), 1.80 (quin, J = 7.2 Hz, 2H), 1.54 (quin) , J = 6.8 Hz, 2H), 1.24-1.34 (br, 24H); MS.m/z 358.3, [M+H] + .

2-(15-羥十五基)喹啉-8-醇(B7)2-(15-hydroxypentadecyl)quinoline-8-ol (B7)

YD：83%.1H NMR(400MHz,CDCl3)δ8.04(d,J=8.4Hz,1H),7.35(t,J=7.6Hz,1H),7.26-7.29(m,2H),7.13(d,J=7.2Hz,1H),3.62(t,J=6.8Hz,2H),2.95(t,J=7.6Hz,2H),1.80(quin,J=7.2Hz,2H),1.54(quin,J=7.2Hz,2H),1.24-1.37(br,24H)；MS.m/z 372.3,[M+H]+。 YD: 83%. 1 H NMR (400MHz, CDCl 3 ) δ 8.04 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.26-7.29 (m, 2H), 7.13 (d, J = 7.2 Hz, 1H), 3.62 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 7.6 Hz, 2H), 1.80 (quin, J = 7.2 Hz, 2H), 1.54 (quin , J = 7.2 Hz, 2H), 1.24-1.37 (br, 24H); MS.m/z 372.3, [M+H] + .

2-(11-羥十一基)-5-甲基喹啉-8-醇(B8)2-(11-hydroxyundecyl)-5-methylquinolin-8-ol (B8)

YD：83%.1H NMR(400MHz,d4-MeOD)δ8.26(d,J=8.4Hz,1H),7.39(d,J=8.8Hz,1H),7.15(d,J=7.2Hz,1H),6.93(d,J=3.2Hz,1H),3.52(t,J=6.4Hz,2H),2.95(t,J=8.0Hz,2H),2.53(s,3H),1.81(quin,J=7.2Hz,2H),1.48(quin,J=6.8Hz,2H),1.13-1.37(m,15H)；MS.m/z 330.3,[M+H]+。 YD: 83%. 1 H NMR (400MHz, d4 -MeOD) δ 8.26 (d, J = 8.4 Hz, 1H), 7.39 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 6.93 (d, J = 3.2 Hz, 1H), 3.52 (t, J = 6.4 Hz, 2H), 2.95 (t, J = 8.0 Hz, 2H), 2.53 (s, 3H), 1.81 (quin, J = 7.2 Hz, 2H), 1.48 (quin, J = 6.8 Hz, 2H), 1.13-1.37 (m, 15H); MS.m/z 330.3, [M+H] + .

2-(11-羥十一基)-6-甲基喹啉-8-醇(B9)2-(11-hydroxyundecyl)-6-methylquinolin-8-ol (B9)

YD：83%.1H NMR(400MHz,d4-MeOD)δ7.99(d,J=8.4Hz,1H),7.29(d,J=8.8Hz,1H),7.06(s,1H),6.91(s,1H),3.51(t,J=6.4Hz,2H),2.90(t,J=8.0Hz,2H),2.41(s,3H),1.77(quin,J=6.4Hz,2H),1.49(quin,J=6.8Hz,2H),1.25-1.37(m,19H)；MS.m/z 352.2,[M+Na]+。 YD: 83%. 1 H NMR (400MHz, d4 -MeOD) δ 7.99 (d, J = 8.4 Hz, 1H), 7.29 (d, J = 8.8 Hz, 1H), 7.06 (s, 1H), 6.91 ( s, 1H), 3.51 (t, J = 6.4 Hz, 2H), 2.90 (t, J = 8.0 Hz, 2H), 2.41 (s, 3H), 1.77 (quin, J = 6.4 Hz, 2H), 1.49 ( Quin, J = 6.8 Hz, 2H), 1.25-1.37 (m, 19H); MS.m/z 352.2, [M+Na] + .

5-氯-2-(11-羥十一基)喹啉-8-醇(B10)5-chloro-2-(11-hydroxyundecyl)quinolin-8-ol (B10)

1H NMR(400MHz,d4-MeOD)δ8.39(d,J=8.8Hz,1H),7.49(d,J=8.8Hz,1H),7.41(d,J=8.4Hz,1H),7.01(d,J=8.0Hz,1H),3.51(t,J=6.4Hz,2H),2.98(t,J=8.0Hz,2H),1.81(quin,J=7.2Hz,2H),1.50(quin,J=6.8Hz,2H), 1.27-1.35(m,15H)；MS.m/z 350.2,[M+H]+。 1 H NMR (400MHz, d4 -MeOD ) δ8.39 (d, J = 8.8Hz, 1H), 7.49 (d, J = 8.8Hz, 1H), 7.41 (d, J = 8.4Hz, 1H), 7.01 ( d, J = 8.0 Hz, 1H), 3.51 (t, J = 6.4 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H), 1.81 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.27-1.35 (m, 15H); MS.m/z 350.2, [M+H] + .

實例2-製備(8-甲氧基喹啉-2-基)烷基醇Example 2 - Preparation of (8-methoxyquinolin-2-yl)alkyl alcohol

試劑與條件：(a)MeI,K2CO3，丙酮，r.t,10h.；(b)1)LHMDS,THF,0℃,1h.；2)Br(CH2)n-1OH,rt,12-30h。 Reagents and conditions : (a) MeI, K 2 CO 3 , acetone, rt, 10 h.; (b) 1) LHMDS, THF, 0 ° C, 1 h.; 2) Br(CH 2 ) n-1 OH, rt, 12-30h.

方法：於RT下將碘甲烷(10.8g,76.3mmol)添加至含2-甲基喹吶啶(1.0g,6.3mmol)及K2CO3(5.0g,36.2mmol)之30ml丙酮攪拌溶液10小時。過濾反應混合物並減壓移除濾液。將殘餘物利用快速管柱層析法以Hex/EA(3：1)進行純化，並以己烷/EA再結晶以獲得中間體8-甲氧基-2-甲基喹啉。將LHMDS(2.2至2.5當量)以含中間體(1當量)攪拌溶液之THF於0℃下處理1小時。將對應的Br(CH2)n-1OH(1.0至1.2當量)添加至反應混合物，並使溫度回到RT再進行12至30h。減壓移除溶劑。將棕色油狀殘餘物利用快速管柱層析法以Hex/EA或DCM/EA進行純化，並以Hex/EA再結晶以提供一系列化合物C。 Method : Methyl iodide (10.8 g, 76.3 mmol) was added to a stirred solution of 30 ml of acetone containing 2-methylquinacridine (1.0 g, 6.3 mmol) and K 2 CO 3 (5.0 g, 36.2 mmol) at RT. hour. The reaction mixture was filtered and the filtrate was removed under reduced pressure. The residue was purified by flash column chromatography eluting with Hex / EA (3:1) and recrystallized from hexane/EA to afford intermediate 8-methoxy-2-methylquinoline. LHMDS (2.2 to 2.5 eq.) was treated with THF containing intermediate (1 eq.). The corresponding Br(CH 2 ) n-1 OH (1.0 to 1.2 equivalents) was added to the reaction mixture, and the temperature was returned to RT for another 12 to 30 h. The solvent was removed under reduced pressure. The brown oily residue was purified by flash column chromatography using Hex / EA or DCM / EA and recrystallised from Hex / EA to afford a series of Compound C.

9-(8-甲氧基喹啉-2-基)壬-1-醇(C1)9-(8-methoxyquinolin-2-yl)indol-1-ol (C1)

YD：50%.1H NMR(400MHz,CDCl3)δ8.05(d,J=8.4Hz,1H),7.33-7.42(m,3H),7.04(d,J=6.8Hz,1H),4.08(s,3H),3.62(t,J=6.4Hz,2H),3.07(t,J=7.6Hz,2H),1.79(br,2H),1.53(br,2H),1.30-1.42(br,11H)；MS.m/z 324.0,[M+Na]+。 YD: 50%. 1 H NMR (400MHz, CDCl 3 ) δ 8.05 (d, J = 8.4 Hz, 1H), 7.33-7.42 (m, 3H), 7.04 (d, J = 6.8 Hz, 1H), 4.08 (s, 3H), 3.62 (t, J = 6.4 Hz, 2H), 3.07 (t, J = 7.6 Hz, 2H), 1.79 (br, 2H), 1.53 (br, 2H), 1.30-1.42 (br, 11H); MS.m/z 324.0, [M+Na] + .

10-(8-甲氧基喹啉-2-基)癸-1-醇(C2)10-(8-methoxyquinolin-2-yl)indol-1-ol (C2)

YD：38%.1H NMR(400MHz,CDCl3)δ 8.01(d,J=8.4Hz,1H),7.36(t,J= 7.6Hz,1H),7.30-7.33(m,2H),7.00(d,J=7.6Hz,1H),4.05(s,3H),3.60(t,J=6.8Hz,2H),3.01(t,J=7.6Hz,2H),1.79(quin,J=8Hz,2H),1.52(quin,J=6.8Hz,2H),1.30-1.43(br,12H)；MS.m/z 316.2,[M+H]+。 YD: 38%. 1 H NMR (400MHz, CDCl 3 ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.30-7.33 (m, 2H), 7.00 ( d, J = 7.6 Hz, 1H), 4.05 (s, 3H), 3.60 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 7.6 Hz, 2H), 1.79 (quin, J = 8 Hz, 2H) ), 1.52 (quin, J = 6.8 Hz, 2H), 1.30-1.43 (br, 12H); MS.m/z 316.2, [M+H] + .

11-(8-甲氧基喹啉-2-基)十一-1-醇(C3)11-(8-methoxyquinolin-2-yl)undec-1-ol (C3)

YD：42%.1H NMR(400MHz,CDCl3)δ8.02(d,J=8.8Hz,1H),7.38(t,J=7.8Hz,1H),7.31-7.34(m,2H),7.15(d,J=7.2Hz,1H),4.06(s,3H),3.61(t,J=6.8Hz,2H),3.02(t,J=7.8Hz,2H),1.79(quin,J=7.6Hz,2H),1.54(quin,J=6.8Hz,2H),1.31-1.42(br,15H)；MS.m/z 352.2,[M+Na]+。 YD: 42%. 1 H NMR (400MHz, CDCl 3 ) δ 8.02 (d, J = 8.8 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.31-7.34 (m, 2H), 7.15 (d, J = 7.2 Hz, 1H), 4.06 (s, 3H), 3.61 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 7.8 Hz, 2H), 1.79 (quin, J = 7.6 Hz) , 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.31-1.42 (br, 15H); MS.m/z 352.2, [M+Na] + .

12-(8-甲氧基喹啉-2-基)十二-1-醇(C4)12-(8-methoxyquinolin-2-yl)dodec-1-ol (C4)

YD：38%.1H NMR(400MHz,CDCl3)δ8.01(d,J=8.8Hz,1H),7.35(t,J=7.6Hz,1H),7.30-7.32(m,2H),7.01(d,J=7.2Hz,1H),4.05(s,3H),3.61(t,J=6.4Hz,2H),3.01(t,J=8Hz,2H),1.78(quin,J=7.6Hz,2H),1.36-1.41(m,2H),1.24-1.33(br,16H)；MS.m/z 344.3,[M+H]+。 YD: 38%. 1 H NMR (400MHz, CDCl 3 ) δ 8.01 (d, J = 8.8 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.30-7.32 (m, 2H), 7.01 (d, J = 7.2 Hz, 1H), 4.05 (s, 3H), 3.61 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.36-1.41 (m, 2H), 1.24-1.33 (br, 16H); MS.m/z 344.3, [M+H] + .

13-(8-甲氧基喹啉-2-基)十三-1-醇(C5)13-(8-methoxyquinolin-2-yl)tridec-1-ol (C5)

YD：38%.1H NMR(400MHz,CDCl3)δ8.01(d,J=8.4Hz,1H),7.37(t,J=7.6Hz,1H),7.30-7.33(m,2H),7.01(d,J=7.6Hz,1H),4.05(s,3H),3.61(t,J=7.2Hz,2H),3.01(t,J=8Hz,2H),1.80(quin,J=7.6Hz,2H),1.54(quin,J=6.8Hz,2H),1.36-1.43(br,19H)；MS.m/z 358.3,[M+H]+。 YD: 38%. 1 H NMR (400MHz, CDCl 3 ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.30-7.33 (m, 2H), 7.01 (d, J = 7.6 Hz, 1H), 4.05 (s, 3H), 3.61 (t, J = 7.2 Hz, 2H), 3.01 (t, J = 8 Hz, 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz, 2H), 1.36-1.43 (br, 19H); MS.m/z 358.3, [M+H] + .

14-(8-甲氧基喹啉-2-基)十四-1-醇(C6)14-(8-methoxyquinolin-2-yl)tetradec-1-ol (C6)

YD：38%.1H NMR(400MHz,CDCl3)δ8.02(d,J=8.4Hz,1H),7.31-7.38(m,3H),7.01(d,J.=7.2Hz,1H),4.06(s,3H),3.61(t,J=6.8Hz,2H),3.02(t,J=8Hz,2H),1.79(quin,J=7.6Hz,2H),1.54(quin,J=6.8Hz,2H),1.23-1.40(br,21H)；MS.m/z 394.3,[M+Na]+。 YD: 38%. 1 H NMR (400MHz, CDCl 3 ) δ 8.02 (d, J = 8.4 Hz, 1H), 7.31-7.38 (m, 3H), 7.01 (d, J. = 7.2 Hz, 1H), 4.06(s,3H), 3.61 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 8 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz) , 2H), 1.23-1.40 (br, 21H); MS.m/z 394.3, [M+Na] + .

15-(8-甲氧基喹啉-2-基)十五-1-醇(C7)15-(8-methoxyquinolin-2-yl)pentadecan-1-ol (C7)

YD：31%.1H NMR(400MHz,CDCl3)δ8.01(d,J=8.4Hz,1H),7.31-7.39(m,3H),7.01(d,J=7.2Hz,1H),4.06(s,3H),3.63(t,J=6.8Hz,2H),3.02(t,J=8 Hz,2H),1.79(quin,J=7.6Hz,2H),1.54(quin,J=6.8Hz,2H),1.32-1.43(br,23H)；MS.m/z 408.3,[M+H]+。 YD: 31%. 1 H NMR (400MHz, CDCl 3 ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.31-7.39 (m, 3H), 7.01 (d, J = 7.2 Hz, 1H), 4.06 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 8 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.54 (quin, J = 6.8 Hz) , 2H), 1.32-1.43 (br, 23H); MS.m/z 408.3, [M+H] + .

11-(8-甲氧基-5-甲基喹啉-2-基)十一-1-醇(C8)11-(8-Methoxy-5-methylquinolin-2-yl)undec-1-ol (C8)

YD：30%.1H NMR(400MHz,d4-MeOD)δ8.29(d,J=8.4Hz,1H),7.43(d,J=8.8Hz,1H),7.24(dd,J=8.0,0.8Hz,1H),7.01(d,J=8.0Hz,1H),4.00(s,3H),3.51(t,J=6.8Hz,2H),2.97(t,J=8.0Hz,2H),2.56(s,3H),1.76(quin,J=7.6Hz,2H),1.50(quin,J=7.2Hz,2H),1.27-1.40(br,15H)；MS.m/z 366.2,[M+Na]+。 YD: 30%. 1 H NMR (400MHz, d4 -MeOD) δ 8.29 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 8.8 Hz, 1H), 7.24 (dd, J = 8.0, 0.8 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 4.00 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 2.97 (t, J = 8.0 Hz, 2H), 2.56 ( s, 3H), 1.76 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 7.2 Hz, 2H), 1.27-1.40 (br, 15H); MS.m/z 366.2, [M+Na] + .

11-(5-氟-8-甲氧基喹啉-2-基)十一-1-醇(C9)11-(5-fluoro-8-methoxyquinolin-2-yl)undec-1-ol (C9)

1H NMR(400MHz,d4-MeOD)δ8.34(d,J=8.8Hz,1H),7.51(d,J=8.8Hz,1H),7.15(d,J=7.2Hz,1H),6.93(d,J=3.2Hz,1H),4.02(s,3H),3.52(t,J=6.8Hz,2H),2.95(t,J=8.0Hz,2H),1.81(quin,J=7.2Hz,2H),1.48(quin,J=6.8Hz,2H),1.13-1.37(m,15H)；MS.m/z 370.2,[M+Na]+。 1 H NMR (400MHz, d4 -MeOD ) δ8.34 (d, J = 8.8Hz, 1H), 7.51 (d, J = 8.8Hz, 1H), 7.15 (d, J = 7.2Hz, 1H), 6.93 ( d, J = 3.2 Hz, 1H), 4.02 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 8.0 Hz, 2H), 1.81 (quin, J = 7.2 Hz, 2H), 1.48 (quin, J = 6.8 Hz, 2H), 1.13-1.37 (m, 15H); MS.m/z 370.2, [M+Na] + .

12-(5-氟-8-甲氧基喹啉-2-基)十二-1-醇(C10)12-(5-fluoro-8-methoxyquinolin-2-yl)dodec-1-ol (C10)

YD：38%.1H NMR(400MHz,d4-MeOD)δ8.36(d,J=8.8Hz,1H),7.52(d,J=8.8Hz,1H),7.17(d,J=8.8Hz,1H),7.08(dd,J=8.4,4.8Hz,1H),4.04(s,3H),3.53(t,J=6.8Hz,2H),3.00(t,J=8.0Hz,2H),1.78(quin,J=7.2Hz,2H),1.51(quin,J=7.2Hz,2H),1.28-1.42(m,17H)；MS.m/z 384.2,[M+Na]+。 YD: 38%. 1 H NMR (400MHz, d4 -MeOD) δ 8.36 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.17 (d, J = 8.8 Hz, 1H), 7.08 (dd, J = 8.4, 4.8 Hz, 1H), 4.04 (s, 3H), 3.53 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.78 ( Quin, J = 7.2 Hz, 2H), 1.51 (quin, J = 7.2 Hz, 2H), 1.28-1.42 (m, 17H); MS.m/z 384.2, [M+Na] + .

9-(5-氯-8-甲氧基喹啉-2-基)壬-1-醇(C11)9-(5-chloro-8-methoxyquinolin-2-yl)indol-1-ol (C11)

YD：38%.1H NMR(400MHz,d4-MeOD)δ8.47(d,J=8.8Hz,1H),7.55(d,J=8.8Hz,1H),7.52(d,J=8.4Hz,1H),7.11(d,J=8.8Hz,1H),4.04(s,3H),3.51(t,J=6.8Hz,2H),3.00(t,J=8.0Hz,2H),1.77(quin,J=7.6Hz,2H),1.50(quin,J=6.8Hz,2H),1.30-1.37(m,11H)；MS.m/z 336.2,[M+H]+。 YD: 38%. 1 H NMR (400MHz, d4 -MeOD) δ 8.47 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.11 (d, J = 8.8 Hz, 1H), 4.04 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.30-1.37 (m, 11H); MS.m/z 336.2, [M+H] + .

11-(5-氯-8-甲氧基喹啉-2-基)十一-1-醇(C12)11-(5-chloro-8-methoxyquinolin-2-yl)undec-1-ol (C12)

YD：35%.1H NMR(400MHz,d4-MeOD)δ8.46(d,J=8.4Hz,1H),7.54(d,J=8.8Hz,1H),7.51(d,J=8.4Hz,1H),7.10(d,J=8.4Hz,1H),4.04(s,3H), 3.51(t,J=6.8Hz,2H),2.99(t,J=8.0Hz,2H),1.76(quin,J=7.6Hz,2H),1.49(quin,J=6.8Hz,2H),1.27-1.38(br,15H)；MS.m/z 386.2,[M+Na]+。 YD: 35%. 1 H NMR (400MHz, d4 -MeOD) δ 8.46 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.76 (quin, J = 7.6 Hz, 2H), 1.49 (quin, J = 6.8 Hz, 2H), 1.27-1.38 (br, 15H); MS.m/z 386.2, [M+Na] + .

15-(5-氯-8-甲氧基喹啉-2-基)十五-1-醇(C13)15-(5-chloro-8-methoxyquinolin-2-yl)pentadecan-1-ol (C13)

YD：39%.1H NMR(400MHz,d4-MeOD+CDCl3)δ8.44(d,J=8.4Hz,1H),7.47(d,J=8.4Hz,1H),7.46(d,J=8.4Hz,1H),7.01(dd,J=8.4,4.0Hz,1H),4.03(s,3H),3.52(t,J=6.8Hz,2H),2.99(t,J=8.0Hz,2H),1.76(quin,J=7.6Hz,2H),1.50(quin,J=6.8Hz,2H),1.22-1.38(m,23H)；MS.m/z 442.3,[M+Na]+。 YD: 39%. 1 H NMR (400MHz, d4 -MeOD + CDCl 3 ) δ 8.44 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.01 (dd, J = 8.4, 4.0 Hz, 1H), 4.03 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H) , 1.76 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.22-1.38 (m, 23H); MS.m/z 442.3, [M+Na] + .

11-(5-溴-8-甲氧基喹啉-2-基)十一-1-醇(C14)11-(5-Bromo-8-methoxyquinolin-2-yl)undec-1-ol (C14)

YD：46%.1H NMR(400MHz,CDCl3)δ8.40(d,J=8.4Hz,1H),7.65(d,J=8.4Hz,1H),7.44(d,J=8.8Hz,1H),6.91(d,J=8.4Hz,1H),4.06(s,3H),3.63(t,J=6.8Hz,2H),3.07(t,J=8.0Hz,2H),1.79(quin,J=7.6Hz,2H),1.55(quin,J=6.8Hz,2H),1.30-1.45(br,15H)；MS.m/z 430.2,[M+Na]+。 YD: 46%. 1 H NMR (400MHz, CDCl 3 ) δ 8.40 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H) ), 6.91 (d, J = 8.4 Hz, 1H), 4.06 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.07 (t, J = 8.0 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.55 (quin, J = 6.8 Hz, 2H), 1.30-1.45 (br, 15H); MS.m/z 430.2, [M+Na] + .

11-(8-甲氧基-5-(三氟甲基)喹啉-2-基)十一-1-醇(C15)11-(8-Methoxy-5-(trifluoromethyl)quinolin-2-yl)undec-1-ol (C15)

YD：36%.1H NMR(400MHz,d4-MeOD+CDCl3)δ8.40(dq,J=10.4,1.6Hz,1H),7.86(d,J=8.4Hz,1H),7.58(d,J=8.8Hz,1H),7.20(d,J=8.0Hz,1H),4.11(s,3H),3.51(t,J=6.8Hz,2H),3.00(t,J=8.0Hz,2H),1.78(quin,J=7.6Hz,2H),1.50(quin,J=6.8Hz,2H),1.27-1.43(m,15H)；MS.m/z 420.2,[M+Na]+。 YD: 36%. 1 H NMR (400MHz, d4 -MeOD+CDCl 3 ) δ 8.40 (dq, J = 10.4, 1.6 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 4.11 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H) , 1.78 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.27-1.43 (m, 15H); MS.m/z 420.2, [M+Na] + .

11-(5,8-二甲氧基喹啉-2-基)十一-1-醇(C16)11-(5,8-dimethoxyquinolin-2-yl)undec-1-ol (C16)

YD：31%；1H NMR(400MHz,d4-MeOD)δ8.46(d,J=8.4Hz,1H),7.38(d,J=8.4Hz,1H),7.03(d,J=8.4Hz,1H),6.82(d,J=8.4Hz,1H),3.98(s,3H),3.94(s,3H),3.51(t,J=6.8Hz,2H),2.95(t,J=8.0Hz,2H),1.73(quin,J=7.6Hz,2H),1.50(quin,J=6.8Hz,2H),1.27-1.35(br,15H)；MS.m/z 360.2,[M+H]+。 YD: 31%; 1 H NMR (400MHz, d4 -MeOD) δ 8.46 (d, J = 8.4 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.4 Hz, 1H), 6.82 (d, J = 8.4 Hz, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 8.0 Hz, 2H), 1.73 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.27-1.35 (br, 15H); MS.m/z 360.2, [M+H] + .

11-(8-甲氧基-6-甲基喹啉-2-基)十一-1-醇(C17)11-(8-methoxy-6-methylquinolin-2-yl)undec-1-ol (C17)

YD：41%.1H NMR(400MHz,CDCl3)δ7.96(d,J=8.4Hz,1H),7.30(t,J=8.4Hz,1H),7.12(s,1H),6.87(s,1H),4.06(s,3H),3.63(t,J=6.8Hz,2H),3.05(t,J=7.6Hz,2H),2.50(s,3H),1.79(quin,J=8.0Hz,2H),1.55(quin,J=6.8Hz,2H),1.27-1.41(br,15H)；MS.m/z 366.2,[M+Na]+。 YD: 41%. 1 H NMR (400MHz, CDCl 3 ) δ 7.96 (d, J = 8.4 Hz, 1H), 7.30 (t, J = 8.4 Hz, 1H), 7.12 (s, 1H), 6.87 (s) , 1H), 4.06 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.05 (t, J = 7.6 Hz, 2H), 2.50 (s, 3H), 1.79 (quin, J = 8.0 Hz) , 2H), 1.55 (quin, J = 6.8 Hz, 2H), 1.27-1.41 (br, 15H); MS.m/z 366.2, [M+Na] + .

11-(6-氟-8-甲氧基喹啉-2-基)十一-1-醇(C18)11-(6-fluoro-8-methoxyquinolin-2-yl)undec-1-ol (C18)

YD：41%；1H NMR(400MHz,d4-MeOD)δ8.12(d,J=8.4Hz,1H),7.44(d,J=8.8Hz,1H),7.07(dd,J=9.2,2.4Hz,1H),7.01(dd,J=10.8,2.8Hz,1H),4.06(s,3H),3.52(t,J=6.8Hz,2H),2.95(t,J=8.0Hz,2H),1.75(quin,J=7.6Hz,2H),1.48(quin,J=7.2Hz,2H),1.19-1.35(m,15H)；MS.m/z 348.2,[M+H]+。 YD: 41%; 1 H NMR (400MHz, d4 -MeOD) δ 8.12 (d, J = 8.4 Hz, 1H), 7.44 (d, J = 8.8 Hz, 1H), 7.07 (dd, J = 9.2, 2.4 Hz, 1H), 7.01 (dd, J = 10.8, 2.8 Hz, 1H), 4.06 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.95 (t, J = 8.0 Hz, 2H), 1.75 (quin, J = 7.6 Hz, 2H), 1.48 (quin, J = 7.2 Hz, 2H), 1.19-1.35 (m, 15H); MS.m/z 348.2, [M+H] + .

11-(6-氯-8-甲氧基喹啉-2-基)十一-1-醇(C19)11-(6-chloro-8-methoxyquinolin-2-yl)undec-1-ol (C19)

YD：39%；1H NMR(400MHz,d4-MeOD)δ8.11(d,J=8.4Hz,1H),7.44-7.47(m,2H),7.13(d,J=2.0Hz,1H),4.05(s,3H),3.52(t,J=6.8Hz,2H),2.96(t,J=8.0Hz,2H),1.76(quin,J=7.2Hz,2H),1.50(quin,J=6.8Hz,2H),1.28-1.36(br,15H)；MS.m/z 360.2,[M+H]+。 YD: 39%; 1 H NMR (400MHz, d4 -MeOD) δ8.11 (d, J = 8.4Hz, 1H), 7.44-7.47 (m, 2H), 7.13 (d, J = 2.0Hz, 1H), 4.05(s,3H), 3.52 (t, J = 6.8 Hz, 2H), 2.96 (t, J = 8.0 Hz, 2H), 1.76 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8) Hz, 2H), 1.28-1.36 (br, 15H); MS.m/z 360.2, [M+H] + .

11-(7-氟-8-甲氧基喹啉-2-基)十一-1-醇(C20)11-(7-fluoro-8-methoxyquinolin-2-yl)undec-1-ol (C20)

YD：32%；1H NMR(400MHz,d4-MeOD)δ8.20(d,J=8.8Hz,1H),7.60(dd,J=8.8,5.6Hz,1H),7.39(dd,J=8.8,1.6Hz,1H),7.01(d,J=8.8Hz,1H),4.13(d,J=1.2Hz,3H),3.52(t,J=6.8Hz,2H),2.99(t,J=7.6Hz,2H),1.80(quin,J=7.6Hz,2H),1.48(quin,J=6.8Hz,2H),1.29-1.42(m,15H)；MS.m/z 348.2,[M+H]+。 YD: 32%; 1 H NMR (400MHz, d4 -MeOD) δ 8.20 (d, J = 8.8 Hz, 1H), 7.60 (dd, J = 8.8, 5.6 Hz, 1H), 7.39 (dd, J = 8.8 , 1.6 Hz, 1H), 7.01 (d, J = 8.8 Hz, 1H), 4.13 (d, J = 1.2 Hz, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6) Hz, 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.48 (quin, J = 6.8 Hz, 2H), 1.29-1.42 (m, 15H); MS.m/z 348.2, [M+H] + .

11-(7-氯-8-甲氧基喹啉-2-基)十一-1-醇(C21)11-(7-chloro-8-methoxyquinolin-2-yl)undec-1-ol (C21)

YD：17%；1H NMR(400MHz,d4-MeOD)δ8.20(d,J=8.4Hz,1H),7.60(d,J=8.8Hz,1H),7.50(d,J=8.8Hz,1H),7.42(d,J=8.4Hz,1H),4.08(s,3H),3.52(t,J=6.8Hz,2H),2.99(t,J=7.6Hz,2H),1.82(quin,J=7.2Hz,2H),1.50(quin,J=6.8Hz,2H),1.28-1.42(br,15H)；MS.m/z 360.2,[M+H]+。 YD: 17%; 1 H NMR (400MHz, d4 -MeOD) δ 8.20 (d, J = 8.4 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 4.08 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.82 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.28-1.42 (br, 15H); MS.m/z 360.2, [M+H] + .

11-(5-氯-6,8-二甲氧基喹啉-2-基)十一-1-醇(C22)11-(5-chloro-6,8-dimethoxyquinolin-2-yl)undec-1-ol (C22)

YD：32%；1H NMR(400MHz,d4-MeOD)δ8.40(d,J=8.8Hz,1H),7.46(d,J=8.8Hz,1H),7.07(s,1H),4.08(s,3H),4.02(s,3H),3.51(t,J=6.8Hz,2H),2.94(t,J=7.6Hz,2H),1.74(quin,J=7.6Hz,2H),1.50(quin,J=6.8Hz,2H),1.27-1.34(br,15H)；MS.m/z 394.2,[M+H]+。 YD: 32%; 1 H NMR (400MHz, d4 -MeOD) δ 8.40 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H), 7.07 (s, 1H), 4.08 ( s, 3H), 4.02 (s, 3H), 3.51 (t, J = 6.8 Hz, 2H), 2.94 (t, J = 7.6 Hz, 2H), 1.74 (quin, J = 7.6 Hz, 2H), 1.50 ( Quin, J = 6.8 Hz, 2H), 1.27-1.34 (br, 15H); MS.m/z 394.2, [M+H] + .

11-(6-氯-5,8-二甲氧基喹啉-2-基)十一-1-醇(C23)11-(6-chloro-5,8-dimethoxyquinolin-2-yl)undec-1-ol (C23)

YD：35%；1H NMR(400MHz,d4-MeOD)δ8.38(d,J=8.8Hz,1H),7.51(d,J=8.4Hz,1H),7.12(s,1H),4.02(s,3H),3.94(s,3H),3.52(t,J=6.4Hz,2H),2.97(t,J=7.6Hz,2H),1.74(quin,J=7.6Hz,2H),1.50(quin,J=6.8Hz,2H),1.34-1.41(br,15H)；MS.m/z 394.2,[M+H]+。 YD: 35%; 1 H NMR (400MHz, d4 -MeOD) δ 8.38 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.12 (s, 1H), 4.02 ( s, 3H), 3.94 (s, 3H), 3.52 (t, J = 6.4 Hz, 2H), 2.97 (t, J = 7.6 Hz, 2H), 1.74 (quin, J = 7.6 Hz, 2H), 1.50 ( Quin, J = 6.8 Hz, 2H), 1.34-1.41 (br, 15H); MS.m/z 394.2, [M+H] + .

11-(5,7-二氯-8-甲氧基喹啉-2-基)十一-1-醇(C24)11-(5,7-Dichloro-8-methoxyquinolin-2-yl)undec-1-ol (C24)

YD：40%.1H NMR(400MHz,CDCl3)δ8.40(d,J=8.4Hz,1H),7.59(d,J=8.0Hz,1H),7.56(s,1H),7.39(d,J=8.8Hz,1H),4.19(s,3H),3.63(t,J=6.8Hz,2H),3.04(t,J=7.6Hz,2H),1.84(quin,J=7.2Hz,2H),1.55(quin,J=6.8Hz,2H),1.27-1.40(br,15H)；MS.m/z 420.2,[M+Na]+。 YD: 40%. 1 H NMR (400MHz, CDCl 3 ) δ 8.40 (d, J = 8.4 Hz, 1H), 7.59 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H), 7.39 (d) , J = 8.8 Hz, 1H), 4.19 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.04 (t, J = 7.6 Hz, 2H), 1.84 (quin, J = 7.2 Hz, 2H) ), 1.55 (quin, J = 6.8 Hz, 2H), 1.27-1.40 (br, 15H); MS.m/z 420.2, [M+Na] + .

實例3-製備(8-乙氧基喹啉-2-基)及(8-異丙氧基喹啉-2-基)烷基醇Example 3 - Preparation of (8-ethoxyquinolin-2-yl) and (8-isopropoxyquinolin-2-yl)alkyl alcohol

試劑與條件：(a)碘乙烷或2-溴丙烷，K2CO3,DMF,60℃,14h.；(b)1)LHMDS,THF,0℃,1h.；2)Br(CH2)n-1OH,RT,12-30h。 Reagents and conditions : (a) ethyl iodide or 2-bromopropane, K 2 CO 3 , DMF, 60 ° C, 14 h.; (b) 1) LHMDS, THF, 0 ° C, 1 h.; 2) Br (CH 2 ) n-1 OH, RT, 12-30h.

方法：於60℃下將碘乙烷(3.9g,25.0mmol)或2-溴丙烷(2.4g,19.2mmol)添加至含2-甲基喹吶啶(3.0g,18.8mmol)及K2CO3(6.5g,47mmol；5.2g,37.6mmol)之30ml DMF攪拌溶液14小時。將反應混合物以H2O(200ml)驟冷並以EtOAc(50ml X 2)萃取。於真空下將有機層蒸發濃縮。將殘餘物 利用快速管柱層析法以Hex/EA(6：1)進行純化，並以己烷/EA再結晶以獲得固態中間體8-乙氧基-2-甲基喹啉(2.75g,78%)和液態的8-異丙氧基-2-甲基喹啉(2.92g,77%)。將LHMDS(2.2當量)以不同中間體(1當量)之攪拌溶液之THF溶液於0℃下處理1小時。將對應的Br(CH2)n-1OH(1.1-1.2當量)添加至反應混合物，並使溫度回到RT再進行12至30小時。減壓移除溶劑。將棕色油狀殘餘物利用快速管柱層析法以Hex/EA或DCM/EA進行純化，並以己烷/EA再結晶以提供化合物D及E。 Method : Ethyl iodide (3.9 g, 25.0 mmol) or 2-bromopropane (2.4 g, 19.2 mmol) was added to 2-methylquinacridine (3.0 g, 18.8 mmol) and K 2 CO at 60 °C. 3 (6.5 g, 47 mmol; 5.2 g, 37.6 mmol) of 30 ml of DMF was stirred for 14 hours. The reaction mixture was H 2 O (200ml) and quenched extracted with EtOAc (50ml X 2). The organic layer was concentrated by evaporation under vacuum. The residue was purified by flash column chromatography eluting with Hex / EA (6:1) and recrystallized from hexane/EA to give solid intermediate 8-ethoxy-2-methylquinoline (2.75 g) , 78%) and liquid 8-isopropoxy-2-methylquinoline (2.92 g, 77%). LHMDS (2.2 eq.) was treated with a solution of a mixture of different intermediates (1 eq.) in THF at 0 ° C for 1 hour. The corresponding Br(CH 2 ) n-1 OH (1.1-1.2 equivalents) was added to the reaction mixture and the temperature was returned to RT for another 12 to 30 hours. The solvent was removed under reduced pressure. The brown oily residue was purified by flash column chromatography to Hex / EA or DCM / EA was purified with hexane / EA to provide a recrystallized Compound D and E.

9-(8-乙氧基喹啉-2-基)壬-1-醇(D1)9-(8-ethoxyquinolin-2-yl)indol-1-ol (D1)

YD：45%.1H NMR(400MHz,CDCl3)δ8.07(d,J=8.0Hz,1H),7.34-7.42(m,3H),7.06(d,J=8.4Hz,1H),4.35(q,J=6.8Hz,2H),3.63(t,J=6.8Hz,2H),3.11(br,2H),1.83(quin,J=7.6Hz,2H),1.52-1.64(m,5H),1.26-1.46(br,11H)；MS.m/z 338.0,[M+Na]+。 YD: 45%. 1 H NMR (400MHz, CDCl 3 ) δ 8.07 (d, J = 8.0 Hz, 1H), 7.34-7.42 (m, 3H), 7.06 (d, J = 8.4 Hz, 1H), 4.35 (q, J = 6.8 Hz, 2H), 3.63 (t, J = 6.8 Hz, 2H), 3.11 (br, 2H), 1.83 (quin, J = 7.6 Hz, 2H), 1.52-1.64 (m, 5H) , 1.26-1.46 (br, 11H); MS.m/z 338.0, [M+Na] + .

10-(8-乙氧基喹啉-2-基)癸-1-醇(D2)10-(8-ethoxyquinolin-2-yl)indol-1-ol (D2)

YD：36%.1H NMR(400MHz,d4-MeOD)δ8.16(d,J=8.4Hz,1H),7.38-7.44(m,3H),7.14(dd,J=7.2,1.6Hz,1H),4.29(q,J=6.8Hz,2H),3.52(t,J=6.8Hz,2H),2.99(t,J=7.6Hz,2H),1.78(quin,J=7.6Hz,2H),1.57(t,J=7.6Hz,3H),1.50(t,J=7.6Hz,2H),1.30-1.43(br,13H)；MS.m/z 352.0,[M+Na]+。 YD: 36%. 1 H NMR (400MHz, d4 -MeOD) δ 8.16 (d, J = 8.4 Hz, 1H), 7.38-7.44 (m, 3H), 7.14 (dd, J = 7.2, 1.6 Hz, 1H ), 4.29 (q, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.57 (t, J = 7.6 Hz, 3H), 1.50 (t, J = 7.6 Hz, 2H), 1.30-1.43 (br, 13H); MS.m/z 352.0, [M+Na] + .

11-(8-乙氧基喹啉-2-基)十一-1-醇(D3)11-(8-ethoxyquinolin-2-yl)undec-1-ol (D3)

YD：43%.1H NMR(400MHz,CDCl3)δ8.03(d,J=7.6Hz,1H),7.31-7.41(m,3H),7.04(d,J=7.2Hz,1H),4.33(q,J=7.2Hz,2H),3.62(t,J=6.4Hz,2H),3.06(br,2H),1.81(quin,J=8.0Hz,2H),1.51-1.61(m,6H),1.38-1.51(br,14H)；MS.m/z 344.3,[M+H]+。 YD: 43%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (d, J = 7.6 Hz, 1H), 7.31 - 7.41 (m, 3H), 7.04 (d, J = 7.2 Hz, 1H), 4.33 (q, J = 7.2 Hz, 2H), 3.62 (t, J = 6.4 Hz, 2H), 3.06 (br, 2H), 1.81 (quin, J = 8.0 Hz, 2H), 1.51-1.61 (m, 6H) , 1.38-1.51 (br, 14H); MS.m/z 344.3, [M+H] + .

12-(8-乙氧基喹啉-2-基)十二-1-醇(D4)12-(8-ethoxyquinolin-2-yl)dodec-1-ol (D4)

YD：33%.1H NMR(400MHz,CDCl3)δ8.03(d,J=8.4Hz,1H),7.31-7.39(m, 3H),7.04(d,J=7.6Hz,1H),4.33(q,J=6.8Hz,2H),3.62(t,J=6.4Hz,2H),3.05(t,J=8.0Hz,2H),1.82(quin,J=7.2Hz,2H),,1.53-1.62(m,5H),1.27-1.42(br,17H)；MS.m/z 380.3,[M+Na]+。 YD: 33%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.03 (d, J = 8.4 Hz, 1H), 7.31-7.39 (m, 3H), 7.04 (d, J = 7.6 Hz, 1H), 4.33 (q, J = 6.8 Hz, 2H), 3.62 (t, J = 6.4 Hz, 2H), 3.05 (t, J = 8.0 Hz, 2H), 1.82 (quin, J = 7.2 Hz, 2H),, 1.53- 1.62 (m, 5H), 1.27-1.42 (br, 17H); MS.m/z 380.3, [M+Na] + .

13-(8-乙氧基喹啉-2-基)十三-1-醇(D5)13-(8-ethoxyquinolin-2-yl)tridec-1-ol (D5)

YD：43%.1H NMR(400MHz,CDCl3)δ8.04(d,J=8.4Hz,1H),7.32-7.40(m,3H),7.04(d,J=7.6Hz,1H),4.34(q,J=6.8Hz,2H),3.62(t,J=6.4Hz,2H),3.07(t,J=8.0Hz,2H),1.82(quin,J=7.6Hz,2H),1.52-1.62(m,5H),1.19-1.46(br,19H)；MS.m/z 394.0,[M+Na]+。 YD: 43%. 1 H NMR (400MHz, CDCl 3 ) δ 8.04 (d, J = 8.4 Hz, 1H), 7.32-7.40 (m, 3H), 7.04 (d, J = 7.6 Hz, 1H), 4.34 (q, J = 6.8 Hz, 2H), 3.62 (t, J = 6.4 Hz, 2H), 3.07 (t, J = 8.0 Hz, 2H), 1.82 (quin, J = 7.6 Hz, 2H), 1.52-1.62 (m, 5H), 1.19-1.46 (br, 19H); MS.m/z 394.0, [M+Na] + .

14-(8-乙氧基喹啉-2-基)十四-1-醇(D6)14-(8-ethoxyquinolin-2-yl)tetradec-1-ol (D6)

YD：35%.1H NMR(400MHz,CDCl3)δ8.00(d,J=8.4Hz,1H),7.28-7.35(m,3H),7.02(d,J=7.2Hz,1H),4.32(q,J=6.8Hz,2H),3.61(t,J=6.4Hz,2H),3.01(t,J=8.0Hz,2H),1.80(quin,J=7.6Hz,2H),1.52-1.60(m,5H),1.24-1.41(br,21H)；MS.m/z 408.3,[M+Na]+。 YD: 35%. 1 H NMR (400MHz, CDCl 3 ) δ 8.00 (d, J = 8.4 Hz, 1H), 7.28-7.35 (m, 3H), 7.02 (d, J = 7.2 Hz, 1H), 4.32 (q, J = 6.8 Hz, 2H), 3.61 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.52-1.60 (m, 5H), 1.24-1.41 (br, 21H); MS.m/z 408.3, [M+Na] + .

15-(8-乙氧基喹啉-2-基)十五-1-醇(D7)15-(8-ethoxyquinolin-2-yl)pentadecan-1-ol (D7)

YD：33%.1H NMR(400MHz,d4-MeOD)δ8.21(d,J=8.4Hz,1H),7.40-7.47(m,3H),7.17(dd,J=7.2,1.6Hz,1H),4.30(q,J=7.2Hz,2H),3.52(t,J=6.8Hz,2H),3.01(t,J=7.6Hz,2H),1.78(quin,J=7.6Hz,2H),1.57(t,J=6.8Hz,3H),1.51(quin,J=6.8Hz,2H),1.26-1.43(br,23H)；MS.m/z 400.4,[M+Na]+。 YD: 33%. 1 H NMR (400MHz, d4 -MeOD) δ 8.21 (d, J = 8.4 Hz, 1H), 7.40-7.47 (m, 3H), 7.17 (dd, J = 7.2, 1.6 Hz, 1H) ), 4.30 (q, J = 7.2 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.57 (t, J = 6.8 Hz, 3H), 1.51 (quin, J = 6.8 Hz, 2H), 1.26-1.43 (br, 23H); MS.m/z 400.4, [M+Na] + .

11-(8-乙氧基-5-甲基喹啉-2-基)十一-1-醇(D8)11-(8-ethoxy-5-methylquinolin-2-yl)undec-1-ol (D8)

YD：34%.1H NMR(400MHz,CDCl3)δ8.20(d,J=8.8Hz,1H),7.36(d,J=8.4Hz,1H),7.19(d,J=7.6Hz,1H),6.94(d,J=8.0Hz,1H),4.31(q,J=6.8Hz,2H),3.63(t,J=6.4Hz,2H),3.08(t,J=8.0Hz,2H),2.57(s,3H),1.83(quin,J=7.6Hz,2H),1.83(t,J=7.6Hz,3H),1.57(quin,J=7.2Hz,2H),1.41-1.45(m,2H),1.28-1.33(br,13H)；MS.m/z 380.2,[M+Na]+。 YD: 34%. 1 H NMR (400MHz, CDCl 3 ) δ 8.20 (d, J = 8.8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 7.19 (d, J = 7.6 Hz, 1H) ), 6.94 (d, J = 8.0 Hz, 1H), 4.31 (q, J = 6.8 Hz, 2H), 3.63 (t, J = 6.4 Hz, 2H), 3.08 (t, J = 8.0 Hz, 2H), 2.57(s,3H), 1.83 (quin, J = 7.6 Hz, 2H), 1.83 (t, J = 7.6 Hz, 3H), 1.57 (quin, J = 7.2 Hz, 2H), 1.41-1.45 (m, 2H) ), 1.28-1.33 (br, 13H); MS.m/z 380.2, [M+Na] + .

11-(8-乙氧基-5-氟喹啉-2-基)十一-1-醇(D9)11-(8-ethoxy-5-fluoroquinolin-2-yl)undec-1-ol (D9)

YD：49%.1H NMR(400MHz,d4-MeOD)δ8.33(d,J=8.4Hz,1H),7.49(d,J =8.8Hz,1H),7.12(t,J=9.2Hz,1H),7.05(dd,J=8.4,4.8Hz,1H),4.25(q,J=7.2Hz,2H),3.51(t,J=6.8Hz,2H),2.99(t,J=8.0Hz,2H),1.77(quin,J=7.2Hz,2H),1.55(t,J=7.2Hz,3H),1.48-1.52(m,2H),1.28-1.46(br,15H)；MS.m/z 384.2,[M+Na]+。 YD: 49%. 1 H NMR (400MHz, d4 -MeOD) δ 8.33 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.8 Hz, 1H), 7.12 (t, J = 9.2 Hz, 1H), 7.05 (dd, J = 8.4, 4.8 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 3.51 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.2 Hz, 2H), 1.55 (t, J = 7.2 Hz, 3H), 1.48-1.52 (m, 2H), 1.28-1.46 (br, 15H); MS.m/z 384.2, [M+Na] + .

9-(5-氯-8-乙氧基喹啉-2-基)壬-1-醇(D10)9-(5-chloro-8-ethoxyquinolin-2-yl)indol-1-ol (D10)

YD：34%.1H NMR(400MHz,d4-MeOD)δ8.47(d,J=8.8Hz,1H),7.55(d,J=8.8Hz,1H),7.50(d,J=8.4Hz,1H),7.10(d,J=8.8Hz,1H),4.28(q,J=6.8Hz,2H),3.51(t,J=6.4Hz,2H),3.01(t,J=8.0Hz,2H),1.76(quin,J=7.6Hz,2H),1.56(t,J=6.8Hz,3H),1.48-1.51(m,2H),1.31-1.46(br,11H)；MS.m/z 350.2,[M+H]+。 YD: 34%. 1 H NMR (400MHz, d4 -MeOD) δ 8.47 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.8 Hz, 1H), 4.28 (q, J = 6.8 Hz, 2H), 3.51 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H) , 1.76 (quin, J = 7.6 Hz, 2H), 1.56 (t, J = 6.8 Hz, 3H), 1.48-1.51 (m, 2H), 1.31-1.46 (br, 11H); MS.m/z 350.2, [M+H] + .

11-(5-氯-8-乙氧基喹啉-2-基)十一-1-醇(D11)11-(5-chloro-8-ethoxyquinolin-2-yl)undec-1-ol (D11)

YD：38%.1H NMR(400MHz,CDCl3)δ8.35(d,J=8.8Hz,1H),7.36(dd,J=8.4,3.6Hz,1H),7.19(d,J=2.4Hz,1H),6.88(d,J=8.4Hz,1H),4.25(q,J=7.2Hz,2H),3.56(t,J=6.4Hz,2H),2.98(t,J=8.0Hz,2H),1.76(quin,J=8.0Hz,2H),1.45-1.54(m,5H),1.19-1.39(br,15H)；MS.m/z 400.2,[M+Na]+。 YD: 38%. 1 H NMR (400MHz, CDCl 3 ) δ 8.35 (d, J = 8.8 Hz, 1H), 7.36 (dd, J = 8.4, 3.6 Hz, 1H), 7.19 (d, J = 2.4 Hz) , 1H), 6.88 (d, J = 8.4 Hz, 1H), 4.25 (q, J = 7.2 Hz, 2H), 3.56 (t, J = 6.4 Hz, 2H), 2.98 (t, J = 8.0 Hz, 2H) ), 1.76 (quin, J = 8.0 Hz, 2H), 1.45-1.54 (m, 5H), 1.19-1.39 (br, 15H); MS.m/z 400.2, [M+Na] + .

15-(5-氯-8-乙氧基喹啉-2-基)十五-1-醇(D12)15-(5-chloro-8-ethoxyquinolin-2-yl)pentadecan-1-ol (D12)

YD：38%.1H NMR(400MHz,d4-MeOD+CDCl3)δ8.47(d,J=8.8Hz,1H),7.53(d,J=8.8Hz,1H),7.49(d,J=8.4Hz,1H),7.08(d,J=8.4Hz,1H),4.28(q,J=6.8Hz,2H),3.52(t,J=6.8Hz,2H),3.01(t,J=8.0Hz,2H),1.79(quin,J=7.6Hz,2H),1.57(t,J=6.8Hz,3H),1.49(quin,J=6.8Hz,2H),1.25-1.41(br,23H)；MS.m/z 434.3,[M+H]+。 YD: 38%. 1 H NMR (400MHz, d4 -MeOD + CDCl 3 ) δ 8.47 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 4.28 (q, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 8.0 Hz) , 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.57 (t, J = 6.8 Hz, 3H), 1.49 (quin, J = 6.8 Hz, 2H), 1.25-1.41 (br, 23H); MS .m/z 434.3, [M+H] + .

11-(5-溴-8-乙氧基喹啉-2-基)十一-1-醇(D13)11-(5-Bromo-8-ethoxyquinolin-2-yl)undec-1-ol (D13)

YD：33%.1H NMR(400MHz,d4-MeOD)δ 8.41(d,J=8.8Hz,1H),7.67(d,J=8.4Hz,1H),7.52(d,J=8.8Hz,1H),7.04(d,J=8.4Hz,1H),4.27(q,J=7.2Hz,2H),3.52(t,J=6.8Hz,2H),3.00(t,J=8.0Hz,2H),1.77(quin,J=7.6Hz,2H),1.56(t,J=7.2Hz,3H),1.47-1.57(m,2H),1.27-1.39(br,15H)；MS.m/z 444.2,[M+Na]+。 YD: 33%. 1 H NMR (400MHz, d4 -MeOD) δ 8.41 (d, J = 8.8 Hz, 1H), 7.67 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H) ), 7.04 (d, J = 8.4 Hz, 1H), 4.27 (q, J = 7.2 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.6 Hz, 2H), 1.56 (t, J = 7.2 Hz, 3H), 1.47-1.57 (m, 2H), 1.27-1.39 (br, 15H); MS.m/z 444.2, [ M+Na] + .

11-(5,7-二氯-8-乙氧基喹啉-2-基)十一-1-醇(D14)11-(5,7-Dichloro-8-ethoxyquinolin-2-yl)undec-1-ol (D14)

YD：34%.1H NMR(400MHz,d4-MeOD)δ8.43(d,J=8.8Hz,1H),7.64(s,1H),7.51(d,J=8.4Hz,1H),4.39(q,J=6.8Hz,2H),3.52(t,J=6.8Hz,2H),3.00(t,J=7.2Hz,2H),1.84(quin,J=7.2Hz,2H),1.45-1.49(m,5H),1.27-1.36(br,15H)；MS.m/z 434.2,[M+Na]+。 YD: 34%. 1 H NMR (400MHz, d4 -MeOD) δ 8.43 (d, J = 8.8 Hz, 1H), 7.64 (s, 1H), 7.51 (d, J = 8.4 Hz, 1H), 4.39 ( q, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 7.2 Hz, 2H), 1.84 (quin, J = 7.2 Hz, 2H), 1.45-1.49 ( m, 5H), 1.27-1.36 (br, 15H); MS.m/z 434.2, [M+Na] + .

9-(8-異丙氧基喹啉-2-基)壬-1-醇(E1)9-(8-isopropoxyquinolin-2-yl)indol-1-ol (E1)

YD：28%.1H NMR(400MHz,d4-MeOD)δ 8.07(d,J=8.8Hz,1H),7.33-7.36(m,1H),7.31-7.33(m,2H),7.09(d,J=7.2Hz,1H),4.79(m,1H),3.49(t,J=6.8Hz,2H),2.93(t,J=7.6Hz,2H),1.71(quin,J=7.6Hz,2H),1.45-1.49(m,2H),1.41(d,J=6Hz,6H),1.20-1.35(br,11H)；MS.m/z 330.2,[M+H]+。 YD: 28%. 1 H NMR (400MHz, d4 -MeOD) δ 8.07 (d, J = 8.8 Hz, 1H), 7.33 - 7.36 (m, 1H), 7.31 - 7.33 (m, 2H), 7.09 (d, J = 7.2 Hz, 1H), 4.79 (m, 1H), 3.49 (t, J = 6.8 Hz, 2H), 2.93 (t, J = 7.6 Hz, 2H), 1.71 (quin, J = 7.6 Hz, 2H) , 1.45-1.49 (m, 2H), 1.41 (d, J = 6 Hz, 6H), 1.20-1.35 (br, 11H); MS.m/z 330.2, [M+H] + .

10-(8-異丙氧基喹啉-2-基)癸-1-醇(E2)10-(8-isopropoxyquinolin-2-yl)indol-1-ol (E2)

YD：36%.1H NMR(400MHz,d4-MeOD)δ 8.14(d,J=8.8Hz,1H),7.40-7.43(m,1H),7.37-7.39(m,2H),7.16(dd,J=6.8,2.0Hz,1H),4.83(m,1H),3.51(t,J=6.8Hz,2H),2.98(t,J=7.6Hz,2H),1.77(quin,J=7.2Hz,2H),1.45-1.49(m,2H),1.41(d,J=6Hz,6H),1.20-1.35(br,11H)；MS.m/z 366.0,[M+Na]+。 YD: 36%. 1 H NMR (400MHz, d4 -MeOD) δ 8.14 (d, J = 8.8 Hz, 1H), 7.40-7.43 (m, 1H), 7.37-7.39 (m, 2H), 7.16 (dd, J = 6.8, 2.0 Hz, 1H), 4.83 (m, 1H), 3.51 (t, J = 6.8 Hz, 2H), 2.98 (t, J = 7.6 Hz, 2H), 1.77 (quin, J = 7.2 Hz, 2H), 1.45-1.49 (m, 2H), 1.41 (d, J = 6 Hz, 6H), 1.20-1.35 (br, 11H); MS.m/z 366.0, [M+Na] + .

11-(8-異丙氧基喹啉-2-基)十一-1-醇(E3)11-(8-isopropoxyquinolin-2-yl)undec-1-ol (E3)

YD：45%.1H NMR(400MHz,CDCl3)δ7.99(d,J=8.4Hz,1H),7.34(d,J=4.4Hz,2H),7.24-7.27(m,1H),7.09(t,J=4.4Hz,1H),4.82(sept,J=6Hz,1H),3.60(t,J=6.8Hz,2H),3.00(t,J=7.6Hz,2H),1.81(quin,J=7.6Hz,2H),1.51-1.56(m,2H),1.47(d,J=6Hz,6H),1.33-1.43(br,15H)；MS.m/z 380.3,[M+Na]+。 YD: 45%. 1 H NMR (400MHz, CDCl 3 ) δ 7.99 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 4.4 Hz, 2H), 7.24 - 7.27 (m, 1H), 7.09 (t, J = 4.4 Hz, 1H), 4.82 (sept, J = 6 Hz, 1H), 3.60 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 1.81 (quin, J = 7.6 Hz, 2H), 1.51-1.56 (m, 2H), 1.47 (d, J = 6 Hz, 6H), 1.33-1.43 (br, 15H); MS.m/z 380.3, [M+Na] + .

12-(8-異丙氧基喹啉-2-基)十二-1-醇(E4)12-(8-isopropoxyquinolin-2-yl)dodec-1-ol (E4)

YD：34%.1H NMR(400MHz,CDCl3)δ8.05(d,J=7.6Hz,1H),7.30-7.39(m,3H),7.13(dd,J=6.4,2.4Hz,1H),4.85(sept,J=6Hz,1H),3.63(t,J=6.8Hz,2H),3.09(br,2H),1.84(quin,J=7.6Hz,2H),1.56(quin,J=7.2Hz,2H),1.48 (d,J=6Hz,6H),1.27-1.47(br,17H)；MS.m/z 394.3,[M+Na]+。 YD:. 34% 1 H NMR (400MHz, CDCl 3) δ8.05 (d, J = 7.6Hz, 1H), 7.30-7.39 (m, 3H), 7.13 (dd, J = 6.4,2.4Hz, 1H) , 4.85 (sept, J = 6 Hz, 1H), 3.63 (t, J = 6.8 Hz, 2H), 3.09 (br, 2H), 1.84 (quin, J = 7.6 Hz, 2H), 1.56 (quin, J = 7.2) Hz, 2H), 1.48 (d, J = 6 Hz, 6H), 1.27-1.47 (br, 17H); MS.m/z 394.3, [M+Na] + .

13-(8-異丙氧基喹啉-2-基)十三-1-醇(E5)13-(8-isopropoxyquinolin-2-yl)tridec-1-ol (E5)

YD：34%.1H NMR(400MHz,d4-MeOD)δ 8.11(d,J=8.4Hz,1H),7.35-7.41(m,3H),7.14(d,J=7.2Hz,1H),4.81(br,1H),3.52(t,J=6.8Hz,2H),2.96(t,J=8.0Hz,2H),1.75(quin,J=7.2Hz,2H),1.45-1.52(m,2H),1.43(d,J=6.0Hz,6H),1.25-1.42(br,19H)；MS.m/z 408.0,[M+Na]+。 YD: 34%. 1 H NMR (400MHz, d4 -MeOD) δ 8.11 (d, J = 8.4 Hz, 1H), 7.35-7.41 (m, 3H), 7.14 (d, J = 7.2 Hz, 1H), 4.81 (br,1H), 3.52 (t, J = 6.8 Hz, 2H), 2.96 (t, J = 8.0 Hz, 2H), 1.75 (quin, J = 7.2 Hz, 2H), 1.45-1.52 (m, 2H) , 1.43 (d, J = 6.0 Hz, 6H), 1.25-1.42 (br, 19H); MS.m/z 408.0, [M+Na] + .

14-(8-異丙氧基喹啉-2-基)十四-1-醇(E6)14-(8-Isopropoxyquinolin-2-yl)tetradec-1-ol (E6)

YD：36%.1H NMR(400MHz,d4-MeOD)δ8.13(d,J=8.8Hz,1H),7.37-7.43(m,3H),7.16(dd,J=7.2,1.6Hz,1H),4.86(br,1H),3.52(t,J=6.8Hz,2H),2.98(t,J=7.6Hz,2H),1.78(quin,J=7.6Hz,2H),1.49-1.52(m,2H),1.46(d,J=6.4Hz,6H),1.26-1.41(br,21H)；MS.m/z 422.3,[M+Na]+。 YD: 36%. 1 H NMR (400MHz, d4 -MeOD) δ 8.13 (d, J = 8.8 Hz, 1H), 7.37-7.43 (m, 3H), 7.16 (dd, J = 7.2, 1.6 Hz, 1H) ), 4.86 (br, 1H), 3.52 (t, J = 6.8 Hz, 2H), 2.98 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.49-1.52 (m) , 2H), 1.46 (d, J = 6.4 Hz, 6H), 1.26-1.41 (br, 21H); MS.m/z 422.3, [M+Na] + .

15-(8-異丙氧基喹啉-2-基)十五-1-醇(E7)15-(8-isopropoxyquinolin-2-yl)pentadecan-1-ol (E7)

YD：36%.1H NMR(400MHz,CDCl3)δ8.01(d,J=8.4Hz,1H),7.27-7.36(m,3H),7.10-7.13(m,1H),4.82(sept,J=4.1Hz,1H),3.61(t,J=6.8Hz,2H),3.00(t,J=6.4Hz,2H),1.81(quin,J=7.6Hz,2H),1.52-1.55(m,2H),1.48(d,J=2Hz,6H),1.31-1.47(br,21H)；MS.m/z 436.3,[M+Na]+。 YD: 36%. 1 H NMR (400MHz, CDCl 3 ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.27-7.36 (m, 3H), 7.10-7.13 (m, 1H), 4.82 (sept, J = 4.1 Hz, 1H), 3.61 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 6.4 Hz, 2H), 1.81 (quin, J = 7.6 Hz, 2H), 1.52-1.55 (m, 2H), 1.48 (d, J = 2 Hz, 6H), 1.31-1.47 (br, 21H); MS.m/z 436.3, [M+Na] + .

11-(8-異丙氧基-5-甲基喹啉-2-基)十一-1-醇(E8)11-(8-Isopropoxy-5-methylquinolin-2-yl)undec-1-ol (E8)

YD：48%.1H NMR(400MHz,CDCl3)δ8.09(d,J=8.4Hz,1H),7.26(d,J=8.8Hz,1H),7.12(d,J=8.0Hz,1H),6.97(t,J=7.6Hz,1H),4.75(sept,J=6Hz,1H),3.55(t,J=6.8Hz,2H),3.00(t,J=7.6Hz,2H),2.51(s,3H),1.81(t,J=7.2Hz,2H),1.23-1.49(br,23H)；MS.m/z 394.3,[M+Na]+。 YD: 48%. 1 H NMR (400MHz, CDCl 3 ) δ 8.09 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 8.8 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H) ), 6.97 (t, J = 7.6 Hz, 1H), 4.75 (sept, J = 6 Hz, 1H), 3.55 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 2.51 (s, 3H), 1.81 (t, J = 7.2 Hz, 2H), 1.23-1.49 (br, 23H); MS.m/z 394.3, [M+Na] + .

11-(5-氟-8-異丙氧基喹啉-2-基)十一-1-醇(E9)11-(5-Fluoro-8-isopropoxyquinolin-2-yl)undec-1-ol (E9)

YD：46%.1H NMR(400MHz,d4-MeOD)δ8.30(d,J=8.8Hz,1H),7.44(d,J=8.4Hz,1H),7.09(d,J=4.8Hz,1H),4.79(m,1H),3.51(t,J=6.8Hz,2H),2.97(t,J=8.0Hz,2H),1.74(quin,J=7.6Hz,2H),1.45-1.51(m,2H),1.42(d, J=6.4Hz,6H),1.12-1.39(br,15H)；MS.m/z 398.2,[M+Na]+。 YD: 46%. 1 H NMR (400MHz, d4 -MeOD) δ 8.30 (d, J = 8.8 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.09 (d, J = 4.8 Hz, 1H), 4.79 (m, 1H), 3.51 (t, J = 6.8 Hz, 2H), 2.97 (t, J = 8.0 Hz, 2H), 1.74 (quin, J = 7.6 Hz, 2H), 1.45-1.51 ( m, 2H), 1.42 (d, J = 6.4 Hz, 6H), 1.12-1.39 (br, 15H); MS.m/z 398.2, [M+Na] + .

9-(5-氯-8-異丙氧基喹啉-2-基)壬-1-醇(E10)9-(5-chloro-8-isopropoxyquinolin-2-yl)indol-1-ol (E10)

YD：46%.1H NMR(400MHz,d4-MeOD)δ8.45(d,J=8.8Hz,1H),7.52(d,J=8.4Hz,1H),7.49(d,J=8.4Hz,1H),7.12(d,J=8.4Hz,1H),4.85(m,1H),3.51(t,J=6.4Hz,2H),3.01(t,J=8.0Hz,2H),1.78(quin,J=7.6Hz,2H),1.49(quin,J=6.4Hz,2H),1.45(d,J=6.0Hz,6H),1.30-1.42(br,11H)；MS.m/z 364.2,[M+H]+。 YD: 46%. 1 H NMR (400MHz, d4 -MeOD) δ 8.45 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 4.85 (m, 1H), 3.51 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.49 (quin, J = 6.4 Hz, 2H), 1.45 (d, J = 6.0 Hz, 6H), 1.30-1.42 (br, 11H); MS.m/z 364.2, [M +H] + .

11-(5-氯-8-異丙氧基喹啉-2-基)十一-1-醇(E11)11-(5-chloro-8-isopropoxyquinolin-2-yl)undec-1-ol (E11)

YD：46%.1H NMR(400MHz,d4-MeOD)δ8.47(d,J=8.4Hz,1H),7.53(d,J=8.4Hz,1H),7.50(d,J=8.4Hz,1H),7.13(d,J=8.4Hz,1H),4.89(m,1H),3.52(t,J=6.4Hz,2H),3.01(t,J=7.2Hz,2H),1.79(quin,J=7.6Hz,2H),1.48(quin,J=6.8Hz,2H),1.41(d,J=5.6Hz,6H),1.21-1.39(br,15H)；MS.m/z 414.2,[M+Na]+。 YD: 46%. 1 H NMR (400MHz, d4 -MeOD) δ 8.47 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 4.89 (m, 1H), 3.52 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 7.2 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.48 (quin, J = 6.8 Hz, 2H), 1.41 (d, J = 5.6 Hz, 6H), 1.21-1.39 (br, 15H); MS.m/z 414.2, [M +Na] + .

15-(5-氯-8-異丙氧基喹啉-2-基)十五-1-醇(E12)15-(5-chloro-8-isopropoxyquinolin-2-yl)pentadecan-1-ol (E12)

YD：46%.1H NMR(400MHz,d4-MeOD+CDCl3)δ8.46(d,J=8.8Hz,1H),7.51(d,J=8.8Hz,1H),7.48(d,J=8.8Hz,1H),7.11(d,J=8.4Hz,1H),4.85(m,1H),3.52(t,J=6.8Hz,2H),3.01(t,J=8.0Hz,2H),1.79(quin,J=7.2Hz,2H),1.51(quin,J=6.8Hz,2H),1.46(d,J=6.0Hz,6H),1.25-1.39(m,23H)；MS.m/z 448.3,[M+H]+。 YD: 46%. 1 H NMR (400MHz, d4 -MeOD + CDCl 3 ) δ 8.46 (d, J = 8.8 Hz, 1H), 7.51 (d, J = 8.8 Hz, 1H), 7.48 (d, J = 8.8 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 4.85 (m, 1H), 3.52 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.79 (quin, J = 7.2 Hz, 2H), 1.51 (quin, J = 6.8 Hz, 2H), 1.46 (d, J = 6.0 Hz, 6H), 1.25-1.39 (m, 23H); MS.m/z 448.3 , [M+H] + .

11-(5-溴-8-異丙氧基喹啉-2-基)十一-1-醇(E13)11-(5-Bromo-8-isopropoxyquinolin-2-yl)undec-1-ol (E13)

YD：40%.1H NMR(400MHz,d4-MeOD)δ8.43(d,J=8.8Hz,1H),7.69(d,J=8.8Hz,1H),7.52(d,J=8.4Hz,1H),7.10(d,J=7.6Hz,1H),4.86(br,1H),3.52(t,J=6.8Hz,2H),3.02(t,J=7.6Hz,2H),1.79(quin,J=7.2Hz,2H),1.50-1.52(m,2H),1.46(d,J=6.0Hz,6H),1.28-1.41(br,15H)；MS.m/z 458.2,[M+Na]+。 YD: 40%. 1 H NMR (400MHz, d4 -MeOD) δ 8.43 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 7.6 Hz, 1H), 4.86 (br, 1H), 3.52 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 7.6 Hz, 2H), 1.79 (quin, J = 7.2 Hz, 2H), 1.50-1.52 (m, 2H), 1.46 (d, J = 6.0 Hz, 6H), 1.28-1.41 (br, 15H); MS.m/z 458.2, [M+Na] + .

11-(5,7-二氯-8-異丙氧基喹啉-2-基)十一-1-醇(E14)11-(5,7-Dichloro-8-isopropoxyquinolin-2-yl)undec-1-ol (E14)

YD：37%.1H NMR(400MHz,CDCl3)δ8.36(d,J=8.4Hz,1H),7.56(d,J=3.2Hz,1H),7.35(d,J=8.4Hz,1H),5.13(m,1H),3.63(t,J=6.8Hz,2H),3.00(t,J=7.6Hz,2H),1.86(quin,J=6.8Hz,2H),1.52-1.59(m,4H),1.27-1.44(br,20H)；MS.m/z 448.4,[M+Na]+。 YD: 37%. 1 H NMR (400MHz, CDCl 3 ) δ 8.36 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 3.2 Hz, 1H), 7.35 (d, J = 8.4 Hz, 1H) ), 5.13 (m, 1H), 3.63 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 1.86 (quin, J = 6.8 Hz, 2H), 1.52-1.59 (m , 4H), 1.27-1.44 (br, 20H); MS.m/z 448.4, [M+Na] + .

實例4-製備(8-環丙基甲氧基喹啉-2-基)烷基醇衍生物Example 4 - Preparation of (8-cyclopropylmethoxyquinolin-2-yl)alkyl alcohol derivative

試劑與條件：(a)亞甲基環丙基溴，K2CO3,DMF,60℃,13h.；(b)1)LHMDS,THF,0℃,1h.；2)Br(CH2)n-1OH,rt,12-20h。 Reagents and conditions : (a) methylene cyclopropyl bromide, K 2 CO 3 , DMF, 60 ° C, 13 h.; (b) 1) LHMDS, THF, 0 ° C, 1 h.; 2) Br (CH 2 ) N-1 OH, rt, 12-20h.

方法：於60℃下將亞甲基環丙基溴(1.0g,6.3mmol)添加至含2-甲基喹吶啶(1.0g,6.3mmol)及K2CO3(2.5g,18.1mmol)攪拌溶液之25ml DMF中13小時。將反應混合物以H2O(200ml)驟冷並以EtOAc(30ml X 3)萃取。於真空下將有機層蒸發濃縮，並將殘餘物利用快速管柱層析法以Hex/EA(8：1至6：1)進行純化以提供中間體5-氯-8-(環丙基甲氧基)-2-甲基喹啉。將LHMDS(2.2當量)以含中間體(0.5g,2.3mmol)攪拌溶液之THF溶液於0℃下處理1小時。將對應的Br(CH2)n-1OH(1.1-1.2當量)添加至反應混合物，並使溫度回到RT再進行12至20小時。減壓移除溶劑。將棕色油狀殘餘物利用快速管柱層析法以Hex/EA或DCM/EA進行純化，並以Hex/EA再結晶以提供化合物F。 Method : Methylenecyclopropyl bromide (1.0 g, 6.3 mmol) was added to 2-methylquinacridine (1.0 g, 6.3 mmol) and K 2 CO 3 (2.5 g, 18.1 mmol) at 60 °C. The solution was stirred in 25 ml of DMF for 13 hours. The reaction mixture was H 2 O (200ml) and quenched extracted with EtOAc (30ml X 3). The organic layer was concentrated by evaporation <RTI ID=0.0></RTI></RTI><RTIID=0.0></RTI> Oxy)-2-methylquinoline. LHMDS (2.2 eq.) was treated with a solution of intermediate (0.5 g, 2. The corresponding Br(CH 2 ) n-1 OH (1.1-1.2 equivalents) was added to the reaction mixture and the temperature was returned to RT for another 12 to 20 hours. The solvent was removed under reduced pressure. The brown oily residue was purified by flash column chromatography using Hex / EA or DCM / EA and recrystallised from Hex / EA to afford compound F.

9-(8-(環丙基甲氧基)喹啉-2-基)壬-1-醇(F1)9-(8-(cyclopropylmethoxy)quinolin-2-yl)indol-1-ol (F1)

YD：49%.1H NMR(400MHz,d4-MeOD)δ8.15(d,J=8.4Hz,1H),7.38-7.43 (m,3H),7.14(dd,J=5.6,3.2Hz,1H),4.06(d,J=7.2Hz,2H),3.51(t,J=6.8Hz,2H),3.00(t,J=8.0Hz,2H),1.77(quin,J=7.6Hz,2H),1.48-1.52(m,3H),1.32-1.47(m,11H),0.65-0.70(m,2H),0.34-0.45(m,2H)；MS.m/z 342.2,[M+H]+。 YD: 49%. 1 H NMR (400MHz, d4 -MeOD) δ 8.15 (d, J = 8.4 Hz, 1H), 7.38-7.43 (m, 3H), 7.14 (dd, J = 5.6, 3.2 Hz, 1H ), 4.06 (d, J = 7.2 Hz, 2H), 3.51 (t, J = 6.8 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H), 1.77 (quin, J = 7.6 Hz, 2H), 1.48-1.52 (m, 3H), 1.32-1.47 (m, 11H), 0.65-0.70 (m, 2H), 0.34-0.45 (m, 2H); MS.m/z 342.2, [M+H] + .

10-(8-(環丙基甲氧基)喹啉-2-基)癸-1-醇(F2)10-(8-(cyclopropylmethoxy)quinolin-2-yl)indol-1-ol (F2)

YD：43%.1H NMR(400MHz,d4-MeOD)δ8.16(d,J=8.4Hz,1H),7.40~7.43(m,3H),7.15(dd,J=5.6,3.2Hz,1H),4.07(d,J=7.2Hz,2H),3.52(t,J=6.4Hz,2H),3.01(t,J=8.0Hz,2H),1.80(quin,J=7.6Hz,2H),1.47-1.53(m,3H),1.31-1.44(m,13H),0.67-0.69(m,2H),0.44-0.46(m,2H)；MS.m/z 356.2,[M+H]+。 YD: 43%. 1 H NMR (400MHz, d4 -MeOD) δ 8.16 (d, J = 8.4 Hz, 1H), 7.40~7.43 (m, 3H), 7.15 (dd, J = 5.6, 3.2 Hz, 1H ), 4.07 (d, J = 7.2 Hz, 2H), 3.52 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 8.0 Hz, 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.47-1.53 (m, 3H), 1.31-1.44 (m, 13H), 0.67-0.69 (m, 2H), 0.44-0.46 (m, 2H); MS.m/z 356.2, [M+H] + .

11-(8-(環丙基甲氧基)喹啉-2-基)十一-1-醇(F3)11-(8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol (F3)

YD：45%.1H NMR(400MHz,CDCl3)δ8.02(d,J=8.4Hz,1H),7.30~7.38(m,2H),7.05(dd,J=6.4,2.4Hz,1H),4.11(d,J=6.8Hz,1H),3.63(t,J=6.4Hz,2H),3.04(t,J=8.0Hz,2H),1.83(quin,J=7.6Hz,2H),1.48-1.59(m,3H),1.26-1.46(br,15H),0.67(dd,J=13.2,5.6Hz,2H),0.44(dd,J=13.2,5.6Hz,2H)；MS.m/z 392.2,[M+Na]+。 YD: 45%. 1 H NMR (400MHz, CDCl 3 ) δ 8.02 (d, J = 8.4 Hz, 1H), 7.30 to 7.38 (m, 2H), 7.05 (dd, J = 6.4, 2.4 Hz, 1H) , 4.11 (d, J = 6.8 Hz, 1H), 3.63 (t, J = 6.4 Hz, 2H), 3.04 (t, J = 8.0 Hz, 2H), 1.83 (quin, J = 7.6 Hz, 2H), 1.48 -1.59 (m, 3H), 1.26-1.46 (br, 15H), 0.67 (dd, J = 13.2, 5.6 Hz, 2H), 0.44 (dd, J = 13.2, 5.6 Hz, 2H); MS.m/z 392.2, [M+Na] + .

12-(8-(環丙基甲氧基)喹啉-2-基)十二-1-醇(F4)12-(8-(cyclopropylmethoxy)quinolin-2-yl)dodec-1-ol (F4)

YD：36%.1H NMR(400MHz,CDCl3)δ8.01(d,J=8.4Hz,1H),7.29-7.38(m,3H),7.06(dd,J=6.0,2.4Hz,1H),4.11(d,J=6.8Hz,1H),3.63(t,J=6.4Hz,2H),3.04(t,J=7.2Hz,2H),1.83(quin,J=7.6Hz,2H),1.48-1.59(m,3H),1.27-1.47(br,17H),0.67(dd,J=13.2,5.6Hz,2H),0.42-0.48(m,2H)；MS.m/z 384.3,[M+H]+。 YD: 36%. 1 H NMR (400MHz, CDCl 3 ) δ 8.01 (d, J = 8.4 Hz, 1H), 7.29-7.38 (m, 3H), 7.06 (dd, J = 6.0, 2.4 Hz, 1H) , 4.11 (d, J = 6.8 Hz, 1H), 3.63 (t, J = 6.4 Hz, 2H), 3.04 (t, J = 7.2 Hz, 2H), 1.83 (quin, J = 7.6 Hz, 2H), 1.48 -1.59 (m, 3H), 1.27-1.47 (br, 17H), 0.67 (dd, J = 13.2, 5.6 Hz, 2H), 0.42-0.48 (m, 2H); MS.m/z 384.3, [M+ H] + .

13-(8-(環丙基甲氧基)喹啉-2-基)十三-1-醇(F5)13-(8-(cyclopropylmethoxy)quinolin-2-yl)tridec-1-ol (F5)

YD：42%.1H NMR(400MHz,d4-MeOD)δ8.14(d,J=8.4Hz,1H),7.38~7.41(m,3H),7.05(dd,J=5.6,3.2Hz,1H),4.05(d,J=6.8Hz,2H),3.52(t,J=6.4Hz,2H),2.99(t,J=8.0Hz,2H),1.78(quin,J=7.6Hz,2H),1.44-1.52(m, 3H),1.26-1.40(m,19H),0.67(dd,J=13.2,5.6Hz,2H),0.40-0.47(m,2H)；MS.m/z 420.0,[M+Na]+。 YD: 42%. 1 H NMR (400MHz, d4 -MeOD) δ 8.14 (d, J = 8.4 Hz, 1H), 7.38~7.41 (m, 3H), 7.05 (dd, J = 5.6, 3.2 Hz, 1H ), 4.05 (d, J = 6.8 Hz, 2H), 3.52 (t, J = 6.4 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.44-1.52 (m, 3H), 1.26-1.40 (m, 19H), 0.67 (dd, J = 13.2, 5.6 Hz, 2H), 0.40-0.47 (m, 2H); MS.m/z 420.0, [M +Na] + .

14-(8-(環丙基甲氧基)喹啉-2-基)十四-1-醇(F6)14-(8-(cyclopropylmethoxy)quinolin-2-yl)tetradec-1-ol (F6)

YD：37%.1H NMR(400MHz,d4-MeOD)δ8.15(d,J=8.8Hz,1H),7.39~7.42(m,3H),7.13(dd,J=5.6,3.2Hz,1H),4.05(d,J=6.8Hz,2H),3.52(t,J=6.8Hz,2H),2.99(t,J=7.6Hz,2H),1.78(quin,J=7.6Hz,2H),1.44-1.52(m,3H),1.26-1.43(m,21H),0.65-0.69(m,2H),0.42(dd,J=10.0,4.8Hz,2H)；MS.m/z 434.3,[M+Na]+。 YD: 37%. 1 H NMR (400MHz, d4 -MeOD) δ 8.15 (d, J = 8.8 Hz, 1H), 7.39~7.42 (m, 3H), 7.13 (dd, J = 5.6, 3.2 Hz, 1H ), 4.05 (d, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz, 2H), 1.78 (quin, J = 7.6 Hz, 2H), 1.44-1.52 (m, 3H), 1.26-1.43 (m, 21H), 0.65-0.69 (m, 2H), 0.42 (dd, J = 10.0, 4.8 Hz, 2H); MS.m/z 434.3, [M +Na] + .

15-(8-(環丙基甲氧基)喹啉-2-基)十五-1-醇(F7)15-(8-(cyclopropylmethoxy)quinolin-2-yl)pentadecan-1-ol (F7)

YD：69%.1H NMR(400MHz,d4-MeOD+CDCl3)δ8.13(dd,J=8.4,2.0Hz,1H),7.38(br,3H),7.11(d,J=2.4Hz,1H),4.05(d,J=6.8Hz,2H),3.52(t,J=6.8Hz,2H),2.99(t,J=8.0Hz,2H),1.78(quin,J=7.2Hz,2H),1.46-1.52(m,3H),1.25-1.44(m,23H),0.63-0.69(m,2H),0.40-0.46(m,2H)；MS.m/z 426.4,[M+H]+。 YD: 69%. 1 H NMR (400MHz, d4 -MeOD + CDCl 3 ) δ 8.13 (dd, J = 8.4, 2.0 Hz, 1H), 7.38 (br, 3H), 7.11 (d, J = 2.4 Hz, 1H), 4.05 (d, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 8.0 Hz, 2H), 1.78 (quin, J = 7.2 Hz, 2H) , 1.46-1.52 (m, 3H), 1.25-1.44 (m, 23H), 0.63-0.69 (m, 2H), 0.40-0.46 (m, 2H); MS.m/z 426.4, [M+H] + .

11-(8-(環丙基甲氧基)-5-甲基喹啉-2-基)十一-1-醇(F8)11-(8-(cyclopropylmethoxy)-5-methylquinolin-2-yl)undec-1-ol (F8)

YD：45%.1H NMR(400MHz,d4-MeOD)δ8.31(d,J=8.8Hz,1H),δ 7.44(d,J=8.8Hz,1H),7.22(d,J=8.0Hz,1H),7.02(d,J=8.0Hz,1H),4.02(d,J=7.2Hz,2H),3.52(t,J=6.4Hz,2H),3.00(t,J=8.0Hz,2H),2.57(s,3H),1.79(quin,J=7.2Hz,2H),1.29-1.52(m,18H),0.65-0.68(m,2H),0.40-0.43(m,2H)；MS.m/z 406.3,[M+Na]+。 YD: 45%. 1 H NMR (400MHz, d4 -MeOD) δ 8.31 (d, J = 8.8 Hz, 1H), δ 7.44 (d, J = 8.8 Hz, 1H), 7.22 (d, J = 8.0 Hz) , 1H), 7.02 (d, J = 8.0 Hz, 1H), 4.02 (d, J = 7.2 Hz, 2H), 3.52 (t, J = 6.4 Hz, 2H), 3.00 (t, J = 8.0 Hz, 2H) ), 2.57 (s, 3H), 1.79 (quin, J = 7.2 Hz, 2H), 1.29-1.52 (m, 18H), 0.65-0.68 (m, 2H), 0.40-0.43 (m, 2H); m/z 406.3, [M+Na] + .

11-(8-(環丙基甲氧基)-5-氟喹啉-2-基)十一-1-醇(F9)11-(8-(cyclopropylmethoxy)-5-fluoroquinolin-2-yl)undec-1-ol (F9)

YD：46%.1H NMR(400MHz,d4-MeOD)δ8.36(d,J=8.8Hz,1H),7.52(d,J=8.8Hz,1H),7.07-7.15(m,2H),4.05(d,J=6.8Hz,2H),3.53(t,J=6.8Hz,2H),3.02(t,J=7.6Hz,2H),1.79(quin,J=7.6Hz,2H),1.42-1.49(m,3H),1.22-1.40(m,15H),0.65-0.69(m,2H),0.42(dd,J=10.4,4.8Hz,2H)；MS.m/z 410.2,[M+Na]+。 YD: 46%. 1 H NMR (400MHz, d4 -MeOD) δ 8.36 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.07-7.15 (m, 2H), 4.05 (d, J = 6.8 Hz, 2H), 3.53 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 7.6 Hz, 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.42 1.49 (m, 3H), 1.22-1.40 (m, 15H), 0.65-0.69 (m, 2H), 0.42 (dd, J = 10.4, 4.8 Hz, 2H); MS.m/z 410.2, [M+Na ] + .

9-(5-氯-8-(環丙基甲氧基)喹啉-2-基)壬-1-醇(F10)9-(5-chloro-8-(cyclopropylmethoxy)quinolin-2-yl)indol-1-ol (F10)

YD：33%.1H NMR(400MHz,d4-MeOD)δ8.48(d,J=8.8Hz,1H),7.55(d,J=8.8Hz 1H),7.49(d,J=8.4Hz,1H),7.11(d,J=8.4Hz,1H),4.06(d,J=6.8Hz,2H),3.51(t,J=6.4Hz,2H),3.03(t,J=8.0Hz,2H),1.83(t,J=7.6Hz,2H),1.54-1.69(m,3H),1.27-1.48(br,15H),0.67-0.71(m,2H),0.43-0.46(m,2H)；MS.m/z 376.2,[M+H]+。 YD: 33%. 1 H NMR (400MHz, d4 -MeOD) δ 8.48 (d, J = 8.8 Hz, 1H), 7.55 (d, J = 8.8 Hz 1H), 7.49 (d, J = 8.4 Hz, 1H) ), 7.11 (d, J = 8.4 Hz, 1H), 4.06 (d, J = 6.8 Hz, 2H), 3.51 (t, J = 6.4 Hz, 2H), 3.03 (t, J = 8.0 Hz, 2H), 1.83 (t, J = 7.6 Hz, 2H), 1.54-1.69 (m, 3H), 1.27-1.48 (br, 15H), 0.67-0.71 (m, 2H), 0.43-0.46 (m, 2H); MS. m/z 376.2, [M+H] + .

11-(5-氯-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇(F11)11-(5-chloro-8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol (F11)

YD：34%.1H NMR(400MHz,CDCl3)δ8.41(d,J=8.8Hz,1H),7.43(d,J=2.4Hz 1H),7.41(d,J=2.4Hz,1H),6.97(d,J=8.4Hz,1H),4.09(d,J=7.2Hz,2H),3.63(t,J=6.4Hz,2H),3.05(t,J=8.0Hz,2H),1.83(t,J=7.6Hz,2H),1.54-1.69(m,3H),1.27-1.48(br,15H),0.67-0.71(m,2H),0.43-0.46(m,2H)；MS.m/z 426.2,[M+Na]+。 YD: 34%. 1 H NMR (400MHz, CDCl 3 ) δ 8.41 (d, J = 8.8 Hz, 1H), 7.43 (d, J = 2.4 Hz 1H), 7.41 (d, J = 2.4 Hz, 1H) , 6.97 (d, J = 8.4 Hz, 1H), 4.09 (d, J = 7.2 Hz, 2H), 3.63 (t, J = 6.4 Hz, 2H), 3.05 (t, J = 8.0 Hz, 2H), 1.83 (t, J = 7.6 Hz, 2H), 1.54-1.69 (m, 3H), 1.27-1.48 (br, 15H), 0.67-0.71 (m, 2H), 0.43-0.46 (m, 2H); MS.m /z 426.2, [M+Na] + .

15-(5-氯-8-(環丙基甲氧基)喹啉-2-基)十五-1-醇(F12)15-(5-chloro-8-(cyclopropylmethoxy)quinolin-2-yl)pentadecan-1-ol (F12)

YD：28%.1H NMR(400MHz,d4-MeOD+CDCl3)δ8.47(d,J=8.8Hz,1H),7.54(d,J=8.8Hz,1H),7.48(d,J=8.4Hz,1H),7.10(d,J=8.4Hz,1H),4.06(d,J=6.8Hz,2H),3.52(t,J=6.8Hz,2H),3.02(t,J=7.6Hz,2H),1.79(quin,J=7.6Hz,2H),1.46-1.52(m,2H),1.25-1.44(br,24H),0.65-0.69(m,2H),0.41-0.43(m,2H)；MS.m/z 460.3,[M+Na]+。 YD: 28%. 1 H NMR (400MHz, d4 -MeOD + CDCl 3 ) δ 8.47 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.10 (d, J = 8.4 Hz, 1H), 4.06 (d, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 7.6 Hz) , 2H), 1.79 (quin, J = 7.6 Hz, 2H), 1.46-1.52 (m, 2H), 1.25-1.44 (br, 24H), 0.65-0.69 (m, 2H), 0.41-0.43 (m, 2H) ); MS.m/z 460.3, [M+Na] + .

11-(5-溴-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇(F13)11-(5-Bromo-8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol (F13)

YD：35%.1H NMR(400MHz,d4-MeOD)δ8.42(d,J=8.8Hz,1H),δ 7.67(d,J=8.4Hz,1H),7.53(d,J=8.8Hz,1H),7.06(d,J=8.4Hz,1H),4.05(d,J=7.2Hz,2H),3.51(t,J=6.4Hz,2H),3.02(t,J=8.0Hz,2H),1.77(quin,J=7.6Hz,2H),1.46-1.52(m,3H),1.28-1.44(m,15H),0.65-0.70(m,2H),0.42-0.45(m,2H)；MS.m/z 470.2,[M+Na]+。 YD: 35%. 1 H NMR (400MHz, d4 -MeOD) δ 8.42 (d, J = 8.8 Hz, 1H), δ 7.67 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.8 Hz) , 1H), 7.06 (d, J = 8.4 Hz, 1H), 4.05 (d, J = 7.2 Hz, 2H), 3.51 (t, J = 6.4 Hz, 2H), 3.02 (t, J = 8.0 Hz, 2H) ), 1.77 (quin, J = 7.6 Hz, 2H), 1.46-1.52 (m, 3H), 1.28-1.44 (m, 15H), 0.65-0.70 (m, 2H), 0.42-0.45 (m, 2H); MS.m/z 470.2, [M+Na] + .

11-(5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇(F14)11-(5,7-Dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol (F14)

YD：53%.1H NMR(400MHz,d4-MeOD)δ8.47(d,J=8.8Hz,1H),δ 7.67(s, 1H),7.53(d,J=8.8Hz,1H),7.06(d,J=8.4Hz,1H),4.23(d,J=7.2Hz,2H),3.53(t,J=6.4Hz,2H),3.02(t,J=7.6Hz,2H),1.86(quin,J=7.2Hz,2H),1.48-1.53(m,2H),1.29-1.38(m,16H),0.62(dd,J=12.8,5.2Hz,2H),0.31(dd,J=10.8,5.2Hz,2H)；MS.m/z 460.2,[M+Na]+。 YD: 53%. 1 H NMR (400MHz, d4 -MeOD) δ 8.47 (d, J = 8.8 Hz, 1H), δ 7.67 (s, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 4.23 (d, J = 7.2 Hz, 2H), 3.53 (t, J = 6.4 Hz, 2H), 3.02 (t, J = 7.6 Hz, 2H), 1.86 (quin , J = 7.2 Hz, 2H), 1.48-1.53 (m, 2H), 1.29-1.38 (m, 16H), 0.62 (dd, J = 12.8, 5.2 Hz, 2H), 0.31 (dd, J = 10.8, 5.2 Hz, 2H); MS.m/z 460.2, [M+Na] + .

實例5-製備(5,7-二氯-8-羥基喹啉-2-基)烷基醇Example 5 - Preparation of (5,7-dichloro-8-hydroxyquinolin-2-yl)alkyl alcohol

試劑與條件：(a)NCS,CHCl3,rt,48h。 Reagents and conditions : (a) NCS, CHCl 3 , rt, 48 h.

方法：將N-氯琥珀醯亞胺(0.3g,2.25mmol)添加至含有化合物B攪拌溶液之CHCl3(20ml)中48小時。將反應混合物倒入碎冰中並以CH2Cl2(20ml X 2)萃取。將萃取物利用管柱層析法以Hex/EA(3：1)進行純化，並再結晶以獲得化合物G1(0.18g,49%)。 Method: N- chlorosuccinimide (PEI) (0.3g, 2.25mmol) was added to a stirred solution containing compound B of CHCl 3 (20ml) 48 hours. The reaction mixture was poured into crushed ice and extracted with CH 2 Cl 2 (20 mL). The extract was purified by column chromatography using Hex/EA (3:1) and recrystallized to afford compound G1 (0.18 g, 49%).

5,7-二氯-2-(11-羥十一基)喹啉-8-醇(G1)5,7-dichloro-2-(11-hydroxyundecyl)quinolin-8-ol (G1)

YD：49%.1H NMR(400MHz,CDCl3)δ8.38(d,J=8.8Hz,1H),7.51(s,1H),7.42(d,J=8.8Hz,1H),3.63(t,J=6.8Hz,2H),3.00(t,J=7.6Hz,2H),1.82(quin,J=7.2Hz,2H),1.56(quin,J=7.6Hz,2H),1.27-1.38(br,15H)；MS.m/z 382.0,[M-H]+。 YD: 49%. 1 H NMR (400MHz, CDCl 3 ) δ 8.38 (d, J = 8.8 Hz, 1H), 7.51 (s, 1H), 7.42 (d, J = 8.8 Hz, 1H), 3.63 (t , J = 6.8 Hz, 2H), 3.00 (t, J = 7.6 Hz, 2H), 1.82 (quin, J = 7.2 Hz, 2H), 1.56 (quin, J = 7.6 Hz, 2H), 1.27-1.38 (br , 15H); MS.m/z 382.0, [MH] + .

實例6-製備(5-氯-8-甲氧基喹啉-2-基)烷基醇或烷基乙酸酯Example 6 - Preparation of (5-chloro-8-methoxyquinolin-2-yl)alkyl alcohol or alkyl acetate

試劑與條件：(a)HCl,ICl3，冰HOAc,H2O,6h,rt。 Reagents and conditions: (a) HCl, ICl 3 , ice HOAc, H 2 O, 6h, rt.

方法：於室溫下將濃HCl(0.5mL/mmol)添加至各種不同長鏈經取代之(8-甲氧基喹啉-2-基)-醇(1.0當量)，並將紅黃色混合物攪拌5分鐘。逐滴將ICl3(1.5當量)之濃HCl(2mL)溶液添加至此混合物中。於室溫下攪拌此黃色黏稠混合物6小時。將水加入其中並以EA進行分層。以鹽水沖洗有機層、以無水MgSO4乾燥並過濾，之後移除溶劑以獲得油狀殘餘物，將油狀殘餘物利用快速管柱層析法以CHCl3進行純化以獲得H1至H5。 Method : Concentrated HCl (0.5 mL/mmol) was added to various long-chain substituted (8-methoxyquinolin-2-yl)-ols (1.0 eq.) at room temperature, and the red-yellow mixture was stirred. 5 minutes. Dropwise ICl 3 (1.5 eq.) Of concentrated HCl (2mL) was added to the mixture. The yellow viscous mixture was stirred at room temperature for 6 hours. Water was added to it and stratified with EA. The organic layer was washed with brine, dried and filtered over anhydrous MgSO 4, then the solvent was removed to obtain an oily residue, and the oily residue was purified by flash column chromatography using CHCl 3 method to obtain H1 to H5.

10-(5-氯-8-甲氧基喹啉-2-基)癸-1-醇(H1a)及乙酸10-(5-氯-8-甲氧基喹啉-2-基)癸酯(H1b)10-(5-chloro-8-methoxyquinolin-2-yl)indol-1-ol (H1a) and 10-(5-chloro-8-methoxyquinolin-2-yl)decyl acetate (H1b)

YD：61%及10%.H1a： 1H NMR(200MHz,CDCl3)δ8.41(d,J=8.68Hz,1H),7.42(dd,J=8Hz,J=2Hz,2H),6.91(d,J=8Hz,1H),4.03(s,3H),3.59(t,J=6Hz,2H),3.59(t,J=4Hz,2H),1.73(m,2H),1.48(m,2H),1.25(br,12H)；HRMS(EI)：計算值C20H28ClNO2：349.1803，實際值：349.1781.H1b： 1H NMR(400MHz,CDCl3)δ8.41(d,J=8Hz,1H),7.42(dd,J=8Hz,J=4Hz,2H),6.92(d,J=8Hz,1H),4.06(t,J=8Hz,2H),4.02(s,3H),3.03(t,J=8Hz,2H),2.02(s,3H),1.79(m,2H),1.59(m,2H),1.40(m,2H),1.23(br,12H)；HRMS(FAB,M+H)：計算值C22H31ClNO3 392.1992，實際值392.1983。 YD: 61% and 10%. H1a: 1 H NMR (200MHz, CDCl 3 ) δ 8.41 (d, J = 8.68 Hz, 1H), 7.42 (dd, J = 8 Hz, J = 2 Hz, 2H), 6.91 ( d, J = 8 Hz, 1H), 4.03 (s, 3H), 3.59 (t, J = 6 Hz, 2H), 3.59 (t, J = 4 Hz, 2H), 1.73 (m, 2H), 1.48 (m, 2H) ), 1.25 (br, 12H) ; HRMS (EI):. calculated for C 20 H 28 ClNO 2: 349.1803 , actual value: 349.1781 H1b: 1 H NMR ( 400MHz, CDCl 3) δ8.41 (d, J = 8Hz , 1H), 7.42 (dd, J = 8 Hz, J = 4 Hz, 2H), 6.92 (d, J = 8 Hz, 1H), 4.06 (t, J = 8 Hz, 2H), 4.02 (s, 3H), 3.03 ( t, J=8 Hz, 2H), 2.02 (s, 3H), 1.79 (m, 2H), 1.59 (m, 2H), 1.40 (m, 2H), 1.23 (br, 12H); HRMS (FAB, M+) H): Calcd. for C 22 H 31 ClNO 3 392.1992, 391.1983.

11-(5-氯-8-甲氧基喹啉-2-基)十一-1-醇(H2a)及乙酸11-(5-氯-8-甲氧基喹啉-2-基)十一酯(H2b)11-(5-chloro-8-methoxyquinolin-2-yl)undec-1-ol (H2a) and 11-(5-chloro-8-methoxyquinolin-2-yl)acetate Monoester (H2b)

YD：60%及12%.H2a： 1H NMR(400MHz,CDCl3)δ8.43(d,J=8.72Hz,1H),7.44(dd,J=13.5Hz,J=5.3Hz,2H),6.94(d,J=8.3Hz,1H),4.05(s,3H),3.62(t,J=6.6Hz,2H),3.07(t,J=5.2Hz,2H),1.80(m,2H),1.54(m,2H),1.39(m,2H),1.26(br,12H)；HRMS(EI)：計算值C21H30ClNO2 363.1960，實 際值363.1941.H2b： 1H NMR(400MHz,CDCl3)δ8.41(d,J=8.6Hz,1H),7.42(dd,J=8.3Hz,J=3.8Hz,2H),6.91(d,J=8.4Hz,1H),4.06(t,J=7.8Hz,2H),4.02(s,3H),3.02(t,J=7.8Hz,2H),2.01(s,3H),1.78(m,2H),1.58(m,2H),1.39(m,2H),1.22(br,12H)；HRMS(EI)：計算值C23H32ClNO3 405.2065,實際值405.2044。 YD: 60% and 12% H2a:. 1 H NMR (400MHz, CDCl 3) δ8.43 (d, J = 8.72Hz, 1H), 7.44 (dd, J = 13.5Hz, J = 5.3Hz, 2H), 6.94 (d, J = 8.3 Hz, 1H), 4.05 (s, 3H), 3.62 (t, J = 6.6 Hz, 2H), 3.07 (t, J = 5.2 Hz, 2H), 1.80 (m, 2H), 1.54 (m, 2H), 1.39 (m, 2H), 1.26 (br, 12H); HRMS (EI): Calculated C 21 H 30 ClNO 2 363.1960, actual value 363.1941. H2b: 1 H NMR (400 MHz, CDCl 3 ) δ 8.41 (d, J = 8.6 Hz, 1H), 7.42 (dd, J = 8.3 Hz, J = 3.8 Hz, 2H), 6.91 (d, J = 8.4 Hz, 1H), 4.06 (t, J = 7.8 Hz, 2H), 4.02 (s, 3H), 3.02 (t, J = 7.8 Hz, 2H), 2.01 (s, 3H), 1.78 (m, 2H), 1.58 (m, 2H), 1.39 (m, 2H), 1.22 (br, 12H); HRMS (EI): calcd for C 23 H 32 ClNO 3 405.2065.

12-(5-氯-8-甲氧基喹啉-2-基)十二-1-醇(H3a)及乙酸12-(5-氯-8-甲氧基喹啉-2-基)十二酯(H3b)12-(5-chloro-8-methoxyquinolin-2-yl)dodec-1-ol (H3a) and 12-(5-chloro-8-methoxyquinolin-2-yl)acetate Diester (H3b)

YD：57%及27%.H3a： 1H NMR(400MHz,CDCl3)δ8.46(d,J=8.6Hz,1H),7.44(dd,J=8.3Hz,J=6.9Hz,2H),6.94(d,J=8.4Hz,1H),4.04(s,3H),3.59(t,J=6.6Hz,2H),3.11(t,J=7.8Hz,2H),1.78(m,2H),1.50(m,2H),1.40(m,2H),1.23(br,14H)；HRMS(EI)：計算值C22H32ClNO2 377.2116，實際值377.2106.H3b： 1H NMR(200MHz,CDCl3)δ8.38(d,J=8.7Hz,1H),7.40(d,J=8.6Hz,2H),6.88(d,J=8.4Hz,1H),4.03(t,J=7.8Hz,2H),4.01(s,3H),3.02(t,J=7.8Hz,2H),1.99(s,3H),1.76(m,2H),1.59(m,2H),1.20(br,16H)；HRMS(FAB,M+H)：計算值C24H35ClNO3 420.2305，實際值420.2310。 YD: 57% and 27%. H3a: 1 H NMR (400MHz, CDCl 3 ) δ 8.46 (d, J = 8.6 Hz, 1H), 7.44 (dd, J = 8.3 Hz, J = 6.9 Hz, 2H), 6.94 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 3.59 (t, J = 6.6 Hz, 2H), 3.11 (t, J = 7.8 Hz, 2H), 1.78 (m, 2H), 1.50 (m, 2H), 1.40 (m, 2H), 1.23 (br, 14H); HRMS (EI): Calculated C 22 H 32 ClNO 2 377.2116, actual value 377.2106. H3b: 1 H NMR (200 MHz, CDCl 3 ) δ 8.38 (d, J = 8.7 Hz, 1H), 7.40 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.4 Hz, 1H), 4.03 (t, J = 7.8 Hz, 2H) , 4.01 (s, 3H), 3.02 (t, J = 7.8 Hz, 2H), 1.99 (s, 3H), 1.76 (m, 2H), 1.59 (m, 2H), 1.20 (br, 16H); HRMS ( FAB, M + H): Calcd C 24 H 35 ClNO 3 420.2305, 420.2310 actual value.

13-(5-氯-8-甲氧基喹啉-2-基)十三-1-醇(H4a)及乙酸13-(5-氯-8-甲氧基喹啉-2-基)十三酯(H4b)13-(5-chloro-8-methoxyquinolin-2-yl)tridec-1-ol (H4a) and 13-(5-chloro-8-methoxyquinolin-2-yl)acetate Triester (H4b)

YD：64%及14%.H4a： 1H NMR(400MHz,CDCl3)δ8.46(d,J=8.6Hz,1H),7.45(dd,J=8.3Hz,J=6.9Hz,2H),6.94(d,J=8.4Hz,1H),4.04(s,3H),3.59(t,J=6.6Hz,2H),3.11(t,J=7.8Hz,2H),1.78(m,2H),1.50(m,2H),1.40(m,2H),1.23(br,16H)；HRMS(EI)：計算值C23H34ClNO2 391.2273，實際值391.2249.H4b： 1H NMR(400MHz,CDCl3)δ 8.38(d,J=8.6Hz,1H),7.40(dd,J=8.5Hz,J=5.8Hz,2H),6.89(d,J=8.4Hz,1H),4.01(t,J=9.6Hz,2H),4.00(s,3H),3.00(t,J=7.9Hz,2H),1.99(s,3H),1.75(m,2H),1.58(m,2H),1.38(m,2H),1.22(br,16H)；HRMS(FAB,M+H)：計算值C25H37ClNO3 434.2462，實際值434.2459。 YD: 64% and 14%. H4a: 1 H NMR (400MHz, CDCl 3 ) δ 8.46 (d, J = 8.6 Hz, 1H), 7.45 (dd, J = 8.3 Hz, J = 6.9 Hz, 2H), 6.94 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 3.59 (t, J = 6.6 Hz, 2H), 3.11 (t, J = 7.8 Hz, 2H), 1.78 (m, 2H), 1.50 (m, 2H), 1.40 (m, 2H), 1.23 (br, 16H); HRMS (EI): Calculated C 23 H 34 ClNO 2 391.2273, actual value 391.2249. H4b: 1 H NMR (400 MHz, CDCl 3 ) δ 8.38 (d, J = 8.6 Hz, 1H), 7.40 (dd, J = 8.5 Hz, J = 5.8 Hz, 2H), 6.89 (d, J = 8.4 Hz, 1H), 4.01 (t, J = 9.6) Hz, 2H), 4.00 (s, 3H), 3.00 (t, J = 7.9 Hz, 2H), 1.99 (s, 3H), 1.75 (m, 2H), 1.58 (m, 2H), 1.38 (m, 2H) ), 1.22 (br, 16H); HRMS (FAB, M+H): calcd for C 25 H 37 ClNO 3 434.2462, actual value 434.2459.

實例7-製備(8-羥基喹啉-4-基)或(8-烷氧基喹啉-4-基)烷基醇Example 7 - Preparation of (8-hydroxyquinolin-4-yl) or (8-alkoxyquinolin-4-yl)alkyl alcohol

試劑與條件：(a)甲基乙烯基酮，HCl，回流.(b)MeI,K2CO3，丙酮，rt,8h；EtI或2-溴丙烷或亞甲基環丙基溴，K2CO3,DMF,60℃,(c)1)LHMDS,THF,0℃,1h.；2)Br(CH2)n-1OH,rt,(d)BnBr,KOH,EtOH，回流.(e)H2,Pd/C,MeOH,rt,24h。 Reagents and conditions : (a) methyl vinyl ketone, HCl, reflux. (b) MeI, K 2 CO 3 , acetone, rt, 8 h; EtI or 2-bromopropane or methylene cyclopropyl bromide, K 2 CO 3 , DMF, 60 ° C, (c) 1) LHMDS, THF, 0 ° C, 1 h.; 2) Br(CH 2 ) n-1 OH, rt, (d) BnBr, KOH, EtOH, reflux. H 2 , Pd/C, MeOH, rt, 24h.

方法：由2-胺基苯酚與甲基乙烯基酮之反應透過閉環反應合成中間體INT 1。將INT 1與各種鹵烷反應以提供8-烷氧基-4-甲基喹啉衍生物作為中間體。將對應的Br(CH2)n-1OH與中間體反應以合成一系列化合物J及I。利用氫化反應(該方法於實例1中說明)移除保護基J，以獲得化合物K。 Method : The intermediate INT 1 was synthesized by a ring closure reaction from the reaction of 2-aminophenol with methyl vinyl ketone. INT 1 is reacted with various haloalkanes to provide an 8-alkoxy-4-methylquinoline derivative as an intermediate. The corresponding Br(CH 2 ) n-1 OH is reacted with an intermediate to synthesize a series of compounds J and I. The protecting group J was removed using a hydrogenation reaction (this method is illustrated in Example 1 ) to obtain the compound K.

11-(8-甲氧基喹啉-4-基)十一-1-醇(I1)11-(8-methoxyquinolin-4-yl)undec-1-ol (I1)

YD：34%.1H NMR(400MHz,CDCl3)δ8.80(dd,J=4.4,0.6Hz,1H),7.59(dd,J=8.4,0.8Hz,1H),7.44-7.49(m,1H),7.03(d,J=7.6Hz,1H),4.08(s,3H),3.63(t,J=6.8Hz,2H),3.03(t,J=7.6Hz,2H),1.74(quin,J=7.6Hz,2H),1.55(quin,J=7.2Hz,2H),1.23-1.45(br,15H)；MS.m/z 329.9,[M+H]+。 YD: 34%. 1 H NMR (400MHz, CDCl 3 ) δ 8.80 (dd, J = 4.4, 0.6 Hz, 1H), 7.59 (dd, J = 8.4, 0.8 Hz, 1H), 7.44-7.49 (m, 1H), 7.03 (d, J = 7.6 Hz, 1H), 4.08 (s, 3H), 3.63 (t, J = 6.8 Hz, 2H), 3.03 (t, J = 7.6 Hz, 2H), 1.74 (quin, J = 7.6 Hz, 2H), 1.55 (quin, J = 7.2 Hz, 2H), 1.23-1.45 (br, 15H); MS.m/z 329.9, [M+H] + .

11-(8-乙氧基喹啉-4-基)十一-1-醇(I2)11-(8-ethoxyquinolin-4-yl)undec-1-ol (I2)

YD：42%.H NMR(400MHz,d4-MeOD)δ8.66(d,J=8.4Hz,1H),7.64(d,J=8.4Hz,1H),7.51(t,J=8.0Hz,1H),7.37(d,J=8.4Hz,1H),7.15(d,J=7.6Hz,1H),4.27(q,J=6.8Hz,2H),3.52(t,J=6.8Hz,2H),3.08(d,J=7.6Hz,2H),1.75(quin,J=7.6Hz,2H),1.50-1.57(m,5H),1.21-1.49(br,15H)；MS.m/z 366.2,[M+Na]+。 YD: 42%. H NMR (400MHz, d4 -MeOD) δ 8.66 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H) ), 7.37 (d, J = 8.4 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 4.27 (q, J = 6.8 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.08 (d, J = 7.6 Hz, 2H), 1.75 (quin, J = 7.6 Hz, 2H), 1.50-1.57 (m, 5H), 1.21-1.49 (br, 15H); MS.m/z 366.2, [ M+Na] + .

11-(8-異丙氧基喹啉-4-基)十一-1-醇(I3)11-(8-isopropoxyquinolin-4-yl)undec-1-ol (I3)

YD：48%.1H NMR(400MHz,d4-MeOD)δ 8.65(d,J=8.4Hz,1H),7.63(d,J=7.6Hz,1H),7.51(d,J=8.0Hz,1H),7.35(d,J=4.4Hz,1H),7.17(d,J=8.0Hz,1H),4.84(br,1H),3.52(t,J=6.4Hz,2H),3.07(d,J=7.6Hz,2H),1.74(br,2H),1.43-1.50(br,9H),1.29-1.34(br,14H)；MS.m/z 380.3,[M+Na]+。 YD: 48%. 1 H NMR (400MHz, d4 -MeOD) δ 8.65 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H) ), 7.35 (d, J = 4.4 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 4.84 (br, 1H), 3.52 (t, J = 6.4 Hz, 2H), 3.07 (d, J) = 7.6 Hz, 2H), 1.74 (br, 2H), 1.43-1.50 (br, 9H), 1.29-1.34 (br, 14H); MS.m/z 380.3, [M+Na] + .

11-(8-(環丙基甲氧基)喹啉-4-基)十一-1-醇(I4)11-(8-(cyclopropylmethoxy)quinolin-4-yl)undec-1-ol (I4)

YD：53%.1H NMR(400MHz,d4-MeOD)δ8.66(d,J=8.4Hz,1H),7.63(d,J=8.4Hz,1H),7.49(t,J=8.4Hz,1H),7.36(d,J=4.8Hz,1H),7.13(d,J=7.6Hz,1H),4.03(d,J=6.8Hz,1H),3.52(t,J=6.8Hz,2H),3.06(d,J=7.6Hz,2H),1.69-1.75(m,2H),1.28-1.52(br,18H),0.65-0.68(m,2H),0.42-0.43(m,2H)；MS.m/z 392.2[M+Na]+。 YD: 53%. 1 H NMR (400MHz, d4 -MeOD) δ 8.66 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.49 (t, J = 8.4 Hz, 1H), 7.36 (d, J = 4.8 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 4.03 (d, J = 6.8 Hz, 1H), 3.52 (t, J = 6.8 Hz, 2H) , 3.06 (d, J = 7.6 Hz, 2H), 1.69-1.75 (m, 2H), 1.28-1.52 (br, 18H), 0.65-0.68 (m, 2H), 0.42-0.43 (m, 2H); .m/z 392.2[M+Na] + .

11-(8-(苯甲氧基)喹啉-4-基)十一-1-醇(J1)11-(8-(Benzyloxy)quinolin-4-yl)undec-1-ol (J1)

YD：46%.1H NMR(400MHz,d4-MeOD)δ 8.66(d,J=8.4Hz,1H),7.64(d,J=8.4Hz,1H),7.52(d,J=7.2Hz,2H),7.45(t,J=8.0Hz,1H),7.30-7.38(m,3H),7.26-7.28(m,1H),7.17(d,J=7.6Hz,1H),5.37(s,2H),3.52(t,J=6.4Hz,2H),3.06(t,J=8Hz,2H),1.73(q,J=7.6Hz,2H),1.50(t,J=7.2Hz,2H),1.28-1.48(m,15H)；MS.m/z 428.3,[M+Na]+。 YD: 46%. 1 H NMR (400MHz, d4 -MeOD) δ 8.66 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H ), 7.45 (t, J = 8.0 Hz, 1H), 7.30-7.38 (m, 3H), 7.26-7.28 (m, 1H), 7.17 (d, J = 7.6 Hz, 1H), 5.37 (s, 2H) , 3.52 (t, J = 6.4 Hz, 2H), 3.06 (t, J = 8 Hz, 2H), 1.73 (q, J = 7.6 Hz, 2H), 1.50 (t, J = 7.2 Hz, 2H), 1.28- 1.48 (m, 15H); MS.m/z 428.3, [M+Na] + .

12-(8-(苯甲氧基)喹啉-4-基)十二-1-醇(J2)12-(8-(Benzyloxy)quinolin-4-yl)dodec-1-ol (J2)

YD：46%.1H NMR(400MHz,d4-MeOD)δ 8.67(d,J=4.4Hz,1H),7.65(d,J=8.4Hz,1H),7.52(d,J=7.2Hz,2H),7.45(t,J=8.0Hz,1H),7.30-7.39(m,3H),7.27-7.30(m,1H),7.18(d,J=8.0Hz,1H),5.38(s,2H),3.52(t,J=6.4 Hz,2H),3.08(t,J=7.6Hz,2H),1.74(q,J=7.6Hz,2H),1.49(t,J=7.2Hz,2H),1.23-1.45(m,17H)；MS.m/z 442.3,[M+Na]+。 YD: 46%. 1 H NMR (400MHz, d4 -MeOD) δ 8.67 (d, J = 4.4 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 7.2 Hz, 2H ), 7.45 (t, J = 8.0 Hz, 1H), 7.30-7.39 (m, 3H), 7.27-7.30 (m, 1H), 7.18 (d, J = 8.0 Hz, 1H), 5.38 (s, 2H) , 3.52 (t, J = 6.4 Hz, 2H), 3.08 (t, J = 7.6 Hz, 2H), 1.74 (q, J = 7.6 Hz, 2H), 1.49 (t, J = 7.2 Hz, 2H), 1.23 -1.45 (m, 17H); MS.m/z 442.3, [M+Na] + .

4-(11-羥十一基)喹啉-8-醇(K1)4-(11-hydroxyundecyl)quinolin-8-ol (K1)

YD：84%.1H NMR(400MHz,d4-MeOD)δ 8.63(d,J=4.4Hz,1H),7.51(d,J=8.4Hz,1H),7.40(t,J=8.0Hz,1H),7.28(d,J=4.0Hz,1H),7.06(d,J=7.6Hz,1H),3.51(t,J=6.8Hz,2H),3.02(t,J=8.0Hz,2H),1.71(t,J=7.6Hz,2H),1.50(quin,J=6.8Hz,2H),1.12-1.31(br,15H)；MS.m/z 316.2,[M+H]+。 YD: 84%. 1 H NMR (400MHz, d4 -MeOD) δ 8.63 (d, J = 4.4 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H) ), 7.28 (d, J = 4.0 Hz, 1H), 7.06 (d, J = 7.6 Hz, 1H), 3.51 (t, J = 6.8 Hz, 2H), 3.02 (t, J = 8.0 Hz, 2H), 1.71 (t, J = 7.6 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.12-1.31 (br, 15H); MS.m/z 316.2, [M+H] + .

4-(12-羥十二基)喹啉-8-醇(K2)4-(12-hydroxydodecyl)quinolin-8-ol (K2)

YD：86%.1H NMR(400MHz,CDCl3)δ8.52(d,J=4.4Hz,1H),7.36(dd,J=8.4,0.8Hz,1H),7.31(d,J=7.6Hz,1H),7.13(d,J=4.4Hz,1H),6.99(dd,J=7.6,1.2Hz,1H),3.43(t,J=6.8Hz,2H),2.89(t,J=7.6Hz,2H),1.61(quin,J=7.6Hz,2H),1.40(quin,J=6.8Hz,2H),1.12-1.31(br,17H)；MS.m/z 352.2,[M+Na]+。 YD: 86%. 1 H NMR (400MHz, CDCl 3 ) δ 8.52 (d, J = 4.4 Hz, 1H), 7.36 (dd, J = 8.4, 0.8 Hz, 1H), 7.31 (d, J = 7.6 Hz) , 1H), 7.13 (d, J = 4.4 Hz, 1H), 6.99 (dd, J = 7.6, 1.2 Hz, 1H), 3.43 (t, J = 6.8 Hz, 2H), 2.89 (t, J = 7.6 Hz) , 2H), 1.61 (quin, J = 7.6 Hz, 2H), 1.40 (quin, J = 6.8 Hz, 2H), 1.12-1.31 (br, 17H); MS.m/z 352.2, [M+Na] + .

實例8-製備(8-三氟甲氧基喹啉-2-基)烷基醇Example 8 - Preparation of (8-trifluoromethoxyquinolin-2-yl)alkyl alcohol

方法：將2-三氟甲氧基苯胺與巴豆醛反應以透過閉環反應合成中間體。將中間體與對應的Br(CH2)n-1OH(如上所述)反應以合成一系列化合物L。 Method : 2-Trifluoromethoxyaniline is reacted with crotonaldehyde to synthesize an intermediate by a ring closure reaction. The intermediate is reacted with the corresponding Br(CH 2 ) n-1 OH (described above) to synthesize a series of compounds L.

9-(8-(三氟甲氧基)喹啉-2-基)壬-1-醇(L1)9-(8-(Trifluoromethoxy)quinolin-2-yl)indol-1-ol (L1)

YD：41%.1H NMR(400MHz,CDCl3)δ8.06(dd,J=8.4,1.2Hz,1H),7.70(d,J=8.4Hz,1H),7.56(d,J=7.6Hz,1H),7.43(d,J=8.0Hz,1H),7.34(dd,J=8.4,1.2Hz,1H),3.61(t,J=6.4Hz,2H),3.01(t,J=6.4Hz,2H),1.81-1.85(br,2H),1.53-1.56(br,2H),1.21-1.35(m,15H)；MS.m/z 355.9,[M+H]+。 YD: 41%. 1 H NMR (400MHz, CDCl 3 ) δ 8.06 (dd, J = 8.4, 1.2 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 7.6 Hz) , 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.34 (dd, J = 8.4, 1.2 Hz, 1H), 3.61 (t, J = 6.4 Hz, 2H), 3.01 (t, J = 6.4 Hz) , 2H), 1.81-1.85 (br, 2H), 1.53-1.56 (br, 2H), 1.21-1.35 (m, 15H); MS.m/z 355.9, [M+H] + .

11-(8-(三氟甲氧基)喹啉-2-基)十一-1-醇(L2)11-(8-(Trifluoromethoxy)quinolin-2-yl)undec-1-ol (L2)

YD：41%.1H NMR(400MHz,d4-MeOD)δ8.26(t,J=8.0Hz,1H),7.86(d,J= 7.6Hz,1H),7.64(t,J=7.2Hz,1H),7.47-7.56(m,2H),3.51(t,J=6.8Hz,2H),2.99(t,J=6.4Hz,2H),1.79(quin,J=6.8Hz,2H),1.50(quin,J=6.8Hz,2H),1.21-1.35(m,15H)；MS.m/z 406.2,[M+Na]+。 YD:. 41% 1 H NMR (400MHz, d4 -MeOD) δ8.26 (t, J = 8.0Hz, 1H), 7.86 (d, J = 7.6Hz, 1H), 7.64 (t, J = 7.2Hz, 1H), 7.47-7.56 (m, 2H), 3.51 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 6.4 Hz, 2H), 1.79 (quin, J = 6.8 Hz, 2H), 1.50 ( Quin, J = 6.8 Hz, 2H), 1.21-1.35 (m, 15H); MS.m/z 406.2, [M+Na] + .

14-(8-(三氟甲氧基)喹啉-2-基)十四-1-醇(L3)14-(8-(Trifluoromethoxy)quinolin-2-yl)tetradec-1-ol (L3)

YD：37%.1H NMR(400MHz,d4-MeOD)δ 8.27(d,J=8.4Hz,1H),7.87(d,J=8.0Hz,1H),7.65(t,J=7.2Hz,1H),7.49-7.56(m,2H),3.52(t,J=6.8Hz,2H),3.01(t,J=7.6Hz,2H),1.82(quin,J=7.2Hz,2H),1.51(quin,J=6.8Hz,2H),1.27-1.37(m,21H)；MS.m/z 448.2,[M+Na]+。 YD: 37%. 1 H NMR (400MHz, d4 -MeOD) δ 8.27 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 7.2 Hz, 1H) ), 7.49-7.56 (m, 2H), 3.52 (t, J = 6.8 Hz, 2H), 3.01 (t, J = 7.6 Hz, 2H), 1.82 (quin, J = 7.2 Hz, 2H), 1.51 (quin) , J = 6.8 Hz, 2H), 1.27-1.37 (m, 21H); MS.m/z 448.2, [M+Na] + .

15-(8-(三氟甲氧基)喹啉-2-基)十五-1-醇(L4)15-(8-(trifluoromethoxy)quinolin-2-yl)pentadecan-1-ol (L4)

YD：32%.1H NMR(400MHz,d4-MeOD+CDCl3)δ8.21(d,J=8.4Hz,1H),7.81(d,J=8.0Hz,1H),7.61(d,J=7.6Hz,1H),7.51(d,J=8.0Hz,1H),7.46(t,J=8.4Hz,1H),3.52(t,J=6.8Hz,2H),2.99(t,J=7.6Hz,2H),1.80(quin,J=7.6Hz,2H),1.50(quin,J=7.2Hz,2H),1.15-1.41(br,23H)；MS.m/z 462.2,[M+Na]+。 YD: 32%. 1 H NMR (400 MHz, d4 -MeOD + CDCl 3 ) δ 8.21 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.61 (d, J = 7.6 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 8.4 Hz, 1H), 3.52 (t, J = 6.8 Hz, 2H), 2.99 (t, J = 7.6 Hz) , 2H), 1.80 (quin, J = 7.6 Hz, 2H), 1.50 (quin, J = 7.2 Hz, 2H), 1.15-1.41 (br, 23H); MS.m/z 462.2, [M+Na] + .

實例9-製備2-N-取代-8-羥基/烷氧基喹啉Example 9 - Preparation of 2-N-substituted-8-hydroxy/alkoxyquinoline

試劑與條件：(a)SeO2，二【口+咢】烷，50至80℃；(b)N-甲基丙炔胺或2-(哌【口+井】-1-基)乙醇或NH2(CH2)n-1OH,NaBH(OAc)3,1,2-二氯乙烷，rt。 Reagents and conditions : (a) SeO 2 , two [oral + oxime] alkane, 50 to 80 ° C; (b) N-methylpropynylamine or 2- (pipe [mouth + well]-1-yl) ethanol or NH 2 (CH 2 ) n -1 OH, NaBH (OAc) 3 , 1,2-dichloroethane, rt.

方法：在50℃下逐滴將8-羥基-2-甲基喹啉(6.0g,37.7mmol)之二【口+ 咢】烷(15ml)溶液添加至SeO2(6.3g,56.8mmol)之二【口+咢】烷(80ml)攪拌溶液，並將混合物加熱至80℃再20小時。過濾所形成之混合物。濃縮濾液，並將殘餘物利用管柱層析法以Hex/EA=(15：1至10：1)進行純化以獲得8-羥基喹啉-2-羧醛(2.45g,38%)衍生物作為中間體。以胺基醇、胺基炔或其他雜環，利用還原胺化反應將中間體轉化為N-取代化合物，以提供一系列化合物。將8-烷氧基-2-甲基喹啉氧化以提供8-烷氧基喹啉-2-羧醛衍生物，之後並以相同方法獲得化合物M至O。 Method : A solution of 8-hydroxy-2-methylquinoline (6.0 g, 37.7 mmol) in bis[o]+[upta]ane (15 ml) was added dropwise to a solution of SeO 2 (6.3 g, 56.8 mmol) at 50 °C. The solution was stirred for two [mouth + oxime] alkane (80 ml), and the mixture was heated to 80 ° C for another 20 hours. The resulting mixture was filtered. The filtrate was concentrated, and the residue was purified by column chromatography eluting with Hex/EA=(15:1 to 10:1) to obtain 8-hydroxyquinolin-2-carboxaldehyde (2.45 g, 38%). As an intermediate. The intermediate is converted to an N -substituted compound by a reductive amination reaction with an amino alcohol, an amino alkyne or other heterocyclic ring to provide a series of compounds. The 8-alkoxy-2-methylquinoline is oxidized to provide an 8-alkoxyquinoline-2-carboxaldehyde derivative, after which the compounds M to O are obtained in the same manner.

2-((4-(2-羥乙基)哌【口+井】-1-基)甲基)喹啉-8-醇(M1)2-((4-(2-hydroxyethyl)piperidinyl][indol]-1-yl)methyl)quinolin-8-ol (M1)

YD：76%.1H NMR(400MHz,CDCl3)δ8.02(d,J=8.4Hz,1H),7.43(d,J=8.4Hz,1H),7.34(t,J=8.0Hz,1H),7.22(d,J=7.6Hz,1H),7.10(d,J=6.8Hz,1H),3.73(s,2H),3.61(t,J=6.8Hz,2H),2.51(t,J=5.6Hz,10H)；HRMS(ESI)：計算值[M+Na]+：310.1526，實際值：310.1527。 YD: 76%. 1 H NMR (400MHz, CDCl 3 ) δ 8.02 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H) ), 7.22 (d, J = 7.6 Hz, 1H), 7.10 (d, J = 6.8 Hz, 1H), 3.73 (s, 2H), 3.61 (t, J = 6.8 Hz, 2H), 2.51 (t, J = 5.6Hz, 10H); HRMS ( ESI): Calcd [M + Na] +: 310.1526 , Found: 310.1527.

2-(4-((5-氯-8-甲氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇(M2)2-(4-((5-chloro-8-methoxyquinolin-2-yl)methyl)piperidone [mouth + well]-1-yl)ethanol (M2)

YD：76%.1H NMR(400MHz,CDCl3)δ8.23(d,J=8.8Hz,1H),7.59(d,J=8.8Hz,1H),7.21(d,J=8.4Hz,1H),6.68(d,J=8.8Hz,1H),3.81(s,3H),3.72(s,2H),3.44(t,J=4.8Hz,2H),2.35-2.38(m,10H)；MS.m/z 336.1,[M+H]+。 YD: 76%. 1 H NMR (400MHz, CDCl 3 ) δ 8.23 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.21. (d, J = 8.4 Hz, 1H ), 6.68 (d, J = 8.8 Hz, 1H), 3.81 (s, 3H), 3.72 (s, 2H), 3.44 (t, J = 4.8 Hz, 2H), 2.35-2.38 (m, 10H); MS .m/z 336.1, [M+H] + .

2-(4-((5-氯-8-乙氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇(M3)2-(4-((5-Chloro-8-ethoxyquinolin-2-yl)methyl)piperidone [mouth + well]-1-yl)ethanol (M3)

YD：53%.1H NMR(400MHz,CDCl3)δ8.36(d,J=8.8Hz,1H),7.68(d,J=8.4Hz,1H),7.34(d,J=8.4Hz,1H),6.83(d,J=8.4Hz,1H),4.18(q,J=6.8Hz,3H),3.84(s,2H),3.54(t,J=5.2Hz,2H),2.45-2.50(br,10H),1.49(t,J=6.8Hz,3H)；MS.m/z 350.1,[M+H]+。 YD: 53%. 1 H NMR (400MHz, CDCl 3 ) δ 8.36 (d, J = 8.8 Hz, 1H), 7.68 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H) ), 6.83 (d, J = 8.4 Hz, 1H), 4.18 (q, J = 6.8 Hz, 3H), 3.84 (s, 2H), 3.54 (t, J = 5.2 Hz, 2H), 2.45-2.50 (br , 10H), 1.49 (t, J = 6.8 Hz, 3H); MS.m/z 350.1, [M+H] + .

2-(4-((5-氯-8-異丙氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇(M4)2-(4-((5-chloro-8-isopropoxyquinolin-2-yl)methyl)piperidone [mouth + well]-1-yl)ethanol (M4)

YD：61%.1H NMR(400MHz,d4-MeOD)δ8.52(d,J=8.8Hz,1H),7.81(d,J=8.8Hz,1H),7.53(d,J=8.4Hz,1H),7.14(d,J=8.4Hz,1H),4.87(m,1H), 3.89(s,2H),3.67(t,J=6.0Hz,2H),2.54-2.62(br,10H),1.45(t,J=6.0Hz,6H)；MS.m/z 364.1,[M+H]+。 YD:. 61% 1 H NMR (400MHz, d4 -MeOD) δ8.52 (d, J = 8.8Hz, 1H), 7.81 (d, J = 8.8Hz, 1H), 7.53 (d, J = 8.4Hz, 1H), 7.14 (d, J = 8.4 Hz, 1H), 4.87 (m, 1H), 3.89 (s, 2H), 3.67 (t, J = 6.0 Hz, 2H), 2.54-2.62 (br, 10H), 1.45 (t, J = 6.0 Hz, 6H); MS.m/z 364.1, [M+H] + .

2-(4-((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基)哌【口+井】-1-基)乙烷(M5)2-(4-((5-chloro-8-(cyclopropylmethoxy)) quinolin-2-yl)methyl)piperidone [mouth + well]-1-yl)ethane (M5)

YD：76%.1H NMR(400MHz,d4-MeOD)δ8.40(d,J=8.4Hz,1H),7.71(d,J=8.8Hz,1H),7.42(d,J=8.4Hz,1H),6.99(d,J=8.4Hz,1H),3.97(d,J=6.8Hz,2H),3.84(s,2H),3.65(t,J=6.0Hz,2H),3.44(t,J=4.8Hz,2H),2.56(br,8H),2.51(t,J=4.8Hz,2H),1.37-1.43(m,1H),0.62-0.66(m,2H),0.37-0.40(m,2H)；MS.m/z 376.2,[M+H]+。 YD: 76%. 1 H NMR (400MHz, d4 -MeOD) δ 8.40 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 3.97 (d, J = 6.8 Hz, 2H), 3.84 (s, 2H), 3.65 (t, J = 6.0 Hz, 2H), 3.44 (t, J = 4.8 Hz, 2H), 2.56 (br, 8H), 2.51 (t, J = 4.8 Hz, 2H), 1.37-1.43 (m, 1H), 0.62-0.66 (m, 2H), 0.37-0.40 (m , 2H); MS.m/z 376.2, [M+H] + .

2-(4-((5,7-二氯-8-甲氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇(M6)2-(4-((5,7-Dichloro-8-methoxyquinolin-2-yl)methyl)piperidone [mouth + well]-1-yl)ethanol (M6)

YD：39%.1H NMR(400MHz,d4-MeOD)δ 8.53(d,J=8.8Hz,1H),7.80(d,J=8.8Hz,1H),7.70(s,1H),4.11(s,3H),3.89(s,2H),3.67(t,J=6.0Hz,2H),2.63(br,8H),2.55(t,J=6.0Hz,2H),1.93(s,1H)；MS.m/z 370.1,[M+H]+。 YD: 39%. 1 H NMR (400MHz, d4 -MeOD) δ 8.53 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.70 (s, 1H), 4.11 (s) , 3H), 3.89 (s, 2H), 3.67 (t, J = 6.0 Hz, 2H), 2.63 (br, 8H), 2.55 (t, J = 6.0 Hz, 2H), 1.93 (s, 1H); MS .m/z 370.1, [M+H] + .

2-(4-((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基)哌【口+井】-1-基)乙醇(M7)2-(4-((5,7-Dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)methyl)pipeper [mouth + well]-1-yl)ethanol (M7)

YD：82%.1H NMR(400MHz,CDCl3)δ8.43(d,J=8.8Hz,1H),7.71(d,J=8.8Hz,1H),7.58(s,1H),4.22(d,J=7.2Hz,2H),3.88(s,2H)3.61(t,J=6.4Hz,2H),2.56(t,J=5.2Hz,10H),1.41-1.44(m,1H),0.57-0.62(m,2H),0.33-0.37(m,2H)；MS.m/z 410.1,[M+Na]+。 YD: 82%. 1 H NMR (400MHz, CDCl 3 ) δ 8.43 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.58 (s, 1H), 4.22 (d) , J = 7.2 Hz, 2H), 3.88 (s, 2H) 3.61 (t, J = 6.4 Hz, 2H), 2.56 (t, J = 5.2 Hz, 10H), 1.41-1.44 (m, 1H), 0.57- 0.62 (m, 2H), 0.33-0.37 (m, 2H); MS.m/z 410.1, [M+Na] + .

2-((甲基(丙-2-炔基)胺基)甲基)喹啉-8-醇(N1)2-((methyl(prop-2-ynyl)amino)methyl)quinolin-8-ol (N1)

YD：49%.1H NMR(400MHz,CDCl3)δ8.08(d,J=8.4Hz,1H),7.55(d,J=8.4Hz,1H),7.40(t,J=8.0Hz,1H),7.28(d,J=8.0Hz,1H),7.15(d,J=7.6Hz,1H),3.90(s,2H),3.41(d,J=2.0Hz,2H),2.39(s,3H),2.31(d,J=2.0Hz,1H)；MS.m/z 249.1,[M+H]+。 YD: 49%. 1 H NMR (400MHz, CDCl 3 ) δ 8.08 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H) ), 7.28 (d, J = 8.0 Hz, 1H), 7.15 (d, J = 7.6 Hz, 1H), 3.90 (s, 2H), 3.41 (d, J = 2.0 Hz, 2H), 2.39 (s, 3H) ), 2.31 (d, J = 2.0 Hz, 1H); MS.m/z 249.1, [M+H] + .

5-氯-2-((甲基(丙-2-炔基)胺基)甲基)喹啉-8-醇(N2)5-chloro-2-((methyl(prop-2-ynyl)amino)methyl)quinolin-8-ol (N2)

YD：38%.1H NMR(400MHz,CDCl3)δ8.47(d,J=8.4Hz,1H),7.71(d,J=8.8Hz,1H),7.47(d,J=8.0Hz,1H),7.08(d,J=8.4Hz,1H),3.93(s,2H),3.42 (d,J=2.0Hz,2H),2.40(s,3H),2.31(t,J=2.0Hz,1H)；MS.m/z 261.0,[M+H]+。 YD: 38%. 1 H NMR (400MHz, CDCl 3 ) δ 8.47 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H) ), 7.08 (d, J = 8.4 Hz, 1H), 3.93 (s, 2H), 3.42 (d, J = 2.0 Hz, 2H), 2.40 (s, 3H), 2.31 (t, J = 2.0 Hz, 1H) ); MS.m/z 261.0, [M+H] + .

N-((5-氯-8-甲氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺(N3)N-((5-chloro-8-methoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine (N3)

YD：52%.1H NMR(400MHz,CDCl3)δ8.48(d,J=8.8Hz,1H),7.80(d,J=8.8Hz,1H),7.46(d,J=8.4Hz,1H),6.93(d,J=8.4Hz,1H),4.05(s,3H),4.00(s,2H),3.42(d,J=2.0Hz,2H),2.37(s,3H),2.27(t,J=2.0Hz,1H),MS.m/z 297.0,[M+Na]+。 YD: 52%. 1 H NMR (400MHz, CDCl 3 ) δ 8.48 (d, J = 8.8 Hz, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H) ), 6.93 (d, J = 8.4 Hz, 1H), 4.05 (s, 3H), 4.00 (s, 2H), 3.42 (d, J = 2.0 Hz, 2H), 2.37 (s, 3H), 2.27 (t) , J = 2.0 Hz, 1H), MS.m/z 297.0, [M+Na] + .

N-((5-氯-8-乙氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺(N4)N-((5-chloro-8-ethoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine (N4)

YD：64%.1H NMR(400MHz,CDCl3)δ8.48(d,J=8.8Hz,1H),7.79(d,J=8.8Hz,1H),7.46(d,J=8.8Hz,1H),6.96(d,J=8.4Hz,1H),4.32(t,J=6.8Hz,2H),4.01(s,2H),3.45(d,J=2.0Hz,2H),2.41(s,3H),2.28(t,J=2.0Hz,1H),1.59(t,J=6.8Hz,3H)；MS.m/z 289.1,[M+H]+。 YD: 64%. 1 H NMR (400MHz, CDCl 3 ) δ 8.48 (d, J = 8.8 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H) ), 6.96 (d, J = 8.4 Hz, 1H), 4.32 (t, J = 6.8 Hz, 2H), 4.01 (s, 2H), 3.45 (d, J = 2.0 Hz, 2H), 2.41 (s, 3H) ), 2.28 (t, J = 2.0 Hz, 1H), 1.59 (t, J = 6.8 Hz, 3H); MS.m/z 289.1, [M+H] + .

N-((5-氯-8-異丙氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺(N5)N-((5-Chloro-8-isopropoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine (N5)

YD：76%.1H NMR(400MHz,CDCl3)δ8.47(d,J=8.8Hz,1H),7.73(d,J=8.8Hz,1H),7.46(d,J=8.0Hz,1H),7.03(d,J=8.4Hz,1H),4.80(m,1H),3.99(s,2H),3.44(d,J=2.4Hz,2H),2.41(s,3H),2.28(t,J=2.4Hz,1H),1.48(d,J=6.4Hz,6H)；MS.m/z 303.1,[M+H]+。 YD: 76%. 1 H NMR (400MHz, CDCl 3 ) δ 8.47 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H) ), 7.03 (d, J = 8.4 Hz, 1H), 4.80 (m, 1H), 3.99 (s, 2H), 3.44 (d, J = 2.4 Hz, 2H), 2.41 (s, 3H), 2.28 (t) , J = 2.4 Hz, 1H), 1.48 (d, J = 6.4 Hz, 6H); MS.m/z 303.1, [M+H] + .

N-((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺(N6)N-((5-chloro-8-(cyclopropylmethoxy)quinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine (N6)

YD：58%.1H NMR(400MHz,CDCl3)δ8.48(d,J=8.4Hz,1H),7.77(d,J=8.8Hz,1H),7.45(d,J=8.4Hz,1H),6.98(d,J=8.4Hz,1H),4.09(d,J=7.2Hz,2H),4.01(s,2H),3.45(d,J=2.0Hz,2H),2.41(s,3H),2.28(t,J=2.0Hz,1H),1.42~1.50(m,1H),0.65-0.70(m,2H),0.42-0.45(m,2H)；MS.m/z 337.1,[M+Na]+。 YD: 58%. 1 H NMR (400MHz, CDCl 3 ) δ 8.48 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H) ), 6.98 (d, J = 8.4 Hz, 1H), 4.09 (d, J = 7.2 Hz, 2H), 4.01 (s, 2H), 3.45 (d, J = 2.0 Hz, 2H), 2.41 (s, 3H) ), 2.28 (t, J = 2.0 Hz, 1H), 1.42~1.50 (m, 1H), 0.65-0.70 (m, 2H), 0.42-0.45 (m, 2H); MS.m/z 337.1, [M +Na] + .

N-((5,7-二氯-8-甲氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺(N7)N-((5,7-Dichloro-8-methoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine (N7)

YD：58%.1H NMR(400MHz,CDCl3)δ8.47(d,J=8.8Hz,1H),7.74(d,J=8.8Hz,1H),7.60(s,1H),4.20(s,3H),3.99(s,2H),3.43(d,J=2.0Hz,2H), 2.41(s,3H),2.29(t,J=2.0Hz,1H)；MS.m/z 309.0,[M+H]+。 YD: 58%. 1 H NMR (400MHz, CDCl 3 ) δ 8.47 (d, J = 8.8 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.60 (s, 1H), 4.20 (s) , 3H), 3.99 (s, 2H), 3.43 (d, J = 2.0 Hz, 2H), 2.41 (s, 3H), 2.29 (t, J = 2.0 Hz, 1H); MS.m/z 309.0, [ M+H] + .

N-((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺(N8)N-((5,7-Dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine (N8)

YD：76%.1H NMR(400MHz,CDCl3)δ8.45(d,J=8.8Hz,1H),7.71(d,J=8.8Hz,1H),7.59(s,1H),4.25(d,J=7.6Hz,2H),3.95(s,2H),3.40(d,J=2.0Hz,2H),2.40(s,3H),2.28(t,J=2.0Hz,1H),1.41-1.45(m,1H),0.57-0.62(m,2H),0.36(dd,J=10.0,4.8Hz,2H)；MS.m/z 371.0,[M+Na]+。 YD: 76%. 1 H NMR (400MHz, CDCl 3 ) δ 8.45 (d, J = 8.8 Hz, 1H), 7.71 (d, J = 8.8 Hz, 1H), 7.59 (s, 1H), 4.25 (d) , J = 7.6 Hz, 2H), 3.95 (s, 2H), 3.40 (d, J = 2.0 Hz, 2H), 2.40 (s, 3H), 2.28 (t, J = 2.0 Hz, 1H), 1.41-1.45 (m, 1H), 0.57-0.62 (m, 2H), 0.36 (dd, J = 10.0, 4.8 Hz, 2H); MS.m/z 371.0, [M+Na] + .

8-((5-氯-8-甲氧基喹啉-2-基)甲基胺基)辛-1-醇(O1)8-((5-Chloro-8-methoxyquinolin-2-yl)methylamino) oct-1-ol (O1)

YD：44%.1H NMR(400MHz,d4-MeOD)δ8.55(d,J=8.8Hz,1H),7.69(d,J=8.8Hz,1H),7.58(d,J=8.4Hz,1H),7.16(d,J=8.4Hz,1H),4.07(s,5H),3.50(t,J=6.8Hz,2H),2.63(t,J=7.2Hz,2H),1.56(quin,J=7.2Hz,2H),1.50(quin,J=6.8Hz,2H),1.29-1.32(br,10H)；MS.m/z 351.2,[M+H]+。 YD: 44%. 1 H NMR (400MHz, d4 -MeOD) δ 8.55 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 4.07 (s, 5H), 3.50 (t, J = 6.8 Hz, 2H), 2.63 (t, J = 7.2 Hz, 2H), 1.56 (quin, J = 7.2 Hz, 2H), 1.50 (quin, J = 6.8 Hz, 2H), 1.29-1.32 (br, 10H); MS.m/z 351.2, [M+H] + .

8-((5-氯-8-乙氧基喹啉-2-基)甲基胺基)辛-1-醇(O2)8-((5-Chloro-8-ethoxyquinolin-2-yl)methylamino)octyl-1-ol (O2)

YD：41%.1H NMR(400MHz,d4-MeOD)δ8.51(d,J=8.8Hz,1H),7.66(d,J=8.4Hz,1H),7.53(d,J=8.4Hz,1H),7.12(d,J=8.4Hz,1H),4.29(q,J=6.8Hz,2H),4.07(s,2H),3.51(t,J=6.8Hz,2H),2.64(t,J=7.2Hz,2H),1.47-1.58(m,7H),1.31(br,9H)；MS.m/z 365.2,[M+H]+。 YD: 41%. 1 H NMR (400MHz, d4 -MeOD) δ 8.51 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 4.29 (q, J = 6.8 Hz, 2H), 4.07 (s, 2H), 3.51 (t, J = 6.8 Hz, 2H), 2.64 (t, J = 7.2 Hz, 2H), 1.47-1.58 (m, 7H), 1.31 (br, 9H); MS.m/z 365.2, [M+H] + .

8-((5-氯-8-異丙氧基喹啉-2-基)甲基胺基)辛-1-醇(O3)8-((5-Chloro-8-isopropoxyquinolin-2-yl)methylamino)octyl-1-ol (O3)

YD：31%.1H NMR(400MHz,d4-MeOD)δ8.55(d,J=8.8Hz,1H),7.66(d,J=8.8Hz,1H),7.56(d,J=8.4Hz,1H),7.19(d,J=8.4Hz,1H),4.89(m,1H),4.15(s,2H),3.52(t,J=6.4Hz,2H),2.71(t,J=7.2Hz,2H),1.59(quin,J=6.8Hz,2H)1.46-1.50(m,8H),1.33(br,9H)；MS.m/z 379.2,[M+H]+。 YD: 31%. 1 H NMR (400MHz, d4 -MeOD) δ 8.55 (d, J = 8.8 Hz, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.19 (d, J = 8.4 Hz, 1H), 4.89 (m, 1H), 4.15 (s, 2H), 3.52 (t, J = 6.4 Hz, 2H), 2.71 (t, J = 7.2 Hz, 2H), 1.59 (quin, J = 6.8 Hz, 2H) 1.46-1.50 (m, 8H), 1.33 (br, 9H); MS.m/z 379.2, [M+H] + .

8-((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基胺基)辛-1-醇(O4)8-((5-Chloro-8-(cyclopropylmethoxy)quinolin-2-yl)methylamino)octyl-1-ol (O4)

YD：29%.1H NMR(400MHz,d4-MeOD)δ8.54(d,J=8.4Hz,1H),7.67(d,J=8.8Hz,1H),7.54(d,J=8.4Hz,1H),7.15(d,J=8.4Hz,1H),4.09(s+d,J=6.8Hz,4H),3.51(t,J=6.8Hz,2H),2.67(t,J=7.2Hz,2H),1.59(quin,J=7.2Hz,2H),1.43-1.51(m,3H),1.29-1.42(br,10H),0.66-0.89(m,2H),0.44(dd,J =10.4,4.8Hz,2H)；MS.m/z 391.2,[M+H]+。 YD: 29%. 1 H NMR (400MHz, d4 -MeOD) δ 8.54 (d, J = 8.4 Hz, 1H), 7.67 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 4.09 (s + d, J = 6.8 Hz, 4H), 3.51 (t, J = 6.8 Hz, 2H), 2.67 (t, J = 7.2 Hz, 2H), 1.59 (quin, J = 7.2 Hz, 2H), 1.43-1.51 (m, 3H), 1.29-1.42 (br, 10H), 0.66-0.89 (m, 2H), 0.44 (dd, J = 10.4, 4.8 Hz, 2H); MS.m/z 391.2, [M+H] + .

8-((5,7-二氯-8-甲氧基喹啉-2-基)甲基胺基)辛-1-醇(O5)8-((5,7-Dichloro-8-methoxyquinolin-2-yl)methylamino)octyl-1-ol (O5)

YD：37%.1H NMR(400MHz,d4-MeOD)δ8.54(d,J=8.8Hz,1H),7.71(s,1H),7.65(d,J=8.8Hz,1H),4.14(s,3H),4.12(s,2H),3.52(t,J=6.8Hz,2H),2.70(t,J=7.2Hz,2H),1.60(quin,J=6.8Hz,2H),1.50(m,2H),1.33(br,9H)；MS.m/z 385.1,[M+H]+。 YD: 37%. 1 H NMR (400MHz, d4 -MeOD) δ 8.54 (d, J = 8.8 Hz, 1H), 7.71 (s, 1H), 7.65 (d, J = 8.8 Hz, 1H), 4.14 ( s, 3H), 4.12 (s, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.70 (t, J = 7.2 Hz, 2H), 1.60 (quin, J = 6.8 Hz, 2H), 1.50 ( m, 2H), 1.33 (br, 9H); MS.m/z 385.1, [M+H] + .

8-((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基胺基)辛-1-醇(O6)8-((5,7-Dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)methylamino)octyl-1-ol (O6)

YD：56%.1H NMR(400MHz,d4-MeOD)δ8.51(d,J=8.4Hz,1H),7.69(s,1H),7.61(d,J=8.8Hz,1H),4.22(d,J=7.2Hz,2H),4.10(s,2H),3.52(t,J=6.8Hz,2H),2.68(t,J=7.2Hz,2H),1.59(quin,J=7.2Hz,2H),1.51(quin,J=6.8Hz,2H),1.28-1.42(br,11H),0.55-0.60(m,2H),0.30-0.33(m,2H)；MS.m/z 425.2,[M+H]+。 YD: 56%. 1 H NMR (400MHz, d4 -MeOD) δ 8.51 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.61 (d, J = 8.8 Hz, 1H), 4.22 ( d, J = 7.2 Hz, 2H), 4.10 (s, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.68 (t, J = 7.2 Hz, 2H), 1.59 (quin, J = 7.2 Hz, 2H), 1.51 (quin, J = 6.8 Hz, 2H), 1.28-1.42 (br, 11H), 0.55-0.60 (m, 2H), 0.30-0.33 (m, 2H); MS.m/z 425.2, [ M+H] + .

6-(雙((8-甲氧基喹啉-2-基)甲基)胺基)己-1-醇(P1)6-(bis((8-methoxyquinolin-2-yl)methyl)amino)hexan-1-ol (P1)

1H NMR(400MHz,d4-MeOD)δ8.18(d,J=8.4Hz,2H),7.80(d,J=8.4Hz,2H),7.44(t,J=8.0Hz,2H),7.38(d,J=8.0Hz,2H),7.13(d,J=7.2Hz,2H),4.02(s,6H),3.99(s,4H),3.40(t,J=6.8Hz,2H),2.59(t,J=6.8Hz,2H),1.56(quin,J=6.8Hz,2H),1.41(quin,J=6.8Hz,2H),1.27(quin,J=7.6Hz,2H),1.18(quin,J=6.8Hz,2H)；MS.m/z 482.3,[M+Na]+。 1 H NMR (400MHz, d4 -MeOD ) δ8.18 (d, J = 8.4Hz, 2H), 7.80 (d, J = 8.4Hz, 2H), 7.44 (t, J = 8.0Hz, 2H), 7.38 ( d, J = 8.0 Hz, 2H), 7.13 (d, J = 7.2 Hz, 2H), 4.02 (s, 6H), 3.99 (s, 4H), 3.40 (t, J = 6.8 Hz, 2H), 2.59 ( t, J = 6.8 Hz, 2H), 1.56 (quin, J = 6.8 Hz, 2H), 1.41 (quin, J = 6.8 Hz, 2H), 1.27 (quin, J = 7.6 Hz, 2H), 1.18 (quin, J = 6.8 Hz, 2H); MS.m/z 482.3, [M+Na] + .

圖1A顯示利用剛果紅染色後，C12於鋅離子存在或不存在條件下抑制Aβ凝集之顯微分析。圖1B及圖2顯示C12溶解已進行的Aβ凝集。圖3A-B顯示化合物C12、CQ及C12中間體保護神經元細胞免受鋅誘發的fAβ。只有化合物C12對不含鋅的凝集有效(圖3B)。圖4顯示化合物B3、C3及D3分別於未分化PC12細胞上引發的軸突生長誘發現象。圖5顯示喹啉衍生物增加GAP43之表現。圖6顯示化合物C12與B3對於fAβ誘發之 記憶障礙小鼠可改善學習表現。C12與B3(10mg/kg)增加fAβ病變小鼠於滾輪試驗中之運動時間。圖7A-D顯示化合物C12於Morris水迷宮試驗中改善記憶障礙之fAβ病變小鼠的學習。針對小鼠，評估其爬上隱藏平台的總移動期間(圖7A)及總移動距離(圖7B)；並量化其出現在目標區域的百分比(圖7C)，表示其進入隱藏平台周圍的區域之相對時間(相較於游泳的總時間)；並評估平均游泳速度(圖7D)以鑑別由運動元活性改善所造成的記憶改善。圖8顯示於化合物C12在記憶障礙fAβ病變小鼠中造成GAP43增加及fAβ減少。 Figure 1A shows microscopic analysis of inhibition of A[beta] agglutination by C12 in the presence or absence of zinc ions after staining with Congo red. Figure 1B and Figure 2 show that A12 agglutination has been carried out by C12 dissolution. 3A-B show that compounds C12, CQ and C12 intermediates protect neuronal cells from zinc-induced fAβ. Only compound C12 was effective for zinc-free agglutination (Fig. 3B). Figure 4 shows the phenomenon of axonal growth induced by compounds B3, C3 and D3 on undifferentiated PC12 cells, respectively. Figure 5 shows that quinoline derivatives increase the performance of GAP43. Figure 6 shows that compounds C12 and B3 are induced for fAβ Memory impairment mice can improve learning performance. C12 and B3 (10 mg/kg) increased the exercise time of fAβ-lesioned mice in the roller test. Figures 7A-D show the learning of fAβ-lesioned mice with compound C12 in improving memory impairment in the Morris water maze test. For the mouse, evaluate the total movement period (Fig. 7A) and total movement distance (Fig. 7B) of the hidden platform; and quantify the percentage of its appearance in the target area (Fig. 7C), indicating that it enters the area around the hidden platform. Relative time (compared to the total time of swimming); and average swimming speed (Fig. 7D) was assessed to identify memory improvements caused by improved motoneuron activity. Figure 8 shows that compound C12 causes an increase in GAP43 and a decrease in fAβ in mice with memory disorder fAβ lesions.

前述關於本發明例示性實施例之描述僅是為了說明及描述之目的，且並不欲用於完整列舉或將本發明限制於所清楚揭示之態樣。參照前述教示後，將可有各種變化及修飾。 The foregoing description of the preferred embodiments of the invention are intended to Various changes and modifications are possible in light of the above teachings.

前述實施例及實例之選擇及描述是為了解釋本發明的原理及其實際應用，以使本領域具有通常知識者能利用本發明及各種實施例，並加以進行各種修飾以符合特定之用途。在不脫離本發明之精神與範圍的前提下，本發明所屬技術領域中具有通常知識者可輕易思及其他實施例。因此，本發明之範圍應由隨附申請專利範圍所決定，而非由本文所述之例示性實施例及前述說明所決定。 The foregoing embodiments and examples have been chosen and described in order to explain the embodiments of the invention Other embodiments may be readily apparent to those of ordinary skill in the art without departing from the scope of the invention. Therefore, the scope of the invention should be determined by the scope of the appended claims, and not by the exemplary embodiments described herein and the foregoing description.

可包括專利、專利申請案及其他公開文獻的參考文獻乃於本發明之說明中予以引用及討論。參考文獻的此等引用及討論僅僅是為了闡明本發明之描述，且並不代表申請人承認此等參考文獻為本發明之先前技術。於本說明書中所引用及討論的所有參考文獻均就其所有內容併入本文作為參考，且併入參考之範圍等同於此等參考文獻係各別併入本文作為參考。 References that may include patents, patent applications, and other publications are cited and discussed in the description of the present invention. The citation and discussion of the references are merely illustrative of the invention and are not intended to be an admission All of the references cited and discussed in this specification are hereby incorporated by reference in its entirety in its entirety in its entirety in its entirety in the extent of the disclosure of the disclosure.

Claims (15)

一種式(I)化合物或其醫藥可接受性鹽類： 其中R1為氫、(C1-C8)烷基、(C1-C8)伸烷基(C3-C8)環烷基、(C1-C8)鹵烷基或(C1-C8)伸烷基(C6-C20)芳基；R2為氫或鹵素；R3為氫、鹵素、(C1-C8)烷基或(C1-C8)烷氧基；R4為氫、鹵素、(C1-C8)烷基、(C1-C8)烷氧基或(C1-C8)鹵烷基；R5為氫或(C1-C20)烷醇；R6為氫；且R7為氫、(C5-C20)烷醇、(C1-C8)伸烷基(C3-C8)雜環基(C1-C20)烷醇、(C1-C8)伸烷基(C3-C8)雜環基(C1-C20)烷基、(C10-C13)伸烷基OCOCH3、(C1-C8)伸烷基(C1-C6)烷基胺基(C1-C6)炔基或(C1-C8)伸烷基胺基(C1-C20)烷醇；其中，R5及R7不同時為氫；以及其中，當R7為氫時，R5為(C5-C20)烷醇。 A compound of formula (I) or a pharmaceutically acceptable salt thereof: Wherein R 1 is hydrogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkyl (C 3 -C 8 )cycloalkyl, (C 1 -C 8 )haloalkyl or (C) 1 -C 8 )alkyl (C 6 -C 20 ) aryl; R 2 is hydrogen or halogen; R 3 is hydrogen, halogen, (C 1 -C 8 )alkyl or (C 1 -C 8 ) alkane Alkyl; R 4 is hydrogen, halogen, (C 1 -C 8 )alkyl, (C 1 -C 8 )alkoxy or (C 1 -C 8 )haloalkyl; R 5 is hydrogen or (C 1 -C 20 ) an alkanol; R 6 is hydrogen; and R 7 is hydrogen, (C 5 -C 20 ) alkanol, (C 1 -C 8 )alkyl (C 3 -C 8 )heterocyclyl (C) 1 -C 20 ) alkanol, (C 1 -C 8 )alkyl (C 3 -C 8 )heterocyclyl (C 1 -C 20 )alkyl, (C 10 -C 13 )alkylene OCOCH 3 (C 1 -C 8 )alkyl (C 1 -C 6 )alkylamino (C 1 -C 6 ) alkynyl or (C 1 -C 8 )alkylamino (C 1 -C 20 An alkanol; wherein R 5 and R 7 are not simultaneously hydrogen; and wherein, when R 7 is hydrogen, R 5 is a (C 5 -C 20 ) alkanol. 如請求項1所述之化合物或其醫藥可接受性鹽類，其中 R1為氫、CH3、CH2CH3、CH(CH3)2、CH2CH(CH3)2、CH2CH(CH2)2、CF3或苯甲基；R2為氫、F或Cl；R3為氫、F、Cl、CH3或OCH3；R4為氫、F、Cl、Br、CH3、OCH3或CF3；R5為氫、(CH2)11OH或(CH2)12OH；R6為氫；且R7為氫、(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH、(CH2)14OH、(CH2)15OH、(CH2)10OCOCH3、(CH2)11OCOCH3、(CH2)12OCOCH3、(CH2)13OCOCH3、CH2(N(CH2CH2)2N)CH2CH2OH、CH2(N(CH2CH2)2N)CH2CH3、CH2N(CH3)CH2C≡CH或CH2NH(CH2)8OH；其中，R5及R7不同時為氫。 The compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , CH 2 CH (CH 2 ) 2 , CF 3 or benzyl; R 2 is hydrogen, F or Cl; R 3 is hydrogen, F, Cl, CH 3 or OCH 3 ; R 4 is hydrogen, F, Cl, Br, CH 3 , OCH 3 or CF 3 ; R 5 is hydrogen, (CH 2 ) 11 OH or (CH 2 ) 12 OH; R 6 is hydrogen; and R 7 is hydrogen, (CH 2 ) 9 OH, (CH 2 ) 10 OH , (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH, (CH 2 ) 14 OH, (CH 2 ) 15 OH, (CH 2 ) 10 OCOCH 3 , (CH 2 ) 11 OCOCH 3 , (CH 2 ) 12 OCOCH 3 , (CH 2 ) 13 OCOCH 3 , CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 2 OH, CH 2 (N(CH 2 CH 2 ) 2 N) CH 2 CH 3 , CH 2 N(CH 3 )CH 2 C≡CH or CH 2 NH(CH 2 ) 8 OH; wherein R 5 and R 7 are not hydrogen at the same time. 如請求項2所述之化合物或其醫藥可接受性鹽類，其中R1為氫、CH3、CH2CH3、CH(CH3)2、CH2CH(CH3)2、CH2CH(CH2)2、CF3或苯甲基；R2、R3、R4、R5及R6係各自獨立為氫；且R7為(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH、(CH2)14OH、(CH2)15OH、CH2(N(CH2CH2)2N)CH2CH2OH或CH2N(CH3)CH2C≡CH。 The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 , CH 2 CH (CH 2 ) 2 , CF 3 or benzyl; R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; and R 7 is (CH 2 ) 9 OH, (CH 2 ) 10 OH , (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH, (CH 2 ) 14 OH, (CH 2 ) 15 OH, CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 2 OH or CH 2 N(CH 3 )CH 2 C≡CH. 如請求項2所述之化合物或其醫藥可接受性鹽類，其中 R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2或CH(CH3)2；R2、R3、R5及R6係各自獨立為氫；R4為CH3、F、Cl、Br、CF3或OCH3；且R7為(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH、(CH2)15OH、(CH2)10OCOCH3、(CH2)11OCOCH3、(CH2)12OCOCH3、(CH2)13OCOCH3、CH2NH(CH2)8OH、CH2(N(CH2CH2)2N)CH2CH2OH、CH2(N(CH2CH2)2N)CH2CH3或CH2N(CH3)CH2C≡CH。 The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 or CH (CH 3 ) 2 ; R 2 , R 3 , R 5 and R 6 are each independently hydrogen; R 4 is CH 3 , F, Cl, Br, CF 3 or OCH 3 ; and R 7 is (CH 2 ) 9 OH, (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH, (CH 2 ) 15 OH, (CH 2 ) 10 OCOCH 3 , (CH 2 ) 11 OCOCH 3 , (CH 2 ) 12 OCOCH 3 , (CH 2 ) 13 OCOCH 3 , CH 2 NH(CH 2 ) 8 OH, CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 2 OH, CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 3 or CH 2 N(CH 3 )CH 2 C≡CH. 如請求項2所述之化合物或其醫藥可接受性鹽類，其中R1為氫、CH3、CH2CH3、CH(CH2)2或CH2CH(CH2)2；R2、R4係各自獨立為Cl；R3、R5及R6係各自獨立為氫；且R7為(CH2)11OH、CH2NH(CH2)8OH或CH2N(CH3)CH2C≡CH。 The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH(CH 2 ) 2 or CH 2 CH(CH 2 ) 2 ; R 2 , R 4 is each independently Cl; R 3 , R 5 and R 6 are each independently hydrogen; and R 7 is (CH 2 ) 11 OH, CH 2 NH(CH 2 ) 8 OH or CH 2 N(CH 3 ) CH 2 C≡CH. 如請求項2所述之化合物或其醫藥可接受性鹽類，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2、CH(CH3)2或苯甲基；R2、R3、R4、R6及R7係各自獨立為氫；且R5為(CH2)11OH或(CH2)12OH。 The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 , CH (CH 3 ) 2 or benzyl; R 2 , R 3 , R 4 , R 6 and R 7 are each independently hydrogen; and R 5 is (CH 2 ) 11 OH or (CH 2 ) 12 OH. 如請求項2所述之化合物或其醫藥可接受性鹽類，其中R1為CH3；R2、R5及R6係各自獨立為氫；R3及R4係各自獨立為OCH3或Cl；且 R7為(CH2)11OH。 The compound of claim 2, or a pharmaceutically acceptable salt thereof, wherein R 1 is CH 3 ; R 2 , R 5 and R 6 are each independently hydrogen; and R 3 and R 4 are each independently OCH 3 or Cl; and R 7 is (CH 2 ) 11 OH. 如請求項2所述之化合物或其醫藥可接受性鹽類，其係選自下列所組成之群組：9-(8-(苯甲氧基)喹啉-2-基)壬-1-醇、10-(8-(苯甲氧基)喹啉-2-基)癸-1-醇、11-(8-(苯甲氧基)喹啉-2-基)十一-1-醇、12-(8-(苯甲氧基)喹啉-2-基)十二-1-醇、13-(8-(苯甲氧基)喹啉-2-基)十三-1-醇、14-((8-(苯甲氧基)喹啉-2-基)十四-1-醇、15-(8-(苯甲氧基)喹啉-2-基)十五-1-醇、11-(8-(苯甲氧基)-5-甲基喹啉-2-基)十一-1-醇、11-(8-(苯甲氧基)-6-甲基喹啉-2-基)十一-1-醇、11-(8-(苯甲氧基)-5-氟喹啉-2-基)十一-1-醇、11-(8-(苯甲氧基)-5-氯喹啉-2-基)十一-1-醇、2-(9-羥壬基)喹啉-8-醇、2-(10-羥癸基)喹啉-8-醇、2-(11-羥十一基)喹啉-8-醇、2-(12-羥十二基)喹啉-8-醇、2-(13-羥十三基)喹啉-8-醇、2-(14-羥十四基)喹啉-8-醇、2-(15-羥十五基)喹啉-8-醇、2-(11-羥十一基)-5-甲基喹啉-8-醇、 2-(11-羥十一基)-6-甲基喹啉-8-醇、5-氯-2-(11-羥十一基)喹啉-8-醇、9-(8-甲氧基喹啉-2-基)壬-1-醇、10-(8-甲氧基喹啉-2-基)癸-1-醇、11-(8-甲氧基喹啉-2-基)十一-1-醇、12-(8-甲氧基喹啉-2-基)十二-1-醇、13-(8-甲氧基喹啉-2-基)十三-1-醇、14-((8-甲氧基喹啉-2-基)十四-1-醇、15-(8-甲氧基喹啉-2-基)十五-1-醇、11-(8-甲氧基-5-甲基喹啉-2-基)十一-1-醇、11-(5-氟-8-甲氧基喹啉-2-基)十一-1-醇、12-(5-氟-8-甲氧基喹啉-2-基)十二-1-醇、9-(5-氯-8-甲氧基喹啉-2-基)壬-1-醇、11-(5-氯-8-甲氧基喹啉-2-基)十一-1-醇、15-(5-氯-8-甲氧基喹啉-2-基)十五-1-醇、11-(5-溴-8-甲氧基喹啉-2-基)十一-1-醇、11-(8-甲氧基-5-(三氟甲基)喹啉-2-基)十一-1-醇、11-(5,8-二甲氧基喹啉-2-基)十一-1-醇、11-(8-甲氧基-6-甲基喹啉-2-基)十一-1-醇、11-(6-氟-8-甲氧基喹啉-2-基)十一-1-醇、11-(6-氯-8-甲氧基喹啉-2-基)十一-1-醇、11-(7-氟-8-甲氧基喹啉-2-基)十一-1-醇、 11-(7-氯-8-甲氧基喹啉-2-基)十一-1-醇、11-(5-氯-6,8-二甲氧基喹啉-2-基)十一-1-醇、11-(6-氯-5,8-二甲氧基喹啉-2-基)十一-1-醇、11-(5,7-二氯-8-甲氧基喹啉-2-基)十一-1-醇、9-(8-乙氧基喹啉-2-基)壬-1-醇、10-(8-乙氧基喹啉-2-基)癸-1-醇、11-(8-乙氧基喹啉-2-基)十一-1-醇、12-(8-乙氧基喹啉-2-基)十二-1-醇、13-(8-乙氧基喹啉-2-基)十三-1-醇、14-((8-乙氧基喹啉-2-基)十四-1-醇、15-(8-乙氧基喹啉-2-基)十五-1-醇、11-(8-乙氧基-5-甲基喹啉-2-基)十一-1-醇、11-(8-乙氧基-5-氟喹啉-2-基)十一-1-醇、9-(5-氯-8-乙氧基喹啉-2-基)壬-1-醇、11-(5-氯-8-乙氧基喹啉-2-基)十一-1-醇、15-(5-氯-8-乙氧基喹啉-2-基)十五-1-醇、11-(5-溴-8-乙氧基喹啉-2-基)十一-1-醇、11-(5,7-二氯-8-乙氧基喹啉-2-基)十一-1-醇、9-(8-異丙氧基喹啉-2-基)壬-1-醇、10-(8-異丙氧基喹啉-2-基)癸-1-醇、11-(8-異丙氧基喹啉-2-基)十一-1-醇、12-(8-異丙氧基喹啉-2-基)十二-1-醇、 13-(8-異丙氧基喹啉-2-基)十三-1-醇、14-((8-異丙氧基喹啉-2-基)十四-1-醇、15-(8-異丙氧基喹啉-2-基)十五-1-醇、11-(8-異丙氧基-5-甲基喹啉-2-基)十一-1-醇、11-(5-氟-8-異丙氧基喹啉-2-基)十一-1-醇、9-(5-氯-8-異丙氧基喹啉-2-基)壬-1-醇、11-(5-氯-8-異丙氧基喹啉-2-基)十一-1-醇、15-(5-氯-8-異丙氧基喹啉-2-基)十五-1-醇、11-(5-溴-8-異丙氧基喹啉-2-基)十一-1-醇、11-(5,7-二氯-8-異丙氧基喹啉-2-基)十一-1-醇、9-(8-(環丙基甲氧基)喹啉-2-基)壬-1-醇、10-(8-(環丙基甲氧基)喹啉-2-基)癸-1-醇、11-(8-(環丙基甲氧基)喹啉-2-基)十一-1-醇、12-(8-(環丙基甲氧基)喹啉-2-基)十二-1-醇、13-(8-(環丙基甲氧基)喹啉-2-基)十三-1-醇、14-((8-(環丙基甲氧基)喹啉-2-基)十四-1-醇、15-(8-(環丙基甲氧基)喹啉-2-基)十五-1-醇、11-(8-(環丙基甲氧基)-5-甲基喹啉-2-基)十一-1-醇、11-(8-(環丙基甲氧基)-5-氟喹啉-2-基)十一-1-醇、9-(5-氯-8-(環丙基甲氧基)喹啉-2-基)壬-1-醇、11-(5-氯-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇、15-(5-氯-8-(環丙基甲氧基)喹啉-2-基)十五-1-醇、 11-(5-溴-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇、11-(5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)十一-1-醇、5,7-二氯-2-(11-羥十一基)喹啉-8-醇、10-(5-氯-8-甲氧基喹啉-2-基)癸-1-醇、乙酸10-(5-氯-8-甲氧基喹啉-2-基)癸酯、11-(5-氯-8-甲氧基喹啉-2-基)十一-1-醇、乙酸11-(5-氯-8-甲氧基喹啉-2-基)十一酯、12-(5-氯-8-甲氧基喹啉-2-基)十二-1-醇、乙酸12-(5-氯-8-甲氧基喹啉-2-基)十二酯、13-(5-氯-8-甲氧基喹啉-2-基)十三-1-醇、乙酸13-(5-氯-8-甲氧基喹啉-2-基)十三酯、11-(8-甲氧基喹啉-4-(-基)十一-1-醇、11-(8-乙氧基喹啉-4-(-基)十一-1-醇、11-(8-異丙氧基喹啉-4-(-基)十一-1-醇、11-(8-(環丙基甲氧基)喹啉-4-(-基)十一-1-醇、11-(8-(苯甲氧基)喹啉-4-(-基)十一-1-醇、12-(8-(苯甲氧基)喹啉-4-(-基)十二-1-醇、4-((11-羥十一基)喹啉-8-醇、4-((12-羥十二基)喹啉-8-醇、9-(8-(三氟甲氧基)喹啉-2-基)壬-1-醇、11-(8-(三氟甲氧基)喹啉-2-基)十一-1-醇、14-((8-(三氟甲氧基)喹啉-2-基)十四-1-醇、 15-(8-(三氟甲氧基)喹啉-2-基)十五-1-醇、2-((4-((2-羥乙基)哌【口+井】-1-基)甲基)喹啉-8-醇、2-(4-(((5-氯-8-甲氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-(4-(((5-氯-8-乙氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-(4-(((5-氯-8-異丙氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-(4-(((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基)哌【口+井】-1-基)乙烷、2-(4-(((5,7-二氯-8-甲氧基喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-(4-(((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基)哌【口+井】-1-基)乙醇、2-((甲基(丙-2-炔基)胺基)甲基)喹啉-8-醇、5-氯-2-((甲基(丙-2-炔基)胺基)甲基)喹啉-8-醇、N((5-氯-8-甲氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5-氯-8-乙氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5-氯-8-異丙氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5,7-二氯-8-甲氧基喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、N((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基)-N-甲基丙-2-炔-1-胺、8-((5-氯-8-甲氧基喹啉-2-基)甲基胺基)辛-1-醇、8-((5-氯-8-乙氧基喹啉-2-基)甲基胺基)辛-1-醇、8-((5-氯-8-異丙氧基喹啉-2-基)甲基胺基)辛-1-醇、8-((5-氯-8-(環丙基甲氧基)喹啉-2-基)甲基胺基)辛-1-醇、8-((5,7-二氯-8-甲氧基喹啉-2-基)甲基胺基)辛-1-醇以及 8-((5,7-二氯-8-(環丙基甲氧基)喹啉-2-基)甲基胺基)辛-1-醇。 The compound of claim 2, or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of 9-(8-(benzyloxy)quinolin-2-yl)indole-1- Alcohol, 10-(8-(benzyloxy)quinolin-2-yl)indol-1-ol, 11-(8-(benzyloxy)quinolin-2-yl)undec-1-ol , 12-(8-(benzyloxy)quinolin-2-yl)dodec-1-ol, 13-(8-(benzyloxy)quinolin-2-yl)tridec-1-ol ,14-((8-(Benzyloxy)quinolin-2-yl)tetradec-1-ol, 15-(8-(benzyloxy)quinolin-2-yl)penta-1- Alcohol, 11-(8-(benzyloxy)-5-methylquinolin-2-yl)undec-1-ol, 11-(8-(benzyloxy)-6-methylquinoline -2-yl)undec-1-ol, 11-(8-(benzyloxy)-5-fluoroquinolin-2-yl)undec-1-ol, 11-(8-(benzyloxy) 5-(chloroquinolin-2-yl)undec-1-ol, 2-(9-hydroxyindolyl)quinolin-8-ol, 2-(10-hydroxyindenyl)quinoline-8-ol , 2-(11-hydroxyundecyl)quinolin-8-ol, 2-(12-hydroxydodecyl)quinolin-8-ol, 2-(13-hydroxytridecyl)quinoline-8- Alcohol, 2-(14-hydroxytetradecyl)quinolin-8-ol, 2-(15-hydroxypentadecyl)quinolin-8-ol, 2-(11-hydroxyundecyl)-5-A Quinoquinoline-8-ol, 2-(11-Hydroxyundecyl)-6-methylquinolin-8-ol, 5-chloro-2-(11-hydroxyundecyl)quinolin-8-ol, 9-(8-methoxy Quinolin-2-yl)nonanol, 10-(8-methoxyquinolin-2-yl)indol-1-ol, 11-(8-methoxyquinolin-2-yl) Undec-1-ol, 12-(8-methoxyquinolin-2-yl)dodec-1-ol, 13-(8-methoxyquinolin-2-yl)tridec-1-ol , 14-((8-methoxyquinolin-2-yl)tetradec-1-ol, 15-(8-methoxyquinolin-2-yl)pentadecan-1-ol, 11-(8 -Methoxy-5-methylquinolin-2-yl)undec-1-ol, 11-(5-fluoro-8-methoxyquinolin-2-yl)undec-1-ol, 12 -(5-fluoro-8-methoxyquinolin-2-yl)dodec-1-ol, 9-(5-chloro-8-methoxyquinolin-2-yl)indol-1-ol, 11-(5-chloro-8-methoxyquinolin-2-yl)undec-1-ol, 15-(5-chloro-8-methoxyquinolin-2-yl)penta-1- Alcohol, 11-(5-bromo-8-methoxyquinolin-2-yl)undec-1-ol, 11-(8-methoxy-5-(trifluoromethyl)quinolin-2- Ethyl-1-decanol, 11-(5,8-dimethoxyquinolin-2-yl)undec-1-ol, 11-(8-methoxy-6-methylquinoline- 2-yl)undec-1-ol, 11-(6-fluoro-8-methoxyquinolin-2-yl)undec-1-ol, 11-(6-chloro-8-methoxyquin Benzan-2-yl)undec-1-ol, 11-(7-fluoro-8-methoxy 2-yl) undec-1-ol, 11-(7-chloro-8-methoxyquinolin-2-yl)undec-1-ol, 11-(5-chloro-6,8-dimethoxyquinolin-2-yl) eleven 1-ol, 11-(6-chloro-5,8-dimethoxyquinolin-2-yl)undec-1-ol, 11-(5,7-dichloro-8-methoxyquin Benz-2-yl)undec-1-ol, 9-(8-ethoxyquinolin-2-yl)indol-1-ol, 10-(8-ethoxyquinolin-2-yl)anthracene 1-ol, 11-(8-ethoxyquinolin-2-yl)undec-1-ol, 12-(8-ethoxyquinolin-2-yl)dodec-1-ol, 13 -(8-ethoxyquinolin-2-yl)tridec-1-ol, 14-((8-ethoxyquinolin-2-yl)tetradec-1-ol, 15-(8-B Oxyquinolin-2-yl)pentadecan-1-ol, 11-(8-ethoxy-5-methylquinolin-2-yl)undec-1-ol, 11-(8-ethoxy 5--5-fluoroquinolin-2-yl)undec-1-ol, 9-(5-chloro-8-ethoxyquinolin-2-yl)indol-1-ol, 11-(5-chloro -8-ethoxyquinolin-2-yl)undec-1-ol, 15-(5-chloro-8-ethoxyquinolin-2-yl)pentadecan-1-ol, 11-(5 -Bromo-8-ethoxyquinolin-2-yl)undec-1-ol, 11-(5,7-dichloro-8-ethoxyquinolin-2-yl)undec-1-ol , 9-(8-isopropoxyquinolin-2-yl)indol-1-ol, 10-(8-isopropoxyquinolin-2-yl)indol-1-ol, 11-(8- Isopropoxyquinolin-2-yl)undec-1-ol, 12-(8-isopropoxy Quinolin-2-yl) dodecanoyl-1-ol, 13-(8-isopropoxyquinolin-2-yl)tridec-1-ol, 14-((8-isopropoxyquinolin-2-yl)tetradecyl alcohol, 15-( 8-isopropoxyquinolin-2-yl)pentadecan-1-ol, 11-(8-isopropoxy-5-methylquinolin-2-yl)undec-1-ol, 11- (5-Fluoro-8-isopropoxyquinolin-2-yl)undec-1-ol, 9-(5-chloro-8-isopropoxyquinolin-2-yl)indol-1-ol , 11-(5-chloro-8-isopropoxyquinolin-2-yl)undec-1-ol, 15-(5-chloro-8-isopropoxyquinolin-2-yl) fifteen 1-ol, 11-(5-bromo-8-isopropoxyquinolin-2-yl)undec-1-ol, 11-(5,7-dichloro-8-isopropoxyquinoline -2-yl)undec-1-ol, 9-(8-(cyclopropylmethoxy)quinolin-2-yl)indol-1-ol, 10-(8-(cyclopropylmethoxy) Quinolin-2-yl)indol-1-ol, 11-(8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol, 12-(8-(cyclopropyl) Methoxy)quinolin-2-yl)dodec-1-ol, 13-(8-(cyclopropylmethoxy)quinolin-2-yl)tridec-1-ol, 14-(8 -(cyclopropylmethoxy)quinolin-2-yl)tetradec-1-ol, 15-(8-(cyclopropylmethoxy)quinolin-2-yl)pentadecan-1-ol, 11-(8-(cyclopropylmethoxy)-5-methylquinolin-2-yl)undec-1-ol, 11-(8-(cyclopropylmethoxy)-5-fluoroquin Phenan-2-yl)undec-1-ol 9-(5-chloro-8-(cyclopropylmethoxy)quinolin-2-yl)indol-1-ol, 11-(5-chloro-8-(cyclopropylmethoxy)quinoline- 2-yl)undec-1-ol, 15-(5-chloro-8-(cyclopropylmethoxy)quinolin-2-yl)pentadecan-1-ol, 11-(5-Bromo-8-(cyclopropylmethoxy)quinolin-2-yl)undec-1-ol, 11-(5,7-dichloro-8-(cyclopropylmethoxy) Quinoline-2-yl)undec-1-ol, 5,7-dichloro-2-(11-hydroxyundecyl)quinolin-8-ol, 10-(5-chloro-8-methoxy Quinolin-2-yl)indol-1-ol, 10-(5-chloro-8-methoxyquinolin-2-yl)nonanyl acetate, 11-(5-chloro-8-methoxyquin Oxalin-2-yl)undec-1-ol, 11-(5-chloro-8-methoxyquinolin-2-yl)undecyl acetate, 12-(5-chloro-8-methoxyquin Oxa-2-yl)dodec-1-ol, 12-(5-chloro-8-methoxyquinolin-2-yl)dodecyl acetate, 13-(5-chloro-8-methoxyquin Benzan-2-yl)tridec-1-ol, 13-(5-chloro-8-methoxyquinolin-2-yl)tridecyl acetate, 11-(8-methoxyquinolin-4- (-yl)undec-1-ol, 11-(8-ethoxyquinolin-4-(-yl)undec-1-ol, 11-(8-isopropoxyquinolin-4-() -yl)undec-1-ol, 11-(8-(cyclopropylmethoxy)quinolin-4-(-yl)undec-1-ol, 11-(8-(benzyloxy) Quinoline-4-(-yl)undec-1-ol, 12-(8-(benzyloxy)quinolin-4-(-yl)dodec-1-ol, 4-((11-hydroxyl) Eleven)quinolin-8-ol, 4-((12-hydroxydodecyl)quinolin-8-ol, 9-(8-(trifluoromethoxy)quinolin-2-yl)anthracene- 1-ol, 11-(8-(trifluoromethoxy) ) Quinolin-2-yl) undec-1-ol 14 - ((8- (trifluoromethoxy) quinolin-2-yl) Fourteen-1-ol, 15-(8-(Trifluoromethoxy)quinolin-2-yl)pentadecan-1-ol, 2-((4-((2-hydroxyethyl))pipeper] )methyl)quinoline-8-ol, 2-(4-((5-chloro-8-methoxyquinolin-2-yl)methyl)pipepoxide [mouth + well]-1-yl)ethanol , 2-(4-((5-Chloro-8-ethoxyquinolin-2-yl)methyl)piperidone [mouth + well]-1-yl)ethanol, 2-(4-(((5) -Chloro-8-isopropoxyquinolin-2-yl)methyl)piper [mouth + well]-1-yl)ethanol, 2-(4-((5-chloro-8-)cyclopropyl) Methoxy)quinolin-2-yl)methyl)piper [mouth + well]-1-yl)ethane, 2-(4-((5,7-dichloro-8-methoxyquinoline) -2-yl)methyl)piper [mouth + well]-1-yl)ethanol, 2-(4-((5,7-dichloro-8-(cyclopropylmethoxy))quinoline-2 -yl)methyl)piper [mouth + well]-1-yl)ethanol, 2-((methyl(prop-2-ynyl)amino)methyl)quinolin-8-ol, 5-chloro- 2-((Methyl(prop-2-ynyl)amino)methyl)quinolin-8-ol, N((5-chloro-8-methoxyquinolin-2-yl)methyl)- N-methylprop-2-yn-1-amine, N((5-chloro-8-ethoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine , N((5-chloro-8-isopropoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine, N((5-chloro-8-(cyclo) Propylmethoxy)quinolin-2-yl)methyl)-N-methylpropan-2-yne-1 -amine, N((5,7-dichloro-8-methoxyquinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine, N((5,7- Dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)methyl)-N-methylprop-2-yn-1-amine, 8-((5-chloro-8-methoxy) Quinolin-2-yl)methylamino)oct-1-ol, 8-((5-chloro-8-ethoxyquinolin-2-yl)methylamino)octyl-1-ol, 8-((5-Chloro-8-isopropoxyquinolin-2-yl)methylamino)octyl-1-ol, 8-((5-chloro-8-(cyclopropylmethoxy)) Quinoline-2-yl)methylamino)octyl-1-ol, 8-((5,7-dichloro-8-methoxyquinolin-2-yl)methylamino)oct-1- Alcohol and 8-((5,7-Dichloro-8-(cyclopropylmethoxy)quinolin-2-yl)methylamino)oct-1-ol. 一種製備請求項1所述化合物或其醫藥可接受性鹽類之方法，包括：(1)將式(II)化合物 其中：R2、R3、R4、R5及R6係各自獨立為氫；或R2、R4、R5及R6係各自獨立為氫且R3為CH3；或R2、R3、R5及R6係各自獨立為氫且R4為CH3、F、Cl或Br；或R2、R5、R6係各自獨立為氫、R3為OCH3且R4為Cl；或R2、R4為Cl且R3、R5、R6係各自獨立為氫，與溴甲苯、碘甲烷、碘乙烷、2-溴丙烷或亞甲基環丙基溴於一鹼性溶液中於約室溫至約80℃下進行反應，以獲得式(III)化合物 其中：R1為CH3、CH2CH3、CH(CH3)2、CH2CH(CH3)2或苯甲基；且 R2、R3、R4、R5及R6係各自獨立為氫；或R2、R4、R5及R6係各自獨立為氫且R3為CH3；或R2、R3、R5及R6係各自獨立為氫且R4為CH3、F、Cl或Br；或R2、R5、R6係各自獨立為氫、R3為OCH3且R4為Cl；或R2、R4為Cl且R3、R5、R6係各自獨立為氫；(2)將式(III)化合物與雙(三甲基矽基)胺基鋰及一溴(C1-C20)烷醇於四氫呋喃中在0℃下進行反應，以獲得式(I)化合物 其中：R1為CH3、CH2CH3、CH(CH3)2、CH2CH(CH3)2或苯甲基；R2、R3、R4、R5及R6係各自獨立為氫；或R2、R4、R5及R6係各自獨立為氫且R3為CH3；或R2、R3、R5及R6係各自獨立為氫且R4為CH3、F、Cl或Br；或R2、R5、R6係各自獨立為氫、R3為OCH3且R4為Cl；或R3為Cl且R4為OCH3或R2、R4為Cl且R3、R5、R6係各自獨立為氫；且R7為(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH或(CH2)15OH， (3)將其中R1為苯甲基的式(I)化合物，與氫氣於壓力下透過鈀碳在室溫下於甲醇中進行反應，或與三氯化硼於二氯甲烷中在0℃下進行反應，以獲得式(I)化合物 R1、R2、R3、R4、R5及R6係各自獨立為氫；或R1、R2、R4、R5及R6係各自獨立為氫且R3為CH3；或R1、R2、R3、R5及R6係各自獨立為氫且R4為CH3、F、Cl或Br；或R1、R2、R5、R6係各自獨立為氫、R3為OCH3且R4為Cl；R3為Cl且R4為OCH3；或R2、R4為Cl且R1、R3、R5、R6係各自獨立為氫；且R7為(CH2)9OH、(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH或(CH2)15OH；或(4)將其中R1、R2、R3、R4、R5及R6係各自獨立為氫且R7為(CH2)11OH的式(I)化合物，與N-氯琥珀醯亞胺於氯甲烷中在室溫下進行反應，以提供式(I)化合物，其中R1、R3、R5及R6係各自獨立為氫、R2及R4係各自獨立為氯且R7為(CH2)11OH；或(5)將其中R1為甲基、R2、R3、R4、R5及R6係各自獨立為氫且R7為(CH2)11OH、(CH2)12OH或(CH2)13OH的式(I)化合物，與濃鹽酸、ICl3及冰 乙酸進行反應，以提供式(I)化合物，其中R1為甲基、R2、R3、R5及R6係各自獨立為氫、R4為Cl且R7為(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH、(CH2)15OH、(CH2)10OCOCH3、(CH2)11OCOCH3、(CH2)12OCOCH3或(CH2)13OCOCH3；或(6)將2-胺基苯酚與甲基乙烯基酮於鹽酸中進行反應，以獲得式(INT-1)化合物 (7)將式(INT-1)化合物與碘甲烷、碘乙烷、2-溴丙烷、亞甲基環丙基溴或溴甲苯於鹼性溶液中進行反應，以提供式(III)化合物 其中R10為甲基、乙基、2-丙基、亞甲基環丙基或苯甲基；(8)將其中R10為甲基、乙基、2-丙基、亞甲基環丙基或苯甲基的式(III)化合物，與雙(三甲基矽基)胺基鋰及11-溴-十一醇或12-溴十二醇於四氫呋喃中在0℃下進行反應，以獲得式(I)化合物，其中R1為甲基、乙基、2- 丙基、亞甲基環丙基或苯甲基；R2、R3、R4、R6及R7係各自獨立為氫；且R5為(CH2)11OH或(CH2)12OH；(9)將其中R1為苯甲基；R2、R3、R4、R6及R7係各自獨立為氫；且R5為(CH2)11OH或(CH2)12OH的式(I)化合物，與氫氣於壓力下透過鈀碳在室溫下於甲醇中進行反應，以獲得式(I)化合物，其中R1為氫；R2、R3、R4、R6及R7係各自獨立為氫；且R5為(CH2)11OH或(CH2)12OH；或(10)將2-三氟甲氧基苯胺與巴豆醛反應，以獲得2-甲基-8-三氟甲氧基喹啉，將其以雙(三甲基矽基)胺基鋰及一溴(C1-C20)烷醇於四氫呋喃中在0℃下進行處理，以獲得式(I)化合物，其中R1為三氟甲基；R2、R3、R4、R5及R6係各自獨立為氫；且R7為(CH2)10OH、(CH2)11OH、(CH2)12OH、(CH2)13OH或(CH2)15OH；或(11)將一式(IV)之8-羥基-2-甲基喹啉化合物，其中R1為氫、甲基、乙基、2-丙基或亞甲基環丙基 與二氧化硒於二【口+咢】烷中在升溫下進行反應，以提供一式(VI)化合物，R1為氫、甲基、乙基、2-丙基或亞甲基環丙基 式(VI)(12)將其中R1為氫、甲基、乙基、2-丙基或亞甲基環丙基之式(VI)化合物，與N-甲基丙炔胺進行反應，以獲得式(I)化合物，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2或CH(CH3)2、R2、R3、R4、R5及R6係各自獨立為氫；且R7為CH2N(CH3)CH2C≡CH；或(13)將R1為氫、甲基、乙基、2-丙基或亞甲基環丙基的式(VI)化合物，與2(哌【口+井】-1-基)乙醇進行反應，以獲得一式(I)化合物，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2或CH(CH3)2、R2、R3、R4、R5及R6係各自獨立為氫；且R7為CH2(N(CH2CH2)2N)CH2CH2OH；或(14)將式(VI)化合物與一胺基(C1-C20)烷醇進行反應以獲得一式(I)化合物，其中R1為氫、CH3、CH2CH3、CH2CH(CH3)2、CH2CH(CH2)2或CH(CH3)2；R2、R3、R4、R5及R6係各自獨立為氫；且R7為CH2NH(CH2)8OH或CH2N((CH2)6OH)CH2(8-甲氧基喹啉-2-基)。 A method of preparing the compound of claim 1, or a pharmaceutically acceptable salt thereof, comprising: (1) a compound of formula (II) Wherein: R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; or R 2 , R 4 , R 5 and R 6 are each independently hydrogen and R 3 is CH 3 ; or R 2 , R 3 , R 5 and R 6 are each independently hydrogen and R 4 is CH 3 , F, Cl or Br; or R 2 , R 5 , R 6 are each independently hydrogen, R 3 is OCH 3 and R 4 is Cl; or R 2 , R 4 are Cl and R 3 , R 5 , R 6 are each independently hydrogen, with bromotoluene, methyl iodide, ethyl iodide, 2-bromopropane or methylene cyclopropyl bromide The reaction is carried out in an alkaline solution at a temperature of from about room temperature to about 80 ° C to obtain a compound of the formula (III) Wherein: R 1 is CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 or benzyl; and R 2 , R 3 , R 4 , R 5 and R 6 are each Independently hydrogen; or R 2 , R 4 , R 5 and R 6 are each independently hydrogen and R 3 is CH 3 ; or R 2 , R 3 , R 5 and R 6 are each independently hydrogen and R 4 is CH 3 , F, Cl or Br; or R 2 , R 5 , R 6 are each independently hydrogen, R 3 is OCH 3 and R 4 is Cl; or R 2 , R 4 are Cl and R 3 , R 5 , R 6 is each independently hydrogen; (2) reacting a compound of formula (III) with bis(trimethylsulfonyl)amino lithium and monobromo(C 1 -C 20 ) alkanol in tetrahydrofuran at 0 ° C, To obtain a compound of formula (I) Wherein: R 1 is CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , CH 2 CH(CH 3 ) 2 or benzyl; R 2 , R 3 , R 4 , R 5 and R 6 are each independently Is hydrogen; or R 2 , R 4 , R 5 and R 6 are each independently hydrogen and R 3 is CH 3 ; or R 2 , R 3 , R 5 and R 6 are each independently hydrogen and R 4 is CH 3 , F, Cl or Br; or R 2 , R 5 , R 6 are each independently hydrogen, R 3 is OCH 3 and R 4 is Cl; or R 3 is Cl and R 4 is OCH 3 or R 2 , R 4 Is Cl and R 3 , R 5 , R 6 are each independently hydrogen; and R 7 is (CH 2 ) 9 OH, (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, ( CH 2 ) 13 OH or (CH 2 ) 15 OH, (3) reacting a compound of the formula (I) wherein R 1 is a benzyl group with hydrogen under pressure through palladium carbon at room temperature in methanol, or The reaction is carried out with boron trichloride in dichloromethane at 0 ° C to obtain a compound of formula (I) R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; or R 1 , R 2 , R 4 , R 5 and R 6 are each independently hydrogen and R 3 is CH 3 ; Or R 1 , R 2 , R 3 , R 5 and R 6 are each independently hydrogen and R 4 is CH 3 , F, Cl or Br; or R 1 , R 2 , R 5 , R 6 are each independently hydrogen. And R 3 is OCH 3 and R 4 is Cl; R 3 is Cl and R 4 is OCH 3 ; or R 2 , R 4 are Cl and R 1 , R 3 , R 5 , R 6 are each independently hydrogen; R 7 is (CH 2 ) 9 OH, (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH or (CH 2 ) 15 OH; or (4) Wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently a hydrogen and R 7 is (CH 2 ) 11 OH, a compound of formula (I), and N-chlorosuccinimide in chlorine The reaction is carried out in methane at room temperature to provide a compound of formula (I) wherein R 1 , R 3 , R 5 and R 6 are each independently hydrogen, and R 2 and R 4 are each independently chlorine and R 7 is ( CH 2 ) 11 OH; or (5) wherein R 1 is methyl, R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen and R 7 is (CH 2 ) 11 OH, (CH) 2) 12 OH or the compound (I) (CH 2) 13 OH formula with concentrated hydrochloric acid, ICl 3 and glacial acetic acid into , To afford Formula (I) compounds wherein R 1 is methyl, R 2, R 3, R 5 and R 6 are each independently hydrogen system, R 4 is Cl and R 7 is (CH 2) 10 OH, ( CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH, (CH 2 ) 15 OH, (CH 2 ) 10 OCOCH 3 , (CH 2 ) 11 OCOCH 3 , (CH 2 ) 12 OCOCH 3 Or (CH 2 ) 13 OCOCH 3 ; or (6) reacting 2-aminophenol with methyl vinyl ketone in hydrochloric acid to obtain a compound of formula (INT-1) (7) reacting a compound of the formula (INT-1) with methyl iodide, ethyl iodide, 2-bromopropane, methylene cyclopropyl bromide or bromine toluene in an alkaline solution to provide a compound of the formula (III) Wherein R 10 is methyl, ethyl, 2-propyl, methylenecyclopropyl or benzyl; (8) wherein R 10 is methyl, ethyl, 2-propyl, methylene cyclopropane Or a benzyl group of a compound of formula (III), which is reacted with bis(trimethylindenyl)amino lithium and 11-bromo-undecyl alcohol or 12-bromododecyl alcohol in tetrahydrofuran at 0 ° C to A compound of formula (I) wherein R 1 is methyl, ethyl, 2-propyl, methylene cyclopropyl or benzyl; R 2 , R 3 , R 4 , R 6 and R 7 are each independently Is hydrogen; and R 5 is (CH 2 ) 11 OH or (CH 2 ) 12 OH; (9) wherein R 1 is a benzyl group; R 2 , R 3 , R 4 , R 6 and R 7 are each independently a compound of formula (I) wherein R 5 is (CH 2 ) 11 OH or (CH 2 ) 12 OH, reacted with hydrogen under pressure through palladium on carbon at room temperature in methanol to obtain formula (I) a compound wherein R 1 is hydrogen; R 2 , R 3 , R 4 , R 6 and R 7 are each independently hydrogen; and R 5 is (CH 2 ) 11 OH or (CH 2 ) 12 OH; or (10) The 2-trifluoromethoxyaniline is reacted with crotonaldehyde to obtain 2-methyl-8-trifluoromethoxyquinoline, which is bis(trimethylsulfonyl)amine lithium and monobromide ( C 1 -C 20 ) alkane The alcohol is treated in tetrahydrofuran at 0 ° C to obtain a compound of formula (I) wherein R 1 is trifluoromethyl; R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; 7 is (CH 2 ) 10 OH, (CH 2 ) 11 OH, (CH 2 ) 12 OH, (CH 2 ) 13 OH or (CH 2 ) 15 OH; or (11) an 8-hydroxy group of the formula (IV) a -2-methylquinoline compound wherein R 1 is hydrogen, methyl, ethyl, 2-propyl or methylene cyclopropyl The reaction is carried out with selenium dioxide in dioxane at elevated temperature to provide a compound of formula (VI), R 1 being hydrogen, methyl, ethyl, 2-propyl or methylene cyclopropyl Formula (VI) (12) wherein a compound of formula (VI) wherein R 1 is hydrogen, methyl, ethyl, 2-propyl or methylene cyclopropyl is reacted with N-methylpropynylamine to A compound of formula (I) wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 or CH(CH 3 ) 2 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; and R 7 is CH 2 N(CH 3 )CH 2 C≡CH; or (13) R 1 is hydrogen, methyl, ethyl, 2 a compound of formula (VI), which is a propyl or methylene cyclopropyl group, is reacted with 2 (piperidin + well)-1-yl)ethanol to obtain a compound of formula (I) wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 or CH(CH 3 ) 2 , R 2 , R 3 , R 4 , R 5 and R 6 are each independently Hydrogen; and R 7 is CH 2 (N(CH 2 CH 2 ) 2 N)CH 2 CH 2 OH; or (14) reacting a compound of formula (VI) with an amine (C 1 -C 20 ) alkanol To obtain a compound of formula (I) wherein R 1 is hydrogen, CH 3 , CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , CH 2 CH(CH 2 ) 2 or CH(CH 3 ) 2 ; R 2 , R 3 , R 4 , R 5 and R 6 are each independently hydrogen; and R 7 is CH 2 NH(CH 2 ) 8 OH or CH 2 N ((CH 2 6 OH)CH 2 (8-methoxyquinolin-2-yl). 一種組成物，包括一治療有效量之請求項1至8中任一項所述之化合物或其醫藥可接受性鹽類，以及一醫藥可接受性稀釋劑或載劑。 A composition comprising a therapeutically effective amount of a compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier. 一種用於治療神經退化性疾病之組成物，包括一治療有效量之請求項1至8中任一項所述之化合物或其醫藥可接受性鹽類，以及一醫藥可接受性稀釋劑或載劑。 A composition for the treatment of a neurodegenerative disease, comprising a therapeutically effective amount of a compound of any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier Agent. 如請求項11所述之用於治療神經退化性疾病之組成物，其中該神經退化性疾病係選自由以下疾病所組成之群組：阿茲海默症、肌萎縮性側索硬化症(ALS)、認知失調、缺血性腦中風、腦性麻痺、中風、出血性中風、庫 賈氏症、海綿樣腦病變、狂牛症、癡呆症、憂鬱症、唐氏症、癲癇、額顳葉癡呆症、妥瑞氏症、哈斯氏症(Hallerboden-Spatz disease)、亨丁頓氏症、路易氏體疾病、帕金森氏症、認知障礙、學習障礙、黃斑部病變、記憶障礙、多發性硬化症、多發性系統萎縮、運動神經元疾病、匹克氏症、漸進性核上麻痺、假性痴呆症、視網膜病變、老年癡呆症、精神分裂症暫時性缺氧誘發之神經退化、創傷性腦損傷及脊髓損傷。 The composition for treating a neurodegenerative disease according to claim 11, wherein the neurodegenerative disease is selected from the group consisting of Alzheimer's disease, amyotrophic lateral sclerosis (ALS) ), cognitive disorders, ischemic stroke, cerebral palsy, stroke, hemorrhagic stroke, library Jasmine, spongiform encephalopathy, mad cow disease, dementia, depression, Down's syndrome, epilepsy, frontotemporal dementia, Tourette's disease, Hallerboden-Spatz disease, Huntington's disease Disease, Lewis' disease, Parkinson's disease, cognitive impairment, learning disabilities, macular degeneration, memory impairment, multiple sclerosis, multiple system atrophy, motor neuron disease, Pick's disease, progressive supranuclear palsy, Pseudodementia, retinopathy, Alzheimer's disease, neurodegeneration induced by temporary hypoxia, schizophrenia, traumatic brain injury, and spinal cord injury. 如請求項11所述用於治療神經退化性疾病之組成物，其中該神經退化性疾病為阿茲海默症。 The composition for treating a neurodegenerative disease according to claim 11, wherein the neurodegenerative disease is Alzheimer's disease. 一種請求項1至8中任一項所述之化合物或其醫藥可接受性鹽類用於製備一神經退化性疾病治療用藥物的用途。 Use of a compound according to any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof for the preparation of a medicament for the treatment of a neurodegenerative disease. 如請求項14所述之用途，其中該藥物係用於治療阿茲海默症。 The use of claim 14, wherein the medicament is for the treatment of Alzheimer's disease.
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