CA1256431A - Substituted anthra¬1,9-cd|pyrazol-6-(2h)-ones - Google Patents

Abstract

ABSTRACT

Substituted anthra[1,9-cd]pyrazol-6(2H)-ones having antimicrobial activity, methods for their preparation and use, and pharmaceutical compositions containing them are disclosed.
The novel compounds have the general formula:

wherein R is H or C1-6alkyl, and Y and Z are aa defined in the disclosure and claims. The novel compounds are prepared by reacting an amine of general formula: HNRY with a compound of general formula:

Description

~25~3~
~`his is a divisional application of copending application, serial no. 432,584, filed July 18, 1983.
BACKGROUND OF THE INVENTION
Several 2,5 and 2,7-disubs-tituted anthra[l,9-cd]pyrazol 6(2H)-ones are disclosed in the prior literature. See for example J. Chem. Soc., 1630 (1952); J. Chem. Soc., 1894 (1954). Neither reference discloses any utility for these compounds.

SUMMARY OF TH~ INVENTION

The invention in its first generie chemical eompound aspect is a compound having the structural formula Nl - ~I-Z

~
X O NR'~

wherein X, X' and W may be the same or difrerent and are hydrogen, hydroxy, alkoxy having one to four earbon 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 branehed alkylene of from two to eight earbon atoms, R2 and R3 may be the same or different and are H, alkyl of from one to six earbon 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 _ ~5~3~
or different and is H or alkyl of from one to three carbon atoms, or R2 and R3 when taken together may be ethylene or may form -(CH2)n~

~(C~2);n/

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-~(CH~)n~ \

-(CH2)m /
wherein n and m and B are defined above; Z is H, alkyl of ~rom one to six carbon atoms which may be substi-tuted with an ~(Rl)2, SRl, or ORl group wherein Rl is the same or different and is defined above, or DNR2R3 wherein D is straight or branched al',~ylene of from tt~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 acceptable salts thereof; with the following provisos, 1) when X, ~' and W are H and Z is H, R and Y when taken together 20 not complete a piperidine ring, 2) when X, Xl, 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 .ormula N - N-Z
W~

X' O NRY

wnerein X, X' and W may be the same or different and are H or 0~, alkox~l having-one to four carbon atoms or chlorine; R is H or alkyl of from one to six carbon atoms; Y is H, alkyl of Erom one to six carbon atoms which may be substitutsd with an P~l group wherein Rl is H or alkyl of from one to six carbon atomsr or A~R~R3 wherein A i5 Strâight or ~ranched ~ ylene oF from tt~o to eight carbon atoms, R2 and ~33~

R3 may be the same or different and are H, alk~l of from one to si~ carbon atoms ~hich may be sllbstiLuted with OH or an ~RaRa wherein Ra may be the same or different and is ~ or alkyl o from one to three carbon atoms whic~ may be substituted with OH, or NRbRb wherein Rb is the same or dirferent and is H
or alk-yl Oe from one to three carbon atoms, or R2 and R3 when ta~en together may be ethylene or may form -(CH2)n\
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 i5 an integer of Erom three to six, and B is a direct bond, O, S, or N-R~ wherein R4 is H or alkyl of ~rom one to six carbon atoms; R and Y when taken together may be ethylene or may form -(CH2)n\
B
-(CH2)m /
wherein n~ m, and B are defined above; Z is ~, alkyl o rom one to six carbon atoms which may be substituted with an II(Rl)2, SRl, or ORl group wherein Rl is the same or different and is defined above, or DN~2R3 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 acceptable salts~ tnereof; with the following provisos, 1) when X, X', and W are H and Z is H, R and Y when taken together do not complete a piperidine ring, 2) when X, X', and -~1 are H and Z is CH3 R and Y when taken together do not complete a piperidine ring or a morpholine ring.

-~l2'5~
CL5-1 ~5~
lhe invention sought to be patented in its ! third generic chemical compound as?ect i5 a corn~ollnd having the st.uctural formula N ~I-z X~

I

X ~ NR'~

wherein X and X' may be the same or differen~ and are ~, OH, alkoxy of one to four carbon atoms or chlorine;

is ~ or alktyl of from one to six carbon ato~s; Y is ~, alkyl of from one to six carbon atoms which may ~e substitu~ed with an ORl group wherein Rl is ~I or alkyl of from one to six carbon atoms, or ANR2R3 wherein A is alkylene of from two to 11 carbon atoms, R2 and R3 may be the same or diCferent and are H, al'~yl o ~rom one to six carbon atoms which may be substituted with OH or an NRaRa wherein Ra is H or alXyl of from one to t'nree carbon atoms which may be substituted with OH, or NRbRb wherein Rb is the same or difCer~nt and i9 '~ or alkyl o~' from one to ~h-ee ca-~on atoms, or R2 and R3 when taXen together may be et~ylene or may form ~(C~2)n\

-(CH2)m /
wherein n, m, and B are defined'above; % is H, alkyl of ~rom one ~o six carbon atoms which may be substituted with an M(R1~2, SRl, or ORl group wherein Rl is defined above, or DNR2R3 wherein D i5 alk~lene oE fro~ two to 11 carbon atoms which may be substituted with an OH group and R2 and R3 are as defined above;
and the p~armaceuticall~ acceptable sal~s thereof; with the Collowing provisos, 1) when X is H and Z is H, R
J

~$T~;~3~

and Y when taken ~ogether do not complete a piperidine ring, 2) when X is H znd Z is CH3 R and Y whsn tal~en together do not complete a piperidine ring or a morpholine ring.

~(CH2)n\B
-(CH2)m/
wherein n, m, and B are defined aboYe; Z is H, alkyl of from one to six carbon atoms which rnay be substituted with an ~(~1)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 b2 substituted wl'h an OH group and R2 and R3 are as defined above;
and the pharmaceutically acceptable salts thereof; with the followiny provisos, 1) when X is H and Z is H, R
and Y when taken together do not complete a piperldine ring, 2) when X is H and Z is CH3 R and Y when taken together do not complete a piperidine ring or a morpholine ring.
The invention in its fourth generic chemical compound aspect is a compound having the structural formula I

1~, ~1 ~' O ~'f I
wherein X, and X' may ke the same or diferent and are H or OH; R is H or alkyl of from one to si~ carbon atoms; Y is H, alkyl of from one to six carbon atoms which may be substituted with an ORl group wherein Rl is ~ or alXyl o~ from one to six carbon atoms, or ~NR2R3 ~herein ~ is straight or branched alkylene of from two to eight carbon atoms, R2 and R3 may be the same or ~ifferent and ar ~, al~yl of frsm one to ~i~
car~on atoms which may be substituted with Ofl or an NRaRa wherein ~a is tne same or different and as ~ or al~yl of from one to three carbon atoms which may be substituted with OH, or NRb~ wherein Rb is the same or different and is H or alkyl of 'rom one to three carbon atoms, or R2 and R3 when taken together may be ethylene or may form -(C~2!n~B

~(C~2)m/
and m is an integer of from three to si~, and B is a direct ~ond, O, S, or N-R4 ~herein R~ is H or alkyl of from one to si~ carbon atoms; R and Y when taken together may be ethylene or may form ~(CEI2)n\B
/
-(CH2)m wherein n, m, and B are defined above; Z is H, alkyl of from one to six carbon atoms which may be substituted with an N(Rl)2, SRl, or ORl group wherein Rl is the same or different and is as defined above, or DNR2R3 wherein D is straight or branched al~lene 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 acceptable salts thereof; with the following provisos, 1~ when X
and Xl are H and Z is H, R, and Y when ta'~en together do not complete a piperidine ring, 2) when X and X' are ~ and Z is CH3, R and Y ~hen taken together do not complete a piperidine ring or a morpholine ring.
The invention in a first s~bgeneric aspect of its fourth chemical compound aspect is a chemical compound having structural formula I wherein X and X' are OH;
and the pharmaceutically acce~table salts t~ereof.

CLG-l -9-The inven~ion in a second subgeneric aspert o~
its fourth chemical compound aspect is a chernical compound having struc~ural 'ormula I ~herein X an~ X' are H; and the pharmaceutically acceptable salts thereof .
The ~nven~ion in a third subgeneric aspect of its Eourth chemical compound aspect is a chemiczl compound ha~ing structural formula I wherein A a.nd D are the same or different and are ethylene or propylene; and the pharmaceutically acceptable salts thereof.
The invention in a fourth subgeneric as~ect of its fourth chemical compound aspect is a compound having structural ~ormula I' N - N-Z' O NR'Y' I' wherein R' is H or alkyl of from 1 to ~ carbon atoms;
Y' is CH2CH2NHCH2CH20H when Z' is al~yl of from one to four carbon atoms which ma~ be substituted with an SRl, or ORl group wherein Ri is H or alkyl of from one to four carbon atoms or D'NR2~3 wherein D' is strai~ht or branched al~lene of from two to four c,a~bon atoms which may be substitute~ with an OH group and P~2 and R3 may be the same or diEferent and are H, alkyl of fro~ one to six carbon atoms whlch may be substituted with an OH or R2 and R3 when taken together may be ethylene or may form (C~2)n' \
B' i ' -(CH2)~ /

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-R4 wherein R4 is H 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 havin~
structural formu.a I'' HO 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 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 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'' \B'' -(CH2)1n' '/
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 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 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 N - 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 ~hlch may 'oe substituted with ~n OH or R2 and R3'' when taken together may be ethylene or ma~
form -~c~2)n' ' ' -(CH2)m''' wherein n''' and m' " may be tne same or dif erent and are one or two provided that ~he sum of n''' and m''' is three or four, 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 SRi , or ORL group wherein Rl is defined a~ove, 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 seventh subgeneric aspect Oc its fourth chemical compound aspect is a compond haYing the structural formula I'' "
Nl N-Z'''' OH o NR''''Y " '' I'''' ~herein R'''' is H or alkyl oE from one to six carbon atoms; '~" " 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 R~
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 CLG-l -13~
carbon atoms ~Ihich may be substituted with an OH or an ~Ra''''Ra''l' wherein Ra " '' is the sa~e or different and is H or alkyl of f~om one to three car~on atoms which may be substituted with an OH or ~2 and R3 when taken together may be ethylene or may form ~(C~2)n-'''\
B' " ' -Ic~2)m~ ' wherein n'' " and ml''' may be the same or different and are one or two provided that the sum of n" '' and m'''' is three or four, and s " '' is a direct bond, O, S, or N-R~ wherein R4 is H or al~l o from one tc four carbon atoms; Z'''' is ~lkyl oE from one to four carbon atoms which may be substituted with an SRl , or oRi group ~-herein Rl is defined above or D''''NR~ R3 wherein D" '' is al~ylene 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 an eigh~h ~ubgeneric aspect of its fourth chemical compound aspect is a compound havin~ tne structural formula Iv N N_zv NRvyv IV

~2~

CLG-l -14-wherein Rv is H or alkyl of from one to six carbon atoms; yv is H, alkyl of from one to four carbon atoms or AVNR2vR3v ~herein A'~ is alkylene of from two to four carbon atoms, ~2Vand R~ may be the same or different and are ~ or alkyl of from one to six carbon atoms which may be substituted with an O~ or R2V and R3v when taken together may be ethylene or may form -(C~12)n -(CH2)mV~
wherein ~ and mV may be the same or different and are one or two provided that the sum of nV and mV is three or four, and sv is a direct bond, O, S, or NR4V wherein R4v is H or alkyl of from one to four carbon atoms; zv is alkyl of from one to four carbon atoms, which may be substituted with an S
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 R2V 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 ~,.
~ O NRVlY
Ivi CLG-l -15-wherein R~Ji is H or alkyl of from one to six car~on atoms; ~vi is H, alkyl of from one to four car~on atoms which may be substituted with an oRlVi group wherein RlVi is H or alkyl of from one to four carbon atoms or AViNR2viR3vi wherein ~vi is alkylene of fr~m two to four carbon atoms R2Vi and R3Vi may be the same or different and are alkyl of from one to six carbon atoms which may be substituted with an OHt or R2vi and R3Vi when taken -together may be ethylene or may form -(CH2)nVi\
3Vi -(CH2)mVi wherein n'~i and mvi may be the same or different and are one or ~ o provlded that. the sum of nVl and mvi is three or four, and BVi is a direct bond, O, S, or NR4Vi wherein R4Vi is H or al~yl o~
from one to four car~on atoms; zvi is DViMR2viR3vi wherein DVi is all~ylene of from two to four carbon atoms, R2Vi and R3Vi are defined above; and the pharmaceutically acce2table salts thereof.
The invention as species of the first generic chemical compound aspect of the invention are the chemical compounds having the following names:

2-[2-(diethylamino)ethyl)]-5-[[2-[(2-hydroxyethyl)-amino]ethyl3amino]anthra[1,9-cd]pyrazol-6(2H)-one;
2-[2-~(2-hydroxyethyl)amino]ethyl3-5-[[2-[(2-hydroxy-ethyl)amino]ethy'l3amino]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-dihydro~y-5-[[2-[(2-hydroxyethyl)amino]ethyl]amino]antllra~l,9-cd]-pyrazol-6(2H)-one;

.3~
CI,G-l -16-5-[[2-[(2-hydroxyethyl)arnino]ethylja~ino]-7,10-: dihydroxy-2-(2-hydroxyethyl)anthra[1,9-c~]pyrazoi-6(2H)-one;
2-[2-[~2-(dimethylamino)ethyl]amino]ethyl]-5-[[2--[(2-hydroxyethyl)amino]ethyl]amino]-7,10-dihydroxyanthra-ll,9-cd]pyra2ol-6(2H~-one;
2-[2-(diethylamino)ethyl]-[[2-(4-morpholinyl)ethyl)l-amino]anthra[l,9-cd]pyrazol-6(2H)-one;
2-(2-aminoethyl)-5-[[2-[(2-hydroxyethyl)amino]ethyl]-amino]anthra[l,9-cd]pyrazol-6~2H~-one;
5-[(2-aminoethyl)amino]-2-[2-(dier.hylamino)ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
2-[2-(diethylamino)ethyl]-7,10-dihydroxy-5-[[2-(methylamino)ethyl]amino]anthra[l,9-cd]pyrazol-6(2H)-one;
2-[2-(dimethylamino)ethyl]-7,10-dihydroxy-S-[~2-[(2-hydroxyethvl)amino]ethyl]amino]anthra~l,9-cd]pyrazol-6(2H)-one;
5-[(2-aminoethyl~amino]-2-[2-(dimethylamino)ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
5-[(3-aminopropyl)amino]-2-[2-(dimethylamino)ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
5-[(2-aminoethyl)amino]-7,10-dihydroxy-2-(2-hydroAy-ethyl)anthra[l,9-cd]pyrazol-6(2~)-one;
5-[[2-(dimethylal~ino)ethyl]amino]-7,10-dihydroxy-2-(2-hydroxyethyl)anthra[l,9-cd]pyrazol-6(2H)-one;
2-[3-(diethylamino)-2-hydroxypropyl]-7,10-dihydroxy-5-[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthra-~1,9-cd]-pyrazol-6(2H)-Gne;
5-l(2-aminoethyl)amino]-~-l3-(diethylamino)-2-hydr propyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
2-[3-(dimethylamino)propyl]-7,10-dihydroxy-5-[[2-1(2-hydroxyethyl)amino]ethyl]amino]anthra[l~9-cd]
?YraZol-6(2H)-one;

~æs~3~
CLG-l -17-7,10-dihydroxy-5-[[2-[(2-hydroxyethyl)amino]ethyl]-amino]-2-[2-[(2-hydroxyethyl)methylamino]ethyl]-anthra[l,9-cd]pyrazol-6(2H)-one, 7~l0-dihydroxy-S-~[2-[(2-hydroxyethyl)amino]ethyl]-amino]-2-f3-l(2-hydroxyethyl)amino]propyl]anthra-[l,9-cd]pyrazol-6(2_)-one;
5-[(2-aminoethyl)amino]-7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]anthraLl,9-cd]pyrazol-6(2H)-one;
5-[[2-(dimethylamino)ethyl]amino]-7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]anthra[l,9-cd]-pyrazol-6(2H)-one;
5-[12-(diethylamino)ethyl]amino]-7,10-dihydroxy-2-[2-1(2-hydroxyethyl)amino]ethyl]anthra[1,9-cd]PYrazol-6(2~)-one;
5-[(3-aminopropyl)amino]-7,10 dihydroxy-2-~2-[(2-hydroxyethyl)amino]ethyl~anthra[l,9-cd]pyrazol-6-~2H)-one;
7,10-dihydroxy-2-[2-[(2-hydroxyethyi)amino]ethyl]-5-~[3-[(2-hydroxyethyl)amino]propyl]amino]anthra[l,9-cd]pyrazol-6(2~)-one;
5-[[2-[[2-(dimethylaminoethyl]amino]ethyl]amino]-7,10-dihydroxy-2-[2-[~2-hydroxy~thyl)amino]ethyl]anthr2-tl,9-cd]pyra~ol-6(2H)-one;
5-[[2-[(2-aminoethyl)amino]ethyl]amino]-7,10-di-hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyllanthra-[l,9-cd]-pyrazol-6(2H)-one;
5~[[2-[bis~2-hydroxyethyl)amino]ethyl]amino]-i,10-.lihydroxy-2-[2-1(2-hydroxvethyl)amino]ethyl]anthra~
[1,9-cd]pyrazol-6(2H)-one7 ~,lO-dihydroxy-2-[2-L(2-hydroxyethyl)amino]ethyl]-5-I~2-(methylamino)ethyl]amino]anthra[l,9-cd]pyrazol-6(2H)-one;

~æ~ 3~
Cr.G-l -18-2-(2-aminoethyl)-7,10-dihydroxy-5-[[2-[(2-hydroxy-ethyl)amino]ethyl]amino]anthra[l,9-cd]pyrazol-6(2H)-one;
2-(2-aminoethyl)-5-[(2-aminoethyl)amino]-7,10-dihydroxyantnra~l,9-cd]pyrazol-6(2H)-one;
2-[2-aminoethyl)-5-[12-[[2-(dimethylamino)ethyl]-amino]ethyl]amino]-7,10-dihydroxyanthra[l,9-cdl-pyrazol-6(2H)-one;
2-(2-aminoethyl)-5-[[3-[(2-hydroxye~hyl)amino]propyl]-amino]-7,10-dihydroxyanthra[1,9-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-7.-[2-[(2-hydroxyethyl)amino~ethyl]-5-I[2-L(2-hydroxyethyl)amino]e~hyl~amino]anthra[l,9-cd]
pyrazol-6(2H)-one;
7-hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl)-~-[[2-(methylamino)ethyl~amino]anthra[l,9-cd]pyrazol-6(2H)-one;
10-Hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl~-5-[[2-[(2-hydroxyethyl)amino]ethyl]aminG]anthra[1,9-cd]pyrazol-6(2H)-one;
7,8,10-trihydroxy-2-[2-[(2-hydroxethyl)amino]ethyl]-5-[[2-[(2-hydroxyethyl)amino~ethyl]amino]anthra-~~l,9-cd]pyrazol-6(2H)-one;
7,8,10-trihydroxy-2-[2-[(2-hydroxyethyl)amino)]ethyl]-5-[[2-(methylamino)ethyl]amino]anthra[l,9-cd]pyra2O1-6(2H~-one;
5-[[2-~(2-aminoethyl)amino3ethyl]amino]-7,10-dihydroxy-2-~2-hYdroxyethyl)anthra[l,9-cd]pyrazol-6(2H)-one;
2-(3-aminopropyl)-7,10-dihydroxy-5-[[Z-[(2-hydroxy-ethyl)amino]ethyl]amino]anthra[l,9-cd]pyrazol6(2H)-one;
2-(3-aminopropyl)-5-[[2-[[2-(dimethylamino)ethyl~-amino]ethyl]amino]-7,10-dihydroxy anthra[l,9-cd~-pyrazol-6(2H)-one;

3~
CLG-l -19-2-(2-aminoethyl)-7,10-dihydrox~-5-[[2-(methylarnino~-ethyl]amino]anthra[l,9-cd~pyrazol-6(2H)-one;
5-[(2-aminGe~hyl)amino]-2-[3-(dirnethylamino)prop~l]~
7,10-dihydroxyanthra[l,9-cd~pyrazol-6(2H)-one;
7~S-dihydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-[[2-~(2-hydroxyethyl)amino]ethyl]amino]anthra[l,9-cd]-pyrazol-6(2H)-one; and the pharmaceutically acceptable salts thereof.
The in~entlon in its fifth seneric chemical compound aspect is a chemical compound having the structural formula N ~-Z

Q" ~

wherein Q, Q', and Q" may be the same or different and are hydrogen, OH, alkoxy of one to four carbon atoms, chlorine, benzyloxy, p-chlorobenzyloY.y and 2-methoxyben~yloxy; and the pharmaceutically acceptable salts thereof; Z is defined above; and the pharmaceutically 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 as?ect is a chemical compound having the s~ructural formula III
~' Ql o Cl III

~;6~3~
CLG-l -20-wherein Q and Q' may be the same or different and are H, OH, C]_~alkoxy, benzyloxy, p-chlorobenzylo~y, or ~-methoxybenzyloxy and Z is defi.ned above; and the pharmaceutically acceptable salts thereof; provided that ~hen Q = Q' = H9 Z may not be H or CH3~
The invention in a first subgeneric aspect of its sixth chemical compound aspect is a chemical compound having structural for~ula III wherein Q and Ql are H;
and the pharmaceutically acceptable sal.s thereof.
The in~ention in a second subgeneric aspect of its sixth chemical compound aspect is a chemical compound having the structural formula III wherein Q
and Q' are benzyloxy, p-chlorobenzyloxy, or ~-methoxybenzyloxy; and the pharmaseutically acceptable ~alts thereo~O
The invention in a third subgeneric aspect of its sixth chemical compound aspect is a chemical compound having structural formula III wherein Q and Q' are OH;-and the pharmaceutically acceptable salts thereof.
The invention as species of the fifth generic chemical compound aspect of the invention are the ~hemical compounds having the following names:
5-chloro-2-[2-~diethylamino~ethyl]anthra[l,9-cd]-pyrazol-6(2H)-one;
5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]anthra[l,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,9-cd]pyrazol-6(2H)-one;
S-chloro-2--[2-(diethylamino)ethyl]-7,10-~is(phenyl-methoxy)anthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-[2-~[(4-methylphenyl)sulfonyl]oxy]ethyl]-7~10-bis(pnenylmethoxy)anthra[l~9-cd]pyrazol-6(2U.)one;
5-chloro-7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]-ethyl]anthra[l,9-cd]pyrazol 6(2H)-one;

CLG-l -21-5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]-7,10-bis-(phenylmethoxy)ant~hra[l,g-cd]pyrazol-6(2H)-one;
5-chloro-2-[Z-[[2-(dime~hylamino)ethyl]amino]ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
2-(2-aminoethyl)-5-chloroanthra[l,9-cd]pyrazol-6-(2 )-one, 5-chloro-2-~2-(dimethylamino)ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-[3-(diethylamino)-2-hydroxypr 7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-[3-(dimethylamino)propyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-(2-hydroxyethyl)-7,10-bis(phenyl-methoxy)anthra~l,9-cd]pyrazol-6(2H)-one;
5-chloro-7,10~dihydroxy-2-[2-L(2--hydroxyet'nyl)-methylamino]ethyl]anthra[l,9~cd]pyrazol-6(2H)-one;
5-chloro-2-[2-[(2-hydroxyethyl)methylamino]ethyl]
7,10-bis~phenylmetho.yy)anthra[l,9-cd]pyrazol-6~2H)-one;
5-chloro-7,10-dihydroxy-2-[3-[(2-hydrOxyethyli amino]propyl]anthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-[3-[(2-hydroxyethyl)amino]propyl]7,10-~i_,(phenylmethoxy)anthra,;,~-cd]pyraæol-6(2~.)-olle;
S-chloro-2~~3-[[4-methylphenyl)sulfonyl]oxy]-propyl]-7,10-bis(phenylmethoxy)anthra[1,9-cd]pyrazol-6(2H)-one;
S-chloro-2-(3-hydroxypropyl)-7,10-bis(phenyl-methoxy)anthra[l,9-cdJpyrazol-6(2H)-one;
2-(2-aminoethyl)-5-chloro-7,10-dihydroxyan-thra-[l,9-cd]pyrazol-6(2H)-one;
2-(2-aminoethyl)-5-chloro-7,10-bis(phenylmethoxy)-anthra[l,9-cd]pyrazol-6(2H)-Gne;
5-chloro-2-~(2,2-dimethyl-1,3-dioxolan-4-yl)-methyl]-7,10-bis(phenylmethoxy)anthra[1,9-cdl-2YraZol-6(2~)-one;
5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]-7-(phenylmethoxy)anthra[l,9-cd]pyrazol-6(~H)-one;

CLG-l -22-5-chloro-2-~2-[(2-hydrox~ethyl)arnino]ethyl]-10-~phenylmetho%y)anthra[1,9-cd]p~razol 6(2H)-one;
5-chloro-2-[2-[(2-hydro~yethyl)anlino]ethyl]-7,3,10-tris(phen~flmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one;
2-~3-aminopropyl)-5-chloro-7,10-bis(phenylmethoxy)-anthra~l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]-1,8-bis(phenyl~ethoxy)anthra[l,9-cd]pyrazol-6(2H)-one;
5-chloro-2-~2-[[2-(dimethylamino) ethyl]amino]ethyl]-7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2~)-one; and the pharmaceutically acceptable salts thereof.
The invention in its seventh generic chemical compound aspect is a compound having the structural formula IV
N N-Z
[~' NRY O
IV
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 P~l group wherein ~1 is ~I or al.~yl of from one to six carbon atoms/ or A~R2R3 wherein ~ is alkvlene of from two to eisht carbon atoms, R2 and R3 may be the same or diferent and are H, alkyl of from one to six carbon atoms ~Jhich may be substituted with OH or an NRaRa wherein Ra may be the same or dieren~ and is H or alkyl o~ from one to three carbon atoms which may be substituted with OH, or R2 and R3 when taken together may be ethylene or may form CLG-l -23-; ~(CH2)n \

-(CH2)m/
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 s is a direct bond, O, S, or ~I-R4 wherein R4 is H or alkyl of from one to six carbon atoms; R and Y when taXen together may be e~hylene 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 substitut2d with an NtRl)2~ SRl, or ~Rl group ~herein Rl may be the same or different and is defined above, or DNR2R3 wherein D is alkylene o~
rom two to eight carbon atoms which rnay be substituted ~ith an OH group and R2 and R3 are a deined above; and the pharmaceutically acceptable salts thereofi with the following provisos, 1) when 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 do not complete a piperidine ring or a morpholine ring.
The invention as species of the seventh generic chemical compound aspect of khe invention are-the chemical cornpound~ having the following names:
2-[2-(diethylamino)ethyl]-7-[[2-[(2-hydroxyethyl)-amino]ethyl]amino]anthra[l,9-cd]pyrazol-6(2H)-one;
2-[2-(diethylamino)ethyl-7-[[2-(dlethylamino)ethyl]-amino]anthra[l,9-cd]pyrazol-6(2~)-one;
2-~2-~(2-hydro~yethyl)amino]ethyl]-7-[[2-[(2-hydroxyethyl)amino~ethyl]amino]anthra[l,9-cd]pyrazol~
6-~2~)-one; and the pharmaceutically accepta~le salts thereof.

~'æ5~
CLG-l -24-The invention in its eighth generic che~ical compound aspect is a compound having the structural formula VII
N -N-Z
~,X~
Cl O
~II
wherein ~ is defined above, provided it is noc H or CH3.
The invention as a species o. the eighth seneric chemical compound aspect of .he invention is the chemical compound having the following names: ~
7-chloro-2-[2-(diethylamino)ethyl]anthra[l,g-cd]-pyrazol-6(2~)-one;
7-chloro-2-[2-~2-hydrox~ekhyl)amino]ethyl]anthra[l, 9-cd]pyrazol-6(2H)-one; and the pharmaceutically acceptable salts thereof.
The invention in its ninth chemical compound acpect is 5,8-dichloro-1,4,9,10-anthracenetetrone.
The inven~ion 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 for preparing a compound ha~ing the structurâl formula ~ - N-Z
W~
Xl O NRY

which coJnprises reacting a compound haviny the structural formula 3~
CLG-l -25-N ~ Z

' Q"

with an amine having the formula HMRY wherein W, X
X~ Q~ Q~r Ql~ y~ z~ and R are deFined above and, when necessary, removing bv catalytic hydrogenation or by treatment with boron tribromide or trichloride any b~næ~l groups.
The invention in its second generic chemical process aspect is a ~rocess for preparing a compound having struc.ural formula I
N - N-Z

X' o NRY
I

which comprises reacting a compound having structural ormula II

Q N - N-Z

Q' O Cl II

CLG-l -26-with an amine having the formula HNRY wherein X, X', Q, Q', Y, Z, and R are defined above and, when necessary, removing by catal~tic hydrogenation or by treatment with boron tribromide or boron trichloride an~ benzyl 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 su~generic aspect o~ its second chemical process aspect is the process defined above wherein X and X' are Ho The invention in its third generic chemical process aspect is a process for preparing a compound having structural rormula III
N -- N-Z

Q' Cl III
which comprises reacting a compound having formula V
Q O Cl Q~ o Cl V

with a hydrazine having the form~la H2N-NH~, wherein Q, Q' and Z are defined above~

~25~3~
C~G-l -27-The invention in a first subgeneric aspect of i~s third chemical process as?ect is the process defined above wherein Q and Q' are benz~loxy, ~-chlorobenzyloxy, or p-metho~c~benzylo~.
The invention in a second subgeneric aspect oE
its third chemical process aspect i5 the process defined above wherein Q and Q' are OH.
The invention in a third subgeneric aspect of its third chemical process aspect is the process define~
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 formula IV
N - N-Z

NR~ b IV

which comprises reacting a compound having structural ~ormula VII
N - N-Z

Cl O
VII

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

~æs~
CLG-l -28-The invention in its fifth chemical proces~
aspec~ is a process for preparing 5,8-dichloro-1,4,9,10-anthracenetetrone which cornprises reacting ~ dichloro-5,8-dihydroxy-9,10-anthracenedione ~Jith lead tetracetate, The inqention in its sixth chemical process aspect is a process for preparing 2-[(hydrazinoethyl)amino]ethanol ~hich comprises reacting hydrazine with N-(2-hydroxyethyl)aziridine.
The invention in its first pharmaceutical eomposition aspect is a pharmaceutieal composition eomprising a eompound having structural formula I and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier.
The invention in its second pharmaceutieal eomposition aspect is a pharmaceutical compositlon eomprising a compound having s4ructural formula I' and the pharmaceutically acceptable salts thereof in eombination with a pharmaceutically acceptable carrier.
The invention in its third pharmaceutical composition aspect is a pharmaceutical composition comprising a compound having struetural formula I'' and the pharmaeeutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier.
The invention in its ~ourth pharmaceutical eomposition aspect is a pharmaceutical composition comprising a compound having structural ~ormula I"' and the pharmaceutically acceptable salts thereof in combination with a pharmaeeutieally acceptable carrier.

~S~i~3~
CLG-l -29-The int~ention in its fifth pharmaceutical com-position aspect is a pharmaceutical composition com-prising a compound having structural forMula I'''' and the pharmaceu-tically acceptable salts thereo in combinatlon with a pharmaceutically aczeptable carrier.
The invention in its sixth pharmaceutical ^om-position aspect is a pharmaceutical composition com-prising a compound ha~Jing 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 is a pharmaceutical composition com-pri.siny ~ compou,ld having structural formula I'ti and the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier.
The invention in its eighth pharmaceutical-composition aspect is 2 pharmaceutical composition comprising a compound having structural formula IV
and the pharmaceutically acceptable salts thereof in combination wi~h a pharmaceutically acceptable carrier.
The invention in its first pharmaceutical rnethod aspect is â method for treating microbial infections in a mammal which comprises administering a suEficient amount of a compound havinq 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 second pharmaceuti.cal method aspect is a method for treating leukemia in a mammal which COmQrises administering a sufficient amount of a compound having structural .ormula I' and the pharmaceutically acceptable salts thereof in ~5Ei~

combination with a pharmaceutically acceptable 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 thereof.
The invention in its fifth 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 ~ thereof.
~ The invention in its sixth 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 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 ~r, compound having structural formula IViand the pharmaceutically acceptable salts thereof in combination with a pharmaceutically acceptable carrier, to a mammal in need thereof.

~ `

, _ ~5~3~
CLG-l -31-The invention in its eighth pharmaceutical ~.ethod aspect is a method for treating solid tumors in a mammal which comprises administering a sufficient amount of a compound havirlg structural formula L'~
and the pharrnaceutically acceptable salts thereo' in combination with a pharmaceutically acceptable carrier, to a mammal in need thereof.

CLG-l ~32-~ESCRIPTION OF THE PRE:FERRED E~IB(~DI~ENTS
The compounds of the invention may be prepared conveniently by the follo~/irlg reaction sequence Q" ~ ------3~ Q"

V IXI
I

W N- Z ~ _ z W~ C B -- r~

X o NRY X ' O Cl II

The reaction step "A," involves the reaction of ccmpound V and a suitably substituted hydrazine, NH2-N~ wherein Q, Q' and Q'', and Z are defined hereinabove. This reaction may be accomplished in any of a variety o~ reaction inert solvents by rnixing aporoxi;nately equimolar amounts of compound V and the desired hydrazine in the chosen solvent at elevated t~mperature. Use of a catalyst such as potassiurn fluoride or of a slight molar excess of the hydrazine reactant may improve a particular yield. Examples of sultable solvents are N,~-dimethylformamide, dimethylsulfoxide, ~yridine, acetonitrile, the cellosolv~s, and the li~e. Pyridine is the preferred solvent, suitable reaction te:nperatures are from aoout CLG-l ~33~
3~-85C. In general, the reaction is allowed to proceed fo-r about six to about 24 hours at ,lhich time the reaction i5 substantia].ly complete. The completeness of a particular reaction may be measured by ~nown procedures such as thin layer chromatography for ex2mple. It is generally observed that increasin~
the reaction temperature will decrease the time necessary for completing the reaction. The proper choice of the reaction variables is ~ithin the s~ill of the art. The products of the reaction are isolated and purified by standard procedures. For exam21e, the reaction mixture may be concentrated by evaporating the solvent and the residue may be partitioned bet-~een water and a convenient nonwater-miscibl2 organic solvent sucn as chlorororm~ benzene, dichloromethane~
and the like. The solvent may then be evaporated and the residue may be chromatographed, for example, on silica gel. Cholce of the proper chromatog~aphy solvent is within the skill of the art~ After -chromatography, the product may be recrystallized, if desired. ~hen ~he Q, Ql, and Ql- substituents of the so produced co~pound III comprise benzyloxy, p-chloroben~yloxy, or ~-methoxybenzyloxy, the benzyl substituents may be removed, for example, by treatment with ~oron trichloride or boron tribromide in a chlorinated hydrocarbon solvent such as dichloromethane at about 0C to produce compound II
wherein the corresponding X substi~uents represent h~droxyl. Acid addition salts may also be prepared by standard procedures. For example, a hydrochlo~ide 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-?ropanol. The acid addition salts may be reconverted to the respective ~ree base by treatment with a dilute solution of sodium hydroxide or potassium carbonate for example.

CLG-l ~34~
The reaction step "B" involves the reaction of compound II with a suitahl~ subs~ituted amine ~5NR'~
wherein ~, W, X, X', Y~ and Z are deeined hereinabove.
This reaction may be accomplished in any of a variety oE reaction inert solvents by mixing approximately equimolar amounts oE compound II and the desired amine in the chosen solvent at elevated temperature. The use of a slight molar excess Oe the amine reactant, an inert atmosphere and a catalyst such as anhydrcus cuprous chloride may improve a particular yieid. The use of these variations for a particular reaction is optional and is within the skill of the art. ~xamples of suitable solvents are ~I,N'-dimethylEormamide, dimethylsulfoxide, pyridine, acetonitrile, the cellosolves J and the like. Suitable reaction te~peratures are erom aoou~ 85-130C. This reaction has been observed to proceed particularly e~Eiciently in refiuxlng pyridlne. I~ generalj the reaction is - - ~-allowed to proceed for about 6 to-about 24 hours at which time i~ is substantially complete. The completeness of a particular reaction may be meacured by known procedures such as thin layer chromatography or example~ It is general~y observed that increasing the reaction temperature will decrease the time necessary for completing the reaction. The proper choice of the reaction variables is within the skill of the art. The products of the reaction are isolated and ourified by standard procedures which are substantially identical to those described above Lor compound II. Likewise, acid addition salts oE
compound I may be prepared by standard procedures such as that described hereinabove for compound II.
Alternatively, the compound o~ formula III may be treated directly with an amine oE eormula HNRY to produce a compound of the Eormula CLG-l ~35-a~ N~

Q"~
Q' b ~RY

This compound may then be debenzylated by a standard procedure to produce the corresponding compound having structural formula I.
In an alternate process the compounds of formula I wh2re~rl ~ and X' are hydroxy may be prepared by the reaction of compound VI (compound V wherein Q and Q' are dihydroxy O~ O Cl .
¢~
OH O Cl VI

with a suitably substituted hydrazine ~IH2-N~ to proauce a compound of structural formula II wherein is OH; ~ is defined hereinabove~ The reaction of VI
~nd the hydrazine may be accornplished by ~i~ing approximately equimolar amounts of the reactants in a solvent such as ~,N-dimethylormamide, dimethylsulfoxide, pyridine, and the like at temperatures about 30-90C~ preferably 30-60~C, in the presence of a base such as potassium bicarbonate.
Pyridine is the preferred solvent and when utilixed does not require an additional base. The use of catalyst such as potassium fluoride may improve ~56~
CLG-l -36-~he yieId of a particular reaction~ The subsequent conversion of the so produced comoound II ~1herein X and X' are hydro~y to the corresponding compound I
is carried out as already described hereinabove 2S
reaction step "B".
In an alternate method for prepa.ing the compounds of ~ormula III, a compound of formula V is reacted ~ith a hydroxyalkylhydrazine of tne formula N~2-NH(Ca2)2_11-OH, preferably NH2-Na(C~2)2_3-O~
to produce a compound of -Eormula III wherein 3 is -(CH2)2~ ~ and is pre.erably -(CH2)2_3-OH.
This reaction is carried out substantially as described hereinabove as reaction step "An. The OH
grou~ of the Z su~stituent is then derivatized to produce an easily displaceable substituent known to those skilled in the art as a "leaving group". For example, the O~ group may be converted to a tosyloxy or mesyloxy group by reaction with respectively -p-toluenesulphonylchloride or methanesulphonylchloride --in pyridine by procedures known to those skilled in the art. The leaving group, so produced, may be subseauently displaced with, for example, an amine such as diethylamine to produce a Z substituent of the structure -~C~2)2_11-NEt2. In the preferred procedure the substituent Z so produced is -(CH2)2_3NEt2. The benzyl groups or substituted benzyl grou?s of compound III, if present, arè removed as described above ~o produce a compound of formula II, which may be converted to a compound of formula I
as already described hereinabove as reaction step "B".
The compounds having structural formula I ~herein X and X' are chloro are prepared starting from compound VI by first converting VI to the corresponding di-p-toluenesulfonic acid ester VI'.

C~G-l ~37-Cl O OTos ~3 Cl O OTos ~JI' ~ his conversion is conveniently carried out by treating VI with p-toluenesulfonyl chloride in a nonreactive solvent such as acetonitrile at reflux temperature. The diester VII is then treated with a substituted hydrazine NH2N~Z su~stantially âS
described above for the conversion of co~pound V to compound III. The product of this reaction, VI'' N - N-Z
~3 ..
Cl O OTos VI"

is then treated with an amine having the formula HNYR
subs~antially as described above for the conversion of compound II to compound I. The product of this reaction ha~ the following structural formula.

Cl ~ N-z ~3 Cl o NRY
wnerein R, Y, and Z are as defined hereinabove.

The compounds having s-tructural formula IV are prepared by reacting a compound having structural formula VII with an amine having the formula HNRY using substantially the same reaction conditions described above for the conver~ion of compound II to compound I, i.e., reaction step "B".
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 structural formula VII are prepared by reacting a suitably substituted hydrazine, NH2-NHZ, wherein Z is defined hereinabove, with l,5-dichloro-9,10-anthracenedione in a manner substantially identical to that described above for converting compound ~T to compound III, i.e., reaction sequence "~".
The present invention also contemplates the novel hydrazine, 2-[(hydrazinoethyl)amino]ethanol, NH2NHCH2CH2NHCH2CH2OH. 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 N-(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 120C 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. ~or purposes of the invention, such salts are considered equivalent to the free base form of the novel hydrazine.

~25~;~3~

The benzylated ethers V wherein any oE the Q
substituents represent benzyloxy, p-chlorobenzyloxy, or p-methoxybenzyloxy may be prepared by treating compound ~l 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-1,4,9,10-anthracenetetrone may be prepared by oxidation of 5,8-dichloro-1,4-dihydroxy-9,10-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 J. Am. Chem. Soc., 48; 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 ~:5f6~3~
CLG-l -40-equivzlent amount of the desired acid in the conventional manner. The free base forms may be regenerated by treating the salt form with a hase.
For example, dilute a~ueous base solutions may be utilized. Dilute aqueous sodium hydroxide, potassium carbonate, a~monia, and sodlum bicarbonate solutions are suitable for this purpose. The free base forms differ from their respective salt forms somewhat in certain physical properties 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 exis~ in un-solvated as well as solvated forms, including hydrated forms~ ~n general, the solvated forms, with pharmaceutically acceptable solvents such as water, ethanol and the like are equivalent to the unsolvated forms for purposes of the invention~
The term halogen is intended to include fluorine, chlorine, bromine, and iodine.
The alkyl and al~oxy groups contemplated by the invention, unless specified otherwise, comprise both straight an~ branched carbon chairs of from one to about six carbon atoms. Representative of such groups are methyl, ethyl, isopropyl, butyl, pen~yl, 3-me~hyl-pentyl, methoxy, ethoxy~ i-propoxy, t-butoxy, n-hexoxy, 3-methylpentoxy, and the liXe7 The alkylene groups contemplated by the inven-tion, unless specified otherwise, comprise both straight and branched carbon chains of from two to about 11 carbon atoms. Representative of sucn groups are ethylene, npropylene, n-butylene, n-heptalene, ~-propylene, 3-ethyl-1,5-pentalene, 3-propyl~
1,6-hexalene, and the like. The preferred alkylene ~roups of the invention have the following structural formulas:

CLG~l -41-1 l~3 CH3 C~I3 CH3 C2H5 -(CH2)-2~11; -CH-CH2-; -CH2-CH-; - CH - CH-; ~CH-CH2-, C2EI5 l~3 C~3 C~3 - ca-; -C~!-CH2-C~2-; -C~2~C~ CH2 ~ 2 2 Certain substituents, such as alkyl or alkylene substituents contemplated by the invention are defined as possibly being substituted with additional substituents, e.g., NH2. Those s~illed in the art will recosnize that certain combinations of such substituents are Inos~ probably unstable and these are no~ intended to be included within the scope of the defini~ions~ For example~ an ~amlnoal~yl or al'.~ylene group of the general ~or~ula = N-CH~NHz would not be expected to be stable whereas the corresponding dialkylated substituent - N~CH-N~Alk)2 is expected to be stable and is intended to be included within the definitionsO 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 chemlcal substances of value as pharmacological agents for the treatment of bacterial and fungal infections in warm-blooded animals. They ~,ay also be utilized as antiseptic agents such as for use in the steriliza~ion of la'oora'cory glassware etc, The antibacterial and antifungal activity o~ represeptative co~pounds of the invention was es~ablished by the screening procedure described belowO

~25;~3~
CLG-l ~42-1. Pre~aration of inocula _ ~A) Bacteria and yeast-The bacterial and yeast isolates are maintained in agar slants or in liquid media, hereby designated as inoculum media~ The cultures are transferred at regular intQrvals in such media. (See Table for the correspon-ding inoculum media o~ each culture.) The organisms are generally transferred or. to agar slants or liquid inoculu~ media and incubated overnight (18-~0 hours~: 37C for the bacterial isolates and 28C for the fungal cultures.
The microbial cells rrom the overnisht agar slants are then scraped off and suspended in saline solution (0.85% NaCl). The microbial concentrations are adjusted to a light transmittancy of 20-35~, Junior Coleman Spectrophotometer-(555 M ). For the organisms that are maintained in liquid media, an aliquot of the culture suspension is simply diluted with saline to 20-35% light transmittancy.
The above microbial suspension serve as in-ocula for the assay plates. Thus, 0.16-10 ml (see Table for exact amount) are used to inoculate 100 ml of the ~olten-agar assay medium.
(B) Mycelial fungi:
The Penicillium avellaneum is grown for six days, at 28C, on an agar medium. ~his is to allow sporulation of the culture. The organism is then harvested by scraping of~
the cells from the agar surface (mycelia and spores) and suspending them in saline solution con'aining 0.05% Tween* 80.

*trade mark ~5~3~L
CLG-l -43-The suspension is adjusted to a light trans-mitancy of 20~. One ml of this suspension is used to inoculate 100 ml of the mo]t~n-ayar assay mediu~.
2. Preparation of assa~_~lates Stainless steel Crames, 12.3 x 25.3 cm (I~) 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% agarO Twenky five ml of inoculated assay medium is spread evenly on each tray and allo~ed to solidify. The trays are covered, inverted, and refrigerated until used.
3. Diskinq of sam21es 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 is <10%.* The compounds are tested at different concentrations:
3,000; 1,000; 500; 100; and 10 mcg/ml. Paper discs tl2.7 m~ diameter) are placed on the agar ~rays with forceps, then 0.08 ml o~ the dissolved compound is pipetted onto each disc using a 0.2 ml pipette~ (*If the compound does not stay ln solution at <10% alcohol, then the fuli strength alcohol is used. However~ the im2regnate~ discs are air dried before they are iaid on to the seeded agar plates.)

4 Interpretation of results .

The disked agar trays are incubated overnight (18-20 hours) at 37C for the bacterial cultures and 28C for the y~asts. The Penicil]ium avelianeium tray is incubated for at least 20-24 ~S~i~3~
C1G-1 ~44~
hours since it is a slower growing organism.
Acti~e compounds show a zone of inhibition arounZ
the disc. The diameter of the zone is measured in mm~ The zone diameter o~ active compounds 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 the compound: the larger the zone the sreater the zctivity.

~2S6~3~
CLG-l -45-~z L ~

1~` ~ ~ o ~ ~
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CLG-l ~46

5. Culture media The composi~ioll of the various culture media, except for the commercially available media, are sho-.~n below. The commercial ready-made Veal Inusion Medium is obtained from Difco Laboratories, D~troit, Michigan, USA~ Add 1.5%
agar to these media for use as agar plates.
AM-08 %
. . _ Glucose 0.2 Sodium Glutamate 1.04 K~2P0~ 0003 Na2HP04 0.07 Salts ~la 1 ml Salts ~2~ 10 ml H20 (distilled) aSalts ~ 1 % bSalts ~ 2 %
... .. ..

MgS0~ 1.0 MnS0~ 1 0 CaC12 5.0 znSO4-7H20 1.0 NaCl 5.0 FeS04.7H20 1.0 CuS04-5~20 0.01 ~2 Idistilled) H20 (distilled) ~2S~
CLG-l -47-A.~-09 R2HPO4 3~9 gm Dextrose 25 y~
Wa-citrate ~2 H2O 34,4 gm Casein hydrolysate 6~2 gm Asparagine 375 mg L-tryptophan 125 mg Cysteine 312~5 mg Glutathione 3,1 mg Thiamine HCl 25G g Ribo1avin 625 g Ca antothenate 500 g Nicotinic acid 500 g ~-aminobenzoic acid 625 g Bio~in 12~5 g Pyridoxine HCl 2.5 g Folic Acid 500 9 NaCl .12.5 g MgSO4 250 g FeSO4 12.5 g MnSO4 H2O 125 g Tween 80 62.5 mg ~2 (distilled) lO00 ml AM-25 %
Na2HPO4'~2O
~2PO4 0-05 Yeast Extract ~Difco) 0.5 Dextro~e l.0 Distilled Water Utiliziny the above described procedure, the following results were obtained for representative compounds of the invention.

S~D~3~

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C~G-l ~57~
~ n addltion to their use4alness as an~ibio~ic znd antifungal agents, cer~ain o.' the comsounds o the in-ven~ion displav in ViYo antileukemic activity when tested by the followinq proced~re.
The in ~ivo lymohocy~ic leukemia P398 test is carried out by the ~nited States Mational Cancer TnstituteO Th~ ani~.als used ar~ eitA2r m2le or ~emale Fl mics~ There are six to seven animals ,?er te~s~
groupO The tumor trar.splan~ i5 ~y Lntraperi~oneal injection o~ dilu~ ascitic fluid contalning cells of lym~hocyti~ ~eukemia P388. The ~es compounds.are ~d~iniste~d intrap~ritoneally in ~wo single doses wit~ a ~our~da~ int~rval be~een dos2s at vario~s dos~
levels following tumor inocula~lo~. The animals are weighed and survivors are recorded on a regulzr basis for 30 day~. A ratio o~ survival ~ime 'or treated (T)/control ~C) animals ~s calculated. ~he c~i~erion for efficacy is T/C X 100 > 125%. T~.e.positive . .~.
control com~ound in ~his test is l,4-dihydroxy-5,8-[bis~[2-C~2-hydroxye~hyl)amino]~ethyl]amino]-9,10-anthracer.edione given a~ dosages ranging 'rom 12.0 to 0.075 mg/~g. See Czncef Che~otheraDY ~eports, Part 3, 3, 1 (1972) for a co~prehen~ive discussion of the protocol~
Utilizing tnis procedure, the ~olLowi nq res~l ts were ob~ained for representa~ive compounds oO~ th~ , invention.
N - M-Z

X~

13~L
CLG-! -58-X ¦ ~ ¦ N~
... __ I . _ Im~/k~ I (7O~cent) 7~10 (~32 (CH2)2N(-~e)2!~H(c~2)2Nd(cd2)2oHl 12.5 1242, 162 I ~ I 0.781161 7,10 ( CH ) 2 ! ( C H2) 2N ( ~e ) 2 ¦ ~H ( C d 2) 2 NH 2 6 25 ¦ 216, 192 ( H)2¦(CH2)2N(Et)2¦~H(CH2)2~(Et)2 11 118 174 .2Hcl I i 25 1140, 143, 149 12.5 1132, 114, 140 (CH2)2r (t)2lNH(cH2)2NicH2)2]2ol2ooo 1l2~o l4a I l lO0 l 145, 126 Hl(cH2)2N(Et)2l~H(cH2)2N~l(cH2)2 ¦ 12 5 ¦161, 152 178

6,25l145, 146 161, 17a 3.121128, 142, 164, 151 1.561142, 142 146 ~2~J~
CLG-l -;9-X ¦ 3 ! tlR'~ I Dos ~ r/C X 100

7~lo-(oH!2l (CH2 )2~;Et)2 ¦'iH(C~12)2 JH(Cr~2 )2OH¦ 12.5 ¦Z64, 212 6.251 180,180, 164 2HC1 1 13.121164,154, 166 1.56114a,L49, lS;
10,781140,151, lC9 .391 152 126 7,10-(OH)2 11~H2)2N(Et)2 1~H(C~2~2.1H~e ¦ 2S I L72 2HBr I 112.S 1191 6.251 163 3.121154 7,10-(OH)2~(C.'1~)2N(Et)~, H(CH2)2NH2 25 L79 Cures 12.5 280, 189 Cures 2i~C1 1 16.251189,191 3.121154, 160 1.561 172 21 2)2 (C2)2N(.`~e)21NH(C~2)2N8(CH2)2OHI S0 1226 12. S 1179,219 6.251 198,191 3.121207 7,10-~OH)2¦(CN2)2 ~s(cH2)20H It1CH3(C~'12)2N~?4e)2 ¦ 6:2sll7s 2HCl I l l 7,10-(OH)7¦(-H2)2NH(CH2)2OH ¦N~(CHz)212:1Me I L2.5 ¦L69 1 21!C1 ~ 16.251163 H ¦ ~Cg2 ) 2NH ~C~2) zOHI NH ( CH2 ) 2N (Me ) 2 ¦ 25 I L62 2HC1 1 ¦6.251163, 174 - I I I3.121 158 _ ~.~S6~
CLG--' _~ ____ X ¦ 2 ¦ NRYI ~ose 1 ~/C X 100 m~/Xq I I ?er-ent 7,10-~OH),i(CHz~2r~;~(CH2)2OHlNH(c~2)2~ e)2 ¦ 25 1 8a Cures 12.5 1220, 250 Cures 1 2EIC1 1 1 6.251165 la2 3.121165 165 1. 561161, 165 0.7811;2 Hl ~c82)2NH(cH2)2oHlN8(cH2)2`l(Et)2 ¦ 25 11~9 I L2.5 llS0 lS; 15a, lS0 2HC1 1 1 6.251138 146 lS0 142 3.121 143, 143, 14~ lSl 1.56 l 138, 133 7,10--~0~)2 j~CH2~2NH~C~2)20H¦NH~C~2)2~Et)2 ¦ Sû 1241 125 1190 209 Curss 2HC1 1 112.5 1177; 190 6.251 154 16a 3.121 148 lS0 11.561131, 135 7~1~ (0H~2l~tu2)2NH~cil2)2oHlNH~cH2)2N8(cH2)%N(l~e)2i 50 1200, 254 Cures 125 120~, 228, 12 2~1Cl l lI Cur2q 12.5 1157, 179, la8 16.251169, 172 3.121 152, 163 ~¦ ~CH2)2NH(C~2 ),~¦ ~i8 ICH2)2NH(CH2)2O~} ¦ So ¦ 199 125 1171 185, 185 CR3CO2R I 1 12.5 1148 189, 166 6.251147, 157, 166 3.121138 lS0, 166 I _ 1 1. 561132 142 3~
CLG-l ~o l -r ~ S/~ I (?~rcent) 7,10-(OH)2~ }2)2;i~i(c~z~2otilNH(ci2)z' i1(c~2)2o ¦ l ~2HC1 1 1 12.5 1153, 177 6.251206 Cur~s 3.121107, 187 I I I l . Sfj I lSa, 16a H¦ (cH2)2tia(c~z)2o~iNH(cH2)2~;fl2 ¦ 12.5 jl75, 1S30 I ZHCl ll I 1 561150 7,l3-tOH~2l(CB2)2N~(c~2)10Hl~H(c~2)2~lH2 1 3 12¦15i3, 196 Cures ! 2HC1 1 1 0 7S3l1a2 7~lo - ~oH)2l(cH2)2N~(cH7)2odl~H(cH2)3tlH(~-Rt)2oHl 6 251169 254 Cure~
1 ~2RC1 ¦ 1 1.561201, 167 7~lo-(oH)2t(cH2)2NH(c~2)2oHl~H(cH2)3NH2 1100 jl31 Cures 1 ~2HCl I 1 25 1207 250 Cures 12.5 1177 190 ' I 6.25 l 165, 172 l l 1 3.121165, 165 7~10 - (O~)2l(CR2)2NH(CH2)20H¦NH(C~2)4N 2 1 25 llS0 152 1~.5 1139 14;
6.251131 I I I ~.1211~0 7,10--(0H~2¦(CH2)2Nfl(CH2)20H¦NH(CH2)5NH2 ¦100 ¦1SO
S0 127, 139 2HC1 1 1 12,5 ¦127 C.G-I -62 -X ¦ ~ ¦ NllY I DOf~Q ¦ -/C X 100 ~ q/kq I ~ r c~ r t ) _ gl (Cq2)2;~H2 1:`lH(cH2)2~H(c~2)2oHl 12 5 ¦173~ 177 3.121 1~9, 158 1 1.561139 7,10-(Qa) j(-H ) ::H ¦ ¦ 12.5 ¦182 1. 561 153 7 lo-~C~ "H ) Ole ¦ ~ 50 ¦135 12. 5 1 127 7~10--(9H~2¦~c~2)2oH ¦~H(Ca2)2N~He)2 ¦100 ¦225 242 ~ I I S0 1 180, 182, 182 1 29 ! L53, 157, 173 1 12.5 1124, 135, li9 7 ~ 10--( O H ) 21 ~ C H 2 ) zOH I 1 2 0 0 1 16 7 37.5 1135 1 25 112a 7,10--(0g)2¦(C12)2Oa ¦NH(CH2)2NH(CH2)20H¦200 1196, 271 gCl I î 50 1163 155 1 165, 187 12.5 1158, 163 6.251143, 163 7 _ rl R Y
I rr;~kq I ~ P g r e ~ n ~ ) 7 10-(OH~2~ 2~ZOr! I (CH2)Z~B2 11OO l172, Lg6 I .2HC1 I S~ 1162 L72 1 12 5 l145 l51 I I 1 6 25l135 7 10~(OH12I(~H2)2~e 1 ( 2)2 (C 2)20H I 126 25l1L4302 7,10-I~H)ZtC92CHOHCB2N(Et)2 INH(CH2)2N(Et)2 l100 ¦157 I .2HC1 1 1 50 131 135 1 12.5 l128 21 2 0 C~2~(Et)2 ¦!la(CH2)2NH(CH2)20a 1 12 ~ ¦132 223 Cures I ! 3.12l129, 188, la9 I I 1 1.56l139 1 0.781132 7 1O-IOH)2ICH2CHOHCH2~(Et)2 ¦NH(CE2)2NH2 1 12.5 t142, 213 I .2HC1 6.ZS 16O, 189, I 1 1262 CUre5 1 1.5ollS7~ 1~;6 ( 0 . 7a ( 132, 179 I 1 0 39l135 7,10-(OH)2lMe ¦NH(CB2)2NH(CB2)20H 11OO ¦174 j I 1 25 ILSO~ 164 1 12.5 l140, 149 I 1 6.25l133, 1;5 i I 1 3 12l138 7 10-(0H)2l CB2CH2NH2 ¦NHCB2CB2NH2 1 25 l156, 218 1 12.5 l144 203, 221 7,10-(OH)2¦ C92CB2NMe2 1 2 2CH2Na2 1 12.5 l205, 208 1 6 25l196 Cures 7~1O-(OH)2ICB2CB2CH2 2 INHCH2CH2NHCa2CH20H I 12 5 ~218 203 1 6.25l185,167 7 1O-(OB)2IC~2CH(O~)CB2OB¦NaCH2CH2NHCH2CH2OH l400 l281, 255 I200 ;218, 213 ¦ .2aC1 ¦~HCB2CH2CH2Na2 1 12.5 1173 180 j ~ 6.25l167,173, 190 7~1O-(O8~2ICH2CII2CH2~Me2 ¦NHCH2CH2NH2 i 12 5 1224 Cure~
I I 1 3 12l191, lao ,~0-(OH)2¦CB2CH~NMeCH2CH20H ¦NHCH2CH2NHCB2CH20H 1 12.5 l203 .1 6HC1 1 1 6.25I182 I 1 3 12l184 ( ~2!CH2CH2NHCH2CB2OH ¦NH(C92~3 (CH2CH2OH)2I1OO l192 I I 1 25 l163 (OH)2 CB2CH2NHCH2CH20H INHCH2CH2~HCH2CH2NH2 1 25 l221, 227 Cure9 ~ j 12 5 1233 231 CUre9 -S4- 3~ 5~i~3:~

C~

~t ~ 7 ¦ ~RY I Gose ¦ ' iC X 100 I r;w/ ~ s I ~ 7g r ~C e n 1: ) ( H)2 IC:{2cH2NHcH2~H2(7H jNHCH2~H2!J(CH2CH20H)2 1100 ¦223, 254 2.3HC1 1 1 50 1203, 169 25 ,1a7, L94 12.5 I1;a, 156 )2 ~ 2cH2~yHcH2cH2oH ¦NH(cH2)3~yd(cH2)4NH(cH2)3Nii2l 12-5 I145, 117 2. 75HCl I I 6.25 ! 127, 109 7~10-~OH)7 ¦(C~2)3~HCH,_H20H ¦NHCH2CH2NHCH2CH20H I100 ¦2sg Cur?s 1222, 183 I1a3, 174 I 12.5 ILS7, 146 '(OH)2 j (CH2)3t;HcH2cH2oH jNdcH2c:{2c'!2Nii2 I100 I185, 155 O.lHC7 I I SO I160, 146 (OH)2 ¦C'12CH2NHCH2CH20H jNacH2cH2NHcH3 1 12.5 I277, 275 Cures CH3C02H-H3r ~ I6.25¦277, 275 Curcs 3.121268, 177 CJres 7,10--(OH)2 ¦ca7CH2~H2 ¦NHcH2cH2~yHcH2cH2NMe2 ¦ SO ¦ 220 Cùres 3.3HC1 1 1 25 1192 177 12. 5 I1B6 157 7,10--(OH)2 ¦CazCH2NH7 1 2 2 2 CH2cH2oH I 6.25I1a4, L94 2.1HCl I 1 3.121 L77, 134 I ~L.561131, 172 7,lO-(OH~2 ¦ca2c~d2cH2NH2 ¦NHCH2CH2YHC-Y2CH20H ¦ SO ¦285 Cures 2HC1 1 1 25 I285 Cur?s 1 12.5 I247, 163 Cures _ __~ _ I I 6.25I193, 134 7,1O_~OH)2 ¦Ca2cH2c 2 2 ¦NHCH2CH2NHCH2CH2YMe2 ¦ 25 I223 L30 7,10--(Oil)2 ¦Ca2CH2 3 ¦NEiCH2C92RHCa2CH2oH I 12.5 I147 7-OH ¦Cd2Ca2NHCH2CH20H ¦NHCH2CH2NHCH2CH2GH I 25 I285, 184 Cures 2aU I 1 12.5 I228, 142 ures 6.ZSI 133, 134 10-oti ICH2cn2NHcH2cH2H INHCH2cH2NHcH2cH2H lloo ¦221, 184 2.1HCl I 1 50 I172, 16i I 25 I163, lSS

7~8~10-(OH)3tCH2CH2~IHCH2CH2Gl; IYHCH2C'd2!iHCH2CH20H ¦ 25 I265 Cuces 2.1HC1 I 1 12.5 1257 Cures 7~9~i--~:~H~3IcH2cH2NHcH2cH20H INHcH2cH2NticH2cH2oH I 3.121165 2.1HCl I I 1.561155 Cl,G-l -55-,, ~_ O Z ~ O ___ _ __ _ ______ ~ X _ ~- ~ o C~ o .~__ _.__________ ~o.

E _ _ Broad ~ectrum Ant1~mor Activit~ oF 2-¦2-(D1eth~L-a:~lno)erhv' 1-7,10-dihYdrox~ 12-1(2-h~drox~ t'~
a~L~0¦2 ~lla ! - ~ -[ L~

HO N ~-N (Ca2) 2N (Et) 2 2i~C1 OH d NH(ca2)zNEi(ca2)2oH

Tumor ITumor/l~egi~enl Dose I~C x 100) ~ Tumor .. .. - . !Dru~ g/kg)i~2e~cent)l~eduction ADJ-PC5 P'as~7acytoma IIP/IPIQO4DXO3l 16 1 163 I l 1 8 1235 ~ Z16 al6 :~elanoma ~3DF1) IIP/IP lOO1DXO9I 3 ¦ 176 ai6 ~leLanoma IIP/IP ¦Q01Dx091 6 1 189 (36C~'l) I I 1 3 11~1a Co1Orl 3a taDpl) ¦SC/IP IQO1DXO9¦ 16 l l 71 L1210 Leulcemia(C3F1)lIP/IP IQOIDXO9l 16 1 133 l l 1 1 1137 M5075 Ovary IIP/IP IQO4DXO4¦ 10 1 260 1 2.5 1 233 1.251 143 ~Proc~ure described in Cancer Chemotherapy Reviews, 7 167 (1930) and reference.~ cited therein.

~ZS6~

CLG-l -67-In addi~i~n ~o ~eir usefulness as anti~iotic and anti.ur.gal agen~s and as antileukemic agents, cer~ain of the comoounds o~ ~e invention display in vitro activity aqair.s soli tumors when tested by ~he ollowing procedure, ~ C~8 (human colon adenocarcinoma) cellc ar~
trypsini2ed using Trypsin-E~T.~, ~ sinql~ c~ll sus~ension is ac~iev2d by ~assing the cells throuqh a 2S ~ausc needle ~ih a 20 cc syringe. ~ cell suspension is prepared using RP~I 1640 grow;A medlum (availabl~ ero1~ Gibco ~abora~ori~s) + 10~ f~tal calf ~er-um ~ 50 ~g/ml garamycin wi h a cell concentra~,io~
of appro~ima~ely 30,000 cells/~l~ Th~ cell sus~ensicn is dispe~sed in ~inbro 23-well plates; 1 ml/w~lL. T~e ~lates are incub~ted 'or apDroxi~ately 48 hrs at 37C
in a S~ C02 at~osohere, A~ this ~ime tes. compcunds are added in the ap?ropr~ate concent.ation. Five ~1 of the 2C0 ~g~ml stock solution is added t~ .eac~
well in a primary testl Ten ~1 of the zpprooriate dilution is added ~o e~ch well for a titratlon tes~.
The pl2tes are reincubated an additional 60-6~ hrs at 37~C in a 5~ C02 a~osphereO The test is read by lysing the ceLls usin~ a mix of cationic surfactan~c, glacial acetic acid 2nd sodium chloride~ Two ~.1 of the lysed cell su~oension ~rom eac~ well is added ~o

8 ml o~ dlluent. Each sample is read with~a Coulter counte_ ~Z3I ~od21). ~he ac~ivity of e~ch sample i5 measured as a pe.centage of ~he con~rol~ and the da a is reported as IDso, ~hat i5 the molar quanti~y of drug requir2d to kill 50~ of the tumor cells/
U'cilizing ~hi~ procedur2, ~h~ Eollowing re~ults wer~ obcained ~or represen'cative compounds o~ 'cn~
in~en~on~ ' C-~G-l -68-r.. Vitro Activity o~ Aminoanthra?yrazoles Aqainse Ruman Colon Adenocarcino~a N N-Z

X~

X¦ Zs ¦ ~Ys ¦ IDso Molar N¦~CH2)2NEt2 ¦ (CY2)2~Et2 1 1.4 x 10-7 ..
2HCl H¦ CH3 ¦ I ~)2 t2 ¦ 4.1 x 10-7 2HCl l l ¦(C 2)20H INH(CY ) I 1.8 x 10-5 I ,2HCl l l B¦ H ¦Nd(CH2)2NH(CH2)20H¦ 1.5 x 10-6 j ~HCl H¦ CH3 ¦N~(CH2)2NH(CH2)20H¦ S.O % 10-7 I ~YCl l l a¦(CH2)2NEt2 1 ( Y2)2 2 1 5.2 x 10-'3 ~2HCl I I ~
¦( 2)2~H(CH2)20H ¦NY(_R2)2N~(CH2)0H ¦ 9.6 x 10-7 CH3Co2H

CIG-l -69--T~
Xl Z I NRY I ID90 Molar I
HIICH2)~H(CH2)2OHINH(CH2)2NH2 1 ~.2 X 10-8 I .2HC1 HI(CH2)2NH(C~2)2OEINH(CH2)2NEt2 1 1.2 ~ 10-7 I .2HC1 ~¦(C~2)2~H(C~2~20HINH(C~2)2 ~e2 1 2 3 K 10-7 I .2HC1 H¦(CH2)2NH(ca2)20HlNHcH3 ¦ 2.8 K 10-7 I ~IC1 ~I(CH2'2H I (C 2)3NEt2 1 ~.8 X 10-7 I .2HC1 H¦(CH2)2NEt2 ¦NH(CH2)2N~_~O I 1.2 X 10-7 . 2Hcl ~ l H¦ (CH2)2NEt2 ¦ (Ca2)3NEt2 ¦ 1.3 K 10~7 I .2~C1 H¦(CH2)2NEt2 1 ~C 2)~ Et2 1 2 2 X 10-7 I .2HC1 H¦(CH2)2NEt2 1 ( 2)7 t2 ¦ 2 2 X 10-6 H¦(CH2)2NEt2 1 ( 2)2 ~ ~ H ¦ 3.8 x 10-7 3H~r I~C 2)2NH2 ¦NH(CH2)2N~CH2)2OH¦ 6 . 8 x !0 -8 I .2HC1 C~G-l -70-X I ~ I NRY I ID50 ~t~l~r ., I .
,l0-(OH)2~ 2)2rlEe2 ¦NH(C~2)2`~(CH2)20H¦ 2.7 x 10-7 ~2HCl I l 7,10~(OH)2¦(C~12)2NEe2 1 ( 2)2 Et2 ¦ 5.~ x 10-7 1 ~2HCl l l 7,10-~OH)2l CH3 ¦~8(CH2)2r~H(CH2)20H¦ 7.9 x 10-7 .~ICl 7~}0-!oH)2l(cH2)2qEt2 1 ( 2)2 'i2 ¦ 3.3 x ;0-7 2i 2)2 2 ¦NH(cH2)2NH~2 1 1.2 X 10-7 1 ~2HBr 7~lo-!oH)2l ~CH2)2N~e2 ¦NH~CH2)2NH(CH2)20'i¦ l.a x !o-7 1 ~2HCl 7,1d-(OH)2¦ Ca2c~oHc~2~Et2 ¦NH(CH2)2 2 1 4.6 x 10 - 7 I 2HCl 7~10--(OH)2~ C~l2cHoHcsi2~qEt2 INH(CH2)2NH(cH2)2o J 2~1Cl 7~lo-~oH)2l(cH2)2oH ¦NH(CH2)2NMe2 1 1.7 x 10-7 I .I~t:l l I
7-10-(oH)2i(ca2)2N~e2 ¦NH(CH2)2N~i2 ¦ 1.4 X 10-7 I 2HCl 7.10-~oH)2l~c~i2)2NH2 ¦NH(CH2)2NH(CH2)20H¦ 1.7 x 10-6 2HCl I

~s~
C~G-l -71-. _ I
X I Z I N~Y I 1350 ~ola~
7,10-(OH)21(cH2)2NH(c 2)2 ¦ ~ 3 ¦ ;.4 x 10-7 ?,lO-(OH!2¦(CH2)2~H2 ¦ ! 2)2 t2 ¦ 3.1 x 10-7 7HCl 7,10-(OH)2¦(C~2)2~Me2 1 ( 2)3 2 1 i.l x 10-6 I 2tlCl l l 7,10-(OH)2t~CH2)3'~Me2 1 ( 2)3 2 ¦ 3.5 x 10-7 1 ~2HCl I I
7~lo-(ott)2lcH2cH2cH2NM~2 INfiCH2c~2~`~HcH2cH2H I 9-2 x 10-8 I 2HCl 7~lo-(oa)2lcll2cH2~MecH2ra2oHlNHcH2cH2NilcH2cH2oH I ~.5 ~ 10-7 7,10-(OH)2¦CH2CH2lqiiCH2CH2oH jNHCH2CH2NHCH3 ¦ ~.0 x 10-7 I .1.8HCl l I
7'1-(H)2lCU2CII2NH2 ¦NHCH2CH2NHCH2CH2~Me2¦ 1.2 x 10-6 1 ~3.3HC1 ( )2~ 2 2NH2 ¦~H(CH2)3NHCH2CH~H I z.a ~ 10~7 I 2.1HCl 7~lo-(oH)2lcH2cH2Ntt2 ¦~HCt~2CH2CH2Na2 1 3.5 x 10-7 I 2.9HCl 7~lo-(otl)2~cH2cH2cH2~qH2 ¦NtiCH2CH2qHCH2cH2oH ¦ 7.7 x 10-7 7,10-(OH)2¦CH2CH2NttCH3 ¦NHCHzCH2NHCH2C!t2OH j 2.3 x 10-7 1 ~2HC1 1 1 7-OH¦CH2CH2NHCH2cH2oa ¦NHCH~CH2NilCH2CH2oH I 6.1 x 1O-8 1 2NCl O-OH¦CH2CH2NHCH2CR2OH ¦NHCH2CH2NHCH2CH2OH I 1.1 x 1o-6 ~2.1HCl I 2 2 2 2 ¦NHCH2CH2NHM~ I 2.7 x 10-8 1 ~1.8HC1 N--N-Z
'. ~

NRY O
- I
æ INRY ¦ IDso Molar (CH2 ) 2NEt2 ¦NH (CH2 ) 2~Et2 1 2. 2 x 10-7 2HCl ¦ I
2)2NEt2~ NH(C~2)2NH(C~2)2OH ¦ 9.3 x 1o-8 CTJG-l -73-When being utilized as antibiotic and antifung~l agents, the compounds of the invention can be prepared and administered in a wide variety of topical, oral, and parenteral dosage forms. It will be clear to those s~illed in the art that the Lollowing dosage forms m2y comprise as -the actlve component, either a compound of formula I, certain o~ the compounds of formula II or a corresponding pharmaceutically acceptable salt of one of said compounds or a mixture of such compounds and/or salts.
For preparing pharmaceutical compositions from the compounds described by this invention, inert, pharmaceutically 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, flavoring agents, solubilizers, lubricants, suspending agents, binders, or tablet disintegrating agents; it can also be an encapsulating material. In powders, the carri~r is a finely divided solid which is in admixture with the finely divided ac~ive 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 rom 5 or 10 to about 70 percent of the activ.e ingredient. Suitable solid carriers are ma~nesium carbonate, magnesium s~earate, talc, sugar, lactosef pectin, dex.rin, starch, gelatin, tragacanth, methyl cellulose, sodium carboxymethyl cellulose, a low ~elting wax, cocoa butter, and the like. The term "preparation" is intended to include the formulation of the active compound wi~h encapsulating material as carrier providing a capsule in which the active co~.ponent (with or without other carriers) is C~G-l -74-surrounded by carrier, which is thus in association with it. Similarly, cachets are included. 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 may be mentioned water or water-propylene glycol solutions or parenteral injectionO Liquid preparations can also be formulated in solution in aqueous pol~ethylene ylycol solution. Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, 1avors, stabilizing, and thickening agents as desired.
Aqueous suspensions suitable for oral use can be made by dispersing the finely di~ided active component in water with viscous material, i.e., natural or synthetic gums, resins, methyl cellulose, sodium carboxymeth~l cellulose, and o~her 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 r Chapter 43, 14th ed. 1970, ~ack Publishing Co., Easton Pennsylvania 18042, USA.
Preferably, the pharmaceutical preparation is in unit dosage form. In such form, the preparation is subdivlded into unit doses containing appropriate quantities of the active component. The unit dosage form can be a packaged preparation, the package con-taining discrete quantities of preparation, or example, packeted tablets, capsules, and powders in vials or ampoules. The unit dosage form can also be a capsule, cachet, or tablet itself or it can be the appropriate number of any of these packaged form.

~'25~
CLG-l ~75~
The quantity o~ active compound in a unit dose of preparation may be varied or adjusted from 50 rng to 500 mg according to the particular application and the potenc~ of the active ingredient.
In t'nerapeutic use as antibiotic and antifungal agents the compounds utilized in the pharmaceutical method 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 0,5 mg to about 10 mg per Xilogram is preerred, The dosages, however, may be varied depending upon the requirements o the patient, the severity o the condition being treated, and the compound being employed. Determi nation of the proper dosage ~or a particular situation ~ hin the skill of the artq Generally, treatment is initiated with smaller dosages which are less than the optimum dose of the compound. Thereafter, the dosage is increased by small-increments until the~
optimum effect 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 parenterally or intraperitoneally. Solutions of the active compound as a free base or pharmaceutically acceptable salt can be prepared in water suitably mixed with a surfactant such as hydroxypropyl-cellulose. Dispersions can also be prepared in glycerol, liquid polyethylene ~lycols, and mixtures 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 an~ sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases the form must be ste~ile and must be fluid CLG-l -7h-to the extent that easy syringability exists~ It 3 must be stable under the onditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example~ glycerol, propylene glycol, 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 coatinq such as lecithin, by the maintenance of the required particle size in the case of disper-sion and by the use of surfactantsO The prevention of the action of microorganisms can be brought abOut by arious antlbacterial and antifungal agents, ~or 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 gelatin~
Sterile injectable solutions are prepared ky încorporating the active compound in the required amount in the appropriate solvent wi~h various of the other ing~edients enumerated above~ as requirad, ~ollowed by filtered sterilizationO Generally7 dispersions are prepared by incorporating the various sterilized active ingredient into a sterile vehicle which contains the basic dispersion medium and the required other ingredients .rom those enumerated above~ In the case of the sterile powders fo~ the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and the freeze-dryin~ technique which yield a powder of ) the active ingredient plus any additional desired ~5~
CLG-l -77-ingredient from a previously sterile-filtered solution thereof.
As used herein, "pharmaceutically acceptable carrier~ includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like.
The use of such media and agents for pharmaceutlcally active substances is well known in the art. ~xcept insofar as any conventional media or agent 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 ~ormul~te parenteral compositions in dosage unit form or ease of administration and uniformity of dosage. Dosage unit form 2S used herein refers to physically discrete units suitable as unitary dosages for the mammalian subjects to be treated; each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic e~fect in association with the required pharmaceutical carrier. The specification for the novel dosage unit forms of the in~entio~ are dictated by and directly dependent on (a) the uni~ua characteristics of the active material and the particular therapeutic ef ect to be achieved,`and (b) the limitation inherent in the art of compounding such an active material for the ~reatment of disease in living subjects having a diseased condition in which bodily health is impaired as herein disclosed in detail.
The principal active ingredient is compounded or convenient and ef~ective administration in effective amounts with a suitable pharmaceutically-acceptable carrier in dosage unit fcrm as hereirbefore disclosed. A unit dosage form can, for example, -,39L
CLG-l -78-contain the principal active compound in amounts ranging from about 0.1 -to about 500 my, with rom about 0.5 to about 250 mg beiny preEerred. ExprPssed in proportions, the active compound is generally present in from about 0.1 to about 500 mg/ml of carrier. Xn the case of compositions containing supplementary active ingredients, the dosages are determined by reference to the usual dose and the manner Or administration of the said ingredients. The daily parenteral doses for ma~alian subjects to be treated ranges from 0~1 mg/kg to 100 mg/Xg. The preferred daily dosage range is 0.3 mg/kg to 10 mg/Xg.
The following nonlimiting examples illustrate the inventors' 2referred methods for preparing ~he compound~ of the inven~,ion.

~L~S~ 3~
CLG-l ~79~
~XAMPL~ 1 `~ 2-~2-(Diethylamino)eth~_]-5-[_[?-( _ t~ ino)ethyll-amino]anthra[l,9-cd]pyrazol~6(2H)~on~
A mixture of 1.2 g (3 4 mmol) of 5-chloro-2-[2-~die-thylamino)ethyl~allthra[l,9-cd]pyrazol-5(2a3-one~
1.0 g (8 mmol) of N,N-diethylethylenediamiAe, 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 U 5 g (4 mmol~ of the diamine and about l mg of catalyst is added and the mix~ure is refluxed for 23 hours7 cooled, and concentratedD The residue is dissolved in dichloromethane, washed successively with wa'er~
dilute ammonium hydroxide, and brine. Chromatography O F the dried dichloromethane layer over siliGa g21 with 10:1:89 methanol:triethylamine:dichloromethane provides the purified product. Dissolution in hot 2-propanol followed by treatment with excess hydrogen chloride in 2-propanol a'~ords 1.2 g of the dried product as a salt with 2.1 equivalents o~ hydrogen chloride solvated with 1~2 equivalents of water; mp 262-276C (decomposition) 5-Chloro-2-~2-~diethylamino~ethyl]anthra[l,9-cd]-pyrazol-6(2~)-one is prepared as follows:
A mixture of 4.15 g (15 mmol~ of 1,4-dichloro-

9,10-anthracenedione ~J. Amer. Chem. Soc~ 48; 3198 (1926)] 2.6 g (20 mmol) of (2-diethylaminoeth~yl~-hydrazine ~J. Med~ Chem~ 493, (1964)~, and 35 ml of pyridine is heated at reflu~ 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 wi~h ethyl acetate and then 95:5 ethyl acetate:methanol affords 3.8 g o~ a solid whose crystallization from 2-propanol gives 2.9 g of pure material; mp 90-92C.

CLG-l -80-Dissolution of 0.89 g of the product in hot 2-propanol followed by treatment with excess hydrogen chloride in 2-~ropanol affords O.9 g of the hydrochloride salt; mp 263-266C (decomposition).

2-[2-(Diethylamino)ethyl)]-5-[~2-[(2-hydroxyethyl) amino]e~hyl]amino]anthra[l,9-cd]~yrazol-6(2H)-one A mixture of 2.5 g (7.1 mmol) of 5-chloro-2-[2-(diethylamino)ethyl]anthra[l,9-cd]pyrazol-6(2H)-one, 1 g t9 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 re~lux under argon. Addi~ional 0.5-1~0 g portions o~ the amine and catalytic amounts oE the halide salts are added after six and 12 hoursl respectively. After a total reflux time of 30 hours, - the mixture is worked up as descri~ed for Example- 1, - -with purification on silica gel utilizing first

10:1:89 and then 15:1:84 methanol:triethylamine:ethyl acetate. Following treatment with hydrogen chloride, ~here is obtained 1.1 g of the dried proZuct as a salt with 2.0 equivalents of hydrogen chloride solvated with 2.4 equivalents of water; mp 239-241C
(decomposition).
EX~MPLE 3 5-~(2-Amino~th~l)aminoJ-2-[2-(diethyl2mino)ethyl]-anthra~l,9-cd~pvrazol-6(2H)-one A mixture of 1.6 g (4,5 ~mol) of 5~chloro-2-[2-(die~hylamino)ethyl]ar.thra[l,9-cd]pyrazol-6(2Hj-one, 2.5 ml of anhydrous ethylenediarnine, and 25 ml of anhydrous pyridine is heated at reflux under argon for seven hours, cooled, diluted with toluene, and concentrated. The solid residue i5 dissolved in dichloro.~ethane, washed with water, ~nd then brine.
Chromatography of the dried dichloromethane layer over silica gel with 1:9 ~ethanol:dichloromethane provides , ~l25~
CLG-l -81-0.8 g of the product. Dissolution in hot 2-propanol follo~ed by treatment with excess hydrogen chloride in 2-propanol affords 1.0 g of ~ried product as a salt with 2.0 equivalent.s o~ 'nydrogsn chloride sol~ated with 1.8 equivalents of water; mp 276~279C
(decomposition).
The following compounds are prepared as described in Exzmple 3 from 5-chloro-2-[2-(diethylamino)ethyl]-anthra[l,9-cd]pyrazol-6(2~)-one and the corresponding amine:
EX~!PLE 4 2-[2-(Diethyla~ino)e'Lh~1]-[[2-(4-morpholinvl?eth amino]anthra[l,9-cd]Pvrazol-6~2~)-one Reaction with ~-(2-aminoethyl)morpholine gives the product as a salt with 2.0 equivaients of hydrogen chloride solvated with 1.2 equivalents of water; mp 288-290C (decomposition).
EX~PLE 5 --- -2-~2-(Diethylamino)ethyl-]-5-[[3-(diethylami-no~oropyl-]- - -amino]antnra[l,9-cd]pyrazol-6(2~)-one Reaction with N,N-diethyl-1,3-propanediamine ~ives the p~oduct as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.2 e~u.ivalent of water; mp 270-272C (decomposition)O
EX~MPLE 6 2-[2-(Diethylamino)ethyll-5-[[7-(dieth~lamino)hep~Yl]
amino]anthra[l,9-cd~pyrazol-6(2H)-one Reaction wi-th N,N-diethyl-1,7-heptanediamine gives the product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.3 equivalent of water; mp 190-192C (decomposition).

5-~[4-(Die~hylamino)butyllamino]-2-[2-(diethylamin ethyl~ thra~l,9-cd]pyrazol~6(2H)-one Reaction with N,N-die.hyl-1,4-butanediamine gives the product as a salt with 2.0 equivalents oE hydro~e~

CLG-l -82-.
c~loride solvated with 0.7 equivalent of water;
m? 2~3-246C (decomposition).

2-[2-(Diethylamino)ethyl!-5-(hex~ltlamino)anthra[l~9-cd]-py~azol-6(2H)-one Reaction with n-hexylamine gives the product as a salt with 1.0 equivalent of hydrogen chloride solvated with 0.1 equivalent of water; mp 176-179C
(decomposition).
2X~PLE 9 2-[2-(Diethylamlno)eth~1]-5-[[2-(1-~iperazin;vl)ethyl]-amino]anthra[l,9-cd]pyrazol-6(2H)-one . . . _ Reaction wi~h 4-(2-aminoethyl)-1-piperazine carboxylic acid, benzyl ester, then hydrolysis of the isolated intermediate with hot 48% hydrobromic acid in acetic acid giv~s the product as a salt with 3.3 equivalents oE hydrogen bromide solvated ~tith 1~4 equivalents of water and 0.1 equiv~lent o -~cetic--- - ---- --~ -acid; mp 284-287C (decomposi-tion). - - -- -4-(2-Aminoethyl)-l-piperazine carboxylic acid, benzyl ester, is prepared from 4-(2-aminoethyl)-1-pipera~ine by a procedure analosous to that described Eor the preparation of (2-aminoethyl)-methylcarbamic acid, benzyl ester, in US Pa~ent 3,931,268; lH NMR
(deuteriochloroform): ~ 2.78 (triplet), 5.08 (singlet), 7.30 ~singlet).

5-[~2-(Diethyl3nino)ethyl]amino]-2-me~hylanthra[l,9-cd~pyrazol-6(2H)-one A mixture o~ 1.88 g (7 mmol) of 5-chloro-2-methylanthra[l,9-cd]pyrazol-6(2H)-one [J. Chem. Soc., 1630 (1952)~, 1.2 g (10 mmol) of N,N-diethylethylene-diamine, 0.14 9 of anhydrous ootassium fluoride, and 10 ml of dimethylsul~oxide is heated at re~lux under argon for four hours, cooled, diluted with water, and e~racted with dichloromethane. The dichloromethane extract is washed twice ~ith brine and then with 53 3~L
CLG-l -83-aqueous hydrochloric acid. The acid solution is washed with dichlorornethane, made basic with sodium carbonate~ and extracted with dichloromethane. The dried dichloromethane layer is clarified with charcoal, filtered, and concentrated to a residue.
The salt was made as described in Example 3 to afford 1.1 g of the dried productS after thorough washing with ether, as a salt with 1.8 equivalents of hydrogen chloride solvated with 0.7 equlvalent of ~ater;
mp 260-264C (decomposition) 5-[~2-[(2-Hydroxyethyl)amino]etnyl]amlno]-2-methy _ anthrall,g-cd]~yrazol-6~2H)-one A mixture of 1.75 g (6.5 mmol) of 5-chloro-2-methylanthra[l,9-cd]pyrazol-6(2H)-one 7 6 ml (59 ~mol) O L 2-(2-aminoethylamino)ethanol, catalytic amounts of anhydrous cuprous chloride and potassium iodlde, and 25 ml of 2-~ethoxyethanol-is-heated:a~-.refl~x under ..~
argon for four.hours, cooled,..and~.concentrated. ~he . ..
residue is dissolved in dichloromethane, washed with water, and then with 5~ aqueous hydrochloric acid.
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 5-15%
methanol in dichloromethane provides the purified product. The salt was made as described in Example 3 to afford 0.69 g of the dried product as a salt ~ith 1.0 equivalent of hy~rogen chloride solvated with 0.1 equivalent of water; mp 270-272C (decomposition).

2-(2-Hydroxyethyl)-5-[[2-[(2-hydroxvethvl)amino]-e-thyl]amino]anthra[l,9-cd]Pyrazol-6(2H?-one A mixture of 896 mg (3 mmol) of 5-ch~oro-2-(2-hydroxyethyl)anthra[l,9-cd]pyrazol-6(2H)-one, 3.1 ml (30 mmol) of 2-(2-aminoethylamino)ethanol, and 6 ml o anhydrous pyridine is heated at reflux under argon for ~2~

8.5 hours, cooled, and concentrated to leave a residue~
Trituration from ether:2-propanol leaves a gummy solid which upon further trituration from rnethanol-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[l,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 60 C 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 of additional product; mp 208-210 C.

5-[[2-(Diethylamino)ethyl]amino]-2-(2-hydroxyethyl)-anthra[l,9-cd]pyrazol-6(2H)-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,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~l,9-cd]-pyrazol-6(2H)-one and the corresponding amine:

CLG-l ~85-EX~PLE 14 2-(2-~ydroxyethyl~-5-[[2-(4-mor2holinyl)ethyl]a-mino]
[l,9-cd~pyrazol-6(2H)-one Reaction with 4-(2-aminoethyl)morpholine gives t~e product as a salt with 1.9 equivalents of hydrogen chloride solvated with 0.5 equivalent of water;
mp 260C (decomposition).

5-[[3-(Diethyla~ino)~ropvl]amino]-2-(2-h~rdroxyethvl)-anthra[l,9-cd3pvrazol-6(2H)-one ~ eaction with N,N-diethyl-1-1,3-propanediamine gives the pro2uct as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.5 equivalent of water; mp 201-210C (decomposition)0 5-[[4-(Diethylamino~butvl~amino3-2-(2-hydroxyeth~
anthra[l,9-cd]Pyrazol-6(2ff)-one Reaction with ~,N-dieth~1-1;4-proparediamin~
- gives the product as a salt with 1.9 equivalent3 o hydrogen chlo~ide solvated with 1.0 equivalent of water; mp 155-185C (decomposition)0 5-~7-~Diethy~amino)hept~rl~a.~ino]-2-~2-llydrcxyethyl)-anthra~l~9-cd~pYrazol-6t2H)-one ~ eaction with N,N-die~hyl-1,7-heptanediamine g ves the product as a salt with 1.0 e~uivalent of hydrcgen chloride; mp 206-208C (decomposition)~

2-12-E~ydroxyethyl)-5-[[2-(1-,~iperazinyl)ethyl~aml -anthra[l,9-cd]pyrazol-6(2~)-one Reaction with 4-(2-aminoethyl)-1-piperazine carboxylic acid, benzyl ester, then hydrolysis of the isolated intermediate with refluxing 48% hydrobromic acid in acetic acid and salt formation gives the prod~ct as a salt with 2.0 e~uivalents OL hydrogen chloride solvated with 0.5 equivalent of water;
mp 292-297C (decompositior.).

CLG-l -86-~, 5-[[2-[(2-Hydroxvethy~amino]ethyl]amino]anthra[l,9_ cd]p~rrazol-6(2H)-one A mixture of 2.54 g ~10 mmol) of 5-chloroanthra-l1,9-cd~pyrazol-6(2H)-one [J_ Chem. Soc., 1630 (1952)], 10 ml (100 mmol) of 2-~2-aminoethylamino)-ethanol, and 25 ml of anhydrous pyridine is heated at re~lux under argon for 24 hours/ cooled, and concentrated. The residue is triturated with 2-propanol ~o 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 1.5 equivalen-ts of hydrogen chloride solvated with 0.6 equivalent of water;
m~ 251-~54~C ~decomposition)~
EX~PLE 20 5-[[2-(Diethylamino)ethyl]amino]anthra~l,9-cd]-pyrazol-6(2H)-one A mixture of 1.6 g (6.3 mmol) of ~-chloroanthra-ll,9-cd]pyrazol-6(2~]-one, 3.5 g (30 m~ol) of N,N-diethylethylenediamine, and 20 ml of anhydrous pyridine is heated at reflux for 20 hours, cooled, and concen~-ated. The residue is dissolved in dichloromethane, washed with water, and then ex~racted with 1% aqueous hydrochloric acid. The acid solution is wasned with dichloromethane, then made basic with aqueous sodium hydroxide. The aqueous solution is e~ract2d with dichloromethane and the dried dichloromethane layer is concentrated to a residue which is converted into a salt as described Eor Example 3 to give 0.7 g of the dried product as a salt with 1.4 equivalents Oc hydrogen chloride solvated with 0.1 equivalent of water; mp 120-130C.

CLG-l -87-2-~2-[(2~H~dro:~yetnyl)amino]ethyl3-5-[[2-~(2-~ydroXy-ethyl~amino]ethyl]amino]anthra[lr9-cd]pyrazol-6(2H) one A mixture of 1.91 g (5 mmol) of 5-chloro-2-[2-~(2-hydroxyethyl)amino]ethyl]anthra[l,9-cd]pyrazol-6(2~)-one, hydrochloride, 2.6 ml of 2-(2-aminoethyl-amino)ethanol, and 5 ml o~ 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 from glacial acetic acid: 2-propanol gives 1.35 g of the dried product as a salt with 1~0 equivalent o~ acetic acid solvated with 0.5 equivalent of water; mp 145-148C.
S-Chloro-2-[2-~(2-hydroxyethyl)amino]ethyl]
anthra[l,9-cd]pyrazol 6~2~)-one is prepared GS
follows:
To a refluxing mix~ure of 832 mg (3 mmol) of 1,4-dichloro-9,10-anthracenedione in 8 ml of dry acetonitrile is added dropwise over 40 minutes, 450 mg (3.8 mmol) of 2-E(hydra~inoethyl)amino]ethanol in 3 ml o acetonitrile. The mi~ture is refluxed for one hour, cooled, and triturated with cold 2-propanol to give 602 mg of product; mp 140-14ZC~ Processing of the mother li~uor affords 71 mg of ad2itional product;
mp 1~4-12-6C. Crystalliza~ion OL the free base from glacial acetic acid gi~es the diacetate salt; mp 125-130C. The hydrochloride salt is prepared ~s described in Example 3; mp 260-263C (decomposition).

CLG-l -8~-2-l~Hydrazinoethyl)amino]ethanol is preQared as ! ~ ollows:
A solution o~ a6 . 3 g (l . O mol) o~ N-(~-h~droxy-ethyl)ethyleneimine and 400 ml (about 6 mol) of 54 aqueous hydrazine is heated at reflux for two days.
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 ~ure material; bp 120C/0.035 mm.

5-~(2-Aminoethyl?amino~-2-[2-1(2-hydroxyethyl~amino]
ethyl]anthra[l,9-cd]pyrazol-6(2H)-one Reaction of 1.91 g of 5-chloro-2-[2-[(2-hydroxy-etnyl)amino]ethyl]anthra[l,g-cd~pyrazol-6(2H)-one hydrochloride with 1.6 ml (25 mmol) of 1,2-ethylene-diamine, as described in Example 21, followed by concentration affords 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 purified over a column of ~P-20 resin eluting first with water and then with methanol. Corlcentration of the methanol eluate followed by sal-t formation as described in Example 3 affords 1.0 5 of the dried product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.9 equivalent of water;
m? 263-267C (decomposition).

CLG-l -89-5-[L2-(Dieth~lamino)ethyl]aminc~]-2-[2-[(2-hydro~y-ethyl amino~eth ~ ,9-cd]~ ol-6(2 )~
one Reaction of 1.91 g of 5-chloro-2-[2-[(2-hydroxy-ethyl)amino]ethyl]anthra[l,9-cd]pyrazol-6(2H)~one, hydrochloride, with 3O5 ml (25 mmol) of N,N-diethyl-ethylenediamine as described in Example 21 affords 1.4 g o product; mp 132-133. Processing of the mother liquor affords 0.3 g of additional product;
mp 130-131C. Salt formation as described for Example ~ gives 1.6 g of the dried product as a salt with 2.0 equi~7alen~s of hydrogen chloride solvated with 1.0 equivalen~ of water; rnp 272-274C (decomposition~.
EX~PLE 24 5-l(2-Hydroxyethyl)amino~-2-[2-[(2-hydroxyethyl) amino]ethyl]anthra~l,9-cd]pyrazol-6(2H)-one A mixture of 2.5 g (6.6 mmol) of 5-chloro-2-[2-I(2-hydroxyethyl)amino~ethyl~anthra[l,9-cd]Pyrazol-6(2H)oner hydrochloride~ 2 ml (33 mmol) of 2-amino-ethanol and 13 ml of anhydrous pyridine is reacted and worXed up as described in Example 21 to afford a solid precipitate whose salt formation as described in Example 3 affords 1.4 g of the d~ied product as a salt with 1.1 equivalents of hydrogen chloride solvated with 0.6 equivalen~ of water; mp 260-261C
(decomposition)~

2-l2-l(2-Hydroxyethyl)amino]e~hyl]-5-[~2 (dim~thyl_ amino)ethyl]amino]anthra[l,9-cd]pyrazol-6(2H)-one ~ eaction 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 CLG-l -90-reflux followed by ~orkup as described in Exa~nple 21 gives a solid residue whose dissclution in not methanol followed by salt formation as described in Example 3 gives 1.0 g of the dried product as a salt with ~.1 equivalen~s of hydrogen chloride solJated with 0.9 equivalent of water; mp 286-288C
(decomposi~ion).

2-[2-[(2-~ydroxyethvl)amino]eth~1]-5 (methylamino)-anthra[l,9-cd]~Yrazol-6(2~)-one -- _ _ Reaction of 5-chloro-2-[2-[(2-hydroxyethyl)-amino]ethyl]anthra[l,9-cd]pyrazol~6-(2H)-one, hydro-chloride, with excess methylamine as described in Example 21 gives the product as a salt with 1 0 equivalent of hydrogen chloride; mp 285-288C
(decomposition).

2-(2-Aminoethyl)-5-[[2-[(2-hydroxyethyl)amino]ethYl]-, amino]anthra[l,9-cd]pyrazol-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 ~nl of anhydrous pyridine is heated at reflux for 30 hours, cooled, and filtered. The filtrate is concentrated and chromatographed over silica gel with 99:2:1 dichloromethane: methanol:triethylamine, then gradient elution ~o 99:20O1 to provide the purified product.
Sal-t forma~ion as describ~d in ExamplP 3 g-ves 0.8 y of the dried product as a salt with 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-~minoethyl)-5-chloroanthra[l,9-cd3pyrazol-6-~2H)-one is prepared as follows:
To a solution of 1.0 g (3.6 T~nole) of l,~-di-chloro-9,10-anthracenedione in 10 ml of pyridine at 35 is added dropwise 1 9 ml of (2-aminoethyl)-hydra2ine [8ritish Patent 880,332]~ Th~ mixture is stirred for four hours, concentrated, and purified on silica gel utilizing 94:5:1 dichloromethane:
methanol:triethylamine. Salt formation as described in ~xample 3 giYes 0~45 g of the product as a salt with 1.0 equivalen~ of hydrogen chloride solvated with 1.2 e~uivalents of water and 0.1 equivalent of 2-propanol; mp 284-285C (decomposition).

2-~2-(Diethylamirlo)ethyll-7,10-dihydroxy-5~[2-[~2 hydroxyethyl)amino]ethyl]amino]anthra[l ! 9-cd]-pyrazol-6(2H)-one __ Reaction of a mixture of 2.9 g (7.5 mmol~ of 5-chloro-2-[2-(diethylamino)e.hyl]-~,10-dihydroxy -----~anthraEl,9-cd~pyrazol-6(2H)-one, 7.5 ml (75 mmol) of 2-(2-aminoethylamino)ethanol, and 35 ml of pyridine for four hours at reflux followed by workup a~
described in ~xample 21 and salt formation as described in Example 3 glves 2~8 g of the dried product as a salt with 2.0 equivalents of nydrogen chloride solvated with 0.7 equivalent of water;
mp 198-202C (decomposition) 5-Chloro-2-[2-~diethylamino)ethyl]-7~10-di-hydroxyanthra~l,9~cd3pyrazol-6~2H)~one i5 prepared as follows:
Reaction of a mix~ure of 12.7 g (41 mmol) of 1,4-dichloro-5,8-dihydroxy-9,10~anthracenedione, 12 g (90 mmol) o (2-diethylaminoethyl)hydrazine, and 65 ml o pyridine at 50C for four hours follo~ed by workup s~,~
CLG-l -92-as described in Example 22 ~ives a residue that is dissolved in dichloromethane Chromatography over silica gel with dichloromethane and then with ~%
methanol in dichloromethane affords crude material whose crystallization from 2-propanol gives ~.5 g of a purified solid; mp 136-140C. Salt formation as described in Example 3 on lo 5 g of ~his material gives 1.3 g of a dried solid as a salt with 1.0 equivalent o~ hydrogen chloride solvated with 0.3 equivalent of water; mp 280-282C (decomposition)~
EX~MPLE 29 2-~2-(Diethylamino)ethyl]-5-[~2-(diethylamino)ethyl]-amino]-7,10-dihydrox~an~hra[1,9-cd]pyrazol-6(2H~-o Reaction of a mixture o~ 1093 g (5 mmol) of 5-chloro-2-[2-(diethylamino)ethyl]-7~lo-dihydroxyanthra Il,9-cd]pyrazol-6(2~)-one, 2.g g (24 mmol) of N,N-diethylethylenediamine, and 25 ml of pyridine-for fi-ve - '~ --'- ~
hours at reflux ~ollowed-by workup ~s-described in Example 21 gives a crude solid which is dissolved in dichlorome~hane. Chromatography over silica gel with 3~, 6~, and 10% solutions of methanol in dichloromethan~ affords 1.6 g o~ pure material. Salt ormation as described in Example 3 gives 1 4 g of the dried product as a salt with 2.0 equivalents of hydrogen ~hloride solvated with 0.3 equivalent of water; mp 290-292C (decomposition) EX~MPLE 3 5-~(2-Aminoet'nyl)amlno]-2-[2-('di'ethylamino)_th 7,10-dihydroxyanthra~l~9-cd]p~raz-ol--6(2H~-one ~ eaction of 5-chloro-2-~2-(diethylamino~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 chlorid* solvated with 1.7 equivalents oE water and 0~1 equivalent of 2-propanol; mp 277 281C
~decomposition).

CLG-l -93-EX~MPLE 31 2-[2-(Diethylamino)ethvl]-7,10-dihydr x~-5-[[2~
-(met_yla~ino)ethyl]amino~ant~hra[lt9-cd]pyra 6(2H)-one Reaction of 5-chloro-2-[2-(diethylamino)ethyl]-7,10~dihydroxyanthra[1,9-cd]pyrazol--6(2H)-one with ~2-aminoethyl)-methylcarbamic acid, benzyl ester [US Patent 3,931,268] followed by isolation of the intermediate as described in Example 29 then hydrolysis with hot 48~ hydrobromic acid in acetic aciA gives the product as a salt with 2.3 equivalents of hydrogen bromide solvated ~ith 2.7 equivalents o, water; mp 217-220C (decomposition).

2-~2-(Dimethylamino)ethyl]-7,10-dihydroxy-5-~[2-~[(2-hvdroxy~hy_~mino]ethyl]amino]anthra[1,9-cd_pyrazol-6(2~)-one Reaction of 2.0 g (5.6 mmol) o~ 5-chloro-2-[2-tdimethylamino)ethyl]-7,lo-dihydroxyanthra-l~9-cd]- -pyrazol-6(2H3-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 formation as described in Example 3 yives 2.4 ~ of the dried product as a salt with 2~4 equivalents of hydrogen chloride solvated wi~h 2.0 eauivalents of water, mp 310-313C (decomposition).
5-Chloro-2-[2-(dimethylamino)ethyl]-7,10-dihydroxyanthra[l~9-cdlpyrazol-6(2~)-one is ~repared as follows:
Reaction of a mixture of 15.5 g (50 mmol) of 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione, 10.3 g (100 mmol) of (2-dimethylaminoethyl)-hydrazine ~J. Med. Chem., 1;493 (1964)] and 60 ml _. _ of pyridine at 35C overnight followed by ~orkup as described in ~xample 28 gives 3.8 g of product;
mp 143-146C. Salt formation as described in CLG-l -94~
Example 3 g7 ves ~he product as a salt with 1.1 equivalents of hydrogen chloride solvated with 1.2 equivalents of water; mp 295-300C
(decomposition).
The following compounds are prepared as described in Example 32 from 5-chloro-2-[2~(dimethylamino)~
ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one and the corresponding amine:
EX~MPLE 33 5-~(2-Ami~e~ in~l-2~ (dimethylamino)ethyl]-7,10-dihydroxyanthra[l~9-cd] pyr2ZOl- 6 (2H)-one Reaction with ethylenediamine gives the product a3 a salt with 1.9 equivalents of hydrogen chloride solvated wi~h 2.4 equivalents oE water; mp 300-302C
~decomposition).
EXAMPL~ 34 5-[t3-Aminopropvl)amino]-2-[2-(dimethylamino)ethx~]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2~)-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 281-285C (decomposition).

5-~[2-(Diethylamino)ethyl]amino]-?~lo-dihydroxy 2-(2-hydroxyethyl)anthra[l,9-cd]pyrazol-6(2H) one Reaction of a mixture of 3.3 g (10 mmol) of S-chloro-7 t 10-dihydroxy-2-(2~hydroxyethyl)anthra~
¦1,9-cd]p~razol-6(2H)-one, 14;5 ml (100 mmol~ of N,N
diethylethylenediamine, and 20 ml of pyridine Eor ~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 of the dried product as a salt with 1~6 equivalents of hydrogen chloride solvated with 0.6 equlvalen~ of water; mp 215-219C (decomposition).

f ~:~S1~3~
CLG-l -95-5-Chloro-7,10-dihydroxy-2-(2-hydro~yethyl)anthra-`~ {l,9-cd]pyrazol-6(2H)-one is prepared as follows:
~ mix~ure of 12 g (40 ~nol) of 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione7 4~5 g (60 mmol) of (2-hydroxyethyl)hydrazine, and 40 ml of pyridine is stirred at 50C overnight, cooled, and concentrated.
The residue is triturated successively with chlorofor~
and hot ~ethanol to give 1.1 g of the dried product;
mp 231-234C.

5-[[2-[(2-Hydroxyethyl)amino]ethyl]amino]-7,10-dihydroxy-2-(2-hy~roxyethvl)anthra[l~9-cd]pyra 6(2H)-one A mixture of 303 g (10 mmol~ of 5-chloro-7~10-dinydro~ 2 (2-hydroxye~hyl)an~hra[1~9-cd~pyrazol-6(2H)-one~ 1004 g (100 ~mol) of 2-(2-aminoethylamino)-ethanol, and 20 ml of pyridine i5 heated at rerlux for four hours, cooled, and concentrated. Successive tritura~ion of the residue with acetonitrile, ~-propanol, and methanol gives 1.35 g of a powder.
Salt ~ormation as described in Example 12 affords 1.06 y oE the dried product as a salt with 1.0 equivalent ~f hydrogen chloride sclvated wi~h 0.5 equivalen~ of water; mp 196-203C (decomposition) The following co~pounds are prepared as described in Example 35 from 5-chloro-7,10-dihydrox~y-2 (2-hydroxyethyl)anthra~l,9-cd]p~razol-6( 2HA ) -one and the corresponding amine:
EX~MPLE 37 5-[(2-Aminoeth~,~l)aJnino]-7,10~dihydroxy-2-(2-hs~droxy ethvl)anthra[l,9-cd]pyrazol-6(2H)-one Reaction with ethylenedia.~ ne gives the product as a salt with 1.8 equ valents of hydrogen chloride solvated with 0.5 equivalent of water; mp ~195~C
tdecomposition).

CLG-l -96-EX~PLE 38 7,10-Dihydrox~-2-t2-hydroxyethyl)-5-[[2-(4-mor~holinyl)ethvl]amino] anthra [1,9-cd]
p~razol-6(2~)-one Reaction wi-th 4-(2-aminoethyl)morpholine gives the product as a salt with 0.4 equivalent o hydrogen chloride and 0.3 equivalent of water; mp 240-251C
(decomposition)~

5-[l2-(Dimethylamino)ethyl3amino]-7,10-dihydroxy-2-(2-hydroxyethyl)anthra[l~9-cd~pyrazol-6~26) one Reaction with N,N-dimethylethylenediamine gives the produc~ as a salt ~ith 1.5 equivalents of hydrogen chlo-ride solva~ed with 2.0 e~ui~7alents o water, mp 250C ~decomposition~
EX~MPLE 40 5-[(2-~minoethyl)amino]-7,10-dihydro~r-2-methvl-- -~
anthra[l,9-cd]Pvrazo1-6(2~)-one Reaction of a mixture of 3 2 g (10.6 mmol) of S-chloro-7 r 10-dihydroxy-2-methylanthra~l,9-cd]pyrazol-6(2H)-one, 5 ml (7~ mmol) of ethylenediamine, and 55 ~1 of pyridine for sevell hours at r~flux fol].owed by workup as described in Example 21 gives a solid residue. Dissolution of the solid in hot methanol and N,N-di~ethylformamide followed by salt formation as described in Example 3 affords 1.5 g of ~he dried prodl~ct as a salt ~lth l~0 equivalent of hydrogen chloride solvated with 0.2 equivalent of water and 0.1 equivalent of N,N~dimethylEormamide; mp 323-326C
[decomposition).
5-Chloro-7~10-dihydroxy-2-methylanthra[l,~-cd]-pyrazol-6t2~)-one is prepared as follows:
A mixture of 12.4 g (40 mmol) of 1,4-dichloro-5,8-dihyd~oxy-9,10-anthracenedione~ 2.7 ml (50 mmol~
of methylhydrazine, and 250 ml of pyridine is heated at 35C for seven hours, treated with an additional ~,2~ 3~

~LG-l -97-1 ml of methylhydrazine, heated for seven hours at 35C, and cooled. The solids are filte~ad and recrystallized from N,N-dimethylformamide to give 8.85 g of the dried product as a salt with 0.1 equivalent of hydrogen chloride, mp 298-305C
(decomposition).

7,10-~ihydroxy-5-[[2-[(2-hydroxyethvl)amino]ethvl~-amino]-2-methylanthra[1,9-cd]py-azol-6(2H)-one Reaction of a mixture of 3.25 g (10.8 mmol) of 5-chloro-7,10-dihydroxy-2-methylanthra[l,9-cd]pyrazol-6(2H)-one r 3 ~1 (30 mmol) of 2-(2-aminoethylamino)-ethanol, and 50 ml of pyridine for seven hours at reflux fo'lowed by wor~up as described in Example 21 and salt formation as described in Example 3 gives 1.8 g of the dried product as a salt ~ith 1,0 equivalent of hydrogen chloride solvated with 0.6 equivalen.t of ~ater;-~.p-280-284C-(decomposition)~
EX~MPLE 42 5-[[2-(Diethylamino)ethyl]amino]-7,10-dihydroxy-2-methylanthra[l,9-cd]pyrazol~6(2H)-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)-one, 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 described in Example 3~gives 1.7 g o ~he dried product as a salt with 1.5 equivalents of hydrogen chlor~de solvated with 0.8 equivalent of water; mp 298C (decomposition).

2-[3-(Diethylamino)-2-hydroxypropyl]-7,10-dihydroxy-5-[[2-[(2-hydroxvethyl)amino]et-~yl]amino]anthra tl,9-cd]pyrazol-6(2H)-one Reaction of a mixture of 1.3 g (3 mmol) of S-chloro-2-[3-(diethylamino)-2-hydroxypropyl]-7,10-dihydroxyanthra~l,9-cd]pyra~ol-6(2H)-one, 2.1 ml .

3~
CLG-l -98-(21 mmol) of 2-(2-aminoethylamino)e~hanol, and 10 ml o pyridine at reflux for six hours follo~ed by wor3cup as described for Example 21 and salt forrnation as described in Example 3 gives the prod~ct 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-2-13-(diethylamino)-2-hydroxypropyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-5(2~)-one is prepared as follows:
A mixture of 6.2 g (20 mmol) of 1,4-dichloro~
S,8-dihydroxy-9,10-anthracenedione, 9~7 g (60 Ir~,ol) of l-(diethylamino)-3-hydrazino-2-propanol (German Patent 1,126,877) and 3S ml of pyridine is stirred at 40C
for one nour then at room temperature overnight The mixture is concentrated and purified on silica gel utilizing 97:2:1 dichloromethane methanol:
triethylamine to give 1.7 g of product. Salt formation as described in Example 3 gives 1.4 g of the product as a sall with 1.0 equivalent of hydrogen chloride solvated with 0.7 equivalent of wa.er; mp 264-267C (decomposition).

5-~[2-(Diethylamino ? ethyl]amino]-2-[3-(diethYlamino)-2-hydroxypropyl]-7,10-dlhydroxyanthra[1,9-cd]pyrazol-6(2H)-one Reaction o 5-~hloro-2~13-~diethylamino)-2-hydroxypropyl]-7,10-dihydroxyanthra~l,9-cd]pyrazol-6(2H)-one with N,N-diethylethylenediamine as de~cribed in Example 43 gives the product as a salt with 2.0 equivalents of hydrogen chloride solvated with 1.9 equivalents of water; mp 253-255C (decomposition).
EXA,~qPLE 45 5-~(2-Aminoethyl)amino]-2-[3-(diethylamino)-2~hYdroxy-propyl]-7,10-dihvdro~yanthra[l,9-cd]pyrazol-6(2~1)-one Reaction of 5-chloro-2-[3-(diethylamino)-2-hydroxypropyl]-7,10-dihydroxyanthra[1,9-cd]pyrazol-~ z~ 3~

CLG-l -99~
6(2H)-one wi~h ethylenediamine as described in Example 43 gives the product as a salt r~ith 2.0 equivalents of hydrogen chloride solvated with 2.8 equivalents of water; mp 148-152~.

2-[3-(Dimethylamino)pro~yl]-7rlu-dihydroxt~-5-[[2 [(2-hydroxyethyl)amino]eth~]amino]anthra~l,9-cd]
pyrazol-6(2H) one ~ eaction of a mixtura of 2.5 g (6 mmol) of 5-chloro-2-l3 (dime~hyLamino)propyl]-7,10-dihydroxy-anthratl,9-cd]pyrazol-6(2H)-one~ hydrochloride, 2.8 ml (28 mmol) of 2-(2-aminoethylamino)e~hanol, and 20 ml of pyridine a~ reflux for 24 hours follo~ed by workup as described for Example 21 and salt formation as described in Example 3 gives the produc~ as a salt with ~.0 equivalents of hydrogen chloride solvated with 1.0 e~uivalent o water; mp 311C
(decomposition).
5-Chloro-2-~3-(dimethyla~ino)prop~1]-7,10-dihydroxyanthra[l,9-cd~pyrazol-6(2H)-one is prepared as follows:
To a suspension of 30.9 g (100 mmol~ o~ 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 lJ. Med. Chem., 1;493 (1964)]. The mixture is dilu-ted with 50 ml of N,N-dimethyl~ormam;de, stirred for ten hours7 and concentrated. The residue is dis~ribu~ed betT~een dichloroT~ethane and 5% aqueous sodium bicarbonate.
Puriication of the dried organic layer on silica gel - utilizing 95.5:4:0.5 dichloromethane:methanol:
triethylamine gives 8 9 of product. Salt formation as described in Example 3 gives 7.6 g of the 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-Amino~ropyl)amino]-2-[3-(dimethylamino)propyl]-7,10-dlhydrox~anthra[1,9-cd]pyrazol~6(2H~-one Reaction of 5-chloro~2-[3-(dimethylamino)propyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H)-one, hydro-chloride, with 1,3 propanediamine as desc-cibed in Example 46 gives the product as a salt with ~.0 equi~alents of hydrogen chloride solvated with 0.5 equivalent of water; mp ~300Co 7,10-Dihydroxy-5-[[2~[(2-hydroxyethyl)am~no]ethyl~-amino-2-~2-~methylthio) ethyl ) anthra~l,9-cd]-pyrazol-6(2H)-one Reaction of a mixture of 0.66 g (3.6 mol) of 5-chloro-2~~2 t-hiome~hylethyJ)-7~lo-dihydroxyanthra~
Il,9-cd]pyra~ol-6(2H) one, 1.8 ml ~18 mmoli of 2-~2-aminoethylamino)ethanol, and 16 ml of pyridine at reflux overnight followed by workup as described in Example 21 and salt formation 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
(decompqsition).
5-Chloro-2-t2-thiomethylethyl)-7,10-dihydroxy-anthra-~,9-cd]pyrazol-6(2H)-one is prepared as follows:
An ice-cold mixture of 2.64 g (5 mmol) of 5-chloro-2-(2 thiomethyleth~L)-7,10-bis(phen~
methox~) anthra[l,9-cd]pyrazol~6~2H)-one in 15 ml dichloromethane is treated dropwise during 30 minutes wi~h 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 mixture is warmed to room temperature overnigh~ then concentrated to a residue which is triturated with 2-propanol to give a red solid. Fur~her trituration !

C~G-l -101-with 75 ml of boiliny methanol gives 0.9 g of pure product; mp 186-190C.
5-Chloro-2-(2-thiomethylethyl)-7,10-bis(pnenyl-methoxy)anthra[l,9-cd]pyrazol-6(2~)-one is prepared ~s ollows:
A mixture of 5.1 g (10 mmol) of 5-chloro-2-(2-hydroxyethyl)-7,10-bis(phenylmethoxy)anthra-~1,9-cd3pyrazol-6(2H)-one, 9.4 g (100 mmol) of methyl-disulfide, 20.2 g (100 mmol) of tri-n-butylphosphine, and S0 ml of N,N-dimethylformamide is stirred over-night at room temperature. The mixture is cooled and treated carefully with 75 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 155-160Co S-Chloro-2-(2-hydroxye~hyl)-1,10-bis(phenyl-methoxy)anthra[l,9-cdjpyrazol-6(2H)-one is prepared as follows:
Reaction of a mixture of 35.~ g (72 mmol) of 1,4-dichloro-5,8-bis(phenylmethoxy)-9,10-anthracenedione,

11.2 g (147 mmol) of (2-hydroxyethyl)hydrazine, 2.1 g (37 ~mol) of anhydrous potassium fluoride, 7.4 g (74 mmol) of 2nhydrous potassium bic~rbonate, and 220 ml o~ dry dimethylsulfoxide as described in Example S4 gives 33.1 g of the dried product;
mp 118-184C. Crystallization from chloroform raises the melting point to 201-~04Co 1,4-Dichloro-5,8-bis(phenylme~hox-y)-9,10-anthra-cenedione is prepared as follows.
A mixture of 51.3 g (160 mmol) of 1,4-dichloro-~8-dihydroxy-9,10-anthracenedione (US Paten~ Number 3,631,0~4), 46 g (330 mmol) OL powdered anhydrous potassium carbona~e, 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 washed se~uentially with water, !

~25~3~
CLG-l -102 methanol, and diethyl ether to give 63.~ g of the dried product; mp 190-194C. Processing of the acetone filtrate gives 9.4 g of a second crop' mp 142-155C.

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 mmol) of S-chloro-2-~2-(diethylamino~ethyl]-7,10-bis(phenyl-methoxy)anthra~l,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~
Follo-~ing addition, the mixture is treated carefully with 30 ml of methanol. The mixture is warmed to room temperature overnight and the solid residue is collected, washed sequentially with 2-propanol, methanol, and diethyl ether to give 5.5 g of the dried product as a salt with 1~0 -equivalent of nydrogen ~-chloride, and solvated with 0.2 equivalent of water;
mp 280-282C (decomposition~.
5-Chloro-2-[2-(diethylamino)ethyl]-7,10-bis-(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follo~s:
A mixture of 4.2 g (6.3 mmol) of 5-chloro-2-~2-~1(4-methylphenyl)sulfonyl]oxy]ethyl~-7,10-~is(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one, 4.~ g (60 mmol) of diethylamine, 17 g (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 ~ o product mp 209-211C.
S-Chloro-2-[2-[[(4-methylphenyl)sulfonyl]oxy]-ethyl]-7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2~)one is prepared as follows:

~25~
CLG-l -103-An ice-cold mixture of 22 g (43 mmol) of 5-chloro-2~(2-hydroxyethyl)-7,10-bis~phenyl-methoxy)anthrall,9-cd]pyrazol-6(2H)-one, 12.3 y (65 mmol~ o ~-toluenesulfonyl chloride and 170 ml of pyridine is stirred for .~0 hours. The solid is Eiltered, washed with methanol and diethyl ether, and dried to give 10.5 g of the product; m~ 203-206C
~decomposition). Processing of the filtrate gives 9.3 g of additional product; mp 182-188~C
(decomposition).

2-[2-l~2-(Dimethylamino)ethyl]amino]ethyl]-5-[l2-[(2-hydrox~ethyl~amino]ethyl]amino]-7,10-dihvdroxyanthra-fl,9-cd~pyrazol-6(2H)~one ~ eaction of a mixture o~ 3 6 y (7 4 mmol~ 5~
chloro-2-[2-~[2-(dimethylamino)eth~yl]arnino]ethyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6~2H)-one, dihydrochloride, 4.5 ml ~45 ~mol) of 2-(2-aminoethyl- f --amino)ethanol, and 35 ml of pyridine at 80C overnight followed 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~te~; ~p 110-117Co 5-Chloro-2-[2-[~2-(dimethylamino~ethyl]amino~-ethyl] ~7 ~10-dihydroxyanthra~l,g-cd]pyrazol-6(2H)-one is prepared as followsO
An ice-cold mixture o 9.-3 g tl6 mmol) of 5-chl~ro-~-[2~l2-(dime~hylami~no)e~hyllamino]e~hyl~-7tl0-bis-~Phenylmerhoxy)an' h~a[l,9~cdJpyrazol-~(2H)-one in 30 ml of dichloromethane is treated dro~wise during t~70 hours ~ith 96 ml of a 1 M solutlon of boron trichloride~ Following addition, the mixture is treated carefully with 30 ml of methanol The mixture is warmed to room tempera.ure overnight and the solid resiaue is collected, washed sequentially with 2-propanol, methanol, and diethyl ether to give 3.68 g of the dried product as a salt with 1.8 ~2~
CLG-l -104-equivalents of hydrogen chloride and solvated "ith 0.2 equivalent of 2-propanol and 0.8 equivalent of water;
mp ~60-268C (decomposition).
~Chloro-2--[2-[~2-(dimethylamino)ethyl]amino]~
e'cshyl]-7,10-~is(phenylmethoxy)anthra[l,9-cdlpyrazol-6(2H)-one is prepared as follows:
A mixture of 4.2 g (6.3 mmol) of 5-chloro-2-[2-t[(4-methylphenyl)sulfonyl~oxy]ethyl'J-7,10-bis~phenyl-methoxy)anthra[l,9-cd]pyraol-6(2H)-one, 5~3 9 (60 mmol~ of N,N-dimethylethylenediamine, 17 g (12.6 mmol~ of powdered potassium carbonate, and 35 ml of dimethylsulfoxide is stirred overnight at 50C.
The mixture is cooled and diluted with 50 ml of water.
The solid is collected and washed with water~ The solid is heated in dichloromethane~ the solution iltered, then concentrated Trituration of the residue with hot ethyl acetate gives 1.7 g of the dried product; mp 148-153C~ . - -7,10-Dihydroxy 5-[~2-[(2-hydrox~ethyl)amino~ethyl]-amino]-2-[2-[(2-hydroxyethyl~methylamino]ethyl]-anthra[l~9-cd]p~azol-6(2H)-one Reac~ion of a mixture of 3.3 g (1.3 mmol) of 5-chloro-7~10-dihydroxy-2 ~2~[(2-hydroxyethyl)-methylamino]ethyl~anthra[l,9-cd]pyrazol-6(2H)-one, hydrochloride, 3.6 ml (36 mmol) of 2-(2-aminoethyl-amino)ethanol, and 30 ml of pyridine oYernight at 80C
followea by wor'~up as described :in Fxample 21 and sal~
forma~ion as described in Example 3 gives 1..~ g of the dried product as a salt wiLh 1~6 equivalents of h~drogen chloride solvated w~th 0.4 equivalent of water; mp 240C (decomposition).
5-Chloro-7,10-dihydroxy-2-[2-[(2-hydroxyethyl)-methylamino]ethyl]anthra[l,9-cd]pyrazol-6(2H)-one i5 prepared as follows:

, ~5~3 ~LG-l -105-Reaction of a mixture of 8.3 g (15 mmol) of 5-chloro-2~[~-[(2-hydroxyethyl)methylamino~ethyl]-7,10-bis(phenylme~hoxy)an~hra[l,9-cd3pyrazol-6(2~)-one, 87 ml o a 1 M solution o boron trichloride in dichloromethane, and 60 ml of dichloromethane as described for Fxample 49 gives 3.5 g o the dried product as a salt with 1.0 equivalent of hydrogen chloride solvated with 1.75 equivalents o water;
mp 279-282C (decomposition~, 5-Chloro-2-[2-[(2-hydroxyethyl)methylamino]
ethyl]-7,10-bis(pherlylme~hoxy)anthrall,9-cd]pyrazol-~(2H)-one is prepared as ollows:
Reaction o a mixture of lOo0 9 (15 mmol) of 5-chloro-2-[2-[[4-methylphenyl)sulfonyl]oxy]ethyll-7,10-bis(phenyl)methoxy)anthra[l,9-cd]pyrazol-6(2H)-one, 12.1 ml (150 mmol) of 2-m~thylaminoethanol, 4.1 9 (30 mmol) of potassium carbonate, and 90 ml of dimethylsuifoxide-as described in Example -49 gives -- -8.5 g of the product; mp 191-194C.

7,10-Dihydroxy-5-[[2-[(2-hydroxyethyl)amino]etnyl~-amino ! -2-[3-[(2-hydroxyethvl)amino]propyl]anthra-[l,g-cd]pyra~ol-6(2H)-one Reaction of a mixture of 1.4 g (3.6 mmol~ of 5-chloro-7,10-dihydroxy-2-[3-[(2-hydroxyethyl)a~ino]-propyl]anthra[l,9-cd]pyrazol-6(2H)-one, hydrochloride, 3.7 ml (37 mmol) of 2-(2-aminoethylamino)e!ha~ol and 15 ml oE ~yridine overnigh~ at 80C follow?d by worXup as described in Example 21 gives 0.9 g of ~he dried produc~. solvated with 0.6 equivalent of water; mp 10~-105C.
5-Cbloro-7,10-dihydroxy-2-[3-[(2-hydroxyethyl)-amino]propyl]anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follo-~s:

;6D~
CLG-l -106-Reaction of a mixture o 9.0 g (16 mmol) of ! 5-chloro-2-[3-~(2-hydroxyethyl)amino]propyl]-7,10-bis(phenylme~hoxy)anthra~l,9-cd]pyrazol-6(2H)-one, 63 ml of a 1 M solution of boron trichloride in dicAloromethane, and 30 ml of dichloromethane as described for Example 49 gives 6.0 g of the dried product as a salt with 0.8 aquivalent of hydrogen chloride solvated with 0.7 equivalent of water;
mp 255-265C (decomposition).
5-Chloro-2-[3-l(2-hydroxyethyl)amino]propyl]7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one is prepar2d as follows:
Reaction of a mixture of 13 4 g (19.7 TT~ol) of 5-chloro-2-~3-[[4-methylphenyl)sulfonyl]oxylpropyl]-7,10-bis(phenylmethoxy)anthra~l,9-cd]pyrazol~6(2H)-one, 12 ml (197 n~ol) of 2-aminoethanol, 5.5 g (39.4 mmol) of potassium carbonate, and 120 ml of dimethylsulfoxide as de.scribed in.~xample 49~gives~
~.85 ~ of the product, mp 174-176C. Crystallization Erom chloroorm gives material o mp 180-18SCo 5-Chloro-2-[3-[[4-me~hylphenyl)sulonyl]oxy~
prop~ 7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
Reaction of a mixture of 130 1 9 (25 TT~01) of 5-chloro-2-(3-hydroxypropyl)-7,10-bis(phenylmethoxy)-anthra[l,9-cd]pyrazol-6~2H)-one~ 9~5 g (S0 TT~ol~ of ~-toluenesul~onyl chloride, 9 ml (65 mmol) of triethylamine r lS0 mg of 4-dimethylaminopyridine, and 125 ml of dichlorome~ha?la at 5C for one day ~hen at room temperature for ive hours followed by wor'~up as described for Example 49 gives 14.3 g of the product;
mp 137-139C.
-S-Chloro-2-(3 hydroxypropyl)-7,10-bis(phenyl-methoxy)anthra~l,9-cd]pyrazol-6(2H)-one is prepared as ollows:

~,2~
CLG-l -107-A mixture of 48.9 g (100 mmol) of 1,4-dichloro-5,8-bis(phenylmethoxy)-9,10~-an~hracenedione, 18 0 g (200 mmol) of ~3-hydroxypropyl)hydrazine [J. ~ner.
Chem. Soc. _ , 1283 (1954)1, 2.9 g (50 mmol) af anhydrous potassium fluoride, 10.0 g (100 mmol) of anhydrous potassium bicarbonate, and 300 ml of dry dimethylsulfoxide is stirred at 80C overnight. The warm mixture is diluted with 1.5 ml of water, then allowed to cOOla The solids are collected by filtra-tion, washed sequentially wi~h water, 2-propanol, and diethyl ether to afford 31.0 g of the dried product;
mp 159-163C. Processing of the filtrate gives 4.7 9 of additional product, mp 150-154C~
EXAMPL~ 53 5-~(3-Aminoeropvl)amino]-7,10-dih~droxy-2-[3~[(2-hydroxyethyl)amino]propyl]anthra[l,9-cd]pyrazol-6(2H)-one Reaction of a mixture of 1.3 g (3.3 mmol) of 5-chloro-7,10-dihydroxy-2-l3-[(2-hydroxyethyl)amino~-propyl]anthra[l,9-cd]pyrazol-6(2H)-one, 2.9 ml (35 mmol) of 1,3-propanediamine~ and 15 ml of pyridine at 80C overnight followed by workup as described in Example 21 gives 1.0 g of the dried product as a salt ~-th 0.1 equivalent of hydrogen chloride solvated ~ith 0.3 equivalent of water and 0.1 equivalent oE
2 propanol; mp 120-130C (decomposition).
E~AMPLE 54 7,10-Dih~droxy-2-[2-[(2-hydrox~ethYl~amino~thyl]~5 t [ 2- [(2-hydroxyeth~l?amino]ethyl]amino]a_hra[l,9-cd]-pyrazol-6(2H)-one Reaction of mlxture of 1.28 g (3 mmol) 5-chloro-~,10-dihydroxy-2[2-[(2-hydroxyethyl)amino]ethyl]-an~hra[l,9-cd]pyrazol-6(2H)-one; hydrochloride, 1.5 ml (15 mmol) of 2-(2-aminoethylamino)ethanol and 6 ml of pyridine at 80C overnight followed by workup as described in ~xample 21 and salt formation as described in ~xample 3 giVQs 675 mg of the product as ~2~
CLG-l -108~
a salt with 2~0 equivalents of hydrogen chloride ! solqated ~ith 0.9 equivalent of water; mp 215-225~C
(decomposition).
5-Chloro-7,10-dihydroxy-2-[2-[(2-hydroxyeth~l) amino]ethyl]anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
To an ice-cold mixture of 2608 g (48 mmol) of 5-chloro-2-[2-[hydroxyethyl)amino]ethyl]-7,10-bis-(phenylmethoxy)an~hra[l,9-cd]pyrazol-6(2H)-one and 60 ml of dry dichlorornethane is added dropwise during 2 1/~ hours 794 ml o' a 1 M solution of boron trichloride The mixture is stirred for an additional 0.5 hours~ then 200 ml OL methanol is a2ded dropwis~
during lo 5 hoursO The mixture is allowed to ~7arm to room temperature overnigllt and the solids are fil-tered, washed sequentially with methanol~
dichloromethane, diethyl ether, and 2-propanol to give 14~7 g of the dried product; mp 175C (decomposition)-.~ ~~
Processing of the filtrate affords 5.4 g of additional product; mp lZ5-135C (decomposition)O
Crystallization of the solid from m~thanol gives a salt with 1.~ equivalent of hydrogen chloride solvated with 0.7 equivalent of water; mp 180-200C
(decompcsition~.
5-Chloro-2-~2-[(2-hydroxyethyl)amino]ethyll-7~10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2~)-one is prepared as ~ollows~
.~ mi~ture o~ 58/8 g (120 ~mol) ~f 1,4~dichloro--~,8-bis(phenylmethoxy)-9,10~anthracenedione~ 28.6 y ~240 mmol) of 2-[(hydrazinoethyl)amino]ethanol~ 3.S g ~60 mmol) of anhydrous potassium fluoride, 12 9 (120 mmol) of anhydrous potassium bicarbonate, and 360 ml of dry dimethylsu]oxide is stirred at 80C overnight.
The mixture is diluted with 400 ml of water and the orange solids are filtered, washed sequentially with water, 2-propanol, and diethyl ether to give 51.2 g of the dried product; mp 164-1O8C

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

5-[(2-~minoethyl)amino]-7,10-dihydroxv-2-~2-[(2-hydroxyethyl)amino]e~ l]anthra[l,9-cdlpyrazol-6(2H)-one Reaction with ethylenediamine gives the product as a salt with 2.0 equivalents o~ hydrogen chloride sol~7ated with 0.9 equivalent of water; mp 272-278C
(decomposition~
~ X~MPL~ 56 5-[[2-(Di~ethyla~ino)ethYl]amino]-7,10-dihydroxy-2-[2-[(2-hydrox~ethyl ? amino]ethYl]anthra[1,9-cd3-pyra~ol-6(2H)-one Reaction with N,N-dimethylethylenediamine gives the product as a salt with l.9 equivalents of hydrogen chloride solvated with 1.7 equi~alents OL water;
mp 278-280C (decomposition).

5-[[2-(Diethylamino?e~hyl]amino]-7,10-dihydroxy-2-[2-[(2-hydroxyethvl)amino]ethyl]anthra[l,9-cd]pvrazol-~(2H~-one Reaction with N,N-die~hylethy~enediamine gives the product as a salt with l.9 equivalents of hyd~ogen chloride solvated with 1.5 equivalents of water;
mp 228-231~C.

5~[(3-Aminopropyl~amino]-7,10-dihydroxy-2-[2-t(2-hydroxyethyl)amino~ethyl]an~hra[l,9-cd]pyrazol-6-~2 ~-one Reaction with l,3-propanediamine gives the product as a salt with 1.7 equivalents of hydrogen chloride solvat2d with l.0 ~quivalent o~ water;
mp 222C (decomposition).

~,~s~
CLG-l -110-EX~ PLE 59 5-~(4-Aminobut~l)amino]-7,10-dihydroxy-2-[2-[(2-hydro~
ethyl)amino]e~h, ~ ~nthra[l,g-cd]Dyra~ol~5(2H)-Gne Reaction with 1,4-butanedia~ine gives the product as a salt with l.0 equivalent of hydrogen chloride solvated wi~h 0.5 equivalent of water; mp 240-245C
(decomposition)~

5-~(5-Amir.opentyl)amino]-7,10-dihydroxv-2-[2-~(2-hydroxvethyl?amino]ethyl]anthra[l,9-cd]2yra 6t2H)-one Reaction with 1,5-pentanediamine gives the product as a salt with l.9 equivalents of nydrogen chloride solvated with 0.7 equivalent of water;
mp 270-275C (decomposition), 7,10-Dihydroxy-2-[2-[(2-hxdroxvethyl)amino]ethyl]
5-[[2-t4-morphoiln~l)ethyl3aminc]ant,~nr~[1,9-cdl~
pyrazol-6(2H)-one Reaction with 4-(2-aminoethyl)morpholine sives the product as a salt with 2.4 equivalen~s of hy~rogen chloride solvated with 0.8 equivalent of water;
m~ 280C (decomposi~ion)~
EXAMPL~ 62 ?, lO-Dihydroxy-2-[2-[(2-hydroxyethyl)amino]ethyll-5 [[3-1(2-h~rdroxyethyl)amino]propyl]aminolanthra[l~9-cd3 pyra~ol-6(2H)-one Reaction with 2-(3-a~inooropyla~ino)ethAanol gives the product as a salt with 2.1 e~uiJalents of hydrogen chloride solvated with 0.8 equivalent o~ water and 0.1 e~uivalent of 2-propanol; mp 170-180C
(decomposition).

~5~q~3~
CLG~
E~AMPLE 63 5-1l2-[[2-(DimethYlaminoethyl_amin _~th~amlno]-7 ! 10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]anthra-[l,9-cd]pyrazol-6(2H)-one Reaction with N,~l-dime~hyldiethylenetriamine gives the prod~ct as a salt with 2.4 equivalents of hydrogen chloride solvated with 1.4 equivalents of water and 0.2 eciuivalent of 2-propanol; mp 80~90C
(decomposition~O

7,10-Dihydroxy-2-[2-[(2-h~roxyethyl)amino]ethyl]-5 (4-methyl-1-plperazinyl)anthra[l,9-cd]p~razol-6~2~)-one Reaction with N-methylpiperazine gives the product as a sal~ ~ith 2.2 equivalents o hydrogen chloride solvated with 0O4 equivalent of water and 0.2 equivalent of 2-propanol; mp >123C (decomposition)O
E~AMPLE 65 5-[l2-(Di~ethylamino)ethyl]methylamino]-7,10-di-hydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]anthra-[l,9-cd]-~yrazol-~(2~)-one Reaction with N,N,N-trimethylethylenediamine gives the product as a salt with 2.1 equivalents of hydrogen chloride solvated wi~h l 9 equivalents of water and 0.2 equivalenis of 2-propanol; mp >91C
(decomposition)O
EX~.MPLE 66 5-[12-[(2-~minoetl~vl)amino]etht~]amino]~7,10-di-hydroxy-2-12-[(2-h~droxyethyl)amlno]etht~l]anthra-l,9~cd]-pYrazol-6(2~)-one Reaction wit.h diethylenetriamine gives the product as a salt with l.0 equivalent of 'nydrogen chloride solvated with l.0 equivalent of water, mp 210-215C (decomposition).

3~
CLG-l -112~
EX~PLE 67 5 _ z-[sis(2-hydroxyethyl)amino]ethyl] amino] -7,10-dihydroxy-2-[-2-[(2-hydrox~e~ amlno]ethyl]anthra-[1,9-cd]p~razol-6(2H)-one Reaction with N,N-bi~(2-hydroxyethyl)ethylene-diamine gives the product as a salt with 2.3 equiva lents of hydrogen chloride solvated with 0,8 equivalent of water; mp 230C (decomposition).
EX~MPLE 68 5-1~3-[Bis(2-hydroxyethyl)amino]propyl]amino]-7,10-dihydroxy-2-[2-hydroxyethyl)amino]ethyl]anthra-~l,9-cd]pyrazol-6(2~)-one Reaction with N,N-bis (2-hydroxyethyl) 1,3-propanediamine gives the product as a salt with 2.1 equivalents o~ hydrogen chloride solvaked with l).4 equivalent of water; mp 198-215C (decomposition).

5-~[3-[[4-[(3-Aminoprop~l)amino]butyl]amino3propyl~- -amino]-7,10-dihydroxy-2-[2-[(2-hydroxyethyl)amino]-eth~l]anthra[l,9-cd]~yrazol-6(2H)-one Reaction with spermine gives the product as a ~alt with 2.75 equivalents of hydrogen chloride solvated with 0.6 equivalent of w~ter and 0.1 equiva-lent of 2-propanol; mp 185-Z00C (decomposltion)~
EX~MPLE 70 7,10-Dihydroxv-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-I[2-(methylamino)ethyl]amino]anthra[1!9-cd]- , pyrazol-6(2~)-one Reaction with (2--aminoethyl~-methylcarbamic a~id, benzyl ester followed by isolation o~ the intermediate then hydrolysis with refluxing ~8~
hydrobromic acid in acetic acid gives the product as a salt with 201 equivalents of hydrogen bromide solvated with 2.3 equivalents of water and 0.5 equivalent of acetic acid; mp 222~228C (decomposition).

~2~ 3~
CLG-l -113-2-(2-Aminoethyl)-7~lo~dihydrox~-5-[[z-[(2-hydr ethyl)amino]ethyl~amino]anthra[l,9-cd]pyrazol-6(2H)-one Reaction of a mixture of 2.0 g (6 mmol~ of 2-(2-aminoethyl)-5-chloro-7,10-dihydroxyanthra ~l,9-cd]pyrazol-6(2H)-one, 3 ml (30 mmol) of 2-(2-aminoethylamino)ethanol, and 25 ml of pyridine zt reflux overnight follo~ed 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 -~7ith 2.0 equival~nts of hydrogen chloride solvated with 0.5 equivalent of water; mp 275~28ûC (decomposition).
2-(2-Aminoe~hyl)-5-chloro-1,10-dihydroxyanthra-Il,9-cd3pyrazol~Z(2E~)~one is prepared rom 2-(2-ami-no-ethyl)-5~chloro-7,10-bis(phenylmethoxy)anthr2~1,9-cd]-pyrazol-6(2H)-one and boron trichloride as described in Example 54 to give the product as a-salt with- - -1.0 equivalen~ of hydrogen chloride solvated w-th 0.7 equivalent of water; mp 265-268C tdecomposition).
2-(2-Aminoethyl) -S-chloro-7,10-bis(phenyl-methox~7)anthra[1,9-cd]pyrazol-6(2H)-one is prepared from 1,4-dichloro-5~8-bi~(phenylmethoxy)-9,10-an~hracenedione and (2-aminoethyl)hydrazine as described in Example 54 to give the product; mp 176-178C.

2-(2-1~minoethvl)-5-[(2-aminoethyl)amino~ 7,10--dihydroxyanthra[l~9-cd]pyrazol-6(2H)-one ~ eaction of 2-(2-aminoethyl)-5-chloro-7,10-dihydroxyanthra~l,9-ca]pyrazol-6(2H)-one with ethylenediamine as described in Example 71 gives the product as a salc ~ith 1.9 equivalents of h~rdrogen chloride solvated with 1.0 equivalent of "ater; mp >230C (decomposition).

~:2 5~3~
CLG-l -114-E'~A~PLE 73 2-(2-Aminoethvl)~5-[~3-aminopro~y]~)a~nino]-7 -dihvdroxvanthra[l,9cd]p-~razol-6(2H)-one Reaction of 2-(2-aminoethyl)-5-chloro-7,10-dihydroxyanthrall,9-cd]pyrazol-6(2H~-one w~th 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)O
~ XAMPLE 74 2-~2-Aminoethyl)-5-[[2-[[2-(dimethylamino)ethYl]-amino]ethyl]amino]-7,10-dihvdroxyanthra[l,9-cd]-pyrazol-6t2H)-one Reaction of 2-(2-aminoethyl~-5-chloro-7,10-dihydroxyanthra~l,9-cd]pyrazol 6(2H)-one with N,N-dimethyldiethylenetriamine as described in Example 71 gives the product as a salt with 3.3 equivalents o hydrogen chloride solvated wit~ 1.0 equiJalent of water and 0.2 e~uivalent of 2-propanol;
mp 245-260C (decomposition)O
EXA.~PLE 75 2-(2-Aminoethyl)-5-[[3-[(2-hvdroxyethyl)amino]propyl~-amino]-7~lo-dihydroxyanthratl~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 th~ product as a ~alt with 2.1 equiv~lents o hydrogen chloride solvated with 1.0 equi~alent o water and 0.2 equivalent o 2-propanol; mp 175C
(decomposition).

7,10-Dihydroxy-5-[[2-[(2 hydroxyethyl)amino]ethyl~-amino]-2-12-methoxyethyl)anthra[1,9-cd]pyrazol-6(2H)-one Reaction of a mixture of 2~0 9 (5.8 mmol) of 5-chloro-7,10-dihydroxy~2-(2-methoxyethyl)anthra-4~
CLG-l -115-[1,9-cd]pyrazol-6(2H)-one, 5.8 ml (58 mmol) of 2-(2-aminoethylamino)ethanol, and 25 ml of pyridine at 85OC overnight ~ollowed by wor~up as described in Example 21 gives 1.75 g of product. Salt formation as described in 2xample 3 gives 1.91 g o~ product as a salt with 1.1 equivalents of hydrogen chloride solvated with 0.3 equivalent o~ water and 0.~ equivalent of 2-propanol; mp 68-72C.
~ -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-chloro-2-(2-methoxyethyl)-7,10-bis(phenylmethoxy)anthra-[l,9-cd]pyrezol-6(2H)-one, 91 ml of a 1 M solution of boron trichloride~ and 46 ml of dry dichloromethane zs described in Example 24 gives 6.25 g of the dried product; mp 137 145C ~decomposition1O
5-Chloro-2-(2-methoxyethyl)-7,10-bis(phenyl-methoxy)anthrall,9-cd~pyrazol-6(2H)-one-is--prepared-~-~s follows:
An ice-cold mixture of 3.2 g (6 mmol) of 5-chloro-2-(2-hydroxyethyl)-7,10-bis(phenyl-methoxy)anthra~l,9-cd]pyrazol-6(2H)-one, 1.23 ml (20 mmol~ of iodomethane, and 20 ml o~ N,N-dimethyl-formamide is treated gradually with 0.18 g (8 mmol) of sodium hydride. The ice bath is removed and the mixture is stirred for two hours, treated with five drops of glacial ace~ic acid, then diluted with water.
The solids are filtered, washed sequentially ;~ith 2-propanol and die~hyl ether to give 2.8 g o~ ~he dried product; mp 174-178C~

5-[(2-Aminoethvl)amino] 7,10-dihvdroxy-2-(2-methoxy-__ _ ethyl)anthra[l,9-cd]pyrazol-6(2H)-one ~ eaction of 5-chloro-7,10-dihydroxy-2-(2-methoxy-ethyl)anthra[l,9-cd]pyrazol-6(2H)-one with ethylene-diamine as described in Example 76 gives the product ) ~s~
CLG~
as a salt with 1 0 equivalen~ o~ hydrogen chloride solvated ~ith 0.3 e~uivalent of ~ater, mp 263-268~C
(decomposition)~
EX~MPLE 7~
2-(Z,3-Dih~dro~ypropyl)-7,10-dih~ldrox~L-5-~2-1(2-hydroxvethyl)amino]ethYl]amino~anthra~l,9~cd]-pyrazol-6(2Hl one A mixture of 1.3 g (2 mmol) 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]pyra~ol-~(2~)-one, 260 mg o Z0~ palladium hydroxide on carbon, and 25 ml of glacial a^etic acid is stirred under an a~mosph~re of hydrogen or two hoursO The mixture is filterzd and concentrat2d ~o a residue which is dissolv~d in methanolic hydrogen chloride~ The mixture i5 stirred at room temperature for two hours and concentrated to a solid which is crystallized from 1:1 methanol:
ethanol to give 0.7 g o~ the product zs a salt with 1.1 equivalents o 'nydrogen chloride solvated with 1.0 equivalent of water; mp >110C1 2-l(2,2-3imethyl-1~3-dioxolan-4-yl)methyl]-5-[[2-~(2-hydroxye~chyl)amino]ethyl]amino-7110-bis(phenyl-methoxy)anthra[l,9-cd]pyrazol-6(2~)-one is prepared as follo~s A mixture o 1.2 g ~2 mmol) of 5-chloro-2--dlr~lethyl-1,3~dioxoian~4-yl)methyl]-7,1~-bis-(phenylrcetho~y)anthra~179~cd]pyrazol-6~2~)~0ne~
~.~ m~ (2~ mmol) of 2-~2~aminoethylamino)ethanol, 17 ml of pyridinef and 0 3 g of anhydrou.s potassium carbonate is stirred at reflux for 42 hours. The mixture is diluted with w~ter and filtered to yive a solid that is purified by silica gel chromatography utilizing 94:5:1 dichloromethane:methanol:triethyl-amine. Concentration o the product ractions ollowed by trituration with 2-propanol gives 730 mg of pure peoduct; mp 206C.

CLG-l -117-5-Chloro-2-[(2,2-dimethyl-1,3-dioxolan-4-yl)-methyl]-7,10-bis(phenylme~hoxy)anthra[1,9-cd]-pyrazol-6(2H)-o~e is prepared as follo-~s:
A mixture of 19.6 g (4C ~nol) of 1,4-dichloro-5~8-bis(phenylmethoxy)-9,10-anthracenedione, 10 g (68 mmol) of 4-(~ydrazinomethyl)-2,2-dimethyl-1,3-dioxolan IA , 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 dim~thylsulfoxide is stirred at 80C for six hours.
The mix~ure 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 utilizing 0~ co 1% methanol in dichloromethane giveC Z g of a solid that is triturated from 2-propanol, then crystallized from toluene to afford 1.8 9 of pure product; mp 184-188C. - -2-[2-(Diethylamino)ethyl]-7-[[2-~(2-hydroxyeth~l)-amino]ethyl]amino~anthra~l,9-cd]py~ol-6~2H)-one Reaction of 2.5 g (i mmol) o~ 7-chloro-2-~2-(di-ethylaminojethyl~anthra[l,9~cd]pyra~ol-6(2H)-one, 7 ml (70 mmol) of 2-(2-aminoethylamino)ethanol, and 20 ml oE p~ridine or 20 hours at reflux followed by workup as described in Example 9 gives 1.6 g of a solid/ mp -`
ln4-107C, af-~er recrystalliza,ion from toluene~ Salt ~orma~ion as described in Example 3 gives 1.6 g oE ~he dried product as a salt with 2.0 equivalents of hydrogen chloride solvated with l.l equivalents of water; mp 212-216C (decomposition).
7-Chloro-2-[2-(diethylamino)e~hyl]anthra[1,9-cd]-pyrazol6(2H)-one is prepared as follows:

CLG-l -118-A mixture of 13.85 g (50 ~nol) of 1,5-dichloro-9,10-anthracenedione~ 13.1 g (100 mmol) of (2~diethyl-aminoethyl)hydrazine, 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 of 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 gives 0.8 g of the dried product as a salt with 1.0 equivalent of hydrogen chloride; mp 272-275C (decomposition).
EX~PLE 80 2-[2-(Diethylamino)ethyl]-7-[[2-(diethylamino)ethyl]-amino]anthra[l,9-cd]pyrazol-6(2H1-one Reaction of a mixture of 2.1 g (6 mmol) of 7-chloro-2-[2 (diethylamino)ethyl]anthra[l,9-cd]pyrazol-6(2H)-one, S ml (36 mmol) of N,~-diethylethylenedi-aminet and 20 ml of pyridine for 28 hours at reflux followed by workup as describ~d 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 e~uivalent of wateri mp 292-294C (decomposition)O

2-~2-[(2-Hydroxvethyl)amino~ethyl]-7-[[2-[(2-hydroxy-ethyl)amino]ethvl]amino]anthra[l,9-cdJpvrazol-6-(2~)-one A mixture of 1~9 g (5 mmol) of 7-chloro-2-~2-[~2-hydroxyethyl)amino]e~.hyl]anthra[l9g-cd3pyrazol~6(2H~-one, 2.0 ml (20 mmol) of 2-(2-aminoethylamino~ethanol, ~ and 20 ml of pyridine is heated at reflux for 72 hours. The mixture is cooled, concentrated, and chromatographed over silica gel with O.S~
triethylamine in dichloromethane, utilizing a gradient elution of 2-10~ methanol, to give the product. Salt formation as described in Example 3 gives S00 mg ef CLG-l -119-the product as a salt ~ith 2.0 equivalents of hydrogen chloride sol~ated wlth 0.4 equi~alent of water;
mp 285-287C (decornposition) 7-Chloro-2-[2-[(2-hydroxyethyl~amino3ethyl]-anthra[l,9-cd]pyrazol-6(2H)-one is preoared as follows:
A mixture of ll.l g (40 mmol) of 1,5-dichloro-9,10-anthracenedione, 13.1 g (llO mmol) of 2-t(hydrazinoethyl)amino]ethanol, 4 g of anhydrous potassium bicarbonate, l g of anhydrous potassium ~luoride, and llO ml of dimethyl sulfoxide is stirred at 70C overnight. The mixture is chilled and the solids are collected by filtration, washed with water, th~n thoroughly with acetoni-~rile to give a residue that is crystalliz~d from 2-propanol to leave 2.6 g o~ product. The hydrochloride salt is prepared as described in Example 3; mp 272-273C (decomposition).
E~MPLE 82 7,10-Dichloro-2-~2-[t2-hydroxyethyl~amino]ethvl]
5-[[2-[(2-hydroxyethyl)amino~ethyl~amino]anthra-[l,9-cd~pYrazol-6(2H)-one Reaction of 7,10-dichloro-2-[2-[(2-hydroxy-ethyl)aminolQthyl]-5-[[(4-methylphenyl)sulfonyl]-oxy~anthra[l,9-cd]pyrazol-6(2H)-one, hydrochloride, wlth 2-(2-aminoethylamino)ethanol gives the product.
7,10-Dichloro-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-¦[(~-methylPhenyl)sulfonyl]oxy]anthra[l,9-cd]-pyrazol-6(2~)-one is prepared as follo~s^
To a suspension of 30.9 9 (50 mmol) of 19~-dichloro-5,8-~is[[(4-methylphenyl)sulfonyl]oxy]-9,10-anthracenedione, 13 ml (75 mmol) of N,N-diisopropylethylamine, and 130 ml o ~,N-dimethylformamide at 5C is added dropwise 14.9 g (125 mmol) of 2-[(hydrazlnoethyl)a~ino]ethanol in 70 ml of ~,N-dimethylformamide. The mixture is allowed CLG-l -120~
to reach 10C duriny five hours, then is diluted ~ith 20 ml of acetone. Af~er warming to room temperature, the solution i5 concentrated to an oil that i~
distributed bet-~een water and dichloromethane.
Concentration of ~he dried dichlorome~hane layer follo-~ed by salt formation as described in E%ample 3 gives 18.1 g of the dried product as the hydrochloride sa~t; mp 158-160Co 1,4-Dichloro-5, 8-bis [ ~ ( 4-methylphenyl)sulfonyl]-oxy~-9,10-anthracenedione is prepared as follows:
A mixture of 9.3 g (30 ~mol) of 1,4-dichloro-5,8-dihydroxy 9,10-anthracenedione, 12.6 g (66 mmol) of ~-toluenesulfonyl chloride, 12.2 ml ~70 mmol) o~
N,N-diisopropylethylamine~ and 120 ml of acetonltrile i~ hea~ed at 70C for one hour~ then cooled The crystals are collect~d by filtration to leave 14~4 g of dried product; mp 195.5-196O5C. Processing of the filtrates.gives 2~2.g.of..additional product~
mp 19~-192C~ .
EX~MPLE 83 7-~ydroxy-2-[2-[(2-hydroxyethyl)amino]ethyl]-5-~2-~(2-hydroxyethyl)amino]ethyl]amino]anthra[1,9-cd]
pyrazol-6(2~)-one Reaction of a mixture of 2-[2-1(2-hydroxyethyl) amino]ethyl]-5-[[2-[(2-hydroxyethyl~amino]ethyl]-amino]-7-(phenylmethoxy)anthra~l,9-cd]pyrazol 6(2H)-one with hydrogen and 20~ palladlum hydroxide on ~arbon as ~escribed in Example 78 giv~s the product as ~ 5al~ with 2.0 equivalent~ oE hydrogen chloride solYated with 2.3 equivalents of water, mp 265-270C
~decomposition).
2-12~[(2-hydroxyethyl)amino~ethyl]-5-[[2-[(2-hydroxye~hyl)amino]e~hyl]amino-7-(phenylmethyoxy) anthra[l,9-cd]pyrazol-6(2H)-one is prepared as f ollows:
Reaction of 5-chloro-2-[2-[(2-hydroxyethyl)-an~.ino3ethyl]-7~(phenylmethoxy)anthra[1,~-cd~pyrazol-CLG-l -121-6(2H)-one with 2~(2-aminoethylamino)etha~ol as described in E~ample 78 yives the product;
- mp 157-159C.
5-Chloro-2-[2-1(2-hydroxyethyl)amino~ethyl]-7-(phenylmethoxy~anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
A mixture of 4.2 g (11.0 m~ol) of 1,4-dichloro-5-(phenylmethoxy)-9,10-anthrace~edione, 2.6 g (22.0 mmol) of 2-~(hyrazinoethyl)amino~ethanol, 320 mg (5.5 mmol) of anhydrous potassium fluoride, 1.1 g (11.0 mmol) of anhydrou5 potassium bicarbonate, and 33 ml of dimethyl-sulfoxide is stirred overnight at 80C~ The mixture is cooled and poured into water. The aqueous mixture is centriuged and the aqueous phase is decanted to leave an oil that is dried and purified on silica gel utilizing 4:1 dichloromethane:methanol as eluting solvent~ Concentration of the product fractions ~ollowed by tritura-tion from-methanol gives 84~-~g ~~~
o the dried product; mp 141-145C.
1,4-Dichloro-5-(phenylmethoxy)-9,10~anthra-cenedione is prepared as follows:
A mi~ture of 5~33 g (18 mmol) of 1,4-dichloro-S-hydroxy-9,10-anthracenedione (British Pat~nt 1,029~448), 2~6 g (19 mmol) of powdered anhydrous potassium carbonate, 2~5 ml (21 mmol) of ben~yl bromide, ~nd 75 ml of dry acetone is heated at re~lux overnight The mixture is cooled and the solids are washed well with acet~ne.
Concentra~ion of -~he ~iltrates gires a solid which is triturated with ether to afford 5.8 g of the dried product; mp 118-1~2~C
Prepared in a fashion s~milar to Example 83 is the following~

3~S~;~39 CLG-l -122~
2X~MPLE 84 7-Hydroxy~2-[2-[(2-hvdrox~et~y~-aminoJethyl)-5-[[2-(methylamino)ethyl~amino]anthra[l,9-cd]pyrazol-6(2H)-one as a salt with 1,8 equivalents of hydro~en chloride sol~ated with 1.2 equivalents o ~ater, - mp 280-282C (decomposition) is prepared from 2-[2-[(2-hydroxyethyl)amino]ethyl]-5-[[2 [methyl(phenyl-methyl)amino]ethyl]amino]-7-(phenylmethoxy)anthra [1~9-cd]pyrazol 6(2~)-one; mp 110-113~C, which is prepared ~rom the reaction of N-methyl-N-(phenyl-methyl)-1,2-ethanediamine (US Patent 3,201,459) with 5-chloro-2-[2-[(2-bydroxyethyl)amino]ethyl]-7-(phenyl methoxy)anthra~l,9-cd]pyrazol-6(2H)-one, EX~MPLE 85 10-Hydroxy-2~[2-[~2-hydroxyethyl)amino]ethyl]-5-[[2-~(2-hydroxyethyl)amino]ethyl]amino]a-nthra [l,9-cd]-pyrazol-6(2H)-one Reaction of a mixture. .o~..2-.E2-~(2-hyaro~y~thyl)-.
amino]ethyl]-5-~[2- E ( 2-hydroxyethyl)amino~ethyl] .
amino]-lO~(phenylmethoxy)anthra[1,9-cd]pyrazol-6(2H)-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 ~ater; mp 260-267C
(decomposition)O
2-[2-[(2-hydroxyethyl)amino3ethyl]-5-[[2~[(2-hydroxye~hyl)amino3e~.hyl~amino 10 (phenylmetXoxy)-anthra~l,9-cdlpyrazol-6(2EI~-one is p~epared a~
follaws~
Reaction of 5-chloro 2-[2-L(2-hydroxyethyl) amino]-ethyl]-10-(phenylmethoxy)anthra~1,9 cd]pyrazol-6(2H)-one with 2 (~-aminoethylamino)ethanol as described in 2xample 78 gives the product;
mp 178-180C.
5-Chloro-2-~2-[(2-hydro~yethyl)amino]ethyl]-10-(phenylmethoxy)2nthra[1,9-cd]pyrazol-6(2H)-one is prepared as follows:

~lZ~ 3~
CLG-l -123-Reaction of 1,4-dichloro-5-(phenylmethox~)-9,10-anthracenedione wi~h 2-[(hydrazinoethyl)amino]ethanol as described in Example 83 gi~es the product as the minor isomer; mp 165-167C.

?, 9, 10-Trihydroxy-2-[2-[(2-hyd~ox~ethyl_am no]ethyl]-5-[[2-[(2-hydroxyetnyl)amino~ethyllamino]anthra~
[l,9-cd¦-p~razol-6(2H)-one Reaction of a solution of 2-[2-[(2-hydroxyethyl)-amino]ethyl]-5-[[2-[(2-hydroxyethyl)amino]ethyl]-aminol-7,9,10-tris(phenylmethoxy)anthra[1,9-cd]-pyrazol-6(2H)-one in glacial acetic acid with hydrogen 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 eyuivalent of water; mp > 235C (decomposi~ion)~
2-[2-[(2-Hydroxyethyl)amino]ethyl]-5-[[2-[(2-~_ hydroxyethyl)amino~ethyl]amino]-7,9,10-tris(phenyl-methoxy)anthra[l,9-cd]pyra~ol-6(2~)-one is p.eparea as follows:
A mixture of 660 mg (1 mmol) of 5-chloro-2-[2-t(2-hydroxyethyl)amino]ethyl]-7,9,10-tris (phenyl-methoxy~anthra[l,9-cd]pyrazol-6(2H)-one, 1 ml (10 mmol) of 2-(2-aminoethylamino)ethanol~ and 2 ml o pyridine is heated at reflux for 28 hours. Workup as described in Example 21 gives a solid whose crystallization from acetonitrile chloro-orm affords 30~ mg of product; mp 158-159C.
5-Chloro-2-[2-[(2-hydroxyethyl)amino~ethyl]-7,9,10-t-ris(pnenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)~
one is prepared as follows:
A suspension of 7.2 g (12 mmol) of 5,8-dichloro-1,2,4-tris(phenylmethoxy)-9,10-anthracenedione, 209 g (24 mmol) of 2-1(hydrazinoethyl)amino]ethanol, 350 mg (6 mmol) of anhydrous potassium flouride, 1.2 g (12 mmol) of anhydrous potassium bicarbonate, and 25 ml of dimethylsulfoxide is stirred overnight at !

~25;~i~3~
CLC~ 124-75C. The mixture is cooled7 then triturated wi'ch ~-propanol. The solids are filtered, ~ashed ~ell ~ith water, 2-propanol, ~hen crystallized from chloro-form to give 2.3 g of orange solid; mp 172-173C.
2rocesslng of ~he nonaqueous filtrates yi~7es 640 mg of additional product corresponding to caO 1:1 mlxture of isomers by 1~ ~IR; ~p 135-140~C, 5,8-Dichloro-1~2,4-tris(phenylmethoxy)-9,10-anthracenedione is ~repared is as follows~
A suspension of 7.5 g (23 mmol) of 5,8-dichloro-1,~,4-trihydroxy-9,10-anthracenedione, 9.6 ml ~81 mmol~ of benzyl bromide~ 9O9 g (72 mmol) of powdered anhydrous potassium carbonate, 0,4 ~1 of methanol/ 92 ml of acetone, and 46 ml of ~,N-dimethylfo-rmamide is heated at. reflux under argon for two days. An additional 2.7 ml of benzyl ~romide is added and the mixture is heated for three daysO
The suspension is filtered and--the filtrate is~
concentrat2d to an oil which i5 distributed betwee~
dichloromethane and 10% aqueous acetic acid. The dried dichloromethane layer is concentrated to a solid whose crystallization from ethyl acetate affords 7~2 g o~ product; mp 174-175Co ~ ,8-Dichlorc-1,2~-trihydroxy-9,10-anthracenedione is prepared as Eollows A ~uspension of 451 mg (1 ~mol) of 1,29 4-tris (ace~ylox~)-5,8-dichloro-9710-anthracenedioneJ S ml o glacial acetic acid; and 5 ~nl of 6 N aqlleous hydro-chloric acid is heated at 70~ for one hollr~ Ths suspension is cooled and the solids are filtered off.
Af~er washing with water and drying, there remains 2~7 mg oE the dried product; mp 290-295C
(decomposition)u 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 i .

~s~
CLG-l -125-acid, and 10 ml of acetic anhydride is s~irred at room temperature for 30 minutes. The solution is diluted with water, the organic layer is separated, and dried, then concentrated to a solid residue.
Trituration of the solid from ethyl acetate lea~es 235 mg of product; mp 205-206C.
5,8-~ichloro-1,4,9,10-anthr2cenetetrone is prepared as follows;
A suspension o 618 mg (2 mmol~ of 1,4-dichloro-5~8-dihydroxy-9~10-~nthracenedione, 1.06 g (2.4 mmol) of lead tetraacetate, and 25 ml of glacial acetic acid is stirred at room temperature for 45 minutes~ The mixture is treated with 0.5 ml ethylene glycol, and a~ter 15 minutes is diluted with dichloromethane.
The mixture is washed wi~h water and ths dried organLc layer is evaporated to a solid. Trituration of the solid from diethyl ether ~ives 569 mg of product;
mp 255-257~ (decompGsition)-.-~
EX~MPLE 877,8,1G-Trihydroxy-2-[2-~(2-hydroxethyl)Gmino~ethyl]-5-l[2-[(2-hydroxyethYl)amino]ethyl]amlno]anthra-~l,9-cd]pyra7O1-6(2H)-one Reaction of a solution of 2-[2-[(2-hydrox~ethyl)-amino~e-thyl]-5-[[2-[(2-hydroxyethyl)amino]ethyl]
amino]-7,8,10-tris(phenylmethoxy)anthra[l,9-cd~-pyrazol-5(2 )-one in glacial acetic acid with hydrogen and 20% palladium hydroxide on carbon as described in Example 78 gi~es the product as a salt with 2~1 equi~7alents oE hydrogen chlorlde solvatecl with 0.
equivalent of ~ater; mp >210C (decomposition)~
2-[2-[(2-Hydroxyethyl)a~ino]ethyl]-5-[[2-[(2-hydroxyethyl)amino]ethyl]amino]-7,8,10-tris(phenyl-methoxy)anthra[l,9-cd]pyrazol-6(2~)-one is prepzred as follows:
Reaction of 5-chloro-2-[2~[(2-hydroxyethyl)-amino]ethyl]-7,8,10-triq(phenylmethoxy)anthra[1,9-cd]-.. , B3~
CLG-l -126-pyrazol-6(2H)-one with 2-(2-aminoethylamino)ethanol as described in Exa~ple 86 gives the pro2uct;
mp 186-188C.
5-Chloro-2-~Z-[(2-hydroxyethyl)amino]ethyl~-7,8,10-tris(phenyl~ethoxyjanthra[l,9-cd]pyrazol-6(2H)~one is prepared as follo~5:
Reaction of 5,8-dichloro-1,2,~-tris(phenyl-methoxy)-9,10-anthracenedione with 2-[(hydrazino-ethyl)amino]ethanol as described in Example 86 gives the product as the minor isomer; mp 164-167~C~
Prepared in a fashion similar ~o Exam21e 87 is the following:
E~AMPLE 88 7,8~10-Trihydro~y-2-[2-[(2-hydroxyethyl)amino)]ethyl]
5-C[2-(methylamino)ethyl]amino]anthra~1,9-cd]~
pyra2O1-6(2H)-one as a salt with ~.0 equivalents of hydrogen chloride solvated with 0.7 equivalent of water; mp >220C (decomposition~, which is prepared from 2-[2-[(2-hydroxyethyl)amino]ethyl~-5-t[2-[methyl(phenylme~hyl)amino]ethyl]amino]-7,8,10-tris (phenylmethoxy)anthra[1,9~cd]pyrazol-6(2H)-one;
mp 104-~108C which is prepared from the reaction of N-methyl-N(pn~nylmethyl)-1,2-ethanediam~ne with 5~chloro-2-[2-l(2~hydroxyethyl)amino]ethyl~
7,8,10-tris(phenylmethoxy)anthra~l/9-cd]pyrazol-G(2~)-one~
EXA~2LE 89 5-[~2-[(2-Aminoe-~hyl)amino~etnyl~amino]-7,10 dihydroxt~-2-(2-nydroxyethyl)a~hra[1,9-cd]-pyrazol-6(2H)-one Reaction of a 5olution o 5-[[2-[(2-aminoethyl)-amino]e~hyl]amino-2-(2-hydroxyethyl)-7,10-bis(phenyl-metho:sy)anthra[l,9--cd]pyrazol-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 salt with 2.4 equivalents of hydrogen chloride solvated with 0.8 equlvalent of water; mp 170-1~5~C
(decomposition).

CLG-l -127~
5-[[2-[(2-Aminoethyl)amino]ethyl]amino-2-(2-hydroxyethyl)-7 10-bis(phenylmethoxy)anthra[l 9-cd~-pyrazol-6(2H)--one is prepared as follows:
A mixture of 5 1 g (10 mmol) of 5-chloro-2-(2-hydroxyethyl)-7~lo-bis(phenylmethoxy)anthra[l~9-cd pyrazol-6(2H)-one 10 g (100 mmol) of diethylene-triamine~ 1.4 g (10 mmol) of anhydrous potassium carbonate and 60 ml of pyridine is heated a~ reflux for 28 hours. The mixture is cooled 7 the solids are collected by filtration then washed seque~tially with water and 2-propanol to give 3.1 9 of the product;
mp 185-190C.

2-~3-Aminopropyl)-7~10-dihydroxy-5-[[2-[(2-hydroxy ethyl)ami}lo]e~hvl~aTnino]anthra[l,9-cd]~Yrazol-~(2H)-one Reaction of a solution of 1~2 g (2 mmol) of - -2-t3-aminopropyl)-5 ~2- E-( 2-hydroxyeth~l)amino3ethyl~~
amino]-7 10-~is(phenylmethoxy)anthra[l 9-cd~pyrazol-6(2H)-one in glacial acetic acid with hydrogen and 20 palladium hydroxide on carbon as described in Example 7~ ollowed by salt formatlon as described in Example 3 gives 8~0 mg of ~he product a salt with 2.0 equi-valents o hydrogen chloride solvated wi~h 1.1 ~qui-valents of water; mp 292-294C (decomposition)0 2-(3-Aminopropyl)-5-[[2-[(2-hyroxyethyl)amino]-ethyl]amino-7,10-bis(phenylmethoxy)anthra[1~9-cdJ-pyrazol-6(2a)~one is prepared as follows.
A mixture of 530 mg (1 mmol~ oE 2-(3-amino-propyl)-5-chloro-7 10-bistphenylmethoxy)anthra-1 9-cd3pyrazol-6(2H)-one 1 ml (10 mmol) of 2-(2-aminoethylamino)ethanol 140 mg (1 mmol) of anhydrous potassium car~onate and 8 ml oE pyridine is heated at reflux or 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[l 9-cd]pyrazol-6(2~)-one is ) prepared as follows:

25~3~L
CLG-l -128-Reaction oE a mixture o~ 1,4-dichloro-5,8-bis~
(phenylmethoxy)~9,10-anthracenedione and (3-amino-propyl)hydrazine [Helvetica _ himica Acta 4Z; 533 (1959)] as described in Example 54 gives the product;
mp 180-18~C.
Prepared in a fashion similar to Example 90 i5 the ollowing:

2-53-Aminopropyl)-5-[[2-[[2-(dimethylamino)ethyl]-amino ~ amino]-7,10-dihydroxy---thra[l;9~cd]
pyrazol-6(2H)-one as a salt with 3.0 equivalents of hydrogen chloLide solvated with 2.0 equivalents of water; mp 294C (decomposition), which is prepared froln 2 (3-aminopropyl)-5-[[~-[[2 (dimeth.ylamino)-ethyl]a~ino]ethyl]amino]-7,10-bis(phenylmethoxy) anthra[l,9-cd]pyrazol-6(2H)-one; mp 143-160C, which - is prepared from the reaction OL N,N-dimethyldi-e.hylene~riamine with 2-(3-aminopropyl)-5-chloro-7,10-bis(phenylmethoxy)anthra[l,~-cd3pyrazol-~(2H)-one.

2-(2-Aminoethyl)-7,10-dihydroxy- _ [[2-(methylamino)-ethyl]amino]anthra[l,9-cd]pxrazol-6(2 ?-one Reaction of a mixture of 2-(2-a~inoethyl)-5-1[2-methyl(phenylmethyl)amino]ethyl]amino]-7rlo-bi (phenylmethoxy)anthra~l,9-cd]pyrazol-6~2H)-one with hydrogen and 20~ palladium hydroxide on carbon as - described in Example 78 giYeS the ~roduct as a salt with 2~2 equivalents of hydrogen chloride solvated with 0.5 equivalent of water; mp 259-264C
(decomposition).
2-(2-Aminoe~hyl)-5-[[2-[methyl(phenylmethyl)-amino3ethyl3amino]-7,10-bis(phenylmethoxy)anthra[l,9-cd~pyrazol-6(2~)-one i5 prepared as follows:
Reaction of 2-(2-aminoetnyl)-5-chloro-7,10-bis-(phenylmethoxy)anthra[l,9-cd]pyra~ol-6(2H)-one ~ith ?

CLG-l -129-N-methyl-~-(phenylmethyl)-1,2-ethanediarnine as de-scribed in Example 7a gives the product; mp 169-172~C.
EXA.~PLE 93 7~10-Dihydroxy-5-[[2-[(2-h~!droxyethyl)amino]ethyl]-amino]-2-[2-(methyiamino)ethyl]anthra[l,9-cd]pyrazol-6(2H)-one Reaction of a mixture of 5-~[2-~(2-hydroxyethyl)-a~ino]ethyl]amino]-2-[2-(methylamino)ethyl]-7,10-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 as a salt with 2.0 equivalents of hydroyen chloride solvated with 1.8 equivalents of wa~er; mp 180-185C
(decomposition)O
5-112-~(2-hydroxyethyl~amino]ethyl]amino3-2-[2-(methylamino)ethyl]-7,10-bis(phenylmethoxy)anthra-[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
Reaction of 5-chloro-2-r2-(methylamino)ethyl]- - ~
7,10-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one with 2-(2-aminoethylamino)ethanol as described in Example 78 gives thP 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:
Reaction of 5-chloro-2-[3-[[4-methylphenyl)-sulfonyl]oxy]ethyl]-7,10-bis(phenylmethcxy)anthra-[l,9-~d~pyrazol-6(2H)-one with methylamine as de-scribed in Example 51 gives the product; mp 171-176C.
EX~MPLE 94 5-~(2-A~inoethvl)amino]-2-~3-(dimethYlamino)propyl]-7,10-dihydroxyanthra[l,9-cd]pyrazol-6(2H~-one -~ eaction of S-chloro-2-[3-(dimethylamino)propyl]-7,10-dih~ydroxyanthra[l,9-cd]pyrazol-6(2H) one, hydro-chloride, with ethylenediamine as described in Example 46 glves the product as a salt with 2.0 equivalents of hydrogen chloride solvated with 0.5 equivalent ~2~ 3~
CLG-l -130-of water and 0.1 equivalent of 2-propanol; mp 316C
(decomposition).

7,8-Dihydroxy-2-[2-[(2-hydroxvethyl)amino]ethy1]-5-[~2-[(2-hydroxyethyl)amino]e~y~amino]anthra[l!9-cd]
pYrazol-6(2H)-one Reaction of a mixture of 2-[2-[(2-hydroxyethyl)-amino]ethyl]-5-[[2-[(2-hydroxyethyl)amino~ethyl]-aminoj-7,8-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2~)-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]ethyl~amino]-7,8-bis-(phenylmethoxy)clnthra[l,9-cd]~yrazol-6(2H)-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-aminoethylamino)ethanol as described in Example 78 gives the product.
5-Chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]-7,8-bis(phenylmethoxy)anthra[l,9-cd]pyrazol-6(2H)-one is prepared as follows:
Reaction of 1,4-dichloro-5,6-bis(phenylmethoxy)-9,10-anthrâcenedione with 2-[(hydra~inoethyl)amino3-ethanol as described in ~xample 54 gives the product.
1,4-~ichloro-5,6-bis(ph~nylmethoxy)-9,10-anthracenedione is prepared as follows:
Reaction of 1,4 dichloro-5,6-dihydroxy-9,10-anthracenedione with benz~l bromide as described in Example 48 gives the product.
1,4-Dichloro-5,6-dihydroxy-9,10-anthracenedione is prepared as follows:
Reaction of nitrosyl sulfuric acid and 5,6-diamino-1,4-dichloro-9,10-anthracenedione [~him.
Geterotsikl~ Soedln. 808 (1968)] gives the product.

Claims (6)

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:

(IV) wherein:
R represents a group selected from H and C1-6alkyl;
Y represents a group selected from H, C1-6alkyl, OR1-substituted-C1-6alkyl and -ANR2R3, wherein:
R1 is as defined above for R, A represents C2-8alkylene, and R2 and R3, independently, represent a group selected from H, C1-6alkyl, OH-substituted C1-6-alkyl, and N(Ra)2-substituted-C1-6alkyl, wherein Ra represents a group selected from H, C1-3alkyl and OH-substituted-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
1. Claim 1 contd. 2 -N(R4)-, wherein R4 is as defined above for R; or R and Y, when taken together, represent a group selected from -CH2CH2- and , wherein m, n and B are as defined above; and Z represents a group selected from H, C1-6alkyl, OR1 substituted-C1-6alkyl, SR1-substituted-C1-6alkyl, -N(R1)2-substituted-C1-6alkyl and -DNR2R3, wherein R1, R2 and R3 are as defined above and D represents a group selected from C2-8alkylene and OH-substituted-C2-8-alkylene;
   with the provisos:
   (i) when Z represents H, R and Y, when taken together, do not complete a piperidine ring; and (ii) when Z represents -CH3, R and Y, when taken together, do not complete a piperidine or morpholine ring;
   said process comprising:
   (a) reacting a compound of general formula:
   
   (VII) wherein Z is as defined above, with an amine of general formula HNRY, wherein R and Y are 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. 2. A compound of general formula:
   
   ( IV) wherein:
   R represents a group selected from H and C1-6alkyl;
   Y represents a group selected from H, C1-6alkyl, OR1-substituted-C1-6alkyl and -ANR2R3, wherein:
   R1 is as defined above for R, A represents C2-8alkylene, and R2 and R3, independently, represent a group selected from H, C1-6alkyl, OH-substituted C1-6-alkyl, and N(Ra)2-substituted-C1-6alkyl, wherein Ra represents a group selected from H, C1-3alkyl and OH-substituted-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 R; or R and Y, when taken together, represent a group selected from -CH2CH2- and , wherein m, n and B are as defined above; and Z represents a group selected from H, C1-6alkyl, OR1-substituted-C1-6alkyl, SR1-substituted-C1-6alkyl, N(R1)2-substituted-C1-6alkyl and -DNR2R3, wherein R1, R2 and R3 are as defined above and D represents a group selected from C2_8alkylene and OH-substituted-C2_8-alkylene;
   with the provisos:
   (i) when Z represents H, R and Y, when taken together, do not complete a piperidine ring; and (ii) when Z represents -CH3, R and Y, when taken together, do not complete a piperidine or morpholine ring;
   and a pharmaceutically acceptable salt thereof.
3. 3. 2-[2-(Diethylamino)ethyl]-7-[[2-[(2-hydroxyethyl)-amino]ethyl]amino]anthra[1,9-cd]pyrazol-6(2H)-one, and a pharmaceutically acceptable salt thereof.
4. 4. 2-[2-(Diethylamino)ethyl-7-[[2-(diethylamino)-ethyl]amino]anthra[1,9-cd]pyrazol-6(2H)-one, and a pharmaceutically acceptable salt thereof.
5. 5. 2-[2-[(2-hydroxyethyl)amino]ethyl]-7-[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthra[1,9-cd]pyrazol-6-(2H)-one, and a pharmaceutically acceptable salt thereof.
6. 6. A pharmaceutical composition comprising a compound of general formula (IV) as defined in claim 2, 3 or 4, and a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.