TW434225B - N-[3-(acridin-9-yl)amino-5-hydroxymethyl] phenylcarbamate derivatives, processes and intermediates for their preparation and pharmaceutical compositions thereof - Google Patents

Abstract

The invention provides a compound of the following formula: wherein R1 is C1-6 alkyl; or phenyl; R2 is hydrogen; an acyl group of the formula -CORa wherein Ra is C1-6 alkyl or phenyl; or an acetylalkylcarbonyl group of the formula -CO(CH2)nCOCH3 wherein n=1-3; and R3 and R4 are substituents at different position(s) of the acridine ring (i.e. C-1' - C-8'), and R3 and R4 may be the same or different and independently represent: hydrogen; C1-6 alkyl; C1-6 alkyloxy; a nitro group; an amino group of the formula -NRbRc wherein Rb and Rc may be the same or different and independently represent hydrogen or C1-6 alkyl; an aminoalkylamino group of the formula -NH(CH2)nNRdRe wherein Rd and Re may be the same or different and independently represent hydrogen, C1-6 alkyl, a hydroxyalkyl group of the formula -(CH2)nOH wherein n=1-3, or C1-6 haloalkyl; an alkylaminocarbonyl group of the formula -CONHRf wherein Rf is C1-6 alkyl; an alkylaminoalkylaminocarbonyl group of the formula -CONH(CH2)nNRgRh wherein n=1-5, and Rg and Rh may be the same or different and independently represent hydrogen, C1-6 alkyl, or a nitro group; a halogen group; a hydroxyalkyl group of the formula -(CH2)nOH wherein n=1-3; a carbamate group of the formula -CH2CONHRf wherein Rf is as defined above; an alkylcarbonyloxymethyl group of the formula -CH2OCORf wherein Rf is as defined above; an alkyl sulfonate of the formula -SO3Rf wherein Rf is as defined above; and an alkylsulfonyl group of the formula -SO2Rf wherein Rf is as defined above; with the proviso that when R2, R3 and R4 are hydrogen, R1 is not t-butyl; and the pharmaceutically acceptable salts thereof. The present invention also relates to a process for synthesizing the above-identified compound, intermediate compounds produced thereby, and pharmaceutical compositions comprising the above compounds.

Description

434225 A7 B7 V. Description of the invention (1)

I. Exemplary inventions The present invention relates to N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylamine phosphonate derivatives, methods and intermediates for preparing them, Pharmaceutical composition with the derivative and intermediate. BACKGROUND OF THE INVENTION 9-Anilinoacridine derivatives have undergone intensive research. They are an effective antitumor agent because they can be embedded in double-stranded DNA and are inhibitors of Topo II. A variety of 9-anilinoacridine derivatives and their structure-activity relationships have been reported; refer to, for example, Atwell et al., J. Med. Chem. 1972, 15: 611; Cain et al., J. Med. Chem 1974, 17: 922; Cain et al, J. Med. Chem. 1975, 18: 1110; and Rewcastle et al—, J. Med. Chem—1986, 29: 472 = 4'- (9-acridylamino) methanesulfo-m-methoxyaniline (abbreviated as m-amsacrine or m-AMSA) and its 5-methyl-4-methylcarboxamide derivative (referred to as CI- 921) is the most interesting. Cain et al., Eur. J. Cancer 1974, 10: 539 and Arlin Z., Cancer Treat. Rep-Printed by the Consumers ’Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (please read the precautions on the back before filling this page) 1983 , 967 reports the clinical use of m-AMSA for the treatment of acute leukemia. Baguley et al., Cancer Res. 1984, 44: 3245 and Denny et al., J, Med. Chem. 1987, 30: 658 revealed the second phase of CI-921 in the treatment of leukemia and solid tumors. The antitumor activity of m-AMSA is related to the cleavage of double-stranded DNA by Topo II, which is caused by a common mechanism of DNA-intercalators; see, for example, Nelson et ai., Proc. Natl. Acad · Sci. USA, 1984, 81: 1364 and Pommier et al., Cancer Res. 1985, 41: 3143. Both m-AMSA and CI-921 have methanesulfonium and methoxy functional groups on the Cr and C 彳 positions on the aniline ring, which can be chemically or lysosome reversibly oxidized. Standard (CNS) A4 size (210X297 mm) Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives 434225 at B7 V. Description of the invention (2) The application should be derived from Kundiimine (m-AQDI); see for example Shoemaker et al., Cancer Res. 1984, 44: 1939 and Shoemaker et al., Drug Metab. Dispos. 1982, 10:35. M-AMSA is used to treat mice and rats. The main two metabolites of this preparation are 5'- and -glutathione (GSH) conjugates, without C9-GSH cohabitation; see the previous article. Shoemaker et al., Cancer Res. 1984, 44: 1939; Shoemaker et al., Drug Metab. Dispos. 1982, 10:35; Robertson et al., Drug Metab. Drug Interact. 1988, 6 : 371; and Robertson et al ', Xenobiotica 1992, 22: 657. For CI-921, in addition to the y- and 6'-GSH conjugates, two other metabolites can be measured, namely C9-GSH and the 4-hydroxymethyl derivative of CI-921 (see Robertson et al., Xenobiotica 1992, 22: 657). When the mice were treated with the two agents, more than 50% of the dose was secreted into the glutathione conjugate in bile ° m, and the half-life of AMSA in mouse blood at 37 ° C was about 30 minutes. See, for example, the aforementioned Shoemaker Drug Metab. Dispos. 1982, 10:35 and Robertson et al., Drug Metab ,, Drug Interact. 1988, 6: 371. Recently, Chou et al., Am. Assoc. Cancer Res. 1994, 368 revealed a series of 9-anilino acridine analogs in which the 9-amino group was replaced by a monooxy or sulfur atom, or the compound The para-substituent of the 9-amine functional group of the acridine ring is missing. These novel series of compounds are not oxidized to form diiminoquinone intermediates. Therefore, drugs with higher chemotherapeutic effects are expected to have a longer pot life. Among these compounds, 3- (acridin-9-yl) amino-5-hydroxymethylaniline (AHMA) has significant antitumor activity in vitro and in vivo. The preliminary antitumor activity measured by AHMA and its derivatives shows: 1) AHMA and -5-This paper ruler and applicable Chinese National Standard (CNS) A4 specification (210 X 297 mm) (please read the note f on the back first) (Fill in this page again) ό Binding, / 434225 A7 B7 V. Description of the invention (3) Its derivatives are a group of novel antitumor agents, and its plasma half-life (15 hours) is longer than that of m-AMS A, and 2) AHMA is more effective against murine leukemia and solid tumors (breast adenoma 'B-16 melanoma and Lewy lung cancer) than m_AMSA and VP-16, but less toxic to the host.

Su Gt 3,1 ,, Journal of Medicinal Chemistry 1995 38'17 reveals 1 ^ _ (third butoxyl) -3- (9-acrylamino) and 5_ (hydroxymethyl) aniline for the preparation of N -Methylcarbamic acid intermediate of 3- (9-acridinylamino _) _ 5-aminobenzyl ester. However, the article did not reveal the pharmacological compatibility of the intermediate. We have now unexpectedly found that AHMA's N-co-oxycarbonyl derivatives (ie [3-acridin-9-yl) amino-5 -hydroxy-methyl] phenylcarbamate derivatives) have better in vitro and in vivo properties than their precursor AMHA Internal antitumor efficacy (please refer to Tables 1 and 2 below). SUMMARY OF THE INVENTION Therefore, the present invention provides a compound of formula (Ϊ) (please read the precautions on the back before filling out this page). Cooperatives Indica NHCOOR1

-6-This paper size applies to China National Standard (CNS) A4 (210X 297 mm) 434225 A7 _____B7___ V. Description of the invention (4) where R is Ci-C (5 aryl; or phenyl; R2 is hydrogen ; A fluorenyl group of the formula -CORa, where! ^ Is a Cl_C6 alkyl group or a phenyl group; or an ethanoyl carbonyl group of -CO (CH2) aCOCH3, where n = 1 to 3; and R3 and R4 are on an acridine ring Substituents at different positions (ie OrC-8,), and R3 and R4 may be the same or different, and individually represent: hydrogen; * Ci-Cg alkyl; (^-(: 6alkoxy; nitro: with formula -NRbR ° amine groups, where # and R ° may be the same or different, and each represents hydrogen or Ci-Ce alkyl; an amine alkylamino group of the formula -NH (CH2) nNRdRe, where 1 ^ and Re may be the same or different , Individually represents hydrogen 'CrC6 alkyl group, hydroxyalkyl group with formula (CH2) DOH, where n = 1 to 3, or CKC6i alkyl group; alkylamine carbonyl group with -CONHRf, where: group; Central Bureau of Standards, Ministry of Economic Affairs Printed by the employee's consumer cooperative (please read the precautions on the back before filling out this page) Formula -CONH (CH2) nNRgRh alkylamine alkylamine carbonyl group, where n = 1. .5, and 118 and Rh can be the same or different, individually Represents hydrogen, Cl-C6 tiger Nitro; Halo group: hydroxyalkyl group with formula-(CH2) nOH, where n = l-3; carbamate group with formula -CH2CONHRf, in which the Chinese national standard applies to the paper size as previously defined ( CNS) A4 specification (210X297 mm) 434225 A7 B7 V. Description of the invention (5) · Meaning; Alkylcarbonyloxymethyl group of formula -CH2〇CO〇Rf, where Rf is as defined above; Formula -S〇3Rf The acidic ester group, in which Rf is as previously defined; the alkanesulfonyl group of the formula -S02Rf, in which as defined previously; the prerequisite is that when R2, trans3 and R4 are hydrogen, R1 is not Third butyl; and its pharmaceutically acceptable salt = The present invention also provides a method for preparing a compound of formula (), which comprises: ⑻ condensing a mono-, di- or poly-substituted 9 _ gasified p under appropriate conditions Yakido and 3,5-diaminobenzyl alcohol dihydrogenate form mono-, di-, or poly-substituted 3-(acridin-9-yl) amino-5 -hydroxymethylaniline (please (Please read the notes on the back before filling out this page) Printed by the Central Ministry of Economic Affairs and printed by the Employee Consumer Cooperative

Wherein R3 and R4 are as defined above; (b) a compound of formula (Π) and a haloformate of formula xc00R1 (where X is a halogen, and it is Ci-Ce alkyl or optionally substituted Phenyl) reacts under appropriate conditions to produce compounds of formula (I) where R2 is hydrogen; -8- This paper is sized to the Chinese National Standard (CNS) A4 (210X297 mm)

'-• IT 43 ^ 225 A7 B7 V. Description of the invention (6) (C): ¾ It is necessary to' formate the compound of formula (I) in which R2 is hydrogen under appropriate peaks and generate R2 in which ^ a ' . ', A fluorenyl group of formula -CORa (wherein Ra is (^ (: 6 alkyl) (compound of formula ：: or R2 is of formula-⑶ (CH2) nC0CH3 = ethyl alcohol M group (where n = 1_3) (D) if necessary, suitably _ +, τ, convert the compound of formula (I) into its pharmaceutically acceptable salt. Γττ, + in the middle of formula (11) formed in step (b) Most of the compounds are novel compounds. Therefore, the present invention also follows. Knowing—A new compound of formula (11) (please read the precautions on the back before filling this page)

THjOH -R3

'1T Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs (Π) where R3 and R4 are as defined above; the prerequisite is that at least one of 113 and " is not hydrogen: and its pharmaceutically acceptable salt 3 A pharmaceutical composition is provided, which contains an effective amount of a compound of formula (〗) as an active ingredient. This paper uses Chinese National Standard (CNS) A4 specifications (210 X 297 mm) 4 3 4P? 5 A7 B7 V. Invention Description (7 NHCOOR1

'CI ^ OR ^ R3 (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs / (I) Which is considered to be stilbene-alkyl; or phenyl; R2 is hydrogen; A fluorenyl group of the formula -CORa, where: ^ is Cl-C6 alkyl or phenyl; or an acetanylcarbonyl group with -CO (CH2) aCOCH3, where n = 1 to 3; and R3 and R4 are different positions on the acridine ring Substituents (卽 and R3 and R4 may be the same or different, and individually represent:) 'rat; Ci-G alkyl; CVC6 alkoxy; nitro: amine group of formula -NRbRc, where ^ and Rc may be the same Different J-gases represent nitrogen or pit foundation; each --- I ------- order-J ---- / This paper size applies to China National Standard (CNS M4 specification (210X297 mm) 434225 Economy Printed by the Consumer Standards Cooperative of the Ministry of Standards of the People's Republic of China A7 B7 V. Invention Description (8)

I has an amine alkylamine group of the formula -NH (CH2) nNRdRe, and Re may be the same or different. Individually represents hydrogen, a CVC6 alkyl group, a hydroxyalkyl group of the formula-(CH2) flOH, where n = 1 to 3, Or CrCe haloalkyl; alkylamine carbonyl with -CONHRf, where "is CkQ alkyl; alkylamine alkylcarbonyl with formula -CONH (CH2) nNRgRh, where n« l-5 'and Rs and Rh may be the same or Different, each represents hydrogen, alkyl or nitro; halogen group: a hydroxyalkyl group of the formula-(CH2) nOH, where n = 1 to 3; • a carbamate group of the formula -CH2CONHRf, where R / is as defined above; alkylcarbonyloxymethyl group of formula -CH2OCORf, where Rf is as previously defined; alkyl sulfonate group of formula -S03Rf, where Rf is as previously defined; And its pharmaceutically acceptable salt; and its pharmacologically acceptable carrier. The present invention also provides an active ingredient containing an effective amount of the novel compound of formula (II) as described above and its pharmacologically acceptable Pharmaceutical composition of a carrier. Detailed description of the invention The broadest scope of the present invention is to provide a compound of formula (I) -11-^^ 1 装 ^ ~ 订 J. "线 t # (Please read the back Precautions then fill page) This paper lift scale applies China National Standard (CNS) A4 size (210 > < 297 with well;) 43422 5 A7 B7 five described (9) NHCOOR1 invention

XH ^ OR ^ .R3 (Please read the notes on the back before filling out this page) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs ⑴ where “is Q-C6 alkyl; or phenyl; R2 is hydrogen; CO fluorenyl, where 113 is C ^ -C ^ alkyl or phenyl; or ethanoylcarbonyl with -CO (CH2) nCOCH3, where n = 1 to 3; and R3 and R4 are different on the acridine ring Position of the substituent (ie CrC-8 '), and R3 and R4 may be the same or different, and individually represent: hydrogen; CVC6 alkyl; Ci-C ^^ milk group; nitro: amine group of the formula -NRbRe, where Rb & 1 ^ can be the same or different, and individually represent hydrogen or CrCe alkyl; -12 This paper scale is applicable to China National Standard (CNS) A4 specification (210X297 mm) 434225 Printed by the Central Standards Bureau of the Ministry of Economic Affairs and Consumer Cooperatives Α7 Β7 V. Description of the Invention (ίο)

I has an amine alkylamine group of the formula -NH (CH2) nlNrRdRe, which may be the same or different, and each represents hydrogen 'CrC6 hydrazone, which has the formula-(CHAOH hydroxyalkyl group, where n = 1 to 3, or Haloalkyl; Alkylamine carbonyl with -CONHK /, where 1? / Is (: 1 _ (: 6 alkyl); Alkylamine carbonyl with -CONH (CH2) nNR8Rh, where η = 1. 5 ' And Rh may be the same or different, and individually represent hydrogen, Cl_c6 alkyl or nitro; halogen groups: having a formula-(CH2) n〇Hi via a calcining group, where n = 1-3;-amine methyl having formula -CH2CONHRf Acid ester group, wherein Rf is as previously defined; alkylcarbonyloxymethyl group of formula -CH2OCORf, where Rf is as previously defined; alkyl acid alkyl group of formula -S03Rf, where Rf is as previously defined An alkanesulfonyl group of the formula -S02Rf, as defined previously; the prerequisite is that when R2, "and 4 are hydrogen, ... not a third butyl group; and a pharmaceutically acceptable salt thereof. The term "Q-C6 alkyl" refers to a straight-chain or disproportionated alkyl group containing κ carbon atoms, which includes but is not limited to methyl, ethyl, n-propyl, star-propyl, n-butyl and Tributyl. The term "Cl-C6 fluorenyl" as used herein means 1-6 Originally, straight-chain or branched-chain alkoxy, which includes, but is not limited to, methoxy, ethoxy, propoxy, butoxy, second butoxy, and third butoxy. The word "㈣" or "-1" in the radicals, partly refers to teeth such as m and iodine β. Therefore, the alkyl group may include a fluoroalkyl group and -13.

CNS) A4 Specification (21 OX (Please read the notes on the back before filling in this I). Q- 装 丨 ----— Order-Γί Ϊ -------- --- 434225 Printed by A7 B7, Masonry Consumer Cooperative, Central Bureau of Standards, Ministry of Economic Affairs 5. Description of the invention (") Alkyl groups, such as trifluoromethyl and chloroethyl, etc. For the purpose of illustration, compounds of formula (I) It may be selected from (but not limited to) the following compounds: N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (acridine- 9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; Ν- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isopropyl acetate; Ν- [3- (acridin-9-yl) amino-5-hydroxymethyl N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isobutyl acetate; Nr [3- (acridin-9-yl ) Amino-5-hydroxymethyl] phenylcarbamate benzyl; N- [3- (3-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (3-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (3- ≪ N--9-yl) amino-5-methyl] phenyl n-propylcarbamate; N- [3- (3-methylosis-9-yl) amino-5-5-methyl ] Phenylcarbamate isopropyl ester; N- [3- (3-methyl 11 "Yado-9-yl) amino-5-¾methyl] phenylcarbamate n-butyl ester; N- [3- ( 3-methylacryl-9-yl) amino-5-isomethyl ester via methyl] phenylcarbamate; N- [3- (3-methylacridin-9-yl) amino-5- Isomethyl] phenylcarbamate tertiary butanol; -14- The paper scale is applicable to the Chinese National Standard (CNS) A4 specification (2 丨 〇 X 297 mm) -------- pack -------- Ί Order -Γ ----- ~-(Please read the notes on the back before filling this page} 434225 A7 B7 V. Description of the invention (12) N- [3- (3-methylacridin-9-yl ) Amino-5-hydroxymethyl] phenylcarbamic acid benzene m; N- [3- (4- (Amidinoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid ; N- [3- (4-Amidinoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-methylacridin-9-yl ) N-Amino-5-'hydroxymethyl] phenylcarbamate; N- [3- (4-methylacridin-9-yl) amino-5-hydroxymethyl] phenylamine Isopropyl acid. N- [3- (4- -A Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-butyl; N- [3- (4-methylacridin-9-yl) amino-5-hydroxymethyl] Phenylcarbamic acid isobutyl alcohol; N- [3- (4-methylacridin-9-yl) amino-5-hydroxyfluorenyl] phenylaminocarboxylic acid tert-butyl ester; N- [3- ( 4-Methylacridin-9-yl) amino-5-hydroxyfluorenyl] phenylaminosulfonic acid benzene Printed by the Employees' Cooperatives of the Ministry of Economic Affairs (Please read the precautions on the back before filling out this page ) N-[3- (3-Nitroacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate; N- [3- (3-nitroacridin-9-yl ) Ethyl-5-hydroxymethyl] phenylcarbamate; N- [3- (3-nitroacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate -15- This paper size applies to China National Standard (CNS) A4 (210X297 mm) Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 434225 A7 B7 V. Description of the invention (13) N- [3- (3-nitrate Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate isopropyl; N- [3- (3-nitroacridin-9-yl) amino-5-hydroxymethyl N-butyl phenylcarbamate; N-[3-(3-nitroacridin-9-yl) amino-5 -Isobutyl hydroxymethyl] phenylcarbamate; N- [3- (3-nitroacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid third butyl ester; N- [3- (3-nitroacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid benzene 01-N- [3- (4-nitroacridin-9-yl) amino 5-Hydroxymethyl] phenylaminocarbamate; N- [3- (4, nitroacridin-9-yl) amino-5-hydroxyfluorenyl] phenylaminoacetic acid ethyl ester; N- [3- (4-nitroacridin-9-yl) amino-5-hydroxyfluorenyl] phenylaminoacetic acid n-propyl acetate; N-[3-(4-nitroacridin-9-yl) Amino-5-hydroxymethyl] phenylaminoacetic acid isopropyl acetate; N- [3- (4-nitroacridin-9-yl) amino-5-hydroxymethyl] phenylaminocarboxylic acid n-butyl Vinegar; N- [3- (4-nitroacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isobutyl ester; N-[3-(4-nitroacridin-9 -Base) Amino-5 -Hydroxyfluorenyl] phenylcarbamic acid third butyl ester; '-16-The paper scale is applicable to China's national standard (CNS > A4 specification (2 丨 0X297 mm). Packing ^ ~ Order. ^ _] Line-»(Please read the notes on the back before filling out this page) 434225 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention 14) N- [3- (4-Tyl group 11 "-9-yl) amino-5-phenylmethylphenylphenylcarbamate; N- [3- (3-aminoacridine-9 -Methyl) amino-5-hydroxymethyl] phenylcarbamate; N_ [3- (3-aminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate -[3- (3-Aminoacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacetic acid n-propyl alcohol; N- [3- (3-aminoacridin-9- Isopropyl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (3-aminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate N-butyl ester; N- [3- (3-aminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isobutyl ester; N- [3- (3-aminoamine leaf lake -9-yl) amino-5 -methylbutylphenylcarbamate tert-butyl ester; N- [3- (3-aminoamino-9-yl) amino-5-methyl] phenyl Benzyl carbamate N- [3- (4-Amino-leaf-9-yl) amino-5-methyl-5-methyl] phenylcarbamate; N- [3- (4-Amino-leaf-9 -Amino) amino-5 -Amidino] phenylcarbamate; N- [3- (4-Aminopyridine-9-yl) amino-5 -chimonyl] phenylcarbamate Propyl ester; -17- This paper size is applicable to China National Sample (CNS) A4 ^ (210X297mm) Pack — —Order_ (Read the M items on the back of MUF before filling in this X) 434225 Α7 Β7 Printed by the Consumer Cooperatives of the Central Government Bureau of the Ministry of Economic Affairs V. Description of the invention (15) N- [3- (4-aminoamine leaf lake -9-yl) amino-5-isopropylmethyl via methyl] phenylaminophosphonate; Ν- [3 · (4-amino11-amino-9-yl) amino-5-carboxymethyl] N-butyl phenylaminoacetate; [3- (4-aminoacridin-9-yl) amino-5-hydroxymethyl] phenylaminoformate; N- [3- (4-amine N- [3- (4-Aminoacridine-9-yl) amino-5-5-methyl Phenyl] phenyl carbamate N- [3- (3-methylamino η yam-9-yl) amino-5- via methyl] phenylamine carboxylic acid methyl ester; N_ [3- ( 3-methylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid ethyl ester 1 N- [3- (3-methylaminoacridin-9-yl) amino-5 -N-propyl methylhydroxyphenyl] phenylcarbamate; N- [3- (3.methylamino p amidino-9-yl) amino-5-isopropyl methyl] phenylaminophosphonate; N- [3- (3-methylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-butyl ester; N- [3- (3-methylaminoacridin-9 -Yl) amino-5-hydroxyfluorenyl] Isobutyl aminocarbamate; Ν- [3- (3-methylaminoacridin-9-yl) amino-5, hydroxymethyl] phenylcarbamic acid third butyl ester; -18- Applicable to this paper size China S country (CNS) Α4 specification (210 × 29 · / mm) ~~ ---- -------- installation ----—— order ----, I line (please read first ^ On the back: Please fill in this page for Italian matters) 43422 5 A7 B7 Printed by the Central Government Bureau of the Ministry of Economic Affairs and Consumer Cooperatives V. Description of the invention (16) N- [3- (3-methylaminoacridine-9- Phenyl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-methylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate Purpose; N- [3- (4-methylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacetic acid ethyl ester; N- [3- (4-methylaminoacyl Pyridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-propyl; N- [3- (4-methylaminoacridin-9-yl) amino-5-hydroxymethyl] Isopropyl phenylcarbamate; N- [3- (4- (Amidinoaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- ( 4-Amidinoaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isobutyl ester; N- [3- (4-methylaminoacridin-9-yl) amino- 5-hydroxymethyl ] Phenylcarbamate tert-butyl ester; N- [3- (4-Amidinoaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate phenyl ester; N- [3- ( 3-N, N -dimethylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid methyl ester; N- [3- (3-N, N -dimethylaminoacryl) Pyridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (3-N, N-dimethylaminoacridin-9-yl) amino-5- Hydroxymethyl] n-propyl phenylcarbamate; ^ 19- (Read the M and read the notes on the back before filling this page) ο The paper size of the table is applicable to China National Standard (CNS) A4 specification (2 丨 0X297 mm ) 4 3 4U5 A7 B7 printed by the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs 5. Description of the invention (17) N- [3- (3-N, N-dimethylamine.ylacridin-9-yl) amino group Isopropyl-5-hydroxyamido] phenylaminophosphonate; N- [3- (3-N, N-diamidoaminoacridin-9-yl) amino-5-hydroxymethyl] phenyl N-butyl carbamate; N- [3- (3-N, N-dimethylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate isobutyl ester; N- [3 -(3-N, N-dimethylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid third butyl ester; N- [3- (3-N, N -di Amidoacridine-9- Phenyl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-N, N-dimethylaminoacridin-9-yl) amino-5-hydroxymethyl] Methyl phenylcarbamate; N- [3- (4-N, N-dimethylaminoacridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamate; N- [3 -(4-N, N-dimethylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-propyl ester; N- [3- (4-N, N-difluorene Aminoacridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamate isopropyl; N- [3- (4-N, N-Diamidinoaminoacridin-9-yl) amine N-butyl-5-hydroxymethyl] phenylcarbamate; N- [3- (4-N, N · dimethylaminoacridin-9-yl) amino-5-hydroxymethyl] phenyl Isobutyl carbamate; N- [3- (4-N, N-diamidinoaminoacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacid third butyl ester; -20 -This paper is compliant with China National Standard (CNS) Α4 specification (210 X 297 mm) (Please read the precautions on the back before filling out this page) Binding 434225 Central Consumer Bureau of the Ministry of Economic Affairs, Consumer Consumption Co-operative Print A7 B7 5 Description of the invention (18) N- [3- (4-N, N-dimethylamino 1 * yam-9-yl) amino-5-5-methyl] phenylcarbamic acid benzene ; N- [3- (3-hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacetic acid methyl ester; N- [3- (3-hydroxycarbonylacridine-9- Ethyl) amino-5-hydroxymethyl] phenylaminoacetic acid ethyl ester; N_ [3- (3-hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminocarboxylic acid n-propyl N_ [3- (3-Hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] benzyl carbamic acid isopropyl ester; N- [3- (3-via carbonyl pammazan) 9-yl) amino-5-light methyl]. N-butyl phenylcarbamate; N_ [3- (3- (51-Amino) amidino) amino-5-5-methyl] phenylcarbamate Isobutyl ester; N- [3- (3_Cycloyl 11 amidino-9-yl) amino-5-light methyl] phenylcarbamic acid third butyl ester; N_ [3- (3-hydroxycarbonyl Acridine-9-yl) amino-5-hydroxymethyl] phenylamine phenyl phenyl ester; N- [3- (4- (post-positioned group) "bite-9-yl) amino-5-methyl Methyl] benzylcarbamate; N- [3- (4-hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4- Hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminocarboxylic acid n-propyl I; -21-This paper size applies to China National Standard (CNS) A4 specification (210 × 297 mm) (please first Read back Notes on filling out this page) .ο equipment

, 1T 434226 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (19 N- [3- (4-hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenyl Isopropyl carbamic acid; N- [3- (4-Cycloyl ^^-bita-9-yl) amino-5-c-methyl] phenylcarbamic acid n-butyl ester; N- [3- (4 · Via carbonyl '»Ya-9-yl) amino-5- Via methyl] phenylaminoacetic acid isobutyl ester; Ν-[3- (4 • hydroxycarbonylacridin-9-yl) amino-5 -Hydroxymethyl] phenylcarbamic acid third butyl ester; Ν- [3- (4-hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid phenol; Ν- [3 -(3-Methoxyacridin-9-yl) amino-5-methyl-methyl] phenylcarbamate; N- [3- (3-methoxycarbonylacrid-9-yl) amine N- [3- (fluorenyl) phenylcarbamate; N- [3- (3-methoxypostacryl-9-yl) amino-5-hydroxymethyl] phenylcarbamate ; Ν- [3- (3-methoxymethoxy_yl 1 »yam-9-yl) amino-5-mercapto] phenylcarbamic acid isopropyl ester; Ν- [3- (3- -methoxy Carbonyl acridine-9-yl) amino-5-hydroxymethyl] benzyl carbamic acid Base Isobutyl formate; Ν- [3- (3-methoxymethoxyazine-9-yl) amino-5-¾methyl] phenylcarbamic acid third butyl ester; -22- This paper size applies to China National Standard (CNS) A4 specification (210X297 mm) o- € —— (please read the note on the back ^ before filling this page) Order Γ 434225 A7 B7 Consumer cooperation of the Central Standards Bureau of the Ministry of Economic Affairs 2. Description of the invention (20) N- [3- (3-methoxycarbonylacridin · 9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-methoxy N- (3- (4-methoxycarbonylacridin-9-yl) amino-5-hydroxymethyl] Ethyl phenylaminoacetate; N-[. 3- (4-methoxycarbonylacridin-9-yl) amine plug-5-hydroxymethyl] phenylaminoformate; N- [3- ( 4-Methoxycarbonylacryl-9-yl) amino-5-isomethylpropyl methyl] phenylcarbamate; N- [3- (4-methoxycarbonylacridin-9-yl) amino -5 · hydroxymethyl] phenylcarbamate n-butyl; N, [3- (4-methoxymethoxy P'Γ--9-yl) amino-5-carbamyl] phenylcarbamate iso Butyl ester; Ν- [3- (4-methoxycarbonylacridin-9-yl) amino-5-hydroxymethyl] benzene Tert-butyl amino acid ester; Ν- [3- (4-methoxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid phenyl ester; Ν- [3- (3- Amine-Tanyl-9-yl) amino-5-¾methyl] phenylcarbamate; N- [3- (3-Aminecarboxyl p-Amine-9-yl) amino-5-Zhaomethyl ] Phenylcarbamate; N- [3- (3-aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-propyl acetate; -23- Applicable to this paper size China National Standard (CNS) A4 specification (210 乂 297 mm) nn In in In nn I w {Please read the note on the back before filling in this page) '17 Printed by the Central Standards Bureau of the Ministry of Economic Affairs—Industrial and Consumer Cooperatives 434225 A7 B7 V. Description of the invention (21) N- [3- (3-Aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isopropyl ester; N- [3- ( 3-aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminophosphonium n-butyl ester; N- [3- (3-aminocarbonylacridin-9-yl) amino-5 -Hydroxymethyl] phenylcarbamic acid isobutyl ester; N- [3- (3-aminocarbonylacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamic acid third butyl ester; N- [3- (3-Aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid phenyl ester N- [3- (4-aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-aminocarbonylacridin-9-yl ) Ethyl-5-hydroxyfluorenyl] phenylcarbamate; N- [3- (4-aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate ; N- [3- (4-aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isopropyl ester; N- [3- (4-aminocarbonylacridine-9- N-butylamino) -5-aminomethyl] phenylcarbamate; N- [3- (4-aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacid Isobutyl ester; N- [3- (4-Aminocarbonylacridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamic acid tert-butyl ester; -24- This paper applies Chinese national standards ( CNS) A4 specification (2 丨 0X297mm) (Please read the precautions on the back before filling this page) ΟΎ ^ .----- Ίΐτ-; ----- 〇 Line -------- -434225 Consumption cooperation between employees of the Central Bureau of Standards, Ministry of Economic Affairs, Du printed A7 B7 V. Description of the invention (22) N- [3- (4- (Amine-chitinyl-9-yl) amino-5-methyl) ] Phenylaminophosphonate; N- [3- (3.methylaminezanyl-9-yl) amino-5-kimethyl] phenylcarbamate; N- [3- ( 3-Methylamine, carbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (3-methylaminochidinophyll-9-yl) amino _-5-Ethylmethyl] phenyl n-propyl carboxylate; N- [3- (3- (methylamine-chitino-9-yl) amino-5-phenylmethyl] phenylaminoacetic acid isopropyl Esters; N- [3- (3-methylamine radical-9-fluorene) amino-5-n-methyl] phenylcarbamate n-butyl ester; N- [3- (3-methylamine Yodo-9-yl) amino-5 -methyl] isobutyl isobutyl phenylcarbamate; N- [3- (3- (methylaminezoyl-9-yl) amino-5-methyl) Tert-butyl phenylcarbamate; N- [3- (3-methylaminecarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4 -Amineamine chitosine-9-yl) amino group 5-methyl-5-phenyl] phenylcarbamate; N- [3- (4-methylaminochiridyl-9-yl) amino group -5-Ethylmethyl] phenylcarbamate; N- [3- (4-methylaminesulfonyl-9-yl) amino-5-light methyl] phenylcarbamate;- 25- This paper size is applicable to Chinese National Standard (CNS) 8-4 (2 丨 0X297mm) I (Please read the precautions on the back before filling this page}

43422b DuPont printed A7 B7 produced by the Central Standards Bureau of the Ministry of Economic Affairs V. Explanation of the invention (23), N- [3- (4-methylaminocarbonylacridin-9-yl) amino-5, hydroxymethyl] Isopropyl phenylcarbamate; N- [3- (4-methylaminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4 -Methylaminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminophosphonium isobutyl ester; N- [3- (4-methylaminocarbonylacridin-9-yl) amino- Tert-butyl 5-hydroxymethyl] phenylcarbamate; N- [3- (4-methylaminecarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminophosphonate benzene * ester ; N- [3- (3-N, N-dimethylaminocarbonyl 1 ^ ylam-9-yl) amino-5-methyl-phenyl] carbamate; N- [3- (3- N, N-Dimethylamine-Tanyl-9-yl) amino-5_trimethyl] phenylcarbamate; N- [3- (3-N, N-dimethylaminecarbonylacridine) -9-yl) amino-5-methyl via n-propyl] phenylcarbamate; Ν- [3- (3, N, N · dimethylaminocarbonylacridin-9-yl) amino_5_ Isopropyl] phenylcarbamate; N- [3- (3-N, N-dimethylaminecarbonylacridin-9-yl) aminochimonyl] phenylcarbamate; Ν -[3- (3-Ν, Ν- Sulfonylaminocarbonylacridin-9-yl) amino-5_carboxymethyl] phenylcarbamate isobutyl ester; ） Amine_5_methyl] phenylcarbamate tert-butyl ester: -26- 'The size of the paper method is applicable to Chinese National Standard (CNS) A4 specification (2 丨 0 × 297 mm) —I-(please first Read the notes on the back and fill in this page) Order 434225 Consumption cooperation between employees of the Central Echelon Bureau of the Ministry of Economic Affairs Du printed A7 B7 V. Description of the invention (24) Heart [3- (3-than 1 ^ -dimethylamine carbonyl acryl N- [3- (4-N, N-dimethylaminecarbonylacridin-9-yl) amino group_5_ Methylol] phenylaminophosphonate methyl ester; N- [3- (4-N, N-diamidocarbonylcarbonylacridin-9-yl) amino-5_methyl] phenylaminophosphonate ethyl Ester; 1 ^-[3- (4-ratio: ^ -dimethylaminecarbonylacridine.9-yl) amino-5_methyl] phenyl n-propylammonium acid; N- [3- ( 4-N, N-dimethylaminocarbonylacridin-9-yl) amino-5-methyl via methyl] phenyl, isopropyl carbamate; N- [3- (4-N, N-dimethylamine Carbonylacridin-9-yl) amino-5-5-hydroxymethyl] phenylaminophosphonium n-butyl ester; N- [3- (4-N, N-diamidoaminecarbonyl) Acridine-9-yl) amino-5-5-hydroxymethyl] phenylaminoisobutyrate; N- [3- (4-N, N-dimethylaminocarbonylacridin-9-yl) amino _5 • trimethyl] phenylcarbamate tert-butyl ester; N- [3- (4-N, N-dimethylaminecarbonylacridine · 9-yl) amino group_5_light methyl] phenyl Phenyl amino acid esters; Ν- [3- (3- (methoxy-2-acridin-9-yl) amino-5-hydroxyfluorenyl] phenylaminocarboxylic acid methyl esters; Ν- [3- (3-methyl Oxygen 1: 1 amidin-9-yl) amino-5-¾methyl] phenylamine. Ethyl formate; N- [3- (3-methoxyacridin-9-yl) amino- 5-Hydroxymethyl] phenyl carbamic acid n-propyl vinegar; -27- This paper size is in accordance with China National Standard (CNS) A4 (210X297 mm) (Please read the precautions on the back before filling this page) 0 pack _ 434225 A7 B7 V. Description of the invention (25) N- [3- (3- (Methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isopropyl ester; Ν- [3 -(3-Methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-butyl ester; N- [3- (3-methoxyacridin-9-yl) amine Isobutyl-5-hydroxymethyl] phenylcarbamate; N- [3- (3-methoxyacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate ester N- [3- (3-methoxyacridin-9-yl) amino-5-hydroxymethyl] benzylcarbamic acid phenylhydrazone; N- [3- (4-methoxyacridin-9- Methyl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate Esters; N- [3- (4-methoxyacridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamate n-propyl ester; N- [3- (4-methoxyacridine -9-yl) Amino-5-hydroxyfluorenyl] phenylaminoacetic acid isopropyl ester; Printed by the Consumer Cooperatives of the Standards Bureau of the Ministry of Economic Affairs (Please read the precautions on the back before filling this page) N-[ 3-(4 -Methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-butyl ester; N- [3- (4-methoxyacridin-9-yl) Amino-5 -hydroxymethyl] phenylcarbamic acid isobutyl ester; N- [3- (4- (Hydroxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid third Butyl ester; -28- This paper ruler and the applicable Chinese National Standard (CNS) A4 specification (210X297 mm) 434225 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (26 N- [3- ( 4-Methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylaminophosphonic acid benzene Ester; N- [3- (3-chloroacrid-9-yl) amino-5-acrylic acid methyl ester; N- [3- (3-chloroacid-9-yl) Amino-5-Ethylmethyl] phenylcarbamate ethyl acetate; N-[3- (3-Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-propyl N- [ 3- (3 -Chloroacridine-9-yl) amino-5 -methyl isopropyl carbamic acid isopropyl ester; · N- [3- (3-Ga11 "bit-9-yl) amino -5- ¾methyl] phenylcarbamate n-butyl ester; N- [3- (3 -air lake-9-yl) amino group; 5- ¾methyl] phenylcarbamate isobutyl ester; N- [ 3- (3-Chlorophyll-9-yl) amino-tertiary butyl 5- 5- ¾methyl] phenylcarbamate; N- [3- (3-Apifoliol-9-yl) amino- 5- ¾methyl] phenylcarbamate phenyl vinegar; N- [3- (4-Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate methyl ester; N- [3- (4-Gatriacridin-9-yl) amino-5, hydroxymethyl] phenylcarbamate; N- [3- (4-chloro1 ^ -9-yl) amino-5-¾ Methyl] n-propyl phenylcarbamate; -29- This paper size applies to China's national standard (CNS) A4 size (210 X 297 mm) Packing .. Order ~ • ~ (Please read the precautions on the back before Fill out this page} 434225 Central Ministry of Economy Quasi Bureau employee consumer cooperative print A7 B7 V. Description of the invention (27) n- [3- (4-chloroazine-9-yl) amino-5 · supermethyl] phenylcarbamic acid isopropyl ester: N_ [3- (4-Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-butyl; N- [3- (4-Acridine-9-yl) amino- 5 · Hydroxyfluorenyl] phenylcarbamate isobutyl ester; N- [3- (4-chloroacridin-9-yl) amino-5-5-pentyl] phenylcarbamate tert-butyl ester; n- [3- (4-chloroacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid phenyl ester;-N- [3- (4-Aminocarbonyl-5-methylphylloline-9- Methyl) amino-5-methyl-methyl] phenylaminophosphonate; Ν- [3 · (4-aminocarbonyl-5-methylacridin-9-yl) amino-5-hydroxymethyl] Phenylcarbamate; N- [3- (4-aminocarbonyl-5 -methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3 -(4-aminocarbonyl-5 -methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate isopropyl; Ν- [3- (4-aminocarbonyl-5-methyl Acridine-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamate n-butyl ester; N- [3- (4-aminocarbonyl-5-fluorenylacridin-9-yl) amino-5 -Hydroxyfluorenyl] phenylcarbamate isobutyl ester; Ν- [3 · (4 -Aminocarbonyl-5-fluorenylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid tert-butyl ester; -30- This paper size applies to Chinese National Standards (CNS > Α4 specifications) 210X297 mm) -------- 0 Gangster-Φ I (Please read the precautions on the back before filling this page)

Printed by Du Consumers of Central Bureau of Standards, Ministry of Economic Affairs A7 B7 V. Description of Invention (28)

I N- [3- (4-aminocarbonyl-5-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid phenyl ester; N- [3- (4-methylaminecarbonyl -5-methylacridin-9-yl) amino-5 · hypermethyl] phenylcarbamate; N- [3- (4-methylaminocarbonyl-5 -methylacridin-9-yl ) Amino-5-chimethyl] phenylcarbamate; N- [3- (4-methylaminocarbonyl-5 -methylacridin-9-yl) amino-5 · chimethyl] benzene N-propyl carbamate; N- [3- (4 -fluorenylaminocarbonyl-5 -methylacridin-9 · yl) amino-5-methyl-phenyl] isopropyl carbamate; N- [ 3- (4-Methylaminocarbonyl-5 -methylacridin-9-yl) amino-5-methyl via n-butyl] phenylcarbamate: N- [3_ (4-methylaminecarbonyl-5- Fluorenylacridin-9 · yl) amino-5 + methyl] benzylamine isobutyrate; N- [3- (4-methylaminocarbonyl-5 -methylacridin-9-yl) N- [3- (4-methylaminecarbonyl-5 -fluorenylacridin-9-yl) amino via methyl] phenylaminophosphonic acid benzene Esters; 1 [3- (4-^ > 1-Dimethylaminocarbonyl-5-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid f ester; N- [3 -(4-N, N-dimethylaminocarbonyl-5 -methylacridin-9_yl) amino_5_hydroxymethyl Phenyl] phenylcarbamate N-propyl ester; -31-This paper size applies Chinese National Standard (CNS) A4 size (210 X 297 cm) (Please read the precautions on the back before filling this page) 〇Binding 434225 A7 B7 V. Description of the invention (29) (Please read the notes on the back before filling in this I) N- [3- (4-N, N-dimethylaminocarbonyl-5-methylacridin-9-yl) amino-5— Hydroxymethyl] isopropyl phenylcarbamate; 1 ^-[3- (4- > 1, > ^-dimethylaminecarbonyl-5-methylacridin-9-yl) amino-5- Hydroxymethyl] n-butyl phenylcarbamate; N- [3- (4-N, N-dimethylaminecarbonyl-5-methylacridin-9-yl) amino- 5-hydroxymethyl] benzene Isobutyl carbamic acid; N- [3- (4-N, N-dimethylaminecarbonyl-5-amidinoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid third Butyl ester; N- [3- (4-N, N-dimethylaminocarbonyl-5-methylacridin-9-yl) amino-5-hydroxymethyl · phenyl] phenylcarbamate; N- [3- (4-Aminocarbonyl-5 -methoxyacridin-9-yl) amino-5 -hydroxymethyl] phenylaminophosphonate methyl ester; N- [3- (4-aminocarbonyl -5-methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacetic acid ethyl ester; N- [3- (4-aminocarbonyl-5-methoxyacridin-9) -Yl) amino-5 -hydroxymethyl] phenylpropylammonium n-propyl; N, [3- (4-aminocarbonyl-5-methoxyacridin-9-yl) amino-5 -hydroxy Methyl j isopropyl phenylcarbamate; N- [3- (4- (aminocarbonyl-5-methoxyacridin-9-yl) amino-5-hydroxy) printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs Methyl] n-butyl phenylcarbamate; N- [3- (4-aminocarbonyl-5-methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate isobutyl ; N- [3- (4-Aminocarbonyl-5-methoxyacridin-9-yl) amino-5 -hydroxymethyl] phenylaminotricarboxylic acid tert-butyl ester; -32- Applicable to China National Standard (CNS) A4 specification (210 X 297 mm) Printed by the Consumer Cooperatives of the Central Standardization Bureau of the Ministry of Economic Affairs A7 B7 V. Description of the invention (30) N- [3- (4-aminocarbonyl-5-A Oxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4 · methylaminecarbonyl-5 -methoxyacridin-9-yl) amine Methyl-5 -hydroxymethyl] phenylcarbamate; Ν- [3- (4-methylaminocarbonyl-5-methoxyacridin-9-yl) Methyl-5-hydroxyfluorenyl] phenylcarbamate; N- [3- (4-methylaminocarbonyl-5-methoxyazeto-9-yl) amino-5-hydroxymethyl] phenyl N-propyl carbamate; N- [3- (4-methylaminecarbonyl-5-methoxyacridin-9-yl) amino-5-hydroxymethyl] isopropyl phenylcarbamate; Ν- [ 3- (4-methylaminocarbonyl-5-methoxyacridin-9-yl) amino-5-hydroxyfluorenyl] phenylaminophosphonium n-butyl ester; Ν- [3- (4-fluorenaminecarbonyl · 5-methoxyacridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamic acid isobutyl ester; Ν- [3- (4-methylaminocarbonyl-5-fluorenylacridin- 9-yl) amino-5-hydroxymethyl] phenylcarbamic acid third butyl ester; N- [3- (4-methylaminecarbonyl-5-methoxyacridin-9-yl) amino-5 -Hydroxymethyl] phenylphenyl carbamate; Ν- [3- (4-N, N -dimethylaminocarbonyl-5-methoxyacridin-9-yl) amino-5 -hydroxymethyl] Methyl phenylcarbamate; N- [3- (4-N, N-dimethylaminocarbonyl-5-methoxyacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate Esters; N- [3- (4-N, N-dimethylaminocarbonyl-5-methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; -33 -This paper size applies to Chinese national standard (CNS> M) (210 乂 297mm) (Please read the precautions on the back before filling out this page) ο Install — Q—— 434225 A7 B7 M Printed by the Consumers' Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs V. Invention Description (31 N -[3- (4-N, N -dimethylaminocarbamoyl-5-methoxy-p-bita-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isopropyl ester; & [ 3- (4 ^ 3-Dimethylaminecarbonyl-5-methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid n-butyl ester; · Ν- [3- (4_Ν, Ν-dimethylaminocarbonyl-5-methoxyacridin · 9-yl) amino-5 -hydroxymethyl] phenylcarbamic acid isobutyl ester; ^ [3- (4-: ^, > 1- Dimethylaminocarbonyl-5-methoxyacridine.9_yl) amino-5_hydroxymethyl] benzylcarbamic acid third butyl ester; 1 ^ [3- (4-1 ^, 1 ^ -di Methylaminocarbonyl-5-methoxyacridine. 9-yl) amino-5-5-hydroxymethyl] phenylcarbamic acid phenyl ester; N- [3- (acridin-9-yl) amino-5- Acetyloxymethyl] phenylcarbamate; Ν- [3- (acridin-9-yl) amino-5-hexyloxymethyl] phenylcarbamate; Ν- [3- ( Acryl-9-yl) amino-5-acetamidoxymethyl] phenylcarbamate n-propyl ester;, N- [3- (acridin-9-yl) amino-5 -ethamyloxymethyl ]benzene Iso-urethane iso-ester; N- [3- (acridin-9-yl) amino-5-ethoxymethyl] phenyl-n-butyl carbamate; N- [j- (u 「bit-9- Methyl) amino-5 -ethyl ethyl lactate methyl] phenylcarbamate isobutyl ester; N- [3- (acridin-9-yl) amino-5 -ethylacetoxymethyl] phenylcarbamate Tributyl ester; -34-This paper size is applicable to China National Twin (CNS) A4 specification (210 X 297 mm) I ii " " " 装 τ—Order J (I ~~ (Please read the back of the poem first) Please note this item and fill in this page again} 434225 A7 B7 Printed by the Consumers' Cooperative of the Central Standardization Bureau of the Ministry of Economic Affairs V. Description of the invention (32) N_ [3 _ (acridin-9-yl) amino-5-ethylpyridine Phenyloxymethyl] phenylcarbamate; N- [3- (acridin-9-yl) amino] -5-methylacetoxymethyl] phenylcarbamate; N- [3- (11 Amine-9-yl) amino] -5-ethylacetoxy] benzylaminocarbamate; N- [3- (4- (methylaminojipyl-9-yl) amino-5-ethyl Ethyloxymethyl] phenylcarbamate; N- [3- (4-methylamine tsaminyl-9-yl) amino-5-ethylaminoethyl] phenylaminomethyl ; N- [3- (4-methylaminecarbonyl-5 -methylacridin-9-yl) amino_5_ethoxy Methyl] phenylaminophosphonate; N-[3- (4-methylamine.carbonyl-5-amidoacridin-9-yl) amino-5_ethoxymethyl] phenylcarbamate ethyl Ester; N- [3- (4-methylaminocarbonyl-5 -methoxyacridin-9-yl) amino-5 ethoxymethyl] phenylaminophosphonium ester; Ν- [3 · ( 4-Amidinocarbonyl-5 -methoxymethoxyacridin-9-yl) amino-5 ethyl ethoxymethyl] phenylcarbamate; Ν- [3- (4-amidamine rear 6- Nitro-9-yl) amino-5-methyl-methyl] phenylcarbamate; N- [3- (4-methylaminocarbonyl-6-nitroacridin-9-yl) amino group_ 5-Ethylmethyl] phenylaminoacetic acid ethyl ester; N- [3- (4-methylaminecarbonyl-7-nitroacridin-9-yl) aminomethylethyl] phenylcarbamate; -35- This paper size applies Chinese National Standard (CNS) Α4 size (2! 〇 X 297 mm) H-----1 1 I: ^^^ 1 ^^ 1----- J 1-- ii i-: ~ ^ (please note the back of M1 * before filling out this page) 434225 A7 B7 Consumption cooperation between employees of the Central Bureau of Standards of the Ministry of Economic Affairs 枉 Printing 5. Description of the invention (33 N- [3- (4 -A Aminocarbonyl-7-nitro-p-a-9-yl) amino-5_trimethyl] phenylcarbamate; N- [3- (6-amino-4-methylamine carbon Leaf bite-9-yl) amino-5-methyl.methyl] phenylcarbamate; Ν- [3- (6-amino-4-methylamine-chitinophyll-9-yl) amino _5_Ethylmethyl] phenylcarbamate; Ν- [3- (7-amino-4 -methylaminecarbonylacridin-4-yl) amino_5_Ethylmethyl] phenylcarbamate Methyl esters; Ν- [3- (7-amino-4 -amidocarbonylcarbonylacridin-9-yl) amino-5-pentyl] phenylcarbamate; Ν- [3- (4- Methylaminocarbonyl-6-methylaminoacridin-9 · yl) amino-5 methyl via methyl] phenylcarbamate; Ν ~ [3- (4-methylaminocarbonyl-6-methylaminoacryl) Pyridin-9-yl) amino-5 via methyl] phenylcarbamate; N- [3- (4-methylaminocarbonyl-7-methylaminoacridin-9-yl) amino-5 _Methyl] phenylcarbamate; Ν_ [3- (4.methylaminecarbonyl-7-methylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate ; Ν- [3- (3,6-dinitrodian-9-yl) aminomethyl-methyl] phenylcarbamate; N- [3- (3,6-dinitroacridine-9 -Yl) amino-5-hydroxyfluorenyl] phenylcarbamate; N- [3-(4,5-dinitroacridin-9 -yl) amino-supermethyl] phenylamine Acid esters; -36- This paper size applies to China Jiadong rate (CNS) A4 specification (2I0X297 mm) (Please read the precautions on the back before filling out this page), install ----- ^ — Order J ------ " ° 线 --- -434225 Consumption cooperation between employees of the Central Bureau of Standards, Ministry of Economic Affairs, Du printed A7 B7 V. Description of the invention (34) N- [3- (4,5-dinitroacridine, 9-yl) amino-5-hydroxy Methyl] phenylcarbamate; N- [3- (3,6-diaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3 -(3,6-diaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- {3- [3,6-bis (methylamino) acridine -9-yl] amino-5-hydroxymethyl} phenylcarbamate; N ~ (3- [3,6-bis (methylamino) acridin-9-yl] amino-5-hydroxy Methyl} phenylcarbamate; 1 ^ {3- [4,5-bis (methylamino) acridin-9-yl] amino-5-hydroxymethyl} phenylcarbamate; N_ {3- [4,5-bis (methylamino) acridin-9-yl] amino-5-hydroxymethyl} phenylcarbamate; N_ {3- [3,6 -bis (dimethylformate) Amine) acridin-9-yl] amino-5-hydroxymethyl} phenylcarbamate; N- {3- [3,6-bis (dimethylamino) acridin-9-yl] Amino-5-hydroxymethyl} ethyl urethane; N- {3- [4,5-bis (dimethylamino) acridin-9-yl] amino-5-hydroxymethyl} methyl phenylcarbamate; N_ {3- [4,5-bis (dimethylamino) ) Acridine-9-yl] amino-5-hydroxymethyl} phenylaminoacetic acid ethyl ester; N- {3- [3,6-bis (dimethylaminoethylamino) acridine-9- [Amino] amino-5-hydroxymethyl} phenyl carbamate; -37- This paper size applies to Chinese National Standard (CNS) A4 (2 丨 0X297 mm) ^^^^ 1 n ^ n fn — I— (Please read the note on the back before filling this page) Order 434225 A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (35), N, {3- [3,6- Bis (dimethylaminoethylamino) yodo-9-yl] amino-5-5-methyl} phenylcarbamate; N- {3- [4,5 -bis (dimethylaminoethyl) Amine). Acridine-9-yl] amino-5-methyl} phenylcarbamate; and N- {3- [4,5-bis (dimethylaminoethylamino) acridin-9-yl ] Amine- 5-¾fluorenyl} phenylaminophosphonate ethyl ester 3 Preferred compounds of formula (I) are those in which R2, R3 and R4 are all hydrogen. In a preferred embodiment, R1 is ethyl, and R2, R3, and R4 are hydrogen. A second aspect of the present invention is to provide a method for preparing a compound of formula (I), which covers the board: 适当 Under appropriate conditions, condensing a mono-, di- or poly-substituted 9-gasified acridine with 3,5-diamine Benzyl alcohol dihydrogenate to form mono-, di- or poly-substituted 3-(acridin-9-yl) amino-5 -hydroxymethylaniline with formula (Π)

Where R3 and R4 are as defined above; (b) the compound of formula (11) and the i-formate with the formula XCOOR1 (where X is -38-this paper size uses China National Standard (CNS) A4 specifications ( 210X297 mm) (Please read the notes on the back before filling this page) 434225 A7 B7 V. Description of the invention (36) Halogen, and R1 is CrCe alkyl or optionally substituted phenyl) React under appropriate conditions' Generate a compound of formula (I) where R2 is hydrogen; (C) If necessary, '-halide a compound of formula (J) where R2 is hydrogen under appropriate conditions to generate a fluorenyl group of formula R_Ra (Wherein Ra is a CrC6 gauge group or a phenyl group) a compound of formula (I); or R2 is a compound of formula (I) with an ethyl alcohol group (where n == 1-3) of formula _C0 (CH2) nCOCH3; ⑹ If necessary, the compound of formula (I) is appropriately converted into a pharmaceutically acceptable salt thereof. In the preferred embodiment, the reaction of step ㈤ is in the presence of a test, such as sodium carbonate, potassium carbonate, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, potassium third butoxide, 4, methylmorpholine, Triethylamine, N, N_dimethylaniline,: -diethylbenzylamine, 4- (N, N-diethylamino) pyridine, i 8_diazabicyclo [5.5.0] 11 carbon -7-ene (DBU), 丨, 4_diazabicyclo [2.2.2] octane (TED), 1,5-diazabicyclo [4.3.0] nonyl_5. Male (DBN), In the presence of bases such as 2,6-di-tertiary-butylpyridine, 2,6-tri-tertiary-butylmethyl and other organic bases, it is carried out in a solvent. Ethane, carbon tetrachloride, tetraethylene, or ethers such as diethyl ether, tetrahydrofuran, dioxane, or 2-methoxy ^ I flat L 丞 C), printed by the Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs (Please read the notes on the back before filling this page) Alcohol, such as methanol 'ethanol' propanol, 2-methoxyethanol, or _ a n. 4 ~ 'methylformamide, dimethyl sulfoxide (DMSO) and the like. More preferably, it is based on a mixture of 4 ′ in aerobic imitation and a mixture of methanol and the like, which is contacted for 0.5 hours to two days. The mole ratio of the reactants 9-acridine to 3,5-diaminobenzyl alcohol & and 4-methylmorpholine in step ⑻ can be 1 to 2 to 5, but the ratio is preferably 1 '1 Than 1 Than-39- This paper is from Shicai_Household (CNS) M threats (210X297 public coordinator of the Ministry of Economic Affairs Central Standards Bureau staff consumer cooperation. Printed by the company 434225 Description of the invention (37) f after the response is completed The precipitated products such as ^ (4-methylaminocarbonyl-5_methyl, amidin_9_yl) amino-5_hydroxymethyl can be collected in the air, and the reaction mixture can be concentrated in the air. The residue is diluted with ice-water The precipitated product is then collected by filtration. The product is purified by recrystallization or chromatographic analysis. The treatment in step (b) includes contacting a compound of formula (I) with an alkyl or phenyl formate to form a formula (R2 is hydrogen) (1 ) N-carbamate. In a specific embodiment, the treatment in step (i) includes combining the compound formed in step (ii) with a southern formate having the formula XC00Rl (where X is a halogen such as fluorine, Gas, bromine, iodine, etc., and ^ is Cl_C6 alkyl or optionally substituted phenyl), such as with methyl formate, ethyl chloroformate, n-propyl formate, chloroform Isopropyl ester, tertiary butyl formate, phenyl chloroformate, and the like are contacted to form an alkyl carbamate or phenyl ester of the formula (i) where R2 is hydrogen. In a preferred embodiment with aa, the contact is In the presence of the test, such as sodium carbonate, carbonic acid, sodium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride, emei, 4-methylmorpholine, triethylamine, N, N-dimethylaniline, N , N-diethylaniline, 4- (N, N-diethylamino) pyridine,!, 8-diazabicyclo [5.5 〇] undec-7-ene (DBU), 1,4- Diazabicyclo [2.2.2] octane (TED), 1,5 ^ diazabicyclo [4.3.〇] nonan-5-ene (DBN), 2,6ditributylpyridine, 2, 6-Di-tert-butyl-4-methylpyridine and other organic bases in the presence of bases such as chloroform, digas methane, dichloroethane, carbon tetrachloride, tetramethylene chloride, Or hydrazone, such as diethyl ether, tetrahydrofuran, dioxane or 2-methoxyacetamidine, or dimethylformamide (DMF), dimethylmethane (DMSO), and the like, Under the temperature of _10 to 50. (: 5 minutes to 2 to 40) This paper size is applicable to make the country accurate ( CNS) A4 specification (21 〇X 297 mm) -------- 0- € -----— ΪΤ —---- nv -A (Please read the notes on the back before filling in this Page) Α7 Β7 434225 V. Description of the invention (38) (Please read the notes on the back before filling this page). The solvent is an alcohol, such as methanol, ethanol, propanol or dimethylformamide, two Methylmethylene sulfoxide (DMSO) and the like. Preferably, it is in dimethylformamide (DMF), and is contacted at 0 ° C to room temperature for 15 minutes in the presence of pyridine. In step (b), the molar ratio of the 9-benzylaminoacridine derivative to the alkyl formate or phenyl ester to the base (ie, pyridine) may be 1 to 4 to 6, but preferably 1 to 1. 5 to 2 ° When the reaction in step (b) is completed, the reaction mixture is evaporated to dryness in the air. The product was isolated and purified by recrystallization or chromatography. The treatment in step (c) includes oxidizing a compound of formula (I) in which R2 is hydrogen to form a compound of formula (I) in which R2 is a fluorenyl group of the formula -CORa (wherein it is an alkyl group or a phenyl group). Or k2 is an acetoxane carbonyl group of the formula -CO (CH2) nCOCH3. (Where n = Bu 3) a compound of formula (I). Printed in a preferred embodiment by the Consumers' Cooperative of the Bureau of Standards and Standards of the Ministry of Economic Affairs, the formula (I) alkyl carbamate derivative of formula (I) in which R2 generated in step (b) is hydrogen is reacted with an acid anhydride to synthesize 0-fluorene. The compound of formula (I), wherein the acid anhydride is, for example, acetic anhydride, acetic acid acetic anhydride, acetic acid propionic acid anhydride, glutaric acid anhydride, succinic acid anhydride, and the like. Imine (DCC), metal entertainments (such as sodium methyloxide, sodium ethoxylate, potassium third butoxide, and the like) and organic bases (such as triethylamine, N, N-diethylaniline, 4- In the presence of dimethylamine 9 and the like, it is performed in a solvent at a temperature of -5 to 1000 ° C for one hour to 4 days. The solvent is pyridine, dimethylformamide and diamine. Methyl sulfene, diglyme, and the like α are preferred. The reaction is performed in the presence of DDC, in p-pyridine, and at room temperature with 4-dimethylamino p-pyridine. -41-The size of this paper is applicable to the national standard (CNS) 6 4 specifications (210 × 297 cm) 434225 A7 B7 5. The invention description (39) is better In a specific embodiment, it is in a solvent, in the presence of an acid or a base, at a temperature of 0 to 150 ° C, and the ammonium chloride (acetamidine gaseous, ethylammonium chloride, ethylammonium chloride) Compounds, acetobutyl butyrate gas and the like) are reacted for 20 minutes to two days to form a compound of the formula (I) which has been halogenated. The acid is acetic acid, hydrogen acid, argon bromide, p-toluenesulfonic acid and Similarly, the test is for metal hydroxides such as sodium methyloxide, sodium ethoxylate, potassium tertiary butoxide, and the like, and organic bases such as triethylamine, n, n-diethylaniline, and 4-dimethylamine. Aminopyridine. The solvents are acetic acid, benzene, toluene, dioxane, diglyme, dimethylamidine, dimethylsulfinium, and the like. After the reaction is completed, it will come soon The mixture is poured into water to neutralize it with a dilute acid, such as acetic acid, hydrogen acid, sulfuric acid, and the like. The santin product is collected by filtration and then purified by recrystallization or chromatography. If no precipitated product is seen after neutralization 'Extract the mixture with organic solvents, such as chloroform, dichloromethane, or ethyl acetate and the like Extraction. The product is obtained by crystallization or chromatographic analysis. Most of the intermediates of formula (II) formed in step (b) are novel compounds. Therefore, the present invention provides a novel compound of formula () j) in another aspect. ---- Ίΐτ-Τ ---- Λ-(Please read the note ^^ on the back before filling out this page) DuPont Printing, Staff Consumption Cooperation, Central Standards Bureau, Ministry of Economic Affairs -42- This paper standard applies to Chinese national standards ( CNS) A4 specifications (210X297 mm) 434225 Α7 B7 V. Description of the invention (4〇)

.R3 --------- P— V 1 (Please read the notes on the back before filling this page) The prerequisite is that at least one of R3 and R4 is not hydrogen; and its pharmaceutically acceptable salt. For the purpose of illustration, the compounds of the novel formula (Z) of the present invention may be selected from (but not limited to) the compounds shown below; 3- (4-fluorenylacridin-9-yl) amino-5-hydroxymethylaniline; 3- (4-nitroacridin-9-yl) amino-5-hydroxymethylaniline; 3- (4-methylaminoacridin-9-yl) amino-5-hydroxymethylaniline; 3 · (4-N, N -Diamidoaminoacridin-9-yl) amino-5-hydroxymethylaniline; 3- (4-methoxycarbonylacridin-9-yl) amino-5-hydroxy Methylaniline; 3- (4-methylaminecarbonylacridin-9-yl) amino-5-hydroxyfluorenylaniline; j- (4-N, N-dimethylamine strict group σ ) Cavity 1-yl-5- via methylaniline; 3- (4-methoxyacridin-9-yl) amino-5-hydroxymethylaniline; 3- (4-N, N-dimethylaminecarbonyl -5 -Methoxyacridin-9-yl) amino group, 5, super 43- This paper size is applicable to Chinese National Standard (CNS) A4 size (210X297 mm) Ρ1Τ Employees' Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs print 434225 A7 B7 V. Description of the invention (41) Methylaniline; 3- (acridin-9-yl) amino-5_acetamidomethylaniline; 3- (4-methylaminecarbonylacridin-9-yl) Amino-5-acetamidoaniline ; 3- (4, methylaminocarbonyl-5 -methylacridin-9-yl) amino-5 -ethoxyoxanylaniline; and 3- (4-methylaminocarbonyl-5-methoxyacridine -9-yl) amino-5-acetamidomethylaniline. As shown in Tables 1 and 2 below, the compounds of formula (I) are pharmaceutically active. Based on the structural similarity, the compound of formula (11) as defined above is also pharmaceutically active. Because of this, the present invention further provides a pharmaceutical composition containing an effective amount of a compound of formula (I) as an active ingredient (please read the precautions on the back before filling this page) NHCOOR1

The paper scale is applicable to the Chinese National Standard (CNS) A4 specification (210X297 mm) ^ 3422i A7 B7 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of invention (42) R2 is hydrogen Fluorenyl, where 11 < 1 is (: |-<: 6 alkyl or phenyl; or ethanoylcarbonyl with -CO (CH2) nCOCH3, where n = 1 to 3; and R3 and R4 are acridine Substituents at different positions on the ring (ie, C-1'-C-8 '), and R4 may be the same or different, and each represents: ammonia;

Ci-C6 alkyl; CVC6 alkoxy; Nitro: • Amine with formula -NR3Re, where and Re can be the same or different, each representing hydrogen or CkG alkyl; Amine alkyl with formula -NHCCHdnNRdR6, where And Re can be the same or different, and they each represent hydrogen, CVQ alkyl, hydroxyalkyl having the formula-(CH2) nOH, where n = 1 to 3, or ^ -alkylnan; alkylamine carbonyl with -CONHRf, Where Rf is CVC6 alkyl; alkylamine alkylamine carbonyl of formula -CONH (CH2) nNRsRh, where n = L · 5, and R8 and Rh may be the same or different, and each represents hydrogen, (^-(^ alkyl or Nitro; halogen group: a hydroxyalkyl group of the formula-(CH2) nOH, where n = 1 to 3; a carbamate group of the formula -CH2CONHRf, where Rf is as previously defined; a formula of -CHsOCOK / Alkyloxymethyl, where Rf is as previously defined; with the formula -S〇3R ^ Therefore pit vinegar 'where Rf is as previously defined; -45- This paper rule is applicable to China National Standards (CNS) A4 Specifications (210X297mm) " " -------- ^}-install --------;-order ------------ (Please read the precautions on the back before filling in this (Page) 434225 A7 ~ ---------- 87 V. Description of the invention (along), with formula _SC ^ Burn the base, where Rf is as previously defined: (Please read the notes on the back before filling out this page) and its pharmaceutically acceptable salts; and its pharmacologically acceptable carrier. Furthermore, the present invention also provides a pharmaceutical combination Substance containing an effective amount of a '(π) compound as an active ingredient

(Π) wherein R3 and R4 are as defined above; a prerequisite is that at least one of 圮 and R4 is not hydrogen; and a pharmaceutically acceptable salt thereof; and a pharmacologically acceptable carrier thereof. The “effective amount” of printed products of the Consumer Cooperatives of the Central Bureau of Standards of the Ministry of Economic Affairs, also referred to as “effective amount”, refers to the amount of compounds effective to produce the expected pharmacological effects. In particular, the effect is to inhibit the growth of tumor cells. Preferably, the dosage is between 1 and 500 mg / kg. 3, preferably, the compound is y for ethyl, and R2, R3, and M are hydrogen. ) Is CONHCH3, and R4 is (C5,) is a compound of formula ⑴ for CH3. "Mathematically acceptable carrier" as referred to herein includes any standard pharmacological load. ) A4 grid (210X297 mm)

43422S Printed by the Central Bureau of the Ministry of Economic Affairs and the Consumer Cooperatives Α7 Β7 V. Description of the Invention (44) Such as sterilization solution, spin, coated tablets and capsules. Generally, these carriers contain excipients such as starch 'milk powder, sugar, certain types of clay, animal gum, stearic acid, talc, vegetable fats or oils, gums, glycerol, or other known excipients Shape agent. These carriers may also include flavoring agents and pigment additives ' or other ingredients, such as compositions that increase solubility. Compositions that increase solubility include, but are not limited to, compounds that can bind to the hydrophobic site of the requested compound. In particular, 'examples of suitable formulations include Emulplior (which is a water-miscible non-toxic polyoxyethylated fatty acid that can be diluted to 1: 1 with sterile water or sterile physiological saline solution), and polyethylene Base Pyridone. Compositions containing such carriers can be prepared by conventional methods. The pharmaceutical composition of the present invention can be administered by a variety of routes, including but not limited to oral, intravenous, intramuscular, and subcutaneous injection. The dosage form, route, amount and frequency of application will vary from case to case 'depending on the carrier used and the expected results. However, these variables can be easily determined by the skilled person. The following examples are provided to assist in understanding the present invention. These examples are not intended to (and should not be considered as possible to) limit the inventions defined in the patent application below. Example 1 Gently refluxing a known compound containing 4 drops of dimethylformamide 4-methyl-acridin-9-one (3-4 grams, 12 mmoles, according to the foregoing Denny et al., J. Med. Chem. 1987, 30: 658 (prepared as described in) and sulfite gas (20 ml) > Kun compound for 40 minutes. The mixture was concentrated to a minimum volume, diluted with toluene, and evaporated to dryness. The residue was dissolved in dichloromethane (200 ml), poured into an excessive amount of a methylamine aqueous solution (40%, 20 ml), and stirred vigorously for 10 minutes. Separation-47- This paper bears the Chinese National Standard (CNS) A4 specification (2) 0 × 297 public envy (read the precautions on the back and then fill out this page) Install 434aa§ A7 B7 V. Description of the invention (45) (Please read the precautions on the back before filling in this education) Organic layer 'Rinse with water (30 ml x 3), dry (Na2s〇4), and evaporate to dryness, get 9-Ga-5. 曱 基 _4_ 甲Aminocarbonylacridin-9_one (35 g) was directly condensed with 3,5-diamino-5-hydroxymethylaniline dihydrochloride without further purification (Example 2). Example 2 'Methylmorpholine (4 29 ml, 39 mmol) was added dropwise to an .3,5-diaminostilcohydrogenate (274 g, n mmol) in an ice bath. ) In a suspension in CHCh / EtOH (v / v, 1: 3), stir for one hour. 3 The above (Example 1) is crude 9-gas-5 -methyl_4-methylaminecarbonylacridine-9_ A solution of ketone (3.52 g, .13 mmol) in CHC13 (15 ml) was added to the mixture, and stirred for another four hours. The solid product was collected by filtration. The filter cake was thoroughly washed with CHC13, and recrystallized with MeOH to obtain 3.90 g (78%) of 3- (5-methyl-4-methylaminocarbonylacridin-9-yl) amino-5_hydroxymethylaniline , Melting point 275_278 ° C (decomposition). lH-NMR (DMSO-56): 2.83 (3H, s? CH3)? 3.11 (3H, s, NHCH3), 4.54 (2H, s, CH2), 5.50 (1H, br, interchangeable "〇H) '6.65 (2H, br, NH2) 5 6.64, 6.67A 6.82% 1H, s, ArH), 7.52 ^ 7.67 Μ, 1H, t, printed by the Shellfish Consumer Cooperative of the Central Bureau of Standardization of the Ministry of Economic Affairs

ArH), 8_02, 8.26, 8.59 and 8.67 (1H, d, ArH each), 9_78 and 11.92 (1H, br, NH each). C15HuN03 theory 値: C, 71.14; Η, 4.38: N, 5.50; Experiment 値: C, 71.25; H, 4.22; N, 8.12. According to a similar method, a 3- (acridin-9-yl) amino-5-methylaniline derivative substituted with an acridine ring as shown below is prepared: 3- (acridin-9-yl) amino- 5 -hydroxymethylaniline; 3- (4-methylacridin-9-yl) amino-5-hydroxymethylaniline; -48- SS shanghai standard (Nor) 8 4 specifications (210 father 297 male (%) 434221 A7 B7 Printed by the Shellfish Consumer Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs 5. Description of the invention (46) 3-(4-nitroacridin-9 -yl) amino-5 -hydroxymethylaniline; 3- ( 4-methylaminoacridin-9-yl) amino-5-hydroxymethylaniline; 3- (4-N, N-dimethylaminoacridin-9-yl) amino-5-hydroxymethylaniline ; 3- (4-methoxycarbonylacridin-9-yl) amino-5-hydroxymethylaniline; 3- (4-methylaminocarbonylacridin-9-yl) amino-5-hydroxymethylaniline ; 3- (4-N, N-dimethylaminocarbonylacridin-9-yl) amino-5-hydroxymethylaniline; 3- (4-methoxyacridin-9-yl) amino-5 -Hydroxymethylaniline; 3- (4-N, N-dimethylaminecarbonyl-5 -methoxyacridin-9-yl) amino-5-hydroxymethylaniline; '3- (acridine-9 -Yl) amino-5-acetamidomethylaniline; 3- (4-methylaminocarbonylacridin-9-yl) amino-5-acetamidomethylbenzene Amines; 3- (4-methylaminocarbonyl-5-methylacridin-9-yl) amino-5, acetoxymethylaniline; and 3- (4-methylaminocarbonyl-5-methoxy Acridine-9-yl) amino-5-acetamidoxymethylaniline. Example 3 Ethyl chloroarsinate (· 3.24 g, 30 mmol) was added dropwise to a 3- (acridin-9-yl) group containing pyridine (3.2 ml, 40 mmol) in an ice bath. The solution of amine-5-hydroxymethylaniline (6.30 g, 20 mmol) in 80 ml of dimethylformamide (DMF) was stirred for 15 minutes, and then evaporated to dryness in the air. The residue was chromatographed on a silica gel column (5x30 cm). The impurities were eluted with CHC13, and then the product was eluted with CHCl3 / MeOH (10: 1, v / v). Collect the eluate containing the product, concentrate it, and crystallize the residue with EtOH to obtain 6.32 -49- This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) ------ ---- --- ο Equipment ----- ij ---- P-(Please read the precautions on the back before filling this page) 434226 Printed by the Consumer Standards Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs A7 B7 V. Invention Description (47 ) f g (82%) of ethyl N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylaminoacetate, melting point 226-228 ° C (decomposition). lH-NMR (DMSO-66): 1.06 (H, s, j = 7.0 Hz, CH3), 4.10 (2H, q, J = 7.0 Hz, CH2), 4.45 (2H, s, CH2), 5.35 (1H, br; OH), 6.97 (1H, s, ArH), 7.45-7.51 (4H, m, ArH)? 8.01 (2H, m; ArH), 8.10 (2H, d, J = 7_5 Hz), 8.27 (2H, d, J = 8.79 Hz), 9.91 (1H, s, exchangeable, NH), 11.91 (1H, br, NH). The theory of C23H21N3O3 is: C, 71.30; H, 5.46; N, 10.85; the experiment is: c, 71.42; H, 5.38; N, 10.69 ° According to the same method, make 3- (5-methyl _4_methylaminocarbonylacridinyl) amino-5-hydroxymethylaniline (732 mg, 2 mmol) with ethyl formate, 596 mg (65%) of N- [3- (5 -Methyl-4-methylaminecarbonylazine-9-yl) phenylcarbamate, m.p. 252-2531 (decomposed). ^ -NMR (DMSO-56): 1.43 (3H, t, J = 7.2 Hz), 2.93 (3H, s, CH3), 3.17 (3H, s, NHCH3), 4.31 (2H, q, J = 7.2 Hz, CH2), 4.64 (2H, s, CH2), 5.52 (1H3 br, OH), 7.14 (1H, ArH), 7.55-7.78 (4H, m, ArH), 8_10, 8.33, 8.68, and 8.87 (each 111, (1, 8 1'11), 9.80, 10.11, and 11.57 (each 1H, br, exchangeable, NH). C26H26N404 theoretical 値: C, 68.11; H, 5.72; N, 12.22; experimental 値: C, 68.23; H, 5.79; N, 12.14. According to the same method, the following alkyl carbamate derivative was prepared: N_ [3_ (acridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate ethyl ester; N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isopropyl ester; N- [3- (acridin-9-yl) amino-5-hydroxymethyl Phenyl] phenylcarbamate; N- [3- (4-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate ethyl-50- This paper applies Chinese national standards (CNS) A4 specification (210X297mm) '' Install Γ ~ Order ~ .. {Please read the ii. Notice on the back before filling in this page)

43422S Printed by A7 B7 of the Consumers' Cooperative of the Central Bureau of Standards of the Ministry of Economic Affairs V. Description of the invention Ethyl] phenylcarbamate; N- [3- (4-aminoacridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamate; N- [3- (4- Methylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate ethyl acetate; N- [3- (4-N, N-dimethylaminoacridin-9-yl) amine Ethyl-5-hydroxymethyl] benzyl urethane; N: [3- (4-methoxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacetate; N- [3- (4-methylaminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacetic acid ethyl alcohol; N- [3- (4-N, N-dimethylamine Carbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-methoxyacridin-9-yl) amino-5-hydroxymethyl ] Phenylcarbamic acid ethyl ester; N- [3- (4-N, N-Diamidocarbonyl-5-methoxyacridin-9-yl) amino-5 -hydroxymethyl] phenyl Ethyl carbamate; N- [3- (acridin-9-yl) amino-5-acetamidomethyl] phenylcarbamate; N- [3- (4-methylaminocarbonylacridine- 9-yl) amino-5-acetamidomethyl] phenylcarbamate Ester; N- [3- (4-methylaminocarbonyl-5 -methylacridin-9-.yl) amino-5 -acetamidine-51-This paper is applicable to Ningguo National Standard {CNS) A4 Specifications (210X 297mm) -------- ηί ------ ^ Order I .---- < f (Please read the notes on the back before filling this page) 43422 & A7 B7 V. Description of the Invention (49) Methyl] phenylcarbamate; and N- [3- (4-methylaminocarbonyl-5-methoxyacridin-9-yl) amino-5-ethyl alcohol Oxymethyl] phenylcarbamate. Pharmacological experiments evaluate the N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylamine phosphonate derivative of the present invention against human leukemia HL-60 cells and 833K tumor cells in vitro Cytotoxicity of growth and N- [3-(acridin-9-yl) amino-5-canthyl] phenylcarbamate in mice bearing Sarcoma 180 and Lewis lung cancer tumors effect. The 3- (acridin-9-yl) amino-5-hydroxymethylaniline (AHMA) was also evaluated for comparison. The results are shown in the table below. 1 pack Order 1 »(Please read the notes on the back before filling in this page)

Printed by the Consumer Affairs Cooperative of the China Liquor Bureau of the Ministry of Economic Affairs of the People's Republic of China. $ 1 Table 1. Anti-human leukemia HL-60 cells and 833K tumor cell growth in vitro. Cytotoxicity. Compound R1 R2 4'-R3 5_-R4 IC50 Inhibiting Cell Growth HL-60 833K (μΜ) l (AHMA) Η HHH 0.025 — 2 COOEt HHH 0.016 0.020 3 COOCH2CKMe2 HHH 0.018 0.021 4 Η H CONHMe Me 0.144 0.244 5 COOEt H CONHMe Me 0.083 0.034 -52- The size of this paper is applicable to the Chinese National Standard (CNS) A4 specification (210 × 297 mm) 434225 A7 B7 V. Description of the invention (50) Table 2 lists the tumors containing Sarcoma 180 and Louis ’lung cancer. B6D2Fi mice chemostatic stasis effect tumor dose (mg / kg) average weight change mean tumor volume change (T / C) Day 7 Day 10 Day 7 Day 10 Sarcoma 180 Control group -0.5 +0.7 1.00 1.00 3.0 -2.0 -0.7 1.24 1.21 5.0 -2.6 +1.0 0.06 0.63 7.0 -3.4 -0.1 0.22 < 0.0 lb Lewis lung cancer control group -1 -0.1 1 1 3.0 -2.3 -1.3 0.8 0.63 6.0 -3 -2.6 • 0.44 0.37 8.0 C -3.6 — 0.21 — ------- Λ— 装 ----- 1 Order—Γ I i (Please read the notes on the back before filling out this page) The policy of employee consumer cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs a Sarcoma 180 (3 x 106 cells) was inoculated subcutaneously (sc) on day 0. Treatment started on day 1 by intraperitoneal injection (i.p.) four times daily for five days. The control group consisted of four mice, two at each dose. The lung cancer (4 x 206 cells) was inoculated subcutaneously two days (-2 days) before the previous test. Treatment started on day 1 by intraperitoneal injection four times a day for five days. A total of four mice in the control group, three at each dose, were measured for tumor volume on day 7 and day 10. b No tumor can be detected. c One mouse died on day 8 and two mice died on day 9. Obviously, AHMA has effective anti-leukemia and growth of several solid tumors in vitro and in vivo, and has a long half-life. The compound of the present invention is more than -53- This paper is applicable to Chinese National Standard (CNS) A4 (210X297) (%) 43422S A7 B7 5. Description of the invention (51) Its AHMA derivative precursor is more effective. __ -Article J (Please read the precautions on the back before filling out this page) I Ding- ° Printed by the Consumers' Cooperatives of the China Standards Bureau of the Ministry of Economic Affairs 54 This paper size applies to the Chinese National Standard (CNS) A4 (210 X 297) %)

43422 § Supplementary explanation of Patent Application No. S5102887 in May of that year) Example: A gas-AΗΜΑ hydrochloride (5) 4-methoxymorpholine was added dropwise to the 4-methylmorpholine in an ice bath (2.74 g, 13 mmol) in a suspension of CHCl3 / EtOH (I: 3 v / v). After stirring for 1 hour, the crude 9-chloro-4-methoxyacridine (made from 4-methoxy-9 (10 甲) -acridone, 2.83 g, 13 mmol) was added at 0 °. ) Of CHC13 (15 ml) was added dropwise to the mixture and stirred vigorously for 4 hours. The crude solid product was collected by filtration, washed with EtOH, and then recrystallized from MeOH to give (5): 2.02 g (70%); melting point 247 -8 ° C NMR (DMSO-d6) (5 to .16 (1H, s, OMe), 4.38 and (2H, s, CH2) '5.20 (1H, br, OH), 5.82 (2H, br, NH2), 6.46, 6.51 and 6.64 (1H's' 3 x ArH each), 7.41 (1H, t, J = 8, 7 Hz, ArH), 7.46 (1H, t, J = 8.7 Hz, ArH) , 7.96 (1H, t, J = 8.0 Hz, ArH), 8.27 and 8_37 (1H, d, J = 8.6 Hz, 2 x ArH) '11.33 (1H, brs, NH). Analysis (C2lHl9N302 · 2HC1) C , Η, N. The following compounds were prepared using the same procedure as in synthesis (5): 4'-methylazine-AHMA hydrochloride ⑹ by 4 · fluorenyl-9 (10H) -acridone (1.20 g, 5.70 mmol) Ear) and 4-methylmorpholine (1.21 g '5. ^ 0 mmol): Synthesis: 1.67 g (88%): melting point 264-5 ° C; NMR (〇MSO-d0) < 5 2.78 ( 1H 's, Me), 4.37 ( 2H, s, CH2), 5.18 (1H, br'oH), 5.50 (2H 'br'NH2), 6.39, 6.46, and 6'59 (each 1H, s, 3 x ArH), 7.37 (1H, t' J = 8.〇Hz 'ArH)'

1! * H WCK SI.S DOC

43422S 7.43 (1H, t, J = 8.0 Hz, ArH), 7.86 (1H, d, J = 8.0 Hz, ArH), 7.96 (1H, t, J = 8.0 Hz, ArH), 8.23 and 8.26 (each 1H, d, J = 8.8 Hz, 2 x ArH), 8.41 (1H, d, J = 8.0 Hz, ArH), 11.33 (1H, brs, NH). Analysis of (C2 [Hl9N30. HC1. H20) C, H, N. Each formamidine-AHMA HO consists of crude 9-chloroacridin-4-methylcarboxamidine (3.64 g, 13 mmol) and 4-oxomorpholine (2.744 g, 13 mmol) Ear) synthesis: yield 2.86 g (59%); melting point 275-6 ° C; 'Η NMR (DMSO-d6) δ 2.96 (3H, s, NHMe), 4.38 (2Η, s, CH2), 5.21 ( 1Η, br, OH), 5.80 (2Η, br, NH2), 6.46, 6.52, and 6.64 (each 1H, s, 3 x ArH) '6.19 (2H, s, 2 x ArH), 7.44 (1H, m, ArH) ) '7.51 (1H' m 'ArH)' 7.96 (1H, m, Alm), 8.11 (1H, m, ArH), 8.26 (1H, m, ArH), 8.49 (2H, br, ArH), 9_34 and 11 '63 (1H, brs, 2 x NH each). Analysis ((: 22 spitting called 02 · HC! · 1/2 H20) C, Η, N. 41-Dimethylamine ethyl chemoamine-AHMA (8) bitten by crude 9-rat pf- Synthesis of 4-monomethylaminoethylcarboxamide (2.05 g, 6.57 mmol) and 4-methoxymorpholine (1.39 g, 6.57 mmol): yield 1.83 g (65%); melting point 82- 3 ° C; 屮 NMR (DMSO-d6) 6 2.35 (6H, s, NMe2), 3.47 and 3.62 (each 2H, brs, 2 X CH2), 4.29 (2H, s, CH2), 5.21 (1H, br, OH), 5.52 (2H, br, NH2), 5.90 (IH, s, ArH), 6.19 (2H, s, 2 x-ArH) * 7.45 (1H, t, J = 8.0 Hz, Ai.H), 7.51 (1H, t, J = 8.0 Hz, ArH) '7.87 (1H, d' J = 8_0 Hz, ArH), 8.14 (1H, d, J = 8.8 Hz, ArH), 8,20 (1H, d, J = 8.8 Hz, ArH), 8.37 (1H, d, J = 8_8 Hz, ArH), 8.66 (1H, d, J = 8.0 Hz,

1 TVPt UCKSLSB \ 4: g33.ISUPD〇C

ArH), 9,23 (1H, br, NH), 12,23 (1H, brs, NH). Analysis (C25H27N502 · HC1. H20) C, H, N. Nitro-AHMA hydrochloride (9) consists of 4-nitro-9 (10H) -acridone (4.8 g, 20.0 mmol) and 4-methoxymorpholine (4.22 g, 20.0 mmol) )synthesis. The crude product (5.63 g, 81%) of TLC (Si02, CHCl3 / MeOH, 10: 1 v / v) showed a mixture of two main compounds (R produced 0.6 and 0.3), which are due to their poor solubility in organic solvents. Not separated. The mixture was used directly in the next reaction without further purification. Small amounts of compounds with low values are isolated by column chromatography (Si02, CHCl3 / MeOH, 10: 1 v / v) and then treated with IN HC1 to form the hydrochloride salt and crystallize from EtOH: Oak Point 219- 20 ° C: NMR (DMSO-d6) 54.50 (2H, s, CH2), 5.21 (1H, br, OH), 6.09 (2H 'br, NH2), 7.36 (1H, s' ArH), 7.39 (2H, s, 2 x ArH) 1 7.50 (1H 5 t 1 J = 8.0 Hz * ArH) 1 7.58 (1H > t 'J—8.0 Hz i AtH), 8.02 (1H, d, J = 8.0 Hz, ArH), 8.25 (1H, d, J = 8.0 H2, ArH), 8.37 (1H, d, J = 8.8 Hz, ArH), 8.81 (1H, d, J = 8.8 Hz, ArH) '8.86 (1H, d, "HO Hz 'ArH), 9.36 (1H, br, NH). Split (C20H16N403. HCI. H20) C, H, N. In a similar manner, compounds (10)-(12): 4'-1.-AΗΜΑα〇) were synthesized and purified as described in (9) from 4-fluoro-9 (1〇Η)-. Acridinone (2.13 g, 10.0 mmol) and 4-methoxymorpholine (2.11 g'10.0 mmol) were synthesized. Crude product yield 2.40 g, 76%: A small amount of crude product was purified by silica gel column chromatography (CHC 丨 3 / MeOH, 20: 1 v / v) to obtain pure (10), and analyzed: melting point> 280 ° C; lH NMR (DMSOd6) 54.3l (2H 'd' J = 4.2 Hz 'CH2)' 5.01 (1H, t, J = 4.2 Hz, OH), 5.98,

, r, -n. VW K SLS'n 4; 9J3-1SUPD0C

43422S 6.14, 6.27 (1H, s' 3 x ArH each), 7.12 (2H, m, 2 x ArH), 7.24 (2H, m, 2 x ArH), 7.37 (2H, brs, NH2), 7.56, 7.7 7.94 and 8.ΐ〇 (1H each, m '4 x ArH). Analysis (C20H16FN3O. H20) C, H, N. Chloro-AHMA hydrochloride Π1) is derived from 4-chloro-9 (10H) -acridone (2.17 g, 1.00 mmol) and 4-oxomorpholine (2.11 g, 10.0 mmol) Mol) synthetic. Crude product yielded 2 42 g of 72%. (Ll) -HCl salt: melting point 232-4 ° C; NMR (DMSO-d6) 5 4.49 (2H, s, CH2), 5.21 (1H, br, OH), 6.62 (2H, br, NH2), 7. · 48 (3H, s' 3 x ArH), 7.51 (1H, t, J = 8.0 Hz, ΑιΉ), 7.55 (1H, t, J = 8.0 Hz, ArH), 8.03 (1H, d, J = 8.0 Hz, ArH) '8.21 (1H, d, J = 8.0 Hz, ArH), 8.47 (1H, d, J = 8.8 Hz, ArH), 8.55 (1H, d' J = 8.8 Hz, ArH), 8.60 (1H, d , J = 8.0 Hz, ArH), 9.16 (1H, br, NH). Analysis (C20H16CIN3O · HC1. H20) C, H, N. Bromo-AHMA hydrochloride (II2) is derived from 4-bromo-9 (10H) -acridone (2.74 g, 10,0 mmol) and 4-methoxymorpholine (2.11 g, 10.0 mmol) synthesis. The crude product yielded 2.97 g, 78%. (12) -HC1 salt: melting point> 280 ° C; 'H NMR (DMSO-d6) M.46 (2H, s, CH2), 5-18 (1H, br, OH), 6.62 (2H, br, NH2) , 7.10 UH, s, ArH) '7.22 (2H, s, 2 x ArH), 7.39 (1H, t, J = 8.0 Hz, ArH), 7'50 (1H, t, J = 8.0 Hz, ArH), 7.96 (1H, d, J = 8, 0 Hz, ArH), 8.30 (1H, d, J = 8.0 Hz, ArH), 8.32 (1H, d, J = 8.8 Hz, ArH), 8.47-8, 50 ( 2H, m, 2 x ArH), 8.98 (1H, br, NH). (C20H16BrN3O.HQ. 2H20) C, H, N. iHJl group-5L Memum Sife Ammine-AHMA hydrochloride (13) is from crude 4-methoxy-9-chlorine 1, P | :, WSLS B 4: q; 3-lSUP DOC -4 stomach 434aa § Synthesis of acridine-5-methylcarboxamide (5.55 g, 18.5 mmol) and 4-methoxymorpholine (3.91 g, 18.5 mmol): yield 4.40 g (60%); melting point 222 -3 ° C; NMR (DMS 0-d6) 52.82 (3H, s, NHMe), 4.13 (3H, s, OMe), 4'38 (2H, s, CH2), 5.20 (1H, br, OH), 5.80 (2H, br, NH2), 6.45, 6_49, and 6.63 (1H, s, 3 x ArH each), 7.36 (1H, t, J = 8.0 Hz, ArH), 7.51 (2H, m, 2 x ArH) ), 7.80 (1H, d, J = 8.0 Hz, ArH), 8.51 (1H, d, J = 8.0 Hz, ArH), 8.56 (1H, d, J = 8.0 Hz, ArH), 9.43 (1H, br, NH). Analysis (C23H22N403 'HC1. 1/2 H20) C, Η, N. 41-methylamino-5'-dimethylaminoethylamidoamino-AHMA (14) is a crude 4-methoxy-9-chloroacridan-5-dimethylaminoethylcarboxycarbamate Amine (1.21 g, 3.71 mmol) and 4-methoxymorpholine (0.783 g, 371 mmol) synthesis: yield 0.904 g (52%); melting point > 280 "C; 'H NMR ( DMSO-d6) < 5 2.87 (6H, s, NMe2), 3.41 and 3.82 (each 2H, brs, 2 X CH2), 4.15 (3H, s, OMe), 4,46 (2H's, CH2), 5.20 (1H, br, OH), 7.13 (1H, s, ArH), 7.19 (2H, s, 2 x ArH), 7.43 (1H, t, J = 8.0 Hz, ArH), 7.60 (2H, m, 2 x ArH), 7.83 (1H, d, j = 8.0 Hz, ArH), 8.60 (1H, d, J = 8-0 Hz, ArH), 8,94 (1H, d, J = 8.0 Hz * ArH), 10.00 (1H, br, NH), 10,08 (1H, bfs, NH), 12_09 (1H, br, NH). Analysis (C26H29N503 · 2HCI. 10 1/2 H20) C, Η, N. ^ 4-Methyl_5'_Methylsulfenylamino_AHMA hydrochloride (5) is from crude 4-methyl-9-chloroacridin-5-methylcarboxamide (3.58 g * 13 mmol Mol) and 'methoxy?' Hugh (2.74 g, 13 mmol) synthesis: 4.80 g (95%), melting point 275-7 ° C; iHNMRCDMSO-c ^) ^

[TVIJi: '.vc k SL.S B.42933-ίSUP DOC 4 pieces 2 s, 2.83 (3H, s, Me)' 3.11 (3H, s, NHMe), 4.54 (2H, s, CH2), 5.50 dH 'br, OH), 6.65 (2H, br, NH2), 6.64 * 6.67 and 6.82 (1H, s, 3 x ArH each), 7.52 (1H, t, J = 8.0 Hz, ArH) , 7.67 (1H, t, J = 8.0, ArH), 8.02, 826, and 8.67 (each 1H, d, J = 8.0 Hz, ArH), 9,78, and U_92 (each 1H, br, NH). (C23H22N402. HO 2 3/4 H20) C 'C, N. Dimethyl amine, ethamidine-AHMA Π6) #from crude S'-fluorenyl-9-chloroacridan, 5-dimethylamine ethylcarboxamide (1.80 g, 6.0 mmol) and 4-Methoxymorpholine (U26 g, 6.0 mmol) Synthesis: 0.847 g (55%); melting point 210-3 ° C dec; 4 NMR (DMSO-d6) 5 2.78 (3H, s, Me) '2,8 · 7 (6H, s, NHMe2), 3.42 and 3.84 (each 2H' brs, 2 x CH2), 4.46 (2H, s, CH2), 5 * 20 (1H, br, OH), 7.35 , 7.37 and 7.40 (1H, s, 3 x Ai.H each) * 7.62 (1H, i, J = 8.0 Hz, ArH) '7.98 (1H, d, J = 8.0 Hz, ArH)' 8.19 (1H , D, J = 8.0 Hz, ArH), 8.65 (1H, d, J = 8.0 Hz, ArH), 8.95 (IH, d 'J = 8.0 Hz, ArH), 10.10 (1H, br, NH), 10.08 ( 1H, brs, NFi) '10.80 (1H' br, NH). (C26H29N402. HCI) C, H, N. Carbamate Methyl n 7. Add methyl aquamate (0-58 g, 5.4 mmol) to AHMA (1.87 g '<50 mmol) anhydrous DMF (50 g Liters) of the solution, then the mixture was stirred at room temperature for 15 minutes, and evaporated to dryness in vacuo. The residue was co-evaporated with EtOH for several hours, and chromatographed on silica gel (5 X 50 cm). The impurities were eluted with CHCb, and the product was eluted with CHCb / MeOH (10: 1 v / v). Collect fractions containing product, concentrate and

1. WCK SLSiJ Jl}} 3-lSUP.DOC 43422 ^ Recrystallized twice from DMF / EtOH to obtain (17): 1_08 g (64%); melting point 273-4 ℃; 'H NMR (DMSO- d6) 53.64 (3H, s, Me) '4.45 (2H, s, CH,), 5.32 (1H, br, 0H), 7.44 (2H, s, 2 x ArH), 7.45 (2H, d, J = 7, 3 Hz, Ar), 7.49 (2H 'd, J = 5.6 Hz, 2 x ArH), 8.00 (2H, t, J = 7 8 Hz' 2 x ArH), 8.09 (2H, d 'J = 8.4 Hz, 2 x ArH), 8.26 (2H, d, J = 8.8 Hz '2 x ArH)' 9.91 and 11.49 (each 1H, brs, 2 x NH). Analyze (C22H19N3O3. HQ · H20) C, Η, N β Follow the same steps as in (17) to prepare the following compounds: ΑΗΜΑ-aminoethyl ethyl ester 8) is derived from ΑΜΜΑ (6.30 g, 20 mmol) Synthesis of ethyl acetate (3.42 g, 30.0 mmol): yield 6.32 g (82%): melting point 226-8 &quot; C dec; 'H NMR (DMSO-d6) δ 1.06 (3H * t &gt; J = 7.0 Hz &gt; Me) 1 4.10 (2H, q, J = 7.0 Hz, CH2), 4.45 (2H, s, CH2), 5.35 (1H, br'OH), 6.97 (1H, s, ArH), 7.46 ( 2H, s, 2 x ArH) '. 7.48-7.51 (2H, m, 2 x ArH), 8, (M, 8.03, 8.05, and 8.07 (each 1H, d, J 2 8.0, 4 x

ArH), 8.26 (1H, d, J = 8.8 Hz, ArH), 9'91 (1H, s, NH), 11.47 (1H, brs' NH). Analytical (C23H2lN3Or HC1 · 1 1/2 H20) C, H, N. AHMA-propyl carbamate (19) is synthesized from ΑΜΜΑ (0.630 g, 20 mmol) and chlorochloroacetate (0.30 g, 2.4 mmol): yield 0.62 g (78%); melting point 208-9 C; 'H NMR (DMSO-d6) (5 0,91 (? H, t, J = 7.1 Hz, Me), 1.59-1.62 (2Η' m, CH2), 4.02 (2H, t, J = 6.4 Hz 'CH])' 4.46 (2H, s' CH2), 5.25 (1H, br, OH), 6'93 (1H, s, ArH), 7.46-7.52 (4H, m, 4 x ArH), 7.99 -8 · 03 (2H, m, 2 x ArH), 8.11-8.13 (2H, m, 2 x

S

ArH), 8.28 (1H, d, J = 8.8 Hz, ArH), 9.89 (1H, s, NH), 11,82 (1H, brs, NH). Analysis (C24H23N303. HC1. H20) C, H, N. AHMA-isobutyl carbamate hydrochloride (20) is synthesized from AΗΜΛ (0.63 g '2.0 mmol) and isobutyl chloroformate (0.41 g, 3.0 mmol): yield 0.729 g (88%); Melting point: 255-6 ° C; W NMR (DMSO-d6) (5 0.90 (6H, d, J = 7.0 Hz, 2 X Me), 1.84-1.91 (2H, m, CH), 3.84 (2H, d, J = 6.4 Hz, CH2), 4.45 (2H, s, CH2), 5.35 (1H, br, OH), 6.98 (1H, s, ArH), 7.44-7.50 (4H, m, 4 x ArH), 8.00 (2H , T, J = 8.8 Hz, 2 x ArH), 8.14 (2H, d, J = 8_8 Hz, 2 x ArH), 8.28 (2H, d, J = 8.8 Hz, 2 x ArH), 9.89 (1H, s , NH), 11.82 (1H, brs, NH). Analytical (C25H25N303- HC 1 1/2 H20) C, H, N. AHMA-carbamic acid benzyl hydrochloride (21) is from AHMA (0.63 g ' 2.0 mmol) with phenyl chloroformate (0.468 g, 3.0 mmol): yield 0.787 g (90%); melting point 228-9 ° C; '； NMR (DMSO-d6) 〇4.48 (2H &gt; s ^ CH2) &gt; 5.40 (1H-br &gt; OH), 7.02 (1H, s, ArH), 7.22 (2H, s, 2 x ArH), 7.42-7.52 (6H, m, 6 x ΑιΉ), 8.00 (2H, m, 2 x ArH), 8,07 (2H, m, 2 x ArH), 8.29 (2H, m, 2 x ArH), 10.49 (1H, brs, NH), 11.55 (1H, br, NH). Analytical (C27H21N303, HCI — 1 1/2 H20) C, hydrazone, N. AH. MA-aminocarbamate hydrochloride ( 22) Synthesized from AHMA (0.65 g, 2.0 mmol) and ethyl chloroformate (0.51 g, 3.0 mmol): yield 0.75 g (78%); melting point 214-50 ° C; 'NMR (DMSO -d6) ¢ 5 4.50 (2H-s &gt; CH2)-5.51 (2H &gt; s -CH2), 5.31 (1H, br, OH), 7.02 (1H, s, ArH), 7.37-7.77 (4H, m ,

[ΙΛ I'F. WCK SLS \ B &gt; I2933-ISL'P DOC 4 x ArH), 8.03 (2H, t, J = 8.0 Hz, 2 x ArH), 8.21 (2H, d, J = 8, 0Hz , 2 x ArH), 8.33 (2H, d, J = 8.8 Hz, ArH) '10.11 (1H, s, NH), 11.64 (1H, brs, NH). (C28H23N303. HCL · 1 1/2 H2 0) C, H, N. 4 · -formamidine-AHMA-amine formamidine ethyl ester [23] is synthesized from (5) (0.345 g '1.0 mmol) and ethyl chloroformate (0.130 g, 1.2 mmol): yield 195 mg (47%); melting point 210-2 ° C; 'H NMR (DMSO-d6) &lt; 5 1.23 (3H, t, J = 6.7 Hz, Me), 4.10 (2H, q, J = 6.7 Hz, CH2) , 4.16 (1H, s, OMe), 4.44 (2H, s, CH2), 5.28 (1H, br, OH), 6.93 (1H, s, ArH), 7.39-7.53 (4H, m, 4 x ArH), 7.54 (1H, d, J = 8.0 Hz, ArH), 7.82 (1H, d, J = 8.7 Hz, ArH), 7'92 (1H, t 'J = 8.0 Hz, ArH), 8.25 and 8J6 (1H each , D, &gt; 8.6 Hz '2 x ArH), 9_87 and 12.10 (each 1H, brs, NH). Analyze (C24H23N304 · HC1 ’H20) C, Η, N. Heart methyl-AH.MA-urethane (24) is synthesized from (6) (0.584 g, 1.5 mmol) and ethyl formate (0.195 g '1.8 mmol): Yield 0.506 mg (73 %); Melting point> 280 ° C; 'Η NMR (DMSO-d6) 〇1.22 (3H-t &gt; J = 6.8 Hz-Me) * 2.81 (3H' s 'Me)' 4_09 (2H, q, J = 6.8 Hz, CH2), 4.43, 4.44 (2H 's, CH2)' 6'92 (1H, s 'ArH), 7.38-7.49 (4H, m, 4 x ArH), 7.87 (1H, d' &gt; 6.8 Hz 'ArH), 8.01 (1H, t K8 Hz, ArH), 8J9-8.23 (2H, m, 2 x ArH), 8.46 (1H, d, J = 8.4 Hz, ArH), 9.88 (1H, brs, ΝΉ) '11_48 (1H' br 'ΝΉ). Analysis (C24h23n3 03 · HC |. I &quot; 2 H20) C, Η, N. f ^ t KSLSD ^: 9jMSUP.DOC-9-434221 Methylcarboxamido-AHMA-urethane (25) is derived from (7) (0_63 g, 2.0 mmol) and ethyl formate (0.324 G, 3.0 millimolar) Synthesis: yield 0,506 mg (73%); melting point 232-3 ° C; NMR (DMSO-d6) 5 1.28 (3H, t, J = 6.4 Hz, Me), 2.60 (3H, s , NHMe), 4.16 (2H, q, J = 6.7 Hz, CH2), 4.53 (2H, s, CH2), 5.28 (1H, br, OH), 7.01 (1H, s, ArH), 7.51-7, 60 (4H, m, 4 x ArH), 8.08 (1H, t, J = 8.0 Hz, ArH), 8.15 (1H, d, J = 8.0 Hz, ArH), 8.24 (1H, d, J = 8.0 Hz, ArH ), 8.48 (2H, d, J = 8.0 Hz, 2 x ArH), 8.93 and 9.93 (each 1H, brs, NH). Analysis (C25H24N404. HC1 · 3 1/4 H20) C, H, N. 4'-Dimethylamine ethylammonium-AHMA-urethane (26) is derived from (8) (0.215 mg, 0.5 mmol) and ethyl chloroformate (0.081 g, 0.75 mmol) ) Synthesis: Yield 0.174 mg (69%); melting point 115-7 ° C; h NMR (DMSO-d6) c5 1,23 (3H, t, J = 7.0 Hz, Me), 2.88 (6H, s, NMe2) , 3.34 and 3.S1 (each 2H, brs, 2 x CH2), 4.10 (2H, q, J = 7.0 Hz, CH2), 4.44 (2H, s, CH2), 5_38 (1H, br, OH), 6 ·% (1H, s, ArH), 7.48-7.55 (4H, m, 4 x ArH), 8.00 (1H, d, J = 8, 0 Hz, ArH), 8.19 (1H, d, J = 8.8 Hz, ArH), 8.26 (1H, d, J = 8.8 Hz, ArH), 8.52 (1H, d, J = 8.8 Hz, ArH), 8.69 (1H, d, J = 8, 0 Hz, ArH), 9.91 (1H , Br, NH), 10.65 (1H, br, NH). Analysis (C28H31N504 · HC1 · Η 20) C, Η, N. 4'-Nitro-AHMA-urethane (27) is derived from crude 4'-nitro-AHMA (9) (3.60 g, 100 mmol) and ethyl chloroformate (1.30 g, 2.0 mmol) Mol) Synthesis: yield 3.24 g (75%); melting point 180-2 ° C; NMR (DMSOd6) (5 1.22 (3H, t, J = 7.2 LTV! 1! Wt K iLSU'4: 933-ISL: P DOC -10-

Hz, Me), 4.08 (2H, q, J = 7.2 Hz, CH2), 4.41 (2H, s, CH2), 5.48 (1H, br, OH), 6.81 (1H, s, ArH), 7.30-7.38 ( 4H, m, 4 x ArH), 7.50 (1H, m, ArH) '8.07 (1H, m, ArH), 8.19 (1H, m, ArH), 8.65-8.17 (2H, m, 2 x ArH), 9.52 And 9.60 (1H, brs, NH each), 10.85 (1H, br, NH). (C23H2ON405. HCi. H20) C, H, N. Cardiofluoro-AHMA-urethane (28) is derived from crude 4, -fluoro-AHMA (10) (2.19 g, 6.0 mmol) and ethyl formate (0.78 g, 7.19 mmol) Synthesis: yield 2.19-g (90%); melting point 238-9. (:; H NMR (DMSO-d6) &lt; 5 1.23 (3H, t, J = 7.2 Hz, Me), 4.11 (2H, q, J = 7.2 Hz, CH2), 4.46 (2H, s, CH2) , 5.23 (1H, br'OH), 6.99 (1H, s, ArH), 7.36-7.52 (4H, m, 4 x ArH), 7.89-S.01 (2H, m, 2 x ArH), 8.12 (1H , D, J = 8.8 Hz, ArH), 8.27-only. 29 (2H, m, 2 x ArH), 9.91 (1H, br, NH), 12.00 (1H, brs, NH). Analysis (C23H20N3O3. HC1. 1 1 / 4H20) C, H, N. Gas-AHMA-urethane (29) is a crude 4, -chloro-AHMA (11) (1.72 g, 4.5 mmol) and ethyl chloroformate (0.586 g, 5.4 mmol) Synthesis: 1.06 g (56%); melting point 174-5 ° C; NMR (DMSO-d6) (H.24 (3H, t, J = 7.0 Hz, Me) '4.11 (2H, q, J = 7.0 Hz, CH2), 4.44 (2H, s, CH2), 5.22 (1H 'br' OH), 6.96 (1H, s, ArH), 7.41-7.49 (4H, m, 4 x ArH), 8.00 (1H, d, J = 8.8 Hz, ArH) '8.Γ9 (1H, d, J = 8.8 Hz, ArH), 8.25 (1Π, d, J = 8.8 Hz, ArH), 8.35 (1H , D, J = 8.8 Hz, ArH), 8.87 (JH 'd, J = 8.8 Hz, ArH), 9.91 (1H, br, NH), 12.00 (1H, brs, ΝΉ). Analysis (c23H20C1N3O3 · H C1. 7 H20) C, Η, N. · K SLS B 4N; 5-ISUP D0C -11- ^ 34225 i ^ -AHMA-amine aminoethyl ester DO) is a crude 4'-bromo-AHMA (12) (1_92 g, 4.5 mmol) and ethyl chloroformate (0.585 g, 5.4 mmol) Synthesis: Yield 丨. 42 g (68%); melting point 200-203 ° C; NMR (DMSO-d6) 5 1.25 (3H, t, J = 7.0 Hz 'Me), 4.11 (2H, q' J = 7.0 Hz, CH2), 4.44 (2H, s, CH2), 5.20 (1H, br'OH), 6.95 (1H 's' ArH) '7.34-7.48 (4H, m, 4 x ArH), 8.02 (1H' d, J = 8.6 Hz, ArH), 8.24 (1H, d, J = 8, 6 Hz, ArH), 8.35 (1H 'd' J = 8.8 Hz 'ArH)' 8.38 (1H, d, J = 8.8 Hz, ArH), 8.53 (1H 'd' J = 8.8 Hz 'ArH), 9.90 (1H, br, NH), 12.05 (1H, brs, NH). Analysis (C23H20BrN3O3 · HC1 · 11/2 H20) C, Η, N = 4-methyllactyl-5-methylmethyldonkey amino-AHMA-carbamic acid ethyl acetate hydrochloride (31) stick from (13) India 5 mg, 0.805 mmoles) and ethyl chloroformate (no mg, 096 mmoles) synthesis: yield 178 mg (46%); melting point 214-5 ° C; 4 NMR (DMSO-d6) &lt; 5 1.23 (3H 't, J = 7.4 Hz' Me), 2,94 (3H, s, NHMe), 4.1 (2H, q, J = 7.2 Hz 'CH2), 4.15 (3H' s, 0Me), 4 , 44 (2H, s, CH2), 5.52 (1H, br'OH), 6.96 (1H, s, ArH), 7.42 (1H, t, J = 8.0 Hz, ArH), 7.46 (2H, s, 2 x ArH), 7.52-7.58 (2H, m, 4 x ArH), 7.73 (1H, d, J = 8.8 Hz 'ArH), 8.46 (1H, d, J = 8'8 Hz, ArH), 8.55 (1H' d 'J = 7.2 Hz' ArH) '9.37 and 9'92 丨 .11 and h7i (1H, br, NH each). Analysis (C26H26N405 · HC1) C, H, N. 4'-Methoxy-5'-Dimethylamine Acetyl Residue J | Amine-AHMA-Aminomethyl Λ ester n2) White (14) (200 mg, 0.43 mmol) and ethyl formate (50 mg, 0.54 millimolar) Synthesis: Yield 103 mg (45%); melting point 220- "C; W NMR (DMSO-d6) 5 C butyl YPE WCK \ SLS \ Bvi2« 3-lSUP DOC 12.43422§ I. 23 (3H, t, J = 7.1 Hz, Me), 2.88 (6H, s, NMe2), 3.40 and 3.81 (each 2H, brs, 2 x CH2), 4.11 (2H, q, J = 7.0 Hz, CH2), 4.15 (3H, s, OMe), 4.44 (2H, s, CH2), 5.20 (1H, br, OH), 6.95 (1H, s, ArH), 7.41-7.46 (3H, m, 3 X; ArH), 7.58-7.60 (2H, m, 2 x ArH), 7.79 (1H, d, J = 8.0 Hz, ArH), 8.54 (1H, d, J = 8.0 Hz, ArH), 8.86 (1H, d, J = 8.0 Hz 'ArH), 9.88, 9.97, and 10.62 (each 1H, br, NH). Analytical calculation: C29H33N505 · HCl · 1 1/2 H20: C, 58.53; H, 6.27; N,-II. 78: C, H, N. 4. A-5'-methylcarboxamide-AHMA-urethane hydrochloride 03) is from (15) (732 mg, 2.0 mmol) and ethyl formate. Ester (239 mg, 2.2 mils) Synthesis: Yield 596 g (65%); melting point 252 -3 ° C; iHNMR (DMSO-d6) &lt; 5 1.43 (3H, t ,, J = 7.2 Hz, Me), 2.93 (3H, s, Me), 3.17 (3H, s, NHMe), 4.31 (2H * q, J = 72Hz, CH2), 4.64 (2H, s, CH2), 5.52 (lH, br, OH), 7.14 (1H, s, ArH), 7.55-7.78 (4H, m, 4 x ArH), 8.10, 8.33, 8.68 and 8.86 (each 1H, d, J-8.0 Hz, ArH), 9.80, 10.11 and 11.57 (each 1H, br, NH) ◊ Analysis (C26H26N405 · HC1. 1 3/4 H20) C, Η (N) (methyl-5 ^ dimethylaminoethylammonium amino-AHMA-carbamic acid ethyl ester (34) is from (16) (310 mg, 0-75 mmol) and ethyl formate (106 Mg 1 0.98 millimolar) Synthesis: yield 105 g (30%); melting point 24 &amp; -3 ° C; NMR (DMSO-d6) &lt; 5 1.21 (3H, t, J = 7.0 Hz, Me), 2 · 74 (3H, s, Me), 2.86 (6H's, NMe2), 3_46 and 3.82 (each 2H, brs, 2 x CH2), 4.09 (2H, q 'J = 7.0 Hz, CH2), 4.44 (2H, s, CH2), 5.20 (1H, br, OH), 6.97 (1H, s, ArH), 7.38 II ViM '-UK SLS B 033-ISUP DOC • 13- 4 ^ 422 5 $ (1H, t' J = 8.0 Hz, ArH), 7.42 and 7.48 (1H, s, 2 x ArH each), 7.58 (1H, t, J = 8.0 Hz, ArH), 7.94, 8.24, 8.59 and 8.93 (1H each, d, J = 8.0 Hz, ArH), 9.93, 10.02 and 10.82 (1H each, brs, 3 x NH). (C29H33N504 · HO 5 H20) C, H, N. I. Γ "， ί ViiKM.S I3.4: 93i-ISUP DOC -14- Pharmacological test: Table 3: In vitro cytotoxic compounds that inhibit the growth of human leukemia HL-60 cells IC5G (eM) that inhibits human leukemia HL-60 ) Compound inhibits IC50OC // M of human leukemia HL-60) AHMA 0.027 18 0.0044 5 0.011 23 0.010 6 0.0076 24 0.0047 7 0.29 25 0.088 8 0.13 26 0.0057 9 14.0 27 3.8- 10 0.15 28 0.031 11 0.37 29 0.067 12 1.5 30 0.13 13 0.12 31 0.032 14 0.038 32 0.0097 15 0.093 33 0.011 16 0.0074 34 0.0023: !! Wi k SI SH 4: &lt;? 3 &gt; ISUP DOC * 15-Table 4: Inhibition of growth of human leukemia HL-60 cells In vitro cytotoxicity

__AHMA 17 18 19 20 4 21 22 R1 Methyl ethyl n-propyl isobutyl third butyl c6H5 CH2e6H5 Inhibits HL-60 Qob M) 0.027 0.0085 0.0044 0.0080 0.0090 0.024 0,161 0,029 Table 5: Compound (18) pairs B6D2F! Mice loaded with Sarcoma 180 and Lewis lung cancer ..., the anti-cancer activity varies by the average weight (g) Mean tumor body fines (regulated by reason, tumor cell dose (mg / kg) Day 7 Day 10 Day 14 Day 7 Day 10 Day 14 barcoma 180 Control group -0.5 +0.7 +1.0 1.00 1.00 1.00 3.0 -2.0 -0.7 -0.8 1.24 1.21 0.74 5.0 -2.6 + 1.0 + 1.2 0.06 0.63 0.80 7.0 -3.4 -0.1 -0.4 0.22 &lt; 0.01 &lt; 0.01 Lewis lung cancer control group -1.0 -0.1 +0.5 1.00 1.00 1.00 3.0 -2.3 -Γ.3 -0.8 0.80 0.63 0.68 6.0 -3.0 -2.6 -0.5 0.44 0.37 0.52 ί Γ \ WOC SLS ΒV42W5,1SLP DOC -16-

43422S Table 6: Therapeutic effect of AHMA, compound (18) and compound (4) on B6D2F | Mice carrying P 388 leukemia Drug dose (mg / kg) and procedure, V Average weight change on day 1 (g) Day 7 Day 9 Day 11 Mean survival time (Sky SD) Life expectancy increase (%) Toxic death control group 0 21.8 0 0/5 3 16 (Q2Dx5) +0.8 -0.5 -2.1 i4.9 soil L1 133 0/5 22 (Q2Dx5) 23.8 -1.3 -1.5 -2.8 21,1 ± 2.2 230 0/5 30 (Q2Dx5) 22.6 +0.2 -0.1 -0.2 21.8 ± 4.0 240 0/4 18! 0 (Q2Dx5) 22.9 -0.2 -0.4 -0.1 18.4 ± 1.2 [SS 0/5 15 (Q2Dx5) 23.0 -1: 6 -2.0 -3.7 13.2 ^ 4.2 106 4/5 4 12 (Q2Dx5) 23.1 -0.10 -0.7 +0.3 1S.0 ± 1.3 181 0/5 t8 (Q2Dx5) 23.9 -1-.3 -1-2 -1.6 22.1 = 2.0 '245 0/5 24 (Q2Dx5) 22.3 -1.4 -1.4 -1.8 21.0 two 4.0 22S 2/4 II \ ί': 'ΛΓΚ SI S β 4; 0 ^ -Ι5υΡ DOC -17-

Claims (1)

4342 ^ ^ ____. No. 8 5 1 02 8 8 7 篆 Please file &gt; 'Chinese patent application scope _ Zhu Benhe: year 5 ^) A8 BS C8 D8 S9. 5. year .X. Patent application scope ( I) Compound (I) (Please read the precautions on the back before filling out this page) The Central Government Bureau of the Ministry of Economic Affairs has printed an alkyl group among them; or '' phenyl; 'R2 is hydrogen; , Where mCrCe alkyl or —phenyl; or acetoxane carbonyl with —CO (CH2) nCOCH3, where n = 丨 -3; and R3 and R4 are substituents at different positions on the acridine ring (ie C-2 '-C-7'), and R3 and R4 may be the same or different, and individually represent: hydrogen; C "C6 alkyl; Ci-CV ^ oxygen; nitro: amine alkylamine of the formula -NH (CH2) nNRdRe Groups, where 1 ^ and Re may be the same or different, and each represents hydrogen, and C | -C6 is a borrowed group of the formula-(CH2) nOH, where n = 1 to 3, or CVC6 haloalkyl; -C〇NHRf alkylamine carbonyl group, in which R ^ CVCfi alkyl group; this paper scale is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) A8 B8 C8 D8 43422® Six, patent application scope -CONH (CH2 ) nNRgRht alkylamine alkylamine carbonyl group, wherein n = 1. 5 and 1 ^ and Rh may be the same or different, each represents hydrogen or crC6 alkyl; halogen group: a carbamate group of the formula -CH ^ CONHRf, Where "as defined previously Burned milk methyl group with formula -CH2OCORf, where Rf is as previously defined; alkyl sulfonate group with formula -S03Rf, where Rf is as previously defined; Burning group with formula -SOjR / 'Wherein Rf is as defined above; the prerequisite is that when R2, R3 and R4 are argon, Ri is not a -third butyl; and a pharmaceutically acceptable salt thereof. 2. The compound according to item 丨 of the scope of patent application, which is selected from the group consisting of: N-[3-(acridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate: N-[3 -(Acridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenylamine Formamidine n-propyl m: N · [3-(acridin-9-yl) amino-5 vhydroxymethyl] benzyl carbamic acid isopropyl ester: N-[3-(acridin-9 'yl) amine N-Butyl-5 -hydroxymethyl] phenylcarbamate; N-[3-(acridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate benzene-2-Applicable to this paper China National Standards &lt; CNS) A4 Specification (210X297mm) (Please read the note on the back before filling out this page &gt; Order ABCD printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 6. Application for Patent Scope Ester: N- [3- (3-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (3-methylacridin-9-yl) Amino-5-hydroxyfluorenyl] phenylcarbamate; N- [3- (3-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N-[3-(3 -methylacridin-9 -yl) Isopropyl-5-hydroxymethyl] phenylcarbamate; N- [3- (3-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; * N-[3-(3 -methylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamic acid isobutyl ester; N- [3- (3 -methylacridin-9 -Yl) amino-5-hydroxymethyl] phenylcarbamic acid third butyl ester; N-[3-(3-methylacridin-9 -yl) amino-5 -hydroxymethyl] phenylamine Phenyl formate; N- [3- (4-methylacridin-9-yl) amino-5-hydroxymethyl] benzylamine (please read the precautions on the back before filling this page)- The staff of the Central Ministry of Economic Affairs of the People's Republic of China cooperated with Du Du to produce dagger 0 S A§ § N-methylpyridinyl Mlg Λ) · Methyl carbamoyl --- Methyl ¾ D-B B § N Methylpyridyl sulfonium \ ) / Methylaminobenzyl I-Methylbenzidine S Propionate N Methylpyridinylmethylaminobenzylbenzene hydrazine J Methylbenzidine Θ Propionate § The standard of this paper is applicable to Chinese National Standards (CNS) Α4 is present (210 × 297 mm) 43422S Λ8 B8 C8 D8 ί Printed by the Ministry of Foreign Trade and Industry Standards Bureau Employee Consumer Cooperatives Range, 'jN-[3- (4-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-butyl ester; N- [3- (4-methylacridin- 9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isobutyl ester; N- [3- (4-methylacridin-9-yl) amino-5-hydroxymethyl] phenylamine Tert-butyl formate; N- [3- (4-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid phenyl ester; ~ 'N-[3-(3 -nitro Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N-[3-(3-nitroacridin-9-yl) amino-5 -hydroxymethyl] Phenylaminocarbamate; 'N-[3-(3 -Nitroacridin-9 -yl) amino-5 -hydroxymethyl] phenylaminoacetic acid n-propyl ester;-N-[3- (3 -Nitroacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate isopropyl; N-[3-(3 -nitroacridin-9 -yl) amino-5 -Hydroxymethyl] phenylcarbamate n-butyl; N-[3-(3-nitroacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate isobutyl; N-[ 3-(3 -nitroacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamic acid third butyl ester; N-[3-(3 -nitroacridin-9 -yl) amine -5 -hydroxymethyl] Benzyl Carbamate; N-[3-(4 -Nitroacridin-9 -yl) amino-5 -hydroxymethyl] phenylamine methyl-4- This paper ft scale applies to Chinese National Standard (CNS) A4 Regulations (210X297mm) (Please read the notes on the back before filling out this page) 434225 A8 B8 C8 D8 Printed by the Central Standards Bureau of the Ministry of Economic Affairs, shoulder workers' consumer cooperatives 6. Application for patents Methyl acid ester: N- [3 -(4-nitroacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-nitroacridin-9-yl) amino-5 -Hydroxymethyl] phenylamine T-n-propyl acid; N- [3- (4-nitroacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isopropyl ester; N- [3-(4 -Nitroacridin-9 -yl) amino · 5-hydroxy] phenylcarbamate n-butyl; N-[3-(4-nitroacridin-9 -yl) amino- 5 -Hydroxymethyl] benzylcarbamate isobutyl ester; 'N-[3-(4-nitroacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate tert-butyl ester; N-[3-(4-Nitroacridin-9 -yl) amino-5 -hydroxymethyl 1 phenylcarbamate; N-[3-(3-hydroxycarbonylacridin-9 -yl) Amino-5 -hydroxymethyl] phenylcarbamate N-[3-(3-hydroxycarbonylacridin-9-yl) amino-5 -hydroxyfluorenyl] phenylcarbamate; N- [3- (3-hydroxycarbonylacridin-9-yl) Amino-5-hydroxymethyl] phenylcarbamate n-propyl ester; t N-[3-(3-hydroxycarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate isopropyl Ester; + N-[3-(3 -hydroxycarbonylacridin-9 -yl) amino-5 -hydroxyfluorenyl] phenylcarbamic acid n-butyl ester; -5- This paper size applies to China National Standards (CNS &gt; A4 (210x297 mm) (please read the precautions on the back before filling out this page) 43422§ A8 BS C8 D8 The policy of employee consumer cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 6. The scope of patent application N- [3- ( 3-hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid isobutyl ester; N- [3- (3-hydroxycarbonylacridin-9-yl) amino-5 · Hydroxymethyl] phenylcarbamic acid third butyl ester; N- [3- (3-hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminophosphonic acid phenyl ester; N-[ 3-(4-hydroxycarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate; ~ 'N-[3-(4-hydroxycarbonylacridin-9 -yl) amine 5-Hydroxyfluorenyl] phenylcarbamic acid Ester; N-[3-(4-hydroxycarbonylacridin-9. * Yl) amino-5 -hydroxymethyl] n-propylcarbamate; N-[3-(4-hydroxycarbonylacridin -9-yl) amino-5 -hydroxymethyl] phenylaminoisopropyl isopropyl; ^ N-[3-(4-hydroxycarbonylacridin-9 -yl) amino-5 -hydroxymethyl] N-butyl phenylcarbamate; N-[3-(4-hydroxycarbonylacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate isobutyl; N-[3-(4- Hydroxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylaminoacid tert-butyl ester; N-[3-(4-hydroxycarbonylacridin-9 -ylaminoamine 5 -hydroxyl Methyl] phenyl phenyl carbamate; N-[3-(3 methoxycarbonylacridine: 9-蓦) amino-5 -hydroxymethyl] phenyl carbamate; N- [3- (3 -Methoxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenyl-6-(Please read the precautions on the reverse side before filling out this page) This paper uses the Chinese National Standard (CNS) Α4 ^ Grid (210X297mm) 43422S ^ Industrial Consumer Cooperatives of the Central Standards Bureau of the Ministry of Foreign Affairs of the People's Republic of China printed policy A8 B8 C8 D8 ττ, the scope of patent applications for urethane; ) Amino-5-hydroxymethyl ] Phenylcarbamate n-propyl ester; N- [3- (3-methoxycarbonylacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate isopropyl ester; N-[3-( 3 -methoxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-butyl ester: N-[3-(3 -methoxycarbonylacridin-9 -yl) amino- 5'hydroxymethyl] phenylcarbamate isobutyl ester; Ν-[3-(3-methoxycarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate tert-butyl ester; -_ 'Ν-[3-(3 -methoxycarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamic acid phenyl ester; Ν-[3-(4 -fluorenoxycarbonylacridine -9-yl) amino-5 -hydroxy'methyl] phenylcarbamate; Ν-[3-(4-methoxycarbonylacridin-9 -yl) amino-5 -hydroxymethyl] benzene N- [3-(4-methoxycarbonylacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamic acid n-propyl ester; N-[3-(4- Methoxycarbonylacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate isopropyl; ^ N-[3-(4 -methoxycarbonylacridin-9 -yl) amino · 5 -Hydroxymethyl] phenyl carbamate;. Ν-[3-(4-methoxycarbonylacridin-9-yl ) Amino-5 -hydroxymethyl] phenylcarbamic acid isobutyl ester; (Please read the precautions on the back before filling this page) This paper has a standard size of Chinese National Standard (CNS) A4 (210 × 297 cm) 434225 A8 &amp; S C8 D8 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 6. Application for patents N- [3- (4-methoxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenyl Tert-butyl carbamate; N- [3- (4-methoxycarbonylacridin-9-yl) amino-5-hydroxymethyl] phenyl carbamate; N- [3- (3-amine Carbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N-[3-(3-aminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] Phenylcarbamate; "* N-[3-(3-aminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate n-propyl; N-[3-(3 -Aminocarbonylacridine-9% yl) amino-5 -hydroxymethylJ phenylcarbamate isopropyl; N- [3- (3-aminocarbonylacridin-9-yl) amino-5-hydroxy Methyl] n-butylbenzylcarbamate; — N-[3-(3-aminocarbonylacridin-9 -yl) amino-5 -hydroxyfluorenyl] phenylcarbamate isobutyl; N-[3 -(3-aminocarbonyl Pyridin-9-yl) amino · 5-hydroxymethyl] phenylcarbamic acid tert-butyl ester; N-[3-(3-aminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] Phenyl phenyl carbamate; N-[3-(4-aminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] benzylcarbamate; N-[3-(4-aminocarbonyl Acridine-9-yl) -amino-5 -hydroxymethyl] benzyl urethane; N-[3-(4-aminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] Phenylamine-8- (Please read the precautions on the back before filling this page) Chinese Standard (CNS) Α4 ^ (210X297 mm) for this paper 43422® AS B8 C8 D8 Bureau of the Consumer Cooperatives of India 6. Application for patents n-propyl formate; N- [3- (4-aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate isopropyl; N -[3- (4-aminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid n-butyl ester; N- [3- (4-aminocarbonylacridin-9-yl) Amino-5-hydroxymethyl] phenylcarbamic acid isobutyl ester; N- [3- (4-aminocarbonylacridin-9-yl) amino-5-5-methyl] phenylcarbamic acid tert-butyl Esters; N-[3-(4-aminocarbonyl acryl -9-yl) amino-5 -hydroxymethyl] phenylcarbamate; 'N-[3-(3-methylaminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] benzene Methylcarbamate; N-[3-(3-methylaminocarbonylacridin-9 -yl) amino-5 -hydroxy'methyl] phenylcarbamate; N-[3-(3 -methyl Aminocarbonylacridin-9-yl) amino-5 -hydroxymethyl] phenylaminoacetic acid n-propyl ester; N-[3-(3-methylaminocarbonylacridin-9 -yl) amino-5- Isopropyl methylol] phenylcarbamate; N-[3-(3-methylaminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate; n- [3-(3 -Methylaminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamic acid isobutyl ester;. N- [3- (3-Amineaminocarbonylacridine-9- Amino) amino-5-hydroxymethyl] phenyl carbamate tert-butyl ester; -9- (Please read the notes on the back before filling in this page) The paper scale is quick to make Chinese painters accurate (CNS) Α4 Specification (2) 0 × 297 mm Α8 Β8 C8 D8 Employee Consumer Cooperative Cooperative of the Central Standards Bureau of the Ministry of Economic Affairs of the People's Republic of China 6. Application for patents N- [3- (3-methylaminocarbonylacridin-9-yl) amino-5- Hydroxymethyl] phenylamine Phenyl ester; N- [3- (4-methylaminocarbonylacridine-9-yl) amino-5-hydroxymethyl] benzylcarbamate; N-[3-(4-methylaminecarbonylacridine -9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-methylaminocarbonylacridin-9-yl) amino-5-hydroxymethyl] phenyl N-propyl carbamate; ~ 'N · [3-(4-methylaminecarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate isopropyl; N- [3- (4 -Methylaminocarbonylacridine ~ 9-yl) amino-5-hydroxymethyl] phenylcarbamic acid n-butyl ester; N- [3- (4-methylaminocarbonylacridin-9-yl) amino-5 -Hydroxymethyl] phenylcarbamate isobutyl ester; 'N-[3-(4-methylaminecarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate tert-butyl ester ; N-[3-(4 -methylaminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamic acid phenyl ester; \. N-[3-(3-N, N -Di Methylaminocarbonylacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate; N-[3-(3-N, N -dimethylaminecarbonyl ^ pyridin-9 -yl) Amino 5-hydroxymethyl] benzyl urethane; N-[3-(3 · N, N -dimethylaminocarbonylacridin-9 -yl) amino-5- Hydroxymethyl] n-propyl phenylcarbamate; N-[3-(3-N, N -dimethylaminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl-10- (Please read the back first Note: Please fill in this page again.) This paper's standard is applicable to Chinese National Standards (CNS). Α4 grid (210 × 297 mm) Α8 Ββ C8 D8 Q3 &quot; Printed by the Central Consumer Bureau of Staff Consumer Cooperatives 6. Scope of patent application] Benzene Isopropylaminocarbamate; N- [3- (3-N, N-dimethylaminecarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid n-butyl ester; N- [ 3- (3-N, N-dimethylaminecarbonylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate isobutyl ester; N- [3- (3-N, N -di Sulfonylaminocarbonylacridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamic acid tert-butyl ester; N-[3-(3-N, N -dimethylaminocarbonylacridin-9 -yl , Phenylamino-5 -hydroxymethyl] phenylcarbamate; N-[3-(4-N, N -dimethylaminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] benzene Methyl carbamate;… 'N-[3-(4-N, N dimethylaminocarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenylaminoacetic acid ethyl ester; N- [3-(4-N, N-dimethylamine carbonyl acryl Pyridin-9-yl) amine-yl-5 -hydroxymethyl] phenylaminophosphonium n-propyl ester; N-[3-(4-N, N -diamidoaminocarbonylacridin-9 -yl) amino -5 · Hydroxymethyl] phenyl isopropylcarbamate; N-[3-(4-N, N -dimethylaminecarbonylacridin-9 -yl) amino-5 -hydroxymethyl] benzylamine N-butyl formate; N-[3-(4-N, N -dimethylaminocarbonylacridine 9 -yl) amino-5 -hydroxymethyl] isopropyl butylcarbamate; ^ N-[3 -(4 · N, N · Diamidocarbonylacridin-9 · yl) amino-5 -hydroxymethyl J tertyl carbamic acid third butyl ester;. N-[3-(4-N, N- Dimethylaminocarbonylacridin-9-yl) amino-5 -hydroxymethyl] benzyl carbamic acid benzene; -11-(Please read the precautions on the back before filling this page) This paper is suitable for β Chinese National Standards (CNS &gt; M now (210X297 cm) A8 BS C8 D8: ^ Printed by the staff of the Central Standards Bureau of the Ministry of Foreign Affairs of the People's Republic of China, F Cooperatives 6. Application scope, N-[3-(3 -methoxy Acridine-9-yl) amino-5 -methylol] methyl benzyl aminocarbamate; N- [3- (3- (oxoacridin-9-yl) amino-5-hydroxymethyl] Phenyl urethane; N- [3- (3- -methoxy Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-propyl; N- [3- (3- (methoxyacridin-9-yl) amino-5-hydroxymethyl ] Phenylaminophosphonate isopropyl ester; _ 'N- [3- (3-methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid n-butyl ester; N-[ 3-(3-methoxyacridinyl-amino) amino-5 -hydroxymethyl J isopropyl carbamic acid isobutyl ester; N- [3- (3-methoxyacridin-9-yl) amino -5-hydroxyamidino] phenylcarbamate tert-butyl ester; 'N-[3-(3-methoxyacridin-9yl) amino · 5-hydroxymethyl] phenylcarbamate phenyl ester; N- [3- (4-methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N-[3-(4 -methoxyacridin-9- Ethyl) amino-5 -hydroxymethyl] phenylcarbamate; N · [3-(4-methoxyacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate Propyl ester; N-[3-(4 -methoxyacridin-9 -yl) -amino-5 -hydroxymethyl] phenylcarbamic acid isopropyl ester; N 3-(4 -methoxyacridine -9 -Amino) amino-5 -hydroxymethyl] phenylamine-12- (Please read the precautions on the back before filling this page) The paper scale is applicable to Chinese national standards Quasi (CNS) (210X297 mm) 43422S 8 8 8 8 ABCD Six 'patent pending N-butyl formate; jN- [3- (4-methoxyacridin-9-yl) amino-5 -Hydroxymethyl] phenylcarbamate isobutyl ester; N- [3- (4-methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate tert-butyl ester; N -[3- (4-Methoxyacridin-9-yl) amino-5-hydroxymethyl] benzyl aminosulfonic acid phenyl ester; N-[3-(3 · chloroacridin-9 -yl) Amino-5 -hydroxymethylmethyl] phenylaminocarbamate methyl ester: N-[3-(3 -Acridine-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate 'N-[3-(3 -Acridine-9 -yl) amino-5 -hydroxymethyl] phenylcarbamic acid n-propyl ester; N-[3-(3 -chloroacridin-9 -yl) Amino-5 -hydroxymethyl] phenylaminoacetic acid isopropyl ester; N-[3-(3 -chloroacridin-9 -yl) amino-5 -hydroxymethyl] phenylaminoacetic acid n-butyl Ester; N-[3-(3 -chloroacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamic acid (please read the precautions on the back before filling this page) Bureau ’s Consumer Cooperative Co., Ltd. printed D-N-Naa isodibenzyl ester [3 Dagger 6 3 i_- Dagger 3 NS methyl Amine \ 1 / yl I 9 Pyridinyl chlorochloride *] g Benzyl--Methyl Benzyl &quot; Chloride * 3 / IV Methylanyl -9-methylpyridinyl methanylbenzene ---- Methyl hydroxyamine Base 9 pyridyl chloride I 4 acid methylamino phenyl Benzene 经 3 'Paper size applicable to Chinese National Standard (CNS) A4 specifications (210X297 mm):-Printed by A8 of the Ministry of Economic Affairs of the Central Standardization Bureau of the Ministry of Finance BS C8 D8 ~, scope of patent application, N-[3-(4-Gacridine-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate; N- [3- (4- -Ga Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate n-propyl ester; N- [3- (4- (Acridine-9-yl) amino-5-hydroxymethyl] benzene Isopropylamine amino acid; N-[3-(4-chloroacridin-9 -yl) amino-5 -hydroxymethyl] phenyl n-butylamino acid;-N-[3-(4 -Acridine-9-yl) amino-5 -hydroxymethyl] phenylcarbamate isobutyl; N-[3-(4 -chloroacridin-9 -yl) &gt; amino-5 -hydroxymethyl Phenyl] phenylcarbamate tert-butyl ester; N-[3-(4 -Acridine-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate phenyl ester: _ N-[3-( 4-aminocarbonyl-5 -methyl Acridine-9-yl) amino-5 -hydroxymethyl] phenylcarbamate; N-[3-(4-aminocarbonyl-5 -methylacridin-9 -yl) amino-5- Hydroxymethyl] phenylcarbamate; N-[3-(4 -aminocarbonyl 0-fluorenylacridin-9 -yl) amino-5 -hydroxymethyl] n-propylbenzylcarbamate: N -[3-(4-Aminocarbonyl-5 -methylacryl 4-9 -yl) amino-5 -hydroxymethyl] isopropyl phenylcarbamate; N-[3-(4-aminocarbonyl. 5-methylacryl &lt; -9-yl) amino-5-hydroxymethyl] n-butylbenzylcarbamate; N-[3-(4-aminocarbonyl-5 -methylacridin-9 -yl ） Amine-5 -Hydroxymethyl] -14- (Please read the precautions on the reverse side before filling out this page) This paper is a fast-moving Chinese national standard (CNS) A4 specification (210X 297 mm) ABCD \ ^ · &quot; Printed by the Consumer Affairs Cooperative of the Central Government Bureau 6. Application scope of patents Isobutyl isopropylamine; N-[3-(4 · Aminocarbonyl-5 -methylacridin-9 -yl) amino- Tert-butyl 5-hydroxymethyl] phenylcarbamate; N-[3- (4-aminocarbonyl-5 -fluorenylacridin-9 · yl) amino-5 -hydroxymethyl] phenylcarbamate Phenyl ester; N- [3- (4-Amineaminocarbonyl-5-methylacridin-9-yl) amino-5-hydroxymethyl] benzylcarbamate; N-[3-(4- Methylaminocarbonyl-5 -methylacridine-9 -yl, amine 5 -methylmethyl] phenylcarbamate; N-[3-(4 -methylaminocarbonyl-5 -methylacridine-9 -Yl) amino-5 -hydroxymethyl] phenylcarbamate n-propyl;-'N-[3-(4-methylaminocarbonyl-5 -methylacridin-9 -yl) amino-5- Hydroxymethyl] phenyl isopropyl carbamate; N-[3-( 4-Methylaminocarbonyl-5 -methylacridin-9-yl) amine · methyl-5 · hydroxymethyl] phenylcarbamate n-butyl ester; N-[3-(4-methylaminecarbonyl-5 -methyl Acryl-9-yl) amino-5 -hydroxymethyl] phenylcarbamic acid isobutyl ester: N-[3-(4 -fluorenylaminocarbonyl-5 -methylacridin-9 -yl) amino -5 -Hydroxymethyl] phenylcarbamic acid tert-butyl ester; N-[3-(4-methylaminocarbonyl-5 -methylacridin-9 -yl) amino-5 -hydroxymethyl] phenyl Phenyl carbamate; &amp; N-[3-(4-N, N-dimethylamine carbonyl 0-methylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate; N-[3-(4-N, N -Diamidoaminocarbonyl-5 -methylacridin-9 -yl) amino-5 -hydroxymethyl] phenylaminoacetic acid ethyl ester; -15- ( Please read the notes on the back before filling in this page.) The paper and paper scales are applicable to Chinese National Standards (CNS). · N, N -Diamidocarbonyl-5 -methylacridin-9 -yl) amino-5 -hydroxymethyl] n-propylcarbamate; N-[3-(4-N, N- Dimethylaminocarbonyl-5 -methylacridin-9 -yl) amino-5 -hydroxymethyl] benzene Isopropyl carbamate; N- [3- (4-N, N-dimethylaminecarbonyl-5 -methylacridin-9-yl) amino · 5-hydroxymethyl] phenylaminoacetic acid n-butyl Esters; N- [3- (4-N, N-dimethylaminocarbonyl-5-methylacridin-9-yl) amino-5 -hydroxymethyl] phenyl isoformate; ~ &quot; N- [3- (4-N, N-dimethylaminocarbonyl-5 methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamic acid third butyl ester; N- [3- (4-N, N-Dimethylamine-derived 5-methylacridin-9-yl) amino-5-hydroxymethyl] phenylamine sulfonate; 'N- [3- (4- Aminocarbonyl-5 -methoxyacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N-[3-(4-aminocarbonyl-5 -methoxyacridin- 9-yl) amino-5 -hydroxymethyl] phenylcarbamate; N-[3-(4-aminocarbonyl-5 -methoxyacridine, 9 -yl) amino-5 -hydroxymethyl N-propylphenyl phenylcarbamate; N-[3-(4-aminocarbonyl-5 -methoxyacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate isopropyl; N- [3- (4-aminocarbonyl-5-methoxyI acridine-9-yl) amino-5 -hydroxymethyl] benzyl carbamic acid n-butyl ester; N-[3-(4-aminocarbonyl -5 _methoxyacridin-9-yl) amino-5- Hydroxymethyl] isopropyl butylcarbamate; N-[3-(4-aminocarbonyl-5 -methoxyacridin-9 -yl) amino-5 -hydroxymethyl-16- {Please read the back first Please fill in this page for the matters needing attention) The size of the bound paper is applicable to China National Standard Vehicle (CNS) A4 specification (2 丨 0X297 mm) 43422S H C8 D8 i. Patented scope] phenylcarbamic acid third butyl ester;) N-[3-(4-aminocarbonyl-5 -methoxyacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamic acid Phenyl ester; N- [3- (4-methylaminocarbonyl-5-methoxyacridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamate; N- [3- (4 · Methylaminocarbonyl-5 -methoxyacridin-9 -yl) amino-5 · hydroxymethyl] phenylcarbamate; N- [3-(4-methylaminocarbonyl-5-methoxy Acridine-9-yl) amino-5 -hydroxymethyl] phenylcarbamate n-propyl; N-[3-(4-methylaminecarbonyl-5 -methoxyacridin-9 -yl) amine Isopropyl-5 -hydroxymethyl] phenylcarbamate; -_ 'N-[3- (4-methylaminecarbonyl-5 -methoxyacridin-9-yl) amino-5, hydroxymethyl N-butylphenylphenyl carbamate; Ν-[3-( 4-methylaminocarbonyl-5 -methoxyacridin-9-yl) amino 5-hydroxymethyl] phenylcarbamic acid isobutyl ester; Ν-[3-(4-methylaminecarbonyl-5 -methoxy Acridine-9yl) amino-5 -hydroxymethyl] phenylaminoacid tert-butyl ester; Ν-[3-(4-methylaminocarbonyl-5 · methoxyacridin-9 -yl) Amino-5 -hydroxymethyl] phenylcarbamate; N- [3- (4-N, N -dimethylaminocarbonyl-5 -methoxyacridin-9 -yl) amino, 5- Hydroxymethyl] phenylcarbamate; Ν-[3-(4-Ν, Ν -dimethylaminocarbonyl-5 -methoxyacridin-9 -yl) amino-5 -hydroxymethyl] benzene Ethyl carbamate; Ν-[3 (4-Ν, Ν -dimethylaminocarbonyl-5 -methoxyacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate -17- (Please read the precautions on the back before filling this page) The dimensions of this paper are applicable to the Chinese National Standard (CNS) Yatsushiro (210X297 mm) A8 BS C8 D8 &amp; Patent Application Scope (Please read first Note on the back, please fill out this page again} N_ [3- (4-N, N-Dimethylaminecarbonyl-5-methoxyacridin-9-yl) amino-5-5-methylmethyl] benzylamine Isopropyl formate; Ν · [3- (4-N, Ν-dimethylaminocarbonyl-5-methoxymethoxyacridin-9-yl) amino · 5-hydroxymethyl] phenylcarbamate n-butyl; ν · [3- (4-N, N-dimethyl Aminocarbonyl-5-methoxyacridin-9-yl) amino · 5-hydroxymethyl] phenylcarbamic acid isobutyl ester; Ν · [3- (4-N, N -dimethylaminocarbonyl-5) _Methoxyacridin_9 · yl) amino-5 -hydroxymethyl] phenylcarbamic acid third butyl ester; ~ ν_ [3- (4-N, N -dimethylaminocarbonyl-5 -fluorenyloxy) Acryl-9-yl) amino-5 -hydroxymethyl] benzylcarbamate; N- [3- (acridin-9-yl) amino ~ 5 -ethoxymethyl] benzyl Methyl carbamate; Ν- [3- (acridin-9-yl) amino-5-acetamidoxymethyl] phenylhexyl carbamate;-Ν- [3- (叶叶 -9 -yl) Amino-5-ethyl alcohol oxymethyl] benzyl carbamic acid n-propyl g purpose; far-9-yl) amino-5-acetamido oxymethyl] phenylcarbamic acid isopropyl ester; • Central Bureau of Standards N- [3-(acridin-9-yl) amino-5-aminoacetoxymethyl] benzylcarbamate printed by employee consumer cooperatives; N- [3- (acridin-9-yl) Aminoacetamidooxymethyl] benzylcarbamic acid isobutyl ester; N- [3- (m9-yl) amino group K-oxymethyl] leather aminocarbamic acid Butyl ester; N- [3- (acridin-9-yl) amino-5-ethoxymethyl t, 1] benzylamidoic acid-18- Not applicable to Chinese National Standards (CNS) Α4 grid on paper (2 〖〇χ2ί! 7mm） 4342g printed by the Consumer Standards Cooperative of the Central Bureau of Standards 88 88 C8 D8 6. Application scope of patents Phenyl esters; N- [3- (acridin-9-yl) amino] -5- Acetyloxymethyl] phenylcarbamate; N-[3-(acridin-9 -yl) amino] -5 -ethoxybenzyl.ethyl] phenylaminoacetate; N- [ 3- (4-methylaminocarbonylacridin-9-yl) amino-5-methylacetoxymethyl] phenylcarbamate; N-[3-(4 -methylaminocarbonylacridin-9 -yl ) Amino-5 -ethoxymethyl] phenylcarbamate; N-[3-(4-methylaminecarbonyl 5 -methylacridin-9 -yl) amino-5 -acetoxymethyl Methyl] phenylcarbamate; -_ 'N- [3- (4-methylaminecarbonyl-5 -methylacridin · 9-yl) amino-5 -ethoxymethyl] phenylamine Ethyl Ester; N-[3-(4-methylaminocarbonyl-5 -methoxyacridin-9 -yl) amino-5 methylacetoxymethyl] phenylcarbamate; N-[3- (4-methylaminocarbonyl-5-methoxyacridin-9-yl) amino-5-acetamidine Methyl] phenylcarbamate; N-[3-(4-methylaminecarbonyl-6 -nitroacridin-9 -yl) amino-5 -hydroxymethyl] benzylcarbamate; N- [3-(4-methylaminocarbonyl-6 -nitroacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate; &amp; Μ-[3-(4-methylaminecarbonyl -7-nitroacridin-9-yl) amino-5 -hydroxymethylj-benzylcarbamate;. N-[3-(4 fluorenylaminocarbonyl · 7 -nitroacridin-9 -yl ） Amino-5 -hydroxymethyl] phenylcarbamate; -19- (Please read the notes on the back before filling out this page) 'va This paper is suitable for 5 national standards (CNS) A4 Specifications (210X297 mm) 8888 ABCD Procurement Department Central Standards Bureau Employees Consumer Cooperatives Cooperative Seal 6. Application for Patent νN- [3- (4 · methylaminecarbonyl-6-methylaminoacridin-9-yl) amine Methyl-5 · hydroxymethyl] phenylcarbamate; N- [3- (4-methylaminocarbonyl-6-methylaminoacridin-9-yl) amino-5-hydroxymethyl] benzyl Ethyl carbamate; N- [3- (4-methylaminocarbonyl-7-methylaminoacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-methylaminocarbonyl-7-methylaminoacridine-9 -Yl) amino-5-amidomethyl] phenylcarbamate; N-[3-(3,6-dinitroacridin-9 -yl) amino-5 -hydroxymethyl] phenyl Methyl carbamate; N-[3-(3,6-dinitroacridin ~ 9 -yl) amino-5 -hydroxymethyl] phenylcarbamate: N-[3-(4,5 -Dinitroacridine 9-yl) amino-5 -hydroxymethyl] phenylcarbamate; 'N- [3- (4,5-dinitroacridin-9-yl) amino Ethyl-5-hydroxymethyl] phenylaminophosphonate; N-{3-[3,6-bis (dimethylaminoethylamino) acridin-9 -yl] amino-5-hydroxymethyl } Methylbenzylcarbamate; N-{3-[3,6-bis (dimethylaminoethylamino) acridin-9-yl] amino · 5-hydroxymethyl} phenylcarbamate ; N-{3-[4,5-bis (dimethylaminoethylamino) acridin-9 · yl] amino-5 · hydroxymethyl} benzylcarbamate: and N- {3- [4,5 · bis (dimethylaminoethylidene) acridin-9-yl] amino-5-hydroxymethyl} phenylcarbamate. 3. The compound according to item 2 of the scope of patent application, which is selected from the following: -20- This paper size is applicable to China National Sample Rate (CNS) A4 specification (210X297 cm) --------- V-- (Please read the notes on the back before filling out this page) Ordering ^ Yes, the Central Standards Bureau Employees Consumer Cooperative Press 4342 ^ 3 a8 B8 C8 D8 VI. Patent Application Scope N-[3-(acridin-9 -based) Amino-5 · methylol] phenylcarbamate; N-[3-(acridin-9 -yl) amino-5 -hydroxymethyl] benzylaminocarbamate; N-[3 -(Acridin-9-yl) amino-5-hydroxyfluorenyl] phenylcarbamate n-propyl; N- [3- (acridin-9-yl) amino-5-hydroxymethyl] phenyl Phenyl carbamate; — N-[3-(4-methylacridin-9 -yl) amino-5 -hydroxymethyl] phenylcarbamate; N-[3-(4-nitroacryl Pyridin-9-yl) amino-5 -hydroxymethyl] phenyl 'urethane; N-[3-(4-hydroxycarbonylacridin-9 -yl) amino · 5-hydroxymethyl] benzene Ethyl carbamate; _ N-[3-(4-methoxycarbonylacridin-9 -yl) amino-5 -hydroxymethyl] phenyl carbamate; N-[3-(4 -amine Carbonylacridin-9-yl) amino -5 -hydroxymethyl] phenylcarbamate; N-[3-(4-methylaminecarbonylacridin-9 -yl) amino-5 -hydroxymethyl] benzylcarbamate; N- [3-(4-N, N -dimethylaminocarbonyl) amidin-9 -yl) amino-5 -hydroxymethyl] benzylcarbamate; N-[3-(4 -fluorenyloxyacyl Pyridin-9-yl) -amino-5 -hydroxymethyl] phenylcarbamate; N-[3-(3 -aminoacridin-9 -yl) amino-5 -hydroxymethyl] phenyl Urethane-21-This paper ruler / 1 is applicable to China National Standards (CNS) A4 wash (210X297 mm) (诮 Please read the precautions on the back before filling this page) Order 8 8 8 8 ABCD-&quot; Central Printed by the Consumer Cooperatives of the Bureau of Standards. 6. Scope of patent applications. Ethyl esters; N- [3- (4-chloroacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [ 3- (4-methylaminocarbonyl-5-methylacridin-9-yl) amino-5-hydroxymethyl] phenylcarbamate; N- [3- (4-N, N-dimethyl Aminocarbonyl-5 -methylacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate; N-[3-(4-chloroacridin-9 -yl) amino-5 Hydroxymethyl] phenylamine 'ethyl formate: N-[3-(4-methylamine carbonyl -5 -methoxyacridin-9-yl) amino · 5-hydroxymethyl] phenylcarbamate; 'N- [3- (4-N, N -dimethylaminocarbonyl-5-methyl Oxyacridin-9-yl) amino-5 -hydroxymethyl] phenylcarbamate; and N-[3-(3-methylaminocarbonyl-5 -nitroacridin-9 -yl) amine -Yl-5 -hydroxymethyl] phenylcarbamate. 4. The compound according to item 3 of the scope of the patent application, which is N- [3- (. Acridine-9-yl) amino-5-hydroxymethyl] phenylcarbamate. 5. A method of preparing a compound according to item 1 of the scope of the patent application, which comprises: · condensing a mono-, di- or poly-substituted 9-acridine chloride with 3,5-diaminofluorene under appropriate conditions; Alcohol dihydrogenate to form mono-, di-, or poly-substituted 3-(acridin-9-yl) amino-5 -hydroxymethylaniline-22 with formula (II) Standard (CNS) A4 see the standard (210X297 mm) (Please read the precautions on the back before filling in this tile) 4342g§ A8 B8 C8 D8 6. Scope of patent application R3 and R4 are defined by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs as defined in item 1 of the scope of patent application; (b) the compound of formula (11) and a picoformate with formula XCOOt (where X is a halogen, Into a CrC6 alkyl group or a optionally substituted benzyl group) under appropriate conditions to form a compound of formula (I) in which R2 is hydrogen; (c) if necessary, 0-halogenated under appropriate conditions where R2 is hydrogen A compound of formula (ί) to produce a compound of formula (I) in which R2 is a fluorenyl group of formula -CORa (where 1 ^ is Cr C6 alkyl or phenyl); or R2 is a compound of formula -CO (CH2) nCOCH3 Acetane carbonyl (where n = 1 to 3) is a compound of formula (I);! Cl. If necessary, the compound of formula (I) is appropriately converted into a pharmaceutically acceptable salt thereof. 6. —Species (11) Compound-23- This paper is applicable to China National Standards (CNS) A4 ^ i (210X 297 mm) (Please read the notes on the back before filling this page) 022434 ABCD Patent Application Printed by the Consumer Affairs Cooperative of the Central Government Bureau of the Ministry of Economic Affairs, where R3 and R4 are as defined in item 1 of the scope of patent application; the prerequisite is that at least one of R3 and R4 is not hydrogen; and its pharmaceutically acceptable salt. -· 7. The compound according to item 6 of the scope of patent application, which is selected from the group consisting of: '3-(4-methylacridin-9 -yl) amino-5 -hydroxymethylbenzylamine; 3-(4- Nitroacridin-9-yl) amino-5 -hydroxymethylaniline 1 3-(4 -methylaminoacridin-9 -yl) amino-5 -hydroxymethylaniline; 3- (4-N , N-Diamidoaminoacridin-9-yl) amino-5 -hydroxymethylaniline; 3-(4-methoxycarbonylacridin-9-yl) amino-5 -hydroxymethylaniline; 3 -(4-methylaminocarbonylacridin-9-yl) amino-5 hydroxymethylaniline; 3-(4-N, N-dimethylaminocarbonylacridin-9-yl) amino-5 -hydroxymethyl Aniline; i 3-(4 · methoxy acridine-9 -yl) amino 5-hydroxymethylaniline; 3-(4-N, N -dimethylaminocarbonyl-5 -methoxy acridine- 9 -yl) amino-5 -hydroxymethylaniline; 3-(acridin-9 -yl) amino-5 -ethoxymethylaniline; -24- --------- '4 -(Please read the note on the back, and then fill out this page) The size of the paper is applicable to the Chinese National Standard (CNS) A4 (210X 297 mm) 43422S Λ8 B8 C8 D8, the scope of patent application 3- (4 -Methylaminocarbonylacridin-9-yl) amino-5-acetamidine Aniline; 3- (4-methylaminocarbonyl-5-methylacridin-9-yl) amino-5-acetamidomethylaniline; and 3- (4-methylaminecarbonyl-5-methoxyacridine Pyridin-9-yl) amino-5-acetamidoxymethylaniline. 8. A pharmaceutical composition for combating leukemia and tumor cells, which contains an effective amount of a compound of formula (I) as an active ingredient (please read the precautions on the back before filling this page) NHCOOR1 CH ^ OR- R3 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs, where 1 ^ is CPC6 alkyl; or phenyl: R2 is hydrogen: hydrazone with formula -CORa, where phenyl or phenyl: or -CO (CH2) ethanoyl carbonyl of nCOCH3, where n = 1 to 3; and R3 and R4 are substituents at different positions on the acridine ring (ie, C-2'-C-7 '), and R3 and R4 It can be the same or different. Individual representatives: Hydrogen; -25- This paper scale is applicable to the national standard (CNS) A4 wash (210X297 mm) Mandatory 3423 A8 B8 ce D8 Printed by the Consumer Cooperatives of the Central Standards Bureau of the Ministry of Economic Affairs 、 Applicable patent scope C 1 C 6 alkyl, Cj-Ca alkyl, nitro: amine alkylamino group of formula -NH (CH2) nNRdRe, where "and Re can be the same or different, and each represents hydrogen, CrC6 alkyl A hydroxyalkyl group of the formula-(CH2) nOH, where n = 1 to 3, or CrC6 ^ alkyl; an alkylamine carbonyl group of -CONHRf, where Rf is a CVC6 alkyl group; a formula of -CONH (CH2) nNRgRh Alkylamine alkylamine group, in which -ny · 5, and Rg and Rh may be the same or different, each represents hydrogen or CrC ^ group; halogen group:--a urethane group of the formula -CH2CONHRf, which y is as defined previously; formula -CH ^ OCORk fe talks about oxymethyl, where rJ &quot; is as defined previously; formula-SO; jRf's performance Ss_burning vinegar group 'where R * &quot; is as previously defined; Formula-S〇2Rf 的 境 横横 基 'where Rf is as defined above; and its pharmaceutically acceptable salt: and its pharmacologically acceptable carrier. 9. A pharmaceutical composition for the fight against leukemia and tumor cells, which Contains an effective amount of the compound of formula (11) for living J-26- This paper is a standard Chinese standard (CNS) A4C (210X297 mm) ^^ 1 m HI I a— bu m j_ —-i if -a (please read the note on the back before filling this page) A8 B3 C8 D8 Patent application scope Among them, R3 and R4 are as defined in item 1 of the scope of patent application. The prerequisite is that at least one of R3 and R4 is not hydrogen; and a pharmaceutically acceptable salt thereof;-and a pharmacologically acceptable carrier thereof. (Please read the precautions on the reverse side before filling out this page) The Central Government Bureau of the Ministry of Economic Affairs and the Ministry of Economic Affairs and Staff Cooperative Cooperative Printing Co., Ltd.-27- The paper scale is applicable to the Chinese National Standard (CNS) A4 (2I0X297 mm) 4342 ^ ^ ____. Article 8 5 1 02 8 8 7 篆 Please file a case> '' Chinese patent application scope _ Zhu Benhe: year 5 ^) A8 BS C8 D8 S9. 5. year. X. patent application scope compound of formula (I) (I) (Please read the precautions on the back before filling out this page) The Central Government Bureau of the Ministry of Economic Affairs has printed an alkyl group among them; or '' phenyl; 'R2 is hydrogen; , Where mCrCe alkyl or —phenyl; or acetoxane carbonyl with —CO (CH2) nCOCH3, where n = 丨 -3; and R3 and R4 are substituents at different positions on the acridine ring (ie C-2 '-C-7'), and R3 and R4 may be the same or different, and individually represent: hydrogen; C "C6 alkyl; Ci-CV ^ oxygen; nitro: amine alkylamine of the formula -NH (CH2) nNRdRe Groups, where 1 ^ and Re may be the same or different, and each represents hydrogen, and C | -C6 is a borrowed group of the formula-(CH2) nOH, where n = 1 to 3, or CVC6 haloalkyl; -COHNHf alkylamine carbonyl group, in which R ^ CVCfi alkyl group; this paper scale is applicable to China National Standard (CNS) A4 specification (210X297 mm) 43422 § Supplementary explanation of Patent Application No. S5102887 in May of that year) Example: A gas-AΗΜΑ hydrochloride (5) 4-methoxymorpholine was added dropwise to the 4-methylmorpholine in an ice bath (2.74 g, 13 mmol) in a suspension of CHCl3 / EtOH (I: 3 v / v). After stirring for 1 hour, the crude 9-chloro-4-methoxyacridine (made from 4-methoxy-9 (10 甲) -acridone, 2.83 g, 13 mmol) was added at 0 °. ) Of CHC13 (15 ml) was added dropwise to the mixture and stirred vigorously for 4 hours. The crude solid product was collected by filtration, washed with EtOH, and then recrystallized from MeOH to give (5): 2.02 g (70%); melting point 247 -8 ° C NMR (DMSO-d6) (5 to .16 (1H, s, OMe), 4.38 and (2H, s, CH2) '5.20 (1H, br, OH), 5.82 (2H, br, NH2), 6.46, 6.51 and 6.64 (1H's' 3 x ArH each), 7.41 (1H, t, J = 8, 7 Hz, ArH), 7.46 (1H, t, J = 8.7 Hz, ArH) , 7.96 (1H, t, J = 8.0 Hz, ArH), 8.27 and 8_37 (1H, d, J = 8.6 Hz, 2 x ArH) '11.33 (1H, brs, NH). Analysis (C2lHl9N302 · 2HC1) C , Η, N. The following compounds were prepared using the same procedure as in synthesis (5): 4'-methylazine-AHMA hydrochloride ⑹ by 4 · fluorenyl-9 (10H) -acridone (1.20 g, 5.70 mmol) Ear) and 4-methylmorpholine (1.21 g '5. ^ 0 mmol): Synthesis: 1.67 g (88%): melting point 264-5 ° C; NMR (〇MSO-d0) &lt; 5 2.78 ( 1H's, Me), 4.37 (2H, s, CH2), 5.18 (1H, br'oH), 5.50 (2H 'br'NH2), 6.39, 6.46, and 6'59 (each 1H, s, 3 x ArH), 7.37 (1H, t 'J = 8.〇Hz' ArH) '1! * H WCK SI.S DOC