Disclosed herein are compounds referred to as "fused pyrrolocarbazoles" which possess a variety of functional activities. The disclosed compounds are represented by the following general formula: ##STR1## Methodologies for the synthetic production of fused pyrrolocarbazoles are also disclosed, as well as exemplary uses of the compounds.

BACKGROUND OF THE INVENTION 
Publications cited throughout this disclosure are incorporated herein by 
reference. 
The microbial-derived material referred to as "K-252a" is a unique compound 
which has gained significant attention over the past several years due to 
the variety of functional activities which it possesses. K-252a is an 
indolocarbazole alkaloid that was originally isolated from a Nocordiosis 
sp. culture (Kase, H et al. 39 J. Antibiotics 1059, 1986). K-252a is an 
inhibitor of several enzymes, including protein kinase ("PKC") and trk 
tyrosine kinase. The reported functional activities of K-252a are numerous 
and diverse: tumor inhibition (U.S. Pat. Nos. 4,877,776 and 5,063,330; 
European Publication 238,011 in the name of Nomato); anti-insecticidal 
activity (U.S. Pat. No. 4,735,939); inhibition of inflammation (U.S. Pat. 
No. 4,816,450); treatment of diseases associated with neuronal cells (WIPO 
Publication WO 94/02488, published Feb. 3, 1994 in the names of Cephalon, 
Inc. and Kyowa Hakko Kogyo Co., Ltd.). 
The reported indolocarbazoles share several common attributes: in 
particular, each comprises three five member rings which all include a 
nitrogen moiety; staurosporine (derived from Streptomyces sp.) and K-252a 
(derived from Nocordiosis sp.) each further comprise a sugar moiety linked 
via two N-glycosidic bonds. Both K-252a and staurosporine have been 
extensively studied with respect to their utility as therapeutic agents. 
The indolocarbazoles are generally lypophilic which allows for their 
comparative ease in crossing biological membranes, and, unlike 
proteinaceous materials, they manifest a longer in vivo half life. 
While K-252a possesses such varied and useful activities, a drawback to the 
compound is that because it is of microbial origin, it must be derived 
from culture media via a fermentation process; the literature indicates 
that K-252a has never been chemically synthesized. Accordingly, compounds 
which possess the desired functional activities of K-252a but which can be 
readily derived using chemical synthesis techniques would offer several 
unique and distinct advantages over the types of carbazole compounds 
currently available to the art. 
SUMMARY OF THE INVENTION 
Disclosed herein are synthetic, organic small molecule compounds which are 
biologically active and which we refer to as "fused pyrrolocarbazoles." By 
"synthetic" we mean that the disclosed molecules are chemically 
synthesized de novo; the indolocarbazole K-252a is a "natural" compound in 
that it must be initially derived via a fermentation process, followed by 
isolation and purification. 
Unlike the indolocarbazoles, our novel fused pyrrolocarbazoles comprise a 
unique "E" ring which does not include nitrogen at the 12-position (the 
alphabetical ring designations set forth in Porter, B and Ross C. 57 J. 
Org. Chem. 2105, 1992, are utilized for reference purposes). Additionally, 
the fused pyrrolocarbazoles do not include a sugar moiety linked via two 
N-glycoside bonds. Because our compounds do not include such a sugar 
moiety, synthetic production can be readily achieved. Beneficially and 
surprisingly, our unique compounds, which are not of microbial origin, can 
be readily synthesized and possess a variety of diverse and selective 
biological activities which allows for a broad range of applications 
heretofore only observed with certain indolocarbazoles. 
Fused pyrrolocarbazoles as disclosed herein are represented by the 
following general formula: 
##STR2## 
Constituent members are disclosed in detail, infra. As previously noted, 
in the E ring, constituent "X" is not nitrogen. 
Preferred fused pyrrolocarbazoles are represented by the following 
formulae: 
##STR3## 
Constituent members are disclosed in detail, infra. 
Preferred fused pyrrolocarbazole species are those represented by Formulae 
I, Ia and Ib in Table I, which is presented infra 
Preferred methodologies for the routes of synthetic preparation are also 
disclosed herein, including methodologies for the preparation of 
regiospecific fused pyrrolocarbazole, lactam isomer, and for halogenating 
a fused pyrrolocarbazole. 
We have discovered that our fused pyrrolocarbazoles may be used in a 
variety of ways, including: enhancing the function and/or survival of 
cells of neuronal lineage, either singularly or in combination with 
neurotrophic factor(s) and/or indolocarbozoles; enhancing trophic 
factor-induced activity; inhibition of protein kinase ("PKC") activity; 
inhibition of trk tyrosine kinase activity; inhibition of proliferation of 
a prostate cancer cell-line; and inhibition of the cellular pathways 
involved in the inflammation process. Because of these varied activities, 
the disclosed compounds find utility in a variety of settings, including 
research and therapeutic environments. 
These and other features and advantages of the fused pyrrolocarbazoles will 
be disclosed in the following pages of the patent disclosure.

II. FUSED PYRROLOCARBAZOLES 
Disclosed herein are fused pyrrolocarbazoles represented by the following 
Formulae: 
A. Formula I. 
##STR4## 
wherein: a) A.sup.1 and A.sup.2 together represent O, and B.sup.1 and 
B.sup.2 together represent O; 
b) R.sup.1 is H, alkyl of 1-4 carbons (inclusive), aryl, arylalkyl, 
heteroaryl, and heteroarylalkyl; COR.sup.9, where R.sup.9 is alkyl of 1-4 
carbons (inclusive), or aryl, preferably phenyl or naphthyl; --OR.sup.10, 
where R.sup.10 is H or alkyl of 1-4 carbons (inclusive); --CONH.sup.2, 
--NR.sup.7 R.sup.8, --(CH.sub.2).sub.n NR.sup.7 R.sup.8, where n is an 
integer of 1-4 (inclusive); or --O(CH.sub.2).sub.n NR.sup.7 R.sup.8 ; and 
either 
1) R.sup.7 and R.sup.8 independently are H or alkyl of 1-4 carbons 
(inclusive); or 
2) R.sup.7 and R.sup.8 are combined together to form a linking group of the 
general formula --(CH.sub.2).sub.2 --X.sup. --(CH.sub.2).sub.2 --, where 
X.sup.1 is O, S or CH.sub.2 ; 
c) R.sup.2 is H, --SO.sub.2 R.sup.9 ; --CO.sub.2 R.sup.9, --COR.sup.9, 
alkyl of 1-8 carbons (inclusive), preferably an alkyl of 1-4 carbons 
(inclusive), alkenyl of 1-8 carbons (inclusive), preferably an alkenyl of 
1-4 carbons (inclusive), or alkynyl of 1-8 carbons (inclusive), preferably 
an alkynyl of 1-4 carbons (inclusive); or a monosaccharide of 5-7 carbons 
(inclusive) where each hydroxyl group of the monosaccharide independently 
is either unsubstituted or is replaced by H, alkyl of 1-4 carbons 
(inclusive), alkylcarbonyloxy of 2-5 carbons (inclusive) or alkoxy of 1-4 
carbons (inclusive); and either 
1) each alkyl of 1-8 carbons (inclusive), alkenyl of 1-8 carbons 
(inclusive), or alkynyl of 1-8 carbons (inclusive) is unsubstituted; or 
2) each alkyl of 1-8 carbons (inclusive), alkenyl of 1-8 carbons 
(inclusive), or alkynyl of 1-8 carbons (inclusive) independently is 
substituted with 1-3 aryl of 6-10 carbons (inclusive), preferably phenyl 
or naphthyl; heteroaryl, F, Cl, Br, I, --CN, --NO.sub.2, OH, --OR.sup.9, 
--O(CH.sub.2).sub.n NR.sup.7 R.sup.8, --OCOR.sup.9, --OCONHR.sup.9, 
O-tetrahydropyranyl, NH.sub.2, --NR.sup.7 R.sup.8, --NR.sup.10 COR.sup.9 ; 
--NR.sup.10 CO.sub.2 R.sup.9, --NR.sup.10 CONR.sup.7 R.sup.8, 
--NHC(.dbd.NH)NH.sub.2, --NR.sup.10 SO.sub.2 R.sub.9, --S(O).sub.y 
R.sup.11, where R.sup.11 is H or alkyl of 1-4 carbons, aryl of 6-10 
carbons, preferably phenyl or naphthyl, or heteroaryl and y is 1 or 2; 
--SR.sup.11, --CO.sub.2 R.sup.9, --CONR.sup.7 R.sup.8, --CHO, COR.sup.9, 
--CH.sub.2 OR.sup.7, --CH.dbd.NNR.sup.11 R.sup.12, --CH.dbd.NOR.sup.11, 
--CH.dbd.NR.sup.9, --CH.dbd.NNHCH(N.dbd.NH)NH.sub.2, --SO.sub.2 
N.sub.R.sup.12 R.sup.13, --PO(OR.sup.11).sub.2, or OR.sup.14 where 
R.sup.14 is the residue of an amino acid after the hydroxyl group of the 
carboxyl group is removed; and either 
i) R.sup.12 and R.sup.13 independently are H, alkyl of 1-4 carbons 
(inclusive), aryl of 6-10 carbons, preferably phenyl or naphthyl, or 
heteroaryl; or 
ii) R.sup.12 and R.sup.13 are combined together to form a linking group, 
preferably --(CH.sub.2).sub.2 --X.sup.1 --(CH.sub.2).sub.2 ; 
d) each R.sup.3, R.sup.4, R.sup.5 and R.sup.6, independently is H, aryl, 
preferably an aryl of 6-10 carbons (inclusive), more preferably phenyl or 
naphthyl, heteroaryl; F, Cl, Br, I, --CN, CF.sub.3, --NO.sub.2, OH, 
--OR.sup.9, --O(CH.sub.2).sub.n NR.sup.7 R.sup.8, --OCOR.sup.9, 
--OCONHR.sup.9, NH.sub.2, --CH.sub.2 OH, --CH.sub.2 OR.sup.14, --NR.sup.7 
R.sup.8, --NR.sup.10 COR.sup.9, --NR.sup.10 CONR.sup.7 R.sup.8, 
--SR.sup.11,--S(O).sub.y R.sup.11 where y is 1 or 2; --CO.sub.2 R.sup.9, 
--COR.sup.9, --CONR.sup.7 R.sup.8, --CHO, --CH.dbd.NOR.sup.11, 
--CH.dbd.NR.sup.9, --CH.dbd.NNR.sup.11 R.sup.12, --(CH.sub.2).sub.n 
SR.sup.9, where n is an integer of 1-4 (inclusive), --(CH.sub.2).sub.n 
S(O).sub.y R.sup.9, --CH.sub.2 SR.sup.15 where R.sup.15 is alkyl of 1-4 
carbons (inclusive); --CH.sub.2 S(O).sub.y R.sup.14, --(CH.sub.2).sub.n 
NR.sup.7 R.sup.8, --(CH.sub.2).sub.n NHR.sup.14, alkyl of 1-8 carbons 
(inclusive), preferably alkyl of 1-4 carbons (inclusive); alkenyl of 1-8 
carbons (inclusive), preferably alkenyl of 1-4 carbons (inclusive); 
alkynyl of 1-8 carbons (inclusive), preferably alkynyl of 1-4 carbons 
(inclusive); and either 
1) each alkyl of 1-8 carbons (inclusive), alkenyl of 1-8 carbons 
(inclusive) or alkynyl of 1-8 carbons (inclusive) is unsubstituted; or 
2) each alkyl of 1-8 carbons (inclusive), alkenyl of 1-8 carbons 
(inclusive) or alkynyl of 1-8 carbons (inclusive) is substituted as 
described in c)2), above; 
e) X is either 
1) an unsubstituted alkylene of 1-3 carbons (inclusive); or 
2) X is an alkylene of 1-3 carbons (inclusive) substituted with one R.sup.2 
group, preferably OR.sup.10, --SR.sup.10, R.sup.15, where R.sup.15 is an 
alkyl of 1-4 carbons (inclusive); phenyl, naphthyl, arylalkyl of 7-14 
carbons (inclusive), preferably benzyl; or 
##STR5## 
f) A.sup.1 and A.sup.2 together are each independently H, H; H, 
--OR.sup.11 ; H, --SR.sup.11 ; H, --N(R.sup.11).sub.2 ; or together 
represent .dbd.S or .dbd.NR.sup.11 ; B.sup.1 and B.sup.2 together 
represent O; and each R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 
and X are as defined in a), b), c), d), and e), above; 
g) A.sup.1 and A.sup.2 together represent O, and B.sup.1 and B.sup.2 
together are each independently H, H; H, --OR.sup.11, H, --SR.sup.11,H, 
--N(R.sup.11).sub.2, or together represent .dbd.S or .dbd.NR.sup.11 ; and 
each R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and X are 
defined in a), b), c), d), and e), above; 
B. Formulae Ia and Ib 
##STR6## 
wherein: a) A.sup.1 and A.sup.2 together represent O, and B.sup.1 and 
B.sup.2 together represent O; 
b) R.sup.1 is H; 
c) R.sup.2 is H, allyl, hydroxyethyl, or alkyl of 1-4 carbons (inclusive), 
preferably methyl; 
d) each R.sup.3, R.sup.4, R.sup.5, and R.sup.6, independently is H, F, Cl, 
Br, I, alkyl of 1-4 carbons (inclusive), preferably methyl, alkoxyl of 1-4 
carbons (inclusive), preferably methoxyl, heteroarylalkenyl, preferably 
pyridylvinyl, heteroarylalkyl, preferably pyridylethyl, cyanoethyl, 
cyanovinyl, aryl of 6-10 carbons, preferably phenyl, alkynyl, arylalkenyl, 
preferably styryl, alkoxycarbonylalkenyl, preferably ethoxycarbonylvinyl, 
or haloalkenyl; 
e) X is either 
1) an unsubstituted alkylene of 1-3 carbons (inclusive), preferably 
--CH.sub.2 --, or --CH.sub.2 CH.sub.2 --; or 
2) X is an alkylene of 1-3 carbons (inclusive) preferably --CH.sub.2 --, or 
--CH.sub.2 CH.sub.2 --, wherein each alkylene of 1-3 carbons (inclusive) 
is substituted with one R.sup.2 group, preferably --OR.sup.11, 
--SR.sup.11, R.sup.15 ; phenyl, naphthyl, aralkyl of 7-11 carbons 
(inclusive), preferably benzyl; or 
##STR7## 
or f) A.sup.1 and A.sup.2 , together are each independently H, H or H, OH 
and B.sup.1 and B.sup.2 together represent O; and each R.sup.1, R.sup.2, 
R.sup.3, R.sup.4, R.sup.5, R.sup.6 and X are as defined in b), c), d), and 
e), above; 
or 
g) A.sup.1 and A.sup.2 together represent O, and B.sup.1 and B.sup.2 
together are each independently H, H or H, OH; and each R.sup.1, R.sup.2, 
R.sup.3, R.sup.4, R.sup.5, R.sup.6 and X are as defined in b), c), d), and 
e), above; 
As used herein with reference to the definition of R.sup.14, the term 
"amino acid" denotes a molecule containing both an amino acid group and a 
carboxyl group. It includes an ".alpha.-amino acid" which has its usual 
meaning as a carboxylic acid which bears an amino functionality on the 
carbon adjacent to the carboxyl group. .alpha.-Amino acids can be 
naturally occurring or non-naturally occurring. Amino acids also include 
"dipeptides" which are defined herein as two amino acids which are joined 
in a peptide linkage. Thus constituents of dipeptides are not limited to 
.alpha.-amino acids, and can be any molecule containing both an amino 
group and a carboxyl group. Preferred are .alpha.-amino acids, dipeptides 
such as lysyl-.beta.-alanine, and aminoalkanoic acids of 2-8 carbons, 
e.g., 3-dimethylaminobutyric acid. 
Preferred embodiments of the fused pyrrolocarbazoles are those represented 
by Formulae I, Ia and Ib in Table I, where the following substitutions are 
made (Roman numerals indicate the Formula representation): 
TABLE I 
__________________________________________________________________________ 
Compound.sup.(1) 
A.sup.1 A.sup.2(2) 
B.sup.1 B.sup.2(3) 
R.sup.2 R.sup.3 
R.sup.4 X 
__________________________________________________________________________ 
I-1 O O H H H CH.sub.2 
I-2 H,H O H H H CH.sub.2 
I-3 O H,H H H H CH.sub.2 
I-4 O O CH.sub.3 
H H CH.sub.2 
1-5.sup.(4) 
-- -- CH.sub.3 
H H CH.sub.2 
I-6 O O H H Br CH.sub.2 
I-7 O O H H F CH.sub.2 
I-8.sup.(5) 
-- -- H H F CH.sub.2 
Ia-1 O O H Cl H CH.sub.2 
Ia-2.sup.(6) 
-- -- H Cl H CH.sub.2 
I-9 H,H O H H Br CH.sub.2 
Ib-1 O O H CH.sub.3 
H CH.sub.2 
I-10 O O H H Cl CH.sub.2 
I-11 O H,H H H Br CH.sub.2 
I-12 H,H O H H F CH.sub.2 
I-13 H,H O H H OCH.sub.3 CH.sub.2 
Ia-3.sup.(7) 
O O H H H CH.sub.2 
Ib-2.sup.(8) 
O O H H H CH.sub.2 
I-14 O O H H H CH.sub.2 CH.sub.2 
I-15 O O H H H CH.dbd.CH 
1-16 O H,H H H H CH.sub.2 CH.sub.2 
I-17 H,H O H H H CH.sub.2 CH.sub.2 
I-18 O H,H H H H CH.sub.2 CH.sub.2 
I-19 H,H O H H H CH.sub.2 CH.sub.2 
I-20 O O H H H S 
I-21 O O H H H O 
I-22 H,H H H H F CH.sub.2 CH.sub.2 
1-23 O H,H H H F CH.sub.2 
I-24 H,H O H H HC.dbd.CHC.sub.6 H.sub.5 
CH.sub.2 
I-25 H,H O H H HC.dbd.CHCO.sub.2 C.sub.2 H.sub.5 
CH.sub.2 
I-26 H,H O CH.sub.2 CH.dbd.CH.sub.2 
H H CH.sub.2 
I-27 H,H O H H C.sub.6 H.sub.5 
CH.sub.2 
I-28 O O H H H CO 
I-29 H,H O CH.sub.2 CH.sub.2 OH 
H H CH.sub.2 
I-30 O H,OH 
H H H CO 
I-31 H,H O H H H CO 
I-32 H,H O H H HC.dbd.CH-2-pyr 
CH.sub.2 
Ia-4.sup.(9) 
O O H H H CH.sub.2 CH.sub.2 
I-33 H,H O H H HC.dbd.CH-4-pyr 
CH.sub.2 
I-34 H,H O H H H.sub.2 CCH.sub.2 -2-pyr 
CH.sub.2 
I-35 H,H O H H HC.dbd.CHCN CH.sub.2 
I-36 H,H O H H C.tbd.CH CH.sub.2 
I-37 O O H H (CH.sub.2).sub.4 CH.sub.3 
CH.sub.2 
Ia-5.sup.(7) 
O O H H H CH.sub.2 CH.sub.2 
Ia-6.sup.(10) 
O O H H H CH.sub.2 CH.sub.2 
Ia-7.sup.(11) 
O O H H H CH.sub.2 CH.sub.2 
I-38 H,OH 
O H H H CH.dbd.CH 
I-39 H,H O H H HC.dbd.CH-2-phthatimide 
CH.sub.2 
1-40 H,H O Iodo CH.sub.2 
I-41 O H,H H H HC.dbd.CH-2-pyr 
CH.sub.2 
I-42 O H,H H H H S 
I-43 H,H O H H H S 
I-44 H,H O H H CH.dbd.CHI CH.sub.2 
__________________________________________________________________________ 
.sup.(1) R.sup.1, R.sup.5, and R.sup.6 are each H except where noted 
.sup.(2) A.sup.1 and A.sup.2 are H,H; H,OH; or both are combined together 
to represent oxygen, where indicated. 
.sup.(3) B.sup.1 and B.sup.2 or both are combined together to represent 
oxygen, where indicated. 
.sup.(4) Compound I5 is a mixture of compounds in a 5/1 molar ratio where 
A.sup.1 A.sup.2 = H,H; B.sup.1 B.sup.2 = O/A.sup.1 A.sup.2 = O; B.sup.1 
B.sup.2 = H,H. 
.sup.(5) Compound I8 is a mixture of compounds in a 2/1 molar ratio where 
A.sup.1 A.sup.2 = H,H; B.sup.1 B.sup.2 = O/A.sup.1 A.sup.2 = O; B.sup.1 
B.sup.2 = H,H. 
.sup.(6) Compound II2 is a mixture of compounds in a 4/1 molar ratio wher 
A.sup.1 A.sup.2 = H,H; B.sup.1 B.sup.2 = O/A.sup.1 A.sup.2 = O; B.sup.1 
B.sup.2 = H,H. 
.sup.(7) R.sup.6 = Br. 
.sup.(8) R.sup.5 = Br. 
.sup.(9) R.sup.6 = F 
.sup.(10) R.sup.6 = 2pyridylvinyl 
.sup.(11) R.sup.6 = 2pyridylethyl 
Particularly preferred compounds of Table I include compounds I-1, I-2, 
I-3, I-4, I-6, I-7, I-9, I-11, I-12, I-14, I-15, I-16, I-17, I-22, I-23, 
I-26, I-29, I-32, I-34, I-39, I-42 and I-43. 
Pharmaceutically acceptable salts of the fused pyrrolocarbazoles also fall 
within the scope of the compounds as disclosed herein. The term 
"pharmaceutically acceptable salts" as used herein means an inorganic acid 
addition salt such as hydrochloride, sulfate, and phosphate, or an organic 
acid addition salt such as acetate, maleate, fumarate, tartrate, and 
citrate. Examples of pharmaceutically acceptable metal salts are alkali 
metal salts such as sodium salt and potassium salt, alkaline earth metal 
salts such as magnesium salt and calcium salt, aluminum salt, and zinc 
salt. Examples of pharmaceutically acceptable ammonium salts are ammonium 
salt and tetramethylammonium salt. Examples of pharmaceutically acceptable 
organic amine addition salts are salts with morpholine and piperidine. 
Examples of pharmaceutically acceptable amino acid addition salts are 
salts with lysine, glycine, and phenylalanine. 
Compounds provided herein can be formulated into pharmaceutical 
compositions by admixture with pharmaceutically acceptable nontoxic 
excipients and carriers. As noted above, such compositions may be prepared 
for use in parenteral administration, particularly in the form of liquid 
solutions or suspensions; or oral administration, particularly in the form 
of tablets or capsules; or intranasally, particularly in the form of 
powders, nasal drops, or aerosols; or dermally, via, for example, 
trans-dermal patches. 
The composition may conveniently be administered in unit dosage form and 
may be prepared by any of the methods well known in the pharmaceutical 
art, for example, as described in Remington's Pharmaceutical Sciences 
(Mack Pub. Co., Easton, Pa., 1980). Formulations for parenteral 
administration may contain as common excipients sterile water or saline, 
polyalkylene glycols such as polyethylene glycol, oils and vegetable 
origin, hydrogenated naphthalenes and the like. In particular, 
biocompatible, biodegradable lactide polymer, lactide/glycolide copolymer, 
or polyoxyethylene-polyoxypropylene copolymers may be useful excipients to 
control the release of the active compounds. Other potentially useful 
parenteral delivery systems for these active compounds include 
ethylene-vinyl acetate copolymer particles, osmotic pumps, implantable 
infusion systems, and liposomes. Formulations for inhalation 
administration contain as excipients, for example, lactose, or may be 
aqueous solutions containing, for example, polyoxyethylene-9-lauryl ether, 
glycocholate and deoxycholate, or oily solutions for administration in the 
form of nasal drops, or as a gel to be applied intranasally. Formulations 
for parenteral administration may also include glycocholate for buccal 
administration, a salicylate for rectal administration, or citric acid for 
vaginal administration. Formulations for trans-dermal patches are 
preferably lipophilic emulsions. 
The materials of this invention can be employed as the sole active agent in 
a pharmaceutical or can be used in combination with other active 
ingredients, e.g., other growth factors which could facilitate neuronal 
survival or axonal regeneration in diseases or disorders. 
The concentrations of the compounds described herein in a therapeutic 
composition will vary depending upon a number of factors, including the 
dosage of the drug to be administered, the chemical characteristics (e.g., 
hydrophobicity) of the compounds employed, and the route of 
administration. In general terms, the compounds of this invention may be 
provided in an aqueous physiological buffer solution containing about 0.1 
to 10% w/v compound for parenteral administration. Typical dose ranges are 
from about 1 .mu.g/kg to about 1 g/kg of body weight per day; a preferred 
dose range is from about 0.01 mg/kg to 100 mg/kg of body weight per day. 
The preferred dosage of drug to be administered is likely to depend on 
such variables as the type and extent of progression of the disease or 
disorder, the overall health status of the particular patient, the 
relative biological efficacy of the compound selected, and formulation of 
the compound excipient, and its route of administration. 
III. Fused Pyrrolocarbazole Utilities 
Our fused pyrrolocarbazoles have evidenced a panapoly of important 
functional activities which find utility in a variety of settings, 
including both research and therapeutic arenas. For ease of presentation, 
and in order not to limit the range of utilities for which these compounds 
can be characterized, we generally describe the activities of the fused 
pyrrolocarbazoles as follows: 
A. Effect on the function and/or survival of trophic factor responsive 
cells 
B. Inhibition of enzymatic activity 
C. Inhibition of inflammation-associated responses 
D. Inhibition of cell growth associated with hyperproliferative states 
Effect on the function and/or survival of trophic factor responsive cells, 
e.g., cells of a neuronal lineage, can be established using any of the 
following assays: (1) cultured spinal cord choline acetyltransferase 
("ChAT") assay; (2) cultured dorsal root ganglion ("DRG") neurite 
extension assay; (3) cultured basal forebrain neuron ("BFN") ChAT activity 
assay. Inhibition of enzymatic activity can be determined using PKC 
inhibition and trk tyrosine kinase inhibition assays. Inhibition of 
inflammation-associated response can be established using an indoleamine 
2,3-dioxygenase ("IDO") mRNA assay. Inhibition of cell growth associated 
with hyperproliferative states can be determined by measuring the growth 
of cell lines of interest, such as an AT2 line in the case of prostate 
cancer. 
As used herein, the term "effect" when used to modify the terms "function" 
and "survival" means a positive or negative alteration or change. An 
effect which is positive can be referred to herein as an "enhancement" or 
"enhancing" and an effect which is negative can be referred to herein as 
"inhibition" or "inhibiting." 
As used herein, the terms "enhance" or "enhancing" when used to modify the 
terms "function" or "survival" means that the presence of a fused 
pyrrolocarbazole has a comparatively greater effect on the function and/or 
survival of a trophic factor responsive cell than a comparative cell not 
presented with the fused pyrrolocarbazole. For example, and not by way of 
limitation, with respect to the survival of, e.g., a cholinergic neuron, 
the fused pyrrolocarbazole would evidence enhancement of survival of a 
cholinergic neuronal population at risk of dying (due to, e.g., injury, a 
disease condition, a degenerative condition or natural progression) when 
compared to a cholinergic neuronal population not presented with such 
fused pyrrolocarbazole, if the treated population has a comparatively 
greater period of functionality than the non-treated population. As a 
further example, and again not by way of limitation, with respect to the 
function of, e.g., a sensory neuron, the fused pyrrolocarbazole would 
evidence enhancement of the function (e.g. neurite extension) of a sensory 
neuronal population when compared to a sensory neuronal population not 
presented with such fused pyrrolocarbazole, if the neurite extension of 
the treated population is comparatively greater than the neurite extension 
of the non-treated population. 
As used herein, "inhibit" and "inhibition" mean that a specified response 
of a designated material (e.g., enzymatic activity) is comparatively 
decreased in the presence of a fused pyrrolocarbazole. 
As used herein the term "neuron," "cell of neuronal lineage" and "neuronal 
cell" includes, but is not limited to, a heterogeneous population of 
neuronal types having singular or multiple transmitters and/or singular or 
multiple functions; preferably, these are cholinergic and sensory neurons. 
As used herein, the phrase "cholinergic neuron" means neurons of the 
Central Nervous System (CNS) and Peripheral Nervous System (PNS) whose 
neurotransmitter is acetylcholine; exemplary are basal forebrain and 
spinal cord neurons. As used herein, the phrase "sensory neuron" includes 
neurons responsive to environmental cues (e.g., temperature, movement) 
from, e.g., skin, muscle and joints; exemplary is a neuron from the DRG. 
As used herein a "trophic factor" is a molecule that directly or indirectly 
affects the survival or function of a trophic factor responsive cell. 
Exemplary trophic factors include Ciliary Neurotrophic Factor (CNTF), 
basic Fibroblast Growth Factor (bFGF), insulin and insulin-like growth 
factors (e.g., IGF-I, IGF-II, IGF-III), interferons, interleukins, 
cytokines, and the neurotrophins, including Nerve Growth Factor (NGF), 
Neurotrophin-3 (NT-3), Neurotrophin-4/5 (NT-4/5) and Brain Derived 
Neurotrophic Factor (BDNF). 
A "trophic factor-responsive cell," as defined herein, is a cell which 
includes a receptor to which a trophic factor can specifically bind; 
examples include neurons (e.g., cholinergic and sensory neurons) and 
non-neuronal cells (e.g., monocytes and neoplastic cells). 
As used herein, "trophic factor activity" and "trophic factor induced 
activity" are defined as any response which directly or indirectly results 
from the binding of a trophic factor (e.g., NGF) to a cell comprising a 
trophic factor receptor (e.g., neuron comprising of a trk). In the case 
of, e.g., NGF binding with trk, an exemplary response would include 
autophosphorylation of trk tyrosine residues leading to increased ChAT 
activity which results in enhanced neuron survival, and/or function. 
As used herein, the term "trk" refers to the family of high affinity 
neurotrophin receptors presently comprising trk A, Irk B and Irk C, and 
other membrane associated proteins to which a neurotrophin can bind. 
As used in the phrases "trophic factor activity" and "trophic 
factor-induced activity," the term "trophic factor" includes both 
endogenous and exogenous trophic factors, where "endogenous" refers to a 
trophic factor already present and "exogenous" refers to a trophic factor 
added to a system. As defined, "trophic factor induced activity" includes 
activity induced by (1) endogenous trophic factors; (2) exogenous trophic 
factors; and (3) a combination of endogenous and exogenous trophic 
factors. 
As used herein the phrase "hyperproliferative state" in reference to the 
term "cells" means cells whose unregulated and/or abnormal growth can lead 
to the development of an unwanted condition, for example, a cancerous 
condition or a psoriatic condition. 
As used herein, "cancer" and "cancerous" refer to any malignant 
proliferation of cells in a mammal. Examples include prostate, benign 
prostate hyperplasia, ovarian, breast and other recognized cancers. As 
used herein the term "psoriasis" and "psoriatic condition" refer to 
disorders involving keratinocyte hyperproliferation, inflammatory cell 
infiltration and cytokine alteration. 
A. Effect on the Function and/or Survival of Trophic Factor Responsive 
Cells 
The disclosed fused pyrrolocarbazoles can be used to enhance the function 
and/or survival of cells of neuronal lineage. In this context, the fused 
pyrrolocarbazoles can be utilized individually or with other fused 
pyrrolocarbazoles, or in combination with other beneficial molecules such 
as indolocarbazoles which also evidence the ability to effect the function 
and/or survival of a designated cell. In situations where the fused 
pyrrolocarbazole is intended to enhance, e.g., neurotrophin activity, 
exogenous neurotrophins may be utilized in conjunction with the fused 
pyrrocarbazole. 
A variety of neurological disorders are characterized by neuronal cells 
which are dying, injured, functionally comprised, undergoing axonal 
degeneration, at risk of dying, etc. These disorders include, but are not 
limited to: Alzheimer's; motor neuron disorders (e.g. amyotrophic lateral 
sclerosis); Parkinson's; cerebrovascular disorders (e.g., stroke, 
ischaemia); Huntingtons; AIDS dementia; epilepsy; multiple sclerosis; 
peripheral neuropathies (e.g., those affecting DRG neurons in 
chemotherapy-associated peripheral neuropathy) including diabetic 
neuropathy; disorders induced by excitatory amino acids; disorders 
associated with concussive or penetrating injuries of the brain or spinal 
cord. 
As set forth in the Examples of this section of the disclosure, the ability 
of a fused pyrrolocarbazole to enhance the function and/or survival of 
cells of a neuronal lineage can be determined by employing any of the 
following assays: 
1. Spinal Cord ChAT Activity Assay 
2. Basal Forebrain ChAT Activity Assay 
3. DRG Neurite Outgrowth Assay 
4. Enhancement of Neurotrophin Activity Assay 
ChAT catalyzes the synthesis of the neurotransmitter acetylcholine and is 
considered an enzymatic marker for a functional cholinergic neuron. A 
functional neuron is also capable of survival. Neuron survival is assayed 
by quantitation of the specific uptake and enzymatic conversion of a dye 
(e.g., calcein AM) by living neurons. Neurotrophins activate the kinase 
activity of a trk, for example, trkA, in cells such as sensory or 
cholinergic neurons. Enhancement of a neurotrophin such as NT-3 can be 
determined by comparing the functional activity of the neurotrophin with 
or without the fused pyrrolocarbazole present. 
Because of their varied utilities, the fused pyrrolocarbazoles disclosed 
herein find utility in a variety of settings. The compounds can be used in 
the development of in vitro models of neuronal cell survival, function, 
identification, or for the screening of other synthetic compounds which 
have activities similar to that of the fused pyrrolocarbazoles. The 
compounds can be utilized in a research environment to investigate, refine 
and determine molecular targets associated with functional responses. For 
example, by radiolabelling a fused pyrrolocarbazole associated with a 
specific cellular function (e.g., mitogenesis), the target entity to which 
the fused pyrrolocarbazole binds can be identified, isolated, and purified 
for characterization. In yet another example, a fused pyrrolocarbazole can 
be used as a screening tool to discover agents which have marginal trophic 
factor-like activity, but when combined with at least one disclosed fused 
pyrrolocarbazole, are capable of enhancing the trophic factor-induced 
activity of a trophic factor-responsive cell. 
Degeneration, death or non-functioning of neurons is a feature of many 
human neurological disorders, including, but not limited to, Alzheimer's; 
motor neuron disorders (e.g., ALS); Parkinson's; cerebrovascular disorders 
(e.g., stroke, ischaemia); Huntingtons; AIDS dementia; epilepsy; multiple 
sclerosis; concussive or penetrating injuries of the brain or spinal cord; 
peripheral neuropathies (e.g., those affecting DRG in 
chemotherapy-associated peripheral neuropathy); and disorders induced by 
excitatory amino acids. Because the disclosed fused pyrrolocarbazoles are 
useful in enhancing trophic factor-induced activities of trophic factor 
responsive cells (e.g., cholinergic and sensory neurons), the disclosed 
compounds beneficially lend themselves to utility as therapeutic agents. 
Thus, because the disclosed compounds have evidenced utility in, e.g., 
enhancement of ChAT activity or DRG neuron survival, the utility of the 
compounds in the treatment of disorders associated with, e.g., decreased 
ChAT activity or the death of DRG neurons, is within the scope of this 
disclosure. 
EXAMPLE III(A)(1) 
Enhancement of Spinal Cord ChAT Activity 
As noted, ChAT is a specific biochemical marker for functional cholinergic 
neurons. Cholinergic neurons represent the major cholinergic input into 
the hippocampal formation, olfactory nucleus, interpeduncular nucleus, 
cortex, amygdala, and parts of the thalamus. In the spinal cord, the motor 
neurons are cholinergic neurons which contain ChAT (Phelps et al., J. 
Comp. Neurol. 273:459-472 (1988)). ChAT activity has been used to study 
the effects of neurotrophins (e.g., NGF or NT-3) on the survival and/or 
function of cholinergic neurons. The ChAT assay also serves as an 
indication of the regulation of ChAT levels within cholinergic neurons. 
Fused pyrrolocarbazoles increased ChAT activity in the dissociated rat 
embryonic spinal cord culture assay (Table II). For example, Compound I-13 
increased ChAT activity 217% over control cultures (not treated with the 
fused pyrrolocarbazole) after allowing a 2-3 hour plating period for cells 
to attach to control tissue culture wells. In these assays, a fused 
pyrrolocarbazole was directly added to a dissociated spinal cord culture. 
Compounds of the invention increased spinal cord ChAT activity in a 
concentration-dependent manner. Compounds which increased ChAT activity at 
least 120% over basal activity were considered active. Increased ChAT 
activity was observed after a single application of a fused 
pyrrolocarbazole. The fused pyrrolocarbazole was added on the same day the 
dissociated spinal cord cell culture was initiated. Increased ChAT 
activity was detectable 48 hours later. 
TABLE II 
______________________________________ 
Effect of Fused Pyrrolocarbazoles on Spinal Cord ChAT Activity 
Compound # % of Control, untreated cultures 
______________________________________ 
I-4 124 
I-5 137 
I-1 148 
I-6 209 
I-7 164 
I-8 200 
I-2 160 
Ia-1 139 
Ia-2 161 
I-9 185 
Ib-1 138 
I-3 174 
I-10 189 
I-11 188 
Ia-3 138 
Ib-2 153 
I-12 173 
I-14 153 
I-13 217 
I-15 182 
I-20 130 
I-16 142 
I-17 197 
I-18 133 
I-22 143 
I-19 203 
I-21 122 
I-24 236 
I-25 168 
I-26 167 
1-23 208 
I-29 154 
I-28 &lt;120 
I-27 120 
I-32 288 
I-30, 31 132 
Ia-4 &lt;120 
I-33 144 
I-34 254 
I-35 121 
I-36 167 
I-37 &lt;120 
Ia-5 132 
Ia-6 139 
Ia-7 &lt;120 
I-38 208 
I-39 268 
I-40 150 
I-41 122 
I-42 177 
I-43 138 
I-44 127 
______________________________________ 
Methods: Fetal rat spinal cord cells were dissociated, and experiments were 
performed as described (Smith et al., J. Cell Biology 101:1608-1621 
(1985); Glicksman et al., J. Neurochem. 61:210-221 (1993)). Dissociated 
cells were prepared from spinal cords dissected from rats (embryonic day 
14-15) by standard trypsin dissociation techniques (Smith et al., J. Cell 
Biology 10:1608-1621 (1985)). Cells were plated at 6.times.10.sup.5 
cells/cm.sup.2 on poly-1-ornithine coated plastic tissue culture wells in 
serum-free N2 medium supplemented with 0.05% bovine serum albumin (BSA) 
(Bottenstein et al., PNAS USA 514-517 (1979)). Cultures were incubated at 
37.degree. C. in a humidified atmosphere of 5% CO.sub.2 /95% air for 48 
hours. ChAT activity was measured after 2 days in vitro using a 
modification of the Fonnum procedure (Fonnum, J. Neurochem. 24:407-409 
(1975)) according to McManaman et al. and Glicksman et al. (McManaman et 
al., Developmental Biology 125:311-320 (1988); Glicksman et al., J. 
Neurochem. 61:210-221 (1993)). 
EXAMPLE III(A)(2) 
Basal Forebrain ChAT Activity Assay 
Fused pyrrolocarbazoles were tested for the ability to increase ChAT 
activity of basal forebrain cultures. Fused pyrrolocarbazoles were found 
to increase ChAT activity in basal forebrain cultures (Table III; 
"N.T."="not tested"). Control cultures did not receive a fused 
pyrrolocarbazole. 
TABLE III 
______________________________________ 
Fused Pyrrolocarbazoles Promote 
ChAT Activity in Basal Forebrain 
ChAT Activity (% of Control) 
Compound 100 nM 250 nM 500 nM 1000 nM 
______________________________________ 
I-1 inactive inactive inactive 
NT 
I-2 inactive 137 137 inactive 
I-3 inactive inactive 130 NT 
I-12 279 389 NT NT 
I-24 inactive 151 NT NT 
I-36 122 131 123 inactive 
I-29 140 189 194 210 
I-34 inactive 192 inactive 
inactive 
______________________________________ 
Methods: The basal forebrain was dissected from rat embryos (day 17 or 18 
embryos) and the cells were dissociated with a neutral protease 
(Dispase.TM., Collaborative Research). Neurons were plated at a density of 
5.times.10.sup.4 cells/well (1.5.times.10.sup.5 cells/cm.sup.2) in 
poly-1-ornithine and laminin coated plates. Cells were cultured in 
serum-free N2 medium containing 0.05% BSA at 37.degree. C. in a humidified 
atmosphere, 5% CO.sub.2 /95% air. ChAT activity was assessed 5 days after 
plating by using the ChAT assay as described in Example III(A)(1). 
EXAMPLE III(A)(3) 
DRG Neurite Outgrowth Assay 
Fused pyrrolocarbazoles promoted nerve fiber (i.e., neurite) outgrowth in 
explant (i.e., primary) cultures of chick dorsal root ganglion neurons. 
Dorsal root ganglion (i.e., DRG) nerve fiber outgrowth was increased when 
a fused pyrrolocarbazole was added to cultures at a concentration of 200 
nM (Table IV). Control cultures consisted of: 1) no added NGF or fused 
pyrrolocarbazole ("Control"), or 2) 50 ng/ml NGF, a neurotrophin known to 
promote neurite extension in DRG cultures ("NGF"). 
TABLE IV 
______________________________________ 
Fused Pyrrolocarbazoles Promote DRG Neurite Outgrowth 
Compound 
Concentration 200 nM 
______________________________________ 
Control few sparse neurites visible 
NGF dense outgrowth of neurites that reaches the edges of 
the well 
I-1 modest number of neurites 
I-2 modest to dense outgrowth of neurites 
I-3 dense outgrowth of neurites but not quite reaching 
the edges of the well 
______________________________________ 
Methods: Dorsal root ganglia were dissected from chick embryos (embryonic 
day 9) and individual ganglia were plated on poly-1-ornithine and laminin 
coated plates. A fused pyrrolocarbazole or 50ng/ml NGF was each added to 
independent cultures alter allowing a 1-2 hour cell attachment period. 
Explants were cultured for 48 hours in serum-free N2 medium supplemented 
with 0.05% BSA (Bottenstein et al., PNAS USA 76:514-517 (1979)). Cultures 
were maintained at 37.degree. C. in a humidified atmosphere, 5% CO.sub.2 
/95% air. Nerve fiber outgrowth was assessed by the density and length of 
neurites. It should be apparent to those skilled in the art that neurite 
extension assays are semi-quantitative and involve a visual comparison 
between control and experimental neuronal cell cultures (Alberts et al., 
Molecular Biology of the Cell, 2ed. Garland Publishing, Inc., New York 
(1989). 
EXAMPLE III(A)(4) 
Enhancement of Neurotrophin Activity Assay 
Fused pyrrolocarbazoles were tested for the ability to enhance the activity 
of the neurotrophin NT-3 in basal forebrain cultures. ChAT activity was 
assayed as a measure of cholinergic neuron function and survival. The 
concentration of NT-3 (100 ng/ml) used in these experiments increased ChAT 
activity over control cultures (untreated with NT-3 or a fused 
pyrrolocarbazole) by 140%. Compounds I-1, I-6, I-7, and Ia-1 each enhanced 
ChAT activity in the presence of a 100 ng/ml concentration of NT-3. When 
these compounds were each added alone to basal forebrain neurons in the 
absence of NT-3, there was no effect on ChAT activity. The increase in 
ChAT activity was greater than that elicited by NT-3 alone, as indicated 
in the bar-graph presented in FIG. 1. 
Methods. Basal forebrain cultures were prepared from embryonic rats 
(embryonic day 17) and dissociated with the neutral protease Dispase.TM.. 
Cells were plated at a density of 4.times.10.sup.5 cells/cm.sup.2 on 
poly-1-ornithine coated plastic tissue culture plates in a mixture of DMEM 
and F12 media (50/50 v/v GIBCO) supplemented with 5% horse serum and 0.5% 
fetal bovine serum. Cells were incubated at 37.degree. C. in a humidified 
atmosphere of 5% CO.sub.2 /95% air for 5 days. ChAT activity was measured 
as described in Example III(A)(1). 
Recombinant rat NT-3 was produced by using a recombinant baculovirus 
expression vector under the control of the polyhedron virus promoter 
(Fraser, In Vitro Cell. and Dev. Biol. 25:225-235 (1989)). The plasmid 
pXM-NT3 (Hallbook et al., Neuron 6:845-858 (1991), which contained the rat 
NT-3 cDNA clone, was provided by Dr. Ira Black (University of Medicine and 
Dentistry of New Jersey, Piscataway, N.J.). NT-3 cDNA was subcloned into 
the transfer vector pVL1392 (In Vitrogen Corp., San Diego, Calif.) for 
recombinant virus production. Recombinant baculovirus was produced as 
described in Meyer et al. (Meyer at al., J. Neurochem 62:825-833 (1994)). 
EXAMPLE HI(A)(5) 
DRG Neuron Survival Assay 
Fused pyrrolocarbazoles promoted dorsal root ganglion (DRG) neuronal 
survival in cultures of chick DRG neurons. Cell survival was measured by 
uptake of calcein AM, an analog of the viable dye, fluorescein diacetate. 
Calcein is taken up by viable cells and cleaved intracellularly to 
fluorescent salts which are retained by intact membranes of viable cells. 
Microscopic counts of viable neurons correlate directly with relative 
fluorscence values obtained with the fluorimetric viability assay. This 
method thus provides a reliable and quantitive measurement of cell 
survival in the total cell population of a given culture (Bozyczko-Coyne 
et al., J. Neur. Meth. 50:205-216, 1993). 
Dorsal root ganglion neuronal survival was enhanced by fused 
pyrrolocarbazoles with activity being observed at 100-500nM (Table V). All 
of these analogs were also active in increasing spinal cord ChAT activity 
(See Example III(A)(1), Table II). Microscopic examination of the dorsal 
root ganglion neurons stimulated with the six active compounds indicated 
enhanced nerve fiber outgrowth as well. 
TABLE V 
______________________________________ 
Fused Pyrrolocarbazoles Promote Survival of DRG Neurons 
Neuronal Survival (% of Control) 
Compound 100 nM 250 nM 500 nM 
______________________________________ 
I-12 126 165 178 
I-34 159 203 207 
I-24 154 167 163 
I-15 inactive 132 inactive 
I-32 173 164 151 
I-23 inactive 128 135 
______________________________________ 
Methods: Dorsal root ganglia were dissected from embryonic age day 9 chick 
embryos and dissociated cells prepared by subsequent Dispase (neutral 
protease, Collaborative Research) dissociation. Neurons were seeded at low 
density (3.times.10.sup.4 cells/cm.sup.2) into 96 well poly-L-ornithine 
and laminin coated plates. Cells were cultured for 48 hours in serum-free 
N2 medium (Bottenstein and Sato, 1979) at 37.degree. C. in a humidified 
atmosphere, 5% Co.sub.2 /95% air. Cell survival was assessed at 48 hours 
using the viable fluorimetric assay described above. 
B. Inhibition of Enzymatic Activity 
The ability of the indolocarbazole K-252a, for example, to inhibit the 
enzymatic activity of protein kinase ("PKC") is well known and documented. 
Inhibition of PKC activity has been suggested as an approach for 
inhibiting, mediating, reducing and/or preventing a variety of disease 
states, including inflammatory diseases, allergy and cancerous conditions, 
as indicated in the following representative references: U.S. Pat. Nos. 
4,877,776, and 4,923,986; European Patent Application 558,962 (published 
Sep. 8, 1993 in the name of E. R. Squibb & Sons, Inc.); Tadka, T. et al., 
170(3) Biochem. Biophys. Res. Comm. 1151, 1980). The tyrosine kinases, of 
which trk is a member, are enzymes which catalyze the transfer of the 
T-phosphate of ATP to the hydroxyl group of tyrosine on many key proteins. 
Activated protein tyrosine kinases have been identified as the products of 
approximately half of known oncogenes (see Chang, C-J & Geahlen, R. L. 
55(11) J. Nat. Prods. 1529, 1992). Inhibiting, mediating, reducing and/or 
preventing a variety of cancerous conditions via inhibition of protein 
kinases has been set forth (see Chang, C-J, supra). 
Because of the important association between protein kinase activity and 
certain diseases and disorders, our fused pyrrolocarbazoles also find 
utility in both research and therapeutic settings. For example, in a 
research environment, the compounds can be used in the development of 
assays and models for further enhancement of the understanding of the 
roles that inhibition of protein kinase (e.g., PKC, trk tyrosine kinase) 
play in the mechanistic aspects of the associated disorders and diseases. 
In a therapeutic setting, the compounds which inhibit these enzymatic 
activities can be used to inhibit the deleterious consequences of these 
enzymes with respect to disorders such as cancer. 
As we demonstrate in the Examples of this section, inhibition of enzymatic 
activity using our fused pyrrolocarbazoles can be determined using the 
following assays: 
1. PKC Activity Inhibition Assay 
2. trkA Tyrosine Kinase Activity Inhibition Assay 
EXAMPLE III(B)(1) 
PKC Activity Inhibition Assay 
Fused pyrrolocarbazoles inhibited the activity of protein kinase C (Table 
VI). The protein kinase C assay has been disclosed (Murakata et al., U.S. 
Pat. No. 4,923,986; Kikkawa et al., J. Biol. Chem. 257:13341-13348 
(1982)). The assay was performed with several concentrations of fused 
pyrrolocarbazoles. The concentration at which protein kinase C was 50% 
inhibited (IC.sub.50) was determined. 
TABLE VI 
______________________________________ 
Protein Kinase C Inhibition 
COMPOUND PKC INHIBITION IC.sub.50 (.mu.M) 
______________________________________ 
I-1 0.07 
I-6 1.0 
I-7 0.15 
I-2 0.11 
I-9 4.5 
I-3 0.1 
I-11 0.45 
I-12 0.085 
I-14 0.015 
I-15 0.05 
I-20 0.15 
I-16 0.035 
I-17 1.0 
I-22 0.25 
I-24 8.0 
I-26 0.3 
I-23 0.06 
I-29 0.04 
______________________________________ 
EXAMPLE III(B)(2) 
trkA Tyrosine Kinase Activity Inhibition Assay 
Fused pyrrolocarbazoles inhibited trkA tyrosine kinase activity as 
determined by ELISA. trkA is a high affinity receptor for neurotrophins. 
Fused pyrrolocarbazoles were added to 96-well microtiter plates that were 
previously coated with a phosphorylation substrate (phospholipase 
C-.gamma. (PLC.gamma.)/pGEX fusion protein) (see Rotin, et al., 11 EMBO J. 
559, 1992). These compounds were then tested for the ability to inhibit 
substrate phosphorylation by the trkA tyrosine kinase. Fused 
pyrrolocarbazoles inhibited trkA tyrosine kinase activity with IC.sub.50 
's of approximately 20 nM (Table VII). 
TABLE VII 
______________________________________ 
Inhibition of trkA Tyrosine Kinase Activity 
COMPOUND INHIBITION OF trkA KINASE IC.sub.50 (nM) 
______________________________________ 
I-2 20.6 
I-3 24.5 
I-12 26.7 
I-1 &gt;1,000 
I-7 &gt;1,000 
I-15 &gt;1,000 
I-17 66.0 
I-24 &gt;1,000 
I-23 70.6 
I-29 18.4 
I-32 &gt;1,000 
I-30, I-31 &gt;1,000 
______________________________________ 
Methods: 96-well ELISA plates (Nunc) were coated with 100 .mu.l/well of the 
phosphorylation substrate (40 .mu.g/ml) PLC.gamma./pGEX fusion protein) in 
20 mM Tris, pH 7.6, 137 mM NaCl, and 0.02% NaN.sub.3 overnight at 
4.degree. C. Plates were then washed three times with TBST (20 mM Tris, pH 
7.6, 137 mM NaCl, 0.2% Tween-20) and subsequently blocked with 3% bovine 
serum albumin (BSA) in TBST for 1 hour at 37.degree. C. Plates were washed 
three times with TBST, followed by two washes with TBS (TBST sans 
Tween-20). Fused pyrrolocarbazoles were then added at various 
concentrations to a reaction mixture (50 mM HEPES, pH 7.4, 5 mM 
MnCl.sub.2, 5 mM MgCl.sub.2, 140 mM NaCl, 16 .mu.M ATP, and 15 ng trkA in 
a total volume of 100.mu.L.). As a negative control, 100 mM EDTA was 
included in the reaction solution. The plates were then incubated at 
37.degree. C. for 15 min. The detection antibody, monoclonal 
anti-phosphotyrosine antibody (UBI), was added at a dilution of 1:2000 in 
TBST, and incubated for 1 hour at 37.degree. C. Plates were then washed 
three times with TBST, followed by a 1 hour incubation at 37.degree. C. 
with alkaline phosphatase-labeled goat anti-mouse IgG (1:2000 in TBST 
(Bio-Rad)). After washing three times with TBST followed by two washes 
with TBS, a colored product was produced by using NADPH as substrate for 
alkaline phosphatase, and the coupled reactions of diaphorase and alcohol 
dehydrogenase (GIBCO-BRL ELISA amplification system). The colored product 
was read at 490 nm in a microplate reader (Biotek). 
C. Inhibition of Induction of a Response Associated with Inflammation 
The human interferons (IFNs) designated alpha (IFN.alpha.), beta 
(IFN.beta.) and gamma (IFN.gamma.) induce their biological responses in 
cells from two different cell surface receptors, a first receptor for 
IFN.alpha. and IFN.beta. and a second receptor for IFN.gamma.. 
Transcription of IFN specific genes is necessary for the subsequent 
IFN-induced biological responses. The IFN receptors have no known kinase 
activity, but the binding of the specific IFN with its receptor stimulates 
the phosphorylation of intracellular proteins; when these proteins are 
phosphorylated, they rapidly translocate to the nucleus and initiate 
transcription of IFN-specific genes. 
Many IFN-induced biological responses, i.e., the inhibition of viral 
replication, inhibition of tumor growth, etc., are beneficial to the 
animal. However, a number of the IFN.gamma. biological responses are 
deleterious. For example, when given exogenously, IFN.gamma. exacerbates 
the symptoms of multiple sclerosis and rheumatoid arthritis; endogenous 
IFN.gamma. is also believed to play a role in exacerbating the symptoms of 
these diseases. Furthermore, IFN.gamma. is also believed to play a 
prominent role (causative and negative) in sepsis and general 
inflammation. 
Indoleamine 2,3-dioxygenase (IDO) is an enzyme which initiates tryptophan 
degradation in the kynuerinine pathway in macrophages, monocytes and 
astrocytes. The tryptophan degradation pathway, as well as the interferon 
system, are relatively inactive in cells under normal, physiological 
conditions. Quinolinic acid, normally present in very low, non-deleterious 
amounts, is derived from the degradation of tryptophan. Quinolinic acid 
has been proposed to be neurotoxic by overstimulating glutamate (NMDA) 
receptors, resulting in the influx of Ca.sup.++ and subsequent death of 
NMDA receptor-positve neurons. It has been proposed that a number of 
inflammatory brain diseases are caused by an excess of quinolinic acid. 
Under pathological situations, increased IFN.gamma. in response to such 
situations may activate the tryptophan degradation pathway, thus 
increasing levels of quinolinic acids, resulting in the death of neurons 
(see Heyes, M. P. et al. 115 Brain 1249, 1992). Elevated levels of 
quinolinic acid have been reported in a variety of inflammatory brain 
disorders including HIV, Lyme disease, head trauma, stroke, autoimmune 
diseases and sepsis (see 259 Science 25, 1993). 
K-252a and staurosporine both inhibit the transcription of IFN.alpha. genes 
and this inhibition of transcription is not associated with the inhibition 
of protein kinase C. This was evidenced by prolonged treatment of cells 
with TPA which eliminated all detectable PKC by immunoblot analysis, but 
not IFN.alpha. induced transcription and the inhibition thereof by K-252a 
and staurosporine (see Kessler and Levy 266 IBC 23471, 1991; see also 
Schindler et al 257 Science 809, 1994). K-252a has also been suggested as 
having antiflammatory and antiallergic effects in vivo (see Ohimori, K. et 
al 38(1), 6 Drug Res 809, 1988). 
Given the deleterious association between IDO and quinolinic acid, and the 
implications of quinolinic acid with a number a pathological conditions, 
agents which are capable of inhibiting the induction of IDO by IFN.gamma. 
are useful in a research environment where the compounds which inhibit 
induction of IDO can be radiolabelled in order to determine their 
identity, isolate and purity cells to which these compounds bind and which 
are involved in the inflammation cascade. In a therapeutic setting, the 
compounds which inhibit such induction can be used to inhibit, mediate, 
prevent and or treat diseases and disorders such as sepsis, multiple 
sclerosis, rheumatoid arthritis and chronic inflammation diseases. 
EXAMPLE III(C)(1) 
Inhibition of Induction By IFN.gamma. of IDO mRNA 
Fused pyrrolocarbazoles in accordance with our invention were tested for 
their ability to inhibit the induction by IFN.gamma. of indoleamine 
2,3-dioxygenase (IDO) mRNA in THP-1 cells, a human monocyte cell line. 
Cell Culture: THP-1 cells (American Type Culture Collection, Rockville, 
Md.), a human monocytic leukemia cell line, were grown in RPMI 1640 medium 
(Mediatech, Herndon Valley, Va.) with 50 .mu.M 2-mercaptoethanol and 10% 
fetal bovine serum. Cells were plated in T75 culture flasks, at 
4.times.10.sup.4 cells/cm.sup.2 in 10 ml of medium, and were immediately 
treated with fused pyrrolocarbazoles at various concentrations. After 30 
minutes recombinant (E. coli) IFN.gamma. (Boehringer Mannheim Corporation, 
Indianapolis, Ind.) was added at 200-400 units/mi. Cells were incubated 
(37.degree. C., 5% CO.sub.2 /95% Air) for 48 hours after treatment. 
RNA Isolation: Cells were pelleted by centrifugation (50 x g, 7 min.) and 
medium was decanted. The cells were then washed two times with phosphate 
buffered saline pH 7.2 (PBS) (Mediatech, Herndon Valley, Va.). The washed 
cell pellet was lysed in 2 ml RNAzol B (Tel-Test, Inc., Friendswood, 
Tex.). RNA was isolated by chloroform extraction, precipitated, and washed 
following the "RNAzol B isolation of RNA" protocol accompanying this 
product. RNA was then solubilized in H.sub.2 O, and the concentration and 
purity were determined by reading the absorbance at A.sub.260 nm and 
A.sub.280 nm. Finally, the RNA was reprecipitated in ethanol, overnight at 
-20.degree. C. 
cDNA Probes: Indoleamine 2,3-dioxygenase (IDO).sup.. cDNA was received from 
Sohan L. Gupta, Ph.D. (Hippie Cancer Research Center, Dayton, Ohio) (see 
Da., W. & Gupta, S. L. 168 Biochem. Biophys. Res. Commun. 1, 1990 and 
Hassanain, H. H. et al. 268 J. Biol. Chem. 5077, 1993). 
Glyceraldehyde-3-phosphate dehydrogenase (GAPD) cDNA was obtained through 
American Type Culture Collection (Rockville, Md.). These cDNA's were 
produced and purified using standard methods (see, Sambrook, Fritsch, 
Maniatis (1989) Molecular Cloning a Laboratory Manual/Second Edition 1, 
1.21-1.24, 1.74-1.81, hereinafter in this Example, "Maniatis a") using 
Qiagen plasmid purification kits (Qiagen Inc., Chatsworth, Calif.). DNA 
concentration and purity were determined by absorbance at 280 nm and 260 
nm. Specific DNA inserts were cut out by standard methods using 
restriction enzymes, and subsequently separated on agarose gels as in 
Maniatis (see, Sambrook, Fritsch, Maniatis (1989) Molecular Cloning a 
Laboratory Manual/Second Edition 1, 6.9-6.15, hereinafter in this Example, 
"Maniatis b"). cDNA probes were further purified for [.sup.32 p] labeling 
using the Geneclean II DNA purification kit (BIO 101, Inc., La Jolla, 
Calif.). Probes were labeled with dCTP-.alpha.-.sup.32 P (Amersham Corp., 
Arlington Heights, Ill.) by random primer labeling, using the Prime-a-Gene 
Labeling System (Promega Corp., Madison, Wis.). 
Analysis and quantification of mRNA: IDO mRNA was detected by Northern blot 
analysis (see Maniatis a, p. 7.39-7.51) using standard methods. After 
separation by electrophoresis on 1% agarose gels containing formaldehyde, 
the RNA was transferred to a Magnagraph nylon transfer membrane (Micron 
Separations Inc., Westboro, Mass.). The blots were then hybridized with 
[.sup.32 P]-labeled IDO cDNA (Hipple Cancer Research Center, Dayton, Ohio) 
according to standard methods (see Maniatis a, p. 7.52), washed and placed 
in phosphorimaging cassettes for 1 to 4 days. Quantification of IDO mRNA 
was carried out using a phosphorimager (Molecular Dynamics) in which 
density (i.e., amount of RNA) is expressed as relative phosphorimager 
units. The blots were subsequently probed for glyceraldehyde-3-phosphate 
dehydrogenase (GAPD) mRNA (ATCC, Rockville, Md.), an mRNA that does not 
change with IFN.gamma. treatment. GAPD mRNA measurement by phosphorimager 
quantification of Northern blots serves as a means to normalize for 
potential sample to sample differences in the amount of total RNA loaded 
on gels. The resulting ratio of IDO mRNA/GAPD mRNA is expressed in Table 
VIII as a percentage of the ratio observed in IFN.gamma.-induced cells 
(defined as 100%). 
TABLE VIII 
______________________________________ 
Addition to cells Phosphorimager units 
Compound (nM) 
IFN.gamma. (units/ml) 
% of IFN.gamma.-treated cells 
______________________________________ 
No Compound 
(200) 100 
Added 
No Compound 
(0) 0.75 
Added 
I-29 (200 nM) 
(200) 57 
I-2 (400 nM) 
(400) 55 
I-9 (400 nM) 
(400) 60 
I-11 (400 nM) 
(400) 49 
I-32 (400 nM) 
(400) 70 
______________________________________ 
D. Inhibition of Cell Growth Associated with Hyperproliferative States 
Although nerve growth factor (NGF) is a neurotrophic protein which plays a 
crucial role in the development and maintenance of sensory and sympathetic 
neurons, there is increasing evidence that NGF, in addition to actions 
within the nervous system, possesses a number of biological effects on 
cells of the immune-inflammatory compartment. Keratinocytes, the most 
numerous cells in the epidermis, are thought to be crucial to cutaneous 
inflammatory responses (Barker, J. N. W. N. et al. 337 Lancet 211, 1991); 
psoriasis, a disorder characterized by keratinocyte hyperproliferation, 
inflammatory cell infiltration, and alteration of certain cytokines 
(Jablonaka, S. et al. In: Roencgk, H. H., Miaback H. (eds.) Psoriasis 
Dekker, Inc., New York, N.Y. 1991, pp. 261-342). NGF is also reported to 
activate most cells and T-lymphocytes, which invade the psoriatic lesion; 
interleukin-6, also expressed in high levels in psoriatic skin and which 
also stimulates proliferation of human keratinocytes, can enhance NGF 
secretion (see Grossman, R. M. et 1.5 al. 86 PNAS 6367, 1989 and Frei, K 
et al. 19 Eur. J. Immunol. 689, 1989). Recently, it was reported that NGF 
stimulates the proliferation of human keratinocytes in culture, and that 
K-252a prevents such proliferation (see Pincelli, C. et al., 103(1) J. 
Invest. Derma. 13, 1994). 
Use of our fused pyrrolocarbazoles can be beneficially exploited in the 
arena of psoriatic conditions, given the ability of K-252a to inhibit the 
proliferation of human keratinocytes and the link between the 
hyperproliferation of keratinocytes and psoriasis; the fused 
pyrrolocarbazoles can be utilized to further enhance the understanding of 
inhibition of keratinocytes and the cellular relationship between, e.g., 
NGF, keratinocytes and disorders exemplified by psoriasis. In therapeutic 
settings, the fused pyrrolocarbazoles can be advantageously utilized to 
inhibit the hyperproliferation of keratinocytes, thus acting to inhibit, 
mediate, reverse and/or prevent the occurrence of a psoriatic condition. 
Cancers, almost universally by definition, involve hyperproliferative 
growth of cells to a malignant state, typically resulting in the formation 
of tumors. Thus, we have investigated the ability of our compounds to 
effect the growth of prostate cancer cells as an exemplary approach to 
defining compounds which inhibit the growth of cells associated with a 
hyperproliferative state. Accordingly, our compounds can also be utilized 
in this context for both research and therapeutic avenues: in a research 
environment, the compounds can be used to, e.g., screen for other 
compounds that can also inhibit the growth of cells associated with 
hyperproliferative states; in a therapeutic arena, the compounds which 
beneficially inhibit the growth of specific cells associated with specific 
diseases and/or disorders can be advantageously exploited in the 
mediation, treatment and/or prevention of such diseases or disorders. 
EXAMPLE III(D)(1) 
Inhibition of Growth of Prostate Cancer Cell Line Using Fused 
Pyrrolocarbazoles 
AT-2 cells are a prostate cancer cell sub-line derived from the Dunning H 
tumor, graciously provided to us by Dr. John Isaacs (John Hopkins, M.D.). 
Unlike the Dunning H tumor cells, AT-2 cells can be grown in vitro. 
Methods: AT-2 cells (7.5.times.10.sup.4 cells/well) were plated on tissue 
culture plastic in 96-well plates in the presence of RPMI-1640 medium 
containing 10% fetal calf serum, 250 nM dexamethasone, 2 mM glutamine, 1 
mM sodium pyruvate, and penicillin/streptomycin antibiotics. The next day, 
compounds were added at 4 concentrations (10, 1, 0.1, 0.01 .mu.M) to 
determine the approximate IC.sub.50 range. Cultures were assayed 3 days 
later for cell number using the MTS 
[(3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl 
)-2H-tetrazolium, inner salt)] assay. The MTS assay (purchased as a kit 
from Promega) measures the formation of an aqueous soluble formazan 
(detected by a plate reader at 490nm) produced by the bioreduction of a 
tetrazolium compound (MTS) in metabolically active cells via mitochondrial 
succinate dehydrogenase. After determining linearity of the substrate 
incubation time over a range of cell plating densities, the amount of 
product measured is directly proportional to cell number. MTS (333 ug/ml) 
and 25 .mu.M phenazine methosulfate are mixed and added directly to the 
culture medium, and incubated at 37.degree. C. in the 5% CO.sub.2 /95% air 
incubator for 0.5-4 h. Absorbance of the product at 490nm is read on the 
BIO-TEK plate reader. Background values were obtained from wells 
containing culture medium with substrate solution, but no cells. In 
addition, values were also obtained from wells containing cells plated at 
day 0 and assayed on the day compound was added (day 1) in order to 
determine the number of cells at the time compound was added. After the 
initial dose-finding experiment was completed, subsequent experiments were 
set up so that there were 3 or more concentrations near the predicted 
IC.sub.50. 
TABLE IX 
______________________________________ 
Compound # AT-2 cell growth IC.sub.50 (nM) 
______________________________________ 
I-3 380 
I-7 1370 
I-29 3260 
I-2 4600 
I-24 &gt;10,000 
I-14 3070 
I-15 4300 
I-20 &gt;10,000 
I-21 &gt;10,000 
______________________________________ 
IV. Synthetic Processes for Production of Fused Pyrrolocarbazoles 
The invention discloses a method for preparing a D-ring-fused 
pyrrolocarbazole, the method comprising the steps of: 
a) obtaining an indole represented by general formula IV, wherein R.sup.2 
is H, SO.sub.2 R.sup.9, CO.sub.2 R.sup.9, or alkyl of 1-4 carbons, and 
each R.sup.3a and R.sup.4a is H, F, Cl, Br, I, --OR.sup.9, 
--O(CH.sub.2).sub.n NR.sup.7 R.sup.8, NR.sup.7 R.sup.8, --SR.sup.11, 
alkyl, aryl, heteroaryl, --(CH.sub.2).sub.n SR.sup.11, --(CH.sub.2).sub.n 
OR.sup.9, or --(CH.sub.2).sub.n NR.sup.7 R.sup.8 ; 
b) reacting said indole with a 2-indanone represented by the following 
general Formula: 
##STR8## 
wherein each R.sup.5a and R.sup.6a is H, F, Cl, Br, I, alkyl, aryl, 
heteroaryl, CN, NO.sub.2, OR.sup.9, --O(CH.sub.2).sub.n NR.sup.7 R.sup.8, 
CO.sub.2 R.sup.9, SO.sub.2 R.sup.9, SR.sup.11, --(CH.sub.2).sub.n 
S(O).sub.y R.sup.9, --(CH.sub.2).sub.n SR.sup.11, NR.sup.7 R.sup.8, or 
--(CH.sub.2).sub.n NR.sup.7 R.sup.8, and X is an alkylene group of 1-3 
carbons (inclusive) or --C(R.sup.10).sub.2 --, under conditions capable of 
forming a 2-(2-cycloalkenyl)indolo tertiary alcohol (Formula V) and 
eliminating the hydroxyl group of said alcohol to form the corresponding 
2-(2-cycloalkenyl)indole (Formula VI); 
c) reacting said 2-(2-cycloalkenyl)indole with an imide represented by the 
following general Formula: 
##STR9## 
wherein R.sup.1 is defined above, under conditions which form a 
tetrahydropyrrolocarbazole represented by general Formula VII; 
and 
d) dehydrogenating the tetrahydrocarbazole ring of said 
tetrahydropyrrolocarbazole under conditions which form a fused 
pyrrolocarbazole of general Formula VIII. 
The invention discloses a method for making substantially pure 
regiospecific D-ring-fused pyrrolocarbazole lactam isomers, said method 
comprising the steps of: 
a) obtaining a fused pyrrolocarbazole represented by general formula VIII, 
wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.4a, R.sup.5a, R.sup.6a and X are 
as previously defined; 
b) reducing the imide group of said fused pyrrolocarbazole under conditions 
which form two fused pyrrolocarbazole lactam isomers represented by 
general Formulae IX and X; 
and 
c) separating said isomers under conditions which produce substantially 
pure regiospecific D-ring-fused pyrrolocarbazole lactam isomers. 
The invention discloses a method of making a regiospecific D-ring fused 
pyrrolocarbazole lactam isomer, said method comprising the steps of: 
a) obtaining a compound of the general Formula XI, wherein R.sup.2, 
R.sup.3a, R.sup.4a, R.sup.5a, R.sup.6A are as previously defined, and X is 
S, O, CO, alkylene or 1-3 carbons, --C(R.sup.10).sub.2, --CH.sub.2 Z--, 
--ZCH.sub.2 --, or --CH.sub.2 ZCH.sub.2 --; 
b) reacting said compound with a lower alkyl .beta.-cyanoacrylate, 
preferably ethyl .beta.-cyanoacrylate, under conditions which form 
tetrahydrocarbazole cyano-ester isomers represented by general Formulae 
XII and XV, wherein R is a lower alkyl group; 
c) separating said isomers under conditions which produce substantially 
pure regiospecific tetrahydrocarbazole cyano-ester isomers; 
d) separately dehydrogenating the tetrahydrocarbazole ring of each of said 
isomers sufficient to form the corresponding carbazole cyano-esters 
(Formulae XIII and XVI); and 
e) separately reacting each of said carbazole cyano-esters under reductive 
conditions which independently produce regiospecific fused 
pyrrolocarbazoles represented by general formulae XIV and XVII. 
The invention discloses a method of making a D-ring-fused pyrrolocarbazole, 
said method comprising the steps of: 
a) obtaining an indole represented by general formula IV, wherein R.sup.2, 
R.sup.3a and R.sup.4a are as previously defined; 
b) reacting said indole with a 2-benzocycloalkanone represented by the 
following general formula: 
##STR10## 
wherein R.sup.5a and R.sup.6a are as previously defined and X is an 
alkylene group of 2-3 carbons (inclusive); said reacting being under 
conditions which form a 2-(2-(1,2,3,4-tetrahydroarylalkyl)) indolyl 
tertiary alcohol; and eliminating the hydroxyl group of said alcohol to 
form the corresponding 2-(2-cycloalkenyl)indole; 
c) reacting said 2-(2-cycloalkenyl)indole with an imide represented by the 
following general Formula: 
##STR11## 
where R.sup.1 is as defined above; said reacting being under conditions 
which form a tetrahydroarylalkylpyrrolocarbazole represented by the 
general Formula XVIII; 
and either 
i) dehydrogenating the D-ring of said pyrrolocarbazole under conditions 
which produce the corresponding fused pyrrolocarbazole represented by 
general Formula XIX; 
or 
ii) dehydrogenating the E-ring of said pyrrolocarbazole under conditions 
which produce the corresponding fused pyrrolocarbazole represented by 
general Formula XX. 
The invention discloses a method of making a D-ring-fused pyrrolocarbazole, 
said method comprising the steps of: 
a) obtaining a lower alkyl stannylindole represented by general formula 
XXI, wherein R.sup.2 is --CO.sub.2 H, --SO.sub.2 R.sup.9, --CO.sub.2 
R.sup.9 or alkyl; R.sup.3a and R.sup.4 are as defined above; 
b) coupling said lower alkyl stannylindole with a compound represented by 
the following general Formula: 
##STR12## 
wherein R.sup.5a and R.sup.6a are as defined above; X is S, O, CO, alkylene 
of 1-3 carbons, --C(R.sup.10).sub.2 --, --CH.sub.2 Z--, --ZCH.sub.2 -- and 
CH.sub.2 ZCH.sub.2 --; and Y is Br, I or --OSO.sub.2 CF.sub.3, said 
coupling being under conditions which form an indole of general formula 
XXII; 
c) separately reacting said indole with either: 
i) an imide represented by the following general formula: 
##STR13## 
or ii) a lower alkyl .beta.-cyanoacrylate; 
each under conditions which independently form the corresponding 
indolo-imide represented by general Formula XXIII; 
and 
d) cyclizing said indoloimide under conditions which form a fused 
pyrrolocarbazole represented by the following general Formula XXIV. 
The following apply herein: 
Lower alkyl is 1-4 carbon atoms. 
Aryl is C.sub.6 -C.sub.10, preferably phenyl or naphthyl. 
Alkyl .beta.-cyanoacrylate is 1-8 carbon atoms in the alkyl group. 
Arylalkyl is 7-14 carbon atoms. 
Heteroaryl is a group of 3-10 atoms selected from C, O, S and N, with at 
least one atom being O, S or N. 
Heteroarylalkyl is a heteroaryl group attached to an alkyl of 1-8 carbon 
atoms. 
Alkylene is 2-8 carbon atoms. 
Monosaccharide is a 3, 4, 5, 6 or 7-carbon sugar such as glucose, ribose, 
or rhamnose. 
Alkylcarbonyloxy contains an alkyl group of 1-8 carbons. 
V. General Description of Synthetic Processes 
Compounds of the invention are prepared by the general processes described 
below. 
Two general synthetic routes were employed to prepare the fused 
pyrrolocarbazoles of the invention (FIGS. 2 and 3). Method A (FIG. 2) uses 
an indole derivative (IV) which is either unsubstituted or substituted at 
carbons 4-7 (inclusive). The indole derivatives are prepared using 
standard methodology (U.S. Pat. Nos. 3,976,639; 3,732,245; The Chemistry 
of Heterocyclic Compounds, Indoles Parts One and Two; Houlihan Ed., 
Wiley-Interscience (1972)). In Method A (FIG. 2), 1H-indole or a 
derivative thereof is protected as a lithium indole-1-carboxylate 
intermediate (Tetrahedron Lett. 26:5935 (1985)), then treated with a 
strong base, such as t-BuLi, then alkylated with an appropriate 2-indanone 
derivative to give the corresponding tertiary alcohol V. The 2-indanone 
derivatives can be prepared using previously described procedures (see 
U.S. Pat. Nos. 4,192,888; 4,128,666; J. Am. Chem. Soc. 89:4524 (1967); 
Tetrahedron Lett. 43:3789 (1974); Chem. Ber. 122:1791 (1989); Can. J. 
Chem. 60:2678 (1982); Helvetica Chimica Acta 70:1791 (1987); Chem. Pharm. 
Bull. 33:3336 (1985); J. Org. Chem. 55:4835 (1990); Tetrahedron 45:1441 
(1989); Synthesis 818 (1981)). The resulting tertiary alcohol V is treated 
with a dilute acid (e.g., 2N HCl in acetone) to give the corresponding 
2-(2-indenyl)indole VI. Alternatively, the starting 1H-indole derivative 
described previously is converted to a 1-substituted indole derivative 
(IV; R.sup.2 not .dbd.H) by standard methodology, for example, by 
treatment of the 1H-indole with base and an alkylating agent to give a 
1-substituted indole. In these examples, the indole derivative can be 
directly treated with a strong base (e.g., t-BuLi, sec-BuLi, n-BuLi, 
lithium diisopropylamide) followed by alkylation with a 2-indanone 
derivative to give the corresponding tertiary alcohol V, which includes 
substituents in position one of the indole ring. Cycloaddition reaction of 
compounds of the general formula VI with maleimide, preferably at 
temperatures of 160.degree.-200.degree. C., forms the corresponding 
tetrahydrocarbazole VII. Cycloaddition reactions of 2-(2-indenyl)indoles 
have not been described previously. Cycloaddition reactions of 2-vinyl 
indoles with maleimides are well known (U.S. Pat. No. 4,912,107 and 
references therein). Compound VII is dehydrogenated according to 
conventional processes with, for example, 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone, Pd on active charcoal, sulfur 
or sodium nitrite (U.S. Pat. No. 4,912,107 and references cited therein) 
to give the corresponding aromatized pyrrolocarbazole derivative VIII. 
Isomeric lactams of general formula IX and X can be prepared by the 
reduction of imide VIII with reducing agents (e.g., zinc amalgam, gaseous 
hydrogen chloride, zinc amalgam in acetic acid, zinc in glacial acetic 
acid, or hydride reducing agents such as lithium aluminium hydride). 
Regioisomers are separated by standard processes such as recrystallization 
or chromatography, for example, column chromatography or HPLC. The imides 
are reduced to hydroxylactams where A.sup.1, A.sup.2 or B.sup.1, B.sup.2 
.dbd.H, OH by hydride reducing agents such as borohydrides or aluminium 
hydrides (U.S. Pat. Nos. 4,192,107 and 4,923,986 and references therein). 
The resulting hydroxyl group is easily converted to alkoxy or thioalkyl 
groups (U.S. Pat. No. 4,923,986). Derivatives in which A.sup.1, A.sup.2 or 
B.sup.1, B.sup.2 together represent S or N are prepared as described in 
European Patent Application No. 0 508 792 AI. 
Method B (FIG. 3) outlines a novel method for the preparation of isomeric 
fused pyrrolocarbazole lactams (XIV, XVII). Cycloaddition reaction of a 
compound of general formula XI with ethyl .beta.at temperatures of 
160.degree.-200.degree. C., yields isomeric tetrahydrocarbazole 
cyano-esters (XII and XV). Isomers XII and XV are separated into 
regiospecific isomers by recrystallization or chromatography, e.g., column 
chromatography or HPLC. XII and XV can be separately dehydrogenated 
according to conventional methods, for example, with 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone, Pd on active charcoal, sulfur 
or sodium nitrite (U.S. Pat. No. 4,912,107 and references cited therein), 
to give the corresponding aromatized pyrrolocarbazole derivative (XIII or 
XVI). Regiospecific lactams of the general structures XIV and XVII (FIG. 
3) can be separately prepared by reductive-cyclization of the 
corresponding nitrile-esters XIII or XVI by using reducing agents, for 
example, Raney Nickel/H.sub.2, PdO, or Pd on activated charcoal. 
Fused pyrrolocarbazole derivatives of Formula I in which X.dbd.CH.sub.2 
CH.sub.2, XIX, or CH.dbd.CH, XX are prepared by the procedures described 
for Methods A and B (FIGS. 2 and 3), except the 2-indanone compound was 
replaced with a 2-tetralone. The 2-tetralone compound can be prepared by 
using standard procedures (J. Med. Chem. 32:2128 (1989); J. Med. Chem. 
36:2279 (1993); J. Med. Chem. 36:2485 (1993); Tetrahedron Lett. 14:951 
(1971); J. Org. Chem. 33:4288 (1968); J. Org. Chem. 26:4232 (1961); J. 
Med. Chem. 25:1358 (1982); Synth. Commun. 21:981 (1991); WO 92/06967, WO 
92/16524, and WO 90/15047). FIG. 4 shows a fused pyrrolocarbazole 
derivative in which X is CH.sub.2 CH.sub.2 (XVIII). Partial 
dehydrogenation of XVIII with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in 
toluene at 65.degree. C. gives the corresponding dihydronaphthyl 
derivative XIX. Treatment of XVIII with 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone in dioxane at reflux 
temperatures gives the corresponding fully dehydrogenated naphthyl 
derivative XX. Replacement of the 2-indanone compound with a 
2-benzosuberone derivative (J. Am. Chem. Soc. 13:1344, (1991); J. Org. 
Chem. 44:1342 (1979)) gives fused pyrrolocarbazoles of general structure 
I, where X.dbd.CH.sub.2 CH.sub.2 CH.sub.2. Ketone derivatives where X is 
C.dbd.O can be prepared by oxidation of either the imide or lactam of I by 
using standard oxidizing reagents (e.g., SeO.sub.2, CrO.sub.3, Na.sub.2 
CrO.sub.7, or MnO.sub.2). 
Compounds in which X.dbd.S, O, or C.dbd.O (general structure XXII) can be 
prepared by cycloaddition reactions as described in Methods A and B (FIGS. 
2 and 3). For example, the compounds 2-(2-(1-oxoindenyl)indole, 
2-(2-benzothienyl)indole, 2-(2-indenyl)indole, and 
2-(2-benzofuranyl)indole may each be prepared by coupling 
1-carboxy-2-tributylstannylindole (XXI) with 2-bromobenzothiophene, 
2-bromobenzofuran, or 1-oxo-2-(trifluoromethanesulfonate)indene (FIG. 5) 
by using standard published procedures (Angew. Chem. Int. Ed. Engl. 25:508 
(1986); J. Am. Chem. Soc. 109:5478 (1987); Tetrahedron Lett. 37:4407 
(1986)). Preparation of a carbazole is also achieved by treatment of 
2-(2-benzothienyl)indole or 2-(2-benzofuranyl)indole (XVII, where X.dbd.S 
or O, respectively) with maleimide or ethyl .beta.-cyanoacrylate in the 
presence of an acidic catalyst such as trifluoroacetic acid which gives a 
compound of general formula XXIII (FIG. 6). These compounds can be 
cyclized to form the corresponding fused pyrrolocarbazole (general 
structure XXIV) by treatment with a catalyst, for example, Pd(OAc).sub.2 
in glacial acetic acid. 
The palladium-catalyzed cross-coupling methodology is used to prepare other 
derivatives, for example, where X in FIG. 6 has 1-3 carbons (inclusive), 
by coupling the 2-(trifluoromethanesulfonate) derivative of the 
corresponding cyclic ketone with 1-carboxy-2-tributylstannylindole. 
Lactam isomers of general formulae XIV and XVII, in which R.sup.2 is 
hydrogen, can be alkylated in the presence of base (e.g., hydrides, 
alkoxides, hydroxides of alkali or alkaline earth metals, or of 
organo-lithium compounds) by treatment with R.sup.2 L in which L is a 
leaving group such as a halogen. The resulting fused pyrrolocarbazole has 
an alkyl group bound to the indole nitrogen (AU-A-29607 and U.S. Pat. No. 
4,912,107). A sugar group can be added to the indole nitrogen as described 
(European Patent Application No. 0 602 597 A2). 
Imides of the general formula XX in which the imide nitrogen is bound by 
hydrogen can be converted to an R.sup.1 group as described for I (U.S. 
Pat. No. 4,923,986). Lactam isomers with derivatives other than R.sup.1 
.dbd.H are prepared by processes described in Method A. 
Imides of general formula I in which R.sup.3, R.sup.4, R.sup.5, or R.sup.6 
substituents are other than H are prepared by the procedures described 
(U.S. Pat. No. 4,923,986) or by using standard methods known to those 
skilled in the art of organic chemistry. 
A. Specific Description of Synthetic Processes 
FIG. 2: Synthesis of Fused Pyrrolocarbazoles (Method A) 
Part IA. 
Step-1A: Preparation of 2-(2-(2-Hydroxy)indanyl)indole (FIG. 2, V, R.sup.2, 
R.sup.3 .dbd.H, X.dbd.CH.sub.2) 
n-BuLi (107.5 mmol, 43 mL of 2.5M solution in hexanes) was added dropwise 
(15 min) to a solution (12.0 g, 102.4 mmol) of indole (FIG. 2 I, R.sup.2, 
R.sup.3 .dbd.H) in dry THF (400 mL) at -78.degree. C. (nitrogen 
atmosphere). The solution was stirred for 30 min, then CO.sub.2 (g) was 
passed through the solution for 10 min. The clear solution was allowed to 
warm to ambient temperature, then it was concentrated to half the original 
volume at reduced pressure. THF (200 mL) was added and the solution 
re-cooled to -78.degree. C. At this point, t-BuLi (102 mmol, 60 mL of 1.7M 
solution in hexanes) was added dropwise (45 min). The resulting yellow 
solution was allowed to stir for 2 h at -78.degree. C. Next, 2-Indanone 
(15.0 g, 112.6 mmol) in THF (100 mL) was added dropwise (30 min) and the 
mixture stirred for 1 hour. The reaction was quenched by addition of water 
(5 mL); the resulting mixture was poured into saturated NH.sub.4 Cl 
solution (250 mL), and then extracted with ether (1.times.200 mL). The 
ether layer was washed with 100 mL saturated NH.sub.4 Cl, dried 
(MgSO.sub.4), and concentrated at reduced pressure to give an oily 
product. The product (V) was recrystallized from Et.sub.2 O-hexane to give 
10.5 g of a tan powder with an mp of 244.degree.-245.degree. C. The 
following NMR data were obtained: .sup.1 H NMR (CDCl.sub.3): .delta. 2.4 
(bs, 1H), 3.3 (d, 2H), 3.6 (d, 2H), 6.4 (s, 1H), 7.1-7.4 (m, 7H), 7.6 (d, 
1H), 8.6 (bs, 1). Anal. calc. C.sub.17 H.sub.15 NO; C, 81.90; H, 6.06; N, 
5.62. Found C, 82.16; H, 6.03; N, 5.58. 
The mother liquor was concentrated to yield an oily product. Column 
chromatography (silica gel, EtOAc:hexane 1.2) yielded an additional 2.1 g 
of product for a total yield of 12.6 g (49%). 
Step-2A: Preparation of 2-(2-Indenyl)indole (FIG. 2, VI) 
To a stirred solution of 2-(2-(2-hydroxy)indanyl)indole (FIG. 2, V, 
R.sup.2, R.sup.3 .dbd.H, X.dbd.CH.sub.2) (4.0 g, 16.1 mmol) in acetone (30 
mL) was added 2N HCl (10 mL). The mixture was stirred at ambient 
temperature for 1 hour. About 20 mLs of water were added and the 
precipitate collected by filtration. The filtrate was washed well with 
water and dried to give 3.6 g (98%) of a white solid product with an mp of 
273.degree.-274.degree. C. (MeOH). The following NMR data were obtained: 
.sup.1 H NMR (CDCl.sub.3): .delta. 3.9 (s, 2H), 6.7 (s, 1H), 7.0-7.6 (m, 
9H), 8.3 (bs, 1H). Anal. calc. C.sub.17 H.sub.13 N, C, 88.28; H, 5.67; N, 
6.06. Found C, 88.11; H, 5.60; N, 5.98. 
Step-3A: Preparation of 
4c,7a,7b,12a-Tetrahydro-6H,12H,13H-indeno[2,3-a]pyrrolo 
[3,4-c]carbazole-5,7-(5H,7H)dione (FIG. 2 VII, R.sup.2, R.sup.3, R.dbd.H, 
X.dbd.CH.sub.2). 
A mixture of 2-(2-indenyl)indole (FIG. 2, VI, R, R.sup.2, R.sup.3 .dbd.H, 
X.dbd.CH.sub.2) (1.0 g, 4.3 mmol) and maleimide (525 mg, 5.41 mmol) in a 
10 cm sealed reaction vial was heated at 180.degree.-190.degree. C. for 30 
min. After cooling the reaction to ambient temperature, MeOH (5 mL) was 
added. The product (VII) was collected to give 880 mg (62%) of a white 
solid product with amp of 254.degree.-255.degree. C. (MeOH). The following 
NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 
3.1-3.4 (m, 2H), 3.8 (m, 2H), 3.95 (t, 1H), 4.35 (d, 1H), 6.9-7.4 (m, 7H), 
7.75 (d, 1H), 11.05 (s, 1H), 11.25 (s, 1H). 
EXAMPLE V(A)(1) 
Step-4A: Preparation of 
6H,12H,13H-Indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)-dione (FIG. 2, 
VIII, Compound I-1) 
Compound VII (FIG. 2, R.sup.2, R.sup.3, R.dbd.H) (800 mg, 2.44 mmol) was 
dissolved in toluene (60 mL). Solid 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (1.4 g, 6.1 mmol) was added to 
the toluene solution in one portion. The solution was maintained at 
60.degree.-65.degree. C. for 6 hours. After cooling on an ice bath, the 
solid product was collected by filtration, resuspended in MeOH (20 mL) and 
collected by filtration. The product (VIII) was recrystallized from 
acetone-MeOH to yield 710 mg (90%) of a yellow solid product with a mp 
greater than 330.degree. C. The following NMR data were obtained: .sup.1 H 
NMR (DMSO-d.sub.6, 300 MHz): .delta. 4.3 (s, 2H), 7.35 (t, 1H), 7.45-7.65 
(m, 4H), 7.75 (d, 1H), 8.95 (d, 1H), 9.1 (d, 1H), 11.15 (s, 1H), 12.3 (s, 
1H). MS(FAB): m/e 325 (m+1).sup.+. Anal. calc. for C.sub.21 H.sub.12 
N.sub.2 O.sub.2. 0.75 H.sub.2 O: C, 74.65; H, 4.03; N, 8.29. Found; C, 
74.40; H, 3.75; N, 8.26. 
EXAMPLES V(A)(2) AND (3) 
Preparation of 6H,7H,12H,13H-Indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one 
(FIG. 2, IX, Compound I-3) and 
5H,6H,12H,13H-Indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one (FIG. 2, X, 
Compound I-2) 
A stirred suspension of Zn dust (5 g) and mercuric chloride (1 g) was made 
in 10 mL water. Concentrated hydrochloric acid (2ml) was added dropwise. 
After 10 min, the aqueous layer was decanted and removed. The zinc amalgam 
obtained was first washed with water, then repeatedly with EtOH. The zinc 
amalgam was suspended in EtOH (75 mL). Next, solid Compound VIII (500 mg, 
1.5 mmol, R, R.sup.2, R.sup.3 .dbd.H, X.dbd.CH.sub.2)) was added in one 
portion. HCl(g) was passed through as the mixture was maintained at reflux 
for 2 hours. After cooling to ambient temperature, the solution was 
concentrated at reduced pressure to yield an oily product. THF-EtOAc (200 
mL, 1:1) was added to the oily product and the mixture was extracted with 
a saturated NaHCO.sub.3 solution (3.times.100 mL), saturated NaCl solution 
(3.times.100 mL) and the resulting solution dried (MgSO.sub.4). The drying 
agent was removed, and the solvent was concentrated at reduced pressure to 
give a crude solid. Purification by column chromatography (silica gel, 
95:5, EtOAc:MeOH) yielded 240 mg (50%) of a 4:1 mixture of Compound I-3 
and I-2. The following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 
300 MHz): .delta. 4.15 (s, 1.6H), 4.25 (s, 0.4H), 4.9 (s, 0.4H), 4.95 (s, 
1.6H), 7.2-7.8 (m, 6H), 8.0 (d, 1H), 8.6 (s, 0.8H), 8.8 (s, 0.2H), 9.2 (d, 
0.2H), 9.4 (d, 0.8H), 11.8 (s, 0.2H), 11.95 (s, 0.8H). MS(FAB): m/e 311 
(m+1).sup.+ 
B. Specific Description of Synthetic Processes 
FIG. 3: Synthesis of Fused Pyrrolocarbazoles (Method B) 
Part IIB. 
Step-1B: Preparation of 
3-Cyano-4-ethoxycarbonyl-1,2,3,4-tetrahydro-[1H]indeno[2,3-a]9H-carbazole 
(XII) and 
4-Cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro-[1H]indeno[2,3-a]9H-carbazole 
(XV) 
Step-1: A mixture of2-(2-indenyl)indole (VI) (R.sup.2, R.sup.3, R.sup.4, 
R.sup.5, R.sup.6 .dbd.H, X.dbd.CH.sub.2, 3.5 g, 15.2 mmol) and ethyl 
cis-[3-cyanoacrylate (10 g, 80 mmol) in a sealed reaction flask, was 
heated to 190.degree. C. with stirring for 1.5 hours. The mixture was 
cooled to ambient temperature, MeOH (20 mL) was added and the solution was 
cooled to -20.degree. C. Compound XV was collected from the filtrate to 
give 1.65 g (31%) of a light yellow solid with an mp of 
270.degree.-272.degree. C. (acetone-MeOH). The following NMR data were 
obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 1.3 (t, 3H), 
3.1-3.4 (m, 3H), 3.7 (m, 1H), 3.9 (t, 1H), 4.4 (m, 2H), 4.6 (d, 1H), 
6.95-7.2 (m, 6H), 7.3 (d, 1H), 7.45 (d, 1H), 11.3 (s, 1H). IR (KBr) 
cm.sup.-1 : 2210 (CN); 1690 (C.dbd.O). MS(FAB): m/e 356 (m.sup.+). 
The filtrate XV was concentrated at reduced pressure to yield a viscous 
oily product. The excess ethyl cis-.beta.-cyanoacrylate was removed by 
Kugelrohr distillation (oven temperature 80.degree.-85.degree. C., 0.5 
mm). Ether was added and the Compound XII (R.sup.2, R.sup.3, R.sup.4, 
R.sup.5, R.sup.6 .dbd.H, X=CH2) was crystallized from the residue to give 
650 mg (12%) of an off-white solid with an mp of 206.degree.-207.degree. 
C. (acetone-MeOH). The following NMR data were obtained: .sup.1 H NMR 
(DMSO-d.sub.6 300MHz): .delta. 1.15 (t, 3H), 3.1-3.25 (m, 1H), 3.4-3.5 (m, 
1H), 3.8 (q, 1H), 3.9 (m, 1H), 4.05 (t, 1H), 4.2-4.3 (m, 3H), 6.95 (t, 
1H), 7.1 (t, 1H), 7.2-7.4 (m, 5H), 7.55 (m, 1H), 11.35 (s, 1H). MS(FAB): 
m/e=356 (M.sup.+). 
Step-2B: Preparation of 3 -Cyano-4-ethoxycarbonyl-indeno 
[2,3-a]9H-carbazole (FIG. 3, XIII (R.sup.2, R.sup.3, R.sup.4, R.sup.5, 
R.sup.6 .dbd.H, X.dbd.CH.sub.2)) 
Compound XII (400 mg, 1.12 mmol) was dissolved in dry toluene (50 mL). 
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (640 mg, 2.8 mmol) was added to 
the stirred solution in one portion. The solution was stirred at 
60.degree.-65.degree. C. for 6 hours. After cooling on an ice bath, the 
precipitate was collected by filtration, the product was suspended in MeOH 
(20 mL), collected and washed with cold MeOH (10 mL) to yield 355 mg (90%) 
of a light green solid with an mp of 292.degree.-293.degree. C. (acetone). 
The following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 
MHz): .delta. 1.4 (t, 3H), 4.3 (s, 2H), 4.7 (q, 2H), 7.3 (m, 1H), 7.4-7.7 
(m, 4H), 7.8 (d, 1H), 8.05 (d, 1H), 8.45 (d, 1H), 12.5 (s, 1H). IR (KBr) 
cm.sup.-1 : 2210 (CN); 1710 (C.dbd.O). MS(FAB): m/e 353 (m+1).sup.+. Anal. 
calc. C.sub.23 H.sub.16 N.sub.2 O.sub.2 : C, 78.39; H, 4.58; N, 7.95. 
Found: C, 78.61; H, 4.28; N, 7.75. 
EXAMPLE V(B)(1) 
Step-3B: Preparation of 
6H,7H,12H,13H-Indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one (FIG. 3, XIV, 
Compound I-3) 
A mixture of Compound XIII (300 mg; 0.85 mmol) and Raney Nickel catalyst 
(ca. 1 g, wet form) in MeOH/THF (125/25 mL) was hydrogenated at 35 psi on 
a Parr Apparatus for 12 hours. The resulting solution was diluted with THF 
(50 mL), and then filtered through celite. The solvent was concentrated at 
reduced pressure and the product purified by column chromatography (silica 
gel; EtOAc:Hex; 2:1, R.sub.f =0.3). The product fractions were collected 
and concentrated to give a white solid. This solid was triturated with 
MeOH (10 mL), collected by filtration and dried (100.degree. C., 0.5 mm, 
12 hours) to give 140 mg (53%) of Compound I-3 as a white solid with a nip 
of greater than 300.degree. C. (THF-MeOH). The following NMR data were 
obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz) .delta. 4.25 (s, 2H), 4.9 
(s, 2H), 7.2 (t, 1H), 7.35-7.5 (m, 3H), 7.6 (d, 1H), 7.8 (t, 1H), 8.8 (s, 
1H), 9.2 (d, 1H), 11.85 (s, 1H). MS(FAB): m/e=311 (M+1).sup.+. Anal. 
calc.: C.sub.21 H.sub.14 N.sub.2 O.0.4 H.sub.2 O; C, 79.42; H, 4.65; N, 
8.82. Found: C, 79.54; H, 4.60; N, 8.70. 
Step-4B: Preparation of 4-Cyano-3-ethoxycarbonyl-indeno[2,3-a]9H-carbazole 
(FIG. 3, XVI, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 .dbd.H, 
X.dbd.CH.sub.2)) 
To a stirred solution of Compound XV (1.1 g, 3.1 mmol; R.sup.2, R.sup.3, 
R.sup.4, R.sup.5, R.sup.6 .dbd.H, X.dbd.CH.sub.2)) in dry toluene (70 mL) 
was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (1.75 g, 7.7 mmol) in 
one portion. The solution was stirred at 60.degree.-65.degree. C. for 6 
hours. After cooling on an ice bath, the precipitate was collected by 
filtration, the product was suspended in MeOH (40 mL), collected and 
washed with cold MeOH (10 mL) to give 975 mg (89%) of a light green solid 
(XVI; R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6 .dbd.H, X.dbd.CH.sub.2) 
with an mp of 260.degree.-263.degree. C. (acetone). The following NMR data 
were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 1.4 (t, 3H), 
4.35 (s, 2H), 4.6 (q, 2H), 7.3-7.5 (m, 3H), 7.55-7.8 (m, 5H), 8.5 (d, 1H), 
12.6(s, 1H). IR (KBr) cm.sup.-1 : 2210(CN); 1710(C.dbd.O). MS(FAB): m/e 
353 (m+1).sup.+. Anal. calc. C.sub.23 H.sub.16 N.sub.2 O.sub.2 : C, 78.39; 
H, 4.58; N, 7.95. Found: C, 78.77; H, 4.39; N, 7.71. 
EXAMPLE V(B)(2) 
Step-5B: Preparation of 
6H,7H,12H,13H-Indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one 
A mixture of Compound XVI (170 mg, 0.5 mmol) and Raney Nickel catalyst 
(approx. 500 mg, wet form) in MeOH/THF (3:1 75 mL) was hydrogenated at 35 
psi on a Parr Apparatus for 12 hours. The solvent was diluted with THF (50 
mL), and then filtered through celite. The solvent was concentrated at 
reduced pressure and the product was purified by column chromatography 
(silica gel, EtOAc:hexane, 2:1, R.sub.f =0.3) to yield 115 mg (77%) of an 
off-white solid (XVII, compound I-2), mp&gt;300.degree. C. (THF-MeOH). The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 4.15 (s, 2H), 4.95 (s, 2H), 7.2-7.5 (m, 4H), 7.65 (d, 1H), 7.7 (d, 
1H), 8.0 (d, 1H), 8.6 (s, 1H), 9.4 (d, 1H), 11.95 (s, 1H). MS(FAB): m/e 
311 (m+1).sup.+. Anal. calc. for: C.sub.21 H.sub.14 N.sub.2 O.0.4 H.sub.2 
O; C, 79.42; H, 4.65; N, 8.82. Found: C, 79.61; H, 4.56; N, 8.63. 
C. Specific Description of Synthetic Processes 
Preparation of Halogenated Fused Pyrrolocarbazoles 
Part IIIA. Fluorinated Derivatives 
Step-1A: Preparation of 5-Fluoro-2-(2-(2-hydroxy)indanyl)indole: 
This compound was prepared using substantially the same procedure as in 
Part IA, Step-1A, except that 5-fluoroindole was substituted for I. 
5-Fluoro-2-(2-(2-hydroxy)indanyl)indole; yield 64%, mp 
158.degree.-161.degree. C. dec (MeOH-ether). The following NMR data were 
obtained: .sup.1 H NMR (CDCl.sub.3, 300 MHz): .delta. 2.2 (bs, 1H), 3.35 
(d, 2H), 3.6 (d, 2H), 6.4 (s, 1H), 6.95 (t, 1H), 7.2-7.35 (m, 6H), 8.6 
(bs, 1H). Anal. calc. for: C.sub.17 H.sub.14 FNO; C, 76.36; H, 5.28; N, 
5.24. Found: C, 76.70; H, 5.20; N, 5.08. 
Step-2A: Preparation of 5-Fluoro-2-(2-indenyl)indole: 
This compound was prepared by substantially the same procedure as in Part 
IA, Step-2A. 
5-Fluoro-2-(2-indenyl)indole; yield 95%, mp 233.degree.-236.degree. C. dec 
(MeOH-ether). The following NMR data were obtained: .sup.1 H NMR 
(CDCl.sub.3, 300 MHz): .delta. 3.85 (s, 2H),6.65 (s, 1H), 6.9-7.5 (m, 9H), 
8.3 (s, 1H). Anal. calc. for: C.sub.17 H.sub.12 FNO; C, 81.91; H, 4.85; N, 
5.62. Found: C, 81.60; H, 4.75; N, 5.54. 
Step-3A: Preparation of 
3-Fluoro-4c,7a,7b,12a-tetrahydro-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]car 
bazole-5,7(5H,7H)-dione 
A mixture of 5-fluoro-2-(2-indenyl)indole (365 mg, 1.45 mmol) and maleimide 
(215 mg, 2.2 mmol) in a 10 cm sealed reaction vial was heated at 
180.degree.-190.degree. C. for 30 min. After cooling the reaction to 
ambient temperature, ice-cold CH.sub.3 OH (4 mL) was added. The resulting 
crystals were collected by filtration to give 275 mg (55%) of product with 
an mp of 272.degree.-275.degree. C. (acetone-MeOH). The following NMR data 
were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 3.1-3.4 (m, 
2H), 3.7-3.8 (m, 2H), 3.95 (m, 1H), 4.3 (d, 1H), 6.9 (m, 1H), 7.1-7.3 (m, 
5H), 7.4 (d, 1H), 11.2-11.3 (d, 2H). 
EXAMPLE V(C)(1) 
Step-4A: Preparation of 
3-Fluoro-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione 
(Compound I-7). 
To a solution of 3-fluoro-4c,7a,7b,12a-tetrahydro-6H, 12H, 
13H-Indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione (Part IIIA, 
Step-3) (250 mg, 0.73 mmol) in toluene (25 mL) was added solid 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (410 mg, 1.8 mmol) in one 
portion. The mixture was heated at 45.degree. C. for 6 hours. After 
cooling on an ice-bath, the precipitate was collected by filtration, and 
then resuspended in MeOH (10 mL). The product was collected by filtration 
and washed with cold MeOH (1.times.5 mL). Recrystallization from 
THF-MeOH-Et.sub.2 O gave 215 mg (86% yield) of Compound I-7. Compound I-7 
exhibited an mp of greater than 275.degree. C. The following NMR data were 
obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 4.25 (s, 2H); 
7.35-7.55 (m, 3H); 7.65 (m, 1H); 7.75 (d, 1H); 8.6 (d, 1H): 9.1 (d, 1H); 
11.3 (s, 1H); 12.35 (s, 1H). MS(FAB): m/e 343 (m+1).sup.+ 
EXAMPLE V(C)(2) 
Step-5A: Preparation of 
3-Fluoro-6H,7H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one and 
3-fluoro-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-8) 
A stirred suspension of Zn dust (1.3 g) and mercuric chloride (200 mg) in 
water (3 mL) was made and 0.5 mL concentrated hydrochloric acid was added 
dropwise. After five minutes, the aqueous layer was decanted. The zinc 
amalgam was first washed with water, then washed repeatedly with EtOH. The 
zinc amalgam was suspended in EtOH (20 mL), and 75 mg, (0.22 mmol) solid 
Compound I-7 was added in one portion. HCl(g) was passed through the 
solution while the solution was maintained at reflux for 1 hour. After 
cooling to ambient temperature, the solution was concentrated at reduced 
pressure to give a crude solid. The solid was dissolved in THF-EtOAc (1:1, 
100 mL) and extracted with saturated NaHCO.sub.3 (2.times.100 mL), 
saturated NaCl solution (3.times.100 mL), and then dried (MgSO.sub.4). The 
drying agent was removed by filtration and the solvent concentrated at 
reduced pressure. The product was purified by column chromatography 
(silica gel, 2:1, EtOAc:hexanes) R.sub.f =0.3; to give 20 mg (28% yield) 
of the Compound I-8 mixture. The mixture exhibited an mp of greater than 
300.degree. C. The following NMR data were obtained: .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): .delta. 4.15 (s, 1.34H); 4.25 (s, 0.66H); 4.9 (s, 
0.66H); 4.95 (s, 1.34H); 7.2-7.85 (m, 6H); 8.6 (s, 0.67H); 8.85 (s, 
0.33H); 8.9 (d, 0.33H); 9.4 (d, 0.67H); 11.95 (s, 0.33H); 12.0 (s, 0.67H). 
MS(FAB): m/e 329 (m+1).sup.+. 
EXAMPLE V(C)(3) 
(Method B) 
Step-1B: Preparation of 
6-Fluoro-4-cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro[1H]indeno[2,3-a]9H-ca 
rbazole 
A mixture of 5-fluoro-2-(2-(2-hydroxy)indanyl)indole (Part IIIA, Step IA 
1.5 g, 6.0 mmol) and ethyl cis-b-cyanoacrylate (10.0 g, 80 mmol), in a 
sealed reaction flask, was heated at 180.degree. C. with stirring for 1.5 
hours. The mixture was cooled to ambient temperature, MeOH (10 mL) was 
added and the solution cooled to -20.degree. C. The product was collected 
to give 650 mg (29% yield) of a light tan solid with an mp of 
301.degree.-305.degree. C. (MeOH). The following NMR data were obtained: 
.sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 1.3 (t, 3H), 3.1-3.35 (m, 
3H), 3.75 (s, m, 4H), 3.95 (m, 1H), 4.4 (q, 2H), 4.65 (d, 1H), 6.9-7.0(m, 
1H), 7.02-7.4 (m, 6H), 11.4 (s, 1H). IR(KBr) cm.sup.-1 : 2210(CN); 1690 
(C.dbd.O). 
Step-2B: Preparation of 
6-Fluoro-4-cyano-3-ethoxycarbonyl[1H]indeno[2,3-a]9H-carbazole 
To a stirred solution of 
6-fluoro-4-cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro-[1H]-indeno[2,3-a]9H- 
carbazole (Example V(C)3, Step-1B) (400 mg, 1.1 mmol) in dry toluene (40 
mL) was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (600 mg, 2.7 mmol) 
in one portion. The solution was stirred at 65.degree.-70.degree. C. for 6 
hours. After cooling on an ice bath the precipitate was collected by 
filtration, the product was suspended in MeOH (20 mL), collected again, 
then washed with cold MeOH (10 mL) to give 375 mg (92% yield) of a light 
yellow product with an mp of 256.degree.-258.degree. C. (acetone). The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 1.4 (t, 3H), 4.3 (s, 2H), 4.7 (q, 2H), 7.0 (m, 1H), 7.1 (m, 1H), 
7.15 (m, 1H), 7.4-7.9 (m, 4H), 12.5 (s, 1H). IR (KBr) cm.sup.-1 : 2210 
(CN); 1710 (C.dbd.O). MS(FAB): m/e 370 (m).sup.+. 
Step-3B: Preparation of 
3-Fluoro-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-12) 
A mixture of 
6-fluoro-4-cyano-3-ethoxycarbonyl-[1H]-indeno[2,3-a]9H-carbazole (Example 
V(C)3, Step-2B): (100 mg, 0.27 mmol) and Raney Nickel catalyst (approx. 
500 mg, wet form) in THF/MeOH (50 mL) was hydrogenated at 35 psi on a Parr 
Apparatus for 12 hours. THF (50 mL) was added and the solvent filtered 
through Celite.RTM. diatomaceous earth and concentrated at reduced 
pressure. The product was purified by column chromatography (silica gel, 
EtOAc:hexane, 2:1, R.sub.f =0.3) to give 15 mg (17% yield) of Compound 
I-12 as an off-white solid. Compound I-12 exhibited an mp of greater than 
300.degree. C. The following NMR data were obtained: .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): .delta. 4.18 (s, 2H), 4.95 (s, 2H), 7.3-7.45 (m, 
4H), 7.6-7.75 (m, 2H), 7.83 (d, 1H), 8.6 (s, 1H), 9.4 (d, 1H); 12.0(s, 
1H). MS(FAB): m/e 329 (m+1).sup.+. 
EXAMPLE V(C)(4) 
Preparation of 3-Fluoro-6H,7H12H,13 
H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one (Compound I-23) 
To a stirred solution of 
6-fluoro-4-cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro-[1H]-indeno[2,3-a]9H- 
carbazole (Example V(C)3, step-2B) (230 mg, 0.6 mmol) in dry toluene (25 
mL) was added 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (340 mg, 1.5 mmol) 
in one portion. The solution was stirred at 65.degree.-70.degree. C. for 6 
hours. After cooling on an ice bath, the precipitate was collected by 
filtration, the product was suspended in MeOH (20 mL), collected and 
washed with cold MeOH (10 mL) to yield 160 mg (70%) of a light yellow 
solid. The melting point was &gt;300.degree. C. (acetone). The following NMR 
data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 1.45 (t, 
3H, J=6 Hz), 4.3 (s, 2H), 4.65 (q, 2H, J=6 Hz), 7.4-7.6 (m, 3H), 7.62-7.68 
(m, 1H), 7.75-7.82 (m, 2H), 8.5 (d, 1H, J=8 Hz), 12.55 (s, 1H). IR (KBr) 
cm.sup.-1 : 2210(CN); 1710(C.dbd.O). MS(FAB): m/e 370(m).sup.+. 
Preparation of 
3-Fluoro-6H,7H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one 
(Compound I-23) 
A mixture of 
6-fluoro-4-cyano-3-ethoxycarbonyl-[1H]-indeno[2,3-a]9H-carbazole (125 mg, 
0.34 mmol; Example V(C)3, Step-3B) and Raney Nickel catalyst (approx. 500 
mg, wet form) in THF (50 mL) was hydrogenated at 35 psi on a Parr 
Apparatus for 12 hours. THF (50 mL) was added and then the solution was 
filtered through Celite.RTM. and concentrated at reduced pressure to give 
75 mg of crude product. The product was purified by HPLC to give Compound 
I-23 as a white solid. The melting point was greater than 300.degree. C. 
The following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 
MHz): .delta. 4.26 (s, 2H), 4.9 (s, 2H), 7.25-7.60 (m, 4H), 7.75-8.05 (m, 
2H), 8.83 (s, 1H), 8.9 (d, 1H, J=10 Hz), 11.88 (s, 1H). MS(FAB): m/e 329 
(m+1).sup.+. 
D. Specific Description of Synthetic Processes 
Preparation of Chlorinated Fused Pyrrolocarbazoles 
Part IIIB. Chlorinated Derivatives 
Step-1A: Preparation of 6-Chloro-2-(2-(2-hydroxy)indole: 
This compound was prepared by substantially the same procedure as Part IA, 
Step 1A, except that 6-chloroindole was substituted for I. 
6-Chloro-2-(2-(2-hydroxy)indanyl)indole: yield (24%); mp 
202.degree.-204.degree. C. (MeOH-ether). The following NMR data were 
obtained: .sup.1 H NMR (CDCl.sub.3, 300 MHz): .delta. 2.35 (s, 1H), 3.35 
(d, 2H), 3.6 (d, 2H), 6.4 (s, 1H), 7.05 (d, 1H), 7.2-7-4 (m, 5H), 7.45 (d, 
1H), 8.6 (s, 1H). 
Step-2A: Preparation of 6-Chloro-2-(2-indenyl)indole: 
This compound was prepared by substantially the same procedure as Part IA, 
Step-2A. 
6-Chloro-2-(2-indenyl)indole; yield 94%; mp 215.degree.-218.degree. C. dec 
(MeOH-ether). The following NMR data were obtained: .sup.1 H NMR 
(CDCl.sub.3, 300 MHz): .delta. 3.9 (s, 2H), 6.65 (s, 1H), 7.0-7.65 (m, 
8H), 8.25 (s, 1H). 
Step-3A: Preparation of 
2-Chloro-4c,7a,7b,12a-tetrahydro-12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbaz 
ole-6H-5,7-(5H,7H)-dione 
A mixture of 6-chloro-2-(2-indenyl)indole (210 mg, 0.8 mmol) and maleimide 
(160 mg, 1.7 mmol) in a 10 cm sealed reaction vial was heated at 
180.degree.-190.degree. C. for 1 hour. After the mixture was cooled to 
ambient temperature, the product was dissolved in MeOH (4 mL). Et.sub.2 O 
(5 mL) and hexane (10 mL) were added to precipitate the product as an oil. 
The oil solidified to a yellow solid product on standing. Purification by 
column chromatography (silica gel, EtOAc:hexanes, 2:1) gave 200 mg (69% 
yield) of product with an mp of greater than 225.degree. C. The following 
NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 
3.0-3.3 (m, 2H), 3.75 (m, 2H), 3.9 (t, 1H), 4.3 (d, 1H), 6.9-7.3 (m, 6H), 
7.7 (d, 1H), 11.2 (s, 1H), 11.35 (s, 1H). 
EXAMPLE V(D)(1) 
Step-4: Preparation of 
2-Chloro-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)-dione 
(Compound Ia-1) 
To a solution of 
2-chloro-4c,7a,7b,12a-tetrahydro-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]car 
bazole-5,7-(5H,7H)-dione (250 mg, 0.7 mmol) in toluene (50 mL) was added 
solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (400 mg, 1.7 mmol) in one 
portion. The mixture was stirred at 60.degree.-65.degree. C. for 4 hours. 
The solution was cooled in an ice bath and the precipitate collected by 
filtration. The product was resuspended and triturated with MeOH (10 mL). 
The product was collected and recrystallized from THF-MeOH-Et.sub.2 O to 
give 210 mg (85% yield)of Compound Ia-1 as a yellow solid product with an 
mp of greater than 300.degree. C. The following NMR data were obtained: 
.sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 4.25 (s, 2H), 7.3(d, 2H), 
7.4-7.5 (m, 2H), 7.6 (s, 1H);, 7.75 (d, 1H), 8.85 (d, 1H), 9.05 (d, 1H), 1 
1.15 (s, 1H), 12.35 (s, 1H). MS(FAB): m/e 359 (m+1).sup.+. 
EXAMPLE V(D)(2) 
Preparation of 
2-Chloro-6H,7H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one and 
2-chloro-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound Ia-2) 
To a stirred suspension of Zn dust (1.5 g) and mercuric chloride (400 mg) 
in water (5 mL) was added (dropwise) 1 mL concentrated hydrochloric acid. 
After 10 minutes, the aqueous layer was decanted. The zinc amalgam was 
first washed with water, then repeatedly with EtOH. The zinc amalgam was 
suspended in EtOH (25 mL), and solid Compound II-1 (120 mg, 0.34 mmol) was 
added in one portion. HCl(g) was passed through while the solution was 
maintained at reflux for 4 hours. After cooling to ambient temperature, 
the solution was concentrated at reduced pressure. The residue was 
dissolved in THF-EtOAc (1:1, 100 mL) and extracted with saturated 
NaHCO.sub.3 (2.times.100 mL), saturated NaCl solution (2.times.100 mL), 
and dried (MgSO.sub.4). The drying agent was removed by filtration and the 
solvent concentrated at reduced pressure to give a crude solid. The 
product was purified by column chromatography (silica gel, EtOAc:hexanes, 
2:1), R.sub.f =0.35, to give 65 mg (56% yield) of the Compound Ia-2 
mixture. The mixture exhibited an mp of greater than 300.degree. C. The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 4.15 (s, 1.6H), 4.2 (s, 0.4H), 4.9 (d, 1H), 7.2-7.5 (m, 3H), 
7.55-7.8 (m, 2H), 8.0 (d, 1H), 8.6 (s, 0.8H), 8.8 (s, 0.2H), 9.1 (d, 
0.2H), 9.4 (d, 0.8H), 11.95 (s, 0.2H), 12.05 (s, 0.8H). MS(FAB): m/e 345 
(m+1).sup.+. 
EXAMPLE V(D)(3) 
Step-1A: Preparation of 5-Chloro-2-(2-(2-hydroxy)indanyl)indole 
This compound was prepared by substantially the same procedure as Part IA, 
Step-1A except that 5-chloroindole was substituted for I. 
5-Chloro-2-(2-(2-hydroxy)indanyl)indole, yield 1.7g (36%) mp 
254.degree.-256.degree. C. (ether-hexane), .sup.1 H NMR (CDCl.sub.3) 
.delta. 2.3 (bs, 1H), 3.35 (d, 2H), 3.6 (d, 2H), 6.35 (s, 1H), 7.1-7.4 (d, 
6H), 7.6 (s, 1H), 8.6 (s, 1H). 
Step-2A: Preparation of 5-Chloro-2-(2-indenyl)indole 
This compound was prepared by substantially the same procedure as Part IA, 
Step-2A. 
5-Chloro-2-(2-indenyl)indole; yield 1.35 g (96%) mp 260.degree.-263.degree. 
C. (ether-hexane) .sup.1 H NMR (CDCl.sub.3) .delta. 3.85 (s, 2H), 6.65 (s, 
1H), 7.05 (s, 1H), 7.15 (d, 1H), 7.2-7.35 (m, 3H), 7.4 (d, 1H), 7.5 (d, 
1H), 8.25 (bs, 1H). 
Step-3A: Preparation of 
3-Chloro-4c,7a,7b,12a-tetrahydro-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]car 
bazole-5,7(5H,7H)-dione. 
A mixture of 5-chloro-2-(2-indenyl)indole (280 mg, 1.1 mmol) and maleimide 
(200 mg, 2.1 mmol) in a 10 cm sealed reaction vial was heated at 
180.degree.-190.degree. C. for 1 hour. After the mixture was cooled to 
ambient temperature, MeOH (4 mL) was added. The solution was cooled to 
-20.degree. C. and the product was collected as a white solid. 
Recrystallization from acetone-MeOH-Ether gave 250 mg as a white solid 
product (63%) mp 292.degree.-293.degree. C. The following NMR data were 
obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 3.05-3.3 (m, 2H), 
3.7-3.8 (m, 2H), 3.95 (m, 1H), 4.3 (d, 1H), 7.0-7.35 (m, 6H), 7.7 (s, 1H), 
11.3 (s, 1H), 11.4 (s, 1H). 
Step-4A: Preparation of 
3-Chloro-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)-dione 
(Compound I-10) 
Solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (345 mg, 1.52 mmol) was 
added in one portion to a solution of 
3-chloro-4c,7a,7b,12a-tetrahydro-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]car 
bazole-5,7-(5H,7H)-dione (220 mg, 0.61 mmol) in toluene (50 mL). The 
mixture was stirred at 60.degree.-65.degree. C. for 4 hours. The solution 
was cooled in an ice bath and the precipitate collected by filtration. The 
product was resuspended and tritiated with MeOH (10 mL). The product was 
collected and recrystallized from THF-MeOH-Et.sub.2 O to give 210 mg (96%) 
of Compound I-10 as a yellow solid product. The melting point was greater 
than 320.degree. C. The following NMR data were obtained: .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): .delta. 4.2 (s, 2H), 7.4-7.65 (m, 4H), 7.75 (d, 
1H), 8.89 (s, 1H), 9.05 (d, 1H), 11.3 (s, 1H); 12.4 (s, 1H). MS(FAB): m/e 
359 (m+1).sup.+. Anal. calc. for C.sub.21 H.sub.11 ClN.sub.2 O.sub.2 : C, 
69.47; H, 3.19; N, 7.72. Found C, 69.29; H, 3.04; N, 7.60. 
E. Specific Description of Synthetic Processes 
Preparation of Brominated Fused Pyrrolocarbazoles 
Part IIIC. Brominated and Iodinated Derivatives 
EXAMPLE V(E)(1) 
Preparation of 
3-Bromo-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)-dione 
(Compound I-6) 
Solid N-bromosuccinimide (55 mg, 0.31 mmol) was added in one portion to a 
stirred solution of Compound I-1 (100 mg, 0.31 mmol) in dry THF (5 mL), 
under a nitrogen atmosphere. The mixture was stirred at ambient 
temperature for 2 hours. The dark solution was diluted with EtOAc (5 mL) 
and sequentially washed with a 5% aqueous Na.sub.2 S.sub.2 O.sub.3 
solution (1.times.10 mL), water (1.times.10 mL), saturated NaCl solution 
(2.times.10 mL) and dried (MgSO.sub.4). The solvent was concentrated at 
reduced pressure to give 85 mg (68% yield) of a crude product. 
Recrystallization in THF-MeOH gave Compound I-6 as a yellow powder with an 
mp of greater than 300.degree. C. The following NMR data were obtained: 
.sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 4.25 (s, 2H), 7.4-7.8 (m, 
5H), 9.0-9.05 (d, s, 2H), 11.3 (s, 1H), 12.4 (s, 1H). MS(FAB): m/e 404 
(m+1).sup.+. 
EXAMPLE V(E)(2) 
Preparation of 
3-Bromo-6H,7H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one 
(Compound I-11) 
Solid N-bromosuccinimide (20 mg, 0.1 mmol) was added to a stirred solution 
of compound I-3 (Example V(B)(1)) (30 mg, 0.1 mmol) in dry THF (5 mL) 
under a nitrogen atmosphere. The solution was stirred at ambient 
temperature for 6 hours, then stored at -20.degree. C. for 24 hours. The 
product was collected by filtration to give 30 mg (80% yield) of Compound 
I-11 as a light yellow solid product with an mp of greater than 
340.degree. C. (THF-MeOH). The following NMR data were obtained: .sup.1 H 
NMR (DMSO-d.sub.6, 300 MHz): .delta. 4.3 (s, 2H), 4.9 (s, 2H), 7.35-7.45 
(m, 2H), 7.55 (bs, 2H), 7.7-7.85 (m, 2H), 8.9 (s, 1H), 9.35 (s, 1H), 12.05 
(s, 1H). MS(FAB): m/e 389 (m+). Anal. calc. for: C.sub.21 H.sub.13 
BrN.sub.2 O.0.4 H.sub.2 O: C, 63.50; H, 3.33; N, 6.86. Found: C, 63.61; H, 
3.51; N, 7.07. 
EXAMPLE V(E)(3) 
Preparation of 
3-Bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) 
Solid N-bromosuccinimide (20 mg, 0.1 mmol) was added to a stirred solution 
of Compound I-2 (30 mg, 0.1 mmol) in dry THF (7 mL) under a nitrogen 
atmosphere. The solution was stirred at ambient temperature 6 hours, then 
stored at -20.degree. C. for 12 hours. The product was collected by 
filtration to give 32 mg (84% yield) of a white solid (Compound I-9). 
Compound I-9 exhibited an mp of greater than 320.degree. C. (THF-MeOH). 
The following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 
MHz): .delta. 4.2 (s, 2H), 4.95 (s, 2H), 7.3-7.5 (m, 2H), 7.6 (bs, 2H), 
7.7 (d, 1H), 8.15 (s, 1H), 8.6 (s, 1H), 9.4 (d, 1H), 12.15 (s, 1H). 
MS(FAB): m/e 389 (m.sup.+). Anal. calc. for: C.sub.21 H.sub.13 BrN.sub.2 
O: C, 64.80; H, 3.37; N, 7.20. Found: C, 64.62; H, 3.63; N, 6.72. 
EXAMPLE V(E)(4) 
Step-1A: Preparation of 2-(2-(2-hydroxy-5-bromo)indanyl)indole: 
This compound was prepared by substantially the same procedure as Part IA, 
Step-1A except that 5-bromo-2-indanone was substituted for I. 
2-(2-(2-hydroxy-5-bromo)indanyl)indole yield 500 mg (31%) mp 
158.degree.-160.degree. C. (ether-hexane), .sup.1 H NMR (CDCl.sub.3) 
.delta. 2.3 (bs, 1H), 3.25-3.4 (dd, 4H), 6.4 (s, 1H), 7.1-7.4 (m, 6H), 7.6 
(d, 1H), 8.6 (s, 1H). 
Step-2A: Preparation of 2-(2-(5-bromoindenyl)indole and 
2-(2-(6-bromoindenyl)indole 
This compound was prepared by substantially the same procedure as Part IA, 
Step-2A. 
2-(2-(5-bromoindenyl)indole and 2-(2-(6-bromoindenyl)indole; .sup.1 H NMR 
(CDCl.sub.3) .delta. 3.8 (d, 2H), 6.7 (s, 0.5H), 6.95 (s, 0.5H), 7.1-7.6 
(m, 6H), 8.25 (bs, 1H). 
Step-3A: Preparation of 
4c,7a,7b,12a-Tetrahydro-6H,12H,13H-(5-bromo)indeno[2,3-a]pyrrolo[3,4-c]car 
bazole-5,7-(5H,7H)-dione and 
4c,7a,7b,12a-tetrahydro-6H,12H,13H-(6-bromo)indeno[2,3-a]pyrrolo[3,4-c]car 
bazole-5,7(5H,7H)-dione. 
A mixture containing 2-(2-(5-bromoindenyl)indole and 
2-(2-(6-bromoindenyl)indole (260 mg, 0.84 mmol) and maleimide (125 mg, 1.3 
mmol) in a 10 cm sealed reaction vial was heated at 
180.degree.-190.degree. C. for 1 hour. After the mixture was cooled to 
ambient temperature, MeOH (4 mL) was added. The solution was cooled to 
-20.degree. C. and the product was collected as a white solid product. 
Step-4A: Preparation of 
9-Bromo-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)-dione 
(Compound Ib-2) and 
10-bromo-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)-dione 
(Compound Ia-3) 
Solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (335 mg, 1.5 mmol) was 
added in one portion to a solution of the mixture containing 
4c,7a,7b,12a-tetrahydro-6H,12H,13H-5-bromoindeno[2,3-a 
]pyrrolo[3,4-c]carbazole-5,7-(5H,7H)-dione and 
4c,7a,7b,12a-tetrahydro-6H,12H,13H-6-bromoindeno[2,3-a]pyrrolo[3,4-c]carba 
zole-5,7-(5H,7H)-dione (240 mg, 0.59 mmol) in toluene (20 mL). The mixture 
was stirred at 60.degree.-65.degree. C. for 4 hours. The solution was 
cooled in an ice bath and the precipitate collected by filtration. The 
product was resuspended and triturated with MeOH (10 mL). The product was 
collected and purified by column chromatography (silica gel, EtOAc:Hexane 
1:1). 
Compound Ia-3: Rf 0.45 (10-bromo isomer). The melting point was greater 
than 300.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 4.3 (s, 
2H), 7.3 (m, 1H), 7.5-7.75 (m, 3H), 8.0 (s, 1H), 8.9-9.05 (dd, 2H), 11.25 
(s, 1H); 12.35 (s, 1H). MS(FAB): m/e 404 (m+1).sup.+. Anal. calc. for 
C.sub.21 H.sub.11 BrN.sub.2 O.sub.2.0.4 H.sub.2 O: C, 61.45; H, 2.90; N, 
6.82. Found C, 61.39; H, 2.67; N, 6.66. 
Compound Ib-2: Rf 0.4 (9-bromo isomer) mp&gt;300.degree. C. .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): .delta. 4.3 (s, 2H), 7.35 (m, 1H), 7.55-7.75 (m, 
4H), 8.95 (d, 1H), 9.3 (s, 1H), 11.3 (s, 1H); 12.35 (s, 1H). MS(FAB): m/e 
404 (m+1).sup.+. Anal. calc. for C.sub.21 H.sub.11 BrN.sub.2 O.sub.2 : C, 
62.55; H, 2.75; N, 6.95. Found C, 62.23; H, 2.71; N 6.66. 
EXAMPLE V(E)(5) 
Preparation of 
3-Iodo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)-one 
(Compound I-40) 
Step-1: Preparation of 
3-Tributylstannyl-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H) 
one 
To a solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (50 mg, 0.13 mmol), bis(tributyltin) (0.065 ml, 0.13 mmol) 
and triethylamine (1.0 mL) in DMF (11 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (32 mg). The solution was heated 
in a sealed reaction tube at 120.degree. C. for 18 h. The mixture was 
cooled to ambient temperature and solvent concentrated at reduced 
pressure. The product was purified by column chromatography (silica gel, 
EtOAc:MeOH; 1:2, Rf=0.64) to give 17 mg (20%). The compound was further 
purified by preparative TLC (silica gel, EtOAc:hexane; 3:1) to give the 
subject compound as a tan solid, mp&gt;300.degree. C. .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): d 0.88 (t, 3H), 1.13 (q, 2H), 1.33 (q, 2H), 1.58 
(q, 2H), 4.17 (s, 2H), 4.92 (s, 2H), 7.33-7.54 (m, 4H), 7.63-7.71 (m, 3H), 
8.0 (s, 1H), 8.54 (s, 1H), 9.42 (d, 1H), 11.92 (s, 1H), MS (m/e)=600 
(m+1).sup.+. 
Step-2: Preparation of Compound I-40 
To a solution of 
3-tributylstannyl-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H) 
one (Step-1) (16 mg, 0.026 mmol) in dry CH.sub.2 Cl.sub.2 (4 mL) was added 
a solution of I.sub.2 (8 mg, 2 mL CH.sub.2 Cl.sub.2) dropwise. The mixture 
was stirred at ambient temperature 2 h., then a solution of 10% 
NaHSO.sub.3 was added. After stirring for 10 min. the mixture was 
filtered. The solid was collected and washed with water, CH.sub.2 Cl.sub.2 
and dried under vacuum (100.degree. C., 6 h) to give 6 mg (53%) of 
Compound I-40, .sup.1 H NMR (DMSO-d.sub.6, 300 MHz) d 4.29 (s, 2H), 4.96 
(s, 2H), 7.33-7.50 (m, 3H), 7.66-7.79 (m, 2H), 8.29 (s, 1H), 8.62 (s, 1H), 
8.42 (d, 1H), 12.08 (s, 1H). MS (m/e)=437 (m+1).sup.+. 
EXAMPLE V(E)(6) 
Preparation of 
3-(2-Iodoethenyl)-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H) 
-one (Compound I-44) 
Step-1: Preparation of 
3-(2-Trimethylsilylethenyl-5H,6H,12H,13H-indeno2,3-a]pyrrolo[3,4-c]carbazo 
le-7(7H)one 
To a solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (400 mg, 1.0 mmol), 2-(trimethylsilylvinyl)tributylstannae 
(500 mg, 1.3 mmol) and zinc chloride (170 mg, 1.3 mmol) in DMF (5 mL) was 
added bis(triphenylphosphine)palladium(II)chloride (7 mg). The solution 
was heated in a sealed reaction tube at 100.degree. C. for 36 h. The 
mixture was cooled to ambient temperature and solvent concentrated at 
reduced pressure. The residue was triturated with hexane to give 470 (89%) 
mg of tan solid. The product was chromatographed (neutral alumina, 
THF:hexane; 1:1 to THF: hexane 2:1, Rf=0.45), and the subject compound 
crystallized in the collected fractions, mp&gt;300.degree. C. .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz) d 0.2 (s, 9H), 4.17 (s, 2H), 4.94 (s, 2H), 6.55 
(d, 1H, J=19.1 Hz), 7.12 (d, 1H, J=19.2 Hz), 7.33-7.45 (m, 4H), 7.56-7.59 
(m, 1H), 7.68 (d, 1H, J=7 Hz), 8.09 (s, 1H), 8.62 (s, 1H), 9.40 (d, 1H, 
J=7.6 Hz), 12.01 (s, 1H); MS (m/e)=431 (m+1).sup.+. 
Step-2 
To a slurry of 
3-(2-trimethylsilylethenyl-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbaz 
ole-7(7H)one (Step-1) (50 mg, 0.12 mmol) in CH.sub.2 Cl.sub.2 (3 mL) was 
added a solution of iodide (19 mg) in CH.sub.2 Cl.sub.2 dropwise. The 
mixture was stirred 4 h at ambient temperature, then concentrated at 
reduced pressure. To the residue was added a solution of 10% NaHSO.sub.3 
(2 mL), and the solution was stirred 20 h. A yellow solid was collected 
and dried to give 35 mg. A THF extract of the solid after evaporation and 
trituration with MeOH gave 10 mg of Compound I-44 as a yellow solid, 
mp&gt;300.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz) d 4.17 (s, 2H), 
4.96 (s, 2H), 7.22-7.70 (m, 7H), (m, 1H), 8.10 (s, 1H), 8.63 (s, 1H), 9.40 
(d, 1H, J=7.6 Hz), 12.04 (s, 1H); MS (m/e)=463 (m+1).sup.+. 
F. Specific Description of Synthetic Processes 
Preparation of Methylated Fused Pyrrolocarbazoles 
Part IVA. Methylated Derivatives 
EXAMPLE V(F)(1) 
Step-1A: Preparation of 2-(2-(2-Hydroxy)indanyl)-7-methylindole: 
This compound was prepared by substantially the same procedure as Part IA, 
Step-1A except that 7-methylindole was substituted for I. 
2-(2-(2-Hydroxy)indanyl)-7-methylindole: yield 11%; mp 
199.degree.-200.degree. C. The following NMR data were obtained: .sup.1 H 
NMR (CDCl.sub.3, 300 MHz): .delta. 5 2.3 (s, 1H), 2.55 (s, 3H), 3.4 (d, 
2H), 3.6 (d, 2H), 6.4 (s, 1H), 7.0 (m, 2H), 7.2-7.35 (m, 4H), 7.45 (d, 
1H), 8.5 (s, 1H). 
Step-2A: Preparation of 2-(2-Indenyl)-7-methylindole: 
This compound was prepared by substantially the same procedure as Part IA, 
Step-2A. 
2-(2-Indenyl)-7-methylindole; yield 92%, mp 204.degree.-206.degree. C. The 
following NMR data were obtained: .sup.1 H NMR (CDCl.sub.3, 300 MHz): 
.delta. 2.6 (s, 3H), 3.85 (s, 2H), 6.7 (s, 1H), 7.0-7.5 (m, 8H), 8.2 (s, 
1H). 
Step-3A: Preparation of 
1-Methyl-12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-6H-5,7(5H,7H)-dione 
(Compound Ib-1) 
A mixture of 2-(2-indenyl)-7-methylindole (100 mg, 0.41 mmol) and maleimide 
(80 mg, 0.82 mmol) in a 10 cm sealed reaction vial was heated at 
180.degree.-185.degree. C. for 30 min. After cooling to ambient 
temperature, the product was dissolved in CH.sub.3 OH (5 mL) and 
precipitated by slow addition of ether-hexane (1:2) to yield a yellow 
amorphous solid. This solid, 
1-methyl-4c,7a,7b,12a-tetrahydro-6H,12H,13H-indeno[1,2-a]pyrrolo[3,4-c]car 
bazole-5,7(5H,7H)-dione, in toluene (20 mL) was added to solid 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (235 mg, 1.03 mmol) in one 
portion. The mixture was heated at 60.degree.-65.degree. C. for 6 hours. 
After cooling to ambient temperature, the solid precipitate was collected. 
The product was suspended and triturated in cold MeOH and the precipitate 
collected by filtration. The precipitate was washed with cold MeOH, and 
recrystallized from THF-MeOH-Et.sub.2 O to yield Compound Ib-1 as an 
orange powder. The yield was 35 mg (25% yield). The mp was greater than 
320.degree. C. The following NMR data were obtained: .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): .delta. 2.65 (s, 3H),-4.35 (s, 2H), 7.2 (t, 2H), 
7.35 (d, 1H), 7.4-7.55 (m, 2H), 7.8 (d, 1H), 8.8 (d, 1H), 9.15 (d, 1H), 
11.2 (s, 1H), 12.35 (s, 1H). MS(FAB): m/e 339 (m+1).sup.+. 
EXAMPLES V(F)(2) AND (3) 
Step-1A: Preparation of 2-(2-(2-Hydroxy)indanyl)-1-methylindole 
n-BuLi (6.1 mL of 2.5M solution in hexanes, 15.2 mmol) was added dropwise 
over a 10 min period to a solution of freshly distilled 1-methylindole 
(2.0 g, 15.2 mmol) in dry ether (15 mL) under a nitrogen atmosphere. The 
solution was stirred at reflux 6 hours. After cooling to ambient 
temperature, 2-indanone (2.2 g, 16.8 mmol) in ether (15 mL) was added 
dropwise. The mixture was stirred at reflux for 30 min, poured into 2N HCl 
(50 mL) and extracted with CH.sub.2 Cl.sub.2 (2.times.50 mL). The combined 
CH.sub.2 Cl.sub.2 layers were washed with H.sub.2 O (2.times.50 mL), 
saturated NaCl solution (2.times.50 mL) and dried (MgSO.sub.4). The 
product was purified by column chromatography (silica gel, CH.sub.2 
Cl.sub.2) to give 500 mg (13% yield) with an mp of 160.degree.-161.degree. 
C. The following NMR data were obtained: .sup.1 H NMR (CDCl.sub.3, 300 
MHz): .delta. 2.2 (s, 1H), 3.5 (d, 2H), 3.65 (d, 2H), 4.0 (s, 3H), 7.0-7.6 
(m, 9H). 
Step-2A: Preparation of 2-(2-Indenyl)-1-methylindole: 
This compound was prepared by substantially the same procedure as Part IA, 
Step-2A 
2-(2-Indenyl)-1-methylindole; yield 95%; mp 146.degree.-148.degree. C. The 
following NMR data were obtained: .sup.1 H NMR (CDCl.sub.3, 300 MHz): 
.delta. 4.0 (s, 2H), 4.1 (s, 3H), 7.1-7.7 (m, 10H). MS(FAB): m/e 245 
(m.sup.+). 
Step-3A: Preparation of 
13-Methyl-4c,7a7b,12a-tetrahydro-6H,12H-indeno[2,3-a]pyrrolo[3,4-c]carbazo 
le-5,7(5H,7H)-dione: 
A mixture of 2-(2-indenyl)-l-methylindole (300 mg, 1.4 mmol) and maleimide 
(200 mg, 2.1 mmol) in a 10 cm sealed reaction vial was heated at 
180.degree.-190.degree. C. for 30 min. After cooling to ambient 
temperature, MeOH (5 mL) was added and the crystals which formed were 
collected by filtration and washed with cold MeOH to give 335 mg (70% 
yield) of a light yellow solid product. The melting point was greater than 
220.degree. C. acetone-MeOH. The following NMR data were obtained: .sup.1 
H NMR (CDCl.sub.3, 300 MHz): .delta. 2.9 (m, 1H), 3.4-3.55 (m, 2H), 
3.65-3.95 (m, 5H), 4.5 (d, 2H), 7.1-7.5 (m, 7H), 8.1 (d, 1H). MS(FAB): m/e 
342(m.sup.+). 
EXAMPLE V(F)(4) 
Step-4A: Preparation of 
13-Methyl-6H,12H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)-dione 
(Compound I-4) 
Solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (500 mg, 2.2 mmol) was 
added in one portion to a solution of 
13-methyl-4c,7a,7b,12a-tetrahydro-6H,12H-indeno[2,3-a]pyrrolo[3,4-c]carbaz 
ole-5,7(5H,7H)-dione (300 mg, 0.9 mmol) in toluene (25 mL). The mixture was 
stirred at 60.degree.-65.degree. C. for 4 hours. After cooling in an 
ice-bath, the precipitate was collected by filtration. The solid was 
suspended in MeOH, recollected and washed with cold MeOH (5 mL). The 
product was recrystallized from THF-MeOH to give 260 mg (88% yield) of 
Compound I-4 as a yellowish powder. Compound I-4 has an mp of greater than 
220.degree. C. The following NMR data were obtained: .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): .delta. 4.2 (s, 3H), 4.6 (s, 2H), 7.3 (t, 1H), 
7.4-7.55 (m, 2H), 7.6 (t, 1H), 7.75 (m, 2H), 9.0 (d, 1H), 9.15 (d, 1H), 
11.2 (s, 1H). MS(FAB); m/e 338 (m.sup.+). 
EXAMPLE V(F)(5) 
(Method A) 
Preparation of a mixture of 
13-Methyl-6H,7H,12H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one and 
13-methyl-5H,6H,12H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-5) 
To a stirred suspension of Zn dust (800 mg) and mercuric chloride (100 mg) 
in water (5 mL) was added 0.5 mL of concentrated hydrochloric acid 
(dropwise). After 5 min, the aqueous layer was decanted. The zinc amalgam 
was first washed with water, then repeatedly washed with EtOH. The zinc 
amalgam was suspended in THF (40 mL), and solid Compound I-4 (Example 
V(A)(3)) (200 mg, 0.6 mmol) was added in one portion. HCl(g) was passed 
through while the solution was maintained at reflux for 1 hour. The 
reaction mixture was cooled on an ice bath, and a brown precipitate was 
collected by filtration and washed with MeOH (5 mL). Recrystallization 
from THF-ether gave 45 mg (23% yield) of the mixture as a tan powder 
product with amp of greater than 260.degree. C. The following NMR data 
were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 4.2 (s, 3H), 
4.6 (s, 1.67H), 4.75 (s, 0.33H), 4.85 (s, 0.33H), 4.90 (s, 1.67H), 
7.25-7.45 (m, 3H), 7.55 (t, 1H), 7.65 (d, 1H), 7.75 (d, 1H), 8.0 (d, 1H), 
8.55 (s, 0.83H), 8.8 (s, 0.17H), 9.3 (d, 0.17H), 9.5 (d, 0.83H). MS(FAB): 
m/e 325 (m+1).sup.+. 
G. Specific Description of Synthetic Processes 
Preparation of Methoxylated Fused Pyrrolocarbazoles 
Part VA: Methoxylated Derivatives 
EXAMPLE V(G)(1) 
Preparation of 5-Methoxy-2-(2-(2-hydroxy)indanyl)indole Step-1A: 
This compound was prepared by substantially the same procedure as Part IA, 
Step-1A except that 5-methoxyindole was substituted for I. 
5-Methoxy-2-(2-(2-hydroxy)indanyl)indole, yield 2.9 g (59%) mp 
139.degree.-142.degree. C. (ether-hexane). The following NMR data were 
obtained: .sup.1 H NMR (CDCl.sub.3) .delta. 2.3 (bs, 1H), 3.3 (d, 2H), 
3.55 (d, 2H), 3.9 (s, 3H), 6.35 (s, 1H), 6.8 (d, 1H), 7.05 (s, 1H), 
7.2-7.4 (m, 5H), 8.45 (bs, 1H). 
Step-2A: Preparation of 5-Methoxy,2-(2-indenyl)indole: 
This compound was prepared by substantially the same procedure as Part IA, 
Step-2A. 
5-Methoxy-2-(2-indenyl)indole; yield (59%) mp 208.degree.-210.degree. C. 
(ether-hexane) .sup.1 H NMR (CDCl3) .delta. 3.9 (s, 5H), 6.6 (s, 1H), 6.85 
(d, 1H), 7.05 (d, 2H), 7.15-7.3 (m, 3H), 7.4 (d, 1H), 7.45 (d, 1H), 8.15 
(bs, 1H). 
Step-3A: Preparation of 
6-Methoxy-4-cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro-[1H]indeno[2,3-a]9H- 
carbazole 
A mixture of 5-methoxy-2-(2-indenyl)indole (500 mg, 1.9 mmol) and ethyl 
cis-b-cyanoacrylate (5.0 g, 40 mmol), in a sealed reaction flask, was 
heated at 180.degree. C. with stirring for 1.5 hours. The mixture was 
cooled to ambient temperature, MeOH (10 mL) was added and the solution was 
cooled to -20.degree. C. The product was collected to give 175 mg (24%) of 
a light tan solid product, mp 278.degree.-282.degree. C. The following NMR 
data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 1.25 (t, 
3H), 3.1-3.35 (m, 3H), 3.8 (s, m, 4H), 3.9 (m, 1H), 4.3-4.55 (m, 2H), 4.6 
(d, 1H), 6.7 (d, 1H), 6.95 (s, 1H), 7.05-7.25 (m, 5H), 11.1 (s, 1H). IR 
(KBr) cm.sup.-1 : 2210 (CN); 1690 (C.dbd.O). 
Step-4A: Preparation of 
6-Methoxy-4-cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro-[1H]indeno[2,3-a]9H- 
carbazole. 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (185 mg, 0.81 mmol) was added in 
one portion to a stirred solution of 
6-methoxy-4-cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro-[1H]-indeno[2,3-a]9H 
-carbazole (125 mg, 0.32 mmol) in dry toluene (20 mL). The solution was 
stirred at 60.degree.-65.degree. C. for 6 hours. After cooling on an ice 
bath the precipitate was collected by filtration, the product was 
suspended in MeOH (20 mL), collected and washed with cold MeOH (10 mL). 
The filtrate was recrystallized from acetone to yield 110 mg (90%) of a 
light tan product. The melting point was greater than 250.degree. C. The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 1.4 (t, 3H), 3.9 (s, 3H), 4.25 (s, 2H), 4.6 (q, 2H), 7.25 (d, 1H), 
7.4 (m, 2H), 7.62 (m, 1H), 7.75 (m, 1H), 7.95 (d, 1H), 12.5 (s, 1H). IR 
(KBr) cm.sup.-1 : 2210 (CN); 1710 (C.dbd.O). MS(FAB): m/e 370 (m.sup.+). 
Step-5A: Preparation of 
3-Methoxy-5H,6H,12H,13H-Indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-13) 
A mixture of 
6-methoxy-4-cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro-[1H]indeno[2,3-a]9H- 
carbazole (80 mg, 0.21 mmol) and Raney Nickel catalyst (approx. 500 mg, wet 
form) in THF (50 mL) was hydrogenated at 35 psi on a Parr Apparatus for 12 
hours. THF (50 mL), was added and then the solvent was filtered through 
Celite.RTM. and concentrated at reduced pressure. The product was purified 
by column chromatography (silica gel, EtOAc:hexane, 2:1, R.sub.f =0.3) to 
yield 76 mg (94%) of Compound I-13 as an off white solid product. The 
melting point was greater than 300.degree. C. The following NMR data were 
obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 3.9 (s, 3H), 4.15 
(s, 2H), 4.95 (s, 2H), 7.1 (d, 1H), 7.3-7.8(m, 5H), 8.57 (s, 1H), 9.4(d, 
1H); 11.75 (s, 1H). MS(FAB): m/e 341 (m+1).sup.+. Anal. calc. for: 
C.sub.22 H.sub.16 N.sub.2 O.sub.2.0.75 H.sub.2 O; C, 74.66; H, 4.99; N, 
7.92. Found: C, 74.46; H, 4.65; N, 7.79. 
H. Specific Description of Synthetic Processes 
Preparation of Fused Pyrrolocarbazoles Having Expanded E Ring Derivatives 
Part VIA: Expanded E Ring Derivatives 
EXAMPLE V(H)(1) 
Step-1A: Preparation of 2-(2-(2-Hydroxy)-1,2,3,4-tetrahydronaphthyl)indole 
(FIG. 2, V, R.sup.2,R.sup.3 .dbd.H, X.dbd.CH.sub.2 CH.sub.2 
n-BuLi (85.3 mmol, 34 mL of 2.5M sol. in hexanes) was added dropwise to a 
solution of indole (10.0 g, 85.3 mmol) in dry THF (500 mL) at -78.degree. 
C. (nitrogen atmosphere) over a 15 min period. The solution was stirred 
for 30 min, followed by the addition (by bubbling) of CO.sub.2 (g) for 10 
min. The solution was allowed to warm to ambient temperature, then 
concentrated to approximately 300 mL at reduced pressure. THF (200 mL) was 
added and the solution was recooled to -78.degree. C. A solution of t-BuLi 
(85.3 mmol, 50 mL of 1.7M solution in hexanes) was then added dropwise. 
The resulting yellow solution was allowed to stir for 2 hours at 
-78.degree. C. Instead of 2-indanone, 2-tetralone (13.7 g, 12.9 mL, 93.7 
mmol) was added dropwise and the mixture was stirred for 1 hour. The 
reaction was quenched by addition of water (5 mL). The reaction was poured 
into a saturated NH.sub.4 Cl solution (250 mL), and extracted with ether 
(2.times.200 mL). The Et.sub.2 O layer was washed with 100 mL of a 
saturated NH.sub.4 Cl solution, followed by drying (MgSO.sub.4), and 
concentration to give an oil. The product was recrystallized from MeOH to 
give 10 g (45%) of a white solid product, (mp 191.degree.-192.degree. C.). 
The following NMR data was obtained: .sup.1 H NMR (CDCl.sub.3): d 2.1-2.2 
(b, 2H), 2.5-2.65 (m, 1H), 2.9-3.1 (m, 2H), 3.35 (m, 1H), 5.35 (s, 1H), 
6.2 (s, 1H), 6.2-7.1 (m, 6H), 7.35 (d, 1H), 7.4 (d, 1H), 11.5 (s, 1H). 
Anal. calc. for C.sub.18 H.sub.17 NO: C, 82.10; H; 6.51; N, 5.32. Found C, 
82.07; H, 6.47; N, 5.18. 
Step-2A: Preparation of 2-(2-(3,4-dihydro)naphthyl)indole 
To a stirred solution of 
2-(2-(2-Hydroxy)-1,2,3,4-(tetrahydronaphthyl)indole (step-1) (5.0 g, 19.0 
mmol) in acetone (150 mL) was added 2N HCl (5 mL) at ambient temperature. 
The solution was stirred for 1 hour, then water (approximately 25 mL) was 
added. The precipitate was collected by filtration, washed well with water 
and dried to give 4.5 g (97%) of purified product. A sample was 
recrystallized from MeOH to give product which exhibited mp of 
179.degree.-180.degree. C. The following NMR data were obtained: .sup.1 H 
NMR (CDCl.sub.3): .delta. 2.7 (m, 2H); 2.9 (m, 2H), 6.65 (s, 1H), 6.98 (t, 
1H), 7.05-7.15 (m, 6H), 7.35 (d, 1H), 7.5 (d, 1H), 11.35 (bs, 1H). Anal. 
calc. for C.sub.18 H.sub.15 N: C, 88.13; H, 6.16; N, 5.71. Found, C, 
88.24; H, 6.14; N, 5.61. 
Step-3A: Preparation of 
4c,7a,7b,12,13,13a-Hexahydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4,C]carbazole 
-5,7-(5H,7H)dione (FIG. 4, XVIII, A1, A2; B1, B2.dbd.O) 
A stirred mixture of 2-(2-(3,4-dihydronaphthyl)indole (500 mg, 2.0 mmol) 
and maleimide (300 mg, 3.1 mmol) in a sealed reaction vial was heated at 
180.degree.-190.degree. C. for 30 min. After cooling to ambient 
temperature, MeOH (5 mL) was added, the product was collected and 
recrystallized from MeOH to give 610 mg (89%) of a white solid product, mp 
256.degree.-258.degree. C. The following NMR data were obtained: .sup.1 H 
NMR (DMSO-d.sub.6, 300 MHz): .delta. 1.6-1.75 (m, 1H) 2.15 (d, 1H), 
2.9-3.0 (m, 2H), 3.15-3.25 (m, 1H), 3.45 (t, 1H), 3.95 (m, 1H), 4.3 (d, 
1H), 7.0-7.4 (m, 7H), 7.8 (d, 1H), 10.8 (s, 1H), 11.15 (s, 1H). 
Step-4: Preparation of 
12,13-Dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dion 
e (Compound I-14) 
Solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (930 mg, 4.1 mmol) was 
added in one portion to a solution of 
4c,7a,7b,12,13,13a-hexahydro-6H,14H-napthyl[3,4-a]pyrrolo[3,4-c]carbazole- 
5,7-(5H,7H)dione (400 mg, 1.2 mmol) in toluene (50 mL). The solution was 
maintained at 60.degree.-65.degree. C. for six hours. After cooling on an 
ice bath, the solid was collected by filtration, suspended in MeOH (20 mL) 
and the product collected by filtration to give 320 mg (79%) of Compound 
I-14 as an orange solid. The melting point was 258.degree.-260.degree. C. 
The following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 
MHz): .delta. 2.9 (m, 2H), 3.1 (m, 2H), 7.3-7.4 (m, 4H), 7.5-7.65 (m, 2H), 
8.15 (d, 1H), 8.95 (d, 1H), 11.1 (s, 1H), 12.0 (s, 1H). MS(FAB): m/e 338 
(m.sup.+). Anal. calc. for C.sub.22 H.sub.14 N.sub.2 O.sub.2 : C, 78.09; 
H, 4.17; N, 8.28. Found; C, 77.67; H, 3.96; N, 8.16. 
EXAMPLE V(H)(2) 
Preparation of 
6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)-dione (Compound 
I-15) 
Solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (465 mg, 2.1 mmol) was 
added in one portion to a solution of 
4c,7a,7b,12,13,13a-hexahydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole 
-5,7-(5H,7H)dione (200 mg, 0.59 mmol) in dry dioxane (30 mL). The solution 
was stirred at reflux for 12 hours. The mixture was cooled to ambient 
temperature, the precipate was removed by filtration, and the solvent 
concentrated at reduced pressure. The residue was heated to reflux in MeOH 
(25 mL), cooled to ambient temperature, recrystallized from THF-MeOH and 
the product collected to yield 120 mg (61%) of Compound I-15 as a brown 
solid. The melting point was greater than 330.degree. C. The following NMR 
data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 7.4 (t, 
1H), 7.6 (t, 1H); 7.7-7.8 (m, 3H), 8.1 (m, 1H), 8.2 (d, 1H), 8.6 (d, 1H), 
9.1 (d, 1H), 10.0 (m, 1H), 11.2 (s, 1H), 12.9 (s, 1H). MS(FAB): m/e 336 
(m.sup.+). Anal. calc. for C.sub.22 H.sub.12 N.sub.2 O.sub.2 : C, 78.56; 
H, 3.60; N, 8.33. Found; C, 78.03; H, 3.30; N, 8.12. 
EXAMPLE V(H)(3) 
Step-1B: Preparation of 
3-Cyano-4-ethoxycarbonyl-1,2,3,4-tetrahydro-1,2-dihydronaphthyl[3,4-a]9H-c 
arbazole and 
4-cyano-3-ethoxycarbonyl-1,2,3,4-tetrahydro-1,2-di-dronaphthyl[3,4-a]9H-ca 
rbazole 
A mixture of 2-(2-(3,4-dihydro)naphthyl)indole (FIG. 2, R.sup.2 R.sup.3, 
R.sup.4, R.sup.5 R.sup.6 .dbd.H, X.dbd.CH.sub.2 CH.sub.2 1.0 g, 4.1 mmol) 
and ethyl cis-.beta.-cyanoacrylate (5.0 g, 40 mmol) was heated in a sealed 
reaction flask at 180.degree. C. with stirring for 1 hour. The mixture was 
cooled to ambient temperature and the excess cyanoacrylate was removed by 
Kugelrohr distillation (oven temperature 80.degree.-85.degree. C., 0.5 
mm). MeOH (25mL) was added to the residue and the product triturated to 
give 700 mg (46%) of a white solid. The .sup.1 H NMR data showed 
approximately a 2:1 mixture of each of the 4-CN:3-CN isomers. The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 1.25 (t, 3H), 3.1-3.35 (m, 3H), 3.8 (s, m, 4H), 3.9 (m, 1H), 
4.3-4.55 (m, 2H), 4.6 (d, 1H), 6.7 (d, 1H), 6.95 (s, 1H), 7.05-7.25 (m, 
5H), 11.1 (s, 1H). 
Step-2B: Preparation of 
3-Cyano-4-ethoxycarbonyl-1,2-di-hydronaphthyl[3,4-a]9H-carbazole and 
4-cyano-3-ethoxycarbonyl-1,2-di-hydronaphthyl[3,4-a]9H-carbazole 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (900 mg, 4.0 mmol) was added in 
one portion to a stirred solution of the product from the preceding step 
(590 mg, 1.6 mmol) in dry toluene (50 mL). The solution was stirred at 
65.degree.-70.degree. C. for 6 hours. The mixture was cooled to ambient 
temperature and the precipitate removed by filtration, and washed with 
toluene (10 mL). The toluene solution was concentrated at reduced pressure 
to yield a crude solid. Purification by column chromatography (silica gel, 
EtOAc:Hexane 2:1) gave 510 mg (87%) of an off-white solid product. The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 1.15 and 1.4 (t, 3H), 2.9 and 3.1-3.2 (q, 2H), 4.35 and 4.6 (q, 
2H), 7.2-7.7 (m, 4H), 7.9 (d, 0.5H), 8.2 (d, 0.5H), 8.4 (d, 1H), 12.2 (d, 
1H). 
Step-3B: Preparation of 
12,13-dihydro-6H,7H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5(5H)one 
(Compound I-16) and 
12,13-Dihydro-5H,6H,14H-naphthy[3,4-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-17) 
The isomeric mixture from the preceding step (300 mg; 0.81 mmol) was added 
to Raney Nickel catalyst (approximately 1 g, wet form) in MeOH (75 mL)/THF 
(25 mL) and was hydrogenated at 35 psi on a Parr Apparatus for 12 hours. 
The solution was diluted with THF (50 mL), then filtered through 
Celite.RTM.. The solvent was concentrated at reduced pressure to give 210 
mg (80%) of crude product. The product was purified by column 
chromatography (silica gel; EtOAc:Hex; 2:1, R.sub.f 5-oxo=0.3 R.sub.f 
7-oxo=0.25). The fractions containing product were collected and 
concentrated to give a white solid. A sample was recrystallized from 
MeOH-ether and dried (100.degree. C., 0.5 mm, 12 hours) in order to obtain 
the following information: 
Compound I-16: 5-oxo isomer mp&gt;300.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 
300 MHz) .delta. 2.9 (m, 2H), 3.1 (m, 2H), 4.95 (s, 2H), 7.1 (t, 1H), 
7.3-7.48 (m, 4H), 7.55 (d, 1H), 7.85 (d, 1H), 8.75 (s, 1H), 9.15 (d, 1H), 
11.6 (s, 1H). MS(FAB): m/e=325 (M+1).sup.+. Anal. calc. for: C.sub.22 
H.sub.16 N.sub.2 O.0.1 H.sub.2 O; C, 81.01; H, 5.01; N, 8.59. Found: C, 
80.83; H, 5.04; N, 8.46. 
Compound I-17: 7-oxo isomer mp&gt;300.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 
300 MHz) .delta. 2.9 (m, 2H), 3.1 (m, 2H), 4.9 (s, 2H), 7.2-7.35 (t, 4H), 
7.5 (t, 1H), 7.6 (d, 1H), 8.0 (d, 1H), 8.2 (m, 1H), 8.4 (s, 1H), 11.7 (s, 
1H). MS(FAB): m/e=325 (M+1).sup.+. Anal. calc. for: C.sub.22 H.sub.16 
N.sub.2 O.0.25 H.sub.2 O; C, 80.34; H, 5.06; N, 8.52. Found: C, 80.16; H, 
5.08; N, 8.23. 
EXAMPLE V(H)(4) 
Preparation of 3-Bromo-12, 
13-dihydro-6H,7H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5(5H)one 
(Compound I-18) 
Solid N-bromosuccinimide (14 mg, 0.1 mmol) was added to a stirred solution 
of Compound I-16 (25 mg, 0.08 mmol) in dry THF (5 mL) under a nitrogen 
atmosphere. The solution was stirred at ambient temperature for 12 hours, 
then concentrated at reduced pressure. Recrystallization from MeOH gave 25 
mg (81%) of Compound I-18 as a white solid. The melting point was greater 
than 300.degree. C. (THF-MeOH). The following NMR data were obtained: 
.sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 2.9 (m, 2H), 3.2 (m, 2H), 
4.9 (s, 2H), 7.3-7.45 (m, 3H), 7.5-7.6 (m, 2H), 7.82 (d, 1H), 8.92 (s, 
1H), 9.35 (s, 1H), 11.8 (s, 1H). MS(FAB): m/e 403 (m.sup.+). 
EXAMPLE V(H)(5) 
Preparation of 
3-Bromo-12,13-Dihydro-5H,6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7(7 
H)one (Compound I-19) 
To a stirred solution of Compound I-17, (25 mg, 0.08 mmol) in dry THF (7 
mL) under a nitrogen atmosphere was added solid N-bromosuccinimide (14 mg, 
0.1 mmol). The solution was stirred at ambient temperature for 12 hours, 
then concentrated at reduced pressure. The product was recrystallized from 
MeOH-ether to yield 22 mg (71% yield) of Compound I-19 as a white solid. 
The melting point was greater than 300.degree. C. (THF-MeOH). The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 2.9 (m, 2H), 3.05 (m, 2H), 4.95 (s, 2H), 7.3-7.35 (m, 3H), 
7.55-7.65 (m, 2H), 8.15 (s, 1H), 8.2 (m, 1H), 8.48 (s, 1H), 11.9 (s, 1H). 
MS(FAB): m/e 403 (m.sup.+). 
EXAMPLE V(H)(6) 
Step-1: Preparation of 
5-fluoro-2-(2-(2-hydroxy)-1,2,3,4-tetrahydronaphthyl)indole (FIG. 3, V, 
R.sup.2 .dbd.H, R.sup.3 .dbd.F on C5, X.dbd.CH.sub.2 CH.sub.2) 
Preparation of this compound used substantially the same procedure as 
Example V(H)(1), Step-1A, except that 5-fluoroindole (3.35 g, 24.8 mmol) 
and 2-tetralone (4.0 g, 27.3 mmol) were used to give 
5-fluoro-2-(2-(2-hydroxy)-1,2,3,4-tetrahydronaphthyl)indole; yield 1.8 g 
(26%), mp 158.degree.-159.degree. C. dec (ether-hexane). The following NMR 
data were obtained: .sup.1 H NMR (CDCl.sub.3, 300 MHz): d 2.1 (s, 1H), 
2.25 (t, 2H), 2.8-2.9 (m, 1H), 3.05-3.2 (m, 2H), 3.45 (d, 1H), 6.23 (s, 
1H), 6.9 (t, 1H), 7.1-7.3 (m, 6H), 8.55 (bs, 1H). 
Step-2: Preparation of 2-(2-(3,4-dihydro)naphthyl)-5-fluoroindole 
Substantially the same procedure as Example V(H)(1), Step-2A was employed 
using 5-fluoro-2-(2-(2-hydroxy)-1,2,3,4-tetrahydronaphthyl)indole (1.0 g, 
3.6 mmol); yield 900 mg (96%), mp 174.degree.-176.degree. C. dec 
(MeOH-ether). The following NMR data were obtained: .sup.1 H NMR 
(CDCl.sub.3, 300 MHz): .delta. 2.75-2.82 (m, 2H), 2.95-3.02 (m, 2H),6.65 
(s, 1H), 6.8 (s, 1H), 6.9-7.0 (m, 1H), 7.1-7.3 (m, H), 8.25 (bs, 1H). 
Step-3: Preparation of 
3-Cyano-4-ethoxycarbonyl-6-fluoro-1,2,3,4-tetrahydro-1,2-dihydronaphthyl[3 
,4-a]-9H-carbazole and 
4-cyano-3-ethoxycarbonyl-6-fluoro-1,2,3,4-tetrahydro-1,2-dihydronaphthyl[3 
,4-a]-9H-carbazole (FIG. 3 XII and XV, R.sup.2, R.sup.3, R.sup.5, R.sup.6 
.dbd.H, R.sup.4 .dbd.F) (X.dbd.CH.sub.2 CH.sub.2) 
A mixture of 2-(2-(3,4-dihydro)naphthyl)-5-fluoroindole (700 mg, 2.7 mmol) 
and ethyl cis-.beta.-cyanoacrylate (3.3 g, 27 mmol) was heated in a sealed 
reaction flask at 180.degree. C. with stirring for 1 hour. The mixture was 
cooled to ambient temperature and the excess cyanoacrylate was removed by 
Kugelrohr distillation (oven temperature 80.degree.-85.degree. C., 0.5 
mm). MeOH (25 mL) was added to the residue and the 4-cyano product was 
separated to give 400 mg (39%) of a white solid, mp 
256.degree.-258.degree. C. The following NMR data were obtained: .sup.1 H 
NMR (DMSO-d.sub.6, 300 MHz): .delta. 1.25 (t, 3H), 3.1-3.35 (m, 3H), 3.8 
(s, m, 4H), 3.9 (m, 1H), 4.3-4.55 (m, 2H), 4.6 (d, 1H), 6.7 (d, 1H), 6.95 
(s, 1H), 7.05-7.25 (m, 5H), 11.1 (s, 1H). 
Step-4: Preparation of 
3-Cyano-4-ethoxycarbonyl-6-fluoro-1,2-tetrahydronaphthyl[3,4-a]9H-carbazol 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (475 mg, 2.1 mmol) was added in 
one portion to a stirred solution of 
3-cyano-4-ethoxycarbonyl-6-fluoro-1,2,3,4-tetrahydro-1,2-dihydronaphthyl[3 
,4-a]9H-carbazole (325 mg, 0.84 mmol) in dry toluene (50 mL). The solution 
was stirred at 65.degree.-70.degree. C. for 6 hours. The mixture was 
cooled to ambient temperature, the precipitate removed by filtration, and 
washed with toluene (10 mL). The toluene solution was concentrated at 
reduced pressure to give a crude solid. Purification of the combined solid 
by column chromatography (silica gel, EtOAc:Hexane 2:1) gave 275 mg (85%) 
of a light yellow solid product, mp 258.degree.-260.degree. C. The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 1.2 (t, 3H), 2.9-3.0 (q, 2H), 3.1-3.2 (m, 2H), 4.35 (q, 2H), 
7.3-7.5 (m, 5H), 7.7 (m, 1H), 8.1 (m, 1H), 12.25 (s, 1H). 
Step-5: Preparation of 
12,13-Dihydro-3-fluoro-5H,6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7( 
7H)one (Compound I-22) 
A solution of 
3-cyano-4-ethoxycarbonyl-6-fluoro-1,2-tetrahydronaphthyl[3,4-a]9H-carbazol 
e (140 mg; 0.37 mmol) and Raney Nickel catalyst (approximately 0.5 g, wet 
form) in MeOH (40 mL)/THF (20 mL) was hydrogenated at 35 psi on a Parr 
Apparatus for 12 hours. The solution was diluted with THF (50 mL), then 
filtered through Celite.RTM.. The solvent was concentrated at reduced 
pressure and the product was recrystallized to give 35 mg (28%) of a white 
solid (Compound I-22). The melting point was greater than 300.degree. C. 
The following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz) 
.delta. 2.85 (m, 2H), 3.02 (m, 2H), 4.9 (s, 2H), 7.2-7.35 (m, 4H), 7.6 (m, 
1H), 7.8 (d, 1H), 8.2 (m, 1H), 8.45 (m, 1H), 11.95 (bs, 1H). MS(FAB): 
m/e=343 (M+1).sup.+. 
EXAMPLE V(H)(7) 
Step-1: Preparation of 
2(2-(2-Hydroxy-6-fluoro-1,2,3,4-tetrahydronaphthyl))indole 
This compound was prepared by substantially the same procedure as Example 
V(H)(1), step-1A, except that 6-fluoro-2-tetralone and indole were used to 
give 2-(2-(6-fluoro-2-hydroxy-1,2,3,4-tetrahydronephthyl)indole; mp 
187.degree.-188.degree. C. .sup.1 H NMR (CDCl.sub.3, 300 MHz): d 2.05 (s, 
1H), 2.25 (m, 2H), 2.75-2.9 (m, 1H), 3.0-3.15 (m, 2H), 3.4 (m, 2H), 6.25 
(s, 1H), 7.0-7.2 (m, 3H), 7.25-7.35 (m, 2H), 7.4 (d, 1H), 7.55 (d, 1H), 
8.55 (s, 1H). Anal. calc. for C.sub.18 H.sub.16 BrNO: C, 63.17; H, 4.71; 
N, 4.09; Br, 23.35. Found; C, 63.06; H, 4.71; N, 4.02; Br, 23.57. 
Step-2: Preparation of 2-(2-(6-Fluoro-3,4-dihydronaphthyl)indole) 
Substantially the same procedure as Example V(H)(1), step-2A, was employed 
using 2-(2-(2-hydroxy-6-fluoro-1,2,3,4-tetrahydronaphthyl)indole) (Step-1) 
to give the subject compound, mp 228.degree.-231.degree. C. .sup.1 H NMR 
(CDCl.sub.3, 300 MHz): d 2.8 (m, 2H), 2.95 (m, 2H), 6.70 (s, 1H), 6.75 (s, 
1H), 7.0 (m, 2H), 7.1 (m, 1H), 7.2-7.4 (m, 4H), 7.4 (d, 1H), 7.6 (d, 1H), 
8.3 (s, 1H). Anal. calc. for C.sub.18 H.sub.14 BrN: C, 66.58; H, 4.33; N, 
4.22; F, 24.87. Found; C, 66.68; H, 4.35; N, 4.32; F, 24.64. 
Step-3: preparation of 
10-Fluoro-4c,7a,7b,12,13,13a-hexahydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c 
]carbazole-5,7-(5H,7H)dione 
A stirred mixture of 2-(2-(6-fluoro-3,4-dihydronaphthyl)indole (500 mg, 1.9 
mmol) and maleimide (370 mg, 3.8 mmol) in a sealed reaction vial was 
heated at 180.degree.-190.degree. C. for 2 h. After cooling to ambient 
temperature, MeOH (3 mL) was added and the product was collected and 
recrystallized from MeOH to give 465 mg (68%) of a white solid, mp 
322.degree.-325.degree. C. .sup.1 H NMR (acetone-d.sub.6, 300 MHz): d 
2.76-2.84 (m, 1H), 2.98-3.10 (m, 1H), 3.17-3.20 (m, 1H), 3.95-3.96 (m, 
2H), 4.24-4.32 (m, 1H), 4.53 (t, 1H, J=5.8 Hz), 4.93-4.98 (dd, 1H, J=6 Hz, 
1.8 Hz), 5.34-5.37 (dd, 1H, J=6.8 Hz, 1.8 Hz), 7.85-7.92 (m, 2H), 
7.97-8.09 (m, 3H), 8.30 (d, 1H, J=7.5 Hz), 8.38-8.43 (m, 1H), 8.94 (d, 1H, 
J=8.1 Hz), MS(m/e)=360 (m.sup.+). 
Step-4: preparation of 
10-Fluoro-12,13-dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5,7( 
5H,7H)dione (Compound Ia-4) 
To a solution of 
10-fluoro-4c,7a,7b,12,13,13a-hexahydro-6H,14H-napthyl[3,4-a]pyrrolo[3,4-c] 
carbazole-5,7-(5H,7H)dione (400 mg, 1.1 mmol) in toluene (50 mL) was added 
solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (630 mg, 2.8 mmol) in one 
portion. The solution was maintained at 60.degree.-65.degree. C. for six 
hours. After cooling on an ice bath, the solids were collected by 
filtration, suspended in MeOH (25 mL) and the product collected by 
filtration to give 30 mg (77%) of Compound Ia-4, mp 
304.degree.-305.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 
2.91-2.96 (m, 2H), 3.1-3.35 (m, 2H), 7.11-7.18 (m, 1H), 7.24-7.34 (m, 2H), 
7.54-7.63 (m, 2H), 8.20 (t, 1H, J=6.5 Hz), 8.94 (d, 1H, J=7.9 Hz), 11.14 
(s, 1H), 12.0 (s, 1H). MS (m/e)=325 (m+1).sup.+. Anal. calc. for C.sub.22 
H.sub.13 N.sub.2 O.sub.2 F: C, 74.15; H, 3.68;N, 7.86. Found; C, 73.79; H, 
3.50; N, 7.71. 
EXAMPLE V(H)(8) 
Step-1: Preparation of 
2-(2-(2-Hydroxy-6-bromo-1,2,3,4-tetrahydro)naphthyl)indole 
The subject compound was prepared by substantially the same procedure as 
Example V(H)(1), step-1A, except that 6-bromo-2-tetralone and indole were 
used to give 2-(2-(2-hydroxy-6-bromo-1,2,3,4-tetrahydro)naphthyl)indole; 
mp 231.degree.-232.degree. C. .sup.1 H NMR (CDCl.sub.3, 300 MHz): d 2.1 
(s, 1H), 2.3 (m, 2H), 2.8-2.9 (m, 1H), 3.0-3.15 (m, 2H), 3.4 (m, 2H), 6.25 
(s, 1H), 6.8-6.9 (m, 2H), 7.05-7.20 (m, 3H), 7.4 (d, 1H), 7.55 (d, 1H), 
8.55 (s, 1H). Anal. calc. for C.sub.18 H.sub.16 FNO: C, 76.85; H, 5.93; N, 
4.98; F, 6.75. Found; C, 76.36; H, 5.75; N, 4.99; F, 6.66. 
Step-2: Preparation of 2-(2-(6-bromo-3,4-dihydro)naphthyl)indole 
Substantially the same procedure as Example V(H)(1), step-2A, was employed 
using 2-(2-(2-Hydroxy-6-bromo-1,2,3,4-tetrahydro)naphthyl)indole (Step-1) 
to give the subject compound, mp 193.degree.-195.degree. C. .sup.1 H NMR 
(CDCl.sub.3, 300 MHz): d 2.8 (m, 2H), 2.95 (m, 2H), 6.65 (s, 1H), 6.75 (s, 
1H), 6.9 (m, 2H), 7.1 (m, 2H), 7.2 (t, 1H), 7.4 (d, 1H), 7.6 (d, 1H), 8.3 
(s, 1H). Anal. calc. for C.sub.18 H.sub.14 FN: C, 82.11; H, 5.36; N, 5.32; 
F, 7.22. Found; C, 81.94; H, 5.34; N, 5.30; F, 7.24. 
Step-3: Preparation of 
10-Bromo-4c,7a,7b,12,13,13a-hexahydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c] 
carbazole-5,7-(5H,7H)dione 
A stirred mixture of 2-(2-(6-bromo-3,4-dihydro)naphthyl)indole (400 mg, 
0.95 mmol) and maleimide (540 mg, 2.4 mmol) in a sealed reaction vial was 
heated at 190.degree. C. for 2 h. After cooling to ambient temperature, 
MeOH (3 mL) was added and the product was collected and recrystallized 
from MeOH to give 500 mg (77%) of the subject compound as a yellow solid, 
mp&gt;320.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 1.61 (m, 1H), 
2.10 (m, 1H), 2.91-2.93 (m, 2H), 3.17-3.30 (m, 2H), 3.91-3.95 (m, 1H), 
4.24 (d, 1H, J=7.7 Hz), 6.97-7.09 (m, 2H), 7.28-7.37 (m, 4H), 7.82 (d, 1H, 
J=7.8 Hz), 10.86 (s, 1H), 11.14 (s, 1H); MS(m/e)=422 (m+1).sup.+. 
Step-4: Preparation of 
10-Bromo-12,13-dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]-carbazole-5,7( 
5H,7H)dione (Compound Ia-5) 
To a solution of 10-bromo-4c,7a,7b,12,13,13a-hexahydro-6H, 
14H-naphhyl[3,4-a]pyrrolo[3,4-c]carbazole-5,7-(5H,7H)dione (400 mg, 0.95 
mmol) in toluene (50 mL) was added solid 
2,3-dichloro-5,6-dicyano-1,4-benzoquinone (540 mg, 2.4 mmol) in one 
portion. The solution was maintained at 60.degree.-65.degree. C. for six 
hours. After cooling on an ice bath, the solids were collected by 
filtration, suspended in MeOH (25 mL) and the product was collected by 
filtration to give 365 mg (92%) of Compound Ia-5, mp&gt;300.degree. C. .sup.1 
H NMR (DMSO-d.sub.6, 300 MHz): d 2.91-2.96 (m, 2H), 3.09-3.12 (m, 2H), 
7.25-7.33 (m, 2H), 7.50-7.63 (m, 3H), 8.09 (d, 1H, J=8.5 Hz), 8.93 (d, 1H, 
J=7.9 Hz), 11.16 (s, 1H), 12.06 (s, 1H). MS (m/e)=418 (m+1).sup.+. 
EXAMPLE V(H)(9) 
Preparation of 
10-(2-(4-Pyridylethenyl)-12,13-dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4c] 
-carbazole-5,7(5H,7H)dione (Compound Ia-6) 
To a solution of 
10-Bromo-12,13-Dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5,7(5 
H,7H)dione (Compound Ia-5) (120 mg, 0.29 mmol), 2-vinylpyridine (60 mg, 
0.58 mmol) and triethylamine (0.5 mL) in DMF (4 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (20 mg). The solution was heated 
in a sealed reaction tube at 100.degree.-110.degree. C. for 48 h. The 
mixture was cooled to ambient temperature, filtered through a pad of 
diatomaceous earth (Celite.RTM.), and the solvent was concentrated at 
reduced pressure. The product was triturated with MeOH to give 125 mg 
(99%) of a yellow solid. Recrystallization from MeOH-Et.sub.2 O gave 
Compound Ia-6 as a yellow solid, mp&gt;320.degree. C. .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): d 2.97-3.00 (m, 2H), 3.13-3.17 (m, 2H), 7.29-7.41 
(m, 3H), 7.57-7.63 (m, 3H), 7.70 (d, 1H, J=7.7 Hz), 7.77-7.83 (m, 2H), 
8.18 d, 1H, J=8.3 Hz), 8.61 (s, 1H), 8.95 (d, 1H, J=7.9 Hz), 11.14 (s, 
1H), 12.04 (s, 1H). MS(FAB): m/e 442 (m+1).sup.+. 
EXAMPLE V(H)(10) 
Preparation of 
10-(2-(4-Pyridylethyl))-12,13-dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4c]- 
carbazole-5,7(5H,7H)dione (Compound Ia-7) 
To 
10-(2-(4-Pyridylethenyl))-12,13-Dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4- 
c]-carbazole-5,7(5H,7H)dione (Compound Ia-6) (100 mg, 0.23 mmol) in DMF (30 
mL) was added a small spatula of raney nickel catalyst. The solution was 
hydrogenated at 40 psi for 12 h. The solvent was filtered through a pad of 
Celite.RTM., and then concentrated at reduced pressure. The product was 
recrystallized from MeOH to give 90 mg (90%) of Compound Ia-7 as a light 
yellow solid, mp&gt;320.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 
2.93-2.97 (m, 2H), 3.00-3.15 (m, 6H), 7.18-7.34 (m, 5H), 7.54-7.59 (m, 
3H), 8.07 (d, 1H, J=8.0), 8.55 (m, 1H), 9.40 (d, 1H, J=7.8 Hz), 11.05 (bs, 
1H), 11.98 (s, 1H). MS(FAB): m/e 444 (m+1).sup.+. 
EXAMPLE V(H)(11) 
Preparation of 
5-Hydroxy-12,13-dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7(7H 
)one (Compound I-38) 
To a solution of 
12,13-dihydro-6H,14H-naphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dion 
e (Compound I-15) (25 mg, 0.07 mmol) in DMF (5 mL) was added NaBH.sub.4 (50 
mg). The mixture was stirred 12 h at ambient temperature, and then 
concentrated at reduced pressure. The product was recrystallized from 
DMF-MeOH-Et.sub.2 O to give 20 mg (80%) of Compound I-38 as a yellow 
solid, mp&gt;320.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 6.5 (bs, 
1H), 6.86 (s, 1H), 7.3 (t, 1H), 7.56 (t, 1H), 7.65-7.8 (m, 3H), 8.1 (d, 
1H), 8.19 (d, 1H), 8.65 (d, 1H), 9.2-9.3 (m, H), 12.45 (s, 1H). MS m/e=337 
(m-1).sup.+. 
I. Specific Description of Synthetic Processes 
Preparation of Benzothienyl Fused Pyrrolocarbazoles 
Part VII: Benzothienyl Derivatives 
EXAMPLE V(I)(1) 
Preparation of 
6H,12-Benzo[b]thieno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione 
(Compound I-20) 
A solution of 2-(2-benzo[b]thienyl)indole (FIG. 2, V R, R.sup.2, R.sup.3 
.dbd.H, X.dbd.S, 250 mg, 1.0 mmol), maleimide (120 mg, 1.2 mmol) and 
trifluoroacetic acid (1 mL) in dry toluene (75 mL) was stirred at reflux 
for 12 hours. The solution was cooled to ambient temperature and 
concentrated at reduced pressure to yield a crude solid. The solid was 
dissolved in glacial HOAc (40 mL), 5% Pd(OAc).sub.2 was added and the 
mixture maintained at reflux for 12 hours. The solution was cooled to 
ambient temperature, filtered through Celite.RTM., then concentrated at 
reduced pressure. MeOH was added to the residue and the product collected 
(80 mg, 23%). The product was further purified by column chromatography 
(EtOAc:Hexane 2:1 R.sub.f =0.5) to give Compound I-20. The melting point 
was greater than 300.degree. C. The following NMR data were obtained: 
.sup.1 H NMR (DMSO-d.sub.6, 300 MHz) .delta. 7.4 (t, 1H), 7.55-7.75 (m, 
4H), 8.25 (m, 1H), 9.05 (d, 1H), 9.8 (m, 1H), 11.4 (s, 1H), 12.8 (s, 1H). 
MS(FAB): m/e=343 (M+1).sup.+. Anal. calc. for: C.sub.20 H.sub.10 N.sub.2 
OS.0.5 H.sub.2 O; C, 67.49; H, 3.26; N, 7.87. Found: C, 67.50; H, 3.07; N, 
7.51. 
EXAMPLES V(I)(2) AND V(I)(3) 
Preparation of 
6H,7H,12H-Benzo[b]thieno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)one and 
6H,7H,12H-Benzo[b]thieno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one (Compounds 
I-42 and I-43) 
To a stirred suspension of Zn dust (500 mg) and mercuric chloride (150 mg) 
in water (3 mL) was added dropwise 0.5 mL of concentrated hydrochloric 
acid. After 10 minutes, the aqueous layer was decanted. The zinc amalgam 
was first washed with water, then repeatedly with EtOH. The zinc amalgam 
was suspended in EtOH (10 mL) and solid 
6H,12-Benzo[b]thieno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione 
(Compound I-20) (40 mg, 0.12 mmol) was added. A few drops of concentrated 
hydrochloric acid was added and then the reaction was brought to reflux. 
After 3 hours the reaction was allowed to cool to ambient temperature and 
the solvent was removed at reduced pressure. The residue was dissolved in 
THF-EtOAc (1:1, 50 mL) and extracted with saturated NaCO.sub.3 solution 
(2.times.25 mL), saturated NaCl solution (2.times.25 mL), and dried 
(MgSO.sub.4). After filtration the solvent was removed at reduced pressure 
to give a yellow solid. The product was first purified by column 
chromotography (silica gel, 2:1 EtOAc/hexanes) to give a mixture of 
regioisomers of 2:1 (7-oxo/5-oxo). The 5- and 7-oxo isomers were separated 
by reverse-phase HPLC to give 24 mg of the 7-oxo and 12 mg of the 5-oxo 
isomers (total yield 89%). The following data were obtained: 5-oxo isomer 
(Compound I-42), mp&gt;300.degree. C., .sup.1 H NMR (DMSO-d.sub.6, 300 MHz); 
d 5.10 (s, 2H), 7.26 (t, 1H, J=8.1 Hz), 7.39 (dt, 1H, J=6.9, 1.5 Hz), 7.47 
(t, 1H, J=7.3 Hz), 7.61 (dt, 2H, J=6.9, 1.5 Hz), 8.21 (dt, 2H, J=7.3, 5.1 
Hz), 8.89(s, 1H), 9.23 (d, 1H, J=8.1Hz), 12.31 (s, 1H). MS (ID): m/e 
329.17 (m+1). 7-oxo isomer (Compound I-43), mp&gt;300.degree. C. .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz); d 5.01 (s, 2H), 7.29 (t, 1H, J=7.3 Hz), 7.35 (m, 
1H), 7.53 (m, 1H), 7.68 (t, 2H, J=8.8 Hz), 8.14 (dd, 2H, J=8.8, 5.6 Hz), 
8.74 (s, 1H), 10.24 (m, 1H), 12.43 (s, 1H). MS (ID): m/e 329.18 (m+1). 
J. Specific Description of Synthetic Processes 
Preparation of Benzofuranyl Fused Pyrrolocarbazoles 
Part VIII: Benzofuranyl Derivatives 
EXAMPLE V(J)(1) 
Preparation of 
6H,13H-Benzofuranyl[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione 
(Compound I-21) 
This compound was prepared from 2-(2-benzofuranyl)indole (FIG. 2, VI, R, 
R.sup.2, R.sup.3 .dbd.H; X.dbd.O) and maleimide by substantially the same 
procedure as in Part VII to give Compound I-21. The melting point was 
greater than 300.degree. C. The following NMR data were obtained: .sup.1 H 
NMR (DMSO-d.sub.6, 300 MHz) .delta. 7.3 (t, 1H, 7.5-7.7 (m, 4H), 7.9 (d, 
1H), 8.7 (m, 1H), 8.9(m, 1H), 11.2(b, 1H), 12.8 (b, 1H). MS(FAB): m/e326 
(M.sup.+). 
K. Specific Description of Synthetic Processes 
Preparation of Aryl, Alkyl, Alkynyl and Substituted Alkyl and Alkanyl Fused 
Pyrrolocarbazoles 
Part IX: Aryl, Arylalkenyl and Heteroarylalkenyl Derivatives 
EXAMPLE V(K)(1) 
Preparation of 
3-Phenyl-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-27) 
A solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (100 mg, 0.26 mmol), phenylboronic acid (35 mg, 0.29 mmol) 
and bis(triphenylphosphine)palladium(II) chloride (25 mg) in DMF (5 ml) 
was heated in a sealed reaction tube at 100.degree.-110.degree. C. for 24 
hours. The mixture was cooled to ambient temperature, filtered through a 
pad of Celite.RTM. and concentrated at reduced pressure. The product was 
triturated with THF to give 77 mg of a brown solid which contained product 
and starting material. HPLC purification gave Compound I-27 as a tan 
solid. The melting point was greater than 300.degree. C. The following NMR 
data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 4.2 (s, 
2H), 5.05 (s, 2H), 7.3-7.55 (m, 5H), 7.7 (d, 2H, J=8 Hz), 7.8-7.9 (m, 3H), 
8.2 (s, 1H); 8.6 (s, 1H), 9.4 (d, 1H, J=9 Hz), 12.0 (s, 1H). MS(FAB): m/e 
387 (m+1).sup.+. 
EXAMPLE V(K)(2) 
Preparation of 
3-(2-Phenylethenyl)-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7 
H)-one (Compound I-24) 
To a solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (100 mg, 0.26 mmol), styrene (30 mg, 0.29 mmol) and 
triethylamine (0.5 mL) in DMF (4 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (25 mg). The solution was heated 
in a sealed reaction tube at 100.degree.-110.degree. C. for 48 hours. The 
mixture was cooled to ambient temperature, filtered through a pad of 
Celite.RTM., then the solvent was concentrated at reduced pressure. The 
product was triturated with MeOH to give 85 mg (80%) of a brown solid. 
Recrystallization from DMF-Et.sub.2 O gave the product, Compound I-24, as 
a tan solid. The melting point was greater than 300.degree. C. The 
following NMR data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 4.2 (s, 2H), 5.02 (s, 2H), 7.25-7.5 (m, 7H), 7.6-7.75 (m,4H), 7.8 
(d, 1H, J=8Hz), 8.2 (s, 1H), 8.6 (s, 1H), 9.4 (d, 1H, J=9 Hz), 12.8 (s, 
1H). MS(FAB): m/e 413 (m+1).sup.+. 
EXAMPLE V(K)(3) 
3-(2-Pyridinylethenyl)-5H,6H,12H,13H-indeno[2,3-a 
]pyrrolo[3,4-c]carbazole-7(7H)-one (Compound I-32). 
To a solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (100 mg, 0.26 mmol), 2-vinylpyridine (54 mg, 0.6 mL, 0.51 
mmol) and triethylamine (0.5 mL) in DMF (4 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (30 mg). The solution was heated 
in a sealed reaction tube at 100.degree.-110.degree. C. for 48 h. The 
mixture was cooled to ambient temperature, filtered through a pad of 
Celite.RTM., then the solvent was concentrated at reduced pressure. The 
product was triturated with MeOH to give 90 mg (84%) of Compound I-31 as a 
yellow solid, purification by column chromatography (silica gel, 
EtOAc:MeOH, 9:1), mp&gt;320.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): 
.delta. 4.2 (s, 2H), 5.0 (s, 2H), 7.2-7.42 (m, 4H), 7.58-7.7 (m, 4H), 
7.8-7.95 (m, 2H), 8.3 (s, 1H), 8.6 (d, 1H, J=6 Hz), 8.63 (s, 1H), 9.4 (d, 
1H, J=9 Hz), 12.1 (s, 1H). MS(FAB): m/e 414 (m+1).sup.+. 
Part X: Ester Derivatives 
EXAMPLE V(K)4 
Preparation of 3-(3-Ethyl 
propenoate)-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-25). 
To a solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (100 mg, 0.26 mmol), ethyl acrylate (52 mg, 0.05 mL, 0.52 
mmol) and triethylamine (0.5 mL) in DMF (4 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (25 mg). The solution was heated 
in a sealed reaction tube at 100.degree.-110.degree. C. for 48 h. The 
mixture was cooled to ambient temperature, filtered through a pad of 
Celite.RTM., and concentrated at reduced pressure. The product was 
triturated with MeOH to a solid, and it was recrystallized from THF-MeOH 
to give 75 mg (72%) of Compound I-25 as a tan solid. The melting point was 
greater than 300.degree. C. The following NMR data were obtained: .sup.1 H 
NMR (DMSO-d.sub.6, 300 MHz): .delta. 1.3 (t, 3H, J=6 Hz), 4.2-4.3 (s, m, 
4H), 5.0 (s, 2H), 6.75 (d, 1H, J=20 Hz), 7.35-7.75 (m, 2H), 7.85-7.95 (m, 
2H), 8.4 (s, 1H), 8.65 (m, 1H), 9.4 (d, 1H, 8 Hz), 12.2 (s, 1H). MS(FAB): 
m/e 409 (m+1).sup.+. 
EXAMPLE V(K)(5) 
Preparation of 
3-(2-(4-Pyridyl)ethenyl)-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazol 
e-7(7H)-one (Compound I-33) 
To a solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (100 mg, 0.26 mmol), 4-vinylpyridine (55 mg, 0.52 mmol) and 
triethylamine (0.5 mL) in DMF (4 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (30 mg). The solution was heated 
in a sealed reaction tube at 100.degree.-110.degree. C. for 48 h. The 
mixture was cooled to ambient temperature, filtered through a pad of 
Celite.RTM., and the solvent was concentrated at reduced pressure. The 
product was triturated with MeOH to give 75 mg (70%) of a tan solid. 
Recrystallization from DMF-THF-Et.sub.2 O gave Compound I-33 as a tan 
solid, mp&gt;330.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 4.19 (s, 
2H), 5.02 (s, 2H), 7.30-7.43 (m, 3H), 7.59-7.85 (m,6H), 8.28 (s, 1H), 8.55 
(bs, 2H), 8.65 (s, 1H), 9.41 (d, 1H, J=7.3 Hz), 12.10 (s, 1H). MS m/e=414 
(m+1).sup.+. Anal. calc. for C.sub.28 H.sub.19 N.sub.3 O.2.5 H.sub.2 O: C, 
73.35; H, 5.28; N, 9.16. Found; C, 73.66; H, 4.92; N, 8.82. 
EXAMPLE V(K)(6) 
Preparation of 
3-(2-(2-Phthalimido)ethenyl)-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carb 
azole-7(7H)-one (Compound I-39) 
To a solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (150 mg, 0.39 mmol), N-vinylphthalimide (134 mg, 0.77 mmol) 
and triethylamine (0.5 mL) in DMF (4 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (25 mg). The solution was heated 
in a sealed reaction tube at 100.degree.-110.degree. C. for 48 h. The 
mixture was cooled to ambient temperature, filtered through a pad of 
Celite.RTM., and the solvent was concentrated at reduced pressure. The 
product was triturated with MeOH to give 85 mg (80%) of a brown solid. 
Recrystallization from DMF-Et.sub.2 O gave Compound I-39 as a tan solid, 
mp&gt;300.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 4.17 (s, 2H), 
5.03 (s, 2H), 7.35-7.42 (m, 4H), 7.60-7.72 (m, 4H), 7.87-7.97 (m, 3H), 
8.10 (s, 1H), 8.61 (s, 1H), 9.40 (d, 1H, J=7.2 Hz), 12.03 (s, 1H). MS 
m/e=504.5 (m+23(Na)).sup.+. 
EXAMPLE V(K)(7) 
Preparation of 
3-(2-(2-Pyridylethenyl))-6H,7H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazol 
e-5(5H)-one (Compound I-41) 
To a solution of 
3-bromo-6H,7H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5)one 
(Compound I-8) (450 mg, 1.16 mmol), 2-vinylpyridine (245 mg, 2.3 mmol) and 
triethylamine (0.5 mL) in DMF (6 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (25 mg). The solution was heated 
in a sealed reaction tube at 100.degree.-110.degree. C. for 48 h. The 
mixture was cooled to ambient temperature, filtered through a pad of 
Celite.RTM., and the solvent was concentrated at reduced pressure. The 
product was triturated with MeOH to give 300 mg (67%) of Compound I-41 as 
a light yellow solid. A sample was purified by column chromatography 
(EtOAc:PAW (pyr:HOAc:H.sub.2 O; 55:25:20)85:15), mp&gt;320.degree. C. .sup.1 
H NMR (DMSO-d.sub.6, 300 MHz): d 4.22 (s, 2H), 4.92 (s, 2H), 7.21-7.28 (m, 
2H), 7.38-7.55 (m, 2H), 7.60-7.65 (m, 3H), 7.70-7.85 (m, 4H), 8.6 (m, 2H), 
8.82 (s, 1H), 9.4 (m, 1H), 12.05 (s, 1H). MS m/e=414 (m+1).sup.+. 
EXAMPLE V(K)(8) 
Preparation of 
3-(2-(2-Pyridylethyl)-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7 
(7H)-one (Compound I-34) 
To Compound I-32 (Example V(K)(3) (460 mg, 1.1 mmol) in DMF (25 mL) was 
added a small spatula of raney nickel catalyst then the solution was 
hydrogenated at 40 psi for 12 h. The solvent was filtered through a pad of 
Celite.RTM., and then concentrated at reduced pressure. MeOH was added and 
the product collected to give 410 mg (89%) of Compound I-34 as a light 
yellow solid, mp&gt;300.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 
3.17-3.22 (bs, 4H), 4.15 (s, 2H), 4.89 (s, 2H), 7.22-7.41 (m, 5H), 7.51 
(d, 1H, J=8.2 Hz), 7.66-7.71 (m, 2H), 8.55 (s, 2H), 9.39 (d, 1H, J=7.5 
Hz), 11.82 (s, 1H). MS m/e=415 (m+1).sup.+. Anal. calc. for C.sub.28 
H.sub.21 N.sub.3 O.1.0 H.sub.2 O: C, 77.58; H, 5.35; N, 9.69. Found; C, 
77.54; H, 4.93; N, 9.35. 
EXAMPLE V(K)(9) 
Preparation of 
3-(2-Cyanoethenyl)-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H 
)-one (Compound I-35) 
To a solution of 
3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (100 mg, 0.26 mmol), cyanoacrylate (0.43 ml, 0.51 mmol) and 
triethylamine (0.5 mL) in DMF (3 mL) was added 
tetrakis(triphenylphosphine)palladium(0) (20 mg). The solution was heated 
in a sealed reaction tube at 100.degree.-110.degree. C. for 48 h. The 
mixture was cooled to ambient temperature, filtered through a pad of 
Celite.RTM., and the solvent was concentrated at reduced pressure. The 
product was triturated with MeOH to give 90 mg (97%) of a tan solid. 
Recrystallization from DMF-Et.sub.2 O gave Compound I-35 as a tan solid, 
mp&gt;330.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 4.2 (s, 2H), 5.0 
(s, 2H), 7.3-7.5 (m, 3H), 7.6-7.95 (m,4H), 8.35 (s, 1H), 8.65 (s, 1H), 9.4 
(d, 1H, J=9 Hz), 12.25 (s, 1H); IR: 2220 cm.sup.-1 ; MS m/e=362 
(m+1).sup.+. 
EXAMPLE V(K)(10) 
Preparation of 
3-Ethynyl-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-36) 
To a solution 
of3-bromo-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one 
(Compound I-9) (435 mg, 1.1 mmol), trimethylsilylacetylene (0.47 ml, 3.3 
mmol) and triethylamine (1.0 mL) in DMF (11 mL) was added 
bis(triphenylphosphine)palladium(II)chloride (17 mg). The solution was 
heated in a sealed reaction tube at 100.degree.-110.degree. C. for 24 h. 
The mixture was cooled to ambient temperature, filtered through a pad of 
celite then the solvent concentrated at reduced pressure. The product was 
dissolved in DMF (8 mL), MeOH (8 mL) cesium fluroide (370 mg, 2.4 mmol) 
added and the mixture stirred at ambient temperature 24 h. The solvent was 
concentrated at reduced pressure to give a dark solid. Purification by 
column chromatography (silica gel, EtOAc:MeOH; 10:1, Rf=0.53) give 30 mg 
of a tan solid. The compound was further purified by preparative TLC 
(silica gel, EtOAc:hexane; 3:1) to give Compound I-36 as a tan solid, 
mp&gt;300.degree. C. .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): d 4.2 (s, 2H), 5.0 
(s, 2H), 7.38-7.46 (m, 3H), 7.58-7.75 (m,4H), 8.15 (s, 1H), 8.63 (s, 1H), 
9.42 (d, 1H, J=9 Hz), 12.19 (s, 1H); MS m/e=335 (m.sup.+). 
EXAMPLE V(K)(11) 
Step-1: Preparation of 5-Pentyl-2-(2-(2-hydroxyindenyl))indole 
5-Pentyl-2-(2-(2-hydroxyindenyl))indole was prepared by substantially the 
same procedure as Example V(A)(1), step-1A, except that 2-indanone and 
5-pentylindole were used. 5-Pentyl-2-(2-(2-hydroxyindenyl))indole was 
immediately used in the next step. 
Step-2: Preparation of 5-Pentyl-2-(2-indenyl)indole 
Substantially the same procedure as Example V(A)(1), step-2A, was employed 
using 5-pentyl-2-(2-(2-hydroxyindenyl))indole (Step-1) to give the subject 
compound, mp 222.degree.-223.degree. C. .sup.1 H NMR (CDCl.sub.3, 300 
MHz): d 1.9 (m, 3H), 1.4 (m, 4H), 1.7 (m, 2H), 2.65 (m, 2H), 3.9 (s, 2H), 
6.6 s, 1H), 7.1 (m, 2H), 7.2-7.35 (m, 3H), 7.4 (m, 2H), 7.5 (d, 1H), 8.2 
(s, 1H). Anal. calc. for C.sub.22 H.sub.23 N: C, 87.66; H, 7.69; N, 4.65. 
Found; C, 87.33; H, 7.72; N, 4.58. 
Step-3: Preparation of 
3-Pentyl-4c,7a,7b,12a-tetrahydro-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]car 
bazole-5,7-(5H,7H)dione. 
A mixture of 5-pentyl-2-(2-indenyl)indole (Step-2) (300 mg, 1.0 mmol) and 
maleimide (193 mg, 2.0 mmol) in a 10 cm sealed reaction vial was heated at 
180.degree.-190.degree. C. for 1 h. After cooling to ambient temperature, 
the product was dissolved in MeOH (5 mL), and then concentrated at reduced 
pressure. The product was purified by column chromatography (silica gel, 
EtOAc:hexane; 2:1) to give 260 mg (66%) of the subject compound as a 
yellow foam. .sup.1 H NMR (CDCl.sub.3, 300 MHz): d 0.89 (t, 3H, J=5.5 Hz), 
1.26-1.35 (m, 4H), 1.63-1.67 (m, 2H), 2.68-2.75 (m, 2H), 2.94-3.02 (m, 
1H), 3.30-3.36 (m, 1H), 3.70-3.89 (m, 3H), 4.40 (m, 1H), 6.74 (s, 1H), 
7.05 (d, 1H, J=7.2 Hz), 7.14-7.39 (m, 5H), 7.80 (s, 1H), 7.98 (s, 1H). 
Step-4: Preparation of 
3-Pentyl-6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione 
(Compound I-37) 
To a solution of the product from step-3 (250 mg, 0.63 mmol) in toluene (15 
mL) was added solid 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (356 mg, 
1.57 mmol) in one portion. The solution was maintained at 
60.degree.-65.degree. C. for 6 hours. After cooling on an ice bath, the 
solids were collected by filtration. The product was purified by column 
chromatography (silica gel, EtOAc:hexane; 2:1) to give 75 mg (30%) of 
Compound I-37 as a dark solid. mp&gt;300.degree. C. .sup.1 H NMR (CDCl.sub.3, 
300 MHz): d 0.94 (m, 3H), 1.40 (m, 4H), 1.74 (m, 2H), 2.80 (m, 2H), 4.28 
(s, 2H), 6.96 (s, 1H), 6.4-6.6 (m, 3H), 7.8 (d, 1H, J=6.9 Hz), 7.8 (s, 
1H), 9.13 (d, 1H, J=7.2 Hz), 11.23 (s, 1H), 12.15 (s, 1H). MS m/e=393 
(m-1).sup.+. 
L. Specific Description of Synthetic Processes 
Preparation of Alkyl Fused Pyrrolocarbazoles 
Part XI: Allyl Derivatives 
EXAMPLE V(L)(1) 
Preparation of 
13-Allyl-5H,6H,12H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one (Compound 
I-26) 
5H,6H,12H,13H-Indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one (Compound I-2) 
(200 mg, 0.65 mmol) was added to a stirred solution of NaH (25 mg of 60% 
oil dispersion, 0.65 mmol) in dry DMF (10 mL) under a nitrogen atmosphere. 
The dark mixture was stirred at ambient temperature for 1 h, then allyl 
bromide (87 mg, 0.08 mL, 0.72 mmol) was added dropwise, and the mixture 
was stirred 12 hours at ambient temperature. The resulting yellow solution 
was concentrated at reduced pressure to give a solid. The product was 
crystallized from MeOH to give 90 mg (40%) of Compound I-26 as a yellow 
solid. The melting point was greater than 300.degree. C. The following NMR 
data were obtained: .sup.1 H NMR (DMSO-d.sub.6, 300 MHz): .delta. 3.45 (s, 
2H), 4.7 (d, 1H), 4.95 (s, 2H), 5.1 (d, 1H), 5.4 (s, 2H), 6.2-6.3 (m, 1H), 
7.35-7.45 (m, 3H), 7.55 (t, 1H), 7.7 (m, 2H), 8.05 (d, 1H, J=8 Hz), 8.6 
(s, 1H); 9.5 (d, 1H, J=9 Hz). MS(FAB): m/e 351 (m+1).sup.+. 
M. Specific Description of Synthetic Processes 
Preparation of Oxo Fused Pyrrolocarbazoles 
Part XII: Oxo Derivatives 
EXAMPLE V(M)(1) 
Preparation of 
12-Oxo-6H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione 
(Compound I-28) 
To a solution of CrO.sub.3 (465 mg, 4.65 mmol) in pyridine (20 mL) was 
added 6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione 
(Compound I-1), and the mixture was stirred at ambient temperature for 2.5 
days. An excess of THF was added and the solution was filtered through a 
pad of Celite.RTM.. The THF solution was washed well with saturated NaCl 
solution, then concentrated at reduced pressure to give an orange solid 
product. The product was recrystallized from THF-MeOH to give 270 mg (86%) 
of Compound I-28 as an orange solid. The melting point was greater than 
300.degree. C. The following NMR data were obtained: .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): .delta. 7.35 (t, 1H, J=6 Hz), 7.45 (t, 1H, J=6 
Hz), 7.6 (t, 1H, J=6 Hz), 7.7 (m, 3H), 8.7 (d, 1H, J=9 Hz); 8.9 (d, 1H, 
J=9 Hz), 11.6 (s, 1H), 12.4 (s, 1H). MS(FAB): m/e 338 (M.sup.+). 
EXAMPLE V(M)(2) 
7-Hydroxy-12-oxo-6H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5(5H)dione 
(Compound I-30) and 
5-Hydroxy-12-oxo-6H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)dione 
(Compound I-31). 
To a stirred solution of 
12-oxo-6H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-5,7(5H,7H)dione 
(Compound I-28) (75 mg, 0.22 mmol) in DMF/MeOH (10 mL, 1:1) was added 
solid sodium borohydride (50 mg, 1.3 mmol) in one portion. The mixture was 
stirred 14 h at ambient temperature, then concentrated at reduced 
pressure. MeOH was added and the product triturated to give 25 mg (33%) of 
a 2:1 mixture of Compound I-31:Compound I-30 as an orange solid. 
mp&gt;330.degree. C. .sup.1 H NMR(DMSO-d.sub.6 +D.sub.2 O, 300 MHz: .delta. 
6.32 (s, 0.33H), 6.4 (s, 0.66 H), 7.25-7.7 (m, 5H) 7.95 (d, 0.33H, J=6.7 
Hz), 8.25 (d, 0.67H, J=6.7 Hz), 8.76 (m, 0.67H), 8.9 (m, 1.33H). MS(FAB): 
m/e 341 (m+1).sup.+. 
N. Specific Description of Synthetic Processes 
Preparation of Lower Hydroxyalkyl Fused Pyrrolocarbazoles 
Part XIII: Lower Hydroxyalkyl Derivatives 
EXAMPLE V(N)(1) 
Preparation of 
13-(2-Hydroxyethyl)-5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7 
H)one (Compound I-29) 
5H,6H,12H,13H-indeno[2,3-a]pyrrolo[3,4-c]carbazole-7(7H)one (Compound I-2) 
(200 mg, 0.65 mmol) was added to a stirred solution of NaH (25 mg of 60% 
oil dispersion, 0.65 mmol) in dry DMF (10 mL) under a nitrogen atmosphere. 
The dark mixture was stirred at ambient temperature for 1 hour. Ethyl 
bromoacetate (120 mg, 0.08 mL, 0.72) was added dropwise and the mixture 
was stirred 12 hours. The resulting yellow solution was concentrated at 
reduced pressure to give a crude yellow solid. The product was dissolved 
in dry THF (10 mL) and lithium aluminium hydride (1 mL of 1M solution in 
ether) was added dropwise. The solution was stirred 6 hours at room 
temperature, then the reaction was quenched by the addition of H.sub.2 O 
(1 mL). The mixture was filtered and concentrated at reduced pressure. THF 
was added to the residue and the product was collected to give 30 mg (17%) 
of Compound I-29 as a white solid. The melting point was greater than 
300.degree. C. The following NMR data were obtained: .sup.1 H NMR 
(DMSO-d.sub.6, 300 MHz): .delta. 3.8-3.9 (b, 2H), 4.55 (s, 2H), 4.77 (t, 
2H), 4.9 (s, 2H), 5.0 (b, 1H, D.sub.2 O exchange), 7.3-7.45 (m, 3H), 
7.5-7.57 (t, 1H), 7.67 (d, 1H, J=6 Hz), 7.5 (d, 1H, J=6 Hz), 8.0 (d, 1H, 
J=6 Hz); 8.57 (s, 1H), 9.5 (d, 1H, J=7 Hz). MS(FAB): m/e 355 (M+1).sup.+. 
Although our invention has been described in considerable detail, those 
skilled in the art will appreciate that numerous changes and modifications 
may be made to the preferred embodiments of the invention and that such 
changes and modifications may be made without departing from the spirit of 
the invention. It is therefore intended that the appended claims cover all 
equivalent variations as fall within the true spirit and scope of the 
invention.