TW591006B

TW591006B - Novel anthracenedione analogues and process of preparation thereof

Info

Publication number: TW591006B
Application number: TW88119382A
Authority: TW
Inventors: Huei-Po Wang; Lian-Tz Li; Ang Li
Original assignee: Huei-Po Wang
Priority date: 1999-11-05
Filing date: 1999-11-05
Publication date: 2004-06-11

Abstract

A series of novel 9, 10-anthracenedione of formula (I), wherein said n is an integer from 1 to 6; R or R' is independently H or hydroxyl; R1 or R1' is independently H or alkyl; R2 or R2' is independently H, alkyl or alkyl having a substitutable group with a functional group; R3 or R3' is independently H; or R3, R4 are taken together as -(CH2)x- wherein said X is 4, 5 or 6; or R3', R4' are taken together as -(CH2)x- wherein said X is 4, 5 or 6; R4 or R4' is independently H, formyl, alkylcarbonyl, alkoxycarbonyl or arylmethoxycarbonyl; is disclosed.

Description

591006 Λ7 B7591006 Λ7 B7

五、發明說明（/ ) m 5.11 #Γ定」【本發明之領域】本發明係關於一種新穎胺基驢基蒽醒化合物，尤指種適用於抗腫瘤藥物之新穎胺基醯基蒽醌化合物。【本發明之背景】已知 Ametantrone 及 mitoxantrone (如下户斤一、V. Description of the invention (/) m 5.11 # Γ 定 "[Field of the invention] The present invention relates to a novel amino donkey anthracene compound, especially a novel amino amidino anthraquinone compound suitable for antineoplastic drugs. . [Background of the invention] Ametantrone and mitoxantrone are known (as follows:

(請先閲讀背面之注意事頊再填寫本頁) 經濟部智慧財產咼員工消費合阼fi-卞段為具有9，10 -蒽醌（anthracenedione)結構之抗腫瘤臨床藥物。此類具有9，1 0 -蒽醌結構之抗腫瘤藥物因為具有平面結構，故能嵌入B構型DNA之鹼基對中，進而影響 DNA之正常功能。而9,10-蒽醌化合物，若要具有對聚核苷酸之磷酸酯骨架具有作用力，蒽醌化合物結構上之取代基’通常需有正電荷基團形成靜電作用力。而平面狀蒽破結構與取代基間之相關位置，會影響蒽醌化合物整體分子與拓樸異構酶II作用之強弱，進而決定藥物活性大小與抗藥性產生與否。現今使用之Ametaim〇ne及 mitoxantrone，常因為部分癌細胞拓樸異構酶13[突變，或是部分癌細胞細胞膜通透性發生改變，故而有抗藥性之問題。是以亟需發展一種可以解決抗藥性問題之9，1〇-蒽本紙張尺！過用T國國冢標準（CNS)A4規格（2】0 X 297公沒） ▼裝--------訂---------線* H—r2, 〇 N—R3* r4· 591006 第88119382號，92年12月修正頁五、發明說明（2 ) 酉昆（anthracenedione)結構之臨床藥物，以應用於腫瘤之治療。發明人麦因於此，s思一種可以解決上述問題之「新穎胺基醯基蒽醌化合物」’幾經研究實驗完成此項發明。【本發明之概述】本电明之主要目的係在提供—種新賴之具有9，1〇_葱醌（anthraCenedi〇ne)結構之化合物，俾能降低部分癌細胞之抗藥性。本發明之次要目的係在提供一種包含新穎之具有 9，10-蒽醌（anthracenedi〇ne)結構之化合物之醫藥組成物’俾能降低癌細胞之抗藥性。本發明之新穎之具有9，1〇-葱醌(anthracenedione) 結構之化合物如式（I )所示 Ο N—R3 -(CH2)n—N一一C—R2 〇 HN—(CH2)r 其中n為1至6之任一整數，R或R，各自獨立地為氫或氫氧基，汉丨或！^’各自獨立地為氫或具1至6個碳原子之基’· h或R2,各启獨立地為氫，具1至6個碳原子之基或具官能性基團取代基之烷基；R3或R3，各自獨立地為氫 4R3、RJ^g-(CH2)xJtx*4、5 46’1 本紙張尺度適用中關家標準（CNSM4規格咖X 297公爱 0^--------^--------- (請先閱讀背面之注意事項再填寫本頁) 591006 Λ7 B7 ^;i補充五、發明說明（3 ) R3’、R4’共同為-(CH2) χ·其中 x為4、5 或6 ; R4 或 r4, 各自獨立地為氫、甲醯基（formyl )、烷缓基 (alkylcarbonyl )、烷氧羰基（alkoxycarbonyl )或方香族统甲乳後基（arylmethoxycarbonyl) 〇由於本發明化合物構造新穎，能提供產業上利用，且確有增進功效，故依法申請發明專利。【較佳具體實施例之詳細説明】本發明之新穎之具有9，10-蒽醌（anthraCenedione) 結構之化合物如式（I )所示 Ο N——R3 〇(Please read the cautions on the back and then fill out this page.) The intellectual property of the Ministry of Economic Affairs, the employee consumption, and the fi-section are clinical antitumor drugs with a 9,10-anthracenedione structure. This type of antitumor drug with a 9,10-anthraquinone structure has a flat structure, so it can be embedded in the base pair of the B-configuration DNA, thereby affecting the normal function of the DNA. On the other hand, if the 9,10-anthraquinone compound has an effect on the phosphoric acid ester backbone of the polynucleotide, the substituent on the anthraquinone compound's structure usually needs a positively charged group to form an electrostatic force. The related position between the planar anthracene structure and the substituents will affect the strength of the anthraquinone compound's overall molecule and the topoisomerase II, and then determine the level of drug activity and resistance. Ametaimone and mitoxantrone used today often have drug resistance problems because of some cancer cell topoisomerase 13 [mutations or changes in the permeability of the cell membrane of some cancer cells. Therefore, there is an urgent need to develop a 9,10-anthracene paper rule that can solve the problem of drug resistance! Used the National Takayama Standard (CNS) A4 specification (2) 0 X 297 public) ▼ installed -------- order --------- line * H—r2, 〇N— R3 * r4 · 591006 No. 88119382, revised in December 1992 Page V. Description of the Invention (2) Clinical drugs with anthracenedione structure, used in the treatment of tumors. Because of this, the inventor, Mai, thinks of a "neuraminyl fluorenyl anthraquinone compound" that can solve the above problems, and has completed this invention after several research experiments. [Summary of the present invention] The main purpose of the present invention is to provide a novel compound having an anthraCenedione structure which can reduce the resistance of some cancer cells. A secondary object of the present invention is to provide a pharmaceutical composition including a novel compound having a 9,10-anthracenedione structure, which can reduce the resistance of cancer cells. The novel compound having a structure of 9,10-anthracenedione of the present invention is represented by formula (I). 0 N-R3-(CH2) n-N-C-R2 〇HN- (CH2) r where n is any integer from 1 to 6, R or R, each independently is hydrogen or hydroxyl, Han or! ^ 'Each independently is hydrogen or a group having 1 to 6 carbon atoms' h or R2, each is independently hydrogen, an alkyl group having 1 to 6 carbon atoms or an alkyl group having a functional group substituent ; R3 or R3, each independently is hydrogen 4R3, RJ ^ g- (CH2) xJtx * 4, 5 46'1 This paper size applies the Zhongguanjia standard (CNSM4 specification coffee X 297 public love 0 ^ ----- --- ^ --------- (Please read the notes on the back before filling out this page) 591006 Λ7 B7 ^; i Supplement V. Description of the invention (3) R3 'and R4' are-(CH2 ) χ, where x is 4, 5, or 6; R4 or r4, each independently is hydrogen, formyl, alkylcarbonyl, alkoxycarbonyl, or fragrant aromatic milk Aryl (methoxymethoxycarbonyl) 〇 Because the compound of the present invention is novel in structure, can provide industrial use, and indeed has enhanced efficacy, it applies for an invention patent in accordance with the law. [Detailed description of preferred specific embodiments] The novelty of the present invention has 9,10- AnthraCenedione compounds are represented by formula (I): N—R3.

η II I 訂一(CH2)n—N—C—c—R2 R1 R' 〇η II I Order (CH2) n-N-C-c-R2 R1 R '〇

Hhi (CH2)n—N—C—C—R2 丨〇 N——R3_ 線式（I ) 其中n為1至6之任一整數，n較佳為2或3;尺或化，各自獨jl地為為氫或氫氧基，R或R，較佳為氫或相同之基團； R!或尺！’各自獨立地為氫或具！至6個碳原子之烷基，或1^ ’較佳為相同之基團；尺2為氫或垸基，R2或R2，各自獨立地為氫、具丨至6個碳原子之垸基或具官能性基團取代基之垸基，R3或R3,較佳為相同之基目；而該官能性基團可為氬氧基、胺基、膽（carbamide)、氨基甲酿基 (carbamyl) 、味啦其 ( , y ^ ^ ( carbazoyl )、羧基本紙張尺度適用中關家標準（CNS；)A4規格（2】〇 X 297如丁 591006 A7 B7Hhi (CH2) n—N—C—C—R2 丨〇N——R3_ Linear formula (I) where n is any integer from 1 to 6, n is preferably 2 or 3; ruler or chemistry, each independently jl Ground is hydrogen or hydroxyl, R or R, preferably hydrogen or the same group; R! Or ruler! ’Each independently is hydrogen or a tool! Alkyl groups of 6 to 6 carbon atoms, or 1 ^ 'is preferably the same group; Chi 2 is hydrogen or fluorenyl, and R 2 or R 2 are each independently hydrogen, fluorenyl or A fluorenyl group having a functional group substituent, R3 or R3, is preferably the same group; and the functional group may be argoxy, amine, carbamide, carbamyl 、味啦其 (, y ^ ^ (carbazoyl), carboxyl paper size is applicable to Zhongguanjia standard (CNS;) A4 specification (2) 0X 297 Ruding 591006 A7 B7

五、發明說明（4) (carboxyl )、後基（carbonyl )、甲醯基 (formyl )、硫醇基（mercapto )、甲基硫代基 (m e t h y 11 h i 〇 )、硫代聪基（t h i 〇 u r e i d 〇 )、硫代腈基 (thiocyanato )、績胺基（sulfoamoyl )、績基 (sulfo)、膦基（phosphono)、敦基（fluoro)、氣基（chloro)、溴基（bromo)、破基（iodo)、腈基 (cyano)、三氟甲基（trifluoromethyl)或具以下結構式基團 -(CH2)m-R7 其中m為0至3之整數，117為1-萘基（1-naphthyl ) 、2- 萘基（2-naphthyl) 、2-呋喃（2-furyl) 、3-呋喃（3-furyl ) 、2-¾ 吩基（2-thienyl ) 、3-喧吩基（3-thienyl ) 、2-咯咯基（2-pyrrolyl ) 、3_ 咯咯基（3-pyrrolyl) 、2-咯啶基（2-pyridyl) 、2·咪唑基（2-imidazolyl) 、4-咪唑基（4_imidazolyl) 、2 -叫噪基 (2-indolyl) 、3-叫哚基（3-indolyl) 、3-咯啶基（3-pyridyl ) 、4 -咯啶基（4-pyridyl ) 、2-嘧啶基（ pyrimidinyl) 、4 -嘧啶基（4_pyrimidinyl) 、5-π 密口定基（5-pyrimidinyl)或具以下結構式基團V. Description of the invention (4) (carboxyl), carbonyl, formyl, mercapto, methylthio (methy 11 hi), thio (thio) ureid 〇), thiocyanato, sulfoamoyl, sulfo, phosphono, fluoro, chloro, bromo, broken group (Iodo), cyano, trifluoromethyl, or a group having the formula:-(CH2) m-R7 where m is an integer from 0 to 3, and 117 is 1-naphthyl ), 2-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl ), 2-pyrrolyl (2-pyrrolyl), 3-pyrrolyl (2-pyridyl), 2-imidazolyl (2-imidazolyl), 4-imidazolyl (4-imidazolyl), 2-called 2-indolyl, 3-indolyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl ), 4-pyrimidinyl (5-pyrimidinyl) (idinyl) or a group having the following structural formula

—(ch2), 氫氧、咔 (請先閱讀背面之注意事項再填寫本頁) 其中m為0至3之整數，R5及各個別獨立地為氫基、脲（carbamide)、氨基甲醯基（carbamyl 90.591006 Λ7 B7 V修正丨五、發明說明（5* ) -----------------二^」唾基（carbazoyl )、羧基（carb〇xyl )、羰基 (carbonyl )、甲醯基（formyl )、硫醇基 (mercapto )、甲基硫代基（methylthio )、硫代脲基 (thioureido )、硫代腈基（thiocyanato )、磺胺基 (sulfoamoyl ) 、磺基（sulfo ) 、膦基 (phosphono )、氟基（fluoro )、氯基（chloro )、溴基（bromo)、破基（i〇do)、腈基（ cyano )、三氟甲基（trifluoromethyl)、具1至6個碳原子之垸基、具 1至6個碳原子之垸氧基、二甲基胺基及苯甲基氧基 (benzyloxy) ; R3或R3’各自獨立地為氫，以3或尺3，較佳為相同之基團；或R3、R4共同為-(CH2) X-其中X為4、 5或6 ;或R3’、R4’共同為-(CH2 ) x-其中X為4、5或6 ; R4或R4’各自獨立地為氫、甲酸基（formyl)、具1至18 個碳原子之燒疑基（alkylcarbonyl)、具1至18個碳原子之院氧談基（alkoxycarbonyl)或芳香族燒甲氧談基 (arylmethoxycarbonyl)，其中芳香族烷基團為苯基、2-甲氧苯基、4-甲氧苯基、2-氟苯基 (fluorophenyl ) 、 4-氟苯基、2-氯苯基 (chlorophenyl ) 、 4-氯苯基、2-溴苯基 (bromophenyl ) 、4 -溴苯基(bromophenyl ) 、1-萘基（Ι-naphthyl )、 2-萘基（2-naphthyl )、 9-苟基 (9-fluorenyl ) 、2-吱喃（2-fury 1 ) 、3-咬喃（3- furyl )、2-噻吩基（2-thienyl )、3-噻吩基（ thienyl) 、2 -咯啶基（2-pyridyl) 、3 -咯啶基（3- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297 Θ釐） (請先閱讀背面之注意事項再填寫本頁) ▼裝--------訂---------線4 591006 I 5. 11 /r 年月R β— (Ch2), Hydrogen, Oxygen (please read the notes on the back before filling this page) where m is an integer from 0 to 3, R5 and each are independently hydrogen, urea (carbamide), carbamate (Carbamyl 90.591006 Λ7 B7 V amendments 丨 5. Description of the invention (5 *) ----------------- two ^ "carbazoyl, carboxyl (carboxyl), carbonyl (carbonyl), formyl, mercapto, methylthio, thioureido, thiocyanato, sulfoamoyl, sulfo Sulfo, phosphono, fluoro, chloro, bromo, iodo, cyano, trifluoromethyl , A fluorenyl group having 1 to 6 carbon atoms, a fluorenyl group having 1 to 6 carbon atoms, dimethylamino group and benzyloxy; R3 or R3 'are each independently hydrogen, and 3 or 3, preferably the same group; or R3 and R4 are-(CH2) X- where X is 4, 5 or 6; or R3 'and R4' are-(CH2) x- where X Is 4, 5, or 6; R4 or R4 'are each independently Hydrogen, formyl, alkylcarbonyl with 1 to 18 carbon atoms, alkoxycarbonyl or aromatic arylcarbonyl with 1 to 18 carbon atoms, The aromatic alkyl group is phenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 4- Chlorophenyl, 2-bromophenyl, 4-bromophenyl, 1-naphthyl, 2-naphthyl, 9-fluorenyl ), 2-fury (2-fury 1), 3-furyl (2-furyl), 2-thienyl (thienyl), 3-thienyl (thienyl), 2-pyridyl (2-pyridyl) ), 3 -pyridinyl (3- This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 Θ centimeters) (Please read the precautions on the back before filling out this page) ▼ Install ------ --Order --------- line 4 591006 I 5. 11 / r year month R β

五、發明說明（6 ) pyridyl ) (f1、4Κ基（）或五氣苯基 (=Π——) A或V較佳為相同之基圈；以及其樂學上可接受之鹽類。本發明之式⑴之化合物較佳為化合物：如式（II )所示之V. Description of the invention (6) pyridyl) (f1, 4K group () or pentafluorophenyl (= Π——) A or V are preferably the same base ring; and musically acceptable salts thereof. The compound of formula VII of the invention is preferably a compound: as shown by formula (II)

^8 凡· 式（II ) (請先閱讀背面之注意事項再填寫本頁)^ 8 Where (II) (Please read the precautions on the back before filling this page)

經濟部智慧財產局員工消費合泎fi印別R 其中Rs或Rs’各自獨立地為甘氨基酸基（glycinyl )、初油氨基酸基（alaninyl)、香氨基酸基（valinyl)、白氨基酸基（lencinyl)、異白氨基酸基（is〇ieucinyl)、普林基（prolinyl)、+初油氣基酸基（phenyiaianyi)、甲硫氨基基（methionyl)、色氨基酸基（trypt〇phyi)、絲氨基酸基（serinyl)、異絲氨基酸基（threoninyi)、半胱氨基酸基（cysteinyl)、膠氨基醯胺基（giutarninyl)、α-膠氨基酸基（α-glutamyl)、γ-膠氨基酸基（γ-glutamyl)、酪氨基酸基（tyrosinyl)、天冬氨基醯胺基（asparaginyl)、 α-天冬氨基酸基（α-aspartyl)、β-天冬氨基酸基（β-aspartyl)、溶氨基酸基（lysinyl)、蛋白氨基酸基 (argininyl)、組織氨基酸基（histidinyl)、N -第三丁氧羧甘氨基酸基（N-Boc-glycinyl)、N-第三丁氧凝初油氨本紙張尺度適用中國國家標準（CNS)A4規格（2】0 X 297 $釐） 90. 5. ί 1 倏正補充 591006 A? ___B? 五、發明說明（7 ) 基酸基（N-Bo^Uninyl)、Ν：^三丁^氨基酸基 (N-Boc-valinyl)、Ν-第三丁氧羰白氨基酸基（ν_β〇 leucinyl)、Ν_第三丁氧羰異白氨基酸基（ν_β〇 isoleucinyl) 、Ν-第三丁氧羰普林基（n_b〇c prolinyl)、N-第三丁氧羰苯初油氨基酸基（N-B〇c phenylalanyl)、N-第三丁氧羰甲硫氨基酸基（nb〇c methionyl)、N-第三丁氧羰色氨基酸基（n_b〇c tryptophyl)、N-第三丁氧羰絲氨基酸基（n_b〇c serinyl)、N_第三丁氧羰異絲氨基酸基（n_b〇c threoninyl)、N_第三丁氧羰半胱氨基酸基（n_b〇c cysteinyl)、N-第三丁氧羰膠氨基醯胺基（N_B〇c glutaminyl)、Να-第三丁氧羰_α•膠氨基酸基（Na-]Boc α-glutamyl)、Να·第三丁氧羰_γ_膠氨基酸基（Na_B〇c-Y glutamyl)、N-第三丁氧羰酪氨基酸基（N-B〇c tyrosinyl)、N-第三丁氧羰天冬氨基醯胺基（N_B〇c asparaginyl)、Να-第三丁氧羰_α_天冬氨基酸基 Boc-a-aspartyl)、Να-第三丁氧羰-β_天冬氨基酸基 Boc-p-aspartyl)、Ν-第三丁氧羰溶氨基酸基（n-Boc lysinyl)、Να，Νε-二第三丁氧羰溶氨基酸基（ν' Νε diBoc-lysinyl)、N -第三丁氧羰蛋白氨基酸基（N-Boc argininyl)、Na，NM-二第三丁氧羰蛋白氨基酸基（Να Nguanidiny丨-diBoc-argininyl ) 、Ν-第三丁氧羰組織氨；| 酸基（]^-：8〇(：-11丨51丨(1丨11}^)、>^-苯甲基氧羰基-甘氨基酸；| 嘬 (N-Cbz-glycinyl ) 、N -苯甲基氧缓基-初油氨基酸基本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） (請先閱讀背面之注音？事項再填寫本頁) -裝--------訂---------線一經濟部智慧財產局員工消費合作社印製 591006 補充丨 A7 _________ B7 90~TTT^ ^ 五、發明說明（<? (N-Cbz-alaninyl)、N-苯甲基氧羰基-香氨基酸基（Να z-valinyl) 、 N-苯甲基氧羰基-白氨基酸基（N-Cbz-leucinyl)、N-苯甲基氧羰基-異白氨基酸基（N — Cbz-isoleucinyl)、N-苯甲基氧羰基-普林基（N-Cbz-prolinyl) 、 N_ 苯甲基氧羰基-初油氨基酸基⑺—^心 phenylalany 1)、N-苯甲基氧羰基-甲硫氨基酸基（N_ Cbz-methionyl)、Ν·苯甲基氧羰基-色氨基酸基（N-Cbz__ tryptophyl)、N-苯甲基氧羰基-絲氨基酸基（N-Cbz-serinyl) 、 N- 苯甲基氧羰基 - 異絲氨基酸基（N_Cbz-threoninyl)、N-苯甲基氧羰基—半胱氨基酸基（N-Cbz_ cysteinyl)、N-苯甲基氧羰基-膠氨基醯胺基（N-Cbz-glutaminyl)、Να-苯甲基氧羰基-α_膠氨基酸基（1^_ Cbz-a-glutamyl)、Να_苯甲基氧羰基_γ_膠氨基酸基 (Na-Cbznlutamyl)、Ν-苯甲基氧羰基酪氨基酸基（N-Cbz-tyroSinyl)、N-苯甲基氧羰基天冬氨基醯胺基（N-Cbz-asparaginyl)、Να-苯甲基氧羰基-α_天冬氨基酸基 (Na- Cbz-cx-aspartyl)、Να-苯甲基氧羰基_0_天冬氨基酸基（化-〇2邛4”31^1)、心苯甲基氧羰基溶氨基酸基 (N-Cbz-lysinyl)、Να，Νε-二苯甲基氧羰基溶氨基酸基 (Na，N、diCbz-lysiiiy 1)、苯甲基氧羰基蛋白氨基酸基（N_Cbz-argininyl)、Na，Ν·基-二苯甲基氧羰基蛋白氨基酸基（Na，Nguanidinyl-diCbZ-argininyl) 、N-苯甲基氧羰基組織氨基酸基（N-Cbz-histidinyl) 、N- (9-% )甲氧基-甘氨基酸基（N-Fmoc-glycinyl)、N- (9- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297义釐) (請先閱讀背面之注意事項再填寫本頁) -裝------—訂---------線一經濟部智慧財產局員工消費合作fi印ΜEmployees of the Intellectual Property Bureau of the Ministry of Economic Affairs, the consumption of Fibonacci R, where Rs or Rs' are each independently glycinyl, alaninyl, valinyl, and lencinyl , Isoleucinyl, prolinyl, + phenyiaianyi, methionyl, trypt〇phyi, serinyl ), Threoninyi, cysteinyl, giutarninyl, α-glutamyl, γ-glutamyl, casein Amino acid group (tyrosinyl), asparaginyl group, asparaginyl group, α-aspartyl group, β-aspartyl group, lysinyl group, protein amino acid group (argininyl), tissue amino acid group (histidinyl), N-Boc-glycinyl amino group, N-Boc-glycinyl amino group. This paper applies Chinese National Standard (CNS) A4. Specifications (2) 0 X 297 $ cents 90. 5. ί 1 倏 is supplementing 591006 A? ___B? V. Description of the invention (7) N-Bo ^ Uninyl, N: ^ tributyl ^ amino acid (N-Boc-valinyl), N-third butoxy Carbonyl white amino acid group (ν_β〇leucinyl), N_third butoxycarbonyl iso white amino acid group (ν_β〇isoleucinyl), N-third butoxycarbonyl prolinyl (n_b〇c prolinyl), N-third butoxy N-boc phenylalanyl, N-bocc methionyl, N-bocc tryptophyl, N- The third butoxycarbonyl silk amino acid group (n_bocc serinyl), the N_third butoxycarbonyl isoselin amino acid group (n_bocc threoninyl), the N_third butoxycarbonyl cysteine amino acid group (n_bocc cysteinyl) N-Bocc glutaminyl, Nα-Bocc-glutaminyl group, Na-Boc α-glutamyl, Nα-bocamino group _γ_ gum amino group (Na_Bocc glutamyl), N-third butoxycarbonyl tyrosinyl group, N-third butoxycarbonyl asparaginyl group (N_B〇c asparaginyl), Να-third butoxycarbonyl_α_Asparagus Amino acid group Boc-a-aspartyl), Nα-third butoxycarbonyl-β-aspartic acid group Boc-p-aspartyl), N-third butoxycarbonyl-soluble amino acid group (n-Boc lysinyl), Να, Νε -Two third butoxycarbonyl soluble amino acid group (ν 'Νε diBoc-lysinyl), N-third butoxycarbonyl protein amino acid group (N-Boc argininyl), Na, NM-two third butoxycarbonyl protein amino acid group ( Να Nguanidiny 丨 -diBoc-argininyl), N-third butoxycarbonylhistamine; | acid group (] ^-: 8〇 (:-11 丨 51 丨 (1 丨 11} ^), > ^-benzyl Oxycarbonyl-glycine; | 嘬 (N-Cbz-glycinyl), N-benzyloxy retarder-primary oil amino acid The basic paper size applies to Chinese National Standard (CNS) A4 (210 X 297 mm) (please Read the Zhuyin on the back? (Please fill in this page again for matters)-Install -------- Order --------- Printed by the Consumers Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 591006 Supplement 丨 A7 _________ B7 90 ~ TTT ^ ^ 5 Description of the invention (<? (N-Cbz-alaninyl), N-benzyloxycarbonyl-aromatic amino group (Nα z-valinyl), N-benzyloxycarbonyl-white amino acid group (N-Cbz-leucinyl ), N-benzyloxycarbonyl-isoleucinyl, N-Cbz-isoleucinyl, N-Cbz-prolinyl, N_benzyloxycarbonyl-virgin oil Amino acid group ^ —phenylalany 1), N-benzyloxycarbonyl-methylthioamino group (N_Cbz-methionyl), N-benzyloxycarbonyl-color amino acid group (N-Cbz__tryptophyl), N-benzene Methyloxycarbonyl-serine amino group (N-Cbz-serinyl), N-benzyloxycarbonyl-isoserine amino group (N_Cbz-threoninyl), N-benzyloxycarbonyl-cysteine amino group (N-Cbz_ cysteinyl), N-benzyloxycarbonyl-glyaminoamino (N-Cbz-glutaminyl), Nα-benzyloxycarbonyl-α_glycine amino group (1 ^ _ Cbz-a-glutamyl), Να_ Benzyloxycarbonyl_γ_glycine amino group (Na-Cbzn lutamyl), N-benzyloxycarbonyl tyrosamino group (N-Cbz-tyroSinyl), N-benzyloxycarbonyl aspartamidoamine (N-Cbz-asparaginyl), Nα-phenylmethyloxycarbonyl- α-aspartic acid group (Na-Cbz-cx-aspartyl), Να-benzyloxycarbonyl group_0_aspartic acid group (Chemical-〇2 邛 4 ”31 ^ 1), cardiac benzyloxycarbonyl group Amino acid group (N-Cbz-lysinyl), Nα, Νε-benzyloxycarbonyl amino acid group (Na, N, diCbz-lysiiiy 1), benzyloxycarbonyl protein amino acid group (N_Cbz-argininyl), Na, N · yl-diphenylmethyloxycarbonyl protein amino acid group (Na, Nguanidinyl-diCbZ-argininyl), N-benzyloxycarbonyl tissue amino acid group (N-Cbz-histidinyl), N- (9-%) methoxy N-Fmoc-glycinyl, N- (9- This paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 meanings) (Please read the precautions on the back before filling this page) -Installation -------- Order --------- Line 1 Intellectual Property Bureau, Ministry of Economic Affairs, Consumer Cooperation

591006591006

五、發明說明（9) L--------------------------J 知）甲乳基-初油氣基酸基（N-Fmoc-alaninyl)、N_ (9_ 勿）甲乳基-香氣基酉艾基（N-Fmoc-valinyl)、N- ( 9_ 勿）甲乳基-白氣基故基（N-Fmoc-leucinyl)、N- (9_ 勿）甲乳基-異白氣基基（N-Fmoc-isoleucinyl) 、N- (9-¾ )甲氧基-初油氣基酸基（N_Fmoc-alaninyl)、N- (9-¾ )甲乳基·香氨基酸基（N_Fmoc_vaiinyi)、N- (9-¾ )甲乳基·白氨基酸基（N-Fmoc-leucinyl)、N- (9-¾ )甲乳基-異白氨基酸基（N-Fmoc-isoleucinyl)、 N- (9-¾ )甲乳基-普林基（N-Fmoc-prolinyl)、N- (9- 勿）甲乳基-初油氣基酸基（N-Fmoc-phenylalanyl)、N- (9-¾ )甲乳基-甲硫氨基酸基（N-Fmoc_methionyl)、 N- (9-¾ )甲氧基-色氨基酸基（N_Fmoc-tryptophyl)、 N- ( 9 -芴）甲氧基-絲氨基酸基（n -Fmoc-serinyl)、N- (9-¾ )甲氧基-異絲氨基酸基（N-Fmoc-threoninyl)、 N- (9-勿）甲乳基-半脱氨基酸基（N-Fmoc- cysteinyl) 、 N- ( 9- 芴）甲氧基 - 膠氨基醯胺基（N_V. Description of the invention (9) L -------------------------- J Known) Methyl emulsion-primary hydrocarbon-based acid group (N-Fmoc -alaninyl), N_ (9_）) methyl milk base-aroma base N-Fmoc-valinyl, N- (9_) methyl milk base-white air base (N-Fmoc-leucinyl), N -(9_ Don't) N-Fmoc-isoleucinyl, N- (9-¾) methoxy-N-Fmoc-alaninyl, N- (9-¾ ) N-Fmoc_vaiinyi, N- (9-¾) N-Fmoc-leucinyl, N- (9-¾) N-Fmoc-leucinyl, N-Fmoc-isoleucinyl), N- (9-¾), N-Fmoc-prolinyl, N- (9- be), N-Fmoc-prolinyl, N-Fmoc- phenylalanyl), N- (9-¾) methyllactyl-methionyl amino group (N-Fmoc_methionyl), N- (9-¾) methoxy-color amino acid group (N_Fmoc-tryptophyl), N- (9-芴) N-Fmoc-serinyl, N- (9-¾) N-Fmoc-threoninyl, N- (9-Do) methyllactyl- Semi-deamino acids (N-Fmoc-cysteinyl), N- (9-fluorene), methoxy-glycine Acyl amino (N_

Fmoc-glutaminyl) 、Να- (9-芴）甲氧基-α-膠氨基酸基（Na-Fmoc-cx-glutamyl)、Na- (9-芴）甲氧基-γ-膠氨基酸基（Na-Fmoc-y-glutamyl)、N- (9-芴）甲氧基-酪氨基酸基（N-Fmoc-tyrosinyl)、N- (9-芴）甲氧基-天冬氨基醯胺基（N-Fmoc-asparaginyl)、Να- (9-苗）甲氧基-α·天冬氨基酸基（Na-Fmoc-a_aspartyl)、Να- (9- 芴）甲氧基-β_天冬氨基酸基（Na-Fmoc-p-aspartyl)、 N- (9-芴）甲氧基溶氨基酸基（N-Fmoc-lysinyl)、Να， ___ _12___ 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公釐） -----I I-----------I I 訂·! ----I (請先閱讀背面之注意事項再填寫本頁)Fmoc-glutaminyl), Να- (9- 芴) methoxy-α-glycine amino group (Na-Fmoc-cx-glutamyl), Na- (9- 芴) methoxy-γ-glycan amino acid group (Na- Fmoc-y-glutamyl), N- (9- 芴) methoxy-tyrosinyl, N- (9- 芴) methoxy-aspartylamino (N-Fmoc -asparaginyl), Να- (9- 苗) methoxy-α · aspartic acid group (Na-Fmoc-a_aspartyl), Να- (9-fluorene) methoxy-β_aspartic acid group (Na-Fmoc -p-aspartyl), N- (9- 芴) methoxyl-soluble amino acid group (N-Fmoc-lysinyl), Nα, ___ _12___ This paper size applies to China National Standard (CNS) A4 (210 X 297 mm) ----- I I ----------- II Order ·! ---- I (Please read the notes on the back before filling this page)

經濟部智慧財查咼員1肖f合泎，fi.pyA 5910061 Smart Financial Investigation Officer, Ministry of Economic Affairs, Xiao Xiaohe, fi.pyA 591006

Νε-二（9-芴）甲氧基-溶氨基酸基（Να，N、diFm〇c_ lysinyl)、N- (9-苟）甲氧基-蛋白氨基酸基（N_Fm〇c_ argininyl)、N' NgUanmnyi_ 二（9 一芴）甲氧基 _ 蛋白氨基酸基（Ν' Ng_idinyLdiFm〇c_argininyi) 、n_ & 芴）甲氧基-組織氨基酸基（]^邛111〇(^11丨以丨〇1丨1^1)、1^-第二丁氧緩_ Νε-苯甲基氧羰基-溶氨基酸基（Na-]B〇C- Νε_ Cbz_ lySinyl)、NL第三丁氧羰_ Ν、苯甲基氧羰基-溶氨基故基（Νε - Β 〇 c - Ν α - C b z - 1 y s i n y 1)、Ν α -第三丁氧缓_ Νε- ( 9 -芴）甲氧基-溶氨基酸基（n«_b〇c- N^Fm〇c-lysinyl)、Νε-第三丁氧羰-（9-芴）甲氧基-溶氨基酸基（N、Boc- Na-Fmoc- lysinyl)、Να -苯甲基氧幾基 _ Νε- (9-芴）甲氧基-溶氨 lysinyl)、Νε-第三丁氧羰-Ν«- ( 9-芴）甲氧基-溶氨基酸基（N、Boc- Na-Fmoc-lysinyl)、Να-第三丁氧幾_ ν 苯甲基氧羰基-蛋白氨Νε-bis (9- 芴) methoxy-soluble amino acid group (Nα, N, diFmoc_lysinyl), N- (9-Glu) methoxy-protein amino acid group (N_Fmoc_argininyl), N 'NgUanmnyi_ Di (9 1 芴) methoxy_ protein amino acid group (N 'Ng_idinyLdiFmoc_argininyi), n_ & 芴) methoxy-tissue amino acid group () ^ 邛 111〇 (^ 11 丨 to 丨〇1 丨 1 ^ 1), 1 ^ -Second butoxyl-Nε-benzyloxycarbonyl-amino acid-soluble group (Na-] BOC-Nε_Cbz_lySinyl), NL third butoxycarbonyl_N, benzyloxycarbonyl -Amino-soluble amino group (Nε-β oc-Ν α-C bz-1 ysiny 1), Ν α -third butoxyl _ Νε- (9-芴) methoxy-soluble amino acid group (n «_b 〇c- N ^ Fm〇c-lysinyl), Nε-third butoxycarbonyl- (9-fluorene) methoxy-lysinyl group (N, Boc-Na-Fmoc-lysinyl), Nα-benzyloxy Amino_Nε- (9- 芴) methoxy-amino-soluble lysinyl), Νε-third butoxycarbonyl-N «-(9- 芴) methoxy-soluble amino acid group (N, Boc- Na-Fmoc -lysinyl), Να-tertiary butoxy table_ ν benzyloxycarbonyl-protein ammonia

Cbz- argininyl)、N脈基-第三丁氧羰-Να-苯甲基氧羰基- 蛋白氨基酸基（Nguanidinyl-B〇C- N«_ Cbz_ &^11111^1)、1^-第三丁氧羰->^基-(9-芴）甲氧基_蛋白氨基酸基（Na-Boc- Nguanidinyi-Fm〇C- argininyl)、 N^ -第三丁氧羰-Να- ( 9-芴）甲氧基-蛋白氨基酸基 (Nguanidlnyl-Boc- Na-Fmoc- argininyl)、Να-苯甲基氧羰基-Ν^- (9-芴）甲氧基-蛋白氨基酸基（Να_ cbz-Nguanidlnyl_Fm〇c_ argininyl)、Ne_ 苯甲基氧羰基 _ n脈 (9-苟）甲氧基-蛋白氨基酸基（Νε_ Cbz-Nguanidiny1· 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297这釐） (請先閱讀背面之注意事項再填寫本頁) · --線· 經濟部智慧財產局員工消費合作社印製 591006 A7B7 5 car 年 a 五、發明說明（// ) --Cbz- argininyl), N-Phosyl-Third-butoxycarbonyl-Nα-benzyloxycarbonyl-Protein amino acid (Nguanidinyl-B〇C- N «_ Cbz_ & ^ 11111 ^ 1), 1 ^ -Third Butoxycarbonyl- > ^-(9-fluorene) methoxy-protein amino acid group (Na-Boc- Nguanidinyi-Fmoc-argininyl), N ^ -third butoxycarbonyl-Nα- (9- 芴) Methoxy-protein amino acid group (Nguanidlnyl-Boc- Na-Fmoc- argininyl), Nα-benzyloxycarbonyl-N ^-(9- 芴) methoxy-protein amino acid group (Nα_ cbz-Nguanidlnyl_Fm〇c_ argininyl), Ne_ benzyloxycarbonyl_ n-vein (9-Go) methoxy-protein amino acid group (Nε_ Cbz-Nguanidiny1 · This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 this cent)) Please read the notes on the back before filling in this page) ·-· Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 591006 A7B7 5 car year a 5. Description of the invention (//)-

Fmoc- argininyl)、Na -第三丁氧羰-N脈基N胍基-硝基_ 蛋白氨基酸基（Na- Boc -Nguanidinyl-nitr〇. argininyl)、Na-苯甲基氧羰基-Ν〃-硝基-蛋白氨基酸基（Na- Cbz _ Nguanidinyl -nitro- argininyl)或 (9-芴）甲氧基-N胍基-硝基-蛋白氨基酸基（Na-Fmoc-Fmoc-argininyl), Na-Third-butoxycarbonyl-N pulse group Nguanyl-nitro_ protein amino acid group (Na-Boc-Nguanidinyl-nitr. Argininyl), Na-benzyloxycarbonyl-N〃- Nitro-protein amino acid group (Na-Cbz_Nguanidinyl-nitro-argininyl) or (9- 芴) methoxy-Nguanidyl-nitro-protein amino acid group (Na-Fmoc-

Nguanidinyl -nitro- argininyl)或其藥學上可接受之鹽類；R8或R8’較佳為相同之基團。本發明之式（I )之化合物更佳可為1，4-二{ { 2-〔（Να-第三丁氧羰-Νε-苯甲基氧羰基-溶氨基酸基）胺基〕乙基}胺基} -9，10-蒽醌（l，4-bis { {2-〔（Να -Boc- Νε- Cbz-lysiny 1 ) amino〕ethyl } amino }-9，10-anthracenedione)、1，4-二{ {2-〔（N-第三丁氧羰-甲硫氨基酸基）胺基〕乙基}胺基} -9,10-蒽醌 (1，4-bis { {2_〔（N- Boc-methioninyl) amino〕 ethyl } amino } -9,1 O-anthracenedione) 、1,4-二 { { 2-〔（ N-第三丁氧羰-普林基）胺基〕乙基}胺基} -9，10-蒽醌（l，4_bis { {2-〔（ N- Boc-proliny 1 ) amino〕ethyl } amino } -9,1 O-anthracenedione)、 1，4-二{{2-〔（洛氣基酸基）胺基〕乙基}胺基}· 9，10-蒽醌（l，4-bis { { 2-〔（ lysinyl ) amino〕 ethyl } amino } -9,1 O-anthracenedione) 、1，4-二 { {2-〔（甲硫氨基酸基）胺基〕乙基}胺基} -9，10-蒽酿（l，4-bis { {2-〔（ methioninyl ) amino〕ethyl} amino} -9，10-anthracenedione)以及其藥學上可接受本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297治釐） (請先閱讀背面之注意事項再填寫本頁) - 訂---------線. 經濟部智慧財產局員工消費合作社印製 591006 A7Nguanidinyl-nitro-argininyl) or a pharmaceutically acceptable salt thereof; R8 or R8 'is preferably the same group. The compound of formula (I) of the present invention is more preferably 1,4-bis {{2-[(Nα-third butoxycarbonyl-Nε-benzyloxycarbonyl-amino acid-soluble amino group) ethyl} Amine} -9,10-anthraquinone (l, 4-bis {{2- [(Να -Boc- Νε- Cbz-lysiny 1) amino] ethyl} amino} -9,10-anthracenedione), 1,4 -Bis {{2-[((N-third butoxycarbonyl-methylthioamino) amino] ethyl} amino}}-9,10-anthraquinone (1,4-bis {{2_ [(N- Boc-methioninyl) amino] ethyl} amino} -9,1 O-anthracenedione), 1,4-bis {{2- [((N-third butoxycarbonyl-prinyl) amino] ethyl] amino} amino } -9,10-anthraquinone (l, 4_bis {{2-[(N- Boc-proliny 1) amino] ethyl} amino} -9,1 O-anthracenedione), 1,4-bis {{2- [ (Crystalloyl) amino] ethyl} amino} 9,10-anthraquinone (l, 4-bis {{2- [(lysinyl) amino] ethyl} amino} -9,1 O-anthracenedione ), 1,4-bis {{2-[(methylthioamino group) amino] ethyl} amino} -9,10-anthracene (l, 4-bis {{2- [(methioninyl) amino] ethyl} amino} -9, 10-anthracenedione) and its medicines The paper size is acceptable for China National Standard (CNS) A4 specification (210 X 297 rule) (Please read the notes on the back before filling this page)-Order --------- line. Ministry of Economic Affairs Printed by the Intellectual Property Bureau Employee Consumer Cooperative 591006 A7

五、發明說明（/三：之鹽類、1，4 - r ———補充:蒼I禾基丁基〕乙基}胺V. Description of the invention (/ three: salts, 1,4-r ——— supplement: cumene, butyl) ethyl} amine

〇 HN——(CH2)n—NH2 R1 〇 HN. 基} -9，10 -蒽 i^(i，4-bis { {2-〔（prolinyl) amino〕 ethyl} amino} -9,10-anthracenedione)或前述諸化合物其藥學上可接受之鹽類。本發明之醫療上有效劑量式（I )之化合物可更包括一醫藥上可接受載體組成一種抑制癌細胞活性之醫藥組成物，醫藥上可接受載體可為任何熟悉此項技藝者所習用之醫藥上可接受載體。本發明之式（I)之化合物之合成方法可約略依照如下合成圖所示之方法合成： (ch2)—nh2 ^ (IV) (請先閱讀背面之注意事項再填寫本頁) NRj^'-CR^j'-COOH NR^-CR^-COOH R 式（Yl) 經濟部智慧財產局員工消費合作往印裂〇HN —— (CH2) n—NH2 R1 〇HN. Group} -9,10 -anthracene i ^ (i, 4-bis {{2-[(prolinyl) amino] ethyl} amino} -9,10-anthracenedione ) Or a pharmaceutically acceptable salt of the aforementioned compounds. The medically effective dose of the compound of formula (I) of the present invention may further include a pharmaceutically acceptable carrier to form a pharmaceutical composition that inhibits the activity of cancer cells, and the pharmaceutically acceptable carrier may be any medicine used by those skilled in the art Acceptable carrier. The method for synthesizing the compound of formula (I) of the present invention can be roughly synthesized according to the method shown in the following synthesis diagram: (ch2) —nh2 ^ (IV) (Please read the precautions on the back before filling this page) NRj ^ '- CR ^ j'-COOH NR ^ -CR ^ -COOH R-type (Yl) Consumption cooperation among employees of the Intellectual Property Bureau of the Ministry of Economic Affairs has been broken.

0 HN—(CH2)n- DCC，HOPI，DMF0 HN— (CH2) n- DCC, HOPI, DMF

HN—(CHj)^—N—C—C—R2· 〇 N—R3' l式（經濟部智慧財產局員工消費合作社印製 591006 A7 B7HN— (CHj) ^ — N—C—C—R2 · 〇 N—R3 'l (printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 591006 A7 B7

其中 n、R、R，、Rl、Rl’、 R2、R2，、R3、R3，、R4 以及r4，之定義同前所述。根據以上合成圖所示，相對應之具保護基之酿胺式（VI )化合物係由式（IV )化合物以任何使用於胜肽（P e P t1 d e)合成方法中已經習用廣知之適當之偶合劑（coupling agent)與具有適當保護基之.保護氨基酸縮合而成。而去保護之相對應醯胺式（V )化合物乃由式（I )化合物與於〉谷劑中之強路易士酸（L e w i s acid)進行去保護反應以製備。較佳之縮合反應溫度為30 〇C -70。(：，且縮合反應較佳於氮氣中進行。較佳之偶合劑（coupling agent)諸如N，N’-二異丙基碳化二亞胺 (N，N’-diisopropyl-carbodiimide)、N，N’ -二環己基碳化二亞胺（N，N’-dicyclohexyl carbodiimide)、乙基氯化甲酸（ethyl chloro- formate)、碳化二咪唑（carb〇ny d i i m i d a ζ ο 1 e)或於溶劑中之E C DI。較佳之溶劑為氯化甲院 ( chloro-methane ) 、二氯甲燒 (dichloromethane) 、 1，2-氯化乙燒（1，2- chloroethane) 、 1,1,1-三氣乙烷（1，1，1- trichloroethane)、氯化苯（chlorobenzene)、四氫呋喃 (tetrahydrofurane) 、 1，4-二氧陸圜（l，4-dioxane)、本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297必爱） — — — — — — — — — — — ------11 ^------- — -^» (請先閱讀背面之注意事項再填寫本頁) 591006 年 ----—--，imJu- 五、發明說明（/+) 1，3- — 氧陸圜（1，3 - d i o x an e) 、 1，3 - d i o x a 1 an e 、 (請先閱讀背面之注意事項再填寫本頁) °^§1>^6、1，3-二甲氧乙垸（1，3-(1111^1;11〇乂)^1:11&116)、甲丰（toluene)、苯（benzene)、（xylene)、N，N_ 二甲基甲醯胺（]^，1^-(1111161：11；/1[01*11131111(16)、1<[，]^-二甲基乙酿胺 (N5N-dimethyl acetamide)、乙酸乙酉旨（ethyl acetate)、一乙基亞石風（diethylsulfoxide)、石風（sulfone) 或其混合物。較佳之具有適當保護基之N-保護氨基酸諸如 N-第三丁氧羰普林氨基酸（N-Boc-proline)、N -第三丁氧缓甲硫氨基酸（N-Boc- methione)、N -第三丁氧疑色氨基酸（N-Boc- tryptophan)、N_第三丁氧羰絲氨基酸 (N-Boc_serine)、N-第三丁氧羰異絲氨基酸（N-Boc-threonine)、N-第三丁氧羰半胱氨基酸（N-Boc-cysteine)、N-第三丁氧羰膠氨基醯胺（N-Boc-glutamine)、Να-第三丁氧羰-膠氨基酸（n'Boc-glutamic acid)、N-第三丁氧羰酪氨基酸基（N-Boc-tyrosine)、N-第三丁氧羰天冬氨基醯胺（N-Boc- asparagine)、N_第三丁氧羰-天冬氨基酸（N_Boc-aspartic acid)、Na，Νε二第三丁氧羰溶氨基酸（N«，經濟部智慧財產局員工消費合作社印製 N、diBoc-lysine)、N -第三丁氧羰蛋白氨基酸（N-Boc-arginine)、N-第三丁氧羰組織氨基酸（N-Boc-jiistidine) 、 N- 苯甲基氧羰基 -普林氨基酸（N_Cbz-proline)、N-苯甲基氧羰基-甲硫氨基酸（N-Cbz-methione)、N-苯甲基氧羰基·色氨基酸（N-Cbz-tryptophan)、N-苯甲基氧羰基-絲氨基酸（N-Cbz- 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297込釐） 591006Wherein n, R, R ,, Rl, Rl ', R2, R2, R3, R3, R4, and r4 have the same definitions as described above. According to the above synthetic diagram, the corresponding protective amine-type compound (VI) is a compound of formula (IV) which is widely used in peptide synthesis (P e P t1 de). Coupling agent (coupling agent) with the appropriate protective group. Protected amino acid condensation. The corresponding deprotected amidine (V) compound is prepared by deprotecting a compound of formula (I) with a strong Lewis acid (L e w i s acid) in a cereal. The preferred condensation reaction temperature is 30 ° C-70. (:, And the condensation reaction is preferably performed in nitrogen. A preferred coupling agent such as N, N'-diisopropyl-carbodiimide, N, N ' -Dicyclohexylcarbodiimide (N, N'-dicyclohexyl carbodiimide), ethyl chloro-formate, carbodiyimidazole (Carbony diimida ζ ο 1 e) or EC DI in a solvent The preferred solvents are chloro-methane, dichloromethane, 1,2-chloroethane, 1,1,1-trifluoroethane ( (1,1,1-trichloroethane), chlorobenzene, tetrahydrofurane, 1,4-dioxane, This paper standard is applicable to China National Standard (CNS) A4 specifications ( 210 X 297 must love) — — — — — — — — — — — ------ 11 ^ ------- —-^ »(Please read the notes on the back before filling this page) 591006 Years ----------, imJu- V. Description of the Invention (/ +) 1,3- — Oxyhydrazone (1,3-diox an e), 1,3-dioxa 1 an e, ( Read the notes on the back before filling this page) ° ^ §1 > ^ 6, 1,3-Dimethoxyacetamidine (1,3- (1111 ^ 1; 11〇乂) ^ 1: 11 & 116), Toluene, benzene, (xylene), N, N_dimethylformamide () ^, 1 ^-(1111161: 11; / 1 [01 * 11131111 (16), 1 < [, ] ^-N5N-dimethyl acetamide, ethyl acetate, diethylsulfoxide, sulfone, or a mixture thereof. It is preferred to have a suitable protecting group N-protected amino acids such as N-Boc-proline, N-Boc-methione, N-Boc-prothio (N-Boc-tryptophan), N-Boc-serine, N-Boc-threonine, N-Boc-threonine, N-Boc-threonine Amino acid (N-Boc-cysteine), N-Boc-glutamine, N-Boc-glutamic acid, N-Boc-glutamic acid, N-Boc N-Boc-tyrosine, N-Boc-tyrosine (N-Boc-asparagine), N_Boc-aspartic acid, Na, Νε-second-butoxycarbonyl-soluble amino acid (N «, printed by the Consumers’ Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs N, diBoc-lysine), N-Boc-arginine, N-Boc-jiistidine, N-benzyloxycarbonyl- Purine Amino Acid (N_Cbz-proline), N-Cetyloxycarbonyl-methione, N-Cbz-tryptophan, N-Benzyl Oxycarbonyl-serine amino acid (N-Cbz- This paper size applies to China National Standard (CNS) A4 specification (210 X 297%) 591006

經濟部智慧財產局員工消費合作社印製五、發明說明（/5) serine) 、N-苯甲某氛幽# m ^ ^ J^碳基-異絲氣基酸（N-Cbz- threonine)、N-苯甲基氧羰基_半胱氨基酸（N_cbz_ cysteine)、N-苯甲基氧羰基_膠氨基醯胺（N_cbz_ glUtamine)、笨甲基氧羰基-膠氨基酸（N«-Cbz-giutamic acid)、N-苯甲基氧羰基-酷氨基酸基（N_cbz_ tyr〇Sine)、N_苯甲基氧羰基_天冬氨基醯胺（N-Cbz-asparagine)、N-苯甲基氧羰基…天冬氨基酸⑺彳心· aSpaFtiC aeid)、N' 二苯甲基氧羰基-溶氨基酸（Ν' N^diCbzdysine)、Ν_苯甲基氧羰基-蛋白氨基酸（ν_ CbZ_arginine)、&苯甲基氧羰基-組織氨基酸（N-Cbz-histidine) 、 Ν- ( 9- 苟）甲氧基-普林氨基酸⑺邛㈤^ proline)、N- ( 9-芴）甲氧基-甲硫氨基酸（N- Fmoc-methione) 、 N- (9_ 芴）甲氧基-色氨基酸（N-Fmoc-tryptophan)、N_ ( 9-苟）甲氧基·絲氨基酸…-?.^ serine)、N- ( 9-苗）甲氧基-異絲氨基酸（N- Fmoc-threonine) 、 N- ( 9-芴）甲氧基-半胱氨基酸⑺-?^^ cysteine)、N- ( 9-芴）甲氧基-膠氨基醯胺（N- Fmoc一 glutamine)、Να- ( 9-芴）甲氧基-膠氨基酸（N«_ Fm0C- glUtamicacid)、N-(9-芴）甲氧基·酪氨基酸基（N-Fmo c-tyrosine )、Ν- ( 9 -芴）甲氧基-天冬氨基醯胺（N-Fmoc-asparagine)、N-(9-芴）甲氧基-天冬氨基酸（N-Fmoc-aspartic acid)、Na，Νε-二（9-芴）甲氧基-溶氨基酸（Na，Ne-diFmoc-lysine)、N- (9-芴）甲氧基-蛋白氨基酸（N-Fmoc-arginine)或N- (9-芴）甲氧基-組織氨本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297 β釐） (請先閱讀背面之注意事項再填寫本頁) 訂·- 線· 591006 A7 B7Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs. 5. Description of the Invention (/ 5) serine), N-Benzene, a certain atmosphere. # M ^ ^ J ^ Carbon-iso-threonine, N-benzyloxycarbonyl_cysteine, N-cbz_glUtamine, N «-Cbz-giutamic acid , N-benzyloxycarbonyl- cool amino group (N_cbz_ tyrosine), N_benzyloxycarbonyl_aspartylamine (N-Cbz-asparagine), N-benzyloxycarbonyl ... asparagus Amino acid heart · aSpaFtiC aeid), N 'diphenylmethyloxycarbonyl-soluble amino acid (N' N ^ diCbzdysine), N_benzyloxycarbonyl-protein amino acid (ν_CbZ_arginine), & benzyloxycarbonyl -Tissue amino acid (N-Cbz-histidine), Ν- (9-) methoxy-Pure amino acid (^ proline), N- (9- 芴) methoxy-methylthio amino acid (N- Fmoc -methione), N- (9_ 芴) methoxy-color amino acid (N-Fmoc-tryptophan), N_ (9-go) methoxy · silk amino acid ...-?. ^ serine), N- (9- 苗) Methoxy-isose amino acid (N- Fmoc- threonine), N- (9- 芴) methoxy-cysteine amino acid ⑺-? ^^ cysteine), N- (9- 芴) methoxy-glycinamine (N-Fmoc-glutamine), Nα- (9- 芴) methoxy-glycine amino acid (N «_ Fm0C- glUtamicacid), N- (9- 芴) methoxy · tyrosine amino group (N-Fmo c-tyrosine), Ν- (9-芴) N-Fmoc-asparagine, N- (9- 芴) N-Fmoc-aspartic acid, Na, Nε-bis (9- 芴) Methoxy-soluble amino acid (Na, Ne-diFmoc-lysine), N- (9- 芴) methoxy-protein amino acid (N-Fmoc-arginine) or N- (9- 芴) methoxy-histamine This paper size is in accordance with Chinese National Standard (CNS) A4 (210 X 297 β centimeters) (Please read the precautions on the back before filling out this page) Order ·-thread · 591006 A7 B7

五、發明說明（A ) (請先閱讀背面之注意事項再填寫本頁) ;線· 基酸（>^邛11100-11丨31丨(1丨116)。較佳之去保護反應溫度為3〇。C - 7 0。C，且縮合反應較佳於氮氣中進行。較佳之去保護反應用之路易士酸為氟化氫（hydrogen fluoride)、氯化氫（hydrogen chloride)、溴化氫（hydrogen bromide)、硫酸（sulfuric acid)、甲烷磺酸 (methanesulfonic acid)、苯磺酸（benzene sulfonic acid)、甲苯績酸（toluene sulfonic anid)、三氟錯酸 (trifluoroacetic acid)、三氟甲烷磺酸（trifluoro-methanesulfonic acid) 、三氟化硼(boron trifluoride)、三氯化硼（boron trichloride)、三溴化硼（boron tribromide)、三氯化鋁（aluminum trichloride)、四氯化欽（titanium tetrachloride)或四氣化錯（zirconium tetrachloride)。而較佳之路易士酸溶劑為氯化甲燒（chloro-methane )、二氯甲垸 (dichloromethane) 、 1，2-氯化乙貌（l，2-chloro- 經濟部智慧財產局員工消費合作f£印製 ethane)、1，1，1 -三氯乙燒（1，1，1-trichloro-ethane)、氯化苯（chlorobenzene)、四氫吱喃（tetrahydro-furane)、1，4 -二氧陸圜（l，4-dioxane)、1，3 -二氧陸園 (1，3 - d i ο X an e)、1，3-dioxalane、diglyme、1，3-二甲氧乙燒（1，3-dimethoxy ethane)、甲苯（to 1 u ene)、苯 (benzene)、（xylene)、N，N-二甲基甲醯胺（N，N-dimethylformamide) 、N，N-二甲基乙醯胺（N，N-dimethylacetamide)、乙酸乙酉旨（ethyl acetate)、二乙基亞域（diethylsulfoxide)、>5 風（sulfone)或其混合物。本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297迩釐） 591006 ΙΓ^. U補系五、發明說明（々） u--— 為能能更瞭解本發明之技術内容，特舉新穎胺基醯基蒽醌化合物較佳具體實施例説明如下。 (請先閱讀背面之注意事項再填寫本頁) 貫施例一 1，4 -二{ {2-〔（Να-第三丁氧幾-Νε -苯甲基氧凝基-溶氨基酸基）胺基〕乙基}胺基}_ 9，1 0 -蒽酿之合成，（l，4-bis { { 2- 〔 ( Να- Boc- Νε- Cbz-lysinyl ) amino 〕 ethyl } amino } -9，l〇-anthracenedione) 將4.18克（11 mMole) Na -第三丁氧羰-Νε_苯甲基氧疑基-溶氨基酸（Na-Boc- Νε- Cbz- lysine)、1.96 克 (12 mMole ) N-羥基酞亞胺（N-hydroxyphthalimide) 及2.3克（11.5 mMole) N，N’ -二環己基碳化二亞胺 (N，N’-dicyclohexyl carbodiimide)溶於二氯甲烷（200 經濟部智慧財產局員工消費合作钍印製 m 1)並於室溫揽拌1小時。而後產生之n，N，-二環己基脉白色晶體（N，N ’ - d i c y c 1 〇 h e X y 1 u r e a)以過濾法除去。所得之濾、液再加入1.62克（12 mMole) 1，4-二（β -胺基乙基月；基）-9,10-葱酿一嗣（l，4_bis ( β-aminoethyl-amino ) -9，10-anthracenedione)並於室溫攪拌 20 小時，並以減壓方式移除溶劑。殘餘物以管柱層析法 (silica gel; CHCl3/MeOH )純化，而後粗產物懸浮於氯仿中並以超音波震盪1小時。將此氣仿懸浮液過濾得 3 · 4 5克（產率6 6 % )深藍色晶體，融點1 8 6 - 1 8 7。C。 NMR ( 400 MHz，DMSO-d6 ) : cM.34(s，18H， rt_Bu)，1.55(m，4H，Lysp-CH2)，2.91(m，4H，-CH2NHCO-)，3.51(m，4H，ArNH-CH2-)，3.86(m，本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297 00¾) 經濟部智慧財產局員工消費合作社印製 591006V. Description of the Invention (A) (Please read the precautions on the back before filling this page); Line · Basic Acid (> ^ 邛 11100-11 丨 31 丨 (1 丨 116). The best deprotection reaction temperature is 3 0-C-70, and the condensation reaction is preferably carried out in nitrogen. The preferred Lewis acid for deprotection reaction is hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen bromide, Sulfuric acid, methanesulfonic acid, benzene sulfonic acid, toluene sulfonic anid, trifluoroacetic acid, trifluoro-methanesulfonic acid), boron trifluoride, boron trichloride, boron tribromide, aluminum trichloride, titanium tetrachloride or tetragas Zirconium tetrachloride. The preferred Lewis acid solvents are chloro-methane, dichloromethane, and 1,2-chloroethane. Intellectual Property Agency Industry and consumer cooperation f £ printed ethane), 1,1,1-trichloro-ethane, chlorobenzene, tetrahydro-furane, 1 1,4-dioxane, 1,3-dioxane, 1,3-dioxal, 1,3-dioxalane, diglyme, 1,3-dimethoxy 1,3-dimethoxy ethane, toluene (to 1 u ene), benzene (xylene), N, N-dimethylformamide (N, N-dimethylformamide), N, N- N, N-dimethylacetamide, ethyl acetate, diethylsulfoxide, > 5 sulfone or mixtures thereof. The paper size applies to Chinese national standards ( CNS) A4 specification (210 X 297 mm) 591006 ΙΓ ^. U Supplement V. Description of the invention (々) u ------ In order to better understand the technical content of the present invention, the novel amino fluorenyl anthraquinone compounds are specifically mentioned The preferred embodiments are described below. (Please read the precautions on the back before filling out this page) Example 1 1,4-Di {{2-[(Nα-Third-butoxy-Nε-Benzyloxycoagulation-soluble amino acid-based) amine Group] ethyl} amino} -9,1 0-Synthesis of anthracene, (l, 4-bis {{2- [(Να- Boc- Νε- Cbz-lysinyl) amino] ethyl} amino} -9, l〇-anthracenedione) 4.18 g (11 mMole) of Na-third butoxycarbonyl-Nε-benzyloxy-lysine-soluble amino acid (Na-Boc- Νε- Cbz-lysine), 1.96 g (12 mMole) N -N-hydroxyphthalimide and 2.3 g (11.5 mMole) N, N'-dicyclohexylcarbodiimide (N, N'-dicyclohexyl carbodiimide) dissolved in dichloromethane (200 Intellectual Property Office, Ministry of Economy Employees cooperated to print m 1) and stirred for 1 hour at room temperature. Then, the n, N, -dicyclohexyl vein white crystals (N, N'-d i c y c 1 0 h e X y 1 u r e a) were removed by filtration. The resulting filtrate and liquid was further added with 1.62 g (12 mMole) of 1,4-bis (β-aminoethylammonium) group, 9,10-scallion, and 嗣 (l, 4_bis (β-aminoethyl-amino)- 9,10-anthracenedione) and stirred at room temperature for 20 hours, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (silica gel; CHCl3 / MeOH), and then the crude product was suspended in chloroform and subjected to ultrasonic shock for 1 hour. This aerosol-like suspension was filtered to obtain 3.45 g (66% yield) of dark blue crystals with a melting point of 1 8-1 8 7. C. NMR (400 MHz, DMSO-d6): cM.34 (s, 18H, rt_Bu), 1.55 (m, 4H, Lysp-CH2), 2.91 (m, 4H, -CH2NHCO-), 3.51 (m, 4H, ArNH -CH2-), 3.86 (m, this paper size applies to China National Standard (CNS) A4 (210 X 297 00¾) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 591006

五、發明說明（/5 ) 2H，Lys α-CH)，4.98(m，4H，PhCH2-)，6.70(d，2H， J = 1 0 _ 1 Η z，N Η B o c)，7 · 1 4 (t，2 Η，J = 5 · 8 Η z， NHCbz)，7.31(m，10H，Ph-)，7.56(s，2H，2,3-Ar-H)，7.55(q，2H，J = 4.5 Hz，6,7-Ar-H)，8.04(s，2H，V. Description of the invention (/ 5) 2H, Lys α-CH), 4.98 (m, 4H, PhCH2-), 6.70 (d, 2H, J = 1 0 _ 1 Η z, N Η B oc), 7 · 1 4 (t, 2 Η, J = 5 · 8 Η z, NHCbz), 7.31 (m, 10H, Ph-), 7.56 (s, 2H, 2, 3-Ar-H), 7.55 (q, 2H, J = 4.5 Hz, 6,7-Ar-H), 8.04 (s, 2H,

J = 5.6 Hz， -CH2NHCO-)，8.21(q，2H，J = 5.6 Hz， 5,8-Ar-H)，10.78(t，2H，J = 6 Hz，Ar-NHCH2-)，元素分析·计鼻 C56H72N8O12 · C64.1 ; Η 6.9 2 I Ν10.68，實測C63.7 ; Η6.8 1 ; Ν10.65。實施例二1，4 -二{{ 2 -〔（ Ν -第三丁氧羰-甲硫氨基酸基）胺基〕乙基}胺基} -9，10 -蒽醌之合成；（1，4-bis { { 2-〔（ N- B oc-methioniny 1 ) amino ] ethyl } amino } -9，10-anthracenedione) 本化合物之合成方法及試劑除以2.7 4克（1 1 mMole) N-第三丁氧談-甲硫氨基酸（N- Boc-methionine)代替Να-第三丁氧羰-Νε-苯甲基氧羰基-溶氨基酸（Να-Boc- Ns- Cbz- lysine)外，皆與實施例一相同。得2 · 5 3克（產率6 4 % )晶體，融點2 3 7。C。 NMR (400 MHz，pyridine-d5) : di.46(s，18H， t-Bu)，1.94(s，6H，-SCH3)，2.32(m，4H，Met β-CH2) ，2.51(m，4H，Metr-CH2)，3.68(m，4H，Ar-NHCH2-)，3.77(m，4H，-CH2NHCO-)，4.88(m，4H， Met a -CH)，7.48(s，2H，2,3-Ar-H)，7.68(q，2H， J = 3.2 Hz，6,7-Ar-H) ，8 · 19(d，2H，J = 8 Hz， _ -- _ 21_- —_ 本紙張尺度適用中國國家標準（CNS)A4規格（210 x 297公爱） (請先閱讀背面之注意事項再填寫本頁)J = 5.6 Hz, -CH2NHCO-), 8.21 (q, 2H, J = 5.6 Hz, 5,8-Ar-H), 10.78 (t, 2H, J = 6 Hz, Ar-NHCH2-), elemental analysis · Nose C56H72N8O12 · C64.1; Η 6.9 2 I Ν10.68, found C63.7; Η6.8 1; Ν10.65. Example II Synthesis of 1,4-di {{2-[(Ν -third butoxycarbonyl-methylthioamino) amino] ethyl} amino} -9,10 -anthraquinone; (1,4 -bis {{2- [(N-B oc-methioniny 1) amino] ethyl} amino} -9,10-anthracenedione) Divided by 2.74 g (1 1 mMole) N-third Except for butoxy-methylthio amino acid (N-Boc-methionine) instead of Nα-third butoxycarbonyl-Nε-benzyloxycarbonyl-soluble amino acid (Nα-Boc- Ns- Cbz- lysine), it is the same as the example One is the same. 2.53 g (64% yield) crystals were obtained, with a melting point of 2 37. C. NMR (400 MHz, pyridine-d5): di.46 (s, 18H, t-Bu), 1.94 (s, 6H, -SCH3), 2.32 (m, 4H, Met β-CH2), 2.51 (m, 4H , Metr-CH2), 3.68 (m, 4H, Ar-NHCH2-), 3.77 (m, 4H, -CH2NHCO-), 4.88 (m, 4H, Met a -CH), 7.48 (s, 2H, 2, 3 -Ar-H), 7.68 (q, 2H, J = 3.2 Hz, 6,7-Ar-H), 8 · 19 (d, 2H, J = 8 Hz, _-_ 21_- --_ This paper size Applicable to China National Standard (CNS) A4 specification (210 x 297 public love) (Please read the precautions on the back before filling this page)

經濟部智慧財產局員工消費合作社印製 591006 A7 ________ 五、發明說明（w) I氣’^_充 NHBoc)，8.58 (q，2H，] = Τ7Τ~ίΓζ ^ ^8-Ar-H)， 9.32(s， 2H， -CH2NHCO-) ， 11.21(s， 2H， Ar- NHCH2-)，元素分析：計算 C38H54N6〇8S2 : C5 7.99 ; H6.92 ; N10.68，實測C57.94 ; H6.96 ; N10.44。實施例三 I，4-二{ {2-〔（ N-第三丁氧羰-普林基）胺基〕乙基}胺基}-9，10-蒽醌；（1，4-1^5{{2-〔（>1-Boc-prolinyl ) amino 〕 ethyl } amino } -9，10- anthracenedione) 本化合物之合成方法及試劑除以2.3 7克（1 1 mMole) N-第三丁氧缓-普林基（N- Boc_proline)代替Να-第三丁氧羰-Νε-苯甲基氧羰基-溶氨基酸（Να-Boc- Νε- Cbz- lysine)外，皆與實施例一相同。得2.15 克（產率60% )晶體，融點90。 NMR ( 400 MHz，DMSO_d6 ) : d 1.28(s，18H， Γ t - B u) ， 1 · 7 7 (m， 4 Η， P r o 尸-C Η 2) ， 2.0 7 (m， 4 Η， P r ο P-CH2)，3.27(m，4H，ArNH-CH2-)，3.50(m，4H，-CH2NHC〇-)，4.00(m，4H，Pro 汉-CH)，7.56(s，2H， 2,3-Ar-H)，7.77(q，2H，J = 4 Hz，6,7-Ar-H)，8.10(s， 2H，-CH2NHCO-)，8.58(q，2H，J = 4Hz，5,8-Ar-H)，10.75(s，2H，Ar-NHCH2-)，元素分析：計算 C38H50N6O8 ： C61.49 ； H7.01 ; N11.69 ，實測 C61.92 ; H7.15 ; N1 1.19。本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297 0 ) (請先閱讀背面之注意事項再填寫本頁) -裝--------訂---------線- 591006 A7 B7 五、發明說明（如）實施例四 1，4 - 修正 90. 5. 11補見 { {2-〔（溶氨基酸基）胺基〕乙基} 胺基} -9，10-蒽醌之合成；（l，4-bis { { 2- 〔(lysinyl ) amino ] ethyl } amino } -9，l〇_ anthracenedione) 將 1.3 克（1.23 9 mMole ) 1，4-二{ {2-〔（ Na-第三丁氧羰-Νε-苯甲基氧羰基-溶氨基酸基）胺基〕乙基} 胺基} -9，10_ 蒽醌（l，4-bis{{2-〔（Na-Boc-Nε·^ Cbz-lysinyl ) amino ] ethyl } amino } -9,10- anthracenedione)溶於50 ml氯仿中，而後加入3.4 ml (50 eq )三氟醋酸，並於室溫攪拌4小時。溶劑及三氟醋酸以眞空蒸發除去。將乙醚加入此殘餘物並研磨成粉，旅將清澈之上層液除去。過濾，以乙醚清洗，並於眞空下乾燥得0_52克產物，產率72%。 NMR ( 400 MHz，DMSO-d6 ) : 1·34(ρ，4H， J = 7.6Hz，Lys d -CH2)，1 · 5 1 (p，4H，J = 7 · 6Hz，Ly s r -CH2)，1.71(p，4H，Lys -CH2)，2.75(t，4H， J = 7.6Hz ，ArNHC〇chH2-)，3.36(m，4H，Lys ε -CH2) ，3.59(m，4H，-CH2NHCO-)，3.72(t，4H， J = 6_4 Hz，Lys 汉-CH2)，7.57(s，2H，2,3-Ar-H)， 7.81(q, 2H, J = 3.2 Hz5 6,7-Ar-H) ，8.23(q，2H， J = 3.2 Hz，5,8-Ar-H)，8.76(t，2H5 J = 4.2 Hz,-CH2NHCO-)，10.79(t，2H， J = 6 Hz，Ar-NHCH2·)，元素分析：計算 C3〇H44N804 + 4.5C2 F3 H2 02 : 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297 β釐） -------------------訂--------- (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 591006 A7 B7 修正五、發明說明（2/ ) C42.82 ; H4.46 ; N10.24，實測 C42.83 ; H4.86 ; N9.96 〇實施例五1，4-二（（2-(甲硫氨基酸基）胺基〕乙基}胺基} -9,10-蒽醌之合成；（1，4 - b i s ((2 - (methioninylamino)ethyl)amino)-9，10-anthracenedione) 本化合物之合成方法及試劑除起始物以〇 . 7克 (0.889 mMole) 1，4 -二{ {2-〔（N-第三丁氧緩-甲硫氨基酸基）胺基〕乙基}胺基} - 9，1 0 -蒽職（1，4 - b i s { { 2-〔（ N- Boc-methioninyl ) amino〕ethyl } amino } -9，10-anthracenedione)代替 1，心二{ { 2- 〔（Να-第三丁氧羰-Νε-苯甲基氧羰基-溶氨基酸基）胺基〕乙基}胺基} -9，10-蒽醌（l，4-bis { {2-〔（Να-Printed by the Employees 'Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs 591006 A7 ________ V. Description of the invention (w) I gas' ^ _charge NHBoc), 8.58 (q, 2H,] = Τ7Τ ~ ίΓζ ^ ^ 8-Ar-H), 9.32 (s, 2H, -CH2NHCO-), 11.21 (s, 2H, Ar-NHCH2-), elemental analysis: calculated C38H54N6〇8S2: C5 7.99; H6.92; N10.68, found C57.94; H6.96; N10.44. Example III I, 4-di {{2-[(N-Third-butoxycarbonyl-Prinyl) amino] ethyl} amino} -9,10-anthraquinone; (1,4-1 ^ 5 {{2-[(> 1-Boc-prolinyl) amino] ethyl} amino} -9,10- anthracenedione) Divided by 2.37 g (1 1 mMole) N-Third-butyl The same as the first embodiment except that N-Boc_proline replaced Nα-third butoxycarbonyl-Nε-benzyloxycarbonyl-soluble amino acid (Nα-Boc-Nε-Cbz-lysine). There were obtained 2.15 g (60% yield) of crystals with a melting point of 90. NMR (400 MHz, DMSO_d6): d 1.28 (s, 18H, Γ t-B u), 1 · 7 7 (m, 4 Η, P ro -C Η 2), 2.0 7 (m, 4 Η, P r ο P-CH2), 3.27 (m, 4H, ArNH-CH2-), 3.50 (m, 4H, -CH2NHC0-), 4.00 (m, 4H, Pro Han-CH), 7.56 (s, 2H, 2 , 3-Ar-H), 7.77 (q, 2H, J = 4 Hz, 6,7-Ar-H), 8.10 (s, 2H, -CH2NHCO-), 8.58 (q, 2H, J = 4Hz, 5 , 8-Ar-H), 10.75 (s, 2H, Ar-NHCH2-), elemental analysis: calculated C38H50N6O8: C61.49; H7.01; N11.69, found C61.92; H7.15; N1 1.19. This paper size applies to China National Standard (CNS) A4 specifications (210 X 297 0) (Please read the precautions on the back before filling this page) -Install -------- Order -------- -Line- 591006 A7 B7 V. Description of the invention (eg) Example 4 1, 4-Correction 90. 5. 11 See also {{2-[(soluble amino acid group) amino group] ethyl} amino group} -9, Synthesis of 10-anthraquinone; (l, 4-bis {{2- [(lysinyl) amino] ethyl} amino} -9, l0_ anthracenedione) 1.3 g (1.23 9 mMole) 1,4-bis {{ 2-[(Na-Third-butoxycarbonyl-Nε-benzyloxycarbonyl-amino-soluble amino) amino] ethyl} amino} -9,10_ anthraquinone (l, 4-bis {{2- [ (Na-Boc-Nε · ^ Cbz-lysinyl) amino] ethyl} amino} -9,10- anthracenedione) was dissolved in 50 ml of chloroform, then 3.4 ml (50 eq) of trifluoroacetic acid was added and stirred at room temperature for 4 hour. The solvent and trifluoroacetic acid were removed by vacuum evaporation. Diethyl ether was added to the residue and triturated to a powder, and the clear supernatant was removed. Filtration, washing with diethyl ether, and drying under vacuum gave 0-52 g of product with a yield of 72%. NMR (400 MHz, DMSO-d6): 1.34 (ρ, 4H, J = 7.6Hz, Lys d -CH2), 1 · 5 1 (p, 4H, J = 7 · 6Hz, Ly sr -CH2), 1.71 (p, 4H, Lys-CH2), 2.75 (t, 4H, J = 7.6Hz, ArNHCochch2-), 3.36 (m, 4H, Lys ε-CH2), 3.59 (m, 4H, -CH2NHCO-) , 3.72 (t, 4H, J = 6_4 Hz, Lys Han-CH2), 7.57 (s, 2H, 2, 3-Ar-H), 7.81 (q, 2H, J = 3.2 Hz5 6, 7-Ar-H ), 8.23 (q, 2H, J = 3.2 Hz, 5, 8-Ar-H), 8.76 (t, 2H5 J = 4.2 Hz, -CH2NHCO-), 10.79 (t, 2H, J = 6 Hz, Ar- NHCH2 ·), Elemental analysis: Calculate C3〇H44N804 + 4.5C2 F3 H2 02: This paper size applies to China National Standard (CNS) A4 (210 X 297 β centigrade) ------------- ------ Order --------- (Please read the notes on the back before filling out this page) Printed by the Employees' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 591006 A7 B7 Amendment V. Description of Invention (2 / ) C42.82; H4.46; N10.24, found C42.83; H4.86; N9.96. Example 5 1,4-bis ((2- (methylthioamino) amino) ethyl)} Synthesis of amine} -9,10-anthraquinone; (1,4-bis ((2-(methioninylamino) ethyl) amino) -9 10-anthracenedione) The synthesis method and reagents of the compound except that the starting material is 0.7 g (0.889 mMole) 1,4-di {{2-[(N-third butoxyl-methylthioaminoamino) amine Group] ethyl} amino} -9,1 0 -anthracene (1,4-bis {{2- [(N-Boc-methioninyl) amino] ethyl} amino} -9,10-anthracenedione) instead of 1, Heart di {{2- [((Nα-third butoxycarbonyl-Nε-benzyloxycarbonyl-soluble amino acid group) amino group] ethyl} amino group) -9,10-anthraquinone (l, 4-bis {{2- [(Να-

Boc- Νε- Cbz-lysinyl) amino) ethyl} amino}-9，10-anthracenedione)外，皆與實施例四相同。得0 42 克（產率80%)產物。 NMR (400 MHz，DNSO-d6) : cM.95(s，6H，_ SCH3)，1 .96(m，4H，Met β- CH2) ，2.44(t，4H， J = 4 Hz，Met r -CH2) ，3.59(m， 8H，Ar-NHCH2-)， 3.82(t，2H，J = 6.4 Hz，Met ^-CH)，7.55(s，2H，2,3-Ar-H)，8.24(q，2H，J = 2.4 Hz，5,8-Ar-H)，8.76(s， 2H，-CH2NHCO-)，10.79(s，2H，Ar-NHCH2-)元素分析：計算C38H54N608S2 + 2.4C2 F3 H2 02 : C45.79 ; H4.73 ; N9.77，實測C45.5 5 ; Η5·0 9 ; N9.84 〇本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297备釐） -----------^^^裝--------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印製 591006Except for Boc-Nε-Cbz-lysinyl) amino) ethyl} amino} -9, 10-anthracenedione), it is the same as that of the fourth embodiment. This gave 0 42 g (80% yield) of product. NMR (400 MHz, DNSO-d6): cM.95 (s, 6H, _SCH3), 1.96 (m, 4H, Met β-CH2), 2.44 (t, 4H, J = 4 Hz, Met r- CH2), 3.59 (m, 8H, Ar-NHCH2-), 3.82 (t, 2H, J = 6.4 Hz, Met ^ -CH), 7.55 (s, 2H, 2,3-Ar-H), 8.24 (q , 2H, J = 2.4 Hz, 5,8-Ar-H), 8.76 (s, 2H, -CH2NHCO-), 10.79 (s, 2H, Ar-NHCH2-) Elemental analysis: Calculate C38H54N608S2 + 2.4C2 F3 H2 02 : C45.79; H4.73; N9.77, measured C45.5 5; Η5.09; N9.84 〇 This paper size is applicable to China National Standard (CNS) A4 (210 X 297). --- -------- ^^^ Packing -------- Order --------- line (please read the precautions on the back before filling this page) Staff of Intellectual Property Bureau, Ministry of Economic Affairs Printed by Consumer Cooperative 591006

五、發明說明（汉經濟部智慧財產局員工消費合作钍印贤貫施例六1，4 -二{ { 2 -(普林基）胺基〕乙基}胺基}- 9，1〇-蒽 1¾，（l，4-bis ( ( 2- ( prolinyl ) amino ) ethyl) amino ) -9，10-anthracenedione) 本化合物之合成方法及試劑除起始物以0.8克（丨.i 2 mMole) 1，4-二{ {2-〔（N-第三丁氧羰-普林基）胺基〕乙基}胺基} -9,1 0_ 蒽醌；（1，4-13丨8{{2-〔（]^-Boc-prolinyl ) amino ] ethyl } amino } -9,10- anthracenedione)代替 1，4-二{ {2-〔（Να-第三丁氧羰-Νε-苯甲基氧羰基-溶氨基酸基）胺基〕乙基}胺基} -9，10-蒽醌（l，4-bis { {2-〔（Na- Boc- Νε-V. Description of the Invention (Consumption Cooperation of Employees of the Intellectual Property Bureau of the Ministry of Economic Affairs of the People's Republic of China, Yin Yinxian, Example 6 1,4-Di {{2-(Prime) amino] ethyl} amino} -9,1〇- Anthracene 1¾, (l, 4-bis ((2- (prolinyl) amino) ethyl) amino) -9,10-anthracenedione) The synthesis method and reagents of this compound except that the starting material is 0.8 g (丨 .i 2 mMole) 1,4-bis {{2-[(N-third butoxycarbonyl-prinyl) amino] ethyl} amino} -9,1 0_ anthraquinone; (1,4-13 丨 8 {{ 2-[(] ^-Boc-prolinyl) amino] ethyl} amino} -9,10- anthracenedione) instead of 1,4-bis {{2-[(Να- 三丁丁 carbonyl-Νε-phenylmethyloxy) Carbonyl-amino-soluble amino group) amino] ethyl} amino} -9,10-anthraquinone (l, 4-bis {{2- [(Na- Boc- Νε-

Cbz-lysinyl ) amino 〕 ethyl } amino } -9,10- anthracenedione)外，皆與實施例四相同。得0.44克 (產率76% )產物。 NMR ( 400 MHz，DMSO-d6 ) : d 1.86(m，4H， Pro 卜CH2)，2.25(m，4H，Pro β- CH2) ，3.20(m， 4H，Pro r -CH2)，3.56(m，Ar-NH CH2CH2-)， 4.16(m，4H，Proa-CH)，7.55(s，2H，2,3-Ar-H)， 7.81(q，2H，J = 3.2 Hz，6,7-Ar-H)，8.22 (t，2H， J = 3.2 Hz，5,8-Ar-H)，8.78(s，2H，-CH2NHCO·)， l〇.79(s， 2H， Ar-NHCH2-)，元素分析：計算 C38H50N6O8 + 2.2C2 F3 H2 02 ： C5 0.5 7 ； H4.36 ； N10.75，實測C5 0.8 ; H4.36 ; N10.75 〇實施例七本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297於爱) 裝--------訂---------線· (請先閱讀背面之注意事項再填寫本頁)Cbz-lysinyl) amino] ethyl} amino} -9,10- anthracenedione) is the same as in the fourth embodiment. 0.44 g (76% yield) of product was obtained. NMR (400 MHz, DMSO-d6): d 1.86 (m, 4H, Pro CH2), 2.25 (m, 4H, Pro β-CH2), 3.20 (m, 4H, Pro r-CH2), 3.56 (m, Ar-NH CH2CH2-), 4.16 (m, 4H, Proa-CH), 7.55 (s, 2H, 2,3-Ar-H), 7.81 (q, 2H, J = 3.2 Hz, 6,7-Ar- H), 8.22 (t, 2H, J = 3.2 Hz, 5,8-Ar-H), 8.78 (s, 2H, -CH2NHCO ·), 10.79 (s, 2H, Ar-NHCH2-), element Analysis: Calculate C38H50N6O8 + 2.2C2 F3 H2 02: C5 0.5 7; H4.36; N10.75, measured C5 0.8; H4.36; N10.75 〇 Example 7 This paper size applies the Chinese National Standard (CNS) A4 specification (210 X 297 Yu Ai) installed -------- order --------- line · (Please read the precautions on the back before filling this page)

591006 修正五、發明說明(乃） I.蓋以上所合成藥物依照National Cancer* Institute (N CI)之 Developemental Therapeutics Program Human Tumor Cell Line Screen程序對不同之癌細胞株c e 11 1 i n e進行a n t i v e ο p 1 a s t i c活性測試，其步驟約略如下：稀釋的特殊細胞型態及預期目標細胞（target cell ) 濃度（基於細胞生長特性每孔為5000-4000細胞）之懸浮液以pipet滴管加至96孔之孔洞培養皿 (microtiterplates )。於3 7 〇C下預培養24小時以穩定化，將1 0 0 // 1兩倍於欲測試濃度之稀釋液於時間為〇時加入於孔洞培養皿（microtiterplates)之孔中，通常測試之化合物係以五個1 0倍之稀釋液進行評估，而最高孔中濃度為1 0·4Μ，但是對標準試劑而言最高孔中濃度可取決於試劑。於5 %C〇2下，1〇〇%濕度下持續培養48小時。其後使用sulforhodamine B分析細胞，並以plate reader 讀取其光學密度，再配以電腦計算成濃度參數，結果列於表 -0 裝--------1T---------線· (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員工消費合作社印制代表一化合物 (II)之 Rg = gi50 Να-Β 〇 c -Ν、 Cbz-1 y s i η y 1 1 y s i n y 1 N - Boc-m e t h i ο n iny 1 M e t h i ο n iny I N - Boc-p r ο I i n y I p r ο 1 i n y 1 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297遂爱） 591006591006 Amendment V. Description of the invention (I) I. The drugs synthesized above are covered in accordance with the National Cancer * Institute (N CI) Developemental Therapeutics Program Human Tumor Cell Line Screen program for anti cancer ce 11 1 ine anti ο p 1 astic activity test, the steps are roughly as follows: a suspension of the diluted special cell type and the expected target cell concentration (5000-4000 cells per well based on cell growth characteristics) is added to the 96-well hole with a pipet dropper Microtiterplates. Pre-incubate at 37 ° C for 24 hours to stabilize. Add 1 0 // 1/2 times the concentration to be tested into the wells of microtiter plates at the time of 0, usually tested. Compounds were evaluated using five 10-fold dilutions, with the highest concentration in the wells being 10.4M, but for standard reagents the highest concentration in the wells may depend on the reagent. Incubation was continued at 5% CO2 and 100% humidity for 48 hours. Then use sulforhodamine B to analyze the cells, and read its optical density with a plate reader, and then use the computer to calculate the concentration parameters. The results are listed in Table-0. -------- 1T ------- --Line · (Please read the notes on the back before filling this page) Rg = gi50 Να-Β 〇c-Ν, Cbz-1 ysi η printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs on behalf of a compound (II) y 1 1 ysiny 1 N-Boc-m ethi ο n iny 1 M ethi ο n iny IN-Boc-p r ο I iny I pr ο 1 iny 1 This paper size applies to China National Standard (CNS) A4 (210 X 297 Sui Ai) 591006

經濟部智慧財產局員工消費合作社印製 L e u k e m i a CCRF- 3.31E- 8.86E- 3 .90E- 3 .32E- 〉1 .00E- 1 . 89E- CEM 06 05 06 07 04 05 HL- 1.31E- > 1 .00E- 5.01E- 3 .24E- > 1 .00E- 3 · 10E- 60(TB) 07 04 06 07 04 05 K-562 1 .3 7E- > 1 .00E- 3 .28E- 4.24E- <1 .00E- 1 .93E- 06 04 06 07 08 05 MOLT-4 〉1 . 00E- 5 .3 5E- 2 .3 6E- 7.62E- 9.86E- 2.21E- 04 06 06 08 06 0 5 RPMI- 8.98E- 5.33E- 2.65E- 1 .04E- <1 .00E- 2.26E- 8 2 2 6 0 8 05 06 06 08 05 SR 3 .55E- 5.06E- 2.16E- 1 .51E- 1 .43E- 2.20E- 05 06 06 07 05 05 N ο n - S m a 11 Cell L u n g Can c e r A549/A > 1 .00E- 6.30E- 2.84E- 5 . 80E- 1 .58E- > 1 .00E- TCC 04 05 06 07 05 04 EK VX > 1 .00E- > 1 .00E- 2·18E- 1 ·93Ε- 2.71E- 〉1 .00E- 04 04 06 06 05 04 HOP-62 2.35E- 3.67E- 1 .83 E- 5 . 14E- 1 .54E- 4.50E- 05 06 06 07 05 05 HOP-92 9.95E- 3 · 14E- 1 .87E- 9.36E- 1 .3 8E- 4.10E- 05 06 06 07 05 05 NCI- > 1 .00E- 4.71E- 1 .98E- 7.20E- 1 .85E- > 1 .00E- H226 04 06 06 07 05 04 NCI- 2.54E- 4.33E05 2.67E- 1 .06E- 1 . 5 6E- 5 .29E- H23 05 06 06 05 05 NCI- > 1 .00E- 2.59E- 1 .69E- 8.90E- 1 .60E- < 1 .00E- H 3 2 2 M 04 05 05 07 05 08 NCI- > 1 .00E- 9.07E- 5 . 84E- 3.51E- - - H460 04 06 06 07 NCI- 1 .03E- 3 .56E- 1 .3 9E- 1 .99E- 1 .30E- 1 · 9 9 E - H522 05 06 06 07 05 0 5 Colon Cancer COLO 4. 1 3E- > 1 .00E- 1 .99E- 1 _03E- 1 .44E- 2.45E- --------tT---------線 i^w. (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297奴爱） 591006Printed by Leukemia CCRF- 3.31E- 8.86E- 3 .90E- 3 .32E-〉 1.00E- 1. 89E- CEM 06 05 06 07 04 05 HL- 1.31E- > 1.00E- 5.01E- 3 .24E- > 1 .00E- 3 · 10E- 60 (TB) 07 04 06 07 04 05 K-562 1 .3 7E- > 1 .00E- 3 .28E- 4.24E- < 1 .00E- 1 .93E- 06 04 06 07 08 05 MOLT-4〉 1. 00E- 5 .3 5E- 2 .3 6E- 7.62E- 9.86E- 2.21E- 04 06 06 08 06 0 5 RPMI- 8.98E- 5.33E- 2.65E- 1 .04E- < 1 .00E- 2.26E- 8 2 2 6 0 8 05 06 06 08 05 SR 3 .55E- 5.06E- 2.16E- 1 .51E- 1 .43E- 2.20E- 05 06 06 07 05 05 N ο n-S ma 11 Cell Lung Can cer A549 / A > 1 .00E- 6.30E- 2.84E- 5. 80E- 1 .58E -> 1.00E- TCC 04 05 06 07 05 04 EK VX > 1 .00E- > 1 .00E- 2 · 18E- 1 · 93Ε- 2.71E-〉 1 .00E- 04 04 06 06 05 04 HOP-62 2.35E- 3.67E- 1 .83 E- 5. 14E- 1 .54E- 4.50E- 05 06 06 07 05 05 HOP-92 9.95E- 3 · 14E- 1 .87E- 9.36E- 1. 3 8E- 4.10E- 05 06 06 07 05 05 NCI- > 1 .00E- 4.71E- 1 .98E- 7.20E- 1 .85E- > 1 .00E- H226 0 4 06 06 07 05 04 NCI- 2.54E- 4.33E05 2.67E- 1 .06E- 1. 5 6E- 5 .29E- H23 05 06 06 05 05 NCI- > 1. 00E- 2.59E- 1 .69E- 8.90E- 1 .60E- < 1. 00E- H 3 2 2 M 04 05 05 07 05 08 NCI- > 1 .00E- 9.07E- 5. 84E- 3.51E----H460 04 06 06 07 NCI -1 .03E- 3 .56E- 1 .3 9E- 1 .99E- 1 .30E- 1 · 9 9 E-H522 05 06 06 07 05 0 5 Colon Cancer COLO 4. 1 3E- > 1 .00E- 1 .99E- 1 _03E- 1 .44E- 2.45E- -------- tT --------- line i ^ w. (Please read the precautions on the back before filling this page) This paper size applies to China National Standard (CNS) A4 (210 X 297 Slave) 591006

Λ RΛ R

五、發明說明（2歹）V. Description of the invention (2 歹)

經濟部智慧財產局員工消費合作社印製 205 05 04 06 06 05 05 HCC- 3.15 E- 3 .20E- 1 .52E- 3.81E- 1 .30E- 3 .59E- 299 8 06 05 06 07 05 05 HCT- 6. 1 7E- 3 .29E- 3.13 E- 4.45E- 1 .33E- 2.66E- 116 05 05 05 07 0 5 06 HCT- 1 5 > 1 .OOE- > 1 .00E- > 1 .00E- 2 _21E- 1 .39E- > 1 .00E- 04 04 04 06 05 04 HT29 > 1 .00E- 3.91E- 1 .64E- 5.31E- 1 .3 7E- 4.74E- 04 05 06 07 0 5 05 KM 1 2 1 . 5 7E- > 1 .00E- 4.70E- 5 .79E- 1 .22E- 2 .3 2E- 05 04 06 07 05 05 S W-620 6.75E- 5 .3 7E- 1 . 5 8E- 7.39E- 1 .3 8E- 4.04E- 05 05 06 07 05 05 CNS Can c e r SF-268 1.01E- > 1 .00E- 1 .3 0E- 3 . 5 7E- 3 . 12E- 3.41E- 05 04 06 07 05 05 SF-295 8.77E- > 1 .00E- 3 .45E- 1 .04E- 1 .80E- > 1 .00E- 05 04 06 06 05 04 SF-539 2.47E- 7.68E- 2.02E- 6.8 5 E- 1.61E- 4.45E- 05 06 06 07 05 05 SNB- 1 9 1 .03 E- 1 .3 6E- 1 .94E- 5 .98E- < 1 .00E- 4.40E- 05 05 06 07 08 05 SNB-75 1 . 5 6E- 2.92E- 1 ·33Ε- 1 .32E- 2.04E- 5.33E- 05 05 06 06 05 05 U2 5 1 3 .49E- 5 . 14E- 2.58E- 6.39E- 1 .88E- 3 .72E- 06 05 06 07 0 5 05 LOX 8.24E- 1.01E- 1.31E- 4.79E- 1 .24E- 4.15 E- IM VI 05 05 05 07 05 08 MALME > 1 .00E- > 1 .00E- 1 .57E- 1 .99E- 1 .52E- 9.5 9E- -3 Μ 04 04 06 06 05 05 Μ 1 4 > 1 .00E- > 1 .00E- 2.84E- 3.13 E- 1 .58E- > 1 .00E- 04 04 06 06 05 04 sx- 1 .78E- > 1 .00E- 1 .3 8E- 5.63 E- 2.08E- > 1 .00E- MEL-2 05 04 05 06 05 04 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS)A4規格mo X 297 >28爱）訂---------線-Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 205 05 04 06 06 05 05 HCC- 3.15 E- 3 .20E- 1. .52E- 3.81E- 1. .30E- 3.59E- 299 8 06 05 06 07 05 05 HCT -6. 1 7E- 3 .29E- 3.13 E- 4.45E- 1 .33E- 2.66E- 116 05 05 05 07 0 5 06 HCT- 1 5 > 1 .OOE- > 1 .00E- > 1 .00E- 2 _21E- 1 .39E- > 1 .00E- 04 04 04 06 05 04 HT29 > 1 .00E- 3.91E- 1 .64E- 5.31E- 1 .3 7E- 4.74E- 04 05 06 07 0 5 05 KM 1 2 1.. 5 7E- > 1. 00E- 4.70E- 5 .79E- 1 .22E- 2 .3 2E- 05 04 06 07 05 05 S W-620 6.75E- 5 .3 7E- 1. 5 8E- 7.39E- 1 .3 8E- 4.04E- 05 05 06 07 05 05 CNS Can cer SF-268 1.01E- > 1 .00E- 1 .3 0E- 3. 5 7E- 3 . 12E- 3.41E- 05 04 06 07 05 05 SF-295 8.77E- > 1 .00E- 3 .45E- 1 .04E- 1 .80E- > 1 .00E- 05 04 06 06 05 04 SF- 539 2.47E- 7.68E- 2.02E- 6.8 5 E- 1.61E- 4.45E- 05 06 06 07 05 05 SNB- 1 9 1 .03 E- 1.3 .6E- 1.94E- 5 .98E- < 1.00E- 4.40E- 05 05 06 07 08 05 SNB-75 1. 5 6E- 2.92E- 1 · 33E- 1 .32E- 2.04E- 5.33E- 05 05 06 06 05 05 U2 5 1 3 .49 E- 5. 14E- 2.58E- 6.39E- 1 .88E- 3 .72E- 06 05 06 07 0 5 05 LOX 8.24E- 1.01E- 1.31E- 4.79E- 1 .24E- 4.15 E- IM VI 05 05 05 07 05 08 MALME > 1 .00E- > 1 .00E- 1 .57E- 1 .99E- 1 .52E- 9.5 9E- -3 Μ 04 04 06 06 05 05 Μ 1 4 > 1 .00E -> 1.00E- 2.84E- 3.13 E- 1 .58E- > 1 .00E- 04 04 06 06 05 04 sx- 1 .78E- > 1 .00E- 1 .3 8E- 5.63 E- 2.08 E- > 1. 00E- MEL-2 05 04 05 06 05 04 (Please read the notes on the back before filling in this page) This paper size is applicable to China National Standard (CNS) A4 size mo X 297 > 28 Love) Order --------- line-

591006 五、發明說明（％ ) 經濟部智慧財產局員工消費合作社印製 SK- 1 .47E- > 1 .00E- 1 .44E- 1 .75E- 1 .43 E- 4. 1 7E- MEL-2 8 05 04 06 06 05 05 SK- > 1 .00E- > 1 .00E- 3 .07E- 3 .48E- 1 . 12E- 8.8 5 E- MEL-5 04 04 06 06 07 05 U ACC- > 1 .00E- > 1 .00E- 2.34E- 3.03E- 1 .45E- > 1 .00E- 25 7 04 04 06 06 05 04 U ACC- 8·73 E- > 1 . 00E- 2.52E- 1 . 17E- 1 .16E- 3.87E- 62 06 04 06 06 05 05 Ovarian Cancer IGRO VI 3.83E- > 1 .00E- 1 .90E- 2. 1 5E- 1 .39E- 6.26E- 05 04 06 06 05 05 0 VC AR 6.31E- > 1 · 00E- 2.93E- 2.21E- 1 .41E- 6.99E- -3 05 04 06 06 05 05 0 VC AR > 1 .00E- > 1 .00E- 3 . 1 4E- 1 . 5 7E- 1 . 5 0E- > 1 .00E- -4 04 04 06 06 05 04 0 VC AR > 1 .00E- 5.51E- 2.42E- 1 .42E- 1 .67E- 5 . 1 4E- -5 04 05 06 06 05 0 5 0 VC AR 9.8 8E- 4.29E- 1 .49E- 5 .29E- 5 . 84E- 3 .39E- -8 06 06 06 07 06 05 SK-0V- 2.11E- 2.89E- 3.51E- 1 .92E- 1 .97E*0 > 1 .00E- 3 05 05 03 0 6 5 04 Renal Cancer 7 8 6 -0 > 1 . 00E- 6.92E- 1 .63E- 3 .76E- 1 .48E- 2 . 1 9E- 04 06 05 07 0 5 07 A498 〉1 .00E- 4.65E- 4.62E- 1 .72E- - - 04 05 06 06 ACHN > 1 .00E- 2.89E- 3.5 5 E- 3 .86E- 1 .54E- 5 .3 8E- 04 05 06 07 05 05 C AKI- 1 > 1 .00E- > 1 .00E- 6.31E- 8.21E- 1 . 84E- > 1 .00E- 04 04 06 07 05 04 RXF 2.57E- 9.85E- 1 .63E- 1 .92E- - - 393 05 06 05 06 SN 1 2C > 1 .OOE- 3 . 5 6E- 3 .74E- 2.72E- - 4.60E- 04 06 06 07 05 --------訂---------線 (請先閱讀背面之注意事項再填寫本頁) 本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297 29釐） 591006591006 V. Description of the invention (%) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs SK- 1.47E- > 1.00E- 1.44E- 1.75E- 1.43 E- 4. 1 7E- MEL- 2 8 05 04 06 06 05 05 SK- > 1 .00E- > 1 .00E- 3 .07E- 3 .48E- 1. 12E- 8.8 5 E- MEL-5 04 04 06 06 07 05 U ACC- > 1.00E- > 1.00E- 2.34E- 3.03E- 1.45E- > 1.00E- 25 7 04 04 06 06 05 04 U ACC- 8.73 E- > 1. 00E- 2.52E- 1. 17E- 1 .16E- 3.87E- 62 06 04 06 06 05 05 Ovarian Cancer IGRO VI 3.83E- > 1 .00E- 1 .90E- 2. 1 5E- 1 .39E- 6.26E- 05 04 06 06 05 05 0 VC AR 6.31E- > 1 · 00E- 2.93E- 2.21E- 1. .41E- 6.99E- -3 05 04 06 06 05 05 0 VC AR > 1. 00E- > 1 .00E- 3. 1 4E- 1. 5 7E- 1. 5 0E- > 1 .00E- -4 04 04 06 06 05 04 0 VC AR > 1 .00E- 5.51E- 2.42E- 1. 42E- 1 .67E- 5. 1 4E- -5 04 05 06 06 05 0 5 0 VC AR 9.8 8E- 4.29E- 1 .49E- 5 .29E- 5. 84E- 3 .39E- -8 06 06 06 07 06 05 SK-0V- 2.11E- 2.89E- 3.51E- 1 .92E- 1 .97E * 0 > 1 .00E- 3 05 05 03 0 6 5 04 Renal Cancer 7 8 6 -0 > 1.00E- 6.92E- 1 .63E- 3 .76E- 1 .48E- 2. 1 9E- 04 06 05 07 0 5 07 A498〉 1. 00E- 4.65E- 4.62E- 1 .72E---04 05 06 06 ACHN > 1.00E- 2.89E- 3.5 5 E- 3 .86E- 1 .54E- 5 .3 8E- 04 05 06 07 05 05 C AKI- 1 > 1 .00E- > 1 .00E- 6.31E- 8.21E- 1. 84E- > 1 .00E- 04 04 06 07 05 04 RXF 2.57E- 9.85E- 1 .63E- 1 .92E----393 05 06 05 06 SN 1 2C > 1 .OOE- 3. 5 6E- 3 .74E- 2.72E--4.60E- 04 06 06 07 05 -------- Order --------- (Please read the note on the back first Please fill in this page for more details) This paper size applies to China National Standard (CNS) A4 (210 X 297 29%) 591006

發明說明（2? 五經濟部智慧財產局員工消費合作社印製 TK- 1 0 > 1 . 〇WT 04 > 1 .00E-04 2.95E- 06 2.22E- 06 1.91E-05 > 1 .00E-04 U 0 - 3 1 > 1 . 0 0 E -04 1 .09E- 05 > 1 .00E-04 1 . 14E-06 - 3 . 14E-05 Prostate Ή广 Ο Lancer P C - 3 > 1 .00E. 04 8.81E- 05 2.49E-06 1 .46E-06 1 .1 1E-05 6.79E- 05 D U - 1 4 5 > 1 .00E. 04 > 1 .00E-04 4. 1 0E-06 1 .3 5E-06 - 7.01E-05 Breast C a n c e r M C F 7 4.94E- 06 > 1 .00E-04 2.95E- 06 2.98E- 07 1 .62E-05 3 .08E-05 M C F 7 / A DR-RES 2.45E- 05 2_71E- 05 5.51E-05 2·15 E-06 1 .04E-05 > 1 .00E-04 M D A -MB- 23 1 /AT CC 3 .82E-06 5.64E- 05 1 .88E-06 7.65E- 07 1 · 3 2 E -05 2.36E- 05 H S 5 7 8 T 3 . 8 4 E -06 3 · 8 8 E -06 1 .53E-06 7.54E- 07 1 .87E-05 3.71E-05 M D A -MB-43 5 8.41E-05 > 1 .00E-04 2.90E- 06 1 .96E-06 1 · 4 1 E -05 5.59E-05 M D A - N 2.46E-05 > 1 . 0 0 E -04 1 .96E-06 1 .42E-06 - 4.65E- 05 BT-5 49 5.03E- 05 4.53E- 06 1 .68E-06 1 ·54Ε-06 1 .30E-05 2.99E- 05 T-4 7 D 4.32E- 06 > 1 .00E-04 2.09E- 06 2.60E- 06 嫌 3.00E-05 由表一中可知對於多種人類癌細胞之細胞株C e 11 line，本發明之式（i )化合物於濃度時，具有有意義之細胞毒殺活性（cytotoxic activity)，而具N- 本紙張尺度卿令國國家標準（CNS)A4規格⑵。X视#餐） ^^衣--------1T--------->^· (請先閱讀背面之注意事項再填寫本頁) 591006Description of the invention (2? Printed by TK- 1 0 > 1. 1.0WT 04 > 1.00E-04 2.95E- 06 2.22E- 06 1.91E-05 > 1. 00E-04 U 0-3 1 > 1. 0 0 E -04 1 .09E- 05 > 1 .00E-04 1. 14E-06-3. 14E-05 Prostate Ή 广〇 Lancer PC-3 > 1 .00E. 04 8.81E- 05 2.49E-06 1 .46E-06 1 .1 1E-05 6.79E- 05 DU-1 4 5 > 1 .00E. 04 > 1 .00E-04 4.1 0E-06 1 .3 5E-06-7.01E-05 Breast C ancer MCF 7 4.94E- 06 > 1 .00E-04 2.95E- 06 2.98E- 07 1 .62E-05 3 .08E-05 MCF 7 / A DR-RES 2.45E- 05 2_71E- 05 5.51E-05 2.15 E-06 1. .04E-05 > 1. .00E-04 MDA -MB- 23 1 / AT CC 3 .82E-06 5.64E -05 1 .88E-06 7.65E- 07 1 · 3 2 E -05 2.36E- 05 HS 5 7 8 T 3. 8 4 E -06 3 · 8 8 E -06 1 .53E-06 7.54E- 07 1 .87E-05 3.71E-05 MDA -MB-43 5 8.41E-05 > 1 .00E-04 2.90E- 06 1 .96E-06 1 · 4 1 E -05 5.59E-05 MDA-N 2.46 E-05 > 1. 0 0 E -04 1 .96E-06 1 .42E-06-4.65E- 05 BT-5 49 5.03E- 05 4.53E- 06 1 .68E-06 1 · 54E-06 1 .30E-05 2.99E- 05 T-4 7 D 4.32E- 06 > 1. 00E-04 2.09E- 06 2.60E- 06 susceptible 3.00E-05 As shown in Table 1, for the cell line C e 11 line of various human cancer cells, The compound of formula (i) has a significant cytotoxic activity at the concentration, and has the N-paper standard (CNS) A4 specification). X 视 # 餐） ^^ 衣 -------- 1T --------- &^; (Please read the precautions on the back before filling this page) 591006

補充丨五、發明說明（2沒）弟二丁氧缓-普林（N-Boc-pr 『基之-式（I )化合物更在nM級濃度更對κ_652 ’ RPMI-8226及SNB-19等細胞株c e 11 1 i n e具有生長抑制活性。故由上可知本案式 (I)化合物確實對人類癌細胞之cell line具有細胞毒殺活性（cytotoxic activity)。惟應注意的是，上述諸多實施例僅係為了便於説明而舉例而已，本發明所主張之權利範圍自應以申請專利範圍所述為準’而非僅限於上述實施例。 (請先閱讀背面之注意事項再填寫本頁) 參衣訂---------線一經濟部智慧財產局員工消費合作社印製本紙張尺度適用中國國家標準（CNS)A4規格（210 X 297公1爱）Complement 丨 Fifth, the description of the invention (2) Di-dioxybutyrin-Prin (N-Boc-pr "based-formula (I) compounds are more compatible with κ_652 'RPMI-8226 and SNB-19, etc. The cell line ce 11 1 ine has growth inhibitory activity. Therefore, it can be seen from the above that the compound of formula (I) in this case does have cytotoxic activity on the cell line of human cancer cells. However, it should be noted that many of the above examples are only For the convenience of explanation, the scope of the rights claimed in the present invention shall be based on the scope of the patent application, and not limited to the above embodiments. (Please read the notes on the back before filling this page) -------- Line 1 Printed by the Consumers' Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs This paper is printed in accordance with China National Standard (CNS) A4 (210 X 297 male 1 love)

Claims

591006 No. 88119382, revised in December 1992 Page A8S8D8 Ben ti # 倐

Benefit range ι · A compound such as formula (i ’) Η

Where η is any integer from 1 to 6; wherein R8 is glycineyl, alaninyl, valinyl, leucinyl, isoleucinyl , Prolinyl, phenylalanyl, methionyl, tryptophyl, serinyl, threoninyl, cysteine Cysteinyl, glutaminyl, a-glutamyl, γ-glutamyl, tyrosinyl, aspartamino asparaginyl), ex-aspartyl (α-aspartyl), β-aspartyl (β_aspartyl), lysinyl, protein amino (argininyl), tissue amino (histidinyl), third N-Boc-glycinyl, N-Boc-alaninyl, N-Boc-valinyl, N-third butoxycarbonyl white amino acid group (N_B〇c-leucin yl), N_ tertiary butoxycarbonyl iso white amino acid group (n_b〇c_ This paper is a standard 1 $ using 7 national standards (CNS) A4 regulations (210 X 297 issued) -------- ----- Scorpion (Please read the precautions on the back before filling this page) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs ^ I «ΙΙΙΙ1Ι1— I Αν— II1IIIIIIIII --- I ------ 591006 Ministry of Economic Affairs Printed by A8, B8, C8, and D8 of the Intellectual Property Bureau's Consumer Cooperative Co., Ltd. (Applicable patent scope of tsoleucinyl), N-Boc-prolinyl, N-Boc-prolinyl amino acid group (NB〇c-phenylalanyl), N-Boc-methionyl, N-Boc-tryptophyl, N · Third-butyl N-Boc-serinyl, N-Boc-threoninyl, N-Boc-cysteinyl , N-Boc-glutaminyl, Nα-Boc-glutaminyl (N, Boc-α-glutamyl), Nα_ third-butoxycarbonyl -γ-glycine amino group (Να-Βοο-γ- glutamyl), N-Boc-tyrosinyl, N-Boc-tyrosinyl (N_Boc__ & 3-port & ^ 8 丨 11 丫 1 ), &Gt; ^-Third-butoxycarbonyl-010-aspartic acid group (> ^-Boc-a-aspartyl), Nα_third-butoxycarbonyl-β_aspartic acid group (Nα-Boc- βaspartyl), N-Boc-lysinyl, N-Boc-lysinyl, Na, Nε • Bac-lysinyl, N-Boc-lysinyl, N-Boc Carbonyl protein amino acid group (^ 80〇argininyl), Na, N · group, two third butoxycarbonyl protein amino acid group (Na, Nguanidinyl-diBoc-argininyl), N-third butoxycarbonyl tissue amino acid group (N- Boc- histidinyl), N-benzyloxycarbonyl-glycinyl, N-benzyloxycarbonyl · N-Cbz-alaninyl, N-benzyloxycarbonyl- Amino acid group (N-Οζ-ναΙίηΥΐ), N-benzyloxycarbonyl-white amino acid group (N_Cbz-leucinyl), N-benzyloxycarbonyl · isowhite amino acid group (N_Cbz- This paper is applicable to Chinese national standards (CNS) A4 specifications (210 X 2973 gold cents) (Please read the precautions on the back before filling in this page) -------- Order --------- Line '591006 A8 B8 C8 D8 cloth, I apply for patent scope \ i | S〇leucinyl ), N_benzyloxycarbonyl_Prinky⑺-^^ • prolinyl), N-benzyloxycarbonyl-primary amino acid group (N_Cbz_phenylalanyl), N-benzyloxycarbonyl_methylthioamino group (N_Cbz-methionyl), benzyloxycarbonyl-color amino acid group (N_cbz_tryptophyl), N-benzyloxycarbonyl-serineyl group, N-benzyloxycarbonyl-isylamino group (N_Cbz-threoninyl), N-benzyloxycarbonyl-cysteine amino group (N_Cbz_cysteinyl), N_benzyloxycarbonyl-glyaminoamino group (N_Cbz_glutaminyl), N'benzyloxycarbonyl_α _Glycine amino group (N, α-glutamyl), Να_benzyloxycarbonyl group N'cbz-γ-glutamyl, N-benzyloxycarbonyl-tyrosinyl group (~ 01 ^ -tyrosinyl ), N-benzyloxycarbonyl aspartame (N-Cbz_asparaginyl), Nα-benzyloxycarbonyl_α_asparagine (Nα_Cbz-α-asp arty 1), Να-benzene Methyloxycarbonyl-β_day Amino acid group (Na-Cbz-P-aspartyl), N-benzyloxycarbonyl-soluble amino acid group (Heart Cbz-lysinyl), Nα, Nε-diphenylmethyloxycarbonyl-soluble amino acid group (Να,, _ 心 (^ 2-17811 ^ 1), cardiac benzyloxycarbonyl protein amino acid group (Heart Cbz-argininyl), Na, N guanidino-diphenylmethyloxycarbonyl protein amino acid group (N \ diCbz-argininyl), N-benzyl N-Cbz-histidinyl, N- (9- 芴) methoxy-glycinyl, N- (9-miao) methoxy- N-Fmoc-alaninyl, N- (9-miao) methoxy-aromatic amino group (N-Fmoc-valinyl), N- (9- 芴) methoxy-white amino acid group (N -Fmoc_leucinyl), N- (9- 芴) Methoxy This paper size is applicable to China National Standard (CNS) A4 (210 X 2973 mm) (Please read the precautions on the back before filling this page) ----- ---- Order --------- Line 1 Printed by Employee Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 591006 Printed by A8 B8 C8 D8 of Employee Cooperative Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs N-Fmoc-isoleuc inyl), N- (9-Miao) ¥ oxy-primary oil amino group (N-Fmoc-alaninyl), N- (9-go) methoxy-fragrant amino acid group (N-Fmoc-valinyl), N- (9- 芴) methoxy · white amino acid group (N-Fmoc-leucinyl), N_ (9 · 芴) methoxy-isowhite amino acid group (N-Fmoc-isoleucinyl), N- (9 -9 ) N-Fmoc-prolinyl, N- (9- 芴) methoxy-N-Fmoc-phenylalanyl, N- (9-go) methoxy -N-Fmoc-methionyl, N- (9-Miao) methoxy · color amino group (N-Fmoc-tryptophyl), N- (9- 芴), methyllactyl-silk amino acid group ( N-Fmoc_serinyl), N- (9- 芴) methoxy-isose amino acid group (N-Fmoc-threoninyl), N · (9-miao) methoxy · cysteine amino group (N-Fmoc-cysteinyl) , N- (9-fluorene) methoxy · glycine amino group (N-Fmoc-glutaminyl), Nα- (9-fluorene) methoxy-01-glycine amino group (> ^-? 111〇 ( ： -01 邙 11 ^ & 11 ^ 1), > ^-(9- 勿) methyllactyl-γ-glycine amino group (1 ^-? 111〇 (: _ 7-glutamyl), N- (9- Don't) N-Fmoc-tyrosinyl, N- ( 9- 芴) methoxy-aspartylamino (~ Fmoc-asparaginyl), Να- (9- 芴) methoxy-α-asparaginyl (Na-Fmoc--a-aspartyl), Να -(9- 芴) methoxy_β_aspartic acid group (Na-Fmoc-p-aspartyl), N- (9- 芴) methoxy-soluble amino acid group (> ^ 卩 111〇 (:-1 } ^ 111; ^ 1), 1 ^ '1 ^ -di (9-charged) methoxy-soluble amino acid group (Na, Ns-diFmoc-lysinyl), N- (9- 笱) methyllactyl-protein amino acid (N-Fmoc-argininyl), Nα, N guanidino_ di (9- 芴) methoxy-protein amino acid group (Nα, Nguanidinyl- This paper size applies to China National Standard (CNS) A4 specifications (210 X 2973 points Li) (Please read the notes on the back before filling this page) Order ----- Line · 591006 A8 B8 C8 D8 —-Six-k Application for Patent Range IdiFmoc-argininyl), N_ (9- 芴) methoxy- Tissue amino acid group: 0 邛 111〇 (:-1 ^ "(1 丨 1 ^ 1), > ^ _ thirdbutoxycarbonyl _"-benzyloxyl (Please read the precautions on the back before filling this page ) N-Boc-Nε-Cbz-lysinyl, Nε-Third-butoxy-Nα-benzyloxy -Soluble amino acid groups (Cbz-lysinyl), Na-Third-butoxycarbonyl-Nε- (9- 芴) methoxy-amino acid-soluble groups (Na-Boc-N, Fmoc-lysinyl), Νε -Third-butoxy-Nα- (9 · 芴) methoxy · soluble amino acid group (Ne_B〇c_ Ν (χ_ Fmoc · lysinyl), Na -benzyloxycarbonyl group Ν, (9_ 芴) methoxy N-Cbz-Ns-Fmoc-lysinyl, -Third-butoxycarbonyl-Nα- (9-fluorenyl) methoxy-ammonium lysine (1110-1) (1 ^ 1) ^ -Third-butoxycarbonyl-] ^ guanidyl_benzyloxycarbonyl_ protein amino acid group (Na-Boc- Nguanidinyl_ cbz & ^ 11 ^ 1 ^ 1), ^^-thirdbutoxycarbonyl- 1 ^ -benzyloxycarbonyl_protein amino acid group (Nguanidinyi_BOC- Να_ Cbz- arginin ^), Να_third butoxycarbonyl_ N pulse group_ (9-芴) methoxy_protein amino acid group Ministry of Economy Printed by the Intellectual Property Bureau's Consumer Cooperative (Na-Boc_ Nguanidinyl- Fmoc- argininyl), N guanidino. The third butoxyl-Nα- (9- 芴) methoxy-protein amino acid group (Nguanidinyl Boc- Na-Fmoc -argininyl), Na-benzyloxycarbonyl_ N guanidino_ (9-¾) methoxy-protein amino acid group (Nα- Fmoc- argi ninyl), N, benzyloxycarbonyl-nguanyl- (9-lean) methoxy-protein amino acid group (Nε-Cbz-Nguanidinyi-Fmoe argininyl), Na-third butoxycarbonyl-nitro-protein Amino acid group (Na- Boc -NguanWW-nitro- argininyl), benzyl & Tibetan group · N, nitro-protein amino acid group (Nα · Cbz _Nguanidinyi) This paper standard applies to China National Standard (CNS) A4 specification (210 X 2973 ^ cent) 591006 A8 B8 C8 D8 No. 88119382, revised in December 1992 Page 6. Application scope of patents nitro-argininyl) or Nα_ (9- 芴) methoxy-Nguanidyl-nitro-protein amino acid group ( Na-Fmoc_Nguanidinyl-nitr.argininyl); and pharmaceutically acceptable salts thereof. 2. The compound as described in item 丨 of the scope of patent application, wherein ^ is 2 or 3. 3. The compound described in item 1 of the scope of patent application, wherein the compound of formula (j,) is a compound represented by formula (Π,): Η 〇 ΗΝ, \ r8

II Formula (II,) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs ^ where R8 is glycinyl, alaninyl, valinyl, leucinyl, isowhite Isol eucinyl, prolinyl, phenylalanyl, methionyl, tryptophyl, silk amino (861: 丨 11; / 1) Isomer amino acid group (111 ^ 011 丨 11 1), cysteinyl amino group, glutaminyl group, a-glutamyl group, γ-gluin amino acid group (Γ-glutamyl), amino acid group (tyrosinyl), asparaginyl amino group (asparaginyl), α-aspartyl amino group (α-aspartyl), β-aspartyl amino group (β-aspartyl), soluble amino acid Base (lysinyl), protein amino acid base (argininyl), tissue amino acid This paper size applies the Chinese National Standard (CNS) A4 specification (210 X $ 今 7 公发) 591006 Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs Consumer Cooperatives A8 B8 C8 D8 Application for Patent Histidyl, N-Bocc glycinyl, N-Bocclaninyl, N-Bocclaninyl, N-Bocc (N-Boc-valinyl), N-Boc-leucinyl, N-Boc-leucinyl, N-Boc-leucinyl, N-Boc N-Boc-prolinyl, N-Boc-phenylalanyl, N-Boc-phenylalanyl, N-βοο-methionyl, N-third butoxycarbonyl amino acid group (~ Boc-tryptophyl), N-third butoxycarbonyl silk amino acid group (~ Boc-serinyl), N-third butoxycarbonyl isose amino acid group (N_B〇c_threoninyl ), N-third butoxycarbonyl cysteine amino group (n_b〇c_cysteinyl), N-third butoxycarbonyl glutamyl amino group (n_b〇c_glutaminyl), Nα-third butoxycarbonyl-α-gel Amino acid group (Να-βο c-α-glut amyl), Να · third butoxycarbonyl_γ_ gum amino group (Na-Boc_Y-glutamyl), N · third butoxycarbonyl amino acid group (N-Boc-tyrosinyl ), N-third Ding N-Boc-asparaginyl, Nα_third butoxycarbonyl-aspartate amino acid (Na-Boc-a-aspartyl), Nα-third butoxycarboxyl_β aspart Amino acid group (Na-Boc-P-aspartyl), N-Boc-lysinyl amino acid group (N-Boc-lysinyl), Nα, Nε-two third butoxycarbonyl-soluble amino acid group (Na, Ne-diBoc- lysinyl), N-N-Boc-argininyl, Nα, N-Cycloyl-II: r, N-Boc-argininyl (Na, NguanidinyLHiT ^) This paper size applies Chinese national standards (CNS) A4 specification (210 X 2973 mm) -------------------- Order --------- (Please read the precautions on the back first Refill this page) Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs 591006 C8 --- ~ -__ _ Scoop, patent application scope argininyi), N-third butoxycarbonyl amino acid group (n_b〇c_ histidinyl), N -Benzyloxycarbonyl_glycinyl (N_cbz — glycinyl), N-benzyloxycarbonyl_primer amino acid (N_cbz_alaninyl), N-benzyloxycarbonyl-aromatic amino group (Ncbz_valinyl), N -Benzyloxycarbonyl -White amino acid group (N_cbz_ leucinyl), N-benzyloxycarbonyl group_iso-white amino acid group (N_cbz_ isoleucylyl), N-benzyloxycarbonyl group_N-Clinyl, N-Cbz-prolinyl, N-benzene N-cbz-phenylalanyl, N-benzyloxycarbonyl_N-Cbz-methionyl, N-benzyloxycarbonyl-color amino acid (N_ Cbz-tryptophyl), N-benzyloxycarbonyl_silinyl group (N_Cbz-serinyl), N-benzyloxycarbonyl · isose amino acid group (N_Cbz-threoninyl), N-benzyloxycarbonyl half Cys amino acid group (N-Cbz_cySteinyl), N-benzyloxycarbonyl group_glycinamino group (N-Cbz-gUtaminyl), Nα-benzyloxycarbonyl group_α-gluin amino group (Na-a-glutamyl) , Nα_benzyloxycarbonyl_γ · glycine amino group (1 ^-(^ 2 ^ 1111 & 1 ^ 1), 1 ^ -benzyloxycarbonyl-casein amino acid group (^ 0 ^ 2-1 乂 1 '〇3 丨 1 ^ 1), > ^ benzyloxycarbonyl-aspartylamino (N-Cbz-asparaginyl), Nα-benzyloxycarbonyl-α-asparaginyl (1 ^- (^ 2-0143? 31 ^ 1), 1 ^ -benzyloxycarbonyl-β-aspartate (Na-Cbz-p-aspartyl), N -N-Cbz-lysinyl, Nα, Nε-Diphenylmethyloxoyl-amino acid group (Nα, N, diCbz-lysinyl), N-Benzyloxy Carbonyl protein amino acid group (N-Cbz -argininy 1), Να, this paper size is applicable to China National Standard (CNS) A4 specification (210 X 2973 centimeters) ----------- installation ---- ---- Order --------- line (please read the precautions on the back before filling this page) 591006 Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs A8 B8 C8 D8 VI. Application scope of patents N Guanidine-diphenylmethyloxycarbonyl protein amino acid group (Nα, Nguanidiny 丨 -diCbz-argininyl), N-benzyloxyl-tissue amino acid group (N-Cbz-histidinyl), N- (9- 芴) N-Fmoc-glycinyl (N-Fmoc-glycinyl), N- (9-Go) methoxy priming amino acid (N-Fmoc-alaninyl), N_ (9- 芴) methoxy-aromatic amino group (N-Fmoc-valinyl), N- (9- 芴) methoxy-white amino acid group (N_Fmoc-leucinyl), N- (9- 芴) methoxy-isowhite amino acid group (N-Fmoc_isoleucinyl), N -(9-Go) methoxy-virgin oil amino acid group (N-Fmoc-ala ninyl), N- (9-Dutch) methoxy-aromatic amino group (N-Fmoc-valinyl), N- (9 · Miao) methoxy-white amino acid group (N-Fmoc-leucinyl), N- ( 9-Gol) methoxy-iso-white amino acid group (N-Fmoc-isol euciny 1), N- (9-fluorene) methoxy-plinyl (N-Fmoc-prolinyl), N- (9-Gol ) N-Fmoc-phenylalanyl (N-Fmoc-phenylalanyl), N- (9- 芴) methoxy-methylthioamino (N-Pιηοο-η ^ ΐΜοηγίρΝ- (9- 芴) methoxy- Chromoamino group (] ^ _ Fmoc-Uyptophyl), N- (9-Go) methoxy-serinyl group (N-Fmoc-serinyl), N- (9-fluorene) methoxy-isose amino acid group ( N-Fmoc-threoninyl), N- (9-fluorene) methoxy-cysteine amino group (N-Fmoc-cysteinyl), N- (9-fluorene) methoxy_ gum amino acid amino group (N-Fmoc- glutaminyl), Να- (9- 苟) methoxy-α-glycine amino group (Na-Fmoc-a-glutamyl), Να- (9- 芴) methoxy-γ-glycine amino group (Na-Fmoci- glutamyl), Ν- (9- 芴) methoxy-casein amino acid basic paper size applicable to China National Standard (CNS) A4 specification (210 X 2974 baths) --------------- ---- I- ------ (Please read the precautions on the back before filling this page) 591006 A8 B8 C8 D8 will invite the scope of patents (please read the precautions on the back before filling this page) Fmoc-tyrosinyl), N- (9-fluorenyl) methoxy-asparaginylamino (N-Fmoc-asparaginyl), Nα_ (9_fluorenyl) methoxy-cx-asparagine amino acid (Na-Fmoc- -a-aspartyl), Να- (9-芴) methoxy-β-aspartic acid group (Na-Fmoc_P-aspartyl), N- (9-glycol) methoxy-soluble amino acid group (N-Fmoc- lysinyl), Να, Νε-bis (9- 芴) methoxy-lysine amino group (Nα, N, diFmoc-lysinyl), N- (9-9) methoxy-protein amino acid group (& Fmoc-argininyl ), Na, N glycosyl-di (9- 芴) methoxy protein amino acid group (Na, Nguanidinyl-diFmoc-argininyl), N- (9- 芴) methoxy-tissue amino acid group (N-Fmoc-histidinyl ), Na-third butoxycarbonyl-Nε-benzyloxycarbonyl-soluble amino acid group (Na_Boc- Νε- Cbz- lysinyl), Ns-third butoxycarbonyl-Na-benzyloxycarbonyl-soluble amino acid group (Νε-Βοο- Na-Cbz- lysinyl), Na- Tributoxycarbonyl-Nε- (9- 芴) methoxy-lysinyl group (Na-Boc- Ne-Fmoc-lysinyl), Νε-third butoxycarbonyl-Να- (9 · 芴) methoxy group · NS-Boc-Na-Fmoc-lysinyl, Na-benzyloxyl-Nε- (9- 谈) methoxy-amino acid-soluble (Na-Cbz-Ns-Fmoc-lysinyl), Ns-third butoxycarbonyl-Na- (9-fluorene) methoxy-soluble amino group (Ne-Boc-Na-Fmoc-lysinyl), Na third butoxycarbonyl-N ^ -benzyloxycarbonyl group— Protein amino acid group (Na-B0C-inyl- Cbz_ argininyl), N * group-third butoxy group_ Nα-benzyloxycarbonyl-protein amino acid group (Nguanidinyl-B0C-Nα- Cbz- argininyi), Να- 第Tributoxycarbonyl-N-Morphyl- (9- This paper size is applicable to Chinese National Standard (CNS) A4 specification (2 ^ X2416%) 591006 No. 88119382, revised in December 1992. Sixth, the scope of patent application please) Amino acid-protein amino acid group (Na_B〇c_ Nguanidiny1 · * Fm〇C-argininyl), third butoxycarbonyl_ Να㈣ (9㈣芴) methoxy-protein amino acid group (NgUanid-LB () (^ Na_FmQC_ argininyl), N, phenyl fluorenyloxycarbonyl _ N__ (bu 芴) fluorenyl-egg Na-Cbz-Nguanidinyl-Fmoc-argininyl, Ne-phenylfluorenyloxyquinyl-n-oxyl_ (9-fluorenyl) oxy-protein amino acid group (Nε-Cbz-Nguanidinyi_Fmoc- argininyl), N, tertiary butoxycarbonyl ·, nitro-protein amino acid group (NL Boc ⑷ "Lnitr0-argininyl), Na · phenylfluorenyloxycarbonyl group-N vein group-nitro-protein amino acid group (N, cbz _ anidlnyl-nitro_ argininyl) or Να- (9_ 芴) methoxy_ Ν-shishokyl-protein Dunyl acid (Na-Fmoc- Nguanidinyl-nitro-argininyl); and pharmaceutically acceptable salts thereof. 4 · The compound as described in item i of the Shenyan patent scope, wherein the compound of formula (i,) is 1,4-bis {{2-[(Να- 三 Butoxycarbonyl-Nε-phenylfluorenyloxy- Soluble amino acid group) amino group] ethyl} amino group 9,1 0 -anthracene; (l, 4-bis {{2- [(Na- Boc- Νε- Cbz- lysinyl) ami η ο] e thy 1} ami η ο}-9,1 0- anthracenedione) ο 5 · The compound described in item i of the scope of patent application, wherein the compound of formula (〗,) is 1,4-di {{2-[(soluble amino acid group) Amine] ethyl} amino} -9,10-anthracene; (i, 4-bis {{2_ [(lysinyl) amino) ethyl} amino} -9,10-anthracenedione) and pharmaceutically acceptable Accepted salts. This paper size applies to the 0 National Standard (CNS) A4 specification (will be issued in 210 X 297) ------------ 丨螓 (please read the precautions on the back before filling this page) Ministry of Economic Affairs Printed by the Intellectual Property Bureau Staff Consumer Cooperative ^ ^ ----- 1 --- ^ 1® .----------------------- 591006 ABCD Γ, Application Scope of patent 6 · The compound as described in item 1 of the scope of patent application, wherein the compound of formula (ι,) is 1,4-bis {{2-[(N-didioxo-methylthioamino) amino ] Ethyl} amino} -9,10-anthraquinone; (1,4 讣 4 {{2- [(N-B oc-methioniny 1) amino] ethyl} amino} -9,1〇-anthracenedione) 〇 7. The compound as described in item i of the scope of patent application, wherein the compound of formula (j) is 1,4-bis {{2-[(methylthioamino) amino] ethyl} amino} -9,10 -Anthraquinone; (l, 4_bis {{2- [(methioninyl) amino] ethyl} amino} _9, l0_ anthracenedione) and pharmaceutically acceptable salts thereof. 8 · The compound as described in item 1 of the scope of patent application, wherein the compound of formula (), is I, 4-di {{2-[(N-third butoxycarbonyl-prinyl) amino] ethyl } Amine} -9,10-anthraquinone; (1,4_bis {{2- [(N_ B〇C-pr〇liny " amin〇] ethyl} amin〇} _ 9? 1O-anthracenedione) ° 9 · 如The compound described in item 1 of the scope of the patent application, wherein the compound of formula (I,) is 1,4-bis {{2-[(prinyl) amino] ethyl} amino} -9,10-anthracene ; (1,4 ~ bis ({2-[(prolinyl) amino] ethyl} amino} -9 1 〇anA ”·,; 5lu-anthracenedione) and pharmaceutically acceptable salts thereof. Ι〇 · A kind of inhibiting cancer Cell-active medicinal composition, which includes a medically effective dose of a chemical character as described in item 1 of the scope of patent application, and a pharmaceutically acceptable carrier. The i-scale of this paper applies the Chinese National Standard (CNS) A4 specification ( 21〇 ^^) (Please read the precautions before filling out this page), 11 Printed by the Ministry of Economic Affairs 4 ^ M Industrial Consumer Cooperative Cooperative Printed by the Ministry of Economic Affairs Intellectual Property Bureau Employee Cooperative Cooperative Printed 591006 A8 No. 88119382, Rev. I, February 1992 Page D6 6. Patent application scope 1 1 · The pharmaceutical composition as described in the patent application scope No.! 0, which is used to treat lung cancer, blood cancer or brain cancer. 12 · —A method for producing a compound such as formula (II,), Η Ο Η〆R8

R8 is glycinyl, alaninyl, valinyl, leucinyl, isoleucinyl, prolinyl, benzene naphtha Amino acid (phenylalany 1), methionyl, tryptophyl, serinyl, threoninyl, cysteinyl, amidoamine Glutaminyl, α-glutamyl, γ-glutamyl, tyrosinyl, asparaginyl, α-asparaginyl (A_aspartyl), β-aspartyl, β-aspartyl, lysinyl, protein amino (argininyl), histone amino (histidinyl), 1 ^ [-third butoxycarbonyl glycan amino group (&Gt; ^-6〇〇117 (^ 1 ^ 1), > 1-N-Boc-alaninyl), N-Teroxy "China National Standard (CNS) A4 Specification (210 X 2974%) -------- ^ --------- (Please Note on the back of I53ti, please fill out this page again} 591006 Λ8 B8 C8 D8----------- '— -----------—__ 6. Scope of patent application (please read first (Notes on the back, please fill in this page again.) Ministry of Economic Affairs, Smart Assets. 4.P " / Printed by Cooperative Consumer Cooperative, N-Boc-valinyl, Tertiary Butoxy Chiral Acid (N- Boc-leucinyl), N-Boc-isoUncinyl, N-Boc-prolinyl, N-Boc Oil amino group (n_b〇c_phenylalanyl), N_third butoxycarbonyl methionyl amino group (n_b〇c_methionyl), N-third butoxycarbonyl amino acid group (nboc-tryptophyl), N-third N_bOc_serinyl, N-th_boc_threoninyl, N-th_3butoxycarbonylcysteine amino group (^^^ cysteinyl), N -Third-butoxycarbonylaminoamino group (NBOc_gUtaminyl), Nα-Third-butoxycarbonyl-α_glycine amino group (Nα_Boc-oc-gUtamyl), Nα_thirdbutoxycarbonyl_γ- Glycine amino group (Na-Boc-Y_glutamyl), N-third butoxycarbonyl Amino acid group (N_Boc-tyrosinyl), N-third butoxycarbonyl aspartamido amino group (~ Boc-asparaginyl), Na_third butoxycarbonyl-a_aspartic acid amino group (Na-Boc-a- aspartyl), Na-third butoxycarbonyl_β-aspartic acid amino group (^ -60000 ~ 13 口 31 ^ 1), ^ third butoxycarbonyl-soluble amino acid group (N-Boc-lysinyl), Nα, Νε-Second-butoxycarbonyl-soluble amino acid group (Na, Ne_diBoc-lysinyl), N-Third-butoxycarbonyl protein amino acid group (N-Boc-argininyl), Na, N pulse group-Second-three-butoxycarbonyl protein Amino acid group (Na, Nguanidinyl-diBoc-argininyl), N-Boc-histidinyl amino acid group (N-Cocz-glycinyl) , N-benzyloxy retardation, virgin oil amino acid group (N-Cbz-alaninyl), N-benzylamine paper standards applicable to Chinese national standards (CNS > A4 specifications (21〇 > < 2 public (Centi) 591006 A8 B8 C8 D8, 1 — Look at M ................ ~~ ....- '' '_ _ VI 、 Scope of patent application (please read the notes on the back before filling out the tribute) Wisdom of the Ministry of Economic Affairs 4-Industrial Consumer Cooperatives Printed Oxygen N-Cbz-valinyl, n-benzyloxy-N-Cbz-leucinyl, N-Cbz-leuinyl, N-Cbz -isoleucinyl), N-benzyloxy coagulation group-Prinyl (> ^ 211 * 〇1 丨 1 ^ 1), 1 benzyloxycarbonyl group-primary oil amino acid group (N-Cbz-phenylalanyl), N-benzyloxycoagulation group_methylthioamino group (N-Cbz-methionyl), N-benzyloxycoagulation amino acid group (> 1-(^ 24 卩? 1 (^ 1 ^ 1), 1 benzyloxycarbonyl_silinyl amino group (N-Cbz-serinyl), N-benzyloxycarbonyl_isosilyl amino acid group (1 (^ 2411 ^ 011 丨 1 ^ 1) , 1 ^ benzyloxycarbonyl_cysteine amino group (> ^ (^ 2 义乂 316 丨 1 ^ 1), .benzyloxycarbonyl_glycinamino group (N-Cbz-glutaminyl), Nα -Benzyloxycarbonyl_α_glycine amino group (Να_α-glutamyl), Nα_benzyloxycarbonyl gum amino group (Na-Cbz-y-glutamyl), N-benzyloxycarbonyl-tyrosine amino group ( N-Cbz-tyrosinyl), N-benzyloxycarbonyl-asparaginyl (N-Cbz-asparaginyl), Nα · benzyloxyl-α-asparagine (Na-Cbz-a -aspartyl), Nα-benzyloxyl-β-aspartyl amino acid (Na-Cbz-p-aspartyl), N-benzyloxyl amino acid (N-Cbz-lysinyl), Nα, Νε-Diphenylmethyloxycarbonyl amino-soluble group (Nα, Ne-diCbz-lysinyl), N-benzyl lactoyl protein amino group (N-Cbz-argininyl), Na, N diphenylmethyloxyl Amino acid group (^, > ^ 11 & 111 (11 "1-diCbz-argininyl), N-benzyloxycarbonyl_tissue amino acid group (N-Cb z-histidinyl), N- (9- 芴) methoxy-glycininyl group (N-Fmoc-glyCinyl), N- (9_ 芴) methoxy-primary oil amino This paper standard applies to Chinese national standards (CNS) A4 specification (210X2% mm) 591006 A8 B8 C8 D8 VI. A patent scope (please read the precautions on the back before filling this page) Printed by N-Fmbc (N-Fmbc) -alaninyl), N- (9-fluorenyl) methoxy-aromatic amino group (N-Fmoc-valinyl), N- (9-fluorenyl) methoxy-white amino group (N-Fmoc-leucinyl), N- (9- 芴) methoxy-isoleucinyl acid group (N-Fmoc-isoleucinyl), N- (9_ 芴) methoxy-primary oil amino acid group (NF moc-alaninyl), N- (9-- ) N-Fmoc-valinyl, N- (9- 芴) N-Fmoc-leucinyl, N- (9- 芴) methoxy, iso White amino acid group (N-Fmoc-isoleucinyl), N- (9-fluorene) methoxy-prilinyl (N-Fmoc-prolinyl), N- (9-methyl) methoxy-virgin oil amino acid group (NF moc-phenylalany 1), N- (9- 匇) methyllactyl formazan see amino acid group () ^-1 ^ 111〇 (:-methionyl), N- (9- 芴) methoxy-chromoamino group (N-Fmoc-tryptophyl), N- (9- 芴) methoxy-serine amino group (N-Fmoc-serinyl), N_ (9- 芴) methoxy N-Fmoc-threoninyl, N_ (9- 芴) methoxy-cysteine amino group (N-Fmoc-cysteinyl), N- (9- 芴) methoxy-glycolamino group Amino group (N-Fmoc-glutaminyl), Nα- (9-go) methoxy-a-gluamino group (Na-Fmoc-a_glutamyl), Nα- (9- 芴) methoxy-γ-gluamino group (Na-Fmoc-Y-glutamyl), N- (9-¾) methyllactyl-enzyme amino acid group (N-Fmoc-tyros, inyl), N- (9-miao) methoxy- Asparagine amino group (~ Fmoc_asparaginyl), Nα_ (9-fluorene) methoxy_α-aspartic acid amino group (Na-Fmoc--a-aspartyl), Na- (9-fluorene) methoxy-β -Aspartic acid amino group (Na-Fmoc_P-aspartyl), N- (9-gou) This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm)-591006 A BCD application patent scope & group (N-Fmoc-lysinyl), Nα, Νε-: (9-Glu) methoxy-soluble amino acid group (Nα, Ns-diFmoc lysinyl), N- (9- 芴) methoxy_protein amino acid group (N guanidino 9- 芴) methoxy · protein (Please read the notes on the back before filling this page) Fmoc-argininyl), Να, Ν amino acid group (N 'Nguanidi ”i_diFmoc_argininyl), N_ (9- 芴) methoxy-tissue amino group (N_Fmoc_histidinyl), Nα-third butoxycarbonyl-N, benzyloxycarbonyl-soluble amino acid group (Na- Boc- Νε- Cbz- lysinyi), Ne_ tertiary butoxycarbonyl-Na-benzyloxycarbonyl · amino acid-soluble group (n ^ boc-Na-Cbz- lysinyl), Na-tertiary butoxycarbonyl_ ( 9- 芴) methoxy_ Na-Boc- Ne-Fmoc-lysinyl, εε- tertiary butoxycarbonyl_ Να · (9 · 芴) A Na-Fmoc-lysinyl), Na-Fmoc-lysinyl), Nα_benzyloxycarbonyl_Nε_ (9- 芴), methoxy-soluble amino acid (Na-Cbz-NLFm〇 (Mysinyl), Νε-Third-butoxycarbonyl-Na- (9-Go) methoxy-soluble amino acid group (N, Boc-Na-Fmoc-lysinyl), Na-Third-butoxyl-Nguanidyl-benzyl milk Tibetan-protein amino acid group () ^ 01-3〇 (:-1 ^ 11 & 111 (1111 > / 1- Cbz_ argininyl), N-Phenyl-Third-butoxycarbonyl Na_benzyloxycarbonyl-protein amino acid (NgUanidinyl_BQe_ Na_ ebz_ argininyl), Na, Third-butoxycarbonyl_ (9-芴) methoxy_ protein amino acid (Na-Boc- Nguanidinyl_Fmoc_ argininyl), N-guanidyl- third butoxycarbonyl- (9_ 芴) methoxy_ protein amino acid group (Nguanid ~ i_Boc · Na_Fmoc_ argininyl), Na-benzyloxycarbonyl group -芴) Methoxy This paper size is in accordance with Chinese National Standard (CNS) A4 specification (210 X 2 mm) 591006 -1 —---- ------- Ministry of Economic Affairs Smart Money 4, ^ Μ 工Printed by Consumer Cooperatives A 8 B8 C8 D8 Scope of patent application ^ ^ ——- amino-protein amino group (Nα-Cbz-Nguanidinyi X; v-Fmoc-argininyl), Nε_benzyloxycarbonyl group_Nguanidino group ）) Methoxy "gu-protein amino acid group (Nε_CbZ-NL ... F ~ rmoc argininy 1), the second butyl ammonia purple μ guanidino group said a ^ carbon one-carbon-N-nitro-protein amino acid group (Na- Boc _NgUanidinyl_nitr〇_ argininyl), Na_ leather methyloxycarbonyl-Nw_nitro_protein amino acid group (Na_ cbz xjguanidinyl. _Nitro_ argininyl) or (9- 芴) methoxy -__ glycan N-month-nitro-protein amino acid group (Nα-Fmoc_nitro-argininyl); it includes compounds of the following formula (V,)

In the formula (V,), η, R and R are as defined above; a condensation reaction with a coupling agent and an N-protected amino acid is performed. 1 3 · The manufacturing method as described in item 12 of the scope of the patent application, wherein the coupling agent is N, N'-diisopropyl-carbodiimide, N , N'-dicyclohexylcarbodiimide (N, N'-di cyclohexyl carbodiimide), ethyl chloro-formate, carbony diimidazole or ECDI in a solvent. This paper size applies to China National Standard (CNS) A4 specification (210 × 2% "mm) (Please read the precautions on the back before filling this page) 591006 BS CS PB Yixing, patent application scope (Please read the precautions on the back first Refill this page) Printed by the Consumer Cooperatives of the 4th Bureau of Wisdom and Finance of the Ministry of Economic Affairs 4 4. The manufacturing method as described in item 12 of the scope of patent application, wherein the N-protected amino acid is N-third butoxycarbonylpril amino acid ( N-Boc-proline), N-Boc-methione, N-Boc-tryptophan, N-Third Amino acid (N_Boc-serine), N-Boc-threonine, N-Boc-cysteine, N-Toc N-Boc-glutamine, Nα-Na-Boc-glutamic acid, N-Boc-tyrosine, N -N-Boc-asparagine, N-Boc-asparagine, (N-Boc-asparagine), Να, Νε-II-Third-butyl Carbonyl-soluble amino acids (Nα, N, diBoc-lysine), N-Boc-arginine, N-Boc-histidine, N-benzyl N-Cbz-proline, N-Cbz methione, N-Cbz_tryptophan, N- Benzyloxycarbonyl-serine amino acid (N-Cbz-serine), N-benzyloxycarbonyl-isilamino acid (^^ 2_threonine), N-benzyloxycarbonyl-cysteine (N_cbz_cysteine), N-benzyloxycarbonyl-glycolamine (N_cbz_glutamine), Nα · benzyloxycarbonyl-gluin amino acid (N_cbz_glutamic acid), N_benzyloxycarbonyl_tyrosine amino group (N_ Applicable to this paper size) China National Standard (CNS) A4 Specification (210X2?) 591006

Application scope: Cbz-tyrosine), N-benzyloxycarbonyl-asparagine, N-Cbz-aspartic acid, Nα, Nε-benzyloxycarbonyl-lysine (Nα, N, diCbz-lysine), N-benzyloxydynyl-protein amino acid (N-Cbz-arginine), N-benzyloxycarbonyl-tissue amino acid (N-Cbz-histidine), N- (9-fluorene) methoxy-priline amino acid (N-Fmoc-proline), N- (9-fluorene) methoxy-methylthio amino acid (N-Fmoc-methione ), N- (9- 芴) methoxy-color amino acid (N- Fmoc-tryptophan), N- (9_ 芴) methoxy-serine amino acid (N- Fmoc-serine), N- (9-go ) N-Fmoc-threonine, N- (9-Vis) N-Fmoc-cysteine, N- (9-M) methoxy-gum N-F moc-glutamine, Nα- (9-Miao) methoxy · glycine (Na-Fmoc-glutamic acid), N- (9-%) methoxy-cool amino acid group (N -Fmoc-tyrosine), N- (9- 芴) methoxy-aspartylamine (N- Fmoc-asparagine ^ N- (9- 芴) methoxy- Winter amino acid (> ^ Fmoc-aspartic acid), Na, Nε-bis (9, 芴) methoxy-soluble amino acid (Na, Ne_diFmoc-lysine), N- (9- 芴) methoxy-protein amino acid ( N-Fmoc-arginine) or N- (9- 芴) methoxy-tissue amino acid (N-Fmoc-histidine) ◦ This paper size applies to China National Standard (CNS) A4 (210 X 297¾%) ---- ---- Order --------- line (Please read the notes on the back before filling this page) Printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs