Abstract:
The present invention provides a novel series of indeno[1,2-c]quinolin-11-one derivatives and further provides their preparation methods as well as applications. Said applications includes utilizing such derivatives as pharmaceutical compositions for treating cancers; moreover, said applications includes the capability possessed by such derivatives to effectively inhibit cancer cell growth as well as the activity of Type I topoisomerases and can be further applied for cancer treatment.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    This invention relates to the development of anticancer drugs, in particular, featuring a series of novel indeno[1,2-c]quinolin-11-one derivatives, preparation methods and applications as well as the evaluation of the anticancer activity of the inventive drugs. 
         [0003]    2. Description of the Prior Art 
         [0004]    Cancers arise from the abnormal proliferation of DNA. Therefore, selectively destroying the DNA of cancer cells without damaging the DNA of normal cells is highly desired. However, it is difficult to differentiate the DNAs between normal cells and cancer cells. Consequently, specific ‘targeted therapy’ was developed following the identification of the differences between normal cells and cancer cells, and when combined with other chemotherapies or radiation therapies, targeted therapy can significantly reduce the side effects and provide better treatment outcomes. Thus, targeted therapy currently is a popular field in studying cancer treatments. Because topoisomerases have been found to play an indispensible role in DNA replication, they have become the object of targeted therapy for anticancer treatments. The anticancer drug camptothecin discovered by M. E. Wall and M. C. Wani in 1966 through systematic screening of natural substances is an inhibitor for type I topoisomerases. 
         [0005]    Unfortunately, camptothecin has numerous disadvantages and thus cannot be used for clinical treatment. For example, the lactone ring can be easily hydrolyzed to hydroxycarboxylate in vivo at the normal pH and then binds to serum albumin and lose its effect of inhibiting the function of type I topoisomerases. In addition, the structure of the tricomplex of camptothecin-Top I-DNA is not stable because the complex is not maintained by covalent bonds and water solubility of camptothecin is poor which causes lower bioavailability. The p-glycoprotein (MDR1, ABCB1) efflux transporter proteins in the cell membrane transport the drugs out of the cells and more important is that some tumor cells have slowly developed resistance and adverse drug side effects against camptothecin. As a result, a number of water-soluble semi-synthetic drugs were developed even after commercialization of camptothecin such as Topotecan (HYCAMTIN®) which is used for treating ovarian cancer and Irinotecan (CAMPTO®) which is used for treating colon cancer and both have issues when used for clinical treatment. 
         [0006]    Hence, based on the importance of topoisomerase inhibitors in development of anticancer drugs, the inventor of this application developed a series of novel indeno[1,2-c]quinolin-11-one derivatives and disclosed the preparation methods as well as relevant applications herein after a number of innovative improvements. 
       SUMMARY OF THE INVENTION 
       [0007]    In one aspect, present invention provides a formula I compound: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0000]    wherein the R group is selected from the groups consisting of: i) haloformyl, amino, hydroxy and thiol groups, ii) linear alkyl chains of N(CH 2 ) n H, alkyl groups with substituted side chains and alkyl side chains with a substituted amino group, NH(CH 2 ) n N(CH 2 ) n , O(CH 2 ) n  and S(CH 2 ) n OH, wherein 1≦n≦10, iii) nitrogen-containing cycloalkyl groups and heterocyclic compounds of C 3-12  which contain 1 to 3 heteroatoms selected from O, S and N, wherein the ortho-, para- and meta-position can be further selected independently from one of the following functional groups comprising (CH 2 ) n  alkyl groups, (CH 2 ) n C 3-12  cycloalkyl groups, (CH 2 ) n C 3-12  nitrogen-containing cycloalkyl groups, (CH 2 ) n  benzene rings and (CH 2 ) n COC 3-12  nitrogen-containing cycloalkyl groups, wherein 0≦n≦10, wherein the nitrogen-containing cycloalkyl groups or the benzene rings can be further substituted by one or more substitution groups selected from the following groups comprising alkyl groups containing C 1-12 , amino groups, nitro groups, hydroxyl groups, cyano groups, halogen groups, un-substituted or halogen group substituted C 1-5  alkyl groups, un-substituted or halogen group substituted alkoxy groups, and their pharmaceutically acceptable salts, stereoisomers and enantimoers. 
         [0008]    According to the invention, the functional groups of ii) for substitution are selected from the groups consisting of methylamino group, dimethylamino group, 2-(diethylamino)ethyl-amine and 2-hydroxyethyl ethyl sulfide. 
         [0009]    According to the invention, the functional groups of iii) is selected from the groups consisting of pyrrolidin-1-yl, piperidin-1-yl, 4-methyl-piperazin-1-yl, azepan-1-yl, morpholino, thiomorpholino, piperazin-1-, 2-methyl-piperazin-1-yl, 4-methyl-piperazin-1-yl, 4-ethyl-piperazin-1-yl, 4-cyclopentyl-piperazin-1-yl, 4-(piperidin-1-yl) piperidin-1-yl, 4-phenyl-piperazin-1-yl, 4-benzyl-piperazin-1-yl, 4-(2-fluorophenyl)piperazine-1-yl, 4-(2-methoxyphenyl)piperazin-1-yl, 4-(3-methoxyphenyl)piperazin-1-yl, 4-(1-methyl-piperidin-4-yl)piperazin-1-yl, 4-(1,4-dioxo-8-aza-spiro[4,5]dec-8-yl, 4-((piperazin-1-yl) (piperidin-1-yl) methanone), 4-(3-(piperidin-4-yl) propyl) piperidin-1-yl, hydroxy, and methoxy. 
         [0010]    According to the invention, the compound is selected from the groups consisting of
   9-Chloro-6-(methylamino)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(dimethylamino)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(pyrrolidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-methyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   6-(azepan-1-yl)-9-chloro-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-morpholino-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-thiomorpholino-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(2-methyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-methyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-ethyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-cyclopentyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(piperidin-1-yl) piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-phenyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   6-(4-benzyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(2-fluorophenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(2-methoxyphenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(3-methoxyphenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(1-methyl-piperidin-4-yl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(1,4-dioxo-8-aza-spiro[4,5]dec-8-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-((piperazin-1-yl) (piperidin-1-yl)methanone))-11H-indeno[1,2-c]quinolin-11-one, and   9-chloro-6-(4-(3-(piperidin-4-yl) propyl) piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   6-(2-Hydroxyethylthio)-9-chloro-11H-indeno[1,2-c]quinolin-11-one,   6-hydroxy-9-chloro-11H-indeno[1,2-c]quinolin-11-one,   6-methoxy-9-chloro-11H-indeno[1,2-c]quinolin-11-one, and their salts.   
 
         [0037]    In another aspect, the invention provides a pharmaceutical composition comprising of the effective dose of the abovementioned compound and at least one of the pharmaceutically acceptable vehicles, diluents or excipients. 
         [0038]    In the other aspect, present invention provides an application of the abovementioned compound which can be used to produce pharmaceutical products capable of inhibiting the activity of type I topoisomerases. 
         [0039]    In still another aspect, the invention provides an application of the abovementioned compound which can be used to produce pharmaceutical products for cancer treatment. 
         [0040]    In one aspect, the invention provides a method for inhibiting type I topoisomerase activity including administration of an effective dose of the abovementioned compound. 
         [0041]    According to the invention, the cancers are selected from the following list: leukemia, non-small cell lung cancer, colorectal cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer. In another aspect, present invention provides a method used for producing the compound disclosed in claim  1 , and the method comprising (1) Mix isatin, 2-(4-chlorophenyl) acetic acid and sodium acetate at 200° C. for 3 hours, allow cooling before adding acetic acid and collect the precipitate following extraction and filtration. Wash the precipitate with acetic acid, water and n-hexane to give an intermediate product and add the intermediate product to phosphoryl trichloride and reflux at 150° C. for 48 hours. Upon completion, allow cooling to room temperature followed by addition of 0° C. ice water. Collect the resulting precipitate after extraction and filtration and place in 10% aqueous sodium bicarbonate solution for 1 hour with vigorous stirring. The crude product was recrystallized from dichloromethane after washing with water to give 6,9-dichloro-11H-indeno[1,2-c]quinoline-11-one (TC-XCl-1), (2) Dissolve 6,9-dichloro-11H-indeno[1,2-c]quinoline-11-one obtained from step 1 in N,N-dimethylformamide and add methylamine or N1,N1-diethylethane-1,2-diamine followed by addition of N,N-diisopropylethylamine to catalyze the reaction at 150° C. for 4 hours. The resulting mixture was poured into ice water and incubated for 10 to 20 minutes to give the precipitate which was then recrystallized by ethanol to produce the compounds 9-chloro-6-(dimethylamino)-11H-indeno[1,2-c]quinolin-11-one (SJ-1) and 6-(2-(diethylamino)ethylamine yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-3), (3) Dissolve the 6,9-dichloro-11H-indeno[1,2-c]quinoline-11-one obtained from step (1) in dimethyl formamide, add secondary amines followed by addition of pyridine to catalyze the reaction at 150° C. for 4 hours. The mixture resulted at the end of reaction was poured into ice water and incubated for 10 to 20 minutes to give the precipitate which was then recrystallized by ethanol to produce the compounds which are selected from the following groups consisting of 9-chloro-6-(dimethylamino)-11H-indeno[1,2-c]quinolin-11-one,
   9-chloro-6-(pyrrolidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-methyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   6-(azepan-1-yl)-9-chloro-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-morpholino-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-thiomorpholino-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(2-methyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-methyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-ethyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-cyclopentyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(piperidin-1-yl) piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-phenyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   6-(4-benzyl-piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(2-fluorophenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(2-methoxyphenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(3-methoxyphenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(1-methyl-piperidin-4-yl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-(1,4-dioxo-8-aza-spiro[4,5]dec-8-yl)-11H-indeno[1,2-c]quinolin-11-one,   9-chloro-6-(4-((piperazin-1-yl) (piperidin-1-yl)methanone))-11H-indeno[1,2-c]quinolin-11-one, and   9-chloro-6-(4-(3-(piperidin-4-yl) propyl) piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one; (4) Dissolve 6,9-dichloro-11H-indeno[1,2-c]quinoline-11-one obtained from step 1 in dimethyl formamide and then add 2-mercaptoethanol followed by catalytic reaction of potassium carbonate at 150° C. for 4 hours. At the end of reaction, pour the mixture into ice water and incubate for 10 to 20 minutes. Finally, recrystallize the precipitate with ethanol to give the compound 6-(2-hydroxy-ethylthio)-9-chloro-11H-indeno[1,2-c]quinolin-11-one; (5) dissolve 6,9-dichloro-11H-indeno[1,2-c]quinoline-11-one obtained from step 1 in dimethyl formamide and then add conc. hydrochloric acid at 150° C. for 24 hours. At the end of reaction, pour the mixture into ice water and incubate for 10 to 20 minutes. Finally, recrystallize the precipitate with ethanol to give the compound 6-hydroxy-9-chloro-11H-indeno[1,2-c]quinolin-11-one; (6) dissolve 6,9-dichloro-11H-indeno[1,2-c]quinoline-11-one obtained from step 1 in methanol then add sodium methoxide at 90° C. for 10 hours. At the end of reaction, cool the mixture and recrystallize the precipitate with ethanol to give the compound 6-methoxy-9-chloro-11H-indeno[1,2-c]quinolin-11-one.   
 
         [0063]    These features and advantages of the present invention will be fully understood and appreciated from the following detailed description of the accompanying Drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0064]      FIG. 1  shows the overview of the chemical reaction for synthesis of various compounds. Reactoin i is NaOAc at 200° C. for 2 hours, reaction ii is POCl3 at 150° C. for 48 hours, reaction iii: (a) SJ-1-3: the reactions of primary amines DMF and DIPEA in a mini-reactor at 150° C. for 2 hours; (b) SJ-4-24: reactions of secondary amines DMF and pyridine in a mini-reactor at 150° C. for 2 hours; (c) SJ-25: add 2-mercaptoethanol/K 2 CO 3 ; (d) SJ-26: add conc. HCl, DMF, reflux 24 hours; (e) SJ-27: NaOMe, MeOH, reflux 8 hours. 
           [0065]      FIG. 2  shows the screening results of 4 compounds selected from SRB assays for use as the Topoisomerase I drugs. 
           [0066]      FIG. 3  shows the TC-XCl (NSC 773972) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0067]      FIG. 4  shows the SJ-1 (NSC 772856) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0068]      FIG. 5  shows the SJ-2 (NSC 771781) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0069]      FIG. 6  shows the SJ-3 (NSC 772864) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0070]      FIG. 7  shows the SJ-6 (NSC 772860) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0071]      FIG. 8  shows the SJ-8 (NSC 771782)) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0072]      FIG. 9  shows the SJ-9 (NSC 772857) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0073]      FIG. 10  shows the SJ-10 (NSC 772862) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0074]      FIG. 11  shows the SJ-12 (NSC 771783) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0075]      FIG. 12  shows the SJ-14 (NSC 772859) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0076]      FIG. 13  shows the SJ-16 (NSC 772861) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0077]      FIG. 14  shows the SJ-20 (NSC 772863) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0078]      FIG. 15  shows the SJ-23 (NSC 772858) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
           [0079]      FIG. 16  shows the SJ-25 (NSC 765596) cytotoxicity in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen. 
       
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0080]    Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs. As used herein, the following terms have the meanings ascribed to them unless specified otherwise. The present invention will now be described more specifically with reference to the following embodiments, which are provided for the purpose of demonstration rather than limitation. 
         [0081]    The term “treatment”, “under treatment” and similar terms refer to the methods which ameliorate, improve, reduce or reverse the patient&#39;s disease or any relevant symptoms caused by the disease, or methods which can prevent the onset of such diseases or any resulting symptoms. 
         [0082]    The term ““pharmaceutically acceptable” is used to describe substances to be used in the composition which must be compatible with other ingredients in the formulation and be harmless to the subject. 
         [0083]    The inventive composition can be prepared into a dosage form for suitable application of the inventive composition by using technology commonly understood by a person skilled in the art through formulating the abovementioned compound with a pharmaceutically acceptable vehicle, wherein the excipients include, but are not limited to, solution, emulsion, suspension, powder, tablet, pill, lozenge, troche, chewing gum, slurry, and other suitable forms. 
         [0084]    The pharmaceutically acceptable vehicle may contain one or several reagents selected from the following list: solvents, emulsifiers, suspending agents, decomposers, binding agents, excipients, stabilizing agents, chelating agents, diluents, gelling agents, preservatives, lubricants, surfactants and other agents suitable for use in the invention. 
         [0085]    In the abovementioned compositions, one or more dissolving aids, buffers, preservatives, colorants, fragrances, flavoring agents and the like, which are commonly used for formulation can be added as desired. 
         [0086]    The term “pharmaceutically acceptable excipients”, include, but are not limited to, polymers, resins, plasticizers, fillers, lubricants, diluents, binders, disintegrants, solvents, co-solvents, surfactants, preservatives, sweetening agents, flavoring agents, pharmaceutical grade dyes or pigments, and viscosity agents. 
         [0087]    The term “pharmaceutical composition” is used to describe solid or liquid compositions in a form, concentration and purity that is suitable for administration in patients (e.g. humans or animals) and can induce desired physiological changes following administration. Pharmaceutical compositions are typically sterile and non-pyrogenic. 
         [0088]    The present invention will now be described more specifically with reference to the following embodiments, which are provided for the purpose of demonstration rather than limitation. The drugs as well as biomaterials used in the invention are all commercially available materials and the sources disclosed below are merely examples. 
         [0089]    General Procedures for Chemical Synthesis 
         [0090]    General procedure A: Synthesis of the compound TC-XCl-1. Mix isatin (0.44 g, 3 mmole), 2-(4-chlorophenyl)acetic acid (0.59 g, 3.47 mmole) and sodium acetate (0.05 g) in a miniclave (200° C.) for 3 hours. Allow cooling of the mixture before addition of acetic acid (10 mL) and collect precipitate by filtration and extraction. Wash the precipitate with acetic acid, water and n-hexane to obtain the intermediate product (TC-XCl). 
         [0091]    Slowly add dried intermediate product (TC-XCl) (0.72 g, 2.4 mmole) to phosphoryl trichloride (20 mL) and allow to reflux at 150° C. for 48 hours. Upon completion of the reaction, allow cooling to room temperature followed by addition of 0° C. ice water. Collect precipitate by filtration and suction and add the collected precipitate to 10% sodium bicarbonate solution (300 mL) for 1 hr with vigorous shaking. Wash with water and recrystallize the crude product with dichloromethane to give the orange compound, TC-XCl-1. 
         [0092]    General procedure B: Synthesis of the compounds SJ-1 and SJ-3. Dissolve 0.3 g TC-XCl-1 (1 mmole) in N,N-dimethylformamide (10 mL) and then add methylamine/N1,N1-diethylethane-1,2-diamine (10 mmole). Catalyze the reaction with 0.5 mL N,N-diisopropylethylamine (2.9 mmole) and place in a miniclave (150° C.) for 4 hours. At the end of reaction, pour the mixture into 100 mL ice water and incubate for 10 to 20 minutes to allow precipitation. Collect the precipitate by filtration and suction and recrystallize the precipitate with ethanol to obtain the compounds SJ-1 and SJ-3. 
         [0093]    General procedure C: Synthesis of the compounds SJ-2, SJ4-24, 26 and 27. Dissolve 0.3 g of TC-XCl-1 (1 mmole) in 10 mL N,N-dimethylformamide and add secondary amine (10 mmole) and catalyze the reaction by adding 0.5 mL pyridine (6.21 mmole) and incubate in a miniclave (150° C.) for 4 hours. At the end of reaction, pour the mixture into 100 mL of ice water and incubate for 10 to 20 minutes to acquire precipitate. Vacuum extraction of the precipitate and recrystallize the precipitate with ethanol to obtain SJ-2 and SJ4-24. 
         [0094]    General procedure D: Synthesis of the compound SJ-25. Dissolve 0.3 g of TC-XCl-1 (1 mmole) in 10 mL N,N-dimethylformamide (10 ml) and add 0.78 g of 2-mercaptoethanol (10 mmole) and catalyze the reaction by adding 0.27 g of potassium carbonate (2 mmole) and incubate in a miniclave (150° C.) for 4 hours. At the end of reaction, pour the mixture into 100 mL of ice water and incubate for 10 to 20 minutes to acquire precipitate. Vacuum extraction of the precipitate and recrystallize the precipitate with ethanol to obtain SJ-25. 
         [0095]    A total of 28 compounds were synthesized ( FIG. 1 ) and are numbered as TC-XCl-1 and SJ-1 through SJ-27 including compound synthesis process, nomenclature, methods for synthesis, molecular formula, molecular weight, melting point, Rf, HRMS, IR, 1H-NMR, and 13C-NMR. The melting point was measured using a Biichi 545 melting point apparatus in our lab and the measurement results are accurate to the first decimal place. In order to ensure consistency, only the integer parts of the numbers were recorded. IR values are determined using Shimadzu FTIR-8300 infrared spectrometer which is located in Department of Pharmacy, National Defense Medical College on the ninth floor. 1H-NMR and 13C-NMR values are measure using the Varian GEMINI-300 (300 MHz) which is located in the basement of National Defense Medical Center. Determination of molecular weights was conducted at in the Department of Chemistry, National Tsing Hua University (Precious Instrument Center of NSC). MAT-95XL HRMS is measured using the high-resolution mass spectrometry (HRMS) (EI) Finnigan/Thermo Quest MAT HRMS in the Department of Chemistry, National Chung Hsing University, and a high-resolution electrospray ionization mass spectrometry HRMS (ESI) FINNIGAN MAT95S in the Department of Chemistry, National Taiwan University. 
       Example 1 
     6,9-Dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1) 
       [0096]    
       
                 
         
             
             
         
       
     
         [0097]    A mixture of isatin 0.44 g (3 mmol), 2-(4-chlorophenyl) acetic acid 0.59 g (3.47 mmol), and sodium acetate (0.05 g) was heated in miniclave at 200° C. for 3 hours (TLC monitoring). Add 10 mL of acetic acid to the mixture after cooling, and collect the precipitate was and wash with H 2 O and n-hexane to get compound TC-XCl (0.72 g, 80%). 
         [0098]    Add 3-(4-chlorophenyl)-2-hydroxyquinoline-4-carboxylic acid (0.72 g, 2.4 mmol) to 20 mL of phosphoryl trichloride and reflux the mixture at 150° C. for 48 hours. After cooling, pour the mixture into ice water (300 mL) at 0° C. Collect the resulting precipitate by filtration and mix with 10% NaHCO 3  solution (300 mL) with vigorous stirring for 1 hr. Wash the resulting precipitate with H 2 O. The crude product was recrystallized from dichloromethane to get orange product TC-XCl-1 (0.22 g, 30.0%). 
         [0099]    Mol. Wt.: 300.1389 (C 16 H 7 Cl 2 NO); Yield: 30.0%; Mp.: 241-243° C. (EtOH); R f : 0.48 (Dichloromethane:Hexane=2:1); IR (KBr) cm −1 : 1719 (C═O); HRMS (ESI) m/z calcd for C 16 H 7 Cl 2 NO + [M]+: 298.9905. Found: [M+H] + =299.9965 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 7.52 (dd, J=8.25, 1.8 Hz, 1H, Ar—H 8 ), 7.62-7.68 (m, 2H, Ar—H 2,10 ), 7.70-7.76 (m, 1H, Ar—H 3 ), 7.97-8.01 (dt, J=7.5, 0.6 Hz, 1H, Ar—H 4 ), 8.10 (d, J=7.8 Hz, 1H, Ar—H 7 ), 8.77-8.80 (m, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 122.97, 124.59, 125.30, 125.69, 129.13, 130.32, 131.70, 135.06, 135.14, 136.19, 136.74, 136.80, 140.15, 145.25, 150.48, 192.804 ( C O). 
       Example 2 
     9-Chloro-6-(methylamino)-11H-indeno[1,2-c]quinolin-11-one (SJ-1) 
       [0100]    
       
                 
         
             
             
         
       
     
         [0101]    Add Methylamine (0.39 mL, 10 mmole) to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added 0.5 mL N,N-diisopropylethylamine (2.9 mmole) to catalyze the reaction. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallize the crude product from hot EtOH to get compound SJ-1 (0.22 g). 
         [0102]    Mol. Wt.: 294.735 (C 17 H 11 ClN 2 O); R f : 0.51 (Dichloromethane:Hexane=2:1); Yield: 75.0%; Mp.: 189-191° C. (EtOH); IR (KBr) cm −1 : 1716 (C═O); HRMS (ESI) m/z calcd for C 17 H 11 ClN 2 O + [M] + : 294.0560. Found: [M+H] + =295.0634 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.01 (s, 3H, N—C H   3 ), 7.41-7.47 (m, 2H, Ar—H 8,10 ), 7.57-7.62 (m, 3H, Ar—H 2,3,7 ), 7.84 (d, J=8.4 Hz, 1H, Ar—H 4 ), 8.68 (d, J=8.1 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 42.22, 120.81, 124.29, 124.93, 124.99, 127.02, 128.13, 130.44, 131.60, 134.33, 135.16, 135.24, 136.59, 141.85, 149.69, 158.14, 194.48 ( C O). 
       Example 3 
     9-Chloro-6-(dimethylamino)-11H-indeno[1,2-c]quinolin-11-one (SJ-2) 
       [0103]    
       
                 
         
             
             
         
       
     
         [0104]    Dimethylamine (0.51 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours anded added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-2 (0.23 g). 
         [0105]    Mol. Wt.: 308.7617 (C 18 H 13 ClN 2 O); R f : 0.51 (Dichloromethane:Hexane=2:1); Yield: 74.5%; Mp.: 193-195° C. (EtOH); IR (KBr) cm −1 : 3407 (N—H stretch), 1718 (C═O); HRMS (EI) m/z calcd for C 18 H 13 ClN 2 O + [M] + : 308.0716. Found: 308.0708 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.04 (s, 6H, —N—(CH 3 ) 2 ), 7.41-7.48 (m, 2H, Ar—H 8,10 ), 7.57-7.63 (m, 3H, Ar—H 2,3,7 ), 7.86 (d, J=8.7 Hz, 1H, Ar—H 4 ), 8.68-8.71 (m, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 42.19, 120.80, 124.27, 124.91, 124.96, 126.99, 128.13, 130.40, 131.57, 134.30, 135.14, 135.22, 136.54, 141.84, 149.70, 158.13, 194.45 ( C O). 
       Example 4 
     6-(2-(Diethylamino)ethylamino)-9-chloro-11H-indeno[1,2-c]quinolin-11-one (SJ-3) 
       [0106]    
       
                 
         
             
             
         
       
     
         [0107]    N 1 ,N 1 -diethylethane-1,2-diamine (1.44 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 115° C. for 24 hours and added N,N-diisopropylethylamine (0.5 mL, 2.9 mmole) as catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-3 (0.07 g). 
         [0108]    Mol. Wt.: 379.8826 (C 22 H 22 ClN 3 O); R f : 0.46 (Dichloromethane:Hexane=2:1); Yield: 17.5%; Mp.: 160-161° C. (EtOH); IR (KBr) cm −1 : 3371 (N—H stretch), 1712 (C═O); HRMS (ESI) m/z calcd for C 22 H 22 ClN 3 O + [M] + : 379.1451. Found: [M+H] + =380.1510 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.11 (t, J=7.2 Hz, 6H, C H   3 ), 2.66 (q, J=7.1 Hz, 4H, —NC H   2 —), 2.84 (t, J=5.7 Hz, 2H, —C H   2 N—), 3.71-3.73 (m, 2H, NHC H   2 —), 6.14 (br, 1H, NH), 7.28-7.33 (m, 1H, Ar—H 8 ), 7.41-7.55 (m, 3H, Ar—H 2,3,10 ), 7.60 (d, J=1.5 Hz, 1H, Ar—H 4 ), 7.70 (d, J=8.7 Hz, 1H, Ar—H 7 ), 8.60 (m, J=8.1 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 12.23, 38.81, 46.92, 51.64, 119.00, 122.48, 124.42, 124.95, 125.40, 126.94, 127.86, 130.53, 134.07, 134.90, 135.08, 135.45, 141.24, 150.68, 152.96, 194.65 ( C O). 
       Example 5 
     9-Chloro-6-(pyrrolidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-4) 
       [0109]    
       
                 
         
             
             
         
       
     
         [0110]    Add 0.83 mL of pyrrolidine (10 mmole) to DMF (10 mL) containing the compound 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1) (0.3 g, 1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added 0.5 mL of pyridine (6.21 mmole) to catalyze the reaction. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-4 (0.15 g). 
         [0111]    Mol. Wt.: 334.7989 (C 20 H 15 N 4 ClN 2 O); R f : 0.51 (Dichloromethane:Hexane=2:1); Yield: 43.6%; Mp.: 149-150° C. (EtOH); IR (KBr) cm −1 : 1718 (C═O); HRMS (ESI) m/z calcd for C 20 H 15 N 4 ClN 2 O + [M] + : 334.0873. Found: [M+H] + =335.0952 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.98 (quin, J=3.6 Hz, 4H, H-3′,4′), 3.56 (t, J=6.6 Hz, 4H, H-2′,5′), 7.33-7.42 (m, 3H, Ar—H 2,8,10 ), 7.54 (td, J=7.5, 1.5 Hz, 2H, Ar—H 3,4 ), 7.76 (d, J=8.4 Hz, 1H, Ar—H 7 ), 8.63 (dd, J=8.4, 0.9 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 25.07, 50.37, 120.39, 124.25, 124.80, 124.96, 126.29, 127.78, 130.33, 130.40, 134.10, 134.83, 135.27, 136.46, 142.50, 149.78, 155.73, 194.65 ( C O). 
       Example 6 
     9-Chloro-6-(piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-5) 
       [0112]    
       
                 
         
             
             
         
       
     
         [0113]    Add 0.99 mL of piperidine (10 mmole) to 10 mL of DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours followed by addition of 0.5 mL of pyridine (6.21 mmole) to catalyze the reaction. Pour the mixture into ice water after reaction and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-5 (0.15 g). 
         [0114]    Mol. Wt.: 348.8255 (C 21 H 17 ClN 2 O); R f : 0.63 (Dichloromethane:Hexane=2:1); Yield: 43.0%; Mp.: 191-192° C. (EtOH); IR (KBr) cm −1 : 1717 (C═O); HRMS (ESI) m/z calcd for C 21 H 17 ClN 2 O + [M] + : 348.1029. Found: [M+H] + =349.1106 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.71 (br, 2H, H- 4′ ), 1.83-1.86 (m, 4H, H- 3′,5′ ), 3.33 (br, 4H, H- 2′,6′ ), 7.43-7.48 (m, 2H, Ar—H 8,10 ), 7.58-7.66 (m, 3H, Ar—H 2,3,4 ), 7.90 (d, J=8.1 Hz, 1H, Ar—H 7 ), 8.70 (d, J=8.7 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 24.37, 26.01, 51.30, 120.81, 124.22, 124.41, 124.83, 127.09, 128.29, 130.24, 131.88, 134.24, 135.01, 135.17, 136.35, 142.05, 149.79, 158.35, 194.38 ( C O). 
       Example 7 
     9-Chloro-6-(4-methylpiperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-6) 
       [0115]    
       
                 
         
             
             
         
       
     
         [0116]    4-methylpiperidine (1.18 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-6 (0.09 g). 
         [0117]    Mol. Wt.: 362.8521 (C 22 H 19 ClN 2 O); R f : 0.61 (Dichloromethane:Hexane=2:1); Yield: 25.4%; Mp.: 190-192° C. (EtOH); IR (KBr) cm −1 : 1718 (C═O); HRMS (ESI) m/z calcd for C 22 H 19 ClN 2 O + [M] + : 362.1186. Found: [M+H] + =363.1260 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.07 (d, J=6 Hz, 3H, —C H   3 ), 1.46-1.60 (m, 3H, —C H   2 —, —C H —), 1.84-1.87 (m, 2H, —C H   2 —), 2.96 (t, J=11.6 Hz, 2H, N—C H   2 —), 3.67-3.71 (m, 2H, N—C H   2 —), 7.44-7.46 (m, 2H, Ar—H 8,10 ), 7.58 (m, 3H, Ar—H 2,3,4 ), 7.82-7.85 (m, 1H, Ar—H 7 ), 8.66-8.69 (m, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 22.07, 30.87, 34.43, 50.69, 120.88, 124.27, 124.46, 124.91, 127.15, 128.31, 130.32, 131.98, 134.33, 135.07, 135.23, 136.44, 142.13, 149.83, 158.25, 194.52 ( C O). 
       Example 8 
     6-(Azepan-1-yl)-9-chloro-11H-indeno[1,2-c]quinolin-11-one (SJ-7) 
       [0118]    
       
                 
         
             
             
         
       
     
         [0119]    Azepane (1.13 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-7 (0.13 g). 
         [0120]    Mol. Wt.: 362.8521 (C 22 H 19 ClN 2 O); R f : 0.69 (Dichloromethane:Hexane=2:1); Yield: 35.8%; Mp.: 146-147° C. (EtOH); IR (KBr) cm −1 : 1712 (C═O); MS (ESI) m/z calcd for C 22 H 19 ClN 2 O + [M] + : 362.1186. Found: [M+H] + =363.2000 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.72-1.75 (m, 4H, —C H   2 —), 1.86 (br, 4H, —C H   2 —), 3.64 (t, J=5.6 Hz, 4H, —N—C H   2 —), 7.40-7.46 (m, 2H, Ar—H 8,10 ), 7.54-7.60 (m, 3H, Ar—H 2,3,4 ), 7.78-7.80 (m, 1H, Ar—H 7 ), 8.68 (dd, J=8.4, 0.6 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 27.96, 28.40, 52.91, 120.48, 124.24, 124.76, 124.89, 126.60, 127.98, 130.30, 131.09, 134.13, 134.97, 135.15, 136.84, 142.54, 149.74, 157.83, 194.62 ( C O). 
       Example 9 
     9-Chloro-6-morpholino-11H-indeno[1,2-c]quinolin-11-one (SJ-8) 
       [0121]    
       
                 
         
             
             
         
       
     
         [0122]    Morpholine (0.86 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-8 (0.16 g). 
         [0123]    Mol. Wt.: 350.7983 (C 20 H 15 aN 2 O 2 ); R f : 0.54 (Dichloromethane:Hexane=2:1); Yield: 47.0%; Mp.: 207-208° C. (EtOH); IR (KBr) cm −1 : 1712 (C═O); HRMS (ESI) m/z calcd for C 20 H 15 ClN 2 O 2   + [M] + : 350.0822. Found: [M+H] + =351.0898 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.41 (t, J=4.5 Hz, 4H, —CĤ 2 —), 3.98 (t, J=4.5 Hz, 4H, —CĤ 2 —), 7.48 (td, J=8.1, 2.1 Hz, 2H, Ar—H 8,10 ), 7.59-7.65 (m, 3H, Ar—H 2,3,4 ), 7.87 (d, J=8.7 Hz, 1H, Ar—H 7 ), 8.69-8.72 (dt, J=8.1, 0.9 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 50.56, 66.98, 121.18, 124.35, 124.43, 125.23, 127.65, 128.51, 130.59, 131.46, 134.42, 135.21, 135.55, 136.80, 141.66, 149.81, 157.31, 194.14 ( C O). 
       Example 10 
     9-Chloro-6-thiomorpholino-11H-indeno[1,2-c]quinolin-11-one (SJ-9) 
       [0124]    
       
                 
         
             
             
         
       
     
         [0125]    Thiomorpholine (1 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-9 (0.27 g). 
         [0126]    Mol. Wt.: 366.8639 (C 20 H 15 ClN 2 O 2 ); R f : 0.33 (Dichloromethane:Hexane=2:1); Yield: 74.3%; Mp.: 228-230° C. (EtOH); IR (KBr) cm −1 : 1711 (C═O); HRMS (ESI) m/z calcd for C 20 H 15 ClN 2 O 2   + [M] + : 366.0594. Found: [M+H] + =367.0664 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 2.91 (t, J=5.1 Hz, 4H, —C H   2 —), 2.69-2.73 (br, 4H, —C H   2 —), 7.45-7.50 (td, J=7.8, 1.8 Hz, 2H, Ar—H 8,10 ), 7.57-7.64 (m, 3H, Ar—H 2,3,4 ), 7.85 (d, J=9.0 Hz, 1H, Ar—H 7 ), 8.68-8.71 (dd, J=8.25, 1.2 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 27.38, 52.36, 121.07, 124.29, 125.19, 127.66, 128.48, 129.44, 130.57, 131.59, 134.40, 135.10, 135.54, 136.87, 141.70, 149.70, 157.66, 194.17 ( C O). 
       Example 11 
     9-Chloro-6-(piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-10) 
       [0127]    
       
                 
         
             
             
         
       
     
         [0128]    piperazine (0.86 g, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-10 (0.17 g). 
         [0129]    Mol. Wt.: 349.8135 (C 20 H 16 ClN 3 O); R f : 0.43 (Dichloromethane:Hexane=2:1); Yield: 47.5%; Mp.: 180-181° C. (EtOH); R (KBr) cm −1 : 3341 (N—H stretch), 1718 (C═O); FIRMS (ESI) m/z calcd for C 20 H 16 ClN 3 O + [M] + : 349.0982. Found: [M+H] + =350.1063 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.16 (t, J=4.8 Hz, 4H, —C H   2 —), 3.36 (br, 4H, —C H   2 —), 7.46-7.49 (m, 2H, Ar—H 8,10 ), 7.62-7.66 (m, 3H, Ar—H 2,3,4 ), 7.87 (d, J=8.7 Hz, 1H, Ar—H 7 ), 8.71 (d, J=8.7 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 46.17, 51.51, 121.05, 124.31, 124.54, 125.11, 127.45, 128.46, 130.48, 131.69, 134.39, 135.16, 135.40, 136.68, 141.88, 149.84, 157.83, 194.37 ( C O). 
       Example 12 
     9-Chloro-6-(2-methylpiperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-11) 
       [0130]    
       
                 
         
             
             
         
       
     
         [0131]    3-methylpiperazine (1.0 g, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-11 (0.06 g). 
         [0132]    Mol. Wt.: 363.8401 (C 21 H 18 ClN 3 O); R f : 0.49 (Dichloromethane:Methanol=2:0.5); Yield: 17.5%; Mp.: 199-200° C. (EtOH); IR (KBr) cm −1 : 3222 (N—H stretch), 1719 (C═O); HRMS (ESI) m/z calcd for C 21 H 18 ClN 3 O + [M] + : 363.1138. Found: [M+H] + =364.1201 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.17 (d, J=6.3 Hz, 3H, —C H   3 ), 2.70 (t, 1H, —C H   2 —), 3.03-3.07 (m, 1H, N—C H —), 3.15-3.19 (m, 3H, —C H   2 —, —C H   2 —NH), 3.60-3.65 (d, J=12.6 Hz, 2H, NH—C H   2 —), 7.44-7.48 (m, 2H, Ar—H 8,10 ), 7.58-7.62 (m, 3H, ArH 2,3,4 ), 7.86 (d, J=8.4 Hz, 1H, Ar—H 7 ), 8.69 (d, J=7.8 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 19.96, 45.98, 50.63, 50.75, 57.67, 120.98, 124.29, 124.47, 125.09, 127.39, 128.41, 130.47, 131.63, 134.37, 135.15, 135.36, 136.65, 141.89, 149.82, 157.56, 194.36 ( C O). 
       Example 13 
     9-Chloro-6-(4-methylpiperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-12) 
       [0133]    
       
                 
         
             
             
         
       
     
         [0134]    1-methylpiperazine (1.11 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[ 1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-12 (0.19 g). 
         [0135]    Mol. Wt.: 363.8401 (C 21 H 18 ClN 3 O); R f : 0.4 (Dichloromethane:Hexane=2:1); Yield: 51.4%; Mp.: 205-207° C. (EtOH); IR (KBr) cm −1 : 3426 (N—H stretch), 1720 (C═O); HRMS (ESI) m/z calcd for C 21 H 18 ClN 3 O + [M] + : 363.1138. Found: [M+H] + =364.1222 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 2.42 (s, 3H, N—C H   3 ), 2.70 (br, 4H, —C H   2 —), 3.43 (br, 4H, N—C H   2 —), 7.44-7.47 (m, 2H, Ar—H 8,10 ), 7.58-7.61 (m, 3H, Ar—H 2,3,4 ), 7.84 (d, J=8.4 Hz, 1H, Ar—H 7 ), 8.67 (d, J=8.1 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 46.38, 49.97, 55.17, 121.00, 124.28, 124.54, 125.07, 127.38, 128.46, 130.45, 131.51, 134.35, 135.13, 135.38, 136.63, 141.84, 149.80, 157.37, 194.29 ( C O). 
       Example 14 
     9-Chloro-6-(4-ethylpiperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-13) 
       [0136]    
       
                 
         
             
             
         
       
     
         [0137]    1-ethylpiperazine (1.27 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-13 (0.07 g). 
         [0138]    Mol. Wt.: 377.8667 (C 22 H 20 ClN 3 O); R f : 0.43 (Dichloromethane:Hexane:Methanol=2:1:0.5); Yield: 19.8%; Mp.: 182-184° C. (EtOH); IR (KBr) cm −1 : 1710 (C═O); HRMS (ESI) m/z calcd for C 22 H 20 ClN 3 O + [M] + : 377.1295. Found: [M+H] + =378.1380 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.19 (t, 3H, J=7.2 Hz, —C H   3 ), 2.57 (q, 2H, J=7.4 Hz, —N—C H   2 —), 3.03 (br, 4H, —C H   2 —), 3.46 (br, 4H, —C H   2 —), 7.43-7.48 (m, 2H, Ar—H 8,10 ), 7.57-7.60 (m, 3H, Ar—H 2,3,4 ), 7.85 (d, J=8.4 Hz, 1H, Ar—H 7 ), 8.69 (dd, J=8.25, 0.9 Hz, 1H, Ar—H 1 );  13 C-NMR (75 MHz, CDCl 3 ) δ (ppm): 12.06, 49.99, 52.69, 52.85, 121.02, 124.30, 124.59, 125.07, 127.36, 128.49, 130.43, 131.53, 134.36, 135.19, 135.38, 136.64, 141.89, 149.84, 15740, 194.32 ( C O). 
       Example 15 
     9-Chloro-6-(4-cyclopentylpiperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-14) 
       [0139]    
       
                 
         
             
             
         
       
     
         [0140]    1-cyclopentylpiperazine (1.27 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-14 (0.16 g). 
         [0141]    Mol. Wt.: 417.9306 (C 25 H 24 ClN 3 O); R f : 0.46 (Dichloromethane:Hexane:Methanol=2:1:0.5); Yield: 37.3%; Mp.: 183-184° C. (EtOH); IR (KBr) cm −1 : 1716 (C═O); HRMS (ESI) m/z calcd for C 25 H 24 ClN 3 O + [M] + : 417.1608. Found: [M+H] + =418.1689 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.19 (t, 3H, J=7.2 Hz, —C H   3 ), 2.57 (q, 2H, J=7.4 Hz, N—C H   2 —), 3.03 (br, 4H, —C H   2 —), 3.46 (br, 4H, —C H   2 —), 7.43-7.48 (m, 2H, Ar—H 8,10 ), 7.57-7.63 (m, 3H, Ar—H 2,3,4 ), 7.85 (d, J=8.7 Hz, 1H, Ar—H 7 ), 8.69 (d, J=8.1 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 24.32, 30.67, 50.12, 52.36, 67.87, 120.99, 124.28, 124.61, 125.05, 127.31, 128.50, 130.40, 131.56, 134.36, 135.19, 135.32, 136.58, 141.94, 149.85, 157.48, 194.40 ( C O). 
       Example 16 
     9-Chloro-6-(4-(piperidin-1-yl)piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-15) 
       [0142]    
       
                 
         
             
             
         
       
     
         [0143]    1-(piperidin-4-yl)piperidine (1.68 g, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-15 (0.25 g). 
         [0144]    Mol. Wt.: 431.9571 (C 26 H 26 ClN 3 O); R f : 0.51 (Dichloromethane:Hexane:Methanol=2:1:0.5); Yield: 57.3%; Mp.: 174-175° C. (EtOH); IR (KBr) cm −1 : 1718 (C═O); HRMS (ESI) m/z calcd for C 26 H 26 ClN 3 O + [M] + : 431.1764. Found: [M+H] + =432.1822 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.48-1.50 (m, 2H, —C H   2 —), 1.63-1.65 (m, 2H, —C H   2 —), 1.72-1.85 (m, 4H, —C H   2 —), 2.08 (d, J=11.4 Hz, 2H, —C H   2 —), 2.38-2.46 (m, 1H, —C H   2 —), 2.60 (s, 4H, —C H —), 2.91-3.02 (m, 2H, —C H   2 —), 3.76 (d, J=12.3 Hz, 2H, —C H   2 —), 7.41-7.45 (m, 2H, Ar—H 8,10 ), 7.55-7.61 (m, 3H, Ar—H 2,3,4 ), 7.82 (d, J=8.4 Hz, 1H, Ar—H 7 ), 8.66 (d, J=7.8 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 24.99, 26.61, 28.77, 50.17, 50.85, 62.51, 120.98, 124.27, 124.42, 124.96, 127.26, 128.36, 130.34, 131.86, 134.37, 135.08, 135.32, 136.45, 141.99, 149.80, 157.82, 194.39 ( C O). 
       Example 17 
     9-Chloro-6-(4-phenylpiperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-16) 
       [0145]    
       
                 
         
             
             
         
       
     
         [0146]    1-phenylpiperazine (1.53 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-16 (0.22 g). 
         [0147]    Mol. Wt.: 425.9095 (C 26 H 20 ClN 3 O); R f : 0.91 (Dichloromethane:Hexane:Methanol=3:1:0.5); Yield: 51.7%; Mp.: 193-194° C. (EtOH); IR (KBr) cm −1 : 1714 (C═O); HRMS (ESI) m/z calcd for C 26 H 20 ClN 3 O + [M] + : 425.1295. Found: [M+H] + =426.1370 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.47 (br, 4H, —C H   2 —), 3.57 (br, 4H, —C H   2 —), 6.93 (t, J=7.2 Hz, 1H, Ar—H), 7.04 (d, J=7.8 Hz, 2H, Ar—H), 7.30-7.36 (m, 2H, Ar—H), 7.45-7.51 (m, 2H, Ar—H 8,10 ), 7.58-7.70 (m, 3H, Ar—H 2,3,4 ), 7.88 (d, J=7.8 Hz, 1H, Ar—H 7 ), 8.72 (d, J=8.1 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 49.44, 50.16, 116.66, 120.53, 121.14, 124.32, 124.52, 125.21, 127.60, 128.49, 129.57, 130.56, 131.60, 134.43, 135.16, 135.49, 136.68, 141.74, 149.78, 151.65, 157.41, 194.30 ( C O). 
       Example 18 
     6-(4-Benzylpiperazin-1-yl)-9-chloro-11H-indeno[1,2-c]quinolin-11-one (SJ-17) 
       [0148]    
       
                 
         
             
             
         
       
     
         [0149]    1-benzylpiperazine (1.74 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-17 (0.18 g). 
         [0150]    Mol. Wt.: 439.9361 (C 27 H 22 ClN 3 O); R f : 0.37 (Dichloromethane:Hexane=2:1); Yield: 40.9%; Mp.: 178-180° C. (EtOH); IR (KBr) cm −1 : 1718 (C═O); HRMS (ESI) m/z calcd for C 27 H 22 ClN 3 O + [M] + : 439.1451. Found: [M+H] + =440.1503 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 2.73 (br, 4H, —C H   2 —), 3.41 (br, 4H, —C H   2 —), 3.65 (s, 2H, —C H   2 —) 7.28-7.47 (m, 7H, Ar—H 8,10 , Ar—H), 7.57-7.63 (m, 3H, Ar—H 2,3,4 ), 7.84 (d, J=8.7 Hz, 1H, Ar—H 7 ), 8.68 (d, J=7.05 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 50.11, 53.21, 63.34, 120.97, 124.26, 124.60, 125.04, 127.34, 127.50, 128.42, 128.64, 129.40, 130.42, 131.61, 134.35, 135.11, 135.30, 136.53, 138.46, 141.83, 149.78, 157.55, 194.38 ( C O). 
       Example 19 
     9-Chloro-6-(4-(2-fluorophenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-18) 
       [0151]    
       
                 
         
             
             
         
       
     
         [0152]    1-(2-fluorophenyl)piperazine (1.58 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-18 (0.18 g). 
         [0153]    Mol. Wt.: 443.9 (C 26 H 19 ClN 3 O); R f : 0.46 (Dichloromethane:Hexane=2:1); Yield: 40.6%; Mp.: 182-183° C. (EtOH); IR (KBr) cm −1 : 1715 (C═O); HRMS (ESI) m/z calcd for C 26 H 19 ClN 3 O + [M] + : 443.1201. Found: [M+H] + =444.1269 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.37 (br, 4H, —C H   2 —), 3.59 (br, 4H, —C H   2 —), 7.00-7.12 (m, 4H, Ar—H), 7.44-7.50 (m, 2H, Ar—H 8,10 ), 7.59-7.68 (m, 3H, Ar—H 2,3,4 ), 7.88 (d, J=8.1 Hz, 1H, Ar—H 7 ), 8.71 (d, J=8.1 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 50.27, 50.63, 116.47, 116.75, 119.48, 121.09, 123.06, 123.17, 124.31, 124.53, 124.80, 124.86, 125.17, 127.54, 128.49, 130.54, 131.55, 134.40, 135.16, 135.45, 141.76, 149.78, 157.37, 194.29 ( C O). 
       Example 20 
     9-Chloro-6-(4-(2-methoxyphenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-19) 
       [0154]    
       
                 
         
             
             
         
       
     
         [0155]    1-(2-methoxyphenyl)piperazine (1.38 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-19 (0.17 g). 
         [0156]    Mol. Wt.: 455.9355 (C 27 H 22 ClN 3 O 2 ); R f : 0.38 (Dichloromethane:Hexane=2:1); Yield: 37.3%; Mp.: 129-131° C. (EtOH); IR (KBr) cm −1 : 1714 (C═O); HRMS (ESI) m/z calcd for C 27 H 22 ClN 3 O 2   + [M] + : 455.1401. Found: [M+H] + =456.1473 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.36 (br, 4H, —C H   2 —), 3.60 (br, 4H, —C H   2 —), 3.90 (s, 3H, —O—C H   3 ), 6.91-7.07 (m, 4H, Ar—H), 7.47 (t, J=7.5 Hz, 2H, Ar—H 8,10 ), 7.59-7.63 (m, 2H, Ar—H 2,3 ), 7.68 (d, J=7.8 Hz, 1H, Ar—H 4 ), 7.87 (d, J=8.1 Hz, 1H, Ar—H 7 ), 8.70 (d, J=8.4 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 50.39, 50.75, 55.75, 112.15, 118.68, 121.03, 121.49, 123.55, 124.28, 124.61, 125.09, 127.40, 128.47, 130.46, 131.58, 134.36, 135.15, 135.36, 136.61, 141.66, 141.85, 149.81, 152.86, 157.53, 194.38 ( C O). 
       Example 21 
     9-Chloro-6-(4-(3-methoxyphenyl)piperazin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-20) 
       [0157]    
       
                 
         
             
             
         
       
     
         [0158]    1-(3-methoxyphenyl)piperazine (1.73 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as catalyst. After reaction, poured it into ice water and filtered to gain crude. Recrystallized from hot EtOH to gain compound SJ-20 (0.39 g). 
         [0159]    Mol. Wt.: 455.9355 (C 27 H 22 ClN 3 O 2 ); R f : 0.43 (Dichloromethane:Hexane=2:1); Yield: 85.9%; Mp.: 189-191° C. (EtOH); IR (KBr) cm −1 : 1723 (C═O); HRMS (ESI) m/z calcd for C 27 H 22 ClN 3 O 2   + [M] + : 455.1401. Found: [M+H] + =456.1464 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.46 (br, 4H, —C H   2 —), 3.55 (br, 4H, —C H   2 —), 3.83 (s, 3H, —O—C H   3 ), 6.50 (m, J=8.1 Hz, 1H, Ar—H), 6.57 (s, 1H, Ar—H), 6.65 (d, J=8.4 Hz, 1H, Ar—H), 7.22 (d, J=8.1 Hz, 1H, Ar—H), 7.44-7.51 (m, 2H, Ar—H 8,10 ), 7.60-7.68 (m, 3H, Ar—H 2,3,4 ), 7.88 (d, J=8.1 Hz, 1H, Ar—H 7 ), 8.71 (d, J=7.2 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 49.36, 50.08, 55.46, 103.25, 105.29, 109.41, 121.14, 124.31, 124.50, 125.18, 127.60, 128.49, 130.25, 130.56, 131.56, 134.42, 135.15, 135.49, 136.68, 141.70, 149.77, 153.00, 157.35, 161.17, 194.23 ( C O). 
       Example 22 
     9-Chloro-6-(4-(1-methylpiperidin-4-yl)piperazin-1-yl)-11H-inden o[1,2-c]quinolin-11-one (SJ-21) 
       [0160]    
       
                 
         
             
             
         
       
     
         [0161]    1-(1-methylpiperidin-4-yl)piperazine (1.83 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-21 (0.14 g). 
         [0162]    Mol. Wt.: 446.9718 (C 26 H 27 ClN 4 O); R f : 0.90 (Dichloromethane:Hexane:Methanol=2:1:0.5); Yield: 30.4%; Mp.: 208-209° C. (EtOH); IR (KBr) cm −1 : 1710 (C═O); HRMS (ESI) m/z calcd for C 26 H 27 ClN 4 O + [M] + : 446.1873. Found: [M+H] + =447.1944 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.64-1.72 (m, 2H, —C H   2 —), 1.88 (d, J=10.5 Hz, 1H, —C H   2 —), 1.95-2.03 (m, 2H, —C H   2 —), 2.29 (s, 4H, —C H —, —C H   3 ), 2.82 (br, 4H, —C H   2 —), 2.95 (d, J=9.6 Hz, 1H, Ar—H 1 ), 3.40 (br, 4H, —C H   2 —), 6.47-6.50 (m, 1H, Ar—H), 6.57 (s, 1H, Ar—H), 6.65 (d, J=8.4 Hz, 1H, Ar—H), 7.22 (d, J=8.1 Hz, 1H, Ar—H), 7.42-7.47 (m, 2H, Ar—H 8,10 ), 7.57-7.61 (m, 3H, Ar—H 2,3,4 ), 7.84 (d, J=8.4 Hz, 1H, Ar—H 7 ), 8.68 (d, J=7.8 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 28.54, 46.34, 49.24, 50.49, 55.62, 61.83, 120.96, 124.27, 124.61, 125.04, 127.31, 128.45, 130.40, 131.54, 134.33, 135.15, 135.31, 136.55, 141.89, 149.81, 157.49, 194.38 ( C O). 
       Example 23 
     9-Chloro-6-(4-(1,4-dioxa-8-azaspiro[4,5]dec-8-yl)-11H-indeno[1, 2-c]quinolin-11-one (SJ-22) 
       [0163]    
       
                 
         
             
             
         
       
     
         [0164]    1,4-dioxa-8-azaspiro[4,5]dec-8-yl (1.29 mL, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-22 (0.23 g). 
         [0165]    Mol. Wt.: 406.8616 (C 23 H 19 ClN 2 O 3 ); R f : 0.34 (Dichloromethane:Hexane=2:1); Yield: 56.0%; Mp.: 218-219° C. (EtOH); IR (KBr) cm −1 : 1718 (C═O); HRMS (ESI) m/z calcd for C 23 H 19 ClN 2 O 3   + [M] + : 406.1084. Found: [M+H] + =407.1154 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.98 (t, J=5.7 Hz, 4H, —C H   2 —), 3.51 (br, 4H, —N—C H   2 —), 4.04 (s, 4H, —O—C H   2 —), 7.46 (td, J=8.7, 2.1 Hz, 2H, Ar—H 8,10 ), 7.57-7.62 (m, 3H, Ar—H 2,3,4 ), 7.83 (d, J=8.7 Hz, 1H, Ar—H 7 ), 8.69 (dd, J=8.4, 0.9 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 35.00, 48.35, 64.66, 107.31, 120.98, 124.25, 125.06, 127.32, 128.41, 130.42, 131.65, 134.38, 135.09, 135.36, 136.57, 141.97, 149.74, 157.34, 194.43 ( C O). 
       Example 24 
     9-Chloro-6-(4-((piperazin-1-yl)(piperidin-1-yl)methanone)-11H-indeno[1,2-c]quinolin-11-one (SJ-23) 
       [0166]    
       
                 
         
             
             
         
       
     
         [0167]    (piperazin-1-yl)(piperidin-1-yl)methanone (1.00 g, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[ 1,2-c]quinolin-11-one (TC-XCl-1) (1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-23 (0.22 g). 
         [0168]    Mol. Wt.: 460.9553 (C 26 H 25 ClN 4 O 2 ); R f : 0.17 (Dichloromethane:Hexane=2:1); Yield: 46.9%; Mp.: 266-267° C. (EtOH); IR (KBr) cm −1 : 1718, 1647 (C═O stretch); HRMS (ESI) m/z calcd for C 23 H 19 ClN 2 O 3   + [M] + : 460.1666. Found: [M+H] + =461.1739 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.63 (s, 2H, —C H   2 —), 3.28-3.47 (m, 16H, —C H   2 —), 7.42-7.49 (m, 2H, Ar—H 8,10 ), 7.57-7.61 (m, 3H, Ar—H 2,3,4 ), 7.82 (d, J=8.4 Hz, 1H, Ar—H 7 ), 8.69 (d, J=7.8, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 24.86, 25.97, 47.12, 47.99, 49.99, 121.16, 124.32, 124.47, 125.20, 127.65, 128.39, 130.58, 131.62, 134.49, 135.09, 135.54, 136.68, 141.56, 149.69, 157.36, 164.84 ( C O), 194.20 ( C O). 
       Example 25 
     9-Chloro-6-(4-(3-(piperidin-4-yl)propyl)piperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-one (SJ-24) 
       [0169]    
       
                 
         
             
             
         
       
     
         [0170]    4-(3-(piperidin-4-yl)propyl)piperidine (2.10 g, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1) (1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added pyridine (0.5 mL, 6.21 mmole) as the catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-24 (0.04 g). 
         [0171]    Mol. Wt.: 474.0369 (C 29 H 32 ClN 3 O); R f : 0.41 (Dichloromethane:Hexane=2:1); Yield: 8.4%; Mp.: 149-151° C. (EtOH); IR (KBr) cm −1 : 1718 (C═O); HRMS (ESI) m/z calcd for C 29 H 32 ClN 3 O [M] + : 473.2234. Found: [M+H] + =474.2318 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 1.07-1.46 (m, 12H, —C H   2 —, —C H —), 1.66-1.91 (m, 4H, —C H   2 —), 2.54-2.62 (m, 2H, N—C H   2(axial) —), 2.90-2.94 (m, 2H, N—C H   2(axial) —), 3.06 (d, J=12 Hz, 2H, N—C H   2(equatorial) —), 3.70 (d, J=12.3 Hz, 2H, N—C H   2(equatorial) —), 7.41-7.47 (m, 2H, Ar—H 8,10 ), 7.56-7.61 (m, 3H, Ar—H 2,3,4 ), 7.84 (d, J=8.4 Hz, 1H, Ar—H 7 ), 8.68 (d, J=8.1, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 23.81, 32.58, 33.95, 35.88, 36.49, 37.04, 37.65, 47.07, 50.75, 120.89, 124.27, 124.44, 124.92, 127.15, 128.31, 130.32, 131.96, 134.33, 135.08, 135.23, 136.43, 142.12, 149.83, 158.22, 194.52 ( C O). 
       Example 26 
     6-(2-Hydroxyethylthio)-9-chloro-11H-indeno[1,2-c]quinolin-11-one (SJ-25) 
       [0172]    
       
                 
         
             
             
         
       
     
         [0173]    2-mercaptoethanol (0.78 g, 10 mmole) was added to 10 mL DMF containing 0.3 g of 6,9-dichloro-11H-indeno[1,2-c]quinolin-11-one (TC-XCl-1)(1 mmol). The mixture was heated while stirring at 150° C. for 4 hours and added potassium carbonate (0.27 g, 2 mmol) as catalyst. Pour the mixture into ice water after the reaction is completed and filter to get the crude product. Recrystallized from hot EtOH to get compound SJ-25 (0.33 g). 
         [0174]    Mol. Wt.: 341.8114 (C 18 H 12 ClNO 2 S); R f : 0.23 (Dichloromethane:Hexane=2:1); Yield: 95.0%; Mp.: 169-170° C. (EtOH); IR (KBr) cm −1 : 1718 (C═O); HRMS (EI) m/z calcd for C 18 H 12 ClNO 2 S + [M] + : 341.0277. Found: 341.0287 (error&lt;0.3%);  1 H-NMR (300 MHz, CDCl 3 ) δ (ppm): 3.66 (t, J=5.4 Hz, 2H, —S—C H   2 —), 4.11 (t, J=5.25 Hz, 2H, —C H   2 —OH), 4.34 (br, 1H, O H ), 7.47 (dd, J=8.4, 2.1 Hz, 1H, Ar—H 8 ), 7.53 (td, J=8.4, 1.5 Hz, 1H, Ar—H 2 ), 7.61 (d, J=2.1 Hz, 1H, Ar—H 10 ), 7.65 (td, J=8.4, 1.5 Hz, 1H, Ar—H 3 ), 7.87 (d, J=8.1 Hz, 1H, Ar—H 4 ), 7.92 (d, J=8.1 Hz, 1H, Ar—H 7 ), 8.72 (d, J=8.4 Hz, 1H, Ar—H 1 );  13 C-NMR (300 MHz, CDCl 3 ) δ (ppm): 34.05, 63.23, 121.54, 124.64, 125.36, 125.83, 127.90, 128.79, 131.14, 134.11, 134.61, 135.02, 136.08, 136.70, 140.76, 149.91, 155.11, 193.79 ( C O). 
       Example 27 
     6-Hydroxy-9-chloro-11H-indeno[1,2-c]quinolin-11-one (SJ-26) 
       [0175]    
       
                 
         
             
             
         
       
     
         [0176]    Add 0.30 g of TC-XCl-1 (1.0 mmol) to 2 ml of 36% HCl and allow to reflux in DMF (20 mL) at 150° C. for 24 hours. Pour the mixture into ice water and incubate for 10 to 20 minutes. The precipitate collected at this stage is subjected to crystallization by ethanol to get the red compound SJ-26 (0.16 g, 57%). 
         [0177]    Mol. Wt.: 281.6950 (C 16 H 8 ClNO 2 ); Yield: 57%; Mp.: 380° C.; HRMS (ESI) m/z calcd for C 16 H 8 NO 2 Cl [M] + : 281.0244. Found: [M+H] + =282.0322, [M−H] − 280.0178; [M−H] − 280.0244; 1 H NMR (300 MHz, CDCl3) 7.29 (1H, td, J=7.5, 1.2 Hz, Ar—H2), 7.40 (1H, d, J=8.4 Hz, Ar—H9), 7.54-7.65 (3H, m, Ar—H3,7,8), 7.93 (1H, d, J=7.5 Hz, Ar—H4), 8.37 (1H, d, J=7.8 Hz, Ar—H1), 12.38 (br, 1H, —OH);  1 H NMR (400 MHz, DMSO-d6): δ ppm 7.30 (1H, t, J=7.6 Hz, Ar—H), 7.40 (1H, d, J=8.0 Hz, Ar—H), 7.56 (1H, t, J=7.6 Hz, Ar—H), 7.61 (1H, s, Ar—H), 7.63 (1H, d, J=7.6 Hz, Ar—H), 7.93 (1H, d, J=7.6 Hz, Ar—H), 8.37 (1H, d, J=8.4 Hz, Ar—H), 12.42 (1H, br, —OH);  13 C NMR (100 MHz, DMSO-d6): 6 ppm 115.12, 116.39, 123.91, 124.41, 125.02, 131.62, 133.69, 134.33, 134.82, 135.68, 136.68, 140.78, 141.10, 159.20, 194.44. 
       Example 28 
     6-Methoxy-9-chloro-11H-indeno[1,2-c]quinolin-11-one (SJ-27) 
       [0178]    
       
                 
         
             
             
         
       
     
         [0179]    Slowly added methanol containing 1.08 g of sodium methoxide (20 mmol) to TC-XCl-1/methanol (10 ml) and incubate for 10 minutes and allow to reflux in DMF (20 mL) at 90° C. for 10 hours (TLC monitored). After cooling, use a rotary evaporator to remove and filter the solvent and wash with alcohol and n-hexane to get compound SJ-27. 
         [0180]    Mol. Wt.: 295.7220 (C 17 H 10 ClNO 2 ); R f : 0.52 (CH 2 Cl 2 : n-hexane=1:1); Yield: 60%; Mp 259-261° C. (EtOH).  1 H NMR (400 MHz, CDCl 3 ): δ (ppm) 4.24 (3H, s, —OCH 3 ), 7.44 (1H, dd, J=8.0 Hz, 2.0 Hz, Ar—H), 7.47 (1H, td, J=7.6 Hz, 1.2 Hz, Ar—H), 7.59 (1H, d, J=2.0 Hz, Ar—H), 7.62 (1H, td, J=8.0 Hz, 1.6 Hz, Ar—H), 7.75 (1H, d, J=7.6 Hz, Ar—H), 7.85 (1H, d, J=8.4 Hz, Ar—H), 8.67 (1H, dd, J=8.0 Hz, 1.2 Hz, Ar—H).  13 C NMR (100 MHz, CDCl 3 ): δ (ppm) 53.92, 120.66, 124.09, 124.86, 125.03, 126.68, 127.48, 129.08, 130.25, 134.31, 134.51, 135.16, 136.14, 140.25, 148.79, 158.13, 193.88 (C═O). HRMS (ESI) calcd for C 17 H 10 NO 2 Cl [M] + 295.0400. found [M+H] + 296.0482. 
         [0181]    Pharmacological Activity Assay 
         [0182]    In pharmacological tests, compounds synthesized chemically including TC-XCl-1 and SJ-1 through SJ-27 (a total of 28 drugs) are subjected to the following pharmacological activity tests: (1) SRB assay, (2) Topoisomerase I Drug Screening Test, and (3) cytotoxicity assays conducted by NCI on the 16 screened compounds in 55 to 60 cancer cell lines. 
       Example 29 
     Sulforhodamine B (SRB) Assay 
       [0183]    Add 5% Fetal Bovine Serum (FBS) to 96-well plate and fix the cells with 10% TCA after 24 hours of incubation and add the compound (T 0 ). Add DMSO and culture for another 48 hours and the cells are fixed in 0.4% (W/V), 10% TCA and SRB, and stained with 1% acetic acid. Excess SRB is washed off by 1% acetic acid and cells stained with SRB are dissolved in 10 mmol/L Trizma base. The absorbance is measured at 515 nm. The treatment time is 0 (T 0 ), control growth (C) and the increase of the compound (Tx) in the cells are shown below and are used to calculate the increase of the concentration of the compound in percentage. Growth inhibition (GI %) is calculated using the following formula 100−[(T X −T 0 )/(C−T 0 )]×100. The 50% growth inhibition concentration (IC 50 ) is used to confirm the concentration of compound and thus results in 50% reduction of the treated cells which control the amount of total protein. 
         [0184]    This part of experimental results are SRB assays measuring cytotoxicity of the 26 synthesized compounds against human PC-3 cells and are summarized in Table 1 and 2. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 The SRB assay results (I) 
               
             
          
           
               
                   
                 Compound 
                 IC 50  (μM) 
               
               
                   
                   
               
             
          
           
               
                   
                 TC-XCl-1 
                 &gt;15 
               
               
                   
                 SJ-2 
                 4.34 
               
               
                   
                 SJ-8 
                 &gt;10 
               
               
                   
                 SJ-25 
                 &gt;10 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 The SRB assay results (II) 
               
             
          
           
               
                   
                   
                 GI % 
                 Tox- 
               
               
                   
                   
                 (10 
                 icity 
               
               
                 Compd. 
                 —R 
                 μM) 
                 (%) 
               
               
                   
               
             
          
           
               
                 SJ-1 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 52.8  
               
               
                   
               
               
                 SJ-3 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 55.6  
               
               
                   
               
               
                 SJ-4 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 47.2  
               
               
                   
               
               
                 SJ-5 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 22.2  
               
               
                   
               
               
                 SJ-6 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 89.81 
                 0  
               
               
                   
               
               
                 SJ-7 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 41.7  
               
               
                   
               
               
                 SJ-9 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 33.3  
               
               
                   
               
               
                 SJ-10 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 47.2  
               
               
                   
               
               
                 SJ-11 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 64.9  
               
               
                   
               
               
                 SJ-12 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 39.4 
                 0  
               
               
                   
               
               
                 SJ-13 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 29.7  
               
               
                   
               
               
                 SJ-14 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 96.26 
                 0  
               
               
                   
               
               
                 SJ-15 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 98.83 
                 0  
               
               
                   
               
               
                 SJ-16 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 65.91 
                 0  
               
               
                   
               
               
                 SJ-17 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 73.53 
                 0  
               
               
                   
               
               
                 SJ-18 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 85.48 
                 0  
               
               
                   
               
               
                 SJ-19 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 8.5 
               
               
                   
               
               
                 SJ-20 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 98.05 
                 0  
               
               
                   
               
               
                 SJ-21 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 66  
               
               
                   
               
               
                 SJ-22 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 42.6  
               
               
                   
               
               
                 SJ-23 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 43  
               
               
                   
               
               
                 SJ-24 
                 
                   
                             
                     
                         
                         
                     
                   
                 
                 100 
                 63.8  
               
               
                   
               
             
          
         
       
     
       Example 30 
     Topoisomerase I Drug Screening 
       [0185]    Four compounds are selected (SJ-2, SJ-3, SJ-11 and SJ-24) and are used in SRB assays for examination of their cytotoxicity effects against PC-3 cells based on the following principles. 
         [0186]    TopoGEN Topoisomerase I Drug Screening Kit comprises necessary reagents for examining whether the compound has inhibition effects on topoisomerase I (Topo I). This kit can detect compounds utilizing two different mechanisms for inhibition of Top I, the first type inhibits enzyme activity and is called catalytic inhibitory compounds (CICs) and the second type stimulates stable formation of the drug-Top I-DNA cleavage complex and is referred to interfacial poisons (IFPs). Though CICs affect various levels of the enzyme, such as inhibition of the interaction between Topo I and DNA, which is non-specific, but high concentration of salts or polyamines are strong CICs. IFPs, on the other hand, inhibits ligation between nicked DNA. Camptothecin (CPT) and its derivatives are IFPs and are used as positive control in this kit. Under normal conditions, the mechanism of Topo I allows Topo I to enter a breakage/resealing DNA cycle. The cleavage stage during the process is very short and cannot be detected, whereas IFPs, such as integration of Camptothecin into the cleavage complex which leads to interruption of the resealing step and consequently leave the DNA in the nicked (ss break) form and linked to Topo I at the 5′ end of the nick on the DNA by covalent bonds while 3′ end is free. This kit utilizes circular supercoiled plasmid DNA (pHOT1) as the matrix. Topo I relaxes DNA and makes the DNA circular and prevents formation of nicked DNA. Following addition of the drug CPT, proteinase K will denature Topo I and produce nicked (nicked and unsealed) DNA, and this step is necessary for determination of unligated plasmid. If the tested compounds are CICs which can effectively inhibit enzyme activity, no relaxed DNA will be detected in the experiment. 
         [0187]    Based on the results obtained from SRB assays, preliminary tests were conducted to examine the inhibition effects of the four compounds with better drug efficacy, SJ-2, SJ-3, SJ-11 and SJ-24, at the concentrations of 25 μM and 100 μM and the control group camptothecin (CPT) at 100 μM, in duplicate. The results indicate that SJ-11 is more effective than CPT in inhibition of topoisomerase I at the concentration of 25 μM ( FIG. 2 ). The solubility of the four compounds in DMSO is poor, SJ-2&lt;SJ-24&lt;SJ-3&lt;SJ-11, and therefore it is estimated and this is the reason why the three compounds which have previously proven to be effective against PC-3 cell line by SRB assays are ineffective in this experiment. 
       Example 31 
     National Cancer Institute Cancer Cell Cytotoxicity Assay 
       [0188]    The test results shown in this section are the compound cytotoxicities in vitro against cancer cell lines National Cancer Institute (NCI)&#39;s anticancer drug screen and 16 (TC-XLC-1, SJ-1, SJ-2, SJ-3, SJ-6, SJ-8, SJ-9, SJ-10, SJ-12, SJ-14, SJ-16, SJ-20, SJ-23, SJ-25, SJ-26 and SJ-27) were selected from the original 28 compounds screened. In the first stage, cytotoxicity of the 16 compounds at the concentration of 10 μM was conducted on 55 to 60 cell lines and SRB assay was performed after 48 hours of incubation. The results are shown in  FIGS. 3 to 16  and Tables 3 to 7 and are represented by growth percentage. The mean of the growth percentage of all tested cell lines in a group is deducted from the obtained results and is used for determination of the cytotoxicity effect of that particular compound in the tested cancer cell line. 
         [0189]    Two compounds SJ-3 and SJ-10 were found to have potential cytotoxicity and were subjected to the cytotoxicity tests at 5 different concentrations in the second stage. From the results, compounds SJ-3 (NSC 772864) and SJ-10 (NSC 772862) were selected by NCI for a five-dose level screening test and the mean growth percentage of the 60 cancer cell lines for the two compounds are 62.4 and −14.37, respectively. Preliminary analysis of the test results of the 16 compounds selected in the first stage suggests that substitution of the replacement functional group at site 6 of TC-XCl-1 induces more significant selective inhibition effect in breast cancer MCF-7 cell line. A summary of the NCI data provides information on the inhibition effect of various compound in different cancer cell lines ( FIGS. 3 to 16  and Tables 3 to 8). For example, compound TC-XCl-1 can inhibit the growth of 9 cancer cell lines including leukemia and breast cancer cells, whereas compounds SJ-1 and SJ-2 are more effective in breast cancer cell line and compound SJ-10 show preferable inhibition effects in leukemia and colon cancer cells. Table 9 indicates the GI 50 , TGI and LC 50  of the NCI data of TC-XCl, SJ-3 and SJ-10 NCI. 
         [0190]    Many changes and modifications in the above described embodiment of the invention can, of course, be carried out without departing from the scope thereof. Accordingly, to promote the progress in science and the useful arts, the invention is disclosed and is intended to be limited only by the scope of the appended claims. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 TC-XCl-1, SJ-1 and SJ-2 data collected from NCI 
               
             
          
           
               
                   
                   
                 TC-XCL-1 
                 SJ-1 
                 SJ-2 
               
               
                 Compound No. 
                   
                 NSC  
                 NSC  
                 NSC  
               
               
                 NCI No. 
                   
                 763969 
                 772856 
                 771781 
               
               
                   
               
             
          
           
               
                 Leukemia 
                 CCRF-CEM 
                 64.86 
                 101.50 
                 92.13 
               
               
                   
                 HL-60 (TB) 
                 102.00 
                 102.75 
                 95.49 
               
               
                   
                 K-562 
                 102.16 
                 90.99 
                 88.81 
               
               
                   
                 MOLT-4 
                 70.83 
                 93.26 
                 88.92 
               
               
                   
                 RPMI-8226 
                 92.83 
                 91.82 
                 88.05 
               
               
                   
                 SR 
                 65.85 
                 91.67 
                 86.12 
               
               
                 Non-Small Cell 
                 A549/ATCC 
                 108.98 
                 96.83 
                 98.85 
               
               
                 Lung Cancer 
                 EKVX 
                 79.27 
                 N.T. 
                 N.T. 
               
               
                   
                 HOP-62 
                 94.89 
                 87.10 
                 78.02 
               
               
                   
                 HOP-92 
                 71.94 
                 N.T. 
                 44.26 
               
               
                   
                 NCI-H226 
                 91.86 
                 92.19 
                 84.79 
               
               
                   
                 NCI-H23 
                 79.30 
                 86.83 
                 82.62 
               
               
                   
                 NCI-H322M 
                 95.38 
                 80.85 
                 78.83 
               
               
                   
                 NCI-H460 
                 98.68 
                 84.38 
                 94.17 
               
               
                   
                 NCI-H522 
                 89.37 
                 90.50 
                 88.97 
               
               
                 Colon Cancer 
                 COLO 205 
                 99.18 
                 66.47 
                 100.97 
               
               
                   
                 HCC-2998 
                 98.52 
                 57.51 
                 81.50 
               
               
                   
                 HCT-116 
                 105.87 
                 88.31 
                 98.57 
               
               
                   
                 HCT-15 
                 114.88 
                 66.20 
                 80.49 
               
               
                   
                 HT29 
                 104.27 
                 99.44 
                 94.89 
               
               
                   
                 KM12 
                 111.92 
                 66.82 
                 94.44 
               
               
                   
                 SW-620 
                 98.29 
                 96.25 
                 96.35 
               
               
                 CNS Cancer 
                 SF-268 
                 117.27 
                 97.27 
                 100.26 
               
               
                   
                 SF-295 
                 92.80 
                 95.71 
                 93.22 
               
               
                   
                 SF-539 
                 110.08 
                 92.08 
                 87.80 
               
               
                   
                 SNB-19 
                 101.30 
                 95.95 
                 104.19 
               
               
                   
                 SNB-75 
                 82.91 
                 79.70 
                 69.12 
               
               
                   
                 U251 
                 100.63 
                 96.03 
                 98.98 
               
               
                 Melanoma 
                 LOX IMVI 
                 84.23 
                 93.40 
                 85.45 
               
               
                   
                 MALME-3M 
                 102.06 
                 114.83 
                 111.50 
               
               
                   
                 M14 
                 109.79 
                 112.68 
                 113.63 
               
               
                   
                 MDA-MB-435 
                 100.46 
                 107.24 
                 97.33 
               
               
                   
                 SK-MEL-2 
                 117.11 
                 N.T. 
                 95.09 
               
               
                   
                 SK-MEL-28 
                 90.08 
                 114.89 
                 113.43 
               
               
                   
                 SK-MEL-5 
                 86.30 
                 80.96 
                 94.89 
               
               
                   
                 UACC-257 
                 127.99 
                 107.69 
                 101.11 
               
               
                   
                 UACC-62 
                 94.45 
                 77.41 
                 78.16 
               
               
                 Ovarian Cancer 
                 IGROV1 
                 92.82 
                 54.41 
                 83.38 
               
               
                   
                 OVCAR-3 
                 119.93 
                 84.91 
                 103.48 
               
               
                   
                 OVCAR-4 
                 94.13 
                 72.83 
                 84.28 
               
               
                   
                 OVCAR-5 
                 137.00 
                 81.54 
                 89.14 
               
               
                   
                 OVCAR-8 
                 101.08 
                 94.33 
                 84.55 
               
               
                   
                 NCI/ADR-RES 
                 96.78 
                 92.22 
                 92.57 
               
               
                   
                 SK-OV-3 
                 N.T. 
                 92.62 
                 99.12 
               
               
                 Renal Cancer 
                 786-0 
                 112.40 
                 103.34 
                 108.01 
               
               
                   
                 A498 
                 N.T. 
                 82.03 
                 96.00 
               
               
                   
                 ACHN 
                 111.67 
                 88.46 
                 87.55 
               
               
                   
                 CAKI-1 
                 75.67 
                 73.84 
                 84.65 
               
               
                   
                 RXF 393 
                 112.80 
                 97.15 
                 101.32 
               
               
                   
                 SN12C 
                 88.03 
                 94.82 
                 95.38 
               
               
                   
                 TK-10 
                 138.45 
                 65.31 
                 91.84 
               
               
                   
                 UO-31 
                 80.62 
                 56.91 
                 48.63 
               
               
                 Prostate Cancer 
                 PC-3 
                 92.73 
                 89.44 
                 82.55 
               
               
                   
                 DU-145 
                 113.91 
                 106.88 
                 106.50 
               
               
                 Breast Cancer  
                 MCF7 
                 74.25 
                 5.24 
                 23.99 
               
               
                   
                 MDA-MB-231/ 
                 87.66 
                 83.87 
                 76.68 
               
               
                   
                 ATCC 
                   
                   
                   
               
               
                   
                 HS 578T 
                 91.01 
                 85.28 
                 72.84 
               
               
                   
                 BT-549 
                 119.62 
                 101.88 
                 102.55 
               
               
                   
                 T-47D 
                 86.97 
                 23.53 
                 44.88 
               
               
                   
                 MDA-MB-468 
                 107.92 
                 -31.61 
                 0.60 
               
               
                 Mean 
                   
                 98.17 
                 84.15 
                 87.15 
               
               
                 Delta 
                   
                 33.31 
                 115.76 
                 86.55 
               
               
                 Range 
                   
                 73.59 
                 146.5 
                 113.03 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 SJ-3, SJ-6 and SJ-8 data collected from NCI 
               
             
          
           
               
                   
                   
                 SJ-3 
                 SJ-6 
                 SJ-8 
               
               
                 Compound No. 
                   
                 NSC 
                 NSC 
                 NSC 
               
               
                 NCI No. 
                   
                 772864 
                 772860 
                 771782 
               
               
                   
               
             
          
           
               
                 Leukemia 
                 CCRF-CEM 
                 42.00 
                 104.33 
                 88.85 
               
               
                   
                 HL-60 (TB) 
                 94.33 
                 98.84 
                 97.09 
               
               
                   
                 K-562 
                 45.29 
                 103.57 
                 89.01 
               
               
                   
                 MOLT-4 
                 34.63 
                 94.41 
                 88.74 
               
               
                   
                 RPMI- 8226 
                 81.94 
                 97.99 
                 83.40 
               
               
                   
                 SR 
                 46.92 
                 98.51 
                 85.94 
               
               
                 Non-Small Cell 
                 A549/ATCC 
                 51.79 
                 101.69 
                 101.47 
               
               
                 Lung Cancer 
                 EKVX 
                 N.T. 
                 N.T. 
                 N.T. 
               
               
                   
                 HOP-62 
                 24.86 
                 64.18 
                 78.71 
               
               
                   
                 HOP-92 
                 N.T. 
                 N.T. 
                 66.08 
               
               
                   
                 NCI-H226 
                 80.86 
                 94.59 
                 87.21 
               
               
                   
                 NCI-H23 
                 80.63 
                 90.42 
                 90.40 
               
               
                   
                 NCI-H322M 
                 69.83 
                 107.08 
                 91.28 
               
               
                   
                 NCI-H460 
                 25.15 
                 101.21 
                 102.14 
               
               
                   
                 NCI-H522 
                 77.39 
                 98.45 
                 91.11 
               
               
                 Colon Cancer 
                 COLO 205 
                 45.69 
                 104.79 
                 100.71 
               
               
                   
                 HCC-2998 
                 88.65 
                 102.76 
                 107.23 
               
               
                   
                 HCT-116 
                 36.96 
                 102.51 
                 93.64 
               
               
                   
                 HCT-15 
                 50.38 
                 97.78 
                 80.29 
               
               
                   
                 HT29 
                 9.75 
                 104.84 
                 91.34 
               
               
                   
                 KM12 
                 53.42 
                 94.80 
                 109.99 
               
               
                   
                 SW-620 
                 43.72 
                 88.89 
                 103.71 
               
               
                 CNS Cancer 
                 SF-268 
                 65.88 
                 96.49 
                 103.58 
               
               
                   
                 SF-295 
                 N.T. 
                 96.18 
                 102.43 
               
               
                   
                 SF-539 
                 85.04 
                 90.22 
                 96.24 
               
               
                   
                 SNB-19 
                 94.02 
                 103.87 
                 100.01 
               
               
                   
                 SNB-75 
                 71.52 
                 84.42 
                 81.55 
               
               
                   
                 U251 
                 N.T. 
                 N.T. 
                 95.72 
               
               
                 Melanoma 
                 LOX IMVI 
                 N.T. 
                 N.T. 
                 91.20 
               
               
                   
                 MALME-3M 
                 52.55 
                 98.31 
                 136.93 
               
               
                   
                 M14 
                 76.44 
                 96.60 
                 106.99 
               
               
                   
                 MDA-MB-435 
                 92.72 
                 104.53 
                 106.62 
               
               
                   
                 SK-MEL-2 
                 N.T. 
                 N.T. 
                 104.29 
               
               
                   
                 SK-MEL-28 
                 87.40 
                 105.21 
                 113.81 
               
               
                   
                 5K-MEL-5 
                 82.51 
                 98.52 
                 99.19 
               
               
                   
                 UACC-257 
                 92.18 
                 106.47 
                 103.31 
               
               
                   
                 UACC-62 
                 99.56 
                 93.36 
                 88.33 
               
               
                 Ovarian Cancer 
                 IGROV1 
                 43.43 
                 94.36 
                 86.47 
               
               
                   
                 OVCAR-3 
                 73.13 
                 97.59 
                 102.34 
               
               
                   
                 OVCAR-4 
                 52.50 
                 97.11 
                 96.67 
               
               
                   
                 OVCAR-5 
                 89.34 
                 104.92 
                 90.30 
               
               
                   
                 OVCAR-8 
                 61.36 
                 96.38 
                 95.25 
               
               
                   
                 NCI/ADR-RES 
                 69.55 
                 90.28 
                 94.32 
               
               
                   
                 SK-OV-3 
                 84.20 
                 99.78 
                 107.26 
               
               
                 Renal Cancer 
                 786-0 
                 74.13 
                 102.73 
                 103.71 
               
               
                   
                 A498 
                 88.98 
                 87.55 
                 93.88 
               
               
                   
                 ACHN 
                 55.86 
                 94.75 
                 81.66 
               
               
                   
                 CAKI-1 
                 64.35 
                 83.89 
                 94.99 
               
               
                   
                 RXF 393 
                 51.90 
                 97.51 
                 114.61 
               
               
                   
                 SN12C 
                 61.60 
                 99.08 
                 96.95 
               
               
                   
                 TK-10 
                 95.55 
                 134.79 
                 101.98 
               
               
                   
                 UO-31 
                 25.86 
                 76.25 
                 45.74 
               
               
                 Prostate Cancer 
                 PC-3 
                 41.01 
                 90.64 
                 79.64 
               
               
                   
                 DU-145 
                 65.48 
                 103.47 
                 119.02 
               
               
                 Breast Cancer 
                 MCF7 
                 12.70 
                 64.65 
                 52.31 
               
               
                   
                 MDA-MB-231/ 
                 25.16 
                 90.96 
                 79.28 
               
               
                   
                 ATCC 
                   
                   
                   
               
               
                   
                 HS 578T 
                 84.70 
                 98.38 
                 88.93 
               
               
                   
                 BT-549 
                 87.48 
                 95.52 
                 93.95 
               
               
                   
                 T-47D 
                 43.28 
                 67.68 
                 88.81 
               
               
                   
                 MDA-MB-468 
                 33.81 
                 97.12 
                 59.47 
               
               
                 Mean 
                   
                 62.4 
                 96.2 
                 93.66 
               
               
                 Delta 
                   
                 52.65 
                 32.02 
                 47.92 
               
               
                 Range 
                   
                 89.81 
                 70.61 
                 91.19 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 SJ-9, SJ-10 and SJ-12 data collected from NCI 
               
             
          
           
               
                   
                   
                 SJ-9 
                 SJ-10 
                 SJ-12 
               
               
                 Compound No. 
                   
                 NSC 
                 NSC 
                 NSC 
               
               
                 NCI No. 
                   
                 772857 
                 772862 
                 771783 
               
               
                   
               
             
          
           
               
                 Leukemia 
                 CCRF-CEM 
                 105.04 
                 -35.45 
                 92.44 
               
               
                   
                 HL-60 (TB) 
                 94.50 
                 -38.36 
                 101.15 
               
               
                   
                 K-562 
                 100.89 
                 -65.71 
                 92.13 
               
               
                   
                 MOLT-4 
                 93.29 
                 -43.22 
                 92.90 
               
               
                   
                 RPMI-8226 
                 95.20 
                 -43.57 
                 85.92 
               
               
                   
                 SR 
                 99.53 
                 -55.19 
                 75.13 
               
               
                 Non-Small Cell 
                 A549/ATCC 
                 104.35 
                 18.70 
                 96.43 
               
               
                 Lung Cancer 
                 EKVX 
                 N.T. 
                 N.T. 
                 N.T. 
               
               
                   
                 HOP-62 
                 78.17 
                 -61.80 
                 61.42 
               
               
                   
                 HOP-92 
                 N.T. 
                 N.T. 
                 38.50 
               
               
                   
                 NCI-H226 
                 94.22 
                 49.94 
                 86.17 
               
               
                   
                 NCI-H23 
                 94.33 
                 49.19 
                 86.27 
               
               
                   
                 NCI-H322M 
                 92.29 
                 35.89 
                 87.41 
               
               
                   
                 NCI-H460 
                 93.32 
                 -66.36 
                 91.83 
               
               
                   
                 NCI-H522 
                 92.76 
                 18.08 
                 96.62 
               
               
                 Colon Cancer 
                 COLO 205 
                 96.30 
                 -81.49 
                 93.65 
               
               
                   
                 HCC-2998 
                 103.16 
                 -55.83 
                 103.21 
               
               
                   
                 HCT-116 
                 89.08 
                 -83.19 
                 92.78 
               
               
                   
                 HCT-15 
                 97.88 
                 -78.92 
                 92.83 
               
               
                   
                 HT29 
                 95.52 
                 -80.89 
                 93.76 
               
               
                   
                 KM12 
                 97.97 
                 -47.09 
                 99.06 
               
               
                   
                 SW-620 
                 91.88 
                 -73.67 
                 92.76 
               
               
                 CNS Cancer 
                 SF-268 
                 96.13 
                 34.33 
                 92.35 
               
               
                   
                 SF-295 
                 93.33 
                 23.75 
                 90.01 
               
               
                   
                 SF-539 
                 92.93 
                 36.91 
                 95.23 
               
               
                   
                 SNB-19 
                 113.43 
                 67.25 
                 85.41 
               
               
                   
                 SNB-75 
                 72.13 
                 22.34 
                 70.00 
               
               
                   
                 U251 
                 111.96 
                 N.T. 
                 85.86 
               
               
                 Melanoma 
                 LOX IMVI 
                 100.04 
                 N.T. 
                 87.17 
               
               
                   
                 MALME-3M 
                 101.05 
                 -32.28 
                 106.59 
               
               
                   
                 M14 
                 101.69 
                 -56.24 
                 106.31 
               
               
                   
                 MDA-MB-435 
                 107.70 
                 -6.57 
                 98.43 
               
               
                   
                 SK-MEL-2 
                 N.T. 
                 N.T. 
                 104.36 
               
               
                   
                 SK-MEL-28 
                 110.84 
                 -91.38 
                 110.81 
               
               
                   
                 SK-MEL-5 
                 89.52 
                 59.18 
                 97.67 
               
               
                   
                 UACC-257 
                 107.44 
                 -39.24 
                 95.34 
               
               
                   
                 UACC-62 
                 94.90 
                 -81.71 
                 96.67 
               
               
                 Ovarian Cancer 
                 IGROV1 
                 72.45 
                 3.23 
                 75.03 
               
               
                   
                 OVCAR-3 
                 96.58 
                 22.86 
                 93.41 
               
               
                   
                 OVCAR-4 
                 98.19 
                 35.59 
                 94.70 
               
               
                   
                 OVCAR-5 
                 94.37 
                 39.14 
                 99.31 
               
               
                   
                 OVCAR-8 
                 96.11 
                 -46.09 
                 87.51 
               
               
                   
                 NCI/ADR-RES 
                 102.85 
                 -4.00 
                 88.19 
               
               
                   
                 SK-OV-3 
                 84.60 
                 57.81 
                 87.98 
               
               
                 Renal Cancer 
                 786-0 
                 99.53 
                 25.31 
                 89.51 
               
               
                   
                 A498 
                 99.15 
                 59.79 
                 72.81 
               
               
                   
                 ACHN 
                 86.42 
                 -83.29 
                 88.10 
               
               
                   
                 CAKI-1 
                 82.68 
                 17.84 
                 83.81 
               
               
                   
                 RXF 393 
                 106.09 
                 20.51 
                 94.00 
               
               
                   
                 SN12C 
                 93.10 
                 15.89 
                 83.57 
               
               
                   
                 TK-10 
                 121.79 
                 47.07 
                 99.56 
               
               
                   
                 UO-31 
                 65.33 
                 -40.61 
                 47.60 
               
               
                 Prostate Cancer 
                 PC-3 
                 87.77 
                 -58.51 
                 82.93 
               
               
                   
                 DU-145 
                 106.04 
                 -41.83 
                 102.37 
               
               
                 Breast Cancer 
                 MCF7 
                 49.61 
                 -100.00 
                 68.30 
               
               
                   
                 MDA-MB-231/ 
                 93.08 
                 -10.45 
                 62.53 
               
               
                   
                 ATCC 
                   
                   
                   
               
               
                   
                 HS 578T 
                 87.68 
                 60.88 
                 70.47 
               
               
                   
                 BT-549 
                 92.91 
                 58.35 
                 82.89 
               
               
                   
                 T-47D 
                 83.86 
                 -31.54 
                 76.27 
               
               
                   
                 MDA-MB-468 
                 97.71 
                 -35.66 
                 95.71 
               
               
                 Mean 
                   
                 94.75 
                 -14.37 
                 88.15 
               
               
                 Delta 
                   
                 45.14 
                 85.63 
                 49.65 
               
               
                 Range 
                   
                 72.18 
                 167.25 
                 72.31 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 SJ-14, SJ-16 and SJ-20 data collected from NCI 
               
             
          
           
               
                   
                   
                 SJ-14 
                 SJ-16 
                 SJ-20 
               
               
                 Compound No. 
                   
                 NSC  
                 NSC 
                 NSC  
               
               
                 NCI No. 
                   
                 772859 
                 7772861 
                 772863 
               
               
                   
               
             
          
           
               
                 Leukemia 
                 CCRF-CEM 
                 95.17 
                 93.52 
                 93.78 
               
               
                   
                 HL-60 (TB) 
                 103.04 
                 105.45 
                 99.09 
               
               
                   
                 K-562 
                 99.26 
                 95.17 
                 94.25 
               
               
                   
                 MOLT-4 
                 98.39 
                 98.13 
                 95.46 
               
               
                   
                 RPMI-8226 
                 94.89 
                 95.33 
                 93.63 
               
               
                   
                 SR 
                 97.09 
                 95.93 
                 95.05 
               
               
                 Non-Small Cell 
                 A549/ATCC 
                 101.56 
                 90.89 
                 101.22 
               
               
                 Lung Cancer 
                 EKVX 
                 N.T. 
                 N.T. 
                 N.T. 
               
               
                   
                 HOP-62 
                 108.83 
                 N.T. 
                 90.22 
               
               
                   
                 HOP-92 
                 N.T. 
                 N.T. 
                 N.T. 
               
               
                   
                 NCI-H226 
                 92.80 
                 79.43 
                 89.19 
               
               
                   
                 NCI-H23 
                 92.80 
                 83.34 
                 87.22 
               
               
                   
                 NCI-H322M 
                 98.50 
                 98.63 
                 91.93 
               
               
                   
                 NCI-H460 
                 101.46 
                 97.04 
                 101.76 
               
               
                   
                 NCI-H522 
                 98.72 
                 80.10 
                 79.75 
               
               
                 Colon Cancer 
                 COLO 205 
                 104.54 
                 102.19 
                 106.63 
               
               
                   
                 HCC-2998 
                 106.04 
                 106.23 
                 105.79 
               
               
                   
                 HCT-116 
                 91.34 
                 78.18 
                 93.02 
               
               
                   
                 HCT-15 
                 89.64 
                 80.71 
                 100.39 
               
               
                   
                 HT29 
                 93.22 
                 82.40 
                 95.93 
               
               
                   
                 KM12 
                 99.33 
                 98.34 
                 105.95 
               
               
                   
                 SW-620 
                 93.06 
                 93.14 
                 91.16 
               
               
                 CNS Cancer 
                 SF-268 
                 96.39 
                 85.45 
                 83.89 
               
               
                   
                 SF-295 
                 96.87 
                 60.91 
                 90.05 
               
               
                   
                 SF-539 
                 101.34 
                 83.17 
                 83.97 
               
               
                   
                 SNB-19 
                 95.06 
                 88.40 
                 105.27 
               
               
                   
                 SNB-75 
                 86.36 
                 33.20 
                 37.76 
               
               
                   
                 U251 
                 N.T. 
                 N.T. 
                 N.T. 
               
               
                 Melanoma 
                 LOX IMVI 
                 N.T. 
                 N.T. 
                 N.T. 
               
               
                   
                 MALME-3M 
                 92.48 
                 100.05 
                 92.79 
               
               
                   
                 M14 
                 105.34 
                 97.52 
                 105.07 
               
               
                   
                 MDA-MB-435 
                 99.93 
                 99.55 
                 100.75 
               
               
                   
                 SK-MEL-2 
                 N.T. 
                 N.T. 
                 N.T. 
               
               
                   
                 SK-MEL-28 
                 107.58 
                 104.82 
                 103.93 
               
               
                   
                 5K-MEL-5 
                 97.48 
                 99.23 
                 96.87 
               
               
                   
                 UACC-257 
                 98.37 
                 98.40 
                 93.79 
               
               
                   
                 UACC-62 
                 95.06 
                 87.17 
                 86.44 
               
               
                 Ovarian Cancer 
                 IGROV1 
                 85.84 
                 65.13 
                 80.87 
               
               
                   
                 OVCAR-3 
                 99.54 
                 98.07 
                 104.27 
               
               
                   
                 OVCAR-4 
                 94.20 
                 90.32 
                 87.08 
               
               
                   
                 OVCAR-5 
                 106.41 
                 88.56 
                 98.22 
               
               
                   
                 OVCAR- 8 
                 96.55 
                 75.82 
                 83.98 
               
               
                   
                 NCI/ADR-RPS 
                 100.39 
                 97.88 
                 92.82 
               
               
                   
                 SK-OV-3 
                 96.85 
                 78.58 
                 86.02 
               
               
                 Renal Cancer 
                 786-0 
                 97.90 
                 81.41 
                 81.67 
               
               
                   
                 A498 
                 88.64 
                 97.48 
                 104.53 
               
               
                   
                 ACHN 
                 100.03 
                 68.58 
                 93.51 
               
               
                   
                 CAKI-1 
                 93.83 
                 80.23 
                 86.59 
               
               
                   
                 RXF 393 
                 95.60 
                 72.95 
                 78.38 
               
               
                   
                 SN12C 
                 99.08 
                 87.90 
                 88.17 
               
               
                   
                 TK-10 
                 N.T. 
                 115.61 
                 133.34 
               
               
                   
                 UO-31 
                 72.57 
                 65.02 
                 86.64 
               
               
                 Prostate Cancer 
                 PC-3 
                 86.19 
                 79.79 
                 72.83 
               
               
                   
                 DU-145 
                 110.73 
                 102.96 
                 98.98 
               
               
                 Breast Cancer 
                 MCF7 
                 75.18 
                 53.31 
                 77.46 
               
               
                   
                 MDA-MB-231/ 
                 82.96 
                 73.80 
                 79.81 
               
               
                   
                 ATCC 
                   
                   
                   
               
               
                   
                 HS 578T 
                 99.40 
                 N.T. 
                 71.75 
               
               
                   
                 BT-549 
                 102.74 
                 89.83 
                 101.57 
               
               
                   
                 T-47D 
                 92.20 
                 75.93 
                 86.68 
               
               
                   
                 MDA-MB-468 
                 103.99 
                 95.37 
                 101.04 
               
               
                 Mean 
                   
                 96.53 
                 87.29 
                 92.15 
               
               
                 Delta 
                   
                 23.96 
                 54.09 
                 54.39 
               
               
                 Range 
                   
                 38.16 
                 82.41 
                 95.58 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 SJ-23 data collected from NCI 
               
             
          
           
               
                   
                   
                   
                 SJ-23 
               
               
                   
                 Compound No. 
                   
                 NSC 
               
               
                   
                 NCI No. 
                   
                 772858 
               
               
                   
                   
               
             
          
           
               
                   
                 Leukemia 
                 CCRF-CEM 
                 109.87 
               
               
                   
                   
                 HL-60 (TB) 
                 109.78 
               
               
                   
                   
                 K-562 
                 95.70 
               
               
                   
                   
                 MOLT-4 
                 104.77 
               
               
                   
                   
                 RPMI-8226 
                 104.31 
               
               
                   
                   
                 SR 
                 105.15 
               
               
                   
                 Non-Small Cell 
                 A549/ATCC 
                 99.12 
               
               
                   
                 Lung Cancer 
                 EKVX 
                 N.T. 
               
               
                   
                   
                 HOP-62 
                 96.39 
               
               
                   
                   
                 HOP-92 
                 N.T. 
               
               
                   
                   
                 NCI-H226 
                 96.06 
               
               
                   
                   
                 NCI-H23 
                 95.41 
               
               
                   
                   
                 NCI-H322M 
                 94.59 
               
               
                   
                   
                 NCI-H460 
                 98.85 
               
               
                   
                   
                 NCI-H522 
                 99.28 
               
               
                   
                 Colon Cancer 
                 COLO 205 
                 98.52 
               
               
                   
                   
                 HCC-2998 
                 106.23 
               
               
                   
                   
                 HCT-116 
                 101.67 
               
               
                   
                   
                 HCT-15 
                 99.35 
               
               
                   
                   
                 HT29 
                 108.65 
               
               
                   
                   
                 KM12 
                 101.58 
               
               
                   
                   
                 SW-620 
                 92.51 
               
               
                   
                 CNS Cancer 
                 SF-268 
                 107.51 
               
               
                   
                   
                 SF-295 
                 97.83 
               
               
                   
                   
                 SF-539 
                 92.98 
               
               
                   
                   
                 SNB-19 
                 108.66 
               
               
                   
                   
                 SNB-75 
                 80.84 
               
               
                   
                   
                 U251 
                 98.15 
               
               
                   
                 Melanoma 
                 LOX IMVI 
                 103.19 
               
               
                   
                   
                 MALME-3M 
                 102.62 
               
               
                   
                   
                 M14 
                 101.18 
               
               
                   
                   
                 MDA-MB-435 
                 102.57 
               
               
                   
                   
                 SK-MEL-2 
                 N.T. 
               
               
                   
                   
                 SK-MEL-28 
                 107.03 
               
               
                   
                   
                 SK-MEL-5 
                 92.50 
               
               
                   
                   
                 UACC-257 
                 104.23 
               
               
                   
                   
                 UACC-62 
                 93.92 
               
               
                   
                 Ovarian Cancer 
                 IGROV1 
                 81.63 
               
               
                   
                   
                 OVCAR-3 
                 103.33 
               
               
                   
                   
                 OVCAR-4 
                 98.31 
               
               
                   
                   
                 OVCAR-5 
                 102.33 
               
               
                   
                   
                 OVCAR- 8 
                 104.73 
               
               
                   
                   
                 NCI/ADR-RES 
                 107.13 
               
               
                   
                   
                 SK-OV-3 
                 95.59 
               
               
                   
                 Renal Cancer 
                 786-0 
                 105.05 
               
               
                   
                   
                 A498 
                 104.44 
               
               
                   
                   
                 ACHN 
                 95.59 
               
               
                   
                   
                 CAKI-1 
                 90.50 
               
               
                   
                   
                 RXF 393 
                 107.22 
               
               
                   
                   
                 SN12C 
                 101.12 
               
               
                   
                   
                 TK-10 
                 131.97 
               
               
                   
                   
                 UO-31 
                 82.74 
               
               
                   
                 Prostate Cancer 
                 PC-3 
                 93.07 
               
               
                   
                   
                 DU-145 
                 114.04 
               
               
                   
                 Breast Cancer 
                 MCF7 
                 97.24 
               
               
                   
                   
                 MDA-MB-231/ATCC 
                 93.54 
               
               
                   
                   
                 HS 578T 
                 102.06 
               
               
                   
                   
                 BT-549 
                 105.34 
               
               
                   
                   
                 T-47D 
                 95.99 
               
               
                   
                   
                 MDA-MB-468 
                 106.42 
               
               
                   
                 Mean 
                   
                 100.53 
               
               
                   
                 Delta 
                   
                 19.69 
               
               
                   
                 Range 
                   
                 51.13 
               
               
                   
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 SJ-25, SJ-26 and SJ-27 data collected from NCI 
               
             
          
           
               
                   
                   
                 SJ-25 
                 SJ-26 
                 SJ-27 
               
               
                 Compound No. 
                   
                 NSC 
                 NSC 
                 NSC 
               
               
                 NCI No. 
                   
                 763971 
                 763970 
                 765596 
               
               
                   
               
             
          
           
               
                 Leukemia 
                 CCRF-CEM 
                 71.56 
                 105.78 
                 89.25 
               
               
                   
                 HL-60 (TB) 
                 91.75 
                 102.31 
                 108.77 
               
               
                   
                 K-562 
                 63.81 
                 97.48 
                 108.53 
               
               
                   
                 MOLT-4 
                 59.49 
                 95.10 
                 110.33 
               
               
                   
                 RPMI-8226 
                 62.28 
                 90.60 
                 90.30 
               
               
                   
                 SR 
                 61.70 
                 77.02 
                 N.T. 
               
               
                 Non-Small Cell 
                 A549/ATCC 
                 76.42 
                 104.88 
                 99.70 
               
               
                 Lung Cancer 
                 EKVX 
                 30.15 
                 72.14 
                 N.T. 
               
               
                   
                 HOP-62 
                 91.46 
                 91.26 
                 96.01 
               
               
                   
                 HOP-92 
                 N.T. 
                 N.T. 
                 77.75 
               
               
                   
                 NCI-H226 
                 80.52 
                 85.66 
                 89.22 
               
               
                   
                 NCI-H23 
                 66.22 
                 81.56 
                 93.26 
               
               
                   
                 NCI-H322M 
                 73.47 
                 90.72 
                 99.80 
               
               
                   
                 NCI-H460 
                 79.22 
                 83.32 
                 98.27 
               
               
                   
                 NCI-H522 
                 68.89 
                 92.22 
                 95.89 
               
               
                 Colon Cancer 
                 COLO 205 
                 87.39 
                 98.25 
                 108.91 
               
               
                   
                 HCC-2998 
                 96.27 
                 102.24 
                 104.46 
               
               
                   
                 HCT-116 
                 77.94 
                 103.43 
                 88.60 
               
               
                   
                 HCT-15 
                 80.10 
                 108.54 
                 94.98 
               
               
                   
                 HT29 
                 84.03 
                 102.38 
                 111.60 
               
               
                   
                 KM12 
                 84.62 
                 102.73 
                 98.35 
               
               
                   
                 SW-620 
                 86.99 
                 95.26 
                 98.89 
               
               
                 CNS Cancer 
                 SF-268 
                 96.53 
                 106.64 
                 113.64 
               
               
                   
                 SF-295 
                 73.28 
                 92.48 
                 N.T. 
               
               
                   
                 SF-539 
                 100.05 
                 105.79 
                 91.49 
               
               
                   
                 SNB-19 
                 89.19 
                 99.28 
                 96.35 
               
               
                   
                 SNB-75 
                 66.06 
                 80.33 
                 59.75 
               
               
                   
                 U251 
                 78.04 
                 96.46 
                 97.67 
               
               
                 Melanoma 
                 LOX IMVI 
                 68.41 
                 86.91 
                 116.91 
               
               
                   
                 MALME-3M 
                 107.23 
                 103.37 
                 107.54 
               
               
                   
                 M14 
                 98.89 
                 108.50 
                 96.50 
               
               
                   
                 MDA-MB-435 
                 95.15 
                 100.35 
                 100.31 
               
               
                   
                 SK-MEL-2 
                 95.85 
                 117.12 
                 109.44 
               
               
                   
                 SK-MEL-28 
                 86.90 
                 100.02 
                 106.24 
               
               
                   
                 SK-MEL-5 
                 68.56 
                 84.87 
                 98.51 
               
               
                   
                 UACC-257 
                 106.91 
                 106.31 
                 98.20 
               
               
                   
                 UACC-62 
                 84.47 
                 95.17 
                 74.08 
               
               
                 Ovarian Cancer 
                 IGROV1 
                 69.73 
                 91.28 
                 96.92 
               
               
                   
                 OVCAR-3 
                 89.42 
                 117.80 
                 111.89 
               
               
                   
                 OVCAR-4 
                 73.19 
                 80.74 
                 N.T. 
               
               
                   
                 OVCAR-5 
                 112.54 
                 126.77 
                 96.81 
               
               
                   
                 OVCAR-8 
                 90.21 
                 107.63 
                 98.75 
               
               
                   
                 NCPADR-RES 
                 73.58 
                 97.00 
                 94.29 
               
               
                   
                 SK-OV-3 
                 N.T. 
                 N.T. 
                 119.79 
               
               
                 Renal Cancer 
                 786-0 
                 100.58 
                 114.55 
                 103.51 
               
               
                   
                 A498 
                 N.T. 
                 N.T. 
                 93.51 
               
               
                   
                 ACHN 
                 88.12 
                 104.75 
                 90.83 
               
               
                   
                 CAKI-1 
                 41.86 
                 71.62 
                 90.65 
               
               
                   
                 RXF 393 
                 79.39 
                 99.93 
                 114.49 
               
               
                   
                 SN12C 
                 84.58 
                 96.69 
                 89.48 
               
               
                   
                 TK-10 
                 99.82 
                 126.63 
                 N.T. 
               
               
                   
                 UO-31 
                 56.23 
                 70.50 
                 55.69 
               
               
                 Prostate Cancer 
                 PC-3 
                 58.35 
                 93.44 
                 74.44 
               
               
                   
                 DU-145 
                 92.27 
                 111.80 
                 121.06 
               
               
                 Breast Cancer 
                 MCF7 
                 67.82 
                 68.09 
                 71.98 
               
               
                   
                 MDA-MB-231/ 
                 72.56 
                 86.98 
                 74.61 
               
               
                   
                 ATCC 
                   
                   
                   
               
               
                   
                 HS 578T 
                 58.28 
                 105.98 
                 92.74 
               
               
                   
                 BT-549 
                 92.88 
                 120.08 
                 92.95 
               
               
                   
                 T-47D 
                 63.89 
                 67.23 
                 78.97 
               
               
                   
                 MDA-MB-486 
                 77.36 
                 80.08 
                 99.51 
               
               
                 Mean 
                   
                 79.52 
                 96.60 
                 96.23 
               
               
                 delta 
                   
                 49.37 
                 29.37 
                 40.54 
               
               
                 Range 
                   
                 82.39 
                 59.54 
                 65.37 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
             
           
               
                 TABLE 9 
               
             
             
               
                   
               
               
                 The GI 50 , TGI and LC 50  data of TC-XCI, SJ-3  
               
               
                 and SJ-10 collected from NCI 
               
             
          
           
               
                   
                 (TC-XC1) (NSC763972) 
                 SJ-3 (NSC772864) 
                 SJ-10 (NSC772862) 
               
             
          
           
               
                 Panel/ 
                   
                 TGI 
                 LC 50   
                   
                 TGI 
                 LC 50   
                   
                 TGI 
                 LC 50   
               
               
                 Cell  
                   
                 Sub- 
                 Se- 
                   
                 Sub- 
                 Se- 
                   
                 Sub- 
                 Se- 
               
               
                 line 
                   
                 panel 
                 lectivity 
                   
                 panel 
                 lectivity 
                   
                 panel 
                 lectivity 
               
               
                 (μM) 
                 GI 50   
                 MID b   
                 ratio 
                 GI 50   
                 MID b   
                 ratio 
                 GI 50   
                 MID b   
                 ratio 
               
               
                   
               
             
          
           
               
                 Leukemia 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
             
          
           
               
                 CCRF-CEM 
                 1.42 
                 1.114 
                 8.063 
                 15.5 
                 &gt;100 
                 8.24 
                 9.696 
                 1.475 
                 3.50 
                 7.80 
                 6.32 
                 11.000 
                 0.954 
                 &gt;100 
                 &gt;100 
               
               
                 HL-60(TB) 
                 1.06 
                   
                   
                 4.28 
                 &gt;100 
                 N.T. 
                   
                   
                 N.T. 
                 N.T. 
                 36.9 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 K-562 
                 0.315 
                   
                   
                 &gt;100 
                 &gt;100 
                 8.75 
                   
                   
                 3.61 
                 7.46 
                 7.80 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 MOLT-4 
                 1.97 
                   
                   
                 15.3 
                 &gt;100 
                 6.24 
                   
                   
                 3.43 
                 7.91 
                 4.41 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 RPMI-8226 
                 0.549 
                   
                   
                 &gt;100 
                 &gt;100 
                 20.20 
                   
                   
                 4.31 
                 9.73 
                 7.48 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SR 
                 1.37 
                   
                   
                 43.4 
                 &gt;100 
                 5.05 
                   
                   
                 4.06 
                 11.60 
                 3.09 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 Non-Small Cell 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Lung Cancer 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 A549/ATCC 
                 2.95 
                 5.840 
                 1.538 
                 &gt;100 
                 &gt;100 
                 15.20 
                 11.819 
                 1.210 
                 3.51 
                 6.72 
                 4.87 
                 6.477 
                 1.621 
                 &gt;100 
                 &gt;100 
               
               
                 EKVX 
                 N.T. 
                   
                   
                 N.T. 
                 N.T. 
                 N.T. 
                   
                   
                 N.T. 
                 N.T. 
                 N.T. 
                   
                   
                 N.T. 
                 N.T. 
               
               
                 HOP-62 
                 3.84 
                   
                   
                 &gt;100 
                 &gt;100 
                 4.51 
                   
                   
                 2.83 
                 5.74 
                 12.3 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 HOP-92 
                 1.21 
                   
                   
                 13.4 
                 &gt;100 
                 3.08 
                   
                   
                 5.80 
                 25.10 
                 N.T. 
                   
                   
                 N.T. 
                 N.T. 
               
               
                 NCI-H226 
                 11.6 
                   
                   
                 &gt;100 
                 &gt;100 
                 1.88 
                   
                   
                 — 
                 — 
                 7.77 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 NCI-H23 
                 3.44 
                   
                   
                 63.6 
                 &gt;100 
                 2.63 
                   
                   
                 4.00 
                 8.35 
                 6.65 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 NCI-H322M 
                 16 
                   
                   
                 92.3 
                 &gt;100 
                 34.50 
                   
                   
                 13.10 
                 36.20 
                 5.62 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 NCI-460 
                 7.44 
                   
                   
                 86.3 
                 &gt;100 
                 5.15 
                   
                   
                 3.20 
                 6.74 
                 4.15 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 NCI-H522 
                 0.238 
                   
                   
                 0.644 
                 3.57 
                 27.60 
                   
                   
                 3.80 
                 7.23 
                 3.98 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 Colon Cancer 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 COLO 205 
                 3.77 
                 9.560 
                 0.939 
                 15.8 
                 39.8 
                 2.41 
                 18.400 
                 0.778 
                 — 
                 — 
                 12.2 
                 9.763 
                 1.075 
                 &gt;100 
                 &gt;100 
               
               
                 HCC-2998 
                 11.0 
                   
                   
                 &gt;100 
                 &gt;100 
                 &gt;100 
                   
                   
                 4.08 
                 7.94 
                 30.9 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 HCT-116 
                 0.807 
                   
                   
                 &gt;100 
                 &gt;100 
                 6.19 
                   
                   
                 3.19 
                 6.06 
                 5.42 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 HCT-15 
                 0.716 
                   
                   
                 &gt;100 
                 &gt;100 
                 4.37 
                   
                   
                 3.51 
                 7.50 
                 4.34 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 HT29 
                 39.0 
                   
                   
                 &gt;100 
                 &gt;100 
                 4.23 
                   
                   
                 3.16 
                 6.28 
                 7.84 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 KM12 
                 4.62 
                   
                   
                 &gt;100 
                 &gt;100 
                 6.48 
                   
                   
                 3.11 
                 5.96 
                 2.50 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SW-620 
                 7.01 
                   
                   
                 &gt;100 
                 &gt;100 
                 5.12 
                   
                   
                 3.06 
                 6.67 
                 5.14 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 CNS Cancer 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 SF-268 
                 4.28 
                 14.364 
                 0.625 
                 &gt;100 
                 &gt;100 
                 17.70 
                 14.875 
                 0.962 
                 3.27 
                 6.52 
                 8.71 
                 8.053 
                 1.304 
                 &gt;100 
                 &gt;100 
               
               
                 SF-295 
                 10.8 
                   
                   
                 87.9 
                 &gt;100 
                 17.80 
                   
                   
                 4.60 
                 9.85 
                 7.79 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SF-539 
                 23.1 
                   
                   
                 64.2 
                 &gt;100 
                 20.90 
                   
                   
                 3.15 
                 5.86 
                 14.2 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SNB-19 
                 30.9 
                   
                   
                 &gt;100 
                 &gt;100 
                 18.20 
                   
                   
                 3.42 
                 — 
                 8.27 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SNB-75 
                 N.T. 
                   
                   
                 N.T. 
                 &gt;100 
                 3.25 
                   
                   
                 2.35 
                 4.86 
                 4.53 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 U251 
                 2.74 
                   
                   
                 &gt;100 
                 &gt;100 
                 11.40 
                   
                   
                 3.06 
                 5.88 
                 4.82 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 Melanoma 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 LOX IMV1 
                 0.64 
                 10.637 
                 0.844 
                 57.00 
                 &gt;100 
                 6.04 
                 15.654 
                 0.914 
                 3.04 
                 6.02 
                 4.74 
                 19.894 
                 0.528 
                 &gt;100 
                 &gt;100 
               
               
                 MALME-3M 
                 8.32 
                   
                   
                 42.20 
                 &gt;100 
                 17.30 
                   
                   
                 3.83 
                 7.46 
                 8.87 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 M14 
                 3.75 
                   
                   
                 &gt;100 
                 &gt;100 
                 16.50 
                   
                   
                 5.48 
                 19.30 
                 7.49 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 MDA-MB-435 
                 3.97 
                   
                   
                 &gt;100 
                 &gt;100 
                 20.20 
                   
                   
                 3.86 
                 7.62 
                 7.01 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SK-MEL-2 
                 17.10 
                   
                   
                 50.20 
                 &gt;100 
                 37.70 
                   
                   
                 4.73 
                 10.40 
                 7.36 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SK-MEL-28 
                 33.00 
                   
                   
                 &gt;100 
                 &gt;100 
                 6.00 
                   
                   
                 3.21 
                 5.83 
                 &gt;100 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SK-MEL-5 
                 7.36 
                   
                   
                 22.50 
                 56.5 
                 1.15 
                   
                   
                 2.61 
                 — 
                 4.10 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 UACC-257 
                 6.39 
                   
                   
                 65.10 
                 &gt;100 
                 21.20 
                   
                   
                 3.39 
                 6.37 
                 35.1 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 UACC-62 
                 15.20 
                   
                   
                 88.40 
                 &gt;100 
                 14.80 
                   
                   
                 3.31 
                 6.68 
                 4.38 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 Ovarian Cancer 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 IGROV1 
                 14.3 
                 13.649 
                 0.658 
                 &gt;100 
                 &gt;100 
                 11.20 
                 17.448 
                 0.820 
                 3.62 
                 7.82 
                 5.94 
                 13.591 
                 0.772 
                 &gt;100 
                 &gt;100 
               
               
                 OVCAR-3 
                 4.46 
                   
                   
                 95.1 
                 &gt;100 
                 N.T. 
                   
                   
                 N.T. 
                 N.T. 
                 12.8 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 OVCAR-4 
                 8.83 
                   
                   
                 21.9 
                 49.30 
                 2.99 
                   
                   
                 2.79 
                 5.68 
                 6.39 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 OVCAR-5 
                 16.1 
                   
                   
                 66.1 
                 &gt;100 
                 21.50 
                   
                   
                 3.32 
                 6.52 
                 34.5 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 OVCAR-8 
                 1.49 
                   
                   
                 &gt;100 
                 &gt;100 
                 13.80 
                   
                   
                 3.63 
                 7.76 
                 8.66 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 NCI/ADR-RES 
                 2.26 
                   
                   
                 25.2 
                 &gt;100 
                 19.30 
                   
                   
                 3.67 
                 7.41 
                 22.5 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SK-OV-3 
                 48.1 
                   
                   
                 &gt;100 
                 &gt;100 
                 35.90 
                   
                   
                 5.57 
                 17.20 
                 4.35 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 Renal Cancer 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 786-O 
                 23.4 
                 10.988 
                 0.817 
                 &gt;100 
                 &gt;100 
                 26.80 
                 12.733 
                 1.124 
                 3.29 
                 6.01 
                 23.5 
                 6.370 
                 1.648 
                 &gt;100 
                 &gt;100 
               
               
                 A498 
                 6.75 
                   
                   
                 71.7 
                 &gt;100 
                 8.76 
                   
                   
                 1.78 
                 50.80 
                 2.63 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 ACHN 
                 4.2 
                   
                   
                 &gt;100 
                 &gt;100 
                 6.44 
                   
                   
                 3.04 
                 5.89 
                 3.14 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 CAKI-1 
                 7.92 
                   
                   
                 &gt;100 
                 &gt;100 
                 14.80 
                   
                   
                 3.26 
                 6.80 
                 2.52 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 RXF 393 
                 17.9 
                   
                   
                 63.6 
                 &gt;100 
                 N.T. 
                   
                   
                 N.T. 
                 N.T. 
                 4.55 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 SN12C 
                 3.24 
                   
                   
                 &gt;100 
                 &gt;100 
                 4.12 
                   
                   
                 2.87 
                 6.16 
                 5.42 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 TK-10 
                 22.7 
                   
                   
                 68.9 
                 &gt;100 
                 24.60 
                   
                   
                 3.70 
                 6.38 
                 N.T. 
                   
                   
                 N.T. 
                 N.T. 
               
               
                 UO-31 
                 1.79 
                   
                   
                 35.3 
                 &gt;100 
                 3.61 
                   
                   
                 2.88 
                 6.48 
                 2.83 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 Prostate Cancer 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 PC-3 
                 0.606 
                 2.968 
                 3.026 
                 &gt;100 
                 &gt;100 
                 12.50 
                 15.650 
                 0.914 
                 3.82 
                 8.98 
                 5.93 
                 5.360 
                 1.959 
                 &gt;100 
                 &gt;100 
               
               
                 DU-145 
                 5.33 
                   
                   
                 &gt;100 
                 &gt;100 
                 18.80 
                   
                   
                 2.94 
                 5.43 
                 4.79 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 Breast Cancer 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 MCF7 
                 7.73 
                 7.280 
                 1.234 
                 &gt;100 
                 &gt;100 
                 0.44 
                 12.345 
                 1.159 
                 2.60 
                 5.54 
                 5.42 
                 6.813 
                 1.541 
                 &gt;100 
                 &gt;100 
               
               
                 MDA-MB-231/ 
                 2.44 
                   
                   
                 13.8 
                 75.1 
                 2.23 
                   
                   
                 2.71 
                 5.70 
                 7.23 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 ATCC 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 HS 578T 
                 20.3 
                   
                   
                 &gt;100 
                 &gt;100 
                 19.30 
                   
                   
                 10.00 
                 46.10 
                 4.77 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 BT-549 
                 7.55 
                   
                   
                 &gt;100 
                 &gt;100 
                 32.50 
                   
                   
                 9.50 
                 45.50 
                 10.6 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 T-47D 
                 0.84 
                   
                   
                 2.86 
                 8.96 
                 17.80 
                   
                   
                 3.56 
                 7.19 
                 8.44 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 MDA-MB-468 
                 4.82 
                   
                   
                 29.4 
                 &gt;100 
                 1.71 
                   
                   
                 3.07 
                 — 
                 4.42 
                   
                   
                 &gt;100 
                 &gt;100 
               
               
                 MID a   
                 8.982 
                   
                   
                   
                   
                 14.306 
                   
                   
                   
                   
                 10.498 
                   
                   
                   
                   
               
               
                   
               
               
                 MID a   
               
               
                 MID a  = Average sensitivity of all cell line in μM. 
               
               
                 MID b  = Average sensitivity of all cell line of a particular subpanel in μM. 
               
               
                 Selectivity ratio = MID a :MID b   
               
               
                 N.T. = No test