CA1251442A - Intermediates for substituted anthra¬1,9-cd|- pyrazol-6(2h)-ones - Google Patents

Abstract

ABSTRACT

Intermediates for preparing substituted anthra-[1,9-cd]pyrazol-6(2H)-ones which have antimicrobial activity, and methods for their preparation. The novel intermediates are: 2-[(hydrazinoethyl)amino]ethanol, prepared by reacting hydrazine with N-(2-hydroxyethyl)aziridine; 5,8-dichloro-1,4,9,10-anthracenetetrone, prepared by oxidizing 5,8-dichloro-1,4-dihydroxy-9,10-anthracenedione; and a compound of general formula:

wherein Z is as defined in the disclosure and claims, prepared by reacting a hydrazine of general formula: H2N-NHZ with a compound of general formula:

Description

- 2 -This is a divisional application of co~ending application, serial no. 432,584, filed July 18, 1983.
BACKGROUND OF THE INVENTION
Several 2,5 and 2,7-disubstituted anthra[l,9 cd]pyrazol 6(2H)-ones are disclosed in the prior literature. See for example J. Chem. Soc., 1630 (1952); J. Chem. ~oc., 189~
(1954). Neither reference discloses any utility for these compounds.

S~MMARY OF THE INVENTION

The invention in its first generic chemical compound aspect is a compound having the structural formula lo w~
X' O ~R~

wherein X, X' and W may be the same or different and are hydrogen, hydroxy, alkoxy having one to four carbon atoms and chlorine; R is H or alkyl of from one to six carbon atoms; Y is H, alkyl of from one to six carbon atoms which may be substituted with an ORl group wherein Rl is H or alkyl of from one to six carbon atoms, or ANR2R3 wherein A
is straight or branched alkylene of from two to eight carbon atoms, R~ and R3 may be the same or different and are H, alkyl of from one to six carbon atoms which may be substituted with OH or an NRaRa wherein Ra may be the same or different and is H or alkyl of from one to three carbon atoms which may be substituted with OH, or NRbRb wherein Rb is the same

3 ~ 2 or different and is H or alkyl of from one to three carbon atoms, or R2 ancl R3 when taken together may be ethylene or may form -(C~2) B

~(C;~2)rn/

wherein n and m may be the same or different and are one, two, or three provided that the sum of n and m is an integer of from three to six, and B is a direct bond, O, S, or N-R4 wherein R4 is H or alkyl of from one to six carbon atoms; R and Y when taken together may be ethylene or may form CLG-l -4-~(C~2)n \
) B
-(CH2)m /
wherein n and m and s are defined above, Z is ~, alk-ll of from one to six carbon atoms ~hich may be substi tuted with an ~(Rl)2, SRl, or ORl group wherein Rl is the same or different and is defined above, or D~IR2R3 wherein D is st~aight or branched al'.Yylene o from t~o to eight carbon atoms which may be sub-stituted with an OH group and R2 and R3 are as defined above; and the pharmaceutically acc~ptable salts thereo~; with the following provisos, 1) when X, ~' and r~7 are R and Z is H, R and Y when taken together do not complete a piperidine ring, ~) when J~ ~ X ~ and r~ are 'I and 2 is CH3, R and Y when taken together do not complete a piperidine ring or a morpholine ring.
The invention sought to be patented in its second generic chemical compound aspect is a compound having the structural Lormula X N N-Z
W-~ ' X' O NRY

w'nerein X; X' and ~ may be the same or different and are H or O~, alkoxy having one to four carbon atoms or chlorine; R is H or alkyl of from one to si:c carbon atoms; Y is H, alkyl of from one to six carbon atoms which may be substituted with an P~l group wherein Rl is ~ or alkyl of from one to six carbon atomsr or A~R2R3 wherein A is straight or hranched aL~ylene of from two to ei~ht carbon atoms, R2 and ~ ~ 5 ~

R3 may be the same or different and are H, al'.~yl of ) Ero~ one to si~ car~on atoms which may ~e substituted with OH or an ~RaRa ~herein Ra may be the same or different and is H or alkyl of from one to three carbon atoms which may be substi~uted with OH, or NRbRb wherein Rb is the same or different and is H
or al~l of from one to three carbon atoms, or R2 and R3 when ta~en together may be ethylene or may form ~(C~2)n\
B

- ~ CEI2 ) in/
wherein n and m may be tne same or different and are one, two, or three provided that the sum of n and m i5 an integer oE from three to six, and B is a direct bond, O, S, or N-R~ wherein R4 is H or alkyl of from one to six carbon atoms; R and Y when taken together may be ethylene or may form (CE~2)n\
B
-~CH2)m /
wherein n, mr and 3 are defined above; Z is H, alkyl oE rom one to six carbon atoms which m~y ~e substituted with an l~(Rl)2, SRl, or OR1 group wherein R1 is the same or different and is defined a~ove, or DNR2R3 wherein D is straight or branched alkylene of from two to eight carbon atoms which may be substituted with an OH group and R2 and R3 are as defined above; and the pharmaceutically accepta~le salts~ thereof; with the following provisos, 1) when X, X', and W are H and Z is H, R and Y when taken together do not co~plete a piperidine ring, 2) when X, X', and W are H and Z is CH3 R and Y when taken together do not complete a piperidine ring or a morpholine ring.

~5~

CL5 1 -5~
The invention sought to be patented in its ! third generic chemical compound aspect is a com~ound ha-~ing the structural Eormula N N-Z
xlx~3, ~i O NRY

wherein X and X' may be the same or different and are ~, OH, alkoxy of one to four carbon atoms or chlorlne;
R is B or alkyl of Lrom one to six carbon atoms; Y is H, alk~l Oe from one to six carbon atoms which may be substi~u~e~ with an ORl group wherein Rl is H or al~yl of from one to six carbon atoms, or ANR2R3 wherein A is al~ylene of from two to 11 carbon atoms, R2 and R3 may be the same or di,ferent and are H, alkyl o from one to six carbon atoms which may be substituted with OH or an NRaRa wherein Ra is H or alk~yl of from one to three carbon atoms which may be substituted with OH, or NRbRb wherein Rb is the same or difrer~nt and is d or alkyl of from one to ~h~ee carbon atoms, or R2 and R3 when t~ken together may be et~ylene or may form ~(C~2)n -(C~2)m~
wnerein n, m, and B are defined above; Z is H, alkyl of from one to six carbon atoms whicn may be substituted with an N~Rl)2, SPl, or ORl sroup wherein Rl is defined above, or DNR2R3 wherein D is al~ylene of from two to 11 carbon atoms which may be substituted with an ~ group and R2 and R3 are as defined above;
and the phar~aceutically acceptable sal.s thereof; with the ~ollowing provisos, 1) when X is H and z is H, R

~25~L~L~l2 and Y when ta'~en together ~o not complete a piperidine ring r 2) ~hen X is H and Z is CH3 R and Y when taken together do not complete a plperidine ring or a morpholine ring.

~~C~2)n\B
-(CH2)m /
wherein n, ~, and B are defined abovei 2 is ~, alkyl of from one t~ six carbon atoms which may be substituted with an N(Rl)2, SRl, or ORl group wherein Rl is defined above, or DNR2R3 wherein D is alkylene of from two to 11 carbon atoms which may be sub~ti~uted with an OH group and R2 and R3 are as defined above;
and the pharmaceutically acceptable salts.thereof; with the followiny provisos, .1) when X i.s H and Z i~ H, R
and Y when taken together do not complete a piperidine ring, 2) when X is H and Z is CH3 R and ~ when ta,cen together do not complete a piperidine ring or a morpholine ring.
The invention in its fourth generic chemical compound aspect is a compound ha~ing the structural formula I
X N - N-z ' O
I
wherein X, and X' may be the same or different and are 'd or OH; R is H or alkyl of from one to si~ carbon atoms; Y is H, alkyl of from one-to 5iX carbon atoms which may be substituted with an ORl group wherein Rl is ~ or alkyl of from one ~o six carbon atoms, or ANR2R3 ~herein A is straight or branched al.~ylene of from two to eight carbon atoms, R2 and R3 may be t`ne J

~;~5~2 same or aifEerent and are ~, alkyl of from one to six car~on âtOmS which may be su~stituted with OH or an NRaRa wherein ~a is the same or dirferent and as H or alkyl o from one to three carbon atoms which may be substituted with OH, or NRbRb wherein Rb is the same or different and is H or alXyl of 'rom one to three carbon atoms, or R2 and R3 when taken together may be ethylene or may form -(C~I2!n\

-(C~12)m/
and m is an integer of from three to si~, and B is a direct ~ond, O, S, or N-R4 wherein R~ is H or alkyl of from one to six carbon atoms; R and Y when taken t:ogether ma~ be ethylene or may Eorm -(CH2)n~
~ B
-(CH2)m~
wherein n, ~, and B are defined above; Z is H, alXyl of from one to six carbon atoms which may be substituted with an N(Xl)2, SRl, or ORl group wherein Rl is the same or different and is as defined above, or DNR2~3 wherein D is straight or branched alX~ylene of Erom two to eight carbon atom3 which may be substituted with an OH group and R2 and R3 are as deined above; and the pharmaceutically acceptable salts thereof; with the following provisos, 1~ ~hen X
and X' are H and Z is H, R, and v when taXen together do not complete a piperidine ring, ~) when X and X' are H and Z is CH3, ~ and Y when taken together do not complete a piperidine ring or a morpholine ring.
The invention in a first subgeneric aspect of its fo~rth chemical co~pound aspec~ is a chemical compound having structural Lormula I wherein X and Xl are O~;
and the pharmaceutically acceptable salts thereo.

~5~

CLG-l -9-The inven~ion in a second subseneric aspect of its fourth chemical compound aspect is a chemical compound na~Jing structural formula I wherein X and X' are H; and the pharmaceutically acceptable salts thereof.
The lnvention in a third subgeneric as~ect of its fourth chemical compound aspect is a chemical compound ha~Jing structural formu~a I wherein A and D are the same or different and are ethylene or propylene; and the pharmaceutically acce~table salts thereof.
The invention in a fourth subgeneric aspect of its fourth chemical compound aspect is a compound having structural formula I' N N-Z' O NR'Y' I' wherein R' is H or alkyl of from 1 to ~ carbon atoms;
Y' is CH2CH~NHCH2CH20H when Z' is alXyl of from one to four c~rbon atoms which may be substituted with an SRi, or o~i group wherein Rl is H or alkyl of from one to four carbon atoms or D'~R2~3 wherein D' is strai~ht or branched alkylene of from t~o to four carbon atoms which may ke substituted with an OH group and P~2 and R3 may be the same or diferent and are H, alkvl of from one to six carbon atoms which may be substituted with an OH or R2 and R3 when taken together may be ethyler.e or may form -(CH~)n' -(C~2)~'/

4L L~ 2 ]~o wherein n' and m' may be the same or different and are one or two provided that the sum of n' and m' :is three or four, and B' is a direct bond, O, ~" or N-R4 wherein R4 is ~ or alkyl of from one to four carbon atoms; or Z' is CH2CH2NHCH2CH2OH when Y' is H, alkyl of from one to six carbon atoms which may be substituted with an ORl group wherein R
is as defined above or A'NR2R3 wherein A' is alkylene of from two to four carbon atoms and R2 and R3 are as defined above; and the pharmaceutically acceptable salts thereof.
The invention in a fifth subgeneric aspect of its fourth chemical compound aspect is a compound having structural formu.a I'' Nl - N-Z"

NR"Y"
I'' wherein R'' is H or alkyl of from one to six carbon atoms;
Y'' is H, alkyl of from one to six carbon atoms which may be substituted with an ORl' group wherein Rl' is H or alkyl of from one to four carbon atoms, or A''NR2'R3' wherein A'' is alkylene of from two to four carbon atoms, R2' and R3' may be the same or different and are H, alkyl of from one to six carbon atoms which may be substituted with an OH or an NRa''Ra'' wherein Ra'' is the same or different and is H or alkyl of from one to three carbon atoms which may be substituted with an OH or R2' and R3' when taken together may be ethylene or may form ~(CH2)n'' -(C~2)m'' ~
wherein n'' and m'' may be the same or different and are one or two provided that the sum of n'' and m'' is three or four, and B'' is a direct bond, O, S, or N-R4lwherein R4' is H *r alkyl of from one to four carbon atoms; Z'' is alkyl of from one to four carbon atoms which may be substituted with an SRi', or ORi' group wherein Ri' is defined above, or D''NR2'R3' wherein D'' is alkylene of from two to four carbon atoms which may be substituted with an OH group and R2' and R3' are as defined above; and the pharmaceutically acceptable salts thereof.
The invention in a sixth subgeneric aspect of its second chemical compound aspect is a compound having the structural formula I' "

OH Nl -N-Z'~

HO' ~
OH O NR"'Y''' I "' wherein R''' is H or alkyl of from one to six carbon atoms;
Y''' is H, alkyl of from one to six carbon atoms which may be substituted with an ORi'' group wherein Ri'' is H or alkyl of from one to four carbon atoms, or A'''NR2''R3'' wherein A''' is alkylene of from two to four carbon atoms, R2'' and R3'' may be the same or different and are H, alkyl of from one to six carbon atoms which may be substituted with an OH or an NRa'''Ra''' wherein Ra''' is the same or different and CLG-l -12- .
is ~ or alkyl of from one to three carbon atoms whlch may be substituted with an OH or R2 and R3'' when taken together may be ethylene or may for~
~(C~2)n' ~ i\
B''' -(C~2)~n' ' wherein n''' and m''' may be tne same or different and are one or two provided that the s~m of n''' and m''' is three or our, and 3''' is a direct bond, O, S, or N-R~ wherein R4 is H or alkyl of from one to four carbon atoms; Z''' is alkyl of from one to four carbon atoms which may be substituted with an SRl , or ORl group wherein Rl is de~ined above, or ~" 'NR2 R3 wherein D" ' is alkylene of ~rom two to four carbon atoms which may be substituted with an OH group and R2 and R3 are as defined above; and the pharmaceutically acceptable salts thereof.
The invention in a seventh subgeneric aspect OL
its fourth chemical compound aspect is a compond haviny the structural formula I " "
N - I-Z'''' OH o NR''''Y'''' I'''' wherein R'' " is H or alkyl of from one to six carkon atoms; '~" '' is H, alkyl of from one to si~ carbon atom~ which may be substituted with an oRi group wherein Rl is H or alkyl of from one to four carbon atoms, or A''''NR2 R3 wherein A'''' is alkylene of ~rom two to four carbon atoms, R2 and R3 may be the same or diLferent and are H, alkyl of from one to six ~L~5~
CLG-l -13-carbon atoms which may be substituted with an O~ or an NRa''''Ra''i' whe~ein Ra'l'' is tne same or different and is H or alkyl of from one to three carbon atoms which may be substituted with an OH or 22 and R3 when taken together may be ethylene or mav .orm -(cH2)n B''' ~(CH2)m~
wherein n'''' and m'''' may be the same or different and are one or two provided that the sum of n' " ' and m'''' is three or four, and B " '' is a direct bond, O, S, or N-R~ wherein R4 is ~ or alkyl of from one to four carbon atoms; Z " '' is al~yl of from one to four carbon atoms which may be ~ubstituted with an SRi ', or oRi ' group wherein R¦ is defined above, or D " ''NR~ R3 wherein D" " is alkylene of from two to four carbon atoms which may be substituted with an O~ group and R2 and ~3 ' are as defined above; and the pharmaceutically acceptab1e ~alts thereof.
The invention in an eighth subgeneric aspect of its fourth chemical compound aspect is a compound haviny the structural formula I~
N - N_zv ~ ~ ' NRVyv IV

5 ~ ~ L~

CLG-l -14-wherein E~v is H or alkyl of from one to six car~on atoms; yv is Fl, alkyl of from one to four carbon atoms or AVNR2VR3v wherein Av is alkylene of from two to four carbon atoms, R2Vand R3v may be the same or different and are H or alkyl of from one to six carbon atoms which may be substituted with an OH or R2V and R3v when taken together may be ethylene or may form -(CH2)n -(C~2)mV/
wherein n~ and mV may be the s2me or different and are one or two provided that the sum of nV and mV is three or four, and Bv is a direct bond, 09 S7 or NR4V wherein R4v is H or alkyl o~ from one to four carbon atoms; zv i9 alkyl of from one to four carbon atoms, which may be substituted with an SRlV, or ORlV group wherein RlV is H or alkyl of from one to four carbon atoms, or DVNR2VR3v wherein Dv is alkylene of from two to four carbon atoms which may be substituted with an OH group and R~v and R3v are defined above; and the pharmaceutically acceptable salts thereof.
The invention in a ninth subgeneric aspect of its fourth chemical compound aspect is a compound having tne structural formula IVi N - N-ZVi GH ~ NRViyvi Ivi CLG-l -15-wherein RVi is ~ or alkyl o~ from one to six car~on atoms; ~vi is H, alkyl of from one to four carbon atoms which may ~e substitu~ed with an oRlVi group wherein Rlvi is ~ or alkyl of from one to four car~on atoms or Avl~R2vlR3vl wherein ~vi is alXylene of from two to four carbon atoms R2qi and R3Vi may be the same or different and are alkyl of from one to six carbon atoms which may be substituted with an OH, or R2Vi and R3Vi when taken -together may ~e ethylene or may form -(CH2)nvi\
3vi -(CH2)mvi/
wherein n~Jl and mVl may be the same or different and a-ce one or ~wo provided that the sum of nvi and i i~ three or four, and BVi is a direct ~ond, O, St or NR4Vi wherein R~Vi is H or alkyl of ~rom one to four carbon atoms; ~vi is DVlNR2vlR3vl wherein ~vl is alkylene o~
from two to four carbon atoms r R2Vi and R3Vi are defined above; and the pharmaceutically acceptable salts thereof.
The invention as species of the fi~st generic chemical compound aspect of the invention are the chemical co~pounds having the following names:
2-[2-(diethylamino)ethyl)]-5-[[2-[(2~hydroxyethyl)-amino]ethyl3amino]anthra[1,9-cd]pyrazol-6(2El)-one;
2-[2-~(2-hydroxyethyl)amino~ethyl3-5-[[2-[(2-hydroxy-ethyl)amino]ethyl3amino]anthra[1,9-cd]pyrazol-6(2H)-one;
5-[(2-aminoethyl)amino]-2-[2-[(2-hydroxyethyl)amino]-ethyl]anthra[l,9-cd]pyrazol-6(2~)-one;
2-[2-~diethylamino)ethyl]-7,10-dihydroxy-5-[[2-~
hydroxyethyl)amino]ethyl]aminoJanthra[1,9-cd]-pyrazol-~(2H)-one;

CLG-l -16-5 [[2-[(2-hydroxyethyl)amino]ethyl]amino~-7,10-dihyaroxy~2-(2-hydroxyethyl)anthra[l,9-ca]pyrazoi-6(2H)-onej 2-~2-~[2~(dimethylamino)ethyl]amino]ethyl~-5-[[2 [(2~
hydroxyethyl)amino]ethyl]amino]-7,10-dihydroxyanthra-~l,9-cd]pyrazol-6(2H)-ane;
Z-[2-(diethylamino)ethyll-[[2-(4-morpholinyl)ethyl)J-amino]anthra[l,g-cd]pyrazol-6(2H)-one;
2-(2-aminoethyl)-5-[[2-[(2-hydroxyethyl)amino]ethyl]-amino]anthra[l,9-cd]pyrazol-6(2~)-one;
5-[~2-aminoethyl)amino]-2-[2-(diethylamlno)ethyl]-7,lQ-dihydroxyan~hra[1,9-cd]pyrazol-6(2~)-one;
2-[2-~diethylamino)ethyl]-7,10-dihydroxy-5-[[2~
~methylamino~ethyl]amino]anthra[1,9-cd]pyrazol-6~2H)-one;
2-[2-(dimethylamino)ethyl]-7,10-dihydroxy-5-[[2-[(2-hydroxyethyl)amino]e~hyl]amino]anthra[l,9-cd]pyrazol-6(2_)-one;
5-~2-aminoethyl)amino]-2-[2-~dime~hylamino)ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
5-[~3-aminopropyl)amino]-2-[2-(dimethylamino)ethyl]-7,10-dihydroxyanthra[1,9-cd]pyrazol-6(2H)-one;
5-[(2-aminoetnyl)amino]-7,10-dihydroxy-2-(2-hydroxy-ethyl)anthra[l,9-cd]pyrazol-6(2H)-one;
5-[[2~~dimethylamino)ethyl]amino]-7,10-dihydroxy-2-(2-hydroxyethyl)anthra[l,9-cd]pyrazol-6(2H)-one;
2-~3-(diethylamino)-2-hydroxypropyl~-7,10-dlhydroxy-5-[[2-[(2-hydroxyethyl)2mino]ethyl]amino]anthra [l,9-cd]~pyrazol-6(2H)-one;
5-[(2-aminoethyl)amino]--2-[3-(diethylamino)-2-hydroxy-propyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
2-[3-(dimethylamino)propyl]-7,10-dihydroxy-5-[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthra[l,9-cd]-pyrazol-6(2H~ one;

CLG-l ~17-7,10-dihydroxy-5-[[2-[(2-hydroxyethyl)amino]ethyl]-amino]-2-[2-[(2 hydroxyethyl)methylamino]eLhyl]-anthra[l,9-cd]pyrazol-6(2H)-one;
7,10~dihydroxy-5-[[2-[(2-hydroxyethyl)a~ino]ethyl]-amino]-2-13-[(2-hydroxyethyl)amino]propyl3anthra-[l,9-cd]pyrazol-6(2~)-one;
5-[(2-aminoethyl)amino]-7,10-dihydroxy 2-[2-[(2-hydroxyethyl)amino]ethyl]anthra[l,9-cd]pyrazol-6(2~)-one;
5-[[2-(dimethylamino)ethyl]amino]-7,10-dihydroxy-2 [2-[(2-hydroxyethyl)amino]ethyl]anth~a[l,9-cd]-pyrazol-6(2H)-one;
5-[~2-tdiethylamino)ethyl]amino3-7,10-dihydroxy-2-[2-~(2-hydroxyethyl)amino~ethyl]anthra[l,9-cd]pyrazol-6(2H~-one;
5-[(3-aminopropyl)amino]-7 r 10-dihydroxy-2-[2-[~2-hydroxyethyl)amino]ethyl]anthraEl,9-cd]pyrazol-6-(2H)-one;
7,10-dihydroxy-2-[2-t~2-hydroxyethyl)amino]ethyl]-5-~[3-[(2-hydroxyethyl)amino]propyl]amino]anthra[l,9-cd]p~razol-6(2H)-one;
5-[[Z-[[2-(dimethylaminoethyl]amino]ethyl~amino]-7,10-dihydroxy-2-[2-[(2-hydroxye~hyl)amino]ethyl]anthr2-[1,9-cd]pyra~ol-6(2H)-one;
5-[[2-1(2-aminoethyl)amino]ethyl]amino]-7,10-di-hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]anthra-[l,9-cd]-pyrazol-6(2H) one;
5-[12-[bis~2-hydroxyethyl)amino]ethyl]amino]-7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl~anthra-[l,9-cd~pyrazol-6(2H)-one;
7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-1[2-(methylamino)ethyl]amino]anthra[1,9-cd~pyrazol-6(~H)-one;

Cr.G-l -18-2-(2-aminoethyl)-7,10-dihydroxy-5-[[2-[(2-hydroxy-ethyl)aminoJethyl]amino]anthra[l,9-cd]pyrazol-6(2H~-one;
2-(2-aminoethyl)-5-[(2-aminoethyl)amino3-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
2-[2-aminoethyl)-5-[[2-[[2-(dimethylamino)ethyl]-amino]ethyl]amino]-7,10-dihydroxyanthra[l,9-cd]-pyrazol-6(2H)-one;
2-(2-am.inoethyl)-5-[[3-[(2-hydroxyethyl~amino]propyl]-amino~-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
2-(2,3-dihydroxypropyl)-7,10-dihydroxy-5-[[2-~(2-hydroxyethyl)amino]ethyl]amino]anthra[l,9-cd]-pyrazol-6(2H)-one;
7-hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-~[2-[(2-hydroxvet.hyl)amino]ethyl]amino]anthra[l,9-cd]
p~frazol-6(2Hl-on~7 7 hydroxy-2-[2-[(2-hydro.Yyethyl)amino]ethyl)-5- E [ 2-(methylamino)ethyl]amino]anthra[l,9-cd]pyrazol-6(2~)-one;
10-Hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-[~2-[(2-hydroxyethyl)amino]ethyl]amino]anthra[1,9-cd]pyra~ol-6(2H)-one;
7,8,10-trihydroxy-2-[2-[(2-hydroxethyl)aminO]ethyl]-S-[t2-[(2-hydroxyethyl)amino~ethyl]amino]anthra-~l,9-cd]pyrazol-6(2H)-one;
7,8,10-trihydroxy-2-[2-[(2-hydroxyethyl)amino)]ethyl]-5-1[2-(~ethylamino)eth~l]amino]anthra[l,9-cd)pyrazol-6(2H)-one;
.5-[[2-[(2-aminoethyl)amino]ethyl]amino]-7,10-dihydroxy-2-(2-hydroxyethyl)anthra[l,9-cd]pyrazol-6(2_)-ore;
2-(3~aminopropyl)-7,10-dihydroxy-5-[[2-[(2-hydroxy-ethyl~aminoIethyl]amino]anthra[l,9~cd3pyrazol6(2H)-one;
2-(3-aminopropyl)-5-[[2-[[2-(dimethylamino)ethyl amino]ethyl~amino]-7,10-dihydroxy anthra[l,9-cd]-pyrazol-6(2H)-one;
/

CLG-l -19-2-(2-aminoethyl)-7~10-dihydroxy-S-[E2-(methylamino)-ethyl]amino]anthra[l,9-cd]pyrazol-6(2H)-one;
5-[(2-aminoethyl)amino]~2-[3--(dimethyla~ino)propyl]-7,10~dihydroxyanthra[1,9-cd]pyrazol-6(2H)-one;
7,8-dihydroxy-2-{2-[(2-hydroxyethyl)amino]ethyl]-5-[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthra[l,9-cd~
pyrazol-6(2H)-or.e; and the pharmaceutically acceptable salts thereof.
The ln~-ention in its f~fth generic chemical compound aspect is a chemical compound having ~he structural formula N N-Z

Q" ~

~herein Q, Q', and Q'' may be the same or different and are hydrogen, OH, alkoxy of one to four carbon atoms, chlorine, benzyloxy, ~-chlorobenzyloxy and p-methoxyben~yloxy; and the pharmaceutically acceptable salts thereof; Z is defined above; and the pharmaceutica'ly acceptable salts thereof; provided that when Q = Q' = Q'' = H, Z may not be H or CH3.
The invention in its sixth generic chemical compound aspect is a chemical compound having tne structural formula III
[~$
Q~ o Cl III

CLG-l -20-wherein Q and Q' may be the same or different and are H, OH, Cl 4alkoxy, benzyloxy, p-chlorobenzyloxy, or o-meLhoxybenzylo~y and Z is define~ above; and the pharmaceutically acceptable salts thereof; provided that ~hen Q = ~' = H~ Z may not be H or CH3~
The invention in a first subgeneric: aspect of its sixth chemical compound aspect ls a che~ical compound ha~ing structural for~ula III wherein Q and Q' are H;
and the pharmaceutically acceptable salts thereof.
The invention in a second subgeneric aspect of its sixth chemical co.npound aspect is a chemical compound having the structural formula III wherein Q
and Q' are benzyloxy, ~-chloroben~yloxy, or ~-methoxybenzyloxy; and the pharmaceutically acceptable salts thereo~O
The invention in a third subqeneric aspect oE its sixth chemical compound aspect is a chemical compound having structural ~ormula III wher~in Q and Q' are O~I;
~nd the pharmaceutically acceptable salts thereof.
The invention as species of the fi~th generic chemical compound aspect of the invention are the chemical compounds having the Eollowing names:
5-chloro-2-~2-(diethylamino~ethyl]anthra[l,9-cd]-pyrazol-6(2H~-one;
5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl~anthraEl,9-cd]pyrazol-6(2H)-one;
5-chloro-2-[2-(diethylamino)ethyl]-7,10-dihydroxy-anthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-7,10-dihydroxy-2-~2-hydroxyethyl)anthra[l,~-cd]pyrazol-6(2H)-one;
5-chloro-2--[2-(diethylamino)ethyl]-7,10-bis(phenyl-methoxy)anthra[l,9-cd~pyrazol-6(2H)-one;
S-chloro-2-[2-[[(4-methylphenyl)sulfonyl]oxy]ethy1]-7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)one;
S-chloro-7,10-dihydroxy-2-[2-[(2-hydroxyethyl~amino]-ethyl]anthra[l,9-cd]pyrazol 6(2H)-one;

~.~5~ .2 CI.G~l -21-5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyll-7,10-bis-~phenylmethoxy)anthra[l,9 cdlpyrazol-6(2H)-one;
5-chloro-2-~2-[[2-(dimethylamino~ethyl]amino]ethyl]-7,10-dihydroxyanthra[l,9-cd~pyrzzol-6(2H)-one;
2-(2-aminoethyl)-5-chloroanthra[l,9-cd]pyrazol-6-(2H)-one;
5-chloro-2-[2-(dimethylamino)ethyl]-7,10-dihydroxyanthra[l,9-cdjpyra~ol-6(2H)-one;
5-chloro-7-~3-(diethylamino)-2-hydroXypropyll-7,10-dihydroxyanthra[1~9-cd]pyrazol-6(2H)-one, 5-chloro-2-[3-(dimethylamino)propyl]-7,10-dihydroxyanthra[l,9-cd~pyrazol-6(2H)-one;
S-chloro-2-~2-hydroxyethyl)-7,10-bis(phenyl-methoxy)anthra[l,9-cd]pyrazol-6~2H)-one;
5-chloro-7,10-dihydroxy-2-[2-~(2-hydroxyethyl)-methylamino]ethyl]anthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro 2-[7.-[(2-hydroxyethyl)methylamino]ethyl]
7,10-bis~phenylmetho.xy)anthra[1,9-cd]pyrazol-6(2H)-one;
5-chloro-7,10-dihydroxy-2-[3-[(2-hydroxyethyl)-amino]propyl]anthra[l,9-cd]pyraæol-6(2H)-one;
5-chloro-2-[3-~(2-hydroxyethyl)amino]propyl~7,10-~is(phenylmethoxy)anthra,l,g-cd]pyrazol-6(2H)-otle;
5-chloro-2-[3-[[4-methylphenyl)sulfonyl]oxy]-propyl]-7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-(3-hydroxypropyl)-7,10-bis(phenyl-~ethoxy)anthra[1,9-cd~pyrazol-6(2H)~one;
2-~2-a;ninoethyl)-5-chloro-7,10-dihydroxyanthra-~1,9-cd]pyrazol-6(2H)-one;
2-(2-aminoethyl)-5-chloro-7,10-bis(phenylmethoxy)-anthra[l,9 cd]pyrazol-6~2H)-one;
5-chloro-2-[(2,2-dimethyl.-1,3-dioxolan-4-yl)-methyl]-7,10-bis(phenylinethoxy)anthra[l,9-cd]-pyrazol-6(2~)-one;
5-chloro 2-~2-~(2-hydroxyethyl)amino]ethyl]-7-(phenylmethoxy)anthra[l,9-cd]pyrazol-6(~H)-one;
.) ~s~

CLG-l -22 5-chloro-2-[2-[(2 h-ydroxyethyl)amino]ethyl]-10-(phenylmetlloxy)anthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-[2-[(2-hydro~yethyl)amino]ethyl]-7,8,10-tris(phenylmethoxy) anthra[1,9-cd~pyrazol-6(2M)-one;
2-(3-aminopropyl)-5-chloro-7,10-bis(phenylmetho~y)-anthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl~-7,8-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one;
5 chloro-2-[2-[[2-(dimethylamino~etllyl]amino]ethyl}-7,10-bis(phenylmethoxy)anthra[1,9-cd]pyraæol-6(2~)-one; and the pharmaceutically acceptable salts thereof.
The invention in its seventh seneric chemical compound aspect is a compound having the structural formula IV
N N-Z
$3~
NRY O
IV
wherein R is H or alkyl of from one to six carbon atoms; '~ is H, alkyl or from one to six carbon atoms which may be substituted with an P~l group whereir R
is H or alcyl of from one to six carbon atoms, or A~R2R3 wherein A is alkylene of from two to eisht carbon atoms, R2 and R3 may be the same or different and are H, alkyl of rom one to six carbon atoms which may be substituted with OH or an NRaRa wherein Ra may be the same or different and is H or alkyl of from one to ~hree carbon atoms which may be substituted with OH, cr R2 and R3 when taken tosether may be ethylene or may form ChG-l -23--(CH2)n \
B
~(C~2)m/
wherein n and m may be the sa~e or di~ferent and are one, t~o, or three, provided that the sum of n and m is an integer of from three to six, and B is a direct bond, O, S, or N-R4 wherein R4 is H or alkyl of from one to si~ carbon atoms; R and Y when ~aken together may be ethylene or may form -(CH2)n\
B

~(cH2~m/
wherein n, m, and B are defined above; Z is H, alkyl of rom one to six carbon atoms which may be su~stituted ~ith an N(Rl)2, SRl, or ORl group wherein Rl may be the same or difEerent and is deEined above, or DNR2R3 wherein D i9 alkylene of Erom two to eight carbon atoms which may be substituted ~ith an OH group and R2 and ~3 are as defined above; and the pharmaceutically acceptable salts thereof; with the following provisos, 1) ~hen Z
is H, R and Y when ta~en together do not complete a piperidine ring, 2) when Z is CH3, R and Y when taken together 20 not complete a piperidine ring or a morpholine ring.
The invention as species of the seventh generic chemical compound aspect of the invention are~the chemical compounds having the following names.
2-[2-(diethylamino)ethyll-7-[~2-[(2-hydroxyethyl)-a~ino~ethyl]amino]anthra[l,9-cd]pyrazol-6(2H)-one;
2-~2-(diethylamino)ethyl-7-1[2-(dlethylamino)ethyl]-amino]anthra[l,9-cd]pyrazol-6(2~)-one;
2-[2-~(2-hldroxyethyl)amino]ethyl]-7-[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthra[1,9-cd]pyrazol-6-(2H)-one; and the pharmaceutically acceptable sal.s thereo f .
J

The invention in its eighth generic chemical compound aspect i5 a compound haYing the structural formula VII
N - I-Z

VII
wherein Z is defined above, provided it is not H or CH3, The invention as a species of the eighth seneric ch~mical compound aspect oE the invention is the chemical compound having th~ fo~lowiny names:
7-chloro-2-~2-(diethylamino)ethyl]anthra[l,9-cd]-pyrazol-6~2H)-one;
7-chloro-2-[2-[(2-hydrox~ethyl)amino]ethyl~anthra[l, 9-cd]pyra201-6(2H)-one; and the pharmaceutically - - -accep~able salts thereof.
The invention in its ninth chemical compouna aspect is 5,8-dichloro-1,4,9,10-anthracenetetrone.
The invention in its tenth chemical compound aspect is the compound 2-[(hydrazinoethyl)amino]
ethanol and the acid addition salts thereof.
The invention in its first generic chemical process aspect is a process Eor preparing a compound having the structural formul~
X ~ Z
W-~

X o NRY

which com~rises reacting a compound haviny the s tructural formula f~
CLG~ 25~

N - N-Z

~G C~

with an amine ha~ing the formula HNRY wherein W, X, X', ~, Q', Q'', Y, Z, and R are deined above and, when necessary~ removing by catal~tic hydrogenation or by treatment with boron tribromide or trichloride any ben~l groups.
The invention in its second generic chemical process aspect is a process Eor preparing a compcund ha~ing structural ~ormula I
N - N-Z

X' o NRY
I

which comprises reacting a compound having structural f ormula II
~$
Q~ o Cl II

~.5~
CLG-l -26-with an amine having the 'ormula HNRY ~herein X, X', Q, Q', Y, Z, and R are defined above and, when necessary, removing by catalytic hydrogenation or by treatment with boron tribromide or boron trichloride any ben~yl groups.
The invention in a first subgeneric aspect of its second chemical process aspect is the process defined above wherein X and X' are OH.
The invention in a second subgeneric aspect of its seco~d chemical process aspect is the process definecl above wherein X and X' are H~
The invention in its third generic chemical process aspect is a process for preparing a compound having structural formula III
Q N - N-Z

.' ~1, Q' Cl III
which comprises reacting a compound having formula V
Q o Cl ¢~
Q~ o Cl V

with a hydrazine having the formula H2N-NHZ, wherein Q, Q' and Z are defined above.

-~S~f~

C'G-l -27-The invention in a first su'ogeneric aspect of its thi~d chemical process as~ect is the process defined above wherein Q and Q' are benz~loxy, p-chlorobenzyloxy, or p-methoxybenzylo~y.
The inqention in 2 second subgeneric aspect of its third chemical process aspect is the process defined above wherein Q and Q' are OH.
The invention in a third subgeneric aspect of its third chemical process aspect is .he process definec~
above wherein Q and Q' are H.
The invention in its fourth generic chemical process aspect is a process for preparing a compound having structural ~ormula IV
N ~-Z
~ '' NRY o I-~

which comprises reacting a compound having structural formula VIT
N ~-Z
~1 ` ~
Cl o VII

with an amine having the formula HNRY, wherein Y, Z, and R are defined above.

~5~ 2 CLG-l -28-The invention in its fifth chemical 2rocess aspec~ is a process for preparing 5,8-dichloro-1,4,9,10-anthracenete~rone which comprises reacting 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione with lead tetracetatet The invenkion in its sixth chemical process aspect is a process for preparing 2-[(hydrazinoethyl)amino3ethanol ~hich comprises reacting hydrazine with N-~2-hydroxyethyl)aziridine.
The in~ention in its ~irst pharmaceutical composition aspect is a pharmaceutical composition comprising a compound having structural formula I and the phar~aceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier.
The invention in its second pharmaceutical composition aspect is â pharmaceutical composition comprising a compound having structural formula I' and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier.
The invention in its third pharmaceutical composition aspect is a pharmaceutical composition comprising a compound having structurâl formula Il' and the pharmaceutically acceptable salts thereo~ in co~bination with a pharmaceutically acceptable carrier.
The invention in its ~ourth pharmaceutical composition aspect i3 a pharmaceu-tical composltion comprising a compound havina structural formula I''' and the pharmaceutically acceptable salts thereo in combination with a pharmaceutically acceptable carrier.

~,~,5~ 'LL~

CLG-l -29-The invention in its fifth pharmaceutical com-position aspect is a pharmaceutical composition com-prising a compound having structural formula I'''' and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier.
The invention in its sixth pharmaceutical com-position aspect is a pharmaceutical composition com-prising a compound having structural formula Iv and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier.
The invention in its seventh pharmaceutical com-position aspect i9 a pharmaceutical composition ~-om-pris;ncJ a compound having structural eormula I~i and the pharmaceu~ically acceptable salts thereof in combination with a pharmaceutically acceptable carrier.
The invention in its eighth pharmaceutical composition aspect is a pharl~aceutical composition comprising a compound having structural formula IV
and the pharmaceu.ically acceptable salts thereof in combination wilh a pharmaceutically acceptable carrier.
The invention in its first pharmaceutical method aspect is a method for treating microbial infections in a mammal which comprises administering a ~suEEicient amount of a com~ound having structural formula I and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable czrrier to a mammal in need thereof.
The invention in its second pharmaceutical method aspect i~ a method for tr~ating leukemia in a mammal which comprises administering a sufficient amount of â
compound having structurâl Lormula I' and the pharmaceutically acceptable sal.s thereof in 5 ~" 1, h ~

combination with a pharmaceutically acceptab:Le carrier, to a mammal in need thereof.
The invention in its third pharmaceutical method aspect is a method for treating leukemia in a mammal which comprises administering a sufficient amount of a compound having structural formula I'' and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier, to a mammal in need thereof.
The invention in its fourth pharmaceutical method aspect is a method for treating solid tumors in a mammal which comprises administering a sufficient amount of a compound having structural formula I''' and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier, to a mammal in need thereoE.
The invention in its fifth pharmaceutical method aspect is a method for treatiny solid tumors in a mamma]. which comprises administering a suEficient amount of a compound having structural formula I'''' and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier, to a mammal in need thereof.
The invention in its sixth pharmaceutical method aspect is a m~thod for treating solid tumors in a mammal which comprises administering a sufficient amount of a compound having structural formula IV and the pharmaceutically acceptable salts thereof in combination with a pharmaceuti-cally acceptable carrier, to a mammal in need thereof.
The invention in its seventh pharmaceutical method aspect is a method for treating solid tumors in a mammal which comprises administering a sufficient amount of a compound having structural formula IViand the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier, to a mammal in need thereof.

f~-rl~r CLG-l -31-The inven~ion in its eighth pharmaceutical method aspect is a method for treating solid tumors in a mam.mal which comprises administering a sufficient amount of a compound having structural formula I'J
and the pharmaceutically acceptable salts thereof in combination with a pharmaceu~ically acceptable carrier, to a mammal in need thereof.

~5~
CLG-l -32-DESCRI3?TION OF THE: P~EFERRED E~;~IBODIMENTS
The co~pounds of the invention may be prepared conven~ently by the follGwing reaction sequence Q ~ A

~ III
I

N N-~ N - N-Z

W ~ B
X O NRY X~ O Cl I II

The reaction step "A," involves the reaction of compound V and a suitably substituted hy2razine, NH2-N~I~ wherein Q, Q' and Q " , and Z are defined hereinabove. This reaction may be accomplished in any of a variety of reaction inert solvents by mixing api~roxi-mately equimolar amounts of compound V and the desired hydrazine in tne chosen solvent at elevated temperature. Use of a catalyst-such as potassium fluoride or of a slight molar excess of the hydlazine reactant may improve a particular yield. Examples of suitable solvents are `~ -dimethylLormamide, dimethylsulfoxide, pyridine, acetonitrile, the cellosolves, and the li`~e. Pyridine is the preferred solvent, suitable reaction temperatures are from aoout !

CLG-l -33-30-8S~C. In general, the reaction is allowed to proceed for about six to about 24 hours at which time the reaction is substantially complete. The completeness o~ a particular reaction may be measured by ~nown procedures such as thin layer chromatography for example. It is generally observed that increasing the reaction temperature will decrease the time necéssary for completing the reaction. The proper choice of the ~eaction ~Jariables is within the s~ill of the art. The products of the reaction are isolated and purified by standard procedures. For example, the reaction ~ixture may be concentrated by evaporating the solvent and the residue may be partitioned between water and a convenient nonwater-miscible organic solvent such as chloroform~ ~enzene, dichloromethane, and the like. The solvent may then be evaporated and the residue may be chrornato~raphed, ~or example, on silica gel. Choice of the proper chromatography solvent is within the skill of the art. After chromatography, the product may be recrystallized, if desired. When the Q, Q', and Ql substituents of the so produced compound III comprise benzyloxy, p-chlorobenzyloxy, or ~-methoxyben2yloxy, the benzyl substituents may be removed, for example, by treatment with boron trichloride or boron tribromide in a chlorinated hydrocarbon solvent such as dichloromethane at about 0C to produce compound II
wherein the corresponding X substituents represent h~droxyl~ Acid addition sal~s may also be prepared by standard procedures. For example, a hydrochloride salt may be prepared by dissolving the free base in a convenient solvent such as 2-propanol and treating this solution with a solution of hydrogen chloride in 2-propanol. The acid addition salts may be recon~erted to the respective free base by treatment with a dilute solution of sodium hydroxide or potassium carbonate for example.

CLG-l ~34~
The reaction step ~'a~ involves the reaction of compound II with a suitably substituted amine HNRY
wherein R, W, X, Xl, y, and Z are defined heceinabove.
This reac~ion nay be ~ccomplished in any of a variety of reaction in~rt solvents by mixing approximately equimolâr amounts of compound II and the desired amine in the chosen solvent at elevated temperature. The use of a slight molar excess of the amine reactant, an inert atmosphere and a catalyst such as anhydrcus cuorous chloride may improve a particular yieid. The use of these variations for a particular reaction is optional and is within the s~ill of the art. Examples of suitable solvents are N,N'-dimethylformamide, dimethylsulEoxide, pyridine, acetonitrile, the cellosolves, and the like. Suit~ble reaction temperatures are from about 85-130C. This reaction has been o~served to proceed particularly efficiently in refluxing pyri.dine. I~ general; the reaction ls allowed to proceed ~or about 6 to about 24 hours at which time it is substantially complete. The completeness of a particular reaction may be ~easured by known procedures such as thin layer chromatography ~or example. It is generally observed t~.at increa~ing the reaction tem?erature will decrease the time necessary for co~pleting the reaction. The proper choice of the reaction variables is within the skill of the art. The products of the reaction are isolated and puriEied by s-tandard procedures which are substantially identical to those described above for compound II. Likewise, acid addition salts of compound I may be prepared by standard procedures such as that described hereinabove for compGund II.
Alternatively, the compound of formula IIi ~ay be ~reated directly with an amine of formula HNRY to produce a compound of the Eor~ula ~.5~
CLG-l -35~

N - N-Z

` Q~ ~ ~ ~

Ql b NRY

This compound may then be debenzylated by a standard procedure to produce the corresponding compou~ld 'naving structural formula Io In an alternate process the compounds of formula I wherein X and X' are hydro~y may be prepared by the reaction of compound VI (compound V wherein Q and Q' are d;hydroxy OH O Cl VI

with a suitably substituted hydrazine WH2-NHZ to produce a compound of structural formula II wherein is OH; Z is defined hereinabove. The reaction of VI
~nd the hydrazine may be accomplished by mixing approximately equimolar amounts of the reactants in a solvent such as ~,N-dimethylformamide, dimethylsulfoxid2, pyridine, and the like at temperatures about 30-90C~ preferably 30-60C, in the presence of a base such as potassium bicarbonate.
Pyridine is the preferred sol~ent and when utilized does not require an additional base. The use of catalyst such as potassium fluoride may improve ~'5'~ 2 CLG-l -36- -~he yield of a particular reaction. The subsequent conversion of the so produced compound II ~herein X and X7 are hydro~y to the corresponding compound is carried out as already described hereinabove 2S
reaction step "8".
In an alternate method for prepari.ng the compounds of formula III, a compound of formula V is reacted ~ith a hydroxyalkylnydrazine of tne for~ula NH2-NH(CH2)2-ll-OH, preferably NH2-NH(CH2~2-3-O~
to produce a compound of formula III wherein ~ is -(C~2)2-ll-~ and is pre erably -(CH2)2-3-OH-This reaction is carried out substantially as described hereinabove as reaction step "An. The OH
group of the Z substituent is then derivatized to produce an easily displaceable substituent known to those skilled in the art as a "leaving group". ~or example, the O~ group may be converted to a tosyloxy or mesyloxy group by reaction wi.th respectively p-toluenesulphonylchloride or methanesulphonylchloride in pyridine by procedures ~nown to those skilled in the art. The leaving group, so produced, may be subsequently displaced with, for exam~le, an amine such as diethylamine to produce a Z substituent of the structure -~C~2)2~ll-NEt2. In the preferred procedure the substituent ~ so produced is -~CH2)2_3NEt2. The benzyl aroups or substituted benzyl groups of compound III, if present, arè removed as described above to produce a compound o ~ormula ~I, which may be converted to a compound of formula I
as already described hereinabove as reaction step '!B".
The compounds.having structural formula I wherein X and X' are chloro are prepared starting from compound VI by first converting VI to the corresponding di-~-toluenesulfonic acid ester VI'.

CLG-l -37-Cl O OTos Cl o OTos VI' ~ his conversion is conveniently carried out by treating VI with ~-toluenesulfonyl chloride in a nonreactive solvent such as ace~onitrile at reflux temperature. The diester VI' is then treated with a substituted hydrazine ~H2N~Z substantially âS
described above for the conversion of compound V to compound III. The product of this reaction, VI "

Cl N - N-Z

'' ~3~3 ,, Cl O OTos ~II"

is then treated with an amine having the for~ula HNYR
substantially as described above Lor the conversion of compound II to compound I. The product of this reaction has the follo~ing structural formula.

J~ 1 Cl o NRY
wherein ~, Y, and Z are âS deined hereinabove.

The compounds having structural formula IV are prepared by reacting a compound having structural formula VII with an amine having the formula HNP~Y using substantially the same reaction conditions described above for the conversion oE
compound II to compound I, i.e., reaction step "B". A
particular Z substituent, for example, CH2CH2OH may also be derivatized and converted to another particular Z
substituent, for example CH2CH2NEt2 in a similar manner to the procedure already described hereinabove.
The compounds of s-tructural formula VII are prepared by reacting a suitably substituted hydrazine, NH2-NHZ, wherein Z is defined hereinabove, with 1,5-dichloro-9,10-anthracenedione in a manner substantially identical to that described above for converting compound V to compound III, i.e., reaction sequence "A".
The present invention also contemplates the novel hydrazine, 2-[(hydrazinoethyl)amino]ethanol, ~H2NHCH2CH2NHCH2CH2OH. This novel hydrazine is a useful intermediate for -the preparation of a variety of final compounds of the invention. This novel hydrazine may be prepared by a variety of procedures which are considered equivalent for purposes of the invention. One such procedure involves the reaction of hydrazine and ~-(2-hydroxyethyl)aziridine in an aqueous medium at reflux temperature. The novel 2-[(hydrazinoethyl)amino]ethanol so produced is isolated by standard procedures as a clear liquid which has bp 120 C at 0.035 mmHg. The novel 2-[(hydrazinoethyl)amino]ethanol forms acid addition salts with organic and inorganic acids such as hydrochloric, hydrobromic, sulfonic, phosphonic, methanesulfonic, acetic, benzoic, and the like. For purposes of the invention, such salts are considered equivalent to the free base form of the novel hydrazine.

f~

The benzylated ethers V wherein any of the Q
subs-tituents represent benzyloxy, p-chlorobenzyloxy, or p-methoxybenzyloxy may be prepared by treating compound V
wherein any of the Q substituents represent OH with the corresponding benzyl bromide or benzyl chloride in a convenient nonreactive solvent such as acetone, dimethylsulfoxide, ~,N-dimethylformamide, and the like. The use of a hydrogen halide acceptor such as an alkali metal carbonate (e.g., potassium carbonate) for this reaction is preferred.
The novel intermediate, 5,8-dichloro-1,~,9,10-anthracenetetrone may be prepared by oxidation of 5,8-dichloro-1,4-dihydroxy-9,lO-anthracenedione. The reaction may be carried out with lead tetracetate in glacial acetic acid at or near room temperature.
The 1,4-dichloro-9,10-anthracenedione, compound V
wherein Q = Q' = Q'' = hydrogen, may be prepared by known methods, see for example ~. Am. Chem. Soc., ~8; 3198 ~1926).
The 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione, compound VI, may be prepared by known methods, see for example US Patent No. 3,631,074.
The compound 1,5-dichloro-9,10-anthracenedione, which is utilized to prepare the compounds of formula VII is commercially available or may be prepared by methods known to those skilled in the art, see for example Beilstein 7, 787.
The compounds of the invention form pharmaceutically acceptable salts with both organic and inorganic acids.
Examples of suitable acids for salt formation are hydrochloric, sulfuric, phosphoric, acetic, citric, oxalic, malonic, salicylic, malic, fumaric, succinic, ascorbic, maleic, methanesulfonic, isethionic, lactic, gluconic, glucuronic, sulfamic, benzoic, tartaric, pamoic, and the like. The salts are prepared by contacting the free base form with an ., CLG-l -40-equivalent amount of the desired acid in the conventional manner~ The free base forms may be regenerated by treating the salt form with a base.
For example, dilute a~ueous base solutions may be utilized~ Dilute aqueous sodium hydroxide, potassium carbonate, a~monia, and sodium bicarbonate solutions are suitable for this purpose. The free base forms aiffer from their respective salt forms somewhat in certain physical pr~perties such as solubility in polar solvents, but the salts are otherwise equivalent to their respective free base forms for purposes of the invention.
The compounds of the invention can exist in un-solvated as well as solvated forms, including hydrated forms~ In general, the solvated forms, with pharmaceutically acceptable solvents such as water, et~anol and the like are equivalent to the unsolvated forms for purposes of the inv~ntion.
The term halogen is intended to include fluorine, chlorine, bromine, and iodine.
The alkyl and alkoxy groups contemplated by the invention, unless specified otherwise, comprise both straight ar.Z branched carbon chairs of from one to about six carbon atoms. Representative of such groups are methyl, ethyl, isopropyl, butyl, pentyl, 3-methyl-pentyl, methoxy, ethoxy, i-propoxy, t-butoxy, n-hexoxy, 3-methylpentoxy, and the like.
The alkylene groups contemplated by the inven~
tion, unless specified otherwise, comprise both straight and branched carbon chains of ~rom two to about 11 carbon atoms. Representa.ive of such groups are ethylene, npropylene, n-butylene, n-heptalene, i-propylene, 3-ethyl-1,5-pentalene, 3-propyl~
1,6--hexalene, and the like. The preferred alkylene groups of the invention have the following structural formulas:

CLG--1 ~41-l H3 CH3 CH3 CH3 C2H5 (CH2~-2~ CH-CH2 ; -C~2--c~ ; -CH--CE~-; CH-CH2-C2H5 l ~I3 CH3 CH3 2 ; C~l CH2 C~2; -CH2-c~-c~2-; -cH2-cx2-cH-Certain substituents, such as alkyl or alkylene subs-tituents contemplated by the invention are defined as possibly being substituted with additional substituents, e.g., NH2. Those skilled in the art will recognize that certain combinations of such substituents are ]nost probably unstable and these are not intended to be included wi~hin the scope of the de~lni~ions. For example, an ~-aminoalkyl or alkylene ~Jroup of the general formula = N-CH-NH2 would not be expected to be stable whereas the - corresponding dialkylated substituent = N-CH-N~Alk)2 is e~pected to be stable and is intended to be included within the definitions~ It is within the s~ill of the art to recognize these and other such substituents which are possibly unstable~
The compounds of the invention are new chemical substances of value as pharmacological agents for the treatment of bacterial and fungal infections in warm-blooded animals. They may also be utilized as antiseptic agents such as for use in the sterilization of labora'cory glasswars etc, The antibacterial and an~ifungal activity of representative compounds of the inven~ion ~as established by the screening procedure described belowO

, . ~1., ;2 ~S ~. ~ L~y 2 CLG-l -42-1. Pre~aration of inocula .
IA) Bacteria and yeast-The bacterial and yeast isolates are ~aintained in agar slants or in li~uid media, hereby designated as inoculum media~ The cultures are transferred at regular intervals in such media. (See Table for the correspon-ding inoculum media o each culture.~ The organisms are generally transferred on to agar slants or liquid inoculum media and incubated overnight (18-20 hours): 37C for the bacterial isolates and 28C for the Eungal cultures.
The microbial cells from the overnight agar slants are then scraped o~f ancl suspended in sallne solution (0.85~ NaCl). The microbial concentratlons are adjusted to a light transmittancy of 20-35~, Junior Coleman Spectrophotometer (555 M ). For the organisms that are maintained in liquid media, an ali~uot of the culture suspension is simply diluted with saline to 20-35% light transmittancy.
The above microbial suspension serve as in-ocula for tne assay plates. Thus, 0.16-10 ml (see Table for exact amount) are used to inoc~late 100 ml of the ~olten-agar assay medium.
(B) Mycelial fungi:
~he Penicillium avellaneum is grown for six .
days, at 28C, on an agar medium. This is to allow sporulation of the culture. The organism is then harvested by scrapilg of the cells from the agar surface (mycelia and spores~ and suspending them in saline solution containing 0.05% Tween 80.

*trade mark CLG~l -A3-The suspension is adjusted to a light trans-mitancy of 20~. One ml of this suspension is used to inoculate lOO ml of the molten-agar assay medium.
20 Preparation of assay 2~ates Stainless steel frames, 12.3 x 25.3 cm (ID) and glass plates, 15~3 x 31.7 cm are used to make the test trays. The frames are attached to the plates with tape at each end and the inner edges sealed with 2~ agar. Twenty five ml of inoculated assay medium is spread evenly on each tray and allowed to soliaify. The trays are covered, inverted, and refrigerated until used.
3. Disking of samples The compounds or samples to be tested are dis-solved in suitable solvents, e.g., alcohols, dimethylsulfoxide, or N,N-dimethylformamide. The samples are generally dissolved so that the final concentration of the solvent i5 <10~ . * The compounds are tested at different concentrations:
3,000; l,OOO; 500; lOO; and lO mcg/ml. Paper discs (1207 m~ diameter) are placed on the agar trays with forceps, then O.OS ml of the dissolved compound is pipetted onto each disc using a 0.2 ml pipette. (*If the co~pound does not stay in solution at <10% alcohol, then the fuli strength alcohol is used. However r the impregna.ed discs are air-~dried before they are laid on to the seeded agar plates.)

4 Inter~retation of results .
The disXed agar trays are incubated overnight (18-20 hours) at 37C for the bacterial cultures and 28C for the yeasts~ The Penicillium avell2neium tray is incubated for at least 20-24 CLG~ 4~
hours since it is a slower-growing orqanism.
Active compounds show a zone o~ inhibition around the disc~ The diameter of the zone is measured in mm. The ~one diameter of active co~.pound~ ranges from a minimum of 13.5 mm to as high as 60 mm.
The size of the zone diameter generally reflects the activity of he compound: the larqer the zone the greater the activity~

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CLG-l -46

5. Culture media The composition of the various culture media, except for the commercially available media, are sho~n below. The co~mercial ready-made Yeal Infusion Medium is obtained from Difco Laboratories, Detroit, Michigan, USA. Add 1.5 agar to these media for use as agar plates.

Glucose 0.2 Sodium Glutamate 1.04 K~2P0~ 0,03 Na2X?0~ 0.07 Salts #la 1 ml Salts ~2~ 10 ml H20 (distilled) asal~s ~ 1 % bSalts # 2 %

MgS04 1.0 MnS0~ 1.0 CaC12 5.0 ZnS04.7H20 1.0 NaCl 5.0 FeS0~.7H20 1.0 CuS04 5~20 0.01 ~2 (distilled) ~2 (distilled) A.~-09 .~ ~2HP4 3.9 gm Dextrose 25 gm Na-citrate 2 H2O 34O4 gm Casein hydrolysate 6,2 gm Asparagine 375 ~-tryptophan 125 mg Cysteine 312,5 my Gluta-thione 3,1 mg Thiamine HCl 250 g Riboflavin 625 g Ca ~antothenate 500 g Nicotinic acid 500 g ~-aminobenzoic acid 625 Bio~in 120 5 9 Pyridoxine HCl 2.5 g Folic Acid 500 g NaCl . 12.5 MgSO~ 250 g FeSO4 12.5 g MnSO4-H2O 125 g Tween 80 62.5 mg H20 (dis~illed) 1000 ml AM 25 %
Na2HPo4 ~ H20 n O35 ~H2P4 0.05 Yeast Extract (Difco) 0.5 Dextrose l,0 Distilled Water Utiliziny the above described procedure, the following results were obtained for representative compounds of the invention.

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C~G 1 -57-In addition to their useralness as antibio~io and antifur.gal agents, cer~ain o the compounds of ~he in vention display in vivo zntileukemic ar~.iv:i~y ~hen tes~ed by th~ following procedure.
The in YiVo lym~hocy~ic leukemia ~3a8 test is carried out by the United Sta~es .~ational t:~ncer Institute. Th~ animals used ar~ eith2r m2le or e~ale C~2Fl miceO There are six to seven animals ~er ~es~
groupO The tumor trar.s~lant i5 ~y l~trap~ri~oneal injection of dil~t~ ascitic ~luid conta.~ing cell3 oE
lymphocy~ic l~ukemia P38~. ~he :es. compounds.are ad,~inister-d in~rap~ritone~lly in t~o single dose~
~ith a fouroda~ interval bet~een dos2s ~t various dos~
levels following tumor inoculation. The anim~ls are wei~hed and survivors are rPcor~ed on a regul2r basis for 30 day~ A ratio of survival ~ime ~or tre~ted (T)/control ~C~ animals is calculated. ~he c_iterion for efficacy is ~/C X 100 ~ 125~. The.positive . .~.
control com~ound in ~hi~ ~e t is 1,4-dihydro~y-5,8-[bis~[2-~2-hydroxyethyl)amin~l-ethyllamino]-9,10-anthrac~nedione given at dosages ranging ~ro~ 12~0 to O.075 mg/Xg. See C2nce~ Chemot~era~Y ~e~orts, Part 3, 3, 1 ~1972) for a compr~hensive di_cussion o~ the Drotoco 1 .
Utilizing this procedur~, the ro'lowiAq results were obta.ned or represen~a~ive co~pounds o~ t.~a invention.

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CLG-! -58-X Z NRY Dose ~/C X iO0 _ mg/kq ( P~r~ent ) _ ~)2~3 2)2NI-~e)21~H~C~2)2Na~c~2)2oHl 12.5 j242, 182

6 25 1 214, 214 j ~2HC1 ~ 1 3 121192, 171 1.561163

7,iO-(CH~2¦(CH2)2N(~e)2iNH(C~2~2NH2 ¦ 6 ~51216 192 2~1C1 1 1 3 ;21 182 173 1.56 l 194, 149 0.781194, 146 (OH)2¦(CH2)2N(Et)2¦NH(CH2)2N(Et)Z ¦100 llaO, 1~4 168 154 ~46 12. 5 1 132, 114, 140 ¦ tc82)2l~(Et) 2¦NHIC82) 2N [cH2)2] 2oi 400 1 211 I 2HCl IILoO 1145, 126 H¦ (CH2)2NlE:t)2¦NH(CH2)2'~H~c~2)2 ¦ ¦

21~C1 1 1 6 251145 146 161, 178 3.121123, 142, 164, 151 1~561 142, 142, 146 ,781135 . __ t ~ ~5~
~--1 ;9 .
X j 3 I NPY Dose ~/C ~ 100 ~ mq/k~ _rcent I
7,10-(OH!2¦ (CH2)2';Ee)2 ¦NH(CH2)2NH(CHZ)2OH¦ 12.5 126~, 212 I ~ 2 H C 1 1 1 3 121164, 164, 165 I I I 1. ;61 14a 149 lSS
0.781140 lSl lS9 ~ I 1 0.391152, 126 7,10-(OH)2l(~72)2N(E )2 INH(cH2)2~yd~e ¦ 25 1219 .ures I I 1 6.251163 3.121154 2HCl ¦ NH ( CH 2) 2NH2 ¦ 12 5 ¦ 280 189 Cures I 1 3.121154, 160 I i 1 1.561172 2J( Z)2 H( ~2)2~(~e)2l~H(c~2)2NH(cH2)2oHl 53 1226 l l 1 12.5 1179,219 I I 1 6 25118~3,191 7,10-~OH)2¦(CH2)2 H(CH2~2 ¦ 3(C 2)2N(Me)2 ¦ 162 z;l179 7,10 - (cH~7l(cH2)2Na(cH2)2oH ¦~[(CH2)212:~Me I 25 llS0 ~¦ (C'12)zNH~C~2)2OH INH~CH2)2 ~ 2 1 12 5 ¦16j 1674 3.1Z1158 *~
CLG--I
--6~--G I Dose T/C :: 100 ____ I _ _ ma/kq I ( Per_ent ) 7,10-(OH)~ cH2)2NalcH2)2oalNH~cd2)2~ ~e)2 ¦ 25 1 a8 Curss 2HC1 1 1 12 5 1220, 250 Cures 3.121165 165 1. 561161 165 I o.7alls2 H¦ (CH2)2:~Hlc'i2)2~HlNB~cH2)2N~Et)2 ¦ 25 1149 2HC1 1 1 12. S 1150, 155, lsa lSO
6.25 l 13a 146 150 ' 142 3.121 143 143 144, ISl 1 1.561138, L33 )21~H2)2~H~C82)20H¦NH~c't2)2N~Ee)2 ¦ so 1241 2HCl I ¦ L2.5 ¦ L77 L90 3 12¦ L4'3, 150 1. ;6 l 131 135 )2l~cH2)2~H~cH2)2oHlNH~cH2)2NHlcH2)2NlMe)2l 50 1200 254 CUres ! 251C1 1 125 1CUra~228,129 . I I l2.5 1157, L79 ~ las 6.25116~ 172 3.121152 163 Hl ~C}l2)2NHlc'l2)2OHlNH~cH2)2NH~csl2)2oH I 50 ¦ 199 C~t3C02H I I L2.5 ¦ 143 La9 L66 6.~51147, 157, 166 3.121138 150 166 .. ' . ~$~
CLG-l -61-X ¦ ~ ~ NRY 1~ / q I (~oreen~) 21 2 Z ( 2)2'i¦NH(C~2)2`;d(c~l2)2~il o ~139 2HC1 1 1 12.5 1153, 177 6. 251206 Cuces 3.121 107, 187 1. 561158, l~a al (CH2)2t;il(c~2)2HlNH(cH2)2 1 25 ,139 2 1 12 . S 1 175, 180 1 6.2511~6, 180 2HC1 1 1 3.121162t 173 1 1.561150 7,1D-(o~J)2i(ca2~2Na(c~2)2otllNH(c~2)2~H2 ¦ 1 561173, 187 Cures 1 0, 78 1 1~32 2HCl I 1 0 . 391 17 5 7,10--(OH)2¦(CH2)2Na~CH,)20~;¦NH(CH2)3t~H(CH2)~OH¦ 6 25¦169, 25~ Cures 1 . 56 1 201, 166 28Cl l I
7,10-(Oa)2j(Ca2)2N~(c~2)2O~lNH(cH2)3NH2 1100 1~3L Cures 2HC1 1 1 25 1 207 ZS0 Cures 12. S 1 177, 190 6. 25 1 165 172 3.121 16~ 165 7,10-(OH)2' (Crl2)2NH~CH2)2oHlNH(cH2)~NH2 ¦100 1172 173 t I I so I L39 165 ~ICl I 1 25 1 150, 152 1 12.5 1139, 145 I I 1 6.251131 3.121 130 7~l~-(oH)2l(cH2)2Na(cH2)2oHlNH(cH2)5NH2 1100 ILSO
1 25 1 127, 127 2HC1 1 1 12.5 1127 .
3 ¦ ?IRY I DO5e 1 ~/C ~. 100 `q/lCq I !?~r~dnc) 2HC1 I:~HICH2)2t~H(C~2)2O ¦ 12 5 1173 177 3.121 1~9, 158 1 1.561139 .2HC1 1 1 12 5 1182 3. 121160 1.5S I 153 7,10-(Ot)2~ 2)2O~e ¦NH(CH2)2NH(C:;2)2OHI1OO 1139, 140 .HC1 1 1 25 1127, 131 12.5 1127 ¦NH(C~2)ZN(Ye)2 1200 l157, 283 C~lres .2RC1 100 225 242 1 25 1153, 157 173 1 12.5 1124 135, 139 7 10-(0H)2~(CH2)20H INH(C~2)2N(Et)2 130O 1~77 7 1O-~OH)2I(CR2)2OH ¦tlH(CR2)2NH(CH2)20H¦200 l196, 271 . HC1 1 1 50 1163 L65 1 25 1165, 187 1 12 5 1158, 163 1 6.251143, 163 _ _ _ ,1 =_ , , ,,, 1. _,,,, _ , _ X ; 7 ¦ NRY I Dose ¦ ~/C X 100 ---- I m~ ( Perc a n t ) 7 10- ( OH ) ~ ( -H ) Od I Ya ( cH2) 2N~'2 1 25 j 146, 154 12.5 1145, 1;1 6. 2S ~ 135 ?'l0-(OH~2t~-t!2~2S~te ¦ 2 2 ( 2)2OH ¦ 16 25~140 ~ 2HCl 7~lo-(cH)2icH2cHoHcH2~y(-t)2 I~H(ca2)2 ( )2 ~ 50 ll3l, l35 1 12.5 1128 7,10-SoH)2lcH2cHoHct2N(Et)2 ¦-IH(ct32)2 ( 2 2 1 6.25¦123 203 I 0,73 l l 32 7,10--(oH)2tcHzcHoHcH2y(-t)2 ¦NH(ca2)2 H2 1 1262 Cur~s 3.12l 166, 182, 202 1 56l157 145 1 0.391135 7~lo-soH)2lMe ¦NH(Ct3z)2NH(CH2)2OH ¦100 ¦1?4 12.5 ll30 149 6,251133 L 55 7,10-(OH)2¦ C112C~12NH2 INIIC~12C'12NH2 1 25 i1;6, 21a 2HCl j 1 12.5 1144, 203, 221 7,10-(oH~2l C32CH2Nr.~e2 ¦ 2 H2CH2NH2 ¦ 12.5 1205, 208 2HC1 1 16.251196 Cures 7,10-(OH)2!~'32CH2CH2N~3e2 ~NHCH2CH2NHCE2CH2OH ¦ 12.5 ¦213, 203 2HC1 1 16.25l185 167 7~lo-(oH)2lc~l2cH(oH)c~l2o~3¦Nr3cH2cH2~yHcx2cH2oH ~400 i281 255 HCl 1. 1200 ; Z18, 213 100 j 20a, 194 Cures 1 25 1184, 166 ? ,10-(OH)2 ICH2CH2CY2NMe2 ~ HCH2CH2CH2NH2 ¦ 25 i 194, 212 2HCl i j 12 5 1173 130 7,10-(OH)2~CH2C112cH2~Me2 ¦NaCH2cH2NH2 i 12.; 1224 Cure~
I 2~1C1 1 1 6,251186 200 3.121191' lao 7,10-(OH)2~CH2C~12~1MeCH2CH20H ¦NaCH2CH2NHC'32CH2OH ¦ 12.5 ¦203 1.6HC1 1 1 6 2511a2 , a SOH)2¦CH2CH2N13CH2CH2OH ¦NH(C92)3N(CHzCH2OH)2l100 i192 7~10--(OH)2~C-32CH2NHCHzCH2OH INHC9 "H NHCH CH NH I 25 l221 22 6.ZS1194 1~7 -64-~
C~~-l . _ _ _ _ NRY ¦Dose ¦ T/C ~ 100 I Imajcq I (P~r-enC) 7,~0-(OH)2 ICff2.H2r;HCH2CH2Off INHCH2'H2~CH2 2 )2 ¦!00 ¦223, 254 .2.3HC1 ¦ 1 50 1203, 169 i j 25 1137 194 ~'1-(#)2 1~2cH2t~Hc~2~H2oH ¦~H(C:~2)3~(cH2)~H(cH2)3r~l2l 12. 1 , I 2.75HC1 1 1 6.251127, 109 7,10_(0H)2 l(cH2)3Naca2cH2oH ¦NHCH2CH2tJHCH2CH2O l100 l259 Cures l222, ~33 I I I }2.5 I!57 146 ' (OH)`2 ¦(cq2)3~;HcH2~H2o~l INacH2c:i2c~2Na2 l100 ¦135, lSS
0.1HC1 1 1 50 l160, 146 ( ~3)2 ¦ca2CH2~Hc~2cH2OH ~aCH2CH2NHCH3 1 12.5 l277, 275 Cures ¦ CH3C2#-HB~ ¦ ¦ 6.25¦277, 275 Cures I I 1 3.121263, 177 Cures 7,10-lOH)2 jCa~cH2~H2 INHCH2CH2tiHCH2CH2NMe2 ¦ 50 !220 Cures i 3.3HC1 1 1 25 1192, 177 i j 1 12.5 il86, 157 7,10-(OH~2 ¦C~2cH2aH2 ¦ 2 2 2 2C 2 ¦ 6.25l184, 194 2.1~C1 1 1 3.12l177 194 ~ 1.56jl81 172 ?,10-(CH)2 ¦C.H2CH2CH2NH2 IN~CH2CH2#HCU.2CH20H ¦ ;0 l235 Cures j 2HCl I I i2.5 l247, 163 Cures I I 1 6.25l193, 134 7,10-(OH~2 tC!~2CH2CH2~H2 ¦NHCH2CH2NHCH2CH2NMe2 ¦ 25 122a, 130 I 3HC1 1 1 12.5 1219, 123 7,10-(OH~2 ¦CH2CH2NHCH3 ¦NHCH2CH2HCH2CH2OH I 12.5 ¦147 1 2HCl I
7-OH ICH2CH2NqCH2CH20H ¦NHCH2CH2NHCH2CH2OH ¦ 25 l285, la4 Cures 2HC1 1 1 12.5 l22a, 142 Cures ~j Ij j 6.25j133, 134 10-OH ICH2c~2NHcH2cH2H INHCH2cH2NHcH2cH2 ¦100 1221, 184 I 2,1HC1 1 1 50 l172, 162 i j 1 25 j163, lSS
7~a~lo-(oH)3~cH2cH2NHcQzcH2oc ¦NHCH2CH2NHCH2CH2OH I 25 ¦265 Cure3 I 2.lHC1 1 1 12,5 l257 Cure~
7~9~1o-(oH)3icH2cq2`lHcH2cH2oH INHCH2cH2NHcH2cH2H ¦ 3.12¦165 I 2.1HCl i 1 1.561155 . CLG-l -65-~0~ ol ,., D~r _~

1.1 Q Lg 5~ 00 OU~ CI O _ C l ~_U C __ _____ _ ___ O ~ 2~j=o , O '' o I I o o!l x~x o~ - ___________ o o o _ _ "~ ¦ U _ ~

,. ~ L~2 Ci.G-l -66-~[Z-lDiethvl-a:nlno?sChv' 1-7~10-d~h~droxv-5-~ (2-hvdrcxvfJthvl)-z:n~nole~hvllamlno~anthra[l,9-cdlpvrzzol-6(2!1)-on2 Dlhvdrochlo~ide in Yice 1~0 N--~ (CHz) 2N (Et~ 2 $~ ~ 2HCl OH O Nff(CH2)2NH~CH2)20H

I Route i --I'umor Frumor/la9ginenl ~ Do,5e ~ C x 1001 ~ Tumor __ I Drua ¦ mg/ g) I ~Pe~cent) IRedUction ~DJ-PC6 Plas~acytoma IIP/}P l004DXO3l 16 1 163 I I I ~ 1 216 316 :~slanoma (35Fl)IrP~rP ¦QO1DXO9I 8 1 176 ~ 1 151 (36t3~, 1 )anoma I IP/IP I QOlDxO9 1 6 1 189 Colon 18 (aDPl) 15.~IP IQOlOx09¦ 16 1 l 7.l LJ.210 Lsukzr~la(CDFl)lIP~I2 IQOlDXO9l 16 1 133 l 1 137 ~5076 Ovary IrP~IP IQ040x041 lO I 260 I I 1 1.251 143 167 (1930~ al~d re~erenceC-ajnCitr ~Clhem0th9rlpy Reviews~ 7, ~l~53l~

CL~ 67-In addi ion ~o ~heir usef~!lness as anti~iotic and anti~ur.gal aqen~s and as antileukemic agent.s~ cer_ain of the comDounds of t~e invention display in Yit'o activi~y agair.st solid tumors when tested by the ~ollo~.~ing proc~dure, ~ CT~ (human colon adenocarcinoma) cells ar~
t.ypsinized using Trypsin-EDTA0 ~ single cell susDension is ~chieved by DasSinq the cells throuqh a 25 ~ug~ needle with a 20 cc syringe~ ~ cell suspension is ?r~p~red using RP~I 164~ srow;h ~edi~m ~avail~ble ~roln Gibco Laboratories) + 10~ f~t~l.calf ser~m ~ 50 ug/ml g~ramyci;~ wi:h a c~ll concentra~ion of approximately 30,000 cells/mlO The cell sus~ensian is dispe~ed in Linbro 2~-well plates; 1 ml/we~l. T~e plates are incubated ~oc apnroxi~ately 48 hrs ~t 37C
in a 5~ C02 at~osohere. ~t t~is time tes~ compcunds are added in the ap~ropr1ate cancent~ation. Pive ~1 o~ the 2C0 ~g~ml stoc~ solution is added to eac~
well in a primary test~ Ten ~1 of the ap~ropriate dilution is added to each well or a titration .est.
The plates are reincubated ~n additional 60-6~ hrs a~
37~C in a 5~ C02 a~osphereO The test is read by Iysinq the cells usin~ a mix o~ cationic surfactan~, ~lacial ac~tic ~cid and sodium c~.loride. Two ml of the lysed cell sus~ension from each ~ell is added ~o

8 ml o~ diluen~. Each sample is re2d with~a Coulter counte~ ~Z8~ ~od~l). The ac'ivity o~ each sample is me~sured as a pe.cent~ge of the con~rols and the dat~
is repo~ted as I3so, ~hat i5 ~he molar quantity o~
drug required to kill 50~ of tne t~mor cells.
Utilizing ~his proc~dure, ~h~ follawing results ~ere obt~in~d .ar ~Ppresent~ e compour.ds o~ the inven~ion~

~5~

C~ 6a-In Vitro Activity o~ Amil~oanthra~yrazoles Against Hu~an Colon Aclenocarc;no~a U --N-Z
X~' O NRY

Xl Z9 I N~Ys ¦ IDso ~olar Hl~cH2)2NEt2 ¦ ~ 2)2NEt2 ~ x 10-7 1 ~2HCl l I
B¦ Ctl3 INH~cq2)2N~t2 1 4.1 X 10-7 ( 2)20H ¦ ( 2)2NEt2 ¦ 1.3 x 10-6 1 ~2HCl Y¦ H ¦N~(CH2)2Nff(CH2)20H¦ 1.5 x 10-6 j HCl H¦ CH3 ¦NH(CY2)2NH(CH2)20H¦ ~.0 X lo-7 I ffCl I I
a¦(CB2)2NEt2 1 ~ 2)2NH2 ~ 5.2 x 10-3 I 2qCl H¦ ~Cil2)2:~H~CH2)2oH ¦N!~cH~)2NH~c~q2)oH I 9.6 x 1o-7 'CH3C02H l l rs~

CLC-l -69--Xl 8 I NRY ¦ ILlB0 !Yolar H ¦ ( C QZ ) 2 YH ( CH 2 ) 2 OH ¦ NH ( CH Z ) 2 NH2 I ~ . 2 X 10 - 8 HI (CH2)2 H(ca2)2GH¦NH(CH2J2 2 I 1.2 X 10--7 8 ¦ ( C q z ) 2NH ( CH2 ) 2 0H ¦ N~ ( C~ 2 ) 2 ;M 2 1 2 . 3 ~ l Q -7 H¦ (CH2)2NH(Gl2)20HlNQcH3 ¦ 2.B X 10--7 ~ICl I I

2HCL ¦~lQ(cH213NEtz ¦ 4. a x L0-7 ¦ ~ Hi2 ) 2NEt2 ¦ 1 2 ) 2N ~ ¦ 1, 2 X 10-7 ~211Cl ¦ H(Ca2)3NEt2 1 1.8 X 10-7 HI ~C~2)2NE t2 ¦NHIcH2)~NEt2 I 2.2 x 10-7 2.qcl H¦(C~I2)2NEe2 1 ~ 2~7NEt2 I 2.2 X 10--6 2~iCl I I
1 2 ) 2 t2 ¦ ( 2 ) 2N~ NH I 3. 8 x 10-7 2HCl ¦NH(CH2)ZN~CH2~20Hl 6.a x 1o-8 t~
C~ 70-. .
:C I 2 I N~Y I IDs~ Mol~r 7 1-(Y)2i(-H2)2NEt2 ¦NH(CH2)2Na(C82)20KI 2.7 ~ 10-7 7 iO-(OH)ZI(CiI2)2NEt2 INH(C;2)2~Et2 1 6.~ X 10-7 ~ )2; ~a3 ¦N~(CHZ)2NH(CH2)20a¦ 7 9 X 10 7 7 lo - !oH)2t~cH2)2NEt2 ¦ ( 2)~ X2 1 3.8 X 10-7 I .2HC1 7 L0-(08)2~(CH2)2NEt2 INH'C~2'2NH~e I 1 2 ~ 10-7 7~1O-!OH) (CB ) NMe ¦NH(CH2)ZNHtCH2)20HI 1.a X !0-7 7 10-~OH)2¦ Ca2CH08CH2~E~2 INH(CH2)2 2 1 ~.6 X 10-7 7 10-~0~)2¦ CX2CHOHCX2NEt2 INH~CH2)2WH(CH2)20 1 I .2~1C1 7~10-~OH)2~(CH2)20H INH~C8Z)2NMe2 1 1.7 X 10-7 I .~C1 I ZHC1 1 ( 2)2NH2 1 1.~ X 10-7 7 1a t~l)21~CI2)2 12 ¦NH(CH2)2NHtCH2~20HI 1.7 ~ 10-6 -r NRY I IDso Molat-7,10-(OH)2t (C~2)2NH(Ci2 )2q j ~NJi C-~3 j ;,4 x 10-7 ~ 2HCl 7~1o-(oH!2i(c.!2)2~H2 ¦ ! zl2N;i2 j 3.1 x 10-7 ~ 2HCl 7,10-(OH)2; (-H2)2iiMe2 ¦ NH(CH2)3NH2 ¦ i.l .Y 10-6 ~211Cl 7,10-(OH)2~ i2)3~Me2 j NH(Ci2)3NH2 j 3.5 x 10-7 - 2HCl 7~lo-(o!i)2lcH2cH2cH2NM~2 iN~C~q2cH2`~iHcH2cH2o~i 1 9.2 x 1o-8 ~ 2HCl 7~lo-(oq)2ilc1l2cH2NMecH2cH2o~qiNHc~q2cH2NEcH2cH2o 1 . 8HCl 7~10--(oH12lc~q2cH2qHcH2cH2oH INHCH2C 2 3 ¦ '~' x 10-7 -3.3HCl ¦NHCH2CH2-qHCH2CH2NMe2¦ 1.2 x 10-6 .10--(OH~2~ 2cS12~jjl2 ~ l(CH2~3NHCH2C~q7H ¦ 2-8 ~ 10-7 2 lilCl l I
~ 2 9iiCi I 12CH2CH~NH2 ~ X 10~7 7~10-1os~2lcH2cs~cs~2~`~H2 ¦NHC112CS12NHCR2Cil20H I 7.7 x 10-7 7,1~i-(OH~2!CH2cH2NHcH3 ¦NHcH2cH2NHcH2cH2oH I 2.3 x 10-7 ¦CH2cH2NHcH2cH20H INHcH2cH2NHcH2cH2oH I 6-1 x 10-8 i ICS~2CH2r~HCH2CH20H INHc~q2cH2NHcH2cH2oH I 1.1 X lo-6 7-oH!cH2cH2NHcH2cH2oH jNHcH2cH2NHM0 1 2.7 x 10--8 ~l~8Hcl l I

., N--N-Z

NRY O

Z I NRY ¦ :tDso Molar _ _ , (CH2)2NEt2¦ N~(CH2)2~Et2 j 2~,2- x 10--7 ~ 2HC1 ¦ i ( CH2 ) 2NEt2 ¦ ~H ( C~2 ) 2NH ( C~2 ) 2OH I ~ . 3 x 1o--8 CTJG-l -73~
When being utilized as antibiotic and antifungal agents, the compounds of the invention can be prepared and ad.ministered in a wide variety o~ topical~ oral, and parenteral dosage forms. It will be clear to those skilled in the art that the 'ollowin~ dosage forms may comprise as the actlve component, either a compound of formula I, certain of the compounds of ormula II or a corresponding pharmaceutically acceptable salt of one o. said compounds or a mixture oE such compounds and/or salts.
For preparing phar.~aceutical compositions from the compounds described by this invention, inert, phar~aceutically acceptable carriers can be either solid or liquid Solid form preparations include powders, tablets, dispersible granules, capsules, cachets, and suppositories. A solid carrier can be one or more substances which may also act as diluents, flavor1ng agents, solubilizers, lubricants, suspending agents, binders, or tablet disintegrating agents; it can also be an encapsulating material. In powders, the carrier is a finely divided solid which is in admixture with the finely divided active compound. In the tablet the active compound is mixed with carrier having the necessary binding properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain fro~ 5 or 10 to about 70 percent of the activ.e ingredient. Suitable solid carriers are magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dex'rin, starch, gelatin, tragacanth, methyl cellulose, sodium carboxy~ethyl cellulose, a low melting wax, cocoa butter, and the like. The ter~
"preparation" is inten2ed to include the formulation of the active compound with encapsulating material as carrier providing a caQsule in which the active co~.ponent ~with or witAout other carriers) is CLG-l -74 surrounded by carrier 9 which is thus in association with it. Simllarly, cachets are incl~ded. Tablets, powders, cachets, and capsules can be used as solid dosage forms suitable for oral administration.
Liquid form preparations include solutions, suspensions, and emulsions. As an example ~ay be mentioned water or water-propylene glycol solutions for parenteral injection~ Liquid preparations can also be formulated in solution in aqueous polyethylene glycol solution. Aqueous solutions suitable for ora:L
use can be prepared by dissolving the acti-~e component in water and adding suitable colorants, Llavors, stabili2ing~ and thickening agents as desired.
Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, i.e., natural or synthetic gurns, resins, meth~l cellulose, sodium carbox~methyl cellulose, and other well-known suspending agents.
Topical preparations include dusting powders, creams, lotions, gels, and sprays. These various topical preparations may be formulated by well known procedures. See for example Remington's Pharmaceu-tical Sciences, Chapter 43, 14th ed. 1~70, Mack Publishing Co., Easton PennsylYania 18042, USA.
Pre~erably, the pharmaceutical preparation is in unit dosage form. In such form, the preparat~ion is subdivided into unit doses con~aining appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package con-taining discrete quantities of p-eparation, for example, pac~eted tablets, capsules, and powders in vials or ampoules. The unit dosage form can also be a capsule, cachet, or tablet itsel~ or it can be the appropriate number of any o these packaged form.

CLG-l -75-The quantity of active compound in a unit dose of preparation may be varied or adjusted from 50 mg to 500 mg according to the particular application and tne potenc~ of the active ingredient.
In tnerapeutic use as antibiotic and antifungal agen~s the compounds utilized in the pharmaceutical ~ethod of this invention are administered at the initial dosage of about 0.1 mg to about 50 mg per kilogram. A dose range of about 005 mg to about 10 mg per ~ilogram is preferred, The dosages, however, may ~e varied depending upon the requirements o~ the patient, the severity of the condition being treated, and the compound being e~ployed. Determi-nation of the proper dosage for a particular situation is sJithin the sklll o~ the ar~g Generally, treat~len~
is initia-ted with smaller dosages which are less than the optimum dose o~ the compound. Thereafter, the dos~ye is increased by small-increments until the !~
optimum ef~ect under the circumstances is reached.
For convenience, the total daily dosage may be divided and administered in portions during the day if desired.
The active compounds may also be administered p~renterally or intraperitoneally. Solutions of the active compound as a free base or pharmaceutically ~cceptable salt can be prepared in water sui~ably mixed with a surfactant such as hydrox~propyl-cellulose. Dispersions can also be prepared in glycerol, liquid polyethylene ~lycols, and mixture~
thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms.
The pharmaceutical forms suitable for injectable use include sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation oE sterile injectable solutions or dispersions. In all cases the form must be ste.ile and mus. be fluid ~2~

to the extent tnat easy syrinsability existsO ~t must be stable under the conditions of manufacture and storage and must be preserved agai.nst the contaminating action of miCrOQrganiSmS such as bacteria and fungi~ The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol ~for exa~ple, glycerol, propylene glycolf and liquid polyethylene glycol, and the like), suitable mixtures thereof and vegetable oilsO The proper fluidity can be maintained, for example, by the use of a coating such as lecithin 9 by the maintenance o~ the required particle size in the case of disper~
s ion and by the use of surfactants~ The prevention of the action of microorganisms can be brought: abou~ by arious antibacterial and antieungal agents, for example, parabens~ chlorobutanol, phenol, sorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents~ for example, sugars or sodium chloride~ Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gela~in.
Sterile in~ectable solutions are prepared ky incorporating the active compound in the required amount in the appropriate solvent with vario~s of ,he other ingredients enumeratecl above, as required, ollowed by filtered sterilizationO Generally~
dispersions are prepared by incorporating the various sterillzed active ingredient into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above~ In the case of the sterile powders for the preparation of sterile injectable solutions/ the preferred methods of preparation are vacuu~ drying and the free~e-drying technique which yield a powder of the active ingredient plus any additional desired CLG-l -77~
ingredient from a previously sterile-filtered solution .hereof.
As used herein, "phar~aceutically acceptable carrier" includes any and all solvents, dispersion media, coatings, antibacterial and antlfungal agent~, isotonic and absorption delaying agents and the like.
The use of such media and agents for pharmaceutlcally active subs~ances is wel1 known in the art. Except insofar as any conventional media or agen, is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated.
Supplementary active ingredients can also be incorporated into the compositions.
It is especially advantageous to formulata parenteral composi-tions in dosage unit ~orm ~or ease of administration and unlformity o~ dosage. Dosage unit form as used herein refers to physically discrete units suitable as unitary dosages or the mammalian subjects to be treated; each unit containing a predetermined quantity of active material calculated to produce the desired ther~peutic effect in association with the required pharmac2utical carrier. The specification for the novel dosage unit forms of the inventio~ are dictated by and directly dependent on (a) the unique characteristics of the active material and the particular therapeutic eEfect to be achieved, and (b) the limitation inheren~ in ~he art of compounding such an active material for the treatment of disease in livin~ subjects having a diseased condition in which bodily health is impaired as herein disclosed in detail.
The principal ac~ive in~redient is compounded for convenient and ef~ective administration in effective amounts with a suitable pharmaceutically-acceptable carrier in dosage unit form as hereirbGEore disclosed. A unit dosage form can, for example, CLG-l -78-contain the pri}lcipal active compound in amounts ranging from about 0.1 to 2bout 500 mg, with from about a.s to about 250 mg being preferred. ExDressed in proportions, the a~tive compound is generally present in from aboùt 0.1 to about 500 mg/ml of carrier~ In the case of compositions cGntalning supplementary active ingredients, the dosages are dete~mined by reference to the usual dose and the manner o administration of the said ingredients. T~.e daily parenteral doses for mammalian subjects to be treated ranges from 0.1 mg/kg to 100 mg/kg. The preferred daily dosage range is 0O3 mg/kg to 10 mg/kc;~
The following nonlimiting examples illustrate the inventors' preferred methods for preparing the compounds of the inven~ion~

CLG-l -79-2-[2-(Diet_ylamino)ethYl)]-5-[[2-(diethyl amino]a _ hra~l,9~cd]pyrazol-6(2H)-on2 A mixture of 1.2 g (3.4 mmol) of 5-chloro-2-[Z-(diethylamino)e-thyl]anthra[l,9 cd]pyrazol-6(2~)-one 1.0 g (8 mmol) of N,N-diethylethylenediamine~ about 1 mg of anhydrous cuprous chloride and 30 ml of anhydrous 2-ethoxyethanol is heated at reflux under argon. After seven hours, an additional 0.5 g (4 mmol) of the diamine and about 1 mg of catalys~ is added and the mixture is refluxed for 23 hours~
cooled, and concentratedO The residue is dissolved in dichlorome~hane, washed successively with wa.er, di.lute ammonium hYdroxide, and brineO Chromatography of the dried dichloromethane layer over silica gel with 10:1:89 methanol:triethylamine:dichloromethane provides the puri.~ied product Dissolution in hot 2-propanol followed by treatment with excess hydrogen chloride in 2-propanol a~fords 1.2 g of the dried product as a salt with 2.1 equivalents of hydrogen chloride solvated with 1.2 equivalents of water; mp 262-276C (decompo3ition)~
5-Chloro-2-~2-~diethylamino)ethyl]anthra[l,9-cd]-pyrazol-~(2~)-one is prepared as follows:
A mixture of 4.15 g (15 ~mol) of 1,4-dichloro-

9,10-anthracenedione [J. Amer. Chem. Soc. 48; 3198 (1926)] 2.~ g (20 mmol) of (~-diethylaminoethyl) ~drazine ~J. Med.. Chem , l, 493, (1964)~ and 35 ml o~ pyridine is hea~:ed at reflux for ten hours, cooled, and concentrated~ The residue is dissolved in dichloromethane and washed with water. Chromatography of the dried dichloromethane layer over silica gel with ethyl acetate and then 95:5 ethyl acetate:methanol affords 3.8 g of a solid whose crystal'ization from 2-propanol gives 2.9 g of pure material; mp 90-92C.

~5~

CLG--1 - 8 0 ~
Dissolution o~ 0, 89 g of the product in hot 2-propanol followed by treatment with excess hydrogen chloride in 2-propanol affords 0.9 g of the hydrochloride salt; mp 263-256C (decomposition).

2-[2-(Diethvlamino)ethyl)]-5-[[2-[(2-hydroxyethv~
--- _ amino]ethyl]amino]anthra[l,9-cd]pYra o]-6(2H)-. . . ~ _ _ one A mixture of 2.5 g (7.1 ~mol) of 5-chloro-2-[2-(diethylamino)ethyl]anthra[l,9-cd~pyrazol-6~2H)-one, 1 g (9 mmol) of 2-(2-aminoethylamino)ethanol and catalytic amounts of anhydrous cuprous chloride and potassium iodide in 25 ml of anhydrous 2-ethoxyethanol is heated at reflux under argon, Additional 0.5-1.0 g po~tions oE the amine and catalytic amounts of -the halide sa}ts are added after six and 12 hours~
respectively. After a total reflux time of 30 hours, the mixture is worked up as described for Example l, with purification on silica gel utilizing first

10:1:8~ and then 15:1:84 methanol:triethylamine:ethyl acetate. Following treatment with hydrogen chloride, ~here is obtained 1.1 g of the dried pro2uct as a salt with 2.0 equivalents of hydrogen chloride solvated with 2.4 equivalents of water; mp Z39-241C
(decomposition).

5-[(2-Aminoethyl)amino~-2-[2-(diethvlamino)ethyl]
anthra~l,9-cd]pvrazol-6(2H) one A mixture o~ 1.6 g (~.5 mmol) of 5-chloro-2-[2-(diethylamino)ethyl]anthra[l,9-cd]pyrazol-6(2H)-one, 2.5 ml of anhydrous ethylenediamine, and 25 ml of anhydrous pyridine is heated at reflux under argon for seven hours, cooled, diluted with toluene, and concentrated. The solid residue is dissolved in dichloromethane, washed with water, and then brine.
Chro~atography o~ the dried dichloromethane layer over silica gel with 1:9 ~ethanol:dichloromethane pro~ides .

~5~L~J~2 CLG l -81-0.8 g of 'he product. Dissolution in hot 2-propanol followed by treatment with excess hydro~en chloride in 2-propanol affords 1.0 ~ of dried procluc~ as a sait with 2.0 equivalents of hydrogen chloride solvated with 1.8 equivalents of water; mp 276-279C
(decomposition).
The following compounds are prepared as described in Example 3 from 5-chloro-2-[2-(diethylami.no)ethyl]-anthra[l,9-cdlpyrazol-6(2H)-one and the corresponding amine:

2-[2-(Diethyl2mir.o?ethyl]-[[2-(4-morpholi~ l?ethYl)]-amino]anthra[l,9-cd]pyrazol-6~2H)-one Reaction with 4-(2-aminoethyl)morpholine gives the product as a sal~ with 2.0 equivalents of hydrogen chloride solvated with 1.2 equivalents of water; mp 288-290C (decomposition).
~X~PLE 5 `
2-~2-(Diethylamino)~thyl]-5-[E3 (diethylamino~ro~oyl]-~ - --amino]znthra[1,9-cd]pyra201-6(2H)-one Reaction with N,N-diethyl-1,3-propanediamine ~ives the product as a salt with 2.0 equivalents of hydrogen chl~ride solvated with 0.2 e~u.ivalent of water; mp 270-272C (decomposition) EX~MPL~ 6 2-~2 (Dlethylamino)et yl]-5-[[7-(diethvlamino~hep-Yl]-amino]anthra[l,9-cd]~vrazol-6(2H)-one . . . _ ~ .
Reaction wlth ~,N-diethyl-1,7-heptanediamine gives the product as a salt with 2.0 equi.valents of hydrogen chloride solvated with 0.3 equivalent of water; mp 190-192C (decor~position)D
EXAMPL~ 7 5-~[4-(Die~.hylamlno)butyl]amino]-2-[2~ Av ~ o ethyl]anth~a[1,9-cd]~yrazol-6(2H)-one Reaction wlth N,N-diethyl 1,4-butanediamine gives the product as a salt with 2.0 equiv~lents o~ hyd;o~er.

CLG-l -82-chloride solvated with 0.7 equivalent or water;
mp 2~3-246C (decomposition).
EXAMPL~ 8 2-~2-(Diethyl2mino)ethyl]-5-(hexrrlamino)anthra~
cd]-pyrazo1-6(2H~-one Reaction with n-hexylamlne gives the product as a salt with 1.0 equivalent of hydrogen chloride solvated with 0.1 equivalent of water; mp 176-179C
(decomposition) ~ X~PLE 9 2-~2-~ kylam~no)ethyl~-5-[~2-(1-pi~razinvl)eth~rl]-a.~ino]anthra[l ! 9-cd3pyrazol-6(2H)-one Reaction with 4-(2-aminoethyl)-1-piperazin~
carbo~ylic acid, benzyl ester, then hydrolysis o~ the isolated intermediate with hot 48% hydrobromic acid in acetic acid gives the product as a salt with 3.3 equivalents oE hydroyen bromide solvated with 1.4 eauivalents of water and 0.1 equiv21ent o~-~cetic -~ -- -acid; mp 284-287C (decomposition).
4-(2-Aminoeihyl)-l-piperazine carboxylic acid, benzyl ester, is ~repared from 4-(2-aminoethyl~
pipera2ine by a procedure analosous to that described for the preparation of (2-aminoethyl)-methylcarbamic acid, benzyl ester, in US Patent 3,~31,268; lH NM~
(deuteriochloroform): ~ 2.78 (triplet), 5.08 (singlet), 7.30 (singlet)~

5~2-~iethyla~ino)ethvl~amino]-2-methvlanthra[l,9-~ , .. .. _ .
cd]pyra~ol-6(2H)-one A mixture of 1~88 g (7 mmol) of 5-chloro-2~
~ethylanthra[l,9-cd]pyra~ol-6(2H)-one [J. Chem. Soc., 1630 ~1952)], 1.2 g (10 mmol) of N,N-diethylethylene-diam ner 0.14 g of anhydrous ootassium fluoride, and 10 ml o dimethylsulfoxide is heated at reflux under arqon for four hours, cooledr diluted with water, and extracted with dichloromethane. The dichlo~omethane extract is washed twice with brine and then ~ith 5~
J

CLG-l -83-aqueous hydrochloric acid. The acid solution is washed with dichloromethane, made basic with sod um carbonate, and extracted with dichloromethane. The dried dichloromethane layer is clarified with charcoal, filtered, and concentrated to a residue.
The salt ~as ~ade as descri~ed in Example 3 to aford 1.1 g of the dried product, after thorough washing with ether, as a salt with 1.8 equivalents of hydrogen chloride solvated with 0.7 equivalent of ~ater;
mp 260-264C ~decomposition).

5-[~2-[(2-Hydroxyeth~)amino]ethyl]amino]-2-meth anthra[l,9-cd~pyrazol-6(2H)-one A mix-ture of 1.75 g ~6.5 mmol) of 5-chloro-2-methylanthra[l~9--cd~pyrazol-6(2~)-one, 6 ml ~59 ~mol) of 2-~2-aminoethylamino)ethanol, catalytic amounts o~
anhydro~s cuprous chloride and potassium iodide, and 25 ml of 2-methoxyethanol is heated at reflux under '!~, ','''__ argon for four-hours, cooled, a~d~concentrated. ~he residue is dissolved in dichloromethane, washed with water, and then with 5~ aqueous hydrochloric acld.
The acid solution is washed with dichloromethane, made basic~ and extracted into dichloromethane, Chromatography of the dried dichloromethane extract over silica gel with gradient elution employing 5-t5%
methanol in dichloromethane provides the purified product~ The salt was made as described in Example 3 to afford 0.69 g o~ the dried product as a salt with 1.0 equivalent o hydrogen chloride solvated with 0.1 equivalent of water; mp 270-272C ~decompcsition).

2-(2-Hydrox~et_y~)-5-[-[2-[(2-hxdroxyethvl)amino]
e-thyl}amlno]anthra[l,9-cd]pyrazol-6~2H)-one A mixture or 896 mg (3 mmol) of 5-chloro-2-(2-hydroxyethyl)anthra[l,9-cd]pyrazol-6~2H)-one, 3.1 ml (30 mmol) of 2-(2-aminoethylamino)ethanol, and 6 ml ol ~nhydrous pyridine is heated at r~flux under argon for ~5~

8.5 hours, cooled, and concentrated to leave a residue.
Trituration Erom ether:2-propanol leaves a gummy solid which upon furt'ner trituration from methanol-ether provides 851 mg of the product. Dissolution in chloroform followed by treatment with excess hydrogen chloride in 2-propanol affords 923 mg of the dried product as a salt with 1.6 equivalents of hydrogen chloride solvated with 0.5 equivalent of water; mp 267-272 C (decomposition).
5-Chloro-2-(2-hydroxyethyl~anthra~1,9-cd]pyrazol-6(2H)-one is prepared as follows:
A mixture of 5.54 g (20 mmol) of 1,4-dichloro-9,10-anthracenedione, 2.2 ml (33.3 mmol) of (2-hydroxyethyl)-hydrazine and 20 ml of dry pyridine is stirred at 60C for 32 hours and concentrated. A solid residue is triturated with ether and then crystallized from chloroform to give 3.58 g of product; mp 209-211 C. Processing of the mother liquor affords 0.21 g oE additional product; mp 208-210 C.

5-[~2-(Diethylamino)ethyl]amino~-2-(2 ~ yethyl)-anthra[l,9-cd]pyrazol-6(2H3-one _ Reaction of 896 mg (3 mmol) of 5-chloro-2-(2-hydroxyethyl)anthra[l,9-cd]pyrazol-6(2H)-one~ 4.2 ml (30 mmol) of N,~-diethylethylenediamine, and 6 ml of anhydrous pyridine as described in Example 12 gives 1.02 g of the dried product as a salt with 1.75 equivalents of hydrogen chloride solvated with 0.5 equivalent of water; mp 199-205 C
(decomposition).
The following compounds are prepared as described in Example 12 from 5-chloro-2-(2-hydroxyethyl)anthra[1,9-cd]-pyrazol-6(2H)-one and the corresponding amine:

CLG-l -85-EX~PLÆ 14 _-(2-Hv~ xye~hyl)-5-[[2 (4-morphol _vl)eth~yl]amino]-,9 cd~Dyrazol-6(2~)-one Reaction with 4-~2-aminoethyl)mol~pholine gives the product as a salt with 1.9 equivalents of hydrogen chloride solvated with 0.5 equivalent of water;
mp 260C (decomposition).

5-[~3-(DiethYlamino~Dro~vl]amino]-2-(2-hYdroxYethvl) anthra~l,9-cd~p~razol-6(?H)~one ~ eaction with N,N-diethyl-1-1,3-prop2nediamine gives the product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.5 equivalent of water; mp 201-21nC (decomposition)O

5-t[4-(Diethvlamino _uty~amino]-2-(2_hydroxyethyl) anthrat ~ cdl~y~zol-6(2H)-one Reaction with N/N-die~hyl-1,4--propa~ediamln~
gives the product as a salt with 1.9 equivalents of hydrogen chloride solvated with 1.0 equivalent of water; mp 155-185C (decomposition)O
EXAMPL~ 17 5-[~7-(Die~ la ino)he tyl]amino~-Z-~2~'v~rc~ve hv'~-a thra~l, ~
Reaction with N,N-diethyl-1,7-heptanediamine gives the product as a salt with 1.0 equivalent of ~drogen chloride; mp 206-208C (decomposition)~ -2-~2-f~ydroxvethyl)-5-[[2-(1-piperazinyl)ethvl~amino]-anthra[l,9-cd]pyrazol-6(2H)-one Reaction with 4-(2-ami~oethyl)-1-piperazine carboxylic acid, benzyl ester, then hydrolysis of the isolated intermediate with refluxing 48~ hydrobromic acid in acetic acia and salt formation gives the product as a salt with 2.0 e~uivalents o~ hydro~en chloride solvated with 0.5 equivalent of water;
mp 292-297~C (decomposition)~

~ 5~ .2 C~G-l 86-~XAMPLE 19 5~[[2-~(2-Hvdroxvethyl)amino]eth l]amino]anthra[l,9-~3~
A mlxture of 2.54 g ~10 ~mol) of 5-chloroanthra-~l,9-cd]pyrazol-~(2~)-one [J. Chem. Soc., 1630 (1952)], 10 ml (100 mmol) of 2-(2-aminoethylamino)-ethanol, and 25 ml o~ znhydrous pyridine is heated at reflux under argon for 24 hours~ cooled, and concentrated. The residue is triturated with 2~propanol to give a solid whose dissolution in methanol:dichloromethane followed by salt formation as described in Example 3 affords 1.5 g of the dried product as a salt with l.S equivalents of hydrogen chloride solvated with 0.6 equivalent o~ water;
mp 251-~54~C (decomposi~ion)O
EX~'IPLE 20 5-[[2-(Diethylamino)ethyl]amino]anthra[1,9-cd]-pYrazol-6(2H)-one A mixture of 1.6 g (6.3 ~mol) of 5-chloroanthra-~l,9-c_]pyrazol-6(2~1]-one, 3.5 g (30 mmol) of N,N-diethylethylenediamine, and 20 ml of anhydrous pyridine is heated at reflux for 20 hours, cooled, and concent-ated. The residue is dissolved in dichloromethane, washed with water, and then extracted with 1% aqueous hydrochloric acid. The acid solution is ~ashed with dichloromethane, then made basic with aqueous sodium hydroxide. The aqueous solution is ex~ract2d with dichlorometharIe and ~he dried dichloromethane layer is concentrated to a residue w~Iich is converted into a salt as described for Example 3 to give 0.7 g of the dried product as a salt with 1.4 equivalents OL hydrogen chloride solvated with 0.1 equivalent of water; mp 120-130C.

CLG-l -87~

2-[2-~(2-Hvdro.Y ethYl)aminoleth 1]-5-[_[2-[~2-nydroxy-.Y ~
ethy~)amlno]ethyl~amino~anthra[l~9-cd]p~razol-6(2H) o A mixture of 1.91 g (5 mmol~ of 5-chloro-2~[2-~(2-hydroxyethyl)amino]ethyl]anthrall,9-cd]pyrazol-6(2H~-one, hydrochloride, 2.6 ml of 2-(2-aminoethyl-amino)etnanol, and 5 ml of anhydrous pyridine is heated at reflux under argon for 6.5 hours, cooled, and concentrated. Trituration of the solid residue with cold 2-propanol gives 1.43 g of the dried product; mp 154-156C. Crystallization ~rom slacial acetic acid: 2-propanol gives 1.35 g of the dried product as a salt wi-th :l.0 equivalent o~ acetic acid solva~ed with 0.5 equi~ralent o water; mp 146-148C.
5-chloro-2-~2-~(2-hydroxyethyl)amino]ethyl]
anthra[l,9-cd]pyrazol-6(2H)-one is prepared aS
Eollows:
To a refluxin~ mixture of 832 mg (3 mmol) of 1,4-dichloro-9,10-anthracenedione in 8 ml of dry acetoni-trile is added dropwise over 40 minutes, 4;0 my (3.8 mmol) of 2- r (hydrazinoethyl)2mino]ethanol in 3 ml of ace~oni~rlle, The mixture i5 refluxed for one ~our, cooled, and triturated with cold 2-propanol to give 602 mg of product; mp 140-142~C. Processing of the mother liquor affords 71 mg of additional product;
mp 124-126C. Cry~tallizatioll of the free base from glacial acetic acid gives the.diacetate sal-t; mp 125-130C~ The hydrochloride salt is prepared as descri~ed in Example 3; mp 260-263C ~decomposition).

3l~5~
, .
CLG-l -88-2-~ydrazinoethyl)amino]ethanol is prepared as ,ollows:
A solution of 86.8 g (1.0 mol) of N-(2-hydro~y-ethyl)ethyleneimine and 400 ml (about 6 mol) of 54 aqueous hydrazine is heated at reflux for two davs.
Excess water and hydrazine is distilled at 40-50C/13 mm, then the pot residue is distilled at 142C/0.10 mm to yield 80.9 g of product with an 88% purity. Care ful redistillation of a small sample gives analytically pure material; bp 120C~0.035 ~m.

5-~(2-Aminoet-h-yl)amin-o]-2-l2-[~2-hydroxyethyl?amin ethyl~anthra~l,9-cd]py-razol-6(~H)-o-ne Reaction of 1.91 g of 5-chloro-2-[2-~(2-hydroxy-etnyl)amino~ethyl]an~hra[l,9-cd3pyra~ol-6(2H)-one hydrochloride with 1.6 ml ~25 mmol) of 1,2-ethylene-di.amine, as described in Example 21, followed by concentration aEfords a solid which is washed with ether, 2-propanol, and a little dichloromethane, then triturated with methanol to remove a solid impurity.
The concentrated filt-ate is dissolved in water and purlfied over a column of HP-20 resin eluting first with water and then ~7ith methanol. Coricentration of the methanol eluate followed by salt formation as described in Example 3 affords 1.0 g of the dried product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.9 equivalent of water;
mo 263-2G7C (decomposition) 7 C~G-l 89-ethyl)amino]ethy~anthra [l,9-cd~pyrazo1-6(2H)-o Reac-tion oE 1.91 g of 5-chloro-2-~2-t(2-hydroxy-ethyl)amino]ethyl]anthra[l,9-cd]pyrazol-6(2H)-one, hydrochloride, with 3.5 ml (25 mmol) of. N,N-diethyl-ethYlenediamine as described in Example 21 affords 1.~ g of product; mp 132-133O Processing of the mo~her liquor affords 0.3 g of additional product;
mp 130-131C. Salt formation as described for Example 3 gives 1.6 g of the dried product as a sal~ wi.h 2.0 equivalents of hydrogen chloride solvated wi~h 1.0 equivalent of water; mp 272-274C (decomposition)O
EX~PLE 2~
5-[~2-Hydroxyethyl)amino~-2- E 2- [ ( 2-hy~droxvethYl ) -amino~ethvl]anthra[l,9-cd~pyrazol-6(2H)-one A mixt~re of 2.5 g (6.6 mmol) of 5-chloro-2-[2--1(2-hydroxyethyl)amino]ethyl]anthra~1,9-cd]pyrazol-6(2H)one, hydrochloride~ 2 ml (33 mmol) of 2-amino-ethanol and 13 ml of anhydrous pyridine is reacted and worl~ced up as described in Example 21 to afford a solid precipitate whose sal~ formation as described in ~xample 3 affords 1.4 g of the dried product as a salt with 1.1 equivalents o~ hydrogen chloride solvated with 0.6 equivalent of water, mp 260-261C
(decomposition)O
EX~MPL~ 25 2~2-l(2-~ydroxye~hyl)amino]ethyl]-5 ~ -- .
amino)ethvl]amino]anthra[l,9-cd]pxrazol-6(2H)-one Reaction of 2.72 g (7 mmol) o. 5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]anthra[l,9-cd]pyrazol 6(2H) one, hydrochloride, 1.2 g (14 mmol) of N,N-dimethyl-ethylenediamine, and 20 ml of pyridine for 42 hours at ~s~

CLG-l -90-reflux followed by workup as described in Example 21 gives a solid residue whose dissolution in hot methanol follo~ed by salt formation as described ln Example 3 gives 1.0 g of the dried product as a salt with 2~1 equivalents of hydrogen chloride solvated with 0~9 equivalent of water; mp 286-Z88C
(decomposition).

2-[2-[(2-Hydroxy-ethyl)amino~ethyl]-s-(methylamino) anthra[l,9-cdJ~yrazol-6(2H)-one Reaction of 5-chloro-2-f2-r(2-hydroxyethyl)--amino]ethyl]anthra[l,9-cd]pyrazol-6-(2~)-one~ hydro-chloride, with excess methylamine as described in Example 21 gives the p.oduct as a salt with 1.0 equivalent of hydrogen chloride, mp 285-288C
(decomposition).
EXA.~PLE 27 2-(2-Aminoethyl)-5-[[2-[(2-hydroxyethyl)amino]ethyl]
amino]anthra[l,9-cd]~yrazol-6~2H)-one A mixture of 3.0 g (8.9 mmol) of 2-(2-amino-ethyl)-5-chloroanthra[l,9-cd]pyrazol-6(2H)-one, 2.0 ml of 2-(2-aminoethylamino)ethanol, and 15 .~1 of anhydrous pyridine is heated at reflux ~or 30 hours, cooled, and filtered. The filtrate is concentrated and chromatographed over silica gel with 9~:2-1 dichloromethane: methanol:triethylamine7 then gradient elution ~o 99:2001 to provide the purified pr~du~t~
~al~ ~orma~ion as described in ~xa~ple 3 ~ives 0.8 g oE the dried product as a salt ~ith 1.7 equivalents of hydrogen chloride solvated with 1.0 equivalent of water and 0.2 equivalent of 2-propanol; mp 270-272C
~decom~osition).

CLG-l -91~
2-(2-Aminoethyl)-5-chloroanthra[l,9-Cd]pyrazol-6-~2H)-one is prepared as Eollowso To a solution of ~.0 g (3~6 ~mole) of lt4-di-chloro-9,10-anthracenedione in 10 ml of pyridine at 35 is addecl dropwise 1,9 ml of S2-aminoethyl)-hydraæine [~ritish Patent 880,332~. The mixture is stirred for four hours, concentrated, and purified on silica gel utilizing 94:5:1 dichloromethane~
methanol:triethylamineO Salt formaki Otl as described in Example 3 gives 0~45 g of the produc:t as a salt with 1.0 equivalent of hydrog~n cbloride solvated with 1.2 equivalenks of water and 0.1 equivalent of 2-propanol; T~ 28~1-285C ~decomposition).

2-~2-(Diethylamino)eth~1~-7,10-dihydroxy-5 [[2~(2 nydroxyethyl)amino]ethYl]amino]anthra~ 9-cd]
Pyrazol-6~2H)-one -Reaction of a mixture of 2.9 g (7.S mmol) o 5-chloro-2-[2-(diethylamino)ethyll-7,10-dihydroxy~
anthra[l,9-cd]pyrazol-6(2H)-one, 7.5 ml (75 mmol) of 2-~2-aminoethylamino)ethanol, and 35 ml of pyridine Eor four hours at reflux followed by workup as described in Example 21 and salt forma~ion as described in ~xample 3 gives 2.8 g of the dried product as a salk with 2.0 equivalents of hydrogen chloride solvated with 0.7 equivalent of water;
mp 198-202aC ~decomposi~ion).
5-Chloro-2-~2-(d.iethylamino)ethyl~-7~10-di-hydrox~anthra~1,9-cd]pyrazol-6(2H)-one is prepared as ~ollows:
Reaction of a mix~ure of 12.7 g (41 mmol) of 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione, 1~ 9 590 m~ol) of (~-diekhylamino~thyl)hydrazine, and 65 ml o pyridine at 50C for four hours followed by workup ~l~5~ 2 CLG-l -92-as described in Example 22 gives a residue that is dissolved in dichloromethane~ Chromatography over silica gel wi~h dichloromethane and then with 3~
methanol in dichloromethane affords crude material whose crystallization from 2-propanol gives ~.5 g of a purified solid; mp 136-140C. Salt formation as descri~ed in Example 3 on lo 5 g of this material gives 1.3 g of a dried solid as a saLt with 1.0 equivalent of hydrogen chloride solva~ed with 0.3 equivalent of water; mp 280-282C (decomposition)O
EX~PLE 29 2-[2-(Diethylamino)ethvl]-5~[[2-(diethylamino)ethyl]-amino~-7,10-dlhydroxy~nthra[l~9-cd]~yrazol-6~2~) on2 Reactivn of a mlxture oE lo 93 g (5 mmol) 0~ 5~
chloro-2-[2-tdiethylamino)ethyl]-7,10-dihydroxyanthra-[1,9-cd]pyrazol-6(2~ one, 2.9 g (24 mmol) of N,N-diethylethylenediamine; and 25 ml oE pyridine ~or five ~~ ~
hours at reflux followed by workup as described-i~
Example ?l gives a crude solid which is dissolved in dichlorome~hane. Chromatography over silica gel with 3~, 6%, and 10~ solutions of methanol in dichloromethane affords 1.6 g of pure material. Salt formation as described in Example 3 gives 1.4 g of the dried product as a salt wi~h 2.0 equivalents of hydrogen chloride solvated wi~h 0.3 equivalent of water; mp 290-~92C (decomposition)O
E~MPL~ 30 5-~[2~Aminoeth~l)amino]-2-[2-(diet~x~lamino)ethyl]-7~10-dihydroxyanthra[l,9-cd]p~razo1-6(2~)-one Reaction of 5-chloro-2-[2-(diethyla~ino)ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one with ethylenediamine as described in Example 28 gives the product as a salt with 2.0 equivalents of hydrogen chloride solvated ~ith 1.7 equivalents of water and 0.1 equivalent of 2-propanol; mp 277-281C
(decomposition).

CLG~ 93-2-[2-(Die~h~lamino)ethyl]-7,10-dihy~_ Y~r-5-[[2-(methylamino)ethyl~amino]anthra~l,g-cd3pyr~201-6(2H)-one ~ _ .
Reaction of 5~chloro-2-[2-(diethylamino)ethyl~-7,10-dihydroxyan~hra[l,9-cd]pyrazol-6(2H)-one with ~2-aminoethyl)-methylcarbamic acid, benzyl ester [US Patent 3,931,268] followed bv isolation of the intermediate as described in Example 29 then hydrolysis with hot 48~ hydrobromic acid in acetic ~cid glves the product as a salt with 2.3 equivalents of hydrogen bromide solvated ~ith 2.7 equivalents of water, mp 217-220C (decomposition).

2-~2-tDimeth~lamino)ethyl]-7,10-dihydroxy-5-~[2 [(2-hydroxyethyl)amino]ethyllamino]anthra[l,9-cd]pyraæol-6(2H)-one Reaction o 2~0 g ~5.6 mmol) oE 5-chloro-2-[2-(dimethylamino)ethyl]-7,10-dihydroxyanthra-1,9-cd]- -pyrazol-~(2~)-one, 5.6 ml of 2-(2-aminoethylamino)-ethanol, and 20 ml of pyridine at 70C for 24 hours followed by workup as described in Example 21 and salt f~rmation as described ill ~xample 3 gives 2~4 ~ of tha dried product as a salt with 2.4 equivalents of hydrogen chloride solvated with 2.0 equivalents of water; mp 310-313C (decomposition).
5-Chloro-2-~2-(dimethylamino)ethyl3-7,10-dinydroxyanthra[l,9-cdlpyrazol-6~2H)-one is prepared as ~ollows:
Reaction of a mixture of 15.5 g ~S0 mmol) of 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione, 10.3 9 (100 mmol) of (2-dimethylaminoethyl)-hydrazine ~J. Med. Chem., 1j493 (1964)] and 60 ml of pyridine at 35C overnight followed by ~orkup as described in Example 28 gi~es 3.8 g of product;
mp 1~3-146C. Salt formation as described in ~2~X~'~f~

CLG-l -94-Example 3 glves the product as a salt with 1.1 equivalents of hydrogen chlori2e solvated ~ith 1~2 equivalents of water; mp 295-300C
decomposition).
The following compounds are prepared as described in Exa~ple 32 from S-chloro-2-[2-(dimethylamino)-ethyl~-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one and the corresponding amine:
EX~MPLE 33 5-[(2-Arninoethyl)amino]-2-[2-dimeth~1am no)ethyl]-7,10-dihydroxyantnra[1,3-cd]pyra~ol-6(2H)-one ~ eaction with ethylenediamine gives the product as a salt with 1.3 equivalents of hydrogen chloride solvated with 2.4 equivalents of water; mp 300-302C
(decompo~lkiorl).

5-[(3-Aminoerop~Ll)amino]-2-~2-(dimethylamino)~thyl]
7,10-dihydroxyanthra[1,9-cd]pyrazol-6(2R)-one Reaction with 1,3--propanediamine gives the product as a salt with 1.9 equivalents of hydrogen chloride solvated with 1.4 equivalents of water; mp 281-28SC Idecomposition).

$-~[2-(Diethylamino)ethvl~2mino]-7,10-dihydroxv~-2-~2-hvdroxyethvl)anthra[l,9-cd]pyrazol-6(2H) one Reaction o a mixture o 3 3 g (10 mmol ) of S-chloro-7,1~-dihydroxy-2~(2~hydroxyethyl)anthra-[1,9-cd]pyrazol-6(2H)-one, 14;5 ml (100 ~nol) o N,N-diethylethylenediamine, and 2~ ml of pyridine for . 'hree hours at reflux followed by workup as described in Example 21 gives 2.47 g of a solid, mp 197-200C.
Salt formation as described in Example 12 affords 2.21 g o~ the dried product as a salt with 1.6 equivalents of hydrogen chloride solvated with 0.6 equivalent of water; mp 215-219C (decomposition).

f CLG-l -95-5-Chloro-7,10-dihydroxy-2-(2-hydroxyethyl)anthra-Il,9-cd]pyrazol-6(2H)-one is prepared as follows:
~ mix~ure of 12 g (40 ~mol) of 1,~-dichloro-5,8-dihydroxy-9,10-anthracenedione7 4~5 g (60 mmol) of (2-hydroxyethyl)hydrazine~ and 40 ml of pyridine i~
stirred at 50~ overnight, cooled, and oncentrated.
The residue is triturated successively with chloroform and hot ~e~hanol to give 1~1 g of the dried product;
~,p ~31-234C.
EX~MPLE 36 5- E [2-[(2-Hydroxyethyl)amino]ethylJa~ino]-7 dihydroxv-2-~2-hydroxyethyl)anthra[i~9-cd~pYra 6~2H)-one A mixture of 3.3 ~ (10 mmol) of 5-chloro-7~10~
dill~droxy-2~(2-hydroxyethyl)anthraLl,9-cd]pyrazol-6~2H)-one, 10.4 g (100 mmol) of 2-(2-aminoethylamino~-ethanol, and 20 ml oE pyridine is heated at reflux for fo~r hours, cooled, and concentrated. Successive tritura~ion of the residue with acetonitrile~
2-propanol, and methanol gives 1.35 g of a powder.
Salt ~ormation as described in Example 12 afords 1.06 g of the drled product as a salt with ].0 equi~7alent of hydrogen chloride sGlvated with 0.5 equivale~t of water; mp 195-203C (decompositlon).
The following compounds are prepared as described in Example 35 from 5-chloro-7,10-dih~droxy-2-(2-hydroxyethyl)anthra[l,~-cd]pyrazol-6~2H)-one and the correspondiny amlne.
EX~Pr.~ 37 5-~(2-Aminoethyl)amino]-7,10-dihydroxy-2-(2-hydroxy-ethyl)anthra[l,9-cd]pyrazol-6( H)-one Reaction WL th ethylenediamlne gives the product as a salt with 1.8 equivalents of hydrogen chloride solvated with 0.5 equivalent of water; mp '195~C
(decomposition).

C~ 96-EX~PLE 38 7,10-Dihydrox~-2-(2-hydroxvethyl)-5-[[2-(4-morpholinyl)ethyl]amino~anthra[l~9-cd]~
pyrazol-o(2~)-one -Reaction wi~h 4-12-aminoethyl)morpholine gives the product as a salt with 0.4 equivalent of hydrogen chloride and 0.3 equivalent of ~2ter; mp 240-251~C
(decomposition)~

5-[t2-~Dimethylamino)ethyl]2mino]-7,10-dih~droxy-2-(2-hydroxyethyl)anthra[l~9-cd]pyrazol-6(zH) o Reaction with N,N-dimethylethylenediamir.e gives the product as a salt wit~ 1.5 equivalents of hydrogen chloride ~olvated wi.~h 2.0 e~uivalents of water;
mp 250~C ~decornposition)~

5-[~2-AminoethYl)amino]-7,10-dihydroxy-2-methyl~
anthra[l,9 cd]~vrazol-6~2H)-one -Reaction of a mixture of 3.2 g (10.6 mmol~ of 5-chloro-7,10 dihydroxy-2-methylanthra[1,9-cd]pyrazol-6(2H~-one, 5 ml (74 ~mol) of ethylenediamine, and 5S ~1 of pyridine for sevell hours at reflux followed by worXup as described in Example 21 gives a solid residue. Dissolution of -the solid in hot methanol and N,N-dimethylforman~ide followed by salt formation as described in Example 3 affords 1.5 g of the ~ried product as a salt ~.ith 1~0 equivalent of hydrogen ~hloride solvated ~ h 0.2 equivalent of water and Ool equivalent of ~,N~dimethylformamide; mp 323-326C
~decomposition).
5-Chloro-7,10-dihydroxy-2-methylanthra[l,g-cd]-pyrazol-~2~)-one is prepared as followso A mixture of 12.4 g (~0 mmol) of 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione, 2.7 ml (50 m~ol) of methylhydrazine, and Z50 ml of pyridine is heated at 3SC for seven hours, treated with an additional CLG-l -97-1 ml of methylhydrazine, heated for se~-en hours at 35C, and cooled. The solids are filtered and recrys~allized from N,N-dimethylformamide to give 8.85 g of the dried product as a salt with 0.1 equivalent of hydrogen chloride, mp 2a8-305C
(decomposition).
EXA~PLE 41 7,10-Dihy2roxv-5-[[2-[(2-hy~d oxyethyl)amino]ethv~l]-amino]-2-methylanthra[l,9-cd]pyrazol-6(2H)-one Reaction of a mixture of 3.25 g ~10.8 mmol) of 5-chloro-7,10-dihydroxy-2-methylanthra[1,9-cd]pyrazol~
6~2H)-one, 3 ml (30 mmol3 of 2-(2-aminoethylamino~-ethanol, and 50 ml oL pyridine for seven hours at reflux followed by wor~up as described in Example.21 and salt ormation as described in ~xample 3 gives 1.8 g o the dried product as a salt with 1..0 equivalent o~ hydrogen chloride solvated with 0.6 equivalen~ o~ water; mp-2ao-2340c (decomposition).~ :
EX~MPLE 42 5-[[2-(Diethylamino)ethyl]amino]-7,10-dihydroxy-2 methvlanthra[l,9-cd]pYrazol-6(2~)-one . ~
Reaction of a mixture of 2.0 g (6.7 mmol) of 5-chloro-7,10-dihydroxy-2-methylanthra[l,9-cd]pyrazol-6(2H)-one7 3.5 ml (20 mmol) of N,N-diethylethylene-diamine, and 45 ml of pyridine for seven hours at reflux followed by workup as described in Example 21 and salt formation as desc~ibed in Example 3~gives 1.7 g of ~he dried pro~uct as a salt with 1.5 equi~7alents of hyclrogen chlor.~de solvated with 0.8 equivalent of water; mp 298C (decomposition).
~XAMPLE 43 2-[3-5Diethyl2mino)-2-hydroxypropyl]-7,10-dihydroxy_ 5-[[2-~(2-hydroxyethyl)amino]ethyl]amino]_nthra-[l,9-cd]pyrazol-6(2H)-one Reaction o, a mixture of 1.3 g (3 mmol) of 5-chloro-2-[3-(diethylamino~-2-hydroxypropyl]-7,10-dihydroxyanthra[l~9-cd]pyrazol-6(2H)-one, 2.1 ml ~;~5~
CLG-l -98-(21 mmol) of 2-(2-aminoelhylamino)ethanol, and 10 ml oE pyridine a. reflux for six hours follo~ed by workup as described ~or Example 21 and salt formation as described in Example 3 gives the product as a salt with 2.2 equivalents of hydrogen chloride solvated with 2.8 equivalents of water and 0.2 equivalent of 2-propanol; mp 105-120C.
5-Chloro-2-[3-(diethylamino)-2-hydroxypropyl~-7,10-dihydroxyanthra[1,9-cd]pyrazol-6(2~)-one is prepared as follows:
A mixture of 6.2 9 (20 mmol) of 1,4-dichloro-5,8-dlhydroxy-9,10-anthracenedione, 9.7 g ~60 m~ol) of l-(diethylamino~-3-hydra~ino-2-propanol tGerman Patent 1,126,877) and 35 ml of pyridine is stirred at 40C
for one hour then at room temperature overnight~ The mixture i9 concentrated and purified on silica gel utilizing 97:2:1 dichloromethane methanol:
triethylamine to give 1.7 g o~ product. Salt formation as described in Example 3 gives 1.4 g of the product as a salt with 1.0 equivalent of hydrogen chloride solvated with 0.7 equivalent of water; mp 264-267C (decomposition)O

5-~2-(Diethylamino3ethyl3amino]-2-[3-(diethylamino)-2-hydroxyprooyl]-7,10-dlhydroxyanthra~ cd]?yrazol-6(2H)-one Reaction oE 5-chloro-2-[3-(diethylamino~-2-hydro:~ypropyl]-7~10-dihydro;~yant!lra~l,9-cd]pyrazolo 6(2H)-one with N,N-die~hylethylenediamine as deQcribed in Example 43 sives the product as a salt with 2.0 equivalents of hydrogen chloride solvated wi~h 1.9 equivalents of water; mp 253-255C (decomposition).
EXA~PLE 45 5-~2-A~inoethyl)amino]-2-~3-(diet~lamino)-2-h~droxy-prooyl]-7,10-dihYdr?~lanthr_[l,9-cd]pyrazol-6(2EI)-on2 Reaction of 5-chloro-2-[3-(diethylamino)-2-i hydroxypropyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-~5 CI,G-l -99~
6(2H)-one with ethylenediamine as described in Example 43 gives the product as a salt with 2.0 equivalents of hydrogen chloride solvated with 2.8 equivalents of water; mp 148-15~C.

2-[3-(D~e~hylamlnw~propyl]-7_,10-dihydroxv-5-[ E2-[(2-hydroxyethyl-)amino]ethyl]amino1anthra[lr9-cd]
pyrazol-6(2H)-one Reaction of a mixture of 2.5 g (6 mmol) of 5-chloro-~-[3-~dimethylamino)propyl~-7,10-d-hydroxy-anthra~l,9-cd]pyrazol-6(2H~-onel hydrochloride, 2.8 ml (28 mmol) of 2-(2-aminoethylamino)ethanol, and 20 ml of pyridine at reflux for 24 hours followed by workup as described for-Example 21 and salt formation as described in Example 3 gives the product as a salt with 2,0 equivalents of hydragen chloride solvated with 1 0 equivalent o~ water; mp 311C
decompositiorl ) O
5-Chloro-2-[3-(dimethylamino)propyl]-7,10-dihydroxyanthraLl,g-cd]pyrazol-6(2H) one is prepared as follows~
To a suspension of 30.9 g (100 mmol~ of 1,4 dichloro-5~8-dihydroxy-9,10-anthracenedione in 200 ml of pyridine at 37C is added dropwise 14 g (120 mmol) of (3-dimethylaminopropyl)hydrazine ~J. Med_. Chem., 1;493 (1964)]. The mixture is diluted with 50 ml N,N-dime~hylformamide9 stirred for ten hours, and concentrated. The r~sidue is distribute.3 bet~ean dichloromethane an~ 5% aqueous sodium bicarbonate.
Purification of the dried organic layer on silica gel utilizing 95.5:4:0.5 dichloromethane:methanol:
triethylamine giv~s 8 g of product. Salt formation as described in Example 3 gives 7.S g of tAe product as a salt with 0.8 equivalent of hydrogen chloride solvated with 0.1 equivalent of 2-propanol; mp 267-271~
(decomposition).
!

~. ~ `5 ~
CLG-l -100-5-[(3-AmLno~ropyl)amino]-2-[3-(dimethylamino)~r~yl]-7,10-dih~droxyanthra[l,9-cd]~xrazol-6(2H)-one Reac~ion of 5~chloro-2-[3~(dimethylamino)propyl]-7,10-dih~droxyanthra~l,9-cd~pyrazol-6(2H)-one, hydro-chloride~ ~ith 1~3-propanediamine as described in Example 4Ç girJes the product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0 5 equivalent of water; mp >300Co EXA.~PLE 48 7,l0-Dihydroxy-5-[[2-~(2-hydroxyethyl~amlno]ethyl]
amino-2-~2-(methylthio~ethyl)anthra~l,9 cd]-pyrazol-6(2H~-one Reaction of a mixtuLe of 0.66 g (3.6 mol) of 5-chloro-~-(2~thlomethylethyl)-7,10-dihydroxyanthra~
1,9 cd]pyrazol~6(2EI)-one~ 108 ml (1~ mmol) of ~-t2~aminoethylamino)ethanol, and 16 ml of pyridine at reflux overnight followed by ~orkup as described ln Example 21 and salt ~ormation as.described in .
Example 3 gives 0.7 g of the dried product as a salt with 1.6 equivalents of hydrogen chloride solvated with 0.5 equivalent of water; mp >133C
(decomposition).
5-Chloro-2-(2-thiomethylethyl)-7,10-dihydroxy-ankhra-[l,9-cd]pyrazol-6(2H)-one is prepared ~s follows:
~ n ice-cold mixture of 2,64 g (5 mmol) of 5~chloro-2-(2-thiome~hyleth~ 7,10-bis(phenyl~
methoxy)anthra[l,9-cd]pyrazol-6~2H)~one in 15 ml dichloromethane is treated drop~ise during 30 minutes with 30 ml of a 1 M solution of boron trichloride in dichloromethane. The mixture is stirred for one hour then treated carefully with 30 ml of methanol. The mi~ture is wa med to roo~ temperature overn-ght then concentrated to a residue which is triturated with 2-proDanol to give a red solid. Fur~her trituration '~ , ~s~

CLG-l -101-with 75 ml of boiling methanol gives 0.9 g of pure product; rnp 186-190C~
S-Chloro-2-(2-thiomethylethyl)-?,10-bis(phenyl-methoxy)anthra[l,9-cd]pyrazol-6(2~)-one is prepared as ~ollo~s:
A mixture of 5.1 g (10 mmol) of 5-chloro-2-~2-hydroxyethyl)-7,10-~is(phenylmethoxy)anthra-Il,9-cd]pyrazol-6(2~)-one, 9.4 g (100 mmol) of methyl-disulfide, 20.2 g (100 mmol) of tri-n-butylphosphine, and 50 ml of N,N-dimethylformamide is stirred over-night at roo~ temperature. The mixture is cooled and treated carefully with 7~ ml of water. The orange solid is collected and washed successively with water, 2-propanol, and diethyl ether to give 5.1 g of the dried product; mp 155-160C~
5-Chloro-2-(2-hydroxyethyl)-7,10-bis(phenyl-methoxy)anthra[l,9-cd]pyrazol-6(2H)-one is pre~ared as follows: -Reaction of a mixture of 35.4 g (72 mmol) of lr4~dichloro-5,8-bis(phenylmethoxy)-9,10-anthracenedione,

11.2 g (147 mmol) of (2-hydroxyethyl)hydrazine, 2.1 (37 ~ol) of anhydrous potassium fluoride, 7.4 9 (74 mmol) of ~nhydrous potassium bic~rbonate, and 220 ml of dry dimethylsulfoxide as described in Example 54 gives 33.1 g of the dried product;
mp 1?8-184C. Crystallization from chloroform raises the melting point to 201-204C~
1,4-~ichloro-5,8-bis(phenylmethoxy)-9,10-anthra-cenedione is prepared as ollows:
mixture of 51.3 g (160 mmol) of 1,4-dichloro-~,8-dihydroxy-9,10-anthracenedione (US Patent Numher 3,631,Q74), 46 g (330 mmol) of powdered anhydrous potassium carbonate, 44 ml (380 mmol) of benzyl bromide, and 670 ml of dry acetone are heated at re-flux for five days. The mixture is cooled, the solids are filtered, then ~ashed se~uentially with water, ) ~ ~ 5 ~ L~I~ 2 CLG-l -132-methanol, and diethyl ether to give 63.5 g of the dried pro2uct; mp 190-194C. Processing of the acetone filtrate gives 9.4 9 of a second crop; ~p 1~2-155C.
EXA~PLE 49 5-Chloro-2-[2-(diethylamino)ethyl]-7,10-dihydroxy=
anthra[l,9-cd~pyrazol-6(2H)=one An ice-cold mixture of 9.1 g (16 rnmol) of 5-chloro-2-~2-(diethylamino)ethyl]-7,10-bis(phenyl-methoxy)anthrall,9-cd]pyrazol-6(2H)-one in 30 ml of dichloromethane is treated dropwise during two hours with 96 ml of a 1 M solution of boron trichloride~
Following addition, the mixture is treated carefully with 30 ml of methanol. The mixture is warmed to room temperatuee overnight and the solid residue is collected, washed se~uentially with 2-propanol, methanol, and die~hyl ether to give S.5 g of the dried product as a salt with 1.0 equlvalent of hydrogen chloride, and solvated with 0.2 equivalent o~ water;
mp 280-282C (decomposition).
5-Chloro-2-~2-~diethylamino)ethyl]-7,10-bis-(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2~)-one is prepared a~ follo~s:
A mixture of 4.2 G ( 6.3 mmol) of ~-chloro-2-[2-~[(4-methylphenyl)sulfonyl]oxy]ethyl]-7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one, 4.~ y (60 ~mol) of diethylamine, 17 9 (12.6 mmol~ of powdered potassium carbonate, and 35 ml of dimethyl-sulfoxide is stirred overnighc at 50C. The mixture is cooled and diluted with 50 ml of water. The solid is collected and washed with water. The solid is crystallized from chloroform:2-propanol ~3:1) to give 2~1 ~ of product; mp 209-211C.
5-Chloro-2-[2-[[(4-methylphenyl)sulfonyl]oxy~-e~hyl~-7,10-bis(phenylmethoxy)anthra[1,9-cd]pyrazol-6(2H)one is prepared as follows:

z CLG-l -103-An ice-cold mixture of 22 g (43 mmol~ of 5-chloro-2-(2-hydroxyethyl)-7,10-bis(phenyl-- methoxy~anthra[l~9-cd]pyrazol-6(2H~-one, 1~ 3 g (65 mmol) of P-toluenesulfonyl chloride and 170 ml of pyridine is stirred Eor 50 hoursO The sclid i5 filtered, T~ashed with methanol and diethyl ether, and dried to give 10.5 y of the product; mp 203-206C
~decomposition). Processing of the fil'.rate gives 9.3 g of additional product; mp 182-188C
Idecomposition).
EX~MPLE 50 ~-~2-~2-~Dimethvlamino)e.h~l]amino~ethyl]-5-[~2-~(2-h~droxye~hyl)amino~ethyl~amino]-7,10-dihydroxyanthra-~1,9-cd]pvrazol~6(2H)-one Reaction o~ a mixture oE 3,6 ~ C7Og mmol~ 5-chloro-2-[2-~[2-(dime~hylamino)ethyl~amino]ethyl}-7,10-dihydroxyan~hra[l,9-cd]pyrazol-6(2H)-one, dihydrochloride, 4.5 ml (45 ~mol) of 2-(2-aminoethyl- ~- -amino)ethanol, and 35 ml o~ pyridine at 80C overnight ollowed by workup as described in Example 21 gives 0.5 g of product as a salt with 0.25 equivalent of hydrogen chloride and solvated with 0.75 equivalent of w~ter; mp 110 - 117Co ~ -Chloro-2-[2-[[2-(dimethylamino)ethyl]aminol-ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one is prepared as followsO
An i;ce-cold mixture of 9.3 g (16 mmol) of 5-chloro-~-12-[l2-(dimethylamino)ethyl]amino]ethyl]-7,10~bis-~phenylmethoxy)anthra~l,9~cdlpyrazol-6(2H)-one in 30 ml of dichloro~ethane is treated dropwise during tWQ hours with 96 ml of a 1 M solution of boron trichloride. Follo~ing addition, the mixture is treated carefully with 30 ml of methanol. The mixture is warmed to room tempera.ure overnight and the solid residue i5 collected, washed sequentially with 2-propanol, methanol, and dietnyl ether to give 3.68 g of the dried product as a salt with 1.8 ~5~
.

CLG-l -104-equivalents of hydrogen chloride and solvated with 0O2 equivalent of 2 propanol and 0~8 equivalent of water;
mp 260-268C (decomposition), S-Chloro-2-[2-[[2-~dimethylamino)ethyl]amino]~
ethyl]-7,10-bis(phenylmethoxy)anthra~l,9-cd]pyrazol-6(2H)-one is prepared as follows~
A mixture of 4.2 g (6.3 mmol) of 5-chloro-2-[2-[[(4-rnethylphenyl)sulfonyl]o:cy]ethyl]-7,'0-bistphenyl-methoxy)anthrall,9-cd]pyraol-6(2~)-one, 5.3 g ~0 m~ol) of N~N-dimethylethylenediaminef 17 g (12.6 mmol) of powdered potassium carbonate, and 35 ml of dimethylsulfoxide is stirred overnight at 50C.
q'he mixture is cooled and diluted with 50 ml of waterO
The solid is collected and washed with wat~r, The solid is heated in dichloromethane, the solution filtered, then concentrated~ Trituration of the residue with,hot ethyl acetate gives 1.7 g of the ' dried produc-t; t~ .1~8-153QC. . .

7,10-Dihydroxy-5-~-[2-[(2-hydro~yethyl-)amino]ethyl]
amino~-2-[2-[(2-h~droxyethyl)methylamino]ethyl]-an~hra~l,9-cd]pyrazol 6(2H)-one Reaction of a mixture of 3.3 g (7.3 mmol) of 5-chloro-7~10-dihydroxy-2 [2-[(2-hydroxyethyl)-methylamino~ethyl~anthra[l,9-cd]pyrazo1-6(2~)-one, hydrochloride, 3.6 ml (36 n~ol) of 2-(2-aminoethyl-amino)ethanol, and 30 ml of pyridine ovarnigh,t at 30C
~ollowed by wor~up as described ln Example 21 and salt forma~ion as described in Exa~ple 3 gives 1,~ g of ~he dried product as a salt wi.h 1.6 equivalents of hydrogen chloride solvated with 0.4 equivalent of water; mp 240C (decomposition)~
S-Chloro-7,10-dihydroxy-2-~2-[(2-hydroxyethyl)-methylamino]ethyl]anthra[l,9-cd3pyrazol-6(2H)-one is prepared as follows:

~S~ 2 CLG-l -105-~eaction of a mixture of 8.3 g (15 mmol) of `~ 5-chloro-2-[2-[(2-hydroxyethyl)methylamino]ethyl]~
7,10-bis(phenylmethoxy)anthra[l,9-cdjpyrazol-6(2El)-one, 87 ml of a 1 M solution of boron trichloride in dichlorome~hane, and 60 ml of dichloromethane as described for Example 49 gives 3.5 g of the dried product as a salt with 1.0 equivalent of hydrogen chloride solvated with 1.75 equlvalents of water;
mp 279-282C ld~composition) 5-Chloro-2-[2-~(2-hydroxyethyl)methylamino]
ethyl]-7,10-bis(phenylmethoxy~anthra[l,9-cd]pyra~ol-6(2H~-one is prepared as follows:
Reaction o~ a mixture of 1ODO g ~15 mmol) of S-chloro-2-[2-[[4-methylphenyl)sulfonyl]oxy]ethyll-/,10-bis(phenyl)methoxy)anthra[l t 9-cd]pyrazol-6(2H) one, 12.1 ml (150 mmol) of 2-methylaminoethanol, 4.1 g (30 mmol) of potassium carbonate, and ~0 ml of dimethylsulfoxide as described in Example 49 gives ~`
8.5 g of the product; mp 191-194~C.

7~10-Dihydroxy-5-[~2-[(2-hydroxyethyl)amino]ethyl]
amino]-2-[3-[(2-hydroxvethyl)amino]~ropyl]anthra-.

[l,~-cd]pvrazol-6(2H)~one Reaction of a mixture of 1.4 g (3.6 mmol) of 5-chloro-7,10-dihydroxy-2-[3-[(2-hydroxyethyl)zmino]-propyl]anthra[l,9-cd]pyraæol-6(2H)-one, hydrochloride, 3.7 ml (37 mmol) of 2-(2-aminoethylamino)e'ha~ol and 15 ml of pyridine overnight at 80C fol'ow?d by workup as described in Example 21 gives 0.9 g of the dried product solva'ed with 0.6 equivalent of water; mp 100-105C.
5-Chloro-7,10-dihydroxy-2-[3-[(2-hydroxyethyl)-amino]propyl]anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:

CL~ 106-Reaction of a mixture of 9.0 g (16 mmol~ of 5-chloro-2-[3-[(2-hydroxyethyl)amino]propyl]-7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6~2H~-one, 63 ml of a 1 M solution of boron trichloride in dichloromethane~ and 30 ml of dichloromethane as described for Example 49 gives 6.0 g of the dried produc~ as a salt with 0.8 equivalent of hydrogen chloride solvated with 0.7 equivalent of water;
mp 255-265C ~decomposition~0 5-Chloro-2-~3-[~2-hydroxyethyl)amino]propyl]7,10 bis(pnenylmethoxy)anthra~l,9-cd]pyrazol-6(2~-one is prepared as follows:
Reaction of a mixture of 13 4 g (13.7 mmol~ of 5-chloro~2-l3-[[4-methylphenyl~sulfonyl]oxy]propyl]-7,10-bis~phen~lmethoxy)anthra~1,9-cd]pyrazol~6(2H)-one, 12 ml (197 mmol) of 2 aminoethanol, 5.5 g ~39.4 ~nol) of potassium carbonate, and 120 ml of dimethylsulfoxlde as described in Example ~9^gi~-es ~ ~ -9~85 g of the product, mp 174-176C. Crystallization -from chlorofor~ gives material of mp 180-185Co 5-Chloro-2-~3 ~4-methylphenyl)sulfonyl]oxy]-propyl]-7,10-bis~phenylmethoxy)anthra[l,9-cd]pyrazol-6(2~)-one is prepared as follows:
Reaction of a mixture o 1301 g (25 mmol) of 5-chloro-2-~3-hydroxypropyl)-7,10-bis~phenylmethoxy)-an~hra[l,9-cd]pyrazol-6(2~)-one, 9 5 g (50 mmol3 of ~-toluenesul.onyl chloride, 9 ml ~5 mmol) of triet`nylamine r 150 mg 0~ ~-dimethylaminopyridine, and 125 ml of dichloromekhane at 5C for one day ~hen at room temperature for fi~e hours ~llowed by workup as described for Example 49 gives 14.3 g o ~he product;
mp 131-139C.
5-Chloro-2-(3-hydroxypropyl) 7,10-bis(phenyl-methoxy)anthra~l,9-cd]pyrazo1-6~2H)-one is prepared as follows:

CLG~ 107-A mixture of 48.9 g (100 mmol3 of 1,4-dichloro 5,8-bis(2henylmethoxy)-9,10 an~hracenedione, 18O0 g (200 mmol~ of (3-hydroxypropyl)hydrazine [J. Amer.
Chem~ Soc. 7~; 1283 (1954)~, 2.~ g (50 mmol) of _ atlhydrous potassium 1uoride~ 10~0 g (100 mmol) of anhydrous potassium bicarbonate, and 300 ml of dry dimethylsulfo~ide is stirred at 80C overnight. The warm mixture is diluted with 1.5 ml of water, then allowed to cool. The solids are collected by filtra-tion, washed sequentially with water, 2-propanol, and diethyl ether to a~ford 31.0 g of the dried product;
mp 159-163C. Processing of the filtrate gives 4.7 g of additional product; mp 150-154C~
EX~M.PLE 53 5-[(3-Aminopropvl~amino]-7,10-dih~droxy-2 [3-[(2-h~droxyethvl)amino]prop~l]anthra[l,9-cd]pyrazol-6t2H)-one Reaction of a mixture of 1.3 g (3.3 mmol) of 5-chloro-7,10-dihydroxy-2-l3-[(2-hydroxyethyl)aminoj-propyl]anthra[1,9-cd]pyrazo1-6(2H)-onel 2.9 ml (35 mmol) of 1,3 propanediamine, and 15 ml of pyridine at 80C o~ernigh~ followed by workup as described in Example 21 gives lo O g of the dried product as a salt with 0 1 equivalent of hydrogen chloride solvated with 0.3 equivalent of water and 0.1 equivalent of 2-propanol; mp 120-130C (decomposition).
E~AMPLE 54 7,10-Dih~droxy-2-~2-[(2-hydroxyeth~l)amino'ethyl]_ 5 [[2-[(2-hydroxyet~l)amino]ethyl]amino]anthr_[l,9-cd]-_ pyrazol-6(2H)-one Reaction of mixture of 1~28 g (3 mmol) 5-chloro-7,10-dihydroxy-2[2-[(2-hydroxyethyl~am~no~ethyl]-anthra~l,9-cd]pyrazol-6(2H)-o~e, hydrochloride, 1.5 ml (15 mmol) of 2-(2-aminoethylamino)ethanol and 6 ml of oyridine at 80C overnight followed by workup as described in Example 21 and salt formation as described in 2xample 3 gives 675 mg o the product as CLG-l -108-a salt with 2.0 equivalents of hydrogen chloride solvated wi~h 0.9 equivalent of water; mp 215-225C
~decomposition).
5-Cnloro-7,10-dihydroxy-2-[Z-~(2-hydroxyethyl~
a.~ino]ethyl]anthra{l,9-cd]pyrazol-6(2H~-one is prepared as follows:
To an ice-cold mixture of 26.8 y (48 mmol~ of 5-chloro-2-[2-[hydroxyethyl)amino]ethyl]-7,10-bis-(phenylmethoxy)an~hrall,9-cd]pyrazol-6~2~)-one and 60 ml of dry dichloromethane i~ added dropwise during 2 1/4 hours 794 ml o' a 1 M solution of boron trichloride. The mixture is stirred for an additional 0~5 hours t then 200 ml o' methanol is added dropwise during 1~5 hoursO The mixture is allowed to warm to rooln temperature oYernight and the solids are fil-tered, washed sequentially with methanol~
dichloromethane, dieth~l ether, and 2-propanol to give 14 7 g of the dried product; mp 175C (de~omposition);
Processing of the filtrate affords 5.'1 g of additional product; mp 125-135C (decomposition)O
Crystalli2ation of the solid from methanol gives a salt with 1.0 equivalent of hydrogen chloride solvated with 0.7 equivalent of water; mp 180-200C
(decompcsition).
5-Chloro-2-~2-[(2-hydroxyethyl)amino]e~hyl]-7~10-bistphenylmethoxy)anthra~l,9-cd]pyrazol-6(2H)-one is prepared a~ ~ollows A mi:cture of 58.~ g ~120 ~moL) of l~a-dichloro--5,8-bistphenylmethoxy)-9,10-anthracenedione~ 28.6 9 1240 n~ol) of 2-[(hydrazinoethyl)amino]ethanol, 3.5 g S60 m~ol) of anhydrous potassium fluoride, 12 g ~120 mmol~ oE anhydrous potassium bicarbonate~ and 360 ~1 of dry dimethylsulfoxide is stirred at 80C overnight.
The mixture is diluted with 400 ml of water and the oranse solids are filteredl washed sequentially wlth water, 2-propanol, and diethyl ether to give 51.2 g of the dried product; mp 164-1O8C.

CLG-l -109-The following compounds are prepared as described in Example 54 from 5-chloro-7,10-dihydroxy-2-[2-~(2-hydroxyethyl)amino]ethyl]anthra[l,9-cd]pyrazol-6(2H)-one nydrochloride and the corresponding amine:

5-~(2-Aminoethyl)amino]-7,10-dihydrox~-2-[2-[(2-hydroxyethyl)amino]ethvl]anthra[l,9-cd]pyrazol-6(2H)-one Reaction with ethylenediamine gives the prcduct as a salt with 2.0 equivalents o hydrogen chloride sol~7ated with 0.9 equivalent of water; mp 272-278C
(decomposition).
EX~MPL~ 56 5-[[2-(Dimethylamino)ethyl]amino]-7,10~dihvdrox~Y-~=[2-[(2-hydroxyethyl)amino]ethvl]anthr_ p~razol-6~2~)-one Reaction with N,N-dimethylethylenediamine gives the product as a salt with 1.9 equivalents of hydrogen chloride solvated with 1.7 equivalents o~ water;
mp 278-280C (decomposition~.

5-[[2-(Diethylamino)ethyl]amino]-7,10-dihydroxy-2-~2-~(2-hydroxyethyl)amino]eth~l]anthra[l~9-cd]pyra 6(2H ? -one React.ion with N,N-diethylethylenediamine gives the product as a salt with 1.9 equivalents o~ hydrogen chloride solvated with 1.5 equivalents of water;
m~ 228-231UC.
EX~M3?LF. 58 5-[~3-~minopropyl)amino]-7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl3anthra[1,9-cd3pyrazol-6-(2~)-one Reaction with 1,3-propanediamine gives the product as a salt with 1.7 equivalents of hy2rogen chloride sclvated with 1.0 equivalent of water;
mp 222C ~decomposition).
~, ~l~5~ 2 CLG-l -110-E~A~PLE 59 5-[(4-Aminobutyl)amino]-7~lo-dihydroxy-2-[2-l(2~hydr _thyl)amino]ethyl]anthra[ll9-cd]pyra~ol-5(2H)-one Reaction with 1,4-butanediamine gives the product as a salt with 1.0 equivalent of hydrogen chloride solvated wi~h 0.5 equi~Jalent of water; mp 2~0-245C
(decomposition).

5 r ( 5-A~inopentvl)amin?]-7,10-dihydroxy-2-l2-[(2-hydroxyethyl)amino]ethyl]anthra[l,9-cd]~yrazol-6(2H)-one Reaction with 1,5-pentanediamine gives the product as a salt with 1.9 equivalents of hydrogen chloride solvated with 0.7 equivalent of water;
mp 270-275C (decomposition), 7,10-Dihydroxy-2-f2-l(2-hydroxyethyl)aml_no]ethyl]-5-[[2-(4-mor~holinvl)ethyl]aminolant.'nra[1,9-cd]-pyrazol-6(2H)-one Reaction with 4-(2-aminoethyl)~.norpholine sives the product as a salt with 2.4 equivalen~s of hycrogen chloride solvated with O.B equivalent of water;
~,~ 2gOC (decomposi~ion).
EXAMPL~ 62 7,10-Dihydroxy-2-[2-f(2-hydroxyethyl)amino]ethyll-5-f_1~2-hYdroxyethyl)amino]oropyl]amlno]an~chra[l~9-cd]
pyra~ol-6(2H)-one Reaction with 2-(3-aminopropylamino)eth.anol gi~es the product as a salt wi.~h 2.1 equivalents of hydrogen chloride solvated with 0.8 equivalent of water and 0~1 e~uivalent of 2-propanol; mp 170-180C
(decomposition~.

~5~ 2 CLG~

5-[[2-[[2-(3imethylaminoet~xl]àminolethyl]amino]-7,1Q-dihydrox~L-2-[2-[~2-hydroxyethvl)amino]ethyl]anthra-[1,9-cd]pyrazol-~(2~)-one _. _ Reaction with N,M-dimethyldiethylelletriamine yives the prod~ct as a salt with 2.4 equivalents of hydrogen chloride solvated with 1.4 equivalents oE
water and 0.2 equivalent of 2-propanol; mp 80-90C
(decomposition)O
- EXAMPLE ~4 7,10-Dihydroxy-2-[2-[(2-hydroxyethyl)amino3ethyl]-5-(4-methyl~ iperazinyl)anthrall,9-cd3pyrazol-6~2~)-one Reaction with N methylpipera2ine gives the product a~ a saLt ~itll 202 e~ulvalsnts o~ hydroyen chloride solvatecl with 0.~ equivalent o~ water and 0.2 equivalen-t o~ 2-propanol; mp >123C (decon~position).
E'~AMPLE 65 5-[l2-(Dimethylamino)ethyl]methylamino]-7~lo-di-hydroxy-2-[2-[~2-hydroxyethyl) _ino3ethyl3anthra-[l,9-cd]-~yraæo1-6(2H)-one Reaction with N,N,N-trimethylethylenediamine gives the product as a salt with 2.1 equivalents of hydrogen chloride solvated with 1.9 equivalents of water and 0.2 equivalents oE 2-propanol; mp >91C
!decomQosition) ..
EX~MPI,E 66 5-~12-[(2-P~minoetllvl)amino]ethvl]amino]-7,10-di-hydro~y-2=~2-[(2-~droxyethyl)amino]ethYl]anthra-[1,9-cd]-pyrazol-6(2H)-one Reaction with diethylenetriamine gives the product as a salt with 1~0 equivalent of hydrogen chloride solvated with l.0 equivalent of water;
mp 210-215C (decomposition).

~ ~5~
CLG-l -112~

5-[[2-~3is(2-hydro~yethy~amino]ethyl]amino]-7 dihydroxy-2-[2-[(2-hydroxyethYl)amino]ethyl]anthra Reaction with N,M-bis(2~hydroxyeth~,1)ethylen~-diamine gives the product as a salt with 2.3 equiYa lents of hydrogen chloride solvated with 0.8 equivalent of ~ater; mp 230C (decompos:ition~, EX~PLE 6Q
5-~[3-[Bis(2-hydroxyethyl~amino]propyl]amino]-7,10-dihydroxy-2-~2-hydroxyethyl)ami~o]ethyl~anthra-[l,9-cd]pyrazol-6(2~-one R2action with N,N-bis (2-hydroxyethyl)-1,3-propanediamine gives the product as a salt with ~1 equi.valents o hydrogen chloride solvated with t).4 equivalent of water; mp lg8-215C (decomposition).

5-[[3-[[4-[(3-~minoprop~l)amino]butyl]amino]propy:l]- -amino]-7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]-ethyl]anthra[l,9-cd]pyrazol-6(2H)-one Reaction with spermine gives the product as a s~l~ with 2.75 equivalents of hydrogen chloride solvated with 0.6 equivalent of w~er and 0.1 equiva-lent o~ 2~propanol; mp 185~200C (decomposition)O
EX~MPLE 70 7,10-Dihydroxv-2-[2-[(2-hydroxyethyl)amino]eth~ 5-1[2-tmethylamin_)ethyl]amino3anthra[1, -cd]-pyra~ol-6(2E)-one Reaction wi~h (2~aminoethyl)-methylcarbamic a~id, benzyl ester followed by isolation o~ the intermediate then hydrolysis ~ith refluxing 48%
hydrobromic acid in acetic acid gives the product as a salt with 2.1 equivalents of hydrogen bromide solvated with 2.3 equivalents of water and 0.5 equivalent of acetic acid; mp 222~228C (decomposition).

~l~5~
CLG--l -113-EXAI~IPLE 71 2-(2-~minoeth~1)-7,10-dihydroxy-5-[[2-~(2-hydroxy-ethvl)amino]ethvl]amino]anthra[l,9-cd] Pyra 6~2H)-one Reaction of a mixture of 2.0 g (6 nunol~ of 2-~2-aminoethyl)-5-chloro-7,10-dihydroxyanthra [l,9-cd]pyrazol-6~2H)-one, 3 ml (30 T[rnol) of 2-(2-aminoethylamino)ethanol, and 25 ml of pyridine at reflux overnight follo~led by workup as described in Example 21 and salt formation as described in Example 3 gives 1.3 g of the product as a salt with 2.0 equivalents of hydrogen chloride solvated with O.5 equlvalent of water; IE~? 275-280C (decomposition~.
2-(2-Aminoe~hyl)-5-chloro-7,10-dihydroxyanthra-~l,9-cd]pyrazol -~(2~)-one is prepared Erom 2-(2-amino-ethyl)-S-chloro--7,10-bis(phenylmethoxy)anthra~1,9-cd~-pyrazol-6(2H)-one and boron trichloride as described in Example. 54 to give the product as a salt with -1.0 equivalent of hydrogen chloride solvated with 0.7 equivalent of ~iater; mp 265-268C (decomposition).
2-(~-Aminoethyl)-5-chloro-7,10 bis(phenyl-~nethox~)anthra[l,9-cd]pyrazol-6(2H)-one is prepared from 1,4-dichloro-5v8-bi;,(E~henylmethoxy)-9,lO-anthracenedione and (2-aminoethyl)hydrazine as described in ~xample 54 to give the product; mp 176-178C.
EXAI"lPLE 72 _inoeth~1)-5-[(2-aminoethyl)amino]- 7,10-dihydroxvanthra[1,9-cd]pvrazol-6(2H)-one Reaction of 2-~2-aminoethyl~-5-chloro-7,10--dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one with thylenediamine as described in Example 71 gives the product as a salt ~ith 1.9 equivalents of h~drogen chloride solvated with 1.0 equivalent of .~ater; mp >230C (decolnposition).

CLG-l -114-EX~.~PLE 73 2-(2-Aminoethvl)-5-[(3-aminopropyl)a~ino]-7,10-dlh~droxyanthra[l,9cd]pyr~zol-6(2H)-one Reaction of 2-(2-aminoethyl)-5-chloro-7,10-dihydroxyanthrall/9-cd]pyrazol-6(2H)-one with 1,3-propanediamine as described in Example 71 gives the product as a salt with 2.9 equivalents of hydrogen chloride solvated with 3.5 equivalents of water;
mp > 310C (decomposition~.

2-[2-Aminoethyl)-5-[~2-[[2-(dimethylamino)ethyl]-amino]ethyl]amino]-7,10-dihvdrox~anthra[l,9-cd]_-pyrazol-6(2~)-one Reaction of 2-(2 aminoe-thyl)--5-chloro-7,10-dihydroxyant'nra[l,9-cdlpyrazol-6~2H)-one with N,N-dimethyldiethylenetriamine as described in Example 71 gives th~ product as a salt with 3.3 e~uivalents o hydrogen chloride solvated with 1.0 equivalent of water and 0.2 equivalent of 2-propanol;
mp 245-260C (decomposition)O
EX~PLE 75 2--(2-Aminoethyl)-5-[[3-[(2-hYdroxyethyl)amino]oropyl}-aminol-7~10-dihydroxyanthra[l~9-cd]~yrazol-6(2H) one -Reaction of 2-(2-aminoethyl~-5-chloro-7,10~
dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one with 2-(3-aminopropylamino)ethanol as described in Example 71 gives ~he product as a ~alt with 2~ equival~nts o~
hydrogen chloride solvated with 1.0 equivalent of water and 0.2 eq~ivalent of 2-propanol; mp 175C
(decomposition).

7,10-Dihydrox~5-[[2-[(2-hydroxyethYl)amino]ethyl]-amino]-2-t2-methoxyethyl)anthra[lr9-cd]pyrazol-__ 6(2H)-one Reaction of a mixture o~ 2.0 9 (5.8 mmol) of 5-chloro-7,10-dihydroxy-2-(2-methoxyethyl)anthra-[l,9-cd]pyrazol-6(2H)-one, 5.8 ml (58 mmol) of 2-(2-aminoethylamino)ethanol, and 25 ml of pyridine at 85C overnight followed by wor~up as described in Example 21 gives 1.75 g of productO Salt formatîon as described in Example 3 gives 1.91 g of product as a salt with 1.1 e~uivalents of hydrogen chloride solvated with 0.3 equivalent of water and 0.2 equivalent o~ 2-propanol; mp 68-72C.
5-Chloro-7,10-dihydroxy-2-(2-methoxyethyl)anthra-~l,9-cd]pyrazol-6(2H)-one is prepared as follows:
Reaction of 11.9 g (23 mmol) of 5-chl`oro-2-~2-methoxyethyl)-7,10-bis(phenylmethoxy)anthra-[1,9-cd]pyrazol-6(2H)-one, 91 ml of a 1 M solltion of boron trichloride, and 46 ml of dry dichloromethane as descr.ibed in Example 24 givcs 6.25 g of the dried product; mp 137~145C (decomposition).
5-Chloro-2-(2-methoxyethyl)-7,10-bis(phenyl~
methoxy)~nthra[l,9-cd]pyrazol-6(2H)-one-is-prepared~a~
~ollo~s:
~ n ice-cold mixture of 3.2 g (6 mmol) of S-chloro-2-(2-hydroxyethyl)-7,10-bis(phenyl-methoxy)anthra[l,9-cd]pyrazol-6~2H)-one, 1.23 ml (20 mmol) of j.odomethane, and 20 ml ~ N,N-dimethyl-formamide is treated gradually with 0.18 g (8 mmol) of sodium hydride. The ice bath is removed and the mix~ure is stirred for two hours, treated with five drop~ of glacial acetic acid, then diluted with water.
The solids are filtered, washed sequentially with 2-propanol and die~.h~Il ether to give 20 8 g oE the dried product; mp 174-178Co 5~t(2-Ami.noe~hyl)amino~-7,10-dihydroxy-2-(2-methox~
ethyl)anthra[l,9-cd]pyrazol-6(2H~)-one Reaction of 5-chloro-7,10-dihydroxy-2-(2-methoxy-ethyl)anthra~l,9-cd]pyrazol-6(~H!-one with ethylel~e-diamine as described in Example 76 gives the produc' ~.5~
CLG-l -116 as a salt with 1.0 equivalent of hydrogen chloride solva~ed with 0.3 equivalent of water, mp 263-268C
(decomposition~
EX~MPLE 78 2-(2,3-Dih~droxypropyl~-7~10-dihyaroxy-~-[[2 [(2-hydroxyethyl)amino]ethYl]amino]anthra[l,9-cd]-pyrazol-6(2H)-~ne A mixture of 1.3 g (2 m~ol) of 2-~(2,2-dimethyl-1~3-dioxolan-4-yl~methyl]-5-[~2-[~2-hydroxyethyl)-amino]ethyl~amino-7,10-bis(phenylmethoxy)anthra-[l,9-cd]pyrazol-S~2~)-one~ 260 mg of 20% palladium hydroxide on carbon, and 25 ml of glacial acetic acicl is stirred under an atmosphere of hydrog~n for two hoursO The mix~ure i5 filtered and concen~rated to a residue which is dissolve-l in me~h~nolic hydrogen chloride. The mixture is stirred at room temperature Eor two hours and concentrated to a solid which i~ crystallized from 1:1 methanol:
e~hanol to give 0.7 g of the product 2s a salt with 1.1 equivalents o~ hydrogen chloride solvated with 1.0 equivalent of water; mp jllOC.
2-l(2,2-Dimethyl-1,3-dioxolan-4-yl~methylj-5-[[2 I(2-hydroxyethyl)amino]ethyl]amino-7,10-bis(phenyl-mebhoxy~anthra[l~9-cd]pyrazol-6(2H~-one is prepared as follo-~s:
A mixture of 1.2 g 52 mmol) of 5-chloro~2-[(2,2-dimethyl-1,3 dioxolan-4-yl)methyl]~7 7 l~-bis-~phenylrr~etno~)an~hra[l,9-cd]pyrazol-~(2H)-one, 2.~ m~ t22 mmol) o~ 2-(2-aminoethylamino)ethanol, 17 ml of pyridine, and 0~3 g of anhydrous potassium carbonate is stirred at reElux for 42 hours. The mixture is diluted with water and fil~ered to give a solid that is purified by silica gel chromatography utilizing 94:5:1 dichloromethane:methanol triethyl-amine. Concentration of the product fractions followed by trituration with 2-propanol gives 730 mg of pure product; mp 206C.

~2~5~
CLG-l -117~
5-Chloro-2-~(2 r 2-dimethyl-1,3-dioxolan-~-yl)-methyl]-7,10-bis(phenylmethoxy)ankhrall,9-cd]-pyrazol-6~2~)-one is prepared as follows:
A mixture of 19 6 g (4C ~nol) of 1,4-dichloro-5,8-bis~phenylmethoxy)~9,10-anthracenedione, 10 g (68 n~ol) of 4-(hydrazinomethyl)-2,2-dimethyl-1,3-dioxolan lAnn 448; 121 (1926)], 4 g (69 mmol) of anhydrous potassium fluoride, 5.5 g (40 mmol) of anhydrous ~otassium carbonate, and 150 ml of dry dimethylsulfoxide is stirred a-~ 80C for six hours.
The mixture is diluted with water and the solids are filtered, then dissolved in dichloromethane.
Chromatography of the dried dichloromethane layer over silica gel with gradient elution utili~ing 0O5 ~o 1% net~lanol in dichloromethane gives 6 g of a solid that is triturated from 2-propanol, then crystallized from toluene to aEford 1.8 g of pure product; mp 184-188C.

2-[2-~Diethylamino)ethyl]-7-[[2-~(2-hydroxyeth amino~ethyl]amino]anthra[l,9-cd]pyrazol-6(2H)-o Reaction of 2.5 g (i mmol) of 7 chloro-2-~2~di-ethylamino)ethyl]anthra[l,9~cd]pyrazol-6(2~)-one, 7 ml ~70 ~mol) of 2-(2-aminoethylamino)e~hanol, and 20 ml oE p~ridine or 20 hours a~ reflux followed by workup as described in Example 9 gives 1.6 g of a solid, mp 104-107C, after recrystalliza~ion from toluene. Salt forlnation as described in Ex~mple 3 gives 1~ g of the dried product as a salt with 2.0 equivalents of hydrogen chloride solvated with 1.1 equivalents of water; mp 212-216C (decomposition).
7-Chloro-2-[2-(diethylamino)ethyl]anthra[l,9-ca]-pyrazol6(2~)-one is prepared 25 follows:

t ~.~.5~
CLG-l -118-A mixture of 13.85 g (50 mmol) of 1,5-dichloro-9,10-anthracenedione, 13.1 g (100 mmol3 of (2-diethyl-aminoethyl)hydrazineJ and 100 ml of pyridine is stir-red at 50C for five hours, treated with an additional 10 ml of the substrate hydrazine, stirred at 35C for 48 hours, cooled, filtered, and concentrated.
Trituration of the residue with 2-propanol~ethanol gives 8 g o a solid powder; mp 129-132C.
Dissolution of a 0.9 g sample in hot methanol followed by salt formation as described in Example 3 ~ives 0.8 g of the dried product as a salt with 1.0 equivalent of hydrogen chloride; mp 272-275C (decomposition3.
EX~PLE 80 2-[2-(Diethylamino)ethyl]-7-[[2-(diethylamino)ethyl]-amlno]anthra[l,9-cd]pyrazol-6(2H)-ona Reaction of a mixture of ~.1 g (6 mmol) o~ 7-chloro-2-t2-~diethylamino)ethyl]anthra[1,9-cd]pyrazol-6(2H)-one, 5 ml (36 ~mol) o~ N,N-diethy~ethylenedi- -~amine, and 20 ml of pyridine for 28 hours at reflux followed by workup as des-cribed for Example 21 gives 1.9 g of the dried product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.2 equivalent of water; mp 292-294C (decomposition).

2-~2-~(2-Hydroxvethyl)amino]ethyl]-7-[[2-[(2-hydr ethyl)amino]ethyl]amino]anthra[l,9-cd3pyrazol-6-(2H)-one A mixture o~ 1 9 g (5 mmol) of 7-chloro-2-~2-[(2-hydroxye~hyl)amino3e~hyl~a-nthra~1,3-cd]pyrazol-6(2H3-one, 2.0 ml (20 mmol) o~ 2-(2-aminoethylamino~ethanol, ~ and 20 ml of pyridine is heated at reflux for 72 hours. The mixture is cooled, conce-ntr2ted, and chromatographed over silica gel with 0.5%
triethylamine in dichloromethane, utilizing a gradient elution of 2-10~ methanol, to give the product. Salt fcrmation as described in Example 3 gives 500 ma of - ~5~ 2 CL~ 119-the product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.4 equivalent of water;
mp 285-287C (decomposition~
7-Chlo~o-2-[2-~ hydroxyethyl)amino]ethyl]-anthra[l,9-cd]pyrazol-~(2H)-one is prepared as ~ollows:
A mix~ure of 11.1 g (40 mmol) of 1,5 dichloro-9,10-anthracenedione, 13.1 g (110 mmol) of 2 ~(hydrazinoethyl)amino]ethanol~ 4 9 of anhydrous potassium bicarbonate, 1 g of anhydrous potassium fluoride, and 110 ml of dimethyl sulfoxide is stirred - at 70C overnight. The mixture is chilled and the solids are collected by filtration~ washed with water, then thoroughly with acetonitrile to give a residue that is cr~stalli22d from 2-propanol to leave 2~6 g of product. The hydrochloride salt is prepared as described in Example 3; mp 272-273C (decomposition)~
2~MPLE 82 -7,10-Dichloro-2-[2 E ( 2-hydroxyethyl)amino]ethyl]-5-[[2-[~2-hydroxyethyl)amino]ethyl]amino]anthra-[1,9-cd3~yrazol-6(2H)-one Reac~ion OL 7,10-dichloro-2-[2-[(2-hydroxy-ethyl)aminolethyl]-5-[~(4-methylphenyl)sulfonyl]-oxy3anthratl,9-cd]pyrazol-6(2H)-one/ hydrochloridev with 2-(2-aminoethyla~ino)ethanol gives the product.
7/10-Dichloro-2-[2-[(2-hydroxyethyl)amino]ethyl~-5-l[~4-methylphenyl)sulfonyl]oxy]anthra[l,9-cd]-pyr~zol-6(2~.~)-one is prepared as follows To a suspension of 30~9 g (S0 mmol) of 1~-dichloro-5,8-bis[[(4-methylphenyl)sulfonyl]oxy3-~,10-anthracenedione, 13 ml (75 mmol) of N,N-diisopropylethylamine, and 130 ml of N,N-dimethylformamide at 5C is added dropwise 14.9 g (l~S mmol) of 2-[(hydra~inoethyl)amino]et~anol in 70 ml of .~,N-dimethylformamide. The mixture is allowed ~5~
CLG-l -120~
to reach 10C during five hours, then is diluted with t 20 ml of acetone. After warming to room temperature, ~he solution is concen~rated to an oil that is dis~ributed bet~een water and dichloromethane~
Concentration of the dried dichloromethane layer followed by salt formation as described in ~xa~ple 3 gives 18O1 g of the dried product as the hydrochloride salt; mp 158-160C.
1,4-Dichloro-5,8-bis[[~-methyl2henyl)sulfonyl]-oxy]-9,10-anthracenedione is prepared as follows:
A mixture of 9.3 g (30 mmol) of 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione, 12.6 g (66 mmol~
of p-toluenesulfonyl chloride, 12.2 ml (7Q mmol) of N,N-diisopropylethylamine~ and 120 ml of acetonitrile is heated at 70C ~or one hour, then cooled. The crystals are collected by filtration to leave 14.4 g of dried product; mp 195.~196.5C. Processing oE
the Eiltrates glves 2.2 g of additional product~
mp 19~-192C.
EX~MPLE 83 7-Hydroxy-2-12-[(2-hydroxyethyl)amino]ethyl~-5-[[2-1(2-hydroxye~hyl)amino3e~hyl~amino]anthra[1,9-cd3 . .
~yrazol-6(2~)-one Reaction of a mixture o 2-[2 [(2-hydroxyethyl)~
amino]ethyl]-5-[[2-[(2-hydroxyethyllamino]ethyl]-amino]-7-(phenylmethoxy~anthra~1,9-cd]pyrazol-6(2H) one with hydrogen and 20~ palladium hydroxide on carbon as described ln Example 78 ~ives the product as a salt with 2.0 equivalen~s oE hydrogen chloride solvated with 2.3 equivalents of water; mp 265-270C
(decomposition).
2-12-[(2-hydroxyethyl)amino~ethyl]-5-[[2-[t2-hydrox~f 2 thyl)amino]ethyl]amino-7-(phenylmethyoxy) anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
Reaction of 5-chloro-2-[2-[(2-hydroxyethyl)-amino]ethyl]-7-(phenylmethoxy)anthra[l,9-cd]pyrazol-~-5~ 2 CLG-l -121-6(2H)-one with 2-(2-aminoethylamino)ethanol as described in Example 78 gives the product;
mp 157-159C.
S-Chloro-2-~2-[(2-hydroxyethyl)ami~o~ethyl]-7-(phenylmethoxy~anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
A mixture of 4.2 g (11.0 mmol) oE 1,4-dichloro-5-(phenylmethoxy)-9,10-anthracenedione, 2.6 g ~22.0 mmol) of 2-L(hyra2inoethyl)amino]ethanol, 320 mg (5.5 ~mol) of anhydrous potassium fluoride, 1.1 g (11.0 mmol~ of anhydrous potassium bicarbonate, and 33 ml of dimethyl-sulfoxide is stirred overnight at 80~C, The mixture is cooled and poured into water. The a~ueous mixture is centrifuged and ~he aque~ous phase is decanted to leave an oil that ls dried and purified on sillca gel utilizing 4:1 dichloromethane:methanol as eluting solvent. Concentration o~ the product fractions ~ollowed by trituration ~rom methanol gives 840-~g of the drie~ product; mp 1~1-145C.
1,4-Dichloro-5-~phenylmethoxy)-9,10-anthra-cenedione is prepared as follows:
A mixture of 5.33 g ~18 mmol) of 1,4-dichloro-5-hydroxy-9,10-anthracenedione ~British - Patent 1,029~448), 2.6 g (19 mmol) of powdered anhydrous potassium carbonate, 2.5 ml (21 mmol) of benz~l bromide, ~nd 75 ml of dry acetone is he~ted at reflux overnight. The mixture is cooled ~nd t.he solids are washed well with acetone, Concentration oE ~he Eiltrates gives a solid which is triturated with ether to afford 5,8 g of the dried product; mp 118-122C
Prepared in a fashion similar to 2xample 83 i5 the Eollowing:

~5 CL~ 122--EX~MPLE 8 ! 7-Hydrox~ 2~[(2-hx~_oxyethyl)amino]ethyl1-5-[[
(methylamino)ethyl~amino]anthra[l~9-ca]pyrazol-6(2H) o as a salt with 1.8 equivalents of hydrogen chloride sol~Jated with 1.2 equivalents of water;
mp 280-282C (decomposition) is prepared from 2-[2-[(2-hydroxvethyl~amino~ethyl]-5-[[2-~methyl(phenyl-methyl)amino]ethyl]amino]-7-~phenylm~thoxy)anthra ~l,9-cd]pyrazol~6(2H)-one; mp llO-1139C, which is prepared rom the reaction of N-methyl-N-(phenyl methyl)-1,2-ethanediamine (US Patent 3,201,459~ with 5-chloro-2-12-~2-hydroxyethyl)amino]ethyl]-7-(phenyl-methoxy)anthra[l,9-cd]pyrazol~6~2~)-oneO
EXAMPLE as 10-Hydrox~-2-[~-[~2-~ydroxyethyl)amino]ethyl]--5-~[2-[(2-hydroxyethyl)amino]ethyl]amino]anthra-d ~ razol-6(2~)-one Reaction of.a ~ixture..of..2-E2-[(2-hydro.Yyethyl)-~..r...~ - .~.
amino]ethyl]-5-~2- E ( 2-hydroxyethyl)ami~o]ethy.l.] .-. -amino]~10-(phenylm thoxy)anthra~l,9-cd~pyrazol-6(2~)-one with hydrogen and 20~ palladium hydroxide on car-bon as described in Example 78 gives the product as a salt with 2.1 equivalents of hydrogen chloride sol-vated with 0.8 equivalent of water, mp 260-267C
(decomposition) D
2-[2-[(2-hydroxyethyl)amino~ethyl]-5-~[2 [(2-hydroxyethyl)amino]ethyl]amino-lO~(phenylmethox~
anthrarlJ9-cdlpyrazol-5~2E~~one is pr~par2d ~s follows:
Reaction of 5-chloro-2-[2-[(2-hydroxyethyl~
amino~-ethyl]-10-(phenylmethoxy)anthra[l,9-cd]pyrazol-6~2H)-one with 2--~2-aminoe-thylamino)ethanol as described in ~xample 78 gives the product;
mp 178-180C, 5-Chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]-10-(phenylmethoxy~anthra[1,9-cd]pyrazol-6(2H)-one is prepared as follows:

CLG-l -123-Reaction of 1,~-dichloro-5-~phenylmethoxy)-9,10-anthracenedione wi'h 2-[thydrazinoethyl)a~ino]ethanol as described in ~xample 83 gives the product as the minor isomer; mp 165-167C~

7,9,10-Trihydroxy-2-~2---[(2-hydro~rethxl)amino]ethyl]
5-[~2-[(2=h~droxyethyl)aminolethyl]amino]anthra-[l,9-cd]-pxra~ol-6(2H)-one Reaction of a solution of 2-[2-[(2-hydroxyethyl)-amino]ethyl]-5-[[2-[(2-hydroxyethyl)amino~ethyl~-amino]-7,9,10-tris(phenylmethoxy)anthra[l,9-cd]~
pyrazol-6(2H)-one in glacial acetic acld with hydrog~n and 20% palladium hydroxide on carbon as described in Example 78 gives the product as a salt with 2.1 equivalents of hydrogen chloride solvated with 0.8 equivalen~ of water; mp ~ 235C (decomposition)~
2-[2-[(2-Hydroxyethyl)amino]ethyl]-5-~[2-[(2-. _. hydroxyethyl)amino]ethyl]amino]-7.,9,10-tris(phenyl-methoxy)anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
A mixture o 660 mg (1 mmol~ of 5-chloro-2-[2-~(2-hydroxyethyl)amino~ethyl]-7,9,10-tris (phenyl-methoxy~anthra[l,9-cd]pyrazo1-6(2H)-one, 1 ml (10 mmol) of 2-(2-aminoethylamino)ethanol, and 2 ml of pyridine is heated at reflux for 28 hours, Workup as described in Example 21 gives a solid whose crystallization from acetonitrile chloroform afEords 308 mg of product; mp 158-159C, 5-Chloro-2-[2-[(2-hydroxyethyl)amino]e~hyl]-7,9,10-tris(p'nenyl~etho~y)anthra~l,9-cd]pyrazol-6(2H)-one is prepared as fo1lowsO
A suspension of 7.2 g (12 ~mol) of 5,8-dichloro-1,2,4-tris(phenylmethoxy)-9,10-anthracenedione, 2 g g (2~ mmol) of 2-[(hydra~inoethyl)amino]ethanol, 350 mg ~6 mmol) of ~nhydrous potassium flouride, 1.2 g (12 mmol) of anhydrous potassium bicarbonate, and 25 ml of dimethylsulfo~ide is stirred overnight a~

CLG~ 124-75C. The mixture is cooled7 then triturated with 2-~ropanol. The solids are filtered, ~ashed well with water, 2-propanolJ then crys~alli2ed from chlorororm to give 2~3 g of orange solid; mp 172-:L73C, Processing of the nonaqueous filtrates gi~es 640 mg of additional product corresponding to ca. 1:1 mixture of isomers by 1H ~IR, ~P 135-140C, 5,8-Dichloro-19 2,4-tris(phenylmethoxy) 9,10-anthracenedio~a is ~repared is as ollowsO
A suspension of 7.5 g (23 mmol~ of 5,8~dichloro 1,2,4-trihydroxy-9,10-anthracenedione, 9,6 ml (81 m~ol) or benzyl bromide7 9.9 g (72 mmol) of powdered anhydrous potassium carbonate, 00~ ml of methanol r 92 ml of acetone, and 46 ml of dimethylformamide is heated a~. reflux under argon for two days. An additional ~.7 ml of benzyl bromide is added and ~he mixture is heated for ~hree days.
The suspension is filtered and-the filtrate is~
concentrated to an oil w~ich i5 distributed between~
dichloromethane and 10~ aqueous acetic acid~ The dried dichloromethane layer is concentrated to a solid whose crys~allization from ethyl acetate affords 7.2 g of product; mp 174-175Co 5,8-Dichloro 1,2~-trihydroxy-3,10-anthracenedione is prepared as follows:
A suspension of 451 mg (1 mmoll of 1,2,4-tris ~acetylox~)-5,8-dichloro 9,10-anthracenedione~ 5 ml of g].acial ac2tic acid~ and 5 ml o~ 6 N ~queous hydro-chloric acid is hea~ed a~ 70~ or ona hour. The suspension is cooled and the solids are filtered off.
After washing with water and drying, there remains 287 mg oE the dried product; mp 790-295C
decompos ition ~ ~ -1,2,4-Tris(acetyloxy)-5,8-dichloro-9,10-anthracenedione is prepared as follows:
A suspension of 307 mg (1 mmol) of 5,8 dichloro 1~4,9,10 anthracenetetrone, 0.05 ml of 72~ perc~loric ~5 CLG-l -125-acid, and 10 ml of acetic anhydride is stirred at room temperature for 30 minutes The soluti.on is . diluted with water, the organic layer is separated, and dried, ~hen concentrated to a solid residue.
Trituration of the solid from ethyl acetate leaves 235 mg of product; mp 205-206Co 5,8-Dichloro-1,4,9,10-anthra~enetetrone is prepared as followsO
A suspension of 618 mg 12 ~mol) of 1,4-dichloro-5,8-dihydrsxy-9,10-anthracenedione, 1.06 g (2.4 mmol~
of lead tetraacetate, and 25 ~1 of glacial acetic acid is stirred at room temperature for 45 minutes~ The mixture is treated with 0.5 ml ethylene glycol, and ater 15 minutes is diluted with dichloromethane.
The mixture is ~ashed with water and the dried organic layer is evâporated ~o a solid~ Trituration of the solid from diethyl ether gives 569 mg of product;
~p 255-257C (decompGsition)i ~
EX~MP~E 87 7~8~10-Trihydroxy-2-[2-[(2-hydroxethyl)amino]ethyl]
5-l[2-[(2-hydroxyethyl)amino]ethyl]am no]anthra-[1,9-cd]pyrazol-6(2~)-one Reaction of a solution of 2-[2-~(2-hydroxyethyl)-amino]ethyl]-5-[[2-~(2-hydroxyethyl)amino]ethyl~
amino]-7,8,10-tris(phenylmethoxy)anthra~l,9-cd]-pyrazol-5(2H)-one in glacial acetic acid with hydrogen and 20% palladium hydroxide on carbon as described in Example 78 gives the produc~ as a sal~ with 2.1 equi~7alents of h~drogen chloride solvated with 0,~
equivalent of water; mp >210C (decomposition).
2-~2-[(2-~ydroxyethyl)a~ino]ethyl]-5-[~2-[(2-hydroxyethyl)amino]ethyl]amino~-7,8,10-tris(phenyl-~ethoxy)anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
Reaction o~ 5-chloro-2-[2-~(2-hydroxyethyl)-amino]ethyl]-7,8,10-tri~phenylmethoxy)anthra[1,~-cd]-~5~2 CLG~l -126~
pyrazol-6(2H)-one with 2-~2 aminoethylamino)ethanol as described in Example 86 gives the product;
mp 186-188~C~
5-Chloro-2 [2-1(2-hydroxyethyl)amino]ethyl]-7,~,10-tris(phenylmethoxy~arlthra[1,9rcc!]pyra~ol-6(2H)~one is prepared as follows:
Reaction of 5,8-dichloro-1,2,4-tris(phenyl-methox~)-9,10-anthracenedione with 2-[(hydrazino-ethyl)amino]ethanol as described in Example 86 gives the product as the minor isomer; mp 164-167~Co Prepared in a fashion similar to Exam~le 87 is the following:

7,8~10-rrihydroxy-2-[2-[(2-hydroxyet-hyl)amino)-~ethy].]~
5-[[2-(methylamino)ethylIamino]anthrall,9-cd]
~yrazol 6(2H)-one as a salt with 2.0 equivalents oE hydrogen chloride solvated with 0.7 equivalent of water; mp ~220C (decomposition), which is prepared from 2 [2-[(2-hydroxyethyl)amino]ethyl]-5-~L2-[methyl(phenylmethyl)amino]ethyl~amino]-7,8,10-tris (phenylmethoxy)anthra[l,9-cd~pyrazol-6(2H)-one;
mp 104-108aC which i5 prepared from the reaction of N-methyl-N(pn~nylmethyl)-1,2-ethanediamine with 5-chloro-2-[~-1(2~hydroxyetIlyl)amino]ethyl]
7,8,10-tris(phenylmethoxy)anthra~l,9-cdIpyrazol-6(2~)-one.
EXA~P~E 89 _-[l2-[(2-Aminoethyl)amlno~e~hyl]amino]-7,10-dihvdroxv 2-(2-hYdroxvethvl)an~hra[l,9-cd~-_ pyrazol-6(2B)-one Reaction of a solution of 5-[12-[(2-aminoethyl)-amino]ethyl]amino-2-(2-hydroxysthyl)-7~10-bis(phenyl-me~hoxy)anthrall,9--cd3pyrazol-6(2H)-one in glacial acetic acid with hydrogen and 20~ palladium hydroxide on car~on as described in Example 78 gives the product as a sal~ with 2.4 equivalents of hydrogen chloride solvated with 008 e~u.valent of water; mp 170-185C
(decomposition).

~S~ 2 CLG-l -127-5-~[2-[(2-Aminoethyl)amino]ethyl]amino-2-(2-hydroxyethyl)-7,10-bis(phenylmethoxy)anthra[l,9-cdl-pyrazol-6(2H)-one is prepared as follows A mixture of 501 g (10 mmol3 of 5--chloro-2-12-hydrox~yethyl)-7,10-bis(phenylm.ethoxy)anthra~l,9-cd3-pyrazol~6(2H)-one, 10 g (100 mmol] of cliethylene-triami.neJ 1.4 g (10 mmol) of anhydrous potassium carbonate, and 60 ml of pyridine is heated at reflux for 28 hours. The mixture is cooled, the solids are collected by filtration then washed sequentially with water and 2-propanol to give 3.1 g of the product;
mp 185-190C.
EXAMPLE gO
2-~3-Amino~ro~yl)-7,10-dihy_~oxy-5-~2-[(2-hydroxy-ethyl~aminole~hyl]amino~anthra[l,9-cd]l~yrazol-~2H)-one Reaction of a solution of 1.2 g (2 mmol) o~
-2~(3-aminopropyl)-5-[~2-[(2-hydroxyethyl)amino]ethyl]
amino]-7,10-bis(phenylmethoxy)anthra~1,9-cdlpyrazol-6~2H)-one in glacial acetic acicl with hydrogen and 20 palladium hydroxide on carbon as described in Example 78 ~ollowed by salt formation as described in Example 3 gives 850 mg of the product a salt with 2.0 equi-~ralents of hydrogen chloride solvated with 1.1 equi-valents of water; mp 292-294C (decomposition)~
2-(3-Aminopropyl)-5-[ L 2-[(2-hyroxyethyl)amino]
ethyl]amino-7,10-bis(phenylmethoxy)anthra[l,9~cd~-pyrazol~ M)-one ls prepared as follows~
A mi~ture of ~30 mg (1 mmol~ of 2-(3-amino-propyl)-5-chloro-7,10-bis(phenylmethoxy)anthra-1,9-cd3pyrazol-~(2H)-one, 1 ml (10 mmol) of 2-(2 aminoethylamino)ethanol, 140 mg (1 m~ol) of anhydrous potassiu~ carbonate, and 8 ml of pyridine is heated at refluY~ for 22 hours. Workup as described in Example 89 gi~es 400 mg of the product; mp 191-195C.
2-(3-Aminopropyl)-5~chloro-7,10-bis-(phenylmethoxy)anthra[1,9-cd]pyrazol-o(2~)-one is prepared as follows:

s~

CLG-l -128-Reac~ion of a mixture of 1,4-dichloro-5,8-bis-tphenylmethoxy)-9,10-anthracenedione and (3-amino-propyl)hydr~zine ~Helvetica Chimica Acta 42; 533 (1959)~ as described in Example 54 sives the product;
mp 180-184~C.
Prepared in a fashion similar to :Example 90 is the following:
EX~MPLE 91 2-(3-~minopro~yl)-5-[[2-~2-(dimethylaJnino)ethy1]-amino~ethyl]amino]-7,10-dihydroxyanthra[l;9-cd~
pyrazol-6(2H)-one as a salt with 3~0 equivalents of hydrogen chlo-;ide solvated with 2.0 equivalents of water; mp 294C (decomposition), which is prepared fro~n 2-(3-aminopropyl~-5-[[2-[[2 (dimethylamino)-ethyl]amino]ethyl]amino]-7,10-bis(phenylmethoxy) anthra[l,9-cd]pyrazol-6(2H)-one; mp 143-160C, which is prepared from the reaction of N,N-dimethyldi-ethylenetriamine with 2-(3-aminopropyl)-5-chloro-7,10-bis(phenylmethoxy)anthra[l,~-cd]pyrazol-6(2~)-one.

2-~2-Aminoethyl)-7,10-dihydroxy-5-~[2-(methylamino ? -ethyl]amino]anthra[l,9-cd]Pyrazol-6(2~)-one Reaction of a mixture of 2-(2-aminoethyl)-5-l[2-methyl(phenylmethyl~amlno]ethyl]amino]-7 r 10-bis-tphenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one with hydrogen and 20% palladium hydroxide on carbon as described in Example 78 gives the product as a salt with 2~7 equivalents of hydrogen chloride solvated with O.S equivalent of water; mp 259-264C
tdecomposition).
2-~2-Aminoethyl)-5-[[2~[methyl(phenylmethyl)-a~ino]ethyl]amino]-7,10-bis(phenylmethoxy)anthra[1,9-cd]pyrazol-6(2H)-one is prepared as follows:
Reaction of 2-(2-aminoethyl)-5-chloro-7,10-bis-(phenylmethoxy)anthra[1,9-cd~pyrazol-6t2H)-one with CLG-l -129-_-methyl-~-(phenylmethyl)-1~2-ethanediamine as de-scribed in Example 7~ gives the product; mp 169-172C.
EX~,~PLE 93 7,10-Dihydroxy~5-[[2-[t2-hydroxyet~ )alr.ino]ethyl]-amino~-2-[2-(methylamino)ethyl]anthra[l,9-cd]pyra 6(2H)-one Reaction of a mixture of 5-[[2-[(2-hydroxyethyl~-amino]ethyl]amino]-2-[2-(methylamino)ethyl]-7,10-bis-(phenylmethox~)anthra[l,9-cd]pyrazol-6(2H) one with hydrogen and 20~ palladium hydroxide on carbon as described in Example 78 gives the product as a salt with 2.0 equiYalents of hydroyen chloride solvated with 1.8 equivalents of water; mp 180-185C
(decomposition)O
5-[~2-l(2-hyc~-coxye~hyl)amino]e~hyl]amino~-2-[2-(methylamino)ethyl]-7,10-bis(phenylmethoxy)anthra-[1,9-cd]pyrazol-6(2H)-one is prepared as Eollows:
Reaction of 5-chloro-2-[2--(methylamino)ethyl]- ~~
7,10-bis(phenylmethoxy)an.thra[l,9-cd]pyrazol-6(2H)-one with 2-~2-aminoethylamino)ethanol as described in Example 78 gives the product; mp 185-189C
5-Chloro-2-~2 (methylamino)ethyl]-7,10-bis-(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follo-~s:
~ eaction of 5~chloro-2-[3-[~4-methylphenyl)-sulfonyl]oxy]ethyl]-7910-bis(phenylmethoxy)anthra-[l,9-~d]pyrazol-6(~H)-one ~ith methylamine as-de-scribed in ~xample 51 give~ the product; mp 171-176C.
EXAMPLE ~4 2-Aminoethvl)amino]-2-[3-(dimethylaminO)~rOpYl]-7,10-dihydroxyanthxa[l~9-cd]pyra2ol=6~2H)-one _ Reac~ion of 5-chloro-2-[3-(dimethylâmino)propyl]-7,10-dihydroxyanthra[l,g-cd~pyrazol-6(2~)~one, hydro-chloride, with ethylenediamine as described in Example 46 gives the product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.5 equivalent 5~
~LG-l -130- -of water and 0.1 equivalent of 2-propanol; mp 316C
; (decomposition).

7,8-DihydroxY- _ (2-hy~roxyethyl)amLno]ethyl]-5 [[2-[(2-hydroxyethyl?amino]ethyl]aminolanthra[l~9-cd]
pyrazol-6(2H~-one Reaction of a mixture of 2-[2-[(2-hydroxyethyl)-amino]ethyl]-5-[[2-[(2-hydroxyethyl)amino]ethyl]-amino]-7,8-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one with hydrogen and 20% palladium`hydroxide on carbon as described in Example 78 gives the product.
2-~2-~t2-hydroxyethyl)amino]ethyl]-5~[[2-[(2-hydroxyethyl)amino]ethyllamino]-7,8-bis-(phenylmethoxy)anthra[1,9-cd]pyrazol-6(~H)-one is prepared as follows:
Reaction of 5~chloro-2-[2-[(2-hydroxyethyl)-amino~ethyl]-7,8-bis(phenylmethoxy)anthra[l,9-cd]
pyrazol-6(2H)-one with 2-(2-aminQethylamino)ethanol as descrlbed in Example 78 gives the product.
S-Chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]-7,8-bis(phenyl~ethoxy)anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
Reaction of 1,4-dichloro~5,6-bis(phenylmethoxy)~
9,10-anthracenedione with 2-[(hydrazinoethyl)amino]-ethanol as described in ~xample S4 gives the product~
1~4-Dichloro-5,6-bis(ph~nylmethoxy) 9,10-an-thracenedione is prepared as fGllows:
Reaction of 1,4-dichloro-5,6-dihydroxy-9,10-anthracenedione with benzyl bromide as described in Example 48 gives the product.
1,4-Dichlcro-5,6-dihydroxy-9,10-anthracenedione is prepared as follows:
Reaction of nitrosyl sulfuric acld and 5,6-~iamino-1,4-dichlsro-9,10-anthracenedione fxhim .
Geterotsikl. Soedin. 808 (1968)] gives the prcduct.
. _

Claims (8)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for preparing a compound of general formula:

(VII) wherein:

Z represents a group selected from H, C1-6alkyl, ORl-substituted-C1-6alkyl, SR1-substituted-C1-6aklyl, N(R1)2-substituted-C1-6alkyl and -DNR2R3' wherein:
D represents a group selected from C2-8alkylene and OH-substituted-C2-8alkylene, R1 represents a group selected from H and C1-6alkyl, and R2 and R3, independently, represent a group selected from H, C1-6alkyl, OH-substituted-C1-6alkyl, N(Ra)2-substituted-C1-6alkyl and N(Rb)2-substituted-C1-6alkyl, wherein Ra represents a group selected from H, C1-3alkyl and OH-substituted-C1-3alkyl, and Rb represents a group selected from H and C1-3alkyl, or R2 and R3, when taken together, represent a group selected from -CH2CH2- and , wherein m and n, independently, are one, 2 or 3, with the proviso that m+n is an integer of from 3 to 6, and B represents a group selected from a direct bond, -O-, -S- and -N(R4)-, wherein R4 is as defined above for R1;
said process comprising:
(a) reacting a compound of general formula:

with a hydrazine of general formula H2N-NHZ, wherein Z is as defined above; and (b) recovering the desired product from step (a); or (c) when required, preparing a pharmaceutically acceptable salt from the product of step (b).

2. A compound of general formula:

( V I I) wherein:

Z represents a group selected from H, C1-6alkyl, OR1-substituted-C1-6alkyl, SR1-substituted-C1-6aklyl, N(R1)2-substituted-C1-6alkyl and -DNR2R3, wherein:
D represents a group selected from C2-8alkylene and OH-substituted-C2-8alkylene, R1 represents a group selected from H and C1-6alkyl, and R2 and R3, independently, represent a group selected from H,

Claim 2 contd. 3 C1-6alkyl, OH-substituted-C1-6alkyl, N(Ra)2-substituted-C1-6alkyl and N(Rb)2-substituted-C1-6alkyl, wherein Ra represents a group selected from H, C1-3-alkyl and OH-substituted-Cl-3alkyl, and Rb represents a group selected from H and C1-3alkyl, or R2 and R3, when taken together, represent a group selected from -CH2CH2- and , wherein m and n, independently, are one, 2 or 3, with the proviso that m+n is an integer of from 3 to 6, and B represents a group selected from a direct bond, -O-, -S- and -N(R4)-, wherein R4 is as defined above for Rl;
and a pharmaceutically acceptable salt thereof.

3. 7-Chloro-2-[2-(diethylamino)ethyl]anthra[l,9-cd]-pyrazol-6(2H)-one, and a pharmaceutically acceptable salt thereof.

4. 7-Chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]anthra--[l,9-cd]pyrazol-6(2H)-one, and a pharmaceutically acceptable salt thereof.

5. 2-[(Hydrazinoethyl)amino]ethanol.

6. A process for preparing 2-[(hydrazinoethyl)amino]ethanol, comprising:
reacting hydrazine and N-(2-hydroxyethyl)aziridine; and recovering the desired product.

7. 5,8-Dichloro-1,4,9,10-anthracenetetrone.

8. A process for preparing 5,8-dichloro-1,4,9,10-anthracenetetrone, comprising: oxidizing 5,8-dichloro-1,4-dihydroxy-9,10-anthracenedione; and recovering the desired product.