SUBSTITUTED INDOLES AS ANTI-AIDS PHARMACEUTICALS

Abstract: Substituted indoles of formula (I) are useful anti-AIDS pharmaceuticals.

Description: SUBSTITUTED INDOLES AS ANTI-AIDS PHARMACEUTICALS BACKGROUND OF THE INVENTION 1. Field of the Invention The oxygen and nitrogen substituted indoles described are useful in the treatment of AIDS. 2. Description of the Related Art International Publication No. WO 87/01797 discloses compounds which can be visualized as steroid-piperazine-[substituted aromatic] or steroid-piperazine-fsubstituted heteroaromatic]. The steroid and piperazine being "connected" via the C 17 side-chain of the steroid. International Publication No. WO 88/08424 disclosed compounds which can be visualized as aromatic-connector-piperazine-[substituted aromatic] or aromatic-connector-piperazine- [substituted heteroaromatic], in particular see the compounds of formulas (I) and (III). None of those compounds were disclosed as having the utility set forth in this invention. In U.S. Patent application 07/425,726, filed 10-23-89, it was disclosed that the compounds of formula (I) of International Publication No. WO 88/08424 were useful against AIDS. An estimated one to one and one-half million people in the United States are infected with a human retrovirus, the human immunodeficiency virus type I (HIV-1) which is the etiological agent of acquired immunodeficiency syndrome, AIDS, see Science, 661-662 (1986). Of those infected, an estimated two hundred and fifty thousands people will develop AIDS in the next five years, see Science, 1352-1357 (1985). On March 20, 1987, the FDA approved the use of the compound, AZT (zidovudine), to treat AIDS patients with a recent initial episode of pneumocystis carinii pneumonia, AIDS patients with conditions other than pneumocystis carinii pneumonia or patients infected with the virus with an absolute CD4 lymphocyte count of less than 200/mm 3 in the peripheral blood. AZT is a known inhibitor of viral reverse transcriptase, an enzyme necessary for human immunodeficiency virus replication. U.S. Patent 4,724,232 claims a method of treating humans having acquired immunodeficiency syndrome utilizing 3'-azido-3'-deoxy-thymidine (azidothymidine, AZT). It is known in the art that certain antibiotics and polyanionic dyes inhibit retrovirus reverse transcriptase. Many publications have reported the ability of various sulfated compounds to inhibit virus replication, including HIV. Nature 343, 470 (1990) and Science 250, 1411 (1990) discloses potent benzodiazepin type reverse transcriptase inhibitors. The compounds of the present invention are not benzodiazepin type compounds. US Patent 3,188,313 discloses compounds of the general formula [substituted indol-2-yl]-(CH2 . n -[piperazinyl type]-[pyridinyl/pyrimidinyl]. The substituted indoles (I) of the present invention differ from the prior art compounds in that the substitution on the -φ ring of the indole is a different group than that of the group in US Patent 3,188,313. US Patent 3,472,855 and 3,562,278 disclose 3-indolinyl compounds which are useful as psychomotor depressants. The substituted indoles (I) of the present invention are useful for a totally different purpose, inhibition of HIV-RT and treatment of AIDS. US Patent 3,362,956 discloses compounds of the general formula [3-quinolyl]-(CH2) n -[piperazinyl type]-[pyridinyl/ phenyl] . The substituted indoles (I) of the present invention differ from the prior art compounds in that they do not include 3-quinolyl type compounds. US Patent 3,472,854 discloses compounds of the general formula [2-benzimida_olyl]-(CH2) n -[piperazinyl type]-[pyridinyl/phenyl] . The substituted indoles (I) of the present invention differ from the prior art compounds in that they are indoles and not 2-benzimidazolyl type compounds. US Patent 3,491,098 discloses compounds of the general formula [4(5)-imid___oly_]-(CH2 . n -[piper_____yl type]-[pyrid__yl/phenyl]. The substituted indoles (I) of the present invention differ from the prior art compounds in that they are indoles and not imidazolyl type compounds. US Patent 3,511,841 discloses compounds of the general formula [azaindolyl]-(CH2) n -[piperazinyl type]-[pyridinyl/phenyl] [azaindolyl]-CO-[piperazinyl type]-[pyridinyl/phenyl] The substituted indoles (I) of the present invention differ from the prior art compounds in that they are they have substituted oxygen or substituted amino groups on the -φ portion of the indole and do not contain nitrogen in the ring. US Patent 4,302,589 discloses 3-indolinyl compounds with a methyl group at the C 2 position of the indole and an ethyl bridge between the indole and piperazine which are useful as anti-psychotics. The substituted indoles (I) of the present invention are useful for a totally different purpose, inhibition of HIV-RT and treatment of AIDS. European patent publication 345,808 discloses 3-indolinyl-piperazinyl-[substituted 2- pyridinyl] compounds (example 66) which are useful as anti-depressants. The substituted indoles (I) of the present invention are useful for a totally different purpose, inhibition of HIV-RT and treatment of AIDS. There are a number of other chemically unrelated compounds which have been reported to inhibit HIV and/or be useful in the treatment of AIDS. SUMMARY OF INVENTION Disclosed are substituted indoles of formula (I) where R j is -CH 2 - or -CO-; where Z j is where n j is 1 or 2 and n 2 is 1 or 2, where Z^ is -N(Z 2 _ι)- where Z2_ι is C j -C4 alkyl and where n j and n 2 are as defined above; where X j and X 2 are -H, -O-C r C 3 alkyl, -O-(CH 2 CH 2 -O-) n3 -X 1 . 1 where n 3 is 1 thru 4, where X 1 is -H or C r C 4 alkyl, -O-SO2-(CH2) n 4-N(X 1 . 2 )(Xi.3) where n is 1 thru 3, where X^ and X^ are the same or different and are -H, C j -Cg alkyl, -φ, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl and where X j _ 2 a ; X!_ 3 can be taken together with the attached nitrogen atom, and other heteroatom if necessary, to form a ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1- piperazinyl, 1-morpholinyl and 1-piperazinyl optionally substituted in the 4-position with C j -C; alkyl, in the 3- and/or 5- position with C j ^ alkyl, and N-oxides thereof -O-SO2-(CH2) n 4-Xi_g where X j .g is 2-pyridinyl, 3-pyridinyl and 4-pyridinyl and where n 4 is as defined above, -O-CO-(CH 2 ) n 4-NX 1 _ 2 X 1 _3 where n 4 , X 1-2 and X^ 3 are as defined above, -NH-CO-(CH2) n 4-NX 1 .2Xι.3 where n 4 , X^ and X^ 3 are as defined above, - (X 1 _4)-SO2-Xi_5 where X is C r C 3 alkyl, where X x _ 5 is C^ alkyl and where X j _4 and Xι_ 5 are taken together to form a heterocyclic ring of 5 or 6 atoms, -N(X 1 . 7 )-CO-N(X 1 . 7 )-(CH 2 ) n 4-N(X 1 . 2 )(X 1 . 3 ) where the X 1 7 s are the same or different and are -H or C j -C 3 alkyl, and where n 4 , X j _ 2 and X^ are as defined above, -N(X 1 _7)-SO 2 -(CH 2 ) I1 4-Xι_g where n 4 , X .η and X j .g are as defined above, -N(X 1 . 7 )-CO-N(X 1 . 7 )-(CH 2 ) n 5-X 1 .g where n 5 is 0 thru 3 and where ^η and X j .g are as defined above, -NX( 1 . 7 )-SO 2 -(CH 2 ) n4 -N(X 1 . 2 )(X 1 . 3 ) where n 4 , X { . 2 , X 3 and X j . 7 are as defined above, -NXd. 7 )-CO-O-X w where X^ is C r C 4 alkyl or •(CE 2 ) a4 -N(X 1 . 2 )(X 1 . 3 ) where n 4 , Xi_ 2 , Xι-3 and X j . 7 are as defined above, are as defined above, -NH-CO-CF3, -O-SO 2 -CF 3 , -NH-SO2-CF3, -N(X 1 . 7 )-SO 2 -N(X 1 _ 2 )(X 1 _3) where X . 2 , Xχ_3 and X j _ are as defined above, -NH-CO-^l-X^piperidinyl], with the proviso that one, but only one, of X! or X 2 must be -H or -O-C j -C 3 alkyl, R6 is -N=, -CH=, -N(O)=, R 7 is -COO-R 7 _ n where R 7 . n is C r C 6 alkyl, -CO-N(R _ 3 )(R _4) where R 7 _ 3 and R 7 _4 are the same or different and are -H or C r C 6 alkyl, -N(R 7 . 5 )(R 7 ^) where R 7 . 5 is -Cg alkyl, -C(R7-i5)(R7-i6)"(^7-i7) where R7.15 and 7.16 are the same or different and are -H or C^-C^ alkyl and where R7.17 is C2-C5 alkenyl containing 1 or 2 double bonds or C 2 -C 5 alkynyl containing 1 triple bond, -CH 2 -CH 2 -OH, -CH 2 -CH 2 -CH 2 -OH, -CH(CH 3 )CH 2 -O-CH 3 , -CH(CH 3 )CH 2 -OH, -CH 2 -CF 3 , -CH 2 -cyclopropyl, -CH 2 -CH 2 F, -CH 2 -CH 2 -C^N, -C*R 7 . 18 -(CH 2 ) nl4 -C*H 2 where R 7 . j g is -H or -CH 3 , n 1 is 1 thru 5 and the carbon atoms marked with an asterisk (*) are bonded to each other to resulting in the formation of a ring, -(CH2)n j -N(R 7 _ 7 )(R 7 _ 8 ) where n j is as defined above and where R 7 . 7 and R 7 . g are the same or different and are -H or C j -C 4 alkyl, and where R 7 . 7 and R 7 . 8 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrτolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, 1-aziridinyl, and where R 7 _g is -H, C r C 6 alkyl, -C(R _i5)(R 7 _ι 6 )-(R _ 1 7) where R7.15, R7-16 a* 10" R7-17 ar as defined above, -CH 2 -CH 2 -OH, -CH 2 -CH 2 -CH 2 -OH, -CH 2 CF 3 , -CH 2 "CH 2 F, -CH 2 -CH 2 -CsN, or where R7.5 and R 7 _g are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpho¬ linyl or 1-aziridinyl, -(CH 2 ) n 4-N(R7_9)(R 7 ..ι 0 ) where n is as defined above and where R 7 . 9 and R7.10 are the same or different and are -H or CJ-C4 alkyl, and where R7.9 and 7.10 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, R g is -N=, -CR 8 . 1 = where R^ is -H, -F, -Cl, -Br, -CF 3 , -NO 2 , -COCF3, C r C 6 alkyl, C r C 3 alkylthio, -OH, -O-Rg_ 2 where R g _ 2 is C j -Cg alkyl, -φ, -CO-R 8 . 3 where R 8 . 3 is C j -C 6 alkyl or -φ, -NH(R 8-t ) where R g _4 is -Cg alkyl, -C(Rg_7)(Rg.g)-(Rg_ 9 ) where Rg. 7 and R 8 . 8 are the same or different and are -H or ι~C 3 alkyl and where Rg_ 9 is C 2 -C 5 alkenyl containing 1 or 2 double bonds or C2-C5 alkynyl containing 1 triple bond, -NRg^-CO-Rg.g where R g _ 5 is -H or C C 6 alkyl and g^ is -H, ^-Cg alkyl or γ 3 alkoxy; __9 _s -N=, -CRg ^ where R 9 .! is -H, -F, -Cl, -Br, -NO 2 , -COCF3, C V C 6 alkyl, C r C 3 alkylthio, -OH, -O-R _ 2 where Rg_ 2 is C j -Cg alkyl, -φ, -CO-Rg_ 3 where R 9 _ 3 is C C 6 alkyl or -φ, -N R9_ )(R9_5) where Rg^ and R9.5 are the same or different and are -H, -Cg alkyl, -C(R9_g)(R9_9)-(R9_ 10 ) where R 9 . 8 and R9.9 are the same or different and are -H or C 3 alkyl and where R9.10 is C 2 -C 5 alkenyl containing 1 or 2 double bonds or C2-C5 alkynyl containing 1 triple bond, I_9_4 and R9.5 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1- piperazinyl or N-morpholinyl, -NRg.g-CO-R^ where Rg^ is -H or C r C 6 alkyl and Rg.η is -H, C r C 6 alkyl or C r C 3 alkoxy; R 10 is -N=, -O-lO-l^ where R 10 . 1 is -H, -F, -Cl, -Br, -CF 3 , -NO 2 , -COCF3, C r C 6 alkyl, C r C 3 alkylthio, -OH, -O-R 10 . 2 where R 10 _ 2 is C j -Cg alkyl, -φ, -CO-R 10 _. 3 where R 10 _ 3 is C j -Cg alkyl or -φ, -N(R 10 _j)(R 10 _5) where R10-4 and Rjo-5 are the same or different and are -H, -Cg alkyl, -C(R 10 _ )(R 10 _9)-(Rιo-io) where Rιo_g and JO-9 ^e the same or different and are -H or alk en _ 1 containing 1 or 2 double bonds or C 2 -C 5 alkynyl containing 1 triple bond, -NR 10 _ 6 -CO-R 10 _7 where JO- i s "** or C j -Cg alkyl and Rχo-7 is -H, C j -Cg alkyl or CJ-C3 alkoxy; with the proviso that not more than two of Rg, R 8 , R9 and R 10 are -N = ; enantiomers, pharmaceutically acceptable salts, hydrates and solvates thereof. Also disclosed are compounds selected from the group consisting of l-[5-(piperadin-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-((l-(l-methylethylpiperadin-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l-methylethyl___ ino)- 2-pyridinyl]piperazine, l-[5-methoxycarbamoylindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridyl]piperazine, l-[5-(r, -dioxo-2'-isothiazolidinyl)indolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridyl]piperazine, l-[5-(trifluoromethanesulfonamido)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridyl]piperazine. Further disclosed are compounds selected from the group consisting of l-[5-Aminoindole-2-carbonyl]-4-[3-(l,l-dimethylpropylamino)-2-pyridinyl]piperazine, 1 -[5-(methanesulfonamido)indole-2-carbonyl]-4-[3-(l , 1 -dimethylpropylamino)-2- pyridinyl]piperazine, l-[5-me anesulfona_nidoindole-2-carronyl]-4-[N-methyl-N-(3-(l,l-dime_ ylpropyl__Tiino)-2- pyridinyl)amino]piperidine, l-[6-(2-(l-piperadinyl)ethoxy)indolyI-2-carbonyl]-4-[3-(l-methylethyl-amino)-2- pyridinyl]piperazine, l-[5-methoxy-6-(2-(l-morphol_nyl)ethoxy)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine. DETAILED DESCRIPTION OF THE INVENTION The substituted indoles (I) of the present invention are prepared by known methods from known starting materials. The invention is the substituted indoles (I), not the methods to prepare them. For the substituted indoles (I), it is required with regard to X j or X 2 that one, but only one, of X j or X 2 must be -H or -O-C j ^ alkyl. Depending on whether the heteroatom attaching the X group to the indole is oxygen (-O-) or nitrogen (-NH-) the substituted indoles (I) are made by different procedures. When the heteroatom is an oxygen atom, the substituted indoles (I) are prepared as set forth in CHART A. CHART A exemplifies production of the substituted indole (I) with an oxygen atom at the 6-position of the indole nitrogen, at X 2 . However, it should be realized the synthetic process set forth in CHART A is equally applicable when the oxygen function is at the 5-position of the indole, at X j . The synthetic process begins with the appropriate hydroxyaldehyde (II). The hydroxyaldehyde (H) then has the remaining portion of the desired X group added, by known means, to form X-0-, to produce the substituted aldehyde (III). The substituted aldehyde (III) is then reacted with α-azidomethylester, preferably the acetate to form the corresponding azide (IV). The reaction is performed in a polar solvent, preferably an alcohol such as methanol and cooled to about -10°. A base such as sodium methoxide in methanol is added dropwise. The reaction is warmed to 20-25° until TLC indicates the reaction is complete. The azide (IV) is transformed to the corresponding indole ester (V) by heating to reflux in a solvent such as xylene. The indole ester (V) is then hydrolyzed to the corresponding indole acid (VI). The indole acid (VI) is the coupled with the desired amine substituent (Z j -aromatic portion) to form the substituted indole (I), see EXAMPLE 5. The desired amine substitutent (Z j -aromatic portion) are either known to those skilled in the art (in particular see International Publication No. WO 87/01797, PREPARATION A-l thru PREPARATION A-50) or can readily be prepared be prepared from known compounds by methods well known to those skilled in the art. The reaction of the indole acid (VI) and the desired amine substitutent (Z j -aromatic portion) is a very well known reaction. When Z j is the molecular fragment (Z-I) which is a piperazine, the amine substitutent is a secondary amine and the reaction with the appropriate indole acid (VI) produces an amide. Should the indole acid be reduced to an indole alcohol (R j is -CH 2 -), alkyl halide formed then the substituted indole (I) will be a tertiary amine. The reaction to produce tertiary amines or amides from cyclic amines such as piperazine is very well known to those skilled in the art and requires no special mention. See International Publication Nos. WO 87/01797 and WO 88/08424. When the heteroatom attaching the X group to the indole is a nitrogen, the substituted indoles are made by die process of CHART B. The amino indoles (VII) are known to those skilled in the art or can be readily be prepared by known means from known starting materials. The amino indoles (VH) are reacted with the sulfonyl chloride, CHCH^-SO^Cl (VIII) to produce the corresponding ethylene sulfonamide (DC). The ethyl ene sulfonamide (IX) is then reacted with the desired amine and powdered copper catalyst under reflux to produce the desired substituted indole (I). Similarly amino indoles (VH) can be reacted with Cl-(CH 2 ) 3 -SO 2 -Cl to produce the 3- chloropropylsulfonamid es. Alkylation with an amine would produce the desired substituted indoles. Alternatively, one can react the amino or hydroxy indole with functionalized sulfonyl chlorides, which are known in the art, such as 2-(4-pyridyl)ethane sulfonyl chloride to provide the sulfonamides or sulfonates directly. The process used for synthesizing the substituted indoles (I) where the atom attaching the X group to the indole is nitrogen does not work well when the atom is oxygen because if one starts with the hydroxy indole corresponding to the amino indole (VII), and attempts to alkylate as is done in the synthesis of compound (III), CHART A, then nitrogen atom of the indole would be competitively alkylated. This is not a problem with sulfonylation of the amino indole (VH) because the amino group on the benzene reacts preferentially over the indole nitrogen with R-SO 2 -leaving group. The amino indole (VII) can be transformed into the desired indole (I) where X j or X 2 is a urea (R g Rb-N-CO-NH-indole-) by reacting the free amino group on the indole with an isocyanate, by known means, see EXAMPLES 18-20. Another way to produce die substituted indole (I) where X j or X 2 is a urea is by reaction of the free amino group in the indole with phosgene (or a phosgene equivalent such as carbonyldiimidazole) and trapping with an amine. As is apparent to those skilled in the art, isothiocyanates or thiophosgene equivalents could be used to produce the corresponding -CS- compounds. Likewise, reaction of the amino indole (VII) with X-SO 2 -X followed by reaction with an amine produces sulfamides, R a R b N-SO2-NH-indole- by means known to those skilled in the art. The substituted indoles (I) where R j is -CH 2 - can be produced from the corresponding substituted indoles (I) where R j is -CO- by reaction with a reducing agent, such as lithium aluminum hydride in an ether such as tetrahydrofuran or ether. Alternatively, one can use starting materials in which R j is methylene rather than a carbonyl group. It is preferred that Z j is (Z-I) where n j and n 2 are 1. It is also preferred that Z j is is (Z- II) where n j and n 2 are 1. When Z j is Z-II it is preferred diat Z 2 . j is C j alkyl. It is preferred that R j is -CO-. It is preferred that R 6 is -N= . It is preferred that for R 8 , R9 and R 10 are Rg is -CRg_!= where R^ is -H, where -CRg.^ where Rg.^ is -H and where -CRI Q _I = where J Q -I is -H. It is preferred that R 7 is is -N(R 7 _5)(R 7 _g) where R7.5 is C 2 -C 4 alkyl and where R 7 ^ is -H. It is preferred that R7.5 is i-propyl. It is preferred that one of X j or X 2 is selected from the group consisting of It is preferred diat the other of X j or X 2 is -H or alkoxy. It is preferred that the substituted indole (I) is selected from the group consisting of compounds of EXAMPLES 5, 9, 14-20, 28-42, 44, 46-56, 58-61, 63-65, 67-69, 72, 75. It is more preferred that the substituted indole (I) is selected from the group consisting of compounds of EXAMPLES 35, 37, 42, 55, 57, it is even more preferred that the substituted indole (I) is selected from ώe group consisting of compounds of EXAMPLES 35, 37 and 57. Also preferred that the compound of the invention is the compound of EXAMPLE 76. The substituted indoles (I) are amines, and as such form acid addition salts when reacted widi acids of sufficient strength. Pharmaceutically acceptable salts include salts of both inorganic and organic acids. The pharmaceutically acceptable salts are preferred over the corresponding free amines since they produce compounds which are more water soluble and more crystalline. The preferred pharmaceutically acceptable salts include salts of die following acids methanesulfonic, hydrochloric, hydrobromic, sulfuric, phosphoric, nitric, benzoic, citric, tartaric, fumaric, maleic, CH3-(CH2) n -COOH where n is 0 thru 4, HOOC-(CH2 . n-COOH where n is as defined above. The substituted indoles (I) are useful as inhibitors of viral reverse transcriptase, an enzyme necessary for human immunodeficiency virus replication and therefore would be useful in the treatment of such diseases as AIDS. The term human retrovirus (HRV) indicates human immunodeficiency virus type I, or strains diereof apparent to one skilled in die art, which belong to die same viral families and which create similar physiological effects in humans as various human retroviruses. Patients to be treated would include diose individuals (1) infected with one or more than one strain of a human retrovirus as determined by me presence of eidier measurable viral antibody or antigen in die serum and (2) having eidier a symptomatic ADDS defining infection such as (a) disseminated histoplasmosis, (b) isopsoriasis, (c) bronchial and pulmonary candidiasis including pneumocystic pneumonia (d) non-Hodgkin's lymphoma or (e) Kaposi's sarcoma and being less than sixty years old; or having an absolute CD4 lymphocyte count of less than 200/m 3 in the peripheral blood. The substituted indoles (I) can be given orally. Suitable dosage forms include tablets, capsules, suspensions, solutions and elixirs. An effective amount is from about 0.1 to about 500 mg/kg/day. A typical unit dose for a 70 kg human would be from about 10 mg to about 2000 mg, preferably about 100 mg to about 1000 mg taken one to six times per day. The exact dosage and frequency of administration depends on ie particular substituted indole (I) used, the particular condition being treated, the severity of the condition being treated, the age, weight, general physical condition of die particular patient, odier medication die individual may be taking as is well known to diose skilled in die art and can be more accurately determined by measuring the blood level or concentration of the diaromatic substituted compounds (IH), the anti-AIDS piperazines (TV) and the indoles (V) in die patient's blood and/or the patient's response to die particular condition being treated. The substituted indoles (I) of this invention can be used in conjunction with other antiviral agents such as AZT. The utility of the substituted indoles (I) of this invention can be determined by their ability to inhibit viral reverse transcriptase, an enzyme essential for human immunodeficiency virus replication. This enzyme has characteristics which differentiate it from odier known cellular polymerases and it is a unique enzyme which is not found in uninfected cells. Viral reverse transcriptase is found in extracts from bacterial clones prepared according to the procedure described in AIDS Virus Reverse Transcriptase defined by high level expression in Escherichia coli, EMBO J. 6:3133-3137 (1987). Inhibition of this enzyme is determined in a cell free assay which measures the level of radioactive precursors incorporated into DNA. Extracts prepared according to the procedure of Science, 1125-1129 (1981) are incubated in a mixture of inhibitor, 20 mM dithiothreitol, 60 mM sodium chloride, 0.05% NP-40, 10 mM magnesium chloride, 50 mM Tris pH 8.3, 10 μM [ 35 S]-labeled deoxynuleoside-5'-triphosphate, 10 μg/ml RNA template (poly rC or poly rG) and 5 μg/ml DNA primer (oligo dG or oligo dT) for 30 minutes at 37 °C Incorporation of radio-labeled precursor is determined by spotting aliquots of the reaction mixture on DE81 paper, washing the papers to remove unincorporated precursor, drying and determining counts. The results $0 means the concentration, in μM of drug, required to inhibit the reverse transcriptase activity to die extent of 50%) of various assay (s) are combined and reported as % inhibition and IC 50 (calculated). The utility of this invention is further demonstrated by the ability of the substituted indoles (I) to inhibit HlV-induced syncytia formation in a tissue culture assay using MT-2 cells infected with HIV-1. This test is described in Quantitative Infectivity Assay for HIV-1 and -2., Nature 332: 469-470, 1988 as well as in AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol. 4, No. 6, pages 449-455 (1988), Mary Ann Liebent, Inc., Publishers; in an article entitled "Nucleotide Dimers Suppress HIV Expression In VITRO". The results (IC5 Q means me concentration, in μM of drug, required to inhibit syncytia formation to the extent of 50%) of various assay(s) are combined and reported as % inhibition and IC50 (calculated). The known commercial compound, AZT, exhibited anti-HIV potency in this assay with 100 percent and 50 percent reduction in syncytia formation at concentrations of approximately lμM and 0.5 μM, respectively. The exact dosage and frequency of administration depends on ie particular substituted indole (I) used, the particular condition being treated, die severity of die condition being treated, die age, weight, general physical condition of die particular patient, other medication the individual may be taking as is well known to those skilled in the art and can be more accurately determined by measuring die blood level or concentration of die substituted indoles (I) in the patient's blood and/or the patient's response to the particular condition being treated. DEFINITIONS AND CONVENTIONS The definitions and explanations below are for the terms as used throughout this entire document including both the specification and the claims. i. CONVENΓΠONS FOR FORMULAS AND DEFINITIONS OF VARIABLES The chemical formulas representing various compounds or molecular fragments in the specification and claims may contain variable substituents in addition to expressly defined structural features. These variable substituents are identified by a letter or a letter followed by a numerical subscript, for example, "Z j " or "R j " where "i" is an integer. These variable substituents are either monovalent or bivalent, that is, they represent a group attached to the formula by one or two chemical bonds. For example, a group Z j would represent a bivalent variable if attached to die formula CH 3 -C(=Z j )H. Groups R j and R; would represent monovalent variable substituents if attached to the formula CH 3 -CH 2 -C(R j )(R j )-H. When chemical formulas are drawn in a linear fashion, such as those above, variable substituents contained in parentheses are bonded to die atom immediately to die left of die variable substituent enclosed in parenthesis. When two or more consecutive variable substituents are enclosed in parendieses, each of die consecutive variable substituents is bonded to the immediately preceding atom to die left which is not enclosed in parentheses. Thus, in the formula above, both R j and R.- are bonded to die preceding carbon atom. Also, for any molecule with an established system of carbon atom numbering, such as steroids, diese carbon atoms are designated as C j , where "i" is die integer corresponding to die carbon atom number. For example, C 6 represents the 6 position or carbon atom number in the steroid nucleus as traditionally designated by diose skilled in die art of steroid chemistry. Likewise die term "Rg" represents a variable substituent (eidier monovalent or bivalent) at die C 6 position. Chemical formulas or portions thereof drawn in a linear fashion represent atoms in a linear chain. The symbol "-" in general represents a bond between two atoms in the chain. Thus CH 3 - O-CH 2 -CH(R j )-CH3 represents a 2-substituted-l-methoxypropane compound. In a similar fashion, the symbol " = " represents a double bond, e.g., CH 2 =C(__i)-O-CH3, and die symbol " ■ " represents a triple bond, e.g., HCasC-CH(R j )-CH 2 -CH 3 . Carbonyl groups are represented in either one of two ways: -CO- or -C(=O)-, with die former being preferred for simplicity. Chemical formulas of cyclic (ring) compounds or molecular fragments can be represented in a linear fashion. Thus, the compound 4-chloro-2-methylpyridine can be represented in linear fashion by N*=C(CH 3 )-CH=CC1-CH=C*H with the convention that die atoms marked with an asterisk (*) are bonded to each odier resulting in the formation of a ring. Likewise, the cyclic molecular fragment, 4-(ethyl)-l-piperazinyl can be represented by -N -(CH2)2-N(C2H 5 )-CH2- C*H 2 . A rigid cyclic (ring) structure for any compounds herein defines an orientation with respect to the plane of the ring for substituents attached to each carbon atom of die rigid cyclic compound. For saturated compounds which have two substituents attached to a carbon atom which is part of a cyclic system, -CQi^ζX^- the two substituents may be in eidier an axial or equatorial position relative to the ring and may change between axial/equatorial. However, the position of die two substituents relative to the ring and each other remains fixed. While either substituent at times may lie in the plane of the ring (equatorial) rather than above or below the plane (axial), one substituent is always above die odier. In chemical structural formulas depicting such compounds, a substituent (X j ) which is "below" anodier substituent (X^ will be identified as being in the alpha (α) configuration and is identified by a broken, dashed or dotted line attachment to die carbon atom, i.e., by die symbol " — " or "...". The corresponding substituent attached "above" (X^ die other (X j ) is identified as being in the beta (β) configuration and is indicated by an unbroken line attach- ent to die carbon atom. When a variable substituent is bivalent, the valences may be taken together or separately or both in the definition of die variable. For example, a variable R j attached to a carbon atom as -C(=R j )- might be bivalent and be defined as oxo or keto (ώus forming a carbonyl group (-CO-) or as two separately attached monovalent variable substituents α-R j _ j and fi-R j .^. When a bivalent variable, R j , is defined to consist of two monovalent variable substituents, the convention used to define the bivalent variable is of the form "α- R j _j:fi-Rj_ j -" or some variant thereof. In such a case bodi α-R j .j and β-R j __ are attached to die carbon atom to give -C(c_- R j _j)(β-R j _ ] -)-. For example, when the bivalent variable Rg, -C(=Rg)- is defined to consist of two monovalent variable substit¬ uents, the two monovalent variable substituents are cκ-R 6 _ 1 : β -R 6 _2» •••• <* __6-9 : ^"R6-10' etc, giving -C(α-Rg. 1 )(β-Rg.2)- -C(α-R 6 _9)(β-R 6 _ι 0 )-, etc. Likewise, for the bivalent variable R , For a ring substituent for which separate a and β orientations do not exist (e.g. due to the presence of a carbon carbon double bond in die ring), and for a substituent bonded to a carbon atom which is not part of a ring the above convention is still used, but die α and β designations are omitted. Just as a bivalent variable may be defined as two separate monovalent variable substituents, two separate monovalent variable substituents may be defined to be taken togedier to form a bivalent variable. For example, in the formula -Cι(R j )H-C2(Rj)H- (C j and C^ define arbitrarily a first and second carbon atom, respectively) R j and R: may be defined to be taken togedier to form (1) a second bond between C j and C_t or (2) a bivalent group such as oxa (-O-) and the formula tiiereby describes an epoxide. When R j and Rj are taken together to form a more complex entity, such as the group -X-Y-, tiien the orientation of the entity is such that C j in die above formula is bonded to X and C 2 is bonded to Y. Thus, by convention the designation "... R j and Rj are taken togedier to form -CH 2 -CH 2 -O-CO- ..." means a lactone in which the carbonyl is bonded to C 2 . However, when designated "... R: and R j are taken together to form -CO-O-CH 2 - CH 2 -dιe convention means a lactone in which the carbonyl is bonded to C j . The carbon atom content of variable substituents is indicated in one of two ways. The first method uses a prefix to the entire name of the variable such as "C j ^", where both "1" and "4" are integers representing die minimum and maximum number of carbon atoms in die variable. The prefix is separated from the variable by a space. For example, "^-C^ alkyl" represents alkyl of 1 through 4 carbon atoms, (including isomeric forms thereof unless an express indication to die contrary is given). Whenever this single prefix is given, the prefix indicates the entire carbon atom content of die variable being defined. Thus C 2 -C 4 alkoxycarbonyl describes a group CH 3 -(CH 2 ) J1 - O-CO- where n is zero, one or two. By the second method die carbon atom content of only each portion of the definition is indicated separately by enclosing the "C j -C j " designation in parendieses and placing it immediately (no intervening space) before the portion of the definition being defined. By this optional convention (C 1 -C 3 )alkoxy carbonyl has the same meaning as C 2 -C 4 alkoxycarbonyl because the "C1-C3" refers only to the carbon atom content of the alkoxy group. Similarly while both C 2 -C 6 alkoxyalkyl and (C 1 -C 3 )alkoxy(C 1 -C3)alkyl define alkoxyalkyl groups containing from 2 to 6 carbon atoms, the two definitions differ since die former definition allows either die alkoxy or alkyl portion alone to contain 4 or 5 carbon atoms while the latter definition limits either of diese groups to 3 carbon atoms. When die claims contain a fairly complex (cyclic) substituent, at die end of die phrase naming/designating that particular substituent will be a notation in (parendieses) which will correspond to the same name/designation in one of die CHARTS which will also set forth the chemical structural formula of that particular substituent. II. DEFINITIONS All temperatures are in degrees Centigrade. TLC refers to thin-layer chromatography. THF refers to tetrahydrofuran. DMF refers to dimethylformamide. EDC refers to l-ethyl-3-(dimedιylaminopropyl)carbodiimide. Saline refers to an aqueous saturated sodium chloride solution. IR refers to infrared spectroscopy. NMR refers to nuclear (proton) magnetic resonance spectroscopy, chemical shifts are reported in ppm (δ) downfield from tetramediylsilane. -φ refers to phenyl (C 6 H 5 ). MS refers to mass spectrometry expressed as m/e or mass/charge unit. [M + H] + refers to the positive ion of a parent plus a hydrogen atom. El refers to electron impact. Cl refers to chemical ionization. FAB refers to fast atom bombardment. Eώer refers to diethyl ether. Alcohol refers to ethyl alcohol. Pharmaceutically acceptable refers to those properties and/or substances which are acceptable to the patient from a pharmacological/toxicological point of view and to die manufacturing pharmaceutical chemist from a physical/chemical point of view regarding composition, formulation, stability, patient acceptance and bioavailability. Pharmaceutically acceptable anion salts include mesylate, chloride, sulfate, phosphate, nitrate, citrate, CH 3 -(CH 2 ) nl -COO "1 where n χ is 0 thru 4, ^OOC^CH^-COO "1 where n is as defined above, - 1 OOC-CH=CH-COO- 1 , ψ-COO '1 . When solvent pairs are used, the ratios of solvents used are volume/volume (v/v). When the solubility of a solid in a solvent is used die ratio of the solid to the solvent is weight/volume (wt/v). Pyridinyl refers to the pyridyl radical as defined by IUPAC nomenclature. For example 2-pyridyl refers to the pyridine ring substituted in the 2-position. The compounds of this invention are named (when possible) by the following method: first the [aryl/heteroaryl] moiety, next the aryl/heteroaryl portion and last the linker (Z). However, a few were named by odier methods for simplicity and convenience. The names of the radicals within each group follow IUPAC convention. EXAMPLES Without further elaboration, it is believed that one skilled in die art can, using the preceding description, practice die present invention to its fullest extent. The following detailed examples describe how to prepare die various compounds and/or perform the various processes of die invention and are to be construed as merely illustrative, and not limitations of the preceding disclosure in any way whatsoever. Those skilled in die art will prompdy recognize appropriate variations from the procedures both as to reactants and as to reaction conditions and techniques. PREPARATION 1 l-[l,l-Dimethyledιoxycarbonyl]-4-[3-φropylamino)-2-pyridinyl]- piperazine Sodium cyanoborohydride (0.31 g) is added to a cold solution of 1-[1,1- dimethyledιoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 2.8 g), propional (.87 g), and methanol (15 ml). After the exotherm has subsided, the reaction is stirred at 20-25° overnight. The reaction is acidified (pH 2) widi aqueous hydrochloride and then diluted with dichloromethane. The pH is adjusted with aqueous ammonium hydroxide (pH 8), and d e phases are separated. The organic phase is dried over sodium sulfate, and concentrated under reduced pressure to a crude product which is dissolved in diediyl ether and allowed to crystallize at -5°. The solid is identified as starting material. The mother liquor is concentrated in vacuo to give the title compound. PREPARATION 2 l-[3-(Propylamino)-2-pyridinyl]piperazine (Amine) Trifluoroacetic acid (4 ml) is added to a solution of crude l-[l,l-dimethylethoxycarbonyl]- 4-[3-propylamino)-2-pyridinyl]piperazine (PREPARATION 1, 1.2 g) in dichloromediane (15 ml) chilled to -78°. The coolant is removed and the reaction is allowed to warm to 20-25° for 3 hours. The solvents are removed in vacuo and die residue is redissolved in dichloromediane and aqueous saturated potassium carbonate. The phases are separated. The organic phase is washed with water, dried over sodium sulfate, and concentrated to die tide compound. PREPARATION 3 1-[1 , l-Dimethylethoxycarbonyl]-4-[3-(l-methylethylamino)-2- pyridinyljpiperazine l-[l,l-Dim__hyl__hoxyc__:bonyl]^[3-_miιιo-2-pyridinyl]piperazine (International Publication 88/08424, 2.0 g) is dissolved in 35 ml of methanol and acetone (0.48 g) is added. The reaction is cooled to 0° and acetic acid (to pH 4.0) is added. The reaction is stirred 15 min at 0° and d en sodium cyanoborohydride (0.50 g) is added. The reaction is allowed to warm slowly to 20-25° and followed by TLC until completion. Additional acetic acid, sodium cyanoborohydride and acetone are sometimes necessary to force the reaction to completion. The reaction is diluted with chloroform (100 ml), washed with saturated aqueous sodium bicarbonate (50 ml), saline (75 ml), dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (75 g silica gel, 4:1 hexane/ethyl acetate) affords the tide compound, NMR (300 MHz, CDCI 3 ) 7.67, 6.91, 4.15, 3.57, 3.00, 1.48 and 1.23 δ. PREPARATION 4 l-[3-(l-Medιyledιylamino)-2-pyridinyl]piperazine (Amine) l-[l,l-Dimethylethoxycarbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (PREPARATION 3) is dissolved in methylene chloride (56 ml) and cooled to 0°. Then trifluoroacetic acid is added dropwise. The reaction is warmed to 20-25° and additional trifluoro- acetic acid is added (26.6 g). When die reaction is complete by TLC, it is poured into 200 ml of water and ice, basified to pH 12 with 2N aqueous sodium hydroxide, and extracted with 10 % tetrahydrofuran/chloroform (21) followed by 10 % medianol/chloroform (1 1). The organic layers are dried over anhydrous sodium sulfate, concentrated in vacuo, and used widiout further purification, NMR (300 MHz, CDC1 3 ) 7.65, 6.85, 6.76, 4.16, 3.50, 2.98 and 1.20 δ. PREPARATION 6 2-Chloro-3-(l-methyledιylamino)pyrazine A solution of 2,3-dichloropyrazine (2.0 g) and isopropylamine (2.3 g) in toluene (8 ml) is refluxed for 40 hr. The mixture is cooled and filtered to remove isopropylamine hydrochloride. The filtrate is concentrated in vacuo to a residue which is diluted with an aqueous sodium hydroxide solution (10%) and dichloromediane. The phases are separated. The dichloromethane phase is washed widi saline, dried over sodium sulfate, and concentrated to give die tide compound, NMR (CDC1 3 ) 1.28, 4.21, 5.02, 7.54 and 7.94 δ. PREPARATION 7 l-[2-(l-Methylediylamino)-3-pyrazinyl]piperazine (Amine) A solution of 2-chloro-3-(l-methylethylamino)pyrazine (PREPARATION 6, 1.6 g) and piperazine (4.3 g) in xylene (10 ml) is refluxed for 26 hr. The mixture is cooled to 0° and diluted with concentrated hydrochloric acid (8 ml). The xylene is decanted and ether is added and also decanted from the salts. The salts are diluted with excess aqueous sodium hydroxide (5%) and dichloromediane. The phases are separated. The aqueous phase is extracted tiiree more times witii dichloromethane. The combined organic extracts are dried over sodium sulfate and concentrated to give a liquid mixture which is flash chromatographed on silica gel eluting with methanol/- chlorofoπn (5/95). The appropriate fractions are pooled and concentrated to give the tide com- pound, NMR (CDCI3) 1.27, 1.83, 3.04, 4.12, 4.78, 7.49 and 7.72 δ. PREPARATION 8 2-Chloro-3-(l , l-dimethylethylamino)pyrazine Following the general procedure of PREPARATION 6 but making non-critical variations but substituting t-butyl amine of risopropylamine, the tide compound is obtained, NMR (CDCI3) 1.48, 5.24, 7.51 and 7.91 δ. PREPARATION 9 l-[3-(l,l-Dimethylethylamino)-2-pyrazinyl]piperazine (Amine) Following the general procedure of PREPARATION 7 and making non-critical variations but starting with 2-chloro-3-(l,l-dimethylethylamino)pyrazine (PREPARATION 8, 0.95 g) and piperazine, die title compound is obtained, NMR (CDC1 3 ) 1.47, 1.70, 2.99, 5.02, 7.46 and 7.69 δ. PREPARATION 10 l-[l,l-Dimethyletiιoxycarbonyl]-4-[5-amino-6-pyrimidinyl]- piperazine A mixture of l-[l,l-dimedιyledιoxycarbonyl]-4-[4-chloro-5-nitro-6-pyrimidyl]piperazine and triethylamine (.3 ml) and palladium on carbon (5%, .13 g) in ethanol (100 ml) is charged with hydrogen gas (30 psi). After the theoretical amount of hydrogen gas is consumed, die catalyst is removed under reduced pressure. The filtrate is concentrated under reduced pressure to a foam which is diluted with an aqueous saturated solution of potassium carbonate and dichloromethane. The phases are separated and the organic phase is dried over sodium sulfate and concentrated to give to give the title compound, NMR (CDC1 3 ) 1.49, 3.49, 3.29, 3.56, 7.98, and 8.39 δ. PREPARATION 11 l-[l,l-Dimethylethoxycarbonyl]-4-[5-(l-methylethylamino)-6- pyrimidinyljpiperazine A solution of sodium cyanoborohydride (.13 g) in methanol (4 ml) is added to a mixture of 1-[1 , l-dimethyle_hoxycarbonyl]-4-[5-amino-6-pyrimidinyl]piperazine (PREPARATION 10, 0.44 g), acetone (3 ml), and glacial acetic acid (.4 ml) in methanol (7 ml) at 0°. The mixture is stirred at 20-25° for 72h. The reaction is diluted with an aqueous sodium hydroxide solution (10%) and dichloromediane. The phases are separated and d e organic phase is washed witi water and d e concentrated to a colorless liquid which is flash chromatographed on silica gel eluting with meώanol/chloroform (1/99). The appropriate fractions are pooled and concentrated to give the title compound, NMR (CDC1 3 ) 1.26, 1.49, 3.2, 3.44, 3.5-3.62, 7.89 and 8.33 δ. PREPARATION 12 l-[5-(l-Methyledιylamino)^-pyrimidinyl]piperazine (Amine) Trifluoroacetic acid (5 ml) is added to a solution of l-[l,l-dimethyletiιoxy- carbonyl]-4-[5- (l-methyledιylamino)-4-pyrimidinyl]piperazine (PREPARATION 11, 0.37 g) in dichloromethane (20 ml) at " 78°. The reaction is allowed to warm to 20-25° overnight, and dien diluted with excess aqueous sodium hydroxide solution (10%). The phases are separated. The aqueous phase is extracted twice again witii dichloromethane. The combined organic extracts are washed witii saline, dried over sodium sulfate, and concentrated under reduced pressure to give the tide compound, NMR (CDC1 3 ) 1.25, 1.7, 3.01, 3.21, 3.45, 3.5, 7.86 and 8.34 δ. PREPARATION 13 l-[4-(l-Medιylethyl)amino-3-pyridazinyl]piperazine (Amine) Following the general procedure of PREPARATION 10 and making non-critical variations butst__Λingwithl-[5-chloro-4-(l-meΛyledιyl)amino-3-pyridazinyl]piperazine(PREPARAΗON42, 1.7 g) and triediylamine (.81 g), the title compound is obtained, NMR (CDC1 3 ) 1.28, 2.06, 3.05, 3.11, 3.59, 4.75, 6.39, and 8.49 δ; CMR (CDC1 3 ) 22.2, 43.2, 46.2, 50.6, 103.7, 138.7, 148.4 and 154.5 δ. PREPARATION 16 l-[l,l-Dimethylethoxycarbonyl]^-[3-(l-pyrrolidinyl)-2-pyridinyl]- piperazine l-[l,l-Dimedιyle_ιoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 0.50 g), 1,4-dibromobutane (0.21 ml) and potassium carbonate (0.30 g) are refluxed in 4 ml of acetonitrile for 1 week. After 1 week, additional dibromobutane (0.21 ml) is added and refluxing is continued for 3 days. The reaction mixture is poured into water, extracted with methylene chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography eluting with ethyl acetate hexane (10/90) to etiiyl acetate/hexane (25/75). The appropriate fractions are pooled and concentrated to give the tide compound, NMR (300 MHz, CDC1 3 ) 7.78, 6.98, 6.78, 3.52, 3.20-3.10, 1.87 and 1.44 δ. PREPARATION 17 l-[3-(l-Pyrrolidinyl)-2-pyrid_nyl]piperazine (Amine) l-[l, l-Dimethylethoxycarbonyl]-4-[3-(l-pyrrolidinyl)-2-pyridinyl]piperazine (PREPARATION 16, 0.26 g) is dissolved in 1.3 ml of THF and cooled to 0°. Trifluoroacetic acid (1.3 ml) is added and die reaction is stirred at 0° for 20 min, and then warmed to 20-25° for 20 min. Then the reaction is poured into 1 N aqueous sodium hydroxide and extracted witii medianol/chloroform (10/90, 2 X 50 ml), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give die title compound, NMR (300 MHz, CDC1 3 ) 7.64, 6.81, 6.61, 3.05-2.94, 2.86-2.79 and 1.78-1.65 δ. PREPARATION 21 l-(3-Nitro-2-pyridinyl)-l,4-diazepine Homopiperazine (15.58 g) is dissolved in 100 ml of acetonitrile. Potassium carbonate (8.7 g) is added and then die 2-chloro-3-nitropyridine (5.0 g) dissolved in 25 ml of acetonitrile is added dropwise. The reaction is stirred at 20-25° 4 hr, then diluted widi methylene chloride, washed with water (2 x), saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound, NMR (300 MHz, CDCI3) 8.30, 8.08, 6.66, 3.60, 3.41, 3.10, 2.89 and 1.93 δ. PREPARATION 22 l-(l,l-Dimethylethoxycarbonyl)-4-(3-nitro-2-pyridinyl)-l,4- diazepine Following die general procedure of PREPARATION 19 and making non-critical variations but starting with l-(3-nitro-2-pyridinyl)-l,4-diazepine (PREPARAΗON 21, 7.06 g), the tide compound is obtained, NMR (300 MHz, CDC1 3 ) 8.29, 8.05, 6.67, 3.76-3.29, 1.98, 1.34 and 1.29 δ. PREPARAΗON 23 l-(l,l-Dimethylethoxycarbonyl)-4-(3-amino-2-pyridinyl)l,4- diazepine Following the general procedure of PREPARAΗON 52 and making non-critical variations but starting with l-(l,l-dimethyletiioxycarbonyl)-4-(3-nitro-2-pyridinyl)-l,4-diazepine (PREPARAΗON 22, 6.0 g), title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.75, 6.93, 6.81, 3.86, 3.78, 3.66-3.57, 3.51, 3.36-3.2, 3.21, 1.95, 1.85, 1.48 and 1.47 δ. PREPARAΗON 24 l-(l,l-D_methylethoxycarbonyl)-4-(3-ethylamino-2-pyridinyl)-l,4- diazepine Following die general procedure of PREPARATION 1 and making non-critical variations but starting with l-(l,l-dimethylethoxycarbonyl)-4-(3-amino-2-pyridinyl)-l,4-diazepine (PREPARAΗON 23, 6.07 g) and acetaldehyde for propional, die title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.65, 6.86, 6.76, 4.25, 4.11, 3.64-3.48, 3.30-3.21, 3.12-3.08, 1.92, 1.83, 1.47, and 1.45 δ. PREPARATION 25 l-(3-Ethylamino-2-pyridinyl)-l,4-diazepine (Amine) Following the general procedure of PREPARATION 4 and making non-critical variations but starting with l-(l,l-dimethyledioxycarbonyl)-4-(3-ethylamino-2-pyridinyl)-l,4-diazepine (PREPARAΗON 24, 5.12 g), the title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.66, 6.85, 6.76, 4.17, 3.31-3.26, 3.14-3.01, 1.84 and 1.29 δ. PREPARAΗON 26 l-(l,l-Dimethylethoxycarbonyl)-4-(3-(l-methylethyl)amino-2- pyridinyl)-l ,4-diazepine Following the general procedure of PREPARAΗON 3 and making non-critical variations but starting with l-(l,l-dimethylethoxycarbonyl)-4-(3-amino-2-pyridinyl)-l,4-diazepine (PREPARAΗON 23, 18.13 g), the title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.62, 6.85, 6.76, 4.18, 3.63-3.48, 3.28-3.19, 3.07, 1.92, 1.83, 1.46, 1.45 and 1.23 δ. PREPARAΗON 27 l-(3-(l-Methyledιyl)amino-2-pyridinyl)-l,4-diazepine (Amine) Following the general procedure of PREPARATION 4 and making non-critical variations but starting with l-(l,l-dimedιyledιoxycarbonyl)-4-(3-(l-medιyledιyl)-2-pyridinyl)-l,4-diazepine (PREPARATION 26, 15.08 g), the title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.61, 6.82, 6.75, 4.17, 3.50, 3.28-3.22, 3.06-3.01, 2.67, 1.83 and 1.20 δ. PREPARATION 28 l-[l,l-Dimedιyletiιoxycarbonyl]-4-[3-(l-methylpropyl)amino-2- pyridinyl]piperazine Following the general procedure of PREPARAΗON 3 and making non-critical variations but starting with 1-[1 , l-dimedιyledιoxyc__rbonyl]-4-[(3-an_ino)-2-pyridinyl)piper___ine (International Publication No. WO 88/08424, 1.0 g), 2-butanone (0.27 g) sodium cyanoborohydride (0.23 g), acetic acid (5.1 ml) and methanol, the title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.68, 6.94, 6.86, 4.18, 3.56, 3.33, 3.05, 1.53, 1.47, 1.18 and 0.96 δ. PREPARAΗON 29 l-[3-(l-Metiιylpropyl)amino)-2-pyridinyl]piperazine Following the general procedure of PREPARAΗON 4 and making non-critical variations butstartingwithl-[l,l-dimetiiylethoxycarbonyl]-4-[3-(l-methylpropyl)amino-2-pyridinyl)piperazine (PREPARAΗON 28, 1.62 g), trifluoroacetic acid (5.52 g) and 10 ml of methylene chloride, the title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.66, 6.87, 6.78, 4.17, 3.31, 3.06, 2.81, 1.64-1.48, 1.17 and 0.95 δ. PREPARAΗON 30 l-[Benzyloxycarbonyl]-4-[3-(l-ethylpropylamino)-2-pyridinyl]- piperazine Following the general procedure of PREPARAΗON 3 and making non-critical variations but starting witii l-[benzyloxycarbonyl]-4-[(3-amino)-2-pyridinyl]piperazine (PREPARATION 33, 10.5 g), 3-pentanone (0.15 g) sodium cyanoborohydride (0.11 g), acetic acid (52.3 ml) and methanol (3.2), the title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.66, 7.38-7.33, 6.90, 6.79, 5.17, 4.21, 3.65, 3.15, 3.04, 1.66-1.46 and 0.93 δ. PREPARAΗON 31 l-[3-(l-Ethylpropyl)amino-2-pyridinyl]piperazine Starting with l-[l-benzyloxycarbonyl]-4-[(3-(l-ethylpropylamino)-2-pyridinyl)piperazine (PREPARAΗON 30, 0.30 g) and using 10% palladium on carbon (30 mg) and ethyl acetate (10 ml), the protecting group is removed to give the title compound, NMR (300 MHz, CDC1 3 ) 7.65, 6.87, 6.78, 4.19, 3.40-3.10, 3.00-2.75, 1.64-1.49, and 0.93 δ. PREPARAΗON 32 l-[Benzyloxycarbonyl]-4-[3-nitro-2-pyridinyl]piperaz ne l-(3-Nitro-2-pyridinyl)piperazine is dissolved in 175 ml of methylene chloride and cooled to 0°. Then pyridine is added followed by benzylchloroformate (16.5 ml). The reaction is stirred 1.5 hr, tiien poured into saturated aqueous sodium bicarbonate and extracted widi chloroform, dried over anhydrous sodium sulfate and concentrated in vacuo to afford die title compound, NMR (300 MHz, CDCI3) 8.34, 8J5, 7.38-7.32, 6.81, 5.17, 3.65 and 3.45 δ. PREPARAΗON 33 l-Penzyloxycarbonyl]^-[3-amino-2-pyridinyl]piperazine l-[Be_zyloxycarbonyl]-4-[3-nitro-2-pyridinyl]piper___ine(PREPARAΗON 32), is dissolved in dioxane (923 ml) and cooled to 0°. Then aqueous titanium trichloride (20%, 555.3 ml) is added cautiously. After stirring 30 min the reaction is diluted widi aqueous sodium hydroxide solution (2 N, 1.5 1) and filtered through celite. The filter cake is washed widi methanol/chloroform (10/90). The combined organic layers are washed widi water, saline, dried and concentrated in vacuo to afford the desired product, NMR (300 MHz, CDC1 3 ) 7.80, 7.38-7.32, 6.99, 6.88, 5.17, 3.67 and 3.12 δ. PREPARAΗON 34 1 -[Benzyloxycarbonyl]-4-[3-(2,2,2-trifluoroacetamido)-2-pyridin- yljpiperazine l-[Benzyloxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (PREPARAΗON 33), is dissolved in 50 ml of methylene chloride and triethylamine is added. The reaction is cooled to 0° and trifluoroacetic anhydride is added dropwise. After 30 min, die reaction is poured into saturated aqueous sodium bicarbonate solution and extracted wid chloroform, washed widi saline, dried over anhydrous sodium sulfate and concentrated in vacuo, NMR (300 MHz, CDC1 3 ) 8.92, 8.54, 8.22, 7.39-7.32, 7.16, 5.17, 3.70 and 3.03 δ. PREPARAΗON 35 l-[3-(2,2,2-Trifluoroacetamido)-2-pyridinyl]piperazine l-[Benzyloxycarbonyl]-4-[3-(2,2,2-trifluoroacetamido)-2-pyridinyl]piperazine (PREPARAΗON 34), is dissolved in 70 ml of ethanol and 0.25 g of 10% palladium on carbon is added. The reaction is hydrogenated at 40 psi for 20 hr. Then it is filtered through a pad of celite and concentrated in vacuo to afford die title compound which is used without further purification, NMR (300 MHz, CDC1 3 ) 8.51, 8.21, 7.19, and 3.45-3.47 δ. PREPARAΗON 36 l-[3-(2,2,2-trifluoroethylamino)-2-pyridinyl]piperazine l-[3-(2,2,2-Trifluoroacetamido)-2-pyridinyl]piperazine (PREPARAΗON 35), is dissolved in 5 ml of tetrahydrofuran and cooled to 0°. Then 4.84 ml of lithium aluminum hydride solution is added dropwise. After 10 min of stirring at 0°, the reaction is warmed to 20-25° and stirred 45 min. The reaction is quenched at 0° widi the dropwise addition of 0.4 ml of water, 0.6 ml of 10% aqueous sodium hydroxide, and 1 ml of water. The slurry is filtered through celite, washed with 20% methanol/chloroform and concentrated in vacuo to afford the title amine which is used widiout further purification, NMR (300 MHz, CDC1 3 ) 7.82, 6.97-6.92, 4.86, 3.75, and 3.06-3.01 δ. PREPARAΗON 37 l-[3-(2-Fluoroacetamido)-2-pyridinyl]piperazine Following die general procedure of PREPARAΗON 35 and making non-critical variations but starting widi l-benzyloxycarbonyl-4-[3-(2'-fluoroacetamido) -2-pyridinyl]piperazine (2.42 g), 10% palladium on carbon (0.25 g), die title compound is obtained, NMR (300 MHZ, CDC1 3 ) 8.15, 7.97, 7.00, .88, 4.73 and 3.13 δ. PREPARAΗON 38 l-[3-(2-Fluoroethylamino)-2-pyridinyl]piperazine Following the general procedure of PREPARATION 36 and making non-critical variations but starting with l-[3-(2-fluoroacetamido)-2-pyridinyl]- piperazine (PREPARAΗON 37, 1.4 g), lithium aluminum hydride (11.76 ml, 1M in tetrahydrofuran), the title compound is obtained. PREPARAΗON 39 l-[l,l-Dimethylethoxycarbonyl]-4-[4-chloro-5-nitro-6-pyrimidyl]- piperazine A solution of l-[l,l-dimedιyledιoxycarbonyl]piperazine (1.88 g) in dichloromediane (30 ml) is added drop by drop over 1.5 hr to a solution of 4,6-dichloro-5-nitropyrimidine (1.94 g) and triethylamine (1.32 g) in dichloromethane (170 ml) at 78°. After stirring an additional hr at -78°, the reaction is diluted widi aqueous sodium bicarbonate (10%). The phases are separated, die organic phase is concentrated to a liquid which solidified on standing at 20-25°. The solid is dissolved in chloroform and flash chromatographed on silica gel eluting with methanol/chloroform (1/99), pooling and concentrating the appropriate fractions gives the title compound, Anal. Calc for C 13 H 18 N 5 ClO 4 ; MW = 343.77: C, 45.42; H,5.28; N,20.37; Cl.10.31. Found: C . 45.52; H,5.40; N,20.34; Cl, 10.36. PREPARAΗON 40 l-[3-(l-Methyledιylamino)-2-pyrazinyl]-l,4-diazepine (Amine) Following the general procedure of PREPARAΗON 7 and making non-critical variations but starting with homopiperazine (2.46 g) and 2-chloro-3-(l-methylediyI)aminopyrazine (PREPARAΗON 6), the title compound is obtained, NMR (300 MHz, CDC1 3 ) 7.56, 7.34, 4.75, 4.04, 3.28-3.18, 3.00-2.94, 1.79, and 1.15 δ. PREPARAΗON 41 3,5-Dichloro-4-(l-methylethylamino)pyridazine A solution of 3,4,5-trichloropyridazine (9.2 g) and isopropylamine (16.5 g) in toluene (25 ml) is refluxed for 18 hr. Excess isopropylamine is removed by atmospheric distillation. The residual solution is cooled and diluted widi dichloromethane and aqueous sodium hydroxide solution (5%). The phases are separated. The organic phase is washed widi water and tiien widi saline. The organic phase is dried over sodium sulfate and concentrated under reduced pressure to give a liquid which contains a mixture of isomeric products. The isomers are separated by flash chromatography on silica gel eluting widi ether/hexane (30/70). The appropriate fractions are pooled and concentrated to give die desired isomer, NMR (CDC1 3 ) 1.33, 4.59, 4.87 and 8.60 δ; CMR (CDC1 3 ) 24.2, 46.4, 117.1, 139.3, 145.5 and 151.3 δ. Further elution gives 3,4-dichloro-5-(l-metiιyletiιylamino)pyridazine which is recrystallized from ether hexane, NMR (CDC1 3 ) 1.35, 3.87, 4.80, and 8.55 δ; CMR (CDC1 3 ) 22.6, 44.7, 116.5, 136.3, 142.5 and 153.4 δ. PREPARAΗON 42 l-[5-Chloro-4-(l-methylethyl)amino-3-pyridazinyl]piperazine A mixture of 3,5-dichloro-4-(l-methyletiιyl)aminopyridazine (PREPARAΗON 41, 1.77 g) and piperazine (2.96 g) in xylene (18 ml) is refluxed for 40 hr. The mixture is cooled and then treated widi concentrated hydrochloric acid (8 ml). After further cooling, a precipitate forms and die organic liquid is separated. The aqueous phase is diluted widi an excess of a solution of aqueous sodium hydroxide (10%) and then is extracted widi chloroform (3 x). The combined organic extracts are washed widi water, tiien saline, dried over sodium sulfate, and concentrated to an oil. The crude product is flash chromatographed on silica gel eluting widi metiianol. The appropriate fractions are pooled and concentrated to give die title compound, NMR (CDCI3) 1.20, 3.04, 3.18, 4.46, 4.73 and 8.50 δ; CMR (CDC1 3 ) 24.0, 44.3, 45.9, 50.2, 118.2, 135.8, 148.3 and 155.4 δ. PREPARAΗON 43 3,5-Dichloro-4-(l,l-dimedιyledιylamino)pyridazine Following the general procedure of PREPARATION 41 and making non-critical variations but starting widi t-butylamine (66.5 ml), and 3,4,5-trichloropyrid___ine, the title compound is obtained, NMR (300 MHz, CDC1 3 ) 8.50, 5.09, and 1.55 δ. PREPARAΗON 44 l-[5-Chloro-4-(l, l-dimethylediylamino)-3-pyridazinyl]piperazine Following the general procedure of PREPARAΗON 42 and making non-critical variations but starting with 3,5-dichloro-4-(l , l-dimediylediylamino)pyridazine (PREPARAΗON 43), the title compound is obtained, NMR (300 MHz, CDC1 3 ) 8.55, 5.04, 3.25, 3.07, and 1.44 δ. PREPARAΗON 45 l-[4-(l,l-Dimethylethylamino)-2-pyridazinyl]piperazine (Amine) Following the general procedure of PREPARAΗON 10 and making non-critical variations butstartingwith 1 -[5-chloro-4-(l , 1 -dimedιylethylamino)-3-pyridazinyl]piperazine(PREPARAΗON 44), and triethylamine (4.6 ml), the title compound is obtained, NMR (300 MHz, CDC1 3 ) 8.53, 6.79, 5.57, 3.55, and 1.47 δ. PREPARAΗON 46 1-[1 , l-Dimethylethoxycarbonyl]-4-[3-(2-propenylamino)- 2-pyridinyl]piperazine A mixture of l-[l,l-dimethylethoxycarbonyl]-4-[3-amino-2-pyridinyl]-piperazine (International Publication 88/08424, 2.78 g), 3-bromopropene (1.87 g), anhydrous potassium carbonate (3.3 g) and acetonitrile (100 ml) is refluxed for 36 hr. The mixture is cooled and then diluted with dichloromediane and aqueous potassium carbonate solution. The phases are separated and d e organic phase is washed with saline and than concentrated in vacuo. Purification by flash column chromatography (2% methanol/chloroform) provided of the tide compound. Capillary GC analysis (HP1 column, initial temperature at 100° for 1 min, then programmed to rise 20° per minute to 250°) gave a peak at 6.06 (96%) minutes. PREPARAΗON 47 l-[3-(2-Propenylamino)-2-pyridinyl]piperazine Following the procedure of PREPARAΗON 2 and making non-critical variations but starting with l-[l,l-dimedιyledιoxycarbonyl]-4-[3-(2-propenyl)-2-pyridinylamino]piperazine (PREPARAΗON 46, 0.7 g), the title compound is obtained. TLC analysis (silica gel, eluent: 15% methanol/chloroform, visualization with UV light and iodine vapor) showed one spot, Rf = 0.1. PREPARATION 48 l-(l,l-Dimedιyledιoxy)carbonyl-4-methylaminopiperidine Mediylamine hydrochloride (2.36 g) is dissolved in metiianol (50 ml) and potassium hydroxide pellets (0.60 g) and N-(l,l-di-medιyledιoxycarbonyl)-4-piperidone are added. Sodium cyanoborohydride (0.69 g) in metiianol (5 ml) is added and die mixture is stirred 2 hrs. Potassium hydroxide pellets (1.96 g) are added to the mixture which is stirred 1 hr and acidified to pH 2 widi 6M hydrochloric acid and concentrated. The mixture is diluted widi water (50 ml) and extracted with edier (3 x 80 ml) which is discarded. The aqueous layer is basified to pH 11 with potassium hydroxide pellets, saturated with sodium chloride and extracted with ether (6 x 80 ml). The combined organic extracts are dried widi magnesium sulfate and concentrated to afford an oil which is chromatographed on silica gel with a methanol/chloroform gradient (5-30%). Fractions are pooled on die basis of TLC (Rf = 0.13, 20% medianol/chloroform) to give the tide product, NMR (CDC1 3 ) 4.04, 2.79, 2.54, 2.46, 2.33, 1.88, 1.46, and 1.26 δ. PREPARAΗON 49 1-(1, l-Dimethylethoxy)carbonyl)-4-(N-methyl-N-(3-nitro-2- pyridinyl)am_no)piperidine Anhydrous potassium carbonate (2.71 g) and 2-chloro-3-nitropyridine (0.93 g) are added to a solution of l-((l,l-dimedιyletiιoxy)carbonyl)-4-methylaminopiperidine (PREPARAΗON 48, 1.40 g) in acetonitrile (50 ml). The mixture is stirred 21 hours at 20-25° and additional 2-chloro- 3-nitropyridine (100 mg) and acetonitrile (5 ml) are added. The mixture is stirred 2.8 days, concentrated and dissolved in mediylene chloride (175 ml) and water (50 ml). The phases are separated and die organic phase is extracted widi water (2 x 50 ml) and saline (40 ml) and dried over sodium sulfate. Concentration under reduced pressure affords an oil which is chromatographed on silica gel (120 g) eluting with 10% etiiyl acetate/hexane. Fractions with Rf = 0.29 by TLC (silica gel, 25% ethylacetate/hexane) are pooled and concentrated to give die title compound, NMR (CDC1 3 ) 8.29, 8.11, 6.68, 4.62, 4.26, 2.85, 2.67 and 1.48 δ. PREPARAΗON 50 4-(N-medιyl-N-(3-nitro-2-pyridinyI)amino)piperidine Trifluoroacetic acid (13.0 ml) is added to a solution of 1-((1 , l-dimedιyletiιoxy)carbonyI)-4- (N-medιyl-N-(3-nitro-2-pyridinyl)amino)piperidine (PREPARAΗON 49) in methylene chloride (100 ml) with cooling to -78°. The mixture is warmed to 20-25°, stirred 17 hrs, cooled to 0° and basified to pH 12 with 5% sodium hydroxide. The phases are separated and die aqueous phase is extracted with methylene chloride (2 x 50 ml). The combined organic phases are dried over sodium sulfate and concentrated to give die title compound, mp 115.5-117°. PREPARAΗON 52 1-(1 , l-Dimethylethoxyl)carbonyl)-4-(N-methyl-N-(3-amino-2- pyridinyl)amino)piperidine l-(l,l-Dimethyledιoxy)carbonyl)-4-(N-methyl-N-(3-nitro-2-pyridinyl)amino)piperidine (PREPARAΗON 49, 7.49g) is dissolved in ethanol (135 ml) and palladium on carbon (10%, 0.65 g) is added. The reaction is hydrogenated at 40 psi for 18 hours and filtered dirough a pad of celites and concentrated under reduced pressure, NMR (d-methanol) 7.54, 6.99, 6.80, 3.90, 2.61, 2.56, 1.63, 1.47 and 1.35 δ. PREPARAΗON 53 l-(l, l-Dimethylethoxyl)carbonyl)-4-(N-methyl-N-(3-(l- methyletiιylamino-2-pyridinyl)amino)piperidine l-(l,l-Dimethylethoxy)carbonyl)-4-(N-medιyl-N-(3-amino-2-pyridinyl)amino)piperidine (PREPARAΗON 52) is dissolved in ethanol (137 ml) and cooled to 0°. Glacial acetic acid (39.3 ml) and acetone (2.22 ml) are added. After 15 min sodium cyarboborohydride (4.99 g) is added and die reaction is warmed to 20-25°. Since reaction did not appear complete by TLC (ethyl acetate/hexane, 75/25), a total of 3.5 equivalents of acetone and acetic acid are added over a 24 hour period. The reaction is poured into water, extracted with chloroform, dried over sodium sulfate and concentrated under reduced pressure. Flash column chromatography eluting with ethyl acetate/hexane (20/80), pooling die appropriate fractions and concentrating gives die title compound, NMR (d-methanol) 7.47, 6.90, 3.92, 3.51, 2.71, 2.51, 1.35, 1.61 and 1.11 δ. PREPARAΗON 54 4-(N-Methyl-N-(3-(l-methylethylamino)-2-pyridinyl)amino)- piperidine Following the procedure of PREPARAΗON 50, but substituting 1-(1,1- dimedιyledιoxy)carbonyl)-4-(N-medιyl-N-(3-(l-Methylethylamino-2-pyridinyl)amino)piperidine (PREPARATION 53) for l-(l,l-dimethylethoxy)carbonyl)-4-(N-methyl-N-(3-nitro-2- pyridinyl)amino)piperidine and starting the reaction at 0°, die title compound is obtained, NMR (d-methanol) 7.47, 6.89, 3.50, 3.05, 2.93, 2.52, 2.42, 1.62, 1.45 and 1.11 δ. PREPARATION 55 l -[5-Nitroindolyl-2-carbonyl]-4-[N-methyl-N-(3-(l - medιyledιylamino)-2-pyridinyl)amino]piperidine A mixture of 5-nitroindole-2-carboxylic acid (2.39 g) and l-(3-dimethylaminopropyl)-3- etiiylcarbodiimide hydrochloride (2.33 g) in dry THF (600 ml) are stirred widi a mechanical stirrer under nitrogen at 20-25° for 45 min. To this is added a solution of 4-(N-methyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino)-piperidine (PREPARAΗON 54, 2.88 g) in dry THF (20 ml) and die mixture is stirred for 1.8 days. The supernatant liquid is removed, concentrated to dryness, and diluted widi mediylene chloride (75 ml) and water (25 ml). The layers are separated and d e organic phase is washed widi saturated aqueous sodium bicarbonate (30 ml) and saline and dried over sodium sulfate. Removal of solvent under reduced pressure gives a solid which is chromatographed on silica gel (70-230 mesh, 400 g), eluting widi a gradient of methanol/chloroform (0.5/99.5 - 5/95). Pooling of the appropriate fractions, having an R f of about 0.34 by TLC (methanol/chloroform 5/95) and removal of solvent under reduced pressure gives die tide compound, mp 204-206°. PREPARAΗON 56 l-[5-Aminoindolyl-2-carbonyl]-4-[N-methyl-N-(3-(l- methyledιylamino)-2-pyridinyl)amino]-piperidine (VII) Palladium on carbon (10%, 200 mg) is added to a mixture of l-[5-nitroindolyl-2-carbonyl]- 4-[N-methyl-N-(3-(l-methyledιylamino)-2-pyridinyl)amino]pipfcridine (PREPARATION 55, 400 mg) in DMF/ methanol under nitrogen. The mixture is put under a hydrogen atmosphere (balloon), stirred for 5 hrs, and die catalyst is filtered off tiirough a pad of diatamacious earth. The filtrate is concentrated under reduced pressure to give the title compound. PREPARAΗON 57 1-Methyl 4-methoxy-α. azidocinnamate p-Methoxybenzaldehyde (5.0 g) and mediyl azidoacetate (16.9 g) are dissolved in 125 ml of methanol and cooled to -10° (ice-acetone bath). Then sodium medioxide (7.93 g, 25% in methanol) is added dropwise such that the temperature does not rise above -5°. After 2 hr die cooling bath is removed and die reaction is warmed to 20-25° while being monitored by TLC. When no starting material remained, die reaction is diluted widi etiier and saturated ammonium chloride. After extracting widi etiier die organic layers are washed widi ammonium chloride, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate is purified by flash column chromatography eluting widi ethyl acetate/hexane (1/99) to etiiyl acetate/hexane (10/90). The appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CDCI3) 7.80-7.76, 6.92-6.87, 3.88 and 3.79 δ. PREPARAΗON 58 Methyl 6-Methoxyindole-2-carboxylate Toluene (185 ml) is added to metiiyl 4-methoxy-α- azidocinnamate (PREPARAΗON 61, 7.73 g) and die reaction is brought to reflux and maintained at reflux for 3 hr. Then the reaction is concentrated under reduced pressure and triturated widi hexane. The solids are filtered and dried under reduced pressure to give the title indole, HRMS Calcd. for C 11 H 11 NO 3 : 205.0739, found: 205.0736; NMR (300 MHz, CDC1 3 ) 8.75, 7.47, 7.11, 6.76-6.73, 3.86, and 3.79 δ. PREPARAΗON 59 6-Methoxyindole-2-carboxylic acid (I) Methyl 6-methoxyindole-2-carboxylate (PREPARAΗON 62, 5.71 g) is dissolved in 70 ml of dioxane and 7 ml of water and 1.87 g of crushed potassium hydroxide are added. The reaction is heated to 50° and stirred 1.5 hr. The reaction mixture is acidified to pH 4-5 and extracted several times with methanol/chloroform (10/90). The organic layers are combined and dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give die title acid, NMR (300 MHz, d4-CD 3 OD) 7.47, 7.08, 6.90, 6.72 and 3.82 δ. PREPARAΗON 60 Methyl 4-nitro-o_-azidocinnamate Following the general procedure of PREPARAΗON 57 and making non-critical variations but starting with p-nitrobenzaldehyde (10 g) and metiiyl azidoacetate (30.4 g), the title compound is obtained, NMR 8.34, 8.07, 7.02, and 4.07 δ. PREPARAΗON 61 Methyl 6-nitroindole-2-carboxylate Following the general procedure of PREPARAΗON 58 and making non-critical variations but starting with methyl 4-nitro-α. azidocinnamate (PREPARAΗON 60, 6.75 g), the tide compound is obtained, NMR (300 MHz, CD 3 OD) 8.30, 7.87, 7.72, 7.18, and 3.86 δ. PREPARAΗON 62 6-Nitroindole-2-carboxylic acid (T) Following the general procedure of PREPARAΗON 59 and making non-critical variations but starting with methyl 6-nitroindole-2-carboxylate (PREPARAΗON 61), the title compound is obtained. PREPARAΗON 64 l-[6-Nitroindoyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyri- dinyl]piperazine Following the general procedure of PREP RAΗON 55 and making non-critical variations but starting with 6-nitroindole-2-carboxylic acid (PREPARAΗON 62) and l-[3-(l- methylethylamino)-2-pyridinyl]piperazine (PREPARAΗON 4), the title compound is obtained. PREPARAΗON 65 1 -[ 1 , 1 -Dimethylethoxycarbonyl]-4-[3-(l , l-dimethylprop-2-ynylamino)-2- pyridinyl]piperazine To a mixture of l-[l,l-dimedιyledιoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine (International Publication No. WO 88/08424, 5.40 g), cuprous chloride (1.00 g), copper powder (1.00 g), and dry dimethylformamide (25 ml) under nitrogen at 0° is added a solution of 3-chloro- 3-methyl-l-butyne (2.00 g) in dry dimediylfoπnamide (5 ml) in 4 portions over 15 min. The resulting mixture is then stirred at 20-25° for 16 hrs, concentrated, and diluted with methylene chloride (75 ml) and water (20 ml). The layers are separated and the aqueous phase is extracted widi mediylene chloride (25 ml). The combined organic phase is washed with saline (20 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a residue which is chromatographed on silica gel (70-230 mesh, 500 g), eluting widi a gradient of etiiyl acetate/hexane (10/90-20/80). Pooling of fractions giving an R f = 0.31 (ethyl acetate/hexane, 25/75) and removal of solvent under reduced pressure gives die tide compound, NMR (CDC1 3 ) 7.75, 7.47, 6.94, 4.61, 3.56, 3.00, 2.39, 1.64 and 1.48 δ. PREPARAΗON 66 l-[l,l-Dimethylethoxycarbonyl]-4-[3-(l,l-dimethylpropylamino)-2- pyridinyl]piperazine To a solution of l-[l,l-dimetiιyledιoxycarbonyl]-4-[3-(l,l-dimethylprop-2-ynylamino)-2- pyridinyl]piper___ine (PREPARAΗON 65, 1.00 g) in absolute ethanol (20 ml) under nitrogen is added wet Raney Nickel (650 mg). The mixture is put under a hydrogen atmosphere at 40 psi (Parr) for 20 hr, filtered through a pad of celite, and concentrated. The residue is then taken up in mediylene chloride (40 ml), washed widi saline (10 ml), dried over sodium sulfate, and concentrated under reduced pressure to give the title compound, NMR (CDC1 3 ) 7.64, 7.03, 6.85, 4.56, 3.56, 2.97, 1.71, 1.48, 1.33 and 0.88. PREPARAΗON 67 l-[5-Nitroindole-2-carbonyl]-4-[3-(l,l-dimethylpropylamino)-2- pyridinyl]piperazine To a solution of l-[l,l-dimethyle_hoxycarbonyl]-4-[3-(l,l-dimethylpropylamino)-2- pyridinyl]piperazine (PREPARAΗON 66, 4.99 g) in methylene chloride (75 ml) under nitrogen at 0° is added trifluoroacetic acid (14.3 ml) over 1 min. The resulting mixture is warmed to 20- 25°, stirred for 15 hrs, and tiien added to a solution of sodium hydroxide (7.44 g) in water (175 ml) at 0°. The layers are separated, d e aqueous phase is extracted with methylene chloride (3 x 70ml), and the combined organic layer is washed with saline (60 ml), dried over sodium sulfate, and concentrated under reduced pressure to give the unprotected intermediate (Rf = 0.14, TLC, methanol/chloroform, 10/90). In a flame-dried flask under nitrogen, 5-nitroindole-2-carboxylic acid (2.13 g) and l.l'-carbonyldiimidazole (1.75 g) are dissolved in dry tetrahydrofuran and stirred for 3 hrs at 20-25°. Then a solution of the intermediate (2.57 g) in dry tetrahydrofuran (3ml) is added and die resulting mixture is stirred for 1.8 days. The reaction mixture is filtered to give the title compound, NMR (dimethylsulfoxide-dg) 12.41, 8.65, 8.09, 7.58, 7.16, 7.11, 6.91, 4.57, 3.93, 3.00, 1.71, 1.31 and 0.84. The filtrate is concentrated and is triturated widi cold metiianol to give an additional amount of die title compound. PREPARAΗON 68 l-(l,l-Dimethyled oxycarbonyl)-4-(l,l-dimedιylprop-2-ynyl)piperazine To a mixture of l-(l,l-dimethylethoxycarbonyl)piperazine (3.29 g), copper powder (20 mg), cuprous chloride (20 mg), ether (4 ml), and water (1 ml) under nitrogen at 0° is added a solution of 3-chloro-3-methyl-l-buty_e in ether (1 ml) in 4 portions over 15 min. The mixture is stirred at 20-25° for 2 hr, diluted with ether (25 ml) and water (10 ml), and the layers are separated. The aqueous layer is extracted widi etiier (3 x 25ml), and die combined organic layer is washed widi saline (25 ml), dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give a solid which is then chromatographed on silica gel (70-230, 100 g), eluting with ethyl acetate/hexane (25/75). Pooling of fractions giving an R f = 0.48 by TLC (ethyl acetate/hexane, 50/50) and removal of solvent under reduced pressure gives die tide compound, mp 105.5-107°. PREPARAΗON 69 l-(l,l-Dimethyledιoxycarbonyl)-4-(l,l-dimethylpropyl)piper___ine A flask is charged witii platinum oxide (250 mg) and absolute etiianol (20 ml) and is stirred under a hydrogen atmosphere (balloon) for 1 hr. Then a solution of 1-(1,1- dimethyletiιoxycarbonyl)-4-(l,l-dimethylprop-2-ynyl)piperazine (PREPARAΗON 68, 1.77 g) in absolute ethanol (20 ml) is added, and the mixture is stirred under hydrogen (balloon) for 4 hr, filtered, and concentrated. The residue is chromatographed on silica gel (70-230 mesh, 80 g), eluting widi etiiyl acetate/hexane (25/75), and the appropriate fractions (Rf = 0.32, TLC, ethyl acetate/hexane, 25/75) are pooled and concentrated to give the title compound, NMR (CDC1 3 ) 3.38, 2.46, 1.46-1.38, 0.97 and 0.84. PREPARAΗON 70 l-(l,l-Dimethylp_opyl)piperazine Following the general procedure of PREPARAΗON 50, but substituting 1-(1,1- dimethylethoxycarbonyl)-4-(l,l-d_methylpropyl)piperazine (PREPARAΗON 69) for 1-[1,1- dimetiiyledioxycarbonyl]^-[N-m_thyl-N-(3-nitro-2-pyridinyl)amino]]piperidine and starting the reaction at 0°, the title compound is obtained, NMR (CDC1 3 ) 2.87, 2.50, 1.91, 1.42, 0.97 and 0.84. PREPARAΗON 71 l-[ 1 , 1 -Dimethylethoxycarbonyl]-4-[N-methyl-N-(3-(l , 1 -dimethylprop-2- ynyl_mino)-2-pyridinyl)amino]piperidine Following the general procedure of EXAMPLE 65, but substituting 1-[1,1- dimedιyletiιoxycarbonyl]-4-[N-methyl-N-(3-amino-2-pyridinyl)amino]piperidine(PREPARAΗON 52) for l-[l,l-dimethylethoxycarbonyl]-4-[3-amino-2-pyridinyl]piperazine and working up die reaction after 2 hrs, the title compound is obtained, NMR (CDC1 3 ) 7.79, 7.51, 6.95, 4.92, 4.05, 3.19, 2.75, 2.61, 2.38, 1.75, 1.62, 1.49 and 1.45 δ. PREPARAΗON 72 1 -[ 1 , l -Dim ethylethoxycarbonyl]-4-[N-methyl-N-(3-( l , 1 - dimediylpropylamino)-2-pyridinyl)amino]piperidine Following the general procedure of EXAMPLE 66, but substituting 1-[1,1- dimethylethoxycarbonyl]-4-[N-methyl-N-(3-(l , l -dimethylprop-2-ynylamino)-2- pyridinyl)amino]piperidine (PREPARAΗON 71) for l-[l,l-dimethylethoxycarbonyl]-4-[3-(l,l- dimed ylprop-2-ynylamino)-2-pyridinyl]piperazine, the crude product is obtained. This is then chromatographed on silica gel (70-230 mesh, 250 g), eluting widi a gradient of ethyl acetate/hexane (10/90-35/65), and die appropriate fractions are pooled and concentrated to give the tide compound, NMR (CDC1 3 ) 7.67, 7.04, 6.87, 4.87, 4.04, 3.20, 2.76, 2.61, 1.71, 1.50, 1.45, 1.31 and 0.86 δ. PREPARAΗON 73 4-[N-Methyl-N-(3-(l , l-dimedιylpropylamino)-2-pyridinyl)amino]piperidine Following the general procedure of PREPARAΗON 50, but substituting 1-[1,1- dimethyletiιoxyca_:bonyl]-4-[N-methyl-N-(3-(l,l-dimetiιylpropyl_m (PREPARATION 72) for l-[l,l-dimethylethoxycarbonyl]-4-[N-methyl-N-(3-nitro-2- pyridinyl)amino]piperidi_e, starting the reaction at 0°, and working up the reaction after 1.5 hr, the title compound is obtained, NMR (CDCI3) 7.66, 7.02, 6.84, 4.86, 3.39, 3.13, 2.63, 1.81-1.52, 1.31 and 0.87 δ. PREPARAΗON 74 l-[5-Nitroindole-2-carbonyl]-4-[N-methyl-N-(3-(l , 1-dimethylpropylamino)- 2-pyridinyl)amino]piperidine Under nitrogen 5-nitroindole-2-carboxylic acid (977 mg) and 1 , 1 '-carbonyldiimidazole (807 mg) are dissolved in dry tetrahydrofuran (25 ml) and die mixture is stirred at 20-25° for 2 hr. A solution of 4-[N-methyl-N-(3-(l, l-dimethylpropylamino)-2-pyridinyl)amino]piperidine (PREPARAΗON 73, 1.31 g) in dry tetrahydrofuran is tiien added, and the resulting mixture is stirred for 18 hr and filtered. The filtrate is concentrated, diluted witii mediylene chloride (75 ml), washed witii water and saline (20 ml), dried over sodium sulfate, and concentrated under reduced pressure to give a solid which is chrc-aiatographed on silica gel (70-230 mesh, 200 g), eluting with a gradient of ethyl acetate/hexane (50/50-90/10). Pooling of fractions giving an R f = 0.08 by TLC (ethyl acetate hexane, 50/50) and removal of solvent under reduced pressure gives die tide compound, mp 205.5-207.5°. PREPARAΗON 75 1 - [5-Am ino indol e-2-carbonyl]-4-[N-methyl-N-(3-( l , 1 - dimethylpropylamino)-2-pyridinyl)amino]piperidine Following the general procedure of EXAMPLE 41, but substituting l-[5 __itroindole-2- carbonyl]-4-[N-methyl-N-(3-(l, l-dimethylpropylamino)-2-pyridinyl)amino]piperidine (PREPARAΗON 74) for l-[5-nitroindole-2-carbonyl]-4-[3-(l,l-dimethylpropylamino)-2- pyridinyl]piperazine and using dimediylformamide/methanol (25/75) as solvent, the title compound is obtained, NMR (CDC1 3 ) 9.95, 7.69, 7.20, 7.05, 6.88, 6.71, 6.55, 4.91, 4.64, 3.86, 3.40, 3.11, 2.62, 1.91, 1.63, 1.31 and 0.86 δ. PREPARAΗON 76 l-(l,l-Dimethyled oxycarbonyl)-cis-3,5-dimethylpiperazine Di-tert-butyldicarbonate (5.42 g) in dry methylene chloride (20 ml) is added to a solution of cis-2,6-dimedιylpiperazine in dry methylene chloride (70 ml) over one hour. The mixture is stirred an additional 30 min, washed widi water and saline, dried over sodium sulfate and concentrated to yield die titie compound, NMR (chloroform-d) 3.95, 2.77, 2.32, 1.46, 1.06 δ. PREPARAΗON 77 cis 3,4,5-Trimetiιylpiperazine To a solution of l-(l,l,dimethylethoxycarbonyl)-cis-3,5-dimethylpiperazine (PREPARAΗON 76, 4.28 g) in dioxane (100 ml) is added IM sodium dihydrogen phosphite (100 ml, made by mixing equal volumes of 2M sodium hydroxide and 2M phosphorous acid) followed by die addition of formalin solution (37%, 16 ml). The mixture is heated at 65° for 2.5 hr and extracted with methylene chloride. The organic phase is washed witii water and saline, dried over sodium sulfate and concentrated to ca. 50 ml. The remaining methylene chloride and dioxane are removed by distillation leaving 4.3 g of residue in the distillation flask. This material is dissolved in methylene chloride (40 ml), cooled to 0°, and trifluoroacetic acid (14.5 ml) is added. The mixture is stirred for 1.25 hr and sodium hydroxide (11.3 g) in water (30 ml) is added. The phases are separated and die aqueous phase is extracted with additional mediylene chloride. The total combined organics are dried over magnesium sulfate and concentrated by distillation to give a mixture of the titie compound and residual starting material. On standing die mixture partially crystallizes. Filtration and washing widi ediyl ether gives the titie compound, NMR (chloroform-d) 3.09, 2.67, 2.39, 1.16 δ. PREPARAΗON 78 4-(2-(2-Methoxyetiιoxy)ethoxy)benzaldehyde Following the general procedure of EXAMPLE 1, and making non-critical variations but substitutingl-bromo-2-(2-methoxyethoxy)etiiane(Aldrich)for2-[2-(2-chloroethoxy)edioxy]ethanol, the titie compound is obtained, mp 44^.7°; NMR (300 MHz, CDC1 3 ) 9.78, 7.72, 6.92, 4.12, 3.79, 3.63, 3.48, 3.29 δ. PREPARAΗON 79 Methyl 4-(2-(2-metiιoxyedιoxy)etiιoxy)-Q. azidocinnamate Following the general procedure of EXAMPLE 2, and making non-critical variations but substituting 4-(2-(2-methoxyethoxy)ethoxy)benzaIdehyde (PREPARAΗON 78) for 4-[(2-(2-hydroxyethoxy)ethoxy)ethoxy]benzaldehyde, the titie compound is obtained, NMR (300 MHz, CD 3 OD) 7.68, 6.85, 6.78, 4.05, 3.78, 3.72, 3.61, 3.48, 3.28 δ. PREPARAΗON 80 Methyl 6-(2-(2-methoxyethoxy)ethoxy)indole-2-carboxylate Following the general procedure of EXAMPLE 3, and making non-critical variations but substituting 4-(2-(2-methoxyethoxy)ethoxy> __-azidocinnamate (PREPARAΗON 79) for 4-[(2-(2-hydroxyeώoxy)ethoxy)ethoxy]-α-azidoci__amate, the titie compound is obtained, NMR (300 MHz, CD 3 OD) 7.59, 7.20, 7.02, 6.87, 4.25, 4.00, 3.96, 3.80, 3.67 and 3.47. PREPARAΗON 81 6-(2-(2-Medιoxyedιoxy)ethoxy)indole-2-carboxylic acid Following die general procedure of EXAMPLE 4, and making non-critical variations but substituting methyl 6-(2-(2-methoxyetiιoxy)ethoxy)indole-2-carboxylate (PREPARAΗON 79) for methyl 6-[(2-(2-hydroxyedιoxy)ethoxy)ethoxy]indole-2-carboxylate, the title compound is obtained, mp 99-102°. PREPARAΗON 82 Ethyl 5-[(3-chloropropyl)sulfonamido]indole-2-carboxylate Ethyl 5-aminoindole-2-carboxylate (2.0 g) and pyridine (0.82 ml) are dissolved in 15 ml of methylene chloride and 10 ml of THF. Then the reaction is cooled to 0° and 3-chloropropanesulfonyl chloride (1.25 ml) is added and die reaction is allowed to slowly warm to 20-25° and stir for 16 hr. Then the reaction is diluted with chloroform, washed widi saturated aqueous sodium bicarbonate and saline. The organic layers are dried over anhydrous sodium sulfate and concentrated under reduced pressure. The product is dissolved in ethyl acetate and filtered dirough a plug of silica gel and crystallized from methanol, mp 195-196°. PREPARAΗON 83 Ethyl 5-[(3-(piperadin-l-yl)propyl)sulfonamido]indole-2-carboxylate Ethyl 5-[(3-chloropropyl)sulfonamido]indole-2-carboxylate (PREPARAΗON 82, 2.3 g) is dissolved in acetonitrile (10 ml) and piperadine (27 ml). Solid sodium iodide (1.0 g) is added and the reaction is stirred overnight at 20-25°. The reaction is diluted witii methylene chloride, washed widi saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography, eluting widi a gradient of 5% metiianol/mediylene chloride to 10 % methanol/methylene chloride, pooling and concentration of the appropriate fractions gives the title compound, NMR (300 MHz, d 4 -CD 3 OD) 7.45, 7.32, 7.12, 7.03, 4.28, 2.96, 2.28, 1.18, 1.42, 1.33 and 1.30. PREPARAΗON 84 5-[(3-(Piperadin-l-yl)propyl)sulfonamido]indole-2-carboxylic acid Ethyl5-[(3-φiperadin-l-yl)propyl)sulfonamido]indole-2-carboxylate(PREPARAΗON 83, 1.63 g) is dissolved in 10 ml of dioxane and 5 ml of water. Then 0.59 g of solid potassium hydroxide pellets are added and die reaction is stirred at 20-25° for 24 hr. Then 8.91 ml of IN hydrochloric acid is added after diluting die reaction with 100 ml of water. The mixture is extracted wid n-butanol (3 X 50 ml) and die organic layer is separated and evaporated under reduced pressure to provide the titie compound, NMR (300 MHz, dg-DMSO) 7.37, 7.27, 7.00, 6.90, 2.91, 2.25, 1.75, 1.31, (peak at 4.3 ppm obscured by DMSO). PREPARAΗON 85 l-[5-((l ^bobenzyloxy)piperad_n-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l - medιyledιylamino)-2-pyridinyl]piperazine l-[5-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 7, 0.5 g) and l-benzyloxycarbonylpiperadine-4-carboxylic acid (0.36 g) is dissolved in 2.6 ml of DMF and 0.278 g of EDC is added. The reaction is stirred at 20-25° overnight, diluted widi chloroform, extracted witii saturated aqueous sodium bicarbonate, water, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography, eluting with methanol/chloroform (2.5/97.5), pooling and concentrating the appropriate fractions gives the title compound, mp 138-142°, NMR (300 MHz, CD 3 OD) 8.05, 7.72, 7.55-7.40, 7.14, 6.97, 5.28, 4.38, 4.18, 3.79, 3.45, 3.25, 3.02, 2.76, 2.05, 1.86, 1.40. PREPARAΗON 86 l-[5-(3-Chloropropyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine l-[5-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 7, 2.0 g) is dissolved in 17.6 ml of pyridine and cooled to 0°. Then 3-chloropropanesulfonyl chloride (1.28 ml) is added and die reaction is allowed to warm to 20-25° and stirred 8 hr. The reaction is diluted widi chloroform, washed widi saturated aqueous sodium bicarbonate, water, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with a gradient of 50/50 ethyl acetate/hexane to 100% ethyl acetate, pooling and concentrating of the appropriate fractions gives the titie compound, mp 219-221°. PREPARAΗON 87 3-Medιoxy-4-[2-(l-morpholinyl)benzaldehyde Vanillin (10.0 g) and 4-(2-chloroethyl)morpholine hydrochloride (19.56 g) are dissolved in 219 ml of DMF and solid potassium carbonate (29 g) is added. The reaction is refluxed for 24 hr, cooled to 20-25° and the DMF is removed under reduced pressure. The remainder of die reaction is dissolved in ethyl acetate and washed widi IN aqueous sodium hydroxide, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting witii methanol/etiiyl acetate (2/98),pooling and concentrating the appropriate fractions gives the title compound, NMR (300 MHz, CDC1 3 ) 9.76, 7.36, 7.34, 6.93, 4.26, 3.84, 3.73, 2.92, 2.66. PREPARAΗON 88 Methyl 3-methoxy-4-[2-(l-morpholinyl)ethoxy]-α-azidocinnamate (IV) Following die general procedure of EXAMPLE 2, and making non-critical variations but substituting 3-methoxy-4-[2-(l-morpholinyl)benzaldehyde (PREPARAΗON 87) for 4-[(2-(2- hydroxyetiιoxy)ethoxy)ethoxy]benzaldehyde, the titie compound is obtained, NMR (300 MHz, CDC1 3 ) 7.29, 7.11, 6.67, 6.65, 4.05, 3.67, 3.58, 2.75, 2.51. PREPARAΗON 89 Methyl 5-methoxy-6-[2-(l-morpholinyl)ethoxy]-indole-2-carboxylate (V) Following the general procedure of EXAMPLE 3, and making non-critical variations but substi tingmemyl3-memoxy-4-[2-(l-morpholinyl)etiιoxy]-α-azidocinnamate(PREPARAΗON88) for methyl 6-[(2-(2- hydroxy__hoxy)ethoxy)ethoxy]-α-azidocinnamate and toluene for xylene, the title compound is obtained, mp 123-124°, NMR (300 MHz, CD 3 OD) 6.99, 6.96, 6.85, 4.06, 3.78, 3.74, 3.61, 2.74, 2.54. PREPARAΗON 90 5-Methoxy-6-[2-(l-morpholinyl)ethoxy]indole-2-carboxylic acid (VI) Following the general procedure of EXAMPLE 4, and making non-critical variations but substituting methyl 5-me_hoxy-6-[2-(l-mo_pholinyl)ethoxy]indole-2-carboxylate (PREPARAΗON 89) for methyl 6-[(2-(2-hydroxyetiιoxy)ethoxy)etiιoxy]indole- 2-carboxylate, the title compound is obtained, mp > 350°' but turned black at 237°; NMR (300 MHz, CD 3 OD) 7.48, 7.03, 6.90, 6.70, 4.09, 3.95, 3.75, 3.62, 3.54, 3.00, 2.76, 2.56, 1.16; CMR (75 MHz, CD 3 OD) 165.2, 151.4, 149.6, 147.8, 138.7, 135.4, 133.1, 129.4, 122.4, 122.1, 118.9, 105.9, 104.5, 97.7, 68.4, 67.8, 58.9, 57.8, 55.4 50.6, 45.0, 23.0 δ. PREPARAΗON 91 4-[2-(l-Piperadinyl)ethoxy]benzaldehyde 4-Hydroxybenzaldehyde (25.0 g) and 4-(2-chloroethyl)piperadine hydrochloride (60.38 g) are dissolved in 650 ml of DMF and solid potassium carbonate (45 g) is added. The reaction is refluxed for 24 hr, cooled to 20-25° and die DMF is removed under reduced pressure. The remainder of the reaction is dissolved in chloroform and washed widi IN aqueous sodium hydroxide, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with a gradient of 50% etiiyl acetate/hexane to 5% methanol/ethyl acetate, pooling and concentrating the appropriate fractions gives the tide compound, NMR (300 MHz, CDCI3) 9.75, 7.69, 6.87(d, J = 8.7 Hz, 2H), 4.10(t, J = 5.8 Hz, 2H), 2.73(t, J = 5.8 Hz, 1H), 2.45(m, 4H), 1.52(m, 4H), 1.36(m, 2H) δ. PREPARAΗON 92 Methyl 4-[2-(l-piperadinyl)ethoxy]-c.-azidocinnamate (IV) Following the general procedure of EXAMPLE 2, and making non-critical variations but substituting 4-[2-(l-piperadinyl)benzaldehyde (PREPARAΗON 91) for 4-[(2-(2-hydroxyethoxy)- ethoxy)ethoxy]benzaldehyde, the titie compound is obtained, NMR (300 MHz, CDC13) 7.75(d, J = 8.8 Hz, 2H), 6.89(m, 2H), 6.85(s, 1H), 4.16(t, J = 5.9 Hz, 2H), 3.87(s, 3H), 2.82(t, J = 5.9 Hz, 2H), 2.56(br, 4H), 1.63(m, 4H), 1.45(m, 2H) δ. PREPARAΗON 93 Methyl 6-[2-(l-piperadinyl)ethoxy]indole-2-carboxylate (V) Following the general procedure of EXAMPLE 3, and making non-critical variations but substituting methyl 4-[2-(l-piperadinyl)ethoxy]-α-azidocinnamate (PREPARAΗON 92) for methyl 6-[(2-(2-hydroxyethoxy)ethoxy)edιoxy]-α-azidocinnamate, die title compound is obtained, NMR (300 MHz, CD3OD) 7.40(d, J = 8.8 Hz, 1H), 7.00(d, J = 0.8 Hz, 1H), 6.81(m, 1H), 6.65(dd, J = 2.2, 8.8 Hz, 1H), 4.05(t, J = 5.7 Hz, 2H), 3.79(s, 3H), 2.71(t, J = 5.7 Hz, 2H), 2.48(m, 4H), 1.53(m, 4H), 1.39(m, 2H). PREPARAΗON 94 6-[2-(l-Piperadinyl)etiιoxy]indole-2-carboxylic acid (VI) Following the general procedure of EXAMPLE 4, and making non-critical variations but substituting methyl 6-[2-(l-piperadinyl)ethoxy]indole-2-carboxylate (PREPARAΗON 93) for methyl 6-[(2-(2-hydroxyethoxy)ethoxy)ethoxy]indole-2-caιboxylate, the title compound is obtained, NMR (300 MHz, CD 3 OD) 7.40(m, 1H), 6.96(br, 1H), 6.88(br, 1H), 6.70(m, 1H), 4.28(br, 2H), 3.20(br, 2H), 3.18(br, 4H), 1.78(br, 4H), 1.58(m, 1H), 1.65(m, 1H). PREPARAΗON 95 l-Benzyl-4-[3-(l-cyano-l-me_ιylethylamino)pyridyl]piperazine The l-[5-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 7, 11.68 g, 43.51 mmol) is dissolved in 130 ml methanol and 130 ml acetic acid. Acetone (25.6 ml, 348.1 mmol) and trimethylsilylcyanide (46.4 ml, 348.1 mmol) are added and die mixture is stirred twenty hours. The solution is poured into cold aqueous sodium hydroxide solution, stirring vigorously, to give a basic solution. The aqueous solution is then extracted with ethyl acetate, the organic extract is washed witii saline, dried over sodium sulfate and evaporated to dryness to give an oily residue of 12.6 g. Chromatography on a 400 g silica gel column with a step gradient of etiiyl acetate/hexane (2/3 to 3/2, v/v), pooling and concentrating die appropriate fractions gives the title compound, NMR (300 MHz, CD 3 OD) 7.65 (m, 1 H), 7.29-7.17 (m, 6 H), 6.96-6.92 (m, 1 H), 3.51 (s, 2 H), 2.98 (t, 4 H, J=5 Hz), 2.55 (bs, 4 H), 1.14 (s, 6 H). PREPARAΗON 96 l-Benzyl-4-[3-(l,l-dimediyletiiylamino)pyridyl]piperazine Methyllithium (61 ml, 85 mmol) as a 1.4M solution in diethyl ether is added to 30 ml tetrahydrofuran and cooled to -78°. l-Benzyl-4-[3-(l-cyano-l-methylethylamino)pyridyl]- piperazine (PREPARAΗON 95, 7.14 g, 21.28 mmol), dissolved in 30 ml cooled tetrahydrofuran, is cannulated into the methyllithium solution, rinsing in with 10 ml THF. The reaction is stirred at -78° and allowed to warm to 20-25° overnight. The reaction is cautiously quenched widi water, tiien extracted from water with methylene chloride. The extract is dried over sodium sulfate and concentrated. The concentrate is chromatographed on a 500 g silica gel column, eluting with ethyl acetate/hexane (2/3, v/v), the appropriate fractions are pooled and concentrated to give the title compound, NMR (300 MHz, CD 3 OD) 7.44 (m, 1 H), 7.43-7.07 (m, 6 H), 6.84-6.80 (m, 1 H), 3.49 (s, 2 H), 2.92 (t, 4 H, J=5 Hz), 2.52 (bs, 4 H), 1.28 (s, 9H). PREPARAΗON 97 l-[3-(l,l-Dimethyledιylamino)pyridyl]piperazine l-Benzyl^-[3-(l,l-dimethylethylamino)pyridyl]piperazine (PREPARATION 96, 4.25 g, 13.10 mmol) is dissolved in 100 ml edianol. Palladium (10% on carbon, 1.0 g) is added and die solution hydrogenated at 40 psi hydrogen gas. The mixture is filtered and concentrated to give the titie compound, NMR (300 MHz, CD 3 OD) 7.53 (dd, 1 H, J=1.5, 5 Hz), 7.19 (dd, 1 H, J= 1.5, 8 Hz), 6.93 (dd, 1 H, J=5, 8 Hz), 2.95 (s, 8 H), 1.39 (s, 9 H). PREPARAΗON 98 l-[5-Nitroindolyl-2-carbonyl]-4-[3-(l , l-dimethylediylamino)-2-pyridyl]- piperazine Following the general procedure of EXAMPLE 6, and making non-critical variations but substituting l-[3-(l,l-dimetiιylethylamino)-2-pyridyl]piperazine (PREPARAΗON 97) for l-[3-(l-methylethylamino)-2-pyridinyl]piperazine, the titie compound is obtained, mp 278° (dec.). PREPARAΗON 99 l-[5-Aminoindolyl-2-carbonyl]-4-[3-(l , l-dimethyledιylamino)-2-pyridyl]- piperazine Following the general procedure of EXAMPLE 7, and making non-critical variations but substituting l-[5-nitroindolyl-2-carbonyl]-4-[3-(l , l-dimediylediylamino)-2-pyridyI]piperazine (PREPARAΗON 98) for l-[5-nitroindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridyl]- piperazine, the titie compound is obtained, NMR(CDC1 3 ) 7.49, 7.16, 6.89, 6.79, 6.71, 6.62, 3.93, 2.97, 1.34 δ. PREPARAΗON 100 Ethyl 5-(4-metiiylpiperazin-l-ylcarbonylamino)indole-2-carboxylate Following the general procedure of EXAMPLE 20 and making non-critical variations but substituting methyl 5-aminoindole-2-carboxylate for l-[5-aminoindolyl-2-carbonyl]-4-[3-(l- methyledιylamino)-2-pyridinyl]piperazine, the titie compound is obtained, NMR(CDC1 3 ) 7.62, 7.48, 7.22, 7.18, 7.08, 6.97, 6.75, 4.36, 3.49, 2.39, 2.28, 1.38 δ. PREPARAΗON 101 5-(4-Methylpiperazin-l-ylcarbonylamino)indole-2-carboxylic acid Following the general procedure of PREPARAΗON 84 and making non-critical variations but substituting ethyl 5-(4-methylpiperazin-l-ylcarbonylamino)indole-2-carboxylate (PREPARAΗON 100) for ethyl 5-[(3-(piperadin-l-yl)propyl)sulfonamido]indole-2-carboxylate,the title compound is obtained, NMR(CD 3 OD) 7.70, 7.46, 7.32, 7.10, 7.05, 6.87, 3.54, 2.48, 2.32 δ. EXAMPLE 1 4-[2-(2-(2-Hydroxyethoxy)ethoxy)ethoxy]benzaldehyde (III) 4-Hydroxybenzaldehyde (II, lO.Og) is dissolved in DMF (198 ml) and cooled to 0°, sodium hydride (60% in mineral oil, 3.44 g) is added, after bubbling ceased (15-20 min), 2-[2-(2- chloroethoxy)ethoxy]ethanol (17.8 ml) and sodium iodide (0.61 g) is added. The reaction is stirred at 20-25° for 0.5 hours and heated to reflux for 78 hours. The reaction is poured into water and washed with ethyl acetate (3 x). The phases are separated and die organic layer is washed with water, saline and concentrated under reduced pressure with heat. The material is purified witii flash column chromatography, eluting with ethyl acetate/hexane (50/50) to (75/25). The appropriate fractions are pooled and concentrated to give the title compound, MS tiieory: 254.1154. Found: 254.1163. EXAMPLE 2 Mediyl 4-[(2-(2-hydroxyedιoxy)ethoxy)edιoxy]-α-azidocinnamate (IV) 4-[2-(2-(2-Hydroxyethoxy)ethoxy)edιoxy]benzaldehyde (HI, EXAMPLE 1, 17.3 g) and a- azidometiiyl acetate (31.3 g) are dissolved in metiianol (136 ml) and cooled to -10°. Sodium medioxide in methanol (25 %, 77.7 ml) is added dropwise. The reaction is warmed to 20-25° until TLC indicates die reaction is complete. The reaction mixture is poured into water and extracted witii ethyl acetate. The phases are separated and die organic phase is concentrated and purified by flash column chromatography to give the title compound. EXAMPLE 3 Methyl 6-[(2-(2-hydroxyethoxy)ethoxy)ethoxy]indole-2- carboxylate (V) Met! 1 4-[(2-(2-hydroxyethoxy)ethoxy)ethoxy]-α-azidoc_nn_mate (IV, EXAMPLE 2, 3.0 g) is dissolved in xylene (86 ml) and quickly heated to reflux. TLC indicates disappearance of starting material, the reaction is cooled to 20-25° and die material is purified by flash column chromatography eluting with ethyl acetate/hexane (75/25). The appropriate fractions are pooled and concentrated to give the titie compound, MS ώeory: 323.1369. Found: 323.1366. EXAMPLE 4 6-[(2-(2-hydroxyethoxy)ethoxy)ethoxy]indole-2-carboxylic acid (VI) Methyl 6-[(2-(2-hydroxyethoxy)ethoxy)ethoxy]indole-2-carboxylate (V, EXAMPLE 3, 2.9 g) and potassium hydroxide (1.0 g) are dissolved in dioxane (25 ml) and water (5 ml). The reaction is warmed to 50° for 3 hours. The reaction is neutralized by the addition of hydrochloric acid (IN, 17 ml), extracted with TΗF/chloroform (50/50, 3 x), washed widi saline and concentrated under reduced pressure witii heat. The material is purified by flash column chromatography eluting with methanol/chloroform/acetic acid (5/94/1). The appropriate fractions are pooled and concentrated to give d e title compound, MS theory: 309.1212. Found: 309.1208. EXAMPLE 5 l-[6-(2-(2-Hydroxyethoxy)ethoxy)ethoxyindolyl-2-carbonyl]-4-[3-(l- me_hylethylamino)-2-pyridinyl]piper___ine (I) 6-[(2-(2-Hydroxyethoxy)ed oxy)ethoxy]indole-2-carboxylic acid (VI, EXAMPLE 4, 0.20 g) and 3-(l-metiιyledιylamino)-2-pyridinyl]piperazine (0.157 g) is dissolved in THF (4 ml) and l-(ethyl)-3-(dimethylaminopropyl)carbodiimide (0.16 g) is added. The reaction is stirred at 20-25° for 2.75 hours, poured into chloroform, washed widi saturated sodium bicarbonate and saline. The material is concentrated under reduced pressure witii heat and purified by flash column chromatography eluting with methanol/chloroform (5/95). The appropriate fractions are pooled and concentrated to give die titie compound, mp 157-159°. EXAMPLE 6 l-[5-Nitroindolyl-2-carbonyl]-4-[3-(l-methyledιylamino)-2- pyridinyl]piperazine l-(Edιyl)-3-(d_nethylaminopropyl)carbodiimide (0.45 g) is added to a solution of l-[3-(l-methylethyl)amino)-2-pyridinyl]piperazine (PREPARATION 4, 0.43 g) and 5-nitroindole-2-carboxylic acid (0.86 g) in THF (5 ml). The reaction is stirred at 20-25° for 3 hr, then it is dissolved in chloroform (50 ml) and extracted widi saturated aqueous sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography (200 g silica) eluting with ethyl acetate/hexane (50/50), the appropriate fractions are pooled and concentrated to give the title compound, mp 153-154°. EXAMPLE 7 l-[5-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine (VII) l-[5-Nitroindolyl-2-<__bonyl]^[3-(l-medιyl__ yl_mi__3 2^yridinyl]pipCT_zine (EXAMPLE 6, 1.0 g) is dissolved in edianol (60 ml) and THF (60 ml) and palladium on carbon (10%, 0.15 g) is added. The reaction is hydrogenated at 40 psi for 14 hr, then filtered dirough celite and concentrated under reduced pressure. Purification by flash chromatography, eluting witii ethyl acetate/hexane (50/50 — ► 75/25), pooling and concentrating the appropriate fractions gives the titie compound, mp 212-214°. EXAMPLE 8 l-[5-Edιylenesulfonamidoindolyl-2-carbonyl]-4-[3-(l-medιylethylamino)-2- pyridinyl]piperazine (IX) l-[(5-Aminoindolyl-2-carbonyl]-4-[3-(l-metiιyledιylamino)-2-pyridinyl]piperazine (V, EXAMPLE 7, 250 mg) is dissolved in pyridine (2 ml) and cooled to 0°. Then 2-chloroethane- sulfonyl chloride (VIII, 0.138 ml) is added dropwise. The reaction is warmed to 20-25° and stirred for 3 hours. The reaction mixture is poured into aqueous saturated sodium bicarbonate and extracted widi mediylene chloride. The phases are separated and die organic layer is dried over anhydrous sodium sulfate and concentrated under reduced pressure widi heat. Purification by flash column chromatography eluting with ethyl acetate/hexane (80/20). The appropriate fractions are pooled and concentrated to give die title compound, MS. m/e: 468, 453, 249, 219, 1922, 177 and 164. EXAMPLE 9 l-[5-(2-(l-PyrroIidino)ethyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) l-[5-Ethylenesulfonamidoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]- piperazine (DC, EXAMPLE 8, 173 mg), pyrrolidine (0.10 ml) and a catalytic amount of copper powder are refluxed togedier in xylene (5 ml) for 3.5 hours. The reaction is filtered through a pad of celite washing widi ethyl acetate and metiianol. After concentration under reduced pressure widi heat, the product is purified by flash column chromatography eluting with methanol/chloroform (10/90). The appropriate fractions are pooled and concentrated to give die title compound which is crystallized from aqueous ethanol, mp 145-146°. EXAMPLE 10 4-[2-(2-hydroxyetiιoxy)ethoxy]benzaldehyde (ffl) Following die general procedure of EXAMPLE 1, and making non-critical variations but substituting 2-[2-chloroetiιoxy]ethanol for 2-[2-(2-chloroethoxy)ethoxy]ethanol, the titie compound is obtained, NMR (CDC1 3 ) 7.82, 7.01, 4.21, 3.89, 3.76 and 3.66 δ. EXAMPLE 11 Metiiyl 4-[2-(2-hydroxyetiιoxy)etfιoxy]-c_-azidocinnamate (TV) Following the general procedure of EXAMPLE 2, and making non-critical variations but but substituting 4-[2-(2-hydroxyethoxy)ethoxy]benzaldehyde (HI, EXAMPLE 10) for 4-[2-(2-(2- hydroxyedιoxy)edιoxy)etiιoxy]benzaldehyde (EXAMPLE I), the titie compound is obtained, NMR (CDC1 3 ) 7.76, 6.92, 6.86, 4.15, 3.88, 3.86, 3.75 and 3.66 δ. EXAMPLE 12 Methyl 6-[(2-hydroxyedιoxy)ethoxy]indole-2-carboxylate (V) Following the general procedure of EXAMPLE 3, and making non-critical variations but substituting methyl 4-[2-(2-hydroxyethoxy)ethoxy]-2-___idocinnamate (TV, EXAMPLE 11) for methyl 4-[(2-(2-hydroxyethoxy)ethoxy)ethoxy]-Q;-azidociannamate, the titie compound is obtained, NMR (CDCI3) 7.53, 7.14, 6.83, 4.14, 3.91, 3.87 and 3.68 δ. EXAMPLE 13 6-[(2-Hydroxyedioxy)ethoxy]indole-2-carboxylic acid (VI) Following the general procedure of EXAMPLE 4, and making non-critical variations but substituting methyl 6-[(2-hydroxyethoxy)ethoxy]indole-2-carboxylate (V, EXAMPLE 12) the titie compound is obtained, NMR (d-methanol) 7.38, 6.95, 6.80, 6.63, 4.03, 3.74, 3.57, 3.51 and 3.17 δ. EXAMPLE 14 l -[6-(2-Hydroxyethoxy)ethoxyindolyl-2-carbonyl]-4-[3-(l - methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 5, and making non-critical variations but substituting 6-[(2-hydroxyedιoxy)ethoxy]indole-2-carboxylicacid (VI, EXAMPLE 13) for 6-[(2-(2- hydroxyethoxy)ethoxy)ethoxy]indole-2-carboxylicacid, die titie compound is obtained, mp 74-75°. EXAMPLE 15 l-[5-(2-(l-Piperadinyl)ethyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 6, and making non-critical variations but substituting piperidine for pyrrolidine, the titie compound is obtained, mp 150°. EXAMPLE 16 l-[5-(2-(l-Morpholinyl)ethyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 9, and making non-critical variations but substituting morpholine for pyrrolidine, die titie compound is obtained, mp 135°. EXAMPLE 17 l-[6-(2-(2-Hydroxyethoxy)ethoxy)ethoxyindolyl-2-carbonyl]-4-[N-methyl- N-(3-(l-methylethylamino)-2-pyridinyl)amiπo]piperidine (I) Following the general procedure of EXAMPLE 5, and making non-critical variations but substituting 4-(N-methyl-N-(3-(l-methylethylamino)-2-pyridinyl)amino)piperidine (PREPARAΗON 54) for 3-(l-methyledιylamino)-2-pyridinyl]piperazine, the titie compound is obtained, MS theory 540.3186, found 540.3149. EXAMPLE 18 l-[5-(3-Methylureido)-indolyl-2-carbonyl]-4-[N-methyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino]-piperidine (I) Methyl isocyanate (47 μl) is added to a solution of l-[5-aminoindolyl-2-carbonyl]-4-[N- methyl-N-(3-(l-methylethylamino)-2-pyridinyl)amino]-piperidine (VII, PREPARAΗON 56, 310 mg) in dry methylene chloride (3 ml) of at 0°. The mixture is stirred for 30 min at 0°, during which a precipitate forms, and then at 20-25° for 18 hrs. The reaction mixture is filtered and die precipitate rinsed witii cold methylene chloride to give the titie compound, NMR (methanol^ 7.60, 7.32, 7.10, 6.98, 6.69, 4.46, 3.57, 3.37, 3.08, 2.75, 2.60, 1.82, 1.59 and 1.19 δ. EXAMPLE 19 l-[5-(2-(4-Py__dyl)-edιan_sulfonamido)-indolyl-2-carbonyl]-4-[N-metiιyl-N- (3-(l-methyle_hylamino)-2-pyridinyl)amino]-piperidine (I) A mixture of 4-pyridine ethanesulfonic acid (2.32 g), phosphorus pentachloride (2.86 g) and phosphorus oxychloride (9.4 ml) is heated to 60°, stirred for 1.5 hrs, cooled to 20-25°, and diluted witii carbon tetrachloride (10 ml). The mixture is filtered and die precipitate is washed thoroughly with carbon tetrachloride, acetonitrile, and ether and dried under reduced pressure to give the sulfonyl chloride as a solid. To a solution of l-[5-aminoindolyl-2-carbonyl]-4-[N-methyl- N-(3-(l-methylethylamino)-2-pyridinyl)amino]-piperidine (VH, PREPARAΗON 56, 400 mg) in dry mediylene chloride (5 ml) under nitrogen is added this sulfonyl chloride (262 mg) and triethylamine (275 μl). The mixture is stirred at 20-25° for 24 hrs, during which an additional sulfonyl chloride (25 mg) and triediylamine (14 μl) are added, and tiien diluted widi water (3 ml). The layers are separated and die organic phase is washed wid saline (5 ml), dried over sodium sulfate, and concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 45 g), eluting widi a gradient of medianol/chloroform (2.5/97.5 - 7/93). Pooling of die appropriate fractions, having an Rf of about 0.43 by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives die titie compound, NMR (CDC1 3 ) 10.51, 8.62, 8.41, 7.71, 7.57, 7.35, 7.13, 6.98, 6.95, 6.85, 6.69, 4.62, 4.50, 3.55, 3.47, 3.40- 2.90, 2.63, 1.92, 1.63 and 1.21 δ. EXAMPLE 20 l-[5-(4-Methylpiperazin-l-ylcarbonylamino)-indolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl)]piperazine (I) Carbonyldiimidazole (0.086 g) is dissolved in dry THF (5 ml). l-[5-Aminoindolyl-2- carbonyl]-4~[3-(l-methylethylamino)-2-pyridinyl]piperazine (VH, EXAMPLE 7, 0.19 g) is dissolved in dry THF (4 ml) and added to d e carbonyldiimidazole solution over 2.4 hr. Upon die complete addition, N-methylpiperazine (55 μl) is added. The reaction mixture is allowed to stir overnight at 20-25°. The reaction is then concentrated and the concentrate is dissolved in chloroform (15 ml) and washed witii water and saline, dried over sodium sulfate, concentrated and dried under reduced pressure. The mixture is chromatographed over silica gel (20 ml) packed in chloroform eluting with 80 ml of chloroform, 100 ml each of 1%, 1.5%, 2%, 2.5%, 3%, 4%, 5%, 6%, 7%, 8% and 10% and 150 ml of 15% methanol/chloroform. Fractions having an Rf value of about 0.28 in methanol/chloroform (10/90) are collected and concentrated to give a solid. The solid is recrystallized from methanol/chloroform, adding ethyl ether after crystals start to form to give the titie compound, mp 200°. EXAMPLE 21 l-[6-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (VII) Following die general procedure of EXAMPLE 7 and making non-critical variations but starting with l-[6-nitroindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (PREPARAΗON 64, 0.32 g), the title compound is obtained, mp 158° (decomp). EXAMPLE 28 l-[5-(2-(4-pyridyl)ethanesulfonamido)indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 19, and making non-critical variations but substituting l-[5-aminoindole-2-carbonyl]-4-[3-(l-metiιylethylamino)-2- pyridinyl]piperazine (EXAMPLE 7) for l-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3- (l-methylethylamino)-2-pyridinyl)amino]piperidine, the titie compound is obtained, NMR (CDC1 3 ) 10.67, 8.72, 8.41, 7.68, 7.56, 7.36, 7.13, 6.97, 6.92, 6.84, 6.72, 4.20, 4.07, 3.55, 3.28, 3.16, 3.08 and 1.25 δ. EXAMPLE 29 l-[5-(2-Dim__hyl_minoethanesulfonamido)indole-2-carbonyl]-4-[N-metiιyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino]piperidine (I) To a solution of l-[5-aminoindole-2-carbonyl]-4-[N-m_thyl-N-(3-(l-methyle_hylamino)-2- pyridinyl)amino]piperidine (VH, PREPARAΗON 56, 400 mg) in dry methylene chloride (5 ml) under nitrogen at 0° is added triethylamine (275 μl) and 2-(dimethylamino)ethanesulfonyl chloride hydrochloride (225 mg). The mixture is stirred at 0° for 1 hr and at 20-25° for 23 hrs, during which additional sulfonyl chloride (20 mg) and trietiiylamine (14 μl) are added. The mixture is then diluted widi 4 ml of water, the layers are separated, and die organic phase is washed witii saline, dried over sodium sulfate and concentrated under reduced pressure to give a solid which is chromatographed on silica gel (70-230 mesh, 46 g), eluting with a gradient of methanol/chloroform (2.5/97.5 - 6/94). Pooling of fractions having an R f of 0.36 by TLC (methanol/chloroform, 10/90) and removal of solvent under reduced pressure gives an impure solid. Purification of this solid on two 2000 μ preparative silica gel plates, eluting with methanol/chloroform (10/90) and extracting the appropriate band, gives die title compound, NMR (CDCI3) 10.17, 7.71, 7.55, 7.35, 7.11, 6.94, 6.84, 6.69, 4.63, 4.50, 3.56, 3.45, 3.18, 3.30-3.00, 2.84, 2.63, 2.25, 1.93, 1.65 and 1.22 δ. EXAMPLE 30 l-[5-(2-Dimethylaminoethanesulfonamido)indole-2-carbonyl]-4-[3-(l- methylethylamino) -2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 29, and making non-critical variations but substituting l-[5-aminoindole-2-carbonyl]-4-[3-(l-metiιylethylamino)-2-pyridinyl]piperazine (EXAMPLE 7, 400 mg) for l-[5-aminoindole-2-carbonyl]-4-[N-metiιyl-N-(3-(l-medιylethylamino)- 2-pyridinyl)amino]piperidine, the titie compound is obtained, mp 185-188° (decomp). EXAMPLE 31 l-[5-(2-Phthalimidoedian_sulfonamido)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino]piperidine (I) To a solution of l-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(l-methyl ethylamino)-2- pyridinyl)amino]piperidine (PREPARAΗON 56, 606 mg) in dry methylene chloride (5 ml) under nitrogen is added pyridine (127 μl, 1.05 equivalents) and 2-phdιalimidoethanesulfonyl chloride (400 mg). The mixture is stirred at 20-25° for 3 days and then diluted witii methylene chloride (40 ml) and water (20 ml). The layers are separated and die organic phase is washed witii saline (15 ml), dried over sodium sulfate, and concentrated under reduced pressure to give a residue which is tiien chromatographed on silica gel (230-400 mesh, 85g, 8 psi), eluting with a gradient of methanol/chloroform (1/99-2.5/97.5). The appropriate fractions (R f = 0.33, TLC, methanol/chloroform, 5/95) are pooled and concentrated to give the titie compound, NMR (CDC1 ) 10.33, 7.80, 7.76-7.63, 7.35, 7.22, 6.95, 6.85, 6.69, 4.65, 4.51, 4.13, 3.60-3.40, 3.40-2.90, 2.64, 1.94, 1.65 and 1.22 δ. EXAMPLE 32 l-[5-(2-Aminoethanesulfonamido)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- methyledιylamino)-2-pyridinyl)amino]piperidine (I) To a solution of l-[5-(2-ph_ιalimidoedιanesulfonamido)indole-2-carbonyl]-4-[N-medιyl-N- (3-(l-methylethylamino)-2-pyridinyl)amino]piperidine (EXAMPLE 31, 675 mg) in 95% ethanol (10 ml) under nitrogen is added hydrazine monohydrate (53 μl). The mixture is stirred at 70-75° for 20 hrs during which additional hydrazine monohydrate (10 μl) is added, concentrated to remove ethanol, diluted with water (10 ml), acidified to pH 2 witii IM hydrochloric acid and stirred for 10 min. The mixture is then filtered, the filtrate is adjusted to pH 10-11, and the resulting precipitate is isolated by filtration to give die titie compound, NMR (CDC1 3 ) 9.86, 7.70, 7.56, 7.29, 7.10, 6.94, 6.84, 6.68, 4.60, 4.50, 3.56, 3.44, 3.40-2.80, 2.62, 1.93, 1.65 and 1.22 δ. The basic filtrate is extracted widi mediylene chloride (2 x 15 ml) which is then washed with saline (10 ml), dried over sodium sulfate, and concentrated under reduced pressure to give an additional amount of die title compound. EXAMPLE 33 l-[5-(2-Phthalimidoethanesulfonamido)indole-2-carbonyl]-4-[3-(l- methylediylamino)-2-pyridinyl]piperazine (_) Following the general procedure of EXAMPLE 31, and making non-critical variations but substituting l-[5-aminoindole-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 7, 553 mg) for l-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(l-methylethylamino)- 2-pyridinyl)amino]piperidine and using 2 equivalents of pyridine instead of 1.05 equivalents, the title compound is obtained, NMR (CDC1 3 ) 10.30, 7.78, 7.66, 7.36, 7.23, 6.95, 6.86, 6.73, 4.25- 4.02, 3.57, 3.44, 3.18 and 1.26 δ. EXAMPLE 34 l-[5-(2-Aminoethanesulfonamido)indole-2-carbonyl]-4-[3-(l _nethylethylamino)-2- pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 32, and making non-critical variations but substituting -[5-(2-phthalimidoethanesulfonamido)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (EXAMPLE 33, 605 mg) for l-[5-(2-(ph_ιalimidoethanesulfonamido)indole-2- carbonyl]-4-[N-methyl-N-(3-(l-methyledιylamino)-2-pyridinyl)amino]piperidine,tiιetitiecompound is obtained, NMR (CDC1 3 ) 10.62, 7.68, 7.55, 7.25, 7.07, 6.93, 6.84, 6.69, 4.20, 4.04, 3.90-3.50, 3.14 and 1.25 δ. EXAMPLE 35 l-[5-(4-Metiiyl-l-piperazinosulfonylamino)indole-2-carbonyl]-4-[N-mediyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino]piperidine (_) To a solution of 1-methylpiperazine (1.11 ml) in dry methylene chloride (20 ml) at 0° under argon is added sulfuryl chloride (1.6 ml) dropwise. The mixture is warmed to 20-25°, stirred for 1.5 hrs, and concentrated to give the crude sulfamoyl chloride intermediate. This intermediate (187 mg) is added to a solution of l-[5-aminoindole-2-carbonyl]-4-[N-metiiyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino]- piperidine (PREPARAΗON 56, 162 mg) in pyridine (1.5 ml) under nitrogen, and the resulting mixture is stirred at 20-25° for 20 hrs, diluted widi water (25 ml), and extracted witii methylene chloride (4x25 ml). The organic phase is then washed with aqueous sodium bicarbonate solution (30 ml) and saline (50 ml), dried over sodium sulfate, and concentrated under reduced pressure to give a solid which is chromatographed on four 2000 μ preparative silica gel plates, eluting with methanol/chloroform (5/95) twice. Extraction of the extract of the appropriate band gives die titie compound, NMR (CDC1 3 ) 9.94, 7.71, 7.54, 7.30, 7.13, 6.95, 6.84, 6.69, 4.64, 4.50, 3.56, 3.45, 3.25, 2.63, 2.36, 2.23, 1.95, 1.65 and 1.22 δ. EXAMPLE 36 l-[5-(Dimethylaminosulfonylamino)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino]piperidine (I) To a solution of l-[5-aminoindole-2-carbonyl]-4-[N-methyl-N-(3-(l-methyledιylamino)-2- pyridinyl)amino]piperidine (PREPARATION 56, 91 mg) in pyridine (0.5 ml) under nitrogen is added N,N-dimethylsulfamoyl chloride. The mixture is stirred at 20-25° for 16 hr and then diluted witii methylene chloride (35 ml) and IM hydrochloric acid (20 ml). The layers are separated and die organic layer is washed with IM hydrochloric acid (20 ml) and saline, dried over sodium sulfate, and concentrated to give a solid film which is tiien chromatographed on two 2000 μ preparative silica gel plates, eluting widi medianol/chloroform (5/95). The desired band is extracted and concentrated to give die titie compound, NMR (CDC1 3 ) 10.34, 7.72, 7.64, 7.56, 7.37, 7.16, 6.95, 6.84, 6.70, 4.65, 4.50, 3.56, 3.46, 3.40-3.00, 2.80, 2.63, 1.93, 1.64 and 1.22 δ. EXAMPLE 37 l-[5-(4-Methyl-l-piperazinosulfonylamino)indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperaz_ne (I) To a solution of l-methylpiperazine (1.11 ml) in dry methylene chloride (10 ml) at 0° under argon is added freshly distilled sulfuryl chloride (1.60 ml) dropwise. The mixture is warmed to 20-25° and stirred for 2.25 hrs, after which a dark brown gum is removed from die mixture. The remaining reaction mixture is concentrated under reduced pressure to give the sulfamoyl chloride intermediate (NMR (pyridine-d j ) 3.56, 2.77 and 2.40 δ). This intermediate (115 mg) is added to a solution of l-[5-aminoi_dole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (EXAMPLE 7, 200 mg) and pyridine (94 μl) in dry methylene chloride (3 ml) under nitrogen. The mixture is stirred at 20-25° for 6 days during which an additional amount of the sulfamoyl chloride (50 mg) and pyridine (40 μl) is added, concentrated under reduced pressure, and diluted with methylene chloride (30 ml) and water (10 ml). The layers are separated, die aqueous phase is extracted widi methylene chloride (2 x 25 ml), and the combined organic layers are washed witii saline (20 ml), dried over sodium sulfate, and concentrated under reduced pressure. The resulting solid is chromatographed on silica gel (230-400 mesh, 35 g, 5 psi), eluting witii a gradient of methanol/chloroform (4/96-7/93). Pooling of the appropriate fractions (Rf = 0.25, TLC, methanol/chloroform, 10/90) and concentrating gives the titie compound, NMR (CDC1 3 ) 10.45, 8.00, 7.70, 7.55, 7.29, 7.12, 6.93, 6.85, 6.72, 4.21, 4.10, 3.57, 3.23, 3.18, 2.36, 2.22 and 1.26. EXAMPLE 38 l-[5-(4-Benzyl-l-piperazinosulfonylamino)indole-2-carboπyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 37, and making non-critical variations but substituting 1-benzylpiperazine for 1-methylpiperazine, die titie compound is obtained, mp 173- 176°. EXAMPLE 39 l-[5-(l-piperazinosulfonylamino)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (I) Palladium on carbon (10%, 300 mg) is added to a solution of l-[5-(4- __;n_ylpipOT___inos fonylammo)mdole-2-carbonyl]-4-[3-(l-memyletiiylamino)-2-pyridinyl]piperazine (EXAMPLE 38, 450 mg) in methanol (50 ml). The mixture is stirred under a hydrogen atmosphere (balloon) for 4.5 hrs, under nitrogen for 17 hrs, again under hydrogen for 8 hrs and nitrogen for 17 hrs, and then under hydrogen for an additional 3 hrs. The mixture is filtered through a pad of celite and die filtrate concentrated under reduced pressure to give a solid film which is then chromatographed on silica gel (230-400 mesh, 37 g, 5-6 psi), eluting widi a gradient of methanol/chloroform (5/95-10/90). Pooling of the appropriate fractions (R f = 0.18, TLC, methanol/chloroform, 10/90) and concentrating gives the titie compound, NMR (metiιanol-d ) 7.56, 7.39, 7.18, 6.98, 6.82, 4.02, 3.63, 3.16, 3.09, 2.71 and 1.24. EXAMPLE 40 l-[5-(Morpholinosulfonylamino)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 37, and making non-critical variations but substituting morpholine (543 μl) for 1-methylpiperazine, the crude product is obtained. This residue is chromatographed on silica gel (230-400 mesh, 100 g, 6-8 psi), eluting with a gradient of ethyl acetate/hexane (35/65-100/0). Pooling of the appropriate fractions (R f = 0.16, TLC, ethyl acetate/hexane, 2 x 50/50), concentrating under reduced pressure, and triturating with methanol gives the titie compound, mp 210-211.5°. EXAMPLE 41 l-[5-Aminoindole-2-carbonyl]-4-[3-(l , l-dimethylpropylamino)-2- pyridinyl]piperazine To a solution of l-[5-nitroindole-2-carbonyl]-4-[3-(l,l-dimethylpropylamino)-2- pyridinyl]piperazine (PREPARAΗON 67, 1.00 g) in dimethylformamide/methanol (200 ml, 50/50) under nitrogen is added palladium on carbon (10 %, 250 mg). The mixture is put under hydrogen (balloon) for 4 hr and nitrogen for 17 hr, filtered through a pad of celite, and concentrated under reduced pressure to give the titie compound, NMR (CDC1 3 ) 9.25, 7.66, 7.24, 7.06, 6.88, 6.76, 6.63, 4.58, 4.05, 3.35, 3.14, 1.73, 1.35 and 0.91. EXAMPLE 42 l-[5-(4-Methylpiperazinosulfonylamino)indole-2-carbonyl]-4-[3-(l , l- dimethylpropylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 37, and making non-critical variations but substituting l-[5-aminoindole-2-carbonyl]-4-[3-(l,l-dimediylpropylamino)-2-pyridinyl]piper_-_ine (EXAMPLE 41) for l-[5-aminoindole-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyI]- piperazine, the titie compound is obtained, mp 202-205° (decomp). EXAMPLE 43 l-[5-(Methanesulfonamido)indole-2-carbonyl]-4-[3-(l,l-dimediylpropylamino)-2- pyridinyl]piperazine To a solution of l-[5-aminoindole-2-carbonyl]-4-[3-(l,l-dimethylpropylamino)-2- pyridinyljpiperazine (EXAMPLE 41, 300 mg) in dry methylene chloride (6 ml) under nitrogen is added pyridine (119 μl) and methanesulfonyl chloride (57 μl). The mixture is stirred at 20-25° for 24 hr and then diluted with methylene chloride (20 ml) and water (8 ml). The layers are separated and the organic phase is washed witii saline (8 ml), dried over sodium sulfate, and concentrated to give a solid which is tiien chromatographed on silica gel (230-400 mesh, 34 g, 5-6 psi), eluting with methanol/chloroform (2.5/97.5). Pooling of the appropriate fractions, concentration to a solid, and recrystallization from chloroform gives the title compound, mp 232-233° (decomp). EXAMPLE 44 l-[5-(4-(l , l-Dimethylpropyl)piperazino-sulfonylamino)indole-2-carbonyl]- 4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 40, and making non-critical variations but substituting l-(l,l-dimethylpropyl)piperazine (PREPARAΗON 70) for l-methylpiperazine and working up the reaction after 2 days, die titie compound is obtained, mp 158-160°. EXAMPLE 45 l-[5-Methanesulfonamidoindole-2-carbonyl]-4-[N-methyl-N-(3-(l , 1- dimethylpropylamino)-2-pyridinyl)amino]piperidine Following die general procedure of EXAMPLE 43, but substituting l-[5-aminoindole -2- carbonyl]-4-[N-methyl-N-(3-(l,l-dimethylpropylamino)-2-pyridinyl)amino]piperidine (PREPARAΗON 75) for l-[5-aminoindole-2-carbonyl]-4-[3-(l,l-dimethylpropylamino)-2- pyridinyl]piperazine and eliminating the recrystallization, the titie compound is obtained, NMR (CDCI3) 10.06, 7.70, 7.58, 7.39, 7.16, 7.08, 6.91, 6.71, 4.90, 4.63, 3.45, 3.20, 2.95, 2.64, 1.94, 1.68, 1.32 and 0.87 δ. EXAMPLE 46 l-[5-(li>iper_zinylcaι1x)nyl_mino)-indole-2-c__:bonyl]-4-[3-(l-memylethyl___ιino)-2- pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 20 and making non-critical variations but substituting piperazine for N-methylpiperazine, the titie compound is obtained, mp 209° (decomp). EXAMPLE 47 l-[5-(N-phenyl-N-methyluriedo)-indole-2-carbonyl]-4-[3-(l -methylethylamino)-2- pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 20 and making non-critical variations but substituting N-methylaniline for N-methylpiperazine, the titie compound is obtained, NMR (chloroform-d) 9.45, 7.71, 7.39, 6.95, 6.71, 6.25, 4.19, 4.05, 3.62, 3.36, 3.17, 1.26 δ. EXAMPLE 48 l-[5-(N-(2-dimethylaminoethyl)-N-methyluriedo)-indole-2-carbonyl]-4-[3-(l- methyletiιylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 20 and making non-critical variations such as the addition of N-metiιyl-2-pyrτolidinone as a cosolvent, and substituting N,N,N'- trimethylethylenediamine for N-methylpiperazine, die titie compound is obtained, NMR (chloroform-d) 10.1, 9.42, 7.68, 7.31, 7.10, 7.09, 6.95, 6.85, 6.72, 4.20, 4.07, 3.58, 3.39, 3.18, 3.0, 2.60, _.41, 1.26 δ. EXAMPLE 49 l -[5-(N-(2-dimethylaminoethyl)uriedo)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 48 and making non-critical variations but substitutingN,N-dimetiiyletiiylenediamineforN,N,N'-trimethylediylenediamine,thetitiecompound is obtained, mp 124° (decomposition). EXAMPLE 50 l-[5-(N-(2-methylaminoethyl)-N-methyluriedo)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (_) Following die general procedure of EXAMPLE 48 and making non-critical variations but substituting N,N'-dimetiιyledιylenediamine for N.N.N'-trimethylethylenediamine, the titie compound is obtained, mp 197° (decomposition). EXAMPLE 51 l-[5-(N-(3-pyridyl)uriedo)-indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 20 and making non-critical variations but substituting 3-aminopyridine for N-methylpiperazine, the titie compound is obtained, NMR (chloroform-d) 11.52, 8.79, 8.64, 8.17, 7.98, 7.58, 7.32, 7.20, 6.95, 6.81, 4.50, 3.96, 3.62, 3.03, 1.19 δ. EXAMPLE 52 l-[5-((3,5-cis-dimetiiyl-l-piperazinyl)carbonylamino)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 20 and making non-critical variations such as including N-metiιyl-2-pyrrolidinone as a cosolvent and substituting cis-2,6-dimetiιylpiperazine for N-methylpiperazine, the title compound is obtained, mp 157° (decomposition). EXAMPLE 53 l-[5-((3,5-cis-dimethyl-l-piperazinyl)_arbonylamino)-indole-2-carbonyl]-4-[3-(l,l- dimedιyletiιylamino)-2-pyridinyl]piperaz_ne (I) Following the general procedure of EXAMPLE 20 but substituting cis-3,5- dimetiiylpiperazinefor N-methylpiperazine and substituting l-[5-aminoindole-2-carbonyl]-4-[3-(l,l- dimethyledιylamino)-2-pyridinyl]piperazine(PREPARAΗON99)forl-[5-aminoindole-2-carbonyI]- 4-[3-(l-methylethylamino)-2-pyridinyl]piperazine the title compound is obtained, mp 162° (decomposition). EXAMPLE 54 l-[5-((4-methyl-l-piperazin-4-oxide)ylcarbonylamino)-indoIe-2-carbonyI]-4-[3-(l- methylethylamino)-2-pyridinyl]piper___ine (I) To a solution of l-[5-(4-methyl-l-piperazinylcarbonylamino)-indole-2-carboπyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 20, 0.1 g) in methanol (8.0 ml) is added hydrogen peroxide (3.11%, 0.22 ml). Additional hydrogen peroxide was added in portions over 3 hr (total of 1.16 ml) until total conversion of the substrate is achieved as indicated by TLC on silica gel (methanol). The mixture is concentrated, dissolved in mediylene chloride, dried over sodium sulfate and concentrated to yield die titie compound, NMR (chloroform-d) 7.60, 7.56, 7.38, 7.20, 6.98, 4.03, 3.67, 3.46, 3.20, 3.08, 1.24 δ. EXAMPLE 55 l-[5-(4-(l-methylethyl)-l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) To a solution of l-[5-(l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 46, 0.41 g) in methanol (50 ml) is added sodium cyanoborohydride (53 mg) and acetone (1 ml). Additional sodium cyanoborohydride (44.3 mg total) and excess acetone are added in portions until the reaction is complete as judged by TLC on silica gel. The mixture is acidified widi acetic acid, neutralized witii 50% aqueous sodium hydroxide and concentrated. The residue is dissolved in methylene chloride, washed with water, saturated potassium carbonate solution, and saline and dried over sodium sulfate followed by concentration. The resulting material is purified by chromatography on silica gel (100 ml) packed in medianol/chloroform (1/99) and eluted witii a methanol/chloroform gradient (1 → 5%) to give the titie compound, NMR (chloroform-d) 9.14, 7.71, 7.33, 7.17, 6.95, 6.86, 6.74, 4.06, 3.58, 3.20, 2.78, 2.60, 1.27, 1.08 δ. EXAMPLE 56 l-[5-(cis-3,4,5-trimethyl-l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 20 and making non-critical variations but substituting cis-3,4,5-trimethylpiperazine (PREPARAΗON 77) for N-methylpiperazine, the titie compound is obtained, NMR (chloroform-d) 7.91, 7.57, 7.36, 7.18, 7.01, 6.81, 4.02, 3.63, 3.10, 2.72, 2.33, 2.26, 1.25, 1.16 δ. EXAMPLE 57 l-[5-(4-methyI-l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) Carbonyldiimidazole (1.54 g) is dissolved in of dry THF (40 ml). l-[5-aminoindolyl-2- carbonyl]-4-[3-(l-metiιylethylamino)-2-pyridinylpiperazine (VH, EXAMPLE 7, 3.0 g) and N- methylpiperazine (1.3 ml) are dissolved in dry THF (75 ml) and added to the carbonyldiimidazole solution over 1.5 hr. After an additional hour the reaction is concentrated and die concentrate is dissolved in methylene chloride (125 ml) and washed with water and saline, dried over sodium sulfate, concentrated and dried under reduced pressure. The mixture is chromatographed over silica gel (450 ml) packed in 2% methanol/mediylene chloride eluting with a methanol/methylene chloride gradient (2 → 50%). Fractions with an R f value of about 0.14 in methanol/chloroform (10/90) are collected and concentrated to give a solid. The solid is dissolved in chloroform (100 ml/1 g of solid), filtered and the solution is concentrated to dryness to afford the title compound. The solid is recry stall ized from methanol/chloroform, adding ethyl ether as crystals begin to form to give the titie compound, mp 200°. EXAMPLE 58 l-[5-(4-(l,l-dime_hylpropyl)-l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3- (l-methylethylamino)-2-pyridinyl]piperazine (I) Following the general procedure for EXAMPLE 57 and making non-critical variations but substituting N-(l,l-dimethylpropyl)piperazine (PREPARAΗON 70) for N-methylpiperazine, the title compound is obtained, Mp 240-242°. EXAMPLE 59 l-[5-(4-mo holinoc__rbonylamino)-indole-2-iarbonyl]-4-[3-(l-me_hyleftyl__Ωi_ιo)-2- pyridinyl]piperazine (I) Following the general procedure for EXAMPLE 57 and making non-critical variations but substituting morpholine for N-methylpiperazine, the titie compound is obtained, mp 133-136°. EXAMPLE 60 l-[5-(4-Methyl-l-piperazinylcarbonylamino)indole-2-carbonyl]-4-[3-(l,l- dimethylpropylamino)-2-pyridinyl]piperazine (I) Following the general procedure for EXAMPLE 57 and making non-critical variations but substituting l-[5-aminoindole-2-carbonyl]-4-[3-(l,l-dimetiiylpropylamino)-2-pyridinyl]piperazine (EXAMPLE4i orl-[5-aminoindolyl-2-carbonyl]-4-[3-(l-me_ιylethylamino)-2-pyridinylpiperazine the titie compound is obtained, NMR (chloroform-d) 10.02, 7.68, 7.62, 7.21, 7.07, 6.97, 6.88, 6.61, 4.90, 4.59, 3.50, 3.38, 3.11, 2.61, 2.36, 2.23, 1.90, 1.64, 1.31, 0.86 δ. EXAMPLE 61 l-[6-[2-(2-Methoxyethoxy)ethoxyindolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridinyl]piperazine (I) 6-[2-(2-Methoxyethoxy)ethoxy]indole-2-carboxylic acid (VI, PREPARAΗON 81, 0.30 g) and 3-(l-medιyledιylamino)-2-pyridinyl]piperazine (0.26 g) is dissolved in THF (5.35 ml) and l-(ethyl-3-(dimetiιylaminopropyl)carbodiimide (EDC, 0.25 g) is added. The reaction is stirred 2.75 hr at 20-25° and poured into chloroform, washed witii saturated sodium bicarbonate and saline. The material is concentrated under reduced pressure and purified by flash column chromatography eluting with methanol/chloroform (2.5/97.5). The appropriate fractions are pooled and concentrated to provide the title compound, mp 135-136°. EXAMPLE 62 l-[6-(2-(l-Piperadinyl)ethoxy)indolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridinyl]piperazine Following the general procedure of EXAMPLE 5, and making non-critical variations but substituting 6-[(2-piperadin-l-yl)ethoxy]indole-2-carboxylic acid (PREPARAΗON 94) for 6-[(2-(2-hydroxyethoxy)ethoxy)etiioxy]indole-2-carboxylicacid, the titie compound is obtained, mp 139-141°. EXAMPLE 63 l-[5-(3-(l-Piperadinyl)propyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine (I) l-[5-(3-Chloropropyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)- 2-pyridinyl]piperazine (PREPARAΗON 86, 0.60 g), piperadine (0.115 ml) and sodium iodide (0.174 g) are placed in 5.8 ml of acetonitrile and refluxed for 28 hr. Then the reaction is diluted witii chloroform, washed with water, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with methanol/chloroform (2.5/97.5), pooling and concentrating the appropriate fractions gives the titie compound, mp 145-146°. EXAMPLE 64 l-[5-(3-(l-Piperadinyl)propyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l, 1- dimetiιyledιylamino)-2-pyridinyl]piperazine (I) Following the general procedure of EXAMPLE 5, and making non-critical variations but substituting5-[(3-(l-piperadinyl)propyl)sulfonamido]indole-2-carboxylicacid (PREPARAΗON 84) for 6-[(2-(2-hydroxyetiioxy)ethoxy)ethoxy]indole-2-carboxylic acid, he titie compound is obtained, mp 118-120°. EXAMPLE 65 l-[5-(3-(Morpholinyl-l-yl)propyl)sulfonamidoindolyl-2-carbonyl]-4-[3- (l,l-dimetiιylethylamino)-2-pyridinyl]piperazine (I) l-[5-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 7, 0.50 g) and 0.37 ml of triethylamine are dissolved in 2.6 ml of methylene chloride and cooled to 20-25°. Then 0.35 g of 3-(morpholin-l-ylpropyl)sulfonyl chloride hydrochloride (Prepared by dissolving 5.0 g of 4-morpholinepropanesulfonic acid in 10 ml of phosphorus oxychloride and adding 4.97 g of phosphorus pentachloride and stirring overnight at 20-25°. Then concentrating under reduced pressure, chasing with benzene, collecting the solids and washing with carbon tetrachloride and ether.) is added and the reaction is slowly allowed to warm to 20-25° and stirred for 4 hr. Then the reaction is diluted widi chloroform, washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with medianol/chloroform (3/97), pooling and concentrating the appropriate fractions and crystallizing from ethyl acetate gives the titie compound, mp 183-185°. EXAMPLE 66 l-[5-Methoxy-6-(2-(l-morpholinyl)ethoxy)indolyl-2-carbonyl]^-[3-(l- methyledιylamino)-2-pyridinyl]piperazine Following the general procedure of EXAMPLE 5, and making non-critical variations but substituting 5-methoxy-6-[2-(l-moφholinyl)ethoxy]indole-2-carboxylic acid (PREPARAΗON 90) for 6-[(2-(2-hydroxyetiιoxy)ethoxy)ethoxy]indole-2-carboxylic acid, die titie compound is obtained, mp 229-231°. EXAMPLE 67 l-[5-((4-Methylpiperazin-l-yl)thiocarbonylamino)indolyl-2-carbonyl]-4- [3-(l-metiiylethylamino)-2-pyridinyl]piperazine (I) l-[5-Aminoindolyl-2-carbonyI]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (PREPARAΗON 71 , 0.20 g) is dissolved in 1.4 ml of THF and is added dropwise to a 0° solution of 0.105 g of thiocarbonyldiimidazole in 1.4 ml of THF. The reaction is stirred 45 min and then methylpiperazine (0.06 ml) is added and the reaction is stirred a further 30 min at 0°. Then the reaction is diluted widi chloroform, washed widi saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with chloroform/methanol (9/1), pooling and concentrating the appropriate fractions gives the titie compound, mp 218-220°. EXAMPLE 68 l-[5-(3-(3-Morpholin-l-ylpropyl)thioureido)indolyl-2-carbonyl] -[3-(l- medιylethylamino)-2-pyridinyl]piper___ine (I) l-[5-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 7, 0.5 g) is dissolved in 2.6 ml of THF and cooled to 0°. Then 3-morpholinopropyl- isothiocyanate (0.25 ml) is added and die reaction is slowly warmed to 20-25° and stirred for 18 hr. Then the reaction is diluted widi chloroform, washed widi saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated. Crystallization from ethyl acetate/hexane provided die title compound, mp 187-189°. EXAMPLE 69 l-[5-Dimeώylaminosulfamoylaminoindolyl-2-carbonyl]-4-[3-(l-methyl- ethylamino)-2-pyridinyl]piperazine (I) l-[5-Aminoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyl]piperazine (EXAMPLE 7, 0.485 g) is dissolved in 3 ml of acetonitrile and 0.10 ml of pyridine is added. The reaction is cooled to 0° and the dimethylaminosulfamoylchloride (0.14 ml) is added in one portion. The reaction is warmed to 20-25° and stirred for 48 hr. Then it is poured into saturated aqueous sodium bicarbonate and extracted witii methylene chloride, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with a gradient of 50% ethyl acetate/hexane to 100 % ethyl acetate), pooling and concentrating the appropiate fractions gives the titie compound, mp 174-175°. EXAMPLE 70 l-[5-(Piperadin-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l-medιylethylamino)- 2-pyridinyl]piperazine l-[5-((l-Caxbobenzyloxy)piperadin-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l- methylεthylamino)-2-pyridinyl]ρiperazine (PREPARAΗON 85, 0.30 g) is dissolved in 20 ml of ethanol and 0.10 g of 10% palladium on carbon is added. The reaction is placed on a Parr hydrogenator under 40 psi of hydrogen for 4 hr. The reaction is filtered dirough celite, concentrated under reduced pressure and crystallized from ethyl acetate/hexane/metiianol to provide die titie compound, mp(dec) 172-178°. EXAMPLE 71 l-[5-((l-(l-MethylethyIpiperadin-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l- methyl_dιyl_m_no)-2-pyridinyl]piperazine l-[5-(Piperadin-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridinyI]- piperazine (EXAMPLE 70, 0.40 g) and acetone (0.066 ml) are dissolved in 1.6 ml of methanol and sodium cyanoborohydride (0.054 g) is added. After 1 hr of stirring at 20-25°, 10-15 mg of sodium cyanoborohydride and 10-15 ml of acetone are added every hour for 7 hr. Then the reaction is stirred overnight at 20-25°. It is diluted with chloroform, washed widi saturated sodium bicarbonate, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Crystallization from ethyl acetate afforded die titie compound, mp 217-219°. EXAMPLE 72 l-[5-TrifluoroacetamidoindolyI-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridyl] piperazine (I) l-[5-Ami_κ)indolyl-2-ca__x)nyl]-4-[3-(l-medιyledιylamino)-2^yridyl]piper_zine (EXAMPLE 7, 0.30 g, 0.79 mmol) is dissolved in 1.6 ml of methylene chloride and pyridine (0.064 ml, 0.79 mmol) is added. The reaction was cooled to 0° and trifluoroacetic anhydride (0.11 ml, 0.79 mmol) is added dropwise. The reaction is stirred for 2 hr at 0° and tiien an additional 0.2 equivalents of trifluoroacetic anhydride is added and die reaction was stored at 0° for 18 hr. The mixture is diluted with chloroform, washed witii water, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography, eluting with methanol/chloroform (2/98), pooling and concentration of the appropriate fractions gives the titie compound, mp 215-218°; NMR(300 MHz, CD 3 OD) 7.88, 7.81, 7.47, 7.36, 7.30, 6.90, 6.78, 3.95, 3.54, 3.01, 1.16 δ. EXAMPLE 73 l-[5-Methoxy_arbamoylindolyl-2-carbonyl]-4-[3-(l-mediylethylamino)-2-pyridyl] piperazine l-[5-Amir_oindolyl-2-carbonyl]-4-[3-(l-m__hyle_hyl_mino)-2^yridyl]piper_zine (EXAMPLE 7, 0.30 g, 0.79 mmol) is dissolved in 1.6 ml of methylene chloride and pyridine (0.064 ml, 0.79 mmol) is added. The reaction is cooled to 0° and methyl chloroformate (0.06 ml, 0.79 mmol) is added dropwise. The reaction is stirred for 2 hr at 0° and die reaction was stored at 0° for 18 hr. Then it was diluted with chloroform, washed with water, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by recrystallization from methanol/hexane gives the title compound, mp 230-231°. EXAMPLE 74 l-[5-(r,l'-dioxo-2'-isothiazolidinyI)indolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridyl]piperazine l-[5-(3-CUoropropylsulfonamidoindolyl-2-carbonyl]-4-[3-(l-methyle_hylamino)-2-pyridyl]- piperazine (PREPARAΗON 86, 0.60 g, 1.16 mmol) is dissolved in 5.8 mL of acetonitrile and 0.115 ml of piperidine (3.48 mmol) and 0.174 g of sodium iodide (1.16 mmol) is added and the reaction was refluxed for 28 hr. Then the reaction is diluted with chloroform, washed with saturated sodium bicarbonate, water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with methanol/chloroform (2.5/97.5), pooling and concentration of die appropriate fractions gives the title compound, mp 215-217°. EXAMPLE 75 l-[5-(4-Methylpiperazin-l-ylcarbonylamino)indolyl-2-carbonyl]-4-[3-(l,l- dimetiιyledιylamino)-2-pyridyl]piperazine (I) Following the general procedure of EXAMPLE 6, and making non-critical variations but substituting l-[3-(l,l-dimethylethylamino)-2-pyridyl]piperazine (PREPARAΗON 97) for l-[3-(l-methylethylamino)-2-pyridinyl]piperazine and 5-(4-methylpiperazin-l- ylcarbonylamino)indole-2-carboxylicacid (Preparation 101) for 5-nitroindole-2-carboxylic acid, the titie compound is obtained, mp 183-185°. EXAMPLE 76 l-[5-(rrifluoromedιanesulfonamido)indolyl-2-carbonyl]-4-[3-(l-meuiyletiιylamino)- 2-pyridyl]piperazine l-[5-aminoindolyl-2-carbonyl]-4-[3-(l-methylediylamino)-2-pyridyl]piperazin EXAMPLE 7, 1.0 g) is dissolved in 18 ml of dichloromethane and cooled to -78°. Then triethylamine (0.37 ml) is added followed by die dropwise addition of triflic anhydride (0.45 mL) and the reaction is stirred for 1 hr. Then it is diluted witii chloroform, extracted with saturated aqueous sodium bicarbonate, dried and concentrated. Purification by flash column chromatography eluting with ethyl acetate/hexane (60/40) and recrystallization from ethyl acetate/hexane gives the titie compound, mp 282-283°. CHART A CO-O-X-j (V) CHART A - Continued hydrolysis 10 (IV) Coupling CHART B d)

Claims: CLAIMS 1. A substituted indole of formula (I) where R j is -CH 2 - or -CO-; where Z j is N N \_C'c__ 2 )_ 2 (z-o where n^ is 1 or 2 and n 2 is 1 or 2, N CH ^ \-(CH 2 )ιι 2 (Z-II) where Z2 is -N(Z 2 . 1 )- where Z 2 _! is C j ^ alkyl and where n j and n 2 are as defined above; where X j and X 2 are -H, -O-C r C 3 alkyl, -O-(CH 2 CH 2 -O-) n3 -X 1 _ 1 where n 3 is 1 thru 4, where X is -H or C r C 4 alkyl, -O-SO 2 -(CH 2 ) n 4-N(X 1 . 2 )(X 1 .3) where n is 1 thru 3, where X 2 and X^ are the same or different and are -H, C j -C 6 alkyl, -φ, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl and where X j . 2 and Xι, 3 can be taken togedier widi the attached nitrogen atom, and odier heteroatom if necessary, to form a ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1- piperazinyl, 1-morpholinyl and 1-piperazinyl optionally substituted in the 4-position with C1-C5 alkyl, in the 3- and/or 5- position with C j -C 3 alkyl, and N-oxides thereof -O-SO 2 -(CH 2 )-4-X 1 _8 whe- _ X g is 2-pyridinyl, 3-pyridinyl and 4-pyridinyl and where n 4 is as defined above, -O-CO-(CH 2 n 4-NX 1 _2Xι_3 where n , X\. and γ_ 3 are as defined above, -NH-CO-(CH2) n 4-NX 1 _ 2 X 1 _3 where n , X j _ 2 and X^ are as defined above, -N(X 1 _ 4 )-SO 2 -X 1 _5 where X l is C1-C3 alkyl, where X 5 is C r C 4 alkyl and where X 1- and X^ 5 are taken together to form a heterocyclic ring of 5 or 6 atoms, -N X^-CO-NtX^MCH^-N X^) CX1-3) where the X 1 7 s are the same or different and are -H or C1-C3 alkyl, and where n 4 , X j _ 2 and X j _ 3 are as defined above, -N(Xi_7)-SO2-(CH2 n 4-Xi_8 where n 4 , X^ and X j _ 8 are as defined above, -N X^-CO-N^^MCH^-X^g where n 5 is 0 thru 3 and where X j . 7 and X j . 8 are as defined above, -NX^-SO^CH^-Np .^P-^) where n 4 , X l . 2 , X χ . 3 and X^ are as defined above, -NX( 1 . 7 )-CO-O-X 1 ^ where X w is C r C 4 alkyl or -(CH 2 ) a4 -N(X l , 2 )(X l . 3 ) where n , Xι_ , X1.3 and X j _ 7 are as defined above, where X j _ 2 , Xχ_3 and Xγ_η are as defined above, -NH-CO-CF3, -O-SO 2 -CF 3 , -NH-SO2-CF 3 , -N(X 1 . 7 )-SO 2 -N(X 1 _ 2 )(X 1 _3) where X j . 2 , X^ and X .η are as defined above, -NH-CO-[4-(l-X 1 . 2 )piperidinyl], widi the proviso that one, but only one, of Xγ or X 2 must be -H or -0-CyC alkyl, is -N=, -CH=, -N(O)=, R 7 is -C O-R 7 . n where R 7 . π is C r C 6 alkyl, -CO-N(R 7 .3)(R 7 ^) where R7.3 and R 7 _ are the same or different and are -H or -C 6 alkyl, -N(R 7 . 5 )(R 7 ^) where R 7 . 5 is -Cg alkyl, -C(R 7 _ 15 )^l7_ 16 )-(R _ 1 7) where R7.15 and R7.16 are the same or different and are -H or C -C 3 alkyl and where R7.17 is C 2 -C 5 alkenyl containing 1 or 2 double bonds or C 2 -C 5 alkynyl containing 1 triple bond, -CH 2 -CH 2 -OH, -CH 2 -CH 2 -CH 2 -OH, -CH(CH 3 )CH 2 -O-CH 3 , -CH(CH 3 )CH 2 -OH, -CH 2 -CF 3 , -CH 2 -cyclopropyl, -CH 2 -CH F, -CH 2 -CH 2 -C»N, -C*R 7 _ 18 -(CH 2 ) nl 4-C*H 2 where R 7 . lg is -H or -CH 3 , n 14 is 1 thru 5 and die carbon atoms marked with an asterisk Q are bonded to each other to resulting in the formation of a ring, -(CH 2 )n 1 -N(R 7 _7)(R7_ g ) where n j is as defined above and where R 7 . 7 and R 7 _ g are the same or different and are -H or alkyl, and where R7.7 and R 7 _ 8 are taken togedier with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, 1-aziridinyl, and where R 7 ^ is -H, C r C 6 alkyl, -C(R7_ 1 5)(R 7 _ 1 6)- (R7.17) where 7.15, - .i β and R 7 . 17 are as defined above, -CH 2 -CH 2 -OH, -CH 2 -CH 2 -CH 2 -OH, -CH 2 CF 3 , -CH 2 -CH 2 F , -CH 2 -CH 2 -C»N, or where R 7 . 5 and R 7 _g are taken togedier with the attached nitrogen atom to form a heterocyclic ring selected from die group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl, N-morpho¬ linyl or 1-aziridinyl, -(CH2) n 4-N(R 7 _ )(R7_ 10 ) where n 4 is as defined above and where R 7 . 9 and R 7 . 10 are die same or different and are -H or Cj-C4 alkyl, and where R 7 . 9 and 7.10 are ^e" togedier with the attached nitrogen atom to f m a heterocyclic ring selected from die group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl or N-morpholinyl, R 8 is -N=, -CR 8 1 = where R SΛ is -H, -F, -Cl, -Br, -CF 3 , -NO 2 , -COCF3, C j -C 6 alkyl, CγC 3 alkylthio, -OH, -O-Rg_ 2 where R 8 . 2 is C j -Cg alkyl, -φ, -CO-R 8 . 3 where R 8 . 3 is C j -C 6 alkyl or -φ, -NH(Rg_4) where 8 _4 is C r C 6 alkyl, -C(R 8 _7)(Rg_g)-(Rg_9) where R 8 . 7 and R 8 . 8 are the same or different and are -H or C j ^ alkyl and where R 8 . 9 is C 2 -C 5 alkenyl containing 1 or 2 double bonds or C 2 -C5 alkynyl containing 1 triple bond, -NR 8 . 5 -CO-R 8 ^ where R 8 . 5 is -H or C r C 6 alkyl and R 8 5 is -H, C r C 6 alkyl or C C 3 alkoxy; is -N=, - Rg.^ where R^ is -H, -F, -Cl, -Br, -NO 2 , -COCF 3 , C r C 6 alkyl, C r C 3 alkylthio, -OH, -O-R9_ 2 where R 9 . 2 is C r C 6 alkyl, -φ, -CO-R^ where R 9 . 3 is C r C 6 alkyl or -φ, -^(R ^)(Rg-s) where R9.4 and R^ are the same or different and are -H, C r C 6 alkyl, -C(R 9 _ )(R 9 _ 9 )-(R 9 _ 10 ) where R 9 . 8 and R < )_ 9 are the same or different and are -H or CγC 3 alkyl and where R 9 .JO is C 2 -C5 alkenyl containing 1 or 2 double bonds or C2-C5 alkynyl containing 1 triple bond, R9_ 4 and Rg_5 are taken together with the attached nitrogen atom to form a heterocyclic ring selected from the group consisting of 1-pyrrolidinyl, 1-piperidinyl, 1- piperazinyl or N-morpholinyl, -NR^-CO -R^ where R^ is -H or C r C 6 alkyl and g j is -H, C r C 6 alkyl or CyC 3 alkoxy; R 10 is -N=, •CR 10-1 = here R 10-l is "H > - F ' - CI ' "Br > "CF 3> -N0 2 , -COCF3, -Cg alkyl, C r C 3 alkylthio, -OH, -O-R 10 . 2 where R 10 . 2 is C C 6 alkyl, -φ, -CO-R 10 . 3 where R 10 . 3 is C^Cg alkyl or -φ, -N(R 10 ^)(Rιo-5) where RJO_4 and R 10 _5 are the same or different and are -H, C r C 6 alkyl, -C(Rj 0 . )(Rιo-9)-(Rιo-ιo) where RJO-S and RJO-9 ∞ me same or different and are -H or ^^ alkyl and where io-io i C 2 -C5 alkenyl containing 1 or 2 double bonds or C 2 -C 5 alkynyl containing 1 triple bond, -NR 10 ^-CO-R 10 _7 where R 10 ^ is -H or C j -C 6 alkyl and RJO-7 is -H, C j -Cg alkyl or C -C 3 alkoxy; widi die proviso that not more than two of R , R 8 , R 9 and R 10 are -N = ; enantiomers, pharmaceutically acceptable salts, hydrates and solvates tiiereof. 2. A substituted indole (I) according to claim 1 where Zγ is (Z-0 where and n 2 are 1. 3. A substituted indole (I) according to claim 1 where Z j is (Z-π) where \\γ and n 2 are 1. 4. A substituted indole (0 according to claim 3 where Z^ is C j alkyl. 5. A substituted indole (I) according to claim 1 where Rγ is -CO-. 6. A substituted indole (I) according to claim 1 where Rg is -N= . 7. A substituted indole (0 according to claim 1 where R 8 is -CR 8 _ι= where R _! is -H, where -CR 9 _ 1 = where R^ j is -H and where -CRι 0 _ι= where \ Q .\ is -H. 8. A substituted indole (0 according to claim 1 where R 7 is -N(R 7 . 5 )(R 7 _^) where R 7 . 5 is C 2 -C 4 alkyl and where R 7 ^ is -H. 9. A substituted indole (I) according to claim 8 where R 7 _ 5 is i-propyl. 10. A substituted indole (I) according to claim 1 where one of X j or X 2 is selected from the group consisting of -Np_ 1 . 7 )-CO-N(X 1 . 2 )P_ 1 . 3 ) and -N(X 1 . 7 SO 2 -N(X 1 . 2 )(X 1 .3). 11. A substituted indole (0 according to claim 1 where one of Xγ or X 2 is -H. 12. A substituted indole (0 according to claim 1 which is selected from die group consisting l-[6-(2-(2 -ιydroxye_ιoxy)ethoxy)etiιoxyindolyl-2-carbonyl]-4-[3-(l-metiιylethylamino)-2- pyridinyl]piρeraziπe, l-[5-(2-(li)yrrolidino)ethyl)sulfonamideindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[6-(2-hydroxyethoxy)ethoxyindolyl-2-carbonyl]-4-[3-(l-methylethylarnino)-2- pyridinyl]piperazine, l-[5-(2-(l-piperadinyl)ethyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(2-(l-morpholinyl)ethyl)sulfonamidoindolyl-2-carbonyl]^-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[6-(2-(2-hydroxyethoxy)ethoxy)ethoxyindolyl-2-carbonyl]-4-[N-methyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino]piperidine, l-[5-(3-methylureido)-indolyl-2-carbonyl]-4-[N-methyl-N-(3-(l -methyl ethyl am ino)-2- pyridinyl)amino]piperidine, l-[5-(2-(4-pyridyl)-ethanesulfonamido)-indolyl-2-carbonyl]-4-[N-methyl-N-(3-(l- me_hyle_hylamino)-2-pyridinyl)amino]piperidine, l-[5-(4-methylpip_r_2in-l-ylcarbonylamino)-indolyl-2-carbonyl]-4-[3-(l-medιyle_ιylamino)- 2-pyridinyl)amino]piperazine, l-[5-(2-(4-pyridyl)ethanesulfonamido)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(2-dimethylaminoethanesulfonamido)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- metiiylethylamino)-2-pyridinyl)amino]piperidine, l-[5-(2-dimethylaminoethan_sulfonamido)indoIe-2-carbonyl]-4-[3-(l-methyletiιylamino)-2- pyridinyl]piperazine, l-[5-(2-phthalimidoethanesulfonamido)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- methyledιylamino)-2-pyridinyl)amino]piperidine, l-[5-(2-aminoeώ__ esulfon_mido) dole-2-c_xbonyl]-4-[N-medιyl-N-(3-(l-me_ιyle_ιylamino)- 2-pyridinyl)amino]piperidine, l-[5-(2-phthalimidoethanesulfonamido)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(2-aminoethanesulfonamido)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(4-methyl-l-pipera__inosulfonylamino)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- methyle__.ylamino)-2-pyridinyl)amino]piperidine, l-[5-(dimethylaminosulfonylamino)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- metiιyIethylamino)-2-pyridinyl)amino]piperidine, l-[5-(4-methyl-li ) iper___mosulfonylamino)indole-2-carbonyl]-4-[3-(l-me_hyle_hylamino)-2- pyridinyl]piperazine, l-[5-(4-benzyl-l^ ) iperazinosulfonylamino)indole-2-carbonyl]-4-[3-(l-methyled ylamino)-2- pyridinyl]piperazine, l-[5-(l-piperazinosulfonylamino)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(morpholinosulfonylamino)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(4-methylpiperazinosulfonylamino)indole-2-carbonyl]-4-[3-(l,l-dimetiiylpropylamino)- 2-pyridinyl]piper___ine, l-[5-(methanesulfonamido)indole-2-carbonyl]-4-[3-(l, l-dimethylpropylamino)-2- pyridinyljpiperazine, l-[5-(4-(l , l-dimethylpropyl)piperazino-sulfonylamino)indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine, l-[5-metiιanesulfonamidoindole-2-c_xbonyl]-4-[N-methyl-N-(3-(l,l-dimethylpropylamino 2- pyridinyl)amino]piperidine, l-[5-(l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(N-phenyl-N-methyluriedo)-indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(N-(2-dimethylaminoethyl)-N-methyluriedo)-indole-2-carbonyl]-4-[3-(l- methylediylamino)-2-pyridinyl]piperazine, l-[5-(N-(2-dimethylaminoethyl)uriedo)-indole-2-carbonyl]-4-[3-(l-metiiylethylamino)-2- pyridinyl]piperazine, l-[5-(N-(2-methylaminoethyl)-N-methyluriedo)-indole-2-carbonyl]-4-[3-(l- methyledιylamino)-2-pyridinyl]piperazine, l-[5-(N-(3-pyridyl)uriedo)-indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyljpiperazine, l-[5-((3,5-cis-dimethyl-l-piperazinyl)carbonylamino)-indole-2-carbonyl]-4-[3-(l- me_iylethylamino)-2-pyridinyl]piperazine, l-[5-((3,5-cis-dimethyl-l-piperazinyl)carbonylamino)-indole-2-carbonyl]-4-[3-(l,l- dimethyletiιylamino)-2-pyridinyl]piperazine, l-[5-((4-methyl-l-piperazin-4-oxide)ylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine, l-[5-(4-(l-methylethyl)-l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- metiιylethylamino)-2-pyridinyl]piperazine, l-[5-(cis-3,4,5-trimethyl-l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine, l-[5-(4-(l,l-dimethylpropyl)-l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- methylethylamino)-2-pyridinyl]piperazine, l-[5-(4-morpholinocarbonylamino)-indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(4-methyl-l-piperazinylcarbonylamino)indole-2-carbonyl]-4-[3-(l , l - dimedιylpropylamino)-2-pyridinyl]piperazine, l-[6-[2-(2-methoxyethoxy)ethoxyindolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridinyl]piperazine, l-[6-(2-(l -pip eradinyl)ethoxy)indolyl-2-carbonyl]-4-[3-(l -methy lethyl- amino)-2-pyridinyl]piperazine, l-[5-(3-(l-piperadinyl)propyl)sulfonamidoindolyl-2-carbonyl]-4-[3-(l - me_hylethylamino)-2-pyridinyl]piperazine, l-[5-(3-(l-piperadinyl)propyl)sulfonamidoindoIyl-2-carbonyl]-4-[3-(l , l- dimethylethylamino)-2-pyridinyl]piperaz_ιe, l-[5-(3-(morpholinyl-l-yl)propyl)sulfonamidoindolyl-2-carbonyl]-4-[3- (1,1 -dimethylethylamino)-2-pyridinyl]piper azine, l-[5-Medιoxy-6-(2-(l-moφholinyl)e_ιoxy)indolyl-2-carbonyl]-4-[3-(l-metiιylethylamino)-2- pyridinyl]piperazine, 1 -[5-((4-methylpiper azin- 1 -yl)thiocarbonylamino)indolyl-2-carbonyl]-4-[3-(l - methylethylamino)-2-pyridinyl]piperazine, l-[5-(3-(3-moφholin-l-ylpropyl)thioureido)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)- 2-pyridinyl]piperazine, 1 -[5 -dim ethyl amino sulf amoylaminoindolyl-2-carbonyI]-4-[3-(l-methyl- ethyl_mino)-2-pyridinyl]piperazine. 13. A substituted indole (0 according to claim 12 which is selected from the group consisting l-[5-(4-methyl-l-piperazinosulfonylamino)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- methylethylamino)-2-pyridinyl)amino]piperidine, l-[5-(4-methyl-l-piper___inosulfonyl____ino)indole-2-carbonyl]-4-[3-(l-metiιyledιylamino)-2- pyridinyl]piperazine, l-[5-(4-methylpiperaz_nosulfonylamino)indole-2-carbonyl]-4-[3-(l,l-dimedιylpropylamino)- 2-pyridinyl]piperazine, l-[5-(4-(l-methylethyl)-l-piperazinylcarbonylamino)-indole-2-carbonyl]-4-[3-(l- methylediylamino)-2-pyridinyl]piperazine, l-[5-(4-memyl-l-piperazinylca__<)nyl__--_r_o indole-2-c_rbonyl]-4-[3-(l-meώ pyridinyl]piperazine. 14. A substituted indole (I) according to claim 13 which is selected from the group consisting l-[5-(4-methyl-l-piperazinosulfonylamino)indole-2-carbonyl]-4-[N-methyl-N-(3-(l- methyletiιylamino)-2-pyridinyl)amino]piperidine, l-[5-(4-methyl-li)iperazinosulfonylamino)indole-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-(4-memyl-l-piperazinylcarbonyl_mino)-indole-2-c_jbonyl]^[3-(l-methyl__hyl___ι_no)-2- pyridinyl]piperazine. 15. A compound selected from the group consisting of l-[5-(piperadin-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridinyl]piperazine, l-[5-((l-(l-medιyle_hylpiperadin-4-yl)amido)indolyl-2-carbonyl]-4-[3-(l-metiιylethylamino)- 2-pyridinyl]piperazine, l-[5-methoxyc_rbamoylindolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2-pyridyl]piperazine, l-[5-( , -dioxo-2 , -isothiazolidinyl)indolyl-2-carbonyl]-4-[3-(l-methylethyl- amino)-2-pyridyl]piperazine, l-[5-(trifluoromethanesulfonamido)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)-2- pyridyl]piperazine. 16. A compound according to claim 15 which is l-[5-(trifluoromethanesulfonamido)indolyl-2-carbonyl]-4-[3-(l-methylethylamino)- 2- pyridyl]piperazine. 17. A compound selected from the group consisting of l-[5-Aminoindole-2-carbonyl]-4-[3-(l,l-dimethylpropylamino)-2-pyridinyl]piperazine, l-[5-(methanesulfonamido)indole-2-carbonyl]-4-[3-(l,l-dimethylpropylamino)-2- pyridinyl]piperazine, l-[5-mema_ esulfon_midoindole-2-c_xbonyl]-4-[N-methyl-N-(3-(l,l-dimediylpropylamino)-2- pyridinyl)amino]piperidine, l-[6-(2-(l-piperadinyl)ethoxy)indolyl-2-carbonyl]-4-[3-(l-methylethyl-amino)-2- pyridinyl]piperazine, l-[5-medιoxy-_ 2-(l-morpholinyl)etiιoxy)indolyl-2-carbonyl]-4-[3-(l-metiιyletiιylamino)-2- pyridinyl]piperazine.

Inventors: ROMERO DONNA LEE, THOMAS RICHARD CHARLES, ROMERO, DONNA, LEE, THOMAS, RICHARD, CHARLES
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1992
Main classification: C07D417
IPC codes: A61K31, A61P31, A61P37, C07D213, C07D401, C07D403, C07D417